Effects of SQLE gene on proliferation, apoptosis, migration and invasion of squamous cervical cancer cells / 中国药理学通报

Aim To explore the effect of squalene ep-oxidase ( SQLE) in cervical squamous cell carcinoma and the molecular mechanism. Methods Firstly, the gene expression profiling interactive analysis (GEPIA) database was used to analyze the mRNA expression of SQLE in cervical squamous cell carcinoma and normal cervical tissues, and the human protein atlas ( HPA) database was used to obtain the expression of SQLE protein in cervical squamous cell carcinoma and normal cervical tissues. We researched the correlation between SQLE gene and the clinicopathological characteristics of cervical squamous cell carcinoma through UALCAN database. Then GEPIA database was utilized to evaluate the overall survival (OS) and disease free survival (DFS) of cervical squamous cell carcinoma patients with high expression of SQLE mRNA. Finally, Siha cells were taken as the research object, and the effects of SQLE gene on proliferation, apoptosis, migration and invasion of Siha cells were observed by using small interfering RNA ( siRNA) to inhibit the expression of SQLE gene and transfecting recombinant plasmid to promote the expression of SQLE gene. The mRNA expression of SQLE was assessed by qPT-PCR. Bax, Bcl-2, Vimentin, E-cadherin, PI3K, Akt, p-PI3K and p-Akt protein expression levels were examined by Western blot. Results The mRNA expression and protein expression of SQLE in cervical squamous cell carcinoma was higher than that in normal tissues (P < 0. 05 ), and the OS of patients with high expression of SQLE mRNA was significantly shortened in cervical squamous cell carcinoma ( P < 0. 05 ). The expression of SQLE in stage IV of cervical squamous cell carcinoma was significantly higher than that in stage I, II and III (P < 0. 01). And the expression of SQLE in lymph node metastasis Nl group was markedly higher than that in NO group ( P < 0. 01 ). Cell experiments showed that interference with SQLE could significantly inhibit the proliferation, migration and invasion of Siha cells, and promote their apoptosis (P < 0. 01 ). The trend was opposite when SQLE was overexpressed. SQLE knockdown decreased the protein expression levels of Bcl-2, Vimentin, p-PI3K and p-Akt, increased the protein expression levels of Bax and E-cadherin, and the ratio of Bcl-2/Bax decreased significantly (P < 0. 05, P < 0. 01 ) . The trend was opposite when SQLE was overexpressed. Conclusions SQLE is highly expressed in human cervical squamous cell carcinoma. SQLE may induce Siha cell proliferation, migration, invasion, and inhibit their apoptosis by regulating PDK/Akt signaling pathway.

Effects of miR-9-5p on the migration, invasion and epithelial-mesenchymal transition process in cervical squamous cell carcinoma / 中南大学学报(医学版)

OBJECTIVES@#Cervical squamous cell carcinoma is the most common cancer in female reproductive system. This study aims to explore the effect of microRNA-9-5p (miR-9-5p) on the migration, invasion, and epithelial-mesenchymal transition (EMT) process of cervical squamous cells.@*METHODS@#Bioinformatics were used to predict the miRNAs that could bind to E-cadherin (E-cad). The Cancer Genome Atlas (TCGA) database was used to analyze and extract significantly differentially expressed miRNAs from part of cervical squamous cell carcinoma tissues and normal cervical tissues, and miR-9-5p was selected as the main research target. The translated regions (UTR) of wild-type E-cad (E-cad-WT 3'-UTR) or the 3'-UTR of mutant E-cad (E-Cad-MUT 3'-UTR) was transfected with miR-9-5p mimic normal control (NC), and miR-9-5p mimic was co-transfected human embryonic kidney cells (293T). The relationship between miR-9-5p and E-cad was detected by double luciferase assay. The expression of miR-9-5p in normal cervical epithelial cell lines (H8) and cervical squamous cell lines (C33A, siha, caski and Me180) were detected by quantitative real-time PCR. Then, the experiments were divided into groups as follows: a block control group, an overexpression control group (mimic-NC group), a miR-95p overexpression group (mimic group), an inhibitory expression control group (inhibitor-NC group), and a miR-9-5p inhibitory expression group (inhibitor group). The changes of migration ability were detected by scratch assay. Transwell invasion assay was used to analyze the changes of invasion ability, and the mRNA and protein changes of E-cad and vimentin were detected by quantitative real-time PCR and Western blotting.@*RESULTS@#MiR-9-5p had a targeting binding relationship with E-cad. Compared with the normal cervical tissue H8 cell line, the miR-9-5p was highly expressed in cervical cancer cell lines (C33A, siha, caski and Me180) (all P<0.05). The luciferase activity of E-cad-MUT was increased compared with that of E-cad-WT in miR-9-5p mimic cells (P<0.05). Compared with the blank control group, the protein and mRNA expressions of E-cad were decreased in the miR-9-5p mimic group (both P<0.05), which were increased in the miR-9-5p inhibitor group (both P<0.05). Compared with H8 cell line, the miR-9-5p was highly expressed in the cervical squamous cell lines (all P<0.05). Compared with the mimic-NC group, the distance of wound healing, the number of caski and Me180 cells invaded below the membrane, and the mRNA and protein expressions of vimentin were all increased in the miR-9-5p mimic group (all P<0.05), while the mRNA and protein of E-cad were decreased (both P<0.05). Compared with the inhibitor-NC group, the distance of wound healing, the number of caski and Me180 cells invading the membrane, and the mRNA and protein expressions of vimentin were decreased in the miR-9-5p inhibitor group (all P<0.05), but the mRNA and protein expressions of E-cad were increased (both P<0.05).@*CONCLUSIONS@#The miR-9-5p is highly expressed in cervical squamous cell carcinoma, which can increase the migration and invasion ability, and promote the EMT process of cancer cells.

Correlation and clinical significance of VISTA expression and cervical squamous cell carcinoma / 中华肿瘤杂志

Objective: To explore the relationship between the expression of the T-cell activation suppressor-immunoglobulin variable region (VISTA) and the development of cervical squamous cell carcinoma (CSCC), and the impact on the prognosis of CSCC patients. Methods: Cervical tissue samples from 116 CSCC, including 23 cervical intraepithelial neoplasia (CIN) grade I, 23 CIN grade Ⅱ-Ⅲ, and 23 chronic cervicitis patients, were collected from the First Hospital of Soochow University between March 2014 and April 2019. The expression of VISTA in each group was detected by immunohistochemistry (IHC). Survival data of CSCC patients were obtained by follow-up. The survival analysis was performed by Kaplan-Meier method, and survival differences between groups were compared by Log rank test. Prognostic impact factors were analyzed using a multifactorial Cox proportional hazards model. Results: The positive rate of VISTA expression in CSCC group was 32.8% (38/116), and which of grade Ⅱ-Ⅲ was 17.4% (4/23). VISTA expression results showed no positive expression patients in the cervical intraepithelial neoplasia grade I and chronic cervicitis groups. The differences between the CSCC group and other groups were statistically significant (P<0.01). In 116 CSCC patients, VISTA expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis (P<0.01). The mean survival time of patients in the VISTA positive expression group was 30.7 months, and the 3-year survival rate was 44.7% (17/38). However, the mean survival time of the patients in the VISTA negative expression group was 49.1 months, and the 3-year survival rate was 87.2% (68/78). The Cox regression model found that VISTA expression positivity (P=0.001) and FIGO stage (P=0.047) were prognostic factors for CSCC, and patients with VISTA-positive CSCC had a 4.130-fold risk of death higher than those with VISTA-negative expression. Conclusions: The VISTA protein is highly expressed in CSCC tissues, and its expression level is closely related to the occurrence and development of CSCC. The expression of VISTA can be used as an independent predictor of CSCC prognosis and can provide a strong basis for the treatment of CSCC with immune checkpoint inhibitors.

Prognosis of Stage ⅠB-ⅡA Cervical Squamous Cell Carcinoma Patients with Intermediate Risk Factors Treated with Adjuvant Chemotherapy Versus Concurrent Chemoradiotherapy: A Prospective Randomized Controlled Trial / 肿瘤防治研究

Objective To compare the prognosis of stage ⅠB-ⅡA cervical squamous cell carcinoma patients with intermediate risk factrs between adjuvant chemotherapy and concurrent chemoradiotherapy, and to explore the safety and effectiveness of adjuvant chemotherapy after surgery. Methods A total of 190 patients treated at the Affiliated Cancer Hospital of Guangxi Medical University were selected and randomly divided into two groups: chemotherapy group (CT group, n=95) and concurrent chemoradiotherapy group (CCRT group, n=95). Ten patients lost to follow-up. Kaplan-Meier method and Log rank test were used for OS calculation and survival curve comparison. Cox proportional-hazards regression model was used for multivariate analysis. Results After a median follow-up of 36.7 months, 190 patients were evaluable. The incidence of G3/G4 blood system toxicity were 3.3% in CT group and 10.11% in CCRT group (P=0.019), the incidence of severe gastrointestinal toxicity were 4.4% in CT group and 17.98% in CCRT group, the incidence of radiation-related response was 22.48%. There was no significant difference in the local recurrence rate or distant recurrence rate between two groups (P > 0.05). There was no statistically significant difference in PFS and OS between two groups (P > 0.05). Conclusion There is no significant difference between postoperative chemotherapy and concurrent chemoradiotherapy on stage ⅠB-ⅡA cervical squamous cell carcinoma patients with intermediate risk facfors, but the adverse reactions of postoperative chemotherapy are significantly reduced compared with concurrent chemoradiotherapy.

Mechanism of matrine inhibiting proliferation of cervical squamous carcinoma cells by up-regulating LncRNA BDNF-AS / 中草药

Objective: To investigate the mechanism of matrine inhibiting the proliferation of cervical squamous cancer cells. Methods: CCK-8 method was used to detect the effect of matrine on the survival rate of SiHa and C33A cells, and flow cytometry was used to detect cell cycle. High throughput sequencing technology was used to screen the differentially expressed genes between control cells and cells being treated with matrine. qRT-PCR and Western blotting method were used to detect the expression of BDNF-AS and BDNF in cervical squamous cancer cells and allograft tumor tissue. A total of 32 cases of cervical squamous cell carcinoma tissues were collected in the Second People’s Hospital of Nanyang from March 2013 to December 2016. qRT-PCR was used to detect the expression of BDNF-AS in cervical squamous cell carcinoma tissues of these cases. Results: Matrine significantly inhibited the proliferation of cervical squamous carcinoma cells. A total of 924 differentially expressed genes were screened out from cervical squamous carcinoma cells before and after being treated with matrine, 637 (68.9%) were up-regulated while 287 (31.1%) were down-regulated. Matrine up-regulated the expression of BDNF-AS. The expression of BDNF-AS was negative correlated with the degree of pathological differentiation and clinical stage (P < 0.05). BDNF-AS expression in tissues was associated with survival of patients with cervical squamous cell carcinoma. Multivariate analyses suggested the expression of BDNF-AS was served as an independent predictor for overall survival. Conclusion: BDNF-AS may be a tumor suppressor in the tumorigenesis and tumor progression of cervical squamous cell carcinoma. Matrine may inhibit the proliferation of cervical squamous carcinoma cells by up-regulating the expression of BDNF-AS.

Salidroside affects proliferation, invasion and apoptosis of cervical squamous cell carcinoma C33Acells through JAK2/STAT3 pathway / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effects of salidroside on the proliferation, invasion and apoptosis of cervical squamous cell carcinoma C33A cells and explore its possible mechanism. Methods: C33A cells were divided into 4 groups: control group, low-dose group (salidroside 50 μg/mL), high-dose group (salidroside 150 μg/mL), and AG490 group (inhibitor of JAK2/STAT3 signaling pathway, 50 μmol/L). Effects of salidroside and AG490 on the proliferation, invasion and apoptosis of C33A cells were detected by MTT method, EdU labeling experiment, Transwell assay, Rh123 staining and Flow cytometry, respectively. Western blotting was used to detect the effects of salidroside and AG490 on the expressions of JAK2/STAT3 pathway-related proteins (p-JAK2, p-STAT3) and apoptosis-related proteins (Bax, Bcl-2, caspase-3) in C33A cells. Result: Compared with the control group, the proliferation and DNA synthesis as well as the invasion of C33Acells in the low-dose group were significantly inhibited (all P<0.05), while the apoptosis was significantly enhanced (P<0.05); in the meanwhile, the fluorescence intensity of Rh123 was significantly reduced (all P<0.05) and the membrane structure of C33A cells were destroyed; moreover, the expressions of p-JAK2, p-STAT3 and Bcl-2 were significantly decreased while the expressions of Bax and caspase-3 were significantly increased (all P<0.05). Compared with the low-dose group, the effects of high-dose salidroside and AG490 on the proliferation, invasion, apoptosis and related protein expressions in C33A cells were more significant (all P<0.05), but there was no difference between the high-dose group and the AG490 group. Conclusion: Salidroside can inhibit the proliferation and invasion of C33A cells and promote cell apoptosis. Its mechanism may be related to inhibition of JAK2/ STAT3 signaling pathway.

Analysis of vaginal elimination combined with radiotherapy and chemotherapy for giant stage IIIB cervical squamous cell carcinoma / 中国肿瘤临床

Objective: To assess the efficacy and safety of vaginal elimination in the treatment of giant stage IIIB cervical squamous cell carcinoma (SCC). Methods: From January 2016 to June 2017, clinical data of 49 patients with giant stage IIIB cervical SCC in Chongqing University Cancer Hospital were retrospectively analyzed. Survival and influencing factors were analyzed using the Kaplan-Meier method and multivariable Cox model. Results: After a median 36.0-month follow-up, the complete remission, local recurrence, and distant metastasis rates were 83.7% (41/49), 4.1% (2/49), and 34.7% (17/49), respectively. The overall survival (OS) rate, disease-free survival rate, distant metastasis-free survival (DMFS) rate, and local control rate (LCR) were 76.6%, 26.7%, 26.7%, and 77.8%, respectively. The occurrence rates of acute grade 3-4 adverse hematological events, diarrhea, frequency of urination, late grades 3-4 adverse rectitis events, and cystitis were 40.82% (20/49), 20.41% (10/49), 6.12% (3/49), 20.41% (10/49), and 8.16% (4/49), respectively. Cox analysis showed that the duration of radiotherapy affected OS and LCR (P<0.05), the dose of EQD2 affected DMFS and LCR (P<0.05), and the recurrence rate of SCC that persisted despite concurrent radiotherapy and chemotherapy was 61% (11/18). Conclusions: Patients with giant stage IIIB cervical SCC benefit from vaginal elimination combined with radiotherapy and chemotherapy; however, adverse reactions in the rectum and bladder increase, and thus, individualized treatment is recommended. The duration of radiotherapy is an independent factor for the prognosis of cervical cancer. SCC can be used for follow-up and monitoring cervical cancer recurrence.

Expression of miR-760 in cervical squamous cell carcinoma tissues and cells and its effect on malignant biological behaviors of SiHa cells / 中国肿瘤生物治疗杂志

@#Objective: To investigate the expression of microRNA(miR) -760 in human cervical squamous cell carcinoma (CSCC) tissues and cells, and it’s effects on the proliferation, apoptosis, invasion, migration and epithelial-mesenchymal transition (EMT) of SiHa cells, as well as its molecular mechanism. Methods: Eighty pairs of CSCC cancerous and corresponding para-cancerous tissue specimens which were pathologically confirmed and 40 cases of normal cervical tissue specimens obtained by myomectomy in Liaocheng Maternal and Child Health Hospital of Shandong Province from April 2015 to August 2018 were selected. The expression of miR-760 in CSCC tissues, para-cancerous tissues and normal cervical tissues, human CSCC cell lines (SiHa, HCC94) and human cervical squamous epithelial immortalized H8 cells were detected by qPCR, and the relationship between miR-760 and clinicopathological characteristics of CSCC patients was analyzed. miR-760 mimics and NC-mimics plasmids were transfected into SiHa cells by liposome transfection. The expression of miR-760 in SiHa cells was detected by qPCR, the proliferation activity and apoptosis rate were detected by CCK-8 test and flow cytometry, respectively. The invasion and migration of SiHa cells were detected by Transwell assay. The expressions of EMT-related proteins, such as E-cadherin, vimentin and N-cadherin, in SiHa cells were detected by WB. Bioinformatics was used to predict the targeting relationship between FOXA1 and miR-760, and double luciferase reporter gene assay was used to verify the direct regulation of miR-760 on FOXA1. Results: The expression of miR-760 in CSCC tissues was significantly lower than that in para-cancerous tissues and normal cervical tissues (all P<0.01), and the expression of miR-760 was closely related to lymphnode metastasis and clinical stage (all P<0.01). The expression of miR-760 in SiHa and HCC94 cells was significantly lower than that in H8 cells (all P<0.01). Up-regulation of the expression of miR-760 could significantly inhibit the proliferation, invasion and migration of SiHa cells (all P<0.01), promote apoptosis (P<0.01), up-regulate the expression of E-cadherin protein (P<0.01), and down-regulate the protein expressions of vimentin and N-cadherin (all P<0.01).FOXA1 was a direct target gene of miR-760 (P<0.01). Up-regulation of miR760 significantly inhibited the mRNA and protein expressions of FOXA1 in SiHa cells (all P<0.05). Conclusion: The expression of miR-760 is down-regulated in CSCC tissues and cells, and it can regulate the proliferation, invasion, migration and apoptosis of CSCC cells by targeting FOXA1. ··

Clinical Effect of Laparoscopic Radical Hysterectomy on Cervical Squamous Cell Carcinoma / 中国医科大学学报

Objective To evaluate the clinical efficacy of laparoscopic radical hysterectomy and pelvic lymph node dissection (PLND) in cervical squamous cell carcinoma (CSCC). Methods The clinical data of 83 CSCC patients in our hospital were retrospectively analyzed. The open surgery group (n = 43) underwent traditional transabdominal radical hysterectomy and PLND, while the laparoscopy group (n = 40) underwent laparoscopic radical hysterectomy and PLND. Intraoperative and postoperative indices were compared between the two groups. Results The intraoperative bleeding volume in stage ⅠB1 and ⅡAl patients in the open surgery group was greater than in the laparoscopy group. The operative duration was shorter and fewer lymph nodes were dissected in the open surgery group than in the laparoscopy group (P ＜ 0.05). The time to flatus, fever duration, and hospital stay in stage ⅠB1 and ⅡA1 patients in the open surgery group were longer than in the laparoscopy group (P ＜ 0.05). The frequency of painkiller use in stage ⅡA1 patients in the open surgery group was greater than in the laparoscopy group (P ＜ 0.05). There was no statistical difference in the incidence of intraoperative and postoperative complications between the ⅠB1 and ⅡA1 groups (P＞ 0.05). The physical fitness and social function scores and the adverse effects were significantly different in the open surgery group from those in the laparoscopy group (P ＜ 0.05). Conclusion Laparoscopic radical hysterectomy and PLND for CSCC can reduce intraoperative bleeding volume, increase the number of lymph nodes dissected, shorten the fever duration and hospital stay, and increase the quality of life.

Effect evaluation of the low-dose hormone replacement therapy on menopausal-related symptoms of young patients with cervical squamous cell carcinoma / 预防医学

Objective@#To evaluate the effect of low-dose hormone replacement therapy（HRT）on menopausal-related symptoms in young patients with cervical squamous cell carcinoma.@*Methods@#From March 2016 to September 2018,eighty patients aged 45 years below with cervical squamous cell carcinoma of stage Ⅰ-Ⅱ and iatrogenic menopause were recruited,who were diagnosed at Zhejiang Cancer Hospital and Women's Hospital Affiliated to Medical College of Zhejiang University. Fourty of them performed low dose HRT（1 mg estradiol valerate a day or 1.25 mg tibolone a day）,twenty performed standard dose HRT（1 mg estradiol valerate and 1.25 mg tibolone a day）,another twenty do not perform HRT as a control group. The levels of follicle stimulating hormone（FSH）,estradiol（E2）,menopausal symptoms（the improved Kupperman score）and incidence of side effects were assessed before and 1,3,6 months after the intervention. @*Results@#There were significant differences in E2 levels,FSH levels and improved Kupperman scores among the low dose group,the standard dose group and the control group（all P<0.05）. With the extension of intervention time,E2 levels in the low dose group and the standard dose group increased first and then decreased,FSH levels and improved Kupperman scores decreased（all P<0.05）. Compared with the control group,E2 levels,FSH levels and improved Kupperman scores in the standard dose group changed more significantly（all P<0.05）. E2 and FSH levels in the low dose group changed less than that in the standard dose group（all P<0.05）,while improved Kupperman scores was close to that in the standard dose group. The incidence rate of side effects in the low dose group was 2.50%,which was lower than 20.00% in the standard dose group（P<0.05）. @*Conclusion@#For young patients with cervical squamous cell carcinoma,using low dose HRT may less affects E2 and FSH levels than using the standard dose,but could achieve similar effects in treatment of menopausal-related symptoms.

Expression of RET gene in cervical squamous cell carcinoma / 实用医学杂志

Objective To explore the expression of RET in cervical squamous carcinoma tissues and evaluate its relationship with cervical squamous carcinoma clinical pathological indexes and its prognostic value. Methods The expression and distribution of RET in normal cervical tissues ,CINⅠ,CINⅡ& CINⅢ and cervical squamous carcinomas tissues were detected by immunohistochemistry in wax blocks. Clinical data and follow-up data are integrated to analyze its relationship with clinical pathological factors and prognosis value. Results The positive rate of RET protein in cervical squamous carcinomas tissues is higher than in other tissues.The positive rate was related to FIGO stage and lymph node metastasis(P0.05). The result of survival analysis with Kaplan-Meier method showed poorer disease-free survival time in the patients with high expression of RET (P < 0.05). Prognostic analysis of patients with cervical cancer through COX proportional hazard regression model suggested that RET expression was an independent prognostic factor. Conclusions RET has been involved in the progression ,FIGO stage and metastasis of cervical squamous cell carcinomas.

Expression of Merlin protein in female cervical cancer of Han ,Tibetan and Hui nationalities in Qinghai / 实用医学杂志

Objective To explore the expression of the Merlin protein in normal cervix and cervical can-cer of the Han,Tibetan and Hui nationalities in Qinghai. Methods Immunohisto-chemical staining was per-formed to detect the expression of Merlin in 108 cases of cervical carcinoma(40 cases of Han,38 cases of Tibetan and 30 cases of Hui nationality)and 107 cases of normal cervix(40 cases of Han,37 cases of Tibetan and 30 cas-es of Hui nationality). Results The positive expression rates of Merlin in normal cervix were 90.0%,91.9%and 86.7%respectively and those in cervical carcinoma were 17.5%,18.4%and 16.7%respectively. There was signifi-cantly statistical difference(P0.05). The expression of Merlin was not correlated with age,FIGO stage,lymph metastasis and cell differentiation(P > 0.05)in cervical carcinoma of three ethnic groups. Conclusion The decrease or even deletion of Merlin may be involved in the development of cervical can-cer,and it plays an important role in cervical cancer. The expression of Merlin exerts no effect on the occurrence of cervical cancer and it is not associated with the clinical characteristics of the patients ,suggesting that it may not be involved in the invasion and metastasis of cervical cancer.

Expression and clinical pathological significance of CD138 in cervical lesion tissues / 中国免疫学杂志

Objective: To study the expression of CD138 in normal cervical mucosal tissue,cervical intraepithelial neoplasia ( CINⅠ/Ⅱ and CINⅢ) and cervical squamous cell carcinoma.And to investigate the clinical pathologic significance of CD 138 expression with lymph node metastasis , microvascular density ( MVD ) , CD68 expression and clinical stage in cervical squamous cell carcinoma.Methods:To detected the expression of CD 138 in 120 cases of cervical squamous cell carcinoma ,106 cases of CINⅢ,14 cases of CINⅠ/Ⅱand 54 cases of normal cervical mucosa tissues.Results: The expression of CD138 was lowest in cervical cancer tissue,followed by normal cervical mucosal tissue ,CIN I/II and CINIII,that there had significant difference (P<0.001).The expression level of CD138 was higher in without lymph node metastasis group than in lymph node metastasis group ( P<0.05 ).In cervical cancer , the expression level of CD 138 was higher in early stage ( stage 0 andⅠ) than in advanced stage (Ⅱ) ( P<0.001 );and higher in CD68 expression negative group than in positive group (P<0.05).Furthermore,MVD was higher in CD138 expression negative group than in positive group ( P<0.05 ).Conclusion: CD138 play an important role in the process of development of cervical squamous cell carcinoma,especially for the role of lymph node metastasis is more obvious.CD138 could be used as a indicators for determinate the process of progress in cervical squamous cell carcinoma.

Pre-treatment circulating regulatory T cell count analysis of advanced cervical squamous cell ;carcinoma patients / 中国癌症杂志

Background and purpose:Due to the lack of cost-effective pre-treatment predictors for advanced cervical squamous cell carcinomas treated with concurrent chemoradiotherapy (CCRT), both baseline circulating CD4+CD25+CD127Low/- regulatory T cell (Treg) count and serum squamous cell carcinoma antigen (SCC-Ag) level were measured for this feasibility study. Methods: Peripheral blood samples were collected from 44 patients with stageⅡB-ⅣA cervical squamous carcinomas before CCRT. Flow cytometry immunophenotyping and enzyme-linked immunosorbent assay were used for circulating CD4+CD25+CD127Low/-Treg count and serum SCC-Ag level testing,respectively. Clinical and pathological characteristics were retrospectively reviewed to analyze the predictive value of the 2 indexes. Results:The baseline circulating CD4+CD25+CD127Low/-Treg count was lower in the patient group with positive treatment response than in the group with negative response [(8.78±2.80)%vs (10.95±2.56)%, P<0.05], and the serum SCC-Ag level showed no signiifcant difference between the 2 groups. No correlation was detected between these 2 markers (Spearman’rho=-0.093, P=0.540). Determined by plotting receiver operating characteristic curves, the best cut-off points were 9.76%for circulating CD4+CD25+CD127Low/-Treg count and 9.50 ng/mL for serum SCC-Ag level, respectively. Univariate analysis showed that pretherapeutic circulating CD4+CD25+CD127Low/-Treg count (OR=1.901, 95%CI:1.112-3.219, P=0.017), but not serum SCC-Ag level (OR=0.998, 95%CI:0.001-4.253, P=0.897), was predictive of clinical response to CCRT. Multivariate Logistic regression analysis revealed that pre-treatment CD4+CD25+CD127Low/-Treg count was an independent predictor for clinical response to CCRT (OR=3.115, 95%CI:1.253-7.742, P=0.014). Conclusion:Pretherapeutic circulating CD4+CD25+CD127Low/-Treg count is a feasible method to predict clinical response to CCRT in patients with advanced cervical squamous cell carcinomas.

Relationship between the expressions of PI3K and regional angiogenesis,invasion,metastasis,and prognosis in cervical squamous cell carcinoma / 国际检验医学杂志

Objective The expressions of PI3K in invasive squamous cell carcinoma of cervix and their clinical significance were investigated .Methods The expressions of PI3K ,Ki‐67 and CD34 protein in 28 cases of normal cervical epithelium (NCE) ,36 cases of cervical intraepithelial neoplasm (CIN) and 68 cases of squamous cell carcinoma of cervix (SCC) were detected by immunohisto‐chemistry SP method .Results The positive expression rates of PI3K in NCE ,CIN and SCC were 25 .00% ,55 .56% and 85 .29% , respectively .The positive expression rates of PI3K increased remarkably from NCE and CIN to SCC(P0 .05) .In the cases with FIGO staging Ⅱ ,poorly differentiated tissue and pelvic lymph node metasta‐sis ,The positive expression rate of PI3K significantly higher than those in the cases without them(P<0 .05) .Conclusion The o‐ver‐expression of PI3K may lead to up regulation of tumor angiogenesis and cancer cell proliferation in SCC ,and may promote tumor Metastasis and progress of SCC .

No postoperative survival benefit in concurrent chemoradiation treated patients with low-risk early-stage cervical squamous cell carcinoma / 中国肿瘤临床

Objective:The benefits of postoperative adjuvant therapy method for low-risk early-stage cervical squamous cell carcinoma were investigated. Methods:A total of 133 patients with low-risk early-stage cervical squamous cell carcinoma were treated at Shandong Cancer Hospital&Institute from February 2008 to March 2012. All patients received adjuvant therapy:42 were treated with pelvic ra-diotherapy (RT), 47 were treated with adjuvant chemotherapy (CT)+intracavitary radiotherapy (ICRT), and 44 were treated with concurrent chemoradiation (CCRT). Disease-free survival (DFS) and complications of the therapy were evaluated. Results:No significant differences in DFS were observed in the patients treated with RT, CT+ICRT, and CCRT (P>0.05), and the three-year DFS rates were 94.0%, 93.4%, and 97.6%, respectively. The frequencies of grade III to IV acute toxicities were significantly higher in patients treated with CCRT (34.1%) than in those treated with RT (9.5%) or CT+ICRT (16.7%) (P0.05). Grade I to II late toxicity was significantly more frequent in the CCRT (25%) and RT (19.0%) groups compared with the CT+ICRT group (4.3%) (P>0.05), but no statistically significant differences were observed between the CCRT and the RT groups (P>0.05). Conclusion:CT+ICRT or RT has a three-year DFS rate equivalent to CCRT but with fewer therapy com-plications for low-risk early-stage cervical squamous cell carcinoma.

Correlation of lymphatic vessel density with a high mobility group Box-1 protein and tumor-associated macrophages in cervical carci-noma / 中国肿瘤临床

Objective: To detect the correlation of lymphatic vessel density (LVD) with a high mobility group box-1 Protein (HMGB1) and tumor-associated macrophages (TAMs) in cervical carcinoma and the effect on prognosis. Methods:Immunohistochem-istry was applied to detect HMGB1, CD68, and D2-40 expressions in cervical squamous cell carcinoma in 93 cases. t test,χ2 test, Spear-man rank correlation analysis, Kaplan-Meier method, and Cox regression were performed to analyze the expression levels, correlation, and prognosis. Results: HMGB1 protein, CD68, and D2-40 were highly expressed in CSCC. As HMGB1 and TAM expressions in-creased, lymphatic vessel density increased. As HMGB1 and TAM expressions decreased, lymphatic vessel density decreased. Positive correlations were also found between the HMGB1 protein, TAM content, and LVD. In the group with low HMGB1 and TAM expres-sions, the survival time of the group with a high LVD expression was significantly lower than that of the group with a low LVD expres-sion. A multivariate Cox regression model showed that HMGB1 and lymph node metastasis were independent prognostic factors. TAMs and LVD were not independent prognostic factors. Conclusion:HMGB1 proteins and TAMs were highly expressed in CSCC. Patients who exhibit increased HMGB1 expression or increased TAM count consequently show enhanced LVD expressions, increased lymph node metastasis, and poor prognosis.

Investigation of microRNA expression on Uygur cervical squamous cell carcinoma in southern Xinjiang / 中国癌症杂志

Background and purpose:Cervical cancer is one of the most common cancer in Xinjiang, especially for Uygur from southern Xinjiang and its pathogenesis is not clear. MicroRNA (miRNA) is a class of small non-coding RNA playing an important regulatory role. Its expression and dysfunction is closely related to the development of tumors. In this study, we screen and preliminary analyse expression of miRNA in cervical squamous cell carcinoma samples with human papillomavirus (HPV) 16 positive of Uygur patients. The target genes of miRNA were predicted.Methods:miRNAs were pre-screened by using miRNA microarray technology in 5 cases of HPV16 positivity Uygur patients from southern Xinjiang with cervical squamous cell carcinoma. Fifteen cases specimens were examined by qRT-PCR for preliminary veriifcation, and 83 cases of cervical cancer were detected and analysed the expression of miRNA; Targeted genes were predicted by using four softwares of target scan, miRwalk, miRanda and Pictar.Results:Eighteen differentially expressed miRNAs were selected by SAM software in 5 cases of HPV16 positivity southern Xinjiang Uygur cases with cervical squamous cell carcinoma.miRNA-138 and miRNA-720 were found expressed signiifcantly different by initial veriifcation. Contrasted with 40 normal cases, miR-138 and miR-720 were down-regulated in 83 Uygur patients from southern Xinjiang with cervical squamous cell carcinoma (P0.05). miRNA-720 was correlated with clinical stage and tumor size (P<0.05); And the commonly targeted gene between miRNA-138 and miRNA-720 was EZH2.Conclusion:miRNA-138 and miRNA-720 were downregulated in Uygur patients from southern Xinjiang with cervical squamous cell carcinoma, and the common target gene was EZH2.The expression of miR-720 and miR-138 were correlated with relevant risk factors of invasion and metastasis.

Study on the expression of PINCH and vascular endothelial growth factor C in cervical squamous cell carcinoma / 中国综合临床

Objective To study the expression of PINCH and vascular endothelial growth factor C (VEGF-C) in cervical squamous cell carcinoma.Methods We detected the expression of PINCH and VEGF-C by immunohistochemistry SP in 58 cervical squamous cell carcinoma cases and 30 normal cervical epithelial tissue and analyzed their relationship to the clinical pathological features.Results The expression of PINCH and VEGF-C in 58 cervical squamous cell carcinoma(62.1％,36/58 ;67.2％,39/58 ) were higher than that in normal cervical epithelial tissue(0,0/30).The difference was significant( x2 =31.512,12.534,P ＜ 0.001 ).The expression of PINCH protein was not significantly associated with the age,tumor size and tumor differentiation grade ( P ＞ 0.05 ),but was associated with the lymph node metastasis and clinical stage ( x2 =9.090,8.236,P ＜ 0.001 ).The expression of VEGF-C had no significant correlationship with the age and tumor size( P ＞ 0.05 ) but had a correlationship with the lymph node metastasis,tumor differentiation grade and clinical stage( x2 =10.775,13.496,5.001,P ＜ 0.05 ).The expression of VEGF-C was correlated with the expression of PINCH protein( C =0.341,P ＜ 0.01 ).Conclusion It is possible that VEGF-C and PINCH take part in the development and progress of cervical squamous cell carcinoma and play an important role in the invasion and metastasis mechanism altogether.

Promoter hypermethylation and loss of heterozygosity of FHIT genes in squamous cell carcinoma of uterine cervix / 부인종양

OBJECTIVE: This study was to investigate the status of hypermethylation and loss of heterozygosity (LOH) in chromosome 3p tumor-suppressor gene for cervical carcinoma. METHODS: We examined the promoter methylation status of the chromosome 3p gene, fragile histidine triad (FHIT), in 37 samples of cervical squamous cell carcinoma and corresponding noncancerous tissues using a methylation-specific polymerase chain reaction. We also analyzed the 37 paired samples for LOH at two loci on chromosome 3p. RESULTS: Promoter hypermethylation in FHIT was detected in 24% of tumors, whereas no hypermethylation was detected in the corresponding noncancerous tissues. LOH in the regions of FHIT was observed in 10% of informative cases. There were no correlations between LOH and promoter hypermethylation for the gene. FHIT hypermethylation was associated with small tumors and, when adjusted for tumor size, correlated significantly with more frequent lymph node metastasis. CONCLUSION: Promoter hypermethylation and LOH of FHIT gene may play a role in cervical carcinogenesis. In addition, hypermethylation of FHIT may be associated with the status (aggressiveness) of cervical carcinoma.