Expression of HIF-1α is a predictive marker of the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer.

Platinum-based, arterial infusion chemotherapy as a neoadjuvant chemotherapy (NACT) followed by hysterectomy may be efficient for the treatment of locally advanced cervical cancer and improve prognosis. It is important to predict whether the NACT would be effective before it is launched. Hypoxia inducible factor-1α (HIF-1α) is the master transcriptional regulator of the cellular response to altered oxygen concentration. HIF-1α protein expression is elevated in numerous human malignancies, contributes to poor disease outcome, and has been reported to induce tumorigenesis and chemoresistance. In the present study, patients with International Federation of Gynecology and Obstetrics stage IIB-IIIB cervical cancer (n=59) between 2008 and 2014 were assessed for HIF-1α expression by immunohistochemistry. Tumor samples were obtained by biopsy before any treatment. A double-path chemotherapy regimen, paclitaxel (intravenous) plus cisplatin (intra-arterial injection into the uterine region), was used as NACT. The patients were then separated into two groups according to NACT response: One group comprised patients with NACT, for whom the response to treatment was efficient resulting in complete/partial remission of the tumor (CR + PR group; n=52), the other group contained patients with NACT, for whom the result of the treatment was a stable/progressive disease (SD + PD group; n=7). HIF-1α expression was tested in paraffin-embedded sections using immunohistochemistry. HIF-1α expression was significantly higher in the SD + PD group compared with the CR + PR group (P=0.029). The overall survival time was significantly longer in the CR + PR group compared with the SD + PD group (P<0.001). When the patients were divided into two groups based on HIF-1α expression levels. Low (weighted score ≤4, n=39) and high (weighted score ≥6, n=20) expression level groups; the low HIF-1α expression group was significantly more susceptible to NACT treatment (P=0.025). Cox hazard analysis revealed that a high level of HIF-1α expression and lymph node metastases were significant independent predictors of poor overall survival (P=0.025, HR=6.354; P=0.020, HR=6.909, respectively). These results indicated that the expression of HIF-1α may be able to predict the efficiency of NACT and may be considered an independent prognostic factor for stage IIB-IIIB cervical cancer.

Effect of China's Universal Two-child Policy on the Rate of Cesarean Delivery: A Case Study of a Big Childbirth Center in China.

China's universal two-child policy was released in October of 2015. How would this new policy influence the rate of overall cesarean delivery (CD) in China? The objective of this paper is to investigate the trend of overall CD rate with the increase of number of multiparous women based on a big childbirth center of China (a tertiary hospital) in 2016. In this study, 22 530 cases from the medical record department of a big childbirth center of China from January 1 to December 31 in 2016 were enrolled as research objects. Electronic health records of these selected objects were retrieved. According to the history of childbirth, the selected cases were divided into primiparous group containing 16 340 cases and multiparous group containing 6190 cases. Chi-square test was carried out to compare the rate of CD, neuraxial labor analgesia, maternity insurance between the two groups; t-test was performed to compare the in-hospital days and gestational age at birth between the two groups. Pearson correlation coefficient was used to evaluate the relationship among observed monthly rate of multiparas, overall CD rate, and Elective Repeat Cesarean Delivery (ERCD) rate. The results showed that the CD rate in multiparous group was 55.46%, which was higher than that in primiparous group (34.66%, P<0.05). The rate of neuraxial labor analgesia in multiparas group was 9.29%, which was lower than that in primiparas group (35.94%, P<0.05). However, the rate of maternity insurance was higher in multiparas group (57.00%) than that in primiparas group (41.08%, P<0.05). The hospital cost and in-hospital days in multiparas group were higher, and the gestational age at birth in multiparas group was lower than in primiparas group (P<0.05). The overall CD rate slightly dropped in the first 4 months of the year (P<0.05), then increased from 36.27% (April) to 43.21% (December) (P<0.05). The rate of multiparas women and ERCD had the same trend (P<0.05). There were linear correlations among the rate of overall CD, the rate of multiparas women and the rate of ERCD rate (P<0.05). With the opening of China's two-child policy, the increasing rate of overall CD is directly related with the high rate of ERCD. Trials of Labor After Cesarean Section (TOLAC) in safe mode to reduce overall CD rate are warranted in the future.

Prevalence and Determinants of High-risk HPV Infection among 11549 Women from an Opportunistic Screening in Hubei Province.

High-risk human papillomavirus (hrHPV) infection plays an important role in the development of cervical intraepithelial neoplasia and cervical cancer. A total of 11 549 women were enrolled from the Maternal and Child Health Hospital of Hubei Province. Each participant accepted hrHPV testing and completed a self-administered questionnaire about basic information and potential risk factors. The univariable and multivariable logistic regression model was used to explore the associations between variants and hrHPV infection. Our results showed that hrHPV prevalence was 16.09% in Hubei Province, among which, hrHPV was more likely to be positive in women aged 51 years or above (OR=1.65, 95% CI: 1.28-2.14), and in women who had symptoms of bleeding after intercourse (OR=1.32, 95% CI:1.17-1.50), had first sexual intercourse at the age of 18 years or below (OR=1.33, 95% CI:1.07-1.64), had at least three male sexual partners (OR=2.50, 95% CI:2.07-3.03), and who had been diagnosed with sexually transmitted infections (OR=1.50, 95% CI:1.12-2.03). Married women (OR=0.66, 95% CI: 0.55-0.78) and women who frequently used condoms (OR=0.75, 95% CI:0.67-0.84) had a relatively lower hrHPV prevalence. This study confirms that hrHPV infection was associated with age, marital status, symptoms of intercourse bleeding, history of sexually transmitted infections, and sex-related behaviors. Above all, this study provides a baseline database prior to obtaining vaccinations for dynamic tracking of the changes in hrHPV prevalence.

Two protein-coding genes act as a novel clinical signature to predict prognosis in patients with ovarian serous cystadenocarcinoma.

Ovarian cancer is the seventh most common type of cancer and the eighth most common cause of cancer-associated mortality among women. A number of studies have hypothesized that the expression status of certain genes may be used to predict prognosis in ovarian cancer. In the present study, the RNA expression data from next-generation sequencing and the clinical information of 413 patients from The Cancer Genome Atlas dataset was downloaded to identify the association between gene-expression level and the survival time of the patients with ovarian serous cystadenocarcinoma. A five-gene model was predicted to be significantly associated with patient survival in ovarian serous cystadenocarcinoma by using random survival forests variable hunting algorithm and Cox analysis. A total of two genes, mesencephalic astrocyte-derived neurotrophic factor and dedicator of cytokinesis 11, of the predicted five genes demonstrated positive expression in the ovarian serous cystadenocarcinoma cancer tissues by polymerase chain reaction analysis. Kaplan-Meier and Receiver Operating Characteristic analysis confirmed that the model of the two genes exhibited high sensitivity and specificity to predict the prognostic survival of patients. In conclusion, the expression of the two genes in the two-gene model was associated with the prognostic outcomes of patients with ovarian serous cystadenocarcinoma; the model demonstrated potential as a novel prognostic indicator, which may have important clinical significance.

[Inhibitory effects of an antisense PCDGF vector on proliferation and invasion of highly malignant ovarian cancer cells and the related mechanism].

OBJECTIVE: To investigate the inhibitory effects of an antisense PC cell derived growth factor (PCDGF) vector on proliferation and invasion of highly malignant ovarian cancer cell lines Sw626 and A2780 cells, and preliminarily explore the related mechanisms. METHODS: MTT assay and Boyden chamber in vitro invasion assay were employed to detect the changes of proliferation and invasion ability in the Sw626 and A2780 cells transfected with anti-sense PCDGF. The expression levels of cyclin D1 and CDK4 proteins before and after transfection were detected by Western blotting. The effects on the expression and activity of MMP-2 were evaluated by quantitative RT-PCR and zymography, respectively. RESULTS: Comparing with the blank group, the proliferation inhibition rate of the Sw626 and A2780 cells transfected with anti-sense PCDGF was 72.9% and 70.9%, respectively, and the invasion ability was inhibited by 62.9% and 59.0%, respectively. The levels of cyclin D1 and CDK4 protein expression in antisense PCDGF transfected cells were 0.38 +/- 0.08 and 0.37 +/- 0.13, respectively, all significantly lower than 0.84 +/- 0.11 and 0.64 +/- 0.11, respectively, in the blank group (P < 0.01). The MMP-2 mRNA expression level in antisense PCDGF transfected cell group was 0.66 +/- 0.11, not significantly decreased in comparison with 0.89 +/- 0.09 in the blank group (P > 0.05), but the activity of MMP-2 was inhibited significantly. CONCLUSION: The antisense PCDGF vector may inhibit markedly the proliferation and invasion of highly malignant ovarian cancer cells, and partially reverses their malignant phenotype. It seems to be related with down-regulating the expression of cyclin D1 and CDK4 and inhibiting the activity of MMP-2. Our findings indicate that PCDGF may become a new target for antisense gene therapy of ovarian cancer.

[Clinical analysis of 21 cases of cervical adenosquamous carcinoma].

OBJECTIVE: To study the clinical characteristics, treatment modalities and prognosis of cervical adenosquamous carcinoma. METHODS: The data of 21 patients with adenosquamous cervical cancer who were admitted into Zhongnan Hospital, Wuhan University from Jan 2001 to Dec 2005 were analyzed retrospectively. Six patients received surgical therapy only and 15 patients received combined therapy. RESULTS: Seven cases were with positive pelvic lymph node metastases and 3 cases were with ovarian metastases. The median survival time of the combined therapy group and surgical therapy group was 54 and 20 months, respectively. In stage I and stage II patients, the median survival time of the combined therapy group and surgical therapy group was 66 and 20 months, respectively. The difference was significant between the two groups (P < 0.05). CONCLUSIONS: Combined therapy should be given to patients with adenosquamous carcinoma of the cervix. Surgical therapy and chemotherapy play an important role in the management and prognosis of adenoquamous carcinoma of cervix. Preserve of ovary for patients with adenosquamous carcinoma of the cervix should only be done when the ovary is confirmed free from any malignant involvement by pathology.

[Management and prognosis of metastatic ovarian carcinoma from nongenital tract].

OBJECTIVE: To study the management and prognosis of nongenital metastatic ovarian carcinoma. METHODS: Thirty-four patients with nongenital metastatic ovarian carcinoma who were admitted in to Zhongnan Hospital of Wuhan University between 1998 and 2004 were analyzed retrospectively. RESULTS: The median survival time of group A (optimal cytoreductive surgery), group B (optimal cytoreductive surgery + chemotherapy), group C (sub-optimal cytoreductive surgery) and group D (sub-optimal cytoreductive surgery + chemotherapy) was 5.0, 10.0, 4.0 and 6.5 months, respectively. The difference was significant between groups A and B, B and C, as well as between group C and D (P < 0.05). CONCLUSIONS: Most of nongenital metastatic ovarian carcinomas come from tumors of stomach and intestine. Optimal cytoreductive surgery and chemotherapy play an important role in the management and prognosis of nongenital metastatic ovarian carcinoma.

[Microsatellite instability and loss of heterozygosity of human leucocyte antigen class I gene in cervical carcinoma].

OBJECTIVE: To investigate the frequency of microsatellite instability (MSI) and loss of heterozygosity (LOH) at human leucocyte antigen(HLA) class I loci in cervical carcinoma and the detailed deletion mapping in this region. METHODS: LOH and MSI of HLA class I genes were analyzed in 30 paired blood and tumor samples by PCR based single-stranded length polymorphism (PCR-SSLP). RESULTS: Of the 30 cases, 23(76.7%) showed LOH at one or more loci. Higher frequencies of LOH were found at four loci: C3_2_11 (50%), C1_4_4 (37%), C1_2_5 (36.7%), D6S276 (48.3%). MSI was found in 20 out of 30 cases (66.7%). CONCLUSION: The data suggest that the LOH and MSI of HLA class I gene might participate in the carcinogenesis of cervical carcinoma. Meanwhile, the minimal deletion region might be defined between C1_2_5 and C3_2_11, thus providing the evidence for cloning the tumor suppressor genes associated with cervical carcinoma.

[Diagnosis and treatment of recurrent epithelial ovarian carcinoma].

OBJECTIVE: To investigate the diagnosis, treatment and prognosis of recurrent epithelial ovarian carcinoma. METHODS: Fifty-two patients with recurrent epithelial ovarian carcinoma who were admitted in Zhongnan Hospital of Wuhan University between 1997 and 2002 were analyzed retrospectively, and their diagnostic methods and the survival rates were compared. RESULTS: The positive diagnostic rate of pelvic examination, CA(125) and ultrasound examination was 73.1%, 84.6% and 53.8%, respectively to the recurrent epithelial ovarian carcinoma. The median survival time of group A (surgery + chemotherapy) and group B (chemotherapy) was 11 and 12 months, respectively. CONCLUSIONS: The diagnostic methods should include pelvic examination, CA(125) and ultrasound examination. We could not know the exact role of surgery to the management and prognosis of recurrent epithelial ovarian carcinoma. Chemotherapy may have an important role to the management and prognosis of recurrent epithelial ovarian carcinoma.