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Cellular senescence:from anti-cancer weapon to anti-aging target

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Science China(Life Sciences) 2020年第3期63卷 332-342页

作者： Lifeng Yuan Peter BAlexander xiao-fan wang Program in Cellular and Molecular Medicine Boston Children’s HospitalBostonMA 02115USA Department of Genetics Harvard Medical SchoolBostonMA 02115USA Duke University Medical Center DurhamNC 27710USA

Cellular senescence(CS)is a state of stable cell cycle arrest characterized by the production and secretion of inflammatory *** studies described oncogene-induced senescence(OIS)as a barrier to tumorigenesis,such that the therapeutic induction of CS might represent a rational anti-cancer ***,the validity of this approach has been borne out by the development and approval of the cyclin-dependent kinase(CDK)inhibitor palbociclib for the treatment of breast *** from tumors,senescent cells have also been shown to accumulate during natural mammalian aging,where they produce detrimental effects on the physiology of surrounding ***,pharmacological senescent cell depletion has been proposed as an approach to delay age-related functional decline;this has been formally demonstrated in animal *** this review article,we describe the current mechanistic understanding of cellular senescence at the molecular level and how it informs the development of new therapeutic strategies to combat cancer and aging.

关键词： cellular senescence cancer healthy aging pro-senescence cancer therapy senolytic therapies

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Resistance to receptor tyrosine kinase inhibition in cancer： molecular mechanisms and therapeutic strategies

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Frontiers of Medicine 2015年第2期9卷 134-138页

作者： Peter B. Alexander xiao-fan wang Department of Pharmacology and Cancer Biology Duke University Medical Center Durham NC 27710 USA

Drug resistance is a major factor that limits the efficacy of targeted cancer therapies. In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitors, which are the most prevalent class of targeted therapeutic agent in current clinical use. Here we focus on bypass track resistance, which involves the activation of alternate signaling molecules by tumor cells to bypass inhibition and maintain signaling output, and consider the problems of signaling pathway redundancy and how the activation of different receptor tyrosine kinases translates into intracellular signal transduction in different cancer types. This information is presented in the context of research strategies for the discovery of new targets for pharmacological intervention, with the goal of overcoming resistance in order to improve patient outcomes.

关键词： targeted therapy drug resistance receptor tyrosine kinases cancer

The historical to future linkage of Arctic amplification on extreme precipitation over the Northern Hemisphere using CMIP5 and CMIP6 models

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Advances in Climate Change Research 2024年第4期15卷 573-583页

作者： Jun LIU xiao-fan wang Dong-You WU Xin wang Key Laboratory for Semi-Arid Climate Change of the Ministry of Education College of Atmospheric SciencesLanzhou UniversityLanzhou 730000China

Arctic warming played a dominant role in recent occurrences of extreme events over the Northern Hemisphere,but climate models cannot accurately simulate the *** a significant positive correlation(0.33-0.95)between extreme precipitation and Arctic amplification(AA)is found using observations and CMIP5/6 multi-model ***,CMIP6 models are superior to CMIP5 models in simulating the temporal evolution of extreme precipitation and *** to 14 optimal CMIP6 models,the maximum latitude of planetary waves and the strength of Northern Hemisphere annular mode(NAM)will increase with increasing AA,contributing to increased extreme precipitation over the Northern *** the Shared Socioeconomic Pathway SSP5-8.5,AA is expected to increase by 0.85℃ per decade while the maximum latitude of planetary waves will increase by 2.82°per ***,the amplitude of the NAM will increase by 0.21 hPa per decade,contributing to a rise in extreme precipitation of 1.17% per decade for R95pTOT and 0.86% per decade for R99pTOT by 2100.

关键词： Arctic amplification Extreme precipitation CMIP5 CMIP6 Model evaluation Planetary waves Northern hemisphere annular mode

Early changes in corneal densitometry after FS-LASIK combined with accelerated corneal cross-linking for correction of high myopia

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1307-1312页

作者： Qing-Bao wang Hong-Sheng Bi xiao-fan wang Hua fan Li Li Peng Ji Shandong University of Traditional Chinese Medicine Jinan 250014Shandong ProvinceChina Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine Shandong Clinical Medicine Research CenterJinan 250002Shandong ProvinceChina Shandong Academy of Eye Disease Prevention and Therapy Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular DiseasesJinan 250002Shandong ProvinceChina

AIM:To observe the effects of femtosecond laserassisted excimer laser in situ keratomileusis combined with accelerated corneal cross-linking(FS-LASIK Xtra)on corneal densitometry after correcting for high ***:In this prospectively study,130 patients underwent FS-LASIK or FS-LASIK Xtra for high *** right eyes were selected for inclusion in the study,of which 65 cases of 65 eyes in the FS-LASIK group,65 patients with 65 eyes in the FS-LASIK Xtra *** were evaluated for corneal densitometry at 1,3,and 6mo postoperatively using Pentacam Scheimpflug ***:Preoperative differences in corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups in different ranges were not statistically significant(P>0.05).Layer-by-layer analysis revealed statistically significant differences in the anterior(120μm),central,and total layer corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups at 1 and 3mo postoperatively(all P0.05).CONCLUSION:There is an increase in internal corneal densitometry during the early postoperative period after FS-LASIK Xtra for correction of high ***,the densitometry values decreased to the level of conventional FS-LASIK at 6mo after surgery,with the most significant changes observed in the superficial central zone.

关键词： femtosecond laser accelerated corneal cross-linking corneal densitometry high myopia femtosecond laser in situ keratomileusis

MiR-146a rs2910164 polymorphism increases risk of gastric cancer:A meta-analysis

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World Journal of Gastroenterology 2014年第41期20卷 15440-15447页

作者： Wen-Qun Xie Shi-Yun Tan xiao-fan wang Department of Gastroenterology Renmin Hospital of Wuhan University

AIM: To systematically evaluate the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer.

关键词： Gastric cancer MiR-146a Polymorphism Risk Meta-analysis

The hepatitis B virus-associated tumor microenvironment in hepatocellular carcinoma

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National Science Review 2014年第3期1卷 396-412页

作者： Pengyuan Yang Geoffrey J.Markowitz xiao-fan wang Department of Pharmacology and Cancer Biology Duke University Medical Center CAS Key Laboratory of Infection and Immunity Institute of Biophysics Chinese Academy of Sciences

In contrast to a majority of cancer types, the initiation of hepatocellular carcinoma(HCC) is intimately associated with a chronically diseased liver tissue, with one of the most prevalent etiological factors being hepatitis B virus(HBV). Transformation of the liver in HBV-associated HCC oten follows from or accompanies long-term symptoms of chronic hepatitis, inlammation and cirrhosis, and viral load is a strong predictor for both incidence and progression of HCC. Besides aiding in transformation, HBV plays a crucial role in modulating the accumulation and activation of both cellular components of the microenvironment,such as immune cells and ibroblasts, and non-cellular components of the microenvironment, such as cytokines and growth factors, markedly inluencing disease progression and prognosis. his review will explore some of these components and mechanisms to demonstrate both underlying themes and the inherent complexity of these interacting systems in the initiation, progression, and metastasis of HBV-positive HCC.

关键词： hepatitis B hepatocellular carcinoma tumor microenvironment leukocytes cytokines growth factors

Patient-derived organoids (PDOs) and PDO-derived xenografts (PDOXs): New opportunities in establishing faithful pre-clinical cancer models

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Journal of the National Cancer Center 2022年第4期2卷 263-276页

作者： Ergang wang Kun Xiang Yun Zhang xiao-fan wang Department of Pharmacology and Cancer Biology Duke UniversityDurhamUnited States State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

One of the major bottlenecks in advancing basic cancer research and developing novel cancer therapies is the lack of in vitro pre-clinical models that faithfully recapitulate tumor properties in the *** cultures of cancer cell lines usually lose the heterogeneity of the parental tumors,while patient-derived xenograft(PDX)suffers from its time-and resource-intensive *** emergence of organoid culture system and its application in cancer research provides a unique opportunity to develop novel in vitro cancer pre-clinical *** we review the recent advances in utilizing organoids culture system and other related three-dimensional culture systems in studying cancer biology,performing drug screening,and developing cancer *** particular,we discuss the advantages of applying xenograft initiated from patient-derived organoids(PDOs)as a faithful cancer pre-clinical model in basic cancer research and precision medicine.

关键词： Patient-derived organoid Patient-derived xenograft PDO-derived xenograft

Production of male flowers does not decrease with plant sizein insect-pollinated Sagittaria trifolia,contrary to predictionsof size-dependent sex allocation

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Journal of Systematics and Evolution 2011年第5期49卷 379-385页

作者： Bing HAN xiao-fan wang Shuang-Quan HUANG(College of Life Sciences,Wuhan University,Wuhan 430072,China) (College of Life Sciences Wuhan University Wuhan 430072 China)

It has been proposed that relative allocation to female function increases with plant size in animalpollinated *** investigations in several monoecious Sagittaria species seem to run contrary to the prediction of size-dependent sex allocation(SDS),throwing doubt on the generalization of *** size,phenotypic gender,and flower production were measured in experimental populations of an aquatic,insect-pollinated herb Sagittaria trifolia(Alismataceae) under highly different *** comparison of ramets produced clonally can reduce confounding effects from genetic and environmental *** the high-density population,48% of ramets were male without female flowers,but in the low-density population all ramets were *** observed allometric growth in reproductive allocation with ramet size,as evident in biomass of reproductive structures and number of ?***,within both populations female and male flower production were isometric with ramet size,in contrast to an allometric growth in femaleness as predicted by *** gender was not related to ramet size in either *** results indicated that large plants may increase both female and male function even in animal-pollinated plants,pointing towards further studies to test the hypothesis of size-dependent sex allocation using different allocation currencies.

关键词： Alismataceae clonal reproduction ?ower production insect-pollinated monoecious Sagittaria trifolia size-dependent sex allocation.

Pre-and post-pollination barriers between two exotic and five native Sagittaria species:Implications for species conservation

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Plant Diversity 2023年第4期45卷 456-468页

作者： Ting-Ting Zou Sen-Tao Lyu Qi-Lin Jiang Shu-He Shang xiao-fan wang Laboratory of Plant Systematics and Evolutionary Biology College of Life SciencesWuhan UniversityWuhan 430072China

Anthropogenic introduction of species has resulted in a breakdown of geographical barriers and hybridization in previously allopatric ***,examining hybridization proneness of exotic species contributes to revealing its potential ***,reproductive barriers may be strengthened or weakened due to long-term geographical isolation for these newly sympatric ***,few studies have evaluated multiple barriers between alien and native *** this study,we quantified the importance of four pre-pollination barriers(phenological,floral traits,pollen production,and floral constancy)and four post-pollination barriers(pollen-pistil incompatibility,seed set,seed viability,and seedling survival)between two introduced and five native Sagittaria *** showed that introduced *** was cross-compatible with two native species,whereas introduced *** was incapable of hybridizing with any native *** barriers were asymmetric within species pairs and multiple barriers acted in concert to maintain species *** barriers contributed more to total reproductive isolation in native species,whereas prepollination barriers played a stronger role in total reproductive isolation for two introduced *** set was the only barrier that was positively correlated with genetic *** results provide a perspective to better understand reproductive barriers for secondary contact *** highlight the importance of monitoring hybridization events before human introduction and the possible conservation strategies to remove invasive species with hybridization proneness.

关键词： Alismataceae Introduced species Conservation Hybridization Reproductive isolation Sagittaria

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