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Biomedical subjects

G Della Porta

Publications and source records attributed to G Della Porta.

At least 55 records · Page 3Linked to original sources
PubMed1990

PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas.

We recently detected a novel activated oncogene by transfection analysis on NIH 3T3 cells in five out of 20 primary human thyroid papillary carcinomas and in the available lymph node metastases. We designated this transforming gene PTC (for papillary thyroid carcinoma). Here we describe the molecular cloning and sequencing of the gene. The new oncogene resulted from the rearrangement of an unknown amino-terminal sequence to the tyrosine kinase domain of the ret proto-oncogene. This gene rearrangement was detected in all of the transfectants and in all of the original tumor DNAs, but not in normal DNA of the same patients, thus indicating that this genetic lesion occurred in vivo and is specific to somatic tumors. Moreover, the transcript coded for by the fused gene was detected in an additional PTC-positive human papillary carcinoma for which mRNA was available.

Amino Acid Sequence↗
PubMed1990

t(11;22) in three cases of peripheral neuroepithelioma.

Short-term cultures of three cases of peripheral neuroepitheliomas were studied using G-banding technique. A t(11;22)(q24;q12) was recognized in all three tumors. The results strengthen the hypothesis of a common histogenesis for neuroepithelioma, Ewing's sarcoma, and the Askin tumor.

Adolescent↗
PubMed1990

Long-term assays for carcinogenicity.

During the past two decades, the rodent bioassay for detection of chemical carcinogens has reached a high standard of performance with both an increased number of animals and dose levels and a more detailed assessment of findings. However, the basic principles of testing and evaluation of results have remained essentially unchanged. Problems such as the length of the testing, use of maximum tolerated dose (MTD), selection of strains, variability of spontaneous tumors, discordant results between mouse and rat, and the classification of chemical carcinogens according to their mechanism of action have all remained unsolved. By contrast, the results of short-term tests and of other biological analyses do not always show a direct correlation with those of the long-term bioassays; this can be interpreted as an indication of different mechanisms of carcinogenicity. Currently available medium-term tests may detect carcinogenic activity of chemicals at particular organs in a period of time (weeks to months) relatively shorter than that of the 2-year carcinogenesis bioassay, and they may also provide additional information on mechanisms of carcinogenicity.

Animals↗
PubMed1990

Involvement of the region 13q14 in a patient with adamantinoma of the long bones.

A cytogenetic analysis of a lung metastasis of an adamantinoma of the tibia, a rare tumor of the long bones, revealed a karyotype 52, XY, t(7;13)(q32;q14), +7, +12, +13, +19, +der(7) t(7;13), +der(13) t(7;13). The t(7;13) was found to be constitutional in the patient and was also present in peripheral blood lymphocytes of his unaffected father. However, both subjects displayed normal levels of esterase D enzyme activity.

Ameloblastoma↗
PubMed1990

Chromosome abnormalities and fragile sites in human melanoma.

Chromosome analysis in short-term lines of three primary and seven metastatic malignant melanomas showed aneuploid karyotypes with recurrent abnormalities of chromosomes 1 (five cell lines), 6 (nine cell lines), and 7 (six cell lines). The breakpoints observed on the rearranged chromosomes frequently coincided with loci of known oncogenes and fragile sites. Two of the cell lines were analyzed after xenograft into nude mice and showed the presence of the same chromosomal changes observed in the parental cell lines, indicating the stability of the karyotype. A tendency toward an increased chromosomal fragility in peripheral blood lymphocytes was observed in five melanoma patients compared to ten normal individuals. However, there was no increased level of expression of specific fragile sites corresponding to the breakpoints observed in melanoma cells.

Chromosome Aberrations↗
PubMed1990

Cytogenetic study in therapy-related myelodysplastic syndromes (t-MDS) and acute non-lymphocytic leukaemia (t-ANLL).

A cytogenetic study was performed in 27 patients suspected of t-MDS or t-ANLL. In 12 patients the diagnosis of t-MDS or t-ANLL was confirmed by morphological, cytochemical and immunophenotypical analysis. The cases were classified as RA (one), RAEB (four), CMML (two), ANLL (five). They had received chemotherapy and/or RT for Hodgkin's disease (eight cases), solid tumours (three cases) and multiple myeloma (one case). Clonal chromosome abnormalities were found in bone marrow or peripheral blood cells in all the 12 cases. Five patients had a clonal abnormality of chromosome no. 5 (monosomy, deletions, translocation and inversion of 5q). The critical region on chromosome no. 5 comprised bands q12-q34. Monosomy and deletion of chromosome 7q was observed in the other two patients. In the six remaining patients various karyotypic patterns were observed including a t(4;11) (q21;q23) in one case, monosomies (four cases) and trisomies (one case) of different chromosomes. In the other 15 cases, the presence of a normal karyotype together with the morphological and immunophenotypical characterisation was consistent with a diagnosis of non-neoplastic specimens.

Adolescent↗
PubMed1990

Transgenic mice containing hepatitis B virus sequences are more susceptible to carcinogen-induced hepatocarcinogenesis.

Transgenic mice containing one copy of hepatitis B virus (HBV) genome without the core gene and expressing hepatitis B surface antigen (HBsAg) were crossed with C3H/He mice. The F1 hybrids (approximately 50% HBV positive and approximately 50% HBV negative) were treated with a single dose of diethylnitrosamine (NDEA) or p-dimethylaminoazobenzene (DAB) given at 7 days of age, or were untreated. Mice were kept under observation without further treatments until 30 weeks old and then killed. Stereological analysis of liver nodules and estimations of their size distribution demonstrated a significative enhancing effect of HBV transgene in both NDEA- and DAB-induced hepatocarcinogenesis in male mice. Hepatocellular adenomas and carcinomas were also more frequent in NDEA-treated HBV-positive than HBV-negative male mice. Female mice showed a lower tumorigenic response than males without significant differences between groups of HBV-positive and HBV-negative mice. It is proposed that the presence of the transgene enhanced carcinogen-induced hepatocarcinogenesis.

Animals↗
PubMed1990

Negative results of short-term genotoxicity tests with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene.

The phenobarbital-like enzyme inducer and tumor promoter of murine hepatocarcinogenesis, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene has been assayed in short-term genotoxicity tests, i.e. the Salmonella mutagenicity test, micronucleus and chromosomal aberrations analysis in mouse bone marrow cells in vivo, DNA alkaline elution and DNA unwinding assays in mouse liver in vivo. All the assays performed proved negative.

Animals↗
PubMed1990

Human TRK proto-oncogene maps to chromosome 1q32-q41.

The chromosomal localization of TRK, a gene coding for a putative receptor molecule with an associated tyrosine kinase activity that we have found activated in 25% of patients with papillary thyroid carcinoma, was determined by Southern blot analysis of a panel of human-rodent somatic cells using a cDNA clone containing the entire human TRK proto-oncogene (Martin-Zanca et al., 1986). The TRK gene was assigned to chromosome 1. One hybrid that had retained only the short arm of the human chromosome 1 was negative. Subsequently, in situ hybridization of the same probe to human metaphase chromosomes localized the TRK gene to 1q32-q41.

Blotting, Southern↗
PubMed1989

Clonal immunoglobulin gene rearrangements and normal T-cell receptor, bcl-2, and c-myc genes in primary cutaneous B-cell lymphomas.

Fourteen cases of primary cutaneous B-cell lymphomas were investigated at the immunohistochemical and molecular level to further characterize this newly defined entity. Neoplastic cells from all cases, phenotyped with a panel of monoclonal antibodies, were positive for HLA-DR, for the B-cell markers CD19, CD22, but not CD23 (except one case), and negative for the T-cell marker CD2. Monoclonal immunoglobulin light chains were demonstrated in six cases. The reactivity with the Ki-67 monoclonal antibody indicated that the neoplastic cells are proliferating. In five biopsies the presence of dendritic cells infiltrating the neoplastic areas was revealed using the monoclonal antibody Kim4b. By Southern blot analysis, clonal rearrangement of the immunoglobulin heavy chain gene (involving one or both alleles) was shown in 12 of 14 cases and of the light chain genes in 13 cases. The bcl-2 oncogene, normally involved in nodal follicular lymphomas, was in germ-line configuration. The c-myc and the beta and gamma chain genes of the T-cell receptor were also in the germ-line configuration. None of the cases presented Epstein-Barr virus sequences. These data indicate that primary cutaneous lymphomas of B-cell origin share morphological and phenotypic similarities with the nodal B-cell lymphomas of follicular histotype, are proliferating, and express in 45% of cases clear monoclonal immunoglobulin light chain; the molecular analysis confirms the B-cell derivation and the monoclonal nature of this neoplasia; it also shows that neither bcl-2 nor c-myc oncogenes are involved and that no inappropriate rearrangements of the T-cell receptor genes are found in this lymphoma.

Adult↗
PubMed1989

Onco-suppressor genes in human cancer.

The analysis of the molecular mechanisms governing multistep carcinogenesis became experimentally approachable since the identification and characterization in tumor cells of altered or activated versions of cellular genes (oncogenes) that normally control cell growth and differentiation. The activating mutations confer new properties to the oncogene products and should therefore be considered as gain of function mutations. In addition, the oncogenes appear to act as dominant genetic traits since they act also in the presence of the homologous wild-type allele. However, the concept of a dominance of the transformed phenotype has been challenged by early experiments with somatic cell hybrids which showed that the fusion of normal and malignant cells may suppress the tumorigenic phenotype. The suppression or reversion of the malignant phenotype by the introduction of a normal chromosome into a tumor cell line has lent support to the idea that a family of cellular genes are coding for factors capable to interact with the cell-growth control machinery. These genes seem to reconstitute the normal control of cell growth even in the presence of an activated oncogene. In addition, a two-mutation model has been proposed to explain the epidemiological and clinical features of childhood cancers. According to the model, the development of these malignancies can be caused by the loss or inactivation of both alleles of cellular genes, as suggested by the somatic cell hybrid experiments where the function of the inactivated genes is restored by the contribution of those derived from the normal parental cells. This family of genes is designated as onco-suppressor genes since their product is necessary for the normal regulated cell growth and is lacking or inactivated in malignant cells. At gene level they should be considered as recessive genetic traits, since the tumor phenotype appears when both alleles of an onco-suppressor gene are inactivated. The mutations affecting their normal functions belong to the type "loss of function". The molecular analysis of retinoblastoma has led to the cloning and sequencing of the related onco-suppressor gene (RB gene) whose product displays the features of a gene-regulatory protein. In addition, a binding between the RB product and various viral onco-proteins (E1A, large T, E7) has been demonstrated, thus suggesting a mechanism of RB inactivation by which some DNA viruses can transform the host cell.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1989

Cycloheximide increases endogenous retroviral RNA levels in murine liver and lung.

The expression of moloney murine leukemia virus (Mo-MuLV), intracisternal A particle (IAP), virus-like 30S sequence (VL30), early transposon (ET) endogenous retroviral sequences was analysed in the liver of untreated C3Hf, C57BL/6J and AKR mice, and in the lungs of untreated A/J, BALB/c, C3Hf and C57BL/6J mice. C3Hf mice are genetically susceptible to hepatocarcinogenesis, whereas the other strains are resistant. A/J and BALB/c mice are genetically susceptible to lung carcinogenesis, whereas the other strains are resistant. Both in liver and lung tissues we found differences between murine strains in the pattern of basal retrovirus expression. The effect of inhibition of protein synthesis on the levels of retroviral mRNAs was studied in the same tissues and strains 3 h following in vivo cycloheximide treatment. Cycloheximide treatment increased the liver and lung levels of virus Mo-MuLV, IAP, ET related transcripts in a strain dependent way, whereas VL30 mRNA levels increased in both tissues of all strains examined. These results suggested the existence of labile proteins that regulate the abundance of specific retroviral mRNAs in murine liver and lung in a strain specific fashion. No clear relationships between pattern of retrovirus expression and genetical susceptibility to hepatocarcinogenesis was found. The strains genetically resistant to lung carcinogenesis (C3Hf, C57BL/6J) showed higher lung basal levels and higher cycloheximide inducibility of mRNAs homologous to Mo-MuLV than the susceptible strains (A/J, BALB/c).

Animals↗
PubMed1989

Major urinary protein as a negative tumor marker in mouse hepatocarcinogenesis.

A cDNA clone isolated by differential screening of a mouse liver cDNA library using RNA probes from normal adult liver and from hepatocellular tumors showed, on northern blot analysis, a single transcript of 1 kb present at high levels in normal adult mouse liver but at 15- to 100-fold reduced levels in spontaneous and p-dimethylaminoazobenzene- or urethan-induced liver tumors. The transcript, which was absent in two-wk-old mouse liver, is coded by a developmentally regulated gene. Nucleotide sequence analysis demonstrated that the isolated clone encoded a major urinary protein (MUP). Immunocytochemistry analysis, using a goat antibody to MUP on histologic liver sections containing diethylnitrosamine-induced liver nodules, showed that the decrease in MUP levels also occurred in microscopic nodules. Therefore, MUP decrease represents an early event in the development of mouse liver tumors, and it may be used as a tumor marker in mouse hepatocarcinogenesis.

Alpha-Globulins↗
PubMed1989

Loss of heterozygosity in human germinal tumors.

The frequency of losses of heterozygosity has been investigated in 14 germinal tumors of the testis. Nonrandom deletion of whole or part of chromosome 11 was observed in four cases. In addition, loss of heterozygosity of all the informative loci analyzed was detected in one ovarian teratoma, indicating its post-meiotic origin. These results suggest that different genetic mechanisms (chromosomal deletions or meiotic segregation) that unmask putative recessive mutations are involved in the onset of germinal tumors.

Biomarkers, Tumor↗
PubMed1988

Morphologic, immunologic, and cytogenetic characteristics of secondary acute unclassifiable leukemia in Hodgkin's disease.

Blast cells from five cases of secondary unclassifiable leukemia following therapy for Hodgkin's disease were studied by cytochemical, immunological and cytogenetic analyses. Cytochemical and immunological reactivity were in accordance with poorly differentiated, myeloid blasts. The four cases in which karyotype analysis was performed showed specific chromosomal abnormalities. No evidence of multiple lineage involvement was found. Problems in classifying these cases of secondary ANLL were due to the high grade of undifferentiation of the blast cells. Their low cytochemical reactivity with markers of myeloid differentiation was similar to what may be observed in patients with acute undifferentiated leukemia or with chronic myeloid leukemia in blast crisis.

Adult↗
PubMed1988

Cytogenetic studies in primary and metastatic neuroendocrine Merkel cell carcinoma.

Direct preparations of five primary and metastatic neuroendocrine Merkel cell carcinomas of the skin were analyzed using a G-banding technique. A recurrent structural abnormality was a rearranged chromosome #1 with involvement of p and q arms. In two cases this rearrangement appeared as a unique structural cytogenetic change. Evidence for clonal origin and karyotypic stability of this tumor was suggested by the occurrence of the same karyotypic changes in two metachronous metastases and in primary and metastatic tumor specimens of two different patients. The bands involved in rearrangements could be of significance in the molecular process of the neoplastic transformation of Merkel tumor because genes relevant to the differentiation of neural crest-derived tissue have been mapped in those regions.

Adenocarcinoma↗