Sectioning protocol determines accuracy of intraoperative pathological examination of sentinel lymph node in cervical cancer: A systematic review and meta-analysis.

OBJECTIVES: To determine the diagnostic performance and optimal protocol of frozen section examination (FSE) in SLNB for cervical cancer. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure were searched from inception to July 30, 2019, for studies concerning SLNB with FSE in cervical cancer. Sensitivity of FSE in detecting SLN metastasis was the primary diagnostic indicator for evaluation. RESULTS: The pooled sensitivity of FSE among 31 eligible studies (1887 patients) was 0.77 (95% CI 0.66-0.85) with high heterogeneity (I2 = 69.73%). Two representative sectioning protocols for FSE were identified from 26 studies, described as equatorial (E-protocol, SLN was bisected) and latitudinal (L-protocol, SLN was cut at intervals). Meta-regression showed that FSE protocol was the only source of heterogeneity (p < 0.001). The pooled sensitivity was 0.86 (95% CI 0.79-0.91, I2 = 0%) and 0.59 (0.46-0.72, I2 = 58.47%) for FSE using L- (13 studies, 650 patients) and E- (13 studies, 1047 patients) protocol, respectively. Among the available data, marcometastases (>2 mm) were missed in 4 and 20 patients; small-volume metastases (≤2 mm) were detected in 13 and 2 patients, respectively, under L- and E-protocol. The pooled sensitivity of FSE using L-protocol would reach 0.97 (95% CI 0.89-0.99) if only marcometastases were considered. These findings were robust to sensitivity analyses. CONCLUSION: The sectioning protocol determines the accuracy of FSE in SLNB. With L-protocol, FSE can provide precise intraoperative pathology for SLNB, which enables immediate decision-making for individualized managements.

MicroRNA-373 functions as an oncogene and targets YOD1 gene in cervical cancer.

miR-373 was reported to be elevated in several tumors; however, the role of miR-373 in cervical cancer has not been investigated. In this study we aimed to investigate the role of miR-373 in tumorigenicity of cervical cancer cells in vivo and in vitro. The expression of miR-373 was investigated using real-time reverse transcription-polymerase chain reaction assay in 45 cervical specimens and cervical cancer cell lines. The role of miR-373 in tumorigenicity of cervical cancer cells was assessed by cell proliferation, colony formation in vitro as well as tumor growth assays in vivo with the overexpression of miR-373 or gene silencing. The functional target gene of miR-373 in cervical cancer cells was identified using integrated bioinformatics analysis, gene expression arrays, and luciferase assay. We founded that the expression of miR-373 is upregulated in human cervical cancer tissues and cervical carcinoma cell lines when compared to the corresponding noncancerous tissues. Ectopic overexpression of miR-373 in human cervical cancer cells promoted cell growth in vitro and tumorigenicity in vivo, whereas silencing the expression of miR-373 decreased the rate of cell growth. YOD1 was identified as a direct and functional target of miR-373 in cervical cancer cells. Expression levels of miR-373 were inversely correlated with YOD1 levels in human cervical cancer tissues. RNAi-mediated knockdown of YOD1 phenocopied the proliferation-promoting effect of miR-373. Moreover, overexpression of YOD1 abrogated miR-373-induced proliferation of cervical cancer cells. These results demonstrate that miR-373 increases proliferation by directly targeting YOD1, a new potential therapeutic target in cervical cancer.

[Application of carbon nanoparticles in the laparoscopic sentinel lymph node detection in patients with cervical cancer].

OBJECTIVE: To explore the role of laparoscopic sentinel lymph node(SLN) detection with carbon nanoparticles tracer in cervical carcinoma. METHODS: Totally 21 patients with confirmed early cervical cancer were enrolled in this study.Before laparoscopic extended hysterectomy and pelvic lymphadenoetomy(and para-aortic lymphadenoectomy) , they were injected with carbon nanoparticles suspension injection tracer from cervical neck before surgery. The black-staining lymph nodes were cut as SLN under the laparoscope for routine pathological examination. RESULTS: Of these 21 patients, at least one SLN was successfully detected in 20 patients(95.24%) , and a total of 158 SLNs were detected.The conventional pathology results suggested that 5 patients(23.81%) had positive lymph nodes(n=16, including 14 in 4 patients) . The new approach showed a sensitivity of 80.0%(4/5) , accuracy of 100.0%(20/20) , and negative predictive value of 100.0%(16/16) for SLN detection. CONCLUSION: Laparoscopic SLN detection with carbon nanoparticles tracer is a relative safe and sensitive method for in cervical carcinoma.

[Short term clinical outcomes of laparoscopic fertility preserving radical hysterectomy in the management of early stage cervical cancer].

OBJECTIVE: To investigate the feasibility and effectiveness of laparoscopic radical trachelectomy and lymphadenectomy in the treatment of early-stage cervical cancer. METHODS: The clinical data of 6 patients (stage 1a2 to 1b1), who underwent laparoscopic fertility-preserving radical operation for cervical cancer in our department from February 2009 to October 2010, were retrospectively analyzed in terms of operation duration, intra-operative blood loss, postoperative pathology, complications, and pregnancy. RESULTS: Both radical resection of cervical and pelvic lymph node dissection were completed under laparoscopy, and only the cervical and vaginal cuffs were closed from vagina. The operation duration ranged 155-210 min (mean: 185 min) and the intra-operative blood loss was approximately 60-120 ml(mean: 105 ml). The average length of hospital stay was 18 days without complications, postoperative infection, and bleeding. Postoperative pathology showed no lymph node metastasis, and no ligament, blood vessels, vaginal cutting margin, or upper part of cervix was invaded by tumor cells. During the 8-20-month follow-up, 1 patient had become pregnant for 4 months and no case experienced tumor recurrence. CONCLUSION: Laparoscopic fertility-preserving lymphadenectomy and radical trachelectomy is feasible for patients with early-stage cervical cancer who have strong wish to have a child.

[Effectiveness and safety of laparoscopic presacral neurectomy in treating endometriosis-associated pain].

OBJECTIVE: To explore the effectiveness and safety of laparoscopic presacral neurectomy (LPN) in treating endometriosis-associated pain. METHODS: Totally 64 patients with endometriosis were divided into two groups using prospective non-random method. Patients in the control group received only the conventional laparoscopic resection of endometriosis lesions, while patients in the LPN group underwent LPN in addition to the resection of endometriosis lesions. The pre-operative pain scores, intra-operative staging results, surgical duration, intra-surgical blood loss, post-operative pain relief were compared between these two groups. RESULTS: These two groups showed no significant differences in terms of age, body weight, pre-operative pain score, surgery staging, surgical duration, and intra-operative blood loss (all P > 0.05). All patients were followed up for 6 to 18 months (median: 12.8 months). The post-operative pain relief rate was 89.28% (25/ 28) in LPN group and 61.29% (19/31) in the control group (P = 0.030). CONCLUSION: LPN can effectively and safely in treating endometriosis and its associated pain.

Carnosic acid cooperates with tamoxifen to induce apoptosis associated with Caspase-3 activation in breast cancer cells in vitro and in vivo.

Tamoxifen is known as a standard therapeutic treatment for estrogen receptor-positive breast cancer, which down-regulates breast cancer mortality by 31% approximately. Carnosic acid is a phenolic diterpene, which has anti-cancer, anti-inflammation, anti-diabetic and anti-bacterial properties, generated by various species coming from Lamiaceae family. The breast cancer is reported as one of the most common tumors among women worldwide. In our study, the possible benefits of carnosic acid cooperation with tamoxifen for breast cancer treatment in vitro and in vivo were investigated. Carnosic acid and tamoxifen cooperation led to apoptosis in breast cancer cells. Caspase-3 signaling pathway was promoted for carnosic acid and tamoxifen co-treatment. Consistently, anti-apoptotic molecules Bcl-2 and Bcl-xl were down-regulated, while pro-apoptotic signals Bax and Bad were up-regulated. The elevation of decoy receptor 1 and 2 (DcR1 and DcR2) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were enhanced for carnosic acid and tamoxifen cooperation. Furthermore, the mouse xenograft model in vivo suggested that carnosic acid and tamoxifen combined therapy inhibited breast cancer growth in comparison to the carnosic acid or tamoxifen monotherapy. Our study supplies a novel therapeutic strategy to induce apoptosis for suppressing breast cancer, which was relied on Caspase-3/TRAIL activation.

Phenethyl isothiocyanate suppresses the metastasis of ovarian cancer associated with the inhibition of CRM1-mediated nuclear export and mTOR-STAT3 pathway.

Epithelial ovarian cancer is prone to metastasizing at an early stage, but their mechanisms remain unclear. CRM1 is an important nuclear exportin and inhibitors targeting CRM1 has been explored as an anti-cancer strategy. In previous study, we observed that PEITC could combine with the hydrophobic pocket of CRM1. In this study, we focused on the effects of PEITC on EOC and its mechanisms. Results showed that IC50 values of PEITC on SKOV3 and HO8910 cell line were 42.14 µM and 37.29 µM, respectively. PEITC inhibits the migration and invasion of SKOV3 and HO8910 cells in vitro. Oral administration of 10 µmol PEITC suppressed the metastasis of EOC in a xenograft mouse model in vivo. PEITC treatment decreased the expressions of CRM1 and mTOR (cargo protein of CRM1) in EOC cell lines and in xenograft mouse tissues. Moreover, CRM1-mediated nuclear export was attenuated by PEITC, mTOR accumulated in nucleus, expressions of mTORS2448 and downstream effectors STAT3S727, MMP2 and MMP9 were decreased in a dose- and time-dependent manner. Furthermore, immunohistochemical analysis showed that CRM1 and mTOR were increased in EOC tissues compared with benign ovarian tumors, and related with advanced stage, type II EOC, positive peritoneal cytology and decreased overall survival. In addition, CRM1 was positively correlated with mTOR levels. In conclusion, our data demonstrated that PEITC suppresses the metastasis of EOC through inhibiting CRM1-mediated nuclear export, subsequently suppressing the mTOR-STAT3 pathway. Both CRM1 and mTOR were increased in EOC patients, providing a rationale for further clinical investigation of PEITC in EOC treatment.

[Mutations of human papillomavirus (HPV) 16 type L1 genes from cervical carcinoma biopsies in southern Xinjiang Uygur women].

OBJECTIVE: To study the mutations of Human Papillomavirus (HPV) 16 type L1 genes of cervical carcinoma biopsies from Uygur women in Southern Xinjiang, and analyze changes of L1 protein function. METHODS: The tissue DNA was extracted from cervical carcinoma biopsies. HPV16 L1 genes were amplified by PCR from the DNA HPV16 type L1 genes were sequenced and analyzed. RESULTS: The result of PCR showed that the positive rate of HPV16 L1 was 84.21% (16/19). These DNA were sequenced, and we found some mutations in comparison with the previously published sequence of prototype HPV16 L1. Some of the mutations changed the triplet codes, subsequently led to changes of amino acids. The mutations of all thirteen HPV16 L1 fragments formed six patterns (XJL1-1 approximately XJL1-6) at nucleic acid level. Compare to HPV16 prototype, their homology were 99.69% to 99.87%. There were four mutations in nucleic acid sequences of XJL1-1, which occurred also in XJL1-2 approximately XJL1-6. Moreover, there are other mutations in XJL1-2 approximately XJL1-6 besides the four mutations in XJ L1-1. The mutations of all thirteen HPV16 L1 fragments formed four patterns at amino acid level, among the mutations XJL1-1/2/3 was by 76.92% (8/13). CONCLUSION: HPV16 type L1 genes from cervical carcinoma biopsies occurred some mutations in Uygur women from southern Xinjiang, and formed several patterns as well as mainstream pattern. The mutations of L1 proteins changed its hydrophobicity and antigenicity. The research suggested that the mutations of HPV16 type L1 genes associated with HPV16 phylogenesis and escape from immune recognition.

[Investigation on the gene expression pattern in cervical squamous cell carcinoma of uygur].

OBJECTIVE: To investigate the differentially expressed gene in cervical squamous cell carcinoma of uygur and normal cervical tissue using gene chip. METHOD: Gene chips containing 2,048 human genes were used to investigate the gene expression pattern of 3 samples of cervical cancer. RESULT: By applying this gene chip we identified 64 differentially expressed genes in all 3 clinical cervical cancer samples, and we further identified 53 upregulated and 11 downregulated genes for functional analysis. CONCLUSION: The analysis of gene expression pattern of tumor based on gene chip can realize high-throughput screening of the genes associated with the cervical cancer.

[Analysis of human papillomavirus 16 E6 oncogene mutation in Xinjiang Uygur women with cervical carcinoma].

BACKGROUND & OBJECTIVE: High-risk human papillomaviruses(HPVs),such as HPV16, and HPV18,are major causes of cervical cancer (CC), and HPV16 was found most frequently in CC patients. HPV16E6 is one of major oncogenes. In some region, specific E6 mutation is considered as dangerous factor causing CC. There is a very high incidence of CC in southern Xinjiang, where the Uygur are the majority. As we reported before, we found HPV16E6 mutation from this district. This study was designed to investigate distribution of the mutation in CC of Xinjiang Uygur women, and the relationship between the mutation and high incidence of CC in southern Xinjiang. METHODS: The tissue DNA was extracted from 35 CC biopsies of Xinjiang Uygur Women. HPV16E6 gene was amplified by polymerase chain reaction (PCR) from the CC tissue DNA. The PCR fragments were sequenced and analyzed. RESULTS: The result of PCR showed that the positive rate of HPV16E6 was 82.86%(29/35); 26 of these 29 PCR fragments were sequenced and analyzed, 15 of them maintained prototype (57.69%), 11 have L83V mutation (34.62%), and 2 have L83V/D63E mutation (7.69%). CONCLUSIONS: There is mutation within the HPV16E6 gene in CC of Xinjiang Uygur women. Our research suggested that the distribution of HPV16 prototype and HPV16E6 mutation might be associated with high incidence of CC in southern Xinjiang.