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Gene Therapy AND Head and Neck

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https://www.readbyqxmd.com/read/29351293/fibroblast-growth-factor-receptor-1-amplification-in-laryngeal-squamous-cell-carcinoma
#1
Jesus Monico, Brandon Miller, Luminita Rezeanu, Warren May, Donna C Sullivan
Fibroblast growth factor receptor 1 (FGFR1) has been noted to be amplified in a variety of squamous cell carcinomas (SCCa) of the head, neck, and lung and increased copy number (CN) is a predictor of poor outcomes. FGFR1 is a therapeutic target for lung SCCa and inhibition therapy is currently in clinical trials. Absolute quantification of FGFR1 from formalin fixed paraffin embedded (FFPE) tissue of laryngeal SCCa was examined in this retrospective study. A droplet digital polymerase chain reaction (ddPCR) was used for absolute quantitation of the FGFR1 gene CN...
2018: PloS One
https://www.readbyqxmd.com/read/29348488/interferon-alpha-enhances-the-antitumour-activity-of-egfr-targeted-therapies-by-upregulating-rig-i-in-head-and-neck-squamous-cell-carcinoma
#2
Hailong Ma, Shufang Jin, Wenyi Yang, Ge Zhou, Mei Zhao, Sijie Fang, Zhiyuan Zhang, Jingzhou Hu
BACKGROUND: The epidermal growth factor receptor (EGFR)-targeted therapies have been tested in the clinic as treatments for head and neck squamous cell carcinoma (HNSCC). Owing to intrinsic or acquired resistance, EGFR-targeted therapies often lead to a low response rate and treatment failure. Interferon-alpha (IFNα) is a chemosensitising agent and multi-functional cytokine with a tumour inhibitory effect. However, the synergic effect of IFNα and EGFR-targeted therapies (erlotinib and nimotuzumab) and their mechanisms in HNSCC remain unclear...
January 18, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29340084/crispr-cas9-hdr-system-enhances-aqp1-gene-expression
#3
Zhimin Wang, Yaohe Wang, Songling Wang, Li-Rong Zhang, Na Zhang, Zhenguo Cheng, Qingshi Liu, Kelly J Shields, Baoli Hu, Michael J Passineau
Ionizing radiation (IR) isthe primarytherapeutic tool to treat patients with cancerous lesions located in the head and neck. In many patients, IR results in irreversible and severe salivary gland dysfunction or xerostomia. Currently there are no effective treatment options to reduce the effects of xerostomia. More recently, salivary gland gene therapy utilizing the water-specific protein aquaporin 1 (AQP1) has been of great interest to potentially correct salivary dysfunction. In this study, we used CRISPR-Cas9 gene editing along with the endogenous promoter of AQP1 within theHEK293 and MDCK cell lines...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29338444/adp53-gendicine-12-years-in-clinic-the-first-approved-gene-therapy-product-for-cancer
#4
Wei-Wei Zhang, Jianglong Li, Dinggang Li, Jiliang Liu, Xiuqin Li, Wei Li, Xiaolong Xu, Michael J Zhang, Lois Chandler, Hong Lin, Aiguo Hu, Wei Xu, Dominic Man-Kit Lam
Gendicine (Recombinant Human p53 Adenovirus, AdRSV-p53), developed by Shenzhen SiBiono GeneTech Company, was approved by CFDA in 2003. It has been used in clinical oncology for 12 years since it entered the market in 2004. As the first-in-class product for cancer gene therapy, Gendicine met its expectation and demonstrated with ample clinical data that it is safe and effective for treating cancer. SiBiono manufactured 41 batches in compliant with CFDA QC/QA requirements. Total 169,571 vials (1.0x1012 vector particles per vial) were used in more than 50,000 patients, among them about 5,000 were international form over 50 nations outside China...
January 16, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29334764/development-of-gene-therapeutics-for-head-and-neck-cancer-in-china-from-bench-to-bedside
#5
Wei Guo, Hao Song
Head and neck cancer represents the seventh most common cancer worldwide. Multidisciplinary sequential treatment was performed in patients with head and neck cancer. However, there is an urgent need for a new treatment approach that can effectively improve the outcomes of head and neck cancer patients with advanced stage. Gene therapy is a rapidly evolving field with head and neck cancer. It has been proved a promising way to improve the efficacy of antitumor treatment. China is at the forefront in clinical trials and practice of gene therapies in the world...
January 15, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29312563/trkb-promotes-laryngeal-cancer-metastasis-via-activation-pi3k-akt-pathway
#6
Liang Jiang, Zhihai Wang, Chuan Liu, Zhitao Gong, Yucheng Yang, Houyong Kang, Yanshi Li, Guohua Hu
Objectives: The aim of our study was to investigate the role of TrkB pathway in tumor occurrence and development for in order to provide theoretical basis to laryngeal cancer therapy. Materials and methods: Biological characteristics of the cells were studied by migration tests and colony forming assay. Gene and protein expression analysis was performed by RT-PCR or western blot. in vivo experiments were conducted in syngeneic BALB/c mice. Results: Significant changes in protein and gene expression, including higher expression level of TrkB, were found in cells and laryngeal cancer specimens...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298797/development-and-validation-of-a-gene-signature-for-patients-with-head-and-neck-squamous-cell-carcinomas-treated-by-postoperative-radio-chemo-therapy
#7
Stefan Schmidt, Annett Linge, Alex Zwanenburg, Stefan Leger, Fabian Lohaus, Constanze Krenn, Steffen Appold, Volker Gudziol, Alexander Nowak, Clare von Neubeck, Ingeborg Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Hatice Bunea, Anca Ligia Grosu, Amir Abdollahi, Juergen Debus, Ute Ganswindt, Claus Belka, Steffi U Pigorsch, Stephanie Elisabeth Combs, David Mönnich, Daniel Zips, Gustavo B Baretton, Frank Buchholz, Michael Baumann, Mechthild Krause, Steffen Löck
PURPOSE: The aim of this study was to identify and independently validate a novel gene signature predicting loco-regional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C). EXPERIMENTAL DESIGN: Gene expression analyses were performed using nanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patients...
January 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29284791/cadherin-6-is-activated-by-epstein-barr-virus-lmp1-to-mediate-emt-and-metastasis-as-an-interplay-node-of-multiple-pathways-in-nasopharyngeal-carcinoma
#8
L-L Zuo, J Zhang, L-Z Liu, Q Zhou, S-J Du, S-Y Xin, Z-P Ning, J Yang, H-B Yu, W-X Yue, J Wang, F-X Zhu, G-Y Li, J-H Lu
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein-Barr virus (EBV) infection plays a fundamental role in NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in LMP1-positive NPC tissues, and was identified as a target of the epithelium-specific miR-203...
December 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/29284308/fighting-cancer-with-viruses-oncolytic-virus-therapy-in-china
#9
Ding Wei, Jing Xu, Xinyuan Liu, Zhi-Nan Chen, Huijie Bian
Oncolytic virus has the special property with selective infection of tumor cells, leading to oncolysis of cancer cells and minimal toxicity to normal tissues, which is administrated in cancer therapy called oncolytic virotherapy. As a biological agent, oncolytic virus could induce tumor cell lysis, local immunological reaction, and enhance systemic anti-tumor immunity. These immune stimulatory properties of oncolytic virus will provide enormous benefits to override cancer. Nowadays, a great variety of oncolytic viruses including genetically engineered and natural viruses have shown promise in preclinical models and clinical studies...
December 28, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29260979/hspa5-negatively-regulates-lysosomal-activity-through-ubiquitination-of-mul1-in-head-and-neck-cancer
#10
Sun-Yong Kim, Hyo Jeong Kim, Haeng-Jun Kim, Dae Ho Kim, Chul-Ho Kim, Jae Ho Han, Hyung Kwon Byeon, Keunho Lee
HSPA5/GRP78/BiP plays an important role in cell survival or tumor progression. For these reasons, HSPA5 is an emerging therapeutic target in cancer development. Here we report that HSPA5 contributes to head and neck cancer (HNC) survival via maintenance of lysosomal activity; however, a nonthermal plasma (NTP, considered as a next-generation cancer therapy)-treated solution (NTS) inhibits HNC progression through HSPA5-dependent alteration of lysosomal activity. HSPA5 prevents NTS-induced lysosome inhibition through lysosomal-related proteins or regulation of gene expression...
December 20, 2017: Autophagy
https://www.readbyqxmd.com/read/29259349/are-fusion-transcripts-in-relapsed-metastatic-head-and-neck-cancer-patients-predictive-of-response-to-anti-egfr-therapies
#11
Paolo Bossi, Marco Siano, Cristiana Bergamini, Maria Cossu Rocca, Andrea P Sponghini, Marco Giannoccaro, Luca Tonella, Alessandro Paoli, Edoardo Marchesi, Federica Perrone, Silvana Pilotti, Laura D Locati, Silvana Canevari, Lisa Licitra, Loris De Cecco
Prediction of benefit from combined chemotherapy and the antiepidermal growth factor receptor cetuximab is a not yet solved question in head and neck squamous cell carcinoma (HNSCC). In a selected series of 14 long progression-free survival (PFS) and 26 short PFS patients by whole gene and microRNA expression analysis, we developed a model potentially predictive of cetuximab sensitivity. To better decipher the "omics" profile of our patients, we detected transcript fusions by RNA-seq through a Pan-Cancer panel targeting 1385 cancer genes...
2017: Disease Markers
https://www.readbyqxmd.com/read/29243047/role-of-%C3%AE-catenin-in-cisplatin-resistance-relapse-and-prognosis-of-head-and-neck-squamous-cell-carcinoma
#12
Souvick Roy, Madhabananda Kar, Shomereeta Roy, Arka Saha, Swatishree Padhi, Birendranath Banerjee
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer in India with high incidence and rapid recurrence rates. Here, we aimed to investigate the role of β-catenin, a developmental pathway gene, in HNSCC therapy resistance, DNA damage response, recurrence and prognosis. METHODS: In total 80 HNSCC samples were included. Western blot, immunohistochemistry and qRT-PCR analyses were performed to assess β-catenin expression in the cut margin and tumor areas of each sample...
December 14, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29193651/platelet-facilitated-photothermal-therapy-of-head-and-neck-squamous-cell-carcinoma
#13
Lang Rao, Lin-Lin Bu, Liang Ma, Wenbiao Wang, Huiqin Liu, Da Wan, Jian-Feng Liu, Andrew Li, Shi-Shang Guo, Lu Zhang, Wen-Feng Zhang, Xing-Zhong Zhao, Zhi-Jun Sun, Wei Liu
Here, we present a platelet-facilitated photothermal tumor therapy (PLT-PTT) strategy, in which PLTs act as carriers for targeted delivery of photothermal agents to tumor tissues and enhance the PTT effect. Gold nanorods (AuNRs) were first loaded into PLTs by electroporation and the resulting AuNR-loaded PLTs (PLT-AuNRs) inherited long blood circulation and cancer targeting characteristics from PLTs and good photothermal property from AuNRs. Using a gene-knockout mouse model, we demonstrate that the administration of PLT-AuNRs and localizing laser irradiation could effectively inhibit the growth of head and neck squamous cell carcinoma (HNSCC)...
November 29, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29163177/assessment-of-pharmacogenomic-panel-assay-for-prediction-of-taxane-toxicities-preliminary-results
#14
Raffaele Di Francia, Luigi Atripaldi, Salvo Di Martino, Carla Fierro, Tommaso Muto, Anna Crispo, Sabrina Rossetti, Gaetano Facchini, Massimiliano Berretta
Backbone: Paclitaxel and docetaxel are the primary taxane anticancer drugs regularly used to treat, breast, gastric, ovarian, head/neck, lung, and genitourinary neoplasm. Suspension of taxane treatments compromising patient benefits is more frequently caused by peripheral neuropathy and allergy, than to tumor progression. Several strategies for preventing toxicity have been investigated so far. Recently, findings on the genetic variants associated with toxicity and resistance to taxane-based chemotherapy have been reported...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29156447/pd-1-blockade-in-advanced-nsclc-a-focus-on-pembrolizumab
#15
REVIEW
Solange Peters, Keith M Kerr, Rolf Stahel
Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers and is responsible for a large proportion of all cancer-related deaths. Current treatment options are inadequate, reflecting a substantial unmet clinical need. Increasing knowledge regarding the mechanisms and genetic aberrations underlying tumor development and growth has heralded a new era of therapy in oncology, moving away from indiscriminate cytotoxic chemotherapy toward more finely focused, targeted medicine. The development of small-molecule drugs and monoclonal antibodies directed toward specific components of dysfunctional molecular or immune pathways, and mutated genes specific to particular cancer types, is leading the field to more personalized and less toxic treatment options, many of which have demonstrated greater efficacy and survival benefits than their chemotherapeutic counterparts...
October 23, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#16
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29140271/molecular-targeted-therapies-for-epidermal-growth-factor-receptor-and-its-resistance-mechanisms
#17
REVIEW
Toshimitsu Yamaoka, Motoi Ohba, Tohru Ohmori
Cancer therapies targeting epidermal growth factor receptor (EGFR), such as small-molecule kinase inhibitors and monoclonal antibodies, have been developed as standard therapies for several cancers, such as non-small cell lung cancer, colorectal cancer, pancreatic cancer, breast cancer, and squamous cell carcinoma of the head and neck. Although these therapies can significantly prolong progression-free survival, curative effects are not often achieved because of intrinsic and/or acquired resistance. The resistance mechanisms to EGFR-targeted therapies can be categorized as resistant gene mutations, activation of alternative pathways, phenotypic transformation, and resistance to apoptotic cell death...
November 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29135982/sting-expression-and-response-to-treatment-with-sting-ligands-in-premalignant-and-malignant-disease
#18
Jason R Baird, Zipeng Feng, Hong D Xiao, David Friedman, Ben Cottam, Bernard A Fox, Gwen Kramer, Rom S Leidner, R Bryan Bell, Kristina H Young, Marka R Crittenden, Michael J Gough
Human papilloma virus positive (HPV+) tumors represent a large proportion of anal, vulvar, vaginal, cervical and head and neck squamous carcinomas (HNSCC) and late stage invasive disease is thought to originate from a premalignant state. Cyclic dinucleotides that activate STimulator of INterferon Genes (STING) have been shown to cause rapid regression of a range of advanced tumors. We aimed to investigate STING ligands as a novel treatment for papilloma. We tested therapies in a spontaneous mouse model of papilloma of the face and anogenital region that histologically resembles human HPV-associated papilloma...
2017: PloS One
https://www.readbyqxmd.com/read/29099287/pax5-gene-as-a-novel-methylation-marker-that-predicts-both-clinical-outcome-and-cisplatin-sensitivity-in-esophageal-squamous-cell-carcinoma
#19
Keisuke Kurimoto, Masamichi Hayashi, Rafael Guerrero-Preston, Masahiko Koike, Mitsuro Kanda, Sho Hirabayashi, Hiroshi Tanabe, Nao Takano, Naoki Iwata, Yukiko Niwa, Hideki Takami, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Goro Nakayama, Hiroyuki Sugimoto, Tsutomu Fujii, Michitaka Fujiwara, Yasuhiro Kodera
Therapeutic strategies for esophageal cancer largely depend on histopathological assessment. To select appropriate treatments for individual patients, we examined the background molecular characteristics of tumor malignancy and sensitivity to multidisciplinary therapy. Seventy-eight surgically-resected esophageal squamous cell carcinoma (ESCC) cases during 2001-2013 were examined. PAX5, a novel gene methylation marker in ESCC, was evaluated in the specimens, as methylation of this gene was identified as an extremely tumor-specific event in squamous cell carcinogenesis of head and neck...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29094075/genomics-and-advances-towards-precision-medicine-for-head-and-neck-squamous-cell-carcinoma
#20
REVIEW
Carter Van Waes, Omar Musbahi
Objective: To provide a review of emerging knowledge from genomics and related basic science, preclinical, and clinical precision medicine studies in head and neck squamous cell carcinoma (HNSCC). Data Sources: The Cancer Genome Atlas Network (TCGA) publications, PubMed-based literature review, and ClinicalTrials.gov. Review Methods: TCGA publications, PubMed, and ClinicalTrials.gov were queried for genomics and related basic science, preclinical, and developmental clinical precision medicine studies in HNSCC...
October 2017: Laryngoscope Investigative Otolaryngology
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