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Gene Therapy AND Head and Neck

Zubeyde Yalniz, Semra Demokan, Burak Karabulut, Murat Ulusan, Yusufhan Suoglu, Nejat Dalay
BACKGROUND: Sensitive and reliable new biomarkers are needed in head and neck cancer to predict the outcome and for therapy that is more effective. Copy number alterations are frequent and play a critical role in cancer. METHODS: Copy number alterations of 24 tumor suppressor genes in head and neck cancer were analyzed simultaneously in matched tumor and normal samples from 93 patients using multiplex ligation-dependent probe amplification (MLPA). RESULTS: Chromosomes 3p and 9p displayed the most common alterations...
October 3, 2016: Head & Neck
Bin Xiang, Lichi Han, Xinyue Wang, Ling Tang, Kailiang Li, Xiuxiu Li, Xibo Zhao, Miaomiao Xia, Xixi Zhou, Fuyin Zhang, Ke Jian Liu
PURPOSE: Radiation therapy for head and neck cancer commonly leads to radiation sialadenitis. Emerging evidence has indicated that phenylephrine pretreatment reduces radiosensitivity in the salivary gland; however, the underlying cytoprotective mechanism remains unclear. Nicotinamide phosphoribosyltransferase (NAMPT) is not only a key enzyme for the nicotinamide adenine dinucleotide salvage pathway, but also a cytokine participating in cell survival, metabolism, and longevity, with a broad effect on cellular functions in physiology and pathology...
November 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Kavitha Balaji, Smruthi Vijayaraghavan, Lixia Diao, Pan Tong, Youhong Fan, Jason Pw Carey, Tuyen N Bui, Steven Warner, John V Heymach, Kelly K Hunt, Jing Wang, Lauren Averett Byers, Khandan Keyomarsi
: Epithelial to mesenchymal transition (EMT) is associated with a wide range of changes in cancer cells, including stemness, chemo- and radio-resistance and metastasis. The mechanistic role of upstream mediators of EMT has not yet been well characterized. Recently, we showed that non-small cell lung cancers (NSCLCs) that have undergone EMT overexpress AXL, a receptor tyrosine kinase. AXL is also overexpressed in a subset of triple-negative breast cancers (TNBCs) and head and neck squamous cell carcinomas (HNSCCs) and its overexpression has been associated with more aggressive tumor behavior and linked to resistance to chemotherapy, radiation, and targeted therapy...
September 26, 2016: Molecular Cancer Research: MCR
Kosaku Sawada, Richard J Miron, Dominic Leiser, Jordi Caballé-Serrano, Dieter D Bosshardt, Benoit Schaller, Daniel Buser, Reinhard Gruber
Extracorporeal irradiation sterilizes resected tumor bone used as autografts in reconstruction surgery. Therapeutic irradiation is a standard technique in head and neck cancer therapy that aims to preserve organ function. Bone irradiation has a complex, mostly inhibitory, effect on remodeling and regeneration, although the underlying mechanisms are still not fully understood. It remains unclear if extracorporeal irradiation affects the paracrine-like activity of the corresponding autografts. We recently reported that bone-conditioned medium from autogenous bone chips contains a number of factors that might affect cell activity...
2016: Journal of Oral Science
Benjamin A Farber, Neerav Shukla, Irene Isabel P Lim, Jennifer M Murphy, Michael P La Quaglia
INTRODUCTION: Non-central nervous system (non-CNS) rhabdoid tumors tend to present at a young age and have an extremely aggressive course, with dismal overall survival rates. Inactivation of the tumor suppressor gene SMARCB1 has been shown in rhabdoid tumors regardless of anatomic location, suggesting a common genetic basis. We retrospectively analyzed our institutional experience with non-CNS rhabdoid tumors to determine overall survival and prognostic variables. METHODS: We reviewed records of pediatric patients (age<22y) with non-CNS rhabdoid tumor at our institution between 1980 and 2014...
August 31, 2016: Journal of Pediatric Surgery
Alfeu Zanotto-Filho, V Pragathi Masamsetti, Eva Loranc, Sonal S Tonapi, Aparna Gorthi, Xavier Bernard, Rosângela Mayer Gonçalves, José C F Moreira, Yidong Chen, Alexander J R Bishop
Alkylating agents are a commonly used cytotoxic class of anticancer drugs. Understanding the mechanisms whereby cells respond to these drugs is key to identify means to improve therapy while reducing toxicity. By integrating genome-wide gene expression profiling, protein analysis and functional cell validation, we herein demonstrated a direct relationship between NRF2 and Endoplasmic Reticulum (ER) stress pathways in response to alkylating agents, which is coordinated by the availability of glutathione (GSH) pools...
September 16, 2016: Molecular Cancer Therapeutics
Arash Salmaninejad, Mohammad Reza Zamani, Mehrnaz Pourvahedi, Zahra Golchehre, Ali Hosseini Bereshneh, Nima Rezaei
UNLABELLED: Cancer/testis antigens (CTAs) are named based on their expression pattern that is restricted in a number of normal and abnormal tissues. Tumor cells frequently express antigens whose expression is typically restricted to germ cells. Their unique expression pattern is guaranteed by precise epigenetic regulatory mechanisms. Because of their tumor-limited, high immunogenicity, and biased expression, discovery of these molecules provides unprecedented opportunities for further research and clinical development in the field of cancer diagnosis and immunotherapy...
October 2016: Immunological Investigations
L Milena Beschel, Martin Leu, Sybille D Reichardt, Margret Rave-Fränk, Markus A Schirmer, Christine Stadelmann, Martin Canis, Hendrik A Wolff, Holger M Reichardt
Treatment of head and neck squamous cell carcinoma (HNSCC) by chemoradiotherapy (CRT) often results in high-grade acute organ toxicity (HGAOT). As these adverse effects impair the patients' quality of life and the feasibility of the planned therapy, we sought to analyze immunological parameters in tumor material and blood samples obtained from 48 HNSCC patients in order to assess the potential to predict the individual acute organ toxicity. T cells in the tumor stroma were enriched in patients developing HGAOT whereas levels of soluble factors in the plasma and gene expression in whole blood did not coincide with the occurrence of acute organ toxicity...
August 29, 2016: Oncotarget
Worapong Singchat, Ekarat Hitakomate, Budsaba Rerkarmnuaychoke, Aorarat Suntronpong, Beiyuan Fu, Winai Bodhisuwan, Surin Peyachoknagul, Fengtang Yang, Sittichai Koontongkaew, Kornsorn Srikulnath
Genomic alteration in head and neck squamous cell carcinoma (HNSCC) was studied in two cell line pairs (HN30-HN31 and HN4-HN12) using conventional C-banding, multiplex fluorescence in situ hybridization (M-FISH), and array comparative genomic hybridization (array CGH). HN30 and HN4 were derived from primary lesions in the pharynx and base of tongue, respectively, and HN31 and HN12 were derived from lymph-node metastatic lesions belonging to the same patients. Gain of chromosome 1, 7, and 11 were shared in almost all cell lines...
2016: PloS One
C Li, Q Li, Y Cai, Y He, X Lan, W Wang, J Liu, S Wang, G Zhu, J Fan, Y Zhou, R Sun
Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck and is associated with a high rate of lymph node metastasis. The initial step in the metastasis and transition of tumors is epithelial-mesenchymal transition (EMT)-induced angiogenesis, which can be mediated by angiopoietin 2 (ANG2), a key regulatory factor in angiogenesis. In the present study, immunohistochemistry and real-time quantitative reverse transcriptase (qRT-PCR) were used to measure the expression of ANG2 in OSCC tissues...
September 2016: Cancer Gene Therapy
Andre Kunert, Mandy van Brakel, Sabine van Steenbergen-Langeveld, Marvin da Silva, Pierre G Coulie, Cor Lamers, Stefan Sleijfer, Reno Debets
Adoptive T cell therapy has shown significant clinical success for patients with advanced melanoma and other tumors. Further development of T cell therapy requires improved strategies to select effective, yet nonself-reactive, TCRs. In this study, we isolated 10 TCR sequences against four MAGE-C2 (MC2) epitopes from melanoma patients who showed clinical responses following vaccination that were accompanied by significant frequencies of anti-MC2 CD8 T cells in blood and tumor without apparent side effects. We introduced these TCRs into T cells, pretreated tumor cells of different histological origins with the epigenetic drugs azacytidine and valproate, and tested tumor and self-reactivities of these TCRs...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Xin Ren, Hao Liu, Mingjie Zhang, Mengjun Wang, Shiyin Ma
Hypopharyngeal cancer is a distinct type of malignant head and neck tumor, which exhibits low sensitivity to anti-cancer drugs. The importance of developing methods for reducing chemotherapy resistance, and improving and enhancing prognosis has previously been emphasized and is considered a challenge for effective clinical treatment of hypopharyngeal cancer. The current study investigated the effects of co‑expression of inhibitor of growth protein 4 (ING4) and P53, a tumor suppressor gene, on chemosensitivity to cisplatin in human hypopharyngeal cancer xenografts in vivo, and the potential molecular mechanisms involved...
September 2016: Molecular Medicine Reports
B Cirauqui, M Margelí, V Quiroga, A Quer, N Karachaliou, I Chaib, J L Ramírez, A Muñoz, C Pollán, I Planas, A Drozdowsky, R Rosell
Platinum-based chemoradiotherapy (CRT) is a preferred standard of care for locally advanced head and neck cancer (HNC). However, survival benefit is small, with substantial toxicity and biomarkers of CRT resistance that could guide treatment selection and spare morbidity. Increased DNA repair in solid tumors may contribute to cancer cells' ability to survive in genotoxic stress environments afforded by therapy. We assessed mRNA expression levels of DNA repair-related genes BRCA1, RAP80, 53 binding protein 1 (53BP1), mediator of DNA damage checkpoint 1 (MDC1), and RNF8...
July 27, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Elena Illiano, Olivia Costantina Demurtas, Silvia Massa, Paola Di Bonito, Valerio Consalvi, Roberta Chiaraluce, Carlo Zanotto, Carlo De Giuli Morghen, Antonia Radaelli, Aldo Venuti, Rosella Franconi
BACKGROUND: High-risk human papillomaviruses (HR-HPVs) types 16 and 18 are the main etiological agents of cervical cancer, with more than 550,000 new cases each year worldwide. HPVs are also associated with other ano-genital and head-and-neck tumors. The HR-HPV E6 and E7 oncoproteins are responsible for onset and maintenance of the cell transformation state, and they represent appropriate targets for development of diagnostic and therapeutic tools. METHODS: The unmutated E6 gene from HPV16 and HPV18 and from low-risk HPV11 was cloned in a prokaryotic expression vector for expression of the Histidine-tagged E6 protein (His6-E6), according to a novel procedure...
2016: Journal of Translational Medicine
Luc G T Morris, Raghu Chandramohan, Lyndsay West, Ahmet Zehir, Debyani Chakravarty, David G Pfister, Richard J Wong, Nancy Y Lee, Eric J Sherman, Shrujal S Baxi, Ian Ganly, Bhuvanesh Singh, Jatin P Shah, Ashok R Shaha, Jay O Boyle, Snehal G Patel, Benjamin R Roman, Christopher A Barker, Sean M McBride, Timothy A Chan, Snjezana Dogan, David M Hyman, Michael F Berger, David B Solit, Nadeem Riaz, Alan L Ho
Importance: Recurrent and/or metastatic head and neck cancer is usually incurable. Implementation of precision oncology for these patients has been limited by incomplete understanding of the molecular alterations underlying advanced disease. At the same time, the molecular profiles of many rare head and neck cancer types are unknown. These significant gaps in knowledge need to be addressed to rationally devise new therapies. Objective: To illuminate the distinct biology of recurrent and metastatic head and neck cancers and review implementation of precision oncology for patients with advanced disease...
July 21, 2016: JAMA Oncology
Kosaku Sawada, Masako Fujioka-Kobayashi, Eizaburo Kobayashi, Jens O Brömme, Benoit Schaller, Richard J Miron
BACKGROUND: High dose radiation therapy is commonly used in maxillofacial surgeries to treat a number of head and neck tumors. Despite its widespread use, little information is available regarding the effects of irradiation on bone cell viability and release of growth factors following dose-dependent irradiation. METHODS: Bone samples were collected from porcine mandibular cortical bone and irradiated at doses of 0, 7.5, 15, 30, 60 and 120 Grays. Thereafter, cell viability was quantified, and the release of growth factors including TGFβ1, BMP2, VEGF, IL1β and RANKL were investigated over time...
2016: BMC Oral Health
Nijiro Nohata, Martin C Abba, J Silvio Gutkind
OBJECTIVES: The role of long non-coding RNA (lncRNA) expression in human head and neck squamous cell carcinoma (HNSCC) is still poorly understood. In this study, we aimed at establishing the onco-lncRNAome profiling of HNSCC and to identify lncRNAs correlating with prognosis and patient survival. MATERIALS AND METHODS: The Atlas of Noncoding RNAs in Cancer (TANRIC) database was employed to retrieve the lncRNA expression information generated from The Cancer Genome Atlas (TCGA) HNSCC RNA-sequencing data...
August 2016: Oral Oncology
Orsolya Rusz, Margit Pál, Éva Szilágyi, László Rovó, Zoltán Varga, Bernadett Tomisa, Gabriella Fábián, Levente Kovács, Olga Nagy, Petra Mózes, Zita Reisz, László Tiszlavicz, Péter Deák, Zsuzsanna Kahán
DNA damage response failure may influence the efficacy of DNA-damaging treatments. We determined the expression of 16 genes involved in distinct DNA damage response pathways, in association with the response to standard therapy. Twenty patients with locoregionally advanced, squamous cell head and neck carcinoma were enrolled. The treatment included induction chemotherapy (iChT) with docetaxel, cisplatin and 5-fluorouracil followed by concomitant chemoradiotherapy (ChRT) or radiotherapy (RT) alone. The volumetric metabolic therapeutic response was determined by [18F]FDG-PET/CT...
July 13, 2016: Pathology Oncology Research: POR
C Daly, C Castanaro, W Zhang, Q Zhang, Y Wei, M Ni, T M Young, L Zhang, E Burova, G Thurston
The epidermal growth factor receptor (EGFR) is a clinically validated target in head and neck squamous cell carcinoma (HNSCC), where EGFR-blocking antibodies are approved for first-line treatment. However, as with other targeted therapies, intrinsic/acquired resistance mechanisms limit efficacy. In the FaDu HNSCC xenograft model, we show that combined blockade of EGFR and ERBB3 promotes rapid tumor regression, followed by the eventual outgrowth of resistant cells. RNA sequencing revealed that resistant cells express FGFR3-TACC3 fusion proteins, which were validated as drivers of the resistant phenotype by several approaches, including CRISPR-mediated inactivation of FGFR3-TACC3 fusion genes...
June 27, 2016: Oncogene
Vishnu Modur, Pooja Joshi, Daotai Nie, K Thomas Robbins, Aziz U Khan, Krishna Rao
Platinum-based therapy is most often used to treat advanced cases of head and neck cancers, but only a small fraction of the patient population responds to cisplatin, with a median survival time of less than a year. Although gene signatures and molecular etiology of head and neck cancers have been previously described, none of them are predictive indicators of cisplatin treatment response in particular. Therefore, currently, there is a lack of clinically employable predictive indicators of the disease beyond HPV status to specifically predict patients' response to platinum-based therapy...
2016: PloS One
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