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Раковая наука и терапия

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Объем 5, Проблема 1 (2013)

исследовательская статья

Gene Expression Profiling from a Prostate Cancer PC-3 Cell Line Treated with Salinomycin Predicts Cell Cycle Arrest and Endoplasmic Reticulum Stress

Kwang-Youn Kim, Young-Kyo Seo, Sun-Nyoung Yu, Sang-Hun Kim, Pann-Ghill Suh, Jae-Hoon Ji, Hak-Sun Yu, Yeong-Min Park and Soon-Cheol Ahn

Abstract
Previously, we reported that salinomycin induces apoptosis of human prostate cancer cells through accumulated reactive oxygen species and mitochondrial membrane depolarization. To extend our understanding for the genomewide expression pattern, we performed cDNA microarray analysis for gene expression profiles in prostate PC-3 cells treated with salinomycin. We found a couple of differences from gene expression profiles. First of them, cyclins and cyclin-dependent kinases were down-regulated, whereas cyclin dependent kinase inhibitors were upregulated, implicating inhibition of cell cycle progression. Second, HSPA5/Bip, DDIT3/CHOP, TRIB3, ATF4 and ATF6 regarding endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were increased at mRNA and protein levels, indicating salinomycin-induced growth inhibition of PC-3 cells seem to be mediated through induction of ER stress and activation of the UPR pathway. Our finding should be useful for understanding genomewide expression patterns of salinomycin-mediated cell cycle arrest and ER stress response toward induction of apoptosis and be helpful for finding future cancer therapeutic targets in prostate cancer cells.

исследовательская статья

ADAM33 as a New Biomarker for Invasive Lobular Breast Carcinoma

Abstract
Invasive ductal carcinoma (IDC) and invasive lobular breast carcinoma (ILC) are the most common malignancies compromising the breast tissue in women worldwide. ILCs tend to form metastasisin remote locations, such as the gastrointestinal tract, peritoneal surface and retroperitoneum, compared with IDCs that move preferentially to the lymph nodes, lung, pleura, liver, brain and bones. The histological characteristics of these two tumors are very similar and there is no useful molecular marker to differentiate IDC from ILC to date. In this study, we cloned and expressed ADAM33 recombinant protein cystein rich domain in order to produce polyclonal antibodies and used it as a new immnunohistochemical molecular biomarker that specifically recognizes the ILC breast cancer subtype.

исследовательская статья

Pharmacological Evaluation of Gatifloxacin in Chemically Induced Hepatocarcinogenesis: A New Tool for Hepatocellularcarcinoma Treatment

Muhammad Afzal, Imran Kazmi, Ruqaiyah Khan, Rajbala Singh, Mohammad Pravez, Faisal Imam and Firoz Anwar

Abstract
Introduction: Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide. In this study
Gatifloxacin an antimicrobial drug which has been banned due to some serious adverse effects evaluated for
the other pharmacological activities. Data from the present investigation suggest that Gatifloxacin suppresses the tumors and decrease the biochemical markers which are elevated in HCC.
Objective: This study is an attempt to evaluate the potential chemopreventive influence of Gatifloxacin in
hepatocarcinogenic rats. Hepatocarcinogeneis was induced by a single intraperitoneal injection of diethylnitrosamine (DENA) in phosphate buffer (200 mg/kg).
Results and conclusion: Experimental animals exposed to DENA caused a significant alteration in serum
indices of liver enzymes glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), acid phophatase (AP), total cholesterol (TC), triglycerides (TG) and high density lipoproteins (HDL), total proteins (TPR) and blood glucose level in tested animals. Results also revealed severe histological and immunohistochemical changes in hepatic tissues. These included disorganized hepatic parenchyma, appearance of pseudoacinar and trabecular arrays of hepatocytes and alterations in alpha fetoprotein (AFP) levels. Administration of Gatifloxacin relatively improved the biochemical parameters to values approximating those of the normal controls. SGOT, SGPT, ALP, level was significantly decreased (p<0.001, p<0.01, p<0.001 respectively) in therapeutic control while TPR, ALB level was significantly increased (p<0.001, p<0.001 respectively) and delayed the initiation of carcinogenesis. Rats treated with Gatifloxacin only showed altered levels of liver enzymes, arrhythmic symptoms and abdominal fat deposition. In conclusion, DENA significantly changes the biological enzymatic activities in serum and the integrity of hepatic tissues. Hence, Gatifloxacin proved to possess
the potential for the treatment of hepatocellularcarcinomas in rats exposed to DENA.

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