Efectividad del Heberferon en el tratamiento del carcinoma basocelular

El Carcinoma basocelular es el cáncer de piel más frecuente en el ser humano, representa aproximadamente entre un 70 y un 80 % de los cánceres cutáneos no melanoma en la población de color de piel blanca, este es un tumor maligno de estirpe epitelial y es el más frecuente en la consulta dermatológica, soliendo afectar a individuos mayores de 50 años con máxima incidencia entre la sexta y octava década de la vida. Se realizó un estudio postcomercialización, observacional, de serie de casos, de vigilancia temprana del medicamento en condiciones de práctica médica habitual. La investigación se ejecutó con los pacientes con diagnóstico de carcinoma basocelular, atendidos en la consulta en la consulta de oncodermatología, que tiene su sede Hospital ‟Carlos Manuel de Céspedes" de Bayamo, durante el período comprendido entre enero 2018 a diciembre 2019.El universo estuvo constituido por 120 pacientes y la muestra por 92 pacientes mayores de 18 años, a los que se les administró HeberFERON, resultando ser efectivo en el tratamiento de carcinoma basocelular de cualquier localización, tipo y tamaño. Se confirmó la efectividad en condiciones de práctica médica habitual, en las variables: respuesta clínica al tratamiento, utilizando para ello, los criterios RECIST, además mostró un perfil de seguridad adecuado. Los eventos adversos reportados fueron en su mayoría grado 1 y grado 2, según la clasificación del CTCAE, versión 5 y por su gravedad, se clasificaron no grave.

Basal cell carcinoma is the most frequent skin cancer in humans, representing approximately between 70 and 80% of non-melanoma skin cancers in the white-skinned population, this is a malignant tumor of epithelial lineage and is the most frequent in dermatological consultation, usually affecting individuals over 50 years of age with maximum incidence between the sixth and eighth decade of life. A post-marketing study was conducted, observational, case series, of early surveillance of the drug under conditions of routine medical practice. The research was carried out with patients diagnosed with basal cell carcinoma, attended in the consultation in the oncodermatology consultation, which has its headquarters Hospital ‟Carlos Manuel de Céspedes" of Bayamo, during the period from January 2018 to December 2019. The universe consisted of 120 patients and the sample was 92 patients over 18 years of age, who were administered HeberFERON, proving to be effective in the treatment of basal cell carcinoma of any location, type and size. The effectiveness in conditions of usual medical practice was confirmed, in the variables: clinical response to treatment, using the RECIST criteria, in addition to showing an adequate safety profile. The adverse events reported were mostly grade 1 and grade 2, according to the classification of the CTCAE, version 5 and due to their severity, they were classified as non-serious.

O carcinoma basocelular é o câncer de pele mais frequente em humanos, representando aproximadamente entre 70 e 80% dos cânceres de pele não melanoma na população de pele branca, sendo este um tumor maligno de linhagem epitelial e o mais frequente na consulta dermatológica, acometendo geralmente indivíduos com mais de 50 anos de idade com incidência máxima entre a sexta e a oitava década de vida. Foi realizado um estudo pós-comercialização, observacional, série de casos, de vigilância precoce da droga sobcondições de prática médica de rotina.A pesquisa foi realizada com pacientes diagnosticados com carcinoma basocelular, atendidos na consulta na consulta de oncodermatologia, que temsua sede no Hospital Carlos Manuel de Céspedes, de Bayamo, no período de janeiro de 2018 a dezembro de 2019. O universo foi composto por 120 pacientes e a amostra foi de 92 pacientes com mais de 18 anos de idade, aos quais foi administrado HeberFERON, mostrando-se eficaz no tratamento do carcinoma basocelular de qualquer localização, tipo e tamanho. A efetividade nas condições de prática médica habitual foi confirmada, nas variáveis: resposta clínica ao tratamento, utilizando-se os critérios RECIST, além de apresentarum perfil de segurança adequado. Os eventos adversos relatados foram, em sua maioria, grau 1 e grau 2, de acordo com a classificação do CTCAE, versão 5 e, devido à sua gravidade, foram classificados como não graves.

Clinical significance of intragraft miR-122 and -155 expression after liver transplantation.

AIM: Recurrent hepatitis C (RHC) and acute cellular rejection (AR) remain critical problems following liver transplantation (LT) in hepatitis C virus (HCV) positive recipients because of the similar clinical features. Discrimination between these conditions can be problematic, and adjunctive biomarkers would be useful to discriminate these processes. The aim of our study was to investigate the possibility of the intragraft miR-122 and -155 expression as new biomarkers after LT. METHODS: A total of 29 HCV positive recipients were enrolled in this study. Intragraft expressions of miR-122 and -155 were studied between RHC predominant (n = 17) and AR predominant cases (n = 12) using quantitative reverse transcription polymerase chain reaction. Furthermore, we investigated the correlations between these expression levels and clinical serum parameters. RESULTS: Intragraft miR-122 expression had a good correlation with serum alkaline phosphatase (P = 0.02), but it was not correlated with the serum HCV viral load. The expression levels of miR-122 in the AR group were significantly higher than those in the RHC group (P = 0.0006) and, inversely, the expression levels of miR-155 in the AR group were significantly lower than those in the RHC group (P = 0.01). CONCLUSION: Our study emphasizes a useful pattern of miR-122 and -155 as ancillary markers to discriminate AR predominant cases from RHC in HCV positive patients after LT.

Small molecule-mediated activation of the integrin CD11b/CD18 reduces inflammatory disease.

The integrin CD11b/CD18 (also known as Mac-1), which is a heterodimer of the α(M) (CD11b) and ß(2) (CD18) subunits, is critical for leukocyte adhesion and migration and for immune functions. Blocking integrin-mediated leukocyte adhesion, although beneficial in experimental models, has had limited success in treating inflammatory diseases in humans. Here, we used an alternative strategy of inhibiting leukocyte recruitment by activating CD11b/CD18 with small-molecule agonists, which we term leukadherins. These compounds increased the extent of CD11b/CD18-dependent cell adhesion of transfected cells and of primary human and mouse neutrophils, which resulted in decreased chemotaxis and transendothelial migration. Leukadherins also decreased leukocyte recruitment and reduced arterial narrowing after injury in rats. Moreover, compared to a known integrin antagonist, leukadherins better preserved kidney function in a mouse model of experimental nephritis. Leukadherins inhibited leukocyte recruitment by increasing leukocyte adhesion to the inflamed endothelium, which was reversed with a blocking antibody. Thus, we propose that pharmacological activation of CD11b/CD18 offers an alternative therapeutic approach for inflammatory diseases.

Endurance exercise is protective for mice with mitochondrial myopathy.

Defects in the mitochondrial ATP-generating system are one of the most commonly inherited neurological disorders, but they remain without treatment. We have recently shown that modulation of the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) level in skeletal muscle of a mitochondrial myopathy mouse model offers a therapeutic approach. Here we analyzed if endurance exercise, which is known to be associated with an increased PGC-1alpha level in muscle, offers the same beneficial effect. We subjected male and female mice that develop a severe mitochondrial myopathy due to a cytochrome-c oxidase deficiency at 3 mo of age to endurance exercise training and monitored phenotypical and metabolic changes. Sedentary myopathy and wild-type mice were used as controls. Exercise increased PGC-1alpha in muscle, resulting in increased mitochondrial biogenesis, and successfully stimulated residual respiratory capacity in muscle tissue. As a consequence, ATP levels were increased in exercised mice compared with sedentary myopathy animals, which resulted in a delayed onset of the myopathy and a prolonged lifespan of the exercised mice. As an added benefit, endurance exercise induced antioxidant enzymes. The overall protective effect of endurance exercise delayed the onset of the mitochondrial myopathy and increased life expectancy in the mouse model. Thus stimulating residual oxidative phosphorylation function in the affected muscle by inducing mitochondrial biogenesis through endurance exercise might offer a valuable therapeutic intervention for mitochondrial myopathy patients.

Mice lacking COX10 in skeletal muscle recapitulate the phenotype of progressive mitochondrial myopathies associated with cytochrome c oxidase deficiency.

We have created a mouse model with an isolated cytochrome c oxidase (COX) deficiency by disrupting the COX10 gene in skeletal muscle. Missense mutations in COX10 have been previously associated with mitochondrial disorders. Cox10p is a protoheme:heme-O-farnesyl transferase required for the synthesis of heme a, the prosthetic group of the catalytic center of COX. COX10 conditional knockout mice were generated by crossing a LoxP-tagged COX10 mouse with a transgenic mouse expressing cre recombinase under the myosin light chain 1f promoter. The COX10 knockout mice were healthy until approximately 3 months of age when they started developing a slowly progressive myopathy. Surprisingly, even though COX activity in COX10 KO muscles was <5% of control muscle at 2.5 months, these muscles were still able to contract at 80-100% of control maximal forces and showed only a 10% increase in fatigability, and no signs of oxidative damage or apoptosis were detected. However, the myopathy worsened with time, particularly in female animals. This COX10 KO mouse allowed us to correlate the muscle function with residual COX activity, an estimate that can help predict the progression pattern of human mitochondrial myopathies.

Cytochrome c association with the inner mitochondrial membrane is impaired in the CNS of G93A-SOD1 mice.

A "gain-of-function" toxic property of mutant Cu-Zn superoxide dismutase 1 (SOD1) is involved in the pathogenesis of some familial cases of amyotrophic lateral sclerosis (ALS). Expression of a mutant form of the human SOD1 gene in mice causes a degeneration of motor neurons, leading to progressive muscle weakness and hindlimb paralysis. Transgenic mice overexpressing a mutant human SOD1 gene (G93A-SOD1) were used to examine the mitochondrial involvement in familial ALS. We observed a decrease in mitochondrial respiration in brain and spinal cord of the G93A-SOD1 mice. This decrease was significant only at the last step of the respiratory chain (complex IV), and it was not observed in transgenic wild-type SOD1 and nontransgenic mice. Interestingly, this decrease was evident even at a very early age in mice, long before any clinical symptoms arose. The effect seemed to be CNS specific, because no decrease was observed in liver mitochondria. Differences in complex IV respiration between brain mitochondria of G93A-SOD1 and control mice were abolished when reduced cytochrome c was used as an electron donor, pinpointing the defect to cytochrome c. Submitochondrial studies showed that cytochrome c in the brain of G93A-SOD1 mice had a reduced association with the inner mitochondrial membrane (IMM). Brain mitochondrial lipids, including cardiolipin, had increased peroxidation in G93A-SOD1 mice. These results suggest a mechanism by which mutant SOD1 can disrupt the association of cytochrome c with the IMM, thereby priming an apoptotic program.

An ALS mouse model with a permeable blood-brain barrier benefits from systemic cyclosporine A treatment.

To test potentially beneficial drugs to amyotrophic lateral sclerosis (ALS), we created an ALS mouse model with a permeable blood-brain barrier, by crossing the G93A-SOD1 transgenic mouse with a multiple drug resistance type 1a/b (mdr1a/b) gene knockout mouse. To validate the model, we administered cyclosporine A intraperitoneally to the mice. Cyclosporine A accumulated in the brain and spinal cord of this mouse model, whereas it was unable to penetrate the CNS of mdr1a/b wild-type animals. Systemic administration of cyclosporine A extended the life of the double-mutant male mice by approximately 12%. Surprisingly, the effect was more robust in male mice and only marginal in female mice. These results demonstrate the usefulness of this combined mouse model for the testing of potentially therapeutic drugs and support the role of mitochondrial-mediated apoptosis in the pathway to motor neuron death in SOD1-associated ALS.

Regular exercise is beneficial to a mouse model of amyotrophic lateral sclerosis.

We tested whether a regular exercise regimen was associated with a change in the life span of G93A-SOD1 transgenic mice, a model of familial ALS. Regular treadmill running for 10 weeks led to a significant increase in the life span of G93A-SOD1 mice. The effect was stronger in male mice, whereas there was only a trend between exercised and sedentary female G93A-SOD1 mice. The data suggest that regular exercise has a beneficial effect on the progression of ALS.