Wade P. Parks

Bio: Wade P. Parks is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Virus & RNA. The author has an hindex of 32, co-authored 55 publications receiving 5078 citations.

Studies on the Nucleic Acid Sequences of Kirsten Sarcoma Virus: a Model for Formation of a Mammalian RNA-Containing Sarcoma Virus

Abstract: The genetic information contained in the Kirsten and Moloney strains of mammalian RNA-containing sarcoma viruses has been analyzed by RNA · 3H-DNA hybridization. Kirsten sarcoma virus has been found to possess two distinct sets of nucleic acid sequences. One set of sequences is contained in murine type C helper virus, and the other set is contained in rat type C helper virus. Moloney sarcoma virus contains sequences of murine type C helper virus but not of rat type C helper virus. The results indicate that Kirsten sarcoma virus arose through a process of recombination between Kirsten murine leukemia virus and nucleic acid sequences found in rat cells. A model is suggested for the formation of transforming type C viruses involving the transduction of oncogenic information.

Harvey Sarcoma Virus: A Second Murine Type C Sarcoma Virus with Rat Genetic Information

Abstract: The nucleic acid sequences found in the Harvey strain of murine sarcoma virus have been analyzed by RNA[(3)H]DNA and [(3)H]RNADNA hybridization techniques The Harvey strain of murine sarcoma virus has been found to possess at least two sets of nucleic acid sequences One set of sequences is contained in the Moloney strain of mouse type-C virus, and the other set is contained in DNA transcripts synthesized in endogenous reactions containing rat type-C virus(es) The nucleic acid sequences that are detected in the Harvey sarcoma virus with the DNA probes synthesized from the rat type-C virus(es) are related to the rat sequences detected in the Kirsten strain of murine sarcoma virus The results support the model that both Kirsten and Harvey sarcoma viruses arose through a process of recombination or reassortment between mouse type-C viruses and sequences in rat cells and suggest that the information for transformation of fibroblasts may be contained in the rat type-C or cellular genome

Immunological Characterization of Primate C-Type Virus Reverse Transcriptases

Abstract: Antisera to the reverse transcriptase of C-type viruses provides a method for classifying the species of origin; the newly isolated primate C-type viruses are found to have reverse transcriptases which are immunologically distinguishable from those of C-type viruses of lower animals.

Radioimmunoassay of mammalian type C viral proteins. I. Species specific reactions of murine and feline viruses.

Abstract: A radioimmune precipitation assay (RIPA) for the major internal polypeptide of mammalian type C viruses is described. Gel chromatography and isoelectric focusing resulted in a polypeptide of approximately 30,000 daltons which migrated as a single band in three different dissociating systems as analyzed by polyacrylamide gel electrophoresis. This VP3(gs) protein from murine and feline type C viruses has species specific antigenic reactivities which were not altered by chemical iodination. 125 I-labeled VP3(gs) was a sensitive probe for antibodies. By employing limiting concentrations of antibody in RIPA, unlabeled murine or feline VP3(gs) antigen could be quantitated by competition with labeled polypeptide. This double antibody VP3(gs) antigen assay was at least 500 times more sensitive than complement-fixation or immunodiffusion and was specific for type C viruses of the homologous species.

Disruption of epithelial cell-matrix interactions induces apoptosis

Abstract: Cell-matrix interactions have major effects upon phenotypic features such as gene regulation, cytoskeletal structure, differentiation, and aspects of cell growth control. Programmed cell death (apoptosis) is crucial for maintaining appropriate cell number and tissue organization. It was therefore of interest to determine whether cell-matrix interactions affect apoptosis. The present report demonstrates that apoptosis was induced by disruption of the interactions between normal epithelial cells and extracellular matrix. We have termed this phenomenon "anoikis." Overexpression of bcl-2 protected cells against anoikis. Cellular sensitivity to anoikis was apparently regulated: (a) anoikis did not occur in normal fibroblasts; (b) it was abrogated in epithelial cells by transformation with v-Ha-ras, v-src, or treatment with phorbol ester; (c) sensitivity to anoikis was conferred upon HT1080 cells or v-Ha-ras-transformed MDCK cells by reverse-transformation with adenovirus E1a; (d) anoikis in MDCK cells was alleviated by the motility factor, scatter factor. The results suggest that the circumvention of anoikis accompanies the acquisition of anchorage independence or cell motility.

Feasibility of Drug Screening with Panels of Human Tumor Cell Lines Using a Microculture Tetrazolium Assay

Abstract: For the past 30 years strategies for the preclinical discovery and development of potential anticancer agents have been based largely upon the testing of agents in mice bearing transplantable leukemias and solid tumors derived from a limited number of murine as well as human sources. The feasibility of implementing an alternate approach, namely combined in vitro/in vivo screening for selective cytotoxicity among panels of human tumor cell lines derived from a broad spectrum of human solid tumors is under investigation. A group of 30 cell lines acquired from a variety of sources and representing 8 lung cancer pathologies as well as 76 cell lines representing 10 other categories of human cancer (carcinomas of colon, breast, kidney, prostate, ovary, head and neck; glioma; leukemia; melanoma; and sarcoma) have exhibited acceptable growth characteristics and suitable colorimetric profiles in a single, standard culture medium. Measurements of in vitro growth in microculture wells by cell-mediated reduction of tetrazolium showed excellent correlation (0.89 less than r2 less than 0.98) with measurements of cellular protein in adherent cell line cultures as well as viable cell count in suspension cell line cultures (0.94 less than r2 less than 0.99). Since the microculture tetrazolium assay provides sensitive and reproducible indices of growth as well as drug sensitivity in individual cell lines over the course of multiple passages and several months' cultivation, it appears suitable for initial-stage in vitro drug screening.

A Rapid in Vitro Assay for Quantitating the Invasive Potential of Tumor Cells

Abstract: We have reconstituted a matrix of basement membrane onto a filter in a Boyden chamber and assessed the ability of various malignant and nonmalignant cells to penetrate through the coated filter. Cells from all the malignant cell lines tested were able to cross the matrix in 5-6 h, whereas human fibroblasts as well as mouse 3T3 and 10T1/2 cell lines, which are not tumorigenic, were not invasive. In addition, normal primary prostate epithelial cells and benign prostatic hyperplasia cells were not invasive when tested in this assay, whereas malignant prostate carcinoma cells were highly invasive. Parallel experiments with these prostatic cells using the intrasplenic assay for metastasis detection in the nude mouse confirmed the benign behavior of the former cells and the metastatic phenotype of the latter ones. These results suggest that this in vitro test allows the rapid and quantitative assessment of invasiveness and a means to screen for drugs which alter the invasive phenotype of tumor cells.

RAS oncogenes: the first 30 years

Abstract: From the pioneering work with acute transforming retroviruses to the current post-genomic era, RAS genes have always been at the leading edge of signal transduction and molecular oncology. Yet, a complete understanding of RAS function and dysfunction - mainly in human cancer - is still to come. The knowledge that has accumulated since their discovery 30 years ago has, however, been remarkable, and should pave the way for not only solving the outstanding issues regarding RAS biology, but also for developing efficacious drugs that could have a significant impact on cancer treatment.