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M Boiocchi

Publications and source records attributed to M Boiocchi.

At least 145 records · Page 8Linked to original sources
PubMed1993

High-mobility-group (HMG) proteins and histone H1 subtypes expression in normal and tumor tissues of mouse.

Exhaustive extraction of mouse tissues with perchloric acid has been used together with reverse-phase HPLC and electrophoresis to quantify the amounts of chromosomal proteins HMG17, HMG14 and HMGI, relative to histone H1. Normal lung and thymus contain approximately 3% HMG17/HMG14 but only approximately 2% HMGI. In tumor tissues (Lewis lung carcinoma and lymphoma NQ35), the amount of HMG17/HMG14 is not greatly altered but HMGI levels rise considerably, reaching 10% in Lewis lung carcinoma. HMGI synthesis does not replace HMG17/HMG14 proteins, suggesting that HMGI proteins contribute to the structure of chromatin regions in a manner distinct from those of HMG17/HMG14. Ion-spray mass spectrometry has been used to determine the molecular masses of H1 subtypes from the same four mouse tissues. In addition to the six known species H1 zero, H1a, H1b, H1c, H1d and H1e, a newly defined subtype of mass 21,756 Da from Lewis lung carcinoma, named H1L was identified. Several phosphorylated H1 subtypes have also been defined by mass spectrometry. The combined use of reverse-phase HPLC and electrophoresis permitted quantification of these seven histone H1 subtypes in the four mouse tissues. Increased phosphorylation of H1 subtypes in tumors parallels the phosphorylation of HMGI proteins which are present in great amounts, showing that both are involved as post-translational-modified forms in the structure of the chromatin of neoplastic systems.

Animals↗
PubMed1993

Increased chemosensitivity to doxorubicin of intrinsically multidrug-resistant human colon carcinoma cells by prolonged exposure to verapamil.

Resistance modifying agents (RMA) such as verapamil (VER) have proved effective in reversing multidrug resistance (MDR) in many in vitro experimental models, but clinical results with RMA have been disappointing. To clarify this apparent discrepancy we have evaluated the cytotoxic effects of doxorubicin (DOX) plus VER in four human colon carcinoma (HCOC) cell lines (LoVo, DLD-1, SW948, SW1116). These lines were selected on the basis of their levels of mdr1 mRNA being similar to those expressed by HCC obtained from non-drug-treated patients. In all cell lines the sensitising effect of VER on DOX cytotoxicity was schedule-dependent and maximal potentiation of DOX cytotoxicity was obtained by exposure to VER for a time > or = the cells' population doubling time.

Cell Survival↗
PubMed1993

Type 2 Epstein-Barr virus genome and latent membrane protein-1 expression in a T-cell-rich lymphoma of probable B-cell lineage.

In a 79-year-old white woman, a lymphoproliferative disorder that was associated with type 2 Epstein-Barr virus (EBV) infection or reactivation, documented by three subsequent lymph node biopsies, was studied. After an initial phase with features of reactive lymphadenopathy with exhaustion of the follicular germinal centers and depletion of the B-cell lymphoid population, the disease evolved to a T-cell-rich lymphoma in which a clonal cell population of probable B-cell origin was identified. Such clonal cell population harbored the viral genome and expressed EBV latent membrane protein-1 but not EBV nuclear antigen-2. The implications of immunologic interactions between the clonal EBV-infected cells and the reactive T-cell component in the pathogenetic process are discussed.

Aged↗
PubMed1993

Human immunodeficiency virus-associated systemic lymphomas may be subdivided into two main groups according to Epstein-Barr viral latent gene expression.

PURPOSE: We report a pathologic characterization of human immunodeficiency virus (HIV)-associated systemic lymphomas, including the association of Epstein-Barr virus (EBV) in different categories. PATIENTS AND METHODS: Eighty-seven HIV-associated non-Hodgkin's lymphoma (NHL) were classified according to classic NHL classification and a recent description of morphologic variants of high-grade B-cell NHL. Seventy-one cases were immunophenotypically-genotypically characterized, whereas, in 49 representative cases, the association of EBV was assessed by nonisotopic in situ hybridization (ISH) and the immunohistochemical demonstration of latent membrane protein-1 (LMP-1). In addition, 14 Hodgkin's disease (HD) cases, occurring in patients with HIV infection, were investigated for the frequency of LMP-1 expression. RESULTS: Most lymphomas were of B-cell derivation and showed a blastic cell morphology, with (1) small noncleaved cells (SNCCs; 36 cases), (2) large noncleaved cells (10 cases), and (3) immunoblasts, usually polymorphic (12 cases). Moreover, 12 cases were classified as anaplastic large-cell (ALC) Ki-1-positive (Ki-1+) lymphoma. Combined ISH studies (for viral DNA and EBV RNA [EBER]) and immunohistologic demonstration of LMP-1 suggested that there were differences in viral latent gene expression between ALC Ki-1+ or immunoblastic lymphomas (usually EBV+, LMP-1+), and EBV-infected cells of SNCC lymphomas, which did not show LMP-1 expression. A high proportion (10 of 14) of LMP-1+ HD cases was found. CONCLUSION: Differences in EBV association and LMP-1 expression were found between a major group of HIV-associated systemic NHL with blastic cell morphology, including SNCC lymphoma and its variants, and anaplastic cell lymphomas. A proportion of immunoblastic (polymorphic) lymphomas was different in viral latent gene expression from other blastic cell systemic lymphomas. It is concluded that only a group of these lymphomas (most ALC Ki-1+ and HD cases, along with a nonnegligible fraction of immunoblastic lymphomas) seems to be linked etiopathologically to EBV.

Gene Expression Regulation, Viral↗
PubMed1993

Demonstration of a unique Epstein-Barr virus-positive cellular clone in metachronous multiple localizations of Hodgkin's disease.

The recent detection of clonal episomes of Epstein-Barr virus (EBV) in a significant proportion of Hodgkin's disease (HD) cases has suggested a re-evaluation of the possible pathogenetic role of EBV in the development of the disease. Here we report that in two EBV-positive HD, arisen in human immunodeficiency virus-1-infected drug users, a unique episomal EBV genome was detected in multiple metachronous HD lesions of each patient. These findings demonstrated that the same EBV-positive cellular clone was present in multiple localizations of HD as well as in specimens taken at different times. Combined in situ hybridization and immunohistological analyses evidenced EBV genome and EBV-encoded latent membrane protein-1 on Reed-Sternberg cells. Therefore, the data strongly support the possibility of a causal role for EBV in the pathogenesis of HD.

Adult↗
PubMed1993

Doxorubicin, vincristine, and actinomycin-D, but not teniposide, require long-lasting uninterrupted verapamil pressure to overcome drug resistance in multidrug-resistant cells.

The cytotoxic efficacy of doxorubicin (DOX), vincristine (VCR), actinomycin-D (ACT-D), and teniposide (VM-26) toward the LoVo and SW948 multidrug-resistant (MDR) cell sublines was significantly enhanced by the concomitant presence of verapamil (VER) during pharmacological treatment (1-h exposure) without, however, achieving a complete reversion of the MDR phenotype. Long-lasting VER in the culture medium, at the end of the combined drug+VER treatment, conferred to DOX, VCR, and ACT-D cytotoxic efficacy roughly similar to that exerted on the drug-sensitive parent cell lines. On the contrary, no enhancement of VM-26 cytotoxic efficacy was derived from continuous VER treatment. Enhancement of DOX, VCR, and ACT-D cytotoxic efficacy requires that VER be present in an uninterrupted manner in the culture medium since brief interruptions (15 to 60 min) in the VER pressure completely counteract any effect. These findings offer new insight into the modalities of pharmacological treatment that MDR cells require to obtain a complete reversion of cellular resistance to the various drug families included in the MDR spectrum.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

p53 over-expression is an early event in the development of human squamous-cell carcinoma of the larynx: genetic and prognostic implications.

The tumor-suppressor protein p53 is over-expressed in a large fraction of squamous-cell carcinomas of the larynx (LSCCs). p53 overexpression is dependent upon the synthesis of mutated versions of the protein and has been associated with the malignant progression of certain tumor types. In order to examine the prognostic value of p53 immunodetection in LSCCs, we performed a retrospective analysis on a selected series of tumors, using the PAb 1801 and CM1 antibodies. No significant difference in the frequency of p53 over-expression was observed between tumors from patients with early relapse (67%) and those who had been disease-free for more than 5 years (84%). The lack of correlation of p53 immunoreactivity with clinical stage and differentiation grade of LSCCs, together with the coordinated expression of p53 in primary tumors and the corresponding lymph-node metastases, indicate that p53 over-expression is probably unrelated to the biological aggressiveness of these tumors. In addition, the detection of p53 immunostaining in pre-invasive areas as well as in preneoplastic lesions suggests that p53 abnormalities probably constitute a very early event in LSCC development.

Carcinoma in Situ↗
PubMed1992

Pathogenesis of human reactive-appearing "non-monomorphous" malignant lymphoproliferative disorders: a hypothesis.

Human reactive-appearing "non-monomorphous" malignant disorders, such as Hodgkin's disease, T-cell-rich B-cell lymphomas and angioimmunoblastic lymphadenopathy display a peculiar and unifying characteristic, which biologically differentiates them from "monomorphous" non-Hodgkin's lymphomas. It consists in the coexistence within the pathologic tissue of a polyclonal, normal-appearing, presumed reactive cellular component, mainly composed of T-lymphocytes together with a clonal cell component constituting a minority of the pathologic mass. To explain the long-lasting coexistence of such polymorphic cell populations in the pathologic tissue of synchronous and metachronous localizations of the disease, it is hypothesized that they are interconnected by "biological interactions" which determine and sustain the pathologic process. Based on the biological characteristics of an experimental model (the follicular center cell "lymphoma" of the SJL murine strain), it is suggested that these human "non-monomorphous" malignant diseases should be regarded as a continuous spectrum of lymphoproliferative disorders sustained by a biological loop which interconnects different cell populations able to stimulate each other for growth.

Animals↗
PubMed1992

P-glycoprotein but not topoisomerase II and glutathione-S-transferase-pi accounts for enhanced intracellular drug-resistance in LoVo MDR human cell lines.

The biochemical bases of the multidrug-resistant (MDR) phenotype were investigated in drug-resistant sublines derived from LoVo human colon carcinoma cell lines by doxorubicin (DOX) and teniposide (VM26) selection. In addition to P-glycoprotein-mediated drug extrusion through the plasma-membrane, LoVo MDR cells display a further drug-resistance mechanism. That is, to achieve equitoxic effects, LoVo MDR sublines require much higher intracellular drug concentrations than those required by LoVo drug-sensitive parent cell line. Involvement of mdr1, topoisomerase II and glutathione-S-transferase-pi (GST-pi) drug-resistance systems in intracellular drug resistance was investigated. Pharmacologic and biochemical data indicated that intracellular drug resistance in LoVo MDR sublines is uniquely consequent to the drug-transporting property of intracytoplasmic membrane-bound P-glycoprotein molecules which compartment drugs in vacuole-like structures.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Expression of the mdr1 gene in human colorectal carcinomas: relationship with multidrug resistance inferred from analysis of human colorectal carcinoma cell lines.

To investigate whether mdr1 gene products are involved in conferring the chemoresistant phenotype to human colorectal carcinomas (HCCs), we determined the mdr1 mRNA expression level (mdr1 EL) in surgical specimens from 29 pharmacologically untreated patients and analyzed the relationship between mdr1 EL and drug resistance in an in vitro experimental model. This consisted of 7 HCC cell lines chosen to cover the range of mdr1 ELs detected in the neoplastic specimens. No relationship was observed between the mdr1 EL of the HCC cell lines and the degree of chemosensitivity found for each drug tested, regardless of whether mdr1 gene products may [doxorubicin (DOX), vincristine (VCR), and actinomycin-D (ACT-D)] or may not affect [cis-diamminedichloroplatinum (CDDP)] drug-transmembrane equilibria. Conversely, a direct relationship was found between the mdr1 EL of HCC cell lines and the number of drug-resistant (DR) colonies arising from each parent cell line treated in continuous culture with high DOX concentrations. In addition, the chemoresistance index and mdr1 EL of the DR cell variants were roughly proportional to the mdr1 EL of the parent cell line. Our findings suggest that primary HCCs derive multidrug resistance from biochemical mechanism(s) other than mdr1 gene products. However, the mdr1 EL might be indicative of a predisposition to develop DR cell variants after chemotherapeutic treatment.

Antineoplastic Agents↗
PubMed1992

Mechanism of multidrug resistance in human tumour cell lines and complete reversion of cellular resistance.

The biochemical basis of the multidrug-resistant (MDR) phenotype has been investigated in drug-resistant sublines derived from LoVo and SW984 human colon carcinoma cell lines by doxorubicin selection. Besides drug extrusion through the plasma membrane, two further observations, both ascribable to the drug transport property of the gp170 glycoprotein, were made. First drug deposition into cytoplasmic membranous structures which allows cells to tolerate a high intracellular drug concentration since it prevents drugs from reaching their cellular target site(s). Secondly drug removal from the complexes formed by interaction of drug with target cellular macromolecules, a phenomenon which extends its an effect that continues after treatment and appears to be the most important resistance mechanism in MDR cells. Treatments based on the gp170 inhibitory property of verapamil were developed that allowed abrogation of resistance in MDR cell lines, a strategy that may be applicable to therapy treatments.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Expression of glutathione-S-transferase-pi in human tumours.

Expression of glutathione-S-transferase-pi (GST-pi) gene was quantitatively analysed on various human tumours (renal cell, colorectal, head and neck, ovarian carcinomas, soft tissue sarcomas; non-Hodgkin lymphomas) and on the corresponding normal tissues when available (kidney, colorectum and head and neck). GST-pi mRNA expression level was found to be significantly higher in tumours (P less than 0.01) than in the normal counterparts (mainly 7.3, 3.5- and 3.0-fold in colorectal, head and neck, and renal carcinomas, respectively). Most tumours displayed a significant relationship between higher GST-pi expression level and poor differentiation grade of tumour cells, thus suggesting a relationship between GST-pi activity, neoplastic transformation and cellular differentiation grade. The high requirement of GST-pi activity neoplastic cells displayed was not singularly related to cellular replication rate. Finally, GST-pi gene expression levels were not affected by chemotherapeutic treatments.

Adolescent↗
PubMed1992

Chromosomal localisation of two putative 11p oncosuppressor genes involved in human ovarian tumours.

In this study, 44 primary or metastatic human ovarian tumours were tested for allelic deletions on the short arm of chromosome 11. Analysis of 12 polymorphic loci by Southern blotting evidenced loss of heterozygosity (LOH) in at least one locus in 41% of cases. Moreover, two hot spots of deletions were tentatively mapped on 11p13 and 11p15.5. Our results demonstrated that LOH at 11p is a common event in ovarian carcinomas and were indicative of the possible existence in 11p of two oncosuppressor genes involved in ovarian carcinogenesis. The similarity observed with 11p allelic losses in Wilms tumours, clustered in 11p13 and 11p15.5 too, suggests that deletion and possibly inactivation of the same growth regulatory genes (WT genes) could also contribute to development of the malignant phenotype in ovarian carcinomas. Finally, a statistically significant association (P = 0.005) between 11p deletions and hepatic involvement was suggested by the analysis of distribution of 11p LOH relative to different clinical and pathological parameters of the tumour patients.

Adult↗
PubMed1992

Expression of MDR1 and GST-pi in human soft tissue sarcomas: relation to drug resistance and biological aggressiveness.

Human soft tissue sarcomas (HSTS) in adults are a family of mesenchymal tumors characterized by high biological aggressiveness and general refractoriness to chemotherapy. A series of 36 HSTS, 24 untreated and 12 homogeneously treated with a presurgical chemotherapeutic regimen consisting of doxorubicin (intra-arterial) and iphosphamide (intra-vein), was analyzed for expression of MDR1 and the glutathione-S-transferase-pi (GST-pi) gene in order to identify molecular phenomena which may be implicated in the chemoresistance displayed by these tumors. The MDR1 gene was expressed in a greater percentage of drug-treated tumors and at higher levels than in untreated ones. By contrast, chemotherapeutic treatment has no effect on GST-pi mRNA expression. The GST-pi expression level (EL) was much higher in the HSTS with biologically aggressive features. In fact, significant correlations were observed between GST-pi and histologic grade (p = 0.01); aneuploidy (p less than 0.01); and histone H3 EL (p = 0.01), suggesting a possible causal relationship between GST-pi activity and biological aggressiveness in HSTS.

Adult↗
PubMed1992

Association of Epstein-Barr virus genome with mixed cellularity and cellular phase nodular sclerosis Hodgkin's disease subtypes.

Association of Epstein-Barr virus (EBV) genome with Hodgkin's disease (HD) histological subtypes was investigated using the polymerase chain reaction (PCR). A highly significant association of EBV genome with the mixed cellularity (MC) subtype (10 positive out of 15 cases; 66%) was observed, suggesting a possible etiopathogenetic role of EBV in the induction of this subset. By contrast, a markedly lower frequency of association with EBV genome was found in nodular sclerosis (NS) (12 positive out of 46 cases; 26%) and in nodular lymphocytic predominance (NLP) (0 positive out of 5 cases) HD subtypes. In addition, in the NS series, the presence of EBV genome was mainly restricted to the 'cellular phase' NS subset. This finding strengthens the possibility, suggested by clinico-pathological features and survival rates, that 'cellular phase NS' is a disease more akin to MC than to typical NS HD.

Genome, Viral↗
PubMed1992

Adhesion molecule expression does not influence the leukemic behavior of murine T-cell lymphomas.

Recirculation and homing properties of normal lymphocytes are controlled by interactions with high endothelial venules (HEVs), specialized vessels which mediate the extravasation into lymphoid tissues. The present study was aimed at elucidating whether lymphoma-derived leukemic cell spreading and peripheral lymph node invasion ability are mediated by the recognition mechanisms which physiologically regulate normal lymphocyte trafficking. For this purpose, we tested the HEV-binding ability and the expression of the lymphocyte homing receptor (LHR) for peripheral lymph nodes as well as Pgp-1/CD44, LFA-1 and ICAM-1 adhesion molecules by the highly leukemic cell line NQ22 in comparison with a series of non-leukemic murine T-lymphoma cell lines. Our results indicate that the hematogenous spreading as well as peripheral node invasion of lymphoma-derived leukemic cells may occur independently of LHR expression. In addition, our findings seem to rule out that gross quantitative modifications in LFA-1 or ICAM-1 antigen expression are associated with differential dissemination abilities of transformed lymphoid cells.

Animals↗
PubMed1992

High frequency of p53 gene alterations associated with protein overexpression in human squamous cell carcinoma of the larynx.

A series of 58 primary human squamous cell carcinomas of the larynx (LSCCs) was examined for the expression of the p53 tumor-suppressor gene by a combined immunohistochemical and molecular approach. About 60% of the cases displayed nuclear p53 overexpression as revealed by immunostaining with PAb1801, PAb122 and PAb240 monoclonal antibodies. This phenomenon was associated with the presence of structural and/or transcriptional alterations of the p53 gene. Our results provide evidence that p53 abnormalities constitute the most frequent genetic alteration identified so far in LSCC and indicate that the abnormal accumulation of the protein correlates with the presence of p53-mutated versions. These findings, taken together with the peculiar biochemical properties of p53, support the hypothesis of a possible pathogenetic relationship between smoke carcinogen exposure and p53 inactivation in the development of this tumor type.

Antibodies, Monoclonal↗