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M Boiocchi

Publications and source records attributed to M Boiocchi.

At least 109 records · Page 6Linked to original sources
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

Identification and characterization of an Epstein-Barr virus-specific T-cell response in the pathologic tissue of a patient with Hodgkin's disease.

Several lines of evidence indicate that an impairment of EBV-specific immune responses may contribute to the pathogenesis of Hodgkin's disease (HD). At present, however, it is not clear whether a defective immunity to EBV is a characteristic restricted to EBV-associated HD cases or a more generalized phenomenon, part of the inherent immune deficiency of HD patients. In this study, we have addressed this issue by analyzing EBV-specific responses in infiltrating T lymphocytes (TILs) from one HD biopsy, where the virus was confined to a small proportion of apparently normal lymphocytes. TIL cultures were established using low amounts of recombinant interleukin 2 and in the absence of specific stimulation, conditions that preferentially induce the proliferation of in vivo activated T cells. An EBV-specific cytotoxic component was revealed by the capacity of these TILs to lyse autologous EBV-positive lymphoblastoid cell lines (LCLs) obtained by spontaneous transformation from the lesion but not HLA-mismatched LCLs and autologous phytohemagglutinin blasts. This cytotoxic activity closely resembled that of EBV-specific memory T cells, which may be reactivated from the blood lymphocytes of healthy donors by in vitro stimulation with autologous LCLs. The use of a panel of appropriately HLA-matched B95.8-transformed LCLs as targets in standard 51Cr release assays revealed EBV-specific cytotoxic responses to be restricted mainly through the A11 and B44 HLA alleles with a minor HLA-A26-restricted component. Using autologous fibroblasts infected with recombinant vaccinia viruses expressing the EBV latent antigens, the TIL culture was shown to recognize latent membrane protein 2 and, to a lesser extent, EBV-encoded nuclear antigen 6. In addition, a strong proliferative response was induced by coculture of TILs with autologous but not with allogeneic LCLs or autologous phytohemagglutinin blasts. Six CD4-positive, EBV-specific T-cell clones were isolated by limiting dilution. The study of cytokine mRNA expression, carried out by reverse transcriptase-assisted PCR, revealed that three of these T-cell clones expressed a Th0 phenotype, whereas 1 had a Th2 phenotype. These findings are consistent with the presence in this HD lesion of an ongoing immune response against EBV-carrying cells and suggest that the complex immune deficiency that characterizes HD patients probably does not include a generalized, constitutional defect of EBV-specific T-cell responses.

Adult↗
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

Analysis of the p53 gene in relation to tobacco and alcohol in cancers of the upper aero-digestive tract.

To elucidate the relationship, if any, of p53 gene expression according to smoking and drinking habits, 135 subjects with cancer of the upper aero-digestive tract were sampled from a case-control investigation conducted in Pordenone province, Northeast Italy, between 1986 and 1991. Adequate pathological material for immunohistochemical analysis was available for 83 subjects. Level of p53 expression was classified according to intensity on immunoreaction and percentage of p53-positive cells. Mutations were analyzed by means of single-strand conformation polymorphism and sequencing in 8 p53-positive life-long non-smokers exposed to various levels of alcohol intake. The association between p53 expression and smoking status and alcohol intake was evaluated by means of odds ratios, and 95% confidence intervals. Significantly, more men (39/65) than women (6/18) had elevated p53 expression. No significant trend of increasing percentage of p53-positive cancers with increasing smoking and drinking level was detected, especially after allowance for gender. With respect to specific mutation pattern, in 8 life-long non smokers who drank alcohol, 6 mutations involved G:C base pairs. G-to-A transitions were identified in 4 cases. The present study does not support an association between elevated p53 expression and tobacco smoking or alcohol intake. It provides an example of a molecular biology study in the framework of a large epidemiological investigation.

Aged↗
PubMed1995

Head and neck lymphomas associated with human immunodeficiency virus infection.

OBJECTIVE: To focus on clinicopathologic data of non-Hodgkin's lymphomas (NHLs) of the head and neck area (with lymph nodal or extranodal localization) arising in patients with immunodeficiency virus (HIV) infection. PATIENTS: Among 73 evaluable patients for presenting symptoms, of a total of 82 with HIV-related NHLs whose conditions were diagnosed at the Centro di Riferimento Oncologico, Aviano (Italy), between September 1984 and May 1992, 15 (21%) had primary, solitary head and neck (P-HN) lymphoma and 13 (18%) had systemic head and neck (S-HN) lymphoma arising from this region. RESULTS: Ten (67%) of 15 patients with P-HN NHL had stages I and II, whereas all patients with S-HN NHL had stages III and IV. Twenty-seven of 28 patients had extranodal disease at presentation, the principal sites being Waldeyer's ring and soft tissues. There were only high-grade (14 cases) or intermediate-grade (three cases) NHLs, the most frequent histotypes being small noncleaved cell, Burkitt's type, and large-cell immunoblastic. Seven of 11 cases in the miscellaneous group of the working formulation were classified as Ki-1+ anaplastic large-cell lymphoma. By immunophenotypic and genotypic characterization, a B-cell derivation was suggested for 21 of 28 NHLs. After combination chemotherapy with or without radiotherapy, a complete remission was observed in seven (58%) of 12 patients with P-HN lymphoma and in only two patients with S-HN lymphoma. Median survival was 9.8 months for the patients with P-HN lymphoma and 8.3 months for the other patients. Thirteen patients died, the most common causes of death being opportunistic infections (five cases) and progression of lymphoma (four cases). CONCLUSIONS: Most HIV-infected patients with head and neck NHL had severe immunodeficiency, extranodal disease, aggressive histologic findings, and a poor treatment response.

Adult↗
PubMed1995

Genotypic and immunohistological demonstration of the progression of an unusual reactive-like B-cell lymphoproliferative disorder to a high grade diffuse lymphoma.

In the present study the clinical and pathological evolution of a reactive-like B-cell lymphoproliferative disorder with an unusually high content of T cells is described. Immunogenotypic analysis showed that the same phenotypically atypical B-cell clone, characterized by the unusual presence of an immunoglobulin (Ig)K gene rearrangement, with the heavy chain (IgH) gene in germline configuration, was invariantly present in all phases of the disease. The disorder showed an indolent course for a long period of time during which the clonal B-cell population coexisted with an abundant, reactive T-cell component in different locations of the disease. These findings, together with the observation of spontaneous progression and regression phases of the disorder and its responsiveness to corticosteroids, suggest that functional interactions between the B-cell clone and the polyclonal infiltrating T cells probably were involved in the pathogenesis of the disease. After the administration of the antiblastic treatment, a progressive reduction of the reactive T-cell component was observed with the concomitant evolution to a diffuse large cell (immunoblastic) B-cell lymphoma and the appearance of an IgH gene rearrangement. The biological characteristics and the clinical evolution of the case described here are similar to those reported for the so-called "T-cell-rich B-cell lymphomas" (TCRBCLs). These findings suggest that the T-cell-rich pattern may identify a group of B-cell lymphoproliferations with common pathogenetic mechanisms and clinical behavior.

Adult↗
PubMed1995

Pharmacokinetics of doxorubicin co-administered with high-dose verapamil.

The potential for the modification of the pharmacokinetics of doxorubicin (DOX) concurrently administered with high-dose verapamil (VER) has been investigated in 17 patients with advanced neoplasms refractory to drugs belonging to the multidrug resistance spectrum. Steady-state concentration of DOX, systemic clearance and urinary excretion were analysed. No significant difference was found between the kinetic parameters estimated for DOX at different levels of VER and those reported for doxorubicin as single agent. It can be concluded that VER does not appear to modify DOX kinetics.

Adult↗
PubMed1995

Recurrences and second primary tumours in the head and neck region: differentiation by p53 mutation analysis.

BACKGROUND: Patients with head and neck cancer are at high risk of developing additional primary tumours in the aerodigestive tract as a result of field cancerization phenomena. In this context, the appearance of a new neoplasm often poses a problem of differential diagnosis between recurrence and new primary tumour. The differentiation between the two entities in essentially clinical and conventionally based on the histological and spatio-temporal relations between the two lesions; however, the validity of these criteria has still to be assessed. DESIGN: To evaluate whether field cancerization phenomena may affect the clinical diagnosis of relapse/metastasis in the head and neck region, p53 mutation pattern was analysed in a series of primary tumours and corresponding recurrences/metastases. The rationale was that, since p53 mutations are a very early and polymorphic phenomenon, a recurrence/metastasis must retain the same mutation as the the primary tumour, whereas independent tumours are likely to display a different p53 gene status. RESULTS: Molecular analysis provided conclusive results in 9 of 12 cases analysed. The clinical diagnosis of recurrence was confirmed by molecular analysis in 4 of these cases. In contrast, a differential p53 mutation pattern supported an independent origin for 3 presumed local recurrences and 2 lung lesions. CONCLUSIONS: The use of p53 mutation analysis as a clonality marker allowed us to ascertain the inadequacy of the current diagnostic criteria for the differentiation between a new independent tumour and recurrence/metastasis. These findings substantiate the relevance of field cancerization phenomena in the head and neck region and prompt the use of p53 mutation analysis as a fundamental tool to improve the diagnosis and management of head and neck cancers.

Adult↗
PubMed1995

Effect of cyclosporine on teniposide pharmacokinetics and pharmacodynamics in patients with renal cell cancer.

Five patients with metastatic renal cell cancer (RCC) entered this study. The patients received two courses of teniposide (VM26) (200 mg/m2/24 h i.v.) after which no objective response was observed: three patients had stable disease (SD) and two had progressive disease. Cyclosporine (CsA) (5 mg/kg/2 h followed by 30 mg/kg/48 h i.v.) was then added (VM26/CsA) and at least another two courses were administered. Pharmacokinetic and pharmacodynamic parameters were analyzed. CsA increased the area under curve (AUC) of VM26 in four out of five patients; on average, the variation in the paired AUC of VM26 was 41%. Nadir granulocyte count was lower (average 650/mm3, ranging from < 100 to 1800/mm3) after VM26/CsA than after VM26 (average 1260/mm3, ranging from 200 to 2100/mm3) (p < 0.01). Bilirubin concentration in the serum was increased after VM26/CsA compared with VM26 (p < 0.05). Finally, after two courses of VM26/CsA, four patients had stable disease and one patient had a minor response. In conclusion, the ongoing pilot study indicates that CsA affects both the pharmacokinetics and the pharmacodynamics of VM26.

Aged↗
PubMed1995

DNA flow cytometric evaluation of cell cycle distribution in ulcerative colitis: a proposed method for assessing severity of disease.

The assessment of disease severity in ulcerative colitis depends mainly on subjective variables, and an objective method of assessing mucosal inflammation is needed. Determination of the synthetic phase of the cell cycle is an accurate expression of inflammatory activity in the colonic mucosa. The aim of the study was to find out if the proliferative index or the synthetic phase (S phase) of the colonic mucosa of patients with ulcerative colitis, as evaluated by DNA flow cytometry, is a reliable and reproducible marker of disease activity. Sixty consecutive patients with ulcerative colitis of different degrees of activity were entered into the study and submitted to colonoscopy plus multiple rectal biopsies. Disease severity was defined for each patient by means of a clinical, endoscopic, and histological score. Flow cytometry was used to calculate the proliferative index and the S phase of the cell cycle. A statistically significant correlation (p < 0.001) was found between all indices of severity. It is suggested that flow cytometric evaluation of the cell cycle in the rectal mucosa may be an efficient method of assessing severity of disease and efficacy of medical treatment in ulcerative colitis.

Adult↗
PubMed1995

Hodgkin's disease and human immunodeficiency virus infection: clinicopathologic and virologic features of 114 patients from the Italian Cooperative Group on AIDS and Tumors.

PURPOSE: To describe virologic, clinicopathologic, and therapeutic features of a large series of Italian patients with Hodgkin's disease (HD) and human immunodeficiency virus (HIV) infection. PATIENTS AND METHODS: From November 1986 to March 1994, 114 cases were observed. The relationship between Epstein-Barr virus (EBV) and HD was determined by an in situ hybridization technique, immunostaining for EBV-encoded latent membrane protein-1 (LMP-1) expression, and Southern blotting. Twenty-six patients were included in a prospective study evaluating the combination of chemotherapy (CT) with zidovudine. RESULTS: Combined approach on EBV study revealed that 14 (78%) of 18 patients were EBV-associated. An almost equivalent distribution of EBV subtypes was observed in EBV-carrying cases, indicating that in the HIV setting, type 2 EBV also may be pathogenetically involved in HD development. In comparing these 114 patients with our single-institutional series of 104 HIV-negative patients with HD, we observed at presentation a younger median age (29 v 38 years); a prevalence of males (90% v 56%); and a higher percentage of stage IV disease (52% v 15%), presence of B symptoms (77% v 35%), and extranodal disease (63% v 29%). The complete remission (CR) rate (58%) and median survival (13 months) of patients treated prospectively were similar to that of patients treated with standard CT regimens. The statistically significant favorable prognostic factors for survival being the following: achievement of CR, CD4+ count greater than 250/microL, and no prior diagnosis of AIDS at onset of HD. CONCLUSION: Our virologic findings indicate that HIV-related HD is more closely associated with EBV than HD in the general population. The peculiar clinicopathologic findings, the role of some prognostic factors, and the possibility of cure of HIV-related HD have been demonstrated.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Brief report: prognostic importance of cellular DNA content in T1-2 N0 laryngeal squamous cell carcinomas treated with radiotherapy.

One hundred fifty-two unselected, consecutive patients with T1-2N0 laryngeal squamous cell carcinoma received radical radiation therapy at the Division of Radiotherapy, Centro di Riferimento Oncologico, Aviano, Italy. Thirty-one (20.4%) of the patients showed disease recurrence or persistence (R/P) after radiotherapy. Flow-cytometric DNA ploidy measurements were performed in 72 cases; 20 had tumor R/P and 52 did not. Tumor R/P occurred more frequently (in 17 [85%] of 20 cases) in patients with diploid tumors. The hazard ratio of recurrence in diploid tumors as compared with aneuploid tumors, after inclusion of all the other significant prognostic factors in a Cox proportional hazards model, was 8.9 (P < .01). Therefore DNA ploidy seems to be an important marker of tumor R/P in patients with T1-2N0 laryngeal carcinoma after radiotherapy.

Carcinoma, Squamous Cell↗