233 research outputs found
Chromatin modifications of hTERT gene in hTERT-immortalized human mesenchymal stem cells upon exposure to radiation
No full textRegulation of telomerase activity is thought to participate in the cellular response to ionizing radiation. Epigenetic mechanisms play a role in this regulation, as well as other mechanisms such as transcription, phosphorylation, etc. Here, we investigated chromatin modifications in telomerase promoter upon exposure to ionizing radiation in human mesenchymal stem cells (hMSC) and telomerase-immortalized hMSCs (hMSC-telo1) together with a hMSC-telo1 cell line in which TRF2 expression was partially repressed (siTRF2 hMSC-telo1). Histone methylations and acetylations were compared in all cell lines after exposure to various doses of ionizing radiation (0.1, 1, 2.5 and 15 Gy) using chromatin immunoprecipitation assay. hTERT gene was shown to be quickly regulated through H3, H4 acetylations, as well as with H3K4 and H3K9 methylations, following radiation exposure, although the kinetic of hMSC-telo1 cells were different, indicative of the higher radioresistivity of these cells. To the author's surprise, there was an upregulation of endogenous telomerase activity in the hMSC-telo1 cells, even though the cells had already expressed high levels of ectopic hTERT. Our results show that telomerase regulation is one of the primary actions in response to damage and epigenetic factors play a major role in this regulation. Our results also suggested that partial silencing of TRF2 enhances the radiosensitivity of these cells, and endogenous telomerase is upregulated upon radiation, even under ectopic expression of hTERT in these cells
Morphological alterations and distribution of occludin in rat testes after bilateral vasectomy
No full textThe aim of study was to investigate the fate and the morphology of the cells which constitute the spermatogenic line, and to determine the distribution of occludin in the testis in adult vasectomized Wistar rats. The rats were divided into two groups: control group (sham-operated) and vasectomized group. One, 3 and 6 months after sham and vasectomy operations, testis samples were examined. The weight of the testes was found to be reduced 3 and 6 months after vasectomy. There was vacuolization in the seminiferous tubules one month after vasectomy. The tubules showed severe atrophy 3 and 6 months after vasectomy. The occludin immunolabeling in the 3- and 6-month groups was weak and diffuse, and the density of the protein was found to be decreased. The increase in the number of apoptotic cells was accompanied by a time-dependent decrease in the number of haploid, diploid and tetraploid cells. This study demonstrated that vasectomy causes degeneration in the seminiferous tubules with alterations in occludin distribution with a decrease in the number of spermatogenic cells. Moreover, these alterations increase in a time-dependent manner. (C) 2011 Elsevier GmbH. All rights reserved
Role of TRF2 and TPP1 regulation in idiopathic recurrent pregnancy loss
No full textTelomeres are the tandem repeats (TTAGGG) present at the ends of the chromosomes that ensure chromosome stability and protect chromosomes from degradation. Telomeres in somatic human cells shorten after every cellular division and are linked to the cellular senescence. In this study we have investigated telomere length and expression of shelterin genes in aborted fetus material from idiopathic recurrent pregnancy losses. Telomere length was measured using Telomere Restriction Fragment Length (TRF) analysis. The gene expression levels for important shelterin complex proteins (TRF1, TRF2, POT1, and TPP1) were determined by Real-time Quantitative Reverse Transcriptase PCR (qRT-PCR). Our results demonstrated down regulation of TRF2 and TPP1 and a strong decline in average telomere length in abort material from women suffering from idiopathic recurrent pregnancy loss. We suggest that shorter telomere length and downregulation of the major shelterin components TRF2 and TPP1 leading to telomere uncapping, might play a critical role in recurrent pregnancy loss. (C) 2019 Elsevier B.V. All rights reserved
Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients
No full textBackground: Telomeres are protective caps consisted of specific tandem repeats (5 '-TTAGGG-3 '). Shortening of telomeres at each cell division is known as mitotic clock of the cells, which renders telomeres as important regulators of lifespan. TRF2 is one of the critical members of shelterin complex, which is a protein complex responsible from the preservation of cap structure, and loss or mutation of TRF2 results in DNA damage, senescence or apoptosis. Since cancer is frequently associated with aberrant cell cycle progression, defective DNA repair or apoptosis pathways, TRF2 could be one likely candidate for cancer therapy. Here we investigated the prognostic role of TRF2 levels in cervical cancer patients. Fold-induction rates were evaluated with respect to median values after real-time PCR analysis. Overall survival, distant disease-free and local recurrence-free survival rates were calculated using Kaplan-Meier long rank test. Results: Both five year overall-and disease-free survival rates were longer in patients with higher TRF2 expression compared to lower expression, but results were not statistically significant (69.2% vs 28.9%, respectively). Mean local recurrence-free survivals (LRF) were very close (58.6, CI: 44.3-72.9 vs 54.5, CI: 32.1-76.9 months) for high and low expressions, respectively. Cumulative proportion of LRF at the end of five year period was 76.9% for high and 57.1% for low TRF2 expression (P = 0.75). Statistically significant difference was found between survival ratios and Bcl-xL and p53 gene expressions, but not with TRF2. A respectable correlation between TRF2 expression and apoptosis along with distant metastasis was noted (P = 0.045 and 0.036, respectively). Additionally, high TRF2 expression levels had a positive impact in five year survival rate of stage IIIB-IVA patients (P = 0.04). Conclusions: Our results support the role of TRF2 in apoptosis and imply a positive relation with distant metastases and survival in advanced stage patients. The remarkable difference in survival periods of patients with different TRF2 expressions suggest that TRF2 may be a candidate factor to estimate survival for cervical cancer, a preliminary observation which should further be verified with a larger cohort
Synthesis of some novel hydrazide-hydrazones derived from etodolac as potential anti-prostate cancer agents
No full textSynthesis of the first mixed ligand Mn (II) and Cd (II) complexes of 4-methoxy-pyridine-2-carboxylic acid, molecular docking studies and investigation of their anti-tumor effects in vitro
No full textThe first mixed ligand Mn (II) and Cd (II) complexes containing 4-methoxy-pyridine-2-carboxylic acid (4-mpic) and 4,4 '-dimethyl-2,2 '-bipyridine (dmbpy) were synthesized in this study. The geometric structures of [Mn(4-mpic)(2)(dmbpy)] (complex 1) and [Cd(4-mpic)(2)(dmbpy)] (complex 2) were determined by single crystal X-Ray diffraction method. FT-IR and UV-Vis spectra were also recorded to investigate vibrational and electronic properties of complexes 1 and 2. Density functional theory (DFT) calculations were also carried out to provide a deep understanding in geometric, spectroscopic, electronic and nonlinear optical (NLO) properties of complexes 1 and 2. The first-order hyperpolarizibility (beta) parameter calculated as 332.9736 x 10(-30) esu demonstrated that complex 1 is an extremely promising candidate to NLO materials. Natural bond orbital (NBO) analysis not only verified the distorted octahedral geometries of central metal ions, but also found out the high-energy interactions responsible for biological activities for complexes 1 and 2. Anti-cancer activities of complexes 1 and 2 were tested on human breast carcinoma cell line MCF-7 (ER and PR positive, HER2 negative) and the triple negative breast carcinoma cell line MDA-MB 231 (ER, PR and HER2 negative). Dose-response relationship derived from MTT assays indicates that complexes 1 and 2 are showing concentration-dependent effects, which could suggest a potential use for these drug combinations in cancer cell lines
Effect of Bumetanide on Facial Nerve Regeneration in Rat Model
No full textObjective We investigated the effects of bumetanide alone and in combination with dexamethasone on facial nerve regeneration in rats with facial paralysis. Study Design A prospective controlled animal study. Setting An animal laboratory. Subjects and Methods Facial paralysis was induced in 32 Wistar rats that we then divided into 4 groups: group 1, control; group 2, bumetanide; group 3, dexamethasone; group 4, bumetanide and dexamethasone. Electroneurography was performed 1, 2, and 4 weeks later, and nerve regeneration was evaluated by electron and light microscopy and Western blotting in week 4. Results Regarding the comparison between preoperative values and week 4, the latency difference in group 1 (1.25 milliseconds) was significantly higher than those of groups 2 to 4 (0.56, 0.34, and 0.10 milliseconds, respectively;P= .001). The latency increment in groups 2 and 3 was higher than that of group 4 (P= .002 andP= .046) in week 4, whereas groups 2 and 3 did not differ significantly (P= .291). Amplitude difference was not statistically significant from week 4 among all groups (allP >.05). The number of myelinated axons was significantly higher in all treatment groups than in the control group (P= .001). Axon number and intensity were significantly higher in group 4 as compared with groups 2 and 3 (P= .009,P= .005). Conclusion After primary neurorrhaphy, dexamethasone and bumetanide alone promoted nerve recovery based on electrophysiologic and histologic measures. Combination therapy was, however, superior
Doxorubicin hydrochloride loaded nanotextured films as a novel drug delivery platform for ovarian cancer treatment
No full textAn approach for cancer treatment is modulation of tumor microenvironment. Based on the role of extracellular matrix in cell modulation, fabrication of textured materials mimicking extracellular matrix could provide novel opportunities such as determining cancer cell behaviour. With this background, in this work, we have fabricated doxorubicin hydrochloride loaded nanotextured films which promote topographical attachment of cancer cells to film surface, and eliminate cells by release of the anti-cancer drug encapsulated within the films. These films are designed to be placed during surgical removal of the tumor with the intent to prevent ovarian cancer recurrence by capturing cancer cell residuals. With this aim, hemispherical protrusion shaped surface textures were acquired using colloidal lithography technique using 280 nm, 210 nm or 99 nm polystyrene particles. Once moulds were formed, nanotextured films were obtained by casting water-in-oil stable polycaprolactone emulsions encapsulating doxorubicin hydrochloride. Films were then characterized, and evaluated as drug delivery systems. According to results, we found that template morphologies were successfully transferred to films by atomic force microscopy studies. Hydrophilic surfaces were formed with contact angle values around 40 degrees.In-vitrodrug release studies indicated that nanotextured films best fit into the Higuchi model, and similar to 30% of the drug is released from the films within 60 days. Cell culture results indicated increases in the attachment and viability of human ovarian cancer cells to nanotextured surfaces, particularly to the film fabricated using 99 nm particles. Our results demonstrated that delivery of anti-cancer drugs by use of nanotextured materials could be efficient in cancer therapy, and may offer new possibilities for cancer treatment
Biological effects of whole Z.Officinale extract on chronic myeloid leukemia cell line K562
No full text© 2019The anticancer activity of Zingiber officinalis (ginger) is an area of active research. However, data is quite limited regarding its action and mechanism, especially in hematologic cancer types. Here, antiproliferative and apoptotic effects of whole extract of the rhizome of Zingiber officinalis (ZOWE), was investigated in K562 cell line derived from a chronic myeloid leukemia (CML) patient. Various concentrations of whole extract (0, 10, 25, 50 and 100 μM) were tested in K562 cultures. Cytotoxicity and apoptosis was assessed with appropriate methods, as well as cellular ROS levels. In this study, we showed that ZOWE inhibited proliferation of K562 cells substantially, when compared to peripheral blood mononuclear cells (PBMCs) isolated from healthy donor. Increased Bax/Bcl-2 ratio, reduced mitochondrial membrane potential and increased PARP cleavage demonstrated that ZOWE inhibited proliferation by induction of apoptosis. These changes were coupled with an increase of reactive oxygen species (ROS) production. Furthermore, ZOWE addition to the culture also reduced expression levels of survival proteins pAkt and survivin, in a concentration dependent manner. Our results clearly mark that ZOWE causes to a reduction in cell viability, an induction of apoptosis and elevation in ROS levels in chronic myeloid leukemia cells and effects are significantly different from healthy peripheral blood mononuclear cells, further supporting its potential therapeutic value
Prognostic role of sensitive-to-apoptosis gene expression in rectal cancer
No full textAIM: To investigate the association between prognosis of rectal cancer treated with chemoradiotherapy (CRT) and expression of sensitive-to-apoptosis (SAG), B-cell lymphoma-extra large (Bcl-XL) and Bcl-2 homologous antagonist/killer (Bak). METHODS: Real-time quantitative polymerase chain reaction was used to determine the expression of proteins of interest, namely SAG, Bcl-XL, Bak and beta-actin, in rectal carcinoma patients who had a follow-up period of 3 years after CRT. Biopsy specimens were excised from the rectal tumor preceding CRT. RESULTS: SAG, Bcl-XL and Bak proteins showed significant correlations with each other. In multivariate analysis, patients with high vs low SAG expression showed a statistically significant difference in 2-year survival rates: 56% vs 73%, respectively (P = 0.056). On the other hand, there were no significant correlations between the expression levels of all three genes and metastatic rates or tumor responses to CRT. Mean overall survival in the patients with elevated SAG expression was 27.1 mo +/- 3.9 mo [95% confidence interval (CI): 19.3-34.9], and in patients with reduced expression, it was 32.1 mo +/- 2.5 mo (95% CI: 27.3-36.9). The corresponding values for Bcl-XL were 28.0 mo +/- 4.1 mo (95% CI: 19.9-36.1) and 31.7 mo +/- 2.9 mo (95% CI: 26.0-37.5), and those for Bak were 29.8 mo +/- 3.7 mo (95% CI: 22.5-37.2) and 30.6 mo +/- 2.4 mo (95% CI: 25.5-35.0), respectively. CONCLUSION: Two-year survival rates significantly correlated with low SAG expression, and SAG may be a candidate gene for good prognosis, independent of therapeutic response of different individuals. (C) 2011 Baishideng. All rights reserved
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