Pulmonary squamous cell carcinoma following head and neck squamous cell carcinoma: Metastasis or second primary?

NARCIS (Netherlands)

Geurts, Tom W.; Nederlof, Petra M.; van den Brekel, Michiel W. M.; van't Veer, Laura J.; de Jong, Daphne; Hart, August A. M.; van Zandwijk, Nico; Klomp, Houke; Balm, Alfons J. M.; van Velthuysen, Marie-Louise F.

2005-01-01

Purpose: To distinguish a metastasis from a second primary tumor in patients with a history of head and neck squamous cell carcinoma and subsequent pulmonary squamous cell carcinoma. Experimental Design: For 44 patients with a primary squamous cell carcinoma of the head and neck followed by a

Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

Science.gov (United States)

2018-04-10

Squamous Cell Carcinoma of the Oropharynx; Squamous Cell Carcinoma of the Larynx; Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Hypopharynx; Squamous Cell Carcinoma of the Paranasal Sinus; Head and Neck Squamous Cell Carcinoma; Squamous Cell Cancer; Head and Neck Carcinoma

Clinicopathological characteristics of head and neck Merkel cell carcinomas.

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Knopf, Andreas; Bas, Murat; Hofauer, Benedikt; Mansour, Naglaa; Stark, Thomas

2017-01-01

There are still controversies about the therapeutic strategies and subsequent outcome in head and neck Merkel cell carcinoma. Clinicopathological data of 23 Merkel cell carcinomas, 93 cutaneous head and neck squamous cell carcinomas (HNSCCs), 126 malignant melanomas, and 91 primary parotid gland carcinomas were comprehensively analyzed. Merkel cell carcinomas were cytokeratin 20 (CK20)/neuron-specific enolase (NSE)/chromogranin A (CgA)/synaptophysin (Syn)/thyroid transcription factor-1 (TTF-1)/MIB1 immunostained. All Merkel cell carcinomas underwent wide local excision. Parotidectomy/neck dissection was performed in 40%/33% cutaneous Merkel cell carcinoma and 100%/100% in parotid gland Merkel cell carcinoma. Five-year recurrence-free interval (RFI)/overall survival (OS) was significantly higher in malignant melanoma (81/80%) than in cutaneous Merkel cell carcinoma/HNSCC. Interestingly, 5-year RFI/OS was significantly higher in Merkel cell carcinoma (61%/79%) than in HNSCC (33%/65%; p Merkel cell carcinoma and parotid gland carcinomas, nor in the immunohistochemical profile. Five-year RFI/OS was significantly better in cutaneous Merkel cell carcinoma when compared with TNM classification matched HNSCC. Five-year RFI/OS was comparable in parotid gland Merkel cell carcinoma and other primary parotid gland malignancies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 92-97, 2017. © 2016 Wiley Periodicals, Inc.

Using strategic movement to calibrate a neural compass: a spiking network for tracking head direction in rats and robots.

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Peter Stratton

Full Text Available The head direction (HD system in mammals contains neurons that fire to represent the direction the animal is facing in its environment. The ability of these cells to reliably track head direction even after the removal of external sensory cues implies that the HD system is calibrated to function effectively using just internal (proprioceptive and vestibular inputs. Rat pups and other infant mammals display stereotypical warm-up movements prior to locomotion in novel environments, and similar warm-up movements are seen in adult mammals with certain brain lesion-induced motor impairments. In this study we propose that synaptic learning mechanisms, in conjunction with appropriate movement strategies based on warm-up movements, can calibrate the HD system so that it functions effectively even in darkness. To examine the link between physical embodiment and neural control, and to determine that the system is robust to real-world phenomena, we implemented the synaptic mechanisms in a spiking neural network and tested it on a mobile robot platform. Results show that the combination of the synaptic learning mechanisms and warm-up movements are able to reliably calibrate the HD system so that it accurately tracks real-world head direction, and that calibration breaks down in systematic ways if certain movements are omitted. This work confirms that targeted, embodied behaviour can be used to calibrate neural systems, demonstrates that 'grounding' of modelled biological processes in the real world can reveal underlying functional principles (supporting the importance of robotics to biology, and proposes a functional role for stereotypical behaviours seen in infant mammals and those animals with certain motor deficits. We conjecture that these calibration principles may extend to the calibration of other neural systems involved in motion tracking and the representation of space, such as grid cells in entorhinal cortex.

Using strategic movement to calibrate a neural compass: a spiking network for tracking head direction in rats and robots.

Science.gov (United States)

Stratton, Peter; Milford, Michael; Wyeth, Gordon; Wiles, Janet

2011-01-01

The head direction (HD) system in mammals contains neurons that fire to represent the direction the animal is facing in its environment. The ability of these cells to reliably track head direction even after the removal of external sensory cues implies that the HD system is calibrated to function effectively using just internal (proprioceptive and vestibular) inputs. Rat pups and other infant mammals display stereotypical warm-up movements prior to locomotion in novel environments, and similar warm-up movements are seen in adult mammals with certain brain lesion-induced motor impairments. In this study we propose that synaptic learning mechanisms, in conjunction with appropriate movement strategies based on warm-up movements, can calibrate the HD system so that it functions effectively even in darkness. To examine the link between physical embodiment and neural control, and to determine that the system is robust to real-world phenomena, we implemented the synaptic mechanisms in a spiking neural network and tested it on a mobile robot platform. Results show that the combination of the synaptic learning mechanisms and warm-up movements are able to reliably calibrate the HD system so that it accurately tracks real-world head direction, and that calibration breaks down in systematic ways if certain movements are omitted. This work confirms that targeted, embodied behaviour can be used to calibrate neural systems, demonstrates that 'grounding' of modelled biological processes in the real world can reveal underlying functional principles (supporting the importance of robotics to biology), and proposes a functional role for stereotypical behaviours seen in infant mammals and those animals with certain motor deficits. We conjecture that these calibration principles may extend to the calibration of other neural systems involved in motion tracking and the representation of space, such as grid cells in entorhinal cortex.

Head tilt produced by hemilabyrinthectomy does not depend on the direct vestibulospinal tracts.

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Fukushima, K; Fukushima, J; Kato, M

1988-01-01

Head tilt is one of the most characteristic and enduring symptoms produced by hemilabyrinthectomy and is compensated by the central nervous system with time. In order to study the central mechanisms of compensation of the head tilt, it is first necessary to understand how it is produced. However, its mechanism remains unknown. Experiments were performed in cats to examine whether the direct vestibulocollic pathways are responsible for the head tilt, as suggested by some authors. Hemilabyrinthectomies produced a characteristic head tilt in cats in which the medial and/or one lateral vestibulospinal tracts (VSTs) had been interrupted. The lesions of the medial VST did not influence the preexisting head tilt produced by hemilabyrinthectomies. These results suggest that the head tilt produced by hemilabyrinthectomies does not depend on the activity of the VSTs.

Self-Adaptive Correction of Heading Direction in Stair Climbing for Tracked Mobile Robots Using Visual Servoing Approach

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Ji, Peng; Song, Aiguo; Song, Zimo; Liu, Yuqing; Jiang, Guohua; Zhao, Guopu

2017-02-01

In this paper, we describe a heading direction correction algorithm for a tracked mobile robot. To save hardware resources as far as possible, the mobile robot’s wrist camera is used as the only sensor, which is rotated to face stairs. An ensemble heading deviation detector is proposed to help the mobile robot correct its heading direction. To improve the generalization ability, a multi-scale Gabor filter is used to process the input image previously. Final deviation result is acquired by applying the majority vote strategy on all the classifiers’ results. The experimental results show that our detector is able to enable the mobile robot to correct its heading direction adaptively while it is climbing the stairs.

Stem cell treatment for avascular necrosis of the femoral head: current perspectives

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Houdek MT

2014-04-01

Full Text Available Matthew T Houdek,1 Cody C Wyles,2 John R Martin,1 Rafael J Sierra11Department of Orthopedic Surgery, 2School of Medicine, Mayo Clinic, Rochester, MN, USAAbstract: Avascular necrosis (AVN of the femoral head is a progressive disease that predominantly affects younger patients. Although the exact pathophysiology of AVN has yet to be elucidated, the disease is characterized by a vascular insult to the blood supply of the femoral head, which can lead to collapse of the femoral head and subsequent degenerative changes. If AVN is diagnosed in the early stages of the disease, it may be possible to attempt surgical procedures which preserve the hip joint, including decompression of the femoral head augmented with concentrated bone marrow. The use of autologous stem cells has shown promise in halting the progression of AVN of the femoral head, and subsequently preventing young patients from undergoing total hip arthroplasty. The purpose of this study was to review the current use of stem cells for the treatment of AVN of the femoral head.Keywords: avascular necrosis, femoral head, osteonecrosis, stem cells, concentrated bone marrow

Anticancer activity of drug conjugates in head and neck cancer cells.

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Majumdar, Debatosh; Rahman, Mohammad Aminur; Chen, Zhuo Georgia; Shin, Dong M

2016-06-01

Sexually transmitted oral cancer/head and neck cancer is increasing rapidly. Human papilloma virus (HPV) is playing a role in the pathogenesis of a subset of squamous cell carcinoma of head and neck (SCCHN). Paclitaxel is a widely used anticancer drug for breast, ovarian, testicular, cervical, non-small cell lung, head and neck cancer. However, it is water insoluble and orally inactive. We report the synthesis of water soluble nanosize conjugates of paclitaxel, branched PEG, and EGFR-targeting peptide by employing native chemical ligation. We performed a native chemical ligation between the N-hydroxy succinimide (NHS) ester of paclitaxel succinate and cysteine at pH 6.5 to give the cysteine-conjugated paclitaxel derivative. The thiol functionality of cysteine was activated and subsequently conjugated to multiarm thiol-PEG to obtain the paclitaxel branched PEG conjugate. Finally, we conjugated an EGFR-targeting peptide to obtain conjugates of paclitaxel, branched PEG, and EGFR-targeting peptide. These conjugates show anticancer activity against squamous cell carcinoma of head and neck cells (SCCHN, Tu212).

Genetic alterations in head and neck squamous cell carcinomas

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Nagai M.A.

1999-01-01

Full Text Available The genetic alterations observed in head and neck cancer are mainly due to oncogene activation (gain of function mutations and tumor suppressor gene inactivation (loss of function mutations, leading to deregulation of cell proliferation and death. These genetic alterations include gene amplification and overexpression of oncogenes such as myc, erbB-2, EGFR and cyclinD1 and mutations, deletions and hypermethylation leading to p16 and TP53 tumor suppressor gene inactivation. In addition, loss of heterozygosity in several chromosomal regions is frequently observed, suggesting that other tumor suppressor genes not yet identified could be involved in the tumorigenic process of head and neck cancers. The exact temporal sequence of the genetic alterations during head and neck squamous cell carcinoma (HNSCC development and progression has not yet been defined and their diagnostic or prognostic significance is controversial. Advances in the understanding of the molecular basis of head and neck cancer should help in the identification of new markers that could be used for the diagnosis, prognosis and treatment of the disease.

Mis-specified cells die by an active gene-directed process, and inhibition of this death results in cell fate transformation in Drosophila

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Werz, Christian; Lee, Tom V.; Lee, Peter L.; Lackey, Melinda; Bolduc, Clare; Stein, David S.; Bergmann, Andreas

2009-01-01

Summary Incorrectly specified or mis-specified cells often undergo cell death or are transformed to adopt a different cell fate during development. The underlying cause for this distinction is largely unknown. In many developmental mutants in Drosophila, large numbers of mis-specified cells die synchronously, providing a convenient model for analysis of this phenomenon. The maternal mutant bicoid is particularly useful model with which to address this issue because its mutant phenotype is a combination of both transformation of tissue (acron to telson) and cell death in the presumptive head and thorax regions. We show that a subset of these mis-specified cells die through an active gene-directed process involving transcriptional upregulation of the cell death inducer hid. Upregulation of hid also occurs in oskar mutants and other segmentation mutants. In hid bicoid double mutants, mis-specified cells in the presumptive head and thorax survive and continue to develop, but they are transformed to adopt a different cell fate. We provide evidence that the terminal torso signaling pathway protects the mis-specified telson tissue in bicoid mutants from hid-induced cell death, whereas mis-specified cells in the head and thorax die, presumably because equivalent survival signals are lacking. These data support a model whereby mis-specification can be tolerated if a survival pathway is provided, resulting in cellular transformation. PMID:16280349

Cancer stem cells in head and neck cancer

Directory of Open Access Journals (Sweden)

Trapasso S

2012-11-01

Full Text Available Eugenia Allegra, Serena TrapassoOtolaryngology – Head and Neck Surgery, University Magna Graecia of Catanzaro, Catanzaro, ItalyAbstract: Cancer stem cells (CSCs, also called "cells that start the tumor," represent in themselves one of the most topical and controversial issues in the field of cancer research. Tumor stem cells are able to self-propagate in vitro (self-renewal, giving rise both to other tumor stem cells and most advanced cells in the line of differentiation (asymmetric division. A final characteristic is tumorigenicity, a fundamental property, which outlines the tumor stem cell as the only cell able to initiate the formation of a tumor when implanted in immune-deficient mice. The hypothesis of a hierarchical organization of tumor cells dates back more than 40 years, but only in 1997, thanks to the work of John Dick and Dominique Bonnet, was there the formal proof of such an organization in acute myeloid leukemia. Following this, many other research groups were able to isolate CSCs, by appropriate selection markers, in various malignancies, such as breast, brain, colon, pancreas, and liver cancers and in melanoma. To date, however, it is not possible to isolate stem cells from all types of neoplasia, particularly in solid tumors. From a therapeutic point of view, the concept of tumor stem cells implies a complete revision of conventional antineoplastic treatment. Conventional cytotoxic agents are designed to target actively proliferating cells. In the majority of cases, this is not sufficient to eliminate the CSCs, which thanks to their reduced proliferative activity and/or the presence of proteins capable of extruding chemotherapeutics from the cell are not targeted. Therefore, the theory of cancer stem cells can pose new paradigms in terms of cancer treatment. Potential approaches, even in the very early experimental stages, relate to the selective inhibition of pathways connected with self-renewal, or more specifically based on

Tumor and Stromal-Based Contributions to Head and Neck Squamous Cell Carcinoma Invasion

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Markwell, Steven M.; Weed, Scott A., E-mail: scweed@hsc.wvu.edu [Department of Neurobiology and Anatomy, Program in Cancer Cell Biology, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506 (United States)

2015-02-27

Head and neck squamous cell carcinoma (HNSCC) is typically diagnosed at advanced stages with evident loco-regional and/or distal metastases. The prevalence of metastatic lesions directly correlates with poor patient outcome, resulting in high patient mortality rates following metastatic development. The progression to metastatic disease requires changes not only in the carcinoma cells, but also in the surrounding stromal cells and tumor microenvironment. Within the microenvironment, acellular contributions from the surrounding extracellular matrix, along with contributions from various infiltrating immune cells, tumor associated fibroblasts, and endothelial cells facilitate the spread of tumor cells from the primary site to the rest of the body. Thus far, most attempts to limit metastatic spread through therapeutic intervention have failed to show patient benefit in clinic trails. The goal of this review is highlight the complexity of invasion-promoting interactions in the HNSCC tumor microenvironment, focusing on contributions from tumor and stromal cells in order to assist future therapeutic development and patient treatment.

Rotation and direction judgment from visual images head-slaved in two and three degrees-of-freedom.

Science.gov (United States)

Adelstein, B D; Ellis, S R

2000-03-01

The contribution to spatial awareness of adding a roll degree-of-freedom (DOF) to telepresence camera platform yaw and pitch was examined in an experiment where subjects judged direction and rotation of stationary target markers in a remote scene. Subjects viewed the scene via head-slaved camera images in a head-mounted display. Elimination of the roll DOF affected rotation judgment, but only at extreme yaw and pitch combinations, and did not affect azimuth and elevation judgement. Systematic azimuth overshoot occurred regardless of roll condition. Observed rotation misjudgments are explained by kinematic models for eye-head direction of gaze.

Llama-derived single variable domains (nanobodies) directed against chemokine receptor CXCR7 reduce head and neck cancer cell growth in vivo.

Science.gov (United States)

Maussang, David; Mujić-Delić, Azra; Descamps, Francis J; Stortelers, Catelijne; Vanlandschoot, Peter; Stigter-van Walsum, Marijke; Vischer, Henry F; van Roy, Maarten; Vosjan, Maria; Gonzalez-Pajuelo, Maria; van Dongen, Guus A M S; Merchiers, Pascal; van Rompaey, Philippe; Smit, Martine J

2013-10-11

The chemokine receptor CXCR7, belonging to the membrane-bound G protein-coupled receptor superfamily, is expressed in several tumor types. Inhibition of CXCR7 with either small molecules or small interference (si)RNA has shown promising therapeutic benefits in several tumor models. With the increased interest and effectiveness of biologicals inhibiting membrane-bound receptors we made use of the "Nanobody platform" to target CXCR7. Previously we showed that Nanobodies, i.e. immunoglobulin single variable domains derived from naturally occurring heavy chain-only camelids antibodies, represent new biological tools to efficiently tackle difficult drug targets such as G protein-coupled receptors. In this study we developed and characterized highly selective and potent Nanobodies against CXCR7. Interestingly, the CXCR7-targeting Nanobodies displayed antagonistic properties in contrast with previously reported CXCR7-targeting agents. Several high affinity CXCR7-specific Nanobodies potently inhibited CXCL12-induced β-arrestin2 recruitment in vitro. A wide variety of tumor biopsies was profiled, showing for the first time high expression of CXCR7 in head and neck cancer. Using a patient-derived CXCR7-expressing head and neck cancer xenograft model in nude mice, tumor growth was inhibited by CXCR7-targeting Nanobody therapy. Mechanistically, CXCR7-targeting Nanobodies did not inhibit cell cycle progression but instead reduced secretion of the angiogenic chemokine CXCL1 from head and neck cancer cells in vitro, thus acting here as inverse agonists, and subsequent angiogenesis in vivo. Hence, with this novel class of CXCR7 inhibitors, we further substantiate the therapeutic relevance of targeting CXCR7 in head and neck cancer.

Cetuximab And The Head And Neck Squamous Cell Cancer.

Science.gov (United States)

Concu, Riccardo; Cordeiro, Maria Natalia Dias Soeiro

2018-01-12

The head and neck squamous cell cancer (HNSCC) is the most common type of head and neck cancer (more than 90%), and all over the world more than a half million people have been developing this cancer in the last years. This type of cancer is usually marked by a poor prognosis with a really significant morbidity and mortality. Cetuximab received early favor as an exciting and promising new therapy with relatively mild side effect, and due to this received authorization in the 2004 from the European Medicines Agency (EMA) and in the 2006 from the Food and Drug Association (FDA) for the treatment of patients with squamous cell cancer of the head and neck in combination with radiation therapy for locally advanced disease. In this work we will review the application and the efficacy of the Cetuximab in the treatment of the HNSCC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Intratumoral injection of radioactive holmium-166 microspheres in recurrent head and neck squamous cell carcinoma : preliminary results of first use

NARCIS (Netherlands)

Bakker, Robbert C; van Es, Robert J J; Rosenberg, Antoine J W P; van Nimwegen, Sebastiaan A; Bastiaannet, Remco; de Jong, Hugo W A M; Nijsen, Johannes F W; Lam, Marnix G E H

BACKGROUND: Limited treatment options exist for patients with locoregional recurrences of head and neck squamous cell carcinoma (HNSCC). In the palliative setting, a single session, minimally invasive, and relatively safe therapy is desirable. This case series illustrates the feasibility of a direct

Effects of in vitro lactoferricin and lactoferrin on the head kidney cells of European sea bass (Dicentrarchus labrax, L.).

Science.gov (United States)

Henry, Morgane A; Alexis, Maria N

2009-08-15

Antimicrobial, anti-inflammatory and immunomodulating properties of lactoferrin have been demonstrated in mammals and in fish. However, in vivo, lactoferrin is digested by gastric pepsin treatment into the N-terminal derived peptide named lactoferricin. This has been so far overlooked in fish in vitro studies. The aim of the present study was to assess in vitro the effects of both lactoferricin and lactoferrin on the head kidney cells of European sea bass (Dicentrarchus labrax, L.) in order to determine their potential as dietary additives and to get some insight into their mode of action. In vitro lactoferricin decreased significantly the chemiluminescent response of head kidney cells but did not affect the zymosan-triggered chemiluminescence activity. On the other hand, a high concentration of lactoferrin directly stimulated chemiluminescence but reduced the zymosan-triggered chemiluminescence. The bactericidal activity of head kidney cells was also significantly diminished by pre-incubation with lactoferrin in a dose-dependent manner. Although no significant effect of lactoferricin or lactoferrin was evidenced on head kidney cellular viability, absent or negative effect on the priming of respiratory burst activity suggested that care should be taken when using lactoferrin in the diet of sea bass and high doses should be avoided. Hypotheses about the mechanisms of action of lactoferricin and lactoferrin are presented.

Human Papilloma Virus (HPV) Induced Head & Neck Squamous Cell Carcinoma: A Comprehensive Retrospect

Science.gov (United States)

Nishat, Roquaiya; Ramachandra, Sujatha; Kumar, Harish; Bandyopadhyay, Alokenath

2015-01-01

Head and Neck Squamous Cell Carcinoma accounts for the sixth most common malignancy occurring worldwide with tobacco and alcohol being the two well established risk factors. In the recent years, substantial evidence has been obtained that Human Papilloma Virus (HPV) associated head and neck cancers are on the rise. This article provides an insight into the structure of HPV genome, molecular pathogenesis, detection methods and clinical implications of HPV positive Head and Neck Squamous Cell Carcinoma. PMID:26266234

Radiosensitization of head and neck cancer cells by the phytochemical agent sulforaphane

International Nuclear Information System (INIS)

Kotowski, Ulana; Heiduschka, Gregor; Brunner, Markus; Fahim, Tammer; Thurnher, Dietmar; Czembirek, Cornelia; Eder-Czembirek, Christina; Schmidt, Rainer

2011-01-01

Sulforaphane is a naturally occurring compound found in broccoli and other cruciferous vegetables. Recently it gained attention because of its antiproliferative properties in many cancer cell lines. The aim of this study was to investigate whether sulforaphane could act as a radiosensitizer in head and neck squamous cell carcinoma cell lines. Four head and neck squamous cell carcinoma cell lines (i.e., (HNSCC) SCC9, SCC25, CAL27, and FADU) were treated with sulforaphane and subsequently irradiated. Then proliferation and clonogenic assays were performed. Apoptosis was detected by flow cytometry. Possible regulation of Akt and Mcl-1 was investigated by western blotting. Sulforaphane and radiation in combination leads to stronger inhibition of cell proliferation and of clonogenic survival than each treatment method alone. Western blot analysis of Akt and Mcl-1 showed no changed expression. Sulforaphane is a promising agent in the treatment of head and neck cancer due to its antiproliferative and radio-sensitizing properties. A combination of sulforaphane and radiation decreases clonogenic survival. Apoptosis is not regulated through Akt or the Mcl-1 protein. (orig.)

Radiosensitization of head and neck cancer cells by the phytochemical agent sulforaphane

Energy Technology Data Exchange (ETDEWEB)

Kotowski, Ulana; Heiduschka, Gregor; Brunner, Markus; Fahim, Tammer; Thurnher, Dietmar [Medical University of Vienna (Austria). Dept. of Otorhinolaryngology, Head and Neck Surgery; Czembirek, Cornelia; Eder-Czembirek, Christina [Medical University of Vienna (Austria). Dept. of Cranio-, Maxillofacial and Oral Surgery; Schmidt, Rainer [Medical University of Vienna (Austria). Dept. of Radiotherapy and -biology

2011-09-15

Sulforaphane is a naturally occurring compound found in broccoli and other cruciferous vegetables. Recently it gained attention because of its antiproliferative properties in many cancer cell lines. The aim of this study was to investigate whether sulforaphane could act as a radiosensitizer in head and neck squamous cell carcinoma cell lines. Four head and neck squamous cell carcinoma cell lines (i.e., (HNSCC) SCC9, SCC25, CAL27, and FADU) were treated with sulforaphane and subsequently irradiated. Then proliferation and clonogenic assays were performed. Apoptosis was detected by flow cytometry. Possible regulation of Akt and Mcl-1 was investigated by western blotting. Sulforaphane and radiation in combination leads to stronger inhibition of cell proliferation and of clonogenic survival than each treatment method alone. Western blot analysis of Akt and Mcl-1 showed no changed expression. Sulforaphane is a promising agent in the treatment of head and neck cancer due to its antiproliferative and radio-sensitizing properties. A combination of sulforaphane and radiation decreases clonogenic survival. Apoptosis is not regulated through Akt or the Mcl-1 protein. (orig.)

Low hydrostatic head electrolyte addition to fuel cell stacks

International Nuclear Information System (INIS)

Kothmann, R.E.

1983-01-01

A fuel cell and system for supply electrolyte, as well as fuel and an oxidant to a fuel cell stack having at least two fuel cells, each of the cells having a pair of spaced electrodes and a matrix sandwiched therebetween, fuel and oxidant paths associated with a bipolar plate separating each pair of adjacent fuel cells and an electrolyte fill path for adding electrolyte to the cells and wetting said matrices. Electrolyte is flowed through the fuel cell stack in a back and forth fashion in a path in each cell substantially parallel to one face of opposite faces of the bipolar plate exposed to one of the electrodes and the matrices to produce an overall head uniformly between cells due to frictional pressure drop in the path for each cell free of a large hydrostatic head to thereby avoid flooding of the electrodes. The bipolar plate is provided with channels forming paths for the flow of the fuel and oxidant on opposite faces thereof, and the fuel and the oxidant are flowed along a first side of the bipolar plate and a second side of the bipolar plate through channels formed into the opposite faces of the bipolar plate, the fuel flowing through channels formed into one of the opposite faces and the oxidant flowing through channels formed into the other of the opposite faces

Synthetic Aperture Computation as the Head is Turned in Binaural Direction Finding

Directory of Open Access Journals (Sweden)

Duncan Tamsett

2017-03-01

Full Text Available Binaural systems measure instantaneous time/level differences between acoustic signals received at the ears to determine angles λ between the auditory axis and directions to acoustic sources. An angle λ locates a source on a small circle of colatitude (a lamda circle on a sphere symmetric about the auditory axis. As the head is turned while listening to a sound, acoustic energy over successive instantaneous lamda circles is integrated in a virtual/subconscious field of audition. The directions in azimuth and elevation to maxima in integrated acoustic energy, or to points of intersection of lamda circles, are the directions to acoustic sources. This process in a robotic system, or in nature in a neural implementation equivalent to it, delivers its solutions to the aurally informed worldview. The process is analogous to migration applied to seismic profiler data, and to that in synthetic aperture radar/sonar systems. A slanting auditory axis, e.g., possessed by species of owl, leads to the auditory axis sweeping the surface of a cone as the head is turned about a single axis. Thus, the plane in which the auditory axis turns continuously changes, enabling robustly unambiguous directions to acoustic sources to be determined.

Merkel cell carcinoma of the head and neck

NARCIS (Netherlands)

Takes, R. P.; Balm, A. J.; Loftus, B. M.; Baris, G.; Hilgers, F. J.; Gregor, R. T.

1994-01-01

Merkel cell carcinoma is a rare cutaneous tumour that typically arises in the head and neck area of elderly patients. The tumour often follows an aggressive course with frequent local recurrences and (regional) metastases, especially when localized above the clavicles. Five patients with a Merkel

Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines

International Nuclear Information System (INIS)

Kotowski, Ulana; Heiduschka, Gregor; Eckl-Dorna, Julia; Kranebitter, Veronika; Stanisz, Isabella; Brunner, Markus; Lill, Claudia; Thurnher, Dietmar; Seemann, Rudolf; Schmid, Rainer

2015-01-01

Cafestol is a diterpene molecule found in coffee beans and has anticarcinogenic properties. The aim of the study was to examine the effects of cafestol in head and neck squamous cell carcinoma (HNSCC) cells. Three HNSCC cell lines (SCC25, CAL27 and FaDu) were treated with increasing doses of cafestol. Then combination experiments with cisplatin and irradiation were carried out. Drug interactions and possible synergy were calculated using the combination index analysis. Clonogenic assays were performed after irradiation with 2, 4, 6 and 8 Gy, respectively, and the rate of apoptosis was measured with flow cytometry. Treatment of HNSCC cells with cafestol leads to a dose-dependent reduction of cell viability and to induction of apoptosis. Combination with irradiation shows a reduction of clonogenic survival compared to each treatment method alone. In two of the cell lines a significant additive effect was observed. Cafestol is a naturally occurring effective compound with growth-inhibiting properties in head and neck cancer cells. Moreover, it leads to a significant inhibition of colony formation. (orig.) [de

Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Winter, Stuart C; Stephenson, Sally-Anne; Subramaniam, Selva K; Paleri, Vinidh; Ha, Kien; Marnane, Conor; Krishnan, Suren; Rees, Guy

2009-01-01

Techniques for detecting circulating tumor cells in the peripheral blood of patients with head and neck cancers may identify individuals likely to benefit from early systemic treatment. Reconstruction experiments were used to optimise immunomagnetic enrichment and RT-PCR detection of circulating tumor cells using four markers (ELF3, CK19, EGFR and EphB4). This method was then tested in a pilot study using samples from 16 patients with advanced head and neck carcinomas. Seven patients were positive for circulating tumour cells both prior to and after surgery, 4 patients were positive prior to but not after surgery, 3 patients were positive after but not prior to surgery and 2 patients were negative. Two patients tested positive for circulating cells but there was no other evidence of tumor spread. Given this patient cohort had mostly advanced disease, as expected the detection of circulating tumour cells was not associated with significant differences in overall or disease free survival. For the first time, we show that almost all patients with advanced head and neck cancers have circulating cells at the time of surgery. The clinical application of techniques for detection of spreading disease, such as the immunomagnetic enrichment RT-PCR analysis used in this study, should be explored further

The effect of radiotherapy on NKT cells in patients with advanced head and neck cancer.

Science.gov (United States)

Kobayashi, Kouichi; Tanaka, Yuriko; Horiguchi, Shigetoshi; Yamamoto, Shouji; Toshinori, Nakayama; Sugimoto, Akira; Okamoto, Yoshitaka

2010-10-01

Cancer immunotherapy with NKT cells is a potential new treatment strategy for advanced head and neck cancer. NKT cell therapy is promising due to its unique anti-tumor activity and higher degree of safety compared to current therapies. Radiotherapy is indispensable as a standard treatment for advanced head and neck cancer. To elucidate the possibility of using NKT cells as an adjuvant immunotherapy with radiotherapy, we examined the effect of radiotherapy on NKT cells in patients with head and neck cancer. The number, IFN-gamma production and proliferation capacity of NKT cells were analyzed before and after 50 Gy radiation therapy in 12 patients with stage IV head and neck squamous cell carcinoma. The cytotoxic activity of NKT cells was examined in vitro. The number of NKT cells in the blood varied widely between patients. After radiation therapy, the population of CD3 T cells decreased significantly, while the NKT cell population remained stable. The number of NKT cells was the same after radiation therapy as before. IFN-gamma production from NKT cells collected just after radiotherapy was impaired after stimulation with exogenous ligand, but the proliferative responses of these NKT cells was enhanced in comparison to those collected before radiation therapy. Furthermore, the proliferated NKT cells displayed a significant level of anti-tumor activity. NKT cells are relatively resistant to radiation and might therefore be suitable for adjuvant immunotherapy to eradicate remnant cancer cells in patients who have undergone radiation therapy.

Kinematics of the AM-50 heading machine cutting head

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Sikora, W; Bak, K; Klich, R [Politechnika Slaska, Gliwice (Poland). Instytut Mechanizacji Gornictwa

1987-01-01

Analyzes motion of the cutter head of the AM-50 heading machine. Two types of head motion are comparatively evaluated: planar motion and spatial motion. The spatial motion consists of the head rotational motion and horizontal or vertical feed motion, while planar motion consists of rotational motion and vertical feed motion. Equations that describe head motion under conditions of cutter vertical or horizontal feed motion are derived. The angle between the cutting speed direction and working speed direction is defined. On the basis of these formulae variations of cutting speed depending on the cutting tool position on a cutter head are calculated. Calculations made for 2 extreme cutting tools show that the cutting speed ranges from 1,205 m/s to 3,512 m/s. 4 refs.

Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck

NARCIS (Netherlands)

Michalides, R.; van Veelen, N.; Hart, A.; Loftus, B.; Wientjens, E.; Balm, A.

1995-01-01

We evaluated the prognostic significance of overexpression of cyclin D1 in 47 patients with surgically resected squamous cell carcinomas of the head and neck. Overexpression of cyclin D1 was detected immunohistochemically using an affinity-purified polyclonal antibody directed against the

Hydrolyzed fish proteins modulates both inflammatory and antioxidant gene expression as well as protein expression in a co culture model of liver and head kidney cells isolated from Atlantic salmon (Salmo salar).

Science.gov (United States)

Holen, Elisabeth; He, Juyun; Araujo, Pedro; Seliussen, Jørgen; Espe, Marit

2016-07-01

Hydrolyzed fish proteins (H-pro) contain high concentrations of free amino acids and low molecular peptides that potentially may benefit fish health. The following study aimed to test whether the water-soluble phase of H-pro could attenuate lipopolysaccharide (LPS) provoked inflammation in liver cells and head kidney cells isolated from Atlantic salmon. Cells were grown as mono cultures or co cultures to assess possible crosstalk between immune cells and metabolic cells during treatments. Cells were added media with or without H-pro for 2 days before LPS exposure and harvested 24 h post LPS exposure. Respective cells without H-pro and LPS were used as controls. H-pro alone could affect expression of proteins directly as H-pro increased catalase protein expression in head kidney- and liver cells, regardless of culturing methods and LPS treatment. Leukotriene B4 (LTB4) production was also increased by H-pro in head kidney cells co cultured with liver cells. H-pro increased LPS induced interleukin 1β (IL-1β) transcription in liver cells co cultured with head kidney cells. All cultures of head kidney cells showed a significant increase in IL-1β transcription when treated with H-pro + LPS. H-pro decreased caspase-3 transcription in liver cells cultured co cultured with head kidney cells. Peroxisome proliferator activated receptor α (PPAR α) was upregulated, regardless of treatment, in liver cells co cultured with head kidney cells clearly showing that culturing method alone affected gene transcription. H-pro alone and together with LPS as an inflammation inducer, affect both antioxidant and inflammatory responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of radiotherapy on stem cells in head and neck region

International Nuclear Information System (INIS)

Sharma, Anu; Krishnan, Manu

2014-01-01

Head and neck cancers form a major group of dreaded diseases in India. Radiation therapy is one important treatment modality for this type of cancer. However, inadvertent radiation to normal tissue leads to depletion of its critical stem cells due to genotoxic damage. Cells mostly affected by radiation are rapidly dividing bone marrow and epidermal skin stem cells. The erythroid and myeloid progenitor cells of bone marrow bear the brunt of it causing leucopenia/thrombocytopenia/anemia. Alopecia and pigmentation mark the changes on skin. In brain, two stem cell populations; subgranular and subventricular zones, where neurogenesis occurs throughout life are affected. However, terminally differentiating neurons with low proliferative capacity are spared. In oral tissues, xerostomia is a prominent feature, while dental pulp stem cells undergo senescence. Enamel calcification and tooth root formation are also impaired. Eye shows changes in the limbal stem cells that replace corneal epithelium. All these imply a varied response of stem cells to radiation therapy based on their proliferation capacity; quiescent stem cells being more resistant whereas actively dividing cells, less resistant to radiotherapy. This paper evaluates the differential response of stem cells to radiation therapy in the head and neck area and thereby aims to predict their therapeutic potential. (author)

Slow-cycling stem cells in hydra contribute to head regeneration

Directory of Open Access Journals (Sweden)

Niraimathi Govindasamy

2014-11-01

Full Text Available Adult stem cells face the challenge of maintaining tissue homeostasis by self-renewal while maintaining their proliferation potential over the lifetime of an organism. Continuous proliferation can cause genotoxic/metabolic stress that can compromise the genomic integrity of stem cells. To prevent stem cell exhaustion, highly proliferative adult tissues maintain a pool of quiescent stem cells that divide only in response to injury and thus remain protected from genotoxic stress. Hydra is a remarkable organism with highly proliferative stem cells and ability to regenerate at whole animal level. Intriguingly, hydra does not display consequences of high proliferation, such as senescence or tumour formation. In this study, we investigate if hydra harbours a pool of slow-cycling stem cells that could help prevent undesirable consequences of continuous proliferation. Hydra were pulsed with the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU and then chased in the absence of EdU to monitor the presence of EdU-retaining cells. A significant number of undifferentiated cells of all three lineages in hydra retained EdU for about 8–10 cell cycles, indicating that these cells did not enter cell cycle. These label-retaining cells were resistant to hydroxyurea treatment and were predominantly in the G2 phase of cell cycle. Most significantly, similar to mammalian quiescent stem cells, these cells rapidly entered cell division during head regeneration. This study shows for the first time that, contrary to current beliefs, cells in hydra display heterogeneity in their cell cycle potential and the slow-cycling cells in this population enter cell cycle during head regeneration. These results suggest an early evolution of slow-cycling stem cells in multicellular animals.

Indications for direct multidirectional or multiplanar electronic reconstructions in CT-scanning of the head

International Nuclear Information System (INIS)

Kaiser, M.C.; Veiga-Pires, J.A.; Gooskens, R.; Troost, J.

1982-01-01

The authors set out to indicate the optimal applications at minimum radiation penalty of both direct multidirectional and multiplanar electronic reconstruction modes in CT-scanning of the head by means of two illustrative case reports of midline congenital tumours. (orig.)

Mechanisms of taste bud cell loss after head and neck irradiation.

Science.gov (United States)

Nguyen, Ha M; Reyland, Mary E; Barlow, Linda A

2012-03-07

Taste loss in human patients following radiotherapy for head and neck cancer is a common and significant problem, but the cellular mechanisms underlying this loss are not understood. Taste stimuli are transduced by receptor cells within taste buds, and like epidermal cells, taste cells are regularly replaced throughout adult life. This renewal relies on progenitor cells adjacent to taste buds, which continually supply new cells to each bud. Here we treated adult mice with a single 8 Gy dose of x-ray irradiation to the head and neck, and analyzed taste epithelium at 1-21 d postirradiation (dpi). We found irradiation targets the taste progenitor cells, which undergo cell cycle arrest (1-3 dpi) and apoptosis (within 1 dpi). Taste progenitors resume proliferation at 5-7 dpi, with the proportion of cells in S and M phase exceeding control levels at 5-6 and 6 dpi, respectively, suggesting that proliferation is accelerated and/or synchronized following radiation damage. Using 5-bromo-2-deoxyuridine birthdating to identify newborn cells, we found that the decreased proliferation following irradiation reduces the influx of cells at 1-2 dpi, while the robust proliferation detected at 6 dpi accelerates entry of new cells into taste buds. In contrast, the number of differentiated taste cells was not significantly reduced until 7 dpi. These data suggest a model where continued natural taste cell death, paired with temporary interruption of cell replacement, underlies taste loss after irradiation.

Mechanisms of taste bud cell loss after head and neck irradiation

Science.gov (United States)

Nguyen, Ha M.; Reyland, Mary E.; Barlow, Linda A.

2012-01-01

Taste loss in human patients following radiotherapy for head and neck cancer is a common and significant problem, but the cellular mechanisms underlying this loss are not understood. Taste stimuli are transduced by receptor cells within taste buds, and like epidermal cells, taste cells are regularly replaced throughout adult life. This renewal relies on a progenitor cells adjacent to taste buds, which continually supply new cells to each bud. Here we treated adult mice with a single 8 Gy dose of X-ray irradiation to the head and neck, and analyzed taste epithelium at 1–21 days post-irradiation (dpi). We found irradiation targets the taste progenitor cells, which undergo cell cycle arrest (1–3 dpi) and apoptosis (within 1 dpi). Taste progenitors resume proliferation at 5–7 dpi, with the proportion of cells in S and M phase exceeding control levels at 5–6 and 6 dpi, respectively, suggesting that proliferation is accelerated and/or synchronized following radiation damage. Using BrdU birthdating to identify newborn cells, we found that the decreased proliferation following irradiation reduces the influx of cells at 1–2 dpi, while the robust proliferation detected at 6 dpi accelerates entry of new cells into taste buds. By contrast, the number of differentiated taste cells was not significantly reduced until 7 dpi. These data suggest a model where continued natural taste cell death, paired with temporary interruption of cell replacement underlies taste loss after irradiation. PMID:22399770

Devascularization of Head and Neck Paragangliomas by Direct Percutaneous Embolization

International Nuclear Information System (INIS)

Ozyer, Umut; Harman, Ali; Yildirim, Erkan; Aytekin, Cuneyt; Akay, Tankut Hakki; Boyvat, Fatih

2010-01-01

Preoperative transarterial embolization of head and neck paragangliomas using particulate agents has proven beneficial for decreasing intraoperative blood loss. However, the procedure is often incomplete owing to extensive vascular structure and arteriovenous shunts. We report our experience with embolization of these lesions by means of direct puncture and intratumoral injection of n-butyl cyanoacrylate (NBCA) or Onyx. Ten patients aged 32-82 years who were referred for preoperative embolization of seven carotid body tumors and three jugular paragangliomas were retrospectively analyzed. Intratumoral injections were primarily performed in four cases with multiple small-caliber arterial feeders and adjunctive to transarterial embolization in six cases with incomplete devascularization. Punctures were performed under ultrasound and injections were performed under roadmap fluoroscopic guidance. Detailed angiographies were performed before and after embolization procedures. Control angiograms showed complete or near-complete devascularization in all tumors. Three tumors with multiple small-caliber arterial feeders were treated with primary NBCA injections. One tumor necessitated transarterial embolization after primary injection of Onyx. Six tumors showed regional vascularization from the vasa vasorum or small-caliber branches of the external carotid artery following the transarterial approach. These regions were embolized with NBCA injections. No technical or clinical complications related to embolization procedures occurred. All except one of the tumors were surgically removed following embolization. In conclusion, preoperative devascularization with percutaneous direct injection of NBCA or Onyx is feasible, safe, and effective in head and neck paragangliomas with multiple small-caliber arterial feeders and in cases of incomplete devascularization following transarterial embolization.

Parallel and convergent processing in grid cell, head-direction cell, boundary cell, and place cell networks.

Science.gov (United States)

Brandon, Mark P; Koenig, Julie; Leutgeb, Stefan

2014-03-01

The brain is able to construct internal representations that correspond to external spatial coordinates. Such brain maps of the external spatial topography may support a number of cognitive functions, including navigation and memory. The neuronal building block of brain maps are place cells, which are found throughout the hippocampus of rodents and, in a lower proportion, primates. Place cells typically fire in one or few restricted areas of space, and each area where a cell fires can range, along the dorsoventral axis of the hippocampus, from 30 cm to at least several meters. The sensory processing streams that give rise to hippocampal place cells are not fully understood, but substantial progress has been made in characterizing the entorhinal cortex, which is the gateway between neocortical areas and the hippocampus. Entorhinal neurons have diverse spatial firing characteristics, and the different entorhinal cell types converge in the hippocampus to give rise to a single, spatially modulated cell type-the place cell. We therefore suggest that parallel information processing in different classes of cells-as is typically observed at lower levels of sensory processing-continues up into higher level association cortices, including those that provide the inputs to hippocampus. WIREs Cogn Sci 2014, 5:207-219. doi: 10.1002/wcs.1272 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. © 2013 John Wiley & Sons, Ltd.

The Relationship Between Human Papillomavirus Status and Other Molecular Prognostic Markers in Head and Neck Squamous Cell Carcinomas

International Nuclear Information System (INIS)

Kong, Christina S.; Narasimhan, Balasubramanian; Cao Hongbin; Kwok, Shirley; Erickson, Julianna P.; Koong, Albert; Pourmand, Nader; Le, Quynh-Thu

2009-01-01

Purpose: To evaluate the relationship between human papillomavirus (HPV) status and known prognostic makers for head and neck cancers including tumor hypoxia, epidermal growth factor receptor (EGFR) expression and intratumoral T-cell levels and to determine the prognostic impact of these markers by HPV status. Methods and Materials: HPV status in 82 evaluable head and neck squamous cell carcinomas patients was determined by pyrosequencing and related to p16 INK4a staining and treatment outcomes. It was correlated with tumor hypoxia (tumor pO 2 and carbonic anhydrase [CAIX] staining), EGFR status, and intratumoral lymphocyte expression (CD3 staining). Results: Forty-four percent of evaluable tumors had strong HPV signal by pyrosequencing. There was a significant relationship between strong HPV signal and p16 INK4a staining as well as oropharynx location. The strong HPV signal group fared significantly better than others, both in time to progression (TTP, p = 0.008) and overall survival (OS, p = 0.004) for all patients and for the oropharyngeal subset. Positive p16 INK4a staining was associated with better TTP (p = 0.014) and OS (p = 0.00002). There was no relationship between HPV status and tumor pO 2 or CAIX staining. However, HPV status correlated inversely with EGFR reactivity (p = 0.0006) and directly with CD3(+) T-lymphocyte level (p = 0.03). Whereas CAIX and EGFR overexpression were negative prognostic factors regardless of HPV status, CD3(+) T-cell levels was prognostic only in HPV(-) tumors. Conclusion: HPV status was a prognostic factor for progression and survival. It correlated inversely with EGFR expression and directly with T-cell infiltration. The prognostic effect of CAIX and EGFR expression was not influenced by HPV status, whereas intratumoral T-cell levels was significant only for HPV(-) tumors.

Individualized directional microphone optimization in hearing aids based on reconstructing the 3D geometry of the head and ear from 2D images

DEFF Research Database (Denmark)

Harder, Stine

head model based on 2D images, the second step is to simulate individual head related transfer functions (HRTFs) based on the estimated 3D head model and the final step is to calculate optimal directional filters based on the simulated HRTFs. The pipeline is employed on a Behind-The-Ear (BTE) hearing...... against non-individual directional filters revealed equally high Articulation-Index weighted Directivity Index (AI-DI) values for our specific test subject. However, measurements on other individuals indicate that the performance of the non-individual filters vary among subjects, and in particular...

MicroRNA expression profiles of cancer stem cells in head and neck squamous cell carcinoma

OpenAIRE

YATA, KAZUYA; BEDER, LEVENT BEKIR; TAMAGAWA, SHUNJI; HOTOMI, MUNEKI; HIROHASHI, YOSHIHIKO; GRENMAN, REIDAR; YAMANAKA, NOBORU

2015-01-01

Increasing evidence indicates that cancer stem cells have essential roles in tumor initiation, progression, metastasis and resistance to chemo-radiation. Recent research has pointed out biological importance of microRNAs in cancer stem cell dysregulation. Total number of mature microRNAs in human genome increased to more than 2,500 with the recent up-date of the database. However, currently no information is available regarding microRNA expression profiles of cancer stem cells in head and nec...

Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma.

Science.gov (United States)

Misawa, Yuki; Misawa, Kiyoshi; Kawasaki, Hideya; Imai, Atsushi; Mochizuki, Daiki; Ishikawa, Ryuji; Endo, Shiori; Mima, Masato; Kanazawa, Takeharu; Iwashita, Toshihide; Mineta, Hiroyuki

2017-07-01

The aim of this study was to determine the methylation status of the genes encoding the vascular endothelial growth factor receptors and to evaluate the usefulness of VEGFR methylation as a prognostic indicator in head and neck squamous cell carcinoma. VEGFR messenger RNA expression and promoter methylation were examined in a panel of cell lines via quantitative reverse transcription and methylation-specific polymerase chain reaction, respectively. Promoter methylation was compared with clinical characteristics in 128 head and neck squamous cell carcinoma samples. The normalized methylation values for the VEGFR1, VEGFR2 and VEGFR3 promoters tended to be higher in the tumour cell lines than in normal tonsil samples, whereas amounts of VEGFR1, VEGFR2 and VEGFR3 messenger RNA were significantly higher. Methylation of the VEGFR1 promoter (p = 0.003; 66/128 head and neck squamous cell carcinoma samples, 52%) and VEGFR3 promoter (p = 0.043; 53/128 head and neck squamous cell carcinoma samples, 41%) significantly correlated with recurrence, whereas methylation of the VEGFR2 promoter significantly correlated with lymph node metastasis (p = 0.046; 47/128 head and neck squamous cell carcinoma samples, 37%). Concurrent methylation of the VEGFR1 and VEGFR3 promoters significantly correlated with reduced disease-free survival (log-rank test, p = 0.009). In a multivariate logistic regression analysis, methylation of the VEGFR1, VEGFR3 and both the VEGFR1 and VEGFR3 promoters independently predicted recurrence (odds ratios and 95% confidence intervals: 3.19, 1.51-6.75 (p = 0.002); 2.24, 1.06-4.76 (p = 0.035); and 2.56, 1.09-6.05 (p = 0.032), respectively). Methylation of the VEGFR promoters predicts poor prognosis in head and neck squamous cell carcinoma patients.

The neuroendocrine (Merkel cell) carcinoma of head and neck

International Nuclear Information System (INIS)

Weidauer, H.; Altmannsberger, H.M.

1987-01-01

The neuroendocrine carcinoma of the skin has its histogenetic origin in Merkel cells and a preference in head and neck area in the seventh decade of life. The definitive diagnosis can be made with a combination of electron microscopy and immunohistochemistry. Merkel cell carcinoma is a primary cutaneous neoplasma and is rarely found on the lips or gingiva. Operation and radiation are the therapy of choice. The value of an additional antineoplastic chemotherapy in the treatment of Merkel cell carcinoma is still controversial. Although long survival times had been described in literature the occurrence of local relapses and metastases demands for frequent controls. (orig.) [de

Enhanced CAR T cell therapy: A novel approach for head and neck cancers.

Science.gov (United States)

Wang, Songlin; Zhu, Zhao

2018-05-05

Head and neck cancer that presents in locally advanced stages often results in a bad prognosis with an increased recurrence rate even after curative resections. Radiation therapy is then applied, with multiple side effects, as adjuvant regional therapy. Because of the high rate of recurrence and mortality, new therapies are needed for patients suffering from head and neck malignant tumors.CAR (chimeric antigen receptor) T cell therapy, which was first devised about 25 years ago, causes the killing or apoptosis of target tumor cells through inducing the secretion of cytokines and granzymes by T cells (Cheadle et al., 2014). CARs are comprised of three canonical domains for antigen recognition, T cell activation, and co-stimulation, and are synthetic receptors that reprogram immune cells for therapeutic treatment of multiple tumors (Sadelain, 2017). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Identification, expansion and characterization of cancer cells with stem cell properties from head and neck squamous cell carcinomas

Energy Technology Data Exchange (ETDEWEB)

Kaseb, Hatem O. [Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261 (United States); Department of Clinical Pathology, National Cancer Institute (NCI), Cairo University, Cairo (Egypt); Fohrer-Ting, Helene [Department of Pathology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219 (United States); Lewis, Dale W. [Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261 (United States); Lagasse, Eric [Department of Pathology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219 (United States); Gollin, Susanne M., E-mail: gollin@pitt.edu [Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261 (United States); University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232 (United States)

2016-10-15

Head and neck squamous cell carcinoma (HNSCC) is a major public health concern. Recent data indicate the presence of cancer stem cells (CSC) in many solid tumors, including HNSCC. Here, we assessed the stem cell (SC) characteristics, including cell surface markers, radioresistance, chromosomal instability, and in vivo tumorigenic capacity of CSC isolated from HNSCC patient specimens. We show that spheroid enrichment of CSC from early and short-term HNSCC cell cultures was associated with increased expression of CD44, CD133, SOX2 and BMI1 compared with normal oral epithelial cells. On immunophenotyping, five of 12 SC/CSC markers were homogenously expressed in all tumor cultures, while one of 12 was negative, four of 12 showed variable expression, and two of the 12 were expressed heterogeneously. We showed that irradiated CSCs survived and retained their self-renewal capacity across different ionizing radiation (IR) regimens. Fluorescence in situ hybridization (FISH) analyses of parental and clonally-derived tumor cells revealed different chromosome copy numbers from cell to cell, suggesting the presence of chromosomal instability in HNSCC CSC. Further, our in vitro and in vivo mouse engraftment studies suggest that CD44+/CD66− is a promising, consistent biomarker combination for HNSCC CSC. Overall, our findings add further evidence to the proposed role of HNSCC CSCs in therapeutic resistance. - Highlights: • Spheroid enrichment selects cancer stem cells (CSC) from head & neck tumors (HNSCC). • Compared to normal epithelial cells, isolated CSC express increased SC/CSC markers. • Isolated CSC display enhanced radioresistance, clonogenicity and tumorigenicity. • HNSCC CSC express chromosomal instability. • CD44+/CD66− is a promising, consistent biomarker for HNSCC CSC.

Identification, expansion and characterization of cancer cells with stem cell properties from head and neck squamous cell carcinomas

International Nuclear Information System (INIS)

Kaseb, Hatem O.; Fohrer-Ting, Helene; Lewis, Dale W.; Lagasse, Eric; Gollin, Susanne M.

2016-01-01

Head and neck squamous cell carcinoma (HNSCC) is a major public health concern. Recent data indicate the presence of cancer stem cells (CSC) in many solid tumors, including HNSCC. Here, we assessed the stem cell (SC) characteristics, including cell surface markers, radioresistance, chromosomal instability, and in vivo tumorigenic capacity of CSC isolated from HNSCC patient specimens. We show that spheroid enrichment of CSC from early and short-term HNSCC cell cultures was associated with increased expression of CD44, CD133, SOX2 and BMI1 compared with normal oral epithelial cells. On immunophenotyping, five of 12 SC/CSC markers were homogenously expressed in all tumor cultures, while one of 12 was negative, four of 12 showed variable expression, and two of the 12 were expressed heterogeneously. We showed that irradiated CSCs survived and retained their self-renewal capacity across different ionizing radiation (IR) regimens. Fluorescence in situ hybridization (FISH) analyses of parental and clonally-derived tumor cells revealed different chromosome copy numbers from cell to cell, suggesting the presence of chromosomal instability in HNSCC CSC. Further, our in vitro and in vivo mouse engraftment studies suggest that CD44+/CD66− is a promising, consistent biomarker combination for HNSCC CSC. Overall, our findings add further evidence to the proposed role of HNSCC CSCs in therapeutic resistance. - Highlights: • Spheroid enrichment selects cancer stem cells (CSC) from head & neck tumors (HNSCC). • Compared to normal epithelial cells, isolated CSC express increased SC/CSC markers. • Isolated CSC display enhanced radioresistance, clonogenicity and tumorigenicity. • HNSCC CSC express chromosomal instability. • CD44+/CD66− is a promising, consistent biomarker for HNSCC CSC.

MRI with DWI for the Detection of Posttreatment Head and Neck Squamous Cell Carcinoma: Why Morphologic MRI Criteria Matter.

Science.gov (United States)

Ailianou, A; Mundada, P; De Perrot, T; Pusztaszieri, M; Poletti, P-A; Becker, M

2018-04-01

Although diffusion-weighted imaging combined with morphologic MRI (DWIMRI) is used to detect posttreatment recurrent and second primary head and neck squamous cell carcinoma, the diagnostic criteria used so far have not been clarified. We hypothesized that precise MRI criteria based on signal intensity patterns on T2 and contrast-enhanced T1 complement DWI and therefore improve the diagnostic performance of DWIMRI. We analyzed 1.5T MRI examinations of 100 consecutive patients treated with radiation therapy with or without additional surgery for head and neck squamous cell carcinoma. MRI examinations included morphologic sequences and DWI ( b =0 and b =1000 s/mm 2 ). Histology and follow-up served as the standard of reference. Two experienced readers, blinded to clinical/histologic/follow-up data, evaluated images according to clearly defined criteria for the diagnosis of recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment, post-radiation therapy inflammatory edema, and late fibrosis. DWI analysis included qualitative (visual) and quantitative evaluation with an ADC threshold. Recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment was present in 36 patients, whereas 64 patients had post-radiation therapy lesions only. The Cohen κ for differentiating tumor from post-radiation therapy lesions with MRI and qualitative DWIMRI was 0.822 and 0.881, respectively. Mean ADCmean in recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment (1.097 ± 0.295 × 10 -3 mm 2 /s) was significantly lower ( P .05). Although ADCs were similar in tumors and late fibrosis, morphologic MRI criteria facilitated distinction between the 2 conditions. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios (95% CI) of

'Goats that stare at men'--revisited: do dwarf goats alter their behaviour in response to eye visibility and head direction of a human?

Science.gov (United States)

Nawroth, Christian; von Borell, Eberhard; Langbein, Jan

2016-05-01

Being able to recognise when one is being observed by someone else is thought to be adaptive during cooperative or competitive events. In particular for prey species, this ability should be of use in the context of predation. A previous study reported that goats (Capra aegagrus hircus) alter their behaviour according to the body and head orientation of a human experimenter. During a food anticipation task, an experimenter remained in a particular posture for 30 s before delivering a reward, and the goats' active anticipation and standing alert behaviour were analysed. To further evaluate the specific mechanisms at work, we here present two additional test conditions. In particular, we investigated the effects of the eye visibility and head orientation of a human experimenter on the behaviour of the goats (N = 7). We found that the level of the subjects' active anticipatory behaviour was highest in the conditions where the experimenter was directing his head and body towards the goat ('Control' and 'Eyes closed' conditions), but the anticipatory behaviour was significantly decreased when the body ('Head only') or the head and body of the experimenter were directed away from the subject ('Back' condition). For standing alert, we found no significant differences between the three conditions in which the experimenter was directing his head towards the subject ('Control', 'Eyes closed' and 'Head only'). This lack of differences in the expression of standing alert suggests that goats evaluate the direction of a human's head as an important cue in their anticipatory behaviour. However, goats did not respond to the visibility of the experimenter's eyes alone.

Multiple squamous cell carcinomas within the head and neck region

International Nuclear Information System (INIS)

Sato, Katsuro; Hanazawa, Hideyuki; Sato, Yuichiro; Takahashi, Sugata

2004-01-01

Clinical features of multiple squamous cell carcinoma (SCC) cases within the head and neck that were treated in our department during the recent 10 years are discussed. Multiple SCCs arose in 6.6% of the cases with primary SCC; 67% of the cases had two carcinomas, and 33% had more than three carcinomas. The most common site of the multiple SCCs was the oral cavity (54%). The most frequent interval between treatment of previous carcinoma and diagnosis of subsequent carcinoma was simultaneous, but more than 5 years' interval was observed in 36% of the patients. The most common initial treatment of the carcinoma was irradiation, but the ratio of surgery increased for subsequent carcinomas. Prognosis of the patients with more than three carcinomas was not worse than that of patients with two carcinomas. Therefore, early diagnosis of the subsequent carcinomas based on careful long-term observation in the head and neck is necessary for follow-up of the patients with SCC of the head and neck. Treatment strategies considering the treatment of subsequent carcinomas are needed for the patients with primary head and neck SCC. (author)

Review: Head and neck squamous cell carcinoma in sub-Saharan ...

African Journals Online (AJOL)

Aim Review the literature from 1990 to 2013 to determine known anatomic sites, risk factors, treatments, and outcomes of head and neck squamous cell carcinoma (HNSCC) in sub-Saharan Africa. Methods Using a systematic search strategy, literature pertaining to HNSCC in sub-Saharan Africa was reviewed and patient ...

Receptor-type Protein Tyrosine Phosphatase β Regulates Met Phosphorylation and Function in Head and Neck Squamous Cell Carcinoma

Directory of Open Access Journals (Sweden)

Yiru Xu

2012-11-01

Full Text Available Head and neck squamous cell carcinoma (HNSCC is the sixth most common cancer and has a high rate of mortality. Emerging evidence indicates that hepatocyte growth factor receptor (or Met pathway plays a pivotal role in HNSCC metastasis and resistance to chemotherapy. Met function is dependent on tyrosine phosphorylation that is under direct control by receptor-type protein tyrosine phosphatase β (RPTP-β. We report here that RPTP-β expression is significantly downregulated in HNSCC cells derived from metastatic tumors compared to subject-matched cells from primary tumors. Knockdown of endogenous RPTP-β in HNSCC cells from primary tumor potentiated Met tyrosine phosphorylation, downstream mitogen-activated protein (MAP kinase pathway activation, cell migration, and invasion. Conversely, restoration of RPTP-β expression in cells from matched metastatic tumor decreased Met tyrosine phosphorylation and downstream functions. Furthermore, we observed that six of eight HNSCC tumors had reduced levels of RPTP-β protein in comparison with normal oral tissues. Collectively, the results demonstrate the importance of RPTP-β in tumor biology of HNSCC through direct dephosphorylation of Met and regulation of downstream signal transduction pathways. Reduced RPTP-β levels, with or without Met overexpression, could promote Met activation in HNSCC tumors.

A unified model of heading and path perception in primate MSTd.

Directory of Open Access Journals (Sweden)

Oliver W Layton

2014-02-01

Full Text Available Self-motion, steering, and obstacle avoidance during navigation in the real world require humans to travel along curved paths. Many perceptual models have been proposed that focus on heading, which specifies the direction of travel along straight paths, but not on path curvature, which humans accurately perceive and is critical to everyday locomotion. In primates, including humans, dorsal medial superior temporal area (MSTd has been implicated in heading perception. However, the majority of MSTd neurons respond optimally to spiral patterns, rather than to the radial expansion patterns associated with heading. No existing theory of curved path perception explains the neural mechanisms by which humans accurately assess path and no functional role for spiral-tuned cells has yet been proposed. Here we present a computational model that demonstrates how the continuum of observed cells (radial to circular in MSTd can simultaneously code curvature and heading across the neural population. Curvature is encoded through the spirality of the most active cell, and heading is encoded through the visuotopic location of the center of the most active cell's receptive field. Model curvature and heading errors fit those made by humans. Our model challenges the view that the function of MSTd is heading estimation, based on our analysis we claim that it is primarily concerned with trajectory estimation and the simultaneous representation of both curvature and heading. In our model, temporal dynamics afford time-history in the neural representation of optic flow, which may modulate its structure. This has far-reaching implications for the interpretation of studies that assume that optic flow is, and should be, represented as an instantaneous vector field. Our results suggest that spiral motion patterns that emerge in spatio-temporal optic flow are essential for guiding self-motion along complex trajectories, and that cells in MSTd are specifically tuned to extract

A Unified Model of Heading and Path Perception in Primate MSTd

Science.gov (United States)

Layton, Oliver W.; Browning, N. Andrew

2014-01-01

Self-motion, steering, and obstacle avoidance during navigation in the real world require humans to travel along curved paths. Many perceptual models have been proposed that focus on heading, which specifies the direction of travel along straight paths, but not on path curvature, which humans accurately perceive and is critical to everyday locomotion. In primates, including humans, dorsal medial superior temporal area (MSTd) has been implicated in heading perception. However, the majority of MSTd neurons respond optimally to spiral patterns, rather than to the radial expansion patterns associated with heading. No existing theory of curved path perception explains the neural mechanisms by which humans accurately assess path and no functional role for spiral-tuned cells has yet been proposed. Here we present a computational model that demonstrates how the continuum of observed cells (radial to circular) in MSTd can simultaneously code curvature and heading across the neural population. Curvature is encoded through the spirality of the most active cell, and heading is encoded through the visuotopic location of the center of the most active cell's receptive field. Model curvature and heading errors fit those made by humans. Our model challenges the view that the function of MSTd is heading estimation, based on our analysis we claim that it is primarily concerned with trajectory estimation and the simultaneous representation of both curvature and heading. In our model, temporal dynamics afford time-history in the neural representation of optic flow, which may modulate its structure. This has far-reaching implications for the interpretation of studies that assume that optic flow is, and should be, represented as an instantaneous vector field. Our results suggest that spiral motion patterns that emerge in spatio-temporal optic flow are essential for guiding self-motion along complex trajectories, and that cells in MSTd are specifically tuned to extract complex trajectory

Highly efficient destruction of squamous carcinoma cells of the head and neck by photochemical internalization of Ranpirnase.

Science.gov (United States)

Liebers, Nora; Holland-Letz, Tim; Welschof, Mona; Høgset, Anders; Jäger, Dirk; Arndt, Michaela A E; Krauss, Jürgen

2017-11-01

Photochemical Internalization is a novel drug delivery technology for cancer treatment based on the principle of Photodynamic Treatment. Using a photosensitizer that locates in endocytic vesicles membranes of tumor cells, Photochemical internalization enables cytosolic release of endocytosed antitumor agents in a site-specific manner. The purpose of the present in-vitro study was to explore whether Photochemical Internalization is able to enhance the efficacy of Ranpirnase, a cytotoxic amphibian ribonuclease, for eradication of squamous cell carcinoma of the head and neck. Cell viability was measured in 8 primary human cell lines of squamous cell carcinoma of the head and neck after treatment with Ranpirnase and Photochemical Internalization. For Photochemical Internalization the photosensitizer disulfonated tetraphenyl porphine was incubated with tumor cells followed by exposure to blue light (435 nm). Our study demonstrates significant enhancement of antitumor activity of Ranpirnase by Photochemical Internalization. Treatment responses were heterogeneous between the primary cancer cell lines. Combining Photochemical Internalization with Ranpirnase resulted in 4.6 to 1,940-fold increased cytotoxicity when compared with the ribonuclease alone (P Internalization in squamous cell carcinoma of the head and neck.

Antiproliferative study of B. javanica extracts against head and neck cancer cells

International Nuclear Information System (INIS)

Mohd Noor Hidayat Adenan; Zainah Adam; Shafii Khamis; Fazliana Mohd Saaya

2014-01-01

Brucea javanica or locally known as Meladapahit, are being used in Malaysia as traditional medicine mainly for the treatment of diabetes mellitus and hypertension. In order to study the potential use of this plant for cancer treatment, we have prepared crude extracts of the leaves and fruits, and assessed them for antiproliferative activities against head and neck cancer cell line which is HTB-43. The dried and ground leaves and fruits of the plant were successively extracted using hexane, chloroform, methanol and water, respectively. Inhibition of growth of the cultured cancer cells line was measured using a standard Micro culture Tetrazolium Technique (MTT) assay. The crude extracts were also subjected to toxicity test using brine shrimp lethality assay. Most of the tested crude extracts exhibited significant antiproliferative activities against the HTB-43 cell with IC 50 ranging from 8.46 μg/ml to 47.25 μg/ml. The chloroform extract from the leaves gave the highest antiproliferative activity (IC 50 , 8.46 μg/ml). Hexane extract from the fruits, aqueous and hexane extracts from B. javanica leaves showed low antiproliferative activities to the HTB-43 cell line with an IC 50 values >100 μg/ml. The chloroform extracts from fruits and leaves and methanol extract from fruits induced toxicity against brine shrimps with LC 50 values of 118.7 μg/ml, 512.44 μg/ml and 75.27 μg/ml respectively. It indicated that bioactive components presence in the crude extracts for its pharmacologic effects against head and neck cancer cells. Methanolic extract of Brucea javanica fruit was selected as the most effective extract to inhibit the growth of head and neck cancer cells (HTB-43) by the two different assays used. (author)

Squamous cell carcinoma presenting with trigeminal anesthesia: An uncommon presentation of head & neck cancer with unknown primary.

Science.gov (United States)

Shah, Ameer T; Dagher, Walid I; O'Leary, Miriam A; Wein, Richard O

The differential diagnosis of facial anesthesia is vast. This may be secondary to trauma, neoplasm, both intracranial and extracranial, infection, and neurologic disease. When evaluating a patient with isolated facial anesthesia, the head and neck surgeon often thinks of adenoid cystic carcinoma, which has a propensity for perineural invasion and spread. When one thinks of head and neck squamous cell carcinoma with or without unknown primary, the typical presentation involves dysphagia, odynophagia, weight loss, hoarseness, or more commonly, a neck mass. Squamous cell carcinoma presenting as facial anesthesia and perineural spread, with no primary site is quite rare. Case presentations and review of the literature. Trigeminal anesthesia is an uncommon presentation of head and neck squamous cell carcinoma with unknown primary. We present two interesting cases of invasive squamous cell carcinoma of the trigeminal nerve, with no primary site identified. We will also review the literature of head and neck malignancies with perineural spread and the management techniques for the two different cases presented. Copyright © 2016 Elsevier Inc. All rights reserved.

Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck

OpenAIRE

Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

2015-01-01

Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and...

14-3-3 zeta is a molecular target in guggulsterone induced apoptosis in Head and Neck cancer cells

International Nuclear Information System (INIS)

Macha, Muzafar A; Matta, Ajay; Chauhan, SS; Siu, KW Michael; Ralhan, Ranju

2010-01-01

The five-year survival rates for head and neck squamous cell carcinoma (HNSCC) patients are less than 50%, and the prognosis has not improved, despite advancements in standard multi-modality therapies. Hence major emphasis is being laid on identification of novel molecular targets and development of multi-targeted therapies. 14-3-3 zeta, a multifunctional phospho-serine/phospho-threonine binding protein, is emerging as an effector of pro-survival signaling by binding to several proteins involved in apoptosis (Bad, FKHRL1 and ASK1) and may serve as an appropriate target for head and neck cancer therapy. Herein, we determined effect of guggulsterone (GS), a farnesoid X receptor antagonist, on 14-3-3 zeta associated molecular pathways for abrogation of apoptosis in head and neck cancer cells. Head and neck cancer cells were treated with guggulsterone (GS). Effect of GS-treatment was evaluated using cell viability (MTT) assay and apoptosis was verified by annexin V, DNA fragmentation and M30 CytoDeath antibody assay. Mechanism of GS-induced apoptosis was determined by western blotting and co-IP assays using specific antibodies. Using in vitro models of head and neck cancer, we showed 14-3-3 zeta as a key player regulating apoptosis in GS treated SCC4 cells. Treatment with GS releases BAD from the inhibitory action of 14-3-3 zeta in proliferating HNSCC cells by activating protein phosphatase 2A (PP2A). These events initiate the intrinsic mitochondrial pathway of apoptosis, as revealed by increased levels of cytochrome c in cytoplasmic extracts of GS-treated SCC4 cells. In addition, GS treatment significantly reduced the expression of anti-apoptotic proteins, Bcl-2, xIAP, Mcl1, survivin, cyclin D1 and c-myc, thus committing cells to apoptosis. These events were followed by activation of caspase 9, caspase 8 and caspase 3 leading to cleavage of its downstream target, poly-ADP-ribose phosphate (PARP). GS targets 14-3-3 zeta associated cellular pathways for reducing

Selective blockade of B7-H3 enhances antitumour immune activity by reducing immature myeloid cells in head and neck squamous cell carcinoma.

Science.gov (United States)

Mao, Liang; Fan, Teng-Fei; Wu, Lei; Yu, Guang-Tao; Deng, Wei-Wei; Chen, Lei; Bu, Lin-Lin; Ma, Si-Rui; Liu, Bing; Bian, Yansong; Kulkarni, Ashok B; Zhang, Wen-Feng; Sun, Zhi-Jun

2017-09-01

Immature myeloid cells including myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs) promote tumour growth and metastasis by facilitating tumour transformation and angiogenesis, as well as by suppressing antitumour effector immune responses. Therefore, strategies designed to reduce MDSCs and TAMs accumulation and their activities are potentially valuable therapeutic goals. In this study, we show that negative immune checkpoint molecule B7-H3 is significantly overexpressed in human head and neck squamous cell carcinoma (HNSCC) specimen as compared with normal oral mucosa. Using immunocompetent transgenic HNSCC models, we observed that targeting inhibition of B7-H3 reduced tumour size. Flow cytometry analysis revealed that targeting inhibition of B7-H3 increases antitumour immune response by decreasing immunosuppressive cells and promoting cytotoxic T cell activation in both tumour microenvironment and macroenvironment. Our study provides direct in vivo evidence for a rationale for B7-H3 blockade as a future therapeutic strategy to treat patients with HNSCC. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck

Science.gov (United States)

Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

2015-01-01

Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and molecular features, and better prognosis as compared to HPV-negative carcinomas. They also possess the potential for prevention by using vaccination. The present review describes in detail the salient features of HPV associated oral squamous cell carcinoma (OSCC), its differences from HPV-negative OSCC, diagnostic features, and recent strategies in prevention and management. PMID:26483987

Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck.

Science.gov (United States)

Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

2015-01-01

Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and molecular features, and better prognosis as compared to HPV-negative carcinomas. They also possess the potential for prevention by using vaccination. The present review describes in detail the salient features of HPV associated oral squamous cell carcinoma (OSCC), its differences from HPV-negative OSCC, diagnostic features, and recent strategies in prevention and management.

Examination of the protective roles of helmet/faceshield and directionality for human head under blast waves.

Science.gov (United States)

Sarvghad-Moghaddam, Hesam; Jazi, Mehdi Salimi; Rezaei, Asghar; Karami, Ghodrat; Ziejewski, Mariusz

2015-01-01

A parametric study was conducted to delineate the efficacy of personal protective equipment (PPE), such as ballistic faceshields and advanced combat helmets, in the case of a blast. The propagations of blast waves and their interactions with an unprotected head, a helmeted one, and a fully protected finite element head model (FEHM) were modeled. The biomechanical parameters of the brain were recorded when the FEHM was exposed to shockwaves from the front, back, top, and bottom. The directional dependent tissue response of the brain and the variable efficiency of PPE with respect to the blast orientation were two major results of this study.

Post-therapeutic surveillance strategies in head and neck squamous cell carcinoma

NARCIS (Netherlands)

Digonnet, Antoine; Hamoir, Marc; Andry, Guy; Haigentz, Missak; Takes, Robert P.; Silver, Carl E.; Hartl, Dana M.; Strojan, Primoz; Rinaldo, Alessandra; de Bree, Remco; Dietz, Andreas; Gregoire, Vincent; Paleri, Vinidh; Langendijk, Johannes A.; Vander Poorten, Vincent; Hinni, Michael L.; Rodrigo, Juan P.; Suarez, Carlos; Mendenhall, William M.; Werner, Jochen A.; Genden, Eric M.; Ferlito, Alfio

The management of head and neck squamous cell carcinomas does not end with the completion of ablative therapy. The oncologic objectives of post-treatment follow-up are to detect recurrences and second primary tumors; beyond that, follow-up should evaluate acute and chronic treatment-related side

Immunocompromised and immunocompetent mouse models for head and neck squamous cell carcinoma

Directory of Open Access Journals (Sweden)

Lei ZG

2016-01-01

Full Text Available Zhen-ge Lei,1,* Xiao-hua Ren,2,* Sha-sha Wang,3 Xin-hua Liang,3,4 Ya-ling Tang3,5 1Department of Oral and Maxillofacial Surgery, Stomatological Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, 2Department of Stomatology, Sichuan Medical Science Academy and Sichuan Provincial People’s Hospital, 3State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 4Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, 5Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Abstract: Mouse models can closely mimic human oral squamous epithelial carcinogenesis, greatly expand the in vivo research possibilities, and play a critical role in the development of diagnosis, monitoring, and treatment of head and neck squamous cell carcinoma. With the development of the recent research on the contribution of immunity/inflammation to cancer initiation and progression, mouse models have been divided into two categories, namely, immunocompromised and immunocompetent mouse models. And thus, this paper will review these two kinds of models applied in head and neck squamous cell carcinoma to provide a platform to understand the complicated histological, molecular, and genetic changes of oral squamous epithelial tumorigenesis. Keywords: head and neck squamous cell carcinoma, HNSCC, mouse models, immunocompromised models, immunocompetent models, transgenic models

Radiotherapy plus cetuximab for the squamous cells carcinoma of head and neck

International Nuclear Information System (INIS)

Bonner, James A.; Harari, Paul M.; Giralt, Jordi; Azarnia, Nozar; Shin, Dong M.; Cohen, Roger B.; Jones, Cristopher U.; Sur, Ranjan; Raben, David; Jassem, Jacek; Ove, Roger; Kies, Merrill S.; Baselga, Jose; Youssoufian, Hagop; Amellal, Nadia; Rowinsky, Eric K.; Ang, K. Kian

2006-01-01

A multinational randomized study was realized, to compare radiotherapy alone with radiotherapy combined with cetuximab, a monoclonal antibody against the receiver epidermal growth factor in the treatment of squamous cell carcinoma of head and neck locally advanced [es

Current state and future of photodynamic therapy for the treatment of head and neck squamous cell carcinoma

Directory of Open Access Journals (Sweden)

Christina Mimikos

2016-06-01

Full Text Available Photodynamic therapy has shown promise in the treatment of early head and neck squamous cell carcinoma (SCC. In photodynamic therapy (PDT, a light sensitive drug (photosensitizer and visible light cause cancer cell death by the creation of singlet oxygen and free radicals, inciting an immune response, and vascular collapse. In this paper, we review several studies that demonstrate the effectiveness of PDT in the treatment of early stage SCC of the head and neck, with some showing a similar response rate to surgery. Two cases are presented to illustrate the effectiveness of PDT. Then, new advances are discussed including the discovery of STAT3 crosslinking as a potential biomarker for PDT response and interstitial PDT for locally advanced cancers. Keywords: Photodynamic therapy, PDT, Squamous cell carcinoma, Head and neck cancer

Squamous cell carcinoma antigen in serum for monitoring of head and neck and uterine cervical squamous cell carcinomas after radiotherapy

International Nuclear Information System (INIS)

Shirato, Hiroki; Ichimura, Wataru; Wakushima, Hiroshi; Nishioka, Takashi; Suzuki, Keishiro

1993-01-01

Squamous cell carcinoma antigen (SCC-A) in serum was serially measured during follow-up of 96 squamous cell carcinoma patients (75 head and neck cancers and 21 uterine cervical cancers), treated with radiotherapy. In 27 of the patients with head and neck cancer and in 12 of those with cervical cancer SCC-A had also been measured before radiotherapy. In this head and neck carcinoma group, the median level of SCC-A was 1.3 (95% CI: 1.2-1.9) ng/ml before radiotherapy and 1.4 (CI: 1.1-1.5) ng/ml after radiotherapy. In the cervical carcinoma group, the median SCC-A decreased significantly (p<0.001) from a pretreatment value of 7.5 (CI: 3.8-26.3) ng/ml to a posttreatment value of 0.9 (CI:<0.5-1.8) ng/ml. In the total group of 75 head and neck cancers 21 relapses occurred and in 4 of these the relapse was detected at a clinically silent stage by an elevation of serum SCC-A. The same was true for 4 of the 9 relapses that occurred in the total group of uterine cervical cancer. The study suggests that serum SCC-A may be useful for posttreatment monitoring of patients with uterine cervix cancer while its value in head and neck cancer probably is more marginal. (orig.)

miR-204 inhibits angiogenesis and promotes sensitivity to cetuximab in head and neck squamous cell carcinoma cells by blocking JAK2-STAT3 signaling.

Science.gov (United States)

Wu, Qingwei; Zhao, Yingying; Wang, Peihua

2018-03-01

This study aims to investigate the roles of miR-204 in tumor angiogenesis of head and neck squamous cell carcinoma (HNSCC). Here, we found that miR-204 level was reduced in HNSCC tissues relative to that in normal adjacent tissues. Overexpression of miR-204 promoted tumor angiogenesis in HNSCC cells. Mechanistically, JAK2 was identified as a direct target of miR-204, and miR-204 overexpression blocked JAK2/STAT3 pathway. Moreover, overexpression of JAK2 attenuated the inhibition of miR-204 on tumor angiogenesis of HNSCC. Furthermore, overexpression of miR-204 enhanced sensitivity of cetuximab in HNSCC cells, this effect was attenuated by JAK2 overexpression too. Importantly, JAK2 expression was negatively correlated with miR-204 level in HNSCC tissues. Therefore, miR-204 acts as a tumor suppressor by blocking JAK2/STAT3 pathway in HNSCC cells. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

General principles for treatment planning for squamous cell carcinoma of the head and neck

International Nuclear Information System (INIS)

Million, R.R.; Bova, F.J.

1987-01-01

Although squamous cell carcinoma of the head and neck represents only 5% of all malignancies, the head and neck area is one of the few anatomical areas remaining where radiotherapy is often used as the only modality for cure and often with substantial doses. There are at least 35 separate anatomical sites for origin of squamous cell carcinoma in the upper respiratory tract, and each site has its own distinctive pattern of spread, incidence of regional and distant metastases, and varying stages of presentation. It would be impossible in this short chapter to cover every contingency for treatment planning, and only general principles are outlined

Regulatory T cells and their prognostic value for patients with squamous cell carcinoma of the head and neck

Czech Academy of Sciences Publication Activity Database

Bouček, Jan; Mrkvan, Tomáš; Chovanec, M.; Kuchař, M.; Betka, Jaroslav; Bouček, V.; Hladíková, M.; Betka, J.; Eckschlager, T.; Říhová, Blanka

2010-01-01

Roč. 14, 1-2 (2010), s. 426-433 ISSN 1582-1838 R&D Projects: GA MZd NR8883; GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z50200510 Keywords : regulatory T cell s * head and neck squamous cell carcinoma * tumour markers Subject RIV: EC - Immunology Impact factor: 4.608, year: 2010

Marijuana use and increased risk of squamous cell carcinoma of the head and neck.

Science.gov (United States)

Zhang, Z F; Morgenstern, H; Spitz, M R; Tashkin, D P; Yu, G P; Marshall, J R; Hsu, T C; Schantz, S P

1999-12-01

Marijuana is the most commonly used illegal drug in the United States. In some subcultures, it is widely perceived to be harmless. Although the carcinogenic properties of marijuana smoke are similar to those of tobacco, no epidemiological studies of the relationship between marijuana use and head and neck cancer have been published. The relationship between marijuana use and head and neck cancer was investigated by a case-control study of 173 previously untreated cases with pathologically confirmed diagnoses of squamous cell carcinoma of the head and neck and 176 cancer-free controls at Memorial Sloan-Kettering Cancer Center between 1992 and 1994. Epidemiological data were collected by using a structured questionnaire, which included history of tobacco smoking, alcohol use, and marijuana use. The associations between marijuana use and head and neck cancer were analyzed by Mantel-Haenszel methods and logistic regression models. Controlling for age, sex, race, education, alcohol consumption, pack-years of cigarette smoking, and passive smoking, the risk of squamous cell carcinoma of the head and neck was increased with marijuana use [odds ratio (OR) comparing ever with never users, 2.6; 95% confidence interval (CI), 1.1-6.6]. Dose-response relationships were observed for frequency of marijuana use/day (P for trend marijuana use (P for trend marijuana use were observed with cigarette smoking, mutagen sensitivity, and to a lesser extent, alcohol use. Our results suggest that marijuana use may increase the risk of head and neck cancer with a strong dose-response pattern. Our analysis indicated that marijuana use may interact with mutagen sensitivity and other risk factors to increase the risk of head and neck cancer. The results need to be interpreted with some caution in drawing causal inferences because of certain methodological limitations, especially with regard to interactions.

CD147 and AGR2 expression promote cellular proliferation and metastasis of head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Sweeny, Larissa; Liu, Zhiyong; Bush, Benjamin D.; Hartman, Yolanda; Zhou, Tong; Rosenthal, Eben L.

2012-01-01

The signaling pathways facilitating metastasis of head and neck squamous cell carcinoma (HNSCC) cells are not fully understood. CD147 is a transmembrane glycoprotein known to induce cell migration and invasion. AGR2 is a secreted peptide also known to promote cell metastasis. Here we describe their importance in the migration and invasion of HNSCC cells (FADU and OSC-19) in vitro and in vivo. In vitro, knockdown of CD147 or AGR2 decreased cellular proliferation, migration and invasion. In vivo, knockdown of CD147 or AGR2 expression decreased primary tumor growth as well as regional and distant metastasis. -- Highlights: ► We investigated AGR2 in head and neck squamous cell carcinoma for the first time. ► We explored the relationship between AGR2 and CD147 for the first time. ► AGR2 and CD147 appear to co-localize in head and squamous cell carcinoma samples. ► Knockdown of both AGR2 and CD147 reduced migration and invasion in vitro. ► Knockdown of both AGR2 and CD147 decreased metastasis in vivo.

Direct Methanol Fuel Cell, DMFC

Directory of Open Access Journals (Sweden)

Amornpitoksuk, P.

2003-09-01

Full Text Available Direct Methanol Fuel Cell, DMFC is a kind of fuel cell using methanol as a fuel for electric producing. Methanol is low cost chemical substance and it is less harmful than that of hydrogen fuel. From these reasons it can be commercial product. The electrocatalytic reaction of methanol fuel uses Pt-Ru metals as the most efficient catalyst. In addition, the property of membrane and system designation are also effect to the fuel cell efficient. Because of low power of methanol fuel cell therefore, direct methanol fuel cell is proper to use for the energy source of small electrical devices and vehicles etc.

MicroRNAs in Head and Neck Squamous Cell Carcinoma (HNSCC) and Oral Squamous Cell Carcinoma (OSCC)

International Nuclear Information System (INIS)

Shiiba, Masashi; Uzawa, Katsuhiro; Tanzawa, Hideki

2010-01-01

MicroRNAs (miRNAs) are small, noncoding RNAs which regulate cell differentiation, proliferation, development, cell cycle, and apoptosis. Expression profiling of miRNAs has been performed and the data show that some miRNAs are upregulated or downregulated in cancer. Several studies suggest that the expression profiles of miRNAs are associated with clinical outcomes. However, the set of miRNAs with altered expressing differs depending on the type of cancer, suggesting that it is important to understand which miRNAs are related to which cancers. Therefore, this review aimed to discuss potentially crucial miRNAs in head and neck squamous cell carcinoma (HNSCC) and oral squamous cell carcinoma (OSCC)

Heads First: Visual Aftereffects Reveal Hierarchical Integration of Cues to Social Attention.

Directory of Open Access Journals (Sweden)

Sarah Cooney

Full Text Available Determining where another person is attending is an important skill for social interaction that relies on various visual cues, including the turning direction of the head and body. This study reports a novel high-level visual aftereffect that addresses the important question of how these sources of information are combined in gauging social attention. We show that adapting to images of heads turned 25° to the right or left produces a perceptual bias in judging the turning direction of subsequently presented bodies. In contrast, little to no change in the judgment of head orientation occurs after adapting to extremely oriented bodies. The unidirectional nature of the aftereffect suggests that cues from the human body signaling social attention are combined in a hierarchical fashion and is consistent with evidence from single-cell recording studies in nonhuman primates showing that information about head orientation can override information about body posture when both are visible.

The potential for tumor suppressor gene therapy in head and neck cancer.

Science.gov (United States)

Birkeland, Andrew C; Ludwig, Megan L; Spector, Matthew E; Brenner, J Chad

2016-01-01

Head and neck squamous cell carcinoma remains a highly morbid and fatal disease. Importantly, genomic sequencing of head and neck cancers has identified frequent mutations in tumor suppressor genes. While targeted therapeutics increasingly are being investigated in head and neck cancer, the majority of these agents are against overactive/overexpressed oncogenes. Therapy to restore lost tumor suppressor gene function remains a key and under-addressed niche in trials for head and neck cancer. Recent advances in gene editing have captured the interest of both the scientific community and the public. As our technology for gene editing and gene expression modulation improves, addressing lost tumor suppressor gene function in head and neck cancers is becoming a reality. This review will summarize new techniques, challenges to implementation, future directions, and ethical ramifications of gene therapy in head and neck cancer.

Prognostic significance of surgical extranodal extension in head and neck squamous cell carcinoma patients.

Science.gov (United States)

Matsumoto, Fumihiko; Mori, Taisuke; Matsumura, Satoko; Matsumoto, Yoshifumi; Fukasawa, Masahiko; Teshima, Masanori; Kobayashi, Kenya; Yoshimoto, Seiichi

2017-08-01

Lymph node metastasis with extranodal extension represents one of the most important adverse prognostic factors for survival in patients with head and neck squamous cell carcinoma. We propose that extranodal extension occurs to differing extents. The aim of this study was to determine the prognostic significance of extranodal extension in patients with head and neck squamous cell carcinoma. Two hundred and ninety-eight patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection were included. Cervical lymph nodes were classified into four categories: (i) pathological N negative, (ii) extranodal extension negative, (iii) non-surgical extranodal extension and (iv) surgical extranodal extension. Lymph node metastases were detected in 67.1% of laryngeal/hypopharyngeal cancer patients and 52.7% of oral cancer patients. The 3-year disease-specific survival rates for patients in the pathological N negative, extranodal extension negative, non-surgical extranodal extension and surgical extranodal extension groups were 90.9%, 79.6%, 63.8% and 48.3%, respectively. In laryngeal/hypopharyngeal cancer patients, surgical extranodal extension was associated with a significantly poorer disease-specific survival than a pathological N negative, extranodal extension negative or non-surgical extranodal extension status. In oral cancer patients, no significant differences were observed between the non-surgical and surgical extranodal extension groups. However, non-surgical extranodal extension was associated with a poorer disease-specific survival than a pathological N negative or extranodal extension negative status. Surgical extranodal extension was a poor prognostic factor in patients with head and neck squamous cell carcinoma. The prognostic significance of surgical extranodal extension differed between laryngeal/hypopharyngeal and oral cancer patients. The clinical significance of surgical extranodal extension was much greater for

Environmental tobacco smoking, mutagen sensitivity, and head and neck squamous cell carcinoma.

Science.gov (United States)

Zhang, Z F; Morgenstern, H; Spitz, M R; Tashkin, D P; Yu, G P; Hsu, T C; Schantz, S P

2000-10-01

Although active tobacco smoking has been considered a major risk factor for head and neck cancer, few studies have evaluated environmental tobacco smoke (ETS) and its interaction with mutagen sensitivity on the risk of head and neck cancer. We investigated the relationship between ETS and head and neck cancer in a case-control study of 173 previously untreated cases with pathologically confirmed diagnoses of squamous cell carcinoma of the head and neck and 176 cancer-free controls at Memorial Sloan-Kettering Cancer Center between 1992 and 1994. A structured questionnaire was used to collect ETS exposure and other covariates including a history of active tobacco smoking and alcohol use. ETS measures include a history of ETS exposure at home and at workplace. The associations between passive smoking and head and neck cancer were analyzed by Mantel-Haenszel methods and logistic regression models. Additive and multiplicative models were used to evaluate effect modifications between ETS and mutagen sensitivity. The crude odds ratio (OR) for ETS exposure was 2.8 [95% confidence intervals (CI), 1.3-6.0]. Controlling for age, sex, race, education, alcohol consumption, pack-years of cigarette smoking, and marijuana use, the risk of squamous cell carcinoma of the head and neck was increased with ETS (adjusted OR, 2.4; 95% CI, 0.9-6.8). Dose-response relationships were observed for the degree of ETS exposure; the adjusted ORs were 2.1 (95% CI, 0.7-6.1) for those with moderate exposure and 3.6 (95% CI, 1.1-11.5) for individuals with heavy exposure (P for trend = 0.025), in comparison with those who never had ETS exposures. These associations and the dose-response relationships were still present when the analysis was restricted to nonactive smoking cases and controls (crude OR, 2.2; 95% CI, 0.6-8.4). Crude odds ratios were 1.8 for those with moderate ETS exposure and 4.3 for individuals with heavy ETS exposure among nonsmoking cases and controls (P for trend = 0.008). More

The effect of whole body or total-head x irradiation of the metallophilic cells in the mice spleen

International Nuclear Information System (INIS)

Sasaki, Osamu; Matsueda, Yasutoshi; Mizuguchi, Hiroshi; Moriguchi, Kenzo; Ogata, Kunitoshi; Sugie, Tsuneto

1984-01-01

The purpose of this paper is to clarify morphological changes of the reticuloendothelial cells in the spleen following X-irradiation by Katsura's silver impregnation method. The animals used in this experiment were ddN female mice weighing 20 to 25g. The mice were given X-irradiation to the total-head (1,500R) or whole body (300R). The metallophilic cells in the spleen of control mice were of the small foamy type in the follicle, the large stellate type in the marginal metallophils, the small branching type in the marginal zone and the small foamy or round type in the red pulp, respectively. The metallophilic cells decreased immediately after whole body irradiation and the number of cells returned to normal in from 10 to 14 days. On the other hand, the number of the metallophilic cells in the follicle and the perifollicular region increased immediately after total-head X-irradiation. This state continued for several days. In the marginal zone and red pulp, the number of amoebian type cells appeared from 24 hours after irradiation and the number of cells in total-head irradiation group were more clearly distinguishable than in the whole body irradiated group. (author)

CD147 and AGR2 expression promote cellular proliferation and metastasis of head and neck squamous cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Sweeny, Larissa, E-mail: larissasweeny@gmail.com [Department of Surgery, University of Alabama, Division of Otolaryngology-Head and Neck Surgery, 1670 University Boulevard, Volker Hall G082, Birmingham, Alabama (United States); Liu, Zhiyong; Bush, Benjamin D.; Hartman, Yolanda [Department of Surgery, University of Alabama, Division of Otolaryngology-Head and Neck Surgery, 1670 University Boulevard, Volker Hall G082, Birmingham, Alabama (United States); Zhou, Tong [Department of Medicine, Division of Immunology and Rheumatology, 1825 University Boulevard, Shelby Biomedical Research Building 302, Birmingham, Alabama (United States); Rosenthal, Eben L., E-mail: oto@uab.edu [Department of Surgery, University of Alabama, Division of Otolaryngology-Head and Neck Surgery, 1670 University Boulevard, Volker Hall G082, Birmingham, Alabama (United States)

2012-08-15

The signaling pathways facilitating metastasis of head and neck squamous cell carcinoma (HNSCC) cells are not fully understood. CD147 is a transmembrane glycoprotein known to induce cell migration and invasion. AGR2 is a secreted peptide also known to promote cell metastasis. Here we describe their importance in the migration and invasion of HNSCC cells (FADU and OSC-19) in vitro and in vivo. In vitro, knockdown of CD147 or AGR2 decreased cellular proliferation, migration and invasion. In vivo, knockdown of CD147 or AGR2 expression decreased primary tumor growth as well as regional and distant metastasis. -- Highlights: Black-Right-Pointing-Pointer We investigated AGR2 in head and neck squamous cell carcinoma for the first time. Black-Right-Pointing-Pointer We explored the relationship between AGR2 and CD147 for the first time. Black-Right-Pointing-Pointer AGR2 and CD147 appear to co-localize in head and squamous cell carcinoma samples. Black-Right-Pointing-Pointer Knockdown of both AGR2 and CD147 reduced migration and invasion in vitro. Black-Right-Pointing-Pointer Knockdown of both AGR2 and CD147 decreased metastasis in vivo.

Cell-free mitochondrial DNA copy number variation in head and neck squamous cell carcinoma: A study of non-invasive biomarker from Northeast India.

Science.gov (United States)

Kumar, Manish; Srivastava, Shilpee; Singh, Seram Anil; Das, Anup Kumar; Das, Ganesh Chandra; Dhar, Bishal; Ghosh, Sankar Kumar; Mondal, Rosy

2017-10-01

Head and neck squamous cell carcinoma is the most commonly diagnosed cancer worldwide. The lifestyle, food habits, and customary practices manifest the Northeast Indian population toward higher susceptibility to develop head and neck squamous cell carcinoma. Here, we have investigated the association of smoke and smokeless tobacco, and alcohol with copy number variation of cell-free mitochondrial DNA and cell-free nuclear DNA in cases and controls. Cell-free DNA from plasma was isolated from 50 head and neck squamous cell carcinoma cases and 50 controls with informed written consent using QIAamp Circulating Nucleic Acid Kit. Real-time polymerase chain reaction was done for copy number variation in cell-free mitochondrial DNA and cell-free nuclear DNA. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic application between the two study groups using clinicopathological parameters. The levels of cell-free nuclear DNA and cell-free mitochondrial DNA of cases in association with smoke and smokeless tobacco, alcohol with smoking (p squamous cell carcinoma cases and controls, we distinguished cell-free mitochondrial DNA (cutoff: 19.84 raw Ct; sensitivity: 84%; specificity: 100%; p < 0.001) and cell-free nuclear DNA (cutoff: 463,282 genomic equivalent/mL; sensitivity: 53%; specificity: 87%; p < 0.001). The copy number variation in cases (cell-free nuclear DNA: 5451.66 genomic equivalent/mL and cell-free mitochondrial DNA: 29,103,476.15 genomic equivalent/mL) and controls (cell-free nuclear DNA: 1650.9 genomic equivalent/mL and cell-free mitochondrial DNA: 9,189,312.54 genomic equivalent/mL), respectively. Our result indicates that the cell-free mitochondrial DNA content is highly associated with smoke and smokeless tobacco, betel quid chewing, and alcohol which shows greater promises, holding the key characteristics of diagnostic biomarkers, that is, minimal invasiveness, high specificity, and sensitivity.

Use of next generation sequencing in head and neck squamous cell carcinomas

DEFF Research Database (Denmark)

Tabatabaeifar, Siavosh; Kruse, Torben A; Thomassen, Mads

2014-01-01

Head and neck squamous cell carcinoma (HNSCC) can primarily be attributed to alcohol consumption, tobacco use and infection with human papilloma virus. The heterogeneous nature of HNSCC has exposed a lack of tools for clinicians to provide more accurate prognosis. There is a need for biomarkers...

Laser-based direct-write techniques for cell printing

Energy Technology Data Exchange (ETDEWEB)

Schiele, Nathan R; Corr, David T [Biomedical Engineering Department, Rensselaer Polytechnic Institute, Troy, NY (United States); Huang Yong [Department of Mechanical Engineering, Clemson University, Clemson, SC (United States); Raof, Nurazhani Abdul; Xie Yubing [College of Nanoscale Science and Engineering, University at Albany, SUNY, Albany, NY (United States); Chrisey, Douglas B, E-mail: schien@rpi.ed, E-mail: chrisd@rpi.ed [Material Science and Engineering Department, Rensselaer Polytechnic Institute, Troy, NY (United States)

2010-09-15

Fabrication of cellular constructs with spatial control of cell location ({+-}5 {mu}m) is essential to the advancement of a wide range of applications including tissue engineering, stem cell and cancer research. Precise cell placement, especially of multiple cell types in co- or multi-cultures and in three dimensions, can enable research possibilities otherwise impossible, such as the cell-by-cell assembly of complex cellular constructs. Laser-based direct writing, a printing technique first utilized in electronics applications, has been adapted to transfer living cells and other biological materials (e.g., enzymes, proteins and bioceramics). Many different cell types have been printed using laser-based direct writing, and this technique offers significant improvements when compared to conventional cell patterning techniques. The predominance of work to date has not been in application of the technique, but rather focused on demonstrating the ability of direct writing to pattern living cells, in a spatially precise manner, while maintaining cellular viability. This paper reviews laser-based additive direct-write techniques for cell printing, and the various cell types successfully laser direct-written that have applications in tissue engineering, stem cell and cancer research are highlighted. A particular focus is paid to process dynamics modeling and process-induced cell injury during laser-based cell direct writing. (topical review)

Laser-based direct-write techniques for cell printing

International Nuclear Information System (INIS)

Schiele, Nathan R; Corr, David T; Huang Yong; Raof, Nurazhani Abdul; Xie Yubing; Chrisey, Douglas B

2010-01-01

Fabrication of cellular constructs with spatial control of cell location (±5 μm) is essential to the advancement of a wide range of applications including tissue engineering, stem cell and cancer research. Precise cell placement, especially of multiple cell types in co- or multi-cultures and in three dimensions, can enable research possibilities otherwise impossible, such as the cell-by-cell assembly of complex cellular constructs. Laser-based direct writing, a printing technique first utilized in electronics applications, has been adapted to transfer living cells and other biological materials (e.g., enzymes, proteins and bioceramics). Many different cell types have been printed using laser-based direct writing, and this technique offers significant improvements when compared to conventional cell patterning techniques. The predominance of work to date has not been in application of the technique, but rather focused on demonstrating the ability of direct writing to pattern living cells, in a spatially precise manner, while maintaining cellular viability. This paper reviews laser-based additive direct-write techniques for cell printing, and the various cell types successfully laser direct-written that have applications in tissue engineering, stem cell and cancer research are highlighted. A particular focus is paid to process dynamics modeling and process-induced cell injury during laser-based cell direct writing. (topical review)

Ectopic expression of protein kinase C-β sensitizes head and neck squamous cell carcinoma to diterpene esters.

Science.gov (United States)

Adams, Ryan A; D'Souza, Marjorie M A; Pierce, Carly J; Korica, Natasa; Wallwork, Ben; Parsons, Peter G; Panizza, Benedict; Boyle, Glen M

2015-03-01

The objective of this study was to examine the effect of specific Protein kinase C (PKC) isoform re-expression in solid malignancies, particularly head and neck squamous cell carcinoma cell lines, and the impact this may have on treatment with known activators of PKC. The constitutive expression of PKC isoforms were determined in six head and neck squamous cell carcinoma (SCC) cell lines. Cytotoxicity of the prototypic phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the novel diterpene ester PEP005 was established. Viral transduction to re-express PKCβ isoforms in two of these cell lines was performed, and its effect on the sensitivity to the compounds was quantified. Tongue and hypopharyngeal SCC cell lines were resistant to both TPA and PEP005, with the concentration required to inhibit growth by 50% (IC50) being >1,000 ng/ml. CAL-27 (tongue SCC) and FaDu (hypopharyngeal SCC) cell lines re-expressing PKCβI and -βII isoforms demonstrated IC50 of 1-5 ng/ml with TPA or PEP005. Re-expression of PKCβ in head and neck SCC cell lines leads to cells one thousand-times more sensitive to the cytotoxic effects of phorbol or diterpene esters in culture. This highlights the importance of the isoform in tumor progression and presents the potential benefit of these compounds in malignancies expressing the protein, and in combination therapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Direct hydrocarbon fuel cells

Science.gov (United States)

Barnett, Scott A.; Lai, Tammy; Liu, Jiang

2010-05-04

The direct electrochemical oxidation of hydrocarbons in solid oxide fuel cells, to generate greater power densities at lower temperatures without carbon deposition. The performance obtained is comparable to that of fuel cells used for hydrogen, and is achieved by using novel anode composites at low operating temperatures. Such solid oxide fuel cells, regardless of fuel source or operation, can be configured advantageously using the structural geometries of this invention.

Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines

Energy Technology Data Exchange (ETDEWEB)

Kotowski, Ulana; Heiduschka, Gregor; Eckl-Dorna, Julia; Kranebitter, Veronika; Stanisz, Isabella; Brunner, Markus; Lill, Claudia; Thurnher, Dietmar [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Vienna (Austria); Seemann, Rudolf [Medical University of Vienna, Departement of Cranio-, Maxillofacial- and Oral Surgery, Vienna (Austria); Schmid, Rainer [Medical University of Vienna, Department of Radiotherapy, Vienna (Austria)

2015-01-10

Cafestol is a diterpene molecule found in coffee beans and has anticarcinogenic properties. The aim of the study was to examine the effects of cafestol in head and neck squamous cell carcinoma (HNSCC) cells. Three HNSCC cell lines (SCC25, CAL27 and FaDu) were treated with increasing doses of cafestol. Then combination experiments with cisplatin and irradiation were carried out. Drug interactions and possible synergy were calculated using the combination index analysis. Clonogenic assays were performed after irradiation with 2, 4, 6 and 8 Gy, respectively, and the rate of apoptosis was measured with flow cytometry. Treatment of HNSCC cells with cafestol leads to a dose-dependent reduction of cell viability and to induction of apoptosis. Combination with irradiation shows a reduction of clonogenic survival compared to each treatment method alone. In two of the cell lines a significant additive effect was observed. Cafestol is a naturally occurring effective compound with growth-inhibiting properties in head and neck cancer cells. Moreover, it leads to a significant inhibition of colony formation. (orig.) [German] Cafestol ist ein Diterpen, das in der Kaffeebohne vorkommt und antikanzerogene Eigenschaften besitzt. Ziel der Studie war, die Wirkung von Cafestol auf Kopf-Hals-Tumorzelllinien zu untersuchen. Drei Kopf-Hals-Tumorzelllinien (SCC25, CAL27 und FaDu) wurden mit steigenden Cafestol-Dosen behandelt. Anschliessend fanden Kombinationsexperimente mit Cisplatin und Bestrahlung statt. Die Wechselwirkung zwischen den Substanzen und moegliche synergistische Wirkungen wurden mit dem Combination-Index analysiert. Koloniebildungstests wurden nach Bestrahlung mit 2, 4, 6 und 8 Gy durchgefuehrt. Apoptose wurde mittels Durchflusszytometrie gemessen. Die Behandlung der Kopf-Hals-Tumorzelllinien mit Cafestol fuehrt zu einer dosisabhaengigen Abnahme des Zellueberlebens und zur Induktion von Apoptose. Die Kombination von Cafestol mit Bestrahlung zeigt eine geringere

Improved local and regional control with radiotherapy for Merkel cell carcinoma of the head and neck.

Science.gov (United States)

Strom, Tobin; Naghavi, Arash O; Messina, Jane L; Kim, Sungjune; Torres-Roca, Javier F; Russell, Jeffery; Sondak, Vernon K; Padhya, Tapan A; Trotti, Andy M; Caudell, Jimmy J; Harrison, Louis B

2017-01-01

We hypothesized that radiotherapy (RT) would improve both local and regional control with Merkel cell carcinoma of the head and neck. A single-institution institutional review board-approved study was performed including 113 patients with nonmetastatic Merkel cell carcinoma of the head and neck. Postoperative RT was delivered to the primary tumor bed (71.7% cases) ± draining lymphatics (33.3% RT cases). Postoperative local RT was associated with improved local control (3-year actuarial local control 89.4% vs 68.1%; p = .005; Cox hazard ratio [HR] 0.18; 95% confidence interval [CI] = 0.06-0.55; p = .002). Similarly, regional RT was associated with improved regional control (3-year actuarial regional control 95.0% vs 66.7%; p = .008; Cox HR = 0.09; 95% CI = 0.01-0.69; p = .02). Regional RT played an important role for both clinical node-negative patients (3-year regional control 100% vs 44.7%; p = .03) and clinical/pathological node-positive patients (3-year regional control 90.9% vs 55.6%; p = .047). Local RT was beneficial for all patients with Merkel cell carcinoma of the head and neck, whereas regional RT was beneficial for clinical node-negative and clinical/pathological node-positive patients. © 2016 Wiley Periodicals, Inc. Head Neck 39: 48-55, 2017. © 2016 Wiley Periodicals, Inc.

Systematic biases in human heading estimation.

Directory of Open Access Journals (Sweden)

Luigi F Cuturi

Full Text Available Heading estimation is vital to everyday navigation and locomotion. Despite extensive behavioral and physiological research on both visual and vestibular heading estimation over more than two decades, the accuracy of heading estimation has not yet been systematically evaluated. Therefore human visual and vestibular heading estimation was assessed in the horizontal plane using a motion platform and stereo visual display. Heading angle was overestimated during forward movements and underestimated during backward movements in response to both visual and vestibular stimuli, indicating an overall multimodal bias toward lateral directions. Lateral biases are consistent with the overrepresentation of lateral preferred directions observed in neural populations that carry visual and vestibular heading information, including MSTd and otolith afferent populations. Due to this overrepresentation, population vector decoding yields patterns of bias remarkably similar to those observed behaviorally. Lateral biases are inconsistent with standard bayesian accounts which predict that estimates should be biased toward the most common straight forward heading direction. Nevertheless, lateral biases may be functionally relevant. They effectively constitute a perceptual scale expansion around straight ahead which could allow for more precise estimation and provide a high gain feedback signal to facilitate maintenance of straight-forward heading during everyday navigation and locomotion.

Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck

DEFF Research Database (Denmark)

Hald, Jeppe; Rasmussen, N; Claesson, Mogens Helweg

1995-01-01

Tumour-infiltrating lymphocytes (TIL) and tumours from six patients with squamous cell carcinomas of the head and neck (SCCHN) were investigated. The six tumours all expressed major histocompatibility complex (MHC) class I antigens both in vivo and as tumor cell lines grown in vitro. In addition...

Peroxiredoxin IV Protects Cells From Radiation-Induced Apoptosis in Head-and-Neck Squamous Cell Carcinoma

International Nuclear Information System (INIS)

Park, Jung Je; Chang, Hyo Won; Jeong, Eun-Jeong; Roh, Jong-Lyel; Choi, Seung-Ho; Jeon, Sea-Yuong; Ko, Gyung Hyuck; Kim, Sang Yoon

2009-01-01

Purpose: Human peroxiredoxins (Prxs) are known as a family of thiol-specific antioxidant enzymes, among which Prx-I and -II play an important role in protecting cells from irradiation-induced cell death. It is not known whether Prx-IV also protects cells from ionizing radiation (IR). Methods and Materials: To evaluate the protective role of Prx-IV in IR, we transfected full-length Prx-IV cDNA into AMC-HN3 cells, which weakly express endogenous Prx-IV, and knocked down the expression of Prx-IV with siRNA methods using AMC-HN7 cells, which express high levels of endogenous Prx-IV. Radiosensitivity profiles in these cells were evaluated using clonogenic assay, FACS analysis, cell viability, and TUNEL assay. Results: Three Prx-IV expressing clones were isolated. Prx-IV regulated intracellular reactive oxygen species (ROS) levels and made cells more resistant to IR-induced apoptosis. Furthermore, the knockdown of Prx-IV with siRNA made cells more sensitive to IR-induced apoptosis. Conclusion: The results of these studies suggest that Prx-IV may play an important role in protecting cells from IR-induced apoptosis in head-and-neck squamous cell carcinoma

Squamous cell carcinomas of the lung and of the head and neck: new insights on molecular characterization

Science.gov (United States)

Polo, Valentina; Pasello, Giulia; Frega, Stefano; Favaretto, Adolfo; Koussis, Haralabos; Conte, Pierfranco; Bonanno, Laura

2016-01-01

Squamous cell carcinomas of the lung and of the head and neck district share strong association with smoking habits and are characterized by smoke-related genetic alterations. Driver mutations have been identified in small percentage of lung squamous cell carcinoma. In parallel, squamous head and neck tumors are classified according to the HPV positivity, thus identifying two different clinical and molecular subgroups of disease. This review depicts different molecular portraits and potential clinical application in the field of targeted therapy, immunotherapy and chemotherapy personalization. PMID:26933818

Phosphoinositide Kinase-3 Status Associated With Presence or Absence of Human Papillomavirus in Head and Neck Squamous Cell Carcinomas

International Nuclear Information System (INIS)

Yarbrough, Wendell G.; Whigham, Amy; Brown, Brandee; Roach, Michael; Slebos, Robbert

2007-01-01

Purpose: To investigate phosphoinositide kinase-3 (PI3K) activation in relation to human papillomavirus (HPV) status in head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Gene expression microarray data were analyzed to determine differentially expressed genes between HPV(+) and HPV(-) HNSCC. PIK3CA gene expression was confirmed by quantitative reverse transcriptase-polymerase chain reaction in seven HPV(+) and seven HPV(-) primary HNSCCs. PIK3CA mutation status in three HPV(+) and nine HPV(-) cell lines was determined by polymerase chain reaction amplification of hot spot exons (1, 9, 20) followed by direct sequencing. Results: PIK3CA was overexpressed in HPV(+)-associated HNSCC compared with the expression in HPV(-) HNSCC. Activation of PIK3CA by mutation was found in 1 of the 12 tested HNSCC cell lines. Conclusion: Activation of PI3K by mutation of PIK3CA is rare in HNSCC cell lines and was not found in three HPV(+) cell lines. One mechanism by which HPV-associated HNSCC might activate PI3K is increased expression of PIK3CA

Significant Wave Heights, Periods, and Directions, and Air and Sea Temperature Data from a Directional Waverider Buoy off Diamond Head, Oahu during March-April 2000 (NODC Accession 0000475)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — A directional waverider buoy located about one nautical mile south of Diamond Head, Oahu, provided an approximately 10-day time series of wave characteristics and...

Cetuximab in locally advanced head-and-neck cancer: defining the population

Science.gov (United States)

Ho, C.

2010-01-01

Encouraging data for targeted therapy in head-and-neck squamous cell carcinoma are opening new options for treatment. Phase III trials of cetuximab, an antibody directed against the epidermal growth factor receptor (egfr) have demonstrated benefit in the locally advanced and metastatic settings. Recognizing the importance of emerging therapies, Cancer Care Ontario published guideline recommendations for egfr-targeted therapy in stage iii and iv head-and-neck cancer. The present paper takes a further look at the population for whom an offer of cetuximab therapy may be appropriate. PMID:20697514

Direct hits to the head during amateur boxing is associated with a rise in serum biomarkers for brain injury.

Science.gov (United States)

Graham, M R; Myers, T; Evans, P; Davies, B; Cooper, S M; Bhattacharya, K; Grace, F M; Baker, J S

2011-01-01

Boxing exposes participants to the physiological response to high intensity exercise and also to direct body and brain trauma. Amateur boxing is increasing and females have also been included in the Olympics. The aim of this study is to assess the stress response and possible brain injury incurred during a match by measuring serum biomarkers associated with stress and cellular brain injury before and after combat. Sixteen male amateur boxers were studied retrospectively. The study population was divided into two groups: (a) a group that received predominantly punches to the head (PTH) and (b) a group that received predominantly punches to the body (PTB). Blood samples were taken before and five minutes after each contest. They were analysed for S-100B, neuron-specific enolase (NSE), creatine kinase (CK) and cortisol. The PTH group received direct contacts to the head (not blocked, parried or avoided) and to the body (n=8, age: 17.6 ± 5.3, years; height: 1.68 ± 0.13, meters; mass: 65.4 ± 20.3, kg). The PTB group received punches to the body including blocked and parried punches, but received no direct punches to the head, (n=8, mean ± SD, age: 19.1 ± 3.2 years; height: 1.70 ± 0.75, meters; mass: 68.5 ± 15 kg). Significant increases (P<0.05) were observed between pre- and post-combat serum concentrations in serum concentrations in PTH of S-100B (0.35 ± 0.61 vs. 0.54 ± 0.73, μg.L-1) NSE (19.7 ± 14 vs.31.1 ± 26.6, ng.ml-1) and cortisol (373 ± 202 vs. 756 ± 93, nmol.L-1). Significant increases (P<0.05) of creatine kinase were recorded in both groups. This study demonstrates significant elevations in neurochemical biomarkers in boxers who received direct blows to the head. However, further work is required to quantify this volumetric brain damage and long term clinical sequelae.

Cytogenetic damage in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients undergoing radiotherapy

International Nuclear Information System (INIS)

Minicucci, E.M.; Ribeiro, L.R.; Camargo, J.L.V. de; Salvadori, D.M.F.

2005-01-01

This study evaluated cytogenetic damage by measuring the frequency of micronucleated cells (MNC) in peripheral blood and buccal mucosa of head-and-neck cancer patients undergoing radiotherapy. MNC frequencies were assessed in 31 patients before, during, and after radiotherapy, and in 17 healthy controls matched for gender, age, and smoking habits. Results showed no statistically significant difference between patients and controls prior to radiotherapy in cytokinesis-blocked lymphocytes or buccal mucosa cells. During treatment, increased MNC frequencies were observed in both cell types. Micronucleated lymphocyte levels remained high in samples collected 30 to 140 days after the end of treatment, while MNC frequency in buccal mucosa decreased to values statistically similar to baseline values. There is controversy over the effects of age, smoking habit, tumor stage, and/or metastasis on MNC frequency. However, increased frequency of micronucleated buccal mucosa cells was seen in patients under 60 years old and in those with tumors >4 cm. In conclusion, the data show that radiotherapy has a potent clastogenic effect in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients, and that the baseline MNC frequency in these two tissues is not a sensitive marker for head-and neck neoplasm. (author)

Silk Film Topography Directs Collective Epithelial Cell Migration

Science.gov (United States)

Rosenblatt, Mark I.

2012-01-01

The following study provides new insight into how surface topography dictates directed collective epithelial cell sheet growth through the guidance of individual cell movement. Collective cell behavior of migrating human corneal limbal-epithelial cell sheets were studied on highly biocompatible flat and micro-patterned silk film surfaces. The silk film edge topography guided the migratory direction of individual cells making up the collective epithelial sheet, which resulted in a 75% increase in total culture elongation. This was due to a 3-fold decrease in cell sheet migration rate efficiency for movement perpendicular to the topography edge. Individual cell migration direction is preferred in the parallel approach to the edge topography where localization of cytoskeletal proteins to the topography’s edge region is reduced, which results in the directed growth of the collective epithelial sheet. Findings indicate customized biomaterial surfaces may be created to direct both the migration rate and direction of tissue epithelialization. PMID:23185573

Combined inhibition of EMMPRIN and epidermal growth factor receptor prevents the growth and migration of head and neck squamous cell carcinoma cells.

Science.gov (United States)

Suzuki, Shinsuke; Ishikawa, Kazuo

2014-03-01

It has been reported that the epidermal growth factor receptor (EGFR) expression is associated with the extracellular matrix metalloproteinase inducer (EMMPRIN) in some solid tumors; however, the relationship of EMMPRIN with EGFR in head and neck cancers is not fully understood. To determine the relationship between EMMPRIN and EGFR in head and neck squamous cell carcinoma (HNSCC), HNSCC cells were stimulated with epidermal growth factor (EGF), a ligand of EGFR. EMMPRIN expression in HNSCC cells was upregulated by EGF. In addition, EGF stimulation induced HNSCC cell invasion and MMP-9 expression. This increase in invasion and MMP-9 expression was abrogated by downmodulation of EMMPRIN. Furthermore, to determine the effects of combined EMMPRIN and EGFR targeting in HNSCC, HNSCC cells were treated with an EMMPRIN function-blocking antibody and the EGFR inhibitor AG1478. This combined treatment resulted in greater inhibition of HNSCC cell proliferation and migration compared with the individual agents alone. These results suggest that EMMPRIN mediates EGFR-induced tumorigenicity and that combined targeting of EMMPRIN and EGFR may be an efficacious treatment approach.

Early processing variations in selective attention to the color and direction of moving stimuli during 30 days head-down bed rest

Science.gov (United States)

Wang, Lin-Jie; He, Si-Yang; Niu, Dong-Bin; Guo, Jian-Ping; Xu, Yun-Long; Wang, De-Sheng; Cao, Yi; Zhao, Qi; Tan, Cheng; Li, Zhi-Li; Tang, Guo-Hua; Li, Yin-Hui; Bai, Yan-Qiang

2013-11-01

Dynamic variations in early selective attention to the color and direction of moving stimuli were explored during a 30 days period of head-down bed rest. Event-related potentials (ERPs) were recorded at F5, F6, P5, P6 scalp locations in seven male subjects who attended to pairs of bicolored light emitting diodes that flashed sequentially to produce a perception of movement. Subjects were required to attend selectively to a critical feature of the moving target, e.g., color or direction. The tasks included: a no response task, a color selective response task, a moving direction selective response task, and a combined color-direction selective response task. Subjects were asked to perform these four tasks on: the 3rd day before bed rest; the 3rd, 15th and 30th day during the bed rest; and the 5th day after bed rest. Subjects responded quickly to the color than moving direction and combined color-direction response. And they had a longer reaction time during bed rest on the 15th and 30th day during bed rest after a relatively quicker response on the 3rd day. Using brain event-related potentials technique, we found that in the color selective response task, the mean amplitudes of P1 and N1 for target ERPs decreased in the 3rd day during bed rest and 5th day after bed rest in comparison with pre-bed rest, 15th day and 30th day during bed rest. In the combined color-direction selective response task, the P1 latencies for target ERPs on the 3rd and 30th day during bed rest were longer than on the 15th day during bed rest. As 3rd day during bed rest was in the acute adaptation period and 30th day during bed rest was in the relatively adaptation stage of head-down bed rest, the results help to clarify the effects of bed rest on different task loads and patterns of attention. It was suggested that subjects expended more time to give correct decision in the head-down tilt bed rest state. A difficulty in the recruitment of brain resources was found in feature selection task

Direction-Specific Impairments in Cervical Range of Motion in Women with Chronic Neck Pain: Influence of Head Posture and Gravitationally Induced Torque.

Science.gov (United States)

Rudolfsson, Thomas; Björklund, Martin; Svedmark, Åsa; Srinivasan, Divya; Djupsjöbacka, Mats

2017-01-01

Cervical range of motion (ROM) is commonly assessed in clinical practice and research. In a previous study we decomposed active cervical sagittal ROM into contributions from lower and upper levels of the cervical spine and found level- and direction-specific impairments in women with chronic non-specific neck pain. The present study aimed to validate these results and investigate if the specific impairments can be explained by the neutral posture (defining zero flexion/extension) or a movement strategy to avoid large gravitationally induced torques on the cervical spine. Kinematics of the head and thorax was assessed in sitting during maximal sagittal cervical flexion/extension (high torque condition) and maximal protraction (low torque condition) in 120 women with chronic non-specific neck pain and 40 controls. We derived the lower and upper cervical angles, and the head centre of mass (HCM), from a 3-segment kinematic model. Neutral head posture was assessed using a standardized procedure. Previous findings of level- and direction-specific impairments in neck pain were confirmed. Neutral head posture was equal between groups and did not explain the direction-specific impairments. The relative magnitude of group difference in HCM migration did not differ between high and low torques conditions, lending no support for our hypothesis that impairments in sagittal ROM are due to torque avoidance behaviour. The direction- and level-specific impairments in cervical sagittal ROM can be generalised to the population of women with non-specific neck pain. Further research is necessary to clarify if torque avoidance behaviour can explain the impairments.

Direction-Specific Impairments in Cervical Range of Motion in Women with Chronic Neck Pain: Influence of Head Posture and Gravitationally Induced Torque.

Directory of Open Access Journals (Sweden)

Thomas Rudolfsson

Full Text Available Cervical range of motion (ROM is commonly assessed in clinical practice and research. In a previous study we decomposed active cervical sagittal ROM into contributions from lower and upper levels of the cervical spine and found level- and direction-specific impairments in women with chronic non-specific neck pain. The present study aimed to validate these results and investigate if the specific impairments can be explained by the neutral posture (defining zero flexion/extension or a movement strategy to avoid large gravitationally induced torques on the cervical spine.Kinematics of the head and thorax was assessed in sitting during maximal sagittal cervical flexion/extension (high torque condition and maximal protraction (low torque condition in 120 women with chronic non-specific neck pain and 40 controls. We derived the lower and upper cervical angles, and the head centre of mass (HCM, from a 3-segment kinematic model. Neutral head posture was assessed using a standardized procedure.Previous findings of level- and direction-specific impairments in neck pain were confirmed. Neutral head posture was equal between groups and did not explain the direction-specific impairments. The relative magnitude of group difference in HCM migration did not differ between high and low torques conditions, lending no support for our hypothesis that impairments in sagittal ROM are due to torque avoidance behaviour.The direction- and level-specific impairments in cervical sagittal ROM can be generalised to the population of women with non-specific neck pain. Further research is necessary to clarify if torque avoidance behaviour can explain the impairments.

Stereotactic Body Radiotherapy for Head and Neck Tumors

Science.gov (United States)

2016-04-18

Squamous Cell Carcinoma of the Head and Neck; Nasopharyngeal Carcinoma; Salivary Gland Cancer; Head and Neck Sarcoma; Paraganglioma of Head and Neck; Chordoma of Head and Neck; Chondrosarcoma of Head and Neck; Angiofibroma of Head and Neck

Radioresistant head and neck squamous cell carcinoma cells: Intracellular signaling, putative biomarkers for tumor recurrences and possible therapeutic targets

International Nuclear Information System (INIS)

Skvortsov, Sergej; Jimenez, Connie R.; Knol, Jaco C.; Eichberger, Paul; Schiestl, Bernhard; Debbage, Paul; Skvortsova, Ira; Lukas, Peter

2011-01-01

Purpose: Treatment of local and distant head and neck cancer recurrences after radiotherapy remains an unsolved problem. In order to identify potential targets for use in effective therapy of recurrent tumors, we have investigated protein patterns in radioresistant (FaDu-IRR and SCC25-IRR, “IRR cells”) as compared to parental (FaDu and SCC25) head and neck carcinoma cells. Methods and materials: Radiation resistant IRR cells were derived from parental cells after repeated exposure to ionizing radiation 10 times every two weeks at a single dose of 10 Gy, resulting in a total dose of 100 Gy. Protein profiling in parental and IRR cells was carried out using two-dimensional differential gel electrophoresis (2D-DIGE) followed by MALDI-TOF/TOF mass spectrometry. Cell viability, cell migration assays and Western blot analysis were used to confirm results obtained using the proteome approach. Results: Forty-five proteins that were similarly modulated in FaDu-IRR and SCC25-IRR cells compared to parental cells were selected to analyze their common targets. It was found that these either up- or down-regulated proteins are closely related to the enhancement of cell migration which is regulated by Rac1 protein. Further investigations confirmed that Rac1 is up-regulated in IRR cells, and inhibiting its action reduces the migratory abilities of these cells. Additionally, the Rac1 inhibitor exerts cytostatic effects in HNSCC cells, mostly in migratory cells. Conclusions: Based on these results, we conclude that radioresistant HNSCC cells possess enhanced metastatic abilities that are regulated by a network of migration-related proteins. Rac1 protein may be considered as a putative biomarker of HNSCC radiation resistance, and as a potential therapeutic target for treating local and distant HNSCC recurrences.

SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK: NEW AVENUES OF TREATMENT?

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T. Braunschweig

2013-01-01

Full Text Available Squamous cell carcinoma of the head and neck counts for 3 % of all cancers in men and half of this number less in women with a 5-year survival of 61 %. While the number of laryngeal carcinoma is decreasing, carcinoma of the oral cavity related to an infection by the human papilloma virus (HPV, high-risk subtypes is increasing, especially in younger patients. HPV related squamous cell carcinomas show better survival data, especially in regard to recurrence free rates or secondary carcinoma of adjacent locations. Squamous cell carcinomas related to the presence of HPV DNA material is almost exclusively found in carcinoma of the oral cavity and oropharyngeal mucosa. Much less frequently HPV is present in hypopharyngeal carcinomas and even less number of cases of squamous cell carcinoma with proof for HPV in the nasopharynx and larynx. In case of evidence for HPV DNA; most cases are positively tested for subtype 16, followed by subtype 18. As a surrogate immunhistochemical marker, p16 INK4A is stained positive, cytoplasmic and nuclear. In a small study by ourselves, we found a positive correlation in 100 % of p16 INK4A positivity and positive HPV testing. Oral squamous cell carcinoma is more frequently related to HPV in patients below 50 years of age with a prevalence of ca. 20 %. Whilst HPV high-risk positive carcinomas show very few mutations in single signalling molecules of the downstream receptor tyrosin kinase pathways, HPV negative carcinomas show in many cases a chaotic DNA mutation type with typical mutations in tumor suppressor genes, as p53 and CDKN2A. This pattern is often seen in carcinoma types develop from a summation of accidental mutations often caused by toxins (e.g. inhaled cigarette smoke. However, it is discussed and under investigation whether a subset of head and neck squamous cell carcinomasdevelop from so called driver mutations, as are called mutations in critical members of signalling pathways and receptor tyrosin kinases

Posture, head stability, and orientation recovery during vestibular regeneration in pigeons.

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Dickman, J David; Lim, Insook

2004-09-01

Compensatory behavior such as oculomotor, gaze, and postural responses that occur during movement largely depend upon a functioning vestibular system. In the present study, the initial loss and subsequent recovery of postural and head stability in pigeons undergoing vestibular regeneration were examined. Adult pigeons were trained to manipulate a straight run chamber to peck an illuminated key for fluid reward. Six behavioral measures assessing performance, posture, and head stability were quantified. These included run latency, steps (walking), path negotiation (lane changes), gaze saccades, head bobs, and head shakes. Once normative values were obtained for four birds, complete lesion of all receptor cells and denervation of the epithelia in the vestibular endorgans were produced using a single intralabyrinthine application of streptomycin sulfate. Each bird was then tested at specific times during regeneration and the same behavioral measures examined. At 7 days post-streptomycin treatment (PST), all birds exhibited severe postural and head instability, with tremors, head shakes, staggering, and circling predominating. No normal trial runs, walking, gaze saccades, or head bobs were present. Many of these dysfunctions persisted through 3-4 weeks PST. Gradually, tremor and head shakes diminished and were replaced with an increasing number of normal head bobs during steps and gaze saccades. Beginning at 4 weeks PST, but largely inaccurate, was the observed initiation of directed steps, less staggering, and some successful path negotiation. As regeneration progressed, spatial orientation and navigation ability increased and, by 49 days PST, most trials were successful. By 70 days PST, all birds had recovered to pretreatment levels. Thus, it was observed that ataxia must subside, coincident with normalized head and postural stability prior to the recovery of spatial orientation and path navigation recovery. Parallels in recovery were drawn to hair cell regeneration

Radiosensitization of head/neck sqaumous cell carcinoma by adenovirus-mediated expression of the Nbs1 protein

International Nuclear Information System (INIS)

Rhee, Juong G.; Li, Daqing; Suntharalingam, Mohan; Guo Chuanfa; O'Malley, Bert W.; Carney, James P.

2007-01-01

Purpose: Local failure and toxicity to adjacent critical structures is a significant problem in radiation therapy of cancers of the head and neck. We are developing a gene therapy based method of sensitizing head/neck squamous cell carcinoma (HNSCC) to radiation treatment. As patients with the rare hereditary disorder, Nijmegen breakage syndrome, show radiation sensitivity we hypothesized that tumor-specific disruption of the function of the Nbs1 protein would lead to enhanced cellular sensitivity to ionizing radiation. Experimental Procedures: We constructed two recombinant adenoviruses by cloning the full-length Nbs1 cDNA as well as the C-terminal 300 amino acids of Nbs1 into an adenovirus backbone under the control of a CMV promoter. The resulting adenoviruses were used to infect HNSCC cell line JHU011. These cells were evaluated for expression of the viral based constructs and assayed for clonogenic survival following radiation exposure. Results: Exposure of cells expressing Nbs1-300 to ionizing radiation resulted in a small reduction in survival relative to cells infected with control virus. Surprisingly, expression of full-length Nbs1 protein resulted in markedly enhanced sensitivity to ionizing radiation. Furthermore, the use of a fractionated radiation scheme following virus infection demonstrates that expression of full-length Nbs1 protein results in significant reduction in cell survival. Conclusions: These results provide a proof of principle that disruption of Nbs1 function may provide a means of enhancing the radiosensitivity of head and neck tumors. Additionally, this work highlights the Mre11 complex as an attractive target for development of radiation sensitizers

Treatment of head and neck squamous cell carcinoma in elderly patients

International Nuclear Information System (INIS)

Honda, Keigo; Asato, Ryo; Tsuji, Jun; Kanda, Tomoko; Ushiro, Kohji; Watanabe, Yoshiki; Mori, Yusuke

2010-01-01

The object of this study was to clarify the characteristics of treatment for elderly head and neck squamous cell cancer patients. We conducted a chart review of 177 head and neck squamous cell cancer patients who had been treated at Kyoto Medical Center, from 2005 through 2009. All the collected data were analyzed to compare the clinical features and the treatment outcomes between the younger group ( or =75, EG, n=46). Male to female ratio was lower in EG (5.6:1 vs. 1.7:1, p<0.01). C urative treatment was performed in most of the patients with early disease (stage I-II) in both groups (96.7% vs. 90.5%), while the ratio of curative treatment was significantly lower in EG patients with advanced stage disease (stage III-IV) (92.3% vs. 52.0%, p<0.01). There was no significant difference in the frequency of adopted treatment modality (surgery or radiotherapy) between YG and EG. Adjuvant chemotherapy or postoperative radiotherapy was avoided in most of EG patients. Local complication rates after major surgery for advanced cases were similar in both groups (30.8% vs. 27.3%), while a higher systemic complication rate was observed in EG (0% vs. 27.3%). After curative treatment, there was no difference in disease specific three-year survival rates between YG and EG (100% vs. 100% in early stage disease, 65.2% vs. 60.6% in advanced disease, Kaplan-Meier curve). Although treatment of elderly patients with head and neck cancer can be inhibited by poor performance status and/or concomitant diseases, clinical results after curative treatment are comparable to those of younger patients. (author)

Effects of neratinib and combination with irradiation and chemotherapy in head and neck cancer cells.

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Schneider, S; Thurnher, D; Kadletz, L; Seemann, R; Brunner, M; Kotowski, U; Schmid, R; Lill, C; Heiduschka, G

2016-11-01

Prognosis of patients with head and neck squamous cell carcinoma (HNSCC) is still poor. Novel therapeutic approaches are of great interest to improve the effects of radiochemotherapy. We evaluated the effects of tyrosine kinase inhibitor neratinib on HNSCC cell lines CAL27, SCC25 and FaDu as a single agent and in combination with irradiation and chemotherapy. Effects of neratinib were evaluated in HNSCC cell lines CAL27, SCC25 and FaDu. Effect on cell viability of neratinib and combination with cisplatin and irradiation was measured using CCK-8 assays and clonogenic assays. Western blot analysis was performed to distinguish the effect on epithelial growth factor receptor and HER2 expression. Apoptosis was evaluated by flow cytometry analysis. Growth inhibition was achieved in all cell lines, whereas combination of cisplatin and neratinib showed greater inhibition than each agent alone. Apoptosis was induced in all cell lines. Combination of neratinib with irradiation or cisplatin showed significantly increased apoptosis. In clonogenic assays, significant growth inhibition was observed in all investigated cell lines. Neratinib, as a single agent or in combination with chemo-irradiation, may be a promising treatment option for patients with head and neck cancer. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Incidence of Etiologic Factors in Squamous Cell Carcinoma of Head and Neck in Ahvaz

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Soheila Nikakhlagh

2011-01-01

 Conclusion: According to this study, tobacco smoking was the most important etiologic factor and had a strong effect on risk of head and neck squamous cell carcinoma. Other factors are also important and need more research study.

Leader Cells Define Directionality of Trunk, but Not Cranial, Neural Crest Cell Migration

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Jo Richardson

2016-05-01

Full Text Available Collective cell migration is fundamental for life and a hallmark of cancer. Neural crest (NC cells migrate collectively, but the mechanisms governing this process remain controversial. Previous analyses in Xenopus indicate that cranial NC (CNC cells are a homogeneous population relying on cell-cell interactions for directional migration, while chick embryo analyses suggest a heterogeneous population with leader cells instructing directionality. Our data in chick and zebrafish embryos show that CNC cells do not require leader cells for migration and all cells present similar migratory capacities. In contrast, laser ablation of trunk NC (TNC cells shows that leader cells direct movement and cell-cell contacts are required for migration. Moreover, leader and follower identities are acquired before the initiation of migration and remain fixed thereafter. Thus, two distinct mechanisms establish the directionality of CNC cells and TNC cells. This implies the existence of multiple molecular mechanisms for collective cell migration.

The effect of cilengitide in combination with irradiation and chemotherapy in head and neck squamous cell carcinoma cell lines

International Nuclear Information System (INIS)

Heiduschka, G.; Lill, C.; Schneider, S.; Kotowski, U.; Thurnher, D.; Seemann, R.; Kornek, G.; Schmid, R.

2014-01-01

Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC). The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis. Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide. Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity. (orig.) [de

Cilia in the head of hornets: form and function.

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Ishay, Jacob S; Plotkin, Marian; Ermakov, Natalya; Jongebloed, Willem L; Kalicharan, Dharamdajal; Bergman, David J

2005-06-01

In the head of the Oriental hornet, beneath the cuticle, there are plaques of hair cells. These are distributed throughout the upper front part of the head; to wit: in the region of the vertex (i.e., around and behind the ocelli), in the genae around and behind the compound eyes (the ommatidia), and in the region of the forehead or frons. These hair cells are arranged with their thin whip-like part (i.e., cilia) directed outward and morphologically fall into three distinct groups: type (a) thin elongated cilia connected to each other alongside by side-links; type (b) thin elongated cilia of which two or more interconnect at their distal ends via a delicate nerve fiber bearing a knob at its center; and type (c) shorter and thicker cilia that roughly resemble a triangular thorn and are also interconnected by a thin thread, which, however, bears a ball rather then a knob at its center. The knob in the one case and the ball in the other vary in their diameter, but in both instances the interconnecting elements, be they nerve fibers or threads, are seemingly multidirectional. Beneath the frons, in the region of the coronal suture, the hair cells (cilial plaques) are inwardly directed and bear a large trachea at their center. Presumably, the "weighted" cilial cells that are directed toward the exterior of the body aid the hornet in navigation and gravity determination whereas the inwardly directed ciliary cells may possibly serve in acoustic communication. Another element worthy of mention within the hair cells are yellow granules (yg). These yg's originate from the whip-like portion of the ciliary cells that are distributed beneath the frons plate, and also in the yellow stripes of the gastral cuticle. Conceivably, these yellow granules, in both cases, may play a role in the absorption and storage of solar energy. In summary, ciliary structures are involved in the hornet in gravity sensing, in acoustical communication and in light sensing, i.e., with some similarity

Lactoferricin B reverses cisplatin resistance in head and neck squamous cell carcinoma cells through targeting PD-L1.

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Zhang, Pei; Liu, Jinzhong; Li, Wenlu; Li, Shanshan; Han, Xinguang

2018-05-15

Head and neck squamous cell carcinoma (HNSCC) ranks among the top most common cancers with a poor prognosis. The mechanism of chemoresistance is still not well known. This study is to investigate the programmed death-ligand 1 (PD-L1) expression in HNSCC, and test the effect of lactoferricin B (LfcinB) on chemoresistance and its mechanism. We analyzed 510 HNSCC patients in TCGA database and investigated how CD274 expression was related to patient prognosis. PD-L1 was verified from HNSCC samples at local hospital with immunohistochemistry. PD-L1 expression in the acquired cisplatin-resistant HNSCC cells was examined by PCR and WB in order to test PD-L1-induced chemoresistance. LfcinB inoculation in cisplatin-resistant HNSCC cells and in the nude mice was introduced to test the effect of LfcinB on targeting cisplatin resistance and its mechanism. High CD274 mRNA (>125 FPKM) from TCGA database had a significantly reduced 5-year survival rate, and a lower 5-year survival rate in the chemotherapy and radiotherapy-treated patients (P < .05). PD-L1 overexpression was further supported from analysis of 40 HNSCC specimens. PD-L1 and IL-6 in the established cisplatin-resistant HNSCC cells were shown significantly higher (P < .05). IL-6 and PD-L1 expression were partially inhibited by the anti-IL-6/STAT3 antibody. LfcinB displayed a direct cytotoxic effect on cisplatin-resistant HNSCC cells and HNSCC xenografts of cisplatin-resistant cells in the nude mice displayed significant reduction in tumor volume after LfcinB injection (P < .05). Besides, the increase of IL-6 and PD-L1 in cisplatin-resistant HNSCC cells was abolished in vitro by LfcinB (P < .05). PD-L1 expression in HNSCC cells correlates with poor prognosis and chemoresistance, and LfcinB might provide therapeutic potential in HNSCC patients through modulating IL-6 and PD-L1. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Mesenchymal Stem Cells Induce Epithelial to Mesenchymal Transition in Colon Cancer Cells through Direct Cell-to-Cell Contact

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Hidehiko Takigawa

2017-05-01

Full Text Available We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow–derived mesenchymal stem cells (MSCs migrated to the tumor stroma and promoted tumor growth and metastasis. Here, we evaluated the proliferation and migration ability of cancer cells cocultured with MSCs to elucidate the mechanism of interaction between cancer cells and MSCs. Proliferation and migration of cancer cells increased following direct coculture with MSCs but not following indirect coculture. Thus, we hypothesized that direct contact between cancer cells and MSCs was important. We performed a microarray analysis of gene expression in KM12SM colon cancer cells directly cocultured with MSCs. Expression of epithelial-mesenchymal transition (EMT–related genes such as fibronectin (FN, SPARC, and galectin 1 was increased by direct coculture with MSCs. We also confirmed the upregulation of these genes with real-time polymerase chain reaction. Gene expression was not elevated in cancer cells indirectly cocultured with MSCs. Among the EMT-related genes upregulated by direct coculture with MSCs, we examined the immune localization of FN, a well-known EMT marker. In coculture assay in chamber slides, expression of FN was seen only at the edges of cancer clusters where cancer cells directly contacted MSCs. FN expression in cancer cells increased at the tumor periphery and invasive edge in orthotopic nude mouse tumors and human colon cancer tissues. These results suggest that MSCs induce EMT in colon cancer cells via direct cell-to-cell contact and may play an important role in colon cancer metastasis.

C2-Ceramide Induces Cell Death and Protective Autophagy in Head and Neck Squamous Cell Carcinoma Cells

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Wenyuan Zhu

2014-02-01

Full Text Available Ceramides are second messengers involved in several intracellular processes in cancer cells, amongst others. The aim of this study was to evaluate the anti-tumor efficacy of C2-ceramide (C2-Cer; N-acetyl-D-sphingosine by investigating cell death and autophagy in head and neck squamous cell carcinoma (HNSCC cells. C2-Cer showed concentration-dependent cytotoxicity in HN4 and HN30 cell lines. It simultaneously induced caspase-3-independent apoptosis and programmed necrosis. C2-Cer markedly increased the expression level of microtubule-associated protein 1 light chain 3B (LC3B type II associated with protective autophagy. An autophagy inhibitor enhanced C2-Cer-mediated cytotoxicity, while a programmed-necrosis inhibitor produced the opposite effect. Furthermore, C2-Cer up-regulated the phosphorylation of extracellular signal-regulated kinase 1/2, but down-regulated its downstream substrate phospho-mammalian target of rapamycin (p-mTOR during the autophagy process. These results suggested that C2-Cer exerts anti-tumor effects by inducing programmed apoptosis and necrosis in HNSCC, and these cytotoxic effects are enhanced by an autophagy inhibitor.

Sialic acids in squamous cell carcinoma of the head and neck

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Izabela Bronikowska

2016-12-01

Full Text Available Altered glycosylation is a universal characteristic of cancer cells, and various types of glycan structures are well‑known markers of tumor progression and invasion. The present article discusses this aspect of the role of sialic acid, biosynthesis of sialylglycoconjugates and the genetic basis of its disorder, as well as the effects and the correlation between altered sialylation and clinical prognosis in head and neck squamous cell carcinoma (HNSCC.Only a few studies concerning the level of sialic acid in head and neck tumors have been conducted so far. The conclusions of the published reports dedicated to that problem confirm the presence of elevated levels of total sialic acid in these tumors. The authors do not always agree with the level of free or associated form of sialic acid correlated with tumor size, severity of the condition, and lymph nodes. Comparing the progress that has been made in the diagnosis and treatment of other cancers thanks to extensive work on the role of sialic acids, we come to the conclusion that only further detailed studies of this subject in relation to HNSCC are able to answer the question whether the extent of glycoforms of sialic acid may act as a tumor marker or target of immunotherapy.

Lycopene inhibits the cell proliferation and invasion of human head and neck squamous cell carcinoma.

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Ye, Min; Wu, Qundan; Zhang, Min; Huang, Jinbei

2016-10-01

Lycopene has been shown to be associated with anticancer effects in numerous tumor types. However, the underlying mechanisms of lycopene in human head and neck squamous cell carcinoma (HNSCC) remain to be determined. The present study aimed to investigate the involvement of lycopene overload and the cytotoxic effects of lycopene on HNSCC cells, and to determine the possible mechanisms involved. Treatment with lycopene at a dose of >10 µM for >24 h inhibited the growth of FaDu and Cal27 cells in a time‑ and dose‑dependent manner. The clearest increase in growth inhibition was due to the apoptotic population being significantly increased. The invasion abilities decreased with 25 µM lycopene exerting significant inhibitory effects (Plycopene induced the upregulation of the pro‑apoptotic protein, B‑cell lymphoma‑associated X protein, and therefore, resulted in the inhibition of the protein kinase B and mitogen‑activated protein kinase signaling pathway. These data provided insights into the antitumor activity of lycopene in HNSCC cells.

Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: Normal tissue complication probability modeling with latent time correction

DEFF Research Database (Denmark)

Rønjom, Marianne Feen; Brink, Carsten; Bentzen, Søren

2013-01-01

To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors.......To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors....

The Role of Free Tissue Transfer in Merkel Cell Carcinoma of the Head and Neck

International Nuclear Information System (INIS)

Londino, A. V.; Miles, B. A.

2012-01-01

Merkel cell carcinoma (MCC) is an uncommon neuroendocrine malignancy with a propensity for the head and neck. It typically presents a symptomatically in elderly Caucasians and is characterized by early local and regional spread. There is currently limited data on the appropriate algorithm for treatment of MCC. However, multimodal therapy with wide surgical excision with or without radiation therapy has become standard of care. The location of the primary tumor and intensive adjuvant therapy is often required, provides a challenge to the reconstructive head and neck surgeon. Occasionally, free tissue transfer reconstructive techniques are employed in the reconstruction of MCC defects. This paper will discuss the role of free tissue transfer as a reconstructive option after surgery for advanced head and neck MCC

Immunotherapy for Head and Neck Squamous Cell Carcinoma.

Science.gov (United States)

Moskovitz, Jessica; Moy, Jennifer; Ferris, Robert L

2018-03-03

Discussion of current strategies targeting the immune system related to solid tumors with emphasis on head and neck squamous cell carcinoma (HNSCC).This review will outline the current challenges with immunotherapy and future goals for treatment using these agents. Agents targeting immune checkpoint receptors (IR) such as program death 1 (PD1) have been used in the clinical realm for melanoma and non-small cell lung cancer (NSCLC), and the use of these agents for these malignancies has provided crucial information about how and why patients respond or not to inhibitory checkpoint receptor blockade therapy (ICR). The anti PD1 agent, nivolumab, was recently approved by the FDA as a standard of care regimen for patients with platinum refractory recurrent/metastatic (R/M) HNSCC. Molecular pathways leading to resistance are starting to be identified, and work is underway to understand the most optimal treatment regimen with incorporation of immunotherapy. ICR has renewed interest in the immunology of cancer, but resistance is not uncommon, and thus understanding of these mechanisms will allow the clinician to appropriately select patients that will benefit from this therapy.

Methods of conditioning direct methanol fuel cells

Science.gov (United States)

Rice, Cynthia; Ren, Xiaoming; Gottesfeld, Shimshon

2005-11-08

Methods for conditioning the membrane electrode assembly of a direct methanol fuel cell ("DMFC") are disclosed. In a first method, an electrical current of polarity opposite to that used in a functioning direct methanol fuel cell is passed through the anode surface of the membrane electrode assembly. In a second method, methanol is supplied to an anode surface of the membrane electrode assembly, allowed to cross over the polymer electrolyte membrane of the membrane electrode assembly to a cathode surface of the membrane electrode assembly, and an electrical current of polarity opposite to that in a functioning direct methanol fuel cell is drawn through the membrane electrode assembly, wherein methanol is oxidized at the cathode surface of the membrane electrode assembly while the catalyst on the anode surface is reduced. Surface oxides on the direct methanol fuel cell anode catalyst of the membrane electrode assembly are thereby reduced.

[Lectin-binding patterns and cell kinetics of head and neck squamous cell carcinomas].

Science.gov (United States)

Gotoh, T

1991-01-01

In order to elucidate the cell characteristics of head and neck squamous cell carcinomas, the cell kinetics and lectin binding patterns were compared with the histological classification and staging of the tumors, using surgically resected materials (maxillary sinus 10, oral cavity 21, pharynx 8, larynx 11). Eight biotinylated lectins (WGA, 1-PHA, ConA, UEA1, RCA1, SBA, DBA, PNA) were applied to the paraffin-embedded sections, and were visualized histochemically by the streptavidin-alkaline phosphatase method. The DNA contents of the isolated carcinoma cells obtained from the adjacent thick sections were evaluated using an epi-illumination cytofluorometer after propidium iodide staining. On lectin histochemistry, the binding pattern of WGA lectin was similar between carcinoma tissues and normal tissues, but the binding was more intense in well differentiated than less differentiated carcinomas. Lymph node metastasis was found to be related to the presence of cells with poor WGA-binding. In the binding patterns of the other lectins, RCA1, SBA and ConA were related to the differentiation of carcinomas, but they were not related to the TNM-classification. DNA cytofluorometry exhibited marked polyploidization, which progressed with the advancement of the clinical and pathological staging of carcinomas. However, the DNA ploidy pattern was not associated with the cell characteristics such as the degree of histological differentiation and the lectin-binding pattern, except that the appearance of aneuploidy had some relationship with the binding-patterns of UEA1 and 1-PHA.

Directional loudness in an anechoic sound field, head-related transfer functions, and binaural summation

DEFF Research Database (Denmark)

Sivonen, Ville Pekka; Ellermeier, Wolfgang

2006-01-01

planes. Matches were obtained via a two-interval, adaptive forced-choice (2AFC) procedure for three center frequencies (0.4, 1 and 5 kHz) and two overall levels (45 and 65 dB SPL). The results showed that loudness is not constant over sound incidence angles, with directional sensitivity varying over......The effect of sound incidence angle on loudness was investigated using real sound sources positioned in an anechoic chamber. Eight normal-hearing listeners produced loudness matches between a frontal reference location and seven sources placed at other directions, both in the horizontal and median...... a range of up to 10 dB, exhibiting considerable frequency dependence, but only minor effects of overall level. The pattern of results varied substantially between subjects, but was largely accounted for by variations in individual head-related transfer functions. Modeling of binaural loudness based...

Radiolabeled cetuximab: dose optimization for epidermal growth factor receptor imaging in a head-and-neck squamous cell carcinoma model

NARCIS (Netherlands)

Hoeben, B.A.W.; Molkenboer-Kuenen, J.D.M.; Oyen, W.J.G.; Peeters, W.J.M.; Kaanders, J.H.A.M.; Bussink, J.; Boerman, O.C.

2011-01-01

Noninvasive imaging of the epidermal growth factor receptor (EGFR) in head-and-neck squamous cell carcinoma could be of value to select patients for EGFR-targeted therapy. We assessed dose optimization of (111) Indium-DTPA-cetuximab ((111) In-cetuximab) for EGFR imaging in a head-and-neck squamous

Evolution of the new vertebrate head by co-option of an ancient chordate skeletal tissue.

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Jandzik, David; Garnett, Aaron T; Square, Tyler A; Cattell, Maria V; Yu, Jr-Kai; Medeiros, Daniel M

2015-02-26

A defining feature of vertebrates (craniates) is a pronounced head that is supported and protected by a robust cellular endoskeleton. In the first vertebrates, this skeleton probably consisted of collagenous cellular cartilage, which forms the embryonic skeleton of all vertebrates and the adult skeleton of modern jawless and cartilaginous fish. In the head, most cellular cartilage is derived from a migratory cell population called the neural crest, which arises from the edges of the central nervous system. Because collagenous cellular cartilage and neural crest cells have not been described in invertebrates, the appearance of cellular cartilage derived from neural crest cells is considered a turning point in vertebrate evolution. Here we show that a tissue with many of the defining features of vertebrate cellular cartilage transiently forms in the larvae of the invertebrate chordate Branchiostoma floridae (Florida amphioxus). We also present evidence that during evolution, a key regulator of vertebrate cartilage development, SoxE, gained new cis-regulatory sequences that subsequently directed its novel expression in neural crest cells. Together, these results suggest that the origin of the vertebrate head skeleton did not depend on the evolution of a new skeletal tissue, as is commonly thought, but on the spread of this tissue throughout the head. We further propose that the evolution of cis-regulatory elements near an ancient regulator of cartilage differentiation was a major factor in the evolution of the vertebrate head skeleton.

Tumor-Volume Simulation During Radiotherapy for Head-and-Neck Cancer Using a Four-Level Cell Population Model

International Nuclear Information System (INIS)

Chvetsov, Alexei V.; Dong Lei; Palta, Jantinder R.; Amdur, Robert J.

2009-01-01

Purpose: To develop a fast computational radiobiologic model for quantitative analysis of tumor volume during fractionated radiotherapy. The tumor-volume model can be useful for optimizing image-guidance protocols and four-dimensional treatment simulations in proton therapy that is highly sensitive to physiologic changes. Methods: The analysis is performed using two approximations: (1) tumor volume is a linear function of total cell number and (2) tumor-cell population is separated into four subpopulations: oxygenated viable cells, oxygenated lethally damaged cells, hypoxic viable cells, and hypoxic lethally damaged cells. An exponential decay model is used for disintegration and removal of oxygenated lethally damaged cells from the tumor. Results: We tested our model on daily volumetric imaging data available for 14 head-and-neck cancer patients treated with an integrated computed tomography/linear accelerator system. A simulation based on the averaged values of radiobiologic parameters was able to describe eight cases during the entire treatment and four cases partially (50% of treatment time) with a maximum 20% error. The largest discrepancies between the model and clinical data were obtained for small tumors, which may be explained by larger errors in the manual tumor volume delineation procedure. Conclusions: Our results indicate that the change in gross tumor volume for head-and-neck cancer can be adequately described by a relatively simple radiobiologic model. In future research, we propose to study the variation of model parameters by fitting to clinical data for a cohort of patients with head-and-neck cancer and other tumors. The potential impact of other processes, like concurrent chemotherapy, on tumor volume should be evaluated.

Definitive chemoradiotherapy with carboplatin for squamous cell carcinoma of the head and neck.

Science.gov (United States)

Nagasaka, Misako; Zaki, Mark; Issa, Majd; Kim, Harold; Abrams, Judith; Sukari, Ammar

2017-10-01

Definitive concurrent chemoradiotherapy (CRT) is considered the standard of care for organ preservation and is the only potentially curative therapy for surgically unresectable patients with stage III to IVb locally advanced squamous cell carcinoma of the head and neck. In patients with high risks for adverse events utilizing cisplatin, carboplatin has been empirically substituted. The objective of this study was to estimate the locoregional control rate, progression-free survival, overall survival, and adverse events in locally advanced squamous cell carcinoma of the head and neck patients treated with CRT utilizing carboplatin. A retrospective single-arm analysis. Data on consecutive patients who fit the eligibility criteria were collected. Eligible patients were treated with 70 Gy of radiation therapy and at least two cycles of carboplatin (area of curve [AUC] of 5 between January 2007 to December 2013. Fifty-four patients were identified. Overall locoregional control rate was 50% (95% confidence interval [CI] 37%-63%). Median progression-free and overall survival were 21 (CI 11-33) and 40 (CI 33-NA) months, respectively. One-, 3-, and 5-year overall survival were 81% (CI 67%-89%), 59% (CI 41%-73%), and 42% (CI 22%-61%), respectively. Stage III/IVa patients (n = 45) had a median survival of 62 (CI 37-NA months) and 3 years of 71% (CI 53%-84%), whereas stage IVb (n = 9) had a median survival of 31 (CI 4-NA) months and none survived to 3 years. Definitive CRT with carboplatin for locally advanced squamous cell carcinoma of the head and neck was well tolerated and demonstrated comparable results to CRT with cisplatin. 4. Laryngoscope, 127:2260-2264, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Trichostatin A, a histone deacetylase inhibitor, potentiated cytotoxic effect of lionizing radiation in human head and neck cancer cell lines

International Nuclear Information System (INIS)

Kim, Jin Ho; Shin, Jin Hee; Chie, Eui Kyu; Wu, Hong Gyun; Kim, Jae Sung; Kim, Il Han; Ha, Sung Whan; Park, Charn Il; Kang, Wee Saing

2004-01-01

We have previously reported that human glioblastoma cells are sensitized to radiation-induced death after their exposure to trichostatin A (TSA), a histone deacetylase inhibitor (HDAC-I), prior to the irradiation. We aimed to measure the magnitude of the radiosensitizing effect of TSA in human head and neck cancer cell lines. human head and neck cancer cell lines, HN-3 and HN-9, were exposed to 0, 50, 100, and 200 nM TSA for 18 hr prior to irradiation. Then, the TSA-treated cells were irradiated with 0, 2, 4, 6, and 8 Gy, and cell survival was measured by clonogenic assay. Pre-irradiation exposure to TSA was found to radiosensitize HN-3 and HN-9 cell lines. In HN-9 cells, the fraction surviving after 2 Gy (SF2) was significantly reduced by treatment of TSA at concentration as low as 50 nM. However, a treatment with 200 nM TSA was required to significantly decrease SF2 in the HN-3 cell line. SER of pre-irradiation treatment with 200 nM TSA was 1.84 in HN-3 and 7.24 in HN-9, respectively. Our results clearly showed that human head and neck cancer cell lines can be sensitized to ionizing radiation by pre-irradiation inhibition of histone deacetylase (HDAC) using TSA, and that this potentiation might well be a general phenomenon

Cathode-supported hybrid direct carbon fuel cells

DEFF Research Database (Denmark)

Gil, Vanesa; Gurauskis, Jonas; Deleebeeck, Lisa

2017-01-01

The direct conversion of coal to heat and electricity by a hybrid direct carbon fuel cell (HDCFC) is a highly efficient and cleaner technology than the conventional combustion power plants. HDCFC is defined as a combination of solid oxide fuel cell and molten carbonate fuel cell. This work...... investigates cathode-supported cells as an alternative configuration for HDCFC, with better catalytic activity and performance. This study aims to define the best processing route to manufacture highly efficient cathode-supported cells based on La0.75Sr0.25MnO3/yttria-stabilized zirconia infiltrated backbones...

Which features of advanced head and neck basal cell carcinoma are associated with perineural invasion?

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André Bandiera de Oliveira Santos

Full Text Available Abstract Introduction Perineural invasion is a unique route for tumor dissemination. In basal cell carcinomas, the incidence is low, but increases in advanced cases. Its importance is recognized but not fully understood. Objective To compare head and neck basal cell carcinomas with and without perineural invasion. Methods A retrospective medical chart review of multidisciplinary surgeries for basal cell carcinomas that required a head and neck surgery specialist in a tertiary referral center was performed. Clinical-demographics and histopathological features were analyzed. Results Of 354 cases, perineural invasion was present in 23.1%. Larger tumors and morpheaform subtype were statistically related to perineural invasion. Nodular and superficial subtypes were less frequent in positive cases. No significant difference was found in gender, age, ulceration, location, and mixed histology. Conclusion In this series of selected patients with basal cell carcinomas submitted to major resections, perineural invasion was clearly related to morpheaform subtype and to larger tumors. Other classically associated features, such as location in high-risk mask zone of the face, male gender and mixed histology, were not so strongly linked to perineural invasion.

Nanomedicines for inflammatory arthritis : head-to-head comparison of glucocorticoid-containing polymers, micelles, and liposomes

NARCIS (Netherlands)

Quan, Lingdong; Zhang, Yijia; Crielaard, Bart J; Dusad, Anand; Lele, Subodh M; Rijcken, Cristianne J F; Metselaar, Josbert M; Kostková, Hana; Etrych, Tomáš; Ulbrich, Karel; Kiessling, Fabian; Mikuls, Ted R; Hennink, Wim E; Storm, Gert; Lammers, Twan; Wang, Dong

2014-01-01

As an emerging research direction, nanomedicine has been increasingly utilized to treat inflammatory diseases. In this head-to-head comparison study, four established nanomedicine formulations of dexamethasone, including liposomes (L-Dex), core-cross-linked micelles (M-Dex), slow releasing polymeric

NEW OPPORTUNITIES FOR IMMUNE THERAPY IN PATIENTS WITH DISSEMINATED RECURRENT SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

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A. M. Mudunov

2017-01-01

Full Text Available Patients with head and neck squamous cell carcinoma diagnosed with recurrent tumor or distant metastases usually have the worst prognosis. Chemotherapeutic options are very limited in these patients; there is a probability of drug resistance development. The researchers continue to search more effective and less toxic drugs. In the current article, we analyze the results of the latest randomized clinical trials devoted the assessment of novel antitumor immunotherapeutic drugs – PD-1 inhibitors – in patients with head and neck squamous cell carcinoma. This studies reveal new possibilities for the treatment of these patients.

A computational study of low-head direct chill slab casting of aluminum alloy AA2024

Science.gov (United States)

Hasan, Mainul; Begum, Latifa

2016-04-01

The steady state casting of an industrial-sized AA2024 slab has been modeled for a vertical low-head direct chill caster. The previously verified 3-D CFD code is used to investigate the solidification phenomena of the said long-range alloy by varying the pouring temperature, casting speed and the metal-mold contact heat transfer coefficient from 654 to 702 °C, 60-180 mm/min, and 1.0-4.0 kW/(m2 K), respectively. The important predicted results are presented and thoroughly discussed.

Prognostic value of FDG PET/CT in head and neck squamous cell carcinomas

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Dequanter D

2015-08-01

Full Text Available D Dequanter,1,2 M Shahla,2 C Aubert,2 Y Deniz,2 P Lothaire2 1Department of Oncology, Laboratory of Experimental Radiotherapy, KU Leuven, Leuven, Belgium; 2Head and Neck Department, Hôpital André Vésale, CHU de Charleroi, Montigny le Tilleul, Belgium Introduction: The purpose of this study was to evaluate the use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT to identify the presence of cervical lymph nodes metastases and extracapsular spread with histologic correlations in head and neck squamous cell carcinoma.Methods: The medical records of 54 patients who underwent 18F-FDG PET/CT for head and neck squamous cell carcinoma before surgery were reviewed. Receiver operating characteristic (ROC analysis was performed to differentiate patients with cervical lymph node metastasis from those without lymph node metastasis. The same statistical analysis was done to differentiate cervical lymph nodes with extracapsular spread from those without extracapsular spread.Results: Metastatic disease was diagnosed histologically in 49% (26 of 54 of the patients. Extracapsular spread was present in ten of the 54 patients (19%. When ROC curve analysis and maximum standardized uptake (SUVmax values were used to detect cervical lymph node metastasis, the area under the ROC curve was 0.96 and the optimal cutoff value for SUVmax was 4.05 based on ROC curve analysis. The sensitivity and specificity of SUVmax for the detection of cervical lymph node metastasis using this cutoff point were 92% and 88%, respectively. When ROC curve analysis and SUVmax values were used in order to detect extracapsular spread, the area under the ROC curve was 0.86, and the optimal cutoff value for SUVmax was 4.15 based on ROC curve analysis. Using this cutoff value, the sensitivity and specificity of SUVmax for the detection of extracapsular spread were 83% and 88%, respectively.Conclusion: In our study, a median 18F-FDG PET/CT SUVmax cutoff

'Goats that stare at men': dwarf goats alter their behaviour in response to human head orientation, but do not spontaneously use head direction as a cue in a food-related context.

Science.gov (United States)

Nawroth, Christian; von Borell, Eberhard; Langbein, Jan

2015-01-01

Recently, comparative research on the mechanisms and species-specific adaptive values of attributing attentive states and using communicative cues has gained increased interest, particularly in non-human primates, birds, and dogs. Here, we investigate these phenomena in a farm animal species, the dwarf goat (Capra aegagrus hircus). In the first experiment, we investigated the effects of different human head and body orientations, as well as human experimenter presence/absence, on the behaviour of goats in a food-anticipating paradigm. Over a 30-s interval, the experimenter engaged in one of four different postures or behaviours (head and body towards the subject-'Control', head to the side, head and body away from the subject, or leaving the room) before delivering a reward. We found that the level of subjects' active anticipatory behaviour was highest in the control condition and decreased with a decreasing level of attention paid to the subject by the experimenter. Additionally, goats 'stared' (i.e. stood alert) at the experimental set-up for significantly more time when the experimenter was present but paid less attention to the subject ('Head' and 'Back' condition) than in the 'Control' and 'Out' conditions. In a second experiment, the experimenter provided different human-given cues that indicated the location of a hidden food reward in a two-way object choice task. Goats were able to use both 'Touch' and 'Point' cues to infer the correct location of the reward but did not perform above the level expected by chance in the 'Head only' condition. We conclude that goats are able to differentiate among different body postures of a human, including head orientation; however, despite their success at using multiple physical human cues, they fail to spontaneously use human head direction as a cue in a food-related context.

Conformational and functional analysis of the C-terminal globular head of the reovirus cell attachment protein.

Science.gov (United States)

Duncan, R; Horne, D; Strong, J E; Leone, G; Pon, R T; Yeung, M C; Lee, P W

1991-06-01

We have been investigating structure-function relationships in the reovirus cell attachment protein sigma 1 using various deletion mutants and protease analysis. In the present study, a series of deletion mutants were constructed which lacked 90, 44, 30, 12, or 4 amino acids from the C-terminus of the 455-amino acid-long reovirus type 3 (T3) sigma 1 protein. The full-length and truncated sigma 1 proteins were expressed in an in vitro transcription/translation system and assayed for L cell binding activity. It was found that the removal of as few as four amino acids from the C-terminus drastically affected the cell binding function of the sigma 1 protein. The C-terminal-truncated proteins were further characterized using trypsin, chymotrypsin, and monoclonal and polyclonal antibodies. Our results indicated that the C-terminal portions of the mutant proteins were misfolded, leading to a loss in cell binding function. The N-terminal fibrous tail of the proteins was unaffected by the deletions as was sigma 1 oligomerization, further illustrating the discrete structural and functional roles of the N- and C-terminal domains of sigma 1. In an attempt to identify smaller, functional peptides, full-length sigma 1 expressed in vitro was digested with trypsin and subsequently with chymotrypsin under various conditions. The results clearly demonstrated the highly stable nature of the C-terminal globular head of sigma 1, even when separated from the N-terminal fibrous tail. We concluded that: (1) the C-terminal globular head of sigma 1 exists as a compact, protease-resistant oligomeric structure; (2) an intact C-terminus is required for proper head folding and generation of the conformationally dependent cell binding domain.

Anticancer Effect and Apoptosis Induction of Cymbopogon citratus Plant on Head and Neck HTB43 Cancer Cell Lines

International Nuclear Information System (INIS)

Yen, N.; Zainah Adam; Arapoc, D.J.; Mohamed Zaffar Ali Mohamed Amiroudine; Shafii Khamis

2016-01-01

Lemongrass (Cymbopogon citratus) is a major crop in Asia, South and Central America, Africa and other tropical countries. It is commonly used as a culinary herb in Asian cuisine and also as medicinal herb in India. The objective of the present study was to investigate the anticancer effect of Cymbopogon citratus essential oil on human head and neck cancer cell lines. Lemongrass essential oil was obtained from fresh lemongrass leaves using the microwave extractor. The yield of the highly purified oil obtained was 0.62 %. The oil was investigated for its in-vitro cytotoxicity and apoptosis induction against human head and neck HTB43 cancer cell lines. The results showed promising cytotoxic effects with IC_5_0 value of 15.42 ± 6.10 μg/ ml (HTB43) respectively. In addition, the essential oil has found inducing apoptotic effect within HTB43 cells (25.71 ± 1.43 %). These preliminary results indicated that the oil had apoptosis-based cytotoxicity against head and neck cancer cells. However, further investigations need to be carried out in order to elucidate the anti-cancer properties of the oil. The phytochemicals properties of the active compounds found in the oil also need to be studied. (author)

The Role of HPV in Head and Neck Cancer Stem Cell Formation and Tumorigenesis

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Mark S. Swanson

2016-02-01

Full Text Available The cancer stem cell (CSC theory proposes that a minority of tumor cells are capable of self-replication and tumorigenesis. It is these minority of cells that are responsible for cancer metastasis and recurrence in head and neck squamous cell cancers (HNSCC. Human papilloma virus (HPV-related cancer of the oropharynx is becoming more prevalent, which makes understanding of the relationship between HPV and CSCs more important than ever. This relationship is critical because CSC behavior can be predicted based on cell surface markers, which makes them a suitable candidate for targeted therapy. New therapies are an exciting opportunity to advance past the stalled outcomes in HNSCC that have plagued patients and clinicians for several decades.

[Radiotherapy for head and neck squamous cell carcinoma: State of the art and future directions].

Science.gov (United States)

Schick, U; Huguet, F; Pointreau, Y; Pradier, O

2017-10-01

Therapeutic principles of radiation therapy in head and neck carcinomas will be discussed in this review. Intensity-modulated radiotherapy with concomitant cisplatin should be standard. In case of contraindication to chemotherapy, cetuximab is an option, while hyperfractionation should be considered in patients unfit for concomitant treatment. Concomitant chemotherapy should be administered in the presence of extracapsular extensions and positive margins in the postoperative setting. Current research areas such as desescalation in human papillomavirus-positive tumours, adaptive radiotherapy, radiomics and immunotherapy will also be addressed. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Matlab Source Code for Species Transport through Nafion Membranes in Direct Ethanol, Direct Methanol, and Direct Glucose Fuel Cells

OpenAIRE

JH, Summerfield; MW, Manley

2016-01-01

A simple simulation of chemical species movement is presented. The species traverse a Nafion membrane in a fuel cell. Three cells are examined: direct methanol, direct ethanol, and direct glucose. The species are tracked using excess proton concentration, electric field strength, and voltage. The Matlab computer code is provided.

Correlation of NF-κB signal pathway with tumor metastasis of human head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Yan, Ming; Xu, Qin; Zhang, Ping; Zhou, Xiao-jian; Zhang, Zhi-yuan; Chen, Wan-tao

2010-01-01

Nuclear factor-kappa B (NF-κB) signaling constitutes a key event in the multistep process of carcinogenesis, progression and treatment in many cancer types. However, the significance of NF-κB pathway for complex and tissue-specific aspects of head and neck cancer progression, such as invasion and metastasis, is less understood. The expression of NF-κB p65 in squamous cell carcinoma of the head and neck (SCCHN) clinical specimens by immunohistochemistry. The role of NF-κB activity in head and neck squamous cell carcinoma was determined by western blot, reporter assay and EMSA analysis in vitro and metastasis assays in vivo in different metastatic potential tumor cells. Furthermore, the apoptosis rate and expression of metastasis-related protein such as MMP9 and VEGF were examined by Annexin V/PI staining and Western blot, respectively. A higher level of active nuclear-localized NF-κB was observed in the metastatic SCCHN specimens group (p < 0.01). The NF-κB activities of SCCHN cell lines with different metastatic potentials were then determined and in excellent agreement with results found in SCCHN specimens, highly metastatic SCCHN cell lines expressed high level of NF-κB activity. The treatment of highly metastatic SCCHN cells with NF-κB inhibitors reduced the in vitro cell invasion capacity of the cells without affecting the apoptotic rate. Additionally, the NF-κB inhibitors significantly inhibited the experimental lung metastasis of Tb cells and lymph node metastasis of TL cells in nude mice. Furthermore, the expression of metastasis-related proteins, such as matrix metalloproteinase 9 and vascular endothelial growth factor, was inhibited by pyrrolidine dithiocarbonate. This study suggests that NF-κB activity significantly contributes to tumor hematologic and lymphatic metastases and may aid in the development of early detection methods or therapies targeting non-conventional molecular targets

Characterization of the head end cells at the West Valley Nuclear Fuel Reprocessing Plant

International Nuclear Information System (INIS)

Vance, R.F.

1986-11-01

The head-end cells at the West Valley Nuclear Fuel Reprocessing Plant are characterized in this report. These cells consist of the Process Mechanical Cell (PMC) where irradiated nuclear fuel was trimmed of excess hardware and sheared into short segments; and the General Purpose Cell (GPC) where the segments were collected and stored prior to dissolution, and leached hulls were packaged for disposal. Between 1966 and 1972, while Nuclear Fuels Services operated the plant, these cells became highly contaminated with radioactive materials. The purpose of this characterization work was to develop technical information as a basis of decontamination and decommissioning planning and engineering. It was accomplished by performing remote in-cell visual examinations, radiation surveys, and sampling. Supplementary information was obtained from available written records, out-of-cell inspections, and interviews with plant personnel

Gender differences in head-neck segment dynamic stabilization during head acceleration.

Science.gov (United States)

Tierney, Ryan T; Sitler, Michael R; Swanik, C Buz; Swanik, Kathleen A; Higgins, Michael; Torg, Joseph

2005-02-01

Recent epidemiological research has revealed that gender differences exist in concussion incidence but no study has investigated why females may be at greater risk of concussion. Our purpose was to determine whether gender differences existed in head-neck segment kinematic and neuromuscular control variables responses to an external force application with and without neck muscle preactivation. Forty (20 females and 20 males) physically active volunteers participated in the study. The independent variables were gender, force application (known vs unknown), and force direction (forced flexion vs forced extension). The dependent variables were kinematic and EMG variables, head-neck segment stiffness, and head-neck segment flexor and extensor isometric strength. Statistical analyses consisted of multiple multivariate and univariate analyses of variance, follow-up univariate analyses of variance, and t-tests (P Gender differences existed in head-neck segment dynamic stabilization during head angular acceleration. Females exhibited significantly greater head-neck segment peak angular acceleration (50%) and displacement (39%) than males despite initiating muscle activity significantly earlier (SCM only) and using a greater percentage of their maximum head-neck segment muscle activity (79% peak activity and 117% muscle activity area). The head-neck segment angular acceleration differences may be because females exhibited significantly less isometric strength (49%), neck girth (30%), and head mass (43%), resulting in lower levels of head-neck segment stiffness (29%). For our subject demographic, the results revealed gender differences in head-neck segment dynamic stabilization during head acceleration in response to an external force application. Females exhibited significantly greater head-neck segment peak angular acceleration and displacement than males despite initiating muscle activity earlier (SCM only) and using a greater percentage of their maximum head-neck segment

Novel Immunotherapeutic Approaches for Head and Neck Squamous Cell Carcinoma

Directory of Open Access Journals (Sweden)

Darrin V. Bann

2016-09-01

Full Text Available The immune system plays a key role in preventing tumor formation by recognizing and destroying malignant cells. For over a century, researchers have attempted to harness the immune response as a cancer treatment, although this approach has only recently achieved clinical success. Head and neck squamous cell carcinoma (HNSCC is the sixth most common cancer worldwide and is associated with cigarette smoking, alcohol consumption, betel nut use, and human papillomavirus infection. Unfortunately, worldwide mortality from HNSCC remains high, partially due to limits on therapy secondary to the significant morbidity associated with current treatments. Therefore, immunotherapeutic approaches to HNSCC treatment are attractive for their potential to reduce morbidity while improving survival. However, the application of immunotherapies to this disease has been challenging because HNSCC is profoundly immunosuppressive, resulting in decreased absolute lymphocyte counts, impaired natural killer cell function, reduced antigen-presenting cell function, and a tumor-permissive cytokine profile. Despite these challenges, numerous clinical trials testing the safety and efficacy of immunotherapeutic approaches to HNSCC treatment are currently underway, many of which have produced promising results. This review will summarize immunotherapeutic approaches to HNSCC that are currently undergoing clinical trials.

Customizable rigid head fixation for infants: technical note.

Science.gov (United States)

Udayakumaran, Suhas; Onyia, Chiazor U

2016-01-01

The need and advantages of rigid fixation of the head in cranial surgeries are well documented (Berryhill et al., Otolaryngol Head Neck Surg 121:269-273, 1999). Head fixation for neurosurgical procedures in infants and in early years has been a challenge and is fraught with risk. Despite the fact that pediatric pins are designed, rigid head fixation involving direct application of pins to the head of infants and slightly older children is still generally not safe (Agrawal and Steinbok, Childs Nerv Syst 22:1473-1474, 2006). Yet, there are some surgeries in which some form of rigid fixation is required (Agrawal and Steinbok, Childs Nerv Syst 22:1473-1474, 2006). We describe a simple technique to achieve rigid fixation of the head in infants for neurosurgical procedures. This involves applying a head band made of Plaster of Paris (POP) around the head and then applying the fixation pins of the fixation frame directly on to the POP. We have used this technique of head fixation successfully for infants with no complications.

Topographic Pattern Distribution of Head And Neck Squamous Cell ...

African Journals Online (AJOL)

FINEPRINT

value of 71% of SCC in Turkey. Nevertheless a similar report documented a relatively lower value especially in. Yemen where head and neck SCC constituted only 8% of all head and neck cancers. Reports from Yemen revealed that oral cavity SCC was the most common topographic site of all head and. 3 neck cancers.

Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Lacko, Martin [Department of Otorhinolaryngology—Head and Neck Surgery, Maastricht University Medical Center, Maastricht (Netherlands); Braakhuis, Boudewijn J.M. [Department of Otolaryngology—Head and Neck Surgery, VU University Medical Center, Amsterdam (Netherlands); Sturgis, Erich M. [Department of Head and Neck Surgery and Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Boedeker, Carsten C. [Department of Otorhinolaryngology—Head and Neck Surgery, Albert-Ludwigs-University, Freiburg, Germany and Department of Otorhinolaryngology - Head and Neck Surgery, HELIOS Hanseklinikum Stralsund, Stralsund (Germany); Suárez, Carlos [Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo (Spain); Instituto Universitario de Oncología del Principado de Asturias, Oviedo (Spain); Rinaldo, Alessandra; Ferlito, Alfio [ENT Clinic, University of Udine, Udine (Italy); Takes, Robert P., E-mail: robert.takes@radboudumc.nl [Department of Otolaryngology—Head and Neck Surgery, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands)

2014-05-01

Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and its incidence is growing. Although environmental carcinogens and carcinogenic viruses are the main etiologic factors, genetic predisposition obviously plays a risk-modulating role, given that not all individuals exposed to these carcinogens experience the disease. This review highlights some aspects of genetic susceptibility to HNSCC: among others, genetic polymorphisms in biotransformation enzymes, DNA repair pathway, apoptotic pathway, human papillomavirus-related pathways, mitochondrial polymorphisms, and polymorphism related to the bilirubin-metabolized pathway. Furthermore, epigenetic variations, familial forms of HNSCC, functional assays for HNSCC risk assessment, and the implications and perspectives of research on genetic susceptibility in HNSCC are discussed.

Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma

International Nuclear Information System (INIS)

Lacko, Martin; Braakhuis, Boudewijn J.M.; Sturgis, Erich M.; Boedeker, Carsten C.; Suárez, Carlos; Rinaldo, Alessandra; Ferlito, Alfio; Takes, Robert P.

2014-01-01

Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and its incidence is growing. Although environmental carcinogens and carcinogenic viruses are the main etiologic factors, genetic predisposition obviously plays a risk-modulating role, given that not all individuals exposed to these carcinogens experience the disease. This review highlights some aspects of genetic susceptibility to HNSCC: among others, genetic polymorphisms in biotransformation enzymes, DNA repair pathway, apoptotic pathway, human papillomavirus-related pathways, mitochondrial polymorphisms, and polymorphism related to the bilirubin-metabolized pathway. Furthermore, epigenetic variations, familial forms of HNSCC, functional assays for HNSCC risk assessment, and the implications and perspectives of research on genetic susceptibility in HNSCC are discussed

Influence of engineered surface on cell directionality and motility

International Nuclear Information System (INIS)

Tang, Qing Yuan; Pang, Stella W; Tong, Wing Yin; Shi, Peng; Lam, Yun Wah; Shi, Jue

2014-01-01

Control of cell migration is important in numerous key biological processes, and is implicated in pathological conditions such as cancer metastasis and inflammatory diseases. Many previous studies indicated that cell migration could be guided by micropatterns fabricated on cell culture surfaces. In this study, we designed a polydimethylsiloxane cell culture substrate with gratings punctuated by corners and ends, and studied its effects on the behavior of MC3T3-E1 osteoblast cells. MC3T3-E1 cells elongated and aligned with the gratings, and the migration paths of the cells appeared to be guided by the grating pattern. Interestingly, more than 88% of the cells cultured on these patterns were observed to reverse their migration directions at least once during the 16 h examination period. Most of the reversal events occurred at the corners and the ends of the pattern, suggesting these localized topographical features induce an abrupt loss in directional persistence. Moreover, the cell speed was observed to increase temporarily right after each directional reversal. Focal adhesion complexes were more well-established in cells on the angular gratings than on flat surfaces, but the formation of filipodia appeared to be imbalanced at the corners and the ends, possibly leading to the loss of directional persistence. This study describes the first engineered cell culture surface that consistently induces changes in the directional persistence of adherent cells. This will provide an experimental model for the study of this phenomenon and a valuable platform to control the cell motility and directionality, which can be used for cell screening and selection. (paper)

Head and neck squamous cell carcinoma: usefulness of diffusion-weighted MR imaging in the prediction of a neoadjuvant therapeutic effect

International Nuclear Information System (INIS)

Kato, Hiroki; Tanaka, Osamu; Hoshi, Hiroaki; Kanematsu, Masayuki; Mizuta, Keisuke; Aoki, Mitsuhiro; Shibata, Toshiyuki; Yamashita, Tomomi; Hirose, Yoshinobu

2009-01-01

The purpose of our study was to evaluate the usefulness of diffusion-weighted imaging in predicting the responses to neoadjuvant therapy for head and neck squamous cell carcinomas. Diffusion-weighted, T2-weighted, and gadolinium-enhanced T1-weighted images were obtained from 28 patients with untreated head and neck squamous cell carcinomas with histological proof. A blinded radiologist evaluated the quantitative and qualitative signal intensities and apparent diffusion coefficients (ADCs) in the lesions on each sequence. All patients were treated by neoadjuvant therapies, and the post-therapeutic tumor regression rate was determined. Both the quantitative and qualitative signal intensities on diffusion-weighted images showed positive correlations (r=0.367 and 0.412, p<.05), and the ADCs showed a weak, inversed correlation (r=-0.384, p<.05) with the tumor regression rates. Diffusion-weighted imaging including an assessment by ADCs may be able to predict tumor response to neoadjuvant therapy for head and neck squamous cell carcinomas. (orig.)

Identification and characterization of cancer stem cells in human head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Han, Jing; Fujisawa, Toshio; Husain, Syed R; Puri, Raj K

2014-01-01

Current evidence suggests that initiation, growth, and invasion of cancer are driven by a small population of cancer stem cells (CSC). Previous studies have identified CD44+ cells as cancer stem cells in head and neck squamous cell carcinoma (HNSCC). However, CD44 is widely expressed in most cells in HNSCC tumor samples and several cell lines tested. We previously identified a small population of CD24+/CD44+ cells in HNSCC. In this study, we examined whether this population of cells may represent CSC in HNSCC. CD24+/CD44+ cells from HNSCC cell lines were sorted by flow cytometry, and their phenotype was confirmed by qRT-PCR. Their self-renewal and differentiation properties, clonogenicity in collagen gels, and response to anticancer drugs were tested in vitro. The tumorigenicity potential of CD24+/CD44+ cells was tested in athymic nude mice in vivo. Our results show that CD24+/CD44+ cells possessed stemness characteristics of self-renewal and differentiation. CD24+/CD44+ cells showed higher cell invasion in vitro and made higher number of colonies in collagen gels compared to CD24-/CD44+ HNSCC cells. In addition, the CD24+/CD44+ cells were more chemo-resistant to gemcitabine and cisplatin compared to CD24-/CD44+ cells. In vivo, CD24+/CD44+ cells showed a tendency to generate larger tumors in nude mice compared to CD24-/CD44+ cell population. Our study clearly demonstrates that a distinct small population of CD24+/CD44+ cells is present in HNSCC that shows stem cell-like properties. This distinct small population of cells should be further characterized and may provide an opportunity to target HNSCC CSC for therapy

Inhibition of STAT-3 results in greater cetuximab sensitivity in head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Bonner, James A.; Yang, Eddy S.; Trummell, Hoa Q.; Nowsheen, Somaira; Willey, Christopher D.; Raisch, Kevin P.

2011-01-01

Objective: The inhibition of epidermal growth factor receptor (EGFr) with the monoclonal antibody cetuximab reduces cell proliferation and survival which correlates with increased DNA damage. Since the signal transducer and activator of transcription-3 (STAT-3) is involved in the EGFr-induced signaling pathway, we hypothesized that depletion of STAT-3 may augment cetuximab-induced processes in human head and neck cancer cells. Materials and methods: Human head and neck squamous carcinoma cells (UM-SCC-5) were transfected with short hairpin RNA (shRNA) against STAT-3 (STAT3-2.4 and 2.9 cells). A mutated form of this shRNA was transfected for a control (NEG4.17 cells). Radiosensitivity was assessed by a standard colony formation assay. Proliferation was assessed by daily cell counts following treatment and apoptosis was assessed by an annexin V-FITC assay. The alkaline comet assay was used to assess DNA damage. Results: The STAT-3 knockdown cells (STAT3-2.4 and STAT3-2.9 cells) demonstrated enhanced radiosensitivity compared to control NEG4.17 cells, which correlated with increased apoptosis. Also, the STAT-3 knockdown cells demonstrated decreased proliferation with cetuximab treatments compared to control cells (NEG4.17). The increased cetuximab sensitivity of the STAT-3 knockdown cells correlated with increased apoptosis and DNA damage compared to control cells (NEG4.17). Conclusion: These studies revealed that the greater anti-proliferative effects and increased cytotoxicity of cetuximab in the STAT3-2.4 and STAT3-2.9 cells compared to control NEG4.17 cells, may be a result of STAT3-mediated effects on cellular apoptosis and DNA damage.

A Quest for Initiating Cells of Head and Neck Cancer and Their Treatment

International Nuclear Information System (INIS)

Chen, Chao; Köberle, Beate; Kaufmann, Andreas M.; Albers, Andreas E.

2010-01-01

The biology of head and neck squamous cell carcinomas (HNSCC) and other cancers have been related to cancer stem-like cells (CSC). Specific markers, which vary considerably depending on tumor type or tissue of origin, characterize CSC. CSC are cancer initiating, sustaining and mostly quiescent. Compared to bulk tumors, CSC are less sensitive to chemo- and radiotherapy and may have low immunogenicity. Therapeutic targeting of CSC may improve clinical outcome. HNSCC has two main etiologies: human papillomavirus, a virus infecting epithelial stem cells, and tobacco and alcohol abuse. Here, current knowledge of HNSCC-CSC biology is reviewed and parallels to CSC of other origin are drawn where necessary for a comprehensive picture

Expression of Ku correlates with radiation sensitivities in the head and neck cancer cell lines

International Nuclear Information System (INIS)

Lee, Sang Wook; Yu, Eun Sil; Yi, So Lyoung; Son, Se Hee; Kim, Jong Hoon; Ahn, Seung Do; Shin, Seong Soo; Choi, Eun Kyung

2004-01-01

DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase consisting of a 470 kDa catalytic subunit (DNA-PKcs) and a heterodimeric regulatory complex, called Ku, which is composed of 70 kDa (Ku 70) and 86 kDa (Ku 80) proteins. The DNA-PK has been shown to play a pivotal role in rejoining DNA double-strand-breaks (dsb) in mammalian cells. The purpose of this study is to examine the relationship between the level of Ku expression and radiation sensitivity. Nine head and neck, cancer cell lines showed various intrinsic radiation sensitivities. Among the nine, AMC-HN-3 cell was the most sensitive for X-ray irradiation and AMC-HN-9 cell was the most resistance. The most sensitive and resistant cell lines were selected and the test sensitivity of radiation and expression of Ku were measured. Radiation sensitivity was obtained by colony forming assay and Ku protein expression using Western blot analysis. Ku80 increased expression by radiation, wheras Ku70 did not. Overexpression of Ku80 protein increased radiation resistance in AMC-HN9 cell line. There was a correlation between Ku80 expression and radiation resistance. Ku80 was shown to play an important role in radiation damage response. Induction of Ku80 expression had an important role in DNA damage repair by radiation. Ku80 expression may be an effective predictive assay of radiosensitivity on head and neck cancer

Chemoradiotherapy in head and neck squamous cell carcinoma: focus on targeted therapies

International Nuclear Information System (INIS)

Bozec, A.; Thariat, J.; Bensadoun, R.J.; Milano, G.

2008-01-01

Radiotherapy is an essential treatment for many patients with head and neck squamous cell carcinoma. Its association with molecular targeted therapies represents a real progress. Among the recent advances in the molecular targeted therapy of cancer, the applications centred on E.G.F.R. are currently the most promising and the most advanced at clinical level. Considering the set of therapeutic tools targeting E.G.F.R., there are at present two well-identified emerging categories of drugs with monoclonal antibodies, on the one hand, and tyrosine kinase inhibitors, on the other. In many preclinical studies, the combination of anti-E.G.F.R. drugs with irradiation has led to additive or supra-additive cytotoxic effects. Furthermore, anti-angiogenic agents have shown promising results in association with anti-E.G.F.R. drugs and radiotherapy. This research effort has recently produced encouraging clinical results in advanced head and neck cancer with combination of cetuximab (an anti-E.G.F.R. monoclonal antibody) with irradiation with a significant impact on patient survival. Active and efficient clinical research is currently ongoing to determine the place of molecular targeted therapies in the treatment of head and neck cancer, particularly in association with radiotherapy. (authors)

Data-Driven prioritisation of antibody-drug conjugate targets in head and neck squamous cell carcinoma

NARCIS (Netherlands)

Hanemaaijer, Saskia H; van Gijn, Stephanie E; Oosting, Sjoukje F; Plaat, Boudewijn E C; Moek, Kirsten L; Schuuring, Ed M; van der Laan, Bernard F A M; Roodenburg, Jan L N; van Vugt, Marcel A T M; van der Vegt, Bert; Fehrmann, Rudolf S N

BACKGROUND: For patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) palliative treatment options that improve overall survival are limited. The prognosis in this group remains poor and there is an unmet need for new therapeutic options. An emerging class of

Direct Differentiation of Human Pluripotent Stem Cells into Haploid Spermatogenic Cells

Directory of Open Access Journals (Sweden)

Charles A. Easley, IV

2012-09-01

Full Text Available Human embryonic stem cells (hESCs and induced pluripotent stem cells (hiPSCs have been shown to differentiate into primordial germ cells (PGCs but not into spermatogonia, haploid spermatocytes, or spermatids. Here, we show that hESCs and hiPSCs differentiate directly into advanced male germ cell lineages, including postmeiotic, spermatid-like cells, in vitro without genetic manipulation. Furthermore, our procedure mirrors spermatogenesis in vivo by differentiating PSCs into UTF1-, PLZF-, and CDH1-positive spermatogonia-like cells; HIWI- and HILI-positive spermatocyte-like cells; and haploid cells expressing acrosin, transition protein 1, and protamine 1 (proteins that are uniquely found in spermatids and/or sperm. These spermatids show uniparental genomic imprints similar to those of human sperm on two loci: H19 and IGF2. These results demonstrate that male PSCs have the ability to differentiate directly into advanced germ cell lineages and may represent a novel strategy for studying spermatogenesis in vitro.

The Aromatic Head Group of Spider Toxin Polyamines Influences Toxicity to Cancer Cells.

Science.gov (United States)

Wilson, David; Boyle, Glen M; McIntyre, Lachlan; Nolan, Matthew J; Parsons, Peter G; Smith, Jennifer J; Tribolet, Leon; Loukas, Alex; Liddell, Michael J; Rash, Lachlan D; Daly, Norelle L

2017-10-27

Spider venoms constitute incredibly diverse libraries of compounds, many of which are involved in prey capture and defence. Polyamines are often prevalent in the venom and target ionotropic glutamate receptors. Here we show that a novel spider polyamine, PA 366 , containing a hydroxyphenyl-based structure is present in the venom of several species of tarantula, and has selective toxicity against MCF-7 breast cancer cells. By contrast, a polyamine from an Australian funnel-web spider venom, which contains an identical polyamine tail to PA 366 but an indole-based head-group, is only cytotoxic at high concentrations. Our results suggest that the ring structure plays a role in the cytotoxicity and that modification to the polyamine head group might lead to more potent and selective compounds with potential as novel cancer treatments.

The Aromatic Head Group of Spider Toxin Polyamines Influences Toxicity to Cancer Cells

Directory of Open Access Journals (Sweden)

David Wilson

2017-10-01

Full Text Available Spider venoms constitute incredibly diverse libraries of compounds, many of which are involved in prey capture and defence. Polyamines are often prevalent in the venom and target ionotropic glutamate receptors. Here we show that a novel spider polyamine, PA366, containing a hydroxyphenyl-based structure is present in the venom of several species of tarantula, and has selective toxicity against MCF-7 breast cancer cells. By contrast, a polyamine from an Australian funnel-web spider venom, which contains an identical polyamine tail to PA366 but an indole-based head-group, is only cytotoxic at high concentrations. Our results suggest that the ring structure plays a role in the cytotoxicity and that modification to the polyamine head group might lead to more potent and selective compounds with potential as novel cancer treatments.

Human Papillomavirus Induced Transformation in Cervical and Head and Neck Cancers

Energy Technology Data Exchange (ETDEWEB)

Adams, Allie K. [Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229 (United States); Wise-Draper, Trisha M. [Division of Hematology/Oncology, University of Cincinnati Medical Center, University of Cincinnati, Cincinnati, OH 45229 (United States); Wells, Susanne I., E-mail: Susanne.Wells@cchmc.org [Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229 (United States)

2014-09-15

Human papillomavirus (HPV) is one of the most widely publicized and researched pathogenic DNA viruses. For decades, HPV research has focused on transforming viral activities in cervical cancer. During the past 15 years, however, HPV has also emerged as a major etiological agent in cancers of the head and neck, in particular squamous cell carcinoma. Even with significant strides achieved towards the screening and treatment of cervical cancer, and preventive vaccines, cervical cancer remains the leading cause of cancer-associated deaths for women in developing countries. Furthermore, routine screens are not available for those at risk of head and neck cancer. The current expectation is that HPV vaccination will prevent not only cervical, but also head and neck cancers. In order to determine if previous cervical cancer models for HPV infection and transformation are directly applicable to head and neck cancer, clinical and molecular disease aspects must be carefully compared. In this review, we briefly discuss the cervical and head and neck cancer literature to highlight clinical and genomic commonalities. Differences in prognosis, staging and treatment, as well as comparisons of mutational profiles, viral integration patterns, and alterations in gene expression will be addressed.

Human Papillomavirus Induced Transformation in Cervical and Head and Neck Cancers

International Nuclear Information System (INIS)

Adams, Allie K.; Wise-Draper, Trisha M.; Wells, Susanne I.

2014-01-01

Human papillomavirus (HPV) is one of the most widely publicized and researched pathogenic DNA viruses. For decades, HPV research has focused on transforming viral activities in cervical cancer. During the past 15 years, however, HPV has also emerged as a major etiological agent in cancers of the head and neck, in particular squamous cell carcinoma. Even with significant strides achieved towards the screening and treatment of cervical cancer, and preventive vaccines, cervical cancer remains the leading cause of cancer-associated deaths for women in developing countries. Furthermore, routine screens are not available for those at risk of head and neck cancer. The current expectation is that HPV vaccination will prevent not only cervical, but also head and neck cancers. In order to determine if previous cervical cancer models for HPV infection and transformation are directly applicable to head and neck cancer, clinical and molecular disease aspects must be carefully compared. In this review, we briefly discuss the cervical and head and neck cancer literature to highlight clinical and genomic commonalities. Differences in prognosis, staging and treatment, as well as comparisons of mutational profiles, viral integration patterns, and alterations in gene expression will be addressed

Photodynamic mechanisms induced by a combination of hypericin and a chlorin based-photosensitizer in head and neck squamous cell carcinoma cells.

OpenAIRE

Gyenge Emina Besic; Lüscher Daniel; Forny Patrick; Antoniol Martina; Geisberger Georg; Walt Heinrich; Patzke Greta; Maake Caroline

2013-01-01

The aim of this study was to elucidate photodynamic therapy (PDT) effects mediated by hypericin and a liposomal meso tetrahydroxyphenyl chlorin (mTHPC) derivative with focus on their 1:1 mixture on head and neck squamous cell carcinoma cell lines. Absorption excitation and photobleaching were monitored using fluorescence spectrometry showing the same spectral patterns for the mixture as measured for single photosensitizers. In the mixture mTHPC showed a prolonged photo stability. Singlet oxyg...

Connective tissue growth factor activates pluripotency genes and mesenchymal-epithelial transition in head and neck cancer cells.

Science.gov (United States)

Chang, Cheng-Chi; Hsu, Wen-Hao; Wang, Chen-Chien; Chou, Chun-Hung; Kuo, Mark Yen-Ping; Lin, Been-Ren; Chen, Szu-Ta; Tai, Shyh-Kuan; Kuo, Min-Liang; Yang, Muh-Hwa

2013-07-01

The epithelial-mesenchymal transition (EMT) is a key mechanism in both embryonic development and cancer metastasis. The EMT introduces stem-like properties to cancer cells. However, during somatic cell reprogramming, mesenchymal-epithelial transition (MET), the reverse process of EMT, is a crucial step toward pluripotency. Connective tissue growth factor (CTGF) is a multifunctional secreted protein that acts as either an oncoprotein or a tumor suppressor among different cancers. Here, we show that in head and neck squamous cell carcinoma (HNSCC), CTGF promotes the MET and reduces invasiveness. Moreover, we found that CTGF enhances the stem-like properties of HNSCC cells and increases the expression of multiple pluripotency genes. Mechanistic studies showed that CTGF induces c-Jun expression through αvβ3 integrin and that c-Jun directly activates the transcription of the pluripotency genes NANOG, SOX2, and POU5F1. Knockdown of CTGF in TW2.6 cells was shown to reduce tumor formation and attenuate E-cadherin expression in xenotransplanted tumors. In HNSCC patient samples, CTGF expression was positively correlated with the levels of CDH1, NANOG, SOX2, and POU5F1. Coexpression of CTGF and the pluripotency genes was found to be associated with a worse prognosis. These findings are valuable in elucidating the interplay between epithelial plasticity and stem-like properties during cancer progression and provide useful information for developing a novel classification system and therapeutic strategies for HNSCC. ©2013 AACR.

Identification of a Novel Proto-oncogenic Network in Head and Neck Squamous Cell Carcinoma.

Science.gov (United States)

Georgy, Smitha R; Cangkrama, Michael; Srivastava, Seema; Partridge, Darren; Auden, Alana; Dworkin, Sebastian; McLean, Catriona A; Jane, Stephen M; Darido, Charbel

2015-09-01

The developmental transcription factor Grainyhead-like 3 (GRHL3) plays a critical tumor suppressor role in the mammalian epidermis through direct regulation of PTEN and the PI3K/AKT/mTOR signaling pathway. GRHL3 is highly expressed in all tissues derived from the surface ectoderm, including the oral cavity, raising a question about its potential role in suppression of head and neck squamous cell carcinoma (HNSCC). We explored the tumor suppressor role of Grhl3 in HNSCC using a conditional knockout (Grhl3 (∆/-) /K14Cre (+) ) mouse line (n = 26) exposed to an oral chemical carcinogen. We defined the proto-oncogenic pathway activated in the HNSCC derived from these mice and assessed it in primary human HNSCC samples, normal oral epithelial cell lines carrying shRNA to GRHL3, and human HNSCC cell lines. Data were analyzed with two-sided chi square and Student's t tests. Deletion of Grhl3 in oral epithelium in mice did not perturb PTEN/PI3K/AKT/mTOR signaling, but instead evoked loss of GSK3B expression, resulting in stabilization and accumulation of c-MYC and aggressive HNSCC. This molecular signature was also evident in a subset of primary human HNSCC and HNSCC cell lines. Loss of Gsk3b in mice, independent of Grhl3, predisposed to chemical-induced HNSCC. Restoration of GSK3B expression blocked proliferation of normal oral epithelial cell lines carrying shRNA to GRHL3 (cell no., Day 8: Scramble ctl, 616±21.8 x 10(3) vs GRHL3-kd, 1194±44 X 10(3), P < .001; GRHL3-kd vs GRHL3-kd + GSK3B, 800±98.84 X 10(3), P = .003) and human HNSCC cells. We defined a novel molecular signature in mammalian HNSCC, suggesting new treatment strategies targeting the GRHL3/GSK3B/c-MYC proto-oncogenic network. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Non-smoking and non-drinking patients with head and neck squamous cell carcinoma: a distinct population.

NARCIS (Netherlands)

Farshadpour, F.; Hordijk, G.J.; Koole, R.A.; Slootweg, P.J.

2007-01-01

OBJECTIVE: To recognize specific clinicopathological characteristics of non-smoking and non-drinking (NSND) head and neck squamous cell carcinoma (HNSCC) patients. This can increase our knowledge regarding a potentially different carcinogenesis in these patients. STUDY DESIGN/METHODS: Retrospective

Effects of PPARα inhibition in head and neck paraganglioma cells.

Directory of Open Access Journals (Sweden)

Rosalba Florio

Full Text Available Head and neck paragangliomas (HNPGLs are rare tumors that may cause important morbidity, because of their tendency to infiltrate the skull base. At present, surgery is the only therapeutic option, but radical removal may be difficult or impossible. Thus, effective targets and molecules for HNPGL treatment need to be identified. However, the lack of cellular models for this rare tumor hampers this task. PPARα receptor activation was reported in several tumors and this receptor appears to be a promising therapeutic target in different malignancies. Considering that the role of PPARα in HNPGLs was never studied before, we analyzed the potential of modulating PPARα in a unique model of HNPGL cells. We observed an intense immunoreactivity for PPARα in HNPGL tumors, suggesting that this receptor has an important role in HNPGL. A pronounced nuclear expression of PPARα was also confirmed in HNPGL-derived cells. The specific PPARα agonist WY14643 had no effect on HNPGL cell viability, whereas the specific PPARα antagonist GW6471 reduced HNPGL cell viability and growth by inducing cell cycle arrest and caspase-dependent apoptosis. GW6471 treatment was associated with a marked decrease of CDK4, cyclin D3 and cyclin B1 protein expression, along with an increased expression of p21 in HNPGL cells. Moreover, GW6471 drastically impaired clonogenic activity of HNPGL cells, with a less marked effect on cell migration. Notably, the effects of GW6471 on HNPGL cells were associated with the inhibition of the PI3K/GSK3β/β-catenin signaling pathway. In conclusion, the PPARα antagonist GW6471 reduces HNPGL cell viability, interfering with cell cycle and inducing apoptosis. The mechanisms affecting HNPGL cell viability involve repression of the PI3K/GSK3β/β-catenin pathway. Therefore, PPARα could represent a novel therapeutic target for HNPGL.

Effect of bleomycin-radiotherapy combination in management of head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Shah, P.M.; Shukla, S.N.; Patel, K.M.; Patel, N.L.; Baboo, H.A.; Patel, D.D.

1981-01-01

Twenty-five patients with head and neck squamous cell carcinoma were treated with bleomycin-radiotherapy protocol, 15 mg bleomycin I.V. on alternate days followed by radiation within half an hour. The average total dose of bleomycin was 150 mg. Radiotherapy was given daily. Two patients were lost to follow-up very early in the course of the treatment and were removed from the study for statistical purposes. Thirty-six patients with head and neck squamous cell carcinoma who were treated with radiotherapy alone during the same period were used as controls. The patients were followed for two years. The incidence of response rate did not differ significantly between regimens; however, the incidence of side effects with bleomycin-radiotherapy, 82.61%, is significantly more than that of radiotherapy alone (52.78%). Median survial time (MST) of those responding to bleomycin-radiotherapy protocol was seven months and 12 days and for radiotherapy responders was six months. Neither the response rate nor the MST improve significantly after pretreatment with bleomycin. On the contrary, the incidence of side effects increased significantly

Cotransplantation of bone marrow mononuclear cells and umbilical cord mesenchymal stem cells in avascular necrosis of the femoral head.

Science.gov (United States)

Cai, J; Wu, Z; Huang, L; Chen, J; Wu, C; Wang, S; Deng, Z; Wu, W; Luo, F; Tan, J

2014-01-01

We sought to investigate the therapeutic effects of cotransplantation of autologous bone marrow mononuclear cells (BMMNCs) and allogeneic umbilical cord mesenchymal stem cells (UC-MSCs) on avascular necrosis of the femoral head (ANFH). In all, 30 patients (49 hips; 24 males and 6 females) with ANFH were enrolled. According to the system of the Association Research Circulation Osseous, there were 24 hips in phase II and 25 hips in phase Ⅲ. Blood supply to the femoral head was evaluated by using digital subtraction angiography. Generally, 60 to 80 mL of autologous BMMNCs and 30 to 50 mL of UC-MSCs were infused into the femoral head artery. Harris scores including pain and joint function were used to evaluate the effects before and 3, 6, 9, and 12 months after transplantation. Computed tomography and radiographs were performed before and 12 months after the treatment. Clinical symptoms of pain and claudication were gradually improved. After the treatment, 93.3% (28/30), 86.7% (26/30), and 86.7% (26/30) of patients showed relief of hip pain, improvement of joint function, and extended walking distances, respectively. The Harris scores were increased significantly at 3, 6, and 12 months posttransplant compared with those pretransplant. In addition, the bone lesions in 89.7% of hips (44/49) were improved as showed on computed tomography after transplantation. Cotransplantation of autologous BMMNCs and allogeneic UC-MSCs showed therapeutic effect on ANFH without severe adverse effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Quad shot - hypofractionated radiotherapy for palliation in advanced squamous cell carcinoma of head and neck

International Nuclear Information System (INIS)

Maqsood, T.; Ali, U.; Arif, S.

2017-01-01

The objective of this study was to determine the efficacy of quad-shot radiation therapy for palliation in locally advanced and metastatic inoperable squamous cell carcinomas of head and neck. Study Design: A quasi-experimental study. Place and Duration of Study: Oncology department, Combined Military Hospital Rawalpindi, from Sep 2012 to Sep 2013. Material and Methods: Thirty five patients were included with histologically confirmed advanced inoperable squamous cell carcinoma in head and neck region, performance status 2 or 3 and survival =3 months. Patients were treated with radiation therapy 14 Gy in four fractions, megavoltage beam, twice daily fractions (at least 6 hours apart), for 2 consecutive days. Symptoms due to cancer (pain and dysphagia) were assessed as per common toxicity criteria adverse event version 4.0 on day 0 before treatment and day 21 after start of treatment. Results: Grades of pain and dysphagia showed significant improvement after treatment with a p-value <0.001. A total of 91.4% patients showed an improvement in grade of pain (32 out of 35 patients) and 45.7% of patients showed improvement in grade of dysphagia (16 out of 35 patients). There was a statistically significant decrease in grades of pain and dysphagia after treatment. Conclusion: The short duration of hypofractionated radiotherapy with Quad Shot was effective with respect to symptom palliation in locally advanced and metastatic inoperable head and neck cancers.

Immunohistochemical biomarkers and FDG uptake on PET/CT in head and neck squamous cell carcinoma

DEFF Research Database (Denmark)

Rasmussen, Gregers Brünnich; Vogelius, Ivan R.; Rasmussen, Jacob H

2015-01-01

on the other. A number of previous studies have shown a relationship between glucose transport protein expression and 18F-Fludeoxyglucose (FDG) PET uptake. Here, FDG uptake is analyzed in relation to expression of a selected panel of IHC cancer biomarkers in head and neck squamous cell carcinomas (HNSCC...

Head and neck cancer: metronomic chemotherapy

International Nuclear Information System (INIS)

De Felice, Francesca; Musio, Daniela; Tombolini, Vincenzo

2015-01-01

In the era of personalized medicine, head and neck squamous cell carcinoma (HNSCC) represents a critical oncologic topic. Conventional chemotherapy regimens consist of drugs administration in cycles near or at the maximum tolerated dose (MDT), followed by a long drug-free period to permit the patient to recover from acute toxicities. Despite this strategy is successful in controlling the cancer process at the beginning, a significant number of HNSCC patients tend to recurred or progress, especially those patients with locally advanced or metastatic disease. The repertoire of drugs directed against tumor cells has greatly increased and metronomic chemotherapy (MC) could be an effective treatment option. It is the purpose of this article to review the concept of MC and describe its potential use in HNSCC. We provide an update of ongoing progress and current challenges related to this issue

Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer

Directory of Open Access Journals (Sweden)

Carolina Nör

2014-02-01

Full Text Available Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs. These unique cells, named here cancer stem cells (CSCs, proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6] for their survival and self-renewal in HNSCC. Here, we hypothesized that cisplatin enhances the stem cell fraction in HNSCC. To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B cells and observed that cisplatin treatment increased (P = .0013 the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDHhighCD44high]. Cisplatin promoted self-renewal and survival of CSCs in vitro, as seen by an increase in the number of orospheres in ultralow attachment plates and induction in B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1 and octamer-binding transcription factor 4 expression. Cisplatin-resistant cells expressed more Bmi-1 than cisplatinsensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDHhighCD44high immediately after surgery and plated onto ultralow attachment plates. IL-6-induced signal transducer and activator of transcription 3 (STAT3 phosphorylation (indicative of stemness was unaffected by treatment with cisplatin in UM-SCC-22B cells, whereas IL-6-induced extracellular signal-regulated kinase (ERK phosphorylation (indicative of differentiation processes was partially inhibited by cisplatin. Notably, cisplatin-induced Bmi-1 was inhibited by interleukin-6 receptor blockade in parental and cisplatin-resistant cells. Taken together, these results demonstrate that cisplatin enhances the fraction of CSCs

Tuning cell adhesion by direct nanostructuring silicon into cell repulsive/adhesive patterns

International Nuclear Information System (INIS)

Premnath, Priyatha; Tavangar, Amirhossein; Tan, Bo; Venkatakrishnan, Krishnan

2015-01-01

Developing platforms that allow tuning cell functionality through incorporating physical, chemical, or mechanical cues onto the material surfaces is one of the key challenges in research in the field of biomaterials. In this respect, various approaches have been proposed and numerous structures have been developed on a variety of materials. Most of these approaches, however, demand a multistep process or post-chemical treatment. Therefore, a simple approach would be desirable to develop bio-functionalized platforms for effectively modulating cell adhesion and consequently programming cell functionality without requiring any chemical or biological surface treatment. This study introduces a versatile yet simple laser approach to structure silicon (Si) chips into cytophobic/cytophilic patterns in order to modulate cell adhesion and proliferation. These patterns are fabricated on platforms through direct laser processing of Si substrates, which renders a desired computer-generated configuration into patterns. We investigate the morphology, chemistry, and wettability of the platform surfaces. Subsequently, we study the functionality of the fabricated platforms on modulating cervical cancer cells (HeLa) behaviour. The results from in vitro studies suggest that the nanostructures efficiently repel HeLa cells and drive them to migrate onto untreated sites. The study of the morphology of the cells reveals that cells evade the cytophobic area by bending and changing direction. Additionally, cell patterning, cell directionality, cell channelling, and cell trapping are achieved by developing different platforms with specific patterns. The flexibility and controllability of this approach to effectively structure Si substrates to cell-repulsive and cell-adhesive patterns offer perceptible outlook for developing bio-functionalized platforms for a variety of biomedical devices. Moreover, this approach could pave the way for developing anti-cancer platforms that selectively repel

Tuning cell adhesion by direct nanostructuring silicon into cell repulsive/adhesive patterns

Energy Technology Data Exchange (ETDEWEB)

Premnath, Priyatha, E-mail: priyatha.premnath@ryerson.ca [Micro/Nanofabrication Laboratory, Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3 (Canada); Tavangar, Amirhossein, E-mail: atavanga@ryerson.ca [Micro/Nanofabrication Laboratory, Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3 (Canada); Tan, Bo, E-mail: tanbo@ryerson.ca [Nanocharacterization Laboratory, Department of Aerospace Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3 (Canada); Venkatakrishnan, Krishnan, E-mail: venkat@ryerson.ca [Micro/Nanofabrication Laboratory, Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3 (Canada)

2015-09-10

Developing platforms that allow tuning cell functionality through incorporating physical, chemical, or mechanical cues onto the material surfaces is one of the key challenges in research in the field of biomaterials. In this respect, various approaches have been proposed and numerous structures have been developed on a variety of materials. Most of these approaches, however, demand a multistep process or post-chemical treatment. Therefore, a simple approach would be desirable to develop bio-functionalized platforms for effectively modulating cell adhesion and consequently programming cell functionality without requiring any chemical or biological surface treatment. This study introduces a versatile yet simple laser approach to structure silicon (Si) chips into cytophobic/cytophilic patterns in order to modulate cell adhesion and proliferation. These patterns are fabricated on platforms through direct laser processing of Si substrates, which renders a desired computer-generated configuration into patterns. We investigate the morphology, chemistry, and wettability of the platform surfaces. Subsequently, we study the functionality of the fabricated platforms on modulating cervical cancer cells (HeLa) behaviour. The results from in vitro studies suggest that the nanostructures efficiently repel HeLa cells and drive them to migrate onto untreated sites. The study of the morphology of the cells reveals that cells evade the cytophobic area by bending and changing direction. Additionally, cell patterning, cell directionality, cell channelling, and cell trapping are achieved by developing different platforms with specific patterns. The flexibility and controllability of this approach to effectively structure Si substrates to cell-repulsive and cell-adhesive patterns offer perceptible outlook for developing bio-functionalized platforms for a variety of biomedical devices. Moreover, this approach could pave the way for developing anti-cancer platforms that selectively repel

Head Start Instructional Professionals' Inclusion Perceptions and Practices

Science.gov (United States)

Muccio, Leah S.; Kidd, Julie K.; White, C. Stephen; Burns, M. Susan

2014-01-01

This study considered the facilitators and barriers of successful inclusion in Head Start classrooms by examining the perspectives and practices of instructional professionals. A cross-sectional survey design was combined with direct observation in inclusive Head Start classrooms. Survey data were collected from 71 Head Start instructional…

Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton.

Directory of Open Access Journals (Sweden)

Cheng Cui

2013-11-01

Full Text Available Planar cell polarity (PCP regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin

E-cadherin expression and prognosis of head and neck squamous cell carcinoma: evidence from 19 published investigations

Directory of Open Access Journals (Sweden)

Ren X

2016-04-01

Full Text Available Xusheng Ren,1,2 Jianning Wang,2 Xuefen Lin,1,3 Xuxia Wang1,3 1Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Shandong University, 2Department of Oral and Maxillofacial Surgery, Jinan Stomatological Hospital, 3Shandong Province Key Laboratory of Oral Tissue Regeneration, Stomatological Hospital of Shandong University, Jinan, Shandong Province, People’s Republic of China Objective: The objective of this study was to review the published literature and investigate whether E-cadherin gene is a prognostic factor in head and neck squamous cell carcinoma by conducting a meta-analysis.Methods: Studies were identified from the databases Embase, Medline, and Cochrane Library by using the keywords “E-cadherin gene” and “head and neck cancer”. Overall survival (OS and disease-free survival (DFS were the primary outcome measurements.Results: Our literature review identified 1,458 articles; 19 studies with a total number of 2,012 cases were eligible for inclusion in the meta-analysis. The hazard ratio (HR for OS of patients with decreased expression of E-cadherin gene was 0.57 (95% CI =0.37, 0.89; P=0.000. However, statistical heterogeneity was unacceptably high (I2=74.5%, P=0.000. After sensitivity analysis, heterogeneity became acceptable, and the effect measure was still significant (I2=7.0%; HR =0.52; 95% CI =0.40, 0.66; P=0.000. The HR for DFS was 0.53 (95% CI =0.42, 0.67; P=0.000.Conclusion: This meta-analysis showed clear evidence that high E-cadherin gene expression is a positive prognostic factor of head and neck squamous cell carcinoma, resulting in better OS and DFS. However, this conclusion must be interpreted with caution due to a few limitations. Keywords: E-cadherin gene, prognosis, head and neck squamous cell carcinoma, immunohistochemistry 

Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

DEFF Research Database (Denmark)

Xiao, Fei; Fofana, Isabel; Heydmann, Laura

2014-01-01

Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies....... In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV...... genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host...

Automatic picking of direct P, S seismic phases and fault zone head waves

Science.gov (United States)

Ross, Z. E.; Ben-Zion, Y.

2014-10-01

We develop a set of algorithms for automatic detection and picking of direct P and S waves, as well as fault zone head waves (FZHW), generated by earthquakes on faults that separate different lithologies and recorded by local seismic networks. The S-wave picks are performed using polarization analysis and related filters to remove P-wave energy from the seismograms, and utilize STA/LTA and kurtosis detectors in tandem to lock on the phase arrival. The early portions of P waveforms are processed with STA/LTA, kurtosis and skewness detectors for possible first-arriving FZHW. Identification and picking of direct P and FZHW is performed by a multistage algorithm that accounts for basic characteristics (motion polarities, time difference, sharpness and amplitudes) of the two phases. The algorithm is shown to perform well on synthetic seismograms produced by a model with a velocity contrast across the fault, and observed data generated by earthquakes along the Parkfield section of the San Andreas fault and the Hayward fault. The developed techniques can be used for systematic processing of large seismic waveform data sets recorded near major faults.

Multicenter validation of recursive partitioning analysis classification for patients with squamous cell head and neck carcinoma treated with surgery and postoperative radiotherapy.

NARCIS (Netherlands)

Jonkman, A.; Kaanders, J.H.A.M.; Terhaard, C.H.J.; Hoebers, F.J.; Ende, P.L. van den; Wijers, O.B.; Verhoef, C.G.; Jong, M. de; Leemans, C.R.; Langendijk, J.A.

2007-01-01

PURPOSE: To validate the recursive partitioning analysis (RPA) classification system for squamous cell head and neck cancer as recently reported by the VU University Medical Center. METHODS AND MATERIALS: In eight Dutch head and neck cancer centers, data necessary to classify patients according to

Effect of ionizing radiation on the physical biology of head and neck squamous cell carcinoma cells.

Science.gov (United States)

Baker-Groberg, Sandra M; Bornstein, Sophia; Zilberman-Rudenko, Jevgenia; Schmidt, Mark; Tormoen, Garth W; Kernan, Casey; Thomas, Charles R; Wong, Melissa H; Phillips, Kevin G; McCarty, Owen J T

2015-09-01

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide. Although there are numerous treatment options for HNSCC, such as surgery, cytotoxic chemotherapy, molecularly targeted systemic therapeutics, and radiotherapy, overall survival has not significantly improved in the last 50 years. This suggests a need for a better understanding of how these cancer cells respond to current treatments in order to improve treatment paradigms. Ionizing radiation (IR) promotes cancer cell death through the creation of cytotoxic DNA lesions, including single strand breaks, base damage, crosslinks, and double strand breaks (DSBs). As unrepaired DSBs are the most cytotoxic DNA lesion, defining the downstream cellular responses to DSBs are critical for understanding the mechanisms of tumor cell responses to IR. The effects of experimental IR on HNSCC cells beyond DNA damage in vitro are ill-defined. Here we combined label-free, quantitative phase and fluorescent microscopy to define the effects of IR on the dry mass and volume of the HNSCC cell line, UM-SCC-22A. We quantified nuclear and cytoplasmic subcellular density alterations resulting from 8 Gy X-ray IR and correlated these signatures with DNA and γ-H2AX expression patterns. This study utilizes a synergistic imaging approach to study both biophysical and biochemical alterations in cells following radiation damage and will aid in future understanding of cellular responses to radiation therapy.

Direct fuel cell product design improvement

Energy Technology Data Exchange (ETDEWEB)

Maru, H.C.; Farooque, M. [Energy Research Corp., Danbury, CT (United States)

1996-12-31

Significant milestones have been attained towards the technology development field testing and commercialization of direct fuel cell power plant since the 1994 Fuel Cell Seminar. Under a 5-year cooperative agreement with the Department of Energy signed in December 1994, Energy Research Corporation (ERC) has been developing the design for a MW-scale direct fuel cell power plant with input from previous technology efforts and the Santa Clara Demonstration Project. The effort encompasses product definition in consultation with the Fuel Cell Commercialization Group, potential customers, as well as extensive system design and packaging. Manufacturing process improvements, test facility construction, cell component scale up, performance and endurance improvements, stack engineering, and critical balance-of-plant development are also addressed. Major emphasis of this product design improvement project is on increased efficiency, compactness and cost reduction to establish a competitive place in the market. A 2.85 MW power plant with an efficiency of 58% and a footprint of 420 m{sup 2} has been designed. Component and subsystem testing is being conducted at various levels. Planning and preparation for verification of a full size prototype unit are in progress. This paper presents the results obtained since the last fuel cell seminar.

High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck

Directory of Open Access Journals (Sweden)

Michael J. Veness

2007-01-01

Full Text Available Nonmelanoma skin cancers (squamous cell and basal cell carcinomas occur at an epidemic rate in many countries with the worldwide incidence increasing. The sun-exposed head and neck are the most frequent sites for these cancers to arise and in most patients diagnosed with a cutaneous squamous cell carcinoma, local treatment is usually curative. However, a subset is diagnosed with a high-risk cutaneous squamous cell carcinoma. High-risk factors include size (> 2 cm, thickness/depth of invasion (> 4 mm, recurrent lesions, the presence of perineural invasion, location near the parotid gland, and immunosuppression. These patients have a higher risk (> 10–20% of developing metastases to regional lymph nodes (often parotid nodes, and in some cases also of experiencing local morbidity (perineural invasion, based on unfavourable primary lesion and patient factors. Despite treatment, many patients developing metastatic cutaneous squamous cell carcinoma experience mortality and morbidity usually as a consequence of uncontrolled metastatic nodal disease. It is therefore important that clinicians treating nonmelanoma skin cancers have an understanding and awareness of these high-risk patients. The aim of this article is to discuss the factors that define a high-risk patient and to present some of the issues pertinent to their management.

Lightweight Stacks of Direct Methanol Fuel Cells

Science.gov (United States)

Narayanan, Sekharipuram; Valdez, Thomas

2004-01-01

An improved design concept for direct methanol fuel cells makes it possible to construct fuel-cell stacks that can weigh as little as one-third as much as do conventional bipolar fuel-cell stacks of equal power. The structural-support components of the improved cells and stacks can be made of relatively inexpensive plastics. Moreover, in comparison with conventional bipolar fuel-cell stacks, the improved fuel-cell stacks can be assembled, disassembled, and diagnosed for malfunctions more easily. These improvements are expected to bring portable direct methanol fuel cells and stacks closer to commercialization. In a conventional bipolar fuel-cell stack, the cells are interspersed with bipolar plates (also called biplates), which are structural components that serve to interconnect the cells and distribute the reactants (methanol and air). The cells and biplates are sandwiched between metal end plates. Usually, the stack is held together under pressure by tie rods that clamp the end plates. The bipolar stack configuration offers the advantage of very low internal electrical resistance. However, when the power output of a stack is only a few watts, the very low internal resistance of a bipolar stack is not absolutely necessary for keeping the internal power loss acceptably low.

Follow-up strategies in head and neck cancer other than upper aerodigestive tract squamous cell carcinoma

NARCIS (Netherlands)

Digonnet, Antoine; Hamoir, Marc; Andry, Guy; Vander Poorten, Vincent; Haigentz, Missak; Langendijk, Johannes A.; de Bree, Remco; Hinni, Michael L.; Mendenhall, William M.; Paleri, Vinidh; Rinaldo, Alessandra; Werner, Jochen A.; Takes, Robert P.; Ferlito, Alfio

Post-therapy follow-up for patients with head and neck cancer other than upper aerodigestive tract squamous cell carcinoma should meet several objectives: to detect both local, regional or distant recurrences, to evaluate acute and long-term treatment-related side effects, to guide the

Direct sorbitol proton exchange membrane fuel cell using moderate catalyst loadings

International Nuclear Information System (INIS)

Oyarce, Alejandro; Gonzalez, Carlos; Lima, Raquel Bohn; Lindström, Rakel Wreland; Lagergren, Carina; Lindbergh, Göran

2014-01-01

Highlights: •The performance of a direct sorbitol fuel cell was evaluated at different temperatures. •The performance was compared to the performance of a direct glucose fuel cell. •The mass specific peak power density of the direct sorbitol fuel cell was 3.6 mW mg −1 totalcatalystloading at 80 °C. •Both sorbitol and glucose fuel cell suffer from deactivation. -- Abstract: Recent progress in biomass hydrolysis has made it interesting to study the use of sorbitol for electricity generation. In this study, sorbitol and glucose are used as fuels in proton exchange membrane fuel cells having 0.9 mg cm −2 PtRu/C at the anode and 0.3 mg cm −2 Pt/C at the cathode. The sorbitol oxidation was found to have slower kinetics than glucose oxidation. However, at low temperatures the direct sorbitol fuel cell shows higher performance than the direct glucose fuel cell, attributed to a lower degree of catalyst poisoning. The performance of both fuel cells is considerably improved at higher temperatures. High temperatures lower the poisoning, allowing the direct glucose fuel cell to reach a higher performance than the direct sorbitol fuel cell. The mass specific peak power densities of the direct sorbitol and direct glucose fuel cells at 65 °C was 3.2 mW mg −1 catalyst and 3.5 mW mg −1 catalyst , respectively. Both of these values are one order of magnitude larger than mass specific peak power densities of earlier reported direct glucose fuel cells using proton exchange membranes. Furthermore, both the fuel cells showed a considerably decrease in performance with time, which is partially attributed to sorbitol and glucose crossover poisoning the Pt/C cathode

Profile of pembrolizumab in the treatment of head and neck squamous cell carcinoma: design development and place in therapy

Directory of Open Access Journals (Sweden)

Haque S

2017-08-01

Full Text Available Sulsal Haque,1,2 Mahender Yellu,1,2 Jaskirat Randhawa,1,2 Nooshin Hashemi-Sadraei1,2 1Division of Hematology/Oncology, Department of Medicine, University of Cincinnati, 2University of Cincinnati Cancer Institute, Cincinnati, OH, USA Abstract: Head and neck squamous cell cancer (HNSCC is the sixth most common malignancy worldwide, and despite advances in cytotoxic, surgical and radiation techniques, outcomes are still poor in those with both locally advanced and metastatic diseases. The need for development of better therapeutics along with a greater understanding of the relationship between the immune system and malignancies has led to a new therapeutic modality, immune modulators, particularly checkpoint inhibitors in HNSCC. It is now well recognized that HNSCC circumvents crucial pathways utilized by the immune system to escape surveillance. These hijacked pathways include impairing tumor antigen presentation machinery and co-opting checkpoint receptors. This understanding has led to the development of monoclonal antibodies targeting checkpoint receptors and has resulted in promising outcomes in HNSCC. This article describes the mechanisms that HNSCC utilizes to escape immune surveillance, clinical impact of checkpoint inhibitors (with a focus on pembrolizumab, ongoing studies, and future directions. Keywords: pembrolizumab, head and neck cancer, MK-3475, immunotherapy

Advances in direct oxidation methanol fuel cells

Science.gov (United States)

Surampudi, S.; Narayanan, S. R.; Vamos, E.; Frank, H.; Halpert, G.; Laconti, Anthony B.; Kosek, J.; Prakash, G. K. Surya; Olah, G. A.

1993-01-01

Fuel cells that can operate directly on fuels such as methanol are attractive for low to medium power applications in view of their low weight and volume relative to other power sources. A liquid feed direct methanol fuel cell has been developed based on a proton exchange membrane electrolyte and Pt/Ru and Pt catalyzed fuel and air/O2 electrodes, respectively. The cell has been shown to deliver significant power outputs at temperatures of 60 to 90 C. The cell voltage is near 0.5 V at 300 mA/cm(exp 2) current density and an operating temperature of 90 C. A deterrent to performance appears to be methanol crossover through the membrane to the oxygen electrode. Further improvements in performance appear possible by minimizing the methanol crossover rate.

Alpha-2 Heremans Schmid Glycoprotein (AHSG) Modulates Signaling Pathways in Head and Neck Squamous Cell Carcinoma Cell Line SQ20B

Energy Technology Data Exchange (ETDEWEB)

Thompson, Pamela D.; Sakwe, Amos [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Koumangoye, Rainelli [Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Yarbrough, Wendell G. [Division of Otolaryngology, Departments of Surgery and Pathology and Yale Cancer Center, Yale University, New Haven, CT 06520 (United States); Ochieng, Josiah [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Marshall, Dana R., E-mail: dmarshall@mmc.edu [Department of Pathology, Anatomy and Cell Biology, Meharry Medical College, Nashville, TN 37208 (United States)

2014-02-15

This study was performed to identify the potential role of Alpha-2 Heremans Schmid Glycoprotein (AHSG) in Head and Neck Squamous Cell Carcinoma (HNSCC) tumorigenesis using an HNSCC cell line model. HNSCC cell lines are unique among cancer cell lines, in that they produce endogenous AHSG and do not rely, solely, on AHSG derived from serum. To produce our model, we performed a stable transfection to down-regulate AHSG in the HNSCC cell line SQ20B, resulting in three SQ20B sublines, AH50 with 50% AHSG production, AH20 with 20% AHSG production and EV which is the empty vector control expressing wild-type levels of AHSG. Utilizing these sublines, we examined the effect of AHSG depletion on cellular adhesion, proliferation, migration and invasion in a serum-free environment. We demonstrated that sublines EV and AH50 adhered to plastic and laminin significantly faster than the AH20 cell line, supporting the previously reported role of exogenous AHSG in cell adhesion. As for proliferative potential, EV had the greatest amount of proliferation with AH50 proliferation significantly diminished. AH20 cells did not proliferate at all. Depletion of AHSG also diminished cellular migration and invasion. TGF-β was examined to determine whether levels of the TGF-β binding AHSG influenced the effect of TGF-β on cell signaling and proliferation. Whereas higher levels of AHSG blunted TGF-β influenced SMAD and ERK signaling, it did not clearly affect proliferation, suggesting that AHSG influences on adhesion, proliferation, invasion and migration are primarily due to its role in adhesion and cell spreading. The previously reported role of AHSG in potentiating metastasis via protecting MMP-9 from autolysis was also supported in this cell line based model system of endogenous AHSG production in HNSCC. Together, these data show that endogenously produced AHSG in an HNSCC cell line, promotes in vitro cellular properties identified as having a role in tumorigenesis. Highlights: • Head

Alpha-2 Heremans Schmid Glycoprotein (AHSG) Modulates Signaling Pathways in Head and Neck Squamous Cell Carcinoma Cell Line SQ20B

International Nuclear Information System (INIS)

Thompson, Pamela D.; Sakwe, Amos; Koumangoye, Rainelli; Yarbrough, Wendell G.; Ochieng, Josiah; Marshall, Dana R.

2014-01-01

This study was performed to identify the potential role of Alpha-2 Heremans Schmid Glycoprotein (AHSG) in Head and Neck Squamous Cell Carcinoma (HNSCC) tumorigenesis using an HNSCC cell line model. HNSCC cell lines are unique among cancer cell lines, in that they produce endogenous AHSG and do not rely, solely, on AHSG derived from serum. To produce our model, we performed a stable transfection to down-regulate AHSG in the HNSCC cell line SQ20B, resulting in three SQ20B sublines, AH50 with 50% AHSG production, AH20 with 20% AHSG production and EV which is the empty vector control expressing wild-type levels of AHSG. Utilizing these sublines, we examined the effect of AHSG depletion on cellular adhesion, proliferation, migration and invasion in a serum-free environment. We demonstrated that sublines EV and AH50 adhered to plastic and laminin significantly faster than the AH20 cell line, supporting the previously reported role of exogenous AHSG in cell adhesion. As for proliferative potential, EV had the greatest amount of proliferation with AH50 proliferation significantly diminished. AH20 cells did not proliferate at all. Depletion of AHSG also diminished cellular migration and invasion. TGF-β was examined to determine whether levels of the TGF-β binding AHSG influenced the effect of TGF-β on cell signaling and proliferation. Whereas higher levels of AHSG blunted TGF-β influenced SMAD and ERK signaling, it did not clearly affect proliferation, suggesting that AHSG influences on adhesion, proliferation, invasion and migration are primarily due to its role in adhesion and cell spreading. The previously reported role of AHSG in potentiating metastasis via protecting MMP-9 from autolysis was also supported in this cell line based model system of endogenous AHSG production in HNSCC. Together, these data show that endogenously produced AHSG in an HNSCC cell line, promotes in vitro cellular properties identified as having a role in tumorigenesis. Highlights: • Head

Stem Cell Therapy for Avascular Necrosis of Femoral Head in Sickle Cell Disease: Report of 11 Cases and Review of Literature.

Science.gov (United States)

Sadat-Ali, Mir; Azam, Md Q; Elshabouri, Ezzat M; Tantawy, Ahmad M; Acharya, Sadananda

2017-11-30

Sickle cell disease (SCD) is quite common in eastern Saudi Arabia and Avascular necrosis of femoral head (ANFH) occurs in 30% of the young patients leading to early joint arthroplasty. This study was conducted to assess the benefits of injection of osteoblasts in the avascular lesions of the head of femur. A preset technique was used, 10 CC of bone marrow aspiration was performed under local anesthesia and aseptic technique. Osteoblasts were separated from the bone marrow cells. The avascular area was drilled and 10 million osteoblasts were transplanted at the lesion site. Patients were seen in the out patient clinic after two weeks for removal of the suture and addressed the questionnaire and examined for the range of movement. The follow up MRI was performed at 4 months. The average age was 20.2±3.9 years. The mean hemoglobin S was 81.6±4.8 percent. Quality of Life Score for Chronic Hip Disease was assessed and found at 8.6 (1 being the severe limitation and 10 being normal), whereas Harris hip score improved from 41.7±5.1 to 88.93±3.6 (p avascular lesions. The short term results were good and we believe the injection of osteoblast in the avascular lesion of head of femur is a less invasive procedure devoid of any untoward complications and merits such treatment in large patient group with longer follow up.

Head Start Impact Study

Data.gov (United States)

U.S. Department of Health & Human Services — Nationally representative, longitudinal information from an evaluation where children were randomly assigned to Head Start or community services as usual;direct...

Modular reactor head shielding system

International Nuclear Information System (INIS)

Jacobson, E. B.

1985-01-01

An improved modular reactor head shielding system is provided that includes a frame which is removably assembled on a reactor head such that no structural or mechanical alteration of the head is required. The shielding system also includes hanging assemblies to mount flexible shielding pads on trolleys which can be moved along the frame. The assemblies allow individual pivoting movement of the pads. The pivoting movement along with the movement allowed by the trolleys provides ease of access to any point on the reactor head. The assemblies also facilitate safe and efficient mounting of the pads directly to and from storage containers such that workers have additional shielding throughout virtually the entire installation and removal process. The flexible shielding pads are designed to interleave with one another when assembled around the reactor head for substantially improved containment of radiation leakage

Oriented collagen fibers direct tumor cell intravasation

KAUST Repository

Han, Weijing; Chen, Shaohua; Yuan, Wei; Fan, Qihui; Tian, Jianxiang; Wang, Xiaochen; Chen, Longqing; Zhang, Xixiang; Wei, Weili; Liu, Ruchuan; Qu, Junle; Jiao, Yang; Austin, Robert H.; Liu, Liyu

2016-01-01

that the local fiber alignment enhanced cell-ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (∼10 mg/mL protein concentration).

Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling

Directory of Open Access Journals (Sweden)

Huang Chih-Yang

2010-10-01

Full Text Available Abstract Background Head and neck squamous cell carcinoma (HNSCC is a highly lethal cancer that contains cellular and functional heterogeneity. Previously, we enriched a subpopulation of highly tumorigenic head and neck cancer initiating cells (HN-CICs from HNSCC. However, the molecular mechanisms by which to govern the characteristics of HN-CICs remain unclear. GRP78, a stress-inducible endoplasmic reticulum chaperone, has been reported to play a crucial role in the maintenance of embryonic stem cells, but the role of GRP78 in CICs has not been elucidated. Results Initially, we recognized GRP78 as a putative candidate on mediating the stemness and tumorigenic properties of HN-CICs by differential systemic analyses. Subsequently, cells with GRP78 anchored at the plasma membrane (memGRP78+ exerted cancer stemness properties of self-renewal, differentiation and radioresistance. Of note, xenotransplantation assay indicated merely 100 memGRP78+ HNSCCs resulted in tumor growth. Moreover, knockdown of GRP78 significantly reduced the self-renewal ability, side population cells and expression of stemness genes, but inversely promoted cell differentiation and apoptosis in HN-CICs. Targeting GRP78 also lessened tumorigenicity of HN-CICs both in vitro and in vivo. Clinically, co-expression of GRP78 and Nanog predicted the worse survival prognosis of HNSCC patients by immunohistochemical analyses. Finally, depletion of GRP78 in HN-CICs induced the expression of Bax, Caspase 3, and PTEN. Conclusions In summary, memGRP78 should be a novel surface marker for isolation of HN-CICs, and targeting GRP78 signaling might be a potential therapeutic strategy for HNSCC through eliminating HN-CICs.

Early Head Start Evaluation

Data.gov (United States)

U.S. Department of Health & Human Services — Longitudinal information from an evaluation where children were randomly assigned to Early Head Start or community services as usual;direct assessments and...

The Direct Methanol Liquid-Feed Fuel Cell

Science.gov (United States)

Halpert, Gerald

1997-01-01

Until the early 1990's the idea of a practical direct methanol fuel cell from transportation and other applications was just that, an idea. Several types of fuel cells that operate under near ambient conditions were under development.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields.

Science.gov (United States)

Garcia-Cossio, Eliana; Witkowski, Matthias; Robinson, Stephen E; Cohen, Leonardo G; Birbaumer, Niels; Soekadar, Surjo R

2016-10-15

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0-4Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Stem cell clinics online: the direct-to-consumer portrayal of stem cell medicine.

Science.gov (United States)

Lau, Darren; Ogbogu, Ubaka; Taylor, Benjamin; Stafinski, Tania; Menon, Devidas; Caulfield, Timothy

2008-12-04

Despite the immature state of stem cell medicine, patients are seeking and accessing putative stem cell therapies in an "early market" in which direct-to-consumer advertising via the internet likely plays an important role. We analyzed stem cell clinic websites and appraised the relevant published clinical evidence of stem cell therapies to address three questions about the direct-to-consumer portrayal of stem cell medicine in this early market: What sorts of therapies are being offered? How are they portrayed? Is there clinical evidence to support the use of these therapies? We found that the portrayal of stem cell medicine on provider websites is optimistic and unsubstantiated by peer-reviewed literature.

Biology and immunology of cancer stem(-like) cells in head and neck cancer.

Science.gov (United States)

Qian, Xu; Ma, Chenming; Nie, Xiaobo; Lu, Jianxin; Lenarz, Minoo; Kaufmann, Andreas M; Albers, Andreas E

2015-09-01

Immunological approaches against tumors including head and neck squamous cell carcinoma (HNSCC) have been investigated for about 50 years. Such immunotherapeutic treatments are still not sufficiently effective for therapy of HNSCC. Despite the existence of immunosurveillance tumor cells may escape from the host immune system by a variety of mechanisms. Recent findings have indicated that cancer stem(-like) cells (CSCs) in HNSCC have the ability to reconstitute the heterogeneity of the bulk tumor and contribute to immunosuppression and resistance to current therapies. With regard to the CSC model, future immunotherapy possibly in combination with other modes of treatment should target this subpopulation specifically to reduce local recurrence and metastasis. In this review, we will summarize recent research findings on immunological features of CSCs and the potential of immune targeting of CSCs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Erythropoietin receptor is not a surrogate marker for tumor hypoxia and does not correlate with survival in head and neck squamous cell carcinomas.

NARCIS (Netherlands)

Hoogsteen, I.J.; Peeters, W.J.M.; Marres, H.A.M.; Rijken, P.F.J.W.; Hoogen, F.J.A. van den; Kogel, A.J. van der; Kaanders, J.H.A.M.

2005-01-01

BACKGROUND AND PURPOSE: To evaluate erythropoietin receptor (EPOR) expression in human head and neck squamous cell carcinomas and correlate this to the presence of tumor hypoxia and treatment outcome. PATIENTS AND METHODS: Eighty-five patients with locally advanced tumors of the head and neck were

Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma

Science.gov (United States)

Setúbal Destro Rodrigues, Maria Fernanda; Gammon, Luke; Rahman, Muhammad M.; Biddle, Adrian; Nunes, Fabio Daumas; Mackenzie, Ian C.

2018-01-01

The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies. PMID:29568372

Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma.

Science.gov (United States)

Setúbal Destro Rodrigues, Maria Fernanda; Gammon, Luke; Rahman, Muhammad M; Biddle, Adrian; Nunes, Fabio Daumas; Mackenzie, Ian C

2018-03-02

The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies.

Stem cell monitoring with a direct or indirect labeling method

Energy Technology Data Exchange (ETDEWEB)

Kim, Min Hwan; Lee, Yong Jin [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul (Korea, Republic of)

2016-12-15

The molecular imaging techniques allow monitoring of the transplanted cells in the same individuals over time, from early localization to the survival, migration, and differentiation. Generally, there are two methods of stem cell labeling: direct and indirect labeling methods. The direct labeling method introduces a labeling agent into the cell, which is stably incorporated or attached to the cells prior to transplantation. Direct labeling of cells with radionuclides is a simple method with relatively fewer adverse events related to genetic responses. However, it can only allow short-term distribution of transplanted cells because of the decreasing imaging signal with radiodecay, according to the physical half-lives, or the signal becomes more diffuse with cell division and dispersion. The indirect labeling method is based on the expression of a reporter gene transduced into the cell before transplantation, which is then visualized upon the injection of an appropriate probe or substrate. In this review, various imaging strategies to monitor the survival and behavior change of transplanted stem cells are covered. Taking these new approaches together, the direct and indirect labeling methods may provide new insights on the roles of in vivo stem cell monitoring, from bench to bedside.

Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: a systematic review

International Nuclear Information System (INIS)

Swartz, Justin E; Pothen, Ajit J; Stegeman, Inge; Willems, Stefan M; Grolman, Wilko

2015-01-01

Awareness increases that the tumor biology influences treatment outcome and prognosis in cancer. Tumor hypoxia is thought to decrease sensitivity to radiotherapy and some forms of chemotherapy. Presence of hypoxia may be assessed by investigating expression of endogenous markers of hypoxia (EMH) using immunohistochemistry (IHC). In this systematic review we investigated the effect of EMH expression on local control and survival according to treatment modality in head and neck cancer (head and neck squamous cell carcinoma [HNSCC]). A search was performed in MEDLINE and EMBASE. Studies were eligible for inclusion that described EMH expression in relation to outcome in HNSCC patients. Quality was assessed using the Quality in Prognosis Studies (QUIPS) tool. Hazard ratios for locoregional control and survival were extracted. Forty studies of adequate quality were included. HIF-1a, HIF-2a, CA-IX, GLUT-1, and OPN were identified as the best described EMHs. With exception of HIF-2a, all EMHs were significantly related to adverse outcome in multiple studies, especially in studies where patients underwent single-modality treatment. Positive expression was often correlated with adverse clinical characteristics, including disease stage and differentiation grade. In summary, EMH expression was common in HNSCC patients and negatively influenced their prognosis. Future studies should investigate the effect of hypoxia-modified treatment schedules in patients with high In summary, EMH expression. These may include ARCON, treatment with nimorazole, or novel targeted therapies directed at hypoxic tissue. Also, the feasibility of surgical removal of the hypoxic tumor volume prior to radiotherapy should be investigated

Impact of total radiotherapy dose on survival for head and neck Merkel cell carcinoma after resection.

Science.gov (United States)

Patel, Sagar A; Qureshi, Muhammad M; Mak, Kimberley S; Sahni, Debjani; Giacalone, Nicholas J; Ezzat, Waleed; Jalisi, Scharukh; Truong, Minh Tam

2017-07-01

Head and neck Merkel cell carcinoma (MCC) is commonly treated with surgery and adjuvant radiotherapy (RT) for high-risk features. The optimal radiation dose is unknown. One thousand six hundred twenty-five eligible patients with head and neck MCC were identified in the National Cancer Data Base (NCDB). Radiation dose was divided into 3 groups: 30 to 55-70 Gy. Cox regression was used to compare overall survival (OS) between groups, accounting for age, sex, stage, surgery type, margin status, comorbidities, and use of chemotherapy. With a median follow-up of 33.5 months, 3-year OS was 48.9%, 70.3%, and 58.7% for 30 to 55-70 Gy, respectively (P 55-70 Gy (adjusted HR 1.21; 95% CI 1.0-1.46; P = .06) were associated with worse survival. Adjuvant radiation doses within 50-55 Gy may be optimal for head and neck MCC. © 2017 Wiley Periodicals, Inc.

Gastroesophageal reflux disease and odds of head and neck squamous cell carcinoma in North Carolina.

Science.gov (United States)

Busch, Evan L; Zevallos, Jose P; Olshan, Andrew F

2016-05-01

Exposure to excess gastric acid resulting from gastroesophageal reflux disease, also known as acid reflux or heartburn, might contribute to initiation of head and neck squamous cell carcinoma, particularly laryngeal cancer. Prior epidemiologic studies have reported inconsistent results. We sought to clarify this relationship using an observational study with a larger available sample size and better-characterized exposure information than most prior studies. A population-based case-control study of head and neck cancer in North Carolina with 1,340 newly diagnosed cases and 1,378 controls matched on age, race, and sex. We used unconditional logistic regression to examine associations between self-reported heartburn and development of overall head and neck cancer as well as development of cancer at specific tumor sites. Subgroup analysis by smoking and alcoholic drinking status was used to make comparisons with a previous study that used a similar study design. Overall, an increased odds of head and neck cancer was not associated with either self-reported history of heartburn symptoms (odds ratio = 0.85; 95% confidence interval 0.68, 1.06) or self-reported medical diagnosis of GERD (OR = 0.89; 95% CI 0.71, 1.11). These patterns held for specific tumor sites. For laryngopharyngeal cancer, we did not detect any associations regardless of joint smoking and alcoholic drinking status. Gastroesophageal reflux does not appear to play a role in development of head and neck cancer. 3b. Laryngoscope, 126:1091-1096, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

The human HECA interacts with cyclins and CDKs to antagonize Wnt-mediated proliferation and chemoresistance of head and neck cancer cells

Energy Technology Data Exchange (ETDEWEB)

Dowejko, Albert, E-mail: Albert.Dowejko@klinik.uni-regensburg.de [Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg (Germany); Bauer, Richard; Bauer, Karin [Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg (Germany); Mueller-Richter, Urs D.A. [Department of Oral and Maxillofacial Plastic Surgery, University of Wuerzburg, Pleicherwall 2, 97070 Wuerzburg (Germany); Reichert, Torsten E. [Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg (Germany)

2012-03-10

There is a growing evidence that the human homologue of the Drosophila headcase (HECA) plays an important role in human carcinogenesis. So far specific protein interaction partners and affected signaling pathways of HECA are still elusive. In a recent study we showed that HECA overexpression in oral squamous-cell carcinoma (OSCC) keratinocytes has tumor suppressive effects resulting in a recuperation of cell cycle control concerning the entry and progression of S-phase, G2- and M-phase. Currently, quantitative RT-PCR and immunohistochemical analysis of primary tumor tissue from OSCC patients demonstrate that HECA expression is markedly decreased compared to normal control patients with abundant HECA expression. Additionally, there is nearly no HECA expression in OSCC metastases. Here, we show that HECA expression is negatively controlled by the Wnt-pathway and TCF4, a Wnt related transcription factor, binds to the HECA promoter. Furthermore, immunocytochemistry reveals colocalization of HECA with the cyclin dependent kinase CDK9. Immunoprecipitation experiments and proximity ligation assays further reveal an interaction of HECA with CDK2, CDK9, Cyclin A and Cyclin K, a direct transcriptional target of the p53 tumor suppressor. Silencing HECA in OSCC cell lines leads to a significant increase of cell division and a markedly increased resistance against the chemotherapeutic cisplatin. On the contrary, HECA overexpressing OSCC cell lines show decreased resistance of OSCC cells against cisplatin. Therefore, HECA could be considered as future therapeutic agent against Wnt-dependent tumor progression. -- Highlights: Black-Right-Pointing-Pointer HECA is a new cell cycle regulator with anti-tumor features in head and neck cancer. Black-Right-Pointing-Pointer During tumor progression HECA mRNA and protein expression decrease. Black-Right-Pointing-Pointer The HECA promotor is a direct target of the Wnt/beta-catenin/TCF-pathway. Black-Right-Pointing-Pointer The HECA protein

Allosteric conformational barcodes direct signaling in the cell.

Science.gov (United States)

Nussinov, Ruth; Ma, Buyong; Tsai, Chung-Jung; Csermely, Peter

2013-09-03

The cellular network is highly interconnected. Pathways merge and diverge. They proceed through shared proteins and may change directions. How are cellular pathways controlled and their directions decided, coded, and read? These questions become particularly acute when we consider that a small number of pathways, such as signaling pathways that regulate cell fates, cell proliferation, and cell death in development, are extensively exploited. This review focuses on these signaling questions from the structural standpoint and discusses the literature in this light. All co-occurring allosteric events (including posttranslational modifications, pathogen binding, and gain-of-function mutations) collectively tag the protein functional site with a unique barcode. The barcode shape is read by an interacting molecule, which transmits the signal. A conformational barcode provides an intracellular address label, which selectively favors binding to one partner and quenches binding to others, and, in this way, determines the pathway direction, and, eventually, the cell's response and fate. Copyright © 2013 Elsevier Ltd. All rights reserved.

Modelling Effects on Grid Cells of Sensory Input During Self-motion

Science.gov (United States)

2016-04-20

individual oscillators. These oscillatory interference models effectively simulate the theta rhythmic firing of grid cells (Hafting et al. 2008; Jeewajee...et al. 2008; Brandon et al. 2011; Koenig et al. 2011; Stensola et al. 2012), and the changes in rhythmic firing frequency based on running speed and...Fiete, 2009; Couey et al. 2013), and equate head direction with movement direction. However, an analysis of behavioural data shows that the head

Direct lifts of coupled cell networks

Science.gov (United States)

Dias, A. P. S.; Moreira, C. S.

2018-04-01

In networks of dynamical systems, there are spaces defined in terms of equalities of cell coordinates which are flow-invariant under any dynamical system that has a form consistent with the given underlying network structure—the network synchrony subspaces. Given a network and one of its synchrony subspaces, any system with a form consistent with the network, restricted to the synchrony subspace, defines a new system which is consistent with a smaller network, called the quotient network of the original network by the synchrony subspace. Moreover, any system associated with the quotient can be interpreted as the restriction to the synchrony subspace of a system associated with the original network. We call the larger network a lift of the smaller network, and a lift can be interpreted as a result of the cellular splitting of the smaller network. In this paper, we address the question of the uniqueness in this lifting process in terms of the networks’ topologies. A lift G of a given network Q is said to be direct when there are no intermediate lifts of Q between them. We provide necessary and sufficient conditions for a lift of a general network to be direct. Our results characterize direct lifts using the subnetworks of all splitting cells of Q and of all split cells of G. We show that G is a direct lift of Q if and only if either the split subnetwork is a direct lift or consists of two copies of the splitting subnetwork. These results are then applied to the class of regular uniform networks and to the special classes of ring networks and acyclic networks. We also illustrate that one of the applications of our results is to the lifting bifurcation problem.

Autophagy induction contributes to GDC-0349 resistance in head and neck squamous cell carcinoma (HNSCC) cells

Energy Technology Data Exchange (ETDEWEB)

Zhou, Yajuan; Peng, Yi [Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan (China); Tang, Hao [Department of Pathology, Hubei Cancer Hospital, Wuhan 430071 (China); He, Xiaojun; Wang, Zhaohua [Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan (China); Hu, Desheng, E-mail: hudeshengvvip@sina.com [Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan (China); Zhou, Xiaoyi, E-mail: zhouxy1218@126.com [Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan (China)

2016-08-19

Dysregulation of mammalian target of rapamycin (mTOR) signaling contributes to head and neck squamous cell carcinoma (HNSCC) tumorigenesis and progression. In the current study, we tested the anti-HNSCC cell activity by GDC-0349, a selective ATP-competitive inhibitor of mTOR. We showed that GDC-0349 inhibited proliferation of established and primary human HNSCC cells bearing high-level of p-AKT/p-S6K. Further, it induced caspase-dependent apoptosis in the HNSCC cells. GDC-0349 blocked mTORC1 and mTORC2 activation, yet it simultaneously induced autophagy activation in HNSCC cells. The latter was evidenced by induction of LC3B-II, Beclin-1 and Autophagy-related (ATG)-7, as well as downregulation of p62. Autophagy inhibitors (3-methyladenine and bafilomycin A1) or ATG-7 siRNA dramatically potentiated GDC-0349’s cytotoxicity against HNSCC cells. Intriguingly, we showed that ceramide (C14), a pro-apoptotic sphingolipid, also induced ATG-7 degradation, and sensitized HNSCC cells to GDC-0349. Collectively, the preclinical study provided evidences to support GDC-0349 as a promising anti-HNSCC agent. GDC-0349 sensitization may be achieved via autophagy inhibition. - Highlights: • GDC-0349 inhibits proliferation of HNSCC cells bearing high-level of p-AKT/p-S6K. • GDC-0349 activates caspase-dependent apoptosis in HNSCC cells. • Simultaneous blockage of mTORC1/2 by GDC-0349 induces autophagy activation. • Autophagy inhibitor or ATG-7 siRNA potentiates GDC-0349’s cytotoxicity. • C14 ceramide downregulates ATG-7 and sensitizes HNSCC cells to GDC-0349.

Establishment and characterization of a novel head and neck squamous cell carcinoma cell line USC-HN1.

Science.gov (United States)

Liebertz, Daniel J; Lechner, Melissa G; Masood, Rizwan; Sinha, Uttam K; Han, Jing; Puri, Raj K; Correa, Adrian J; Epstein, Alan L

2010-02-22

Head and neck squamous cell carcinoma (HNSCC) is an aggressive and lethal malignancy. Publically available cell lines are mostly of lingual origin, or have not been carefully characterized. Detailed characterization of novel HNSCC cell lines is needed in order to provide researchers a concrete keystone on which to build their investigations. The USC-HN1 cell line was established from a primary maxillary HNSCC biopsy explant in tissue culture. The immortalized cells were then further characterized by heterotransplantation in Nude mice; immunohistochemical staining for relevant HNSCC biomarkers; flow cytometry for surface markers; cytogenetic karyotypic analysis; human papillomavirus and Epstein-Barr virus screening; qRT-PCR for oncogene and cytokine analysis; investigation of activated, cleaved Notch1 levels; and detailed 35,000 gene microarray analysis. Characterization experiments confirmed the human HNSCC origin of USC-HN1, including a phenotype similar to the original tumor. Viral screening revealed no HPV or EBV infection, while western blotting displayed significant upregulation of activated, cleaved Notch1. USC-HN1, a novel immortalized cell line has been derived from a maxillary HNSCC. Characterization studies have shown that the cell line is of HNSCC origin and displays many of the same markers previously reported in the literature. USC-HN1 is available for public research and will further the investigation of HNSCC and the development of new therapeutic modalities.

Development of new membrane materials for direct methanol fuel cells

NARCIS (Netherlands)

Yildirim, M.H.

2009-01-01

Development of new membrane materials for direct methanol fuel cells Direct methanol fuel cells (DMFCs) can convert the chemical energy of a fuel directly into electrical energy with high efficiency and low emission of pollutants. DMFCs can be used as the power sources to portable electronic devices

Primary histiocytic sarcoma arising in the head and neck with predominant spindle cell component

Directory of Open Access Journals (Sweden)

Zhao XF

2007-02-01

Full Text Available Abstract This is the first case report of Histiocytic Sarcoma (HS with predominant spindle cell component occurring in the head and neck region of a 41-year-old man. The tumor was composed of sheets of large round to oval cells with pleomorphic vesicular nuclei, prominent nucleoli and abundant eosinophilic cytoplasm. Multinucleated forms, numerous mitoses, and tumor necrosis were also noted. Sheets, fascicles, and whorls of spindle cells with spindled to ovoid vesicular nuclei, small to medium-sized distinct nucleoli, and eosinophilic cytoplasm were frequently observed. Immunohistochemical staining in the tumor cells was positive for CD163, CD68, lysozyme, CD45, and NSE. Focal expression of CD4 and S-100 was also noted. Electron microscopy demonstrated an abundance of lysosomes in the cytoplasm of tumor cells. Chromosome study revealed a 57–80 hyperdiploid [7]/46, XY [13] karyotype, including 3 to 4 copies of various chromosomes. The immunohistochemical and ultrastructural findings confirmed the diagnosis of HS.

Starclose SE® hemostasis after 6F direct antegrade superficial femoral artery access distal to the femoral head for peripheral endovascular procedures in obese patients.

Science.gov (United States)

Spiliopoulos, Stavros; Kitrou, Panagiotis; Christeas, Nikolaos; Karnabatidis, Dimitris

2016-01-01

Direct superficial femoral artery (SFA) antegrade puncture is a valid alternative to common femoral artery (CFA) access for peripheral vascular interventions. Data investigating vascular closure device (VCD) hemostasis of distant SFA 6F access are limited. We aimed to investigate the safety and effectiveness of the Starclose SE® VCD for hemostasis, following direct 6F antegrade SFA access distal to the femoral head. This prospective, single-center study included patients who were not suitable for CFA puncture and were scheduled to undergo peripheral endovascular interventions using direct antegrade SFA 6F access, at least 2 cm below the inferior edge of femoral head. Hemostasis was obtained with the Starclose SE® VCD (Abbott Laboratories). Primary endpoints were successful hemostasis rate and periprocedural (30-day) major complication rate. Secondary endpoint was the rate of minor complications. Clinical and Doppler ultrasound follow-up was performed at discharge and at one month. Between September 2014 and August 2015, a total of 30 patients (21 male; 70.0%) with a mean body mass index of 41.2 kg/m2 were enrolled. Mean age was 72±9 years (range, 67-88 years). Most patients suffered from critical limb ischemia (87.1%) and diabetes (61.3%). Calcifications were present in eight cases (26.6%). Reason for direct SFA puncture was obesity (100%). Successful hemostasis was achieved in 100% of the cases. No major complications were noted after one-month follow-up. Minor complications included two <5 cm hematomas (6.6%) not necessitating treatment. In this prospective study, Starclose SE® VCD was safe and effective for hemostasis of antegrade direct SFA puncture. Uncomplicated hemostasis was achieved even in cases of puncturing 2 to 7 cm below the inferior edge of the femoral head.

Reolysin and Histone Deacetylase Inhibition in the Treatment of Head and Neck Squamous Cell Carcinoma

Directory of Open Access Journals (Sweden)

Alena C. Jaime-Ramirez

2017-06-01

Full Text Available Oncolytic viruses (OVs are emerging as powerful anti-cancer agents and are currently being tested for their safety and efficacy in patients. Reovirus (Reolysin, a naturally occurring non-pathogenic, double-stranded RNA virus, has natural oncolytic activity and is being tested in phase I–III clinical trials in a variety of tumor types. With its recent US Food and Drug Administration (FDA orphan drug designation for several tumor types, Reolysin is a potential therapeutic agent for various cancers, including head and neck squamous cell carcinomas (HNSCCs, which have a 5-year survival of ∼55%. Histone deacetylase inhibitors (HDACis comprise a structurally diverse class of compounds with targeted anti-cancer effects. The first FDA-approved HDACi, vorinostat (suberoylanilide hydroxamic acid [SAHA], is currently being tested in patients with head and neck cancer. Recent findings indicate that HDAC inhibition in myeloma cells results in the upregulation of the Reolysin entry receptor, junctional adhesion molecule 1 (JAM-1, facilitating reovirus infection and tumor cell killing both in vitro and in vivo. In this study, we tested the anti-tumor efficacy of HDAC inhibitors AR-42 or SAHA in conjunction with Reolysin in HNSCCs. While HDAC inhibition increased JAM-1 and reovirus entry, the impact of this combination therapy was tested on the development of anti-tumor immune responses.

How the Relationship between Text and Headings Influences Readers' Memory

Science.gov (United States)

Ritchey, Kristin; Schuster, Jonathan; Allen, Jaryn

2008-01-01

Two questions regarding signals' influence on memory were examined. First, the relationship between headings and text was manipulated to determine whether headings serve as visual cues, directing readers to recall all subsequent information, or content-specific cues, directing readers to recall only to certain information. Second, distance between…

The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neck

DEFF Research Database (Denmark)

Nylander, K.; Dabelsteen, Erik; Hall, P.A.

2000-01-01

and poor patient outcome was found when looking only at patients with laryngeal squamous cell carcinomas. Also, in oral premalignant lesions, expression of p53-positive cells in the suprabasal layers of the epithelium has been seen as an indication of impending malignant development. Concerning......Despite intense research, the 5-year survival rate for patients with squamous cell carcinoma of the head and neck (SCCHN) is still low. Several different factors have been studied in the search for one or more factors that give important prognostic information at the time of diagnosis. Many recent...

Clinical Evaluation of Direct Aperture Optimization When Applied to Head-And-Neck IMRT

International Nuclear Information System (INIS)

Jones, Stephen; Williams, Matthew

2008-01-01

Direct Machine Parameter Optimization (DMPO) is a leaf segmentation program released as an optional item of the Pinnacle planning system (Philips Radiation Oncology Systems, Milpitas, CA); it is based on the principles of direct aperture optimization where the size, shape, and weight of individual segments are optimized to produce an intensity modulated radiation treatment (IMRT) plan. In this study, we compare DMPO to the traditional method of IMRT planning, in which intensity maps are optimized prior to conversion into deliverable multileaf collimator (MLC) apertures, and we determine if there was any dosimetric improvement, treatment efficiency gain, or planning advantage provided by the use of DMPO. Eleven head-and-neck patients treated with IMRT had treatment plans generated using each optimization method. For each patient, the same planning parameters were used for each optimization method. All calculations were performed using Pinnacle version 7.6c software and treatments were delivered using a step-and-shoot IMRT method on a Varian 2100EX linear accelerator equipped with a 120-leaf Millennium MLC (Varian Medical Systems, Palo Alto, CA). Each plan was assessed based on the calculation time, a conformity index, the composite objective value used in the optimization, the number of segments, monitor units (MUs), and treatment time. The results showed DMPO to be superior to the traditional optimization method in all areas. Considerable advantages were observed in the dosimetric quality of DMPO plans, which also required 32% less time to calculate, 42% fewer MUs, and 35% fewer segments than the conventional optimization method. These reductions translated directly into a 29% decrease in treatment times. While considerable gains were observed in planning and treatment efficiency, they were specific to our institution, and the impact of direct aperture optimization on plan quality and workflow will be dependent on the planning parameters, planning system, and

Chemovirotherapy for head and neck squamous cell carcinoma with EGFR-targeted and CD/UPRT-armed oncolytic measles virus.

Science.gov (United States)

Zaoui, K; Bossow, S; Grossardt, C; Leber, M F; Springfeld, C; Plinkert, P K; Kalle, C von; Ungerechts, G

2012-03-01

First-line treatment of recurrent and/or refractory head and neck squamous cell carcinoma (HNSCC) is based on platinum, 5-fluorouracil (5-FU) and the monoclonal antiEGFR antibody cetuximab. However, in most cases this chemoimmunotherapy does not cure the disease, and more than 50% of HNSCC patients are dying because of local recurrence of the tumors. In the majority of cases, HNSCC overexpress the epidermal growth factor receptor (EGFR), and its presence is associated with a poor outcome. In this study, we engineered an EGFR-targeted oncolytic measles virus (MV), armed with the bifunctional enzyme cytosine deaminase/uracil phosphoribosyltransferase (CD/UPRT). CD/UPRT converts 5-fluorocytosine (5-FC) into the chemotherapeutic 5-FU, a mainstay of HNSCC chemotherapy. This virus efficiently replicates in and lyses primary HNSCC cells in vitro. Arming with CD/UPRT mediates efficient prodrug activation with high bystander killing of non-infected tumor cells. In mice bearing primary HNSCC xenografts, intratumoral administration of MV-antiEGFR resulted in statistically significant tumor growth delay and prolongation of survival. Importantly, combination with 5-FC is superior to virus-only treatment leading to significant tumor growth inhibition. Thus, chemovirotherapy with EGFR-targeted and CD/UPRT-armed MV is highly efficacious in preclinical settings with direct translational implications for a planned Phase I clinical trial of MV for locoregional treatment of HNSCC.

Engineering the human pluripotent stem cell microenvironment to direct cell fate.

Science.gov (United States)

Hazeltine, Laurie B; Selekman, Joshua A; Palecek, Sean P

2013-11-15

Human pluripotent stem cells (hPSCs), including both embryonic stem cells and induced pluripotent stem cells, offer a potential cell source for research, drug screening, and regenerative medicine applications due to their unique ability to self-renew or differentiate to any somatic cell type. Before the full potential of hPSCs can be realized, robust protocols must be developed to direct their fate. Cell fate decisions are based on components of the surrounding microenvironment, including soluble factors, substrate or extracellular matrix, cell-cell interactions, mechanical forces, and 2D or 3D architecture. Depending on their spatio-temporal context, these components can signal hPSCs to either self-renew or differentiate to cell types of the ectoderm, mesoderm, or endoderm. Researchers working at the interface of engineering and biology have identified various factors which can affect hPSC fate, often based on lessons from embryonic development, and they have utilized this information to design in vitro niches which can reproducibly direct hPSC fate. This review highlights culture systems that have been engineered to promote self-renewal or differentiation of hPSCs, with a focus on studies that have elucidated the contributions of specific microenvironmental cues in the context of those culture systems. We propose the use of microsystem technologies for high-throughput screening of spatial-temporal presentation of cues, as this has been demonstrated to be a powerful approach for differentiating hPSCs to desired cell types. Copyright © 2013 Elsevier Inc. All rights reserved.

Overexpression of EMMPRIN isoform 2 is associated with head and neck cancer metastasis.

Directory of Open Access Journals (Sweden)

Zhiquan Huang

Full Text Available Extracellular matrix metalloproteinase inducer (EMMPRIN, a plasma membrane protein of the immunoglobulin (Ig superfamily, has been reported to promote cancer cell invasion and metastasis in several human malignancies. However, the roles of the different EMMPRIN isoforms and their associated mechanisms in head and neck cancer progression remain unknown. Using quantitative real-time PCR, we found that EMMPRIN isoform 2 (EMMPRIN-2 was the only isoform that was overexpressed in both head and neck cancer tissues and cell lines and that it was associated with head and neck cancer metastasis. To determine the effects of EMMPRIN-2 on head and neck cancer progression, we transfected head and neck cancer cells with an EMMPRIN-2 expression vector and EMMPRIN-2 siRNA to exogenously modulate EMMPRIN-2 expression and examined the functional importance of EMMPRIN-2 in head and neck cancer invasion and metastasis. We found that EMMPRIN-2 promoted head and neck cancer cell invasion, migration, and adhesion in vitro and increased lung metastasis in vivo. Mechanistic studies revealed that EMMPRIN-2 overexpression promoted the secretion of extracellular signaling molecules, including matrix metalloproteinases-2(MMP-2, urokinase-type plasminogen activator(uPA and Cathepsin B, in head and neck cancer cells. While MMP-2 and uPA have been demonstrated to be important mediators of EMMPRIN signaling, the role of Cathepsin B in EMMPRIN-mediated molecular cascades and tumorigenesis has not been established. We found that EMMPRIN-2 overexpression and Cathepsin B down-regulation significantly inhibited the invasion, migration and adhesion of Tca8133 cells, suggesting that Cathepsin B is required for EMMPRIN-2 enhanced cell migration and invasion in head and neck cancer. The results of our study demonstrate the important role of EMMPRIN-2 in head and neck cancer progression for the first time and reveal that increased extracellular secretion of Cathepsin B may be a novel

Overexpression of EMMPRIN isoform 2 is associated with head and neck cancer metastasis.

Science.gov (United States)

Huang, Zhiquan; Tan, Ning; Guo, Weijie; Wang, Lili; Li, Haigang; Zhang, Tianyu; Liu, Xiaojia; Xu, Qin; Li, Jinsong; Guo, Zhongmin

2014-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN), a plasma membrane protein of the immunoglobulin (Ig) superfamily, has been reported to promote cancer cell invasion and metastasis in several human malignancies. However, the roles of the different EMMPRIN isoforms and their associated mechanisms in head and neck cancer progression remain unknown. Using quantitative real-time PCR, we found that EMMPRIN isoform 2 (EMMPRIN-2) was the only isoform that was overexpressed in both head and neck cancer tissues and cell lines and that it was associated with head and neck cancer metastasis. To determine the effects of EMMPRIN-2 on head and neck cancer progression, we transfected head and neck cancer cells with an EMMPRIN-2 expression vector and EMMPRIN-2 siRNA to exogenously modulate EMMPRIN-2 expression and examined the functional importance of EMMPRIN-2 in head and neck cancer invasion and metastasis. We found that EMMPRIN-2 promoted head and neck cancer cell invasion, migration, and adhesion in vitro and increased lung metastasis in vivo. Mechanistic studies revealed that EMMPRIN-2 overexpression promoted the secretion of extracellular signaling molecules, including matrix metalloproteinases-2(MMP-2), urokinase-type plasminogen activator(uPA) and Cathepsin B, in head and neck cancer cells. While MMP-2 and uPA have been demonstrated to be important mediators of EMMPRIN signaling, the role of Cathepsin B in EMMPRIN-mediated molecular cascades and tumorigenesis has not been established. We found that EMMPRIN-2 overexpression and Cathepsin B down-regulation significantly inhibited the invasion, migration and adhesion of Tca8133 cells, suggesting that Cathepsin B is required for EMMPRIN-2 enhanced cell migration and invasion in head and neck cancer. The results of our study demonstrate the important role of EMMPRIN-2 in head and neck cancer progression for the first time and reveal that increased extracellular secretion of Cathepsin B may be a novel mechanism

San andreas fault zone head waves near parkfield, california.

Science.gov (United States)

Ben-Zion, Y; Malin, P

1991-03-29

Microearthquake seismograms from the borehole seismic network on the San Andreas fault near Parkfield, California, provide three lines of evidence that first P arrivals are "head" waves refracted along the cross-fault material contrast. First, the travel time difference between these arrivals and secondary phases identified as direct P waves scales linearly with the source-receiver distance. Second, these arrivals have the emergent wave character associated in theory and practice with refracted head waves instead of the sharp first breaks associated with direct P arrivals. Third, the first motion polarities of the emergent arrivals are reversed from those of the direct P waves as predicted by the theory of fault zone head waves for slip on the San Andreas fault. The presence of fault zone head waves in local seismic network data may help account for scatter in earthquake locations and source mechanisms. The fault zone head waves indicate that the velocity contrast across the San Andreas fault near Parkfield is approximately 4 percent. Further studies of these waves may provide a way of assessing changes in the physical state of the fault system.

GLYCAN-DIRECTED CAR-T CELLS.

Science.gov (United States)

Steentoft, Catharina; Migliorini, Denis; King, Tiffany R; Mandel, Ulla; June, Carl H; Posey, Avery D

2018-01-23

Cancer immunotherapy is rapidly advancing in the treatment of a variety of hematopoietic cancers, including pediatric acute lymphoblastic leukemia and diffuse large B cell lymphoma, with chimeric antigen receptor (CAR)-T cells. CARs are genetically encoded artificial T cell receptors that combine the antigen specificity of an antibody with the machinery of T cell activation. However, implementation of CAR technology in the treatment of solid tumors has been progressing much slower. Solid tumors are characterized by a number of challenges that need to be overcome, including cellular heterogeneity, immunosuppressive tumor microenvironment (TME), and, in particular, few known cancer-specific targets. Post-translational modifications that differentially occur in malignant cells generate valid cell surface, cancer-specific targets for CAR-T cells. We previously demonstrated that CAR-T cells targeting an aberrant O-glycosylation of MUC1, a common cancer marker associated with changes in cell adhesion, tumor growth, and poor prognosis, could control malignant growth in mouse models. Here, we discuss the field of glycan-directed CAR-T cells and review the different classes of antibodies specific for glycan-targeting, including the generation of high affinity O-glycopeptide antibodies. Finally, we discuss historic and recently investigated glycan targets for CAR-T cells and provide our perspective on how targeting the tumor glycoproteome and/or glycome will improve CAR-T immunotherapy. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells.

Science.gov (United States)

Kaitsuka, Taku; Tomizawa, Kazuhito

2015-11-06

Protein transduction using cell-penetrating peptides (CPPs) is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS) cells, directing the differentiation into specific cell types and supporting gene editing/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies.

Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells

Directory of Open Access Journals (Sweden)

Taku Kaitsuka

2015-11-01

Full Text Available Protein transduction using cell-penetrating peptides (CPPs is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS cells, directing the differentiation into specific cell types and supporting gene editing/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies.

T-cell chronic lymphocytic leukemia in a double yellow-headed Amazon parrot (Amazona ochrocephala oratrix).

Science.gov (United States)

Osofsky, Anna; Hawkins, Michelle G; Foreman, Oded; Kent, Michael S; Vernau, William; Lowenstine, Linda J

2011-12-01

An adult, male double yellow-headed Amazon parrot (Amazona ochrocephala oratrix) was diagnosed with chronic lymphocytic leukemia based on results of a complete blood cell count and cytologic examination of a bone marrow aspirate. Treatment with oral chlorambucil was attempted, but no response was evident after 40 days. The bird was euthanatized, and the diagnosis of chronic lymphocytic leukemia was confirmed on gross and microscopic examination of tissues. Neoplastic lymphocytes were found in the bone marrow, liver, kidney, testes, and blood vessels. Based on CD3-positive immunocytochemical and immunohistochemical immunophenotyping, the chronic lymphocytic leukemia was determined to be of T-cell origin.

Phase II study of cetuximab plus concomitant boost radiotherapy in Japanese patients with locally advanced squamous cell carcinoma of the head and neck

International Nuclear Information System (INIS)

Okano, Susumu; Yoshino, Takayuki; Fujii, Masato

2013-01-01

We investigated the tolerability of cetuximab plus radiotherapy in Japanese patients with untreated locally advanced squamous cell carcinoma of the head and neck. Patients with epidermal growth factor receptor-expressing locally advanced squamous cell carcinoma of the head and neck received cetuximab (400 mg/m 2 initial dose then 250 mg/m 2 weekly) for 7 weeks plus concomitant boost radiotherapy (weeks 2-7: once daily [1.8 Gy] for 3.6 weeks, then twice daily [1.8 Gy morning and 1.5 Gy afternoon] for 2.4 weeks). The primary endpoint was treatment completion rate (the rate of treated patients completing ≥70% of the planned cetuximab dose and the full dose of radiotherapy within 2 weeks over the planned schedule). Twenty-two patients were evaluable. The treatment completion rate was 100% (95% confidence interval 85-100). The response rate 8 weeks post-radiotherapy was 82% (95% confidence interval 60-95). The most common grade 3/4 treatment-emergent adverse events were mucosal inflammation (73%); dermatitis (27%); and infection, radiation skin injury and stomatitis (23% each). Cetuximab plus concomitant boost radiotherapy can be safely administered to Japanese patients with locally advanced squamous cell carcinoma of the head and neck. Tolerability and efficacy were in line with those reported in the Phase III Bonner trial in a Western population of patients with locally advanced squamous cell carcinoma of the head and neck. (author)

Docetaxel in the treatment of squamous cell carcinoma of the head and neck

Directory of Open Access Journals (Sweden)

Alexander Rapidis

2008-11-01

Full Text Available Alexander Rapidis1, Nicholas Sarlis2, Jean-Louis Lefebvre3, Merrill Kies41Department of Maxillofacial Surgery, Greek Anticancer Institute, Saint Savvas Hospital, Athens, Greece; 2Department of Medical Affairs, Oncology – US Sanofi-Aventis, Bridgewater, NJ, USA; 3Head and Neck Department, Centre Régional de Lutte Contre le Cancer de Lille, Lille, France; 4Department of Thoracic/Head and Neck Medical Oncology, The University of Texas – M.D. Anderson Cancer Center, Houston, TX, USAAbstract: Squamous cell carcinoma of the head and neck (SCCHN presents at a locally advanced (LA stage in many patients. Chemotherapy has been successfully integrated into first-line treatment programs, either during or prior to radiotherapy (RT – the cornerstone modality for local disease control of inoperable disease or when organ preservation is desired. Concomitant chemoradiotherapy (CCRT provides an absolute survival benefit when compared with other types of locoregional therapy that exclude chemotherapy. Nonetheless, distant metastases still represent the most common cause of treatment failure. Consequently, adding induction chemotherapy (ICT to definitive non-surgical local therapies with a curative intent has been vigorously explored in LA SCCHN. Recently, it has been shown that ICT using the combination of the taxane docetaxel with cisplatin–5-fluorouracil provides significant survival benefit over cisplatin–5-FU, when used before either definitive RT (TAX323 trial or carboplatin-based CCRT (TAX324 trial. Docetaxel is also being investigated in metastatic or recurrent (M/R disease, with promising initial results. It is very likely that the future management strategies of SCCHN will incorporate biologic agents as an add-on to docetaxel-containing schemas, administered either as ICT prior to CCRT in the LA setting or for the management of M/R disease.Keywords: chemoradiotherapy, chemotherapy, docetaxel, head and neck carcinoma, induction, locally

Rate dependent direct inverse hysteresis compensation of piezoelectric micro-actuator used in dual-stage hard disk drive head positioning system.

Science.gov (United States)

Rahman, Md Arifur; Al Mamun, Abdullah; Yao, Kui

2015-08-01

The head positioning servo system in hard disk drive is implemented nowadays using a dual-stage actuator—the primary stage consisting of a voice coil motor actuator providing long range motion and the secondary stage controlling the position of the read/write head with fine resolution. Piezoelectric micro-actuator made of lead zirconate titanate (PZT) has been a popular choice for the secondary stage. However, PZT micro-actuator exhibits hysteresis—an inherent nonlinear characteristic of piezoelectric material. The advantage expected from using the secondary micro-actuator is somewhat lost by the hysteresis of the micro-actuator that contributes to tracking error. Hysteresis nonlinearity adversely affects the performance and, if not compensated, may cause inaccuracy and oscillation in the response. Compensation of hysteresis is therefore an important aspect for designing head-positioning servo system. This paper presents a new rate dependent model of hysteresis along with rigorous analysis and identification of the model. Parameters of the model are found using particle swarm optimization. Direct inverse of the proposed rate-dependent generalized Prandtl-Ishlinskii model is used as the hysteresis compensator. Effectiveness of the overall solution is underscored through experimental results.

Is mask-based stereotactic head-and-neck fixation as precise as stereotactic head fixation for precision radiotherapy?

International Nuclear Information System (INIS)

Georg, Dietmar; Bogner, Joachim; Dieckmann, Karin; Poetter, Richard

2006-01-01

Background: The aim of this study was to compare setup accuracy and reproducibility of a stereotactic head and a head-and-neck fixation system, both based on thermoplastic material. Methods and Material: Ten patients were immobilized with a head and a head-and-neck fixation system (both BrainLAB, Germany). Both mask systems were modified with a custom-made mouthpiece and a strip of thermoplastic material attached to the lower part of the mask. During the first treatment session, after positioning patients using room lasers, two orthogonal portal images were taken as reference. Later on, at least five sets of orthogonal portal images were acquired for each patient. The isocentric setup accuracy was determined by comparing field edges and anatomic landmarks and the repositioning accuracy in the mask was obtained by comparing individual anatomic landmarks with respect to the metal balls, fixed on the masks. Systematic and random deviations and resulting three-dimensional (3D) vectors were calculated. Additionally, margins were derived from the systematic and random component of the isocentric setup accuracy. Finally, inter- and intraobserver variations were analyzed. Results: The systematic variation of the isocentric setup accuracy was very similar for the two mask systems, but the random variations were slightly larger for the head-and-neck system, resulting in a 0.4-mm larger 3D vector. The repositioning variations for the head mask were smaller compared with the head-and-neck mask, resulting in smaller 3D vectors for the random (∼0.4 mm) and systematic variations (∼0.6 mm). For both mask systems, a 2-mm margin can be used in lateral and anteroposterior direction, whereas in craniocaudal direction, this margin should be extended to 2.5 mm for the head mask and to 3 mm for the head-and-neck mask. The average absolute differences between two observers were within 0.5 mm, maximum deviations around 1 mm. Conclusion: Thermoplastic mask-based stereotactic head

Assessment of occult cervical lymph node metastasis in primary squamous cell carcinoma of the head and neck by computed tomography

International Nuclear Information System (INIS)

Shakil, U.

2015-01-01

To determine the frequency of occult (node negative) cervical lymph node metastasis in primary head and neck squamous cell carcinoma, using contrast enhanced computed tomography (CT). Study Design: Cross sectional descriptive study. Place and Duration of Study: Study was conducted in Department of Radiology, Combined Military Hospital Rawalpindi. Duration of the study was 06 months i.e. from 19th February 2011 to 19th August 2011. Patients and Methods: A total of 141 cases, fulfilling the inclusion criteria, reporting to the radiology department, were included in the study after seeking written informed consent. All patients underwent contrast enhanced CT scan of the neck from base of skull to root of neck using Asteion Whole Body X-ray CT Scanner (Model TSX-021A). Images were evaluated for the presence or absence of cervical lymph node metastasis according to the cervical lymph node metastatic criteria at each level of the neck. Results: Of the 141 patients with clinically no head and neck squamous cell carcinoma, 45.4% were found to have lymph node metastases. Frequency of occult metastases in squamous cell carcinoma of oral cavity was 47.6%, oropharynx 23.5%, larynx 33.3% and hypopharynx 78.6%. Conclusion: In clinically node negative neck, the risk of lymph node metastases is significantly high in patients of head and neck squamous cell carcinoma in our population. All patients presenting with node negative neck should undergo CT scans for early detection of occult metastasis. (author)

Characterizing occipital condyle loads under high-speed head rotation.

Science.gov (United States)

Pintar, Frank A; Yoganandan, Narayan; Baisden, Jamie

2005-11-01

Because of the need to evaluate anthropomorphic test device (ATD) biofidelity under high-head angular accelerations, the purpose of the present investigation was to develop appropriate instrumentation for intact post mortem human subject (PMHS) testing, validate the instrumentation, and obtain information to characterize the response of the head-neck complex under this loading scenario. A series of rigid-arm pendulum, inertially loaded ATD tests was conducted. Head and neck ATD hydraulic piston chin pull tests were conducted. Subsequently, a series of PMHS tests was conducted to derive the response of the human head-neck under high-rate chin loading. Finally, Hybrid III and THOR-NT ATD head-neck systems were evaluated under the same scenario as the PMHS. A parametric analysis for center of gravity (CG) location and accelerometer orientation determined that even small errors (+/- 3 mm or 2 degrees), produced errors in the force and moment calculations by as much as 17 %. If the moment of inertia (MOI) term was varied by 5 %, resulting moment calculations were affected by as much as 8 %. If the 5 % error in MOI was used to compute occipital condyle moments, and results compared to upper load cell derived moments, peaks differed by as much as 24 %. The head CG and mass MOI should be directly measured for each preparation to obtain accurate results. The injury run on each specimen resulted in predominantly C1-C2 separations or partial separations. The 50(th) percentile probability of AIS=2+ neck injury using tensile force was about 2400 N; for AIS=3+ neck injury the 50(th) percentile risk was about 3180 N. When inserting extension moment as the criteria, the 50(th) percentile probability of an AIS=2+ injury was 51 Nm. The AIS=3+ extension moment at the 50(th) percentile probability was 75 Nm. The new THOR-NT ATD head-neck produced more biofidelic responses with an alternate head-neck junction design compared to the Hybrid III ATD.

Recent Advances in High-Performance Direct Methanol Fuel Cells

Science.gov (United States)

Narayanan, S. R.; Chun, W.; Valdez, T. I.; Jeffries-Nakamura, B.; Frank, H.; Surumpudi, S.; Halpert, G.; Kosek, J.; Cropley, C.; La Conti, A. B.;

Quality of life assessment in patients treated for metastatic cutaneous squamous cell carcinoma of the head and neck.

Science.gov (United States)

Wang, A Y; Palme, C E; Wang, J T; Morgan, G J; Gebski, V; Gilchrist, J; Veness, M J

2013-07-01

Treatment for metastatic cutaneous head and neck squamous cell carcinoma is usually multimodal and associated with morbidity. This study aimed to evaluate the impact of treatment on patients' quality of life. Cross-sectional survey of 42 patients (35 men, 7 women) at least 6 months after metastatic cutaneous head and neck squamous cell carcinoma treatment, using two standardised quality of life questionnaires: the Functional Assessment of Cancer Therapy - Head and Neck questionnaire and the Facial Disability Index, with statistical analysis to identify potential predictors of outcome. Female gender correlated with significantly lower Facial Disability Index physical function scores (p = 0.017). Alcohol consumption correlated with significantly better scores for Functional Assessment social well-being (p = 0.016), general total score (p = 0.041) and overall total score (p = 0.033), and for Facial Disability Index physical function (p = 0.034). Marital status, education, employment, chemotherapy, time from last treatment, parotidectomy and facial nerve sacrifice did not affect quality of life. The commonest patient complaints were dry mouth (76 per cent), altered voice quality and strength (55 per cent), and physical appearance (45 per cent). Female gender predicts worse quality of life, while alcohol consumption (versus none) predicted for better quality of life.

Orthovoltage X-rays for Postoperative Treatment of Resected Basal Cell Carcinoma in the Head and Neck Area.

Science.gov (United States)

Duinkerken, Charlotte W; Lohuis, Peter J F M; Crijns, Marianne B; Navran, Arash; Haas, Rick L M; Hamming-Vrieze, Olga; Klop, W Martin C; van den Brekel, Michiel W M; Al-Mamgani, Abrahim

Surgery is the golden standard for treating basal cell carcinomas. In case of positive tumor margins or recurrent disease, postoperative adjuvant or salvaging therapy is suggested to achieve good local control. To retrospectively report on local control and toxicity of postoperative radiotherapy by means of orthovoltage X-rays for residual or recurrent basal cell carcinoma after surgery in the head and neck area. Sixty-six surgically resected residual or recurrent basal cell carcinomas of the head and neck region were irradiated postoperatively by means of orthovoltage X-rays at the Netherlands Cancer Institute between January 2000 and February 2015. After a median follow-up duration of 30.5 months, only 5 recurrences were reported. The 5-year local control rates at 1, 3, and 5 years were 100%, 87%, and 87%, respectively. The 5-year local control rate was 92% for immediate postoperative radiotherapy of incompletely resected basal cell carcinomas, 90% for recurrences after 1 previously performed excision, and 71% for multiple recurrences, namely, a history of more than 1 excision ( P = .437). Acute toxicity healed spontaneously within 3 months. Late toxicities were mild. Radiotherapy by means of orthovoltage X-ray is an excellent alternative for re-excision in case of incompletely resected or recurrent basal cell carcinomas that are at risk of serious functional and cosmetic impairments after re-excision, with a 5-year local control rate of 87% and a low toxicity profile.

Oriented collagen fibers direct tumor cell intravasation

KAUST Repository

Han, Weijing

2016-09-24

In this work, we constructed a Collagen I-Matrigel composite extracellular matrix (ECM). The composite ECM was used to determine the influence of the local collagen fiber orientation on the collective intravasation ability of tumor cells. We found that the local fiber alignment enhanced cell-ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (∼10 mg/mL protein concentration).

Modeling and Simulation of the Direct Methanol Fuel Cell

Science.gov (United States)

Wohr, M.; Narayanan, S. R.; Halpert, G.

1996-01-01

From intro.: The direct methanol liquid feed fuel cell uses aqueous solutions of methanol as fuel and oxygen or air as the oxidant and uses an ionically conducting polymer membrane such as Nafion(sup r)117 and the electrolyte. This type of direct oxidation cell is fuel versatile and offers significant advantages in terms of simplicity of design and operation...The present study focuses on the results of a phenomenological model based on current understanding of the various processed operating in these cells.

Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

Science.gov (United States)

Feller, L; Khammissa, R A G; Kramer, B; Altini, M; Lemmer, J

2016-02-05

Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events.

Microarray analysis of serum mRNA in patients with head and neck squamous cell carcinoma at whole-genome scale

Czech Academy of Sciences Publication Activity Database

Čapková, M.; Šáchová, Jana; Strnad, Hynek; Kolář, Michal; Hroudová, Miluše; Chovanec, M.; Čada, Z.; Štefl, M.; Valach, J.; Kastner, J.; Smetana, K. Jr.; Plzák, J.

-, April 23 (2014) ISSN 2314-6141 R&D Projects: GA MZd(CZ) NT13488 Institutional support: RVO:68378050 Keywords : Microarray Analysis * Head and Neck Squamous Cell Carcinoma * whole-genome scale Subject RIV: EB - Genetics ; Molecular Biology

Outcomes after primary chemoradiotherapy for N3 (>6 cm) head and neck squamous cell carcinoma after an FDG-PET--guided neck management policy.

Science.gov (United States)

Adams, Gerard; Porceddu, Sandro V; Pryor, David I; Panizza, Benedict; Foote, Matthew; Rowan, Ann; Burmeister, Bryan

2014-08-01

The purpose of this study was to assess whether a positron emission tomography (PET)-directed policy remains appropriate for managing neck nodes (N3; >6 cm) in head and neck squamous cell carcinoma (HNSCC). All patients with N3 (>6 cm) HNSCC treated with definitive chemoradiotherapy (CRT) at our institution between 2005 and 2012 were included in the analysis. Patients underwent PET assessment before and 12 weeks after CRT. Neck dissections were performed for PET-avid residual nodal abnormalities after complete response at the primary site. Rate of isolated nodal failure (INF) was the primary outcome. Median follow-up from diagnosis for 33 patients was 30 months (range, 6-76 months). INF occurred in 2 patients (6%) with neck dissections performed in 4 cases (12%). First failure was predominantly distant metastatic (10; 30%). The rate of INF remains low when following a PET-directed neck management policy after definitive CRT for N3 (>6 cm) HNSCC. Copyright © 2013 Wiley Periodicals, Inc.

S-1 monotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck after progression on platinum-based chemotherapy

International Nuclear Information System (INIS)

Yokota, Tomoya; Onozawa, Yusuke; Boku, Narikazu

2011-01-01

Platinum compounds play pivotal roles in treatment for squamous cell carcinoma of the head and neck. The objective was to evaluate the efficacy of S-1 monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy. We retrospectively analyzed 39 consecutive patients with recurrent or metastatic squamous cell carcinoma of the head and neck who received S-1 monotherapy after failure of platinum-based chemotherapy or chemoradiotherapy at the Shizuoka Cancer Center between August 2003 and October 2010. S-1 was given orally twice daily (80 mg/m 2 /day) for 28 days followed by a 14-day rest. The median follow-up period in survivors was 31.5 months. Among 38 patients with measurable lesions, 9 (24%) showed partial response and 15 (39%) showed stable disease. The median progression-free survival was 4.9 months and the median overall survival was 13.2 months. The median progression-free survival for oropharyngeal cancer (n=7) was significantly longer than for other cancers (n=32) (14.9 vs. 4.7 months, P=0.035). The response rate in patients with a recurrence-free interval since the last platinum administration >6.0 months was significantly better than with a recurrence-free interval 6.0 months also showed a significantly better progression-free survival (6.0 vs. 2.6 months, P=0.045). The frequency of Grade 3/4 toxicities was less than 10%. S-1 monotherapy shows promising signs of efficacy and tolerability in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy in this retrospective cohort and warrants further investigation in this population. (author)

Lymph node metastases from squamous cell carcinomas of the head and neck region

International Nuclear Information System (INIS)

Bartelink, H.

1980-01-01

A retrospective and a prospective study are described concerning the results of treatment for neck node metastases. The metastases came from squamous cell carcinomas of the head and neck region. The possibility of cure by radiotherapy is considered in detail. It appeared that the results of radiotherapy depend on the site of the primary tumour and on its occasional recurrence. From a dose-effect curve and a dose-complication curve it could be estimated that the optimal dose of irradiation was 2000 rets (72 Gray in 7 weeks). (Auth.)

Directional differentiation of chicken embryonic stem cells into ...

African Journals Online (AJOL)

Jane

2011-08-01

Aug 1, 2011 ... In this study, the differentiation potential of chicken ES cells was investigated ... Key words: Chicken embryonic stem cells, in vitro, directional differentiation, .... synthesized by using the Revert Aid first strand cDNA synthesis kit.

IL-6 Inhibition With MEDI5117 Decreases The Fraction of Head and Neck Cancer Stem Cells and Prevents Tumor Recurrence

Directory of Open Access Journals (Sweden)

Kelsey A. Finkel

2016-05-01

Full Text Available Head and neck squamous cell carcinomas (HNSCC exhibit a small population of uniquely tumorigenic cancer stem cells (CSC endowed with self-renewal and multipotency. We have recently shown that IL-6 enhances the survival and tumorigenic potential of head and neck cancer stem cells (i.e. ALDHhighCD44high cells. Here, we characterized the effect of therapeutic inhibition of IL-6 with a novel humanized anti-IL-6 antibody (MEDI5117 using three low-passage patient-derived xenograft (PDX models of HNSCC. We observed that single agent MEDI5117 inhibited the growth of PDX-SCC-M1 tumors (P < .05. This PDX model was generated from a previously untreated HNSCC. In contrast, MEDI5117 was not effective at reducing overall tumor volume for PDX models representing resistant disease (PDX-SCC-M0, PDX-SCC-M11. Low dose MEDI5117 (3 mg/kg consistently decreased the fraction of cancer stem cells in PDX models of HNSCC when compared to IgG-treated controls, as follows: PDX-SCC-M0 (P < .001, PDX-SCC-M1 (P < .001, PDX-SCC-M11 (P = .04. Interestingly, high dose MEDI5117 (30 mg/kg decreased the CSC fraction in the PDX-SCC-M11 model (P = .002, but not in PDX-SCC-M0 and PDX-SCC-M1. MEDI5117 mediated a dose-dependent decrease in the number of orospheres generated by ALDHhighCD44high cells cultured in ultra-low attachment plates (P < .05, supporting an inhibitory effect on head and neck cancer stem cells. Notably, single agent MEDI5117 reduced the overall recurrence rate of PDX-SCC-M0, a PDX generated from the local recurrence of human HNSCC. Collectively, these data demonstrate that therapeutic inhibition of IL-6 with low-dose MEDI5117 decreases the fraction of cancer stem cells, and that adjuvant MEDI5117 inhibits recurrence in preclinical models of HNSCC.

Bi-directional exchange of membrane components occurs during co-culture of mesenchymal stem cells and nucleus pulposus cells.

Science.gov (United States)

Strassburg, Sandra; Hodson, Nigel W; Hill, Patrick I; Richardson, Stephen M; Hoyland, Judith A

2012-01-01

Mesenchymal stem cell (MSC)-based therapies have been proposed as novel treatments for intervertebral disc (IVD) degeneration. We have previously demonstrated that when MSCs are co-cultured with nucleus pulposus (NP) cells with direct cell-cell contact, they differentiate along the NP lineage and simultaneously stimulate the degenerate NP cell population to regain a normal (non-degenerate) phenotype, an effect which requires cell-cell communication. However, the mechanisms by which NP cells and MSCs interact in this system are currently unclear. Thus, in this study we investigated a range of potential mechanisms for exchange of cellular components or information that may direct these changes, including cell fusion, gap-junctional communication and exchange of membrane components by direct transfer or via microvesicle formation. Flow cytometry of fluorescently labeled MSCs and NP cells revealed evidence of some cell fusion and formation of gapjunctions, although at the three timepoints studied these phenomena were detectable only in a small proportion of cells. While these mechanisms may play a role in cell-cell communication, the data suggests they are not the predominant mechanism of interaction. However, flow cytometry of fluorescently dual-labeled cells showed that extensive bi-directional transfer of membrane components is operational during direct co-culture of MSCs and NP cells. Furthermore, there was also evidence for secretion and internalization of membrane-bound microvesicles by both cell types. Thus, this study highlights bi-directional intercellular transfer of membrane components as a possible mechanism of cellular communication between MSC and NP cells.

Improved Direct Methanol Fuel Cell Stack

Science.gov (United States)

Wilson, Mahlon S.; Ramsey, John C.

2005-03-08

A stack of direct methanol fuel cells exhibiting a circular footprint. A cathode and anode manifold, tie-bolt penetrations and tie-bolts are located within the circular footprint. Each fuel cell uses two graphite-based plates. One plate includes a cathode active area that is defined by serpentine channels connecting the inlet and outlet cathode manifold. The other plate includes an anode active area defined by serpentine channels connecting the inlet and outlet of the anode manifold, where the serpentine channels of the anode are orthogonal to the serpentine channels of the cathode. Located between the two plates is the fuel cell active region.

Hydroxide Self-Feeding High-Temperature Alkaline Direct Formate Fuel Cells.

Science.gov (United States)

Li, Yinshi; Sun, Xianda; Feng, Ying

2017-05-22

Conventionally, both the thermal degradation of the anion-exchange membrane and the requirement of additional hydroxide for fuel oxidation reaction hinder the development of the high-temperature alkaline direct liquid fuel cells. The present work addresses these two issues by reporting a polybenzimidazole-membrane-based direct formate fuel cell (DFFC). Theoretically, the cell voltage of the high-temperature alkaline DFFC can be as high as 1.45 V at 90 °C. It has been demonstrated that a proof-of-concept alkaline DFFC without adding additional hydroxide yields a peak power density of 20.9 mW cm -2 , an order of magnitude higher than both alkaline direct ethanol fuel cells and alkaline direct methanol fuel cells, mainly because the hydrolysis of formate provides enough OH - ions for formate oxidation reaction. It was also found that this hydroxide self-feeding high-temperature alkaline DFFC shows a stable 100 min constant-current discharge at 90 °C, proving the conceptual feasibility. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Engineering kidney cells: reprogramming and directed differentiation to renal tissues.

Science.gov (United States)

Kaminski, Michael M; Tosic, Jelena; Pichler, Roman; Arnold, Sebastian J; Lienkamp, Soeren S

2017-07-01

Growing knowledge of how cell identity is determined at the molecular level has enabled the generation of diverse tissue types, including renal cells from pluripotent or somatic cells. Recently, several in vitro protocols involving either directed differentiation or transcription-factor-based reprogramming to kidney cells have been established. Embryonic stem cells or induced pluripotent stem cells can be guided towards a kidney fate by exposing them to combinations of growth factors or small molecules. Here, renal development is recapitulated in vitro resulting in kidney cells or organoids that show striking similarities to mammalian embryonic nephrons. In addition, culture conditions are also defined that allow the expansion of renal progenitor cells in vitro. Another route towards the generation of kidney cells is direct reprogramming. Key transcription factors are used to directly impose renal cell identity on somatic cells, thus circumventing the pluripotent stage. This complementary approach to stem-cell-based differentiation has been demonstrated to generate renal tubule cells and nephron progenitors. In-vitro-generated renal cells offer new opportunities for modelling inherited and acquired renal diseases on a patient-specific genetic background. These cells represent a potential source for developing novel models for kidney diseases, drug screening and nephrotoxicity testing and might represent the first steps towards kidney cell replacement therapies. In this review, we summarize current approaches for the generation of renal cells in vitro and discuss the advantages of each approach and their potential applications.

Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity

International Nuclear Information System (INIS)

Li, Yi; Cui, Jiang-Tao

2016-01-01

Mammalian target of rapamycin (mTOR) is a therapeutic target for head and neck squamous cell carcinoma (HNSCC). Here, we evaluated the activity of AZD-2014, a potent mTOR complex 1/2 (mTORC1/2) dual inhibitor, against HNSCC cells. We showed that AZD-2014 blocked mTORC1/2 activation in established and primary human HNSCC cells, where it was anti-proliferative and pro-apoptotic. Yet, AZD-2014 was non-cytotoxic to the human oral epithelial cells with low basal mTORC1/2 activation. In an effect to identify possible AZD-2014 resistance factors, we showed that the anti-apoptosis protein Bcl-2 was upregulated in AZD-2014-resistant SQ20B HNSCC cells. Inhibition of Bcl-2 by ABT-737 (a known Bcl-2 inhibitor) or Bcl-2 shRNA dramatically potentiated AZD-2014 lethality against HNSCC cells. On the other hand, exogenous overexpression of Bcl-2 largely attenuated AZD-2014’s activity against HNSCC cells. For the in vivo studies, we showed that oral gavage of AZD-2014 suppressed SQ20B xenograft growth in severe combined immunodeficient (SCID) mice. It also significantly improved mice survival. Importantly, AZD-2014’s anti-HNSCC activity in vivo was potentiated with co-administration of ABT-737. The preclinical results of this study suggest that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. - Highlights: • AZD-2014 blocks mTORC1/2 activation in HNSCC cells. • AZD-2014 suppresses HNSCC cell proliferation. • AZD-2014 activates caspase-3 and apoptosis in HNSCC cells. • Bcl-2 is the key resistance factor of AZD-2014 in HNSCC cells. • ABT-737 sensitizes AZD-2014-induced anti-HNSCC activity in vivo.

Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity

Energy Technology Data Exchange (ETDEWEB)

Li, Yi; Cui, Jiang-Tao, E-mail: cuijingtaopaper@126.com

2016-09-02

Mammalian target of rapamycin (mTOR) is a therapeutic target for head and neck squamous cell carcinoma (HNSCC). Here, we evaluated the activity of AZD-2014, a potent mTOR complex 1/2 (mTORC1/2) dual inhibitor, against HNSCC cells. We showed that AZD-2014 blocked mTORC1/2 activation in established and primary human HNSCC cells, where it was anti-proliferative and pro-apoptotic. Yet, AZD-2014 was non-cytotoxic to the human oral epithelial cells with low basal mTORC1/2 activation. In an effect to identify possible AZD-2014 resistance factors, we showed that the anti-apoptosis protein Bcl-2 was upregulated in AZD-2014-resistant SQ20B HNSCC cells. Inhibition of Bcl-2 by ABT-737 (a known Bcl-2 inhibitor) or Bcl-2 shRNA dramatically potentiated AZD-2014 lethality against HNSCC cells. On the other hand, exogenous overexpression of Bcl-2 largely attenuated AZD-2014’s activity against HNSCC cells. For the in vivo studies, we showed that oral gavage of AZD-2014 suppressed SQ20B xenograft growth in severe combined immunodeficient (SCID) mice. It also significantly improved mice survival. Importantly, AZD-2014’s anti-HNSCC activity in vivo was potentiated with co-administration of ABT-737. The preclinical results of this study suggest that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. - Highlights: • AZD-2014 blocks mTORC1/2 activation in HNSCC cells. • AZD-2014 suppresses HNSCC cell proliferation. • AZD-2014 activates caspase-3 and apoptosis in HNSCC cells. • Bcl-2 is the key resistance factor of AZD-2014 in HNSCC cells. • ABT-737 sensitizes AZD-2014-induced anti-HNSCC activity in vivo.

Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma

Directory of Open Access Journals (Sweden)

Soares Fernando A

2011-04-01

Full Text Available Abstract Background Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+ and recurrent head and neck squamous cell carcinoma (HNSCC may increase our understanding of the complex biology of this disease. Methods Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative or tumor recurrence (recurrent or non-recurrent tumor after treatment (surgery with neck dissection followed by radiotherapy. Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category. Results The most frequent alterations were the repression of modules in negative lymph node (N0 and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed. Conclusions The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway

The effect of red-allotrope selenium nanoparticles on head and neck squamous cell viability and growth

Directory of Open Access Journals (Sweden)

Hassan CE

2016-08-01

Full Text Available Christopher E Hassan,1 Thomas J Webster1,2 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Given their low toxicity and natural presence in the human diet, selenium nanoparticles have been established as potential candidates for the treatment of numerous cancers. Red-allotrope selenium nanoparticles (rSeNPs were synthesized and characterized in this study. Head and neck squamous cell carcinoma (HNSCC and human dermal fibroblast (HDF cells were cultured and exposed to rSeNPs at concentrations ranging from 0.01 to 100 µg rSeNP/mL media for 1–3 days. The toxicity of rSeNP toward HNSCC and HDFs was analyzed. Results indicated that the particles were approximately four times as cytotoxic toward HNSCC compared to HDFs, with their respective IC50 values at 19.22 and 59.61 µg rSeNP/mL media. Using statistical analysis, an effective dosage range for killing HNSCC cells while simultaneously minimizing damage to HDFs over a 3-day incubation period was established at 20–55 µg rSeNP/mL media. Observations showed that doses of rSeNP <5 µg rSeNP/mL media resulted in cell proliferation. Transmission electron microscopy images of HNSCC and HDF cells, both treated with rSeNPs, revealed that the rSeNPs became localized in the cytoplasm near the lysosomes and mitochondria. Analysis of cell morphology showed that the rSeNPs primarily induced HNSCC apoptosis. Collectively, these results indicated that rSeNPs are a promising option for treating HNSCC without adversely affecting healthy cells and without resorting to the use of harmful chemotherapeutics. Keywords: selenium, nanotechnology, biomaterials, head and neck squamous cell carcinoma, human dermal fibroblasts, cancer 

Basal Cell Carcinoma of the Head and Neck Region: An Analysis of 171 Cases

Directory of Open Access Journals (Sweden)

Omer Sefvan Janjua

2012-01-01

Full Text Available Objective. To analyze the pattern of presentation of basal cell carcinoma (BCC and margin status for excised specimens in the head and neck region. Study Design. Retrospective cross-sectional. Duration of Study. January 2009 to December 2011. Methodology. The database of the pathology department was searched to identify records of all malignant skin tumors that underwent standard excision with margins. Out of these records, tumors with a diagnosis of BCC in the head and neck region were retrieved and separated. Age, gender, anatomic location, pattern of tumor, and margin status were noted. Results. A total of 171 cases of BCC from various sites of head and neck were retrieved. Male to female ratio was 1.4 : 1. The age ranged from 22 to 90 years. Seventy-six cases presented on right side, 79 on left, and 16 were in the midline. Most common anatomical site was the nose followed by the cheek. Nodular lesions were the most common (46.2% followed by pigmented variety (18.7%. Margins were clear in 77 (45.1% cases, involved in 86 (50.2% cases, and close in 8 (4.7% cases. Conclusion. Nose was the most common site followed by the cheek. Nodular and pigmented varieties were the most frequent and margins were involved in more than fifty percent of the cases.

Basal Cell Carcinoma of the Head and Neck Region: An Analysis of 171 Cases

International Nuclear Information System (INIS)

Janjua, O. S.; Qureshi, S. M.

2012-01-01

Objective. To analyze the pattern of presentation of basal cell carcinoma (BCC) and margin status for excised specimens in the head and neck region. Study Design. Retrospective cross-sectional. Duration of Study. January 2009 to December 2011. Methodology. The database of the pathology department was searched to identify records of all malignant skin tumors that underwent standard excision with margins. Out of these records, tumors with a diagnosis of BCC in the head and neck region were retrieved and separated. Age, gender, anatomic location, pattern of tumor, and margin status were noted. Results. A total of 171 cases of BCC from various sites of head and neck were retrieved. Male to female ratio was 1.4?:?1. The age ranged from 22 to 90 years. Seventy-six cases presented on right side, 79 on left, and 16 were in the midline. Most common anatomical site was the nose followed by the cheek. Nodular lesions were the most common (46.2%) followed by pigmented variety (18.7%). Margins were clear in 77 (45.1%) cases, involved in 86 (50.2%) cases, and close in 8 (4.7%) cases. Conclusion. Nose was the most common site followed by the cheek. Nodular and pigmented varieties were the most frequent and margins were involved in more than fifty percent of the cases

Elevated expression of MMP-13 and TIMP-1 in head and neck squamous cell carcinomas may reflect increased tumor invasiveness

International Nuclear Information System (INIS)

Culhaci, Nil; Metin, Kubilay; Copcu, Eray; Dikicioglu, Emel

2004-01-01

Matrix metalloproteinases [MMPs], which degrade the extracellular matrix, play an important role in the invasion and metastasis of squamous cell carcinomas. One MMP, MMP-13, is thought to play a central role in MMP activation. The purpose of this study was to investigate MMP-13 and TIMP-1 expression in squamous cell carcinomas of the head and neck and to relate these levels of expression to histologic patterns of invasion. This study included T1 lesions obtained via biopsy from the larynx, tongue, and skin/mucosa of 78 patients with head and neck squamous cell carcinomas. The relationship between expression of MMP-13 and TIMP-1 and the mode of tumor invasion [MI] was evaluated immunohistochemically, using breast carcinoma tissue as a positive control. Increased expression was observed in highly invasive tumors, as reflected by the significant correlation between the degree of staining for MMP-13 or TIMP-1 and MI grade [p < 0.05]. There was no significant relationship between the degree of staining for MMP-13 or TIMP-1 and patient age, sex, tumor site, or tumor histologic grade. In addition, levels of staining for MMP-13 did not correlate with levels of staining for TIMP-1. The expression of MMP-13 and TIMP-1 appears to play an important role in determining the invasive capacity of squamous cell carcinomas of the head and neck. Whereas additional studies are needed to confirm these findings, evaluating expression of these MMPs in small biopsy samples may be useful in determining the invasive capacity of these tumors at an earlier stage

Directed neuronal differentiation of human embryonic stem cells

Directory of Open Access Journals (Sweden)

Noggle Scott A

2003-10-01

Full Text Available Abstract Background We have developed a culture system for the efficient and directed differentiation of human embryonic stem cells (HESCs to neural precursors and neurons. HESC were maintained by manual passaging and were differentiated to a morphologically distinct OCT-4+/SSEA-4- monolayer cell type prior to the derivation of embryoid bodies. Embryoid bodies were grown in suspension in serum free conditions, in the presence of 50% conditioned medium from the human hepatocarcinoma cell line HepG2 (MedII. Results A neural precursor population was observed within HESC derived serum free embryoid bodies cultured in MedII conditioned medium, around 7–10 days after derivation. The neural precursors were organized into rosettes comprised of a central cavity surrounded by ring of cells, 4 to 8 cells in width. The central cells within rosettes were proliferating, as indicated by the presence of condensed mitotic chromosomes and by phosphoHistone H3 immunostaining. When plated and maintained in adherent culture, the rosettes of neural precursors were surrounded by large interwoven networks of neurites. Immunostaining demonstrated the expression of nestin in rosettes and associated non-neuronal cell types, and a radial expression of Map-2 in rosettes. Differentiated neurons expressed the markers Map-2 and Neurofilament H, and a subpopulation of the neurons expressed tyrosine hydroxylase, a marker for dopaminergic neurons. Conclusion This novel directed differentiation approach led to the efficient derivation of neuronal cultures from HESCs, including the differentiation of tyrosine hydroxylase expressing neurons. HESC were morphologically differentiated to a monolayer OCT-4+ cell type, which was used to derive embryoid bodies directly into serum free conditions. Exposure to the MedII conditioned medium enhanced the derivation of neural precursors, the first example of the effect of this conditioned medium on HESC.

Heading and head injuries in soccer.

Science.gov (United States)

Kirkendall, D T; Jordan, S E; Garrett, W E

2001-01-01

In the world of sports, soccer is unique because of the purposeful use of the unprotected head for controlling and advancing the ball. This skill obviously places the player at risk of head injury and the game does carry some risk. Head injury can be a result of contact of the head with another head (or other body parts), ground, goal post, other unknown objects or even the ball. Such impacts can lead to contusions, fractures, eye injuries, concussions or even, in rare cases, death. Coaches, players, parents and physicians are rightly concerned about the risk of head injury in soccer. Current research shows that selected soccer players have some degree of cognitive dysfunction. It is important to determine the reasons behind such deficits. Purposeful heading has been blamed, but a closer look at the studies that focus on heading has revealed methodological concerns that question the validity of blaming purposeful heading of the ball. The player's history and age (did they play when the ball was leather and could absorb significant amounts of water), alcohol intake, drug intake, learning disabilities, concussion definition and control group use/composition are all factors that cloud the ability to blame purposeful heading. What does seem clear is that a player's history of concussive episodes is a more likely explanation for cognitive deficits. While it is likely that the subconcussive impact of purposeful heading is a doubtful factor in the noted deficits, it is unknown whether multiple subconcussive impacts might have some lingering effects. In addition, it is unknown whether the noted deficits have any affect on daily life. Proper instruction in the technique is critical because if the ball contacts an unprepared head (as in accidental head-ball contacts), the potential for serious injury is possible. To further our understanding of the relationship of heading, head injury and cognitive deficits, we need to: learn more about the actual impact of a ball on the

Evidence for Acute Electrophysiological and Cognitive Changes Following Routine Soccer Heading

Directory of Open Access Journals (Sweden)

Thomas G. Di Virgilio

2016-11-01

Discussion: Sub-concussive head impacts routine in soccer heading are associated with immediate, measurable electrophysiological and cognitive impairments. Although these changes in brain function were transient, these effects may signal direct consequences of routine soccer heading on (long-term brain health which requires further study.

Merkel Cell Carcinoma of the Head and Neck: A Single Institutional Experience

International Nuclear Information System (INIS)

Morand, G.; Vital, D.; Pezier, T.; Holzmann, D.; Huber, G.F.; Roessle, M.; Cozzio, A.

2013-01-01

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy occurring mostly in older immunocompromised Caucasian males. A growing incidence of MCC has been reported in epidemiological studies. Treatment of MCC usually consists of surgical excision, pathological lymph node evaluation, and adjuvant radiotherapy. This paper reports the experience of a single tertiary center institution with 17 head and neck Merkel cell carcinoma patients. Median followup for the cohort was 37.5 months. After five years, recurrence-free survival, disease specific survival, and overall survival were 85%, 90%, and 83%, respectively. Our limited data support the use of adjuvant radiotherapy. We also report two cases of MCC located at the vestibule of the nose and two cases of spontaneous regression after diagnostic biopsy. About 40% of our patients were referred to our center for surgical revision and pathological lymph node evaluation. Increased awareness of MCC and an interdisciplinary approach are essential in the management of MCC.

Axis of eye rotation changes with head-pitch orientation during head impulses about earth-vertical.

Science.gov (United States)

Migliaccio, Americo A; Schubert, Michael C; Clendaniel, Richard A; Carey, John P; Della Santina, Charles C; Minor, Lloyd B; Zee, David S

2006-06-01

The goal of this study was to assess how the axis of head rotation, Listing's law, and eye position influence the axis of eye rotation during brief, rapid head rotations. We specifically asked how the axis of eye rotation during the initial angular vestibuloocular reflex (VOR) changed when the pitch orientation of the head relative to Earth-vertical was varied, but the initial position of the eye in the orbit and the orientation of Listing's plane with respect to the head were fixed. We measured three-dimensional eye and head rotation axes in eight normal humans using the search coil technique during head-and-trunk (whole-body) and head-on-trunk (head-only) "impulses" about an Earth-vertical axis. The head was initially oriented at one of five pitch angles (30 degrees nose down, 15 degrees nose down, 0 degrees, 15 degrees nose up, 30 degrees nose up). The fixation target was always aligned with the nasooccipital axis. Whole-body impulses were passive, unpredictable, manual, rotations with peak-amplitude of approximately 20 degrees , peak-velocity of approximately 80 degrees /s, and peak-acceleration of approximately 1000 degrees /s2. Head-only impulses were also passive, unpredictable, manual, rotations with peak-amplitude of approximately 20 degrees , peak-velocity of approximately 150 degrees /s, and peak-acceleration of approximately 3000 degrees /s2. During whole-body impulses, the axis of eye rotation tilted in the same direction, and by an amount proportional (0.51 +/- 0.09), to the starting pitch head orientation (P rotation could be predicted from vectorial summation of the gains (eye velocity/head velocity) obtained for rotations about the pure yaw and roll head axes. Thus, even when the orientation of Listing's plane and eye position in the orbit are fixed, the axis of eye rotation during the VOR reflects a compromise between the requirements of Listing's law and a perfectly compensatory VOR.

3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226

International Nuclear Information System (INIS)

Hehlgans, Stephanie; Lange, Inga; Eke, Iris; Cordes, Nils

2009-01-01

Background and purpose: Focal adhesion kinase (FAK), a main player in integrin signaling and survival, is frequently overexpressed in human cancers and therefore postulated as potential target in cancer therapy. The aim of this study was to evaluate the radiosensitizing potential of the FAK inhibitor TAE226 in three-dimensional (3D) tumor cell cultures. Materials and methods: Head and neck squamous cell carcinoma (HNSCC) cells (FaDu, UT-SCC15, UT-SCC45), lung cancer cells (A549), colorectal carcinoma cells (DLD-1, HCT-116) and pancreatic tumor cells (MiaPaCa2, Panc1) were treated with different concentrations of TAE226 (0-1 μm; 1 or 24 h) without or in combination with irradiation (0-6 Gy, X-ray, single dose). Subsequently, 3D clonogenic survival assays (laminin-rich extracellular matrix) and Western blotting (expression/phosphorylation, e.g. FAK, Akt, ERK1/2) were performed. Results: All investigated 3D cell cultures showed a dose-dependent reduction in clonogenic survival by TAE226. Intriguingly, TAE226 only significantly radiosensitized 3D HNSCC cell cultures accompanied by a pronounced dephosphorylation of FAK, Akt and ERK1/2. Conclusions: Our data demonstrate TAE226 as potent FAK inhibitor that enhances the cellular radiosensitivity particularly of HNSCC cells grown in a 3D cell culture model. Future in vitro and in vivo investigations will clarify, to which extent this approach might be clinically relevant for radiotherapy of HNSCC.

Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells

Directory of Open Access Journals (Sweden)

Yu-Chin Lin

2012-06-01

Full Text Available Epidermal growth factor receptor (EGFR is an important oncoprotein that promotes cell growth and proliferation. Dasatinib, a bcr-abl inhibitor, has been approved clinically for the treatment of chronic myeloid leukemia and demonstrated to be effective against solid tumors in vitro through Src inhibition. Here, we disclose that EGFR degradation mediated dasatinib-induced apoptosis in head and neck squamous cell carcinoma (HNSCC cells. HNSCC cells, including Ca9-22, FaDu, HSC3, SAS, SCC-25, and UMSCC1, were treated with dasatinib, and cell viability, apoptosis, and underlying signal transduction were evaluated. Dasatinib exhibited differential sensitivities against HNSCC cells. Growth inhibition and apoptosis were correlated with its inhibition on Akt, Erk, and Bcl-2, irrespective of Src inhibition. Accordingly, we found that down-regulation of EGFR was a determinant of dasatinib sensitivity. Lysosome inhibitor reversed dasatinib-induced EGFR down-regulation, and c-cbl activity was increased by dasatinib, indicating that dasatinib-induced EGFR down-regulation might be through c-cbl-mediated lysosome degradation. Increased EGFR activation by ligand administration rescued cells from dasatinib-induced apoptosis, whereas inhibition of EGFR enhanced its apoptotic effect. Estrogen receptor α (ERα was demonstrated to play a role in Bcl-2 expression, and dasatinib inhibited ERα at the pretranslational level. ERα was associated with EGFR in dasatinib-treated HNSCC cells. Furthermore, the xenograft model showed that dasatinib inhibited HSC3 tumor growth through in vivo down-regulation of EGFR and ERα. In conclusion, degradation of EGFR is a novel mechanism responsible for dasatinib-induced apoptosis in HNSCC cells.

Public knowledge of head and neck cancer.

LENUS (Irish Health Repository)

O'Connor, T E

2010-04-01

Studies show 60% of patients with newly diagnosed Head & Neck Squamous Cell Cancer in Ireland, present with advanced disease. A poor level of knowledge and awareness among the public of Head & Neck Cancer, is an important consideration in the often delayed presentation for medical attention in many of these cases. Our study surveyed 200 members of the public to assess their knowledge and awareness of Head & Neck Cancer. One hundred and forty (70%) of respondents had never encountered the term "Head & Neck Cancer". One hundred and forty six (73%) failed to identify excessive alcohol consumption as a risk factor. Less than 100 (50%) would have concern about persisting hoarseness or a prolonged oral ulcer. An urgent need exists to raise awareness of Head & Neck Cancer among the public in Ireland.

Schwannomas of the head and neck

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Anastasios Kanatas

2011-12-01

Full Text Available Schwannomas are benign encapsulated nerve sheath tumors composed of Schwann cells. Malignant change in head and neck schwannomas is rare, with the incidence varying between 8 and 13.9%. In this review, we discuss the presentation and the management of head and neck schwannomas. The issues and difficulties based on our own experience as well as the experience of published reports from the literature are presented.

Oncogenic impact of human papilloma virus in head and neck cancer.

LENUS (Irish Health Repository)

Heffernan, C B

2012-02-01

There is considerable debate within the literature about the significance of human papilloma virus in head and neck squamous cell carcinoma, and its potential influence on the prevention, diagnosis, grading, treatment and prognosis of these cancers. Cigarette smoking and alcohol consumption have traditionally been cited as the main risk factors for head and neck cancers. However, human papilloma virus, normally associated with cervical and other genital carcinomas, has emerged as a possible key aetiological factor in head and neck squamous cell carcinoma, especially oropharyngeal cancers. These cancers pose a significant financial burden on health resources and are increasing in incidence. The recent introduction of vaccines targeted against human papilloma virus types 16 and 18, to prevent cervical cancer, has highlighted the need for ongoing research into the importance of human papilloma virus in head and neck squamous cell carcinoma.

Complex p63 mRNA isoform expression patterns in squamous cell carcinoma of the head and neck

DEFF Research Database (Denmark)

Thurfjell, N.; Coates, P.J.; Uusitalo, T.

2004-01-01

on the role of p63 expression in human tumours, we used quantitative real-time RT-PCR to study individual p63 isoforms in squamous cell carcinomas of the head and neck (SCCHN). In keeping with previous reports, expression of the deltaN- and p63alpha-isoforms predominated and deltaNp63 mRNA was expressed...

Macroscopic Modeling of Transport Phenomena in Direct Methanol Fuel Cells

DEFF Research Database (Denmark)

Olesen, Anders Christian

An increasing need for energy efficiency and high energy density has sparked a growing interest in direct methanol fuel cells for portable power applications. This type of fuel cell directly generates electricity from a fuel mixture consisting of methanol and water. Although this technology...... surpasses batteries in important areas, fundamental research is still required to improve durability and performance. Particularly the transport of methanol and water within the cell structure is difficult to study in-situ. A demand therefore exist for the fundamental development of mathematical models...... for studying their transport. In this PhD dissertation the macroscopic transport phenomena governing direct methanol fuel cell operation are analyzed, discussed and modeled using the two-fluid approach in the computational fluid dynamics framework of CFX 14. The overall objective of this work is to extend...

Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis

International Nuclear Information System (INIS)

Arenz, Andrea; Ziemann, Frank; Wittig, Andrea; Preising, Stefanie; Engenhart-Cabillic, Rita; Mayer, Christina; Wagner, Steffen; Klussmann, Jens-Peter; Wittekindt, Claus; Dreffke, Kirstin

2014-01-01

Human Papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) respond favourably to radiotherapy as compared to HPV-unrelated HNSCC. We investigated DNA damage response in HPV-positive and HPV-negative HNSCC cell lines aiming to identify mechanisms, which illustrate reasons for the increased sensitivity of HPV-positive cancers of the oropharynx. Radiation response including clonogenic survival, apoptosis, DNA double-strand break (DSB) repair, and cell cycle redistribution in four HPV-positive (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) and four HPV-negative (UD-SCC-1, UM-SCC-6, UM-SCC-11b, UT-SCC-33) cell lines was evaluated. HPV-positive cells were more radiosensitive (mean SF2: 0.198 range: 0.22-0.18) than HPV-negative cells (mean SF2: 0.34, range: 0.45-0.27; p = 0.010). Irradiated HPV-positive cell lines progressed faster through S-phase showing a more distinct accumulation in G2/M. The abnormal cell cycle checkpoint activation was accompanied by a more pronounced increase of cell death after x-irradiation and a higher number of residual and unreleased DSBs. The enhanced responsiveness of HPV-related HNSCC to radiotherapy might be caused by a higher cellular radiosensitivity due to cell cycle dysregulation and impaired DNA DSB repair. (orig.) [de

Extending EV Range with Direct Methanol Fuel Cells

OpenAIRE

Steckmann, Kai

2009-01-01

Electric cars are the vehicles of the future, and there is a proven hybrid system for extending their mileage. Direct methanol fuel cells (DMFCs) provide safe, lightweight, onboard battery charging that can free car owners from worry about running out of power. The hybrid system includes a DMFC fuel cell, fuel cell cartridge and electric vehicle batteries. The fuel cell operates almost silently with virtually no exhaust, it is immune to extreme weather and the convenient fuel cartridges featu...

Direct-write Bioprinting of Cell-laden Methacrylated Gelatin Hydrogels

Science.gov (United States)

Bertassoni, Luiz E.; Cardoso, Juliana C.; Manoharan, Vijayan; Cristino, Ana L.; Bhise, Nupura S.; Araujo, Wesleyan A.; Zorlutuna, Pinar; Vrana, Nihal E.; Ghaemmaghami, Amir M.

2014-01-01

Fabrication of three dimensional (3D) organoids with controlled microarchitectures has been shown to enhance tissue functionality. Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture. Therefore, it represents an exciting alternative for organ fabrication. Despite the rapid progress in the field, the development of printing processes that can be used to fabricate macroscale tissue constructs from ECM-derived hydrogels has remained a challenge. Here we report a strategy for bioprinting of photolabile cell-laden methacrylated gelatin (GelMA) hydrogels. We bioprinted cell-laden GelMA at concentrations ranging from 7 to 15% with varying cell densities and found a direct correlation between printability and the hydrogel mechanical properties. Furthermore, encapsulated HepG2 cells preserved cell viability for at least 8 days following the bioprinting process. In summary, this work presents a strategy for direct-write bioprinting of a cell-laden photolabile ECM-derived hydrogel, which may find widespread application for tissue engineering, organ printing and the development of 3D drug discovery platforms. PMID:24695367

Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels

International Nuclear Information System (INIS)

Bertassoni, Luiz E; Cardoso, Juliana C; Manoharan, Vijayan; Cristino, Ana L; Bhise, Nupura S; Araujo, Wesleyan A; Zorlutuna, Pinar; Vrana, Nihal E; Dokmeci, Mehmet R; Khademhosseini, Ali; Ghaemmaghami, Amir M

2014-01-01

Fabrication of three dimensional (3D) organoids with controlled microarchitectures has been shown to enhance tissue functionality. Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture. Therefore, it represents an exciting alternative for organ fabrication. Despite the rapid progress in the field, the development of printing processes that can be used to fabricate macroscale tissue constructs from ECM-derived hydrogels has remained a challenge. Here we report a strategy for bioprinting of photolabile cell-laden methacrylated gelatin (GelMA) hydrogels. We bioprinted cell-laden GelMA at concentrations ranging from 7 to 15% with varying cell densities and found a direct correlation between printability and the hydrogel mechanical properties. Furthermore, encapsulated HepG2 cells preserved cell viability for at least eight days following the bioprinting process. In summary, this work presents a strategy for direct-write bioprinting of a cell-laden photolabile ECM-derived hydrogel, which may find widespread application for tissue engineering, organ printing and the development of 3D drug discovery platforms. (paper)

Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels.

Science.gov (United States)

Bertassoni, Luiz E; Cardoso, Juliana C; Manoharan, Vijayan; Cristino, Ana L; Bhise, Nupura S; Araujo, Wesleyan A; Zorlutuna, Pinar; Vrana, Nihal E; Ghaemmaghami, Amir M; Dokmeci, Mehmet R; Khademhosseini, Ali

2014-06-01

Fabrication of three dimensional (3D) organoids with controlled microarchitectures has been shown to enhance tissue functionality. Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture. Therefore, it represents an exciting alternative for organ fabrication. Despite the rapid progress in the field, the development of printing processes that can be used to fabricate macroscale tissue constructs from ECM-derived hydrogels has remained a challenge. Here we report a strategy for bioprinting of photolabile cell-laden methacrylated gelatin (GelMA) hydrogels. We bioprinted cell-laden GelMA at concentrations ranging from 7 to 15% with varying cell densities and found a direct correlation between printability and the hydrogel mechanical properties. Furthermore, encapsulated HepG2 cells preserved cell viability for at least eight days following the bioprinting process. In summary, this work presents a strategy for direct-write bioprinting of a cell-laden photolabile ECM-derived hydrogel, which may find widespread application for tissue engineering, organ printing and the development of 3D drug discovery platforms.

[Planned neck dissection in the treatment of locally advanced head and neck squamous cell carcinoma].

Science.gov (United States)

Jiang, L; Lou, J L; Wang, K J; Fang, M Y; Fu, Z F

2018-02-07

Objective: To investigate the value of planned neck dissection combined with induction chemotherapy and concurrent chemoradiotherapy in regional control and the outcome of locally advanced head and neck squamous cell carcinoma. Methods: A prospective randomized controlled study totally enrolled sixty-four patients of head and neck squamous cell carcinomas(include oropharynx, hypopharynx, and larynx) in stages Ⅳa-Ⅳb with lymph node metastase was were N2-N3. All patients firstly received 2-3 cycles of induction chemotherapy(ICT), then divided into two groups randomly, according to the efficacy of ICT. Group A(the study group) received planned neck dissection(PND) and concurrent chemoradiotherapy(CCRT). Group B(the control group) received concurrent chemoradiotherapy(CCRT). The differences in clinicopathologic features, local recurrence(LR), regional recurrence(RR), disease-free survival(DFS), and overall survival(OS) between the two groups were estimated. SPSS 19.0 software was used to analyze the data. Results: Group A enrolled twenty-one patients, and group B enrolled forty-three patients.The follow-up of all patients were 4-55 months, median follow-up time was 22 months. In study group, two-year OS and DFS were 80.9% and 68.3%, respectively. In control group, two-year OS and DFS were 90.7% and 67.1%, respectively. There was no significant difference in gender( P =0.215), age( P =0.828), primary tumor site( P =0.927), LR( P =0.126), DFS( P =0.710), and OS( P =0.402) between the two groups, while the RR(χ(2)=5.640, P squamous cell carcinoma.

Simplified realistic human head model for simulating Tumor Treating Fields (TTFields).

Science.gov (United States)

Wenger, Cornelia; Bomzon, Ze'ev; Salvador, Ricardo; Basser, Peter J; Miranda, Pedro C

2016-08-01

Tumor Treating Fields (TTFields) are alternating electric fields in the intermediate frequency range (100-300 kHz) of low-intensity (1-3 V/cm). TTFields are an anti-mitotic treatment against solid tumors, which are approved for Glioblastoma Multiforme (GBM) patients. These electric fields are induced non-invasively by transducer arrays placed directly on the patient's scalp. Cell culture experiments showed that treatment efficacy is dependent on the induced field intensity. In clinical practice, a software called NovoTalTM uses head measurements to estimate the optimal array placement to maximize the electric field delivery to the tumor. Computational studies predict an increase in the tumor's electric field strength when adapting transducer arrays to its location. Ideally, a personalized head model could be created for each patient, to calculate the electric field distribution for the specific situation. Thus, the optimal transducer layout could be inferred from field calculation rather than distance measurements. Nonetheless, creating realistic head models of patients is time-consuming and often needs user interaction, because automated image segmentation is prone to failure. This study presents a first approach to creating simplified head models consisting of convex hulls of the tissue layers. The model is able to account for anisotropic conductivity in the cortical tissues by using a tensor representation estimated from Diffusion Tensor Imaging. The induced electric field distribution is compared in the simplified and realistic head models. The average field intensities in the brain and tumor are generally slightly higher in the realistic head model, with a maximal ratio of 114% for a simplified model with reasonable layer thicknesses. Thus, the present pipeline is a fast and efficient means towards personalized head models with less complexity involved in characterizing tissue interfaces, while enabling accurate predictions of electric field distribution.

Direct Head-To-Head Comparison of Cationic Liposome-Mediated Gene Delivery to Mesenchymal Stem/Stromal Cells of Different Human Sources: A Comprehensive Study

Science.gov (United States)

Boura, Joana S.; dos Santos, Francisco; Gimble, Jeffrey M.; Cardoso, Carla M.P.; Madeira, Catarina; Cabral, Joaquim M.S.

2013-01-01

Abstract Nonviral gene delivery to human mesenchymal stem/stromal cells (MSC) can be considered a very promising strategy to improve their intrinsic features, amplifying the therapeutic potential of these cells for clinical applications. In this work, we performed a comprehensive comparison of liposome-mediated gene transfer efficiencies to MSC derived from different human sources—bone marrow (BM MSC), adipose tissue-derived cells (ASC), and umbilical cord matrix (UCM MSC). The results obtained using a green fluorescent protein (GFP)-encoding plasmid indicated that MSC isolated from BM and UCM are more amenable to genetic modification when compared to ASC as they exhibited superior levels of viable, GFP+ cells 48 hr post-transfection, 58±7.1% and 54±3.8%, respectively, versus 33±4.7%. For all cell sources, high cell recoveries (≈50%) and viabilities (>85%) were achieved, and the transgene expression was maintained for 10 days. Levels of plasmid DNA uptake, as well as kinetics of transgene expression and cellular division, were also determined. Importantly, modified cells were found to retain their characteristic immunophenotypic profile and multilineage differentiation capacity. By using the lipofection protocol optimized herein, we were able to maximize transfection efficiencies to human MSC (maximum of 74% total GFP+ cells) and show that lipofection is a promising transfection strategy for MSC genetic modification, especially when a transient expression of a therapeutic gene is required. Importantly, we also clearly demonstrated that intrinsic features of MSC from different sources should be taken into consideration when developing and optimizing strategies for MSC engineering with a therapeutic gene. PMID:23360350

Recurrent copy number gains of ACVR1 and corresponding transcript overexpression are associated with survival in head and neck squamous cell carcinomas

DEFF Research Database (Denmark)

Ambrosio, Eliane P; Drigo, Sandra A; Bérgamo, Nádia A

2011-01-01

AIMS: This study aimed to evaluate the copy number alteration on 2q24, its association with ACVR1 transcript expression and the prognostic value of these data in head and neck squamous cell carcinomas. METHODS AND RESULTS: Twenty-eight samples of squamous cell carcinoma were evaluated by fluoresc...

Porous silicon-based direct hydrogen sulphide fuel cells.

Science.gov (United States)

Dzhafarov, T D; Yuksel, S Aydin

2011-10-01

In this paper, the use of Au/porous silicon/Silicon Schottky type structure, as a direct hydrogen sulphide fuel cell is demonstrated. The porous silicon filled with hydrochlorid acid was developed as a proton conduction membrane. The Au/Porous Silicon/Silicon cells were fabricated by first creating the porous silicon layer in single-crystalline Si using the anodic etching under illumination and then deposition Au catalyst layer onto the porous silicon. Using 80 mM H2S solution as fuel the open circuit voltage of 0.4 V was obtained and maximum power density of 30 W/m2 at room temperature was achieved. These results demonstrate that the Au/Porous Silicon/Silicon direct hydrogen sulphide fuel cell which uses H2S:dH2O solution as fuel and operates at room temperature can be considered as the most promising type of low cost fuel cell for small power-supply units.

Directional Cell Migration in Response to Repeated Substratum Stretching

Science.gov (United States)

Okimura, Chika; Iwadate, Yoshiaki

2017-10-01

Crawling migration plays an essential role in a variety of biological phenomena, including development, wound healing, and immune system function. Migration properties such as anterior-posterior polarity, directionality, and velocity are regulated not only by the reception of a chemoattractant but also by sensing mechanical inputs from the external environment. In this review, we describe the mechanical response of migrating cells, particularly under repeated stretching of the elastic substratum, highlighting the fact that there appear to be two independent mechanosensing systems that generate the polarity needed for migration. Cells that have no stress fibers, such as Dictyostelium cells and neutrophil-like differentiated HL-60 cells, migrate perpendicular to the stretching direction via myosin II localization. Cells that do possess stress fibers, however, such as fish keratocytes, migrate parallel to the stretching via a stress-fiber-dependent process.

A novel direct carbon fuel cell by approach of tubular solid oxide fuel cells

Energy Technology Data Exchange (ETDEWEB)

Liu, Renzhu; Zhao, Chunhua; Li, Junliang; Zeng, Fanrong; Wang, Shaorong; Wen, Tinglian; Wen, Zhaoyin [CAS Key Laboratory of Materials for Energy Conversion, Shanghai Inorganic Energy Materials and Power Source Engineering Center, Shanghai Institute of Ceramics, Chinese Academy of Sciences (SICCAS), 1295 Dingxi Road, Shanghai 200050 (China)

2010-01-15

A direct carbon fuel cell based on a conventional anode-supported tubular solid oxide fuel cell, which consisted of a NiO-YSZ anode support tube, a NiO-ScSZ anode functional layer, a ScSZ electrolyte film, and a LSM-ScSZ cathode, has been successfully achieved. It used the carbon black as fuel and oxygen as the oxidant, and a preliminary examination of the DCFC has been carried out. The cell generated an acceptable performance with the maximum power densities of 104, 75, and 47 mW cm{sup -2} at 850, 800, and 750 C, respectively. These results demonstrate the feasibility for carbon directly converting to electricity in tubular solid oxide fuel cells. (author)

A Direct DME High Temperature PEM Fuel Cell

DEFF Research Database (Denmark)

Vassiliev, Anton; Jensen, Jens Oluf; Li, Qingfeng

2012-01-01

Dimethyl ether (DME) has been identified as an alternative to methanol for use in direct fuel cells. It combines the advantages of hydrogen in terms of pumpless fuel delivery and high energy density like methanol, but without the toxicity of the latter. The performance of a direct dimethyl ether...... fuel cell suffers greatly from the very low DME-water miscibility. To cope with the problem polybenzimidazole (PBI) based membrane electrode assemblies (MEAs) have been made and tested in a vapor fed system. PtRu on carbon has been used as anode catalyst and air at ambient pressure was used as oxidant...

Unilateral otolith centrifugation by head tilt.

Science.gov (United States)

Winters, Stephanie M; Bos, Jelte E; Klis, Sjaak F L

2014-01-01

To test for otolith asymmetries, several studies described horizontal translation of the body and head en bloc during fast vertical axis rotation. This stimulus causes one otolithic organ to rotate on-axis, and the other to experience centripetal acceleration. To test a new, more simple method of unilateral stimulation with head tilt and the body remaining on axis. During stationary and during 360 deg/s rotation, 12 healthy blindfolded subjects had their heads tilted 30 degrees sideways, positioning one otolithic organ on the axis of rotation after the other. The haptic subjective vertical (SV) was recorded several times by means of a manually adjustable rod. It was found that during stationary the SV tilted about 4 degrees on average in the direction of the head. During rotation, the SV tilted about 9 degrees on average. We therefore estimate the effect of eccentric otolith rotation to be 5 degrees on average. Tilt of the subjective vertical induced by head tilt during on-axis body rotation can provide a relatively uncomplicated alternative to test unilateral otolithic function as compared to body and head translation during rotation. Moreover, unlike eccentric rotation of the entire body, somatosensory cues are minimized by keeping the body fixed on axis and by subtracting the effect of head tilt per se.

Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.

Science.gov (United States)

Arosarena, Oneida A; Barr, Eric W; Thorpe, Ryan; Yankey, Hilary; Tarr, Joseph T; Safadi, Fayez F

2018-01-01

Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP-10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP-9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP-10 expression in UMSCC12 cells (p = 0.0001), and MMP-3 (p = 0.0005) and -9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP-2 (p = 0.0408) and MMP-9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP-2 (p = 0.0023) and -9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion. © 2017 Wiley Periodicals, Inc.

Phase II study of 3-AP Triapine in patients with recurrent or metastatic head and neck squamous cell carcinoma.

NARCIS (Netherlands)

Nutting, C.M.; Herpen, C.M.L. van; Miah, A.B.; Bhide, S.A.; Machiels, J.P.; Buter, J.; Kelly, C.; Raucourt, D. de; Harrington, K.J.

2009-01-01

BACKGROUND: Treatment options for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are limited with response rates to cytotoxic chemotherapy of approximately 30% and median survival of 6 months. PATIENTS AND METHODS: In a multicentre phase II study, 32 patients with recurrent or

Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial

DEFF Research Database (Denmark)

Alkureishi, Lee W T; Ross, Gary L; Shoaib, Taimur

2010-01-01

Sentinel node biopsy (SNB) may represent an alternative to elective neck dissection for the staging of patients with early head and neck squamous cell carcinoma (HNSCC). To date, the technique has been successfully described in a number of small single-institution studies. This report describes...

Increase of bcl-2 Protein Expression in Aggressive Basal Cell Carcinoma of Head and Neck

OpenAIRE

Cláudia CAZAL; Mariana Roesch ELY; Ana Paula Veras SOBRAL; Wilton Wilney Nascimento PADILHA

2006-01-01

Objective: The aim of this study was to verify the bcl-2 protein expression in 22 cutaneous basal cell carcinomas (BCC) of the head and neck, and to compare it with its aggressive behavior. Method: Tumors were histologically classified in non-aggressive (BCC 1) and aggressive (BCC 2) and then submitted to the immunohistochemistry technique with the streptavidin-biotin peroxidase method using the anti-bcl-2 antibody. Results: After proceeding to morphological analysis, sixteen tumors (72.7%) w...

Head position modulates optokinetic nystagmus.

Science.gov (United States)

Pettorossi, V E; Ferraresi, A; Botti, F M; Panichi, R; Barmack, N H

2011-08-01

Orientation and movement relies on both visual and vestibular information mapped in separate coordinate systems. Here, we examine how coordinate systems interact to guide eye movements of rabbits. We exposed rabbits to continuous horizontal optokinetic stimulation (HOKS) at 5°/s to evoke horizontal eye movements, while they were statically or dynamically roll-tilted about the longitudinal axis. During monocular or binocular HOKS, when the rabbit was roll-tilted 30° onto the side of the eye stimulated in the posterior → anterior (P → A) direction, slow phase eye velocity (SPEV) increased by 3.5-5°/s. When the rabbit was roll-tilted 30° onto the side of the eye stimulated in the A → P direction, SPEV decreased to ~2.5°/s. We also tested the effect of roll-tilt after prolonged optokinetic stimulation had induced a negative optokinetic afternystagmus (OKAN II). In this condition, the SPEV occurred in the dark, "open loop." Modulation of SPEV of OKAN II depended on the direction of the nystagmus and was consistent with that observed during "closed loop" HOKS. Dynamic roll-tilt influenced SPEV evoked by HOKS in a similar way. The amplitude and the phase of SPEV depended on the frequency of vestibular oscillation and on HOKS velocity. We conclude that the change in the linear acceleration of the gravity vector with respect to the head during roll-tilt modulates the gain of SPEV depending on its direction. This modulation improves gaze stability at different image retinal slip velocities caused by head roll-tilt during centric or eccentric head movement.

The small molecule inhibitor QLT0267 Radiosensitizes squamous cell carcinoma cells of the head and neck.

Directory of Open Access Journals (Sweden)

Iris Eke

Full Text Available BACKGROUND: The constant increase of cancer cell resistance to radio- and chemotherapy hampers improvement of patient survival and requires novel targeting approaches. Integrin-Linked Kinase (ILK has been postulated as potent druggable cancer target. On the basis of our previous findings clearly showing that ILK transduces antisurvival signals in cells exposed to ionizing radiation, this study evaluated the impact of the small molecule inhibitor QLT0267, reported as putative ILK inhibitor, on the cellular radiation survival response of human head and neck squamous cell carcinoma cells (hHNSCC. METHODOLOGY/PRINCIPAL FINDINGS: Parental FaDu cells and FaDu cells stably transfected with a constitutively active ILK mutant (FaDu-IH or empty vectors, UTSCC45 cells, ILK(floxed/floxed(fl/fl and ILK(-/- mouse fibroblasts were used. Cells grew either two-dimensionally (2D on or three-dimensionally (3D in laminin-rich extracellular matrix. Cells were treated with QLT0267 alone or in combination with irradiation (X-rays, 0-6 Gy single dose. ILK knockdown was achieved by small interfering RNA transfection. ILK kinase activity, clonogenic survival, number of residual DNA double strand breaks (rDSB; gammaH2AX/53BP1 foci assay, cell cycle distribution, protein expression and phosphorylation (e.g. Akt, p44/42 mitogen-activated protein kinase (MAPK were measured. Data on ILK kinase activity and phosphorylation of Akt and p44/42 MAPK revealed a broad inhibitory spectrum of QLT0267 without specificity for ILK. QLT0267 significantly reduced basal cell survival and enhanced the radiosensitivity of FaDu and UTSCC45 cells in a time- and concentration-dependent manner. QLT0267 exerted differential, cell culture model-dependent effects with regard to radiogenic rDSB and accumulation of cells in the G2 cell cycle phase. Relative to corresponding controls, FaDu-IH and ILK(fl/fl fibroblasts showed enhanced radiosensitivity, which failed to be antagonized by QLT0267. A

Increased Dickkopf-1 expression accelerates bone cell apoptosis in femoral head osteonecrosis.

Science.gov (United States)

Ko, Jih-Yang; Wang, Feng-Sheng; Wang, Ching-Jen; Wong, To; Chou, Wen-Yi; Tseng, Shin-Ling

2010-03-01

Intensive bone cell apoptosis contributes to osteonecrosis of femoral head (ONFH). Dickkopf-1 (DKK1) reportedly mediates various types of skeletal disorders. This study investigated whether DKK1 was linked to the occurrence of ONFH. Thirty-nine patients with various stages of ONFH were recruited. Bone specimens were harvested from 34 ONFH patients underwent hip arthroplasty, and from 10 femoral neck fracture patients. Bad, Bcl2 TNFalpha, DKK1, Wnt3a, LRP5, and Axin1 expressions were analyzed by quantitative RT-PCR and ELISA. Apoptotic cells were assayed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labelling (TUNEL). Primary bone-marrow mesenchymal cells were treated with DKK1 RNA interference and recombinant DKK1 protein. ONFH patients with the histories of being administrated corticosteroids and excessive alcohol consumption had significantly higher Bad and DKK1 mRNA expressions in bone tissue and DKK1 abundances in serum than femoral neck fracture patients. Bone cells adjacent to osteonecrotic bone displayed strong DKK1 immunoreactivity and TUNEL staining. Increased DKK1 expression in bone tissue and serum correlated with Bad expression and TUNEL staining. Serum DKK1 abundance correlated with the severity of ONFH. The DKK1 RNA interference and recombinant DKK1 protein regulated Bad expression and apoptosis of primary bone-marrow mesenchymal cells. Knock down of DKK1 reduced dexamethasone-induced apoptosis of mesenchymal cells. Taken together, promoted DKK1 expression was associated with bone cell apoptosis in the occurrence of ONFH patients with the histories of corticosteroid and alcohol intake and progression of ONFH. DKK1 expression in injured tissue provides new insight into ONFH pathogenesis.

Sensing of substratum rigidity and directional migration by fast-crawling cells

Science.gov (United States)

Okimura, Chika; Sakumura, Yuichi; Shimabukuro, Katsuya; Iwadate, Yoshiaki

2018-05-01

Living cells sense the mechanical properties of their surrounding environment and respond accordingly. Crawling cells detect the rigidity of their substratum and migrate in certain directions. They can be classified into two categories: slow-moving and fast-moving cell types. Slow-moving cell types, such as fibroblasts, smooth muscle cells, mesenchymal stem cells, etc., move toward rigid areas on the substratum in response to a rigidity gradient. However, there is not much information on rigidity sensing in fast-moving cell types whose size is ˜10 μ m and migration velocity is ˜10 μ m /min . In this study, we used both isotropic substrata with different rigidities and an anisotropic substratum that is rigid on the x axis but soft on the y axis to demonstrate rigidity sensing by fast-moving Dictyostelium cells and neutrophil-like differentiated HL-60 cells. Dictyostelium cells exerted larger traction forces on a more rigid isotropic substratum. Dictyostelium cells and HL-60 cells migrated in the "soft" direction on the anisotropic substratum, although myosin II-null Dictyostelium cells migrated in random directions, indicating that rigidity sensing of fast-moving cell types differs from that of slow types and is induced by a myosin II-related process.

Infectious rotavirus enters cells by direct cell membrane penetration, not by endocytosis

International Nuclear Information System (INIS)

Kaljot, K.T.; Shaw, R.D.; Greenberg, H.B.; Rubin, D.H.

1988-01-01

Rotaviruses are icosahedral viruses with a segmented, double-stranded RNA genome. They are the major cause of severe infantile infectious diarrhea. Rotavirus growth in tissue culture is markedly enhanced by pretreatment of virus with trypsin. Trypsin activation is associated with cleavage of the viral hemagglutinin (viral protein 3 [VP3]; 88 kilodaltons) into two fragments (60 and 28 kilodaltons). The mechanism by which proteolytic cleavage leads to enhanced growth is unknown. To determine whether trypsin treatment affected rotavirus internalization, the authors studied the kinetics of entry of infectious rhesus rotavirus (RRV) into MA104 cells. Trypsin-activated RRV was internalized with a half-time of 3 to 5 min, while nonactivated virus disappeared from the cell surface with a half-time of 30 to 50 min. In contrast to trypsin-activated RRV, loss of nonactivated RRV from the cell surface did not result in the appearance of infection, as measured by plaque formation. Purified trypsin-activated RRV added to cell monolayers at pH 7.4 mediated 51 Cr, [ 14 C]choline, and [ 3 H]inositol released from prelabeled MA104 cells. This release could be specifically blocked by neutralizing antibodies to VP3. These results suggest that MA104 cell infection follows the rapid entry of trypsin-activated RRV by direct cell membrane penetration. Cell membrane penetration of infectious RRV is initiated by trypsin cleavage of VP3. Neutralizing antibodies can inhibit this direct membrane penetration

Infectious rotavirus enters cells by direct cell membrane penetration, not by endocytosis

Energy Technology Data Exchange (ETDEWEB)

Kaljot, K.T.; Shaw, R.D.; Greenberg, H.B. (Stanford Univ. School of Medicine, CA (USA) Palo Alto Veterans Administration Medical Center, CA (USA)); Rubin, D.H. (Univ. of Pennsylvania, Philadelphia (USA))

1988-04-01

Rotaviruses are icosahedral viruses with a segmented, double-stranded RNA genome. They are the major cause of severe infantile infectious diarrhea. Rotavirus growth in tissue culture is markedly enhanced by pretreatment of virus with trypsin. Trypsin activation is associated with cleavage of the viral hemagglutinin (viral protein 3 (VP3); 88 kilodaltons) into two fragments (60 and 28 kilodaltons). The mechanism by which proteolytic cleavage leads to enhanced growth is unknown. To determine whether trypsin treatment affected rotavirus internalization, the authors studied the kinetics of entry of infectious rhesus rotavirus (RRV) into MA104 cells. Trypsin-activated RRV was internalized with a half-time of 3 to 5 min, while nonactivated virus disappeared from the cell surface with a half-time of 30 to 50 min. In contrast to trypsin-activated RRV, loss of nonactivated RRV from the cell surface did not result in the appearance of infection, as measured by plaque formation. Purified trypsin-activated RRV added to cell monolayers at pH 7.4 mediated {sup 51}Cr, ({sup 14}C)choline, and ({sup 3}H)inositol released from prelabeled MA104 cells. This release could be specifically blocked by neutralizing antibodies to VP3. These results suggest that MA104 cell infection follows the rapid entry of trypsin-activated RRV by direct cell membrane penetration. Cell membrane penetration of infectious RRV is initiated by trypsin cleavage of VP3. Neutralizing antibodies can inhibit this direct membrane penetration.

Direct FuelCell/Turbine Power Plant

Energy Technology Data Exchange (ETDEWEB)

Hossein Ghezel-Ayagh

2008-09-30

This report summarizes the progress made in development of Direct FuelCell/Turbine (DFC/T{reg_sign}) power plants for generation of clean power at very high efficiencies. The DFC/T system employs an indirectly heated Turbine Generator to supplement fuel cell generated power. The concept extends the high efficiency of the fuel cell by utilizing the fuel cell's byproduct heat in a Brayton cycle. Features of the DFC/T system include: electrical efficiencies of up to 75% on natural gas, minimal emissions, reduced carbon dioxide release to the environment, simplicity in design, direct reforming internal to the fuel cell, and potential cost competitiveness with existing combined cycle power plants. Proof-of-concept tests using a sub-MW-class DFC/T power plant at FuelCell Energy's (FCE) Danbury facility were conducted to validate the feasibility of the concept and to measure its potential for electric power production. A 400 kW-class power plant test facility was designed and retrofitted to conduct the tests. The initial series of tests involved integration of a full-size (250 kW) Direct FuelCell stack with a 30 kW Capstone microturbine. The operational aspects of the hybrid system in relation to the integration of the microturbine with the fuel cell, process flow and thermal balances, and control strategies for power cycling of the system, were investigated. A subsequent series of tests included operation of the sub-MW Direct FuelCell/Turbine power plant with a Capstone C60 microturbine. The C60 microturbine extended the range of operation of the hybrid power plant to higher current densities (higher power) than achieved in initial tests using the 30kW microturbine. The proof-of-concept test results confirmed the stability and controllability of operating a fullsize (250 kW) fuel cell stack in combination with a microturbine. Thermal management of the system was confirmed and power plant operation, using the microturbine as the only source of fresh air supply

Effect of the Premalignant and Tumor Microenvironment on Immune Cell Cytokine Production in Head and Neck Cancer

Energy Technology Data Exchange (ETDEWEB)

Johnson, Sara D. [Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425 (United States); De Costa, Anna-Maria A. [Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, Charleston, SC 29425 (United States); Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425 (United States); Young, M. Rita I., E-mail: rita.young@va.gov [Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, Charleston, SC 29425 (United States); Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425 (United States); Medical Research Service (151), Ralph H. Johnson Veterans Affairs Medical Center, 109 Bee Street, Charleston, SC 29401 (United States)

2014-04-02

Head and neck squamous cell carcinoma (HNSCC) is marked by immunosuppression, a state in which the established tumor escapes immune attack. However, the impact of the premalignant and tumor microenvironments on immune reactivity has yet to be elucidated. The purpose of this study was to determine how soluble mediators from cells established from carcinogen-induced oral premalignant lesions and HNSCC modulate immune cell cytokine production. It was found that premalignant cells secrete significantly increased levels of G-CSF, RANTES, MCP-1, and PGE{sub 2} compared to HNSCC cells. Splenocytes incubated with premalignant supernatant secreted significantly increased levels of Th1-, Th2-, and Th17-associated cytokines compared to splenocytes incubated with HNSCC supernatant. These studies demonstrate that whereas the premalignant microenvironment elicits proinflammatory cytokine production, the tumor microenvironment is significantly less immune stimulatory and may contribute to immunosuppression in established HNSCC.

Manipulating directional cell motility using intracellular superparamagnetic nanoparticles

Science.gov (United States)

Bradshaw, Michael; Clemons, Tristan D.; Ho, Diwei; Gutiérrez, Lucía; Lázaro, Francisco J.; House, Michael J.; St. Pierre, Timothy G.; Fear, Mark W.; Wood, Fiona M.; Iyer, K. Swaminathan

2015-03-01

This study investigated the ability for magnetic nanoparticles to influence cellular migration in the presence of an external magnetic field. We found that the direction of migrating keratinocytes can be controlled and the migration speed of fibroblasts can be increased with the internalisation of these nanoparticles in the presence of a magnetic field. The possibility of shepherding cells towards a region of interest through the use of internalized nanoparticles is an attractive prospect for cell tracking, cell therapies, and tissue engineering applications.This study investigated the ability for magnetic nanoparticles to influence cellular migration in the presence of an external magnetic field. We found that the direction of migrating keratinocytes can be controlled and the migration speed of fibroblasts can be increased with the internalisation of these nanoparticles in the presence of a magnetic field. The possibility of shepherding cells towards a region of interest through the use of internalized nanoparticles is an attractive prospect for cell tracking, cell therapies, and tissue engineering applications. Electronic supplementary information (ESI) available: Nanoparticle characterisation, supporting experimental data, video time course study of cellular uptake of the nanoparticles and complete experimental details are all provided in the ESI. See DOI: 10.1039/c4nr06594h

Inhibition of Glutathione and Thioredoxin Metabolism Enhances Sensitivity to Perifosine in Head and Neck Cancer Cells

Directory of Open Access Journals (Sweden)

Andrean L. Simons

2009-01-01

Full Text Available The hypothesis that the Akt inhibitor, perifosine (PER, combined with inhibitors of glutathione (GSH and thioredoxin (Trx metabolism will induce cytotoxicity via metabolic oxidative stress in human head and neck cancer (HNSCC cells was tested. PER induced increases in glutathione disulfide (%GSSG in FaDu, Cal-27, and SCC-25 HNSCCs as well as causing significant clonogenic cell killing in FaDu and Cal-27, which was suppressed by simultaneous treatment with N-acetylcysteine (NAC. An inhibitor of GSH synthesis, buthionine sulfoximine (BSO, sensitized Cal-27 and SCC-25 cells to PER-induced clonogenic killing as well as decreased total GSH and increased %GSSG. Additionally, inhibition of thioredoxin reductase activity (TrxRed with auranofin (AUR was able to induce PER sensitization in SCC-25 cells that were initially refractory to PER. These results support the conclusion that PER induces oxidative stress and clonogenic killing in HNSCC cells that is enhanced with inhibitors of GSH and Trx metabolism.

Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review.

Science.gov (United States)

Hernandes, Camila; Pereira, Ana Maria Soares; Severino, Patricia

2017-02-01

Squamous cell carcinoma of the head and neck is one of the most common cancer types worldwide. It initiates on the epithelial lining of the upper aerodigestive tract, at most instances as a consequence of tobacco and alcohol consumption. Treatment options based on conventional therapies or targeted therapies under development have limited efficacy due to multiple genetic alterations typically found in this cancer type. Natural products derived from plants often possess biological activities that may be valuable in the development of new therapeutic agents for cancer treatment. Several genera from the family Celastraceae have been studied in this context. This review reports studies on chemical constituents isolated from species from the Celastraceae family targeting cancer mechanisms studied to date. These results are then correlated with molecular characteristics of head and neck squamous cell carcinoma in an attempt to identify constituents with potential application in the treatment of this complex disease at the molecular level.

Automatic cell identification and visualization using digital holographic microscopy with head mounted augmented reality devices.

Science.gov (United States)

O'Connor, Timothy; Rawat, Siddharth; Markman, Adam; Javidi, Bahram

2018-03-01

We propose a compact imaging system that integrates an augmented reality head mounted device with digital holographic microscopy for automated cell identification and visualization. A shearing interferometer is used to produce holograms of biological cells, which are recorded using customized smart glasses containing an external camera. After image acquisition, segmentation is performed to isolate regions of interest containing biological cells in the field-of-view, followed by digital reconstruction of the cells, which is used to generate a three-dimensional (3D) pseudocolor optical path length profile. Morphological features are extracted from the cell's optical path length map, including mean optical path length, coefficient of variation, optical volume, projected area, projected area to optical volume ratio, cell skewness, and cell kurtosis. Classification is performed using the random forest classifier, support vector machines, and K-nearest neighbor, and the results are compared. Finally, the augmented reality device displays the cell's pseudocolor 3D rendering of its optical path length profile, extracted features, and the identified cell's type or class. The proposed system could allow a healthcare worker to quickly visualize cells using augmented reality smart glasses and extract the relevant information for rapid diagnosis. To the best of our knowledge, this is the first report on the integration of digital holographic microscopy with augmented reality devices for automated cell identification and visualization.

A PET/CT-based strategy is a stronger predictor of survival than a standard imaging strategy in patients with head and neck squamous cell carcinoma

DEFF Research Database (Denmark)

Rohde, Max; Nielsen, Anne L; Pareek, Manan

2018-01-01

Purpose: To examine whether tumor staging by upfront (18)F-fluoro-deoxy-glucose-positron emission tomography/computed tomography (PET/CT) leads to improved discrimination of survival, when compared with traditionally used imaging strategies based on chest X-ray + head and neck magnetic resonance...... imaging (CXR/MRI) or chest computed tomography + head and neck MRI (CCT/MRI) in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Blinded prospective cohort study based on paired data. Consecutive patients with histologically verified primary HNSCC were recruited at Odense University...

Value of PET/CT 3D visualization of head and neck squamous cell carcinoma extended to mandible.

Science.gov (United States)

Lopez, R; Gantet, P; Julian, A; Hitzel, A; Herbault-Barres, B; Alshehri, S; Payoux, P

2018-05-01

To study an original 3D visualization of head and neck squamous cell carcinoma extending to the mandible by using [18F]-NaF PET/CT and [18F]-FDG PET/CT imaging along with a new innovative FDG and NaF image analysis using dedicated software. The main interest of the 3D evaluation is to have a better visualization of bone extension in such cancers and that could also avoid unsatisfying surgical treatment later on. A prospective study was carried out from November 2016 to September 2017. Twenty patients with head and neck squamous cell carcinoma extending to the mandible (stage 4 in the UICC classification) underwent [18F]-NaF and [18F]-FDG PET/CT. We compared the delineation of 3D quantification obtained with [18F]-NaF and [18F]-FDG PET/CT. In order to carry out this comparison, a method of visualisation and quantification of PET images was developed. This new approach was based on a process of quantification of radioactive activity within the mandibular bone that objectively defined the significant limits of this activity on PET images and on a 3D visualization. Furthermore, the spatial limits obtained by analysis of the PET/CT 3D images were compared to those obtained by histopathological examination of mandibular resection which confirmed intraosseous extension to the mandible. The [18F]-NaF PET/CT imaging confirmed the mandibular extension in 85% of cases and was not shown in [18F]-FDG PET/CT imaging. The [18F]-NaF PET/CT was significantly more accurate than [18F]-FDG PET/CT in 3D assessment of intraosseous extension of head and neck squamous cell carcinoma. This new 3D information shows the importance in the imaging approach of cancers. All cases of mandibular extension suspected on [18F]-NaF PET/CT imaging were confirmed based on histopathological results as a reference. The [18F]-NaF PET/CT 3D visualization should be included in the pre-treatment workups of head and neck cancers. With the use of a dedicated software which enables objective delineation of

Salinomycin induces cell death and differentiation in head and neck squamous cell carcinoma stem cells despite activation of epithelial-mesenchymal transition and Akt

International Nuclear Information System (INIS)

Kuo, Selena Z; Blair, Katherine J; Rahimy, Elham; Kiang, Alan; Abhold, Eric; Fan, Jian-Bing; Wang-Rodriguez, Jessica; Altuna, Xabier; Ongkeko, Weg M

2012-01-01

Cancer stem cells (CSC) are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells. MTS and TUNEL assays were used to study cell proliferation and apoptosis as a function of salinomycin exposure in JLO-1, a putative HNSCC stem cell culture. MTS and trypan blue dye exclusion assays were performed to investigate potential drug interactions between salinomycin and cisplatin or paclitaxel. Stem cell-like phenotype was measured by mRNA expression of stem cell markers, sphere-forming capacity, and matrigel invasion assays. Immunoblotting was also used to determine expression of epithelial-mesenchymal transition (EMT) markers and Akt phosphorylation. Arrays by Illumina, Inc. were used to profile microRNA expression as a function of salinomycin dose. In putative HNSCC stem cells, salinomycin was found to significantly inhibit cell viability, induce a 71.5% increase in levels of apoptosis, elevate the Bax/Bcl-2 ratio, and work synergistically with cisplatin and paclitaxel in inducing cell death. It was observed that salinomycin significantly inhibited sphere forming-capability and repressed the expression of CD44 and BMI-1 by 3.2-fold and 6.2-fold, respectively. Furthermore, salinomycin reduced invasion of HNSCC stem cells by 2.1 fold. Contrary to expectations, salinomycin induced the expression of EMT markers Snail, vimentin, and Zeb-1, decreased expression of E-cadherin, and also induced phosphorylation of Akt and its downstream targets GSK3-β and mTOR. These results demonstrate that in HNSCC cancer stem cells, salinomycin can cause cell death and decrease stem cell properties despite activation of both EMT and

Antitumor Activity of Rat Mesenchymal Stem Cells during Direct or Indirect Co-Culturing with C6 Glioma Cells.

Science.gov (United States)

Gabashvili, A N; Baklaushev, V P; Grinenko, N F; Mel'nikov, P A; Cherepanov, S A; Levinsky, A B; Chehonin, V P

2016-02-01

The tumor-suppressive effect of rat mesenchymal stem cells against low-differentiated rat C6 glioma cells during their direct and indirect co-culturing and during culturing of C6 glioma cells in the medium conditioned by mesenchymal stem cells was studied in an in vitro experiment. The most pronounced antitumor activity of mesenchymal stem cells was observed during direct co-culturing with C6 glioma cells. The number of live C6 glioma cells during indirect co-culturing and during culturing in conditioned medium was slightly higher than during direct co-culturing, but significantly differed from the control (C6 glioma cells cultured in medium conditioned by C6 glioma cells). The cytotoxic effect of medium conditioned by mesenchymal stem cells was not related to medium depletion by glioma cells during their growth. The medium conditioned by other "non-stem" cells (rat astrocytes and fibroblasts) produced no tumor-suppressive effect. Rat mesenchymal stem cells, similar to rat C6 glioma cells express connexin 43, the main astroglial gap junction protein. During co-culturing, mesenchymal stem cells and glioma C6 cells formed functionally active gap junctions. Gap junction blockade with connexon inhibitor carbenoxolone attenuated the antitumor effect observed during direct co-culturing of C6 glioma cells and mesenchymal stem cells to the level produced by conditioned medium. Cell-cell signaling mediated by gap junctions can be a mechanism of the tumor-suppressive effect of mesenchymal stem cells against C6 glioma cells. This phenomenon can be used for the development of new methods of cell therapy for high-grade malignant gliomas.

Tumor microenvironment in head and neck squamous cell carcinomas: predictive value and clinical relevance of hypoxic markers. A review.

Science.gov (United States)

Hoogsteen, Ilse J; Marres, Henri A M; Bussink, Johan; van der Kogel, Albert J; Kaanders, Johannes H A M

2007-06-01

Hypoxia and tumor cell proliferation are important factors determining the treatment response of squamous cell carcinomas of the head and neck. Successful approaches have been developed to counteract these resistance mechanisms although usually at the cost of increased short- and long-term side effects. To provide the best attainable quality of life for individual patients and the head and neck cancer patient population as a whole, it is of increasing importance that tools be developed that allow a better selection of patients for these intensified treatments. A literature review was performed with special focus on the predictive value and clinical relevance of endogenous hypoxia-related markers. New methods for qualitative and quantitative assessment of functional microenvironmental parameters such as hypoxia, proliferation, and vasculature have identified several candidate markers for future use in predictive assays. Hypoxia-related markers include hypoxia inducible factor (HIF)-1alpha, carbonic anhydrase IX, glucose transporters, erythropoietin receptor, osteopontin, and others. Although several of these markers and combinations of markers are associated with treatment outcome, their clinical value as predictive factors remains to be established. A number of markers and marker profiles have emerged that may have potential as a predictive assay. Validation of these candidate assays requires testing in prospective trials comparing standard treatment against experimental treatments targeting the related microregional constituent. (c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.

Direction, site and the muzzle target distance of bullet in the head and neck at close range as an indication of suicide or homicide.

Science.gov (United States)

Suwanjutha, T

1988-05-01

Direction, site and muzzle target distance can indicate suicide or homicide. This conclusion can be drawn from autopsies of 57 cases of suicide and 68 cases of homicide by handgun fired at close range to the head and neck together with going to the crimescene in some cases. This study was carried out in Bangkok during the period from January 1983 to January 1986. In order to determine whether it was suicide or homicide, the path of the bullet, the site, the muzzle target distance must be considered. The angle of the bullet would be either elevated (from below upward), horizontal or an angle of depression (from above downward). For suicide, the direction of the bullet should be at an angle of elevation in the majority of cases. The position of the handgun in relation to the head in suicide was most often in tight contact and near contact. For homicide, the direction of the bullet should be horizontal in most cases. The bullet was at close range in the majority of the cases. There are 8 common sites for suicide and homicide and 10 different sites in the case of homicide which are at neck, left cheek, left aural region, lip, left occipital area orbit, chin, left eyebrow, submental and nose.

Is Dosage Important? Examining Head Start Preschoolers' Language and Literacy Learning after One versus Two Years of "ExCELL"

Science.gov (United States)

Hindman, Annemarie H.; Wasik, Barbara A.

2017-01-01

The current study examined whether Head Start children who experienced a high-quality preschool intervention, "Exceptional Coaching for Early Language and Literacy" ("ExCELL"), as three-year-olds began the subsequent pre-kindergarten (or four-year-old) year with stronger language and literacy skills than same-age peers who…

Pravastatin Protects Against Avascular Necrosis of Femoral Head via Autophagy.

Science.gov (United States)

Liao, Yun; Zhang, Ping; Yuan, Bo; Li, Ling; Bao, Shisan

2018-01-01

Autophagy serves as a stress response and may contribute to the pathogenesis of avascular necrosis of the femoral head induced by steroids. Statins promote angiogenesis and ameliorate endothelial functions through apoptosis inhibition and necrosis of endothelial progenitor cells, however the process used by statins to modulate autophagy in avascular necrosis of the femoral head remains unclear. This manuscript determines whether pravastatin protects against dexamethasone-induced avascular necrosis of the femoral head by activating endothelial progenitor cell autophagy. Pravastatin was observed to enhance the autophagy activity in endothelial progenitor cells, specifically by upregulating LC3-II/Beclin-1 (autophagy related proteins), and autophagosome formation in vivo and in vitro . An autophagy inhibitor, 3-MA, reduced pravastatin protection in endothelial progenitor cells exposed to dexamethasone by attenuating pravastatin-induced autophagy. Adenosine monophosphate-activated protein kinase (AMPK) is a key autophagy regulator by sensing cellular energy changes, and indirectly suppressing activation of the mammalian target of rapamycin (mTOR). We found that phosphorylation of AMPK was upregulated however phosphorylation of mTOR was downregulated in pravastatin-treated endothelial progenitor cells, which was attenuated by AMPK inhibitor compound C. Furthermore, liver kinase B1 (a phosphorylase of AMPK) knockdown eliminated pravastatin regulated autophagy protein LC3-II in endothelial progenitor cells in vitro . We therefore demonstrated pravastatin rescued endothelial progenitor cells from dexamethasone-induced autophagy dysfunction through the AMPK-mTOR signaling pathway in a liver kinase B1-dependent manner. Our results provide useful information for the development of novel therapeutics for management of glucocorticoids-induced avascular necrosis of the femoral head.

Long head of the biceps brachii tendon: unenhanced MRI versus direct MR arthrography

Energy Technology Data Exchange (ETDEWEB)

Tadros, Anthony S.; Huang, Brady K. [University of California, Department of Radiology, San Diego, CA (United States); Wymore, Lucas; Hoenecke, Heinz; Fronek, Jan [Scripps Clinic, Department of Orthopedic Surgery, La Jolla, CA (United States); Chang, Eric Y. [VA San Diego Healthcare System, Radiology Service, San Diego, CA (United States); University of California, Department of Radiology, San Diego, CA (United States)

2015-09-15

We sought to determine the diagnostic accuracy of unenhanced MRI and direct MR arthrography (MRA) for evaluation of the intra-articular long head of the biceps brachii tendon (LHBT) using arthroscopy as the gold standard. A retrospective review of patients who underwent shoulder MRI (n = 132) and MRA (n = 67) within 12 months prior to arthroscopy was performed. MR images were independently reviewed by two blinded musculoskeletal radiologists. Routinely recorded arthroscopic photos/videos were reviewed by an orthopedic surgeon. The LHBT was graded as normal, tendinosis, partial thickness tear less or greater than 50 %, and complete tear. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for tendinosis and tear detection were calculated. MRI correctly diagnosed fewer normal LHBTs compared to MRA (39-54 % versus 74-84 %, respectively; p < 0.005). MRI and MRA did not differ significantly in the diagnosis of tendinosis (18-36 % and 15-38 %, respectively; p > 0.05) and tears (75-83 % and 64-73 %, respectively; p > 0.05). For tendinosis, MRI versus MRA showed 18-36 % and 15-38 % sensitivity, 69-79 % and 83-91 % specificity, 22-28 % and 18-50 % PPV, 74-76 % and 80-86 % NPV, and 61-64 % and 70-81 % accuracy; respectively. For tears, MRI versus MRA showed 75-83 % and 64-73 % sensitivity, 73-75 % and 82-91 % specificity, 66-69 % and 41-62 % PPV, 82-87 % and 92-94 % NPV, and 74-78 % and 79-88 % accuracy; respectively. No significant difference was found between unenhanced MRI and direct MRA for the detection of tendinosis and tears of LHBTs. (orig.)

Long head of the biceps brachii tendon: unenhanced MRI versus direct MR arthrography

International Nuclear Information System (INIS)

Tadros, Anthony S.; Huang, Brady K.; Wymore, Lucas; Hoenecke, Heinz; Fronek, Jan; Chang, Eric Y.

2015-01-01

We sought to determine the diagnostic accuracy of unenhanced MRI and direct MR arthrography (MRA) for evaluation of the intra-articular long head of the biceps brachii tendon (LHBT) using arthroscopy as the gold standard. A retrospective review of patients who underwent shoulder MRI (n = 132) and MRA (n = 67) within 12 months prior to arthroscopy was performed. MR images were independently reviewed by two blinded musculoskeletal radiologists. Routinely recorded arthroscopic photos/videos were reviewed by an orthopedic surgeon. The LHBT was graded as normal, tendinosis, partial thickness tear less or greater than 50 %, and complete tear. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for tendinosis and tear detection were calculated. MRI correctly diagnosed fewer normal LHBTs compared to MRA (39-54 % versus 74-84 %, respectively; p < 0.005). MRI and MRA did not differ significantly in the diagnosis of tendinosis (18-36 % and 15-38 %, respectively; p > 0.05) and tears (75-83 % and 64-73 %, respectively; p > 0.05). For tendinosis, MRI versus MRA showed 18-36 % and 15-38 % sensitivity, 69-79 % and 83-91 % specificity, 22-28 % and 18-50 % PPV, 74-76 % and 80-86 % NPV, and 61-64 % and 70-81 % accuracy; respectively. For tears, MRI versus MRA showed 75-83 % and 64-73 % sensitivity, 73-75 % and 82-91 % specificity, 66-69 % and 41-62 % PPV, 82-87 % and 92-94 % NPV, and 74-78 % and 79-88 % accuracy; respectively. No significant difference was found between unenhanced MRI and direct MRA for the detection of tendinosis and tears of LHBTs. (orig.)

Application of directional solidification ingot (LSD) in forging of PWR reactor vessel heads

International Nuclear Information System (INIS)

Benhamou, C.; Poitrault, I.

1985-09-01

Creusot-Loire Industrie uses this type of ingot for manufacture of Framatome 1300 and 1450 MW 4-loop PWR reactor vessel heads. This type of ingot offers a number advantages: improved internal soundness; greater chemical, structural and mechanical homogeneity of the finished part; simplified forging process. After a brief description of the pouring and solidification processes, this paper presents an analysis of the results of examinations performed on the prototype forging, as well as review of results obtained during industrial fabrication of dished heads from LSD ingots. The advantages of the LSD ingot over conventional ingots are discussed in conclusion

Down-regulation of survivin by oxaliplatin diminishes radioresistance of head and neck squamous carcinoma cells

International Nuclear Information System (INIS)

Khan, Zakir; Khan, Noor; Tiwari, Ram P.; Patro, Ishan K.; Prasad, G.B.K.S.; Bisen, Prakash S.

2010-01-01

Background: Oxaliplatin is integrated in treatment strategies against a variety of cancers including radiation protocols. Herein, as a new strategy we tested feasibility and rationale of oxaliplatin in combination with radiation to control proliferation of head and neck squamous cell carcinoma (HNSCC) cells and discussed survivin-related signaling and apoptosis induction. Methods: Cytotoxicity and apoptosis induced by radiation and/or oxaliplatin were examined in relation to survivin status using two HNSCC cell lines viz., Cal27 and NT8e, and one normal 293-cell line. Survivin gene knockdown by siRNA was also tested in relevance to oxaliplatin-mediated radiosensitization effects. Results: Survivin plays a critical role in mediating radiation-resistance in part through suppression of apoptosis via a caspase-dependent mechanism. Oxaliplatin treatment significantly decreased expression of survivin in cancer cells within 24-72 h. Apoptotic cells and caspase-3 activity were increased parallely with decrease in cell viability, if irradiated during this sensitive period. The cytotoxicity of oxaliplatin and radiation combination was greater than additive. Survivin gene knockdown experiments have demonstrated the role of survivin in radiosensitization of cancer cells mediated by oxaliplatin. Conclusions: Higher expression of survivin is a critical factor for radioresistance in HNSCC cell lines. Pre-treatment of cancer cells with oxaliplatin significantly increased the radiosensitivity through induction of apoptosis by potently inhibiting survivin.

Head and neck squamous cell carcinoma and its correlation with human papillomavirus in people living with HIV: a systematic review.

Science.gov (United States)

Ceccarelli, Manuela; Rullo, Emmanuele Venanzi; Facciolà, Alessio; Madeddu, Giordano; Cacopardo, Bruno; Taibi, Rosaria; D'Aleo, Francesco; Pinzone, Marilia Rita; Picerno, Isa; di Rosa, Michele; Visalli, Giuseppa; Condorelli, Fabrizio; Nunnari, Giuseppe; Pellicanò, Giovanni Francesco

2018-03-30

Over the last 20 years we assisted to an increase in the mean age of People Living with HIV and their comorbidities. Especially, there was an increase in Human Papillomavirus-related head and neck squamous cell carcinomas. Despite their increasing incidence in HIV-positive people, mechanisms that lead to their development and progression are only partially understood. The aim of this review is to identify key data and factors about HPV-related head and neck squamous cell carcinoma in HIV-seropositive patients. Systematic search and review of the relevant literature-peer-reviewed and grey-was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. We included in our review only the 35 full-text articles we considered the most substantial. It is mandatory to improve our knowledge about the interactions existing between HPV and HIV, and about their actions on oral mucosa immune system.

Osteonecrosis of the femoral head in sickle cell disease: prevalence, comorbidities, and surgical outcomes in California

OpenAIRE

Adesina, Oyebimpe; Brunson, Ann; Keegan, Theresa H. M.; Wun, Ted

2017-01-01

Osteonecrosis of the femoral head (ONFH) is a prevalent complication of sickle cell disease (SCD) that has not been well described in population-based cohort studies. Using California's Office of Statewide Planning and Development discharge databases (1991-2013), we estimated the cumulative incidence of ONFH after accounting for the competing risk of death and used a multivariable Cox proportional hazards regression to identify factors associated with ONFH diagnosis. We also calculated rates ...

Compliance and toxicity of the hypoxic radiosensitizer nimorazole in the treatment of patients with head and neck squamous cell carcinoma (HNSCC)

DEFF Research Database (Denmark)

Metwally, Mohamed Ahmed Hassan; Frederiksen, Katrine Diemer; Overgaard, Jens

2014-01-01

Abstract Purpose. To evaluate the compliance and toxicity of the hypoxic radiosensitizer nimorazole in head and neck cancer patients. Methods. A retrospective study of patients with head and neck squamous cell carcinoma (HNSCC), treated in Denmark between 1990 and 2013. All patients treated...... with radical radiotherapy (± chemotherapy) [66-70 Gy; 33-35 fractions; 2 Gy/fraction; 5-6 fractions/week] concomitant with the hypoxic radiosensitizer nimorazole. Nimorazole was administered as oral tablets in doses of approximately 1.2 g/m(2) body surface area in connection with the first of each daily...

Detection of human papillomavirus (HPV) type 6, 16 and 18 in head and neck squamous cell carcinomas by in situ hybridization

International Nuclear Information System (INIS)

Cerovac, Z.; Sarcevic, B.; Kralj, Z.; Ban, J.

1996-01-01

Seventy seven squamous cell carcinomas (10 oral cavity, 15 tongue, 26 pharynx and larynx), with different grading were analyzed for the presence of HPV DNA by in situ hybridization. Positive signals were found on the nuclei of cancer cells in 25 (32.5%), in the epithelia adjacent to squamous cell carcinomas in 2 (8.7%), and in the resected margins in 1 (4.3%) case. HPV DNA positive signals were obtained in 42% of laryngeal, 34% of pharyngeal, in 20% of oral, and 20% of tongue carcinomas. Out of 25 HPV positive carcinomas a single HPV type was detected in at least 11 (44%), and double or multiple infection in 36% cases; altogether , HPV 6 DNA was determined in 15 (60%), and HPV 16 and/or 18 DNA in 17 (68%) head and neck tumors. The detection rate of HPV was lower than of HPV 16 and/or 18 for tumors in oral cavity, tongue and larynx. Out of 25 HPV DNA positive carcinomas 21% were graded as G1, 27% as G2, and and 44% were G3. The results indicate that HPV may be involved in the pathogenesis of head and neck squamous cell carcinomas. (author)

Oral sex and human papilloma virus-related head and neck squamous cell cancer: a review of the literature.

Science.gov (United States)

Shah, Ankit; Malik, Akshat; Garg, Apurva; Mair, Manish; Nair, Sudhir; Chaturvedi, Pankaj

2017-11-01

Head neck squamous cell carcinomas (HNSCCs) are a significant cause of morbidity and mortality all around the world. Just like tobacco and alcohol, Human papilloma virus (HPV) infection is now recognized to play a role in the pathogenesis of a subset of HNSCCs. Unprotected sexual behaviours with the HPV carrier plays an important role in transmission of this virus. The global incidence of head and neck cancers is declining, but the incidence of HPV related head and neck cancers is rapidly increasing over the last few decades. However, most institutions do not mandate documentation of sexual history or counselling of patients regarding sexual practices like they do for tobacco and alcohol addictions in HNSCC patients. The aim of this review of literature is to analyse if there is a strong evidence to correlate oral sex with HPV related HNSCC and counsel the patient's regarding sexual behaviours. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

PET of EGFR with (64) Cu-cetuximab-F(ab')2 in mice with head and neck squamous cell carcinoma xenografts

NARCIS (Netherlands)

Dijk, L.K. van; Yim, C.B.; Franssen, G.M.; Kaanders, J.H.; Rajander, J.; Solin, O.; Gronroos, T.J.; Boerman, O.C.; Bussink, J.

2016-01-01

Overexpression of the epidermal growth factor receptor (EGFR) is linked to an adverse outcome in various solid tumors. Cetuximab is an EGFR inhibitor, which in combination with radiotherapy improves locoregional control and survival in a subgroup of patients with head and neck squamous cell

Recent advances on Zeolite modification for direct alcohol fuel cells (DAFCs)

Science.gov (United States)

Makertihartha, I. G. B. N.; Zunita, M.; Rizki, Z.; Dharmawijaya, P. T.

2017-03-01

The increase of energy demand and global warming issues has driven studies of alternative energy sources. The polymer electrolyte membrane fuel cell (PEMFC) can be an alternative energy source by (partially) replacing the use of fossil fuel which is in line with the green technology concept. However, the usage of hydrogen as a fuel has several disadvantages mainly transportation and storage related to its safety aspects. Recently, alcohol has gained attention as an energy source for fuel cell application, namely direct alcohol fuel cell (DAFC). Among alcohols, high-mass energy density methanol and ethanol are widely used as direct methanol fuel cell (DMFC) and direct ethanol fuel cell (DEFC), respectively. Currently, the performance of DMFC is still rudimentary. Furthermore, the use of ethanol gives some additional privileges such as non-toxic property, renewable, ease of production in great quantity by the fermentation of sugar-containing raw materials. Direct alcohol fuel cell (DAFC) still has weakness in the low proton conductivity and high alcohol crossover. Therefore, to increase the performance of DAFC, modification using zeolite has been performed to improve proton conductivity and decrease alcohol crossover. Zeolite also has high thermal resistance properties, thereby increasing DAFC performance. This paper will discuss briefly about modification of catalyst and membrane for DAFC using zeolite. Zeolite modification effect on fuel cell performance especially proton conductivity and alcohol crossover will be presented in detail.

Audiovisual Head Orientation Estimation with Particle Filtering in Multisensor Scenarios

Directory of Open Access Journals (Sweden)

Javier Hernando

2007-07-01

Full Text Available This article presents a multimodal approach to head pose estimation of individuals in environments equipped with multiple cameras and microphones, such as SmartRooms or automatic video conferencing. Determining the individuals head orientation is the basis for many forms of more sophisticated interactions between humans and technical devices and can also be used for automatic sensor selection (camera, microphone in communications or video surveillance systems. The use of particle filters as a unified framework for the estimation of the head orientation for both monomodal and multimodal cases is proposed. In video, we estimate head orientation from color information by exploiting spatial redundancy among cameras. Audio information is processed to estimate the direction of the voice produced by a speaker making use of the directivity characteristics of the head radiation pattern. Furthermore, two different particle filter multimodal information fusion schemes for combining the audio and video streams are analyzed in terms of accuracy and robustness. In the first one, fusion is performed at a decision level by combining each monomodal head pose estimation, while the second one uses a joint estimation system combining information at data level. Experimental results conducted over the CLEAR 2006 evaluation database are reported and the comparison of the proposed multimodal head pose estimation algorithms with the reference monomodal approaches proves the effectiveness of the proposed approach.

Small cell carcinoma of the head and neck: A comparative study by primary site based on population data.

Science.gov (United States)

Kuan, Edward C; Alonso, Jose E; Tajudeen, Bobby A; Arshi, Armin; Mallen-St Clair, Jon; St John, Maie A

2017-08-01

Small cell carcinoma (SmCC) of the head and neck is an extremely rare neuroendocrine malignancy. In this study, we describe the incidence and determinants of survival of patients with SmCC of the head and neck between the years of 1973 and 2012 using the Surveillance, Epidemiology, and End Results database as differed by primary site. Retrospective, population-based cohort study. A total of 237 cases of SmCC of the head and neck were identified, which was divided into sinonasal primaries (n = 82) and all other head and neck primaries (n = 155). Clinicopathologic and epidemiologic variables were analyzed as predictors of overall survival (OS) and disease-specific survival (DSS) based on the Kaplan-Meier method. More than half of sinonasal primaries presented with Kadish stage C or D. On multivariate analysis, surgery was the only independent predictor of improved DSS (P = .008) for sinonasal primaries; in contrast, radiation therapy was a favorable prognosticator for OS (P = .007) and DSS (P = .043) in extrasinonasal sites. Comparison of survival between sinonasal primaries and all other sites demonstrated that sinonasal SmCC had uniformly better OS (P = .002) and DSS (P = .006). SmCC in the head and neck remains rare, and sinonasal primaries appear to have improved survival compared to other sites. Based on these results, optimal treatment for sinonasal SmCC appears to be surgical therapy, whereas radiation therapy is the preferred treatment for SmCC of other primary sites, particularly the larynx. 4. Laryngoscope, 127:1785-1790, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Immunohistochemical and molecular imaging biomarker signature for the prediction of failure site after chemoradiation for head and neck squamous cell carcinoma

DEFF Research Database (Denmark)

Rasmussen, Gregers Brünnich; Håkansson, Katrin E; Vogelius, Ivan R

2017-01-01

.23; p: .025), Bcl-2 (HR: 2.6; p: .08), SUVmax (HR: 3.5; p: .095) and GTV (HR: 1.7; p: .063). CONCLUSIONS: The models successfully distinguished between risk of locoregional failure and risk of distant metastasis, which is important information for clinical decision-making. High p53 expression has......OBJECTIVE: To identify a failure site-specific prognostic model by combining immunohistochemistry (IHC) and molecular imaging information to predict long-term failure type in squamous cell carcinoma of the head and neck. PATIENT AND METHODS: Tissue microarray blocks of 196 head and neck squamous...... cell carcinoma cases were stained for a panel of biomarkers using IHC. Gross tumor volume (GTV) from the PET/CT radiation treatment planning CT scan, maximal Standard Uptake Value (SUVmax) of fludeoxyglucose (FDG) and clinical information were included in the model building using Cox proportional...

Analytical modelling of soccer heading

Indian Academy of Sciences (India)

... game is that the players are permitted to use their head to direct the ball during ... method in assessing the cognitive functions that can be applied not only to ... It is attached to a spring (stiffness, k1) and a dashpot (damping coefficient, c1).

Risk factors for head injury events in professional rugby union: a video analysis of 464 head injury events to inform proposed injury prevention strategies.

Science.gov (United States)

Tucker, Ross; Raftery, Martin; Kemp, Simon; Brown, James; Fuller, Gordon; Hester, Ben; Cross, Matthew; Quarrie, Ken

2017-08-01

The tackle is responsible for the majority of head injuries during rugby union. In order to address head injury risk, risk factors during the tackle must first be identified. This study analysed tackle characteristics in the professional game in order to inform potential interventions. 464 tackles resulting in a head injury assessment (HIA) were analysed in detail, with tackle type, direction, speed, acceleration, nature of head contact and player body position the characteristics of interest. Propensity to cause an HIA was significantly greater for active shoulder tackles, front-on tackles, high speeder tackles and an accelerating tackler. Head contact between a tackler's head and ball carrier's head or shoulder was significantly more likely to cause an HIA than contact below the level of the shoulder (incident rate ratio (IRR) 4.25, 95%-CI 3.38 to 5.35). The tackler experiences the majority (78%) of HIAs when head-to-head contact occurs. An upright tackler was 1.5 times more likely to experience an HIA than a bent at the waist tackler (IRR 1.44, 95% CI 1.18 to 1.76). This study confirms that energy transfer in the tackle is a risk factor for head injury, since direction, type and speed all influence HIA propensity. The study provides evidence that body position and the height of tackles should be a focus for interventions, since lowering height and adopting a bent at the waist body position is associated with reduced risk for both tacklers and ball carriers. To this end, World Rugby has implemented law change based on the present data. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Improved head direction command classification using an optimised Bayesian neural network.

Science.gov (United States)

Nguyen, Son T; Nguyen, Hung T; Taylor, Philip B; Middleton, James

2006-01-01

Assistive technologies have recently emerged to improve the quality of life of severely disabled people by enhancing their independence in daily activities. Since many of those individuals have limited or non-existing control from the neck downward, alternative hands-free input modalities have become very important for these people to access assistive devices. In hands-free control, head movement has been proved to be a very effective user interface as it can provide a comfortable, reliable and natural way to access the device. Recently, neural networks have been shown to be useful not only for real-time pattern recognition but also for creating user-adaptive models. Since multi-layer perceptron neural networks trained using standard back-propagation may cause poor generalisation, the Bayesian technique has been proposed to improve the generalisation and robustness of these networks. This paper describes the use of Bayesian neural networks in developing a hands-free wheelchair control system. The experimental results show that with the optimised architecture, classification Bayesian neural networks can detect head commands of wheelchair users accurately irrespective to their levels of injuries.

Analysis of antigen-specific B-cell memory directly ex vivo.

Science.gov (United States)

McHeyzer-Williams, Louise J; McHeyzer-Williams, Michael G

2004-01-01

Helper T-cell-regulated B-cell memory develops in response to initial antigen priming as a cellular product of the germinal center (GC) reaction. On antigen recall, memory response precursors expand rapidly with exaggerated differentiation into plasma cells to produce the high-titer, high-affinity antibody(Ab) that typifies the memory B-cell response in vivo. We have devised a high-resolution flow cytometric strategy to quantify the emergence and maintenance of antigen-specific memory B cells directly ex vivo. Extended cell surface phenotype establishes a level of cellular diversity not previously appreciated for the memory B-cell compartment. Using an "exclusion transfer" strategy, we ascertain the capacity of two distinct memory B-cell populations to transfer antigen-specific memory into naive adoptive hosts. Finally, we sequence expressed messenger ribonucleic acid (mRNA) from single cells within the population to estimate the level of somatic hypermutation as the best molecular indicator of B-cell memory. In this chapter, we describe the methods used in each of these four sections that serve to provide high-resolution quantification of antigen-specific B-cell memory responses directly ex vivo.

Direct Coal Oxidation in Modified Solid Oxide Fuel Cells

DEFF Research Database (Denmark)

Deleebeeck, Lisa; Gil, Vanesa; Ippolito, Davide

2017-01-01

Hybrid direct carbon fuel cells employ a classical solid oxide fuel cell together with carbon dispersed in a carbonate melt on the anode side. In a European project, the utilization of various coals has been investigated with and without addition of an oxidation catalyst to the carbon-carbonate s......Hybrid direct carbon fuel cells employ a classical solid oxide fuel cell together with carbon dispersed in a carbonate melt on the anode side. In a European project, the utilization of various coals has been investigated with and without addition of an oxidation catalyst to the carbon......-carbonate slurry or anode layer. The nature of the coal affects both open circuit voltage and power output. Highest OCV and power densities were observed for bituminous coal and by adding manganese oxide or praseodymium-doped ceria to the carbon/carbonate mixture. Comparing the carbon black fueled performance...... bituminous coal (73 mW/cm2)....

Radiation-Induced Dedifferentiation of Head and Neck Cancer Cells Into Cancer Stem Cells Depends on Human Papillomavirus Status

International Nuclear Information System (INIS)

Vlashi, Erina; Chen, Allen M.; Boyrie, Sabrina; Yu, Garrett; Nguyen, Andrea; Brower, Philip A.; Hess, Clayton B.; Pajonk, Frank

2016-01-01

Purpose: To test the hypothesis that the radiation response of cancer stem cells (CSCs) in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) differs and is not reflected in the radiation response of the bulk tumor populations, that radiation therapy (RT) can dedifferentiate non-stem HNSCC cells into CSCs, and that radiation-induced dedifferentiation depends on the HPV status. Methods and Materials: Records of a cohort of 162 HNSCC patients were reviewed, and their outcomes were correlated with their HPV status. Using a panel of HPV-positive and HPV-negative HNSCC cell lines expressing a reporter for CSCs, we characterized HPV-positive and HPV-negative lines via flow cytometry, sphere-forming capacity assays in vitro, and limiting dilution assays in vivo. Non-CSCs were treated with different doses of radiation, and the dedifferentiation of non-CSCs into CSCs was investigated via flow cytometry and quantitative reverse transcription–polymerase chain reaction for re-expression of reprogramming factors. Results: Patients with HPV-positive tumors have superior overall survival and local–regional control. Human papillomavirus–positive HNSCC cell lines have lower numbers of CSCs, which inversely correlates with radiosensitivity. Human papillomavirus–negative HNSCC cell lines lack hierarchy owing to enhanced spontaneous dedifferentiation. Non-CSCs from HPV-negative lines show enhanced radiation-induced dedifferentiation compared with HPV-positive lines, and RT induced re-expression of Yamanaka reprogramming factors. Conclusions: Supporting the favorable prognosis of HPV-positive HNSCCs, we show that (1) HPV-positive HNSCCs have a lower frequency of CSCs; (2) RT can dedifferentiate HNSCC cells into CSCs; and (3) radiation-induced dedifferentiation depends on the HPV status of the tumor.

Radiation-Induced Dedifferentiation of Head and Neck Cancer Cells Into Cancer Stem Cells Depends on Human Papillomavirus Status

Energy Technology Data Exchange (ETDEWEB)

Vlashi, Erina, E-mail: evlashi@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California (United States); Chen, Allen M.; Boyrie, Sabrina; Yu, Garrett; Nguyen, Andrea; Brower, Philip A. [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); Hess, Clayton B. [Department of Radiation Oncology, University of California Davis, Sacramento, California (United States); Pajonk, Frank [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California (United States)

2016-04-01

Purpose: To test the hypothesis that the radiation response of cancer stem cells (CSCs) in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) differs and is not reflected in the radiation response of the bulk tumor populations, that radiation therapy (RT) can dedifferentiate non-stem HNSCC cells into CSCs, and that radiation-induced dedifferentiation depends on the HPV status. Methods and Materials: Records of a cohort of 162 HNSCC patients were reviewed, and their outcomes were correlated with their HPV status. Using a panel of HPV-positive and HPV-negative HNSCC cell lines expressing a reporter for CSCs, we characterized HPV-positive and HPV-negative lines via flow cytometry, sphere-forming capacity assays in vitro, and limiting dilution assays in vivo. Non-CSCs were treated with different doses of radiation, and the dedifferentiation of non-CSCs into CSCs was investigated via flow cytometry and quantitative reverse transcription–polymerase chain reaction for re-expression of reprogramming factors. Results: Patients with HPV-positive tumors have superior overall survival and local–regional control. Human papillomavirus–positive HNSCC cell lines have lower numbers of CSCs, which inversely correlates with radiosensitivity. Human papillomavirus–negative HNSCC cell lines lack hierarchy owing to enhanced spontaneous dedifferentiation. Non-CSCs from HPV-negative lines show enhanced radiation-induced dedifferentiation compared with HPV-positive lines, and RT induced re-expression of Yamanaka reprogramming factors. Conclusions: Supporting the favorable prognosis of HPV-positive HNSCCs, we show that (1) HPV-positive HNSCCs have a lower frequency of CSCs; (2) RT can dedifferentiate HNSCC cells into CSCs; and (3) radiation-induced dedifferentiation depends on the HPV status of the tumor.

Direct Cell-Cell Contact between Mesenchymal Stem Cells and Endothelial Progenitor Cells Induces a Pericyte-Like Phenotype In Vitro

Directory of Open Access Journals (Sweden)

Markus Loibl

2014-01-01

Full Text Available Tissue engineering techniques for the regeneration of large bone defects require sufficient vascularisation of the applied constructs to ensure a sufficient supply of oxygen and nutrients. In our previous work, prevascularised 3D scaffolds have been successfully established by coculture of bone marrow derived stem cells (MSCs and endothelial progenitor cells (EPCs. We identified stabilising pericytes (PCs as part of newly formed capillary-like structures. In the present study, we report preliminary data on the interactions between MSCs and EPCs, leading to the differentiation of pericyte-like cells. MSCs and EPCs were seeded in transwell cultures, direct cocultures, and single cultures. Cells were cultured for 10 days in IMDM 10% FCS or IMDM 5% FCS 5% platelet lysate medium. Gene expression of PC markers, CD146, NG2, αSMA, and PDGFR-β, was analysed using RT-PCR at days 0, 3, 7, and 10. The upregulation of CD146, NG2, and αSMA in MSCs in direct coculture with EPCs advocates the MSCs’ differentiation towards a pericyte-like phenotype in vitro. These results suggest that pericyte-like cells derive from MSCs and that cell-cell contact with EPCs is an important factor for this differentiation process. These findings emphasise the concept of coculture strategies to promote angiogenesis for cell-based tissue engineered bone grafts.

Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected].

NARCIS (Netherlands)

Stewart, J.S.; Cohen, E.E.; Licitra, L.; Herpen, C.M.L. van; Khorprasert, C.; Soulieres, D.; Vodvarka, P.; Rischin, D.; Garin, A.M.; Hirsch, F.R.; Varella-Garcia, M.; Ghiorghiu, S.; Hargreaves, L.; Armour, A.; Speake, G.; Swaisland, A.; Vokes, E.E.

2009-01-01

PURPOSE: To compare survival in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with gefitinib 250 or 500 mg/day or standard methotrexate. PATIENTS AND METHODS: Four hundred eighty-six patients with recurrent SCCHN were randomly assigned to oral

Inhibition of radiation induced migration of human head and neck squamous cell carcinoma cells by blocking of EGF receptor pathways

International Nuclear Information System (INIS)

Pickhard, Anja C; Schlegel, Jürgen; Arnold, Wolfgang; Reiter, Rudolf; Margraf, Johanna; Knopf, Andreas; Stark, Thomas; Piontek, Guido; Beck, Carolin; Boulesteix, Anne-Laure; Scherer, Elias Q; Pigorsch, Steffi

2011-01-01

Recently it has been shown that radiation induces migration of glioma cells and facilitates a further spread of tumor cells locally and systemically. The aim of this study was to evaluate whether radiotherapy induces migration in head and neck squamous cell carcinoma (HNSCC). A further aim was to investigate the effects of blocking the epidermal growth factor receptor (EGFR) and its downstream pathways (Raf/MEK/ERK, PI3K/Akt) on tumor cell migration in vitro. Migration of tumor cells was assessed via a wound healing assay and proliferation by a MTT colorimeritric assay using 3 HNSCC cell lines (BHY, CAL-27, HN). The cells were treated with increasing doses of irradiation (2 Gy, 5 Gy, 8 Gy) in the presence or absence of EGF, EGFR-antagonist (AG1478) or inhibitors of the downstream pathways PI3K (LY294002), mTOR (rapamycin) and MEK1 (PD98059). Biochemical activation of EGFR and the downstream markers Akt and ERK were examined by Western blot analysis. In absence of stimulation or inhibition, increasing doses of irradiation induced a dose-dependent enhancement of migrating cells (p < 0.05 for the 3 HNSCC cell lines) and a decrease of cell proliferation (p < 0.05 for the 3 HNSCC cell lines). The inhibition of EGFR or the downstream pathways reduced cell migration significantly (almost all p < 0.05 for the 3 HNSCC cell lines). Stimulation of HNSCC cells with EGF caused a significant increase in migration (p < 0.05 for the 3 HNSCC cell lines). After irradiation alone a pronounced activation of EGFR was observed by Western blot analysis. Our results demonstrate that the EGFR is involved in radiation induced migration of HNSCC cells. Therefore EGFR or the downstream pathways might be a target for the treatment of HNSCC to improve the efficacy of radiotherapy

Radiosensitization of head/neck squamous cell carcinoma by adenovirus-mediated expression of dominant negative constructs of the Nbs1 protein

International Nuclear Information System (INIS)

Carney, J.P.; Rhee, J.G.; Li, D.; Chen, T.; Suntharalingam, M.; O'Malley, B.W.

2001-01-01

Purpose: Local failure and toxicity to adjacent critical structures is a significant problem in radiation therapy of cancers of the head and neck. We are developing a gene therapy based method of sensitizing head/neck squamous cell carcinoma (HNSCC) to radiation treatment. As patients with the rare hereditary disorder, Nijmegen breakage syndrome show radiation sensitivity we hypothesized that tumor-specific disruption of the function of the Nbs1 protein would lead to enhanced cellular sensitivity to ionizing radiation. In order to test this hypothesis we have devised recombinant adenoviruses expressing various portions of the Nbs1 protein and assessed the ability of these viruses to increase the radiation sensitivity of HNSCC cells. Materials and Methods: We constructed two recombinant adenoviruses by cloning the full-length Nbs1 cDNA as well as the C-terminal 300 amino acids of Nbs1(Nbs1-300, aa453 to aa754) into an adenovirus backbone under the control of a CMV promoter. The resulting adenoviruses were used to infect HNSCC cell line 011. These cells were evaluated for expression of the viral based constructs and assayed for growth rate and clonogenic survival following radiation exposure. Results: A constitutively expressed GFP gene in the viral backbone confirmed efficient uptake of the virus into the 011 cell line and Western blot confirmed the presence of the virally expressed Nbs1 and Nbs1-300. Following exposure to ionizing radiation cells infected with the Nbs1-300 virus showed a significant reduction in growth rate relative to cells infected with control virus. Surprisingly, this effect was even stronger with the full-length wild-type Nbs1 protein. Examination of clonogenic survival also demonstrated statistically significant sensitization, however the effects of the two constructs were distinct as Nbs1-300 expression resulted in reduction of the shoulder while expression of the full-length Nbs1 showed a change in the slope of the survival curve

Radiosensitivity and effect of hypoxia in HPV positive head and neck cancer cells

International Nuclear Information System (INIS)

Sørensen, Brita Singers; Busk, Morten; Olthof, Nadine; Speel, Ernst-Jan; Horsman, Michael R.; Alsner, Jan; Overgaard, Jens

2013-01-01

Background and purpose: HPV associated Head and Neck Squamous Cell Carcinoma (HNSCC) represents a distinct subgroup of HNSCC characterized by a favorable prognosis and a distinct molecular biology. Previous data from the randomized DAHANCA 5 trial indicated that HPV positive tumors did not benefit from hypoxic modifications by Nimorazole during radiotherapy, whereas a significant benefit was observed in the HPV negative tumors. However, more studies have demonstrated equal frequencies of hypoxic tumors among HPV-positive and HPV-negative tumors. The aim of the present study was to determine radiosensitivity, the impact of hypoxia and the effect of Nimorazole in HPV positive and HPV negative cell lines. Materials and method: The used cell lines were: UDSCC2, UMSCC47 and UPCISCC90 (HPV positive) and FaDu DD , UTSCC33 and UTSCC5 (HPV negative). Cells were cultured under normoxic or hypoxic conditions, and gene expression levels of previously established hypoxia induced genes were assessed by qPCR. Cells were irradiated with various doses under normoxia, hypoxia or hypoxia +1 mM Nimorazole, and the clonogenic survival was determined. Results: The HPV positive and HPV negative cell lines exhibited similar patterns of upregulation of hypoxia induced genes in response to hypoxia. The HPV positive cell lines were up to 2.4 times more radiation sensitive than HPV negative cell lines. However, all HPV positive cells displayed the same response to hypoxia in radiosensitivity, with an OER in the range 2.3–2.9, and a sensitizer effect of Nimorazole of 1.13–1.29, similar to HPV negative cells. Conclusions: Although HPV positive cells had a markedly higher radiosensitivity compared to HPV negative cells, they displayed the same relative radioresistance under hypoxia and the same relative sensitizer effect of Nimorazole. The clinical observation that HPV positive patients do not seem to benefit from Nimorazole treatment is not due to inherent differences in hypoxia sensitivity

Directional dependency of air sampling

International Nuclear Information System (INIS)

1994-01-01

A field study was performed by Idaho State University-Environmental Monitoring Laboratory (EML) to examine the directional dependency of low-volume air samplers. A typical continuous low volume air sampler contains a sample head that is mounted on the sampler housing either horizontally through one of four walls or vertically on an exterior wall 'looking down or up.' In 1992, a field study was undertaken to estimate sampling error and to detect the directional effect of sampler head orientation. Approximately 1/2 mile downwind from a phosphate plant (continuous source of alpha activity), four samplers were positioned in identical orientation alongside one sampler configured with the sample head 'looking down'. At least five consecutive weekly samples were collected. The alpha activity, beta activity, and the Be-7 activity collected on the particulate filter were analyzed to determine sampling error. Four sample heads were than oriented to the four different horizontal directions. Samples were collected for at least five weeks. Analysis of the alpha data can show the effect of sampler orientation to a know near source term. Analysis of the beta and Be-7 activity shows the effect of sampler orientation to a ubiquitous source term

Vascular endothelial growth factor/bone morphogenetic protein-2 bone marrow combined modification of the mesenchymal stem cells to repair the avascular necrosis of the femoral head

Science.gov (United States)

Ma, Xiao-Wei; Cui, Da-Ping; Zhao, De-Wei

2015-01-01

Vascular endothelial cell growth factor (VEGF) combined with bone morphogenetic protein (BMP) was used to repair avascular necrosis of the femoral head, which can maintain the osteogenic phenotype of seed cells, and effectively secrete VEGF and BMP-2, and effectively promote blood vessel regeneration and contribute to formation and revascularization of tissue engineered bone tissues. To observe the therapeutic effect on the treatment of avascular necrosis of the femoral head by using bone marrow mesenchymal stem cells (BMSCs) modified by VEGF-165 and BMP-2 in vitro. The models were avascular necrosis of femoral head of rabbits on right leg. There groups were single core decompression group, core decompression + BMSCs group, core decompression + VEGF-165/BMP-2 transfect BMSCs group. Necrotic bone was cleared out under arthroscope. Arthroscopic observation demonstrated that necrotic bone was cleared out in each group, and fresh blood flowed out. Histomorphology determination showed that blood vessel number and new bone area in the repair region were significantly greater at various time points following transplantation in the core decompression + VEGF-165/BMP-2 transfect BMSCs group compared with single core decompression group and core decompression + BMSCs group (P < 0.05). These suggested that VEGF-165/BMP-2 gene transfection strengthened osteogenic effects of BMSCs, elevated number and quality of new bones and accelerated the repair of osteonecrosis of the femoral head. PMID:26629044

Direct reprogramming of somatic cells into neural stem cells or neurons for neurological disorders.

Science.gov (United States)

Hou, Shaoping; Lu, Paul

2016-01-01

Direct reprogramming of somatic cells into neurons or neural stem cells is one of the most important frontier fields in current neuroscience research. Without undergoing the pluripotency stage, induced neurons or induced neural stem cells are a safer and timelier manner resource in comparison to those derived from induced pluripotent stem cells. In this prospective, we review the recent advances in generation of induced neurons and induced neural stem cells in vitro and in vivo and their potential treatments of neurological disorders.

Direct microculture enzyme-linked immunosorbent assay for studying neural cells: oligodendrocytes.

Science.gov (United States)

Gard, A L; Warrington, A E; Pfeiffer, S E

1988-05-01

Oligodendrocyte development has been studied in a standardized primary microculture system initiated from day 20-21 fetal rat brain using a solid-phase enzyme-linked immunosorbent assay (ELISA) carried out directly on fixed cells (direct microculture ELISA). A highly reproducible dissociation procedure is described that allows careful control of the number of cells seeded per culture. At a seeding density of 1 x 10(5) cells/culture, up to 250 oligodendrocyte-generating microcultures consisting of 10-12% oligodendrocytes can be prepared from a single fetal rat brain, thereby permitting the simultaneous assay of multiple developmental parameters in sibling cultures. The validity of this method for quantifying myelinogenesis was established by comparing the results obtained by direct microculture ELISA with immunocytochemical counting of cells in parallel cultures. As few as 200 oligodendrocytes could be detected using a biotinylated anti-Ig and an avidin-urease conjugate detection system; CNP immunoreactivity measured by ELISA was linearly proportional to the number of immunolabeled cells between 6 and 34 days in culture; the developmental time courses of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) and myelin basic protein (MBP) expression determined by the two methods were very similar. Finally, cell suspensions were seeded at increasing dilution to determine the number of cells required to generate cultures that tested positive for oligodendrocytes by ELISA. As few as 9,000 cells were sufficient, predicting a minimum of 8,000 oligoprogenitors per 20-21 day fetal rat brain. The application of direct microculture ELISA for studying oligodendrocyte population size and myelinogenesis is discussed.

Heading in the right direction

Energy Technology Data Exchange (ETDEWEB)

Dutta, Ashok

2011-01-15

Statoil has developed a new directional technology which optimizes well positioning for unconsolidated geological formations, which addresses a crucial part for the implementation of a steam assisted gravity drainage (SAGD) program. This technology includes a rotary steerable system which, combined with an ultra-deep resistivity sensor, provides precise geosteering resulting therefore in in better well reservoir capture and characterization. Using this technique increases drilling efficiency, thus reducing the drilling time. The company's strategy is to provide cutting edge development to the oil sector and they have created a new research center in Calgary.

Establishment of a pig fibroblast-derived cell line for locus-directed transgene expression in cell cultures and blastocysts

DEFF Research Database (Denmark)

Jakobsen, Jannik E; Li, Juan; Moldt, Brian

2011-01-01

We report the establishment of a spontaneously immortalized pig cell line designated Pig Flip-in Visualize (PFV) for locus-directed transgene expression in pig cells and blastocysts. The PFV cell line was isolated from pig ear fibroblasts transfected with a Sleeping Beauty DNA transposon-based do......We report the establishment of a spontaneously immortalized pig cell line designated Pig Flip-in Visualize (PFV) for locus-directed transgene expression in pig cells and blastocysts. The PFV cell line was isolated from pig ear fibroblasts transfected with a Sleeping Beauty DNA transposon...

Direct Coal Oxidation in Modified Solid Oxide Fuel Cells

DEFF Research Database (Denmark)

Deleebeeck, Lisa; Gil, Vanesa; Ippolito, Davide

2015-01-01

Hybrid direct carbon fuel cells employ a classical solid oxide fuel cell together with carbon dispersed in a carbonate melt on the anode side. In a European project, the utilization of various coals has been investigated with and without addition of an oxidation catalyst to the carbon-carbonate s......Hybrid direct carbon fuel cells employ a classical solid oxide fuel cell together with carbon dispersed in a carbonate melt on the anode side. In a European project, the utilization of various coals has been investigated with and without addition of an oxidation catalyst to the carbon......-carbonate slurry or anode layer. The nature of the coal affects both open circuit voltage and power output. Highest OCV and power densities were observed for bituminous coal and by adding manganese oxide or praseodymium-doped ceria to the carbon/carbonate mixture. Comparing the carbon black fueled performance...... bituminous coal (73 mW/cm2). © 2015 ECS - The Electrochemical Society...

MRI in head trauma

International Nuclear Information System (INIS)

Hong, Jin Kyo

1986-01-01

In the diagnosis of head injury, Magnetic Resonance Imaging (MRI), like CT, is an effective method of distinguishing between intracerebral and extracerebral lesions. In our experience of MRI, early hematomas are almost isointense by Saturation Recovery (SR) method, so these must be performed with Spin Echo (SE) method for better visualization of hematomas. Isodense subdural hematomas, which is a diagnostic dilemma on CT images, are clearly seen on MRI. Delayed hematomas or residual parenchymal lesions are better demonstrated on MRI than on CT. Direct cornal, sagittal images and multiplanar facility of MRI provides excellent visualization of the the location and shape of extracerebral collection of hematoma. For the screening of head traumas, SE method is a technique of choice because of its excellent sensitivity within limited time.

MRI in head trauma

Energy Technology Data Exchange (ETDEWEB)

Hong, Jin Kyo [Shin Wha Hospital, Seoul (Korea, Republic of)

1986-02-15

In the diagnosis of head injury, Magnetic Resonance Imaging (MRI), like CT, is an effective method of distinguishing between intracerebral and extracerebral lesions. In our experience of MRI, early hematomas are almost isointense by Saturation Recovery (SR) method, so these must be performed with Spin Echo (SE) method for better visualization of hematomas. Isodense subdural hematomas, which is a diagnostic dilemma on CT images, are clearly seen on MRI. Delayed hematomas or residual parenchymal lesions are better demonstrated on MRI than on CT. Direct cornal, sagittal images and multiplanar facility of MRI provides excellent visualization of the the location and shape of extracerebral collection of hematoma. For the screening of head traumas, SE method is a technique of choice because of its excellent sensitivity within limited time.

Preoperative embolization of hypervascular head and neck tumours

International Nuclear Information System (INIS)

Gupta, A. K.; Purkayastha, S.; Bodhey, N. K.; Kapilamoorthy, T. R.; Kesavadas, C.

2007-01-01

Full text: The embolization of vascular tumours of the head and neck has become an important adjunct to the surgical treatment of these tumours. A vascular tumour in the head and neck region in a surgically treatable patient may be a candidate for embolization. Palliative embolization may be the sole treatment for high risk patients. Reducing intraoperative bleeding may shorten surgery time thus decreasing morbidity and mortality. The purpose of this study is to assess the efficacy of embolization as an adjunct to surgery or as a curative measure in the management of hypervascular head and neck tumours. We retrospectively reviewed the records of 46 consecutive patients 27 men and 16 women; mean age, 37.8 years) with 48 hypervascular head and neck tumours that had undergone preoperative transarterial, direct puncture or combined mode of embolization. Diagnosis of tumours was made on the basis of findings of imaging studies. The 46 patients underwent embolization either through transarterial route, by direct puncture technique or both direct puncture and arterial route. The devascularization reached 90-95% with the use of NBCA. The amount of devascularization reached by transarterial particle embolization is a little lesser. One patient (carotid body tumour) developed mild unilateral seventh, ninth and 10th cranial nerve palsy after transarterial embolization, transient hemiparesis was seen in another patient (nasopharyngeal angiofibroma). Both patients improved completely with steroids and had no deficit on follow up. One patient developed delayed glue migration into the middle cerebral artery territory 6 h after the procedure with no reported increase in size of the lesion in the following 5 years. Preoperative embolization of hypervascular tumour of head and neck region appears to be safe and improves the chance of complete removal during surgery with minimal blood loss

The role of stem cells in the prevention and treatment of radiation-induced xerostomia in patients with head and neck cancer.

Science.gov (United States)

Nevens, Daan; Nuyts, Sandra

2016-06-01

Xerostomia is an important complication following radiotherapy (RT) for head and neck cancer. Current treatment approaches are insufficient and can only temporarily relieve symptoms. New insights into the physiopathology of radiation-induced xerostomia might help us in this regard. This review discusses the current knowledge of salivary gland stem cells in radiation-induced xerostomia and their value in the prevention and treatment of this complication. Salivary gland stem cell transplantation, bone marrow-derived cell mobilization, molecular regulation of parotid stem cells, stem cell sparing RT, and adaptive RT are promising techniques that are discussed in this study. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells

DEFF Research Database (Denmark)

Czuchra, Aleksandra; Wu, Xunwei; Meyer, Hannelore

2005-01-01

of Cdc42 did not affect filopodium or lamellipodium formation and had no significant influence on the speed of directed migration nor on mitosis. Cdc42-deficient cells displayed a more elongated cell shape and had a reduced area. Furthermore, directionality during migration and reorientation of the Golgi...

Cilia in the head of hornets : Form and function

NARCIS (Netherlands)

Ishay, JS; Plotkin, M; Ermakov, N; Jongebloed, WL; Kalicharan, D; Bergman, DJ

2005-01-01

In the head of the Oriental hornet, beneath the cuticle, there are plaques of hair cells. These are distributed throughout the upper front part of the head; to wit: in the region of the vertex (i.e., around and behind the ocelli), in the genae around and behind the compound eyes (the ommatidia), and

Heads Up

Science.gov (United States)

... Connect with Us HEADS UP Apps Reshaping the Culture Around Concussion in Sports Get HEADS UP on Your Web Site Concussion ... HEADS UP on your web site! Create a culture of safety for young athletes Officials, learn how you can ... UP to Providers HEADS UP to Youth Sports HEADS UP to School Sports HEADS UP to ...

Long-term results of positron emission tomography-directed management of the neck in node-positive head and neck cancer after organ preservation therapy.

Science.gov (United States)

Sjövall, Johanna; Chua, Benjamin; Pryor, David; Burmeister, Elizabeth; Foote, Matthew C; Panizza, Benedict; Burmeister, Bryan H; Porceddu, Sandro V

2015-03-01

The current study presents the long-term results from a study designed to evaluate a restaging positron emission tomography (PET) directed policy whereby neck dissections were omitted in all node positive head and neck squamous cell carcinoma (N+HNSCC) patients with PET-negative lymph nodes after definitive radiotherapy (RT), with or without chemotherapy. A post-therapy nodal response assessment with PET and computed tomography (CT) was performed in patients who achieved a complete response at the primary site after definitive radiotherapy. Patients with PET-negative lymph nodes were observed regardless of residual CT abnormalities. One hundred and twelve patients, the majority of whom (83 patients, 74%) had oropharyngeal primaries, were treated on protocol. Median follow-up was 62months. Negative and positive predictive values for the restaging PET was 97.1% and 77.8% respectively, with only one patient who was PET-negative after treatment experiencing an isolated nodal relapse. PET-guided management of the neck following organ preservation therapy effectively spares neck dissections in patients with N+HNSCC without compromising isolated nodal control or overall survival. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Visual perception of axes of head rotation

Science.gov (United States)

Arnoldussen, D. M.; Goossens, J.; van den Berg, A. V.

2013-01-01

Registration of ego-motion is important to accurately navigate through space. Movements of the head and eye relative to space are registered through the vestibular system and optical flow, respectively. Here, we address three questions concerning the visual registration of self-rotation. (1) Eye-in-head movements provide a link between the motion signals received by sensors in the moving eye and sensors in the moving head. How are these signals combined into an ego-rotation percept? We combined optic flow of simulated forward and rotational motion of the eye with different levels of eye-in-head rotation for a stationary head. We dissociated simulated gaze rotation and head rotation by different levels of eye-in-head pursuit. We found that perceived rotation matches simulated head- not gaze-rotation. This rejects a model for perceived self-rotation that relies on the rotation of the gaze line. Rather, eye-in-head signals serve to transform the optic flow's rotation information, that specifies rotation of the scene relative to the eye, into a rotation relative to the head. This suggests that transformed visual self-rotation signals may combine with vestibular signals. (2) Do transformed visual self-rotation signals reflect the arrangement of the semi-circular canals (SCC)? Previously, we found sub-regions within MST and V6+ that respond to the speed of the simulated head rotation. Here, we re-analyzed those Blood oxygenated level-dependent (BOLD) signals for the presence of a spatial dissociation related to the axes of visually simulated head rotation, such as have been found in sub-cortical regions of various animals. Contrary, we found a rather uniform BOLD response to simulated rotation along the three SCC axes. (3) We investigated if subject's sensitivity to the direction of the head rotation axis shows SCC axes specifcity. We found that sensitivity to head rotation is rather uniformly distributed, suggesting that in human cortex, visuo-vestibular integration is

Visual perception of axes of head rotation

Directory of Open Access Journals (Sweden)

David Mattijs Arnoldussen

2013-02-01

Full Text Available Registration of ego-motion is important to accurately navigate through space. Movements of the head and eye relative to space are registered through the vestibular system and optical flow, respectively. Here, we address three questions concerning the visual registration of self-rotation. 1. Eye-in-head movements provide a link between the motion signals received by sensors in the moving eye and sensors in the moving head. How are these signals combined into an ego-rotation percept? We combined optic flow of simulated forward and rotational motion of the eye with different levels of eye-in-head rotation for a stationary head. We dissociated simulated gaze rotation and head rotation by different levels of eye-in-head pursuit.We found that perceived rotation matches simulated head- not gaze-rotation. This rejects a model for perceived self-rotation that relies on the rotation of the gaze line. Rather, eye-in-head signals serve to transform the optic flow’s rotation information, that specifies rotation of the scene relative to the eye, into a rotation relative to the head. This suggests that transformed visual self-rotation signals may combine with vestibular signals.2. Do transformed visual self-rotation signals reflect the arrangement of the semicircular canals (SCC? Previously, we found sub-regions within MST and V6+ that respond to the speed of the simulated head rotation. Here, we re-analyzed those BOLD signals for the presence of a spatial dissociation related to the axes of visually simulated head rotation, such as have been found in sub-cortical regions of various animals. Contrary, we found a rather uniform BOLD response to simulated rotation along the three SCC axes.3. We investigated if subject’s sensitivity to the direction of the head rotation axis shows SCC axes specifcity. We found that sensitivity to head rotation is rather uniformly distributed, suggesting that in human cortex, visuo-vestibular integration is not arranged into

In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Nestor, M.; Anniko, M.; Persson, M.; Dongen, G.A.M.S. van; Jensen, H.J.; Lundqvist, H.; Tolmachev, V.

2005-01-01

The purpose of this study was to analyse the properties of the astatinated chimeric MAb (cMAb) U36 as a conjugate to selectively target and eradicate head and neck squamous cell carcinoma (HNSCC). cMAb U36 was labelled with 211 At via the linker N-succinimidyl 4-(trimethylstannyl)benzoate (SPMB). The quality of the conjugate was extensively evaluated for binding and internalisation capacity, and compared with 125 I-SPMB-cMAb U36. The cellular toxicity of the astatinated conjugate was assessed in two types of in vitro growth assay and compared with 131 I-labelled cMAb U36 (directly labelled). Comparisons between 211 At-cMAb U36 and 125 I-cMAb U36 demonstrated an optimal functional capacity of the labelled products. Immunoreactivity and affinity assays showed high immunoreactive fractions (>93%), and an affinity in good agreement between the astatinated and iodinated antibodies. For both conjugates, specific binding to HNSCC cells could be demonstrated, as well as some internalisation. Retention of the astatinated conjugate was just slightly lower than for the iodinated conjugate and still reasonable for therapeutic use (31±2% vs 42.6±1.0% at 22 h), demonstrating no adverse effects from astatination of the antibody. Studies on cellular toxicity demonstrated a dose-dependent and antigen-specific cellular toxicity for 211 At-cMAb U36, with about 10% cell survival at 50 decays per cell. The 131 I-labelled conjugate was not as efficient, with a surviving cell fraction of about 50% at 55 decays per cell. (orig.)

Neck extensor muscle weakness (Dropped head syndrome) following radiotherapy

International Nuclear Information System (INIS)

Bhatia, S.; Miller, R.C.; Lachance, D.L.

2006-01-01

Background. Dropped head syndrome is an unusual condition in which the head cannot be held upright in its normal anatomic position secondary to pronounced, isolated, neck extensor muscle weakness. Case report. A case of dropped head syndrome in a female with a history of radiotherapy for Hodgkin's lymphoma and a clinical history consistent with multiple sclerosis is presented, and potential etiologies are discussed. Conclusions. Muscular atrophy and lower motor neuron injury secondary to isolated anterior horn cell injury from radiotherapy emerge as the most likely etiology. (author)

Acid sphingomyelinase activity as an indicator of the cell stress in HPV-positive and HPV-negative head and neck squamous cell carcinoma.

Science.gov (United States)

Gerle, Mirko; Medina, Tuula Peñate; Gülses, Aydin; Chu, Hanwen; Naujokat, Hendrik; Wiltfang, Jörg; Açil, Yahya

2018-03-21

Human papillomavirus (HPV) infection, especially HPV-16 and HPV-18, has been increasingly associated with head and neck squamous cell carcinoma. The treatment of HPV-positive squamous cell carcinoma has a better response to both radiotherapy and chemotherapy and presents a better prognosis for the patient. Defining the underlying mechanism of the difference might help in developing future treatment options and could be an important factor in personal therapy planning. Endogenously secreted acid sphingomyelinase (ASMase) levels in the cellular stress caused by irradiation and cisplatin were investigated. MTT assay was performed to evaluate the viability of the treated cells. Keratinocytes were used to evaluate the effects of radiation on normal tissues. Irradiation caused a dose-dependent increase in ASMase activity in both SCC9 HPV-negative, and UDSCC2 HPV-positive cells. ASMase activity in UDSCC2 cells was significantly higher than that in SCC9 cells. UDSCC cells were more sensitive to cisplatin treatment than SCC cells, and the dose-response in the activity was observed in long-time treatments when high doses of cisplatin were used. The results of the current study have clearly showed that HPV positivity should be considered as one of the determinative factors which should be considered when tumor treatments are planned. However, further studies are needed to determine the differences in cellular responses and pathways among HPV-negative and HPV-positive cells.

Human Papilloma Virus in Head and Neck Squamous Cell Cancer

Science.gov (United States)

Asvadi Kermani, I; Seifi, SH; Dolatkhah, R; Sakhinia, E; Dastgiri, S; Ebrahimi, A; Lotfy, A; Esmaeili, HA; G, Mohammadi; M, Naderpour; SH, Hajalipour; Haggi A, Asghari; M, Nadri

2012-01-01

Background Epidemiologic and molecular evidences have established a strong link between high risk types of Human Papilloma Virus and a subgroup of Head and Neck Squamous Cell Carcinomas (HNSCC). We evaluated the frequency of HPV positivity in HNSCC and its relationship to demographic and some risk factor variables in an open case- control study. Methods Fourteen recently diagnosed patients with squamous cell cancer of oropharynx, hypopharynx and larynx aged 18-50 years were examined from 2008-2010 in Tabriz, Iran. HPV DNA was extracted from paraffin-embedded blocks of each patient's sample for PCR evaluation. Saliva samples of 94 control cancer-free subjects were collected for DNA analysis. Multivariable logistic regression method was used to calculate odds ratio for case-control comparisons. Results High risk HPV was detected in 6(42.8%) patients, and 6(5.3%) control subjects which was statistically significant (p<0.0001). HPV-18 was the most frequent type both in the cases and controls. HPV-16 DNA was detected in two patients of the case group, but it was not detected in any of the controls. The relation between demographic and risk factor variables was not statistically significant. Conclusion HPV infection has a significant impact on HNSCC. Despite HPV-16 stronger impact, HPV-18 is more likely to cause malignant degeneration in such cancers amongst some communities. It is vital to introduce and conduct immunization schedules in health care systems to protect communities to some extent. PMID:25780535

Study on the micro direct ethanol fuel cell (Micro-DEFC) performance

Science.gov (United States)

Saisirirat, Penyarat; Joommanee, Bordindech

2018-01-01

The direct ethanol fuel cell (DEFC) is selected for this research. DEFC uses ethanol in the fuel cell instead of the more toxic methanol. Ethanol is more attractive than methanol by many reasons. Ethanol is a hydrogen-rich liquid and it has a higher specific energy (8.0 kWh/kg) compared to that of methanol (6.1 kWh/kg). Ethanol can be obtained in great quantity from biomass through a fermentation process from renewable resources such as sugar cane, wheat, corn, and even straw. The use of ethanol would also overcome both the storage and infrastructure challenge of hydrogen for fuel cell applications. The experimental apparatus on the micro direct ethanol fuel cell for measuring the cell performance has been set for this research. The objective is to study the micro direct ethanol fuel cell performance for applying with the portable electronic devices. The cell performance is specified in the terms of cell voltage, cell current and power of the cell at room operating temperature and 1 atm for the pressure and also includes the ethanol fuel consumption. The effect of operating temperature change on the electrical production performance is also studied. The steady-state time for collecting each data value is about 5-10 minutes. The results show that with the increase of concentrations of ethanol by volume, the reactant concentration at the reaction sites increases so the electrochemical rate also increases but when it reaches the saturated point the performance gradually drops.

SU-E-T-593: Clinical Evaluation of Direct Aperture Optimization in Head/Neck and Prostate IMRT Treatment

Energy Technology Data Exchange (ETDEWEB)

Hosini, M [King Saud University Hospitals, Riyadh (Saudi Arabia); GALAL, M [Hermitage Medical Clinic, Dublin (Ireland); Emam, I [Ain Shams University, Cairo (France); Kamal, G; Algohary, M [Al Azhar University, Cairo (Egypt)

2014-06-01

Purpose: To investigate the planning and dosimetric advantages of direct aperture optimization (DAO) over beam-let optimization in IMRT treatment of head and neck (H/N) and prostate cancers. Methods: Five Head and Neck as well as five prostate patients were planned using the beamlet optimizer in Elekta-Xio ver 4.6 IMRT treatment planning system. Based on our experience in beamlet IMRT optimization, PTVs in H/N plans were prescribed to 70 Gy delivered by 7 fields. While prostate PTVs were prescribed to 76 Gy with 9 fields. In all plans, fields were set to be equally spaced. All cases were re-planed using Direct Aperture optimizer in Prowess Panther ver 5.01 IMRT planning system at same configurations and dose constraints. Plans were evaluated according to ICRU criteria, number of segments, number of monitor units and planning time. Results: For H/N plans, the near maximum dose (D2) and the dose that covers 95% D95 of PTV has improved by 4% in DAO. For organs at risk (OAR), DAO reduced the volume covered by 30% (V30) in spinal cord, right parotid, and left parotid by 60%, 54%, and 53% respectively. This considerable dosimetric quality improvement achieved using 25% less planning time and lower number of segments and monitor units by 46% and 51% respectively. In DAO prostate plans, Both D2 and D95 for the PTV were improved by only 2%. The V30 of the right femur, left femur and bladder were improved by 35%, 15% and 3% respectively. On the contrary, the rectum V30 got even worse by 9%. However, number of monitor units, and number of segments decreased by 20% and 25% respectively. Moreover the planning time reduced significantly too. Conclusion: DAO introduces considerable advantages over the beamlet optimization in regards to organs at risk sparing. However, no significant improvement occurred in most studied PTVs.

Wild-type EGFR Is Stabilized by Direct Interaction with HSP90 in Cancer Cells and Tumors

Directory of Open Access Journals (Sweden)

Aarif Ahsan

2012-08-01

Full Text Available The epidermal growth factor receptor (EGFR has been targeted for inhibition using tyrosine kinase inhibitors and monoclonal antibodies, with improvement in outcome in subsets of patients with head and neck, lung, and colorectal carcinomas. We have previously found that EGFR stability plays a key role in cell survival after chemotherapy and radiotherapy. Heat shock protein 90 (HSP90 is known to stabilize mutant EGFR and ErbB2, but its role in cancers with wild-type (WT WT-EGFR is unclear. In this report, we demonstrate that fully mature, membrane-bound WT-EGFR interacts with HSP90 independent of ErbB2. Further, the HSP90 inhibitors geldanamycin (GA and AT13387 cause a decrease in WT-EGFR in cultured head and neck cancer cells. This decrease results from a significantly reduced half-life of WT-EGFR. WT-EGFR was also lost in head and neck xenograft specimens after treatment with AT13387 under conditions that inhibited tumor growth and prolonged survival of the mice. Our findings demonstrate that WT-EGFR is a client protein of HSP90 and that their interaction is critical for maintaining both the stability of the receptor as well as the growth of EGFR-dependent cancers. Furthermore, these findings support the search for specific agents that disrupt HSP90's ability to act as an EGFR chaperone.

Goniometer head

International Nuclear Information System (INIS)

Dzhazairov-Kakhramanov, V.; Berger, V.D.; Kadyrzhanov, K.K.; Zarifov, R.A.

1994-01-01

The goniometer head is an electromechanical instrument that performs the independent transfer of a testing sample on three coordinate axes (X, Y, Z) within limits of ±8 mm and independent rotation relative of these directions. The instrument comprises a sample holder, bellows component and three electrometer drives. The sample holder rotates around the axes X and Y, and is installed on the central arm which rotates around axis Z. One characteristic of this instrument is its independence which allows its use in any camera for researches in the field of radiation physics. 2 figs

The role of human papilloma virus and p16 in occult primary of the head and neck: a comprehensive review of the literature.

Science.gov (United States)

Fotopoulos, George; Pavlidis, Nicholas

2015-02-01

Cancer of unknown primary of the head and neck is a challenging entity for the oncologist. The role of human papilloma virus/p16 in carcinogenesis and in prognosis is well established in certain HNSCC especially in that of the oropharynx. In the case of occult primary of the head and neck the role of HPV/p16 positivity is not well defined regarding prognosis and localization of the primary. An independent review of PubMed and ScienceDirect database was performed up to May 2014 using combinations of terms such as "occult primary of the head and neck", "CUP of the head and neck" "metastatic cervical squamous cell carcinoma of unknown primary", "HPV" and "HPV and head and neck cancer". Literature review shows a strong association between HPV/p16 positivity and primary location in the oropharynx in patients with CUP of the head and neck as well as a better clinical outcome. HPV positivity and p16 overexpression could be used as surrogate markers in the search of the primary site of patients with CUP of the head and neck therefore maybe guiding treatment decisions. Copyright © 2014 Elsevier Ltd. All rights reserved.