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Gene Therapy AND Head and Neck

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https://www.readbyqxmd.com/read/28192747/biology-and-patterns-of-response-to-egfr-inhibition-in-squamous-cell-cancers-of-the-lung-and-head-neck
#1
REVIEW
Rosalyn A Juergens, Scott V Bratman, Ming-Sound Tsao, Scott A Laurie, M Sara Kuruvilla, Albiruni R A Razak, Aaron R Hansen
The identification of common molecular aberrations that drive cancer progression has led to targeted therapies that improve treatment efficacy in many tumor types. Epidermal growth factor receptor (EGFR) inhibitors have been used to treat both lung and head and neck cancers with squamous cell histology. These tumors often show high EGFR expression and/or increased gene copy number, but low incidence of the activating kinase domain mutations common to adenocarcinomas of the lung. In this manuscript, we review clinical trial data on EGFR-inhibitors in the treatment of squamous cell carcinoma (SqCC) of the lung and head and neck (SCCHN), including both efficacy and biomarker analyses...
January 17, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28174235/an-integrated-approach-identifies-mediators-of-local-recurrence-in-head-neck-squamous-carcinoma
#2
Francesca Citron, Joshua Armenia, Giovanni Franchin, Jerry Polesel, Renato Talamini, Sara D'Andrea, Sandro Sulfaro, Carlo M Croce, William Klement, Dave Otasek, Chiara Pastrello, Tomas Tokar, Igor Jurisica, Deborah French, Riccardo Bomben, Emanuela Vaccher, Diego Serraino, Barbara Belletti, Andrea Vecchione, Luigi Barzan, Gustavo Baldassarre
PURPOSE: Head and Neck Squamous Cell Carcinomas (HNSCC) cause more than 300,000 deaths worldwide each year. Locoregional and distant recurrences represent worse prognostic events and accepted surrogate markers of patients' survival. No valid biomarker and salvage therapy exist to identify and treat patients at high-risk of recurrence. We aimed to verify if selected microRNAs (miRs) could be used as biomarkers of recurrence in HNSCC. EXPERIMENTAL DESIGN: A Nanostring array was used to identify miRs associated with locoregional recurrence in 44 HNSCC patients...
February 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28127430/nos1-nos3-pik3ca-and-mapk-pathways-in-skin-following-radiation-therapy
#3
Steffen Koerdt, Nadine Tanner, Niklas Rommel, Nils H Rohleder, Gesche Frohwitter, Oliver Ristow, Klaus-Dietrich Wolff, Marco R Kesting
BACKGROUND: Essential molecular pathways such as the MAPK pathway, NO system, or the influence of PIK3CA as an oncogene are known to regulate fundamental signalling networks. However, few knowledge about their role in the occurrence of wound healing disorders (WHD) following radiation therapy (RT) exists. This study aims to evaluate the expression profiles of specific molecular pathway marker genes. METHODS: Expression profiles of the genes encoding MAPK, NOS1, NOS3, and PIK3CA were analyzed, by RT-PCR, in specimens from patients with and without a history of RT to the head and neck...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28123594/histone-deacetylase-inhibitor-saha-as-potential-targeted-therapy-agent-for-larynx-cancer-cells
#4
Aneta Grabarska, Jarogniew J Łuszczki, Ewa Nowosadzka, Ewelina Gumbarewicz, Witold Jeleniewicz, Magdalena Dmoszyńska-Graniczka, Krystyna Kowalczuk, Krzysztof Kupisz, Krzysztof Polberg, Andrzej Stepulak
Objective: Laryngeal squamous cell carcinoma is one of the most common malignant tumors in the head and neck region. Due to the poor response to chemotherapeutics in patients and low survival rate, successful treatment of larynx cancer still remains a challenge. Therefore, the identification of novel treatment options is needed. We investigated the anticancer effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, on two different laryngeal cancer cell lines RK33 and RK45. We also studied the antiproliferative action of SAHA in combination with cisplatin and defined the type of pharmacological interaction between these drugs...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28098869/core%C3%A2-shell-lipid-polymer-nanoparticles-for-combined-chemo%C3%A2-and-gene-therapy-of-childhood-head-and-neck-cancers
#5
Tiesong Zhang, Jing Ma, Chao Li, Ken Lin, Fan Lou, Hongchao Jiang, Yingqin Gao, Yanli Yang, Cheng Ming, Biao Ruan
Pediatric head and neck cancers account for overall 12% of all pediatric cancers. Despite recent advances in therapeutic modalities, children with tumor metastasis have poor prognosis. Therefore, there is an unmet need for new and effective treatment modalities for pediatric head and neck cancers. The present study describes a simple and efficient method for fabrication of cationic lipid‑polymer hybrid nanoparticles (CLPNs) for co‑delivery of cisplatin (CDDP) and DNA (CDDP/DNA CLPNs) for the therapy of childhood head and neck cancers...
January 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28072717/clinics-prognosis-and-new-therapeutic-options-in-patients-with-mucosal-melanoma-a-retrospective-analysis-of-75-patients
#6
Tim Schaefer, Imke Satzger, Ralf Gutzmer
Mucosal melanomas represent a rare entity with different risk factors and molecular features compared to cutaneous melanomas. They arise most commonly from mucosal surfaces in the head/neck region, the female genital tract (FGT) and the anorectal region. The aim of this study was to evaluate clinics, prognosis, and treatment options of patients with mucosal melanoma, in particular with regard to different primary sites.We retrospectively analyzed 75 patients with mucosal melanomas diagnosed in the years 1993 to 2015 in our department...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28055970/genomic-analysis-of-exceptional-responders-to-radiotherapy-reveals-somatic-mutations-in-atm
#7
Jennifer Ma, Jeremy Setton, Luc Morris, Pedro Blecua Carrillo Albornoz, Christopher Barker, Benjamin H Lok, Eric Sherman, Nora Katabi, Kathryn Beal, Ian Ganly, Simon N Powell, Nancy Lee, Timothy A Chan, Nadeem Riaz
Radiation therapy is a mainstay of cancer treatment, yet the molecular determinants of clinical response are poorly understood. We identified exceptional responders to radiotherapy based on clinical response, and investigated the associated tumor sequencing data in order to identify additional patients with similar mutations. Among head and neck squamous cell cancer patients receiving palliative radiotherapy at our institution, we identified one patient with documented complete metabolic response. Targeted sequencing analysis of the tumor identified a somatic frame-shift mutation in ATM, a gene known to be associated with radio-sensitivity in the germline...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28048945/organotypic-spheroid-culture-to-mimic-radiation-induced-salivary-hypofunction
#8
H S Shin, H Y An, J S Choi, H J Kim, J Y Lim
Radiation treatment often leads to irreversible damage to normal salivary glands (SGs) because of their proximity to head and neck cancers. Optimization of the in vitro model of irradiation (IR)-induced SG damage is warranted to investigate pathophysiology and monitor treatment outcome. Here, we present an organotypic spheroid culture model to investigate the impact of IR on SGs and the mechanisms underlying IR-induced structural and functional changes. Human parotid epithelial cells were obtained from human parotid glands and plated on either plastic plates or Matrigel...
December 1, 2016: Journal of Dental Research
https://www.readbyqxmd.com/read/28039063/encapsulation-of-primary-salivary-gland-cells-in-enzymatically-degradable-poly-ethylene-glycol-hydrogels-promotes-acinar-cell-characteristics
#9
Andrew D Shubin, Timothy J Felong, Brittany E Schutrum, Debria S L Joe, Catherine E Ovitt, Danielle S W Benoit
: Radiation therapy for head and neck cancers leads to permanent xerostomia due to the loss of secretory acinar cells in the salivary glands. Regenerative treatments utilizing primary submandibular gland (SMG) cells show modest improvements in salivary secretory function, but there is limited evidence of salivary gland regeneration. We have recently shown that poly(ethylene glycol) (PEG) hydrogels can support the survival and proliferation of SMG cells as multicellular spheres in vitro...
December 27, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/28024724/a-ppar-gamma-agonist-protects-against-oral-mucositis-induced-by-irradiation-in-a-murine-model
#10
Monica Mangoni, Mariangela Sottili, Chiara Gerini, Isacco Desideri, Cinzia Bastida, Stefania Pallotta, Francesca Castiglione, Pierluigi Bonomo, Icro Meattini, Daniela Greto, Emanuela Olmetto, Francesca Terziani, Carlotta Becherini, Camilla Delli Paoli, Laura Trombetta, Mauro Loi, Giampaolo Biti, Lorenzo Livi
BACKGROUND: Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR gamma agonist rosiglitazone is of interest in prevention and therapy of radiation-induced toxicities. We aimed to evaluate the radioprotective effect of rosiglitazone in a mouse model of radiation-induced oral mucositis. MATERIAL AND METHODS: Oral mucositis was obtained by irradiation of the oral region of C57BL/6J mice, pretreated or not with rosiglitazone. Mucositis was assessed by macroscopic scoring, histology and molecular analysis...
January 2017: Oral Oncology
https://www.readbyqxmd.com/read/28012797/ataxia-telangiectasia-mutated-interactor-regulates-head-and-neck-cancer-metastasis-via-kras-expression
#11
Yue-Ju Li, Wei-Ting Lai, Cheng-Chi Chang, Mark Yen-Ping Kuo, Yi-Ting Deng, Cheng-Ning Yang, Shih-Jung Cheng, Tai-Sheng Wu, Szu-Ta Chen, Been-Ren Lin
OBJECTIVES: Relapse is the most serious problem affecting the morbidity and mortality rates of patients with head and neck squamous cell carcinoma (HNSCC). Although HNSCC has been studied for several decades, the exact mechanism of cancer recurrence remains unclear. MATERIALS AND METHODS: ataxia-telangiectasia mutated interactor (ATMIN) messenger RNA(mRNA) expression was detected in HNSCC samples by quantitative RT-PCR, and was analyzed with patients' clinical outcomes by Kaplan-Meier analyses...
December 21, 2016: Oral Oncology
https://www.readbyqxmd.com/read/28004037/differential-compensation-mechanisms-define-resistance-to-pi3k-inhibitors-in-pik3ca-amplified-hnscc
#12
Nicole L Michmerhuizen, Elizabeth Leonard, Aditi Kulkarni, J Chad Brenner
OBJECTIVE: Recent sequencing studies of head and neck squamous cell carcinomas (HNSCCs) have identified the phosphatidylinositol 3-kinase (PI3K) pathway as the most frequently mutated, oncogenic pathway in this cancer type. Despite the frequency of activating genomic alterations in PIK3CA (the gene encoding the catalytic subunit of PI3K, targeted inhibitors of PI3K have not shown clinical efficacy as monotherapies. We hypothesized that co-dependent pathways, including the Ras-MEK-ERK pathway, may still be functional in the presence of PI3K inhibitors and might serve as mediators of this resistance...
2016: Otorhinolaryngol Head Neck Surg
https://www.readbyqxmd.com/read/27994592/kir-genes-and-their-ligands-predict-the-response-to-anti-egfr-monoclonal-antibodies-in-solid-tumors
#13
Cristina Morales-Estevez, Juan De la Haba-Rodriguez, Barbara Manzanares-Martin, Ignacio Porras-Quintela, Antonio Rodriguez-Ariza, Alberto Moreno-Vega, Maria J Ortiz-Morales, Maria A Gomez-España, Maria T Cano-Osuna, Javier Lopez-Gonzalez, Beatriz Chia-Delgado, Rafael Gonzalez-Fernandez, Enrique Aranda-Aguilar
Killer-cell immunoglobulin-like receptors (KIRs) regulate the killing function of natural killer cells, which play an important role in the antibody-dependent cell-mediated cytotoxicity response exerted by therapeutic monoclonal antibodies (mAbs). However, it is unknown whether the extensive genetic variability of KIR genes and/or their human leukocyte antigen (HLA) ligands might influence the response to these treatments. This study aimed to explore whether the variability in KIR/HLA genes may be associated with the variable response observed to mAbs based anti-epidermal growth factor receptor (EGFR) therapies...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27938998/epidermal-growth-factor-receptor-egfr-pathway-polymorphisms-as-predictive-markers-of-cetuximab-toxicity-in-locally-advanced-head-and-neck-squamous-cell-carcinoma-hnscc-in-a-spanish-population
#14
J Fernández-Mateos, R Seijas-Tamayo, R Mesía, M Taberna, M Pastor Borgoñón, E Pérez-Ruiz, J C Adansa Klain, S Vázquez Fernández, E Del Barco Morillo, A Lozano, R González Sarmiento, J J Cruz-Hernández
OBJECTIVES: To examine the relationship between polymorphisms of the epidermal growth factor receptor (EGFR) pathway and toxicity in head and neck squamous cell carcinoma (HNSCC) patients treated with cetuximab. MATERIAL AND METHODS: Multicenter, retrospective, observational pilot study which included 110 patients with histologically-confirmed human papillomavirus (HPV) negative HNSCC in locally advanced stages (III-IVA-B) and who were treated with chemotherapy and radiotherapy plus cetuximab between 2003 and 2013...
December 2016: Oral Oncology
https://www.readbyqxmd.com/read/27924064/toward-the-use-of-precision-medicine-for-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#15
Wang Gong, Yandi Xiao, Zihao Wei, Yao Yuan, Min Qiu, Chongkui Sun, Xin Zeng, Xinhua Liang, Mingye Feng, Qianming Chen
Precision medicine is a new strategy that aims at preventing and treating human diseases by focusing on individual variations in people's genes, environment and lifestyle. Precision medicine has been used for cancer diagnosis and treatment and shows evident clinical efficacy. Rapid developments in molecular biology, genetics and sequencing technologies, as well as computational technology, has enabled the establishment of "big data", such as the Human Genome Project, which provides a basis for precision medicine...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27914687/braf-nras-kit-tert-gnaq-gna11-mutation-profile-analysis-of-head-and-neck-mucosal-melanomas-a-study-of-42-cases
#16
Şule Öztürk Sari, İsmaİl Yilmaz, Orhun Çiğ Taşkin, Gİzem Narli, Fatma Şen, Şenol Çomoğlu, Pinar Firat, Bİlge Bİlgİç, Dİlek Yilmazbayhan, Yasemİn Özlük, Nesİmİ Büyükbabanİ
Head and neck mucosal melanoma (HNMuM), which occurs mostly in the sinonasal and oral cavity, constitutes less than 1% of all malignant melanomas. Treatment options fail to improve the prognosis of this aggressive tumour that has low overall survival rates. Thus, development of new targeted therapies is essential. Unfortunately, limited data exist regarding their molecular profile. BRAF, NRAS, KIT, TERT and GNAQ/GNA11 oncogene mutations were investigated in 42 HNMuMs (28 sinonasal, 13 oral, 1 nasopharyngeal)...
January 2017: Pathology
https://www.readbyqxmd.com/read/27901488/cancer-associated-fibroblasts-promote-cancer-cell-growth-through-a-mir-7-rassf2-par-4-axis-in-the-tumor-microenvironment
#17
Zongze Shen, Xing Qin, Ming Yan, Rongrong Li, Gang Chen, Jianjun Zhang, Wantao Chen
Cancer-associated fibroblasts (CAFs), a major component of cancer stroma, play an important role in cancer progression but little is known about how CAFs affect tumorigenesis and development. MicroRNAs (miRNAs) are small non-coding RNAs that can negatively regulate target mRNA expression at post-transcriptional levels. In head and neck cancer (HNC), our analysis of miRNA arrays showed that miR-7, miR-196 and miR-335 were significantly up-regulated in CAFs when compared with their paired normal fibroblasts (NFs)...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27895714/early-detection-and-personalized-treatment-in-oral-cancer-the-impact-of-omics-approaches
#18
REVIEW
Ilda Patrícia Ribeiro, Leonor Barroso, Francisco Marques, Joana Barbosa Melo, Isabel Marques Carreira
BACKGROUND: Oral cancer is one of the most common malignant lesions of the head and neck. This cancer is an aggressive and lethal disease with no significant improvements in the overall survival in the last decades. Moreover, the incidence of oral HPV-positive tumors is rising, especially in young people. This oral neoplasm develops through numerous molecular imbalances that affect key genes and signaling pathways; however, the molecular mechanisms involved in the pathogenesis and progression of oral tumors are still to be fully determined...
2016: Molecular Cytogenetics
https://www.readbyqxmd.com/read/27867017/genomic-amplification-of-fanconi-anemia-complementation-group-a-fanca-in-head-and-neck-squamous-cell-carcinoma-hnscc-cellular-mechanisms-of-radioresistance-and-clinical-relevance
#19
Julia Hess, Kristian Unger, Michael Orth, Ulrike Schötz, Lars Schüttrumpf, Verena Zangen, Igor Gimenez-Aznar, Agata Michna, Ludmila Schneider, Ramona Stamp, Martin Selmansberger, Herbert Braselmann, Ludwig Hieber, Guido A Drexler, Sebastian Kuger, Diana Klein, Verena Jendrossek, Anna A Friedl, Claus Belka, Horst Zitzelsberger, Kirsten Lauber
Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27863405/identification-of-evolutionarily-conserved-dna-damage-response-genes-that-alter-sensitivity-to-cisplatin
#20
Anna V Gaponova, Alexander Y Deneka, Tim N Beck, Hanqing Liu, Gregory Andrianov, Anna S Nikonova, Emmanuelle Nicolas, Margret B Einarson, Erica A Golemis, Ilya G Serebriiskii
Ovarian, head and neck, and other cancers are commonly treated with cisplatin and other DNA damaging cytotoxic agents. Altered DNA damage response (DDR) contributes to resistance of these tumors to chemotherapies, some targeted therapies, and radiation. DDR involves multiple protein complexes and signaling pathways, some of which are evolutionarily ancient and involve protein orthologs conserved from yeast to humans. To identify new regulators of cisplatin-resistance in human tumors, we integrated high throughput and curated datasets describing yeast genes that regulate sensitivity to cisplatin and/or ionizing radiation...
November 15, 2016: Oncotarget
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