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https://www.readbyqxmd.com/read/28923211/nivolumab-and-pembrolizumab-monoclonal-antibodies-against-programmed-cell-death-1-pd-1-that-are-interchangeable
#1
REVIEW
Vinay Prasad, Victoria Kaestner
Nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY) and pembrolizumab (Keytruda, Merck, Kenilworth, NJ) are the first two US Food and Drug Administration (FDA)-approved monoclonal antibodies targeting programmed death-1 (PD-1). Nivolumab and pembrolizumab work by interfering with the interaction between PD-1 and programmed death ligand-1 (PD-L1), whose unimpeded interaction downregulates T cells allowing cancer cells to evade immune surveillance. These drugs have earned a series of FDA approvals for melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial cancer, classical Hodgkin lymphoma, and renal cell cancer...
April 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28920960/long-noncoding-rna-egfr-as1-mediates-epidermal-growth-factor-receptor-addiction-and-modulates-treatment-response-in-squamous-cell-carcinoma
#2
Daniel S W Tan, Fui Teen Chong, Hui Sun Leong, Shen Yon Toh, Dawn P Lau, Xue Lin Kwang, Xiaoqian Zhang, Gopinath M Sundaram, Gek San Tan, Mei Mei Chang, Boon Tin Chua, Wan Teck Lim, Eng Huat Tan, Mei Kim Ang, Tony K H Lim, Prabha Sampath, Balram Chowbay, Anders J Skanderup, Ramanuj DasGupta, N Gopalakrishna Iyer
Targeting EGFR is a validated approach in the treatment of squamous-cell cancers (SCCs), although there are no established biomarkers for predicting response. We have identified a synonymous mutation in EGFR, c.2361G>A (encoding p.Gln787Gln), in two patients with head and neck SCC (HNSCC) who were exceptional responders to gefitinib, and we showed in patient-derived cultures that the A/A genotype was associated with greater sensitivity to tyrosine kinase inhibitors (TKIs) as compared to the G/A and G/G genotypes...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28919706/profile-of-pembrolizumab-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma-design-development-and-place-in-therapy
#3
REVIEW
Sulsal Haque, Mahender Yellu, Jaskirat Randhawa, Nooshin Hashemi-Sadraei
Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy worldwide, and despite advances in cytotoxic, surgical and radiation techniques, outcomes are still poor in those with both locally advanced and metastatic diseases. The need for development of better therapeutics along with a greater understanding of the relationship between the immune system and malignancies has led to a new therapeutic modality, immune modulators, particularly checkpoint inhibitors in HNSCC. It is now well recognized that HNSCC circumvents crucial pathways utilized by the immune system to escape surveillance...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28919248/safety-of-differential-radiation-dosing-in-lymph-node-positive-necks-treated-with-imrt
#4
Stephen Sozio, Zorimar Rivera-Núñez, Omar Mahmoud, Sung Kim
PURPOSE: When treating head and neck squamous cell carcinoma (HNSCC) with intensity modulated radiation therapy (IMRT), it is common to use several dose levels for a lymph node positive neck: full dose (66-70 Gy) to gross cancer, intermediate dose (59-63 Gy) to higher risk neck regions, and standard dose (50-54 Gy) to lower risk neck regions. There is no consensus regarding how much of the neck should receive intermediate versus standard dose, however. METHODS AND MATERIALS: HNSCC patients treated with IMRT were identified from 2 academic medical centers between 2004 and 2016...
July 19, 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28918429/synergy-of-dendritic-cell-vaccines-and-avasimibe-in-treatment-of-head-and-neck-cancer-in-mice
#5
Xin Chen, Qibin Song, Leiming Xia, Ximing Xu
BACKGROUND The main purpose of this study was to explore the antitumor effect and mechanisms of ACAT1 inhibitor combined with CSCs-DC vaccine. MATERIAL AND METHODS We isolated HNSCC CSCs and gained CSCs antigens, then used CSCs antigens to load dendritic cells (DC) and generated a CSCs-DC vaccine. We treated mice after surgical excision of established SCC7 tumors with CSCs-DC vaccine and/or ACAT1 inhibitor, and recorded local tumor relapse and host survival. T cells and B cells were harvested from mice treated with CSCs-DC vaccine and/or ACAT1 inhibitor...
September 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28916527/demethylation-therapy-as-a-targeted-treatment-for-human-papilloma-virus-associated-head-and-neck-cancer
#6
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/28916224/lack-of-differences-in-radiation-induced-immunogenicity-parameters-between-hpv-positive-and-hpv-negative-human-hnscc-cell-lines
#7
Karolin Schneider, Vanesa Bol, Vincent Grégoire
BACKGROUND AND PURPOSE: Clinical studies indicate that patients with HPV/p16-associated head & neck squamous cell carcinoma (HNSCC) represent a subgroup with a better prognosis and improved response to conventional radiotherapy. Involvement of immune-based factors has been hypothesized. In the present study, we investigated radiation-induced differences in release of damage associated molecular patterns (DAMPs), cytokines and activation of dendritic cells (DCs) in HPV-positive and negative HNSCC cancer cell lines...
September 12, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28915663/mir-223-3p-inhibits-angiogenesis-and-promotes-resistance-to-cetuximab-in-head-and-neck-squamous-cell-carcinoma
#8
Alexandre Bozec, Joséphine Zangari, Mathilde Butori-Pepino, Marius Ilie, Salomé Lalvee, Thierry Juhel, Catherine Butori, Patrick Brest, Paul Hofman, Valérie Vouret-Craviari
MicroRNAs (miRs) participate in tumor growth and dissemination by regulating expression of various target genes. MiR-223-3p is suspected of being involved in head and neck squamous cell carcinoma (HNSCC) growth although its precise role has not been elucidated. In this study, we showed that miR-223-3p is present in biopsies of HNSCC patients and that its presence is correlated with high neutrophil infiltrate. We found that overexpression of miR-223-3p slightly increased proliferation of the CAL27 squamous carcinoma cell line both in vitro and in vivo...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915597/il-8-promotes-inflammatory-mediators-and-stimulates-activation-of-p38-mapk-erk-nf-%C3%AE%C2%BAb-pathway-and-reduction-of-jnk-in-hnscc
#9
Leong-Perng Chan, Cheng Liu, Feng-Yu Chiang, Ling-Feng Wang, Ka-Wo Lee, Wan-Ting Chen, Po-Lin Kuo, Chia-Hua Liang
This investigation identifies interleukin 8 (IL-8) as the main inflammatory mediator in head and neck squamous cell carcinoma (HNSCC). The expressions of chemokines of IL-8, IL-1β and IL-6 and the cytokines of tumor necrosis factor-α (TNF-α) were higher in HNSCC patient tissues than in non-cancerous matched tissues (NCMT) whereas the expression of IL-10 was lower. IL-8 is most highly expressed in the tissues of patients with HNSCC. Treatment of HNSCC cells with IL-8 increased the secretion of IL-1β, IL-6 and TNF-α and reduced IL-10 expression; the increase in the expression of IL-1β was particularly considerable...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915554/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#10
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913156/head-and-neck-pet-ct-therapy-response-interpretation-criteria-hopkins-criteria-external-validation-study
#11
Ayse Tuba Kendi, David Brandon, Jeffrey Switchenko, Jeffery Trad Wadsworth, Mark W El-Deiry, Nabil F Saba, David M Schuster, Rathan M Subramaniam
Qualitative assessment of PET/CT results in post therapy is very important to provide a reproducible and systemic reporting. A recently introduced response criteria, known as the Hopkins criteria showed promising results. Our aim is to externally validate the Hopkins interpretation system to assess therapy response in head and neck squamous cell cancer (HNSCC). The study included 69 biopsy proven HNSCC patients who underwent post therapy PET/CT between 5-24 weeks after completion of therapy. PET/CT images were interpreted by one nuclear medicine physician and one nuclear radiologist, independently...
2017: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28910149/dual-targeting-of-epidermal-growth-factor-receptor-and-her3-by-mehd7945a-as-monotherapy-or-in-combination-with-cisplatin-partially-overcomes-cetuximab-resistance-in-head-and-neck-squamous-cell-carcinoma-cell-lines
#12
Ines De Pauw, An Wouters, Jolien Van den Bossche, Vanessa Deschoolmeester, Hasan Baysal, Patrick Pauwels, Marc Peeters, Jan B Vermorken, Filip Lardon
Aberrant signaling of the epidermal growth factor receptor (EGFR) plays a crucial role in the tumorigenesis of many cancer types, including head and neck squamous cell carcinoma (HNSCC), making it a compelling drug target. After initial promising results of EGFR-targeted therapies such as cetuximab, the problem of therapeutic resistance is emerging and new treatment options are necessary. In contrast to first-generation EGFR inhibitors, MEHD7945A (duligotuzumab) is a monoclonal antibody with dual EGFR/HER3 specificity...
September 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28905170/-follow-up-ultrasound-of-head-and-neck-cancer
#13
J Künzel, A Bozzato, S Strieth
In Germany high-resolution sonography using the color duplex mode in addition to computed tomography (CT) is a well-established and proven method in the context of restaging after primary therapy of head and neck squamous cell cancer (HNSCC). There are no international evidence-based restaging guidelines. Decisions concerning neck dissection (ND) after primary radiochemotherapy (RCT) are often individually derived in the respective tumor conferences and are therefore subject to variance. Compared to the UK or USA, in Germany there is a high level of expertise in the use of ultrasound in combination with CT for the routine restaging of HNSCC after RCT...
September 13, 2017: HNO
https://www.readbyqxmd.com/read/28903447/locoregionally-recurrent-head-and-neck-squamous-cell-carcinoma-incidence-survival-prognostic-factors-and-treatment-outcomes
#14
Jer-Hwa Chang, Chia-Che Wu, Kevin Sheng-Po Yuan, Alexander T H Wu, Szu-Yuan Wu
PURPOSE: For locoregionally recurrent head and neck squamous cell carcinoma (HNSCC), appropriate therapeutic decisions remain unclear. We examined the treatment outcomes of a national cohort to determine suitable treatments for and prognostic factors in patients with locoregionally recurrent HNSCCs at different stages and sites. PATIENTS AND METHODS: We analyzed data of >20-year-old patients with HNSCC at American Joint Committee on Cancer clinical stages I-IV without metastasis from Taiwan National Health Insurance and cancer registry databases...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903437/meta-analysis-of-micrornas-expression-in-head-and-neck-cancer-uncovering-association-with-outcome-and-mechanisms
#15
Joshua Lubov, Mariana Maschietto, Iman Ibrahim, Alex Mlynarek, Michael Hier, Luiz Paulo Kowalski, Moulay A Alaoui-Jamali, Sabrina Daniela da Silva
Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at advanced stages, incurring significant high mortality and morbidity. This review explored the risk stratification of miRNAs, and investigated the impact of miRNA networking in HNSCC prognostication. We performed a meta-analysis and a systematic literature search on online databases for papers published prior to December 1, 2016. The list of miRNAs was uploaded to MetacoreTM to construct a protein-protein interaction network, which was used to identify targets of the miRNAs and potential drugs...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903353/direct-inhibition-of-stat-signaling-by-platinum-drugs-contributes-to-their-anti-cancer-activity
#16
Stanleyson V Hato, Carl G Figdor, Susumu Takahashi, Anja E Pen, Altuna Halilovic, Kalijn F Bol, Angela Vasaturo, Yukie Inoue, Nienke de Haas, Dagmar Verweij, Carla M L Van Herpen, Johannes H Kaanders, Johan H J M van Krieken, Hanneke W M Van Laarhoven, Gerrit K J Hooijer, Cornelis J A Punt, Akira Asai, I Jolanda M de Vries, W Joost Lesterhuis
Platinum-based chemotherapeutics are amongst the most powerful anti-cancer drugs. Although their exact mechanism of action is not well understood, it is thought to be mediated through covalent DNA binding. We investigated the effect of platinum-based chemotherapeutics on signaling through signal transducer and activator of transcription (STAT) proteins, which are involved in many oncogenic signaling pathways. We performed in vitro experiments in various cancer cell lines, investigating the effects of platinum chemotherapeutics on STAT phosphorylation and nuclear translocation, the expression of STAT-modulating proteins and downstream signaling pathways...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902347/measuring-the-response-of-human-head-and-neck-squamous-cell-carcinoma-to-irradiation-in-a-microfluidic-model-allowing-customized-therapy
#17
Ramsah Cheah, Rishi Srivastava, Nicholas D Stafford, Andrew W Beavis, Victoria Green, John Greenman
Radiotherapy is the standard treatment for head and neck squamous cell carcinoma (HNSCC), however, radioresistance remains a major clinical problem despite significant improvements in treatment protocols. Therapeutic outcome could potentially be improved if a patient's tumour response to irradiation could be predicted ex vivo before clinical application. The present study employed a bespoke microfluidic device to maintain HNSCC tissue whilst subjecting it to external beam irradiation and measured the responses using a panel of cell death and proliferation markers...
October 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28901527/hypoxia-promotes-migration-invasion-and-glycolysis-in-head-and-neck-squamous-cell-carcinoma-via-an-hif-1%C3%AE-mtdh-loop
#18
Gangcai Zhu, Fusen Peng, Wei Gong, Li She, Ming Wei, Haolei Tan, Changhan Chen, Diekuo Zhang, Guo Li, Donghai Huang, Xin Zhang, Yong Liu
Hypoxia is a hallmark of progressive cancer. Hypoxic cancer cells trigger glycolysis in response to a decreased O2 supply to meet metabolic and bioenergetic demands. Meanwhile, these responses to hypoxia and alterations of the microenvironment promote cancer cell metastasis by increasing transcription of hypoxia-inducible factor (HIF)-regulated genes. However, the detailed mechanism by which hypoxia regulates cancer cell metastasis and glycolysis remains to be investigated. In the present study, we identified that metadherin (MTDH), a multifaceted oncogene, is involved in the regulation of head and neck squamous cell carcinoma (HNSCC) metastasis and invasion under hypoxic conditions...
September 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28900608/comparative-analysis-of-microrna-expression-among-benign-and-malignant-tongue-tissue-and-plasma-of-patients-with-tongue-cancer
#19
Guilherme Rabinowits, Michaela Bowden, Ludmila M Flores, Sigitas Verselis, Victoria Vergara, Vickie Y Jo, Nicole Chau, Jochen Lorch, Peter S Hammerman, Tom Thomas, Laura A Goguen, Donald Annino, Jonathan D Schoenfeld, Danielle N Margalit, Roy B Tishler, Robert I Haddad
BACKGROUND: Identification of a microRNA (miRNA) pattern to be used as a biomarker for HNSCC is challenging given the heterogeneity of the disease and different methodologies used. To better define the field, we performed a prospective analysis of blood, tumor, and paired benign tissues in tongue squamous cell carcinoma (SCC) patients. METHODS: Plasma samples were collected prior to surgery, and paired tumor and benign tissue blocks were collected from tongue cancer resections...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28899969/tmem16a-ano1-inhibits-apoptosis-via-down-regulation-of-bim-expression
#20
Neal R Godse, Nayel I Khan, Zachary A Yochum, Roberto Gomez-Casal, Carolyn Kemp, Daniel J Shiwarski, Raja Seethala, Scott Kulich, Mukund Seshadri, Timothy F Burns, Umamaheswar Duvvuri
PURPOSE: TMEM16A is a calcium-activated chloride channel that is amplified in a variety of cancers, including 30% of head and neck squamous cell carcinomas (HNSCC), raising the possibility of an anti-apoptotic role in malignant cells. The present study investigated this using a multi-modal, translational investigation. EXPERIMENTAL DESIGN: Combination of 1) in vitro HNSCC cell culture experiments assessing cell viability, apoptotic activation, and protein expression 2) in vivo studies assessing similar outcomes, and 3) molecular and staining analysis of human HNSCC samples...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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