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Biomedical subjects

G Carbone

Publications and source records attributed to G Carbone.

At least 37 records · Page 2Linked to original sources
PubMed1992

Can oncogene (RAS) activation predict susceptibility of human melanoma to activated lymphocytes and, therefore, the clinical response of such neoplasms to adoptive immunotherapy?

The expression of activated ras oncogenes was found to be associated with that of tumour-specific transplantation antigens in mouse tumours, which can be cured by adoptive immunotherapy with T lymphocytes and interleukin-2 (IL-2). A similar association is here proposed to exist between RAS oncogene activation (mutation) in human melanoma and susceptibility of these tumours to the lytic action of activated lymphocytes (both lymphokine-activated killers and cytotoxic T cells) which have been used, along with IL-2, in the adoptive immunotherapy of advanced melanomas. The limited clinical response (15-25%) of melanoma patients to different immunological therapies is, therefore, considered to be due to a similar frequency of immunogenic, RAS+ melanomas. The authors thus suggest that RAS activation might be a marker of immunogenicity and that only the subset of melanoma cells expressing activated RAS will in turn possess tumour antigens which can be the target of immunotherapeutic, activated lymphocytes. It is then predicted that RAS+ melanomas will be more susceptible to adoptive immunotherapy than RAS-counterparts.

Animals↗
PubMed1991

Activation of ras oncogenes and expression of tumor-specific transplantation antigens in methylcholanthrene-induced murine fibrosarcomas.

The DNA of 22 fibrosarcomas, newly induced in BALB/c mice by subcutaneous doses of 3-methylcholanthrene (3-MCA), was tested in NIH 3T3 transformation assay. Activation of K-ras and N-ras was found in 7 and 3 cases respectively. No H-ras activation was detected. Polymerase chain reaction and oligonucleotide hybridization performed on the DNA of the 22 sarcomas revealed 5 cases of K-ras mutation at codon 12, 3 at codon 13 and 1 at both codons. One case of K13 mutation was not detectable by transfection. Three cases of mutation at codon 61 of N-ras were also found, one of which was simultaneous with a K12 mutation. Tumor-specific transplantation antigens (TSTA) were assessed in the 22 original tumors. Altogether 16 sarcomas were immunogenic, with the highest frequency of TSTA+ tumors (10/11 and 5/6) in the groups given 1.0 and 0.1 mg of 3-MCA respectively, the lowest (1/5) in that with 0.01 mg of carcinogen; ras mutations occurred in the DNAs of 11 out of the 16 TSTA+ sarcomas, but none of the DNAs of the 6 TSTA- tumors showed ras mutation. The results suggest that 3-MCA-induced transformation of subcutaneous fibroblasts can involve mutations in codons 12, 13 or 61 of K- and N- but not H-ras gene and that such mutation is accompanied by the expression of TSTA.

Animals↗
PubMed1990

H-2 class I gene analysis in 3-methylcholanthrene-induced murine fibrosarcomas.

The objective of our study was to determine whether and how frequently MHC class I gene alterations occur in fibrosarcomas induced in BALB/c mice by the carcinogen 3-methylcholanthrene (3-MCA). Southern blot was performed to analyze the genomic organization of class I genes in a panel of twenty tumors of different immunogenic strength used at early in vivo passages. Our results rule out the presence of gross rearrangements or deletions in the H-2 class I genes of the tumors tested and indicate that the frequency of detectable class I alterations giving rise to restriction fragments length polymorphism (RFLP) should be very low.

Animals↗
PubMed1990

Multiple sclerosis. Magnetic resonance imaging, evoked potentials and cerebrospinal fluid analysis.

We have studied 27 patients with multiple sclerosis (22 definite, 5 probable) by magnetic resonance imaging (MRI), visual evoked potentials (VEPs), brainstem auditory evoked potentials (BAEPs), and oligoclonal bands (OBs) in cerebrospinal fluid (CSF), MRI was altered in 92.5% of the cases, the presence of OBs in CSF was revealed in 73.1% of the examined patients, the frequency of evoked potentials (EPs) alteration was VEPs = 59.3% and BAEPs = 29.6%, at least one of the two EPs occurred positive in 66.6% of the cases. Our data confirm the more sensitive value of MRI compared with OBs and EPs studies in assessing MS, and stress the utility of the combined use of these tests.

Adolescent↗
PubMed1989

Expression of retrovirus-related, cytotoxic T lymphocyte- and transplantation-defined antigens in NIH/3T3 transfectants after a single passage in nude mice.

Transfection of T24c-Ha-ras oncogene into NIH/3T3 fibroblasts resulted in the establishment of a transformed cell line (pT) that was tumorigenic when injected s.c. both into Swiss outbred nude mice and normal NIH inbred mice. The passage into nude mice, however, led to the development of a tumor variant (pT-nude) able to subsequently grow into sublethally x-irradiated but not into immunocompetent NIH mice. NIH mice immunized with this tumor variant developed a strong specific CTL response against the immunizing cell line, whereas the parental transformed pT cell line was not lysed. Clones were derived by limiting dilution from anti-pT-nude bulk population and were tested on a panel of transformed NIH/3T3 lines before and after their growth as tumor into nude mice. All of these lines were lysed by the Lyt-2+ CTL clones as a sole consequence of one in vivo passage into nude mice. The cross-reactive Ag were shown to be related to endogenous retroviral products as assessed by 1) immunoprecipitations of gp70, p15E, and p30 viral proteins in the nude variants but not in parental lines, and 2) by the ability of retroviruses from irradiated pT-nude cells to infect NIH/3T3 or pT lines making them susceptible to lysis by anti-pT-nude CTL clones. These results show that a single passage in nude mice can induce retrovirus-related, cell-surface Ag in transplanted neoplastic cells.

Animals↗
PubMed1988

Activated c-K-ras and c-N-ras oncogenes in 3-methylcholanthrene-induced BALB/c fibrosarcomas.

DNAs from fourteen fibrosarcomas induced by 3-methylcholanthrene (MCA) in BALB/c mice were analyzed for the presence of transforming oncogenes following transfection on NIH3T3 cells. Six transfection-positive DNAs contained an activated ras gene: four c-K-ras and two c-N-ras. These results demonstrate that c-K-ras is not the only oncogene of the ras family activated in MCA-induced murine fibrosarcomas as was previously indicated.

Animals↗
PubMed1987

Cerebrospinal fluid protein findings during prophylaxis and treatment of neuromeningosis in leukaemic patients.

Methotrexate and Aracytin commonly employed in prophylaxis and treatment of leukaemic neuromeningosis, can induce neuromeningeal injury. Cerebrospinal fluid (CSF) protein disturbance may reflect the damage. In this study we have examined 141 CSF samples collected by lumbar puncture from 51 subjects: 15 normal controls and 36 leukaemic patients during the prophylaxis or the Central Nervous System (CNS) involvement treatment. In all the CSF samples, total proteins, IgG and IgA were examined. CSF total protein and albumin levels increased in the presence of leukaemic neuromeningosis and also after a prolonged CNS prophylaxis or therapy. The same behaviour was found in IgG levels. The IgA levels did not show any modification. We conclude that these parameters are not reliable indices of leukaemic CNS involvement.

Adult↗
PubMed1985

Cell surface antigens of chemically induced fibrosarcomas: detection by a monoclonal antibody of a tumor-restricted Mr 12,000 protein gag antigen encoded by a dual-tropic murine leukemia virus.

Fusion products of spleen cells of W/FuDp rats immunized with a methylcholanthrene-induced BALB/c sarcoma, CA-2, and mouse myeloma cells were screened in an attempt to identify a monoclonal antibody defining the individually distinct tumor-specific transplantation antigen of CA-2. A hybridoma, MP/69/04, was isolated which produces an IgG2a monoclonal antibody that recognized a tumor-restricted antigen of CA-2. In direct binding assay, MP/69/04 reacted only with 2 of 15 methylcholanthrene induced BALB/c sarcomas tested. Thymus, spleen, lymph nodes, bone marrow, brain, adult lung fibroblasts, newborn muscle fibroblasts and 3T3 cells were negative. Absorption tests revealed, however, expression of the MP/69/04 determinant on 8 of the 12 murine leukemia virus (MuLV) producer BALB/c sarcoma tested. The antigen was not detected on any of the three non-producer sarcomas tested nor on a wide range of normal tissues and cell lines. An N-dualtropic MuLV was isolated from CA-2, and cell lines susceptible to infection by this virus were shown to express the MP/69/04 epitope. By Western blotting, the MP/69/04 epitope was identified as being expressed on the MuLV structural protein with a molecular weight of 12,000, present in CA-2 cells and in the purified CA-2 MuLV. These results indicate the MP/69/04 antigen is not a unique tumor-specific transplantation antigen but is a gag product of a recombinant retrovirus which is expressed on the cell surface of many MuLV + methylcholanthrene-induced BALB/c fibrosarcomas.

Animals↗
PubMed1983

In vitro detection of cell-mediated immunity to individual tumor-specific antigens of chemically induced BALB/c fibrosarcomas.

In this study we have analyzed the in vitro cell-mediated cytotoxicity of immune peritoneal exudate cells (PEC), elicited in syngeneic mice against the MCA-induced, TSTA-bearing BALB/c fibrosarcoma CA-2, GI-17 and C-3. The 4 h 51Cr-release assay showed the immune PEC effectors to be specifically cytotoxic to fibrosarcoma used for the immunization, but not to other syngeneic MCA-induced tumors or normal fibroblasts. Cold target inhibition experiments on CA-2 cells confirmed the specificity of the reaction. When PEC, lymph-node and spleen cells from BALB/c anti-CA-2 mice were compared for anti-tumor activity, only PEC were found to kill tumor cells significantly. PEC effectors did not have a significant level of NK or NC activities since they were unable to destroy YAC-1 or WEHI-164 tumor cells. PEC anti-CA-2 were analyzed for the expression of T-cell markers by anti-Thy 1.2, anti-Ly 1.2 and Ly 2.2 monoclonal antibodies. Anti-tumor specific effector cells were identified as mature T cells since they were not adherent to plastic and showed Thy 1.2+, Ly 1.2- and Ly 2.2+ phenotypes. In addition, anti-H-2Kd but not anti-H-2Dd alloantiserum added to target cells, blocked CA-2 tumor lysis, thus supporting the conclusion that the T-cell response against TSTA is H-2 restricted.

Animals↗