Association Between the CDC6 G1321A Polymorphism and the Risk of Cervical Cancer

2010 ◽  
Vol 20 (5) ◽  
pp. 856-861 ◽  
Author(s):  
Xing-Dong Xiong ◽  
Li-Qin Zeng ◽  
Qing-Yuan Xiong ◽  
Sheng-Xiang Lu ◽  
Zhi-Zhen Zhang ◽  
...  

Introduction:Cell division cycle protein 6 (CDC6) plays critical roles in DNA replication and carcinogenesis. The biological significance of the CDC6 G1321A polymorphism (V441I, rs13706) on cervical carcinogenesis is still unknown. Here, we examined the potential influence of this polymorphism on cell proliferation and the individual's susceptibility to cervical cancer.Methods:We genotyped the CDC6 G1321A polymorphism in 87 cervical cancer cases and 110 healthy female subjects. Unconditional logistic regression analysis was used to estimate the association between the genotypes and the risk of cervical cancer. The BrdU incorporation assay was applied to analyze the effect of this polymorphism on cell proliferation.Results:Compared with the GG homozygotes, the cervical cancer risk was significantly reduced in the individuals with the heterozygous AG genotype (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.28-0.98; P = 0.042) or the homozygous AA genotype (OR, 0.29; 95% CI, 0.09-0.89; P = 0.030). Further stratified analyses showed that the decreased risk of cervical cancer was more evident among younger subjects (≤44 years old) with the AG or AA genotypes (OR, 0.44; 95% CI, 0.21-0.92; P = 0.029 and OR, 0.12; 95% CI, 0.03-0.61; P = 0.010, respectively). The BrdU incorporation assay showed that 293T cells transfected with CDC6-441I (1321A) had a lower proliferation rate in comparison with those transfected with CDC6-441V (1321G), although the difference did not reach statistical significance at the 0.05 level.Conclusions:The CDC6 G1321A polymorphism may contribute to the risk of cervical cancer. Further studies with more subjects and in diverse ethnic populations are necessary to confirm the general validity of our findings.

2019 ◽  
Vol 20 (3) ◽  
pp. 545 ◽  
Author(s):  
Sergio Córdova-Rivas ◽  
Ixamail Fraire-Soto ◽  
Andrea Mercado-Casas Torres ◽  
Luis Servín-González ◽  
Angelica Granados-López ◽  
...  

The micro RNA (miR)-34 family is composed of 5p and 3p strands of miR-34a, miR-34b, and miR-34c. The 5p strand’s expression and function is studied in cervical cancer. The 3p strand’s function and regulation remain to be elucidated. To study the function of the passenger strands of miR-34 family members, we overexpressed 5p and 3p strands using a synthetic miRNA in cervical cell lines. Cell proliferation was evaluated using crystal violet. Migration and invasion were tested using transwell assays, Western blot, and zymography. Possible specific targets and cell signaling were investigated for each strand. We found that miR-34a-5p inhibited proliferation, migration, and cell invasion accompanied by matrix metalloproteinase 9 (MMP9) activity and microtubule-associated protein 2 (MAP2) protein reduction. We also found that miR-34b-5p and miR-34c-5p inhibit proliferation and migration, but not invasion. In contrast, miR-34c-5p inhibits MMP9 activity and MAP2 protein, while miR-34b-5p has no effect on these genes. Furthermore, miR-34a-3p and miR-34b-3p inhibit proliferation and migration, but not invasion, despite the later reducing MMP2 activity, while miR-34c-3p inhibit proliferation, migration, and cell invasion accompanied by MMP9 activity and MAP2 protein inhibition. The difference in cellular processes, MMP2 and MMP9 activity, and MAP2 protein inhibition by miR-34 family members suggests the participation of other regulated genes. This study provides insights into the roles of passenger strands (strand*) of the miR-34 family in cervical cancer.


Author(s):  
Jennifer Davies ◽  
Alice Spencer ◽  
Sian Macdonald ◽  
Lucy Dobson ◽  
Emily Haydock ◽  
...  

Objective: To review the effect of the COVID-19 pandemic on the presentation of Cervical cancer. Design/ Setting: Retrospective study involving the Regional Cancer Centres in the M62 Group. Methods: Data was collected for two equal time periods. All cervical cancers were included and FIGO 2018 staging was used for the data collection. P values were calculated using binomial hypothesis test for the difference in staging. Time from symptoms to diagnosis was assessed using a normal distribution test. All other calculations were performed using chi-squared test. Statistical significance was considered if p values were <0.05. Main outcome measures: Histology, stage at diagnosis, date of onset of symptoms, investigation and type of treatment. Results: A total of 406 cases of cervical cancer were reviewed; 233 from May – October 2019 (pre-COVID) and 173 between May – October 2020 (post COVID); representing a significant reduction in new cervical cancer diagnoses of 25% post COVID (p<0.001) There was a 42% increase in the delay from start of symptoms to diagnosis Post COVID. Pre COVID, 27% of patients presented with Stage 3 or 4 disease, whilst during COVID this was 38%; statistically significant (p <0.001). When we evaluated the treatments received between the two time periods, this was also statistically significant (chi-squared, p=0.0005). Conclusions: This study has demonstrated a statistically significant increase in the stage of cervical cancer at diagnosis and a change in treatment for cervical cancer following the onset of COVID-19. The implications of this are discussed.


2019 ◽  
Vol 400 (8) ◽  
pp. 1069-1078 ◽  
Author(s):  
Anjun Zuo ◽  
Peng Zhao ◽  
Yu Zheng ◽  
Hui Hua ◽  
Xingang Wang

Abstract Breast cancer is the most commonly diagnosed cancer in women worldwide. Tripterine is an important active component isolated from Triperygium wilfordii Hook F. This study investigated the effects of tripterine on breast cancer cell proliferation, migration, invasion and apoptosis, as well as microRNA-15a (miR-15a) expression. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure the expression of miR-15a. Cell transfection was conducted to change the expression of miR-15a. Viability, proliferation, migration, invasion and apoptosis of MDA-MB-231 cells were assessed using the cell counting kit-8 (CCK-8) assay, BrdU incorporation assay, Annexin V-FITC/PI apoptosis detection kit and two-chamber Transwell assay, respectively. Expression of key factors involving in cell proliferation, migration, invasion and apoptosis, as well as the PI3K/AKT and JNK pathways, were evaluated using Western blotting. We found that tripterine inhibited MDA-MB-231 cell viability, proliferation, migration and invasion, but induced cell apoptosis. Moreover, tripterine up-regulated the expression of miR-15a in a concentration-dependent manner and miR-15a participated in the effects of tripterine on MDA-MB-231 cell proliferation, migration, invasion and apoptosis. In addition, tripterine inactivated PI3K/AKT and JNK pathways in MDA-MB-231 cells by up-regulating miR-15a. In conclusion, tripterine inhibited proliferation, migration and invasion of breast cancer MDA-MB-231 cells by up-regulating miR-15a and inactivating PI3K/AKT and JNK pathways.


2010 ◽  
Vol 20 (6) ◽  
pp. 1087-1091 ◽  
Author(s):  
Rajiv Samant ◽  
Sofya Kobeleva ◽  
Choan E ◽  
Khalid Balaraj ◽  
Tien Le ◽  
...  

Purpose:Radiotherapy with concurrent cisplatinum-based chemotherapy became a standard recommendation for the management of advanced cervical cancer in 1999. We reviewed our experience with this approach to determine the impact on patient outcomes.Methods:A retrospective review of all cervical cancer patients treated with curative intent using radical radiotherapy ± chemotherapy from 1992 to 2005 was performed. Survival and relapse rates were analyzed using the Kaplan-Meier method and were compared using the log-rank test.Results:During this period, 224 treated patients were identified: 153 (68%) were treated between 1992 and 1999 (group 1) and 71 (32%) were treated after 1999 (group 2). The median age was 53 and 55 years with a median follow-up of 49 and 34 months for groups 1 and 2, respectively. Stage classification and histological diagnosis were similar for both groups. Treatment usually consisted of external beam pelvic radiotherapy (40-45 Gy in 20-25 fractions) followed by low-dose rate brachytherapy (35-40 Gy to point A). Chemotherapy consisted of weekly intravenous cisplatinum (40 mg/m2) given concurrently with pelvic radiation. The proportion of patients receiving chemotherapy increased significantly after 1999, 12% in group 1 compared with 79% in group 2 (P < 0.01). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 53% and 54% for group 1 and 64% and 67% for group 2. The improvement in PFS for group 2 approached statistical significance (P = 0.06), but the difference in OS did not.Conclusions:There has been a significant increase in the use of concurrent chemoradiation for cervical cancer treatment after 1999, and this seems to have led to higher rates of PFS and OS, although these have yet to achieve statistical significance.


2020 ◽  
Author(s):  
Kang Zhu ◽  
He Bai ◽  
Mingzhu Mu ◽  
Yuanyuan Xue ◽  
Zhao Duan

Abstract Background Given its crucial role in human malignancies, how Ring finger protein 6 (RNF6) functions in cervical cancer has yet to be elucidated. In our research, we explored the biological significance of RNF6 in cervical cancer HeLa cells and its possible regulatory mechanism. Methods The expression levels of RNF6 mRNA and protein in cervical cancer tissues and cells were both analyzed, the former by Gene Expression Profiling Interactive Analysis (GEPIA), and the latter by quantitative real-time PCR (qRT-PCR) and immunohistochemistry assays. In vitro cell proliferation was tested through MTT assay and flow cytometer was used to detected Cell apoptosis. The activation of ERK(extracellular signal regulated kinase) was explored by Western Blot. Results In the present research, we found that the expression of RNF6 was high in both primary tissues and cervical cancer cells. RNF6 could promote cervical cancer HeLa cells growth. Once knockdown of RNF6 in cervical cancer cells, cell proliferation could be suppressed and cell apoptosis was promoted. Moreover, its elevation had an adverse effect on the prognosis of cervical cancer. Further studies showed that ERK activation is one of the potential mechanisms. Conclusion These findings provided evidence that the up-regulated RNF6 could activate the MAPK/ERK pathway to regulate the cell growth in cervical cancer, which suggested that RNF6 could be a promising target for diagnosis and treatment for cervical cancer.


2005 ◽  
Vol 64 (8) ◽  
pp. 1823-1832 ◽  
Author(s):  
M. Moussa ◽  
C. Perreau ◽  
G. Baril ◽  
G. Duchamp ◽  
M. Vidament ◽  
...  

2020 ◽  
Vol 19 (3) ◽  
pp. 49-64
Author(s):  
E. M. Bogdanova ◽  
Yu. L. Trubacheva ◽  
O. M. Yugai ◽  
S. V. Chernyshov ◽  
E. G. Rybakov ◽  
...  

AIM: to compare multiparametric endorectal ultrasound (ERUS) and enhanced imaging colonoscopy in the diagnosis of early colorectal cancer.PATIENTS AND METHODS: the study included 78 patients with epithelial rectal tumor. All the patients underwent multiparametric ERUS and colonoscopy with examination by narrow beam imaging (NBI) at optical magnification. All the patients were operated.RESULTS: a morphological examination removed specimens revealed adenomas in 48 cases, in 19 specimens – adenocarcinomas in situ and T1, and in 11 specimens – adenocarcinomas with invasion of the muscle layer or deeper. When calculating the accuracy indicators of diagnostic methods for groups of patients with adenoma, Tis-T1 adenocarcinoma, and T2-T3 adenocarcinoma, the difference in the sensitivity and specificity of the methods in none of the presented groups did not reach the level of statistical significance (p>0.05).ROC analysis showed that ultrasound has a prognostic value comparable to colonoscopy. The area difference was 0.013 (p=0.85).CONCLUSION: endoscopy and ultrasound have similar value in the diagnosis of malignant transformation of rectal adenomas.


1972 ◽  
Vol 69 (1) ◽  
pp. 165-173 ◽  
Author(s):  
H. Schmidt ◽  
I. Noack ◽  
K. D. Voigt

ABSTRACT The effect of testosterone and 5α-dihydrotestosterone on protein and nucleic acid content as well as on the activities of some enzymes has been studied in the ventral prostate and the seminal vesicles of immature castrated rats. Both androgens were given intraperitoneally in doses of 1 mg daily for one or three days the rats were sacrificed one day after the last injection. In the prostate it was found that 5α-dihydrotestosterone had a greater effect on DNA increase, i. e. cell proliferation than testosterone, whereas cell metabolism was stimulated by the two androgens to nearly the same extent. In the seminal vesicles a single dose led to the same results as had been obtained in the prostate, i. e. a greater cell proliferative action of 5α-dihydrotestosterone and an equal stimulation of cell metabolism by testosterone and 5α-dihydrotestosterone was also observed. When three doses of the two androgens were given, cell proliferation as well as cell metabolism in the seminal vesicles were significantly more increased after 5α-dihydrotestosterone than after testosterone. The difference of action after systemic administration of the two androgens is explained by their different accumulation and by their different peripheral metabolism in the target tissues. From the partly independent effects of various androgens on cell proliferation and cell metabolism the conclusion may be drawn that there exist at least two intracellular sites of action.


2019 ◽  
Vol 17 (5) ◽  
pp. 265-275
Author(s):  
Y. Peristiowati ◽  
Y. Puspitasari ◽  
Indasah

This study is aimed at analyzing the anticancer properties of papaya leaf extract, specifically the inhibition of cell proliferation and apoptotic induction through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p53 pathways. Twenty-five mice (Mus musculus), aged 2 months and weighing 20–30 g, was injected with 0.5 mg dexamethasone for 7 days. The mice were then injected intracutaneously with 1 ml of HeLa cells (8 × 106 HeLa cells/microliter). The mice were divided into five groups (5 each): negative control (P1) (5% CMC-Na, sodium carboxymethyl cellulose), treatment II (225 mg/kg BW (body weight) papaya leaves methanol extract), treatment III (450 mg/kg BW), treatment IV (750 mg/kg BW), and treatment PV (2 mg alcohol anticancer drug). Papaya leaf extract treatments were applied for 2 weeks. Then, the tumor tissue was isolated for hematoxylin and eosin staining. Immunohistochemical imaging was used to detect Ki-67, caspase-3, NF-κB, and p53 expression. Further analysis was undertaken using the ImmunoRatio software program. The results indicated that administration of papaya leaf methanol extract significantly increased the expression of NF-κB and p53 at a dose of 450 mg/kg BW. Our results also showed that the mice treated with 450 mg of papaya leaf extract per kg of BW (P3) had the largest increase of caspase-3 expression compared to the negative control group. Papaya leaf ethanol extract decreased the cancer cell proliferation index and increased apoptosis of cancer cells in animal models of cervical cancer; it may also work to increase NF-kB expression and expression of the p53 gene.


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