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1.  Enhancing Orientation and Mobility Skills in Learners who are Blind through Video gaming 
In this work we present the results of the cognitive impact evaluation regarding the use of Audiopolis, an audio and/or haptic-based videogame. The software has been designed, developed and evaluated for the purpose of developing orientation and mobility (O&M) skills in blind users. The videogame was evaluated through cognitive tasks performed by a sample of 12 learners. The results demonstrated that the use of Audiopolis had a positive impact on the development and use of O&M skills in school-aged blind learners.
PMCID: PMC4259253  PMID: 25505797
Haptic and Audio Interfaces; Orientation; Mobility; People Who Are Blind; H.5.m. Information interfaces and presentation (e.g., HCI): Miscellaneous; Human Factors
2.  Audio Haptic Videogaming for Developing Wayfinding Skills in Learners Who are Blind 
Interactive digital technologies are currently being developed as a novel tool for education and skill development. Audiopolis is an audio and haptic based videogame designed for developing orientation and mobility (O&M) skills in people who are blind. We have evaluated the cognitive impact of videogame play on O&M skills by assessing performance on a series of behavioral tasks carried out in both indoor and outdoor virtual spaces. Our results demonstrate that the use of Audiopolis had a positive impact on the development and use of O&M skills in school-aged learners who are blind. The impact of audio and haptic information on learning is also discussed.
PMCID: PMC4254778  PMID: 25485312
Haptic and Audio Interfaces; Orientation; Mobility; Navigation; People Who Are Blind; H.5.m. Information interfaces and presentation (e.g., HCI); Miscellaneous; Human Factors; Design; Measurement
3.  Endothelial cell-derived interleukin-6 regulates tumor growth 
BMC Cancer  2014;14:99.
Endothelial cells play a complex role in the pathobiology of cancer. This role is not limited to the making of blood vessels to allow for influx of oxygen and nutrients required for the high metabolic demands of tumor cells. Indeed, it has been recently shown that tumor-associated endothelial cells secrete molecules that enhance tumor cell survival and cancer stem cell self-renewal. The hypothesis underlying this work is that specific disruption of endothelial cell-initiated signaling inhibits tumor growth.
Conditioned medium from primary human dermal microvascular endothelial cells (HDMEC) stably transduced with silencing RNA for IL-6 (or controls) was used to evaluate the role of endothelial-derived IL-6 on the activation of key signaling pathways in tumor cells. In addition, these endothelial cells were co-transplanted with tumor cells into immunodefficient mice to determine the impact of endothelial cell-derived IL-6 on tumor growth and angiogenesis.
We observed that tumor cells adjacent to blood vessels show strong phosphorylation of STAT3, a key mediator of tumor progression. In search for a possible mechanism for the activation of the STAT3 signaling pathway, we observed that silencing interleukin (IL)-6 in tumor-associated endothelial cells inhibited STAT3 phosphorylation in tumor cells. Notably, tumors vascularized with IL-6-silenced endothelial cells showed lower intratumoral microvessel density, lower tumor cell proliferation, and slower growth than tumors vascularized with control endothelial cells.
Collectively, these results demonstrate that IL-6 secreted by endothelial cells enhance tumor growth, and suggest that cancer patients might benefit from targeted approaches that block signaling events initiated by endothelial cells.
PMCID: PMC4016552  PMID: 24533454
Cervical Cancer; Signaling pathways; Molecular targeted therapy; STAT3
4.  Endothelial derived factors inhibit anoikis of head and neck cancer stem cells 
Oral Oncology  2011;48(1):26-32.
Recent evidence demonstrated that cancer stem cells reside in close proximity to blood vessels in human head and neck squamous cell carcinomas (HNSCC). These findings suggest the existence of a supporting perivascular niche for cancer stem cells.
The purpose of this study was to evaluate the effect of endothelial cell-secreted factors on the behavior of head and neck cancer stem-like cells (HNCSC).
Materials and methods
HNCSC were identified by sorting UM-SCC-22A (cell line derived from a primary squamous cell carcinoma of the oropharynx) and UM-SCC-22B (derived from the metastatic lymph node of the same patient) for CD44 expression and ALDH (aldehyde dehydrogenase) activity. HNCSC (ALDH+CD44+) and control (ALDH−CD44−) cells were cultured in ultra-low attachment plates in presence of conditioned medium from primary human endothelial cells.
ALDH+CD44+ generated more orospheres than control cells when cultured in suspension. The growth factor milieu secreted by endothelial cells protected HNCSC against anoikis. Mechanistic studies revealed that endothelial cell-secreted vascular endothelial growth factor (VEGF) induces proliferation of HNCSC derived from primary UM-SCC-22A, but not from the metastatic UM-SCC-22B. Likewise, blockade of VEGF abrogated endothelial cell-induced Akt phosphorylation in HNCSC derived from UM-SCC-22A while it had a modest effect in Akt phosphorylation in HNCSC from UM-SCC-22B.
This study revealed that endothelial cells initiate a crosstalk that protect head and neck cancer stem cells against anoikis, and suggest that therapeutic interference with this crosstalk might be beneficial for patients with head and neck cancer.
PMCID: PMC3261237  PMID: 22014666
Head and neck squamous cell carcinoma; Perivascular niche; Angiogenesis; Tumor microenvironment; Metastasis
5.  Metronomic small molecule inhibitor of Bcl-2 (TW-37) is anti-angiogenic and potentiates the anti-tumor effect of ionizing radiation 
To investigate the effect of a metronomic (low dose, high frequency) small molecule inhibitor of Bcl-2 (TW-37) in combination with radiotherapy on microvascular endothelial cells in vitro and in tumor angiogenesis in vivo.
Methods and materials
Primary human dermal microvascular endothelial cells (HDMEC) were exposed to ionizing radiation and/or TW-37, and colony formation as well as capillary sprouting in 3-D collagen matrices, was evaluated. Xenografts vascularized with human blood vessels were engineered by co-transplantation of human squamous cell carcinoma cells (OSCC3) and HDMEC seeded in highly porous biodegradable scaffolds into the subcutaneous space of immunodeficient mice. Mice were treated with metronomic TW-37 and/or radiation, and tumor growth was evaluated.
Low dose TW-37 sensitized primary endothelial cells to radiation-induced inhibition of colony formation. Low dose TW-37 or radiation partially inhibited endothelial cell sprout formation, while in combination these therapies abrogated new sprouting. Combination of metronomic TW-37 and low dose radiation inhibited tumor growth and resulted in significant increase in time to failure as compared to controls, whereas single agents did not. Notably, histopathological analysis revealed that tumors treated with TW-37 (with or without radiation) are more differentiated and showed more cohesive invasive fronts, which is consistent with less aggressive phenotype.
These results demonstrate that metronomic TW-37 potentiates the anti-tumor effects of radiotherapy, and suggest that patients with head and neck cancer might benefit from the combination of small molecule inhibitor of Bcl-2 and radiation therapy.
PMCID: PMC2946486  PMID: 20675079
Developmental therapeutics; Radiotherapy; Head and Neck Cancer; Apoptosis; Neovascularization
6.  HOXB5 expression in oral squamous cell carcinoma 
Journal of Applied Oral Science  2011;19(2):125-129.
Human HOX genes encode transcription factors that act as master regulators of embryonic development. They are important in several processes such as cellular morphogenesis and differentiation. The HOXB5 gene in particular has been reported in some types of neoplasm, but not in oral cancer.
The present study investigated the expression of HOXB5 in oral squamous cell carcinoma (SCC) and in non-tumoral adjacent tissues, focusing on verifying its possible role as a broad tumor-associated gene and its association with histopathological and clinical (TNM) characteristics.
Material and Methods
RT-PCR was performed to amplify HOXB5 mRNA in 15 OSCCs and adjacent non-tumoral epithelium. A possible association with TNM and histopathologic data was verified by the chi-square and post-hoc t-test.
HOXB5 was amplified in 60% non-tumoral epithelium and in 93.3% carcinomas. No statistically significant differences were found regarding the HOXB5 mRNA expression and TNM or histological grade.
HOXB5 is expressed in OSCCs and its role in cancer progression should be further investigated.
PMCID: PMC4243750  PMID: 21552713
Genes, homeobox; Carcinoma, squamous cell; Gene expression; RT-PCR, neoplasm staging

Results 1-6 (6)