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Biomedical subjects

A Carbone

Publications and source records attributed to A Carbone.

At least 235 records · Page 13Linked to original sources
PubMed1996

Hodgkin's disease: old and recent clinical concepts.

The diagnosis of Hodgkin's disease (HD) is still primarily based on the histopathologic criteria presented by Lukes et al in 1965. Over the past three decades, however, advances in immunohistochemistry, molecular studies, and virologic findings have provided evidence that HD exhibits significant heterogeneity. Whereas the nodular sclerosis subtype is the major subset of the "classic" disease, it has become evident that the nodular, lymphocytic predominance subtype may represent a minor distinct subset, and possibly a distinct disease entity. Furthermore, there is strong evidence that the mixed cellularity subtype may be an Epstein-Barr virus-related disorder. Finally, based on phenotypic and genotypic features, the existence of a "continuum" between a fraction of HD cases, including the lymphocytic depletion subtype, and CD30-positive anaplastic large cell lymphomas has been suggested.

HIV Infections↗
PubMed1996

Age and serum lactate dehydrogenase level are independent prognostic factors in human immunodeficiency virus-related non-Hodgkin's lymphomas: a single-institute study of 96 patients.

PURPOSE: The role of classical pragnostic factors (ie, age, performance status [PS], stage, extranodal involvement, and serum lactate dehydrogenase [LDH] level) included in the International Index for diffuse large-cell non-Hodgkin's lymphoma (NHL) of the general population is presently unknown in the setting of human immunodeficiency virus (HIV). To assess the prognostic value of these factors in HIV-related NHL, we reviewed the cohort of patients with HIV-related NHL diagnosed and treated with combination chemotherapy (CT) at our institution. PATIENTS AND METHODS: Ninety-six patients with systemic HIV-related NHL diagnosed and treated with combination CT regimens between September 1987 and December 1993 at the Centro di Riferimento Oncologico, Aviano, Italy, were studied. All clinical and laboratory data were evaluated by univariate and multivariate analyses, using overall survival as the end point. RESULTS: Complete remission (CR) occurred in 48% of patients; the overall median survival and disease-free survival times were 7 and 13 months, respectively. Among the classical and HIV-related prognostic factors, the following had a statistically significant influence on survival: PS > or = 2, elevated LDH level, age greater than 40 years, a CD4 cell count less than 100/microL, active opportunistic infections at diagnosis of NHL, and B symptoms. Multivariate analyses showed that only age, serum LDH level, and CD4 cell count were independent predictors of shortened survival. The increased hazard for patients greater than 40 years of age was 1.6 (95% confidence interval [CI], 1.2 to 2.3), for patients with increased LDH it was 1.8 (95% CI, 1.01 to 3.1), and for patients with a CD4 cell count less than 100/microL it was 1.7 (95% CI, 1.01 to 2.9). CONCLUSIONS: Our study shows that in addition to HIV-related prognostic factors, ie, CD4 cell count less than 100/microL, classical prognostic factors such as age and serum LDH level are independent prognostic factors and should be included in the design of future clinical trials of HIV-related NHL.

Adult↗
PubMed1996

Atrial natriuretic factor (ANF) and ANF receptor C gene expression and localization in the respiratory system: effects induced by hypoxia and hemodynamic overload.

Atrial natriuretic factor (ANF) and ANF receptor C (ANF.RC) expression have been investigated in healthy and cardiomyopathic hamsters (CMPH) with widespread necrosis of the diaphragm and myocardium leading to respiratory and heart failure. ANF- and ANF.RC-producing cells were localized in different structures of the respiratory system, and the regulation of their expression by the individual and/or combined action of hypoxia and hemodynamic overload was analyzed. The study was performed in 20-, 90-, and 150-day-old animals using immunohistochemistry, in situ hybridization, Northern blot, and RIA analyses. ANF was shown to be expressed in the tracheo-bronchial epithelium and muscle and, to a lesser extent, in the alveolar wall and muscular media of the pulmonary arteries and extraparenchymal pulmonary veins in both healthy hamsters and CMPH. In 150-day-old CMPH, hypoxia (PaO2 < 50 mm Hg) induced a 10-fold increase in ANF messenger RNA accumulation and a 6-fold increase in the immunoreactive ANF (IR-ANF) concentration in lungs, as quantitated by RIA. As plasma IR-ANF concentrations were elevated in all CMPH age groups, it was most likely produced by the myocardium. ANF.RC messenger RNA was homogeneously distributed throughout the entire respiratory system and was increased 2-fold in hypoxic 150-day-old CMPH only. These results suggest that ANF originating in the respiratory system exerts only paracrine effects on different structures of the respiratory system in addition to the action of circulating ANF. Hemodynamic overload (left ventricular end-diastolic pressure, 17.20 +/- 3.80 mm Hg) might contribute to enhanced ANF gene expression only in extraparenchymal pulmonary vein walls of 150-day-old CMPH. We also propose that ANF.RC overexpression might be a protective mechanism operated via either ANF clearance or inhibition of adenylate cyclase activity to counteract exaggerated smooth muscle relaxation.

Animals↗
PubMed1996

Malignant lymphomas in patients with HIV infection.

During the last two decades, the occurrence of non-Hodgkin's lymphoma (NHLs) has been increasing both in the general population, in which their incidence doubled, and in people with human immunodeficiency virus (HIV) infection, in whom a 100-fold increase has been observed since the onset of the AIDS epidemic. HIV infected patients are living longer owing to advances in antiretroviral therapy and treatment of prophylaxis against opportunistic infections but because of their immunodeficiency they are at high risk of 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 behaviour and therapeutical response, distinguish tumors in patients with from those without HIV infection. 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, i.e. blastic and anaplastic cell lymphomas has been formulated. The treatment of HIV-related neoplasms is controversial as it is not clear whether conventional therapy and in particular chemotherapy is able to modify the natural history of these malignancies in HIV setting. Moreover the treatment of HIV-related tumors presents several problems, due to the aggressive behaviours of tumors and because of immunosuppressive chemotherapy employed in patients with immunodeficiency.

Humans↗
PubMed1996

Association of 6q deletions with AIDS-related diffuse large cell lymphoma.

Deletions of chromosome 6 at band q27 represent the site of a putative novel tumor suppressor gene in non-Hodgkin's lymphomas (NHL) of the immunocompetent host. Although several genetic lesions have been identified in AIDS-related NHL (AIDS-NHL), the involvement of 6q27 loss has not been investigated in this NHL category. In this report, we tested the presence of a 6q deletion at the molecular level in a panel of AIDS-NHL representative of the major histologic types, including AIDS-related small non-cleaved cell lymphoma (AIDS-SNCCL; n = 10), AIDS-related diffuse large cell lymphoma (AIDS-DLCL; n = 13) and AIDS-related anaplastic large cell lymphoma (AIDS-ALCL; n = 3). We report that 6q deletions occur in 5/26 AIDS-NHL tested (19.2%). Notably, 6q deletions do not randomly distribute throughout the spectrum of AIDS-NHL histologic types, but rather selectively cluster with AIDS-DLCL (5/13; 38.4%). Overall, these data add to the notion that the molecular pathogenesis of AIDS-NHL is heterogeneous and that distinct genetic pathways associate with specific histologic categories of AIDS-NHL.

Blotting, Southern↗
PubMed1996

CD30 ligand expression in nonmalignant and Hodgkin's disease-involved lymphoid tissues.

The CD30 ligand (CD30L) is a type II transmembrane glycoprotein of the tumor necrosis factor ligand superfamily. Recent cloning of CD30L has enabled studies to explore its function and tissue distribution. For instance, recombinant CD30L has been shown to co-stimulate T cells and to act as mitogen for Hodgkin's disease (HD)-derived cell lines. The counter-receptor for CD30L, ie, CD30, is a type I cytokine receptor that is highly expressed by activated T cells, Hodgkin and Reed-Sternberg (H-RS) cells, and anaplastic large cell lymphoma cells. In the present study, recombinant membrane-bound and soluble human CD30L were instrumental to raise a monoclonal antibody (M80) recognizing membrane-bound CD30L on transfected and native cells. With this reagent, a panel of cultured lymphoma-derived cell lines as well as primary normal, reactive, and HD-involved lymphoid tissues were examined for expression of CD30L by immunostaining and flow cytometry. In reactive lymphnodes and tonsils, CD30L was expressed by a small subset of lymphoid cells, histiocytes, and granulocytes. Higher levels of CD30L expression were noted in HD lesions among bystander cells; ie, T cells and granulocytes that surrounded H-RS cells. Native CD30L displayed at the cell surface was functionally active as shown by the ability of fixed granulocytes to interact with CD30+ cell lines. Moreover, CD30L was detectable, although to a lower staining intensity, in primary H-RS cells of all HD tissues investigated regardless of the histological subtype and the phenotype of H-RS cells (ie, CD30+/CD40+ versus CD30-/CD40+). Co-expression of CD30 and CD30L that was seen on H-RS cells of all, except the CD30- nodular lymphocyte predominant, subtypes of HD may point to the use of this pair of molecules in paracrine and/or autocrine mitogenic cell interactions. Monoclonal antibody M80 may thus represent a useful tool for studying CD30L expression on cultured cell lines and primary cells from normal, reactive, and malignant tissues.

Antibodies, Monoclonal↗
PubMed1996

Three consecutive cases of adenomatoid tumour of the epididymis: histological considerations and therapeutical implications. Review of the literature.

Adenomatoid tumour is an uncommon neoplasm of the male genital tract. The Authors report their recent observation of three consecutive cases of adenomatoi tumour of the epididymis. In all cases the diagnosis was difficult and done only by an accurate histological examination. The treatment was conservative, consisting in the removal of the neoplasm. After a follow up of at least two years the patients do not show any sign of relapses confirming the validity of the surgical therapeutical approach performed. Because of the unfrequent observation of these forms and the difficulty in the diagnosis, the Authors stress the necessity of the surgical exploration with an accurate microscopic examination of the specimens. Moreover a review of the literature from a histological and therapeutical point of view was done and reported.

Adenomatoid Tumor↗
PubMed1996

The role of current and new discriminating markers in the immunodiagnosis of Hodgkin's disease and other phenotypically related lymphomas.

Recent data have shown that CD40 antigen and its ligand (CD40L), and the CD26 molecule are differentially expressed among Hodgkin's disease (HD) (CD40+, CD26, CD40L), peripheral T-cell (PTCL) (CD40L+/-, CD40, CD26) and CD30 positive anaplastic large cell (ALC) (CD26+, CD40L) lymphomas. Since CD40 molecule is consistently detected on Reed-Sternberg (RS) cells and their morphologic variants with a distinctive staining pattern. CD40 expression provides a new potential tool for the identification of RS cells of HD in fixed and paraffin-embedded material. Furthermore, the combined application of anti-CD40 and anti-CD26 MoAbs may discriminate HD from morphologically and immunophenotypically related ALC lymphomas. In fact a CD26+/CD40 profile is restricted to CD30 positive ALC lymphomas. Finally, the combined application of anti-CD40 and anti-CD40L MoAbs provides additional significant features in differentiating HD from PTCL due to the constant expression of CD40+/CD40L phenotype in HD and its absence in PTCL, which in turn express CD40/CD40L+/- phenotype.

Antigens, CD↗
PubMed1995

The expression of CD26 and CD40 ligand is mutually exclusive in human T-cell non-Hodgkin's lymphomas/leukemias.

CD26 and CD40 ligand (CD40L) are surface molecules on human activated T lymphocytes that play a critical role in the regulation of lymphopoiesis. Both molecules are expressed on a restricted fraction of human T-cell non-Hodgkin's lymphomas (NHL)/leukemias; however, little is known about their functional and/or clinical significance in these disorders. In this study, the pattern of expression of CD40L was compared with that of the CD26 molecule. A series of 67 human T-cell NHL/leukemias and a panel of leukemia/lymphoma T-cell lines were evaluated by immunohistochemistry, flow cytometry, and RNA studies. The overall frequency of CD26+ and CD40L+ samples was rather similar (25/67 [37%] v 18/67 [27%]). However, the majority of CD26-expressing cases clustered in the lymphoblastic lymphomas (LBL)/T-acute lymphoblastic leukemias (ALL; 12/23) and CD30+ anaplastic large-cell (ALC) lymphomas (5/8), whereas CD40L+ lymphomas included a large fraction of mycosis fungoides (11/21 [52%]). CD26 and CD40L coexpression was found only in 2 myocosis fungoides cases and 1 small lymphocytic lymphoma. Thus, the expression of the two antigens was mutually exclusive in almost all T-cell lymphomas/leukemias. Accordingly, lymphoma cell lines expressed either one of the molecules or the relative amounts of CD26 and CD40L were inversely proportional. In contrast, reactive T lymphocytes from patients with non-neoplastic T-cell expansions and in vitro activated CD3+ or CD4+ normal T cells were found to coexpress CD40L and CD26. Results of a multivariate analysis showed that the expression of CD26 in T-cell LBL/ALL patients was associated to a worse outcome in terms of survival, as compared with patients with CD26- tumors (P < or = .0001). Based on our results, it can be concluded that, (1) as opposed to activated or reactive normal T cells, the expression of CD26 and of CD40L is mutually exclusive in human T-cell lymphomas/leukemias; (2) expression of CD26 is restricted to aggressive pathologic entities, such as T-cell LBL/ALL and T-cell CD30+ ALC lymphomas, whereas CD40L is expressed on slow progressing diseases such as mycosis fungoides; and (3) within the T-cell LBL/ALL group of tumors, CD26 may identify a subset of poor prognosis patients.

Adolescent↗
PubMed1995

Characteristics of EBV-infected cells in HIV-related lymphadenopathy: implications for the pathogenesis of EBV-associated and EBV-unrelated lymphomas of HIV-seropositive individuals.

The present study was performed with the aim of better defining the possible role of Epstein-Barr-virus (EBV)-infected cells in the pathogenesis of HIV-related lymphadenopathy syndrome (LAS). In addition, since LAS has been considered as a pre-lymphomatous lesion, we also wished to elucidate the possible contribution of EBV-carrying cells present in LAS tissues to the development of HIV-associated malignant lymphomas. To this end, we have characterized EBV-infected cells in LAS lymph nodes in terms of EBV DNA prevalence, tissue distribution in relation to HIV-carrying cells, virus sub-type, expression of latent and replicative antigens, and presence of clonal EBV episomes. When compared with HIV-unrelated lymphadenopathies (4/10, 40%), LAS showed a higher prevalence of EBV DNA (14/20, 70%). Comparable values of EBV prevalence were detected in LAS with follicular hyperplasia (12/16, 75%) and with follicular involution (4/4, 100%). All EBV+ non-neoplastic lymph nodes from HIV-seronegative patients carried type-I EBV, whereas LAS specimens showed almost equivalent distribution of the 2 EBV sub-types. Of the 14 EBV-carrying LAS, 4 (29%) were positive by Southern-blot analysis for the BamHI-W region of the virus genome but negative for the presence of monoclonal EBV episomes. In situ hybridization revealed a remarkably higher load of EBV-infected cells in LAS than in HIV-unrelated lymphadenopathies. In LAS lymph nodes, EBV-carrying cells were identified as isolated, cytologically normal elements, sometimes with immunoblastic morphology, usually scattered throughout the interfollicular areas. By contrast, the expression of HIV p24 was restricted to germinal center cells. All the EBV+ LAS samples were negative for the expression of EBV-encoded latent (LMP-1 and EBNA-2) and replicative proteins (BZLF-1, BHLF-1, EA-D, EA-R and VCA). In addition, amplification of the immunoglobulin heavy-chain genes using 2 different polymerase-chain-reaction protocols showed evidence of B-cell clonal expansion in 2/20 (10%) LAS, one EBV- case, and one sample with low numbers of EBV-infected cells. These results suggest that (i) EBV-carrying cells are probably not involved in the development of LAS, either directly or indirectly; (ii) type-2-EBV-infected cells are present in LAS lymph nodes from the early phases of HIV infection; (iii) EBV-carrying LAS per se probably does not constitute a lesion at high risk for subsequent development of EBV+ lymphomas; (iv) it is unlikely that a high viral load or strong EBV-mediated antigenic stimulation plays a contributory role in the development of EBV-unrelated lymphomas of HIV-seropositive individuals.

AIDS-Related Complex↗
PubMed1995

Hepatitis C virus within a malignant lymphoma lesion in the course of type II mixed cryoglobulinemia.

Hepatitis C virus (HCV) has been implicated as the major etiologic factor sustaining B-cell clonal expansion in type II mixed cryoglobulinemia (MC). A putative pathogenetic role of HCV in the development of MC-associated B-cell malignancies has also been speculated. We report for the first time the localization of HCV within a parotid non-Hodgkin's lymphoma (NHL) lesion in the course of HCV-related type II essential MC, an important step to implicate any infectious agent in the lymphomagenesis. Plus and minus strand HCV RNA was first demonstrated by polymerase chain reaction on the whole RNA from the lesion. Further immunohistochemical studies localized HCV c22 proteins in the residual ductal or acinar parotid structures, which also abnormally expressed HLA-DR antigens. Weak c22 signals were inconstantly detected in cells strictly confined around the residual epithelium, while all the remaining infiltrating cells in the parotid lesion stained c-22-negative. Staining for c33 and c100 HCV antigens was negative. In situ hybridization (ISH) studies again identified the residual parotid epithelial cells as the site of HCV infection and replication in the NHL lesion. Sialotropic viruses previously involved in lymphoproliferation, ie, Epstein-Barr virus and human herpesvirus-6, were absent in the same tissue lesion. According to the current models of B-cell lymphomagenesis, a role of HCV as an exogenous antigenic stimulus should be considered for NHL development in the present case, whereas malignant B cells do not appear permissive of active HCV replication. Further efforts would be worthwhile to clarify a role of HCV infection in the development of some B-cell malignancies.

Aged↗
PubMed1995

Local suppression of Epstein-Barr virus (EBV)-specific cytotoxicity in biopsies of EBV-positive Hodgkin's disease.

Epstein-Barr virus (EBV)-positive Hodgkin's and Reed-Sternberg (HRS) cells express the virus-encoded latent membrane proteins LMP1 and LMP2 that could serve as rejection targets in Hodgkin's disease (HD). To examine whether EBV-triggered reactivities can be detected in the tumor, we have compared cytokine mRNA expression, cell phenotype, and cytotoxic activity in biopsies from 8 EBV-carrying and 6 EBV-HD patients. Neither the pattern of lymphokine production nor the cell phenotype of the in vivo-activated interleukin-2-responding populations provided a clear discrimination between EBV+ and EBV- cases. HLA class I-restricted EBV-specific cytotoxicity was shown in interleukin-2-dependent cultures from 3 of 3 EBV- tumors, whereas cultures from 6 of 6 EBV+ tumors were either noncytotoxic or exerted LAK-type cytotoxicity. EBV-specific cytotoxic T lymphocyte precursors were present in the blood of 1 patient carrying an EBV+ tumor. The results suggest that a tumor-associated suppression of EBV-specific T-cell responses may play an important role in the pathogenesis of EBV+ HD.

Adult↗
PubMed1995

Suppressive role of the metastasis-related nm23-H1 gene in human ovarian carcinomas: association of high messenger RNA expression with lack of lymph node metastasis.

The nm23-H1 gene has been proposed as a metastasis suppressor gene. It is located on the long arm of chromosome 17, which is frequently deleted in ovarian cancer, and shows altered expression and structure in some advanced neoplasms. To evaluate the role of nm23-H1 in ovarian carcinogenesis, we have analyzed this gene in 66 primary human ovarian carcinomas at both the DNA and RNA levels. Despite the high frequency (76%) of nm23-H1 loss of heterozygosity (LOH), the complete absence of gene mutations in the coding portions of the retained allele clearly indicated that, in ovarian carcinomas, this gene does not function in the same way as do classic oncosuppressor genes. The relationship of clinicopathological parameters with nm23-H1 gene deletions and expression levels was also investigated. LOHs were more common in the serous and endometrioid histotypes (85 and 93%, respectively), and the highest LOH frequency was detected in poorly differentiated tumors (89%). A significant relationship between nm23-H1 mRNA expression and lymph node metastasis was observed in high-grade tumors, which are intrinsically more invasive than are low-grade tumors. In particular, among the poorly differentiated tumors showing areas of undifferentiated solid carcinoma (classified as G3/G4), lymph node-negative tumors displayed expression levels that were significantly higher than those of lymph node-positive tumors (P < 0.001). In conclusion, our data suggest that the nm23-H1 gene product may exert an inhibitory effect on the lymphatic dissemination of human ovarian tumors. However, several other factors, biological or time and patient dependent, influence the complex metastatic progression of ovarian tumors and may cooperate with nm23-H1 in the promotion or inhibition of this process.

Adenocarcinoma↗
PubMed1995

MDM2 overexpression does not account for stabilization of wild-type p53 protein in non-Hodgkin's lymphomas.

p53 protein overexpression is a frequent finding in non-Hodgkin's lymphomas (NHL), being detected in over 25% of the cases. Moreover, some high-grade lymphomas and a large fraction of low-grade tumors show a pattern of scattered p53 accumulation in a limited percentage of neoplastic cells. In contrast, NHLs show a low frequency of p53 gene mutations. To investigate the molecular bases of p53 protein overexpression, a large series of NHLs was analyzed for p53 gene status. The analysis of the entire coding region of the gene (exons 2-11) and corresponding donor and acceptor splicing sites indicated that a significant proportion of p53-positive tumors overexpresses a wild-type form of p53 protein (wt-p53). To assess whether wt-p53 accumulation was related to the formation of inactive complexes with endogenous proteins, MDM2 oncogene expression and amplification were analyzed. MDM2 overexpression was detected only in one third of the wt-p53-positive cases, thus excluding that MDM2 accounts tout court for the accumulation of a normal p53 protein. However, the fact that MDM2 overexpression was detected in only the p53-positive cases and the observation that MDM2-positive cells were a subpopulation of p53-positive cells suggest a link between the two phenomena. In particular, our results indicate that the accumulation of a wt form of p53 protein could promote the overexpression of the MDM2 gene product. In addition, the prevalence of MDM2 positivity in intermediate/high-grade tumors together with the concordant expression of wt-p53 and MDM2 only in the high-grade component of a 'composite' lymphoma suggests that perturbation in the MDM2/p53 critical ratio could play a role in lymphoma progression.

Base Sequence↗
PubMed1995

High frequency of EBV association with non-random abnormalities of the chromosome region 1q21-25 in AIDS-related Burkitt's lymphoma-derived cell lines.

Chromosome 1q abnormalities represent the second most frequent cytogenetic lesion of Burkitt lymphoma (BL) and acute lymphoblastic leukemia (ALL)-L3. The most frequent change is partial duplication of the long arm of chromosome 1, involving variable bands but consistently including 1q23. Among AIDS-related BL similar chromosome 1q abnormalities have also been found. We have now characterized in detail the chromosome 1q abnormalities of 4 AIDS-BL cell lines and compared them to other molecular features of the tumor clone, namely infection by Epstein Barr virus (EBV). Immunophenotypic characteristics were also assessed by conventional in situ immunocytochemical and flow cytometric procedures. The B-cell origin of all cell lines was demonstrated by the expression of B-cell-restricted markers (e.g., CD19). Analysis of Ig light chains confirmed their monoclonal nature. The t(8;14) was present in 3 of the 4 lines, whereas variant translocation t(8;22) was detected in the remaining cell line. Additional chromosomal changes were found in all cases, with chromosome 1 being involved in all. Structural changes encompassed in each case the 1q21-25 bands, in either duplication or partial trisomy. EBER ISH studies identified EBV association in 3 of the 4 AIDS-BL cell lines in contrast to previous studies of BL of immunocompetent individuals. Our findings of a high frequency of chromosome 1q abnormalities in EBV-infected AIDS-related BL cell lines demonstrate that such chromosomal abnormality and EBV positivity are not mutually exclusive and are possibly independent factors, whereas their close association in AIDS may be related to the immunodeficiency.

Burkitt Lymphoma↗