Abstract Lung cancer is the leading cause of cancer-related death, and NSCLC constitutes nearly 85%–90% of all cases. The IRS proteins function as adaptors and transmit signals from multiple receptors. Upon binding of insulin to the insulin receptor (IR), IRS1 is phosphorylated at several YXXM motifs creating docking sites for the binding of PI3Kp85, which activates AKT kinase. Therefore, we thought that gain of function mutantions of IRS1 could be related to development of lung cancer. In line with this, we wanted determine whether the IRS1 gene was mutated in the coding regions surrounding YXXM motifs. We sequenced the coding regions surrounding YXXM motifs of IRS1 using tumor samples of 42 NSCLC patients and 40 matching controls and found heterozygote p.S668T mutation in nine of 42 samples and four of nine also had the p.D674H mutation. We generated IRS1 expression vectors harboring p.S668T, p.D674H and double mutants. Expression of the mutants differentially affected insulin-induced phosphorylation of IRS1, AKT, ERK, and STAT3. Also, our mutants induced proliferation, glucose uptake, inhibited the migration of 293T cells and affected the responsiveness of the cells to cisplatin and radiation. Our results suggest that these novel mutations play a role in the phenotype of lung cancer.

Abstract Introduction: 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency is an autosomal recessive disorder that usually presents in the neonatal period with vomiting, metabolic acidosis, hypoglycemia and absent ketonuria. Few cases are reported in the literature, and optimal dietary management and long term outcome are not fully understood. Case report: We report a 2 year old girl with HMG-CoA-lyase deficiency who had limited fasting tolerance on a low protein diet, with several recurrent hospital admissions with severe hypoketotic hypoglycaemia and metabolic acidosis. We also review the dietary management and outcome of other reported cases in the literature. Discussion: In order to define optimal dietary treatment, it is important to collect higher numbers of case studies with detailed dietary management, fasting times and outcome.

Resumen Introducción: la deficiencia de la 3-hidroxi-3-metilglutaril-CoA (HMG-CoA) liasa es un desorden autosómico recesivo que normalmente se presenta en la infancia con vómitos, acidosis metabólica, hipoglicemia y sin cetonuria. Se han publicado pocos casos en la literatura científica sobre el mejor tratamiento dietético para el adecuado desarrollo de los pacientes a largo plazo, por lo que esta deficiencia no es bien conocida. Caso clínico: presentamos una niña de 2 años con deficiencia de la 3-hidroxi-3-metilglutaril-CoA (HMG-CoA) liasa. Recibiendo una dieta baja en proteína con una tolerancia de ayuno limitada con episodios recurrentes de admisión hospitalaria con hipoglicemia hipoketótica y acidosis metabólica. También hemos revisado el tratamiento dietético y el desarrollo de otros casos publicados en la literatura científica. Discusión: es importante recoger más casos clínicos describiendo el tratamiento dietético seguido, el tiempo máximo de ayuno y el desarrollo de los pacientes con el objetivo de definir el mejor tratamiento.

RESUMO Objetivo: Determinar o impacto da síndrome pós-pólio na qualidade de vida nos sobreviventes da pólio. Métodos: Quarenta sobreviventes da pólio foram incluídos no estudo. Participaram do grupo de síndrome pós-pólio 21 pacientes que atenderam aos critérios de síndrome pós-pólio de Halstead. Os 19 restantes formaram o grupo não síndrome pós-pólio. O grupo controle foi composto por 40 indivíduos saudáveis. A qualidade de vida foi avaliada pelo Nottingham Health Profile, a depressão pela Escala de Depressão de Beck e a fadiga pelo Inventário de Sintomas de Fadiga. A força muscular isométrica foi medida por teste muscular manual. Resultados: O escore total do teste muscular manual foi 26,19 ± 13,24 (mediana: 29) no grupo de síndrome pós-pólio e 30,08 ± 8,9 (mediana: 32) no grupo não síndrome pós-pólio. Escores totais de teste muscular manual de grupo não síndrome pós-pólio foram significativamente maiores do que os do grupo de síndrome pós-pólio. Os pacientes com síndrome pós-pólio relataram níveis significativamente maiores de fadiga e qualidade de vida reduzida em termos de mobilidade física, dor e energia quando comparados com pacientes sem síndrome pós-pólio e grupo controle. Não se relatou uma diferença estatisticamente significativa no funcionamento social e emocional e na qualidade do sono entre grupos de síndrome pós-pólio, não síndrome pós-pólio e controle. Além disso, não se encontrou diferença estatisticamente significativa nos escores da Escala de Depressão de Beck entre os grupos. Conclusões: A síndrome pós-pólio tem um impacto negativo na qualidade de vida em termos de estado funcional, gravidade da dor e energia. A identificação, o reconhecimento precoce e a reabilitação dos pacientes com síndrome pós-pólio podem resultar em uma melhoria da qualidade de vida.

ABSTRACT Objective: To determine the impact of postpolio-syndrome on quality of life in polio survivors. Methods: Forty polio survivors were included in the study. Twenty-one patients fulfilling the Halstead's postpolio-syndrome criteria participated in postpolio-syndrome group. The remaining nineteen patients formed non-postpolio-syndrome group. Control group was composed of forty healthy subjects. Quality of life was evaluated by Nottingham Health Profile, depression by Beck Depression Scale and fatigue by Fatigue Symptom Inventory. Isometric muscle strength was measured by manual muscle testing. Results: Total manual muscle testing score was 26.19 ± 13.24 (median: 29) in postpolio-syndrome group and 30.08 ± 8.9 (median: 32) in non-postpolio-syndrome group. Total manual muscle testing scores of non-postpolio-syndrome group were significantly higher than that of postpolio-syndrome group. Patients with postpolio-syndrome reported significantly higher levels of fatigue and reduced quality of life in terms of physical mobility, pain and energy when compared with patients without postpolio-syndrome and control group. It was not reported a statistically significant difference in social and emotional functioning and sleep quality between postpolio-syndrome, non-postpolio-syndrome and control groups. Also it was not found any statistically significant difference in Beck Depression Scale scores among the groups. Conclusions: Postpolio-syndrome has a negative impact on quality of life in terms of functional status, severity of pain and energy. The identification, early recognition and rehabilitation of postpolio-syndrome patients may result in an improvement in their quality of life.