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Biomedical subjects

D Langlois

Publications and source records attributed to D Langlois.

At least 55 records · Page 3Linked to original sources
PubMed1989

Insulin-like growth factor-I and insulin increase the stimulatory guanine nucleotide binding protein (Gs) in cultured bovine adrenal cells.

The present study shows that pretreatment of BAC cells with insulin or insulin-like growth factor-I (IGF-I) enhances the cAMP response to maximal concentrations of ACTH and cholera toxin. However, the effects of IGF-I at a nanomolar concentration (50 ng/ml) were higher than for insulin at the same concentration but similar for insulin at a micromolar concentration (10 micrograms/ml). We have investigated whether the effects of the two peptides can be related to some modifications of the guanine nucleotide regulatory binding protein Gs. Insulin enhanced Gs as observed by ADP ribosylation and immunoblotting but the effects were approximately the same at nanomolar and micromolar concentrations; again, the effects of IGF-I (50 ng/ml) were higher. These results indicate that both IGF-I and insulin increase the Gs complex of adenylate cyclase, but IGF-I is more potent than insulin at physiological concentrations.

Adenosine Diphosphate Ribose↗
PubMed1989

[Conservative treatment of breast cancer. Carcinologic and cosmetic results of combination quadrantectomy and irradiation at the Centre Alexis-Vautrin].

We studied the association of quadrantectomy and irradiation in 238 patients with a breast carcinoma treated from 1974 to 1984 in the Alexis-Vautrin Center. Five and ten year survival rate are respectively 89 and 77%. Local relapse rate at five and ten year are 2, and 9%. Local relapse rate is correlated with a young age, a high tumor grade and an internal site of tumor. We studied the cosmetic and functional results and compared objective results according to subjective self-evaluation by the patients.

Adenocarcinoma↗
PubMed1988

Variations in guanine-binding proteins (Gs, Gi) in cultured bovine adrenal cells. Consequences on the effects of phorbol ester and angiotensin II on adrenocorticotropin-induced and cholera-toxin-induced cAMP production.

The corticotropin (ACTH) or cholera-toxin-induced cAMP production by cultured bovine adrenal cells increased progressively between days 0 and 7 of culture. Angiotensin II (A-II), which inhibited both basal and ACTH-stimulated adenylate cyclase of crude adrenal membranes, had no effect on ACTH-induced or cholera-toxin-induced cAMP production by fresh isolated cells (day 0) but progressively potentiated the stimulatory action of both effectors from day 0----1 to day 7 of culture. In contrast, phorbol ester had a potentiating effect on fresh isolated cells. Pretreatment of cells with pertussis toxin enhanced the potentiating effect of A-II on cells between 0 and 3 days of culture, but not after 7 days. ADP-ribosylation by cholera toxin (ribosylating alpha s proteins) or pertussis toxin (alpha i proteins), of adrenal membranes prepared from fresh isolated or cultured cells revealed an increase in alpha s and a dramatic decrease in alpha i, the ratios alpha i/alpha s on days 0, 3 and 7 of culture were 4, 0.6 and 0.1 respectively. These results indicate that (a) A-II had a double effect on ACTH-induced or cholera-toxin-induced cAMP production: one inhibitory mediated by Gi, the other stimulatory mediated by protein kinase C activation; this could explain the lack of apparent effect of A-II on fresh cells; (b) the progressive decrease of alpha i might be responsible for the appearance of the potentiating effect of A-II whereas the progressive increase of alpha s could explain the enhanced responsiveness to ACTH or cholera toxin of cultured cells.

Adenosine Diphosphate Ribose↗
PubMed1988

Vasopressin induces breakdown of phosphoinositides in adrenal tumor Y-1 cells without a steroidogenic effect.

Y-1 adrenal cells contain specific vasopressin (VP) binding sites (27,000 +/- 2,000 sites/cell) of high affinity (KD = 2.2 +/- 0.5 X 10(-9) M). VP which alone has no effect on cAMP production inhibited in a dose-dependent manner (ID50 = 3.5 +/- 0.7 X 10(-11) M) the ACTH-induced cAMP production by Y-1 cells. The inhibitory effect was completely blunted by a 24 h pretreatment of cells with 1 microgram/ml of pertussis toxin. Moreover, VP also stimulated in a dose-dependent manner (ED50 = 2.4 +/- 0.8 X 10(-9) M) the accumulation of inositol phosphates indicating that the VP receptors in Y-1 cells were of the V1 subtype. However, neither VP nor a phorbol ester (4 beta-phorbol 12-myristate 13-acetate, PMA) was able to stimulate Y-1 cell steroidogenesis. Since in a previous work we have shown that Y-1 cells contain high levels of protein kinase C, the present results indicate that the steroidogenic refractoriness of these cells to VP and PMA might involve some step beyond protein kinase C.

Adenylyl Cyclases↗
PubMed1988

Salvage irradiation of oropharynx and mobile tongue about 192 iridium brachytherapy in Centre Alexis Vautrin.

Between 1972 and 1984, 123 patients were treated using 192 Iridium afterloading techniques for recurrence or new cancer of the tongue or oropharynx arising in previously irradiated tissues. The actuarial local control was 67% at 2 years and 59% at 5 years. Local control of the tumor was achieved in the majority of these patients, the actuarial survival was only 48% at 2 years and 24% at 5 years. Twenty-eight patients developed mucosal necrosis. We analyzed prognostic factors for survival, local control, and complication. We proposed a selection for this salvage therapy.

Brachytherapy↗
PubMed1988

Selection of patients for re-irradiation with local implants in carcinomas of oropharynx and tongue.

Between 1972 and 1984, 123 patients with recurrent or new primary carcinomas in previously irradiated areas of soft palate, tonsil, base of tongue or mobile tongue were re-irradiated with iridium-192 afterloading techniques. The average re-irradiation dose was 62 Gy (31-84 Gy) and the total dose 131 Gy (92-162 Gy); only 28 cases of mucosal necrosis were observed (23%). Two and 5 years actuarial local control rates were 67% and 59% and survival rates 48% and 24% respectively. Death was related to local tumor in 48 cases, metastases in 8 cases and intercurrent disease in 39 cases. We analyzed the effect on survival and local control of age, initial tumor site and volume, previous surgery, time between first irradiation and re-irradiation, doses, dose rate, and techniques of brachytherapy. With this analysis as background, we recommend the use of salvage brachytherapy for patients with a) small tumors of soft palate, tonsil or mobile tongue without synchronic lymph node metastases, b) long time interval between first irradiation and re-irradiation, c) new primary tumors (rather than recurrence of first tumor), and d) no previous local surgery. A high re-irradiation dose given with low dose rate is recommended.

Adult↗
PubMed1987

The potentiating effects of phorbol ester on ACTH-, cholera toxin-, and forskolin-induced cAMP production by cultured bovine adrenal cells is not mediated by the inactivation of alpha subunit of Gi protein.

Phorbol ester (PMA) potentiates ACTH-induced cAMP production by both fresh isolated and 7-day-old cultured adrenal cells, but the effect on cultured cells was greater than in fresh cells. In cultured cells the potentiating effects of PMA were dose-dependent and were observed at each effective dose of ACTH without modification of the ED50 for this hormone. These effects of PMA do not seem to be exerted through a modification of the alpha subunit of Gi since pretreatment of the cells with Bordetella pertussis toxin did not modify the action of PMA and since the amount of alpha i in 7-day-old cultured cells was ten times lower than in fresh cells, while the potentiating effect was lower in the latter. Moreover, since PMA still exerted its potentiating action in cells stimulated by maximal concentration of cholera toxin or forskolin either alone or in combination with ACTH, it is likely that its action is not mediated exclusively by the alpha subunit of Gs. Taken together, the present results and those of the literature suggest that this potentiating effect of phorbol ester on effector-induced cAMP production might be mediated by inhibition of the beta-subunit of G proteins.

Adenosine Diphosphate Ribose↗
PubMed1987

Salvage irradiation of oropharyngeal cancers using iridium 192 wire implants: 5-year results of 70 cases.

Between May 1971 and November 1980, 70 patients with recurrent or new oropharyngeal cancers arising in previously irradiated tissues were treated using iridium 192 afterloading techniques. The actuarial local control was 72% at 2 years and 69% at 5 years. Although local control of the tumor was achieved in the majority of these patients, only 10 patients remained alive at 5 years (14%). Patients with lesions of the faucial arch and posterior pharyngeal wall had the best results; local control was achieved in 100% of these patients. Patients with lesions of the base of tongue and of the glosso-tonsillar sulcus had poorer results; local control was achieved in 61%. Because these results compare favorably with the results of previously published series, we recommend re-irradiation with brachytherapy for recurrent or new malignancies arising in a previously irradiated oropharynx. When the lesion is located in the faucial arch, brachytherapy is the treatment of choice. When the lesion is located in the base of tongue, brachytherapy is a reasonable option.

Adult↗
PubMed1987

Angiotensin II (A-II) steroidogenic refractoriness in Y-1 cells in the presence of A-II receptors negatively coupled to adenylate cyclase.

Y1 adrenal tumor cells are resistant to the steroidogenic effect of A-II though they possess specific A-II binding sites. The number of these binding sites is lower in Y1 cells than in bovine adrenal cells, but the affinity is similar in the two models. Moreover, Y1 cells are shown to contain a high level of cytosolic protein kinase C whose properties appear similar to those observed in bovine adrenal cells. However, the activation of protein kinase C by a phorbol ester (PMA) or diacylglycerol (OAG) does not induce steroidogenesis in Y1 cells. On the other hand, A-II, without any effect on adenylate cyclase in basal conditions, reduces the ACTH-induced cAMP production in Y1 cells. This inhibitory effect of A-II is not blocked by phosphodiesterase inhibitor but is completely abolished after 24 hours of pretreatment of intact cells with pertussis toxin. This inhibition is probably mediated by the inhibitory guanine nucleotide regulatory protein (Gi) since the labeled 41 KD-ADP ribosylated protein disappeared after 24 hours of pretreatment of intact cells with pertussis toxin. Moreover, the accumulation of inositol phosphates under A-II stimulation was low, which suggests that the coupling of A-II receptors with phospholipase C is reduced in Y1 cells. The Y1 cell line is probably a good model to study the post membrane events in A-II action.

Adenylate Cyclase Toxin↗
PubMed1987

[Salvage irradiation of epidermoid carcinoma of the oropharynx by iridium 192].

Between May 1971 and March 1982, 73 patients with either recurrent or subsequent squamous cell carcinomas arising in a previously irradiated oropharynx were treated using iridium 192 wires. Although local control was achieved in 72% of these patients, only 10 remained alive at 5 years (14%). Local control was best for tonsillar arch lesions (96%), while base of tongue and glosso-tonsillar sulcus tumors were controlled in only 60%. One of the two patients with a posterior pharyngeal wall lesion is alive and well at 5 years, while the other died of an unknown cause at 20 months. Salvage implantation produced soft tissue necrosis in 36% of base of tongue implants, but only 18% of those involving the tonsillar arch. Although one necrosis was fatal, the others were successfully managed medically. Since these results compare favorably with those of previously published series, we recommend re-irradiation with iridium 192 for recurrent or new malignancies arising in a previously irradiated oropharynx. For tonsillar arch lesions, brachytherapy is the treatment of choice while in the base of tongue, it is reasonable option.

Adult↗
PubMed1985

Reirradiation of head and neck cancers. Presentation of 35 cases treated at the Gustave Roussy Institute.

Thirty-five patients with head and neck carcinoma who were treated with a second course of radiotherapy for relapse or second malignancy at the Gustave Roussy Institute between 1973 and 1981 were studied. Immediate tolerance for total doses greater than 80 Gy was good but 37% of patients suffered from delayed necrosis or bleeding. Thirty-seven per cent of lesions were locally controlled at 3 months and 97% of patients showed a subjective improvement to reirradiation. Local control was obtained in 53% of patients aged between 40 and 60 as compared to 19% in other age groups, and was obtained in 55% of patients who were irradiated a second time with a dose greater than 60 Gy as compared to 8% for doses less than 60 Gy. Complications following treatment are related to failure to achieve local control and area of second treatment fields greater than 70 cm2. Survival was worse for those patients having an interval less than 12 months between the two courses of irradiation and those in whom local control was not achieved.

Adult↗
PubMed1985

Intestinal complications of wide field abdominal irradiation for lymphoma.

We report bowel complications on a series of 32 patients treated with wide field abdominal irradiation for lymphoma between 1979 and 1983. Irradiation was preceded by chemotherapy in 30/32 patients. Fifteen of the 32 patients received total abdominal irradiation and 17/32 received upper hemi-abdominal irradiation to a dose of 20-25 Gy. A boost of 5-20 Gy to a reduced volume was added in 14/32. A special diet was prescribed from the start of irradiation. Immediate tolerance to irradiation was good in 94% of patients. Only five patients developed delayed bowel complications. Definite radiation-induced bowel changes were demonstrated in only two of these cases and other pathology was found to explain the symptomatology in the remaining three. Comparison with a previous series of 50 lymphoma patients treated with total abdominal irradiation to 30 Gy plus inverted Y boost to 10 Gy demonstrated a net improvement in the immediate tolerance and reduction in the incidence and gravity of delayed radiation-related bowel complications in the current series. The reasons for the improved early and late bowel tolerance (radiation dose and volume, etc.) as well as conditions which can mimic late radiation enteritis, will be discussed.

Abdominal Neoplasms↗
PubMed1984

Interstitial radiation therapy for carcinoma of the penis using iridium 192 wires: the Henri Mondor experience (1970-1979).

From 1970 to 1979, a group of 50 patients was treated for squamous cell carcinoma of the penis by interstitial irradiation using an afterloading technique and iridium 192 wires. The group included 9 patients with T1 tumors, 27 with T2 tumors, and 14 with T3 tumors. Forty-five patients presented with no metastatic inguinal nodes (N0), 3 patients with N1 nodes, and 2 patients had N3 nodes. After treatment, 11 patients (1 T1, 6 T2 and 4T3) developed local recurrences; 10 of these 11 patients underwent penile amputation which controlled the tumor in 7 of the patients. One patient refused amputation. Three patients developed post-therapeutic necrosis which necessitated partial amputation in 2 cases. Eight patients developed post-therapeutic urethral stenosis, which required surgical treatment in three of the cases. Overall, at their last follow-up examinations, 74% of the patients were free of disease with conservation of penile morphology and function. Most patients without metastatic nodes (37/45) at diagnosis did not receive prophylatic treatment of the groin. Two of these patients developed delayed metastatic nodes; one was successfully salvaged. All 5 patients presenting with metastatic nodes at diagnosis died, four with uncontrolled regional disease. Twenty-one percent of the patients died of their disease. We advocate interstitial irradiation using iridium 192 wires for the treatment of non-infiltrating or moderately infiltrating squamous cell carcinoma of the penis in which the largest dimension does not exceed 4 cm. Pre-implant circumcision and regular long-term follow-up are necessary. More extensive tumors are better managed surgically. When regular follow-up can be assured, it is reasonable to forgo prophylactic treatment of the inguinal nodes in patients presenting without groin metastasis.

Adult↗
PubMed1984

[Role of iridium-192 endocurietherapy in the treatment of T1 and T2 tumors of the tonsillar region].

From July 1971 to August 1981, 31 selected patients with T1, T2 tumours of the Tonsillar region were treated according to the following protocol: Telecobalt therapy to the primary site and to neck nodes to a dose of 45 Gy, Brachytherapy to the primary site to a dose of 25-30 Gy using iridium 192, Boost dose to involved neck nodes, with electrons, or radical neck dissection, wether N1, N2 or N3. The actuarial survival free of disease is 76% for the whole group and 86% for the NO group. The local control rate is 100% without any recurrences at the primary site having been observed. Disease control in the neck is 94% overall and 100% for the NO group. The effects on salivary function were reduced in comparison with telecobalt therapy alone. These favourable results favour the use of this protocol for superficial, minimally infiltrating tumours less than 4 cm in diameter without obvious extension to the base of the tongue or retromolar trigone.

Adult↗
PubMedDate not supplied

Autocrine regulation of Leydig cell differentiated functions by insulin-like growth factor I and transforming growth factor beta.

The expression and the maintenance of specific differentiated function of Leydig cells are regulated not only by gonadotropin but by locally produced factors, which may act as autocrine regulators. Many factors, in particular growth factors, have been postulated to have such a type of effect on testicular cells, but very few fulfilled the three criteria required to establish a paracrine/autocrine role: (a) presence of receptors and biological action on local cells; (b) local secretion regulated by physiological signals; and (c) blockade of the factor or its receptors must modify the function of local cells. In the present work we demonstrate that two factors, insulin-like growth factor 1 (IGF-I) and transforming growth factor beta1 (TGFbeta1) fulfilled the three criteria: (a) IGF-I stimulates the transcription of the genes encoding Leydig cell differentiated function, leading to an enhanced steroidogenic responsiveness to LH/hCG; (b) Leydig cells (LC) express and secrete IGF-I and this secretion is enhanced by hCG; and (c) incubation of LC with IgG anti-IGF-I, but not with IgG-control, markedly reduced the steroidogenic responsiveness to LH/hCG. In contrast to IGF-I, TGFbeta is a potent inhibitor of LC differentiated function. Moreover, LC express TGFbeta1 mRNA and secrete this peptide. To prove that the locally produced TGFbeta has an autocrine role, LC were transfected with 10 microM of an antisense oligonucleotide (AON) complementary to the translation initiation region of TGFbeta1 mRNA. Transfection with AON but not with sense deoxynucleotide induces a complete disappearance of TGFbeta immunoreactivity in LC and an enhanced hCG-induced testosterone production by LC. This increased steroidogenic responsiveness was associated with a significant enhancement of both LH/hCG receptor mRNA and P450c17 mRNA. Taken together, the above results show that both factors play an autocrine role, although opposite, on Leydig cell function.

Animals↗