Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A possible causal association between chromosome structural change and neoplastic transformation has long been mooted, particularly since chromosomal changes occur frequently in the cells of a variety of malignancies. Only in recent years, however, has the evidence in support of this contention begun to appear convincing, and this has followed from the application of developments in cytogenetic techniques. The advent of methods for revealing specific bands in the human metaphase complement has enabled all the chromosomes and many chromosomal regions to be unambiguously identified, and the recent application of prophase banding methods gives further improvements in resolution. With these techniques, specific constitutional chromosomal deletions or translocations have been discovered in inherited cases of retinoblastoma (del.13q14), Wilms' tumour with aniridia (del.11p13) and renal-cell carcinoma (t(3:8) (p21:q24)), in which each of the chromosomal changes appears to be a dominant factor in inheriting a predisposition to a tissue-specific tumour. A heritability for cancer predisposition is also associated with the inherited chromosomal instability syndromes of Bloom's, Fanconi's anaemia and ataxia telangiectasia, although specific chromosomal changes have not been reported to be associated with the neoplasms in such individuals, except in some cases of lymphoma and leukaemia in ataxia telangiectasia. Specific chromosomal translocations have, however, been recorded in a variety of malignancies, with a particular involvement of chromosomes 22, 14, 8, 15, 17 and 21. However, although many hundreds of patients with the specific 9/22 rearrangement seen in chronic myeloid leukaemia and also those with the 14/8 rearrangement in Burkitt's, and other, lymphomas have been described, no single case in which these rearrangements were present as constitutional changes has been reported. The possible nature of the changes seen at the cytogenetic level in terms of gene content of the chromosomes involved is discussed.
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PMID:Cytogenetics of heritability in cancer. 629 35

In the mouse, retrovirus B and C are causal agents of mammary cancer and leukemia, respectively. In previous work it was demonstrated that sera of leukemia-lymphoma patients possess antibodies which react with antigenic determinants of Type C virus present on AKR-lymphoma and AKR-thymus targets. The object of this paper was to determine whether these antibodies also reacted with Type B viral antigens present on a virus-induced BALB-mammary carcinoma; at the same time a comparative study was carried out with sera of breast cancer patients. A total of 325 sera were obtained from 277 leukemia-lymphoma cases under protocol treatment: 232 acute lymphoid leukemia, 23 acute myeloid leukemia, 15 chronic myeloid leukemia and 55 Hodgkin lymphoma sera. A total of 240 sera were obtained from breast cancer patients at the time of diagnosis and 196 sera from normal blood donors served as controls. Using indirect immunofluorescence with labeled anti-human IgG and the murine targets, antibodies were encountered in a high percentage of cancer cases and were consistently absent in normal sera. The results confirm the presence of antibodies reacting with murine Type C virus in leukemia-lymphoma cases and indicate the presence of antibodies reacting to both Type B and C retroviruses in the sera of breast cancer patients.
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PMID:Antibodies presumably cross-reacting with mouse retrovirus type B and C in the sera of both leukemia-lymphoma and mammary cancer patients. 631 22

Procoagulant activity of gastric cancer tissues and leukocytes obtained from various types of leukemia have been studied with special reference to TTP. The following results were obtained. Homogenates of APL leukocytes and gastric cancer tissues contained strong procoagulant activities, most of which have been identified as TTP since the activities were neutralized by a specific antibody against purified human placenta TTP, inactivated by the removal of phospholipid with heptane-butanol mixture, and inactivated by the addition of phospholipase C. The delipidated homogenates regained procoagulant activities by relipidation procedures. These results also confirmed that TTP from APL leukocytes and gastric cancer tissues have the same lipoprotein properties as those of TTP in normal tissues. Though slight proteolytic activity and fibrinolytic activity were demonstrated in the homogenate of gastric cancer tissues, it was noted that the TTP activity was different from these two activities by partial purification of TTP from gastric cancer tissues. The TTP activity of 9 homogenates of gastric cancer tissues was 301 +/- 289 (mean +/- SD) units per mg protein, being higher in homogenates of mucinous adenocarcinoma and signet-ring cell carcinoma than in those of tubular and poorly differentiated adenocarcinoma. The mean TTP activity of leukocyte homogenates from 14 patients with APL and one out of 4 patients with CML in blastic crisis was 81 +/- 76 units/10(7) cells. The TTP activity of the homogenates of leukocytes from 7 out of 18 patients with AML and another patient with CML in blastic crisis ranged from one to six units/10(7) cells with a mean of 3.3 +/- 1.2. The TTP activity of leukocyte homogenates from the other 11 cases of AML, two cases of CML in blastic crisis, 6 cases of CML, and one case each of ALL and CLL were less than one unit/10(7) cells. In leukemic patients, all cases with a value of more than 202 for the product of units of TTP activity per 10(7) cells and differential count (%) of leukemic cells in the bone marrow smear (MU value) were accompanied by DIC. The MU value of leukemic patients correlated well to the plasma fibrinogen and serum FDP levels. All patients with a MU value of more than 277 died of DIC when a sufficient amount of heparin was not administered. On the other hand, no DIC developed in any of the patients with a MU value of less than 90.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of tissue thromboplastin in the development of DIC accompanying neoplastic diseases. 666 48

A group of 40 Sprague-Dawley rats was exposed to 100 ppm benzene for 6 h/day, 5 days/week for life. Another group of 40 rats received air under the same exposure regimen. During the exposures, treated rats exhibited continuously depressed peripheral erythrocyte and lymphocyte counts. Although the incidences of these peripheral cell depressions were statistically significant, the magnitudes of the depressions were not. Histopathologic evaluation revealed that splenic hemosiderin pigments were much more prevalent in exposed rats than in controls, indicating either red cell hemolysis or ineffective erythropoiesis. The mortality-corrected tumor incidences between exposed and control mice were not statistically different. However, several exposed rats died with tumors that, because of their rare spontaneous incidence, are most likely treatment-related. Four rats died with liver tumors, two died with zymbal gland carcinoma, and one died with chronic myelogenous leukemia.
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PMID:Evidence for hematotoxicity and tumorigenesis in rats exposed to 100 ppm benzene. 673 44

The clinical effects of 10-deaza-aminopterin, an inhibitor of dihydrofolate reductase with a better therapeutic index against several murine tumors than that of methotrexate, were examined during the course of a phase I study in patients with advanced malignant neoplasms. Three escalating dose schedules were explored: single iv injections once daily, single iv injections twice weekly, and continuous infusion. The maximum tolerated doses were: single injections at a dose of 7 mg/m2/day for 5 days; single injections at a dose of 15 mg/m2 twice weekly for four to six doses; and continuous infusion at a dose of 3 mg/m2/day for 5-6 days in patients with solid tumors and until bone marrow hypoplasia in patients with leukemia. Mucositis was dose-limiting in all schedules. Occasionally, mild leukopenia, thrombocytopenia, and skin rash were noted. A minor antitumor response was seen in a patient with gallbladder carcinoma. Marked leukemic cell kill was observed in several patients with acute leukemia or blastic phase of chronic myelogenous leukemia. Disease-oriented phase II trials are planned at this Center for several tumor varieties.
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PMID:Phase I trial of 10-deaza-aminopterin in patients with advanced cancer. 682 21

A potential application of the human tumor stem cell colony assay is to guide Phase II clinical investigations by identifying classes of tumors (or individual patients) which are sensitive in vitro to a new antitumor compound. We have tested human tumor stem cells from 140 tumor biopsies representing 20 different tumor types for chemosensitivity to the Phase II drug 4'-(9-acridinylamino)methanesulfon-m-anisidide. In vitro sensitivity was defined as a reduction in the number of tumor colony-forming cells to 30% of the control or less after a 1-hr exposure to one-tenth of the pharmacologically achievable plasma concentration of 4'-(9-acridinylamino)methanesulfon-m-anisidide. In vitro sensitivity was found in 29 cases: non-Hodgkin's lymphoma (2 of 2); cervical carcinoma (1 of 1); sarcoma (3 of 6); neuroblastoma (1 of 2); acute myelogenous leukemia (6 of 16); chronic myelogenous leukemia (1 of 3); melanoma (8 of 34); uterine carcinoma (1 of 5); lung carcinoma (1 of 9); ovarian carcinoma (4 of 36); and breast carcinoma (1 of 11). Prospective in vitro-in vivo correlations in eight patients with various tumor types showed that three of three patients sensitive in vitro to 4'-(9-acridinylamino)methanesulfon-m-anisidide responded in vivo, while five of five patients resistant in vitro had no clinical response. The results provide support for further evaluation of the utility of the human tumor stem cell colony assay for targeting Phase II clinical trials.
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PMID:In vitro chemosensitivities of human tumor stem cells to the Phase II drug 4'-(9-acridinylamino)methanesulfon-m-anisidide and prospective in vivo correlations. 689 12

A case of acquired dyserythropoiesis with inter-erythroblastic connections is reported in a patient with chronic myeloid leukaemia, developing a terminal acute hepatic failure related to hepatocarcinoma. The erythroblastic series was abundant but only made of clusters grouping 10 to 20 closely adherent cells. The cellular membranes showed linear junctions or were interdigitated and the intercellular space was occupied with electron dense ferritin granules. This non specific aspect of dyserythropoiesis may be related to the hepatic carcinoma, which was probably induced by busulfan therapy.
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PMID:Acquired dyserythropoiesis with abnormal intercellular contacts between erythroblasts. Report of a patient with chronic myeloid leukaemia and hepatocarcinoma. 693 42

Surface marker analyses and TdT assays were performed on cells from 31 patients. A variety of diagnoses were made and categorized as follows: acute leukemia (group I), non-Hodgkin lymphoma (group II) and diverse diagnoses (group III). Levels of TdT in the range from 0 to 7.9 U/mg lyophilized blasts from the peripheral blood were found in AL. This corresponds to 0-95 U/10(8) cells. Preparations of mononuclear cells from the peripheral blood of healthy donors showed TdT values up to 0.88 U/mg or 10.6 U/10(8) cells. High TdT activity was observed in a patient with AML, type M1 according to the FAB classification. In a patient with ALL (L1) cytostatic treatment effected the clearance of TdT activity from the peripheral blood cells and at the same time induced a significant increase of E rosette forming cells. Combined studies of the TdT activity and cell surface markers may enable us to define remissions and relapses of AL more precisely than it is possible by conventional cytological methods. Within the group II two patients with moderate TdT activities of 1.2 and 1.28 U/mg, respectively, were observed whose cells were of prolymphocytic or unclassifiable appearance, respectively. The TdT assay may be helpful to identify such cells of unknown origin and in addition may provide the means of discrimination between such cases and ALL patients who mostly show high TdT activities. Another result of our studies was the finding of moderate TdT activity of 1.2 U/mg with cells from the pleural effusion of a patient with Hodgkin's disease. Cells from malignant effusions from a patient with melanoma and a patient with teratoid carcinoma showed no TdT activity. Cells form the peripheral blood and from the bone marrow of a patient with blast crisis of CML showed TdT activity of 1.52 and 2.72 U/mg, respectively. Two other patients with blast crisis were negative. Not TdT activity was found in leukemic plasma cells. Our results show that lyophilized cells can be used for determinations of TdT activity. This greatly facilitates multi-parameter studies including cytological, cell surface marker and biochemical analyses.
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PMID:Terminal deoxynucleotidyl transferase (TdT) and membrane receptors in human leukemia and lymphoma -- first experience with lyophilized cells. 694 60

Vindesine (VDS) is an analogue of the vinca alkaloids. Its spectrum of antitumoral activity is similar to that of vincristine (VCR), but with milder experimental neurotoxicity, and it inhibits the polymerization of tubulin. Its terminal half-life is 24 h and its plasma clearance is intermediate between those of vinblastine (VLB) and VCR. The maximal tolerated dose is 4-5 mg/m2/week, the dose-limiting toxicity being myelosuppression (nadir by days 7-8 and recovery by days 11-13). It has already been demonstrated as efficient in childhood acute lymphoid leukemia (ALL), non-Hodgkin's lymphoma, blastic crisis of chronic myeloid leukemia, and esophageal carcinoma. It has also shown activity in Hodgkin's disease, breast and germ cell carcinomas, and melanoma. Intolerance is mainly neurologic, with paresthesias, without motor impairment, or hematologic, with leukopenia, and sometimes alopecia, asthenia, and muscle pains. The results are better if the patients have not been treated previously; continuous infusion could be of interest and there appears to be no cross-resistance with its parent VCR, as documented in ALL.
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PMID:Vindesine: a new vinca alkaloid. 700 62

The usefulness of optimized and newly elaborated histochemical methods for proteinases is illustrated on two selected substances. DAP IV (Gly-Pro-MNA,FBB,pH 7.2) was discovered in 39% and DAP II (Lys-Ala-MNA,FBB,pH 5.5) in 60% of the lymphocytes of human peripheral blood (ly). The reaction product of such ly differs in quality and quantity. On the ultrastructural level, the reaction product of DAP IV (Gly-Pro-MNA,HNF) was found in cell membranes and lysosomes. Enzyme activity in other areas was probably suppressed during the preparation procedure. Although the number of ly revealed with Lys-Pro-MNA and Phe-Pro-MNA at pH 5.5 and with Lys-Pro-MNA at pH 7.2 is high, these substrates do not distinctly discriminate DAP IV and DAP II. DAP IV occurs exclusively in T lymphocytes. The number of DAP IV-positive ly was not decreased in patients with myelofibrosis, plasmacytoma, chronic granulocytic leukemia, or tricholeukemia. It was, however, greatly reduced in chronic lymphatic leukemia (CLL). In patients with malignant lymphomas other than CLL, ly presence is related to the stage of the disease. Decreased values indicate a more severe stage or a relapse. In the majority of patients with gastric cancer DAP IV-positive ly were decreased. They were normal or increased in patients with peptic ulcer. The assessment of the number of DAP IV-positive ly is a simple method that provides information regarding the condition of patients with malignant lymphomas and gastric carcinoma. Neutrophilic leukocytes and their precursors, and to a lesser extent monocytes, are revealed when N-acetyl-Met-I-naphthyl ester (Ac-Met-N) is used as substrate. Membrane-bound lysosomal and cytosol proteinases were investigated together with disaccharidases in jejunal biopsies of patients with malabsorption syndrome. Activities of all enzymes were affected in patients with celiac disease. According to their impairment enzymes could be arranged: Lactase(L). trehalase (T), brush border endopeptidase (BBEP), gamma-glutamyl transferase (GGT), DAP IV, enzyme(s) cleaving Ac-Mer-N, aminopeptidase A, cytosol peptidases and aminopeptidase M. In the propria, DAP IV is decreased or absent, while GGT and, particularly, DAP II are increased. After a gluten-free diet, activities are restored in a reverse order. BBEP and GGT are useful as auxiliary parameters in the assessment of the damage or differentiation degree of enterocytes. DAP IV is a sensitive indicator of the involvement of the propria.
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PMID:Proteinases in pathology. Usefulness of histochemical methods. 701 84


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