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

There are two ways of connecting Epstein-Barr virus (EBV) with the uncontrolled growth of EBV infected B lymphocytes: in case of evident immunosuppression when the control by cellular immunity is missing or in the case of pathological growth of malignant clone as a result of genetic translocations. Today, EBV is linked with the development of lymphomas in immunosuppressed patients, Hodgkin's and Burkitt's lymphoma and nasopharyngeal carcinoma. The presence of EBV genome in these patients can be confirmed in malignant cells, in lower or higher percent, as well as the high titers of antibodies against specific virus antigens. Hepatitis B viral infection (HBVI) of specific chronic course and associated with intensified inflammation and mitotic activity is of one of the most important factors in the appearance of hepatocellular carcinoma. Although the integration of viral DNA in DNA of hepatocytes has been one of the possible preconditions for carcinogenesis, recently a great attention has been paid to the inactivation of p53 suppressor gene, being a transcriptive transactivator. Other possible cofactors of carcinogenesis imply long-lasting viral replication, coinfection with HVB, HCV or HDV, interaction with other chemical carcinogens (hormones, aflatoxin, alcohol and similar). In distinction from other human DNA viruses, Hepatitis C virus (HCV) is a RNA virus which is not integrated in genome of hepatocyte and active replication of virus is maintained even when hepatocellular carcinoma is detected. It has been assumed that HCV inactivate or mutate the gene of tumor suppression p53 in an early stage of hepatocellular carcinoma development.
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PMID:[Epstein-Barr, hepatitis B and hepatitis C virus infections and their oncogenic potentials]. 947 11

Telomerase is a key enzyme in carcinogenesis; telomerase activity has been found in more than 90% of human tumors. Understanding the regulation of this enzyme will improve our knowledge of tumor biology and may lead to novel strategies in cancer therapy. We examined effects of growth arrest on telomerase activity in the human immortalized cell lines U 937 (lymphoma) and L 428 (Hodgkin's disease). Cells were starved by serum depletion for 4 days. After readdition of serum, a recovery phase followed. Cell proliferation was monitored with the monoclonal antibody Ki-S5. In the absence of serum, telomerase levels declined fivefold. After serum readdition, recovery to threefold increased level was observed. Furthermore, the prevalence of telomerase-positive cells in normal tissues is an important issue for understanding tumorigenesis. Our TRAP assay is robust against false positives and in mixed cell samples, we found a rather limited sensitivity of the telomere repeat amplification protocol (TRAP) assay. This means that adequate screenings for telomerase-positive somatic cells have to include enrichment steps.
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PMID:Regulation of telomerase activity in quiescent immortalized human cells. 980 18

The two gene products of the CDKN2A gene, p16 and p19ARF, have recently been linked to each of two major tumour suppressor pathways in human carcinogenesis, the RB1 pathway and the p53 pathway. p16 inhibits the phosphorylation of the retinoblastoma gene product by cyclin D-dependent kinases, whereas p19ARF targets MDM2, a p53 inhibitory protein, for degradation. A deletion of CDKN2A would therefore disturb both pathways. To explore the p53 pathway genes as a functional unit in diffuse large B cell non-Hodgkin's lymphomas (DLCL), we wanted to see whether there exists mutually exclusiveness of aberrations of CDKN2A, MDM2 and p53, since this has not been analysed previously. We investigated 37 DLCL for aberrations of p15, p16, p19ARF, MDM2, and p53 at the epigenetic, genetic and/or protein levels. Homozygous deletion of CDKN2A was detected in seven (19%) of 37 tumours, and another three cases were hypermethylated at the 5' CpG island of p16. No point mutations were found in CDKN2B or CDKN2A. Immunohistochemical staining of formalin-fixed, paraffin-embedded tissue for p16 confirmed these results, as all tumours with alterations of CDKN2A were p16 immunonegative. We found p53 mutations in eight (22%) cases and MDM2 overexpression in 16 (43%) tumours. Twenty-three (62%) tumours had alterations of one or more p53 pathway components (p53, p19ARF and MDM2). Furthermore, 7/9 (78%) p16-immunonegative tumours showed co-aberration of p53 and/or MDM2. The lack of correlation between these aberrations suggests that DLCL acquire additional growth advantage by inactivating both of these critical regulatory pathways.
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PMID:Aberrations of the p53 pathway components p53, MDM2 and CDKN2A appear independent in diffuse large B cell lymphoma. 1008 36

Epstein-Barr virus (EBV) was first reported as the causative virus of Burkitt's lymphoma in 1964. Since then, EBV has also been associated with infectious mononucleosis, AIDS and transplant-related B cell lymphomas, and nasopharyngeal cancer. The virus has further been linked with T cell lymphomas, Hodgkin disease, and NK leukemia or LGL leukemia, establishing a concept of a wide spectrum of EBV associated malignant disorders. EBV DNA encodes several proteins such as EBNA1-6, LMP 1, 2 and others. Recent studies have demonstrated that EBNA2, EBNA5, EBNA3A, EBNA 3C are essential for transformation, and that any gene product is not sufficient to transform cells by itself. Further there are different mechanisms of virus-associated transformation or carcinogenesis among EBV-associated malignant disorders. On the other hand, human T lymphotropic virus type I (HTLV-I) is known as a causative virus of adult T cell leukemia (ATL). However, precise molecular mechanisms of leukemogenesis in ATL still remains unclear. Some additional factors to HTLV-I infection are supposed to be involved in complete leukemogenesis. We demonstrated that HTLV-I infected T cells and primary ATL cells express EBV receptor/CD21 on the cell surface. Therefore, it is possible that EBV infection is one of the factors. We further investigated this possibility in 6 HTLV-I infected T cell lines and primary ATL cells from 18 patients with ATL. However, no EBV genome was detected in both T cell lines and primary ATL cells. EBV involved T-cell lymphoma has unique clinical manifestations as compared to non-EBV involved T-cell lymphoma. Therefore, it is still possible that a small group of ATL patients with unique clinical manifestations is associated with EBV.
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PMID:Epstein-Barr virus involvement in T-cell malignancy: significance in adult T-cell leukemia. 1034 73

Xenobiotic-metabolizing enzymes constitute an important line of defence against a variety of carcinogens. Many are polymorphic, constituting the basis for the wide inter-individual variation in metabolic capacity and possibly a source of variation in the susceptibility to chemical-induced carcinogenesis. The aim of this study was to determine the existence of any association between the main genetic polymorphisms of cytochrome P450 2D6 (CYP2D6), glutathione S-transferase M1 (GSTM1) and N-acetyltransferase 2 (NAT2) and an altered risk for haematological neoplasias. A total of 160 patients and 128 controls were genotyped by means of PCR-RFLP-based assays. Mutated alleles comprising CYP2D6*4, GSTM1*0, NAT2*5A, *5B, *5C, *6 and *7 were analysed along with the wild-type alleles. The results showed a higher frequency of CYP2D6 extensive metabolizers carrying two functional alleles in the leukaemia group, when compared with controls (76.6 versus 57.0%, P = 0.008). No differences were found in the case of Hodgkin and non-Hodgkin lymphomas. Analysis of the GSTM1 and NAT2 polymorphisms failed to show an association with any of the neoplasias, although a near significant increase in fast acetylators was also found in the leukaemia group (50.0 versus 35.9%, P = 0.06). The results suggest an association of extensive metabolism with an increased risk for leukaemia, possibly by an increase in the metabolic activation of chemical carcinogens or linkage to another cancer-causing gene. Opposite findings presented in other studies may reflect geographical differences in the type of environmental carcinogens to which different populations are exposed.
Carcinogenesis 1999 Jul
PMID:Genetic polymorphism of CYP2D6, GSTM1 and NAT2 and susceptibility to haematological neoplasias. 1038 93

Today the majority of children and adolescents diagnosed with Hodgkin's lymphoma will enjoy long-term disease-free survival. As a result, contemporary treatment strategies have focused on reducing therapy for patients with favorable disease presentations and reserved aggressive treatment modalities for patients with relapsed or refractory disease. The desire to avoid late treatment toxicity has prompted refinements in therapy designed to reduce growth impairment, second malignancy, and life-threatening organ dysfunction in long-term survivors. Treatment with radiation therapy alone is recommended only for older patients with localized disease who have achieved skeletal maturity, but requires surgical staging and places greater volumes of normal tissues at risk for late carcinogenesis. Treatment with chemotherapy alone avoids the long-term growth, organ dysfunction, and solid tumor induction associated with high-dose, extended-field radiation. However, these protocols prescribe higher cumulative doses of alkylating agent chemotherapy, which may increase the risk of treatment complications from myelosuppression, gonadal injury, and secondary leukemia. Combined modality therapy regimens have resulted in excellent treatment outcomes and reduced the incidence of treatment sequelae by utilizing lower doses and smaller volumes of radiation therapy and fewer cycles of less toxic chemotherapy in clinically staged children. Risk-adapted therapies using two to four cycles of multiagent chemotherapy and lower radiation doses and volumes have maintained excellent disease-free survival rates in clinically staged patients with localized favorable disease presentations. Novel approaches including compacted dose-intensive multiagent chemotherapy are currently under investigation with the objectives of improving outcome and reducing treatment sequelae in patients with advanced and unfavorable disease.
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PMID:Treatment of pediatric Hodgkin's lymphoma. 1046 31

Specific defects in DNA repair pathways are reflected by DNA microsatellite instability (MSI) and play an important role in carcinogenesis. Reported frequencies in gastric non-Hodgkin's lymphomas (NHL) vary from 14% to as high as 90%. Another form of genetic instability in tumours is allelic imbalance (AI) due to loss or gain of genetic material at a specific chromosomal region. This might point to the presence of a tumour suppressor gene or oncogene. We examined both MSI and AI in 26 gastric lymphomas (10 low-grade and 13 high-grade MALT lymphomas and three cases lacking MALT features and categorised as diffuse large B cell lymphoma (DLCL)). Tumour components and normal cells (epithelium, muscle) were microdissected from paraffin-embedded resection samples. Contrary to other studies we did not observe frequent MSI when investigating 18 different loci distributed over 12 chromosomes. Microsatellite instability of a single locus was found in 1/10 (10%) low-grade MALT lymphomas and 2/13 (15%) high-grade MALT lymphomas. These data indicate that DNA mismatch repair genes do not play a role in the pathogenesis of these lymphomas. Allelic imbalance was detected in 60% (6/10) of low-grade MALT lymphomas, in 62% (8/13) of high-grade MALT lymphoma and in 67% (2/3) of DLCL. In high-grade lymphomas more loci showed AI (one to seven loci, with a mean of 2.5 loci per case) than in the low-grade lymphomas (one to two loci, with a mean of 1.3 loci per case), possibly reflecting an increased genomic instability.
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PMID:Frequent allelic imbalance but infrequent microsatellite instability in gastric lymphoma. 1055 55

Over the past few decades, there has been a tremendous increase in cancer biology data and treatment. Cancer research has opened exciting new areas of cellular and molecular biology. Month by month, new genes which regulate the carcinogenesis process are being discovered. The result is an incredible knowledge of cancer: what makes a cancer cell a cancer cell, what cancer cells need to develop, and how cancer cells behave, interact, overgrow and die. In parallel, gene manipulation within cells lets us foresee future possibilities of new cancer treatments. On the other hand, this combination of increased knowledge and powerful new techniques has provided no effective cancer therapy. As it has been quoted during the <Update and Intensive Review of Internal Medicine> meeting held in New York, August 1999: <. The success in treating Hodgkin's disease means that patients now live enough to develop complications related to the treatment>. Thus, after dedicated decades of excellent research, cancer remains a significant human, clinical, and economical burden. The purpose of this review is 2-fold. First, to analyze areas of basic cancer research that still await adequate scientific explanations. Second, to stress that, for its continuing advancement, cancer research is dependent upon close relationships among many disciplines; an intimate alignment of oncologists with biochemists, geneticists, immunologists, experimental pathologists, and pharmacologists is needed. In light of the great success registered at the basic science level but lack of effective therapies, it would be wise to establish human and economical resources addressed to a multidisciplinary collaborative effort in cancer research.
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PMID:A critical perspective in cancer research (Review). 1056 30

Epstein-Barr virus (EBV), a ubiquitous B-lymphotrophic herpesvirus, has been found in the tumor cells of a heterogeneous group of malignancies (Burkitt's lymphoma, lymphomas associated with immunosuppression, other non-Hodgkin's lymphomas, Hodgkin's disease, nasopharyngeal carcinoma, gastric adenocarcinoma, lymphoepithelioma-like carcinomas, and immunodeficiency-related leiomyosarcoma). As the epidemiologic characteristics of these cancers have not been considered together, this review seeks to relate their incidence patterns and risk factors to EBV biology and virus-host interaction in an attempt to help elucidate factors involved in EBV-related carcinogenesis. We include a brief review of EBV virology and primary infection to provide a biologic context for considering the epidemiology, summarize the most salient epidemiologic features of each malignancy, synthesize epidemiologic data by risk factor to uncover commonalities and informative contrasts across the diseases, and propose hypotheses regarding etiologic mechanisms, based on the possible effect of the risk factors at various stages in the viral life cycle.
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PMID:Epstein-barr virus-associated malignancies: epidemiologic patterns and etiologic implications. 1078 47

Radiation is commonly used to treat early-stage Hodgkin's disease. As the risk of recurrent Hodgkin's disease decreases as time from treatment elapses, the risk of radiation-induced breast cancer rises. Women irradiated between the time of puberty and the age of 30 are at the highest risk. The median time to breast cancer following radiation in this age group is approximately 15 years, usually when women are aged between 30 and 40, and often before regular breast screening is implemented. Risk factors associated with breast cancer development include age at irradiation, time since treatment and the radiation dose received. Current screening for breast cancer after Hodgkin's disease is inconsistent. In this article we review breast development, mechanisms of radiation-induced carcinogenesis, and findings from retrospective studies on Hodgkin's disease and breast cancer. We also review future considerations of management, including assessment of risk awareness in these women, guidelines for follow-up and screening, and chemoprevention both during and after treatment of Hodgkin's disease. The literature reviewed was obtained from Medline using the key words: breast cancer, Hodgkin's disease and radiation-induced cancer. The search was limited to English language literature. Other sources include reference lists in books and published papers.
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PMID:Breast cancer risk following irradiation for Hodgkin's disease. 1091 84


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