99 results on '"Chen, Yan"'
Search Results
2. Rare subclonal sequencing of breast cancers indicates putative metastatic driver mutations are predominately acquired after dissemination
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Lawrence-Paul, Matthew R., Pan, Tien-chi, Pant, Dhruv K., Shih, Natalie N. C., Chen, Yan, Belka, George K., Feldman, Michael, DeMichele, Angela, and Chodosh, Lewis A.
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- 2024
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3. The lncRNA NEAT1 promotes the epithelial-mesenchymal transition and metastasis of osteosarcoma cells by sponging miR-483 to upregulate STAT3 expression
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Chen, Yan, Li, Jun, Xiao, Jia-Kun, Xiao, Lei, Xu, Bin-Wu, and Li, Chen
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- 2021
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4. Nitric oxide-releasing micelles with intelligent targeting for enhanced anti-tumor effect of cisplatin in hypoxia
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Chen, Yan, Fang, Lei, Zhou, Weixin, Chang, Jinghan, Zhang, Xiaojuan, He, Chuanchuan, Chen, Chen, Yan, Ruicong, Yan, Yakai, Lu, Yao, Xu, Chuanrui, and Xiang, Guangya
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- 2021
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5. Circ-ASH2L promotes tumor progression by sponging miR-34a to regulate Notch1 in pancreatic ductal adenocarcinoma
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Chen, Yan, Li, Zhonghu, Zhang, Mengyun, Wang, Bo, Ye, Jiaxin, Zhang, Yang, Tang, Di, Ma, Dandan, Jin, Weidong, Li, Xiaowu, and Wang, Shuguang
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- 2019
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6. The liver microenvironment orchestrates FGL1-mediated immune escape and progression of metastatic colorectal cancer.
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Li, Jia-Jun, Wang, Jin-Hong, Tian, Tian, Liu, Jia, Zheng, Yong-Qiang, Mo, Hai-Yu, Sheng, Hui, Chen, Yan-Xing, Wu, Qi-Nian, Han, Yi, Liao, Kun, Pan, Yi-Qian, Zeng, Zhao-Lei, Liu, Ze-Xian, Yang, Wei, Xu, Rui-Hua, and Ju, Huai-Qiang
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COLORECTAL cancer ,METASTASIS ,LIVER metastasis ,CANCER invasiveness ,LIVER ,T cells ,CETUXIMAB - Abstract
Colorectal cancer (CRC) patients with liver metastases usually obtain less benefit from immunotherapy, and the underlying mechanisms remain understudied. Here, we identify that fibrinogen-like protein 1 (FGL1), secreted from cancer cells and hepatocytes, facilitates the progression of CRC in an intraportal injection model by reducing the infiltration of T cells. Mechanistically, tumor-associated macrophages (TAMs) activate NF-ĸB by secreting TNFα/IL-1β in the liver microenvironment and transcriptionally upregulate OTU deubiquitinase 1 (OTUD1) expression, which enhances FGL1 stability via deubiquitination. Disrupting the TAM-OTUD1-FGL1 axis inhibits metastatic tumor progression and synergizes with immune checkpoint blockade (ICB) therapy. Clinically, high plasma FGL1 levels predict poor outcomes and reduced ICB therapy benefits. Benzethonium chloride, an FDA-approved antiseptics, curbs FGL1 secretion, thereby inhibiting liver metastatic tumor growth. Overall, this study uncovers the critical roles and posttranslational regulatory mechanism of FGL1 in promoting metastatic tumor progression, highlighting the TAM-OTUD1-FGL1 axis as a potential target for cancer immunotherapy. The suppressive immune microenvironment in colorectal cancer (CRC) liver metastasis remains to be explored. Here, the authors find tumor-associated macrophages in the liver microenvironment induces elevated secretion of FGL1 from cancer cells and hepatocytes which promotes CRC metastasis by suppressing the infiltration of T cells. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Differential diagnosis of adrenal adenomas and metastases using spectral parameters in dual-layer detector spectral CT.
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Wu, Lei-di, Yue, Xiao-fei, Wu, Lin-xia, Yang, Ming, Chen, Yan, Yu, Jie, Diao, Nan, Zhang, Xiao-hui, Zhu, Liang-ru, and Han, Ping
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ADENOMA ,DIFFERENTIAL diagnosis ,RECEIVER operating characteristic curves ,METASTASIS ,DETECTORS - Abstract
Objective: To assess the diagnostic value of spectral parameters in differentiating adrenal adenomas from metastases based on dual-layer detector spectral CT (DLSCT). Materials and methods: Patients with adenomas or metastases who underwent enhanced DLSCT of the adrenals were enrolled. The CT values of virtual non-contrast images (CT
VNC ), iodine density (ID) values, and Z-effective (Z-eff) values, the normalized iodine density (NID) values, slopes of spectral HU curves (s-SHC), and iodine-to-CTVNC ratios of the tumors were measured in each phase. Receiver operating characteristic (ROC) curves were used to compare the diagnostic values. Results: Ninety-nine patients with 106 adrenal lesions (63 adenomas, 43 metastases) were included. In the venous phase, all spectral parameters were significantly different between adenomas and metastases (all p < 0.05). The combined spectral parameters showed a better diagnostic performance in the venous phase than in other phase (p < 0.05). The iodine-to-CTVNC value had a larger area under the ROC curve (AUC) than the other spectral parameters in the differential diagnosis of adenomas and metastases, with a diagnostic sensitivity and specificity of 74.4% and 91.9%, respectively. In the differential diagnosis of lipid-rich adenomas, lipid-poor adenomas and metastases, the CTVNC value and s-SHC value also had a larger AUC than the other spectral parameters, with a diagnostic sensitivity of 97.7%, 79.1% and specificity of 91.2%, 93.1%, respectively. Conclusion: On DLSCT, the combined spectral parameters in the venous phase could help better distinguish adrenal adenomas from metastases. The iodine-to-CTVNC , CTVNC and s-SHC values had the highest AUC values in differentiating adenomas, lipid-rich adenomas and lipid-poor adenomas from metastases, respectively. [ABSTRACT FROM AUTHOR]- Published
- 2023
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8. Significance of spread through air spaces in small cell lung cancer.
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Han, Lu, Huang, Zhida, Zhang, Jing, Chen, Yan, Wang, Jue, Xiong, Yicheng, Yao, Wangchao, Hou, Likun, Zhang, Liping, Yu, Huansha, Song, Nan, Zhang, Zhonghong, and Zhu, Yuming
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SMALL cell lung cancer ,METASTASIS - Abstract
Purpose: Tumor spread through air space (STAS) is a novel pattern of invasion related to poor prognosis in non-small cell cancer (NSCLC). Nevertheless, little is known about the role of STAS in small cell lung cancer (SCLC). We sought to determine whether STAS has a significant effect on recurrence among SCLC patients. Methods: We collected clinical and follow-up information from 181 resected stage I–III SCLC patients and compared overall survival (OS) and disease-free survival (DFS) between the patients with or without STAS using the Kaplan‒Meier method. To explore the effect of STAS on recurrence, a competing-risk analysis was conducted. Results: Among 181 SCLC patients, STAS was observed in 56 (30.94%) patients, and 125 (69.06%) patients did not have STAS. Furthermore, 33 (18.23%) patients had recurrence, including 12 patients with brain metastases. Patients with STAS had worse DFS. The cumulative incidence of any recurrence was higher in patients with STAS than in those without STAS. Univariate and multivariate competing-risk regression analyses revealed that sublobar resection and STAS were independent risk factors for SCLC recurrence (p = 0.009 and p = 0.029 for multivariate analysis, respectively). Conclusion: SCLC patients with STAS have worse DFS than SCLC patients without STAS. STAS is an independent prognostic factor in SCLC patients. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Perianal superficial CD34-positive fibroblastic tumor: A case report
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Chen-Yan Long and Tao-Li Wang
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Fibroblastic Tumor ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Perianal Abscess ,CD34 ,Histology ,Physical examination ,General Medicine ,Superficiality ,medicine.disease ,Metastasis ,Perianal ,CD34-positive ,Fibroblast tumor ,Diagnosis ,Case report ,medicine ,Immunohistochemistry ,Radiology ,business ,Myofibroblast - Abstract
Background Superficial CD34-positive fibroblast tumors (SCPFTs) are newly recognized fibroblast and myofibroblast tumors representing intermediate tumors. To the best of our knowledge, fewer than 50 cases have been reported. Perianal SCPFT has not been previously reported. Case summary A 55-year-old man was hospitalized upon discovering a painless perianal lump 10 d prior. Physical examination showed a lump of approximately 3 cm × 4 cm in the 7 to 8 o'clock direction in the perianal area. Perianal abscess was considered the primary diagnosis. Lump removal surgery was performed under epidural anesthesia. Postoperative pathology showed a well-circumscribed, soft tissue-derived, spindle-cell tumor with strong CD34 positivity by immunohistochemistry. The final diagnosis was perianal SCPFT. There were no complications, and the patient was followed for more than 8 mo without recurrence or metastasis. Conclusion We report a case of perianal superficial CD34-positive fibroblast tumor. This rare mesenchymal neoplasm has distinctive histomorphology, which is important for diagnosis. Comprehensive consideration of clinical information, imaging, histology, and immunohistochemistry is important for diagnosis.
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- 2021
10. IBSP, a potential recurrence biomarker, promotes the progression of colorectal cancer via Fyn/β‐catenin signaling pathway
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Qinsheng Sun, Ying Qin, Yaoyao Zhou, Mengmeng Dai, Lulu Li, Yong Ni, Yuyang Jiang, Chen Yan, Cheng Qiu, and Liping Liu
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Male ,0301 basic medicine ,Cancer Research ,Colorectal cancer ,Apoptosis ,Proto-Oncogene Proteins c-fyn ,medicine.disease_cause ,Metastasis ,0302 clinical medicine ,Databases, Genetic ,Medicine ,diagnosis and treatment ,Biomarker discovery ,beta Catenin ,RC254-282 ,Original Research ,Cancer Biology ,Fyn/β‐catenin signaling pathway ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Middle Aged ,Oncology ,030220 oncology & carcinogenesis ,Disease Progression ,Biomarker (medicine) ,Female ,Signal transduction ,Colorectal Neoplasms ,integrin‐binding sialoprotein (IBSP) ,Colon ,Down-Regulation ,colorectal cancer ,03 medical and health sciences ,FYN ,Biomarkers, Tumor ,Humans ,Integrin-Binding Sialoprotein ,Radiology, Nuclear Medicine and imaging ,RNA, Messenger ,neoplasms ,Cell Proliferation ,business.industry ,Cancer ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Cancer research ,RNA ,Neoplasm Recurrence, Local ,business ,Carcinogenesis ,metastatic recurrence - Abstract
Colorectal cancer (CRC) is a frequently occurring digestive system cancer and postoperative tumor metastasis and recurrence are the main reasons for the failure of CRC treatment. The aim of this study was to identifying and validating key genes associated with metastatic recurrence of CRC. RNA expression of three datasets (GSE17538, GSE32323, and GSE29623) was used for biomarker discovery. We identified integrin‐binding sialoprotein (IBSP) as a candidate biomarker which was validated in three clinical cohorts (GSE41258, GSE21510, and GSE39582) and our clinical specimens. The results suggested that IBSP expression significantly increased at mRNA and protein levels among CRC cases, which was associated with metastatic recurrence, metastasis, high risk of recurrence, and poor survival in CRC. Consistent results were obtained in CRC cells. The relative level of serum IBSP evidently increased among CRC patients relative to normal controls, and downregulated after operation. As suggested by gene set enrichment analysis (GSEA), the IBSP level was associated with cell‐matrix adhesion in CRC. Functional experiments in vitro showed that IBSP promoted the growth and aggressiveness of CRC, and the potential mechanism by which IBSP promoted carcinogenesis of CRC was the abnormal activation of Fyn/β‐catenin signaling pathway. To sum up, findings in the present work indicate that IBSP can serve as the candidate biomarker for the diagnosis, treatment, and prognosis of CRC., In this study, we identified and validated IBSP as a key gene associated with metastatic recurrence of CRC which might serve as the candidate biomarker for the diagnosis, treatment, and prognosis of CRC. Our results suggested that IBSP expression significantly increased at mRNA and protein levels among CRC cases, which was associated with metastatic recurrence, metastasis, high risk of recurrence, and poor survival in CRC. Functional experiments in vitro showed that IBSP promoted the growth and aggressiveness of CRC, and the potential mechanism by which IBSP promoted carcinogenesis of CRC was the abnormal activation of Fyn/β‐catenin signaling pathway.
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- 2021
11. PDCD6 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis through the AKT/GSK3β/β-catenin Pathway.
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WEN, Shi Yuan, LIU, Yan Tong, WEI, Bing Yan, MA, Jie Qiong, and CHEN, Yan Yan
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HEPATOCELLULAR carcinoma ,CELL proliferation ,CELL migration ,CATENINS ,CARCINOGENS ,APOPTOSIS ,INHIBITION of cellular proliferation ,WNT signal transduction - Abstract
Programmed cell death 6 (PDCD6), a Ca
2+ -binding protein, has been reported to be aberrantly expressed in all kinds of tumors. The aim of this study was to explore the role and mechanism of PDCD6 in hepatocellular carcinomas (HCCs). The expression levels of PDCD6 in liver cancer patients and HCC cell lines were analyzed using bioinformatics and Western blotting. Cell viability and metastasis were determined by methylthiazol tetrazolium (MTT) and transwell assays, respectively. And Western blotting was used to test related biomarkers and molecular pathway factors in HCC cell lines. LY294002, a PI3K inhibitor inhibiting AKT, was used to suppress the AKT/GSK3β/β-catenin pathway to help evaluate the role of this pathway in the HCC carcinogenesis associated with PDCD6. The analysis of The Cancer Genome Atlas Database suggested that high PDCD6 expression levels were relevant to liver cancer progression. This was consistent with our finding of higher levels of PDCD6 expression in HCC cell lines than in normal hepatocyte cell lines. The results of MTT, transwell migration, and Western blotting assays revealed that overexpression of PDCD6 positively regulated HCC cell proliferation, migration, and invasion. Conversely, the upregulation of PDCD6 expression in the presence of an AKT inhibitor inhibited HCC cell proliferation, migration, and invasion. In addition, PDCD6 promoted HCC cell migration and invasion by epithelial-mesenchymal transition. The mechanistic investigation proved that PDCD6 acted as a tumor promoter in HCC through the AKT/GSK3β/β-catenin pathway, increasing the expression of transcription factors and cellular proliferation and metastasis. PDCD6 has a tumor stimulative role in HCC mediated by AKT/GSK3β/β-catenin signaling and might be a potential target for HCC progression. [ABSTRACT FROM AUTHOR]- Published
- 2023
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12. Inhibitory Effect of Astragalus Polysaccharide on Premetastatic Niche of Lung Cancer through the S1PR1-STAT3 Signaling Pathway.
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Shen, Ming, Wang, Yan-jun, Liu, Zhao-hua, Chen, Yan-wen, Liang, Qian-kun, Li, Yang, and Ming, Hai-xia
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POLYSACCHARIDES ,BIOLOGICAL models ,HERBAL medicine ,MEDICINAL plants ,ANIMAL experimentation ,LUNG tumors ,METASTASIS ,DISEASES ,CELLULAR signal transduction ,GENE expression ,MYELOID-derived suppressor cells ,DESCRIPTIVE statistics ,ASTRAGALUS (Plants) ,DATA analysis software ,CHINESE medicine - Abstract
As a common malignant tumor, the morbidity and mortality of lung cancer have been rising in recent years. The concept of "premetastatic niche" may lead to a revolutionary change in antitumor metastasis therapeutic strategies. Traditional Chinese medicine with multitargets and lower poisonous agents may be a potentially effective means to intervene in the "premetastatic niche (PMN)" to prevent and treat tumor metastasis. Astragalus polysaccharide (APS) is a substance with strong immune activity in Astragalus membranaceus that has excellent biological activities such as immunomodulation, anti-inflammatory, and antitumor. In this study, we constructed a tumor lung metastasis animal model to explore the intervention mechanism of APS on the premetastatic niche. We found that APS inhibited the formation of the lung premetastatic niche and inhibited the recruitment of myeloid-derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and gene expression of S1PR1, STAT3, and p-STAT3 in the S1PR1/STAT3 signaling pathway were suppressed by APS. In line with the above findings, our results confirmed that APS may inhibit the accumulation of MDSCs in the premetastatic niche through the intervention of the S1PR1-STAT3 signaling pathway to achieve the antitumor effect. [ABSTRACT FROM AUTHOR]
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- 2023
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13. miR-506-loaded gelatin nanospheres target PENK and inactivate the ERK/Fos signaling pathway to suppress triple-negative breast cancer aggressiveness
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Jie Liu, Wei-Hong Guo, Ge Zhang, Shi-Long Zhang, Jing-Bao Li, Wen-Jing Liu, Qiang Chen, Da-Chuan Yin, Chang-Qing Yang, Chen-Yan Zhang, Xin-Li Liu, and Gang Zhao
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0301 basic medicine ,MAPK/ERK pathway ,Cancer Research ,Triple Negative Breast Neoplasms ,Biology ,Metastasis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Breast cancer ,In vivo ,Cell Line, Tumor ,microRNA ,medicine ,Animals ,Humans ,Viability assay ,Protein Precursors ,Extracellular Signal-Regulated MAP Kinases ,Molecular Biology ,Triple-negative breast cancer ,Gene Transfer Techniques ,Enkephalins ,medicine.disease ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,Disease Models, Animal ,MicroRNAs ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Disease Progression ,Gelatin ,Female ,Signal transduction ,Proto-Oncogene Proteins c-fos ,Nanospheres ,Signal Transduction - Abstract
Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Some microRNAs (miRNAs) were abnormally expressed in TNBC, and they are closely related to the occurrence and progression of TNBC. Here, we found that miR-506 was significantly downregulated in TNBC and relatively lower miR-506 expression predicted a poorer prognosis. Moreover, we found that miR-506 could inhibit MDA-MB-231 cell viability, colony formation, migration, and invasion, and suppress the ERK/Fos oncogenic signaling pathway through upregulating its direct target protein proenkephalin (PENK). Therefore, miR-506 was proposed as a nucleic acid drug for TNBC therapy. However, miRNA is unstable in vivo, which limiting its application as a therapeutic drug via conventional oral or injected therapies. Here, a gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA. Exogenous miR-506 mimic was loaded on GNs and injected into the in situ TNBC animal model, and the miR-506 could achieve sustained and controlled release. The results confirmed that overexpression of miR-506 and PENK in vivo through loading on GNs inhibited in situ triple-negative breast tumor growth and metastasis significantly in the xenograft model. Moreover, we indicated that the ERK/Fos signaling pathway was intensively inactivated after overexpression of miR-506 and PENK both in vitro and in vivo, which was further validated by the ERK1/2-specific inhibitor SCH772984. In conclusion, this study demonstrates that miR-506-loaded GNs have great potential in anti-TNBC aggressiveness therapy.
- Published
- 2021
14. Scutellaria Flavonoids Effectively Inhibit the Malignant Phenotypes of Non-small Cell Lung Cancer in an Id1-dependent Manner
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Qiuping Li, Jing Sun, Jian Qiu, Zhengxiao Zhao, Chen Yan, Weiyi Gong, Wenjuan Ma, Shan Jiang, Mihui Li, Nabijan Mohammadtursun, Baojun Liu, Linwei Lu, Jingcheng Dong, and Lumei Liu
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Inhibitor of Differentiation Protein 1 ,Male ,Lung Neoplasms ,alpha7 Nicotinic Acetylcholine Receptor ,Angiogenesis ,non-small cell lung cancer (NSCLC) ,Applied Microbiology and Biotechnology ,Shelterin Complex ,Metastasis ,Mice ,chemistry.chemical_compound ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,alpha 7 nicotinic acetylcholine receptor (α7nAChR) ,Neoplasm Metastasis ,Phosphorylation ,inhibitor of differentiation 1 (Id1) ,Mice, Inbred BALB C ,0303 health sciences ,biology ,Phenotype ,Flavanones ,Guanosine Triphosphate ,Research Paper ,Cell Survival ,Scutellaria ,Telomere-Binding Proteins ,Mice, Nude ,Antineoplastic Agents ,03 medical and health sciences ,Wogonin ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Molecular Biology ,Protein kinase B ,Ecology, Evolution, Behavior and Systematics ,Cell Proliferation ,030304 developmental biology ,Flavonoids ,Plant Extracts ,Cell Biology ,medicine.disease ,biology.organism_classification ,respiratory tract diseases ,Baicalein ,scutellaria flavonoids (SFs) ,chemistry ,A549 Cells ,Cancer research ,Baicalin ,Developmental Biology - Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the world. Inhibitor of differentiation 1 (Id1) is overexpressed in NSCLC and involved in promoting its progression and metastasis. Identifying natural compounds targeting Id1 may have utility in NSCLC treatment. Here, we sought to determine whether the anti-tumor activities of Scutellaria flavonoids (SFs) were related to Id1. We reported that three SFs (baicalin, baicalein and wogonin) exhibited strong antitumor activity in NSCLC cells in vitro and in vivo. Id1 played a pivotal role on blockage of migration and invasion by SFs. Abrogation of invasion and migration mediated by baicalin, baicalein and wogonin were totally abolished by ectopic overexpression of Id1. Mechanistically, baicalin, baicalein and wogonin activated Rap1-GTP binding and dephosphorylated Akt and Src by suppressing a7nAChR, consequently triggering inhibition of Id1. Then attenuation of its downstream mediators, VEGF-A, N-cadherin, vimentin, combined with augment of E-cadherin led to the blockage of proliferation, EMT and angiogenesis of NSCLC. Overall, our data shed light on heretofore-undescribed role of SFs as modulators of Id1, which may be a useful strategy in the treatment of NSCLC.
- Published
- 2019
15. Deubiquitinating enzyme USP9X regulates metastasis and chemoresistance in triple‐negative breast cancer by stabilizing Snail1.
- Author
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Guan, Tangming, Yang, Xiao, Liang, Hui, Chen, Jiayi, Chen, Yan, Zhu, Yingjie, and Liu, Tongzheng
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TRIPLE-negative breast cancer ,CISPLATIN ,DEUBIQUITINATING enzymes ,PACLITAXEL ,METASTATIC breast cancer ,DRUG resistance in cancer cells ,METASTASIS - Abstract
Breast cancer is one of the most common malignancies in women worldwide. Triple‐negative breast cancer (TNBC) is a highly aggressive and metastatic subtype that has the characteristics of easy recurrence, poor prognosis as well as lack of targeted therapeutics. Snail1, a key factor regulating epithelial–mesenchymal transition (EMT) process, contributing to metastasis and chemoresistance in human cancers. However, the molecular mechanism of Snail1 stabilization in cancers is not fully understood. Here, we demonstrate that the deubiquitinating enzyme USP9X deubiquitinates and stabilizes Snail1, thereby promoting metastasis and chemoresistance. The depletion and pharmacological inhibition of USP9X by WP1130, an inhibitor of USP9X, downregulate endogenous Snail1 protein, inhibit cell migration, invasion, metastasis, and increase cellular sensitivity to cisplatin and paclitaxel both in vitro and in vivo, whereas the reconstitution of Snail1 in cells with USP9X depletion at least partially reverses these phenotypes. Overall, our study establishes the USP9X‐Snail1 axis as an important regulatory mechanism of breast cancer metastasis and chemoresistance and provides a rationale for potential therapeutic interventions in the treatment of TNBC. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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16. Progress of non-coding RNAs in triple-negative breast cancer
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Ge Zhang, Da-Chuan Yin, Jie Liu, Zhao Shiqi, Li-Heng Luo, Xin-Li Liu, Chen-Yan Zhang, Gang Zhao, and Shi-Long Zhang
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0301 basic medicine ,RNA, Untranslated ,Cell ,Triple Negative Breast Neoplasms ,Biology ,030226 pharmacology & pharmacy ,General Biochemistry, Genetics and Molecular Biology ,Chromatin remodeling ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,microRNA ,medicine ,Biomarkers, Tumor ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Triple-negative breast cancer ,General Medicine ,RNA, Circular ,Cell cycle ,medicine.disease ,Non-coding RNA ,Prognosis ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Cancer research ,Female ,RNA, Long Noncoding ,Transcriptome - Abstract
Non-coding RNAs (ncRNAs) include miRNA, lncRNA, and circRNA. NcRNAs are involved in multiple biological processes, including chromatin remodeling, signal transduction, post-transcriptional modification, cell autophagy, carbohydrate metabolism, and cell cycle regulation. Triple negative breast cancer (TNBC) is notorious for high invasiveness and metastasis, poor prognosis, and high mortality, and it is the most malignant breast cancer, while the effective targets for TNBC treatment are still lacking. NcRNAs act as oncogenes or suppressor genes, as well as promote or inhibit the occurrence and development of TNBC. Here, we reviewed some important miRNAs, lncRNAs, circRNAs, their target(s) and molecular mechanisms in TNBC. It is benefited to understand the occurrence and development of TNBC, further some ncRNAs might be potential targets for TNBC treatment.
- Published
- 2020
17. Icaritin ameliorates extracellular microparticles‐induced inflammatory pre‐metastatic niche via modulating the cGAS‐STING signaling.
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Tu, Shumei, Mao, Dengxuan, Shi, Mengxin, Zhang, Huangqin, Liu, Congyan, Li, Xiaoqi, Zhao, Yang, Chen, Yan, and Liu, Yuping
- Abstract
The concept of the inflammatory pre‐metastatic niche (PMN) provides a new and promising direction for the prevention and treatment of metastasis. The excessive activation of the GAS‐STING signaling leads to augmented metastasis by promoting the formation of the inflammatory PMN. In this study, tumor‐derived microparticles (MP) were used to establish the PMN model both in vitro and in vivo, and pro‐inflammatory mediators were also employed to evaluate the effects of Icaritin (ICT). It was demonstrated that ICT could inhibit the pulmonary metastasis of B16BL6 melanoma cells in mice via interfering with PMN. The phosphorylation and dimerization of STING and its downstream signaling TBK1‐IFNβ were proved to be diminished in the presence of ICT. Furthermore, we revealed that ICT suppressed the generation of pro‐inflammatory PMN through conferring the inactivation of the STING signaling pathway. CETSA and DARTS assay also confirmed that STING tended to be a target for the action of ICT. Collectively, our findings highlight a new binding mechanism between STING and ICT for the inhibition of transduction of the STING signaling pathway, suggesting that pharmacological or therapeutic intervention of the STING‐TBK1‐IFNβ singling axis may serve as an effective strategy to prevent the progression of inflammatory PMN and lung metastasis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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18. Synergistic strategy with hyperthermia therapy based immunotherapy and engineered exosomes−liposomes targeted chemotherapy prevents tumor recurrence and metastasis in advanced breast cancer.
- Author
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Huang, Haiqin, Shao, Lanlan, Chen, Yan, Tang, Lan, Liu, Tianqing, Li, Junxu, and Zhu, Hongyan
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METASTATIC breast cancer ,LIPOSOMES ,CANCER relapse ,METASTASIS ,DISEASE relapse ,THERMOTHERAPY ,EXOSOMES - Abstract
Advanced breast cancer with recurrent and distal organ metastasis is aggressive and incurable. The current existing treatment strategies for advanced breast cancer are difficult to achieve synergistic treatment of recurrent tumors and distant metastasis, resulting in poor clinical outcomes. Herein, a synergistic therapy strategy composed of biomimetic tumor‐derived exosomes (TEX)‐Liposome‐paclitaxel (PTX) with lung homing properties and gold nanorods (GNR)‐PEG, was designed, respectively. GNR‐PEG, with well biocompatibility, cured recurrent tumors effectively by thermal ablation under the in situ NIR irradiation. Meanwhile, GNR‐mediated thermal ablation activated the adaptive antitumor immune response, significantly increased the level of CD8+ T cells in lungs and the concentration of serum cytokines (tumor necrosis factor‐α, interlekin‐6, and interferon‐γ). Subsequently, TEX‐Liposome‐PTX preferentially accumulated in lung tissues due to autologous tumor‐derived TEX with inherent specific affinity to lung, resulting in a better therapeutic effect on lung metastasis tumors with the assistance of adaptive immunotherapy triggered by GNR in vivo. The enhanced therapeutic efficacy in advanced breast cancer was a combination of thermal ablation, adaptive antitumor immunotherapy, and targeted PTX chemotherapy. Hence, the synergistic strategy based on GNR and TEX‐Liposome provides selectivity to clinical treatment of advanced breast cancer with recurrent and metastasis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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19. USP5 promotes breast cancer cell proliferation and metastasis by stabilizing HIF2α.
- Author
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Huang, Weixiao, Liu, Xiong, Zhang, Yao, Deng, Mingxia, Li, Guangqiang, Chen, Guo, Yu, Li, Jin, Lai, Liu, Tongzheng, Wang, Yijie, and Chen, Yan
- Subjects
CANCER cells ,CANCER cell proliferation ,BREAST cancer ,DEUBIQUITINATING enzymes ,HYPOXIA-inducible factors ,PROTEIN stability - Abstract
Hypoxia‐inducible factor 2α (HIF2α) plays a pivotal role in breast tumor growth and metastasis. However, the regulatory mechanisms of HIF2α protein stability remain poorly understood. The precise role of the deubiquitinase (DUB) ubiquitin‐specific peptidase 5 (USP5) in breast cancer and the underlying mechanism remains largely unknown. Here, we identified USP5 as a novel DUB for HIF2α. Physically, USP5 interacts with HIF2α and protects HIF2α from ubiquitin‐proteasome degradation, thereby promoting the transcription of HIF2α target genes, such as SLC2A1, PLOD2, P4HA1, and VEGFA. USP5 ablation impairs breast cancer cells proliferation, colony formation, migration, and invasion. Moreover, USP5 is highly expressed in breast cancer, and the protein levels of USP5 are positively correlated with HIF2α protein levels in human breast cancer tissues. Importantly, high levels of USP5 leads to poor clinical outcome in patients with breast cancer. Collectively, USP5 stabilizes HIF2α through its DUB activity and provides a potential therapeutic target for breast cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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20. A Zic2/Runx2/NOLC1 signaling axis mediates tumor growth and metastasis in clear cell renal cell carcinoma
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Shi Lu Chen, Xia Yang, Yun Cao, Lei Li, Chris Zhiyi Zhang, and Chen-Yan Wu
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0301 basic medicine ,Cancer Research ,Immunology ,Mice, Nude ,Core Binding Factor Alpha 1 Subunit ,Biology ,Transfection ,Article ,Metastasis ,Tumour biomarkers ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,Renal cell carcinoma ,Cell Line, Tumor ,medicine ,Animals ,Humans ,lcsh:QH573-671 ,Neoplasm Metastasis ,Transcription factor ,Carcinoma, Renal Cell ,Cell Proliferation ,Cell growth ,lcsh:Cytology ,Cell Biology ,medicine.disease ,Prognosis ,Kidney Neoplasms ,Up-Regulation ,Blot ,Gene Expression Regulation, Neoplastic ,Clear cell renal cell carcinoma ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Immunohistochemistry ,Signal Transduction - Abstract
Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies with rapid growth and high metastasis, but lacks effective therapeutic targets. Here, using public sequencing data analyses, quantitative real-time PCR assay, western blotting, and IHC staining, we characterized that runt-related transcription factor 2 (Runx2) was significantly upregulated in ccRCC tissues than that in normal renal tissues, which was associated with the worse survival of ccRCC patients. Overexpression of Runx2 promoted malignant proliferation and migration of ccRCC cells, and inversely, interfering Runx2 with siRNA attenuates its oncogenic ability. RNA sequencing and functional studies revealed that Runx2 enhanced ccRCC cell growth and metastasis via downregulation of tumor suppressor nucleolar and coiled-body phosphoprotein 1 (NOLC1). Moreover, increased Zic family member 2 (Zic2) was responsible for the upregulation of Runx2 and its oncogenic functions in ccRCC. Kaplan–Meier survival analyses indicated that ccRCC patients with high Zic2/Runx2 and low NOLC1 had the worst outcome. Therefore, our study demonstrates that Zic2/Runx2/NOLC1 signaling axis promotes ccRCC progression, providing a set of potential targets and prognostic indicators for patients with ccRCC.
- Published
- 2020
21. Nicaraven reduces cancer metastasis to irradiated lungs by decreasing CCL8 and macrophage recruitment
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Lan Luo, Chen Yan, Shinji Goto, Tao-Sheng Li, and Yoshishige Urata
- Subjects
0301 basic medicine ,Niacinamide ,Cancer Research ,Lung Neoplasms ,Radioprotective Agent ,Macrophage ,medicine.medical_treatment ,Radiation-Protective Agents ,CCL8 ,Radiation Tolerance ,Antioxidants ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Amifostine ,Cell Line, Tumor ,medicine ,Animals ,Chemokine CCL8 ,Humans ,Radiosensitivity ,Lung ,Nicaraven ,Radiation ,business.industry ,Macrophages ,Cancer ,Lewis lung carcinoma ,respiratory system ,medicine.disease ,respiratory tract diseases ,Radiation therapy ,Mice, Inbred C57BL ,030104 developmental biology ,Oncology ,Gamma Rays ,030220 oncology & carcinogenesis ,Cancer research ,business ,medicine.drug - Abstract
Radiotherapy for cancer patients damages normal tissues, thereby inducing an inflammatory response and promoting cancer metastasis. We investigated whether nicaraven, a compound with radioprotective and anti-inflammatory properties, could attenuate radiation-induced cancer metastasis to the lungs of mice. Nicaraven and amifostine, another commercial radioprotective agent, had limited effects on both the radiosensitivity of Lewis lung carcinoma cells in vitro and radiation-induced tumor growth inhibition in vivo. Using experimental and spontaneous metastasis models, we confirmed that thorax irradiation with 5 Gy X-rays dramatically increased the number of tumors in the lungs. Interestingly, the number of tumors in the lungs was significantly reduced by administering nicaraven but not by administering amifostine daily after radiation exposure. Furthermore, nicaraven administration effectively inhibited CCL8 expression and macrophage recruitment in the lungs 1 day after thorax irradiation. Our data suggest that nicaraven attenuates radiation-induced lung metastasis, likely by regulating the inflammatory response after radiation exposure., Cancer Letters, 418, pp.204-210; 2018
- Published
- 2018
22. RNA binding motif protein 3: a potential biomarker in cancer and therapeutic target in neuroprotection
- Author
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Ren-Bin Zhou, Xiao-Li Lu, Da-Chuan Yin, and Chen-Yan Zhang
- Subjects
0301 basic medicine ,RNA-binding protein ,Antineoplastic Agents ,Review ,Biology ,Bioinformatics ,Neuroprotection ,RNA binding protein 3 ,Proto-Oncogene Mas ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,medicine ,Protein biosynthesis ,cancer ,Humans ,Messenger RNA ,Cancer ,RNA-Binding Proteins ,medicine.disease ,Biomarker (cell) ,030104 developmental biology ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer research ,biomarker ,neuroprotection ,Biomarkers - Abstract
// Ren-Bin Zhou 1 , Xiao-Li Lu 1 , Chen-Yan Zhang 1 and Da-Chuan Yin 1 1 Key Laboratory for Space Bioscience & Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, Shaanxi, PR China Correspondence to: Da-Chuan Yin, email: // Keywords : RNA binding protein 3, cancer, biomarker, neuroprotection Received : September 24, 2016 Accepted : January 10, 2017 Published : January 19, 2017 Abstract RNA binding motif 3 (RBM3) is a highly conserved cold-induced RNA binding protein that is transcriptionally up-regulated in response to harsh stresses. Featured as RNA binding protein, RBM3 is involved in mRNA biogenesis as well as stimulating protein synthesis, promoting proliferation and exerting anti-apoptotic functions. Nowadays, accumulating immunohistochemically studies have suggested RBM3 function as a proto-oncogene that is associated with tumor progression and metastasis in various cancers. Moreover, emerging evidences have also indicated that RBM3 is equally effective in neuroprotection. In the present review, we provide an overview of current knowledge concerning the role of RBM3 in various cancers and neuroprotection. Additionally, its potential roles as a promising diagnostic marker for cancer and a possible therapeutic target for neuro-related diseases are discussed.
- Published
- 2017
23. Bcl2-associated athanogene 4 promotes the invasion and metastasis of gastric cancer cells by activating the PI3K/AKT/NF-κB/ZEB1 axis.
- Author
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Jiang, Lei, Chen, Yan, Min, Guangtao, Wang, Jun, Chen, Wei, Wang, Hongpeng, Wang, Xiangwen, and Yao, Nan
- Subjects
- *
STOMACH cancer , *METASTASIS , *LYMPHATIC metastasis , *CANCER cells , *EPITHELIAL-mesenchymal transition , *STOMACH tumors , *PROTEINS , *RESEARCH , *PHOSPHOTRANSFERASES , *CANCER invasiveness , *CELL physiology , *NF-kappa B , *EVALUATION research , *CELL motility , *CELLULAR signal transduction , *COMPARATIVE studies , *GENES , *CELL lines , *CARRIER proteins , *CHEMICAL inhibitors - Abstract
Bcl2-associated athanogene 4 (BAG4) has been found to be aberrantly expressed in several types of human cancers. However, little is known about its expression, role, and clinical significance in gastric cancer (GC). In this study, we aimed to address these issues and to explore the underlying mechanisms. The expression level of BAG4, measured by immunohistochemistry, was significantly higher in GC tissues than in paired normal tissues. Elevated BAG4 expression was positively correlated with T stage, lymph node metastasis, and tumor size of GC and was associated with unfavorable outcomes of the patients. The overexpression of BAG4 promoted the in vitro invasion and in vivo metastasis of GC cells, and opposite results were observed after silencing of BAG4. Silencing of BAG4 significantly reduced the phosphorylation of PI3K, AKT, and p65, whereas overexpression of BAG4 markedly enhanced the phosphorylation of these molecules. At the same time, manipulating BAG4 expression resulted in the corresponding changes in p65 nuclear translocation and ZEB1 expression. Luciferase reporter and chromatin immunoprecipitation assays verified that p65 binds to the promoter of ZEB1 to upregulate its transcription. Our results demonstrate that BAG4 plays an oncogenic role in the invasion and metastasis of GC cells by activating the PI3K/AKT/NF-κB/ZEB1 axis to induce epithelial-mesenchymal transition. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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24. Targeted Lipid Nanoparticles Encapsulating Dihydroartemisinin and Chloroquine Phosphate for Suppressing the Proliferation and Liver Metastasis of Colorectal Cancer.
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Peng, Jianqing, Wang, Qin, Zhou, Jia, Zhao, Shuli, Di, Pan, Chen, Yan, Tao, Ling, Du, Qianming, Shen, Xiangchun, and Chen, Yi
- Subjects
COLORECTAL cancer ,LIVER metastasis ,METASTASIS ,ARTEMISININ derivatives ,LABORATORY mice ,IRINOTECAN - Abstract
Antimalarial drugs Dihydroartemisinin (DHA) and chloroquine phosphate (CQ) exhibit evident anti-cancer activity, particularly as combination therapy. DHA and CQ combination therapy has been proved to exhibit higher cytotoxic effect in tumor cells and lower toxicity to normal cells than combination of artemisinin derivatives (ARTs) and anticancer chemotherapy drugs. However, different physiochemical properties of DHA and CQ, leading to distinctive in vivo outcomes, considerably limited their synergistic effect in cancer treatment. Herein, we developed a lipid nanoparticle (LNP) for co-delivery of DHA and CQ to inhibit proliferation and metastasis of colorectal cancer. Considering the beneficial effects of acid/reactive oxide species (ROS)-sensitive phospholipids and targeting ligands for colorectal cancer cells, an RGD peptide-modified pH/ROS dual-sensitive LNP loaded with DHA and CQ (RLNP/DC) was prepared. It exhibited optimal cytotoxicity and suppression of invasion and metastasis in HCT116 cells in vitro , attributable to irreversible upregulation of intracellular ROS levels, downregulation of VEGF expression, and upregulation of paxillin expression. A mouse model of orthotopic metastasis of colorectal cancer was established to evaluate anti-proliferation and anti-metastasis effects of RLNP/DC in vivo. Thus, an optimized nanoplatform for DHA and CQ combination therapy was developed in this study that offered potential antitumor efficacy against colorectal cancer. [ABSTRACT FROM AUTHOR]
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- 2021
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25. Recent treatment progress of triple negative breast cancer
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Lu Hui-Meng, Gong Zi-Qian, Yang Chang-Qing, Zhao Shi-Qi, Zhang Chen-Yan, Zhao Gang, Liu Jie, Yin Dachuan, Zhou Ren-Bin, Xu Ran, and Zhu Kun
- Subjects
Oncology ,medicine.medical_specialty ,Chemotherapy ,Side effect ,business.industry ,medicine.medical_treatment ,Biophysics ,Estrogen receptor ,Triple Negative Breast Neoplasms ,Disease ,medicine.disease ,Prognosis ,Metastasis ,Breast cancer ,Internal medicine ,Progesterone receptor ,medicine ,Humans ,Neoplasm Metastasis ,business ,Molecular Biology ,Triple-negative breast cancer ,Signal Transduction - Abstract
Breast cancer (BC) is a serious worldwide disease that threatens women's health. Particularly, the morbidity of triple-negative breast cancer (TNBC) is higher than that of other BC types due to its high molecular heterogeneity, metastatic potential and poor prognosis. TNBC lacks of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), so there are still no effective treatment methods for TNBC. Here, we reviewed the classification of TNBC, its molecular mechanisms of pathogenesis, treatment methods and prognosis. Finding effective targets is critical for the treatment of TNBC. Also, refining the classification of TNBC is benefited to choose the treatment of TNBC, because the sensitivity of chemotherapy is different in different TNBC. Some new treatment methods have been proposed in recent years, such as nutritional therapy and noncoding RNA treatment methods. There are some disadvantages, such as the side effect on normal cells after nutrient deprivation, low specificity and instability of noncoding RNA. More studies are necessary to improve the treatment of TNBC.
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- 2019
26. Clivus metastasis of hepatocellular carcinoma causing hypopituitarism
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Chen Yan, Lanisha D Fuller, and Richard A. Prayson
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Pathology ,medicine.medical_specialty ,medicine.anatomical_structure ,Clivus ,business.industry ,Hepatocellular carcinoma ,medicine ,Hypopituitarism ,medicine.disease ,business ,Metastasis - Published
- 2020
27. Targeting Glutaminase 1 Attenuates Stemness Properties in Hepatocellular Carcinoma by Increasing Reactive Oxygen Species and Suppressing Wnt/Beta-Catenin Pathway
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Chen Yan, Liyuan Qian, Tiancheng Xu, Decai Yu, Shaohe Wang, Binghua Li, Yitao Ding, Jiwu Wei, Yajuan Cao, Gang Meng, and Ouyang Luo
- Subjects
Big Data ,Male ,0301 basic medicine ,IHC, Immunohistochemistry ,Research paper ,Wnt/β-catenin signaling pathway ,HCC, Hepatocellular carcinoma ,Hepatocellular carcinoma ,Metastasis ,Gene Knockout Techniques ,Mice ,0302 clinical medicine ,Glutaminase 1 ,GEO, Gene Expression Omnibus ,Stemness ,GSH, Glutathione ,α-KG, α-ketoglutarate ,Wnt Signaling Pathway ,medicine.diagnostic_test ,Glutaminase ,Liver Neoplasms ,Wnt signaling pathway ,OXPHOS, Oxidative phosphorylation ,Hep G2 Cells ,General Medicine ,Middle Aged ,Prognosis ,Phenotype ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,IMM, Inner mitochondrial membrane ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,NADPH, Nicotinamide adenine dinucleotide phosphate ,Female ,TCA, Tricarboxylic acid ,GCLC, Glutamate-Cysteine Ligase Catalytic Subunit ,OMM, Outer mitochondrial membrane ,Liver cancer ,Adult ,Carcinoma, Hepatocellular ,TCGA, the Cancer Genome Atlas ,CSC, Cancer stem cell ,Biology ,NAC, N-Acetyl-l-cysteine ,General Biochemistry, Genetics and Molecular Biology ,Flow cytometry ,03 medical and health sciences ,Downregulation and upregulation ,Cancer stem cell ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Aged ,Gln, Glutamine ,medicine.disease ,030104 developmental biology ,Cell culture ,Cancer research ,Glutamine metabolism ,DM-α-KG, Dimethyl 2-oxoglutarate ,CRISPR-Cas Systems ,Reactive Oxygen Species ,GLS1, Glutaminase 1 ,Neoplasm Transplantation ,ROS, Reactive oxygen species - Abstract
Background: Hepatocellular carcinoma (HCC) is an aggressive malignant disease with poor prognosis. Recent advances suggest the existence of cancer stem cells (CSCs) within liver cancer, which are considered to be responsible for tumor relapse, metastasis, and chemoresistance. However, novel therapeutic approaches for eradication of CSCs are yet to be established. Here, we aimed to identify the role of glutaminase 1 (GLS1) in stemness, and the feasibility that GLS1 serves as a therapeutic target for elimination CSCs as well as the possible mechanism. Methods: Publicly-available data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was mined to unearth the association between GLS1 and stemness phenotype. Using big data, human tissues and multiple cell lines, we gained a general picture of GLS1 expression in HCC progression. We generated stable cell lines by lentiviral-mediated overexpression or CRISPR/Cas9-based knockout. Sphere formation assays and colony formation assays were employed to analyze the relationship between GLS1 and stemness. A series of bioinformatics analyses and molecular experiments including qRT-PCR, immunoblotting, flow cytometry and immunofluorescence were employed to investigate the role of GLS1 in regulating stemness in vitro and in vivo. Results: We observed GLS1 (both KGA and GAC isoform) is highly expressed in HCC, and that high expression of GAC predicts a poor prognosis. GLS1 is exclusively expressed in the mitochondrial matrix. Upregulation of GLS1 is positively associated with advanced clinicopathological features and stemness phenotype. Targeting GLS1 reduced the expression of stemness-related genes and suppressed CSC properties in vitro. We further found GLS1 regulates stemness properties via ROS/Wnt/β-catenin signaling and that GLS1 knockout inhibits tumorigenicity in vivo. Conclusions: Targeting GLS1 attenuates stemness properties in HCC by increasing ROS accumulation and suppressing Wnt/β-catenin pathway, which implied that GLS1 could serve as a therapeutic target for elimination of CSCs. Funding: This work was supported by grants from the Nature Science Foundation of China (No. 81871967), Social Development Foundation of Jiangsu Province of China (No. BE2018604), Jiangsu Provincial Medical Talent, the Nanjing Science and Technology Project (No. 201803028) and the Fundamental Research Funds for the Central Universities (YG1805016 021414380375). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: All experimental protocols were approved by the research ethics committee of Drum Tower hospital and research ethics approval for this project was granted from the same institution.
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- 2018
28. The Association of microRNA-34a With High Incidence and Metastasis of Lung Cancer in Gejiu and Xuanwei Yunnan.
- Author
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Chen, Yan, Hou, Chun, Zhao, Liu-xin, Cai, Qiu-chen, Zhang, Ying, Li, Da-lun, Tang, Yao, Liu, Hong-yu, Liu, Yun-yi, Zhang, Yue-yan, Yang, Ya-kun, Gao, Cheng-wei, Yao, Qian, Zhu, Qi-shun, and Cao, Chuan-hai
- Subjects
LUNG cancer ,METASTASIS ,TUMOR suppressor genes ,GENE regulatory networks ,BLADDER cancer ,TUMOR growth - Abstract
The incidence and associated mortality of lung cancer in tin miners in Gejiu County and farmers in Xuanwei Country, Yunnan Province have been very high in the world. Current published literatures on the molecular mechanisms of lung cancer initiation and progression in Gejiu and Xuanwei County are still controversial. Studies confirmed that microRNA-34a (miR-34a) functioned as a vital tumor suppressor in tumorigenesis and progression. However, the role and precise mechanisms of miR-34a and its regulatory gene network in initiation and progression of lung cancer in Gejiu and Xuanwei County, Yunnan Province, have not been elucidated. In the current study, we first found that miR-34a was downregulated in Gejiu lung squamous carcinoma YTMLC-90, Xuanwei lung adenocarcinoma XWLC-05, and other non-small cell lung carcinoma (NSCLC) cell lines, and miR-34a overexpression inhibited cell proliferation, migration and invasion, as well as induced cell apoptosis in YTMLC-90 and XWLC-05 cells. Our findings revealed that miR-34a is critical and cannot be considered as the area-specific non-coding RNA in initiation and progression of lung cancer in Gejiu and Xuanwei County. Next we revealed that miR-34a overexpression suppressed lung cancer growth and metastasis partially via increasing PTEN but reducing CDK6 expression that might lead to subsequent inactivation of PI3K/AKT pathway. Furthermore, our findings demonstrated that YY1 functioned as a tumor suppressor gene in initiation and progression of lung cancer in Gejiu and Xuanwei County. In conclusion, our findings in the study confirmed that miR-34a overexpression could simultaneously suppress tumor growth and metastasis and play a vital role in tumorigenesis and progression of NSCLC via increasing PTEN and YY1 expression, but decreasing CDK6. Most interestingly, our findings also raised doubts about the current ideas about these area-specific diseases. [ABSTRACT FROM AUTHOR]
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- 2021
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29. Penile metastases from primary lung cancer
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Guo, Ling-Chuan, Li, Gang, Wang, Xi-Ming, Zhang, Mi, Huang, Jian-An, and Chen, Yan-Bin
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Male ,Lung Neoplasms ,perineal pain ,Middle Aged ,penile cancer ,lung cancer ,Carcinoma, Adenosquamous ,Fatal Outcome ,case report ,metastasis ,Humans ,Clinical Case Report ,Penile Neoplasms ,Research Article - Abstract
Background: Metastasis to the penis from primary lung cancer is quite rare. To improve the understanding, we present a case diagnosed as penile metastasis from primary lung cancer and review the literature. Methods: One case report and retrospectively analysis penile cancer patient secondary from primary lung cancer. Results: The patient complained of perineal pain and burning on urination for about 2 months. On physical examination, painful nodular masses at the base of left side of the corpora cavernosa were found. 18F-fluorodeoxyglucose positron emission tomography/CT (PET/CT) scan showed that maximum standardized uptake value (SUVmax) in left side corpora cavernosa and right hilar increased to 12.0 and 13.5 respectively. On flexible bronchoscopy checking, stenosis of the opening of apical segmental and posterior segmental bronchi of right upper lobe was found. The lateral segmental bronchi of left lower lobe was obstructed by a neoplasm. The pathological result was primary pulmonary adenosquamous carcinoma (ASC). Two months later, total penectomy was performed. The pathological result was penile ASC derived from pulmonary. On reviewing the literature, there are 39 cases reported. The patient we present is the 40th one. The average age at diagnosis was (60.5 ± 10.7) years old. The most common symptom was mass, followed by priapism, pain. The overall survival time was (4.5 ± 3.9) months. Conclusions: The penis may be a site of metastasis from lung cancer, especially for old patient. Metastasis to the penis usually indicates that the primary lung cancer is at an advanced stage and the prognosis is very poor.
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- 2017
30. Elevated heparanase expression is associated with poor prognosis in breast cancer : a study based on systematic review and TCGA data
- Author
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Shijian Chen, Yi Zhang, Xu Sun, Lin Yang, Jin-Ping Li, Pei-Yu Cheng, Jiayun Nian, Gan-Lin Zhang, Guo-Wang Yang, Hui Meng, Xiaomin Wang, Mingwei Yu, Chen Yan, and Yunfei Ma
- Subjects
0301 basic medicine ,Oncology ,Gerontology ,medicine.medical_specialty ,Poor prognosis ,Breast Neoplasms ,Lymph node metastasis ,Traditional Chinese medicine ,Review ,Metastasis ,heparanase ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,Internal medicine ,medicine ,Biomarkers, Tumor ,Odds Ratio ,Humans ,Heparanase ,Glucuronidase ,Neoplasm Staging ,Cancer och onkologi ,Tumor size ,business.industry ,Odds ratio ,medicine.disease ,Prognosis ,humanities ,Gene Expression Regulation, Neoplastic ,Patient Outcome Assessment ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer and Oncology ,Female ,prognosis ,Neoplasm Grading ,business ,Publication Bias - Abstract
// Xu Sun 1 , Ganlin Zhang 1 , Jiayun Nian 1,2 , Mingwei Yu 1 , Shijian Chen 3 , Yi Zhang 1 , Guowang Yang 1 , Lin Yang 1 , Peiyu Cheng 1 , Chen Yan 1,2 , Yunfei Ma 1 , Hui Meng 1,2 , Xiaomin Wang 1 and Jin-Ping Li 1,4 1 Department of Oncology, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing, China 2 School of Graduates, Beijing University of Chinese Medicine, Beijing, China 3 Department of Neurology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China 4 Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden Correspondence to: Xiaomin Wang, email: // Keywords : heparanase, breast cancer, prognosis Received : September 09, 2016 Accepted : March 10, 2017 Published : March 25, 2017 Abstract Heparanase promotes tumorigenesis, angiogenesis, and metastasis. Here, we conducted a study based on systematic review and the Cancer Genome Atlas (TCGA) data that examined heparanase expression in clinical samples to determine its prognostic value. According to the meta-analysis and TCGA data, we found that heparanase expression was up-regulated in most breast cancer specimens, and elevated heparanase expression was associated with increased lymph node metastasis, larger tumor size, higher histological grade, and poor survival. These results suggest that targeting heparanase might improve treatments for breast cancer patients.
- Published
- 2017
31. Celastrol inhibits ezrin-mediated migration of hepatocellular carcinoma cells.
- Author
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Du, Shihao, Song, Xiaoyu, Li, Yuan, Cao, Yalei, Chu, Fuhao, Durojaye, Olanrewaju Ayodeji, Su, Zeqi, Shi, Xiaoguang, Wang, Jing, Cheng, Juan, Wang, Tangshun, Gao, Xiang, Chen, Yan, Zeng, Wuzhekai, Wang, Fengsong, Wang, DongMei, Liu, Xing, and Ding, Xia
- Subjects
DISEASE progression ,EMIGRATION & immigration ,HEPATOCELLULAR carcinoma ,CANCER cells ,METASTASIS - Abstract
Progression of hepatocellular carcinoma involves multiple genetic and epigenetic alterations that promote cancer invasion and metastasis. Our recent study revealed that hyperphosphorylation of ezrin promotes intrahepatic metastasis in vivo and cell migration in vitro. Celastrol is a natural product from traditional Chinese medicine which has been used in treating liver cancer. However, the mechanism of action underlying celastrol treatment was less clear. Here we show that ROCK2 is a novel target of celastrol and inhibition of ROCK2 suppresses elicited ezrin activation and liver cancer cell migration. Using cell monolayer wound healing, we carried out a phenotype-based screen of natural products and discovered the efficacy of celastrol in inhibiting cell migration. The molecular target of celastrol was identified as ROCK2 using celastrol affinity pull-down assay. Our molecular docking analyses indicated celastrol binds to the active site of ROCK2 kinase. Mechanistically, celastrol inhibits the ROCK2-mediated phosphorylation of ezrin at Thr567 which harnesses liver cancer cell migration. Our findings suggest that targeting ROCK2-ezrin signaling is a potential therapeutic niche for celastrol-based intervention of cancer progression in hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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32. SNCG promotes the progression and metastasis of high-grade serous ovarian cancer via targeting the PI3K/AKT signaling pathway.
- Author
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Zhang, Jing, Liu, Xiao-han, Li, Cong, Wu, Xiao-xing, Chen, Yan-lin, Li, Wen-wen, Li, Xian, Gong, Fan, Tang, Qin, and Jiang, Dan
- Subjects
OVARIAN cancer ,OVARIAN epithelial cancer ,WESTERN immunoblotting ,MULTIPLE regression analysis ,BENIGN tumors ,FALLOPIAN tubes ,METASTASIS - Abstract
Background: The poor prognosis of patients with ovarian cancer is mainly due to cancer progression. γ-Synuclein (SNCG) has reported as a critical player in cancer metastasis. However, its biological roles and mechanism are yet incompletely understood in ovarian cancer, especially in high-grade serous ovarian cancer (HGSOC). Methods: This is a retrospective study of 312 patients with ovarian cancer at a single center between 2006 and 2016. Ovarian cancer tissues were stained by immunohistochemistry to analyze the relationship between SNCG expression and clinicopathologic factors. The clinical outcomes versus SNCG expression level were evaluated by Kaplan–Meier method and multiple Cox regression analysis. Next, systematical functional experiments were given to examine the proliferation and metastatic abilities of SNCG both in vitro and in vivo using loss- and gain- of function approaches. Furthermore, the mechanisms of SNCG overexpression were examined by human phospho-kinase array kit and western blot analysis. Results: Clinically, the expression of SNCG was significantly upregulated in ovarian cancer compared with the borderline and benign tumor, normal ovary, and fallopian tube. Notably, the high level of SNCG correlated with high-risk clinicopathologic features and showed poor survival for patients with HGSOC, indicating an independent prognostic factor for these patients. Functionally, we observed that overexpression of SNCG promoted cell proliferation, tumor formation, migration, and invasion both in vitro and in vivo. Mechanistically, we identified that SNCG promoted cancer cell metastasis through activating the PI3K/AKT signaling pathway. Conclusions: Our results reveal SNCG up-regulation contributes to the poor clinical outcome of patients with HGSOC and highlight the metastasis-promoting function of SNCG via activating the PI3K/Akt signaling pathway in HGSOC. [ABSTRACT FROM AUTHOR]
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- 2020
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33. Circulating Epstein‐Barr virus microRNAs BART7‐3p and BART13‐3p as novel biomarkers in nasopharyngeal carcinoma.
- Author
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Lu, Tianzhu, Guo, Qiaojuan, Lin, Keyu, Chen, Honglin, Chen, Yixin, Xu, Yuanji, Lin, Cheng, Su, Ying, Chen, Yan, Chen, Mengyuan, Zheng, Yuhong, Ye, Yunbin, Lin, Shaojun, Zong, Jingfeng, and Pan, Jianji
- Abstract
Epstein‐Barr virus (EBV) BamHI A rightward transcripts (BART) encoded microRNAs (EBV‐miR‐BARTs) are abnormally highly expressed in nasopharyngeal carcinoma (NPC). This study aims to investigate the diagnostic and prognostic performance of miR‐BART7‐3p and miR‐BART13‐3p. Plasma levels of EBV DNA, miR‐BART7‐3p, and miR‐BART13‐3p were examined by quantitative PCR in 483 treatment‐naïve NPC patients and 243 controls without NPC. The prognostic performance was examined by comparing plasma levels with rates of distant metastasis during follow‐up. The area under the receiver operating characteristic curve for diagnosing NPC was 0.926 for EBV DNA, 0.964 for plasma miR‐BART7‐3p, 0.973 for miR‐BART13‐3p, and 0.997 for all three indices. Among 465 NPC patients without distant metastasis, the above‐median miR‐BART7‐3p and EBV DNA were independent risk for shorter distant metastasis‐free survival (DMFS) (hazard ratio [HR] = 2.94, 95% confidence interval [CI], 1.44‐5.97, P =.003; HR = 2.27, 95% CI, 1.26‐4.10, P =.006) in multivariate Cox regression. Epstein‐Barr virus DNA, miR‐BART7‐3p, and miR‐BART13‐3p after radiotherapy were detectable in 28.6%, 17.6%, and 54.7% of patients, respectively. In multivariate Cox regression, detectable miR‐BART7‐3p and EBV DNA were independent risks for shorter DMFS (HR = 4.13, 95% CI, 1.89‐9.01, P <.001; HR = 2.14, 95% CI, 1.04‐4.42, P =.039). The 4‐year DMFS rate was 92.0% in subjects (n = 156) with neither detectable miR‐BART7‐3p nor EBV DNA, 80.0% in subjects (n = 65) with either detectable miR‐BART7‐3p or EBV DNA, and 52.9% in subjects (n = 24) with both detectable miR‐BART7‐3p and EBV DNA after radiotherapy (P <.001). Circulating levels of miR‐BART7‐3p and miR‐BART13‐3p show excellent diagnostic performance for NPC. The combination of plasma levels of miR‐BART7‐3p and EBV DNA at diagnosis and after radiotherapy could help stratify patients by risk of poor DMFS. [ABSTRACT FROM AUTHOR]
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- 2020
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34. Effects of oral maintenance chemotherapy and predictive value of circulating EBV DNA in metastatic nasopharyngeal carcinoma.
- Author
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Zhou, Han, Lu, Tianzhu, Guo, Qiaojuan, Chen, Yan, Chen, Mengwei, Chen, Yansong, Lin, Yingying, Chen, Chuanben, Ma, Liqin, Xu, Yun, Lin, Shaojun, and Pan, Jianji
- Subjects
CIRCULATING tumor DNA ,CANCER chemotherapy ,DNA ,CARCINOMA ,METASTASIS ,NASOPHARYNX tumors - Abstract
Background/Objectives: Oral maintenance chemotherapy can effectively prolong overall survival (OS) in many types of metastatic cancer, but its role in metastatic nasopharyngeal carcinoma (mNPC) is unclear. In this study, the efficacy of oral maintenance chemotherapy in mNPC and the effectiveness of circulating tumor EBV‐DNA for screening patients were evaluated. Methods: Between June 2016 and December 2017, 141 patients with mNPC who received platinum‐based systemic chemotherapy were included (median follow‐up time, 21 months). Patients were classified into two groups according to the administration of oral maintenance chemotherapy. Plasma samples were collected before, during, and after treatment for the measurement of circulating EBV DNA. Results: The 2‐year OS was higher for patients who received maintenance chemotherapy than for patients without maintenance chemotherapy (78.9% vs 62.7%, P =.016). Patients with undetectable posttreatment EBV‐DNA after 4‐6 cycles of systemic chemotherapy (n = 73) had a higher 2‐year OS than that of patients with detectable EBV‐DNA (n = 68) (82.16% vs 51.45%, P =.001). For patients with undetectable posttreatment EBV‐DNA, OS was better for those with maintenance chemotherapy than for those without (86.7% vs 73%, P =.027). For patients with detectable posttreatment EBV‐DNA, maintenance chemotherapy did not improve outcomes (49.5% vs 55.4%, P =.824). The most common acute events were hematological toxicity, and all were tolerable and curable. Conclusions: Oral maintenance chemotherapy with S1 or capecitabine can improve OS in mNPC. Posttreatment EBV‐DNA was not only an independent prognosis factor for mNPC but also can screen out beneficiaries of maintenance chemotherapy. [ABSTRACT FROM AUTHOR]
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- 2020
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35. Clinical Study on Prelaryngeal Lymph Node Metastasis in Papillary Thyroid Carcinoma.
- Author
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Gong, Jin-Xing, Gu, Jian-Wei, Ji, Feng, Li, Kun, Zhu, Qi, Gu, Fang-Ying, Chen, Yan, and Ji, Qing-Hai
- Subjects
LYMPH nodes ,THYROID cancer ,PAPILLARY carcinoma ,LYMPHADENECTOMY ,NECK dissection ,LARYNGEAL cancer ,METASTASIS ,THYROIDECTOMY - Abstract
aims to investigate the risk factors of prelaryngeal lymph node metastasis in papillary thyroid carcinoma and its clinical application value. Methods: The clinical pathological features and metastatic risks were statistically analyzed by reviewing 254 patients with papillary thyroid carcinoma, who received their first operation and prelaryngeal lymph node dissection in our department. Results: The detection of prelaryngeal lymph nodes, tumor size and any paratracheal lymph node metastasis were correlated with the number of paratracheal lymph node metastasis (P< 0.05), but these were not correlated with age, gender, multiple foci, tumor size, any paratracheal lymph node metastasis, metastatic location, or foci location (P> 0.05). Conclusion: Paratracheal lymph node metastasis indicates a high possibility of prelaryngeal lymph node metastasis. Paratracheal lymph node dissection combined with prelaryngeal lymph node dissection should be simultaneously considered in operations for thyroid papilla carcinoma. [ABSTRACT FROM AUTHOR]
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- 2020
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36. Primitive Neuroectodermal Tumor of the Prostate with Notalgia and Paraplegia as the Initial Symptoms: A Case Report and Literature Review.
- Author
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Du, Tian-Qi, Li, Xiang, Diao, Huan-Rong, Chen, Yan-Zhi, Yan, Ying, and Zhao, Yu-Xia
- Subjects
PROSTATE tumors treatment ,COMPUTED tomography ,METASTASIS ,NEEDLE biopsy ,PARAPLEGIA ,PROSTATE ,PROSTATE tumors ,SURVIVAL ,POSITRON emission tomography ,SENSORY disorders ,DISEASE progression ,CHEMORADIOTHERAPY ,SYMPTOMS - Abstract
Primitive neuroectodermal tumor (PNET) is a rare and highly malignant neoplasm composed of small round cells, which frequently occurs in children and adolescents. PNET originating from the prostate is even rarer. We report a case of PNET of the prostate with notalgia and paraplegia as the initial symptoms. Positron emission tomography–computed tomography scanning showed hypodense and hypermetabolism on the prostate; subsequently, we ascertained the diagnosis by transrectal ultrasound-guided biopsy. The patient underwent local vertebral radiotherapy combined with five courses of systematic chemotherapy. Disease progressed after 11 months, and the overall survival was 17 months. [ABSTRACT FROM AUTHOR]
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- 2019
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37. Lymph node metastasis in rectal cancer: comparison of MDCT and MR imaging for diagnostic accuracy.
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Liu, Yiyan, Wen, Ziqiang, Yang, Xinyue, Lu, Baolan, Xiao, Xiaojuan, Chen, Yan, and Yu, Shenping
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RECTAL cancer ,MAGNETIC resonance imaging ,DIAGNOSTIC imaging ,LYMPH nodes ,METASTASIS ,ENDORECTAL ultrasonography - Abstract
Purpose: To compare the diagnostic accuracies of MDCT and high-resolution MRI (HR-MRI) for regional nodal metastases with different short-axis diameter ranges in rectal cancer patients. Methods: Rectal adenocarcinoma patients who underwent both MDCT and HR-MRI before surgery were included. The maximum short-axis diameters of the nodes were measured, and were classified as benign or malignant on imaging findings. All of the nodes were subdivided as follows: ≤ 5 mm (Group A), > 5 mm and ≤ 10 mm (Group B) , and > 10 mm (Group C). The postoperative pathological reports were used as the standard, and the sensitivity, specificity, accuracy, ROC curve, and AUC value were calculated for each subgroup. Results: A total of 592 nodes were included in the node-to-node evaluation. In Group A, the specificity and accuracy of HR-MRI were significantly higher than those of MDCT (99.28% vs. 93.99%, P < 0.001; 95.78% vs. 89.56%, P = 0.010; respectively). In Group B, the specificity and accuracy of HR-MRI were also higher than those of MDCT (98.36% vs. 55.74%, P < 0.001; 80.45% vs. 66.17%, P < 0.001; respectively). For Groups A and B, the AUCs of MDCT were both 0.65, whereas those of HR-MRI were 0.76 and 0.82, respectively. In Group C, all nine malignant nodes were correctly diagnosed metastases on MDCT, whereas one was misjudged as benign on HR-MRI. Conclusions: The diagnostic value of HR-MRI is superior to that of MDCT, with higher specificity, accuracy, and AUC values for HR-MRI than for MDCT. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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38. Clinicopathological characteristics of neck ganglioneuroma
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Chen Yan, Gao Yan, Shang Jian-wei, and Zhang Zebing
- Subjects
Pathology ,medicine.medical_specialty ,biology ,business.industry ,Enolase ,Chromogranin A ,Anatomy ,medicine.disease ,Metastasis ,Ganglion ,Immunophenotyping ,medicine.anatomical_structure ,medicine ,Synaptophysin ,biology.protein ,Immunohistochemistry ,Ganglioneuroma ,business - Abstract
Ganglioneuroma of the head and neck is rare. The clinical, histopathological and immunohistochemical characteristics of 6 cases of cervical ganglioneuroma were analyzed. The average age of the patients in this study was 32.8 years (6-62 years). The tumors grew slowly and the patients were asymptomatic. Grossly, they were well encapsulated. Under the microscope, the tumors consisted of primarily Schwann cells, tangled masses of neurites in bundles, and variably-distributed large ganglion cells. The ganglion cells showed positive immunohistochemical reactivity to neuronspecific enolase, neurofilament, chromogranin A, and synaptophysin but negative for S100, the same as in the controlled normal sublingual ganglion cells. All the tumors were treated with surgical excision. There was no recurrence and metastasis during a follow-up time of 3-5 years.
- Published
- 2008
39. Expression of pyruvate dehydrogenase is an independent prognostic marker in gastric cancer
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Hui-Jing Zhang, Ming-Jun Sun, Xuren Sun, Zhe Sun, Huimian Xu, Yining Zhang, Hai-Xia Guan, Zhi Zhu, Junyan Zhang, Chen-Yan Li, and Huan Zhou
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Adult ,Male ,Pathology ,medicine.medical_specialty ,China ,Time Factors ,Lymphovascular invasion ,Kaplan-Meier Estimate ,Biology ,Metastasis ,Predictive Value of Tests ,Risk Factors ,Stomach Neoplasms ,medicine ,Biomarkers, Tumor ,Humans ,Pyruvate Dehydrogenase (Lipoamide) ,Prospective Studies ,Prospective cohort study ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Aged, 80 and over ,Univariate analysis ,Tissue microarray ,Chi-Square Distribution ,digestive, oral, and skin physiology ,Gastroenterology ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,Pyruvate dehydrogenase complex ,Immunohistochemistry ,digestive system diseases ,Treatment Outcome ,Tissue Array Analysis ,Lymphatic Metastasis ,Multivariate Analysis ,Prospective Study ,Female - Abstract
AIM: To investigate the expression and prognostic role of pyruvate dehydrogenase (PDH) in gastric cancer (GC). METHODS: This study included 265 patients (194 male, 71 female, mean age 59 years (range, 29-81 years) with GC who underwent curative surgery at the First Affiliated Hospital of China Medical University from January 2006 to May 2007. All patients were followed up for more than 5 years. Patient-derived paraffin embedded GC specimens were collected for tissue microarrays (TMAs). We examined PDH expression by immunohistochemistry in TMAs containing tumor tissue and matched non-neoplastic mucosa. Immunoreactivity was evaluated independently by two researchers. Overall survival (OS) rates were determined using the Kaplan-Meier estimator. Correlations with other clinicopathologic factors were evaluated by two-tailed χ2 tests or a two-tailed t-test. The Cox proportional-hazard model was used in univariate analysis and multivariate analysis to identify factors significantly correlated with prognosis. RESULTS: Immunohistochemistry showed that 35.47% of total cancer tissue specimens had cytoplasmic PDH staining. PDH expression was much higher in normal mucosa specimens (75.09%; P = 0.001). PDH expression was correlated with Lauren grade (70.77% in intestinal type vs 40.0% in diffuse type; P = 0.001), lymph node metastasis (65.43% with no metastasis vs 51.09% with metastasis; P = 0.033), lymphatic invasion (61.62% with no invasion vs 38.81% with invasion; P = 0.002), histologic subtypes (70.77% in intestinal type vs 40.0% in diffuse type; P = 0.001) and tumor-node-metastasis (TNM) stage (39% in poorly differentiated vs 65.91% in well differentiated and 67.11% in moderately differentiated; P = 0.001) in GC. PDH expression in cancer tissue was significantly associated with higher OS (P < 0.001). The multivariate analysis adjusted for age, Lauren classification, TNM stage, lymph node metastasis, histological type, tumor size, depth of invasion and lymphatic invasion showed that the PDH expression in GC was an independent prognostic factor for higher OS (HR = 0.608, 95%CI: 0.504-0.734, P < 0.001). CONCLUSION: Our study indicated that PDH expression is an independent prognostic factor in GC patients and that positive expression of PDH may be predictive of favorable outcomes.
- Published
- 2015
40. Shikonin inhibits triple-negative breast cancer-cell metastasis by reversing the epithelial-to-mesenchymal transition via glycogen synthase kinase 3β-regulated suppression of β-catenin signaling.
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Chen, Yan, Chen, Zong-yue, Chen, Lin, Zhang, Jing-yu, Fu, Ling-yun, Tao, Ling, Zhang, Yue, Hu, Xiao-xia, and Shen, Xiang-chun
- Subjects
- *
GLYCOGEN synthase kinase , *GLYCOGEN synthase kinase-3 , *METASTATIC breast cancer , *SHIKONIN , *TRIPLE-negative breast cancer , *CYTOSKELETAL proteins - Abstract
Triple-negative breast cancer (TNBC) is characterized by elevated metastasis, low survival, and poor response to therapy. Although many specific and effective agents for treating TNBC have been investigated, promising therapeutic options remain elusive. Here, we screened the inhibitory activities of three main components of Lithospermum erythrorhizon Sieb. et Zucc (shikonin, acetylshikonin, and β,β-dimethylacrylshikonin) on TNBC cells. The results revealed that shikonin potently decreased the viabilities of TNBC MDA-MB-231 and 4T1 cells but showed less cytotoxicity to normal mammary epithelial MCF-12A cells. Additionally, shikonin reversed the epithelial-to-mesenchymal transition (EMT) in MDA-MB-231 and 4T1 cells. Shikonin depressed cell migration and invasion, upregulated E-cadherin levels, downregulated N-cadherin, vimentin, and Snail levels, and reorganized the cytoskeletal proteins F-actin and vimentin. Shikonin reversed EMT by inhibiting activation of β-catenin signaling through attenuating β-catenin expression, nuclear accumulation, binding to T-cell factor consensus oligos, and transcription of its targeted EMT-related genes. Moreover, shikonin upregulated glycogen synthase kinase 3β (GSK-3β) levels, leading to enhanced phosphorylation and decreased levels of β-catenin. Furthermore, shikonin administration significantly inhibited lung metastasis of MDA-MB-231 cells in NOD/SCID mice accompanied by low systemic toxicity. Histological analysis confirmed that shikonin elevated levels of E-cadherin, phosphorylated β-catenin, and GSK-3β, and decreased levels of vimentin and β-catenin in pulmonary metastatic foci. These results indicated that shikonin potently inhibits TNBC metastasis by targeting the EMT via GSK-3β-regulated suppression of β-catenin signaling, which highlights the importance of shikonin as a potential candidate for novel anticancer therapeutics against TNBC. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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41. Whole-tumour histogram analysis of pharmacokinetic parameters from dynamic contrast-enhanced MRI in resectable oesophageal squamous cell carcinoma can predict T-stage and regional lymph node metastasis.
- Author
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Chen, Yan-li, Li, Rui, Chen, Tian-wu, Ou, Jing, Zhang, Xiao-ming, Chen, Fan, Wu, Lan, Jiang, Yu, Laws, Maxwell, Shah, Kamran, Joseph, Bobby, and Hu, Jiani
- Subjects
- *
CONTRAST-enhanced magnetic resonance imaging , *SQUAMOUS cell carcinoma , *HISTOGRAMS , *LYMPH nodes , *RECEIVER operating characteristic curves , *COMPARATIVE studies , *EPIDEMIOLOGICAL research , *ESOPHAGEAL tumors , *MAGNETIC resonance imaging , *RESEARCH methodology , *MEDICAL cooperation , *METASTASIS , *RESEARCH , *TUMOR classification , *EVALUATION research , *CONTRAST media - Abstract
Objective: To identify whether whole-tumour histogram analysis of pharmacokinetic parameters from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) could predict T-stage and regional lymph node metastasis (LNM) of resectable oesophageal squamous cell carcinoma (SCC).Materials and Methods: Forty-two consecutive patients with confirmed oesophageal SCC underwent thoracic DCE-MRI. Histogram metrics (median, mean, standard deviation [SD], skewness, kurtosis and entropy) of whole-tumour pharmacokinetic parameters including endothelial transfer constant (Ktrans), reflux rate (Kep) and fractional extravascular extracellular space volume (Ve) were generated by the Omni-Kinetics software. Histogram datasets were interpreted using the Mann-Whitney U test and receiver operating characteristic (ROC) statistical analyses.Results: The Mann-Whitney U tests revealed that the median, mean and SD of Ktrans, the SD and entropy of Kep, and the median, mean and entropy of Ve of T1-2 stage oesophageal SCC were lower when compared with T3 stage (all Ps < 0.05); and the ROC analysis showed that the entropy of Ve could reliably distinguish T1-2 stage from T3 stage with an area under ROC (AUC) of 0.773. The Mann-Whitney U tests illustrated that the entropy of Ktrans, and the median, mean, SD and entropy of Kep were higher while the skewness of Kep was lower in tumours with LNM than without LNM (all Ps < 0.05); and the ROC analysis demonstrated that the SD of Kep could best identify tumours with LNM with an AUC of 0.702.Conclusion: Whole-tumour histogram analysis of pharmacokinetic parameters of oesophageal SCC on DCE-MRI could be used to predict T-stage and regional LNM. [ABSTRACT FROM AUTHOR]- Published
- 2019
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42. Renal epithelioid angiomyolipoma: magnetic resonance imaging characteristics.
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Cong, Xinying, Zhang, Jin, Xu, Xiaojuan, Zhang, Miaomiao, and Chen, Yan
- Subjects
MAGNETIC resonance imaging ,ANGIOMYOLIPOMA ,PATHOLOGY ,KIDNEY tumors ,METASTASIS - Abstract
Objective: The aim of the study was to analyze MR imaging features of renal epithelioid angiomyolipoma (EAML).Methods: This study included 17 patients with histopathologically confirmed renal EAML who underwent renal MRI scanning before radical or partial nephrectomy. MR images were retrospectively reviewed and correlated with pathological findings.Result: Fifteen lesions (88.2%) appeared as round or oval. The tumor-kidney interface was round in 14 lesions (82.4%). Fifteen tumors (88.2%) presented mainly isointensity on T1WI, and eleven tumors (64.7%) presented mainly hypointensity on T2WI. Twelve lesions (70.6%) showed restricted diffusion on DWI, and the mean ADC value was 1.23 ± 0.28 × 10
−3 mm2 /s. Minimal fat component was identified as loss of signal intensity on opposed-phase MR images in 6 cases (35.3%). Sixteen lesions (100%) demonstrated inhomogeneous enhancement, and 7 of 16 masses (43.8%) showed reticular enhancement. Rapid wash-in and wash-out enhancement was seen in 13 masses (81.3%). In the corticomedullary phase, the mass showed markedly enhancement in 14 cases (87.5%). The irregular vessels and hemorrhage were detected in 4 cases (23.5%) and 7 cases (41.2%), respectively. One patient (5.9%) had a lymph node involvement at initial diagnosis, and showed distant metastasis after operation. In the immunohistochemical analysis, 15 tumors (88.2%) were positive for melanocytic marker (HMB45 or Melan-A), and all cases (100%) were negative for epithelial-associated markers (CK or AE1/AE3).Conclusion: The presence of hypointensity on T2WI, restricted diffusion on DWI, round tumor-kidney interface, reticular, and marked enhancement (rapid wash-in and wash-out) should further raise suspicion for renal EAML. The diagnosis may be confirmed by pathological analysis. [ABSTRACT FROM AUTHOR]- Published
- 2018
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- View/download PDF
43. Ubiquitin-like protein FAT10 promotes the invasion and metastasis of hepatocellular carcinoma by modifying β-catenin degradation
- Author
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Junwen Hu, Xiuxia Liu, Xin Yu, Kui Hong, Wuhua Guo, Chen Yan, Rongfa Yuan, Jun Lei, Jianghua Shao, Linquan Wu, Kai Wang, and Ming Li
- Subjects
Male ,Cancer Research ,Carcinoma, Hepatocellular ,Mice, Nude ,Transfection ,Metastasis ,Mice ,Transcription Factor 4 ,Ubiquitin ,Cell Line, Tumor ,medicine ,Carcinoma ,Gene silencing ,Animals ,Humans ,Neoplasm Invasiveness ,Neoplasm Metastasis ,Ubiquitins ,beta Catenin ,Homeodomain Proteins ,Mice, Inbred BALB C ,biology ,Chemistry ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,Liver Neoplasms ,Cancer ,TCF4 ,Middle Aged ,medicine.disease ,digestive system diseases ,Oncology ,Hepatocellular carcinoma ,Catenin ,Cancer research ,biology.protein ,Heterografts ,Female ,Transcription Factors - Abstract
The ubiquitin-like protein FAT10 and the homeobox protein HOXB9 each promote metastatic progression in hepatocellular carcinoma (HCC). In this study, we investigated the clinicopathologic significance of FAT10 and HOXB9 in HCC and investigated a mechanistic role for FAT10 in HOXB9-mediated invasiveness and metastasis. Relative to adjacent normal tissues, FAT10 and HOXB9 were markedly overexpressed in HCC, where a positive correlation in their expression and associated malignant characteristics were found. RNAi-mediated silencing of FAT10 decreased HOXB9 expression and inhibited HCC invasion and metastasis in vitro and in vivo. The effects of FAT10 silencing were reversed by HOXB9 overexpression, whereas RNAi-mediated silencing of HOXB9 decreased HCC invasion and metastasis driven by FAT10 overexpression. Mechanistically, FAT10 regulated HOXB9 expression by modulating the β-catenin/TCF4 pathway, directly binding to β-catenin and preventing its ubiquitination and degradation. Together, our results identified a novel HCC regulatory circuit involving FAT10, β-catenin/TCF4, and HOXB9, the dysfunction of which drives invasive and metastatic character in HCC. Cancer Res; 74(18); 5287–300. ©2014 AACR.
- Published
- 2014
44. Correction to: SNCG promotes the progression and metastasis of high-grade serous ovarian cancer via targeting the PI3K/AKT signaling pathway.
- Author
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Zhang, Jing, Liu, Xiao-han, Li, Cong, Wu, Xiao-xing, Chen, Yan-lin, Li, Wen-wen, Li, Xian, Gong, Fan, Tang, Qin, and Jiang, Dan
- Subjects
OVARIAN cancer ,METASTASIS - Abstract
An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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45. Establishment of a Gallbladder Cancer-Specific Survival Model to Predict Prognosis in Non-metastatic Gallbladder Cancer Patients After Surgical Resection.
- Author
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Zhang, Woods, Hong, H. J., and Chen, Yan-ling
- Subjects
GALLBLADDER cancer ,EPIDEMIOLOGY ,METASTASIS ,CANCER chemotherapy ,PROGNOSIS - Abstract
Background: Gallbladder cancer is an invasive cancer with a discouraging prognosis, and early detection and active intervention are of great value.Aims: To establish a more accurate and effective survival model to predict the prognosis of patients with non-metastatic gallbladder after surgical resection.Methods: A retrospective analysis was conducted in non-metastatic gallbladder cancer patients who were registered in the surveillance, epidemiology and end results database from 2010 to 2014. Univariate analysis and multivariate analysis were performed for the related factors that might affect the gallbladder cancer-specific survival. A prognostic gallbladder cancer-specific survival model was established using the nomogram tool. The discrimination test was measured by the c-index, and the conformance test was performed by a calibration curve.Results: In all, 1422 patients with non-metastatic gallbladder cancer were identified. The prognostic factors include age, gender, lymph node dissection, postoperative chemotherapy, tumor size, histological grading, pT stage and pN stage. The gallbladder cancer-specific survival model was established based on the prognostic factors. The model's c-index was 0.775, and the 7th AJCC staging c-index was 0.649. The calibration curves showed a good correlation between prediction and actual survival.Conclusions: This study established the gallbladder cancer-specific survival model successfully. Compared with the 7th AJCC stage, this model refined the contribution of the pT stage, pN stage and other related factors and was demonstrated to be more accurate and reliable. More importantly, this model may allow clinicians to screen patients with a poor prognosis for closer follow-up or adjuvant treatment. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
46. Prostate Cancer Disseminated Tumor Cells are Rarely Detected in the Bone Marrow of Patients with Localized Disease Undergoing Radical Prostatectomy across Multiple Rare Cell Detection Platforms.
- Author
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Chalfin, Heather J., Glavaris, Stephanie A., Malihi, Paymaneh D., Sperger, Jamie M., Gorin, Michael A., Lu, Changxue, Goodwin, C. Rory, Chen, Yan, Caruso, Emily A., Dumpit, Ruth, Kuhn, Peter, Lang, Joshua M., Nelson, Peter S., Luo, Jun, and Pienta, Kenneth J.
- Subjects
PROSTATE cancer patients ,PROSTATECTOMY ,BONE marrow cancer ,CANCER cells ,METASTASIS ,DIAGNOSIS - Abstract
Purpose Prostate circulating tumor cells escape into peripheral blood and enter bone marrow as disseminated tumor cells, representing an early step before conventionally detectable metastasis. It is unclear how frequently this occurs in localized disease and existing detection methods rely on epithelial markers with low specificity and sensitivity. We used multiple methodologies of disseminated tumor cell detection in bone marrow harvested at radical prostatectomy. Materials and Methods Bone marrow was harvested from 208 clinically localized cases, 16 controls and 5 metastatic cases with peripheral blood obtained from 37 metastatic cases. Samples were evaluated at 4 centers with 4 distinct platforms using antibody enrichment with the AdnaTest (Qiagen®) or VERSA (versatile exclusion based rare sample analysis), or whole sample interrogation with the RareCyte platform (Seattle, Washington) or HD-SCA (high definition single cell assay) using traditional epithelial markers and prostate specific markers. We investigated the sensitivity and specificity of these markers by evaluating expression levels in control and metastatic cases. Results EpCAM , NKX3.1 and AR were nonspecifically expressed in controls and in most samples using AdnaTest with no relation to perioperative variables. Only 1 patient with localized disease showed positive results for the prostate specific marker PSA . With the VERSA platform no localized case demonstrated disseminated tumor cells. With the RareCyte and HD-SCA platforms only a single patient had 1 disseminated tumor cell. Conclusions Evaluation across multiple platforms revealed that epithelial markers are nonspecific in bone marrow and, thus, not suitable for disseminated tumor cell detection. Using prostate specific markers disseminated tumor cells were typically not detected in patients with localized prostate cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
47. LDH-A promotes epithelial-mesenchymal transition by upregulating ZEB2 in intestinal-type gastric cancer.
- Author
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Zhang, Yongjie, Lin, Sen, Chen, Yan, Yang, Fei, and Liu, Shenlin
- Subjects
LACTATE dehydrogenase ,INTESTINAL cancer ,METASTASIS ,CANCER relapse ,CANCER-related mortality ,HYPOXEMIA - Abstract
Introduction: Epithelial-mesenchymal transition (EMT) is regarded as a crucial process of invasion and metastasis, which contribute greatly to cancer-related relapse and death. Based on research results that hypoxia can trigger gastric cancer EMT and decreasing lactate production can selectively kill hypoxic cancer cells, we infer that lactate dehydrogenase A (LDH-A) transforming pyruvate into lactate is at least in part responsible for poor prognosis of gastric cancer. Materials and methods: We used siRNA to knock down LDH-A in intestinal-type gastric cancer (ITGC) cell lines SGC7901 and BGC823. Western blot and RT-PCR were applied to detect mRNA and protein expression of EMT-related genes, respectively. Transwell invasion assay and migration assay were applied to study invasive and migratory abilities, respectively. Survival analysis was used to evaluate prognostic values. Results and conclusion: The results of in vitro experiment demonstrated that LDH-A facilitates ITGC cells' invasion and migration by upregulating ZEB2. The positive correlation between LDH-A and ZEB2 was verified in 371 ITGC specimens. Survival analysis indicated that co-expression of LDH-A/ZEB2 had synergetic power to predict overall survival. Thus, we conclude that the close relationship between LDH-A and ZEB2 may offer a potential therapeutic strategy for ITGC. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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48. Identification of dysregulated lnc RNAs profiling and metastasis-associated lnc RNAs in colorectal cancer by genome-wide analysis.
- Author
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Chen, Yan, Yu, Xiang, Xu, Yongcan, and Shen, Hua
- Subjects
- *
GENETICS of colon cancer , *COLON cancer patients , *NON-coding RNA , *RNA sequencing , *NEOPLASTIC cell transformation - Abstract
The colorectal cancer ( CRC) is one of the leading causes of cancer-related death worldwide, but the pathogenesis of CRC remains not well-known. Increasing studies have highlighted the critical roles of long noncoding RNAs (lnc RNAs) in tumorigenesis and cancer cells metastasis, however, the expression pattern, biological roles of lnc RNAs, and the mechanisms responsible for their function in CRC remain elusive. In this study, we performed a genome-wide comprehensive analysis of lnc RNAs profiling and clinical relevance to identify novel lnc RNAs for the further study in CRC. RNA sequencing and microarray data obtained from The Cancer Genome Atlas ( TCGA) and Gene Expression Omnibus ( GEO) were annotated and analyzed to find differentially expressed lnc RNAs in CRC. Analysis of these datasets revealed that hundreds of lnc RNAs expression are dysregulated in CRC tissues when compared with normal tissues. By genomic variation analyses, we identified that some of these lnc RNAs dysregulation is associated with the copy number amplification or deletion. Moreover, many lnc RNAs expression levels are significantly associated with CRC patients overall and recurrence-free survivals, such as H19, LEF1- AS1, and RP11-296E3.2. Furthermore, we identified one liver metastasis-associated lnc RNA termed LUCAT1 in CRC by analyzing lnc RNAs expression profiles in the CRC tissues from patients with liver metastasis compared with the CRC tissues without metastasis. Finally, loss-of-function assays determined that knockdown of LUCAT1 could impair CRC cells invasion. Taken together, aberrantly expressed lnc RNAs may play critical roles in the development and liver metastasis of CRC, and our findings may provide useful resource for identification of novel biomarkers of CRC. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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49. Comparison of the c-MET gene amplification between primary tumor and metastatic lymph nodes in non-small cell lung cancer.
- Author
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Xu, Chun‐wei, Wang, Wen‐xian, Wu, Mei‐juan, Zhu, You‐cai, Zhuang, Wu, Lin, Gen, Du, Kai‐qi, Huang, Yun‐jian, Chen, Yan‐ping, Chen, Gang, and Fang, Mei‐yu
- Subjects
LUNG cancer diagnosis ,GENE amplification ,LUNG cancer ,LYMPH nodes ,METASTASIS ,ONCOGENES ,POLYMERASE chain reaction ,PROTEIN-tyrosine kinases ,GENETIC testing ,CANCER of unknown primary origin - Abstract
Background c-MET has recently been identified as a promising novel target in non-small cell lung cancer ( NSCLC). We detected the consistency of c-MET gene amplification in metastatic lymph nodes and tumor tissues of NSCLC patients and discuss the clinical application value of c-MET gene amplification in metastatic lymph nodes. Methods Real-time fluorescent quantitative PCR was used to test tumor tissues in 368 NSCLC patients and 178 paired metastatic lymph node samples. The amplification consistency in metastatic lymph nodes and tissue samples were compared and the correlation between c-MET gene amplification and the clinical characteristics of patients was analyzed. Results The c-MET gene amplification rate was 8.97% (33/368) in tumor tissues. Of the 178 paired cases, c-MET gene amplification was positive in 7.95% (15/178) of cancerous tissues and 18.54% (33/178) of metastatic lymph nodes. c-MET gene amplification was detected more frequently in metastatic lymph nodes than in primary cancerous tissue. When metastatic lymph nodes were used as surrogate samples of primary cancerous tissues, the sensitivity was 86.67% (13/15) and the specificity was 87.69% (143/163). Conclusions Screening for c-MET gene amplification in lymph node metastases could determine which patients are eligible for tyrosine kinase inhibitor therapy. Lymph node metastasis can predict c-MET gene amplification in a primary tumor and guide the clinical use of c-MET gene targeted drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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50. [Antitumor effects of soluble TRAIL in human hepatocellular carcinoma]
- Author
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Chen Xiaoping, Zhang Wanguang, Wang Haiping, Chen Yan, Wang Shaofa, Zhao Yongzhong, and He Songqing
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Adolescent ,Angiogenesis ,Biomedical Engineering ,Antineoplastic Agents ,Apoptosis ,Biochemistry ,Jurkat cells ,Receptors, Tumor Necrosis Factor ,Metastasis ,Flow cytometry ,Biomaterials ,TNF-Related Apoptosis-Inducing Ligand ,Cell Line, Tumor ,Internal medicine ,Genetics ,medicine ,Carcinoma ,In Situ Nick-End Labeling ,Humans ,Receptor ,neoplasms ,Earth-Surface Processes ,Aged ,Membrane Glycoproteins ,medicine.diagnostic_test ,Tumor Necrosis Factor-alpha ,business.industry ,Liver Neoplasms ,Hep G2 Cells ,Middle Aged ,medicine.disease ,digestive system diseases ,Receptors, TNF-Related Apoptosis-Inducing Ligand ,Hepatocellular carcinoma ,Cancer research ,Female ,Apoptosis Regulatory Proteins ,business - Abstract
The therapeutic potential of soluble TRAIL (sTRAIL) in hepatocellular carcinoma (HCC) was studied. The expression of TRAIL receptors was detected in 60 HCC tissues, 20 normal liver samples and 2 HCC cell lines (HepG2 and SMMC-7721) by in situ hybridization. Before and after HepG2 and SMMC-7721 were treated with sTRAIL protein with various concentrations, the apoptosis rate was observed by using flow cytometry and in situ terminal deoxynucleotidyl tranferase (TdT) labeling. The results showed death receptor 4 (DR4) and DR5 were expressed in 60 HCC tissues and 20 normal liver samples, while the expression intensity of DR in HCC tissues was stronger than in normal liver samples. DcR1 and DcR2 were not detectable in 54 (90%) and 25 (41.%) HCC tissues, while in 20 normal liver samples, DcR was detectable. The high expression of DR and low expression of DcR in HCC tissues were significantly differed from the low expression and high expression in normal liver samples. The expression of DR5, DR4 and DcR2 in both HCC cell lines was detectable, but the expression of DcR1 was not detectable. The expression of DR in HCC tissues was related to the differentiation and grades of HCC. In the poor differentiated HCC, the expression of DR was decreased (P0.01). The expression of DR in Il/IV grades was significantly lower than that in I / 11 grades (P0.05). The expression of DR was not related to gender, age, HBsAg, AFP, tumor size and metastasis. The expression of DR in the HCC drugresistant lines was decreased. After treatment with TRAIL (100 ng/ml) for 24 h, the apoptosis rate of HCC cells, Jurkat cells and human cholangiocarcinoma cell line QBC939 was 10%, 70%, 50% respectively. It was suggested that the TRAILR expression is prevalent in HCC with different expression patterns of different receptor types. HCC is resistant to TRAIL-mediated apoptosis. The treatment of TRAIL alone has a limited effect on inducing apoptosis of HepG2 and SMMC7721.
- Published
- 2003
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