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Gene Therapy AND Head and Neck

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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
#1
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
#2
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
#3
Joshua E Lewis, Francesco Costantini, Jade Mims, Xiaofei Chen, Cristina 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 ß-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...
August 1, 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
#4
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
#5
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
#6
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...
July 27, 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28650338/ifn-%C3%AE-related-mrna-profile-predicts-clinical-response-to-pd-1-blockade
#13
Mark Ayers, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Andrey Loboda, David R Kaufman, Andrew Albright, Jonathan D Cheng, S Peter Kang, Veena Shankaran, Sarina A Piha-Paul, Jennifer Yearley, Tanguy Y Seiwert, Antoni Ribas, Terrill K McClanahan
Programmed death-1-directed (PD-1-directed) immune checkpoint blockade results in durable antitumor activity in many advanced malignancies. Recent studies suggest that IFN-γ is a critical driver of programmed death ligand-1 (PD-L1) expression in cancer and host cells, and baseline intratumoral T cell infiltration may improve response likelihood to anti-PD-1 therapies, including pembrolizumab. However, whether quantifying T cell-inflamed microenvironment is a useful pan-tumor determinant of PD-1-directed therapy response has not been rigorously evaluated...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28643357/nut-carcinoma-in-children-and-adults-a-multicenter-retrospective-study
#14
Lauriane Lemelle, Gaëlle Pierron, Paul Fréneaux, Sophie Huybrechts, Alexandra Spiegel, Dominique Plantaz, Morbize Julieron, Sophie Dumoucel, Antoine Italiano, Fréderic Millot, Christophe Le Tourneau, Guy Leverger, Pascal Chastagner, Matthieu Carton, Daniel Orbach
BACKGROUND: Nuclear protein of the testis (NUT) carcinoma (formerly NUT midline carcinoma) is an aggressive tumor defined by the presence of NUT rearrangement with a poor prognosis. This rare cancer is underdiagnosed and poorly treated. OBJECTIVE: The primary objective of this study was to describe the clinical, radiologic, and biological features of NUT carcinoma. The secondary objective was to describe the various treatments and assess their efficacy. METHODS: This retrospective multicenter study was based on review of the medical records of children and adults with NUT carcinoma with specific rearrangement or positive anti-NUT nuclear staining (>50%)...
June 23, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28637013/akt-can-modulate-the-in-vitro-response-of-hnscc-cells-to-irreversible-egfr-inhibitors
#15
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...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623401/biomarkers-in-the-assessment-of-oral-mucositis-in-head-and-neck-cancer-patients-a-systematic-review-and-meta-analysis
#16
REVIEW
Ana Gabriela Costa Normando, Camila Lopes Rocha, Isabela Porto de Toledo, Paulo Tadeu de Souza Figueiredo, Paula Elaine Diniz Dos Reis, Graziela De Luca Canto, Eliete Neves Silva Guerra
PURPOSE: The aim of this study was to evaluate the capability of biomarkers to predict the risk of oral mucositis in head and neck cancer patients, as well as to assess the correlation between these biomarkers and the severity of mucositis. METHODS: The search was performed at LILACS, PubMed, Science Direct, Scopus, and Web of Science. A search of the gray literature was performed on Google Scholar, OpenGrey, and ProQuest. The methodological quality of the included studies was assessed using the Meta-Analysis of Statistics Assessment and Review Instrument (MAStARI) tool, and the evidence quality was assessed by the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system...
September 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28613101/targeting-igf1r-pathway-in-cancer-with-micrornas-how-close-are-we
#17
Arathy S Kumar, Suresh K Rayala, Ganesh Venkatraman
Cancer of the head and neck are the most common cancers in India and account for 30% of all cancers. At molecular level, it could be attributed to the over-expression of growth factors like IGF1-R, EGFR, VEGF-R and deregulation of cell cycle regulators and tumor suppressors. IGF1-R is an emerging target in head and neck cancer treatment, because of its reported role in tumor development, progression and metastasis. IGF1R targeted agents are in advanced stages of clinical development. Nevertheless, these agents suffer from several disadvantages including acquired resistance and toxic side effects...
June 14, 2017: RNA Biology
https://www.readbyqxmd.com/read/28612520/regulation-of-itga3-by-the-anti-tumor-mir-199-family-inhibits-cancer-cell-migration-and-invasion-in-head-and-neck-cancer
#18
Keiichi Koshizuka, Toyoyuki Hanazawa, Naoko Kikkawa, Takayuki Arai, Atsushi Okato, Akira Kurozumi, Mayuko Kato, Koji Katada, Yoshitaka Okamoto, Naohiko Seki
For patients with head and neck squamous cell carcinoma (HNSCC), survival rates have not improved due to local recurrence and distant metastasis. Current targeted molecular therapies do not substantially benefit HNSCC patients. Therefore, it is necessary to use advanced genomic approaches to elucidate the molecular mechanisms underlying the aggressiveness of HNSCC cells. Analysis of our microRNA (miRNA) expression signature by RNA sequencing showed that the miR-199 family (miR-199a-5p, miR-199a-3p, miR-199b-5p and miR-199b-3p) was significantly reduced in cancer tissues...
August 2017: Cancer Science
https://www.readbyqxmd.com/read/28602756/antrodia-cinnamomea-sensitizes-radio-chemo-therapy-of-cancer-stem-like-cells-by-modulating-microrna-expression
#19
Yu-Kai Su, Ping-Hsiao Shih, Wei-Hwa Lee, Oluwaseun Adebayo Bamodu, Alexander T H Wu, Chun-Chih Huang, Yew-Min Tzeng, Michael Hsiao, Chi-Tai Yeh, Chien-Min Lin
ETHNOPHARMACOLOGICAL RELEVANCE: The discovery of many tissue-specific cancer stem cells (CSCs) continues to attract scientific attention. These CSCs are considered to be associated with chemo- and radio-resistance, and consequently, failure of conventional anticancer therapies. The recent demonstration of several microRNAs as enhancers of tumorigenicity via modulation of epithelial-mesenchymal transition and cancer stemness, makes them putative novel therapeutic target in oncology. Antrodia cinnamomea is a Chinese traditional medicine with several biological functions including anti-inflammation, antioxidant, and cancer prevention...
June 8, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28592616/multicenter-phase-ii-study-of-panitumumab-in-platinum-pretreated-advanced-head-and-neck-squamous-cell-cancer
#20
Marco Siano, Francesca Molinari, Vittoria Martin, Nicolas Mach, Martin Früh, Stefania Freguia, Irene Corradino, Michele Ghielmini, Milo Frattini, Vittoria Espeli
LESSONS LEARNED: Panitumumab shows activity in terms of disease control rate and preventing disease progression but not for tumor shrinkage in head and neck squamous cell cancer for second-line treatment. Epidermal growth factor receptor (EGFR) copy number gain, a property of tumor cells that theoretically could identify patients more likely to experience disease response, was common among patients having disease control.Our trial, given the lower toxicity with an every-2-week schedule, provides guidance for future trials, for example, in combinations of immune therapies and anti-EGFR-antibodies...
July 2017: Oncologist
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