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Biomedical subjects

P Calabresi

Publications and source records attributed to P Calabresi.

At least 271 records · Page 15Linked to original sources
PubMed1979

N,N-dimethylformamide-induced alteration of cell culture characteristics and loss of tumorigenicity in cultured human colon carcinoma cells.

Human colon carcinoma cell lines established in this laboratory were treated in vitro with N,N-dimethylformamide. This polar solvent caused morphological changes in the cells as well as alterations in their growth properties. Untreated cells had cloning efficiencies of up to 77% in soft agar; treatment with N,N-dimethylformamide resulted in a complete loss of clonogenicity in semisolid medium. Growth in the presence of the polar solvent also effected a marked reduction in the tumorigenicity of the cells. Ten of ten nude mice that received a s.c. inoculum of 1 X 10(6) untreated cells developed tumors histologically similar to colonic adenocarcinomas in 10 to 14 days, whereas nine of ten nude mice inoculated with 1 X 10(6) treated cells have shown no sign of tumor 3 to 6 months postinjection. Removal of the polar solvent from the culture medium was accompanied by the reappearance of tumorigenicity and the original cell culture characteristics. Therefore, it appears that N,N-dimethylformamide can reversibly effect the reversion of cultured human colon carcinoma cells to less malignant cell types.

Animals↗
PubMed1978

Psoriasis and occlusive vascular disease.

To test the hypothesis that psoriasis is associated with an increased incidence of occlusive vascular disease (thrombophlebitis, myocardial infarction, pulmonary embolization, and cerebrovascular accident), the clinical records of 323 psoriatic and 325 non-psoriatic patients admitted to the dermatology service of the Roger Williams General Hospital were examined. The data obtained in this study suggest that (1) the occurrence rate of occlusive vascular disease is significantly greater in the psoriatic than in the non-psoriatic dermatological patient. This is particularly true in the male population; (2) psoriasis predisposes to occlusive vascular disease; and (3) the psoriatic patient with certain predisposing factors is at greater risk of experiencing an occlusive vascular episode than both the non-predisposed psoriatic and the non-psoriatic dermatological patient.

Age Factors↗
PubMed1978

Heterogeneity in drug sensitivity among tumor cell subpopulations of a single mammary tumor.

Three distinct subpopulations of tumor cells derived from a single parent strain BALB/cfC3H mammary adenocarcinoma were tested in vivo for sensitivity to cyclophosphamide, methotrexate, and 5-fluorouracil. Treatment was begun either 2 days after s.c. tumor cell injection or at the time when the tumors became palpable. It was given on a weekly basis for 4 weeks. The mice were observed for growth of the primary implant and for development of spontaneous metastases. The three subpopulations differed markedly in their sensitivity to the drugs. The effects of the drugs ranged from induction of regression of the "primary" to enhancement of metastases. The effect on primary growth was independent of that on metastasis. The effect of the time of administration of the drugs also varied among the subpopulations. The sublines were also tested in vitro with methotrexate and 5-fluorouracil. Again there were marked differences in sensitivity to inhibition of cell division by the drugs. The relative sensitivities in vitro did not correlate with observations in vivo. The existence of subpopulations of tumor cells, differing in sensitivity to therapeutic agents, within a single neoplasm, presents a challenge to development of assays capable of predicting drug response and to the selection of combination therapies.

Adenocarcinoma↗
PubMed1977

Ultrastructure of myeloma cells in a case with crystalcryoglobulinemia.

The bone marrow of a patient with multiple myeloma of the IgG2 Kappa type with spontaneously crystallizing cryoglobulin was studied by electron microscopy. The ultrastructure of the myeloma cells disclosed the presence of a crystalline material in the cytoplasm within the rough endoplasmic reticulum (RER) as well as in extracisternal sites. The crystalline material was also seen extracellulary with a distinctly unique subunit structure. The tubular units measured 200 +/- A (SEM) externally with an internal diameter of 100 +/- A (SEM). The intracellular distribution did not indicate a characteristic organelle association usually observed in protein synthesizing cells. It is suggested, based on the present observations and the findings of others, that the crystalline material may represent polymerized protein synthesized by free ribosomes mostly in extracisternal locations, a pattern often seen in neoplastic plasma cells. Diffusion to extracisternal sites of precrystalline material through the membranes of the RER is a possible alternative mechanism.

Bone Marrow↗
PubMed1977

Chemotherapy of cell-line-derived human colon carcinomas in mice immunosuppressed with antithymocyte serum.

An in vivo model is described for assessing the antitumor activity of chemotherapeutic agents. Tumors derived from human colon carcinoma cell lines injected into antithymocyte serum (ATS) immunosuppressed mice were used. In this system, both antitumor effects and host toxicity can be quantitated, permitting calculation of a Therapeutic Index. Compared with other xenograft models, the present system is simple, experiments are completed in less than 2 weeks, and the use of cultured cell lines allows in vitro studies to be performed. The in vitro sensitivities of one colon cell line to 22 chemotherapeutic agents and of four cell lines to three agents is reported. Four drugs used in treating colon cancer (Mitomycin C, 5-FU, BCNU, and methyl-CCNU) show antitumor activity in vivo in this system. Each has a low therapeutic index. Further work with this model is indicated, with the goal of finding new drugs with high Therapeutic Indices.

Animals↗
PubMed1977

Effect of sequence of administration of methotrexate, leucovorin, and 5-fluorouracil on mammary tumor growth and survival in syngeneic C3H mice.

The administration of methotrexate (1mg/kg), leucovorin (1 mg/kg), and (after a 1-hr interval) 5-fluorouracil (50 mg/kg) selectively suppresses antibody production in C3H mice without inhibiting, but even stimulating, cell-mediated immunity. The effect of this regimen, given at weekly intervals, was tested on the growth of recently arising syngeneic C3H/HeJ mammary tumors. Inhibition of growth was found in three types of experiments: (a) when treatment was begun 2 days after tumor implantation, (b) when it was begun 3 weeks after implantation, and (c) when it was begun after surgical enucleation of the tumor. The extent of the effect varied from tumor to tumor, but in all cases tumor incidence or growth was significantly inhibited. Comparison was made between the above regimen and two other sequences of administration of the same drugs, which are only weakly immunosuppressive of antibody production and which do not stimulate cell-mediated immunity. Survival of tumor-bearing mice was greater with the administration of methotrexate, then leucovorin, followed by 5-fluorouracil, than it was with the other two administration schedules.

Animals↗
PubMed1976

Stimulatory effects of 5-lodo-2'-deoxyuridine on number and function of splenic B- and T-cells and of macrophages in C3HeB/FeJ mice.

5-lodo-2'-deoxyuridine (lUdR) significantly increases the total number of spleen cells on the fourth day after administration of 100 mg/kg in normal C3HeB/FeJ male mice. The number of splenic B-cells [cells sensitive to the cytotoxic activity of a rabbit antiserum to mouse F(ab)2, plus complement] increases on the same day. The number of T-cells (cells sensitive to the cytotoxic activity of a rabbit antiserum to mouse brain-associated theta antigen, plus complement) and of macrophages (adherent-phagocytic cells) does not increase. Spleen cells from lUdR-treated mice show heightened responsiveness in vitro to Escherichia coli lipopolysaccharide or concanavalin A on Day 4 and Days 5 to 6, respectively. The rate of clearance of i.v.-injected colloidal carbon is also increased for 3 days after lUdR. Thus, lUdR is able to functionally activate either T- or B-cells or macrophages, but only to increase the number of splenic B-cells.

Animals↗
PubMed1975

Evaluation of cell-mediated reactivity and serum blocking factors in melanoma patients on chemotherapy.

Sequential assays for cell-mediated reactivity (CMR) and serum blocking factor (SBF) were performed in a group of 12 melanoma patients who were treated with one or both of the clinically available imidazole carboxamide derivatives, DTIC and TIC Mustard, in order to consider the effects of treatment and changing patterns of disease on the results of in vitro tests in individual patients. Microcytotoxicity assays and the dilute agar colony inhibition test were employed. Of the 12 patients, 8 had no change in CMR and 5 had no change in SBF. Three patients demonstrated a fall in both CMR and SBF to nondetectable levels, and 3 additional patients showed a fall in SBF only. From these results, we conclude that there is no significant depression of CMR in melanoma patients by either of the imidazole carboxamide derivatives used. The results of SBF are less conclusive and more open to question, since it is just a likely that any depression to undetectable levels may be due to a change in disease status rather than to coincident drug use. It appears that microcytotoxicity assay results on individual patients may be fortuitous and difficult to interpret, even though results seen in patients as a group indicate important trends. The microcytotoxicity assay is a useful tool for the experimental tumor immunologist, but its clinical usefulness in individual patients is limited.

Adult↗
PubMed1975

Stimulation of hemolysin plaque-forming cells by idoxuridine.

5-Iodo-2'-deoxyuridine markedly stimulates the production of hemolysin plaque-forming cells (HPFC) to sheep red blood cells in C3HeB/FeJ and A/J male and female mice. The degree of stimulation is dose dependent over a range of 50 to 200 mg/kg. Stimulation is observed when drug is given on the day of antigen administration, or up to 3 days thereafter, but not when given before antigen administration or 4 days thereafter. The stimulatory effect of IUdR given on day 2 after antigen is still noted on Day 15, but the time of HPFC production is not prolonged beyond that in controls. Both 19S and 7S HPFC are increased, although the effect on the latter is less pronounced. In addition to stimulating production of HPFC in immunized animals, 5-iodo-2'-deoxyuridine increases background HPFC production in nonimmunized mice by 250% when assayed on the day after treatment.

Animals↗
PubMed1975

Problems in the clinical use of the microcytotoxicity assay for measuring cell-mediated immunity to tumor cells.

Lymphocytes from control donors and from cancer patients have been tested for antitumor, cell-mediated immunity against various melanoma and breast cancer target cell cultures with a microcytotoxicity assay. Control lymphocytes inhibited growth of target cells with high frequency, particularly with cell line, as opposed to short-term, cultures. Inhibition was not found for all target cells tested at a given time with a single preparation of lymphocytes. Sequential studies over a 2-year period with lymphocytes from the same control donors showed fluctuations of inhibition against the same target cells. With serial passage, the target cells also changed in their susceptibility to destruction by control lymphocytes. Lymphocytes from melanoma patients were more inhibitory than control lymphocytes for one melanoma target cell culture but not for two other melanoma cultures. Significant inhibition by lymphocytes from melanoma patients was not seen against two cultures derived from breast cancer patients. Lymphocytes from breast cancer patients were more inhibitory than control lymphocytes for 4 of 5 breast cancer cultures and they did not inhibit two melanoma cultures. Significantly specific inhibition was seen with short-term, but not cell line, breast cultures. The over-all data show specificity for target cells of the appropriate histological type. However, the high and inconstant reactivity of control lymphocytes in this assay suggests that nonspecific inhibition of tumor target cells by patient lymphocytes is found in many experiments. It is concluded that the microcytotoxicity assay is not suitable for clinical studies, since sequential data obtained in individual patients are difficult to interpret.

Adult↗