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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

Quantitative diffusion-weighted magnetic resonance imaging of normal and diseased uterine zones

Kilickesmez, O. | Bayramoglu, S. | Inci, E. | Cimilli, T. | Kayhan, A.

Article | 2009 | Acta Radiologica50 ( 3 ) , pp.340 - 347

Background: Magnetic resonance (MR) imaging has been established as the best imaging modality for the detection, localization, and staging of uterine cancers. Recently, the usefulness of diffusion-weighted imaging (DWI) in the diagnosis of cancers has been reported in several studies. Purpose: To calculate the apparent diffusion coefficient (ADC) values of normal uterine zones as well as benign and malignant uterine diseases, and to determine a cut-off ADC value for the quantitative detection of uterine malignancies with DWI. Material and Methods: Eighty-seven patients (mean age 53 years) with 107 benign and malignant uterine pathol . . .ogies and 50 healthy controls (mean age 38 years) were enrolled in the study. DWI was performed with b factors of 0, 500, and 1000 s/mm2. Results: The ADC values of benign and malignant lesions were compared using Student's t test. The mean and the standard deviation of the ADC values of the control group were as follows: myometrium 1.760.1910-3 mm2/s, junctional zone 0.990.1810-3 mm2/s, endometrium 1.650.3310-3 mm2/s, and cervix 1.710.1710-3 mm2/s. There was a statistically significant difference among the ADC values of normal myometrium and leiomyomas (1.470.3610-3 mm2/s; P0.009), endometrium and endometrial carcinomas (0.860.1310-3 mm2/s; P0.001), myometrium-junctional zone and adenomyosis (1.240.2010-3mm2/s; P0.001), and cervix and cervical carcinomas (0.910.1410-3 mm2/s; P0.001). The ADC values differed significantly between malignant (0.880.11) and benign lesions (1.550.33; P0.01). A cut-off value for malignant lesions of 1.0510-3 mm2/s yielded a sensitivity, specificity, and accuracy of 95.83%, 94.55%, and 94.94%, respectively. Conclusion: The present study shows that ADC measurements have the potential to quantitatively differentiate between normal and cancerous tissues of the uterine zones. We propose adding DWI as an adjunct sequence in the MR protocol for the assessment of uterine lesions. © 2009 Informa UK Ltd Daha fazlası Daha az

The bio-heat transfer equation and its applications in hyperthermia treatments

Tunç, M. | Çamdali, U. | Parmaksizoglu, C. | Çikrikçi, S.

Article | 2006 | Engineering Computations (Swansea, Wales)23 ( 4 ) , pp.451 - 463

Purpose - Cancer is the foremost disease that causes death. The objective of hyperthermia in cancer therapy is to raise the temperature of cancerous tissue above a therapeutic value while maintaining the surrounding normal tissue at sublethal temperature values in cases where surgical intervention is dangerous or impossible. The malignant tissue is heated up to 42°C in the treatment. In this method, the unaffected tissues are aimed to have minimum damage, while the affected ones are destroyed. Therefore, it is very important for the optimization of the method to know the temperature profiles in both tissues. Accurately estimating th . . .e tissue temperatures has been a very important issue for tumor hyperthermia treatment planning. This paper, proposes to theoretically predict the temperature response of the biological tissues subject to external EM heating by using the space-dependent blood perfusion term in Pennes bio-heat equation. Design/methodology/approach - The bio-heat transfer equation is parabolic partial differential equation. Grid points including independent variables are initially formed in solution of partial differential equation by finite element method. In this study, one dimensional bio-heat transfer equation is solved by flex-PDE finite element method. Findings - In this study, the bio-heat transfer equation is solved for variable blood perfusion values and the temperature field resulting after a hyperthermia treatment is obtained. Homogeneous, non-homogeneous tissue and constant, variable blood perfusion rates are considered in this study to display the temperature fields in the biological material exposed to externally induced electromagnetic irradiation. Originality/value - Temperature-dependent tissue thermophysical properties have been used and the Pennes equation is solved by FEM analysis. Variable blood perfusion and heat generation values have been used in calculations for healthy tissue and tissue with tumor. © Emerald Group Publishing Limited 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

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.5094 - 5102

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

Maslinic acid as an effective anticancer agent

Lin, X. | Ozbey, U. | Sabitaliyevich, U.Y. | Attar, Rukset | Ozcelik, B. | Zhang, Y. | Farooqi, A.A.

Article | 2018 | Cellular and Molecular Biology64 ( 10 ) , pp.87 - 91

Maslinic acid (2?,3ß-dihydroxyolean-12-en-28-oic acid) is a naturally occurring pentacyclic triterpenic compound. Maslinic acid is gradually gaining attention as an excellent pharmacologically active product because of its premium biological properties. In this review we will focus on chemopreventive properties of Maslinic acid against different cancers. Seemingly, available data is limited and we have yet to unravel how Maslinic acid therapeutically targeted oncogenic cell signal transduction cascades in different cancers. Moreover, there are visible knowledge gaps about the ability of Maslinic acid to modulate oncogenic and tumor . . .suppressor microRNAs in various cancers. © 2018 by the C.M.B. Association Daha fazlası Daha az

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