[Preliminary effects of toripalimab combined with axitinib in the treatment of advanced renal cell carcinoma].

Objective: To analyze the efficacy and safety of toripalimab combined with axitinib in the treatment of advanced renal cell carcinoma. Methods: Clinical data of 50 patients with advanced renal cell carcinoma who received axitinib combined with toripalimab were retrospectively collected from the database of Peking University Cancer Hospital. ORR, DCR, PFS, and OS were analyzed. Results: Among the 50 patients, 37 were males; median age was 56 (22-73) years; 38 were pathologically diagnosed as clear cell renal cell carcinoma and 12 were non-clear cell carcinoma. Common metastatic sites included lung, bone, lymph node, liver, and so on. 90% of the patients had received at least one-line of systemic therapy. With a median follow-up time of 11.9 months (0.8-24), 27 of the 50 patients are still on treatment, ORR was 34%, DCR was 86%, median PFS was 13.1 months (95%CI 5.8-20.4), and median OS has not yet reached. One-year OS rate was 84.6%. Common adverse reactions were proteinuria, diarrhea, hypertension, abnormal thyroid function, elevated transaminase, and hand-foot syndrome. Most adverse events were grade 1-2. Conclusion: Toripalimab combined with axitinib was efficient in the treatment of advanced renal cell carcinoma, and had manageable adverse reactions.

[Expression of Apelin and Snail protein in breast cancer and their prognostic significance].

Objective: To investigate the expression of Apelin and Snail proteins in breast cancer and their relationship with the clinicopathological features and prognosis. Methods: The expression of Apelin and Snail proteins was detected by immunohistochemistry in 89 cases of breast cancer and 50 cases of mammary adenosis collected from January to June in 2008 at Fujian Cancer Hospital; the expression was correlated with the clinicopathological features and outcome of the patients. Results: Apelin and Snail were expressed in 42 cases(47.2%)and 36 cases(40.4%)of breast cancers, respectively, and the expression was higher than that of control group (P<0.01). The expression of Apelin was positively correlated with Snail (r=0.230, P<0.05). Apelin expression was associated with lymph node metastasis and TNM staging(P<0.05). Snail expression was associated with lymph node metastasis(P<0.05). Kaplan-Meier survival curve showed that the prognosis of Apelin positive group was worse than that of Apelin negative group (P<0.01). There was no significant difference in prognosis between Snail negative and positive groups (P>0.05). The prognosis of Apelin and Snail in both positive groups was worse than that of Apelin and Snail both negative groups (P<0.01). Multivariate COX regression analysis showed that Apelin and TNM staging could be used as independent prognostic factors for breast cancer (P<0.05). Conclusions: Apelin and Snail are highly expressed in breast cancer, and associated with lymph node metastasis and TNM stage. There is a positive correlation between Apelin and Snail expression, which may suggest a role in breast carcinogenesis. The prognosis of breast cancer with expression of Apelin and co-expression of Apelin and Snail is poor. Therefore, Apelin may be used as an effective indicator to evaluate the prognosis of breast cancer patients.

Racial disparities in the association between diabetes mellitus-associated polymorphic locus rs4430796 of the HNF1ß gene and prostate cancer: a systematic review and meta-analysis.

Polymorphism 17q12 rs4430796 within HNF1ß is a genetic variant associated with both diabetes mellitus and prostate cancer, but findings on the correlations of rs4430796 with prostate cancer risk specifically are not in agreement, especially among diverse populations. To shed some light on the contradictory findings, therefore, we carried out a meta-analysis by pooling the odds ratios (ORs) with corresponding 95% confidence intervals (CIs) of all currently available case-control studies located within PubMed and Embase databases up to December 2012. A total of 16 studies comprising 30 datasets that collectively involved 25,535 prostate cancer patients and 25,726 controls were ultimately included in this analysis. The meta-analysis of all the studies revealed that the rs4430796 polymorphism was significantly associated with an increased risk of prostate cancer in all contrast models (ORA vs G = 1.25, 95%CI = 1.21-1.30, POR < 0.001; ORAA vs GG = 1.53, 95%CI = 1.45-1.62, POR < 0.001; ORAG vs GG = 1.24, 95%CI = 1.16-1.34, POR < 0.001; ORAA vs AG+GG = 1.36, 95%CI = 1.30-1.42, POR < 0.001; ORAA+AG vs GG = 1.37, 95%CI = 1.30-1.44, POR < 0.001). After subgroup analyses stratified by ethnicity, however, the rs4430796 polymorphism was significantly associated with prostate cancer in both Caucasians and Asians but not in African-Americans. In conclusion, our meta-analysis identified a significant association between the 17q12 rs4430796 polymorphism and prostate cancer risk, although the degree of this association and frequency of the causative allele varied among men of different races.

Histone modifications of Notch1 promoter affect lung CD4+ T cell differentiation in asthmatic rats.

Asthma is an inflammatory disease of the airways, and the current treatment in managing asthma is the control of inflammation. Notch signaling pathway has been linked to T-cell imbalance. The present study aimed to explore the histone modifications of Notch1 promoter in normal and asthmatic lung CD4+ T cells. Chromatin immunoprecipitation analysis showed that the acetylation levels of total H3, H4, site-specific H3K9, H3K14, H3K27, H3K18, H4K16, and the trimethylation levels of H3K4, H3K79 of Notch1 gene promoter were increased significantly in asthmatic lung CD4+ T cells compared to the control group, which correlated with increased P300, PCAF activity and decreased HDAC1, HDAC2 activity. After intervention of garcinol, a potent inhibitor of histone acetyltransferases, in asthmatic lung CD4+ T cells, HAT activity decreased significantly and the increased Notch1 and hes-1 expression was reversed. The total H3ac, H4ac, site-specific H3K9ac, H3K14ac, H3K27ac, H3K18ac, H4K16ac and H3K79me3 levels of Notch1 gene promoter decreased significantly, and the H3K4me3, H3K9me3, H4K20me3 levels had no significant difference. We further investigated the suppressive effects of GAR on asthmatic parameters. Results showed that the levels of IL-4, IL-5 and IL-13 were significantly reduced and a small reverse trend was found in the level of IFN-g after GAR treatment. Furthermore, the expression of NF-κB and AP-1 reduced significantly. These results suggest that asthma is associated with changes in the epigenetic status of Notch1 promoter, including abnormal histone acetylation and methylation, and GAR may have applications in the treatment of asthma.

Combination of targeting gene-viro therapy with recombinant Fowl-pox viruses with HN and VP3 genes on mouse osteosarcoma.

BACKGROUND: Osteosarcoma is an aggressive cancerous neoplasm arising from primitive transformed cells of mesenchymal origin that exhibit osteoblastic differentiation and produce malignant osteoid. With the rapid development of tumor molecular biology, gene and viral therapy, a highly promising strategy for the treatment, has shown some therapeutic effects. OBJECTIVES: To study the strategy of cooperative cancer gene therapy, previously, we explored the antitumor effects of recombinant Fowl-pox viruses (FPVs) with both HN (hemagglutinin-neuramidinase) and VP3 genes on mouse osteosarcoma. MATERIALS AND METHODS: We constructed vFV-HN, vFV-VP3 and vFV-HN-VP3 inserting CAV VP3 gene, NDV HN gene into fowlpox virus. S180 osteosarcoma were transfected with Recombinant Fowl-pox viruses (FPVs). These cell lines stably expressing tagged proteins were selected by culturing in medium containing puromycin (2 µg/ml) and confirmed by immunoblotting and immunostaining. S180 osteosarcoma model with BALB/c mice and nude mice were established and the vFPV viruses as control, vFV-HN, vFV-VP3, vFV-HN-VP3 were injected into the tumor directly. The rate of tumor growth, tumor suppression and the sialic acid levels in serum were examined and the tumor tissues were analyzed by the method of immunohistochemistry. Flow cytometric analysis was performed using a FACSCalibur flow cytometer. A total of 100,000 events were analyzed for each sample and the experiment was repeated at least twice. RESULTS: Our data indicated that vFV-HN, vFV-VP3 and vFV-HN-VP3 all had growth inhibition effects, the inhibition rate of vFV-HN-VP3 group was 51.7%, which was higher than that of vFV-HN, vFV-VP3 group and control group (p < 0.01). The sialic acid level of vFV-HN-VP3 group in mouse serum was 4.22±0.27 mmol/l, which was lower than that of other groups (p < 0.01). CONCLUSIONS: These results suggest that genes into mouse osteosarcoma cancer cells can cause cell a specificity anti-tumor immune activity, suppress tumor growth, and increase the survival rate of the tumor within host.

YES-associated protein 1 promotes adenocarcinoma growth and metastasis through activation of the receptor tyrosine kinase Axl.

Yes-associated protein 1 (YAP1), a nuclear effector of the Hippo pathway, plays an important role in tumorigenesis and progression of multiple cancers. The present study aimed to investigate the clinical significance of YAP1 and receptor tyrosine kinase Axl expression in human lung adenocarcinomas (LAC). We further explored possible molecular mechanisms mediated by YAP1 in LAC and gastric adenocarcinoma (GAC) cells. Forty-nine cases of human LAC and normal lung tissue (NLT) were collected. The expression of YAP1 and Axl was assessed by immunohistochemical assay through tissue microarray procedure and the clinicopathologic characteristics of all patients were analyzed. Using a loss of function approach, we investigated the effects of small hairpin RNA (shRNA)-mediated knockdown of YAP1 on the expression of Axl, proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-9 (MMP-9), and the proliferative activities and invasive potential in LAC A549 and GAC SGC-7901 cell lines. As a result, the expression of YAP1 and Axl was found in LAC tissues with higher strong reactivity rate compared to the NLT (87.8 percent vs.60.8 percent, P=0.000; 77.6 percent vs 0.0 percent, P=0.000), but they did not associate with the age, gender, tumor size, TNM staging or lymph node metastases of LAC patients (each P>0.05). Spearman rank correlation analysis showed a positive correlation between YAP1 and Axl expression. Furthermore, knockdown of YAP in vitro markedly down-regulated the expression of Axl, PCNA and MMP-9, and inhibited the proliferation and invasion of LAC and GAC cells. Taken together, YAP1 and Axl are highly expressed in LAC compared to the NLT, and knockdown of YAP1 may inhibit the proliferation and invasion of adenocarcinoma cells through downregulation of the Axl pathway, representing a potential therapeutic target for the treatment of cancer.

[Clinical effect of X-N advancement flap in repairing pressure ulcer on the buttock or back].

Objective: To explore the clinical effect of X-N advancement flap in repairing pressure ulcer on the buttock or back. Methods: From June 2018 to June 2019, 20 patients with grade Ⅳ pressure ulcers on the buttock or back were hospitalized and treated in the Department of Traumatology, Burns and Plastic Surgery of Fourth Affiliated Hospital of Guangxi Medical University, including 15 males and 5 females, aged 48-89 years. The area of the patient's wound was 8 cm×5 cm-15 cm×12 cm after debridement, and all were repaired with the X-N advancement flap designed by the author. The flap was designed according to the direction of skin relaxation on both sides of the wound, and the skin was incised in X-shape and sutured in N-shape. The width and advancement distance of the flap were recorded, and the ratio of the advancement distance to the width of the flap was calculated. The flap survival, complication, and follow-up were observed and recorded. Results: The width of the flap was (5.9±1.2) cm, the advancement distance of the flap was (10.3±2.5) cm, and the ratio of the advancement distance to the width of the flap was 1.8±0.4. All the flaps survived, and none of the flaps had blood flow disorder. Local dehiscence occurred in the flap of one patient 1 week after surgery, which was healed after laying on the floating bed, strengthened care, and wound dressing change. The flap of one patient developed infection 5 days after surgery, which was healed after partial suture removal, smooth drainage, and replacement with sensitive antibiotics. The wounds of the remaining 18 patients were all cured. After 3 months of follow-up, the flaps survived well with good elasticity and texture. Conclusions: The X-N advancement flap can make the skin and soft tissue move forward effectively. It is simple and effective to repair pressure ulcers on the back or buttock of patients with this flap, which is worthy of clinical promotion and application.

MicroRNA-212 participates in the development of prostate cancer by upregulating BMI1 via NF-κB pathway.

OBJECTIVE: To investigate the role of microRNA-212 in prostate cancer (PCa) and its underlying mechanism. PATIENTS AND METHODS: MicroRNA-212 expressions in 72 PCa tissues and paracancerous tissues were detected by qRT-PCR (quantitative real-time polymerase chain reaction). The relationship between microRNA-212 expression and clinical characteristics of PCa patients was analyzed. Target genes of microRNA-212 were predicted by TargetScan and verified by luciferase reporter gene assay. Proliferation, cell cycle, and apoptosis of PCa cells were detected after transfection with corresponding plasmids of microRNA-212 in PCa cells, respectively. The effect of microRNA-212 on BMI1 and NF-κB pathway was detected by Western blot. RESULTS: MicroRNA-212 was downregulated in PCa patients. The survival rate of PCa patients with lower expression of microRNA-212 was remarkably lower than those with a higher level. After overexpression of microRNA-212, we observed inhibited proliferation and arrested cell cycle of PCa cells. Increased apoptosis was found after PCa cells were transfected with microRNA-212 mimic. Luciferase reporter gene assay showed that microRNA-212 was bound to BMI1, which further promoted PCa development via NF-κB pathway. CONCLUSIONS: MicroRNA-212 was downregulated in PCa tissues, which could promote the PCa development by targeting BMI1 via NF-κB pathway.

MicroRNA-373-3p inhibits prostate cancer progression by targeting AKT1.

OBJECTIVE: This study aims to investigate whether microRNA-373-3p could inhibit the progression of prostate cancer (PCa) by targeting and degrading AKT1. PATIENTS AND METHODS: Expression levels of microRNA-373-3p and AKT1 in PCa tissues and benign prostate hyperplasia (BPN) tissues were detected by quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR). According to the follow-up data, survival curves and receiver operating characteristic (ROC) curves were drawn to investigate whether microRNA-373-3p could be served as a biomarker for early diagnosis and prognosis of PCa. The effect of microRNA-373-3p on cell proliferation was examined by cell counting kit-8 (CCK-8) assay. Subsequently, we explored the direct binding condition of AKT1 and microRNA-373-3p by dual-luciferase reporter gene assay and Western blot. RESULTS: QRT-PCR results showed that microRNA-373-3p level was significantly lower in PCa tissues compared with that of BPN tissues, whereas AKT1 expression was significantly increased. By analyzing the survival curve and ROC curve, we found that the overall survival (OS) of PCa patients with higher microRNA-373-3p expression was markedly longer than those with lower expression. Besides, microRNA-373-3p could be used as an early diagnostic marker to distinguish PCa from BPH. Overexpression of microRNA-373-3p in PCa cells (LNCaP and PC3 cells) remarkably inhibited cell proliferation. Dual-luciferase reporter gene assay and Western blot showed that microRNA-373-3p targeted the 3'UTR of AKT1 and inhibited its expression. CONCLUSIONS: Downregulated microRNA-373-3p promoted the proliferation of prostate cancer cells via targeting AKT1.

PRINS Long Noncoding RNA Involved in IP-10-Mediated Allograft Rejection in Rat Kidney Transplant.

BACKGROUND: Previously, high levels of CXCR3+ T-cell recruitment was demonstrated in the prolonged ischemia-accelerated acute allograft rejection in rat kidney transplant. In the present study, the effect of chemokine IP-10 was investigated and the expression of chemokine-related PRINS (Psoriasis susceptibility-related RNA gene induced by stress) lncRNA determined in the allografts subjected to ischemia. METHODS: F344-to-Lewis rat kidney transplantation was performed, and renal grafts were stored for 2 hours or 16 hours. Samples were removed at 24 hours and 7 days after operation. Cellular infiltration was determined with the use of immunohistochemistry, and messenger RNA expression was assessed with the use of real-time polymerase chain reaction. RESULTS: The 16-hour-ischemia kidney displayed acute tubule damage and up-regulation of PRINS lncRNA expression. On day 7, IP-10 expression and CD3-positive T cells were increased in allografts compared with control samples, which were inhibited by the IP-10 antibody treatment accompanied by reduced serum creatinine. CONCLUSIONS: These observations provide evidence for IP-10 in a regulatory role in cold ischemia-elicited acute allograft rejection and in PRINS lncRNA expression. Our data enhance the understanding of the mechanism underlying between prolonged ischemia and acute rejection.