Sobrevida de pacientes con cáncer gástrico en el Perú, 2009-2010 / Survival rate of patients with stomach cancer in Peru, 2009-2010

OBJETIVO: Determinar la sobrevida de pacientes con diagnóstico de cáncer gástrico en 2009-2010 en el Perú. MÉTODOS: Se realizó un estudio de tipo cohorte retrospectivo de pacientes con diagnóstico de cáncer gástrico registrados en el Sistema Nacional de Vigilancia Epidemiológica (SNVE) de la Dirección General de Epidemiología (DGE) y del Registro de Hechos Vitales (RHV) de la Oficina General de Estadística e Informática (OGEI) para los años 2009-2010. RESULTADOS: Se incluyeron 3 568 pacientes del SNVE, 51,5% eran hombres y 48,5% eran mujeres; la media de edad fue 63,9 años, 60,07% tenían 60 años o más. Se halló que 33,6% tenía adenocarcinoma de tipo intestinal, 18,7% tenía carcinoma de tipo difuso y 4,1% tenía linfoma gástrico primario. La sobrevida global fue de 29,7 ± 0,8 meses y fue mejor para los menores de 60 años (P = 0,034), para las mujeres (P = 0,014) y para el adenocarcinoma de tipo intestinal (P < 0,001). No hubo diferencias (P = 0,713) entre la sobrevida de los pacientes con linfoma gástrico y aquellos con adenocarcinoma. Para evaluar la tasa de mortalidad se incluyeron 6 069 registros de pacientes del RHV, la tasa de mortalidad nacional fue de 10,3 por cada 100 000 habitantes y las regiones con mayor mortalidad fueron Huánuco, Huancavelica y Junín. CONCLUSIONES: La sobrevida general fue de 29,7 ± 0,8 meses, las mujeres, los menores de 60 años y los pacientes con adenocarcinoma de tipo intestinal tienen mejor sobrevida. La mayor mortalidad por cáncer gástrico se concentra en las regiones más pobres del Perú, donde es probable que las condiciones de vida faciliten la alta transmisibilidad de Helicobacter pylori.

OBJECTIVE: Determine the survival rate of patients diagnosed with stomach cancer in 2009-2010 in Peru. METHODS: A retrospective cohort study was conducted of patients diagnosed with stomach cancer registered in the National Epidemiological Surveillance System (SNVE) of the Directorate General of Epidemiology (DGE) and the Register of Vital Statistics (RHV) of the General Office of Statistics and Information (OGEI) for the years 2009-2010. RESULTS: 3 568 patients of the SNVE were included; 51.5% were men and 48.5% were women; the average age was 63.9 years; 60.07% were 60 years old or older. It was found that 33.6% had intestinal type adenocarcinoma, 18.7% had diffuse type carcinoma, and 4.1% had primary gastric lymphoma. The overall survival rate was 29.7 ± 0.8 months and was better for those under 60 years (P = 0.034), for women (P = 0.014) and for intestinal type adenocarcinoma (P< 0.001). There was no difference (P = 0.713) between the survival rate of gastric lymphomas and adenocarcinomas. In order to evaluate mortality, 6 069 patient records from the RHV were included; national mortality was 10.3 per 100 000 population; the regions with the highest mortality were Huánuco, Huancavelica, and Junín. CONCLUSIONS: The general survival rate was 29.7 ± 0.8 months; women, those under 60 years, and patients with intestinal type adenocarcinoma had better survival rates. The highest mortality from stomach cancer is concentrated in the poorest regions of Peru, where it is probable that living conditions facilitate the high communicability of Helicobacter pylori.

Possible Role of Heme Oxygenase-1 and Prostaglandins in the Pathogenesis of Cerebral Malaria: Heme Oxygenase-1 Induction by Prostaglandin D2 and Metabolite by a Human Astrocyte Cell Line

Astrocytes are the most abundant cells in the central nervous system that play roles in maintaining the blood-brain-barrier and in neural injury, including cerebral malaria, a severe complication of Plasmodium falciparum infection. Prostaglandin (PG) D2 is abundantly produced in the brain and regulates the sleep response. Moreover, PGD2 is a potential factor derived from P. falciparum within erythrocytes. Heme oxygenase-1 (HO-1) is catalyzing enzyme in heme breakdown process to release iron, carbon monoxide, and biliverdin/bilirubin, and may influence iron supply to the P. falciparum parasites. Here, we showed that treatment of a human astrocyte cell line, CCF-STTG1, with PGD2 significantly increased the expression levels of HO-1 mRNA by RT-PCR. Western blot analysis showed that PGD2 treatment increased the level of HO-1 protein, in a dose- and time-dependent manner. Thus, PGD2 may be involved in the pathogenesis of cerebral malaria by inducing HO-1 expression in malaria patients.

Suppression of HIV-1 Tat-induced monocyte adhesiveness by a cell-permeable superoxide dismutase in astrocytes

HIV-1 Tat is considered to be one of key players to facilitate monocyte entry into the CNS, which is characteristic feature of AIDS-related encephalitis and dementia. This study was performed to determine the regulatory function of superoxide dismutase (SOD) on the HIV-1 Tat-induced signaling pathways leading to NF-kappaB activation, expression of adhesion molecules, and monocyte adhesion in CRT-MG human astroglioma cells by using cell-permeable SOD. When cell-permeable SOD was added to the culture medium of CRT-MG cells, it rapidly entered the cells in dose- and time-dependent manners. Treatment of astrocytes with cell-permeable SOD led to decrease in Tat-induced ROS generation as well as NF-kappaB activation. Cell-permeable SOD inhibited the activation of MAP kinases including ERK, JNK and p38 by HIV-1 Tat. Treatment of CRT-MG cells with cell-permeable SOD significantly inhibited protein and mRNA levels of ICAM-1 and VCAM-1 up-regulated by HIV-1 Tat, as measured by Western blot analysis and RT-PCR. Furthermore, enhanced adhesiveness of monocyte to astrocyte by HIV-1 Tat was significantly abrogated by pretreatment with cell-permeable SOD fusion proteins. These data indicate that SOD has a regulatory function for HIV-1 Tat-induced NF-kappaB activation in astrocytes and suggest that cell-permeable SOD can be used as a feasible therapeutic agent for regulation of ROS-related neurological diseases.

Increased expression of neuronal nitric oxide synthase in astrocytes and macrophages in the spinal cord of Lewis rats with autoimmune encephalomyelitis

Neuronal nitric oxide synthase (nNOS) is constitutively expressed in neurons of the central nervous system, where it plays a physiological role in neurotransmission. In this study, we examined the functional role of nNOS in experimental autoimmune encephalomyelitis(EAE). The effects of the specific nNOS inhibitor 7-nitroindazole on normal and EAE rats were studied by immunohistochemistry and Western blot analysis. We found that nNOS is constitutively expressed in the spinal cords of normal rats, whilst in the spinal cords of EAE rats, nNOS expression slightly increased, concomitant with the infiltration of T cells and macrophages. Immunohistochemical studies showed that nNOS expression in macrophages and astrocytes increased at the peak stage of EAE and declined thereafter. Treatment with 7-nitroindazole (30 mg/kg) significantly delayed the onset of EAE paralysis, but had no effect on either the incidence or the severity of the paralysis. These findings suggest that nNOs inhibition has a limited role in the induction of rat EAE, and that constitutive nNOS in the spinal cord functions as a novel neurotransmitter, rather than a pro-inflammatory agent.

Isolation and characterization of brain-specific transglutaminases from rat

The relevance of transglutaminases with neural function and several disorders has been emphasized recently. Especially, many polypeptides associated with neurodegenerative diseases are suggested to be putative transglutaminase substrates such as beta amyloid protein of Alzheimer's disease, microtubule-associated proteins and neurofilaments, etc. In addition, the CAG repeated gene products with probable polyglutamine tract, putative transglutaminase substrates, were identified in several neurodegenerative disorders. However, the identity of the brain transglutaminase has not been confirmed, because of enzymic stability and low activity. In the present experiment, we have isolated brain-specific transglutaminases, designated as TGase NI and TGase NII, which are different from other types of transglutaminases in respects of molecular weights (mw. 45 kDa, 29 kDa respectively), substrate affinity, elution profile on ion-exchange chromatography, sensitivity to proteases and ethanol, and immunological properties. The enzymes were localized specifically in the brain tissues but not in the liver tissue. And neural cells such as pheochromocytoma cell, glioma cell, primary neuronal and glial cells were shown to be enriched with TGase NI and TGase NII. The possible biological roles of the enzymes were discussed not only on the aspect of crosslinking activity but also of signal transducing capacity of the enzyme in the brain.

A brain soluble fraction inhibits synaptosomal membrane but not astrocyte ATPase activity

Since a brain soluble fraction (peak II) is known to be able to inhibit synaptosomal membrane Na+, K+-ATPase activity, here we attempted to compare its effect on cellular and subcellular brain components such as synaptosomal and astrocytic membranes, as well as mitochondrial preparations. Peak II highly inhibited total ATPase in synaptosomal membranes but failed to modify enzyme activity in astrocytic and mitochondrial preparations. Findings suggest cellular and subcellular specificity of peak II on brain ATPase activity.