Recent data support the role of S100A10 in tumorigenesis. In this study, we evaluated the value of S100A10 positivity as a possible biomarker in colorectal cancer. We evaluated S100A10 positivity by immunohistochemistry in a large population of colorectal cancer patients (n = 882). The relationships between S100A10 positivity and clinicopathological features and clinical outcome were analyzed. There were 36 % (319/882) tumors positive for S100A10 in all colorectal cancer samples. In contrast, normal colorectal epithelium was negative for S100A10 among all 562 specimens of adjacent normal mucosa. S100A10 positivity was correlated with poor differentiation (p = 0.0012) and disease stage (p = 0.003). S100A10 positivity was significantly correlated with shortened specific [log-rank p < 0.001; multivariate hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.09-2.04] and overall survival (log-rank p = 0.0012; multivariate HR, 1.34; 95% CI, 1.06-1.73). Knockdown of S100A10 by siRNA significantly reduced the proliferation, migration, and invasion capacity of colorectal cancer cell lines. Our results suggest a role for S100A10 as a prognostic marker and potential therapeutic target in colorectal cancer.

Epidermal growth factor (EGF) plays an important role in tumorigenesis. The association between the +61 A/G polymorphism of the EGF gene and colon cancer risk remains controversial and unclear. The objective of this study was to investigate the association between EGF +61 A/G polymorphism and colon cancer risk in a Chinese population. A hospital-based case-control study was conducted to assess the possible association between EGF +61 A/G polymorphism and colon cancer risk. A total of 180 colon cancer patients and 180 cancer-free healthy controls were recruited in the Chinese population. Genomic DNA was isolated from peripheral blood, and gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Colon cancer patients had a significantly higher frequency of +61 GG genotype (odds ratio [OR]=1.93, 95% confidence interval [CI]=1.07, 3.50; p=0.03) than that of controls. When stratified by the tumor location, tumor size, growth pattern, differentiation, and tumor-node-metastasis (TNM) stage of colon cancer, no statistically significant results were observed. Our study revealed that EGF +61 GG genotype was associated with a higher risk of colon cancer in Chinese population.

There is evidence that osteoarthritis (OA) is associated with ferroptosis which is a kind of lipid peroxidation-related cell death. Theaflavin-3,3 ′ -digallate(TF3), a polyphenol compound extracted from black tea, possesses antioxidative and anti-inflammatory properties, but its effects on chondrocyte ferroptosis in osteoarthritis (OA) remain unclear. Our present study aims at exploring the protective role and underlying mechanisms of TF3 against erastin-induced chondrocyte ferroptosis in OA. In human primary chondrocytes treated with erastin alone or combined with different doses of TF3, cell viability was assessed by MTS. Ferroptosis-related proteins, including Gpx4, HO-1, and FTH1, were detected by western blot. The levels of lipid peroxidation and Fe2+ were determined by fluorescence staining. Meanwhile, the change of related proteins in the Nrf2/Gpx4 signaling pathway was determined by western blot. siRNA-mediated Nrf2 knockdown and the Gpx4 inhibitor RSL3 were used to explore molecular mechanisms for TF3-induced ferroptosis in OA chondrocyte. The magnetic resonance imaging (MRI), HE staining, Masson’s staining, and immunohistochemistry were used to evaluate articular cartilage damages in the rat OA model. The results showed that Gpx4 expression was markedly downregulated in the chondrocytes of OA patients. TF3 reversed erastin-induced ferroptosis of human cultured chondrocytes, lipid ROS, and Fe2+ production in mitochondria. Moreover, the expression of Gpx4, HO-1, FTH1, and Nrf2 was markedly induced by TF3 in the erastin-treated chondrocytes. The antiferroptotic effect of TF3 was related to enhance Nrf2/Gpx4 signaling pathway. Finally, TF3 inhibited OA progression by alleviating in vivo cartilage damage related to chondrocyte ferroptosis. Thus, TF3 significantly inhibits chondrocyte ferroptosis by activating the Nrf2/Gpx4 signaling pathway, suggesting that TF3 serves as a potential therapeutic supplement for OA treatment.

4538 Background: Gastric cancer remains the 3rd leading cancer related death worldwide due to early disease recurrence. We hypothesize that hyperthermic intraperitoneal chemotherapy (HIPEC) may effectively prevent local regional recurrence for locally advanced gastric cancer patients who received curative intent surgery. Methods: Pathology proven gastric cancer patients with clinical T3/T4NxM0 disease are eligible for the study and will be randomized to either control group, who will receive standard radical gastrectomy and D2 lymph node dissection or HIPEC group, who will receive the same surgery and HIPEC with paclitaxel x 2 within the first week after surgery. All patients will receive either XELOX or SOX adjuvant chemotherapy. The primary end point is overall survival. Results: 648 patients from 16 high volume gastric medical centers were enrolled between May, 2015 and March, 2019. 331 and 317 patients were randomized to control and HIPEC groups respectively. The median follow-up time is 12.1 months. The common grade 3/4 toxicities ( > 5%) in control and HIPEC groups are anemia 6% vs. 4.1%, intraabdominal infection 5.4% vs. 3.8%, pneumonia 9.7% vs. 9.8%, fever 10.6% vs. 11.4% and hypoalbunemia 15.1% vs. 16.7% respectively. All three perioperative death (within 30 days after surgery) occurred in control group. One patient died from duodenum stump leak which led to multiple organ failure. One patient died from anastomotic led to intraabdominal infection and shock. The 3rd death was suicide caused by severe depression. At the time of this report, the number of event has not reached for final efficacy analysis. Conclusions: It is safe to administer HIPEC to patients received radical gastrectomy with D2 lymph node dissection within one week of surgery. The primary analysis will be expected in one year. Clinical trial information: NCT02356276 .

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