Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett's esophagus to adenocarcinoma

AIM： To investigate the expression of cyclooxygenase-2 （COX-2） and epithelial growth factor receptor （EGFR） throughout the progression of Barrett＇s esophagus （BE）. METHODS： COX-2 and EGFR protein expressions were detected by using immunohistochemical method. A detailed cytomorphological changes were determined. Areas of COX-2 and EGFR expression were quantified by using computer Imaging System. RESULTS： The expressions of both COX-2 and EGFR increased along with the progression from BE to esophagus adenocarcinoma （EAC）. A positive correlation was found between COX-2 expression and EGFR expression. CONCLUSION： COX-2 and EGFR may be cooperative in the stepwise progression from BE to EAC, thereby leading to carcinogenesis.

EGFR Mutation and FHIT Methylation: Inverse Relationship in Patients with Lung Adenocarcinoma and Tuberculosis

Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:The presence of EGFR mutations and the methylation status of the FHIT gene in patients presenting with AC and TB were analyzed.The correlation between TB status and the observed genetic and epigenetic variations was also examined.Results:Among the 90 patients included in the study,38 exhibited EGFR mutations(14 among those with TB and 24 among those without TB),while 29 exhibited FHIT myelination(19 among those with TB and 10 among those without TB).Furthermore,the protein expression levels of EGFR and FHIT were significantly higher in patients diagnosed solely with AC compared to those presenting with both AC and TB.A robust inverse correlation was identified between TB status and the frequency of EGFR mutation(P<0.001).Moreover,significant associations were observed between TB status and FHIT methylation(P<0.01).Conclusion:The findings suggest a correlation between TB and the prevalence of EGFR mutation and FHIT methylation in the pathogenesis of AC.

A Phase Ⅱ Clinical Trial of Celecoxib Combined with Platinum-Based Regimen as First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer Patients with Cyclooxygenase-2 Positive Expression

Objective： To evaluate the efficacy and safety of celecoxib treatment of advanced non-small cell lung cancer （NSCLC）, and combined therapy by molecular analysis. plus platinum-doublet as first-line chemotherapy in to determine the subgroup benefiting from celecoxib Methods： A total of 44 treatment-naive patients of advanced NSCLC with positive cyclooxygenase-2 （COX-2） expression confirmed by immunohistochemical （IHC） staining were designed to receive celecoxib plus platinum-doublet chemotherapy （cisplatin plus gemcitabine, novelbine or docetaxol） from February 2005 to May 2007. On 5-7 day before chemotherapy, 400 mg celecoxib was administered twice a day orally until obvious evidence of disease progression or intolerable toxicity was found. Adverse events were recorded according to NCI-CTC criteria. The primary endpoint was overall survival （OS）. The secondary endpoints included progression-free survival （PFS）, 1-year survival rate, response rate （RR） and safety. Additionally, we detected epithelial growth factor receptor （EGFR） status including EGFR gene amplification by real-time PCR and gene mutations by DHPLC followed by sequencing. Results： The response rate was 45% （20/44）, and the disease control rate （DCR） was 59% （26/44）. The median progression-free survival time and median survival time were 6 m and 18 m, respectively. The l-year survival rate was 68%. Chemotherapy cycle numbers and best response were found to be the predictive factors for PFS by COX model analysis （P=0.023 and P=0.000, respectively）. No factor was found to affect OS. The most common toxicities included neutropenia and nausea/vomit. EGFR gene amplification was an independent prognostic factor influencing OS （P=0.0002）. Patients with EGFR mutations （exon 21） had a tendency of disease progression （P=0.041）. Conclusion： Encouraging activities of celecoxib combined with platinum-doublet chemotherapy were demonstrated in treatment-naive patients with advanced NSCLC, with good tolerances. For COX-2 IHC positive patients, positive EGFR amplification and mutation might be related to poor clinical outcomes.

Evaluation of Three Small Molecular Drugs for Targeted Therapy to Treat Nonsmall Cell Lung Cancer

Objective： To guide the optimal selection among first-generation epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） in clinical practice.This review attempted to provide a thorough comparison among three first-generation EGFR-TKIs, namely icotinib,erlotinib, and gefitinib, with regard to their molecular structure, pharmacokinetic parameters, clinical data, adverse reactions, and contraindications.Data Sources： An electronic literature search of the PubMed database and Google Scholar for all the available articles regarding gefitinib,icotinib, and erlotinib in the English language from January 2005 to December 2014 was used.Study Selection： The search terms or keywords included but not limited to ＆quot;lung cancer＆quot;, ＆quot;nonsmall cell lung cancer （NSCLC）＆quot;,＆quot;epidemiology＆quot;, ＆quot;EGFR＆quot;, ＆quot;TKIs＆quot;, and ＆quot;optimal selection＆quot;.Results： As suggested by this review, even though the three first-generation EGFR-TKIs share the quinazoline structure, erlotinib had the strongest apoptosis induction activity because of its use of a different side-chain.The pharmacokinetic parameters indicated that both erlotinib and icotinib are affected by food.The therapeutic window of erlotinib is narrow, and the recommended dosage is close to the maximum tolerable dosage.Icotinib enjoys a wider therapeutic window, and its concentration in the blood is within a safe dosage range even if it is administered with food.Based on multiple large-scale clinical trials, erlotinib is universally applied as the first-line treatment.In marked contrast, icotinib is available only in China as the second-or third-line therapeutic approach for treating advanced lung cancer.In addition, it exhibits a similar efficacy but better safety profile than gefitinib.Conclusions： Although there is a paucity of literature regarding whether icotinib is superior to erlotinib, its superior toxicity profile, noninferior efficacy, and lower cost indicate that it is a better alternative for Chinese patients living with advanced NSCLC.

NIR-II emissive dye based polymer nanoparticle targeting EGFR for oral cancer theranostics

Oral cancer is a common malignant tumor of the head and neck,and surgery combined with radiotherapy and chemotherapy is the primary treatment modality.However,a positive resection margin that may lead to recurrence after surgery has always been a critical issue to address.Furthermore,radiotherapy and chemotherapy also have shortcomings such as resistance to chemotherapy and radiation,lack of targeting,and severe side effects.Therefore,exploring new methods of tumor surgical navigation and tumor treatment is of great significance for oral cancer.Although,the emerging near-infrared II(NIR-II,1,000–1,700 nm)region fluorescent imaging has revolutionized surgical navigation,a high tumor-targeting fluorescent probe remains lacking.Furthermore,while emerging photothermal therapy(PTT)can overcome chemoradiotherapy’s shortcomings and achieve precise treatment of tumors,its clinical application is still limited by the lack of high photothermal conversion efficiency,high photothermal stability,and highly penetrating materials.Herein,a NIR-II dye SQ890 is developed for tumor imaging and PTT of oral cancer.By assembling into nanoparticles(NPs)and being modified with epithelial growth factor receptor(EGFR)-targeting peptides GE11,SQ890 NPs-Pep can specifically accumulate in tumor sites via active targeting,and realize photoacoustic/NIR-II fluorescence dual-modality imaging-guided PTT of oral cancer.