Continuous intravenous infusion of recombinant human endostatin using infusion pump plus chemotherapy in non-small cell lung cancer

BACKGROUND Lung cancer is one of the deadliest cancers in the world with the highest incidence and mortality rate among all cancers.Non-small cell lung cancer(NSCLC)accounts for approximately 80%of primary lung cancer.However,efficacy and safety of the current regimens for NSCLC is unsatisfactory.Therefore,there has been an increasing urgency for development of potential therapeutic therapies for NSCLC.AIM To investigate the therapeutic outcomes and safety of continuous intravenous infusion of recombinant human endostatin(Rh-endostain)using an infusion pump in retreated advanced NSCLC.METHODS Patients with retreated advanced NSCLC who were admitted to Zhejiang Provincial People's Hospital from October 2017 to April 2019 were recruited.These patients received continuous intravenous infusion of Rh-endostain using an infusion pump.Objective response rate(ORR),clinical benefit rate(CBR),median progression-free survival(mPFS),and incidences of adverse events(AEs)were analyzed after treatment.RESULTS A total of 45 patients with retreated advanced NSCLC were included,and all of them were evaluated.In these patients,ORR was 22.2%,CBR was 84.4%,and mPFS was 5.3 mo.The following AEs were observed,decreased hemoglobin(34 cases,75.6%),nausea/vomiting(32 cases,71.1%),elevated transaminase(24 cases,53.3%),leukopenia(16 cases,35.6%),thrombocytopenia(14 cases,31.1%),and constipation(1 case,3.4%).None of the patients had leukopenia,nausea/vomiting,and constipation of grade III and above.CONCLUSION The patients showed improved adherence to 5-d continuous intravenous infusion of Rh-endostain using an infusion pump.Favorable efficacy and safety of this treatment regimen were achieved in retreated advanced NSCLC.

HER3-targeted therapeutic antibodies and antibody-drug conjugates in non-small cell lung cancer refractory to EGFR-tyrosine kinase inhibitors

Human epidermal growth factor receptor 3(HER3)is a unique member of the human epidermal growth factor receptor(HER/EGFR)family,since it has negligible kinase activity.Therefore,HER3 must interact with a kinase-proficient receptor to form a heterodimer,leading to the activation of signaling cascades.Overexpression of HER3 is observed in various human cancers,including non-small cell lung cancer(NSCLC),and correlates with poor clinical outcomes in patients.Studies on the underlying mechanism demonstrate that HER3-initiated signaling promotes tumor metastasis and causes treatment failure in human cancers.Upregulation of HER3 is frequently observed in EGFR-mutant NSCLC treated with EGFR-tyrosine kinase inhibitors(TKIs).Increased expression of HER3 triggers the so-called EGFR-independent mechanism via interactions with other receptors to activate“by-pass signaling pathways”,thereby resulting in resistance to EGFR-TKIs.To date,no HER3-targeted therapy has been approved for cancer treatment.In both preclinical and clinical studies,targeting HER3 with a blocking an-tibody(Ab)is the only strategy being examined.Recent evaluations of an anti-HER3 Ab-drug conjugate(ADC)show promising results in patients with EGFR-TKI-resistant NSCLC.Herein,we summarize our understanding of the unique biology of HER3 in NSCLC refractory to EGFR-TKIs,with a focus on its dimerization partners and subsequent activation of signaling pathways.We also discuss the latest development of the therapeutic Abs and ADCs targeting HER3 to abrogate EGFR-TKI resistance in NSCLC.

吉西他滨对人非小细胞肺癌HCC827活性和凋亡的影响

目的：研究吉西他滨对人非小细胞肺癌HCC827细胞活性以及凋亡的影响,以及与Bcl-2表达的关系。方法：采用cell counting kit-8法、细胞核Hochest33258染色法、流式细胞仪Annexin V-FITC/PI双染法等多种方法,体外研究吉西他滨对人非小细胞肺癌HCC827的活性、凋亡和细胞周期的影响;采用Western blot法,观察药物作用后细胞中Bcl-2蛋白表达的变化。结果：吉西他滨（0.1～1 000 ng/ml）对人非小细胞肺癌HCC827活性具有抑制作用,并有促凋亡效应。此外,可以将细胞阻滞在S期。在吉西他滨诱导的细胞凋亡过程中,凋亡因子Bcl-2蛋白的表达下调。结论：吉西他滨可以抑制人非小细胞肺癌HCC827细胞的增殖,并诱导细胞凋亡,S期周期阻滞,其诱导的凋亡可能是其杀死肿瘤细胞的主要机制之一,此外,凋亡与相关基因Bcl-2蛋白的表达具有一定关系。

Synergistic Cytotoxicity of Ampelopsin Sodium and Carboplatin in Human Non-Small Cell Lung Cancer Cell Line SPC-A1 by G1 Cell Cycle Arrested

Objective： To evaluate the cytotoxic effects of ampelopsin sodium（Amp-Na） and carboplatin（CBP） used alone or in combination on human non-small cell lung cancer（NSCLC） cells SPC-A1 in vitro and its related mechanism. Methods： Cytotoxic effects were assessed by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） assays. The synergistic effects of the drugs were calculated with coefficient of drug interaction（CDI）. Cell cycle was determined by flow cytometry（FCM）. The levels of p53, p21, cyclin E, cyclin D1, and phosphorylated cyclin-dependent kinase-2（p-CDK2） were evaluated by Western blot. Results： Amp-Na（6.25–200 μg/m L） and CBP（3.13–100 μg/m L） alone exhibited prominent cytotoxic activity in a concentration-dependent manner on SPC-A1 cells with 50% inhibitive concentration values of 57.07±14.46 and 34.97±6.30 μg/m L, respectively. Drug combinations were associated with significantly higher cytotoxic effects than each drug alone（P〈0.05 or 0.01）. The CDI analysis confirmed the synergy of Amp-Na and CBP on inhibiting cancer cell viability across a wide concentration range（CDI 〈1）. FCM and Western blot showed that synergistic cytotoxic effects of Amp-Na and CBP were related to G1 arrested which mainly mediated by p21 through the inhibition of CDK2 activity independent of the p53 tumor suppressor pathway. Conclusions： AmpNa exhibits anticancer activities and enhances the antitumor activities of CBP through up-regulation of p21 and inhibition of CDK2 activity in human NSCLC cells SPC-A1. These results suggest that Amp-Na may be applied to enhance the anticancer action of CBP.

Value of serum NGAL and HE4 content change for diagnosing lung cancer and evaluating disease progression

Objective: To study the value of serum NGAL and HE4 content change for diagnosing non-small cell lung cancer (NSCLC) and evaluating disease progression. Methods: Patients who were diagnosed with NSCLC and underwent surgical resection in the First Affiliated Hospital of Chengdu Medical College between February 2015 and March 2017 were selected as the NSCLC group, and healthy volunteers who received physical examination over the same period were selected as control group. The NGAL and HE4 contents in serum of NSCLC group and control group as well as the expression of proliferation, apoptosis and invasion genes in NSCLC lesion of NSCLC group were detected. Results: Serum NGAL and HE4 levels of NSCLC group were significantly higher than those of control group, serum NGAL and HE4 levels of patients with TNM II and TNM III NSCLC were significantly higher than those of patients with TNM I NSCLC, and serum NGAL and HE4 levels of patients with TNM III NSCLC were significantly higher than those of patients with TNM II NSCLC;c-myc, Survivin, CatL, Vimentin, Slug and Snail mRNA expression in NSCLC lesion were significantly higher than those in adjacent lesion and positively correlated with serum NGAL and HE4 levels while PTEN, LATS1 and E-cadherin mRNA expression were significantly lower than those in adjacent lesion and negatively correlated with serum NGAL and HE4 levels. Conclusion: Abnormally elevated NGAL and HE4 in the serum of NSCLC patients can evaluate the proliferation and invasion of cancer cells to a certain extent.