Recommendations from Experts in the Management of Adverse Reactions to ALK Inhibitors (2021 Version) / 中国肺癌杂志

Anaplastic lymphoma kinase (ALK) fusion gene, as a tumor driver gene, was crucial for the occurrence and development of non-small cell lung cancer (NSCLC). Recently, targeted ALK fusion gene has become the main treatment method for ALK-positive NSCLC. The first and second generation ALK inhibitors (ALKi), such as crizotinib, ceritinib, alectinib and ensartinib have been approved in China. However, there was no guidance for the management of ALKi adverse reactions. Therefore, this "Recommendations from experts in the management of adverse reactions to ALK inhibitors (2021 version)" has been summarized, led by Lung Cancer Professional Committee of Sichuan Cancer Society and Sichuan Medical Quality Control Center for Tumor Diseases, to provide practical and feasible strategies for clinical ALKi management specification of adverse reactions.
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Children's eating behavior: comparison between normal and overweight children from a school in Pelotas, Rio Grande do Sul, Brazil / Comportamento alimentar infantil: comparação entre crianças sem e com excesso de peso em uma escola do município de Pelotas, RS

OBJECTIVE: To evaluate differences in children's eating behavior in relation to their nutritional status, gender and age. METHODS: Male and female children aged six to ten years were included. They were recruited from a private school in the city of Pelotas, Rio Grande do Sul, southern Brazil, in 2012. Children´s Eating Behaviour Questionnaire (CEBQ) subscales were used to assess eating behaviors: Food Responsiveness (FR), Enjoyment of Food (EF), Desire to Drink (DD), Emotional Overeating (EOE), Emotional Undereating (EUE), Satiety Responsiveness (SR), Food Fussiness (FF) and Slowness in Eating (SE). Age-adjusted body mass index (BMI) z-scores were calculated according to the WHO recommendations to assess nutritional status. RESULTS: The study sample comprised 335 children aged 87.9±10.4 months and 49.3% had normal weight (n=163), 26% were overweight (n=86), 15% were obese (n=50) and 9.7% were severely obese (n=32). Children with excess weight showed higher scores at the CEBQ subscales associated with "food approach" (FR, EF, DD, EOE, p<0.001) and lower scores on two "food avoidance" subscales (SR and SE, p<0.001 and p=0.003, respectively) compared to normal weight children. Differences in the eating behavior related to gender and age were not found. CONCLUSIONS: "Food approach" subscales were positively associated to excess weight in children, but no associations with gender and age were found. .

OBJETIVO: Avaliar diferenças no comportamento alimentar infantil em função do estado nutricional, do sexo e da idade. MÉTODOS: O estudo incluiu crianças na faixa de seis a dez anos, de ambos os sexos, de uma escola privada em Pelotas (RS), em 2012. Para avaliar o comportamento alimentar usaram-se as subescalas do questionário Children's Eating Behaviour Questionnaire (CEBQ): resposta à comida (FR), prazer de comer (EF), desejo de beber (DD), sobreingestão emocional (EOE), subingestão emocional (EUE), resposta à saciedade (SR), seletividade (FF) e ingestão lenta (SE). Avaliou-se o estado nutricional por meio do escore-z do IMC/idade. RESULTADOS: Participaram 335 crianças de 87,9±10,4 meses. Apresentaram eutrofia 49,3% (n=163), sobrepeso 26% (n=86), obesidade 15% (n=50) e obesidade grave 9,7% (n=32). Crianças com excesso de peso tiveram maior pontuação nas subescalas de "interesse pela comida" (FR, EF, DD, EOE, p<0,001) e menor pontuação nas subescalas de "desinteresse pela comida" (SR e SE, p<0,001 e p=0,003, respectivamente), se comparadas com as crianças com peso adequado. Não foram observadas diferenças no comportamento alimentar segundo sexo e idade. CONCLUSÕES: Observou-se que comportamentos alimentares que refletem "interesse pela comida" estão associados positivamente ao excesso de peso, mas não foi encontrada associação com o sexo e a idade da criança. .

Mecanismes moleculaires de la leucemie myeloide chronique

Chronic myeloid leukaemia is a hronic disorder of the pluripotent hematopoietic stem cell chracterised by reciprocal chromosomal translocation, Ph chromosome. Molecular haematology development is one stage of the progress in diagnostic and therapeutic care of malignant hemopatology. In this review, wwe report the molecular mechanisms of chronic myelogenous leukaemia that include chimerics gens and protein. The deregulated tyrosine kinase activity gives excessive proliferation. Inhibition of the expression of the tyrosine kinase by Imatinib [STI571, GLIVEC] is therapeutic manoeuver

Inhibition of vascular endothelial growth factor (VEGF) as a novel approach for cancer therapy

Of the numerous growth factors and cytokines that have been shown to have angiogenic effects, vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), appears to be a key factor in pathological situations which involve neovascularization as well as enhanced vascular permeability. Our aim was to design a low molecular weight synthetic molecule that potently and selectively blocks the VEGF/VEGF receptor system after oral administration, suitable for the chronic therapy of VEGF-dependent pathological neovascularization. PTK787/ZK 222584 is a potent inhibitor of VEGF receptor tyrosine kinases, active in the submicromolar range. It also inhibits other class III kinases, like the PDGFR-beta tyrosine kinase, c-Kit and c-Fms, but at higher concentrations. It is not active against kinases from other receptor families such as EGFR, FGFR-1, c-Met and Tie-2 or intracellular kinases like c-Src, c-Abl, PKC-alpha. PTK787/ZK 222584 inhibits VEGF-induced autophosphorylation of KDR, and endothelial cell proliferation, migration and survival in the nanomolar range in cell based assays. In concentrations up to 1 microM, PTK787/ZK 222584 does not have any cytotoxic or anti-proliferative effect on cells that do not express VEGF receptors. After oral dosing (50 mg/kg) to mice, plasma concentrations of PTK787/ZK 222584 remain above 1 microM for more than 8 h. PTK787/ZK 222584 induces dose-dependent inhibition of VEGF- and PDGF-induced angiogenesis in a growth factor implant model, as well as a tumor cell-driven angiogenesis model after once daily oral dosing (25-100 mg/kg). In the same dose range, it also inhibits the growth of several human carcinomas, grown subcutaneously in nude mice, as well as a murine renal carcinoma and its metastases in syngeneic, orthotopic models. Histological examination of tumors reveals inhibition of microvessel formation in the interior of the tumor. PTK787/ZK 222584 also significantly inhibits ascites formation induced by a human ovarian carcinoma grown in the peritoneum of nude mice as well as pleural effusion induced by a human lung adenocarcinoma in nude mice. PTK787/ZK 222584 is very well tolerated and does not impair wound healing. It also does not have any significant effects on circulating blood cells or bone marrow leukocytes as a single agent, or impair hematopoetic recovery following concomitant cytotoxic anti-cancer agent challenge. These studies indicate that compounds that inhibit the effects of VEGF, such as PTK787/ZK 222584, have the potential to provide a novel, effective and well-tolerated therapy for the treatment of solid tumors. These agents may also provide a new therapeutic approach for the treatment of other diseases where angiogenesis plays an important role.