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111.
The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90?mg of brigatinib for 7?days and then 180?mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.  相似文献   
112.
Fibroblast growth factor receptor (FGFR) inhibitors like ponatinib and nintedanib are clinically approved for defined cancer patient cohorts but often exert dose-limiting adverse effects. Hence, we encapsulated the FGFR inhibitors ponatinib, PD173074, and nintedanib into polylactic acid nanoparticles and liposomes to enable increased tumor accumulation/specificity and reduce side effects. Different methods of drug loading were tested and the resulting formulations compared regarding average size distribution as well as encapsulation efficiency. Appropriate encapsulation levels were achieved for liposomal preparations only. Nanoencapsulation resulted in significantly decelerated uptake kinetics in vitro with clearly decreased short-term (up to 72?h) cytotoxicity at higher concentrations. However, in long-term clonogenic assays liposomal formations were equally or even more active as compared to the free drugs. Accordingly, in an FGFR inhibitor-sensitive murine osteosarcoma transplantation model (K7M2), only liposomal but not free ponatinib resulted in significant tumor growth inhibition (by 60.4%) at markedly reduced side effects.  相似文献   
113.
Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used as the first-line treatment for advanced NSCLC; however, the efficacy of drug delivery remains unknown. Hence, we successfully developed erlotinib-conjugated iron oxide nanoparticles (FeDC-E NPs) as theranostic probe that can potentially provide a new avenue for monitoring drug delivering through noninvasive magnetic resonance imaging. MRI ΔR2* relaxivity measurements offer an opportunity to quantitatively evaluate the uptake of FeDC-E NPs at cellular and tumoral levels. Additionally, NF-κB reporter gene system provides NF-κB activation status monitoring to validate the therapeutic efficiency of FeDC-E NPs. FeDC-E NPs not only inhibit the tumor growth and NF-κB-modulated antiapoptotic mechanism but also trigger extrinsic and intrinsic apoptotic pathways. Taken together, dual functional FeDC-E NPs offer diagnostic and therapeutic benefits against lung cancers, indicating that our presented probe could be applied in clinical.  相似文献   
114.

Purpose

Lung cancer is a multifactorial malignancy for which some risk factors, such as chronic lung diseases, their interactions with smoking, and how they differ by race and sex, are not fully understood. We investigated the associations between chronic inflammatory lung disease and non–small cell lung carcinoma (NSCLC) and how sex and race may affect such associations.

Methods

Using logistic regression, we analyzed 1660 lung cancer cases and 1959 population controls and estimated adjusted odds ratios (AORs) and 95% confidence intervals (CIs).

Results

Chronic lung disease was significantly associated with higher odds of having NSCLC in never (AOR = 1.99; 95% CI = 1.19–3.34), former (AOR = 1.68; 95% CI = 1.29–2.20), and current smokers (AOR = 2.40; 95% CI = 1.62–3.57), after adjustment for relevant covariates. For each 5-year increment in chronic lung disease duration, the risk of lung cancer increased only among females (AOR = 1.07; 95% CI = 1.02–1.13). Females, but not males, with asthma were at risk for NSCLC (AOR = 2.08; 95% CI = 1.40–3.10).

Conclusions

This study provides support for chronic lung inflammation as a potential contributing factor to lung cancer risk and possible sex difference in the inflammatory events underlying disease mechanisms.  相似文献   
115.
目的 探讨吉非替尼与重组人血管内皮抑制素注射液联合治疗非小细胞肺癌的临床疗效及安全性。方法 以河南省直第三人民医院2012年1月—2014年1月58例非小细胞肺癌化疗患者为研究对象,根据入院单双号将入选者随机分为对照组和研究组,每组29例,对照组患者单用吉非替尼治疗,研究组患者在此基础上联合重组人血管内皮抑制素注射液治疗,21 d为1个疗程,共进行4个疗程。比较两组患者的临床疗效、各肿瘤标志物水平变化、不良反应发生率及预后情况。结果 研究组及对照组患者客观缓解率(ORR)分别为86.21%、55.17%,两组比较存在显著性差异(P<0.05)。治疗前两组患者各肿瘤标志物水平比较无显著性差异,治疗后两组患者各肿瘤标志物水平均显著降低,前后比较存在显著性差异(P<0.05);治疗后研究组患者各肿瘤标志物水平降低程度显著优于对照组,两组比较存在显著性差异(P<0.05)。随访3年后,研究组患者的生存率、中位生存期及中位无进展生存期均显著高于对照组,两组比较存在显著差异性(P<0.05),两组不良反应的发生率比较无显著性差异。结论 吉非替尼与重组人血管内皮抑制素注射液联合应用可有效提高临床疗效,延长生存期,降低各肿瘤标志物水平,且不增加不良反应,安全性较高,值得在非小细胞肺癌的治疗中进行推广。  相似文献   
116.
目的:比较埃克替尼与吉非替尼治疗既往化疗失败的局部晚期或转移性非小细胞肺癌(NSCLC)患者的近期疗效及不良反应情况。方法:通过Medline、Embase、Cochrane图书馆、中国生物医学文献数据库、中国期刊全文数据库、中文生物医学期刊文献数据库和数字化期刊全文数据库等全面检索国内外相关文献,纳入埃克替尼和吉非替尼治疗既往化疗失败的局部晚期或转移性NSCLC的随机对照试验(RCTs),并对文献进行筛选、评价与分析。采用RevMan 4.2软件对入选研究的近期疗效及不良反应进行Meta分析。结果:共纳入符合标准的RCTs 2项,涉及423例病例。系统评价显示,异质性检验结果良好,可用固定效应模型进行分析。埃克替尼组与吉非替尼组比较,4周疾病控制率、半年总生存率、1年总生存率均无明显差异;埃克替尼组的28周疾病控制率优于吉非替尼组(P=0.01);埃克替尼组与吉非替尼组的皮疹、腹泻、咯血发生率均无显著差异,但埃克替尼治疗组的总不良反应发生率显著低于吉非替尼(P<0.000 01)。结论:对于既往化疗失败的局部晚期或转移性NSCLC,埃克替尼的疗效与吉非替尼相当,且总的耐受性优于吉非替尼。  相似文献   
117.
While PI3K/AKT/mTOR pathway is altered in a variety of cancers including non small cell lung cancer, abnormalities in this pathway are more common in squamous cell lung carcinoma than in adenocarcinoma of the lung. Moreover, aberrant activation of PI3K/AKT/mTOR pathway is one of the mechanisms of acquired resistance to EGFR-TK inhibitors in patients with adenocarcinoma carrying EGFR activating mutations.  相似文献   
118.
张智琪  徐风华  郭荣荣 《中国药房》2014,(34):3226-3229
目的:以生存期和肿瘤进展情况评价吉非替尼治疗晚期非小细胞肺癌(NSCLC)的疗效。方法:回顾性分析2005年6月-2008年12月我院NSCLC期出院患者中服用吉非替尼(吉非替尼组)以及未服用吉非替尼(非吉非替尼组)患者的临床资料。评价33例吉非替尼组患者和38例非吉非替尼组患者的半年生存率、1年生存率、生存期、中位生存期,入组的病例均做了电话随访。调查有肿瘤进展情况评价的44例吉非替尼组患者以及53例非吉非替尼组患者,分别为有疗效评价的吉非替尼组的男性、女性、吸烟、不吸烟、腺癌、非腺癌患者与非吉非替尼组患者进行配对分析。结果:吉非替尼组的半年生存率为78.8%(26/33),1年生存率为36.4%(12/33),生存期为1Ⅳ期出院患者中服用吉非替尼(吉非替尼组)以及未服用吉非替尼(非吉非替尼组)患者的临床资料。评价33例吉非替尼组患者和38例非吉非替尼组患者的半年生存率、1年生存率、生存期、中位生存期,入组的病例均做了电话随访。调查有肿瘤进展情况评价的44例吉非替尼组患者以及53例非吉非替尼组患者,分别为有疗效评价的吉非替尼组的男性、女性、吸烟、不吸烟、腺癌、非腺癌患者与非吉非替尼组患者进行配对分析。结果:吉非替尼组的半年生存率为78.8%(26/33),1年生存率为36.4%(12/33),生存期为122个月;非吉非替尼组的半年生存率为89.5%(34/38),1年生存率为73.7%(28/38),生存期为122个月;非吉非替尼组的半年生存率为89.5%(34/38),1年生存率为73.7%(28/38),生存期为148个月。非吉非替尼组各亚组的中位生存期均高于吉非替尼组,疾病类型亚组差异有统计学意义,性别及吸烟状态两个亚组差异均无统计学意义。性别、吸烟状态和疾病类型各亚组的半年生存率差异均无统计学意义;女性、非腺癌两个亚组的1年生存率差异无统计学意义,其余各亚组的1年生存率差异均有统计学意义。不吸烟亚组的有效控制率差异有统计学意义,其余各亚组的有效控制率差异均无统计学意义。吉非替尼组与非吉非替尼组各亚组的配对分析差异均无统计学意义。结论:NSCLC患者在服用吉非替尼之后半年生存率、1年生存率、中位生存期、有效控制率低于未服用吉非替尼的患者。  相似文献   
119.
It was commonly assumed in the past that blood-brain barrier could efficiently prohibit penetration of large peptide molecules, such as monoclonal antibodies, including programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. This belief has been recently revised by studies that demonstrate the presence of functional lymphatic vessels lining the dural sinuses. Furthermore, the activated circulating T cells have been shown to cross the blood-brain barrier. Such observations created strong rationale for attempts of immunotherapy for patients with brain metastases, used either alone or in combination with radiotherapy. The expected benefit from immunotherapy particularly refers to patients without targetable “driver” mutations who are not considered as candidates for novel targeted therapies. Current inference on efficacy and safety of combination of immunotherapy and radiotherapy in the treatment of brain metastases from non-small cell lung cancer (NSCLC) origins, in most, from the retrospective studies. The existing data suggest that use of immune checkpoint inhibitors (ICIs) with brain radiotherapy improves patients outcome, compared to brain radiotherapy alone. The available data also suggest that concurrent use of ICI and stereotactic radiation therapy (SRT) for brain metastases from NSCLC is tolerable and appears more effective than sequential combination of radiotherapy and ICI. Use of steroids appeared detrimental. Since a dependence between the risk of adverse events and type of ICI therapy as well as tumor pathology was found, further studies are required to establish optimal dosage, selection of drugs and sequence of ICI and brain radiotherapy in patients with brain metastases from NSCLC.  相似文献   
120.
BackgroundRobot assisted thoracic surgery (RATS) is the minimally invasive surgical technique of choice for treatment of patients with non-small cell lung cancer (NSCLC), at the Isala Hospital. The aim of this study is to compare clinical and pathological staging results and mediastinal recurrence after RATS for anatomical resections of lung cancer as surrogate markers for quality of mediastinal lymph node dissection (MLND).MethodsThis single institute retrospective study was conducted in patients who underwent RATS for NSCLC. Excluded were patients with a history of concurrent malignant disease, with other previous neoplasms, with small cell lung cancer (SCLC) and patients in whom the robotic technique was converted to thoracotomy, prior to lymph node dissection. Data were obtained from the hospital database. The difference between clinical and pathological staging was expressed as upstaging and downstaging. Computed Tomography scanning was used for follow-up, and diagnosis of mediastinal recurrence.ResultsFrom November 2011 to May 2016, 227 patients underwent RATS at Isala Hospital Zwolle, the Netherlands. Of those, 130 (mean age, 69.5±9.3 years) met the eligibility criteria. Preoperative mediastinal lymph node staging was done by endoscopic ultrasound/endobronchial ultrasound, by positron emission tomography (PET) or mediastinoscopy. In 14 patients (10.8%) unforeseen N2 disease was found, 6 patients (4.6%) were upstaged from cN0 to pN2 and 8 patients (6.2%) were upstaged from cN1 to pN2. Mediastinal recurrence was detected in 7 patients (5.4%) during a median follow-up of 54 months (range, 1.5–102 months).ConclusionsIn patients with NSCLC, who underwent anatomical resection by means of RATS, an unforeseen N2 disease rate of 10.8% was demonstrated and a mediastinal recurrence rate of 5.4%. It is concluded that robotic surgery provides an accurate lymph node dissection.  相似文献   
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