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Ermp1 is a putative metalloprotease from Schizosaccharomyces pombe and a member of the Fxna peptidases. Although their function is unknown, orthologous proteins from rats and humans have been associated with the maturation of ovarian follicles and increased ER stress. This study focuses on proposing the first prediction of PPI by comparison of the interologues between humans and yeasts, as well as the molecular docking and dynamics of the M28 domain of Ermp1 with possible target proteins. As results, 45 proteins are proposed that could interact with the metalloprotease. Most of these proteins are related to the transport of Ca2+ and the metabolism of amino acids and proteins. Docking and molecular dynamics suggest that the M28 domain of Ermp1 could hydrolyze leucine and methionine residues of Amk2, Ypt5 and Pex12. These results could support future experimental investigations of other Fxna peptidases, such as human ERMP1.
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This review presents comparative information corresponding to the progress in knowledge of some aspects of infection by the porcine epidemic diarrhea virus (PEDV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronaviruses. PEDV is an alphacoronavirus of great economic importance due to the million-dollar losses it generates in the pig industry. PEDV has many similarities to the SARS-CoV-2 betacoronavirus that causes COVID-19 disease. This review presents possible scenarios for SARS-CoV-2 based on the collected literature on PEDV and the tools or strategies currently developed for SARS-CoV-2 that would be useful in PEDV research. The speed of the study of SARS-CoV-2 and the generation of strategies to control the pandemic was possible due to the knowledge derived from infections caused by other human coronaviruses such as severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). Therefore, from the information obtained from several coronaviruses, the current and future behavior of SARS-CoV-2 could be inferred and, with the large amount of information on the virus that causes COVID-19, the study of PEDV could be improved and probably that of new emerging and re-emerging coronaviruses.
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COVID-19 , Vírus da Diarreia Epidêmica Suína , Humanos , Animais , Suínos , SARS-CoV-2RESUMO
Triple negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis and still lacks a targeted therapy. In this study, we found increased ERK phosphorylation in TNBC cell lines and an important role for ERK in sustaining the migration of TNBC cells. Although ROS have been suggested to have an important role in sustaining MAPK signaling, antioxidant treatment increased ERK phosphorylation, probably suggesting increased invasive potential. Interestingly, treatment with PD0325901 (PD), a MEK inhibitor, decreased ROS levels in TNBC cells and decreased mitochondrial fragmentation in the MDAMB231 cell line. Our data supports an important role for MEK/ERK in TNBC, sustaining cellular migration, regulating mitochondrial dynamics and ROS production in this breast cancer subtype.
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Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Quinases de Proteína Quinase Ativadas por Mitógeno , Proliferação de CélulasRESUMO
Exercise performance and zinc administration individually yield a protective effect on various neurodegenerative models, including ischemic brain injury. Therefore, this work was aimed at evaluating the combined effect of subacute prophylactic zinc administration and swimming exercise in a transient cerebral ischemia model. The prophylactic zinc administration (2.5 mg/kg of body weight) was provided every 24 h for four days before a 30 min common carotid artery occlusion (CCAO), and 24 h after reperfusion, the rats were subjected to swimming exercise in the Morris Water Maze (MWM). Learning was evaluated daily for five days, and memory on day 12 postreperfusion; anxiety or depression-like behavior was measured by the elevated plus maze and the motor activity by open-field test. Nitrites, lipid peroxidation, and the activity of superoxide dismutase (SOD) and catalase (CAT) were assessed in the temporoparietal cortex and hippocampus. The three nitric oxide (NO) synthase isoforms, chemokines, and their receptor levels were measured by ELISA. Nissl staining evaluated hippocampus cytoarchitecture and Iba-1 immunohistochemistry activated the microglia. Swimming exercise alone could not prevent ischemic damage but, combined with prophylactic zinc administration, reversed the cognitive deficit, decreased NOS and chemokine levels, prevented tissue damage, and increased Iba-1 (+) cell number. These results suggest that the subacute prophylactic zinc administration combined with swimming exercise, but not the individual treatment, prevents the ischemic damage on day 12 postreperfusion in the transient ischemia model.
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Natação , Zinco , Animais , Cognição , Isquemia , Aprendizagem em Labirinto , Ratos , Ratos Wistar , Zinco/farmacologiaRESUMO
Cancer is one of the major causes of death in the world and its global burden is expected to continue increasing. In several types of cancers, reactive oxygen species (ROS) have been extensively linked to carcinogenesis and cancer progression. However, studies have reported conflicting evidence regarding the role of ROS in cancer, mostly dependent on the cancer type or the step of the tumorigenic process. We review recent studies describing diverse aspects of the interplay of ROS with cancer in the different stages of cancer progression, with a special focus on their role in carcinogenesis, their importance for cancer cell signaling and their relationship to the most prevalent cancer risk factors.
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Carcinogênese/metabolismo , Progressão da Doença , Neoplasias/metabolismo , Neoplasias/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Animais , Carcinogênese/patologia , Humanos , Fatores de RiscoRESUMO
The taiep rat undergoes hypomyelination and progressive demyelination caused by an abnormal microtubule accumulation in oligodendrocytes, which elicits neuroinflammation and motor behavior dysfunction. Based on taurine antioxidant and proliferative actions, this work explored whether its sustained administration from the embryonic age to adulthood could prevent neuroinflammation, stimulate cell proliferation, promote myelination, and relieve motor impairment. Taurine (50 mg/L of drinking water = 50 ppm) was given to taiep pregnant rats on gestational day 15 and afterward to the male offspring until eight months of age. We measured the levels of nitric oxide (NO), malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), CXCL1, CXCR2 receptor, growth factors (BNDF and FGF2), cell proliferation, and myelin content over time. Integral motor behavior was also evaluated. Our results showed that taurine administration significantly decreased NO and MDA + 4-HDA levels, increased cell proliferation, and promoted myelination in an age- and brain region-dependent fashion compared with untreated taiep rats. Taurine effect on chemokines and growth factors was also variable. Taurine improved vestibular reflexes and limb muscular strength in perinatal rats and fine movements and immobility episodes in adult rats. These results show that chronic taurine administration partially alleviates the taiep neuropathology.
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Destreza Motora , Taurina , Animais , Masculino , Doenças Neuroinflamatórias , Estresse Oxidativo , Ratos , Ratos Mutantes , Ratos Sprague-DawleyRESUMO
Oxygen deprivation in newborns leads to hypoxic-ischemic encephalopathy, whose hallmarks are oxidative/nitrosative stress, energetic metabolism alterations, nutrient deficiency, and motor behavior disability. Zinc and taurine are known to protect against hypoxic-ischemic brain damage in adults and neonates. However, the combined effect of prophylactic zinc administration and therapeutic taurine treatment on intrauterine ischemia- (IUI-) induced cerebral damage remains unknown. The present work evaluated this issue in male pups subjected to transient IUI (10 min) at E17 and whose mothers received zinc from E1 to E16 and taurine from E17 to postnatal day 15 (PND15) via drinking water. We assessed motor alterations, nitrosative stress, lipid peroxidation, and the antioxidant system comprised of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Enzymes of neuronal energetic pathways, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), were also evaluated. The hierarchization score of the protective effect of pharmacological strategies (HSPEPS) was used to select the most effective treatment. Compared with the IUI group, zinc, alone or combined with taurine, improved motor behavior and reduced nitrosative stress by increasing SOD, CAT, and GPx activities and decreasing the GSSG/GSH ratio in the cerebral cortex and hippocampus. Taurine alone increased the AST/ALT, LDH/ALT, and AST/LDH ratios in the cerebral cortex, showing improvement of the neural bioenergetics system. This result suggests that taurine improves pyruvate, lactate, and glutamate metabolism, thus decreasing IUI-caused cerebral damage and relieving motor behavior impairment. Our results showed that taurine alone or in combination with zinc provides neuroprotection in the IUI rat model.
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Glutationa Peroxidase/metabolismo , Isquemia/tratamento farmacológico , Taurina/metabolismo , Zinco/uso terapêutico , Animais , Masculino , Ratos , Zinco/farmacologiaRESUMO
INTRODUCTION: OX40 is an immune checkpoint in cancer and its presence in cancer is a good prognosis, making it a highly relevant target for the development of new immunotherapies. AREAS COVERED: The patent literature reveals vital information on new trends in cancer therapies. The authors used the patent databases of the six major patent offices in the world: United States Patent and Trademark Office, European Patent Office, World Intellectual Property Organization, Japan Patent Office, State Office of Intellectual Property of China and Korean Intellectual Property Office, to generate a panorama of patents related to OX40 agonists. Specific patents have been grouped into innovative patents and adoption patents. EXPERT OPINION: An increasing trend in the development of OX40 agonists in cancer, particularly in the years 2018 and 2019. United States was the leader in generating patents, followed by China and England. Major pharmaceutical companies have at least one anti-OX40 agonist, MEDI6469 and MEDI-0562 (AstraZeneca), PF-04518600 (Pfizer), GSK3174998 (GlaxoSmithKline), BMS-986,178 (Bristol-Myers Squibb) and MOXR0916 (Roche), which represent 68% of clinical trials conducted with OX40 agonists.
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Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Receptores OX40/agonistas , Animais , Desenvolvimento de Medicamentos , Humanos , Imunoterapia , Neoplasias/imunologia , Neoplasias/patologia , Patentes como Assunto , Receptores OX40/imunologiaRESUMO
Introduction: TIM3 and PD-1 are checkpoint inhibitors in cancer that coordinate the downregulation of the proliferation of antigen-specific lymphocytes. There is a great need to discover and develop new therapies focused on inhibiting the action of TIM3 and PD-1 and consequently improving the immune response in the various types of cancer. The authors of patent EP3356411A1 propose several anti-TIM3/anti-PD-1 bispecific antibodies, as well as the method for producing them and their pharmacological application in the treatment of cancer. Areas covered: Patent EP3356411A1 describes a method by producing anti-TIM3/anti-PD-1 bispecific antibodies and their potential in cancer treatment. Expert opinion: Data supporting the patent demonstrate the ability by producing anti-TIM3/anti-PD-1 bispecific antibodies. Although the proposed methodology is very interesting and promising, further studies are necessary to assess the clinical applicability of the inventions on cancer.
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Anticorpos Biespecíficos/administração & dosagem , Imunoterapia/métodos , Neoplasias/terapia , Animais , Anticorpos Biespecíficos/imunologia , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Neoplasias/imunologia , Patentes como Assunto , Receptor de Morte Celular Programada 1/imunologiaRESUMO
Due to their crucial role in cell metabolism and homeostasis, alterations in mitochondrial biology and function have been related to the progression of diverse diseases including cancer. One of the consequences associated to mitochondrial dysfunction is the production of reactive oxygen species (ROS). ROS are known to have a controversial role during cancer initiation and progression and although several studies have tried to manipulate intracellular ROS levels using antioxidants or pro-oxidation conditions, it is not yet clear how to target oxidation for cancer therapy. In this study, we found differences in mitochondrial morphology in breast cancer cells when compared to a non-tumorigenic cell line and differences in mitochondrial function among breast cancer subtypes when exploring gene-expression data from the TCGA tumor dataset. Interestingly, we found increased ROS levels in triple negative breast cancer (TNBC) cell lines and a dependency on ROS for survival since antioxidant treatment induced cell death in TNBC cells but not in an estrogen receptor positive (ER+) cell line. Moreover, we identified the mitochondria as the main source of ROS in TNBC cell lines. Our results indicate a potential use for ROS as a target for therapy in the TNBC subtype which currently has the worst prognosis among all breast cancers and remains as the only breast cancer subtype which lacks a targeted therapy.
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In the cerebral hypoxia-ischemia rat model, the prophylactic administration of zinc can cause either cytotoxicity or preconditioning effect, whereas the therapeutic administration of selenium decreases the ischemic damage. Herein, we aimed to explore whether supplementation of low doses of prophylactic zinc and therapeutic selenium could protect from a transient hypoxic-ischemic event. We administrated zinc (0.2 mg/kg of body weight; ip) daily for 14 days before a 10 min common carotid artery occlusion (CCAO). After CCAO, we administrated sodium selenite (6 µg/kg of body weight; ip) daily for 7 days. In the temporoparietal cerebral cortex, we determined nitrites by the Griess method and lipid peroxidation by the Gerard-Monnier assay. qPCR was used to measure mRNA of nitric oxide synthases, antioxidant enzymes, chemokines, and their receptors. We measured the enzymatic activity of SOD and GPx and protein levels of chemokines and their receptors by ELISA. We evaluated long-term memory using the Morris-Water maze test. Our results showed that prophylactic administration of zinc caused a preconditioning effect, decreasing nitrosative/oxidative stress and increasing GPx and SOD expression and activity, as well as eNOS expression. The therapeutic administration of selenium maintained this preconditioning effect up to the late phase of hypoxia-ischemia. Ccl2, Ccr2, Cxcl12, and Cxcr4 were upregulated, and long-term memory was improved. Pyknotic cells were decreased suggesting prevention of neuronal cell death. Our results show that the prophylactic zinc and therapeutic selenium administration induces effective neuroprotection in the early and late phases after CCAO.
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Antioxidantes/metabolismo , Córtex Cerebral/efeitos dos fármacos , Hipóxia-Isquemia Encefálica/metabolismo , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Selenito de Sódio/administração & dosagem , Zinco/administração & dosagem , Animais , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
BACKGROUND: Cytokines play important roles in the physiopathology of dengue infection; therefore, the suppressors of cytokine signaling (socs) that control the type and timing of cytokine functions could be involved in the origin of immune alterations in dengue. OBJECTIVE: To explore the association of cytokine and socs levels with disease severity in dengue patients. METHODS: Blood samples of 48 patients with confirmed dengue infection were analyzed. Amounts of interleukins IL-2, IL-4, IL-6, and IL-10, interferon- (IFN-) γ, and tumor necrosis factor- (TNF-) α were quantified by flow cytometry, and the relative expression of socs1 and socs3 mRNA was quantified by real-time RT-PCR. RESULTS: Increased levels of IL-10 and socs3 and lower expression of socs1 were found in patients with dengue hemorrhagic fever (DHF) with respect to those with dengue fever (DF) (p < 0.05). Negative correlations were found between socs1 and both IL-10 and socs3 (p < 0.01). The cutoff values of socs3 (>199.8-fold), socs1 (<1.94-fold), and IL-10 (>134 pg/ml) have the highest sensitivity and specificity to discriminate between DF and DHF. CONCLUSION: Simultaneous changes in IL-10 and socs1/socs3 could be used as prognostic biomarkers of dengue severity.
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Interleucina-10/metabolismo , Dengue Grave/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Animais , Biomarcadores/metabolismo , Feminino , Citometria de Fluxo , Humanos , Interferon gama/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Masculino , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The molecular structure modeling of the ß1 subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4) was carried out in the twilight zone of very low homology. Structural significance can per se be confounded with random sequence similarities. Hence, we combined (i) not automated computational modeling of weakly homologous 3D templates, some with interfaces to analogous structures to the pore-bearing Nav1.4 α subunit with (ii) site-directed mutagenesis (SDM), as well as (iii) electrophysiological experiments to study the structure and function of the ß1 subunit. Despite the distant phylogenic relationships, we found a 3D-template to identify two adjacent amino acids leading to the long-awaited loss of function (inactivation) of Nav1.4 channels. This mutant type (T109A, N110A, herein called TANA) was expressed and tested on cells of hamster ovary (CHO). The present electrophysiological results showed that the double alanine substitution TANA disrupted channel inactivation as if the ß1 subunit would not be in complex with the α subunit. Exhaustive and unbiased sampling of "all ß proteins" (Ig-like, Ig) resulted in a plethora of 3D templates which were compared to the target secondary structure prediction. The location of TANA was made possible thanks to another "all ß protein" structure in complex with an irreversible bound protein as well as a reversible protein-protein interface (our "Rosetta Stone" effect). This finding coincides with our electrophysiological data (disrupted ß1-like voltage dependence) and it is safe to utter that the Nav1.4 α/ß1 interface is likely to be of reversible nature.
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INTRODUCCIÓN. La radioterapia de intensidad modulada (IMRT) constituye una técnica de alta precisión basada en la definición volumétrica tridimensional de la anatomía del tumor y de los órganos críticos o en riesgo. Con el objetivo de asegurar la posibilidad de aplicar la IMRT en Cuba, en casos seleccionados de tumores en niños y adolescentes, se instrumentó un proyecto de investigación cuyos resultados se documentan en este informe. MÉTODOS. Se realizaron las primeras irradiaciones con IMRT en niños y adolescentes cubanos, con edades entre 6 y 18 años. La técnica empleada es la basada en aperturas geométricas y optimización inversa. Las irradiaciones fueron realizadas con un acelerador lineal con fotones de 6 MV, con colimador multiláminas. Las dosis de radiaciones administradas variaron según el tipo de tumor, y de acuerdo con las normas de radioterapia y la presencia de órganos críticos. Todos los pacientes fueron evaluados semanalmente, con controles radiológicos mediante placas portales electrónicas. RESULTADOS. Los pacientes irradiados (5) tenían los tumores siguientes: linfoma no-Hodgking del seno maxilar (1), glioma del tallo cerebral (1), linfoma no-Hodgking abdominal (1), condrosarcoma mesenquimatoso parameníngeo (1) y hemangiopericitoma parameníngeo (1). Las dosis de irradiación recibidas variaron entre 24 y 62 Gy. Fueron empleados entre 5 y 8 campos, con variaciones entre 10 y 20 segmentos. CONCLUSIONES. Se realizaron en Cuba las primeras irradiaciones con IMRT en niños y adolescentes, y se debe continuar extendiendo su empleo en aquellos casos donde su utilidad sea mayor
INTRODUCTION. The intensity modulated radiotherapy (IMRT) is a high performance technique based on the three-dimensional volumetric definition of tumor anatomy and of critical organs or at risk. To assure the possibility to apply the IMRT in Cuba in selected cases of tumors in children and adolescents, authors designed a research project whose results are documented in present report. METHODS. The first irradiations with IMRT in Cuban children and adolescents aged between 6 -18 were carried out. The technique used is that based on the geometric openings and inverse optimization. Irradiations were applied using a linear accelerator with 6 MV photons, with multileaf collimator. Doses administered varied according to the type of tumor, the radiotherapy standards and the presence of critical organs. All patients were assessed weekly with radiologic controls using electronic portal plates. RESULTS. Irradiated patients (5) had the following tumors: non-Hodgkin lymphoma of maxillary sinus (1), brain stem glioma (1), non-Hodgkin abdominal lymphoma (1), parameningeal mesenchymatous chondrosarcoma (1) and parameningeal hemangiopericytoma (1). Doses of radiation applied varied between 24 and 62 Gy. Between 5 and 8 fields were used with variations among 10 and 20 segments. CONCLUSIONS. In Cuba the first irradiations with IMRT in children and adolescents and its use must to be spreading to those cases where its usefulness is greater
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INTRODUCCIÓN. El angiofibroma juvenil de nasofaringe es un tumor benigno infrecuente, compuesto de tejido conectivo fibroso y abundancia de espacios vasculares revestidos de endotelio. Es casi exclusivo del sexo masculino y de la adolescencia. El tratamiento de elección es la exéresis, sin descartar otras posibilidades como la radioterapia. El objetivo del presente estudio fue presentar los resultados de esta última como opción terapéutica. MÉTODOS. Se estudió una serie de 11 pacientes, todos del sexo masculino, con edades entre 9 y 16 años, que fueron tratados en el Instituto Nacional de Oncología y Radiobiología de La Habana entre 1990 y 2005. Los pacientes fueron seguidos entre 48 y 306 meses. La radioterapia aplicada consistió en la irradiación de todo el volumen tumoral, con un margen de seguridad, en dosis de 40 a 60 Gy, con 1,8 Gy por sesión. Asociado a la radioterapia se utilizó interferón, durante y después de la irradiación, y poliquimioterapia en 1 paciente. RESULTADOS. Se obtuvo la remisión completa mantenida, sin recidivas, en 10 pacientes. No hubo pacientes con un segundo tumor. Presentaron complicaciones tempranas todos los pacientes, y tardías, solo algunos. Entre las complicaciones tempranas se halló radiomucositis y conjuntivis radiógena, y las más graves de las tardías fueron la pérdida permanente de las pestañas del párpado inferior en un caso y cataratas radiógenas en 4 pacientes. CONCLUSIONES. La radioterapia es un tratamiento que conserva su utilidad e indicaciones específicas.
INTRODUCTION: The nasopharyngeal juvenile angiofribroma is a uncommon benign tumor composed of fibrous connective tissue and many vascular spaces covered by endothelium. It is almost exclusive of male sex and of adolescents. Choice treatment is the exeresis without obviate other possibilities as the radiotherapy. The aim of present study was to show the results of this latter as therapeutical option. METHODS: Authors studied a series of 11 male patients, aged between 9 and 16, seen in National Institute of Oncology and Radiobiology of La Habana between1990 and 2005. Patients were followed during 48 and 306 months. Radiotherapy applied was the irradiation of all the tumor volume with a accuracy margin in dose of 40 and 60 Gy, with 1,8 Gy by session. Together with radiotherapy we used Interferon, during and after irradiation and polychemotherapy in one patient. RESULTS: There was a maintained complete remission without relapses in 10 patients. There weren't patients with a second tumor. All patients had early complications and late in some of them. Among the early complications we found radiomucositis and radiogenic conjunctivitis and the more severe of the late complications were the permanent loss of eyelash of lower eyelid in a case and radiogenic cataract in 4 patients. CONCLUSIONS: Radiotherapy is a treatment maintaining its usefulness and specific indications.
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INTRODUCCIÓN. La proctosigmoidectomía con resección mesorrectal total, reservorio en J y anastomosis coloanal es útil en los pacientes con cánceres de recto medio y bajo, para evitar la colostomía terminal definitiva. El objetivo de este trabajo fue analizar la factibilidad de dicha técnica quirúrgica, el tratamiento integral multidisciplinario y los resultados obtenidos. MÉTODOS. Se estudiaron 15 pacientes que padecían adenocarcinomas de recto medio y bajo, tratados entre enero de 1996 y diciembre de 2002 en el servicio de Cirugía Esplácnica del Instituto Nacional de Oncología y Radiobiología de La Habana. El tratamiento consistió en una combinación de radioterapia más quimioterapia concurrentes neoadyuvantes, seguidas de cirugía y quimioterapia adyuvante. RESULTADOS. La edad promedio de los pacientes fue de 56 años. El adenocarcinoma fue el tipo histológico diagnosticado en todos los pacientes. La estadificación de los tumores fue la siguiente: T1 y T2, 4 pacientes (27 por ciento, respectivamente); T3, 7 pacientes (46 por ciento). Cuatro pacientes (20 por ciento) se complicaron como consecuencia del tratamiento radiante y 5 (33,3 por ciento), a causa del tratamiento quirúrgico. La mortalidad quirúrgica fue de 1 paciente (6,6 por ciento) y 11 pacientes (73,3 por ciento) sobrevivieron más de 5 años. Ningún paciente presentó recidiva tumoral pélvica ni de la anastomosis coloanal. Se logró buena continencia esfinteriana. CONCLUSIONES. La resección mesorrectal total y anastomosis coloanal con reservorio colónico en J evita la colostomía terminal definitiva, cura a un alto porcentaje de pacientes con cánceres de recto medio y bajo, no transgrede los principios de la cirugía oncológica, es bien aceptada por los pacientes y es factible en nuestro medio(AU)
INTRODUCTION: Proctosigmoidectomy with total mesorectum resection, reservoir in J and colorectal is useful in patients with low and middle rectum cancer, to avoid the definite terminal colostomy. The aim of present paper was to analyze the feasibility of such surgical technique, the multidisciplinary integral treatment and the results obtained. METHODS: Fifteen patients were studied suffering of low and middle adenocarcinoma treated between January, 1996 and December, 2002 in Splanchnic Surgery Service of National Institute of Oncology and Radiobiology of La Habana City. Treatment included a combination of radiotherapy plus neocoadjuvant concurrent chemotherapy, followed by adjuvant chemotherapy and surgery. RESULTS: Mean age of patients was of 56 years. The adenocarcinoma was the histological type diagnosed in all patients. Tumor staging the following: T1 and T2, in four patients (27 percent, respectively); T3 in seven patients (46 percent). Four patients (20 percent) had complications due to radiation treatment and five (33,3 percent), by surgical treatment. Surgical mortality occurred in one patient (6,6 percent) and eleven patients (73,3 percent) survived over 5 years. Neither patient had pelvic tumor relapse or by colorectal anastomosis. There was good sphincter continence. CONCLUSIONS: Total mesorectum resection and colorectal anastomosis with a colonic reservoir in J prevent the definite terminal colostomy, to cure a high percentage of patients with low and middle rectum cancer without respecting the oncology surgery principles, is well accepted by patients and it is feasible in our practice(AU)
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Humanos , Protectomia/métodos , Neoplasias Retais/cirurgia , Proctocolectomia Restauradora/métodos , Anastomose Cirúrgica/métodos , Quimioterapia Adjuvante/métodosRESUMO
Urabe AM9 mumps virus vaccine causes post-vaccination meningitis. Two variants of Urabe AM9 virus differ in their replication efficiency in human nerve cells, HN-A(1081) variant being more neurotropic than HN-G(1081). The effect of interferon (IFN) on viral replication and transcription was analyzed. Priming of nerve cells with IFN reduced more significantly the replication of HN-G(1081) variant (from 10(2.5) to 10(1.3) TCID(50)) than that of HN-A(1081) (from 10(3.5) to 10(2.6) TCID(50)). IFN-priming also reduced the transcription of HN-G(1081) genes, but not of HN-A(1081). The effect of viral infection on the transcription of cellular IFN responsive genes was analyzed. HN-A(1081) virus reduced the transcription of STAT1, STAT2, p48 and MxA in both unprimed and IFN-primed cells; whereas HN-G(1081) virus just reduced MxA transcription. Since rubulavirus V protein inhibits IFN signaling, the V mRNA was cloned and sequenced, finding that HN-G(1081) but not HN-A(1081) presented three extra G in the P/V edition site, producing the insertion of Gly156 in the V protein. Our results suggest that the replication efficiency of Urabe AM9 mumps virus variants is influenced by their sensitivity to interferon and their capacity to reduce the antiviral response.