beta1-integrin mediates myelin-associated glycoprotein signaling in neuronal growth cones

Several myelin-associated factors that inhibit axon growth of mature neurons, including Nogo66, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), can associate with a common GPI-linked protein Nogo-66 receptor (NgR). Accumulating evidence suggests that myelin inhibitors also signal through unknown NgR-independent mechanisms. Here we show that MAG, a RGD tri-peptide containing protein, forms a complex with β1-integrin to mediate axonal growth cone turning responses of several neuronal types. Mutations that alter the RGD motif in MAG or inhibition of β1-integrin function, but not removal of NgRs, abolish these MAG-dependent events. In contrast, OMgp-induced repulsion is not affected by inhibition of b1-integrin function. We further show that MAG stimulates tyrosine phosphorylation of focal adhesion kinase (FAK), which in turn is required for MAG-induced growth cone turning. These studies identify β1-integrin as a specific mediator for MAG in growth cone turning responses, acting through FAK activation.     

Peptic ulcer and gastric carcinoma: diagnosis with biphasic radiography compared with fiberoptic endoscopy

The diagnostic value of biphasic radiographic examination of the stomach and duodenum was compared with that of fiberoptic endoscopy in a prospective, blinded study of 385 patients with dyspepsia. This investigation was directed at gastric malignancies and peptic ulcers. Methodologically there is no absolute standard for a study of this kind because histologic examination is useful for detection of cancer but inadequate for ulcers. As an alternative, kappa indexes and the sensitivity and specificity, as derived by Hui and Walter, were calculated and compared. For the detection of gastric carcinoma, radiographic and endoscopic findings had almost perfect agreement beyond chance. For gastric ulcers, radiography and endoscopy had substantial agreement, which became perfect if small ulcers (less than 5 mm) were excluded. For duodenal ulcers, radiography had a lower sensitivity than endoscopy; this disagreement disappeared if small ulcers were excluded. Both methods have equal merit; choice of the initial diagnostic procedure will therefore depend on cost, discomfort to the patient, and risk of complications.     

Improving outcomes in geriatric surgery: Is there more to the equation?

The era of geriatric surgery has arrived with increased global life expectancy. The need to optimize outcomes in this group of patients goes beyond traditional outcomes such as postoperative morbidity and mortality indicators. Recognizing risk factors that impact adverse surgical outcomes such as frailty and sarcopenia, individualizing optimization strategies such as prehabilitation and a multidisciplinary geriatric surgical service have been shown to improve postoperative outcomes and help the older surgical patient regain premorbid function and maintain quality of life. There needs to be a concerted effort to increase awareness of this increasingly important topic in practicing surgeons around the world to meet the challenges of the aging population.     

Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients

Recent research advances show that tumor cell intravasation (entry into the circulation) and metastasis occur very early in breast cancer progression. Clinical studies also illustrate the potential importance of detection of circulating tumor cells (CTCs) in outcomes of patients with metastatic breast cancer. Whether these cells exhibit the invasiveness and express tumor stem or progenitor markers, hallmark of the metastatic phenotype, is less well characterized. To detect CTCs with the invasive phenotype and to explore their molecular features, we applied a functional cell separation method, called collagen adhesion matrix (CAM) assay, as enrichment and identification steps. The CAM‐coated device successfully recovered tumor cells spiked in 1 ml of blood with a 54% ± 9% (n = 18) recovery rate and 0.5–35% purity, and detected invasive tumor cells in 10/10 blood samples (100% yield) from patients with metastatic breast cancer with a range of 18–256 CTCs/ml and average of 126 ± 25 (mean ± SD) CTCs/ml. CTCs were detected in blood samples of 28/54 (52%) Stage I–III breast cancer patients with a mean count of 61 CTCs/ml. Furthermore, the relative frequency of these cells correlated to the staging, lymph node‐status and survival of patients with early stage breast cancer. CAM‐captured cells were capable of propagation in culture. Gene expression and multiplex flow cytometric analyses on CAM‐captured cells demonstrated the existence of distinct populations of CTCs including these of epithelial lineage and stem or progenitor cells. Thus, CAM‐initiated CTC detection provides advantages for examining invasiveness and tumor progenitor phenotypes.