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1.
J Invest Dermatol ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35551922

RESUMO

Altered FGFR signaling has been shown to play a role in a number of cancers. However, the role of FGFR signaling in the development and progression of ultraviolet B-induced (UVB) induced cutaneous squamous cell carcinoma (cSCC) remains unclear. In the current study, the effect of UVB radiation on FGFR activation and its downstream signaling in mouse skin epidermis was examined. In addition, the impact of FGFR inhibition on UVB-induced signaling and skin carcinogenesis was also investigated. Exposure of mouse dorsal skin to UVB significantly increased phosphorylation of FGFRs in the epidermis as well as activation of downstream signaling pathways, including AKT/mTOR, STATs and MAPK. Topical application of the pan-FGFR inhibitor AZD4547 to mouse skin prior to exposure to UVB significantly inhibited FGFR phosphorylation as well as mTORC1, STAT3 and MAPK activation (i.e., phosphorylation). Moreover, AZD4547 pretreatment significantly inhibited UVB-induced epidermal hyperplasia and hyperproliferation and reduced infiltration of mast cells and macrophages into the dermis. AZD4547 treatment also significantly inhibited mRNA expression of inflammatory genes in the epidermis. Finally, mice treated topically with AZD4547 prior to UVB exposure showed decreased cSCC incidence and increased survival rate. Collectively, the current data supports the hypothesis that inhibition of FGFR in epidermis may provide a new strategy to prevent and/or treat UVB-induced cSCC.

3.
Ochsner J ; 22(1): 22-25, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35355641

RESUMO

Background: The United States of America is the leading country in confirmed cases of and deaths from severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19). In April and May 2020, respectively, 0.2% of patients in a Chinese COVID-19-positive cohort and 20.4% of patients in an Italian COVID-19-positive cohort developed cutaneous abnormalities. Cutaneous abnormalities associated with COVID-19 are not well documented or discussed, and investigation of cutaneous manifestations is necessary to determine if they have any clinical value. Methods: We conducted a retrospective study of COVID-19-positive patients who were admitted to Ochsner-Louisiana State University-Shreveport and Ochsner-Louisiana State University-Monroe facilities in Louisiana. Cutaneous manifestations were determined from clinical notes, descriptions in medical records, and a billing code for skin rashes. Results: Of 1,086 COVID-19-positive patients investigated, 871 were African American and 130 were Caucasian. Only 10 patents exhibited probable COVID-19-induced cutaneous abnormalities: 6 (0.7%) of the 871 African American patients and 4 (3.1%) of the 130 Caucasian patients. Dermatologic abnormalities included pruritic or erythematous rash and hypopigmentation of the face, upper chest, abdomen, and trunk areas. Our data are consistent with the smaller percentage of patients in the Chinese cohort study vs the larger percentage in the Italian cohort study. Conclusion: Our data provide evidence that cutaneous manifestations of COVID-19, especially in African American patients, are rare, but documentation of more cases is necessary to establish a cause and effect for COVID-19-induced skin manifestations.

8.
Ear Nose Throat J ; 101(1): 54-58, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32687411

RESUMO

OBJECTIVES: Pneumatic compression garment therapy (PCGT) has been established as treatment for postradiotherapy lymphedema, and its use in head and neck patients is becoming more common. Although effects on interstitial edema of the cervical soft tissues have been studied, effects on internal laryngopharyngeal edema, as well as associated symptoms of dysphagia and dysphonia, have yet to be published. METHODS: We surveyed 7 patients treated with radiation for head and neck cancer (HNC) who had also been prescribed PCGT for cervical lymphedema. Patients were asked about subjective experience with the device, and also administered the Eating Assessment Tool-10 (EAT-10) and Voice Handicap Index-10 (VHI-10) surveys regarding their symptoms after using PCGT. Laryngoscopy videos from these same periods were also reviewed and scored using a validated tool for assessing laryngopharyngeal edema. RESULTS: 85% of patients reported at least some improvement in dysphagia and dysphonia following PCGT. Average EAT-10 score after PCGT was 11.4 and average VHI-10 score after PCGT was 8.7. These compare more favorably to historical scores for the same questionnaires in similar patient populations. Laryngeal edema scores on endoscopic examination were not significantly different after at least 3 months of therapy (pre: 20.15, post: 20.21, P = .975); however, the utility of this result is limited by a low inter-rater reliability (Krippendorff α = .513). CONCLUSIONS: While we are unable to show any difference in objective assessment of laryngopharyngeal edema on endoscopic examination in this small pilot study, patients report substantial subjective improvement in postradiotherapy dysphagia and dysphonia following cervical PCGT that warrants more formal investigation.


Assuntos
Trajes Gravitacionais , Edema Laríngeo/terapia , Doenças Faríngeas/terapia , Radioterapia/efeitos adversos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Disfonia/etiologia , Disfonia/terapia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Hipofaringe , Edema Laríngeo/etiologia , Medidas de Resultados Relatados pelo Paciente , Doenças Faríngeas/etiologia , Projetos Piloto
9.
Mol Carcinog ; 61(1): 33-44, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598317

RESUMO

TP53 is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSCC). Patients with HPV-negative TP53 mutant HNSCC have the worst prognosis, necessitating additional agents for treatment. Since mutant p53 causes sustained activation of the PI3K/AKT/mTOR signaling pathway, we investigated the effect of rapalogs RAD001 and CCI-779 on HPV-negative mutTP53 HNSCC cell lines and xenografts. Rapalogs significantly reduced cell viability and colony formation. Interestingly, rapalogs-induced autophagy with no effect on apoptosis. Pretreatment with autophagy inhibitors, 3-methyladenine (3-MA) and ULK-101 rescued the cell viability by inhibiting rapalog-induced autophagy, suggesting that both RAD001 and CCI-779 induce non-apoptotic autophagy-dependent cell death (ADCD). Moreover, rapalogs upregulated the levels of ULK1 and pULK1 S555 with concomitant downregulation of the mTORC1 pathway. However, pretreatment of cells with rapalogs prevented the ULK-101-mediated inhibition of ULK1 to sustained autophagy, suggesting that rapalogs induce ADCD through the activation of ULK1. To further translate our in vitro studies, we investigated the effect of RAD001 in HPV-negative mutTP53 (HN31 and FaDu) tumor cell xenograft model in nude mice. Mice treated with RAD001 exhibited a significant tumor volume reduction without induction of apoptosis, and with a concomitant increase in autophagy. Further, treatment with RAD001 was associated with a considerable increase in pULK1 S555 and ULK1 levels through the inhibition of mTORC1. 3-MA reversed the effect of RAD001 on FaDu tumor growth suggesting that RAD001 promotes ACDC in HPV-negative mutTP53 xenograft. This is the first report demonstrating that rapalogs promote non-apoptotic ADCD in HPV-negative mutTP53 HNSCC via the ULK1 pathway. Further studies are required to establish the promising role of rapalogs in preventing the regrowth of HPV-negative mutTP53 HNSCC.


Assuntos
Morte Celular Autofágica/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Proteína Supressora de Tumor p53/genética , Animais , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Everolimo/administração & dosagem , Everolimo/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Mutação , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
10.
BMJ Case Rep ; 14(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725062

RESUMO

Substernal goitre is characterised by compressive symptoms of the airway and oesophagus. Chronic, progressive symptoms usually result in surgical removal. We report a rare presentation of substernal goitre in a male in his early 70s who suffered from severe bilateral lower extremity (LE) lymphoedema, resulting in immobility and nursing home placement, and left upper extremity lymphoedema. Our initial assessment led to a filariasis work-up, which was negative, due to the patient's prior 2-year residence in India and service overseas. Chest CT scan revealed an incidental substernal goitre extending posterior to the left innominate vein and aortic arch to the level of the left mainstem bronchus. The patient underwent a left hemithyroidectomy via cervical excision and sternotomy and had an uneventful recovery with resolution of lymphoedema and mobility. Despite extensive literature regarding clinical presentations of substernal goitre, severe lymphoedema of the LE is not a well-established association.


Assuntos
Bócio Subesternal , Edema/etiologia , Bócio Subesternal/complicações , Bócio Subesternal/diagnóstico por imagem , Bócio Subesternal/cirurgia , Humanos , Extremidade Inferior/diagnóstico por imagem , Extremidade Inferior/cirurgia , Masculino , Estudos Retrospectivos , Tireoidectomia
11.
Oral Oncol ; 122: 105578, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34695758

RESUMO

Tobacco exposure and human papillomavirus (HPV) infection are among the main risk factors for the development of head and neck squamous cell carcinoma (HNSCC). Interestingly, recent studies show that tumors from HPV positive (HPV+) smokers and non-smokers have similar mutational profiles, which suggests that HPV could prevent mutation induction or accumulation in the intermediate risk group composed of HPV+ smokers. Hence, we tested this observation by analyzing the effects of 4-Nitroquinoline N-oxide (4NQO), a mutagen and smoking mimetic, in NOK (normal oral keratinocytes), NOKE6.E7 (NOK cells transfected with E6.E7 oncogenes of HPV), HPV+ and HPV negative (HPV-) HNSCC cells. Oxidative DNA damage, γH2AX foci formation, DNA repair protein activation, cell cycle phase analysis, apoptotic cell death, cell viability and clonogenic cell survival were analyzed after 4NQO treatment in NOK, NOKE6.E7, HPV+ and HPV- HNSCC cells. 4NQO increased oxidative base damage and γH2AX foci formation in NOKE6.E7, HPV+ and HPV- HNSCC cells. Phosphorylation of homologous recombination (HR) repair proteins was higher in NOKE6.E7 and HPV+ HNSCC cells compared to NOK and HPV- HNSCC cells respectively. HPV+ and HPV- HNSCC cells showed differential activation of cell cycle regulatory proteins, increased apoptosis, and decreased cell viability upon 4NQO-induced DNA damage. Taken together, 4NQO (a smoking mimetic), induced higher activation of HR repair in HPV+ HNSCC cells compared to HPV- HNSCC cells. This may allow for increased mutational resistance and help explain why HPV+ smokers have a worse prognosis than HPV+ non-smokers.


Assuntos
Reparo do DNA , Neoplasias de Cabeça e Pescoço , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Carcinoma de Células Escamosas de Cabeça e Pescoço , 4-Nitroquinolina-1-Óxido , Células Cultivadas , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Queratinócitos/efeitos dos fármacos , Proteínas E7 de Papillomavirus/genética , Fumar , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
12.
OTO Open ; 5(3): 2473974X211047794, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616997

RESUMO

OBJECTIVE: To evaluate the concerns and needs of patients and survivors of head and neck cancer (HNC) in the COVID-19 era. STUDY DESIGN: Prospective cross-sectional survey. SETTING: Contact lists of 5 North American HNC advocacy groups. METHODS: A 14-question survey was distributed to the contact lists of 5 HNC advocacy groups evaluating patient and survivor needs and concerns related to their cancer care and COVID-19. RESULTS: There were 171 respondents, with 75% in the posttreatment period. The most common concern was contraction of COVID-19 (49%). More patients in active treatment preferred in-person visits than those in the early (≤5 years) and late (>5) survivorship period (72% vs 61% vs 40%, P < .001). A higher percentage of late survivors preferred virtual visits (38% vs 28%, P = .001). In total, 91 (53.2%) respondents sought emotional support outside of immediate family and friends. This included cancer support groups (36.2%), the medical team (29.7%), and other sources outside of these (34.1%), including faith-based organizations and online communities. A higher proportion of women than men (62% vs 41%, P = .001) were seeking emotional support outside of immediate family and friends. CONCLUSIONS: During the early stages of the COVID-19 pandemic, patients with HNC who were actively undergoing treatment had increased need for support resources and preferred in-person provider visits. Alternatively, a higher percentage of patients >5 years from treatment preferred virtual visits. Emotional support outside of family and friends was sought out by a majority of respondents. Further research is needed to determine what support and educational resources are needed to best aid these various populations.

13.
Head Neck ; 43(9): 2698-2704, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34002904

RESUMO

BACKGROUND: The American Joint Committee on Cancer (AJCC) released a new staging system for human papilloma virus (HPV) positive oropharyngeal cancer (OPC) in their eighth edition. The role of smoking in HPV positive oropharyngeal cancer remains controversial and is not factored into the updated staging system. METHODS: Single institutional, retrospective chart review of patients with HPV positive OPC from 2009 to 2017 was completed. Dichotomized smoking data were collected into 0-9 and ≥10 pack-year histories. Kaplan-Meier survival curves compared overall survival (OS) for smokers and nonsmokers. RESULTS: Five-year OS was not statistically different in stage I or stage II HPV positive OPC comparing nonsmokers versus smokers, but worse in stage III smokers (38% vs. 76%, p < 0.05). CONCLUSION: Greater than 10 pack-year smoking status may negatively affect survival in late stage HPV positive OPC but not in early stage disease. HPV positive smokers may require additional risk stratification.


Assuntos
Alphapapillomavirus , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Carcinoma de Células Escamosas/patologia , Humanos , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologia , Papillomaviridae , Infecções por Papillomavirus/patologia , Prognóstico , Estudos Retrospectivos , Fumar/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço
14.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541994

RESUMO

An 86-year-old woman was referred to the otolaryngology clinic for a 1-year history of a painless, slow-growing neck mass. Physical examination showed a fixed, immobile right level II neck mass with normal vocal cord movement. MRI demonstrated a lobulated mass laterally displacing the carotid vessels, consistent with a schwannoma. Despite the pathognomonic radiographic findings for schwannoma, core needle biopsy of the mass was consistent with intramuscular myxoma (IM), which rarely presents in the head and neck region. After multiple years of slow growth with bulging into the pharynx, the patient ultimately underwent surgery to reduce the risk of airway compromise. The location of this IM together with its unusual imaging appearance is a unique finding in the head and neck and adds to the differential diagnoses for neck masses displacing the carotid sheath.


Assuntos
Diagnóstico Diferencial , Neoplasias Musculares , Mixoma/diagnóstico , Mixoma/patologia , Músculos do Pescoço/patologia , Neurilemoma/diagnóstico , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética , Neoplasias Musculares/diagnóstico , Neoplasias Musculares/patologia , Mixoma/cirurgia
15.
BMJ Case Rep ; 14(2)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579799

RESUMO

Ectopic or supernumerary parathyroid tissue has been generally described in the literature in cases found during workup for parathyroid adenoma. We present two unique cases of intratracheal parathyroid gland, a rare occurrence that has not yet been described in the literature. In both cases, the masses were found incidentally and showed no clinical or laboratory evidence of hyperparathyroidism. In both cases, surveillance was chosen as the method of treatment. We present this case series to increase awareness of this potential diagnosis.


Assuntos
Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/fisiopatologia , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/fisiopatologia , Neoplasias das Paratireoides/cirurgia , Traqueia/diagnóstico por imagem , Traqueia/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Resultado do Tratamento
17.
Otolaryngol Head Neck Surg ; 164(2): 234-243, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32660345

RESUMO

OBJECTIVE: The aim of this study was to identify factors that are associated with the occurrence of pneumonia in patients with head and neck cancer (HNC) after treatment. DATA SOURCES: PubMed, Scopus, OVID, and Cochrane Library from inception to November 26, 2019. REVIEW METHODS: A systematic review in accordance with the PRISMA guidelines and an assessment of bias were performed. Included studies reported on the risk factors of pneumonia development after HNC treatment via odds ratios and subdistribution hazard ratios from regression analysis. RESULTS: Fifteen studies were included, comprising 30,962 patients with a mean age of 70 years (range, 19-95 years). Of these, 71.6% are male. The results of our study indicate that the following were independent risk factors contributing to the development of pneumonia: male sex, habitual alcohol consumption, poor oral hygiene before treatment, pretreatment dysphagia, hypopharynx and nasopharynx tumor sites, use of radiotherapy with or without chemotherapy versus surgery alone, addition of chemotherapy to radiotherapy, reirradiation, neck dissection, increased duration of tracheotomy, and use of sedatives for sleeping. CONCLUSION: Multiple patient-, tumor-, and treatment-specific risk factors were identified in predicting pneumonia. Recognition of these risk factors early on may help prevent or at least detect pneumonia in this vulnerable group of patients.


Assuntos
Neoplasias de Cabeça e Pescoço/complicações , Pneumonia/etiologia , Medição de Risco/métodos , Saúde Global , Humanos , Incidência , Pneumonia/epidemiologia , Fatores de Risco
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