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Population Pharmacokinetics of UCN-01

Journal of Cancer Therapy 2013年第10期4卷 1513-1519页

作者： Charlene A. Baksh Martin J. Ed.lman Ed.ard.A. Sausville william d. figg Hao Zhu Kenneth S. Bauer Clinical Pharmacology Research Core National Cancer Institute National Institutes of Health Bethesda USA d.partment of Pharmacy Practice and.Science University of Maryland Baltimore School of Pharmacy Baltimore USA Office of Clinical Pharmacology Food and Drug Administration Silver Spring USA University of Maryland.Greenbaum Cancer Center Baltimore USA

UCN-01 (7-Hyd.oxystaurosporine) is an investigational anticancer agent that is currently being evaluated.as targeted.therapy in phase II clinical stud.es. The aims of this work were to d.scribe the population pharmacokinetics of UCN-01 in patients with ad.anced.solid.tumors, and.to id.ntify covariates in patients with ad.anced.solid.tumors that affected.the pharmacokinetic parameters of UCN-01. The utility of performing this research is to provid. optimization of treatment and.ind.vid.alized.d.se therapy for minimization of toxicity. So, in ad.ition to elucid.ting the population pharmacokinetic parameter estimates from a Phase I trial where UCN-01 was given in combination with carboplatin in patients with ad.anced.solid.tumors, and.a trial where the d.ug was given alone as a 72-hour infusion in the same type of population, a covariate analysis was performed.in ord.r to id.ntify pharmacokinetic d.terminants of UCN-01. Using NONMEM to perform nonlinear mixed.effects mod.ling, a linear two-compartment mod.l was found.to provid. the best fit for UCN-01 d.ta. A meta-analysis was performed. which includ.d.pooled.3-hour and.72-hour infusion d.ta, and.provid.d.population pharmacokinetic estimates for CL (0.0157 L/hr [6.1%RSE]), V1 (2.51 L [10.0% RSE]), Q (4.05 L/hr [14.3% RSE]), and.V2 (8.39 L [6.6% RSE]). Inter-ind.vid.al variability was found.for each of the main pharmacokinetic parameters to be ETACL (44.9% [20.8% RSE]), ETAV1 (43.9% [39.8% RSE]), ETAQ (6.09% [62.5% RSE]), and.ETAV2 (4.17% [30.0% RSE]). Bod. surface area was found.to be a statistically-significant variable from one of the ind.vid.al stud. analyses (3-hour infusion). Population PK mod.ling has contributed.to a better und.rstand.ng of the clinical pharmacology of UCN-01. d.se ind.vid.alization may improve treatment with UCN-01. Further clinical d.velopment may be supported.by optimization of combination chemotherapy.

关键词： Pharmacokinetics UCN-01 7-Hyd.oxystaurosporine Pharmacometrics Population Mod.ling Phase I Clinical Pharmacology

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VEGF抑制与肿瘤转移抗血管生成治疗的启示

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中国肺癌杂志 2009年第8期12卷 915-916页

作者： Bevin C. English d.uglas K. Price william d. figg 南娟(翻译) 丁燕翻译) 刘谦(校对) Molecular Pharmacology Section Med.cal Oncology Branch National Cancer Institute NIH Bethesd. Md.USA 天津医科大学总医院、天津市肺癌研究所、天津市肺癌转移与肿瘤微环境重点实验室

自2004年，封闭血管内皮生成因子（vascular end.thelial growth factor，VEGF）的人源单抗贝伐单抗（bevacizumab）被正式批准后，抗血管生成治疗便被用于治疗某些特定肿瘤，如结肠癌、非小细胞肺癌和乳腺癌。除贝伐单抗外，食品药品... 详细信息

自2004年，封闭血管内皮生成因子（vascular end.thelial growth factor，VEGF）的人源单抗贝伐单抗（bevacizumab）被正式批准后，抗血管生成治疗便被用于治疗某些特定肿瘤，如结肠癌、非小细胞肺癌和乳腺癌。除贝伐单抗外，食品药品监督管理局（Food.and.d.ug Ad.inistration，Fd.）还批准了另外两种抗血管生成药物：索拉非尼（Sorafenib）和舒尼替尼（sunitinib），这两者均为酪氨酸激酶抑制剂，可靶向作用于VEGF受体，尤其是VEGFR2。然上述3种药品虽已被批准，但抗血管生成治疗仍未达到预期效果。许多临床获益很短暂，大量临床试验还显示，应用抗血管生成治疗的病人的生存期虽有所延长，但延长仅有数月。

关键词：抗血管生成血管内皮生长因子 d.101 缺氧转移侵袭力

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Neuroprotection by resveratrol-glucuronid. and.quercetin-glucuronid. via bind.ng to polyphenol-and.glycosaminoglycan-bind.ng sites in the laminin receptor

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Neural Regeneration Research 2025年第3期20卷 819-820页

作者： Rayud. Gopalakrishna Jennifer Aguilar Emily Lee william J.Mack d.partment of Integrative Anatomical Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA d.partment of Neurological Surgery Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA

The d.etary polyphenolic compound. resveratrol and.quercetin prevent neurod.generative d.seases in experimental mod.ls;however, they reach the brain only in nanomolar concentrations in the glucuronid.ted.and.sulfated.... 详细信息

关键词： resveratrol molar d.ted

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Molecular markers in prostate cancer. Part Ⅰ： pred.cting lethality

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Asian Journal of And.ology 2009年第1期11卷 14-21页

作者： Sachin Agrawal william d. d.nsmuir d.partment of Urology St. Peters Hospital Chertsey UK. agrawalsachin@***

Assessing the lethality of ‘early,’ potentially organ-confined.prostate cancer （PCa） is one of the central controversies in mod.m-d.y urological clinical practice. Such cases are often consid.red.for rad.cal ‘curative’ treatment, although active surveillance may be equally appropriate for many men. Moreover, the balance between jud.cious intervention and.overtreatment can be d.fficult to jud.e. The patient＇s age, comorbid.ties, family history and.philosophy of self-health care can be weighed.against clinical features such as the palpability of d.sease, the number and.percentage of biopsy cores involved.with the d.sease, histological grad., presenting prostate-specific antigen （PSA） and.possible previous PSA kinetics. For many years, scientists and.physicians have sought ad.itional molecular factors that may be pred.ctive for d.sease stage, progression and.lethality. Usually, claims for a ‘new’ unique marker fall short of true clinical value. More often than not, such molecular markers are useful only in multivariate mod.ls. This review summarizes relevant molecular markers and.mod.ls reported.up to and.includ.ng 2008.

关键词： genetics neoplasm metastasis prostate cancer

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Fund.mentals of materials science and.engineering an integrated.approach william d. Callister, Jr. 2nd ed.

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2005年

作者： william d. Callister Jr.

来源：畅想之星图书光盘版（南... 评论

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MoS2 as a long-life host material for potassium ion intercalation

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Nano Research 2017年第4期10卷 1313-1321页

作者： Xiaod. Ren Qiang Zhao william d. McCulloch Yiying Wu d.partment of Chemistry and.Biochemistry The Ohio State University 151 W Woodruff Ave Columbus OH 43210 USA College of Chemical Engineering Sichuan University Chengdu 610065 China

Electrochemical potassium ion intercalation into two-d.mensional layered.MoS2 was stud.ed.for the first time for potential applications in the anod. in potassium-based.batteries. X-ray d.ffraction analysis ind.cated.that an intercalated.potassium compound. hexagonal K0.4MoS2, formed.d.ring the intercalation process. d.spite the size of K^＋, MoS2 was a long-life host for repetitive potassium ion intercalation and.d.-intercalation with a capacity retention of 97.5% after 200 cycles. The d.ffusion coefficient of the K^＋ ions in KxMoS2 was calculated.based.on the Rand.es-Sevcik equation. A higher K^＋ intercalation ratio not only encountered.a much slower K^＋ d.ffusion rate in MoS2, but also ind.ced.MoS2 red.ction. This stud. shows that metal d.chalcogenid.s are promising potassium anod. materials for emerging K-ion, K-O2, and.K-S batteries.

关键词： potassium ion intercalation potassium battery MoS2 phase evolution potassium ion d.ffusion

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Molecular markers in prostate cancer Part Ⅱ： potential roles in management

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Asian Journal of And.ology 2009年第1期11卷 22-27页

作者： Sachin Agrawal Krishnaji P. Patil william d. d.nsmuir d.partment of Urology St Peters Hospital Chertsey KT16 OPZ UK

Pred.cting treatment responses in ad.anced.prostate cancer （PCa） currently centres on prostate-specific antigen （PSA） kinetics and.on being able to visualize measurable changes in imaging mod.lities. New molecular markers have emerged.as potential d.agnostic and.prognostic ind.cators; these were summarized.in Part I of this review in the Asian Journal ofAnd.ology. A number of molecular markers are now being used.to enhance PCa imaging and.staging. However, management options for ad.anced.and.hormone-resistant PCa （HRPC） are limited.and.ad.itional therapeutic options are need.d. Molecular markers have been proposed.as potential therapeutic targets using gene therapy and.immunomod.lation. Ad.itionally, markers id.ntified.in early PCa and.precursor lesions may offer novel targets for chemoprevention and.vaccine d.velopment. This review summarizes the current ad.ances regard.ng the roles of these markers in the management of PCa.

关键词： genetics management molecular prostate cancer

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THLAMO-CORTICAL SYSTEM OF NOCICEPTION IN ANIMALS

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神经解剖学杂志 2001年第B7期17卷 37-38页

作者： william d. WILLIS University of Texas Med.cal Branch Galveston Texas U.S.A. MD PhD

Imaging stud.es in human subjects ind.cate that several d.fferent regions of the cerebral cortex are activated.as a result of painful stimulation of the skin. Cortical processing occurs in the first and.second.somatosensory areas (SⅠ and.SⅡ), the anterior cingulate gyrus and.the insula. Nociceptive processing also occurs in subcortical structures, includ.ng the amygd.la, basal ganglia and.cerebellum. Sensory d.scrimination of pain appears

关键词：动物损伤感受大脑皮层疼痛刺激丘脑

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Emerging role of A-kinase anchoring protein 5 signaling in reward.circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： william J.Flerlage Mark L.d.ll’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed.Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA d.partment of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evid.nce supporting the hypothesis of synaptic d.sfunction as a major contributor to neural circuit and.network d.sruption und.rlying emotional and.mood.d.sregulation in psychiatric d.sord.rs(Simmons et al.,2024).d.verse sets of d.stinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and.synaptic plasticity in brain regions and.circuits through complex interactions organized.by numerous multivalent protein scaffold.,includ.ng the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

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Sublethal effects of subzero temperatures on the light brown apple moth, Epiphyas postvittana: fitness costs in response to partial freezing

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Insect Science 2019年第2期26卷 311-321页

作者： Amy C. Morey Robert C. Venette william d. Hutchison d.partment of Entomology University of Minnesota St. Paul Minnesota USA USd.. Forest Service Northern Research Station St. Paul Minnesota USA

Population responses to envir on mental extremes often d.ctate the bound. to species' d.stributions. However, population d.namics at, or near, those range limits may also be affected.by sublethal effects. We exposed.late instars and.pupae of an invasive leafroller, Epiphyaspostvittana (Walker)(Lepid.ptera: Tortricid.e), to cold.temperatures and.measured.the effects of exposure on subsequent survivorship, d.velopment, and.reprod.ction. Cold.temperature was applied.as acute exposure to -10 °C (a low, but not immed.ately lethal temperature for this species) or the onset of freezing (the peak of the supercooling point exotherm). Survival was d.fined.as the ability to successfully eclose as an ad.lt. We measured.immature d.velopment times, pupal mass, and.ad.lt longevity as proxies of fitness in survivors. Ad.itionally, surviving insects were mated.with ind.vid.als that had.not been exposed.to cold.to measure fertility. There was no d.fference between the proportion of larvae or pupae that survived.acute exposure to -10 °C and.those exposed.to the control temperature. Approximately 17% of larvae and.8% of pupae survived.brief period. with internal ice formation and.continued.d.velopment to become reprod.ctively viable ad.lts. Importantly, surviving the onset of freezing came with significant fitness costs but not to exposure to -10 °C;most insects that survived.partial freezing had.lower fertility and.shorter ad.lt lifespans than either the -10 °C or control group. These results are d.scussed.within the context of forecasting invasive in sect d.stributions.

关键词： fertility invasive species partial freeze tolerance supercooling point

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