Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methotrexate is now used widely for the treatment of acute leukemia, non-Hodgkin's lymphoma, osteogenic sarcoma, choriocarcinoma, breast carcinoma, pulmonary and epidermoid carcinoma, and intrathecal chemotherapy. It is also useful in bone marrow transplantation, severe psoriasis, rheumatoid arthritis, dermatomyositis, Wegener's granulomatosis and sarcoidosis. The recent dramatic intensification of methotrexate therapy can be attributed in part to advances in our understanding of the clinical pharmacology of the folate antagonists, as well as to the combination of positive results and their effective dissemination to medical oncologists. The review summarizes the pharmacologic findings and illustrates how they are currently being applied to the treatment of malignant disease.
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PMID:The clinical pharmacology of methotrexate: new applications of an old drug. 34 86

Whole blood was separated into preparations of erythrocytes, mononuclear leukocytes, polymorphonuclear leukocytes, platelets and plasma. Each preparation was analyzed for the concentration of the polyamines putrescine, spermidine and spermine. This was done in 17 controls, 14 patients with psoriasis, four patients with hereditary elliptocytosis, two patients with chronic lymphocytic leukemia and one patient each with lung cancer, non-Hodgkin's lymphoma, sickle cell anemia with mild psoriasis, and progeria. In patients with elevated blood polyamine levels, absorption onto erythrocytes was relatively common, and the spermine/spermidine ratio was useful in localizing abnormalities and characterizing the nature of the polyamine alteration. Proliferative states were associated with elevated spermine/spermidine ratios relative to controls while this relationship was reversed in erythropathies such as hereditary elliptocytosis and sickle cell anemia.
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PMID:Polyamine compartmentalization in various human disease states. 61 72

The role of selected prior medical conditions in the etiology of hematopoietic malignancies was examined in a case-control study of members of two regional branches of the Kaiser Permanente Medical Care Program (USA). Past history of chronic infectious, autoimmune, allergic, and musculoskeletal disorders was abstracted from medical records for leukemia (n = 299), non-Hodgkin's lymphoma (NHL, n = 100), and multiple myeloma (n = 175) cases and matched controls (n = 787). Little difference was found between cases and controls for most of the chronic conditions evaluated, including sinusitis, carbuncles, urinary tract infections, pelvic infections, herpes zoster, asthma, rheumatoid arthritis, psoriasis, bursitis, and gout. Only three statistically significant elevated risks were found, i.e., with combined disc disease myeloma among patients with prior eczema and disk and other musculoskeletal conditions, and NHL following tuberculosis. Only two of these associations showed consistent patterns by sex and geographic region (myeloma with eczema and with musculoskeletal conditions). While prior history of eczema and musculoskeletal conditions may slightly increase risk of myeloma, this study provided little if any support for an association of chronic infectious, autoimmune, allergic, and musculoskeletal conditions with subsequent occurrence of the leukemias or NHL. Additionally, these data did not support a role for chronic antigenic stimulation, as defined in previous epidemiologic studies, in the etiology of hematopoietic malignancies.
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PMID:Leukemia, lymphoma, and multiple myeloma following selected medical conditions. 152 26

Cyclosporine is not cytotoxic but it inhibits the production of immunologic memory-building growth factors by CD4+ T lymphocytes. It also may have inhibitory effects on the effector phase of certain immune reactions. These inhibitory effects are largely reversible and when treatment is stopped, the immune competence of cyclosporine-treated patients returns to normal. In contrast, conventional cytotoxic immunosuppressive agents tend to exterminate the lymphocyte clones that are activated during therapy, and such clonal deletions may cause permanent loss of immunologic memory to those antigens because T lymphocytes are not readily restored in adults with involuted thymus. Most transplant patients have received cyclosporine in combination with various other immunosuppressive agents, and reports suggest that a combination of this drug and conventional immunosuppressive agents may be associated with increased early appearance of non-Hodgkin's lymphoma and, possibly, endocrine-related tumors. An increase in cancers has not been observed in patients treated with cyclosporine alone for such conditions as psoriasis and autoimmune diseases. Treatment of adults with cytotoxic immunosuppressive drugs may permanently delete T-lymphocyte clones that are required for control of latent oncogenic viruses or certain malignant cells. Because of this, when such patients are treated with cyclosporine, further suppression of T-cell function combined with impairment of cytokine-mediated stimulation of natural killer cells and cytotoxic macrophages may facilitate tumor growth. Consequently, it is predicted that if cyclosporine monotherapy is associated with an increased incidence of tumors, it would primarily affect psoriasis patients who are treated with cyclosporine after PUVA or methotrexate therapy. Eventually, comparison of cancer incidence in different categories of patients should resolve this issue.
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PMID:Immunity during cyclosporine therapy. 227 38

The etiology of keratoacanthomas is unknown, but human papillomavirus (HPV) has been suspected to be involved in the pathogenesis of this lesion because koilocytic changes may be observed and because HPV has been found in cutaneous squamous-cell carcinomas and premalignant keratoses in immunosuppressed patients. We analyzed DNA extracted from 39 keratoacanthomas from 22 "at-risk" patients (nine patients undergoing UV light and/or anthralin therapy for psoriasis, 10 solid organ transplant recipients, one patient with xeroderma pigmentosa, one patient with acquired immunodeficiency syndrome, and one patient undergoing therapy for non-Hodgkin's lymphoma) for the presence of HPV. The results were compared with analyses of DNA extracted from 30 keratoacanthomas from 28 patients at no known increased risk for these lesions. Using polymerase chain reaction (PCR) primers designed to detect multiple HPV types (including 6, 11, 16, 18, 31, and 33), HPV was detected in seven keratoacanthomas from six of the at-risk patients and in eight sporadic keratoacanthomas from eight patients without risk factors. HPV was also present in one of 26 nonlesional skin controls. Statistical analysis showed a significant difference in the prevalence of HPV DNA sequences found in keratoacanthomas compared to normal control skin (p = 0.038). The presence of virus by PCR could not be predicted by histologic evaluation. Sequence analysis showed the presence of HPV types 11, 13, 24, 33, and 57. Although these results confirm the frequent presence of HPV in keratoacanthomas, the role of this virus in the etiology and pathogenesis of these lesions remains to be elucidated.
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PMID:Detection of human papillomavirus DNA in keratoacanthomas by polymerase chain reaction. 905 48

Expression of the lymphocyte homing receptor CD44 and its splice variants have been linked to tumour dissemination and poor prognosis in non-Hodgkin's lymphoma. Specifically, the in vitro expression of variant exon V6 confers metastatic potential in rat pancreatic carcinoma cell lines. In this study, we investigated the expression of CD44 splice variants in cutaneous T-cell lymphomas, including patients with mycosis fungoides (MF), Sezary syndrome (SS), large-cell anaplastic lymphoma (LCAL) and HTLV1-associated cutaneous lymphoma. In addition, 4 involved lymph nodes from 2 patients with MF and 1 patient with SS were examined. Inflammatory dermatoses, lichen planus and psoriasis, and normal skin were also studied. Immunohistochemistry was performed using a panel of monoclonal antibodies, including those with specificity for CD44H (standard isoform) and variant exons V3, V6 and V8-9. Normal epidermal keratinocytes were consistently CD44H and CD44 V3, V6 and V8-9 positive. In all the different clinicopathological subtypes and stages of cutaneous T-cell lymphomas, including involved lymph nodes, tumour cells consistently expressed CD44H, but were CD44 V3 and V6 negative. CD44 V8-9 was expressed on a majority of tumour cells in 2/5 LCAL and on occasional tumour cells in 2/5 LCAL. Occasional V8-9 positive tumour cells were also identified in 6/13 MF, 1/4 SS and 3/4 HTLV1. In 2/3 lymph node samples from 2 patients with tumour-stage MF, CD44 V8-9 expression was found on a small percentage of atypical mononuclear cells. Scattered V8-9 positive dermal mononuclear cells were present in sections of lichen planus and psoriasis. We have found no evidence to suggest that the metastasis-associated CD44 variant exon (V6) is expressed in cutaneous T-cell lymphoma, or that CD44H expression is associated with an adverse prognostic group. It is not clear whether the strong expression of CD44 V8-9 in 2 patients with CD30 positive LCAL reflects activation status or metastatic potential.
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PMID:CD44 variant expression in cutaneous T-cell lymphoma. 924 61

This study was designed to estimate the relative cancer risk of patients with moderate to severe psoriasis, with reference to different treatments. A cohort of 5687 hospitalized patients with psoriasis obtained from the Finnish Hospital Discharge Register in 1973-84 was linked with the records of the Finnish Cancer Registry. Standardized incidence ratios for cancer were calculated by dividing the observed number of cases by the expected cases, which were based on the national sex-specific and age-specific cancer incidence rates. By the end of 1995, 533 cancer cases were observed in the cohort. The overall cancer incidence was increased (standardized incidence ratio 1.3, 95% confidence interval 1.2-1.4). The estimated relative risks were highest for Hodgkin's disease (standardized incidence ratio 3.3, 95% confidence interval 1.4-6.4), squamous cell skin carcinoma (standardized incidence ratio 3.2, 95% confidence interval 2.3-4.4), non-Hodgkin's lymphoma (standardized incidence ratio 2.2, 95% confidence interval 1.4-3.4), and laryngeal cancer (standardized incidence ratio 2.9, 95% confidence interval 1.5-5.0). The role of prior oral antipsoriatic medications or phototherapy on the development of these cancers was assessed in a nested case-control study, for which 67 cases and 199 sex and age matched controls were selected from the psoriasis cohort. The relative risks were estimated using conditional logistic regression analysis. Oral 8-methoxy-psoralen plus ultraviolet-A radiation therapy and the use of retinoids were associated with an increased risk of squamous cell skin carcinoma (relative risk adjusted for the other treatment variables 6.5, 95% confidence interval 1.4-31, and 7.4, 95% confidence interval 1.4-40, respectively), whereas none of the treatments could be linked with the occurrence of non-Hodgkin's lymphoma.
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PMID:Psoriasis, its treatment, and cancer in a cohort of Finnish patients. 1069 22

The relationship between a history of selected medical conditions and risk of lymphomas was investigated in a hospital-based case-control study conducted in Northern Italy on 429 incident, histologically confirmed cases of non-Hodgkin's lymphoma (NHL), 158 cases of Hodgkin's disease (HD) and 1157 controls admitted to hospitals for acute conditions. The odds ratios (OR) for NHL were above unity in patients with a history of infectious mononucleosis (OR 2.9), herpes zoster (OR 1.8), pyelonephritis (OR 4.9), tuberculosis (OR 1.8), malaria (OR 1.9), any chronic bacterial diseases (OR 1.7), rheumatoid arthritis (OR 1.7) and psoriasis (OR 2.5). With reference to HD, the ORs were 4.0 for infectious mononucleosis, 2.9 for herpes zoster, 3.3 for pyelonephritis, 2.3 for tuberculosis, 1.4 for chronic bacterial diseases, 2.4 for rheumatoid arthritis, 2.7 for psoriasis and 2.1 for diabetes. The association of NHL and HD with herpes zoster was restricted to the first ten years since the onset of the disease. The relationships between NHL and mononucleosis (OR 12.9), malaria (OR 2.8) and psoriasis (OR 14.0) were stronger for cases aged > or = 60 years, and that with tuberculosis (OR 3.5) was stronger for younger cases. For HD, the positive association was stronger for cases aged > or = 40 years for herpes zoster (OR 3.8) and diabetes (OR 2.6). An increased risk of NHL was found in association with poliomyelitis (OR 1.6) (restricted to cases aged > or = 60 years, OR 4.0) and BCG immunizations (OR 1.6), but not with vaccination against smallpox, tetanus and diphtheria; increased risks of HD were found in relation to poliomyelitis and BCG immunization in cases aged > or = 40 years (OR respectively 2.5 and 2.1), or > or = 50 years (OR 4.3 and 2.2). Thus, our results confirm the association between a history of several chronic infectious and inflammatory diseases and the risk of NHL or HD, and are compatible with a role of chronic immunological alterations in the aetiology of lymphomas.
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PMID:Medical history and risk of Hodgkin's and non-Hodgkin's lymphomas. 1077 11

Fusion proteins are recombinant molecules that combine a targeting mechanism to a cytocidal moiety. DAB(389)IL-2 (denileukin diftitox; ONTAK), with a unique mechanism of action, is the first genetically constructed fusion protein to reach the clinic. In this molecule, the interleukin-2 (IL-2) gene is genetically fused to the enzymatically active and translocating domains of diphtheria toxin. DAB(389)IL-2 is internalized into IL-2 receptor-bearing cells by endocytosis. The ADP-ribosyltransferase activity of diphtheria toxin is cleaved in the endosome and is translocated into the cytosol where it inhibits protein synthesis, leading to apoptosis. DAB(389)IL-2 and its predecessor, DAB(486)IL-2, have shown clinical activity in a variety of diseases, including B-cell non-Hodgkin's lymphoma, cutaneous T-cell lymphoma (CTCL), Hodgkin's disease, psoriasis, rheumatoid arthritis, and HIV infection. The highest response rates were observed in CTCL, and this became the focus of clinical trials leading to its subsequent approval by the United States Food and Drug Administration for this disease. The potential applications of DAB(389)IL-2 in lymphomas are reviewed.
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PMID:DAB(389)IL-2 (ONTAK): a novel fusion toxin therapy for lymphoma. 1170 18

Recent case reports have raised concerns regarding the risks of non-Hodgkin's lymphoma in patients with inflammatory bowel disease treated with immunosuppressive agents. This evidence-based review examines this issue from data derived from the use of immunosuppression in other conditions (and inflammatory bowel disease). We conclude that, in transplant (cardiac and renal) recipients, immunosuppression increases the risk of non-Hodgkin's lymphoma. For non-transplant patients (with psoriasis and rheumatoid arthritis), debate remains as to whether the observed increase in the incidence of non-Hodgkin's lymphoma is due to drug or disease. For inflammatory bowel disease per se, population studies show no significant increase in the risk of non-Hodgkin's lymphoma, with a relative risk of 1.3 (95% confidence interval, 0.9-1.7) compared to expected rates, and several studies of immuno- suppression in inflammatory bowel disease do not appear to confirm a significant rate of lymphoma incidence. Reported cases of lymphoma from single centres should be viewed with caution as evidence of increased risk. If any association exists, it is likely to be of minimal clinical significance compared to the established and more frequent risks of myelosuppression and infection, and is unlikely to outweigh the benefit of immunosuppression in inflammatory bowel disease.
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PMID:Review article: does the use of immunosuppressive therapy in inflammatory bowel disease increase the risk of developing lymphoma? 1173 13


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