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Article: Dual PI3K/mTOR inhibitors: does p53 modulate response?

Ekshyyan, Oleksandr / Anandharaj, Arunkumar / Nathan, Cherie-Ann O

Clinical cancer research : an official journal of the American Association for Cancer Research

2013 Volume 19, Issue 14, Page(s) 3719–3721

Abstract: Head and neck squamous cell carcinomas have multiple genetic alterations that can influence clinical response to treatment. It is important to evaluate how distinct alterations affect response to targeted agents to identify a subset of patients who can ... ...

Abstract	Head and neck squamous cell carcinomas have multiple genetic alterations that can influence clinical response to treatment. It is important to evaluate how distinct alterations affect response to targeted agents to identify a subset of patients who can benefit from therapy, improving survival and decreasing toxicity.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Carcinoma, Squamous Cell/therapy ; Female ; Head and Neck Neoplasms/therapy ; Humans ; Pyridones/pharmacology ; Pyrimidines/pharmacology ; Tumor Suppressor Protein p53/genetics
Chemical Substances	2-amino-8-(4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido(2,3-d)pyrimidin-7(8H)-one ; Antineoplastic Agents ; Pyridones ; Pyrimidines ; TP53 protein, human ; Tumor Suppressor Protein p53
Language	English
Publishing date	2013-07-15
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-13-1291
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Zs.A 4223: Show issues

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Article: Local and systemic Curcumin C3 complex inhibits 4NQO-induced oral tumorigenesis

Khandelwal, Alok R / Moore-Medlin, Tara / Ekshyyan, Oleksandr / Gu, Xin / Abreo, Fleurette / Nathan, Cherie-Ann O

American journal of cancer research

2018 Volume 8, Issue 12, Page(s) 2538–2547

Abstract: Head and Neck Squamous cell carcinoma (HNSCC) can be characterized by synchronous tumors in the upper aerodigestive tract. Second primary tumors as a result of field cancerization are a significant problem amongst patients with risk factors for HNSCC, ... ...

Abstract	Head and Neck Squamous cell carcinoma (HNSCC) can be characterized by synchronous tumors in the upper aerodigestive tract. Second primary tumors as a result of field cancerization are a significant problem amongst patients with risk factors for HNSCC, indicating a need for chemo preventive agents. We investigated the efficacy of local and systemic Curcumin C3 complex (C3); a purified mixture of Curcumin, bisdemethoxy Curcumin and demethoxy Curcumin as a chemo preventative agent in 4-nitroquinoline-1-oxide (4NQO)-induced tumorigenesis in mice. The effect of local C3 application was compared to C3 administered orally and in combination with systemic administration. C57Bl/6 mice were administered 4NQO (50 µg/ml) in the drinking water for 16 weeks. At 12 weeks, mice were subjected to daily treatment with either vehicle (control), or 15 mg C3 complex by local delivery, gavage, or combined local and gavage for 28 days (16 week time point), and followed up to 22 weeks. Compared to local and oral systemic C3 administration, combination of local and systemic application significantly decreased multiplicity of 4NQO-induced preneoplastic and neoplastic lesions (p<0.05). Treatment with C3 correlated with a decrease in cell proliferation compared to the 4NQO group. Further, pre-treatment with C3 complex significantly attenuated 4NQO induced expression of basic fibroblast growth factor (FGF-2) and its cognate receptor FGFR-2, suggesting an important role of FGF-2/FGFR-2 axis in chemoprevention of HNSCC (p<0.05). Our findings suggest that a combination of local and systemic C3 complex could effectively target proliferation and inhibit 4NQO-induced tumorigenesis
Language	English
Publishing date	2018-12-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2589522-9
ISSN	2156-6976
ISSN	2156-6976
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Article ; Online: Survival outcomes based on systemic agent used concurrently with radiation in human-papillomavirus associated oropharyngeal cancer.

Mehta, Vikas / Moore-Medlin, Tara / Flores, Jose M / Ma, Xiaohui / Ekshyyan, Oleksandr / Nathan, Cherie-Ann O

Oncotarget

2017 Volume 8, Issue 41, Page(s) 70907–70915

Abstract: Purpose: To investigate survival outcomes of patients treated with concurrent cetuximab and radiotherapy for primary management of both HPV positive and negative OPSCC, and compare the results to traditional platinum-based therapy. We hypothesize that ... ...

Abstract	Purpose: To investigate survival outcomes of patients treated with concurrent cetuximab and radiotherapy for primary management of both HPV positive and negative OPSCC, and compare the results to traditional platinum-based therapy. We hypothesize that the use of cetuximab in the HPV positive OPSCC patients will result in inferior survival based on tumor biological differences. Study design: A single institution retrospective analysis of 304 patients. The primary outcomes of interest were 1) overall survival and 2) relapse free survival. Pearson Chi-square tests were used to compare proportions between subgroups. One-way analysis of variance was used to compare the continuous variable age between subgroups. Kaplan-Meier method was used to produce survival curves, and comparisons between survival curves were made using the log-rank test. The survival functions comparing subgroups of chemotherapy were analyzed using semi-parametric (i.e. Cox proportional hazards models) and fully parametric regression with Weibull distributions. Multivariable models were adjusted for age at diagnosis, gender, race, chemotherapy, radiotherapy, and cancer stage. Results: In the multivariable analysis, the hazard ratio for cetuximab compared to cisplatin or carboplatin/paclitaxel was HR=0.77[95% CI = 0.67, 0.90] in the HPV - group, suggesting more favorable outcomes for the patients on cetuximab in this group. However, in the HPV + cohort, the hazard ratio was 1.88 [95% CI = 1.42, 2.50] for those patients treated with cetuximab vs platinum-based therapy. Conclusions: Our data suggest that cetuximab may have inferior outcomes in HPV-associated OPSCC compared to traditional platinum-based therapy.
Language	English
Publishing date	2017-09-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.20197
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Article: Apoptosis: a key in neurodegenerative disorders.

Ekshyyan, Oleksandr / Aw, Tak Yee

Current neurovascular research

2005 Volume 1, Issue 4, Page(s) 355–371

Abstract: Apoptosis is an important process in the development of the nervous system. Typically, approximately 50% of the neurons apoptose during neurogenesis before the nervous system matures. However, recent paradigms implicate premature apoptosis and/or ... ...

Abstract	Apoptosis is an important process in the development of the nervous system. Typically, approximately 50% of the neurons apoptose during neurogenesis before the nervous system matures. However, recent paradigms implicate premature apoptosis and/or aberrations in the fine control of neuronal apoptosis in the pathogenesis of a variety of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, stroke, brain trauma, spinal cord injury, and diabetic neuropathy. This review will focus on the current concepts salient to understanding the apoptosis death program, the mediators and control of cellular apoptosis, and the relationship between aberrant apoptosis and genesis of neurodegenerative disorders. The discussion will also highlight current advances in methodology, such as utilization of neuronal cell lines and mutant animal models, in investigations of neuronal apoptotic death. The knowledge of apoptosis mechanisms could underpin the basis for development of novel therapeutic strategies and treatment modalities that are directed at control of the neuronal apoptotic death program.
MeSH term(s)	Animals ; Apoptosis ; Humans ; Models, Biological ; Neurodegenerative Diseases/classification ; Neurodegenerative Diseases/pathology
Language	English
Publishing date	2005-09-08
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	2296350-9
ISSN	1567-2026
ISSN	1567-2026
DOI	10.2174/1567202043362018
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Zs.A 6646: Show issues

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Article: Rapamycin targets Interleukin 6 (IL-6) expression and suppresses endothelial cell invasion stimulated by tumor cells.

Ekshyyan, Oleksandr / Khandelwal, Alok R / Rong, Xiaohua / Moore-Medlin, Tara / Ma, Xiaohui / Alexander, Jonathan Steven / Nathan, Cherie-Ann O

American journal of translational research

2016 Volume 8, Issue 11, Page(s) 4822–4830

Abstract: mTOR inhibitors have potent antiangiogenic and anti-lymphangiogenic effects in addition to their growth inhibitory effects in head and neck squamous cell carcinoma (HNSCC). Lymphatogenous spread is much more predominant in HNSCC than hematogenous spread ... ...

Abstract	mTOR inhibitors have potent antiangiogenic and anti-lymphangiogenic effects in addition to their growth inhibitory effects in head and neck squamous cell carcinoma (HNSCC). Lymphatogenous spread is much more predominant in HNSCC than hematogenous spread and significantly decreases survival. In this study we evaluated the effects of rapamycin on targeting tumor-stroma crosstalk in HNSCC. HNSCC tumor cells (FaDu) and human lymphatic endothelial cells (HMEC-1A) were co-cultured in various combinations using transwell cell culture inserts to study tumor-stroma crosstalk and the effects of mTOR inhibitor rapamycin. Levels of growth factors and cytokines in cell culture media were measured using Milliplex bead immunoassay (EMD Millipore) and ELISA assay (R&D Systems). We found that conditioned media collected from tumor cells or co-culture with tumor cells significantly increased the invasiveness of lymphatic and blood vascular endothelial cells (
Language	English
Publishing date	2016-11-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2471058-1
ISSN	1943-8141
ISSN	1943-8141
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Article: Apoptosis in acute and chronic neurological disorders.

Ekshyyan, Oleksandr / Aw, Tak Yee

Frontiers in bioscience : a journal and virtual library

2004 Volume 9, Page(s) 1567–1576

Abstract: Programmed cell death or apoptosis is a physiologically important process in neurogenesis wherein approximately 50% of the neurons apoptose during maturation of the nervous system. However, premature apoptosis and/or aberrations in apoptosis control ... ...

Abstract	Programmed cell death or apoptosis is a physiologically important process in neurogenesis wherein approximately 50% of the neurons apoptose during maturation of the nervous system. However, premature apoptosis and/or aberrations in apoptosis control contribute to the pathogenesis of a variety of neurological disorders including acute brain injury such as trauma, spinal cord injury, ischemic stroke and ischemia/reperfusion as well as chronic disease states such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, spinal muscular atrophy, and diabetic neuropathy. The current review will focus on two major topics, namely, the general concepts of our current understanding of the apoptosis death machinery, its mediators and regulation, and the relationship between aberrant apoptosis and genesis of neurodegenerative disorders. This knowledge of apoptosis mechanisms will underpin the basis for development of novel therapeutic strategies and treatment modalities that are directed at control of the neuronal apoptotic death program.
MeSH term(s)	Acute Disease ; Animals ; Apoptosis ; Brain Ischemia/pathology ; Caspases/metabolism ; Chronic Disease ; Humans ; Mice ; Nervous System Diseases/metabolism ; Nervous System Diseases/pathology ; Neurodegenerative Diseases/pathology ; Signal Transduction ; Stroke/pathology
Chemical Substances	Caspases (EC 3.4.22.-)
Language	English
Publishing date	2004-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	2141320-4
ISSN	1093-9946
ISSN	1093-9946
DOI	10.2741/1357
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Zs.A 5867: Show issues

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Article ; Online: EBV and not HPV sensitizes tobacco-associated head and neck cancer cell line FaDu to radiotherapy.

Anandharaj, Arunkumar / Ekshyyan, Oleksandr / Jia, Yali / Rong, Xiaohua / Harrison, Lynn / Shi, Runhua / Scott, Rona S / Nathan, Cherie-Ann O

Acta oto-laryngologica

2016 Volume 136, Issue 4, Page(s) 354–362

Abstract: Conclusion EBV radiosensitized the p53 mutant tobacco associated head and neck cell line, FaDu. Objectives In the head and neck, HPV is a major risk factor associated with tonsil and base of tongue cancers, while a majority of undifferentiated ... ...

Abstract	Conclusion EBV radiosensitized the p53 mutant tobacco associated head and neck cell line, FaDu. Objectives In the head and neck, HPV is a major risk factor associated with tonsil and base of tongue cancers, while a majority of undifferentiated nasopharyngeal cancers are positive for EBV. Clinically, head and neck tumors positive for HPV or EBV are more radiosensitive than tumors associated with tobacco and alcohol. This study aimed to evaluate whether viral infections can sensitize tobacco-associated head and neck squamous cell carcinoma cell line that harbors multiple mutations, especially TP53, to radiotherapy. Method Four FaDu cell lines (vector control - FaDu-DN; FaDu expressing HPV16 E6/E7 - FaDu-HPV; FaDu infected with EBV - FaDu-EBV; and FaDu-HPV infected with EBV - FaDu-HE) were evaluated for their radiation sensitivity using clonogenic assay. Cell cycle, protein expression, apoptosis, and cellular senescence were analyzed. Results FaDu-EBV and FaDu-HE exhibited significantly increased radiosensitivity in comparison with the control cell line. Radiation-induced cell cycle arrest was altered in all cell lines expressing viral genes. The observed distribution of cells at G1 and S phases was associated with a significant increase in expression of p21 protein along with decreased levels of pAKT/AKT and pERK/ERK ratio (p < 0.05) and increased cellular senescence (p < 0.05).
MeSH term(s)	Apoptosis/radiation effects ; Carcinoma, Squamous Cell/radiotherapy ; Carcinoma, Squamous Cell/virology ; Cell Cycle/radiation effects ; Cell Line, Tumor ; Epstein-Barr Virus Infections/complications ; Genes, Viral ; Head and Neck Neoplasms/radiotherapy ; Head and Neck Neoplasms/virology ; Humans ; Male ; MicroRNAs/metabolism ; Middle Aged ; Oncogenes ; Papillomavirus Infections/complications ; RNA, Viral/metabolism ; Tobacco Use/adverse effects
Chemical Substances	MicroRNAs ; RNA, Viral
Language	English
Publishing date	2016
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1651-2251
ISSN (online)	1651-2251
DOI	10.3109/00016489.2015.1114182
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Article ; Online: Photopreventive Effect and Mechanism of AZD4547 and Curcumin C3 Complex on UVB-Induced Epidermal Hyperplasia.

Khandelwal, Alok R / Rong, Xiaohua / Moore-Medlin, Tara / Ekshyyan, Oleksandr / Abreo, Fleurette / Gu, Xin / Nathan, Cherie-Ann O

Cancer prevention research (Philadelphia, Pa.)

2016 Volume 9, Issue 4, Page(s) 296–304

Abstract: Aggressive cutaneous squamous cell carcinoma (cSCC) of the skin is the second most common type of skin cancer in the United States due to high exposure to ultraviolet B (UVB) radiation. In our previous studies, Curcumin C3 complex (C3), a standardized ... ...

Abstract	Aggressive cutaneous squamous cell carcinoma (cSCC) of the skin is the second most common type of skin cancer in the United States due to high exposure to ultraviolet B (UVB) radiation. In our previous studies, Curcumin C3 complex (C3), a standardized preparation of three curcumonoids, delayed UVB-induced tumor incidence and inhibited multiplicity. Exposure to UVB activates mTOR and FGFR signaling that play a key role in skin tumorigenesis. The purpose of this study was to investigate the efficacy of C3 complex to afford protection against acute UVB-induced hyperproliferation by targeting the mTOR and FGFR signaling pathways. Pretreatment with C3 complex significantly inhibited UVB-induced FGF-2 induction, FGF-2-induced cell proliferation, progression and colony formation, mTORC1 and mTORC2 activation, and FGFR2 phosphorylation in the promotion-sensitive JB6 cells epithelial cells. Further, FGFR was critical for UVB-induced mTOR activation, suggesting an important role of FGFR2 in UVB-induced mTOR signaling. SKH-1 mice pretreated with C3 (15 mg/kg/b.w.) for 2 weeks followed by a single exposure to UVB (180 mj/cm(2)) significantly attenuated UVB-induced mTORC1, mTORC2, and FGFR2 activation. To further assess the role of FGFR in UVB-induced hyperproliferation, SKH-1 mice were pretreated with AZD4547 (5 mg/kg/b.w.); a selective pan-FGFR kinase inhibitor followed by single exposure to UVB (180 mj/cm(2)). AZD4547 significantly inhibited UVB-induced mTORC1 and mTORC2 activation, epidermal hyperplasia and hyperproliferation. Our studies underscore the importance of FGFR signaling in UVB-induced acute skin changes and the role of FGFR/mTOR signaling in mediating the effects of C3 complex in the pathogenesis of skin cancer.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Benzamides/pharmacology ; Carcinoma, Squamous Cell/prevention & control ; Cell Line ; Cell Proliferation/drug effects ; Cell Proliferation/radiation effects ; Curcumin/pharmacology ; Epidermis/drug effects ; Epidermis/radiation effects ; Female ; Fibroblast Growth Factor 2/blood ; Fibroblast Growth Factor 2/metabolism ; Humans ; Hyperplasia ; Mechanistic Target of Rapamycin Complex 1 ; Mechanistic Target of Rapamycin Complex 2 ; Mice ; Mice, Hairless ; Multiprotein Complexes/metabolism ; Phosphorylation ; Piperazines/pharmacology ; Protein Kinase Inhibitors/pharmacology ; Pyrazoles/pharmacology ; Receptor, Fibroblast Growth Factor, Type 2/metabolism ; Signal Transduction ; Skin Neoplasms/prevention & control ; TOR Serine-Threonine Kinases/metabolism ; Ultraviolet Rays/adverse effects
Chemical Substances	AZD4547 ; Antineoplastic Agents ; Benzamides ; Multiprotein Complexes ; Piperazines ; Protein Kinase Inhibitors ; Pyrazoles ; Fibroblast Growth Factor 2 (103107-01-3) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Fgfr2 protein, mouse (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 2 (EC 2.7.10.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Mechanistic Target of Rapamycin Complex 2 (EC 2.7.11.1) ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2016-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2434717-6
ISSN	1940-6215 ; 1940-6207
ISSN (online)	1940-6215
ISSN	1940-6207
DOI	10.1158/1940-6207.CAPR-15-0366
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Zs.A 6766: Show issues

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Article ; Online: 18F-fluorodeoxythymidine micro-positron-emission tomography versus 18F-fluorodeoxyglucose micro-positron-emission tomography for in vivo minimal residual disease imaging.

Ekshyyan, Oleksandr / Sibley, Don / Caldito, Gloria C / Sunderland, John / Vascoe, Chris / Nathan, Cherie-Ann O

The Laryngoscope

2012 Volume 123, Issue 1, Page(s) 107–111

Abstract: Objectives/hypothesis: The early detection of persistent/recurrent disease of head and neck squamous cell carcinoma (HNSCC) after treatment can be challenging. The currently used radioisotope (18)F-fluorodeoxyglucose (FDG) is a nonspecific tracer for ... ...

Abstract	Objectives/hypothesis: The early detection of persistent/recurrent disease of head and neck squamous cell carcinoma (HNSCC) after treatment can be challenging. The currently used radioisotope (18)F-fluorodeoxyglucose (FDG) is a nonspecific tracer for cancer cells as it detects all metabolically active cells including inflammation. (18)F-fluorodeoxythymidine (FLT) is a radioactive tracer for rapidly proliferating cells, and therefore is more specific for detecting cancer. Our aim was to compare FLT and FDG microPET (positron-emission tomography) to the gold standard in vivo bioluminescence imaging for serial assessment of neoplastic growth in a minimal residual disease in vivo model. Study design: Prospective outcomes research. Methods: In order to mimic the postsurgical environment of HNSCC patients FaDu cells transfected with a luciferase-expressing retrovirus were inoculated into the skin flap of Balb/c nu/nu mice. Three days later before tumors formed, mice were randomized into (18)F-FLT or (18) F-FDG groups, and microPET imaging was performed on days 3, 6, 10, 18, and 24 after tumor cell inoculation. Results: (18)F-FLT detected tumors as early as day 3 even before tumors were palpable, whereas (18)F-FDG only detected palpable tumors. The average overall normalized radioactivity in the FLT group was significantly higher than the FDG group (P = .025). Conclusions: (18)F-FLT identified tumor cells before tumors were palpable and can potentially be used for early detection of persistence/recurrence of HNSCC. In addition, this radioisotope can be used to monitor adjuvant therapy with novel targeted therapeutics in preclinical models of persistent disease.
MeSH term(s)	Animals ; Carcinoma, Squamous Cell/diagnostic imaging ; Dideoxynucleosides ; Fluorine Radioisotopes ; Fluorodeoxyglucose F18 ; Head and Neck Neoplasms/diagnostic imaging ; Luminescent Measurements/methods ; Mice ; Mice, Nude ; Neoplasm, Residual/diagnostic imaging ; Positron-Emission Tomography/methods ; Prospective Studies ; Squamous Cell Carcinoma of Head and Neck ; Xenograft Model Antitumor Assays
Chemical Substances	Dideoxynucleosides ; Fluorine Radioisotopes ; Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2012-09-27
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80180-x
ISSN	1531-4995 ; 0023-852X
ISSN (online)	1531-4995
ISSN	0023-852X
DOI	10.1002/lary.23600
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Article ; Online: Serum biomarkers in head and neck squamous cell cancer.

Kaskas, Nadine M / Moore-Medlin, Tara / McClure, Gloria B / Ekshyyan, Oleksandr / Vanchiere, John A / Nathan, Cherie-Ann O

JAMA otolaryngology-- head & neck surgery

2014 Volume 140, Issue 1, Page(s) 5–11

Abstract: Importance: Serum biomarkers may be useful in the evaluation of suspected head and neck squamous cell cancer (HNSCC) and as indicators of treatment success or failure in adjuvant and chemopreventive clinical trials.: Objective: To determine serum ... ...

Abstract	Importance: Serum biomarkers may be useful in the evaluation of suspected head and neck squamous cell cancer (HNSCC) and as indicators of treatment success or failure in adjuvant and chemopreventive clinical trials. Objective: To determine serum cytokine and chemokine concentrations altered in patients with HNSCC compared with healthy volunteers to identify potential biomarkers. Design, setting, and participants: A retrospective experimental laboratory study at Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport. Serum samples from 50 patients with stages II, III, and IV HNSCC and 20 healthy volunteers were available for study. Primary tumor sites represented in the patient group included the nasal cavity, oral cavity, oropharynx, hypopharynx, and larynx. Interventions: Following institutional review approval and written informed consent, blood samples were drawn from patients. No intervention, to include any kind of diagnostic workup or treatment, was provided to patients during the course of this study. Main outcomes and measures: The main outcome measures were the quantification of cytokine and chemokine concentrations in serum samples. Luminex multiplex panel technology was used for simultaneous measurement of 18 analytes, including fibroblast growth factor 2, granulocyte-macrophage colony-stimulating factor, growth-related oncogene, interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, inducible protein (IP)-10, soluble CD40 ligand, tumor necrosis factor, and vascular endothelial growth factor. Results: The serum samples of patients with HNSCC contained lower levels of IFN-γ (mean patient serum level, 6.08 pg/mL, compared with the mean control level, 26.20 pg/mL; P = .004), IL-13 (mean patient serum level, 2.85 pg/mL, compared with the control mean level, 7.23 pg/mL; P = .02), and macrophage inflammatory protein-1β (MIP-1β) (mean patient serum level, 14.91 pg/mL, compared with the mean control level, 28.98 pg/mL; P = .004), and elevated levels of IP-10 (mean patient serum level, 359.24 pg/mL, compared with mean control level, 216.40 pg/mL; P = .04). All other markers tested were not significantly different between patients with cancer and controls. Conclusions and relevance: This pilot study demonstrated a significant decrease in serum IFN-γ, IL-13, and MIP-1β levels and a significant elevation of serum IP-10 concentration in patients with HNSCC, irrespective of primary tumor site. If validated in larger, independent studies, these serum biomarkers may be useful in the diagnosis and treatment of HNSCC. In the future, a defined, multianalyte screening panel could facilitate early diagnosis of HNSCC, allowing for earlier treatment and thereby reducing patient mortality.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood ; Carcinoma, Squamous Cell/blood ; Carcinoma, Squamous Cell/pathology ; Case-Control Studies ; Chemokines/blood ; Cytokines/blood ; Female ; Head and Neck Neoplasms/blood ; Head and Neck Neoplasms/pathology ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Pilot Projects ; Retrospective Studies
Chemical Substances	Biomarkers, Tumor ; Chemokines ; Cytokines
Language	English
Publishing date	2014-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701825-8
ISSN	2168-619X ; 2168-6181
ISSN (online)	2168-619X
ISSN	2168-6181
DOI	10.1001/jamaoto.2013.5688
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