Inositol monophosphatase 2 promotes epithelial ovarian cancer cell proliferation and migration by regulating the AKT/mTOR signaling pathway.

Ovarian cancer is the third most common malignancy in the gynecological reproductive system. Epithelial ovarian cancer (EOC) represents one of the most common subtypes of ovarian cancer. Once diagnosed, the treatment strategies for EOC are limited, and the prognosis is often poor. Recently, inositol monophosphatase 2 (IMPA2) was found to act as an oncogene in cancer development. However, the role of IMPA2 in EOC is unclear. In the present study, the role of IMPA2 in EOC development was assessed through numerous experiments, including knockdown and MTT assays; multiparametric high-content screening; colony formation, apoptosis and Transwell assays, and a xenografted mouse model. IMPA2 was shown to be critical for EOC cell proliferation, growth, migration and tumorigenesis. In addition, experiments showed that knockdown of IMPA2 expression significantly suppressed proliferation and colony formation in the ES-2 and SKOV3 cell lines in vitro. IMPA2 knockdown also suppressed the migration and invasion of the EOC cell lines, and apoptosis was induced. In vivo, IMPA2 knockdown reduced the tumorigenesis of the EOC cells. Mechanistically, IMPA2 knockdown suppressed the AKT/mTOR signaling pathway and epithelial-mesenchymal transition (EMT). Collectively, the results from the present study demonstrated that IMPA2 may be a novel oncogene in EOC cells via regulation of the AKT/mTOR pathway and EMT.

Distribution of human papillomavirus (HPV) genotypes detected by routine pap smear in Uyghur-Muslim women from Karasay Township Hotan (Xinjiang, China).

HPV infection is an important public health problem in developing countries. We investigated HPV genotypes in the Uyghur female population of Karasay Township, Hotan region. A population-based cervical cancer screening was conducted for 4,500 women in Karasay Township, Xinjiang Hotan, China. A total of 900 women were selected by systematic sampling with a 5:1 proportion (ages 20-69). The subjects completed a questionnaire and consented to HPV typing and Pap smear examination. Colposcopic biopsies were performed for patients with cytological abnormalities (≥ ASCUS). A total of 117 of the 900 women (13%) assessed were infected with HPV. The most common subtype was HPV-16, and other common high-risk types included HPV-58 and HPV-39. A total of 40 women (4.44%) were identified with abnormal cytology (≥ ASCUS) by Pap smear. A significant link was found between HPV prevalence and cytological diagnosis. The HPV infection rates for the patients with cervical inflammation, CIN, and cancer were 18.18%, 64.71%, and 100%, respectively. Significant differences in HPV infection rates were found among the patients with the three groups of pathological results. In Karasay, the HPV infection rate in Uyghur women is lower than previously reported; however, the proportion infected with HR-HPV is higher. HPV-16, HPV-58, and HPV-39 are the most prevalent genotypes.

Serum carotenoid, retinol and tocopherol concentrations and risk of cervical cancer among Chinese women.

BACKGROUND: Despite many epidemiological studies on the effects of dietary antioxidant micronutrients on risk of cervical cancer, the findings remain uncertain and little evidence is available for serum nutrient markers. The present study aimed to examine the relationship between serum carotenoid, retinol and tocopherol concentrations and risk of cervical cancer among Chinese women. MATERIALS AND METHODS: We conducted a hospital-based case- control study in which 358 adults (158 incident cases and 200 controls) were recruited from Xinjiang, China. Serum levels of carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene and lutein/zeaxanthin), retinol, and tocopherols (α-tocopherol and γ-tocopherol) were assessed by reverse-phase high-performance liquid chromatography. RESULTS: We found inverse associations between serum carotenoid (α-carotene, ß-carotene, and lutein/zeaxanthin) and tocopherol (α-tocopherol) concentrations and the risk of cervical cancer after adjusting for potential confounders, but a null association for retinol. The ORs for 1-SD increase were 0.71 (95% CI: 0.56- 0.92; p=0.003) for total carotenoids and 0.75 (95% CI: 0.60-0.94; p=0.008) for total tocopherols. CONCLUSIONS: These results show that higher serum concentrations of some carotenoids and tocopherols are associated with a lower risk of cervical cancer among Chinese women.

Anti-carcinogenic effects of the phenolic-rich extract from abnormal Savda Munziq in association with its cytotoxicity, apoptosis-inducing properties and telomerase activity in human cervical cancer cells (SiHa).

BACKGROUND: Abnormal Savda Munziq (ASMq) is a herbal preparation used in Traditional Uighur Medicine for the treatment cancer. The polyphenol is main compounds contained in ASMq preparation responsible for anticancer effect of ASMq. METHODS: In this study,Real-time quantitative Polymerase Chain Reaction (RT-PCR) assay, MTT assay and flow cytometry were used to investigate the effect of polyphenol of ASMq on cell viability and the potential of the phenolic rich extracts of ASMq to induce apoptosis in human cervical cancer cells SiHa and its effects on telomerase activity were investigated. Cellular morphological change was observed by phase contrast microscopy. The MTT cell viability data revealed that treatment with phenolic rich extracts at 75 ~ 175 µg/ml significantly inhibited the viability and proliferation of cells, and these effects occurred in a concentration-dependent manner and time dependent manner (P < 0.01). RESULTS: The phenolic rich extracts can induce apoptosis of SiHa cells, can increase the apoptosis rate in a concentration-dependent manner and time dependent manner (P < 0.01). Growth inhibition and apoptosis induction by phenolic rich extracts treatment on SiHa cells was associated with down-regulation of anti-apoptotic Bcl-2 expression and telomerase (P < 0.05) and Survivin expression. In addition, phenolic rich extracts exerted a dose-dependent induction of FHIT expression. CONCLUSION: These results suggest that phenolic rich extracts may have anti-tumor effects in human cervical cancer through cytotoxicity, apoptosis-inducing properties and telomerase activity.

Risk factors of lymph node metastasis in low-grade endometrial carcinoma and their correlation with the prognosis of the disease / 医学研究生学报

Objective Controversies exist as to the influences of the characteristics of lymph node metastasis ( LNM) on the prognosis of low-grade endometrial carcinoma ( LGEC) .The aim of this study was to investigate the risk factors of LNM and their im-pact on the prognosis of LGEC. Methods This study included 218 LGEC patients treated by retroperitoneal lymph node dissection. We analyzed the pathologic characteristics of LNM and its relationship with the survival rate of the patients. Results LNM was ob-served in 37 of the 218 patients (16.97%), including 20 cases of pelvic (54.05%), 6 cases of para-aortic (16.22%), and 11 ca-ses of both pelvic and para-aortic ( 29.73%) LNM.Independent risk factors of LNM included deep myometrial infiltration ( OR:5.21, 95%CI:2.77-9.81), cervical stromal involvement (OR:3.15, 95% CI:1.12-8.35), lymphovascular invasion (OR:1.15, 95%CI:1.02-1.30), and abnormally high serum CA125 (OR:3.46, 95%CI:1.56-7.67) (P<0.05).There were sig-nificant differences in the 3-year survival rate between the patients with LNM and those without LNM (83.8%vs 95.0%, P<0.05) as well as in the 3-year tumor-free survival rate (73.0% vs 90.1%, P<0.05). Conclusion Deep myometrial infiltration, cervical stromal involvement, lymphovascular invasion, and abnormally high serum CA125 are the risk factors of LNM in LGEC patients, and LNM affects the prognosis of the LGEC patients.

Mechanisms of hela cell apoptosis induced by abnormal Savda Munziq total phenolics combined with chemotherapeutic agents.

OBJECTIVE: To investigate the effects of abnormal Savda Munziq (ASMq) total phenolics combined with cisplatin and docetaxel on the Hela cell growth. METHODS: In vivo cultured Hela cells were treated with cisplatin, docetaxel, total phenolics, cisplatin+total phenolics or docetaxel+total phenolics. MTT was performed to assess inhibition of cell proliferation, flow cytometry to detect apoptosis, and semi-quantitative RT-PCR to test for survivin and Bcl-2 expression. RESULTS: The total phenolics, cisplatin and docetaxel had significant inhibitory and apoptosis-promoting effects on Hela cells (P<0.05), with the early apoptotic rates of 12.8±0.70%, 18.9±3.79% and 15.8±3.8)%; the total phenolics, cisplatin and docetaxel significantly decreased the expression of Bcl-2 and survivin (all P<0.01), especially when used in combination. CONCLUSION: ASMq total phenolics, combined with cisplatin and docetaxel, could promote the apoptosis of Hela cells possibly through reducing the expression of Bcl-2 and survivin.

The association of a distinct plasma proteomic profile with the cervical high-grade squamous intraepithelial lesion of Uyghur women: a 2D liquid-phase chromatography/mass spectrometry study.

OBJECTIVE: To identify plasma protein biomarkers of cervical high-grade squamous intraepithelial lesion (HSIL) of Uyghur women by proteomics approach. METHODS: Plasma protein samples of Uyghur women with HSIL and chronic cervicitis were analyzed with 2D HPLC followed by detection of target proteins with Linear Trap Quadrupole Mass Spectrometer (LTQ MS/MS). RESULTS: We detected three upregulated and one downregulated protein peaks representing protein constituents distinguishing HSIL from controls by 2D HPLC, identified 31 target proteins by LTQ MS/MS. Further confirmed analysis with online software IPA® 8.7 and ELISA assay showed APOA1 and mTOR as potential biomarkers. CONCLUSIONS: A distinct plasma proteomic profile may be associated with HSIL of Uyghur women.

Establishment and characterization of a new carcinoma cell line from uterine cervix of Uyghur women / 中华病理学杂志

<p><b>OBJECTIVE</b>To establish a uterine cervical carcinoma cell line of Uyghur ethnical background and to evaluate the related biological characteristics for future biomedical investigations of diseases in the Uyghur population.</p><p><b>METHODS</b>Poorly-differentiated squamous cell carcinoma specimens of Uyghur patients were obtained and cultured in vitro by enzymatic digestion method, followed by continuous passaging to reach a stable growth determined by cell viability and growth curve. Morphological study, cell cycling and chromosomal analysis were performed. Tumorigenesis study was conducted by inoculation of nude mice. Biomarker (CK17, CD44, Ki-67, CK14 and vimentin) expression was detected by immunofluorescence and immunocytochemical techniques.</p><p><b>RESULTS</b>A cervical carcinoma cell line was successfully established and maintained for 12 months through 70 passages. The cell line had a stable growth with a population doubling time of 51.9 h. Flask method and double agar-agar assay showed that the cell line had colony-forming rates of 32.5% and 15.6%, respectively. Ultrastructural evaluation demonstrated numerous cell surface protrusions or microvilli, a large number of rod-shape structures in cytoplasm, typical desmosomes and nuclear atypia. Chromosomal analysis revealed human karyotype with the number of chromosomes per cell varying from 32 - 97 with a majority of 54 - 86 (60.3%). Xenogeneic tumors formed in nude mice showed histological structures identical to those of the primary tumor. The cells had high expression of CK17, CD44, Ki-67 and vimentin but no CK14 expression.</p><p><b>CONCLUSIONS</b>A cervical carcinoma cell line from a female Uyghur patient is successfully established. The cell line has the characteristics of human cervical squamous cell carcinoma, and it is stable with maintaining the characteristic biological and morphological features in vitro for more than 12 months, therefore, qualified as a stable cell line for further biomedical research.</p>

Distribution of HLA-DRB1 allele polymorphism in the Uyghur women with family history of cervical cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the distribution of HLA-DRB1 allele polymorphism in Uyghur women with family history of cervical cancer, and provide theoretical evidence for detection and follow-up of high risk persons for cervical cancer by detection of HLA-DRB1 allele polymorphism.</p><p><b>METHODS</b>The HLA-DRB1 13 alleles were detected in 1000 Uyghur women, all from Hotan Moyu county Karsay village by using polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) assay.</p><p><b>RESULTS</b>The frequencies of HLA-DRB1*15 in women with family history of cervical cancer (17.3%), mother (18.0%) and other relatives except mother (17.0%) who had suffered from cervical cancer were significantly higher than that in the control group (9.7%, all P < 0.05). The frequencies of HLA-DRB1*04 in women with family history (16.8%) and other relatives except mother (20.7%) were significantly higher than that in the control group (12.7%, all P < 0.05). The frequencies of HLA-DRB1*03 in women with family history (2.6%) and other relatives except mother (1.1%) were significantly lower than that in the control group (6.3%, all P < 0.01). The frequencies of HLA-DRB1*12 in women with family history of cervical cancer (2.3%) and mother suffered from cervical cancer (1.5%) were significantly lower than that in the control group (5.7%, all P < 0.05). The frequencies of HLA-DRB1*14 in women with family history of cervical cancer (5.4%) and mother who suffered from cervical cancer (3.0%) were significantly lower than that in the control group (8.4%, all P < 0.05).</p><p><b>CONCLUSIONS</b>There are similarity and difference in distribution of HLA-DRB1 allele polymorphisms between the Uyghur women with family history of cervical cancer from Hotan Moyu county and those from southern Xingjiang area. In general, the distribution of HLA-DRB1 allele polymorphism in women with family history of cervical cancer is similar to that reported in abroad. The results of this study support the role of susceptible and protective HLA gene detection in screening high risk persons for this cancer among Uyghur women from cervical cancer high risk areas in Xinjiang.</p>

[Study on the distribution of HPV subtypes in Uighur people living in the Karsay township, Moyu county, Xinjiang].

OBJECTIVE: To study the distribution of human papilloma virus (HPV) subtypes in Uyghur people from the high risk region of cervical cancer in Xinjiang. METHODS: 21 subtypes of HPV from 400 cases of men's swabs of penile and 400 cases of women's cervix swabs were detected, using flow-through hybridization and gene chip technology. RESULTS: (1) The positive rate of HPV among the 400 women cases was 14.25%, with HPV16 the most common type. In women whose HPV was positive, the positive rate of HPV16 was 66.67%. The ranking of frequencies on the HPV subtypes in women were:HPV16, 58, 39, 18, 33, 52, 43, 66, CP8304, HPV6 and 11. (2) Among the 400 male cases, the positive rate of HPV was 8.00%, with HPV16 the most common type. In men whose HPV was positive, the rate of HPV16 was 44.44%. The ranking of HPV subtypes in men were HPV16, 43, 33, 39, 6 (HPV39 and 6 are equivalent) and 53. (3) Both wives and husbands were infected by different subtypes of HPV, the positive rate was relatively low among men whose wife's HPV were positive. However, the HPV positive rate was relatively low among women whose husband's HPV were positive. The concordance infection rate of women and men were 7.02% and the concordance infection rate of men and women were 9.38%. CONCLUSION: The HPV positive rates were relatively low in both men and women living in the region with high risk of cervical cancer in Xinjiang. However, the positive rate of high risk types HPV and HPV16 in both men and women were relatively high. Uyghur men seemed to have played a certain role related to the carcinogenesis of cervical cancer. HPV16 was the main type in both men and women in Xinjiang.

The spectrum of HPV infection in Xinjiang Uighur women with cervical cancer / 肿瘤

Objective: To investigate the difference in distribution of subtypes of Human papilloma virus (HPV) between cervical cancer patients and normal controls of Xinjiang Uighur women and analyze the HPV spectrum in Xinjiang Uighur women suffered from cervical cancer. Methods: Three hundred and thirty Uighur women with cervical cancer and one hundred normal healthy women were recruited in this study. Flow-through hybridization and gene chip (HybriMax) technology was used to detect the twenty one subtypes of HPV. Results: (1) The positive rate of HPV infection including simple infection and multiple infection was 85.15% (281/300) and 7.0% (7/100) in cervical cancer group and control group, respectively. The positive rate of HPV16 infection was 94.31% indicating it was the most common infection in HPV-positive cervical cancer patients. The infection rate was 5.34% for HPV18, 3.91% for HPV68, 2.49% for HPV45, 2.49% for HPV58, 2.14% for HPV39, 1.07% for HPV31, 1.07 for HPV56, and 0.36 for HPV59. There was significant difference in the total infection rate and the HPV16 infection rate between cervical cancer patients and controls (P0.05 ). Although the positive rate of multiple infection of HPV tended to increase but the difference was not significant. Conclusion: HPV16 infection was the most common in cervical cancer patients and normal controls of Xinjiang Uighur women. The next most common types of HPV were HPV18 and HPV68. Xinjiang Uighur women had the relatively higher risk of suffering HPV68 infection indicating the specificity of HPV infection in Uighur women.

Distribution of human papillomavirus and its subtypes in tissue samples of Uigur cervical cancer from southern Xinjiang / 中国癌症杂志

Purpose:To study the association between human papillomavirus (HPV) and cervical cancer in Uigur women from southern Xinjiang where there is a high risk of cervical cancer.Methods:HPV-C,HPV16,HPV18 and HPV6/ 11 were detected in 40 fresh tissues of cervical cancer and 40 tissues of normal cervix by using polymerase chain reaction technique.Results:The positive rate of HPV-C,HPV16,HPV18 and HPV6/11 in fresh tissue of cervix cancer were 87. 5%,72.5%,10.0% and 0,respectively;The positive rate of HPV-C,HPV16,HPV18 and HPV6/11 in normal cervix were20.0%,5.0%,0 and 7.5%,HPV16 was the most common type in HPV-C positive patients with the rate of 82.8 %. The positive rate of HPV-C and HPV16 in cervical cancer were significantly higher than that in control groups;The positive rate of HPV16 in squamous cancer of cervix was significantly higher than that in adenocarcinomas of cervix;while the posi- tive rate of HPV 18 in adenocarcinomas of cervix was significantly higher than that in squamous cancer of cervix(P0.05).Conclusions:HPV16 infection plays an important role in the carcinogenesis of cervical cancer of Uigur women from Southern Xinjiang,HPV16 infection is closely correlated with squamous carcinomas of cervix,while HPV18 infection is closely correlated with adenocarcinomas of cervix.The positive rate of HPV-C and HPV16 have no correlation with clinical stages and histological grade of cervical carcinomas.