The vascular endothelium and shear stress are critical determinants of physiological hemostasis and platelet function in vivo, yet current diagnostic and monitoring devices do not fully incorporate endothelial function under flow in their assessment and, therefore, they can be unreliable and inaccurate. It is challenging to include the endothelium in assays for clinical laboratories or point-of-care settings because living cell cultures are not sufficiently robust. Here, we describe a microfluidic device that is lined by a human endothelium that is chemically fixed, but still retains its ability to modulate hemostasis under continuous flow in vitro even after few days of storage. This device lined with a fixed endothelium supports formation of platelet-rich thrombi in the presence of physiological shear, similar to a living arterial vessel. We demonstrate the potential clinical value of this device by showing that thrombus formation and platelet function can be measured within minutes using a small volume (0.5 mL) of whole blood taken from subjects receiving antiplatelet medications. The inclusion of a fixed endothelial microvessel will lead to biomimetic analytical devices that can potentially be used for diagnostics and point-of-care applications.Electronic supplementary materialThe online version of this article (doi:10.1007/s10544-016-0095-6) contains supplementary material, which is available to authorized users.

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Purpose: Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients, there are no options for targeted therapy, and existing treatments are limited by toxicity. The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot feasibility trial aiming to prospectively generate patient-derived organoids (PDO) from patients with PDAC and test their drug sensitivity and correlation with clinical outcomes. Experimental Design: PDOs were established from a heterogeneous population of patients with PDAC including both basal and classical PDAC subtypes. Results: A method for classifying PDOs as sensitive or resistant to chemotherapy regimens was developed to predict the clinical outcome of patients. Drug sensitivity testing on PDOs correlated with clinical responses to treatment in individual patients. Conclusions: These data support the investigation of PDOs to guide treatment in prospective interventional trials in PDAC.

Increased prevalence of AI in normal-appearing epithelium is associated with breast cancer and increased breast cancer risk. The increased prevalence may reflect dysregulation, even in normal-appearing epithelium, of genomic processes contributing to cancer development. The clinical significance of genetic alterations in the subset of controls remains to be determined.

Background: CDKN1C (also known as p57 KIP2 ) is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21 CIP1 and B/p27 KIP1 ) have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo.

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Quantitative AI/LOH fingerprinting is a potentially valuable tool to improve diagnosis and optimize treatment for the growing number of second breast malignancies.

We evaluated the potential utility of occult circulating tumor DNA as a molecular marker of disease in subjects previously diagnosed with breast cancer. Using 24 microsatellite markers located at sites of frequent loss of heterozygosity (LOH) or allele imbalance in breast cancer, we analyzed DNA from 16 primary tumors (Stage IIA or more advanced) and 30 longitudinally collected plasma specimens. Clinical data at the time of plasma collection were obtained. All 16 tumors were characterized by an individual pattern of LOH. LOH was detected in 12 of 30 (40%) plasma samples, taken from 8 of 14 (57%) subjects. However, the number of LOH in plasma was small (n ‫؍‬ 15), and the mean proportion of LOH was much lower than in the tumors (0.05 vs. 0.52). Although infrequent, 12 of 15 (80%) plasma LOH were concordant with abnormalities in the paired tumors, and the mean percent LOH was higher than in normal plasmas, suggesting that they were authentic tumor-derived abnormalities. We found, despite this, no association, between plasma LOH and tumor stage or clinical status at time of blood collection (i.e., LOH was as common in subjects with no evident disease as in those with evident disease). In addition, detection of LOH was not consistent between serial samples from 5 of 11 subjects (45%), despite stable clinical conditions. No association with clinical outcome was evident, although the sample size was small. Microsatellite instability in plasma was infrequent, nonconcordant with paired tumor and inconsistent in serial samples. This pilot study suggests that identifying tumor-specific LOH in the plasma of breast cancer subjects may not be useful for detecting occult metastases or for monitoring disease. Other detection techniques may be more promising, but circulating tumor DNA may not be a sufficiently accurate reflection of breast cancer clinical status or tumor activity.