Microbial Surrogate Assay for Environmental PAH Exposure

环境 PAH 暴露的微生物替代测定

• 批准号: 8715044
• 负责人: Guy Richard Adami
• 金额: $ 14.85万
• 依托单位: ARPHION, LTD
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8715044
• 关键词: Behavior Therapy; Biological Assay; Carcinogen exposure; Carcinogens; Cells; Cessation of life; DNA; DNA Adduction; DNA Adducts; DNA Sequence; DNA analysis; Dental; Dentists; Diagnosis; Diagnostic; Disease; Enzymes; Ethanol; Exposure to; Fees; Food; Goals; Head and Neck Cancer; Head and neck structure; Health; Human; Knowledge; Link; Malignant Neoplasms; Mass Spectrum Analysis; Measurement; Measures; Mediating; Metabolism; Methods; Microbe; Minority; Mutagens; Neck Cancer; Oral; Oral cavity; Oral mucous membrane structure; Patients; Periodontal Diseases; Phase; Play; Population; Reporting; Research; Risk; Risk Assessment; Risk Factors; Role; Sampling; Services; Small Business Technology Transfer Research; Smoker; Staging; Swab; Testing; Tobacco; Tobacco smoke; Tobacco use; United States; Work; aryl hydrocarbons; base; cancer prevention; cancer risk; clinical research site; commercial application; experience; head and neck cancer patient; head and neck cancer prevention; high risk; improved; innovation; malignant mouth neoplasm; microbial; oral bacteria; oral microbiome; prevent; tool

DESCRIPTION (provided by applicant): Arphion is a company established to develop noninvasive products that will be used to diagnose, prevent, and treat head and neck and other cancers. 41,000 people are diagnosed with head and neck cancer (HNC) every year in the United States, with 8,000 deaths. Tens of millions of people in the US are at increased risk for HNC due to exposure to the polycyclic aryl hydrocarbons (PAHs) found in tobacco and some foods. Other risk factors are involved, because although many millions of people in the US are exposed to high levels of tobacco PAHs and a second risk factor, ethanol, only a small minority will get the disease. Curiously, the changes in oral bacteria that occur with tobacco-induced periodontal disease somehow also increase the risk for HNC. Dr. Joel Schwartz's team has recent evidence that may explain the connection between oral bacteria and cancer. They showed that tobacco users have excess numbers of 8 different oral microbial species that can metabolize PAHs, and that the metabolism can increase reactivity of these molecules. We hypothesis that these microbes, which we refer to as 8BAC, play a major role in DNA adduct formation in the oral mucosa, a key early step in formation of most HNC. Arphion plans to show that 8BAC is linked to mucosal DNA adduct formation in humans and that rapid PCR/DNA sequencing based measurement of 8BAC microbes in a patient's mouth will correlate to DNA adduct levels. Arphion's product would detect elevated levels of 8BAC as a surrogate for DNA adducts in cellular DNA, which are difficult and expensive to measure. Patients at high risk for HNC with high levels of 8BAC would be advised to change their tobacco consumption, and to have semiannual head and neck cancer exams. A second goal of this Phase I research is to show a firm link between 8BAC microbes and HNC by showing 8BAC is elevated in patients with this disease versus matched subjects who are HNC- free. Arphion's product will identify among smokers, and others with high carcinogen exposure, those most likely to go on to HNC. This will provide true cancer prevention by facilitating behavior modification. Our plan, after a successful Phase II, where we verify the link between 8BAC levels and mucosal DNA adduct levels, is to partner with a large firm with experience with automated DNA isolation and analysis, and knowledge of FDA regulatory requirements so we can begin providing kits to dental practitioners who will then send preserved samples to Arphion for analysis on a fee-for-test basis.

描述（由申请人提供）：Arphion 是一家为开发用于诊断、预防和治疗头颈癌及其他癌症的非侵入性产品而成立的公司。美国每年有 41,000 人被诊断患有头颈癌 (HNC)，其中 8,000 人死亡。由于接触烟草和某些食品中的多环芳烃 (PAH)，美国有数以千万计的人患 HNC 的风险增加。还涉及其他风险因素，因为尽管美国有数百万人接触高浓度的烟草多环芳烃和第二个风险因素乙醇，但只有一小部分人会患上这种疾病。奇怪的是，烟草引起的牙周病引起的口腔细菌变化在某种程度上也增加了患 HNC 的风险。乔尔·施瓦茨博士的团队最近有证据可以解释口腔细菌与癌症之间的联系。他们表明，烟草使用者体内有过量的 8 种不同的口腔微生物物种可以代谢多环芳烃，并且代谢可以增加这些分子的反应性。我们假设这些微生物（我们称之为 8BAC）在口腔粘膜 DNA 加合物的形成中发挥着重要作用，这是大多数 HNC 形成的关键早期步骤。 Arphion 计划证明 8BAC 与人类粘膜 DNA 加合物的形成有关，并且基于快速 PCR/DNA 测序的患者口腔中 8BAC 微生物的测量将与 DNA 加合物水平相关。 Arphion 的产品将检测升高水平的 8BAC，作为细胞 DNA 中 DNA 加合物的替代物，而这种方法的测量既困难又昂贵。建议 8BAC 水平较高的 HNC 高风险患者改变烟草消费，并每半年进行一次头颈癌检查。这项 I 期研究的第二个目标是通过显示患有这种疾病的患者与无 HNC 的匹配受试者相比 8BAC 升高，来证明 8BAC 微生物与 HNC 之间的牢固联系。 Arphion 的产品将在吸烟者和其他高致癌物暴露人群中进行识别，这些人最有可能继续接受 HNC。这将通过促进行为改变来提供真正的癌症预防。在第二阶段成功验证 8BAC 水平和粘膜 DNA 加合物水平之间的联系后，我们的计划是与一家拥有自动化 DNA 分离和分析经验并了解 FDA 监管要求的大公司合作，以便我们可以开始向牙科医生提供试剂盒，然后牙科医生将保存的样本发送到 Arphion 进行收费分析。

项目成果

Enrichment of polycyclic aromatic hydrocarbon metabolizing microorganisms on the oral mucosa of tobacco users.

• DOI: 10.7717/peerj.16626
• 发表时间: 2024
• 期刊: PeerJ
• 影响因子: 2.7
• 作者: Tao L;Chiarelli MP;Pavlova S;Kolokythas A;Schwartz J;DeFrancesco J;Salameh B;Green SJ;Adami G
• 通讯作者: Adami G