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Gene Therapy AND Head and Neck

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https://www.readbyqxmd.com/read/28916527/demethylation-therapy-as-a-targeted-treatment-for-human-papilloma-virus-associated-head-and-neck-cancer
#1
Asel K Biktasova, Michael Hajek, Andrew B Sewell, Cyril S Gary, Gary Bellinger, Hari Deshpande, Aarti K Bhatia, Barbara A Burtness, Benjamin L Judson, Saral Mehra, Wendell G Yarbrough, Natalia Issaeva
PURPOSE: DNA methylation in human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) may have importance for continuous expression of HPV oncogenes, tumor cell proliferation and survival. Here, we determined activity of a global DNA demethylating agent, 5-azacytidine (5-aza), against HPV+ HNSCC in pre-clinical models and explored it as a targeted therapy in a window trial enrolling patients with HPV+ HNSCC. EXPERIMENTAL DESIGN: Sensitivity of HNSCC cells to 5-aza treatment was determined, then 5-aza activity was tested in vivo using xenografted tumors in a mouse model...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28903378/ago2-involves-the-malignant-phenotypes-and-fak-pi3k-akt-signaling-pathway-in-hypopharyngeal-derived-fadu-cells
#2
Yanhui Zhang, Baoxin Wang, Xinwei Chen, Weidong Li, Pin Dong
Argonaute 2 (AGO2) protein is usually overexpressed in various head and neck squamous cell carcinoma. However, the precise molecular mechanisms of AGO2 in hypopharyngeal cancer have not yet been clearly understood. Here we found the AGO2 expression in hypopharyngeal cancer tissues were generally higher comparing with that of the corresponding adjacent noncancerous epithelium tissues, and these were associated with the more aggressive clinicopathologic features and the poor clinical outcomes. Stable knockdown of AGO2 protein retarded cell proliferation, migration, invasion, arrested cell cycle and induced apoptosis...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902732/multimodality-radionuclide-imaging-in-a-patient-with-hereditary-paraganglioma-pheochromocytoma-syndrome
#3
So Y Yim, Valeria M Moncayo, Francisco J Pasquel, Raghuveer K Halkar
Hereditary paraganglioma (PGL)-pheochromocytoma (PCC) syndrome is a genetic disorder caused by a mutation of the tumor suppressor gene SDHD that results in a predisposition for head and neck PGLs and PCCs. We present a case of a 33-year-old woman where F-FDG PET/CT showed areas of increased uptake in both the adrenal and cervical regions, consistent with PCCs and PGLs, respectively. Further imaging revealed that PCCs were I-MIBG avid, whereas the PGLs were In-octreotide avid. This demonstrates the varying sensitivities of different imaging modalities in regard to neuroendocrine tumors and the potential for treatment using multiple targeted therapies...
September 11, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28881811/akt-can-modulate-the-in-vitro-response-of-hnscc-cells-to-irreversible-egfr-inhibitors
#4
Renato José Silva-Oliveira, Matias Melendez, Olga Martinho, Maicon F Zanon, Luciano de Souza Viana, André Lopes Carvalho, Rui Manuel Reis
Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877725/over-expression-of-bag-1-in-head-and-neck-squamous-cell-carcinomas-hnscc-is-associated-with-cisplatin-resistance
#5
Shutong Liu, Bo Ren, Hang Gao, Suchan Liao, Ying-Xian Zhai, Shirong Li, Xue-Jin Su, Ping Jin, David Stroncek, Zhixiang Xu, Qinghua Zeng, Yulin Li
BACKGROUND: In order to improve therapy for head and neck squamous cell carcinoma (HNSCC), biomarkers associated with local and/or distant tumor relapses and cancer drug resistance are urgently needed. This study identified a potential biomarker, Bcl-2 associated athanogene-1 (BAG-1), that is implicated in HNSCC insensitive to cisplatin and tumor progression. METHODS: Primary and advanced (relapsed from parental) University of Michigan squamous cell carcinoma cell lines were tested for sensitivity to cisplatin and gene expression profiles were compared between primary (cisplatin sensitive) and the relapsed (cisplatin resistant) cell lines by using Agilent microarrays...
September 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28866730/egfr-targeted-therapies-in-the-post-genomic-era
#6
Mary Jue Xu, Daniel E Johnson, Jennifer R Grandis
Over 90% of head and neck cancers overexpress the epidermal growth factor receptor (EGFR). In diverse tumor types, EGFR overexpression has been associated with poorer prognosis and outcomes. Therapies targeting EGFR include monoclonal antibodies, tyrosine kinase inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, and antisense gene therapy. Few EGFR-targeted therapeutics are approved for clinical use. The monoclonal antibody cetuximab is a Food and Drug Administration (FDA)-approved EGFR-targeted therapy, yet has exhibited modest benefit in clinical trials...
September 2, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28859688/a-13-gene-expression-based-radioresistance-score-highlights-the-heterogeneity-in-the-response-to-radiation-therapy-across-hpv-negative-hnscc-molecular-subtypes
#7
Jean-Philippe Foy, Louis Bazire, Sandra Ortiz-Cuaran, Sophie Deneuve, Janice Kielbassa, Emilie Thomas, Alain Viari, Alain Puisieux, Patrick Goudot, Chloé Bertolus, Nicolas Foray, Youlia Kirova, Pierre Verrelle, Pierre Saintigny
BACKGROUND: Radiotherapy for head and neck squamous cell carcinomas (HNSCC) is associated with a substantial morbidity and inconsistent efficacy. Human papillomavirus (HPV)-positive status is recognized as a marker of increased radiosensitivity. Our goal was to identify molecular markers associated with benefit to radiotherapy in patients with HPV-negative disease. METHODS: Gene expression profiles from public repositories were downloaded for data mining. Training sets included 421 HPV-negative HNSCC tumors from The Cancer Genome Atlas (TCGA) and 32 HNSCC cell lines with available radiosensitivity data (GSE79368)...
September 1, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28840431/cdna-microarray-analysis-of-human-keratinocytes-cells-of-patients-submitted-to-chemoradiotherapy-and-oral-photobiomodulation-therapy-pilot-study
#8
Heliton S Antunes, Gabriel Wajnberg, Marcos B Pinho, Natasha Andressa Nogueira Jorge, Joyce Luana Melo de Moraes, Claudio Gustavo Stefanoff, Daniel Herchenhorn, Carlos M M Araújo, Celia Maria Pais Viégas, Mariana P Rampini, Fernando L Dias, Patricia Savio de Araujo-Souza, Fabio Passetti, Carlos G Ferreira
Oral mucositis is an acute toxicity that occurs in patients submitted to chemoradiotherapy to treat head and neck squamous cell carcinoma. In this study, we evaluated differences in gene expression in the keratinocytes of the oral mucosa of patients treated with photobiomodulation therapy and tried to associate the molecular mechanisms with clinical findings. From June 2009 to December 2010, 27 patients were included in a randomized double-blind pilot study. Buccal smears from 13 patients were obtained at days 1 and 10 of chemoradiotherapy, and overall gene expression of samples from both dates were analyzed by complementary DNA (cDNA) microarray...
August 24, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28805796/bifidobacterium-breve-as-a-delivery-vector-of-il-24-gene-therapy-for-head-and-neck-squamous-cell-carcinoma-in-vivo
#9
L Wang, I Vuletic, D Deng, W Crielaard, Z Xie, K Zhou, J Zhang, H Sun, Q Ren, C Guo
Beneficial bacteria are becoming ever more popular gene delivery method for hypoxia- tumor targeting in vivo. In this study we investigated the therapeutic effect of new recombinant Bifidobacterium breve strain expressing IL-24 gene (B.breve-IL24) on head and neck tumor xenograft in mice. Briefly, B.breve transformants were obtained through electro-transformation. Bacteria-tumor targeting ability were analyzed in vivo over different time points (1, 3 and 7 days post- bacteria injection). Furthermore, the therapeutic effect of bacteria on tumor cells in vivo were analyzed as follows: 30 Balb/c nude mice bearing subcutaneous tumor were randomly divided in three groups (Drug group, GFP group and Saline group)...
August 14, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28783453/development-of-human-salivary-gland-like-tissue-in-vitro
#10
Marc Burghartz, Simon Lennartz, Matthias Schweinlin, Rudolf Hagen, Norbert Kleinsasser, Stephan Hackenberg, Gudrun Steußloff, Agmal Scherzad, Kathrin Radeloff, Christian Ginzkey, Heike Walles, Marco Metzger
The loss of salivary gland function caused by radiation therapy of the head and neck is a serious condition and it affects a patient's quality of life. The current lack of effective therapies demands new options to be explored. This study tested whether human salivary gland epithelial cells (SGECs) could be successfully cultured on a decellularized porcine gut matrix (SIS-muc) in both mono- and coculture with microvascular endothelial cells (mvECs). By performing immunofluorescence imaging, transmission as well as scanning electron microscopy (SEM), quantitative polymerase chain reaction (qPCR), and an amylase enzyme assay, it was investigated as to what extent the three-dimensional (3D)-cultured cells could maintain their molecular differentiation and the production of working α-amylase (α-AMY) compared with two-dimensional (2D) culture...
August 4, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28762750/genome-scale-modeling-of-nadph-driven-%C3%AE-lapachone-sensitization-in-head-and-neck-squamous-cell-carcinoma
#11
Joshua E Lewis, Francesco Costantini, Jade Mims, Xiaofei Chen, Cristina M Furdui, David A Boothman, Melissa L Kemp
AIMS: The purpose of this study was to investigate differential NADPH production between radiation-sensitive and -resistant head and neck squamous cell carcinoma (HNSCC) cell lines and whether these differences are predictive of sensitivity to the chemotherapeutic β-lapachone. RESULTS: We have developed a novel human genome-scale metabolic modeling platform that combines transcriptomic, kinetic, thermodynamic, and metabolite concentration data. Upon incorporation of this information into cell line-specific models, we observed that the radiation-resistant HNSCC model redistributed flux through several major NADPH-producing reactions...
September 14, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28756882/cell-genomics-and-immunosuppressive-biomarker-expression-influence-pd-l1-immunotherapy-treatment-responses-in-hnscc-a-computational-study
#12
Amber M Bates, Emily A Lanzel, Fang Qian, Taher Abbasi, Shireen Vali, Kim A Brogden
OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression is correlated with objective response rates to PD-1 and PD-L1 immunotherapies. However, both immunotherapies have only demonstrated 12%-24.8% objective response rates in patients with head and neck squamous cell carcinoma (HNSCC), demonstrating a need for a more accurate method to identify those who will respond before their therapy. Immunohistochemistry to detect PD-L1 reactivity in tumors can be challenging, and additional methods are needed to predict and confirm PD-L1 expression...
August 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28749946/genome-wide-association-analysis-identifies-genetic-correlates-of-immune-infiltrates-in-solid-tumors
#13
Nathan O Siemers, James L Holloway, Han Chang, Scott D Chasalow, Petra B Ross-MacDonald, Charles F Voliva, Joseph D Szustakowski
Therapeutic options for the treatment of an increasing variety of cancers have been expanded by the introduction of a new class of drugs, commonly referred to as checkpoint blocking agents, that target the host immune system to positively modulate anti-tumor immune response. Although efficacy of these agents has been linked to a pre-existing level of tumor immune infiltrate, it remains unclear why some patients exhibit deep and durable responses to these agents while others do not benefit. To examine the influence of tumor genetics on tumor immune state, we interrogated the relationship between somatic mutation and copy number alteration with infiltration levels of 7 immune cell types across 40 tumor cohorts in The Cancer Genome Atlas...
2017: PloS One
https://www.readbyqxmd.com/read/28749195/hippo-pathway-contributes-to-cisplatin-resistant-induced-emt-in-nasopharyngeal-carcinoma-cells
#14
Shuo Li, Xiaomeng Zhang, Rongkai Zhang, Zibin Liang, Wei Liao, Zhengde Du, Chunsheng Gao, Fei Liu, Yunping Fan, Haiyu Hong
Nasopharyngeal carcinoma (NPC) is a kind of head-neck malignant tumor derived from the nasopharyngeal epithelium and is mainly prevalent in Southern China and Southeast Asia countries. Cisplatin (DDP) provides the first-line therapeutic administration in NPC patients. However, chemoresistance has been a main barrier and caused bad treatment outcome in NPC therapy. To understand the molecular mechanism of acquired resistance to DDP, multiple methods were performed to examine the morphocytology and molecular changes in DDP-resistant NPC cells...
2017: Cell Cycle
https://www.readbyqxmd.com/read/28713931/downregulation-of-mirna-26b-inhibits-cancer-proliferation-of-laryngeal-carcinoma-through-autophagy-by-targeting-ulk2-and-inactivation-of-the-pten-akt-pathway
#15
Shujing Wang, Dandan Guo, Congying Li
Laryngeal carcinoma is one of the most common tumors of the head and neck cancers, the pathogenesis of which remains yet unclear. It has been discovered through research that microRNAs (miRNAs) play an important role during the genesis of laryngeal carcinoma. In the present study we investigated the effect of miRNA-26b on the proliferation of laryngeal carcinoma and elucidated the potential underlying mechanisms in order to provide new targets for laryngeal carcinoma. Firstly, we found that miRNA-26b expression was significantly increased in patients with laryngeal carcinoma, compared with normal volunteers...
July 11, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28712100/the-role-of-genomic-techniques-in-predicting-response-to-radiation-therapy
#16
REVIEW
Noelle L Williams, Tu Dan, Nicholas G Zaorsky, Shivank Garg, Robert B Den
The understanding of the relationship between genetic variation and an individual patient's response to radiation therapy (RT) has gained significant ground over the past several years. Genetic markers have been identified that could ultimately serve as the foundation for predictive models in clinical practice, and that hold the potential to revolutionize the delivery of precision medicine in oncology. Single nucleotide polymorphisms, single genes, and/or gene signatures could ultimately serve as the basis for patient stratification in prospective clinical trials...
July 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28678827/identifying-novel-genes-and-biological-processes-relevant-to-the-development-of-cancer-therapy-induced-mucositis-an-informative-gene-network-analysis
#17
Cielito C Reyes-Gibby, Stephanie C Melkonian, Jian Wang, Robert K Yu, Samuel A Shelburne, Charles Lu, Gary Brandon Gunn, Mark S Chambers, Ehab Y Hanna, Sai-Ching J Yeung, Sanjay Shete
Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis...
2017: PloS One
https://www.readbyqxmd.com/read/28671677/effects-of-proton-versus-photon-irradiation-on-lymph-angiogenic-inflammatory-proliferative-and-anti-tumor-immune-responses-in-head-and-neck-squamous-cell-carcinoma
#18
M Lupu-Plesu, A Claren, S Martial, P-D N'Diaye, K Lebrigand, N Pons, D Ambrosetti, I Peyrottes, J Feuillade, J Hérault, M Dufies, J Doyen, G Pagès
The proximity of organs at risk makes the treatment of head and neck squamous cell carcinoma (HNSCC) challenging by standard radiotherapy. The higher precision in tumor targeting of proton (P) therapy could promote it as the treatment of choice for HNSCC. Besides the physical advantage in dose deposition, few is known about the biological impact of P versus photons (X) in this setting. To investigate the comparative biological effects of P versus X radiation in HNSCC cells, we assessed the relative biological effectiveness (RBE), viability, proliferation and mRNA levels for genes involved in (lymph)angiogenesis, inflammation, proliferation and anti-tumor immunity...
July 3, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28659184/rerg-suppresses-cell-proliferation-migration-and-angiogenesis-through-erk-nf-%C3%AE%C2%BAb-signaling-pathway-in-nasopharyngeal-carcinoma
#19
Weilin Zhao, Ning Ma, Shumin Wang, Yingxi Mo, Zhe Zhang, Guangwu Huang, Kaoru Midorikawa, Yusuke Hiraku, Shinji Oikawa, Mariko Murata, Kazuhiko Takeuchi
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignancy of the head and neck that is prevalent in Southeast Asia and southern China. Recent studies in epigenetics suggest that DNA methylation plays a pivotal role in the onset and progression of cancer. Combining the methyl-DNA binding domain capture technique and cDNA microarray analysis, we identified a unique hypermethylated gene, RERG (Ras-like estrogen-regulated growth inhibitor), that was down-regulated in NPC tissues. RERG is a tumor suppressor gene that was first reported in breast cancer...
June 28, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28656254/microrna-150-targets-rho-associated-protein-kinase-1-to-inhibit-cell-proliferation-migration-and-invasion-in-papillary-thyroid-carcinoma
#20
Lixia Cheng, Ruixiu Zhou, Min Chen, Linan Feng, Hongyan Li
Thyroid cancer is the most prevalent malignant tumor of the endocrine organs and accounts for one third of all head and neck tumors. Dysregulation of microRNAs is well‑known to contribute to the development of various cancers, including papillary thyroid carcinoma (PTC), which accounts for 80‑90% of all thyroid cancer cases. The present study aimed to investigate the expression, functional roles of microRNA‑150 (miR‑150) and its direct target gene in PTC. miR‑150 expression in PTC tissues and cell lines was analyzed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
August 2017: Molecular Medicine Reports
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