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)

Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell viability may contribute to cancer by facilitating the insurgence of mutations and by promoting resistance to therapy. Despite the identification of several new apoptosis inhibitors related to bcl-2 or to the baculovirus IAP gene, it is not clear whether apoptosis inhibition plays a general role in neoplasia. Here, we describe a new human gene encoding a structurally unique IAP apoptosis inhibitor, designated survivin. Survivin contains a single baculovirus IAP repeat and lacks a carboxyl-terminal RING finger. Present during fetal development, survivin is undetectable in terminally differentiated adult tissues. However, survivin becomes prominently expressed in transformed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate and breast, in vivo. Survivin is also found in approximately 50% of high-grade non-Hodgkin's lymphomas (centroblastic, immunoblastic), but not in low-grade lymphomas (lymphocytic). Recombinant expression of survivin counteracts apoptosis of B lymphocyte precursors deprived of interleukin 3 (IL-3). These findings suggest that apoptosis inhibition may be a general feature of neoplasia and identify survivin as a potential new target for apoptosis-based therapy in cancer and lymphoma.
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PMID:A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. 925 86

Tumoral cells in Hodgkin lymphoma (HL) display an increased growth fraction and diminished apoptosis, implying a profound disturbance of the cell cycle and apoptosis regulation. However, limitations of molecular techniques have prevented the analysis of the tumor suppressor pathways and cell-cycle checkpoints. Tissue microarray (TMA) is a powerful tool for analyzing a large number of molecular variables in a large series of tumors, although the feasibility of this technique has not yet been demonstrated in heterogeneous tumors. The expression of 29 genes regulating the cell cycle and apoptosis were analyzed by immunohistochemistry and in situ hybridization in 288 HL biopsies using TMA. The sensitivity of the technique was validated by comparing the results with those obtained in standard tissue sections. The results revealed multiple alterations in different pathways and checkpoints, including G1/S and G2/M transition and apoptosis. Striking findings were the overexpression of cyclin E, CDK2, CDK6, STAT3, Hdm2, Bcl2, Bcl-X(L), survivin, and NF-kappaB proteins. A multiparametric analysis identified proteins associated with increased growth fraction (Hdm2, p53, p21, Rb, cyclins A, B1, D3, and E, CDK2, CDK6, SKP2, Bcl-X(L), survivin, STAT1, and STAT3), and proteins associated with apoptosis (NF-kappaB, STAT1, and RB). The analysis also demonstrated that Epstein-Barr virus (EBV)-positive cases displayed a characteristic profile, confirming the pathogenic role of EBV in HL. Survival probability depends on multiple biologic factors, including overexpression of Bcl2, p53, Bax, Bcl-X(L), MIB1, and apoptotic index. In conclusion, Hodgkin and Reed-Sternberg cells harbor concurrent and overlapping alterations in the major tumor suppressor pathways and cell-cycle checkpoints. This appears to determine the viability of the tumoral cells and the clinical outcome.
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PMID:Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays. 1239 83

Survivin is a member of the inhibitor of apoptosis protein (IAP) family and functions both as an apoptosis inhibitor and a regulator of cell division. Survivin overexpression is common in many human tumors and correlates with survival in large cell non-Hodgkin's lymphoma. To evaluate this molecule as a potential therapeutic target in large-cell lymphoma, we evaluated the effect of survivin inhibition both in vitro and in vivo. Using an antisense oligonucleotide (ASO) approach, cell growth was significantly inhibited in the DoHH2, RL and HT lymphoma cell lines. In a lymphoma xenograft model, the development of tumors as well as the growth of established tumors was inhibited in the survivin ASO-treated mice compared to controls. To assess the efficacy of the survivin ASO in combination with other biological agents, we combined the survivin ASO with an anti-CD20 monoclonal antibody, rituximab. The effect of survivin ASO and rituximab in combination was additive in vitro. In vivo, however, suppression of tumor growth with the combination was not significantly superior to controls. We conclude that inhibition of survivin expression is an attractive therapeutic strategy in aggressive non-Hodgkin's lymphomas, and that combining survivin ASO with rituximab may enhance the efficacy of this approach.
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PMID:Inhibition of survivin expression suppresses the growth of aggressive non-Hodgkin's lymphoma. 1474 4

Survivin is a member of the inhibitors from the apoptosis family over-expressed in various human cancers. The aim of the study was to evaluate the expression of survivin in lymph nodes, invaded by non-Hodgkin's lymphomas (nHL) and in lymph nodes reactive hyperplasia. We analysed paraffin sections obtained from 50 patients with nHL and from 13 patients with reactive hyperplasia using, an anti-survivin antibody. There was abundant immunoreactivity cytoplasm in 34/50 (68%) patients with nHL and in only 5/13 (38%) with reactive hyperplasia. Out of the 27 patients with aggressive nHL, 19 (70%) revealed survivin expression in almost all tumour cells. Out of the 23 patients with indolent nHL, 16 (70%) revealed the expression but with lower immunoreactivity score. The study indicates that patients with nHL presented a high level of survivin expression, it was more pronounced in aggressive than in indolent nHL.
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PMID:Survivin expression in lymph nodes, affected by lymphoma and reactive hyperplasia. 1563 81

Classical Hodgkin lymphomas (cHL) have now been recognized as B-cell lymphomas with some exceptional cases of T-cell origin. In recent years, there has been accumulating evidence that Hodgkin and Reed-Sternberg (H/RS) cells, the presumed neoplastic-cell population in cHL, are characterized by a profound disturbance of the cell cycle and apoptosis regulation. The constitutive activation of the nuclear factor (NF)-kappaB pathway, which is considered to be involved in the proliferation and survival of H/RS cells. Moreover, substantial evidence that H/RS cells have defective cell cycle and apoptosis regulation has been provided by studies showing that these cells are characterized, in a large proportion of cases, by alterations of the p53, Rb and p27 tumor suppressor pathways, overexpression of cyclins involved in the G1/S and G2/M transition such as cyclins E, D2, D3, A and B1, overexpression of cyclin-dependent kinases such as CDK1, 2 and 6 and overexpression of anti-apoptotic proteins such as c-FLIP, bcl-xl, c-IAP2, X-linked I4P and survivin. Recent studies suggest that interleukin 13 (IL-13) is an important growth and survival factor in H/RS cells. Furthermore, the Epstein-Barr Virus (EBV), which is present in H/RS cells in about 30-50% of cHL, has been shown to affect the cell cycle and apoptosis regulation in cHL. The present review summarizes data with respect to the cell cycle and apoptosis deregulation in cHL.
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PMID:Cell cycle and apoptosis deregulation in classical Hodgkin lymphomas. 1579 9

Although diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, it is both clinically and morphologically heterogenous. The present study investigates the significance of survivin and a novel monoclonal antibody (MAb), T332, immunohistochemically for predicting the prognoses of DLBCL and its subtypes classified as germinal center B-cell-like type (GCB) and non-GCB type (NGCB) based on the expression profiles of CD10, bcl-6, and MUM1. A total of 60 cases of DLBCL (GCB, n = 22; NGCB, n = 38) were examined for the expression of survivin and T332 antigen. Survivin(+) DLBCL had a significantly worse prognosis (P = 0.01) than survivin(-) cases, as already reported, while survivin(+) GCB or NGCB tended to have poor prognoses (P = 0.06 and 0.07, respectively). However, T332(+) DLBCL and NGCB had significantly more unfavorable prognoses than T332(-) cases (P = 0.01 and 0.02, respectively) while there was no significant survival difference between the T332(+) and T332(-) groups of GCB (P = 0.11). Interestingly DLBCL coexpressing survivin and T332 (n = 13) had a significantly worse prognosis (P = 0.009) than the remaining single positive and double negative cases (n = 31). In conclusion, survivin and the novel MAb, T332, might be a good predictor of DLBCL and its subtypes.
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PMID:Expression of survivin and of antigen detected by a novel monoclonal antibody, T332, is associated with outcome of diffuse large B-cell lymphoma and its subtypes. 1594 89

(De-)regulation of apoptosis plays an important role in normal and malignant lymphopoiesis. Apoptosis-regulating genes of the BCL-2 family and the recently identified inhibitors of apoptosis (IAP) family have been implicated in different types of non-Hodgkin lymphoma (NHL). To investigate whether expression of specific apoptosis-regulating genes correlated with different types of lymphoid malignancies, we measured the expression of five BCL-2 family genes, four IAP family genes and SMAC by real-time quantitative polymerase chain reaction in patient samples. In total, 137 samples from B- and T-cell acute lymphoblastic leukaemia (ALL), B-cell chronic lymphocytic leukaemia (CLL), six different NHL types and three control tissue types were analysed. The data were further analysed using cluster and discriminant analysis. Three specific expression patterns were identified for CLL, ALL and NHL respectively. CLL samples, as well as B-ALL and follicular lymphoma samples showed high similarity in the expression of these apoptosis-regulating genes and could be distinguished from each other and other diseases and controls. Discriminant analysis identified three members of the IAP family, C-IAP1, C-IAP2 and SURVIVIN, as the most informative genes to discriminate between these lymphoid malignancies.
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PMID:Expression of C-IAP1, C-IAP2 and SURVIVIN discriminates different types of lymphoid malignancies. 1615 55

In order to investigate the expression change of survivin in non-Hodgkin lymphoma (NHL) and its possible effects on NHL development, the expression of survivin, Ki-67, caspase3 and FVIIIRAg in reactive lymphoid hyperplasia (RH) and NHL was detected by immunohistochemical assay, and apoptosis index (AI) in RH and NHL by TUNEL analysis. The results showed that the expression of survivin is significantly higher in aggressive NHL than in indolent NHL (P<0.01), while there was no statistically significant difference between RH and indolent NHL (P>0.05). The expression of survivin had a significantly positive correlation with the expression of Ki-67 and FVIIIRAg (r=0.6495, 0.6635, respectively, both P<0.01), and a negative correlation with the expression of caspase3 and AI (r=-0.5820, -0.6013, respectively, P<0.01). It was suggested that survivin may contribute to the progression of NHL by playing an important role in promoting cell proliferation, inhibiting cell apoptosis and enlisting angiogenesis. Survivin expression is closely related to malignant grade and therefore may be considered an important prognostic factor of NHL.
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PMID:Expression of survivin in human non-Hodgkin lymphoma and its correlation with proliferation and angiogenesis. 1721 52

Apoptosis-related genes and proteins and proliferation activity and their relationship with Epstein-Barr virus (EBV) is a contemporary issue. In this study, prognostic or pathogenetic roles of EBV latent infection, proliferating activity, and apoptosis-regulating proteins in pediatric Hodgkin lymphomas were explored. EBV-EBER, lmp-1, ki-67, bcl-2, survivin, Bax, fas, c-myc, and p53, and apoptotic index were analyzed in 63 pediatric Hodgkin lymphoma cases. The results were evaluated by chi-square, Mann Whitney U test, Pearson correlation analysis, and Kaplan Meier survival analysis. Thirty-two cases were stage I or II, whereas 31 cases were stage III or IV. The mean age was 8.4 +/- 63.54 years. EBV was positive in 52 (82.5%) cases. Overall survival was 94% and event-free survival 83.6%. Bax expression was observed 74.6%, bcl-2 47.6%, survivin 43%, p53 33.3%, fas 54%, and c-myc 25.4%. The mean apoptotic index was 18.22%. The mean proliferation index was 57.83%. The proliferation index was positively related with EBV but not with prognosis. None of the parameters were related with prognosis. EBV was negatively related with the apoptotic index. There were no relationships between bax, bcl-2, survivin, p53, fas, and c-myc with EBV. These results suggest that EBV might play a role in Hodgkin lymphoma pathogenesis by inducing proliferative activity and inhibiting apoptosis. Apoptosis-related proteins were not correlated with EBV. None of the parameters was found to predict prognosis.
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PMID:Prognostic significance of cell proliferation and apoptosis-regulating proteins in Epstein-Barr virus positive and negative pediatric Hodgkin lymphoma. 1803 36

Although treatment of Hodgkin's lymphoma (HL) with a multi-drug approach has been very successful, its toxicity becomes evident after several years as secondary malignancies and cardiovascular disease. Therefore, the current goal in HL treatment is to find new therapies that specifically target the deregulated signaling cascades, such as NF-kappaB and STAT3, which cause Hodgkin and Reed-Sternberg (H-RS) cell proliferation and resistance of apoptosis. Based on the above information, we investigated the capacity of curcumin to inhibit NF-kappaB and STAT3 in H-RS cells, characterizing the functional consequences. Curcumin is incorporated into H-RS cells and acts inhibiting both NF-kappaB and STAT3 activation, leading to a decreased expression of proteins involved in cell proliferation and apoptosis, e.g. Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1, survivin, c-myc and cyclin D1. Interestingly, curcumin caused cell cycle arrest in G2-M and a significant reduction (80-97%) in H-RS cell viability. Furthermore, curcumin triggered cell death by apoptosis, as evidenced by the activation of caspase-3 and caspase-9, changes in nuclear morphology and phosphatidylserine translocation. The above findings provide a mechanistic rationale for the potential use of curcumin as a therapeutic agent for patients with HL.
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PMID:Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-kappaB and STAT3 pathways in Hodgkin's lymphoma cells. 1838 90


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