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Cutaneous melanoma represents around over 90% of all melanoma. With more effective treatments able to extend patients' survival, health‐related quality of life (HRQOL) is increasingly becoming an important endpoint in cancer clinical trials. They are often secondary outcomes measured in phase III randomized controlled trials and their implementation, collection, analysis, and reporting can be challenging methodologically. For these reasons, an increasing number of international recommendations introduced the standards regarding the conduct of HRQOL. In this systematic review, we appraise the adequacy of HRQOL reporting in phase III randomized controlled trials of stage III‐IV cutaneous melanoma and the clinical issues of immunotherapy and small‐molecular‐targeted therapy on HRQOL. Our search strategy totally got 55 articles, and only 13 studies met all inclusion criteria. Findings suggest that most treatments did not yield significant improvements in HRQOL but kept baseline levels, accompanied by prolonged survival and acceptable toxicity. Except for some existing limitations, reporting of HRQOL has made encouraging progress during the period covered by our search, but some aspects still need further optimization. [ABSTRACT FROM AUTHOR]

Abstract Background By using cDNA microarray analysis, we identified a G protein-coupled receptor, GPR39, that is significantly up-regulated in ESCC. The aim of this study is to investigate the role of GPR39 in human esophageal cancer development, and to examine the prevalence and clinical significance of GPR39 overexpression in ESCC. Methods The mRNA expression level of GPR39 was analyzed in 9 ESCC cell lines and 50 primary ESCC tumors using semi-quantitative RT-PCR. Immunohistochemistry was used to assess GPR39 protein expression in tissue arrays containing 300 primary ESCC cases. In vitro and in vivo studies were done to elucidate the tumorigenic role of GPR39 in ESCC cells. Results We found that GPR39 was frequently overexpressed in primary ESCCs in both mRNA level (27/50, 54%) and protein level (121/207, 58.5%), which was significantly associated with the lymph node metastasis and advanced TNM stage (P < 0.01). Functional studies showed that GPR39 has a strong tumorigenic ability. Introduction of GPR39 gene into ESCC cell line KYSE30 could promote cell proliferation, increase foci formation, colony formation in soft agar, and tumor formation in nude mice. The mechanism by which amplified GPR39 induces tumorigenesis was associated with its role in promoting G1/S transition via up-regulation of cyclin D1 and CDK6. Further study found GPR39 could enhance cell motility and invasiveness by inducing EMT and remodeling cytoskeleton. Moreover, depletion of endogenous GPR39 by siRNA could effectively decrease the oncogenicity of ESCC cells. Conclusions The present study suggests that GPR39 plays an important tumorigenic role in the development and progression of ESCC.

Metastasis accounts for 90% of cancer death worldwide, and effective therapeutic strategies are lacking. The aim of this work is to identify the key drivers in tumor metastasis and screen therapeutics for treatment of esophageal squamous cell carcinoma (ESCC). Gene Ontology analysis of The Cancer Genome Atlas (TCGA) gene expression datasets of ESCC patients with or without lympy metastasis identifies that TGFβ2 is highly enriched in the pathways essential for tumor metastasis and upregulates in the metastatic ESCC tumors. High TGFβ2 expression in ESCC correlates with metastasis and patient survival, and functionally contributes to tumor metastasis via activating extracellular signal‐regulated kinases (ERK) signaling. By screening of a library consisting of 429 bioactive compounds, imperatorin is verified as a novel TGFβ2 inhibitor, with robustly suppressive effect on tumor metastasis in multiple mice models. Mechanistically, direct binding of imperatorin and CREB1 inhibits phosphorylation, nuclear translocation of CREB1, and its interaction with TGFβ2 promoter, represses TGFβ2 expression and fibroblasts‐secreted CCL2, and then inactivates ERK signaling to block cancer invasion and abrogates the paracrine effects of fibroblasts on tumor angiogenesis and metastasis. Overall, the findings suggest the use of TGFβ2 as a diagnostic and prognostic biomarker and therapeutic target in ESCC, and supports the potential of imperatorin as a novel therapeutic strategy for cancer metastasis. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlation between ROBO2 and RASSF2A gene methylations and gastric cancer family history.Materials and Methods: ROBO2 and RASSF2A gene methylations in gastric cancer tissues and peri.cancerous tissues were detected with methylation.specific PCR in 36. patients with gastric cancer family history and 33 without gastric cancer family history. The correlations of ROBO2 and RASSF2A gene methylations with family history, and clinical and pathological characteristics were analyzed.Results: ROBO2 and RASSF2A gene methylations were all significantly higher in gastric cancer tissues (30% and 26%) than in peri-cancerous tissues (0% and 0%) (all P < 0.05). ROBO2 gene methylation was significantly lower in the patients with gastric cancer family history (17%, 6/36) than in the patients without gastric cancer family history (41%, 15/33) (P < 0.05).Conclusion: ROBO2 and RASSF2A gene methylations may be related to gastric tumorigenesis, and ROBO2 gene methylation is associated with sporadic gastric cancer. [ABSTRACT FROM AUTHOR]

Molecular-targeted therapy against tyrosine kinase receptors (RTKs) plays an important role in gastric cancer (GC) treatment. Understanding the correlation between RTK coexpression could better guide clinical drug use. In the present study, the coexpression status of c-MET, fibroblast growth factor receptor 2 (FGFR2), and human epidermal growth factor receptor 2 (HER2) in human GC and their clinical significance in clinical therapy were explored. Immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction and fluorescent in situ hybridization were performed in 143 cases of GC who had undergone gastrectomy without preoperative chemoradiotherapy. Their association with clinicopathological features and clinical prognosis was analyzed. The frequencies of c-MET, FGFR2, and HER2 overexpression were 47.6% (68/143), 34.3% (49/143), and 10.5% (15/143), respectively. In the RTK coexpression study, 30.1% of patients (43/143) were positive for only one RTK, 25.8% (37/143) were positive for two RTKs, 3.5% (5/143) had triple-positive status, and 40.6% (58/143) had triple-negative status. In survival analysis, the overexpression of c-MET, FGFR2, and HER2 were significantly associated with overall survival (OS) ( P =0.018, 0.004, and 0.049, respectively). In coexpression analysis, patients with triple-positive GC had the poorest OS ( P =0.013). In conclusion, RTK coexpression is significantly associated with poor clinical outcome in GC.

Aim: To explore the expression pattern of OCT4 in human esophageal squamous cell carcinoma and its significance in diagnosis and prognosis., Methods: Using real-time polymerase chain reaction (PCR), Western blotting, immunocytochemistry and immunohistochemistry, the expression of OCT4 in three esophageal squamous cancer cell lines, KYSE70, KYSE140 and KYSE450, was characterized. OCT4 expression was investigated in a series of 153 esophageal squamous cell carcinoma samples using immunohistochemistry and explored its association with clinicopathological features., Results: Immunohistochemically, OCT4 positive immunostaining was observed in cancer cell nuclei. OCT4 was variably expressed in three esophageal squamous cancer cell lines. Among 153 specimens, 105 (68.7%) were negative or weakly positive for OCT4 staining; 21 (13.7%) were moderately positive and 27 (17.6%) were strongly positive. Higher expression level of OCT4 was significantly associated with higher histological grade (P < 0.001) and poor clinic outcome (P < 0.001)., Conclusion: The expression of OCT4 enables the tumor to have a higher degree of stemness, which in turn results in a poorer clinical outcome for patients with esophageal squamous cell carcinoma.

Objective: To investigate the role of fascin, an actin bundling protein, in the development and progression of human esophageal squamous cell carcinoma (ESCC), and explore its association with the clinicopathologic characteristics and 5-year survival of the patients., Methods: Using tissue array and immunohistochemistry, the expression of fascin was determined in 241 ESCC tissues and the corresponding normal esophageal mucosal tissues., Results: ESCC tissues showed a significantly higher overexpression rate of fascin than the corresponding normal esophageal mucosal tissues (68.9% vs 15.5%, P<0.05). The overexpression of fascin was correlated to lymph node metastasis and TMN stage, but not to the patients' age, gender, tumor differentiation and general classification. Survival analysis showed that abnormal expression of fascin was associated with the 5-year survival rate of patients with ESCC., Conclusions: The abnormal expression of fascin may play an important role in the progression of ESCC, and detection of fascin expression may have important prognostic values.

Objective: To characterize the profile of chromosomal imbalances in esophageal cancer (EC) with or without family history in Linzhou, Henan Province of China., Methods: Comparative genomic hybridization (CGH) was used to examine 13 cases with positive family history of EC and 32 cases with negative family history of EC. RESULTS DNA copy number gains on chromosome 10q was observed only in the cases with postivie family history of EC (30%), and none in cases with a negative family history (P<0.05). DNA copy number losses on chromosome 15q were significantly higher in cases with postivie family history (38% vs 6%, P<0.05). The frequency of DNA copy number gains in 3q, 5p, 7p, 8q and DNA copy number losses in 3p, 19q, 9q were similar in the two groups (both beyond 20%) (P>0.05)., Conclusions: Frequent DNA copy number gains on chromosome 10q and losses on chromosome 15q in EC casers with postivie family history indicate that these chromosome sites may harbor the genes related to high susceptibility to EC. Such chromosomal sites as 3q, 5p, 7p, 8q, 3p, 19q, and 9q may contain important genes related with the environmental risk factors of esophageal carcinogenesis.