Goossens et al., Cancer biomarker discovery and validation.Transl Cancer Res. 2015 Jun; 4(3): 256–269. there has been a large gap between multiple initial reports of biomarkers, often with diagnostic performance that cannot be reproduced in later studies
Henry and Hayes. Cancer biomarkers Molecular Oncology06 February 2012
Strategies for discovering novel cancer biomarkers through utilization of emerging technologies. Clinical Practice http://sites.utoronto.ca/acdclab/pubs/PM/18695711.pdf The introduction of technologies such as mass spectrometry and protein and DNA arrays, combined with our understanding of the human genome, has enabled simultaneous examination of thousands of proteins and genes in single experiments, which has led to renewed interest in discovering novel biomarkers for cancer.中略 Cancer biomarkers can be DNA, mRNA, proteins, metabolites, or processes such as apoptosis, angiogenesis or proliferation.
がんマーカーとしての変異遺伝子
発がんは多くの場合、遺伝子の変異の蓄積を伴います。
K-Ras変異とがん
epidermal growth factor receptorの変異とがん
c-Kitの変異とがん
Braf の変異とがん
Andre et al., Biomarker Discovery, Development, and Implementation in France: A Report from the French National Cancer Institute and Cooperative Groups. March 2012 Clinical Cancer Research March 2012 Volume 18, Issue 6
がんマーカーとしての細胞外小胞の利用
Kosaka et al., Exploiting the message from cancer: the diagnostic value of extracellular vesicles for clinical applications.Experimental & Molecular Medicine 15 March 2019; volume 51, pages1–9. https://www.nature.com/articles/s12276-019-0219-1 細胞外小胞の種類を説明した図がわかりやすい
乳がん
Comment on ‘BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses’ 15 March 2018 British Journal of Cancervolume 118, pages 1152–1153
Circulating Microparticles in Breast Cancer Patients: A Comparative Analysis with Established Biomarkers. ANTICANCER RESEARCH 28: 1107-1112 (2008)
TNBC
Sukumar et al., Triple-negative breast cancer: promising prognostic biomarkers currently in development.Expert Review of Anticancer Therapy24 Feb 2021
Biomarkers in Triple-Negative Breast Cancer: State-of-the-Art and Future Perspectives.Int J Mol Sci. 2020 Jul; 21(13): 4579. MDPIジャーナルに掲載されたレビュー論文 Lehmann et al. proposed a division of TNBCs into seven molecular subtypes: immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), luminal androgen receptor (LAR), unstable (UNS) subtype, and two basal-like subtypes (BL1 and BL2) [3]. Then, a subclassification refinement was performed, to define only four groups BL1 (immune-activated), BL2 (immune-suppressed), M (including most of the MSL), and LAR [4]. These classifications can, in theory, be used as prognostic and predictive tool for better patient selection and personalized treatments. 中略 However, sound clinical applications of this molecular classification are yet to appear [8]. 個別化医療のためのTNBC
のタイプ分けの努力とその限界
Bao et al. Exploring specific prognostic biomarkers in triple-negative breast cancer. Fan Cell Death & Disease 24 October 2019; volume 10, Article number: 807
Potential clinically useful prognostic biomarkers in triple-negative breast cancer: preliminary results of a retrospective analysis.Breast Cancer (Dove Med Press). 2018 Nov 23; 10: 177–194.
Lafont et al., CD73: a new biomarker in triple-negative breast cancer.Translational Cancer ResearchVol 7, Supplement 5 (June 2018)
大腸がんのマーカー蛋白質
Zheng et al., A circulating extracellular vesicles-based novel screening tool for colorectal cancer revealed by shotgun and data-independent acquisition mass spectrometry. Journal of Extracellular Vesicles 14 April 2020; Volume 9, Issue 1
Zhong et al. Serum extracellular vesicles contain SPARC and LRG1 as biomarkers of colon cancer and differ by tumour primary location. EBioMedicine 2019 Nov 18; 50:211-223.
Lee et al. Discovery of a diagnostic biomarker for colon cancer through proteomic profiling of small extracellular vesicles. BMC Cancer. 2018 Nov 1; 18: 1058.
Quantitative mass spectrometry analysis reveals a panel of nine proteins as diagnostic markers for colon adenocarcinomas. Oncotarget. 2018 Mar 2; 9(17): 13530–13544.
Shiromizu et al., Quantitation of putative colorectal cancer biomarker candidates in serum extracellular vesicles by targeted proteomics.Scientific Reports 06 October 2017 ; volume 7, Article number: 12782. annexins A3, A4, and A11
The Lymphocyte-to-Monocyte Ratio is a Superior Predictor of Overall Survival in Comparison to Established Biomarkers of Resectable Colorectal Cancer. Ann Surg. 2017 Mar; 265(3): 539–546.
Area Under the Curve One of the most important pharmacokinetic parameters is the area under the drug concentration versus time curve within the dosing interval (AUC) because AUC relates dose to exposure. Because the dosing interval is typically once daily or every 24 h on safety studies, the reported AUC is typically AUC0–24 h. AUC is the quantitative measure of the apparent amount of compound at the site from which samples were collected and concentrations measured, which in most cases is the systemic circulation. When sampling occurs from the systemic circulation, it is often an indication of systemic exposure. The simplest method for calculating AUC is the linear trapezoidal rule (Gibaldi and Perrier 1982). (sciencedirect.com)
The Origin and Understanding of the Incretin Concept.Front Endocrinol(Lausanne). 2018; 9: 387. Published online 2018 Jul 16. doi: 10.3389/fendo.2018.00387 PMCID: PMC6054964 PMID: 30061863 In gastrointestinal endocrinology, the concept of incretin is today highly topical and generally applied to two distinct gut hormones with technical acronymous names: GIP (originally “gastric inhibitory polypeptide,” later renamed “glucose-dependent insulinotropic polypeptide”) and GLP-1 [“glucagon-like peptide 1,” now in its truncated (7–36) form]. ‥ it was the Belgian physiologist Jean La Barre who coined the word “incrétine” in 1932.
La Barre J. Sur les possibilités d’un traitement du diabète par l’incrétine. Bull Acad Royal Med Belg. (1932) 12:620–34.
この概念に当てはまる物質として、GIPやGLP-1が同定されました。
The two main candidate molecules that fulfill criteria for an incretin are the intestinal peptides glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP, also known as: glucose-dependent insulinotropic polypeptide). (incretin Wikipedia)
インクレチン（incretin）は、「膵臓のランゲルハンス島β細胞を刺激して、血糖値依存的にインスリン分泌を促進する消化管ホルモン」として定義され、具体的にはグルコース依存性インスリン分泌刺激ポリペプチド（glucose-dependent insulinotropic polypeptide：GIP）とグルカゴン様ペプチド-1 （glucagon-like peptide-1：GLP-1）の２つを指す。GIP は上部消化管に存在する腸内分泌細胞 （enteroendocrine cells）の一種である K 細胞が含有し、GLP-1 は下部消化管の腸内分泌細胞である L 細胞が含有する。（用語集 腸内細菌学会）
発熱や感染症で抗菌薬を処方される事がありますが、長期にわたり飲み続けると消化管に住んでいる「賢い菌」の住む環境が悪くなり、代わりに毒素を出す「悪い菌」（クロストリジウムディフィシレ）が増え、腸炎や下痢を起こし、その下痢便から排出された病原菌が病院などで拡がる事が問題になっております。（注目の抗菌薬関連下痢症（クロストリジウムディフィシル）について Infection control nurseの部屋）
Multiplex PCR for Detection and Identification of Microbial Pathogens Mark A. PoritzEmail authorBeth Lingenfelter 1. 2. Chapter First Online: 10 November 2018 Advanced Techniques in Diagnostic Microbiology pp 475-493|
Multicenter evaluation of Verigene Enteric Pathogens Nucleic Acid Test for detection of gastrointestinal pathogens. 04 February 2021
Impact of Verigene Multiplex PCR for Positive Blood Cultures and Gram-negative Bacteremia. Open Forum Infect Dis. 2017 Fall; 4(Suppl 1): S625. Published online 2017 Oct 4. doi: 10.1093/ofid/ofx163.1654 PMCID: PMC5630765
Commercially available FDA-cleared multiplex nucleic acid-based tests for infectious agents include systems from Luminex, GenMark, and BioFire (now a subsidiary of bioMérieux) (Table 1). At present, all such systems combine the sequential steps of:
Nucleic acid purification from the appropriate human sample matrix (e.g., nasal swab, blood or blood culture, stool)
cDNA synthesis (reverse transcription) to convert viral RNA to DNA, if necessary
Multiplex PCR to amplify molecules of the pathogen nucleic acid
Specific detection of the expected amplicons to confirm that the correct target nucleic acids have been identified
（Multiplex PCR for Detection and Identification of Microbial Pathogens 10 November 2018 Advanced Techniques in Diagnostic Microbiology pp 475-493）
Multiplex PCR system for the rapid diagnosis of respiratory virus infection: systematic review and meta-analysis. Clinical Microbiology and Infection Volume 24, Issue 10, October 2018, Pages 1055-1063 diagnostic accuracies of three multiplex PCR systems (mPCRs)—BioFire FilmArray RP (FilmArray), Nanosphere Verigene RV+ test (Verigene RV+) and Hologic Gen-Probe Prodesse assays—on the detection of viral respiratory infections.
Multiplex PCR for Detection and Identification of Microbial Pathogens 10 November 2018 Advanced Techniques in Diagnostic Microbiology pp 475-493
The FILMARRAY is an FDA-cleared multiplex PCR system that integrates sample preparation, amplification, detection and analysis. It requires just a few minutes of hands-on-time and its turnaround time is just about an hour, giving you faster results which may lead to better patient care. (biomerieux-usa.com)
BioFire® FilmArray® System Demo 2013/04/06 BioFire Diagnostics
診療科に合わせて検出したい病原体のパネルが用意されているようです。
バイオファイアのフィルムアレイ特許
SALT LAKE CITY, Utah,(March13, 2013) –BioFire Diagnostics,Inc.,today announced that the United States Patent and Trademark Office has issued U.S.Patent No. 8,394,608 covering the company’s FilmArray system. FilmArray’s proprietary technology represents a significant advancement in user-friendliness and multiplex infectious disease testing capability for hospital clinical labs. This is the first U.S. patent issued to cover the FilmArray system, and BioFire has exclusive rights to the patented technology. Specifically, the patent covers methods for sample preparation and two-step multiplex polymerase chain reaction (PCR) in a sealed container. (BioFire Diagnostics)
The FilmArray Blood Culture Identification (BCID) panel, which is able to identify 24 different microorganisms and the resistance genes Klebsiella pneumoniae carbapenemase (KPC), mecA and vanA/B, has the potential to facilitate point-of-care testing and provides results in 1 hour. (Application of BioFire FilmArray Blood Culture Identification panel for rapid identification of the causative agents of ventilator-associated pneumonia. Clinical Microbiology and Infection Volume 24, Issue 11, November 2018, Pages 1213.e1-1213.e4)
BioFire FilmArray Meningitis/Encephalitis panel
The BioFire FA ME addresses such diagnostic underutilization by providing a comprehensive panel testing for 15 CNS pathogens simultaneously using a minimal amount of CSF with rapid turn-around time (1 h). Shown to be an effective alternative for other infections such as gastroenteritis [3], and bacteremia [5–8] BioFire’s FA ME was approved by the Federal Drug Administration on October 8, 2015 with promising results both in the US [9] and internationally [10, 11]. (Enhancing pathogen identification in patients with meningitis and a negative Gram stain using the BioFire FilmArray® Meningitis/Encephalitis panel. Annals of Clinical Microbiology and Antimicrobials volume 15, Article number: 26 (2016))
BioFire FilmArray Pneumonia Panel
The BioFire FilmArray pneumonia panel (BFPP) was recently FDA cleared (November 2018) for detection and identification of multiple respiratory viral and bacterial pathogens in addition to selected antimicrobial resistance genes from sputum or bronchial alveolar lavage (BAL)-like specimens from individuals with suspected lower respiratory tract (LRT) infections. This assay includes targets for 18 bacteria and 8 viruses that commonly cause pneumonia as well as 7 antibiotic resistance genes. (Evaluation of the BioFire FilmArray Pneumonia Panel for Detection of Viral and Bacterial Pathogens in Lower Respiratory Tract Specimens in the Setting of a Tertiary Care Academic Medical Center. Journal of Clinical Microbiology)
The BioFire FilmArray Pneumonia Panel (FA-Pneumo; BioFire Diagnostics, Salt Lake City, UT, USA) was recently cleared by the US Food and Drug Administration (US FDA, Washington, DC, USA). FA-Pneumo is a fully automated multiplex PCR assay for identifying a number of typical and atypical bacterial pathogens, respiratory viruses, and several classes of antimicrobial susceptibility-associated genes directly from sputum, endotracheal aspirate (ETA), and bronchoalveolar lavage-like specimens in approximately 1 h (Table 1). The assay provides semi-quantitative results for 15 typical respiratory bacterial pathogens.
Table 1. FilmArray Pneumonia Panel plus targets.
Typical bacteria
Acinetobacter calcoaceticus–baumannii complex
Enterobacter cloacae complex
Escherichia coli
Haemophilus influenzae
Klebsiella aerogenes
Klebsiella oxytoca
Klebsiella pneumoniae group
Moraxella catarrhalis
Proteus spp
Pseudomonas aeruginosa
Serratia marcescens
Staphylococcus aureus
Streptococcus agalactiae
Streptococcus pneumoniae
Streptococcus pyogenes
Atypical bacteria
Chlamydia pneumoniae
Legionella pneumophila
Mycoplasma pneumoniae
Viruses
Adenovirus
Human metapneumovirus
Human rhinovirus/enterovirus
Influenza A
Influenza B
Parainfluenza virus
Respiratory syncytial virus
Antimicrobial resistance genes
Methicillin resistance
mecA/C and MREJ
Extended-spectrum β-lactamase
CTX-M
Carbapenemases
NDM, IMP, OXA-48-like, KPC, and VIM
(Evaluation of the BioFire FilmArray Pneumonia Panel for rapid detection of respiratory bacterial pathogens and antibiotic resistance genes in sputum and endotracheal aspirate specimens. International Journal of Infectious Diseases Volume 95, June 2020, Pages 326-331)
The BioFire® FilmArray® Gastrointestinal (GI) Panel The FDA-cleared BioFire GI Panel tests for 22 of the most common pathogens associated with gastroenteritis—all from one patient sample and one easy to use reagent, with results available in about one hour.
Impact of the BioFire FilmArray gastrointestinal panel on patient care and infection control. February 6, 2020 PLOS ONE Routine PCR detected one or more pathogens in 52 (28.6%) patients compared to 72 (39.6%) using the FilmArray. Turnaround time (including transport) decreased from median 53 hours for the routine PCR to 16 hours for the FilmArray.
Evaluation of the BioFire FilmArray Gastrointestinal Panel and Real-Time Polymerase Chain Reaction Assays for the Detection of Major Diarrheagenic Pathogens by a Multicenter Diarrheal Disease Surveillance Program in China Foodborne Pathogens and Disease Vol. 16, No. 11
Contribution of the FilmArray® Gastrointestinal Panel in the laboratory diagnosis of gastroenteritis in a cohort of children: a two-year prospective study International Journal of Medical Microbiology Volume 308, Issue 5, July 2018, Pages 514-521
FilmArray™ GI panel performance for the diagnosis of acute gastroenteritis or hemorragic diarrhea 12 May 2017 BMC Microbiology volume 17, Article number: 111 (2017)
Multicenter Evaluation of the BioFire FilmArray Gastrointestinal Panel for Etiologic Diagnosis of Infectious Gastroenteritis. 19 February 2015Journal of Clinical Microbiology Vol. 53, No. 3
