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Gene Therapy AND Head and Neck

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https://www.readbyqxmd.com/read/27924064/toward-the-use-of-precision-medicine-for-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#1
REVIEW
Wang Gong, Yandi Xiao, Zihao Wei, Yao Yuan, Min Qiu, Chongkui Sun, Xin Zeng, Xinhua Liang, Mingye Feng, Qianming Chen
Precision medicine is a new strategy that aims at preventing and treating human diseases by focusing on individual variations in people's genes, environment and lifestyle. Precision medicine has been used for cancer diagnosis and treatment and shows evident clinical efficacy. Rapid developments in molecular biology, genetics and sequencing technologies, as well as computational technology, has enabled the establishment of "big data", such as the Human Genome Project, which provides a basis for precision medicine...
December 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27914687/braf-nras-kit-tert-gnaq-gna11-mutation-profile-analysis-of-head-and-neck-mucosal-melanomas-a-study-of-42-cases
#2
Şule Öztürk Sari, İsmaİl Yilmaz, Orhun Çiğ Taşkin, Gİzem Narli, Fatma Şen, Şenol Çomoğlu, Pinar Firat, Bİlge Bİlgİç, Dİlek Yilmazbayhan, Yasemİn Özlük, Nesİmİ Büyükbabanİ
Head and neck mucosal melanoma (HNMuM), which occurs mostly in the sinonasal and oral cavity, constitutes less than 1% of all malignant melanomas. Treatment options fail to improve the prognosis of this aggressive tumour that has low overall survival rates. Thus, development of new targeted therapies is essential. Unfortunately, limited data exist regarding their molecular profile. BRAF, NRAS, KIT, TERT and GNAQ/GNA11 oncogene mutations were investigated in 42 HNMuMs (28 sinonasal, 13 oral, 1 nasopharyngeal)...
November 30, 2016: Pathology
https://www.readbyqxmd.com/read/27901488/cancer-associated-fibroblasts-promote-cancer-cell-growth-through-a-mir-7-rassf2-par-4-axis-in-the-tumor-microenvironment
#3
Zongze Shen, Xing Qin, Ming Yan, Rongrong Li, Gang Chen, Jianjun Zhang, Wantao Chen
Cancer-associated fibroblasts (CAFs), a major component of cancer stroma, play an important role in cancer progression but little is known about how CAFs affect tumorigenesis and development. MicroRNAs (miRNAs) are small non-coding RNAs that can negatively regulate target mRNA expression at post-transcriptional levels. In head and neck cancer (HNC), our analysis of miRNA arrays showed that miR-7, miR-196 and miR-335 were significantly up-regulated in CAFs when compared with their paired normal fibroblasts (NFs)...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27895714/early-detection-and-personalized-treatment-in-oral-cancer-the-impact-of-omics-approaches
#4
REVIEW
Ilda Patrícia Ribeiro, Leonor Barroso, Francisco Marques, Joana Barbosa Melo, Isabel Marques Carreira
BACKGROUND: Oral cancer is one of the most common malignant lesions of the head and neck. This cancer is an aggressive and lethal disease with no significant improvements in the overall survival in the last decades. Moreover, the incidence of oral HPV-positive tumors is rising, especially in young people. This oral neoplasm develops through numerous molecular imbalances that affect key genes and signaling pathways; however, the molecular mechanisms involved in the pathogenesis and progression of oral tumors are still to be fully determined...
2016: Molecular Cytogenetics
https://www.readbyqxmd.com/read/27867017/genomic-amplification-of-fanconi-anemia-complementation-group-a-fanca-in-head-and-neck-squamous-cell-carcinoma-hnscc-cellular-mechanisms-of-radioresistance-and-clinical-relevance
#5
Julia Hess, Kristian Unger, Michael Orth, Ulrike Schötz, Lars Schüttrumpf, Verena Zangen, Igor Gimenez-Aznar, Agata Michna, Ludmila Schneider, Ramona Stamp, Martin Selmansberger, Herbert Braselmann, Ludwig Hieber, Guido A Drexler, Sebastian Kuger, Diana Klein, Verena Jendrossek, Anna A Friedl, Claus Belka, Horst Zitzelsberger, Kirsten Lauber
Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance...
November 17, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27863405/identification-of-evolutionarily-conserved-dna-damage-response-genes-that-alter-sensitivity-to-cisplatin
#6
Anna V Gaponova, Alexander Y Deneka, Tim N Beck, Hanqing Liu, Gregory Andrianov, Anna S Nikonova, Emmanuelle Nicolas, Margret B Einarson, Erica A Golemis, Ilya G Serebriiskii
Ovarian, head and neck, and other cancers are commonly treated with cisplatin and other DNA damaging cytotoxic agents. Altered DNA damage response (DDR) contributes to resistance of these tumors to chemotherapies, some targeted therapies, and radiation. DDR involves multiple protein complexes and signaling pathways, some of which are evolutionarily ancient and involve protein orthologs conserved from yeast to humans. To identify new regulators of cisplatin-resistance in human tumors, we integrated high throughput and curated datasets describing yeast genes that regulate sensitivity to cisplatin and/or ionizing radiation...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27805805/mild-hyperthermia-induced-by-gold-nanorod-mediated-plasmonic-photothermal-therapy-enhances-transduction-and-replication-of-oncolytic-adenoviral-gene-delivery
#7
Bo-Kyeong Jung, Yeon Kyung Lee, Jinwoo Hong, Hamidreza Ghandehari, Chae-Ok Yun
Oncolytic adenovirus (Ad) is a promising candidate for cancer gene therapy. However, as a monotherapy it has shown insufficient therapeutic efficacy in clinical trials. In this work we demonstrate that gold nanorod (GNR)-mediated mild hyperthermia enhances the cellular uptake and consequent gene expression of oncolytic Ad to head and neck tumor cells. We examined the combination of oncolytic Ad expressing vascular endothelial growth factor (VEGF) promoter-targeted artificial transcriptional repressor zinc-finger protein and GNR-mediated mild hyperthermia to improve antitumor effect...
November 2, 2016: ACS Nano
https://www.readbyqxmd.com/read/27696595/copy-number-profiling-of-tumor-suppressor-genes-in-head-and-neck-cancer
#8
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
https://www.readbyqxmd.com/read/27681750/nicotinamide-phosphoribosyltransferase-upregulation-by-phenylephrine-reduces-radiation-injury-in-submandibular-gland
#9
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
https://www.readbyqxmd.com/read/27671334/axl-inhibition-suppresses-the-dna-damage-response-and-sensitizes-cells-to-parp-inhibition-in-multiple-cancers
#10
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
https://www.readbyqxmd.com/read/27665970/high-dose-irradiation-of-bone-chips-preserves-the-in-vitro-activity-of-bone-conditioned-medium
#11
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
https://www.readbyqxmd.com/read/27639430/prognostic-factors-and-survival-in-non-central-nervous-system-rhabdoid-tumors
#12
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
https://www.readbyqxmd.com/read/27638861/alkylating-agent-induced-nrf2-blocks-endoplasmic-reticulum-stress-mediated-apoptosis-via-control-of-glutathione-pools-and-protein-thiol-homeostasis
#13
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...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27603913/cancer-testis-antigens-expression-regulation-tumor-invasion-and-use-in-immunotherapy-of-cancers
#14
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
https://www.readbyqxmd.com/read/27589568/t-cell-abundance-in-blood-predicts-acute-organ-toxicity-in-chemoradiotherapy-for-head-and-neck-cancer
#15
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
https://www.readbyqxmd.com/read/27501229/genomic-alteration-in-head-and-neck-squamous-cell-carcinoma-hnscc-cell-lines-inferred-from-karyotyping-molecular-cytogenetics-and-array-comparative-genomic-hybridization
#16
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
https://www.readbyqxmd.com/read/27492854/overexpression-of-angiopoietin-2-promotes-the-formation-of-oral-squamous-cell-carcinoma-by-increasing-epithelial-mesenchymal-transition-induced-angiogenesis
#17
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
https://www.readbyqxmd.com/read/27489285/mage-c2-specific-tcrs-combined-with-epigenetic-drug-enhanced-antigenicity-yield-robust-and-tumor-selective-t-cell-responses
#18
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
https://www.readbyqxmd.com/read/27484725/co-expression-of-ing4-and-p53-enhances-hypopharyngeal-cancer-chemosensitivity-to-cisplatin-in%C3%A2-vivo
#19
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
https://www.readbyqxmd.com/read/27465548/dna-repair-pathways-to-regulate-response-to-chemoradiotherapy-in-patients-with-locally-advanced-head-and-neck-cancer
#20
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
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