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B Chauffert

Publications and source records attributed to B Chauffert.

At least 55 records · Page 3Linked to original sources
PubMed1997

[Fight against cancer of the exocrine pancreas: stagnation or progress? The point of view of the Fondation française de cancérologie digestive (FFCD)].

This paper updates recent trends concerning ductal pancreatic cancer. Knowledge of the cellular mechanisms has improved, and new developments in imaging allow a more accurate staging. Although operative mortality sharply decreased during these last 15 years, the prognosis of pancreatic carcinoma remains dismal, due to late diagnosis, as only one out of ten patients is considered for curative resection. Therapeutic research groups, and among them the Fondation française de cancérologie digestive (FFCD), do their best to develop new therapeutic strategies, including post-operative or preferentially pre-operative radio-chemotherapeutic adjuvant treatments, and to improve chemotherapy in metastatic cancers.

Adenocarcinoma↗
PubMed1996

Inconstant association between 27-kDa heat-shock protein (Hsp27) content and doxorubicin resistance in human colon cancer cells. The doxorubicin-protecting effect of Hsp27.

To investigate the role of the small 27-kDa heat-shock protein (Hsp27) in the intrinsic resistance of colon cancer cells to doxorubicin, we modified Hsp27 expression either genetically by transfection or pharmacologically by cisplatin treatment. HT-29 cells were transfected with a full-length Hsp27 construct in the sense or antisense orientation. We found a good correlation between cell survival after doxorubicin treatment and Hsp27 content. A similar correlation was found for the thermoresistance of the Hsp27-transfected cells. In contrast, the sensitivity of the different transfected cells to 5-fluorouracil was not modified. cis-Platinum(II)diammine dichloride (cisplatin) treatment of HT-29 or Caco2 cells dramatically increased their Hsp27 mRNA and protein content. Accordingly, the cells became thermoresistant. Contrary to what has been previously assumed, however, cell resistance to doxorubicin was reduced. Our data suggest that the decreased resistance of the cells to doxorubicin may be due to a concomitant increase of topoisomerase II expression, the main target of anthracyclines. In conclusion, although Hsp27 seems to participate in the natural resistance of colon cancer cells to anthracyclines, its increase after cisplatin treatment is not associated with a decreased cytotoxicity to doxorubicin.

Cell Survival↗
PubMed1996

Combined chemotherapy and radiotherapy for esophageal carcinoma in a hemodialyzed patient. Long-term survival.

The use of antimitotic chemotherapy in hemodialysis patients is not yet well codified, and each individual decision remains difficult. We report the case of a 68-year-old hemodialyzed man who developed a squamous cell carcinoma of the upper third of the esophagus. Necessarily disabling surgery was rejected, and three courses of combined radio- and chemotherapy with 5-fluorouracil and cis-platinum were performed without decreasing standard doses. The percentage of drugs removed during hemodialysis sessions was low; peak and residual platinum plasma concentrations were only slightly above those observed in normal renal function patients. The treatment was perfectly well tolerated, and tumor response was satisfactory without any relapse for 3 years. This observation suggests that hemodialysis patients could benefit from such 'full therapies', if necessary, without major adverse effects.

Aged↗
PubMed1995

Circumvention of confluence-dependent resistance in a human multi-drug-resistant colon-cancer cell line.

Colorectal adenocarcinomas are inherently resistant to anthracyclines and other topoisomerase-II inhibitors. Resistance to doxorubicin of colon cancer cells (Caco2) depends on 2 main mechanisms. The first is typical multi-drug resistance, characterized by the mdr1 gene and its product the P170 membrane glycoprotein. P170 effluxes anthracyclines out of cancer cells and is antagonized in vitro by verapamil. The second mechanism, which develops when cell-culture density increases, we have designated confluence-dependent resistance. Confluence-dependent resistance depends on the reduced topoisomerase II content of the G0/G1-phase cells which accumulate in the confluent population. We show here that short treatments of confluent Caco2 cells with slightly toxic concentrations of DNA-damaging agents (cisplatin, melphalan or mitomycin C) produced a transient accumulation of cells in S- and G2/M-phases of the cell cycle. Concomitantly with the increase in the S-phase population, the topoisomerase II cellular level and the sensitivity of cells to doxorubicin were greatly enhanced. Overcoming confluence-dependent resistance through S-phase accumulation and inhibition of multi-drug resistance by verapamil were fully additive, and a nearly complete reversal of confluent Caco2 cells' resistance to doxorubicin was obtained when both strategies were combined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

[Perforation of colonic diverticulum under corticoids: a complication to be known and recognized].

Glucocorticoids can produce acute perforation of colonic diverticula and peritoneal infection. We report two observations in which patients presented a peritoneal collection with no specific clinical signs. The diagnosis was considered after C-T scan or ultrasans. Residues of contrast liquid, after an earlier X-ray exploration, have made the diagnosis of diverticula easier. In one case, corticosteroids were started as a short cure for the treatment of a myeloma. In the other case, patient received a long term corticosteroid therapy at low dose for an asthmatic disease. The perforation was induced by an increased dosage. Diverticular perforations result from inhibition of synthesis of prostaglandins who have the beneficial property of "cytoprotection" and from the immunosuppressive action of glucocorticoids which favour the diffusion of the peritoneal infection. diffusion of the peritoneal infection.

Aged↗
PubMed1995

Cinchonine per os: efficient circumvention of P-glycoprotein-mediated multidrug resistance.

We have previously suggested that quinine and cinchonine could be good candidates for the clinical circumvention of multidrug resistance (MDR) in haematological malignancies because of their tolerance and their retained efficacy in serum. We have also shown that cinchonine was more efficient than quinine as an anti-MDR agent in vitro, ex vivo and in vivo after parenteral administration. Here, we report that cinchonine administered per os (po) is much more active than quinine po in circumventing MDR in rats bearing resistant colon tumours. The pharmacokinetics of cinchonine and quinine administered po in rat are shown to be very different. Cinchonine demonstrates a greater absolute bioavailability than quinine (44% versus 30%, respectively). Its serum concentration correlates with the anti-MDR activity measured ex vivo and in vivo. Cinchonine administered po does not significantly modify the pharmacokinetics of intravenous doxorubicin (DXR). However, cinchonine induces a significant increase of DXR uptake in organs which express the mdr1 gene (liver, kidney, lung). When associated with VAD (vincristine, adriamycin, dexamethasone) combined therapy in rats, cinchonine does not significantly increase the toxicity of the cytotoxic drugs. Based on these experimental data, a phase I clinical trial is currently in progress to test the tolerance of this potent MDR-reversing agent administered po.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Confluence dependent resistance (CDR) to doxorubicin and E-cadherin expression in murine mammary cells.

Confluence dependent resistance (CDR) is one of the principal mechanisms by which solid tumor cells resist anthracyclines. CDR is thought to be mediated by cell-cell contact which increases the fraction of non-proliferating resistant cells in a post confluence monolayer culture. As E-cadherin is a major Ca2+ dependent adhesion molecule, involved in cell-cell adhesion, differentiation and polarity of normal and cancerous epithelial cells, we decided to investigate its involvement in the CDR mechanism. In order to do this, we measured the intracellular accumulation and the cytotoxicity of doxorubicin (DXR) in four subclones, derived from the same parental murine mammary cell line (NMuMG), differing in their expression of E-cadherin. A significant reduction in DXR accumulation and cytotoxicity was observed in NM-f-ras-TD-CAMx, which expresses E-cadherin, suggesting that E-cadherin could play a role in the increase of drug resistance observed in confluent cancer cells.

Animals↗
PubMed1994

In vivo and in vitro invasiveness of a rat colon-cancer cell line maintaining E-cadherin expression: an enhancing role of tumor-associated myofibroblasts.

In various cell systems, an inverse relationship was found between expression of E-cadherin, a molecule involved in the Ca(2+)-dependent homophylic cell-to-cell attachment of epithelial cells, and the capacity to invade extracellular matrix gels or normal tissues in vitro. DHD/K12/TRb (PROb) cells, maintained as a cell line derived from a rat colon carcinoma, homogeneously expressed in vitro immunoreactive E-cadherin, which was functional as shown in cell dissociation-reassociation assays. PROb cells were found to be non-invasive in 3 different assays in vitro. However, tumors resulting from a s.c. injection of PROb cells into syngeneic BD-IX rats were invasive, although PROb cells maintained E-cadherin expression in the tumors. Cells from a freshly dissociated PROb tumor showed, not only PROb cells but also tumor-associated myofibroblasts and were able to cross a Matrigel-coated filter. PROb tumors were indeed infiltrated by numerous myofibroblasts, mainly located at the invasive edge of the tumor. Cells from an established culture of tumor-infiltrating myofibroblasts were able to confer upon PROb cells invasiveness through Matrigel-coated filter or into chick-heart fragments. PROb cells maintained their capacity to express E-cadherin after myofibroblast-enhanced Matrigel invasion. Tumor-associated myofibroblasts, but not PROb cells, secreted a 72-kDa collagenase that could play a role in tumor-cell invasion. These results strongly suggest that cells from the tumor stroma, and more specifically myofibroblasts, may be involved in the invasiveness of epithelial tumor cells in vivo, even when E-cadherin expression prevents tumor-cell invasiveness in different in vitro assays.

Animals↗
PubMed1994

[Association of infectious aneurysm and microbial spondylodiscitis: physiopathological hypotheses, diagnostic and therapeutic approach].

Two years after a Staphylococcus aureus septicaemia, in a patient with dermatopolymyositis occurred an infectious aneurysm of abdominal aorta with contiguous pyogenic spondylodiscitis. Coexistence of both pathologies is rare and physiopathological mechanisms still remain uncertain. However, many arguments in the present case report are in favour of the initial responsibility of an infectious aneurysm. Main interest in early diagnosing infectious aneurysm, allowed by new investigations such as magnetic resonance imaging and marked leukocyte bone scanning, is the prevention of major complications. Antibiotherapy and surgical removal of infectious aneurysm must be quickly achieved in every case.

Aneurysm, Infected↗
PubMed1994

Deleterious effect of serum proteins on the amphotericin B-induced potentiation of cisplatin in human colon cancer cells.

Inherent resistance of colon cancer cells to cis-diamminedichloroplatinum(II) (CDDP) is partly attributed to reduced drug penetration through plasma membrane. Amphotericin B (AmB), a polyene antifungal antibiotic, has been shown to increase CDDP penetration and cytotoxicity on several non-digestive cancer cell lines. We demonstrated here that AmB dramatically increases the penetration of CDDP, and to a lesser extent that of carboplatin (Carbo-P) and oxaloplatin (L-OHP), in the primary resistant HT 29 human colon cancer cells when drug incubation is performed in serum-free medium. The cytotoxicity of CDDP but not that of Carbo-P and L-OHP was increased by AmB. However, AmB-induced potentiation of CDDP penetration and toxicity was almost completely abolished when cell incubation was performed in presence of human serum. We investigated whether the dilution of human serum by a high osmotic power gelatine solution (Lomol) could restore the positive effect of AmB on CDDP accumulation in HT 29 cells. Incubation of cells with CDDP and AmB in pure Lomol resulted in a 6-fold increase in platinum cellular content. However, addition of serum (25%) in Lomol solution reduced to only 2-fold the increase in platinum cellular content provoked by AmB. These disappointing results show that AmB is probably uninteresting as a modulator of CDDP resistance in clinical practice. The use of haemodilution to restore the positive AmB effect on platinum cellular accumulation cannot be warranted.

Adenocarcinoma↗
PubMed1994

Liposomal mitoxantrone for the local treatment of peritoneal carcinomatosis induced by colon cancer cells in mice.

Since liposomes are slowly resorbed from serous cavities, they may constitute a valuable tool for the treatment of peritoneal carcinomatosis. We prepared mitoxantrone (MXN)-liposomes with various lipid compositions and checked their antitumoral activity on a peritoneal carcinomatosis induced by a colon cancer cell injection (1 x 10(5) C51 cells) in BALB/c mice. MXN entrapment in liposomes was rapid and stable due to its high lipophilicity. MXN carried in phosphatidylcholine: cholesterol (2:1; G-liposomes) displayed a reduced toxicity in mice compared to the free drug. When tested at a non-toxic dose (2 mg/kg), MXN entrapped in G-liposomes proved to be as efficient as the free drug. At a higher MXN dose (3 mg/kg), both G-liposomes and phosphatidylcholine:cholesterol:dipalmitoylphosphatidylethanolamine (7:2:1) liposomes, loaded with MXN, significantly increased the life span of mice compared to the free drug and six other liposome formulations. Increase in the MXN therapeutic index, when used in the liposomal form, could then merit further clinical investigations in regard to patients with malignancies confined to serous cavities.

Animals↗
PubMed1994

Comparative effects of quinine and cinchonine in reversing multidrug resistance on human leukemic cell line K562/ADM.

We have previously suggested that quinine and cinchonine could be good candidates for clinical circumvention of multidrug resistance (MDR) in hematological malignancies because of their tolerance and their retained efficacy in serum. In the present study, we have used the well-characterized multidrug resistant human leukemic cell line K562/ADM to compare the effect in vitro of quinine and cinchonine on doxorubicin, mitoxantrone, and vincristine uptake and cytotoxicity. In serum-free medium, quinine induced a dose-dependent increase of doxorubicin uptake reaching about 200% at 40 microM, while it had a slight and no effect on mitoxantrone and vincristine uptake respectively. In the same conditions, cinchonine induced a rapid and significant increase in the accumulation of the three drugs, reaching a plateau phase between 5 and 10 microM. Quinine and cinchonine induced both potentiation of doxorubicin, vincristine and mitoxantrone cytotoxicity in K562/ADM cells. However, quinine reached a plateau phase at 10 microM, while cinchonine had a maximal effect at 5 microM and was significantly more potent at low concentrations. When diluted in plasma, cinchonine was less bound to proteins than quinine. The free fraction of alkaloids was 37-55% for cinchonine and 20-30% for quinine. Cinchonine-induced enhancement of vincristine cellular accumulation was little modified by plasma proteins. When incubated in whole blood, the fraction of cinchonine trapped in red blood cells was rapidly and completely exchangeable with plasma. We conclude that cinchonine is a stronger inhibitor of MDR than quinine.

Antineoplastic Agents↗
PubMed1993

Kinetic resistance to anticancer agents.

Adherent epithelial cancer cells, such as colon cancer cells, are much more resistant to anthracyclines and to many other major anticancer agents when the cell population reaches confluence. Our purpose is to analyze the mechanisms of this confluence dependent resistance (CDR) that is probably the major cause of the natural resistance of solid tumors to chemotherapy. Some drugs (anthracyclines, etoposide and vincristine) but not others (cisplatin, melphalan and 5-fluorouracil) accumulate less in confluent than in nonconfluent cells. A decrease of the passive transmembrane drug transport in confluent cells is associated to a reduced membrane fluidity. However, the predominant mechanism of CDR is an increase in the intrinsic resistance of the DNA to the drug-induced damage. This mechanism is now relatively well understood for anthracyclines and etoposide that act mainly through an inhibition of the topoisomerase II: as the enzyme level is low in slowly proliferating confluent cells, the number of drug-induced DNA strand breaks is lower than in rapidly growing nonconfluent cells which highly express the topoisomerase II gene. Mechanisms of CDR for the other drugs are less clear and could involve an increase in the ability to repair damaged DNA. Attempts to circumvent CDR could consist in the stimulation of the cell proliferation by hormones or growth factors, or in the recruitment of quiescent cells into the S and G2 phases by previous treatment of confluent cells with infratoxic concentration of DNA-damaging agents.

Animals↗
PubMed1993

[Bone metastasis of hepatocellular carcinoma. Apropos of 22 cases].

There have been few studies and case-reports of bone metastases from hepatocellular carcinoma. To determine the characteristics of these metastases, we retrospectively studied 22 patients in whom the diagnosis was established either on the basis of concomitant occurrence of malignant bone lesions and hepatocellular carcinoma in the absence of other detectable malignant disease (n = 15) or on the basis of histological evidence of bone metastasis from an hepatocellular carcinoma (n = 7). There were 21 males and one female. Mean age was 62.5 years. Most patients (88.2%) had chronic alcohol abuse. The bone metastases occurred as the first manifestation of the liver cancer in half the cases (11/22). Time interval between onset of bone symptoms and admission was less than one month in 6 of 11 patients; mean interval was 7.4 weeks. Hepatomegaly was found upon initial physical evaluation in 9 of 11 patients. Pain was the main symptom of bone disease (18/22). Palpable bone masses were found in 6 of 22 patients. Purely osteolytic lesions were seen on roentgenograms in every case; rupture of the cortex and spread to adjacent soft tissues were common findings. The radionuclide bone scan was normal in four of 12 patients. An advanced primary hepatic tumor was found in 84.2% of cases. Histologic examination of bone specimens established the diagnosis of metastasis from a hepatocellular carcinoma in 7 of 9 patients (77.8%). Severe bleeding occurred during one of the nine biopsy procedures. Patients were given symptomatic treatment. Systemic chemotherapy was used in five patients, unsuccessfully. Median survival was three months.

Bone Neoplasms↗
PubMed1993

[Dilated cardiomyopathy disclosing dermatopolymyositis. Management].

Cardiac involvement in dermatopolymyositis is common but rarely symptomatic. Cardiac failure as the presentation is very rare. No correlation exists between the severity of muscular involvement and cardiac involvement. Myocarditis is not uncommon and must be borne in mind if CK MB are above 3% of total CK. It is always associated with electrocardiographic abnormalities. Corticosteroids remain first line treatment. They generally lead to regression of cardiac problems which are usually of secondary importance. If cardiac involvement is severe, the spectacular action of venoglobulins should lead to their use being envisaged from the outset, combined with corticosteroids.

Cardiomyopathy, Dilated↗