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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

The efficacies and biomarker investigations of antiprogrammed death-1 (anti-PD-1)-based therapies for metastatic bone and soft tissue sarcoma

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Cancer Biology & Medicine 2022年第6期19卷 910-930页

作者： Jia Lu Ting Li Zhichao Liao Hui Yu Yongtian Zhao Haixiao Wu Zhiwu Ren Jun Zhao Ruwei Xing Sheng Teng Yun Yang Xiangchun Li Kexin Chen Jonathan Trent Jilong Yang Department of Bone and Soft Tissue Tumor Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Infection Management Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Key Laboratory of Molecular Cancer Epidemiology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China YuceBio Technology Co. Ltd.Shenzhen 518172China Department of Epidemiology and Biostatistics Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Sarcoma Multidisciplinary Program Sylvester Comprehensive Cancer CenterThe University of MiamiMiamiFL 33136USA

Objective:Sarcomas are a group of rare malignancies with various subtypes.Patients with metastatic sarcoma who have failed traditional treatments can possibly achieve better prognoses from using novel therapies,including anti-programmed death-1(PD-1)-based therapies.Methods:We retrospectively analyzed clinical data of 24 metastatic sarcoma patients from June 15,2016 to December 30,2019.These patients mainly received angiogenesis inhibitors combined with anti-PD-1 therapy after they became resistant to traditional treatments.Furthermore,8 patients underwent panel DNA and whole transcript sequencing.Results:Six patients received 2 cycles of anti-PD-1 therapy and were included in the safety evaluation only group.The median follow-up time was 5.77 months.The median progression-free survival was 7.59 months,the overall response rate was 16.7%and the disease control rate was 55.6%.Based on whole exome and transcript sequencing data,there was no association between TMB,TNB,MSI,HLA-LOH,and PD-L1 expressions and sarcoma types with clinical responses.Immunotherapy efficacy and bioinformatics analyses indicated higher intratumoral heterogeneity(ITH)in progressive disease(PD)patients and lower ITH in partial response(PR)and stable disease patients.A higher percentage of immune cell infiltration,especially monocytes,was observed in PR patients.Active stromal gene expression was increased in PD patients but decreased in PR patients.Enrichment analysis revealed that an increased TGF-βsignaling pathway was reversely correlated with anti-PD-1 efficacy,while a decreased inflammatory response signaling pathway was positively correlated with anti-PD-1 efficacy.Conclusions:Our study showed PD-1 inhibitors combined with anti-angiogenesis agents were effective and well-tolerated.ITH,monocyte ratio,stroma subtypes,and the status of immune-associated signaling pathways may be related with anti-PD-1 based therapy.

关键词： Sarcoma PD-1 PD-L1 immunotherapy angiogenesis safety efficacy biomarker

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 cancer and other solid tumors. This effort will be

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

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