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)

There are many case reports of secondary neoplasms occurring after treatment with alkylating agents. A case of malignant melanoma of the glans penis in a chronic myeloid leukemia (CML) Ph'-positive patient after 13 years on busulfan treatment is described. Since neither impairment of immune status nor increased incidence of secondary neoplasm have hitherto been reported in CML, the suggestion that busulfan has a carcinogenetic effect is discussed.
 ...
PMID:Malignant melanoma of the glans penis in a chronic myeloid leukemia patient after busulfan therapy. 348 Nov 41

TCA (T Cell system A) is a di-allelic system of HLA-like antigens encoded by genes located about 15 cM telomeric to HLA-A. In normal individuals, TCA antigens are only expressed on a subpopulation of T cells, the TG lymphocytes. We now report on the expression of TCA on leukemias and other malignancies. An increased proportion of cells carrying the TCA phenotype was encountered in testing peripheral blood lymphocytes from patients with acute lymphoblastic T-cell leukemia (T-ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). In contrast, patients with B-cell malignancies such as chronic lymphatic leukemia (CLL) and hairy cell leukemia (HCL) or non-T/non-B common acute lymphoblastic leukemia (common ALL) had normal proportions of TCA-positive lymphocytes. Quantitatively different levels of TCA expression are found on some melanoma cell lines and others are TCA negative. These variations are independent of the expression of HLA Class I antigens by the same cells. The expression of TCA antigens by malignant nonlymphoid cells suggests that this system may code for differentiation markers, important in the biology of neoplastic transformation.
 ...
PMID:TCA: a polymorphic genetic marker in leukemias and melanoma cell lines. 348 57

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.
 ...
PMID:[Cancer chemotherapy with special reference to pharmacokinetics of nitrosoureas]. 622 95

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.
 ...
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

AMSA, an acridine derivative with significant antitumor activity in experimental tumors, was administered to 17 patients with advanced tumors refractory to standard chemotherapies. A phase I study was undertaken in 10 patients with solid tumors and lymphomas. Dose-limiting toxicity was myelosuppression. With a median dose of 90 mg/m2 (75-148 mg/m2), median lowest WBC count was 1,000/mm3 (100-3,200) on day 11 and its recovery up to 4,000/mm3 was seen on day 21, while lowest platelet count was 42 X 10(3)/mm3 (7-300 X 10(3) on day 12 and its recovery up to 100 X 10(3)/mm3 was on day 20. Non-hematological toxicities were nausea (39%), vomiting (11%) and phlebitis (17%) in 18 courses of therapy. The result indicated that the recommended dose schedule for a phase II evaluation was 90 mg/m2, every three weeks. Therapeutic activity was observed in patients with non-Hodgkin's lymphoma (one partial response and two minor responses out of four). Two out of five breast, one ovarian, and one melanoma patients showed stable diseases. Five leukemic patients (three AMLs, one MoL, and one blastic CML) were treated with AMSA, and in these cases cytoreduction of peripheral and bone marrow blasts was seen, but it was not adequate to induce remission. Further clinical trials with this agent are warranted, especially in patients with acute leukemia, lymphoma and breast cancer.
 ...
PMID:[Phase I-II studies of a new antineoplastic agent, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA)]. 689 58

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.
 ...
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.
 ...
PMID:Vindesine: a new vinca alkaloid. 700 62

In order to ascertain the frequency and distribution of isochromosomes in neoplasia, we surveyed the cytogenetic data from 20,007 tumors with clonal chromosome aberrations reported in the literature. Tumor types for which at least 50 cases with acquired aberrations and 10 cases with isochromosomes had been reported were selected, yielding a total of 18,160 neoplasms. Of these, 1,792 cases (9.9%) displayed a total of 2,014 isochromosomes. The 9 most common isochromosomes (detected in at least 50 cases) were, in decreasing order of frequency, i(17q), i(8q), i(1q), i(12p), i(6p), i(7q), i(9q), i(5p), and i(21q). The frequency of isochromosomes varied among the different tumor types, with the highest incidence in germ cell neoplasms (60%) and the lowest in chronic myeloproliferative disorders (2.3%). Also, the spectrum of isochromosomes differed among the neoplasms. The most common isochromosomes in the different tumor types were i(11q), i(17q), and i(21q) in acute myeloid leukemia; i(9q), i(17q), and i(22q) in chronic myeloid leukemia; i(17q) in chronic myeloproliferative disorders; i(X)(q13), i(17q), and i(21q) in myelodysplastic syndromes; i(7q), i(9q), and i(17q) in acute lymphoblastic leukemia; i(1q), i(7q), i(8q), and i(17q) in chronic lymphoproliferative disorders; i(1q), i(6p), i(9p), i(17q), and i(21q) in Hodgkin's disease; i(1q), i(6p), and i(17q) in non-Hodgkin's lymphoma; i(1q), i(8q), and i(17q) in adenocarcinoma; i(1q), i(3q), i(5p), and i(8q) in squamous cell carcinoma; i(5p), i(8q), and i(11q) in transitional cell carcinoma; i(1q), i(7q), and i(17q) in Wilms' tumor; i(1q), i(12p), and i(17q) in germ cell neoplasms; i(1p), i(1q), i(6p), and i(17q) in sarcoma; i(5p), i(6p), i(7p), and i(21q) in mesothelioma; i(1q), i(6p), and i(17q) in malignant neurogenic neoplasms; i(1q), i(6p), and i(17q) in retinoblastoma; and i(1q), i(6p), and i(8q) in malignant melanoma.
 ...
PMID:Isochromosomes in neoplasia. 752 35

Based on our previous studies demonstrating marked anti-tumor activity of interleukin-2 (IL-2)-activated bone marrow in vitro and in vivo, we studied the generation of anti-tumor cytotoxic effectors from chemotherapy- and growth factor-mobilized PBSC from 12 patients with different solid tumors. As chemotherapy and growth factor priming could lead to important qualitative and quantitative alterations of lymphoid cells, we also looked at the distribution of lymphoid cells contained in primed PBSC. In addition, different variables were defined for successful application of the technique to clinical protocols. The cells were placed in culture at varying cell densities in either serum-containing or serum-free culture medium, supplemented with IL-2, 100 or 1000 Cetus units/ml at 37 degrees C for 24 or 72 h, in flasks or in culture bags. Anti-tumor cytotoxicity was tested against A375 (melanoma), K562 (CML) and Daudi (Burkitt's lymphoma) cell lines in standard 4 h 51Cr release assay. Marked cytotoxicity was seen against all cell lines tested (A375: 32.7% +/- 5.2; K562: 52.8% +/- 4.8; Daudi: 50.5% +/- 7.2). Cytotoxicity was comparable in serum-containing and serum-free culture conditions and in tissue culture flasks and bags. Cell density up to 10 x 10(6)/ml was not associated with any significant decline in cytotoxicity. IL-2 activation of PBSC after thawing led to the generation of cytotoxicity comparable to that obtained with fresh PBSC. On flow cytometric analysis, the proportion of CD8+ T cells and NK cells (CD56+) was found to be higher in primed PBSC than in control peripheral blood mononuclear cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interleukin-2 activation of chemotherapy and growth factor-mobilized peripheral blood stem cells for generation of cytotoxic effectors. 777 9

The effects of sublethal radiation (3 Gy) and anti-asialo GM1 (anti-ASGM1) on engraftment of human tumour cell lines and fresh tumour were evaluated in the severe combined immunodeficient (SCID) mouse. Four tumour cell lines (colonic adenocarcinoma LS174T, malignant melanoma MEWO, lung adenocarcinoma H125, chronic myelogenous leukemia K562) and a fresh colon cancer metastasis were injected subcutaneously, intraperitoneally or intravenously into SCID mice. Tumour volume and metastatic spread of implanted tumours were evaluated 3-8 weeks following inoculation. Pretreatment with radiation and anti-ASGM1 resulted in more rapid and extensive uptake of subcutaneous and intraperitoneal tumours. Tail vein injection into pretreated animals also resulted in a greater number of lung metastases of H125, MEWO and K562 cell lines. This study demonstrates that sublethal radiation and the elimination of murine NK cell activity with anti-ASGM1 improves tumour take rates. These findings should prove useful for investigations of human cancer immunotherapy using SCID mice engrafted with human lymphocytes and human tumours.
 ...
PMID:Improved engraftment of human tumours in SCID mice pretreated with radiation and anti-asialo GM1. 784 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>