Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts.

Copyright: 2013 Hermann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: In spite of intense research efforts, pancreatic ductal adenocarcinoma remains one of the most deadly malignancies in the world. We and others have previously identified a subpopulation of pancreatic cancer stem cells within the tumor as a critical therapeutic target and additionally shown that the tumor stroma represents not only a restrictive barrier for successful drug delivery, but also serves as a paracrine niche for cancer stem cells. Therefore, we embarked on a large-scale investigation on the effects of combining chemotherapy, hedgehog pathway inhibition, and mTOR inhibition in a preclinical mouse model of pancreatic cancer. EXPERIMENTAL DESIGN: Prospective and randomized testing in a set of almost 200 subcutaneous and orthotopic implanted whole-tissue primary human tumor xenografts. RESULTS: The combined targeting of highly chemoresistant cancer stem cells as well as their more differentiated progenies, together with abrogation of the tumor microenvironment by targeting the stroma and enhancing tissue penetration of the chemotherapeutic agent translated into significantly prolonged survival in preclinical models of human pancreatic cancer. Most pronounced therapeutic effects were observed in gemcitabine-resistant patient-derived tumors. Intriguingly, the proposed triple therapy approach could be further enhanced by using a PEGylated formulation of gemcitabine, which significantly increased its bioavailability and tissue penetration, resulting in a further improved overall outcome. CONCLUSIONS: This multimodal therapeutic strategy should be further explored in the clinical setting as its success may eventually improve the poor prognosis of patients with pancreatic ductal adenocarcinoma

Cervical spine signs and symptoms: perpetuating rather than predisposing factors for temporomandibular disorders in women

AIM: The purpose of this study was to assess in a sample of female community cases the relationship between the increase of percentage of cervical signs and symptoms and the severity of temporomandibular disorders (TMD) and vice-versa. MATERIAL AND METHODS: One hundred women (aged 18-26 years) clinically diagnosed with TMD signs and symptoms and cervical spine disorders were randomly selected from a sample of college students. RESULTS: 43% of the volunteers demonstrated the same severity for TMD and cervical spine disorders (CSD). The increase in TMD signs and symptoms was accompanied by increase in CSD severity, except for pain during palpation of posterior temporal muscle, more frequently observed in the severe CSD group. However, increase in pain during cervical extension, sounds during cervical lateral flexion, and tenderness to palpation of upper fibers of trapezius and suboccipital muscles were observed in association with the progression of TMD severity. CONCLUSION: The increase in cervical symptomatology seems to accompany TMD severity; nonetheless, the inverse was not verified. Such results suggest that cervical spine signs and symptoms could be better recognized as perpetuating rather than predisposing factors for TMD

Mapping Robots to Therapy and Educational Objectives for Children with Autism Spectrum Disorder

The aim of this study was to increase knowledge on therapy and educational objectives professionals work on with children with autism spectrum disorder (ASD) and to identify corresponding state of the art robots. Focus group sessions (n = 9) with ASD professionals (n = 53) from nine organisations were carried out to create an objectives overview, followed by a systematic literature study to identify state of the art robots matching these objectives. Professionals identified many ASD objectives (n = 74) in 9 different domains. State of the art robots addressed 24 of these objectives in 8 domains. Robots can potentially be applied to a large scope of objectives for children with ASD. This objectives overview functions as a base to guide development of robot interventions for these children

Intracellular autofluorescence: a biomarker for epithelial cancer stem cells.

Cancer stem cells (CSCs) are thought to drive tumor growth, metastasis and chemoresistance. Although surface markers such as CD133 and CD44 have been successfully used to isolate CSCs, their expression is not exclusively linked to the CSC phenotype and is prone to environmental alteration. We identified cells with an autofluorescent subcellular compartment that exclusively showed CSC features across different human tumor types. Primary tumor-derived autofluorescent cells did not overlap with side-population (SP) cells, were enriched in sphere culture and during chemotherapy, strongly expressed pluripotency-associated genes, were highly metastatic and showed long-term in vivo tumorigenicity, even at the single-cell level. Autofluorescence was due to riboflavin accumulation in membrane-bounded cytoplasmic structures bearing ATP-dependent ABCG2 transporters. In summary, we identified and characterized an intrinsic autofluorescent phenotype in CSCs of diverse epithelial cancers and used this marker to isolate and characterize these cells

Facilitating a culture of responsible and effective sharing of cancer genome data

Rapid and affordable tumor molecular profiling has led to an explosion of clinical and genomic data poised to enhance the diagnosis, prognostication and treatment of cancer. A critical point has now been reached at which the analysis and storage of annotated clinical and genomic information in unconnected silos will stall the advancement of precision cancer care. Information systems must be harmonized to overcome the multiple technical and logistical barriers to data sharing. Against this backdrop, the Global Alliance for Genomic Health (GA4GH) was established in 2013 to create a common framework that enables responsible, voluntary and secure sharing of clinical and genomic data. This Perspective from the GA4GH Clinical Working Group Cancer Task Team highlights the data-aggregation challenges faced by the field, suggests potential collaborative solutions and describes how GA4GH can catalyze a harmonized data-sharing culture