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Genome-wide Discovery and Clinical Validation of Pharmacogenomic Markers for Chemotherapy

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Genome-wide Discovery and Clinical Validation of Pharmacogen...

Methoprene does not affect juvenile hormone titers in honey bee （Apis mellifera） workers

第十届全国化疗药理暨抗感染药理高峰论坛

作者： r.stephanie huang University of Chicago

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Insect Science 2018年第2期25卷 235-240页

作者： Zachary Y. huang stephanie Lin Kiheung Ahn Department of Entomology Michigan State University East Lansing Michigan USA Ecology Evolutionary Biology and Behavior Michigan State University East Lansing Michigan USA BEACON Center for the Study of Evolution in Action Michigan State University East Lansing Michigan USA and 4High School Honors Science Program 2007 Michigan State University East Lansing Michigan USA

Methoprene, a juvenile hormone （JH） analog, is a widely used insecticide that also accelerates behavioral development in honey bees （Apis mellifera）. JH regulates the transition from nursing to foraging in adult worker bees, and treatment with JH or methoprene have both been shown to induce precocious foraging. To determine how methoprene changes honey bee behavior, we compared JH titers ofmethoprene-treated and untreated bees. Behavioral observations confirmed that methoprene treatment significantly increased the number of precocious foragers in 3 out of 4 colonies. In only 1 out of 4 colonies, however, was there a significant difference in JH titers between the methoprene- treated and control bees. Further, in all 4 colonies, there was no significant differences in JH titers between precocious and normal-aged foragers. These results suggest that methoprene did not directly affect the endogenous JH secreted by corpora allata. Because methoprene caused early foraging without changing workers＇ JH titers, we conclude that methoprene most likely acts directly on the JH receptors as a substitute for JH.

关键词： behavioral development juvenile hormone analog juvenile hormone metho-prene precocious foraging

The Promise of Pharmacogenomics in reducingToxicity During Acute Lymphoblastic LeukemiaMaintenance Treatment

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Genomics, Proteomics & Bioinformatics 2017年第2期15卷 82-93页

作者： Shoshana rudin Marcus Marable r. stephanie huang Biological Sciences Division University of Chicago Chicago IL 60637 USA Department of Medicine University of Chicago Chicago IL 60637 USA

Pediatric acute lymphoblastic leukemia(ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2–3 years. While the primary drugs used in the maintenance phase, 6-mercaptopurine(6-MP) and methotrexate(MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity. For both drugs, pharmacogenomic factors have been identified that could explain a large amount of the variance in toxicity between patients, and may serve as effective predictors of toxicity during the maintenance phase of ALL treatment.6-MP toxicity is associated with polymorphisms in the genes encoding thiopurine methyltransferase(TPMT), nudix hydrolase 15(NUDT15), and potentially inosine triphosphatase(ITPA), which vary between ethnic groups. Moreover, MTX toxicity is associated with polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1(SLCO1B1) and dihydrofolate reductase(DHFr). Additional polymorphisms potentially associated with toxicities for MTX have also been identified, including those in the genes encoding solute carrier family 19 member 1(SLC19A1)and thymidylate synthetase(TYMS), but their contributions have not yet been well quantified. It is clear that pharmacogenomics should be incorporated as a dosage-calibrating tool in pediatric ALL treatment in order to predict and minimize the occurrence of serious toxicities for these patients.

关键词： Acute lymphoblastic leukemia 6-Mercaptopurine Methotrexate Pharmacogenomics Maintenance therapy

Pharmacogenomics of EGFr-targeted therapies in non-small cell lung cancer:EGFr and beyond

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Chinese Journal of Cancer 2015年第4期34卷 149-160页

作者： Christopher Delaney Samuel Frank r.stephanie huang Biological Sciences Division University of Chicago Department of Medicine University of Chicago The Affiliated Hospital School of MedicineNingbo University

Commonly observed aberrations in epidermal growth factor receptor(EGFr) signaling have led to the development of EGFr-targeted therapies for various cancers,including non-small cell lung cancer(NSCLC).EGFr mutations and overexpression have further been shown to modulate sensitivity to these EGFr-targeted therapies in NSCLC and several other types of ***,it is clear that mutations and/or genetic variations in EGFr alone cannot explain all of the variability in the responses of patients with NSCLC to EGFr-targeted *** instance,in addition to EGFr genotype,genetic variations in other members of the signaling pathway downstream of EGFr or variations in parallel receptor tyrosine kinase(rTK) pathways are now recognized to have a significant impact on the efficacy of certain EGFr-targeted *** this review,we highlight the mutations and genetic variations in such genes downstream of EGFr and in parallel rTK ***,the directional effects of these pharmacogenetic factors are discussed with a focus on two commonly prescribed EGFr inhibitors:cetuximab and *** results of this comprehensive review can be used to optimize the treatment of NSCLC with EGFr ***,they may provide the rationale for the design of subsequent combination therapies that involve the inhibition of EGFr.

关键词：表皮生长因子受体非小细胞肺癌药物基因组学 EGFr 靶向治疗信号传导途径受体酪氨酸激酶遗传变异

Nut and peanut butter consumption and risk of prostate cancer in the NIH-AArP diet and health study

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Cancer Communications 2022年第1期42卷 65-69页

作者： Mimi Ton Leah M.Ferrucci stephanie J.Weinstein Maryam Hashemian Demetrius Albanes Jiaqi huang Metabolic Epidemiology Branch Division of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaMD 20892United States Yale School of Public Health Yale UniversityNew HavenCT 06520United States Yale Cancer Center Yale UniversityNew HavenCT 06520United States Department of Biology School of Arts and SciencesUtica CollegeUticaNY 13502United States National Clinical research Center for Metabolic Diseases Key Laboratory of Diabetes ImmunologyMinistry of Educationand Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China

Dear Editor,Prostate cancer is the second most common cancer among men worldwide and leading cancer in incidence among men in the United States(US).In 2018,the US had over 190,000 new prostate cancer cases,accounting for almost 1 in 5 new male cancer diagnoses[1].A recent review of dietary factors in relation to prostate cancer risk did not find evidence regarding nut consumption as neither a risk nor protective factor,though it has been hypothesized to be associated with a decreased cancer risk through multi-ple mechanisms[2].

关键词： protective cancer dietary

Targeting glutamine metabolism enhances responses to platinum-based chemotherapy in triple-negative breast cancers(TNBC)

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Genes & Diseases 2022年第6期9卷 1408-1411页

作者： Jiaxin Hong Yao-An Shen Chih-Yi Hsu Peng huang Alicja Tomaszewski Edward Gabrielson Ie-Ming Shih stephanie Gaillard Tian-Li Wang Sidney Kimmel Comprehensive Cancer Center and Department of Oncology BaltimoreMD 21231USA Department of Pathology Johns Hopkins University School of MedicineBaltimoreMD 21231USA Cancer Center Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022PR China Department of Gynecology and Obstetrics Johns Hopkins University School of MedicineBaltimoreMD 21231USA

reprogramming of metabolic pathways,a hallmark of human cancer,results from a process in which cancer cells become dependent on specific metabolic pathways such as glutamine catabolism or glutaminolysis for growth and *** studies have demonstrated that triplenegative breast cancers(TNBC)may use glutamine as an extracellular nutrient source to generate lipids,proteins,and nucleic acids.1 Glutamine catabolism in cancer cells also contributes to the production of the antioxidant,glutathione(GSH),which is critical for redox homeostasis and for protection of cells from oxidative stress elicited by reactive oxygen species(rOS).2 Considering TNBC cell lines are often dependent on glutamine for growth and survival,we sought to determine whether targeting glutaminolysis with a small molecule inhibitor,CB-839,in combination with platinum-based chemotherapy drug,would elicit significant anti-tumor activity.

关键词： metabolism TNBC chemotherapy

Case report: rhabdomyolysis in the setting of acute human immunodeficiency virus infection

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Case reports in Clinical Medicine 2013年第3期2卷 198-202页

作者： Jason C. huang stephanie Gold Kathleen A. McManus Brian Wispelwey Department of Family Medicine University of Colorado Denver Colorado USA Department of Medicine University of Virginia Charlottesville Virginia USA Division of Infectious Diseases and International Health Department of Medicine University of Virginia Charlottesville USA

Acute HIV infection (AHI) is often marked by nonspecific and vague complaints, which make detection difficult. An 18-year-old man presented with one week history of subjective fevers with chills, nonproductive cough and generalized body aches. He was found to have rhabdomyolysis due to AHI. This report adds the most thoroughly investigated case of AHI-associated rhabdomyolysis to date, having ruled out erlichia, legionella, parainfluenza, adenovirus, enterovirus, metapneumovirus, rSV and DILS.

关键词： Acute HIV Infection rhabdomyolysis HIV Primary HIV

Elevated preoperative neutrophil-tolymphocyte ratio may be associated with decreased overall survival in patients with metastatic clear cell renal cell carcinoma undergoing cytoreductive nephrectomy

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Asian Journal of Urology 2016年第1期3卷 20-25页

作者： Yoram S.Baum Dattatraya Patil Jonathan H.huang stephanie Spetka Mersiha Torlak Peter T.Nieh Mehrdad Alemozaffar Kenneth Ogan Viraj A.Master Department of Urology Emory University School of MedicineAtlantaGAUSA

Objective:Inflammatory serum markers have proven to be a powerful predictive tool of patient prognosis in cancer treatment for a wide variety of solid organ malignancies,predominantly in the context of localized *** this study we evaluated the preoperative neutrophil-to-lymphocyte ratio(NLr)as a predictive tool in patients with metastatic clear cell renal cell carcinoma(rCC).Methods:Sixty-four patients with metastatic clear cell rCC undergoing nephrectomy were *** patients with preoperative NLr were included for survival *** were categorized into high and low NLr score determined by plotting the NLr rOC *** analysis was ***:Median age was 60.8 years(38.2-81.2).Median follow-up time was 8.1 months(0.1-106.3).Fuhrman grade distribution was:2(3.1%)grade 1,6(9.4%)grade 2,24(37.5%)grade 3 and 32(50.0%)grade *** NLr score was 3.5(1.4-31.0).NLr4 was associated with decreased overall survival compared toNLrriable survival analysis showed NLr4 as an independent predictor of survival(Hazard ratio(Hr)2.41,95%CI 1.05-5.50,p=0.03).Conclusion:Elevated preoperative NLr is associatedwith poor prognosis in patients withmetastatic kidney *** NLr is a useful tool,which can predict prognosis,stratify patients for postoperative surveillance,and help guide decisions for therapy.

关键词： renal cancer Neutrophil-tolymphocyte ratio Cytoreductive nephrectomy Prognosis

Comparative transcriptomics and gene network analysis revealed secondary metabolism as preeminent metabolic pathways for heat tolerance in hard fescue

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Grass research 2021年第1期1卷 110-119页

作者： Yi Xu stephanie rossi Bingru huang Department of Plant Biology RutgersThe State University of New JerseyNew BrunswickNJ 08901USA

The molecular mechanisms underlying genetic variations in heat tolerance,one of the important turfgrass traits,for fine fescue are not *** the present study,our objective was to identify molecular constituents and metabolic interactions involved in heat tolerance in two genotypes of hard fescue(Festuca trachyphylla)contrasting in heat tolerance by comparative transcriptomics and gene comparison network *** cultivars of hard fescue,'reliant IV'(heat-tolerant),and'Predator'(heat-sensitive),were subjected to heat stress temperature at 35/30℃(day/night)or maintained at optimal temperature at 22/18℃(day/night)(non-stress control)for 21 *** 14 and 21 d of heat stress,'reliant IV'maintained significantly higher photochemical efficiency(F_(v)/F_(m)),chlorophyll(Chl)content,and lower cell membrane electrolyte leakage(EL)compared to'Predator',suggesting its superiority in heat *** transcriptomic profiles,gene functional enrichment analysis,and weighted gene comparison network analysis revealed central hub genes(BBE22 and ALPLD)and their connecting genes involved in secondary metabolism for biosynthesis of oxylipins(LOX1 and LOX3),phenolic compounds(PAL2),and dhurrin(C79A1 and C71E1).These genes were up-regulated in heat-tolerant'reliant IV'under heat stress but not in heat-sensitive'Predator',while a majority of heat-regulated genes involved in primary metabolism responded similarly to heat stress in both *** unique genes in the secondary metabolic pathways enriched in only the heat-tolerant cultivar could be critical for mediating the protection of hard fescue against heat stress and are potentially useful as candidate genes or molecular markers for augmenting heat tolerance in other temperate species of grass.

关键词： metabolism network maintained