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Objective. Dingkun Pill (DKP) is a proprietary Chinese medicine that has been utilized for patients with gynecological diseases, and its clinical application has been widely accepted in China. However, the effects of DKP on reproduction and metabolism in women with polycystic ovary syndrome (PCOS) have never been systematically evaluated. Our objective was to evaluate the efficacy and safety of DKP in treating reproductive and metabolic abnormalities with PCOS. Methods. We searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and Chinese Biomedical Literature Database up until January 2022 to identify randomized controlled trials (RCTs). The methodological quality of the included RCTs was estimated using the Cochrane collaboration risk-of-bias instrument, and the meta-analysis was performed using RevMan. Results. A total of 22 RCTs (including 1994 participants) were identified. DKP, combined with ovulation-inducing drugs (OID) or combined oral contraceptives (COC) was superior to OID or COC alone in improving the pregnancy rate (relative risk (RR) 1.84, 95% CI 1.62 to 2.11 and RR 1.38, 95% CI 1.16 to 1.64, respectively), ovulation rate (RR 1.38, 95% CI 1.03 to 1.84 and RR 1.23, 95% CI 1.11 to 1.37, respectively), endometrial thickness (weighted mean difference (WMD) 2.50, 95% CI 1.91 to 3.09 and WMD 0.62, 95% CI 0.08 to 1.16, respectively), luteinizing hormone (WMD −1.93, 95% CI −2.80 to−.07 and WMD −1.79, 95% CI −2.66 to−0.92, respectively), and testosterone (standardized mean difference (SMD) −2.12, 95% CI −3.01 to−1.24 and SMD −1.21, 95% CI −1.64 to−0.78, respectively). DKP combined with COC led to a greater improvement in homeostasis model assessment-β (WMD 20.42, 95% CI 16.85 to 23.98) when compared with COC alone. There was a significant difference between DKP and COC in terms of decreasing total cholesterol (WMD −0.37, 95% CI −0.72 to−0.02), triacylglycerol (WMD −0.85, 95% CI −1.50 to−0.20), and free fatty acid (WMD −130.00, 95% CI −217.56 to−42.22). However, DKP did not affect the follicle stimulating hormone, fasting blood glucose, fasting insulin, body mass index, waist-to-hip ratio, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. Adverse reactions were more common in COC alone compared to DKP and COC in combination (RR 0.22, 95% CI 0.07 to 0.63). Conclusion. DKP shows promise in modifying reproductive and metabolic parameters in patients with PCOS and may be used as a primary choice in conventional or complementary therapies for PCOS. The quality of the evidence analyzed was suboptimal, and therefore, our results should be interpreted cautiously. More prospective large-scale and well-designed RCTs, as well as longer intervention durations are required in the future to draw more reliable conclusions.

Purpose: Insulin-like growth factor 1 receptor (IGF-IR) has been implicated in the pathogenesis of ovarian cancer. Ganitumab is an investigational, fully human monoclonal antibody against IGF-IR. Here, we explore the therapeutic potential of ganitumab for the treatment of ovarian cancer.Experimental Design: The effects of ganitumab were tested in vitro against a panel of 23 established ovarian cancer cell lines. The ability of ganitumab to inhibit IGF-I–, IGF-II–, and insulin-mediated signaling was examined in vitro and in tumor xenografts using ovarian cancer models displaying IGF-IR/PI3K/AKT pathway activation by two distinct mechanisms, PTEN loss and IGF-II overexpression. Drug interactions between ganitumab and cisplatin, carboplatin, or paclitaxel were studied in vitro and in vivo.Results:In vitro, growth inhibition varied significantly among individual ovarian cancer cell lines. IGF-II mRNA and phospho–IGF-IR protein expression were quantitatively correlated with response to ganitumab, and PTEN mutations conferred resistance to ganitumab. Ganitumab potently inhibited baseline and IGF-I–, IGF-II–, and insulin-induced IGF-IR and IGF-IR/insulin hybrid receptor signaling in vitro and in vivo. Synergistic and additive drug interactions were seen for ganitumab and carboplatin or paclitaxel in vitro. Furthermore, ganitumab significantly increased the efficacy of cisplatin in ovarian cancer xenograft models in vivo.Conclusions: These observations provide a biologic rationale to test ganitumab as a single agent or in combination with carboplatin/cisplatin and paclitaxel in patients with ovarian cancer. Moreover, assessment of tumor expression of IGF-II, phospho–IGF-IR, or PTEN status may help select patients with ovarian cancer who are most likely to benefit from ganitumab. Clin Cancer Res; 20(11); 2947–58. ©2014 AACR.

PDF file - 114KB, Expression of Akt and PTEN in OV-90 and TOV-21G cells.

PDF file - 56KB, Inhibition of cell growth by ganitumab.

PDF file - 46KB

PDF file - 37KB, Primer sequences.

PDF file - 55KB, Description of ovarian cancer cell lines.

Supplementary Figure S1; Supplementary Table S1; Supplementary Tables S3-S4.

Purpose: PD-0332991 is a selective inhibitor of the CDK4/6 kinases with the ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. Here we investigate the role of CDK4/6 inhibition in human ovarian cancer.Experimental Design: We examined the effects of PD-0332991 on proliferation, cell-cycle, apoptosis, and Rb phosphorylation using a panel of 40 established human ovarian cancer cell lines. Molecular markers for response prediction, including p16 and Rb, were studied using gene expression profiling, Western blot, and array CGH. Multiple drug effect analysis was used to study interactions with chemotherapeutic drugs. Expression of p16 and Rb was studied using immunohistochemistry in a large clinical cohort of ovarian cancer patients.Results: Concentration-dependent antiproliferative effects of PD-0332991 were seen in all ovarian cancer cell lines, but varied significantly between individual lines. Rb-proficient cell lines with low p16 expression were most responsive to CDK4/6 inhibition. Copy number variations of CDKN2A, RB, CCNE1, and CCND1 were associated with response to PD-0332991. CDK4/6 inhibition induced G0/G1 cell cycle arrest, blocked Rb phosphorylation in a concentration-and time-dependent manner, and enhanced the effects of chemotherapy. Rb-proficiency with low p16 expression was seen in 97/262 (37%) of ovarian cancer patients and was independently associated with poor progression-free survival (adjusted relative risk 1.49, 95% CI 1.00–2.24, P = 0.052).Conclusions: PD-0332991 shows promising biologic activity in ovarian cancer cell lines. Assessment of Rb and p16 expression may help select patients most likely to benefit from CDK4/6 inhibition in ovarian cancer. Clin Cancer Res; 17(6); 1591–602. ©2011 AACR.

PDF file - 47KB, Expression analysis in ovarian cancer cell lines.

PDF file - 53KB, IGF1R and INSR signaling in OV-90 and TOV-21G cell lines.

Supplementary Table S2.

Ultrathin fluoroacrylic emulsion coating wrapped effective microporous non-woven air filtration membranes of 0.2 μm thickness were made for PPE masks with up to 99.9% filtration efficiencies for both 0.3 μm NaCl aerosol particles and oily DEHS aerosols. An ultrasonic dip-coating process was applied for the controllable formation of a nano-protrusion morphology on the fiber surface.

Numerous studies have implicated Gα-interacting, vesicle-associated protein (GIV) in the development and metastasis of various cancers. However, its role remains unclear in liver hepatocellular carcinoma (LIHC). We aimed to demonstrate the relationship between GIV and LIHC based on The Cancer Genome Atlas database. We use the Gene Expression Profiling Interactive Analysis and UALCAN to explore the expression of GIV and the survive analysis of GIV in patients with LIHC, genetic alteration analysis, immune infiltration analysis, functional enrichment, protein-protein interaction network analyses, and transcription factor targets of GIV-correlated genes and GIV-interacting genes were performed this study. GIV expression was significantly elevated in LIHC tissues. Remarkable correlation was established between GIV expression and LIHC pathological stage. Low expression of GIV in tumor tissues had a better prognosis than GIV-high expression. GIV alteration frequency was 1.44% in patients with LIHC. GIV-unaltered patients had better survival than GIV-altered ones. Moreover, GIV expression level in LIHC significantly correlated with the infiltration level of immune cells and cancer-associated fibroblasts. The functions of differentially expressed GIVs are associated with the cell cycle pathway. Our data imply that E2F4, E2F1, MYC, and MYCN are key transcription factors for GIV-correlated genes and GIV-interacted genes. GIV may be an adverse prognostic factor for patients with LIHC; it also can be a potential therapeutic target against LIHC. Further studies are required to validate our findings.

Purpose: TRAF3IP3 is involved in the maturation of immune cells, the development of immune tissues and the immune response of the body. TRAF3IP3 is shown to expressed in a variety of malignant tumor cell lines. Down-regulated expression of TRAF3IP3 in malignant melanoma can inhibit tumor growth. However, the role of TRAF3IP3 in glioma is still unknown. In this study, we aimed to study the relationship between TRAF3IP3 and glioma based on TCGA data.Method: We used the Wilcoxon rank sum test to compare the expression of TRAF3IP3 in glioma and normal tissues. Subsequently, Kruskal-Wallis test, Wilcoxon rank sum test, and logistics regression were used to evaluate the relationship between TRAF3IP3 and clinicopathological parameters of glioma patients. GSEA was used to verify the key signal pathways involved in TRAF3IP3. We used the ssGSEA method to analyze the relationship between the expression level of TRAF3IP3 and the immune infiltration in the glioma tumor microenvironment. Finally, we used Kaplan-Meier and COX regression to evaluate the prognostic value of TRAF3IP3.Results: TRAF3IP3 transcription level was highly expressed in gliomas(PConclusion: TRAF3IP3 may play an important role in the occurrence and development of glioma, and may be a potential biomarker for the diagnosis and prognosis of glioma.

Purpose: This study investigated liver enzymes, bile acid metabolism, and liver fibrosis in nonalcoholic fatty liver disease (NAFLD) to evaluate the therapeutic effects of microecological preparations on fatty liver. Methods: Liver enzymes, liver fibrosis, and bile acids were assessed in 40 healthy volunteers and 124 NAFLD patients. All patients were retested for liver enzymes, bile acids, and liver fibrosis after two months of bifid triple viable capsule therapy. Results: (1) Prior to treatment, alanine aminotransferase, aspartate aminotransferase, glutamyl transpeptidase, FibroScan liver stiffness, total bile acid, chenodeoxycholic acid, deoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, and taurolithocholic acid increased with the severity of NAFLD (P

Breast cancer is one of the most common malignant tumors of women. Modern combinatorial therapeutic regimens can reduce patient tumor burdens to undetectable levels, yet in many cases these tumors will relapse. Understanding of breast cancer biology, developing more potent therapeutic approaches, and overcoming resistance are of great importance. WNT5A is a non-canonical signaling member of the WNT family. Its role in breast cancer still remains unclear. Most of the evidence shows that WNT5A is a suppressor in breast cancer and loss of its expression is associated with poor prognosis, while some evidence suggests the tumorigenicity of WNT5A. WNT signaling molecules are potent targets for treatment of cancer. Therefore, understanding the role of WNT5A in breast cancer may provide new ideas and methods for breast cancer treatment. We review the evidence concerning WNT5A and breast cancer involving the signaling pathways and the molecular-targeted therapy of WNT5A. Our results show that the role WNT5A plays depends on the availability of key receptors and intercellular interactions among different cell types.