Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma hCT levels were less than 50 pg/ml in 50 normal subjects. In 16 patients with medullary carcinoma of the thyroid (MCT), plasma hCT levels were distinctively elevated and they fell significantly after total thyroidectomy, but in 11 of them plasma levels were still high, indicating the presence of metastases. In 74 patients with the other types of malignancy, plasma hCT levels were found to be high in 9 cases (3 oat cell carcinoma of the lung, 4 malignant carcinoids, one malignant pheochromocytoma and one acute myelocytic leukemia). Except for the leukemic case, all these tumors were derived from neural crest. In 12 patients with primary hyperparathyroidism, plasma hCT levels were less than 20 pg/ml. In 13 hypoparathyroid patients, two with pseudohypoparathyroidism and one with pseudoidiopathic hypoparathyroidism, plasma hCT levels were slightly elevated. Some patients with uremia had elevated plasma hCT levels, but there was no relation between plasma levels of hCT and those of PTH, urea nitrogen or creatinine. In response to Ca (4.5 mg/kg/10 min) or tetragastrin (4 mug/kg/5 min) infusion, a marked increase in plasma hCT was observed in all patients with MCT, but not in normal subjects. In 5 hypoparathyroid patients, a significant increase to both stimuli was also observed in all cases. Two patients with pseudopseudohypoparathyroidism responded to the Ca load. These results indicate that the determination of plasma hCT levels especially after a short Ca or tetragastrin infusion is important to study various pathological conditions.
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PMID:Plasma human calcitonin (hCT) levels in normal and pathologic conditions, and their responses to short calcium or tetragastrin infusion. 19 Dec 50

Candida lusitaniae associated with infection in a patient with acute myelogenous leukemia developed resistance to amphotericin B during systemic treatment of the patient. The organism, when isolated initially, was inhibited by 0.31 mug of amphotericin B per ml in yeast nitrogen base agar, but when isolated (20 days later) just antemortem and postmortem, required 100 and 50 mug/ml, respectively, for complete inhibition at 48 h.
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PMID:Development of resistance to amphotericin B in Candida lusitaniae infecting a human. 29 Mar 51

Peripheral blood lymphocytes (PBL) from normal human donors were sensitized in vitro against allogeneic human acute myelocytic leukemia (AML) cells by means of an unidirectional mixed lymphocyte-tumor cell culture (MLTC) technique. The cytotoxic responsiveness of the sensitized lymphocytes, as determined in vitro by the 51Cr-release assay, varied among individual lymphocyte donors and was greatly dependent on the sensitization culture conditions. Induction of cytotoxic effector cells was augmented appreciably by adding to the cultures minute amounts of the immunopotentiating agent MER-BCG. Responding lymphocytes and stimulating leukemia cells cryopreserved for several weeks in liquid nitrogen were as effective as fresh cells in generating effector lymphocytes; the cytotoxic capacity of already sensitized lymphocytes was fully retained by cryopreservation. The implications of these findings for possible clinical employment of in vitro sensitized lymphocytes in adoptive immunotherapy of cancer are discussed.
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PMID:In vitro induction of cytotoxic effector cells against human neoplasms. I. Sensitization conditions and effect of cryopreservation on the induction and expression of cytotoxic responses to allogeneic leukemia cells. 38 44

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%), when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.
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PMID:Autologous bone marrow transplantation in relapsed adult acute leukemia. 40 Jun 85

The effect of morphine and cocaine on the transport of hydrolyzed nitrogen mustard (NH2-OH) and choline by peripheral blood cells of normal subjects and patients with chronic lymphocytic leukemia, acute lymphoblastic leukemia, and acute myeloblastic leukemia was determined. Transport of HN2-OH by lymphocytes from normal individuals and patients with chronic lymphocytic leukemia was stimulated by morphine and cocaine and, in each case, the effect was statistically significant (P less than 0.05 or greater). However, choline transport by normal lymphocytes was not altered by cocaine and was only slightly stimulated by morphine; choline transport by lymphocytes from patients with chronic lymphocytic leukemia was not stimulated by either morphine or cocaine. HN2-OH and choline transport by cells from patients with either acute lymphoblastic or myeloblastic leukemia was stimulated to a comparable degree by both drugs. Stimulation of HN2-OH transport by morphine and cocaine was greater in normal lymphocytes than in acute leukemic cells and the differences were highly significant (p less than 0.001). Conversely, stimulation of choline transport was more marked in acute leukemic cells than in normal lymphocytes, and these differences were also highly significant (p less than 0.001). It was previously shown that transport of nitrogen mustard by normal and leukemic human cells was biphasic in nature, consisting of a choline-independent component at "high" drug concentrations and a choline-dependent system at "low" substrate concentrations. The preferential stimulation of the low-dose, choline-dependent system by morphine and cocaine in acute leukemic cells relative to that observed in normal lymphocytes suggests a possible mechanism of increasing the therapeutic index of nitrogen mustard.
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PMID:Drug-induced stimulation of transport of hydrolyzed nitrogen mustard and choline by normal and leukemic human cells in vitro. 106 33

Stored autologous haemopoietic cells may be used to repopulate the bone marrow of patients in the advanced stages of different leukaemias who have received cytotoxic drugs. We have used a continuous flow blood cell separator to collect peripheral blood leucocytes from patients with chronic granulocytic leukaemia (CGL) before treatment. We also collected bone marrow cells from patients with CGL and from patients with acute myeloid leukaemia in complete remission. The collected cells were frozen at I degree C per minute using dimethyl sulphoxide as cryoprotective agent and stored in liquid nitrogen. For reconstitution of frozen cells we found that the use of dextran II0 inhibited leucoagglutination. The viability and function of the reconstituted leucocytes were assessed by their morphological appearance, their capacity to phagocytose and kill Candida albicans organisms, their ability to reduce the dye nitroblue tetrazolium (NBT) in vitro and to incorporate tritiated thymidine into DNA and by the growth of colony forming units (CFUc) in agar culture. With this method of cryopreservation the phagocytic function of mature neutrophils is retained to some extent but their capacity to reduce NBT and their microbicidal activity are completely lost. In contrast CFUc may remain after storage for periods of at least 2 years.
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PMID:The cryopreservation of leukaemia cells: morphological and functional changes. 106 49

Two culture methods are available for the study of the blast cells of acute myeloblastic leukemia (AML); first, a minority of blast cells will form colonies in methylcellulose cultures in the presence of suitable growth factors. Second, clonogenic blast cells will increase in suspension cultures. Both methods can be used to assess the sensitivity of blasts to chemotherapeutic drugs, but different dose-response curves are obtained with each. Thus cytosine arabinoside (ara-C) is more toxic to clonogenic blasts in suspension than in methylcellulose, while for 5-azacytidine (5-aza) the reverse is seen. Arabinofuranosyl-5-Azacytosine (ara-AC) combines the chemical features of the two drugs. That is, its sugar moiety has the same diastereomeric change in the furanose ring as ara-C and its pyrimidine ring has the same substitution of nitrogen for carbon at the 5' position as 5-aza. We compared the sensitivity of AML blasts with ara-Ac in suspension and in methylcellulose. As a control, the same comparison was made for the sensitivities to ara-C. Blast cells were less sensitive to ara-AC than to ara-C under all conditions; but, ara-AC sensitivity was greater for cells in methylcellulose than for cells in suspension. Thus, AML blasts respond to ara-AC in culture with a pattern similar to that of 5-aza and opposite to that of ara-C. Since ara-C is a more useful drug in the treatment of AML than 5-aza, we interpret the culture results as predicting that ara-AC may not be effective in AML.
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PMID:A comparison of the lethal effects in culture of cytosine arabinoside and arabinofuranosyl-5-azacytosine acting on the blast cells fo acute myeloblastic leukemia. 138 80

Between 1978 and 1988, 20 children with medulloblastoma (MB) of the brain were treated postoperatively with MOPP (nitrogen mustard, vincristine, prednisone, and procarbazine). All but one received post-operative radiation prior to MOPP. Eight of 20 patients remained in continuous complete remission from MB, two of whom eventually developed myelodysplastic syndrome (MDS). Following resection of MB at age 12 months, one patient was treated with 24 courses of MOPP over 2 years without radiation therapy. She developed pancytopenia, and MDS was diagnosed 19 months after the completion of MOPP. Analysis of unstimulated bone marrow (BM) chromosomes showed structural abnormalities involving chromosomes 7, 10, 17, and 21. Eight months later, MDS evolved into acute myeloid leukemia. The second patient was diagnosed with MB at age 7 years and received postoperative craniospinal radiation followed by 12 courses of MOPP over one year. Five months after completion of MOPP, she developed MDS with monosomy 7 on chromosome analysis of bone marrow cells. Therapy-related MDS may be a complication of MOPP chemotherapy for MB in young children.
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PMID:Therapy-related myelodysplastic syndrome in children with medulloblastoma following MOPP chemotherapy. 146 65

Autologous transplantation of hematopoietic stem cells (HSC) is an alternative therapeutic for patients with malignant hemopathies (acute leukemia, lymphoma...) especially when no HLA-identical sibling donor is available. Hsc harvesting (marrow or peripheral blood) is performed during complete remission and is cryo-preserved in liquid nitrogen. The HSC graft, infused after treatment intensification, results in a rapidly occurring hematopoietic reconstitution. As the graft is potentially contaminated by residual malignant cells, an ex-vivo treatment by chemical or immunological treatment can contribute to a reduction and maybe even a disappearance of the malignant population. The encouraging results seen after presently autologous transplantation concerns unfortunately only selected groups of patients (acute myeloid leukemia in particular). Progress in biotechnologies (hematopoietic growth factors, monoclonal antibodies, interleukin-2) now allow us to consider new therapeutic strategies and should contribute to improved clinical results after autologous transplantation.
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PMID:[Autologous graft of hematopoietic stem cells. Current and perspective strategies]. 168 22

The application of autologous bone marrow transplantation (ABMT) in treating acute leukemias in children has been limited by the presence of residual occult viable leukemic cells in the marrow cell suspension. One approach to this problem is the ex vivo treatment ("purging") of the autograft to eradicate these tumor cells yet spare the normal lymphohematopoietic stem cells. Initial studies of acute myeloid leukemia (AML) in a rodent model demonstrated that incubation with 4-hydroperoxycyclophosphamide (4HC), a congener of cyclophosphamide and an active alkylating agent in aqueous solution, could effectively eliminate viable AML cells from marrow cell suspensions without apparent toxicity to normal stem cells. We have conducted clinical trials of ABMT with 4HC-treated marrow in children with acute leukemia in remission; marrow was collected, treated ex vivo with 4HC (100 micrograms/ml), and cryopreserved in liquid nitrogen until reinfusion. Children received pre-ABMT conditioning with either high-dose cyclophosphamide and total body irradiation (CY-TBI) for acute lymphocytic leukemia (ALL) or high-dose busulfan and cyclophosphamide (BU-CY) for AML. Of nine children who underwent ABMT with 4HC-treated marrow for ALL in second complete remission (CR2), all relapsed (eight in the marrow, one in the central nervous system) at a median of 5 months (range, 2-17) after ABMT and all have died with relapsed ALL or as a consequence of its treatment. Twenty-nine children with AML (five in CR1, 24 in CR2) received autografts with chemopurged marrow at a median remission duration of 3 months (range, 2-15). Three patients died from sepsis during aplasia; 10 children (one in CR1 and nine in CR2) relapsed with AML at a median of 7 months (range, 2-23) after ABMT, for an actuarial relapse rate of 47%. Sixteen patients with AML (four in CR1, 12 in CR2) are in unmaintained remission at a median of 16 months (range, 6-102) after ABMT, for an actuarial disease-free survival of 49%. Although ABMT with 4HC-treated marrow appears to have a limited role in the treatment of children with ALL who lack a suitable related donor, the results in AML are encouraging and compare favorably with both syngeneic and allogeneic BMT in similar groups of patients.
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PMID:Ex vivo chemopurging of autologous bone marrow with 4-hydroperoxycyclophosphamide to eliminate occult leukemic cells. Laboratory and clinical observations. 224 Apr 70


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