Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

Real-world applications of PARPi maintenance therapy for recurrent ovarian cancer: A single-center study in China.

OBJECTIVE: To assess the actual clinical application of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in Chinese patients with recurrent ovarian cancer, and to explore prognostic factors associated with progression-free survival (PFS). METHODS: We retrospectively assessed real-world clinical data from our hospital using the inclusion and exclusion criteria of representative randomized controlled trials, analyzed the prognosis, and performed univariate and multivariate analyses of prognostic factors. RESULTS: Between 2019 and 2022, the proportion of platinum-sensitive recurrence ovarian cancer patients who received PARPi maintenance therapy increased to 29.6%, 53.3%, 43.8% and 62.2%, respectively, each year. A total of 48 patients were included in the prognostic analysis, of which 32 and 16 received olaparib and niraparib, respectively. Using the criteria of the Study19 and SOLO2 studies, the olaparib group in our patients had coincidence rates of 56.3% and 18.8%, respectively. Using the criteria of the NOVA and NORA studies, the niraparib group had coincidence rates of 31.3% and 37.5%, respectively. Median PFS was 26.1 months (95% CI 20.2-32.1). Response to primary therapy was an independent prognostic factor for PFS (relative risk, 3.248; 95% CI 1.081-9.757, P = 0.036). CONCLUSIONS: PARPi maintenance therapy was also effective in real world applications. Complete response (CR) to primary therapy was an independent factor favorably affecting PFS. Therefore, primary treatment choices aimed at optimal cytoreduction during primary surgery and improving the CR rate should still be considered, which positively affects the long-term prognosis of patients in the new treatment mode.

A Rare Case of Cervical Squamous Cell Carcinoma Concurrent with Sinonasal Inverted Papilloma: A Case Report.

Introduction: Cervical cancer is the fourth most common malignancy in women worldwide, and sinonasal inverted papilloma (SIP) is a rare benign sinus tumor with characteristics including a destructive growth pattern, high recurrence rate, and common malignant transformation. Cervical squamous cell carcinoma (SCC) combined with SIP has not been reported thus far. Case Presentation: A 55-year-old woman was diagnosed with cervical SCC in our center and treated with concurrent radiochemotherapy. During the follow-up period after the completion of cervical cancer treatment, the progression of cervical squamous cell carcinoma was first considered because the squamous cell carcinoma antigen (SCCA) levels remained high and slowly increased. However, SIP was found after a detailed investigation. The SCCA levels returned to normal after surgery. Two months after the surgery, because SCCA slowly increased again, it was found that the SIP recurred. After additional surgical treatment, the SCCA level returned to normal. Discussion and Conclusion: First, SCCA is an important indicator for monitoring changes in cervical SCC. When the changes in SCCA levels are inconsistent with the prognosis of cervical SCC, we should be vigilant about considering the possibility of other diseases existing at other sites in the body, which might lead to the earlier detection and treatment of SIP. Second, We recommended that SCCA be used as a routine monitoring index for SIP. If available, SCCA1 and SCCA2 should be evaluated to provide a more detailed assessment. Finally, for a high recurrence rate of SIP, anti-HPV treatment might be considered to reduce the risk of recurrence.

Cardiac safety analysis of first-line chemotherapy drug pegylated liposomal doxorubicin in ovarian cancer.

Pegylated liposomal doxorubicin (PLD) is a nano-doxorubicin anticancer agent. It was used as early as 2014 to treat ovarian and breast cancer, multiple myeloma and Kaposi's sarcoma. The 2018 National Comprehensive Cancer Network guidelines listed PLD as first-line chemotherapy for ovarian cancer. PLD has significant anticancer efficacy and good tolerance. Although PLD significantly reduces the cardiotoxicity of conventional doxorubicin, its cumulative-dose cardiotoxicity remains a clinical concern. This study summarizes the high-risk factors for PLD-induced cardiotoxicity, clinical dose thresholds, and cardiac function testing modalities. For patients with advanced, refractory, and recurrent malignant tumors, the use of PLD is still one of the most effective strategies in the absence of evidence of high risk such as cardiac dysfunction, and the lifetime treatment dose should be unlimited. Of course, they should also be comprehensively evaluated in combination with the high-risk factors of the patients themselves and indicators of cardiac function. This review can help guide better clinical use of PLD.

The impact of Pegylated liposomal doxorubicin in recurrent ovarian cancer: an updated meta-analysis of randomized clinical trials.

BACKGROUND: Previous meta-analysis studies suggested that pegylated liposomal doxorubicin (PLD) may improve the survival rate of patients with recurrent ovarian cancer. The aim of the present meta-analysis, then, was to further update the role of PLD in the treatment of recurrent ovarian cancer. METHODS: We performed a literature search using the electronic databases Medicine, EMBASE, Web of Science, and the Cochrane Library to 27 July 2020. We only restricted the randomized clinical trials. Study-specific hazard ratios and 95% confidence interval (HR/95% CI) and risk ratios and 95% confidence interval (RR/95% CI) were pooled using a random-effects model. RESULTS: Ten studies (12 trials) were included after screening 940 articles. We categorized the eligible studies into two groups: the doublet regimens (four trials, 1767 patients) showed that PLD plus carbo provided superior progression-free survival (PFS) (HR, 0.85; 95% CI, 0.74-0.97) and similar overall survival (OS) (HR, 1.00; 95% CI, 0.88-1.14) compared to paclitaxel (PAC) plus carboplatin (carbo). PLD plus carbo was associated with significantly more anemia and thrombocytopenia, and other side effects were well tolerated. The monotherapy regimens (eight trials, 1980 patients) showed that PLD possessed a similar PFS (HR, 1.02; 95% CI, 0.90-1.16) and OS (HR, 0.88; 95% CI, 0.77-1.01) relative to other monotherapies. PLD alone was also more associated with mucositis/stomatitis and hand-foot syndrome, while other side effects were well tolerated. CONCLUSIONS: In platinum-sensitive recurrent ovarian cancer, PLD plus carbo was more effective than PAC plus carbo, while in platinum-resistant or -refractory recurrent ovarian cancer, PLD exhibited similar survival to other monotherapies. Regarding side effects, PLD plus carbo and mono chemotherapy were both well tolerated.

Accuracy of transvaginal sonoelastography for differential diagnosis between malignant and benign cervical lesions: A systematic review and meta-analysis.

BACKGROUND: To evaluate the performance of transvaginal sonoelastography (TVSE) for differential diagnosis between malignant and benign cervical lesions using a meta-analysis. METHODS: An independent literature search was conducted on the English medical database, including PubMed, Embase and Medline, Cochrane Library, Web of Science, and OVID. The diagnostic accuracy of TVSE was compared with that of histopathology, which is the gold reference standard for diagnosis. The accuracy of TVSE was assessed by calculating the pooled sensitivity, specificity, diagnostic odds ratio, and area under the curve (AUC). The imaging mechanisms, assessment methods, and QUADAS scores were assessed with a meta-regression analysis. A Deeks funnel plot was performed for evaluating publication bias. RESULTS: Six eligible studies reported a total sample of 615 cervical lesions (415 cancers, 200 benign lesions). TVSE showed a pooled diagnostic odds ratio of 21.42 (95% CI 13.65-33.61), sensitivity of 0.87 (95% CI 0.84-0.90), specificity of 0.79 (95% CI 0.72-0.84), and an AUC of 0.892 (Q* = 0.822). The results of the meta-regression analysis showed that the imaging mechanism (P = .253), the assessment method (P = .279), or QUADAS score (P = .205) did not affect the study heterogeneity. CONCLUSION: TVSE has a relatively high and satisfactory value for differential diagnosis between malignant and benign cervical lesions. The diagnostic performance of strain elastography and shear wave elastography were similar and good. However, to accommodate heterogeneity and publication bias, high-quality studies are required to further comparative effectiveness analyses to verify the efficacy of ultrasound detection.

Perineural invasion in cervical cancer: pay attention to the indications of nerve-sparing radical hysterectomy.

Perineural invasion (PNI) in early-stage cervical cancer, is associated with multiple high-risk factors and represents a poor outcome in the patients. For nerve-sparing radical hysterectomy (NSRH) to become a standard and widely used treatment for cervical cancer, we need to define its oncological safety, and to establish standardized surgical procedures and indications of NSRH. Here, we review the definition and mechanisms, and clinical significance of PNI in cervical cancer, and discuss the indications of NSRH. PNI should be regarded as one of the main pathological features of cervical cancer and a factor affecting prognosis. A deeper understanding of PNI in cervical cancer, hopefully, will provide clear indications of NSRH.

Sonographic image of cervix epithelioid trophoblastic tumor coexisting with mucinous adenocarcinoma in a postmenopausal woman: A case report.

RATIONALE: Epithelioid trophoblastic tumor (ETT) is a distinctive but rare gestational trophoblastic neoplasia (GTN) composed of chorionic-type intermediate trophoblast cells. Approximately 50% ETT arose from the uterine cervix or lower uterine segment following a previous pregnancy with vaginal bleeding. With its unusual ability to simulate an invasive epithelioid neoplasm, ETT frequently poses a diagnostic challenge, especially involving the uterine cervix. PATIENT CONCERNS: We herein report the case of a 60-year-old female with persistent vaginal bleeding and middle-level elevation of serum human chorionic gonadotropin (hCG). Ultrasound revealed a 3.0 × 2.7 cm well-circumscribed, strongly echogenic lesion in the cervix, with a peripheral pattern of Doppler signals. The enhanced pattern by contrast-enhanced ultrasound displayed strong peripheral enhancement accompanied with globular appearance, then centripetal filling completely, and fading away rapidly. DIAGNOSES: The final pathological diagnosis was ETT accompanying mucinous adenocarcinoma. INTERVENTIONS: Due to the pre-operative evaluation of a presumed IB2 cervix mucinous adenocarcinoma, the patient was treated with 2 courses of neoadjuvant chemotherapy followed by radical hysterectomy. OUTCOMES: The patient is currently disease-free for the past 1 year. LESSONS: This case report demonstrates that sonographic image of tumor shapes and blood flow could be helpful in differentiating ETT from another GTN and enable more accurate diagnosis before treatment.

Laparoscopic surgery on broken points for uterine sarcoma in the early stage decrease prognosis.

Uterine sarcoma, a rare solid tumor in uterus, is difficult to identify in the early stage from some benign uterine tumors, such as uterine fibroids. Hence, uterine sarcoma may be treated in the same way as uterine fibroids; and this may not be found until pathological diagnosis. Consequently, this can lead to tumor's abdominal spread, planting and local invasive growth, resulting in an early uterine sarcoma, an increased relapse rate after surgery and a decreased survival. Therefore, it's important to avoid these unintended and iatrogenic complications through an accurate diagnosis and an appropriate surgical approach. The surgical staging and a complete resection of the tumor are both important for patients' prognosis. In this review, we will discuss the laparoscopic surgery for uterine sarcoma in the early stage and patients' prognosis.

Papillary thyroid cancer located in malignant struma ovarii with omentum metastasis: a case report and review of the literature.

BACKGROUND: The present of malignant transformation in struma ovarii is exceedingly rare. Malignant struma ovarii is usually asymptomatic and infrequently diagnosed preoperatively. Because of its rarity, there is no consensus about diagnosis and management in the literature. CASE PRESENTATION: A 40-year-old female presented for her obstetric examination with an incidental finding of a pelvic mass. Patient was asymptomatic at presentation. A follow-up ultrasound confirmed the presence of a 3-cm mass in the left adnexa. Patient underwent a cytoreductive surgery (hysterectomy, bilateral salpingectomy and oophorectomy, omentectomy, appendectomy, and pelvic lymphadenectomy). Histopathology revealed a malignant struma ovarii with a focus of papillary thyroid carcinoma and the omentum metastasis. The patient with stage FIGO IIIc received 6 cycles of paclitaxel/carboplatin regimen after surgery. The patient subsequently had a thyroid scan that was normal with normal thyroid function. At a follow-up of 12 months, she is alive, in good clinical condition, and disease-free. CONCLUSIONS: Because of the rarity of these tumors and their lack of firm prognostic factors, treatment decisions should be made individually, based on pathologic and clinical parameters.

Perineural invasion as a prognostic factor for cervical cancer: a systematic review and meta-analysis.

BACKGROUND: Recent observational studies have reported that perineural invasion (PNI) may be a negative prognostic factor in cervical cancer. OBJECTIVES: The purpose of this meta-analysis is to systematically analyse the effect of PNI on overall survival and disease-free survival. SEARCH STRATEGY: The PubMed and Cochrane clinical trials databases were searched for articles with publication dates up to September 2013. SELECTION CRITERIA: Retrospective observational studies with survival analysis for perineural invasion after radical hysterectomy plus lymphadenectomy of cervical cancer were selected. DATA COLLECTION AND ANALYSIS: Trial characteristics and outcomes and quality measures based on the Newcastle-Ottawa scale (NOS) were independently extracted. The overall survival and disease-free survival of patients with PNI were measured using a hazard ratio (HR) for time to event outcomes. MAIN RESULTS: The meta-analysis of these studies demonstrated that cervical cancer with PNI was associated with a lower overall survival rate (HR 2.21, 95 % CI 1.36-3.59, P = 0.001). Although the disease-free survival was lower in the PNI group (HR 1.35, 95 % CI 0.78-2.31, P = 0.28), the results were not statistically significant. CONCLUSION: Patients with PNI-positive cervical cancer have a poor overall survival rate; therefore, we can conclude that perineural invasion (PNI) is an adverse prognostic factor in cervical cancer. Based on these results, PNI should be an independent prognostic factor for cervical cancer and the decision to proceed with adjuvant therapy after surgery.

TP53 K351N mutation-associated platinum resistance after neoadjuvant chemotherapy in patients with advanced ovarian cancer.

OBJECTIVE: TP53 K351N mutation is associated with acquired cisplatin resistance in ovarian cancer cells following exposure to cisplatin. We investigated the effect of TP53 K351N mutation on outcome in patients with epithelial ovarian cancer (EOC) who received platinum-based chemotherapy. METHODS: We assessed TP53 K351N mutations by allele specific real-time PCR (AS-PCR) and DNA sequencing in tumor samples of 153 patients with stage IIIC/IV EOC. Clinicopathologic and follow-up data were collected by a retrospective chart review. RESULTS: TP53 K351N mutations were detected in 8 (11.27%) of 71 patients who underwent neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) but not in 82 patients who underwent primary debulking surgery (PDS) (P<0.01). In patients with relapse within 6 months, the relapse rate was 14 (19.72%) of 71 patients for NACT-IDS compared to 15 (18.29%) of 82 patients for PDS (P=0.49), and TP53 K351N mutation was observed in 8 of NACT-IDS 14 patients (57.14% P<0.01). In the patients retreated at first recurrence within 6 months, 7 with TP53 K351N mutation of 14 NACT-IDS patients exhibited progression of disease, compared to 2 of PDS 15 patients (50.00% vs. 13.33%, P=0.04). The median disease-free survival (DFS) for NACT-IDS was 13.0 months compared to 15.0 months for PDS (P=0.02). In multivariate analysis, TP53 K351N mutation is an independent factor for shorter DFS in the patients who underwent NACT-IDS (HR=19.05; P=0.01). CONCLUSIONS: TP53 K351N mutation may be associated with induction of platinum resistance after NACT in advanced EOC.

Atractylenolide-I sensitizes human ovarian cancer cells to paclitaxel by blocking activation of TLR4/MyD88-dependent pathway.

Paclitaxel, a known TLR4 ligand, leads to activation of TLR4/MyD88-dependent pathway that mediates chemoresistance and tumor progression in epithelial ovarian carcinoma (EOC). Atractylenolide-I (AO-I), a novel TLR4-antagonizing agent, inhibits TLR4 signaling by interfering with the binding of LPS or paclitaxel to membrane TLR4 of human leukocytes. In this study, AO-I was found to attenuate paclitaxel-induced protein expression of IL-6, VEGF and survivin, and to enhance early apoptosis and growth inhibition in MyD88(+) EOC cells; AO-I was shown to fit into the hydrophobic pocket of human MD-2 and to partially overlap with the binding site of paclitaxel by docking simulations, suggesting that AO-I may block the MD-2-mediated TLR4/MyD88-dependent paclitaxel signaling in MyD88(+) EOC cells. Therefore, AO-I could significantly sensitize the response of MyD88(+) EOC cells to paclitaxel by blocking MD-2-mediated TLR4/MyD88 signaling, and that AO-I-paclitaxel combination could be a promising strategy for the treatment of EOC with a functional TLR4/MyD88/NF-κB pathway.

[Multicenter randomized controlled clinical study for the operative treatment of malignant ovarian germ cell tumors].

OBJECTIVE: To investigate the operative treatment for first-treated patients with malignant ovarian germ cell tumors who need preservation of fertility. METHODS: The clinical data of 105 patients who were treated with fertility-sparing surgery in 11 hospitals from 1992 to 2010 were collected to evaluate the outcomes of different primary surgical operative procedures. All 105 cases were performed the surgeries that preserved fertility and divided into three groups according to the surgical approaches, comprehensive staging surgery group: 47 cases (44.8%) received comprehensive staging surgeries that including the ipsilateral oophorectomy + omentectomy + retropertoneal lymph node dissection ± appendectomy + multiple biopsies;oophorectomy group:45 cases (42.9%)received ipsilateral oophorectomy ± biopsy of contralateral ovary ± omentectomy;tumor resection group:13 cases (12.4%) received enucleation of the mass with preservation of the ovary. Differences were compared among the three groups of patients in the surgery-related indicators, complications, fertility and prognosis. RESULTS: (1) Surgery-related indicators:the average blood loss of the comprehensive staging surgery group, the oophorectomy group and the tumor resection group were 496, 104 and 253 ml, the mean operation time were 176, 114 and 122 minutes, respectively, and there were significant differences among three groups (P = 0.011, P = 0.000). (2) Complication:the surgical complication rates of the three groups were 17% (8/47), 0 and 1/13, with significant differences (P = 0.015). (3) Reproductive function status: the pregnancy rate and birth rate of the three groups were no significant differences (9/19 vs. 7/19 vs. 2/3, P = 0.515; 8/19 vs. 5/19 vs. 2/3, P = 0.636). (4) PROGNOSIS: the recurrence rate of the three groups were significant differences [13% (6/47) vs. 0 vs. 2/13, P = 0.013], but the death rate with no significant differences [6% (3/47) vs. 0 vs. 0, P = 0.129]; The five-year survival rate of three different groups were 89%, 100% and 100% (P > 0.05), while disease free survival rate were 85%, 100% and 83% (P < 0.05), respectively. CONCLUSIONS: Compared with comprehensive staging surgery, oophorectomy group have higher surgical security and satisfactory prognosis, considerable pregnancy rates and birth rate. The tumor resection security may be reliable, but the prognosis is poor.

[Therapeutic evaluation of cisplatin, etoposide, and bleomycin chemotherapy regimen in high-risk gestational trophoblastic neoplasia].

OBJECTIVE: To evaluate the effectiveness and safety of combination chemotherapy with bleomycin, etoposide and cisplatin (BEP) regimen on the patients with high-risk gestational trophoblastic neoplasia (GTN). METHODS: Forty-two patients with high-risk GTN admitted in Sichuan Cancer Hospital between Jan.1997 and Oct. 2011 were analyzed retrospectively. The International Federation of Gynecology and Obstetrics (FIGO) prognostic score of all patients was more than 7. The mean age of patients was 30.2 years (range 20 - 49 years). All patients were treated with more than two cycles BEP regimen and followed up to the patients' death or at the end of Feb.2012. The clinical response, toxicity and the occurrence of secondary tumors were investigated. RESULTS: Forty-two high-risk GTN patients received the total of 251 courses of the BEP regimen, the average number of courses for each patient was 6.0 courses. Thirty-seven patients achieved complete remission and 5 patients showed drug-resistant. The total complete remission rate of BEP regimen was 88% (37/42). Among the complete remission patients, the total courses of BEP regimen of cases getting normal serum ß-hCG level was 129 courses (average 3.5 courses), and the total courses of cases achieving complete remission was 227 courses (average 6.1 courses). Among the 37 complete remission patients, 31 cases were treated with BEP regimen chemotherapy alone, 4 patients with BEP regimen chemotherapy combined with surgical treatment (1 case had no cancer after surgery) and 2 cases with BEP regimen chemotherapy combined with radiation therapy. Therefore, the complete remission rate of BEP regimen chemotherapy alone was 74% (31/42). There were 5 patients who showed drug-resistance after 24 courses of BEP regimen chemotherapy (average 4.8 courses), then received etoposide, methotrexate and dactinomycin (EMA)/cyclophosphamide and vincristine sulfate (CO) regimen chemotherapy after drug-resistance, 2 cases combined with radiation therapy, 1 case combined with surgical treatment. Ultimately, 4 cases achieved complete remission, 1 case died of cancer. The major toxicities of BEP regimen were included bone marrow suppression, digestive tract side effect and alopecic, followed by mild peripheral neuritis and abnormal liver function, rare cases of mild pulmonary toxicity. There were no severe anaphylaxis and obvious impairment of cardiac, liver, pulmonary and kidney function, except 1 patient (49 years old) had grade IV bone marrow suppression and pulmonary fibrosis worsened after chemotherapy. The bone marrow suppression was mainly I-III degree neutropenia, and Incidence rate was 66.5% (167/251). All the survival patients without secondary tumor. CONCLUSION: For young high-risk GTN patients, BEP regimen chemotherapy may be safe and effective.

Prognostic significance of MyD88 expression by human epithelial ovarian carcinoma cells.

BACKGROUND: MyD88 is an adaptor protein for TLR-4 signaling known to mediate paclitaxel resistance in epithelial ovarian carcinoma (EOC). This study examined the clinical significance of MyD88 expression in EOC. METHODS: MyD88 and TLR-4 expression were examined by immunocytochemistry in 109 specimens of ovarian tissues, comprising EOC (N = 83), borderline tumors (N = 9), benign cysts (N = 9) and normal ovarian tissue (N = 8), and clinical data collected by a retrospective chart review. The correlations between MyD88 expression and clinicopathological factors and outcomes were analyzed. RESULTS: TLR-4 expression was detected frequently in all the ovarian tissues. Distinct MyD88 expression was showed in EOC (64 of 83, 77.1 %), in borderline tumors (5 of 9, 55.6 %) and in benign cysts (3 of 9, 33.3 %), and normal ovarian tissue showed no MyD88 expression. Positive MyD88 expression significantly correlated with shorter disease-free and overall survival for EOC (P < 0.0001 and P = 0.0031), and high MyD88 expression was significantly correlated with tumor metastasis (P = 0.0012) for EOC. Univariate and multivariate analyses revealed that MyD88 expression was an independent prognostic factor for disease-free survival and overall survival for EOC. CONCLUSION: Our data indicate that MyD88 expression is a significantly poor prognostic factor for EOC. A better understanding of the role of MyD88 expression in disease progression and outcome may be helpful for development of novel chemotherapies for patients with EOC.

[Influence of human epithelial ovarian cancer HO-8910 cells with modified survivin gene on the cell cycle distribution and chemosensitivity].

OBJECTIVE: To study the influence of survivin mutant-T34A (survivin(T34A)) and survivin deletant-N-terminal 8 amino acids residues (survivin(N-8AA)) on the cell cycle distribution and chemosensitivity in human ovarian cancer HO-8910 cells for explorating the roles of modified survivin-mediated apoptosis induced by chemotherapeutic agents and possible signaling pathways involved. METHODS: pcDNA3.1 plasmid contained wild-type, survivin(T34A) and survivin(N-8AA) genes were transfected into HO-8910 cells, respectively, the control groups were HO-8910 cells transfected with pcDNA3.1 plasmids. The expression of mRNA was examined by reverse transcription(RT) PCR and identified by DNA sequencing; the cell cycles were determined by flow cytometer analysis (FCM); the growth inhibitions rate of cisplatin (DDP), paclitaxel (PTX) and LY294002 on the transfected cells were determined using methyl thiazolyl tetrazolium (MTT) assay. RESULTS: (1) The RT-PCR procedures and genome sequences showed that the survivin mRNA were expressed stable in the transfected HO-8910 cells. (2) There was lower percent of G(0)/G(1) phase cells in SN-HO-8910 cells than that in PC-HO-8910 cells (44.72% vs. 49.64%, P < 0.05); while higher percentage of G(2)/M phase and S phase cells (1.06% and 54.22% vs. 0.56% and 49.80%, P < 0.05). There was lower the G(2)/M phase and S phase cells in M-HO-8910 cells 0.16% and 36.33%, than that in PC-HO-8910 cells (P < 0.05); while higher percentage of G(0)/G(1) phase cells (63.51%, P < 0.05). G(0)/G(1), G(2)/M and S phase cells in Sur-HO-8910 cells were 54.46%, 0.62% and 44.92%, and there were not significantly difference (P > 0.05), compared to those in PC-HO-8910 cells. (3) The inhibitory concentration (IC(50)) of DDP and PTX were higher in Sur-HO-8910 cells than those in control cells [(20.4 ± 6.1) vs. (14.4 ± 3.9) µmol/L, (36.7 ± 4.0) vs. (28.6 ± 3.6) µmol/L; all P < 0.05]. The IC(50) of DDP and LY294002 in SN-HO-8910 cells were lower than those in control cells [(7.6 ± 1.0) vs. (14.4 ± 3.9) µmol/L, (13.2 ± 4.0) vs. (41.0 ± 7.9) µmol/L; all P < 0.01]. The IC(50) of PTX [(37.9 ± 4.8) µmol/L] in SN-HO-8910 cells were higher than that in control cells (P < 0.05). The IC(50) of DDP in M-HO-8910 cells [(9.9 ± 1.2) µmol/L] were lower than that in control cells (P < 0.05), and the IC(50) of LY294002 in M-HO-8910 cells [(66.9 ± 4.8) µmol/L] higher than that in control cells (P < 0.01). CONCLUSIONS: The changes of cells cycle distribution caused by survivin(T34A) or survivin(N-8AA) enhanced the G(2)/M cell cycle-dependent chemosensitivity of PTX. Compared to survivin(T34A), survivin(N-8AA) preferentially to mediate the cytotoxicity of DDP and LY294002, suggesting that it may be related to the cell cycle-dependence of survivin function and to blockage of the formation of its active dimer.

Distribution of human papillomavirus genotypes in archival cervical lesions in eastern inner Mongolian autonomous region, China.

INTRODUCTION: Human papillomavirus (HPV) is the main etiologic factor for cervical cancer (CC). To investigate the prevalence of HPV types in archival CC and its precursors collected form Tongliao area, which is located in the east of Inner Mongolian autonomous region, China, and compare the genotype distribution of HPV in cervical lesions between Han Chinese and Mongolian. METHODS: The infections of HPV in a total of 175 cases of formalin-fixed, paraffin-embedded samples, including 71 low-grade squamous intraepithelial lesions (LSIL), 27 high-grade squamous intraepithelial lesions (HSIL), and 77 CC were detected by the combination of consensus primers nested polymerase chain reaction (PCR) and type-specific primers nested PCR. RESULTS: Overall, HPV prevalence was 93.5% in CC, 92.6% in HSIL, and 63.4% in LSIL. Human papillomavirus 16 was the most predominant HPV type in all cervical lesions, detected in 83.1% of CC, 77.8% of HSIL, and 33.8% of LSIL. Human papillomavirus 45 was the second most predominant HPV type in CC (16.9%) and HSIL (11.1%). Human papillomavirus 33 was the second most predominant HPV type in LSIL (8.5%). Human papillomavirus 18, equal with HPV 45, was the second most common type in Mongolian CC (15.6%), whereas in Han Chinese specimens, no HPV 18 was found. CONCLUSIONS: The prevalence of HPV 45 in CC and HSIL in Tongliao area were relatively higher than other regions of China. Comparing the distribution of HPV types in Han Chinese and Mongolian, the prevalence of HPV 18 in CC from Mongolian was significantly higher than that in Han Chinese.

Profile of physical status and gene variation of human papillomavirus 58 genome in cervical cancer.

Epidemiological studies have shown that human papillomavirus 58 (HPV 58) is found at a relatively high frequency in east Asia and some regions of Central and South America. To investigate the physical status of HPV 58 and analyse sequence variations of HPV 58 in cervical cancer patients, the HPV 58 genome in 37 HPV 58-positive cervical cancer specimens collected from China were investigated by a mapping analysis based on nested PCR and nucleotide sequencing. A pure integrated genome was found in 78.4 % (29/37) of specimens, which is much higher than that found in previous studies. Multiple disruptions were first found among the integrated HPV 58 genomes in 51.7 % (15/29) of specimens. Among the 7824 bp of the HPV 58 genome, 119 (1.52 %) nucleotide positions were found to be variable, and 45 of them lead to amino acid changes. Phylogenetic analyses, based on partial L1 sequences of 14 variants isolated in previous studies and this study, show that two main groups were observed in HPV 58 variants, the prototype or prototype-like group and the non-prototype-like group.