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Predictive and prognostic implications of 4E-BP1, Beclin-1, and LC3for cetuximab treatment combined with chemotherapy in advanced colorectal cancer with wild-type KRAS: Analysis from real-world data

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World Journal of Gastroenterology 2019年第15期25卷 1840-1852页

作者： gui-fang guo Yi-Xing Wang Yi-Jun Zhang Xiu-Xing Chen Jia-Bin Lu Hao-Hua Wang Chang Jiang Hui-Quan Qiu Liang-Ping Xia VIP Department Sun Yat-sen University Cancer Center Collaborative Innovation Center for Cancer Medicine State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center Pathology Department Sun Yat-sen University Cancer Center

BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor(EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting *** To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type *** ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005,to October 1, 2015, were studied. Expression of autophagy-related proteins[Beclin1, microtubule-associated protein 1 A/B-light chain 3(LC3), and 4 Ebinding protein 1(4 E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4 E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were *** In CACO-2 cells exposed to cetuximab, LC3 and 4 E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients,immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3(0.657, P < 0.001) and 4 E-BP1(0.211, P = 0.042) in ACRC ***3 was significantly overexpressed in tumor tissues compared to normal tissues(P < 0.001). In 45 patients with wild-type KRAS, the expression levels of these three pro

关键词： 4E-binding protein 1 Beclin-1 Microtubule-associated protein 1A/B-light chain 3 Advanced colorectal cancer Cetuximab efficacy Prognosis

Initial Progression-Free Survival after Non-First Line TKIs Therapy Potentially guides Immediate Treatment after Its Failure in Advanced Non-Small Cell Lung Cancer

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Clinical oncology and cancer researeh 2012年第1期9卷 38-43页

作者： fang Wang gui-fang guo Hui-juan Qiu Wen-zhuo He Fei-fei Zhou Xu-xian Chen Pi-li Hu Bei Zhang Chen-xi Yin Li Zhang Liang-ping Xia State Key Laboratory of Oncology in South China VIP Region Sun Yat-sen University Cancer Center Tumor Center The Foshan First People's HospitalFoshan 528000China Department of Medical Oncology Sun Yat-sen University Cancer Center

Objective The standard therapy alter failure of the initial non-first line epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TK1） treatment in advanced non-small cell lung cancer （NSCLC） has not yet been established. The aim of the current study was to identify whether the 2nd TKI treatment or chemotherapy （paclitaxel-containing or non-paclitaxel regimen） is the appropriate treatment for patients with NSCLC based on the efficacy of the initial TKls. Methods Seventy-two advanced NSCLC patients who had accepted 2nd TKIs or chemotherapy immediately alter failure of the initial TKIs in non-first line setting from May 1, 2004 to January 31, 2010 at the Sun Yat-sen University Cancer Center were enrolled. The primary endpoint [2nd progression-free survival （PFS）] and the second endpoint loverall survival （OS）] were compared among the 2＇＇d TKI and chemotherapy groups as well as their subgroups. Results （1） Twenty-one patients were treated with 2 TKIs, and 51 patients were administered chemotherapy after failure of the initial non-first line TKI treatment. There was nonsignificant difference in the responses （P=0.900） [2nd PFS （P=0.833） and OS （P=0.369）] between the 2nd TKI and chemotherapy groups. （2） In tile 2nd TKI group, 9 patients exhibited PFS_〉7 months. The initial TKI treatment group exhibited a longer 2＂d PFS than the other 12 patients with an initial PFS〈7 months （7 months vs. 2 months, P=0.019）. However, these groups had nonsignificantly different OS （P=0.369）. （3） In the chemotherapy group, patients with PFS〈5 months exhibited longer 2＇1~ PFS than those with PFS 〉 5 months in the initial TKI treatment （3 months vs. 2 months, P=0.039）. （4） In the chemotherapy group, nd patients treated with paclitaxel-containing regimen showed longer 2 PFS than those treated with non-paclitaxel regimen （, months t,s. 2.3 months, P=0.043）. Conclusions Patients with PFS_〉7 months or 〈5 months under the initial TKI treatment potentially benefit from the 2nd TK1 treatm

关键词： lung neoplasm chemotherapy survival analysis erlotinib

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Pemetrexed Monotherapy and Pemetrexed Plus Platinum Combination Therapy as Non-First-Line Treatments for Advanced Non-Small Cell Lung Cancer

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Clinical oncology and cancer researeh 2011年第4期8卷 235-241页

作者： fang WANG gui-fang guo Hui-juan QIU Xu-xian CHEN Pi-fi HU Fei-fei ZHOU Wen-zhuo HE Bei ZHANG Liang-ping XIA State Key Laboratory of Oncology in SouthChina Guangzhou 510060 GuangdongProvince China VIP Region Sun Yat-sen University CancerCenter Guangzhou 510060 GuangdongProvince China Tumor Center The Foshan First People'sHospital Foshan 510060 GuangdongProvince China

OBJECTIVE Data on the efficacy profiles of pemetrexed mono- therapy and pemetrexed plus platinum combination therapy in the non-first-line setting for patients with advanced non-small cell lung cancer （NSCLC） are limited, and previous studies have reported contradictory results. This study investigated and compared the efficacy and toxicity profiles of these two regimens to provide a broader understanding of their dynamics. METHODS Previously treated patients with advanced and/or recurrent NSCLC who received pemetrexed monotherapy or peme- trexed plus platinum combination therapy between January 1, 2006, and December 31, 2009, at Sun Yat-sen University Cancer Center were evaluated. The primary endpoint of this study was progres- sion-free survival （PFS）, whereas the secondary endpoints were overall response rate （ORR）, disease control rate （DCR）, overall survival （OS）, and toxicity. Survival was analyzed using the Kaplan- Meier method. Univariate analysis was performed to identify the factors potentially influencing OS, and chi-square analysis was carried out to compare ORR and DCR. RESULTS Forty-six patients with advanced and/or recurrent NSCLC were analyzed; of these patients, 25 were given pemetrexed monotherapy and 21 received pemetrexed plus platinum combina- tion therapy. The following correspond to the rates recorded for the pemetrexed monotherapy group and the pemetrexed plus platinum group： median PFS, 1.97 and 2.3 months （P=0.565）; median OS, 30.93 and 30.33 months （P=0.877）; ORR, 8% （2/25） and 9.5% （2/21）（P=0.857）; and DCR, 32% （8/25） and 57.1% （12/21）（P=0.09）. Univariate analysis revealed that no factor was correlated with OS from NSCLC （P〉0.05 for all）. Gastrointestinal toxicity in the pemetrexed plus platinum group was modestly higher than that in the pemetrexed monotherapy group （P=0.034）, but other adverse events were similar between the groups. CONCLUSION Compared with pemetrexed monotherapy, peme- trexed plus platinum combination therapy causes m

关键词： pemetrexed non-small cell lung cancer efficacy safety non-first-line setting.

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World Journal of Gastroenterology 2011年第43期17卷 4779-4786页

作者： gui-fang guo Wen-Qi Jiang Bei Zhang Yu-Chen Cai Rui-Hua Xu Xu-Xian Chen fang Wang Liang-Ping Xia State Key Laboratory of Oncology Cancer Center Sun Yat-Sen University Guangzhou 510060 Guangdong Province China

AIM:To investigate the utility of Beclin-1 and LC3,two autophagy-related proteins,in predicting the cetuximab efficacy in advanced colorectal cancer(ACRC) . METHODS:The data of 85 patients with ACRC treated at the Sun Yat-sen University Cancer Center from March 1,2005 to December 31,2008 were studied,including 45 cases treated with cetuximab-containing chemotherapy and 40 cases treated with non-cetuximab-containing ***-1 and LC3 expression was evaluated by immunohistochemistry,and KRAS status was evaluated by polymerase chain reaction. RESULTS:Beclin-1 and LC3 expression in ACRC wassignificantly correlated(r=0.44,P<0.01);however,LC3 was more highly expressed in cancerous tissues than in normal tissues(Z=-2.63,P<0.01) .In the cetuximab-containing chemotherapy group,patients with low LC3 expression had higher objective response rates(ORRs) than those with high LC3 expression(52.9%vs 17.9%,P=0.01) ,and patients with low Beclin-1 expression had a longer median progressionfree survival(PFS) than their counterparts with higher Beclin-1 expression(9.0 mo vs 3.0 mo,P=0.01) . However,neither of these predictive relationships was detected in the group treated with non-cetuximabcontaining *** with wild-type KRAS had higher ORRs(42.3%vs 9.1%,P=0.049) and disease control rates(DCRs)(73.1%vs 36.4%,P= 0.035) ,and longer median PFS(5.5 mo vs 2.5 mo,P= 0.02) than those with mutant KRAS in the cetuximabcontaining chemotherapy *** Beclin-1(P= 0.52) nor LC3(P=0.32) expression was significantly correlated with KRAS status. CONCLUSION:Patients with low Beclin-1 expression had a longer PFS than those with high Beclin-1 expression,and patients with low LC3 expression had a higher ORR in ACRC patients treated with cetuximab-containing chemotherapy.

关键词： Beclin-1 Cetuximab Colorectal neoplasms Drug therapy LC3

Palliative primary tumor resection provides survival beneits for the patients with metastatic colorectal cancer and low circulating levels of dehydrogenase and carcinoembryonic antigen

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Chinese Journal of Cancer 2016年第9期35卷 468-475页

作者： Wen-Zhuo He Yu-Ming Rong Chang Jiang fang-Xin Liao Chen-Xi Yin gui-fang guo Hui-Juan Qiu Bei Zhang Liang-Ping Xia State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat?sen University Cancer Center VIP Region Sun Yat?sen University Cancer Center

Background: It remains controversial whether palliative primary tumor resection(PPTR) can provide survival benefits to the patients with metastatic colorectal cancer(m CRC) who have unresectable metastases. The aim of this study was to evaluate whether PPTR could improve the survival of patients with m ***: We conducted a retrospective study on consecutive m CRC patients with unresectable metastases who were diagnosed at Sun Yat?sen University Cancer Center in Guangzhou, Guangdong, China, between January 2005 and December 2012. Overall survival(OS) and progression?free survival(PFS) after first?line chemotherapy failure were compared between the PPTR and non?PPTR patient ***: A total of 387 patients were identified, including 254 who underwent PPTR and 133 who did not. The median OS of the PPTR and non?PPTR groups was 20.8 and 14.8 months(P < 0.001), respectively. The median PFS after first?line chemotherapy was 7.3 and 4.8 months(P < 0.001) in the PPTR and non?PPTR groups, respectively. A larger proportion of patients in the PPTR group(219 of 254, 86.2%) showed local progression compared with that of patients in the non?PPTR group(95 of 133, 71.4%; P < 0.001). Only patients with normal lactate dehydrogenase(LDH) levels and with carcinoembryonic antigen(CEA) levels <70 ng/m L benefited from PPTR(median OS, 22.2 months for the PPTR group and 16.2 months for the non?PPTR group; P < 0.001).Conclusions: For m CRC patients with unresectable metastases, PPTR can improve OS and PFS after first?line chemo?therapy and decrease the incidence of new organ involvement. However, PPTR should be recommended only for patients with normal LDH levels and with CEA levels <70 ng/m L.

关键词：乳酸脱氢酶结直肠癌转移性患者肿瘤水福利手术切除

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THE SPECTRAL RADIUS OF UNIFORM HYPERGRAPH DETERMINED BY THE SIGNLESS LAPLACIAN MATRIX

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数学杂志 2025年第1期45卷 1-12页

作者： HE fang-guo College of Mathematics and Statistics Huanggang Normal UniversityHuBei 438000

This paper studies the problem of the spectral radius of the uniform hypergraph determined by the signless Laplacian *** upper bound of the spectral radius of a uniform hypergraph is obtained by using Rayleigh principle and the perturbation of the spectral radius under moving the edge operation,and the extremal hypergraphs are characterized for both supertree and unicyclic *** spectral radius of the graph is generalized.

关键词： spectral radius uniform hypergraph Signless Laplasian matrix

Interfacial Zn2+-solvation regulator towards reversible and stable Zn anode

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Journal of Energy Chemistry 2025年第1期100卷 684-692页

作者： Miao Zhou Xiongbin Luo Hang Li Shan guo Zhuang Tong Xiaotao Zhou Xu Li Zhaohui Hou Shuquan Liang guozhao fang College of Mechanical Engineering Key Laboratory of Hunan Province for Advanced Carbon-based Functional Materials Hunan Institute of Science and Technology School of Materials Science and Engineering Key Laboratory of Electronic Packaging and Advanced Functional Materials of Hunan Province Central South University College of Materials and Metallurgy Guizhou University National Energy Metal Resources and New Materials Key Laboratory Central South University

Aqueous zinc-ion batteries （AZIBs） are fundamentally challenged by the instability of the electrode/electrolyte interface,predominantly due to irreversible zinc （Zn） deposition and hydrogen ***,the intricate mechanisms behind the electrochemical discrepancies induced by interfacial Zn2+-solvation and deposition behavior demand comprehensive *** molecules endowed with special functional groups （such as hydroxyl,carboxyl,etc.） have the potential to significantly optimize the solvation structure of Zn2+and regulate the interfacial electric double layer （EDL）.By increasing nucleation overpotential and decreasing interfacial free energy,these functional groups facilitate a lower critical nucleation radius,thereby forming an asymptotic nucleation model to promote uniform Zn ***,this study presents a pioneering approach by introducing trace amounts of n-butanol as solvation regulators to engineer the homogenized Zn （H-Zn） anode with a uniform and dense *** interfacial reaction and structure evolution are explored by in/ex-situ experimental techniques,indicating that the H-Zn anode exhibits dendrite-free growth,no by-products,and weak hydrogen evolution,in sharp contrast to the bare ***,the H-Zn anode achieves a remarkable Zn utilization rate of approximately 20% and simultaneously sustains a prolonged cycle life exceeding 500 ***,the H-Zn//NH4V4O10（NVO） full battery showcases exceptional cycle stability,retaining 95.04%capacity retention after 400 cycles at a large current density of 5 A *** study enlightens solvation-regulated additives to develop Zn anode with superior utilization efficiency and extended operational lifespan.

关键词： Aqueous zinc-ion batteries Interfacial reaction Asymptotic nucleation model Reversible and stable Zn anode

The Analysis of Efficacy and Safety Profiles of Cetuximab In Chinese Patients With Colorectal Cancer

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The Analysis of Efficacy and Safety Profiles of Cetuximab In...

The low-latitude sodium layer:comparative data from lidar observations at Hainan,China and São Paulo,Brazil

第三届中国肿瘤内科大会

作者： Liang-ping Xia,gui-fang guo,Hui-juan Qiu,Bei Zhang,Fei-fei Zhou VIP region,Cancer Center,Sun Yat-sen University,National laboratory of oneology in southern China,Guangzhou,510060 R.P.China.

＜正＞Objective:The aim of this study was to investigate the efficacy and safety profiles of cetuximab,the commonly used monoclonal antibody of epidermal growth factor receptor,based on Chinese patients with colorectal *** and methods:All the papers studied on Chinese patients with gastrointestinal cancer treated by cetuximab and found in both databases of Chinese journal database for fulltext and PubMed were collected. The commonly used efficacy index such as disease control rate（CR+PR+SD） and response rate （CR+PR） were analyzed,and the cetuximab related side effects such acne-like rash and nail change and hypersensitivity were analyzed ***:（1）There were ten original papers contained total 152 patients with gastrointestinal cancer who were the candidates to analyze the safety profiles,and contained 130 patients with colorectal cancer who were candidates to analyze the efficacy.（2） The disease control rate and response rate in the whole group was 73.5%（95%CI:65.5%-81.5%） and 29.1%(95%CI:20.9%-

关键词： Chinese patient Colorectal cancer Cetuximab Efficacy Side effects epidermal growth factor receptor

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Earth and Planetary Physics 2025年第1期9卷 39-53页

作者： fang Wu Jing Jiao guoTao Yang Lifang Du ZhengKuan Liu HaoRan Zheng JiXin guo ShaoHua Gong YaJun Zhu State Key Laboratory of Space Weather National Space Science CenterChinese Academy of SciencesBeijing 100190China Hainan National Field Science Observation and Research Observatory for Space Weather National Space Science CenterChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China China-Brazil Joint Laboratory for Space Weather NSSC/INPESão Josédos Campos 12227-010Brazil School of Physics and Electronics Engineering Hainan Normal UniversityHaikou 571158China

Physical and chemical processes observed in the mesosphere and thermosphere above the Earth’s low latitudes are complex and highly interrelated to activity in the low-latitude *** sodium detected by lidar can yield clues to dynamic and chemical processes in these spatial layers above the Earth’s *** paper is based on sodium layer data collected at two low-latitude stations,one in the northern hemisphere and one in the *** low-latitude sodium layer exhibits conspicuous seasonal variations in shape,density,and altitude;these variations are similar between Earth’s hemispheres:sodium layer density at both stations reaches its seasonal maximum in autumn and minimum in ***,maximal Na density over Brazil is greater than that over *** variations of Na density above the two low-latitude stations are also similar;at both,maxima are observed before *** variations of the Na layer over Brazil that differ from those observed in the northern hemisphere may be related to the South Atlantic Magnetic Anomaly(SAMA)or fountain *** suggest that low-latitude Na layer data may provide useful additional evidence that could significantly improve the low-latitude part of the WACCM-Na model.

关键词： metallic sodium layer seasonal variation nocturnal variation lidar

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