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- 저자 : Kallakury, B.V.S. (검색결과 4 건)
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Nakles, R.E.,Kallakury, B.V.S.,Furth, P.A. American Association of Pathologists and Bacteriol 2013 The American journal of pathology Vol.182 No.6
Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have anticancer activity and influence cell differentiation. We examined the impact of the selective PPARγ agonist efatutazone on mammary cancer pathogenesis in a mouse model of BRCA1 mutation. Mice with conditional loss of full-length BRCA1 targeted to mammary epithelial cells in association with germline TP53 insufficiency were treated with efatutazone through the diet starting at age 4 months and were euthanized at age 12 months or when palpable tumor reached 1 cm<SUP>3</SUP>. Although treatment did not reduce percentage of mice developing invasive cancer, it significantly reduced prevalence of noninvasive cancer and total number of cancers per mouse and increased prevalence of well-differentiated cancer subtypes not usually seen in this mouse model. Invasive cancers from controls were uniformly estrogen receptor α negative and undifferentiated, whereas well-differentiated estrogen receptor α-positive papillary invasive cancers appeared in efatutazone-treated mice. Expression levels of phosphorylated AKT and CDK6 were significantly reduced in the cancers developing in efatutazone-treated mice. Efatutazone treatment reduced rates of mammary epithelial cell proliferation and development of hyperplastic alveolar nodules and increased expression levels of the PPARγ target genes Adfp, Fabp4, and Pdhk4 in preneoplastic mammary tissue. Intervention efatutazone treatment in mice with BRCA1 deficiency altered mammary cancer development by promoting development of differentiated invasive cancer and reducing prevalence of noninvasive cancer and preneoplastic disease.
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Baek, Hye Jung,Pishvaian, Michael J.,Tang, Yi,Kim, Tae Hyun,Yang, Shaoxian,Zouhairi, Majed El,Mendelson, Jon,Shetty, Kirti,Kallakury, Bhaskar,Berry, Deborah L.,Shin, Kyung Hwan,Mishra, Bibhuti,Reddy, Wiley Subscription Services, Inc., A Wiley Company 2011 Hepatology Vol.53 No.5
<P><B>Abstract</B></P><P>Transforming growth factor beta (TGF‐β) is an important regulator of cell growth, and loss of TGF‐β signaling is a hallmark of carcinogenesis. The Smad3/4 adaptor protein β2‐spectrin (β2SP) is emerging as a potent regulator of tumorigenesis through its ability to modulate the tumor suppressor function of TGF‐β. However, to date the role of the TGF‐β signaling pathway at specific stages of the development of hepatocellular carcinoma (HCC), particularly in relation to the activation of other oncogenic pathways, remains poorly delineated. Here we identify a mechanism by which β2SP, a crucial Smad3 adaptor, modulates cyclin dependent kinase 4 (CDK4), cell cycle progression, and suppression of HCC. Increased expression of β2SP inhibits phosphorylation of the retinoblastoma gene product (Rb) and markedly reduces CDK4 expression to a far greater extent than other CDKs and cyclins. Furthermore, suppression of CDK4 by β2SP efficiently restores Rb hypophosphorylation and cell cycle arrest in G<SUB>1</SUB>. We further demonstrate that β2SP interacts with CDK4 and Smad3 in a competitive and TGF‐β‐dependent manner. In addition, haploinsufficiency of <I>cdk4</I> in <I>β2sp</I><SUP><I>+/−</I></SUP> mice results in a dramatic decline in HCC formation compared to that observed in <I>β2sp</I><SUP><I>+/−</I></SUP> mice. <I>Conclusion</I>: β2SP deficiency leads to CDK4 activation and contributes to dysregulation of the cell cycle, cellular proliferation, oncogene overexpression, and the formation of HCCs. Our data highlight CDK4 as an attractive target for the pharmacologic inhibition of HCC and demonstrate the importance of <I>β2sp</I><SUP>+/−</SUP> mice as a model of preclinical efficacy in the treatment of HCC. (H<SMALL>EPATOLOGY</SMALL> 2011;)</P>
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Nuclear Factor (Erythroid-Derived 2)-Like 2 Regulates Drug Resistance in Pancreatic Cancer Cells
Hong, Young Bin,Kang, Hyo Jin,Kwon, Sun Young,Kim, Hee Jeong,Kwon, Kun Young,Cho, Chi Heum,Lee, Jong-Min,Kallakury, Bhaskar V.S.,Bae, Insoo Lippincott Williams Wilkins, Inc. 2010 PANCREAS Vol.39 No.4
OBJECTIVE:: To investigate the molecular basis of drug resistance in pancreatic cancer. METHODS:: The expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) levels in pancreatic cancer tissues and cell lines was analyzed. Clinical relevance between Nrf2 activation and drug resistance was demonstrated by measuring cell viability after Nrf2 and adenosine 5&vprime;-triphosphate-binding cassette, subfamily G member 2 (ABCG2) regulation by overexpression or knock-down of these genes. Activity of ABCG2 was measured by Hoechst 33342 staining. RESULTS:: Abnormally elevated Nrf2 protein levels were observed in pancreatic cancer tissues and cell lines relative to normal pancreatic tissues. Increasing Nrf2 protein levels either by overexpression of exogenous Nrf2 or by activating endogenous Nrf2 resulted in increased drug resistance. Conversely, a reduction in endogenous Nrf2 protein levels or inactivation of endogenous Nrf2 resulted in decreased drug resistance. These changes in drug resistance or sensitivity were also positively correlated to the expression levels of Nrf2 downstream genes. Similarly, the expression of ABCG2 was correlated with drug resistance. CONCLUSIONS:: Because the intrinsic drug resistance of pancreatic cancers is, in part, due to abnormally elevated Nrf2 protein levels, further research on regulating Nrf2 activity may result in the development of novel pancreatic cancer therapies.
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Comparison of Classification Techniques to Detect Snow Images
Sankalp Kallakuri,Jitesh K. Singh,Roh Seung Hyun 한국자동차공학회 2011 한국자동차공학회 학술대회 및 전시회 Vol.2011 No.11
Modern day vehicles have several safety and convenience features. One such feature is weather detection. Detection of snow using a camera in a vehicle is one of the means to detect the snow. Thus there is a need to classify images taken from an onboard camera into images with snow and images without snow. Based on such classification the electronic control unit of the vehicle can automatically activate wipers and head lights of the vehicle in an appropriate manner to handle the inclement weather. This classification has been attempted using Support Vector Machines and K Nearest Neighbor Classifiers. This paper presents a comparison of the above mentioned methods in terms of their accuracy and their False Acceptance Rates (FAR). The feature based on which the image classification has been done is the histogram of the image.
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