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Biomedical subjects

A Carbone

Publications and source records attributed to A Carbone.

At least 289 records · Page 16Linked to original sources
PubMed1994

Malignant tumours in patients with HIV infection.

One of the most important though somewhat neglected aspects of research in HIV infection concerns the development, clinicopathological characteristics, and treatment of malignant tumours in infected patients. With the improved survival of patients with AIDS owing to the better prevention and treatment of infectious complications there may well be an increase in AIDS related malignancies. This paper reviews the epidemiology, pathology, and treatment of malignant tumours in patients with HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1994

p53 protein over-expression and p53 gene abnormalities in HIV-1-related non-Hodgkin's lymphomas.

Alteration of the p53 tumor-suppressor gene was studied in non-Hodgkin's lymphomas (NHLs) from HIV-1-infected patients. p53 protein was over-expressed in 10 out of the 45 (22%) cases analyzed, mainly clustering in the small-non-cleaved-cell (SNC) (5/19) and Ki-1+ anaplastic large-cell (ALC) (3/8) sub-types, according to previous findings on HIV-1-unrelated NHLs. p53-positive small-non-cleaved-cell lymphomas presented a diffuse or clustered pattern of p53-positive neoplastic cells consequent upon p53-gene mutations. In contrast, in Ki-1+ ALC lymphomas p53 immunohistochemical reactivity was limited to scattered tumor cells, and no p53-gene alterations could be detected. These results suggest that p53-gene alterations play a role in the lymphomagenetic process of a fraction of HIV-1-related SNC NHLs, however with a frequency no different from that observed in HIV-1-unrelated NHLs of the same sub-type. In HIV-1-related Ki-1+ ALC lymphomas, mechanisms different from gene alterations might be implicated in over-expression of p53 protein.

Base Sequence↗
PubMed1994

Expression of the c-kit receptor in human lymphomas is restricted to Hodgkin's disease and CD30+ anaplastic large cell lymphomas.

The product of the proto-oncogene c-kit is a transmembrane receptor protein that plays an important role in the regulation of normal and neoplastic hematopoiesis via the interaction with its specific ligand termed stem cell factor. To examine whether c-kit product is possibly involved in the pathogenesis of human lymphomas, we analyzed the expression of the c-kit protein in neoplastic cells from a variety of lymphoid tumors by immunostaining of lymph node frozen sections with the 17F11 antibody, detecting an extracellular epitope of the c-kit receptor, and of c-kit RNA by Northern blot hybridization. Of 24 nonHodgkin's lymphomas (NHL) of B- and T-cell phenotype, none expressed immunodetectable c-kit protein that was also not evidenced in lymphoid cells of reactive lymph nodes and normal tonsils. In contrast, c-kit protein was expressed by Reed-Sternberg cells and their mononuclear variants from 11 of 21 Hodgkin's disease (HD) cases, and in tumor cells from 11 of 16 cases of CD30+ anaplastic large cell lymphoma (ALCL). c-kit specific mRNA was also detected in lymph node tissues from HD and ALCL cases but not in neoplastic tissues from NHL other than ALCL. In addition, c-kit/CD30+ tumor cells were evidenced by flow cytometry in a patient displaying massive bone marrow involvement by ALCL. With the exclusion of lymphocyte predominance cases of HD that resulted c-kit expression and the other histologic subtypes of HD or the immunologic phenotype of tumor cells (B, T, nonB-nonT) in both HD and ALCL. The highly restricted expression of the c-kit product among human lymphomas to HD and ALCL provides a further biologic link between these two closely related lymphoma entities.

Hodgkin Disease↗
PubMed1994

Combined antineoplastic and antiretroviral therapy for patients with Hodgkin's disease and human immunodeficiency virus infection. A prospective study of 17 patients. The Italian Cooperative Group on AIDS and Tumors (GICAT).

BACKGROUND: The optimal therapeutic approach for patients with Hodgkin's disease (HD) and human immunodeficiency virus (HIV) infection is unknown. In an attempt to improve the results obtained with standard chemotherapy and to decrease the occurrence of opportunistic infections (OI) during chemotherapy and follow-up observed in a previous experience, the authors designed a prospective combined antineoplastic and antiretroviral approach. METHODS: Between March 1989 and March 1992, 17 consecutive previously untreated patients (median age, 30 years) with HD and HIV infection were enrolled. They had Stage III and IV or Stage I and II disease with adverse prognostic factors. The median CD4+ cell count was 184/microliters. Patients were stratified in two groups and treated accordingly. Group A was made up of patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of less than 3 and without OI. These patients received epirubicin 70 mg/m2 intravenously on day 1, bleomycin 10 mg/m2 IV on day 1, and vinblastine 6 mg/m2 IV on day 1 (regimen EBV). Group B was made up of patients with PS of 3 or greater or previous OI who had received a 50% reduced dose of epirubicin and vinblastine and a full dose of bleomycin. Courses were repeated every 21 days for six cycles. Zidovudine was given at the dose of 500 mg/day from the beginning of chemotherapy in Group B and after the third cycle in Group A. RESULTS: Overall, 14 of 17 (82%) patients had an objective response and 9 of 17 (53%) achieved a complete remission (CR) of disease for a median duration of 20 months. Toxicity was moderate with Grade 3-4 leukopenia in eight patients and Grade 3 thrombocytopenia in one patient. Thirteen of 17 patients received zidovudine as planned with a median duration of 9 months. Only one patient had OI during or after chemotherapy (median follow-up, 11 months). No worsening of HIV markers during the combined therapy was seen, with the median CD4+ cell count before and after therapy being 184/microliters and 203/microliters, respectively. The median survival time was 11 months, with an actuarial survival rate of 48% at 36 months. The median survival time for the nine patients with CR has not been reached at the time of this analysis. CONCLUSIONS: These results revealed the feasibility and the activity of the combination of EBV regimen and zidovudine. Objective response rate seems similar to those previously observed in patients receiving standard chemotherapy, but only one patient had OI, and this compares favorably with the 16 OI observed in 28 patients treated with standard chemotherapy (6% versus 57%) in the authors' previous experience. Thus, it seems that the addition of antiretroviral therapy to the EBV regimen decreased the occurrence of OI during chemotherapy or follow-up.

Adult↗
PubMed1994

Leiomyomatosis with vascular invasion. A unified pathogenesis regarding leiomyoma with vascular microinvasion, benign metastasizing leiomyoma and intravenous leiomyomatosis.

Three uterine leiomyomas with vascular invasion (LWVI), two of which were associated with pulmonary leiomyomatous nodules, and a case of intravenous leiomyomatosis (IVL) invading the vena cava and extending to the right atrium, are described. Despite their histological benignity, these lesions have a strong tendency to metastasize and are closely related to the so-called benign metastasizing leiomyoma (BML). From a clinical point of view, the pulmonary nodules of LWVI are stable or slowly-growing. The IVL was a "worm-like" tumour that presented as a cardiac mass. On the basis of their histological and immunohistological features, a unified histogenetic view of LWVI, IVL and BML of the uterus is proposed. LWVI and BML may be the same pathological entity and microscopic vascular invasion may represent the metastatic mechanism of BML. Alternatively, LWVI may be the initial stage of IVL. In rare instances, IVL may be associated with distant parenchymal (pulmonary) metastases. LWVI seems to be the precursor of both BML and IVL.

Adult↗
PubMed1994

CD26/dipeptidyl peptidase IV expression in human lymphomas is restricted to CD30-positive anaplastic large cell and a subset of T-cell non-Hodgkin's lymphomas.

CD26 is identical to the cell surface ectoenzyme dipeptidyl peptidase IV (DPPIV). CD26/DPPIV is associated with T-cell activation and proliferation and also may function as an auxiliary adhesion factor. Although CD26/DPPIV has been previously studied on lymphoid populations and on leukemias/lymphomas of B- and T-cell phenotype, little is known about its expression and functional role in some specific types of lymphomas, such as CD30-positive anaplastic large cell (ALC) lymphomas and Hodgkin's disease (HD). A series of 81 lymphoma samples, including 23 cases of HD, 17 cases of CD30-positive ALC lymphomas, 41 cases of other non-Hodgkin's lymphomas (NHL), and a panel of HD- or ALC lymphoma-derived human cell lines were evaluated for CD26/DPPIV expression by enzyme histochemistry and immunohistochemistry on frozen sections and cell smears. CD26/DPPIV protein was expressed on neoplastic cells in 12 of 17 (71%) ALC lymphomas irrespective of their antigenic phenotype and in seven of 15 (47%) T-cell NHLs. In contrast, we did not detect CD26/DPPIV expression in tumor cells from 26 cases of B-cell NHL other than ALC lymphomas or in Reed Sternberg (RS) cells and variants of 21 of 23 HD cases. Accordingly, CD26/DPPIV expression was maintained on the CD30-positive ALC lymphoma cell line Karpas 299, but the molecule was not detected on HD-derived cell lines of B, T, or non-B non-T phenotype. These results may support a new potential tool for the phenotypic separation of ALC lymphomas from HD based on the differential expression of the CD26/DPPIV molecule. Moreover, given the demonstration that CD26/DPPIV is identical to the human adenosine deaminase (ADA) binding protein, it could be speculated that CD26/DPPIV also may function by interacting with ADA to regulate the growth of CD26/DPPIV expressing neoplastic cells in ALC lymphomas.

Dipeptidyl Peptidase 4↗
PubMed1994

Multimodal treatment of locally advanced transitional cell bladder carcinoma in elderly patients.

22 patients with locally advanced (T3-T4, M0) transitional cell bladder carcinoma, age greater than 70 years, with medical contraindication or refusal of radical cystectomy, were treated following an ample transurethral resection (TUR), with three chemotherapy cycles. Each cycle consisted of 5-fluorouracil 500 mg/m2 intravenously (i.v.) on days 1 and 8, epirubicin 60 mg/m2 i.v. on day 1 and cisplatin 50 mg/m2 i.v. on day 1. Cycles were repeated every 3 weeks. Subsequently, patients were submitted to a repeat TUR on the area of the initial neoplasm. At computed tomography (CT) scan evaluation, response rate to chemotherapy was 54.5%, with two complete responses. No residual disease (R0) at postchemotherapy TUR was encountered in 8 cases (36%), and microscopic disease (R1) in 4 cases (18%). Median duration of complete responses (R0) was 13.5 months (range 7-57+). Radiation therapy was carried out in 12/14 patients with residual disease at repeat TUR. Overall median duration of response was 10.2 months, while overall actuarial median survival was 11.6 months. Four-year survival was 29%. The approach described was feasible. The chemotherapy regimen employed was not as active as current regimens used in younger patients. The search for more active regimens which are tolerable by the elderly is important.

Aged↗
PubMed1994

High frequency of Epstein-Barr virus latent membrane protein-1 expression in acquired immunodeficiency syndrome-related Ki-1 (CD30)-positive anaplastic large-cell lymphomas. Italian Cooperative Group on AIDS and Tumors.

Immunohistochemical detection of Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP-1) was used to identify EBV-associated Ki-1-positive anaplastic large-cell (ALC) lymphomas occurring in 11 patients with and 29 patients without human immunodeficiency virus (HIV) infection. In addition, 18 representative cases of other acquired immunodeficiency syndrome (AIDS)-related lymphomas and 66 cases of Hodgkin's disease, including 14 patients with HIV infection, were investigated. In patients with HIV infection, LMP-1 was found more frequently in Ki-1-positive ALC lymphomas than in other histotypes, although the difference in EBV association between Ki-1-positive ALC and other lymphomas was not significant. In these patients, the percentage of LMP-1 expressing Ki-1-positive ALC lymphomas was significantly higher than that found in patients without HIV infection (72.7% vs. 24.1%; P < .01), thus suggesting an etiologic role for EBV in a large proportion of AIDS-related Ki-1-positive ALC lymphomas. Moreover, the frequency of LMP-1 expression in Hodgkin's disease cases (71.4% in patients with and 21.1% in patients without HIV infection) was close to that found in Ki-1-positive ALC lymphoma cases, supporting the view that the higher frequency of EBV association with both entities detected in patients with HIV infection may be AIDS-related.

Humans↗
PubMed1994

Cost-benefit of granulocyte colony-stimulating factor administration in older patients with non-Hodgkin's lymphoma treated with combination chemotherapy.

BACKGROUND: Older patients with non-Hodgkin's lymphoma (NHL) display a poorer response to chemotherapy and a significantly higher treatment-associated toxicity than do younger individuals. We investigated the potential clinical benefits and the cost-effectiveness of accelerated granulocyte recovery induced by recombinant granulocyte colony-stimulating factor (G-CSF) in patients with aggressive NHLs, aged 60-70 years, during treatment with a second-generation combination chemotherapy. PATIENTS AND METHODS: 12 consecutive patients (median age 66 years) treated with six to eight courses of CHVmP/VB plus subcutaneous G-CSF (5 micrograms/kg/day) were compared with 11 consecutive subjects (median age 65 years) who received the same chemotherapy regimen without growth factor support. The two groups of patients were fully comparable as to the clinicopathologic features. A comparative analysis of treatment costs (including hospitalization, antimicrobial prophylaxis and therapy, supportive and diagnostic procedures, and G-CSF) was also performed. RESULTS: Both the overall response rate and the percentage of complete remissions were comparable in the two treatment groups. In the control group, 32.5% of chemotherapy courses were delayed, as opposed to 19% in the G-CSF group (p = 0.05). The mean duration of delay for patients receiving or not receiving G-CSF was 10.1 and 25.9 days, respectively (p = 0.02). Grade 3 and 4 granulocytopenia complicated 27.7% of chemotherapy courses in control patients and only 4.8% in subjects receiving G-CSF (p < 0.001). Similarly, severe infections and mucositis were significantly higher in patients receiving chemotherapy alone (15.6% and 3.6%, respectively) compared to the G-CSF group (4.8%, p = 0.01; p = 0.04, respectively). A mean of 1.1 days/course of hospitalization was required in the control group, as opposed to 0.2 days/course in patients receiving G-CSF (p = 0.05). Although overall treatment costs were higher in the control group, single cost of the recombinant growth factor exceeded by far all the other expenses in the G-CSF group, reaching a statistical relevance (p = 0.01). CONCLUSIONS: The inclusion of prophylactic G-CSF in the treatment plan for aggressive NHL in older patients appears safe and cost-effective in view of the peculiar clinical features of aged subjects and the possibility of delivering effective doses of antineoplastic drugs on an outpatient setting.

Age Factors↗
PubMed1994

Hodgkin's disease in patients with HIV infection and in the general population: comparison of clinicopathological features and survival.

BACKGROUND: Hodgkin's disease (HD) has been described in patients with HIV infection in association with unfavourable prognostic factors. Similarly, HD in the older general population has a poorer prognosis than in younger patients. PATIENTS AND METHODS: With the aim of comparing the clinicopathological features and survival of HD in HIV-infected patients and in the general population, we analysed 176 patients with HD from 1986 to 1992. We divided the 84 HIV-negative patients into two groups: group A included patients less than 55 years old, group B patients of 55 years or older. This division was made in order to compare HD in HIV-infected patients with the less favourable group of patients with HD in the general population, i.e., older patients. RESULTS: Patients of the older group and HIV-infected patients had a significantly lower frequency (31% and 21%, respectively) of nodular sclerosis subtype compared to the younger group (85%). Mixed cellularity (MC) is significantly more frequent both in the older group and in HIV-infected patients. Lymphocyte predominance is more frequent (16%) in older patients than in the other two groups. HIV-infected patients are more likely to show advanced stages, B symptoms, and extranodal involvement. Chemotherapy (CT) alone has been the most widely used (83%) treatment in HIV-infected patients, while CT plus radiotherapy (RT) has been mostly employed in the general population. Twelve (14%) HIV-infected patients did not receive any treatment. Complete remission was achieved in 51% of the cases in the HIV-infected patients, and around 90% of the cases in the general population. The estimated 4-year survival rate in the HIV-infected patients is much lower (33%) than in the other two groups (100% in group A, and 88% in group B). CONCLUSION: While MC is the most common histological subtype both in HIV-infected patients and in the older general population, HD in HIV-infected patients has a worse prognosis than in the older general population, not only because of underlying HIV infection, but also because of the more unfavourable clinicopathological features at presentation.

Actuarial Analysis↗
PubMed1994

Human herpesvirus 6: a survey of presence and variant distribution in normal peripheral lymphocytes and lymphoproliferative disorders.

The presence and distribution of human herpesvirus 6 (HHV-6) variants was investigated by polymerase chain reaction in samples from healthy donors and biopsies from non-Hodgkin's lymphomas and Hodgkin's disease. HHV-6 DNA was present in peripheral blood lymphocytes of 17% of healthy donors, variant B three times more frequently than A. HHV-6 was not present in 35 non-Hodgkin's lymphomas of B cell origin and was in only 1 of 10 non-Hodgkin's lymphomas in AIDS patients. HHV-6 DNA was present in 29% of Hodgkin's disease samples; variant B was more frequent than A. Epstein-Barr virus DNA was detected in 38% of Hodgkin's disease biopsies and did not correlate with HHV-6. Thus, the two HHV-6 variants are differently distributed in the healthy population, and the virus probably has no direct role in the development of B cell non-Hodgkin's lymphoma. The detection of HHV-6 DNA in about one-third of Hodgkin's disease biopsies suggests that HHV-6 might be associated with a subset of this disorder.

DNA, Viral↗
PubMed1994

The aged patient with lung cancer. Management recommendations.

Elderly patients with lung cancer have not benefited from the therapeutic improvements obtained during the 1980s with younger adults. Potentially operable non-small-cell lung cancers are more common in elderly patients, who are more likely to have localized disease at diagnosis. Even so, elderly patients are rarely treated with surgery. Radiotherapy remains the most frequently adopted tool to treat non-small-cell lung cancer in this age group. Epipodophyllotoxin derivatives constitute the best option for chemotherapy of elderly patients with small-cell lung cancer. When used as single agent regimens, these drugs show the same overall response rate as combination chemotherapy, but with reduced toxicity. Haematopoietic growth factors are used to reduce bone marrow damage following cytotoxic chemotherapy, and may be a promising tool in elderly patients. Special attention should be given to increasing the number of elderly patients with small-cell lung cancer enrolled in phase I and II studies to investigate new agents for the treatment of this tumour.

Aged↗
PubMed1994

[Cytogenetic analysis in the definition and classification of non-Hodgkin's lymphomas].

Cytogenetic analysis of Non-Hodgkin's Lymphomas (NHL) taken together with immunophenotypic and genotypic studies, may contribute to better define their morphologic classification. In this review the main cytogenetic data have been summarized, looking at a histopathologic NHL categorization that is related to a modern multiparametric approach. The correlation of non random chromosome abnormalities with NHL categories will augment information about their pathogenesis and tumor progression.

Aneuploidy↗