Mountain of studies has showed that right‐sided colon cancer (RSCC) and left‐sided colon cancer (LSCC) have different clinical presentation and biologic features and should be considered as two distinct disease entities. The survival difference between RSCC and LSCC remains controversial. Using Surveillance, Epidemiology, and End Results (SEER) database, we identified colon adenocarcinoma patients from 2004 to 2013. The 5‐year cause‐specific survival (CSS) was our primary endpoint. All statistical analyses were performed using the Intercooled Stata 13.0. All statistical tests were two‐sided. The study included 95,847 (58.72%) RSCC and 67,385 (41.28%) LSCC patients. RSCC patients were older, more often females, more Caucasian, more unmarried, more advanced T and N stage, larger tumor sizes, and more poorly differentiated tumor, while LSCC patients had more stage IV diseases. Location was an independent prognostic factor in the multivariable analysis. Compared with RSCC patients, the hazard ratio for LSCC was 0.87, 95% CI: 0.85–0.89 P < 0.001. There was no survival difference between RSCC and LSCC in the following situations: older than 68 years old, T3–4, N0, poorly differentiated, and undifferentiated diseases. We firstly reported that RSCC patients had a better prognosis than LSCC in mucinous adenocarcinoma/signet ring cell carcinoma patients. RSCC patients also had a better prognosis than LSCC in stage II disease. There is a need for further subdivisions when analyzing the survival difference between RSCC and LSCC patients. RSCC had lower mortality rate than LSCC in stage II disease and mucinous adenocarcinoma/signet ring cell carcinoma patients.
BackgroundOvarian cancer is a deadly disease. Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are frequently dysregulated in ovarian cancer. Overexpression of IAPs proteins has been correlated with tumorigenesis, treatment resistance and poor prognosis. Reinstalling functional cell death machinery by pharmacological inhibition of IAPs proteins may represent an attractive therapeutic strategy for treatment of ovarian cancer.MethodsCCK-8 and colony formation assay was performed to examine cytotoxic activity. Apoptosis was analyzed by fluorescence microscopy, flow cytometry and TUNEL assay. Elisa assay was used to determine TNFα protein. Caspase activity assay was used for caspase activation evaluation. Immunoprecipitation and siRNA interference were carried out for functional analysis. Western blotting analysis were carried out to test protein expression. Ovarian cancer cell xenograft nude mice model was used for in vivo efficacy evaluation.ResultsAPG-1387 demonstrated potent inhibitory effect on ovarian cancer cell growth and clonogenic cell survival. APG-1387 induced RIP1- and TNFα-dependent apoptotic cell death in ovarian cancer through downregulation of IAPs proteins and induction of caspase-8/FADD/RIP1 complex, which drives caspase-8 activation. NF-κB signaling pathway was activated upon APG-1387 treatment and RIP1 contributed to NF-κB activation. APG-1387 induced cytoprotective autophagy while triggering apoptosis in ovarian cancer cells and inhibition of autophagy enhanced APG-1387-induced apoptotic cell death. APG-1387 exhibited potent antitumor activity against established human ovarian cancer xenografts.ConclusionsOur results demonstrate that APG-1387 targets IAPs proteins to potently elicit apoptotic cell death in vitro and in vivo, and provide mechanistic and applicable rationale for future clinical evaluation of APG-1387 in ovarian cancer.
Background: Renal cell carcinoma (RCC) is the most common type of kidney tumor with increasing incidence. Tyrosine Kinase Inhibitors (TKIs) are considered important treatment in the management of metastatic RCC. Some previous studies demonstrated that sorafenib treatment is associated with a significantly increased risk of potentially life-threatening adverse events, like bleeding. But bleeding at the fundus site is the rarest type of hemorrhage. As for TKIs' risk of bleeding, how we distinguish the degree of bleeding and what optimal strategies should we take to manage bleeding, needs to be studied systematically.Results: With a long-term exposure (17 months) to sorafenib, he experienced blurred vision in his right eye and was hospitalized. The patient's diagnosis was central retinal vein occlusion (CRVO) of the right eye. Unfortunately sorafenib was terminated.Materials and Methods: The authors describe the first case of unilateral fundus hemorrhage induced by sorafenib. A 42-year-old man was diagnosed metastatic left RCC, with clinical stage and prognostic risk being assessed as T4N1M1 and intermediate. He received a radical left nephrectomy and retroperitoneal lymph node dissection, with taking the oral multi-targeted TKI, sorafenib (800 mg daily) from 7 months to 7 days before the surgery and 7 days after the surgery restarting again until the occurrence of fundus hemorrhage.Conclusions: In this patient, long-term exposure to sorafenib possibly has increased the risk of fundus hemorrhage. This article provides us a previously undescribed morbidity associated with sorafenib, which reminds us of understanding the risk of bleeding and how this complication might be managed systematically.
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