碱性磷酸酶同工酶在原发性肺癌骨转移诊断中的应用

目的:探讨骨碱性磷酸酶同工酶（bone alkaline phosphatase,BALP）与原发性肺癌骨转移的相关性。方法:采用神经氨酸苷酶处理血清,琼脂糖电泳法分析测定50名健康体检者和131例原发性肺癌患者血清中的血清碱性磷酸酶（ALP）同工酶。结果:原发性肺癌组的总ALP和同工酶均高于正常对照组,原发性肺癌骨转移组的总ALP和BALP活性均显著高于对照组和无骨转移组,原发性肺癌无骨转移组的总ALP和BALP活性和对照组无显著性差异。结论:骨型ALP与原发性肺癌骨转移有一定的相关性,经神经氨酸苷酶处理血清后,采用琼脂糖电泳法分离ALP同工酶有助于临床辅助诊断原发性肺癌有无骨转移。     

血清碱性磷酸酶检测恶性肿瘤骨转移诊断价值的探讨

为了探讨血清碱性磷酸酶(ALP)在肿瘤骨转移诊断中的意义,测定365例恶性肿瘤患者(未出现骨转移)、176例肿瘤骨转移患者和246名健康成人的血清ALP活性.恶性肿瘤组血清ALP活性高于健康对照组,t=8.770,P<0.01;肿瘤骨转移组血清ALP活性高于前两者,t值分别为10.490和13.883,P值均<0.01.接受手术治疗的恶性肿瘤患者术前血清ALP活性与健康对照组差异无统计学意义,出现骨转移后则明显升高.初步研究结果提示,血清ALP活性与肿瘤骨转移有一定的相关性.定期检测恶性肿瘤患者的血清ALP活性,可以作为判断肿瘤骨转移的一个重要参考指标.中华肿瘤防治杂志,2009,16(12):953-954     

慢性粒细胞白血病碱性磷酸酶同工酶基因表达研究

目的 研究慢性粒细胞白血病(CML)患者碱性磷酸酶(ALP)同工酶基因表达特点及粒细胞集落刺激因子(G-CSF)、视黄醇的诱导作用.方法 以38名健康体检者为对照,研究44例CML患者ALP同工酶经G-CSF、视黄醇诱导前后基因表达情况.结果 CML组诱导前肝型ALP、骨型ALP均未检测到基因表达,对照组骨型ALP基因表达占93.1％；G-CSF诱导后,CML组肝型ALP(8.9％)、骨型ALP(86.7％)均检测到基因表达,且与对照组比较差异均有统计学意义(均P＜0.05),骨型ALP/(肝型ALP+骨型ALP)CML组与对照组差异无统计学意义；G-CSF合并视黄醇诱导后CML组肝型ALP(7.8％)、骨型ALP(96.7％)与对照组比较差异均有统计学意义(P＜0.05),骨型ALP/(肝型ALP+骨型ALP)两组差异无统计学意义.结论 在CML患者中存在肝型ALP、骨型ALP的基因表达缺失,G-CSF及视黄醇对CML患者ALP同工酶基因有诱导作用.     

血液病患者粒细胞中碱性磷酸酶同工酶基因表达的研究

目的：探讨粒细胞集落刺激因子（G－CSF）对正常组、真性红细胞增多症（PV）、慢性粒细胞白血病（CML）中碱性磷酸酶同工酶（ALP）基因表达的诱导作用,并寻找何种同工酶的基因表达占主导地位。方法：应用半定量反转录－聚合酶链反应（RT－PCR）,并以β-actin作内对照,检测了20例正常对照者、11例PV初治患者和23例CML初治患者ALP基因的表达,以及G－CSF对其表达的诱导。结果：诱导前,骨型ALP（BALP）基因表达在正常对照组和PV组占主导地位,PV组的ALP基因表达显著高于正常对照组,未检测到CML组ALP基因表达;G－CSF诱导后,CML组出现ALP基因表达,仍以BALP为主,显著高于正常对照组,正常对照组和PV组在诱导前后均无变化。结论：人类粒细胞主要以BALP基因表达为主;G－CSF在CML粒细胞中的ALP基因表达具有诱导作用。     

骨标志物在乳腺癌骨转移诊断与疗效观察中的作用

目的 探讨I型胶原交联羧基氨基端肽(β-Cross Laps)和总骨1型前胶原氨基端延长肽(P1NP)在乳腺癌骨转移诊断与疗效观察中的临床价值。方法 运用电化学发光法对β-Cross Laps、P1NP、CA15-3进行定量检测。57例乳腺癌骨转移患者按转移灶多少分为2组,分别为骨显像轻度异常组(Ⅰ组)36例与骨显像明显异常组(Ⅱ组)21例。结果 骨转移组β-Cross Laps、P1NP两种血清标志物较无骨转移组与对照组明显升高,差异具有统计学意义(P＜0.01),且治疗后两种指标明显低于治疗前水平(P＜0.05),随转移灶增加两种标志物水平也有升高趋势,差异具有统计学意义(P＜0.01)。而各组间及治疗前后CA15-3无显著变化(P＞0.05)。骨标志物β-Cross Laps、P1NP对乳腺癌骨转移的诊断灵敏度分别达到71.25%与64.05%,特异性分别达到88.00%与81.99%,均高于骨显像所显示结果的50.32%和61.17%。结论 血清骨标志物β-Cross Laps、P1NP水平可以反映乳腺癌骨转移患者病情变化,并可以运用于疗效监测,有较好的临床应用价值。     

唑来膦酸钠对绝经后乳腺癌患者骨代谢影响结果分析

目的：通过观察唑来膦酸钠对绝经后乳腺癌患者骨代谢影响,探讨唑来膦酸钠在早期预防乳腺癌患者发生骨代谢障碍及抑制骨转移中的作用。方法：85例绝经后乳腺癌患者均手术治疗,且术后常规行6个疗程的化疗,无骨转移病例。对照组：28例化疗后接受中药治疗;来曲唑组：30例化疗后继续服用来曲唑2．5mg／d;来曲唑＋唑来膦酸钠组：27例患者化疗后除服用来曲唑2．5mg／d外,使用唑来膦酸钠注射液4mg＋生理盐水100ml,静脉滴注15min,每4周为1个疗程。6个月后应用双能x线骨密度仪对三组乳癌患者腰椎、股骨近端骨密度（BMD）进行测定,用SPETCT行全身核素骨显像检查,使用全自动生化仪器测定血清碱性磷酸酶（ALP）、血钙（Ca）、血磷（P）等生化指标,用免疫组化方法测定雌激素（E2）,对三组患者治疗前后各项指标分析比较。结果：治疗后来曲唑组与对照组病人的BMD、E2、血清Ca、P指标比较,均明显降低（P〈0．05）、ALP明显上高（P〈0．05）;来曲唑＋唑来膦酸钠组与来曲唑组比较,BMD、血清Ca、P指标明显升高（P〈0．05）,ALP降低（P〈0．05）、E2未见明显变化（P〉0．05）;来曲唑＋唑来膦酸钠与对照组比较,ALP、E2指标明显降低（P〈0．05）,BMD明显升高（P〈0．05）,血清Ca、P未见明显变化（P〉0．05）。与对照组比较唑来膦酸钠组的骨转移发生率明显降低（P〈0．05）。结论：唑来膦酸钠对接受来曲唑治疗引起的骨代谢障碍早期防治疗效明显,且对骨转移发生有明显抑制作用。     

BSP和PTHrP的联合检测对乳腺癌骨转移临床意义的研究

目的:探讨骨唾液蛋白(BSP)和甲状旁腺相关蛋白(PTHrP)的联合检测对乳腺癌骨转移的临床意义.方法:乳腺癌87例患者,分为骨转移组40例和无骨转移组47例.应用免疫组织化学法检测石蜡包埋标本BSP和PTHrP的表达.结果:BSP和PTHrP在骨转移组的阳性表达均明显高于无骨转移组(x2值分别为8.47和10.49,P均<0.01),且强阳性表达也均高于后者(x2值分别为9.18和11.05,P均<0.05);同时两者在骨转移组的阳性表达与无转移组和骨外转移组之间比较,差异有统计学意义(P<0.01),而后两组间阳性表达差异无统计学意义(P>0.05).Cox比例风险回归模型分析结果发现,乳腺癌组织中BSP和PTHrP的高表达是预测骨转移的主要危险因素(P<0.01),其相对危险度分别为1.293和1.348.Log-rank生存曲线分析结果显示,在乳腺癌患者中BSP和PTHrP高表达者的累积生存概率均明显低于BSP和PTHrP阴性表达组,P<0.05.结论:BSP和PTHrP的过表达是早期预测乳腺癌骨转移的良好标志,并可作为评估乳腺患者的一项重要的预后因子.     

联合检测血清NTx和BSP对乳腺癌和肺癌骨转移的意义

摘 要 目的: 探讨骨代谢生化指标血清Ⅰ型胶原交联氨基末端肽（Ntelopeptide of type Ⅰ collagen，NTx）和骨涎酸蛋白(bone sialoprotein, BSP)的检测对肺癌和乳腺癌骨转移的临床意义。方法：选择2006年1月至2006年7月长海医院肿瘤科经病理确诊的肺癌或乳腺癌患者105例，分为两组，其中骨转移组50例，无骨转移组55例。应用ELISA法检测患者血清NTx和BSP浓度。结果：骨转移组患者血清NTx和BSP水平均明显高于无骨转移组（P<0.01）。NTx诊断骨转移的灵敏度和特异度分别为90.0％和67.3％，BSP诊断骨转移的灵敏度和特异度分别为84.0％和70.9％。临床发生骨相关事件（skeletal related event，SRE）的骨转移患者，血清NTx水平明显高于未发生SRE的骨转移患者（P<0.05）。在6~13个月随访期内，21例患者确诊了新发骨转移；采用Cox比例风险回归模型分析，血清NTx浓度升高提示骨转移发生的相对危险度为1.127；乳腺癌患者血清BSP增高是唯一预测骨转移的危险因素（P<0.05），其相对危险度为1.058。随访期共有33例患者死亡；无论肺癌还是乳腺癌，血清BSP增高患者的累积生存率均明显低于血清BSP正常组（P<0.05）。结论：血清NTx和BSP是诊断肺癌和乳腺癌骨转移的重要参考指标，其水平的增高是预测骨转移发生的高危因素；BSP可能是肺癌和乳腺癌患者独立预后指标。     

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。     

BSP在原发性乳腺癌组织中的表达对预测术后骨转移的临床意义

目的:探讨BSP在原发性乳腺癌组织中的表达对预测术后骨转移的临床意义.方法:用免疫组织化学SP法测定70例原发性乳腺癌石蜡标本中BSP的表达,及ER、PR、C-erb-B2表达情况.结果:1)BSP在骨转移组表达明显高于无骨转移组(无转移组 骨外转移组)(P＜0.01),且强阳性表达高于后者(P＜0.05);同时,骨转移组与无转移组和骨外转移组之间阳性表达均有差别(P＜0.05;P＜0.01),而后两组间阳性表达无统计学差异(P＞0.05).2)BSP的表达在Ⅱ期及Ⅲ期患者组间有差异(P＜0.05),但与患者年龄及ER、PR、C-erb-B2状态,肿块大小,病理类型及淋巴结转移数目均无相关(P＞0.05).结论:在原发性乳腺癌组织水平上,BSP是早期预测术后骨转移的良好标志物.     

Clinical evaluation of serum osteocalcin in patients with bone metastasis of breast cancer

Bone metastasis is one of the characteristic behavior of recurrent breast cancer. Usually, X-ray detect and/or bone scintigraphy are used to evaluate bone metastasis. However, false positive cases are occasionally encountered in these modalities. This is a report of the results from the measurement of serum osteocalcin (OC) in breast cancer with bone metastasis. OC is one of the protein dependent on Vitamin K. The results were as follows: 1) Serum levels of OC in 56 patients with primary breast cancer were measured. The mean level of serum OC was significantly higher than that in patients with benign breast disease. But the comparisons in each stage were not statistically significant. 2) The mean serum OC level in patients of primary breast cancer with bone metastasis was higher than that in breast cancer without bone metastasis (p less than 0.05). This was remarkable in the patients of recurrent breast cancer (p less than 0.01). 3) Serum OC levels in bone metastasis patients were increased in group with normocalcemia, while it was normal or decreased in that with hypercalcemia. There was no significant correlation between either serum OC and ALP values, or between serum OC and serum Ca values. The slight positive and reverse correlation were observed between OC and ALP, OC and sCa, respectively. 4) In many cases with bone metastasis, serum OC levels were elevated before bone lesions were detected by bone scintigraphy. 5) In advanced stage of the patients with bone metastasis and hypercalcemia, serum OC level decreased. The increased level of serum OC was maintained when high dose of calcitonin was administered.     

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.     

骨转换标志物在非小细胞肺癌骨转移临床应用中价值的研究

背景与目的:骨转移导致骨质破坏,可引起骨转换标志物(bone turnover markers)水平的改变;因此,本研究旨在探讨骨转换标志物在非小细胞肺癌(non-small cell lung cancer,NSCLC)骨转移诊断及病情评价方面的应用价值.方法:定量检测76例NSCLC骨转移患者血清中碱性磷酸酶(alkaline phosphatase,AKP)、β-Ⅰ型胶原羧基端肽(β-C-terminal telopeptide of type Ⅰ collagen,β-CTx)、骨钙素(osteocalcin,OST)和骨特异性碱性磷酸酶(bone-specific alkaline phosphatase,BALP)水平,并与44例健康人群进行对照.结果:骨转移组患者血清中AKP、β-CTx和BALP水平均明显高于正常对照组.各骨转换标志物之间有很好的相关性,BALP和OST的表达水平与骨转移程度呈正相关性.β-CTx表达水平较高和BALP表达水平较低的患者发生病理性骨折可能性增加.结论:骨代谢标志物在NSCLC骨转移患者诊断及病情判断方面有重要的参考价值,在临床上有广泛的应用前景.     

肺鳞癌骨转移因素分析

目的:分析肺癌诊断因素与肺鳞癌全身骨显像骨转移之间的关系。方法:回顾性分析185例肺鳞癌患者的全身骨显像及肺癌有关的肿瘤标志物,以全身骨显像为诊断骨转移的金标准。单因素方差分析和ROC工作曲线下面积比较,得出肺癌肿瘤标志物与肺鳞癌全身骨显像骨转移之间的关系。结果:单因素方差分析结果:NSE、CEA、ProGRP、ALP,均P＞0.05,差异无统计学意义,与骨转移无关;CYFRA21-1、SCC、CA125,均P＜0.05,差异有统计学意义,与骨转移有关;ROC受试者工作曲线结果:CEA(AUC=0.542,P=0.395)、ProGRP(AUC=0.577,P=0.116)、ALP(AUC=0.506,P=0.900),AUC均近于0.5,诊断准确性不高,且其P＞0.05,差异无统计学意义;CYFRA21-1(AUC=0.687,P=0.000)、NSE(AUC=0.679,P=0.000)、SCC(AUC=0.638,P=0.005)、CA125（AUC=0.660,P=0.001）,AUC近于0.7,诊断准确性较高,均P＜0.05,差异有统计学意义,与骨转移有关。结论:CEA、ProGRP、ALP与骨转移无关,不具有对肺鳞癌骨转移的预测和诊断意义;CA125、CTFRA21-1、NSE、SCC与骨转移有关,对肺鳞癌骨转移具有预测和诊断意义。     

Study of bone metabolism for breast cancer by MD (microdensitometry) method

Bone is one of the involved organs of distant metastasis in breast cancer. We examined bone metabolism by microdensitometry (MD) method in 94 patients with breast cancer (40 with bone metastasis and 54 without it) and 10 with benign breast diseases. There was no significant difference among the three groups in the background factors of menopausal status and hormone receptors status. MCI, GSmin, sigma GS/D and bone pattern by MD method in breast cancer patients with bone metastasis were significantly lower than those in the other groups. There were slight reverse correlation between sigma GS/D and serum ALP. MCI and sigma GS/D indices corrected by ages were also significantly lower in bone metastasis (p less than 0.01). These indices in most of the patients with bone metastasis gradually decreased as the lesion progressed. The results revealed that microdensitometric analysis of bone metastasis for breast cancer was of use for the diagnosis and evaluation of therapeutic effect in the follow-up study.     

Biochemical markers of bone turnover in breast cancer patients with bone metastases: a preliminary report

BACKGROUND: Some biochemical markers of bone turnover are expected to reflect the disease activity of metastatic bone tumor. In the present study six biochemical markers were evaluated to determine appropriate markers for the detection of metastatic bone tumors from breast cancer (BC). METHODS: A panel of bone turnover markers was assessed in 11 normocalcemic patients with bone metastases from BC and in 19 BC patients without clinical evidence of bone metastases. Bone formation was investigated by measuring serum bone isoenzyme of alkaline phosphatase (BALP), osteocalcin (OC) and carboxy-terminal propeptide of type I procollagen (PICP): Bone resorption was investigated by measuring serum carboxy-terminal telopeptide of type I collagen (ICTP), fasting urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr). RESULTS: PICP was influenced by age and menopausal status. Significant correlations were observed between each of bone turnover markers except between BALP and OC. The mean levels of the six bone turnover markers were higher in patients with bone metastases than in those without them and significance was observed except for OC. The best diagnostic efficiency by receiver-operating characteristic (ROC) analysis was provided by ICTP followed by Pyr or D-Pyr, BALP, PICP and OC and significance was observed between ICTP and OC. Multiple logistic regression analysis adjusted by age revealed that the only significant marker related to bone metastases was ICTP. CONCLUSIONS: Serum ICTP appears to be the leading marker of bone metastases from BC. However, to reveal the clinical usefulness of these markers, further examination will be needed to account for the ease and cost-effectiveness of the measurements.     

SPECT骨显像联合血清碱性磷酸酶检测评估肺癌患者骨转移负荷的价值

目的:探讨SPECT骨显像结合碱性磷酸酶(ALP)评估初诊肺癌骨转移负荷的价值.方法:109例初诊未治疗肺癌患者行99Tcm-MDP SPECT全身骨显像,其中发生骨转移51例,无骨转移58例;根据骨显像发现骨病灶数目及受累情况,将骨显像分为0-3级,并检测血清ALP水平;比较各组骨显像分级ALP水平,进行相关分析.结果:109例初诊肺癌患者,转移率46.8％ (51/109);骨显像1-3级患者存在外周血ALP不同程度增高,波动范围127 ～ 782 U/L;0-3级各组ALP检测值分别为[(110.26 ±42.13) U/L,58例]、[(138.85±86.72) U/L,16例]、[(267.84±147.52) U/L,15例]、[(481.46 ±289.73) U/L,20例].各组ALP水平除骨显像0级组与1级组之间差异无统计学意义(t=1.346,P＞0.05);其它各组随着骨显像分级升高,ALP值逐渐增高,且各组间差异有统计学意义(P＜0.05).血清ALP水平与骨显像分级呈正相关(r=0.945,P＜0.01).骨显像1级组中有4例患者,每例有2个异常浓聚灶,其中1个病灶经CT或MRI确定为骨转移,但另外1个病灶不能确定是否骨转移;2例患者ALP升高,2例ALP正常;随访半年,2例ALP正常患者的病灶排除骨转移,另外2例ALP升高患者的病灶确定为转移.结论:SPECT骨显像结合初诊肺癌ALP水平对评估肺癌骨转移负荷存在一定价值;值得临床重视与应用,以合理地肺癌分级等.     

Visceral metastasis in 135 cases of breast cancer: evaluation at autopsy

We examined the distribution and frequency of metastasis in 135 breast carcinoma cases autopsied between 1946 and 1981 at the Cancer Institute, Tokyo, and studied the relationship between the results and various factors such as histological type, patient age, therapy and clinical course. Breast carcinoma metastasizes more widely and more frequently than other malignant tumors; there is a high rate of metastasis to the bone, adrenals, opposite breast, and thyroid. Medullary tubular carcinoma metastasizes more highly than other histological types. The frequency of metastasis is higher in the younger age group and in patients irradiated to the primary sites. There is little correlation between the frequency of metastasis and total duration.