Identification of novel vascular targets in lung cancer

Background: Lung cancer remains the leading cause of cancer-related death, largely owing to the lack of effective treatments. A tumour vascular targeting strategy presents an attractive alternative; however, the molecular signature of the vasculature in lung cancer is poorly explored. This work aimed to identify novel tumour vascular targets in lung cancer. Methods: Enzymatic digestion of fresh tissue followed by endothelial capture with Ulex lectin-coated magnetic beads was used to isolate the endothelium from fresh tumour specimens of lung cancer patients. Endothelial isolates from the healthy and tumour lung tissue were subjected to whole human genome expression profiling using microarray technology. Results: Bioinformatics analysis identified tumour endothelial expression of angiogenic factors, matrix metalloproteases and cellsurface transmembrane proteins. Predicted novel tumour vascular targets were verified by RNA-seq, quantitative real-time PCR analysis and immunohistochemistry. Further detailed expression profiling of STEAP1 on 82 lung cancer patients confirmed STEAP1 as a novel target in the tumour vasculature. Functional analysis of STEAP1 using siRNA silencing implicates a role in endothelial cell migration and tube formation. Conclusions: The identification of cell-surface tumour endothelial markers in lung is of interest in therapeutic antibody and vaccine development

Endocrine regulation of predator-induced phenotypic plasticity

Elucidating the developmental and genetic control of phenotypic plasticity remains a central agenda in evolutionary ecology. Here, we investigate the physiological regulation of phenotypic plasticity induced by another organism, specifically predator-induced phenotypic plasticity in the model ecological and evolutionary organism Daphnia pulex. Our research centres on using molecular tools to test among alternative mechanisms of developmental control tied to hormone titres, receptors and their timing in the life cycle. First, we synthesize detail about predator-induced defenses and the physiological regulation of arthropod somatic growth and morphology, leading to a clear prediction that morphological defences are regulated by juvenile hormone and life-history plasticity by ecdysone and juvenile hormone. We then show how a small network of genes can differentiate phenotype expression between the two primary developmental control pathways in arthropods: juvenoid and ecdysteroid hormone signalling. Then, by applying an experimental gradient of predation risk, we show dose-dependent gene expression linking predator-induced plasticity to the juvenoid hormone pathway. Our data support three conclusions: (1) the juvenoid signalling pathway regulates predator-induced phenotypic plasticity; (2) the hormone titre (ligand), rather than receptor, regulates predator-induced developmental plasticity; (3) evolution has favoured the harnessing of a major, highly conserved endocrine pathway in arthropod development to regulate the response to cues about changing environments (risk) from another organism (predator)

Intrathoracic Esophagogastric Anastomosis Using a Linear Stapler Following Minimally Invasive Esophagectomy in the Prone Position

[Background] Minimally invasive esophagectomy (MIE) in the prone position typically includes thoracoscopic mediastinal dissection and laparoscopic gastric tube construction, followed by esophagogastric anastomosis in the neck. We introduced an intrathoracic esophagogastric anastomosis using linear staplers. [Technique] The lower mediastinal dissection and the gastric tube construction are done in the laparoscopic part of the operation. The esophagus is transected at the cranial level of the aortic arch after the completion of the upper mediastinal lymph node dissection in the prone position. The excess length of the gastric tube is sacrificed before making the anastomosis. Side-to-side esophagogastric anastomosis is performed using a 35-mm endoscopic linear stapler. The entry hole is closed with hand suturing using the posterior and the axillary port. [Results] Twenty-six patients with middle or lower esophageal tumor underwent MIE with an intrathoracic anastomosis. The mean thoracoscopic procedure time was 302 min. One patient had an anastomotic leakage, which was successfully managed with drainage. There has been no anastomotic stenosis. Pneumonia was observed in two patients. There was no mortality. [Conclusions] MIE with an intrathoracic linear-stapled anastomosis with the patient in the prone position is safe and feasible

Esofagectomia trans-hiatal versus transtorácica: experiência do Instituto Nacional do Câncer (INCA)

OBJETIVO: Analisar comparativamente a morbimortalidade e sobrevida após esofagectomia trans-hiatal (TH) ou transtorácica (TT). METODOS: Estudo retrospectivo não randomizado de 68 pacientes com neoplasia de esôfago operados no INCA entre 1997 e 2005, divididos em dois grupos: 1 - TH (33 pacientes); e 2 - TT (35 pacientes). RESULTADOS: A idade média foi 40,7 anos (25 - 74 anos), sendo 73,5% homens. Tumores do 1/3 médio predominaram no Grupo 2 (48,6% versus 21,2%, p = 0,02). A média de linfonodos dissecados foi maior no Grupo 2 (21,6 versus 17,8 linfonodos, p = 0,04), porém sem diferença no número de linfonodos metastáticos (4,1 versus 3,9 linfonodos, p = 0,85). O tempo cirúrgico médio foi maior no Grupo 2 (410 versus 270 minutos, p = 0,001). O tempo médio de internação também foi maior no Grupo 2 (19 versus 14 dias, p = 0,001). A morbidade operatória foi 50%, sem diferença significativa (42,4% versus 57,1%, p = 0,23). Fístula esofágica ocorreu em 13,2%, sem diferença significativa (9,1% versus 17,1%, p = 0,23). A mortalidade foi 5,8% (04 pacientes), sem diferença significativa (1,4% versus 4,4%, p = 0,83). CONCLUSÃO: Neste estudo, a morbimortalidade não apresentou diferença em relação à via de acesso para a esofagectomia, apesar do maior tempo cirúrgico e de permanência hospitalar na via TT. A sobrevida global em 3 e 5 anos também foi maior na TT, possivelmente devido a maior freqüência de estágios iniciais em pacientes submetidos à transtorácica