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Biomedical subjects

G Altavilla

Publications and source records attributed to G Altavilla.

At least 19 recordsLinked to original sources
PubMed2002

Hepatosplenic gammadelta T-cell lymphoma presenting with immune-mediated thrombocytopenia and hemolytic anemia (Evans' syndrome).

We describe an unusual case of hepatosplenic T-cell lymphoma in a 61-year-old man who presented with fever, hepatosplenomegaly, anemia, and thrombocytopenia. A spleen biopsy was consistent with T-cell lymphoma. Cytogenetic studies did not reveal chromosome abnormalities. Using the polymerase chain reaction approach, clonality of the T-cell receptor gamma-chain gene rearrangement could be demonstrated, while Southern blot analysis disclosed only a germline configuration of the T-cell receptor beta chain genes. Of interest, an immune-mediated mechanism was demonstrated and was most likely responsible for erythrocyte and platelet destruction; this is, therefore, the first report of gamma T-cell lymphoma in association with Evans' syndrome. Initial steroid treatment was efficacious in limiting autoimmunity but constitutional symptoms did not subside. Chemotherapy (MACOP-B) was successful in obtaining complete clinical remission. Finally, thrombocytopenia in gammadelta T-cell lymphoma patients should be routinely evaluated for platelet autoantibodies.

Anemia, Hemolytic↗
PubMed2000

Enhancement of chemical hepatocarcinogenesis by the HIV-1 tat gene.

The human immunodeficiency virus-1 Tat protein is suspected to be involved in the neoplastic pathology arising in AIDS patients. tat-transgenic (TT) mice, which constitutively express Tat in the liver, develop liver cell dysplasia (LCD) that may represent a preneoplastic lesion. To test if TT mice are predisposed to liver carcinogenesis, we treated them with diethylnitrosamine, a hepatotropic carcinogen. Diethylnitrosamine-treated TT mice developed both preneoplastic and neoplastic lesions in the liver. They showed an enhancement of LCD and developed basophilic liver cell nodules (BLCN), hepatocellular adenomas (HA), and hepatocellular carcinomas (HC). Both preneoplastic (LCD and BLCN) and neoplastic (HA and HC) lesions were significantly more frequent in TT than in control mice: 29.7% versus 12.7% for LCD, 57.9% versus 23.3% for BLCN, 40.6% versus 10.0% for HA, and 50.0% versus 12.7% for HC. These results indicate that Tat expression in the liver predisposes to both initiation of hepatocarcinogenesis and to malignant progression of liver tumors. This study supports a role for Tat in enhancing the effect of endogenous and exogenous carcinogens in human immunodeficiency virus-1-infected patients, thereby contributing to tumorigenesis in the course of AIDS.

Adenoma, Liver Cell↗
PubMed1999

Morphological, histochemical, immunohistochemical, and ultrastructural characterization of tumors and dysplastic and non-neoplastic lesions arising in BK virus/tat transgenic mice.

To study the role in AIDS pathogenesis of the human immunodeficiency virus type 1 (HIV-1) Tat protein, a transactivator of viral and cellular genes, we generated transgenic mice with a recombinant DNA containing BK virus (BKV) early region and the HIV-1 tat gene, directed by its own promoter-enhancer. DNA hybridization revealed that the transgene is stably maintained in all organs of transgenic mice as a tandem insertion in a number of copies ranging from 5 to 20 per cell. In addition, tat and BKV RNA were expressed in all tissues. Transgenic mice developed three types of lesions: 1) tumors, 2) hyperplastic and dysplastic lesions, and 3) non-neoplastic lesions. Tumors of different histotypes, such as lymphomas, adenocarcinomas of skin glands, leiomyosarcomas, skin squamous cell carcinomas, hepatomas, hepatocarcinomas, and cavernous liver hemangiomas, developed in 29% of transgenic animals. The majority of tumors were malignant, invasive, and producing metastases. Conversely, tumors of only two histotypes (lymphomas and adenocarcinomas of skin glands) appeared in control mice. Hyperplastic and dysplastic lesions were more frequent in transgenic than in control mice and involved the skin or its adnexes, the liver and the rectum, indicating multiple targets for the activity of the transgene. Pyelonephritis, frequently complicated with hydronephrosis, inflammatory eye lesions, and amyloid depositions represented the most frequent non-neoplastic lesions detected in transgenic mice. Many of the pathological findings observed in this animal model are comparable to similar lesions appearing in AIDS patients, suggesting a relevant role for Tat in the pathogenesis of such lesions during the course of AIDS.

Adenocarcinoma↗
PubMed1999

Etoposide, l-leucovorin and fluorouracil (ELF) regimen in metastatic gastric cancer: a phase II study.

The role of chemotherapy in metastatic gastric cancer (MGC) is predominantly palliative, therefore regimens with mild toxicity and acceptable activity should be preferred. The combination of etoposide, leucovorin and 5-fluorouracil (ELF) is suitable chemotherapy in this situation. We have enrolled 33 patients with MGC, using the following chemotherapy schedule: l-leucovorin 150 mg/m2 10 minute i.v., followed by etoposide 120 mg/m2 50 minute i.v., followed by 5-fluorouracil 500 mg/m2 10 minute i.v. on days 1-3, every 22 days. All patients are valuable for response, toxicity and survival. Two patients achieved complete response (6%), 10 patients (30%) had a partial response (PR), 9 patients (27%) had stabilization of disease (SD) and 12 patients had disease progression (PD). The median survival for all patients was 6 months (range, 1 to 40+). ELF was well tolerated, the main toxicity being myelosuppression. No toxic deaths occurred. In conclusion, the ELF regimen in our trial demonstrated, in this kind of patient, moderate activity in the absence of relevant toxicity, confirming its suitability in patients in generally poor condition.

Adult↗
PubMed1999

Inactivation of the p16 tumor suppressor gene in adrenocortical tumors.

The mechanisms of adrenocortical tumorigenesis are still unknown. Evidence that the majority of adrenocortical tumors are monoclonal in origin suggests that a progressive accumulation of genetic aberrations, due to activation of protooncogenes and/or inactivation of tumor suppressor genes, leads to abnormal cell proliferation through a multistep process. Inactivation of the p16 tumor suppressor gene (p16INK4A), which encodes the cell cycle protein p16, was investigated in a series of 14 adrenocortical tumors. Using 11 polymorphic microsatellite markers spanning the short arm of chromosome 9, we demonstrated that three of seven adrenocortical carcinomas and one of seven adrenocortical adenomas had loss of heterozygosity (LOH) within chromosome 9p21, the region containing p16NK4A. Immunohistochemistry showed the absence of p16 nuclear staining in all adrenocortical tumors with LOH within 9p21, and positive staining in all remaining tumors without LOH. In conclusion, LOH within 9p21 associated with lack of p16 expression occurs in a considerable proportion of adrenocortical malignant tumors, but is rare in adenomas. Inactivation of p16INK4A may contribute to the deregulation of cell proliferation in this neoplastic disease.

Adrenal Cortex Neoplasms↗
PubMed1999

Focal nodular hyperplasia of the liver associated with portal vein agenesis: a morphological and immunohistochemical study of one case and review of the literature.

Congenital absence of portal vein (CAPV) is a rare malformation. To our knowledge, sixteen cases are reported in western literature. All the cases are associated with other diseases, cardiac malformations (12/17 patients; 16 plus the present case) and hepatic neoplasms being the most frequent observations. We present the case of a girl with a complex malformative syndrome consisting of multicystic kidney dysplasia, CAPV and nodular tumor-like mass of the liver. Angiography showed that the splenic vein and superior mesenteric vein joined to form a common trunk directly entering the inferior vena cava above the liver. A review of the CAPV cases of the literature and the clinical and pathological features of the hepatic lesion, classified as Focal Nodular Hyperplasia (FNH), are extensively discussed.

Abnormalities, Multiple↗
PubMed1998

Carboplatin and teniposide concurrent with radiotherapy in patients with glioblastoma multiforme: a phase II study.

BACKGROUND: The outcome after treatment for glioblastoma remains poor. Therefore, the authors evaluated the long term efficacy and toxicity of treatment with radiotherapy and concurrent carboplatin plus teniposide followed by three cycles of carmustine in patients who underwent resection for glioblastoma. METHODS: Fifty-six newly diagnosed patients with glioblastoma underwent radiotherapy (1.8-2 gray [Gy]/day, 5 days a week using limited fields up to 60 Gy), and concurrent chemotherapy with carboplatin (350 mg/m2) on Days 1, 22, and 43, and teniposide (50 mg/m2) on Days 1, 2, 3, 22, 23, 24, 43, 44, and 45. Four weeks after the end of radiotherapy, patients were given carmustine (200 mg/m2) every 8 weeks for 3 cycles. Treatment then was suspended, but if disease progression was found, treatment was resumed using different drugs. RESULTS: All 56 patients were evaluated for time to progression (TTP) and median survival time (MST). The TTP was 7.5 months and the MST was 12.5 months. Toxicity manifested as thrombocytopenia and in most cases was acceptable. Four patients (7.1%) had radiation necrosis at 2, 2, 7, and 9 months, respectively, from the end of radiotherapy. CONCLUSIONS: The results obtained in the current study with concurrent radiochemotherapy in patients with glioblastoma are comparable to the best results reported using radiotherapy alone followed by chemotherapy with nitrosoureas.

Adult↗
PubMed1998

Congenital absence of the portal vein associated with focal nodular hyperplasia of the liver and cystic dysplasia of the kidney.

Congenital absence of portal vein is a rare malformation. To date, 16 cases have been reported--all in association with other anomalies, i.e. benign or malignant hepatic neoplasms in 6 cases and cardiac malformations in 12. This case report described a girl with congenital absence of portal vein, focal nodular hyperplasia of the liver and cystic kidney dysplasia. Angiography showed the splenic vein and superior mesenteric vein joining to form a common trunk that entered the inferior vena cava directly above the liver. A review of the other cases in the literature is provided and the clinical aspects of our patient are discussed.

Cell Division↗
PubMed1998

Zona fasciculata-like histotype and aldosterone response to upright posture are not related in aldosterone-producing adenomas.

Two distinct subtypes of patients with primary aldosteronism due to aldosterone-producing adenomas (APA), based on different aldosterone responses to angiotensin, have been identified. We evaluated the relationship between adrenal zona fasciculata-like histotype and response of plasma aldosterone to upright posture in a series of patients with APA. Twenty-five patients were retrospectively divided in two groups according to aldosterone response to posture, i.e., a first group without postural change of aldosterone (n = 19) and a second group with at least 30% aldosterone increase after standing (n = 6). The percentage of zona fasciculata-like cells was calculated at histology in all adenoma tissues removed at adrenalectomy. The two groups of patients were similar in sex, age, systolic/diastolic blood pressure, supine/upright plasma renin activity, supine/upright aldosterone, tumor size. No differences between the two groups were observed as to zona fasciculata-like (84 +/- 3% vs 71 +/- 9%, P NS) and non-zona fasciculata-like cells percentage in adenoma tissues. No inverse correlation was found in either group between the percentage change from supine to upright aldosterone and the percentage of zona fasciculata-like cells. Aldosterone and cortisol responses to ACTH testing were similar in the two groups. Our results indicate that the two subtypes of primary aldosteronism based on different postural responses of aldosterone are not due to a different prevalence of zona fasciculata-like histotype in APA.

Adenoma↗
PubMed1998

The value of the prognostic factors in ovarian granulosa cell tumors.

The malignant potential of granulosa cell tumors (GCT) of the ovary is much debated. This study includes 18 patients with a diagnosis of GCT of the ovary. Clinical and pathologic data from patients were compared with flow cytometry ploidy, Ki-67 reactivity and p53 overexpression in order to determine their prognostic usefulness. There was no correlation between ploidy and stages or between ploidy and biological behavior. On the other hand, mitotic count, Ki-67 reactivity and p53 overexpression were associated with stages of disease, recurrent onset and survival. We believe that ploidy, Ki-67 and p53 should be considered important prognostic factors for GCT in association with the other more studied prognostic factors, even if no conclusions can be reached.

Adult↗
PubMed1997

Basaloid squamous cell carcinoma of the larynx and hypopharynx.

Basaloid squamous cell carcinoma (BSCC) is a recently described bimorphic variant of squamous cell carcinoma with distinct morphological and biological features. We describe the clinicopathological findings, along with immunohistochemical and ultrastructural investigations, in 15 new cases of BSCC of the larynx or hypopharynx observed and treated at the otolaryngology department of the University of Padua between 1989 and 1995. The world literature is also reviewed in order to develop a more accurate clinicopathological profile of the tumor. Patient records and histologic slides were reviewed in all of our 15 cases. The patient group consisted of 13 men (86.67%) and 2 women with a mean age of 63.33 years (median 69 years; range 44 to 84 years). Nine patients presented with cervical lymph node metastases. Surgical treatment was the therapy of choice; radiotherapy and chemotherapy have been applied in different combinations. Follow-up was available on all 15 cases. Local recurrence was described in 3 cases. Five of the 9 patients with cervical lymph node metastases developed distant metastases. Distant spread of the tumor without lymph node involvement was observed during follow-up in 4 cases. Nine patients died of disease, 2 are alive with widespread metastases, 2 are alive with no evidence of disease, and 2 have died of other causes. The determined 5-year survival was estimated to be 17.5% by the Kaplan-Meier method. In conclusion, BSCC is a distinctive carcinoma that is important to recognize, because it has a more aggressive biological behavior than conventional squamous cell carcinoma.

Adult↗
PubMed1997

Bleomycin, epirubicin, carboplatin (BECA) in the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck.

The aim of this study was to evaluate three active agents, bleomycin (BLM), epirubicin and carboplatin in a new combination (BECA) in terms of feasibility, activity and toxicity in patients with recurrent and metastatic squamous cell carcinoma of the head and neck. From April 1992 to February 1993 15 pts (12M/3F), median age 53 years, all pretreated (6 surgery + radiotherapy; 3 radiotherapy + chemotherapy; 6 radiotherapy), were treated with BLM 15 mg/m2 days 1-14; epirubicin 30 mg/m2 days 1-14 and carboplatin 300 mg/m2 day 1 every 28 days. In the 14 evaluable pts we observed 1 complete response, CR (7.1%), 4 partial responses, PR (28.6%), 5 stable disease, SD and 4 disease progression, PD with an overall response of 35.7%. The treatment was globally well tolerated, 1 pt with grade 3 leukopenia and 1 pt with grade 3 thrombocytopenia, 1 pt with grade 3 emesis and 1 pt with grade 3 mucositis. At the last follow-up the duration of CR was 34 months, the duration of PRs were respectively 22-10-10-7 months, but the SD ranged from 4 to 6 months. The overall median survival was 8 months (3-36), 14 for responders and 4 for non-responders. This final report seems to confirm the activity and efficacy of the BECA regimen, suitable for outpatient administration with an overall response equal to other more aggressive combinations.

Adult↗
PubMed1997

Cisplatin-gemcitabine combination in advanced non-small-cell lung cancer: a phase II study.

PURPOSE: The nucleoside analog, gemcitabine, has shown activity as a single agent in the treatment of metastatic non-small-cell lung cancer (NSCLC). Its combination with cisplatin in preclinical models suggested synergy between the two drugs. The aim of the study was to evaluate the clinical efficacy and toxicity of the cisplatin-gemcitabine combination in advanced NSCLC. PATIENTS AND METHODS: Forty-eight consecutive previously untreated NSCLC patients entered the trial from January to June 1994. The median age was 60 years (range, 37 to 70) and performance status (PS) was 0 or 1; 22 patients had unresectable stage III disease (21 stage IIIB and one stage IIIA) and 26 had stage IV disease. Gemcitabine 1 g/m2 was administered weekly (days 1, 8, and 15) followed by a 1-week rest and cisplatin 100 mg/m2 on day 2 of each 28-day cycle. Survival and response were determined in accordance with the intention-to-treat principle in all enrolled patients. RESULTS: Of 48 assessable patients, one (stage IV) had a complete response (CR) and 25 achieved a partial response (PR). The overall response rate was 54% (95% confidence interval [CI], 40% to 68%). Thrombocytopenia was the main side effect, with 52% of patients experiencing grade III to IV toxicity, which was usually short-lived and responsible for the omission of gemcitabine administration on day 15 in 50% of chemotherapy courses. The median survival time was 61.5 weeks (95% CI, 40 to 71). CONCLUSION: The combination of gemcitabine and cisplatin induced a high response rate in both stage IIIB and IV NSCLC, with modest side effects. The regimen deserves further careful evaluation in a phase III prospective randomized trial.

Adult↗
PubMed1997

Benign cystic mesothelioma of peritoneum: a case report.

A case of multicystic peritoneal mesothelioma involving the pelvic serosal surface is reported. Morphological and immunohistochemical findings agree with the suggested mesothelial origin of this lesion. Lymphangioma was excluded by the unreactivity to Factor VIII related antigen, ULEX-E1 and CD31. Recurrence after a few months from the first surgical resection disagrees with the reactive hyperplastic nature proposed; a tendency to recur was independent from the absence of an aggressive growth pattern and cytologic atypia.

Adult↗
PubMed1996

Effects of taxol on the human NCI-H295 adrenocortical carcinoma cell line.

We investigated the effects of taxol, an antimicrotubule agent active in different cancers, on the human NCI-H295 steroid-secreting adrenocortical carcinoma cell line. Cells were incubated for 48, 72 or 96 h with taxol 10(-10)-10(-4) M. Cell viability was evaluated by MTT assay with IC50 calculation. Apoptosis was investigated by measuring DNA fragmentation with ELISA assay after cell exposure to taxol at IC50 for 24 h. For secretion studies, aldosterone, cortisol, testosterone and dehydroepiandrosterone-sulphate (DHEA-S) were measured by RIA in the conditioned medium after 96 h exposure to taxol 10(-10)-10(-6) M, and expressed as percentage of steroid production by control cells. By MTT, taxol induced a dose-dependent inhibition of cell proliferation, with ICs50 at 72-96 h corresponding to blood levels achieved in vivo in patients with other types of cancer. Nuclear fragmentation, morphologically confirmed at electron microscopy, showed a 4-fold increase after exposure to taxol. With 10(-6) M taxol, aldosterone decreased to 48%, cortisol to 61%, testosterone to 76% and DHEA-S to 89% of steroid production by control cells. Taxol is an effective cytotoxic and antiproliferative agent in a human adrenocortical steroid-secreting carcinoma cell line. Apoptosis induced by the drug is involved in neoplastic cell death.

Adrenal Cortex Neoplasms↗
PubMed1996

Basaloid squamous cell carcinoma of the head and neck: clinicopathological features and differential diagnosis.

Basaloid squamous cell carcinoma is a recently recognized variant of squamous cell carcinoma. The lesion is histologically distinctive and manifests a predilection for the supraglottis, pyriform sinus, and tongue base. The immunohistochemical profile is discussed. The differential diagnoses include adenoid cystic carcinoma, small cell neuroendocrine carcinoma, basal cell adenocarcinoma, adenosquamous carcinoma, squamous cell carcinoma, spindle cell squamous carcinoma, mucoepidermoid carcinoma, and adenoid squamous cell carcinoma. Basaloid squamous cell carcinoma is a biologically high-grade tumor with a propensity for nodal as well as systemic metastases. It is a morphologic and phenotypic entity with a separate prognostic significance.

Adult↗