Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although cellular drug resistance is considered to be an important cause of the poor prognosis of children with relapsed acute lymphoblastic leukaemia (ALL), the knowledge of drug resistance in these patients is very limited. Different aspects of drug resistance were studied in 17 children with relapsed ALL. The in vitro sensitivity profile was determined using the MTT assay. Cells from relapsed children were significantly more resistant to 6-thioguanine, prednisolone, cytosine arabinoside, daunorubicin (DNR), mustine-HCl and mafosfamide but not to L-asparaginase and vincristine (VCR) than cells from 41 children with ALL at initial diagnosis. Some relapsed patients showed a general drug resistance while others were resistant to only 1-3 drugs. The relevance of the multidrug resistance (MDR) model was analysed: In all DNR- and VCR resistant cases a co-resistance to drugs not involved in the MDR model was found. P-glycoprotein was not detected in any of 28 untreated and 14 relapsed samples tested. VCR- and DNR accumulation in the most resistant cells were not lower than in sensitive cells. Resistance modifiers did not potentiate the cytotoxicity of VCR and DNR. We conclude that resistance to anthracyclines and vinca alkaloids in childhood relapsed ALL is not due to P-glycoprotein mediated MDR. Different types of drug resistance varying from a resistance to only one drug to a general chemoresistance, can be detected in children with relapsed ALL. VCR and L-asparaginase seemed to be only infrequently involved in drug resistance. Knowledge of drug resistance might lead to more effective and less toxic therapies for children with relapsed ALL.
Br J Cancer 1992 May
PMID:Different types of non-P-glycoprotein mediated multiple drug resistance in children with relapsed acute lymphoblastic leukaemia. 135 Feb 7

The effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer was investigated in rats using magnetic resonance imaging. Experimental liver metastatic tumors were established in syngeneic BDIX rats after intrasplenic injection of DHD/K12 colon adenocarcinoma cells. Each rat with implanted liver tumors received s.c. injections of somatostatin analogue RC-160 (50 micrograms/kg) or the vehicle (control) twice a day for 4 weeks, starting 3 weeks after tumor inoculation. During the treatment with RC-160, the growth of liver tumors was studied quantitatively by measuring liver tumor volumes in vivo with magnetic resonance imaging at intervals of 7 days. Chronic administration of RC-160 inhibited the growth of hepatic metastases of colon cancer in rats. Significant inhibition of liver tumor growth in RC-160-treated rats was observed throughout the treatment. The final liver tumor volume in the treated rats was decreased by 56.1% as compared to the controls. The treatment with RC-160 reduced the percentage increase in liver tumor volume from 1575 +/- 674% (mean +/- SEM) for the control to 1034 +/- 727% in the treated group. The tumor volume doubling time in treated rats was 3.7 days longer than the controls. The liver tumor growth delay time was 15.1 days. At the end of the treatment, the incidence of ascites and the weights of tumorous livers were also decreased by RC-160 treatment. Administration of RC-160 prolonged the median survival time by 13 days in treated rats. In cell cultures, significant inhibitory effects of somatostatin-14 and RC-160 on the growth of DHD/K12 colon cancer cells were determined by MTT assay and [3H]-thymidine incorporation assay, indicating direct effects of these peptides on the growth of colon cancer cells in vitro. These data suggest that administration of RC-160 could inhibit the growth of colon cancer and their hepatic metastases in rats. Somatostatin analogue RC-160 might be considered as a potential new agent for the treatment of patients with hepatic metastases of colorectal cancers.
Cancer Res 1992 Nov 01
PMID:Inhibitory effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer in rats: a study with magnetic resonance imaging. 135 23

The MTT cell viability assay is widely used in determining drug sensitivity profiles for patients with hematological malignancies and in primary screening of potential chemotherapeutic drugs. Because the multidrug resistance (MDR) phenotype is associated with these malignancies, and since many vital dyes are effluxed from MDR expressing cells, we have investigated whether the MDR phenotype interferes with the MTT assay. In CCRF-CEM and K562 human leukemic cell lines and drug-resistant sub-lines developed from them, comparison of the MTT assay with other cell viability assays showed significant variation in IC50 concentrations, although the resistance relative to the sensitive parent cell was correlated. Inclusion of verapamil, an inhibitor of drug efflux activity, had no effect on the MTT assay.
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PMID:The MTT cell viability assay for cytotoxicity testing in multidrug-resistant human leukemic cells. 136 Dec 10

The high-affinity receptor for IgG, Fc gamma RI, expressed on monocytes and interferon-gamma (IFN-gamma)-stimulated neutrophils, is a trigger molecule for cell-mediated cytotoxicity. We have prepared murine monoclonal antibodies (MoAb 22 and MoAb 32) that bind to Fc gamma RI outside the ligand binding site and thus bind to and trigger cytotoxicity that is not competed by other immunoglobulins. Because of these properties, it seemed that these MoAbs would be very useful for the development of bispecific antibodies (BsAb) for targeting normal cellular immune defense mechanisms as a new form of immunotherapy for treatment of cancer. BsAbs incorporate into a single molecule the binding specifities of two different antibodies, and, thus, can be used to target myeloid cells to tumors, ensure activation of cellular cytotoxic mechanisms, and target cell lysis and/or phagocytosis. BsAbs were prepared using anti-Fc gamma RI MoAb and an anti-myeloid cell MoAb, PM81, reactive with the CD15 antigen, for studies of antibody-dependent cellular cytotoxicity. Conjugates were made by cross-linking sulfhydryl groups of Fab fragments of MoAb 32 or 22 (both IgG1) and sulfhydryl groups added to intact PM81 (an IgM) using N-succinimdyl-acetyl-S-thioacetate (SATA). The resulting product was purified by high-performance size-exclusion chromatography. The ability of the BsAbs to mediate attachment of human monocytes to tumor target cells was confirmed in a microtiter well assay of binding of MTT-labeled U937 cells (a human Fc gamma RI-bearing cell line) to SKBR-3 (PM81-reactive breast carcinoma) target cells. The ability of the BsAbs to mediate killing of HL-60 promyelocytic leukemia cells was studied using a 6-hour Chromium-51 release assay. Effector cells were monocytes obtained by cytopheresis and cultured for 18 hours with IFN-gamma. Monocytes alone caused minimal killing (5-20%), monocytes plus BsAb caused moderate killing (20-50%), and monocytes plus BsAb plus human serum resulted in maximal killing (50-80%). Experiments were performed to test the ability of the BsAb to purge bone marrow of small numbers of leukemia cells using bone marrow mononuclear phagocytes treated for 18 hours with IFN-gamma prior to adding target cells. Without the addition of human serum as a source of complement, a 90% depletion of clonogenic HL-60 cells could be demonstrated. With human complement, up to 95% depletion was seen. Thus, this BsAb possessed the ability to lyse tumor cell targets by two different mechanisms, complement and cell-mediated lysis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Initial trial of bispecific antibody-mediated immunotherapy of CD15-bearing tumors: cytotoxicity of human tumor cells using a bispecific antibody comprised of anti-CD15 (MoAb PM81) and anti-CD64/Fc gamma RI (MoAb 32). 136 20

MCF-7 and HT-29 cell lines were selected as a reliable model to examine the possible parameters affecting the sensitivity of tumour cells to photodynamic therapy (PDT) using a dye-laser at 630 nm. The chemical composition of haematoporphyrin derivative (HPD) was determined by high-performance liquid chromatography (HPLC) analysis and was in agreement with reported values. MTT assays were performed to assess the time-dependency of PDT and the influence of the output power and light fluence. The results showed a maximal cytotoxicity 48 h after photoirradiation. The output power (1 or 2 W) did not significantly affect the cytotoxicity when the fluence was constant (20 J/cm2). However, an increase in fluence (10-40 J/cm2) led to a significant enhancement of cytotoxicity until maximal values were reached (30-40 J/cm2). A further increase in fluence (50 J/cm2) proved to induce a fall-off in cytotoxicity related to the intense photobleaching of HPD.
Eur J Cancer 1992
PMID:MTT assays allow quick and reliable measurement of the response of human tumour cells to photodynamic therapy. 138 43

Activated by interferon gamma (IFN gamma)(50 U/ml) and lipopolysaccharide (50 ng/ml), mouse peritoneal macrophages were cocultured with the L1210 parental cell line (L1210/PRT) and its Adriamycin-, cisplatin-resistant cell lines (L1210/ADM, L1210/CDDP) for 24 h at effector: target (E:T) ratios of 10:1, 5:1 and 2:1. The direct 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT)-cleavage assay, a new improved indirect MTT assay, and the colony-formation assay were used to quantify macrophage-mediated suppression of these non-adherent tumour targets. The results showed that the macrophages can produce formazan at a high level, which can interfere with the final results of a direct MTT assay. The new indirect MTT assay can avoid such interference because the effectors are separated from the targets before the assay is performed, so the real viability of the targets is reflected. An indirect MTT assay, as developed in this study, could be better than the direct assay for examining the suppressive effect of activated macrophages on non-adherent tumour cells in vitro. This study also revealed that all the L1210 cell lines can be suppressed significantly by the macrophages at E:T ratios of 10:1 and 5:1 while the two drug-resistant cell lines have lower survival rates at an E:T ratio of 10:1, indicating that they are more susceptible than their parental cell line.
Cancer Immunol Immunother 1992
PMID:A new 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for testing macrophage cytotoxicity to L1210 and its drug-resistant cell lines in vitro. 139 44

Conjugates of adriamycin coupled to transferrin by glutaraldehyde are cytotoxic to human promyelocytic (HL-60) and erythroleukemic (K562) cells. Growth inhibition of adriamycin-sensitive cells, as evaluated by thymidine incorporation and the MTT-assay, was higher for conjugates than for free adriamycin. The cytotoxicity toward adriamycin-resistant K562 and HL-60 cells was 3-fold and more than 10-fold higher, respectively, for the transferrin-adriamycin conjugate than for the free drug. The effect of the conjugate was dependent on its adriamycin content, i.e., on its conjugation number.
Int J Cancer 1992 Oct 21
PMID:Cytotoxicity of a transferrin-adriamycin conjugate to anthracycline-resistant cells. 139 45

A major problem associated with the chemosensitivity testing of fresh human tumour cells using the MTT assay is the contamination of nonmalignant cells in the tumour tissues. Highly purified fresh human gastric cancer cells could be obtained from 43 solid tumours and eight malignant ascites for the MTT assay. The success rate of the MTT assay was 87.9% (51 of the 58 cases), and the purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients in primary, or metastatic lesions, and also ascites. Cisplatin, mitomycin, and doxorubicin were more potent drugs than etoposide and 5-FU against gastric cancer cells. The chemosensitivity in differentiated cancer was equivalent to that in non-differentiated cancer. Twenty of the 51 patients with gastric cancer had evaluable lesions, and they received chemotherapy according to the results of the MTT assay using highly purified tumour cells. A clinical response was obtained in 12 of these 20 patients (response rate: 60.0%; five with complete response, seven with partial response).
Br J Cancer 1992 Nov
PMID:Chemosensitivity testing of fresh human gastric cancer with highly purified tumour cells using the MTT assay. 141 22

The DNA repair enzyme, O6-alkylguanine-DNA-alkyltransferase (ATase), is thought to be the principal mechanism controlling resistance to nitrosoureas and related alkylating agents. We compared the sensitivities of five human testis and five bladder tumour cell lines to two nitrosoureas (N-nitroso-N-methylurea (MNU) and mitozolomide) with cellular levels of ATase. Enzyme levels ranged from 3 to 206 fmol mg-1 protein (0.1 x 10(4) to 5.1 x 10(4) molecules/cell) in the testis lines and from 11 to 603 fmol mg-1 (0.4 x 10(4) to 9.1 x 10(4) molecules/cell) in the bladder lines. Based on IC50s in an MTT assay, the testis tumour cell lines were, on average, four times more sensitive to MNU and six times more sensitive to mitozolomide than the bladder cell lines. The cytotoxicities of MNU and mitozolomide were closely related (R = 0.9). In the testis cell lines ATase activity (molecules/cell) was related to IC50s for mitozolomide (R = 0.97) but not MNU (R = 0.78). In the bladder cell lines and overall, ATase activity correlated with cellular sensitivity to neither agent. Relatively high levels of resistance occurred in cells expressing low levels of ATase, and amongst cell lines expressing high levels of ATase, large differences in IC50s were observed. These results support the suggestion that resistance to nitrosoureas can be mediated by mechanisms other than ATase and that at relatively high levels of expression, ATase does not confer resistance in proportion to its activity.
Br J Cancer 1992 Nov
PMID:O6-alkylguanine-DNA-alkyltransferase activity and nitrosourea sensitivity in human cancer cell lines. 141 26

Recent interest in site-selective cAMP analogs has focused on the role of 8-chloro-adenosine (8-Cl-adenosine) in the inhibition of tumor cell growth by 8-chloro-cAMP (8-Cl-cAMP) (Van Lookeren Campagne, et al. Cancer Res 1991; 51: 1600-5). We have evaluated 8-Cl-cAMP and 8-Cl-adenosine for their growth inhibitory activity against two human colon adenocarcinoma cell lines, HCT116 and FET. Because these cell lines have been adapted to grow in chemically defined medium we were able to evaluate the effect of serum on 8-Cl-cAMP's growth inhibitory activity. In addition, cells grown in serum-free medium were tested for their sensitivity to 8-Cl-cAMP, serum-activated 8-Cl-cAMP and 8-Cl-adenosine. IC50 values, determined by measuring cell growth using a MTT colorimetric assay, showed that 'serum activation' of 8-Cl-cAMP was required to achieve inhibition of HCT116 (IC50 = 1.3 +/- 0.1 microM) and FET (IC50 = 2.0 +/- 0.1 microM) cell growth. IC50 values were not reached at the highest concentrations tested (IC50 > 500 microM) in the absence of serum, permitting us to conclude that 8-Cl-cAMP does not have growth inhibitory activity between 1.0 and 500 microM doses. HCT116 and FET cells grown in media containing serum and in the presence of 8-Cl-adenosine had IC50 values of 0.6 +/- 0.1 and 0.9 +/- 0.2 microM, respectively. HCT116 and FET cells grown in chemically defined medium containing 8-Cl-adenosine exhibited IC50 values of 1.0 +/- 0.1 and 3.1 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of colon tumor cell growth by 8-chloro-cAMP is dependent upon its conversion to 8-chloro-adenosine. 145 Apr 43


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