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E Campo

Publications and source records attributed to E Campo.

At least 127 records · Page 7Linked to original sources

Expression of retinoblastoma gene product (pRb) in mantle cell lymphomas. Correlation with cyclin D1 (PRAD1/CCND1) mRNA levels and proliferative activity.

Mantle cell lymphomas (MCLs) are molecularly characterized by bcl-1 rearrangement and constant cyclin D1 (PRAD-1/CCND1) gene overexpression. Cyclin D1 is a G1 cyclin that participates in the control of the cell cycle progression by interacting with the retinoblastoma gene product (pRb). Inactivation of the Rb tumor suppressor gene has been implicated in the development of different types of human tumors including some high grade non-Hodgkin's lymphomas. To determine the role of the retinoblastoma gene in the pathogenesis of MCLs and its possible interaction with cyclin D1, pRb expression was examined in 23 MCLs including 17 typical and 6 blastic variants by immunohistochemistry and Western blot. Rb gene structure was studied in 13 cases by Southern blot. Cytogenetic analysis was performed in 5 cases. The results were compared with the cyclin D1 mRNA levels examined by Northern analysis, and the proliferative activity of the tumors was measured by Ki-67 growth fraction and flow cytometry. pRb was expressed in all MCLs. The expression varied from case to case (mean, 14.1% of positive cells; range, 1.3 to 42%) with a significant correlation with the proliferative activity of the tumors (mitotic index r = 0.85; Ki-67 r = 0.7; S phase = 0.73). Blastic variants showed higher numbers of pRb-positive cells (mean, 29%) than the typical cases (10%; P < 0.005) by immunohistochemistry and, concordantly, higher levels of expression by Western blot. In addition, the blastic cases also had an increased expression of the phosphorylated protein. No alterations in Rb gene structure were observed by Southern blot analysis. Cyclin D1 mRNA levels were independent of pRb expression and the proliferative activity of the tumors. These findings suggest that pRb in MCLs is normally regulated in relation to the proliferative activity of the tumors. Cyclin D1 overexpression may play a role in the maintenance of cell proliferation by overcoming the suppressive growth control of pRb.

Aged↗

p53 expression in normal, dysplastic, and neoplastic laryngeal epithelium. Absence of a correlation with prognostic factors.

p53 expression has been examined in 89 squamous cell carcinomas of the larynx (34 glottic, 28 supraglottic, 18 transglottic, 8 pyriform sinus, and 1 subglottic) obtained from 88 patients surgically treated in our centre. In addition, 59 laryngeal samples including normal respiratory epithelium and non-invasive squamous cell lesions were also tested. Frozen sections were immunostained with PAb 1801 and the results were correlated with pathological features, DNA ploidy and S-phase of the tumours, disease-free interval, and survival of the patients. p53 immunoreactivity was observed in 57 (64 per cent) carcinomas. None of the eight samples of normal respiratory epithelium was positive. p53-positive cells were seen in 8 of 23 (35 per cent) squamous cell metaplasias, 6 of 19 (32 per cent) low-grade dysplasias and 5 of 10 (50 per cent) high-grade dysplasias. No correlation was found between p53 expression in carcinomas and their clinical and pathological characteristics, DNA ploidy, or proliferative activity. Neither disease-free nor overall survival showed differences between p53-positive and p53-negative cases. These findings indicate that p53 may play a role in an early stage of malignant transformation of a subset of squamous cell carcinomas of the larynx, but seems not to be associated with further progression of the tumours.

Adult↗

Short-term outcome analysis of a randomized study comparing laparoscopic vs open colectomy for colon cancer.

The authors examined the impact of the laparoscopic approach on the early outcome of resected colon carcinomas. The role of laparoscopic techniques in the treatment of colon carcinomas is questionable. Previous studies have suggested technical feasibility of surgical resections of these cancers by laparoscopic means and have implied a benefit to laparoscopic technique for patients undergoing colorectal resections. A prospective, randomized study was conducted comparing laparoscopic assisted colectomy (LAC) open colectomy (OC) for colon cancer. We present the preliminary results in relation to the short-term outcome and judge the feasibility of the laparoscopic procedure to as a way of performing accurate oncologic resection and staging. Benefit has been demonstrated with LAC in this setting. Passing flatus, oral intake, and discharge from hospital occurred earlier in LAC- than OC-treated patients. The mean operative time was significantly longer in the LAC group than in the OC group. The overall morbidity was significantly lower in the LAC group. No significant differences were observed between both groups in the number of lymph nodes removed or the pathological stage following the Astler-Coller modification of the Dukes classification. The laparoscopic approach improves the short-term outcome of segmental colectomies for colon cancer. However, the further follow-up of these patients will allow us to answer in the near future whether or not the LAC may influence the long-term outcome.

Adenocarcinoma↗

Schistosomiasis: an unusual cause of tubal infertility.

A case report of a Nigerian woman having an unusual cause of tubal infertility is presented. On histological examination of the Fallopian tube, ova of Schistosoma haematobium enclosing living miracidia were found in the smooth muscle layer of the Fallopian tube and its mesosalpinx. Mechanisms of tubal involvement are analysed. The case indicates the need to consider schistosomiasis as a possible aetiological factor in patients with tubal infertility coming from areas where the disease is endemic.

Adult↗

Increased expression of the PRAD-1/CCND1 gene in hairy cell leukaemia.

The PRAD-1/CCND1 gene encodes Cyclin D1, a cyclin involved in cell cycle regulation at the G1-S transition. Over-expression of this gene is a highly specific molecular marker of mantle cell lymphomas (MCLs), but it may also be up-regulated in some chronic lymphoproliferative disorders, mainly chronic lymphocytic leukaemia. We have examined PRAD-1/CCND1 gene expression by Northern blot and Western blot analysis in a series of 18 hairy cell leukaemias (HCLs), nine other splenic malignant lymphoproliferative disorders, and three normal/reactive spleens. Over-expression of the mRNA PRAD-1/CCND1 gene was observed in 16/18 HCLs, including one case of hairy cell leukaemia variant, whereas this molecular alteration was not found in other cases examined. mRNA levels varied from case to case, but they were lower than those observed in MCLs. At the protein level, Western blotting analysis showed Cyclin D1 protein expression in the 11 HCLs analysed. No bcl-1 rearrangements were seen with the MTC, p94PS and PRAD-1 (lambda-P1-4) probes used, and no PRAD-1/CCND1 gene amplification was detected in any case. These findings indicate that PRAD-1/CCND1 is over-expressed at mRNA and protein levels in a high number of HCLs. However, the levels of expression are much lower than in MCLs, and this expression is not associated with bcl-1 rearrangements or PRAD-1/CCND1 gene amplification.

Blotting, Northern↗

Mucosal mantle cell (centrocytic) lymphomas.

The morphology, phenotype, genotype and clinical behaviour of four cases of mantle cell lymphoma (centrocytic lymphoma) presenting primarily in mucosa (two gastric, one in large bowel and one tonsillar) are reviewed. Their relationship with the broader group of mantle cell and mucosa-associated lymphoid tissue (MALT) lymphomas is also discussed. All four tumours showed a monomorphic picture of mantle cells (centrocytes) arranged in a diffuse, or vaguely nodular, pattern. Scattered non-neoplastic germinal centres were entrapped within the tumour cells, although there was no follicular colonization. In two cases distinct epithelial infiltration by tumour cells was observed. All four tumours had a CD19, CD20, CD5, IgD, Leu8 immunophenotype, whereas KiM1P and CD10 expression were absent. DRC antibody showed loose aggregates of dendritic cells in three of four cases. Three cases showed PRAD-1/Cyclin D1 overexpression by Northern blot analysis. Although we were not able to detect bcl-1 rearrangement in the major translocation cluster (MTC) breakpoint, the possibility of bcl-1 rearrangement involving other cluster breakpoints cannot be ruled out. The four cases evolved as a disseminated disease, involving either peripheral lymph nodes, spleen or bone marrow. The biological behaviour of mantle cell lymphoma presenting in mucosa appears, irrespective of localization or macroscopic presentation, similar to that of nodal mantle cell lymphoma. Their tendency to dissemination contrasts with MALT lymphomas, which tend to remain localized, and from which mucosa mantle cell lymphoma must be distinguished. The presence of lymphoepithelial lesions does not seem to be a useful differential feature, since occasional epithelial infiltration was seen in two cases. Reactivity with CD5 appears to be especially useful in distinguishing these, since all four cases were clearly positive, in contrast with what is usually found in MALT lymphomas.

Aged↗

Presenting features, natural history, and prognostic factors in localized non-Hodgkin's lymphomas: analysis of 117 cases from a single institution.

Clinical features and prognostic factors were analyzed in a series of 117 patients with localized non-Hodgkin's lymphoma (stage I-II). Median age of the patients was 53 years and 52% were men; 22% had a lymphoma of low-grade histology and one-third presented with extranodal involvement. Eighty percent of the patients achieved a complete response (CR); stage of disease and histology were revealed as the most important factors for response. When analysis was restricted to intermediate/high-grade cases, stage showed a predictive value for response. With a median follow-up of 4.5 years, median overall survival was 12.0 years, with 73% and 62.5% of patients being alive at 5 and 10 years, respectively. Main initial parameters significantly related to a shorter survival were intermediate/high-grade histology, stage II, poor performance status, bulky disease, high serum LDH levels, increased ESR, and advanced International Index. In the multivariate analysis, stage, histology and performance status (PS) were statistically significant. Among intermediate/high-grade lymphoma patients, stage and PS provided prognostic value for survival. Twenty-six patients relapsed after CR; median survival after relapse was 2.7 years. Stage (I vs II) was the only predictive variable for relapse in both the whole series and the intermediate/high-grade subset.

Actuarial Analysis↗

Deletions in the Epstein-Barr virus latent membrane protein-1 oncogene in Hodgkin's disease.

Aims-To analyse the latent membrane protein-1 (LMP-1) gene in a series of patients with Epstein-Barr virus (EBV) positive LMP expressing ordinary and HIV associated Hodgkin's disease to detect possible genetic alterations and particularly the existence of deletions near the 3' end of the gene.Methods-Expression of the EBV LMP-1 was assessed using immunohistochemistry in 186 cases of Hodgkin's disease and 31 cases of HIV associated Hodgkin's disease. Genomic DNA was extracted from frozen lymph node biopsy specimens from 25 cases of Hodgkin's disease and 11 of HIV associated Hodgkin's disease, all of whom expressed the LMP-1 protein within diagnostic Hodgkin and Reed-Sternberg (HRS) cells, and amplified by polymerase chain reaction (PCR) using primers specific for the different LMP-1 regions.Results-LMP-1 expression was observed in 106 of 186 Hodgkin's disease cases and in all 31 HIV associated Hodgkin's disease cases. Molecular analysis of the LMP-1 gene showed a high degree of genetic heterogeneity in the carboxy-terminal domain compared with the prototype B95-8 EBV strain, specially in the patients with HIV associated Hodgkin's disease. Variation in the size of the repeated region was found in 17 of 25 Hodgkin's disease and nine of 11 HIV associated Hodgkin's disease cases. Deletions of 30 base pairs near the 3' end of the gene were detected in all cases of HIV associated Hodgkin's disease and in six Hodgkin's disease. In one case of Hodgkin's disease a larger deletion was observed. In all patients with LMP-1 deletion mutants, 50-90% of the diagnostic HRS cells expressed the LMP-1 protein.Conclusions-The presence of the 30 base pair deletion in all cases of HIV associated Hodgkin's disease supports previous studies that reported aggressive histological and clinical behaviour in tumours harbouring this deletion. This deletion may prolong the half-life of the protein which would explain the high levels of LMP-1 expressing HRS cells in those cases carrying LMP-1 deletions. That the 30 base pair deletion was present in all of the HIV associated Hodgkin's disease specimens suggests that impairment of immune function is a stringent requirement for the expansion of malignant cells infected by EBV strains containing the deleted LMP-1 gene.

Journal Article↗

Splenic marginal zone lymphoma: a distinctive type of low-grade B-cell lymphoma. A clinicopathological study of 13 cases.

The recognition and classification of the different varieties of splenic low-grade B-cell lymphomas have been hampered by the rarity of histological studies of surgical splenectomy specimens of B-cell lymphoma. In an effort to characterize the recently described splenic marginal zone lymphoma (SMZL), we conducted a survey of 13 patients with this type of tumor using the criteria defined by Schmid for its recognition (Schmid et al., Am J Surg Pathol 1992;16:455-66). Primary splenic high-grade lymphomas, T-cell lymphomas, and secondary infiltration by other recognized low-grade B-cell lymphomas, with the exception of splenic lymphoma with villous lymphocytes, were excluded. This selection gave rise to a homogeneous group of tumors with similar clinical, histological, immunohistochemical, and molecular features. Our study showed the critical parameters for their recognition to be morphological, including macroscopic micronodularity and the constant presence of white- and red-pulp infiltration, marginal zone pattern, and plasmacytic differentiation. No t(14;18) or PRAD-1/cyclin D1 overexpression was detect able in any case. Clinically, the tumors were widespread with a protracted evolution. Nodal infiltration by SMZL in our cases was morphologically similar to monocytoid B-cell lymphoma. SMZL could constitute the largest group of primary splenic malignant lymphomas, partially overlapping with splenic lymphoma with villous lymphocytes. Specific molecular markers for SMZL have yet to be defined. Because of the limited number of cases, the question of therapy for this group of lymphomas must remain open for the future.

Aged↗

Leukemia after true histiocytic lymphoma: another type of acute monocytic leukemia with histiocytic differentiation (AML-M5c)?

The case of a 44-year-old man diagnosed of a true histiocytic lymphoma who, after autologous bone marrow transplantation, developed leukemia with histiocytic cells is reported. Morphologic, cytochemical, immunophenotypic and genotypic characteristics of malignant cells are described, and the literature about this and related entities is reviewed. In addition, comparison with a recent report of malignant histiocytosis with leukemic involvement is established and its inclusion in the recently proposed subtype of monocytic leukemia with histiocytic differentiation (M5c), suggested.

Adult↗

Fibrillary glomerulonephritis and pulmonary hemorrhage in a patient with renal transplantation.

Fibrillary glomerulonephritis is an unusual kidney disease characterized by the deposition of immunoglobulins in a fibrillar pattern. Until recently it has been considered to involve the kidneys alone. We describe a patient who underwent renal transplantation and developed fibrillary glomerulonephritis with rapidly progressive renal failure and severe pulmonary hemorrhage two years and a half after transplantation. Nephropathy prior to transplantation was thought to be focal and segmental glomerulosclerosis. Diagnosis of fibrillary glomerulonephritis in renal allograft was confirmed by postmortem examination. 50% of the glomeruli with extracapillary crescents were observed on light microscopy. By immunofluorescence main deposition of IgA was detected in the glomerular capillar walls and the mesangium. Electron microscopy showed fibrillo-reticular deposits in the same place. Lung histology showed both old and recent areas of alveolar hemorrhage. Granular staining for IgA was observed in the alveolar walls by immunofluorescence. Ultrastructural analysis of the lung made evident fibrillo-reticulary deposits in the interstitium, similar than those observed in the glomeruli. The presence of these deposits in both renal and pulmonary tissues indicates the possibility of systemic involvement in fibrillary glomerulonephritis. In our case it could be related to the recurrence of this glomerulopathy in renal allograft.

Fatal Outcome↗

Lipolytic effects of beta1, beta2 and beta3-adrenergic agonists in isolated human fat cells from omental and retroperitoneal adipose tissues.

The presence of beta1- and beta2-adrenoceptors has been clearly established in human fat cells. There is some controversy about the presence and function of beta3-adrenoceptors. It is well established that there are marked regional variations in catecholamine-induced lipolysis. In this work the possibility that a beta3-adrenoceptor plays a significant role in the control of lipid mobilization is studied and also its importance in comparison to beta1- and beta2-adrenoceptors in isolated human fat cells, is evaluated, by measuring the in vitro lipolysis induced by dobutamine, salbutamol, metaproterenol, BRL 37344 and CGP 12177A. Human adipocytes from omental and retroperitoneal fat deposits exhibited an "atypical" beta-adrenergic response but, given the small lipolytic effect initiated by BRL 37344 and CGP 12177A, they are probably poorly equipped in functional beta3-adrenoceptors.

Adipose Tissue↗

PRAD-1/cyclin D1 gene overexpression in chronic lymphoproliferative disorders: a highly specific marker of mantle cell lymphoma.

The t(11;14)(q13;q32) translocation and its molecular counterpart bcl-1 rearrangement are frequently associated with mantle cell lymphomas (MCLs) and only occasionally with other variants of B-cell lymphoid malignancies. This translocation seems to activate the expression of PRAD-1/cyclin D1 gene located downstream from the major breakpoint cluster region of this rearrangement. However, the possible overexpression of this gene in other lymphoproliferative disorders independently of bcl-1 rearrangement is unknown. We have examined the overexpression of PRAD-1 gene in a large series of 142 lymphoproliferative disorders including 20 MCLs by Northern blot analysis. Cytogenetic and/or bcl-1 rearrangement analysis with 2 probes (MTC, p94PS) were performed in 28 cases. Strong PRAD-1 overexpression was observed in 19 of the 20 MCLs including 3 gastrointestinal forms and 4 blastic variants. t(11;14) and/or bcl-1 rearrangement was detected in 6 of the 12 MCLs examined. No correlation was found between the different levels of mRNA expression and the pathologic characteristics of the lymphoma. Among chronic lymphoproliferative disorders other than MCL, only 1 atypical chronic lymphocytic leukemia (CLL) with a t(11;14) translocation and bcl-1 rearrangement and the 2 hairy cell leukemias (HCLs) analyzed showed upregulation of PRAD-1 gene. The expression in the 2 HCLs was lower than in MCL, and no bcl-1 rearrangement was observed. These findings indicate that PRAD-1 overexpression is a highly sensitive and specific molecular marker of MCL but it may also be upregulated in some B-CLLs and in HCL.

Biomarkers, Tumor↗

PRAD-1/cyclin D1 gene amplification correlates with messenger RNA overexpression and tumor progression in human laryngeal carcinomas.

PRAD-1 is a putative oncogene localized on chromosome 11q13 which encodes cyclin D1, a novel cyclin involved in cell cycle regulation. Amplification of this gene has recently been reported in several human tumors including breast and head and neck carcinomas. In this study we have analyzed the presence of PRAD-1/cyclin D1 gene amplification and mRNA overexpression in a series of 46 matched normal mucosas and squamous cell carcinomas of the larynx. PRAD-1/cyclin D1 was found to be amplified 2- to 12-fold in 17 carcinomas (37%). DNA amplification correlated with advanced local invasion (P = 0.0015), presence of lymph node metastases (P = 0.0078), and stage IV of the tumors (P = 0.0021). mRNA overexpression was found in 15 of the 43 (35%) cases examined and it was also significantly associated with advanced local invasion (P = 0.0025) and stage IV carcinomas (P = 0.0032). A significant association was observed between gene amplification and mRNA overexpression (P < 0.0001) with only 3 discordant cases (2 amplifications with no overexpression and 1 overexpressed carcinoma with no gene amplification). Furthermore, the degree of DNA amplification correlated with the levels of mRNA expression (r = 0.6; P = 0.024). These findings suggest that the PRAD-1/cyclin D1 gene may be an important target of 11q13 amplifications in laryngeal carcinomas and the activation of this gene may be involved in the progression of these tumors. Its association with advanced-stage tumors indicates that PRAD-1/cyclin D1 gene amplification and overexpression may be of prognostic significance.

Adult↗

Prognostic significance of the loss of heterozygosity of Nm23-H1 and p53 genes in human colorectal carcinomas.

BACKGROUND: Nm23 is a gene associated with low tumor metastatic potential and has been proposed to be a metastasis suppressor gene. Nm23 is localized on chromosome 17q21.3-22, whereas the p53 suppressor gene is on 17p13. Allelic deletions of chromosome 17 have been related to the progression of colorectal carcinomas. The purpose of this study was to analyze the allelic deletions of Nm23 and p53 in colorectal carcinomas and to assess their prognostic significance in the evolution of the patients. METHODS: Allelic deletions of Nm23 and p53 genes were studied in 56 colorectal carcinomas using different restriction fragment length polymorphisms. DNA ploidy and proliferative activity of the tumors were studied by flow cytometry. Actuarial disease free and overall survival were analyzed by the Kaplan--Meier method, and the curves were compared with the log rank test. RESULTS: Thirty-eight patients were heterozygous for Nm23 gene (68%), and 9 of them (24%) exhibited a loss of heterozygosity in the tumor sample. One of the homozygous patients showed a loss of both Nm23 alleles. Allelic deletions of 17p13 were found in 63% of the 41 informative patients. All patients' tumors that had loss of heterozygosity of the Nm23-H1 locus also had allelic losses on the short arm of chromosome 17 (17p13) and in other loci on 17q. No relationship was found between localization, invasion, lymph node metastasis, or proliferative index of the tumors and the allelic deletions of the Nm23-H1 or 17p13 locus. Nm23-H1 deletions were relatively more frequent in poorly differentiated adenocarcinomas (P = 0.03). A significant association between 17p13 deletions and DNA aneuploidy was found (P = 0.016). A similar tendency was observed with Nm23-H1 deletions (P = 0.051). Loss of Nm23-H1, but not of 17p13, was significantly associated with a shorter disease free (P = 0.025) and overall (P = 0.04) patient survival. CONCLUSIONS: Allelic deletions of Nm23-H1 are significantly associated with a more aggressive behavior of colorectal carcinomas. The loss of this gene seems to be part of extensive deletions of chromosome 17, and it is also associated with DNA aneuploidy. More studies are needed to determine whether Nm23-H1 or a gene linked to this locus is the specific target of the progression of these tumors.

Adenocarcinoma↗

Immunohistochemical characterization of inflammatory cells and immunologic activation markers in muscle and nerve biopsy specimens from patients with systemic polyarteritis nodosa.

OBJECTIVE: To investigate the phenotype of infiltrating cells in classic lesions of polyarteritis nodosa (PAN). METHODS: Twenty-one muscle and 10 sural nerve biopsy samples from 24 patients with systemic PAN were studied using avidin-biotin-peroxidase and alkaline phosphatase-anti-alkaline phosphatase immunohistochemical techniques. RESULTS: The inflammatory infiltrates consisted mainly of macrophages (41%) and T lymphocytes (41%), particularly of the CD4+ subset. Granulocytes were present in varying quantities (0-45%) and were more abundant in heavily infiltrated vessels and in those with fibrinoid necrosis. Dendritic cells could be identified in 4 samples. Proliferating and interleukin-2 receptor-expressing cells, present in 71% and 79% of the patients, respectively, were more frequent in untreated patients. CONCLUSION: T cell-mediated immune mechanisms may play a role in the development and perpetuation of PAN lesions.

Adult↗