A combined cell and growth factor delivery for the repair of a critical size tibia defect using biodegradable hydrogel implants.

The ability to repair critical-sized long-bone injuries using growth factor and cell delivery was investigated using hydrogel biomaterials. Physiological doses of the recombinant human bone morphogenic protein-2 (rhBMP2) were delivered in a sustained manner from a biodegradable hydrogel containing peripheral human blood-derived endothelial progenitor cells (hEPCs). The biodegradable implants made from polyethylene glycol (PEG) and denatured fibrinogen (PEG-fibrinogen, PF) were loaded with 7.

Characterization of Factors Affecting the Detection Limit of EGFR p.T790M in Circulating Tumor DNA.

Objective: Circulating tumor DNA is a promising noninvasive tool for cancer monitoring. One of the challenges in applying this tool is the detection of low-frequency mutations. The detection limit of these mutations varies between different molecular methods.

Mutant Circulating Tumor DNA Is an Accurate Tool for Pancreatic Cancer Monitoring.

Background: Many new pancreatic cancer treatment combinations have been discovered in recent years, yet the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains grim. The advent of new treatments highlights the need for better monitoring tools for treatment response, to allow a timely switch between different therapeutic regimens. Circulating tumor DNA (ctDNA) is a tool for cancer detection and characterization with growing clinical use.

Relationship Between Pityriasis Lichenoides and Mycosis Fungoides: A Clinicopathological, Immunohistochemical, and Molecular Study.

Background: Several cases of pityriasis lichenoides (PL) have been reported to evolve into mycosis fungoides (MF).

Objective: To elucidate clues to this progression.

Methods: Fifty-eight patients with PL between 2000 and 2013 (follow-up: 3-16 years, average: 8.

Clinically significant sub-clonality for common drivers can be detected in 26% of KRAS/EGFR mutated lung adenocarcinomas.

Genetic sub-clonality has been described in multiple malignancies, however the presence of sub-clonality for major drivers in lung adenocarcinoma and its clinical significance is a subject under debate. Using molecular and morphometric approach, 347 lung adenocarcinoma samples were analyzed for KRAS and EGFR sub-clonality, which was further correlated with clinical and pathological variables.KRAS and EGFR mutations were identified in 100 (29%) and 82 (23%) cases, respectively.

Variation in KRAS driver substitution distributions between tumor types is determined by both mutation and natural selection.

Different tumor types vary greatly in their distribution of driver substitutions. Here, we analyzed how mutation and natural selection contribute to differences in the distribution of KRAS driver substitutions between lung, colon and pancreatic adenocarcinomas. We were able to demonstrate that both differences in mutation and differences in selection drive variation in the distribution of KRAS driver substitutions between tumor types.

Subclonality for BRAF Mutation in Papillary Thyroid Carcinoma Is Associated With Earlier Disease Stage.

Context: The presence of driver mutations only in a subset of tumor cells within a single lesion, defined as subclonality, is being appreciated as a clinically significant factor. BRAF mutation is the most common driver mutation in papillary thyroid carcinoma (PTC). There are conflicting data in the literature regarding the presence of BRAF mutation subclonality in PTC and its clinical significance.

Intratumor Heterogeneity of KRAS Mutation Status in Pancreatic Ductal Adenocarcinoma Is Associated With Smaller Lesions.

Objectives: Recent studies have demonstrated intratumor heterogeneity (ITH) for genetic mutations in various tumors and suggest that ITH might have significant clinical impact. Because KRAS is the most commonly mutated oncogene in pancreatic ductal adenocarcinoma and has an important role in pancreatic carcinogenesis, the purpose of this study was to evaluate ITH for KRAS gene mutation and its clinical significance.

Methods: Deep sequencing of 47 pancreatic ductal adenocarcinoma cases was used to determine the fraction of KRAS mutant alleles.

Human blood-derived endothelial progenitor cells augment vasculogenesis and osteogenesis.

Introduction: Endothelial progenitor cells (EPC) participate in angiogenesis and osteogenesis, therefore, have the potential to enhance extra-cortical bone formation.

Aim: To enhance extra-cortical bone formation following local transplantation of human peripheral blood-derived EPC (hEPC) in a guided bone regeneration (GBR) nude rat calvaria model.

Materials And Methods: hEPC were isolated from peripheral blood of healthy volunteers.

Adenoma and carcinoma components in colonic tumors show discordance for KRAS mutation.

Activating mutations in KRAS are common events in the pathogenesis of colorectal carcinoma and predict response to treatment with anti-EGFR antibodies. Molecular pathology testing for KRAS mutations has become the standard of practice for patients with metastatic colorectal carcinoma. Despite the known histologic and molecular differences between adenomas and carcinomas, the concordance of KRAS mutation between adenomas and carcinomas has not been established leaving some open questions regarding the appropriate choice of tissue for KRAS mutation analysis and correct interpretation of the test results.

Mesenchymal stem cells and endothelial progenitor cells stimulate bone regeneration and mineral density.

Background: Alveolar bone deficiency is a major clinical problem in maxillofacial reconstructive surgery. The available surgical techniques to enhance extracortical bone augmentation are generally unpredictable and not satisfying. The aim of the present study is to quantify extracortical bone augmentation and tissue mineral density (TMD) after cotransplantation of peripheral blood-derived endothelial progenitor cells (EPCs) and bone marrow-derived mesenchymal stem cells (MSCs) by microcomputed tomography (micro-CT).

Co-transplantation of endothelial progenitor cells and mesenchymal stem cells promote neovascularization and bone regeneration.

Background: Bone formation relies on sufficient blood supply and osteoprogenitor cells.

Purpose: The study aims to evaluate the influence of endothelial progenitor cells (EPCs) in combination with mesenchymal stem cells (MSCs) on early vascularization and intramembranous bone regeneration.

Materials And Methods: Vertical bone regeneration was tested in rat calvarium guided bone regeneration model.

Peripheral blood-derived endothelial progenitor cells enhance vertical bone formation.

Background: This study presents a novel cell-based approach for extra-cortical bone regeneration.

Objective: To enhance vertical bone formation by combining guided bone regeneration and transplantation of peripheral blood-derived endothelial progenitor cells (EPCs) in a rat calvaria model.

Materials And Methods: EPCs were isolated from peripheral blood of inbred rats.

Mesenchymal stem cells combined with barrier domes enhance vertical bone formation.

Aim: To enhance vertical bone formation in a rat calvarium following combination of guided bone regeneration (GBR) and transplantation of bone marrow derived mesenchymal stem cells (bmMSC).

Materials And Methods: Gold domes (7 mm radius, 5 mm height) were filled with 5 × 10(5) bmMSC or osteogenic transformed bmMSC (otMSC) that were isolated from tibia of inbred rats and mixed with βTCP. Domes filled with βTCP served as control.

Vertical bone augmentation using different osteoconductive scaffolds combined with barrier domes in the rat calvarium.

Purpose: To compare the regenerative potential for vertical bone augmentation of various osteoconductive scaffolds when used in conjunction with barrier domes.

Materials And Methods: Following exposure and perforation of the calvarium, a gold occlusive dome was filled with the tested scaffold and anchored by fixation screws. Flaps were repositioned and secured.

Transplanted blood-derived endothelial progenitor cells (EPC) enhance bridging of sheep tibia critical size defects.

The angiogenic events that accompany bone regeneration function as a "limiting factor" and are the primary regulatory mechanisms that direct the healing process. The general aim of this study was to test whether blood-derived progenitor cells that have endothelial characteristics (EPC), when applied to a large segmental defect, would promote bone regeneration. We established a critical-sized gap platform in sheep tibiae.

Role of bone regeneration and turnover modulators in control of fracture.

Although most fractures heal in accordance with a highly regulated and well-known multistep process, 5%-10% of fractures result in delayed union or nonunion, causing morbidity, prolonged hospitalization, and economic cost for the individual and society. Ongoing research has improved our understanding of genes and molecules that are expressed during fracture healing. This knowledge has been translated into preclinical/clinical trials.

Fracture repair: modulation of fracture-callus and mechanical properties by sequential application of IL-6 following PTH 1-34 or PTH 28-48.

Fracture healing presents a sequence of three major stages: inflammation and granulation tissue formation, callus formation and remodeling. Our working hypothesis was that fracture-repair might be enhanced by stimulating proliferation of chondrocytes and osteoblasts in the early stages of fracture healing followed by sequential acceleration of the remodeling process. In the present study we employed a novel device developed by us implementing a standardized fracture in rat tibiae.

Differential effects of sera from normotensive and hypertensive pregnant women on Ca(2+) metabolism in normal vasular smooth muscle cells.

The clinical features of preeclampsia have been traditionally ascribed to a generalized vascular endothelial cell dysfunction. The present study investigates the effect of sera from preeclamptic women and normal pregnancy on the metabolism of intracellular Ca(2+) concentration ([Ca(2+)](i)) in normal cultured vascular smooth muscle cells (VSMC). Sera were obtained from normotensive pregnant women (NTP) (n = 17), preeclamptic women (PE) (n = 15), pregnant women with chronic (essential) hypertension (pregnant EHT) (n = 8), non-pregnant women with essential hypertension (non-pregnant EHT) (n = 12), and age-matched non-pregnant normotensive women (NNP) (n = 18).