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)

Malignant tumors arising from endometriosis are rare. A frequency of about 1% has been reported with in 80% the ovary, and in 20% extragonadal sites being affected. The most common extragonadal manifestations are the rectosigmoid and the rectovaginal septum. For extragonadal malignant tumors arising from endometriosis, complete resection followed by post-operative radiotherapy, possibly plus adjuvant progestin therapy, is the treatment of choice. Endometriosis-associated ovarian carcinomas are likely to present with lower stage disease and predominantly lower grade tumors. While their treatment follows that of common ovarian cancer, a poorer response to chemotherapy must be considered. As unopposed estrogen replacement therapy has been identified as a risk factor for the development of endometriosis-associated cancer, it is not recommended for hormone replacement therapy in women with a history of endometriosis. Loss of heterozygosity and mutations of the PTEN tumor suppressor gene may be early events of tumorigenesis. Endometriosis and its malignant transformation, perhaps, may serve as a suitable model in this regard. According to recent studies, endometriosis is associated with an increased relative risk of non-Hodgkin lymphoma.
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PMID:[Endometriosis and malignoma]. 1450 56

Activation of the Rel/NF-kappaB signal transduction pathway has been associated with a variety of animal and human malignancies. However, among the Rel/NF-kappaB family members, only c-Rel has been consistently shown to be able to malignantly transform cells in culture. In addition, c-rel has been activated by a retroviral promoter insertion in an avian B-cell lymphoma, and amplifications of REL (human c-rel) are frequently seen in Hodgkin's lymphomas and diffuse large B-cell lymphomas, and in some follicular and mediastinal B-cell lymphomas. Phenotypic analysis of c-rel knockout mice demonstrates that c-Rel has a normal role in B-cell proliferation and survival; moreover, c-Rel nuclear activity is required for B-cell development. Few mammalian model systems are available to study the role of c-Rel in oncogenesis, and it is still not clear what features of c-Rel endow it with its unique oncogenic activity among the Rel/NF-kappaB family. In any event, REL may provide an appropriate therapeutic target for certain human lymphoid cell malignancies.
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PMID:The c-Rel transcription factor and B-cell proliferation: a deal with the devil. 1475 44

We propose that there are two main classes of Epstein-Barr virus (EBV) associated lymphomas: primarily malignant Burkitt's Lymphoma (BL) and Hodgkin's Disease (HD), on one hand, and primarily benign lymphoproliferations, e.g., post-transplant lymphoproliferative disease (PTLD) on the other hand. PTLD may start as a benign lymphoproliferation which becomes malignant if out of T cell control for too long. Our discovery of a binding site for the oncoprotein c-Myc at a central position of the EBV genome favours a distinction of pathogenetic pathways or scenarios for the proposed lymphoma classes. In the first scenario nuclear maintenance of the EBV genome and activation of viral anti-apoptotic functions with the help of c-Myc are indispensable for the origin of malignant tumours (BL, HD) from the germinal centre B-cell. In the second scenario expression of the main viral transforming protein EBNA2 is essential for immortalisation and non-malignant morphological transformation of any (germinal centre derived or non-germinal centre) B-cell in the absence of T cell control. Although EBNA2 expression is permissible, under specific circumstances, in malignant B-cells, it is not required for oncogenesis.
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PMID:EBV-associated neoplasms: alternative pathogenetic pathways. 1497 9

One of the most difficult challenges of oncology is to improve methods for early tumor detection, which is crucial for the success of cancer therapy and greatly improves the survival rate. Underglycosylated mucin-1 antigen (uMUC-1) is one of the early hallmarks of tumorigenesis and is overexpressed and underglycosylated on almost all human epithelial cell adenocarcinomas as well as in nonepithelial cancer cell lines, as well as in hematological malignancies such as multiple myeloma, and some B-cell non-Hodgkin lymphomas. In this study, we designed, synthesized, and tested a novel multimodal imaging probe specifically recognizing in vivo uMUC-1 antigen in an animal model of human cancer. Furthermore, in vivo magnetic resonance- and near-infrared-imaging experiments on tumor-bearing animals showed specific accumulation of the probe in uMUC-1-positive tumors and virtually no signal in control tumors. We expect that this probe has a potential to greatly aid in screening prospective patients for early cancer detection and in monitoring the efficacy of drug therapy.
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PMID:In vivo targeting of underglycosylated MUC-1 tumor antigen using a multimodal imaging probe. 1499 45

Lymphoid tumours comprise the acute and chronic leukaemias, the broad spectrum of lymphomas, including Hodgkin's disease, and multiple myeloma. The subdivision of the acute leukaemias according to the proliferating type of white blood cells has had a major impact on the care of these patients. More recently, specific chromosomal translocations have been used to identify patients who may benefit from more intensive therapies. The novel high-throughput genomic technologies, such as microarrays, provide new avenues for the molecular diagnosis of the haematological malignancies. Rapid advances in genome sequencing and gene expression profiling provide unprecedented opportunities to identify specific genes involved in complex biological processes, including tumorigenesis. The features of microarray technology and the variety of experimental approaches to elucidate lymphoid malignancies are discussed. Microarray technology has the potential to lead to more accurate prognostic assessment for patients and is expected to ultimately allow the clinician to select therapies optimally suited to each patient.
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PMID:Gene expression signatures in lymphoid tumours. 1506 68

Primary effusion lymphomas (PELs) represent a unique non-Hodgkin lymphoma that is consistently infected by Kaposi sarcoma herpesvirus (KSHV). PEL cells express high levels of the cell cycle inhibitor p27(KIP1) and yet proliferate actively. KSHV genome encodes a viral cyclin homolog, v-cyclin, which has previously been implicated in down-regulation of p27(KIP1) levels. To address how PEL cells can tolerate high p27(KIP1) levels, we investigated functional interactions between v-cyclin and p27(KIP1) using PEL-derived cell lines as a model system. Here we demonstrate that v-cyclin and p27(KIP1) stably associate in PEL cells in vivo suggesting an attractive model by which p27(KIP1) is inactivated in the actively proliferating PEL cells. Moreover, we show that v-cyclin and cyclin-dependent kinase 6 (CDK6) form an active kinase without p27(KIP1) and that CDK6 is the in vivo catalytic subunit of v-cyclin in PEL cells. These findings suggest that KSHV may promote oncogenesis in PEL by expressing v-cyclin, which both overrides negative cell cycle controls present in the PEL precursor cells and induces a strong proliferative signal via CDK6 kinase activity.
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PMID:KSHV viral cyclin binds to p27KIP1 in primary effusion lymphomas. 1527 92

T-bet, a T-box transcription factor, is expressed in CD4+ T lymphocytes committed to Th1 T-cell development and in a subset of T-cell non-Hodgkin lymphomas. Recent evidence indicates that T-bet also is expressed in B lymphocytes and might participate in immunoglobulin class switching. We examined T-bet expression in 116 cases of B-cell lymphoproliferative disorders by immunostaining and found that T-bet was expressed consistently in precursor B-cell lymphoblastic leukemia/lymphoblastic lymphoma (14/14 cases) in contrast with precursor T-cell lymphoblastic leukemia/lymphoblastic lymphoma, which is consistently T-bet- (13 cases), as previously reported. T-bet is expressed in memory B cell-derived neoplasms (chronic lymphocytic leukemia, marginal zone lymphoma, hairy cell leukemia; 35/42 cases) but not in cases of mantle cell, follicular, and large cell lymphoma (43 cases). Expression of T-bet in precursor B-cell lymphoblastic leukemia/lymphoblastic lymphoma was confirmed by Western blot analysis. The expression of T-bet in a significant subset of B-cell lymphoproliferative disorders but not in the vast majority of reactive B cells suggests it might have a role in the oncogenesis of T-bet+ B-cell neoplasms. In addition, T-bet should serve as a useful new marker for the diagnosis and subtyping of B-cell lymphoproliferative disorders.
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PMID:T-bet, a T-cell-associated transcription factor, is expressed in a subset of B-cell lymphoproliferative disorders. 1532 32

To assess the distribution of lymphomas in Taiwan according to the WHO (World Health Organization) classification, 175 recently diagnosed cases of malignant lymphomas were studied and the clinicopathologic data were analyzed. B-cell lymphomas accounted for 57.1% of cases, T-cell lymphomas 38.9%, and Hodgkin's lymphoma 4%. Extranodal lymphomas predominated (55.4%). The most common subtype of B-cell lymphoma was diffuse large B-cell lymphoma (33.1%). All tumor types believed to be derived from germinal center (GC) B-cells including follicular lymphoma (4.6%), Burkitt lymphoma (1.7%), Hodgkin lymphoma (4.0%), and GC-like diffuse large B-cell lymphoma (as defined by combined expression of bc1-6 and CD10) were rather uncommon as compared to frequencies seen in series from Western countries. The common T-cell lymphomas included nasal and extranasal NK/T cell lymphoma (7.4%), mycosis fungoides (7.4%), and unspecified peripheral T-cell lymphoma (6.9%). Adult T-cell leukemia/lymphoma was very uncommon and accounts for only 0.6%. The proportional increase in T-cell lymphomas that were unrelated to type I human T-cell lymphotropic virus (HTLV-1) may be linked to differential Epstein-Barr virus (EBV) oncogenesis. The survival data revealed that mantle cell lymphoma, NK/T-cell lymphoma, unspecified peripheral T-cell lymphoma, and subcutaneous panniculitis-like T-cell lymphoma had an aggressive course. Our results confirm the utility of the WHO classification scheme for prognostic stratification and further highlight the distinctive distribution pattern of malignant lymphoma in Taiwan including the higher relative incidence of T cell lymphomas and the rarity of germinal center-derived B-cell tumors.
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PMID:Distribution and prognosis of WHO lymphoma subtypes in Taiwan reveals a low incidence of germinal-center derived tumors. 1535 36

Splenic marginal zone lymphoma (SMZL) is a lymphoma type of putative marginal zone B-cell origin. No specific genetic alterations have yet been demonstrated in SMZL. Clinically, SMZL is a low-grade B-cell non-Hodgkin lymphoma. However, the presence of p53 mutation, 7q22-7q32 deletion or the absence of somatic hypermutations of immunoglobulin genes has been correlated with a worse prognosis. In this study, we analyzed genome-wide gene expression of 24 cases of SMZL using the microarray technique. The AP-1 transcription factors c-jun, junD, junB, and c-fos as well as Notch2 were found to be specifically up-regulated. These data were confirmed by real-time PCR and immunohistochemical staining of tissue sections. The absence of concordant high expression of the MAP kinases, the signaling cascade leading to AP-1 up-regulation, suggests autoregulation of the AP-1 transcription factors and an important role in SMZL oncogenesis. High expression of Notch2, a transcription factor that induces marginal zone B-cell differentiation, is highly suggestive for a marginal zone B-cell origin of SMZL. In addition, SMZL with the 7q deletion showed high expression of TGF-beta1 and low expression of the DNA helicase XPB, a crucial part of the nucleotide excision repair complex, possibly explaining the more aggressive clinical course of those cases.
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PMID:Constitutive expression of the AP-1 transcription factors c-jun, junD, junB, and c-fos and the marginal zone B-cell transcription factor Notch2 in splenic marginal zone lymphoma. 1550 68

Hodgkin's lymphoma is a unique neoplasm of B lymphocytes. Recent data provide new understandings of the pathogenesis and options for staging and therapy of the disease. Three specific topics are addressed in this chapter. In Section I, Dr. Richard Ambinder reviews implications of the relationship of Epstein-Barr virus (EBV) and Hodgkin's lymphoma. This relation includes varying geographic epidemiologic associations, including varying associations with the clinical syndrome of infectious mononucleosis. There are plausible mechanisms, including processes initiated by viral proteins, by which EBV might lead to tumorigenesis. These mechanisms include promotion of genetic instability and alteration of normal processes of apoptosis. In addition to an epidemiologic association and potential role in pathogenesis, viral antigens may pose theoretical targets for anti-cancer therapies, including vaccination. In Section II, Dr. Sigrid Stroobants describes the potential role of positron emission tomographic (PET) scanning. By assessing differences in the metabolic activities of cancer cells, PET scanning may be superior to computerized tomographic scanning, which is limited to showing structural anatomical abnormalities. In patients with Hodgkin's and non-Hodgkin's lymphoma, PET scanning has been tested as an initial staging tool, to assess the rate of therapeutic response from a prognostic perspective, and to differentiate residual tumor from fibrotic masses in patients who have completed therapy. Particularly in assessing the nature of a residual mass seen with other post-therapeutic imaging modalities, PET scanning may provide unique information; very high negative predictive values have been reported. However, before this technology can be recommended for incorporation into standard management, properly conducted prospective trials are required to better evaluate the clinical utility of PET with respect to eventual patient outcomes. In Section III, Dr. Ralph Meyer reviews current data regarding the management of patients with limited-stage Hodgkin's lymphoma. Over the past decade, standard treatment has evolved to consist of combined-modality therapy that includes an abbreviated course of chemotherapy and involved-field radiation. As this therapy continues to include radiation therapy, patients will remain at risk of long-term toxicities that include the development of second cancers and cardiovascular events. These "late-effects" now account for more deaths than those attributed to progressive Hodgkin's lymphoma. Comparative data testing the role of chemotherapy alone are now available and demonstrate that omission of radiation therapy results in small but statistically significant reduction in disease control, but no detectable differences in overall survival. Further follow-up will clarify whether chemotherapy alone is the preferred treatment option; at present patients should be informed of the trade-offs involved in choosing between this option and combined modality therapy.
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PMID:Hodgkin's lymphoma: evolving concepts with implications for practice. 1556 83


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