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Biomedical subjects

A Carbone

Publications and source records attributed to A Carbone.

At least 73 records · Page 4Linked to original sources
PubMed2001

Differential expression of transforming growth factors-beta1, -beta2 and -beta3 in human colon carcinoma.

Transforming growth factor (TGF)-beta is a protein family which affects multiple cellular functions including survival, proliferation, differentiation and adhesion. Among the three known isoforms, TGF-beta1 is commonly overexpressed in solid malignancies. Recent studies in knock-out mice demonstrated non-redundant roles of different TGF-beta isoforms in development. The present study was performed to assess tumour-associated expression of the three TGF-beta isoforms in colon carcinoma. We report that colon carcinoma progression is associated with gradual and significant increases in expression of TGF-beta1 and TGF-beta2 mRNA and proteins. By contrast, TGF-beta3 expression was detected in normal colonic mucosa and, at slightly higher levels, in tumour tissues. In addition, plasma levels of both TGF-beta1 and TGF-beta2 were significantly higher in cancer patients when compared with unaffected individuals. Taken together, our results indicate distinct expression patterns of the three TGF-beta isoforms in colon carcinoma cells and possible systemic effects of TGF-beta1 and TGF-beta2 in tumour patients.

Adult↗
PubMed2001

Acquired immunodeficiency syndrome-related cancer. A study model for the mechanisms contributing to the genesis of cancer.

The study of AIDS and cancer has resulted in an important convergence of clinical-epidemiological investigations, molecular research and virological studies. This shared effort has led to significant discoveries in the field of human carcinogenesis. In a relatively short time, several topics have been clarified, namely: (1) the spectrum of AIDS-related tumours has been identified; (2) the role of HIV in lymphomagenesis and in the development of Kaposi's sarcoma (KS) has been defined; (3) AIDS-related cancers have allowed the discovery and extensive biological characterisation of the novel virus human herpes virus 8 (HHV8), also called KS-associated herpesvirus; and (4) genetic, molecular, and phenotypic studies of AIDS-related lymphomas have contributed to the formulation of a pathogenetic and histogenetic model of B-cell non-Hodgkin's lymphomas (NHL).

Acquired Immunodeficiency Syndrome↗
PubMed2001

Pathogenetic and histogenetic features of HIV-associated Hodgkin's disease.

Compared with the cases in the general population, Hodgkin's disease (HD) arising in the HIV setting shows distinctive features in terms of epidemiology, aetiopathogenesis, histopathology and clinical behaviour. Although HD does not represent an AIDS-defining condition, recent evidence consistently indicates that HIV-infected individuals have a significantly increased risk of developing HD. HIV-related HD is characterised by the preponderance of aggressive histological subtypes, advanced stage at presentation, and highly malignant clinical course. Moreover, unlike HD in the general population, the large majority of HIV-related HD cases are pathogenetically linked to Epstein-Barr virus (EBV), with rates of EBV positivity ranging from 80 to 100%. Hodgkin and Reed-Sternberg cells of these cases invariably show a strong expression of the EBV-encoded latent membrane protein-1 (LMP-1), which functions as a constitutively activated tumour necrosis factor (TNF) receptor-like molecule. Usurpation of physiologically relevant pathways by LMP-1 may lead to the simultaneous or sequential activation of signalling pathways involved in the promotion of cell activation, growth, and survival, contributing thus to most of the features of HIV-related HD.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Genetic pathways and histogenetic models of AIDS-related lymphomas.

Acquired immunodeficiency syndrome (AIDS)-related lymphomas consistently display a B-cell phenotype and are histogenetically related to germinal centre or post-germinal centre B cells in the overwhelming majority of cases. The pathogenesis of AIDS-related lymphoma is a multistep process involving factors provided by the host as well as alterations intrinsic to the tumour clone. The molecular pathways of viral infection and lesions of cancer-related genes associated with AIDS-related lymphomas vary substantially in different clinicopathological categories of the disease and highlight the marked degree of biological heterogeneity of these lymphomas.

Burkitt Lymphoma↗
PubMed2001

A 20-year experience on malignant lymphomas in patients aged 70 and older at a single institute.

We have evaluated the clinico-pathological and therepeutical outcome of patients aged 70 and older with malignant lymphomas treated at a single institute over a 20-year period of time. Among the several studies evaluated, the most important is a prospective randomized study comparing a new regimen, VMP (VP 16, Mitoxantrone and Prednimustine) vs the goal standard CHOP in unfavorable non-Hodgkin's lymphoma (NHL), showing that CHOP is significantly better than VMP in terms of objective response rate, progression free and overall survival. Therefore CHOP remains the standard regimen also for patients of over 70 years of age and stage II--IV intermediate and high grade NHL.

Aged↗
PubMed2001

Management of hematologic malignancies in the elderly: 15-year experience at the Aviano Cancer Center, Italy.

The optimal management of hemopoietic malignancies in the elderly requires specific strategies targeted at the peculiar clinico-biologic features of such patients. In the time frame spanning from 1983 to 1998, several clinical trials have been performed at the Aviano Cancer Center, Italy, aimed at extending the knowledge of natural history of hemopoietic malignancies in the elderly and evaluating the efficacy and toxicity of different chemotherapy programs specifically devised for older subjects affected by acute myeloid leukemia, myelodysplasia, non-Hodgkin's lymphomas, or multiple myeloma. Here the most relevant results are summarized and information stemmed from such studies. The present report rather than provide a comprehensive review on hematologic neoplasms in the elderly, mainly reflects the 'philosophy' deriving from 15 years of studies of the group in the field of geriatric oncology/hematology. Elaboration of a 'consensus' view will represent the challenge for all the investigators involved in such an important field of research.

Aged↗
PubMed2001

Bladder filling inhibits somatic spinal motoneurones.

OBJECTIVES: Despite evidence that the activation of visceral afferents modulates spinal motoneurone activity in humans the responsible circuits remain unclear. We investigated changes in spinal motoneurone excitability during bladder filling in 8 healthy subjects and in 8 patients with spinal cord lesions and 5 patients with multi-infarct encephalopathy. METHODS: Spinal motoneurone excitability was studied by analysing changes in H-reflex, F-wave and motor-evoked potential (MEP) size recorded from the calf muscles under different bladder filling conditions. RESULT: In normal subjects, maximal bladder filling significantly suppressed the H-reflex, F-wave and MEPs; after bladder voiding these responses returned to normal. In patients with encephalopathy maximal bladder filling strongly reduced H-reflex size; similarly to normal subjects H-reflex returned to control value after bladder voiding. In patients with spinal cord lesions, activation of bladder afferents left the H-reflex unchanged. CONCLUSIONS: These findings indicate that bladder distension induces post-synaptic inhibition of spinal motoneurones through a suprasegmental pathway, which is interrupted by rostral spinal cord lesions. This vesical-induced inhibition is probably mediated by the propriospinal system rather than by the diffuse noxious inhibitory control circuit.

Adult↗
PubMed2001

Among diffuse large B-cell lymphomas, T-cell-rich/histiocyte-rich BCL and CD30+ anaplastic B-cell subtypes exhibit distinct clinical features.

BACKGROUND: The EORTC clinical trial 20901, activated in 1990, was designed to treat non-Hodgkin's lymphomas (NHL) of intermediate/high-grade malignancy according to the Working Formulation. Established in 1994, the R.E.A.L. Classification on NHL has now replaced all former classifications. PATIENTS AND METHODS: We reanalysed all cases (n = 273) documented by material available for review according to the R.E.A.L. Classification. In addition, we subdivided cases recognised as diffuse large B-cell lymphoma (DLBCL) into three morphologically distinct categories, namely, large cleaved DLBCL (LC-DLBCL), T-cell-rich/histiocyte-rich B-cell lymphoma (T-cell-rich/histiocyte-rich BCL) and CD30+ DLBCL with anaplastic cell features (CD30+ DLBCL). Finally, T/NULL anaplastic large-cell lymphoma (ALCL) cases were subdivided into ALK+ and ALK- lymphomas. Review was performed independently by two pathologists from two different centres. RESULTS: DLBCL (61%), T/NULL ALCL (15%) and mantle-cell lymphoma (MCL, 50%) were the main NHL categories represented in the study. Fifty-seven of one hundred sixty DLBCL cases were further subclassified as LC-DLBCL (33 cases), T-cell-rich/histiocyte-rich BCL (13 cases) or CD30+ DLBCL (11 cases). The remaining cases were indicated as unspecified DLBCL. A clinico-pathological correlation confirmed the findings of previous studies suggesting that MCL, DLBCL and ALCL represent distinct entities with MCL being characterised by a short survival, in contrast with the longer survival and less frequent progression typical of ALK+ compared to ALK- ALCL. Within DLBCL, T-cell-rich/histiocyte-rich BCL showed distinctive features at presentation whereas CD30+ DLBCL showed a trend towards a more favourable prognosis, that might be comparable to that of ALK+ ALCL. CONCLUSIONS: Our data further support the usefulness of the R.E.A.L. Classification and illustrate the feasibility of DLBCL subtyping. Moreover, our results demonstrate the distinct clinical characteristics of T-cell-rich/histiocyte-rich BCL and CD30+ DLBCL with anaplastic cell features suggesting that they may represent clinico-pathologic entities.

Adolescent↗
PubMed2000

Sequence analysis of the immunoglobulin antigen receptor of hepatitis C virus-associated non-Hodgkin lymphomas suggests that the malignant cells are derived from the rheumatoid factor-producing cells that occur mainly in type II cryoglobulinemia.

Analysis of the immunoglobulin receptor (IGR) variable heavy- and light-chain sequences on 17 hepatitis C virus (HCV)-associated non-Hodgkin lymphomas (NHLs) (9 patients also had type II mixed cryoglobulinemia [MC] syndrome and 8 had NHL unrelated to MC) and analysis of intraclonal diversity on 8 of them suggest that such malignant lymphoproliferations derive from an antigen-driven pathologic process, with a selective pressure for the maintenance of a functional IgR and a negative pressure for additional amino acid mutations in the framework regions (FRs). For almost all NHLs, both heavy- and light-chain complementarity-determining regions (CDR3) showed the highest similarity to antibodies with rheumatoid factor (RF) activity that have been found in the MC syndrome, thus suggesting that a common antigenic stimulus is involved in MC syndrome and in HCV-associated lymphomagenesis. Moreover, because HCV is the recognized pathologic agent of MC and the CDR3 amino acid sequences of some HCV-associated NHLs also present a high homology for antibody specific for the E2 protein of HCV, it may be reasonable to speculate that HCV E2 protein is one of the chronic antigenic stimuli involved in the lymphomagenetic process. Finally, the use of specific segments, in particular the D segment, in assembling the IgH chain of IgR seems to confer B-cell disorders with the property to produce antibody with RF activity, which may contribute to the manifestation of an overt MC syndrome.

Aged↗
PubMed2000

Pre-malignant and malignant lymphoproliferations in an HCV-infected type II mixed cryoglobulinemic patient are sequential phases of an antigen-driven pathological process.

Type II mixed cryoglobulinemia (MC) is a systemic vasculitis characterized by the presence in the serum of a monoclonal cryoprecipitable IgM with rheumatoid factor (RF) activity. Hepatitis C virus (HCV) has been recognized as its major etiologic factor. Because MC frequently evolves into overt B-cell non-Hodgkin's lymphoma (NHL), chronic HCV infection is hypothesized to lead to both benign and malignant lymphoproliferative disease. In this study, we investigated mutations in the V(H) and V(K) genes of the B-cell clone originating the overt B-cell lymphoma in a subject with MC. Mutational patterns were analyzed longitudinally in two bone marrow biopsies obtained at the stage of MC, as well as in multiple involved tissues (bone marrow, liver, and peripheral blood cells) at the stage of overt NHL. Hybridization of variable-diversity-joining (VDJ) PCR products with a probe specific for the neoplastic clone indicated that the lymphoma originated from one of the clones over-stimulated during MC. This clone producing an IgM highly homologous to a protein with RF specificity may explain the MC syndrome in the patient. Moreover, the presence of an IgH ongoing mutation process and the expression of an Ig antigen receptor significantly homologous to an anti-HCV protein support the hypothesis that the MC syndrome and the subsequent evolution to NHL are antigen-driven lymphoproliferative processes possibly sustained by HCV. Furthermore, the marked reduction in intra-clonal diversity in the last bone marrow biopsy obtained at the stage of overt NHL points out a minor dependence of the cells on the antigen-driven mechanism, although an intrinsic propensity of the neoplastic cell to undergo replacement mutations cannot be excluded.

Amino Acid Sequence↗
PubMed2000

Primary cytoreductive surgery with rectosigmoid colon resection for patients with advanced epithelial ovarian carcinoma.

BACKGROUND: The impact of radical bowel resection with multiple organ resection on the survival if patients with advanced ovarian carcinoma has not been well defined. The authors investigated whether primary cytoreductive surgery including rectosigmoid colon resection would affect the recurrence free interval and survival of these patients. METHODS: Between April 1990 and April 1997, 66 previously untreated Stage IIIC-IV ovarian carcinoma patients with macroscopic involvement of the rectosigmoid colon were enrolled. All patients underwent cytoreductive surgery with rectosigmoid colon resection to remove residual tumor less than 2 cm in greatest dimension and received 6 cycles of cisplatin-based postoperative chemotherapy. RESULTS: The median follow-up was 26 months (range, 7-104 months). In multivariate analysis, residual disease and depth of tumor infiltration of the bowel wall were independently associated with overall survival and recurrence free interval. Disease stage was independently associated only with overall survival. Residual tumor was the most strongly predictive factor for recurrence or death. The 2-year estimated survival rates according to the amount of residual tumor were 100% for 24 patients with no macroscopic residual disease and 77.3% for 28 patients with residual disease less than 1 cm. None of the 14 patients with residual disease larger than 1 cm were alive 2-years after operation. Overall, 48 patients (72.7%) developed disease recurrence: 43 (65.1%) in the abdomen, 19 (29.8%) in the liver, and 3 (4.5%) in the pelvis. CONCLUSIONS: The current findings suggest that cytoreductive surgery with rectosigmoid colon resection should be considered for ovarian carcinoma patients with bulky pelvic disease to help ensure that they are left with no residual disease after debulking surgery.

Adult↗
PubMed2000

Distribution and pattern of BCL-6 mutations throughout the spectrum of B-cell neoplasia.

BCL-6 mutations are accumulated during B-cell transit through the germinal center (GC) and provide a histogenetic marker for B-cell tumors. On the basis of a comprehensive analysis of 308 B-cell neoplasms, we (1) expand the spectrum of tumors associated with BCL-6 mutations; (2) corroborate the notion that mutations cluster with GC and post-GC B-cell neoplasms; and (3) identify heterogeneous mutation frequency among B-lineage diffuse large cell lymphoma (B-DLCL) subsets. Mutations are virtually absent in acute lymphoblastic leukemia (P <.001) and mantle cell lymphoma (P <.05), whereas they occur frequently in GC or post-GC neoplasms, including lymphoplasmacytoid lymphoma, follicular lymphoma, MALT lymphomas, B-DLCL and Burkitt lymphoma. Among B-DLCL, mutations occur frequently in systemic nodal B-DLCL, primary extranodal B-DLCL, CD5(+) B-DLCL, CD30(+) B-DLCL, and primary splenic B-DLCL, suggesting a similar histogenesis of these B-DLCL subsets. Conversely, mutations are rare in primary mediastinal B-DLCL with sclerosis (10.0%; P <.01), supporting a distinct histogenesis for this lymphoma. Longitudinal follow-up of B-DLCL transformed from follicular lymphoma shows that they BCL-6 mutations may accumulate during histologic progression. Mutations also occur in some B-cell chronic lymphocytic leukemias, small lymphocytic lymphomas, and hairy cell leukemias, consistent with the hypothesis that a fraction of these lymphoproliferations are related to GC-like cells. Finally, the molecular pattern of 193 mutational events reinforces the hypothesis that mutations of BCL-6 and immunoglobulin genes are caused by similar mechanisms. (Blood. 2000;95:651-659)

Base Sequence↗