[Advanced hepatocellular carcinoma: value of systemic chemotherapy combining adriamycin, amiodarone and 5-fluorouracil].
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Adult↗
Biomedical subjects
B Chauffert
Publications and source records attributed to B Chauffert.
Histoimmunological characterization of the cellular reaction to liver metastases induced by colon cancer cells in syngeneic rats.
Artificial liver metastases were produced by injecting in vitro cultivated colonic cancer cells into the mesenteric vein of syngeneic rats. An immunohistologic study of the inflammatory host cells infiltrating the tumors was carried out from 1 to 46 days after tumor cell injection, using a set of monoclonal antibodies labelling tumor cells, macrophages or lymphoid cells subpopulations. In small metastases, 3-7 days after tumor cell injection, tumor cell foci were surrounded by a dense corona of inflammatory cells, predominantly T lymphocytes and NK cells. This inflammatory corona regressed when metastases grew larger and completely disappeared around the large metastases found more than 28 days after cell injection. Inside the metastases, the tumor cells were mixed with a small number of cells with the characteristic labelling of macrophages (KiM2R+, W3/25+); however, the inside macrophages are OX8+ in contrast to macrophages found in normal liver and in the peritumoral corona. The progressive disappearance of the coronal inflammatory cells suggests that cancer cells are able to produce or to induce other cells to produce anti-inflammatory agents inhibiting the accumulation of macrophages and lymphoid cells around the tumors.
Animals↗
Differential retention of doxorubicin in the organs of two strains of rats.
Fluorescence microscopy and high pressure liquid chromatography were used to study the decrease of doxorubicin (DXR) concentrations in the liver, spleen, heart, lung, kidney and skeletal muscle of two strains of rats at various times after a single intravenous injection of the drug (8 mg kg-1). DXR was located within the cell nucleus and was mostly undegraded, it persisted, especially in heart, lungs and spleen where it was detectable 10 days after injection. The DXR/DNA ratio, was used as an index of nuclear fixation of the drug. A major difference in the DXR/DNA ratio between the two strains were observed in heart and spleen results; the DXR/DNA ratio was significantly higher in heart and spleen compared with lung, liver and kidney in both strains.
Animals↗
Amiodarone is more efficient than verapamil in reversing resistance to anthracyclines in tumour cells.
We have previously demonstrated that amiodarone is able to reverse resistance of rat colon cancer cells to anthracyclines. We now compare the efficiency of amiodarone to verapamil one, another antiarrhythmic agent used in experimental systems and in clinical trials to enhance the effects of anthracyclines on resistant cancer cells. Amiodarone is more efficient than verapamil when both drugs are used at the same molar concentrations. Desethylamiodarone, the main metabolite of amiodarone, is as efficient as its precursor. Optimal concentrations of amiodarone are obtained without side effects in the sera of patients treated by oral administration followed by a loading infusion of amiodarone. On the other hand, maximal tolerated levels of verapamil reported in clinical trials are less efficient than amiodarone maximal levels in the reversal of resistance to anthracyclines in our experimental model in vitro. We suggest that amiodarone, which is more efficient and less toxic than verapamil, could be substituted for verapamil in future clinical trials.
Adenocarcinoma↗
Amiodarone-induced enhancement of doxorubicin and 4'-deoxydoxorubicin cytotoxicity to rat colon cancer cells in vitro and in vivo.
The mechanisms of the resistance of intestinal cancer to anthracyclines were studied on an experimental model of rat colon cancer cells. The accumulation of anthracyclines in the nucleus of living cancer cells was observed by fluorescence microscopy. This accumulation depended on both the capacity of anthracyclines to penetrate into the cell and the activity of an efflux mechanism extruding the drug from the cell. We found that 4'-deoxydoxorubicin was superior to 4 other anthracyclines in its capacity to penetrate into confluent colon cancer cells. Amiodarone, an antiarrhythmic agent used in cardiology, inhibited the efflux mechanism efficiently and increased the toxicity of anthracyclines to the colon cancer cells. Association of amiodarone and 4'-deoxydoxorubicin was able to cure 5 of 13 rats that had been inoculated i.p. previously with syngeneic colon cancer cells. This association could be of interest in the treatment of human colon cancer.
Adenocarcinoma↗
Cytofluorescence localization of adriamycin in resistant colon cancer cells.
A simple fluorescent microscopic method demonstrated that adriamycin was distributed in two cellular compartments of living rat colon cancer cells. Adriamycin accumulated slowly in cytoplasmic granules, probably lysosomes, where it persisted long after the drug was removed from the medium. On the other hand, adriamycin accumulated rapidly in the nucleus, but was rapidly cleared in adriamycin-free medium. Drug efflux from the nucleus was blocked by sodium azide in glucose-free medium or by verapamil, a calcium-blocking agent. When colon cancer cells were cultivated for 1 day or longer in adriamycin-containing medium no nuclear fluorescence was observed. However, the addition of sodium azide to glucose-free medium or verapamil restores the nuclear fluorescence. The colon cancer cells had low sensitivity to adriamycin, but the addition of verapamil strongly enhanced adriamycin toxicity. Thus adriamycin is permanently cleared from the nucleus of rat colon cancer cells through an energy-dependent efflux mechanism, which is blocked by verapamil. The efficiency of this efflux mechanism is enhanced by exposure of the cell to adriamycin. This mechanism could be involved in the resistance of colon cancer to adriamycin.
Animals↗
[False hyperphosphoremia in multiple myeloma. Interference of monoclonal immunoglobulin G with the determination of blood phosphorus level].
A case of pseudohyperphosphataemia detected in a male patient with multiple IgG myeloma is reported. Phosphataemia, measured by a technique without previous deproteinization, reached 5.66 mM before any treatment and varied with treatment-induced changes in monoclonal immunoglobulin levels. Conversely, normal phosphataemia levels were found in blood samples taken before and after treatment when serum was deproteinized. This pseudohyperphosphataemia resulted from an increase in optic density due to interference between monoclonal immunoglobulin and the molybdic reagent used to determine phosphataemia. A retrospective investigation yielded three similar cases: two in patients with myeloma and one in a patient with non-myelomatous monoclonal dysglobulinaemia. A brief prospective study showed that this phenomenon was relatively frequent, as it was found in 2 out of 9 patients with monoclonal immunoglobulin (IgG in all 9 cases). These data indicate that the finding of marked hyperphosphataemia in subjects with monoclonal dysglobulinaemia should always prompt a control assay performed on deproteinized blood.
Electrophoresis↗
[Interpretation of the CA125 kinetics during first line chemotherapy of the ovarian cancer: methodological aspects and characteristic profiles].
Mathematical analysis of CA125 kinetics during first line chemotherapy allows calculation of various biologic parameters which are powerful indicators of the therapeutic efficiency. The purpose of this study is to present an original method of interpretation of CA125 kinetics based on both CA125 profile and its half-life value. The first part of this study reviews the practical modalities of CA125 kinetics analysis, the methods of calculation of the biologic parameters as well as the guidelines of interpretation. The second part of this work is dedicated to the presentation of CA125 profile characteristics in responders to chemotherapy, partially or totally nonresponders to chemotherapy, tumoral growth under treatment and tumor lysis syndrome.
Biomarkers, Tumor↗
[Hypocalcemia induced by cisplatin. Inappropriate parathyroid response due to hypomagnesemia].
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Cisplatin↗
Serum concentrations of amiodarone required for an in vivo modulation of anthracycline resistance.
We demonstrated previously that amiodarone is able to circumvent in vitro the inherent resistance to anthracyclines of the DHD/K12 rat colon cancer cell line. We have now determined in the rat the amiodarone seric concentrations required to enhance the in vitro cytotoxicity of 4'-deoxydoxorubicin (deoDX) against DHD/K12 cells. A maximal deoDX potentiation was obtained in vitro when anthracycline was diluted in the serum of rats receiving at least 75 mg/kg of intravenous amiodarone resulting in seric concentrations of more than 40 micrograms/ml. In patients treated with amiodarone, the mean serum concentrations were 0.9 +/- 0.1 microgram/ml after an one month's oral administration of 200 mg/day, 2.2 +/- 1.0 micrograms/ml after a 24 hr continuous infusion of 300 to 900 mg/day and 5.4 +/- 1.1 micrograms/ml after a brief 3 hrs infusion of 450 mg amiodarone. Such amiodarone concentrations in human serum are much lower than those necessary to produce a significant anthracycline potentiation. In rats receiving amiodarone at a maximal tolerated dose (100 mg/kg) minutes before the injection of 10 mg/kg doxorubicin (DX), we observed an increased accumulation of the anthracycline in the liver and kidney compared to rats receiving DX alone. The DX content was not modified by amiodarone in the other organs studied (heart, lung, spleen and pancreas). An amiodarone pretreatment accelerated the death of rats receiving 5 or 10 mg/kg DX did not provoke lethality for a lower dose of 2.5 mg/kg DX. The very high doses required and the risk of increased toxicity seem to preclude the use of amiodarone for the modulation of anthracycline resistance in cancer patients.
Adjuvants, Pharmaceutic↗
Use of a specific monoclonal antibody for studying the liver metastatic invasion of a rat colon cancer.
A simple model for liver metastasis from colon cancer resulted from the intraportal injection of 2 x 10(7) highly tumorigenic DHD/K12/PROb cells into syngeneic BDIX rats. Early detection and development of cancer invasion were studied by conventional microscopy and immunoenzymatic staining using a specific monoclonal antibody. Metastases developed either from isolated cancer cells early disseminated in sinusoid network or from intraportal microthrombi. An intense immune reaction developed until day 15 after injection but decreased and disappeared at the latest stages of evolution.
Animals↗
mdr 1 gene-expression and villin synthesis in a colon cancer cell line differentiated by sodium butyrate.
Sodium butyrate (NaBu) but not dimethylsulfoxide (DMSO) induced the synthesis of villin, a protein of the brush border microvilli cytoskeleton, in a rat colon cancer cell line. Neither NaBu nor DMSO altered mdr 1-mRNA expression or multidrug resistance (MDR)--associated cellular transport of doxorubicin. These results show that mdr 1 gene expression and activity are independent of other brush border proteins induced by differentiating agents at the apical pole of the epithelial cell.
Animals↗