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Biomedical subjects

G Rovera

Publications and source records attributed to G Rovera.

157 records · Page 9Linked to original sources
PubMedDate not supplied

Nucleotide sequence of cloned cDNA of human c-myc oncogene.

Like other transforming genes of retroviruses, the v-myc gene of the avian virus, MC29, has a homologue in the genome of normal eukaryotic cells. The human cellular homologue, c-myc, located on human chromosome 8, region q24 leads to qter (refs 1, 2), is translocated into the immunoglobulin heavy-chain locus on human chromosome 14 (ref. 3) in Burkitt's lymphoma, suggesting that c-myc has a primary role in transformation of some human haematopoietic cells. In addition, c-myc is amplified in the human promyelocytic leukaemia cell line, HL60 (refs 6, 7) which also contains high levels of c-myc mRNA. Recently, Colby et al. reported the nucleotide sequence of the human c-myc DNA isolated from a genomic recombinant DNA library derived from human fetal liver. This 4,053-base pair (bp) sequence includes two exons and one intron of the myc gene, and the authors have suggested the existence of a human c-myc mRNA of 2,291 nucleotides that has a coding capacity for a protein of molecular weight (Mr) 48,812. We have approached the problem of accurately defining the characteristics of the human c-myc mRNA and c-myc protein by determining the sequence of the c-myc cDNA isolated from a cDNA library prepared from mRNA of a clone of the K562 human leukaemic cell line. K562 cells are known to contain c-myc mRNA which is similar in size to the c-myc mRNA of other human cell types. We report here the sequence of 2,121 nucleotides of a human c-myc mRNA and demonstrate that its 5' noncoding sequence does not correspond to the sequence of the reported genomic human sequence. However, our data confirm that the intact human c-myc mRNA can encode a 48,812-Mr protein with a sequence identical to that reported by Colby et al.

Amino Acid Sequence↗
PubMedDate not supplied

Association of amplified oncogene c-myc with an abnormally banded chromosome 8 in a human leukaemia cell line.

Several unusual chromosome structures have been described in drug-resistant cell lines and in certain tumours. These structures include elongated homogeneously staining regions (HSRs), small extrachromosomal paired chromatin bodies (double minutes, DMs) and abnormally banded regions (ABRs) with strong but anomalous band patterns. There is evidence that these are alternative forms of gene amplification, with HSRs breaking down to form DMs, and DMs integrating into the chromosome to generate HSRs and ABRs. Recently, it was demonstrated that, compared with several normal and leukaemia human cells, DNA sequences representing the human homologue of the onc gene of the avian myelocytomatosis virus (MC29), the so-called c-myc gene, were amplified in HL-60 cells. This is a human promyelocytic leukaemia cell line established in the laboratory of one of us (R.C.G.) at the National Cancer Institute (Bethesda, Maryland) in 1977, and widely used for studies on myeloid and monocytic differentiation. Amplification of the gene was present in primary leukaemic cells of the patient, and DMs were noted in some of these cells as well as in early passages of the HL-60 line. No structure resembling HSRs or ABRs were noted in karyotypic studies at this early stage and there were no alterations involving the long arm of chromosome 8 (8q), to which the c-myc gene has recently been mapped. We have now re-examined the karyotype of the HL-60 line, using cells frozen at various times during its continuous passage at the Wistar Institute (Philadelphia, Pennsylvania) to look for chromosomal abnormalities that might be associated with the amplification of c-myc. We find that, beginning in 1979, HL-60 cells at the Wistar Institute no longer had DMs, but did show an abnormal 8q+ chromosome, replacing a normal chromosome 8, and representing an ABR reflecting the site of myc gene amplification.

Cell Line↗
PubMedDate not supplied

A novel human lymphokine that inhibits haematopoietic progenitor cell proliferation.

T lymphocytes in culture synthesize and secrete a variety of factors that activate and guide the differentiation, replication and maturation of haematopoietic cells in vitro. Malignant T-cell lines as well as T-cell hybridomas producing several of these factors have been established. We report here a factor produced by a human cell line that exerts a potent inhibitory effect on the growth of bone marrow progenitor cells. The properties of this factor, which we have termed colony-inhibiting lymphokine ( CIL ), differ from other inhibitors of haematopoietic progenitor cell proliferation, but resemble those of a T-cell-derived factor causally linked with some cases of severe aplastic anaemia in humans. Sensitivity of cells to this factor appears to correlate positively with expression of HLA-DR surface antigens.

Bone Marrow↗
PubMedDate not supplied

Synergistic effects of adriamycin and TALL-104 cell therapy against a human gastric carcinoma in vivo.

The single and combined antitumor effects of adriamycin and a major histocompatibility complex non-restricted human cytotoxic T cell line (TALL-104) were evaluated in severe combined immunodeficient (SCID) mice engrafted subcutaneously with a biopsy sample from a patient with a highly metastatic gastric carcinoma. Chemotherapy was initiated 3 weeks after tumor implantation, when local growth was advanced, and consisted of 2 weekly injections of adriamycin. gamma-irradiated (40 Gy) TALL-104 cells were administered daily for 2 weeks, starting 1 day after the end of chemotherapy. While TALL-104 cells or adriamycin alone did not inhibit tumor growth, synergistic antitumor effects were seen with the two treatments combined. These findings suggest that chemotherapy in conjunction with cell therapy are effective in overcoming tumor resistance to single therapeutic agents through mechanisms independent from the host immune system.

Animals↗