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)

The growth inhibitory effect of tumour promoters on human leukaemia and lung cancer cell lines was examined using the [3-(4,5 dimethylthiazol)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. The four cell lines used were the K562 human leukaemia cell line, its adriamycin (ADM)-resistant subline (K562/ADM), which shows the mdr phenotype, PC-9 (a human lung adenocarcinoma cell line) and its cisplatin (CDDP)-resistant subline (PC-9/CDDP), which does not show the mdr phenotype. Phorbol 12-tetradecanoate-13-acetate (TPA) and the TPA-type tumour promoters, aplysiatoxin and debromoaplysiatoxin, inhibited the growth of the two parental cell lines, K562 and PC-9. The non-TPA-type tumour promoter, okadaic acid, also inhibited the growth of the two parental cell lines in a dose-dependent manner. TPA-type and okadaic acid inhibited the growth of K562/ADM more weakly than that of K562, and showed no growth inhibition in PC-9/CDDP. Anhydrodebromoaplysiatoxin, an inactive derivative of the TPA-type tumour promoter, could suppress the growth of K562 and K562/ADM only at high concentration (more than 50 pM) and it showed similar growth inhibitory effects on the two cell lines. Okadaic acid tetramethyl ether, the inactive form of the non-TPA-type tumour promoter did not inhibit the growth of any of the cell lines. The growth inhibitory effect of these compounds was well correlated with their tumour-promoting activity. A study of the accumulation of okadaic acid revealed that the amount of 3H-okadaic acid in K562/ADM and PC-9/CDDP was similar to that in their parental cells indicating that cross-resistance to this tumour promoter in the drug-resistant cell lines is not due to a difference in the amount of drug accumulated in sensitive and resistant cells. These results suggest the presence of another common mechanism for resistance to ADM and CDDP as well as to TPA- or non-TPA-type tumour promoters.
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PMID:Cross-resistance to tumour promoters in human cancer cell lines resistant to adriamycin or cisplatin. 220 49

We report here a patient who was diagnosed as having acute lymphoblastic leukemia (ALL-L2) and colon carcinoma simultaneously and a successful operation for the colon carcinoma was performed preceded to the treatment of ALL. The patient was a 43-year-old male who presented with acute abdominal symptoms and was diagnosed as ALL by the hematological examination and as colon carcinoma (well differentiated adenocarcinoma, Borrmann II) by colon fiberscope. The patient was underwent sigmoidcolectomy for colon carcinoma and was received antibiotics as well as recombinant human granulocyte colony-stimulating factor (rhG-CSF), Approximately two weeks later, the patient received AdVP (Adriamycin, vincristine, and prednisolone) for ALL and achieved a complete remission. It might be possible for some leukemia patients manifesting acute abdominal symptoms to perform surgical approaches, since the prognosis of leukemia patients improved and supportive therapies, including an application of rh-CSF, have developed.
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PMID:[Successful induction chemotherapy after colectomy in a case of acute lymphoblastic leukemia associated with obstructive ileus caused by sigmoid colon carcinoma]. 232 88

Conditioned media (CM) from a human lung adenocarcinoma cell line expressing interleukins 1 and 6 (IL-1, IL-6), granulocyte (G), macrophage (M), and GM colony-stimulating factors (G, M, GM-CSF) and transforming growth factor beta (TGF beta) were used to stimulate growth of bone marrow (BM) cells from 18 persons with leukemia, myelodysplastic syndrome, or lymphoma. The objective was to increase numbers of analyzable metaphases and to enhance the likelihood of detecting cytogenetic abnormalities. Although more mitotic cells were observed with CM, the detection rate of cytogenetic abnormalities decreased in 12 of 18 cases. These data indicate that use of CM for cytogenetic analyses may favor growth of normal versus leukemia cells and mask cytogenetic abnormalities.
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PMID:Use of conditioned media in cell culture can mask cytogenetic abnormalities in acute leukemia. 233 74

We studied the antitumor activity of newly synthesized bis(1-acyloxymethyl) derivatives of 4,4'-(1,2-ethanediyl)bis(2,6-piperazinedione) using i.p.-i.p. models of P388 leukemia and B16 myeloma. As a result, we found 4,4'-(1,2-ethanediyl)bis(1-isobutoxycarbonyloxymethyl-2,6-piperazi nedione) (MST-16) to possess considerable therapeutic activity. MST-16 showed not only marked life-prolonging effects in both P388 leukemia- and B16 melanoma-bearing mice but also a greater therapeutic ratio than did its parent compounds, ICRF-154 and ICRF-159. Further studies revealed that MST-16 has considerable therapeutic activity against a number of other tumors such as ascitic forms of L1210 leukemia, colon 26 adenocarcinoma, and MH-134 hepatoma and solid forms of B16 melanoma, Lewis lung carcinoma, colon 38 adenocarcinoma, and M5076 fibrosarcoma. These results suggest that MST-16 is very promising as an antitumor agent.
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PMID:Antitumor activity of MST-16, a novel derivative of bis(2,6-dioxopiperazine), in murine tumor models. 235 66

Three cases of pulmonary atypical mycobacteriosis (AM) were reported. Two cases were associated with lung cancer in which the diagnosis of malignancy was difficult and delayed by the coexistence of AM. The third was a case of adult T-cell leukemia (ATL) which manifested during the course of AM. In case 1 (73 years, male) and case 2 (86 years, male), chest roentgenogram abnormalities as well as clinical symptoms were considered to be caused by mycobacteriosis because of positive smear of acid-fast bacilli in sputa on admission. Therefore it took four months and three months respectively for final diagnosis of lung cancer. The autopsy of case 1 revealed a poorly differentiated adenocarcinoma with coexisting foci of squamous cell carcinoma in right lower lung, and granulomatous inflammations with caseating necroses in right mid and lower lungs. M. avium complex was cultured from sputum on admission, and also a high titer of HTLV-I antibody was demonstrated. In case 2 malignant cells were detected in sputa (class V), however his general condition did not allow an aggressive anticancer chemotherapy and he died of malignancy with complication of thromboangiitis obliterans on right lower leg. Case 3 was a 76-year-old male who had been diagnosed as lung AM for more than two years. His chest radiography showed bilateral infiltrative shadows with frequent positive cultures of M. avium complex (more than 100 colonies) from sputum. A generalized lymphadenopathy including right hilar lymph node on chest X-ray film was followed by the presence of atypical lymphocytes in peripheral blood and the elevation of HTLV-I antibody in serum. Four months later he died with hypercalcemia and renal failure in spite of chemotherapy (CPM + VCR + ADR + PLS). The above cases suggest that AM as well as tuberculosis should be considered when pulmonary infiltrates were observed in malignant patients, especially in patients with retrovirus infections.
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PMID:[Three cases of pulmonary atypical mycobacteriosis associated with lung cancer and adult T-cell leukemia]. 237 33

A series of 2-aminoalkyl-5-nitropyrazolo[3,4,5-kl]acridines (pyrazoloacridines) was evaluated in vitro for activity against a panel of human tumor cell lines of breast, colon, or lung origin. Several pyrazoloacridines were found to possess solid tumor selectivity relative to their activity against murine leukemia L1210 cells as well as human lymphoblastoid cells. The superior compounds in this regard were also found to exhibit excellent activity against primary human tumors in stem cell clonogenic assays. In addition, many of the compounds tested were found to be selectively cytotoxic to hypoxic relative to oxic HCT-8 colon adenocarcinoma cells, a property that may be a consequence of the potentially reducible 5-nitro function. A number of pyrazoloacridines were also found to exhibit potency against noncycling Chinese hamster ovary cells comparable to that observed against actively dividing cultures. Consistent with their favorable activity against nondividing cells, further testing of the pyrazoloacridines revealed that generally less drug is required to inhibit RNA synthesis than DNA synthesis in L1210 cells. Collectively these data indicate that the pyrazoloacridines represent a novel class of antitumor agents which warrant further preclinical evaluation for their potential clinical usefulness in the treatment of solid tumors.
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PMID:Pyrazoloacridines, a new class of anticancer agents with selectivity against solid tumors in vitro. 244 May 64

Aclacinomycin is a member of naturally occurring anthracyclines having three sugar moieties in the molecule. It showed antitumour activity on various mouse and rat tumours. Combination therapy with AraC etc. gave remarkable clinical results on acute myeloid leukaemia. Aclacinomycin strongly inhibits RNA synthesis of the tumour cells. It has lower cardiac toxicity than adriamycin and no mutagenicity. THP-Adriamycin is a derivative of adriamycin designed from the structure of baumycins. It showed stronger effects than adriamycin in inhibiting many mouse tumours such as L1210 and P388 leukaemia, B16 melanoma and colon 38 adenocarcinoma. THP-Adriamycin is rapidly taken up by both adriamycin-sensitive and resistant leukaemic cells. Its level of cardiac toxicity is as low as that of aclacinomycin. Ditrisarubicins are new naturally occurring anthracyclines isolated from Streptomyces having six sugar moieties in the molecule. Ditrisarubicin has a potent cytostatic and antitumour activities on adriamycin resistant mouse leukaemia. Its binding constant to DNA is extremely high compared with other anthracyclines.
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PMID:Experimental studies of new anthracyclines: aclacinomycin, THP-adriamycin and ditrisarubicins. 244 79

Chromophore modification of the anthracenediones related to mitoxantrone in an attempt to provide agents with diminished or no cardiotoxicity has resulted in a novel class of DNA binders, the anthrapyrazoles. Selected biochemistry, electrochemistry and tumour biology were carried out for a series of compounds possessing the same upper and lower side chains but with varying A-ring hydroxylation patterns. The anthrapyrazoles bind strongly to DNA, are selective and potent inhibitors of DNA synthesis and cause the formation of single-strand breaks in DNA. They also induced far less (20-200-fold) superoxide dismutase-sensitive oxygen consumption than doxorubicin in the rat liver microsomal system, a property that may be indicative of reduced cardiotoxicity. This result is in accord with their polarographic properties in which the anthrapyrazoles show a much greater resistance to reduction (E'1/2 = -0.983- -1.085 V) relative to daunorubicin (E'1/2 = -0.625 V) and mitoxantrone (E'1/2 = -0.775 V). The anthrapyrazoles demonstrate high levels of activity against a broad range of murine tumours in vivo including the P388 leukaemia and mammary adenocarcinoma 16c lines detailed in this study.
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PMID:Design, biochemical pharmacology, electrochemistry and tumour biology of anti-tumour anthrapyrazoles. 245 96

N-Propyl-N-nitrosourea is a strong leukemogen that induces myelogenic leukemia in Donryu rats and thymic lymphoma in F344 rats when administered in drinking water. In the present study, a single or multiple doses of PNU (total 500 mg/kg body weight) was given to young male and female F344 rats via a stomach tube. The results demonstrated that the percentage of tumor-bearing rats was 100% in all PNU-treated male groups, while that of the control group was 46%. Predominant tumors induced by PNU in male rats were lung adenoma/adenocarcinoma followed by peritoneal mesothelioma, and forestomach papilloma. In females, the tumor incidence of PNU-treated groups varied between 58% and 92% while that of the control group was 42%. Although pituitary tumor was the most frequent tumor in PNU-treated female rats, it was thought to be spontaneous since its incidence in each experimental group was not statistically different from that of the control group. Lung tumors and forestomach papillomas were also induced by PNU in female rats. No thymic lymphoma, however, was found in any of the PNU-treated groups of either sex. Lung tumors developed in almost all PNU-treated male rats and in about one-third of PNU-treated female rats. Mesothelioma was induced only in male rats, and its incidence depended on the treatment schedule. Induced mesotheliomas were extensively examined histologically, histochemically, immunohistochemically, and electron microscopically.
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PMID:Induction of lung tumors and peritoneal mesotheliomas in F344 rats given intragastric N-propyl-N-nitrosourea and histochemical, immunohistochemical, and ultrastructural characteristics of induced mesotheliomas. 245 26

The Boon-Leigh procedure, involving condensation of a 6-chloro-5-nitropyrimidine (22) with an alpha-amino ketone (20 or 21) followed by reduction of the nitro group, cyclization, and L-glutamylation, led to the formation of 11-deazahomofolate (29) and its 10-methyl derivative (30). The corresponding (6R,S)-5,6,7,8-tetrahydro (4, 5) and 7,8-dihydro (31, 32) derivatives were prepared by catalytic hydrogenation. (6S)-11-Deazatetrahydrohomofolate was prepared from 29 by enzymatic reduction. Compounds 29 and 30 had little effect (IC50 greater than 2 x 10(-5) M) on Lactobacillus casei glycinamide ribonucleotide (GAR) formyltransferase but (6R,S)-11-deazatetrahydrohomofolate (4) is a potent inhibitor of this enzyme (IC50 = 5 x 10(-8) M). It is at least 100 times more inhibitory than 33, the 6S compound, indicating that the 6R component of the mixture having the unnatural configuration at C6 (34) is responsible for the potent inhibition. Compound 4 is a much weaker inhibitor of murine (L1210) and human (MOLT-4) leukemia cell GAR formyltransferases (IC50 greater than 1 x 10(-5) M). (6R,S)-11-Deaza-10-methyltetrahydrohomofolate (5) (IC50 = 1.1 x 10(-5) is 200 times weaker than 4 against L. casei GAR formyltransferase. However, 11-deaza-10-methyldihydrohomofolate (32) is more inhibitory (IC50 = 5.5 x 10(-7) M) than 5 or 30. None of the compounds showed inhibition of L. casei aminoimidazolecarboxamide ribonucleotide (AICAR) formyltransferase, dihydrofolate reductase, or thymidylate synthase. The dihydro derivatives 31 and 32 are 5% as active as dihydrofolate as substrates for L. casei dihydrofolate reductase. Compound 4 showed moderate inhibition of the growth of L. casei, Streptococcus faecium, MOLT-4 cells, and MCF-7 human breast adenocarcinoma cells.
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PMID:Folate analogues. 31. Synthesis of the reduced derivatives of 11-deazahomofolic acid, 10-methyl-11-deazahomofolic acid, and their evaluation as inhibitors of glycinamide ribonucleotide formyltransferase. 249 18


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