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)

O6-Methylguanine was measured by a competitive repair assay in blood leukocyte DNA of seven patients with Hodgkin's or non-Hodgkin's lymphoma during therapeutic exposure to procarbazine involving three daily p.o. doses (50 mg each) for 10 days (corresponding to 2.1 mg/kg/day for a 70-kg human). Adduct accumulation was observed in all seven cases, reaching levels up to 0.28 fmol/microgram of DNA (0.45 mumol/mol of guanine). In one individual, maximal levels of adduct were reached after 7 days of exposure, followed by a steady decline, whereas in all other individuals continuous accumulation was observed throughout the exposure period. In four individuals for which data were available for Day 11 (12 to 16 h after the final intake of procarbazine), decreased amounts of O6-methylguanine were observed relative to the last previous measurements. The accumulation of O6-methylguanine was linearly correlated (P less than 0.01) with the cumulative dose of procarbazine, with a slope of 0.011 fmol of O6-methylguanine/microgram of DNA per mg/kg of body weight or 2.68 x 10(-4) fmol of O6 methylguanine DNA per mg/m2. (Two h after the administration of single p.o. doses of 1 to 10 mg/kg of procarbazine to rats, O6-methylguanine formation in leukocyte DNA was just under half that in liver DNA and showed a linear relationship with dose with a slope of 0.017 fmol/microgram of DNA per mg/kg of body weight or 5.67 x 10(-4) fmol of O6-methylguanine/microgram of DNA per mg/m2. A negative correlation (P less than 0.05) between the rate of accumulation of O6-methylguanine in different individuals and lymphocyte O6-alkylguanine-DNA alkyltransferase (AGT) was observed, demonstrating a probable protective effect of AGT against the accumulation of O6-methylguanine during exposure to methylating agents. This observation supports the suggestion of a possible role of procarbazine-induced O6-methylguanine in the pathogenesis of acute nonlymphocytic leukemia appearing after treatment with chemotherapeutic protocols which include procarbazine, based on the finding of low lymphocyte AGT levels in patients with such therapy-related neoplastic disease (Sagher et al., Cancer Res., 48: 3084-3089, 1988). Lymphocyte AGT levels were mainly in the range of 5 to 10 fmol/micrograms of DNA and showed no consistent variation during procarbazine exposure.
 ...
PMID:Accumulation of O6-methylguanine in human blood leukocyte DNA during exposure to procarbazine and its relationships with dose and repair. 232 2

Hematological and cytogenetic characteristics of 75 cases of therapy-related acute non lymphoid leukemia (t-ANLL) occurring in Hodgkin's disease (HD) are analysed in this multi-institution study. Combined radio and chemotherapy had been given in 88 per cent of patients, either as adjuvant (44 per cent) or as salvage modality (44 per cent). Radiotherapy alone and chemotherapy alone had been given in 3 per cent and 9 per cent respectively. Eighty per cent of patients were in remission of HD and 71 per cent off-therapy while developing leukemia. The median latent time from remission of HD to leukemia was 34 months. The myeloblastic variety of leukemia accounted for 43 per cent of total cases; the myelomonocytic and monocytic for 17 per cent and 4 per cent, the promyelocytic and erythroblastic variants for 5 per cent and 7 per cent of t-ANLL. Twenty four per cent of cases were unclassifiable; one of these was TdT-positive. Dysplastic features of erythrocytic line were invariably present with circulating erythroblasts; defects of granulocytes, circulating megathrombocytes and micromegakaryocytes were also present. Bone marrow hypoplasia and marked fibrosis were documented in 47 per cent and 30 per cent of cases. Preleukemia heralded overt leukemia in 73 per cent of cases; 37 per cent had refractory anemia with no excess of blasts; 16 per cent of preleukemias were unclassifiable. Cytogenetics revealed chromosome abnormalities in 83 per cent of cases; 72 per cent presented chromosome 5 and/or 7 monosomy or partial deletion (5q- or 7q-) of the long arm (94 per cent in the combined modality therapy group). In 3 cases, a pure monosomy 7 was observed; in none 5q-alone. Response rate to conventional therapy was 14 per cent; low and high-dose cytarabine were of little benefit. Long-term CR (28 + and 16 + months) was achieved in 2 cases with allogeneic bone marrow transplantation (BMT) as first-line therapy. A better knowledge of t-ANLL in HD and new therapies, including BMT, may improve the prognosis of this late complication of intensive HD treatment.
 ...
PMID:Treatment-related leukemia in Hodgkin's disease: a multi-institution study on 75 cases. 243 31

Chemotherapeutic agents such as procarbazine, which produce methylated bases in DNA, are used to treat many Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) patients. A small proportion of such patients develop secondary malignancy. We examined the possibility that those patients who develop secondary malignancy have low endogenous levels of O6-alkylguanine DNA alkyltransferase (AGT) activity and are therefore more sensitive to the mutagenic and carcinogenic effects of their treatment. We assayed AGT activity in peripheral blood lymphocytes from patients with HD, NHL, acute nonlymphocytic leukemia (ANLL) de novo, and therapy-related ANLL, as well as a group of normal control subjects. Studies in normal controls showed that at least over a short term of 1 week, individuals have characteristic AGT levels, although some individuals sampled repeatedly over several months showed high variation. Mean AGT activities +/- SE for the various groups studied were (fmol/micrograms of DNA): normal control group, 7.05 +/- 0.36; HD and NHL patients (prior to treatment), 4.97 +/- 0.42; HD-NHL patients receiving procarbazine, 3.88 +/- 0.44; ANLL de novo, 7.78 +/- 1.72; and therapy-related ANLL, 4.30 +/- 0.58. AGT activity decreased in the peripheral blood lymphocytes of some individuals taking procarbazine. The mean AGT activity in the procarbazine-treated patients was low, as was the activity for the therapy-related ANLL patients.
 ...
PMID:Low O6-alkylguanine DNA alkyltransferase activity in the peripheral blood lymphocytes of patients with therapy-related acute nonlymphocytic leukemia. 245 85

Aggressive, multimodal treatment of Hodgkin's disease has led to dramatic increases in survival but not without significant early toxicity and late complications. The most serious late complication is the development of a secondary neoplasm. These secondary cancers include acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, and various solid tumors.
 ...
PMID:Second neoplasms in Hodgkin's disease: current controversies. 266 29

Although open lung biopsy (OLB) is frequently employed for diagnosis of pulmonary lesions in patients with Hodgkin's disease, the actual efficacy of the procedure in establishing a diagnosis in these patients, and its effect on their treatment and clinical outcome, have not been evaluated. We reviewed the results of OLB in 41 patients with previously diagnosed Hodgkin's disease (17 with stage II disease, 10 with stage III, and 14 with stage IV) who had pulmonary opacification on chest roentgenogram. Nineteen (46%) diagnoses were specific and 22 nonspecific. The most common specific diagnosis was Hodgkin's disease (12 patients); the others were Pneumocystis carinii pneumonia (3), solitary fungal granuloma (2), cytomegalovirus pneumonia (1), and primary lung adenocarcinoma (1). Specific diagnoses were made in 11 (69%) of 16 patients with discrete nodules or masses but in only eight (32%) of the 25 patients with non-nodular radiographic opacification. Eleven (58%) of 19 patients who were asymptomatic or had had symptoms for longer than 4 wk had specific diagnoses, compared to one of six patients (17%) symptomatic for 1 wk or less. Survival of hospitalization correlated more with stage of Hodgkin's disease than with specific diagnosis. However, treatment was changed after biopsy in 22 (54%) of the patients. The results suggest that OLB can be helpful in the management of patients with Hodgkin's disease and pulmonary infiltrates, both in establishing a diagnosis and in assisting the patients' management. OLB appears to be more helpful in patients with Hodgkin's disease than in patients with acute nonlymphocytic leukemia or the acquired immunodeficiency syndrome and pulmonary infiltrates.
 ...
PMID:Open lung biopsy in patients with Hodgkin's disease and pulmonary infiltrates. 271 53

391 patients treated intensively for Hodgkin's disease were followed for up to 15 years to evaluate the risk of therapy-related acute non-lymphocytic leukaemia (t-ANLL) and preleukaemia. Only two independent factors, patient age and cumulative dose of alkylating agents, were related to the risk of t-ANLL. The hazard rate of t-ANLL was roughly proportional to the square of patient age and to the total cumulative dose of alkylating agents. In 320 patients treated with alkylating agents the cumulative risk of t-ANLL increased steadily from 1 year after the start of treatment and reached 13.0% (SE 3.0) at 10 years after which time there were no further cases. Calculated from cessation of therapy with alkylating agents, however, the cumulative risk curve increased steeply during the first 1-2 years then gradually levelled out and no new cases were observed beyond 7 years. With a 15-year follow-up the general risk of solid tumours was not increased.
 ...
PMID:Risk of therapy-related leukaemia and preleukaemia after Hodgkin's disease. Relation to age, cumulative dose of alkylating agents, and time from chemotherapy. 288 81

Myelodysplastic syndromes and acute leukemias after treatment for Hodgkin's disease (HD) are well recognized. Preleukemic changes are commonly seen. Three patients from the authors' files are found with myelofibrosis and bone marrow lymphocytosis after treatment for HD. Although somewhat unusual, the clinical impression initially was, in each case, isolated recurrence of HD involving the bone marrow, 6 to 11 years after initial diagnosis. In each case, after single or multiple marrow aspirates and biopsies were done, the differential between HD involving the marrow and myelodysplasia with myelofibrosis and lymphocytic infiltrates was made. The absence of diagnostic Reed-Sternberg (RS) cells was useful in diagnosing the latter. All three patients died of causes related to cytopenias, with two having progressed to overt acute nonlymphocytic leukemia. Myelofibrosis with lymphocytic infiltrates in the marrow, without diagnostic RS cells, in patients' status after treatment for HD, should alert one to the possibility of myelodysplasia.
 ...
PMID:Myelodysplasia with bone marrow lymphocytosis and fibrosis mimicking recurrent Hodgkin's disease. 275 Jul 3

Simultaneous involvement of bands 8p11 and 16p13 in a primary, even though rare, chromosomal translocation recently described in acute nonlymphocytic leukemia may be of crucial interest in some subtypes of this acute leukemia, particularly in the monocytic form. In the present report we describe this translocation in acute nonlymphoblastic leukemia FAB M4, possibly secondary to Hodgkin's disease, though it is also possible that the leukemia may have developed de novo. The aberration t(8;16)(p11;p13) was present in 100% of direct and cultured bone marrow cell preparations. A very high frequency of cells with nonclonal structural chromosome aberrations was also observed in peripheral blood cultures (more than 53%). Random translocations and deletions constituted most of the observed alterations. These findings are discussed with regard to the relationships between secondary leukemias and intensive polychemotherapeutic treatments of primary neoplasias.
 ...
PMID:Translocation t(8;16)(p11;p13) in acute nonlymphoblastic leukemia (M4) possibly secondary to Hodgkin's disease. 291 27

Receptor binding and biological effects of insulin and insulin-like growth factors I and II (IGF I/II) were assessed in three human malignant cell lines: a Burkitt-type ALL-cell line, a ANLL-cell line and a Hodgkin's disease-cell line. Insulin receptor binding could be demonstrated in Burkitt-type ALL cells and ANLL cells, whereas no insulin receptor binding was detectable in Hodgkin cells. IGF I and IGF II binding could be demonstrated in all leukemic cells. Insulin stimulated glycogen synthesis in the insulin receptor bearing cell lines. DNA synthesis was stimulated by insulin, IGF I and II. IGF I was more active in stimulating DNA synthesis than IGF II.
 ...
PMID:Human leukemic cells: receptor binding and biological effects of insulin and insulin-like growth factors. 294 75

A review of the Memorial Sloan-Kettering Cancer Center experience with second malignancies (SM) after childhood Hodgkin's Disease (HD) identified 17 SM in 320 patients who survived more than 1 year from, and were 15 years old or younger at the time of, HD diagnosis (1949 to 1983). Of 254 previously untreated patients, 12 SM were noticed as compared with 0.606 expected on the basis of rates in the general pediatric population (relative risk, 19.8; 95% confidence interval, 10.2 to 34.6). For patients who received multi-agent chemotherapy, the cumulative probability of developing acute nonlymphocytic leukemia (ANLL) or bone sarcoma was 6.2% and 5.5%, respectively, at 10 years from the initiation of therapy; the cumulative risk of all SM in this group reached 18.7% at 15 years. For patients who received radiation alone or with single-agent chemotherapy, the cumulative risk of SM rose from 0% at 10 years and 2% at 15 years, to 10.7% at 25 years from the initiation of treatment. The risk of ANLL after childhood HD was highest in the first 5 to 10 years after combined modality treatment, and aggressive forms of NHL were associated with excessive immunosuppression. Bone sarcomas predominated in solid SM in the first decade after HD treatment, whereas "adult-type" cancers, for example, breast and colon carcinomas, were more delayed. Our findings, supported by a literature review, point to a therapy-related enhanced risk of approximately age-appropriate solid SM. This possibility mandates careful surveillance of long-term survivors of childhood HD.
 ...
PMID:Second malignancies after childhood Hodgkin's disease. The Memorial Sloan-Kettering Cancer Center experience. 304 37


<< Previous 1 2 3 4 5 6 7 Next >>