RESUMO
Cervical cancer (CC) is the fourth most common cancer in women worldwide, with more than 500,000 new cases each year and a mortality rate of around 55%. Over 80% of these deaths occur in developing countries. The most important risk factor for CC is persistent infection by a sexually transmitted virus, the human papillomavirus (HPV). Conventional treatments to eradicate this type of cancer are accompanied by high rates of resistance and a large number of side effects. Hence, it is crucial to devise novel effective therapeutic strategies. In recent years, an increasing number of studies have aimed to develop immunotherapeutic methods for treating cancer. However, these strategies have not proven to be effective enough to combat CC. This means there is a need to investigate immune molecular targets. An adaptive immune response against cancer has been described in seven key stages or steps defined as the cancer-immunity cycle (CIC). The CIC begins with the release of antigens by tumor cells and ends with their destruction by cytotoxic T-cells. In this paper, we discuss several molecular alterations found in each stage of the CIC of CC. In addition, we analyze the evidence discovered, the molecular mechanisms and their relationship with variables such as histological subtype and HPV infection, as well as their potential impact for adopting novel immunotherapeutic approaches.
RESUMO
OBJECTIVE: The cyclicity (CIC) of cortisol spontaneously occurs in a minority of patients with Cushing syndrome (CS). When it arises, diagnostic and therapeutic approaches become more challenging. This study aimed to report a patient with Cushing disease (CD) who achieved normalization of cortisol and CIC pattern with pasireotide long-acting release (pasi/LAR). METHODS: A 43-year-old female patient related an 8-month history of CS. An 8-mm pituitary nodule depicted by magnetic resonance imaging, serum cortisol suppression of >50% after 8 mg of dexamethasone therapy, and the absence of other lesions were compatible with a CD diagnosis. The patient presented with a CIC pattern with 1 episode before and 17 episodes after an unsuccessful pituitary surgery. RESULTS: Medical treatment with cabergoline alone up to 3.5 mg/wk and a combined treatment with ketoconazole 400 mg/d did not improve CIC CS. Pasi/LAR was initiated at a dose of 20 mg/mo. A few days after the first dose, the patient experienced symptoms suggestive of adrenal insufficiency. The medication and dose were maintained for 24 months. During this period, there was a normalization of UFC levels and progressive clinical improvement. Additionally, new episodes of CIC were not observed. CONCLUSION: A CD patient with a challenging issue of CIC was reported. The condition was not controlled after pituitary surgery and by the combined treatment with cabergoline and ketoconazole, although hypercortisolism was abated by the continuous use of pasi/LAR. To our knowledge, this is the first report as regards the use of this medication to control CIC in a patient with CD.
RESUMO
The inferior colliculus (IC) is primarily involved in the processing of acoustic stimuli, including those emitted by prey and predators. The role of the central nucleus of the IC (CIC) in fear and anxiety has been suggested based on electrophysiological, behavioral and immunohistochemical studies. The reactivity of high-anxiety rats (HA) to diverse challenges is different from low-anxiety ones (LA). In humans and laboratory animals, pathological anxiety is often accompanied by heightened vigilance and alertness, hyperactivity of the amygdala (AM), and increased amplitude of the auditory evoked potentials (AEP) from the IC. This study aims to evaluate the influence of the inactivation of the central (CEA) and basolateral (BLA) nuclei of the amygdala, after local infusions of the full GABAA agonist muscimol (1nmol/0.2µl), on the AEP elicited in the CIC of rats tested under a learned fear state. Our results showed that both BLA and CEA inactivation change the expression of conditioned fear, in a paradigm using the context as the conditioned stimulus (CS). These changes are correlated to the innate anxiety levels of the animals. It is supposed that this shortcoming is in addition to the imbalance between the regulatory role of the top-down and bottom-up processes in the control of anxiety.
Assuntos
Tonsila do Cerebelo/fisiologia , Ansiedade/fisiopatologia , Ansiedade/psicologia , Medo/fisiologia , Audição/fisiologia , Animais , Condicionamento Psicológico/fisiologia , Potenciais Evocados Auditivos/fisiologia , Agonistas GABAérgicos/farmacologia , Colículos Inferiores/metabolismo , Aprendizagem/fisiologia , Masculino , Microinjeções , Muscimol/farmacologia , Ratos , Ratos Wistar , Ácido gama-Aminobutírico/metabolismoRESUMO
La vitamina A (VA) cumple una función importante sobre el sistema inmunológico demostrándose una relación sinérgica entre estado corporal de VA, y procesos infecciosos. El objetivo fue evaluar la relación entre niveles séricos de retinol y la Citología de Impresión Conjuntival (CIC) con el estado nutricional antropométrico y antecedentes infecciosos en escolares de bajos recursos económicos de una zona urbana de Valencia. Se evaluaron 445 niños (4-13 años de edad), de ambos géneros. Se determinó: retinol sérico (HPLC-r), proteína C reactiva (nefelometría), CIC (ICEPO), los indicadores antropométricos peso-talla (PT) y talla-edad (TE) según referencia nacional y el registro de enfermedades infecciosas (diarrea, enfermedades respiratorias, sarampión y parasitosis) dos meses previos al estudio. El 92,3 por ciento estaban en situación de pobreza, 7 por ciento presentó déficit nutricional (PT ≤ p10), 10,8 por ciento exceso (PT > p90) y 1,5 por ciento talla baja (TE = p3); 18 por ciento de los niños presentó al menos un episodio de diarrea, 39,8 por ciento infección respiratoria superior, 28,1 por ciento inferior y 32,8 por ciento parasitosis. El 10,3 por ciento mostró niveles altos de PCR (> 10 mg/L), el valor promedio de retinol fue 35,7 ± 9,2 μg/dL con una prevalencia de valores bajos (< 20 μg/dL) de 0,7 por ciento, niveles marginales (20-30 μg/dL) de 27,4 por ciento y 9,5 por ciento déficit de VA según CIC. Se encontró correlación significativa entre retinol sérico y CIC y asociación significativa entre retinol sérico y las enfermedades respiratorias superiores únicamente. No se encontró asociación entre los indicadores antropométricos con el estado de vitamina A ni con la morbilidad. No fue posible demostrar la relación entre el estado de vitamina A y los antecedentes infecciosos como diarrea, enfermedades del tracto respiratorio inferior y sarampión, sin embargo, la alta prevalencia de morbilidad y de niveles marginales de VA, hacen que el grupo estudiado...
Vitamin A (VA) is an essential micronutrient for the immune system and several researchs have shown a synergic relationship between vitamin A status and morbidity. The aim was to show the relationship between serum retinol level, Conjunctival Impression Cytology (CIC), anthropometric status, and morbidity in low income school children. 445 children (both genders) between 4 and 13 years old were assessed. Serum retinol levels (HPLC-r), C-reactive protein (nefelometry) and CIC (ICEPO), anthropometric indicators (Weight-height (WH), height-age (HA)according to national references values), morbidity (diarrhea, respiratory tract infections, measles, and parasitosis) two months prior to the evaluation, were determined. The poverty was 92.3%, wasting (WH ≤ p10) 7%, overweight (WH > p90) 10.8%, and stunting (HA = p3) 1.5%. 18% had one or more diarrhea episodes, 39.8% upper respiratory tract infections, 28.1% lower respiratory tract infections, and 32.8% intestinal parasitosis; 10.3% showed ahigh level of C-reactive protein (CRP > 10 mg/L). The average retinol level was 35.7 ± 9.2 μg/dL, with 0.7% low level(< 20 μg/dL), 27.4% of the children at risk of vitamin A deficiency (20-30 μg/dL), and 9.5% deficient according CIC. There was a significant correlation between serum retinol and CIC, and a significant association between serum retinol and upper respiratory tract infections, but not between morbidity and CIC. There was not a significant association between anthropometric indicators and vitamin A status and morbidity. In this study it was not possible to demonstrate the relationship between vitamin A status and diarrhea, measles, lower respiratory tract infections and parasitosis but the high prevalence of marginal serum retinol levels and morbidity in this group makes it susceptible to nutritional surveillance.