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Gene Therapy AND Head and Neck

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https://www.readbyqxmd.com/read/29771197/emerging-insights-into-wnt-%C3%AE-catenin-signaling-in-head-and-neck-cancer
#1
K A Alamoud, M A Kukuruzinska
Head and neck cancer presents primarily as head and neck squamous cell carcinoma (HNSCC), a debilitating malignancy fraught with high morbidity, poor survival rates, and limited treatment options. Mounting evidence indicates that the Wnt/β-catenin signaling pathway plays important roles in the pathobiology of HNSCC. Wnt/β-catenin signaling affects multiple cellular processes that endow cancer cells with the ability to maintain and expand immature stem-like phenotypes, proliferate, extend survival, and acquire aggressive characteristics by adopting mesenchymal traits...
June 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29768630/what-determines-mortality-in-malignant-pheochromocytoma-report-of-a-case-with-eighteen-year-survival-and-review-of-the-literature
#2
Matheus de Oliveira Andrade, Vinícius Santos da Cunha, Dayana Carla de Oliveira, Olívia Laquis de Moraes, Adriana Lofrano-Porto
Pheochromocytoma (PCC) is a tumor derived from adrenomedullary chromaffin cells. Prognosis of malignant PCC is generally poor due to local recurrence or metastasis. We aim to report a case of malignant PCC with 18-year survival and discuss which factors may be related to mortality and long-term survival in malignant pheochromocytoma. The patient, a 45-year-old man, reported sustained arterial hypertension with paroxysmal episodes of tachycardia, associated with head and neck burning sensation, and hand and foot tremors...
March 2018: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29747488/investigating-the-feasibility-of-targeted-next-generation-sequencing-to-guide-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#3
Sun Min Lim, Sang Hee Cho, In Gyu Hwang, Jae Woo Choi, Hyun Chang, Myung-Ju Ahn, Keon Uk Park, Ji-Won Kim, Yoon Ho Ko, Hee Kyung Ahn, Byoung Chul Cho, Byung-Ho Nam, Sang Hoon Chun, Ji Hyung Hong, Jung Hye Kwon, Jong Gwon Choi, Eun Joo Kang, Tak Yun, Keun-Wook Lee, Joo-Hang Kim, Jin Soo Kim, Hyun Woo Lee, Min Kyoung Kim, Dongmin Jung, Ji Eun Kim, Bhumsuk Keam, Hwan Jung Yun, Sangwoo Kim, Hye Ryun Kim
Purpose: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. Materials and Methods: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×...
May 9, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29743718/expressional-analysis-of-disease-relevant-signalling-pathways-in-primary-tumours-and-metastasis-of-head-and-neck-cancers
#4
Dorothee Goesswein, Negusse Habtemichael, Aslihan Gerhold-Ay, Johanna Mazur, Désirée Wünsch, Shirley K Knauer, Julian Künzel, Christoph Matthias, Sebastian Strieth, Roland H Stauber
Head and neck squamous cell carcinoma (HNSCC) often metastasize to lymph nodes resulting in poor prognosis for patients. Unfortunately, the underlying molecular mechanisms contributing to tumour aggressiveness, recurrences, and metastasis are still not fully understood. However, such knowledge is key to identify biomarkers and drug targets to improve prognosis and treatments. Consequently, we performed genome-wide expression profiling of 15 primary HNSSCs compared to corresponding lymph node metastases and non-malignant tissue of the same patient...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29741610/aff4-promotes-tumorigenesis-and-tumor-initiation-capacity-of-head-and-neck-squamous-cell-carcinoma-cells-by-regulating-sox2
#5
Peng Deng, Jiongke Wang, Xuefeng Zhang, Xingyu Wu, Ning Ji, Jing Li, Min Zhou, Lu Jiang, Xin Zeng, Qianming Chen
Super elongation complex (SEC) controls gene transcription by releasing Pol II from pausing. Previous studies have shown that dysfunction of SEC was associated with multiple human cancers, such as leukemia and breast cancer. However, the role of SEC in head and neck squamous cell carcinoma (HNSCC) development remains largely unknown. In this study, we found expression of AF4/FMR2 family member 4 (AFF4), the core component of SEC, was upregulated dramatically in HNSCC cell lines and tumor tissues. By using siRNA-mediated depletion and overexpression of AFF4, we demonstrated AFF4 promoted proliferation, migration and invasion of HNSCC cells...
May 8, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29735410/distinct-shifts-in-the-oral-microbiota-are-associated-with-the-progression-and-aggravation-of-mucositis-during-radiotherapy
#6
Jin Hou, HuiMin Zheng, Pan Li, HaiYue Liu, HongWei Zhou, XiaoJun Yang
BACKGROUND AND PURPOSE: Oral mucositis remains one of the most common complications of radiation therapy for patients with head and neck cancer. This study aimed to investigate the dynamic shifts in the oral mucosal microbiota and their association with the progression and aggravation of mucositis in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. MATERIALS AND METHODS: In this study, oropharyngeal mucosa of patients were examined regularly, and sampled longitudinally in eight stages of their radiation treatment program: before radiation, and then after 10, 20, 30, 40, 50, 60, and 70 Gy...
May 4, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29733909/radiosensitivity-of-lung-metastases-by-primary-histology-and-implications-for-stereotactic-body-radiation-therapy-using-the-genomically-adjusted-radiation-dose
#7
Kamran A Ahmed, Jacob G Scott, John A Arrington, Arash O Naghavi, G Daniel Grass, Bradford A Perez, Jimmy J Caudell, Anders E Berglund, Eric A Welsh, Steven A Eschrich, Thomas J Dilling, Javier F Torres-Roca
INTRODUCTION: We assessed the radiosensitivity of lung metastases based on primary histology using a validated gene signature and model lung metastases for the genomically adjusted radiation dose (GARD). METHODS: Tissue samples were identified from our prospective observational protocol. The radiosensitivity index (RSI) 10 gene assay was run on samples and calculated alongside GARD using the previously published algorithms. A cohort of 105 patients with 137 lung metastases treated with SBRT at our institution was used for clinical correlation...
May 4, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29719593/whole-exome-sequencing-identifies-mtor-and-keap1-as-potential-targets-for-radiosensitization-of-hnscc-cells-refractory-to-egfr-and-%C3%AE-1-integrin-inhibition
#8
Erik Klapproth, Ellen Dickreuter, Falk Zakrzewski, Michael Seifert, Andreas Petzold, Andreas Dahl, Evelin Schröck, Barbara Klink, Nils Cordes
Intrinsic and acquired resistances are major obstacles in cancer therapy. Genetic characterization is commonly used to identify predictive or prognostic biomarker signatures and potential cancer targets in samples from therapy-naïve patients. By far less common are such investigations to identify specific, predictive and/or prognostic gene signatures in patients or cancer cells refractory to a specific molecular-targeted intervention. This, however, might have a great value to foster the development of tailored, personalized cancer therapy...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719019/primary-cutaneous-cd4-small-medium-t-cell-lymphoproliferative-disorder-clinical-and-histopathologic-features-differential-diagnosis-and-treatment
#9
Alejandro A Gru, Mark R Wick, Mary Eid
Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder usually presents as a slow-growing and asymptomatic solitary lesion in the form of a nodule or tumor in the head and neck region. By definition, it is histologically characterized by small- to medium-sized CD4+ lymphocytes involving the dermis in a dense and either nodular or diffuse pattern. Epidermotropism should be absent or minimal. Tumor cells are accompanied by numerous reactive B cells, plasma cells, histiocytes, and eosinophils...
March 2018: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/29715290/exome-array-analysis-of-adverse-reactions-to-fluoropyrimidine-based-therapy-for-gastrointestinal-cancer
#10
Matthew Traylor, Jemma L Walker, Adele A Corrigan, Monica A Hernandez, Stephen J Newhouse, Amos A Folarin, Hamel Patel, Paul J Ross, Jeremy D Sanderson, James Spicer, Natalie J Prescott, Christopher G Mathew, Anthony M Marinaki, Cathryn M Lewis
Fluoropyrimidines, including 5-fluororacil (5FU) and its pro-drug Capecitabine, are the common treatment for colorectal, breast, neck and head cancers-either as monotherapy or in combination therapy. Adverse reactions (ADRs) to the treatment are common and often result in treatment discontinuation or dose reduction. Factors contributing to ADRs, including genetic variation, are poorly characterized. We performed exome array analysis to identify genetic variants that contribute to adverse reactions. Our final dataset consisted of 504 European ancestry individuals undergoing fluoropyrimidine-based therapy for gastrointestinal cancer...
2018: PloS One
https://www.readbyqxmd.com/read/29606027/effects-of-cisplatin-5-fluorouracil-combination-therapy-on-oxidative-stress-dna-damage-mitochondrial-apoptosis-and-death-receptor-signalling-in-retinal-pigment-epithelium-cells
#11
Hande Güçlü, Zeynep Banu Doganlar, Vuslat Pelitli Gürlü, Altan Özal, Ayten Dogan, Meryem Aysenur Turhan, Oguzhan Doganlar
Combination therapies of cisplatin with 5-FU (PF) are an effective solution and have been widely used for the treatment of various categories of cancer. including anal, gastrointestinal and oral cancer, as well as head and neck tumours. The effects of combined PF treatment on vital intracellular signalling pathways in nontargeted cells remain unclear. The aim of this study is to explain the possible mechanisms by which combined PF treatment results in retinal toxicity and to investigate the effects of PF on important vital signalling pathways in ARPE 19 retinal pigmented epithelial cells...
April 2, 2018: Cutaneous and Ocular Toxicology
https://www.readbyqxmd.com/read/29599409/functional-precision-medicine-identifies-novel-druggable-targets-and-therapeutic-options-in-head-and-neck-cancer
#12
Chang Xu, Olga Nikolova, Ryan S Basom, Ryan M Mitchell, Reid Shaw, Russell D Moser, Heuijoon Park, Kay E Gurley, Michael C Kao, Carlos L Green, Franz X Schaub, Robert L Diaz, Hallie A Swan, In S Jang, Justin Guinney, Vijayakrishna K Gadi, Adam A Margolin, Carla Grandori, Christopher J Kemp, Eduardo Méndez
Purpose: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with high mortality and a lack of targeted therapies. To identify and prioritize druggable targets, we performed genome analysis together with genome-scale siRNA and oncology drug profiling using low-passage tumor cells derived from a patient with treatment-resistant HPV-negative HNSCC. Experimental Design: A tumor cell culture was established and subjected to whole-exome sequencing, RNA sequencing, comparative genome hybridization, and high-throughput phenotyping with a siRNA library covering the druggable genome and an oncology drug library...
March 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29575240/role-of-p38-mapk-in-disease-relapse-and-therapeutic-resistance-by-maintenance-of-cancer-stem-cells-cscs-in-head-and-neck-squamous-cell-carcinoma
#13
Shomereeta Roy, Souvick Roy, Madhabananda Kar, Swatishree Padhi, Arka Saha, Kumari Anuja, Birendranath Banerjee
AIM: This study aims to investigate the role of p38 MAPK in maintenance of Cancer Stem Cell (CSC) phenotype, therapy resistance and DNA damage repair and response in Head and Neck Squamous Cell Carcinoma (HNSCC). METHODS: In this study 104 HNSCC patients were included. Western blot, immunohistochemistry and qPCR analysis were performed to investigate expression level of p-p38 and CSC markers in cut margin and tumor area of HNSCC patients. The expression level of p-p38 and CSC markers were also evaluated in HNSCC cells with or without p38 inhibitor...
March 25, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29566446/polymorphism-of-regulatory-region-of-ghrl-gene-2531c-t-as-a-promising-predictive-factor-for-radiotherapy-induced-oral-mucositis-in-patients-with-head-neck-cancer
#14
Anna Brzozowska, Iwona Homa-Mlak, Radosław Mlak, Paweł Gołębiowski, Marcin Mazurek, Marzanna Ciesielka, Teresa Małecka-Massalska
BACKGROUND: The purpose of this study was to investigate the relationship between single nucleotide polymorphisms (SNP; rs1629816) in the regulatory region (c.-2531C>T) of the ghrelin (GHRL) gene and the occurrence and severity of oral mucositis caused by radiotherapy (RT) in patients with head and neck cancer. METHODS: Oral mucositis in 65 patients with head and neck cancer who underwent irradiation were assessed according to Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) scale...
March 22, 2018: Head & Neck
https://www.readbyqxmd.com/read/29560384/neurturin-gene-therapy-protects-parasympathetic-function-to-prevent-irradiation-induced-murine-salivary-gland-hypofunction
#15
Joao N A Ferreira, Changyu Zheng, Isabelle M A Lombaert, Corinne M Goldsmith, Ana P Cotrim, Jennifer M Symonds, Vaishali N Patel, Matthew P Hoffman
Head and neck cancer patients treated with irradiation often present irreversible salivary gland hypofunction for which no conventional treatment exists. We recently showed that recombinant neurturin, a neurotrophic factor, improves epithelial regeneration of mouse salivary glands in ex vivo culture after irradiation by reducing apoptosis of parasympathetic neurons. Parasympathetic innervation is essential to maintain progenitor cells during gland development and for regeneration of adult glands. Here, we investigated whether a neurturin-expressing adenovirus could be used for gene therapy in vivo to protect parasympathetic neurons and prevent gland hypofunction after irradiation...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29541566/surgical-interventions-for-advanced-parameningeal-rhabdomyosarcoma-of-children-and-adolescents
#16
REVIEW
Paul J Choi, Joe Iwanaga, R Shane Tubbs, Emre Yilmaz
Owing to its rarity, rhabdomyosarcoma of the head and neck (HNRMS) has seldom been discussed in the literature. As most of the data is based only on the retrospective experiences of tertiary healthcare centers, there are difficulties in formulating a standard treatment protocol. Moreover, the disease is poorly understood at its pathological, genetic, and molecular levels. For instance, 20% of all histological assessment is inaccurate; even an experienced pathologist can confuse rhabdomyosarcoma (RMS) with neuroblastoma, Ewing's sarcoma, and lymphoma...
January 9, 2018: Curēus
https://www.readbyqxmd.com/read/29541413/combined-modality-radiation-therapy-promotes-tolerogenic-myeloid-cell-populations-and-stat3-related-gene-expression-in-head-and-neck-cancer-patients
#17
Sagus Sampath, Haejung Won, Erminia Massarelli, Min Li, Paul Frankel, Nayana Vora, Lalit Vora, Ellie Maghami, Marcin Kortylewski
Immunomodulation contributes to the antitumor efficacy of the fractionated radiation therapy (RT). Here, we describe immune effects of RT with concurrent systemic cisplatin or cetuximab treatment of patients with stage III-IV head and neck squamous cell carcinoma (HNSCC). Using longitudinally collected blood samples, we identified significant changes in cytokines/chemokines and immune cell populations compared to immune-related gene expression profiles in peripheral blood mononuclear cells (PBMCs). The 7-week combinatorial RT resulted in gradual elevation of proinflammatory mediators (IFNγ, IL-6, TNFɑ, CCL2), while levels of IL-12, cytokine essential for antitumor immune responses, were decreased...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29490660/identification-and-validation-a-tgf-%C3%AE-associated-long-non-coding-rna-of-head-and-neck-squamous-cell-carcinoma-by-bioinformatics-method
#18
Teng Huang, Wei Huang, Hong Lu, Bi-Yun Zhang, Jun Ma, Di Zhao, Yi-Jun Wang, Da-Hai Yu, Xia He
BACKGROUND: The role of transforming growth factorβ (TGF-β)-induced tumor progression in advanced malignancy is well established, but the involvement of long non-coding RNAs (lncRNAs) in TGF-β signaling remains unclear. This study aimed to identify TGF-β-associated lncRNAs in head and neck squamous cell carcinoma (HNSCC). METHODS: Expression profiling of lncRNAs was obtained using Gene Expression Omnibus and The Cancer Genome Atlas. Real-time quantitative PCR was used to analyze the expression of EPB41L4A-AS2 in HNSCC cell line...
February 28, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29489439/the-notch-pathway-in-head-and-neck-squamous-cell-carcinoma
#19
T Fukusumi, J A Califano
Comprehensive genomic analyses have been performed for head and neck squamous cell carcinoma (HNSCC), revealing a significant rate of NOTCH1 mutations and identifying NOTCH1 as the second most frequently mutated gene after TP53. Most NOTCH1 mutations are considered inactivating, indicating that NOTCH1 is a tumor suppressor gene. On the other hand, cohorts from Asian populations with HNSCC have shown activating NOTCH1 mutations. HNSCC with NOTCH1 mutations have a worse prognosis than the NOTCH1 wild-type tumors...
February 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29489434/targeting-the-dna-damage-response-in-oscc-with-tp53-mutations
#20
A Lindemann, H Takahashi, A A Patel, A A Osman, J N Myers
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer worldwide and in the United States. OSCC remains a major cause of morbidity and mortality in patients with head and neck cancers. Tobacco and alcohol consumption alone or with chewing betel nut are potential risk factors contributing to the high prevalence of OSCC. Multimodality therapies, including surgery, chemotherapy, biologic therapy, and radiotherapy, particularly intensity-modulated radiotherapy (IMRT), are the current treatments for OSCC patients...
February 1, 2018: Journal of Dental Research
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