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Gene Therapy AND Head and Neck

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https://www.readbyqxmd.com/read/28335614/therapeutic-targeting-of-protein-kinase-ck2-gene-expression-in-feline-oral-squamous-cell-carcinoma-a-naturally-occurring-large-animal-model-of-head-and-neck-cancer
#1
Claire Cannon, Janeen Trembley, Betsy Kren, Gretchen Unger, M Gerard O'Sullivan, Ingrid Cornax, Jaime Modiano, Khalil Ahmed
Protein kinase CK2 (CK2) is a highly promising target for cancer therapy and anti-CK2 gene expression therapy has shown effectiveness in rodent models of human head and neck cancer (HNC). To date, there has been no large animal model of cancer in which to further explore anti-CK2 therapies. Feline oral squamous cell carcinoma (FOSCC) has been proposed as a large animal model for human HNC and we have previously shown that CK2 is a rational target in FOSCC. We hypothesized that a novel tenfibgen coated tumor-specific nanocapsule carrying RNAi oligonucleotides targeting feline CK2α and CK2α' (TBG-RNAi-fCK2αα') would be safe in cats with FOSCC...
March 23, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28315228/clinical-value-of-monoclonal-antibodies-and-tyrosine-kinase-inhibitors-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#2
REVIEW
Wiktoria Blaszczak, Wojciech Barczak, Anna Wegner, Wojciech Golusinski, Wiktoria Maria Suchorska
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of malignant tumours that affects over 500,000 patients per year. Treatment failure is generally due to the heterogeneity of these tumours and to the serious adverse effects associated with treatment. Immunological system impairment, which is common in HNSCC, further contributes to treatment failure by mediating tumour escape mechanisms. To date, the only clinically approved targeted therapy agent is cetuximab, a monoclonal antibody (mAb) that binds to, and inhibits, epidermal growth factor receptor, which is widely overexpressed in HNSCC...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28295222/traf3-cyld-mutations-identify-a-distinct-subset-of-human-papilloma-virus-associated-head-and-neck-squamous-cell-carcinoma
#3
Michael Hajek, Andrew Sewell, Susan Kaech, Barbara Burtness, Wendell G Yarbrough, Natalia Issaeva
BACKGROUND: The incidence of human papillomavirus (HPV)-associated (HPV-positive) head and neck squamous cell carcinoma (HNSCC) of the oropharynx has dramatically increased over the last decade and continues to rise. Newly diagnosed HPV-positive HNSCCs in the United States currently outnumber any other HPV-associated cancers, including cervical cancer. Despite introduction of the HPV vaccine, the epidemic of HPV-positive HNSCC is expected to continue for approximately 60 years. Compared with patients who have tobacco-associated HNSCC, those who have HPV-positive HNSCC have better overall survival and response to treatment...
March 13, 2017: Cancer
https://www.readbyqxmd.com/read/28277541/the-foxm1-abcc5-axis-contributes-to-paclitaxel-resistance-in-nasopharyngeal-carcinoma-cells
#4
Youxiang Hou, Qianling Zhu, Zheng Li, Yongbo Peng, Xiaohui Yu, Bowen Yuan, Yijun Liu, Youhong Liu, Linglong Yin, Yuchong Peng, Zhenghua Jiang, Jinping Li, Bowen Xie, Yumei Duan, Guolin Tan, Kurban Gulina, Zhicheng Gong, Lunquan Sun, Xuegong Fan, Xiong Li
Paclitaxel is clinically used as a first-line chemotherapeutic regimen for several cancer types, including head and neck cancers. However, acquired drug resistance results in the failure of therapy, metastasis and relapse. The drug efflux mediated by ATP-binding cassette (ABC) transporters and the survival signals activated by forkhead box (FOX) molecules are critical in the development of paclitaxel drug resistance. Whether FOX molecules promote paclitaxel resistance through drug efflux remains unknown. In this study, we developed several types of paclitaxel-resistant (TR) nasopharyngeal carcinoma (NPC) cells...
March 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28258440/comprehensive-characterization-of-genes-associated-with-the-tp53-signal-transduction-pathway-in-various-tumors
#5
Shumpei Ohnami, Keiichi Ohshima, Takeshi Nagashima, Kenichi Urakami, Yuji Shimoda, Junko Saito, Akane Naruoka, Keiichi Hatakeyama, Tohru Mochizuki, Masakuni Serizawa, Sumiko Ohnami, Masatoshi Kusuhara, Ken Yamaguchi
The TP53 signal transduction pathway is an attractive target for cancer treatments. In this study, we conducted a comprehensive molecular evaluation of 907 patients with cancer in Japan to identify genomic alterations in the TP53 pathway. TP53 mutations were frequently detected in many cancers, except melanoma, thymic tumors, gastrointestinal stromal tumors, and renal cancers. The frequencies of non-synonymous single nucleotide variants (SNVs) in the TP53 family members TP63 and TP73 were relatively low, although genes with increased frequencies of SNVs were as follows: PTEN (11...
March 3, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28254861/recommended-guidelines-for-validation-quality-control-and-reporting-of-tp53-variants-in-clinical-practice
#6
REVIEW
Bernard Leroy, Mandy L Ballinger, Fanny Baran-Marszak, Gareth L Bond, Antony Braithwaite, Nicole Concin, Lawrence A Donehower, Wafik S El-Deiry, Pierre Fenaux, Gianluca Gaidano, Anita Langerød, Eva Hellstrom-Lindberg, Richard Iggo, Jacqueline Lehmann-Che, Phuong L Mai, David Malkin, Ute M Moll, Jeffrey N Myers, Kim E Nichols, Sarka Pospisilova, Patricia Ashton-Prolla, Davide Rossi, Sharon A Savage, Louise C Strong, Patricia N Tonin, Robert Zeillinger, Thorsten Zenz, Joseph F Fraumeni, Peter E M Taschner, Pierre Hainaut, Thierry Soussi
Accurate assessment of TP53 gene status in sporadic tumors and in the germline of individuals at high risk of cancer due to Li-Fraumeni Syndrome (LFS) has important clinical implications for diagnosis, surveillance, and therapy. Genomic data from more than 20,000 cancer genomes provide a wealth of information on cancer gene alterations and have confirmed TP53 as the most commonly mutated gene in human cancer. Analysis of a database of 70,000 TP53 variants reveals that the two newly discovered exons of the gene, exons 9β and 9γ, generated by alternative splicing, are the targets of inactivating mutation events in breast, liver, and head and neck tumors...
March 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28249647/a-clinicopathologic-study-on-ss18-fusion-positive-head-and-neck-synovial-sarcomas
#7
Adepitan A Owosho, Cherry L Estilo, Evan B Rosen, SaeHee K Yom, Joseph M Huryn, Cristina R Antonescu
OBJECTIVE: To determine clinicopathologic factors on survival in patients with head and neck synovial sarcoma. PATIENTS AND METHODS: We retrospectively identified patients with molecularly confirmed synovial sarcomas of the head and neck (SS-HN), either by the presence of SS18-SSX fusion transcript by RT-PCR or SS18 gene rearrangement by FISH, who were managed at our institution over a 20-year period (1996-2015). Kaplan-Meier survival analysis and log-rank test were performed to evaluate variables related to disease specific survival (DSS)...
March 2017: Oral Oncology
https://www.readbyqxmd.com/read/28236344/integration-of-high-risk-human-papillomavirus-into-cellular-cancer-related-genes-in-head-and-neck-cancer-cell-lines
#8
Heather M Walline, Christine M Goudsmit, Jonathan B McHugh, Alice L Tang, John H Owen, Bin T Teh, Erin McKean, Thomas W Glover, Martin P Graham, Mark E Prince, Douglas B Chepeha, Steven B Chinn, Robert L Ferris, Susanne M Gollin, Thomas K Hoffmann, Henning Bier, Ruud Brakenhoff, Carol R Bradford, Thomas E Carey
BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16- and HPV18-positive squamous cell carcinoma lines. METHODS: E6/E7 alternate transcripts were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Detection of integrated papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites and affected host genes...
February 25, 2017: Head & Neck
https://www.readbyqxmd.com/read/28225558/cutaneous-adnexal-adenocarcinoma-with-exquisite-sensitivity-to-trastuzumab
#9
Timothy J Brown, David J Sher, Lucien A Nedzi, Randall S Hughes, Muhammad S Beg, Jason Mull, Venetia R Sarode, Saad A Khan
BACKGROUND: Cutaneous adnexal adenocarcinoma is a rare cancer that is occasionally human epidermal growth factor receptor-2 (HER-2)-positive, and demonstrates variable response to HER-2 inhibitors. METHODS: We report a case of adnexal adenocarcinoma of the scalp in a 56-year-old man. He underwent wide local excision with cervical node dissection followed by radiation, but had extensive local recurrence. RESULTS: Pathology demonstrated a poorly differentiated adnexal adenocarcinoma with HER-2 overexpression by immunohistochemistry (IHC) and high HER-2 gene amplification by fluorescence in situ hybridization...
February 22, 2017: Head & Neck
https://www.readbyqxmd.com/read/28216066/the-potential-effect-of-oral-microbiota-in-the-prediction-of-mucositis-during-radiotherapy-for-nasopharyngeal-carcinoma
#10
Xiao-Xia Zhu, Xiao-Jun Yang, Yi-Lan Chao, Hui-Min Zheng, Hua-Fang Sheng, Hai-Yue Liu, Yan He, Hong-Wei Zhou
BACKGROUND: Oral mucositis is probably the most debilitating complication that can arise in treating a patient with head and neck cancer. Little is known about the impacts of oral microbiota on the initiation and progression of mucositis. METHODS: Based on 16S rRNA gene sequencing, dynamic changes in oral bacterial profile as well as correlations between the severity of mucositis and bacterial shifts during radiotherapy were investigated. FINDINGS: Our results revealed that bacterial community structure altered progressively during radiation therapy, in parallel with a marked increase in the relative abundance of some Gram-negative bacteria...
February 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28192747/biology-and-patterns-of-response-to-egfr-inhibition-in-squamous-cell-cancers-of-the-lung-and-head-neck
#11
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...
March 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28174235/an-integrated-approach-identifies-mediators-of-local-recurrence-in-head-neck-squamous-carcinoma
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
April 2017: 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
#19
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. To further develop this approach for cell-based salivary gland regeneration, we have investigated how different modes of PEG hydrogel degradation affect the proliferation, cell-specific gene expression, and epithelial morphology within encapsulated salivary gland spheres...
March 1, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28024724/a-ppar-gamma-agonist-protects-against-oral-mucositis-induced-by-irradiation-in-a-murine-model
#20
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
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