Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Ann Oncol ; 30(7): 1143-1153, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31081028

RESUMO

BACKGROUND: NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. PATIENTS AND METHODS: Patients' characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497). RESULTS: Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li-Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P < 0.001 for all, with a hazard ratio of 0.681 (95% CI 0.618-0.749) for OS]. CONCLUSION: This nationwide registry of sarcoma patients shows that surgical treatment in a reference center reduces the risk of relapse and death.


Assuntos
Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Sarcoma/mortalidade , Sarcoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Encaminhamento e Consulta/estatística & dados numéricos , Sistema de Registros , Sarcoma/patologia , Procedimentos Cirúrgicos Operatórios/normas , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Taxa de Sobrevida , Adulto Jovem
3.
Eur J Surg Oncol ; 33(6): 735-40, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17400418

RESUMO

AIM: Observe the outcomes after complete simultaneous or delayed resection of synchronous liver metastasis (SLM) from colorectal cancer (CRC). METHODS: From 1994 to 2005, 119 patients were diagnosed with CRC and SLM; 57 patients had simultaneous resection (group I) and 62 patients had staged resection (group II). Perioperative chemotherapy was considered completed if all expected cycle were administrated. RESULTS: Overall survival rates of group I-group II at 1, 3 and 5 years were respectively 91%-93% (p=0,3), 59%-57% (p=0,09) and 32%-25% (p=0,06). The median survival time of group I-group II were respectively 46 months-40 months (p=0,07). There was no statistical difference on survival regarding location of metastasis (p=0,09) or primary tumor location (p=0,2). Patients with simultaneous or staged resection receiving optimal treatment (R0 liver surgery and complete chemotherapy) were respectively 89% and 67% (p=0,04). Twenty three patients developed isolated liver recurrence with higher frequency in staged patients (26% vs 9% p=0,03) without impairment of survival. CONCLUSIONS: Because of postoperative morbidity and prolonged tiring treatment, many patients having staged resection were under treated. However we did not observe statistical difference on survival but we supported that simultaneous resection has to be prefer to achieve an optimal treatment. Lung and bone metastasis are the new challenge for oncologists.


Assuntos
Neoplasias do Colo/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Retais/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/cirurgia , Ablação por Cateter , Quimioterapia Adjuvante , Neoplasias do Colo/patologia , Feminino , Seguimentos , Hepatectomia/métodos , Humanos , Laparotomia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Taxa de Sobrevida
4.
Eur J Surg Oncol ; 32(1): 77-9, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16305820

RESUMO

PURPOSE: To report the long term risks of neoadjuvant chemoradiation (NCRT) after duodenopancreatectomy (DP) for adenocarcinoma of the head of pancreas. METHODS: Between January 1996 and December 2002, 26 patients with biopsy-proven adenocarcinoma of the head of pancreas were treated by this combination of therapies. RESULTS: Two patients had delayed NCRT-related small bowel infarction: one died from superior mesenteric artery stenosis 36 months after DP without recurrence at laparotomy; there was one limited infarction 16 months after DP. CONCLUSIONS: Long term vascular morbidity after NCRT is significant.


Assuntos
Adenocarcinoma/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Antineoplásicos/uso terapêutico , Biópsia , Seguimentos , Humanos , Morbidade , Terapia Neoadjuvante , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Pancreaticoduodenectomia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia
5.
Ann Chir ; 131(8): 431-6, 2006 Oct.
Artigo em Francês | MEDLINE | ID: mdl-16707093

RESUMO

PURPOSE: The aim of this study is to show that the removal of the rectum is not an obstacle to implement an optimal surgery in advanced epithelial cancer of the ovary. MATERIAL AND METHODS: Retrospective study on a population of 44 women with advanced epithelial cancer of the ovary. The surgery was realized between January 95 and July 03, and all surgeries required a posterior exenteration. This treatment was completed by chemotherapy for 36 of them. RESULTS: The median survival of this population is 36.6 months. 6/44 patients (13.6%) had post-operative complications. The completion of chemotherapy started after an average of 5.2 weeks after surgery. All the assessable patients (43/44) have an anal satisfactory continence. CONCLUSION: The posterior exenteration, when it's necessary, for advanced epithelial cancer of the ovary must not be an obstacle to obtain an optimal surgery. Anal continence is respected and there are no more complications. This surgical act is safe for the management of this pathology without delaying the others therapeutics and allowing a satisfactory quality of life.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma Endometrioide/cirurgia , Carcinossarcoma/cirurgia , Colo/cirurgia , Neoplasias Ovarianas/cirurgia , Exenteração Pélvica , Reto/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica , Carcinoma Endometrioide/patologia , Carcinossarcoma/patologia , Colostomia , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Cistectomia , Estudos de Viabilidade , Feminino , Humanos , Histerectomia , Ileostomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Ovário/patologia , Cuidados Pré-Operatórios , Qualidade de Vida , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
6.
Mol Endocrinol ; 7(2): 161-70, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7682286

RESUMO

The D2 dopamine receptor, an inhibitor of adenylyl cyclase, belongs to the family of seven transmembrane domain G-protein-coupled receptors. This receptor is encoded by two mRNAs produced from the same gene by alternative splicing, here referred to as D2L and D2S. The resultant proteins are identical except for an insertion of 29 amino acids in the putative third intracytoplasmic domain. This domain has been shown to be important for the coupling of this family of receptors to G-proteins. We have previously shown that there is differential inhibition of the adenylyl cyclase activity when these two receptors are produced in JEG3 cells; D2S is more efficient than D2L. To understand the molecular basis of such differential activity, we analyzed the G-proteins expressed in these cells. Here we show that G alpha i2 is absent in this cell line. Moreover, it is possible to restore the same inhibitory activity obtained by D2S when an expression vector encoding this alpha-subunit is cotransfected with D2L. In addition, transfections of the two receptors in a recipient cell line containing the three G alpha i subtypes confirm that the two receptors behave similarly. We conclude that the 29-amino acid insertion present in D2L allows it to interact specifically with G alpha i2. These data suggest that in vivo the function of activated D2 receptors is exerted by specific interactions with Gi-protein subtypes.


Assuntos
Inibidores de Adenilil Ciclases , Dopamina/farmacologia , Proteínas de Ligação ao GTP/metabolismo , Receptores Dopaminérgicos/metabolismo , Transdução de Sinais , 1-Metil-3-Isobutilxantina/farmacologia , Colforsina/farmacologia , Humanos , Splicing de RNA , RNA Mensageiro/metabolismo , Receptores Dopaminérgicos/classificação , Receptores Dopaminérgicos/genética , Espiperona/metabolismo , Transfecção , Células Tumorais Cultivadas
7.
Ann Chir ; 130(9): 562-5, 2005 Oct.
Artigo em Francês | MEDLINE | ID: mdl-16202886

RESUMO

OBJECTIVE: Assessing impact of major liver resection (LR) for hepatic metastasis of colorectal cancer (HMCC) on post operative courses and long term survival in the elderly. PATIENTS AND METHOD: Thirty-three consecutive patients aged over 70 years-old were treated in our institution for up to 3 resectable metachronous HMCC. Fifteen patients had major LR (9 right hepatectomy, 3 extended right hepatectomy, 3 left hepatectomy) without pre or postoperative chemotherapy (group 1) and 18 patients were exclusively treated by chemotherapy (group 2) because of high ASA score (ASA 3) or patients refusal. RESULTS: No patients died of another cause that colorectal cancer disease during observation time. All patients of group 2 died during observation time. Post operative mortality and morbidity of group 1 were respectively 0% and 33%. Survival at 1 and 2 years of group 1-2 were respectively 73-50% (P=0,04) and 47-15% (P=0,05). Median survival of group 1 and 2 were respectively 22 and 12 months (P=0,03). CONCLUSIONS: Major LR for HMCC could be proposed regardless the age. High ASA score, multiple (more than 4) metastasis location, evolutive disease could justify an exclusive medical approach.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Morbidade , Prognóstico , Análise de Sobrevida
8.
Neuropharmacology ; 35(11): 1595-604, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9025107

RESUMO

The influence of intracellular pH (pHi) changes on the formation of inositol phosphate metabolites (IPs) produced by glutamatergic stimulation was studied in 8-day-old rat brain synaptoneurosomes. For this purpose pHi was measured using 2',7'-bis-(2-carboxyl)-5,6-carboxyfluorescein (BCECF) fluorimetric assay in parallel with the basal and receptor-mediated formations of inositol monophosphate (IP1) and inositol bisphosphate (IP2). We found that glutamate (1 mM), which induces a transient acidification (delta pH = -0.05), produces an identical accumulation of IP1 and IP2. K+ (30 mM), which provokes an alkalinization of the internal medium (delta pH = +0.22), mainly leads to the formation of IP1 metabolites. Paired combinations of glutamate with 1, 5 and 10 mM NH4+ finally result in an alkalinization of the intrasynaptoneurosomal medium. These combinations produce a strong decrease of the IP2 level concomitant with an increase of the IP1 formation, compared to the levels of IP1 and IP2 evoked by glutamate alone. The total amount of IPs (IP1 + IP2) produced by these combinations is not different from that obtained with glutamate alone. Paired combinations of carbachol with NH4+ produce an identical alkalinization to that produced by NH4+ alone. These combinations produce an increased IP1 accumulation, while the IP2 formation is slightly decreased. When the internal medium is acidified by diminishing the external concentration of Na+, the ratio IP1/IP2 produced after metabotropic glutamate receptor (mGluR) activation is shifted to lower values, while it is not affected for the muscarinic stimulation. These data suggest that the mGluR-associated pathway in synaptoneurosomes is sensitive to pHi shifts, while the muscarinic receptor-associated pathway is less altered when pHi is manipulated. It may be proposed that pH-sensitive inositol phosphate dephosphorylating systems, i.e. phosphatases, are associated with mGluRs in this preparation.


Assuntos
Ácido Glutâmico/farmacologia , Fosfatidilinositóis/metabolismo , Sinaptossomos/metabolismo , Animais , Química Encefálica/efeitos dos fármacos , Química Encefálica/fisiologia , Carbacol/farmacologia , Corantes Fluorescentes , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Agonistas Muscarínicos/farmacologia , Prosencéfalo/efeitos dos fármacos , Prosencéfalo/metabolismo , Compostos de Amônio Quaternário/farmacologia , Ratos , Receptores de Glutamato Metabotrópico/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/metabolismo
9.
Biochem Pharmacol ; 39(12): 1913-9, 1990 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-2353934

RESUMO

Various neuroactive substances, including excitatory and inhibitory amino acids, biogenic amines and neuropeptides, were tested for their ability to stimulate the inositol phosphate (IPs) cascade in the presence of lithium in the rat cochlea. Among them, only the muscarinic agonists (carbachol and oxotremorine M) were able to stimulate the IPs formation in 12-day-old rat cochleas. The carbachol-elicited IPs formation was inhibited by muscarinic antagonists with the following relative order of potency: atropine greater than 4-DAMP much greater than pirenzepine greater than methoctramine = AF-DX 116. This pharmacological profile suggests that the activation of the M3 muscarinic receptor subtype is responsible for the increase in IPs synthesis in the rat cochlea. However, an interaction with a m5 receptor subtype could not be completely excluded. The unusual link of only one receptor subtype with the phosphoinositide breakdown in the cochlea, as opposed to the usual existence of several receptors coupled to this transduction system in other organs such as the brain, suggest a unique role for muscarinic agonists in the cochlea.


Assuntos
Cóclea/metabolismo , Fosfatos de Inositol/metabolismo , Receptores Muscarínicos/metabolismo , Animais , Carbacol/farmacologia , Células Cultivadas , Cóclea/efeitos dos fármacos , Inositol/metabolismo , Lítio/farmacologia , Oxotremorina/farmacologia , Ratos , Ratos Endogâmicos , Receptores Muscarínicos/efeitos dos fármacos , Trítio
10.
Neurochem Int ; 21(2): 229-35, 1992 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1363865

RESUMO

Dithiotreitol (DTT), a sulfhydryl reducing agent inhibits in a dose-dependent manner the inositol phosphates (IPs) accumulation responses evoked by glutamate and potassium without affecting that of carbachol in rat forebrain synaptoneurosomes. Furthermore, DTT neither provokes a depolarization of the membrane, nor increases the internal calcium concentration. Depolarization and internal calcium rise are known to stimulate IPs production. Moreover, DTT does not modify the depolarizing effect and the calcium rise elicited by glutamate and potassium. In addition, the antioxidant compounds 2-aminoethylisothiouronium bromide (AET) and ascorbic acid have no effect on the basal and stimulated IPs accumulation. Thus, it is concluded that: (1) two distinct transduction pathways exist, one stimulated by glutamate and depolarizing agents and the other one by cholinergic agonists; (2) DTT produces its inhibition by reducing disulfide bridges likely at the level of proteins of the phosphoinositide transduction mechanism.


Assuntos
Cálcio/metabolismo , Carbacol/farmacologia , Ditiotreitol/farmacologia , Glutamatos/farmacologia , Fosfatos de Inositol/metabolismo , Potássio/farmacologia , Prosencéfalo/metabolismo , Sinaptossomos/metabolismo , Animais , Antioxidantes/farmacologia , Fura-2 , Ácido Glutâmico , Inositol/metabolismo , Cinética , Potenciais da Membrana/efeitos dos fármacos , Ratos , Espectrometria de Fluorescência , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/fisiologia
11.
Neurochem Int ; 13(4): 463-7, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-20501304

RESUMO

Inositol phosphate synthesis elicited by excitatory amino acids was measured in rat forebrain synaptoneurosomes in presence of Li(+). Quisqualate (QA) was the most potent excitatory amino acid inducing inositol phosphate formation. This QA action was not blocked by any of the usual antagonists [glutamate-amino-methyl-sulphonate (GAMS); glutamate-diethyl-ester (GDEE); ?-d-glutamyl-glycine (?-DGG)] known to inhibit the QA-induced depolarization. The same was found for the most potent and selective QA antagonist reported so far [6-nitro-7-cyanoquinoxaline-2,3-dion (FG 9065)]. In addition, dl-?-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) a potent depolarizing agonist at the quisqualate receptor subtype was about 300 times less potent than quisqualate in increasing inositol phosphate accumulation. Our results provide the first pharmacological evidence indicating that a new quisqualate receptor subtype, tentatively termed sAA(2) is responsible for inositol phosphate formation.

12.
Neurochem Int ; 29(4): 371-81, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8939445

RESUMO

Calcium ions (Cd2+) inhibit inositol phosphate (IP) formation elicited by glutamate (GLU) or K+ ions, without affecting carbachol (Carb)-induced IP response in 8-day-old rat forebrain synaptoneurosomes and synaptosomes. On the contrary, Cd2+ was almost ineffective in blocking GLU- and K(+)-responses in hippocampal neurones in culture. The mechanism of Cd2+ inhibition was thus examined in synaptoneurosomes. Extensive washing of synaptoneurosomes pretreated for 1, 5, 15, or 30 min by 100 microM Cd2+ did not modify the inhibitory effect of Cd2+ on GLU-, K(+)- and A23187-evoked IP formation or its lack of effect on Carb response. The later addition of a high affinity Cd2+ chelator (100 microM), N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) also did not reverse the inhibitory effect. TPEN, however, penetrates into synaptoneurosomes and efficiently displaces Cd2+ from the Fura-2-Cd2+ complex as shown by Fura-2 fluorescence recordings. TPEN is not easily removed from the intracellular space, as demonstrated by its ability to still block Cd(2+)-induced Fura-2 fluorescence increase after extensive washing. Pretreatment of synaptoneurosomes by this chelator did not prevent Cd2+ inhibition of GLU-induced IP formation. These data indicate that Cd2+ ions rapidly, irreversibly and extracellularly inhibit GLU-elicited IP formation in synaptoneurosomes or synaptosomes, but not in hippocampal neurones in culture. It is speculated that Cd2+ ions could allow one to distinguish the activity of presynaptic metabotropic glutamate receptors (mGLURs) linked to phosphoinositide metabolism from that of mGLURs located postsynaptically.


Assuntos
Cádmio/farmacologia , Terminações Pré-Sinápticas/metabolismo , Receptores de Glutamato/metabolismo , Fosfolipases Tipo C/metabolismo , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Calcimicina/farmacologia , Ácido Glutâmico/farmacologia , Hipocampo/citologia , Hipocampo/metabolismo , Potássio/farmacologia , Ácido Quisquálico/farmacologia , Ratos , Sinaptossomos/metabolismo
13.
J Clin Pathol ; 57(11): 1215-8, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15509688

RESUMO

Gastric duplication cyst (GDC) in an adult can have several clinical presentations. A review of the literature showed previously reported cases of GDC presenting as pancreatic pseudocyst or with greatly raised concentrations of carbohydrate antigen 19-9 (CA 19-9). It is often difficult to discriminate GDC from pancreatic cystic tumour, in particular pancreatic mucinous cystadenoma, in which concentrations of carcinoembryonic antigen and CA 19-9 are classically raised. This report describes an adult case of GDC mimicking a mucinous cystadenoma of the pancreas. This is the first report of a simultaneous increase in carcinoembryonic antigen and CA 19-9 in GDC in the absence of malignancy. Although few cases of carcinoma arising from a GDC having been reported, the production of oncofetal antigens raises the problem of a precancerous condition in long standing intestinal duplications. In this situation surgical resection must be performed.


Assuntos
Cistadenoma Mucinoso/diagnóstico , Cistos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Gastropatias/diagnóstico , Estômago/anormalidades , Adulto , Cistos/congênito , Cistos/patologia , Diagnóstico Diferencial , Epitélio/patologia , Feminino , Humanos , Gastropatias/congênito , Gastropatias/patologia , Tomografia Computadorizada por Raios X
14.
Int J Dev Neurosci ; 7(3): 257-66, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2569258

RESUMO

The evolution of excitatory amino acids-(EAA) stimulated inositol phosphates (IPs) turnover during postnatal development was investigated in synaptoneurosomes prepared from rat forebrains. The two main EAA agonists which induce the IPs synthesis were quisqualate (QA) and N-methyl-D-aspartate (NMDA). The QA and NMDA stimulations of IPs formation present a particular developmental pattern, characterized by an active phase during rat synaptogenesis. The QA-evoked IPs accumulation peaked in synaptoneurosomes prepared from 8-day-old rat forebrains while that evoked by NMDA peaked in synaptoneurosomes from 12-day-old rats. These two developmental patterns are specific of the EAA agonists since the other various neuroactive substances tested (carbachol (Carb), noradrenaline, and high concentrations of potassium) induced an IPs accumulation, which increases during development and reaches a maximum in synaptoneurosomes of adult animals. Aging leads to a decrease in the capability of EAAs and muscarinic agonists to stimulate IPs formation in synaptoneurosomes, whereas the stimulation of IPs turnover by noradrenaline remains constant. Taken together, these results suggest that EAAs play a key role during brain development by sequentially activating two receptor subtypes, a new QA receptor, and a NMDA receptor, linked to the phosphoinositide metabolism. They may also indicate that these EAA-induced IPs responses are related to neuronal plastic events, the amplitude of which decreases with aging.


Assuntos
Envelhecimento/metabolismo , Ácido Aspártico/análogos & derivados , Lobo Frontal/metabolismo , Glutamatos/farmacologia , Fosfatos de Inositol/metabolismo , Oxidiazóis/farmacologia , Fosfatos Açúcares/metabolismo , Animais , Ácido Aspártico/farmacologia , Carbacol/farmacologia , Feminino , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/crescimento & desenvolvimento , Ácido Glutâmico , Masculino , N-Metilaspartato , Norepinefrina/farmacologia , Ácido Quisquálico , Ratos , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo
15.
Neurosci Lett ; 98(2): 222-8, 1989 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-2565568

RESUMO

K+, excitatory amino acids (EAAs) and carbachol (Carb) were tested separately or in pairs for their ability to stimulate inositol phosphate (IPs) formation in rat forebrain synaptoneurosomes. K+ ions per se, stimulate IPs synthesis (158% of the control value) as well as EAAs and Carb. The glutamate (Glu)- and quisqualate (QA)-elicited IPs formation is not additive with that evoked by K+. Inversely, K+ ions (up to 30 mM) potentiate the Carb-induced IPs accumulation. These results indicate that QA (or Glu) and Carb enhance IPs formation independently and that QA- and K+ -induced IPs responses are interdependent. This suggests that they share a 'common intermediate' step in the multistep mechanism which leads from receptor activation to the IPs synthesis. This 'common intermediate' step may be depolarization and/or Na+ influx.


Assuntos
Aminoácidos/farmacologia , Carbacol/farmacologia , Lobo Frontal/metabolismo , Fosfatos de Inositol/metabolismo , Potássio/farmacologia , Fosfatos Açúcares/metabolismo , Sinaptossomos/metabolismo , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/farmacologia , Química Encefálica/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Glutamatos/farmacologia , Ácido Glutâmico , N-Metilaspartato , Oxidiazóis/farmacologia , Ácido Quisquálico , Ratos
16.
J Gastrointest Surg ; 8(4): 502-10, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15120377

RESUMO

Resection of localized pancreatic head ductal adenocarcinoma (LPHDA) has a limited impact on survival. Mechanisms of improvement provided by preoperative chemoradiation therapy (CRT) remain under debate. This study analyzes the outcome of patients treated for LPHDA to delineate the benefits of CRT. Among 87 patients with LPHDA, 17 had a pancreaticoduodenectomy alone (group I). Thirty-nine with initially resectable cancers received CRT with 5-fluorouracil-based chemotherapy (group II). Thirty-one with initially unresectable cancers were similarly treated by CRT (group III). Patients in groups II and III were restaged after completion of CRT. In patients with resectable disease, resection was planned. Patients in groups I and II were statistically comparable in terms of age, sex, and pretherapeutic stage. Median survival and 2-year overall survival in group I were 13.7 months and 31%, respectively. In group II, 23 patients (59%) had a pancreaticoduodenectomy (group IIa) and 16 patients (41%) did not have resection (group IIb). Median survival and 2-year overall survival were as follows: group IIa, 26.6 months and 51%; and group IIb, 6.1 months and 0%, respectively. In group IIa, pathologic examination revealed eight major responses (35%) including two sterilized specimens, and none of the patients had locoregional recurrence. In group III, none of the patients had resection, and median survival was 8 months with one 2-year survivor. Patient selection appears to play a major role with regard to results achieved with preoperative CRT followed by pancreaticoduodenectomy. However, a high histologic response rate and excellent local control can also be achieved.


Assuntos
Carcinoma Ductal Pancreático/radioterapia , Neoplasias Pancreáticas/radioterapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Cuidados Pré-Operatórios , Taxa de Sobrevida , Fatores de Tempo
17.
Toxicol Lett ; 51(3): 331-8, 1990 May.
Artigo em Inglês | MEDLINE | ID: mdl-2160140

RESUMO

Neomycin (an aminoglycoside antibiotic), ethacrynate (a loop diuretic), cisplatin (an anticancer drug) and mercuric chloride are chemically unrelated drugs which present similar ototoxic and nephrotoxic properties. We have found that all these molecules inhibit inositol phosphate turnover induced by carbachol or glutamate in rat brain synaptoneurosomes. Since this second messenger system appears to be a key mechanism for cell functioning and even survival, our observations raise the possibility that the expression of the specific toxicity of these compounds may result from excessive inhibition of the phosphoinositide cascade.


Assuntos
Encéfalo/metabolismo , Cisplatino/toxicidade , Ácido Etacrínico/toxicidade , Fosfatos de Inositol/metabolismo , Cloreto de Mercúrio/toxicidade , Neomicina/toxicidade , Sinaptossomos/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Carbacol/antagonistas & inibidores , Carbacol/farmacologia , Antagonistas de Aminoácidos Excitatórios , Glutamatos/farmacologia , Fosfatidilinositóis/metabolismo , Ratos , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Sinaptossomos/efeitos dos fármacos
18.
Hear Res ; 47(3): 229-34, 1990 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-2228806

RESUMO

The age related-intensity developmental pattern of the phosphoinositide breakdown, which leads to the formation of intracellular second messengers, was investigated in rat cochleas by measuring the accumulation of inositol phosphates induced by carbachol in the presence of LiCl. The accumulation of the phosphoinositide metabolites elicited by this muscarinic agonist is very low at post-natal day 1 and particularly large during the period between post-natal days 8 and 14 with a peak around day 12. In the 25-day-old rat cochlea, carbachol induced a 2-fold increase in inositol phosphates (IPs) accumulation, with respect to the basal control level. The apparent affinities of the carbachol-induced IPs responses are 49.6, 31.6 and 36.7 microM in cochleas of 12-, 16- and 25-day-old rats, respectively, thus suggesting that the specific developmental changes are rather due to a modification in the number of muscarinic cholinergic receptors than to alterations of the apparent affinity of carbachol for its receptors. This developmental pattern of carbachol-elicited IPs accumulation reveals a striking time coincidence with both the efferent synaptogenesis at the outer hair cells (OHCs) level and the period of increased sensitivity of OHCs to aminoglycoside toxicity. Phosphoinositide breakdown may, consequently, play a role in the maturation of OHCs and their efferent supply. In addition, the remaining IPs response measured at 25 post-natal days indicates that muscarinic agonist-mediated IPs metabolism also occurs in mature cochlea, and might be involved in the regulation of OHCs motility.


Assuntos
Envelhecimento/metabolismo , Carbacol/farmacologia , Cóclea/metabolismo , Fosfatos de Inositol/biossíntese , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Animais Recém-Nascidos/metabolismo , Cóclea/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Concentração Osmolar , Ratos , Ratos Endogâmicos
19.
Endosc Ultrasound ; 2(3): 148-52, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24949383

RESUMO

OBJECTIVE: Endoscopic ultrasound (EUS) is established as the most accurate technique for pre-operative locoregional staging of gastroesophageal junction (GEJ) adenocarcinoma, the purpose of the present study was to evaluate the distant lymph nodes (LNs) EUS-fine-needle aspiration (FNA) impact in therapeutic decision for patients with GEJ adenocarcinoma. MATERIALS AND METHODS: Retrospective study was made, with cross-sectional, non-probabilistic analysis from prospectively collected database for all GEJ adenocarcinoma staging patients referred between January 2009 and August 2012 in Paoli-Calmette Institute in Marseille-France. RESULTS: A total of 154 patients with GEJ adenocarcinoma were managed in our institution, of whom 113 (73.3%) had non-distant metastatic disease at computed tomography (CT) scan and underwent EUS for initial tumor staging prior to a treatment decision. On A total of 113 patients undergoing EUS, 8 (7%) patients underwent endoscopic resection and 6 (5.3%) underwent direct surgical resection. Of the remaining 99 patients (87.6%), 24 (21.2%) distant LN EUS-FNA were made. Seventeen LN had EUS malignant features, including 9 (52.9%) that were confirmed as malignant and underwent palliative treatment with chemotherapy. Ninety (79.6%) patients were treated with pre-operative neoadjuvant therapy and were revaluated after. 4 (4.4%) had metastatic disease at CT scan (underwent palliative treatment) and 65 (72.2%) underwent EUS restaging to treatment decision revaluation. Of these, twelve (18.4%) distant LN EUS-FNA were performed. Seven had LN EUS malignancy features, including 4 (57.1%) that were confirmed as malignant and underwent palliative treatment. The remaining 61 patients underwent surgery. As stated above, 21 patients (23.3%) did not undergo EUS restaging, including 10 (47.6%) that did not go to surgery because patient's age, poor general status and comorbidities, 6 (28.5%) had a loss of follow-up, 1 (4.7%) underwent to surgery due to chemotherapy collateral effects, 3 (14.2%) were still on pre-operative chemotherapy and 1 (4.7%) died for sepsis after mediastinal EUS-FNA, this was the only complication event evidenced. EUS-FNA changed clinical management in 54.2% of patients who met the criteria inclusion (distant LN with malignancies EUS features), which corresponds to 11.5% of patients with GEJ adenocarcinoma. CONCLUSION: EUS-FNA was able to provide a different tumor staging and these differences were associated with treatment received. EUS-FNA had a significant impact on treatment decision.

20.
Clin Res Hepatol Gastroenterol ; 36(4): 371-7, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22361442

RESUMO

UNLABELLED: Endoscopic resection (EMR) and radiofrequency ablation (RFA) form part of the treatment of Barrett's oesophagus (BO), dysplasia, superficial adenocarcinoma (OAC) associated with BO. PATIENTS AND METHODS: Between June 2008 and April 2011, 34 patients underwent treatment with RFA (HALO system(®)), in a tertiary centre. For the study, patients were divided into two groups. Group 1 (16 patients of average 60 years old; 14 men, two women) received EMR and RFA. Group 2 (18 patients averaging 59 years age; 14 men, four women) received RFA without EMR in the year preceding the RFA. RESULTS: In group 1, high grade dysplasia (HGD) was eradicated in 12 cases (92%), low grade dysplasia (LGD) in three cases (100%). Complete response occurred in nine cases (56%), partial response in 100% of cases. Mean follow-up was 15 months. In group 2, HGD was eradicated in one patient (100%), LGD in three patients (64%). A complete response was achieved in eight patients, partial response in four cases (77%). Mean follow-up was 10 months. The complication rate for groups 1 and 2 was of 18% and 10% respectively. No complication prevented completion of treatment or continued monitoring. Recurrence was evaluated to 5% in both groups. CONCLUSION: RFA associated with EMR is feasible, offering probably better results and a very important advantage: a more complete histology before follow-up. Our results show effective treatment of BO and associated dysplasia with a low rate of complication. Nevertheless, when new techniques of BO ablation are used, the need to obtain histology before treatment should not be forgotten.


Assuntos
Esôfago de Barrett/cirurgia , Ablação por Cateter , Esofagoscopia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA