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E Pescarmona

Publications and source records attributed to E Pescarmona.

At least 37 records · Page 2Linked to original sources
PubMed1999

Clinical characteristics and outcome of young chronic lymphocytic leukemia patients: a single institution study of 204 cases.

A retrospective analysis on chronic lymphocytic leukemia (CLL) patients </=55 years observed at a single institution was performed with the purpose of characterizing the clinical features and outcome of young CLL and of identifying patients with different prognostic features. Over the period from 1984 to 1994, 1,011 CLL patients (204 [20%] </=55 years of age and 807 [80%] >55 years of age) were observed. At diagnosis, younger and older patients displayed a similar distribution of clinical features, except for a significantly higher male/female ratio in younger patients (2.85 v 1. 29; P <.0001). Both groups showed an elevated rate of second primary cancers (8.3% v 10.7%), whereas the occurrence of Richter's syndrome was significantly higher in younger patients (5.9% v 1.2%; P <. 00001). Younger and older patients showed a similar overall median survival probability (10 years) but were characterized by a different distribution of causes of deaths: CLL unrelated deaths and second primary malignancies predominated in the older age group, whereas the direct effects of leukemia were prevalent in the younger age group. Although younger and older patients displayed a similar survival, the evaluation of the relative survival rates showed that the disease had a greater adverse effect on the expected survival probability of the younger population. Multivariate analysis showed that for young CLL patients only dynamic parameters, such as lymphocyte doubling time and other signs of active disease, were the independent factors that significantly influenced survival probability (P =.00001). A prolonged clinico-hematologic follow-up allowed us to identify two subsets of young CLL patients with a different prognostic outcome: a group of patients (40%) with long-lasting stable disease without treatment and an actuarial survival probability of 94% at 12 years from diagnosis and another group (60%) with progressive disease and a median survival probability of 5 years after therapy. For the latter patients, the therapeutic effect of innovative therapies with curative intents needs to be investigated in prospective, comparative clinical trials.

Adult↗
PubMed1999

The role of high resolution pulsed and color Doppler ultrasound in the differential diagnosis of benign and malignant lymphadenopathy: results of multivariate analysis.

BACKGROUND: The role of high resolution pulsed and color Doppler ultrasound in the differential diagnosis of benign and malignant lymphadenopathy is still unclear. METHODS: High resolution pulsed and color Doppler ultrasound was used prospectively to investigate superficial lymph node enlargement in 71 patients undergoing surgical biopsy at the onset of lymphadenopathy. The aim of this study was to define, in multivariate analysis, the ultrasonographic parameters useful in the differential diagnosis of benign and malignant lymphadenopathy. RESULTS: Volume, vascularization score, pulsatility index, and resistive index were significantly higher in the 53 malignant lymph nodes studied than in the 18 benign lymph nodes studied. The long-to-short axis ratio was significantly lower in neoplastic lymph nodes than in reactive lymph nodes. Stepwise logistic regression selected only the long-to-short axis ratio and the vascularization score as parameters that independently and significantly contributed to the differentiation of neoplastic from reactive lymph nodes. The diagnostic efficiency of the combined criteria evaluated by the area under the receiver operating characteristic curve was 0.8339. CONCLUSIONS: High resolution pulsed and color Doppler ultrasound may provide information that is useful in making correct differential diagnoses of malignant or benign lymphadenopathy.

Adolescent↗
PubMed1999

Expression of p53 and retinoblastoma gene in high-grade nodal peripheral T-cell lymphomas: immunohistochemical and molecular findings suggesting different pathogenetic pathways and possible clinical implications.

The expression of p53 and the retinoblastoma gene has been investigated by immunohistochemical and molecular analysis in 45 cases of nodal peripheral T-cell lymphoma with high-grade histology. Most cases (73.3 per cent) were primary nodal lymphomas without any extra-nodal site involvement. Most of them (75.6 per cent) were histologically classified as pleomorphic, small, medium, and large cell type. Immunohistochemistry detected p53 in nine cases (20 per cent). In each of these cases, the polymerase chain reaction (PCR)/heteroduplex analysis did not show the presence of mutations, this finding being consistent with an alteration of the p53 functional pathway, in the presence of a wild-type protein. The retinoblastoma gene product was detected by immunohistochemistry in 35 cases (77.8 per cent) and not detected in ten cases (22.2 per cent). In the latter cases, the reverse transcription (RT)-PCR analysis showed the presence of a specific retinoblastoma gene transcript in six cases and was negative in the remaining four cases. The immunohistochemical and molecular findings seem to be consistent with abnormalities of retinoblastoma gene expression at either the transcriptional or the post-transcriptional level. Since all nine p53-positive cases by immunohistochemical analysis were also retinoblastoma gene product-positive, and all ten retinoblastoma gene product-negative cases were also p53-negative, two different and mutually exclusive pathways of possible pathogenetic significance may be suggested, the former involving abnormalities of the functional pathway of p53 in the absence of mutations and the latter abnormalities of retinoblastoma gene expression at the transcriptional and/or post-transcriptional level. Finally, the clinico-pathological correlations showed that p53 immunohistochemical expression is significantly associated with a poorer response to intensive chemotherapy.

Adolescent↗
PubMed1999

"Composite" lymphoma, lymphoplasmacytoid and diffuse large B-cell lymphoma of the spleen: molecular-genetic evidence of a common clonal origin.

We describe here the first well-characterized case of "composite" lymphoma of the spleen in which the two components were a low-grade and a high-grade B-cell non-Hodgkin's lymphomas. The patient was an elderly man with prominent splenomegaly and multiple hypoechogenic lesions of the spleen. A splenectomy was performed, and the macroscopic and histological findings showed the simultaneous presence of a "low-grade" B-cell lymphoma, lymphoplasmacytoid (immunocytoma) and a "high-grade" B-cell lymphoma (immunoblastic), which were spatially separated. The two lesions expressed the same immunoglobulin light chain (lambda), but the Southern blot analysis showed different patterns of immunoglobulin heavy chain (IgH) clonal rearrangement. PCR analysis followed by direct sequencing of the IgH-amplified rearrangement products provided molecular-genetic evidence that the two components of the composite lymphoma had the same clonal origin. Since both EBV LMP-1 and p53 were negative by immunohistochemistry, it is unlikely that EBV and p53 were involved in the neoplastic progression in this case. PCR analysis and direct sequencing of IgH-amplified rearrangement products are useful tools to investigate clonality in cases in which Southern blot analysis cannot be performed or does not provide conclusive findings.

Aged↗
PubMed1999

Cutaneous involvement in lymphoblastic lymphoma.

Lymphoblastic leukemia/lymphoma (LBL) is a malignant neoplasm of precursor lymphocytes of B- or T-cell phenotype. Involvement of the skin is relatively uncommon. We examined retrospectively the clinicopathologic, immunophenotypic, and molecular genetic features of six patients with cutaneous involvement of LBL (B-LBL=5; T-LBL=1). Patients presented clinically with solitary, large tumors located on the head (3 cases) or the back (1 case), or with generalized tumors (2 cases). Ulceration was uncommon. In two patients the onset of skin lesions was concomitant to the diagnosis of lymphoblastic leukemia. Histopathologic examination showed in all cases a dense, diffuse, monomorphous infiltrate located in the entire dennis and subcutaneous fat. A typical "starry sky" pattern was observed in the majority of the lesions. In some areas neoplastic cells were aligned in a "mosaic-like" fashion. Cytomorphologically, medium sized lymphoid cells with round or convoluted nuclei, inconspicuous nucleoli and scant cytoplasm predominated. There were no significant differences in the histopathologic features of skin lesions in T- and B-LBL. In B-LBL, CD79a was more useful than CD20 in determining the phenotype of neoplastic cells (4/5 cases positive for CD79a as compared to 2/5 cases positive for CD20). TdT, CD10 and CD43 were positive in 4 cases, CD34 in 2. The case of T-LBL revealed positivity for CD1a, CD3, CD43 and TdT, and negativity for CD34 and for B-cell markers. All neoplasms were positive for CD99 and bcl-2, and showed a high proliferation rate. Molecular genetic analysis of J(H) and T-cell receptor (TCR) genes performed using a polymerase chain reaction technique revealed a monoclonal rearrangement of J(H) genes in all five B-LBLs. One of these cases showed also a concomitant TCR-gamma gene rearrangement. A monoclonal rearrangement of the TCR-gamma gene was detected in the case of T-LBL. Our study shows that skin lesions of LBL present characteristic clinicopathologic and molecular features allowing the differentiation from other cutaneous lymphomas, even in cases without clinical history of previous precursor lymphoblastic leukemia/lymphoma.

Adult↗
PubMed1998

MACOP-B and involved field radiation therapy is an effective therapy for primary mediastinal large B-cell lymphoma with sclerosis.

PURPOSE: To evaluate the clinical features of presentation and the response to two different third-generation regimens (F-MACHOP and MACOP-B) of primary mediastinal large B-cell lymphoma (MLBCL), a recently defined distinct clinicopathological entity of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-seven consecutive patients with MLBCL, eight male and 29 female (F/M ratio 1:3.5) with a median age of 35 years, were enrolled in the present study. Thirty-five (94.5%) patients presented disease confined to thorax, with chest symptoms of a rapidly enlarging mass in the mediastinum in 70% and superior vena cava syndrome (SCVS) in 43% of these patients. The first 10 patients received F-MACHOP and the succeeding 27 patients MACOP-B chemotherapy, associated in 24 (88.8%) with involved field radiation therapy (IFRT). 67Gallium scan was routinely performed pre- and post-IFRT in 18 patients. RESULTS: All 37 patients were assessable for response: 10 of 10 (100%) in the F-MACHOP and 26 of 27 (96.3%) in the MACOP-B group achieved overall responses (CR + PR). Three of 24 (12.5%) patients in PR after chemotherapy obtained CR after IFRT. Persistent Gallium avidity was observed in 16 patients after chemotherapy and in only four patients after IFRT. Thus far, four of the 10 F-MACHOP and two of the 26 MACOP-B responders have presented disease progression. The probability of progression-free survival (PFS) was 91% and 60% (P < 0.02) while overall survival (OS) was 93% and 70% (P = n.s.) at a mean follow-up of 27 and 52 months in the MACOP-B + IFRT and F-MACHOP groups, respectively. CONCLUSION: MACOP-B + IFRT has proved to be a highly effective and less toxic therapeutic approach for primary MLBCL and appears to be superior to other third-generation chemotherapy regimens.

Adolescent↗
PubMed1998

Combined modality therapy in advanced Hodgkin's disease: a report on 218 patients with a median follow-up of eight years.

BACKGROUND AND OBJECTIVE: This study was designed to evaluate the efficacy and toxicity of monthly alternating ABVD/MOPP compared to ABVD/OPP regimens in patients with advanced stage Hodgkin's disease (HD), as well as in early stage patients with systemic symptoms and/or bulky disease. DESIGN AND METHODS: 218 patients with previously untreated HD entered this study: 106 patients in arm A (ABVD/MOPP) and 112 in arm B (ABVD/OPP). Patients received eight courses of one of the two regimens after stratification according to the stage. Patients in complete remission (CR) received 20 Gy to the involved field and 40 Gy to the spleen. The actuarial survival curves were performed according to Kaplan and Meier. RESULTS: No statistically significant differences were observed between the two arms in terms of CR rate and toxicity. However, analysis of total relapses revealed that patients treated with ABVD/OPP had a significantly higher likelihood of achieving a second CR compared to patients who entered the ABVD/MOPP arm. INTERPRETATION AND CONCLUSIONS: Both schemes of chemotherapy followed by radiotherapy produce high percentages of CR, low risk of relapse and an acceptable toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Pathogenetic and clinical implications of Bcl-6 and Bcl-2 gene configuration in nodal diffuse large B-cell lymphomas.

Bcl-6 (LAZ-3) and Bcl-2 gene rearrangements have been respectively reported in 20-35 per cent and 10-25 per cent of diffuse large B-cell lymphomas (DLBCLs). Although these genetic lesions have been associated with different clinical outcomes (i.e., more favourable in Bcl-6 rearranged cases and poorer in Bcl-2 rearranged cases), their prognostic significance is still controversial. In the present study, we have investigated by Southern blot analysis the Bcl-6 and Bcl-2 gene configuration in a series of 80 lymph nodes involved by well-characterized DLBCLs, histologically defined according to the REAL and the updated Kiel classifications. The molecular findings have been correlated with the clinical features at presentation and with response to therapy. The majority of cases (57/80 = 71.2 per cent) had a centroblastic morphology. Bcl-6 rearrangements were detected in 23/80 cases (28.8 per cent), and were similarly associated with centroblastic (18/57 = 31.6 per cent) or immunoblastic (3/11 = 27.3 per cent) histotypes. In contrast, Bcl-2 was found to be rearranged in only three cases of centroblastic lymphoma (3.8 per cent). No significant differences were found between Bcl-6 rearranged and germline cases, as far as the clinical features at presentation are concerned. Forty-one patients, in whom the lymph node biopsy was performed at diagnosis, could be evaluated for response to treatment and clinical outcome. Most of these cases (30/41 = 73.2 per cent) were nodal DLBCL, without extranodal site involvement. Analysis of the clinical outcome showed no statistically significant differences between Bcl-6 rearranged and Bcl-6 germline cases (actuarial overall survival 50 per cent vs. 48 per cent, event-free survival 45 per cent vs. 46 per cent, at 4 years). These findings confirm that Bcl-6 rearrangements are the most frequent genetic lesion in DLBCL. The incidence of Bcl-2 involvement in our series is significantly lower than the figures reported in other studies, mainly from North American countries, probably reflecting heterogeneous patient selection and/or epidemiological variability. Finally, our results suggest that no relevant clinical differences are observed between Bcl-6 rearranged and Bcl-6 germline cases, when nodal DLBCLs are considered.

Adolescent↗
PubMed1997

Salvage lung resection for massive hemoptysis after resolution of pulmonary aspergillosis in a patient with acute leukemia.

A 58-year-old woman with acute myelogenous leukemia in complete remission underwent successful pulmonary resection for massive hemoptysis occurring after resolution of pulmonary aspergillosis. Despite the fact that the role of surgery in the treatment of pulmonary mycosis in immunocompromised hosts is still to be clearly defined, emergency lung resections can be successfully performed in this group of patients with almost immediate recovery of stable clinical parameters. Brisk recovery can reduce overall morbidity and mortality and allow for early resumption of any necessary treatment for underlying disease.

Amphotericin B↗
PubMed1996

Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin's disease.

The BCL-6 gene encoding a nuclear-located Kruppel-type zinc finger protein is rearranged in about 30% diffuse large B-cell lymphomas and is expressed predominantly in normal germinal center B cells and related lymphomas. These findings suggest that BCL-6 may play a role in regulating differentiation of normal germinal center B cells and that its deregulated expression caused by rearrangements may contribute to lymphomagenesis. This prompted us to investigate the expression of the BCL-6 protein in Hodgkin's disease (HD), focusing on the nodular lymphocyte predominance subtype (NLPHD), which differs from classical HD by virtue of the B-cell nature of the malignant cell population (so-called L&H cells) and its relationship with germinal centers. Forty-one HD samples (19 NLPHD, 12 nodular sclerosis, and 10 mixed cellularity) were immunostained with the monoclonal antibodies PG-B6 and PG-B6p that react with a fixative-sensitive and a formalin-resistant epitope on the aminoterminal region of the BCL-6 gene product, respectively. Strong nuclear positivity for the BCL-6 protein was detected in tumor (L&H) cells in all cases of NLPHD. In contrast, BCL-6 was expressed only in a small percentage of Hodgkin and Reed-Sternberg cells in about 30% of classical HD cases. Notably, the nuclei of reactive CD3+/CD4+ T cells nearby to and rosetting around L&H cells in NLPHD were also strongly BCL-6+, but lacked CD40 ligand (CD40L) expression. This staining pattern clearly differed from that of classical HD, whose cellular background was made up of CD3+/CD4+ T cells showing the BCL-6-/CD40L+ phenotype. These results further support the concept that NLPHD is an histogenetically distinct, B-cell-derived subtype of HD and suggest a role for BCL-6 in its development.

Animals↗
PubMed1996

Monoclonal antibodies PG-B6a and PG-B6p recognize, respectively, a highly conserved and a formol-resistant epitope on the human BCL-6 protein amino-terminal region.

The human BCL-6 gene, which is rearranged in approximately 30% of diffuse large B cell lymphomas, encodes a 706-amino-acid nuclear protein of the Kruppel-type zinc finger transcription factors mainly expressed in normal germinal center B cells and related lymphomas. Four monoclonal antibodies (PG-B6, PG-B6a, PG-B6p, and PG-B6m), specifically directed against the human BCL-6 protein, were generated by immunizing BALB/c mice with a recombinant protein corresponding to the BCL-6 amino-terminal region (amino acids 3 to 484). The PG-B6 monoclonal antibody reacted with a BCL-6 epitope sensitive to fixatives and preserved in all mammalian species. PG-B6a (a is for avian) recognized the most evolutionarily conserved BCL-6 epitope (expressed in all animal species including avian). PG-B6p (p is for paraffin) recognized a fixative-resistant epitope of BCL-6 that was detectable on paraffin sections after microwave heating in 1 mmol/L EDTA buffer. PG-B6m (m is for mantle) was the least specific monoclonal antibody as, in addition to BCL-6, it reacted with a yet undefined antigen selectively located in the cytoplasm of mantle and marginal zone B cells. All monoclonal antibodies detected strong nuclear expression of BCL-6 in follicular lymphomas, diffuse large B cell lymphomas, Burkitt's lymphomas, and nodular, lymphocyte-predominance Hodgkin's disease. In diffuse large B cell lymphomas, BCL-6 expression was independent of BCL-6 gene rearrangements and did not correlate with expression of other markers or the proliferation index. BCL-6 was not expressed in B-CLL, hairy cell leukemia, mantle-cell- and marginal-zone-derived lymphomas. Labeling of paraffin sections with PG-B6p proved useful for differentiating proliferation centers in B-CLL (BCl-2+/BCL-6-) from trapped germinal centers in mantle cell lymphomas (BCL-2-/BCL-6+) and for identifying neoplastic cells in cases of nodular, lymphocyte-predominance Hodgkin's disease. Because of their high specificity, wide reactivity in humans and animal species including avians (PG-B6a), and suitability for labeling routine paraffin sections (PG-B6p), the reagents described in this paper should prove valuable in both research and diagnostics.

Amino Acid Sequence↗
PubMed1995

Analysis of the BCL-6 gene configuration in diffuse B-cell non-Hodgkin's lymphomas and Hodgkin's disease.

BCL-6 is a novel proto-oncogene that codes for a zinc-finger protein sharing homologies with many transcription factors. It has recently been shown that BCL-6 is involved in chromosome band 3q27 aberrations in non-Hodgkin's lymphomas (NHLs) and BCL-6 rearrangements have been detected in 34-45 per cent of diffuse large cell lymphomas with B immunophenotype. We have studied the BCL-6 gene configuration by Southern blot analysis in 60 cases of B-cell NHL and in 17 cases of Hodgkin's disease (HD). BCL-6 was rearranged in 15/46 (32.6 per cent) diffuse B-large cell lymphomas, mainly with centroblastic morphology, and in 2/11 (18.2 per cent) follicular (centroblastic-centrocytic) lymphomas. Conversely, all cases of HD, including four cases of lymphocyte predominant, nodular type (nodular paragranuloma), had a germline configuration. These findings confirm that BCL-6 is rearranged in a significant percentage of diffuse B-large cell lymphomas, suggesting that this proto-oncogene might have a pathogenetic role in this subset of NHLs, but our preliminary analysis suggests that BCL-6 lesions are not involved in the pathogenesis of HD. However, further investigations using more sensitive techniques are required to confirm these findings.

Blotting, Southern↗
PubMed1995

Mediastinal large B-cell lymphoma: clinical and immunohistological findings in 18 patients treated with different third-generation regimens.

We report on the immunophenotype, clinical findings and response to aggressive chemotherapy of 18 patients with mediastinal large B-cell lymphoma (MLCL). Cases were collected from a series of 286 high-grade non-Hodgkin's lymphomas (HG-NHL) which, in the period September 1988 to August 1991, were enrolled in a prospective multicentre trial designed to compare the MACOP-B and F-MACHOP regimens. Immunostaining on frozen sections revealed a previously unrecognized phenotype, i.e. co-expression of B-cell (CD19, CD20, CD22, Ig-associated dimer) and activation-associated antigens (CD30 and CDw70) in about 60% of MLCL cases; in contrast, the activation-associated antigens CD25 and Ki-27 (unclustered) were consistently negative. This peculiar phenotype may reflect a derivation of the tumour from a subset of thymic activated B cells. Clinically, the patients (median age 31 years; F/M ratio 2.6) presented with bulky mediastinal mass (72%) associated with mediastinal syndrome in > 50% cases; disease was stage IIA in most cases. All 18 patients received aggressive chemotherapy (F-MACHOP 11; MACOP-B 7). Complete response (CR) was achieved in 57.1% of cases treated with MACOP-B. In contrast, the response of the 11 MLCL treated with F-MACHOP was poor (CR 18.2%) as compared to that of the 135 HG-NHL treated with the same regimen during the trial (CR 69.6%). This difference was still statistically significant after adjusting for negative prognostic factors (mediastinal mass > 10 cm plus increased LDH) and suggests that F-MACHOP might not be the most appropriate regimen for this kind of lymphoma.

Adolescent↗
PubMed1995

Recurrent thymoma: evidence for histological progression.

The clinicopathological features of nine cases of recurrent thymomas have been studied. At presentation, all cases were histologically classified as thymomas with cortical differentiation, including predominantly cortical thymoma, cortical thymoma and well-differentiated thymic carcinoma. In five cases the morphological features of the recurrence(s) were suggestive of a histological progression of the tumour from predominantly cortical thymoma to cortical thymoma and/or well-differentiated thymic carcinoma, usually associated with a more advanced clinical stage, the latter indicating a clinical progression. These findings suggest that all types of thymoma with cortical differentiation are histologically and histogenetically related neoplasms, associated with a more aggressive clinical behaviour and a significant risk of recurrence. The overall outcome of patients with recurrent thymoma in this series was poor, since six patients (66.6%) died due to the disease, 2-14 years after the first diagnosis. The clinical implication of our findings is that thymomas with cortical differentiation always need careful follow-up, even in those cases which are not obviously invasive at onset.

Adult↗
PubMed1995

Diagnostic relevance of peripheral blood immunocytochemistry in hairy cell leukaemia.

AIMS--(1) To assess the diagnostic relevance of peripheral blood immunocytochemistry in hairy cell leukaemia (HCL); (2) to compare the immunostaining of bone marrow biopsy specimens with bone marrow and peripheral blood cytospins; (3) to evaluate the sensitivity of the different markers used; (4) to identify the ultrastructural localisation of DBA.44 in HCL variant. METHODS--Immunoenzymatic staining procedures, immunoperoxidase and immunoalkaline phosphatase, were used with a panel of monoclonal antibodies directed to HCL associated antigens. Ultrastructural immunostaining was performed using colloidal gold conjugated antibodies. RESULTS--HCL showed strong cytoplasmic reactivity for CD22, CD25, CD103, DBA.44, kappa, or lambda light chains. Peripheral blood diagnostic hairy cells were found in all the cases with absolute counts ranging from 0.11 x 10(9)/l up to 6.4 x 10(9)/l and values increasing with the size of the spleen. A median of 36.5% of leukaemic cells was found in bone marrow aspirates and 70% in bone marrow trephine specimens. The monoclonal antibodies CD22 and DBA.44 showed the highest and the lowest percentage of positive hairy cells, respectively; this difference was statistically significant (p = 0.0025). Ultrastructural immunolabelling with DBA.44 showed a cytoplasmic membrane localisation of the antigen in one case of HCL variant. CONCLUSIONS--(1) Immunocytochemistry is a useful technique which enhances the accuracy of diagnosis in HCL; (2) peripheral blood immunocytochemistry is recommended because it highlights hairy cells in all cases; (3) CD22 appears to be the most sensitive of the markers tested; (4) ultrastructural analysis is a useful tool in selected cases of HCL variant.

Adult↗
PubMed1995

A specific monoclonal antibody (PG-B6) detects expression of the BCL-6 protein in germinal center B cells.

The BCL-6 gene is frequently involved in translocations occurring at the 3q27 locus and is rearranged in approximately 30% of diffuse large cell lymphomas and in a small fraction of follicular lymphomas. The BCL-6 gene encodes for a Kruppel-type zinc-finger protein, the cell/tissue expression and function of which is unknown. In this study, we describe a new monoclonal antibody (PG-B6) that is specifically directed against a fixative-sensitive epitope on the amino-terminal region of the BCL-6 protein. By immunocytochemical analysis, BCL-6 localizes in the nucleus where PG-B6 staining gives a microgranular/diffuse pattern with exclusion of the nucleoli. The main reactivity of PG-B6 in tonsil and spleen is with the nuclei of germinal center B cells, whereas B cells within the mantle and marginal zones do not express BCL-6. No other lymphoid cells in the tonsil express BCL-6 except for a subset of CD3+/CD4+ intrafollicular and interfollicular T cells. A few lymphoid cells of unknown phenotype express BCL-6 in the thymus. Extra-lymphoid BCL-6 expression includes a weak nuclear positivity of epithelia. In non-Hodgkin's lymphomas, BCL-6 expression parallels that observed in normal lymphoid compartments, eg, expression in germinal center-derived tumors (follicular and diffuse large cell lymphomas), but not in mantle cell and marginal zone lymphomas. In most diffuse large cell lymphomas, the BCL-6 protein is expressed at high levels in cases with or without BCL-6 gene rearrangements. These findings indicate that BCL-6 expression is specifically regulated during B lymphocyte development and suggest that BCL-6 may play a role during B cell differentiation in the germinal center.

Animals↗
PubMed1995

Recombinant interferon-alpha and ursodeoxycholic acid versus interferon-alpha alone in the treatment of chronic hepatitis C: a randomized clinical trial with long-term follow-up.

OBJECTIVES: The purpose of this study was to compare, within a randomized controlled trial, the efficacy of recombinant interferon-alpha in combination with ursodeoxycholic acid versus interferon-alpha alone in the treatment of chronic HCV hepatitis. METHODS: Forty anti-HCV positive chronic hepatitis patients with ALT levels persistently greater than 3 times the upper normal level were randomized to receive either interferon-alpha (6 million units three times/wk for 6 months) plus ursodeoxycholic acid (10 mg/kg/day for 9 months) (n = 20) or interferon-alpha (6 million units three times/wk for 6 months) alone (n = 20). Disease activity was monitored monthly by ALT measurement until 18 months after interferon-alpha cessation. Serum HCV-RNA was measured at baseline and after 6, 9, and 24 months. Liver biopsies (basal and at the 9th month) were evaluated blindly and scored by Knodell's criteria. RESULTS: The probability of full or partial response during interferon-alpha treatment was similar in the two groups. The probability of biochemical relapse (i.e, any persistent return of ALT above normal) after 18-month of posttreatment follow-up was 75% in both the combination and the monotherapy group. Relapse, however, occurred significantly later in the combination than in the monotherapy group (6.6 +/- 5.4 [SD] months and 1.8 +/- 1.6 months after IFN-alpha cessation, respectively, p < 0.02). Severe biochemical relapse (i.e., a persistent ALT elevation greater than 3 times normal) occurred more frequently and earlier (p = 0.05) in patients treated with interferon-alpha (58.3%) than in those receiving the combination therapy (27.3%). The cumulative duration of normalized ALT periods during and after treatment was significantly greater (p = 0.005, chi 2) in patients treated with IFN-alpha + UDCA than with monotherapy (189/354 months vs 136/323 months. Lobular necrosis improved in both groups (p = 0.056 and p = 0.001, respectively), whereas portal inflammation improved (p = 0.009) only in the combination therapy group. Among the 30 patients who were viremic at entry, plasma HCV-RNA was no longer detectable after 6 months in four from the combination group and in five from the monotherapy group, yet all patients but one returned HCV-RNA positive 3 months after interferon-alpha cessation and were still viremic after 18 months. Cox's multiple regression identified the histological degree of posttreatment portal inflammation as the sole positive indicator of relapse. CONCLUSIONS: The combination of interferon-alpha and ursodeoxycholic acid prolongs the efficacy of interferon-alpha alone in chronic hepatitic C by delaying the probability of biochemical relapse and/or by reducing its severity, without affecting HCV viremia.

Adult↗