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Telomere length is associated with cancer as well as aging. Telomerase reverse transcriptase (TERT), telomere RNA component (TERC) and oligonucleotide/oligosaccharide-binding fold containing 1 (OBFC1) are known to be involved in telomere length regulation. selleck chemicals llc The tumor suppressor p53 (TP53), which has been shown to interact with tumor protein p53-binding protein 1 (TP53BP1), is implicated in the response to telomere shortening and aging. Polymorphisms in the TP53 and TP53BP1 genes are associated with various types of cancer. The aim of this study is to evaluate the impact of aging-related polymorphisms on lung cancer risk.
This case-control study consists of 462 lung cancer cases and 379 controls from Japan. We examined the effect of TERT rs2736100, TERC rs1881984, OBFC1 rs11191865, TP53 rs1042522 and TP53BP1 rs560191 on the risk of lung cancer using a Taq-Man real-time PCR assay. Unconditional logistic regression was used to assess the adjusted odds ratios (ORs) and 95% confidence intervals (CIs).
None of the main effects of any of the telomere-related polymorphisms were related to the risk of lung cancer. Similarly, none of the interactive effects of any of the telomere-related polymorphisms with smoking were associated with lung cancer risk. The significant multiplicative interaction between TERT rs2736100 and TP53BP1 rs560191 was statistically significant (OR for interaction = 0.34, 95% CI = 0.14-0.84). The multiplicative interaction between OBFC1 rs11191865 and TP53BP1 rs560191 was also statistically significant (OR for interaction = 2.44, 95% CI = 1.02-5.87) but the OR for interaction was in the opposite direction.
Our findings indicate that TP53BP1 rs560191 may predispose to lung cancer risk depending on the genotypes of telomere-related polymorphisms. Additional studies are warranted to confirm the findings suggested in the present study.<br />.
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one of the female-specific diseases with a high incidence and mortality is cervical cancer. The main cause of cervical cancer is infection with Human papilloma virus (HPV). Low-grade squamous intraepithelial lesions (LSIL) and High-grade squamous intraepithelial lesions (HSIL) usually is caused by an HPV infection. Considering the role of microRNAs (miRNAs) as diagnostic biomarkers for a variety of cancers, the aim of this study was to determine miR-92a-5p and miR-155-5p expression levels in LSIL and HSIL Pap Smear samples.
After initial bioinformatic studies, A total of 75 samples (25 samples of patients with LSIL, 25 patients with HSIL and 25 healthy individuals) were subjected to RNA extraction and cDNA synthesis. The expressions levels of confirmed miRNAs in samples of patients with LSIL, HSIL and healthy individuals were evaluated by Real time PCR analysis. To demonstration the role of predicted miRNAs as novel biomarkers in diagnosis of LSIL and HSIL, ROC curve analysis was done.
Bioinformatics results showed that miR-92a-5p and miR-155-5p target the HPV E6 and E7 genes. The expression levels of these miRNAs were strikingly higher in Pap smear of patients with LSIL than in the healthy individuals (35.36, P = 0.001) (62.23, P = 0.001). Similarity, expression levels of miR-92a-5p and miR-155-5p were amazingly higher in patients with HSIL than in the healthy individuals (33.62, P= 0.001) (69.07, P= 0.001). Although, the levels of miR-92a-5p (0.95, P = 0. 85) and miR-155-5p (1.11, P = 0.84) exhibited no statistical differences between patients with LSIL and HSIL. Also, ROC curve analyses verified that miR-92a-5p and miR-155-5p are specific and sensitive and may serve as new biomarkers for the early detection of cervical cancer.
These data suggest miR-92a-5p and miR-155-5p, which are upregulated in LSIL and HSIL, can be consider as predictive biomarkers for the prognosis of cervical cancer patients.<br />.
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To indicate the effect of Epigallocatechin gallate (EGCG) and Cisplatin (DDP) on proliferation of gastric cancer BGC-823 cells and the relative underlying mechanism.
Cultured BGC-823 cells were treated by 5 μg/mL DDP, 25 μg/mL EGCG and combined 5 μg/mL DDP with 25 μg/mL EGCG, a blank group was used as control. Cell morphology was observed by 4',6-diamidino-2-phenylindole (DAPI) staining. The ability of cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay. The cell cloning rate was determined by colony formation assay. The ability of cell migration was detected by cell scratch test. The cell cycle distributions and apoptosis were analyzed by flow cytometry, The expression of p19Arf, p53, p21Cip1 mRNA was determined by RT-qPCR. The protein levels of p19Arf, p53, p21Cip1 were measured by Western blot.
Compared with DDP or EGCG treatment alone, EGCG combined with DDP treatment significantly caused nuclear shrinkage, reduced the proliferation rate, the ability of cell clone and migration. EGCG combined with DDP treatment caused cell cycle arrest in G1 phase in BGC-823 cells, increase of apoptosis (21.3%) vs EGCG (7.25%) and DDP (3.86%) single-use group (p <0.01), up-regulated gene and protein expressions of p19Arf, p53, p21Cip1 (p <0.01).
EGCG can enhance the effect of DDP on inhibiting BGC-823 cell proliferation and inducing apoptosis via activating the p19Arf-p53-p21Cip1 signaling pathway.
EGCG can enhance the effect of DDP on inhibiting BGC-823 cell proliferation and inducing apoptosis via activating the p19Arf-p53-p21Cip1 signaling pathway.
The aim of this study was to assess quality of life (QoL) in patients with unresectable hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) compared to TACE plus radiofrequency ablation (RFA) done at the same sitting, and to assess tumor therapy response after these 2 palliative interventions.
73 patients with unresectable HCC (BCLC-B) were included. Patients with tumor ≤ 5 cm were subjected to TACE (N = 45) while patients with tumors > 5 cm were subjected to TACE followed immediately by RFA (N = 28). QoL was evaluated with two validated questionnaires (EORTC QLQ-30 and EORTC HCC18). These questionnaires were filled out before intervention, 2 weeks and 2 months after intervention. Pre/post interventional changes were analyzed. The modified response evaluation criteria in solid tumor (mRECIST) were employed for the evaluation of therapeutic efficacy.
Baseline global health status/QoL was significantly higher in TACE group (64.1%) compared to TACE-RFA group (51.2%). Two weeks after intervention the absolute decrease in global health state was higher in TACE-RFA (- 12.