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Biomedical subjects

L Milas

Publications and source records attributed to L Milas.

At least 181 records · Page 10Linked to original sources
PubMed1979

Activation of pleural macrophages by intrapleural application of Corynebacterium parvum.

A single ipl injection of 0.25 mg CP into CBA mice led to accumulation of macrophages in the pleural cavity, but it did not influence RES as an injection given iv ipl CP caused a three-to-five-fold increase in the number of nucleated cells in the pleural cavity which persisted at least 14 days. Of these cells 86% were macrophages as shown by their esterase activity. Less than 30% of cells from the pleural cavity of normal mice were esterase positive. Macrophages from the pleural cavity of CP-treated mice were capable of destroying in vitro cultures of a syngeneic mammary carcinoma, while normal pleural macrophages exerted no effect; the former were not cytotoxic for either syngeneic or allogeneic embryo fibroblasts. Ipl CP protected mice against iv injected mammary carcinoma cells; given to mice 7 days after iv inoculation of tumor cells it significantly reduced the number of tumor nodules in their lungs.

Animals↗
PubMed1978

Modification of radiation responses of murine tumors by misonidazole (Ro 07-0582), host immune capability, and Corynebacterium parvum.

The hypoxic cell sensitizer misonidazole (Ro 07-0582),1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol, significantly enhanced the local control of the weakly immunogenic C3H mouse mammary carcinoma MDAH-MCa-4 (8-mm diameter) by single doses of radiation. The dose modification factor (DMF) was 2.33 when the drug was given ip to inbred C3Hf/Bu mice in a dose of 1 mg/g body weight 30 minutes before irradiation of the tumor. The DMF in a highly immunogenic 3-methylcholanthrene-induced C3H fibrosarcoma (FSa) was 1.65 in normal mice and 1.86 in mice immunosuppressed by 600 rads whole-body irradiation 1 day before tumor transplantation. In mice treated iv with 0.25 mg Corynebacterium parvum when tumors were 6 mm in diameter and irradiated at 8 mm, local control of FSa was enhanced at low doses of radiation but was similar to that in normal mice at higher doses. In mice treated with both misonidazole and C. parvum, local control at lower doses of radiation was similar to that in mice treated with C. parvum alone but was enhanced at higher doses in mice that failed to respond to C. parvum. Cytotoxicity of misonidazole, as reflected in tumor growth, was not detected.

Animals↗
PubMed1977

The distribution and persistence in vivo of Corynebacterium parvum in relation to its antitumor activity.

Killed Corynebacterium parvum was labeled with fluorescein isothiocyanate or 125I, and both preparations were shown to retain lymphoreticular stimulatory and antitumor activity. Large amounts of C. parvum injected i.v. were found in the liver, spleen, and lungs with less in bone marrow and lymph nodes. Apart from a rapid loss from the lungs within 24 hr, the persistence of killed C. parvum was striking, and some intact bacteria were still detectable in the liver and spleen at 15 days. (By contrast, the breakdown of an inactive C. parvum strain in the liver was considerably faster). The blood clearance of 125I-labeled C. parvum injected i.v. into tumor-bearing mice was more rapid than in normal mice, and the absolute, but not the unit, amounts of C. parvum taken up by the spleen and tumor-draining node were increased. 125I-labeled C. parvum was found within the body of established solid tumor, but there was no correlation between the amounts of C. parvum taken up by various mouse solid tumors after i.v. injection and their susceptibility to i.v. C. parvum therapy. The distribution and persistence of C. parvum injected into a tumor lesion was similar to that after s.c. injection. The bulk of the inoculum was retained at the injection site and draining lymph node. Contralateral nodes were unlabeled, and uptake in the liver and spleen was considerably less than after i.v. injection. Although no C. parvum was found in peritoneal cells after i.v. injection, the macrophages in this population became activated and were capable of nonspecifically inhibiting tumor cell growth in vitro.

Animals↗
PubMed1976

Nonspecific immunotherapy of malignant tumors.

At present, nonspecific immunotherapy of malignant tumors seems to be the most promising among immunotherapeutic modalities. Potent nonspecific immunostimulants, Bacillus Calmette-Guerin (BCG) and Corynebacterium parvum, exhibit an antitumor activity in experimental animals, which is commonly manifested by reduced tumor growth and sometimes by complete regression of tumors. Antitumor effectiveness of these bacteria is largely related to tumor immunogenicity and host immunocompetence. Recently, BCG has frequently been used for clinical immunotherapy and has provided therapeutic benefit in many instances, particularly when combined with chemotherapy, radiotherapy or surgery. Clinical experience with C. parvum is so far limited.

Adjuvants, Immunologic↗
PubMed1975

Combination of C. parvum and specific immunization against artificial pulmonary metastases in mice.

We have studied whether specific immunization administered intraperitoneally can augment the activity of C. parvum (0.25 mg intraperitoneally or intravenously) against intravenously injected cells of a syngeneic fibrosarcoma in C3Hf/Bu mice as expressed by the reduction of pulmonary metastases (nodules, colonies) and/or by the prolongation of the survival of recipients. Combination of specific immunization and C. parvum, applied either before or after IV inoculation of viable tumor cells, was more effective than the single treatments. IV injection of a mixture of heavily irradiated and viable tumor cells gave more tumor nodules in the lungs of normal mice than injection of viable cells alone. The metastasis-enhancing effect of admixed irradiated cells was not found in mice previously treated with C. parvum, and was abolished if the immunostimulant was injected after tumor cells. Generation of lung metastases by IV inoculation of fibrosarcoma cells was reduced in mice already having this tumor in the leg. This concomitant immunity to metastases was increased by treating the recipients with C. parvum, but not with irradiated cells; also, the injection of irradiated cells together with C. parvum did not augment the efficiency of the latter. C. parvum was not as effective in T-cell deprived as in control mice, which suggests that in this system, T-cells are required for optimal anti-tumor activity of this immunostimulant. Specific immunization was not effective in T-cell-deprived mice and did not augment the efficiency of C. parvum.

Animals↗
PubMed1975

In vitro destruction of tumor cells by macrophages from mice treated with Corynebacterium granulosum.

Peritoneal macrophages from C3Hf/Bu mice treated with killed Corynebacterium granulosum bacteria were tested for their effect on in vitro growth of syngeneic fibrosarcoma cells, tumorigenic mouse L-P59 cells, human malignant melanoma cells, allogeneic fibroblasts, erythrocytes, and epithelial kidney cells. Only the cell cultures having neoplastic properties were destroyed by stimulated macrophages; the rate of tumor cell destruction was greater as the ratio of effector to target cells was increased. Neither irradiation nor trypsinization of macrophage monolayers altered the cytotoxicity of stimulated macrophages. The results indicated that C. granulosum activated macrophages to destroy tumor cells in an immunologically nonspecific manner but had no cytotoxic effect on normal allogeneic cells.

Animals↗
PubMed1975

Nonspecific Immunotherapy of Murine Solid Tumors With Corynebacterium granulosum.

A single intraperitoneal (ip) or intravenous (iv) injection of Corynebacterium granulosum into C3Hf/Bu mice shortly after subcutaneous (sc) injection of cells from a strongly antigenic syngeneic fibrosarcoma induced by 3-methylcholanthrene caused complete and lasting regressions of 100 and 70% of resulting tumors, respectively. Treatment with this bacterium sc only slightly inhibited the growth of some tumors. C. granulosum given iv to mice 3 days after the sc injection of fibrosarcoma cells caused complete regressions of 39 of 45 tumors; two iv injections with this immunostimulant given 1 month apart were no more effective than a single injection. Intralesional treatment of fibrosarcomas 8 mm in diameter induced complete regressions of tumors in 30% of the animals, whereas sc treatment contralateral to the growing tumor only slightly reduced tumor growth. Intraperitoneal growth of a fibrosarcoma was efficiently controlled (58-80% survival of mice) if C. granulosum was given ip, but not iv, 3 days after inoculation with tumor cells. Again, two injections of C. granulosum (given ip 4 days apart) were only as effective as a single injection. Treatment with C. granulosum iv at 3, 7, 14, or 21 days after sc inoculation of a weakly antigenic, spontaneously arising mammary carcinoma (MC-1) strongly inhibited tumor growth. Three complete but temporary tumor regressions were observed. The subcutaneous growth of another spontaneous mammary carcinoma (MC-2), which contained fairly strong tumor-specific antigen(s), was also significantly inhibited if C. granulosum was given 3,7, or 14 days after, but not 7 days before, tumor cell inoculation. However, pretreatment of mice with the immunostimulant significantly protected the mice against artifically induced pulmonary metastases of this tumor.

Animals↗
PubMed1975

Effects of Corynebacterium granulosum on weight and histology of lymphoid organs, response to mitogens, skin allografts, and a syngeneic fibrosarcoma in mice.

We studied the effect of single and multiple injections of Corynebacterium granulosum on weight and histology of lymph nodes and spleen, on peripheral white blood cell count, response of peripheral blood lymphocytes, lymph node, and spleen cells to phytohemagglutinin and pokeweed mitogen, survival of skin allografts, and lung metastases of a syngeneic fibrosarcoma in C3Hf/Bu mice. Corynebacterium parvum was used in some studies on antitumor activity. The weight of lymph nodes and spleen was markedly increased by single and multiple i.p. injections of C. granulosum, the peak enlargement occurring at Day 7 in lymph nodes and at Day 16 in spleen. Histologically, there was an extensive proliferation of nucleated cells in the enlarged organs. C. granulosum did not change the total white blood cell count but caused a temporary lymphopenia. In general, in vitro response to phytohemagglutinin and pokeweed mitogen of blood lymphocytes and spleen cells was decreased. Lymph node cell response to phytohemagglutinin was increased by small doses (0.025 mg) of C. granulosum, was not altered by a single large dose (0.5 mg), and was decreased by multiple doses. The response of lymph node cells to pokeweed mitogen was increased by all treatments. These changes in response to mitogens were demonstrable for about 2 months after treatment. Treatment i.v. with 0.1 or 0.25 mg of C. granulosum given before but not after grafting significantly prolonged the survival of grafted BALB/c skin. Smaller doses of this bacterium were not effective. Splenectomy of skin graft recipients did not prevent the effect of C. granulosum. Treatment i.p. or i.v. with this bacterium significantly decreased the number of lung metastases from i.v.-injected fibrosarcoma cells, even if the cells were injected 3 to 4 months later. The magnitude of this effect varied with the dose and frequency of injection of C. granulosum and C. parvum.

Actinomycetales↗