RESUMO
The 20th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Saskatoon, Saskatchewan, 28-29 September 2018. This interactive multidisciplinary conference is attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancers. In addition, invited speakers from other provinces participate. Surgical, medical, and radiation oncologists, and allied health care professionals participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancers.
Assuntos
Neoplasias Gastrointestinais , Guias de Prática Clínica como Assunto , Biomarcadores Tumorais , Consenso , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/radioterapia , Neoplasias Gastrointestinais/cirurgia , Neoplasias Gastrointestinais/terapia , Humanos , Hipertermia Induzida , Terapia NeoadjuvanteRESUMO
The objective of the present study was to compare the ability of experimental and commercial xylanases to degrade, in vitro, the arabinoxylan (AX) fraction in digesta from 28-d-old piglets fed a wheat (Triticum aestivum)-based diet (49% wheat). Pigs were euthanized at 1, 2, 3, or 4 h after feeding; stomach and ileum contents were isolated and frozen and later used for the in vitro studies. Xylan solubilization provided information regarding the ability of the enzymes to degrade AX during the harsh in vivo conditions prevailing in the gastrointestinal tract. The hydrolytic capacity of a commercial xylanase was compared with that of an experimental xylanase using stomach digesta (pH 1.8) obtained at 4 h after feeding. Relative to the control, both enzymes increased (P < 0.001) xylan solubilization 3-fold. In the ileal digesta (1 h), xylan solubilization was increased by 36% (P < 0.001). Inclusion of arabinofuranosidases (Ara f) with xylanases increased xylan solubilization in stomach samples (P = 0. 007 and P = 0. 030) but not in ileal samples (P = 0.873 and P = 0.997). Our results illustrate clearly the importance of using different conditions and substrates when enzyme performance is studied in vitro as a prescreening tool for setting up in vivo trials.
Assuntos
Ração Animal/análise , Dieta/veterinária , Grão Comestível/classificação , Conteúdo Gastrointestinal/química , Suínos/fisiologia , Xilanos/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Triticum , Xilosidases/classificação , Xilosidases/metabolismoRESUMO
BACKGROUND: Choledochal cyst resection and hepaticojejunostomy have historically been performed using an open technique. We describe here the largest single experience with this procedure using laparoscopic techniques in eight consecutive pediatric patients. METHODS: There were six girls and two boys, of ages ranging from 3 months to 13 years. All had type I choledochal cysts. Three were asymptomatic, having been noted on prenatal ultrasonography. Five ports were utilized: one 5-mm telescope port at the umbilicus, two 3-mm operating ports on both sides of the umbilicus, one 5-mm left subcostal port for liver retraction, and one LLQ 5-mm assistant port. RESULTS: The median operating time was 155 min (range 110-250 min), with one conversion to an open procedure due to a high transection of the cyst leading to partial retraction of the left hepatic duct into the liver substance. Mean hospital stay was 3 days. At a mean follow-up of 18.8 months, all patients were anicteric and asymptomatic. CONCLUSIONS: Laparoscopic resection of choledochal cysts can be performed safely in pediatric patients with minimal morbidity and good long-term results.
Assuntos
Cisto do Colédoco/cirurgia , Laparoscopia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Jejunostomia/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Tempo de Internação , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
The efficacy of glatiramer acetate in multiple sclerosis (MS) is thought to involve the production of Th2 regulatory lymphocytes that secrete anti-inflammatory cytokines; however, other mechanisms cannot be excluded Given that activated T lymphocytes infiltrate into the CNS and become in dose proximity to microglia, we evaluated whether glatiramer acetate affects the potential interaction between T cells and microglia. We report that the co-culture of activated T lymphocytes with microglia led to the induction of several cytokines, and that these were reduced by glatiramer acetate treatment Morphological transformation of bipolar/ramified microglia into an activated ameboid form was attenuated by glatiramer acetate. These results reveal a novel mechanism for glatiramer acetate: the impairment of activated T cells to effectively interact with microglia to produce cytokines. The net result of a non-inflammatory milieu within the CNS, in spite of T cell infiltration, may help account for the amelioration of disease activity in MS patients on glatiramer acetate therapy.
Assuntos
Comunicação Celular/efeitos dos fármacos , Imunossupressores/farmacologia , Microglia/citologia , Esclerose Múltipla/tratamento farmacológico , Peptídeos/farmacologia , Linfócitos T/citologia , Adulto , Adesão Celular/efeitos dos fármacos , Adesão Celular/imunologia , Comunicação Celular/imunologia , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Acetato de Glatiramer , Humanos , Macrófagos/citologia , Esclerose Múltipla/imunologia , Linfócitos T/metabolismoRESUMO
The SH2 domain-containing SHP-1 tyrosine phosphatase has been shown to negatively regulate a broad spectrum of growth factor- and cytokine-driven mitogenic signaling pathways. Included among these is the cascade of intracellular events evoked by stem cell factor binding to c-Kit, a tyrosine kinase receptor which associates with and is dephosphorylated by SHP-1. Using a series of glutathione S-transferase (GST) fusion proteins containing either tyrosine-phosphorylated segments of the c-Kit cytosolic region or the SH2 domains of SHP-1, we have shown that SHP-1 interacts with c-Kit by binding selectively to the phosphorylated c-Kit juxtamembrane region and that the association of c-Kit with the larger of the two SHP-1 isoforms may be mediated through either the N-terminal or C-terminal SHP-1 SH2 domain. The results of binding assays with mutagenized GST-Kit juxtamembrane fusion proteins and competitive inhibition assays with phosphopeptides encompassing each c-Kit juxtamembrane region identified the tyrosine residue at position 569 as the major site for binding of SHP-1 to c-Kit and suggested that tyrosine 567 contributes to, but is not required for, this interaction. By analysis of Ba/F3 cells retrovirally transduced to express c-Kit receptors, phenylalanine substitution of c-Kit tyrosine residue 569 was shown to be associated with disruption of c-Kit-SHP-1 binding and induction of hyperproliferative responses to stem cell factor. Although phenylalanine substitution of c-Kit tyrosine residue 567 in the Ba/F3-c-Kit cells did not alter SHP-1 binding to c-Kit, the capacity of a second c-Kit-binding tyrosine phosphatase, SHP-2, to associate with c-Kit was markedly reduced, and the cells again showed hyperproliferative responses to stem cell factor. These data therefore identify SHP-1 binding to tyrosine 569 on c-Kit as an interaction pivotal to SHP-1 inhibitory effects on c-Kit signaling, but they indicate as well that cytosolic protein tyrosine phosphatases other than SHP-1 may also negatively regulate the coupling of c-Kit engagement to proliferation.