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J Steroid Biochem Mol Biol ; 199: 105603, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31981799


Calcitriol, the active metabolite of vitamin D, has been widely studied for its preventive and therapeutic activity against several cancers including oral squamous cell carcinoma (OSCC). However, the impact of dietary vitamin D supplementation on initiation and progression of OSCC is unclear. To address this gap in knowledge, we conducted preclinical trials using the 4-nitroquinoline-1-oxide 4NQO carcinogen model of oral carcinogenesis. Female C57BL/6 mice were maintained on one of three vitamin D diets [25 IU, 100 IU, 10,000 IU] and exposed to 4NQO in drinking water for 16 weeks followed by regular water for 10 weeks. Body weight measurements obtained through the study duration did not reveal any differences between the three diets. Animals on 100 IU diet showed lower incidence of high-grade dysplasia/OSCC and higher CD3 + T cells compared to animals on 25 IU and 10,000 IU diets. Serum 25OHD3 levels were highest in animals on 10,000 IU diet at week 0 prior to carcinogen exposure but showed ∼50 % reduction at week 26. Histologic evaluation revealed highest incidence of OSCC in animals maintained on 10,000 IU diet. Animals on 100 IU and 10,000 IU diets showed higher vitamin D receptor VDR and CYP24A1 immunostaining in high-grade dysplastic lesions and OSCC compared to normal tongue. Validation studies performed in a 4NQO-derived OSCC model showed that short-term treatment of animals on a 25 IU diet with calcitriol significantly inhibited tumor growth compared to controls but did not affect tumor growth in animals on reference diet 1000 IU. Collectively, our results highlight the complex dynamics between vitamin D status and oral carcinogenesis. Our observations also suggest that therapeutic benefits of short-term calcitriol treatment may be more pronounced in vitamin D deficient hosts.

Carcinoma de Células Escamosas/dietoterapia , Neoplasias Bucais/dietoterapia , Receptores de Calcitriol/genética , Vitamina D3 24-Hidroxilase/genética , Vitamina D/genética , 4-Nitroquinolina-1-Óxido/toxicidade , Animais , Peso Corporal , Calcitriol/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/patologia , Suplementos Nutricionais/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Humanos , Camundongos , Neoplasias Bucais/sangue , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/patologia , Vitamina D/sangue , Deficiência de Vitamina D/dietoterapia , Deficiência de Vitamina D/genética , Deficiência de Vitamina D/patologia
Int J Telemed Appl ; 2019: 5903106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31186627


Background: Stroke is a leading cause of disability and requires continued care after hospital discharge. Mobile-based interventions are suitable to reduce the cost of stroke rehabilitation and facilitate self-management among stroke survivors. However, before attempting to use mobile-based home exercise program, it is crucial to recognize the readiness of stroke survivors and their caregivers to opt for such interventions. Objective: To assess the acceptability and attitude towards a mobile-based home exercise program among stroke survivors and their primary caregivers. Methods: A cross-sectional study was conducted among 102 participants to understand their attitude and acceptability towards mobile-based home exercise program. A validated 10-item questionnaire was adapted for the study. The questions which assessed the attitude were rated on a three-point Likert scale, with three denoting agree and one denoting disagree. The acceptability was assessed by their willingness to opt for a mobile-based home program services. A Chi-square analysis and cross-tabulation were performed to test differences between caregivers and patients. A logistic regression was performed to determine the effects of age, gender, and mobile phone on acceptability. Results: Ninety-two percent of caregivers and 90% of patients showed willingness to opt for mobile-based intervention. Majority of the participants showed a positive attitude towards this mode of treatment. There was no difference in the attitude noted among caregivers and patients (p>0.05) towards mobile-based intervention. Conclusion: The stroke survivors and caregivers welcomed the concept of mobile-based home exercise program even in a low-resource settings, but further studies to understand treatment and cost-effectiveness of this technology among the stroke survivors would lead to better implementation.

J Oral Pathol Med ; 47(5): 484-491, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29573032


BACKGROUND: The antidiabetic drug metformin (Met) is believed to inhibit tumor proliferation by altering the metabolism of cancer cells. In this study, we examined the effects of Met on tumor oxygenation, metabolism, and growth in head and neck squamous cell carcinoma (HNSCC) using non-invasive multimodal imaging. MATERIALS AND METHODS: Severe combined immunodeficient (SCID) mice bearing orthotopic FaDu HNSCC xenografts were treated with Met (200 mg/kg, ip) once daily for 5 days. Tumor oxygen saturation (%sO2 ) and hemoglobin concentration (HbT) were measured using photoacoustic imaging (PAI). Fluorescence imaging was employed to measure intratumoral uptake of 2-deoxyglucosone (2-DG) following Met treatment while magnetic resonance imaging (MRI) was utilized to measure tumor volume. Correlative immunostaining of tumor sections for markers of proliferation (Ki67) and vascularity (CD31) was also performed. RESULTS: At 5 days post-Met treatment, PAI revealed a significant increase (P < .05) in %sO2 and HbT levels in treated tumors compared to untreated controls. Fluorescence imaging at this time point revealed a 46% decrease in mean 2-DG uptake compared to controls. No changes in hemodynamic parameters were observed in mouse salivary gland tissue. A significant decrease in Ki-67 staining (P < .001) and MR-based tumor volume was also observed in Met-treated tumors compared to controls with no change in CD31 + vessel count following Met therapy. CONCLUSION: Our results provide, for the first time, direct in vivo evidence of Met-induced changes in tumor microenvironmental parameters in HNSCC xenografts. Our findings highlight the utility of multimodal functional imaging for non-invasive mapping of the effects of Met in HNSCC.

Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/metabolismo , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Imagem Multimodal , Animais , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Feminino , Neoplasias de Cabeça e Pescoço/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/patologia , Hemoglobinas/metabolismo , Antígeno Ki-67/metabolismo , Metformina/administração & dosagem , Camundongos SCID , Transplante de Neoplasias , Oxigênio/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral/efeitos dos fármacos