The study objective was to examine the association between phentermine/topiramate therapy and weight loss and adverse events in adults with overweight or obesity by meta-analysis and systematic review. Methods: Medical Subject Headings and free-text terms were selected to search for eligible trials in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase up to April 18, 2020. The quality of randomized controlled trials was evaluated by the Cochrane riskof-bias tool. Meta-analysis was performed using random-effect models. Results: Phentermine/topiramate therapy resulted in an average weight loss of 7.73 kg (95% CI: 6.60-8.85) in general compared with placebo. The weight loss was related to the dose of phentermine/topiramate. Compared with placebo, the average weight loss was 3.55 kg (95% CI:

No abstract

MiR-378g enhanced radiosensitivity partially by targeting SHP-1 in NPC cells. Cell invasion was also partially inhibited by miR-378g, but the effect was not mediated by SHP-1.

Background : In the various cancer, mast cells (MCs) infiltration is correlated with a worse prognosis. There is an increasing evidence that MCs and their mediators are participated in remodeling of the tumor microenvironment and facilitate tumor growth, epithelial-to-mesenchymal transition (EMT) and metastasis. Methods : The transwell was conducted to evaluate the correlations between MCs and non-small cell lung cancer (NSCLC) cells in vitro. The RNA interference of β-catenin was performed to further explore the signaling pathway. Lung adenocarcinoma cell line A549 and human MC (HMC-1) were subcutaneously injected into BALB/c nude mice. The conventional experiment methods (such as quantitative RT-PCR Western Blot, Immunofluorescence, and ELISA) were used in the present study. Results : We found that high density of MCs in NSCLC correlates with worse prognosis. The NSCLC cells could release CCL5 and recruit MCs to the tumor microenvironment. Then, we explored that HMC-1 transplantation accelerated the growth of A549 cell in nude mice. Moreover, the MCs-derived factors were responsible for tumor growth. When NSCLC cells were activated, MCs produced various factors that induced EMT and migration. We also identified that CXCL8/interleukin (IL)-8 served as the major modulator containing in the activated MC conditioned medium. Furthermore, MCs and exogenous IL-8 promoted β-catenin phosphorylation in NSCLC cells. Inhibiting the Wnt/β-catenin pathway by RNA interference could revert EMT and migration of NSCLC. Conclusions : Our study suggests that MCs are recruited into NSCLC microenvironment and improve the EMT and migration of cancer cells, thereby accelerating the growth of NSCLC.

The present study aimed to investigate the influence of microRNA-4649-3p on nasopharyngeal carcinoma (NPC) cell proliferation and how it regulated SHP-1 expression. The online software TargetScan was used to predict the microRNAs targeting SHP-1 and identified that miR-4649-3p was one of the possible miRNAs targeting SHP-1. Subsequently, quantitative polymerase chain reaction (PCR) was used to detect the expression level of miR-4649-3p and SHP-1 mRNA in different NPC cell lines. The miR-4649-3p mimics and inhibitors were transfected into NPC cells and cell proliferation was examined by the MTT assay. The SHP-1 expression level was determined by PCR and western blot analysis. Lentivirus containing the SHP-1 gene and miR-4649-3p mimics was co-transfected into the NPC cells and cell proliferation was detected by the MTT assay. The expression level of miR-4649-3p and SHP-1 mRNA was negatively correlated in the NPC cell lines. miR-4649-3p mimics suppressed NPC cell proliferation whereas miR-4649-3p inhibitors promoted NPC cell proliferation. The SHP-1 expression level was suppressed when transfected with miR-4649-3p mimics in NPC cells. The miR-4649-3p inhibitors increased SHP-1 expression. The luciferase reporter assay showed that miR-4649-3p directly targeted SHP-1 by binding to the 3'-untranslated region of SHP-1 mRNA. Overexpression of SHP-1 inversed the inhibited effect of miR-4649-3p mimics on cell proliferation. In conclusion, miR-4649-3p inhibits cell proliferation by targeting SHP-1 in NPC cells.

BackgroundRadioresistance is the main limit to the efficacy of radiotherapy in nasopharyngeal carcinoma (NPC). SHP-1 is involved in cancer progression, but its role in radioresistance and senescence of NPC is not well understood. This study aimed to assess the role of SHP-1 in the radioresistance and senescence of NPC cells.MethodsSHP-1 was knocked-down and overexpressed in CNE-1 and CNE-2 cells using lentiviruses. Cells were irradiated to observe their radiosensitivity by colony forming assay. BrdU incorporation assay and flow cytometry were used to monitor cell cycle. A β-galactosidase assay was used to assess senescence. Western blot was used to assess SHP-1, p21, p53, pRb, Rb, H3K9Me3, HP1γ, CDK4, cyclin D1, cyclin E, and p16 protein expressions.ResultsCompared with CNE-1-scramble shRNA cells, SHP-1 downregulation resulted in increased senescence (+107 %, P < 0.001), increased radiosensitivity, higher proportion of cells in G0/G1 (+33 %, P < 0.001), decreased expressions of CDK4 (−44 %, P < 0.001), cyclin D1 (−41 %, P = 0.001), cyclin E (−97 %, P < 0.001), Rb (−79 %, P < 0.001), and pRb (−76 %, P = 0.001), and increased expression of p16 (+120 %, P = 0.02). Furthermore, SHP-1 overexpression resulted in radioresistance, inhibition of cellular senescence, and cell cycle arrest in the S phase. Levels of p53 and p21 were unchanged in both cell lines (all P > 0.05).ConclusionSHP-1 has a critical role in radioresistance, cell cycle progression, and senescence of NPC cells. Down-regulating SHP-1 may be a promising therapeutic approach for treating patients with NPC.

Although the inhibitor of apoptosis protein-like protein-2 (ILP-2) has been shown as a serological biomarker for breast cancer, its effect on breast cancer cell growth remains elusive. The present study aimed to determine the role of ILP-2 in breast cancer cell growth. We used immunohistochemistry to analyze ILP-2 expression in 59 tissue paraffin-embedded blocks, which included 35 breast cancer tissues and 24 galactophore hyperplasia tissues. Western blot analysis was used to detect protein expression levels of ILP-2 in breast cancer cell lines such as HCC-1937, MX-1 and MCF-7 as well as breast gland cell line MCF 10A. ILP-2 was silenced by siRNA in HCC-1937, MX-1 and MCF-7 cell lines. MTT assays, scratch assays and AO-EB double staining analysis were conducted to evidence the role of ILP-2 on breast cancer cell growth. Results from this study showed increased ILP-2 expression in breast cancer tissues and breast cancer cell lines such as HCC-1937, MX-1 and MCF-7. Cell viability or rate of cell migration of HCC-1937, MX-1 and MCF-7 cell lines was significantly inhibited when ILP-2 was knocked down by siRNA. The apoptosis rate of HCC-1937, MX-1 and MCF-7 cell lines was increased when compared with that of the control group. Thus, ILP-2 plays an active role in the growth of breast cancer cells.

Background: An increasing amount of evidence has demonstrated that combined or multiple targeted therapies could bring about more durable clinical outcomes, and it is known that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance is related to bypass activation. This study aims to explore a specific solution for third-generation EGFR-TKI resistance caused by bypass activation, and to examine the antitumor effects of the combination of a novel inhibitor CX-6258 HCl with osimertinib, along with its underlining mechanisms.Methods: A bioinformatics analysis was performed to detect the relations between the provirus integration site for Moloney murine leukemia virus 1 (PIM1) expression and prognosis of lung cancer. The EGFRmutated lung cancer cell lines were treated with the combination of CX-6258 HCl and osimertinib to analyze cell proliferation using the Cell Counting Kit-8, colony formation, and in vivo experiments. Cell migration was analyzed using wound healing and Transwell assays. The apoptosis level was detected using Annexin V-propidium iodide flow cytometry. The expression levels of EGFR and STAT3 were determined using Western blot analysis.Results: High expression level of PIM1 was related to the poor prognosis of non-small cell lung cancer (NSCLC). The combined administration of osimertinib and CX-6258 HCl significantly inhibited cell proliferation and migration and effectively induced apoptosis in lung cancer cells. It was more efficient in suppressing EGFR activation and phosphorylation of STAT3 compared with osimertinib treatment alone.Furthermore, it showed a durable efficacy in a xenograft model. Conclusions:This study showed that PIM1 is a poor prognostic factor for NSCLC. CX-6258 HCl is a potential molecular inhibitor to sensitize the antitumor effects of osimertinib through the inhibiting of the phosphorylation of STAT3 in NSCLC.