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)

Table 6 is a summary of the organisms discussed with a listing of the environmental source, the endogenous source, the predisposing factors including neoplasms, and the postulated mechanisms by which the organism can gain access to the circulation. The evidence considered indicates that the entrance of one of these microorganisms into the bloodstream of a human being depends on the presence of multiplicity of predisposing factors. In the majority of cases of bacteremia due to one of these unusual organisms, two or more predisposing factors are present. Certain predisposing factors, such as cancer chemotherapy or intravenous catheterization, often provide a barrier break, while others, such as liver disease, may render the host immune system less capable of clearing organisms from the circulation. For organisms such as Campy-lobacter, Listeria, and Salmonella spp., attributes that allow the invasion of a healthy host are present and seem to be enhanced by the simultaneous presence of a predisposing condition, such as liver disease, in the host. Although somewhat fragmentary, a number of individual case reports describe bacteremia due to one of these organisms occurring weeks to years after surgery and after other therapeutic measures had effected a supposed cure of a cancer. It may be speculated that cancer patients, even after a cure, are still susceptible to bloodstream invasion by one of the aforementioned organisms by virtue of the presence of one or more predisposing metabolic, physiologic, or immunologic factors, even though these factors may be cryptic. The predominance of hematologic malignancies among cases of bacteremia due to these unusual organisms is also apparent. Although, as pointed out by Keusch (169), the reduction in the performance of immune function in hematologic malignancies compared with solid tumors is likely to be responsible, other associations of certain organisms with specific neoplasms warrant further examination. The frequency of bloodstream infections of Salmonella typhimurium and Capno-cytophaga canimorsus in Hodgkin's disease patients seems likely due to a particular mechanism which infection by these species is favored. The specific nature of these mechanisms remains to be determined. The recovery of any unusual bacterium from blood should warrant a careful consideration of the possibility of underlying disease, especially cancer. Microbiologists should advise clinicians of the unusual nature of the identified organism and provide the counsel that certain neoplastic processes, often accompanied by neutropenia, render the human host susceptible to invasion by almost any bacterium. The recovery of such organisms as C. septicum or S. bovis should prompt the clinician to aggressively seek to identify an occult neoplasm if one has not yet been diagnosed.
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PMID:Recovery of uncommon bacteria from blood: association with neoplastic disease. 755 69

Although combination chemotherapy has had a significant impact on survival for malignancies such as Hodgkin's disease, testicular cancer, and childhood acute leukemias, the majority of cancers are either initially resistant to chemotherapy (renal, colon, etc.) or are initially chemosensitive but acquire resistance during treatment, such as lymphoma and breast cancer. Resistance to chemotherapy remains an obstacle to the successful treatment of human cancer and has been the subject of numerous investigations aimed at identifying the molecular mechanisms of resistance in cancer cells. An improved understanding of the mechanisms by which tumor cells develop resistance to chemotherapy may not only enhance the activity of cytotoxic therapy in advanced malignancies but may ultimately improve the impact of adjuvant therapy, potentially resulting in prolonging disease-free intervals and survival. In this review, therefore, we discuss our current understanding of the MDR1 gene, encoding P-glycoprotein, which is responsible for one mechanism of multidrug resistance (MDR). We also review the evidence supporting the clinical relevance of the MDR1 gene and clinical trials aimed at reversing MDR-mediated resistance. Although MDR-mediated drug resistance has been well characterized in preclinical models, its role in clinical drug resistance is not as well characterized and requires further investigation. Prospective studies are necessary to establish the role of MDR1 gene expression in the clinical resistance. The ability to identify tumors with increased MDR1 gene expression has several potential applications (for example, the prediction of response to chemotherapy and the design of studies aimed at reversal of resistance with agents that inhibit MDR-mediated drug efflux). The initial goal of such trials is to demonstrate the ability to reverse MDR1-mediated drug resistance in the appropriate advanced refractory malignancies. Ultimately, it will be important to incorporate these reversal strategies in the treatment of early-stage disease, at which time the tumor burden is smaller and fewer mechanisms of resistance may be present. Prospective phase I, II, and III clinical trials using reversing agents in conjunction with chemotherapy in malignancies that express the MDR1 gene, such as the hematologic malignancies and breast cancer, are necessary before routine use of agents such as verapamil, quinidine, and cyclosporine, which carry innate toxicities. MDR is a mechanism of drug resistance that provides the potential for an alteration in drug efflux, which may have a significant impact on response and possibly result in improved survival for some cancer patients.
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PMID:Clinical reversal of drug resistance. 760 Aug 45

The protein p27KIP1 belongs to a recently identified family of proteins termed cyclin-dependent kinase inhibitors (CDKIs). These proteins play an important role in regulating cell-cycle progression and loss of their function has been implicated in tumorigenesis. Transforming growth factor beta (TGF-beta) may induce cell growth arrest through p27 activation. TGF-beta often loses its ability to arrest growth of transformed cells; this could potentially occur through a defect in p27. To determine the role of p27 in tumorigenesis, we examined its mutational status in 74 non-Hodgkin's lymphomas (NHLs) (52 of B-cell phenotype, 22 of T-cell phenotype), 5 lymphoma cell lines, and 42 adult T-cell leukemias/lymphomas (ATLs) using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and Southern blot analyses. A nonsense mutation (stop codon) that could result in expression of a truncated nonfunctional p27 protein was detected at codon 76 in one case of acute lymphomatous ATL, but not in matched normal tissues. Previously undescribed polymorphisms were also identified at codon 109 in the lymphomas and at codon 55 in the ATLs. Two homozygous deletions of the p27 gene were detected in one case of B-immunoblastic NHL and in one case of acute ATL by Southern blot hybridization. These results indicate that p27 gene alterations are rare events in NHLs and ATLs, but may play an important role in the pathogenesis of some hematologic malignancies.
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PMID:Alterations of the p27KIP1 gene in non-Hodgkin's lymphomas and adult T-cell leukemia/lymphoma. 765 21

Interleukin-4 (IL-4), originally identified as a B-cell growth factor, has been shown to inhibit certain stages of hematopoietic stem cells. Recently, IL-4 has been recognized as a negative regulatory factor in the growth of hematologic malignancy. In myeloid leukemias, IL-4 can suppress the growth of growth factor-dependent leukemic blast cells derived from acute myelogenous leukemia (AML). IL-4 also suppresses the growth of chronic myelomonocytic leukemia cells through inhibiting the "autocrine" production of IL-6 or granulocyte/macrophage colony-stimulating factor. In lymphoid malignancies, IL-4 can inhibit the proliferation of neoplastic cells from Ph1-positive acute lymphoblastic leukemia, non-Hodgkin's B-cell lymphoma, and multiple myeloma. Thus, IL-4 is expected to be useful as a therapeutic agent for these hematologic malignancies.
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PMID:The role of interleukin-4 in the negative regulation of leukemia cell growth. 768 64

Epstein-Barr virus encoded RNA's (EBER) are small RNA species found in cells latently infected by the virus. The physiological function of these molecules is currently a matter of speculation. Nonetheless, their presence in extremely high copy number has made it possible to reliably detect the Epstein-Barr virus by in-situ hybridization, in human tissues routinely fixed with formalin and embedded in paraffin. Such studies have enhanced our understanding of a number of hematologic malignancies, particularly Hodgkin's disease, angiocentric immunoproliferative lesions and angio-immunoblastic lymphadenopathy. In addition, sequential EBER in-situ hybridization studies on lymphoid tissues should enable oncologists to monitor the development of lymphoproliferative disorders occurring in the setting of organ transplantation, AIDS and hereditary immunodeficiencies.
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PMID:EBER gene expression in Epstein-Barr virus-associated hematopoietic neoplasms. 806 83

Immunosuppressed individuals are at high risk for the development of hematologic malignancies. The typical lymphomas arising in organ transplant recipients are B-cell non-Hodgkin's lymphomas that contain Epstein-Barr virus (EBV) DNA sequences. We investigated the characteristics of posttransplant lymphomas that lacked expression of the usual markers associated with EBV transformation. We describe four large-cell lymphomas seen recently at our institution. Two of these four cases were CD4+, one was CD8+, and in one staining for CD4 and CD8 expression was not performed. One CD4+ lymphoma was a CD30+, EBV- large-cell lymphoma from a 65-year-old kidney transplant recipient, the second was an EBV+ large-cell lymphoma from a 25-year-old heart transplant patient. Two T-cell lymphomas were EBV+ and had clonal T-cell receptor beta gene rearrangements. The other two lymphomas expressed T-cell markers CD4 and CD43, and lacked expression of B-cell markers CD19, CD20, CD21, CD22, CD23, and surface Ig. Both CD4+ lymphomas were tumorigenic after their heterotransplantation into severe combined immunodeficient (SCID) mice. Cytogenetics, immunophenotyping, and genotyping of the secondary tumors from SCID mice showed their clonality and identity with the patients' primary tumors. Novel CD4+ lymphoma cell lines, LH521/4 and LK418/4, were established from tumors that had been passaged in SCID mice. An immunodeficient environment may facilitate the growth of these T-cell or biphenotypic lymphomas; the etiology of their genesis can include transformation with EBV and other, as yet unidentified mechanisms.
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PMID:Characterization of posttransplant lymphomas that express T-cell-associated markers: immunophenotypes, molecular genetics, cytogenetics, and heterotransplantation in severe combined immunodeficient mice. 810 Jul 21

CD30 has been extensively studied as a cell surface marker expressed by Reed-Sternberg cells of Hodgkin's disease and other hematologic malignancies, although little is known about its expression by normal lymphoid cells. We therefore characterized the requirements for the induction of CD30 expression and identified the subsets of T cells that express CD30. CD30 is inducible on approximately 15% of normal PBMC stimulated with any of a variety of nonspecific T cell activators, including PHA, Con A, anti-T11(2) + T11(3), and anti-CD3; ionomycin alone induced lower percentages of CD30+ T cells (3 +/- 2%) compared to other stimuli. Maximal numbers of CD30+ cells were observed at 48 to 72 h of activation and the addition of rIL-2 did not affect these kinetics. However, CD30 expression was enhanced by the addition of exogenous rIL-2 to any of the stimuli tested, although rIL-2 alone did not lead to CD30 expression. The induction of CD30 during anti-CD3 mitogenesis was completely inhibitable by anti-IL-2 antibodies and partially inhibitable by rIL-4, indicating a requirement for both TCR triggering and IL-2 for its expression. Dual immunofluorescence analysis revealed that CD30+ cells were confined to CD3+ T cells that coexpressed higher levels of the p55 IL-2 receptor (CD25) than the CD30- population. Furthermore, CD30 expression was restricted to a subset of cells derived from CD45RO+ T cell precursors. Cell cycle analysis showed that CD30+ expression was not cell cycle dependent. Cross-linking of membrane CD30 induced Ca2+ in TCR+, but not TCR- Jurkat T cells. These results demonstrate that CD30 can serve as a T cell signal-transducing molecule and expressed by a unique subset of activated CD45RO+ T cells.
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PMID:CD30 is a signal-transducing molecule that defines a subset of human activated CD45RO+ T cells. 810 64

87 patients underwent bone marrow transplantation (BMT) in Innsbruck between 1983 and 1992. 81 patients were suffering from hematologic malignancies and severe aplastic anemia and six patients had advanced solid tumours/sarcoma. 56% of the patients undergoing HLA-identical sibling BMT were in an advanced or refractory stage of disease at the time of BMT. 19 patients underwent autologous BMT and 5 patients received a graft from an HLA-matched unrelated donor. Patients were treated with standard conditioning regimens according to the underlying disease. Cyclosporine A (CsA) was given prophylactically against graft-versus-host disease (GVHD) either alone or in combination with methotrexate. Probability of survival for patients transplanted in the first chronic phase of chronic myelogenous leukemia (CML) was 85%, whereas the disease free survival (DFS) for patients transplanted in accelerated phase or blast crisis was only 40%. DFS for acute myelogenous leukemia (AML) in first complete remission and acute lymphoblastic leukemia (ALL) standard-risk (i.e., first or second complete remission) was 71% and 60%, respectively. All patients transplanted for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease had refractory or advanced disease. Probability of survival for lymphoma patients was 60%. Acute GVHD > grade II developed in 35% of patients undergoing HLA-identical sibling BMT (46% in the high-risk group vs. 21% in the standard-risk group). Main causes of death in the high-risk group were relapse (31%), severe bacterial or fungal infections (17%), interstitial pneumonia (11%) and acute GVHD (6%).
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PMID:[Innsbruck results of bone marrow transplantation in treatment of hematologic neoplasms and solid tumors]. 819 54

p53 mutations are found in a wide variety of cancers, including hematologic malignancies. These alterations apparently contribute to development of the malignant phenotype. We analyzed a large series of lymphoid (330 cases) and a smaller series of myeloid (29 cases) malignancies of childhood for p53 mutations by single-strand conformational polymorphism (SSCP) following polymerase chain reaction. Samples with abnormal SSCP were reamplified and analyzed by direct sequencing method. p53 mutations were detected within the known mutational hotspots (exons 5 to 8) in 8 of 330 lymphoid malignancies, and in none of 29 myeloid malignancies, showing that the frequency of p53 mutations in childhood lymphoid malignancies was very low (8 of 330 cases [2%]). Four of these patients had very aggressive, fatal acute lymphocytic leukemia (ALL). None of 13 infants and none of 48 patients with T-lineage leukemia had detectable p53 mutations in their ALL cells. Exceptionally, p53 mutations were comparatively frequent in a small sample of B-cell non-Hodgkin's lymphomas (2 of 8 cases). Mutations were detected in samples from two patients with ALL at relapse; these were not detected in samples at initial diagnosis from the same patients, suggesting that p53 mutations may be associated with progression to a more malignant phenotype. Seven of eight alterations of p53 were missense mutations, and seven of eight samples may be heterozygous for the mutant p53, indicating that p53 protein may act in a dominant negative fashion.
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PMID:Analysis of p53 mutations in a large series of lymphoid hematologic malignancies of childhood. 821 5

The unusual occurrence, protein manifestations, and often devastating consequences of toxoplasmosis in patients with cancer emphasize the need for clinical acumen in the diagnosis and management of this disorder. Toxoplasmosis in patients with cancer has most commonly been described in association with Hodgkin's disease. It has also been reported, usually in the setting of treatment with antineoplastic agents, in patients with other lymphoproliferative disorders, hematologic malignancies, and solid tumors. In this review, among patients for whom the diagnosis was made early enough to begin specific treatment, conditions of 68% improved; this finding was in marked contrast to the severe morbidity and mortality observed for untreated individuals. The high mortality in the untreated group reflects the general debilitation and severe immunocompromise of these patients. Therefore, although toxoplasmosis contributed to a poor prognosis, it was not necessarily always the proximate cause of death.
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PMID:Toxoplasmosis in patients with cancer. 827 8


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