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Effectiveness and safety of combined nimotuzumab and S-1 chemotherapy with concurrent radiotherapy for locally advanced esophageal cancer in malnourished and elderly patients:A prospective phase Ⅱ study

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Chinese Journal of cancer Research 2024年第3期36卷 270-281页

作者： Guojie Feng Jiao Li Nuo Yu Ziyu Zheng Xiongtao Yang Lei Deng Tao Zhang Wenqing Wang Wenyang Liu Jianyang Wang Qinfu Feng Jima Lyu Zefen Xiao Zongmei Zhou Nan Bi Jianjun Qin Xin Wang department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

Objective: Definitive chemoradiotherapy(dCRT) is the standard treatment for unresectable locally advanced esophageal cancer. However, this treatment is associated with substantial toxicity, and most malnourished or elderly patients are unable to complete this therapy. Therefore, there is a need for a more suitable radiotherapy combination regimen for this population. This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002(NRS-2002) score.Methods: Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled. They were treated with S-1 and nimotuzumab with concurrent radiotherapy, followed by surgery or definitive radiotherapy. The primary endpoint was the locoregional control(LRC) rate.Results: A total of 55 patients who met the study criteria were enrolled. After completion of treatment, surgery was performed in 15 patients and radiotherapy was continued in 40 patients. The median follow-up period was 33.3[95% confidence interval(95% CI), 31.4-35.1)] months. The LRC rate was 77.2%(95% CI, 66.6%-89.4%) at 1 year in the entire population. The overall survival(OS) rate and event-free survival(EFS) rate were 57.5% and 51.5% at 3 years, respectively. Surgery was associated with better LRC [hazard ratio(HR)=0.16; 95% CI,0.04-0.70; P=0.015], OS(HR=0.19; 95% CI, 0.04-0.80; P=0.024), and EFS(HR=0.25; 95% CI, 0.08-0.75;P=0.013). Most adverse events were of grade 1 or 2, and no severe adverse events occurred.Conclusions: For malnourished or elderly patients with locally advanced esophageal cancer, radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.

关键词： Esophageal carcinoma squamous cell carcinoma nutritional risk score nimotuzumab S-1 definitive chemoradiotherapy

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A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

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Chinese Journal of cancer Research 2024年第1期36卷 46-54页

作者： Pin Zhang Lin Wang Yueying Zhen Zhihong Wang Hesheng Zhang Richard Jones Binghe Xu department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Tianjin Hemay Pharmaceutical Co. LTDTianjin 300308China

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

关键词： Advanced breast cancer HER2-positive Hemay022 first-in-human trial

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Mesenchymal-epithelial transition factor amplification correlates with adverse pathological features and poor clinical outcome in colorectal cancer

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1395-1406页

作者： Qiu-Xiao Yu Ping-Ying Fu Chi Zhang Li Li Wen-Ting Huang department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518116Guangdong ProvinceChina

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and the second most common cause of cancer-related mortality worldwide.Mesenchymal-epithelial transition factor(MET)gene participates in multiple tumor biology and shows clinical potential for pharmacological manipulation in tumor treatment.MET amplification has been reported in CRC,but data are very limited.Investigating pathological values of MET in CRC may provide new therapeutic and genetic screening options in future clinical practice.AIM To determine the pathological significance of MET amplification in CRC and to propose a feasible screening strategy.METHODS A number of 205 newly diagnosed CRC patients undergoing surgical resection without any preoperative therapy at Shenzhen cancer Hospital of Chinese Academy of Medical Sciences were recruited.All patients were without RAS/RAF mutation or microsatellite instability-high.MET amplification and c-MET protein expression were analyzed using fluorescence in situ hybridization(FISH)and immunohistochemistry(IHC),respectively.Correlations between MET aberration and pathological features were detected using the chi-squared test.Progression free survival(PFS)during the two-year follow-up was detected using the Kaplan-Meier method and log rank test.The results of MET FISH and IHC were com pared using one-way ANOVA.RESULTS Polysomy-induced MET amplification was observed in 14.4%of cases,and focal MET amplification was not detected.Polysomy-induced MET amplification was associated with a higher frequency of lymph node metastasis(LNM)(P<0.001)and higher tumor budding grade(P=0.02).In the survival analysis,significant difference was detected between patients with amplified-and non-amplified MET in a two-year follow-up after the first diagnosis(P=0.001).C-MET scores of 0,1+,2+,and 3+were observed in 1.4%,24.9%,54.7%,and 19.0%of tumors,respectively.C-MET overexpression correlated with higher frequency of LNM(P=0.002),but no significant difference of PFS was detected between patients with different protein lev

关键词： Colorectal cancer MET Amplification Pathological features Prognosis Fluorescence in situ hybridization

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Invasive ant learning is not affected by seven potential neuroactive chemicals

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Current Zoology 2024年第1期70卷 87-97页

作者： Henrique Galante Tomer J.Czaczkes department of Zoology and Evolutionary biology Animal Comparative Economics LaboratoryUniversity of Regensburg93053 Regensburg Germany

Argentine ants Linepithema humile are one of the most damaging invasive alien species worldwide.Enhancing or disrupting cognitive abilities,such as learning,has the potential to improve management efforts,for example by increasing preference for a bait,or improving ants'ability to learn its characteristics or location.Nectar-feeding insects are often the victims of psychoactive manipulation,with plants lacing their nectar with secondary metabolites such as alkaloids and non-protein amino acids which often alter learning,foraging,or recruitment.However,the effect of neuroactive chemicals has seldomly been explored in ants.Here,we test the effects of seven potential neuroactive chemicals-two alkaloids:caffeine and nicotine;two biogenic amines:dopamine and octopamine,and three nonprotein amino acids:β-alanine,GABA and taurineon the cognitive abilities of invasive L.humile using bifurcation mazes.Our results confirm that these ants are strong associative learners,requiring as little as one experience to develop an association.However,we show no short-term effect of any of the chemicals tested on spatial learning,and in addition no effect of caffeine on short-term olfactory learning.This lack of effect is surprising,given the extensive reports of the tested chemicals affecting learning and foraging in bees.This mismatch could be due to the heavy bias towards bees in the literature,a positive result publicationbias,ordifferences inmethodology.

关键词： associativelearning caffeine memory neuroactivechemicals

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A comparative study for petroleum removal capacities of the bacterial consortia entrapped in sodium alginate,sodium alginate/poly(vinyl alcohol),and bushnell haas agar

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Petroleum Science 2024年第1期21卷 705-715页

作者： Sezen Bilen Ozyurek department of biology(Biotechnology) Faculty of ScienceHacettepe UniversityAnkaraBeytepe06800Turkey

The purpose of this study was to identify and compare the degradation efficiencies of free and entrapped bacterial consortia(Staphylococcus capitis CP053957.1 and Achromobacter marplatensis MT078618.1)to different polymers such as Sodium Alginate(SA),Sodium Alginate/Poly(Vinyl Alcohol)(SA/PVA),and Bushnell Haas Agar(BHA).In addition to SA and SA/PVA,which are cost-effective,non-toxic and have different functional groups,BHA,which is frequently encountered in laboratory-scale studies but has not been used as an entrapment material until now.Based on these,the polymers with different surface morphologies and chemical compositions were analyzed by SEM and FT-IR.While the petroleum removal efficiency was higher with the entrapped bacterial consortia than with the free one,BHA-entrapped bacterial consortium enhanced the petroleum removal more than SA and SA/PVA.Accordingly,the degradation rate of bacterial consortia entrapped with BHA was 2.039 day^(-1),SA/PVA was 1.560,SA was 0.993,the half-life period of BHA-entrapped bacterial consortia is quite low(t_(1/2)=0.339)compared with SA(t_(1/2)=0.444)and SA/PVA(t_(1/2)=0.697).The effects of the four main factors such as:amount of BHA(0.5,1,1.5,2,2.5,3 g),disc size(4,5,6,7,8 mm),inoculum concentration(1,2.5,5,7.5,10 mL),and incubation period on petroleum removal were also investigated.The maximum petroleum removal(94.5%)was obtained at≥2.5 mL of bacterial consortium entrapped in 2 g BHA with a 7 mm disc size at 168 h and the results were also confirmed by statistical analysis.Although a decrease was observed during the reuse of bacterial consortium entrapped in BHA,the petroleum removal was still above 50%at 10th cycle.Based on GC-MS analysis,the removal capacity of BHA-entrapped consortium was over 90%for short-chain n-alkanes and 80%for medium-chain n-alkanes.Overall,the obtained data are expected to provide a potential guideline in cleaning up the large-scale oil pollution in the future.Since there has been no similar study investigating petroleum removal with the bacte

关键词： Entrapment of bacterial consortia Petroleum RemovalBushnell Haas agar Sodium alginate Sodium alginate/poly(vinyl alcohol)

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