Browsing by Subject "head and neck cancer"

Now showing 1 - 5 of 5
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    CERE-120 Prevents Irradiation-Induced Hypofunction and Restores Immune Homeostasis in Porcine Salivary Glands
    (Elsevier, 2020-09-11) Lombaert, Isabelle M. A.; Patel, Vaishali N.; Jones, Christina E.; Villier, Derrick C.; Canada, Ashley E.; Moore, Matthew R.; Berenstein, Elsa; Zheng, Changyu; Goldsmith, Corinne M.; Chorini, John A.; Martin, Daniel; Zourelias, Lee; Trombetta, Mark G.; Edwards, Paul C.; Meyer, Kathleen; Ando, Dale; Passineau, Michael J.; Hoffman, Matthew P.; Oral Pathology, Medicine and Radiology, School of Dentistry
    Salivary gland hypofunction causes significant morbidity and loss of quality of life for head and neck cancer patients treated with radiotherapy. Preventing hypofunction is an unmet therapeutic need. We used an adeno-associated virus serotype 2 (AAV2) vector expressing the human neurotrophic factor neurturin (CERE-120) to treat murine submandibular glands either pre- or post-irradiation (IR). Treatment with CERE-120 pre-IR, not post-IR, prevented hypofunction. RNA sequencing (RNA-seq) analysis showed reduced gene expression associated with fibrosis and the innate and humoral immune responses. We then used a minipig model with CERE-120 treatment pre-IR and also compared outcomes of the contralateral non-IR gland. Analysis of gene expression, morphology, and immunostaining showed reduced IR-related immune responses and improved secretory mechanisms. CERE-120 prevented IR-induced hypofunction and restored immune homeostasis, and there was a coordinated contralateral gland response to either damage or treatment. CERE-120 gene therapy is a potential treatment for head and neck cancer patients to influence communication among neuronal, immune, and epithelial cells to prevent IR-induced salivary hypofunction and restore immune homeostasis.
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    Distribution of the head and neck surgical oncology workforce in the United States
    (Wiley, 2022-11) Talwar, Abhinav; Gordon, Alex J.; Bewley, Arnaud F.; Fancy, Tanya; Lydiatt, William M.; Weed, Donald; Moore, Michael G.; Givi, Babak; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Background The recent trends in education and geographic distribution of the head and neck surgery workforce have not been studied extensively. Methods We reviewed publicly available sources to locate all fellowship-trained head and neck surgeons and recent graduates. The number of surgeons in each state was compared against head and neck cancer incidence data from the Centers for Disease Control. Results The number of graduates increased annually by 1 per 100 000 000 people from 2011–2020. The average number of fellowship-trained surgeons per state was 10 (SD: 12). The average number of new head and neck cancer cases per surgeon was 247 (SD: 135). Ten states (20%) had cases >1 SD above the national average/surgeon, while 3 (6%) had cases >1 SD below the national average. Conclusion Head and neck surgeons are located in most states, but not uniformly. Most states have approximately average density of surgeons; however, several states are outliers.
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    Head and Neck Juxtacortical Chondrosarcoma: A Systematic Review
    (SciTeMed, 2019-03) Jones, Alexander Joseph; Alwani, Mohamedkazim; Summerlin, Don-John; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Objective: To present a case and systematically evaluate trends in clinical presentation, imaging, histopathology, and management modalities and outcomes of all head and neck juxtacortical chondrosarcoma (HNJCS) cases reported in the existing literature. Methods: We describe a rare case of HNJCS from our tertiary referral center following which the PubMed, MEDLINE, Embase, and Web of Science databases were searched for all HNJCS reports. Relevant titles and abstracts were screened. Resulting full-text articles were assessed for eligibility, and remaining studies were included for data extraction, summarization, and analysis. Results: Potential studies were identified dating from May 1946 to February 2019. A total of nine cases were included in our systematic review, eight of which were identified from full-text articles and one recruited from our tertiary referral center. The median presentation age was 41 years with a 66.7% male preponderance. The commonest presenting sign was a painless, isolated swelling after a median symptom duration of 2.5 months. CT imaging revealed hypodense lesions with peripheral enhancement and micro-calcifications. T1-weighted MRI showed hypo- to iso-intense, lobulated masses with peripheral and/or septal enhancement. The masses were diffusely hyper-intense on T2-weighted MRI. Histopathology demonstrated septated lobules of malignant hyaline cartilage with a peripheral fibrous capsule. Most tumors were low- or intermediate-grade tumors with average diameter of 4.3 cm. Local recurrence was identified in only one case (four years after initial resection). No distal and/or nodal metastases were identified. All tumors were managed by wide- or narrow-margin surgical excision. Two reports employed adjuvant treatment. There was no evidence of disease at final follow-up (median of 1.5 years). Conclusion: To the best of our knowledge, only nine cases of HNJCS have been adequately described. HNJCS have relatively consistent clinical and diagnostic profile regardless of location in the body. Surgical management yields excellent outcomes with low recurrence rates.
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    Human papillomavirus oncogenic E6 protein regulates human β-defensin 3 (hBD3) expression via the tumor suppressor protein p53.
    (Impact Journals, 2016-05-10) DasGupta, Twishasri; Nweze, Emeka I.; Yue, Hong; Wang, Liming; Jin, Jessica; Ghosh, Santosh K.; Kawsar, Hameem I.; Zender, Chad; Androphy, Elliot J.; Weinberg, Aaron; McCormick, Thomas S.; Jin, Ge; Department of Dermatology, IU School of Medicine
    Human β-defensin-3 (hBD3) is an epithelial cell-derived innate immune regulatory molecule overexpressed in oral dysplastic lesions and fosters a tumor-promoting microenvironment. Expression of hBD3 is induced by the epidermal growth factor receptor signaling pathway. Here we describe a novel pathway through which the high-risk human papillomavirus type-16 (HPV-16) oncoprotein E6 induces hBD3 expression in mucosal keratinocytes. Ablation of E6 by siRNA induces the tumor suppressor p53 and diminishes hBD3 in HPV-16 positive CaSki cervical cancer cells and UM-SCC-104 head and neck cancer cells. Malignant cells in HPV-16-associated oropharyngeal cancer overexpress hBD3. HPV-16 E6 induces hBD3 mRNA expression, peptide production and gene promoter activity in mucosal keratinocytes. Reduction of cellular levels of p53 stimulates hBD3 expression, while activation of p53 by doxorubicin inhibits its expression in primary oral keratinocytes and CaSki cells, suggesting that p53 represses hBD3 expression. A p53 binding site in the hBD3 gene promoter has been identified by using electrophoretic mobility shift assays and chromatin immunoprecipitation (ChIP). In addition, the p63 protein isoform ΔNp63α, but not TAp63, stimulated transactivation of the hBD3 gene and was co-expressed with hBD3 in head and neck cancer specimens. Therefore, high-risk HPV E6 oncoproteins may stimulate hBD3 expression in tumor cells to facilitate tumorigenesis of HPV-associated head and neck cancer.
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    Pectoralis Major Onlay vs Interpositional Reconstruction Fistulation After Salvage Total Laryngectomy: Systematic Review and Meta-analysis
    (Sage, 2021-05) Cabrera, Claudia I.; Joseph Jones, Alexander; Philleo Parker, Noah; Blevins, Amy E.; Weidenbecher, Mark S.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Objective To evaluate the difference in pharygocutaneous fistula (PCF) development between pectoralis major flap onlay and interpositional reconstructions after salvage total laryngectomy (STL). Data Sources Medline, Cochrane, Embase, Web of Science, CINAHL, and ClinicalTrials.gov. Review Methods A systematic review was performed during January 2020. English articles were included that described minor and major PCF rates after STL reconstructed with pectoralis major onlay or interposition. PCFs were classified as major when conservative therapy was unsuccessful and/or revision surgery was needed. Articles describing total laryngopharyngectomies were excluded. Meta-analyses of the resulting data were performed. Results Twenty-four articles met final criteria amassing 1304 patients. Three articles compared onlay with interposition, and 18 compared onlay with primary closure. Pectoralis interposition demonstrated elevated odds ratio (OR) of PCF formation as compared with onlay (OR, 2.34; P < .001). Onlay reconstruction reduced overall (OR, 0.32; P < .001) and major (OR, 0.21; P < .001) PCF development as compared with primary pharyngeal closure alone. Data were insufficient to compare interposition against primary closure. Conclusions This research shows evidence that pectoralis onlay after STL diminishes the odds of total and major PCF development. Pectoralis interposition reconstruction showed elevated odds of PCF formation as compared with pectoralis onlay.