MFAP2 aggravates tumor progression through activating FOXM1/ß-catenin-mediated glycolysis in ovarian cancer.

Ovarian cancer is one of the most common gynecological tumors that seriously endanger the health and quality of life of women. Microfibril-associated protein 2 (MFAP2) has been demonstrated to play crucial roles in the development of multiple tumors. However, the function of MFAP2 in ovarian cancer remains unclear. In this study, we found that MFAP2 was upregulated in ovarian cancer and cells and was positively correlated with FOXM1 and glycolysis-related genes. The results of Cell Count Kit-8, colony formation, and flow cytometry assays indicated that MFAP2 promoted cell proliferation. In addition, MFAP2 promotes cell proliferation, glucose uptake, lactate production; increases ATP levels, extracellular acidification ratio, and oxygen consumption ratio in ovarian cancer cells and increases the expression of glycolytic proteins. Further mechanistic analysis suggests that MFAP2 promotes FOXM1/ß-catenin-mediated glycolysis signaling in ovarian cancer cells. Knockdown of MFAP2 inhibits ovarian cancer xenograft tumor growth and expression of Ki-67, MFAP2, FOXM1, GLUT1, HK2, and ß-catenin in mice. In conclusion, MFAP2 promotes cell proliferation and glycolysis by modulating the FOXM1/ß-catenin signaling pathway in ovarian cancer, which may offer a fresh insight into the treatment of ovarian cancer in the glycolysis pathway.

Heat maps present the spatial distribution of human papillomavirus infection in Zhejiang Province, China.

Determining the spatial distribution of human papillomavirus (HPV) and performing accurate public health analyses helps to distinguish areas of healthcare that require further research, and enables therapeutic techniques and approaches in healthcare to be focused more accurately. A total of 4,560 women were enrolled in the present study. Flow-through hybridization and gene chip assays were used to detect the genotypes of HPV infection. Heat maps were then generated to present the spatial distribution of HPV infections in Zhejiang Province according to genotype. Of the exfoliated cervical cell samples from the 4,560 women, HPV was detected in 1,886 samples. HPV-16, -58, -52 and -18 were the most prevalently identified genotypes in the population included in the present study. HPV-16 and -58 infections were mainly distributed in the northern and central regions of Zhejiang Province, such as in Hangzhou and Shaoxing, where the prevalence was higher than that in the southern regions (P<0.05). HPV-18 infection was widespread throughout Zhejiang Province, but had a much lower infection rate in Ningbo and Huzhou (P<0.05). High infection rates of HPV-52 were mainly detected in Hangzhou and the eastern coastal areas of Wenzhou, with a relatively low rate of infection in the center of the province (P<0.05). In conclusion, HPV-16, -58, -52 and -18 were the four most prevalent HPV genotypes observed in Zhejiang Province. Heat maps were created to display the spatial distribution of HPV infection according to genotype, which varied by geographical regions. The results indicate that for individuals in Ningbo or Wenzhou, bivalent or quadrivalent vaccines may be suitable, but for those in Hangzhou and Shaoxing, nonavalent vaccines are strongly recommended.

Mutational profiling of melanomas in patients from the southeast coast of China.

BACKGROUND: Melanoma is one of the most lethal cancers in China, and the genomic landscape of melanoma in the Asian population is different from Caucasians. METHODS: To better understand the genomic profile of distinct kinds of melanomas in China, we used an NGS platform to analysis of 62 melanomas from the southeast coast of China. RESULTS: The recurrently mutated genes are BRAF (29%), RAS (29%), CTNNB1 (11.3%), KIT (9.7%) and NF1 (8.1%) in the whole group. Among the different types of melanoma, cutaneous melanoma has a high frequency of BRAF mutation (70.6%), NRAS (57.1%) is the top one gene found in the mucosal group. For acral melanoma, except for the RAS family, CTNNB1 mutation (13.2%) first found to be frequently mutated in our cohort and patients with CTNNB1 activating mutation. These results may be related to a more reduced response to immunotherapy, according to the earlier report. CONCLUSIONS: Our study profiled the mutational landscape of melanoma in patients from the southeast coast of China. In addition to the most frequently mutated genes (BRAF, RAS, KIT) reported in other studies, we found some new recurrent gene mutations, such as CTNNB1 mutation in acral melanoma, that had not been reported in other studies.

Myricetin induces apoptosis and enhances chemosensitivity in ovarian cancer cells.

Ovarian cancer is the most lethal type of gynecological cancer and is the fifth leading cause of cancer-associated mortality in females globally. The majority of patients with ovarian cancer suffer from recurrent, progressive disease, due to the acquisition of a resistance phenotype towards various conventional chemotherapy drugs. Although paclitaxel has been demonstrated to be effective against ovarian tumors, there have been reports of the development of a resistant phenotype against Taxol® treatment. The multidrug resistance (MDR)-1/P-glycoprotein has previously been demonstrated to be associated with the acquisition of paclitaxel resistance in certain ovarian tumors. Therefore, the screening of novel drug candidates able to target MDR-1 in ovarian cancer cells and increase the sensitivity to Taxol® is required in order to improve the treatment of this disease. In the present study, the underlying mechanisms by which the dietary flavonoid myricetin enhances the cytotoxic potential of paclitaxel in ovarian cancer cells, was investigated. It was observed that myricetin induced significant cytotoxicity in A2780 and OVCAR3 ovarian cancer cells, with the IC50 value obtained at 25 µM. Myricetin treatment also resulted in the induction of apoptosis in the two cell lines, accompanied by the modulation of certain pro- and anti-apoptotic markers. It was also determined that the pre-incubation of ovarian cancer cells with a lower dose of myricetin was able to increase the cytotoxicity of paclitaxel, due to the significant downregulation of MDR-1 in these cells.

Xiaoaiping combined with cisplatin can inhibit proliferation and invasion and induce cell cycle arrest and apoptosis in human ovarian cancer cell lines.

PURPOSE: The aim of the present study was utilizing Xiaoaiping as a single agent or combined with cisplatin to study its effect on the ovarian cancer cells (HO-8910 and HO-8910PM cells) in tumor cell proliferation, cell apoptosis, cell cycle distribution and cell invasion and migration. METHODS: Both HO-8910 and HO-8910PM cell lines were treated with Xiaoaiping injection, cisplatin or combination. Effects on the cell viability and apoptosis induction were estimated using the Cell counting Kit-8 assay and Annexin V-FITC/Propidium Iodide staining. The distribution of cells in different phases of the cell cycle was assayed using flow cytometry analysis. The effects of Xiaoaiping on the inhibition of cell invasion and migration were researched with Transwell cell migration. RESULTS: Both Xiaoaiping and cisplatin significantly decreased the HO-8910 cell survival versus control arm. Combination treatment showed a higher cytotoxicity to cells in vitro than Xiaoaiping and cisplatin alone. An increase in the G0/G1 phase fraction in HO-8910 cells treated with either Xiaoaiping or cisplatin alone was evident when compared to the fraction in control arm. Compared to the effects of treatment with either agent alone, combination treatment significantly increased the fraction of cells in G0/G1 phase. The HO-8910 cell lines treated with cisplatin demonstrated a significant increase of apoptotic cell rate compared to untreated cell lines. The rate of apoptosis in combined treatment group was significantly higher than that of the single agent treatment groups. A significant reduction in the number of invading cells was observed for Xiaoaiping-treated HO-8910 cells compared with the control group. However, cisplatin did not significantly induce the migration of cells versus untreated cells. Combination of Xiaoaiping and cisplatin significantly suppressed cell invasion and migration versus single-drug treatment in HO-8910 cells. The results of HO-8910PM cells were similar with HO-8910 cells in all tests. CONCLUSIONS: In summary, our results showed that Xiaoaiping as a single agent or combined with cisplatin could induce cell cycle arrest, cause apoptosis and necrosis in ovarian cancer cells, and inhibit cell invasion and migration. The present study also laid a foundation for further investigation involving molecular mechanism. Above all, it may provide a novel therapeutic regimen for ovarian cancer.

Impact of carboplatin plus paclitaxel combined with endostar against A375 melanoma cells: An in vitro and in vivo analysis.

PURPOSE: The aim of the present study was to investigate the efficacy of carboplatin plus paclitaxel (CP) combined with endostar against A375 melanoma cells in vitro and in vivo. METHODS: Effects on the cell viability and apoptosis induction were estimated with the Cell counting Kit-8 assay and Annexin V-FITC/Propidium Iodide staining. Fifty female BALB/c-nude mice with subcutaneous injection of A375 cells were randomized to be treated with normal saline, dacarbazine alone, dacarbazine plus endostar, carboplatin plus paclitaxel, and CP plus endostar. Tumor volume of mice was monitored after injection and survival time was adopted for survival analysis. RESULTS: CP plus endostar significantly decreased the cell survival rate compared with CP (P<0.01). Combination of CP and endostar showed higher cytotoxicity to A375 cells in vitro than endostar plus dacarbazine (P<0.01). The percentage of apoptotic cells in A375 cells treated with CP plus endostar was appreciably higher when compared to CP group (P<0.05). The mean relative tumor size in CP group was definitely larger (p<0.05) than CP plus endostar group. In addition, the mean survival time in CP plus endostar group was notably elevated compared with the CP group (P<0.05). CONCLUSIONS: Our data indicated that treatment with CP plus endostar significantly reduced cell growth and induced a high rate of apoptotic cells in the A375 melanoma cell line. CP and endostar exhibited synergistic anti-tumor activities in A375 melanoma cells in vitro. CP plus endostar suppressed the growth of xenograft tumors and prolonged the survival time of mice with xenograft tumors. Combination of CP and endostar may be a promising treatment for melanoma.

[Splenectomy in epithelial ovarian cancer: analysis of 32 cases].

OBJECTIVE: To investigate the clinicopathologic features, the complications of splenectomy and the survival of epithelial ovarian cancer patients with splenic metastasis. METHODS: A retrospective study was performed of 32 patients with epithelial ovarian cancer who underwent splenectomy for tumor cytoreduction at Zhejiang Cancer Hospital between Jan 1998 and Jun 2006. RESULTS: Of 32 patients, 23 patients (72%) were serous adenocarcinoma and 9 were non-serous adenocarcinoma. According to pathological grade, none was of G1, 11 were of G2, 21 were of G3. Postoperatively, 20 patients were left with no residual tumor, 7 were with < or = 2 cm and 5 were with > 2 cm residual tumor. Postoperative complications developed in 8 patients (25%), including subphrenic abscess, wound infection, gastric perforation, gastrorrhagia, phlebothrombosis, and bowel obstruction. The median follow up was 38 months, estimated 2-year and 5-year overall survival were 70% and 36%. Univariate analysis revealed that histological grade, residual tumor and courses of chemotherapy were influencing factors of the survival (P < 0.05), but multivariate analysis indicated that only residual tumor and courses of chemotherapy independently influenced survival (P < 0.05). CONCLUSIONS: In epithelial ovarian cancer patients with splenic metastasis, low grade serous adenocarcinoma is most common. Splenectomy as part of cytoreductive surgery is associated with modest morbidity and mortality. Residual tumor and courses of chemotherapy are independent factors associated with the prognosis of the patients.