Talat Haqqi
Cleveland Clinic
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Featured researches published by Talat Haqqi.
The FASEB Journal | 1998
Seiji Kondo; Yoshikazu Tanaka; Yasuko Kondo; Masahiro Hitomi; Gene H. Barnett; Yukihito Ishizaka; Jinbo Liu; Talat Haqqi; Akiko Nishiyama; Bryant Villeponteau; John K. Cowell; Barbara P. Barna
Telomerase, the enzyme that elongates telomeric DNA (TTAGGG)n, may be involved in cellular immortality and oncogenesis. To investigate the effect of inhibition of telomerase on tumor cells, we transfected the antisense vector against the human telomerase RNA into human malignant glioma cells exhibiting telomerase activity. After 30 doublings, some subpopulations of transfectants expressed a high level of interleukin‐1β‐converting enzyme (ICE) protein and underwent apoptosis. In contrast, other subpopulations also showed enhanced ICE protein but escaped from apoptotic crisis and continued to grow, although their DNA synthesis, invasive ability, and tumorigenicity in nude mice were significantly reduced. Surviving cells demonstrated increased expression of glial fibrillary acidic protein and decreased motility, consistent with a more differentiated state. These cells also contained enhanced expression of the cyclin‐dependent kinase inhibitors (CDKIs) p21 and p27. Treatment of surviving nonapoptotic cells with antisense oligonucleotides against p27, but not p21, induced apoptotic cell death, suggesting that p27 may have protected differentiating glioma cells from apoptosis. These data show that treatment with antisense telomerase inhibits telomerase activity and subsequently induces either apoptosis or differentiation. Regulation of these two distinct pathways may be dependent on the expression of ICE or CDKIs.—Kondo, S., Tanaka, Y., Kondo, Y., Hitomi, M., Barnett, G. H., Ishizaka, Y., Liu, J., Haqqi, T., Nishiyama, A., Villeponteau, B., Cowell, J. K., Barna, B. P., Antisense telomerase treatment: induction of two distinct pathways, apoptosis and differentiation. FASEB J. 12, 801–811 (1998)
Oncogene | 1998
Yasuko Kondo; Seiji Kondo; Yoshikazu Tanaka; Talat Haqqi; Barbara P. Barna; John K. Cowell
Malignant glioblastomas grow very rapidly and are generally resistant to either DNA-damaging drugs or γ-irradiation. If tumor cells could be made more susceptible to cell death with treatments, this would clearly represent a significant improvement in the success of treatment. Recently, telomerase has become a focus of interest among oncologists as a target for treating cancer cells. Telomerase elongates telomeric DNA repeats (TTAGGG)n and is important in protecting and replicating DNA. The vast majority of tumor cells, indeed, express telomerase activity whereas normal somatic cells, except for a few cells, do not. Since telomerase is essential for protecting DNA, we may be able to make tumors more sensitive to treatments with DNA-damaging drugs by inhibiting telomerase activity. In this study, we used cis-diamminedichloroplatinum (cisplatin)-sensitive U87-MG cells and cisplatin-resistant U251-MG of human malignant glioblastoma cell lines. U87-MG cells did not express telomerase activity, whereas telomerase was highly detected in U251-MG cells. Interestingly, inhibition of telomerase with an antisense telomerase expression vector not only decreased telomerase activity but also increased susceptibility to cisplatin-induced apoptotic cell death in U251-MG cells. These findings suggest that treatment with antisense telomerase may represent a new chemosensitisation for tumors resistant to anticancer drugs.
Human Gene Therapy | 1998
Seiji Kondo; Yukihito Ishizaka; Takashi Okada; Yasuko Kondo; Masahiro Hitomi; Yoshikazu Tanaka; Talat Haqqi; Gene H. Barnett; Barbara P. Barna
Experimental Cell Research | 1997
Yasuko Kondo; Seiji Kondo; Jinbo Liu; Talat Haqqi; Gene H. Barnett; Barbara P. Barna
Ejc Supplements | 2008
Atreyi Dasgupta; Baisakhi Raychaudhuri; Talat Haqqi; Richard A. Prayson; Erwin G. Van Meir; Michael A. Vogelbaum; Saikh Jaharul Haque
Journal of Neurosurgery | 1998
Steven A. Toms; Aleck Hercbergs; Jinbo Liu; Seiji Kondo; Talat Haqqi; Graham Casey; Koichi Iwasaki; Gene H. Barnett; Barbara P. Barna
Cancer Research | 1998
Seiji Kondo; Yoshikazu Tanaka; Yasuko Kondo; Yukihito Ishizaka; Masahiro Hitomi; Talat Haqqi; Jinbo Liu; Gene H. Barnett; Emad S. Alnemri; Barbara P. Barna
Journal of Immunology | 1997
Jinbo Liu; W M Flanagan; Judith Drazba; M L Estes; Gene H. Barnett; Talat Haqqi; Seiji Kondo; Barbara P. Barna
Autoimmunity | 1995
Vincent K. Tuohy; Dawn Thomas; Talat Haqqi; Min Yu; Justin M. Johnson
Investigative Ophthalmology & Visual Science | 1998
Yasuko Kondo; Jinbo Liu; Talat Haqqi; Barbara P. Barna; Seiji Kondo