Inhibition of Hec1 expression enhances the sensitivity of human ovarian cancer cells to paclitaxel.

AIM: Hec1, a member of the Ndc80 kinetochore complex, is highly expressed in cancers. The aim of this study was to explore the role and mechanism of action of Hec1 with respect to the cytotoxicity of paclitaxel in ovarian cancer. METHODS: Thirty ovarian cancer samples and 6 normal ovarian samples were collected. Hec1 expression in these samples was determined with immunohistochemistry. Ovarian cancer cell lines A2780, OV2008, C13K, SKOV3, and CAOV3 and A2780/Taxol were examined. Cell apoptosis and cell cycle analysis were detected with flow cytometric technique. siRNA was used to delete Hec1 in the cells. The expression of related mRNAs and proteins was measured using RT-PCR and Western blot analysis, respectively. RESULTS: Hec1 expression was significantly higher in ovarian cancer samples than in normal ovarian samples, and was associated with paclitaxel-resistance and poor prognosis. Among the 6 ovarian cancer cell lines examined, Hec1 expression was highest in paclitaxel-resistant A2780/Taxol cells, and lowest in A2780 cells. Depleting Hec1 in A2780/Taxol cells with siRNA decreased the IC50 value of paclitaxel by more than 10-fold (from 590±26.7 to 45.6±19.4 nmol/L). Depleting Hec1 in A2780 cells had no significant effect on the paclitaxel sensitivity. In paclitaxel-treated A2780/Taxol cells, depleting Hec1 significantly increased the cleaved PARP and Bax protein levels, and decreased the Bcl-xL protein level. CONCLUSION: Hec1 overexpression is associated with the progression and poor prognosis of ovarian cancer. Inhibition of Hec1 expression can sensitize ovarian cancer cells to paclitaxel.

Adjuvant Chemotherapy May Not Be Necessary for Women with Stage IC1 Epithelial Ovarian Cancer.

OBJECTIVE: To determine whether adjuvant chemotherapy improves the prognoses in women with stage IC1 epithelial ovarian cancer (EOC). METHODS: All eligible women diagnosed with stage IC1 EOC from 2003 to 2019 in Tongji Hospital were included. Patient characteristics, tumor features, surgical types, and chemotherapeutic treatments were collected. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate progression-free survival (PFS) and overall survival (OS). RESULTS: Of the 140 patients (median age: 47 years old), 13 patients did not receive chemotherapy, and 127 received adjuvant chemotherapy. Kaplan-Meier analysis indicated that adjuvant chemotherapy offered no obvious improvements in PFS or OS. Subgroup analysis was conducted to adjust for the significant difference in incomplete staging surgery between the two groups, and chemotherapy still showed no benefit for survival. Cox regression analysis indicated that incomplete staging surgery was a risk factor for a worse PFS and that adjuvant chemotherapy remained unrelated to the prognosis. The patients were further divided based on the National Comprehensive Cancer Network recommendations: patients for whom observation is optional and chemotherapy would not improve the prognosis; and patients for whom chemotherapy is recommended. The results showed that postoperative chemotherapy had little correlation with survival. CONCLUSION: Our study suggests that postoperative chemotherapy may be unnecessary for patients with stage IC1 EOC. According to our results, incomplete staging surgery is a significant risk factor for PFS.

Integration of MRI-Based Radiomics Features, Clinicopathological Characteristics, and Blood Parameters: A Nomogram Model for Predicting Clinical Outcome in Nasopharyngeal Carcinoma.

Purpose: This study aimed to develop a nomogram model based on multiparametric magnetic resonance imaging (MRI) radiomics features, clinicopathological characteristics, and blood parameters to predict the progression-free survival (PFS) of patients with nasopharyngeal carcinoma (NPC). Methods: A total of 462 patients with pathologically confirmed nonkeratinizing NPC treated at Sichuan Cancer Hospital were recruited from 2015 to 2019 and divided into training and validation cohorts at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) algorithm was used for radiomics feature dimension reduction and screening in the training cohort. Rad-score, age, sex, smoking and drinking habits, Ki-67, monocytes, monocyte ratio, and mean corpuscular volume were incorporated into a multivariate Cox proportional risk regression model to build a multifactorial nomogram. The concordance index (C-index) and decision curve analysis (DCA) were applied to estimate its efficacy. Results: Nine significant features associated with PFS were selected by LASSO and used to calculate the rad-score of each patient. The rad-score was verified as an independent prognostic factor for PFS in NPC. The survival analysis showed that those with lower rad-scores had longer PFS in both cohorts (p < 0.05). Compared with the tumor-node-metastasis staging system, the multifactorial nomogram had higher C-indexes (training cohorts: 0.819 vs. 0.610; validation cohorts: 0.820 vs. 0.602). Moreover, the DCA curve showed that this model could better predict progression within 50% threshold probability. Conclusion: A nomogram that combined MRI-based radiomics with clinicopathological characteristics and blood parameters improved the ability to predict progression in patients with NPC.

Outcomes of patients with pelvic leiomyosarcoma treated by surgery and relevant auxiliary diagnosis.

BACKGROUND: Leiomyosarcoma is a subtype of soft tissue sarcoma with adverse outcomes. Leiomyosarcoma accounts for nearly 70% of all uterine sarcomas and is responsible for a considerable proportion of deaths because of uterine cancer. Clinical characteristics and relevant diagnosis of pelvic leiomyosarcoma should be further explored. AIM: To identify the outcome and relevant perioperative evaluation of patients with pelvic leiomyosarcoma. METHODS: The Kaplan-Meier method was used to determine progression-free survival and overall survival rates. Factors predictive of outcomes were identified using univariate and multivariate Cox proportional hazards models. RESULTS: Fifty-one patients with pelvic leiomyosarcoma were enrolled and divided into two groups including uterine leiomyosarcoma and non-uterine leiomyosarcoma. Overall, 28.6% and 45.5% of uterine leiomyosarcoma and non-uterine leiomyosarcoma patients, respectively, had elevated carbohydrate antigen 125 levels, whereas 45.7% and 68.8%, respectively, underwent ultrasonography. Although 68.8% of uterine leiomyosarcoma patients were initially diagnosed with hysteromyoma, 72.7% of non-uterine leiomyosarcoma patients had pelvic and abdominal masses. Moreover, 93.3% of the recurrent lesions were detected using ultrasonography. Patients with International Federation of Gynaecology and Obstetrics (FIGO) stages III-IV disease had poorer progression-free survival values than those with FIGO stages I-II (P = 0.027) disease. FIGO stage was significantly associated with poor progression-free survival in the univariate (hazard ratio = 2.64, P = 0.03) and multivariate (hazard ratio = 2.49, P = 0.048) analyses. CONCLUSION: Serum tumour biomarkers cannot be used for pelvic leiomyosarcoma diagnosis. FIGO stage is critical to predict the outcome of uterine leiomyosarcoma. Ultrasonography is more reliable for postoperative follow-up than preoperative diagnosis.

Clinical characteristics and survival of patients with normal-sized ovarian carcinoma syndrome: Retrospective analysis of a single institution 10-year experiment.

BACKGROUND: Normal size ovarian cancer syndrome (NOCS) is a challenge for clinicians regarding timely diagnosis and management due to atypical clinical and imaging features. It is extremely rare with only a few cases reported in the literature. More data are needed to clarify its biological behavior and compare the differences with abnormal size ovarian cancer. AIM: To assess the clinical and pathological features of NOCS patients treated in our institution in the last 10 years and to explore risk factors for relapse and survival. METHODS: Patients who were pathologically diagnosed with NOCS between 2008 and 2018 were included. Papillary serous ovarian carcinoma (PSOC) patients were initially randomly recruited as the control group. Demographics, tumor characteristics, treatment procedures, and clinical follow-up were retrospectively collected. Risk factors for progression-free survival and overall survival were assessed. RESULTS: A total of 110 NOCS patients were included; 80 (72.7%) had primary adnexal carcinoma, two (1.8%) had mesotheliomas, 18 (16.4%) had extraovarian peritoneal serous papillary carcinoma, and eight (7.3%) had metastatic tumors. Carbohydrate antigen (CA)125 and ascites quantity were lower in the NOCS cohort than in the PSOC group. The only statistically significant risk factors for worse overall survival (P < 0.05) were the levels of CA199 and having fewer than six chemotherapy cycles. The 1-year, 3-year, and 5-year survival rates were 75.5%, 27.7%, and 13.8%, respectively. CONCLUSION: The clinical symptoms of the NOCS group are atypical, and the misdiagnosis rate is high. Ascites cytology and laparoscopic exploration are valuable in the early diagnosis to avoid a misdiagnosis. The level of CA199 is the most important predictor of overall survival, and more than six cycles of chemotherapy contributes to the increased survival rates of NOCS patients.

Influence of Different Quality Sperm on Early Embryo Morphokinetic Parameters and Cleavage Patterns: A Retrospective Time-lapse Study.

To investigate whether sperm with low concentration and motility can impact preimplantation embryos and to analyze how the effects present under a time-lapse incubation system, 2905 oocytes were collected from 219 couples between January 2014 and December 2015. Patients were divided into three groups according to sperm quality. Morphokinetic parameters and six cleavage patterns in the initial three cleavages were evaluated using the Primo Vision system. Embryo quality and clinic outcomes such as implantation rate, pregnancy rate and live birth rate were measured. The results showed that the concentration and motility of sperm correlated strongly with the rate of 2PN embryos, good-quality embryos on D3, blastocysts on D5/6 and good-quality embryos on D5/6. The time-lapse system recordings showed that compromised sperm quality could result in a significant delay in cc1 and a decrease in cc2, and impact embryo developmental potential mainly through large fragments or/and blastomere fragmentation in the initial three cleavages. In conclusion, sperm with low concentration and motility can have paternal effects on preimplantation embryos. These paternal effects present both as changes in morphokinetic parameters and cleavage patterns, which occur as early as fertilization and may cause severe damage to the preimplantation embryos.

Oncological and Reproductive Outcomes of Fertility-sparing Surgery in Women with Early-stage Epithelial Ovarian Carcinoma: A Multicenter Retrospective Study.

With delayed childbearing in women, preservation of fertility is an important issue for reproductive-age patients with epithelial ovarian carcinoma (EOC). Fertility-sparing surgery (FSS) can be considered in patients with early-stage disease in order to preserve fertility and improve quality of life. In order to evaluate oncological safety, attitudes toward childbearing and reproductive outcomes in women with EOC who underwent FSS, this multicenter retrospective study was conducted. Between January 2005 and December 2014, total of 87 young women with FIGO stage I EOC were included, with their clinicopathologic parameters in relation to disease-free survival (DFS) and overall survival (OS) assessed. Attitudes toward childbearing, ovarian function and fertility were studied in women undergoing FSS (n=36). As a result, in contrast to radical surgery, FSS did not affect prognosis by Kaplan-Meier curves (log-rank test; DFS: P=0.484; OS: P=0.125). However, two of the three recurrence cases and both death cases were in FSS group stage IC. All women undergoing FSS resumed regular menstrual periods after chemotherapy. Only 16 (44.44%) had tried to conceive, and 17 pregnancies occurred in 15 (93.75%) women. Among 20 women who did not attempt conception, the most common reason was not being married (70%), followed by already having children (15%). In summary, FSS is considered safe in young women with stage IA EOC. Regular menstruation and good obstetric outcomes can be achieved. This study also provides some insight into the attitudes and social factors regarding fertility in EOC patients.

CLDN1 expression in cervical cancer cells is related to tumor invasion and metastasis.

Even though infection with human papillomaviruses (HPV) is very important, it is not the sole cause of cervical cancer. Because it is known that genetic variations that result from HPV infection are probably the most important causes of cervical cancer, we used human whole genome array comparative genomic hybridization to detect the copy number variations of genes in cervical squamous cell carcinoma. The results of the array were validated by PCR, FISH and immunohistochemistry. We find that the copy number and protein expression of claudin-1 (CLDN1) increase with the progression of cervical cancer. The strong positive staining of CLDN1 in the cervical lymph node metastasis group received a significantly higher score than the staining in the group with no lymph node metastasis of cervical cancer tissues. The overexpression of CLDN1 in SiHa cells can increase anti-apoptosis ability and promote invasive ability of these cells accompanied by a decrease in expression of the epithelial marker E-cadherin as well as an increase in the expression of the mesenchymal marker vimentin. CLDN1 induces the epithelial-mesenchymal transition (EMT) through its interaction with SNAI1. Furthermore, we demonstrate that CLDN1 overexpression has significant effects on the growth and metastasis of xenografted tumors in athymic mice. These data suggest that CLDN1 promotes invasion and metastasis in cervical cancer cells via the expression of EMT/invasion-related genes. Therefore, CLDN1 could be a potential therapeutic target for the treatment of cervical cancer.

[Expression of human telomerase reverse transcriptase in cervix cancer and its significance].

OBJECTIVE: To investigate the expression of human telomerase reverse transcriptase (hTERT) mRNA and protein in cervix cancer, cervical intraepithelial neoplasia (CIN) and normal cervix. METHODS: Expression of hTERT mRNA and the other two subunits of telomerase, human telomerase RNA component (hTR), human telomerase-associated protein (hTP1) was determined by RT-PCR in 3 cervix cancer cell lines, 2 diploid cell lines, 38 cases of cervix cancer, 16 cases of CIN and 20 cases of normal cervix. Telomerase activity was also examined by telomeric repeat amplification protocol enzyme-linked immunosorbent assay (TRAP-ELISA). Expression of hTERT protein was detected in all the cell lines and 101 cases of paraffinized cervix tissue sections. RESULTS: hTERT mRNA expression was detected in all of the three cervix cancer cell lines, 81.6% of cervix cancer, 37.5% of CIN, 5.0% of normal cervix, while in neither of the two diploid cell lines. The other two subunits of telomerase were prevalently expressed in all of the cell lines and most cervix tissues. There was a strong correlation between hTERT mRNA expression and telomerase activity. Immunostaining also revealed that hTERT protein was expressed in all three cervix cancer cell lines, 65.5% of cervix cancer, 28.0% of CIN and 4.8% of normal cervix. CONCLUSION: Up-regulation of hTERT may play an important role in the development of CIN and cervix cancer, hTERT could be used as an early diagnostic biomarker for cervix cancer.

[Effects of conditionally replicating adenovirus Adv5/dE1A-Aschk1 on isolated human umbilical endothelial cells].

BACKGROUND & OBJECTIVE: Replicating adenovirus, with the favorable features of efficient transduction and multiple in malignant cells, represent a promising option for gene therapy. Its influence on vascular endothelia in vivo is an important indicator for safety evaluation. This study was to explore the effects of conditionally replicating adenovirus Adv5/dE1A-Aschk1 on proliferating and resting endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were isolated by filling umbilical veins with digestive enzyme solution. HUVECs were cultured and observed with immunofluorescent staining and under electron microscope to identify endothelial cells. The oncolytic effects of Adv5/dE1A-Aschk1 on HeLa and endothelial cells were measured by cytopathic effect assay (CPE)û its effect on the proliferation of endothelial cells was measured by MTT assay. Cell apoptosis after treatment of Adv5/dE1A-Aschk1 alone or in combination with irradiation was measured by flow cytometry (FCM). RESULTS: Highly purified endothelial cells were isolated. Adv5/dE1A-Aschk1 lysed HeLa cells in a replication-dependent fashion, but did not exhibit detectable cytopathic effects on resting endothelial cells at a multiplicity of infection (MOI) of 500. The inhibitory effect of Adv5/dE1A-Aschk1 on the proliferation of endothelial cells increased with the increase of viral titer. When treated with Adv5/dE1A-Aschk1 at a MOI of 100 for 96 h, the proliferation inhibition rate of proliferating HUVECs was (22.0+/-2.5)%, but that of resting HUVECs was (13.0+/-2.3)%. When treated with Adv5/dE1A-Aschk1 combined irradiation, the apoptosis rate of resting HUVECs was (23.1+/-2.5)%, and that of proliferating HUVECs was (35.7+/-3.0)%. CONCLUSIONS: HUVECs may be taken as a good target for the research of conditionally replicating adenovirus. The viral titer for injuring endothelial cells is much higher than that for killing tumor cells, so Adv5/dE1A-Aschk1 has a wide range of therapeutic dosage. As compared with resting HUVECs, proliferating HUVECs are more likely to be lysed by Adv5/dE1A-Aschk1.