Clinical characteristics and prognostic characterization of endometrial carcinoma: a comparative analysis of molecular typing protocols.

BACKGROUND: Endometrial carcinoma (EC) is one of the most common gynecological malignancies in China and globally, accounting for the fourth-prevalent cancer in women. Although numerous studies have confirmed prognostic value of The Cancer Genome Atlas (TCGA) molecular subgroups, it is unclear how they are combined with histological features. The main objective of this study was to compare ProMisE and TCGA classification for the rapid and accurate prediction of prognosis within EC patients, together with the provision of a revised strategy for individualized diagnosis and treatment of patients. METHODS: Within this study, 70 patients with EC from Beijing Tsinghua Changgeng Hospital (affiliated to Tsinghua University) were retrospectively examined between July 2015 and December 2021. Samples were processed for determination of clinical markers, together with ProMisE and TCGA classification. RESULTS: Comparative analysis across four TCGA types (POLE, Low-CN, High-CN, and MSI-H) and age, was statistically significant (χ²= 7.000, p = 0.029). There was no significant difference observed among the four TCGA types and FIGO stage, vascular invasion and depth of invasion, or lymph node metastasis and tumor area. There was no significant association between the expression of Vimentin, Ki-67, PTEN, MSH2, PAX-8, ß-catenin, CD10, ER, PR, P16, MLH1, and PMS2 with the four TCGA types. In addition, p63 expression (χ²= 11.09, p = 0.029) and p53 expression (χ²= 11.585, p = 0.005) were statistically significant. Numerous models demonstrated that patients with POLE mutations and low-CN had higher progression free survival (PFS) and overall survival (OS), whereas those with high-CN had lowest values. The log-rank test revealed that the survival rate of PR-positive and ER-positive patients was significantly higher (p < 0.001). CONCLUSION: Overall, these results can be of additional benefit for clinical applications, in comparison to the ProMisE classification method. In addition, PR, ER, vascular infiltration, hyperlipidemia and atherosclerosis were found to be the key factors affecting EC prognosis.

Second primary malignancies after ovarian cancer: A SEER-based analysis (1975-2016).

OBJECTIVE: To investigate the risk of occurrence of second primary malignancies (SPMs) in survivors of ovarian cancer (OC) using large data from the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Multiple primaries standardized incidence ratios (MP-SIRs) to calculate the risk of developing second primary malignancies after a diagnosis of ovarian cancer. RESULTS: Of our included 59,880 women with OC, 3972 cases (6.6%) developed 4495 s primary malignancies over an average follow-up period of 114.39 (±102.66) months. Overall, the risk of occurrence of second primary malignancies after a diagnosis of OC was greater than what would be expected for a reference US population (SIR = 1.05, 95%CI = 1.02-1.08, p-value < 0.05). The occurrence of second myeloid malignancies and second thyroid cancer were most notable across our latency periods. Among the most significant second primary malignancies by latency were malignancies of the appendix (SIR = 14.04, 95%CI = 5.65-28.93, p-value <0.05) at 2-11 months, the small intestine (SIR = 3.15, 95%CI = 1.76-5.2, p-value <0.05) at 12-59 months, and the urinary bladder (SIR = 1.63, 95%CI = 1.3-2.02, p-value <0.05) after 10 years of an OC diagnosis. CONCLUSION: Women with OC are at significant risk for the development of second primary malignancies across all sites, as compared to a reference US population, and may benefit from second primary malignancies site-specific screening post-diagnosis.

Screening and identification of Lynch syndrome: a systematic review of the frequency of Lynch syndrome-associated clinicopathologic and molecular characteristics in Lynch syndrome gynecologic cancers.

BACKGROUND: This study aimed to investigate the frequency of Lynch syndrome-associated clinicopathologic and molecular characteristics in Lynch syndrome gynecologic cancers. METHODS: A systematic literature search was conducted in the literature databases (Medline, CINAHL, EMBASE, Google Scholar, Cochrane Library, and Clinicaltrials.gov) to identify the studies describing clinicopathologic characteristics, MMR protein immunohistochemistry and/or MSI, MLH1 methylation, and genetic testing in Lynch syndrome gynecologic cancer patients. RESULTS: A total of 24 of the evaluated studies that met the inclusion criteria were identified. A clinicopathological examination confirmed 242 endometrial cancer, 17 clear cells endometrial cancer, 35 serous endometrial cancer, 30 mixed and 21 other endometrial cancer. Thus, a total of 345 endometrial cancer was confirmed from the screening of 1,317 gynaecological cancer. However, the morphological analysis demonstrated 236 patients with endometrial cancer associated with Lynch syndrome. The frequency of confirmed LS with endometrial cancer was 68.40%. At diagnosis, the median age was 49.94±4.34 years, and the average BMI was 26.07±3.77 kg/m2. Endometrioid histology and stage I disease were the most frequent at 70.97% and 71.19% histological type and FIGO stage, respectively. Similarly, morphological and histological analysis demonstrated a higher degree of grade I cancer (47.28) and lymphovascular invasion (56.52%), respectively. DISCUSSION: Lynch syndrome-associated clinicopathologic and molecular characteristics occur significantly in Lynch syndrome gynecologic cancers and may improve risk stratification and triaging of gynecologic cancers for genetic testing.

Prebiotic Maltose Gel Can Promote the Vaginal Microbiota From BV-Related Bacteria Dominant to Lactobacillus in Rhesus Macaque.

The high incidence of bacterial vaginosis recurrence is common after treatment with an antibiotic agent and suggests the need for new treatments to prevent this. We conducted a randomized trial to evaluate the ability of maltose gel to treat bacterial vaginosis. Eighteen female rhesus macaques were randomly assigned, in a 2:1 ratio, to receive maltose gel or placebo gel by syringe to the fornix of the vagina for five consecutive days. We used 16S rRNA sequencing data from 70 swab samples of vaginal secretions in two groups in total on days 0, 3, and 5 after medication initiation and days 3 and 5 after medication withdrawal for the study of microbiome composition. We found that, in the placebo control group, there was no significant change in the composition and abundance of vaginal microbiota during the follow-up period. In the maltose gel test group, the abundance of Lactobacillus in the vagina microbiota increased gradually with the prolongation of the treatment time on Days 3 and 5 (ANOVA p = 6.99e-5 < 0.01) but began to decrease after the withdrawal of maltose gel, which was different from that of the control group. Correspondingly, the diversity and abundance of BV-related bacteria, Fusobacterium, Parvimonas, Mobiluncus, Campylobacter, Prevotella, and Sneathia, decreased on Day 0 to Day 5 of medication and increased after drug withdrawal in the maltose gel test group. The study confirms that maltose gel can facilitate the proliferation of Lactobacillus and promote the transition of the vaginal microbiota from BV-related bacteria dominant to Lactobacillus dominant in the rhesus macaque.

Vaginal microbiome analysis of healthy women during different periods of gestation.

To assess the vaginal microbiome throughout full-term uncomplicated pregnancy, a longitudinal study was designed for 12 healthy women who had prepared to become pregnant and then delivered at term (38-42 weeks) without complications. The vaginal microbial community was studied at pre-pregnancy, 8-12, 24-28, 37-38 weeks of gestation, and puerperium, using hypervariable tag sequencing of the V3-V4 region of the 16S rRNA gene. Sequencing produced approximately 10 million reads on the Illumina MiSeq. Members of the Firmicutes phyla were prevailing before and during pregnancy periods, and the proportion was quite as Proteobacteria until puerperium. Lactobacillus genus was abundant before and during pregnancy, but post-delivery vaginal microflora variety turned diverse. The species-level analysis revealed that a healthy vaginal microbiome before or during pregnancy was prominently dominated by Lactobacillus crispatus. Furthermore, PCoA analysis revealed for differences in the bacterial community composition between the two levels of Lactobacillus species in pre-pregnancy and pregnancy period (PC1 contribution of 58.46%, PC3 contribution of 8.64%). Based on the taxonomic and PCoA analysis, we found that L. crispatus was dominant in the vaginal microflora of healthy women before or during pregnancy, but at the puerperium, the status changed leading to decreased abundance of protective Lactobacillus species that made vaginal micro-ecological barrier vulnerable to diseases. Additionally, vaginal pH was an important environmental property affecting the vaginal microbial community.

Biofilms of vaginal Lactobacillus in vitro test.

This paper focuses on biofilms of Lactobacillus spp. - a type of normal flora isolated from healthy human vaginas of women of childbearing age; thereupon, it broadens the research scope of investigation of vaginal normal flora. The static slide culture method was adopted to foster biofilms, marked by specific fluorescence staining. Laser scanning confocal and scanning electron microscopy were used to observe the microstructure of the biofilms. Photographs taken from the microstructure were analysed to calculate the density of the biofilms. The body of Lactobacillus spp., though red, turned yellow when interacting with the green extracellular polysaccharides. The structure of the biofilm and aquaporin within the biofilm were imaged. Lactobacillus density increases over time. This study provides convincing evidence that Lactobacillus can form biofilms and grow over time in vitro. This finding establishes an important and necessary condition for selecting proper strains for the pharmaceutics of vaginal ecology.

Role of Liquid-based Cytology and Cell Block in the Diagnosis of Endometrial Lesions.

BACKGROUND: Liquid-based cytology (LBC) offers an alternative method to biopsy in screening endometrial cancer. Cell block (CB), prepared by collecting residual cytological specimen, represents a novel method to supplement the diagnosis of endometrial cytology. This study aimed to compare the specimen adequacy and diagnostic accuracy of LBC and CB in the diagnosis of endometrial lesions. METHODS: A total of 198 women with high risks of endometrial carcinoma (EC) from May 2014 to April 2015 were enrolled in this study. The cytological specimens were collected by the endometrial sampler (SAP-1) followed by histopathologic evaluation of dilatation and curettage or biopsy guided by hysteroscopy. The residual cytological specimens were processed into paraffin-embedded CB after LBC preparation. Diagnostic accuracies of LBC and CB for detecting endometrial lesions were correlated with histological diagnoses. Chi-square test was used to compare the specimen adequacies of LBC and CB. RESULTS: The specimen inadequate rate of CB was significantly higher than that of LBC (22.2% versus 7.1%, P < 0.01). There were 144 cases with adequate specimens for LBC and CB preparation. Among them, 29 cases were atypical endometrial hyperplasia (11 cases) or carcinoma (18 cases) confirmed by histology evaluation. Taking atypical hyperplasia and carcinoma as positive, the diagnostic accuracy of CB was 95.1% while it was 93.8% in LBC. When combined LBC with CB, the diagnostic accuracy was improved to 95.8%, with a sensitivity of 89.7% and specificity of 97.4%. CONCLUSIONS: CB is a feasible and reproducible adjuvant method for screening endometrial lesions. A combination of CB and LBC can improve the diagnostic accuracy of endometrial lesions.

Liquid-based endometrial cytology associated with curettage in the investigation of endometrial carcinoma in postmenopausal women.

OBJECTIVE: The aim of this study was to investigate the diagnostic accuracy of liquid-based endometrial cytology in postmenopausal women, in comparison with histology. MATERIALS AND METHODS: There were 790 postmenopausal women scheduled for hysteroscopy enrolled in this study. After providing informed consent, all patients proceeded sequentially through endometrial cytology, hysteroscopy, and then dilatation and curettage (D&C). Cytology sampling was performed by brushing the uterus cavity using SAP-1 and the sample was prepared to liquid-based smear using SurePath technology. The slides were stained by Papanicolaou method. All cytological diagnoses were correlated with the D&C histological diagnoses. RESULTS: Cytohistological correlations were possible in 567 (71.8%) patients: the D&C was inadequate in 204 (25.8%) patients; the cytology was inadequate in 32 (4.1%) patients; and both were inadequate in 13 (1.6%) patients. SAP-1 provided more sufficient material for cytology than D&C can for histology (p < 0.001). Taking atypical hyperplasia and endometrial carcinoma as a positive result, the diagnostic accuracy of liquid-based endometrial cytology was 81.5%; sensitivity was estimated at 75.9%, specificity at 83.3%, positive predictive value at 59.1% and negative predictive value at 91.6%. CONCLUSION: Liquid-based endometrial cytology can be considered a useful method in the detection of endometrial pathology in postmenopausal women.

[Sucrose gel for treatment of bacterial vaginosis: a randomized, double-blind, multi-center, parallel-group, phase III clinical trial].

OBJECTIVE: To evaluate the cure effectiveness and safety of sucrose gel in the treatment of bacterial vaginosis through a multi-center, randomized, double-blind, parallel controlled clinical study. METHODS: A clinical research method of multi-center, randomly double-blind, and dose group parallel comparison was adopted. In the study, 533 patients with bacterial vaginosis were randomly divided into two groups, which included 214 cases in the control group (5.0 g metronidazole gel) and 319 cases in the trial group (5.0 g sucrose gel ). The patients were treated with different medication according to the group where they were. All the cases in these two groups were treated with drugs vaginally twice in a day, morning and evening separately, for 5 days. The curative effect and safety evaluation were assessed from 7 to 10 days and 21 to 30 days after treatment respectively. RESULTS: The efficacy of the comprehensive clinical treatment showed that the cure rate of metronidazole gel group and sucrose gel group were 70.53% and 80.83% respectively 7 to 10 days after treatment. The recovery rate of Nugent score for vaginal smear were 71.50% and 81.15% respectively. The differences in the efficacy between these two groups were significant statistically (P<0.05). However, the cure rates of metronidazole gel group and sucrose gel group were 63.29% and 61.98% respectively 21 to 30 days after treatment. No statistically significant difference (P>0.05) could be found in the cure rates of the two groups. CONCLUSION: The clinical comprehensive efficacy and recovery of vaginal bacteria of sucrose gel group in the treatment of bacterial vaginosis were obviously superior to those of metronidazole gel 7 to 10 days after treatment. The susucrose gel could improve the clinical efficacy index and laboratory index of bacterial vaginosis. Other effects included the release of clinical symptoms, and the recovery of the normal micro-environment in the vagina according to the Nugent score. The curative efficacy of sucrose gel was equal to that of metronidazole gel 21 to 30 days after treatment. In the future, sucrose gel treatment can be a new strategy for the treatment of bacterial vaginosis. Various advantages can be taken to improve the cure rate of bacterial vaginosis and reduce the shortcomings produced by this disease.

[Confocal laser scanning electron microscopy for assessment of vaginal Lactobacillus crispatus biofilm].

OBJECTIVE: To investigate the female vaginal Lactobacillus crispatus biofilm by using confocal laser scanning microscopy (CLSM),thus revealing the formation of biofilm. METHODS: The cover slide biofilm culture approach in vitro was employed for induction of the vaginal Lactobacillus crispatus biofilm formation. Following the culture for 2, 4, 8, 12, 16, 20, 24, 48, 72, 96 and 120 hours, the cover slide was removed for subsequent staining with the fluoresce in isothiocyanate-conjugated concanavalin A(FITC-ConA) and propidium (PI).This was followed by determination of the formation and characteristics of the vaginal Lactobacillus crispatus biofilm by using CLSM. RESULTS: The CLSM images of biofilm formation at different time points were captured, suggesting that the vaginal Lactobacillus crispatus adhesion occurred at h 4, which was in reversible attachment, then more and more Lactobacillus crispatus aggregated at h 8 to h 20, which was in irreversible attachment.Lactobacillus crispatus clustered at h 20, with early development of biofilm architecture.Then the biofilm with extracellular matrix around the bacteria was set up at h 24,with gradual matureation at h 24 to h 48.The biofilm dispersed at h 72. The biofilm density of cultivating for 20 hours was 42.7 × 10⁻³ ± 6.8 × 10⁻³ ,and for 24 hours increased to 102.5 × 10⁻³ ± 23.1 × 10⁻³, suggesting a significant difference, P<0.05. This meant that mature biofilm was formed at h 24. CONCLUSION: The vaginal Lactobacillus crispatus is able to form typical biofilm with distinct developmental phases and architecture characteristics.Mature biofilm is formed at h 24 to h 48, then the biofilm begins to disperse.

Combining endometrium sampling device and SurePath preparation to screen for endometrial carcinoma: a validation study.

BACKGROUND: The aim of this study was to compare specimen adequacy of SAP-1 provided for cytology with that of dilation and curettage (D & C) or hysteroscopy for histology, and evaluate the accuracy of combining endometrium sampling by SAP-1 and liquid-based cytology using SurePath preparation for screening endometrial carcinoma and its precursor. METHODS: Endometrial specimens from women (n = 1514) with risk factors were obtained using an SAP-1 device for cytological analysis; histological samples were obtained from 375 of these women who underwent D & C or hysteroscopy. Cytological specimens were prepared to liquid-based smear using SurePath technology and stained by Papanicolaou. Histological samples were processed in routine pathology and stained by hematoxylin and eosin. RESULTS: Adequate specimens for cytology were obtained from 1458/1541 patients (96.3%), while adequate samples for pathology were obtained from 285/375 patients (76%). However, for postmenopausal women, 1006 of 1045 cytology (86.3%) were adequate, 153 of 238 histology (64.3%) were adequate, it was easier to collect cytological specimens than histological specimens (P < 0.05). The accuracy of endometrial cytology for detecting endometrial carcinoma and its precursor was 92.4% (sensitivity, 73%; specificity, 95.8%; positive predictive value, 75%; and negative predictive value, 95.3%). CONCLUSIONS: Endometrial cytology using SAP-1 sampling and SurePath preparation may be a reliable approach for screening patients with endometrial carcinoma and its precursor.

Relationship between the expressions of mitofusin-2 and procollagen in uterosacral ligament fibroblasts of postmenopausal patients with pelvic organ prolapse.

OBJECTIVES: To compare the mRNA and protein expressions of mitochondrial fusion protein-2 (mitofusin-2, Mfn2), and procollagen 1A1/1A2/3A1 in uterosacral ligament fibroblasts of postmenopausal patients with or without pelvic organ prolapse (POP). The effect of Mfn2 on the expression of procollagen in fibroblasts was also investigated. STUDY DESIGN: Thirty-seven POP patients and 23 non-POP postmenopausal patients were included in the POP (study) and non-POP (control) groups, respectively. Laser capture microdissection (LCM) was combined with quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting to detect the mRNA and protein expressions of Mfn2, and types I and III procollagen in uterosacral ligament fibroblasts of the two groups, and the differences in expression levels were compared between the groups. The correlation between Mfn2 and procollagens was also investigated. RESULTS: Fibroblasts were successfully isolated from frozen sections of the uterosacral ligament using LCM. The results of qRT-PCR and western blot showed that the expressions of types I and III procollagen were significantly lower and those of Mfn2 were significantly higher in the POP group than in the non-POP group (p<0.05, all). In POP, opposite trends of protein expression changes of Mfn2 and procollagens were observed along with the duration of postmenopause (P<0.05), while this was not the case in POP accompanied by stress urinary incontinence and frequency of vaginal delivery (P>0.05). The expressions of type I and III procollagen were negatively associated with Mfn2 in POP patients (-1

[Efficacy of postoperative simple chemotherapy and concurrent chemoradiotherapy in FIGO stage IB2-IIB cervical cancer].

OBJECTIVE: To evaluate the effectiveness of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy plus postoperative chemotherapy but no radiotherapy for stage IB2-IIB cervical cancer. METHODS: Seventy-nine patients with stage IB2-IIB cervical cancer were treated with NAC followed by radical hysterectomy. According to different adjuvant therapies, patients were divided into postoperative chemotherapy group (47 cases) and postoperative radiotherapy/concurrent chemoradiotherapy group (32 cases). Regimens for NAC and postoperative chemotherapy were BIP (bleomycin+ ifosfamide+ cisplatin/carboplatin) or TP (paclitaxel+ cisplatin/carboplatin). An average of 1.1±0.3 cycles of NAC and 3.4±1.2 cycles of postoperative chemotherapy were prescribed. RESULTS: Toxicities due to chemotherapy were generally tolerable. Overall response rate of NAC was 88.6%. With a median follow-up period of 42 months, the three-year progression-free survival rates of the two groups were 88.5% and 84.3%, the total survival rates were 90.3% and 86.4%, respectively. There was no statistically significant difference. The recurrent rates were 10.6% and 21.8% in the two groups. In the absence of radiotherapy, pelvic recurrence was observed in two patients; the other three had distant metastases. CONCLUSION: The results indicate that NAC followed by surgery plus postoperative chemotherapy but no radiotherapy offers a viable option in the treatment of stage IB2-IIB cervical cancer. The patients can tolerate the side effects of chemotherapy with better efficacy.

RNA interference-mediated targeting of DKK1 gene expression in Ishikawa endometrial carcinoma cells causes increased tumor cell invasion and migration.

The Wnt signaling pathway plays an essential role in tumor invasion and migration. DKK1 functions as an important inhibitor of the pathway and represents a promising target for cancer therapy. The aim of the present study was to determine the role of DKK1 in endometrial carcinoma (EC) cell invasion and migration using RNA interference (RNAi) technology. Ishikawa EC cells were transfected at high efficiency with specific DKK1 siRNA. RT-PCR and western blot analysis were used to determine the mRNA and protein levels of DKK1, ß-catenin and metalloproteinase 14 (MMP14) in siRNA-treated and -untreated cells. In addition, the invasion and migration of the EC cells were detected by invasion and migration assays. Transient transfection of DKK1 siRNA significantly inhibited the mRNA and protein levels of DKK1. Markedly increased cell invasion and migration was observed following treatment with DKK1 siRNA when compared with the negative control siRNA-treated and siRNA-untreated cells. The knockdown of DKK1 also elevated the mRNA and protein levels of ß-catenin and MMP14 involved in the Wnt signaling pathway, indicating that targeting this gene may promote intracellular Wnt signal transduction and thus, accelerate EC cell invasion and migration in vitro. The RNAi-mediated targeting of DKK1 gene expression in Ishikawa EC cells resulted in increased tumor cell invasion and migration. DKK1 was identified as an inhibitor of EC cell invasion and migration via its novel role in the Wnt signaling pathway. Targeting DKK1 may therefore represent an effective anti-invasion and -migration strategy for the treatment of EC.

[Screening and sampling of endometrial carcinoma accuracy of the endometrial cytology test for the screening of endometrial cancer].

OBJECTIVE: To evaluate the accuracy of endometrial cytology test (ECT) for the diagnosis of endometrial cancer or precancerous lesions and then discuss the value of ECT as a screening tool for endometrial cancer.Secondly, to investigate related characteristics and independent risk factors of epidemiology of endometrial carcinomas and atypical endometrial hyperplasia to advise proper crowd for endometrial carcinomas screening and monitoring. METHODS: Totally 1717 preoperative questionnaires on hysteroscopy + dilation & curettage, histopathology and endometrial cytological tests in Peking University First Hospital, People's Hospital of Beijing Daxing District and Beijing Cancer Hospital, from March 2009 to May 2013 were completed. Histopathologic diagnoses were used as the gold standard for determining the accuracy of ECT.Extrapolation: applied binary logistic regression method to narrow down the risk factors of histopathology and endometrial cytological examination. RESULTS: Satisfaction rate of cytological specimens and pathological specimens were 96.45% (1656/1717) and 91.44% (1570/1717), respectively. ECT provided sufficient material for the diagnosis significantly more often than histopathology (P < 0.05). For the ECT diagnosis of endometrial cancer: accuracy was estimated at 88.2%, sensitivity at 87.3%, specificity at 88.3%, positive predictive value (PPV) at 41.9%, negative predictive value (NPV)at 98.6%.Univariate analysis revealed that risk factors of diagnosis of endometrial carcinomas and atypical hyperplasia of histopathology were included:body mass index (BMI) ≥ 25 kg/m(2), age ≥ 40 years old, diabetes mellitus, hypertension, menopause, family history of malignant tumor (all P < 0.10). Multifactor analysis revealed that the independent risk factors were included:BMI ≥ 25 kg/m(2), age ≥ 40 years, menopause and family history of malignant tumor (all P < 0.05). CONCLUSIONS: The results of the current study indicated that the accuracy of ECT for the diagnosis of endometrial cancer was high.Furthermore, ECT could be a useful tool for the screening of endometrial cancer.Independent risk factors of endometrial carcinomas and atypical endometrial hyperplasia including:age over 40 years, BMI ≥ 25 kg/m(2), menopause and family history of malignant tumor.

[Results of different postoperative adjuvant therapies for stage Ib-IIa cervical carcinoma with risk factors].

OBJECTIVE: To investigate the effects of postoperative adjuvant chemotherapy (CT) and chemoradiotherapy (CRT) or radiotherapy(RT) for Ib-IIa cervical cancer with risk factors. METHODS: From March 1995 to June 2010, there were 137 patients underwent radical hysterectomy and systematic pelvic lymphadenectomy for stage Ib-IIa cervical cancer admitted at Peking University First Hospital. These patients had risk factors, intermediate risk factors including bulky tumor ( > 4 cm) , lymph vascular space invasion, deep stromal invasion; high risk factors including positive surgical margin, parametrial invasion, lymph node involvement. Of the all patients, 79 cases of them were treated with CT, 58 of them were treated with RT or CRT. The 5-year survival and prognosis factors were analyzed retrospectively, the prognosis was compared between two adjuvant therapy groups. RESULTS: The univariate analysis shown that types of pathology, different grade of risk factors, stroma invasion and lymph node involvement were prognostic factors of 5-year overall survival. Patients with squamous cell carcinoma, intermediate risk factors, no parametrial invasion, and no lymph node involvement had better prognosis(P < 0.05). Whether patients with high-risk factors or intermediate-risk factors, the 5-year overall survival and 3-year disease-free survival had no difference between CT and RCT or RT groups respectively. Cox regression multivariate analysis of survival indicated that clinical stages, types of histology, different grade of risk factors were independent prognostic indicator. Patients with early stage, squamous cell carcinoma, intermediate risk factors had better prognosis. Univariate and multivariate analysis indicated that different postoperative adjuvant therapies had no effects on the prognosis. The 5-year overall survival was 88.6% in patients treated with CT, and 89.7% in patients treated with RT or CRT (P = 0.455) . CONCLUSION: There are equivalent therapeutic results between CT and RT or CRT for patients with risk factors after radical surgery, CT may be as one choice of postoperative adjuvant therapy for stage Ib-IIa cervical carcinoma with risk factors.

[Methylation of matrix metalloproteinases-2 promoter in endometrial cancer invasion].

OBJECTIVE: To investigate the regulation of DNA methylation on the expression of MMP-2 gene, and the effect of 5-aza-2'-deoxycytidine (5-aza-CdR) on invasiveness of endometrial cancer cells. METHODS: Human endometrial cancer cell lines Ishikawa and HEC-1A were treated with 5-aza-CdR. After genomic DNA was extracted from the cells and treated with bisulfate sodium, clone sequencing was used to detect methylation of the matrix metalloproteinases-2 (MMP-2) promoter region. Ishikawa and HEC-1A cells were treated with different concentrations of 5-aza-CdR, and the effect on the invasion and metastasis to the endometrial cancer (EC) cells were detected by Transwell invasion chamber. The MMP-2 mRNA expression was detected by real-time quantitative PCR. RESULTS: Although the MMP-2 promoter showed global hypomethylation status, the methylation of CG dinucleotide sites located on the transcription factor binding sites had high positive frequencies, which were 80% and 70% in HEC-1A cells and 60% and 40% in Ishikawa cells, respectively. The methylation frequencies reduced to 20% and 10% in HEC-1A cells by demethylating agent 5-aza-CdR and the CG sites in Ishikawa cells were totally demethylated. Moreover, after 72 h of treatment with different concentrations of 5-aza-CdR, the expression of the MMP-2 mRNA and transmembrane number of both Ishikawa and HEC-1A cells were significantly upregulated compared with the control group (P<0.05). CONCLUSION: Methylation of CG dinucleotide sites of the MMP-2 promotor region may be associated with the regulation of gene transcription. The 5-aza-CdR can promote the invasion and metastasis of endometrial cancer cells in vitro by upregulating the MMP-2 mRNA expression.

[Effect of Ras signal regulating Cox7a2 expression and its sub-cellular location in testicular interstitial cell].

OBJECTIVE: To investigate the co-sub-cellular-location of Cox7a2 and Ras. METHODS: Ras and its mutant plasmid were cloned by RT-PCR and sequence analysis. Cox7a2-pEYFP-N1, Ras-pEYFP-N1 and N17-Ras-pEYFP-N1 fluorescent protein vectors were constructed and transfected into TM3 cells. RESULTS: Cox7a2 was located in the mitochondria, but its location was changed by the expression of Ras. When the dominant negative ras was expressed in the cells, the Cox7a2 located into the mitochondria again. CONCLUSION: Cox7a2 mediated testosterone production, which might be at least in part related with the Ras signaling pathway. Ras may be the regulating target and further investigation is needed to make it clear.

High levels of activin A detected in preeclamptic placenta induce trophoblast cell apoptosis by promoting nodal signaling.

CONTEXT: The pregnancy-specific disorder preeclampsia is a major cause of maternal mortality and morbidity. Activin A has been suggested as a potential biomarker of the disease, but whether it plays a role in the pathology of preeclampsia or is just a manifestation of the disease is not fully understood. OBJECTIVE: The objective of the study was to examine the roles of Activin A on placental trophoblast cells under pathological conditions of preeclampsia. DESIGN: Placental and plasma productions of Activin A in healthy pregnant women and preeclamptic patients were compared by using clinical samples obtained from Peking University First Hospital during November 2005 to November 2007. The role of Activin A at pathological doses was investigated in human trophoblast cells. RESULTS: Plasma and placental productions of Activin A were significantly higher in preeclamptic patients when compared with normal pregnant subjects in a Chinese Han population. Treatment of trophoblast cells with high doses of Activin A resulted in a significant increase in cell apoptosis. This effect was blocked not only by silencing Activin A's receptor activin receptor-like kinase 4 but also by knockdown of Nodal's receptor ALK7. Important to note was that Activin A could significantly increase Nodal expression in trophoblast cells, and knockdown of Nodal resulted in evident blockage on Activin A-induced trophoblast cell apoptosis. CONCLUSION: High levels of Activin A observed in preeclamptic placenta may play a role in the pathogenesis of preeclampsia by inducing excessive apoptosis in placenta indirectly through enhancing Nodal expression.