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Biomedical subjects

P Pechan

Publications and source records attributed to P Pechan.

8 recordsLinked to original sources
PubMed1999

Intraarterial delivery of adenovirus vectors and liposome-DNA complexes to experimental brain neoplasms.

This study investigated the intraarterial delivery of genetically engineered replication-deficient adenovirus vectors (AVs) and cationic liposome-plasmid DNA complexes (lipoDNA) to experimental brain tumors. Adenovirus or lipoDNA was injected into the internal carotid artery (ICA) of F344 rats harboring intracerebral 9L gliosarcomas, using bradykinin (BK) to selectively permeabilize the blood-tumor barrier (BTB). Brain and internal organs of the animals were collected 48 hr after vector injection and stained for expression of the marker gene product, beta-galactosidase (beta-Gal). Intracarotid delivery of AV to 9L rat gliosarcoma without BTB disruption resulted in transgene expression in 3-10% of tumor cells distributed throughout the tumor. Virus-mediated expression of beta-gal gene products in this tumor model was particularly high in small foci (< or = 0.5 mm), which had invaded the normal brain tissue surrounding the main tumor mass. In these foci more than 50% of tumor cells were transduced. BK infusion increased the amount of transgene-expressing cells in larger tumor foci to 15-30%. In the brain parenchyma only a few endothelial cells expressed beta-gal owing to AV-mediated gene transfer. Intracarotid delivery of lipoDNA bearing a cytoplasmic expression cassette rendered more than 30% of the tumor cells positive for the marker gene without BTB disruption. The pattern of distribution was in general homogeneous throughout the tumor. BK infusion was able to increase further the number of transduced tumor cells to more than 50%. Although lipoDNA-mediated gene transfer showed increased efficacy as compared with AV-mediated gene transfer, it had less specificity since a larger number of endothelial and glial cells also expressed the transgene. AV and lipoDNA injections, in the absence and presence of BK, also resulted in transduction of peripheral organs. AV showed its known predilection for liver and lung. In the case of lipoDNA, parenchymal organs such as liver, lung, testes, lymphatic nodes, and especially spleen, were transduced. These findings indicate that intracarotid application of AV and lipoDNA vectors can effectively transduce tumor cells in the brain, and that BTB modulation by BK infusion can further increase the number of transgene-expressing tumor cells.

Adenoviridae↗
PubMed1998

Targeting gene therapy vectors to CNS malignancies.

Gene therapy offers significant advantages to the field of oncology with the addition of specifically and uniquely engineered mechanisms of halting malignant proliferation through cytotoxicity or reproductive arrest. To confer a true benefit to the therapeutic ratio (the relative toxicity to tumor compared to normal tissue) a vector or the transgene it carries must selectively affect or access tumor cells. Beyond the selective toxicities of many transgene products, which frequently parallel that of contemporary chemotherapeutic agents, lies the potential utility of targeting the vector. This review presents an overview of current and potential methods for designing vectors targeted to CNS malignancies through selective delivery, cell entry, transport or transcriptional regulation. The topic of delivery encompasses physical and pharmaceutic means of increasing the relative exposure of tumors to vector. Cell entry based methodologies are founded on increasing relative uptake of vector through the chemical or recombinant addition of ligand and antibody domains which selectively bind receptors expressed on target cells. Targeted transport involves the potential for using cells to selectively carry vectors or transgenes into tumors. Finally, promoter and enhancer systems are discussed which have potential for selectivity activating transcription to produce targeted transgene expression or vector propagation.

Central Nervous System Neoplasms↗
PubMed1991

Bkm satellite DNA and ZFY in the coral reef fish Anthias squamipinnis.

We studied DNA from the protogynous sex-changing fish Anthias squamipinnis to evaluate the recent observation that male-specific bands are identified after hybridization with Bkm, a probe originating in the W chromosome of the snake Bungarus fasciatus. Sex-specific hybridization would imply modification of DNA structure during the sex-changing process. No sex-specific Bkm fragments were identified in our study, after digestion of DNA from 15 males and 11 adult females, despite the use of 12 different restriction enzymes. However, hybridization with Bkm did produce a distinct fingerprint pattern, similar to the fingerprint patterns described for other species after hybridization with GATA (GACA) type probes. In other experiments, the pDP1007 probe, which identifies the ZFY gene in the male-determining region of the human Y chromosome, generated identical hybridization patterns in DNA from males and females of A. squamipinnis and estimation of DNA mass by flow cytometry revealed identical genome sizes.

Animals↗
PubMed1986

Increased H-Y antigen levels associated with behaviorally induced, female-to-male sex reversal in a coral-reef fish.

It has been proposed that H-Y antigen is the synthetic product of sex-determining genes, and that H-Y antigen controls ontogenetic differentiation of the heterogametic sex throughout vertebrates. The coral-reef fish Anthias squamipinnis is a protogynous hermaphrodite in which all individuals mature initially as females. Males result when adult females change sex as a consequence of alterations in behavioral interactions within social groups. Three assay methods were used to measure H-Y antigen levels in the spleens, gonads, and epidermal tissue of 16 adult females and in 16 males that had been induced to change sex from a prior female phase by the removal of a pre-existing male from each of 16 social groups. In 15 male-female pairs, the H-Y antigen levels were higher in male than in female spleen, gonad, and epidermis tissues. The precise temporal relationship between the onset of sex change and the increase in the H-Y antigen level was not examined. If, as we strongly suspect, the temporal relationship proves to be close, the inference will be that the behavioral cues inducing sex change also influence the synthetic activity of genes controlling H-Y antigen production.

Animals↗
PubMed1985

Anti-male (anti-H-Y) male treatment influences progeny sex ratio.

Published data on progeny sex ratio changes resulting from induction or administration of anti-male antibody in parental generation were compared by Fisher's independent test of significance. Sex ratio (males/total) depression is highly significant (P less than 0.001). Our large sample size data confirm this result; significant progeny sex ratio decrease follows active anti-H-Y maternal immunization in mice or passive immunization in D. melanogaster.

Animals↗
PubMed1980

H-Y evolution.

The female:male sex ratio in litters born to C57 black mice immunized with male spleen preparations is 2:1 and males were stillborn. In addition Drosophila busckii males are H-Y antigen positive. It is argued that H-Y is the primary testicular determinant and that this role is evolutionarily ancient.

Animals↗
PubMed1979

H-Y antigen in the teleost.

H-Y antigen, presumably the product of mammalian testis-determining genes, has been detected in three species of teleost fish, Xiphophorus maculatus. Haplochromis burtoni, and Oryzias latipes, and in hybrids of the genus Tilapia. In X. maculatus H-Y was most readily detected in YY males, suggesting that a genetic determinant of H-Y antigen expression may exist on the teleost Y-chromosome. Although H-Y was detected in males and not in feamles in each of the species that we studied, male heterogamety has not been firmly established for H. burtoni. Thus despite the extreme phlyogenetic conservation of H-Y genes and their association with the Y-chromosome, it remains open to question whether H-Y will always be found in the heterogametic sex, and whether serologically defined H-Y antigen plays any part in the differentiation of the teleost gonad.

Animals↗