vimentin

Patent covers proprietary method using methylation of the CCNA1 gene to help detect esophageal precancer and cancer NEW YORK, Oct. 15, 2024 /PRNewswire/ -- Lucid Diagnostics Inc. (Nasdaq: LUCD) ("Lucid" or the "Company"), a commercial-stage, cancer prevention medical diagnostics company, and subsidiary of PAVmed Inc. (Nasdaq: PAVM), today announced that it has received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for a patent application covering its proprietary method of using methylation of the cyclin-A1 (CCNA1) gene to help detect esophageal precancer and cancer, a key component of its EsoGuard® Esophageal DNA Test. "This patent strengthens the already robust intellectual property portfolio underlying our groundbreaking technologies and will provide strong protection for the CCNA1 methylation assay method which is at the heart of the EsoGuard assay," said Lishan Aklog, M.D., Lucid's Chairman and Chief Executive Officer. "The allowance validates our strategy of focusing on the laboratory methods of our assay—a strategy we will continue to aggressively pursue for other components of the assay." EsoGuard utilizes next-generation sequencing (NGS) to assess DNA methylation at 31 sites on two genes, vimentin (VIM) and cyclin-A1 (CCNA1). Such methylation has been shown to be strongly associated with conditions along the spectrum from early esophageal precancer (non-dysplastic Barrett's Esophagus or BE), to late precancer (dysplastic BE), to cancer (esophageal adenocarcinoma). Although VIM methylation had been previously associated with gastrointestinal neoplasias, the association of CCNA1 methylation with esophageal neoplasia is novel and appears to be more specific. The technology behind EsoGuard and the EsoCheck® Esophageal Cell Collection Device was developed at Case Western Reserve University (CWRU) by faculty members Sanford Markowitz, M.D., PhD, Amitabh Chak, M.D., and Joseph Willis, M.D., with the support of research funds from the National Institutes of Health (NIH) and elsewhere. Lucid holds the exclusive worldwide license to commercialize this technology. The successful transfer of the assay from the academic research laboratory and its subsequent commercialization was the result of close, ongoing collaboration between Lucid and CWRU. About Lucid Diagnostics Lucid Diagnostics Inc. is a commercial-stage, cancer prevention medical diagnostics company and subsidiary of PAVmed Inc. (Nasdaq: PAVM). Lucid is focused on the millions of patients with gastroesophageal reflux disease (GERD), also known as chronic heartburn, who are at risk of developing esophageal precancer and cancer. Lucid's EsoGuard® Esophageal DNA Test, performed on samples collected in a brief, noninvasive office procedure with its EsoCheck® Esophageal Cell Collection Device, represent the first and only commercially available tools designed with the goal of preventing cancer and cancer deaths through widespread, early detection of esophageal precancer in at-risk patients. For more information about Lucid, please visit and for more information about its parent company PAVmed, please visit . Forward-Looking Statements This press release includes forward-looking statements that involve risk and uncertainties. Forward-looking statements are any statements that are not historical facts. Such forward-looking statements, which are based upon the current beliefs and expectations of Lucid's management, are subject to risks and uncertainties, which could cause actual results to differ from the forward-looking statements. Risks and uncertainties that may cause such differences include, among other things, volatility in the price of Lucid's common stock; general economic and market conditions; the uncertainties inherent in research and development, including the cost and time required to advance Lucid's products to regulatory submission; whether regulatory authorities will be satisfied with the design of and results from Lucid's clinical and preclinical studies; whether and when Lucid's products are cleared by regulatory authorities; market acceptance of Lucid's products once cleared and commercialized; Lucid's ability to raise additional funding as needed; and other competitive developments. In addition, Lucid continues to monitor the COVID-19 pandemic and the pandemic's impact on Lucid's businesses. These factors are difficult or impossible to predict accurately and many of them are beyond Lucid's control. In addition, new risks and uncertainties may arise from time to time and are difficult to predict. For a further list and description of these and other important risks and uncertainties that may affect Lucid's future operations, see Part I, Item 1A, "Risk Factors," in Lucid's most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, as the same may be updated in Part II, Item 1A, "Risk Factors" in any Quarterly Report on Form 10-Q filed by Lucid Diagnostics after its most recent Annual Report. Lucid disclaims any intention or obligation to publicly update or revise any forward-looking statement to reflect any change in its expectations or in events, conditions, or circumstances on which those expectations may be based, or that may affect the likelihood that actual results will differ from those contained in the forward-looking statements. 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【导读】 肿瘤微环境中的间充质干细胞（MSCs）对于癌症的发生、发展和转移至关重要。MSCs对膀胱癌的影响及其机制尚不明确。 近日，兰州大学与布朗大学研究人员合作在期刊《Cell Death&Disease》上发表了研究论文，题为“Mesenchymal stem cells in tumor microenvironment: drivers of bladder cancer progression through mitochondrial dynamics and energy production”，本研究中，研究人员分析了205例患者样本，以探讨肿瘤-间质比与临床病理特征之间的关系。通过使用共培养模型和裸鼠移植模型来探索间充质干细胞对膀胱癌细胞的生物学作用和分子机制。研究人员发现，较高的肿瘤-间质比与较大的肿瘤体积和较高的T分期、病理分级、血管浸润数量以及较差的总体生存率显著相关。TME中的间充质干细胞促进膀胱癌细胞在体外和体内的增殖、迁移和侵袭能力。接下来，研究人员证明间充质干细胞增强膀胱癌细胞的线粒体自噬和线粒体生成，增加能量产生，从而促进膀胱癌细胞进展。间充质干细胞产生的色氨酸（Kyn）通过激活AMPK通路增强线粒体功能。IDO1抑制剂可以在体外和体内逆转间充质干细胞的促肿瘤作用。 本研究结果表明，TME中间充质干细胞产生的色氨酸可以通过激活AMPK通路增强线粒体功能，从而促进膀胱癌细胞进展。 https://www-nature-com.libproxy1.nus.edu.sg/articles/s41419-024-07068-9 背景知识 01 膀胱癌（BC）在全球男性和女性中均是第10大常见癌症，2020年估计有57.3万例新病例和12.0万例死亡病例。当BC进展到肌层浸润阶段时，患者的预后通常较差。肿瘤微环境（TME）由恶性和非恶性细胞组成，当前的研究主要集中在恶性上皮细胞的遗传和表观遗传改变上。然而，尽管间质细胞影响癌症进展并影响对治疗的反应，但它们仍相对未被深入研究。因此，有必要探索TME中非恶性细胞对BC的影响，并开发一种新的治疗策略来靶向这些相互作用。 间充质干细胞（MSCs）具有在多种肿瘤类型中向肿瘤迁移的能力，并对肿瘤的进程产生重大影响。此外，有证据表明，MSC存在于人类膀胱和尿液中。虽然一些研究表明MSC可以加速肿瘤的生长，但另一些研究则认为它们具有抗肿瘤特性。MSC对BC的具体影响和机制仍需进一步研究，应开发新的治疗策略，以靶向MSC治疗BC。 恶性细胞与非恶性细胞之间的竞争与相互作用是肿瘤细胞代谢重编程的关键因素，这对癌症的启动、增殖和进展至关重要。线粒体是细胞能量代谢的中心，对癌症的多个方面产生显著影响，包括促进肿瘤合成、调节还原态和钙稳态、参与转录调控以及控制细胞死亡，从而影响癌症的发生、生长、存活和转移。尚不清楚MSC是否能调节线粒体代谢来影响癌症的行为。 MSCs在体外和体内都能促进膀胱癌细胞增殖 02 为了评估MSC在体外BC进展中的生物学意义，研究人员选择了UMUC-3和T24细胞与MSC共同培养在迁移共培养板中。结果显示，MSC共培养后，BC细胞的克隆形成、EdU、伤口愈合和迁移试验均显示出显著的增殖、迁移和侵袭能力增强（所有p<0.05）。随后，研究人员采用蛋白质免疫印迹实验分析来研究上皮间质转化（EMT）相关因子（N-cadherin、E-cadherin和Vimentin）的表达模式。结果显示，与MSC共培养后，N-cadherin和Vimentin的表达增加，而E-cadherin的表达降低。这些结果共同表明，MSC增加了BC细胞的增殖、迁移和侵袭能力。此外，研究人员从BC患者组织中分离出MSC（p-MSCs），并采用先前建立的分选策略对其分化潜能进行了评估。在特定的诱导条件下，p-MSCs能够分化为成骨、软骨和脂肪细胞。克隆形成试验显示，来自两名患者的p-MSCs可以促进膀胱癌细胞的增殖。 图1：MSCs在体外和体内都能促进膀胱癌细胞的增殖 为了评估MSC对人BC肿瘤发生的影响及肿瘤生长的影响，研究人员采用雌性无胸腺小鼠进行UMUC-3细胞异种移植研究。动物治疗时间线如图1f所示。如图1g所示，共注射组的肿瘤形成时间较对照组短。在肿瘤形成后，共注射组和MSC组在不同时间点上的肿瘤生长速度显著快于对照组。实验结束时，共注射组和MSC组的肿瘤净重较对照组增加。 IDO1抑制剂可以在体外和体内逆转MSCs的促肿瘤作用 03 MSCs 被施以不同浓度的 IDO1 抑制剂（IDO1i）处理24 小时，研究人员观察到随着IDO1i浓度的增加，MSCs中IDO1的表达显著降低。接下来，研究人员评估了IDO1抑制剂是否可以逆转MSCs的促肿瘤作用。克隆形成试验和伤口愈合试验证实，UMUC-3细胞中的MSCs的促肿瘤作用可以被抑制。为了在体内验证上述结果，研究人员进行了裸鼠异种移植实验。研究人员进一步探究了IDO1i是否通过调节线粒体的质量和数量来逆转MSCs的促肿瘤活性。为了确认IDO1i对癌细胞增殖和迁移的影响确实是通过抑制MSCs的Kyn产生而介导的，研究人员使用siRNA敲低MSCs中的IDO1表达，并通过蛋白质免疫印迹实验分析进行了确认。然后，研究人员将si-IDO1 MSCs与BC细胞共培养。与对照组相比，si-IDO1 MSCs的促肿瘤能力显著降低，其中si-IDO1#2显示出最明显的效果。然而，当加入Kyn后，癌细胞的增殖和迁移能力又恢复了。 为了验证IDO1i林罗司他在体内的整体安全性，研究人员采用HE染色观察心脏、肝脏、脾脏、肺、肾脏、肠道和睾丸组织的形态。染色结果显示，主要器官未出现明显的药物相关损伤。 研究小结 04 综上，TME中的MSC会产生色氨酸代谢产物Kyn，通过激活AMPK途径增强线粒体功能，从而促进BC进展。IDO1抑制剂可以有效地逆转MSC对BC的促肿瘤作用。 【参考资料】 https://www-nature-com.libproxy1.nus.edu.sg/articles/s41419-024-07068-9 【关于投稿】 转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！ 转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。 热门推荐活动 点击免费报名 🕓 上海｜11月15日-16日 ▶ 2024第一届中国类器官转化医学大会 点击对应文字 查看详情

BORDEAUX, France--( BUSINESS WIRE )--RebrAIn, a pioneering precision neuro-surgery platform company, has recently received its second FDA 510(k) clearance for its OptimMRI software, which now includes a new machine learning model to assist in targeting the infero-lateral part of the VIM for lesioning techniques such as MRgFUS and Radiosurgery. This new software version already features FDA-cleared machine learning models for the STN and VIM regions of interest to assist in targeting Deep Brain Stimulation (DBS). RebrAIn has secured its second FDA 510(k) clearance in the past year, expanding the software's capabilities to include the infero-lateral part of the VIM. RebrAIn’s software as a medical device (SaMD) is designed to revolutionize neurosurgical target planning by combining advanced AI algorithms, trained on clinical data, with MRI sequences to provide neurosurgeons with the most optimal targets for lesioning and electrode placement. David Caumartin, CEO of RebrAIn, stated, “Our extension to US customers to better plan targets for lesioning is a significant step in RebrAIn’s growth and strategic transformation. The US market represents the largest opportunity to enable personalized targeting for neurological disorders such as Essential Tremor. The ability to offer AI clinical targeting to neurosurgical suites will open many collaborations nationwide, which today are treated with DBS and MR-guided focused ultrasound. Since our recent discussions at US congresses, it was necessary for us to offer neurosurgeons a complete service.” RebrAIn’s co-founders, Prof. Emmanuel Cuny MD and Prof. Nejib Zemzemi PhD, will be presenting on “VIM Lesions in Radiosurgery and Focused Ultrasound: Assessment of the Accuracy of Two Targeting Models Based on Machine Learning” at the World Society for Stereotactic and Functional Neurosurgery (WSSFN) biennial meeting in Chicago, IL, on September 5, 2024. “Our extension to US customers to better plan targets for lesioning is a significant step in RebrAIn’s growth and strategic transformation,” said David Caumartin, CEO of RebrAIn. “The US market is the largest, and the ability to offer AI clinical targeting will open many national collaborations.” To learn more, visit us at Booth #9 during the WSSFN meeting, check out our website www.rebrain.eu , or contact us directly. About RebrAIn RebrAIn is a France-based company that enables precise targeting for DBS and lesioning treatments for patients suffering from severe Parkinson's or essential tremor disease. Its SaaS solution helps neurosurgeons to precisely identify the target area for surgical intervention. Its novel approach uses machine learning of clinical patient data to predict the optimal treatment zone in each patient’s brain. For more information, visit www.rebrain.eu . About the World Society for Stereotactic and Functional Neurosurgery Since 1961, the WSSFN has been regularly held and continues to be a leading neurosurgery conference. At the biennial meetings, the top leaders in the field present the most recent innovations in clinical and basic research as well as new and effective ways to provide material support. Meta Description: "RebrAIn receives its second FDA 510(k) clearance for OptimMRI software, enhancing targeting in stereotactic and functional neurosurgery for Deep Brain Stimulation and lesioning techniques. The company will present VIM targeting advancements at the WSSFN congress." Tags: FDA 510(k) Clearance, Deep Brain Stimulation (DBS), Stereotactic Neurosurgery, Functional Neurosurgery, Medical Device Software, Machine Learning in Healthcare, MR-guided Focused Ultrasound (MRgFUS), Radiosurgery, Neurotechnology, WSSFN Congress, RebrAIn, Essential Tremor Treatment, AI in Healthcare, Precision Neurosurgery, Healthcare Innovations.