ALK, anaplastic lymphoma kinase

ALK,间变性淋巴瘤激酶
  • 文章类型: Journal Article
    未经授权:附睾睾丸炎(EO)是附睾和同侧睾丸的疾病。布鲁氏菌附睾-睾丸炎(BEO)是一种罕见的睾丸和附睾局部感染,在所有布鲁氏菌病患者中约有2-14%是由于尿液布鲁氏菌清除或血液传播的败血症转移所致。
    UNASSIGNED:在2018年1月至2021年6月期间,50名发烧患者,发冷,肿胀,睾丸疼痛(睾丸)被提到我们的中心。在这些人中,使用了两种方法来治疗布鲁氏菌睾丸-睾丸炎。7例患者静脉注射庆大霉素和强力霉素,而其余43例患者在该组合中加入了利福平。静脉给予庆大霉素7天,其他药物使用45天。通过监测疾病的症状和体征,对所有患者进行6个月的随访。
    未经证实:在转诊到我们诊所之前,没有一个患者被诊断为布氏杆菌病。43例患者成功治疗。静脉注射庆大霉素,强力霉素和利福平,而7例患者使用完全治疗。静脉注射庆大霉素和强力霉素。两个治疗组分别住院7.56±3.45(3-23)天和10.14±1.77(8-13)天,分别。治疗失败,药物副作用,在6个月的随访期内,未观察到任何病例的疾病并发症。
    未经证实:在非特异性附睾-睾丸炎的鉴别诊断中,医生应警惕布鲁氏菌附睾-睾丸炎(BEO),尤其是在疾病流行的地区。BEO的诊断延迟或管理不当可能导致并发症。
    UNASSIGNED: Epididymo-orchitis (EO) is a disease of both the epididymis and ipsilateral testis. Brucellar epididymo-orchitis (BEO) is an uncommon localized infection of the testis and epididymis which occurs in about 2-14 % of all patients with brucellosis as a result of urine Brucella removal or due to blood-borne septic metastasis.
    UNASSIGNED: Between January 2018 and June 2021, 50 patients with fever, chills, swelling, and pain of the testicle (testicles) were referred to our center. Two approaches were used for the treatment of brucellarepididymo-orchitis among these individuals. Intravenous Gentamicin and Doxycycline were used in seven cases, while Rifampicin was added to this combination for the remaining 43 patients. Intravenous Gentamicin was administered for 7 days and the other drugs were used for 45 days. All patients were followed up for six months by monitoring the symptoms and signs of the disease.
    UNASSIGNED: None of the patients had been diagnosed with brucellosis before referral to our clinic. 43 patients were successfully treated by. Intravenous Gentamicin, Doxycycline and Rifampicin, whereas seven patients were fully treated using. Intravenous Gentamicin and Doxycycline. The two therapeutic groups were hospitalized for 7.56 ± 3.45 (3-23) and 10.14 ± 1.77 (8-13) days, respectively. Treatment failure, drug side effects, and disease complications were not observed in any of the cases over a 6-month follow-up period.
    UNASSIGNED: Physicians should be alert regarding Brucellarepididymo-orchitis (BEO) within the differential diagnosis of nonspecific epididymo-orchitis, especially in regions where the disease is endemic. Delay in diagnosis or inappropriate management of BEO may result in complications.
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  • 文章类型: Journal Article
    未经证实:转移性非小细胞肺癌中的间变性淋巴瘤激酶(ALK)易位(3%至7%)可预测对ALK抑制剂的反应(例如,阿列替尼,第一行),5年生存率为60%,中位无进展生存期为34.8个月。尽管阿来替尼的总体毒性率是可以接受的,无法解释的不良事件,包括水肿和心动过缓,可能表明潜在的心脏毒性。
    非ASSIGNED:本研究的目的是调查阿来替尼的心脏毒性和暴露毒性关系。
    UNASSIGNED:在2020年4月至2021年9月之间,纳入了53例接受阿来替尼治疗的ALK阳性非小细胞肺癌患者。在2020年4月之后开始使用alectinib的患者在开始时接受了心脏检查,在心脏肿瘤门诊患者的6个月和1年时。已经接受alectinib>6个月的患者接受1次心脏评估。心动过缓,水肿,收集阿来替尼严重毒性(导致剂量调整的≥3级和≥2级不良事件)数据.阿莱替尼稳态谷浓度用于暴露毒性分析。
    UNASSIGNED:所有接受治疗心脏评估的患者的左心室射血分数保持稳定(n=34;中位数为62%;IQR:58%-64%)。22例患者(42%)发生了阿来替尼相关的心动过缓(6例有症状的心动过缓)。一名患者因严重症状性心动过缓而接受了起搏器植入。严重毒性与阿来替尼平均Ctugh高出35%显著相关(728比539ng/mL,SD=83ng/mL;单侧P=0.015)。
    未经证实:没有患者出现左心室射血分数降低的迹象。阿莱替尼引起的心动过缓比以前报道的更多(42%),并有一些严重的症状性心动过缓。具有严重毒性的患者通常具有高于治疗阈值的升高的暴露。
    UNASSIGNED: Anaplastic lymphoma kinase (ALK) translocations in metastatic non-small cell lung cancer (3% to 7%) predict for response to ALK-inhibitors (eg, alectinib, first line), resulting in a 5-year survival rate of ∼60% and median progression-free survival of 34.8 months. Although the overall toxicity rate of alectinib is acceptable, unexplained adverse events, including edema and bradycardia, may indicate potential cardiac toxicity.
    UNASSIGNED: This study\'s aim was to investigate the cardiotoxicity profile and exposure-toxicity relationship of alectinib.
    UNASSIGNED: Between April 2020 and September 2021, 53 patients with ALK-positive non-small cell lung cancer treated with alectinib were included. Patients starting with alectinib after April 2020 underwent a cardiac work-up at start, at 6 months and at 1 year at the cardio-oncology outpatients\' clinic. Patients already receiving alectinib >6 months underwent 1 cardiac evaluation. Bradycardia, edema, and severe alectinib toxicity (grade ≥3 and grade ≥2 adverse events leading to dose modifications) data were collected. Alectinib steady-state trough concentrations were used for exposure-toxicity analyses.
    UNASSIGNED: Left ventricular ejection fraction remained stable in all patients who underwent an on-treatment cardiac evaluation (n = 34; median 62%; IQR: 58%-64%). Twenty-two patients (42%) developed alectinib-related bradycardia (6 symptomatic bradycardia). One patient underwent a pacemaker implantation for severe symptomatic bradycardia. Severe toxicity was significantly associated with a 35% higher alectinib mean Ctrough (728 vs 539 ng/mL, SD = 83 ng/mL; 1-sided P = 0.015).
    UNASSIGNED: No patients showed signs of a diminished left ventricular ejection fraction. Alectinib caused more bradycardia than previously reported (42%) with some instances of severe symptomatic bradycardia. Patients with severe toxicity generally had an elevated exposure above the therapeutic threshold.
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  • 文章类型: Case Reports
    一名抗核抗体阴性的非小细胞肺癌患者在免疫检查点抑制剂(ICI)给药后因呼吸困难而入院。计算机断层扫描(CT)显示复杂的放射学特征,包括胸膜下和基底占优势的网状阴影,囊性结构和支气管血管周围巩固。尽管我们在诊断为ICI相关性肺炎的情况下用大剂量类固醇治疗他,患者出现肺炎急性加重,伴有进行性纤维化和体积减少.重新评估在ICI施用前收集的血清中鉴定了抗氨酰基-tRNA合成酶抗体。此病例强调了重新评估发生ICI相关性肺炎且具有非典型放射学特征的患者先前存在的自身免疫性疾病的重要性。
    A man with non-small-cell lung cancer who was negative for anti-nuclear antibodies was admitted for dyspnea after immune checkpoint inhibitor (ICI) administration. Computed tomography (CT) showed complexed radiologic features, including subpleural and basal predominant reticular shadow with cystic structures and peribronchovascular consolidation. Although we treated him with high-dose steroid under a diagnosis of ICI-related pneumonitis, he developed acute exacerbation of pneumonitis with progressive fibrosis and volume loss. A re-evaluation identified anti-aminoacyl-tRNA synthetase antibody in the serum collected before ICI administration. This case highlights the importance of re-evaluating pre-existing autoimmune disorders in patients who develop ICI-related pneumonitis with atypical radiologic features.
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  • 文章类型: Case Reports
    未经批准:阿莱替尼,一个非常强大的,高度选择性,脑穿透性间变性淋巴瘤激酶(ALK)抑制剂现在是转移性ALK阳性非小细胞肺癌(NSCLC)患者的一线治疗方法.
    UNASSIGNED:我们报告了一名74岁的非裔美国女性在阿来替尼开始治疗转移性非小细胞肺癌后发生气腹的罕见病例。患者在开始阿来替尼后约2周出现腹痛。她血液动力学稳定,影像学显示气腹。患者非手术治疗成功。
    未经证实:表现为气腹的胃肠道穿孔是阿来替尼的一种非常罕见的并发症。据我们所知,我们的患者仅是自批准以来文献中报告的第二例。并发症可能归因于胃肠道中的快速肿瘤消退。如果可能,应尝试非手术管理。
    UNASSIGNED:肿瘤学家在对转移性NSCLC患者进行细胞毒性化疗时,应该意识到胃肠道穿孔的风险。多学科方法对于在该患者人群中适当地个性化护理至关重要。
    UNASSIGNED: Alectinib, a highly potent, highly selective, brain-penetrant anaplastic lymphoma kinase (ALK) inhibitor is now the first line therapy for patients with metastatic ALK-positive non small cell lung cancer (NSCLC).
    UNASSIGNED: We report a rare case of pneumoperitoneum following alectinib initiation for metastatic non small cell lung cancer in a 74-year-old African American female. Patient developed abdominal pain approximately 2 weeks after starting alectinib. She was hemodynamically stable, and imaging revealed pneumoperitoneum. Patient was successfully managed non-operatively.
    UNASSIGNED: Gastrointestinal perforation presenting as pneumoperitoneum is a very rare complication of alectinib. To our knowledge our patient is only the second case to be reported in the literature since its approval. The complication is likely attributable to the rapid tumor regression in the gastrointestinal tract. Non-operative management should be attempted if possible.
    UNASSIGNED: Oncologists should be aware of the risk of gastrointestinal perforation when initiating cytotoxic chemotherapy on patients with metastatic NSCLC. A multidisciplinary approach is critical in appropriately individualizing care in this patient population.
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  • 文章类型: Journal Article
    未经批准:复发性非小细胞肺癌(NSCLC)的最佳治疗方法尚未标准化。在这项前瞻性队列研究中,我们评估了复发NSCLC治疗后的复发生存率(PRS),并确定了复发后的预后因素.
    未经评估:这项多中心前瞻性队列研究在14家医院进行。本研究的纳入标准为NSCLC根治术后复发的患者。有关复发时患者特征的信息,肿瘤相关变量,初级手术,并收集复发的治疗方法。注册后,后续数据,如治疗和生存结果,每3个月获得一次。
    UNASISIGNED:从2010年到2015年,共纳入505例,并对495例病例进行分析。作为复发的初始治疗,263例患者(53%)接受化疗,46人(9%)接受放化疗,98(20%)接受了确定性放疗,14人(3%)接受姑息性放疗,31例(6%)接受手术切除。其余43名患者(9%)接受支持治疗。所有病例的中位PRS和5年生存率分别为30个月和31.9%,分别。根据初始治疗的中位数PRS如下:支持性治疗,8个月;姑息性放疗,16个月;确定性放疗,30个月;化疗,31个月;放化疗,35个月;和手术,没有到达。多变量分析表明,年龄,性别,性能状态,组织学上存在症状,从初次手术到复发的持续时间,复发灶数量是PRS的独立预后因素。
    UNASSIGNED:复发NSCLC患者的PRS因患者的背景特征和复发的初始治疗而异。
    UNASSIGNED: The optimal treatment for recurrent non-small cell lung cancer (NSCLC) has not been standardized. In this prospective cohort study, we evaluated post-recurrence survival (PRS) after treatment of recurrent NSCLC and identified prognostic factors after recurrence.
    UNASSIGNED: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data, such as treatment and survival outcomes, were obtained every 3 months.
    UNASSIGNED: From 2010 to 2015, 505 cases were enrolled, and 495 cases were analyzed. As initial treatment for recurrence, 263 patients (53%) received chemotherapy, 46 (9%) received chemoradiotherapy, 98 (20%) had definitive radiotherapy, 14 (3%) received palliative radiotherapy, and 31 (6%) underwent surgical resection. The remaining 43 patients (9%) received supportive care. The median PRS and 5-year survival rates for all cases were 30 months and 31.9%, respectively. The median PRS according to the initial treatment was as follows: supportive care, 8 months; palliative radiotherapy, 16 months; definitive radiotherapy, 30 months; chemotherapy, 31 months; chemoradiotherapy, 35 months; and surgery, not reached. A multivariate analysis showed that the age, gender, performance status, histology presence of symptoms, duration from primary surgery to recurrence, and number of recurrent foci were independent prognostic factors for PRS.
    UNASSIGNED: The PRS of patients with recurrent NSCLC was different depending on the patient\'s background characteristics and initial treatment for recurrence.
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  • 文章类型: Journal Article
    大多数疾病涉及细胞的多个生物过程之间复杂的相互作用,组织,器官,和系统水平。基于单一或少数分析物测量的临床测试和生物标志物可能无法捕获患者疾病的复杂性。从容易获得的样品中全面评估生物过程的新方法可能有助于监测,治疗,对许多条件的理解。
    我们提出了一种从血清样品的质谱分析中创建与特定生物过程相关的分数的方法。
    通过以下方式创建感兴趣的过程的得分:(i)使用集合富集分析方法识别与该过程相关的质谱特征,和(ii)使用基于主成分分析的方法将这些特征组合为分数。我们使用非小细胞肺癌患者的队列研究评分的创建,黑色素瘤,和卵巢癌。由于循环蛋白质组适合于免疫反应的研究,它们在癌症的发展和进展中起着至关重要的作用,我们关注与宿主对疾病的反应相关的功能。
    我们证明了生成分数的可行性,它们的再现性,以及它们与临床结果的关联。一旦分数被构建,从循环蛋白质组中评估多种生物学功能仅需要3µL血清。
    这些基于质谱的评分可用于未来的多变量生物标志物或测试开发研究,以告知治疗,疾病监测和提高对多种疾病环境中各种生物功能作用的理解。
    UNASSIGNED: Most diseases involve a complex interplay between multiple biological processes at the cellular, tissue, organ, and systemic levels. Clinical tests and biomarkers based on the measurement of a single or few analytes may not be able to capture the complexity of a patient\'s disease. Novel approaches for comprehensively assessing biological processes from easily obtained samples could help in the monitoring, treatment, and understanding of many conditions.
    UNASSIGNED: We propose a method of creating scores associated with specific biological processes from mass spectral analysis of serum samples.
    UNASSIGNED: A score for a process of interest is created by: (i) identifying mass spectral features associated with the process using set enrichment analysis methods, and (ii) combining these features into a score using a principal component analysis-based approach. We investigate the creation of scores using cohorts of patients with non-small cell lung cancer, melanoma, and ovarian cancer. Since the circulating proteome is amenable to the study of immune responses, which play a critical role in cancer development and progression, we focus on functions related to the host response to disease.
    UNASSIGNED: We demonstrate the feasibility of generating scores, their reproducibility, and their associations with clinical outcomes. Once the scores are constructed, only 3 µL of serum is required for the assessment of multiple biological functions from the circulating proteome.
    UNASSIGNED: These mass spectrometry-based scores could be useful for future multivariate biomarker or test development studies for informing treatment, disease monitoring and improving understanding of the roles of various biological functions in multiple disease settings.
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  • 文章类型: Journal Article
    UNASSIGNED: This retrospective study investigated prognostic factors in advanced non-small cell lung cancer (NSCLC) with bone-only metastasis, and developed a graded prognostic assessment (GPA) model to estimate patient survival.
    UNASSIGNED: The primary endpoint was overall survival. We investigated the patients with advanced NSCLC with bone-only metastasis at the initial diagnosis and diagnosed between 2013 and 2019 in our hospital. A log-rank test and Cox proportional hazards model were used to examine factors. A GPA model was developed in the training set based on the factors that were determined significant according to their hazard ratios and verified by the validation set.
    UNASSIGNED: We finally included 220 patients for analysis. These patients were divided into two groups, 147 cases for the training cohort and 73 for the validation cohort. The following were significant independent prognostic factors, and were included in the GPA model: smoking; EGFR (epidermal growth factor receptor) sensitive/ALK (anaplastic lymphoma kinase) mutations; loss of weight; hypoalbuminemia; and primary site treated by surgery or radiotherapy. GPA score of nil was assigned to smoking, without sensitive mutations, loss of weight, hypoalbuminemia, and without local treatment of primary site; the corresponding superior alternatives were scored 1.5, 2.0, 1.5, 1.5, and 1.5, respectively. The median survival times of patients with GPA scores of nil to 3.0, 3.5 to 6.0, and 6.5 to 8.0 were 14.2, 29.5, and 56.6 months in the training set (P < 0.001) and 15.2, 31.2, and 54.0 months in the validation set (P < 0.001).
    UNASSIGNED: The survival time of patients with NSCLC with bone-only metastasis was dramatically influenced by the presence of the determined prognostic factors. The GPA model developed in this study may be a useful clinical tool to estimate the life expectancy of these patients, and guide treatment.
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  • 文章类型: Case Reports
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  • 文章类型: Journal Article
    Drug repurposing has become a widely used strategy to accelerate the process of finding treatments. While classical de novo drug development involves high costs, risks, and time-consuming paths, drug repurposing allows to reuse already-existing and approved drugs for new indications. Numerous research has been carried out in this field, both in vitro and in silico. Computational drug repurposing methods make use of modern heterogeneous biomedical data to identify and prioritize new indications for old drugs. In the current paper, we present a new complete methodology to evaluate new potentially repurposable drugs based on disease-gene and disease-phenotype associations, identifying significant differences between repurposing and non-repurposing data. We have collected a set of known successful drug repurposing case studies from the literature and we have analysed their dissimilarities with other biomedical data not necessarily participating in repurposing processes. The information used has been obtained from the DISNET platform. We have performed three analyses (at the genetical, phenotypical, and categorization levels), to conclude that there is a statistically significant difference between actual repurposing-related information and non-repurposing data. The insights obtained could be relevant when suggesting new potential drug repurposing hypotheses.
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  • 文章类型: Case Reports
    免疫检查点抑制剂(ICIs)在临床上用于治疗晚期肺癌,在临床试验中,一些患者使用ICI治疗已达到完全缓解(CR)。然而,总结此类患者临床病程的报告有限.我们报告了两例肺腺癌,其中一线pembrolizumab单药治疗达到CR,治疗完成后维持治疗效果。特定患者可以达到CR,即使是那些不符合先前报道的治疗反应预测因子的人,除了高程序性死亡-配体1表达。因此,可以准确预测ICIs临床疗效的生物标志物是必要的.
    Immune checkpoint inhibitors (ICIs) are clinically used for treating advanced lung cancer, and some patients have achieved complete remission (CR) with ICI therapy in clinical trials. However, reports summarizing the clinical courses of such patients are limited. We report two cases of lung adenocarcinoma in which CR was achieved with first-line pembrolizumab monotherapy, and the therapeutic effect was maintained after treatment completion. Specific patients can achieve CR, even those who do not meet the previously reported predictors of treatment response other than high programmed death-ligand 1 expression. Thus, biomarkers that can accurately predict the clinical efficacy of ICIs are warranted.
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