血清ICTP,PICP,PIINP的检测对原发性肝癌骨转移的诊断意义

为了研究生血清ＩＣＴＰ，ＰＩＣＰ和ＰＩＩＮＰ的水平与原发性肝癌社骨转移的关系，采用放射免疫法检测了５０例原发性肝癌（骨转移３０例，无骨转移２０例）及２０例健康者血清中ＩＣＴＰ，ＰＩＣＰ和ＰＩＩＮＰ的水平。结果发现，原发性肝癌患者血清ＩＣＴＰ，ＰＩＩＮＰ显著高于健康者（Ｐ〈０．０１和Ｐ〈０．０５），其中伴骨转移的原发性肝癌血清ＩＣＴＰ，ＰＩＩＮＰ显著高于无骨转移者（Ｐ〈０．０１），但ＰＩＣＰ则无显著     

肺癌患者血清ＮＴｘ、ＩＣＴＰ和ＢＡＰ水平与骨转移的相关性研究

目的　探讨联合检测骨代谢生化指标血清Ⅰ型胶原氨基末端肽（ＮＴｘ）、Ⅰ型胶原羧基端肽（ＩＣＴＰ）及骨特异性碱性磷酸酶（ＢＡＰ）对诊断肺癌骨转移的临床意义。方法　选择经细胞学和病理学确诊的肺癌患者１０６例,分为两组,其中骨转移组６１例,无骨转移组４５例。用ＥＬＩＳＡ法检测两组患者血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ浓度。结果　骨转移组患者血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平分别为（２５.３６±１１.０７）ｎｍｏｌ／Ｌ、（２９.１８±１０.７４）μｇ／Ｌ和（７８.３１±１６.５３）μｇ／Ｌ,明显高于无骨转移组的（１２.１６±７.６２）ｎｍｏｌ／Ｌ、（１１.０２±５.３２）μｇ／Ｌ和（２４.０１±７.９８）μｇ／Ｌ,差异具有统计学意义（Ｐ＜０.０１）;ＮＴｘ、ＢＡＰ、ＩＣＴＰ诊断骨转移的灵敏度和特异度分别为９０.１６％和８４.４４％、８０.３２％和７７.７８％、７０.４９％和９１.１１％;多发骨转移组患者血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平明显高于单发骨转移组（Ｐ＜０.０５）;骨转移组患者血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平与疼痛程度呈正相关;不同性别、病理类型、转移部位患者的血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平差异无显著性（Ｐ＞０.０５）。结论　血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平对肺癌骨转移诊断的灵敏度和特异度较高,与骨转移数目和疼痛程度相关,是诊断肺癌骨转移的重要参考指标。     

uNTX、sICTP及sBALP表达在恶性肿瘤骨转移中的临床意义

目的探讨尿Ⅰ型胶原交联氨基末端肽（uNTX）、血清Ⅰ型胶原羧基末端肽（sICTP）及骨碱性磷酸酶（sBALP）表达在恶性肿瘤骨转移患者中的临床意义。方法对32例恶性肿瘤骨转移患者,在治疗前后分别采用酶联免疫吸附法（ELISA）、小麦菌凝集素沉淀法,测定uNTX、sICTP及sBALP水平。随访骨相关事件（SREs）及生存状况。结果患者基线uNTX/Cr、sICTP及sBALP水平明显高于正常,其浓度与骨转移负荷呈正相关性,与疼痛强度无显著相关性。治疗3个月时uNTX/Cr、sICTP及sBALP水平明显降低,而放射性核素全身骨显像（ECT）尚无明显改变;32例患者中24例基线uNTX/Cr水平高于正常水平,治疗后降至正常水平的15例患者骨相关事件发生率为53%,而治疗后仍维持在较高水平的9例患者为89%（P=0.039）;32例患者中27例基线sICTP水平高于正常,治疗后16例降至正常,11例仍维持在较高水平,两者骨相关事件发生率为50%和91%（P=0.032）;26例基线sBALP水平高于正常值,治疗后16例降至正常水平,10例仍维持在较高水平,两者骨相关事件发生率为50%和90%（P=0.038）。uNTX/Cr、sICTP及sBALP水平与肿瘤患者生存率无明显相关性。结论骨代谢标记物uNTX、sICTP及sBALP对恶性肿瘤骨转移的诊断、疗效的监测及骨相关事件的预测具有一定的价值。     

骨代谢标志物CTx、OST、BAP和PINP在乳腺癌骨转移患者血清中的变化

背景与目的:肿瘤骨转移时细胞因子作用于成骨和破骨细胞,破坏正常的骨代谢机制,导致骨代谢指标在恶性肿瘤骨转移中发生变化。本研究旨在探讨骨代谢标志物在乳腺癌骨转移患者血清中的变化,以期寻找较为可靠的临床随访指标。方法:收集51例乳腺癌骨转移患者,47例乳腺癌无骨转移患者及44例正常对照者的血清,采用放射免疫法和酶联免疫分析方法检测血清中Ⅰ型胶原羧基末端肽(β-C-terminaltelopeptide of typeⅠcollagen,CTx)、骨钙素(osteocalcin,OST)和骨特异性碱性磷酸酶(bone-specificalkaline phosphatase,BAP)及Ⅰ型胶原氨基端前肽(procollagen typeⅠN-terminal propeptide,PINP)的数值。结果:在乳腺癌骨转移组,CTx、OST、BAP和PINP的数值较对照组明显升高。各骨代谢指标与骨破坏性质、骨转移数量无明显相关。乳腺癌骨转移患者中位总生存时间为42.90个月,95%CI为38.02～47.78个月。中位骨转移发病时间(自确诊乳腺癌起)为63.65个月,95%CI为37.26～90.43个月。结论:CTx、OST、BAP和PINP的数值在乳腺癌骨转移组中明显升高,可作为临床随访的参考指标。     

血清AFP、CEA放射免疫分析对肝癌的临床诊断价值

作者选择７８例肝癌患者，其中原发性肝癌６４例，转移性肝癌１４例，行血清ＡＦＰ、ＣＥＡ放射免疫分析测定，结果揭示：血清ＡＦＰ对诊断原发性肝癌优于转移性肝癌（Ｐ＜０．０１）；血清ＣＥＡ对诊断转移性肝癌优于原发性肝癌（Ｐ＜０．０１），有助于原发性肝癌与转移性肝癌的鉴别诊断。ＡＦＰ、ＣＥＡ联合检测能降低肝恶性肿瘤的漏诊率。     

原发性肝癌患者血清肝纤维化指标检测的意义

目的 探讨原发性肝癌血清肝纤维化指标检测的意义.方法 采用ELISA法检测58例原发性肝癌、35例转移性肝癌、41例肝外恶性肿瘤患者血清HA、PcⅢ、LN和Ⅳ-C含量并与AFP作相关分析.结果 原发性肝癌组HA、PcⅢ、LN和Ⅳ-C水平明显高于转移性肝癌组和肝外恶性肿瘤组（P＜0.05或0.01）.AFP与HA、PcⅢ、LN和Ⅳ-C呈明显的正相关（γ分别为0.68、0.55、0.73、0.53,P＜0.05）.结论 肝纤维化指标与原发性肝癌关系密切,血清肝纤维化指标检测对原发性肝癌肝纤维化程度的判断、鉴别转移性肝癌有一定的价值.     

检测NTx、BSP对唑来膦酸治疗肺癌骨转移的临床意义

目的：通过检测血清NTx、BSP水平预测唑来膦酸（Zoledronic Acid）治疗肺癌骨转移的临床疗效。方法：将64例确诊为非小细胞肺癌骨转移患者使用唑来膦酸治疗。用ELISA法测定患者治疗前后血清NTx和BSP浓度。结果：使用唑来膦酸治疗后骨转移瘤好转的患者血清NTx和BSP水平显著降低（P〈0.01）;骨转移无好转者血清NTx和BSP水平变化无显著差异（P〉0.05）。结论：血清NTx、BSP的降低可以预测唑来膦酸能有效控制非小细胞肺癌骨转移,反之,无应用唑来膦酸的价值。     

胃癌患者中sIL—2R表达的临床意义

采用ＥＬＩＳＡ法检测５２例胃癌患者及２０例健康人的血清ｓＩＬ－２Ｒ浓度，结果发现：胃癌患者血清ｓＩＬ－２Ｒ水平明显高于健康对照组（Ｐ〈０．０１）。伴有转移者的ｓＩＬ－２Ｒ升高更明显，与无转移者相比，差异显著（Ｐ〈０．０１），胃癌术后ｓＩＬ－２Ｒ升高提示有复发可能。     

肝癌组织中细胞间粘着分子—1的表达与肝癌侵袭转移关系的研究

目的研究肝癌组织中细胞间粘着分子－１（ＩＣＡＭ－１）的表达与肝癌侵袭转移的关系。方法采用斑点印迹方法测定ＩＣＡＭ－１在肝癌组织、癌旁组织及正常肝组织中的表达，分析其与肿瘤生长转移状态和肿瘤特性的关系。结果肝ＩＣＡＭ－１的含量在肝癌组织中明显高于癌旁组织（Ｐ＜０．０１）和正常组织（Ｐ＜０．０１），而与肿瘤大小和有无包膜无关（Ｐ＞０．０５）。有转移组肝癌组织中ＩＣＡＭ－１的表达明显高于无转移组，而癌旁组织中两组无差别。结论ＩＣＡＭ－１有可能作为预测肝癌转移、复发及预后的指标。     

骨代谢生化指标在恶性肿瘤骨转移诊断中的价值

目的:探讨溶骨性骨代谢生化指标尿Ⅰ型胶原交联氨基末端肽(NTx)、血Ⅰ型胶原交联羧基末端肽(ICTP)定量检测诊断恶性肿瘤骨转移的价值。方法:用ELISA方法测定77例恶性肿瘤患者尿NTx和血ICTP水平。结果:骨转移组患者尿NTx和血ICTP均明显高于无骨转移组以及正常值范围(P<0.01)。骨转移患者尿NTx与血ICTP成正相关(r=0.880,P<0.01)。尿NTx诊断恶性肿瘤骨转移的灵敏度、特异度和准确度分别为82.5%、83.8%和83.2%(P<0.05)。血ICTP的灵敏度、特异度和准确度分别为87.5%、73.0%和80.6%(P<0.05)。骨转移患者尿NTx与血ICTP水平与骨转移范围成正相关(r=0.453、0.475,P<0.01),与骨痛程度无显著相关(r=0.010、0.083,P>0.05)。结论:NTx和血ICTP对恶性肿瘤患者骨转移的诊断有重要的参考意义,可协助及时诊断恶性肿瘤骨转移。     

Clinical Usefulness of Serum Carboxyterminal Propeptide of Type I Procollagen and Pyridinoline Cross-linked Carboxyterminal Telopeptide of Type I Collagen in Patients with Prostate Cancer

A study was undertaken to evaluate the clinical usefulness ofmeasurements of serum concentrations of the carboxyterminalpropeptide of type I procollagen (PICP) and the pyridinolinecross-linked carboxyterminal telopeptide of type I collagen(ICTP) as parameters of bone metastasis in patients with prostatecancer. Serum PICP, ICTP, prostate-specific antigen (PSA), andalkaline phosphatase (ALP) were evaluated in 82 patients withprostate cancer and 26 patients with benign prostatic hyperplasia(BPH). These markers were measured serially in 16 prostate cancerpatients during treatment. The serum levels of PICP, ICTP, ALP,and PSA were significantly higher in prostate cancer patientswith bone metastasis than in patients with either BPH or prostatecancer without bone metastasis. Although the rate of detectionof bone metastasis with PICP and ICTP was slightly lower thanthat with PSA determined by the receiver operating characteristiccurve, the correlation between both PICP and ICTP and the extentof disease was much higher than that of PSA. PICP and ICTP levelsvaried with ALP and PSA levels, the patient's clinical courseafter the start of endocrine therapy and the progression ofbone metastasis. The levels of PICP and ICTP did not changesubstantially in patients who developed local regrowth or lymphnode metastasis, and decreased as bone metastases respondedto radiotherapy. PICP and ICTP thus reflect the metastatic burdenin bone and are useful for monitoring the response of bone metastasisto therapy.     

Usefulness of bone metabolic markers in the diagnosis and follow-up of bone metastasis from lung cancer.

Ninety-one lung cancer patients were evaluated to determine the usefulness of bone metabolic markers in the diagnosis and follow-up of bone metastases and also to investigate their clinical usefulness as an adjunct to bone scintigraphy. Both bone resorption markers, ICTP and fDPD, and bone formation markers, Al-p, BAL, PICP and BGP, were evaluated in 47 patients with and 44 without bone metastasis. The patients with bone metastasis were classified according to the bone metastatic burden, and they were also separately classified into groups according to the course of the bone metastasis. ICTP, fDPD, Al-p and BAL were significantly elevated (P < 0.001) in patients with bone metastasis, but PICP and BGP were not. Receiver-operating characteristic (ROC) curves of these markers revealed that ICTP was most highly correlated with the diagnosis of bone metastasis. The sensitivity of ICTP (71.4%) and fDPD (61.0%) were good with high specificity. T scores of ICTP, fDPD and BAL tended to be higher at higher grades of bone metastasis. T-scores of ICTP, fDPD and BAL were elevated in the newly diagnosed cases and progressed cases, but the T-scores of ICTP and fDPD in those cases were higher than that of BAL. In the follow-up study, ICTP was well correlated with uncontrolled or controlled bone metastasis. Thus, bone resorption markers, especially ICTP, could be a good indicator of the progression and multiplicity of disease, and it could help in the follow-up and in the monitoring of therapy for bone metastasis from lung cancer.     

骨代谢指标检测在乳腺癌骨转移早期诊断中的应用价值

目的探讨骨代谢指标血清骨钙素（GBP）、Ⅰ型胶原羧基末端肽（ICTP）和尿羟脯氨酸（uHOP）早期诊断乳腺癌骨转移的应用价值。方法对86例原发性乳腺癌和20例正常女性分别采用放射免疫法测定血清BGP、ICTP和uHOP,用ECT核素骨扫描确定乳腺癌有无骨转移。结果无骨转移乳腺癌患者与正常人之间血清BGP、ICTP和uHOP水平差异无统计学意义（P〉0．05）,随访2年中32例血清BGP、ICTP和UHOP水平升高,其中29例平均在3个月后ECT核素骨扫描示骨转移,骨转移后血清BGP、ICTP和uHOP水平较转移前明显升高（P〈0．01）。结论血清GBP、ICTP和uHOP在乳腺癌骨转移的早期诊断方面有重要应用价值,且能比LECT核素骨扫描较早发现骨转移。     

Serum concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a useful prognostic indicator in multiple myeloma.

Type I collagen is the main collagen type found in mineralised bone. Specific immunoassays for PICP (carboxyterminal propeptide of type I procollagen) and ICTP (cross-linked carboxyterminal telopeptide region of type I collagen) allow simultaneous assessment of the synthesis and degradation of type I collagen in serum samples, respectively. Our aim was to find out whether these metabolites of type I collagen are useful markers for following bone turnover and evaluating treatment response in multiple myeloma, which is a good model disease of excessive osteolysis. Fifteen consecutive patients were studied before and throughout their treatment. Samples for serum PICP and ICTP were collected before starting each treatment course of melphalan and prednisolon. Response to treatment was evaluated by following the changes in M protein and bone roentgenograms. The disease was progressing in four and regressive in 11 patients, but in four of these a recurrence occurred. In nonresponders the ICTP concentration was permanently elevated despite treatment. In responders both increased or normal levels of ICTP were initially observed, but they returned to or remained in the reference interval during treatment. The ICTP concentration increased upon recurring disease. There was a strong correlation between the extent of bone lesions and ICTP. There was no correlation between ICTP and PICP, the latter mainly remaining within the reference range, a finding that suggests no change in bone formation. ICTP was a significant predictor for survival in this patient group (P less than 0.05). We conclude that ICTP is a specific and sensitive marker for bone resorption. Simultaneous use of serum ICTP and PICP offers an additional and easy means to follow bone turnover and evaluate the response to therapy in multiple myeloma.     

血清骨特异性碱性磷酸酶及Ⅰ型胶原吡啶交联终肽与乳腺癌骨转移的相关性分析

 目的　分析血清骨特异性碱性磷酸酶（BAP）和Ⅰ型胶原吡啶交联终肽（ICTP）水平在乳腺癌骨转移与非骨转移患者中的分布及其与临床特征的相关性。方法　收集乳腺癌患者血清217例，通过影像学将患者分为骨转移组（109例）和非骨转移组（108例）。应用酶联免疫吸附法测定两组血清中的BAP及ICTP水平。结果　乳腺癌骨转移组血清BAP及ICTP水平中位数分别为24.8 μg／L（7.6~213.7 μg／L）和7.0 μg／L（1.4~32.4 μg／L），高于非骨转移组的21.2 μg／L（7.3～68.8 μg／L）和4.1 μg／L（0.0～15.8 μg／L）（P＝0.003和P＝0.000），多发骨转移组的BAP及ICTP水平中位数分别为32.3 μg／L（9.4~213.7 μg／L）和7.6 μg／L（1.4～32.4 μg／L），高于单发骨转移组的18.1 μg／L（7.6～60.0 μg／L）和4.9 μg／L（1.8～10.5 μg／L）（P＝0.001和P＝0.010）。血清BAP检测诊断乳腺癌骨转移的灵敏度为45.0 %（49／109），特异度为83.3 %（90／108）；血清ICTP的灵敏度为46.8 %（51／109），特异度为84.3 %（91／108）；两者联合检测的灵敏度为61.5 %（67／109），特异度为71.3 %（77／108）。结论　检测血清BAP及ICTP诊断乳腺癌骨转移的灵敏度较低，不适合作为诊断指标。两者联合检测可以提高灵敏度，对辅助诊断有一定价值。     

恶性肿瘤患者血清骨钙素、甲状旁腺素含量与骨转移的相关性研究

目的：观察恶性肿瘤患者血清骨钙素（OC）、甲状旁腺素（PTH）的含量变化与骨转移发生、发展的关系。方法：放射免疫检测恶性肿瘤患者70例和正常健康人30例血清OC和PTH水平。结果：OC水平骨转移组高于正常对照组（P〈0．02），非骨转移组低于正常对照组（P〈0．01），骨转移组明显高于非骨转移组（P〈0．001），PTH水平骨转移组高于正常对照组（P〈0．01），非转移组与正常对照组比较无明显变化（P〉0．05），骨转移组明显高于非骨转移组（P〈0．01）。骨转移组转移病灶的数量与OC、PTH的含量成正相关。结论：血清OC、PTH对骨转移诊断具有一定临床价值。     

Evaluation of bone metabolic markers in breast cancer with bone metastasis

PURPOSE: In the present study, four bone metabolic markers were examined to clarify them meaning and clinical value in the detection of bone metastasis (BM) from breast cancer. METHODS: we examined serum carboxyterminal telopeptide of type I collagen (ICTP), tartrate resistant acid phosphatase (TRACP), total alkaline phosphatase (ALP) and urinary type I collagen cross-linked N-telopeptides (NTx) as potential markers. These bone markers were evaluated simultaneously in 156 breast cancer patients; 114 patients without metastasis (group A), 23 patients with BM (group B) and 19 patients with metastasis at sites other than bone (group C). RESULTS: The mean values of ICTP and TRACP in group B were significantly greater than those in group A. Group B consisted of the patients with varying degrees of BM and variation in their treatments. The patients in group B were divided into BM (+) and BM (++) according to hot spots in bone scan. ICTP and TRACP were elevated in BM (++) patients compared to BM (+) patients (p<0.05). The values of ICTP and TRACP of the twelve patients without treatment in group B were significantly higher than those in group A. In the treated patients of group B, the mean values of ICTP and TRACP were lower in responders and cases of stable disease than those with progression. NTx and ALP were inferior to ICTP and TRACP for clinical evaluation of BM. CONCLUSIONS: We confirmed that ICTP and TRACP might be useful markers for screening and monitoring BM in breast cancer.     

Bone metabolic markers in bone metastasis of breast cancer

Background. The efficacy and cost-performance benefit of radionuclide bone scintigraphy in monitoring metastatic bone activity remain controversial. Bone metabolic markers are now expected to play a role in the diagnosis and follow-up of bone metastasis. Methods. We investigated several bone metabolic markers in patients with breast cancer. We measured three metabolic markers of bone resorption: pyridinoline cross-linked carboxy terminal telopeptide (ICTP), C-telopeptides of type I collagen (CTx), and the free form of deoxypyridinoline (fDPD), and four metabolic markers of bone formation: procollagen I carboxy terminal peptide (PICP), total alkaline phosphatase (Al-p), bone-specific alkaline phosphatase (BAl-p), and osteocalcin (BGP) in 210 patients without and 268 patients with bone metastasis. Patients without bone metastasis were analyzed in terms of menstruation status. Patients with bone metastasis were analyzed in terms of bone metastatic burden and tumor lesion "condition" (ie, determination by X-ray and/or computed tomography and bone scan findings of new lesion, progression of disease, no change, improvement, and complete remission, according to the criteria of the International Unite Against Cancer). Results. In patients without bone metastasis, ICTP did not change with menopause. All markers other than ICTP were significantly elevated with menopause. In patients with bone metastasis, all markers, except for BGP, were significantly elevated according to metastatic bone tumor burden. Among the seven markers, ICTP showed the best receiver operating characteristic curves. ICTP also showed the best correlation to bone metastatic burden among the markers by Spearman's rank correlation coefficient. In patients stratified by "condition", ICTP, CTx, fDPD, Al-p, and BAl-p showed significant elevation in patients with progression, new lesion, and no change, while PICP and BGP showed only minimal elevation in those patients. Conclusion. Bone metabolic markers, particularly ICTP, appear to be valuable for the diagnosis of bone metastasis from breast cancer. Received: April 22, 1999 / Accepted: July 15, 1999     

Type I collagen degradation product (ICTP) gives information about the nature of bone metastases and has prognostic value in prostate cancer.

Although osteosclerotic bone metastases are characteristic of prostate cancer, mixed metastases with a lytic component are not uncommon. Type I collagen is synthesised by osteoblasts and accounts for about 90% of the organic matrix of bone. We have used new specific immunoassays for PICP (carboxy-terminal propeptide of type I procollagen) and ICTP (cross-linked carboxy-terminal telopeptide of type I collagen) which allow simultaneous assessment of the synthesis and degradation of type I collagen respectively. Forty patients with bone metastases due to prostate cancer at the time of diagnosis were investigated with these methods. Twenty-three of them had sclerotic (S) and 17 had mixed metastases with sclerotic and lytic components (S + L) as assessed by radiographs. The concentrations of PICP and ICTP in serum as well as the activity of alkaline phosphatase (AP) were increased in all patients of the S + L group, who had more aggressive bone disease and a shorter survival than the S group (P < 0.017). The ICTP level was above the reference range in half of the patients in the S group, whereas the PICP and AP levels were elevated in 35%. Of the bone markers, only ICTP was of prognostic significance (P < .05). We conclude that ICTP and PICP give information about the type and activity of the skeletal metastases. In addition, ICTP predicts prognosis.     

ICTP在诊断乳腺癌骨转移中的临床价值

目的:探讨ICTP在诊断乳腺癌骨转移中的临床价值.方法:用EIA法测定60例乳腺癌患者和23例健康体检者的ICTP血清水平.结果:乳腺癌骨转移患者ICTP血清水平较非骨转移和正常对照组显著升高,其诊断敏感性为77.8%,特异性为91.3%.多处骨转移患者血清ICTP阳性率和血清水平较单处骨转移患者显著升高且随着乳腺癌分期的升高,血清ICTP阳性率和血清水平也升高.结论:ICTP对乳腺癌骨转移患者的早期诊断,病情监测和临床分期判断具有重要意义.