Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proliferating cell nuclear antigen (PCNA) and c-myc p62 oncoprotein are two nuclear proteins expressed in proliferating and transformed cells. They can be recognized immunohistochemically in paraffin sections by the monoclonal antibodies PC-10 and c-myc 1-9E10, respectively. On the other hand, nucleolar organizer regions (NORs) are loops of DNA that carry the r-RNA genes and can be visualized in paraffin sections as black dots (AgNORs) using a silver impregnation method. It has been suggested that the mean number of AgNORs may reflect the cellular kinetics of a tumor. We independently examined 200 cases of non-Hodgkin's lymphomas using the monoclonal antibodies PC-10 and c-myc 1-9E10, as well as the AgNOR method. Our study shows a very significant correlation between PCNA, c-myc expression, and AgNOR count on the one hand and histologic grade on the other (P < .001), although a significant overlap among the three grades exists. PC-10, c-myc 1-9E10, and AgNOR scores are all shown to be linearly related, even though significant discrepancies were observed, and the correlation is stronger between PCNA and AgNORs (PCNA v c-myc p62, r = .551; PCNA v AgNORs, r = .746; c-myc p62 v AgNORs, r = .529; P < .001). A remarkable finding is that the intermediate group of lymphomas is heterogeneous as far as the proliferative rate is concerned: diffuse large cell cleaved/non-cleaved lymphomas (category G of the Working Formulation) are characterized by a significantly higher proliferative index, as evidenced by the elevated PCNA, c-myc p62, and AgNOR scores, in comparison with the other types of intermediate-grade lymphomas (P < .001). However, the proliferative rate is lower than that of the high-grade lymphomas (PCNA, P < .05; c-myc p62, P < .001; AgNORs, P < .005). No significant difference exists between B-cell and T-cell lymphomas except for the higher expression of c-myc p62 in intermediate-grade B-cell lymphomas, obviously due to the higher proliferative rate of diffuse large cell lymphomas. Based on our findings, it appears that the combination of PCNA, c-myc p62, and AgNORs provides an accurate estimate of the proliferative rate of non-Hodgkin's lymphomas in paraffin sections. Clinical studies may show whether this information has prognostic value independent of histologic classification. In addition, our results suggest that category G (diffuse large cell) lymphomas may belong to a malignancy grade higher than the intermediate grade, a suggestion consistent with their more aggressive biologic behavior.
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PMID:A comparative assessment of proliferating cell nuclear antigen, c-myc p62, and nucleolar organizer region staining in non-Hodgkin's lymphomas: a histochemical and immunohistochemical study of 200 cases. 768 20

Combinations of cytotoxic drugs, based almost entirely upon the results of empirical clinical trials, are the foundation of the modern management of the non-Hodgkin's lymphomas. While highly effective in the high-grade (particularly pediatric) lymphomas, and able to cure a significant fraction of intermediate-grade lymphomas, it has yet to be proven that patients with low-grade lymphomas can be cured by chemotherapy. Yet even if 100% of patients were potentially curable by chemotherapy, the significant medical cost with respect to both immediate and late toxicity is reason enough to search for radically different approaches to therapy. Of particular appeal is the possibility that therapy might be developed that is targeted to the very genetic lesions that are responsible for the pathogenesis of lymphomas. Such therapy should, by definition, be largely specific for the lymphoma cells, and hence devoid of the major side effects presently encountered. Recent advances in the understanding of the molecular basis of lymphomagenesis have provided sufficient information to begin to develop approaches of this kind. Here, I discuss the prospects for sequence-specific therapy, focusing specifically on antisense oligonucleotides. These short stretches of DNA bind specifically to RNA molecules and prevent their translation. If the targeted RNA molecules are specific to the tumor cells, or derived from pathogenetically relevant viral genomes, such therapy has at least the theoretical possibility of inhibiting tumor cell growth, or even killing tumor cells, without causing significant damage to normal cells.
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PMID:Prospects for the therapeutic use of antisense oligonucleotides in malignant lymphomas. 817 21

Using a silver staining technique, nucleolar organizer region-associated proteins (Ag-NORs) have been studied in paraffin sections of 76 non-Hodgkin's lymphomas, five normal lymph nodes, and five <<reactive>> lymph nodes. The mean number of nucleolar organizer regions per nucleus was 1.19 (SD:0.09) for normal lymphocytes, 3.04 (SD:0.14) for reactive lymph nodes, 2.79 (SD:0.44) for low-grade lymphomas, 6.33 (SD:1.58) for intermediate-grade lymphomas, and 10.53 (SD:1.97) for high-grade lymphomas. There were highly significant differences in Ag-NOR counts among the groups (p < 0.001). The Ag-NOR regions were often observed in nuclei in areas where nucleoli themselves were invisible. It is suggested that this method is useful in diagnostic histopathology and in differentiation of the grade of lymphomas.
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PMID:Nucleolar organizer regions in lymphomas: a quantitative study. 823 51

The mdm-2 protein is a 90-kD protein that forms a complex with the p53 protein, enabling cells from some human neoplasms to overcome the growth-suppressing activity of p53. Most non-Hodgkin's lymphomas lack p53 mutations, and the mechanism of inactivation of tumor suppressive function remains obscure. To assess the role of mdm-2 in lymphomagenesis, 22 cases were evaluated for mdm-2 gene amplification or rearrangement in Southern blots. Localization of the mdm-2 protein was performed on cryostat sections and compared with expression of the p53 gene product. No case exhibited mdm-2 gene amplification or rearrangement, but overexpression of nuclear mdm-2 gene protein product was found in three of six diffuse large cell (B-cell immunoblastic) lymphomas (30-70% of the tumor cells stained). The mdm-2 protein was absent from low- and intermediate-grade lymphomas with the exception of a few cells (5% or less) in four cases. The mdm-2-positive cases stained negative for p53. Southern blot analysis showed that samples overexpressing mdm-2 did not have amplification or rearrangement of the gene. In summary, amplification of the mdm-2 gene does not appear to play a prominent role in the pathogenesis of non-Hodgkin's lymphomas, although overexpression of the protein gene product occurs, particularly in high-grade neoplasms.
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PMID:mdm-2 oncogene expression in non-Hodgkin's lymphomas. 891 43

Intermediate-grade lymphomas are defined by the Working Formulation to include four histologic subgroups: follicular large-cell, diffuse small-cleaved-cell, diffuse mixed small- and large-cell, and diffuse large cell (Groups D, E, F, and G, respectively). [1] These four histologic subtypes were found to have "intermediate" median and overall survival features based on outcome analysis of 1,153 patients with non-Hodgkin's lymphomas. Clinicians, however, have come to "expect" different criteria for intermediate-grade lymphomas. Those criteria include an aggressive growth rate, a high risk of fatality early in the disease course without treatment, and a potential for cure using CHOP chemotherapy (cyclophosphamide [Cytoxan, Neosar], doxorubicin [Adriamycin], vincristine [Oncovin], and prednisone). The expectations are summarized by overall survival graphs demonstrating an initial steep curve, followed by a discernible change in slope, and ending in a relatively flat line or plateau representing the proportion of patients cured. [2] That is, an intermediate-grade lymphoma should be an aggressive disease that is potentially curable with CHOP. In that respect, the Working Formulation is partly successful, but not by design.
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PMID:Management of intermediate-grade lymphomas. 983 Jun 31


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