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)

In patients with Hodgkin's disease the excretion of pyrimidine deoxyribonucleosides in urine was followed up within the course of 92 chemotherapeutical series with cytostatics of COOP group. In 14-day chemotherapy series, the excretion of deoxycytidine, deoxyuridine, thymidine, and their sum was significantly increased. In this paper the results are analyzed and a possibility of utilization of this finding for the judgment in the clinical course of the disease is considered.
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PMID:Deoxypyrimidineuria in the course of chemotherapy in M. Hodgkin. 100 61

The authors have followed the excretion of pyrimidine doexyribonucleosides in the urine of patients with generalized stages of Hodgkin's disease. They proved an increased excretion of deoxyuridine and thymidine in these patients compared to healthy persons. In the course of 14-days of combined chemotherapy a statistically significant increase in the excretion of DNA catabolites followed was found.
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PMID:Urine excretion of nucleosides in Hodgkin's disease treated by combined chemotherapy. 113 91

The intracellular purine and pyrimidine ribonucleotide concentrations were determined in lymphoid cells from peripheral blood of 16 patients with chronic lymphocytic leukaemia (CLL) and from peripheral blood and/or lymphoid tissue of 18 patients with non-Hodgkin lymphoma (NHL). Compared to normal peripheral lymphocytes, the lymphoid cells from CLL patients contained lower, and those from NHL patients higher amounts of nucleotides. The lymphoid cells of NHL patients showed an imbalance in the nucleotide pool compared to either normal resting peripheral or proliferating tonsillar lymphocytes. The lymphoid cells of patients with CLL showed an imbalance only when compared to normal, resting peripheral lymphocytes. The abnormalities in the nucleotide pools involved decreased ratios of purine:pyrimidine, adenine:guanine and uracil:cytosine nucleotides. Lymphocytes from CLL and NHL patients contained increased amounts (relative and/or absolute) of UDP sugars, and NHL lymphocytes also showed a changed composition of the UDP sugars. Analysis of the ribonucleotides in the lymphoid cells provides useful information for the differential diagnosis of patients suspected of having CLL or NHL, and may be valuable for the design of new chemotherapeutic regimens.
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PMID:Aberrant ribonucleotide pattern in lymphoid cells from patients with chronic lymphocytic leukaemia or non-Hodgkin lymphoma. 361 Mar 88

The activity of dCMPase has been measured in cell extracts from human lymphoproliferative disorders. The highest levels occurred in T helper-CLL and Thy-ALL, but high levels were also found in C-ALL, NPDLL transforming to DHL, DPDLL and DHL. A range of enzyme activities was found in the majority of types examined, with the widest range encountered in ALL, NPDLL and DHL. In DWDLL, a narrow range of dCMPase activities was found, with enzyme levels in the control range or moderately increased. Similarly, B-CLL exhibited a narrow range of enzyme activities, within that of the controls. The highest enzyme activity in HD was found in the highly malignant type - lymphocyte depleted HD. Statistically significant differences were found between the distribution of dCMPase activities in ALL and the chronic leukemias; and between favorable histologic types of non Hodgkin's lymphomas and the unfavorable DHL type. These data suggest that dCMPase activity is a marker of the clinical aggression of human lymphoid malignancies. Moreover, the marked variation in enzyme activity in each type of lymphoid malignancy suggests that this also applies to individual tumors as well. In view of the important role of dCMPase in pyrimidine metabolism and the profile of enzyme activities in leukemia and lymphoma, it is suggested that an inhibitor of dCMPase could be of clinical value in lymphoid malignancy.
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PMID:Deoxycytidylate deaminase activity in lymphoproliferative disorders. 670 Feb 60

In patients with morbus Hodgkin, treated primarily by the actino- and chemotherapy, the excretion was followed of DNA catabolites (deoxycytidine, deoxyuridine, thymidine and their sum) in the course of the therapy. The dynamics was studied of changes in the time interval of interest and attention was paid to its relation to the clinical and histological type of disease and to the successful character of the therapy defined by reaching a complete remission. The group of patients as a whole was characterized by an increased excretion of catabolites in the time interval of interest. No dependence was demonstrated between the catabolite excretion and extent of the disease similarly as between the excretion and successful character of the therapy. The dynamics of the changes in the time intervals of interest was neither remarkably nor continuously increased or decreased. The test of the excretion of pyrimidine deoxyribonucleosides possesses sufficient sensitivity for demonstrating laws in relation to the therapy during group evaluation. With respect to individual variability of values of particular patients and to the absence of the relations mentioned above the test is not suitable to indicate the individual response to the anticancer therapy.
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PMID:Individual changes of DNA catabolite excretion in the course of antitumor therapy of Hodgkin's disease. 736 28

Brequinar (DUP 785, NSC 368390) is a 4-quinoline carboxylic acid derivative with broad spectrum antitumour activity in experimental models that acts as an antimetabolite by specific inhibition of de novo pyrimidine synthesis. We performed a phase I study of brequinar administered as a 10 min intravenous (i.v.) infusion for 5 consecutive days, every 4 weeks. 67 evaluable patients were entered in this study and a total of 130 courses were administered at doses ranging from 2 to 350 mg/m2. The dose-limiting toxicity was myelosuppression with predominant thrombocytopenia. Myelosuppression was dose-related and non-cumulative, with considerable interpatient variability depending on haematological risk factors. The maximum tolerated dose of brequinar was 210 mg/m2/day in poor risk patients whereas patients with good risk haematological profile tolerated higher doses (up to 350 mg/m2/day). Other non-limiting toxicities included nausea and vomiting, mucositis and skin reactions. Brequinar plasma pharmacokinetic profiles were biphasic with alpha half-life ranging from 0.1 to 0.7 h, and beta half-life ranging from 1.5 to 8.2 h. Increase in brequinar area under the plasma concentration versus time curves (AUC) was nonlinear. Day 5 brequinar pharmacokinetics obtained in 21 patients indicated a significant increase in AUC (47%) and half-life beta (133%) compared to day 1 pharmacokinetics in the same patient. Brequinar plasma AUC and the per cent change in platelet count at nadir were correlated (P < 0.001). Although no objective response was observed in this study, one minor response was noted in cervical lymph nodes of a Hodgkin's disease patient.
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PMID:Phase I and pharmacokinetic study of brequinar (DUP 785; NSC 368390) in cancer patients. 849 53

The LAZ3/BCL6 gene on chromosome 3q27 is recurrently disrupted in B-cell non Hodgkin's lymphomas by translocations involving immunoglobulin genes or other chromosome regions. We have studied the t(3; 11) (q27; q23) translocation, present in a B-cell leukemia cell line (Karpas 231). As a consequence of this translocation, a LAZ3 chimeric transcript was created by fusion, 5' to the LAZ3 exon 2, with a transcribed sequence identical to BOB1/OBF1, a B cell-specific coactivator of octamer-binding transcription factors, recently described. Nucleotidic sequence of a nearly full-length cDNA of the BOB1/OBF1 gene revealed particular features in the 3' untranslated region of the gene, including pyrimidine-rich sequence repeats, an Alu motif, and a polymorphic [CCTT] tetranucleotide microsatellite. Two A to G transition mutations were also detected in the coding region of one allele of a lymphoma B-cell line, Raji, leading to 2 amino-acid changes in the C-terminal region. Due to its cell-specificity and role as a coactivating transcription factor, chromosomal translocation and/or perhaps point mutation of BOB1/OBF1 may contribute to B cell tumorigenesis.
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PMID:Fusion of the LAZ3/BCL6 and BOB1/OBF1 genes by t(3; 11) (q27; q23) chromosomal translocation. 857 89

Gemcitabine is a pyrimidine analogue that showed significant activity in solid malignancies. Gemcitabine acts by inhibiting DNA synthesis through chain termination and ribonucleotide reductase inhibition. During initial phase I and II studies, gemcitabine had a low toxicity profile and was well tolerated as a single agent and in combination therapy. Recently, there has been more interest in studying the activity of gemcitabine in hematologic malignancies. Gemcitabine demonstrated good activity in refractory Hodgkin disease patients, non-Hodgkin lymphoma, cutaneous T-cell lymphoma, and acute leukemias. There is a preponderance of evidence on the activity of gemcitabine in vitro in myeloma and leukemic cell lines. The activity of gemcitabine in these disorders will pave the way for incorporating this agent into the early phases of therapy.
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PMID:Gemcitabine in hematologic malignancies. 1167 93

The nucleoside 5-fluoro-2-deoxyuridine is a pyrimidine analogue accumulating in proliferative cells. We prospectively evaluated biodistribution of the PET tracer [(18)F]5-fluoro-2-deoxyuridine (FdUrd), its value for imaging malignant tumors, and its correlation to both [(18)F]2-fluoro-2-deoxyglucose (FDG)-PET findings and histological proliferation indices. In 11 previously untreated patients (5 lung carcinoma; 3 soft tissue sarcoma; 2 gastrointestinal carcinoma; 1 non-Hodgkin lymphoma [NHL]), mean doses of 290 MBq FdUrd and 390 MBq FDG were administered intravenously on subsequent days. Static PET scans were initiated 50-70 min after administration and the mean standardized uptake values (SUV) were calculated. Dynamic emission FdUrd scans were performed in 8/11 patients. Time-activity curves of blood and tumors as well as SUV of tumor lesions and organs were calculated. Proliferative activity was evaluated by Ki-67 immunohistostaining of biopsies. Tracer accumulated physiologically in liver, kidney, and bladder. SUVs were: kidney, 4.8 +/- 0.66; liver, 4.1 +/- 0.36; vertebrae, 0.70 +/- 0.17; spleen, 0.37 +/- 0.06; lungs, 0.19 +/- 0.05; femora/humeri, 0.14 +/- 0.03. Five patients exhibited significant intratumoral FdUrd-uptake (2 sarcomas; 1 NHL; 2 lung carcinomas) with mean SUVs ranging from 0.7 to 10.5. Metastases were not detected. Time-activity curves showed a rapid initial increase of intratumoral activity followed by activity retention. FDG-PET was positive in 10/11 patients. Correlation between the SUV of FdUrd-PET and FDG-PET or the tissue proliferation index, respectively, was not significant. FdUrd was a suitable tracer for imaging malignant tumors only in exceptional cases: Sarcoma, NHL, and some lung carcinomas were detected. FdUrd-PET was less effective than FDG-PET. In this group of patients, it was not useful in measuring tissue proliferation.
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PMID:[18F]5-fluoro-2-deoxyuridine-PET for imaging of malignant tumors and for measuring tissue proliferation. 1295 20

The most impressive regressions obtained to date with the use of chemotherapy are in metastatic choriocarcinoma of females. In the management of Hodgkin's disease, leukemia, and lymphoma, chemotherapy is a useful and accepted form of therapy. In many cases radiation and chemotherapy are interdependent. In disseminated carcinomas arising in the lung, ovary or breast, there is less likelihood of significant improvement with the use of chemotherapy, but if the disease is not amenable to radiotherapy, useful palliation can be obtained at times. While newer chemotherapeutic agents for cancer, notably the pyrimidine analogues, have a broader spectrum of antitumor effects than others investigated earlier, they should be regarded as providing a valuable research stimulus in the continued search for more effective and less toxic agents.
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PMID:Current concepts of cancer chemotherapy. 1448 58


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