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Genotoxic effects of PCB 52 and PCB 77 on cultured human peripheral lymphocytes

Sandal, S. | Yılmaz, B. | Carpenter, D.O.

Article | 2008 | Mutation Research - Genetic Toxicology and Environmental Mutagenesis654 ( 1 ) , pp.88 - 92

Polychlorinated biphenyls (PCBs) are known to be carcinogenic, but the mechanisms of this action are uncertain. Most, but not all, studies have concluded that PCBs are not directly mutagenic, and that much if not all of the carcinogenic activity resides in the fraction of the PCB mixture that contains congeners with dioxin-like activity. The present study was designed to determine genotoxic effects of an ortho-substituted, non-coplanar congener, 2,2',5,5'-tetrachlorobiphenyl (PCB 52), and a non-ortho-substituted coplanar congener with dioxin-like activity, 3,3',4,4'-tetrachlorobiphenyl (PCB 77) on cultured human peripheral lymphocyt . . .es. DNA damage was assessed by use of the comet assay (alkaline single-cell gel electrophoresis). After cell cultures were prepared, test groups were treated with different concentrations of PCB 52 (0.2 and 1 µM) and PCB 77 (1 and 10 µM) for 1 h at 37 °C in a humidified carbon dioxide incubator, and compared to a DMSO vehicle control group. The cells were visually classified into four categories on the basis of extent of migration such as undamaged (UD), low damage (LD), moderate damage (MD) and high damage (HD). The highest concentration of PCBs 52 and 77 significantly increased DNA breakage in human lymphocytes (p < 0.001). Our results indicate that both the non-coplanar PCB 52 and coplanar PCB 77 cause DNA damage, and that the ortho-substituted congener was significantly more potent than the dioxin-like coplanar congener. © 2008 Elsevier B.V. All rights reserved Daha fazlası Daha az

Hydrogen peroxide prolongs mitotic arrest in a dose dependent manner and independently of the spindle assembly checkpoint activity in saccharomyces cerevisiae

Atalay, P.B. | Asci, O. | Kaya, F.O. | Tuna, B.G.

Article | 2017 | Acta Biologica Hungarica68 ( 4 ) , pp.477 - 489

Oxidative stress and chromosome missegregation are important factors that are linked to aneuploidy. A major reason for chromosome missegragation is the inappropriate activity of the spindle assembly checkpoint (SAC), a conserved surveillance mechanism that monitors the state of kinetochore-microtubule attachments to ensure equal chromosome segregation in mitosis. SAC-activation induces a prolonged mitotic arrest. Mitosis is considered the most vulnerable cell cycle phase to several external signals, therefore increasing the time cells spent in this phase via mitotic arrest induction by SAC-activating agents is favorable for cancer t . . .herapy. Cancer cells also display elevated oxidative stress due to abnormally high production of reactive oxygen species (ROS). However, the effect of increased oxidative stress on the duration of mitotic arrest remains largely unknown. In this study, we investigated the effect of H 2 O 2 -induced oxidative stress on the mitotic arrest induced by a SAC-activating agent (nocodazole) in Saccharomyces cerevisiae. Our data suggest that oxidative stress prolongs SAC-activation induced mitotic arrest in a dose dependent manner. We, in addition, investigated the effect of H 2 O 2 treatment on the mitotic arrest induced independently of SAC-activation by using a conditional mutant (cdc23) and showed that the effect of H 2 O 2 -induced oxidative stress on mitotic arrest is independent of the SAC activity. © 2017 Akademiai Kiado Rt. All rights reserved Daha fazlası Daha az

Development and characterization of liposomal formulations for rapamycin delivery and investigation of their antiproliferative effect on MCF7 cells

Rouf, M.A. | Vural, I. | Renoir, J.M. | Hincal, A.A.

Article | 2009 | Journal of Liposome Research19 ( 4 ) , pp.322 - 331

Rapamycin (Sirolimus) is a macrolide lactone with antifungal, immunosuppressant, and antiproliferative actions. The mechanism of rapamycin action involves the inhibition of mTOR and subsequent cytostasis. Rapamycin also prevents angiogenesis in tumors and can prevent cancer cells' resistance to other chemotherapeutic agents. However, very poor water solubility, bioavailability, only slight solubility in acceptable parenteral excipients, chemical instability, and major sequestration (95%) of free rapamycin into the erythrocytes have prevented its development as an anticancer drug. To address these problems, it was attempted to develo . . .p liposomal rapamycin delivery systems in this study. Conventional and pegylated liposomes were prepared with various lipid and cholesterol ratios. They were then characterized; these liposomes contained 0.680.90mg of rapamycin per milliliter of liposome suspension. Having suitable particle size, these liposomes successfully retained the entrapped drug. Both types of liposomes were found to be effective; however, conventional liposomes showed better antiproliferative activity against MCF-7 cells than pegylated liposomes. But, pegylated liposome showed better stability than conventional liposomes. In conclusion, the enhanced permeability and retention effercts of tumors should provide the opportunity for pegylated liposomal rapamycin to be applied as an intravenous drug-delivery system for targeted delivery to cancer cells, avoiding the major sequestration of free rapamycin into the erythrocytes Daha fazlası Daha az

Diagnostic utility of DTI in prostate cancer

Gürses, B. | Tasdelen, N. | Yencilek, F. | Kilickesmez, N.O. | Alp, T. | Firat, Z. | Gürmen, A.N.

Article | 2011 | European Journal of Radiology79 ( 2 ) , pp.172 - 176

Purpose: The aim of this study was to compare the diffusion tensor parameters of prostate cancer, prostatitis and normal prostate tissue. Materials and Methods: A total of 25 patients with the suspicion of prostate cancer were included in the study. MRI was performed with 3 T system (Intera Achieva, Philips Medical Systems, The Netherlands). T2 TSE and DTI with ss-EPI were obtained in each subject. TRUS-guided prostate biopsy was performed after the MRI examination. Images were analyzed by two radiologists using a special software system. ROI's were drawn according to biopsy zones which are apex, midgland, base and central zone on e . . .ach sides of the gland. FA and ADC values in areas of cancer, chronic prostatitis and normal prostate tissue were compared using Student's t-test. Results: Histopathological analysis revealed carcinoma in 68, chronic prostatitis in 67 and was reported as normal in 65 zones. The mean FA of cancerous tissue was significantly higher (p < 0.01) than the FA of chronic prostatitis and normal gland. The mean ADC of cancerous tissue was found to be significantly lower (p < 0.01), compared with non-cancerous tissue. Conclusion: Decreased ADC and increased FA are compatible with the hypercellular nature of prostate tumors. These differences may increase the accuracy of MRI in the detection of carcinoma and to differentiate between cancer and prostatitis. © 2010 Elsevier Ireland Ltd Daha fazlası Daha az

Lactose-modified DNA tile nanostructures as drug carriers

Akkus Sut, P. | Tunc, C.U. | Çulha, Mustafa

Article | 2016 | Journal of Drug Targeting24 ( 8 ) , pp.709 - 719

Abstract: Background: DNA hybridization allows the preparation of nanoscale DNA structures with desired shape and size. DNA structures using simple base pairing can be used for the delivery of drug molecules into the cells. Since DNA carries multiple negative charges, their cellular uptake efficiency is low. Thus, the modification of the DNA structures with molecules that may enhance the cellular internalization may be an option. Objective: The objective of this study is to construct DNA-based nanocarrier system and to investigate the cellular uptake of DNA tile with/without lactose modification. Methods: Doxorubicin was intercalate . . .d to DNA tile and cellular uptake of drug-loaded DNA-based carrier with/without lactose modification was investigated in vitro. HeLa, BT-474, and MDA-MB-231 cancer cells were used for cellular uptake studies and cytotoxicity assays. Using fluorescence spectroscopy, flow cytometry, and confocal microscopy, cellular uptake behavior of DNA tile was investigated. The cytotoxicity of DNA tile structures was determined with WST-1 assay. Results: The results show that modification with lactose effectively increases the intracellular uptake of doxorubicin loaded DNA tile structure by cancer cells compared with the unmodified DNA tile. Conclusion: The findings of this study suggest that DNA-based nanostructures modified with carbohydrates can be used as suitable multifunctional nanocarriers with simple chemical modifications. © 2016 Informa UK Limited, trading as Taylor & Francis Group Daha fazlası Daha az

A novel thiazolidine compound induces caspase-9 dependent apoptosis in cancer cells

Onen-Bayram, F.E. | Durmaz, I. | Scherman, D. | Herscovici, J. | Cetin-Atalay, R.

Article | 2012 | Bioorganic and Medicinal Chemistry20 ( 17 ) , pp.5094 - 5102

The forward chemogenomics strategy allowed us to identify a potent cytotoxic thiazolidine compound as an apoptosis-inducing agent. Chemical structures were designed around a thiazolidine ring, a structure already noted for its anticancer properties. Initially, we evaluated these novel compounds on liver, breast, colon and endometrial cancer cell lines. The compound 3 (ALC67) showed the strongest cytotoxic activity (IC50 ~5 µM). Cell cycle analysis with ALC67 on liver cells revealed SubG1/G1 arrest bearing apoptosis. Furthermore we demonstrated that cytotoxicity of this compound was due to the activation of caspase-9 involved apoptot . . .ic pathway, which is death receptor independent. © 2012 Elsevier Ltd. All rights reserved Daha fazlası Daha az

Flexible ureterorenoscopic management of upper tract pathologies

Papatsoris, A. | Sarica, K.

Review | 2012 | Urological Research40 ( 6 ) , pp.639 - 646

The last decade flexible ureteroscopy has progressed from an awkward diagnostic procedure with limited visualization to a precise surgical intervention allowing access to the entire collecting system. In this review, we present the current status and future perspectives of the ureterorenoscopic management of urolithiasis and nonstone- related upper tract pathologies. © Springer-Verlag 2012.

Recent updates on true potential of an anesthetic agent as a regulator of cell signaling pathways and non-coding RNAs in different cancers: Focusing on the brighter side of propofol

Farooqi, A.A. | Adylova, A. | Sabitaliyevich, U.Y. | Attar, Rukset | Sohail, M.I. | Yilmaz, S.

Review | 2020 | Gene737 , pp.639 - 646

There has always been a quest to search for synthetic and natural compounds having premium pharmacological properties and minimum off-target and/or side effects. Therefore, in accordance with this approach, scientists have given special attention to the molecules having remarkable ability to target oncogenic protein network, restore drug sensitivity and induce apoptosis in cancer cells. The mechanisms through which general anesthetics modulated wide-ranging deregulated cell signaling pathways and non-coding RNAs remained unclear. However, rapidly accumulating experimentally verified evidence has started to resolve this long-standing . . . mystery and a knowledge about these important molecular targets has surfaced and how these drugs act at the molecular level is becoming more understandable. In this review we have given special attention to available evidence related to ability of propofol to modulate Wnt/ß-catenin, JAK/STAT and mTOR-driven pathway. Excitingly, great strides have been made in sharpening our concepts related to potential of propofol to modulate non-coding RNAs in different cancers. Collectively, these latest findings offer interesting, unexplored opportunities to target deregulated signaling pathways to induce apoptosis in drug-resistant cancers. © 2020 Elsevier B.V Daha fazlası Daha az

Safety, feasibility, and efficacy of capecitabine maintenance in patients with advanced gastric cancer: A retrospective study

Eren, O.O. | Ozturk, M.A. | Sonmez, O.U. | Oyan, B.

Article | 2016 | American Journal of Therapeutics23 ( 6 ) , pp.639 - 646

Gastric cancer is still one of the cancers with highest mortality. Most patients present with advancedstage disease. Palliative chemotherapy is usually the only treatment option for patients with advanced gastric cancer (AGC). Maintenance chemotherapy is an evolving concept in medical oncology. Maintenance chemotherapy can be administered with the same drug(s) in the initial regimen or with an alternative agent. In this article, we report our experience with capecitabine as a maintenance agent for patients with AGC. No treatment-related death was observed due to use of capecitabine. Median progression-free survival was 10.4 months, . . .and median overall survival was 19.7 months. Activity and toxicity profile of capecitabine seems favorable as a maintenance agent in AGC. We believe that capecitabine deserves further trials as a maintenance agent for patients with AGC. Copyright © 2015 Wolters Kluwer Health, Inc Daha fazlası Daha az

Reliability and Validity of Turkish Version of the Caregiver Quality of Life Index Cancer Scale

Yakar, H.K. | Pinar, R.

Article | 2013 | Asian Pacific Journal of Cancer Prevention14 ( 7 ) , pp.4415 - 4419

Background: Measuring effects of cancer on family caregivers is important to develop methods which can improve their quality of life (QOL). Nevertheless, up to now, only a few tools have been developed to be used in this group. Among those, the Caregiver Quality of Life Index-Cancer Scale (CQOLC) has met minimum psychometric criteria in different populations in spite of conflicting results. The present study was conducted to evaluate reliability and validity of CQOLC among Turkish cancer family caregivers. Materials and Methods: The CQOLC was administered to 120 caregivers, along with Beck Depression Inventory (BDI), Medical Outcome . . .s Study MOS 36- Item Short Form Health Survey (SF-36), State-Trait Anxiety Inventory (STAI), and Multidimensional Scale of Perceived Social Support (MSPSS). Internal consistency and test-retest stability were used to investigate reliability. Construct validity was examined by using known group method, convergent, and divergent validity. For the known group method, we hypothesized that CQOLC scores would differ between depressed and non-depressed subjects. We investigated convergent validity by correlating scores for CQOLC with scores for other similar measures including SF-36 and STAI. The MSPSS was completed at the same time as CQOLC to provide divergent validity. Results: The values for internal consistency and test-retest correlation were 0.88 and 0.96, respectively. The CQOLC discriminated those who were depressed from those who were not. Convergent validity supported strong correlations between CQOLC scores and two main component scores (PCS, MCS) in SF-36 although there was a weak correlation between CQOLC and STAI scores. Regarding divergent validity, the correlation between CQOLC and MSPSS was in the low range, as expected. Conclusions: The Turkish CQOLC is a reliable and valid tool and it can be utilized to determine QOL of family caregivers Daha fazlası Daha az

Cancer cell Cytotoxicities of 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivatives

Yarim, M. | Koksal, M. | Durmaz, I. | Atalay, R.

Article | 2012 | International Journal of Molecular Sciences13 ( 7 ) , pp.8071 - 8085

A series of novel 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivatives 5a-g was designed by a nucleophilic substitution reaction of 1-(4-chlorobenzhydryl)piperazine with various benzoyl chlorides and characterized by elemental analyses, IR and 1H nuclear magnetic resonance spectra. Cytotoxicity of the compounds was demonstrated on cancer cell lines from liver (HUH7, FOCUS, MAHLAVU, HEPG2, HEP3B), breast (MCF7, BT20, T47D, CAMA-1), colon (HCT-116), gastric (KATO-3) and endometrial (MFE-296) cancer cell lines. Time-dependent cytotoxicity analysis of compound 5a indicated the long-term in situ stability of this compoun . . .d. All compounds showed significant cell growth inhibitory activity on the selected cancer cell lines. © 2012 by the authors; licensee MDPI, Basel, Switzerland Daha fazlası Daha az

Tudor tells about new twists in the story tale of SMURFs

Qureshi, M.Z. | Jabeen, S. | Butt, G. | Aslam, A. | Naqvi, S.K.-U.-H. | Attar, Rukset | Farooqi, A.A.

Review | 2016 | Cellular and Molecular Biology62 ( 5 ) , pp.38 - 43

Smad ubiquitin regulatory factors (SMURFS) belong to the HECT- family of E3 ubiquitin ligases. This family has two members, SMURF1 and SMURF2. SMURFs have emerged as well studied negative regulators of TGF induced intracellular signaling. However, increasingly it is being realized that SMURFs tactfully modulate an array of proteins in different cancers. This review sets spotlight on how SMURF1 and SMURF2 communicate with effectors of different signaling pathways during the multistep progression to cancer. We also summarize how microRNAs (miRNAs) effectively control SMURFs in different cancers. Role of SMURFs is context dependent in . . .different cancers and better concepts related to miRNA regulation of SMURFs in different stages and steps of cancer will be helpful in efficient translation of laboratory findings to clinic. © 2016 by the C.M.B. Association. All rights reserved Daha fazlası Daha az

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