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The cancer burden in the oldest old has increased rapidly. This study aimed to investigate the epidemiology of second primary malignancy (SPM) in malignant solid tumor survivors aged 85 years and older utilizing the Surveillance, Epidemiology, and End Results (SEER) database. A total of 128,466 malignant solid tumor patients had been identified between 2000 and 2011, including 6774 patients who developed a SPM. The overall crude incidence of developing a SPM was 5.3%. Considering death as a competing event, the 3, 5, and 10-year cumulative incidence was 1.9%, 3.2%, and 5.4%, respectively. Relative younger age, male gender, surgery history, local stage and first primary malignancy (FPM) site located in the urinary system were related to higher cumulative incidence. A median time interval of 24.0 months was found between diagnosis of FPM and SPM. The most common SPM site was digestive system, whereas the least common was oral cavity and pharynx. The median overall survival (OS) was 49.0 months, and the median survival after SPM was 13.0 months. Relative older age, male gender and black race were associated with worse OS and survival after SPM, as well as higher hazard ratios of death. In conclusions, this study performed a comprehensive analysis of SPM among malignant solid tumor survivors aged 85 years and older. Additional studies are needed to characterize the specific cancer type of interest.

The role of bone morphogenetic protein 4 (BMP4), a crucial epithelial–mesenchymal transition (EMT) mediator, in the progression of hepatocellular carcinoma (HCC) patients heretofore has not been elucidated. The present study analyzed BMP4 expression in tumors and paired non-tumorous liver tissue and its correlation with clinicopathological characteristics from two independent cohorts consisting of 420 HCC patients. Functional analysis of BMP4 was performed in Bel-7402 and HCCLM3 HCC cells, and in a murine HCC model. The downstream targets of BMP4 in HCC were screened and confirmed. The results indicated that BMP4 expression was significantly increased in HCC tissue and highly metastatic HCC cells. BMP4 expression was correlated with vein invasion, overall survival and recurrence-free survival of HCC. BMP4 promoted HCC EMT and metastasis in vitro , and consistently in vivo . BMP4 knockdown blocked EMT and tumor metastasis in nude mice. ID2 was up-regulated by recombinant human BMP4, resulting in HCC EMT. Knockdown of ID2 blocked BMP4-induced EMT. In conclusion, BMP4 promotes invasion and metastasis of HCC by an induction of EMT via up-regulating ID2. BMP4 may be a valuable prognostic factor and potential therapeutic target for HCC therapy.

Background: Oxaliplatin (OXA) chemotherapy is widely used in the clinical treatment of colon cancer. However, chemo-resistance is still a barrier to effective chemotherapy in cases of colon cancer. Accumulated evidence suggests that the epithelial mesenchymal transition (EMT) may be a critical factor in chemo-sensitivity. The present study investigated the effects of Zinc finger E-box binding homeobox 1 (ZEB1) on OXA-sensitivity in colon cancer cells. Method: ZEB1expression and its correlation with clinicopathological characteristics were analyzed using tumor tissue from an independent cohort consisting of 118 colon cancer (CC) patients who receiving OXA-based chemotherapy. ZEB1 modulation of OXA-sensitivity in colon cancer cells was investigated in a OXA-resistant subline of HCT116/OXA cells and the parental colon cancer cell line: HCT116. A CCK8 assay was carried out to determine OXA-sensitivity. qRT-PCR, Western blot, Scratch wound healing and transwell assays were used to determine EMT phenotype of colon cells. ZEB1 knockdown using small interfering RNA (siRNA) was used to determine the ZEB1 contribution to OXA-sensitivity in vitro and in vivo (in a nude mice xenograft model). Result: ZEB1 expression was significantly increased in colon tumor tissue, and was correlated with lymph node metastasis and the depth of invasion. Compared with the parental colon cancer cells (HCT116), HCT116/OXA cells exhibited an EMT phenotype characterized by up-regulated expression of ZEB1, Vimentin, MMP2 and MMP9, but down-regulated expression of E-cadherin. Transfection of Si-ZEB1 into HCT116/OXA cells significantly reversed the EMT phenotype and enhanced OXA-sensitivity in vitro and in vivo. Conclusion: HCT116/OXA cells acquired an EMT phenotype. ZEB1 knockdown effectively restored OXA-sensitivity by reversing EMT. ZEB1 is a potential therapeutic target for the prevention of OXA-resistance in colon cancer.