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Gastrointestinal stromal tumor and its targeted therapeutics

Chinese Journal of Cancer 2011年第5期30卷 303-314页

作者： Jheri Dupart jonathan C.trent Departments of Sarcoma Medical Oncology and Pathology The University of Texas MD Anderson Cancer Center

Over the past 60 years,investigators of basic science,pathology,and clinical medicine have studied gastrointestinal stromal tumor(GIST) and made minor advances in patient *** discoveries have led to an understanding of the biological role of KIT and platelet-derived growth factor receptor-α in GIST and the development of the tyrosine kinase inhibitor imatinib mesylate(Gleevec,formerly STI-571),one of the most exciting examples of targeted therapy to *** success of targeted therapy in GIST has lead to new developments in our understanding of the medical and surgical management of the *** study of GIST may lead to new paradigms in the management of cancer.

关键词：靶向治疗胃肠道间质血小板衍生生长因子酪氨酸激酶抑制剂生物学作用基础科学临床医学

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The favorable impact of PIK3CA mutations on survival: an analysis of 2587 patients with breast cancer

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Chinese Journal of Cancer 2012年第7期31卷 327-334页

作者： Amaury G. Dumont Sarah N.Dumont jonathan C. trent Department of Experimental Pediatrics University of Texas-MD Anderson Cancer CenterHouston Texas United States Division of Hematology and Oncology University of Miami-Sylvester Comprehensive Cancer CenterMiami Florida United States

The phosphatidylinositol-3 kinase(PI3K) pathway regulates a number of cellular processes, including cell survival, cell growth, and cell cycle progression. Consequently, this pathway is commonly deregulated in cancer. In particular, mutations in the gene PIK3CA that encodes the p110α catalytic subunit of the PI3K enzymes result in cell proliferation and resistance to apoptosis in vitro and induce breast tumors in transgenic mice. These data underscore the role of this pathway during oncogenesis. Thus, an ongoing, large-scale effort is underway to develop clinically active drugs that target elements of the PI3K pathway. However, conflicting data suggest that gain-of-function PIK3CA mutations may be associated with either a favorable or a poor clinical outcome, compared with the wild-type PIK3CA gene. In the current study, we performed a systematic review of breast cancer clinical studies. Upon evaluation of 2587 breast cancer cases from 12 independent studies, we showed that patients with tumors harboring a PIK3CA mutation have a better clinical outcome than those with a wild-type PIK3CA gene. Importantly, this improved prognosis may pertain only to patients with mutations in the kinase domain of p110α and to postmenopausal women with estrogen receptor-positive breast cancer. We propose three potential explanations for this paradoxical observation. First, PIK3CA mutations may interfere with the metastasis process or may induce senescence, which results in a better outcome for patients with mutated tumors. Secondly, we speculate that PIK3CA mutations may increase early tumor diagnosis by modification of the actin cytoskeleton in tumor cells. Lastly, we propose that PIK3CA mutations may be a favorable predictive factor for response to hormonal therapy, giving a therapeutic advantage to these patients. Ultimately, an improved understanding of the clinical impact of PIK3CA mutations is critical for the development of optimally personalized therapeutics against breast can

关键词：肿瘤患者乳腺癌突变转基因小鼠肌动蛋白细胞骨架磷脂酰肌醇-3 信号通路乳腺肿瘤

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平滑肌肉瘤中PRUNE2mRNA的表达及其与非编码RNAPCA3的一致性关系

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中华肿瘤杂志 2012年第7期34卷 497-500页

作者：杨吉龙 David Cogdell James Eddy jonathan trent Nathan Price ZHANG Wei 天津医科大学附属肿瘤医院骨与软组织肿瘤科 300060

目的探讨平滑肌肉瘤中PRUNE2mRNA的表达及其与非编码RNAPCA3的关系。方法采用安捷伦基凶表达芯片的方法检测31例平滑肌肉瘤和42例胃肠间质瘤中PRUNE2mRNA的表达水平，分析其表达与平滑肌肉瘤患者的预后关系；采用实时荧光定量聚合酶链... 详细信息

目的探讨平滑肌肉瘤中PRUNE2mRNA的表达及其与非编码RNAPCA3的关系。方法采用安捷伦基凶表达芯片的方法检测31例平滑肌肉瘤和42例胃肠间质瘤中PRUNE2mRNA的表达水平，分析其表达与平滑肌肉瘤患者的预后关系；采用实时荧光定量聚合酶链反应的方法分析13例平滑肌肉瘤中PCA3mRNA和PRUNE2mRNA的表达水平并分析二者间的关系。7例前列腺癌组织作为PCA3mRNA表达的阳性对照。结果在31例平滑肌肉瘤中，PRUNE2mRNA的平均表达水平为368．43±29．67，高于37例胃肠间质瘤（82．56±7．45）和7例前列腺癌（4．76±0．98，均P〈0．05）。PRUNE2mRNA高表达的平滑肌肉瘤患者的生存期与低表达者比较，差异无统计学意义（X2=0．96，P=0．326）。PRUNE2mRNA高表达的胃肠间质瘤患者的生存期与低表达者比较，差异无统计学意义（X2=3．10，P=0．078）。平滑肌肉瘤中PcA3mRNA平均表达水平为26．38±3．04，低于前列腺癌（3272．00±240．87，P=0．004）。在平滑肌肉瘤中，PCA3mRNA与PRUNE2mRNA的表达呈正相关（r=0．901，P〈0．001）。结论PRUNE2的表达与平滑肌肉瘤患者的生存期有关，PCA3的表达与PRUNE2mRNA的表达呈正相关。

关键词：平滑肌肉瘤 RNA,未翻译 PRUNE2 PCA3 预后

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Microalgae Cultivation Using Offshore Membrane Enclosures for Growing Algae (OMEGA)

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Journal of Sustainable Bioenergy Systems 2013年第1期3卷 18-32页

作者： Patrick Wiley Linden Harris Sigrid Reinsch Sasha Tozzi Tsegereda Embaye Kit Clark Brandi McKuin Zbigniew Kolber Russel Adams Hiromi Kagawa Tra-My Justine Richardson John Malinowski Colin Beal Matthew A. Claxton Emil Geiger Jon Rask J. Elliot Campbell jonathan D. trent Advanced Organic Methods Penryn USA Department of Chemistry University of California Santa Cruz USA Department of Mechanical Engineering University of Nevada Reno USA Department of Ocean Sciences University of California Santa Cruz USA Dynamac Corporation NASA Ames Research Center Moffett Field USA NASA Ames Research Center Moffett Field USA School of Engineering University of California Merced USA SETI Institute Mountain View USA Universities Space Research Association Columbia USA

OMEGA is a system for cultivating microalgae using wastewater contained in floating photobioreactors (PBRs) deployed in marine environments and thereby eliminating competition with agriculture for water, fertilizer, and land. The offshore placement in protected bays near coastal cities co-locates OMEGA with wastewater outfalls and sources of CO2-rich flue gas on shore. To evaluate the feasibility of OMEGA, microalgae were grown on secondary-treated wastewater supplemented with simulated flue gas (8.5% CO2 V/V) in a 110-liter prototype system tested using a seawater tank. The flow-through system consisted of tubular PBRs made of transparent linear low-density polyethylene, a gas exchange and harvesting column (GEHC), two pumps, and an instrumentation and control (I&C) system. The PBRs contained regularly spaced swirl vanes to create helical flow and mixing for the circulating culture. About 5% of the culture volume was continuously diverted through the GEHC to manage dissolved oxygen concentrations, provide supplemental CO2, harvest microalgae from a settling chamber, and add fresh wastewater to replenish nutrients. The I&C system controlled CO2 injection and recorded dissolved oxygen levels, totalized CO2 flow, temperature, circulation rates, photosynthetic active radiation (PAR), and the photosynthetic efficiency as determined by fast repetition rate fluorometry. In two experimental trials, totaling 23 days in April and May 2012, microalgae productivity averaged 14.1 ± 1.3 grams of dry biomass per square meter of PBR surface area per day (n = 16), supplemental CO2 was converted to biomass with >50% efficiency, and >90% of the ammonia-nitrogen was recovered from secondary effluent. If OMEGA can be optimized for energy efficiency and scaled up economically, it has the potential to contribute significantly to biofuels production and wastewater treatment.

关键词： Biofuels Wastewater Treatment Microalgae Photobioreactor CO2 Mass Transfer Fast Repetition Rate Fluorometry Instrumentation and Control

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Skin 11β-hydroxysteroid dehydrogenase type 1 enzyme expression regulates burn wound healing and can be targeted to modify scar characteristics

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Burns & Trauma 2023年第1期11卷 32-45页

作者： Kevin H.-Y.Tsai Huaikai Shi Roxanne J.Parungao Sina Naficy Xiaotong Ding Xiaofeng Ding jonathan J.Hew Xiaosuo Wang Wojciech Chrzanowski Gareth G.Lavery Zhe Li Andrea C.Issler-Fisher Jun Chen Qian Tan Peter K.Maitz Mark S.Cooper Yiwei Wang Adrenal Steroid Group ANZAC Research InstituteConcord HospitalThe University of SydneySydneyNSW 2137Australia Burns and Reconstructive Surgery Research Group ANZAC Research InstituteConcord HospitalThe Uni-versity of SydneySydneyNSW 2137Australia School of Chemical and Biomolecular Engineering The University of SydneySydneyNSW 2006Australia Jiangsu Provincial Engineering Research Centre of TCM External Medication Development and Application Nanjing University of Chinese MedicineNanjingJiangsu210023China Department of Burns and Plastic Surgery Nanjing Drum Tower Hospital Clinical CollegeNanjing University of Chinese MedicineNanjingJiangsu210008China Heart Research Institute The University of SydneySydneyNSW 2006Australia Sydney Nano Institute Sydney Pharmacy SchoolFaculty of Medicine and HealthThe University of SydneySydneyNSW2006Australia Department of Biosciences Centre for Healthy Ageing and Understanding DiseaseNottingham Trent UniversityNG14BUUK Burns and Reconstructive Surgery Unit Concord Repatriation General HospitalSydneyNSW 2137Australia

Background:Excessive scarring and fibrosis are the most severe and common complications of burn *** exposure to high levels of glucocorticoids detrimentally impacts on skin,leading to skin thinning and impaired wound *** can generate active glucocorticoids locally through expression and activity of the 11β-hydroxysteroid dehydrogenase type 1 enzyme(11β-HSD1).We hypothesised that burn injury would induce 11β-HSD1 expression and local glucocorticoid metabolism,which would have important impacts on wound healing,fibrosis and *** additionally proposed that pharmacological manipulation of this system could improve aspects of post-burn ***:Skin 11β-HSD1 expression in burns patients and mice was *** impacts of 11β-HSD1 mediating glucocorticoid metabolism on burn wound healing,scar formation and scar elas-ticity and quality were additionally examined using a murine 11β-HSD1 genetic knockout ***-release scaffolds containing therapeutic agents,including active and inactive glucocorticoids,were developed and pre-clinically tested in mice with burn ***:We demonstrate that 11β-HSD1 expression levels increased substantially in both human and mouse skin after burn injury.11β-HSD1 knockout mice experienced faster wound healing than wild type mice but the healed wounds manifested significantly more collagen deposition,tensile strength and stiffness,features characteristic of excessive *** of slow-release prednisone,an inactive glucocorticoid,slowed the initial rate of wound closure but significantly reduced post-burn scarring via reductions in inflammation,myofibroblast generation,collagen production and scar ***:Skin 11β-HSD1 expression is a key regulator of wound healing and scarring after burn *** of an inactive glucocorticoid capable of activation by local 11β-HSD1 in skin slows the initial rate of wound closure but significantlyimproves scar characteristics po

关键词： Wound healing Burn injury Scarring Skin 11β-HSD1 11β-HSD1 knockout Glucocorticoid metabolism Polycaprolactone scaffold Drug delivery

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