Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proliferating cell nuclear antigen (PCNA/Cyclin) is a 36-kD protein that is present in cycling cells but not in resting cells, and therefore represents a marker of tumor proliferation. Application of anti-PCNA/Cyclin monoclonal antibodies has shown that this protein is localized to the nucleus of cycling cells, with the exception of cells in mitosis, which demonstrate faint cytoplasmic reactivity. Recently, Benjamin and Gown found that Reed-Sternberg cells and variants show nuclear and cytoplasmic staining with anti-PCNA/Cyclin antibody 19A2, and suggested that this feature may be useful in distinguishing Hodgkin's disease from other tumors. This report describes the reactivity of 42 workshop cases that were stained with anti-PCNA/Cyclin antibodies 19A2 and/or PC10. Thirty-three (79%) of the 42 cases showed adequate reactivity to allow for interpretation of staining localization. In the group of reactive cases, 26 (79%) showed nuclear and cytoplasmic staining. The localization of PCNA/Cyclin was compared with the consensus diagnosis in each case. Eighty percent of cases classified as Hodgkin's disease, 67% of cases classified as non-Hodgkin's lymphoma, and 100% of unresolved cases showed both nuclear and cytoplasmic staining. The incidence of cytoplasmic PCNA/Cyclin was not different between Hodgkin's disease and non-Hodgkin's lymphoma in this study.
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PMID:Localization of proliferating cell nuclear antigen (PCNA/Cyclin) in workshop cases of Hodgkin's disease and non-Hodgkin's lymphoma. 136 84

The expression of certain cell cycle regulatory proteins: cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin E, Bcl2 and PCNA was examined in peripheral blood lymphocytes (PBL) from 25 cases of chronic lymphocytic leukemias (CLL) in order to analyze a possible cell cycle involvement of CLL lymphocytes. For comparison, we also studied the expression of these proteins in: 23 samples of non-Hodgkin's lymphoma (NHL) tissue of different histological types, 10 samples of non-neoplastic lymphoid tissue (NLT), non-stimulated PBL (NS-PBL) and PHA-stimulated PBL (PHA-PBL) from three healthy donors. Samples were lysed and proteins were resolved on polyacrylamide gel followed by Western blot. The expression of cdk4 and cyclin E, both known to act in early cell cycle stage, was approximately on the same level in all groups of lymphoid pathology examined. In particular, we found that that 19 out of 24 CLL cases were cyclin E positive and all but one were cdk4 positive, ie they expressed these markers over twice the level of non-stimulated healthy PBL. The cdk1 expression was above the level seen in NS-PBL in 14 (56%) cases, but the average expression was significantly lower than in the other tissues examined, including low-grade lymphomas. Cdk2 expression was comparable in CLL and in low malignancy grade NHL, but weaker than in other NHL and in NLT. Cyclins A and B, normally observed in advanced cell cycle phases, were not seen in any CLL case. The presence of cdk4 and cyclin E in the blood cells of the majority of CLL cases studied, as well as cdk1 and cdk2 in some cases, indicate that the CLL cells are not quiescent, but are blocked in an early stage of the G1 cell cycle phase, and/or that the expression of these proteins is pathologically deregulated.
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PMID:Expression of cell cycle regulatory proteins in chronic lymphocytic leukemias. Comparison with non-Hodgkin's lymphomas and non-neoplastic lymphoid tissue. 764 28

The monoclonal antibody (MAb) Ki-67 detects a nuclear proliferation-associated antigen which corresponds to a non-histone protein with a molecular weight of 395 and 345 kD. Its prognostic relevance has been assessed in both lymphoid and non-lymphoid tumours. The MAb PC10 picks up the proliferating cell nuclear antigen (PCNA), which is a 36 kD nuclear protein associated with the cell cycle. Whereas Ki-67 works only in fresh material, PC10 detects a fixation-resistant epitope of PCNA. Preliminary data have revealed a linear relationship between Ki-67 and PC10 reactivity in normal lymphoid tissue and in non-Hodgkin's lymphomas (NHLs). We applied Ki-67 and PC10 to frozen and routine sections, respectively, from 25 examples of Hodgkin's disease (HD) (14 nodular sclerosis, 6 lymphocyte predominance, 5 mixed cellularity) and 100 NHLs (corresponding to the main varieties of the updated Kiel classification). The results obtained can be summarized as follows: (1) both MAbs gave rise to extremely variable results within the same category of NHLs; (2) most Hodgkin and Reed-Sternberg cells (50-98 per cent) were labelled by the reagents; (3) Ki-67 and PC10 stained a similar ratio of neoplastic cells in 65 and 76 per cent of NHL and HD cases, respectively; in the remaining instances, no correspondence was observed, the PC10-positive elements usually outnumbering the Ki-67-positive ones significantly. These discrepancies, which might be due to low PCNA catabolism and/or PCNA expression by quiescent cells, underline the need for further kinetic and clinico-pathologic studies in order to define the specific relevance of PC10.
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PMID:Comparison between the monoclonal antibodies Ki-67 and PC10 in 125 malignant lymphomas. 809 26

The predictive potential of several proliferation indices for therapeutic outcome was investigated in 55 dogs with spontaneously occurring non-Hodgkin's lymphoma (NHL). Indices included potential doubling time (Tpot), argyrophilic nucleolar organizer region (AgNOR) frequency, and proliferating cell nuclear antigen labeling index (PCNA-LI). All tumors were of intermediate- or high-grade histology as assessed by the Working Formulation, and all dogs presented with disease of advanced clinical stage. All tumors were treated with an identical chemotherapeutic protocol. Tpot determination by a bromodeoxyuridine (BrdU) delayed-biopsy technique was readily applied in the dog. AgNOR frequency and PCNA-LI were easily obtained from archival, formalin-fixed, paraffin-embedded canine tissues. When accounting for all other prognostic variables by employing multivariate analysis, Tpot (p=0.017), and AgNOR frequency (p=0.021), but not PCNA-LI, were predictive of first remission duration. AgNOR frequency (p=0.033) was also predictive of survival time, and the predictive potential of Tpot approached significance (p=0.076). We conclude that Tpot and AgNOR frequency can be used as predictors of outcome in dogs with NHL, and spontaneous NHL in the dog may have significant potential as a model for further characterization of the association between tumor cell kinetics and chemoresponsiveness.
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PMID:Assessment of potential doubling time (Tpot), argyrophilic nucleolar organizer regions (AgNOR), and proliferating cell nuclear antigen (PCNA) as predictors of therapy response in canine non-Hodgkin's lymphoma. 919 21

Cell proliferation is a strong prognostic factor in various malignancies including non-Hodgkin's lymphoma's (NHL). Several methods to evaluate tumour proliferation are available based on immunohistochemical and flow cytometric techniques, but none has been widely accepted for multicenter studies. In the present study 51 samples from patients with haematological disorders were analysed for the expression of proliferating cell nuclear antigen (PCNA) by a previously described flow cytometric approach. S-phase specific PCNA (PCNA-S) as well as growth fraction-associated PCNA (PCNA-tot) expression were evaluated. The mean value for PCNA-S was 9.0% and for PCNA-tot 17,4%. PCNA-S and PCNA-tot correlated strongly to each other (r(s) = 0.969, p < 0.001) and to the S-phase fraction determined by DNA histogram analysis (r(s) = 0.927 and 0.934 respectively, p < 0.001). In 23 cases with NHL in vivo iododeoxyuridine (IdUrd) labelling was performed to assess the labelling index (IdUrd-LI, i.e. S-phase fraction), S-phase duration time (Ts) and potential tumour doubling time (Tpot). IdUrd-Li correlated significantly to both PCNA-S and PCNA-tot (r(s) = 0.704 and 0.622 respectively, p < 0.001 and 0.02). In conclusion, especially the PCNA-S seemed to be a candidate for future larger studies of proliferation related aspects of haematological malignancies.
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PMID:Flow cytometric evaluation of proliferating cell nuclear antigen expression in human hematopoietic malignancies. 909 Sep 58

The expression of p53 and PCNA on deparaffinized sections of tumor was assessed in relation to the International Index and response to chemotherapy. Thirty-five non-Hodgkin's lymphoma (NHL) patients were divided into three groups: aggressive NHL, mantle cell lymphoma (MCL), and low-grade NHL. None of the expressions correlated with the International Index or early response to chemotherapy in any group. In low-grade NHL, none of the patients expressed p53. Only one of three patients with overexpression of p53 showed conformational change and alteration of sequence in exon 7 by PCR-SSCP and DNA sequencing. The results showed that p53 and PCNA staining were not useful for predicting early response to chemotherapy, and that their expressions had no correlation with the International Index.
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PMID:Expressions of p53 and PCNA do not correlate with the international index or early response to chemotherapy in non-Hodgkin's lymphoma. 959 Jan 48

The study was aimed to explore the possible roles of survivin and P63 protein in the development and progression of B cell non-Hodgkin's lymphoma (B-NHL) and their relation with cell apoptosis and proliferation. TdT-mediated dUTP nick end labeling (TUNEL) and immunohistochemistry were used to detect the survivin and P63 protein expression, cell apoptosis and proliferating cell nuclear antigen (PCNA) level in 43 cases of B-NHL and 10 cases of reactive hyperplasia lymphoid (RHL) tissues. The results indicated that the positive rates of survivin and P63 protein expression were 69.8% (30/43) and 82.7% (30/43) respectively. The expression of survivin and P63 protein was 10% (1/10) and 40% (4/10) in RHL tissues of 10 cases. The expression of survivin in aggression B-NHL was higher than that in indolent B-NHL (83.3% vs 46.2%, P < 0.01). The expression of P63 proteins in aggressive B-NHL was higher than that in indolent B-NHL (86.7% vs 76.9%, P > 0.05). Apoptotic index (AI) and proliferation index (PI) correlated positively with expression of survivin (r = 0.429, P < 0.01; r = 0.348, P < 0.01), and so do with expression of P63 proteins (r = 0.451, P < 0.01; r = 0.369, P < 0.05). In addition, AI and PI were positively related (r = 0.598, P < 0.001). It is concluded that survivin may participate in the regulation mechanism of B-NHL cell apoptosis and proliferation, P63 as an oncogene enhances proliferation and takes part in the development of B-NHL. There may be a close relationship between survivin and P63 protein in the regulation of lymphocyte proliferative kinetics.
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PMID:[Expression of survivin and P63 protein in B cell non-Hodgkin's lymphoma and their effects on cell apoptosis and proliferation]. 1749 May 31

Hepatitis C virus (HCV) core protein has been shown to deregulate cell growth and programmed cell death in hepatoma cells, but only minimal informations are available about its possible role on B-lymphoproliferative disorders (LPDs). The aim of our work was to analyze the biological activity of HCV core protein on B-cell proliferation. We established Wil2-ns and Ramos B-cell lines that stably expressed the HCV core protein. Growth curve, thymidine incorporation analysis, as well as the expression of PCNA and activated-ERKs demonstrated that HCV core protein induced an increased growth in both cell lines. Interestingly, the HCV core protein expression determined, in our model, a downregulation of DNp73 and an upregulation of DNp63, which was essential for the maintenance of viral-dependent effects on cell growth. Finally, we have identified phosphoinositide 3-kinase (PI3K) as mediator of HCV core-dependent transcriptional increase of DNp63, which in turn correlated with the increasing of lymphocyte proliferation. In primary B-lymphocytes, derived from HCV-related low-grade non-Hodgkin's lymphoma patients, consistent results were obtained. These findings provide evidence for a possible pathogenetic role played by HCV core protein in HCV-related lymphomagenesis; it could occur through the deregulation of PI3K activity, consequent activation of Akt and overexpression of DNp63.
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PMID:Involvement of PI3K in HCV-related lymphoproliferative disorders. 1765 94

The extent of cell proliferation is an important biological aspect of a tumor cell population that can affect clinical outcome. Besides other well established clinical and histopathological prognostic criteria, cell kinetic data may therefore be of significant prognostic value. This study evaluated the proliferative activity of various grades of non-Hodgkin's lymphoma, by analyzing the expression of the proliferating cell nuclear antigen (PCNA). PCNA is a 36 kD nuclear protein associated with the cell cycle and is directly involved in DNA synthesis during cell proliferation. Our study revealed a good correlation (p=0.000) between PCNA expression and tumor grade. The highest levels of PCNA expression (mean=43%) were seen in the high grade lesions and the lowest (mean=19%) in low grade lesions. These results suggest that PCNA immunostaining may be used to evaluate proliferative index in various grades of NHL, which in turn could be used to monitor response to treatment.
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PMID:Tumor proliferative compartment in non-Hodgkin's lymphoma. 2159 Jan 15

Lymphoma is one of the most common malignancies in dogs. Canine lymphoma is similar to human non-Hodgkin's lymphoma (NHL) with shared clinical presentation and histopathological features. This study reports the construction of a comprehensive gene regulatory network (GRN) for canine diffuse large B-cell lymphoma (DLBCL), the most common type of canine lymphoma, and performs analysis for detection of major functional modules and hub genes (the most important genes in a GRN). The canine DLBCL GRN was reconstructed from gene expression data (NCBI GEO dataset: GSE30881) using the STRING and MiMI interaction databases. Reconstructed GRNs were then assessed, using various bioinformatics programmes, in order to analyze network topology and identify major pathways and hub genes. The resultant network from both interaction databases had a logically scale-free pattern. Gene ontology (GO) analysis revealed cell activation, cell cycle phase, immune effector process, immune system development, immune system process, integrin-mediated signalling pathway, intracellular protein kinase cascade, intracellular signal transduction, leucocyte activation and differentiation, lymphocyte activation and differentiation as major GO terms in the biological processes of the networks. Moreover, bioinformatics analysis showed E2F1, E2F4, PTEN, CDKN1A, PCNA, DKC1, MNAT1, NDUFB4, ATP5J, PRKDC, BRCA1, MYCN, RFC4 and POLA1 as the most important hub genes. The phosphatidyl inositol signalling system, P53 signalling pathway, Rac CycD pathway, G1/S checkpoint, chemokine signalling pathway and telomere maintenance were the main signalling pathways in which the protein products of the hub genes are involved.
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PMID:Reconstruction of canine diffuse large B-cell lymphoma gene regulatory network: detection of functional modules and hub genes. 2567 21


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