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Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase and its rearrangements occur in non-small cell lung cancer (NSCLC), resulting in signal dysregulation in kinase domain. As a new generation of potent ALK tyrosine kinase inhibitors (TKIs), Brigatinib was approved in China in March 2022 as a treatment for locally advanced or metastatic NSCLC patients with ALK rearrangement positive. Brigatinib significantly improved the survival, cranial efficacy and quality of life compared to Crizotinib in clinical trials. Brigatinib is generally well tolerated. Brigatinib has been one of the preferred treatments and an addition of options in ALK-rearranged NSCLC. Pulmonary toxicity is one of the adverse effects observed during the treatment of TKIs and deserves the intense attention of clinicians, despite of its low incidence rate. Pulmonary toxicity reported during the treatment of Brigatinib has shown distinct clinical presentations, such as early-onset (median time to onset, 2 days) and rapid tolerance and reversibility of symptoms. In view of this, the concept of early-onset pulmonary events (EOPEs) was proposed and established during the submission for regulatory review and approval. We focused on clinical characteristics, potential mechanism of etiology, and management strategies of EOPEs to provide clinicians evidence for better clinical decision support. .
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Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/genética , Calidad de Vida , Proteínas Tirosina Quinasas Receptoras , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
Objective To investigate the effect of chronic restraint stress on the expression of N6-methyladenosine (m6A)and related enzymes in the hippocampus of mice. Methods Twenty C57BL/6J male mice were randomly divided into control group and chronic restraint stress (CRS) group, the model group was given for 3 weeks chronic restraint stress to establish a mouse anxiety model. Open field test and elevated plus maze test were used to detect anxiety-like behavior; Immunohistochemistry and m6A RNA methylation assay were used to detect the expression changes of mouse hippocampal m6A; Western blotting and Real-time PCR were used to analyze hippocampal m6A related enzymes expression. Results 1.The behavioral results showed that, compared with the control group, the CRS group showed significantly reduced time spent in the center of the open field(P<0.01), the CRS group showed significantly reduced exploration time in the open arm of elevated plus maze (P<0.0001); 2. Immunohistochemical results showed that, compared with the control group, the hippocampal m6A content in the CRS group reduced significantly (P < 0.001); The results of the m6A RNA methylation assay showed that, compared with the control group, the CRS group showed significantly reduced amount of hippocampal m6A(P<0.05); 3. Real-time PCR results showed that the expression of hippocampal demethylase anaplastic lymphoma kinase B(AlkB) homolog 5(ALKBH5) (P<0.001) and fat mass and obestity associated protein(FTO) (P< 0.05) in the CRS group significantly up-regulated, the expression of methylase Wilms' tumour 1-associating protein (WTAP) (P<0.05) was significantly down-regulated compared with the control group; The expression of m6A methylation binding protein YTH domaincontaining family protein 3 (YTHDF3) (P < 0.05) and YTH domaincontaining protein 2 (YTHDC2) (P < 0.01) was significantly up-regulated. Western blotting result showed that, compared with the control group, the mouse hippocampal demethylase ALKBH5 (P < 0.05) and FTO (P < 0.05) expression in the CRS group significantly up-regulated, the expression of WTAP (P<0.01) was significantly down-regulated; m6A methylation binding protein YTHDF3 (P<0.01) and YTHDC2 (P<0.05) were significantly up-regulated. Conclusion In the anxiety model induced by chronic restraint stress, the expression of m6A in the hippocampus of mice is down-regulated. The mechanism may be related to the up-regulation of the m6A demethylase ALKBH5 and FTO or the down-regulation of the methylase WTAP.
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Background and Aim: Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphomas (ALK+-LBCLs) are aggressive CD20-negative lymphomas, accounting for <1% of diffuse LBCLs. Being rare and with peculiar immunophenotypic characteristics, these can be easily misdiagnosed. We present 11 cases of ALK+-LBCLs diagnosed over a period of 11 years at a tertiary care hospital in South India to analyze the clinical, morphological, and immunophenotypic profile of these tumors. Subjects and Methods: ALK+-LBCL cases diagnosed from September 2009 to August 2020 were included. Clinical details were obtained from stored electronic records and summarized. Available hematoxylin and eosin (H and E) stained slides and immunohistochemistry slides were reviewed and observations tabulated. Results: Eleven patients (nine males and two females) were diagnosed with ALK+-LBCLs in the study period with seven presenting primarily with extranodal disease manifestations. Tumors in the lymph nodes showed diffuse architecture effacement and variable sinusoidal invasion. All tumors showed immunoblastic and plasmablastic-type large lymphoid cells with scattered anaplastic/multinucleate large cells, including rare Reed–Sternberg-like cells. Cytoplasmic granular ALK-1 staining, CD20 negativity, and immunohistochemical features of plasmablastic differentiation were noted in all. Of eight patients treated, only one achieved remission with multi-agent chemotherapy but relapsed after 6 months. Two patients died of disease and five others had progressive/persistent disease and were lost to follow-up. Conclusion: Although rare, these tumors should always be in the differential diagnoses of tumors with plasmablastic and immunoblastic morphology, especially in extranodal sites to avoid diagnostic delay/misdiagnosis.
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Background: Anaplastic lymphoma kinase (ALK)?rearranged nonsmall cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Tyrosine kinase inhibitor crizotinib, an anticancer drug acting as an ALK inhibitor, has shown remarkable response in ALK?positive NSCLC. The aim of our study is to explore the adverse events (AEs) of patients on crizotinib therapy and analyze the predictability of AEs for better survival or response on NSCLC patients. Methods: The medical records of our ALK?positive metastatic NSCLC patients who applied between years 2013 and 2018 had been reviewed retrospectively. ALK positivity of all patients had been detected by fluorescence in situ hybridization and no other driver mutations were present. Patient demographics, performance status, smoking history, previous treatments, metastatic sites, and AEs were recorded for further analyses. Results: Thirty?six ALK?positive metastatic NSCLC patients were included in the study. Median follow?up was 30.1 months. Median progression?free survival (PFS) for patients who developed hepatic, cardiac, or endocrine toxicities was similar when compared to patients who did not develop. Although there was a numeric median PFS difference between patients who did develop visual disorders (18.4 months) and did not develop visual disorders (15.5 month), this was not regarded as statistically significant. However, median PFS of the patients who developed neutropenia upon crizotinib treatment (31.9 months) was found to be more favorable than the patients with normal neutrophil counts (12.8 months) (P = 0.026). Conclusion: Neutropenia under crizotinib treatment was found to be associated with improved PFS suggesting that neutropenia might be an important determinant in treatment and survival strategies.
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BACKGROUND@#At present, the research progress of targeted therapy for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene mutations in lung adenocarcinoma is very rapid, which brings new hope for the treatment of advanced lung adenocarcinoma patients. However, the specific imaging and pathological features of EGFR and ALK gene mutations in adenocarcinoma are still controversial. This study will further explore the correlation between EGFR, ALK gene mutations and imaging and pathological features in invasive lung adenocarcinoma.@*METHODS@#A total of 525 patients with lung adenocarcinoma who underwent surgery in our center from January 2018 to December 2019 were included. According to the results of postoperative gene detection, the patients were divided into EGFR gene mutation group, ALK gene mutation group and wild group, and the EGFR gene mutation group was divided into exon 19 and exon 21 subtypes. The pathological features of the mutation group and wild group, such as histological subtype, lymph node metastasis, visceral pleural invasion (VPI) and imaging features such as tumor diameter, consolidation tumor ratio (CTR), lobulation sign, spiculation sign, pleural retraction sign, air bronchus sign and vacuole sign were analyzed by univariate analysis and multivariate Logistic regression analysis to explore whether the gene mutation group had specific manifestations.@*RESULTS@#EGFR gene mutation group was common in women (OR=2.041, P=0.001), with more pleural traction sign (OR=1.506, P=0.042), and had little correlation with lymph node metastasis and VPI (P>0.05). Among them, exon 21 subtype was more common in older (OR=1.022, P=0.036), women (OR=2.010, P=0.007), and was associated with larger tumor diameter (OR=1.360, P=0.039) and pleural traction sign (OR=1.754, P=0.029). Exon 19 subtype was common in women (OR=2.230, P=0.009), with a high proportion of solid components (OR=1.589, P=0.047) and more lobulation sign (OR=2.762, P=0.026). ALK gene mutations were likely to occur in younger patients (OR=2.950, P=0.045), with somking history (OR=1.070, P=0.002), and there were more micropapillary components (OR=4.184, P=0.019) and VPI (OR=2.986, P=0.034) in pathology.@*CONCLUSIONS@#The EGFR and ALK genes mutated adenocarcinomas have specific imaging and clinicopathological features, and the mutations in exon 19 or exon 21 subtype have different imaging features, which is of great significance in guiding the clinical diagnosis and treatment of pulmonary nodules.
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Anciano , Femenino , Humanos , Adenocarcinoma del Pulmón/genética , Quinasa de Linfoma Anaplásico/genética , Receptores ErbB/genética , Genes erbB-1 , Neoplasias Pulmonares/patología , Mutación , Tomografía Computarizada por Rayos X/métodosRESUMEN
The incidence of inflammatory myofibroblastic sarcoma is low, and bladder origin is more rare. We reported a 58-year-old patient with painless gross hematuria for one week. Total abdominal CT examination showed soft tissue mass in the anterior wall of the bladder, which was considered as bladder cancer, and bladder tumor resection was performed. Postoperative pathology showed inflammatory myofibroblastic sarcoma. Therefore, radical cystectomy was performed because of the high degree of malignancy. There was no recurrence during 3 years follow-up.
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Objective:To investigate the effects of autophagy-mediated crizotinib resistance on cancer stem-like cell subsets in anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALK + ALCL). Methods:The preliminary research of our group divided ALK + ALCL Karpas299 cell line into two subgroups: reporter unresponsive (RU) and reporter responsive (RR) cells through the implantation of Sox2 reporter genes, among which the RR cells had the characteristics of stem cells. Fluorescent labeled LC3 overexpressing RR and RU cells (RR-LC3 and RU-LC3) were constructed by lentiviral transfection technique, and the transfection efficiency was verified by using Western blotting and flow cytometry. RU-LC3 and RR-LC3 were treated with crizotinib at different concentrations (0, 250, 500, 1 000 nmol/L). The RED and GEN signals were detected by using double-signal flow cytometry to observe autophagy flux (RED represents the red signal B695 of the next generation of far-red fluorescent protein TagFP635 mKate; GEN represents the green signal from pH-sensitive GFP variant pHluorin B530), and the RED to GEV ratio represents autophagy flux. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect autophagy related genes ULK1, WIPI1 and LC3B mRNA expression levels in cells. The effects of different concentrations of crizotinib (250, 500, 1 000 nmol/L) combined with chloroquine (5, 10 μmol/L) on the cell survival were detected by using MTS assay. Results:RU-LC3 and RR-LC3 cells with overexpression of LC3 were successfully constructed. After induction of 250, 500 and 1 000 nmol/L crizotinib, the RED to GEN ratio in RU-LC3 cells was 1.135±0.017, 1.453±0.017 and 1.755±0.021, respectively; the RED to GEN ratio in RR-LC3 cells was 1.193±0.018, 2.116±0.013 and 3.307±0.189, respectively; the RED to GEN ratio in RU-LC3 cells and RR-LC3 cells showed a dose-dependent manner. The RED to GEN ratio in RR-LC3 cells was higher than that in RU-LC3 cells when treated with same concentrations of crizotinib, and the differences were statistically significant (all P < 0.01). The autophagy flux of RR-LC3 cells was larger than that of RU-LC3 cells. When treated without crizotinib, mRNA relative expression levels of ULK1, WIPI1 and LC3B in RR cells were higher than those in RU cells (1.69±0.05 vs.1.01±0.02, t = -1.62, P < 0.01; 1.24±0.04 vs. 1.03±0.05, t = -2.11, P < 0.01; 1.70±0.22 vs. 1.02±0.05, t = -1.74, P = 0.033). In the absence of chloroquine, the half-inhibitory concentration ( IC50) of crizotinib in RR cells was higher than that of RU cells (950 nmol/L vs. 709 nmol/L). After treated with chloroquine, IC50 of RU cells did not change, while IC50 of RR cells was decreased with the increase of chloroquine concentration. Conclusions:Compared with RU cells, autophagy reaction of cancer stem-like RR cells is more rapid and intense, which is considered to be one of the important reasons for their resistance to crizotinib.
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Objective:To explore the clinical charateristics and prognostic factors of patients with primary systemic anaplastic large cell lymphoma (ALCL).Methods:The clinicopathological data of 31 patients with newly treated primary systemic ALCL in Liaoning Cancer Hospital from January 2010 to December 2020 were retrospectively analyzed. Kaplan-Meier method was used to make survival analysis and log-rank test was performed. Multivariate analysis of factors influencing overall survival (OS) was performed by using Cox proportional hazards model.Results:Among 31 patients, there were 19 males and 12 females, with a median age of 47 years old, ranging from 16 to 74 years old. There were 18 (58.1%) patients with B symptoms, 16 (51.6%) patients with increased platelet count, 22 (71.0%) patients with Ann Arbor stage Ⅲ-Ⅳ. Until the end of follow-up, 22 cases survived and 9 cases died; the 5-year OS rate was 70.9%, and the median OS time was not reached. The 5-year OS rate of patients receiving CHOPE chemotherapy regimen was higher than that of patients receiving CHOP and other chemotherapy regimens, and the difference was statistically significant ( P = 0.049). There were statistically significant differences in the 5-year OS rates of patients with different platelet count, international prognostic index (IPI) score, chemotherapy regimens and with or without B symptoms (all P < 0.05). Multivariate analysis indicated that IPI score was an independent factor affecting OS ( HR = 2.194, 95% CI 1.078-4.465, P = 0.030). Conclusions:Most primary systemic ALCL patients are diagnosed at advanced stage and it is more common in males. Most patients have B symptoms and high platelet count. IPI score is an important prognostic factor, and CHOPE regimen may be a good choice of the first-line chemotherapy.
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The clinical data of a child with anaplastic lymphoma kinase positive histiocytosis (ALK+ H) diagnosed in April 2020 by Kunming Children′s Hospital were retrospectively analyzed.The male child was 4 months and 29 days old and had multiple nodules throughout the body since 1 week after birth.Skin sarcoidosis examination showed non-Langerhans cell histiocytosis, and immunohistochemistry showed ALK (+ ), CD1a (-), and CD 163(+ ). Therefore, this patient was diagnosed as ALK+ H, which was very rare in clinical practice.Previously reported cases mainly showed soft tissue nodules or thrombocytopenia with anemia.In addition to multiple nodules throughout the body, this patient also had elevated platelets, neutropenia, and abnormal liver function, which was different from previous reports.Hence, this case could be used as a supplement to the disease database.
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Due to the high incidence and fatality rate of lung cancer, more and more attention is paid to the treatment model of lung cancer. Non-small cell lung cancer (NSCLC) accounts for about 4/5 of the total number of lung cancer patients, and the combination of anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) is found in 3%-7% of all cases. The treatment is mainly targeted therapy. The known targeted drugs for ALK fusion-positive NSCLC have been studied for the fourth generation, providing patients with a variety of medication options; in particular, the research on the fourth-generation drugs TPX-0131 and NUV-655 has brought new hopes to the majority of third-generation targeted drug-resistant patients. At present, China is also working hard to develop new domestic inhibitors, which will provide new drug options for Chinese patients with ALK-positive advanced NSCLC. This article will review its targeted therapy and the latest research, hoping to provide a reference for targeted drug selection.
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The mutation rate of anaplastic lymphoma kinase (ALK) in patients with non-small cell lung cancer is 3% to 7%. Due to its low mutation rate and better long-term survival compared with epidermal growth factor receptor-positive non-small cell lung cancer patients, therefore, it's called "diamond mutation". At present, there are three generations of ALK tyrosine kinase inhibitor (TKI) drugs in the world. The first-generation ALK-TKI drug approved in China is crizotinib, and the second-generation drugs are alectinib, ceritinib and ensartinib. Among them, ensartinib is an ALK-TKI domestically developed, and its efficacy is similar to that of alectinib. The main adverse event is transient rash, and compliance to ensartinib is better from the perspective of long-term survival of patients. The manifestation of rash caused by ensartinib is different from that of other ALK-TKI drugs. In order to facilitate clinical application and provide patients with more treatment options, under the guidance of the Committee of Cancer Rehabilitation and Palliative Care of China Anti-Cancer Association, this article collects and summarizes the common adverse reactions of ensartinib. Based on the clinical practice, a clear adverse classification and specific treatment plan are formulated, in order to provide a corresponding reference for clinicians to make more comprehensive clinical decisions.
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Humanos , Quinasa de Linfoma Anaplásico , Carbazoles/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Consenso , Exantema/tratamiento farmacológico , Neoplasias Pulmonares/patología , Piperazinas , Inhibidores de Proteínas Quinasas/efectos adversos , PiridazinasRESUMEN
OBJECTIVE To eva luate the economy of loratinib versus crizo tinib in the first-line treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC)from the perspective of China ’s health system , and to provide reference for the product pricing and related medical decisions of the drug in other regions of China except for Hong Kong. METHODS Markov model and partition survival model both constructed based on the CROWN data (the simulation time limit was 10 years and the cycle period was 4 weeks);the quality adjusted life year (QALY)was used as the outcome index to calculate the incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis ,probability sensitivity analysis and scenario analysis were used to verify the robustness of the results. RESULTS The basic analysis results based on Markov model showed that compared with crizotinib group ,the per capita cost of loratinib group increased by 17 867 588.63 yuan,the per capita utility increased by 1.76 QALYs,and the ICER was 10 152 038.99 yuan/QALY. The basic analysis results based on the partition survival model showed that compared with the crizotinib group ,the Δ 基金项目:江苏省博士后科研资助计划项目(No.2021K496C); per capita cost of loratinib group increased by 18 009 592.54 2020年度高校哲学社会科学研究一般项目(No.2020SJA0070) yuan,the per capita utility increased by 1.74 QALYs,and the *硕士研究生 。研究方向 :药物经济学 、卫生经济与政策 。 E-mail:sunlei_cpu@163.com ICER was 10 350 340.54 yuan/QALY. The results of one-way # 通信作者:教授,博士生导师。研究方向:药物经济学、卫生经 sensitivity analysis of the two models both showed that 济与政策。E-mail:ma86128@sina.com progression-free survival (PFS)state utility v alue,progression- ·1102· China Pharmacy 2022Vol. 33 No. 9 中国药房 2022年第33卷第9期 disease(PD)state utility value and loratinib cost had great influence on the results. The results of probability sensitivity analysis showed that when 1-3 times of China ’s per capita GDP in 2020 was taken as the willingness to pay threshold ,the probability of loratinib being economical was 0. The recommended unit price of loratinib per 100 mg was 657.10-815.60 yuan. CONCLUSIONS For patients with ALK-positive advanced NSCLC ,loratinib is more effective than crizotinib in the first-line treatment ,but it is not economical under the current price ;reasonably lowering the price of loratinib can increase the probability of its economy.
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BACKGROUND@#Anaplastic lymphoma kinase (ALK) is an important therapeutic target for advanced non-small cell lung cancer (NSCLC). In recent years, with the emergence of several ALK tyrosine kinase inhibitors (TKI), the overall survival (OS) of ALK fusion positive patients is gradually extended. This paper reports the treatment of a late stage non-small cell lung cancer (NSCLC) patient with ALK fusion positive for more than 5 years, and analyzes the treatment process and effect evaluation, so as to provide experience for the follow-up treatment of patients.@*METHODS@#The diagnosis and treatment process of a patient with advanced ALK fusion mutation positive lung cancer admitted to the third ward of Department of oncology, Chifeng hospital, Inner Mongolia on July 3, 2015 was retrospectively analyzed.@*RESULTS@#A 42 years old male patient was admitted to our department on July 3, 2015 for "intermittent cough, chest tightness for 2 months, diagnosed with lung adenocarcinoma for 1 day". Imaging examination showed a space occupying lesion in the left lower lobe of the lung, accompanied by mediastinal lymphadenopathy and left encapsulated pleural effusion. Bronchoscopic pathology showed non-small cell carcinoma, and adenocarcinoma was tentatively suggested.@*DIAGNOSIS@#left lower lobe adenocarcinoma T1bN2M1a stage IV. Fluorescence in situ hybridization (FISH) indicated the translocation of ALK (2p23) chromosome. After 2 cycles of docetaxel+cisplatin (DP) regimens chemotherapy, disease progression occurred, so we used 6 cycles of pemetrexed+carboplatin to apply combination chemotherapy, 4 cycles of pemetrexed monotherapy were used after that. The efficacy evaluation: PR. On April 9, 2016, the patient was treated with crizotinib. In August 2019, multiple intracranial metastases were found and whole brain radiotherapy was given. Since September 4, 2019, oral administration of nsatinib has been carried out. As of March 1, 2021, the patients were followed up well.@*CONCLUSIONS@#The advanced ALK fusion positive lung adenocarcinoma patients, though the first-line and the second-line chemotherapy, and the follwing application of ALK-TKI treatment, has procured a total OS has reached 68 months, and the current follow-up is good.
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Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure-activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties.
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The protein tyrosine phosphatase Src homology phosphotyrosyl phosphatase 2 (SHP2) is implicated in various cancers, and targeting SHP2 has become a promising therapeutic approach. We herein described a robust cross-validation high-throughput screening protocol that combined the fluorescence-based enzyme assay and the conformation-dependent thermal shift assay for the discovery of SHP2 inhibitors. The established method can effectively exclude the false positive SHP2 inhibitors with fluorescence interference and was also successfully employed to identify new protein tyrosine phosphatase domain of SHP2 (SHP2-PTP) and allosteric inhibitors. Of note, this protocol showed potential for identifying SHP2 inhibitors against cancer-associated SHP2 mutation SHP2-E76A. After initial screening of our in-house compound library (∼2300 compounds), we identified 4 new SHP2-PTP inhibitors (0.17% hit rate) and 28 novel allosteric SHP2 inhibitors (1.22% hit rate), of which SYK-85 and WS-635 effectively inhibited SHP2-PTP (SYK-85: IC
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Lung cancer is a malignant tumor with high incidence rate and mortality rate in China and even the whole world, of which non-small cell lung cancer accounts for about 80%. Anaplastic lymphoma kinase (ALK) gene mutation accounts for about 5%. Alectinib, ALK-tyrosine kinase inhibitor (ALK-TKI), has great performance in clinical. The early detection and treatment of adverse drug reactions can greatly improve clinical benefits. This paper reports a patient of ALK positive non-small cell lung cancer was admited to Baotou Central Hospital in April 2020. The diagnosis and treatment was retrospectively analyzed, and the literature was reviewed. .
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Humanos , Quinasa de Linfoma Anaplásico/genética , Antineoplásicos/uso terapéutico , Carbazoles/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/secundario , Neoplasias Pulmonares/patología , Mutación , Piperidinas/uso terapéutico , Neoplasias Pleurales/secundario , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
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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Humanos , Carcinoma de Pulmón de Células no Pequeñas , Crizotinib , Neoplasias Pulmonares/genética , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidoresRESUMEN
Objective: To investigate the effect of alectinib in the treatment of brain metastases from anaplastic lymphoma kinase(ALK)positive non-small cell lung cancer (NSCLC). Methods: Thirty-four cases of ALK-positive NSCLC in Tianjin Medical University Cancer Institute and Hospital, between August 2016 to October 2019, were retrospectively analyzed. Thirteen cases received first-line single drug therapy (600 mg PO bid) of Alectinib. 7 cases (53.8%) were male, 6 cases were female (46.2%), the median age was 51 (35-72). The Kaplan-Meier method was used to examine progression-free survival (PFS). Results: The median progression-free survival (mPFS) of the alectinib group was 24.5 months, and the adverse drug reactions were mild. Conclusions: The use of alectinibas first-line treatment after the local treatment of measurable intracranial lesions significantly increased the PFS of patients with brain metastases from ALK-positive NSCLC.
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Objective:To investigate the efficacy of anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKI) in treatment of inflammatory myofibroblastic tumor (IMT).Methods:The clinicopathological data of one recurrent abdominal IMT patient in Renmin Hospital of Wuhan University in 2018 were retrospectively analyzed. The clinicopathological and molecular characteristics, ALK-TKI treatment efficacy and prognosis of 41 patients with IMT reported in the literature from January 2010 to August 2020 were systematically reviewed.Results:This patient with abdominal IMT in Renmin Hospital of Wuhan University was a 27-year-old female who relapsed 2 months after surgery. Chemotherapy combined with bevacizumab was ineffective. After oral administration of crizotinib, the condition resolved after 1 month, and complete remission (CR) was achieved after 29 months. The median age of onset of 41 IMT cases reported in the literature was 22 years old (0-61 years old), of which 32 cases (78.0%) had multiple organ involvement, all of which had recurrence or metastasis. There were 38 cases of ALK mutation and 3 cases of TFG-ROS1 fusion gene-positive. Thirty-four patients treated with crizotinib in the first-line treatment of ALK-TKI, and the median resistance time of crizotinib was 8 months (2-48 months). The total clinical benefit rate of ALK-TKI was 85.3% (29/34), and 20 patients achieved CR. The median time for the first CR was 11 months (4-36 months), and the median duration time of medication for CR patients was 19.5 months (2-60 months). The median progression-free survival (PFS) time of 24 patients who underwent surgery and/or chemotherapy and radiotherapy was 4 months (1-45 months); after progression, ALK-TKI treatment was performed, and the median PFS time was 14 months (3-62 months).Conclusions:IMT is a true neoplasm with characteristics of recurrence and metastasis. Reasonable combination of ALK-TKI with surgery, radiotherapy and chemotherapy can improve the prognosis of IMT patients.
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Objective To explore the characteristics of ALK fusion gene in patients with primary lung adenocarcinoma in Gannan region, with hopes of scientifically guiding such patients towards selecting targeted drugs. Methods 5′/3′ imbalance strategy for qRT-PCR was used to detect the expression of ALK fusion gene in 233 cases of primary pulmonary adenocarcinoma and the clinical pathological characteristics were analyzed. Results The expression rate of ALK fusion genes was 9.01% (21/233). The expression rate of ALK fusion gene in female and N1-3 patients was significantly higher than that in male and N0 patients (P < 0.05); The expression rate of ALK fusion gene in patients with no smoking history, age < 55 years, M1 stage and fresh biopsy specimens was relatively high (P > 0.05); The expression of ALK fusion gene was not correlated with TNM stage, T stage, surgical treatment or tumor distribution location (P > 0.05). Moreover, in the subgroup analysis of 153 M1-stage cases, no correlation was found between the expression of ALK fusion gene and the metastasis of common sites of lung cancer (bone, brain, opposite lung, pleural dissemination adrenal glands and liver) (P > 0.05). Conclusion The expression rate of ALK fusion gene in primary lung adenocarcinoma in Gannan region is relatively high, which is common in female patients with lymph node metastasis.