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B Chauffert

Publications and source records attributed to B Chauffert.

At least 37 records · Page 2Linked to original sources
PubMed1999

Epinephrine enhances penetration and anti-cancer activity of local cisplatin on rat sub-cutaneous and peritoneal tumors.

Despite the theoretical advantages of a high local concentration of anti-cancer drugs, local chemotherapy often fails to produce complete and lasting responses in experimental and human solid tumors. Experiments using Patent Blue dye showed that fluids diffused poorly into tumor mass when injected inside or around s.c. rat tumors in rats. In the same way, Patent Blue dye distributed poorly from the peritoneal cavity into the tumor nodules of rats with peritoneal carcinomatosis. The potent vasoconstrictor, epinephrine (1 mg/kg of body weight) was shown to facilitate the penetration of Patent Blue dye into s.c. and peritoneal rat tumors. Platinum concentration evaluated by micro-PIXE in s.c. DHD/K12/ PROb colon tumors or by atomic absorption spectrometry in DHD/K12/PROb peritoneal tumors was 4- to 12-fold higher when epinephrine was added to local cisplatin. Peri-tumoral or intra-tumoral injection of cisplatin (2 mg/kg) alone does not cure s.c. DHD/K12/PROb colon tumors or GV1A1 glioma tumors in BD IX rats. By contrast, a complete and lasting cure of s.c. tumors was achieved regularly and without skin necrosis when epinephrine was added to intra-tumoral or peri-tumoral cisplatin. Rats with peritoneal-tumor nodules 1 to 2 mm in diameter, and insensitive to i.p. cisplatin alone, were cured when the anti-cancer drug was combined with epinephrine. These experimental results could justify clinical trials using a combination of cisplatin and epinephrine in the treatment of locally growing solid tumors.

Animals↗
PubMed1999

[Intratumoral chemotherapy in an experimental animal model: another therapeutic possibility in cancerology].

OBJECTIVE: Assess the efficacy of intratumoral chemotherapy in a colonic tumor model implanted subcutaneously in the BD IX rat. METHOD: In order to determine their antitumoral effect, 5 anticancer drugs were administered via intravenous and direct intratumoral routes 2 or 10 days after subcutaneous inoculation of tumoral cells. Intratumoral diffusion was evaluated using Patent blue injected directly into the tumoral tissue. Cisplatinum was administered via intratumoral, intravenous and intra-arterial routes to determine the intratumoral and intrarenal concentrations achieved with each of these administration routes. Cisplatinum was also administered via intravenous and intratumoral infusion for 30 minutes to determine the antitumoral effect of each of these routes. RESULTS: Mitomycin and cisplatinum inhibited growth of tumors which had not yet become established and caused advanced stage tumors to regress. For early stage tumors, the intratumoral route was always more effective than the intravenous route. Patent blue diffusion demonstrated a nonhomogeneous intratumoral distribution. Compared with intravenous or intra-arterial infusion, intratumoral infusion gave much higher concentrations of cisplatinum within the tumors and reduced systemic diffusion. At 7 weeks, the antitumoral effect was equivalent for the 2 administration routes while at 13 weeks, the intratumoral treatment was more effective than the intravenous treatment. CONCLUSION: These findings in an experimental animal model demonstrate that intratumoral chemotherapy is more effective than intravenous chemotherapy. It is however still impossible to consistently cure tumors induced in animals.

Amiodarone↗
PubMed1999

[The effect of intra-abdominal temperature on the tissue and tumor diffusion of intraperitoneal cisplatin in a model of peritoneal carcinomatosis in rats].

OBJECTIVE: To evaluate the effects of hyperthermia and hypothermia on the peritoneal and on tumor penetration by intraperitoneal cisplatin. MATERIAL AND METHODS: Twenty day old peritoneal carcinomatosis was obtained after intraperitoneal injection of 1 x 10(6) DHD/K12/PROb cells into BD IX rats. Animals were treated by intraperitoneal infusion of cisplatin (25 micrograms/mL) using hyperthermic (16.6 degrees C), normothermic (37.6 degrees C) or hyperthermic (41.8 degrees C) intraperitoneal chemotherapy. RESULTS: Hyperthermia increased cisplatin concentration in tumoral and diaphragmatic tissues compared to normothermic treatment, while renal concentrations were lower. Hypothermia produced lower cisplatin concentrations in both cancer and peritoneal tissues compared to normothermic treatment. CONCLUSION: These experiments confirmed the pharmacological advantage produced by hyperthermia in cisplatin intraperitoneal chemotherapy.

Abdomen↗
PubMed1998

[Anticancer chemotherapy. Prevention of toxicity].

A MAJOR CHALLENGE: Prevention of short and long term toxicity of chemotherapy is an important challenge in oncology in order to maintain the dose/intensity of protocols and to increase patient comfort. AVAILABLE CHEMOPROTECTORS: Amifostine protects against the blood, kidney and nerve toxicity of cisplatin. Protection is less evident for carboplatin and should be further evaluated for alkylating agents, anthracyclines and taxans. Dexrazoxane protects against the cumulative cardiotoxicity of anthracyclines without reduction of antitumor efficacy. It must be used beyond a cumulative dose of 300 mg/m2 doxorubicin (or equivalent) in responsive patients. Its use in the curative treatment of lymphoma should be assessed by further clinical trials. Mesna must be widely used to prevent the urotoxicity of cyclophosphamide and ifosfamide. An oral preparation is now available for outpatients. Protection of the gonadic function could be achieved by LH-FH analogs in young women. PERSPECTIVES: Due to their high cost and the risk of diminishing the antitumor efficacy in curable diseases, a precise evaluation of present and future chemoprotectors is necessary before wider use.

Amifostine↗
PubMed1998

Contribution of the cyclin-dependent kinase inhibitor p27KIP1 to the confluence-dependent resistance of HT29 human colon carcinoma cells.

We have previously shown that growth of HT29 human colorectal cancer cells at confluence increased their resistance to the cytotoxic agent cisplatin. This study further explores the mechanisms of this resistance phenotype. DNA platination induced by cisplatin exposure is slightly reduced by confluence. However, at an equivalent DNA platination level, non-confluent cells accumulate in the G2/M phase of the cell cycle, demonstrate aberrant mitotic figures and die by apoptosis, while confluent cells progress slowly through the cell cycle, do not reach mitosis and are more resistant to drug-induced cell death. At a molecular level, cisplatin enhances cyclin B and p34cdc2 levels and histone H1 kinase activity in non-confluent, but not in confluent, cells. Furthermore, when HT29 cells reach confluence, expression of the cyclin-dependent kinase inhibitor p27Kip1 increases and cells accumulate in the G0/G1 phase of the cell cycle. Transfection-mediated over-expression of p27Kip1 in non-confluent HT29 cells decreases the cytotoxic activity of cisplatin as well as its ability to trigger apoptosis. Non-confluent HT29 cells over-expressing p27Kip1 are also more resistant to doxorubicin, etoposide and 5-fluorouracil. Our results suggest that p27Kip1 contributes to the confluence-dependent resistance phenotype.

Apoptosis↗
PubMed1998

[Concomitant chemoradiotherapy in the therapeutic strategy of adenocarcinoma of the exocrine pancreas and stomach].

The prognosis of pancreatic adenocarcinoma remains poor, with a 5-year survival rate lower than 5%. Resection, the gold standard treatment, can be performed in less than 10% of patients. Following surgery, the median survival is 12 months for the most favorable cancer patients. Concomitant chemoradiation, as an adjuvant treatment is superior to surgery alone, in terms of survival; controlled trials are currently performed. Neoadjuvant chemoradiation is a new approach, potentially able to increase survival and resection rate. This work justifies the role of these schemes, in terms of modalities and potential advantages. A second part is dedicated to gastric carcinoma, with a review of the current results of chemoradiation, whose efficiency, even though a trend can be observed, remains to be proven. Prospective adjuvant combined treatments are ongoing, in France and in the States.

Antineoplastic Agents↗
PubMed1998

Cancer cell sensitization to fas-mediated apoptosis by sodium butyrate.

Cancer cells often resist Fas-mediated apoptosis even when the Fas receptor is expressed at the cell surface. We show here that human and rat colon cancer cells undergo massive apoptosis when they are exposed to soluble Fas ligand in the presence of sodium butyrate, an agent that induces by itself only a low rate of apoptosis. Sodium butyrate potentiates Fas-dependent apoptosis in seven out of eight colon cancer cell lines. Sodium butyrate does not increase Fas receptor cell surface expression and does not modify cell levels of Bcl-2, Bcl-xL, Bcl-xS and Bax. Sodium butyrate also induces tumor cell sensitization to the apoptotic effect of the combination of TNF-alpha and IFN-gamma, but it does not modify the level of the FADD/Mort1 adaptator molecule, at the connection between Fas- and TNF-dependent apoptosis pathways. Because the clinical toxicity of butyrate is low, its ability to enhance Fas-signal delivery in cancer cells could be of therapeutic interest.

Adaptor Proteins, Signal Transducing↗
PubMed1997

HSP27 as a mediator of confluence-dependent resistance to cell death induced by anticancer drugs.

Resistance of colorectal cancer cells to chemotherapeutic drugs increases as cells reach confluence. Here we show that the small stress protein HSP27, which has been described to block necrotic and apoptotic cell death, accumulates in confluent human colorectal cancer cell lines HT-29 and Caco2. Cell confluence also induces HSP27 phosphorylation and changes in its intracellular distribution. We also show that overexpression of human HSP27 by transfection of HT-29 cells increased the resistance of cells to doxorubicin or cisplatin and prevented drug-induced apoptosis. Interestingly, nonconfluent HSP27-transfected cells and confluent control cells in which HSP27 is expressed at the same level displayed a similar drug resistance. HSP27-transfected cells did not exhibit an enhanced resistance when they reached confluence, nor was there an increased accumulation of HSP27. We have previously shown that HSP27 expression blocks tumor necrosis factor-induced cell death as a result of decreasing intracellular reactive oxygen species (ROS). Here we show that HSP27 overexpression in HT-29 cells, obtained either by transfection or by growing the cells at high density, correlated with a significant ROS decrease. We conclude that cell confluent-dependent HSP27 accumulation, probably due to its ability to decrease ROS levels, is essential for the establishment of the resistance of colorectal cancer cells when reaching confluence.

Apoptosis↗
PubMed1997

Retroperitoneal fibrosis and infection of an aortic graft prosthesis: diagnosis and therapeutic problems.

The occurrence of a retroperitoneal fibrosis (RPF) after an aorto-bifemoral bypass is unusual. A case of RPF as a complication of an infection of the graft prosthesis is reported. Computed tomography and magnetic resonance imaging prove useful in diagnosing graft infection: they may reveal periprosthetic gas or perigraft fluid persisting for several months after surgery. However, they may fail when they are performed too early, and repeat performance is suggested.

Aged↗