Biomedical subjects

M Hindi

Publications and source records attributed to M Hindi.

5 recordsLinked to original sources

PubMed2001

Melanoma differentiation associated gene-7 (mda-7): a novel anti-tumor gene for cancer gene therapy.

BACKGROUND: The mda-7 gene (melanoma differentiation associated gene-7) is a novel tumor suppressor gene. The anti-proliferative activity of MDA-7 has been previously reported. In this report, we analyze the anti-tumor efficacy of Ad-mda7 in a broad spectrum of cancer lines. MATERIALS AND METHODS: Ad-mda7-transduced cancer or normal cell lines were assayed for cell proliferation (tritiated thymidine incorporation assay, Alamar blue assay, and trypan-blue exclusion assay), apoptosis (TUNEL, and Annexin V staining visualized by fluorescent microscopy or FACs analysis), and cell cycle regulation (Propidium Iodide staining and FACs analysis). RESULTS: Ad-mda7 treatment of tumor cells resulted in growth inhibition and apoptosis in a temporal and dose-dependent manner. The anti-tumor effects were independent of the genomic status of p53, RB, p16, ras, bax, and caspase 3 in these cells. In addition, normal cell lines did not show inhibition of proliferation or apoptotic response to Ad-mda7. Moreover, Ad-mda7-transduced cancer cells secreted a soluble form of MDA-7 protein. Thus, Ad-mda7 may represent a novel gene-therapeutic agent for the treatment of a variety of cancers. CONCLUSIONS: The potent and selective killing activity of Ad-mda7 in cancer cells but not in normal cells makes this vector a potential candidate for cancer gene therapy.

Adenoviridae↗

PubMed2000

Genomic rearrangements of the APC tumor-suppressor gene in familial adenomatous polyposis.

Germline mutations of the adenomatous polyposis coli (APC) tumor-suppressor gene result in the hereditary colorectal cancer syndrome familial adenomatous polyposis (FAP). Almost all APC mutations that have been identified are single-nucleotide alterations, small insertions, or small deletions that would truncate the protein product of the gene. No well-characterized intragenic rearrangement of APC has been described, and the prevalence of this type of mutation in FAP patients is not clear. We screened 49 potential FAP families and identified 26 different germline APC mutations in 30 families. Four of these mutations were genomic rearrangements resulting from homologous and nonhomologous recombinations mediated by Alu elements. Two of these four rearrangements were complex, involving deletion and insertion of nucleotides. Of these four rearrangements, one resulted in the deletion of exons 11 and 12 and two others resulted in either complete or partial deletion of exon 14. The fourth rearrangement grossly altered the sequence within intron 14. Although this rearrangement did not affect any coding sequence of APC at the genomic DNA level, it caused inappropriate splicing of exon 14. These rearrangements were initially revealed by analyzing cDNAs and could not have been identified by using mutation detection methods that screened each exon individually. The identification of a rearrangement that did not alter any coding exons yet affected the splicing further underscores the importance of using cDNA for mutation analysis. The identification of four genomic rearrangements among 30 mutations suggests that genomic rearrangements are frequent germline APC mutations.

Adenomatous Polyposis Coli↗

PubMed1999

Technology evaluation: StealthVector (HIV) Enzo.

Efficient inhibition of human immunodeficiency virus-1 (HIV-1) replication with intracellularly expressed antiviral genes would be an important step toward clinical gene therapy for HIV-1 disease. Enzo Biochem is investigating and developing antisense genes as a potential gene therapy approach against a variety of conditions including acquired immunodeficiency syndrome (AIDS), cancer and hepatitis. The subsidiary of Enzo Biochem, Enzo Therapeutics, utilized its StealthVector technology and initiated phase I trials in July 1998 [291511,307156]. StealthVector, which is comprised of independent antisense sequences directed against two functional HIV-1 regions, is involved in regulation of gene expression soon after HIV infection, transactivation response (TAR) and tat/rev. StealthVector localizes primarily in the cell nucleus, where it could be most effective in inhibiting viral growth.

Biotechnology↗

PubMed1985

Ab interno retinochoroidectomy in primates.

Primates underwent the ab interno removal of up to a 6 X 7-disc diameter area of the retina and choroid adjacent to the optic disc. The area of resection was treated three weeks before surgery with an encircling row of xenon arc photocoagulation. Surgery involved photocoagulation of the entire resected area and removal of the retina and choroid using a wide-angle cutter vitrophage. Vitreous fluid was replaced in 50% of the eyes with sodium hyaluronate (Healon). The majority of eyes in which the vitrectomy fluid was replaced with saline solution became phthisical. All but one eye containing sodium hyaluronate recovered preoperative intraocular pressures and maintained the integrity of the remaining intraocular structures.

Animals↗

PubMed1985

Clearance of intravitreal 3H-fluorouracil.

The clearance of intravitreally administered 5-fluorouracil (5-FU) was studied under five experimental conditions. The same nontoxic dose resulted in similar initial intravitreal concentrations and cleared rapidly from all eyes (approximately 90% clearance within eight hours). Half-life values ranged from 46 to 168 minutes. The longest half-life occurred in aphakic-vitrectomized eyes in which hyaluronic acid (Healon) was substituted for vitreous (168 minutes). A similar half-life was found in normal eyes (150 minutes). The shortest half-life occurred in aphakic-vitrectomized eyes postoperatively (46 minutes). Intermediate half-life values occurred in vitrectomized but phakic eyes postoperatively (67 minutes) and in aphakic-vitrectomized "quiet" eyes (at least two weeks postoperatively) (82 minutes).

Animals↗