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Tumor-associated macrophages (TAMs) are an important part of tumor microenvironment (TME) and play a key role in TME, participating in the process of tumor occurrence, growth, invasion, and metastasis. Among them, metastasis to tumor tissue is the key step of malignant development of tumor. In this paper, the latest progress in the role of TAMs in the formation of tumor microenvironment is summarized. It is particularly noteworthy that cell and animal experiments show that TAMs can provide a favorable microenvironment for the occurrence and development of tumors. At the same time, clinical pathological experiments show that the accumulation of TAMs in tumor is related to poor clinical efficacy. Finally, this paper discusses the feasibility of TAMs-targeted therapy as a new indirect cancer therapy. This paper provides a theoretical basis for finding a potentially effective macrophage-targeted tumor therapy. [ABSTRACT FROM AUTHOR]

This paper explores the relationship between the clinical value of vasodilator-stimulated phosphoprotein (VASP) in lung cancer tissue and its diagnosis and severity. Totally 100 patients who were clinically diagnosed with lung cancer from January 2018 to December 2020 were enrolled in our study. They were assigned into two groups according to the presence of lymph node metastasis. The VASP levels were measured by flow cytometry. The correlation between the expression of VASP in tumor tissue and the clinical characteristics and prognosis in patients was analyzed. The diagnostic efficacy of plasma VASP with squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), cytokeratin-19 fragment (CYFRA21-1), prosecretin-releasing peptide (proGRP), and lung cancer was analyzed. The results were compared with APACHE III score to evaluate the accuracy of VASP in determining the severity of patients. This paper finds that the value of VASP in the non-lymph node metastasis group was significantly higher than that in the healthy control group, and the VASP level in the lymph node metastasis group was significantly higher than that in the non-lymph node metastasis group and the healthy control group (all p values <0.05). The APACHE III score of the lymph node metastasis group was higher than that of the non-lymph node metastasis group (p value <0.05). The diagnostic efficacy of VASP is similar to that of SCC, NSE, CYFRA21-1, and proGRP. The plasma VASP value was statistically different in the survival group and the death group, with higher level observed in the death group compared to survival group (all p values <0.05). The value of plasma VASP alone and acute physiology and chronic health evaluations III (APACHE III) score for lung cancer mortality was similar (47.06% vs. 52.94%, p value >0.05). Similar accuracy was observed in VASP and APACHE III score in predicting mortality of lung cancer (84.37% vs. 85.77%, p value>0.05). This paper concludes that the level of VASP correlates to the severity of the lung cancer and survival of the patients. [ABSTRACT FROM AUTHOR]

To investigate trends in long-noncoding (lnc) RNA research systematically, we compared the contribution of publications among different regions, institutions, and authors. Publications on lncRNA were retrieved from Web of Science (WoS) from 1975 to 2017. A total of 3879 papers were identified, and together they were cited 62967 times. The literature on lncRNA had been continuously growing since 2006, and the expansion might continue at a rapid pace until around 2021. China contributed the greatest proportion (63.47%) of lncRNA publications, and the USA ranked second in the number of publications (944 articles), while it had the highest citation frequency (43168 times) and H-index (97). The journal Oncotarget has the greatest number of publications on lncRNA research, with 305 papers. The keywords could be stratified into two clusters: cluster 1 (application) and cluster 2 (characteristics). Correspondingly, the “TNM stage,” “epithelial mesenchymal transition (EMT),” “cell apoptosis,” and “overall survival” are research hotspots since 2015. Thus, research on lncRNA showed a swiftly expanding trend, with China making the largest contribution. The focus on lncRNA is gradually shifting from “characteristics” to “application.” [ABSTRACT FROM AUTHOR]

A large number of facts have shown that epigenetic modification and metabolic reprogramming represented by noncoding RNA play an important role in the invasion and metastasis of breast cancer, but the mechanism is not clear. The purpose of our study is to find a new biomarker of breast cancer and to provide a new perspective for regulating glucose metabolism and aerobic glycolysis of BC. In this paper, by downregulating C-myc protein, our team found that the expression of long-chain noncoding RNATSPAR-AS2 was significantly downregulated. However, the expression of long-chain noncoding RNASPAR-AS2 in BC is relatively high, and the prognosis is poor. TSPEAR-AS2 can promote the malignant phenotype of BC cells, including proliferation, apoptosis, invasion and metastasis, and glycolysis. At the same time, TSPEAR-AS2 can also upregulate the expression of GLUT1, an important regulator of glycolysis, thus promoting the metabolic reprogramming of BC. Molecular mechanism experiments show that TSPEAR-AS2 may promote the expression of GLUT1 by participating in IGF2BP2 modified by the GLUT1 gene. Our results suggest that the C-myc/TSPEAR-AS2/GLUT1 axis promotes the invasion and metastasis of BC by inducing glucose metabolism reprogramming. However, more phenotypic and molecular mechanism results need to be further verified. [ABSTRACT FROM AUTHOR]

The paper is written to investigate the levels and significance of tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), and carbohydrate antigen 19-9 (CA19-9)] and cytokines [interleukin-6 (IL-6), IL-4, and IL-2] in serum and peritoneal lavage fluid of patients with peritoneal metastasis of gastric cancer. For this research, 145 patients with gastric cancer treated in our hospital were divided into peritoneal metastasis group (n = 25), other metastasis group (n = 32), and nonmetastasis group (n = 88) according to the occurrence of metastasis. At the same time, the levels of serum tumor markers and cytokines and tumor markers and cytokines in intraoperative peritoneal lavage fluid were compared among the three groups. The results showed that the proportion of TNM stage III in peritoneal metastasis group and other metastasis group was 68.00% and 62.50%, respectively, and the proportion of tumor >5 cm was 64.00% and 59.38%, respectively, which was significantly higher than that in the control group. The 1-year survival rate of peritoneal metastasis group and other metastasis group was 44.00% and 40.63%, respectively, which was significantly lower than that of nonmetastasis group (P < 0.05).The serum levels of CEA, CA125, CA19-9, IL-6, IL-4, and IL-2 in peritoneal metastasis group and other metastasis group were higher than those in nonmetastasis group. The intraoperative peritoneal lavage fluid CEA, CA125, and IL-6 were 13.41 ± 3.72 ng/ml, 8.97 ± 1.33 U/ml, and 1.85 ± 0.44 pg/ml, respectively, which were higher than those in other metastasis groups and nonmetastasis groups (P < 0.05). There was no significant difference in the levels of CA19-9, IL-4, and IL-2 in peritoneal lavage fluid among peritoneal metastasis group, other metastasis groups, and nonmetastasis groups (P > 0.05); the areas under the ROC curve of intraoperative peritoneal lavage fluid CEA, CA125, and IL-6 in predicting peritoneal metastasis were 0.850, 0.902, and 0.806, respectively, P < 0.05. Thus, the conclusion is that peritoneal lavage fluid CEA, CA125, and IL-6 have certain application value in predicting and diagnosing peritoneal metastasis of gastric cancer, while the other indexes have no application value. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma is the most common non-small-cell lung cancer. In this paper, we aim to investigate the expression of chemokine ligand 1 (cx3cl1) and chemokine ligand 28 (CCL28) in spinal metastases of lung adenocarcinoma and their correlation with clinical features and prognosis. We analyzed the clinical data of 40 patients with lung adenocarcinoma and spinal metastases who underwent surgery in our hospital from January 2018 to January 2021 retrospectively. The expression levels of cx3cl1 and CCL28 in bone metastases were detected by immunohistochemistry, and the staining results were sorted and classified. Combined with the follow-up results and clinicopathological data, we statistically analyzed the expression of cx3cl1 and CCL28 in spinal bone metastases and their correlation with prognosis. Among the 40 patients with spinal metastasis of lung adenocarcinoma, 7 cases were strongly positive for cx3cl1, 25 cases were moderately positive, and 8 cases were weakly positive and negative. CCL28 was strongly positive in 9 cases, moderately positive in 26 cases, weakly positive and negative in 5 cases. The expression of cx3cl1 was correlated with ECOG score (P = 0.005) and visceral organ metastasis (P = 0.004), but not with age, sex, and the number of bone metastases (P > 0.05). The expression of CCL28 was correlated with ECOG score (P = 0.022) and visceral organ metastasis (P = 0.003), but not with age, sex, and the number of bone metastases (P > 0.05). The OS of patients with strong cx3cl1 positive was significantly shorter than that of patients with medium positive and weak positive (P < 0.001). The survival time was 10, 7, and 4 months, respectively. The OS of patients with strong positive CCL28 was significantly shorter than that of patients with medium positive and weak positive CCL28 (P = 0.004). The survival time was 12, 8, and 4 months, respectively. Univariate analysis showed that ECOG score (P < 0.001), chemotherapy (P = 0.032), visceral organ metastasis (P = 0.002), cx3cl1 expression (P < 0.001), and CCL28 expression (P = 0.004) were the risk factors of OS. Cox regression analysis showed that the expression of cx3cl1 was an independent risk factor for OS in patients with spinal metastasis of lung adenocarcinoma (P = 0.044). Cx3cl1 and CCL28 were highly/strongly positive in spinal metastases of lung adenocarcinoma. The level of cx3cl1 can be used as an index to judge the clinical prognosis of patients with spinal metastasis of lung adenocarcinoma, which can better reflect the prognosis of patients than CCL28. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the authors' discuss cancer cells, metastasis and cell proliferation.

Purpose. To present a comprehensive review of the literature data, published between 2000 and 2019 on the PubMed and Web of Science databases, in the field of the tumor microenvironment in hepatocellular carcinoma (HCC). All the data were combined with the personal experiences of the authors. Design. From 1002 representative papers, we selected 86 representative publications which included data on epithelial-to-mesenchymal transition (EMT), angiogenesis, cancer stem-like cells (CSCs), and molecular background of chemoresistance or resistance to radiotherapy. Results. Although the central event concerns activation of the Wnt/β-catenin pathway, other signal pathways, such as c-Met/HGF/Snail, Notch-1/NF-κB, TGF-β/SMAD, and basic fibroblast growth factor-related signaling, play a role in the EMT of HCC cells. This pathway is targeted by specific miRNAs and long noncoding RNAs, as explored in this paper. A central player in the tumor microenvironment proved to be the CSCs which can be marked by CD133, CD44, CD90, EpCAM, and CD105. CSCs can induce resistance to cytotoxic therapy or, alternatively, can be synthesized, de novo, after chemo- or radiotherapy, especially after transarterial chemoembolization- or radiofrequency ablation-induced hypoxia. The circulating tumor cells proved to have epithelial, intermediate, or mesenchymal features; their properties have a critical prognostic role. Conclusion. The metastatic pathway of HCC seems to be related to the Wnt- or, rather, TGFβ1-mediated inflammation-angiogenesis-EMT-CSCs crosstalk link. Molecular therapy should target this molecular axis controlling the HCC microenvironment. [ABSTRACT FROM AUTHOR]

Tumor is the most serious threat to human beings. Although war against cancer has been launched over forty years, cancer treatment is still far away from being satisfactory. Immunotherapy, especially checkpoint blockade immunotherapy, is a rising star that shows a promising future. To fulfill the requirement of depleting primary tumor and inhibiting tumor metastasis and recurrence, many researchers combined checkpoint blockade immunotherapy with other treatment strategies to extend the treatment outcome. Photodynamic therapy could induce immunogenic cell death, and checkpoint blockade could further accelerate the immunity; therefore, combining these two strategies publishes many papers. Additionally, photothermal therapy and immunotherapy were also utilized for combining with checkpoint blockade, which were also reviewed in this paper. Furthermore, antibodies, siRNA, and small molecule inhibitors are developed to block the checkpoint; therefore, we categorized the papers into three sections, combination nanoparticles with checkpoint blockade antibody, combination nanoparticles with checkpoint blockade siRNA, and combination nanoparticles with small molecule checkpoint inhibitors, and related researches were summarized. In conclusion, the combination nanoparticle with checkpoint blockade cancer immunity is a promising direction that may fulfill the requirement of cancer treatment. [ABSTRACT FROM AUTHOR]

Skin cancer is a typical cancer tumor, which occurs all over the world and has a relatively high recurrence rate, including metastatic tumors that occur in other tissues and metastases to the skin, thus jeopardizing the personal life satisfaction and soundness of patients. Due to individual differences, the traditional treatment methods cannot adapt to every patient accurately, so it is difficult to achieve the desired treatment effect for each individual. Nowadays, with the development of gene chip, many new therapies based on gene are more targeted and flexible for the treatment of skin cancer patients. Therefore, it is necessary to mine and analyze appropriate gene biomarkers according to patients' genes. Because of the high cost of gene chip technology and the large number of human genes, there are few samples of gene data and high dimensions. It is a key problem to mine effective genetic biomarkers from the sample data. In this paper, we firstly performed the preliminary analysis using the difference expression analysis and proportional hazards model, then used the elastic network method to reduce the range of genetic data selection, and screened 26 gene prognostic markers closely related to the recurrence of metastatic skin cancer. Finally, the 26 gene biomarkers were analyzed by functional analysis and verified using a test sample. Research findings have shown that the obtained genetic markers have certain value in the clinical prognostic treatment of metastatic skin cancer. [ABSTRACT FROM AUTHOR]

Highlights from the article: Most of the work has been dedicated to understand the importance and significance of cancer metastasis and the clinical therapeutic proteins targeted for potential translational implications. A series of three review papers, one from Portugal titled "Liver Metastases and Histological Growth Patterns: Biological Behavior and Potential Clinical Implications - Another Path to Individualized Medicine?" Uniformly, all authors highlight both the promise and the challenges faced by clinicians and basic medical scientists in the emerging field of cancer metastasis.

Background and Aim: Gastric cancer (GC) is the common leading cause of cancer-related death worldwide. Immune-related genes (IRGs) may potentially predict lymph node metastasis (LNM). We aimed to develop a preoperative model to predict LNM based on these IRGs. Methods: In this paper, we compared and evaluated three machine learning models to predict LNM based on publicly available gene expression data from TCGA-STAD. The Pearson correlation coefficient (PCC) method was utilized to feature selection according to its relationships with LN status. The performance of the model was assessed using the area under the curve (AUC) and F1 score. Results: The Naive Bayesian model showed better performance and was constructed based on 26 selected gene features, with AUCs of 0.741 in the training set and 0.688 in the test set. The F1 score in the training set and test set was 0.652 and 0.597, respectively. Furthermore, Naive Bayesian model based on 26 IRGs is the first diagnostic tool for the identification of LNM in advanced GC. Conclusion: These results indicate that our new methods have the value of auxiliary diagnosis with promising clinical potential. [ABSTRACT FROM AUTHOR]

Sentinel lymph node biopsy (SLNB) is a standard in diagnostic and therapeutic management of patients with nonadvanced invasive breast cancer. The aim of this paper was to evaluate the clinical importance of the failure of sentinel lymph node (SLN) identification during SLNB performed to spare axillary lymph nodes. A total of 5396 patients with invasive breast cancer qualified for SLNB, treated in a period from Jan 2004 to June 2018. All cases of the failure of SLN identification and reasons underlying this situation were analyzed retrospectively. In 196 (3.6%) patients, SLN was not identified (group I), and this resulted in a simultaneous axillary lymph node dissection. 48.5% patients from this group were diagnosed with cancer metastases to lymph nodes (vs 23.6% patients with SLN removed—group II, P <.00001)—stage pN1 in 44.2% of the cases, stage pN2 in 22.1% of the cases, and pN3 in 33.7% (in group II—73.4%, 19.5% and 7.1%, respectively), with a presence of extracapsular infiltration in 68.4% patients (vs 41.7% in group II) and with a significantly higher percentage of micrometastatic nature in group II (17.0%, vs 3.2% in group I). The failure of intraoperative sentinel lymph node mapping indicates a significantly increased risk of breast cancer metastases to the axillary lymph system. At the same time, it can also indicate higher cancer stage and its increased aggressiveness. For this reason, in such situation performance of axillary lymph node dissection still appears to be the approach most advantageous for patients. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editors discuss various reports within the issue on topics including the meta-analysis on the imaging modalities for the detection of cutaneous malignant melanoma (CMM) by Y. Xing and colleagues, CMM serum biomarkers by P. Vereecken and colleagues, and migration process of CMM cells by P. Quatresooz and colleagues.

What is known and objective To review the pharmacology, efficacy, safety, formulary and economic considerations of pembrolizumab, a novel, first-in-class, anti- PD-1 monoclonal antibody for treatment of advanced melanoma. Methods A literature search was conducted using PubMed (July 2013-December 2014) with search terms: pembrolizumab, MK-3475 and lambrolizumab. Additional sources were identified through a subsequent review of all relevant papers, clinicaltrials.gov, product labelling and media releases. All English-language studies conducted in humans with clinical data were included. Review papers were excluded from analysis. Results and discussion Patients with advanced melanoma have limited options available. Immune therapies have shown promise in treating advanced melanoma, but can have significant toxicities. Identification of the role of PD-1 in tumour immune evasion and the subsequent development of pembrolizumab, a novel agent that inhibits PD-1, has led to the availability of an additional treatment option for patients who have progressive disease despite treatment with currently approved agents. Phase I cohort studies have demonstrated promising overall response rates and an estimated progression-free survival of approximately 5·5 months. Minimal toxicity has been observed in patients receiving pembrolizumab, although significant severe immune-mediated reactions have been reported. What is new and conclusion Pembrolizumab is a novel anti- PD-1 monoclonal antibody that is an effective option for advanced melanoma previously treated with agents such as ipilimumab and BRAF inhibitors. Additional studies will provide the necessary data for determining its true place in therapy for advanced melanoma and exploring its efficacy in additional malignant indications. [ABSTRACT FROM AUTHOR]

Cancer develops as a result of the loss of self-control mechanisms by a cell; it gains the ability to induce angiogenesis, becomes immortal and resistant to cell death, stops responding to growth suppressor signals, and becomes capable of invasion and metastasis. Sphingolipids—a family of membrane lipids—are known to play important roles in the regulation of cell proliferation, the response to chemotherapeutic agents, and/or prevention of cancer. Despite the underlying functions of sphingolipids in cancer biology, their metabolism in different malignant tumors is poorly investigated. Some studies showed marked differences in ceramide content between the tumor and the respective healthy tissue. Interestingly, the level of this sphingolipid could be either low or elevated, suggesting that the alterations in ceramide metabolism in cancer tissue may depend on the biology of the tumor. These processes are indeed related to the type of cancer, its stage, and histology status. In this paper we present the unique roles of bioactive sphingolipid derivative in selected gynecologic malignant and nonmalignant lesions. [ABSTRACT FROM AUTHOR]

Teratomas are rarely seen in adults, and presacral region is an area where they rarely settle in. Similarly, only about 1% of teratomas show malignant transformation. Malignant transformation is often associated with the area where teratoma settles in. Malignant transformation of mediastinal teratomas is more frequent than the ones located in retroperitoneal area and gonad. They most commonly show rhabdomyosarcoma, primitive neuroectodermal tumor, enteric adenocarcinoma, and leukemia transformation. In teratomas showing malignant transformation, the clinical course is aggressive; and survival of patients with metastatic disease is very low. The primary treatment of teratomas with malignant transformations is surgical. Effect of radiotherapy and chemotherapy is not clear in patients, to whom surgical operation cannot be applied, or those who are with residual tumor, even if surgical operation can be applied to them, or those who are at metastatic stage. In this paper, we presented a 76-year-old male patient due to the histologic diagnosis of mucinous adenocarcinoma within teratoma, in whom approximately 7 cm presacral mass was found during the radiographic examination made by the reason of low back pain and pelvic pain. [ABSTRACT FROM AUTHOR]

Antioxidants are known to be beneficial to health. This paper evaluates the potential chemopreventive and anticancer properties of phenolic compounds present in grape juice extracts (GJE) from Autumn Royal and Ribier varieties. The effects of these GJE on viability (SRB day assay) and metastatic potential (migration and invasion parameters) of colon cancer cell lines HT-29 and SW-480 were evaluated. The effects of GJE on two matrix metalloproteinase gene expressions (MMP2 and MMP9) were also evaluated via qRT-PCR. In the former, GJE reduced cell viability in both cell lines in a dose-dependent manner. GJE treatment also reduced cell migration and invasion. Moreover, MMP-2 and MMP-9 gene expression diminished depending on extract and on cell type. Conclusions. These results provide novel information concerning anticancer properties of selected GJE by revealing selective cytotoxicity and the ability to reduce invasiveness of colon cancer cells. [ABSTRACT FROM AUTHOR]

With more patients with metastatic breast cancer ( MBC) living longer, patient-centered communication and shared decision making between patient and oncologist are vital to improve care and quality of life in patients with MBC. The Make Your Dialogue Count survey explored emotional needs of patients at initial diagnosis of MBC and treatment change to increase awareness about gaps and facilitate communication between patients and oncologists. The survey was conducted (June-August 2014) online, by telephone, or on paper among US women with MBC and US-licensed medical oncologists. Patient data were unweighted. Oncologist data were weighted by geographic region and years in practice by sex to match actual proportions in the population. Statistically significant differences between groups were determined by standard t-test of column proportions and means at the 95% confidence level. Between initial diagnosis of MBC and treatment change, some patients' attitudes and feelings adapted as their disease advanced. Fewer patients reported fear of the unknown (58% versus 44%) and distress over believing something could have been done to prevent disease progression (26% versus 12%), but more patients reported hope of keeping the disease stable (46% versus 59%) and confidence in treatment options (29% versus 37%). During their treatment journey, more women with children ≤17 years old were distressed because they believed something could have been done to prevent disease progression versus women with children 18+ years old or no children. There were instances of misalignment between patient expectations and what oncologists actually discussed with patients. Our findings suggest that patients exhibit an ability to adapt during their disease. Having a shared understanding of concerns and needs of patients serves to strengthen the patient-oncologist alliance and creates a framework for oncologists to tailor disease management and coping strategies to improve quality of life for patients of all ages with MBC. [ABSTRACT FROM AUTHOR]

Background. Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS. Methods. We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan–Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model. Results. The presence of metastases (3y-EFS: 0.33 vs. 0.68; P < 0.001 ; HR = 3.4, 95% CI 1.7 to 6.6; 3y-OS: 0.48 vs. 0.85; P < 0.001 ; HR = 4.23, 95% CI 1.8 to 9.7), large tumor volume (≥200 ml) (3y-EFS: 0.36 vs. 0.69; P = 0.02 ; HR = 2.1, 95% CI 1.1 to 4.0; 3y-OS: 0.42 vs. 0.73; P = 0.04 ; HR = 2.1, 95% CI 1.03 to 4.5), and age ≥18 years (3y-EFS: 0.41 vs. 0.60; P = 0.02 ; HR = 2.6, 95% CI 1.3 to 5.2; 3y-OS: 0.294 vs. 0.59; P = 0.01 ; HR = 2.92, 95% CI 1.29 to 6.6) were revealed as adverse prognostic factors. Conclusion. Young age seems to positively influence patients' survival, especially in patients with primary metastatic disease. In this context, our results support other studies, stating that older age has a negative impact on survival. Tumor volume, metastases, and the type of local therapy modality have an impact on the outcome of sacral EwS. Level of evidence: Level 2. This trial is registered with NCT00020566 and NCT00987636. [ABSTRACT FROM AUTHOR]

Periocular tumors are common in infancy. The most common periocular tumors are capillary hemangiomas, which are present in 1-2% of newborns and develop in 10%-12% of children by the age of 1 year old. Deep capillary hemangiomas may be more challenging to diagnose than superficial capillary hemangiomas and can be confused with other orbital lesions. Deep orbital hemangiomas can mimic teratoma, lymphangioma, rhabdomyosarcoma, metastatic neuroblastoma, and granulocytic sarcoma. In this paper, we describe 2 pediatric cases where previously diagnosed dermoid cyst and dacrocystocele were found to be capillary hemangiomas upon biopsy. Approaches to distinguish capillary hemangiomas fromother periocular tumors are further discussed. To our knowledge, this is the first case report of periocular hemangiomas imitating a dermoid cyst and a dacrocystocele. These cases emphasize the importance of including infantile hemangiomas in the differential diagnosis of subcutaneous periocular abnormalities. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common malignant diseases occurring in women, and its incidence increases over the years. It is the main site of origin in ocular metastatic disease in women, and, due to its hematogenous nature of metastatic spread, it affects mainly the uveal tissue. The purpose of this paper is to summarize the clinical manifestations of the breast cancer ocular metastatic disease, alongside the side effects of the available treatment options for the management and regression of the systematic and ophthalmic disease. [ABSTRACT FROM AUTHOR]

Phosphatidylinositol 3,4,5-trisphosphate- (PIP3-) dependent Rac exchanger 1 (P-Rex1) functions as Rho guanine nucleotide exchange factor and is activated by synergistic activity of Gβγ and PIP3 of the heterotrimeric G protein. P-Rex1 activates Rac GTPases for regulating cell invasion and migration and promotes metastasis in several human cancers including breast, prostate, and skin cancer. The protein is a promising therapeutic target because of its multifunction roles in human cancers. Herein, the present study attempts to identify selective P-Rex1 natural inhibitors by targeting PIP3-binding pocket using large-size multiple natural molecule libraries. Each library was filtered subsequently in FAF-Drugs4 based on Lipinski's rule of five (RO5), toxicity, and filter pan assay interference compounds (PAINS). The output hits were virtually screened at the PIP3-binding pocket through PyRx AutoDock Vina and cross-checked by GOLD. The best binders at the PIP3-binding pocket were prioritized using a comparative analysis of the docking scores. Top-ranked two compounds with high GOLD fitness score (>80) and lowest AutoDock binding energy (< -12.7 kcal/mol) were complexed and deciphered for molecular dynamics along with control-P-Rex1 complex to validate compound binding conformation and disclosed binding interaction pattern. Both the systems were seen in good equilibrium, and along the simulation time, the compounds are in strong contact with the P-Rex1 PIP3-binding site. Hydrogen bonding analysis towards simulation end identified the formation of 16 and 22 short- and long-distance hydrogen bonds with different percent of occupancy to the PIP3 residues for compound I and compound 2, respectively. Radial distribution function (RDF) analysis of the key hydrogen bonds between the compound and the PIP3 residues demonstrated a strong affinity of the compounds to the mentioned PIP3 pocket. Additionally, MMGB/PBSA energies were performed that confirmed the dominance of Van der Waals energy in complex formation along with favorable contribution from hydrogen bonding. These findings were also cross-validated by a more robust WaterSwap binding energy predictor, and the results are in good agreement with a strong binding affinity of the compounds for the protein. Lastly, the key contribution of residues in interaction with the compounds was understood by binding free energy decomposition and alanine scanning methods. In short, the results of this study suggest that P-Rex1 is a good druggable target to suppress cancer metastasis; therefore, the screened druglike molecules of this study need in vitro and in vivo anti-P-Rex1 validation and may serve as potent leads to fight cancer. [ABSTRACT FROM AUTHOR]

What is known and objective Sunitinib, a CYP3A4 substrate, is standard of care treatment in metastatic renal cell carcinoma ( mRCC) and is administered orally as a single dose of 50 mg, in a 4 weeks on/2 weeks off regimen. Frequently, dose reduction is necessary because of toxicity, as is the association of comedication to treat side effects. In addition, existing comorbidities in these patients necessitate the intake of various classes of chronic medication. Only limited data are available on the risk of drug-drug interactions ( DDI). The objective of our paper was to evaluate prescribed dose, comedication, risk of drug-drug interactions and outcome among patients with mRCC treated with sunitinib. Methods A single-centre, retrospective analysis was performed for patients with mRCC treated with sunitinib. The drug interaction databases 'Clinical Pharmacology'© and 'Lexicomp'© were used to screen for possible interactions. Results and discussion The hospital files of 36 patients with mRCC were evaluated. Twenty-two patients received sunitinib as first-line treatment. Progression-free survival ( PFS) in this first-line group was longer for patients that started with full-dose sunitinib (21·1 months; n = 12) than for patients started on reduced dose (3·5 months; n = 10). In the whole group of 36 patients, an average of 6·8 comedications was taken. Possible pharmacodynamic drug-drug interactions were most frequently found (47%) and reported as major interactions ( QT prolongation). Risk of pharmacokinetic interactions due to co-administration of CYP inhibitors, CYP inducers, CYP substrates and PgP substrates was reported for 8%, 11%, 53% and 19%, respectively. These interactions were reported as major or moderate. What is new and conclusion Patients with mRCC under treatment with sunitinib at a reduced starting dose had a decreased PFS compared with patients started with full-dose sunitinib. Due to adverse drug reactions and comorbidity, patients under sunitinib, a CYP3A4 substrate, took an average of 6·8 comedications provoking an important risk of major-to-moderate drug-drug interactions. With the help of a multidisciplinary team, avoidance of drug-drug interactions could be obtained. Moreover, serial ECG monitoring is recommended for patients at high risk of QT prolongation. [ABSTRACT FROM AUTHOR]

Ectopic breast tissue has the ability to undergo all the pathological changes of the normal breast, including breast cancer. Gastrointestinal metastasis of breast cancer is rarely observed and it is very difficult to differentiate gastric metastases from primary gastric cancer. We present a case of 52-year-old female, who suffered from abdominal pain. Physical examination showed a palpable mass in the left anterior axilla and computerized tomography revealed gastric wall thickening with linitis plastica. When gastroscopic biopsy showed no signs of malignancy, excisional biopsy was performed in the left axilla. Histological examination revealed invasive lobular carcinoma of the breast, consistent with ectopic breast cancer. Further gastroscopic submucosal biopsies and immunohistochemical studies revealed gastric metastases of invasive lobular carcinoma. Axillary ectopic breast tissue carcinomas can mimic axillary lymphadenopathies. Additionally, gastric metastasis of breast cancer is an uncommon but possible condition. To the best of our knowledge, this is the first report of ectopic breast cancer with gastric metastasis. [ABSTRACT FROM AUTHOR]

The aim of the paper is to evaluate the efficacy of Cyber Knife® for the treatment of primary or metastatic retroperitoneal tumours. Twenty-eight patients were treated. The prescription isodose line (median, 78%; range, 70-84%) covered the planning target volume at a total dose of 2000-6000 cGy (median, 4500 cGy) and a biologically effective dose of 3750-10 080 cGy (median, 7680 cGy) in 2-10 fractions (median, five fractions). The results showed that the complete response, partial response, stable disease, and progressive disease rates were 43% (12/28), 36% (10/28), 18% (5/28), and 4% (1/28) respectively. The overall response rate was 96%. The 1-, 2- and 3-year local control rates were 92%, 86%, and 86% respectively. The 1-, 2- and 3-year overall survival rates were 60%, 49%, and 49% respectively. No significant difference was found between local progression-free survival and overall survival. Moreover, if a patient only had metastases in the retroperitoneum and local control was effective, there was no significant difference between local progression-free survival and overall progression-free survival. In conclusion, Cyber Knife treatment for retroperitoneal tumours resulted in high response rates with minimal side effects. All radiation-induced side effects were well tolerated. [ABSTRACT FROM AUTHOR]

Despite diagnostic advances, breast cancer remains the most prevalent cancer among women in the United States. The armamentarium of treatment options for metastatic disease is limited and mostly ineffective with regards to eradicating cancer. However, there have been novel findings in the recent literature that substantiate the function of the microenvironment in breast cancer progression and the support of metastasis to tertiary sites such as bone marrow. The uncovered significance of the microenvironment in the pathophysiology of breast cancer metastasis has served to challenge previously widespread theories and introduce new perspectives for the future research to eradicate breast cancer. This paper delineates the current understanding of the molecular mechanisms involved in the interactions between breast cancer cells and the microenvironment in progression, metastasis, and dormancy. The information, in addition to other mechanisms described in bone marrow, is discussed in the paper. [ABSTRACT FROM AUTHOR]

Although advances in cytotoxic treatments have been obtained in several neoplasias, in metastatic melanoma there was no drug able to significantly change the natural history of the disease in the last 30 years. In the last decade, translational research identified important mechanisms in malignant transformation, invasion, and progression. Signaling pathways can be abnormally activated by oncogenes. The identification of oncogenic mutated kinases implicated in this process provides an opportunity for new target therapies. The melanoma dependence on BRAF-mutated kinase allowed the development of inhibitors that produced major responses in clinical trials. This is the beginning of a novel class of drugs in metastatic melanoma; the identification of the transduction signaling networking and other "druggable" kinases is in active research. In this paper, we discuss the ongoing research on cellular signaling inhibition, resistance mechanisms, and strategies to overcome treatment failure. [ABSTRACT FROM AUTHOR]

Purpose. Patients with high-risk prostate cancer (PC) can be treated with high-dose intensity-modulated radiotherapy (IMRT) and long-term androgen deprivation (AD). In this paper we report on (i) late toxicity and (ii) biochemical (bRFS) and clinical relapse-free survival (cRFS) of this combined treatment. Methods. 126 patients with high-risk PC (T3-4 or PSA > 20 ng/mL or Gleason 8-10) and =24 months of followup were treated with high-dose IMRT and AD. Late toxicity was recorded. Biochemical relapse was defined as PSA nadir +2 ng/mL. Clinical relapse was defined as local failure or metastases. Results. The incidence of late grade 3 gastrointestinal and genitourinary toxicity was 2 and 6%, respectively. Five-year bRFS and cRFS were 73% and 86% respectively. AD was a significant predictor of bRFS (P = 0.001) and cRFS (P = 0.01). Conclusion. High-dose IMRT and AD for high-risk PC offers excellent biochemical and clinical control with low toxicity. [ABSTRACT FROM AUTHOR]

Improvement of quality of life and survival of cancer patients will be greatly enhanced by the development of highly effective drugs to selectively kill malignant cells. Artemisinin and its analogs are naturally occurring antimalarials which have shown potent anticancer activity. In primary cancer cultures and cell lines, their antitumor actions were by inhibiting cancer proliferation, metastasis, and angiogenesis. In xenograft models, exposure to artemisinins substantially reduces tumor volume and progression. However, the rationale for the use of artemisinins in anticancer therapy must be addressed by a greater understanding of the underlying mechanisms involved in their cytotoxic effects. The primary targets for artemisinin and the chemical base for its preferential effects on heterologous tumor cells need yet to be elucidated. The aim of this paper is to provide an overview of the recent advances and new development of this class of drugs as potential anticancer agents. [ABSTRACT FROM AUTHOR]

The potent antiangiogenic pigment epithelium-derived factor (PEDF) has shown promise against osteosarcoma, a tumour that originates in the bone and metastasises to the lungs. Neurotrophic, antiangiogenic, antiproliferative, and antimetastatic properties of PEDF have been attributed to a number of functional epitopes on the PEDF glycoprotein. StVOrth-2 (residues 78-102) and StVOrth-3 (residues 90-114) are two PEDF-derived peptides based on these functional epitopes. StVOrth-2 has previously been shown to inhibit osteosarcoma cell proliferation, while StVOrth-3 increased osteosarcoma cell adhesion to collagen I in vitro. In this paper, we have evaluated systemically and continuously delivered StVOrth-2 and StVOrth-3 using a clinically relevant murine model of osteosarcoma with spontaneous metastasis. Treatment with StVOrth-2 or StVOrth-3 with microosmotic pumps was initiated after primary osteosarcoma was established in the tibia. While treatment with StVOrth-2 and StVOrth-3 did not appear to affect local tumour invasion, tumour necrosis or apoptosis, StVOrth-2 predominantly restricted the growth of primary tumours, while StVOrth-3 restricted the burden of pulmonary metastatic disease. No peptide caused gross toxicity in mouse tissues as assessed by measuring weight of animals, serum biochemistry, and gross tissue observation. The differential effects exhibited by StVOrth-2 and StVOrth-3 in this orthotopic model of osteosarcoma may be related to the functional epitopes on the PEDF glycoprotein that they represent. [ABSTRACT FROM AUTHOR]

Non-small-cell lung cancer (NSCLC) is a heterogeneous disease due to the presence of different clinically relevant molecular subtypes. Until today, several biological events have been identified in lung adenocarcinoma, including epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations, offering new hopes to patients with metastatic disease. Unfortunately, in approximately 50% of adenocarcinoma and for those harbouring K-RAS mutations, the most frequent mutation in Caucasian lung adenocarcinoma, so far no specific drug demonstrated efficacy. The rat sarcoma (RAS) genes, including H-RAS, K-RAS, and N-RAS, encode a family of proteins regulating cell growth, differentiation, and apoptosis. K-RAS mutations are present in 20-30% of NSCLC and occur most commonly, but not exclusively, in adenocarcinoma histology and life-long smokers. Although in colorectal cancer patients K-RAS mutations represent a validated negative predictive biomarker for treatment with anti-EGFRmonoclonal antibodies, their role in selecting specific treatment for NSCLC patients remains undefined. Aim of the present paper is to critically analyze the prognostic and predictive value of K-RAS mutations in NSCLC. [ABSTRACT FROM AUTHOR]

The transforming growth factor-beta (TGFβ) superfamily encompasses widespread and evolutionarily conserved polypeptide growth factors that regulate and orchestrate growth and differentiation in all cell types and tissues. While they regulate asymmetric cell division and cell fate determination during early development and embryogenesis, TGFβ family members play a major regulatory role in hormonal and immune responses, cell growth, cell death and cell immortalization, bone formation, tissue remodeling and repair, and erythropoiesis throughout adult life. The biological and physiological functions of TGFβ, the founding member of this family, and its receptors are of central importance to human diseases, particularly cancer. By regulating cell growth, death, and immortalization, TGFβ signaling pathways exert tumor suppressor effects in normal cells and early carcinomas. Thus, it is not surprising that a high number of human tumors arise due to mutations or deletions in the genes coding for the various TGFβ signaling components. As tumors develop and progress, these protective and cytostatic effects of TGFβ are often lost. TGFβ signaling then switches to promote cancer progression, invasion, and tumor metastasis. The molecular mechanisms underlying this dual role of TGFβ in human cancer will be discussed in depth in this paper, and it will highlight the challenge and importance of developing novel therapeutic strategies specifically aimed at blocking the prometastatic arm of the TGFβ signaling pathway without affecting its tumor suppressive effects. [ABSTRACT FROM AUTHOR]

The HGF/MET signaling pathway is abnormal in numerous cancers including ovarian cancer. MET is expressed in 70% of human cancer and it is overexpressed in 30% of ovarian cases and cancer cell lines. The HGF/MET pathway plays a role in the initiation and progression of ovarian cancer through the most distinctive biologic program known as "invasive growth" which is accomplished through a coordinated activation of cell motility, invasiveness, degradation of extracellular matrix, survival, and proliferation. Because of its ubiquitous role in cancer, the MET axis seems to be an attractive target for cancer therapy. Numerous HGF/MET pathway inhibitor compounds are already in use in clinical trials in various solid tumors. In this paper, we will discuss the HGF/MET pathway in ovarian cancer, its clinical significance, and its potential use as a target therapy in the future. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound (EUS) is the most sensitive imaging modality for solid pancreatic lesions. The specificity, however, is low (about 75%). It can be increased to 100% with an accuracy of 95% by the addition of fine-needle aspiration (FNA). Cytopathology plays an important role. The final diagnosis is based upon the correlation of clinical, EUS, and cytologic features. A close interaction with the cytopathologist is required in improving the diagnostic yield. In this paper, we present an overview of the role of EUSguided FNA and importance of close interaction with the cytopathologist. Day to day examples of different solid pancreatic lesions have been presented at the end. [ABSTRACT FROM AUTHOR]

Although small bowel intussusception is one of the most common abdominal emergencies in childhood, it is rare in adults and usually occurs as a result of an underlying pathology. Sarcomatoid carcinoma, a very rare subtype of lung cancer, rarelymetastasizes to small bowel and causes complications. In this paper, we aim to describe a patient with small bowel intussusception caused by an isolated small bowel metastasis of the sarcomatoid carcinoma of the lung by reviewing the literature. [ABSTRACT FROM AUTHOR]

This paper describes the case of a 25-year-old woman with virilisation occurring during pregnancy in the presence of metastatic colorectal cancer. Virilisation during pregnancy is rare. The potential causes include adrenal, foetal, or ovarian pathologies. The most common causes during pregnancy are pregnancy luteoma and hyperreactio luteinalis. The incidence of cancer during pregnancy is rare and the incidence of colorectal cancer (CRC) in pregnancy is even rarer. The presenting signs and symptoms of CRC can be confused with symptoms commonly encountered during pregnancy, thereby delaying diagnosis and commencement of treatment. Diagnosis and staging also proves more problematic in the pregnant patient as the usual modalities of colonoscopy with biopsy and imaging with CT are relatively contraindicated. Treatment is dependent on gestational age of the foetus. There is currently no agreed best practice as to the role of prophylactic oophorectomy in the prevention of metachronous ovarian metastases. Surgical and adjuvant treatments have implications for females of child-bearing age. [ABSTRACT FROM AUTHOR]

Over the past decade, irinotecan has become one of the first-line chemotherapeutic agents used in the treatment of metastatic colorectal cancer. Recently, irinotecan has been administered transarterially in order to perform chemoembolization in the liver. In the limited number of reports available to date using this approach, serious adverse effects have not yet been reported. In this paper, we describe the formation of an intercostal artery pseudoaneurysm after transarterial chemoembolization with irinotecaneluting beads in a patient with spinal metastasis from colorectal cancer. [ABSTRACT FROM AUTHOR]

Differentiated thyroid carcinoma (papillary and follicular) has a favorable prognosis with an 85% 10-year survival. The patients that recur often require surgery and further radioactive iodine to render them disease-free. Five percent of thyroid cancer patients, however, will eventually succumb to their disease. Metastatic thyroid cancer is treated with radioactive iodine if the metastases are radioiodine avid. Cytotoxic chemotherapies for advanced or metastatic noniodine avid thyroid cancers show no prolonged responses and in general have fallen out of favor. Novel targeted therapies have recently been discovered that have given rise to clinical trials for thyroid cancer. Newer aberrations in molecular pathways and oncogenic mutations in thyroid cancer together with the role of angiogenesis in tumor growth have been central to these discoveries. This paper will focus on themanagement and treatment of metastatic differentiated thyroid cancers that do not take up radioactive iodine. [ABSTRACT FROM AUTHOR]

Thyroid carcinoma showing squamous differentiation throughout the entire lesion is diagnosed as squamous cell carcinoma of the thyroid (SCCT) in the WHO classification. This entity is a rare disease and shows a dire prognosis; however, squamous differentiation ismore frequently detected in only a portion of papillary thyroid carcinoma. In this paper, we present our experience of 10 patients (8 primary lesions and 2 with recurrence in the lymph nodes) with papillary thyroid carcinoma having an SCC component (PTC-SCC). Only 3 of 8 primary lesions (38%) and none of the 2 recurrent nodes were preoperatively diagnosed as or suspected of having SCC components. All 10 patients underwent locally curative surgery. To date, 3 patients have died of carcinoma, and 2 had distant metastasis at diagnosis or had an undifferentiated carcinoma component. The other 7 are currently alive 5 to 43 months after diagnosis. Systemic adjuvant therapy after the detection of recurrence was effective for 2 patients. It is possible that some PTC-SCC patients without distant metastasis who undergo locally curative surgery can survive for a prolonged period and adjuvant therapies can be effective for local and distant recurrences. [ABSTRACT FROM AUTHOR]

Quality of life has become increasingly more important for men diagnosed with prostate cancer. In light of this and the recognized risks of androgen deprivation therapy (ADT), the guidelines and use of ADT have changed significantly over the last few years. This paper reviews the current recommendations and the future perspectives regarding ADT. The benefits of ADT are evident neoadjuvantly and adjuvantly in patients treated with external beam radiation therapy for intermediate- and high-risk disease, in patients who have undergone prostatectomy with lymph node involvement, in high-risk patients after definitive therapy, and in patients who have developed progression or metastasis. Finally, this paper reviews the risks and benefits of each of these scenarios and the risks of androgen deprivation in general, and it delineates the areas where ADT was previously recommended, but where evidence is lacking for its additional benefit. [ABSTRACT FROM AUTHOR]

Background. Malignant melanoma incidence is increasing dramatically. We report herein a case of the rarest acral lentiginous type. Case Report. A 58-year-old man presented with a melanoma resembling lesion over the sole of his right foot, measuring 15-20mm in diameter. An excisional biopsy with a narrow (2mm) margin of surrounding skin was obtained. Histological findings were consistent with a diagnosis of acral lentiginous melanoma. Sentinel lymph node biopsy was also performed and micrometastases were not identified in frozen-section examination. According to the AJCC system, the tumor stage was IB (T2aN0M0). A wide local excision of the biopsy scar with a margin of 2 cm was performed. A split-thickness thick skin graft was used to reconstruct the excisional defect. During an 18-month followup, no local or distant recurrence has been observed. This paper aims to extract an updated rational approach to the management of this disease out of an enormous body of knowledge. [ABSTRACT FROM AUTHOR]

Although a rare entity, chondrosarcoma is the most common malignant tumor of the chest wall. Most patients present with an enlarging, painful anterior chest wall mass arising from the costochondrosternal junction. CT scan with intravenous contrast is the gold standard radiographic study for diagnosis and operative planning. Contrary to previous dictum, resection may be performed in an appropriate surgical candidate based on imaging characteristics or image-guided percutaneous biopsy results; incisional biopsy is rarely required. The keys to successful treatment are early recognition and radical excision with adequate margins, as chondrosarcoma is relatively resistant to radiotherapy and conventional cytotoxic chemotherapy. Overall survival is excellent in most surgical series from experienced centers. Complete excision with widely negative microscopic margins at the initial operation is of the utmost importance, as local recurrence portends systemic metastasis and eventual tumor-related mortality. This paper summarizes data from relevant surgical series and thereupon draws conclusions regarding preoperative, intraoperative, and postoperative management of thoracic chondrosarcoma. [ABSTRACT FROM AUTHOR]

Diagnosis and management of vertebral metastasis requires a systematic approach to patient identification as well as selection of appropriate therapy. Rapid identification and prompt intervention in the treatment of malignant epidural spinal cord compression (MESCC) is key to maintaining quality of life. This paper provides a series of tools as well as guidance in selecting effective and evidence-based therapy individualized to the specific patient. [ABSTRACT FROM AUTHOR]

WARREN M. (2010) European Journal of Cancer Care 19, 564–574 Uncertainty, lack of control and emotional functioning in women with metastatic breast cancer: a review and secondary analysis of the literature using the critical appraisal technique A diagnosis of metastatic (or secondary) breast cancer is frequently more distressing than the diagnosis of a primary tumour since it indicates that the cancer is no longer curable. Relatively little is known, however, about women's experiences of this condition in comparison with those diagnosed with primary breast cancer. This paper therefore reports findings from a secondary analysis of the published literature on the topic using tools from the critical appraisal skills programme to identify and analyse appropriate papers, and the constant comparative method as a means of identifying any overarching or dominant themes emerging from the literature. Uncertainty, lack of control and poor emotional functioning emerged as the main themes affecting women with metastatic breast cancer. These are discussed in relation to their antecedents in the original studies and their implications for nursing care. The themes demonstrate that living with metastatic (or secondary) breast cancer is a multifaceted experience that is influenced by a large number of factors, many of which are under-researched in comparison with those affecting women diagnosed with primary disease. It is clear, however, that women affected by the condition need a great deal more support than they currently receive, and new services may be required to meet these needs. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma is the most common kidney tumor in adults. Cutaneous metastasis is a rare first symptom of the disease. This paper describes the diagnosis of a renal cell carcinoma that was indicated by cutaneous metastasis in the head and neck region, and considers the etiopathogenesis of such cases. A careful skin examination is important to detect cutaneous metastasis associated with renal cell carcinomas.Metastatic skin lesions in the head and neck region must be taken into consideration during a differential diagnosis. [ABSTRACT FROM AUTHOR]

Cell adhesion and migration are key determinants in tumor metastasis. Adherence of tumor cell to the extracellular matrix is mediated via integrin containing focal adhesions (FAs). Binding of integrins to ECM triggers phosphorylation of two major components of FAs, focal adhesion kinase (FAK) and Src, activating downstream signaling pathway which leads to FA disassembly and cell migration. In this paper, we analyze how phosphorylation of FAK regulates its trafficking at FAs in living human astrocytoma cells. Upon pervanadate-induced FAK phosphorylation, phosphorylated FAK appeared highly expressed at newly formed membrane ruffles. This effect was abolished in presence of the specific Src inhibitor PP2. Our findings demonstrate that upon phosphorylation, FAK delocalizes from FAs to membrane ruffles. [ABSTRACT FROM AUTHOR]

Ovarian cancer affects approximately 25,000 women in the United States each year and remains one of the most lethal female malignancies. A standard approach to therapy is surgical cytoreduction, after which the remaining microscopic residual disease is treated with chemotherapy. The vast majority of patients have disease recurrence, underscoring the crucial need for approaches to control the regrowth, or colonization, of tissues after local treatment. Improved therapies require mechanistic information about the process of metastatic colonization, the final step in metastasis, in which cancer cells undergo progressive growth at secondary sites. Studies ofmetastasis suppressors are providing insights into events controlling metastatic colonization. This paper reviews our laboratory's approach to the identification, characterization, and functional testing of the JNKK1/MKK4 metastasis suppressor in ovarian cancer metastatic colonization. Specifically, we demonstrate that interaction of ovarian caner cells with the omentalmicroenvironment activates JNKK1/MKK4 resulting in decreased proliferation without affecting apoptosis. The potential role of the omental microenvironment, specifically milky spot structures, is also described. It is our goal to provide this work as a usable paradigm that will enable others to study metastasis suppressors in clinical and experimental ovarian cancer metastases. [ABSTRACT FROM AUTHOR]

Background. This paper aimed to assess the utility of second-line chemotherapy in patients with advanced soft-tissue sarcoma. Materials and Methods. A retrospective search of a prospectively maintained database identified patients treated between 1991 and 2005. Patients with gastrointestinal stromal tumours, small round cell tumours, and Ewing's sarcoma were excluded. Response was assessed using WHO and RECIST. Patients who achieved stable disease for 6 months or more were classified as having disease control. Results. Three hundred and seventy-nine patients received second-line chemotherapy. Eighty-six (22.7%) achieved disease control. Median duration of response was 11 months (95% CI: 9-13). On multivariate analysis, pathological subtype, absence of lung metastases, and the use of combination chemotherapy were independent predictors of disease control. Twenty-eight (16.1%) patients who failed to respond to first-line therapy achieved disease control. Eight (2.1%) patients had sufficient downstaging to enable complete surgical resection. Progression-free survival was 23% at 6 months. Median overall survival was 8 months (95% CI: 7-10 months). On multivariate analysis, synovial histology and absence of lung metastases were associated with improved survival. Conclusion. Second-line chemotherapy can provide clinical benefit in over 20% of soft-tissue sarcoma patients. [ABSTRACT FROM AUTHOR]