UMLS:C0019829 - FACTA Search

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Query: UMLS:C0019829 (Hodgkin's disease)
30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detection of novel DNA sequences in Kaposi's sarcoma (KS) and AIDS-related body cavity-based, non-Hodgkin's lymphomas suggests that these neoplasms are caused by a previously unidentified human herpesvirus. We have characterized this agent using a continuously infected B-lymphocyte cell line derived from an AIDS-related lymphoma and a genomic library made from a KS lesion. In this cell line, the agent has a large episomal genome with an electrophoretic mobility similar to that of 270-kb linear DNA markers during clamped homogeneous electric field gel electrophoresis. A 20.7-kb region of the genome has been completely sequenced, and within this region, 17 partial and complete open reading frames are present; all except one have sequence and positional homology to known gammaherpesvirus genes, including the major capsid protein and thymidine kinase genes. Phylogenetic analyses using both single genes and combined gene sets demonstrated that the agent is a gamma-2 herpesvirus (genus Rhadinovirus) and is the first member of this genus known to infect humans. Evidence for transient viral transmission from infected to uninfected cells is presented, but replication-competent virions have not been identified in infected cell lines. Sera from patients with KS have specific antibodies directed against antigens of infected cell lines, and these antibodies are generally absent in sera from patients with AIDS without KS. These studies define the agent as a new human herpesvirus provisionally assigned the descriptive name KS-associated herpesvirus; its formal designation is likely to be human herpesvirus 8.
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PMID:Primary characterization of a herpesvirus agent associated with Kaposi's sarcomae. 852 68

The serum levels of soluble ICAM-1 (sICAM-1, sCD54) were significantly elevated (p = .0006) in patients with Hodgkin's disease (HD) (n = 101) compared to healthy controls (n = 31). Serum levels of sICAM-1 in HD correlated significantly with the presence of B-symptoms, histology and tumour burden as reflected in the Ann Arbor staging system, but not to bulky disease. sICAM-1 was compared to other serum factors claimed to be of prognostic significance in HD, including erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), deoxythymidine kinase (TK), soluble interleukin-2 receptor (sIL-2R, sCD25) and soluble CD30 (sCD30, sKi-1-antigen). Serum levels of sICAM-1 correlated positively with all of these markers. In univariate regression analyses, all but ESR correlated with disease-free survival but only sICAM-1, sIL-2R and sCD30 correlated with overall survival. In multivariate analyses only sIL-2R (as a continuous variable) added independent prognostic information in addition to age, stage and B-symptoms. sICAM-1 and sCD30 approached significance (p = 0.07 and p = 0.08, respectively) for disease-free survival. sCD30 correlated with overall survival (p = 0.03) while sICAM-1 did not. When dichotomised at optimal cut-off levels, sICAM-1 as well as sIL-2R and sCD30 added independent prognostic information for both disease-free and overall survival. Based on the present observations, it appears that sICAM-1 may be a predictor for relapse and survival in HD. Determination of serum levels of sICAM-1 (in addition to sIL-2R and sCD30) may thus be of potential value when selecting HD patients eligible for intensive therapy in clinical trials.
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PMID:Soluble ICAM-1 in Hodgkin's disease: a promising independent predictive marker for survival. 853 15

The serum levels of soluble ICAM-1 (CD54) were significantly elevated in patients with non-Hodgkin's lymphomas (NHL, n=127) and hairy cell leukaemia (HCL, n=15) compared with healthy controls (n=31). In high-grade malignant NHL (n=79) the sICAM-1 levels correlated with the tumour mass as reflected in the Ann Arbor staging system but not with bulky disease. Further, the sICAM-1 levels correlated with disease activity as reflected by the presence of B symptoms and with other known prognostic markers. In particular serum thymidine kinase (sTK). In patients with low-grade malignant NHL (n=48) a trend towards higher serum levels of sICAM-1 was found in patients with advanced stage and B symptoms. In both low and high-grade malignant NHL, elevated levels of sICAM-1 were associated with poorer overall and disease-free survival. The present results indicated that sICAM-1 levels have a prognostic power equal to that of other serum markers claimed to be of prognostic value in NHL, namely serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), beta-2-microglobulin (beta2m), serum thymidine kinase (sTK), albumin and orosomucoid. The cellular origin and the possible interactions between soluble and surface ICAM-1 and its ligands needs further exploration.
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PMID:Elevated serum levels of soluble ICAM-1 in non-Hodgkin's lymphomas correlate with tumour burden, disease activity and other prognostic markers. 879 Jan 63

In this work we have explored the use of adenoviral vectors for the purging of cancer cells from hematopoietic stem cell (HSC) autografts. We showed that a recombinant adenovirus expressing the herpes simplex-1 thymidine kinase gene (AD-tk) plus ganciclovir (GCV) killed HELA cells more effectively than did GCV alone. HELA cells were then mixed with human HSCs and exposed to AD-tk/GCV. AD-tk/GCV reduced the number of HELA colonies to 4% of control values, with no detectable reduction in the hematopoietic progenitor, colony forming unit-granulocyte/monocyte (CFU-GM). Similar studies of the JB6 non-Hodgkins lymphoma cell line showed a reduction to 5% of controls; studies of MCF-7, a breast carcinoma cell line, showed a reduction to 30% of controls, with no CFU-GM toxicity. Thus, AD-tk mediated selective killing of contaminating tumor cells. We also evaluated a recombinant adenovirus encoding the tumor suppressor gene p53 (AD-p53). AD-p53 was able to selectively kill all three cell lines (reducing tumor colonies approximately 100-fold) without any toxicity to CFU-GM. Although both AD-tk/GCV and AD-p53 were effective in these experiments, AD-p53 seemed to be more potent. Adenoviral vectors show promise for selectively targeting cancer cells that contaminate HSC autografts.
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PMID:Selective elimination (purging) of contaminating malignant cells from hematopoietic stem cell autografts using recombinant adenovirus. 885 51

Conventional approaches to the treatment of malignancy are often not curative or are associated with serious complications. New approaches to treatment are needed. A variety of specific approaches to the destruction of virus-associated tumor cells are illustrated in the context of EBV-associated Hodgkin's disease and nasopharyngeal carcinoma. Viral antigens expressed by tumors may be targeted by cytotoxic T cells. Other viral antigens not naturally expressed by tumors may be induced by pharmacologic manipulations such as treatment with demethylating agents. Viral enzymes not naturally expressed by tumors such as thymidine kinase may be induced by protein kinase C activators, thus rendering tumor cells sensitive to killing by ganciclovir.
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PMID:Epstein-Barr virus as a therapeutic target in Hodgkin's disease and nasopharyngeal carcinoma. 894 6

S-TK (Serum thymidine kinase) levels were determined by means of a radioenzyme assay (REA). In 95% of healthy controls (n = 97), S-TK values were below 8.5 U/L. In patients with monoclonal gammopathies of undetermined significance (MGUS) (n = 27) or polyclonal gammopathies (n = 45) the cut off was 10.3 U/L respectively 25 U/L. Patients with viral disease (n = 16), especially infections with Epstein-Barr virus, Hepatitis-virus and HIV, had elevated S-TK values of up to 215 U/L. In 95 patients with multiple myeloma (MM) and 103 patients with other various non-Hodgkin lymphomas (NHL) S-TK levels were investigated. With regard to monoclonal gammopathies, MGUS had lower S-TK than MM patients (p < 0.05) and patients with stage I MM according to Durie and Salmon had S-TK levels significantly lower than those with more advanced stages (p < 0.01). There was a correlation between S-TK and plasma cell labeling index (r = 0.56, p < 0.001). Patients with chronic lymphocytic leukemia showed significantly higher S-TK levels in the RAI stages 3 and 4 than in stages 1 and 2 (p < 0.01). In cases of other malignant NHL in progression sensitivities of S-TK were found to be: immunocytoma 36%, centrocytic/centroblastic-centrocytic lymphoma 54% and high-grade NHL 40% (cut off defined on lymphomas in remission). S-TK levels varied in MM according to the course of disease and response to therapy decreasing at remission and increasing again at relapse. Analogous variations were found in the other NHL. After two years, 83% of patients with a pretreatment S-TK of < 10 U/L and 47% of the patients with a S-TK of > or = 10 U/L were still alive. S-TK proved to be a highly significant prognostic indicator for MM patients (log-rank and Wilcoxon: p < 0.0001). In the other NHL patients with a S-TK level greater than 10 U/L had a median follow-up of only 7 months. NHL patients with lower S-TK levels did not yet reach the median survival time (log-rank and Wilcoxon. p < 0.005). Our results suggest that the determination of S-TK may help to monitor the clinical course of NHL during therapy and predict the prognosis of NHL.
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PMID:Serum thymidine kinase in non-Hodgkin lymphomas with special regard to multiple myeloma. 932 92

Lymphoproliferative disorders associated with Epstein-Barr virus (EBV) infections can occur in the setting of immunosuppression. In some patients, the lymphoproliferative disorder can resemble an aggressive monoclonal non-Hodgkins lymphoma (NHL). These NHL are poorly responsive to conventional therapy. Similarly, antiviral therapy with synthetic nucleosides such as ganciclovir are ineffective because the genes that render the virus susceptible to therapy are not expressed in EBV+ lymphomas. Using a cell line derived from a lung transplant recipient with an EBV+ immunoblastic NHL, we studied the ability of arginine butyrate to induce the expression of EBV thymidine kinase. Arginine butyrate was not only effective in inducing EBV thymidine kinase transcription, but also acted synergistically with the antiviral agent ganciclovir to inhibit cell proliferation and decrease cell viability. Based on these findings, the patient from whom the cell line was derived was treated with arginine butyrate/ganciclovir as well as conventional cytotoxic chemotherapy. No additional toxicity was observed with the arginine butyrate/ganciclovir therapy. Histologic examination of the tumor showed substantial necrosis. These observations suggest the feasibility of arginine butyrate induction of ganciclovir susceptibility in patients with EBV-associated lymphomas.
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PMID:Arginine butyrate-induced susceptibility to ganciclovir in an Epstein-Barr-virus-associated lymphoma. 962 48

We have hypothesized that adenoviral vectors might mediate gene transfer into cell lines derived from human lymphocytic malignancies, such as lymphoma, lymphocytic leukemia, and myeloma. A panel of 33 cell lines was studied for their ability to be transduced by an adenoviral (AD) vector encoding the Escherichia coli beta-galactosidase gene (AD-betagal). A cytochemical assay and a flow cytometry assay both demonstrated that a subset of lymphocytic cell lines can be efficiently transduced by adenoviral vectors. In particular, three of three anaplastic large cell lymphoma lines, two of two Hodgkin's disease cell lines, two of seven Burkitt's lymphoma cell lines, and three of five myeloma cell lines exhibited efficient gene transfer. The ability of an AD vector expressing the thymidine kinase (tk) gene from herpes simplex virus-1 (AD-tk) followed by ganciclovir (GCV) to kill 11 of these lymphocytic cell lines was studied. In eight of the cell lines tested, more than 68% of the cells were killed by AD-tk/GCV. Similar results were obtained using an adenoviral vector expressing the wild-type p53 tumor suppressor gene (AD-p53). Thus, AD-tk/GCV and AD-p53 both demonstrated efficient killing of these cell lines. These data document that adenoviral vectors are valuable reagents for the introduction of genes into selected lymphocytic cell lines. These data also suggest that adenoviral vectors might be useful for gene therapy of subsets of lymphocytic malignancy.
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PMID:Adenoviral vectors efficiently target cell lines derived from selected lymphocytic malignancies, including anaplastic large cell lymphoma and Hodgkin's disease. 981 92

Lymphoproliferative disorders associated with the Epstein-Barr virus (EBV) include non-Hodgkin's lymphoma, Hodgkin's lymphoma, and "post-transplant lymphoproliferative disorders" (PTLD), which occur with immunosuppression after marrow and organ transplantation. PTLD is characterized by actively proliferating, latently infected EBV(+) B-lymphocytes, and often manifests a rapidly progressive fatal clinical course if the immunosuppression cannot be reversed. Lung transplant recipients are a subset of patients at special risk for developing PTLD. The incidence of PTLD development in these patients has been estimated at 5--10%. Whereas immunologic and antiviral therapy have been moderately effective for treating EBV-associated infections in the lytic phase, they have been less useful in the more common latent phase of the disease. One common treatment for herpesvirus infections has targeted the virus-specific enzyme thymidine kinase (TK). The lack of viral TK expression in EBV(+) tumor cells, due to viral latency, makes anti-viral therapy alone ineffective as an anti-neoplastic therapy, however. We have developed a strategy for the treatment of EBV-associated lymphomas/PTLD using pharmacologic induction of the latent viral TK gene and enzyme in the tumor cells, followed by treatment with ganciclovir. Arginine butyrate selectively activates the EBV TK gene in latently EBV-infected human lymphoid cells and tumor cells. A Phase I/II trial has been initiated, employing an intra-patient dose escalation of arginine butyrate combined with ganciclovir. In six patients with EBV-associated lymphomas or PTLD, all of which were resistant to conventional radiation and/or chemotherapy, this combination produced complete clinical responses in four of six patients, with a partial response occurring in a fifth patient. Pathologic examination in two of three patients demonstrated complete necrosis of the EBV lymphoma, with no residual disease, following a single three-week course of the combination therapy. Possible side-effects of the therapy included nausea and reversible lethargy at the highest doses. One patient suffered acute liver failure, thought to be secondary to release of FasL from the necrotic tumor. Analysis of patient-derived tumor cells in culture demonstrated that arginine butyrate produced selective induction of the EBV TK gene, which then conferred sensitivity to ganciclovir, resulting in tumor apoptosis. Additional patient accrual is sought for further evaluation of this therapy.
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PMID:Epstein--Barr virus post-transplant lymphoproliferative disease and virus-specific therapy: pharmacological re-activation of viral target genes with arginine butyrate. 1149

Lymphoproliferative diseases (LPDs) associated with the Epstein-Barr virus (EBV) include non-Hodgkin lymphomas, which occur in the setting of immunosuppression, including that induced by human immunodeficiency virus, and posttransplant lymphoproliferative disorders. These LPDs are characterized by actively proliferating, latently infected EBV-positive B lymphocytes and often follow a rapidly progressive fatal clinical course. Pharmacologic treatment for herpesvirus infections has targeted the virus-specific enzyme, thymidine kinase (TK), with nucleoside analogs. The lack of viral TK expression in EBV-positive tumors, caused by viral latency, however, makes antiviral therapy alone ineffective as an antineoplastic therapy. Arginine butyrate selectively activates the EBV TK gene in latently infected EBV-positive tumor cells. We have developed a strategy for treatment of EBV-associated lymphomas using pharmacologic induction of the latent viral TK gene and enzyme in tumor cells using arginine butyrate, followed by treatment with ganciclovir. A phase I/II trial, using an intrapatient dose escalation of arginine butyrate combined with ganciclovir, is underway. This combination therapy has produced complete clinical responses in 5 of 10 previously refractory patients, with partial responses occurring in 2 additional patients. This virus-targeted antitumor strategy may provide a new therapeutic approach to EBV-associated neoplasms.
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PMID:Induction of the Epstein-Barr virus thymidine kinase gene with concomitant nucleoside antivirals as a therapeutic strategy for Epstein-Barr virus-associated malignancies. 1155 13

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