Browsing by Author "Bharali, Dhruba Jyoti"
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Item Response of human pancreatic cancer cell xenografts to tetraiodothyroacetic acid nanoparticles(Springer, 2013-06) Lin, Hungyung; Sudha, Thangirala; Bharali, Dhruba Jyoti; Meng, Ran; Tang, Hengyuan; Davis, Faith B.; Stain, Steven Charles; Davis, Paul J.; Mousa, Shaker A.; Yalçın, Murat; Uludağ Üniversitesi/Veteriner Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0002-5600-8162; AAG-6956-2021; 57192959734Tetraiodothyroacetic acid (tetrac) and its nanoparticle formulation (Tetrac NP) act at an integrin cell surface receptor to inhibit tumor cell proliferation and tumor-related angiogenesis. Human pancreatic cancer cell (PANC-1 and MPanc96) xenografts were established in nude mice, and the effects of tetrac versus Tetrac NP on tumor growth and tumor angiogenesis were determined. The in vitro effects of tetrac and Tetrac NP were also determined by reverse transcription polymerase chain reaction or immunoblot on gene expression or gene products relevant to cell cycle arrest, apoptosis, or angiogenesis. Tetrac and Tetrac NP reduced both PANC-1 tumor mass by 45-55 % and PANC-1 tumor hemoglobin content, a marker of angiogenesis, by 50-60 % (*P < 0.05) in treated groups vs. controls by treatment day 15. Comparable results were obtained with tetrac and Tetrac NP in suppressing tumor growth and tumor angiogenesis in MPanc96 xenografts. In vitro studies showed that tetrac and Tetrac NP caused accumulation of pro-apoptotic protein BcLx-s. Tetrac NP was more effective than tetrac in increasing cellular abundance of mRNAs of pro-apoptotic p53 and p21 and anti-angiogenesis thrombospondin 1 protein in PANC-1 and MPanc96 cancer cell lines. Tetrac NP noticeably decreased expression of EGFR and of anti-apoptosis gene XIAP; tetrac did not affect EGFR and increased XIAP mRNA in both MPanc96 and PANC-1. In conclusion, tetrac or Tetrac NP effectively inhibited human pancreatic xenograft growth and tumor angiogenesis via a plasma membrane receptor that downstream modulated cellular abundance of proteins or mRNAs relevant to apoptosis and angiogenesis.Item Tetraiodothyroacetic acid (Tetrac) and nanoparticulate tetrac arrest growth of medullary carcinoma of the thyroid(Endocrine, 2010-04) Dyskin, Evgeny; Lansing, Lawrence S.; Bharali, Dhruba Jyoti; Mousa, Shaymaa S.; Bridoux, Alexandre; Hercbergs, Aleck A.; Lin, Hungyung; Davis, Faith B.; Glinsky, Gennadi Victor; Glinskii, Anna B.; Ma, J.; Davis, Paul J.; Mousa, S. A.; Yalçın, Murat; Uludağ Üniversitesi/Veterinerlik Fakültesi/Temel Bilimler Bölümü.; 0000-0002-5600-8162; AAG-6956-2021; 57192959734Context: Tetraiodothyroacetic acid (tetrac) blocks angiogenic and tumor cell proliferation actions of thyroid hormone initiated at the cell surface hormone receptor on integrin alpha v beta 3. Tetrac also inhibits angiogenesis initiated by vascular endothelial growth factor and basic fibroblast growth factor. Objective: We tested antiangiogenic and antiproliferative efficacy of tetrac and tetrac nanoparticles (tetrac NP) against human medullary thyroid carcinoma (h-MTC) implants in the chick chorioallantoic membrane (CAM) and h-MTC xenografts in the nude mouse. Design: h-MTCcells were implanted in the CAM model (n = 8 per group); effects of tetrac and tetrac NP at 1 mu g/CAM were determined on tumor angiogenesis and tumor growth after 8 d. h-MTC cells were also implanted sc in nude mice (n = 6 animals per group), and actions on established tumor growth of unmodified tetrac and tetrac NP ip were determined. Results: In the CAM, tetrac and tetrac NP inhibited tumor growth and tumor-associated angiogenesis. In the nude mouse xenograft model, established 450-500 mm(3) h-MTC tumors were reduced in size over 21 d by both tetrac formulations to less than the initial cell mass (100 mm(3)). Tumor tissue hemoglobin content of xenografts decreased by 66% over the course of administration of each drug. RNA microarray and quantitative real-time PCR of tumor cell mRNAs revealed that both tetrac formulations significantly induced antiangiogenic thrombospondin 1 and apoptosis activator gene expression. Conclusions: Acting via a cell surface receptor, tetrac and tetrac NP inhibit growth of h-MTC cells and associated angiogenesis in CAM and mouse xenograft models.