Guidance on the management of adverse reactions induced by poly(ADP-ribose) polymerase inhibitors / 浙江大学学报·医学版

The common adverse reactions caused by poly (ADP-ribose) polymerase (PARP) inhibitors include hematological toxicity, gastrointestinal toxicity and fatigue. The main prevention and treatment of hematological toxicity include: regular blood tests, referral to hematology department when routine treatment is ineffective, and being alert of myelodysplastic syndrome/acute myeloid leukemia. The key points to deal with gastrointestinal toxicity include: taking medicine at the right time, light diet, appropriate amount of drinking water, timely symptomatic treatment, prevention of expected nausea and vomiting, and so on. For fatigue, full assessment should be completed before treatment because the causes of fatigue are various; the management includes massage therapy, psychosocial interventions and drugs such as methylphenidate and Panax quinquefolius according to the severity. In addition, niraparib and fluzoparib can cause hypertension, hypertensive crisis and palpitation. Blood pressure and heart rate monitoring, timely symptomatic treatment, and multidisciplinary consultation should be taken if necessary. When cough and dyspnea occur, high resolution CT and bronchoscopy should be performed to exclude pneumonia. If necessary, PARP inhibitors should be stopped, and glucocorticoid and antimicrobial therapy should be given. Finally, more attention should be paid to drug interaction management, patient self-management and regular monitoring to minimize the risk and harm of adverse reactions of PARP inhibitors.

Neuropsychomotor developmental delay: conceptual map, term definitions, uses and limitations / Atraso do desenvolvimento neuropsicomotor: mapa conceitual, definições, usos e limitações do termo

OBJECTIVE: To retrieve the origin of the term neuropsychomotor developmental delay" (NPMD), its conceptual evolution over time, and to build a conceptual map based on literature review. DATA SOURCE: A literature search was performed in the SciELO Brazil, Web of Science, Science Direct, OneFile (GALE), Pubmed (Medline), Whiley Online, and Springer databases, from January of 1940 to January of 2013, using the following keywords: NPMD delay, NPMD retardation, developmental delay, and global developmental delay. A total of 71 articles were selected, which were used to build the conceptual map of the term. DATA SYNTHESIS: Of the 71 references, 55 were international and 16 national. The terms developmental delay and global developmental delay were the most frequently used in the international literature and, in Brazil, delayed NPMD was the most often used. The term developmental delay emerged in the mid 1940s, gaining momentum in the 1990s. In Brazil, the term delayed NPMD started to be used in the 1980s, and has been frequently cited and published in the literature. Delayed development was a characteristic of 13 morbidities described in 23 references. Regarding the type of use, 19 references were found, with seven forms of use. Among the references, 34 had definitions of the term, and 16 different concepts were identified. CONCLUSIONS: Developmental delay is addressed in the international and national literature under different names, various applications, and heterogeneous concepts. Internationally, ways to improve communication between professionals have been indicated, with standardized definition of the term and use in very specific situations up to the fifth year of life, which was not found in Brazilian publications. .

OBJETIVO: Resgatar a origem do termo atraso do desenvolvimento neuropsicomotor (DNPM), sua evolução conceitual ao longo do tempo e construir mapa conceitual do termo com base em busca bibliográfica. FONTES DE DADOS: Foi realizada busca nas bases de dados eletrônicas do Portal da Capes, que incluem Scielo Brazil, Web of Science, Science Direct, OneFile (GALE), Pubmed (Medline), Whiley Online e Springer, referente a Janeiro/1940-Janeiro/2013. Palavras-chave: atraso e retardo do DNPM, developmental delay e global developmental delay. Foram selecionados 71 artigos e construído o mapa conceitual do termo. SÍNTESE DE DADOS: Das 71 referências, 55 eram internacionais e 16 nacionais. Os termos mais encontrados foram global developmental delay e developmental delay na literatura internacional e retardo e atraso do DNPM no Brasil. Internacionalmente, o termo surgiu em meados da década de 40 ganhando força nos anos 90. No Brasil, o termo começou a ser usado na década de 80 e vem sendo frequentemente citado na literatura. O atraso é citado em 23 trabalhos como característica presente em 13 tipos de condições clínicas. Com relação ao uso, foram encontrados 19 estudos, com sete situações de uso. Dentre os artigos revisados, 34 deles apresentaram definições, sendo identificados 16 conceitos diferentes. CONCLUSÕES: O atraso do desenvolvimento é abordado na literatura internacional e nacional sob diversos nomes, diferentes aplicações e conceitos heterogêneos. Internacionalmente, apontam-se caminhos para melhorar a comunicação entre profissionais, com definição padronizada do termo e uso em situações específicas até o quinto ano de vida, o que não foi encontrado nas publicações nacionais. .

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.