BACKGROUND:It has been reported that antidiabetic drugs affect the risk of cancer and the prognosis of patients with diabetes, but few studies have demonstrated the influence of different antidiabetic agents on outcomes after anticancer therapy among patients with cancer. The objective of this study was to evaluate the influence of the antidiabetic drugs metformin and insulin on the prognosis of patients with advanced nonsmall cell lung cancer (NSCLC) plus type 2 diabetes who received first‐line chemotherapy.METHODS:Data on patients with NSCLC who had diabetes from 5 hospitals in China during January 2004 to March 2009 were reviewed retrospectively. Ninety‐nine patients were included in the final analysis. The influence of metformin and insulin on chemotherapy response rates and survival in these patients was evaluated.RESULTS:Chemotherapy with metformin (Group A) produced superior results compared with insulin (Group B) and compared with drugs other than metformin and insulin (Group C) in terms of both progression‐free survival (PFS) (8.4 months vs 4.7 months vs 6.4 months, respectively; P = .002) and overall survival (OS) (20.0 months vs 13.1 months vs 13.0 months, respectively; P = .007). Although no significant differences in the response rate (RR) were observed between these 3 groups, when groups B and C (ie, the nonmetformin group) were combined, there was a tendency for better disease control in Group A than that in nonmetformin group. No significant difference in survival was observed between chemotherapy with insulin (Group B) versus other drugs (Group C).CONCLUSIONS:The current data suggested that metformin may improve chemotherapy outcomes and survival for patients who have NSCLC with diabetes. Cancer 2011;. © 2011 American Cancer Society.

Our findings indicated that Chinese cancer patients and their families differed in their attitude toward truth telling and the attitudes toward such a disclosure were influenced by disease stage. Physicians should realize this phenomenon and pay more attention to the skills of how to disclose the cancer diagnosis.

GBM (glioblastoma multiforme) is the most common and aggressive brain tumor with no curative options available. Therefore, it is imperative to develop novel potent therapeutic drugs for GBM treatment. Here, we show that regorafenib, an oral multi-kinase inhibitor, exhibits superior therapeutic efficacy over temozolomide, the first-line chemotherapeutic agent for GBM treatment both in vitro and in vivo. Mechanistically, regorafenib directly stabilizes PSAT1 (phosphoserine aminotransferase 1), a critical enzyme for serine synthesis, to trigger PRKAA-dependent autophagy initiation and inhibit RAB11A-mediated autophagosomelysosome fusion, resulting in lethal autophagy arrest in GBM cells. Maintenance of PSAT1 at a high level is essential for regorafenib-induced GBM suppression. Together, our data provide novel mechanistic insights of regorafenib-induced autophagy arrest and suggest a new paradigm for effective treatment of GBM.

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Background and Aims Little is known about functions of microRNA (miR) passenger strands (miR*), or their roles in tumor development or progression. We screened for miRs and miR* whose levels were altered in metastatic colorectal cancer (CRC) cells and human tumor samples, and investigated their targets and effects on cell function and tumor progression in mice. Methods We performed array-based profile analysis to identify miRs whose levels were increased more than 2-fold in metastatic (SW620) CRC cells, compared with non-metastatic (SW480) cells. Quantitative PCR, immunoblot, and in situ hybridization analyses were used to measure miRNA levels in CRC cell lines and human tumor samples. We used miRNA duplex mimics or inhibitors to increase and decrease levels of miRNA in CRC cells, and assessed their activities and ability to form metastatic xenograft tumors in nude mice. Results Levels of miR-221* and miR-224 were reduced in metastatic, compared with non-metastatic, CRC cells; levels in human tumor samples correlated inversely with tumor stage and metastasis to lymph nodes, as well as patient survival times. SW480 cells transfected with miR-221* or miR-224 inhibitors had increased motility in vitro, compared with SW480 control cells, and formed larger, more metastatic tumors following into mice. SW620 cells transfected with miR-221* or miR-224 mimics had reduced migration and motility in vitro and formed smaller tumors with fewer metastases in mice, compared with control SW620 cells. We identified the 3'UTR of MBD2 mRNA as a target of miR-221* and 281 miR-224. MBD2 silences the gene encoding Maspin, a suppressor of metastasis. In CRC cells, we found that miR-221* and miR-224 increase the expression of Maspin through MBD2 downregulation. Conclusion In metastatic CRC cells, reduced levels of miR-221* and miR-224 increase levels of MBD2, thereby decreasing expression of the metastasis suppressor Maspin. Increased activities of miR-221* and miR-224 reduce growth and metastasis of CRC xenograft tumors in mice; these miRs might be developed as therapeutic reagents or biomarkers of CRC progression.

Colorectal cancer (CRC) is a major cause of cancer-related death worldwide. The poor prognosis of CRC is mainly due to uncontrolled tumor growth and distant metastases. In this study, we found that the level of FGF8 was elevated in the great majority of CRC cases and high FGF8 expression was significantly correlated with lymph nodes metastasis and worse overall survival. Functional studies showed that FGF8 can induce a more aggressive phenotype displaying epithelial-to-mesenchymal transition (EMT) and enhanced invasion and growth in CRC cells. Consistent with this, FGF8 can also promote tumor growth and metastasis in mouse models. Bioinformatics and pathological analysis suggested that YAP1 is a potential downstream target of FGF8 in CRC cells. Molecular validation demonstrated that FGF8 fully induced nuclear localization of YAP1 and enhanced transcriptional outcomes such as the expression of CTGF and CYR61, while decreasing YAP1 expression impeded FGF-8–induced cell growth, EMT, migration and invasion, revealing that YAP1 is required for FGF8-mediated CRC growth and metastasis. Taken together, these results demonstrate that FGF8 contributes to the proliferative and metastatic capacity of CRC cells and may represent a novel candidate for intervention in tumor growth and metastasis formation.

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Tumor cells evolve by interacting with the local microenvironment; however, the tumor-stroma interactions that govern tumor metastasis are poorly understood. In this study, proteomic analyses reveal that coculture with tumor-associated fibroblasts (TAF) induces significant overexpression of FGFR4, but not other FGFRs, in colorectal cancer cell lines. Mechanistic study shows that FGFR4 plays crucial roles in TAF-induced epithelial-to-mesenchymal transition (EMT) in colorectal cancer cell lines. Accumulated FGFR4 in cell membrane phosphorylates β-catenin, leading to translocation of β-catenin into the nucleus. Further, TAF-derived CCL2 and its downstream transcription factor, Ets-1, are prerequisites for TAF-induced FGFR4 upregulation. Furthermore, FGFR4-associated pathways are shown to be preferentially activated in colorectal tumor samples, and direct tumor metastasis in a mouse metastasis model. Our study shows a pivotal role of FGFR4 in tumor-stroma interactions during colorectal cancer metastasis, and suggests novel therapeutic opportunities for the treatment of colorectal cancer.