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Biomedical subjects

G Altavilla

Publications and source records attributed to G Altavilla.

At least 73 records · Page 4Linked to original sources

Glycosylation in human colorectal mucosa during tumor development studied by lectins.

The panel of six lectins was used for demonstration of glycosylative changes in the hyperplastic, adenomatous and carcinomatous mucosa of large bowel. The obtained results were rather heterogeneous with regard to lectin binding capacity in the single cases but they proved a certain uniformity of changes inside every tested group. These changes cohered with decrease of capability dysplastic and neoplastic cells to produce of normal goblets and with loss of cell polarity. Possible causes of these alterations are discussed.

Colon↗

Lectin histochemistry of colonic adenomas.

34 adenomas of the colon and adjacent flat mucosa were reexamined by morphological, histochemical and immunohistochemical means. Adenomas were grouped according to the degree of epithelial cell atypia: group 1 (dysplastic adenomas) showing mild and moderate dysplasia and group 2 (cancerous adenoma) with severe dysplasia and carcinoma. Morphological and secretive changes (hyperplasia with hypersialomucin secretion), considered typical of 'transitional mucosa', were constantly found in the adjacent and stalk mucosa. A panel of six lectins were tested using PAP and ABC system methods to compare amount and cytoplasmic localization of labelling sites with the morphological changes such as hyperplasia, dysplasia and carcinoma. All the tested lectins were reactive in up to 90% of adenomas as well as in adjacent mucosa. Positivity was unrelated to the severity of dysplasia and no preferential localization of labelled sites was shown in the adenoma groups. However, cytoplasmic distribution of reactivity was quite different in hyperplastic epithelium compared to dysplastic ones.

Colonic Polyps↗

Co-operation in cell transformation between BK virus and the human c-Harvey-ras oncogene.

Early-passage hamster embryo cells were transformed by recombinant DNA molecules containing BK virus (BKV) early-region gene and either the activated c-Ha-ras oncogene (pBK/c-rasA) or the normal c-Ha-ras proto-oncogene (pBK/c-rasN). The recombinant DNAs had a greater transforming ability and converted hamster cells to a more malignant phenotype than the single genes transfected separately. pBK/c-rasA was significantly more powerful than pBK/c-rasN in conferring to cells all the characteristics of transformation. Transfected DNA sequences were integrated mostly as single insertions into cellular DNA. Specific c-Ha-ras and BKV transcripts as well as c-Ha-ras p21 and BKV T antigen were detected in transformed cells. Although stimulation of c-Ha-ras expression by BKV enhancers cannot be excluded in recombinants, super-transfection and co-transfection experiments in hamster embryo cells and pre-neoplastic cell lines showed that BKV early-region and c-Ha-ras co-operate in transformation by contributing separate and independent functions.

Animals↗

Cooperation in oncogenesis between BK virus early region gene and the activated human c-Harvey ras oncogene.

Rapidly growing, undifferentiated brain tumours were induced in newborn Syrian hamsters by intracerebral inoculation of a recombinant DNA (pBK/c-rasA) carrying the BK virus (BKV) early region gene and the activated human c-Harvey-ras (c-Ha-ras) oncogene. Neither of the two genes inoculated alone nor recombinant DNA of the BKV early region gene and the normal human c-Ha-ras proto-oncogene were tumourigenic. Tumour-derived cell lines propagated in culture were immortalized and had growth characteristics consistent with a fully transformed phenotype. Tumours and tumour cell lines contained pBK/c-rasA sequences integrated into cellular DNA and expressed BKV- and c-Ha-ras-specific transcripts as well as BKV T antigen and c-Ha-ras p21. These findings are discussed in relation to a possible cooperation or synergism between BKV and cellular oncogenes in human neoplasia.

Animals↗

Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial.

From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.

Adult↗

Induction of malignant subcutaneous sarcomas in hamsters by a recombinant DNA containing BK virus early region and the activated human c-Harvey-ras oncogene.

Malignant undifferentiated sarcomas were induced in 11 of 15 (73.3%) newborn Syrian hamsters by s.c. inoculation of a recombinant DNA (pBK/c-rasA) containing BK virus (BKV) early region gene and the activated human c-Harvey-ras(c-Ha-ras) oncogene derived from T24 bladder carcinoma. The two genes inoculated independently as well as a recombinant DNA of BKV early region gene and normal human c-Ha-ras proto-oncogene were not tumorigenic. Tumor-derived cell lines propagated in culture were immortalized and had growth characteristics consistent with a fully transformed phenotype. Tumors and tumor cell lines showed tandem insertions of pBK/c-rasA in high copy number and expressed BKV- and c-Ha-ras-specific transcripts as well as BKV T-antigen and c-Ha-ras protein with a molecular weight of 21,000. We conclude that BKV DNA requires interaction with other oncogenic functions for tumorigenicity. These findings may be relevant to the role of BKV in human neoplasia, where cooperation or synergism between BKV and cellular oncogenes could occur as an aspect of the multifactorial process of carcinogenesis.

Animals↗

[Serum levels of copper and zinc in patients with lung cancer].

Serum copper levels (SCL) and serum zinc levels (SZL) were measured in two groups of lung cancer patients divided according to disease extension. SCL was higher, SZL was lower and SCL/SZL ratio was more raised in patients extensively affected by the disease. It is confirmed that SCL, SZL and the SCL/SZL ratio play an important role in indicating the stage of lung cancer development.

Adult↗

[Behavior of serum sialic acid levels at various stages of neoplastic disease].

Serum sialic acid levels were measured at two different stages of neoplasia (active and non-active phases). CEA levels were also assayed at the same time. 98 patients suffering from different neoplastic diseases and a group of healthy controls were studied. Serum sialic acid levels were always significantly higher in the neoplastic patients. When neoplastic disease were divided into active and non-active groups, it was observed that the level of this glycoprotein was specific in the non-active (NA) phase only for breast tumours and lymphomas. Correlation with CEA levels was also significant in these cases. It is concluded that serum sialic acid assay may be useful only for melanomas, breast tumours and lymphomas where the level of this membrane protein undergoes significant changes according to the stage of the tumour.

Breast Neoplasms↗

Colonic mucosa adjacent to adenomas and hyperplastic polyps--a morphological and histochemical study.

The morphological and histochemical features of colonic mucosa adjacent to 142 adenomas and 31 hyperplastic polyps were studied. Three predominant patterns were identified: (1) normal mucosa, showing normal histological architecture and secretion of sulphomucins; (2) N+ type, histologically normal mucosa with predominance of sialomucins; (3) transitional mucosa; hyperplastic mucosa secreting sialomucins. Hyperplastic changes were observed in the immediate neighbourhood or at the base of adenomas and were more frequent and extensive near large adenomas than around smaller lesions. Sialomucins were often predominant in the mucosa adjacent to large adenomas, but N+ type mucosa was also seen near minute adenomas and hyperplastic polyps and remote from polypoid lesions. Moreover, both hyperplastic and secretory changes were more frequent in the left colon than in the right. These findings seem to suggest that mucosal hyperplasia more likely represents a local change, parallel with or secondary to tumour development rather than a pre-adenomatous lesion. Secretory modifications are widespread and may result from the action of various factors among which carcinogens cannot be excluded.

Adenoma↗

The treatment of recurrent and metastatic cervical carcinoma. Evaluation of an antiblastic combination of methotrexate-adriamycin-bleomycin (MAB).

Thirty patients with local recurrent and/or distant metastatic cervical carcinoma were treated by combined chemotherapy with methotrexate, adriamycin and bleomycin (MAB). Among the 25 evaluable patients 1 CR (4%), 5 PR (20%), 9 SD (36%) and 10 PD (40%) were obtained. A high incidence of cardiotoxicity (20%) and alopecia (32%) was observed. Both phenomena are linked to the anthracyclinic component of the regimen. As the results are not better than those reported by using only methotrexate and bleomycin, the authors did not find it useful to insert adriamycin in this regimen.

Adult↗

Histologic, immunofluorescence, and ultrastructural study of malignant islet-cell tumors of the pancreas induced in hamsters by BK human papovavirus.

Histologic, immunofluorescence and ultrastructural studies were performed in 17 cases of pancreatic carcinomas induced by the BK virus in Syrian hamsters, a unique model of experimentally induced malignant islet cell tumors. The tumors were composed of small, poorly differentiated cells mostly arranged in a trabecular structure. By immunofluorescence all four islet cell types were found in the tumors, though with different frequency. Insulin cells were present in 16 cases, glucagon cells in 11, somatostatin cells in 7, PP cells in 6. Thirteen tumors contained more than one cell type. Insulin cells were the most frequent cell type in 13 cases, and glucagon cells predominated in 1 case. Insulin-containing cells usually occupied a central position within tumor-cell aggregates, while the other cell types were mostly located in a peripheral position, a distribution reminiscent of that seen in normal islets. Gastrin and calcitonin immunoreactivities were not observed. Immunoreactive cells were more abundant in tumors with trabecular structure. Argyrophil cells revealed by the Grimelius method often exceeded the cumulative number of immunoreactive cells in the same tumor, which suggests that there were additional cell types. Multiple cell types were also found in liver metastases. Ultrastructurally most neoplastic cells were poorly granulated. The occurrence of many damaged cells suggests hormone leakage, which may account, at least in part, for the deregulated hormone release from the tumors.

Adenoma, Islet Cell↗

A study of endometrial adenocarcinoma treated with tamoxifen by scanning and transmission electron microscopy.

By scanning and transmission electron microscopy the Authors studied four cases of endometrial adenocarcinoma (stage I, G1) after 15-days treatment with Tamoxifen (20 mg X 2) before surgery. The ultrastructural findings, similar to those observed in untreated adenocarcinomas but quite different from those obtained in MAP-responsive cases - as other Authors reported too - seem to indicate an almost complete absence of secretory or cytotoxic induction at least as far as 15-days treatment is concerned. According to the Authors this study raises many doubts about the usefulness of a first-instance therapeutical protocol based on Tamoxifen alone. However they believe that Tamoxifen can be utilized combined with a progestational agent in a simultaneous or sequence treatment.

Adenocarcinoma↗

Morphologic changes, mucin secretion, carcinoembryonic antigen (CEA) and peanut lectin reactivity in colonic mucosa of patients at high risk for colorectal cancer.

We studied 393 endoscopic colonic biopsies from 72 patients, classified in different groups after assessment of their risk factors, using: histologic, histochemical and immunohistochemical techniques (CEA-PAP and PNA-Px). In high risk patients (Groups A and B) the most relevant modifications were dysplasia with hyposecretion and hyperplasia with sialomucin secretion (TR-type change); in Group A 31 adenomas and 19 hyperplastic polyps also were found. A premalignant nature of dysplasia and predysplastic significance of TR change were suggested: 1) by finding the same alterations in mucosa of Group E (colectomized patients for carcinoma at after 1 year); 2) by increasing expression of CEA and PNA-Px ligands; 3) by their absence in Group D (normal controls). Hyperplastic polyps were confirmed not to be premalignant lesions, but since they had peculiar characteristics (increased CEA and PNA-Px positivity, association with adenomas) it does not seem justified to regard them as lesions unrelated to colorectal cancer, especially when associated with other risk factors. CEA and PNA-Px reactivity correlated well with the risk evaluation and with morphohistochemical changes in the mucosa; the reactivity significantly increased from normal mucosa to dysplasia.

Adenoma↗

[Pathological tolerance to glucose and breast neoplasia].

Thirty non diabetic women with breast cancer and five with benign breast disease have been evaluated by oral glucose tolerance test. 40% showed a diabetic-like curve. The positive women had a metastatic disease. The positive correlation between a pathologic glucose tolerance and the metastatic disease are stressed. The conclusion is drawn that the research of a latent glycidic alteration as monitor of breast cancer evolution is useful.

Adult↗

BK virus-induced tumors in hamsters: a morphological, histochemical and ultrastructural study.

Macroscopic morphology, histology and ultrastructure of BK virus (BKV)-induced hamster and mouse tumors were investigated. Groups of animals were immunosuppressed to study the relationship between immune system and BKV oncogenesis. Ependymomas had the highest incidence, followed by tumors of pancreatic islets, osteosarcomas, lymphomas and sarcomas, sometimes associated in the same animal. All the tumors were found to be BKV specific. Ependymomas showed the shortest latency, infiltrated surrounding tissues but did not metastasize. Pseudo-rosettes were common and basal bodies were observed. Atypia and necrosis were more often present in immunosuppressed animals both for the ependymomas and for the other oncotypes. Pancreatic insulomas were frequently multinodular, possibly because of multifocal origin and metastasized to the liver. Hormone secretory granules were often found on electron microscopy. Osteosarcomas metastasized to lungs and peritoneum and showed the presence of osteoid, chondroblastoid and mixoid areas. Characteristic giant cells were present. Immunosuppression did not enhance tumor incidence and did not influence the latency period. However, neoplastic growth appeared to be more rapid and with more aggressive behavior in immunodepressed animals. These findings suggest an influence of the immune system in tumor development, whereas the virus oncogenic process seems unaffected.

Animals↗