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Biomedical subjects

G Fossati

Publications and source records attributed to G Fossati.

At least 145 records · Page 8Linked to original sources

High incidence of chromosomal lesions involving C-heterochromatin in four human melanoma lines.

Cytogenetic analysis of early in vitro cultures derived from human melanomas, two primary tumors (Me 10538, Me 1402) and two metastatic lesions in the same patient (Me 665/1, Me 665/2) showed non-random involvement of C-heterochromatin in clonal chromosome rearrangements. Marker chromosomes with C- and DA-Dapi-positive bands were identified in one of the metastases, Me 665/1 (m1) and in the two primary tumors, Me 10538 (m2) and Me 1402 (m3). C-positive fragments predominated in the other metastasis, Me 665/2, which lacked C-regions intercalated in rearranged chromosomes, and were also detected with appreciable frequency in the Me 665/1 and Me 1402 cells. The frequencies of marker chromosomes and their mean number per cell allowed m2 and m1 to be considered as early markers of tumor formation and m3 as a marker of tumor progression. Dissection of chromosome structure, including the origin of the intercalated C-band, has so far been achieved only with the m2 chromosome of the primary tumor Me10538. This was the only cell line which displayed few C-fragments and a narrow chromosomal distribution with a well defined mode. A gradient of malignancy could be detected in the four cell lines, by local and disseminated tumor growth in xenotransplanted mice, with the two primary melanomas 10538 and the 1402 cells at the lowest and upper extremes. This gradient closely parallels the increase in cytogenetic heterogeneity and C-heterochromatin lesions from the 10538 to the 1402 cells.

Chromosome Aberrations↗

Adoptive immunotherapy of cancer with immune and activated lymphocytes: experimental and clinical studies.

Recent studies of passive adoptive immunotherapy of experimental tumors indicate that histologically different neoplasms can be cured by this procedure in mice, rats and guinea pigs. In this paper two main approaches of adoptive immunotherapy with lymphocytes are considered. One which makes use of specific tumor-immune cells and is applicable to immunogenic tumors, and the other which uses activated (allostimulated and/or IL-2-activated) lymphocytes and is applicable to immunogenic and non-immunogenic neoplasms. Experimental models of both approaches and results provided by them are reviewed. These studies indicate that transfer of tumor-reactive lymphocytes with or without the combined administration of IL-2 into syngeneic tumor-bearing animals can lead to the eradication of a disseminated neoplasia when certain conditions are met. In particular, it was found that high tumor burdens, delay of treatment and low number of transferred lymphocytes can adversely affect the results. It has also been shown that the therapeutic effect of treatment with anti-cancer drugs or irradiation may be significantly improved by the addition of adoptive immunotherapy. The successful treatment of immunogenic tumors often requires the inhibition of suppressor lymphocytes by Cy or irradiation. Non-immunogenic tumors can be successfully treated only by providing activated lymphocytes and high doses of IL-2. Recent findings of few available human studies of adoptive immunotherapy are also reviewed, and the problems of toxicity and possible therapeutic effects of infusion of autologous, activated lymphocytes and IL-2 are discussed.

Animals↗

The undefined relationship between tumor antigens and histocompatibility antigens on cancer cells.

The data pertaining to the possible relationship between histocompatibility antigens (HA) and tumor-specific transplantation or tumor surface antigen (TSTA or TSA) are reviewed. The HA profiles of certain experimental and human neoplasms have been found to be altered either from the quantitative (increased expression of some antigenic specificities and decreased expression or even lack of other HA) or qualitative point of view (appearance of alien, genetically inappropriate HA). The authors entertain the possibility that the persence of TSTA or TSA on cancer cells may be linked to alterations of the HA profile. Evidence in favour of the idea that tumor antigens may actually to alien MHC products, alien minor HA or modified HA, is reviewed. Findings on structural relationships between TSA and beta2-microglobulin are also summarized. In the authors' opinion, no definitive conclusions can be reached at the present time on the relationship between TSTA or TSA and HA of cancer cells.

Animals↗

Phenotypic heterogeneity of HLA products on human melanoma cells.

The expression of class I and class II HLA antigens has been studied on primary and metastatic human melanomas, and on cell clones derived from the latter. A panel of monoclonal antibodies and flow cytofluorometric analysis were used to evaluate the presence of HLA-A, B, C and -DR, DQ antigens on freshly isolated tumour cells. HLA class I antigens were present on 91% and 93% of primary and metastatic tumours, respectively. Sixty per cent of primary and 50% of metastatic melanomas expressed HLA-DR antigens, whereas 38% and 21% of cases were positive for HLA-DQ. A marked heterogeneity was evident among primary and metastatic lesions for expression of class I and II antigens. Similar findings were obtained by analysing the phenotype of melanoma clones which indicates that a marked antigenic heterogeneity for class I and II HLA antigens occurs even among clones isolated from short-term cultures of metastatic melanomas.

Antibodies, Monoclonal↗

Loss of polymorphic restriction fragments of class I and class II MHC genes in a malignant melanoma.

DNAs from human malignant melanoma cells and autologous peripheral blood lymphocytes were evaluated by Southern blot analysis with probes for class I and II HLA genes. DNA of melanoma cells digested with PvuII, EcoRI and BglI and hybridized with a DR beta probe showed a loss of several fragments when compared with DNA from lymphocytes. The same DNAs were not distinguishable when hybridized with a DQ beta probe. Analysis of melanoma and autologous lymphocyte DNAs from the same patient with a class I cDNA, after digestion with several endonucleases, revealed a further loss of fragments in melanoma cells. Comparison of restriction fragment patterns of melanoma and lymphocytes with those of homozygous, serologically-typed cell lines indicated that melanoma cells have lost fragments diagnostic of DR2 and A1 antigens. A densitometric analysis of signals of several oncogenes in comparison with that of DR indicated that a duplication of the remaining DR allele had occurred in melanoma cells.

DNA, Neoplasm↗

Complement-dependent serum cytotoxicity of cancer patients studied by 51Cr release assay on human cancer lines.

The conditions for a 51Cr release assay on cell lines derived from human solid tumors were determined by using a rabbit antihuman antiserum with human AB serum as source of complement. By this assay 38 sera collected before and after surgery from 19 breast cancer patients and 28 sera from 12 melanoma patients and 16 healthy donors were tested on 3 lines derived from breast cancer tissue and 1 line derived from normal breast tissue. Ten of the breast cancer patients had lymph node metastases and 9 did not. Positive reactions were obtained from 4 breast cancer patients, all with lymph node metastases, and from 1 healthy donor. In a second experiment, 58 coded sera belonging to 4 different groups of cancer and non-cancer individuals were assayed on a colonic cancer line (HT-29), and 33 and 20 of them were also treated on a melanoma line (MeWo) and on a breast cancer line (MaCa 13), respectively. Positive responses were few, and were more frequently observed among transfused than non-transfused patients.

Animals↗

[Pulmonary hemosiderosis induced by cow's milk proteins: a discussion of a clinical case].

Pulmonary hemosiderosis (PH), a rare pathology, usually occurring during infancy and childhood, is characterized by numerous and repeated intra-alveolar bleedings, interstitial iron build-up with consequent progressive fibrosis and severe anemia. PH can be basically divided into 3 different categories: Primitive or idiopathic, involving a primitive deficit of antioxidizing enzymes in the erythrocytes in genetically predisposed subjects; Secondary, subsequent to chronic pneumopathy or cardiopathy; Associated with various pathologies including collagenopathies, glomerulonephritis, myocardiopathies, diabetes, steatorrhea, tireotossicosis. A particular type of Pulmonary Hemosiderosis, associated with allergy to cow's milk, has been described for the first time by Heiner. We present in this paper our personal experience of a young patient suffering from pulmonary hemosiderosis induced by cow's milk protein.

Child↗

[New therapeutic trends in thalassemia: oral chelating agents].

The future therapeutic strategy for decreasing iron overload in poly-transfused patients will include oral chelation. The product currently undergoing the most intensive experimentation is Ll (1,2-dimethyl-3-hydroxypyrid-4-one). We report here a short-term efficacy study carried out in 10 thalassemic transfusion-dependent pediatric volunteer patients, already closely followed in our Day Hospital, after having provided their informed consent. In our study Ll, when compared to Desferrioxamine, was clearly efficacious and safe.

Administration, Oral↗

[Iron deficiency in children: which is the correct therapy?].

Iron is essential for human metabolism. Under normal circumstances its homeostasis is strictly kept by absorption and excretion through genitourinary, gastrointestinal tracts and skin losses. In several systemic disorders, dietary iron is insufficient to keep such a dynamic balance: development of iron deficiency may be due to increased requirements, decreased intestinal absorption, inadequate dietary uptake. Low birth weight newborns, children and adolescents are at increased risk for developing iron deficiency. Although clinical aspects may vary, hematochemical findings show a three-step gradual progression. In a first step iron deficiency is diagnosed by serum ferritin level which will be under 10-20/micrograms/ml showing a depletion of total body iron stores. In a second step progressing iron deficiency will be assessed by lowered serum iron and increased unsaturated serum transferrin, serum iron bound to transferrin and erythrocyte protoporphyrin IX. Scanty clinical signs are still available. In a third step while clinical findings show a complete features of iron deficiency anemia (weakness, fatigue, palpitations, etc.), laboratory findings show morphologic alterations in red cells (hypochromia and microcytemia), together with the aforementioned disorders in ferrokinetics. Iron deficiency anemia responds very effectively to treatment due a correct etiological diagnosis, crucial to a through therapy tending to first eliminating the causes of it. Prophylaxis against iron deficiency anemia is required in prematurely born and low birth weight infants because of doubled iron requirements. After the second month of life diet is supplemented with 2-4 mg/kg/die of ferrous iron orally along the first year of life.

Adolescent↗