Descriptor: "Neoplasm metastasis" / Journal: oncotarget - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Neoplasm metastasis"' showing total 1,879 results

Start Over Descriptor "Neoplasm metastasis" Journal oncotarget

1,879 results on '"Neoplasm metastasis"'

1. High competing risks minimize real-world utility of adjuvant targeted therapy in renal cell carcinoma: a population-based analysis

Author: Chandrasekar, Thenappan, Klaassen, Zachary, Goldberg, Hanan, Sayyid, Rashid K, Kulkarni, Girish S, and Fleshner, Neil E
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Kidney Disease, Rare Diseases, Patient Safety, Good Health and Well Being, carcinoma, renal cell, drug therapy, mortality, neoplasm metastasis, survival, Oncology and carcinogenesis
Abstract: ObjectiveTo utilize a population-based approach to address the role of adjuvant TT in the management of RCC.MethodsPatients with RCC (2006-2013) in the SEER database were stratified by metastatic disease at the time of diagnosis (cM0/cM1). cM0 patients following surgical excision were stratified into low and high-risk (ASSURE and S-TRAC criteria). Multivariable analyses performed to identify predictors of TT receipt; Fine and Gray competing risks analyses used to identify predictors of cancer-specific mortality (CSM). Subset analyses included patients with clear cell histology and high-risk cM0. Survival analyses were used to evaluate overall survival (OS) and cancer-specific survival (CSS) for all cohorts, stratified on TT receipt.Results79,926 patients included (71,682 cM0, 8,244 cM1); median follow-up for the entire cohort was 40.1 months. Of 31,453 patients with histologic grade data, 18,328 and 13,125 were low- and high-risk cM0, respectively. TT utilization in cM1 patients peaked at 50.6% and was associated with reduced CSM (HR 0.73, p
Published: 2018

2. Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer

Author: Rafii, Saeed, Gourley, Charlie, Kumar, Rajiv, Geuna, Elena, Ang, Joo Ern, Rye, Tzyvia, Chen, Lee-May, Shapira-Frommer, Ronnie, Friedlander, Michael, Matulonis, Ursula, De Greve, Jacques, Oza, Amit M, Banerjee, Susana, Molife, L Rhoda, Gore, Martin E, Kaye, Stan B, and Yap, Timothy A
Subjects: Rare Diseases, Orphan Drug, Cancer, Ovarian Cancer, Clinical Research, Genetics, Breast Cancer, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Aged, Antineoplastic Agents, BRCA1 Protein, BRCA2 Protein, Female, Germ-Line Mutation, Humans, Middle Aged, Neoplasm Grading, Neoplasm Metastasis, Neoplasm Staging, Ovarian Neoplasms, Phthalazines, Piperazines, Poly(ADP-ribose) Polymerase Inhibitors, Prognosis, Recurrence, Survival Analysis, Treatment Outcome, PARP inhibitor, olaparib, BRCA, ovarian cancer, predictive biomarkers, Oncology and Carcinogenesis
Abstract: BackgroundThe PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib.Results108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p
Published: 2017

3. A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in breast cancer

Author: Li, Chaoyang, Zhang, Pengju, Jiang, Anli, Mao, Jian-Hua, and Wei, Guangwei
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biotechnology, Lung, Cancer, Lung Cancer, Breast Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Animals, Antineoplastic Agents, Breast Neoplasms, Cell Cycle Checkpoints, Cell Line, Tumor, Cell Movement, Cell Proliferation, Disease Models, Animal, Female, Humans, Mice, Middle Aged, Neoplasm Grading, Neoplasm Metastasis, Neoplasm Proteins, Neoplasm Staging, Peptide Fragments, Tumor Suppressor Proteins, Xenograft Model Antitumor Assays, C2ORF40 mimic peptide, breast cancer, proliferation, xenograft, mitosis, Oncology and carcinogenesis
Abstract: C2ORF40 encodes a secreted protein which is cleaved to generate soluble peptides by proteolytic processing and this process is believed to be necessary for C2ORF40 to exert cell type specific biological activity. Here, we reported a short mimic peptide of human C2ORF40 acts potential therapeutic efficacy in human cancer cells in vitro and in vivo. We synthesized a short peptide of human C2ORF40, named C2ORF40 mimic peptide fragment and assessed its biological function on cancer cell growth, migration and tumorigenesis. Cell growth assay showed that C2ORF40 mimic peptide fragment significantly suppressed cell proliferation of breast and lung cancer cells. Moreover, C2ORF40 mimic peptide fragment significantly inhibited the migration and invasion of breast cancer cells. Furthermore, we showed that this peptide suppressed tumorigenesis in breast tumor xenograft model. Cell cycle assay indicated that the C2ORF40 mimic peptide fragment suppressed the growth of tumor cells through inducing mitotic phase arrest. In conclusion, our results firstly suggested that this short synthetic peptide of human C2ORF40 may be a candidate tumor therapeutic agent.
Published: 2017

4. Selective function-blocking monoclonal human antibody highlights the important role of membrane type-1 matrix metalloproteinase (MT1-MMP) in metastasis

Author: Remacle, Albert G, Cieplak, Piotr, Nam, Dong Hyun, Shiryaev, Sergey A, Ge, Xin, and Strongin, Alex Y
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biotechnology, Cancer, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Animals, Antibodies, Blocking, Antineoplastic Agents, Immunological, Binding, Competitive, Catalytic Domain, Cell Line, Tumor, Cell Movement, Cell Survival, Collagen, Disease Models, Animal, Enzyme Activation, Female, Heterografts, Humans, Immunoglobulin Fab Fragments, Matrix Metalloproteinase 14, Matrix Metalloproteinase Inhibitors, Mice, Models, Molecular, Molecular Conformation, Neoplasm Metastasis, Neoplasm Staging, Neoplasms, Protein Binding, Proteolysis, Recombinant Proteins, metastasis, cancer, MT1-MMP, antibody, proteinase, Oncology and carcinogenesis
Abstract: The invasion-promoting MT1-MMP is a cell surface-associated collagenase with a plethora of critical cellular functions. There is a consensus that MT1-MMP is a key protease in aberrant pericellular proteolysis in migrating cancer cells and, accordingly, a promising drug target. Because of high homology in the MMP family and a limited success in the design of selective small-molecule inhibitors, it became evident that the inhibitor specificity is required for selective and successful MT1-MMP therapies. Using the human Fab antibody library (over 1.25×109 individual variants) that exhibited the extended, 23-27 residue long, VH CDR-H3 segments, we isolated a panel of the inhibitory antibody fragments, from which the 3A2 Fab outperformed others as a specific and potent, low nanomolar range, inhibitor of MT1-MMP. Here, we report the in-depth characterization of the 3A2 antibody. Our multiple in vitro and cell-based tests and assays, and extensive structural modeling of the antibody/protease interactions suggest that the antibody epitope involves the residues proximal to the protease catalytic site and that, in contrast with tissue inhibitor-2 of MMPs (TIMP-2), the 3A2 Fab inactivates the protease functionality by binding to the catalytic domain outside the active site cavity. In agreement with the studies in metastasis by others, our animal studies in acute pulmonary melanoma metastasis support a key role of MT1-MMP in metastatic process. Conversely, the selective anti-MT1-MMP monotherapy significantly alleviated melanoma metastatic burden. It is likely that further affinity maturation of the 3A2 Fab will result in the lead inhibitor and a proof-of-concept for MT1-MMP targeting in metastatic cancers.
Published: 2017

5. Tumor-targeting adenovirus OBP-401 inhibits primary and metastatic tumor growth of triple-negative breast cancer in orthotopic nude-mouse models

Author: Yano, Shuya, Takehara, Kiyoto, Kishimoto, Hiroyuki, Tazawa, Hiroshi, Urata, Yasuo, Kagawa, Shunsuke, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Breast Cancer, 2.1 Biological and endogenous factors, Aetiology, Adenoviridae, Animals, Cell Line, Tumor, Disease Models, Animal, Female, Humans, Mammary Glands, Animal, Mice, Mice, Nude, Neoplasm Metastasis, Oncolytic Virotherapy, Organ Specificity, Telomerase, Triple Negative Breast Neoplasms, Xenograft Model Antitumor Assays, GFP, green fluorescent protein, RFP, red fluorescent protein, OBP-401, TNBC, adenovirus, high-metastatic, nude mouse, triple-negative breast cancer, variants, Oncology and carcinogenesis
Abstract: Our laboratory previously developed a highly-invasive, triple-negative breast cancer (TNBC) variant using serial orthotopic implantation of the human MDA-MB-231 cell line in nude mice. The isolated variant was highly-invasive in the mammary gland and lymphatic channels and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present study, the tumor-selective telomerase dependent OBP-401 adenovirus was injected intratumorally (i.t.) (1 × 108 PFU) when the high-metastatic MDA-MB-231 primary tumor expressing red fluorescent protein (MDA-MB-231-RFP) reached approximately 500 mm3 (diameter; 10 mm). The mock-infected orthotopic primary tumor grew rapidly. After i.t. OBP-401 injection, the growth of the orthotopic tumors was arrested. Six weeks after implantation, the fluorescent area and fluorescence intensity showed no increase from the beginning of treatment. OBP-401 was then injected into high-metastatic MDA-MB-231-RFP primary orthotopic tumor growing in mice which already had developed metastasis within lymphatic ducts. All 7 of 7 control mice subsequently developed lymph node metastasis. In contrast, none of 7 mice which received OBP-401 had lymph node metastasis. Seven of 7 control mice also had gross lung metastasis. In contrast, none of the 7 mice which received OBP-401 had gross lung metastasis. Confocal laser microscopy imaging demonstrated that all control mice had diffuse lung metastases. In contrast, all 7 mice which received OBP-401 only had a few metastatic cells in the lung. OBP-401 treatment significantly extended survival of the treated mice.
Published: 2016

6. Comprehensive adipocytic and neurogenic tissue microarray analysis of NY-ESO-1 expression - a promising immunotherapy target in malignant peripheral nerve sheath tumor and liposarcoma

Author: Shurell, Elizabeth, Vergara-Lluri, Maria E, Li, Yunfeng, Crompton, Joseph G, Singh, Arun, Bernthal, Nicholas, Wu, Hong, Eilber, Fritz C, and Dry, Sarah M
Subjects: Rare Diseases, Cancer, Neurofibromatosis, Neurosciences, Biotechnology, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Adipogenesis, Adipose Tissue, Antigens, Neoplasm, Biomarkers, Humans, Immunohistochemistry, Immunotherapy, Liposarcoma, Membrane Proteins, Neoplasm Metastasis, Neoplasm Recurrence, Local, Nerve Sheath Neoplasms, Nerve Tissue, Neurogenesis, Tissue Array Analysis, NY-ESO-1, sarcoma, MPNST, liposarcoma, immunotherapy, Oncology and Carcinogenesis
Abstract: BackgroundImmunotherapy targeting cancer-testis antigen NY-ESO-1 shows promise for tumors with poor response to chemoradiation. Malignant peripheral nerve sheath tumors (MPNSTs) and liposarcomas (LPS) are chemoresistant and have few effective treatment options. Materials Methods: Using a comprehensive tissue microarray (TMA) of both benign and malignant tumors in primary, recurrent, and metastatic samples, we examined NY-ESO-1 expression in peripheral nerve sheath tumor (PNST) and adipocytic tumors. The PNST TMA included 42 MPNSTs (spontaneous n = 26, NF1-associated n = 16), 35 neurofibromas (spontaneous n = 22, NF-1 associated n = 13), 11 schwannomas, and 18 normal nerves. The LPS TMA included 48 well-differentiated/dedifferentiated (WD/DD) LPS, 13 myxoid/round cell LPS, 3 pleomorphic LPS, 8 lipomas, 1 myelolipoma, and 3 normal adipocytic tissue samples. Stained in triplicate, NY-ESO-1 intensity and density were scored.ResultsNY-ESO-1 expression was exclusive to malignant tumors. 100% of myxoid/round cell LPS demonstrated NY-ESO-1 expression, while only 6% of WD/DD LPS showed protein expression, one of which was WD LPS. Of MPNST, 4/26 (15%) spontaneous and 2/16 (12%) NF1-associated MPNSTs demonstrated NY-ESO-1 expression. Strong NY-ESO-1 expression was observed in myxoid/round cell and dedifferentiated LPS, and MPNST in primary, neoadjuvant, and metastatic settings.ConclusionsWe found higher prevalence of NY-ESO-1 expression in MPNSTs than previously reported, highlighting a subset of MPNST patients who may benefit from immunotherapy. This study expands our understanding of NY-ESO-1 in WD/DD LPS and is the first demonstration of staining in a WD LPS and metastatic/recurrent myxoid/round cell LPS. These results suggest immunotherapy targeting NY-ESO-1 may benefit patients with aggressive tumors resistant to conventional therapy.
Published: 2016

7. Patient-derived mouse models of cancer need to be orthotopic in order to evaluate targeted anti-metastatic therapy

Author: Hiroshima, Yukihiko, Maawy, Ali, Zhang, Yong, Zhang, Nan, Murakami, Takashi, Chishima, Takashi, Tanaka, Kuniya, Ichikawa, Yasushi, Bouvet, Michael, Endo, Itaru, and Hoffman, Robert M
Subjects: Cancer, Rare Diseases, Good Health and Well Being, Animals, Benzamides, Disease Models, Animal, Female, Humans, Mice, Neoplasm Metastasis, Precision Medicine, Pyridines, Uterine Cervical Neoplasms, Xenograft Model Antitumor Assays, Patient-derived orthotopic xenograft, PDOX, cervical cancer, nude mouse, primary tumor, patient-derived orthotopic xenograft, Oncology and Carcinogenesis
Abstract: Patient-derived xenograft (PDX) mouse models of cancer are emerging as an important component of personalized precision cancer therapy. However, most models currently offered to patients have their tumors subcutaneously-transplanted in immunodeficient mice, which rarely metastasize. In contrast, orthotopic-transplant patient-derived models, termed patient-derived orthotopic xenografts (PDOX), usually metastasize as in the patient. We demonstrate in the present report why orthotopic models are so important for the patient, since primary and metastatic tumors developed in an orthotopic model can have differential chemosensitivity, not detectable in standard subcutaneous tumor models. A subcutaneous nude mouse model of HER-2 expressing cervical carcinoma was not sensitive to entinostat (a benzamide histone deactylase inhibitor), which also did not inhibit primary tumor growth in a PDOX model of the same tumor. However, in the PDOX model, entinostat alone significantly reduced the metastatic tumor burden, compared to the control. Thus, only the PDOX model could be used to discover the anti-metastatic activity of entinostat for this patient. The results of the present report indicate the importance of using mouse models that can recapitulate metastatic cancer for precisely individualizing cancer therapy.
Published: 2016

8. FOXC2 augments tumor propagation and metastasis in osteosarcoma

Author: Gozo, Maricel C, Jia, Dongyu, Aspuria, Paul-Joseph, Cheon, Dong-Joo, Miura, Naoyuki, Walts, Ann E, Karlan, Beth Y, and Orsulic, Sandra
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Rare Diseases, Stem Cell Research, Pediatric Research Initiative, Aetiology, 2.1 Biological and endogenous factors, Animals, Anoikis, Bone Neoplasms, Cell Adhesion, Cell Differentiation, Cell Line, Tumor, Cell Movement, Down-Regulation, Forkhead Transcription Factors, Gene Expression Regulation, Neoplastic, Gene Silencing, Humans, Lung Neoplasms, Mice, Mice, Nude, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasm Transplantation, Osteosarcoma, Receptors, CXCR4, Signal Transduction, anoikis, forkhead box C2, osteosarcoma, metastasis, invasion, Oncology and carcinogenesis
Abstract: Osteosarcoma is a highly malignant tumor that contains a small subpopulation of tumor-propagating cells (also known as tumor-initiating cells) characterized by drug resistance and high metastatic potential. The molecular mechanism by which tumor-propagating cells promote tumor growth is poorly understood. Here, we report that the transcription factor forkhead box C2 (FOXC2) is frequently expressed in human osteosarcomas and is important in maintaining osteosarcoma cells in a stem-like state. In osteosarcoma cell lines, we show that anoikis conditions stimulate FOXC2 expression. Downregulation of FOXC2 decreases anchorage-independent growth and invasion in vitro and lung metastasis in vivo, while overexpression of FOXC2 increases tumor propagation in vivo. In osteosarcoma cell lines, we demonstrate that high levels of FOXC2 are associated with and required for the expression of osteosarcoma tumor-propagating cell markers. In FOXC2 knockdown cell lines, we show that CXCR4, a downstream target of FOXC2, can restore osteosarcoma cell invasiveness and metastasis to the lung.
Published: 2016

9. Characterizing the immune microenvironment of malignant peripheral nerve sheath tumor by PD-L1 expression and presence of CD8+ tumor infiltrating lymphocytes

Author: Shurell, Elizabeth, Singh, Arun S, Crompton, Joseph G, Jensen, Sarah, Li, Yunfeng, Dry, Sarah, Nelson, Scott, Chmielowski, Bartosz, Bernthal, Nicholas, Federman, Noah, Tumeh, Paul, and Eilber, Fritz C
Subjects: Orphan Drug, Rare Diseases, Neurosciences, Neurofibromatosis, Cancer, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, B7-H1 Antigen, Biomarkers, Tumor, CD8-Positive T-Lymphocytes, Disease Progression, Humans, Immunohistochemistry, Lymphocytes, Tumor-Infiltrating, Neoplasm Metastasis, Neoplasm Recurrence, Local, Neurilemmoma, Proportional Hazards Models, Prospective Studies, Soft Tissue Neoplasms, Time Factors, Tissue Array Analysis, Treatment Outcome, Tumor Microenvironment, immune microenvironment, MPNST, PD-L1, CD8, sarcoma, Oncology and Carcinogenesis
Abstract: BackgroundMalignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with few treatment options. Tumor immune state has not been characterized in MPNST, and is important in determining response to immune checkpoint blockade. Our aim was to evaluate the expression of programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and presence of CD8+ tumor infiltrating lymphocytes (TILs) in MPNST, and correlate these findings with clinical behavior and outcome.ResultsPD-L1 staining of at least 1% was seen in 0/20 nerves, 2/68 benign lesions and 9/53 MPNST. Two of 68 benign lesions and 7/53 (13%) MPNST had at least 5% PD-L1 staining. CD8 staining of at least 5% was seen in 1/20 (5%) nerves, 45/68 (66%) benign lesions and 30/53 (57%) MPNST. PD-L1 was statistically more prevalent in MPNST than both nerves and benign lesions (p=0.049 and p=0.008, respectively). Expression of PD-1 was absent in all tissue specimens. There was no correlation of PD-L1 or CD8 expression with disease state (primary versus metastatic) or patient survival.MethodsA comprehensive PNST tissue microarray was created from 141 surgical specimens including primary, recurrent, and metastatic MPNST (n=53), neurofibromas (n=57), schwannoma (n=11), and normal nerve (n=20). Cores were stained in triplicate for PD-L1, PD-1, and CD8, and expression compared between tumor types. These data were then examined for survival correlates in 35 patients with primary MPNST.ConclusionsMPNST is characterized by low PD-L1 and absent PD-1 expression with significant CD8+ TIL presence. MPNST immune microenvironment does not correlate with patient outcome.
Published: 2016

10. Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer.

Author: Andradas, Clara, Blasco-Benito, Sandra, Castillo-Lluva, Sonia, Dillenburg-Pilla, Patricia, Diez-Alarcia, Rebeca, Juanes-García, Alba, García-Taboada, Elena, Hernando-Llorente, Rodrigo, Soriano, Joaquim, Hamann, Sigrid, Wenners, Antonia, Alkatout, Ibrahim, Klapper, Wolfram, Rocken, Christoph, Bauer, Maret, Arnold, Norbert, Quintanilla, Miguel, Megías, Diego, Vicente-Manzanares, Miguel, Urigüen, Leyre, Gutkind, J, Guzmán, Manuel, Pérez-Gómez, Eduardo, and Sánchez, Cristina
Subjects: G protein-coupled receptor, GPR55, cannabinoids, metastasis, triple-negative breast cancer, Adenovirus E1A Proteins, Cell Line, Tumor, Extracellular Signal-Regulated MAP Kinases, Female, GTP-Binding Protein alpha Subunits, Gq-G11, Humans, Lysophospholipids, Neoplasm Metastasis, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-ets, Receptors, Cannabinoid, Receptors, G-Protein-Coupled, Triple Negative Breast Neoplasms, rhoA GTP-Binding Protein
Abstract: The orphan G protein-coupled receptor GPR55 has been directly or indirectly related to basic alterations that drive malignant growth: uncontrolled cancer cell proliferation, sustained angiogenesis, and cancer cell adhesion and migration. However, little is known about the involvement of this receptor in metastasis. Here, we show that elevated GPR55 expression in human tumors is associated with the aggressive basal/triple-negative breast cancer population, higher probability to develop metastases, and therefore poor patient prognosis. Activation of GPR55 by its proposed endogenous ligand lysophosphatidylinositol confers pro-invasive features on breast cancer cells both in vitro and in vivo. Specifically, this effect is elicited by coupling to Gq/11 heterotrimeric proteins and the subsequent activation, through ERK, of the transcription factor ETV4/PEA3. Together, these data show that GPR55 promotes breast cancer metastasis, and supports the notion that this orphan receptor may constitute a new therapeutic target and potential biomarker in the highly aggressive triple-negative subtype.
Published: 2016

11. Inhibition of miR-10b treats metastatic breast cancer by targeting stem cell-like properties.

Author: Halim A, Al-Qadi N, Kenyon E, Conner KN, Mondal SK, Medarova Z, and Moore A
Subjects: Humans, Female, Animals, Mice, Cell Line, Tumor, Breast Neoplasms genetics, Breast Neoplasms pathology, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Neoplasm Metastasis, Gene Expression Regulation, Neoplastic, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms pathology, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms metabolism, Cell Proliferation drug effects, Cell Movement drug effects, Xenograft Model Antitumor Assays, MicroRNAs genetics, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells drug effects, Neoplastic Stem Cells pathology
Abstract: Despite advances in breast cancer screening and treatment, prognosis for metastatic disease remains dismal at 30% five-year survival. This is due, in large, to the failure of current therapeutics to target properties unique to metastatic cells. One of the drivers of metastasis is miR-10b, a small noncoding RNA implicated in cancer cell invasion, migration, viability, and proliferation. We have developed a nanodrug, termed MN-anti-miR10b, that delivers anti-miR-10b antisense oligomers to cancer cells. In mouse models of metastatic triple-negative breast cancer, MN-anti-miR10b has been shown to prevent onset of metastasis and eliminate existing metastases in combination with chemotherapy, even after treatment has been stopped. Recent studies have implicated miR-10b in conferring stem cell-like properties onto cancer cells, such as chemoresistance. In this study, we show transcriptional evidence that inhibition of miR-10b with MN-anti-miR10b activates developmental processes in cancer cells and that stem-like cancer cells have increased miR-10b expression. We then demonstrate that treatment of breast cancer cells with MN-anti-miR10b reduces their stemness, confirming that these properties make metastatic cells susceptible to the nanodrug actions. Collectively, these findings indicate that inhibition of miR-10b functions to impair breast cancer cell stemness, positioning MN-anti-miR10b as an effective treatment option for stem-like breast cancer subtypes.
Published: 2024
Full Text: View/download PDF

12. Retraction: CUL4B promotes bladder cancer metastasis and induces epithelial-to-mesenchymal transition by activating the Wnt/β-catenin signaling pathway.

Author: Mao XW, Xiao JQ, Xu G, Li ZY, Wu HF, Li Y, Zheng YC, and Zhang N
Subjects: Humans, Neoplasm Metastasis, beta Catenin metabolism, Animals, Epithelial-Mesenchymal Transition, Urinary Bladder Neoplasms pathology, Urinary Bladder Neoplasms metabolism, Urinary Bladder Neoplasms genetics, Wnt Signaling Pathway, Cullin Proteins metabolism, Cullin Proteins genetics
Published: 2024
Full Text: View/download PDF

13. How to deal with runaway metastatic disease?

Author: Paris J and Bousquet G
Subjects: Humans, Neoplasms pathology, Neoplasms therapy, Neoplasm Metastasis
Published: 2024
Full Text: View/download PDF

14. Using early on-treatment circulating tumor DNA measurements as response assessment in metastatic castration resistant prostate cancer.

Author: Tolmeijer SH, Boerrigter E, Van Erp NP, and Mehra N
Subjects: Humans, Male, Neoplasm Metastasis, Treatment Outcome, Biomarkers, Tumor blood, Biomarkers, Tumor genetics, Prostatic Neoplasms, Castration-Resistant blood, Prostatic Neoplasms, Castration-Resistant drug therapy, Prostatic Neoplasms, Castration-Resistant pathology, Prostatic Neoplasms, Castration-Resistant genetics, Circulating Tumor DNA blood, Circulating Tumor DNA genetics
Published: 2024
Full Text: View/download PDF

15. When does a melanoma metastasize? Implications for management.

Author: Thompson JF and Williams GJ
Subjects: Humans, Neoplasm Metastasis, Skin Neoplasms pathology, Skin Neoplasms therapy, Melanoma secondary, Melanoma therapy
Abstract: Selecting which patients with clinically-localized melanoma require treatment other than wide excision of the primary tumor is based on the risk or presence of metastatic disease. This in turn is linked to survival. Knowing if and when a melanoma is likely to metastasize is therefore of great importance. Several studies employing a range of different methodologies have suggested that many melanomas metastasize long before the primary lesion is diagnosed. Therefore, waiting for dissemination of metastatic disease to become evident before making systemic therapy available to these patients may be less effective than giving them post-operative adjuvant therapy initially if the metastatic risk is high. The identification of these high-risk patients will assist in selecting those to whom adjuvant systemic therapy can most appropriately be offered. Further studies are required to better identify high-risk patients whose primary melanoma is likely to have already metastasized.
Published: 2024
Full Text: View/download PDF

16. MicroRNA-155 expression is independently predictive of outcome in chordoma

Author: Osaka, Eiji, Kelly, Andrew D, Spentzos, Dimitrios, Choy, Edwin, Yang, Xiaoqian, Shen, Jacson K, Yang, Pei, Mankin, Henry J, Hornicek, Francis J, and Duan, Zhenfeng
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biotechnology, Genetics, Aged, Aged, 80 and over, Cell Division, Cell Line, Tumor, Cell Movement, Chordoma, Female, Humans, Kaplan-Meier Estimate, Lumbar Vertebrae, Male, MicroRNAs, Middle Aged, Muscle, Skeletal, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasm Staging, Prognosis, RNA, Neoplasm, Sacrum, Spinal Neoplasms, miRNA-155, chordoma, prognosis, miRNA microarray assay, RT-PCR, Oncology and carcinogenesis
Abstract: BackgroundChordoma pathogenesis remains poorly understood. In this study, we aimed to evaluate the relationships between microRNA-155 (miR-155) expression and the clinicopathological features of chordoma patients, and to evaluate the functional role of miR-155 in chordoma.MethodsThe miRNA expression profiles were analyzed using miRNA microarray assays. Regulatory activity of miR-155 was assessed using bioinformatic tools. miR-155 expression levels were validated by reverse transcription-polymerase chain reaction. The relationships between miR-155 expression and the clinicopathological features of chordoma patients were analyzed. Proliferative, migratory and invasive activities were assessed by MTT, wound healing, and Matrigel invasion assays, respectively.ResultsThe miRNA microarray assay revealed miR-155 to be highly expressed and biologically active in chordoma. miR-155 expression in chordoma tissues was significantly elevated, and this expression correlated significantly with disease stage (p = 0.036) and the presence of metastasis (p = 0.035). miR-155 expression also correlated significantly with poor outcomes for chordoma patients (hazard ratio, 5.32; p = 0.045). Inhibition of miR-155 expression suppressed proliferation, and the migratory and invasive activities of chordoma cells.ConclusionsWe have shown miR-155 expression to independently affect prognosis in chordoma. These results collectively indicate that miR-155 expression may serve not only as a prognostic marker, but also as a potential therapeutic target in chordoma.
Published: 2015

17. Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer

Author: Gao, Yan, Foster, Rosemary, Yang, Xiaoqian, Feng, Yong, Shen, Jacson K, Mankin, Henry J, Hornicek, Francis J, Amiji, Mansoor M, and Duan, Zhenfeng
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Ovarian Cancer, Cancer, Biotechnology, Rare Diseases, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Animals, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Ovarian Epithelial, Cell Line, Tumor, Drug Resistance, Neoplasm, Female, Gene Expression Regulation, Neoplastic, Humans, Hyaluronan Receptors, Mice, Mice, Inbred BALB C, Mice, Nude, Mice, Transgenic, Neoplasm Metastasis, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Paclitaxel, Recurrence, Up-Regulation, Xenograft Model Antitumor Assays, ovarian cancer, CD44, tissue microarray, Pgp, paclitaxel, Oncology and carcinogenesis
Abstract: The clinical significance of Cluster of Differentiation 44 (CD44) remains controversial in human ovarian cancer. The aim of this study is to evaluate the clinical significance of CD44 expression by using a unique tissue microarray, and then to determine the biological functions of CD44 in ovarian cancer. In this study, a unique ovarian cancer tissue microarray (TMA) was constructed with paired primary, metastatic, and recurrent tumor tissues from 26 individual patients. CD44 expression in TMA was assessed by immunohistochemistry. Both the metastatic and recurrent ovarian cancer tissues expressed higher level of CD44 than the patient-matched primary tumor. A significant association has been shown between CD44 expression and both the disease free survival and overall survival. A strong increase of CD44 was found in the tumor recurrence of mouse model. Finally, when CD44 was knocked down, proliferation, migration/invasion activity, and spheroid formation were significantly suppressed, while drug sensitivity was enhanced. Thus, up-regulation of CD44 represents a crucial event in the development of metastasis, recurrence, and drug resistance to current treatments in ovarian cancer. Developing strategies to target CD44 may prevent metastasis, recurrence, and drug resistance in ovarian cancer.
Published: 2015

18. Cyclin alterations in diverse cancers: Outcome and co-amplification network

Author: Schwaederlé, Maria, Daniels, Gregory A, Piccioni, David E, Fanta, Paul T, Schwab, Richard B, Shimabukuro, Kelly A, Parker, Barbara A, and Kurzrock, Razelle
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Digestive Diseases, Biomarkers, Tumor, Cyclins, Disease-Free Survival, Female, Gene Amplification, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Genetic Predisposition to Disease, Humans, Kaplan-Meier Estimate, Logistic Models, Male, Middle Aged, Multivariate Analysis, Neoplasm Metastasis, Neoplasm Recurrence, Local, Neoplasms, Odds Ratio, Phenotype, Proportional Hazards Models, Retrospective Studies, Risk Factors, Time Factors, cyclin, next generation sequencing, molecular profile, amplification, Oncology and carcinogenesis
Abstract: Cyclin genes are key regulatory components of the cell cycle. With the development of new agents, cyclin-related genes are becoming increasingly important as they can be targeted. Yet, the biological implications of these alterations have not been fully studied. Clinical characteristics and outcome parameters were compared for patients harboring cyclin alterations versus not. CCN alterations were found in 13% of our population (50/392; all amplifications) and were associated with breast cancer (P < 0.0001), a higher median number of concomitant molecular alterations (P < 0.0001), and liver metastases (P = 0.046). Harboring a cyclin amplification was not associated with overall survival, the time to metastasis/recurrence, nor with the best progression-free survival. In a Cox regression model, gastrointestinal histology (P < 0.0001), PTEN (P < 0.0001), and CDK alterations (P = 0.041) had a significant association with poorer overall survival. CCN amplifications significantly correlated with alterations in FGF/FGFR family genes as well as in MET and ARFRP1. An extended correlation study shed light on a network of co-amplifications influenced in part by genes that were localized on the same amplicons. CCN amplifications are common across cancers and had distinctive biological associations. Customized combinations targeting the cyclin pathway as well as the extended co- amplification network may be necessary in order to address resistance mechanisms.
Published: 2015

19. Inhibition of spontaneous and experimental lung metastasis of soft-tissue sarcoma by tumor-targeting Salmonella typhimurium A1-R

Author: Miwa, Shinji, Zhang, Yong, Baek, Kyung-Eun, Uehara, Fuminari, Yano, Shuya, Yamamoto, Mako, Hiroshima, Yukihiko, Matsumoto, Yasunori, Kimura, Hiroaki, Hayashi, Katsuhiro, Yamamoto, Norio, Bouvet, Michael, Tsuchiya, Hiroyuki, Hoffman, Robert M, and Zhao, Ming
Subjects: Cancer, Lung, Lung Cancer, Emerging Infectious Diseases, Orphan Drug, Rare Diseases, Animals, Cell Line, Tumor, Disease Models, Animal, Female, Fibrosarcoma, Humans, Lung Neoplasms, Mice, Mice, Nude, Neoplasm Metastasis, Prognosis, Salmonella typhimurium, Sarcoma, Xenograft Model Antitumor Assays, HT-1080, orthotopic model, nude mice, lung metastasis, bacterial therapy, Oncology and Carcinogenesis
Abstract: Prognosis of patients with lung metastases of soft-tissue sarcoma is still poor. Therefore, novel systemic therapy is needed to improve the survival of soft-tissue sarcoma. In the present study, tumor-targeting therapy with a genetically-modified auxotrophic strain of Salmonella typhimurium, termed A1-R, was evaluated. Mouse models of primary soft tissue sarcoma and spontaneous lung metastasis were obtained by orthotopic intra-muscular injection of HT1080-RFP human fibrosarcoma cells. S. typhimurium A1-R was administered from day 14, once a week for two weeks. On day 28, lung samples were excised and observed with a fluorescence imaging system. The number of lung metastasis was 8.8 ± 3.4 in the untreated group and 0.8 ± 0.8 in the treated group (P = 0.024). A mouse model of experimental lung metastasis was obtained by tail vein injection of HT1080-RFP cells. The mice were treated with S. typhimurium A1-R (i.v.) on day 7, once a week for three weeks. S. typhimurium A1-R significantly reduced lung metastases and improved overall survival (P = 0.004). S. typhimurium A1-R bacterial therapy has future potential for treating advanced soft tissue sarcoma and improving prognosis of patients with lung metastasis.
Published: 2014

20. Targeted PI3K/AKT/mTOR therapy for metastatic carcinomas of the cervix: A phase I clinical experience

Author: Hou, Ming-Mo, Liu, Xiaochun, Wheler, Jennifer, Naing, Aung, Hong, David, Coleman, Robert L, Tsimberidou, Apostolia, Janku, Filip, Zinner, Ralph, Lu, Karen, Kurzrock, Razelle, and Fu, Siqing
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Prevention, Vaccine Related, Cancer, Clinical Research, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Squamous Cell, Class I Phosphatidylinositol 3-Kinases, Female, Humans, Middle Aged, Molecular Targeted Therapy, Neoplasm Metastasis, PTEN Phosphohydrolase, Phosphatidylinositol 3-Kinases, Phosphoinositide-3 Kinase Inhibitors, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases, Uterine Cervical Neoplasms, Cervical Cancer, Phase I Trial, Matched Therapy, PIK3CA mutation, PTEN loss, Oncology and carcinogenesis
Abstract: BackgroundActivated PI3K/AKT/mTOR pathway frequently occurs in metastatic or recurrent cervical carcinomas. However, the clinical benefits of matched therapy, a therapeutic approach targeting a specific mutational abnormality, have not yet been established.MethodsWe analyzed the outcomes of patients with metastatic or recurrent cervical carcinomas who had a test for PIK3CA mutation and/or PTEN loss/mutation, and received ≥1 phase I therapeutic regimen between January 2006 and June 2013.ResultsPatients with adenocarcinoma had fewer PIK3CA mutations (14%), and survived longer (median, 14.2 months) than those with squamous cell carcinoma (48% and 7.2 months; p = 0.016, and 0.001, respectively). Matched therapy targeting the activated PI3K/AKT/mTOR pathway led to a favorable rate of SD ≥ 6 months/CR/PR (53%) and significantly longer progression-free survival (median, 6.0 months) than non-matched therapy (11% and 1.5 months; p = 0.08 and 0.026; respectively). In patients with squamous cell carcinoma of the cervix, the presence of PIK3CA mutations was associated with a significantly longer overall survival (median, 9.4 months) than the absence of PIK3CA mutations (median, 4.2 months; p = 0.019).ConclusionsMatched therapy targeting the activated PI3K/AKT/mTOR pathway provided meaningful clinical benefits. Thus, further evaluation of PI3K/AKT/mTOR pathway targeted therapy is warranted, especially in metastatic or recurrent squamous cell carcinoma.
Published: 2014

21. An interferon signature identified by RNA-sequencing of mammary tissues varies across the estrous cycle and is predictive of metastasis-free survival

Author: Snijders, Antoine M, Langley, Sasha, Mao, Jian-Hua, Bhatnagar, Sandhya, Bjornstad, Kathleen A, Rosen, Chris J, Lo, Alvin, Huang, Yurong, Blakely, Eleanor A, Karpen, Gary H, Bissell, Mina J, and Wyrobek, Andrew J
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Estrogen, Breast Cancer, Prevention, Genetics, Women's Health, Cancer, 2.1 Biological and endogenous factors, Aetiology, Animals, Disease-Free Survival, Estrous Cycle, Female, Humans, Interferons, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Neoplasm Metastasis, RNA, Messenger, estrous cycle, mammary gland, RNA-sequencing, Type-1 interferon, low-dose ionizing radiation, immunity, breast cancer, genetic susceptibility, Oncology and carcinogenesis
Abstract: The concept that a breast cancer patient's menstrual stage at the time of tumor surgery influences risk of metastases remains controversial. The scarcity of comprehensive molecular studies of menstrual stage-dependent fluctuations in the breast provides little insight in this observation. To gain a deeper understanding of the biological changes in mammary tissue and blood during the menstrual cycle and to determine the influence of environmental exposures, such as low-dose ionizing radiation (LDIR), we used the mouse to characterize estrous-cycle variations in mammary gene transcripts by RNA-sequencing, peripheral white blood cell (WBC) counts and plasma cytokine levels. We identified an estrous-variable and hormone-dependent gene cluster enriched for Type-1 interferon genes. Cox regression identified a 117-gene signature of interferon-associated genes, which correlated with lower frequencies of metastasis in breast cancer patients. LDIR (10cGy) exposure had no detectable effect on mammary transcripts. However, peripheral WBC counts varied across the estrous cycle and LDIR exposure reduced lymphocyte counts and cytokine levels in tumor-susceptible mice. Our finding of variations in mammary Type-1 interferon and immune functions across the estrous cycle provides a mechanism by which timing of breast tumor surgery during the menstrual cycle may have clinical relevance to a patient's risk for distant metastases.
Published: 2014

22. Oncogenic function and prognostic significance of protein tyrosine phosphatase PRL-1 in hepatocellular carcinoma

Author: Jin, Shaowen, Wang, Kaimei, Xu, Kang, Xu, Junyao, Sun, Jian, Chu, Zhonghua, Lin, Dechen, Koeffler, Phillip H, Wang, Jie, and Yin, Dong
Subjects: Rare Diseases, Liver Disease, Liver Cancer, Cancer, Digestive Diseases, 2.1 Biological and endogenous factors, Aetiology, Cadherins, Carcinoma, Hepatocellular, Cell Cycle Proteins, Cell Movement, Female, Gene Amplification, Gene Dosage, HEK293 Cells, Hep G2 Cells, Humans, Liver Neoplasms, Male, Membrane Proteins, Middle Aged, Neoplasm Metastasis, Phosphatidylinositol 3-Kinases, Prognosis, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins c-akt, Signal Transduction, Hepatocellular carcinoma, PRL-1, SNP-Chip, Tumor metastasis, Prognostic marker, Oncology and Carcinogenesis
Abstract: Our SNP-Chip data demonstrated 7/60 (12%) hepatocellular carcinoma (HCC) patients had PRL-1 copy number amplification. However, its biological functions and signaling pathways in HCC are deficient. Here, we investigated its oncogenic function and prognostic significance in HCC. PRL-1 protein levels were examined in 167 HCC samples by immunohistochemisty (IHC). The relationship of PRL-1 expression and clinicopathological features was assessed by correlation, Kaplan-Meier and Cox regression analyses. The oncogenic function of PRL-1 in HCC cells and its underlying mechanism were investigated by ectopic overexpression and knockdown model. PRL-1 levels in primary HCC and metastatic intravascular cancer thrombus were also determined by IHC. PRL-1 levels were frequently elevated in HCC tissues (81%), and elevated expression of PRL-1 was significantly associated with more aggressive phenotype and poorer prognosis in HCC patients (p
Published: 2014

23. To grab the stroma by the horns: from biology to cancer therapy with mesenchymal stem cells.

Author: Droujinine, Ilia A, Eckert, Mark A, and Zhao, Weian
Subjects: Cell Differentiation, Cell Movement, Cell Proliferation, Cell Transformation, Neoplastic, Humans, Mesenchymal Stem Cell Transplantation, Mesenchymal Stromal Cells: metabolism, Neoplasm Metastasis, Neoplasms: therapy, Tumor Microenvironment, UCI Libraries Open Access Publishing Fund
Abstract: Mesenchymal stem or stromal cells (MSCs) are precursor cells that play important roles in tumorigenesis. MSCs are recruited to tumors from local and distant sources to form part of the tumor microenvironment. MSCs influence tumor progression by interacting with cancer cells, endothelial cells, immune cells, and cancer stem cells, in a context-dependent network. This review aims to synthesize this emerging yet controversial field to identify key questions regarding the mechanisms of MSC mobilization and survival in blood; homing to tumors, metastases, and premetastatic sites; spatiotemporal organization and differentiation; and interaction with immune cells and cancer stem cells. Understanding the fundamental biology underlying mesenchymal stem cell and tumor interactions has the potential to inform our knowledge of cancer initiation and progression as well as lead to novel therapeutics for cancer. Furthermore, knowledge of endogenous mechanisms can be used to "program" exogenous MSCs for targeted chemotherapeutic delivery to tumors and metastases. Emerging studies will provide crucial insight into the mechanisms of tumor interactions with the whole organism including MSCs.
Published: 2013

24. Targeted Therapy of Advanced Gallbladder Cancer and Cholangiocarcinoma with Aggressive Biology: Eliciting Early Response Signals from Phase 1 trials

Author: Subbiah, Ishwaria M, Subbiah, Vivek, Tsimberidou, Apostolia M, Naing, Aung, Kaseb, Ahmed O, Javle, Milind, Fu, Siqing, Hong, David S, Piha-Paul, Sarina, Wheler, Jennifer J, Hess, Kenneth R, Janku, Filip, Falchook, Gerald S, Wolff, Robert A, and Kurzrock, Razelle
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Digestive Diseases, Clinical Trials and Supportive Activities, Liver Disease, Cancer, Development of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Adult, Aged, Analysis of Variance, Antineoplastic Combined Chemotherapy Protocols, Arteriovenous Fistula, Bile Duct Neoplasms, Bile Ducts, Intrahepatic, Cholangiocarcinoma, Disease-Free Survival, Female, Gallbladder Neoplasms, Gastrointestinal Hemorrhage, Humans, Male, Middle Aged, Neoplasm Metastasis, Organoplatinum Compounds, Oxaliplatin, Treatment Outcome, gallbladder carcinoma, cholangiocarcinoma, phase I, targeted therapy, locoregional therapy, Oncology and carcinogenesis
Abstract: PurposePatients with advanced cholangiocarcinoma (CC) and gallbladder carcinoma (GC) have few therapeutic options for relapsed disease. methods: Given the overall poor prognosis in this population and the availability of novel targeted therapies, we systematically analyzed the characteristics and outcomes for GC and CC patients treated on phase I trials with an emphasis on targeted agents and locoregional therapies.ResultsOf 40 treated patients (GC=6; CC=34; median age, 60 years), 8 (20%) had stable disease (SD) > 6 months, 3 (8%) partial response (PR), on protocols with hepatic arterial drug infusion and anti-angiogenic, anti-HER-2/neu or novel MAPK/ERK kinase (MEK) inhibitors. Median progression-free survival (PFS) on phase I trials was 2.0 months (95% CI 1.7, 2.8) versus 3.0 months (95% CI 2.4, 5.0), 3.0 months (95% CI 2.3, 4.6), and 3.0 months (95% CI 2.4, 3.9) for their first-, second-, and last-line FDA-approved therapy. In univariate analysis, >3 metastatic sites, elevated alanine aminotransferase (ALT) (>56IU/L), serum creatinine (>1.6mg/dL), and CA19-9 (>35U/mL) were associated with a shorter PFS. Mutational analysis revealed mutation in the KRAS oncogene in 2 of 11 patients (18%). The SD >6 months/PR rate of 28% was seen with hepatic arterial infusion of oxaliplatin, and inhibitors of angiogenesis, HER-2/neu or MEK.ConclusionsThe PFS in phase I trials was similar to that of the first, second, and last-line therapy (P=0.95, 0.98, 0.76, respectively) with FDA-approved agents given in the advanced setting, emphasizing a role for targeted agents in a clinical trials setting as potentially valuable therapeutic options for these patients.
Published: 2013

25. Role of germline variants in the metastasis of breast carcinomas

Author: Ángela Santonja, Aurelio A. Moya-García, Nuria Ribelles, Begoña Jiménez-Rodríguez, Bella Pajares, Cristina E. Fernández-De Sousa, Elísabeth Pérez-Ruiz, María del Monte-Millán, Manuel Ruiz-Borrego, Juan de la Haba, Pedro Sánchez-Rovira, Atocha Romero, Anna González-Neira, Ana Lluch, and Emilio Alba
Subjects: Oncology, Tumor Microenvironment, Humans, Breast Neoplasms, Neoplasm Metastasis, Germ-Line Mutation, Genome-Wide Association Study
Abstract: Most cancer-related deaths in breast cancer patients are associated with metastasis, a multistep, intricate process that requires the cooperation of tumour cells, tumour microenvironment and metastasis target tissues. It is accepted that metastasis does not depend on the tumour characteristics but the host's genetic makeup. However, there has been limited success in determining the germline genetic variants that influence metastasis development, mainly because of the limitations of traditional genome-wide association studies to detect the relevant genetic polymorphisms underlying complex phenotypes. In this work, we leveraged the extreme discordant phenotypes approach and the epistasis networks to analyse the genotypes of 97 breast cancer patients. We found that the host's genetic makeup facilitates metastases by the dysregulation of gene expression that can promote the dispersion of metastatic seeds and help establish the metastatic niche-providing a congenial soil for the metastatic seeds.
Published: 2022

26. Tumor necroptosis promotes metastasis through modulating the interplay between tumor and host immunity.

Author: Liu Z, Choksi S, and Liu ZG
Subjects: Humans, Cell Movement, Cadherins, Neoplasm Metastasis, Necroptosis, Neoplasms pathology
Published: 2023
Full Text: View/download PDF

27. Correction: Musashi2 promotes the development and progression of pancreatic cancer by down-regulating Numb protein

Author: Sheng, Weiwei, Dong, Ming, Chen, Chuanping, Li, Yang, Liu, Qingfeng, and Dong, Qi
Subjects: Male, Blotting, Western, Down-Regulation, Mice, Nude, Apoptosis, Nerve Tissue Proteins, Immunoenzyme Techniques, Mice, Biomarkers, Tumor, Tumor Cells, Cultured, Animals, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Aged, Neoplasm Staging, Liver Neoplasms, Correction, Membrane Proteins, RNA-Binding Proteins, Prognosis, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, Survival Rate, Oncology, Case-Control Studies, Disease Progression, Female, Follow-Up Studies
Abstract: Musashi2-Numb interaction plays a vital role in the progression of myeloid leukemia. However, its potential role in solid cancers has rarely been reported. We investigated the coordinate function of Musashi2-Numb in the development of pancreatic cancer (PC) in vitro and vivo. Both Musashi2 protein and mRNA levels were higher in PC tissues than that in paired normal pancreas (P0.05). Musashi2 overexpression and Numb positive expression were positively and negatively associated with tumor size and UICC stage, respectively (P0.05). Multivariate analysis identified Musashi2 and Numb as adverse and favorable independent indicators for the survival of PC patients. Moreover, patients with high Musashi2 expression combining with negative Numb expression had a significantly worse overall survival (P=0.001). The negative relationship between Musashi2 and Numb was found at both PC tissue and cell levels. These two endogenous proteins can be co-immunoprecipitated from PC cell lines, and Musashi2 silence up-regulated Numb protein in vitro and vivo. Meanwhile, its silence decreased cell invasion and migration in vitro and inhibited the growth of subcutaneous tumors and the frequency of liver metastasis in vivo. However, Numb knockdown significantly reversed the decrease of cell invasion and migration induced by Musashi2 silence. Musashi2 promotes the development and progression of pancreatic cancer by down-regulating Numb protein. The interaction of Musashi2-Numb plays a significant role in the development and progression of PC.
Published: 2022

28. Molecular imaging with positron emission tomography and computed tomography (PET/CT) for selecting first-line targeted treatment in metastatic breast cancer: a cost-effectiveness study

Author: Erik F. J. de Vries, David Parkin, Marcel J. W. Greuter, Rositsa G Koleva-Kolarova, Talitha L Feenstra, Erik Buskens, Geertruida H. de Bock, Karin M. Vermeulen, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Value, Affordability and Sustainability (VALUE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Life Course Epidemiology (LCE), and Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)
Subjects: 89Zr-trastuzumab, medicine.medical_specialty, positron emission tomography, Cost effectiveness, diagnostic imaging, First line, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, neoplasm metastasis, 0302 clinical medicine, breast neoplasm, medicine, Medical imaging, skin and connective tissue diseases, health care economics and organizations, PET-CT, medicine.diagnostic_test, business.industry, medicine.disease, Metastatic breast cancer, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, Radiology, Molecular imaging, business, Progressive disease, Research Paper
Abstract: Our aim was to evaluate the potential cost-effectiveness of PET/CT with FES and 89Zr-trastuzumab compared to pathology to select first-line targeted treatment in metastatic breast cancer (MBC) patients with non-rapidly progressive disease. A previously published and validated model was extended and adapted for this analysis. Two alternative scenarios were compared. In the care as usual pathway first-line targeted treatment of MBC patients was assigned on the basis of pathology results, while in the intervention pathway treatment selection was based on the results from the PET/CT imaging. Costs, life years gained (LYG) and incremental cost-effectiveness ratios (ICER) were calculated. More MBC lesions were detected in the intervention pathway than in the care as usual pathway. The diagnostic costs to evaluate the receptor status and the treatment costs were higher in the intervention strategy, as were total costs and total LYG. The ICER for replacing biopsies with PET/CT imaging with FES and 89Zr-trastuzumab, assuming sensitivity of 77.1% and specificity of 80%, ranged from €71,000 to €77,000 per LYG. When assuming sensitivity of 80% and specificity of 76.7%, the ICER for replacing biopsies with PET/CT imaging with FES and 89Zr-trastuzumab ranged from to €74,000 to €80,000 per LYG. The application of PET/CT with FES and 89Zr-trastuzumab in first-line treatment selection for MBC patients has the potential to be a cost-effective intervention. Our analysis demonstrated that even a small increase in the sensitivity and the specificity of PET/CT can have a large impact on its potential cost-effectiveness.
Published: 2018

29. Role of germline variants in the metastasis of breast carcinomas.

Author: Santonja Á, Moya-García AA, Ribelles N, Jiménez-Rodríguez B, Pajares B, Fernández-De Sousa CE, Pérez-Ruiz E, Del Monte-Millán M, Ruiz-Borrego M, de la Haba J, Sánchez-Rovira P, Romero A, González-Neira A, Lluch A, and Alba E
Subjects: Breast Neoplasms genetics, Genome-Wide Association Study, Humans, Tumor Microenvironment, Germ-Line Mutation, Neoplasm Metastasis
Abstract: Most cancer-related deaths in breast cancer patients are associated with metastasis, a multistep, intricate process that requires the cooperation of tumour cells, tumour microenvironment and metastasis target tissues. It is accepted that metastasis does not depend on the tumour characteristics but the host's genetic makeup. However, there has been limited success in determining the germline genetic variants that influence metastasis development, mainly because of the limitations of traditional genome-wide association studies to detect the relevant genetic polymorphisms underlying complex phenotypes. In this work, we leveraged the extreme discordant phenotypes approach and the epistasis networks to analyse the genotypes of 97 breast cancer patients. We found that the host's genetic makeup facilitates metastases by the dysregulation of gene expression that can promote the dispersion of metastatic seeds and help establish the metastatic niche-providing a congenial soil for the metastatic seeds., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results., (Copyright: © 2022 Santonja et al.)
Published: 2022
Full Text: View/download PDF

30. The effect of CA125 on metastasis of ovarian cancer: old marker new function

Author: Yunde Liu, Xiaoxu Yu, Jie Yang, Qianyu Huo, Huijing Bao, Chen Xu, Weiwei Yang, Jiayin Song, Hongyan Wang, and Qin Yuan
Subjects: Adult, 0301 basic medicine, medicine.medical_specialty, endocrine system diseases, Wnt pathway, cut-off value, Metastasis, CA125, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Biomarkers, Tumor, metastasis, Humans, Medicine, Neoplasm Metastasis, Wnt Signaling Pathway, Inhibitory effect, Aged, Cell Proliferation, Ovarian Neoplasms, Gynecology, business.industry, Disease progression, Wnt signaling pathway, Area under the curve, Cancer, Middle Aged, Prognosis, medicine.disease, female genital diseases and pregnancy complications, ovarian cancer, 030104 developmental biology, Clinical research, ROC Curve, Oncology, CA-125 Antigen, 030220 oncology & carcinogenesis, Female, business, Ovarian cancer, Research Paper
Abstract: // Qin Yuan 1, * , Jiayin Song 2, * , Weiwei Yang 3 , Hongyan Wang 1 , Qianyu Huo 1 , Jie Yang 1 , Xiaoxu Yu 3 , Yunde Liu 1 , Chen Xu 4 and Huijing Bao 1 1 School of Laboratory Science, Tianjin Medical University, Tianjin, China 2 The Department of Clinical Laboratory, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China 3 The Department of Laboratory Science, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China 4 The Department of Laboratory Science, Tianjin Fourth Central Hospital, Tianjin, China * These authors have contributed equally to this work Correspondence to: Huijing Bao, email: kris_10713@126.com Chen Xu, email: skyalong1028@163.com Yunde Liu, email: yundeliu@163.com Keywords: ovarian cancer, metastasis, CA125, Wnt pathway, cut-off value Received: September 30, 2016 Accepted: May 04, 2017 Published: June 07, 2017 ABSTRACT CA125 has been used extensively to screen for neoplasms, especially in ovarian cancer. The serum CA125 level can be used as a better prognosis evaluation and it may dynamic monitoring the disease progression. We explored the effect of CA125 on ovarian cancer cell migration and its underlying mechanism. Transwell assays showed that exposure to 0.2 μg/ml or 0.4 μg/ml CA125 for 48 h increased migration of A2780 and OVCAR-3 ovarian cancer cells. This effect of CA125 was blocked addition of 200 ng/ml DKK-1, a Wnt pathway inhibitor. Conversely, addition of CA125 reversed the inhibitory effect of Wnt inhibition in A2780 cells pretreated with DKK-1. Examination of CA125 levels in serum from 97 ovarian cancer patients revealed no relationship between a patient’s age or CA125 level currently used clinically for ovarian cancer diagnosis and metastasis. However, using receiver operating characteristic (ROC) curves, we identified a new cut-off value for the serum CA125 concentration (82.9 U/ml) that is predictive of metastasis. The area under the curve is 0.632. This new cut-off value has the potential to serve as a clinically useful indicator of metastasis in ovarian cancer patients.
Published: 2017

31. Tumor diversity and evolution revealed through RADseq

Author: Jun Cai, Elizabeth B. Perry, Charles K. Kaufman, Richard M. White, Alvin Makohon-Moore, Christine A. Iacobuzio-Donahue, and Caihong Zheng
Subjects: 0301 basic medicine, tumor evolution, Genomics, Biology, Genome, DNA sequencing, Animals, Genetically Modified, 03 medical and health sciences, Priority Research Perspective, Neoplasms, restriction-site associated DNA sequencing, Exome Sequencing, medicine, cancer, Animals, Humans, Genetic Predisposition to Disease, Neoplasm Metastasis, Exome, Genetic Association Studies, Zebrafish, Neoplasm Staging, Genetics, Phylogenetic tree, Whole Genome Sequencing, Human evolutionary genetics, Mosaicism, Cancer, High-Throughput Nucleotide Sequencing, RADseq, medicine.disease, Precision medicine, 3. Good health, Disease Models, Animal, 030104 developmental biology, Oncology, Disease Progression, next-generation sequencing, Neoplasm Grading
Abstract: // Elizabeth B. Perry 1,2 , Alvin Makohon-Moore 3 , Caihong Zheng 4 , Charles K. Kaufman 5 , Jun Cai 4 , Christine A. Iacobuzio-Donahue 3 and Richard M. White 1 1 Cancer Biology & Genetics, Memorial Sloan Kettering Cancer Center, New York, New York, USA 2 Biostatistics, Yale University, New Haven, Connecticut, USA 3 The David M. Rubenstein Center for Pancreatic Cancer Research, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA 4 Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, China 5 Washington University School of Medicine, St. Louis, Missouri, USA Correspondence to: Elizabeth B. Perry, email: // Richard M. White, email: // Keywords : restriction-site associated DNA sequencing, RADseq, cancer, next-generation sequencing, tumor evolution Received : April 09, 2017 Accepted : May 12, 2017 Published : June 03, 2017 Abstract Summary: Cancer is an evolutionary disease, and there is increasing interest in applying tools from evolutionary biology to understand cancer progression. Restriction-site associated DNA sequencing (RADseq) was developed for the field of evolutionary genetics to study adaptation and identify evolutionary relationships among populations. Here we apply RADseq to study tumor evolution, which allows for unbiased sampling of any desired frequency of the genome, overcoming the selection bias and cost limitations inherent to exome or whole-genome sequencing. We apply RADseq to both human pancreatic cancer and zebrafish melanoma samples. Using either a low-frequency (SbfI, 0.4% of the genome) or high-frequency (NsiI, 6-9% of the genome) cutter, we successfully identify single nucleotide substitutions and copy number alterations in tumors, which can be augmented by performing RADseq on sublineages within the tumor. We are able to infer phylogenetic relationships between primary tumors and metastases. These same methods can be used to identify somatic mosaicism in seemingly normal, non-cancerous tissues. Evolutionary studies of cancer that focus on rates of tumor evolution and evolutionary relationships among tumor lineages will benefit from the flexibility and efficiency of restriction-site associated DNA sequencing.
Published: 2017

32. Higher platelet distribution width predicts poor prognosis in laryngeal cancer

Author: Tiemin Liu, Huan Zhang, Changsong Wang, Rui Tao Wang, Li Liu, Yan Song Liu, Kai Jiang Yu, Zhi Ping Liu, and Shuang Fu
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Kaplan-Meier Estimate, survival, Metastasis, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, medicine, platelet distribution width, Humans, Platelet activation, Neoplasm Metastasis, Mean platelet volume, Laryngeal Neoplasms, Aged, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, Platelet Count, Proportional hazards model, business.industry, Cancer, Retrospective cohort study, Middle Aged, Laryngeal Neoplasm, Prognosis, medicine.disease, Intensive care unit, Surgery, 030104 developmental biology, ROC Curve, Oncology, 030220 oncology & carcinogenesis, laryngeal cancer, Female, Neoplasm Grading, business, Mean Platelet Volume, Biomarkers, Research Paper
Abstract: // Huan Zhang 1, * , Li Liu 2, * , Shuang Fu 1, * , Yan-Song Liu 3 , Changsong Wang 3 , Tiemin Liu 1, 4 , Zhi-Ping Liu 5 , Rui-Tao Wang 1, 6 and Kai-Jiang Yu 3, 6 1 Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 150081, China 2 Department of Histology and Embryology, Harbin Medical University, Harbin, Heilongjiang, 150081, China 3 Department of Intensive Care Unit, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 150081, China 4 Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA 5 Departments of Internal Medicine and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA 6 Heilongjiang Academy of Medical Science, Harbin, Heilongjiang, 150081, China * These authors have contributed equally to this work Correspondence to: Rui-Tao Wang, email: ruitaowang@126.com Kai-Jiang Yu, email: kaijiang_yu@yeah.net Keywords: laryngeal cancer, platelet distribution width, prognosis, survival Received: March 29, 2017 Accepted: May 01, 2017 Published: May 30, 2017 ABSTRACT Background: Activated platelets promote cancer progression and metastasis. However, the prognostic value of platelet indices in laryngeal cancer remains poorly understood. The purpose of this study was to investigate the predictive significance of platelet indices in laryngeal cancer. Results: Of the 241 patients, high platelet distribution width (PDW) levels were observed in 116 (48.1 %) patients. In the Kaplan-Meier analysis, increased PDW was significantly associated with a poorer overall survival (p < 0.001). In the multivariate Cox model, PDW was an independent prognostic index for overall survival (HR=4.381, 95% CI=2.313-8.298, P < 0.001). Method: The retrospective study included 241 consecutive patients with laryngeal cancer between January 2009 and December 2009. The relationships between PDW and clinicopathological characteristics were analyzed. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of PDW. Conclusions: Elevated PDW might be a novel prognostic marker in laryngeal cancer.
Published: 2017

33. High expression of GPR116 indicates poor survival outcome and promotes tumor progression in colorectal carcinoma

Author: Sengwang Fu, Haoyan Chen, Jun Dai, Wei Liang, Xiao-Qing Tian, Li Yang, Yun-Jie Gao, Zhi-Zheng Ge, Wen-Feng Lin, and Xiao-Lu Lin
Subjects: Male, 0301 basic medicine, Oncology, Pathology, Colorectal cancer, Kaplan-Meier Estimate, Disease, medicine.disease_cause, Survival outcome, Receptors, G-Protein-Coupled, Metastasis, 0302 clinical medicine, Neoplasm Metastasis, Extracellular Signal-Regulated MAP Kinases, Middle Aged, Prognosis, Immunohistochemistry, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Disease Progression, Female, GPR116, Colorectal Neoplasms, Research Paper, medicine.medical_specialty, Epithelial-Mesenchymal Transition, 03 medical and health sciences, colorectal carcinoma, Internal medicine, medicine, Humans, metastasis, RNA, Messenger, Risk factor, neoplasms, Aged, Cell Proliferation, Neoplasm Staging, business.industry, Hepatology, medicine.disease, digestive system diseases, 030104 developmental biology, Tumor progression, Neoplasm Grading, Carcinogenesis, business, Proto-Oncogene Proteins c-akt
Abstract: // Li Yang 1, * , Xiao-Lu Lin 1, * , Wei Liang 3, * , Seng-Wang Fu 4, * , Wen-Feng Lin 1, * , Xiao-Qing Tian 1 , Yun-Jie Gao 1 , Hao-Yan Chen 2 , Jun Dai 1 and Zhi-Zheng Ge 1 1 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200001, China 2 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200001, China 3 Department of Digestive Endoscopy, Provincial Clinic Medical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, China 4 Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China * These authors have contributed equally to this work Correspondence to: Zhi-Zheng Ge, email: zhizhengge@aliyun.com Jun Dai, email: lx19980507@126.com Keywords: GPR116, prognosis, metastasis, colorectal carcinoma Received: March 22, 2017 Accepted: May 01, 2017 Published: May 25, 2017 ABSTRACT Previous studies have found that G-protein-coupled receptor 116 (GPR116) is a regulator of breast cancer metastasis. However, the role of GPR116 in colorectal carcinoma (CRC) carcinogenesis and progression is unknown. In this study, We found GPR116 expression was significantly up-regulated in CRC specimens compared with corresponding non-cancerous tissues. Increased GPR116 expression in CRC was correlated with histological differentiation and distant metastasis. In addition, high expression of GPR116 was significantly associated with poor overall survival of CRC patients, which was also confirmed by GSE14333, GSE17536 and GSE33113 datasets from the Gene Expression Omnibus (GEO). Furthermore, we demonstrated that the ability of proliferation and invasion of CRC cell lines HCT116 and LOVO was markedly reduced after transfected with siRNA-GPR116. Meanwhile, GPR116 may drive EMT in CRC cells through AKT/EKR signaling pathway, resulting in metastasis. Thus, GPR116 may be a novel reliable prognostic indicator and a risk factor in CRC progression.
Published: 2017

34. Ring finger protein 125, as a potential highly aggressive and unfavorable prognostic biomarker, promotes the invasion and metastasis of human gallbladder cancers via activating the TGF-β1-SMAD3-ID1 signaling pathway

Author: Hassan Mohamed, Jin Cao, Yue-Zu Fan, Fang-Tao Wang, Kamar Hasan Ansari, Zhong-Yan Liu, Jing-Tao Zhang, Guo-Li Xu, and Xin-Ping Li
Subjects: Inhibitor of Differentiation Protein 1, Male, 0301 basic medicine, Pathology, Vimentin, Kaplan-Meier Estimate, Metastasis, 0302 clinical medicine, Cell Movement, Neoplasm Metastasis, Aged, 80 and over, Gene knockdown, biology, Middle Aged, Prognosis, Phenotype, Tumor Burden, Oncology, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, ring finger protein 125, Female, Gallbladder Neoplasms, Signal transduction, Research Paper, Signal Transduction, signaling pathway, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Ubiquitin-Protein Ligases, Models, Biological, Transforming Growth Factor beta1, 03 medical and health sciences, Cell Line, Tumor, Biomarkers, Tumor, Cell Adhesion, medicine, metastasis, Humans, Smad3 Protein, Gallbladder cancer, Aged, Neoplasm Staging, Gene Expression Profiling, Computational Biology, medicine.disease, 030104 developmental biology, Tumor progression, biology.protein, Cancer research, Neoplasm Grading, Gallbladder Neoplasm, gallbladder neoplasm
Abstract: // Zhong-Yan Liu 1, * , Jin Cao 1, * , Jing-Tao Zhang 1, * , Guo-Li Xu 1 , Xin-Ping Li 1 , Fang-Tao Wang 1 , Kamar Hasan Ansari 1 , Hassan Mohamed 1 and Yue-Zu Fan 1 1 Department of Surgery, Tongji Hospital, Tongji University School of Medicine, Tongji University, Shanghai 200065, P.R. China * These authors have contributed equally to this work Correspondence to: Yue-Zu Fan, email: fanyuezu@hotmail.com Keywords: gallbladder neoplasm, ring finger protein 125, metastasis, prognosis, signaling pathway Received: December 10, 2016 Accepted: April 19, 2017 Published: May 25, 2017 ABSTRACT Human gallbladder cancer (GBC) is a lethal aggressive malignant neoplasm. Identification of potential molecular biomarkers and development of targeted therapeutics for GBC patients is very necessary. In this study, we firstly investigated the correlation between ring finger protein 125 (RNF125) expression and the metastasis and prognosis of GBC, and the underlying molecular mechanism. RNF125 expression in a cohort of GBC tissues was examined; its correlation with clinicopathological and prognostic factors of GBC patients was analyzed. Moreover, the metastasis-related difference expressed genes in highly and lowly aggressive GBC cell lines were identified; and the influence of RNF125 knockdown on the metastatic phenotypes and characteristic EMT markers in highly aggressive GBC NOZ cells was detected. Furthermore, the underlying molecular mechanism of RNF125 effect was explored. The results showed that RNF125 was highly expressed in GBC tissues and related with aggressive characteristics such as Nevin stage ( P = 0.041) etc. and unfavorable prognosis of GBC patients ( P = 0.023, log-rank test). And, RNF125 was proved to a positive metastasis-related gene in vitro . RNF125 knockdown inhibited the invasion and migration, enhanced the adhesion, upregulated E-cadherin and β-catenin expression, and downregulated vimentin and N-cadherin expression (all P < 0.001) of NOZ cells in vitro . RNF125 promoting effect on GBC tumor progression was identified to relate with the activation of TGF-β1-SMAD3-ID1 signaling pathway. These findings firstly confirm that high RNF125 expression is related with aggressive characteristics and unfavorable prognosis of GBC patients; RNF125 promotes the invasion and metastasis of human GBCs via activating the TGF-β1-SMAD3-ID1 signaling pathway.
Published: 2017

35. HIF-2α promotes the formation of vasculogenic mimicry in pancreatic cancer by regulating the binding of Twist1 to the VE-cadherin promoter

Author: Zi-Xiang Zhang, Ni Yin, Dechun Li, Jian Yang, Xiao-Gang Zhou, Yi Zhang, Jian Zhou, and Dongming Zhu
Subjects: Male, 0301 basic medicine, Pathology, Pancreatic disease, Angiogenesis, pancreatic cancer, Antigens, CD34, Mice, VE-cadherin, 0302 clinical medicine, Cell Movement, Basic Helix-Loop-Helix Transcription Factors, Medicine, Twist, Neoplasm Metastasis, Promoter Regions, Genetic, Aged, 80 and over, Neovascularization, Pathologic, Nuclear Proteins, HIF-2α, Middle Aged, Cadherins, Gene Expression Regulation, Neoplastic, Endothelial stem cell, Oncology, 030220 oncology & carcinogenesis, Heterografts, Female, Research Paper, Protein Binding, medicine.medical_specialty, 03 medical and health sciences, Downregulation and upregulation, Antigens, CD, Cell Line, Tumor, Pancreatic cancer, Animals, Humans, Gene silencing, Vasculogenic mimicry, Aged, vasculogenic mimicry (VM), business.industry, Twist-Related Protein 1, medicine.disease, Pancreatic Neoplasms, Disease Models, Animal, 030104 developmental biology, Cancer research, Neoplasm Grading, business
Abstract: // Jian Yang 1, 2 * , Dong-Ming Zhu 1, 2 * , Xiao-Gang Zhou 1 * , Ni Yin 3 , Yi Zhang 1, 2 , Zi-Xiang Zhang 1, 2 , De-Chun Li 1, 2 and Jian Zhou 1, 2 1 Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China 2 Pancreatic Disease Research Center, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China 3 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China * Authors share co-first authorship Correspondence to: Jian Zhou, email: zhoujian06@suda.edu.cn Keywords: vasculogenic mimicry (VM), HIF-2α, Twist, VE-cadherin, pancreatic cancer Received: October 31, 2016 Accepted: February 02, 2017 Published: May 18, 2017 ABSTRACT Vasculogenic mimicry (VM) is a blood supply modality that occurs independently of endothelial cell angiogenesis. Hypoxia and the epithelial-mesenchymal transition (EMT) induce VM formation by remodeling the extracellular matrix. Our previous study demonstrated that hypoxia-inducible factor-2 alpha (HIF-2α) promotes the progress of EMT in pancreatic cancer; however, whether HIF-2α promotes VM formation in pancreatic cancer remains unknown. In this study, we investigated HIF-2α expression and VM by immunohistochemistry in 70 pancreatic cancer patients as well as the role of Twist1and Twist2 in HIF-2α-induced VM in vitro and in vivo . We found that the overexpression of HIF-2α and VM were correlated with poor tumor differentiation, late clinical stage and lymph node metastasis, and a poor prognosis in pancreatic cancer. Moreover, the upregulation of HIF-2α in SW1990 cells induced VM formation, whereas the opposite results were found after silencing HIF-2α in AsPC-1 cells. A mechanistic study indicated that HIF-2α might regulate the binding of twist1 to vascular endothelial cadherin (VE-cadherin) to promote VM formation in pancreatic cancer cells, and that the P1 (-421bp) and P4 (-2110bp) regions of the Twist1 binding sequences are positive regulatory elements for VE-cadherin. In addition, we confirmed that the overexpression of HIF-2α increased Twist1 expression and promoted tumor growth and VM formation in pancreatic cancer xenografts in nude mice. These findings indicated that HIF-2α might play a critical role in VM and that HIF-2α and the pathway of HIF-2α inducing VM formation are potential therapeutic targets for pancreatic cancer.
Published: 2017

36. Efficacy and safety of neoadjuvant FOLFIRINOX for borderline resectable pancreatic adenocarcinoma: improved efficacy compared with gemcitabine-based regimen

Author: Dong Wan Seo, Tae Jun Song, Jae Hoon Lee, Dae Wook Hwang, Sang Soo Lee, Jihoon Kang, Jin-Hong Park, Do Hyun Park, Sung Koo Lee, Baek-Yeol Ryoo, Kyu-Pyo Kim, Myung-Hwan Kim, Jae-Lyun Lee, Song Cheol Kim, Changhoon Yoo, Ki Byung Song, and Heung-Moon Chang
Subjects: Adult, Male, medicine.medical_specialty, FOLFIRINOX, medicine.medical_treatment, pancreatic cancer, Phases of clinical research, Adenocarcinoma, chemotherapy, Gastroenterology, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, Survival analysis, Aged, Neoplasm Staging, Chemotherapy, business.industry, neoadjuvant, Middle Aged, medicine.disease, Combined Modality Therapy, Survival Analysis, Gemcitabine, Surgery, Pancreatic Neoplasms, Regimen, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, business, Research Paper, medicine.drug
Abstract: Borderline resectable pancreatic cancer (BRPC) is a potentially resectable disease but is associated with poorer survival compared to primary resectable disease. There has been no prospective trial that compare the efficacy of FOLFIRNOX and gemcitabine-based regimen for BRPC. Between February 2013 and December 2014, 18 patients with BRPC receiving FOLFIRINOX were reviewed retrospectively. For comparative analysis, data for all BRPC patients (n=18) in our previous phase 2 study of neoadjuvant fixed-dose rate-gemcitabine plus capecitabine were pooled. Patients received a median 6 cycles (range, 3-13) of FOLFIRINOX. Surgical resection was performed in 12 patients (67%) and R0 resection in 9 patients. Median progression-free survival (PFS) and overall survival (OS) were 16.8 (95% confidence interval [CI], 9.4-24.2) and 21.2 (95% CI, 14.2-28.2) months, respectively. Patients who underwent surgical resection showed significantly better PFS (p=0.01) and OS (p=0.003) than those unresected. In the exploratory analysis, patients receiving FOLFIRINOX showed significantly longer PFS compared to those receiving fixed-dose rate-gemcitabine plus capecitabine (median 16.8 months [95% CI, 9.4-24.2] vs. 6.5 months [1.6-11.3]; p = 0.04). There was a trend toward improved OS in patients who received FOLFIRINOX (median 21.2 months [95% CI, 14.2-28.2]) compared to those who received fixed-dose rate-gemcitabine plus capecitabine (13.6 months [11.8-15.4]; p=0.12). FOLFIRINOX was feasible and effective as neoadjuvant chemotherapy for patients with BRPC and may have improved efficacy compared to a gemcitabine-based regimen.
Published: 2017

37. ADAM9 enhances CDCP1 by inhibiting miR-1 through EGFR signaling activation in lung cancer metastasis

Author: Yu Sen Lin, Chia Chien Lo, Hsien Fang Chang, Wei-Chung Cheng, Yen Nien Liu, Yuh Pyng Sher, Eric Y. Chuang, Kuo Liang Chiu, Ting Ting Kuo, Yu-Kai Huang, Ching Chan Lin, and Liang-Chuan Lai
Subjects: 0301 basic medicine, Gerontology, Oncology, Lung Neoplasms, CDCP1, Metastasis, Mice, Cell Movement, Medicine, Neoplasm Metastasis, 3' Untranslated Regions, Hematology, Prognosis, Neoplasm Proteins, ErbB Receptors, Gene Expression Regulation, Neoplastic, Disease Progression, Heterografts, RNA Interference, Signal Transduction, Research Paper, medicine.medical_specialty, ADAM9, EGFR, Medicine chest, Models, Biological, 03 medical and health sciences, Antigens, CD, Antigens, Neoplasm, Cell Line, Tumor, Internal medicine, microRNA, Animals, Humans, Lung cancer, business.industry, Membrane Proteins, Cancer, medicine.disease, Molecular medicine, miR-1, ADAM Proteins, Disease Models, Animal, MicroRNAs, lung cancer, 030104 developmental biology, business, Cell Adhesion Molecules, Biomedical sciences
Abstract: // Kuo-Liang Chiu 1, 4, 5, * , Yu-Sen Lin 1, 8, * , Ting-Ting Kuo 7 , Chia-Chien Lo 7 , Yu-Kai Huang 7 , Hsien-Fang Chang 6 , Eric Y. Chuang 6 , Ching-Chan Lin 1, 9 , Wei-Chung Cheng 2, 3 , Yen-Nien Liu 10 , Liang-Chuan Lai 6, 11 and Yuh-Pyng Sher 1, 2, 7 1 Graduate Institute of Clinical Medical Science, China Medical University, Taichung 404, Taiwan 2 Graduate Institute of BioMedical Sciences, China Medical University, Taichung 404, Taiwan 3 Research Center for Tumor Medical Science, China Medical University, Taichung 404, Taiwan 4 Division of Chest Medicine, Department of Internal Medicine, Taichung Tzu-Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, Taiwan 5 School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 970, Taiwan 6 Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei 100, Taiwan 7 Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan 8 Division of Thoracic Surgery, China Medical University Hospital, Taichung 404, Taiwan 9 Division of Hematology and Oncology, China Medical University Hospital, Taichung 404, Taiwan 10 Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan 11 Graduate Institute of Physiology, National Taiwan University, Taipei 106, Taiwan * These authors contributed equally to this work Correspondence to: Yuh-Pyng Sher, email: ypsher@mail.cmu.edu.tw Liang-Chuan Lai, email: llai@ntu.edu.tw Keywords: lung cancer, ADAM9, EGFR, miR-1, CDCP1 Received: November 30, 2016 Accepted: April 19, 2017 Published: May 07, 2017 ABSTRACT MicroRNAs (miRNAs), which are endogenous short noncoding RNAs, can regulate genes involved in important biological and pathological functions. Therefore, dysregulation of miRNAs plays a critical role in cancer progression. However, whether the aberrant expression of miRNAs is regulated by oncogenes remains unclear. We previously demonstrated that a disintegrin and metalloprotease domain 9 (ADAM9) promotes lung metastasis by enhancing the expression of a pro-migratory protein, CUB domain containing protein 1 (CDCP1). In this study, we found that this process occurred via miR-1 down-regulation. miR-1 expression was down-regulated in lung tumors, but increased in ADAM9 -knockdown lung cancer cells, and was negatively correlated with CDCP1 expression as well as the migration ability of lung cancer cells. Luciferase-based reporter assays showed that miR-1 directly bound to the 3′-untranslated region of CDCP1 and inhibited its translation. Treatment with a miR-1 inhibitor restored CDCP1 protein levels and enhanced tumor cell mobility. Overexpression of miR-1 decreased tumor metastases and increased the survival rate in mice. ADAM9 knockdown reduced EGFR signaling and increased miR-1 expression. These results revealed that ADAM9 down-regulates miR-1 via activating EGFR signaling pathways, which in turn enhances CDCP1 expression to promote lung cancer progression.
Published: 2017

38. EMT circulating tumor cells detected by cell-surface vimentin are associated with prostate cancer progression

Author: Shouhao Zhou, Izhar Singh Batth, Zachary Brownlee, Qing H. Meng, Abhishek Mitra, Shulin Li, Christina R. Rojas, Arun Satelli, Hyangsoon Noh, and Heming Li
Subjects: Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Pathology, Epithelial-Mesenchymal Transition, Colorectal cancer, epithelial mesenchymal transition, Vimentin, circulating tumor cells, castration resistance, 03 medical and health sciences, Prostate cancer, vimentin, 0302 clinical medicine, Circulating tumor cell, Cell Line, Tumor, Internal medicine, Biomarkers, Tumor, medicine, Humans, Epithelial–mesenchymal transition, Neoplasm Metastasis, Liquid biopsy, Aged, biology, business.industry, Cell Membrane, Prostatic Neoplasms, Cancer, Middle Aged, prostate cancer, Neoplastic Cells, Circulating, medicine.disease, 3. Good health, 030104 developmental biology, ROC Curve, Case-Control Studies, 030220 oncology & carcinogenesis, Disease Progression, biology.protein, Sarcoma, Neoplasm Grading, business, Research Paper
Abstract: // Arun Satelli 1, * , Izhar Batth 1, * , Zachary Brownlee 1 , Abhishek Mitra 1 , Shouhao Zhou 2 , Hyangsoon Noh 1 , Christina R. Rojas 1 , Heming Li 1 , Qing H. Meng 3 and Shulin Li 1 1 Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 3 Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA * These authors contributed equally to this work Correspondence to: Shulin Li, email: sli4@mdanderson.org Qing H. Meng, email: qhmeng@mdanderson.org Keywords: prostate cancer, epithelial mesenchymal transition, circulating tumor cells, vimentin, castration resistance Received: April 28, 2016 Accepted: April 21, 2017 Published: May 04, 2017 ABSTRACT Recent advances in the field of circulating tumor cells (CTC) have shown promise in this liquid biopsy-based prognosis of patient outcome. However, not all of the circulating cells are tumor cells, as evidenced by a lack of tumor-specific markers. The current FDA standard for capturing CTCs (CellSearch) relies on an epithelial marker and cells captured via CellSearch cannot be considered to have undergone EMT. Therefore, it is difficult to ascertain the presence and relevance of any mesenchymal or EMT-like CTCs. To address this gap in technology, we recently discovered the utility of cell-surface vimentin (CSV) as a marker for detecting mesenchymal CTCs from sarcoma, breast, and colon cancer. Here we studied peripheral blood samples of 48 prostate cancer (PCA) patients including hormone sensitive and castration resistant sub-groups. Blood samples were analyzed for three different properties including our own CSV-based CTC enumeration (using 84-1 mAb against CSV), CellSearch-based epithelial CTC counts, and serum prostate-specific antigen (PSA) quantification. Our data demonstrated that in comparison with CellSearch, the CSV-based method had greater sensitivity and specificity. Further, we observed significantly greater numbers of CTCs in castration resistant patients as measured by our CSV method but not CellSearch. Our data suggests CSV-guided CTC enumeration may hold prognostic value and should be further validated as a possible measurement of PCA progression towards the deadly, androgen-independent form.
Published: 2017

39. Sulfatase-1 overexpression indicates poor prognosis in urothelial carcinoma of the urinary bladder and upper tract

Author: Bi Wen Yeh, Wen-Jeng Wu, Chien-Feng Li, Peir In Liang, Hsin Chih Yeh, Chun Nung Huang, Wei-Ming Li, Kei Fu Yang, Hung Lung Ke, Yow-Ling Shiue, Hsiang-Ying Lee, Ti Chun Chan, and Ching Chia Li
Subjects: Male, 0301 basic medicine, Oncology, Gerontology, Urologic Neoplasms, medicine.medical_specialty, Poor prognosis, Gene Expression, Kaplan-Meier Estimate, Institute of medicine, SULF1, Heparan Sulfate Proteoglycans, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Neoplasm Metastasis, urothelial carcinoma, Aged, Cell Proliferation, Neoplasm Staging, Urothelial carcinoma, Aged, 80 and over, Urinary bladder, business.industry, Gene Expression Profiling, Middle Aged, Prognosis, University hospital, Survival Analysis, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, Urinary Bladder Neoplasms, Upper tract, 030220 oncology & carcinogenesis, Disease Progression, Female, Neoplasm Grading, Sulfatases, Sulfotransferases, Transcriptome, business, Research Paper, Biomedical sciences
Abstract: // Hsiang-Ying Lee 1, 3, 4, 8 , Bi-Wen Yeh 3, 4 , Ti-Chun Chan 5, 6 , Kei-Fu Yang 2, 3 , Wei-Ming Li 2, 3, 4, 7 , Chun-Nung Huang 3, 4 , Hung-Lung Ke 3, 4 , Ching-Chia Li 3, 4, 8 , Hsin-Chih Yeh 2, 3, 4, 7 , Peir-In Liang 9 , Yow-Ling Shiue 6 , Wen-Jeng Wu 2, 3, 4, 8, 10, 11, 12 and Chien-Feng Li 5, 9, 11, 13, 14, 15 1 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 4 Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan 6 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 7 Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan 8 Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan 9 Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 10 Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan 11 Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan 12 Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan 13 Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan 14 National Cancer Research Institute, National Health Research Institutes, Tainan, Taiwan 15 Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Correspondence to: Chien-Feng Li, email: angelo.p@yahoo.com.tw Wen-Jeng Wu, email: wejewu@kmu.edu.tw Keywords: urothelial carcinoma, transcriptome, SULF1, prognosis Received: November 25, 2016 Accepted: April 17, 2017 Published: May 03, 2017 ABSTRACT Urothelial carcinoma (UC), arising from the urothelium of the urinary tract, can occur in the upper (UTUC) and the urinary bladder (UBUC). A representative molecular aberration for UC characteristics and prognosis remains unclear. Data mining of Gene Expression Omnibus focusing on UBUC, we identified sulfatase-1 ( SULF1 ) upregulation is associated with UC progression. SULF1 controls the sulfation status of heparan sulfate proteoglycans and plays a role in tumor growth and metastasis, while its role is unexplored in UC. To first elucidate the clinical significance of SULF1 transcript expression, real-time quantitative RT-PCR was performed in a pilot study of 24 UTUC and 24 UBUC fresh samples. We identified that increased SULF1 transcript abundance was associated with higher primary tumor (pT) status. By testing SULF1 immunoexpression in independent UTUC and UBUC cohorts consisted of 340 and 295 cases, respectively, high SULF1 expression was significantly associated with advanced pT and nodal status, higher histological grade and presence of vascular invasion in both UTUC and UBUC. In multivariate survival analyses, high SULF1 expression was independently associated with worse DSS (UTUC hazard ratio [HR] = 3.574, P < 0.001; UBUC HR = 2.523, P = 0.011) and MeFS (UTUC HR = 3.233, P < 0.001; UBUC HR = 1.851, P = 0.021). Furthermore, depletion of SULF1 expression by using RNA interference leaded to impaired cell proliferative, migratory, and invasive abilities in vitro . In addition, we further confirmed oncogenic role of SULF1 with gain-of function experiments. In conclusion, our findings implicate the oncogenic role of SULF1 expression in UC, suggesting SULF1 as a prognostic and therapeutic target of UC.
Published: 2017

40. TRIB1 promotes colorectal cancer cell migration and invasion through activation MMP-2 via FAK/Src and ERK pathways

Author: Xiangning Meng, Donglin Sun, Jing Bai, Feng Chen, Haiming Sun, Chunyu Zhang, Bo Pang, Wenjing Sun, Jingshu Geng, Nan Wu, Yuhui Wang, Dandan Tong, Yan Jin, and Songbin Fu
Subjects: 0301 basic medicine, MAPK/ERK pathway, Male, Colorectal cancer, Gene Expression, migration, Metastasis, Ectopic Gene Expression, 0302 clinical medicine, Cell Movement, Medicine, Neoplasm Metastasis, MMP-2, TRIB1, Intracellular Signaling Peptides and Proteins, Cell migration, Middle Aged, invasion, src-Family Kinases, Oncology, 030220 oncology & carcinogenesis, Matrix Metalloproteinase 2, Female, Colorectal Neoplasms, Proto-oncogene tyrosine-protein kinase Src, Research Paper, Adult, MAP Kinase Signaling System, Protein Serine-Threonine Kinases, 03 medical and health sciences, colorectal carcinoma, Cell Line, Tumor, Cell Adhesion, Gene silencing, Humans, neoplasms, Aged, Cell Proliferation, Neoplasm Staging, Oncogene, business.industry, Gene Amplification, Cancer, medicine.disease, digestive system diseases, 030104 developmental biology, Focal Adhesion Kinase 1, Cancer research, Neoplasm Grading, business
Abstract: // Yuhui Wang 1, * , Nan Wu 1, * , Bo Pang 1, * , Dandan Tong 2 , Donglin Sun 1 , Haiming Sun 1 , Chunyu Zhang 1 , Wenjing Sun 1 , Xiangning Meng 1 , Jing Bai 1 , Feng Chen 1 , Jingshu Geng 3 , Songbin Fu 1, 4 and Yan Jin 1, 4 1 Laboratory of Medical Genetics, Harbin Medical University, Harbin, China 2 Department of Pathology, Harbin Medical University, Harbin, China 3 Department of Pathology, Third Affiliated Clinical Hospital, Harbin Medical University, Harbin, China 4 Key Laboratory of Medical Genetics, Harbin Medical University, Heilongjiang Higher Education Institutions, Harbin, China * These authors have contributed equally to this work Correspondence to: Yan Jin, email: jinyan@ems.hrbmu.edu.cn Songbin Fu, email: fusb@ems.hrbmu.edu.cn , fusongbin@yahoo.com Keywords: TRIB1, colorectal carcinoma, migration, invasion, MMP-2 Received: November 30, 2016 Accepted: May 01, 2017 Published: May 25, 2017 ABSTRACT Colorectal cancer (CRC) is the third most common cancer in the world and distant metastasis is the leading cause of death among CRC patients. However, the underlying mechanisms of distant metastasis remain largely unknown. Amplification of 8q24 is a common chromosomal abnormality in CRC. In the present study, a putative oncogene at 8q24, TRIB1, was characterized for its role in CRC metastasis and underlying molecular mechanisms. Higher expression of TRIB1 protein was detected in 58/83 (69.9%) of CRC tissues, compared with adjacent non-tumor tissues. Moreover, the expression of TRIB1 was significantly associated with distant metastasis ( P =0.043) and advanced staging ( P =0.008) in CRC tissues. TRIB1 overexpression was also correlated with poor prognosis in CRC patients as analyzed in PrognoScan database. In addition, elevated expression of TRIB1 promoted CRC cell motility and adhesive ability, while silencing of TRIB1 reduced those effects. Further study revealed that TRIB1-mediated migration and invasion of CRC cells required up-regulation of MMP-2 through the activation of FAK/Src and ERK pathway. Collectively, the results suggest that TRIB1 promotes CRC cell motility by activation MMP-2 via the FAK/Src and ERK pathways. It may provide a potential diagnostic and therapeutic target for CRC.
Published: 2017

41. Comparison of differentiated thyroid carcinoma recurrence and its clinical features in children of different ages

Author: Quan Wang, Longhao Wang, Jingrong Lü, Yan Ma, Bin Ye, Jun Shi, Chenling Shen, Mingliang Xiang, Haixia Hu, and Guangjun Yu
Subjects: Thyroid nodules, Male, medicine.medical_specialty, Pediatrics, recurrence, pediatrics, Adolescent, 030209 endocrinology & metabolism, Kaplan-Meier Estimate, Thyroid carcinoma, 03 medical and health sciences, Young Adult, 0302 clinical medicine, medicine, Humans, recurrence-free survival, Thyroid Neoplasms, Risk factor, Stage (cooking), Neoplasm Metastasis, Child, differentiated thyroid carcinoma, Neoplasm Staging, Retrospective Studies, Risk level, business.industry, Thyroid, Age Factors, medicine.disease, medicine.anatomical_structure, Oncology, Otorhinolaryngology, 030220 oncology & carcinogenesis, Child, Preschool, Head and neck surgery, Female, Neoplasm Grading, business, Research Paper
Abstract: // Bin Ye 1, * , Jun Shi 1, * , Chenling Shen 2, * , Longhao Wang 1 , Haixia Hu 1 , Yan Ma 1 , Quan Wang 1 , Jingrong Lu 1 , Guangjun Yu 2 and Mingliang Xiang 1 1 Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China 2 Shanghai Jiao Tong University School of Medicine, Shanghai, China * These authors have contributed equally to this work Correspondence to: Mingliang Xiang, email: mingliangxiang@163.com Guangjun Yu, email: Gjyu@shchildren.com.cn Jingrong Lu, email: lvjingrong@hotmail.com Keywords: differentiated thyroid carcinoma, recurrence, recurrence-free survival, pediatrics Abbreviations: ATA: American Thyroid Association; DTC: differentiated thyroid carcinoma; TNM: tumor-node-metastasis Received: January 02, 2017 Accepted: May 03, 2017 Published: May 26, 2017 ABSTRACT The prevalence of differentiated thyroid carcinoma (DTC) in children is increasing. However, the clinical features and recurrence of DTC in children in different age groups, especially those less than 14 years old, are not well studied. We retrospectively investigated 73 children diagnosed with DTC in our hospital between January 1998 and July 2014. Data were reviewed for different age groups based on the age at initial diagnosis: 5-9, 10-14, or 15-19 years. The mean age of the recurrence group (10.6±4.1 years) was lower than that of the non-recurrence group (12.6±6.2 years; P =0.004). The main symptom at initial diagnosis was local invasion in the recurrence group, but was thyroid nodules in the non-recurrence group ( P
Published: 2017

42. Elevated CRP levels predict poor outcome and tumor recurrence in patients with thymic epithelial tumors: A pro- and retrospective analysis

Author: Bernhard Moser, Lucian Beer, Christine Bekos, Elisa Einwallner, Philipp Hacker, Walter Klepetko, Thomas Raunegger, Leonhard Müllauer, Hendrik Jan Ankersmit, Bahil Ghanim, and Stefan Janik
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Pathology, Thymoma, thymic epithelial tumors, Neuroendocrine tumors, Gastroenterology, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Myasthenia Gravis, Biomarkers, Tumor, medicine, Humans, Clinical significance, Neoplasms, Glandular and Epithelial, Neoplasm Metastasis, Thymic carcinoma, Aged, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, business.industry, Reproducibility of Results, Interleukin, Thymus Neoplasms, thymoma, Middle Aged, Prognosis, medicine.disease, humanities, C-Reactive Protein, 030104 developmental biology, Oncology, Cardiothoracic surgery, Case-Control Studies, 030220 oncology & carcinogenesis, Immunohistochemistry, Female, Neoplasm Recurrence, Local, thymic carcinoma, CRP, business, Research Paper, Follow-Up Studies
Abstract: // Stefan Janik 1, 2 , Christine Bekos 1, 2 , Philipp Hacker 1, 2 , Thomas Raunegger 1, 2 , Bahil Ghanim 1 , Elisa Einwallner 3 , Lucian Beer 2, 4 , Walter Klepetko 1 , Leonhard Mullauer 5 , Hendrik J. Ankersmit 1, 2 and Bernhard Moser 1 1 Department of Thoracic Surgery, Division of Surgery, Medical University of Vienna, Vienna, Austria 2 Christian Doppler Laboratory for Diagnosis and Regeneration of Cardiac and Thoracic Diseases, Medical University of Vienna, Vienna, Austria 3 Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria 4 Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria 5 Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria Correspondence to: Bernhard Moser, email: bernhard.moser@meduniwien.ac.at Keywords: thymic epithelial tumors, thymoma, thymic carcinoma, CRP, prognosis Received: November 11, 2016 Accepted: April 12, 2017 Published: April 27, 2017 ABSTRACT Objective: Scarce information exists on the pathogenesis of thymic epithelial tumors (TETs), comprising thymomas, thymic carcinomas (TCs) and neuroendocrine tumors. C-reactive protein (CRP) increases during certain malignancies. We aimed to investigate the clinical relevance of CRP in patients with TETs. Results: Pretreatment CRP serum concentrations were significantly elevated in patients with TETs, particularly TCs and metastatic TETs. After complete tumor resection CRP serum concentrations were decreased ( p = 0.135) but increased significantly in case of tumor recurrence ( p = 0.001). High pretreatment CRP was associated with significantly worse 5- and 10-year freedom-from recurrence (FFR) ( p = 0.010) and was a negative prognostic factor for FFR (HR 3.30; p = 0.015). IL-6 (not IL-1β) serum concentrations were significantly elevated in patients with TETs but we did not detect CRP tissue expression in TETs. Materials and Methods: Pretreatment CRP serum concentrations were retrospectively analyzed from 128 surgical patients (1990–2015). In a subset of 68 patients longitudinal analysis of CRP was performed. Additionally, immunohistochemical tumor CRP expression and serum concentrations of interleukin (IL)-6 and IL-1β were measured. Conclusions: Hence, diagnostic measurement of serum CRP might be useful to indicate highly aggressive TETs and to make doctors consider tumor recurrences during oncological follow-up.
Published: 2017

43. Microwave ablation combined with attenuated Salmonella typhimurium for treating hepatocellular carcinoma in a rat model

Author: Qing Zhao, Rong Liu, Xu-Dong Qu, Jian-Hua Wang, Bo Zhou, Guowei Yang, Kai Liu, Huibin Shi, Zhiping Yan, Sheng Qian, Wei Zhang, and Liang Zhu
Subjects: Ablation Techniques, Male, Salmonella typhimurium, 0301 basic medicine, medicine.medical_specialty, Salmonella, Carcinoma, Hepatocellular, Rat model, Urology, Apoptosis, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, medicine, Animals, Neoplasm Metastasis, Microwaves, Cell Proliferation, Lung, medicine.diagnostic_test, business.industry, Liver Neoplasms, Microwave ablation, Magnetic resonance imaging, hepatocellular carcinoma, medicine.disease, Combined Modality Therapy, Magnetic Resonance Imaging, Xenograft Model Antitumor Assays, Rats, Surgery, Disease Models, Animal, Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, Oncology, microwave ablation, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Immunohistochemistry, VNP 20009, business, Biomarkers, Research Paper
Abstract: We aim to investigate the safety and efficacy of microwave ablation (MWA) combined with attenuated Salmonella typhimurium strain VNP20009 in treating hepatocellular carcinoma. Portions of tumor tissues were orthotopically implanted in the livers of 40 male rats weighed 150~200 g to establish tumor models. Three weeks later, the rats were randomly divided into four groups: (A) MWA plus VNP20009 group; (B) MWA group; (C) VNP20009 group; and (D) control group. Incomplete MWA was performed (20~30 W, 1~2 min) after the hepatic carcinoma was properly exposed. VNP20009 (about 1×107 cfu) was directly injected into the tumor immediately. MRI scans were performed to assess the tumor responses 7 and 14 days later, respectively. Micro CT was used to observe the lung metastases. After the animals were sacrificed or died, the tumors were cut off for the purpose of pathological and immunohistochemical analyses. The results showed that the mean tumor volumes of MWA plus VNP20009 group on the 7th and 14th day post treatment were obviously smaller than those of other groups (P < 0.05). Lung metastases rates were 20%, 60%, 30% and 100% in MWA plus VNP20009 group, MWA group, VNP20009 group and control group, respectively. The median survival of the rats in MWA plus VNP20009 group was distinctly longer than those in other groups (P < 0.05). In summary, MWA combined with VNP20009 produced better effects than MWA or VNP20009 alone in treating hepatic carcinoma. This strategy might have potential ability to decrease lung metastases and prolong the overall survival.
Published: 2017

44. Gene expression signature of Gleason score is associated with prostate cancer outcomes in a radical prostatectomy cohort

Author: Min A. Jhun, Janet L. Stanford, Craig April, Jian-Bing Fan, Ziding Feng, Jonathan L. Wright, Marina Bibikova, Elaine A. Ostrander, Milan S. Geybels, Suzanne Kolb, Epidemiologie, and RS: GROW - R1 - Prevention
Subjects: Male, 0301 basic medicine, Oncology, Pathology, medicine.medical_treatment, PROGRESSION, RISK STRATIFICATION, Metastasis, Cohort Studies, Prostate cancer, 0302 clinical medicine, METASTATIC-DISEASE, Epidemiology, BIOCHEMICAL RECURRENCE, Neoplasm Metastasis, POPULATION, education.field_of_study, Prostatectomy, DEATH, Middle Aged, Prognosis, prostate cancer, NEEDLE-BIOPSY COHORT, 3. Good health, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Disease Progression, Research Paper, Biochemical recurrence, medicine.medical_specialty, recurrence, CARCINOMA, Population, GENOMIC CLASSIFIER, VALIDATION, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Humans, metastasis, Gleason score, education, Aged, Neoplasm Staging, Proportional Hazards Models, Proportional hazards model, business.industry, Gene Expression Profiling, Prostatic Neoplasms, medicine.disease, Gene expression profiling, 030104 developmental biology, gene expression, Neoplasm Grading, Transcriptome, business, Follow-Up Studies
Abstract: // Min A. Jhun 1 , Milan S. Geybels 1, 2 , Jonathan L. Wright 1, 3 , Suzanne Kolb 1 , Craig April 4 , Marina Bibikova 4 , Elaine A. Ostrander 5 , Jian-Bing Fan 4 , Ziding Feng 6 and Janet L. Stanford 1, 7 1 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 2 Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands 3 Department of Urology, University of Washington School of Medicine, Seattle, WA, USA 4 Department of Oncology, Illumina, Inc., San Diego, CA, USA 5 Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA 6 Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA 7 Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA Correspondence to: Janet L. Stanford, email: jstanfor@fredhutch.org Keywords: gene expression, Gleason score, prostate cancer, recurrence, metastasis Received: February 17, 2017 Accepted: March 30, 2017 Published: April 26, 2017 ABSTRACT Prostate cancer (PCa) is a leading cause of cancer-related mortality worldwide. Gleason score (GS) is one of the best predictors of PCa aggressiveness, but additional tumor biomarkers may improve its prognostic accuracy. We developed a gene expression signature of GS to enhance the prediction of PCa outcomes. Elastic net was used to construct a gene expression signature by contrasting GS 8-10 vs. ≤6 tumors in The Cancer Genome Atlas (TCGA) dataset. The constructed signature was then evaluated for its ability to predict recurrence and metastatic-lethal (ML) progression in a Fred Hutchinson (FH) patient cohort (N=408; N Recurrence =109; N MLprogression =27). The expression signature included transcripts representing 49 genes. In the FH cohort, a 25% increase in the signature was associated with a hazard ratio (HR) of 1.51 (P=2.7×10 −5 ) for recurrence. The signature’s area under the curve (AUC) for predicting recurrence and ML progression was 0.68 and 0.76, respectively. Compared to a model with age at diagnosis, pathological stage and GS, the gene expression signature improved the AUC for recurrence (3%) and ML progression (6%). Higher levels of the signature were associated with increased expression of genes in cell cycle-related pathways and decreased expression of genes in androgen response, estrogen response, oxidative phosphorylation, and apoptosis. This gene expression signature based on GS may improve the prediction of recurrence as well as ML progression in PCa patients after radical prostatectomy.
Published: 2017

45. Dual-negative expression of Nrf2 and NQO1 predicts superior outcomes in patients with non-small cell lung cancer

Author: Youyou Yan, Ying-Hui Tong, Jia-Wen Yu, Dan Su, Neng-Ming Lin, Luo Fang, Bo Zhang, Si-Si Kong, Dan Zhang, and Yun Fan
Subjects: Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Pathology, Lung Neoplasms, NF-E2-Related Factor 2, Gene Expression, non-small cell lung cancer (NSCLC), Kaplan-Meier Estimate, digestive system, environment and public health, NF-E2-related factor 2 (Nrf2), 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Internal medicine, Thoracic Oncology, Biomarkers, Tumor, NAD(P)H Dehydrogenase (Quinone), medicine, Humans, dual-negative expression, Neoplasm Metastasis, Esophagus, Lung cancer, Neoplasm Staging, Proportional Hazards Models, Lung, business.industry, Proportional hazards model, Cancer, respiratory system, Prognosis, medicine.disease, Immunohistochemistry, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, NAD(P)H quinone oxidoreductase-1 (NQO1), Female, business, Research Paper
Abstract: // Ying-Hui Tong 1, * , Bo Zhang 2, * , You-You Yan 2 , Yun Fan 3 , Jia-Wen Yu 1 , Si-Si Kong 1 , Dan Zhang 2 , Luo Fang 1 , Dan Su 3 and Neng-Ming Lin 2 1 Laboratory of Clinical Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China 2 Laboratory of Clinical Pharmacology, Translational Medicine Research Center, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou, Zhejiang 310006, China 3 Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology (Esophagus, Lung), Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China * These authors have contributed equally to this work Correspondence to: Neng-Ming Lin, email: lnm1013@163.com Keywords: non-small cell lung cancer (NSCLC), NF-E2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase-1 (NQO1), prognosis, dual-negative expression Received: January 12, 2017 Accepted: April 03, 2017 Published: April 25, 2017 ABSTRACT Functional studies in non-small cell lung cancer (NSCLC) patients revealed that hyperactivation of the NF-E2-related factor 2 (Nrf2) pathway facilitates tumor growth. We examined the usefulness of Nrf2 and NQO1 as indicators of prognosis in NSCLC. Tumor and adjacent non-tumor tissue samples were collected from 215 NSCLC patients who had tumor resections between 2006 and 2011. Immunohistochemistry was performed to detect Nrf2 or NQO1 expression. The correlation between Nrf2 or NQO1 expression and survival outcomes was evaluated using the Kaplan-Meier method and Cox proportional hazards regression model. Levels of Nrf2 and NQO1 were elevated in tumor tissues. In particular, Nrf2 was elevated in nearly all tumor cells. NQO1 expression positively correlated with Nrf2 expression ( P = 0.039). Nrf2 expression positively correlated with lymph node metastasis ( P = 0.001) and negatively correlated with tumor differentiation ( P = 0.032). As compared with either Nrf2 or NQO1 alone, dual-negative expression of Nrf2 and NQO1 was more predictive of superior overall survival ( P = 0.020) and disease free survival ( P = 0.037). Subgroup analyses showed that females, nonsmokers, and patients with advanced-stage NSCLC were suitable populations in which to evaluate prognosis based on Nrf2 and NQO1 co-expression. These results indicate that dual-negative expression of Nrf2 and NQO1 is predictive of a better prognosis in NSCLC patients.
Published: 2017

46. miR-551b regulates epithelial-mesenchymal transition and metastasis of gastric cancer by inhibiting ERBB4 expression

Author: Guangyuan Song, Ji Shi, Lijie Gong, Biao Chen, Shaoyun Zhao, Hongcheng Zhang, Ji Xu, Zaiyuan Ye, and Chenlin Chen
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Receptor, ErbB-4, Vimentin, miR-551b, Metastasis, Transforming Growth Factor beta1, Mice, 03 medical and health sciences, 0302 clinical medicine, Western blot, Downregulation and upregulation, Cell Movement, Stomach Neoplasms, Cell Line, Tumor, medicine, metastasis, Animals, Humans, Epithelial–mesenchymal transition, Neoplasm Metastasis, 3' Untranslated Regions, ERBB4, Neoplasm Staging, medicine.diagnostic_test, biology, business.industry, gastric cancer, Gene Expression Profiling, Cancer, Prognosis, medicine.disease, Gene Expression Regulation, Neoplastic, epithelial-mesenchymal transition (EMT), Disease Models, Animal, MicroRNAs, 030104 developmental biology, Oncology, Cell culture, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, biology.protein, Heterografts, RNA Interference, business, Research Paper
Abstract: // Guangyuan Song 1, * , Hongcheng Zhang 1, * , Chenlin Chen 1 , Lijie Gong 1 , Biao Chen 1 , Shaoyun Zhao 1 , Ji Shi 2 , Ji Xu 3, 4 and Zaiyuan Ye 3, 4 1 The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China 2 The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China 3 Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, China 4 Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, Zhejiang, China * These authors contributed equally to this work and are co-first authors. Correspondence to: Ji Xu, email: xuji120@163.com Zaiyuan Ye, email: zaiyuanye@163.com Keywords: miR-551b, epithelial-mesenchymal transition (EMT), metastasis, gastric cancer, ERBB4 Received: December 05, 2016 Accepted: April 02, 2017 Published: April 24, 2017 ABSTRACT Epithelial-mesenchymal transition (EMT) is an important biological process that is characteristic of malignant tumor cells with metastatic potential. We investigated the role of miR-551b in EMT and metastasis in gastric cancer (GC). We found that low miR-551b levels were associated with EMT, metastasis and a poor prognosis in GC patients. Further, two GC cell lines, MNK45 and SGC7901, exhibited lower miR-551b levels than the GES normal stomach cell line. Exposing MNK45 and SGC7901 cells to TGF-β1 resulted in cell morphology changes characteristic of EMT, which was confirmed by Western blot analysis demonstrating low E-Cadherin and high N-Cadherin and Vimentin levels. Treatment with miR-551b mimics inhibited these EMT changes as well as Transwell migration and invasiveness. We identified ERBB4 as a potential target of miR-551b based on patient data from the TCGA. ERBB4 was upregulated in GC specimens, and its high expression correlated with a poor prognosis of GC patients. Dual luciferase assays revealed that miR-551b directly inhibited ERBB4 by binding to its 3’UTR. Moreover, treatment with miR-551b mimics or the ERBB4 inhibitor AST-1306 inhibited EMT in the GC cell lines. Finally, nude mice xenografted with GC cancer cell lines expressing miR-551b mimics exhibited smaller tumors and longer survival than mice engrafted with control GC cancer cells. These data indicate that miR-551b inhibits EMT and metastasis in GC by inhibiting ERBB4. miR-551b and ERBB4 are thus potential therapeutic targets for the treatment of GC.
Published: 2017

47. 18F-fluorodeoxyglucose uptake predicts PKM2 expression in lung adenocarcinoma

Author: Xiang Zhao, Guangyu Hu, Weiyuan Xiao, Yuqi Dong, and Ping Huang
Subjects: Male, 0301 basic medicine, Pathology, Lung Neoplasms, Gastroenterology, 0302 clinical medicine, Positron Emission Tomography Computed Tomography, Neoplasm Metastasis, lung adenocarcinomas, Aged, 80 and over, medicine.diagnostic_test, glycolysis, Middle Aged, Prognosis, Primary tumor, Survival Rate, medicine.anatomical_structure, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, PKM2, Research Paper, medicine.drug, Adult, Thyroid Hormones, medicine.medical_specialty, Standardized uptake value, 18F-FDG uptake, 03 medical and health sciences, Fluorodeoxyglucose F18, Internal medicine, Biomarkers, Tumor, medicine, Humans, Survival rate, Aged, Retrospective Studies, Fluorodeoxyglucose, Lung, business.industry, Membrane Proteins, medicine.disease, 030104 developmental biology, Radiopharmaceuticals, Carrier Proteins, business, Follow-Up Studies
Abstract: // Ping Huang 1, * , Xiang Zhao 1, * , Weiyuan Xiao 1 , Yuqi Dong 1 and Guangyu Hu 1 1 Department of Orthopaedics, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Guangyu Hu, email: huguangyu160@126.com Yuqi Dong, email: dyqrjgk@126.com Keywords: lung adenocarcinomas, PKM2, glycolysis, 18 F-FDG uptake Received: November 01, 2016 Accepted: March 29, 2017 Published: April 24, 2017 ABSTRACT Positron emission tomography (PET) with 18 F-fluorodeoxyglucose ( 18 F-FDG) is widely used in the management of lung adenocarcinoma. Pyruvate kinase M2 (PKM2) plays a key role in glycolysis. We therefore investigated whether PKM2 expression affects 18 F-FDG uptake in a retrospective analysis of 76 patients who underwent 18 F-FDG PET/computed tomography (CT) scans for staging before surgical resection. We found that PKM2 expression was higher in tumors than peritumoral tissue (p < 0.05). Patients with high PKM2 expression had reduced overall (p < 0.05) and disease-free (p < 0.05) survival as compared to those with low PKM2 expression. Comparison of the primary tumor maximum standardized uptake value (SUVmax) between patients with high and low PKM2 expression revealed that the SUVmax was higher in primary tumors with high PKM2 expression than low PKM2 expression (p < 0.05). Multivariate analysis confirmed the association between SUVmax and PKM2 expression (p < 0.05). PKM2 status was predicted with 81.6% accuracy when the SUVmax cutoff value of 6.4. Thus, 18 F-FDG PET/CT is predictive of the PKM2 status in lung adenocarcinoma patients and could aid in determining therapeutic strategies.
Published: 2017

48. Increased S100A15 expression and decreased DNA methylation of its gene promoter are involved in high metastasis potential and poor outcome of lung adenocarcinoma

Author: Yung-Che Chen, Yu-Mu Chen, Kuang-Den Chen, Ming-Tse Sung, Meng-Chih Lin, Ting-Ya Wang, Chung-Jen Chen, Chang-Chun Hsiao, Yi-Xin Zheng, Jen-Chieh Chang, Huang-Chih Chang, and Yong-Yong Lin
Subjects: Male, 0301 basic medicine, Oncology, Pathology, Lung Neoplasms, S100 Calcium Binding Protein A7, Metastasis, 0302 clinical medicine, Cell Movement, Antineoplastic Combined Chemotherapy Protocols, Molecular Targeted Therapy, Neoplasm Metastasis, Promoter Regions, Genetic, next generation sequencing, DNA methylation, biology, S100 Proteins, Methylation, Middle Aged, Prognosis, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, Research Paper, medicine.medical_specialty, Adenocarcinoma of Lung, 03 medical and health sciences, Cell Line, Tumor, Internal medicine, medicine, Humans, Lung cancer, Aged, Cell Proliferation, Neoplasm Staging, business.industry, Gene Expression Profiling, Promoter, lung adenocarcinoma, medicine.disease, Proliferating cell nuclear antigen, S100A15, 030104 developmental biology, biology.protein, CpG Islands, business
Abstract: // Yung-Che Chen 1, 6, * , Meng-Chih Lin 1, 6, * , Chang-Chun Hsiao 6, 7 , Yi-Xin Zheng 1 , Kuang-Den Chen 2 , Ming-Tse Sung 3 , Chung-Jen Chen 4 , Ting-Ya Wang 1 , Yong-Yong Lin 1 , Huang-Chih Chang 1, 6 , Yu-Mu Chen 1 and Jen-Chieh Chang 5 1 Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Center of Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 4 Division of Rheumatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan 7 Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Yung-Che Chen, email: yungchechen@yahoo.com.tw Meng-Chih Lin, email: linmengchih@hotmail.com Chang-Chun Hsiao, email: cchsiao@mail.cgu.edu.tw Keywords: lung adenocarcinoma, S100A15, DNA methylation, next generation sequencing Received: November 02, 2016 Accepted: April 10, 2017 Published: April 24, 2017 ABSTRACT Purpose : This study aims to determine the functional role of S100A15 and its promoter DNA methylation patterns in lung cancer progression. Experimental Design : We analyzed 178 formalin-fixed paraffin embedded specimens from lung cancer patients, including 24 early stage and 91 advanced stage adenocarcinoma. S100A15 protein expression was evaluated by immunohistochemistry stain, and its DNA methylation levels were measured by pyrosequencing. Results : S100A15 nuclear staining was increased in lung adenocarcinoma patients with distant metastasis versus those without distant metastasis. There was reduced one/three-year overall survival in adenocarcinoma patients receiving first line target therapy and harboring high nuclear expressions of S100A15. Both DNA methylation levels over -423 and -248 CpG sites of the S100A15 gene promoter were decreased in adenocarcinoma patients with distant metastasis, and the former was associated with lower one-year overall survival. The highly invasive CL1-5 cell lines display decreased DNA methylation over –412/-248/-56 CpG sites of the S100A15 gene promoter and increased S100A15 gene/protein expressions as compared with the less invasive CL1-0 cell lines. Knockdown of S100A15 in CL1-5 cell line inhibited cell proliferation, migration, and invasion, while over-expression of S100A15 in CL1-0 cell line promoted cell proliferation, migration, and invasion. RNA sequencing analysis revealed potential biological effects of S100A15 over-expression and knock-down with CTNNB1, ZEB1, CDC42, HSP90AA1, BST2, and PCNA being the pivotal down-stream mediators. Conclusions : Increased S100A15 expression and decreased DNA methylation of its gene promoter region were associated with high metastasis potential and poor outcome in lung adenocarcinoma, probably through triggering CTNNB1 -centered pathways.
Published: 2017

49. POU2F1 over-expression correlates with poor prognoses and promotes cell growth and epithelial-to-mesenchymal transition in hepatocellular carcinoma

Author: Guang-Rong Yan, Hongyang Huang, Qing-Xia Wu, Yonghao Zhong, Jin-Zhou Huang, Min Chen, and De Chen
Subjects: Adult, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, Gene Expression, medicine.disease_cause, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, medicine, Humans, Gene Silencing, Epithelial–mesenchymal transition, Neoplasm Metastasis, Protein kinase B, PI3K/AKT/mTOR pathway, Aged, Cell Proliferation, Proportional Hazards Models, business.industry, Liver Neoplasms, hepatocellular carcinoma, Middle Aged, POU2F1, Prognosis, medicine.disease, digestive system diseases, Tumor Burden, SNAI2, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, SNAI1, Cancer research, Female, Neoplasm Grading, Carcinogenesis, business, Proto-Oncogene Proteins c-akt, Octamer Transcription Factor-1, Research Paper
Abstract: // Yonghao Zhong 1, 2, * , Hongyang Huang 1, 2, * , Min Chen 1 , Jinzhou Huang 1 , Qingxia Wu 1 , Guang-Rong Yan 1, 3 and De Chen 1, 2, 3 1 Biomedicine Research Center, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 2 Department of Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 3 Key Laboratory of Protein Modification and Degradation, Guangzhou Medical University, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Guang-Rong Yan, email: jxygr007@yahoo.com De Chen, email: drchende@gzhmu.edu.cn Keywords: POU2F1, hepatocellular carcinoma Abbreviations: POU2F1, POU domain class 2 transcription factor 1; HCC, hepatocellular carcinoma; EMT, epithelial-to-mesenchymal transition; OS, overall survival Received: November 11, 2016 Accepted: April 03, 2017 Published: April 20, 2017 ABSTRACT Despite recent efforts to understand activities of POU domain class 2 transcription factor 1 (POU2F1), little is known about the roles of POU2F1 in hepatocellular carcinoma (HCC) tumorigenesis and its correlation with any clinicopathological feature of HCC. In this study, we found that POU2F1 was significantly up-regulated in HCC specimens compared with adjacent non-cancerous liver specimens. The high POU2F1 protein expression level positively correlated with large tumor size, high histological grade, tumor metastasis and advanced clinical stage, and HCC patients with high POU2F1 levels exhibited poor prognoses. We further demonstrated that POU2F1 over-expression promoted HCC cell proliferation, colony formation, epithelial-to-mesenchymal transition (EMT), migration and invasion, while silencing of POU2F1 inhibited these malignant phenotypes. POU2F1 induced the expression of Twist1 , Snai1 , Snai2 and ZEB1 genes which are involved in the regulation of EMT. Furthermore, POU2F1 was up-regulated by AKT pathway in HCC, and POU2F1 over-expression reversed the inhibition of malignant phenotypes induced by AKT knock-down, indicating POU2F1 is a key down-stream effector of AKT pathway. Collectively, our results indicate that POU2F1 over-expression is positively associated with aggressive phenotypes and poor survival in patients with HCC, and POU2F1 regulated by AKT pathway promotes HCC aggressive phenotypes by regulating the transcription of EMT genes. POU2F1 may be employed as a new prognostic factor and therapeutic target for HCC.
Published: 2017

50. Lymph nodes ratio based nomogram predicts survival of resectable gastric cancer regardless of the number of examined lymph nodes

Author: Jing Guo, Shangxiang Chen, Shun Li, Qirong Geng, Pengfei Kong, Xuechao Liu, Youqing Zhan, Xiaowei Sun, Dazhi Xu, Jianjun Liu, and Huamin Rao
Subjects: Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Breast surgery, medicine.medical_treatment, nomogram, Young Adult, 03 medical and health sciences, lymph nodes ratio, 0302 clinical medicine, Gastrectomy, Risk Factors, Stomach Neoplasms, Internal medicine, Epidemiology, Humans, Medicine, Neoplasm Metastasis, Aged, Neoplasm Staging, Aged, 80 and over, business.industry, Proportional hazards model, gastric cancer, curative resection, Reproducibility of Results, Cancer, Middle Aged, Nomogram, Prognosis, medicine.disease, Tumor Burden, Surgery, Nomograms, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, Lymph Nodes, Lymph, business, Follow-Up Studies, Research Paper, Abdominal surgery
Abstract: // Shangxiang Chen 1, 5, * , Huamin Rao 2, * , Jianjun Liu 3, * , Qirong Geng 1, 4, * , Jing Guo 1, 5 , Pengfei Kong 1, 5 , Shun Li 1, 5 , Xuechao Liu 1, 5 , Xiaowei Sun 1, 5 , Youqing Zhan 1, 5 and Dazhi Xu 1, 5,* 1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 2 Department of Abdominal Surgery, Jiangxi Cancer Hospital, Nanchang, China 3 Department of Breast Surgery, Anhui Provincial Cancer Hospital, West Branch of Anhui Provincial Hospital, Hefei, China 4 Department of Hematology Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China 5 Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Dazhi Xu, email: xudzh@sysucc.org.cn Keywords: nomogram, gastric cancer, curative resection, lymph nodes ratio, prognosis Received: February 18, 2017 Accepted: March 27, 2017 Published: April 20, 2017 ABSTRACT To develop a nomogram to predict the prognosis of gastric cancer patients on the basis of metastatic lymph nodes ratio (mLNR), especially in the patients with total number of examined lymph nodes (TLN) less than 15. The nomogram was constructed based on a retrospective database that included 2,205 patients underwent curative resection in Cancer Center, Sun Yat-sen University (SYSUCC). Resectable gastric cancer (RGC) patients underwent curative resection before December 31, 2008 were assigned as the training set (n=1,470) and those between January 1, 2009 and December 31, 2012 were selected as the internal validation set (n=735). Additional external validations were also performed separately by an independent data set (n=602) from Jiangxi Provincial Cancer Hospital (JXCH) in Jiangxi, China and a data set (n=3,317) from the Surveillance, Epidemiology, and End Results (SEER) database. The Independent risk factors were identified by Multivariate Cox Regression. In the SYSUCC set, TNM (Tumor-node-metastasis) and TRM-based (Tumor-Positive Nodes Ratio-Metastasis) nomograms were constructed respectively. The TNM-based nomogram showed better discrimination than the AJCC-TNM staging system (C-index: 0.73 versus 0.69, p
Published: 2017

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Region

Database

Publisher

1,879 results on '"Neoplasm metastasis"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources