Respuesta molecular profunda con ponatinib en leucemia mieloide crónica en fase crónica con resistencia a imatinib y dasatinib: Reporte de caso y revisión de la literatura / Profound molecular response with ponatinib in chronic phase of chronic myeloid leukemia with resistance to imatinib and dasatinib: Case report and review of the literature

RESUMEN Se reporta el caso de una mujer quien a la edad de 54 años fue diagnosticada de leucemia mieloide crónica en fase crónica; inició tratamiento con inhibidor de tirosina cinasa de primera generación, y evidenció falla por ausencia de respuesta hematológica y citogenética. A pesar del cambio de tratamiento a un inhibidor de tirosina cinasa de segunda generación (dasatinib), no fue posible alcanzar niveles óptimos de respuesta, documentándose la positividad para la mutación T315I en dominio ABL de la tirosina cinasa desregulada BCR/ABL, frente a la cual el único medicamento que muestra actividad es ponatinib. Luego de iniciar tratamiento con ponatinib, se evidenciaron niveles óptimos de respuesta citogenética y molecular, así como una adecuada calidad de vida de la paciente.

SUMMARY We report the case of a woman who at the age of 54 years was diagnosed with chronic myeloid leukemia in chronic phase; she began treatment with a first-generation tyrosine kinase inhibitor, and evidenced failure due to the absence of a hematological and cytogenetic response. Despite changing treatment to a second-generation tyrosine kinase inhibitor (dasatinib), it was not possible to achieve optimal levels of response, documenting positivity for the T315I mutation in the ABL domain of the deregulated BCR/ABL tyrosine kinase, compared to ponatinib, the only drug that shows activity. After starting treatment with ponatinib, optimal levels of cytogenetic and molecular response were evidenced, as well as an adequate quality of life for the patient.

Role of BDNF/TrkB signaling pathway in 17β estradiol-induced reduction of long-term cognitive impairment induced by multiple propofol anesthesia in developing rats / 中华麻醉学杂志

Objective:To evaluate the role of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway in 17β estradiol-induced reduction of long-term cognitive impairment induced by multiple propofol anesthesia in developing rats.Methods:Eighty 7-day-old clean-grade healthy newborn Sprague-Dawley rats of both sexes, weighing 11-17 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), propofol group (group P), 17β estradiol plus propofol group (EP group) and 17β estradiol plus propofol plus BDNF/TrkB signaling pathway blocker K252a group (K group). Propofol 80 mg/kg was intraperitoneally injected every day for 5 days in P, EP and K groups.The equal volume of fat emulsion was given instead in group C. In EP and K groups, 17β estradiol 600 μg/kg was subcutaneously injected at 30 min before propofol injection.BDNF/TrkB signaling pathway blocker K252a 100 μg/kg was intraperitoneally injected in group K. Morris water maze test was performed on days 30-34 after birth to assess the cognitive function.The rats were sacrificed after the end of Morris water maze test, and the hippocampal tissues were removed for determination of the apoptosis rate of hippocampal neurons (by flow cytometry), expression of BDNF, p-Trkb and cleaved caspase-3 (by Western blot and immunofluorescence), and expression of Bcl-2 and Bax mRNA (by real-time polymerase chain reaction) and for microscopic examination of the pathological changes in hippocampal CA1 region (with a light microscope). Bax mRNA/Bcl-2 mRNA ratio was calculated. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of BDNF and p-TrkB was down-regulated, the expression of cleaved caspase-3 was up-regulated, the apoptosis rate of hippocampal neurons and Bax mRNA/Bcl-2 mRNA ratio were increased ( P<0.05), and the pathological changes in hippocampal CA1 region were accentuated in group P. Compared with group P, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of BDNF and p-TrkB was up-regulated, the expression of cleaved caspase-3 was down-regulated, the apoptosis rate of hippocampal neurons and Bax mRNA/Bcl-2 mRNA ratio were decreased( P<0.05), and the pathological changes in hippocampal CA1 region were attenuated in group EP.Compared with group EP, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of BDNF and p-TrkB was down-regulated, the expression of cleaved caspase-3 was up-regulated, the apoptosis rate of hippocampal neurons and Bax mRNA/Bcl-2 mRNA ratio were increased( P<0.05), and the pathological changes in hippocampal CA1 region were accentuated in group K. Conclusions:BDNF/TrkB signaling pathway is involved in 17β estradiol-induced reduction of long-term cognitive impairment induced by multiple propofol anesthesia in developing rats.

The present research and progress of angiopoietin in diabetic retinopathy / 中华眼底病杂志

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, and it is the main cause of vision loss in diabetic patients. Angiopoietin (Ang), a superfamily of secreted proteins, is a vascular growth factor that regulates the stability of vascular environment, participates in angiogenesis and repair, and lipid metabolism. It plays an important role in the development of DR and has become a new target for the treatment of diabetic retinopathy. With the in-depth study of Ang and the research and development of various drugs for Ang, it is expected to bring new ideas and strategies for the treatment of DR in the future.

Role of BDNF/TrkB signaling pathway in pre-injection of young rat plasma-induced reduction of sevoflurane-caused cognitive dysfunction in aged rats / 中华麻醉学杂志

Objective:To evaluate the role of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling pathway in pre-injection of young rat plasma-induced reduction of sevoflurane-caused cognitive dysfunction in aged rats.Methods:Eighty SPF healthy male Sprague-Dawley rats, aged 18 months, weighing 550-650 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S), young rat plasma group (group Y) and BDNF/TrkB signaling pathway inhibitor K252a group (group K). The plasma 100 μl obtained from 3-month-old young rats was injected via the tail vein in group Y and group K, while the equal volume of normal saline was given via the tail vein in group C and group S, twice a week, for 4 weeks.In S, Y and K groups, 3% sevoflurane was inhaled for 3 h starting from the end of treatment, and BDNF/TrkB signaling pathway inhibitor K252a was injected via the tail vein before anesthesia in group K. The open field test and Morris water maze test were performed at 3 days after anesthesia to assess the spontaneous motor ability and cognitive function.Then the rats were sacrificed, and the hippocampal tissues were isolated for determination of the expression of BDNF, phosphorylated TrkB (p-TrkB), postsynaptic dense protein-95 (PSD-95) and synaptic vesicle protein (SYN) (by Western blot), dendritic length and dendritic ridge density of neurons in hippocampal CA1 area (by Golgi staining), and the number of synapses and length of synaptic active area (with a transmission electron microscope). Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-TrkB, BDNF, PSD-95 and SYN was down-regulated, and the dendritic length, dendritic ridge density, the number of synapses and length of synaptic active area were decreased in group S ( P<0.05). Compared with group S, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-TrkB, BDNF, PSD-95 and SYN was up-regulated, and the dendritic length, dendritic ridge density, the number of synapses and length of synaptic active area were increased in group Y ( P<0.05). Compared with group Y, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-TrkB, BDNF, PSD-95 and SYN was down-regulated, and the dendritic length, dendritic ridge density, the number of synapses and length of synaptic active area were decreased in group K ( P<0.05). Conclusions:The mechanism by which pre-injection of young rat plasma reduces sevoflurane-induced cognitive dysfunction is related to activation of BDNF/TrkB signaling pathway and improvement in synaptic plasticity in the hippocampus of aged rats.

Clinical research progress on radiopharmaceuticals imaging targeting epidermal growth factor receptor / 中华核医学与分子影像杂志

Epidermal growth factor receptor (EGFR) plays an important role in the development and occurrence of a variety of malignant tumors. Molecular targeted therapy for EGFR is in the ascendant. Molecular imaging can reveal the expression of EGFR and its mutations in vivo. The molecular probes labeled with 89Zr, 11C and 18F are used for imaging and the main research is about tyrosine kinase inhibitors labeled with 11C. PET is used to visualize EGFR expression and mutations in vivo, which can noninvasively screen patients suitable for targeting treatment and evaluate efficacy. This paper reviews the clinical researches and trials of these probes, and summarizes the clinical value of imaging methods, hoping to provide the evidence for clinical translation and application in the future.

Impacto econômico da interrupção do tratamento com inibidor de tirosina quinase em pacientes com leucemia mieloide crônica em um hospital federal referência em oncologia / Economic impact of discontinuing treatment with tyrosine kinase inhibitor in patients with chronic myeloid leukemia at a federal hospital reference in oncology

Objetivo: Avaliar o impacto econômico da descontinuação do tratamento da leucemia mieloide crônica (LMC) com inibidores da tirosina quinase (ITQs) em primeira ou segunda linha. Métodos: O modelo incluiu pacientes com diagnóstico de LMC em tratamento com ITQs que iniciaram o tratamento até 2012, em condições elegíveis no ano de 2015. Foi considerado um horizonte temporal de cinco anos sob a perspectiva do sistema público de saúde. Custos associados ao tratamento, como medicamento, monitoramento e manejo de eventos adversos, foram analisados. A avaliação foi composta por dois cenários: o cenário referência, com uso contínuo do medicamento, e o cenário comparador, com a interrupção do tratamento medicamentoso. Ambos os cenários consideraram as tecnologias disponíveis no período de 2015 a 2019. A análise de sensibilidade propôs variações nos cenários com a finalidade de avaliar a robustez do modelo. Além disso, uma extrapolação para nível nacional foi realizada, utilizando dados epidemiológicos para a obtenção do número de pacientes. Resultados: Foram selecionados 268 pacientes que iniciaram o tratamento até 2012. Desses, 65 foram elegíveis à descontinuação. A análise econômica mostrou uma economia de R$ 670.558,10 no primeiro ano, uma economia acumulada em cinco anos de R$ 3.665.355,98 e de R$ 66.517.232,80 no contexto institucional e nacional, respectivamente. A análise de sensibilidade foi favorável em todos os cenários propostos. Conclusões: A descontinuidade do tratamento da LMC mostrou-se, economicamente, uma importante oportunidade sob a perspectiva do sistema de saúde em flexibilizar novos investimentos tecnológicos e/ou ampliação de cesso, além da melhoria na qualidade de vida do paciente.

Objective: To assess the economic impact of discontinuing treatment of chronic myeloid leukemia (CML) with first or second line tyrosine kinase inhibitors (ITQs). Methods: The model included patients diagnosed with CML undergoing treatment with ITQs who started treatment until 2012, under eligible conditions in the year 2015. A 5-year time horizon was considered from the perspective of the public health system. Costs associated with treatment, such as medication, monitoring and handling adverse events were analyzed. The evaluation consisted of two scenarios, the reference scenario with continuous use of the drug and the comparator scenario with the interruption of drug treatment. Both scenarios considered the technologies available in the period from 2015 to 2019. The sensitivity analysis proposed variations in the scenarios in order to assess the robustness of the model. In addition, an extrapolation to the national level was performed, using epidemiological data to obtain the number of patients. Results: 268 patients who started treatment until 2012 were selected. Of these, 65 were eligible for discontinuation. The economic analysis showed savings of R$ 670,558.10 in the first year, accumulated savings in five years of R$ 3,665,355.98 and R$ 66,517,232.80 in the institutional and national context, respectively. The sensitivity analysis was favorable in all the proposed scenarios. Conclusions: The discontinuity of CML treatment proved to be, economically, an important opportunity from the perspective of the health system in making new technological investments and / or expanding access more flexible, in addition to improving the patient's quality of life

Efficacy of osettinib in the treatment of first-line tyrosine kinase inhibitor-resistant advanced lung adenocarcinoma and its effects on carcinoembryonic antigen and vascular endothelial growth factor levels / 中国基层医药

Objective:To investigate the efficacy of osettinib in the treatment of first-line tyrosine kinase inhibitor-resistant advanced lung adenocarcinoma and its effects on carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF) levels.Methods:Seventy-two patients with first-line tyrosine kinase inhibitor-resistant advanced lung adenocarcinoma (T790M test negative or rejected) who received treatment in Jinhua Guangfu Cancer Hospital from June 2017 to June 2019 were included in this study. They were randomly assigned to undergo either conventional pemetrexed plus cisplatin (control group, n = 36) or osimertinib mesylate (observation group, n = 36) for 4 successive weeks. Before and after 4 weeks of treatment, serum CEA and VEGF levels were measured. Curative effects were evaluated. Adverse reactions and 6-month, 1-year and 2-year survival rate were recorded. Results:Effective rate and disease-control rate in the observation group were 80.6% (29/36) and 94.4% (34/36) respectively, which were significantly higher than 58.3% (21/36) and 75.0% (27/ 36) in the control group ( χ2 = 4.193, 5.261, both P < 0.05). Before treatment, there were no significant differences in serum CEA and VEGF levels between the two groups (both P > 0.05). Compared with before treatment, serum CEA and VEGF levels were significantly increased after treatment (both P < 0.05). After treatment, serum CEA and VEGF levels in the observation group were (5.36 ± 0.33) U/mL and (121.56 ± 11.57) ng/L respectively, which were significantly lower than those in the control group [(8.25 ± 0.54) U/mL, (163.68 ± 14.59) ng/L, t = 27.399, 13.572, both P < 0.001]. The incidence of adverse reactions in the observation group was significantly lower than that in the control group [19.4% (7/36) vs. 44.4% (16/36), χ2 = 5.173, P = 0.011]. 6-month, 1-year and 2-year survival rate were 94.29%, 77.14% and 60.00% respectively, in the observation group and 91.43%, 54.29% and 34.29% respectively in the control group. There was no significant difference in 6-month overall survival rate between the two groups ( χ2 = 0.352, P = 0.251). 1-year and 2-year survival rate in the observation group were significantly higher than those in the control group ( χ2 = 4.058, P = 0.044; χ2 = 4.644, P = 0.031). Conclusion:Ositinib is effective in the targeted treatment of first-line tyrosine kinase inhibitor-resistant advanced lung adenocarcinoma. It can effectively decrease serum CEA and VEGF levels and prolong the survival of patients, thereby exhibiting a clinical application value.

Custo-efetividade do erlotinibe comparado ao gefitinibe para CPNPC com mutações EGFR no Inca / Cost-effectiveness of erlotinib compared to gefitinib for NSCLC with EGFR mutations at the Inca

Objetivo: O câncer de pulmão (CP), segundo dados da Organização Mundial de Saúde, é a neoplasia mais frequente e mais letal em homens e a segunda nas mulheres em todo o mundo. O CP compreende vários tipos histológicos, incluindo câncer de pulmão de pequenas células e os diferentes tipos de câncer de pulmão de não pequenas células (CPNPC). Esse subtipo representa cerca de 80% dos casos e compreende principalmente o adenocarcinoma. A terapia de escolha para tratamento de CPNPC com mutação no receptor do fator de crescimento epidérmico (EGFR) são os inibidores de tirosina quinase (ITKs), como erlotinibe e gefitinibe. Neste artigo avaliamos o custo-efetividade do erlotinibe comparado ao gefitinibe no tratamento de CPNPC. Métodos: Foi realizada uma análise de custo-efetividade sob a perspectiva de um hospital federal do Sistema Único de Saúde (SUS). Em um modelo de árvore de decisão, foram aplicados os desfechos de efetividade e segurança dos ITKs. Os dados clínicos foram extraídos de prontuários e os custos diretos, consultados em fontes oficiais do Ministério da Saúde. Resultados: O custo de 10 meses de tratamento, englobando o valor dos ITKs, procedimentos e manejo de eventos adversos, foi de R$ 63.266,76 para o erlotinibe e de R$ 39.594,72 para o gefitinibe. Os medicamentos apresentaram efetividade estatisticamente equivalente e diferença estatisticamente significativa para o desfecho de segurança, no qual o gefitinibe obteve melhor resultado. Conclusão: O gefitinibe, nesse contexto, é a tecnologia dominante quando os custos de tratamento são associados aos de manejo de eventos adversos.

Objective: According to the World Health Organization (WHO), lung cancer (LC) is the most common and lethal neoplasm in men and the second most common in women worldwide. The LC comprises several histological types, including small cell lung cancer and the different types of non-small cell lung cancer (NSCLC). This subtype represents about 80% of the cases and mainly comprises adenocarcinoma. The therapy of choice for epidermal growth factor receptor (EGFR) mutant NSCLC are tyrosine kinase inhibitors (TKI), like erlotinib and gefitinib. In this article, we evaluate the cost-effectiveness of erlotinib in comparison to gefitinib. Methods: A cost-effectiveness analysis was performed from the perspective of a Sistema Único de Saúde (SUS) federal hospital. In a decision tree model, the effectiveness and safety outcomes of TKIs were applied. The clinical data were extracted from the medical records and the direct costs consulted in official sources of the Ministry of Health. Results: The cost of 10 months of processing, encompassing the TKI value, procedures and resources of adverse events was R$ 63.266,76 for the year and R$ 39.594,72 for gefitinib. Forging cards have equal and statistically significant effectiveness for the safety outcome. Conclusion: Gefitinib, in this context, is a dominant technology when process costs are associated with those of managing adverse event.

Clinical efficacy analysis of pemetrexed combined with gefitinib in treatment of advanced non-small cell lung cancer after epidermal growth factor receptor-tyrosine kinase inhibitor drug resistance / 肿瘤研究与临床

Objective To investigate the clinical efficacy of pemetrexed alone or combined with gefitinib in treatment of advanced non-small cell lung cancer (NSCLC) after epidermal growth factor receptortyrosine kinase inhibitor (EGFR-TKI) drug resistance.Methods The clinical data of 80 patients with advanced NSCLC after EGFR-TKI drug resistance from August 2014 to April 2018 were retrospectively analyzed.They were divided into two groups according to their treatment regimens:40 patients received pemetrexed alone (the control group) and 40 patients received pemetrexed combined with gefitinib (the observation group).The recent clinical efficacy,adverse reactions and the survival time of both groups were compared.The count data was compared by using x2 test or Fisher exact test.Kaplan-Meier method was used to make survival analysis and log-rank method was used to detect.Results The total effective rate of the observation group was higher than that of the control group [70.0％ (28/40) vs.32.5％ (13/40),x2 =11.257,P =0.001].There was no statistical difference in the adverse reactions [17.5％ (7/40) vs.20.0％ (8/40),x2 =0.082,P =0.775].The median progression-free survival time and median overall survival time of the observation group were longer than those of the control group (6.5 months vs.3.5 months,15.5 months vs.8.5 months,all P ＜ 0.01).Conclusion Pemetrexed combined with gefitinib has a recent favorable effect in advanced NSCLC after EGFR-TKI drug resistance,including low incidence of adverse reactions and prolonged survival time,which is worthy of further application.

Custo-efetividade do pazopanibe comparado ao sunitinibe para câncer renal metastático na perspectiva de um hospital do Sistema Único de Saúde / Cost-effectiveness between pazopanib and sunitinib for metastatic renal cancer from the perspective of the Brazilian Unified National Health System / Costo-efectividad entre el pazopanib y el sunitinib para el cáncer renal metastásico desde la perspectiva del Sistema Único de Salud

Resumo: O câncer renal é a 13ª neoplasia mais frequente no mundo. Entre 2012 e 2016, representou 1,48% das mortes por câncer no Brasil. A terapia de escolha para o tratamento de câncer renal metastático são os inibidores de tirosina quinase (ITK), sunitinibe e pazopanibe. Este artigo avalia o custo-efetividade do pazopanibe comparado ao sunitinibe no tratamento de câncer renal metastático. Foi realizada uma análise de custo-efetividade sob a perspectiva de um hospital federal do Sistema Único de Saúde. No modelo de árvore de decisão foram aplicados os desfechos de efetividade e segurança dos ITK. Os dados clínicos foram extraídos de prontuários e os custos diretos consultados em fontes oficiais do Ministério da Saúde. O custo de 10 meses de tratamento, englobando o valor dos ITK, procedimentos e manejo de eventos adversos, foi de R$ 98.677,19 para o pazopanibe e R$ 155.227,11 para o sunitinibe. Os medicamentos apresentaram efetividade estatisticamente equivalente e diferença estatisticamente significativa para o desfecho de segurança, no qual o pazopanibe obteve o melhor resultado. O pazopanibe, nesse contexto, é a tecnologia dominante quando os custos de tratamento são associados aos de manejo de eventos adversos.

Abstract: Renal cancer is the 13th most frequent neoplasm in the world. From 2010 to 2014, renal cancer accounted for 1.43% of cancer deaths in Brazil. The treatment of choice for metastatic renal cancer is tyrosine kinase inhibitors (TKI) sunitinib and pazopanib. This article assesses cost-effectiveness between pazopanib and sunitinib in the treatment of metastatic renal cancer. A cost-effectiveness study was performed from the perspective of a federal hospital under the Brazilian Unified National Health System (SUS). TKI effectiveness and safety outcomes were applied to the decision tree model. Clinical data were extracted from patient charts, and direct costs were consulted from official Ministry of Health sources. The cost of 10 months of treatment, including the costs of the TKI, procedures and management of adverse events, was BRL 98,677.19 for pazopanib and BRL 155,227.11 for sunitinib. The drugs displayed statistically equivalent effectiveness and statistically different safety outcomes, with pazopanib displaying better results. In this setting, pazopanib is the dominant technology when the treatment costs are analyzed together with the costs of managing adverse events.

Resumen: El cáncer renal es la 13ª neoplasia más frecuente en el mundo. Entre 2010 y 2014, representó un 1,43% de las muertes por cáncer en Brasil. La terapia de elección para el tratamiento de cáncer renal metastásico son los inhibidores de tirosina quinasa (ITK), sunitinib y pazopanib. Este artículo evalúa el costo-efectividad entre pazopanib y sunitinib en el tratamiento de cáncer renal metastásico. Se realizó un análisis de costo-efectividad desde la perspectiva de un hospital federal del Sistema Único de Salud. En el modelo de árbol de decisión se aplicaron los desenlaces de efectividad y seguridad de los ITK. Los datos clínicos se extrajeron de registros médicos, y los costos directos consultados en fuentes oficiales del Ministerio de Salud. El costo de 10 meses de tratamiento, englobando el valor de los ITK, procedimientos y gestión de eventos adversos, fue de BRL 98.677,19 con el pazopanib y BRL 155.227,11 con el sunitinib. Los medicamentos presentaron efectividad estadísticamente equivalente y diferencia estadísticamente significativa para el desenlace de seguridad, en el que el pazopanib obtuvo el mejor resultado. El pazopanib, en este contexto, es la tecnología dominante cuando los costes de tratamiento están asociados a los de la gestión de eventos adversos.

Primary Extragastrointestinal Stromal Tumor of Retroperitoneum: Poor Response to Tyrosine Kinase Inhibitor

Gastrointestinal stromal tumors (GIST) are the most common sarcomas arising in the gastrointestinal tract. Stromal tumors arising outside the gastrointestinal tract are known as extragastrointestinal stromal tumors (EGIST). EGISTs may occur in omentum, mesentery, or retroperitoneum and are histologically and immunophenotypically similar to that in GISTs. EGISTs are very rare, so pathogenesis, incidence, and prognosis of EGISTs are not defined yet. In particular, there are a few reported literatures on the treatment of metastatic EGISTs. I report a case of a primary EGIST of the retroperitoneum with lung metastasis surgically removed and treated with tyrosine kinase inhibitor.

Clinical significance of serum levels of sFlt-1, AMY and hs-CRP in patients with acute pancreatitis / 中国医师杂志

Objective To investigate the dynamic changes of soluble fms-like tyrosine kinase 1 (sFlt-1),Amylase (AMY) and high sensitvie C reactive protein (hs-CRP) in the early diagnosis of acute pancreatitis (AP) and its clinical significance.Methods 72 patients with AP were selected and divided into mild group (n =45) and severe group (n =27).Another 30 healthy subjects in the same period were selected as control group (n =30).Serum sFlt-1 levels were measured by enzyme-linked immunosorbent assay (ELISA) on the 1st,3rd and 7th day after admission.Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score was used to assess acute physiology and chronic health status,and AMY and hsCRP levels were measured.Results Serum levels of sFlt-1,AMY and hs-CRP in the severe group were significandy higher than those in the mild group on the 1 st,3rd and 7th day after admission (all P ＜ 0.01).The levels of sFlt-1,AMY and hs-CRP in the mild group were significantly higher than those in the control group (all P ＜ 0.01).The scores of APACHE Ⅱ in the severe group were significantly higher than those in the mild group on the 1st,3rd and 7th day after admission (all P ＜ 0.01).There was a positive correlation between serum sFlt-1 level and AMY,hs-CRP,APACHE Ⅱ scores on the first day of admission (respectively r =0.738,P =0.00;r =0.563,P =0.000;r =0.233,P =0.028),on the third day of admission (respectively r =0.622,P =0.000;r =0.584,P =0.000;r =0.218,P =0.032),on the seventh day of admission (respectively r =0.593,P =0.000;r =0.547,P =0.000;r =0.227,P =0.030).Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of serum sFlt-1,AMY and hs-CRP were 0.918 (95％ CI:0.865-0.971,P =0.000),0.948 (95％ CI:0.908-0.989,P=0.000) and 0.789 (95％ CI:0.696-0.882,P=0.000),respectively.Conclusions The level of sFlt-1 in peripheral blood is significantly increased in patients with AP,which is closely related to the severity of AP.Dynamic monitoring of serum sFlt-1,AMY and hs-CRP has important clinical value in the diagnosis,treatment,severity and prognosis of AP.

Synthesis and protein tyrosine kinases inhibitory activity of substituted benzyl piperazine derivatives / 国际药学研究杂志

Objective Using substituted benzyl piperazine as the raw material to design and synthesize new piperazine deriva-tives with protein tyrosine kinase(PTK)inhibitory activity. Methods Benzoic acid was used as starting compound to synthesize a key intermediate,2-chloroethyl benzoate,and the target compounds were synthesized by further reaction of the key intermediate with different substituted benzyl piperazine derivatives.Enzyme-linked immunosorbent assay(ELISA)was used to test the PTK inhibitory activity of the compounds.Results Fifteen new compounds were synthesized and their structures were verified by IR,1H NMR,MS, and elemental analysis.The PTK inhibitory activity of 3h and 3o was stronger than that of the other compounds.Conclusion The syn-thetic method is simple,and the raw materials are cheap and readily available.Compounds 3h and 3o showed relatively higher PTK in-hibitory activities.

Chimeric antigen T-cell therapy combined with imatinib and chemotherapy in treatment of Philadelphia chromosome-like acute lymphoblastic leukemia with EBF1-PDGFRB-positive: report of one case and review of literature / 白血病·淋巴瘤

Objective To improve the understanding of the diagnosis and treatment of Philadelphia (Ph) chromosome-like acute lymphoblastic leukemia (ALL) with EBF1-PDGFRB-positive. Methods One case of Ph-like ALL with EBF1-PDGFRB-positive from the First Affiliated Hospital of Soochow University was reported. Whole exome sequencing was applied to detect the EBF1-PDGFRB fusion gene. Fluorescence in situ hybridization (FISH) was used to detect minimal residual disease. Comprehensive treatments including chemotherapy, imatinib and chimeric antigen T-cell (CAR-T) therapy were utilized. Results EBF1-PDGFRB fusion gene in the bone marrow samples was detected by using whole exome sequencing at early diagnosis. The rearrangement of PDGFRB showed continuous negative after comprehensive therapy. The patient achieved continuous molecular remission for 22 months. Conclusions The comprehensive treatments include combined chemotherapy, CAR-T therapy and tyrosine kinase inhibitor can promote the continuous of major molecular remission for EBF1-PDGFRB-positive Ph-like ALL patients.

Atypical Teratoid Rhabdoid Tumour : From Tumours to Therapies

Atypical teratoid rhabdoid tumours (ATRTs) are the most common malignant central nervous system tumours in children ≤1 year of age and represent approximately 1–2% of all pediatric brain tumours. ATRT is a primarily monogenic disease characterized by the bi-allelic loss of the SMARCB1 gene, which encodes the hSNF5 subunit of the SWI/SNF chromatin remodeling complex. Though conventional dose chemotherapy is not effective in most ATRT patients, high dose chemotherapy with autologous stem cell transplant, radiotherapy and/or intrathecal chemotherapy all show significant potential to improve patient survival. Recent epigenetic and transcriptional studies highlight three subgroups of ATRT, each with distinct clinical and molecular characteristics with corresponding therapeutic sensitivities, including epigenetic targeting, and inhibition of tyrosine kinases or growth/lineage specific pathways.

Expression of BDNF and TrkB in hippocampal microglia cells of poststroke depression rats / 中华老年心脑血管病杂志

Objective To study the expression of BDNF and TrkB in hippocampal microglia cells of poststroke depression (PSD) rats.Methods Forty healthy adult SD rats were randomly divided into normal group,depression group,stroke group and PSD group (10 in each group).Expression of BDNF and TrkB in OX42-marked hippocampal microglia cells of PSD rats was detected with immunofluorescence staining on day 29 and 57 after a MCAO model rats was established and a chronic stress depression model of rats was established by chronic unpredictable mild stress (CUMS) combined with separate breeding.Results The absorbance value of BDNF and TrkB was 83.35t5.74 and 82.35±5.74 respectively in PSD group on day 29 after the CUMS of rats was established,which was significantly lower than other 3 groups (P＜0.05),and was significantly higher in depression group than in stroke group (141.23±9.16 vs 133.31±7.89;141.23± 8.07 vs 128.62±6.92,P＜0.05).The absorbance value of BDNF and TrkB was 81.63±7.19 and 74.43±7.42 respectively in PSD group on day 57 after the CUMS of rats was established,which was lower than in other 3 groups,and was significantly lower in stroke group than normal group and depression group (93.36±7.56 vs 124.11±11.39、116.65±10.55,87.14±6.56 vs 112.58± 10.99、108.05±10.57,P＜0.05).Conclusion Hippocampal microglia cells play an important role in the pathogenesis of PSD by down-regulating the expression of BDNF and TrkB in PSD rats.

Atypical Teratoid Rhabdoid Tumour : From Tumours to Therapies

Atypical teratoid rhabdoid tumours (ATRTs) are the most common malignant central nervous system tumours in children ≤1 year of age and represent approximately 1–2% of all pediatric brain tumours. ATRT is a primarily monogenic disease characterized by the bi-allelic loss of the SMARCB1 gene, which encodes the hSNF5 subunit of the SWI/SNF chromatin remodeling complex. Though conventional dose chemotherapy is not effective in most ATRT patients, high dose chemotherapy with autologous stem cell transplant, radiotherapy and/or intrathecal chemotherapy all show significant potential to improve patient survival. Recent epigenetic and transcriptional studies highlight three subgroups of ATRT, each with distinct clinical and molecular characteristics with corresponding therapeutic sensitivities, including epigenetic targeting, and inhibition of tyrosine kinases or growth/lineage specific pathways.

Primary cutaneous amelanotic melanoma and gastrointestinal stromal tumor in synchronous evolution

Abstract: Gastrointestinal stromal tumor is rare digestive tract mesenchymal tumor, most often in the wall of the stomach. It is a benign neoplasm, but it can become malignant if not treated. We report a case of gastrointestinal stromal tumor that was discovered after abdominal ultrasonography during staging of a patient with primary cutaneous amelanotic melanoma. Mutation in the tyrosine kinase receptor could explain the development of two types of tumors in the same patient.

Expression and significance of estrogen receptor- β and tyrosine kinase receptor- B in endometriosis associated ovarian cancer / 中国医师进修杂志

Malignant transformation of ovarian endometriosis is known as endometriosis associated ovarian cancer (EAOC). However, the carcinogenic pathways by which EAOC develops remained poorly understood, and numerous studies found the risk factors of malignant transformation. Recent studies have provided evidence that estrogen receptor-β(ER-β) can influence the proliferation, motility and apoptosis of ovarian cancer cells. The signal pathway of tyrosine kinase receptor-B (TrkB)/brain-derived neurotrophic factor (BDNF) has a direct relation with the endometriosis, and its anti-anoikis plays a prerequisite role in proliferation of cancer. In the nervous system, estradiol and estrogen receptor can be combined through a variety of ways to promote BDNF/TrkB high expression and activity enhancement. Therefore,the relationship between high-risk factors of malignant transformation and ER-β expression and ER-β and TrkB/BDNF signal pathways need to be explored in EAOC.

Progression and clinical application of tyrosine kinase inhibitors for the treatment of chronic myelogenous leukemia / 中国医师杂志

Chronic myelogenous leukemia (CML) has a high proportion in hematologic malignancy.Past decade,the appearance and development of tyrosine kinase inhibitors (TKIs) is the milestone of the treatment of CML.TKIs have antitumor effect with inhibition of the phosphorylation of kinases and the downstream signal transduction.In recent years,many large medical institutions at home and abroad worked on clinical experiment researches to investigate the mechanism of TKIs and how to choose TKIs in CML patients.This work is of great significance to the clinic.