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Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies

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Cancer Biology & Medicine 2014年第1期11卷 1-19页

作者： liem minh phan Sai-Ching Jim Yeung Mong-Hong Lee Department of Molecular and Cellular Oncology Department of General Internal Medicine Ambulatory Treatment and Emergency Care Department of Endocrine Neoplasia and Hormonal Disorders The University of Texas MD Anderson Cancer Center

Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistance to cancer treatments. Since Dr. Otto Warhurg＇s discovery about altered cancer cell metabolism in 1930, thousands of studies have shed light on various aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism. This review highlights the importance of the main features of cancer metabolism, summarizes recent remarkable advances in this field, and points out the potentials to translate these scientific findings into life-saving diagnosis and therapies to help cancer patients.

关键词： Cell cycle energy metabolism glycolysis glutaminolysis mitochondria biogenesis

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Impact of diabetes on promoting the growth of breast cancer

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Cancer Communications 2021年第5期41卷 414-431页

作者： Ping-Chieh Chou Hyun Ho Choi Yizhi Huang Enrique Fuentes-Mattei Guermarie Velazquez-Torres Fanmao Zhang liem phan Jaehyuk Lee Yanxia Shi James A.Bankson Yun Wu Huamin Wang Ruiying Zhao Sai-Ching Jim Yeung Mong-Hong Lee Department of Molecular and Cellular Oncology the University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Guangdong Provincial Key laboratory of Colorectal and Pelvic Floor Disease the Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510020P.R.China Research Institute of Gastroenterology the Sixth Affiliated Hospital of Sun Yat-sen University GuangzhouGuangdong 510020P.R.China Department of Imaging Physics the University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Department of Pathology the University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Emergency Medicine the University of Texas MD Anderson Cancer CenterHoustonTX 77030USA

Background:Type Ⅱ diabetes mellitus(DM2)is a significant risk factor for cancers,including breast ***,a proper diabetic breast cancer mouse model is notwell-established for treatment strategy ***,the precise diabetic signaling pathways that regulate cancer growth remain *** the present study,we established a suitable mouse model and demonstrated the pathogenic role of diabetes on breast cancer ***:We successfully generated a transgenic mouse model of human epidermal growth factor receptor 2 positive(Her2^(+) or ERBB2)breast cancer with DM2 by crossing leptin receptor mutant(Lepr^(db/+))mice with (MMTV-ErbB2/neu)*** administrated with antidiabetic drugs to assess the impacts of controlling DM2 in affecting tumor *** resonance spectroscopic imaging was employed to analyze the tumor ***:Treatment with metformin/rosiglitazone in MMTV-ErbB2/Lepr^(db/db) mousemodel reduced serum insulin levels,prolonged overall survival,decreased cumulative tumor incidence,and inhibited tumor ***-insulin resistance medications also inhibited glycolytic metabolism in tumors in vivo as indicated by the reduced metabolic flux of hyperpolarized ^(13)C pyruvate-to-lactate *** tumor cells from MMTV-ErbB2/Lepr^(db/db) transgenic mice treated with metformin had reprogrammed metabolism by reducing levels of both oxygen consumption and lactate *** decreased the expression of Myc and pyruvate kinase isozyme 2(PKM2),leading to metabolism ***,metformin attenuated the mTOR/AKT signaling pathway and altered adipokine ***:MMTV-ErbB2/Lepr^(db/db) mouse model was able to recapitulate diabetic HER2^(+) human breast ***,our results defined the signaling pathways deregulated in HER2^(+) breast cancer under diabetic condition,which can be intervened by anti-insulin resistance therapy.

关键词： diabetes human epidermal growth factor receptor 2 breast cancer metformin metabolism

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Stem cell-based therapy for human diseases

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3242-3282页

作者： Duc M.Hoang Phuong T.Pham Trung Q.Bach Anh T.L.Ngo Quyen T.Nguyen Trang T.K.phan Giang H.Nguyen Phuong T.T.Le Van T.Hoang Nicholas R.Forsyth Michael Heke liem Thanh Nguyen Department of Research and Development Vinmec Research Institute of Stem Cell and Gene TechnologyVinmec Healthcare SystemHanoiVietnam Department of Cellular Therapy Vinmec High.Tech CenterVinmec Healthcare SsystemHanoiVietnam Institute for Science&Technology in Medicine Keele UniversityKeeleUK a Department of Biology Stanford UniversityStanfordCAUSA

Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be *** cell-based therapy,including human pluripotent stem cells(hPsCs)and multipotent mesenchymal stem cells(MSCs),has recently emerged as a key player in regenerative *** are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body,including three germ *** are multipotent progenitor cells possessing self-renewal ability(limited in vitro)and differentiation potential into mesenchymal lineages,according to the International Society for Cell and Gene Therapy(ISCT).This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow(BM),adipose tissue(AT),or the umbilical cord(UC)for the treatment of human diseases,including neurological disorders,pulmonary dysfunctions,metabolic/endocrine-related diseases,reproductive disorders,skin burns,and cardiovascular ***,we discuss our own clinical trial experiences on targeted therapies using MsCs in a clinical setting,and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications,with the ultimate objective of facilitating translational research in regenerative medicine into clinical *** mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment,AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration,and UC-MsCs are potentially good candidates for pulmonary disease and acute respiratory distress svndrometreatment.

关键词： diseases distress treatment

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糖尿病对促进乳腺癌生长的影响

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癌症 2022年第3期41卷 107-124页

作者： Ping-Chieh Chou Hyun Ho Choi Yizhi Huang Enrique Fuentes-Mattei Guermarie Velazquez-Torres Fanmao Zhang liem phan Jaehyuk Lee Yanxia Shi James A.Bankson Yun Wu Huamin Wang Ruiying Zhao Sai-Ching Jim Yeung Mong-Hong Lee Department of Molecular and Cellular Oncology the University of Texas MD Anderson Cancer CenterHoustonTX 77030USA 结直肠盆底疾病研究重点实验室中山大学第六附属医院广州广东510020 胃肠病学研究所中山大学第六附属医院广州广东510020 Department of Imaging Physics the University of Texas MD Anderson Cancer CenterHoustonTX 77030USA 中山大学肿瘤防治中心肿瘤内科广州广东510060 Department of Pathology the University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Emergency Medicine the University of Texas MD Anderson Cancer CenterHoustonTX 77030USA

背景与目的2型糖尿病(typeⅡdiabetes mellitus,DM2)是包括乳腺癌在内的多种癌症的危险因素。目前,尚未建立可用于研究的糖尿病乳腺癌小鼠模型。另外,调节癌症生长的糖尿病信号通路也尚未明确。在本研究中,我们建立了一个糖尿病乳腺癌... 详细信息

背景与目的2型糖尿病(typeⅡdiabetes mellitus,DM2)是包括乳腺癌在内的多种癌症的危险因素。目前,尚未建立可用于研究的糖尿病乳腺癌小鼠模型。另外,调节癌症生长的糖尿病信号通路也尚未明确。在本研究中,我们建立了一个糖尿病乳腺癌小鼠模型,并证实了糖尿病在乳腺癌进展中的影响。方法通过将瘦素受体突变(Lepr^(db/+))小鼠和MMTV-ErbB2/neu小鼠杂交,成功构建了人表皮生长因子受体2阳性(human epidermal growth factor receptor 2,Her2^(+)或ERBB2)的乳腺癌转基因小鼠模型。用抗糖尿病药物治疗该小鼠模型来评价治疗DM2对肿瘤生长的影响。用磁共振波谱成像分析肿瘤代谢情况。结果用二甲双胍/罗格列酮治疗MMTV-ErbB2/Lepr^(db/db)小鼠模型可降低血清胰岛素水平,延长生存,降低肿瘤累积发生率,抑制肿瘤进展。超极化^(13)C标记的丙酮酸/乳酸转换代谢流降低,表明抗胰岛素抵抗治疗抑制了体内实验中肿瘤糖酵解。用二甲双胍处理MMTV-ErbB2/Lepr^(db/db)转基因小鼠来源的肿瘤细胞,降低了耗氧量和乳酸产量,使细胞代谢发生了重新编程。二甲双胍可降低Myc和丙酮酸激酶M2型同工酶(pyruvate kinase isozyme 2,PKM2)的表达,引起代谢重编程。另外,二甲双胍可阻断mTOR/AKT信号通路并改变脂肪因子谱。结论MMTV-ErbB2/Lepr^(db/db)转基因小鼠模型可用于糖尿病HER2^(+)人乳腺癌的研究。本研究明确了糖尿病状态下HER2^(+)人乳腺癌中失调的信号通路,该通路可被抗胰岛素抵抗治疗干预。

关键词：糖尿病人表皮生长因子受体2 乳腺癌二甲双胍代谢

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Ecoregional variations of aboveground biomass and stand structure in evergreen broadleaved forests

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Journal of Forestry Research 2020年第5期31卷 1713-1722页

作者： Tran Van Do Mamoru Yamamoto Osamu Kozan Vo Dai Hai Phung Dinh Trung Nguyen Toan Thang Lai Thanh Hai Vu Thanh Nam Trieu Thai Hung Hoang Van Thang Tran Duc Manh Cao Chi Khiem Vu Tien Lam Nguyen Quang Hung Tran Hoang Quy Pham Quang Tuyen Trinh Ngoc Bon Nguyen Thi Thu Phuong Ninh Viet Khuong Nguyen Van Tuan Dang Thi Hai Ha Tran Hai Long Dang Van Thuyet Dang Thinh Trieu Nguyen Van Thinh Tran Anh Hai Duong Quang Trung Nguyen Van Bich Dinh Hai Dang Pham Tien Dung Nguyen Huy Hoang Le Thi Hanh phan minh Quang Nguyen Thi Thuy Huong Hoang Thanh Son Nguyen Thanh Son Nguyen Thi Van Anh Nguyen Thi Hoai Anh Pham Dinh Sam Hoang Thi Nhung Hoang Van Thanh Nguyen Huu Thinh Tran Hong Van Ho Trung Luong Bui Kieu Hung Research Institute for Sustainable Humanosphere Kyoto UniversityUjiKyotoJapan Silviculture Research Institute Vietnamese Academy of Forest SciencesNorth Tu LiemHanoiVietnam Center for Southeast Asian Studies Kyoto UniversityKyotoJapan Vietnamese Academy of Forest Sciences North Tu LiemHanoiVietnam Vietnam Administration of Forestry No.2 Ngoc HaBa DinhHanoiVietnam

Biotic and abiotic factors control aboveground biomass(AGB)and the structure of forest *** study analyses the variation of AGB and stand structure of evergreen broadleaved forests among six ecoregions of Vietnam.A data set of 1731-ha plots from 52 locations in undisturbed old-growth forests was *** results indicate that basal area and AGB are closely correlated with annual precipitation,but not with annual temperature,evaporation or hours of *** area and AGB are positively correlated with trees>30 cm *** areas surveyed(52.6%)in these old-growth forests had AGB of 100–200 Mg ha^-1;5.2%had AGB of 400–500 Mg ha^-1,and 0.6%had AGB of>800 Mg ha^-*** percent of the areas surveyed had stand densities of 300–600 ***^-1,and 64%had basal areas of 20–40 m^2 ha^-*** is an important factor influencing the AGB of old-growth,evergreen broadleaved forests in *** causing the loss of large-diameter trees(e.g.,>100 cm DBH)affects AGB but may not seriously affect stand density.

关键词： Aboveground biomass Carbon storage Climatic variables Ecoregion Edaphic variables Oldgrowth forest

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