Browsing by Subject "cyclin D1"
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Item Histopathological and immunohistochemical features of 32 cases of splenic B-cell lymphoma and leukemia(Turkiye Klinikleri, 2009) Kaçar Döger F.; Hekimgil M.; Ertan Y.; Sarsik B.; Soydan S.; Neşe N.Objective: Leukemias and non-Hodgkin lymphomas commonly involve the spleen or originate primarily in the spleen and then spread to other sites. Material and Methods: In this retrospective study, we examined the histopathological and immunohistochemical characteristics of 32 cases of primary or secondary splenic B-cell lymphoma and leukemia, in which the diagnosis was established according to the World Health Organization (WHO) classification. The immunohistochemical panel included ALK-1, BCL-2, BCL-6, CD3, CD5, CD10, CD20, CD21, CD23, CD30, CD43, cyclin D1, Ki-67, and TRAP. Results: There was no other nodal or extranodal disease involvement in the majority of patients diagnosed with lymphoma at the time of presentation, while cases of leukemia had undergone splenectomy for palliative purposes. The diagnoses were as follows: 11 cases of hairy cell leukemia (HCL, 34.4%), 8 cases of splenic marginal zone lymphoma (SMZL, 25%), 8 cases of diffuse large B-cell lymphoma (DLBCL, 25%) including 1 T-cell-rich B-cell lymphoma (TCRBCL), 4 cases of mantle cell lymphoma (MCL, 12.5%), and 1 prolymphocytic leukemia (PLL, 3.1%). Conclusion: Overall assessment of spleen, liver, bone marrow, and lymph node examinations and a detailed correlation of the histopathological and immunohistochemical features with the clinical findings are very helpful and usually lead to the final diagnosis in most cases of primary or secondary splenic B-cell lymphoma and leukemia. Copyright © 2009 by Türkiye Klinikleri.Item The role of pRB, p16 and cyclin D1 in colonic carcinogenesis(2010) Ayhan S.; Isisag A.; Saruc M.; Nese N.; Demir M.A.; Kucukmetin N.T.Background/ Aims: This study is aimed to investigate abnormal expression of the Rb protein (pRb), p16INK4a (p16) and cyclin D1 in colorectal adenomas and adenocarcinomas and to assess the possible alterations in Rb pathway in colorectal carcinogenesis. METHODOLOGY: 44 cases of colorectal adenoma and 44 cases of colorectal adenocarcinoma were examined histopathologically and immunohistochemically using monoclonal antibodies to identify abnormalities of pRb, p16, and cyclin D1 expression. Staining degree of above-mentioned markers was assessed by using a semi-quantitative method in all cases in order to determine any staining differences. RESULTS: In 70.5% of the adenomas and 97.7% of the adenocarcinomas, an overexpression of pRb was found. There was a statistically significant relationship between the immunoreactivity of pRb and villous/ tubulovillous types of adenomas (p<0.05). There was a loss of p16 expression in 84.1% of adenomas and 61.4% of adenocarcinomas. Statistically significantly, the p16 overexpression was not seen in any of tubular adenomas (p<0.001). Overexpression of cyclin D1 was found in only 9.1% of adenomas, while 31.8% of adenocarcinomas overexpressed this protein. Loss of expression of cyclin D1 was similar in adenomas and adenocarcinomas (27.3% and 25%, respectively). Staining degrees of all three cell cycle proteins were shown to be statistically different in adenomas and adenocarcinomas, for pRb (p=0.001), for p16 (p=0.045), and cyclin D1 (p=0.05). Also, there was only a mild agreement with respect to p16 and cyclin D1 relationship between for adenomas (K=+0,28 p=0,051) and for adenocarcinomas (K=+0,35 p=0,017). Besides, there was no correlation between the expression of pRb, p16, and cyclin D1 and clinicopathological tumor characteristics and prognostic data such as stage or lymph node/liver metastasis. CONCLUSIONS: pRb, p16 and cyclin D1 are shown to be aberrantly expressed in both colorectal adenomas and adenocarcinomas. It can be claimed that disturbances in Rb pathway take part in colonic carcinogenesis and pRb, p16 and cyclin D1 play an ever increasing role in the further stages of adenoma-carcinoma sequence. © H.G.E. Update Medical Publishing S.A.Item Effects of isotretinoin on spermatogenesis of rats(2011) Gencoglan G.; Tosun M.Background: The results of studies on the effects of retinoids on spermatogenesis are controversial. Objectives: We evaluated time- and dose-dependent effects of isotretinoin on spermatogenic activity by apoptosis, cyclin D1, E2F, p53 expressions, and Johnsen's scores. Methods: The rats were divided into three groups. In the 1st group (n=18), 1mg/mL/day and in the 2nd group (n=18) 2mg/mL/day isotretinoin were administered for 21 days. Flower oil was given to the 3rd (n=6) control group. On the 7th (groups 1a and 2a), 14th (groups 1b and 2b), and 21st (groups 1c and 2c) days, six rats from the 1st group and six rats from the 2nd group were sacrificed and bilateral orchiectomy was done. Results: The number of cyclin D1 and E2F-positive cells decreased nonsignificantly parallel to days in the 1st group, whereas there was a statistically significant decrease in the 2nd group for the same cells. The p53-positive cells in groups 1c and 2c were increased significantly. Conclusions: Further studies on the effects of retinoids on spermatogenesis should be conducted. It may be wise to administer contraception to male patients, especially during high-dose and long-term retinoid therapy. © 2011 Informa Healthcare USA, Inc.Item Determination of apoptosis and cell cycle modulators (p16, p21, p27, p53, BCL-2, Bax, BCL-XL, and cyclin D1) in thyroid follicular carcinoma, follicular adenoma, and adenomatous nodules via a tissue microarray method(Turkiye Klinikleri, 2015) Temiz P.; Akkaş G.; Neşe N.; Uğur Duman F.; Karakaş C.; Erhan Y.Background/aim: To identify the role of gene products associated with apoptosis and cell cycle in the pathogenesis of thyroid follicular neoplasm. Materials and methods: Thirty follicular adenomas (FAs), 16 follicular carcinomas (FCs), and 20 adenomatous nodules (ANs) were investigated with immunohistochemical staining of p16, p21, p27, p53, Bcl-2, Bax, Bcl-xL, and cyclin D1 via a tissue microarray method. Results: Bcl-2 showed a significant difference between the benign groups (AN and FA) and the malignant group (FC). Bax was significantly higher in the FC group. p53 was lowest in the AN group and highest in the FC group with significant differences between the groups. p16 was significantly higher in the FC group than in the other groups. There was a significant difference between the AN group and neoplastic lesions in terms of p21 staining. The number of cases with positive p27 was lower in the AN group than the neoplastic groups. There was no significant difference in terms of Bcl-xL and cyclin D1. Conclusion: Cell cycle modulators, led by the Bcl-2 family, played an important role in the pathogenesis of thyroid follicular neoplasm, and p53, p16, and p21 in particular played a role in the carcinogenesis of FC. © TÜBİTAK.Item Loss of Wasl improves pancreatic cancer outcome(American Society for Clinical Investigation, 2020) Hidalgo-Sastre A.; Desztics J.; Dantes Z.; Schulte K.; Ensarioglu H.K.; Bassey-Archibong B.; Öllinger R.; Engleiter T.; Rayner L.; Einwächter H.; Daniel J.M.; Altaee A.S.A.; Steiger K.; Lesina M.; Rad R.; Reichert M.; Von Figura G.; Siveke J.T.; Schmid R.M.; Lubeseder-Martellato C.Several studies have suggested an oncogenic role for the neural Wiskott-Aldrich syndrome protein (N-WASP, encoded by the Wasl gene), but thus far, little is known about its function in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed in silico analysis of WASL expression in PDAC patients and found a correlation between low WASL expression and prolonged survival. To clarify the role of Wasl in pancreatic carcinogenesis, we used 2 oncogenic Kras-based PDAC mouse models with pancreas-specific Wasl deletion. In line with human data, both mouse models had an increased survival benefit due to either impaired tumor development in the presence of the tumor suppressor Trp53 or the delayed tumor progression and senescent phenotype upon genetic ablation of Trp53. Mechanistically, loss of Wasl resulted in cell-autonomous senescence through displacement of the N-WASP binding partners WASP-interacting protein (WIP) and p120ctn; vesicular accumulation of GSK3β, as well as YAP1 and phosphorylated β-catenin, which are components of the destruction complex; and upregulation of Cdkn1a(p21), a master regulator of senescence. Our findings, thus, indicate that Wasl functions in an oncogenic manner in PDAC by promoting the deregulation of the p120-catenin/β-catenin/p21 pathway. Therefore, strategies to reduce N-WASP activity might improve the survival outcomes of PDAC patients. © 2020, American Society for Clinical Investigation.Item Origanum Sipyleum Methanol Extract in Combination with Ponatinib Shows Synergistic anti-Leukemic Activities on Chronic Myeloid Leukemia Cells(Taylor and Francis Ltd., 2022) Kayabasi C.; Yilmaz Susluer S.; Balci Okcanoglu T.; Ozmen Yelken B.; Mutlu Z.; Goker Bagca B.; Caliskan Kurt C.; Saydam G.; Durmuskahya C.; Kayalar H.; Ozbilgin A.; Biray Avci C.; Gunduz C.Origanum sipyleum is used in folk medicine due to its anti-inflammatory, antimicrobial, and antioxidant properties. Ponatinib, an effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML), has severe side effects. Thus, we aimed to determine a novel herbal combination therapy that might not only increase the anti-leukemic efficacy but also reduce the dose of ponatinib in targeting CML cells. Origanum sipyleum was extracted with methanol (OSM), and secondary metabolites were determined by phytochemical screening tests. The cytotoxic effects of OSM on K562 cells were measured by WST-1 assay. Median-effect equation was used to analyze the combination of ponatinib and OSM (p-OSM). Apoptosis, proliferation, and cell-cycle were investigated by flow-cytometry. Cell-cycle-related gene expressions were evaluated by qRT-PCR. OSM that contains terpenoids, flavonoids, tannins, and anthracenes exhibited cytotoxic effects on K562 cells. The median-effect of p-OSM was found as synergistic; OSM reduced the ponatinib dose ∼5-fold. p-OSM elevated the apoptotic and anti-proliferative activity of ponatinib. Consistently, p-OSM blocked cell-cycle progression in G0/G1, S phases accompanied by regulations in TGFB2, ATR, PP2A, p18, CCND1, CCND2, and CCNA1 expressions. OSM enhanced the anti-leukemic activity of ponatinib synergistically via inducing apoptosis, suppressing proliferation, and cell-cycle. As a result, OSM might offer a potential strategy for treating patients with CML. © 2022 Taylor & Francis Group, LLC.Item N-Propargylic β-enaminones in breast cancer cells: Cytotoxicity, apoptosis, and cell cycle analyses(John Wiley and Sons Inc, 2023) Ilhan S.; Atmaca H.; Yilmaz E.S.; Korkmaz E.; Zora M.Breast cancer is one of the most common cancers worldwide and the discovery of new cytotoxic agents is needed. Enaminones are regarded to be a significant structural motif that is found in a variety of pharmacologically active compounds however the number of studies investigating the anticancer activities of N-propargylic β-enaminones (NPEs) is limited. Herein we investigated the potential cytotoxic and apoptotic effects of 23 different NPEs (1-23) on human breast cancer cells. Cytotoxicity was evaluated via MTT assay. Apoptotic cell death and cell cycle distributions were investigated by flow cytometry. CM-H2DCFDA dye was used to evaluate cellular ROS levels. Expression levels of Bcl-2, Bax, p21, and Cyclin D1 were measured by quantitative real-time PCR. ADME properties were calculated using the ADMET 2.0 tool. NPEs 4, 9, 16, and 21 showed selective cytotoxic activity against breast cancer cells with SI values >2. NPEs induced apoptosis and caused significant changes in Bcl-2 and Bax mRNA levels. The cell cycle was arrested at the G0/G1 phase and levels of p21 and Cyclin D1 were upregulated in both breast cancer cells. ROS levels were significantly increased by NPEs, suggesting that the cytotoxic and apoptotic effects of NPEs were mediated by ROS. ADME analysis revealed that NPEs showed favorable distributions in both breast cancer cell lines, meaning good lipophilicity values, low unfractionated values, and high bioavailability. Therefore, these potential anticancer compounds should be further validated by in vivo studies for their appropriate function in human health with a safety profile, and a comprehensive drug interaction study should be performed. © 2023 Wiley Periodicals LLC.Item Bioevaluation of Spiro N-Propargylic β-Enaminones as Anti-Breast Cancer Agents: In Vitro and Molecular Docking Studies(John Wiley and Sons Inc, 2023) Atmaca H.; Ilhan S.; Dundar B.A.; Zora M.The study aimed to investigate the in vitro inhibitory activities of spiro N-propargylic β-enaminones, SPEs 1-31, against BCa cells, to perform in silico molecular docking studies to understand the nature of the interaction between the compounds and the ERα, PR, EGFR, and Her2, and to determine the ADMET and drug-likeness properties. Cytotoxic activity was investigated via MTT assay. DNA fragmentation was evaluated via ELISA assay. Cell cycle distributions were investigated by flow cytometry. Expression levels of Bcl-2, Bax, p21 and Cyclin D1 were measured by qRT-PCR and western blot analysis. Molecular docking was done using Autodock/vina software. ADMET analysis was calculated using the ADMETlab 2.0 tool. SPEs 1, 22, and 28 showed selective cytotoxic activity against all BCa cells with SI values >2. SPEs induced apoptosis and caused significant changes in Bcl-2 and Bax levels. The cell cycle was arrested at the S phase and levels of p21 and Cyclin D1 were induced in all BCa cells. Molecular docking analysis revealed that SPE1, SPE22, and SPE28 showed high binding affinities with ERα, PR, EGFR, and Her2. ADMET analysis revealed that SPEs are drug-like compounds as they obey the five rules of Lipinsky and are not toxic. Therefore, these potential anticancer compounds should be further validated by in vivo studies for their appropriate function in human health with a safety profile, and a comprehensive drug interaction study should be performed. © 2023 Wiley-VHCA AG, Zurich, Switzerland.