English Journal

Determining ProGRP and isoforms in lung and thyroid cancer patient samples: comparing an MS method with a routine clinical immunoassay.

Torsetnes SB1, Broughton MN, Paus E, Halvorsen TG, Reubsaet L.Author information 1Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316, Oslo, Norway.AbstractThis paper compares two methods to determine the tumor marker progastrin-releasing peptide (ProGRP): as routine assay, the automated time-resolved immunofluorometric assay (TR-IFMA), which allows total ProGRP determination; and the immunocapture liquid chromatography selected reaction monitoring mass spectrometry (LC-SRM-MS) method, which additionally allows isoform differentiation. The investigation included 60 serum samples from patients suffering from various cancer diseases which may cause elevated ProGRP levels (small cell lung carcinoma; SCLC, non-small cell lung carcinoma; NCLC; and medullary thyroid cancer; MTC, as well as some with unspecific diagnosis). The two methods showed good correlation (R 2 = 0.887). However, the MS method determines the total ProGRP concentration systematically approximately 30 % lower than the TR-IFMA, implying that the absolute values generated by the methods are not interchangeable. The MS method gives additional information about isoform levels in the samples, providing novel insight into isoform expression on the protein level.
Analytical and bioanalytical chemistry.Anal Bioanal Chem.2014 Feb 12. [Epub ahead of print]
This paper compares two methods to determine the tumor marker progastrin-releasing peptide (ProGRP): as routine assay, the automated time-resolved immunofluorometric assay (TR-IFMA), which allows total ProGRP determination; and the immunocapture liquid chromatography selected reaction monitoring mas
PMID 24518900

The prognostic significance of the circulating neuroendocrine markers chromogranin A, pro-gastrin-releasing peptide, and neuron-specific enolase in patients with small-cell lung cancer.

Petrović M1, Bukumirić Z, Zdravković V, Mitrović S, Atkinson HD, Jurišić V.Author information 1Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.AbstractLung cancer is the most common cancer, and small-cell lung cancer (SCLC) accounts for around 20 % of lung cancers. SCLC has a neuroendocrine cellular origin, and the tumor cells usually express neuroendocrine markers. There have been major recent advances in the management of SCLC, and multimodal approaches are now the norm. An improved knowledge of the prognostic variables would assist in defining which patients were better candidates to receive these newer intensive therapies. This single-center retrospective study of 97 previously untreated and histologically proven SCLC patients analysed the circulating neuroendocrine markers chromogranin A (CGA), pro-gastrin-releasing peptide (ProGRP), and neuron-specific enolase (NSE) in addition to the other more classical variables. Fifty patients had limited-stage disease and 47 had extensive disease. Sixty patients had an ECOG performance status (PS) of 0-1 and 37 had PS 2-4. Median survival for the whole study population was 13 months. Univariate analysis and univariate Cox regression modeling found a statistically significant association between survival and PS, disease stage, and CGA, ProGRP, and NSE levels. Age and sex were not prognostic. A shorter survival time was found in patients with a PS equal to or >2, extensive stage disease, a serum CGA level >56 ng/ml, a serum ProGRP level >58 pg/ml, and a serum NSE level >19 ng/ml. This study has found that there is a potential role for ProGRP, NSE, and CGA in both staging and prognosing survival in SCLC patients.
Medical oncology (Northwood, London, England).Med Oncol.2014 Feb;31(2):823. doi: 10.1007/s12032-013-0823-1. Epub 2013 Dec 30.
Lung cancer is the most common cancer, and small-cell lung cancer (SCLC) accounts for around 20 % of lung cancers. SCLC has a neuroendocrine cellular origin, and the tumor cells usually express neuroendocrine markers. There have been major recent advances in the management of SCLC, and multimodal a
PMID 24375395

Integrated enzyme reactor and high resolving chromatography in "sub-chip" dimensions for sensitive protein mass spectrometry.

Hustoft HK1, Brandtzaeg OK1, Rogeberg M2, Misaghian D1, Torsetnes SB3, Greibrokk T1, Reubsaet L3, Wilson SR1, Lundanes E1.Author information 1Department of Chemistry, University of Oslo, Post Box 1033 Blindern, NO-0315 Oslo, Norway.21] Department of Chemistry, University of Oslo, Post Box 1033 Blindern, NO-0315 Oslo, Norway [2] Department of Neurology, Akershus University Hospital, 1478 Lørenskog, Norway.3School of Pharmacy, University of Oslo, Post Box 1068 Blindern, NO-0316 Oslo, Norway.AbstractReliable, sensitive and automatable analytical methodology is of great value in e.g. cancer diagnostics. In this context, an on-line system for enzymatic cleavage of proteins, subsequent peptide separation by liquid chromatography (LC) with mass spectrometric detection has been developed using "sub-chip" columns (10-20 μm inner diameter, ID). The system could detect attomole amounts of isolated cancer biomarker progastrin-releasing peptide (ProGRP), in a more automatable fashion compared to previous methods. The workflow combines protein digestion using an 20 μm ID immobilized trypsin reactor with a polymeric layer of 2-hydroxyethyl methacrylate-vinyl azlactone (HEMA-VDM), desalting on a polystyrene-divinylbenzene (PS-DVB) monolithic trap column, and subsequent separation of resulting peptides on a 10 μm ID (PS-DVB) porous layer open tubular (PLOT) column. The high resolution of the PLOT columns was maintained in the on-line system, resulting in narrow chromatographic peaks of 3-5 seconds. The trypsin reactors provided repeatable performance and were compatible with long-term storage.
Scientific reports.Sci Rep.2013 Dec 16;3:3511. doi: 10.1038/srep03511.
Reliable, sensitive and automatable analytical methodology is of great value in e.g. cancer diagnostics. In this context, an on-line system for enzymatic cleavage of proteins, subsequent peptide separation by liquid chromatography (LC) with mass spectrometric detection has been developed using "sub-
PMID 24336509

Japanese Journal

皮膚筋炎の発症を契機に診断された小細胞肺癌の1 例

戸田正夫,大西祥五,増田浩之,原澤寛,中元隆明,曾田紗世,神谷周良,福島康次,石井芳樹,福田健
Dokkyo journal of medical sciences 38(1), 127-134, 2011-03-25
… ALD, AST, LDH 等筋原性酵素の著明上昇及び臨床所見により皮膚筋炎と診断された.高用量ステロイド療法その後シクロスポリンの追加にて治療開始し,検査所見に続き,臨床所見も改善傾向にあった.同時にproGRP 高値並びに全身CT 画像上縦隔リンパ節腫大認め,気管支鏡下気管支粘膜生検にて小細胞肺癌の病理診断が得られ,CBDCA+CPT-11 にて化学療法を施行,腫瘍の縮小効果を見た.皮膚筋炎が腫瘍随伴症候として,小細胞癌 …
NAID 110008464231

尿管原発小細胞癌の1例

小泉孔二,中藤亮,井上善博 [他]
泌尿器科紀要 57(1), 21-24, 2011-01
… The serum ProGRP was slightly elevated postoperatively. …
NAID 120002770964

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★リンクテーブル★

国試過去問	「112B038」「111I015」
リンク元	「腫瘍マーカー」「ガストリン放出ペプチド前駆体」

「112B038」

　　[★]

50歳の男性。咳嗽を主訴に来院した。2か月前から咳嗽があり、他院で肺炎と診断され抗菌薬を処方されたが改善しないため受診した。喫煙は40本/日を30年間。意識は清明。身長 175cm、体重 78kg。体温 36.5℃。脈拍 88/分、整。血圧 126/80mmHg。呼吸数 15/分。SpO2 96%(room air)。心音と呼吸音とに異常を認めない。血液所見：赤血球 508万、Hb 14.8g/dL、白血球 5,600、血小板 25万。血液生化学所見：総ビリルビン 0.6mg/dL、AST 10U/L、ALT 21U/L、LD 425U/L(基準 176～353)、尿素窒素 14mg/dL、クレアチニン 1.2mg/dL、CEA 2.9ng/mL(基準 5.0以下)、SCC 1.2ng/mL(基準 1.5以下)、ProGRP 350pg/mL(基準 81以下)。CRP 0.3mg/dL。胸部エックス線写真(別冊No. 4Ａ)と胸部CT(別冊 No. 4Ｂ)とを別に示す。気管支鏡下生検で肺癌と診断された。
肺癌の組織型として最も可能性が高いのはどれか。

[正答]

※国試ナビ4※　［112B037］←［国試_112］→［112B039］

「111I015」

　　[★]

小細胞肺癌で高値を示すのはどれか。

a　CEA
b　SCC
c　AFP
d　ProGRP
e　PIVKA-Ⅱ

[正答]

※国試ナビ4※　［111I014］←［国試_111］→［111I016］

「腫瘍マーカー」

　　[★]

英: tumor marker
同: 生物学的腫瘍マーカー biological tumor marker、癌マーカー cancer marker、悪性腫瘍特異物質 tumor-specific antigen

肺癌の腫瘍マーカー

	陽性率(疾患があるときに陽性となる確率, 感度)
	肺癌					備考
	肺癌	扁平上皮癌	腺癌	小細胞癌	その他の疾患
CYFRA21-1	57.5%*	70-80%/73.1%*	30-40%	30-40%	良性疾患:10-15%
SCC		○			子宮頸癌、食道癌、皮膚癌
CEA	40-50%		50-60%
SLX	70%*		0.4		肝硬変
NSE	10-30%			70-90%
proGRP				70-90%/65.1%*		NSEより上昇率が高く、特異性に優れる
KL-6		○			肺腺癌、膵癌、乳癌で40-50%。間質性肺炎の補助診断

無印：標準呼吸器病学第1版 p.327。* 臨床検査学第32版 p.634

臨床応用されている腫瘍マーカー (LAB.630)

肝癌関連　AFP, AFP-L3%, PIVKA-II
膵癌ならびにその他の消化器癌　CEA, CA19-9, Dupan-2, CA50, Span-1
肺癌　CEA, sialyl Lex-i (SLX), SCC, SYFRA21-1, NSE, ProGRP
婦人科悪性腫痩
　子宮癌：SCC, CA125
　卵巣癌：CA125, AFP, CEA, CA19-9, GAT
　乳癌　：CA15-3, BCA225, CEA, NCC-ST-439
尿器科悪性腫壕
　前立腺痛：PSA(γ-Sm), PAP
　膀胱癌　：BTA, NMP22
　神経内分泌腫療　NSE
　広範な腫瘍に反応するマーカー
　　TPA, BFP, IAP

消化管悪性腫瘍マーカー

CEA：胎児癌性蛋白。陽性率：(50-70%)大腸癌、胆道癌、膵癌。(40-60%)肺癌。(30-40%)胃癌。良性疾患でも上昇する(胆嚢炎、胆管炎、膵炎)。
DU-PAN-2：2→3シアリルLec抗原を認識する抗体。陽性率：(70-80%)膵癌、(60-70%)胆道癌。Lea-b-の個体でも陽性になる。良性疾患でも上昇する(慢性肝炎、肝硬変、胆道炎症を伴う胆石症)。
CA19-9：Leaの基本骨格にシアル酸が結合したもの。陽性率：(80-90%)膵癌。(70-80%)胆道癌。良性疾患でも上昇する((10-40%)閉塞性黄疸、慢性肝炎、肝硬変)。日本人の約7-10%に存在するフコース転移酵素が欠如したLea-b-の個体ではCA19-9は産生されない。
SLX：Lexの基本骨格にシアル酸が結合したもの。陽性率：(高い)肺癌、卵巣癌。(50-60%)胆道癌、膵癌。

主な腫瘍マーカー CBT QB vol2 p.297

AFP	肝細胞癌、肝芽腫、卵黄脳腫瘍
CEA	消化器系の癌、肺癌、乳癌(腺癌の頻度が高く、臓器特異性は低い)
CA19-9	胆道系の癌、膵癌
CA125	卵巣癌
CA15-3	乳癌、卵巣癌
PIVKA-II	肝細胞癌
PSA	前立腺癌

組織型別に有用な腫瘍マーカー(NEWエッセンシャル産科学・婦人科学第3版 p.236)

上皮性腫瘍
　漿液性腺癌: CA125 *1
　粘液性腺癌: CA19-9 *2, CA72-4, CEA
胚細胞腫瘍
　卵黄嚢腫瘍: AFP *3
　絨毛癌: hCG
　未分化胚細胞腫: LDH *4
　悪性転化を伴う成熟嚢胞性奇形腫(扁平上皮癌) : SCC
性索間質性腫瘍(ホルモン)
　顆粒膜細胞腫,莢膜細胞腫:工ストロゲン
　Sertoli-間質性腫瘍, Leydig細胞腫(門細胞腫) :テストステロン
*1　上皮性腫瘍中で最も有用.類内膜腺癌,明細胞腺癌でも陽性を示す.子宮内膜症,炎症,妊娠初期も軽度-中等度上昇
*2　成熟嚢胞性奇形腫で陽性を示すことがある
*3　胎芽性癌,混合性腔細胞腫療でも陽性を示す
*4　非特異的