Breast Cancer: Early diagnosis using materials immortalisation

乳腺癌：利用材料永生化进行早期诊断

• 批准号: MR/T000406/1
• 负责人: K Rogers
• 金额: $ 121.53万
• 依托单位: CRANFIELD UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT000406%2F1
• 关键词: Breast; Cancer; Early; diagnosis; using

Within the UK there are >55000 new cases of breast cancer diagnosed every year (world-wide >1.7 million) and the economic cost of breast cancer to the UK is >£1.5bn per annum. Early and accurate diagnoses are critical for the most effective treatments and reduced costs. Current diagnostic inadequacies are characterised by (i) an >80% false positive rate for mammography, (ii) significant overtreatment of some breast cancers, and, (iii) equivocal histopathology leading to uncertain prognoses.This proposal will generate a new understanding of the physicochemistry of involved tissues and, as a result, will identify potential new biomarkers and diagnostic methods. We will adopt a new, multidisciplinary approach to disease diagnosis, and combine the expertise of senior clinicians with material scientists to study tissue physicochemistry. We will also exploit a distinct, retrospective approach to sampling that will enable access to unprecedented patient numbers. Successful outcomes from this work will have significant impacts for understanding disease and development of accurate breast cancer diagnostics.Calcifications within breast tissues are used as a primary marker of malignancy although the precipitation mechanism of biologically derived calcifications remains a matter of considerable debate. In contrast, the capacity of apatites to incorporate 'foreign', environmental ions at the time of precipitation is incontrovertible. Thus chemical features of tissue physiology at the point of formation become immortalised within calcifications. Precipitation of calcific phases in vivo is triggered by slight modifications to tissue chemistry and this, in the case of breast tissue, occurs at the very onset of the cancer.Our primary hypothesis then is that apatite calcification physicochemical characteristics may be employed as novel biomarkers of cancer. The primary aim of this project is to determine and understand the underpinning physicochemical characteristics of breast tissue calcifications to enable future development of in vivo, accurate diagnostic probes. The project will (a) identify archived specimen populations representing a wide range of tumour subtypes for material analyses, (b) exploit cutting edge physical methods of high resolution calcification characterisation and, (c) relate calcification physicochemistry to clinical diagnosis and prognosis.Successful outcomes from this work will have significant impacts for understanding disease and development of accurate breast cancer diagnostics.

在英国，每年诊断出的乳腺癌新病例超过 55000 例（全世界超过 170 万例），乳腺癌给英国造成的经济损失每年超过 15 亿英镑。早期准确的诊断对于最有效的治疗和降低成本至关重要。目前诊断不足的特点是（i）乳房X光检查的假阳性率>80%，（ii）某些乳腺癌的严重过度治疗，以及（iii）组织病理学模棱两可导致预后不确定。该提案将对相关组织的物理化学产生新的理解，从而确定潜在的新生物标志物和诊断方法。我们将采用一种新的、多学科的方法来进行疾病诊断，并结合高级临床医生和材料科学家的专业知识来研究组织物理化学。我们还将采用一种独特的回顾性抽样方法，以获取前所未有的患者数量。这项工作的成功结果将对了解疾病和开发准确的乳腺癌诊断产生重大影响。尽管生物来源的钙化的沉淀机制仍然存在相当大的争议，但乳腺组织内的钙化被用作恶性肿瘤的主要标志。相比之下，磷灰石在沉淀时吸收“外来”环境离子的能力是无可争议的。因此，组织生理学在形成时的化学特征在钙化中永久化。体内钙化相的沉淀是由组织化学的轻微改变引发的，对于乳腺组织来说，这种沉淀发生在癌症一开始的时候。我们的主要假设是磷灰石钙化的物理化学特征可以用作癌症的新型生物标志物。该项目的主要目的是确定和了解乳腺组织钙化的基础物理化学特征，以便将来开发体内准确的诊断探针。该项目将（a）识别代表各种肿瘤亚型的存档样本群体进行材料分析，（b）利用高分辨率钙化表征的尖端物理方法，以及（c）将钙化物理化学与临床诊断和预后联系起来。这项工作的成功成果将对了解疾病和开发准确的乳腺癌诊断产生重大影响。

项目成果

A time-course Raman spectroscopic analysis of spontaneous in vitro microcalcifications in a breast cancer cell line.

• DOI: 10.1038/s41374-021-00619-0
• 发表时间: 2021-09
• 期刊: Laboratory investigation; a journal of technical methods and pathology
• 作者: Bouzy P;O'Grady S;Madupalli H;Tecklenburg M;Rogers K;Palombo F;Morgan MP;Stone N
• 通讯作者: Stone N

Abstract 5561: Molecular imaging of calcification and soft tissue defines prognosis of DCIS to invasive breast cancer

摘要 5561：钙化和软组织的分子成像确定 DCIS 与浸润性乳腺癌的预后

• DOI: 10.1158/1538-7445.am2023-5561
• 发表时间: 2023
• 期刊: Cancer Research
• 影响因子: 11.2
• 作者: Nallala J

Microcalcification crystallography as a potential marker of DCIS recurrence.

• DOI: 10.1038/s41598-023-33547-8
• 发表时间: 2023-06-08
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Gosling, Sarah;Arnold, Emily;Davies, Samantha;Cross, Hannah D.;Bouybayoune, Ihssane;Calabrese, Doriana D.;Nallala, Jayakrupakar;Pinder, Sarah;Fu, Liping;Lips, Esther J.;King, Lorraine;Marks, Jeffrey;Hall, Allison;Grimm, Lars;Lynch, Thomas;Pinto, Donna;Stobart, Hilary;Hwang, E. Shelley;Wesseling, Jelle;Geraki, Kalotina;Stone, Nicholas;Lyburn, Iain;Greenwood, Charlene;Rogers, Keith
• 通讯作者: Rogers, Keith

Exploration of utility of combined optical photothermal infrared and Raman imaging for investigating the chemical composition of microcalcifications in breast cancer.

• DOI: 10.1039/d2ay01197b
• 发表时间: 2023-03-30
• 期刊: ANALYTICAL METHODS
• 影响因子: 3.1
• 作者: Bouzy, Pascaline;Lyburn, Iain D.;Pinder, Sarah E.;Scott, Robert;Mansfield, Jessica;Moger, Julian;Greenwood, Charlene;Bouybayoune, Ihssane;Cornford, Eleanor;Rogers, Keith;Stone, Nick
• 通讯作者: Stone, Nick

A multi-modal exploration of heterogeneous physico-chemical properties of DCIS breast microcalcifications.

• DOI: 10.1039/d1an01548f
• 发表时间: 2022-04-11
• 期刊: The Analyst
• 作者: Gosling S;Calabrese D;Nallala J;Greenwood C;Pinder S;King L;Marks J;Pinto D;Lynch T;Lyburn ID;Hwang ES;Grand Challenge Precision Consortium;Rogers K;Stone N
• 通讯作者: Stone N