Efficacy of treatment patterns based on concurrent chemoradiotherapy in patients with stage IIB cervical squamous cell carcinoma.

PURPOSE: To assess survival of treatment patterns based on concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: Patients with stage IIB CSCC receiving CCRT were investigated from June 2012 to June 2019 in Guangxi Medical University Cancer Hospital. Baseline characteristics and treatment patterns were described. Survival between treatment patterns were compared using Kaplan-Meier methods. RESULTS: A total of 232 patients were included: 39.7% of patients received CCRT alone, 6.5% of patients received neoadjuvant chemotherapy (NACT) + CCRT, 45.6% of patients received CCRT + adjuvant chemotherapy (AC), and 8.2% of patients received NACT + CCRT + AC. CCRT + AC showed similar overall survival (OS; hazard ratio [HR] = 0.95, 95% confidence interval [CI]: 0.41-2.17; P = 0.894) and locoregional-free survival (LRFS; HR = 2.39, 95% CI: 0.45-12.63; P = 0.303) compared with CCRT. However, CCRT + AC had a worse distant metastasis-free survival (DMFS; HR = 5.39, 95% CI: 1.14-25.57; P = 0.034). After propensity score matching, CCRT + AC had comparable OS (HR = 0.89, 95% CI: 0.29-2.70; P = 0.833), LRFS (HR = 3.26, 95% CI: 0.30-35.38; P = 0.331), and DMFS (HR = 4.80, 95% CI: 0.55-42.26; P = 0.157) compared to CCRT. CONCLUSION: AC did not improve survival in patients with stage IIB CSCC receiving CCRT.

Neoadjuvant chemotherapy followed by surgery versus concurrent chemoradiotherapy in patients with stage IIB cervical squamous cell carcinoma: a retrospective cohort study.

PURPOSE: This study aims to compare treatment outcomes between neoadjuvant chemotherapy (NACT) followed by surgery and concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: We conducted a retrospective cohort study involving patients with stage IIB CSCC treated at Guangxi Medical University Cancer Hospital between June 2012 and June 2019. We compared overall survival (OS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) between the NACT + surgery and CCRT groups. RESULTS: A total of 257 patients were enrolled: 165 underwent NACT + surgery and 92 received CCRT. Before propensity score matching, the NACT + surgery group exhibited lower 5-year OS (68.2% vs. 85.6%; hazard ratio [HR] = 2.50, 95% confidence interval [CI]: 1.26-4.96; P = 0.009), LRFS (85.2% vs. 96.9%; HR = 5.88, 95% CI: 1.33-25.94; P = 0.019), and DMFS (81.9% vs. 97.4%; HR = 6.65, 95% CI: 1.51-29.23; P = 0.012) compared to the CCRT group. After propensity score matching, OS, LRFS, and DMFS remained worse in the NACT + surgery group compared to the CCRT group. CONCLUSION: NACT followed by surgery is associated with decreased OS, LRFS, and DMFS compared to CCRT among patients with stage IIB CSCC.

[Clinicopathologic analysis of small cell neuroendocrine carcinoma of the cervix].

OBJECTIVE: To analyse the clinico-pathologic characteristics, diagnosis, therapy and prognostic of small cell neuroendocrine carcinoma of the cervix (SCNCC). METHODS: The clinic-pathological features of 12 patients with SCNCC treated in Tumor Hospital of Guangxi Medical University, admitted during March 2006 to July 2010, were analyzed retrospectively. RESULTS: Of 12 patients, the mean age was 38.7 years (rang 28 - 57 years), 6 had stages Ib1-IIa, 6 had stages IIb-IV. Among 8 patients (Ib1-IIIb) underwent surgery, 4 of them received neoadjuvant chemotherapy, 8 of them received adjuvant chemotherapy and(or) radiotherapy. All had greater than one-half stromal invasion, 4 patients had positive pelvic lymph nodes metastases. The positive ratio of the chromogranin (CgA), synaptophysin, neuronspecific enolase (NSE), cytokeratins (CK), CD(56) tested by immunohistochemical staining were 8/12, 9/10, 4/4, 4/4, 4/4, respectively. Median follow-up period was 3 months (1 - 22 months). Among 8 patients underwent surgery, 2 patients developed lung metastases, 1 patient developed liver and lung metastases, 1 patient developed liver metastases concurrently with bone metastases, disease-free survival (DFS) were 3 months (Ib2 with positive lymph nodes), 4.6 months (IIa), 7 months (Ib1), 17 months (Ib2); 2 patient died (8.5 and 11.3 months, respectively) after surgery; 4 patients are alive and show no evidence of disease. Among 4 patients untreated, 1 patients received concurrent chemoradiation and are alive for 10.1 months. Two patient untreated (IIIb, IV) died after 0.6 and 1.3 months final diagnosis, respectively. One patient was lost follow-up. CONCLUSIONS: SCNCC is a highly malignant tumor with rare morbility, propensity for distant spread and dismal prognosis. Final diagnosis of SCNCC depends on pathomorphology and immunohistochemical analysis. Combined therapeutic modalities may in favor of survival in some patients.

[Impact on survival and quality of life of laparoscopic radical hysterectomy and pelvic lymphadenectomy to patients with early-stage cervical cancer].

OBJECTIVE: To compare intraoperative, pathologic, postoperative outcomes and quality of life of laparoscopic radical hysterectomy and pelvic lymphadenectomy (LRH + LPL) with abdominal radical hysterectomy and pelvic lymphadenectomy (ARH + APL) for patients with early-stage cervical cancer. METHODS: The consecutive cases with International Federation of Gynecology and Obstetrics (FIGO) stages Ia2-IIa cervical cancer who underwent surgery from Jan. 1, 2002 to Jan. 1, 2011 were documented, including 85 patients underwent LRH + LPL, and 85 patients underwent ARH + APL as control group. The clinical data of intraoperative, pathologic, postoperative outcomes and quality of life were compared between two groups. Survival data were estimated using Kaplan-Meier survival curves and compared with the log-rank test. Cox proportional hazards model was used for multivariate analysis. RESULTS: All but 2 surgical procedures were completed laparoscopically because of right common iliac vein vessel injuries. Mean operative time, it was longer for LRH + LPL than that for ARH + APL [(242 ± 74) minutes vs. (190 ± 61) minutes, P = 0.000]. Mean recovery time of intestines function was less for LRH + LPL than that for ARH + APL [(45 ± 7) hours vs. (63 ± 11) hours, P = 0.000]. Mean estimated blood loss was less for LRH + LPL than that for ARH + APL [(367 ± 252) ml vs. (460 ± 220) ml, P = 0.006]. Mean recovery time of urinary function was less that for LRH + LPL than that for ARH + APL [(19 ± 4) days vs. (21 ± 4) days, P = 0.000]. There were no significant difference in numbers of the pelvic lymph nodes resected, the extent of parametrial tissue, vaginal cuff, negative margins obtained and complications. The median follow-up was 32 months (range 4 to 105 months), there was no significant difference in the recurrence rate (7% vs. 5%, P = 0.540) and mortality rate (7% vs. 5%, P = 0.540), 5 years disease-free survival (90% vs. 94%, P = 0.812), 5 years over survival (90% vs. 95%, P = 0.532). There were not significant difference in quality of life between ARH + APL group and LRH + LPL group (P > 0.05). Only lympho-vascular space invasion was an independent prognostic factor by multivariate analysis (P = 0.016). CONCLUSIONS: For early-stage cervical cancer, LRH + LPL has similar outcomes compared with ARH + APL. Laparoscopic treatment by experienced surgeons should be an ideal alternative.

Identification of prognostic tumor-infiltrating immune cells in endometrial adenocarcinoma.

ABSTRACT: To identify prognostic tumor-infiltrating immune cells of endometrial adenocarcinoma.The gene expression profiles of endometrial adenocarcinoma were downloaded from the Cancer Genome Atlas (TCGA). The abundance of tumor-infiltrating immune cells in endometrial adenocarcinoma samples was calculated by CIBERSORT algorithm. Kaplan-Meier analysis was used to identify prognostic tumor-infiltrating immune cells.This study identified 22 kinds of tumor-infiltrating immune cells. Macrophages M0 and CD8 T cells were prognostic factors of endometrial adenocarcinoma. The abundance of macrophages M0 (P = .038) was significantly correlated with better prognosis of endometrial adenocarcinoma. In contrast, the abundance of CD8 T cells (P = .049) was associated with poor prognosis of endometrial adenocarcinoma.Tumor-infiltrati macrophages M0 and CD8 T cells were prognostic factors of endometrial adenocarcinoma.

Primary diaphragmatic closure following diaphragmatic resection and cardiophrenic lymph node dissection during interval debulking surgery for advanced ovarian malignancy.

•Gaining trans-diaphragmatic access to thoracic cavity during de-bulking laparotomy.•Assessment and dissection of bulky cardiophrenic lymph nodes to achieve optimal cytoreduction.•Technique for primary closure of diaphragm following radical resection.

Detection of high-risk human papillomavirus DNA in sentinel lymph nodes of patients with cervical cancer.

The aim of the present study was to investigate the expression of human papillomavirus (HPV) DNA in sentinel lymph nodes (SLN) in patients with early-stage cervical cancer (CC). In addition, the present study compared the positive rate of SLNs metastasis detected by routine pathological examination, and investigated the value of HPV-DNA in the detection of early CC lymph node micrometastasis. Reverse transcription-quantitative PCR (RT-qPCR) was used in order to evaluate the HPV DNA detection in all CC samples [International Federation of Gynecology and Obstetrics (FIGO) stage IA2-IIA2]. The consistency of HPV-DNA was compared between primary lesions and SLNs. The positive rates of HPV-DNA were compared with pathological diagnosis of SLN metastasis, and the association between the positive expression of HPV-DNA in SLNs and the clinical and pathological parameters of patients with cervical cancer were analyzed. A total of 345 sentinel lymph nodes were detected in 100 patients with IA2-IIA2 CC. The positive rates of RT-qPCR and conventional histopathological detection of SLNs metastasis were 31.6% (109/345) and 12.8% (44/345), respectively (P<0.001). The positive expression of HPV-DNA in SLNs was associated with the clinical stage and tumor diameter (P<0.05), but not with patients' age, depth of cervical invasion, histological grade, lymphatic and vascular space invasion (LVSI), squamous cell carcinoma antigen (SCCAg) (P>0.05). The detection of HPV-DNA expression in pelvic lymph nodes of early CC may be used to improve the detection rate of micrometastasis, guide the postoperative adjuvant therapy more accurately and improve prognosis. Patients with positive HPV-DNA would require closer surveillance than those with negative HPV-DNA.

Downregulation of microRNA-1246 inhibits tumor growth and promotes apoptosis of cervical cancer cells by targeting thrombospondin-2.

Cervical cancer pathogenesis is regulated by numerous factors, including microRNAs. MicroRNA 1246 (miR-1246) has been shown to serve a role in cervical cancer tumorigenesis. However, the mechanisms through which miR-1246 exerts its oncogenic effects are largely unknown. The aim of the current study was to evaluate the effects of lentivirus-mediated miR-1246 knockdown on the biological characteristics and behavior of cervical cancer cells, and to identify the downstream signaling pathways affected by miR-1246 knockdown. Short hairpins inhibiting miR-1246 were synthesized and cloned into a recombinant lentiviral vector (LV-miR-1246-Inh), which was then used to infect SiHa cervical cancer cells. The effects of LV-miR-1246-Inh infection on cell invasion, proliferation and apoptosis were evaluated by Transwell assay, Cell Counting Kit-8 assay and flow cytometry, respectively. Thrombospondin-2 (THBS2), matrix metalloproteinase 2 (MMP2), MMP9 and extracellular matrix (ECM) component expression levels were evaluated, and the growth of xenograft tumors formed following injection of SiHa cells with knockdown of miR-1246 was assessed. miR-1246 downregulation in SiHa cells decreased proliferation, induced apoptosis and upregulated THBS2 expression. Furthermore, MMP2 and MMP9 levels were downregulated, whereas components of the ECM were upregulated subsequent to miR-1246 knockdown, indicating that this miRNA regulates cervical cancer cell pathogenesis via the THBS2/MMP/ECM pathway. Notably, SiHa cells with miR-1246 downregulation had a markedly decreased ability to form tumors in vivo. These results suggest that miR-1246 functions during cervical cancer pathogenesis and tumor formation via the THBS2/MMP/ECM signaling pathway. These findings support the future use of miR-1246 suppression in the treatment of cervical cancer.

Prognostic significance of perineural invasion in vulvar squamous cell carcinoma.

Background: Perineural invasion (PNI) is closely associated with poor survival in several types of malignant tumours, but whether this is true in vulvar squamous cell carcinoma (VSCC) is unclear. The aims of this study were to determine the prognostic significance of PNI in patients with VSCC. Patients and methods: We retrospectively analysed clinico-pathological data on 105 patients with VSCC (stages IB-IV) treated surgically at our medical center between 2005 and 2015. Results: PNI was detected in 30 (28.6%) patients, and it was significantly associated with well-known clinical risk factors: large tumour size, depth of invasion, lymphatic vascular space invasion (LVSI), and intra- or extra-nodal spread. Significantly greater proportions of patients with PNI received adjuvant therapy after surgery (P=0.001) or showed local recurrence (P=0.002). Multivariable analysis indicated that risk factors for disease-free survival were tumour size (HR 3.02, 95%CI 1.75-7.75), LVSI (HR 4.82, 95%CI 1.36-17.07), depth of invasion (HR 3.11, 95%CI 1.50-6.44), lymph node metastasis (HR 3.15, 95%CI 1.14-8.96) and positive or close surgical margins (HR 4.86, 95%CI 1.67-14.19). The latter three variables were also risk factors for overall survival. PNI was associated with significantly shorter disease-free survival (DFS) (P=0.020) and overall survival (OS) (P=0.017) based on the log-rank test. Among patients who received adjuvant treatment, Kaplan-Meier curves indicated no significant differences between PNI-positive or -negative subgroups in disease-free survival (P=0.085) or overall survival (P=0.061). Based on multivariable analysis of all patients, PNI was not a significant risk factor for either type of survival . Conclusion: PNI in VSCC is associated with significantly shorter disease-free and overall survival, though it appears to be a weak independent predictor of worse prognosis. Combining PNI with other risk factors may be useful for predicting whether postoperative adjuvant therapy will be needed.

Prognostic genes in the tumor microenvironment in cervical squamous cell carcinoma.

Cervical squamous cell carcinoma (CSCC) is one of the most commonly occurring gynecological malignancies. Because CSCC is a biologically heterogeneous disease, its prognosis varies. Therefore, identifying prognostic biomarkers that reflect its biological heterogeneity could lead to better interventions for patients with a poor prognosis. This study used the ESTIMATE algorithm to identify immune related prognostic genes within the tumor microenvironment of CSCC. The results revealed that high immune scores were associated with better overall survival (P = 0.029). Differential expression analysis revealed 384 intersection genes influencing both the immune and stromal scores. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed the 384 intersection genes to be mainly enriched for T cell activation, the region of the membrane, carbohydrate binding, and cytokine-cytokine receptor interaction. Among them, 149 immune genes were predictive of overall survival in CSCC. These findings provide a more comprehensive understanding of immune genes within the tumor microenvironment as well as a list of immune genes prognostic in CSCC.

[Relationship between hormone therapy in women with ovarian malignancy and prognosis].

OBJECTIVE: To explore the relationship between hormone therapy (HT) in women with ovarian malignancy and prognosis. METHODS: HT was used in 31 patients with ovarian cancer after surgery, and 44 cases with ovarian cancer served as control. The expression of estrogen receptor (ER)alpha, ERbeta and progesterone receptor (PR) was detected by immunohistochemical staining respectively. The level of serum calcitonin and transforming growth factor alpha (TGFalpha) was detected by radio-immune and enzyme-linked immunosorbent assay pre- or post-surgery, as well as half a year to one year later post-surgery respectively in these cases. The survival curve of Kaplan-Meier and log-rank test as well as scale risk of Cox model were used to analyze the relationship between HT and prognosis of ovarian cancer. RESULTS: (1) The results of log-rank test showed that there was no difference in survival curve of patients with or without HT [(1108 +/- 52), (1086 +/- 43) d; P = 0.940]; the results of scale risk of Cox model also showed that HT was not an independent prognosis factor for patients with HT. (2) There was no relationship with HT and the accumulated survival in patients with either positive or negative expression of ERalpha, ERbeta and PR in tissue; as well as between HT and the level of serum TGFalpha pre-, post-surgery, or half a year to one year after surgery. (3) The level of serum calcitonin in patients without HT post-surgery half a year to one year later was higher than that pre-surgery [(141 +/- 13), (95 +/- 11) microg/L; P < 0.05], but there was no significant difference between patients with HT half a year to one year later post-surgery and pre-surgery [(90 +/- 18) microg/L, (93 +/- 14) microg/L; P > 0.05]. (4) There was a significant difference in body and emotion function between HT and without HT groups [(1.84 +/- 1.50), (1.45 +/- 0.82); (12.69 +/- 10.20), (12.90 +/- 11.61); P < 0.05], as well as in sex quality and autonomic nerve maladjustment and in the special list made [(1.05 +/- 0.74), (1.77 +/- 1.08); (10.10 +/- 3.21), (13.09 +/- 4.30); P < 0.05]. CONCLUSIONS: There is no adverse influence on prognosis in using of HT for patients with ovarian cancer after surgery. HT for patients with ovarian cancer post-surgery can help keep a stable level of serum calcitonin as well as improve the quality of life.

Indocyanine green angiography for preserving the ureteral branch of the uterine artery during radical hysterectomy: Two case report.

RATIONALE: Conventional radical hysterectomy is frequently associated with postoperative ureteral ischemic necrosis, urinary fistula, stenosis, and kidney seeper. Some have suggested that preserving the ureteral branch during radical hysterectomy may reduce the incidence of ureteral complications. However, the feasibility of such preservation has not been explored using intraoperative imaging techniques. PATIENT CONCERNS: Two cervical cancer patients aged 45 and 53 years were selected to undergo surgery in our hospital in October 2017. Both patients showed normal function of major organs and no special treatment was deemed necessary based on their subjective symptoms and preoperative examination. DIAGNOSES: Both patients were diagnosed with cervical cancer in stage Ib1 according to the staging scheme of the International Federation of Gynecology and Obstetrics (FIGO 2009). INTERVENTIONS: Two patients underwent ureteral branch-sparing radical hysterectomy. During surgery, indocyanine green (ICG) fluorescence angiography was used to identify the ureteral branch and evaluate perfusion of the uterine artery, its ureteral branch and the ureter. OUTCOMES: The uterine artery and ureteral branch were clearly labeled by green fluorescence, as were the distal serous layer of the ureter and tissue supplied by the ureteral branch. During 4-month follow-up, neither patient suffered hydronephrosis, ureteral fistula or stricture. LESSONS: ICG angiography is a useful intraoperative imaging technique for identifying the ureteral branch and evaluating the branch-sparing surgery. Based on real-time angiography, sparing the ureteral branch can maintain blood supply to the ureter distal serous layer and neighboring tissues.

[Relationship between combined multigene detection and response to chemotherapy and prognosis in epithelial ovarian carcinomas].

OBJECTIVE: To evaluate the relationship between combined multigene detection and response to chemotherapy and prognosis in epithelial ovarian carcinomas (EOCS). METHODS: A total of 80 ovarian tissue samples taken from the surgical specimens of patients with EOCS of our hospital in the last two decades who had received chemotherapy after surgery were paraffin-embedded. The samples were divided into 2 groups, good prognosis group (patients who survived more than 2 years, n = 46) and poor prognosis group (patients who survived less than 2 years, n = 34). The expression levels of ToPo-II, Ki-67, MGMT, PCNA, p27, p53, p16, P-gp, LRP, GST-pi, bcl-2, C-myc, Fas, bax, MSH2, MRP and BCRP were investigated by the combination of tissue arrays and immunohistochemical streptavidin-biotin peroxidase (SP) method in all samples. Data were analysed with SPSS 12.0 for windows. RESULTS: There were statistically significant differences in the positive expression levels of P-gp, BCRP, MGMT, MSH2, p27 and p16 (62%, 50% and 50% in poor prognosis group vs 33%, 28% and 28% respectively, P < 0.05) in the good prognosis group, suggesting that the positive expression levels of P-gp, BCRP, MGMT, MSH2, p27 and p16 were related to the response to chemotherapy and prognosis in EOCS. And the positive expression of P-gp, BCRP and MSH2 (43%, 54% and 43%) indicated poor prognosis, while the positive expression of MGMT, p27 and p16 (18%, 29% and 24%, P < 0.05) indicated good prognosis. Cox multigene expression analysis confirmed that the positive expression levels of MRP, C-myc, LRP, p16, p27, MGMT, ToPo-II, P-gp and GST-pi were related to the response to chemotherapy and prognosis in EOCS. And the positive expression of MRP, C-myc, LRP, ToPo-II, P-gp and GST-pi indicated poor prognosis, while the positive expression of MGMT, p27 and p16 indicated good prognosis. Combined multigene detections were conducted among P-gp, BCRP, MGMT, MSH2, p27 and p16, and there were statistically significant differences in the positive coexpression of P-gp plus MGMT in the two groups (P < 0.05); indicating that the combined multigene expression were related to the response to chemotherapy and prognosis in EOCS. The predictive value to response to chemotherapy and prognosis of the positive coexpression of P-gp plus MGMT was 70%. CONCLUSIONS: By univariate and multivariate analyses, the positive expression of P-gp, MGMT, p27 and p16 are related to the response to chemotherapy and prognosis in EOCS. The combined multigene expression of P-gp plus MGMT are related to the response to chemotherapy and prognosis and could predict prognosis more effectively.

Application of carbon nanoparticles in laparoscopic sentinel lymph node detection in patients with early-stage cervical cancer.

OBJECTIVE: To investigate the value of carbon nanoparticles in identifying sentinel lymph nodes in early-stage cervical cancer. METHODS: From January 2014 to January 2016, 40 patients with cervical cancer stage IA2-IIA, based on the International Federation of Gynecology and Obstetrics (FIGO) 2009 criteria, were included in this study. The normal cervix around the tumor was injected with a total of 1 mL of carbon nanoparticles (CNP)at 3 and 9 o'clock. All patients then underwent laparoscopic pelvic lymph node dissection and radical hysterectomy. The black-dyed sentinel lymph nodes were removed for routine pathological examination and immunohistochemical staining. RESULTS: Among the 40 patients, 38 patients had at least one sentinel lymph node (SLN). The detection rate was 95% (38/40). One hundred seventy-three SLNs were detected with an average of 3.9 SLNs per side. 25 positive lymph nodes, which included 21 positive SLNs, were detected in 8 (20%) patients. Sentinel lymph nodes were localized in the obturator (47.97%), internal lilac (13.87%), external lilac (26.59%), parametrial (1.16%), and common iliac (8.67%) regions. The sensitivity of the SLN detection was 100% (5/5), the accuracy was 97.37% (37/38), and the negative predictive value was 100. 0% and the false negative rate was 0%. CONCLUSIONS: Sentinel lymph nodes can be used to accurately predict the pathological state of pelvic lymph nodes in early cervical cancer. The detection rates and accuracy of sentinel lymph node were high. Carbon nanoparticles can be used to trace the sentinel lymph node in early cervical cancer.

[The mouse ovarian surface epithelium cells (MOSE) transformation induced by c-myc/K-ras in].

OBJECTIVE: To study the function of c-myc and K-ras in tumorigenesis of ovarian cancer. METHODS: K-ras and/or c-myc cDNAs were introduced into mouse ovarian surface epithelium cells (MOSE) using recombinant Moloney retroviral vectors. The resulting MOSE cells were studied by cell proliferation assays, the ability to form colonies in soft agarose, matrigel invasion assays and tumorigenicity assays in nude mice. RESULTS: K-ras and c-myc can be easily delivered to the normal MOSE cells by recombinant retroviruses. mRNA and protein of the target genes can be detected by RT-PCR and Western blot. Cell proliferation assays showed that MOSE-Ras cells and MOSE-RM cells (MOSE-Ras/Myc) grew more rapidly than parental cells (MOSE) and MOSE-Myc cells (P <0.01). In addtition, MOSE-RM cells grew more rapidly than MOSE-Ras cells (P <0. 05). Cell colony formation assays showed that while MOSE-Ras and MOSE-RM cells can form colonies in soft-agarose, the MOSE-Myc and MOSE cells did not. Matrigel invasion assays showed that MOSE-Ras and MOSE-RM cells have invasion ability, but not MOSE-Myc ascites and the control MOSE cells. Xenograft experiments showed that MOSE-Ras and MOSE-RM cells were able to form tumors in nude mice following intraperitoneal injection. Tumors were not observed in animals injected with either MOSE-Myc or MOSE cells. CONCLUSION: The recombinant Moloney retroviral system is a highly efficient and convenient method for introducing and expressing foreign genes in murine surface epithelial cell cultures. In this model, expression of K-ras alone is sufficient to generate tumorigenic MOSE, however expression of c-myc in conjunction with K-ras results in cells with a higher index of malignancy. Based on the assays described in this report, expression of c-myc alone can not transform MOSE cultures although it does play a role in cooperation with K-ras.

[*OPCML gene transferred by recombinant lentiviruses in vitro and its inhibition to ovarian cancer cells].

OBJECTIVE: To study the inhibition of OPCML on ovarian cancer cell lines using a lentiviral vector system for efficient gene transduction. METHODS: The murine OPCML cDNA was amplified by PCR from CD1 murine brain cDNA using gene specific primers, and subcloned into the lentiviral vector, pWPI-GFP, to generate the lentiviral expression vector, pWPI-OPCML. Recombinant lentiviruses were produced by 293T cells following the co-transfection of pWPI-OPCML, with the packaging plasmids pCMV-dR8.74 and pMDG. The resulting recombinant lentiviruses which carried OPCML or control viruses (only carrying GFP), were then used to infect the human ovarian cancer cell lines A2780 and OCC1 in addition to normal CD1 mouse ovarian surface epithelial cells. The infected cells were then characterized by cell proliferation assays, cell aggregation assays, cell cycle analysis by flow cytometry and tumorigenicity assays following injection into nude mice. RESULTS: (1) The efficiency of infection of the cell lines using the lentiviral vectors was almost 100% allowing the stable expression of OPCML in nearly all cells. Stable expression of OPCML (60 000) and GFP (27 000) proteins was confirmed by western blot analysis. (2) A2780 cells expressing OPCML [(7.6 +/- 1.0) x 10(5)] grew slowly compared to A2780 parental [(20.0 +/- 2.6) x 10(5)] or control virus infected cells [(18.1 +/- 1.7) x 10(5), P < 0.01], but the expression of OPCML had no effect on the proliferation rates of OCC1 and the normal CD1 cells when compared to their respective parental or controls (P > 0.05). (3) Flow cytometry based cell cycle assays showed that the expression of OPCML could arrest A2780 cells (G(0) approximately G(1) 67% vs 75%, P < 0.05); but not OCC1, CD1 cells. (4) The rate of aggregation of single cell suspensions was measured and found to be increased in all cell lines expressing OPCML indicating the increased cell surface adhesion mediated by OPCML. (5) A2780 cells expressing OPCML only formed a single tumor in 1/4 mice (10 mg) which was significantly smaller than controls [4/4; A2780 (280 +/- 53) mg and A2780/pWPI (677 +/- 323) mg; P < 0.01]. Expression of OPCML in tumor was confirmed by immunohistochemistry. CONCLUSIONS: The use of lentiviral vectors allowed the efficient expression of OPCML in nearly 100% of target cells. Expression of the OPCML cDNA resulted in an increase of cell adhesion in all cell lines tested, and decreased the proliferation and tumorigenicity of the A2780 ovarian cancer cell line. This indicates that the OPCML may be a new tumor suppressor gene.

Evaluation of the association between perineural invasion and clinical and histopathological features of cervical cancer.

Perineural invasion (PNI) has been investigated as a new prognostic factor in a number of carcinomas. However, studies on PNI in cervical cancer are limited, and inconsistent conclusions have been reported by different groups. The aim of the present study was to analyze the relationship between perineural invasion (PNI) and clinical and histopathological features of cervical cancer, and to evaluate the clinical significance of PNI of cervical cancer. Retrospective review identified 206 patients with cervical cancer who underwent radical hysterectomy plus pelvic lymphadenectomy between December 2012 and August 2014. The association between PNI and clinical and histopathological features of cervical cancer and post-operative radiotherapy was evaluated based on univariate and multivariate analyses. PNI of cervical cancer was identified in 33 of 206 (16%) cervical cancer patients. Univariate analysis demonstrated that PNI was associated with clinical stage, tumor grade, tumor size, depth of invasion, lymphovascular space invasion (LVSI), and lymph node metastasis (P<0.05), but not associated with age and histopathological types (P>0.05). Multivariate analysis suggests that LVSI and lymph node metastasis were associated with PNI of cervical cancer (P<0.05). In addition, post-operative radiotherapy was significantly more recommended for patients with PNI than those without PNI (P<0.001). In conclusion, PNI of cervical cancer is associated with LVSI and lymph node metastasis and can be used as an index for the determination of post-operative radiotherapy for cervical cancer patients.

Models of ovarian cancer--are we there yet?

Ovarian cancer is the most lethal of all gynecological cancers and arises most commonly from the surface epithelium. Successful clinical management of patients with epithelial ovarian cancer is limited by the lack of a reliable and specific method for early detection, and the frequent recurrence of chemoresistant disease. Experimental models are of crucial importance not only to understand the biological and genetic factors that influence the phenotypic characteristics of the disease but also to utilize as a basis for developing rational intervention strategies. Ovarian cancer cell lines derived from ascites or primary ovarian tumors have been used extensively and can be very effective for studying the processes controlling growth regulation and chemosensitivity or evaluating novel therapeutics, both in vitro and in xenograft models. While our limited knowledge of the initiating events of ovarian cancer has restricted the development of models in which the early pathogenic events can be studied, recent advances in the ability to manipulate gene expression in ovarian surface epithelial cells in vitro and in vivo have begun to provide insights into the molecular changes that may contribute to the development of ovarian cancer. This review highlights the strengths and weaknesses of some of the current models of ovarian cancer, with special consideration of the recent progress in modeling ovarian cancer using genetically engineered mice.

Systematic review of laparoscopic comprehensive staging surgery in early stage ovarian cancer: a meta-analysis.

OBJECTIVE: To assess the clinical outcomes of laparoscopic comprehensive staging surgery in early stage ovarian cancer. MATERIALS AND METHODS: Electronic literature searches were conducted in Embase, MEDLINE, Cochrane Library, China Biology Medicine, and Chinese National Knowledge Infrastructure, and literature on laparoscopy versus laparotomy for comprehensive staging surgery was retrieved. The literature was selected according to certain inclusion criteria. Data were extracted from these studies and the quality of the included studies was assessed. The meta-analysis was conducted using the Review Manager 5.2 software. RESULTS: A total of 11 nonrandomized controlled trials involving 591 cases were included. The pooled data indicated less intraoperative blood loss, lower postoperative complication rates, shorter postoperative hospital stays, and lower postoperative recurrence rates in the laparoscopy group. There were no significant differences in operative time, harvested lymph node number, intraoperative complications, or mortality. CONCLUSION: For comprehensive staging surgery, laparoscopy was equivalent to or even better than conventional laparotomy for early ovarian cancer. More robust evidence should be explored for precise verification.

Feasibility and Safety of Video Endoscopic Inguinal Lymphadenectomy in Vulvar Cancer: A Systematic Review.

OBJECTIVE: To systematically review previous studies and to evaluate the feasibility and safety of video endoscopic inguinal lymphadenectomy (VEIL) in vulvar cancer. METHODS: We conducted a comprehensive review of studies published through September 2014 to retrieve all relevant articles. The PubMed, EMBASE, Web of Science, Cochrane Library, Wan Fang Data and Chinese National Knowledge Infrastructure databases were systematically searched for all relevant studies published in English or Chinese through September 2014. Data were abstracted independently by two reviewers, and any differences were resolved by consensus. RESULTS: A total of 9 studies containing 249 VEIL procedures involving 138 patients were reviewed. Of the 249 VEIL procedures, only 1 (0.4%) was converted to an open procedure for suturing because of injury to the femoral vein. The range of operative time was 62 to 110 minutes, and the range of estimated blood loss was 5.5 to 22 ml. The range of the number of harvested lymph nodes was 7.3 to 16. The length of hospital stay varied from 7 to 13.6 days across reports. The incidence of lymph node metastasis was 19.7% (27/138), and the recurrence rate was 4.3% (3/70) within 3 to 41 months of follow-up. One or more short-term complications were documented in 18 of 138 (13.0%) patients. Complications after VEIL were observed in 14 (10.13%) patients and in 15 (6.0%) of the VEIL cases, including major lymphocyst formation in 9 (3.6%), lymphorrhea in 2 (0.8%), inguinal wound infection without wound breakdown in 3 (1.2%) and lymphedema in 1 (0.4%). CONCLUSIONS: VEIL appears to be a feasible procedure in the management of vulvar cancer. There may be potential benefits that result in lower morbidity compared to traditional methods, but this has yet to be objectively proven.