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Biomedical subjects

B Chauffert

Publications and source records attributed to B Chauffert.

At least 19 recordsLinked to original sources

[Treatment of cancer and hematological malignancy in elderly people: oncogeriatrics as a discipline for the future (Part I): geriatric evaluation and management of solid tumors].

PURPOSE: Fifty percent of cancer arise in people older than 65 year-old. Most clinical trials in cancer treatment are limited in patients younger than 65 year-old. We review literature describing particularity of cancer treatment in elderly patients. CURRENT KNOWLEDGE AND KEY POINTS: Therapeutic decisions should be based on an estimation of the patient's life expectancy, and risks and benefits should be weighted up accordingly. Geriatric oncology is made of a geriatric evaluation of patient and of knowledge of clinical trial about elderly patients. FUTURE PROSPECTS AND PROJECTS: We present in this issue the principle of geriatric evaluation and the results of recent clinical trial on elderly cancer patients.

Age Factors↗

Concurrent lymphoma and metastatic breast carcinoma in the axillary, confounding sentinel lymph-node biopsy.

We describe the case of a female patient who presented with the concurrence of two tumors, breast cancer and low grade lymphoma, in different nodes but in the same axillary lymphatic site. The sentinel node biopsy procedure for the detection of carcinoma cells in two well-identified sentinel nodes which had been colonised by lymphoplasmocytic cells was negative. Tumor collision lead to a mistake in the appropriate staging of the breast tumor by sentinel lymph-node biopsy. We believe that sentinel lymph-node biopsy should be avoided in cases of lymphoma.

Axilla↗

New ursolic and betulinic derivatives as potential cytotoxic agents.

Fifteen new ursolic and betulinic triterpenoids, bearing various functionalities at C-3 and C-28 were synthesized as potential cytotoxic agents. All compounds were obtained by a hemisynthetic route via ursolic and betulinic acids. Preliminary screening of these compounds on human HT 29 colon cancer cells revealed inhibitory activity for three of them. Beta-D-Glucopyranosyl-3beta-hydroxyurs-12(13)-en-28-oate 1c, 3beta-3-(3-pyridyl)-prop-2-enoyloxyurs-12(13)-en-28-oic acid 1i and the potassium salt of 3beta-cinnamoyloxylup-20(29)-en-28-oic acid 2d demonstrated cytotoxic activity in the micromolar range: 8.0, 45.0 and 8.0 microM, respectively.

Antineoplastic Agents↗

[Evaluation of povidone abdominal washing for prevention of peritoneal cancer cell seeding: experimental study in the rat].

GOAL: The aim of the study was to evaluate the in vitro cytototoxicity of diluted povidone iodine on colon cancer cells and its in vivo antitumoral effect in a model of peritoneal carcinomatosis in the rat. METHODS: Cell cytotoxicity of a povidone iodine diluted solution was assessed, in vitro, on rat colon cancer cells (DHD/K12/PROb) and human colon cancer cells (HT29). The antitumoral effect of diluted povidone iodine washing was measured in BDIX rats after the intraperitoneal inoculation of 10(6) DHD/K12/PROb cells. Results were compared to an abdominal washing within a 9 g/l salinel solution. In one experiment, peritoneal scars and a colocolic anastomosis were performed after the injection of cancer cells. RESULTS: A short 10 min incubation of human and rat colon cancer cells with diluted povidone iodine resulted in a complete cell killing. In animals, a peritoneal washing with 1% diluted povidone iodine completely inhibited the tumor growth in parietal peritoneum. However, development of peritoneal tumor nodules was not inhibited in the omentum, in scarified peritoneum or in intestinal anastomosis. CONCLUSIONS: Despite its high in vitro efficacy, diluted povidone iodine has an incomplete effect in the prevention of peritoneal carcinomatosis, with only a partial inhibition in scarred peritoneum epiploïc area and intestinal anastomosis. In contrary, it procures a complete inhibition of tumor growth in normal peritoneum.

Animals↗

Identification of tumor-infiltrating macrophages as the killers of tumor cells after immunization in a rat model system.

Immunization can prevent tumor growth, but the effector cells directly responsible for tumor cell killing in immunized hosts remain undetermined. The present study compares tumor grafts that progress in naive syngeneic rats with the same grafts that completely regress in hosts preimmunized with an immunogenic cell variant. The progressive tumors contain only a few macrophages that remain at the periphery of the tumor without direct contact with the cancer cells. These macrophages do not kill tumor cells in vitro. In contrast, tumors grafted in immunized hosts and examined at the beginning of tumor regression show a dramatic infiltration with mature macrophages, many of them in direct contact with the cancer cells. These macrophages are strongly cytotoxic for the tumor cells in vitro. In contrast to macrophages, tumor-associated lymphocytes are not directly cytotoxic to the tumor cells, even when obtained from tumor-immune rats. However, CD4(+) and CD8(+) T cells prepared from the regressing tumors induce tumoricidal activity in splenic macrophages from normal or tumor-bearing rats and in macrophages that infiltrate progressive tumors. These results strongly suggest that the main tumoricidal effector cells in preimmunized rats are macrophages that have been activated by adjacent tumor-immune lymphocytes.

Animals↗

[Intraperitoneal chemo-hyperthermia with "overflow" open abdomen].

The authors report an original procedure of open-abdomen intraperitoneal chemo-hyperthermia. The skin edges are watertightly stapled with a soft "abdominal cavity expander", supported by a Thompson self-retaining retractor positioned over the abdomen. So, the level of the liquid can be widely raised above the level of the skin edges. The anterior wall peritoneum, the wall edges are constantly exposed to the liquid. Large amplitude movements become possible: introduction into the abdomen of two forearms, even two arms, does not induce loss of any liquid. The small bowel, the stomach can be partially exteriorized. It becomes very easy to expose all the peritoneal spaces, to maintain an homogeneous hyperthermia within the abdomen, while using only one inflow drain, and one outflow drain.

Abdominal Neoplasms↗

[Expression of p21 WAF1/CIP1 protein in colorectal cancers: study of its relation to p53 mutation and Ki67 antigen expression].

Mutations of the p53 gene are the most common genetic alteration in malignant human tumors. A cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is thought to be an important mediator of p53-induced cell cycle arrest. Although numerous studies have reported p53 expression and mutation in colorectal cancer few of them have correlated p53 expression with that of its downstream effector p21 and with the proliferation index as measured by expression of the Ki67 nuclear antigen. We studied p53, p21 and Ki67 expression by immunohistochemistry and molecular biology in 35 colorectal carcinomas. We compared these findings with each other and with clinical factors. Sixty three percent of tumors expressed p53 whereas seventy one percent expressed p21WAF1/CIP1. In adenocarcinomas, p21 staining was heterogeneous: p21-reactive cells were seen in the most differentiated areas. There was no correlation between p21WAF1/CIP1 and p53 expression, p53 mutation, Ki67 expression or clinical factors such as sex or location of the tumor. On the other hand, there was a statistical relationship between p21 expression and survival: our results indicated an association between high p21 expression and lower stages p21WAF1/CIP1 appears to be induced independently of p53 in these tumors and may be associated with differentiation rather than proliferation.

Adenocarcinoma↗

Bidentatoside I, a new triterpene saponin from Achyranthes bidentata.

Bidentatoside I (1) is a new triterpene saponin bearing an unusual dioxopropionic acid unit, isolated from the roots of Achyranthes bidentata. Structural elucidation was performed mainly by chemical and homo- and heteronuclear 2D NMR techniques. This compound did not show any potentiation of the in vitro cytotoxicity of cisplatin in the HT 29 human colon cancer cell line.

Antineoplastic Agents↗

Pre-clinical study of the epinephrine-cisplatin association for the treatment of intraperitoneal carcinomatosis.

We have previously shown that intraperitoneal (i.p.) epinephrine enhances tumour penetration and anti-cancer activity of i.p.-administered cisplatin in rats with peritoneal carcinomatosis. Here, we show a direct correlation between the i.p. epinephrine concentration and cisplatin accumulation in rat peritoneal tumour nodules up to a concentration of 5 mg/l. This concentration leads to a maximal 3.7-fold increase of tumour platinum content and a maximal vasoconstriction of the peritoneal and tumour superficial microcirculation when registered by a laser doppler probe. Further, epinephrine half-life was 20.8+/-3.6 min in the peritoneal cavity of two laparotomized pigs. In these animals, epinephrine plasma concentration, heart rate and systolic blood pressure were dependent on the intraperitoneal dose of epinephrine, and life-threatening signs were not observed in either animal. In conclusion, a 5 mg/l concentration of epinephrine could be safely maintained in peritoneal fluid by regular replacement. This concentration is sufficient to maintain a constant vasoconstriction of the peritoneal and tumoral microvascular bed, and enhance the slow diffusion of cisplatin into peritoneal tumour nodules in the course of per-operative intraperitoneal chemotherapy.

Animals↗

Increased cytotoxicity and stability of Lipiodol-pirarubicin emulsion compared to classical doxorubicin-Lipiodol: potential advantage for chemoembolization of unresectable hepatocellular carcinoma.

There is no well-defined curative treatment for advanced and unresectable hepatocellular carcinoma. The widely used transarterial chemoembolization (TACE) with a doxorubicin-Lipiodol emulsion has not been shown to improve survival in randomized studies. Further, obstruction of the hepatic artery used in the procedure is badly tolerated in patients with cirrhosis. Drugs with a more rapid penetration into the cancer cells are likely to eliminate the need for obstruction of the hepatic artery. We therefore compared the cytotoxicity of another anthracycline pirarubicin with that of the commonly used doxorubicin. In this report, we show that pirarubicin has a greater in vitro cytotoxic effect than doxorubicin on the HepG2 and Hu-H7 human hepatoma cell lines. Pirarubicin emulsion with Lipiodol is more stable at 37 degrees C than doxorubicin-Lipiodol. Moreover, pirarubicin accumulates at a greater extent in the oil phase, permitting Lipiodol to act as a slow-releasing vector for the anthracycline. Further, amiodarone, a multidrug resistance inhibitor, was shown to decrease the intrinsic resistance of HepG2 and Hu-H7 cells to both anthracyclines, and the presence of polysorbate 80 in the amiodarone preparation increased the stability of the anthracycline-Lipiodol emulsions. We therefore conclude that pirarubicin is a better candidate for TACE than doxorubicin. The rapid and increased cytotoxicity of pirarubicin on hepatoma cancer cells and the stability of the pirarubicin-Lipiodol amiodarone emulsion could avoid the complete obstruction of the hepatic artery by Gelfoam sponges, and provide a better tolerated method of TACE in patients with latent liver insufficiency.

Amiodarone↗

Hepatic arterial infusion of cisplatin diluted in hypotonic 25 g/l glucose solution administered in balloon-occluded hepatic artery: experimental rationale and clinical pilot study.

Reduced osmolarity in incubation medium was previously shown to increase in vitro cellular accumulation and cytotoxicity of cisplatin on cancer cells. We confirmed in the present work that cisplatin diluted in an hypotonic 25 g/l glucose solution (124 mOsm) was dramatically more cytotoxic in vitro than cisplatin diluted in normotonic 9 g/l NaCl (300 mOsm) on the human HT29 colon and MCF7 breast cancer cells. We conducted then a pilot clinical study on the administration of cisplatin diluted in hypotonic 25 g/l glucose solution given through the balloon-occluded hepatic artery for the treatment of liver metastases from colon or breast cancer tumors. Nine patients (5 men, 4 women; mean age 58, range: 44-71) with confirmed isolated, unresectable metastases from colorectal (7) or breast (2) tumors were included in this study and a total of 23 cycles were administered (2.55 per patient; range 1-5) with an average dose of 50 mg cisplatin (range: 12.5-100). Hepatic artery dissection due to balloon injury with partial or complete arterial obstruction were encountered in 2 patients. Pain in the liver and epigastric area was the main symptom which was constant and intense during the IAH cisplatin injection. Fever > 38 degrees C was observed in 15/23 cycles and increase of creatinine in 1/23 cycles. Transient increase of hepatic transaminases without change in prothrombin time was registered in all patients. However one patient who received the highest dose of 100 mg cisplatin developed a persistent but reversible clinical jaundice and a transient increase in prothrombin time. One patient achieved a partial response (12 weeks), 7 had stable disease (mean duration: 6 weeks) and one had a progressive disease. Hepatic arterial infusion of cisplatin diluted in hypotonic 25 g/l glucose solution and administered through the balloon-occluded hepatic artery is a feasible approach. Total dose of cisplatin in hypotonic glucose solution will not exceed 80 mg by cure in a further phase II study.

Adult↗

[Concomitant chemoradiotherapy and preoperative radiotherapy in exocrine pancreatic adenocarcinoma].

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. Concomitant chemoradiation, as an adjuvant treatment could be 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. Finally, current data regarding intraoperative irradiation are exposed.

Adenocarcinoma↗

A new major triterpene saponin from the roots of Cucurbita foetidissima.

Foetidissimoside B (1), a novel triterpene saponin, was isolated from the roots of Cucurbita foetidissima. Based on spectroscopic data, especially direct and long-range heteronuclear 2D NMR analysis and on chemical transformations, the structure of 1 was elucidated as 3-O-beta-D-glucuronopyranosyl-echinocystic acid 28-O-beta-D-glucopyranosyl-(1-->3)-beta-D-xylopyranosyl(1-->3)-[beta- D-xylopyranosyl (1-->4)]-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside . Compound 1 did not show any ability to potentiate in vitro cisplatin cytotoxicity in a human colon cancer cell line.

Carbohydrate Conformation↗

Phase I study of cinchonine, a multidrug resistance reversing agent, combined with the CHVP regimen in relapsed and refractory lymphoproliferative syndromes.

Overexpression of P-glycoprotein (P-gp) in cancer cells reduces intracellular accumulation of various anticancer drugs including anthracyclines and vinca alkaloids. This multidrug resistance (MDR) phenotype can be reversed in vitro by a number of non-cytotoxic drugs. We have identified the quinine's isomer cinchonine as a potent MDR reversing agent, both in vitro and in animal models. Here, we report an open phase I dose escalation trial in patients with refractory or relapsed malignant lymphoid diseases. Cinchonine dihydrochloride was administered by continuous i.v. infusion for 48 h and escalated over five dose levels ranging from 15 to 35 mg/kg/d. Cinchonine infusion started 24 h before i.v. doxorubicin (25 mg/m2), vinblastine (6 mg/m2), cyclophosphamide (600 mg/m2) and methylprednisolone (1 mg/kg/d) (CHVP regimen) and lasted for 24 h after chemotherapy infusion. Thirty-four patients received 87 cycles of CHVP/cinchonine. The MTD of cinchonine administered by continuous i.v. infusion was 30 mg/kg/d. Prolonged cardiac repolarization was the main dose-limiting toxicity. No ventricular arrhythmia including 'torsade de pointes' was observed. An MDR reversing activity was identified in the serum from every patient and correlated with cinchonine serum level. When infused at 30 mg/kg/d, cinchonine demonstrated a limited influence on doxorubicin pharmacokinetic. We conclude that i.v. infusion of cinchonine might be started 12 h before MDR-related chemotherapy infusion and requires continuous cardiac monitoring but no reduction of cytotoxic drug doses.

Adult↗

[Intraperitoneal cisplatin plus epinephrine and surgical debulking for the treatment of advanced peritoneal carcinomatosis in the rat].

OBJECTIVE: To evaluate and compare the effects of cytoreductive surgery with intraperitoneal cisplatin and epinephrine on peritoneal carcinomatosis in the rat. MATERIAL AND METHODS: Twenty-day old peritoneal carcinomatosis was obtained after intraperitoneal injection of 1 x 10(6) DHD/K12/PROb cells into BDIX rats. The surgical treatment included electric fulguration of the peritoneal tumors with spleen and omentum removal while intraperitoneal chemotherapy included platinum (3 mg/kg) associated with epinephrine (2 mg/kg). RESULTS: Surgery did not increase rat survival unlike cisplatin or cisplatin/epinephrine chemotherapy. Intraperitoneal chemotherapy alone with cisplatin +/- epinephrine increased survival but did not provide cure. Surgery followed by intraperitoneal cisplatin and epinephrine cured four out of five twenty-day old peritoneal carcinomatosis. CONCLUSION: Surgery combined with intraperitoneal cisplatin and epinephrine could be an efficient treatment for peritoneal carcinomatosis in man.

Animals↗

[Early signs of systemic disease in patients taking minocycline chlorhydrate].

BACKGROUND: Search for etiology in young subjects with joint disease must take into consideration causes other than reactional arthropathy or systemic disease. CASE REPORTS: Two young subjects consulted for joint pain involving various joints. Physical examination did not reveal any other abnormality. Serum tests were positive for antinuclear antibodies and/or showed moderately and persistently elevated transaminases. History taking revealed that these subjects had been taking minocyclin chlorhydrate for several months, or even years, for acne. Joint pain subsided with drug withdrawal and serum tests returned to normal. DISCUSSION: Long-term treatment with minocylin chlorhydrate should always be included in the search for an etiology in patients presenting joint pain.

Adolescent↗