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Gene Therapy AND Head and Neck

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https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/29082766/new-developments-and-clinical-transition-of-hyaluronic-acid-based-nanotherapeutics-for-treatment-of-cancer-reversing-multidrug-resistance-tumour-specific-targetability-and-improved-anticancer-efficacy
#6
Muhammad Hassan Safdar, Zahid Hussain, Mohammed A S Abourehab, Humna Hasan, Sajal Afzal, Hnin Ei Thu
This review aims to overview and critically analyses recent developments in achieving tumour-specific delivery of anticancer agents, maximizing anticancer efficacy, and mitigating tumour progression and off-target effects. Stemming from critical needs to develop target-specific delivery vehicles in cancer therapy, various hyaluronic acid (HA)-conjugated nanomedicines have been fabricated owing to their biocompatibility, safety, tumour-specific targetability of drugs and genes, and proficient interaction with cluster-determinant-44 (CD44) receptors over-expressed on the surface of tumour cells...
October 30, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29069302/mechanistic-overview-of-immune-checkpoints-to-support-the-rational-design-of-their-combinations-in-cancer-immunotherapy
#7
A Rotte, J Y Jin, V Lemaire
Checkpoint receptor blockers, known to act by blocking the pathways that inhibit immune cell activation and stimulate immune responses against tumor cells, have been immensely successful in the treatment of cancer. Among several checkpoint receptors of immune cells, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), T-cell immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin-3 (TIM-3) and lymphocyte activation gene 3 (LAG-3) are the most commonly targeted checkpoints for cancer immunotherapy...
October 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045513/dpyd-genotype-guided-dose-individualization-to-improve-patient-safety-of-fluoropyrimidine-therapy-call-for-a-drug-label-update
#8
L M Henricks, F L Opdam, J H Beijnen, A Cats, J H M Schellens
The fluoropyrimidine anticancer drugs, especially 5-fluorouracil (5-FU) and capecitabine, are frequently prescribed for several types of cancer, including breast, colorectal, head and neck and gastric cancer. In the current drug labels of 5-FU and capecitabine in the European Union and the United States of America no adaptive dosing strategies are incorporated for polymorphic metabolism of 5-FU.Although treatment with fluoropyrimidines is generally well tolerated, a major clinical limitation is that a proportion of the treated population experiences severe, sometimes life-threatening, fluoropyrimidine-related toxicity...
August 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29024069/functional-analysis-of-esm1-by-sirna-knockdown-in-primary-and-metastatic-head-and-neck-cancer-cells
#9
Onur Bender, Mehmet Gunduz, Sadik Cigdem, Omer Faruk Hatipoglu, Muradiye Acar, Mesut Kaya, Reidar Grenman, Esra Gunduz, Kadriye Serife Ugur
BACKGROUND: Genetic factors play a large role in cancer and thus there is a great desire to understand the effects of different genes in cancer and to also develop gene therapy for better treatments. Therefore, the development of alternative diagnosis and therapy modalities are of utmost importance. The aim of our study is to illuminate the role of ESM1 (endothelial cell specific molecule-1, also known as Endocan) in proliferation and migration of head and neck cancer, thus helping to pave the way for new treatment modalities and predictive biomarkers...
October 11, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28976121/strategies-used-in-the-clinical-trials-of-gene-therapy-for-cancer
#10
Thekkuttuparambil Ananthanarayanan Ajith
Advances in understanding and manipulating genes have set the stage for scientists to alter a person's genetic material to prevent or treat diseases. Over the past decade, somatic gene therapy has been increasingly applied in clinical trials where the genetic material (DNA and RNA) introduced into a person's cell. Mutation and inactivation of the tumor suppressor genes are the unified concept of the development of tumor in humans. Therefore, researchers have discovered potential of gene therapies in the treatment of cancer...
September 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/28916527/demethylation-therapy-as-a-targeted-treatment-for-human-papilloma-virus-associated-head-and-neck-cancer
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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 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
#17
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
#18
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
#19
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
#20
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
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