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

P53 is a tumour suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of cellular growth, regulating the entry of the cell into the S-phase. P53 mutations have been identified in a progressively increasing number of human malignancies. Nuclear p53 protein is usually present in non-tumour cells in minute concentrations, due to its short half-life. In contrast, tumours with p53 mRNA mutations show a higher nuclear protein concentration, detectable by immunohistological techniques, due to stabilization by complexing with other proteins such as heat-shock protein or wild-type p53 protein. Levels of nuclear p53 protein detected by immunohistochemistry with the monoclonal antibody PAb 1801 were measured with the aid of an image analysis system in 83 non-Hodgkin's lymphomas (NHLs) and 13 cases of Hodgkin's disease, as well as in 14 cases of normal thymus, reactive tonsils, and lymphadenitis. High levels of p53 protein (greater than 5 per cent of the cells) were present only in high-grade lymphomas (in the proportion 13/55), with a peak incidence in Burkitt's lymphoma (5/8 cases). Lower levels (less than 5 per cent) of p53 protein were detected in low-grade B- and T-cell lymphomas, as well as in most of the cases of Hodgkin's disease, where p53 protein was selectively present in Hodgkin and Reed-Sternberg cells. In 5/14 reactive tonsils or lymph nodes, occasional p53-positive cells were identified. These results suggest a relationship between levels of p53 protein and the aggressiveness of NHL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:P53 protein expression in lymphomas and reactive lymphoid tissue. 138 24

An increased incidence of malignant lymphomas is common to all types of immunodeficient patients whether they be of the natural or constitutionally occurring type, acquired as in acquired immunodeficiency syndrome (AIDS) or of iatrogenic origin as in organ transplantation. Although there is some degree of heterogeneity, the most characteristic feature of these immunodeficient states is alteration of T-cell cytotoxic function. The malignant lymphomas show a variety of relatively common features, notably: rapid onset following the appearance of the immunodeficient state, a high degree of clinical aggressiveness, and a tendency to present in extranodal sites, particularly the central nervous system (CNS) and gastrointestinal tract. The tumors are almost invariably of B-lymphocytic cell origin and while the histologic classifications reflect some diversity, the vast majority of tumors are described as Burkitt-like or diffuse large cell type. There appears to be a high degree of correlation with a preceding fulminant Epstein-Barr virus (EBV) infection resulting in marked B-cell lymphoproliferation in the absence of effective T-cell control. Initially, the B-cell proliferation is clearly polyclonal and reactive in nature, although as time evolves, there appears to be selection of oligoclonal and even monoclonal cell populations. Such cells are latently infected with EBV and may express EBV nuclear protein two and latent membrane protein, which are characteristically seen in proliferating B-lymphocytes in response to growth transformation by EBV. While desoxyribonucleic acid (DNA) probes may continue to demonstrate multiple lymphoid clonal populations, it is hypothesized that the hyperproliferative state favors genetic alterations which select out a single malignant clone. This transformed clone is evidenced by expression of a translocated, activated c-myc oncogene and decreased evidence of EBV nuclear protein two and latent membrane protein, that is, characteristics of Burkitt's lymphoma. Other large cell malignant lymphoma phenotypes may show similar findings. While most studies have continued to suggest that EBV plays a key role in the development of non-Hodgkin's lymphoma (NHL) of AIDS patients, some recent studies have suggested a less dominant role. Therefore, further exploration of the world of molecular biology will be needed to demonstrate whether other factors, namely additional viruses and/or oncogenes play a similar or significant role in the lymphomas of immunodeficient patients.
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PMID:Malignant lymphomas associated with immunodeficiency states. 218 64

Expression of six proto-oncogenes (fos, myc, myb, Ki-ras, Ha-ras, and N-ras) in 43 cases of non-Hodgkin's lymphoma was analyzed by means of in situ hybridization. Biotinylated DNA probes of the six oncogenes and those of immunoglobulin H (IgH) gene and T-cell receptor beta (TCR beta) chain gene were used. The results of in situ hybridization performed under blind conditions by IgH gene and TCR beta chain gene probes were compatible with those of typing by cell surface markers. The nuclear protein-related proto-oncogenes, fos, myc, and myb, were expressed in about 70% to 80% of all cases regardless of phenotype, histology, or histologic grade. On the contrary, genes of ras family were expressed in more limited numbers of cases except for the Ki-ras gene, which was more frequently expressed by cases of the T-cell immunophenotype with a high malignancy grade. The results of dot hybridization with RNA extracted from some cases were compatible with those of in situ hybridization, further demonstrating the specificity of in situ hybridization.
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PMID:Histologic typing of non-Hodgkin's lymphomas by in situ hybridization with DNA probes of oncogenes. 252 66

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 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

The nuclear export protein chromosome maintenance region 1, found to be elevated in non-Hodgkin's lymphomas, controls localization of critical tumor suppressor proteins. Nuclear localization of tumor suppressor proteins is necessary for their cell surveillance function. However, their nuclear exclusion by chromosome maintenance region 1 renders them ineffective making this nuclear transporter an attractive therapeutic target. We have identified selective inhibitors of nuclear export that lock tumor suppressor proteins in the cell nucleus leading to apoptosis of lymphoid but not normal cells. Our inhibitors induce tumor suppressor protein nuclear retention-dependent growth inhibition and apoptosis in a panel of non-Hodgkin's lymphoma cell lines. Western blot of nuclear protein fraction and confocal microscopy analysis demonstrated retention of major tumor suppressor proteins in the cell nucleus. Co-immunoprecipitation studies showed disruption of the tumor suppressor protein-chromosome maintenance region 1 interaction. Small inhibitor RNA knockdown of two major tumor suppressor proteins, p53 in wild-type protein-53 and protein 73 in mutant-protein-53, abrogated inhibitor activity. Oral administration of related inhibitor at 75 and 150 mg/kg resulted in 65 and 70% tumor reduction, respectively and subcutaneous injections of inhibitor (25 and 75 mg/kg) resulted in 70 and 74% suppression of non-Hodgkin's lymphoma tumor growth with no toxicity; residual tumors showed activation of the protein 73 pathway. Our study verifies chromosome maintenance region 1 as a therapeutic target in non-Hodgkin's lymphoma, indicating that this nuclear export protein warrants further clinical investigations.
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PMID:Selective inhibitors of nuclear export for the treatment of non-Hodgkin's lymphomas. 2400 15

Diffuse large B-cell lymphoma is the most common lymphoid malignancy, as it accounts for approximately one third of all patient cases of non-Hodgkin's lymphoma. Patients with diffuse large B-cell lymphoma have markedly different treatment outcomes, suggesting a need for reliable prognostic factors and novel therapeutic approaches. De novo fatty acid synthesis is an important metabolic driver of tumor in multiple malignancies. In this retrospective study, we analyzed expression of fatty acid synthase (a key enzyme in de novo fatty acid synthesis), Spot 14 (thyroid hormone responsive Spot 14, a nuclear protein that promotes expression of genes involved in fatty acid synthesis), and CD36 (the cell surface channel for exogenous fatty acid uptake) in patients with diffuse large B-cell lymphoma and their clinical significance. We observed that overexpression of fatty acid synthase is negatively associated with overall survival (p=0.001) and progression-free period (p=0.004) in patients with diffuse large B-cell lymphoma. Multivariate analysis showed that fatty acid synthase overexpression is an independent prognostic marker of aggressive clinical course. For the first time, we report CD36 as an independent protective factor in patients treated with rituximab. Thus, fatty acid synthase and CD36 expression may serve as prognostic markers to predict response to treatment and survival in diffuse large B-cell lymphoma patients. Fatty acid synthase may also be a potential therapeutic target in lymphoid malignancies.
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PMID:FASN and CD36 predict survival in rituximab-treated diffuse large B-cell lymphoma. 2593 41