RESUMO
Catecholamines, which are involved in response to physical or emotional stress, have emerged as one of the main mediators of the relationship between chronic stress and cancer progression. The study in this issue of Cancer Research by Liu and colleagues reveals a new mechanism by which psychologic stress stimulates cancer progression through the D2 dopamine receptor and activation of the oxygen-independent HIF1α pathway. Although most investigations so far have focused on the action of the stress-related catecholamines norepinephrine and epinephrine on tumor cells, this study shows that dopamine and its receptor can be a potential therapeutic target. The findings broaden the understanding of the interaction of catecholamines with the tumor microenvironment and reinforces the need to look at psychologic stress as a modulator of cancer progression.See related article by Liu et al., p. 5353.
Assuntos
Catecolaminas , Neoplasias , Dopamina , Epinefrina , Norepinefrina , Estresse PsicológicoRESUMO
Studies have shown that stress-related catecholamines may affect cancer progression. However, little is known about catecholamine secretion profiles in head and neck cancer patients. The present study investigated plasma norepinephrine and epinephrine levels in head and neck squamous cell carcinoma (HNSCC) patients and patients with oral leukoplakia, as well as their association with clinicopathological and biobehavioral variables and anxiety symptoms. A total of 93 patients with HNSCC and 32 patients with oral leukoplakia were included. Plasma norepinephrine and epinephrine levels were measured by high performance liquid chromatography with electrochemical detection (HPLC-ED), and psychological anxiety levels were measured by the Beck Anxiety Inventory (BAI). Plasma norepinephrine and epinephrine concentrations were significantly higher in patients with oral and oropharyngeal squamous cell carcinoma (SCC) compared to non-cancer patients. Oral SCC patients displayed plasma norepinephrine levels about six times higher than oropharyngeal SCC patients, and nine times higher than oral leukoplakia patients (p < .001). Plasma epinephrine levels in oral SCC patients were higher compared to the oropharyngeal SCC (p = .0097) and leukoplakia (p < .0001) patients. Oropharyngeal SCC patients had higher plasma norepinephrine (p = .0382) and epinephrine levels (p = .045) than patients with oral leukoplakia. Multiple regression analyses showed that a history of high alcohol consumption was predictive for reduced plasma norepinephrine levels in the oral SCC group (p < .001). Anxiety symptom of "hand tremor" measured by the BAI was an independent predictor for higher plasma norepinephrine levels in HNSCC patients (ß = 157.5, p = .0377), while the "heart pounding/racing" symptom was independently associated with higher plasma epinephrine levels in the oropharyngeal SCC group (ß = 15.8, p = .0441). In oral leukoplakia patients, sleep deprivation and worse sleep quality were independent predictors for higher plasma norepinephrine levels, while severe tobacco consumption and higher anxiety levels were factors for higher plasma epinephrine levels. These findings suggest that head and neck cancer patients display sympathetic nervous system hyperactivity, and that changes in circulating catecholamines may be associated with alcohol consumption, as well as withdrawal-related anxiety symptoms.
Assuntos
Ansiedade/sangue , Catecolaminas/sangue , Leucoplasia Oral/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Adulto , Idoso , Ansiedade/complicações , Ansiedade/patologia , Epinefrina/sangue , Feminino , Humanos , Leucoplasia Oral/patologia , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Sistema Nervoso Simpático/patologia , Tremor/sangue , Tremor/fisiopatologiaRESUMO
BACKGROUND: Oral lichenoid reactions (OLRs) have been rarely reported in pediatric patients. CASE REPORT: This article reports an unusual case of a 15-year-old girl who had white plaques in tongue and buccal mucosa oral which initially were diagnosed as oral lichen planus (OLP). At first, the patient and her family denied systemic or local medication use. Biopsy was performed, and histopathological aspects were suggestive of OLP. Despite the attempt of treatment with topical corticoid, the lesions did not recede. Patient's behavior and medical history were again investigated and revealed that she had been using almost daily in her school an artificially colored and flavored lollipop. One week after removing lollipop use behavior, the oral lesions showed complete resolution and OLR diagnosis was defined. CONCLUSION: The present case denotes that OLR should be considered in the differential diagnosis of oral white plates in children and artificially colored sweets can be its causal agent.
Assuntos
Doces/efeitos adversos , Líquen Plano Bucal/diagnóstico , Administração Tópica , Adolescente , Biópsia , Diagnóstico Diferencial , Feminino , Glucocorticoides/administração & dosagem , Humanos , Mucosa Bucal , LínguaRESUMO
Patients with oral cancer can have high psychological distress levels, but the effects of stress-related hormones on oral cancer cells and possible mechanisms underlying these relationships are unknown. In this study, we have investigated the effects of stress-related hormones on interleukin-6 (IL-6) secretion and proliferation of oral squamous cell carcinoma (OSCC) cells. The effects of norepinephrine (NE), and cortisol were studied in SCC9, SCC15, and SCC25 cells and effects of isoproterenol in SCC9 and SCC25 cells. Real-time PCR studies revealed constitutive ß1- and ß2-adrenergic receptors (ß-ARs) expression in the SCC9, SCC15, and SCC25 cells. The results showed that NE and isoproterenol significantly enhanced IL-6 mRNA expression and protein production in supernatants of SCC9 and SCC25 cells. Physiological stress levels of NE and isoproterenol (10 µM) at 1 h elicited the most robust IL-6 increase. Regarding IL-6 secretion, 10 µM NE induced a 5-fold increase at 1 h, 3.7-fold increase at 6 h, and 3.2-fold at 24 h in SCC9 cells. These effects were blocked by the ß-adrenergic antagonist propranolol, supporting a role for ß-ARs in IL-6 secretion. The effects of cortisol varied according to the hormone concentration. Pharmacological concentrations of cortisol (1000 nM) inhibited IL-6 production by SCC9 and SCC25 cells. Cortisol dose that simulates stress conditions (10 nM) tended to increase IL-6 expression in SCC9 cells. Hormonal doses that simulate stress conditions (10 µM NE, at 6 h in SCC9 and SCC15 cells and 10 nM cortisol, at 48 h in SCC15 cells) stimulated increased cell proliferation. Treatment of SCC9 cells with IL-6 neutralizing ab (10 µg/mL) partially inhibited NE-induced proliferation. Finally, 20 OSCC biopsies were shown to express ß1- and ß2-ARs. These findings suggest that stress hormones can affect oral cancer cells behavior.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Proliferação de Células/efeitos dos fármacos , Hidrocortisona/farmacologia , Interleucina-6/metabolismo , Isoproterenol/farmacologia , Norepinefrina/farmacologia , Análise de Variância , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Humanos , Interleucina-6/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasRESUMO
BACKGROUND: This article reports a rare case of metastasis of salivary duct carcinoma of the parotid gland to the gingiva and reviews the occurrence of metastatic processes to the oral mucosa. METHODS: A 67-year-old white male presented with a chief complaint of a painless nodular tissue growth on the gingiva with reportedly 5 months of evolution. The intraoral examination revealed a reddish, superficially ulcerated nodular lesion ( approximately 2 cm in diameter) on the right mandibular buccal attached gingiva, and the clinical aspect was that of a benign reactive lesion. The patient had undergone a parotidectomy for removal of a salivary duct carcinoma of the parotid gland almost 1 year before. A biopsy of the gingival lesion was performed, and the biopsied tissue was forwarded for histopathologic examination. RESULTS: The analysis of the histopathologic sections of the gingival lesion revealed histomorphologic characteristics very similar to those of the primary parotid gland tumor. The definitive diagnosis was gingival metastasis from a salivary duct carcinoma of the parotid gland. The patient died of complications of a pulmonary metastasis 1 month after the diagnosis of the oral metastatic lesion. CONCLUSIONS: Gingival lesions that mimic reactive and hyperplastic lesions may be metastases from malignant neoplasias of diverse origins. An accurate and timely diagnosis is crucial to establish proper and immediate treatment of the metastatic tumor and possibly identify an occult primary malignant neoplasia.