Effects of stress and stress-related mediators on the carcinogenesis and head neck cancer progression

• Grant number: 16/25255-0
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2017
• End date: June 30, 2019
• Field of knowledge: Health Sciences - Dentistry - Oral and Maxillofacial Surgery
• Principal Investigator: Daniel Galera Bernabé
• Grantee: Daniel Galera Bernabé
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Associated researchers: Dulce Elena Casarini ; Gisele Zoccal Mingoti ; Glauco Issamu Miyahara ; Sandra Helena Penha de Oliveira

Abstract

A long time ago it has been hypothesized that emotional factors can influence the cancer development. However, only in the last decade investigations have showed more consistently that emotional stress and their hormones may affect cancer progression. Nevertheless, the influence of the emotional and neurohormonal factors on carcinogenesis remains unclear. The head and neck cancer (HNC) is a disease with high morbidity and mortality and its main risk factors are the smoking and alcoholism. Little is known regarding the effects of the stress and their neurohormones on carcinogenesis in preclinical models and on the HNC progression in humans. In this project we will use in vitro and animal models, as well a clinical study to investigate the impact of the stress and stress-related hormonones on carcinogenesis and HNC prognosis. In the in-vitro study, the influence of stress hormones (cortisol and norepinephrine) on the DNA damage and malignant transformation will be investigated by the molecular biology assays. In the pre-clinical study will be analyzed the influence of early life stress on induced-4NQO oral carcinogenesis in rats. Anxiety-like behavior tests will be conducted in order to assess behavioral changes during the carcinogenesis process. The oral squamous cell carcinoma (OSCC) incidence (by microscopy) and the tumor progression-related genes expression (by real time PCR) will be analyzed. To evaluate the influence of the stress on the endorine profile in microenviroment, hormones and cytokines concentrations in tumor tissue will be investigated by multiplex immunoassay. Neuronal activation in brain regions associated with anxiety will be evaluated by immunohistochemistry. Finally, we will drive a clinical investigation in which the psychological anxiety levels, and the plasma levels of stress-related hormones will be measured in oral and oropharyngeal cancer by High-performance liquid chromatograph (HPLC) and immunoassays. Statistical tests will be used to evaluate the correlation between emotional measures and hormonal plasma levels, their association with clinicopathological variables and their influence on prognostic factors. We hope the present study can uncover new biological parameters that affect the onset and HNC progression. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VERZA, FLAVIA ALVES; VALENTE, VITOR BONETTI; OLIVEIRA, LIA KOBAYASHI; KAYAHARA, GISELI MITSUY; CRIVELINI, MARCELO MACEDO; FURUSE, CRISTIANE; BIASOLI, EDER RICARDO; MIYAHARA, GLAUCO ISSAMU; OLIVEIRA, SANDRA HELENA PENHA; BERNABE, DANIEL GALERA. Social isolation stress facilitates chemically induced oral carcinogenesis. PLoS One, v. 16, n. 1, JAN 7 2021. (16/25255-0)

TJIOE, KELLEN CRISTINE; CARDOSO, DIOVANA MELO; OLIVEIRA, SANDRA HELENA PENHA; BERNABE, DANIEL GALERA. Stress hormone norepinephrine incites resistance of oral cancer cells to chemotherapy. Endocrine-Related Cancer, v. 29, n. 4, p. 12-pg., 2022-04-01. (16/25255-0, 16/00051-2)

BASTOS, DANIELA B.; SARAFIM-SILVA, BRUNA A. M.; SUNDEFELD, MARIA LUCIA M. M.; RIBEIRO, AMANDA A.; BRANDAO, JULIANA D. P.; BIASOLI, EDER R.; MIYAHARA, I, GLAUCO; CASARINI, DULCE E.; BERNABE, DANIEL G.. Circulating catecholamines are associated with biobehavioral factors and anxiety symptoms in head and neck cancer patients. PLoS One, v. 13, n. 8, AUG 20 2018. (16/25255-0, 15/12485-4, 10/51904-9)

BERTOLINI BOTELHO, MARIA CLARA; ANGELO CINTRA, LUCIANO TAVARES; DA SILVA, CRISTIANE CANTIGA; KAYAHARA, GISELI MITSUY; PEREIRA, ROSANI BELZUNCES; OLIVEIRA SANTOS, MYLENA FERNANDA; MIYAHARA, GLAUCO ISSAMU; BIASOLI, EDER RICARDO; PENHA OLIVEIRA, SANDRA HELENA; BERNABE, DANIEL GALERA. Early life stress exacerbates bone resorption and inhibits anxiety-like behaviour induced by apical periodontitis in rats. International Endodontic Journal, v. 56, n. 2, p. 10-pg., 2022-11-23. (16/25255-0)

SHIBUYA, CAROLINE MIHO; TJIOE, KELLEN CRISTINE; PENHA OLIVEIRA, SANDRA HELENA; BERNABE, DANIEL GALERA. Propranolol inhibits cell viability and expression of the pro-tumorigenic proteins Akt, NF-KB, and VEGF in oral squamous cell carcinoma. ARCHIVES OF ORAL BIOLOGY, v. 136, p. 9-pg., 2022-04-01. (16/25255-0, 16/00051-2, 17/18650-2)

VALENTE, VITOR BONETTI; DE MELO CARDOSO, DIOVANA; KAYAHARA, GISELI MITSUY; NUNES, GIOVANA BARROS; TJIOE, KELLEN CRISTINE; BIASOLI, EDER RICARDO; MIYAHARA, GLAUCO ISSAMU; OLIVEIRA, SANDRA HELENA PENHA; MINGOTI, GISELE ZOCCAL; BERNABE, DANIEL GALERA. Stress hormones promote DNA damage in human oral keratinocytes. SCIENTIFIC REPORTS, v. 11, n. 1, OCT 5 2021. (17/07784-8, 16/25255-0)