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Abstract 2528: Rurality and neighborhood socioeconomic deprivation associated with patient-reported outcomes andsurvivalin men with prostate cancer in NRG RTOG 0415 在NRG RTOG 0415中,农村和社区社会经济剥夺与前列腺癌男性患者报告的预后和生存率相关
Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2528
J. Bai, S. Pugh, R. Eldridge, K. Yeager, Qi Zhang, W. Lee, A. B. Shah, I. Dayes, D. D'Souza, J. Michalski, J. Efstathiou, J. Longo, T. Pisansky, Jordan M. Maier, S. Faria, Anand Desai, S. Seaward, H. Sandler, M. Cooley, D. Bruner
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引用次数: 0
Abstract 2606: A nCounter-Based mRNA signature in plasma associates with localized non-small cell lung cancer 摘要:血浆中基于ncounter的mRNA信号与局限性非小细胞肺癌有关
Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2606
A. G. Capitán, J. Bracht, N. Potie, M. González-Cao, S. Viteri, A. Martínez-Bueno, C. Cabrera-Gálvez, P. Rubinstein, C. Mayo-de-las-Casas, J. Valarezo, chung-Ying Huang, C. Pedraz, Richard Boykind, S. Warren, R. Rosell, Miguel Ángel Molina-Vilaa, A. Aguilar-Hernández
Background: 80% of non-small cell lung cancer (NSCLC) cases are diagnosed at stages IIIB-IV and have a dismal prognosis with a median life expectancy that does not exceed 2 years. In contrast, patients diagnosed at early and locally advanced stages (I-IIIA) can undergo surgery and have the potential to be totally cured. Imaging technologies often detect lung nodules of unknown significance that pose a diagnostic challenge; some patients with benign nodules are submitted to unnecessary surgical interventions while others with small tumors are just kept in observation, risking a significant delay for treatment. A diagnostic test that could differentiate between benign and malignant masses would be of great help in this setting. Methods: Circulating-free RNA (cfRNA) was isolated from the plasma of healthy individuals (N=21), early(I-II) stage (N=22) and stage IIIA (N=12) NSCLC patients, using an automatic extraction method(Qiasymphony, Qiagen). Purified cfRNA was quantified using Qubit, retrotranscribed and pre-amplified (14cycles) using the Low RNA Input Amplification kit (NanoString Technologies). Gene expression analysis was performed on the nCounter platform using the PanCancer IO360TM (NanoString Technologies), which can detect 770 transcripts related to tumor biology, micro-environment and the immune system. Results: Gene expression analysis revealed differential patterns for some cf-mRNAs from localized stage NSCLC patients versus healthy controls. A bioinformatics recursive feature elimination algorithm selected a 16-gene mRNA signature that was able to distinguish between localized NSCLC and control samples with an area under the ROC curve of 0.91 to 0.95. Furthermore, the signature scores derived from the algorithm were significantly different between the two cohorts. Conclusions: We have found an 16-gene signature that can differentiate between cfRNA of localized stages NSCLC patients and control individuals. Our results warrant validation studies in larger cohorts. Citation Format: Ana Gimenez Capitan, Jillian Bracht, Nicolas Potie, Maria Gonzalez-Cao, Santiago Viteri, Alejandro Martinez-Bueno, Carlos Cabrera-Galvez, Pablo Rubinstein, Clara Mayo-de-las-Casas, Joselyn Valarezo, Chung-Ying Huang, Carlos Pedraz, Richard Boykind, Sarah Warren, Rafael Rosell, Miguel Angel Molina-Vilaa, Andres Aguilar-Hernandez. A nCounter-Based mRNA signature in plasma associates with localized non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2606.
背景:80%的非小细胞肺癌(NSCLC)病例诊断为iib - iv期,预后不佳,中位预期寿命不超过2年。相比之下,在早期和局部晚期(I-IIIA)诊断的患者可以接受手术,并有可能完全治愈。影像学技术经常检测到意义不明的肺结节,对诊断构成挑战;一些患有良性结节的患者接受了不必要的手术干预,而另一些患有小肿瘤的患者只是保持观察,这可能会严重延误治疗。在这种情况下,能够区分良性和恶性肿块的诊断测试将大有帮助。方法:采用Qiasymphony、Qiagen自动提取方法,从健康个体(N=21)、早期(I-II)期(N=22)和IIIA期(N=12) NSCLC患者血浆中分离游离循环RNA (cfRNA)。纯化的cfRNA使用量子比特进行定量,使用低RNA输入扩增试剂盒(NanoString Technologies)进行反转录和预扩增(14个周期)。在nCounter平台上使用PanCancer io360™(NanoString Technologies)进行基因表达分析,该平台可检测770个与肿瘤生物学、微环境和免疫系统相关的转录本。结果:基因表达分析揭示了局部分期NSCLC患者与健康对照者的一些cf- mrna的差异模式。生物信息学递归特征消除算法选择了一个16个基因的mRNA特征,该特征能够区分局部NSCLC和对照样本,ROC曲线下面积为0.91至0.95。此外,该算法得出的签名分数在两个队列之间存在显著差异。结论:我们发现了一个16个基因的特征,可以区分局部分期NSCLC患者和对照个体的cfRNA。我们的结果保证在更大的队列中进行验证研究。引文格式:Ana Gimenez Capitan、Jillian Bracht、Nicolas Potie、Maria Gonzalez-Cao、Santiago Viteri、Alejandro Martinez-Bueno、Carlos Cabrera-Galvez、Pablo Rubinstein、Clara Mayo-de-las-Casas、joseyn Valarezo、Chung-Ying Huang、Carlos Pedraz、Richard Boykind、Sarah Warren、Rafael Rosell、Miguel Angel Molina-Vilaa、Andres Aguilar-Hernandez。血浆中基于ncounter的mRNA信号与局限性非小细胞肺癌有关[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2606。
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引用次数: 0
Abstract 2546: Predictive value of prostate health index (PHI) in multi-parametric MRI in an ethnically diverse cohort 2546:前列腺健康指数(PHI)的多参数MRI在不同种族人群中的预测价值
Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2546
S. Carbunaru, R. Babajide, E. Schaeffer, P. Gann, Adam B. Murphy
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引用次数: 0
Abstract 2609: Hypoxia-mediated downregulation of GCNT2/I-antigen in metastatic melanoma accelerates disease progression and mortality 缺氧介导的GCNT2/ i抗原下调在转移性黑色素瘤中加速疾病进展和死亡率
Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2609
A. Chakraborty, M. Pérez, N. B. Mohammed, M. Wells, J. Wilmott, J. Thompson, S. Haslam, W. Wang, R. Scolyer, G. Murphy, C. Dimitroff
Metastatic melanoma is a lethal disease with a dismal 5-year survival rate. Thus, intense efforts to boost novel therapeutic strategies are underway to identify early detection of melanomas with a high propensity to metastasize. We recently discovered that the loss of cell surface glycan, I-antigen, corresponds with the transition of primary melanoma to metastatic melanoma. I-antigen or I-branched glycans are synthesized by β16, N-acetylglucosaminyltransferase 2 (GCNT2) and inversely correlate with the growth and signaling potential of metastatic melanoma cells. Moreover, compared with high GCNT2 expression in normal melanocytes, nevi, and early-stage primary melanomas, GCNT2 is conspicuously lost in metastatic melanomas. We anticipate the potential utilization of GCNT2 expression as a biomarker to predict melanoma metastasis. Further, metastasis and aggressive disease progression are key phenotypes of tumor-initiating cells (TIC), which are preferentially generated in areas of hypoxia. In the vertical growth phase of primary melanomas and melanoma metastases, the tumor microenvironment is typically hypoxic (1.5% oxygen). We hypothesize that the hypoxic microenvironment aids in metastatic melanoma progression through TIC generation and immune evasion, by downregulating GCNT2 and switching I-branched glycans to linear glycans. In this study, metastatic melanoma cells grown under hypoxic conditions had reduced GCNT2 and MITF with upregulated stem cell marker KLF4 expression. Importantly, in the in vivo TIC assay, we found significantly decreased tumor formation with increased GCNT2 expression while low GCNT2 levels enabled tumor formation even when 103 cells were injected in immunocompromised mice. Since TICs are thought to evade immune clearance, we investigated whether loss of GCNT2 increased TIC characteristics and also enabled immunosuppressive features. In human PBMC - metastatic melanoma co-cultures, there was an increase in T regulatory cell generation associated with low GCNT2 compared to high GCNT2 expression in melanoma cells, suggesting that loss of GCNT2 associates with increased TIC generation, tumor formation, and immunoevasion potential. Using melanoma patient specimens, immunohistochemical analysis of GCNT2 corresponded with a significant increase in mortality with the loss of GCNT2 staining. Altogether, these findings highlight GCNT2/I-branching not only as a biomarker of melanoma virulence but reveal malignancy-associated pathways functioning in parallel with loss of GCNT2/I-branching that could offer additional targets for the treatment of metastatic melanoma. Citation Format: Asmi Chakraborty, Mariana Perez, Norhan B. B Mohammed, Michael Wells, James S. Wilmott, John F. Thompson, Stuart M. Haslam, Wei Wang, Richard A. Scolyer, George F. Murphy, Charles J. Dimitroff. Hypoxia-mediated downregulation of GCNT2/I-antigen in metastatic melanoma accelerates disease progression and mortality [abstract]. In: Proceedings of the American A
转移性黑色素瘤是一种致命的疾病,5年生存率很低。因此,人们正在努力推动新的治疗策略,以识别具有高转移倾向的黑色素瘤的早期检测。我们最近发现,细胞表面聚糖,即i抗原的丧失,与原发性黑色素瘤向转移性黑色素瘤的转变相对应。i抗原或i支链聚糖由β16, n -乙酰氨基葡萄糖转移酶2 (GCNT2)合成,与转移性黑色素瘤细胞的生长和信号传导潜能呈负相关。此外,与GCNT2在正常黑色素细胞、痣和早期原发性黑色素瘤中的高表达相比,GCNT2在转移性黑色素瘤中明显缺失。我们期待GCNT2表达作为预测黑色素瘤转移的生物标志物的潜在应用。此外,转移和侵袭性疾病进展是肿瘤启动细胞(TIC)的关键表型,它们优先在缺氧区域产生。在原发性黑色素瘤和黑色素瘤转移的垂直生长阶段,肿瘤微环境通常为缺氧(1.5%氧气)。我们假设缺氧微环境通过TIC的产生和免疫逃避,通过下调GCNT2和将i支聚糖转换为线性聚糖,有助于转移性黑色素瘤的进展。在这项研究中,在缺氧条件下生长的转移性黑色素瘤细胞GCNT2和MITF减少,干细胞标记物KLF4表达上调。重要的是,在体内TIC实验中,我们发现GCNT2表达增加显著减少肿瘤形成,而低GCNT2水平即使在免疫功能低下的小鼠中注射103个细胞也能促进肿瘤形成。由于TIC被认为会逃避免疫清除,我们研究了GCNT2的缺失是否会增加TIC的特征,并激活免疫抑制特征。在人类PBMC -转移性黑色素瘤共培养中,与黑色素瘤细胞中GCNT2高表达相比,GCNT2低表达的T调节细胞生成增加,这表明GCNT2的缺失与TIC生成、肿瘤形成和免疫逃避潜力增加有关。使用黑色素瘤患者标本,GCNT2的免疫组织化学分析表明,随着GCNT2染色的丧失,死亡率显著增加。总之,这些发现强调了GCNT2/ i分支不仅是黑色素瘤毒力的生物标志物,而且揭示了与GCNT2/ i分支缺失并行的恶性相关通路,可以为转移性黑色素瘤的治疗提供额外的靶点。引文格式:Asmi Chakraborty, Mariana Perez, Norhan B. B. Mohammed, Michael Wells, James S. Wilmott, John F. Thompson, Stuart M. Haslam, Wang Wei, Richard A. Scolyer, George F. Murphy, Charles J. Dimitroff缺氧介导的GCNT2/ i抗原在转移性黑色素瘤中的下调加速了疾病进展和死亡率[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2609。
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引用次数: 0
Abstract 2602: Leveraging cell-free methylome markers for early cancer detection 2602:利用无细胞甲基组标记进行早期癌症检测
Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2602
Nicholas Cheng, Kimberly Skead, David Soave, Jocelyn Meng, Elias Gbeha, I. Lungu, Bernard Lam, S. Bratman, D. D. Carvalho, P. Awadalla
Cancer survival rates are significantly improved when detected at early stages, particularly when the tumor is still localized to the tissue of origin. However, effective screening tools for early cancer detection is currently limited to a subset of cancer types. The early development of human malignancies are difficult to observe as cancers are often detected once it becomes symptomatic, as such many cancer biomarker and evolution studies to date have primarily examined the genomics from solid tumor or liquid biopsies following a diagnosis. Investigating early tumor evolution in the pre-diagnosis context could allow us to better understand how to prevent or detect cancers in the earliest stage when survival rates are significantly higher, however this requires application of new technologies to biologics collected prior to a cancer diagnosis. Here, we leverage blood samples collected from participants in the Canadian Partnership for Tomorrow Project (CPTP), a longitudinal population cohort, prior to the onset of a cancer. Specifically, we utilize hybrid capture approaches to enrich for and characterize early mutations and methylation changes in circulating tumor DNA (ctDNA) of pre-cancer plasma samples collected from patients several months to years prior to clinical diagnosis. Here, we identify the earliest detectability of aberrant genetic and epigenetic events in ctDNA and describe the molecular evolution of these events at various stages prior to clinical detection of cancers. Further, we develop molecular biomarkers and implement machine learning tools to classify individuals with early cancers, and to develop risk scores from survival analyses predictive of cancer development up to 5 years prior to diagnosis. In our current study, we focus specifically on breast, prostate, lung and pancreatic cancer cases, and are extending this to pan-cancer applications in subsequent studies. Citation Format: Nicholas Cheng, Kimberly Skead, David Soave, Jocelyn Meng, Elias Gbeha, Ilinca Lungu, Bernard Lam, Scott Bratman, Daniel De Carvalho, Philip Awadalla. Leveraging cell-free methylome markers for early cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2602.
如果在早期阶段检测到癌症,特别是当肿瘤仍局限于原发组织时,癌症存活率显著提高。然而,有效的早期癌症检测工具目前仅限于癌症类型的一个子集。人类恶性肿瘤的早期发展很难观察到,因为癌症通常在出现症状时才被发现,因为迄今为止许多癌症生物标志物和进化研究主要是在诊断后检查实体肿瘤或液体活检的基因组学。在诊断前研究早期肿瘤进化可以让我们更好地了解如何在生存率显著提高的早期阶段预防或检测癌症,然而这需要将新技术应用于癌症诊断前收集的生物制剂。在这里,我们利用从加拿大明天合作项目(CPTP)参与者收集的血液样本,这是一个纵向人群队列,在癌症发病之前。具体而言,我们利用混合捕获方法来丰富和表征临床诊断前数月至数年从患者收集的癌前血浆样本中循环肿瘤DNA (ctDNA)的早期突变和甲基化变化。在这里,我们确定了ctDNA中异常遗传和表观遗传事件的最早可检测性,并描述了这些事件在癌症临床检测之前的各个阶段的分子进化。此外,我们开发分子生物标志物并实施机器学习工具来对早期癌症患者进行分类,并从生存分析中开发风险评分,预测癌症在诊断前5年的发展。在我们目前的研究中,我们专注于乳腺癌,前列腺癌,肺癌和胰腺癌病例,并在后续研究中将其扩展到泛癌症应用。引文格式:Nicholas Cheng, Kimberly Skead, David Soave, Jocelyn Meng, Elias Gbeha, Ilinca Lungu, Bernard Lam, Scott Bratman, Daniel De Carvalho, Philip Awadalla。利用无细胞甲基组标记物进行早期癌症检测[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2602。
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引用次数: 0
Abstract 2538: Retinol binding protein-1 and E6-E7 HR-HPV mRNA expression in normal cervical tissue and high grade squamous intraepithelial lesions 2538:视黄醇结合蛋白-1和E6-E7 HR-HPV mRNA在正常宫颈组织和高级别鳞状上皮内病变中的表达
Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2538
Ines Benedetti, Reinhard Rodríguez, Lía Barrios
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引用次数: 0
Abstract 2575: Intermittent calorie restriction reverses the adverse effects of obesity and advanced age on tumor growth in a mouse model of breast cancer 摘要:在乳腺癌小鼠模型中,间歇性卡路里限制逆转了肥胖和高龄对肿瘤生长的不利影响
Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2575
Dalton M. Craven, Laura A. Smith, Michael F. Coleman, Elaine M Glenny, S. Hursting
Advanced age and obesity are two major risk factors for breast cancer (BC) mortality. This presents a significant public health concern as the number of older individuals and incidence of obesity are increasing worldwide. In our mouse models of BC, we have demonstrated that, similar to obesity, advanced age accelerates mammary tumor growth. Mechanistically, obesity and advanced age suppress tumor gene expression relating to antitumor immunity and reduce tumoral abundance of cytotoxic CD8+ T cells. Thus, advanced age- and obesity-related enhancement of mammary tumor growth is explained, in part, through the development of an immunosuppressive tumor microenvironment. Given the aging of our populations and the increasing prevalence of obesity, interventions capable of reversing the tumor-promoting effects of advanced age and obesity are needed. We have previously demonstrated that weight loss by intermittent calorie restriction (ICR), in which mice are placed on a 5:2 calorie restriction (CR) regimen (5 days 14% CR, 2 nonconsecutive days 70% CR per week), attenuates tumor growth and immunosuppression in formerly obese mice. This project tests if ICR will provide similar benefit to aged and aged obese mice. Cohorts of young control (5 mos), young diet-induced obese (DIO; 5 mos), aged control (15 mos), and aged DIO (15 mos) mice were generated and subsequently randomized to either remain on their baseline diet or switch to the ICR intervention. Following 9 weeks on ICR or baseline diet, serum samples were collected and then tumor development induced by orthotopic transplantation of E0771 cancer cells into the 4th mammary fat pad of mice. At tumor endpoint mammary tumors were collected and weighed. To determine if ICR alters systemic inflammation in each experimental group, cytokine levels were measured in serum samples collected prior to tumor inoculation. Multiple inflammatory cytokines were downregulated following ICR intervention in young DIO, aged control, and aged DIO mice, including CCL7, CCL10, and CCL24. Downregulation of inflammatory cytokines was correlated with decreased tumor burden in young DIO, aged control, and aged DIO mice placed on ICR, compared with their respective non-intervention controls. Ongoing analyses are investigating if ICR increases the abundance of cytotoxic CD8+ T cells within the tumor microenvironment of young DIO, aged control, and aged DIO mice. These findings demonstrate that ICR may be effective in reversing obesity- and advanced age-related enhancement of mammary tumor growth in mouse models of breast cancer. More research is needed to test if these preclinical findings translate to obese and aged humans with BC. Identifying dietary interventions that may attenuate obesity- and age-related tumor growth has the potential to improve both patient outcomes and quality of life. This research was supported by R35CA197627 to S. Hursting. Citation Format: Dalton M. Craven, Laura A. Smith, Michael F. Coleman, Elaine M. Gl
高龄和肥胖是乳腺癌(BC)死亡的两个主要危险因素。这引起了一个重大的公共卫生问题,因为世界范围内老年人的数量和肥胖的发病率都在增加。在我们的小鼠BC模型中,我们已经证明,与肥胖相似,高龄会加速乳腺肿瘤的生长。机制上,肥胖和高龄抑制肿瘤抗肿瘤免疫相关基因的表达,降低肿瘤细胞毒性CD8+ T细胞的丰度。因此,高龄和肥胖相关的乳腺肿瘤生长增强部分是通过免疫抑制肿瘤微环境的发展来解释的。考虑到人口老龄化和肥胖的日益流行,需要能够逆转高龄和肥胖对肿瘤促进作用的干预措施。我们之前已经证明,通过间歇性卡路里限制(ICR)减肥,小鼠被放置在5:2的卡路里限制(CR)方案中(每周5天14% CR,非连续2天70% CR),减轻了以前肥胖小鼠的肿瘤生长和免疫抑制。该项目测试ICR是否会对老年和老年肥胖小鼠提供类似的益处。年轻对照组(5个),年轻饮食诱导肥胖(DIO;生成5只(只)、15只(只)老年对照小鼠和15只(只)老年DIO小鼠,随后随机分为两组,一组保持基线饮食,另一组改用ICR干预。在ICR或基线饮食9周后,采集血清样本,然后将E0771癌细胞原位移植到小鼠第4乳腺脂肪垫诱导肿瘤发展。在肿瘤终点收集乳腺肿瘤并称重。为了确定ICR是否改变了每个实验组的全身性炎症,在肿瘤接种前收集的血清样本中测量了细胞因子水平。包括CCL7、CCL10和CCL24在内的年轻DIO、老年对照组和老年DIO小鼠,在ICR干预后,多种炎症细胞因子下调。与各自的非干预对照组相比,接受ICR治疗的年轻DIO小鼠、老年对照组小鼠和老年DIO小鼠的炎症细胞因子下调与肿瘤负荷降低相关。正在进行的分析正在调查ICR是否会增加年轻DIO小鼠、老年对照小鼠和老年DIO小鼠肿瘤微环境中细胞毒性CD8+ T细胞的丰度。这些发现表明,在乳腺癌小鼠模型中,ICR可能有效逆转肥胖和高龄相关的乳腺肿瘤生长增强。需要更多的研究来验证这些临床前研究结果是否适用于肥胖和老年BC患者。确定饮食干预可能减轻肥胖和年龄相关肿瘤的生长,有可能改善患者的预后和生活质量。本研究得到了R35CA197627 to S. Hursting的支持。引文格式:Dalton M. Craven, Laura A. Smith, Michael F. Coleman, Elaine M. Glenny, Stephen D. Hursting。在乳腺癌小鼠模型中,间歇性卡路里限制逆转了肥胖和高龄对肿瘤生长的不利影响[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2575。
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引用次数: 0
Abstract LB221: Randomized crossover trial evaluating detoxication of tobacco carcinogens by broccoli seed and sprout extract in heavy smokers 摘要LB221:评价重度吸烟者西兰花籽和芽提取物对烟草致癌物解毒作用的随机交叉试验
Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-LB221
J. Bauman, Chiu-Hsieh Hsu, Sara M Centuori, José M. Guillén-Rodríguez, L. Garland, E. Ho, Lisa Bengtson, M. Wojtowicz, É. Szabó, H. Chow
Randomized crossover trial evaluating detoxication of tobacco carcinogens by broccoli seed and sprout extract in heavy smokersJulie E. Bauman, Chiu-Hsieh Hsu, Sara Centuori, Jose Guillen-Rodriguez, Linda Garland, Emily Ho, Lisa Bengtson, Malgorzata Wojtowicz, Eva Szabo, H-H Sherry ChowIntroduction: Diets high in cruciferous vegetables are associated with reduced risk of tobacco-related cancers. Crucifers are rich in the phytochemical glucoraphanin (GR), which is hydrolyzed by myrosinase to its bioactive form, sulforaphane (SF). SF upregulates the NRF2 transcription factor and downstream target genes in the antioxidant response element. As GR is concentrated in broccoli seeds relative to mature plants, broccoli seed preparations (BSP) are under development as chemopreventive agents. BSP increased detoxication of air pollutants including benzene in Qidong, China. Methods: We conducted a randomized crossover trial evaluating the detoxication of benzene and other tobacco carcinogens by the BSP Avmacol, tablets comprised of broccoli seed powder and broccoli sprout extract, in otherwise healthy smokers (≥ 20 pack-years). Each subject was treated with low and high dose BSP (70 vs. 140 GR equivalents daily for 2 weeks), separated by a 2-week washout, with randomization to low-high vs. high-low sequence. The primary endpoint was detoxication of benzene, measured by change in urinary excretion of its mercapturic acid metabolite (S-phenyl mercapturic acid, SPMA). Secondary endpoints included detoxication of the carcinogens acrolein and crotonaldehyde, and SF bioavailability assessed by urinary SF metabolites.Results: 49 subjects were randomized from Feb 2018-Nov 2019: 26 female, mean age 56.3. Treatment-related adverse events (AE) were gastrointestinal; most common were grade 1-2 bloating/cramping/abdominal pain (11; 22%), grade 1 diarrhea (11; 22%), grade 1 flatulence (10; 20%). No grade ≥ 3 AE were observed. One subject withdrew after unrelated AE. Compliance with BSP and biomarker measurements was 98%. Primary and secondary endpoints are presented in the Table. Conclusion: The BSP Avmacol was bioavailable as SF metabolites and significantly increased the acute detoxication products of benzene and acrolein in heavy smokers. Citation Format: Julie E. Bauman, Chiu-Hsieh Hsu, Sara Centuori, Jose Guillen-Rodriguez, Linda Garland, Emily Ho, Lisa Bengtson, Malgorzata Wojtowicz, Eva Szabo, H-H Sherry Chow. Randomized crossover trial evaluating detoxication of tobacco carcinogens by broccoli seed and sprout extract in heavy smokers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB221.
julie E. Bauman, chu - hsieh Hsu, Sara Centuori, Jose Guillen-Rodriguez, Linda Garland, Emily Ho, Lisa Bengtson, Malgorzata Wojtowicz, Eva Szabo, H-H Sherry cho温介绍:多吃十字花科蔬菜可以降低患烟草相关癌症的风险。十字花科植物富含植物化学物质葡萄糖苷(GR),经黑芥子酶水解成其生物活性形式萝卜硫素(SF)。SF上调抗氧化反应元件中的NRF2转录因子和下游靶基因。由于相对于成熟植物,GR主要集中在西兰花种子中,因此西兰花种子制剂(BSP)作为化学预防剂正在开发中。BSP增加了中国启东包括苯在内的空气污染物的解毒。方法:我们在健康吸烟者(≥20包年)中进行了一项随机交叉试验,评估由西兰花籽粉和西兰花芽提取物组成的BSP Avmacol片对苯和其他烟草致癌物的解毒作用。每个受试者接受低剂量和高剂量BSP治疗(每天70和140 GR当量,持续2周),通过2周的洗脱期分开,随机分为低-高和高-低顺序。主要终点是苯的解毒,通过尿中苯的硫化氢代谢物(s -苯基硫化氢,SPMA)的排泄变化来测量。次要终点包括致癌物丙烯醛和巴豆醛的解毒作用,以及通过尿中SF代谢物评估SF的生物利用度。结果:49名受试者于2018年2月- 2019年11月随机纳入:女性26名,平均年龄56.3岁。治疗相关不良事件(AE)为胃肠道;最常见的是1-2级腹胀/痉挛/腹痛(11;22%), 1级腹泻(11;22%), 1级肠胃胀气(10;20%)。没有观察到≥3级AE。一名受试者因无关AE退出。BSP和生物标志物测量的依从性为98%。主要和次要终点列于表中。结论:BSP Avmacol作为SF代谢物具有生物利用性,可显著提高重度吸烟者苯和丙烯醛的急性解毒产物。引用格式:Julie E. Bauman, chu - hsieh Hsu, Sara Centuori, Jose Guillen-Rodriguez, Linda Garland, Emily Ho, Lisa Bengtson, Malgorzata Wojtowicz, Eva Szabo, H-H Sherry Chow。重度吸烟者西兰花籽和芽提取物对烟草致癌物解毒作用的随机交叉试验[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):摘要nr LB221。
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引用次数: 0
Abstract 2574: Collagen density and obesity promote mammary gland inflammation 摘要:胶原蛋白密度和肥胖促进乳腺炎症
Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2574
Abbey E Williams, E. Hoffman, J. Warren, S. Ponik, Lisa M. Arendt
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引用次数: 0
Abstract 2604: Urinary microRNAs as biomarkers for early detection of urothelial cancer 摘要2604:尿微rna作为尿路上皮癌早期检测的生物标志物
Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-2604
Kazuya Takayama, Kohei Yamazaki, H. Yamaguchi, Keishu Tsuda, T. Yasui, Y. Ichikawa
microRNAs modulate gene expression in various cancer types, and their profiles differ in healthy and cancer groups of people and they represent a warning sign for various cancer scenarios. Identification of tumor-specific microRNAs presents a powerful opportunity to potentially reduce cancer mortality through early detection. In order to achieve early detection through population screening, noninvasive approaches are needed to complement and improve upon current strategies for urothelial cancer (UC) screening. Since all microRNAs in the blood cannot be transferred from donor to recipient cells during single blood circulation, kidney filtration could pass some untransferred microRNAs from blood to urine, therefore urinary microRNAs might be used as biomarkers for the diagnosis of cancer. We investigated whether urine levels of microRNA can differentiate patients with UC from healthy individuals. Here, we successfully identified UC-related microRNA ensembles in urine through a combination of microfluidic microRNA extraction device and machine learning-based analysis. We analyzed 93 urine samples from 27 UC patients and 66 healthy individuals (controls). An initial set of 74 microRNAs was selected by microarray microRNA profiling assay as biomarker candidates. Quantitative reverse-transcription PCR was used for further analysis to validate the expression of microRNAs. We selected a group of 6 microRNAs for validation; (miR-6089, miR-4488, miR-4784, miR-26a-5p, miR-148a-3p, and miR-143-3p) were confirmed to be significantly different in UC and controls. We adopted a logistic regression model and successfully developed a classifier based on these 6 microRNAs, which showed remarkably high sensitivity (94%) and specificity (85%). In summary, patients with UC have significantly different patterns of microRNA expression from healthy individuals. We identified a signature of 6 microRNAs as predictors that can differentiate patients with UC from those who are healthy. These microRNAs could be potentially developed as biomarkers for UC. Citation Format: Kazuya Takayama, Kohei Yamazaki, Hiroki Yamaguchi, Keishu Tsuda, Takao Yasui, Yuki Ichikawa. Urinary microRNAs as biomarkers for early detection of urothelial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2604.
microrna调节各种癌症类型的基因表达,它们的特征在健康人群和癌症人群中有所不同,它们代表了各种癌症情景的警告信号。肿瘤特异性microrna的鉴定为通过早期检测潜在地降低癌症死亡率提供了一个强大的机会。为了通过人群筛查实现早期发现,需要非侵入性方法来补充和改进当前的尿路上皮癌(UC)筛查策略。由于血液中的所有microrna不能在单次血液循环中从供体细胞转移到受体细胞,肾脏过滤可以将一些未转移的microrna从血液传递到尿液,因此尿液中的microrna可能用作癌症诊断的生物标志物。我们研究了尿中microRNA水平是否可以区分UC患者和健康人。在这里,我们通过微流控microRNA提取装置和基于机器学习的分析相结合,成功地鉴定了尿中uc相关的microRNA集合。我们分析了来自27名UC患者和66名健康个体(对照组)的93份尿液样本。通过微阵列分析筛选出74个microRNA作为候选生物标志物。采用定量反转录PCR进一步分析验证microrna的表达。我们选择了一组6个microrna进行验证;(miR-6089, miR-4488, miR-4784, miR-26a-5p, miR-148a-3p和miR-143-3p)在UC和对照组中被证实存在显著差异。我们采用逻辑回归模型,成功开发了基于这6个microrna的分类器,该分类器具有非常高的灵敏度(94%)和特异性(85%)。总之,UC患者的microRNA表达模式与健康个体明显不同。我们确定了6个microrna作为区分UC患者和健康患者的预测因子。这些microrna可能被开发为UC的生物标志物。引文格式:Kazuya Takayama, Kohei Yamazaki, Hiroki Yamaguchi, Keishu Tsuda, Takao Yasui, Yuki Ichikawa。尿微rna作为尿路上皮癌早期检测的生物标志物[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2604。
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Prevention Research
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