Browsing by Subject "Cyclin D1"

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    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.
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    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.
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    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.
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    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.