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)

Twelve patients with bone marrow necrosis were diagnosed in our hospital during the past thirteen years. All were related to malignant tumors. Bone marrow metastatic carcinoma was diagnosed in 5, suspicious metastatic carcinoma in 3, acute leukemia in 2, chronic granulocytic leukemia in 1 and malignant histiocytosis in 1. In case 1, the necrosis was secondary to gastric cancer metastasis into the bone marrow and complicated by microangiopathic hemolytic anemia; in case 3, bone marrow necrosis was the initial manifestation and a diagnosis of acute lymphocytic leukemia was finally confirmed; in case 4 of acute monocytic leukemia, bone marrow necrosis followed intramedullary chemotherapy and in case 5, marrow necrosis was secondary to chronic granulocytic leukemia. These four manifestations mentioned above have not been reported yet at home. Three cases examined by systemic 99mTe bone scan suggest that 99mTe bone scan be useful in the diagnosis of marrow necrosis. In this paper, the causes, diagnosis, treatment, prognosis and pathogenesis are discussed.
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PMID:[Bone marrow necrosis and malignant tumors]. 345 26

Bone marrow macrophages were found to express tartrate-resistant acid phosphatase (TRAP) under pathological conditions. In chronic granulocytic leukemia and metastatic carcinoma in the bone marrow this phenomenon was striking, all or almost all of the marrow macrophages being reactive. In other conditions, such as hypertransfusion or chemotherapy-induced marrow aplasia, the phenomenon did occur but was clearly a minor one. These observations indicate that tissue macrophages may become TRAP positive under the effect of unknown stimuli operating in certain pathological conditions. The results further suggest that the synthesis of the isoenzyme of acid phosphatase resistant to tartrate inhibition is a marker of macrophage activation rather than of differentiation towards particular subsets of the mononuclear phagocyte system.
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PMID:Expression of tartrate-resistant acid phosphatase in bone marrow macrophages. 348 85

We reviewed 2110 bone marrow aspirations from the same number of patients to establish the incidence and associations of peripheral and bone marrow basophilia. Of these, 125 cases of marrow basophilia (5.9% incidence) and 63 cases of peripheral basophilia (3.0% incidence) were identified. There were 33 patients with simultaneous marrow and peripheral basophilia, which was only significantly associated with chronic myelogenous leukemia (24 cases). Isolated peripheral basophilia was rarely seen (30 patients, 1.4% incidence) and it did not reflect any significant pathologic association. Marrow basophilia was significantly present in chronic myeloproliferative disorders, idiopathic myelodysplasia, certain erythrocyte disorders, such as iron deficiency anemia, and aplastic anemia. The incidence of marrow basophilia in patients with lymphoma, acute leukemia, or solid carcinoma was not significantly different from what it would be as a chance occurrence. Our findings suggest that marrow basophilia is a specific, but not sensitive, marker of myeloproliferative and dysmyelopoietic syndromes.
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PMID:Incidence and clinical significance of peripheral and bone marrow basophilia. 350 57

Recombinant human IL-2, secreted by yeast harboring a plasmid containing a synthetic IL-2 gene, is biologically active in augmenting human natural killer (NK) cell activity. A dose-dependent linear stimulation of NK activity was obtained against the chronic myelogenous leukemia cell line K562 over the range 3 to 300 units/ml of IL-2. Enhancement of NK activity was similarly demonstrable against the less NK-sensitive carcinoma cell lines LoVo and SKOSC. IL-2 could also be demonstrated to augment antibody-dependent cellular cytotoxicity (ADCC) against SKOSC targets. IL-2 responsiveness segregated with a non-E-rosetting fraction comprising 11% of postfractionation lymphocytes and containing 94% of the recoverable NK activity, suggesting that IL-2 might operate directly upon the NK cell rather than through an accessory cell. This is believed to be the first demonstration of NK stimulatory activity by the product of a totally synthetic human IL-2 gene. The availability, purity, and NK-enhancing properties of the recombinant IL-2 make it a potentially important agent for clinical trial.
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PMID:Modulation of human natural killer cell activity by recombinant human interleukin 2. 387 64

A total of 72 cell conditioned media (CCM) were screened for their ability to stimulate colony formation by human granulopoietic progenitor cells. Granulocyte-macrophage (GM) colony-stimulating factor(s) (CSF) were found in CCM of nine tumor cell lines, two primary urinary bladder tumors, and three epithelial cell cultures of normal urinary tract. The most active medium came from urinary bladder carcinoma cell line 5637. CSF released by the 5637 cell line induced dose-dependent GM colony formation from human fetal, normal adult, and CML bone marrow (BM) and from mouse BM. Human fetal and normal adult BM formed more colonies when stimulated with 5637 CCM than with peripheral blood leukocyte (PBL) feeder layers, while CML BM produced more colonies with PBL feeder layers. CCM from 5637 was more active in stimulating GM colony formation than human placenta conditioned medium (PCM) and PHA-LCM. 5637 CCM produced in serum-free hormone-supplemented medium was nearly equipotent and can serve as suitable starting material for purification.
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PMID:Elaboration of granulocyte-macrophage colony-stimulating factor by human tumor cell lines and normal urothelium. 387 49

Recombinant human IL-2, secreted by yeast harboring a plasmid containing a synthetic IL-2 gene, is biologically active in augmenting human natural killer (NK) cell activity. A dose-dependent linear stimulation of NK activity was obtained against the chronic myelogenous leukemia cell line K562 over the range of 3 to 300 units/ml of IL-2. Enhancement of NK activity was similarly demonstrable against the less NK-sensitive carcinoma cell lines LoVo and SKOSC. IL-2 could also be demonstrated to augment antibody-dependent cellular cytotoxicity (ADCC) against SKOSC targets. IL-2 responsiveness segregated with a non-E-rosetting fraction comprising 11% of postfractionation lymphocytes, and containing 94% of the recoverable NK activity, suggesting that IL-2 might operate directly upon the NK cell rather than through an accessory cell. This is believed to be the first demonstration of NK stimulatory activity by the product of a totally synthetic human IL-2 gene. The availability, purity, and NK-enhancing properties of the recombinant IL-2 make it a potentially important agent for clinical trial.
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PMID:Modulation of human natural killer cell activity by recombinant human interleukin 2. 388 Nov 92

Two hundred and thirty-six cases of multiple primary cancer associated with hematological malignancies, collected from 35 medical institutions in Japan, are reported. Based on the time interval between the first cancer and the second cancer, they were divided into three groups: synchronous cancer (94 cases), metachronous cancer subsequent to hematological malignancy (61 cases) and metachronous hematological malignancy subsequent to carcinoma (76 cases). The most common initial cancers were acute leukemia (including atypical leukemia and erythroleukemia), non-Hodgkin's lymphoma, multiple myeloma and chronic myelogenous leukemia of the hematological malignancies, and gastric cancer of the carcinomas. Patients with cancer of the uterus and breast in the metachronous cancer group metachronously developed hematological malignancies more frequently than those in the synchronous cancer group. Multiple primary cancer was observed more frequently in men than in women both in the synchronous cancer group and in the group with metachronous cancer subsequent to hematological malignancies. Acute leukemia was the most frequent disease type in incidence among the metachronous hematological malignancies. This secondary acute leukemia was characterized by a mostly granulocytic nature, poor response to chemotherapy and poor prognosis.
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PMID:Multiple primary cancers associated with hematological malignancies. 400 83

A brilliant, coarsely granular nuclear antigen was detected by anti-complement immunofluorescence in the nuclei of acute myeloid leukemia myeloblasts. Designated as LANA (leukemia-associated nuclear antigen), the reactivity differs from that of the Epstein-Barr-virus-determined nuclear antigen (EBNA) in immunological specificity and morphological appearance, although it is visualized by the same method. Serum from acute myeloid leukemia patients gave positive reactions in 73% of the cases. In acute lymphatic leukemia, chronic myeloid leukemia, chronic lymphatic leukemia, and Burkitt's lymphoma the sera were positive in 35, 14, 19, and 24%, respectively. Two of five polycythemia and two of eleven myeloma sera were also positive. Among 61 healthy controls, 58 were negative, whereas three showed a diffuse nuclear staining with a different pattern. Among 24 carcinoma patients, 18 were negative, whereas six gave a nuclear staining with a different, diffuse pattern. Sera from 20 patients who had recovered from infectious mononucleosis were all negative. In addition to the blasts of acute myeloid leukemia, a similar reactivity was seen with two Epstein-Barr virus DNA and EBNA-negative African lymphoma biopsies and in a short-lived tissue culture line derived from one of them. LANA could be a fetal or tissue-specific antigen, a virally determined antigen, or a specific form of anti-nuclear reactivity.
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PMID:Human leukemia-associated anti-nuclear reactivity. 459 70

This paper provides an overview of cancer chemotherapy with special reference to the pharmacokinetics of the nitrosoureas. At physiological PH, the chloroethylnitrosoureas can be decomposed into an isocyanate and 2-chloroethyl diazene hydroxide. Therefore, it is clear that they have both alkylation and carbamoylation actions. In addition to the spontaneous chemical dissociation, the nitrosoureas can be metabolized by liver microsomal enzymes to more polar hydroxylated products, and certain nitrosoureas can be denitrosated by these enzymes to the parent urea. Since the lipid-soluble nitrosoureas and some of the water-soluble nitrosoureas such as ACNU and MCNU demonstrated to cross the blood-brain barrier, they have been used in the treatment of primary brain tumors and tumors and tumors of metastatic origin. It has been demonstrated from the results of our study and other reports that the alkylation of DNA by ACNU progresses more slowly as compared with that of other alkylating agents. This is an important finding in relation to the appearance of delayed myelosuppression of the nitrosoureas and in the design of dose schedules of these agents. The major clinical emphasis has been directed towards the more active chloroethylnitrosoureas with reduced myelosuppression, and attempts are now made for this purpose. Unfortunately, the results of phase I and II trials of the newly developed nitrosoureas suggest that these agents produce delayed and cumulative bone marrow toxicity. Antitumor activity of the nitrosoureas is frequestly observed in chronic myelocytic leukemia, malignant lymphoma, brain tumors and small cell carcinoma of the lung, and less frequently in gastrointestinal carcinoma, multiple myeloma and malignant melanoma. In order to enhance clinical effects of the nitrosoureas, further investigation of the design in therapeutic schedules on the basis of their pharmacokinetic characteristics will be needed.
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PMID:[Cancer chemotherapy with special reference to pharmacokinetics of nitrosoureas]. 622 95

The results of three phase II clinical trials with three new analogues belonging to the family of nitrosoureas are reported. One of the studied agents, chlorozotocine (CZT) is American, while the other two, RFCNU and RPCNU, are French. All three drugs have a sugar radical. CZT proved effective mainly in a few cases of leukemia and in one case of blastic transformation of chronic myelocytic leukemia. RFCNU was shown to be effective in 8% of digestive tumors, in 1 out of 7 pancreatic cancers and in 3 out of 10 hepatic and pulmonary metastases from an undiscovered primary adenocarcinoma. As for RPCNU, it's action resembles that of RFCNU: tumor regression lasting for over three years was obtained in a patient with hepatic metastases from a digestive carcinoma; in another patient a regression rate exceeding 50% was seen in pulmonary metastases from a rectal tumor. One of the significant results of our study is the apparent tissular specificity of responses according to the agent given: CZT is more often efficient on the lymphatic localizations of the studied tumors (4/5 responses); RFCNU and RPCNU often proved active on hepatic metastases (17% responses). Digestive tolerance was excellent with CZT and RFCNU and not quite as satisfactory for RPCNU. As predicted by our experimental study, platelet toxicity is both less common and less severe with RFCNU than with CZT and RPCNU.
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PMID:[Phase II study of 3 new nitrosoureas, 1 American (chlorozotocin) and 2 French (RFCNU and RPCNU)]. 629 62


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