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Biomedical subjects

G Legrand

Publications and source records attributed to G Legrand.

At least 19 recordsLinked to original sources
PubMed2006

Epidermal growth factor-induced neuroendocrine differentiation and apoptotic resistance of androgen-independent human prostate cancer cells.

Neuroendocrine differentiation (NED) has been implicated in prostate cancer progression and hormone-therapy failure. Neuroendocrine cells are non-proliferating and escape apoptotic cell death, although their origin and the causes of their apoptotic resistance have as yet been poorly elucidated. This study demonstrates a new mechanism involved in controlling NED. We report that epidermal growth factor (5-50 ng/ml) promotes neuroendocrine-like differentiation of androgen-independent DU145 prostate cancer cells. This differentiation is associated with an increase in the expression of Neuron Specific Enolase (NSE) and a reduction in cell proliferation and is blocked by inhibiting tyrosine kinase activity with genistein and with compound 56 (C56). An increase in the cAMP level, using dibutryl cAMP (db-cAMP) (1 mM) and isobutylmethylxanthine (100 microM), does not promote NED by itself, but does increase the effect of EGF on NED. In addition, EGF-induced NED protects cells from apoptosis induced with thapsigargin (1 microM) by reducing the thapsigargin-induced cytosolic calcium overload. In order to describe how EGF-induced NED protects cells against thapigargin-induced calcium overload we investigated the spatiotemporal calcium signalling linked to apoptosis. By using thapsigargin in various conditions on DU145 cells and using micro-fluorimetric calcium measurements, we show that depletion of intracellular calcium store induces apoptosis and that the amplitude and duration of the capacitive calcium entry are two apoptosis-modulating parameters. We show that protection against thapsigargin-induced apoptosis conferred by NED is achieved by reducing the amount and the speed of calcium that can be released from calcium pools, as well as modulating the amplitude of the subsequent calcium entry.

Androgens↗
PubMed2001

Ca2+ pools and cell growth. Evidence for sarcoendoplasmic Ca2+-ATPases 2B involvement in human prostate cancer cell growth control.

The present study demonstrates for the first time that intracellular calcium-ATPases and calcium pool content are closely associated with prostate cancer LNCaP cell growth. Cell growth was modulated by changing the amount of epidermal growth factor, serum, and androgene in culture media. Using the microspectrofluorimetric method with Fura-2 and Mag Fura-2 as probes, we show that in these cells, the growth rate is correlated with intracellular calcium pool content. Indeed, an increased growth rate is correlated with an increase in the calcium pool filling state, whereas growth-inhibited cells show a reduced calcium pool load. Using Western blotting and immunocytochemistry, we show that endoplasmic reticulum calcium pump expression is closely linked to LNCaP cell growth, and are a common target of physiological stimuli that control cell growth. Moreover, we clearly demonstrate that inhibition of these pumps, using thapsigargin, inhibits LNCaP cell growth and prevents growth factor from stimulating cell proliferation. Our results thus provide evidence for the essential role of functional endoplasmic reticulum calcium pumps and calcium pool in control of prostate cancer LNCaP cell growth, raising the prospect of new targets for the treatment of prostate cancer.

Blotting, Western↗
PubMed2001

Verapamil inhibits proliferation of LNCaP human prostate cancer cells influencing K+ channel gating.

The mechanisms of verapamil and tetraethylammonium (TEA) inhibition of voltage-gated K+ channels in LNCaP human prostate cancer cells were studied in whole-cell and outside/inside-out patch-clamp configurations. Rapidly activating outward K+ currents (I(K)) exhibited neither C-type, nor rapid (human ether á go-go-related gene-type) inactivation. With 2 mM [Mg(2+)](o), I(K) activation kinetics was independent of holding potential, suggesting the absence of ether á go-go-type K+ channels. Extracellular applications of TEA and verapamil (IC(50) = 11 microM) rapidly (12 s) inhibited I(K) in LNCaP cells. Blocking was also rapidly reversible. Intracellular TEA (1 mM), verapamil (1 mM), and membrane-impermeable N-methyl-verapamil (25 microM) did not influence whole-cell I(K), although both phenylalkylamines inhibited single-channel currents in inside-out patches. Extracellular application of N-methyl-verapamil (25 microM) had no influence on I(K). Our results are compatible with the hypothesis that, in LNCaP cells expressing C-type inactivation-deficient voltage-activated K+ channels, phenylalkylamines interact with an intracellular binding site, and probably an additional hydrophobic binding site that does not bind charged phenylalkylamines. The inhibiting effects of verapamil and TEA on I(K) were additive, suggesting independent K+-channel blocking mechanisms. Indeed, TEA (1 mM) reduced a single-channel conductance (from 7.3 +/- 0.5 to 3.2 +/- 0.4 pA at a membrane potential of +50 mV, n = 6), whereas verapamil (10 microM) reduced an open-channel probability (from 0.45 +/- 0.1 in control to 0.1 +/- 0.09 in verapamil-treated cells, n = 9). The inhibiting effects of verapamil and TEA on LNCaP cell proliferation were not multiplicative, suggesting that both share a common antiproliferative mechanism initiated through a K+ channel block.

Antineoplastic Agents↗
PubMed2001

Effects of hyperprolactinemia on rat prostate growth: evidence of androgeno-dependence.

The effects of the polypeptide hormone prolactin (PRL) in the development and regulation of benign prostate hyperplasia (BPH) and also in prostate cancer are not very well characterized. This study examines the action of PRL, either alone or in association with androgens [testosterone (T) or dihydrotestosterone (DHT)], in the rat prostate gland. The effects of PRL and androgens were investigated after 30 and 60 days in control, castrated, castrated with a substitutive implant of T or DHT, and sham-operated Wistar rats. To enhance PRL release, we induced hyperprolactinemia by administering chronic injections of sulpiride (40 mg. kg(-1). day(-1)). Chronic hyperprolactinemia induces enlargement and inflammation of the lateral rat prostate without any histological changes on ventral and dorsal lobes. We also demonstrate that hyperprolactinemia induces Bcl-2 overexpression in the lateral rat prostate and that this could inhibit the level of apoptosis. The in vivo model established here is a useful in vivo approach for studying the hormonal regulation of normal and pathological prostate development.

Animals↗
PubMed2000

Store depletion and store-operated Ca2+ current in human prostate cancer LNCaP cells: involvement in apoptosis.

1. In the present study, we investigated the mechanisms involved in the induction of apoptosis by the Ca2+-ATPase inhibitor thapsigargin (TG), in androgen-sensitive human prostate cancer LNCaP cells. 2. Exposure of fura-2-loaded LNCaP cells to TG in the presence of extracellular calcium produced an increase in intracellular Ca2+, the first phase of which was associated with depletion of intracellular stores and the second one with consecutive extracellular Ca2+ entry through plasma membrane, store-operated Ca2+ channels (SOCs). 3. For the first time we have identified and characterized the SOC-mediated membrane current (Istore) in prostate cells using whole-cell, cell-attached, and perforated patch-clamp techniques, combined with fura-2 microspectrofluorimetric and Ca2+-imaging measurements. 4. Istore in LNCaP cells lacked voltage-dependent gating and displayed an inwardly rectifying current-voltage relationship. The unitary conductance of SOCs with 80 mM Ca2+ as a charge carrier was estimated at 3.2 +/- 0.4 pS. The channel has a high selectivity for Ca2+ over monovalent cations and is inhibited by Ni2+ (0.5-3 mM) and La3+ (1 microM). 5. Treatment of LNCaP cells with TG (0.1 microM) induced apoptosis as judged from morphological changes. Decreasing extracellular free Ca2+ to 200 nM or adding 0.5 mM Ni2+ enhanced TG-induced apoptosis. 6. The ability of TG to induce apoptosis was not reduced by loading the cells with intracellular Ca2+ chelator (BAPTA-AM). 7. These results indicate that in androgen-sensitive prostate cancer cells the depletion of intracellular Ca2+ stores may trigger apoptosis but that there is no requirement for the activation of store-activated Ca2+ current and sustained Ca2+ entry in induction and development of programmed cell death.

Androgens↗
PubMed1999

[Long-term results of swallowing after horizontal sub-glottic laryngectomy].

This is a retrospective study of 80 patients who have had a horizontal subglottic laryngectomy. The functional results were assessed by means of clinical findings at follow-up and a questionnaire. The mean time to decannulation was 32 days, and to removal of the nasogastric tube 25 days. 45% of patients had no fistula. Of the remaining 55%, there was a false passage for fluids in 90%. These fistulae remained patent for an average of 12 weeks. At one year and beyond, 40% of patients were on a normal diet, 33% were on ground food, 10% on a soft paste diet, 6% on a semi-liquid diet, and 10% were fed by tube. The factors militating towards poor function are age above 65 years, and previous radiotherapy.

Adult↗
PubMed1998

[Eosinophilic meningitis due to Angiostrongylus cantonensis].

Angiostrongylus cantonensis is the most common etiological agent of eosinophilic meningitis. Adults are harbored in the pulmonary arteries of rats. Larvae develop within various natural (mollusks) and paratenic (snails...) hosts. After ingestion, larvae reach the human central nervous system where they cannot complete their life cycle. This zoonosis is usually seen in Southeast Asia and South Pacific islands. Nevertheless, a few imported cases have been reported in Western countries, possible because of the incubation delay. Mild meningeal irritation signs, paresthesia, cranial nerve abnormalities (i.e: II, III, VI, VII) are the most usual by encountered signs. Severe cases with brain involvement have been reported. In endemic areas, typical clinical signs associated with C.S.F. eosinophilic pleocytosis allow the diagnosis but Elisa test may be useful. Prognosis is always excellent even if headache and malaise may last a few weeks. No antihelminthic agent is efficient against Angiostrongylus cantonensis. Prophylaxia by public health counselling program is fruitful.

Angiostrongylus cantonensis↗
PubMed1984

[Aneurysm of the gluteal artery].

A 90 year old man developed the rare lesion of an aneurysm of the gluteal artery, provoked by an injury in a patient with atheromatous multiple aneurysm disease. The inflammatory and permanent nature of the sciatic pain, the history of a recent increase in size of the buttocks, as well as signs of a deglobulization suggest the need for urgent arteriographic exploration for precise definition of the arteries supplying the aneurysm. Surgical treatment is by primary ligature of the hypogastric artery associated with a direct approach in order to perform endoaneurysmorhaphy.

Aged↗
PubMed1976

[Clinical aspects and course of drug-induced upper digestive hemorrhage].

In a series of 500 patients admitted to hospital for upper digestive hemorrhage, the authors studied the influence of taking drugs on the clinical characteristics and course of the original disease. Taking aspirin is exceptional before rupture of esophageal varices. One may isolate a homogenous group of elderly women consuming aspirin and another anti-inflammatory drug, and bleeding from a gastric ulcer. One may also isolate another group of men, bleeding from acute gastro-duodenal lesions after taking aspirin alone. If one considers apart portal hypertension, owing to its extreme gravity, one may note that the prognosis depends on the age. One patient out of five, dies of hemorrhage after the age of 60 years. Taking an anti-inflammatory drug at this age is thus not harmless.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Comparison between oral and systemic antibiotics and their combined use for the prevention of complications in colorectal surgery.

Ninety patients were included in this prospective randomized trial. Each required electric colorectal surgery and was prepared for operation with oral preoperative antibiotic therapy, systemic peroperative therapy, or by a combination of both. The number of each type of septic postoperative complication and their total did not differ between the group treated by oral antibiotics prior to operation and the group treated peroperatively with systemic antibiotic therapy. The total number of septic complications (wall abscesses, fistulas, subdiaphragmatic abscesses, septicemia, peritonitis), however, was significantly less (P less than 0.05) in the group treated by both preoperative oral antibiotics and peroperative systemic antibiotic therapy (3.3 per cent) than in either groups treated only orally preoperatively (30 per cent) or by systemic antibiotic therapy during the operation (23 per cent). The combination of oral antibiotic therapy prior to operation and of systemic peroperative antibiotic therapy, therefore, presents the most effective prophylactic effectiveness.

Administration, Oral↗