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Biomedical subjects

C W Boone

Publications and source records attributed to C W Boone.

At least 109 records · Page 6Linked to original sources
PubMed1982

Breast cancer skin test antigens of increased sensitivity prepared from vesicular stomatitis virus-infected tumor cells.

Crude membrane (CM) extracts were prepared from five cultured breast tumor lines (MDA-MB-157, MDA-MB-231, ZR75-1, HS0578T, and MCF-7) which had been infected with vesicular stomatitis virus (VSV) to augment their antigenicity. In skin test trials, CM extracts of uninfected MCF-7 cells elicited positive response in 0 of 13 (0%) tests in breast cancer patients, while VSV-MCF-7 elicited positive responses in 11 of the same 13 patients (84.6%). CM extracts of VSV-ZR75-1 and VSV-MCF-7 elicited greater delayed hypersensitivity responses (mm induration at 48 hr) in breast cancer patients than in patients with lung carcinoma or melanoma. Although the sensitivity of VSV-ZR75-1 was too low (ten of 28, or 35.7% of tests positive) to be useful as a skin test antigen, VSV-MCF-7 elicited positive responses in 30 of 38 (78.9%) tests in breast cancer patients, as compared to two of 15 (13.3%) and two of 13 (15.4%) of tests in patients with lung carcinoma and melanoma, respectively. The "virus-augmented" CM extract of cultured MCF-7 cells exhibited markedly greater sensitivity as compared to control MCF-7 extracts (P less than .005), with a high degree of specificity for breast cancer patients as compared to patients with the other neoplasms (P less than .00001). The results of skin testing with VSV-MCF-7 CM extracts demonstrated antigenic cross-reactivity with a large number of breast cancer patients, a finding of great importance for any potential immunotherapy and/or immunodiagnosis.

Adult↗
PubMed1982

Anticancer drugs: effect on the cloning of Raji lymphoma cells in soft agar.

The effect of 11 anticancer drugs on the ability of Raji lymphoma cells to form colonies in soft agar was determined with the use of both a 1-hour and a continuous drug exposure. Three distinct patterns of drug sensitivities were observed: a) Dactinomycin, adriamycin, bleomycin, mitomycin C, vincristine, and cis-platinum II all produced a dose-dependent reduction in colony formation following a 1-hour exposure, which was further augmented by a continuous exposure to the drugs; b) the antimetabolites (methotrexate, beta-cytosine arabinoside, and 5-fluorouracil) and pentamethylmelamine had no suppressive effects on colony formation with a 1-hour exposure, but they produced marked cytotoxicity with continuous drug exposure; and c) L-phenylalanine mustard had the same degree of colony suppression with both a 1-hour and a continuous drug exposure. Preincubation of Raji cells with an enzyme mixture (DNase + pronase + collagenase) did not alter the degree of colony suppression observed with the anticancer drugs. These results indicate that continuous drug exposure should be compared to a 1-hour drug incubation to determine in vitro drug sensitivities of fresh human tumors in the soft agar clonogenic assay, because the 1-hour drug exposure may not identify certain drugs that are potentially clinically active.

Agar↗
PubMed1981

PRomotion of smooth surface tumorigenicity by phorbol myristate acetate in Balb/3T3 cells and Balb/3T3 T proadipocytes.

In vitro exposure of Balb/3T3 cells to phorbol and phorbol myristate acetate significantly increased their tumorigenic potential when implanted sc on smooth surface plates into syngeneic mice. This finding supports the hypothesis that many so-called normal cell lines may actually represent initiated cells that can be induced to become tumorigenic following exposure to promoting agents. Since the tumorigenic potential of many tissues in vivo is inversely proportional to the state of differentiation of the stem cell populations undergoing transformation, we assayed the relative tumorigenicity of Balb/3T3 T proadipocytes, which can differentiate in culture, and Balb/3T3 cells, which cannot differentiate in culture. The effects of tumor-promoting agents on these cells were also tested. Plate-implanted Balb/3T3 T proadipocytes were markedly less tumorigenic than Balb/3T3 cells, and Balb/3T3 T proadipocytes were not sensitive to the promotional effects of phorbol myristate acetate.

Animals↗
PubMed1980

The plate-implant as a bioassay for the neoplastic potential of cultured cells.

One objective of this study was to test the plate implant as an in vivo bioassay for the neoplastic state with pairs of cell lines that were non-tumorigenic and tumorigenic when inoculated in suspension at various sites. Each pair originated from a common cell pool or from one cell derived from normal rat or mouse embryonic tissue. The implantation of cells attached to polycarbonate plates was compared with the subcutaneous injection of comparable numbers of cells in suspension or the intraocular injection of 10(5) cells. In addition, some implants of glass helices with attached cells were made into syngeneic mice and compared with injection of comparable cell numbers intramuscularly into X-irradiated hosts. A total of 10 lines or clones were tested on plates. Of four lines that were non-tumorigenic when inoculated in suspension either subcutaneously or intraocularly, two were tumorigenic when implanted subcutaneously attached to plastic plates. The remaining two are the first permanent rodent lines that have not been tumorigc on plastic plates. Of the remaining six lines, all were tumorigenic on plates and two produced sarcomas at a higher frequency on plates than in suspension. Cytologic diagnoses of the cells implanted on plates, subcutaneously and intraocularly, correlated best with the results from plate implants. Of three mouse lines implanted on helices, two were equally tumorigenic in suspension and on helices, whereas the third was tumorigenic on helices only. The plate implant was more satisfactory technically than the helices and proved to be one of the most sensitive bioassays for the neoplastic state of cultured cells.

Animals↗
PubMed1980

Plate-induced tumors of BALB/3T3 cells exhibiting foci of differentiation into pericytes, chondrocytes, and fibroblasts.

The BALB/3T3 clone A31 mouse embryo cell line has been used by many investigators as a model "normal" "fibroblast" line for a variety in vitro studies. It has been shown, however, that these cells are not "normal" because they will produce tumors within 2-4 months if 3 x 10(4) cells are implanted subcutaneously in BALB/c mice attached to 0.2 x 5 x 10-mm plastic plates. Previous studies also suggested that these cells were not fibroblasts because they gave rise tumors with the characteristics of vascular endothelium not fibroblasts. We now report that BALB/3T3 (clone A31), BALB/3T3-T, a proadipocyte subclone of clone A31 cells, and six recent subclones of BALB/3T3-T cells show additional differentiation patterns were tumors derived by implantation of these cells attached to plastic plates are examined. Differentiation into pericytes, chondrocytes, and fibroblasts was observed. We conclude that the BALB/3T3 clone A31 cell line and related lines are multipotent mesenchymal cells which are capable of differentiation into a variety of cell types.

Adipose Tissue↗
PubMed1979

"Sontaneous" neoplastic transformation in vitro: a form of foreign body (smooth surface) tumorigenesis.

Explants of subcutaneous connective tissue from adult BALB/c mice into plastic petri dishes were serially subcultured and tested for tumorigenicity in two ways: by the subcutaneous implantation of cells attached to plastic plates (1 by 5 by 10 millimeters), and by the subcutaneous injection of cells suspended in saline. Cells grown in vitro for 18 or more days before being implanted attached to a plastic plate (2.4 x 10(4) to 3.4 x 10(5) cells per plate) formed tumors after 24 to 79 weeks. The latent period before tumor appearance correlated inversely with the time spent by the cells in tissue culture. Cells inoculated in saline suspension (10 to 100 times the above number per plate) did not form tumors until after 84 days in vitro; plates alone did not induce tumor formation within more than 1 1/2 years of implantation. The tumors arising from the plate-attached cells were transplantable without plates and histologically appeared to be undifferentiated sarcomas. It is well established that smooth-surfaced foreign bodies, regardless of their chemical composition, will produce sarcomas when transplanted subcutaneously in rodents. We interpret our data, particularly the decrease in tumor latent period with time spent in tissue culture, as indicating that a smooth surface was acting as a carcinogen first in vitro (the surface of the tissue culture dish) and then in vivo (the surface of the plastic plate).

Animals↗
PubMed1979

Temperature-dependent alteration in immunogenicity of tumor-associated transplantation antigen monitored via paraformaldehyde fixation.

Paraformaldehyde-fixed mKSA tumor cells of BALB/c mice were shown to retain tumor-associated transplantation antigen (TATA) activity to a degree comparable to that of X-ray-inactivated tumor cells under the optimal conditions of 1% paraformaldehyde for 30 min at 37 degrees. Unexpectedly, the TATA activity of cells fixed below 10 degrees was greatly reduced. This temperature effect was reversible. TATA activity was restored if the cells were returned to 37 degrees before fixation. Fixation at all temperatures for longer than 2 hr or at paraformaldehyde concentrations greater than 1% also caused a decrease in immunogenicity. Spleen cells from mice immunized with tumor cells fixed at 37 degrees were able to more effectively neutralize tumor growth in the Winn assay compared with those from mice immunized with cells fixed at 0 degrees. Immunization with paraformaldehyde-fixed tumor cells was completely specific. Mice immunized with an antigenically unrelated tumor were not rendered immune to tumor challenge. Fixed tumor cells could be stored for at least 1 month without loss of TATA activity.

Animals↗
PubMed1978

Immunological study of two stocks of Moloney sarcoma virus producing regressor and progressor tumors in C57BL/6 mice.

The immune response to progressor murine sarcoma virus (P-MuSV)2 and regressor murine sarcoma virus (R-MuSV) was analyzed by the radioisotopic footpad assay (FPA) for delayed hypersensitivity (DH) and by the membrane immunofluorescence assay for anti-tumor antibodies. In mice injected with P-MuSV, the footpad response remained at a low level for 7 weeks, while membrane immunofluorescence antibody titers reached their maximum levels after 5 weeks. By contrast, in mice injected with R-MuSV, the footpad response rose to a maximum by 4 weeks and membrane immunofluorescence antibody titers reached a maximum after 4 weeks. The adoptive footpad response reached its highest level in 2 weeks. A most striking difference between the P-MuSV and the R-MuSV systems was the lower immunogenicity of tumor cells induced by the P-MuSV as measured by the FPA. Considerable differences between the two stocks were also observed in oncogenic activity and tumor growth patterns. The P-MuSV contained one-tenth the amount of helper Moloney leukemia virus found in R-MuSV. Addition of more helper Moloney leukemia virus to the P-MuSV did not produce regressor tumors.

Animals↗
PubMed1978

Melanoma skin test antigens of improved sensitivity prepared from vesicular stomatitis virus-infected tumor cells.

Crude membrane (CM) extracts from three different cultured human melanoma lines that were "virus-augmented" (infected with vesicular stomatitis virus (VSV) and subsequently inactivated by ultraviolet light) produced positive skin tests in 17 of 20 (85%), 11 of 20 (55%), and 13 of 18 (72%) tests, respectively, performed in 20 melanoma patients. Identical CM extracts from the same melanoma lines that had not been infected with VSV gave positive skin tests in 2 of 20 (10%), 4 of 20 (20%), and 2 of 18 (11%) tests, respectively, performed in the 20 melanoma patients, and no positive tests in the control patients. The 3 virus-augmented extracts were positive in only 2 of 18 (11%), 0 of 18 (0%), and 1 of 17 (6%) control subjects, respectively. The controls consisted of six normal volunteers and 12 patients with cancers other than melanoma. The "virus-augmented" CM extracts thus exhibited markedly greater sensitivity without significant loss of specificity as compared to nonvirus augmented extracts when used as tumor-specific melaonma skin test antigens.

Adult↗
PubMed1978

Neoplasms produced from C3H/10T 1/2 cells attached to plastic plates; saturation density, anchorage dependence and serum requirement of in vitro lines correlated with growth aggressiveness in vivo.

The C3H/10T 1/2 embryo cell line, which is nontumorigenic when inoculated subcutaneously in saline suspension, produces tumors when implanted subcutaneously attached to 1 X 5 X 10 mm plastic plates. Under these in vivo conditions there is direct selection for "spontaneous" transformants that have undergone the specific cellular alterations required for neoplastic behavior. This is in contrast to the conventional situation where transformants are obtained in vitro and are only secondarily tested in vivo for neoplastic behavior. Early passages of cell lines from four different C3H/10T 1/2 tumors explanted back in culture were quantitatively examined for tumorigenicity and for alteration in the properties of density inhibition, anchorage dependence, serum requirement, and plasminogen activator production. A fairly consistent quantitative relationship was found between the degree of growth aggressiveness in vivo and the degree of expression of these phenotypic markers of the transformed state in vitro during early passages of the cell lines after tumor explantation.

Animals↗
PubMed1978

Augmented immunogenicity of tumor cell membranes produced by infection with influenza virus as compared to Moloney sarcoma virus.

The tumor-associated transplantation antigens (TATA) of crude membrane extracts from SV40-transformed BALB/3T3 tumor cells lytically infected with influenza virus were markedly more immunogenic than were extracts from uninfected cells measured either by the ability to induce heightened resistance to tumorgraft challenge or by heightened lymphocyte-mediated cytotoxicity against tumor cells in vitro. When intact tumor cells (as opposed to membrane extracts) were productively infected with Moloney sarcoma virus, they were made so immunogenic that they would only grow in X-irradiated syngeneic animals. Yet crude membrane extracts from the Moloney sarcoma virus-infected tumor cells showed no increase in TATA activity analogous to that seen after infection with influenza virus. Thus, influenza virus augmentation of tumor membrane TATA may operate by a different mechanism than does the oncornavirus augmentation of intact tumor cell TATA reported by others. It appears that Moloney sarcoma virus and possibly other oncornaviruses cannot be used to augment the TATA activity of tumor cell membranes in the same way that other surface-budding viruses can.

Animals↗