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Biomedical subjects

U Tirelli

Publications and source records attributed to U Tirelli.

At least 109 records · Page 6Linked to original sources
PubMed1997

Microsatellite instability in KSHV/HHV-8 positive body-cavity-based lymphoma.

Body-cavity-based lymphoma (BCBL) is a rare non-Hodgkin-'s lymphoma (NHL) type growing in liquid phase in the body cavities. Virtually all BCBL associate with Kaposi's sarcoma-associated herpesvirus/human herpesvirus type-8 infection in the absence of molecular alterations typical of other NHL categories. Microsatellite instability (MSI), a specific variant of genomic instability frequently associated with human cancers, has not been tested in BCBL thus far. In this report, we have analyzed the presence of MSI in the tumor cells of a male patient affected by AIDS-related BCBL. The genomic configuration of 12 distinct microsatellite loci was investigated by polymerase chain reaction amplification of DNA obtained from the patient's tumor cells and from autologous peripheral blood mononuclear cells. MSI was observed at 4/12 microsatellite repeats tested. Absence of the germline allele at one microsatellite locus mapping to chromosome X indicates that, in this BCBL case, MSI represents a clonal genetic lesion affecting virtually all tumor cells. These data suggest that MSI may be potentially involved in the pathogenesis of AIDS-related BCBL.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Malignant tumors and AIDS.

One in six patients with acquired immunodeficiency syndrome (AIDS) both in the USA and Europe develop malignancies, in particular Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL). After an initial rapid increase, the proportion of AIDS patients with KS steadily declined in the USA and in Europe, while the proportion of AIDS-NHL has been stable during the last decade in the USA and Europe. Human immunodeficiency virus (HIV) infected patients are living longer due to advances in antiretroviral therapy and treatment of prophylaxis against opportunistic infections, yet because of their immunodeficiency they are at high risk for cancers, especially NHL. The natural history of cancers in patients with HIV infection differs from that of the general population. Unusual aspects of tumor localization, growth behavior and therapeutical response distinguish tumors in patients with HIV infection from those without. The pathologic and virological aspects of HIV-related tumors are peculiar and a pathological classification of HIV-associated systemic lymphomas based on the morphological features of the two main types, ie, blastic and anaplastic cell lymphomas, has been formulated. The treatment of HIV-related neoplasms is controversial as it is not clear whether conventional therapy, particularly chemotherapy, is able to modify the natural history of these malignancies in the HIV setting. Moreover the treatment of HIV-related tumors presents several problems due to the aggressive behaviors of tumors and because of immunosuppressive chemotherapy employed in patients with immunodeficiency. This paper reviews the most relevant data on the epidemiology, pathology and treatment of malignant tumors in patients with HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1997

Solitary meningeal recurrence in a patient with transitional cell carcinoma of the bladder with locally bulky disease at presentation.

Patients with locally advanced transitional cell carcinoma (TCC) of the bladder are at high risk for systemic relapse, with liver, bone and lung being the commonest sites of metastases. We report the case of a 52-year-old woman with a solitary meningeal relapse, a rare site of recurrence, after 8 months of complete remission obtained with M-VEC for locally advanced TCC of the bladder. We speculate on the likely risk factors related to this unusual site of recurrence.

Carcinoma, Transitional Cell↗
PubMed1997

HIV-associated human herpesvirus 8-positive primary lymphomatous effusions: radiologic findings in six patients.

PURPOSE: To define the imaging features of body cavity-based lymphoma (BCBL) related to the acquired immunodeficiency syndrome. This is a peculiar type of non-Hodgkin lymphoma harboring infection by human herpesvirus 8 (HHV-8) and displaying a peculiar tropism for the serous body cavities. MATERIALS AND METHODS: At diagnosis of BCBL, six consecutive patients were investigated with radiography of the chest and conventional computed tomography (CT) of the chest and abdomen. For all patients, clinical features and results of biologic characterization of the lymphoma were also available. RESULTS: In all patients, chest radiographs displayed bilateral or unilateral pleural effusion in the absence of parenchymal opacities or mediastinal enlargement. CT scans confirmed chest radiographic findings and revealed a slight thickening of the parietal pleura in all patients and a pericardial thickening in four patients. CT also depicted pericardial and abdominal effusions in five and two patients, respectively, in the absence of solid tumor masses or parenchymal abnormalities. CONCLUSION: BCBL must be included among the differential diagnoses of serous effusions detected radiologically in individuals infected with the human immunodeficiency virus (HIV). Since the combination of serous effusion, slight serosal thickening, and absence of solid masses is compatible with, though not specific for, BCBL in the context of HIV infection, radiologic findings need to be complemented by a detailed biologic and virologic characterization of tumor cells.

Adult↗
PubMed1997

Human herpesvirus type-8 (HHV-8) in haematopoietic neoplasia.

Human herpesvirus type-8 (HHV-8) is a lymphotropic herpesvirus originally identified in Kaposi's sarcoma. Among lymphoproliferative disorders, HHV-8 infection is restricted to body-cavity-based lymphoma (BCBL) and multicentric Castleman's disease (MCD). BCBL are B-cell lymphomas growing in liquid phase in the body cavities and most frequently associated with AIDS. BCBL express indeterminate phenotypes, in all cases are associated with HHV-8 infection, and frequently carry Epstein-Barr virus genomes in the absence of c-MYC rearrangements or other genetic lesions characteristic of B-cell lymphomas. The clinical outcome of BCBL is poor with a median survival of only few months. MCD is an atypical lymphoproliferative disorder which displays marked vascular hyperplasia and is commonly associated with Kaposi's sarcoma. HHV-8 infection occurs in 100% of AIDS-related MCD and in approximately 40% of AIDS-unrelated cases. Overall, the consistency of HHV-8 infection in BCBL and MCD, its selectivity throughout the spectrum of lymphoproliferative disorders and the high copy number of HHV-8 DNA sequences in infected cells suggest that the virus plays a pathogenetic role in these disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1997

BCL-6 protein expression in AIDS-related non-Hodgkin's lymphomas: inverse relationship with Epstein-Barr virus-encoded latent membrane protein-1 expression.

This study aimed at investigating the expression of the BCL-6 protein in acquired immune deficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (AIDS-NHLs) and at comparing the expression pattern with the presence of Epstein-Barr virus (EBV) infection of the tumor clone. A total of 34 AIDS-NHL biopsies, including 16 AIDS-related diffuse large-cell lymphomas (AIDS-DLCLs) and 18 AIDS-related small-noncleaved-cell lymphomas (AIDS-SNCCLs) as well as 7 AIDS-SNCCL cell lines were immunostained with a BCL-6-specific monoclonal antibody. Expression of BCL-6 protein was detected in 9 of 16 AIDS-DLCLs, 18 of 18 AIDS-SNCCLs, and 3 of 7 AIDS-SNCCL cell lines. Expression of BCL-6 among AIDS-NHLs occurred independently of the presence of molecular lesions of the bcl-6 gene. Notably, among EBV-positive AIDS-NHL biopsies and cell lines, expression of BCL-6 was mutually exclusive with the expression of EBV-encoded transforming antigen latent membrane protein-1. The mutual exclusion between BCL-6 and latent membrane protein-1 expression was further confirmed by in vitro superinfection experiments of an AIDS-SNCCL cell line originally devoid of EBV sequences. Overall, the frequent association between AIDS-NHLs and expression of BCL-6, a protein selectively expressed by germinal center B cells, suggests that these lymphomas may originate from the germinal center.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The effects of antineoplastic chemotherapy on HIV disease.

Six patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma receiving chemotherapy (CT) with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus granulocyte colony-stimulating factor were sequentially monitored to study the effects of these treatments on their immunologic status (CD4 and CD8 cell counts) and on HIV plasma viremia. We show that mean CD4 cell counts declined significantly after the third cycle of CT (187 +/- 117/microliters before CT versus 92.4 +/- 60/microliters; p = 0.04) and remained significantly reduced 4 months after completion of CT. Modifications of CD8 cell counts were not statistically significant. The effects of CT on plasma viremia, as measured by a competitive polymerase chain reaction technique, were delayed until the fourth cycle, when an increase of viral load ranging from 0.6 to 2 logs (p = 0.027) was observed. After this point, viremia returned to baseline levels, with the exception of two patients who later developed opportunistic infections and one who underwent disease progression. These results suggest that, contrary to CD4 cell counts, plasma viremia could be a faithful surrogate marker for monitoring of HIV disease progression in patients undergoing CT.

Antineoplastic Agents↗
PubMed1996

Combination chemotherapy with doxorubicin, bleomycin, and vindesine for AIDS-related Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma is the most common neoplasm in patients with human immunodeficiency virus (HIV) infection. Although the best therapeutic approach is still unclear, patients with advanced KS are usually treated with systemic chemotherapy. METHODS: A prospective multiinstitutional Italian study evaluated the efficacy and toxicity of combination chemotherapy with doxorubicin, bleomycin, and vindesine (ABVi) in patients with progressive and extensive HIV-related KS. Patients were given doxorubicin, 20 mg/m2 on Day 1; bleomycin, 15 mg on Day 1, and vindesine, 4 mg on Day 1 biweekly +/- granulocyte-colony stimulating factor. RESULTS: Overall, 21 of 38 evaluable patients (55%) achieved an objective response (OR): there was 1 complete response and 20 partial responses. The most important bone marrow toxicity was granulocytopenia in 61% of the evaluable patients; 34% had Grades 3-4 toxicity, according to the World Health Organization Classification. The majority of patients (64%) developed some type of opportunistic infection (OI) during chemotherapy or the follow-up, with cytomegalovirus infection being the most frequent OI observed. The median duration of survival from KS diagnosis and from the start of ABVi therapy was 19 months (range, 3.4-88.5 months) and 9.9 months (range, 0.1-42.4 months), respectively. CONCLUSIONS: The high rate of OI during ABVi chemotherapy and the follow-up is of concern, although these infections possibly could be due to our patients' low CD4+ lymphocyte counts. However, no toxic death was observed in our patients, suggesting that ABVi could be used in patients with aggressive disease, especially those who were previously untreated.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Second-line chemotherapy in human immunodeficiency virus-related non-Hodgkin's lymphoma: evidence of activity of a combination of etoposide, mitoxantrone, and prednimustine in relapsed patients.

BACKGROUND: There is very little experience reported in the literature on the treatment of patients with relapsed or resistant human immunodeficiency virus-related non-Hodgkin's lymphoma (HIV-NHL). We performed a prospective study to evaluate the feasibility and activity of a second-line chemotherapy regimen consisting of etoposide, mitoxantrone, and prednimustine (VMP) in this setting. METHODS: Twenty-one patients were consecutively treated. Thirteen patients were resistant to primary chemotherapy and 8 patients had relapsed after their first complete remission (CR). Etoposide and prednimustine were both given orally at doses of 80 mg/m2 daily for 5 days, and mitoxantrone was given intravenously at a dose of 10 mg/m2 on Day 1; the cycles were repeated every 3 weeks. RESULTS: Nineteen of 21 patients were evaluable for response. The median number of cycles administered was 2 (range, 1-5). A CR occurred in 5 of 19 patients (26%; exact 95% confidence interval; 9-51%). Four of these CRs were observed in the 7 evaluable relapsed patients. Of 45 cycles evaluable for toxicity, severe neutropenia (< 500/microL) occurred in 19 (42%) cycles and severe thrombocytopenia (< 25,000/microL) in 6 (13%) cycles. One toxic death occurred due to sepsis during neutropenia. The overall median survival was 2 months (range, < 1-13 months); the median survival time for the 5 patients with CR (13 months; range, 6-13 months) was statistically significantly longer than that observed in patients without CR (2 months; range, < 1-7 months). CONCLUSIONS: Although the overall prognosis of patients with resistant or relapsed HIV-NHL is very poor, palliative therapy with VMP can be effective and relatively safe in the latter group. Prolonged survival has been observed in some patients who had relapsed after initial chemotherapy.

Adult↗