Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell survival in response to doxorubicin (Dx) and cis-diammine-dichloroplatinum (cis-Pt) administration, either alone or combined with hyperthermic treatment, was analyzed in human osteosarcoma (U-2-OS), murine melanoma (B16V) and murine leukemia (P388) cell lines and in Dx-resistant sublines derived from B16V and P388. In all cell lines tested there was an enhancement of drug toxicity by hyperthermia. In U-2-OS, the increase was more pronounced for cis-Pt than for Dx. In B16V and in P388, the increase in Dx toxicity was of the same degree in Dx-sensitive and Dx-resistant sublines, whereas heat-induced sensitization to cis-Pt was higher in Dx-resistant sublines than in their Dx-sensitive counterpart. Analysis of the protein pattern in the various cell lines showed that the synthesis of heat-shock proteins induced by heat was not influenced by the combined use of drugs and heat. Moreover, in spite of some differences in the overall protein pattern, no significant differences in the basal levels of heat-shock protein synthesis or in the extent of its induction after heat shock were observed between murine cell lines relatively sensitive to Dx and their corresponding selected resistant cells.
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PMID:Interaction of heat with chemotherapy in vitro: effect on cell viability and protein synthesis in human and murine cell lines. 347 10

Body weight and lean body mass are different reflections of the nutritional status of patients receiving cancer chemotherapy. In the present study, the relation between lean body mass and body weight during cytostatic treatment was investigated in 3 groups of newly-diagnosed children and young adults with acute lymphocytic leukemia, osteosarcoma, or a small round cell sarcoma. Body weight and lean body mass were determined before and after an initial period of cytostatic treatment. Lean body mass was derived from total body water volume, which was assessed by deuterium oxide dilution. A significant dissociation between body weight and lean body mass was observed in leukemia patients (n = 8, P = 0.008, paired t-test), and in osteosarcoma patients (n = 13, P = 0.001). No dissociation was found in patients with a small round cell sarcoma (n = 8, P = 0.839). We conclude that during cancer chemotherapy periodic assessment of body weight may give a false picture of the preservation of lean body mass. Considering the course of body weight alone may prevent the establishment of a timely diagnosis of malnutrition, which is mandatory for optimal supportive care.
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PMID:Dissociation of body weight and lean body mass during cancer chemotherapy. 347 60

One hundred and sixty one children who have developed more than one primary neoplasm have been identified. Children with tumours of the central nervous system, retinoblastoma and leukaemia were those most frequently observed to develop a second malignancy whilst osteosarcoma was the most common second tumour. The patterns of second neoplasms appear to be changing and a recent increase in the number of children with leukaemia and lymphoma who develop second primary tumours has been observed. In this series, the two most frequent associations of tumours were retinoblastoma followed by osteosarcoma and the combination of acute leukaemia with a tumour of the central nervous system. Genetic factors which may have contributed to the development of the second primary tumour were identified in 53 patients (33%), 33 of whom had the genetic form of retinoblastoma. In an analysis of the treatment of 151 patients, for whom the interval between the two neoplasms was greater than 12 months, the second malignancy was considered to be 'radiation associated' in 93 (61%). Fifty children (33%) had been treated with either single or multiple agent chemotherapy which included an alkylating agent in 38. Forty five children had received a combination of chemotherapy and radiotherapy and of these, 10 developed leukaemia as their second tumour. Of the 19 secondary leukaemias, 16 have occurred in patients treated since 1970.
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PMID:Patterns of multiple primary tumours in patients treated for cancer during childhood. 347 72

Twenty patients with osteosarcoma and pathologic fractures were treated with a chemotherapeutic regimen consisting of cis-diamminedichloroplatinum-II (CDP), Adriamycin (ADR) (doxorubicin) and high-dose methotrexate with citrovorum factor "rescue" (MTX-CF). Before the introduction of the regimen, the primary tumor in two patients was treated by immediate amputation and in 13 with preoperative intra-arterial CDP. Among these 13 patients, responses (healing) were observed in 11 (one required the addition of radiation therapy). In three patients, the responses were so dramatic that, at their request, surgery was deferred and treatment exclusively with chemotherapy was instituted. Based on this experience, treatment exclusively with chemotherapy was also administered to an additional five patients who were admitted without pathologic fractures. In the course of such treatment, pathologic fractures also developed; notwithstanding, chemotherapy was maintained and healing also occurred. One of the 20 patients had pulmonary metastases at diagnosis; these were resected after treatment and pathologic examination revealed no evidence of viable tumor. The remaining 19 patients were free of pulmonary metastases but these later developed in seven patients. These data were compared to a historical control series in which 16 of 21 patients with pathologic fractures developed pulmonary metastases. Three of the chemotherapy treated patients died of nonosteosarcoma related causes (leukemia, generalized varicella, and a metabolic complication). Overall, survival was improved in the chemotherapy treated patients as compared to the historical control series: 10 of 20 versus 6 of 21, respectively. Pathologic fractures in osteosarcoma may heal under treatment with chemotherapy, which also has a favorable impact on the eradication of pulmonary metastases and survival.
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PMID:Pathologic fracture in osteosarcoma. Impact of chemotherapy on primary tumor and survival. 349 61

Gallium nitrate is the anhydrate salt of the naturally occurring heavy metal. It has demonstrated antitumor activity in a variety of murine tumor models, including Walker carcinosarcoma 256, fibrosarcoma M-89, leukemia K-1964, adenocarcinoma 755, mammary carcinoma YMC, reticulum cell sarcoma A-RCS, lymphoma P1798, and osteosarcoma 124F. Preclinical studies performed in rats, rabbits, dogs, and monkeys showed the dose-limiting toxicity to be renal. The hepatic, pulmonary, gastrointestinal, hematologic, and integumentary systems were also involved. The major route of elimination is the kidneys, with 35%-71% of the infused dose excreted within 24 hours. Three phase I studies suggested the following phase II doses: 700-750 mg/m2 by short infusion, once every 2-3 weeks; 300 mg/m2/day by short infusion for 3 consecutive days, to be repeated every 2 weeks; and 300 mg/m2/day by continuous infusion for 7 consecutive days, to be repeated every 3-5 weeks. The major organ toxicity reported was renal; however, this can be adequately controlled either by hydration and osmotic diuresis or by use of continuous schedule. (Either maneuver appears to allow delivery of the recommended phase II dose with a less than 30% risk of change in serum creatinine.) In limited phase II evaluation, the drug has shown antitumor activity in patients with either refractory lymphomas or small cell lung carcinoma, with total objective response rates of 28% and 11%, respectively. In addition, it has been effective in the treatment of patients with cancer-related hypercalcemia by having an inhibitory effect on calcium reabsorption from bone. Single-agent phase II studies are planned in all major tumor types. Some are already ongoing in patients with genitourinary malignancies (renal, bladder, prostate, testicular), small cell lung carcinoma, and multiple myeloma. Metabolic studies are in progress at Memorial Sloan-Kettering Cancer Center to further elucidate the mechanism or mechanisms of the hypocalcemic effects.
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PMID:Gallium nitrate: the second metal with clinical activity. 353 51

Studies of the presenting height of children with malignancies have produced conflicting results, from an excess of taller patients to an excess of shorter patients. The problems of measurement bias, inadequate comparison populations, small numbers of patients, subgroup analyses, and overreliance on simple significance tests are all possible reasons for the variation in results. To clarify this issue, we studied heights at diagnosis of 3657 children and adolescents aged under 18 years. Their malignancies included acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin's disease, acute non-lymphoblastic leukaemia, osteosarcoma, retinoblastoma, neuroblastoma, Wilms' tumour, rhabdomyosarcoma, and Ewing's sarcoma. Compared with published standards for the heights of children in control populations, no significant deviation from population norms was found for patients in any of the 10 disease categories after proper adjustment for multiple significance testing.
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PMID:Height at diagnosis of malignancies. 360 84

A multicentre registry of children who had been successfully removed from therapy for some common childhood cancers (Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, nephroblastoma, acute lymphatic leukaemia and other leukaemias) was established in Italy in 1981. The present study describes mortality and occurrence of second primary malignancies (SPMs) among 1467 children who were alive when the registry was established. Follow-up ended on December 31, 1983 for mortality and 1 year later for the occurrence of SPMs. Sixty-seven deaths were recorded, 11 of which were due to causes other than progression of the original disease. Eleven incident SPMs were identified (i.e. 3 acute myeloid leukaemias, 3 thyroid carcinomas, 1 bilateral breast carcinoma, 1 liver malignant mesenchymoma, 1 astrocytoma, 1 chondrosarcoma and 1 osteosarcoma) corresponding to an incidence rate of 2.1/1000 patient-years at risk. Anecdotal reports were collected regarding 2 further SPMs (a thyroid carcinoma and a myeloid leukaemia) as well as several benign tumours, including 2 mammary fibroadenomas.
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PMID:Late deaths and second primary malignancies among long-term survivors of childhood cancer: an Italian multicentre study. 365 74

Against the background of a seemingly short latency period for the majority of childhood tumors and the theory of the existence of a prezygotic variation of the two-step mutation model prior to tumor development, the risk of second cancer after cancer in childhood is examined in the population of Denmark from 1943-1980. A total of 5319 cases of primary cancer in childhood were followed until patient death or the end of 1980, and the number of secondary tumors were observed, specifying on diagnosis, age, sex, and time since first tumor diagnosis. A total of 23 secondary tumors was observed (O) against an expected (E) figure of 6.5, corresponding to an O/E ratio of 4.4. The risk varies greatly according to time elapsed since first diagnosis, with the highest risk in close relation to the primary tumor. The second tumor is probably more frequently localized to the skin and brain than elsewhere, and the risk of a second tumor is particularly associated with leukemia and osteosarcoma in childhood. It is concluded that the results are compatible with the theory of a prezygotic variation of the two-step mutation model.
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PMID:Risk of second cancer after cancer in childhood. 369 26

Sixty-six cases of multiple primary neoplasms in children in Japan were collected, including 8 cases of our own. These could be divided into 19 synchronous and 47 metachronous multiple neoplasms. Metachronous or multiple primary neoplasms comprised leukemia, osteosarcoma, mesenchymal sarcoma, epithelial carcinoma and others in contrast to synchronous neoplasms which consisted of many pairs of embryonic tumors. The presumptive factors for multiple primary neoplasms suggested radiotherapy-associated cancers in 30%, radiochemotherapy-associated in 13%, chemotherapy-associated in 34%, and genetic factor-related in 36% of cases. Chromosomal analysis was performed in 12 cases. Three of 4 leukemias revealed major karyotypic abnormalities in the leukemic cells. No 13q14, deletion was detected in 5 cases with multiple primary neoplasms developed with retinoblastoma. Frequent incidence of sister chromatid exchange (SCE) was detected in cultured fibroblasts or lymphocytes from one of 3 cases of second primary neoplasms associated with chemotherapy. The time interval between both neoplasms ranged from 2 to 15 years in the majority of cases. Chemotherapy-associated multiple primary neoplasms seemed to appear more quickly than radiotherapy-associated multiple primary neoplasms. Seven children out of 459 long-term survivors of childhood cancer developed multiple primary neoplasms during the period from 5 to 20 years after diagnosis of the first tumor at the National Cancer Center Hospital, Tokyo. The relative risk was suggested to be 14 times higher than the expected incidence of childhood cancer in Japan. Refinement of treatment, long-term monitoring and protective procedures for high-risk patients against multiple primary neoplasms are therefore warranted.
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PMID:[Second malignant neoplasms in childhood]. 372 68

The folate analogue 5,8-dideazaisopteroylglutamate (IAHQ; NSC-289517) inhibits the growth of a variety of human tumor cells in vitro such as colon, breast and osteosarcoma. Since IAHQ has only modest activity against L1210 leukemia in mice, it was tested in combination with methotrexate (MTX), probenecid, or verapamil in an effort to enhance efficacy. Single drug or drug combinations were administered every other day 3 or 5 times beginning on day 1 following the administration of 10(6) L1210 cells per animal. The combination of IAHQ (100 mg/kg) plus MTX (10 mg/kg) produced a decrease in mean survival time compared to that of MTX alone, regardless of whether the drugs were initiated on the same day or whether either one was started 2 days prior to the other. IAHQ (150 mg/kg) plus verapamil (5, 10, or 20 mg/kg) did not alter significantly the results produced by IAHQ alone. However, the combination of IAHQ (150 mg/kg) plus probenecid (250 mg/kg) augmented the increase in mean survival time above that produced by IAHQ alone by 82% (p = less than 0.001). The results suggest that probenecid could be used to enhance the effectiveness of IAHQ against solid tumors such as colon adenocarcinoma.
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PMID:Effects of 5,8-dideazaisopteroylglutamate (IAHQ) on L1210 leukemia in mice when given alone and in combination with methotrexate, probenecid, or verapamil. 380 78


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