Weiguo Lv

Reduced miR-34a expression in normal cervical tissues and cervical lesions with high-risk human papillomavirus infection.

Introduction: Reduced miR-34a expression is associated with high-risk human papillomavirus (HR-HPV) infection and cervical cancer. Whether the reduction of miR-34a expression induced by HR-HPV E6 occurs in precancerous lesions, even before morphologic change, is still uncertain. Our study aimed to ascertain the possibility of pri-miR-34a involved in the development of cervical lesions and to explore the mechanism of altered pri-miR-34a expression induced by HPV-16 E6. Methods: The levels of pri-miR-34a expression were examined in different cervical tissues, including normal cervical epithelium with (n = 32) or without (n = 32) HR-HPV infection, cervical intraepithelial neoplasia (CIN) with (n = 32) or without (n = 12) HR-HPV infection, and cervical cancer (n = 32), by semiquantitative reverse transcription-polymerase chain reaction. The HPV-16 E6 expression vector and HPV-16 E6 small interfering RNAs were conducted and transfected into 293T cells and SiHa cells, respectively. The expression of pri-miR-34a and p53 protein was simultaneously analyzed by reverse transcription-polymerase chain reaction and Western blot in cells with gene transfection and without. Results: pri-miR-34a expression was significantly reduced in CIN and cervical cancer compared with normal cervical epithelium, as well as in CIN 2 and CIN 3 compared with CIN I. Moreover, the expression of pri-miR-34a was significantly lower in normal cervical epithelium and CIN with HR-HPV infection than in those without. Simultaneous down-regulation or up-regulation of pri-miR-34a and p53 expression was observed in E6-transfected 293T cells or E6 small interfering RNA-transferred SiHa cells compared with controls. Conclusions: Reduced expression of pri-miR-34a occurs not only in cervical cancer but also in precancerous lesion even before morphologic change. The inhibition of miR-34a expression induced by HR-HPV E6 in the p53-dependent pathway is probably an early-onset event in the development of cervical cancer.

Outcomes of conservative therapy for young women with early endometrial adenocarcinoma

Four of six patients with endometrial cancer had initial response to progesterone therapy and obtained complete response; three among them had successful pregnancies with three live births. The results suggest that progesterone therapy, combined with assisted reproductive technology, provides more chance of carrying a full-term pregnancy for patients with endometrial adenocarcinoma.

Relapsed or refractory gestational trophoblastic neoplasia treated with the etoposide and cisplatin/etoposide, methotrexate, and actinomycin D (EP-EMA) regimen

Objective To evaluate the effectiveness of the etoposide and cisplatin/etoposide, methotrexate and actinomycin D (EP‐EMA) regimen in patients with gestational trophoblastic neoplasia who had been successfully treated with the etoposide, methotrexate, and actinomycin D/cyclophosphamide and vincristine (EMA‐CO) regimen but experienced a relapse, or who became refractory to EMA−CO treatment. Methods From January 1999 to December 2005, 18 patients with gestational trophoblastic neoplasia who had been successfully treated with the EMA‐CO regimen but sustained a relapse (n = 7) or who became refractory to it (n = 11) were treated with the EP‐EMA regimen. The effectiveness, adverse effects, and tolerated dose intensity of the EP‐EMA regimen were retrospectively analyzed. Results The 18 patients received a total of 74 cycles of the EP‐EMA regimen and 12 (66.7%) achieved complete remission. Nine of the 11 patients (81.8%) apparently resistant to the EMA‐CO regimen achieved complete remission. However, only 3 of the 7 patients (42.9%) who experienced a relapse after treatment with the EMA‐CO regimen achieved complete remission. The main adverse effects of the EP‐EMA regimen were myelosuppression and gastrointestinal problems. Because of myelosuppression and hepatotoxicity, only 56.8% of the patients could be treated with the planned dose intensity. Conclusion EP‐EMA may be an effective option for the treatment of gestational trophoblastic neoplasia in patients resistant to treatment with the EMA‐CO regimen. However, it does not seem to benefit all the patients who experienced a relapse after treatment with the EMA‐CO regimen.

Changes in Prevalence and Clinical Characteristics of Cervical Cancer in the People's Republic of China: A Study of 10,012 Cases From a Nationwide Working Group

PURPOSE About one-third of the worlds total annual new cervical cancer cases are found in the Peoples Republic of China. We investigate the prevalence and clinical characteristics of cervical cancer cases in the Peoples Republic of China over the past decade. METHOD A total of 10,012 hospitalized patients with cervical cancer from regions nationwide were enrolled from 2000 to 2009. Demographic and clinical characteristics, therapeutic strategies, and outcomes were analyzed. RESULTS The mean age at diagnosis of all cervical cancer patients was 44.7 ± 9.5 years, which is 5-10 years younger than mean ages reported before 2000 in the Peoples Republic of China. The age distribution showed 16.0% of patients were ≤35 years old, 41.7% were 35-45 years old, and 41.7% were >45 years old. Early stage diagnoses were most prevalent: 57.3% were stage I, 33.9% were stage II, and 4.3% were stage III or IV. Most patients (83.9%) were treated with surgery, and only 9.5% had radiotherapy alone. Among 8,405 patients treated with surgery, 68.6% received adjuvant treatments, including chemotherapy (20.9%), radiotherapy (26.0%), and chemoradiotherapy (21.9%). Among stage IA patients, 16.0% were treated with corpus uteri preservation. The proportion of ovarian preservation was 42.0%. CONCLUSIONS Cervical cancer cases in the Peoples Republic of China show increasing prevalence in young patients and at early stages. In the past 10 years, surgery has become the dominant treatment and is increasingly combined with adjuvant chemotherapy for patients with stages I and II. Conservative surgical approaches are reasonable options for genital organ preservation in selected patients.

Matched-case comparison of neoadjuvant chemotherapy in patients with FIGO stage IB1-IIB cervical cancer to establish selection criteria.

OBJECTIVE Neoadjuvant chemotherapy (NACT) for cervical cancer still remains controversial. NACT was evaluated to establish selection criteria. METHODS A matched-case comparison was designed for the NACT group (n=707) and primary surgery treatment (PST; n=707) group to investigate short-term responses and high/intermediate risk factors (HRFs/IRFs). The 5-year disease-free survival (DFS) and overall survival (OS) rates were stratified by NACT response, HRFs/IRFs, International Federation of Gynecology and Obstetrics (FIGO) stage and tumour size, respectively. RESULTS The clinical and pathological response rates were 79.3% and 14.9% in the NACT group. In comparison to the PST group, IRFs but not HRFs were significantly decreased (P<0.05), and the 5-year DFS rate was significantly improved in the NACT group (88.4% versus 83.1%, P=0.021). Moreover, the 5-year DFS and OS rates were favourably increased in the clinical responders in comparison to the PST group and the clinical non-responders (P<0.05). Compared to those of clinical non-responders, the 5-year DFS and OS rates of clinical responders, with or without HRFs, were also significantly increased (P<0.01). In stage IB2, the 5-year DFS and OS rates were significantly increased, whereas operation duration declined in the NACT group (P<0.05). For patients with stage IB tumours of 2-5 cm, the 5-year DFS and OS rates of clinical responders were significantly improved (P<0.05). CONCLUSIONS NACT is a suitable option for patients with cervical cancer, especially for NACT responders and patients with stage IB, which provides a new concept of fertility preservation for young patients.

The Expression of Interleukin-10 in Patients with Primary Ovarian Epithelial Carcinoma and in Ovarian Carcinoma Cell Lines:

This study determined interleukin-10 (IL-10) expression in patients with ovarian carcinoma and in ovarian carcinoma cell lines, and investigated its clinical significance in the development and progression of ovarian carcinoma. Expression of IL-10 in ovarian carcinoma, benign ovarian tumour, normal control tissues and ovarian carcinoma cell lines was detected by immunohistochemistry and Western blot analysis. IL-10 concentrations in sera and ascites from patients with ovarian carcinoma, in sera from patients with benign ovarian tumour and normal controls, and in supernatants of ovarian carcinoma cell line cultures were measured by enzyme-linked immunosorbent assay. The tissue level of IL-10 in ovarian carcinoma was significantly higher than in benign ovarian tumour and normal controls. IL-10 expression was detectable in cell lysate and supernatant from ovarian carcinoma cell lines. In patients with ovarian carcinoma the IL-10 level in ascitic fluid was significantly higher than in sera, and the serum IL-10 level in ovarian carcinoma was significantly higher than in benign ovarian tumour and normal controls. Ascitic IL-10 levels in ovarian carcinoma were significantly correlated with disease stage but not cytological grade. These results suggest that ovarian carcinoma cells are able to synthesize and secrete IL-10, which probably assists in promoting the development and progression of ovarian carcinoma.

Factors associated with positive margins in patients with cervical intraepithelial neoplasia grade 3 and postconization management

To evaluate the risk factors for positive margins in cervical intraepithelial neoplasia (CIN) grade 3 and the outcomes of postconization management.

Evaluation of the accuracy of intra-operative gross examination for the surgical management of endometrial cancer

OBJECTIVE The aim of this study was to explore the clinical value of intra-operative gross examination for the surgical management of endometrial carcinoma. STUDY DESIGN A retrospective study was conducted in 424 women who underwent surgical treatment for endometrial carcinoma between January 2002 and December 2006. The results of myometrial invasion and cervical infiltration as assessed by intra-operative gross examination were compared with the final microscopic histopathological results in 401 patients. The accuracy, sensitivity, and specificity were calculated. Chi-squared or Fishers exact tests were used for the comparison of categorical variables. RESULTS Intra-operative gross examination correctly identified the depth of microscopic myometrial invasion in 90.3% of patients. The sensitivity in detecting myometrial invasion was 80.6% and the specificity was 92.4%. With regard to cervical involvement, gross examination had an overall accuracy of 84.3%. The sensitivity in detecting cervical involvement was 32.6% and the specificity was 99.0%. Usually, cervical involvement cannot be correctly identified by intra-operative gross examination in patients with diffuse foci. CONCLUSION The data suggest that intra-operative gross examination is a simple and good method of predicting myometrial invasion, but it may not be the ideal way to assess cervical involvement in endometrial carcinoma.

Methotrexate induces apoptosis of human choriocarcinoma cell line JAR via a mitochondrial pathway

OBJECTIVE To investigate methotrexate (MTX)-induced apoptosis and the involved pathways in human choriocarcinoma cells. STUDY DESIGN MTX-induced apoptosis of human choriocarcinoma cell line JAR was examined using a PI/Annexin V stain with flow cytometer (FCM). Mitochondrial apoptosis was detected by fluorescence microscopy, and analyzed by FCM using a MitoCapture mitochondrial apoptosis detection kit. The activities of caspase-8 and caspase-9 were quantified by microtiter plate reader at 405 nm using FLICE/Caspase-8 colorimetric assay kit and Caspase-9/Mch6 colorimetric assay kit. The changes in Bax and Bcl-2 expression were detected during apoptosis using immunocytochemistry and Western blot analysis. RESULTS JAR cells underwent apoptosis after exposure to 0.1-2.5 microg/ml MTX for 48 h. Decreased mitochondrial membrane potential was observed both by fluorescence microscopy and FCM. The activation of caspase-9 was increased 4.35+/-0.76-fold in MTX-incubated JAR, while there was no obvious change in the activation of caspase-8. When JAR cells underwent apoptosis, the expression of Bcl-2 was decreased and the expression of Bax was increased; both were detected by immunocytochemistry assay. CONCLUSION Methotrexate in lower concentrations induces apoptosis of human choriocarcinoma cells via mitochondrial-initiated pathways, including reduction of mitochondrial membrane potential, activation of caspase-9, and up-regulation of Bax/Bcl-2 expression.

Expression of E-, P- and N-Cadherin and Its Clinical Significance in Cervical Squamous Cell Carcinoma and Precancerous Lesions

Aberrant expression of classical cadherins has been observed in tumor invasion and metastasis, but its involvement in cervical carcinogenesis and cancer progression is not clear. We investigated E-, P- and N-cadherin expression and its significance in cervical squamous cell carcinoma (SCC) and cervical intraepithelial neoplasia (CIN). This retrospective study enrolled 508 patients admitted to Womens Hospital, School of Medicine, Zhejiang University with cervical lesions between January 2006 and December 2010. Immunochemical staining was performed in 98 samples of normal cervical epithelium (NC), 283 of CIN, and 127 of early-stage SCC. The association of cadherin staining with clinical characteristics and survival of the patients was evaluated by univariate and multivariate analysis. We found gradients of decreasing E-cadherin expression and increasing P-cadherin expression from NC through CIN to SCC. Aberrant E-cadherin and P-cadherin expression were significantly associated with clinical parameters indicating poor prognosis and shorter patient survival. Interestingly, we found very low levels of positive N-cadherin expression in CIN and SCC tissues that were not related to CIN or cancer. Pearson chi-square tests showed that E-cadherin expression in SCC was inversely correlated with P-cadherin expression (E-P switch), and was not correlated with N-cadherin expression. More important, patients with tissues exhibiting an E-P switch in expression had highly aggressive phenotypes and poorer prognosis than those without E-P switch expression. Our findings suggest that E-cadherin and P-cadherin, but not N-cadherin staining, might be useful in diagnosing CIN and for predicting prognosis in patients with early-stage SCC.