LEPR hypomethylation is significantly associated with gastric cancer in males.

BACKGROUND: Previous study has shown LEPR is a candidate gene of prediction and treatment of gastric cancer (GC). The purpose of this study was to test whether LEPR methylation could predict the risk of GC. MATERIALS AND METHODS: Tumor tissues and 5-cm adjacent non-tumor tissues from 117 newly diagnosed and untreated GC patients were collected for the current methylation study. LEPR methylation levels were determined by quantitative methylation specific PCR (qMSP), and the methylation level of LEPR was described by the percentage of methylated reference (PMR). RESULTS: Our results showed that LEPR methylation levels were significantly lower in tumor tissues than those in adjacent non-tumor tissues (median PMR: 36.64% vs. 50.29%, P = 1E-4). In addition, LEPR methylation levels were found to be significantly associated with platelet (r = -0.198, P = .037). Further subgroup analysis showed that the association of LEPR promoter hypomethylation with GC was specific to males (males: P = 7E-5; females: P = .500). Notably, significant hypomethylation of LEPR promoter was found only in GC patients without recurrence (P = .002) but not in GC patients with recurrence (P = .146). The AUC of LEPR hypomethylation for identification of GC risk was 0.649 with a sensitivity of 67.5% and a specificity of 63.2%. In addition, the AUC of LEPR hypomethylation in males was 0.685 with a sensitivity of 68.4% and a specificity of 69.6%. CONCLUSION: LEPR hypomethylation can be used to predict the risk of GC in males. And it might also have the potential to predict the recurrence in GC patients.

Combination of Sintilimab and Anlotinib for Metastatic Osteosarcoma: A Case Report.

Background: As one of the most common types of primary bone sarcomas in adolescents and young adults, osteosarcoma has a high probability of local invasion and distant metastasis with a poor prognosis. Case Presentation: Here, we report the case of a 34-year-old patient with advanced metastatic osteosarcoma. Considering the high expression of PD-L1 and the inability of the patient to tolerate chemotherapy, anti-PD-1 antibody (sintilimab 200 mg, q3w) and anti-angiogenesis drug (anlotinib 8 mg D1-14, q3w) were administered. The metastatic lesions were treated with local radiotherapy. The patient obtained an 11.7-month-sustained remission period, and he also enjoyed a better quality of life. Conclusion: This case demonstrates that sintilimab plus anlotinib may be a feasible treatment regimen for osteosarcoma patients.

Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death.

The major obstacle to successful treatment of gastric cancer is chemotherapy resistance. Our study was designed to investigate the role of phosphoinositide 3-kinase (PI3K)/Akt pathway in the development of chemoresistance in gastric cancer. In the present study, elevated Akt expression and Akt phosphorylation (Ser 473), as well as decreased PTEN expression were observed in 28 cases of gastric cancer tissues. Etoposide and doxorubicin stimulated Akt and PI3K activities in 2 gastric cancer cell lines (BGC-823 and SGC-7901), and the activities were concentration and time-dependent. Up-regulation of PTEN expression in BGC-823 cells by PEAK8-PTEN transient transfection obviously decreased the basal and anticancer drugs induced Akt activities, then sensitized BGC-823 cells to etoposide and doxorubicin. Pretreatment of BGC-823 and SGC-7901 cells with wortmannin, a PI3K inhibitor, attenuated cells's resistance to etoposide and doxorubicin. In addition, pretreatment of wortmannin blocked etoposide and doxorubicin induced IkappaB-alpha degradation, NFkappaB activation, phosphorylation of Akt, MDM-2 and forkhead transcription factors. Wortmannin pretreatment also promoted the accumulation of p27/Kip, but inhibited the Mcl-1 expression. Furthermore, wortmannin promoted etoposide and doxorubicin induced caspase-3, caspase-9 activation and poly ADP-ribose polymerase cleavage. Taken together, the observations indicate the PI3K/Akt pathway plays an important role in the chemoresistance of gastric cancer cells. A new strategy for combined chemotherapy of gastric cancer should be designed to more specifically block PI3K/Akt pathway and then decrease the amount of resistant cells.

miR-136 targets MIEN1 and involves the metastasis of colon cancer by suppressing epithelial-to-mesenchymal transition.

MIEN1 is a novel oncogene, and it involves tumor progression in various cancer types, including colon cancer. However, the definite molecular mechanisms of MIEN1 in colon cancer progression remain to be completely elucidated. In the present study, bioinformatics prediction showed that miR-136 could be an upstream regulator of MIEN1; a luciferase assay and Western blot assay revealed that miR-136 negatively regulates MIEN1 expression via directly targeting its 3'-untranslated region sequence. Moreover, a functional assay using wound healing and transwell invasion showed that overexpressed miR-136 inhibited cell migration and invasion, and overexpression of MIEN1 partly rescued the above-mentioned effects of miR-136 in colon cancer cells. Additionally, a clinical sample assay showed that miR-136 expression was generally downregulated in colon cancer tissue, which was inversely correlated with MIEN1 expression. Furthermore, we found that miR-136 suppressed the Akt/NF-κB signaling pathway and epithelial-to-mesenchymal transition in colon cancer. These results suggest that miR-136, as a tumor suppressor, acts in tumor metastasis by suppressing MIEN1 expression in colon cancer, providing a novel target for the treatment of colon cancer.

Clinical significance of circulating tumor cells in squamous cell lung cancer patients.

BACKGROUND: Squamous cell carcinoma (SCC) of the lung represents 20-30% of non-small cell lung cancers (NSCLC) and is associated with a poor prognosis. OBJECTIVE: This study aims to investigate the presence of circulating tumor cells (CTCs) in squamous cell lung cancer patients and what its role might be in providing prognostic information. METHODS: Serial blood samples from 100 patients both before and after initiation of one cycle of standard chemotherapy were analyzed using CellSearch system. RESULTS: Of 105 patients enrolled, 100 were evaluable. ≥ 2 CTCs per 7.5 mL of blood were present in 29% of patients at baseline before chemotherapy, and 9% patients have more than 5 CTCs. Based on the current literature, the CTC measurements were dichotomized as 2-4 versus ≥ 5 CTCs. In the univariate analysis, CTC count ≥ 5 at baseline and CTC count ≥ 5 at both time points (before and after one cycle of chemotherapy) were significantly associated with a poor PFS and OS outcome. Both factors remained independent poor prognostic markers in the stepwise multivariate analysis. CONCLUSION: Our study indicate that the CTC count is a prognostic factor for PFS and OS outcomes in Chinese patients with locally advanced SCC of the lung.

Effect of glutamine-enriched nutritional support on intestinal mucosal barrier function, MMP-2, MMP-9 and immune function in patients with advanced gastric cancer during perioperative chemotherapy.

We studied the effects of glutamine-enriched nutritional support on intestinal mucosal barrier, matrix metalloproteinase (MMP)-2, MMP-9 and immune function during perioperative chemotherapy in patients with advanced gastric cancer. The study was conducted on 94 patients with advanced gastric cancer admitted from April 2015 to March 2016. They were randomly divided into observation and control groups, n=47. Control group was given basic nutritional support whereas glutamine-enriched nutritional support was given to patients in observation group. High-performance liquid chromatography was used to measure lactulose and mannitol ratio in urine (L/M) and ELISA was used to measure D-lactate levels before chemotherapy and in the 1st, 2nd and 3rd cycle of chemotherapy. Immunoglobulin level was detected by immune turbidimetry assay, T lymphocyte subsets were determined by flow cytometry after 3 cycles of chemotherapy, MMP-2 and MMP-9 of patients were compared between the two groups. The serious adverse reactions incidence (grade and IV) of patients were observed. To evaluate the life quality of patients, QLQ-C30 was used after 6 months. The levels of L/M and D-lactate in both groups after the first cycle of chemotherapy were significantly higher than that before chemotherapy; they began to decline after the second or third cycle, but were still significantly higher than the levels before chemotherapy (p<0.05). On comparison, between the two groups after 1st, 2nd, 3rd cycle after chemotherapy, L/M and D-lactate levels of patients in the observation group were significantly lower than in the control group (p<0.05). Incidence of serious adverse reactions (grades III and IV) in observation group was significantly lower than control group (p<0.05). At follow-up of 6 months, living quality scores of patients in observation group were significantly higher than control group (p<0.05). Glutamine-enriched nutritional support can effectively protect the intestinal mucosal barrier function in patients with advanced gastric cancer in their perioperative chemotherapy, improve the level of MMP-2 and MMP-9 in patients with advanced gastric cancer, enhance their immune function, reduce the incidence of adverse reactions and improve their quality of life, which is of remarkable clinical application value.

[Expression and clinical significance of kisspeptin-1, matrix metalloproteinase-2 and vascular endothelial growth factor in tissue of colon cancer].

OBJECTIVE: To detect the expression of kisspeptin-1 (KISS-1), matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in the tissue of colon cancer, and analyze the relativity between KISS-1, MMP-2, VEGF and pathological characteristics of colon cancer. METHODS: A total of 60 colon cancer patients and 60 patients with benign colorectal disease who received surgical treatment in our hospital from January 2009 to June 2010 were selected as observation group and control group respectively. The cancer tissue samples and excision samples collected from them were used to detect KISS-1, MMP-2 and VEGF with immunohistochemistry. RESULTS: The positive rates of KISS-1, MMP-2 and VEGF were 31.7%, 58.3% and 78.3% in observation group, and 73.3%, 16.7% and 33.3% in control group. The positive rate of KISS-1 in observation group was lower than that in control group (χ(2)=23.489, P<0.001), and the positive rates of MMP-2 and VEGF in observation group were higher than those in control group (χ(2)=27.469, P<0.001; χ(2)=25.817, P<0.001). The expressions of KISS-1, MMP-2 and VEGF were significantly related with the histological grade and TNM stage of colon cancer (χ(2)=8.997, P=0.011; χ(2)=6.163, P=0.013; χ(2)=8.519, P=0.014; χ(2)=9.160, P=0.002; χ(2)=16.577, P<0.001; χ(2)=10.523, P=0.001). CONCLUSION: It is helpful to understand the differentiation and clinical stage of colon cancer and provide evidence for clinical diagnosis and prognosis prediction by detecting KISS-1, MMP-2 and VEGF.

Current evidence on the four polymorphisms of VDR and breast cancer risk in Caucasian women.

There have been a few epidemiological studies reporting VDR polymorphisms including Fok1, Bsm1, Apa1 and Taq1with breast cancer incidence and therefore risk. The results however are controversial, often due to smaller sample size. Concerning most of the studies were performed on Caucasian women, we conducted this comprehensive meta-analysis encompassing 38,151 cases and 47,546 controls (Fok1: 13,152 cases, 17,443 controls; Bsm1: 14,755 cases, 18,633 controls; Apa1: 3080 cases, 3412 controls; Taq1: 7164 cases, 8068 controls) to better understand roles of the polymorphisms in breast cancer development among Caucasian population. We did not find any association of the most controversial genotype Fok1 with breast cancer risk in Caucasian women (ff vs. FF: OR = 1.05, 95% CI = 0.95-1.22, P = 0.32 for heterogeneity; ff vs. Ff: OR = 1.05, 95% CI = 0.94-1.17, P = 0.40; ff vs. Ff + FF: OR = 1.07, 95% CI = 0.95-1.14, P = 0.37 and ff + Ff vs. FF: OR = 1.04, 95% CI = 0.99-1.09, P = 0.23). For Bsm1, Apa1 and Taq1, no significant association was also not found in the homozygote comparison, heterozygote comparison, recessive and dominant models respectively. In conclusion, the current analysis suggested that the four polymorphisms (Fok1, Bsm1, Apa1 and Taq1) of VDR may be not associated with breast cancer risk in Caucasian women.