尿吡啶酚和氧吡啶酚在恶性肿瘤骨转移中的临床意义

目的　评价尿吡啶酚和脱氧吡啶酚对恶性肿瘤骨转移患者的临床意义。方法　采用ELISA方法检测了 2 6例局限性恶性肿瘤、3 5例进展期肿瘤骨转移阴性和 3 4例骨转移阳性的尿吡啶酚和脱氧吡啶酚水平。结果　进展期肿瘤尿吡啶酚和脱氧吡啶酚水平明显高于限局性肿瘤 (P <0 .0 5 ) ;进展期肿瘤骨转移阳性尿吡啶酚和脱氧吡啶酚水平又明显高于骨转移阴性 (P <0 .0 5 )。结论　尿吡啶酚和脱氧吡啶酚在评价进展期肿瘤骨转移和骨吸收中发挥作用。     

尿吡啶酚、尿脱氧吡啶酚、尿氨基末端肽在转移性骨肿瘤临床随访价值的应用研究

[目的]探讨尿吡啶酚（uPvd）、尿脱氧吡啶酚（uDpd）、尿氨基末端肽（uNTx）在肿瘤骨转移患者随访中的应用价值。[方法]晚期肿瘤骨转移患者46例，分别按肿瘤内科治疗原则选用化疗、双膦酸盐治疗、姑息治疗。治疗开始前测定基线uPyd、uDpd、uNTX水平，以后于第1、3个月及以后每3个月检测。记录骨相关不良事件（SItE）。[结果]在1年随访期间，骨转移患者uPyd、uDpd、uNTx水平在含双膦酸盐治疗后1个月有明显下降（P〈0．01）。SRE发生时uNTx测定水平与SRE发生前最近一次uNTx测定水平比较有统计学差异（P〈0．01），Lg（uNTx／Cr）从2．24±0．12升至2.31±0．13。[结论]uPyd、uDpd、uNTx水平能及时反映抗骨转移治疗特别是双膦酸盐治疗的效果；uNTx水平在SRE发生时有升高趋势，能提示骨病变的进展。     

骨代谢生化指标和恶性肿瘤骨转移不同临床表现的关系

目的探讨骨代谢生化指标尿吡啶酚(uPYD)、尿脱氧吡啶酚(uDPD)、血清骨特异性碱性磷酸酶(sBAP)、血清骨钙蛋白(sBGP)和恶性肿瘤骨转移临床表现的关系。方法采用ELISA方法对99例进展期骨转移阳性肿瘤进行uPYD、uDPD、sBAP、sBGP的浓度水平检测。结果uPYD和uDPD、sBAP和sALP之间显著相关,肿瘤骨转移重度疼痛、无痛和轻度疼痛之间uPYD、uDPD、sALP水平有显著性差异(P<0.05),uDPD、sBAP和sALP水平在不同的骨转移程度有显著性差异(P<0.05),sBAP和sALP水平在不同的骨转移数目有显著性差异(P<0.05)。结论骨转移时uPYD和uDPD、sBAP和sALP之间显著相关,uPYD、uDPD、sBAP水平和骨痛明显相关,uDPD、sBAP水平和肿瘤骨转移程度、骨转移数目明显相关。骨代谢生化指标uPYD、uDPD、sBAP和骨转移临床表现的关系对肿瘤骨转移的病情判断有一定临床意义。     

尿脱氧吡啶酚在肺癌骨转移中的临床意义

采用全自动免疫化学光法对正常人、肺癌不伴骨转移、肺癌伴骨转移分别进行尿脱氧吡啶酚的测定。尿DPD/cr在正常人、肺癌不伴骨转移、肺癌伴骨转移中的水平分别为 3 85± 2 0 0nmol/mmol ;6 30± 2 0 5nmol/mmol ;13 6 5±3 15nmol/mmol ;肺癌患者伴骨转移者尿DPD/cr明显高不伴骨转移者和正常对照组。脱氧吡啶酚对肺癌骨转移早期诊断是一个灵敏的骨代谢指标     

UNTX水平检测在监测肺癌骨转移中的价值

目的 检测与分析肺癌骨转移瘤患者尿I型胶原交联氨基末端肽（uNTX）水平,评价其与骨转移病情发展和疗效的关系。方法 研究对象为正常组33例;肺癌组31例;肺癌骨转移组30例。分别测定3组uNTX水平,同时进行尿脱氧吡啶酚及血清AKP活性和Ca2＋浓度的测定,肺癌骨转移组进行了治疗前后uNTX水平对比。结果 肺癌骨转移组uNTX水平明显高于其他两组,其治疗前后uNTX水平也有显著性差异。结论 肺癌骨转移时uNTX水平会发生异常,uNTX水平与骨转移的发生呈正相关,uNTX敏感度高于尿脱氧吡啶酚及血清AKP活性和Ca^2＋浓度,在预测肺癌骨转移瘤和监测病变进程中有重要临床价值。     

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     

乳腺癌骨转移患者溶骨性骨代谢指标与治疗效果的关系

目的 探讨特异性的溶骨性骨代谢指标血I型胶原吡啶交联羧基末端肽(sICTP)、尿I型胶原吡啶交联氨基末端肽(uNTx)和尿吡啶酚(uPyd)与乳腺癌骨转移患者治疗反应的关系.方法 应用酶联免疫吸附试验(ELISA),测定120例乳腺癌患者的sICTP、uNTx和uPyd,比较其在骨转移和无骨转移患者中浓度的差别,并对乳腺癌骨转移患者进行随访,比较患者治疗前后sICTP、uNTx和aPyd指标与治疗效果的关系.结果 骨转移组患者的sICTP、uNTx和uPyd水平均明显高于无骨转移组(P<0.01),56例乳腺癌骨转移患者的sICTP、uNTx和uPyd指标间两两相关(均r>0.5,P<0.01).获得随访的45例乳腺癌骨转移患者中,临床受益组25例,sICTP、uNTx和uPyd治疗3个月后明显下降(P=0.025,P<0.001,P<0.001).病情进展组20例,治疗3个月后,sICTP、uNTx和uPyd无明显变化(P>0.05);而病情进展后,sICTP、uNTx和uPyd明显升高(P=0.011,P=0.002,P=0.002).Logistic回归分析结果显示,uPyd和uNTx治疗后降低的患者治疗收益的概率增加(OR=17.0,P=0.019;OR=16.7,P=0.015),而治疗后sICTP指标下降与治疗受益无关(P=0.841).结论 sICTP、uNTx和uPyd可作为乳腺癌骨转移患者评价疗效和转归监测的辅助指标.     

博宁对骨转移患者骨吸收标志的影响

目的：探讨博宁对骨转移患者骨吸收标志的影响。方法：临床确诊为骨转移患者２４例,一次性接受博宁９０ｇｍ静点,观察治疗前及后７天骨吸收标志的变化。结果：治疗前尿钙、尿吡啶酚和脱氧吡啶酚较正常值分别为２５％,７１％和１００％患者升高。治疗后第７水钙、尿吡啶酚和脱氧吡啶较治疗前均明显下降,三项指标较治疗前分别下降了５９％,６２％和６０％,血钙治疗后也有明显下降,而血磷治疗前后无明显变化。     

转移相关基因CD44v6在胃癌中的表达意义

目的：探讨转移相关基因ＣＤ４４ｖ６与胃癌某些生物学行为的关系。方法：采用免疫组化ＳＰ法对４２例进展期胃癌进行标记分析。结果：ＣＤ４４ｖ６阳性表达率肠型胃癌（７０．８３％）明显高于弥漫型胃癌（３３．３３％）（Ｐ〈０．０５）;淋巴结转移组（８２．３５％）明显高于无淋巴结转移组（３６．０％）（Ｐ〈０．０１）;ＣＤ４４ｖ６阳性率与肿瘤大小无关（Ｐ〉０．０５）;ＣＤ４４ｖ６阳性表达的不同病理分型的胃癌中淋巴     

非小细胞肺癌骨转移规律和影响因素分析

目的 探讨非小细胞肺癌的骨转移规律和影响因素。方法 对６３８例非小细胞肺癌患者的骨转移情况进行了统计分析。结果 非小细胞肺癌骨转移率为３５．３％。多发转移者２０１例，全组平均病灶３．４个。骨转移的部位以胸部最常见，其它依次为脊柱、骨盆、肢体和颅骨，各组间比较有非常显著差异（Ｐ〈０．００５）。腺癌和腺鳞癌骨转移率明显高于鳞癌（Ｐ〈０．００５）。细胞分化程度较低者骨转移率明显增高（Ｐ〈０．００５）。Ⅲ     

Urine calcium and deoxypyridinoline in assessment of response to local radiation therapy for metastatic bone disease

To evaluate the predictability of urine calcium (Ca+2) and deoxypyridinoline (DPD) in the assessment of response to palliative radiation therapy (RT) for metastatic bone disease. Forty-two patients with osteolytic bone metastases from breast or lung primaries were enrolled in this study. Serial urine Ca+2 and DPD measurements were performed before RT, six weeks, and twelve weeks afterwards. All eligible patients received a total of 30 Gy RT in 3 Gy daily fractions. Pre-irradiation mean urine Ca+2 and DPD levels were 16 +/- 3.7 g/micromol/dL, and 89.2 +/- 61 pmol/micromol crea. Both were significantly higher than normal range. A significant correlation between pre-irradiation Ca+2 (r = 0.6, p < 0.001), DPD (r = 0.8, p < 0.001) levels and the extent of bone metastases were detected. Thirty-six patients (Group I) were alive without disease progression outside the radiation portal. Urine Ca+2 and DPD levels demonstrated a significant and progressive decrease following RT in Group I patients (p < 0.001). Clinical and radiological evaluation revealed occurrence of new bone metastases in six patients (Group II), with concurrent significant increase in concentrations of urine DPD and Ca+2 (p = 0.006 for Ca+2 and p = 0.009 for DPD, respectively). Urine Ca+2 and DPD levels can be used for assessment of response of bone to local irradiation, and are able to predict further progression of bone metastases in cancer patients.     

Role of biochemical indices as metastatic markers in patients with prostatic cancer invading skeleton

Biochemical markers of resorption and formation of bone tissue (piridinoline-PD, desoxypiridinoline-DPD and alkaline phosphatase-AP, respectively) were measured in blood serum and urine of 41 prostatic cancer (PC) patients with metastases to the bones and 24 PC patients free of such metastases as well as of 40 healthy males and 11 males with benign prostatic hyperplasia (BPH). It was found that PD, DPD levels, general AP activity and activity of its bone fraction were significantly higher in PC patients with bone metastases than in the others (p < 0.001). The former had a significantly higher percent of peptide-bound and lower percent of free forms of PD and DPD (p < 0.001) vs patients without metastases and controls. Higher biochemical serum and urine indices in PC patients with bone metastases reflect enhanced intensity of both formation and resorption of bone tissue in PC with bone metastatic lesions. Therefore, it is possible to use PD, DPD and AP values in diagnosis and monitoring of metastatic skeletal destruction in PC.     

The biochemical markers of bone remodeling in cancer patients with skeletal involvement

The report discusses a study of pyridinoline (Pyd) and deoxypyridinoline (Dpyd) as biochemical markers of bone resorption as well as total bone alkaline phosphatase level (APh) and that of its bone fraction as criteria of osteogenesis in skeletal lesions in breast, prostate and lung cancer and multiple myeloma. The investigation established a significantly enhanced Pyd and Dpyd excretion with urine and increased blood-serum APh levels in skeletal cancers (n = 271) as compared with healthy subjects (n = 173) and patients without bone metastases (n = 94). A case has been made for determination of total excretion of Pyd crosslinks of collagen to diagnose bone metastases. Most pronounced hyperenzymemia was found in prostate cancer which points to the leading role of APh as a bone metastasis marker. Pyd and Dpyd excretion and APh levels were significantly higher among patients multiple metastases with than in those with single bone metastases. The universality of pyridinoline crosslinks as skeletal damage markers has been confirmed by establishing a significant correlation between drug and therapeutic effect for Pyd and Dpyd only, in patients receiving ibandronate.     

Markers of bone resorption in patients treated with pamidronate

Pyridinoline (PYD), deoxypyridinoline (DPD), and N-telopeptide (NTX) are markers of bone resorption. In cancer patients with bone metastases, NTX is more often elevated than either of the pyridinolines. Bisphosphonates inhibit osteoclasts and their treatment decreases skeletal complications of malignancy. The aim of this study was to correlate urinary PYD, DPD, and NTX levels with clinical events in patients receiving pamidronate. 25 cancer patients with lytic bone disease were treated with monthly pamidronate combined with endocrine or chemotherapy; 27 others were on placebo. Twenty-four hour urines were collected at baseline, 1, 3 and 6 months. NTX values were determined by enzyme-linked immunosorbent assay (ELISA); PYD and DPD values were determined by reverse phase high performance liquid chromatography (HPLC). Two hour urines were also collected weekly for 21 patients. The greatest difference as a result of pamidronate treatment was observed in NTX values. Maximum suppression was achieved 2 weeks after treatment. Of the 25 patients who received pamidronate, 21 had initially elevated NTX values. 12 of the 21 finished with normal NTX values, whilst 9/21 had NTX values which remained abnormally elevated. The proportions of patients with fractures between these two subgroups approached statistical significance (P = 0.07) while the proportions with bony disease progression were significant (P = 0.03, Fisher's exact test). Measuring NTX levels appears useful in monitoring bisphosphonate therapy of bone metastases. The goal of treatment should be to normalise NTX excretion.     

Serum bone sialoprotein as a marker of tumour burden and neoplastic bone involvement and as a prognostic factor in multiple myeloma

To test the potential of immunoreactive BSP, a non-collagenous bone matrix component, as a clinical guide in patients with plasma cell dyscrasias, serum BSP concentrations were measured in 62 patients with newly diagnosed multiple myeloma (MM) followed over a period of 4 years, in 46 patients with monoclonal gammopathy of undetermined significance (MGUS), in 71 patients with untreated benign vertebral osteoporosis (OPO), and in 139 healthy adults. Results were compared with clinical and laboratory data, including serum osteocalcin (OC), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone turnover. In MM, serum BSP, and urinary PYD and DPD were higher than in healthy controls and in MGUS or OPO (P< 0.001). BSP levels correlated with the bone marrow plasma cell content (r = 0.40, P< 0.001), and serum beta2-microglobulin (r = 0.31, P < 0.01). The differentiation of MM from healthy controls and from MGUS or OPO was highest for BSP. After chemotherapy, BSP reflected the response to treatment and correlated with the change in monoclonal protein (r = 0.55, P< 0.001). MM patients with normal baseline BSP levels survived longer than patients with initially elevated BSP values (P< 0.001, log rank test). Only serum monoclonal protein and BSP were independent predictors of survival. We conclude that in MM, BSP levels are associated with skeletal involvement and tumour cell burden. The quantification of serum BSP may be a non-invasive method for the diagnosis and follow-up, and may improve the prognostic value of conventional staging in MM.     

Serum concentration of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen in patients with metastatic breast cancer

The serum concentration of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) was examined in 83 patients with metastatic breast cancer. ICTP levels were significantly higher in patients with bone metastases than in those without bone metastasis. In patients with bone metastasis, significantly higher ICTP levels were observed in those with multiple lesions than in those with a solitary lesion and these levels reflected therapeutic response. Sequential monitoring of ICTP revealed that this elevation was correlated with disease progression. Combined with imaging studies, monitoring of ICTP appears to offer additional information for detection of bone metastasis and evaluation of therapeutic response to bone metastasis.     

Diagnostic value of bone-turnover metabolites in the diagnosis of bone metastases in patients with lung carcinoma

BACKGROUND: Several biochemical markers of bone formation and bone resorption have been developed recently. The authors evaluated the usefulness of new biomarkers, such as urinary deoxypyridinoline (D-PYD), serum pyridinoline cross-linked C-telopeptides of Type I collagen (1CTP), and urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), in the assessment of bone metastases in patients with lung carcinoma. METHODS: The serum concentrations of 1CTP and the urinary concentrations of D-PYD and NTx were measured in 100 lung carcinoma patients, of whom 20 patients had bone metastases and 80 patients did not. Receiver operating characteristic (ROC) curves were drawn for these markers to compare their usefulness in detecting bone metastases originating in lung carcinoma. RESULTS: Urinary concentrations of NTx in patients with bone metastases were significantly greater than in patients without bone metastases (147.1 +/- 129.3 pmol bone collagen equivalents [BCE]/micromol Cr vs. 47.2 +/- 29.9 pmol BCE/micromol Cr; P < 0.0001). Urinary concentrations of D-PYD in patients with bone metastases also were significantly greater than in patients without bone metastases (10.0 +/- 3.6 BCE/micromol Cr vs. 6.6 +/- 2.2 pmol BCE/micromol Cr; P = 0.0001). No significant difference was observed in serum concentrations of 1CTP between patients with and without bone metastases. A moderate but significant correlation was seen between NTx and D-PYD (correlation coefficient [R] = 0.435; P < 0.0001) and between D-PYD and 1CTP (R = 0.525; P < 0.0001). NTx had a better ROC curve than D-PYD and 1CTP (the areas under the ROC curve were 0.84, 0.79, and 0.62, respectively). Using the threshold of 62.5 pmol BCE/micromol Cr for NTx, sensitivity, specificity, and accuracy were 0.800, 0.737, and 0.750, respectively. CONCLUSIONS: In the current study, the measurement of NTx appeared to be most useful as a marker of bone metastases in patients with lung carcinoma.     

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.     

Preliminary results of the use of urinary excretion of pyridinium crosslinks for monitoring metastatic bone disease.

The collagen crosslinks, pyridinoline and deoxypyridinoline, are recently described markers of the rate of bone resorption. The urinary excretion of these compounds, expressed as a ratio to urinary creatinine, has been measured using ion-pair reversed phase high-performance liquid chromatography in 20 patients receiving oral pamidronate for bone metastases from breast cancer. Before treatment the ratio of pyridinoline and deoxypyridinoline to creatinine in urine (UPCR and UdPCR respectively) were each above normal in 16/20 (80%) patients. Urinary calcium excretion (UCCR) was elevated in 15/20 (75%). There was a strong correlation between UPCR and UdPCR, but neither of the crosslink measurements correlated well with UCCR. Urinary excretion of all three indices of bone resorption fell significantly during pamidronate treatment. The median values after 4 weeks treatment were 63% of baseline for UPCR, 45% for UdPCR and 26% for UCCR. From this preliminary study urinary pyridinoline and deoxypyridinoline excretion appear to be promising markers of bone resorption in advanced malignancy. Their role in response assessment and the advantages over UCCR measurements merit further study.