Correlation between bone scan findings and collagenase activities in patients with breast cancer

RATIONALE AND OBJECTIVES: This study correlates nuclear bone scan findings and measurements of type IV collagenases for the evaluation of bony metastasis in patients with proven breast cancer. METHODS: The authors retrospectively evaluated the final diagnosis of a bone scan and the results of an immunohistochemical staining for 92 kDa and 72 kDa type IV collagenases in, respectively, 30 and 30 patients with metastatic breast cancer, and, respectively, 27 and 26 patients with primary breast cancer. The immunohistochemical staining was performed with tissue specimens obtained from a primary or metastatic breast tumor lesion. The amounts of the enzyme were graded from 0 to 4 and scored by multiplication with the percentage of tumor cells. The confidence of bone scan interpretation also was scored from 1 to 5 with increasing probability. RESULTS: There was a significant difference in enzyme scores between patients with and without metastases. Patients with < 170 92 kDa (26 of 27), 72 kDa (26 of 26) type IV collagenase, showed no active bony, lung, or liver metastases. However, there were variable bone scan findings in patients with a > 200 enzyme score. CONCLUSIONS: Bone scan provides no additional benefit in breast cancer patients with a type IV collagenase score of < 170. A bone scan is necessary to confirm, localize, or followup bony metastases in patients with an enzyme score of > 200.     

Diagnostic validity of bone metabolic markers for bone metastasis

We measured bone resorption markers in tumor patients with and without bone metastases and evaluated the diagnostic validity of these biochemical parameters in the diagnosis of neoplastic bone involvement. On the basis of radiography and bone scintigraphy findings, subjects were divided into 3 groups, 83 patients without bone metastases (META(-)), 22 patients with 1 or 2 bone metastases (META(+)) and 22 patients with more than 3 bone metastases (META(++)). Among the biochemical markers, urinary pyridinoline (PYR), circulating C-terminal telopeptide of type I collagen (ICTP) and urinary N-terminal telopeptide of type I collagen (NTx) were especially sensitive and specific and increased significantly not only in META(++) but also even in META(+). The efficacy of several bone metabolic markers in differentiating between patients with and without bone metastases was evaluated by receiver-operating characteristic (ROC) analysis, and PYR, ICTP and NTx were proved to have high diagnostic validity (area under the ROC curve; 0.75 for PYR, 0.77 for ICTP and 0.77 for NTx). Furthermore, their odds ratios showed significantly high values for both META(+) and META(++)(to META(++); 7.91 for PYR, 5.33 for ICTP and 5.70 for NTx). On the other hand, urinary deoxypyridinoline (DPYR) and serum total alkaline phosphatase (ALP) showed relatively low sensitivities, the odds ratio of ALP in particular being insignificant. In conclusion, several bone metabolic markers were proved to be useful in the diagnosis of bone metastases in patients with malignancies, particularly PYR, ICTP and NTx had rather high diagnostic validities among all markers examined in this study.     

Correlation of renal images on bone scan and intravenous pyelogram

In a controlled study in Ghana, the hemoglobin electrophoretic pattern in 112 patients with Burkitt's lymphoma was compared to that of their nearest neighbor controls of the same age, sex, and tribe, as well as their sibling controls. Analysis of the data obtained did not show any statistically significant protective advantage for sickle cell trait against Burkitt's lymphoma. Hemoglobin C trait appeared to offer a slight protective advantage (p less than 0.1), but this did not reach statistical significance. These results do not disprove the malaria co-factor hypothesis in the etiology of 0urkitt's lymphoma, but deprive it of an additional indirect evidence in its favor.     

Changes of bone metabolic markers in patients with bone metastases: clinical significance in assessing bone response to chemotherapy

To determine the changes in bone metabolism in response to combined chemotherapy in patients with bone metastases (BM), we examined osteocalcin (BGP), alkaline-phosphatase (ALP), hydroxyproline (HYP), pyridinoline (PYR), and/or deoxypyridinoline (D-PYR) in 25 cancer patients. In patients without BM, serum BGP was normal and not affected by chemotherapy. In patients with BM, however, BGP was often abnormally high or low, and some patients reacted to chemotherapy with a BGP increase at 4 weeks after initiation of therapy. Such an increase was observed in the group of patients who responded favorably to therapy as judged by a decrease in bone pain and tumor-associated biochemical markers. Urine HYP, PYR, and D-PYR were high in patients with BM before therapy; D-PYR decreased transiently at 2 weeks and increased thereafter. We assume that increased bone-resorption markers along with increased bone formation markers after therapy would indicate recovery of coupled bone metabolism, as the deranged bone remodeling is improved by tumor-regression. This study suggests that BGP and D-PYR can be useful early markers to predict favorable bone response to chemotherapy in patients with BM.     

Identification of metabolic bone disease in patients with endogenous hyperthyroidism: role of biological markers of bone turnover

Active hyperthyroidism is associated with reduced bone mass. Nevertheless, not all patients show the same risk for developing osteoporosis. Our aim was to analyze some clinical and biochemical potential predictors of low bone mass in hyperthyroid patients. We studied 127 consecutive hyperthyroid patients (110 females, 17 males; aged 42 +/- 16 years). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) at lumbar spine (LS; L2-L4) and femoral neck (FN). Data were expressed as g/cm2 and T-score. Patients were placed into two groups based on recent WHO criteria: Group A, no osteoporosis (n = 98); and group B, lumbar or femoral osteoporosis (n = 29). Study protocol included evaluation of osteoporosis risk factors, anthropometrical variables, thyroid function, and bone turnover markers. Receiver-operating characteristic (ROC) plots for the precision of bone markers and multivariate analysis for the prediction of BMD and osteoporosis were performed. Group B showed greater age and proportion of menopausal females; lower weight, height, and calcium intake; longer duration of menopause; and greater levels of total and bone alkaline phosphatase and of urine hydroxyproline. No differences in thyroid function, osteocalcin, tartrate-resistant acid phosphatase, and type I collagen C-telopeptide (ICTP) were found. The best predictive model accounted for 46% and 62% of the variability of lumbar and femoral BMD respectively and correctly classified 89% of the osteoporotic hyperthyroid patients. No significant difference in ROC plots was observed. It is concluded that hyperthyroid patients with lumbar or femoral osteoporosis show a typical clinical and biochemical profile illustrating that the relationship between BMD and bone markers is better in high turnover states. Classical bone turnover markers show high performance in the evaluation of hyperthyroid bone disease.     

The usefulness of early whole body bone scintigraphy in the detection of bone metastasis from prostatic cancer

Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of 99mTc-HMDP. The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformans were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, gamma-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases.     

骨转换标志物在非小细胞肺癌骨转移临床应用价值的研究

Objective:The purpose of this study was to assess the clinical application value of bone turnover markers in non-small-cell lung cancer (NSCLC) patients with bone metastases. Including diagnosing bone metastases, detecting bone metastatic spread. Methods: Alkaline phosphatase (AKP), p-C-terminal telopeptide of type I collagen (B-CTx), osteocalcin (OST) and bone alkaline phosphatase (BALP) were measured in 76 patients with bone metastases from NSCLC and 44 normal people. Results: The level of AKP, B-CTx and BALP in patients with bone metastasis was significantly higher than in the normal people. Significant correlation was observed among bone turnover markers. The levels of BALP and OST were significantly correlated with the extent of bone metastasis. The patients with high-level CTx and low-level BALP had higher risk of pathologic fracture. Conclusion: In NSCLC patients with bone metastases, bone turnover markers can help to make diagnosis and evaluate the severity. It will have a wide range of use in clinical practice.     

Correlation between extent of myocardial dysfunction and markers of irreversible damage in failing hearts

Using a SOM (self-organizing map) we can classify sequences within a protein family into subgroups that generally correspond to biological subcategories. These maps tend to show sequence similarity as proximity in the map. Combining maps generated at different levels of resolution, the structure of relations in protein families can be captured that could not otherwise be represented in a single map. The underlying representation of maps enables us to retrieve characteristic sequence patterns for individual subgroups of sequences. Such patterns tend to correspond to functionally important regions. We present a modified SOM algorithm that includes a convergence test that dynamically controls the learning parameters to adapt them to the learning set instead of being fixed and externally optimized by trial and error. Given the variability of protein family size and distribution, the addition of this features is necessary. The method is successfully tested with a number of families. The rab family of small GTPases is used to illustrate the performance of the method.     

Radiographic skeletal survey and radionuclide bone scan in Langerhans cell histiocytosis of bone

BACKGROUND: The lack of a consensus in the literature on the imaging strategy in Langerhans cell histiocytosis (LCH) bone lesions in childhood. OBJECTIVE: To evaluate the relative value of radionuclide bone scan (RBS) and radiographic skeletal survey (RSS) in the detection of LCH bone lesions, both in the initial work-up of the disease and during the follow-up period. MATERIALS AND METHODS: Ten children with bone lesions evaluated by means of RSS and RBS in a retrospective study (1984-1993). RESULTS: Fifty radiologically and/or scintigraphically abnormal foci were detected: 27 anomalies in the initial work-up (12 by both RSS and RBS, 8 by RSS only and 7 by RBS only) and 23 additional anomalies during follow-up (10 by both RSS and RBS, 10 by RSS only and 3 by RBS only). RSS+/RBS- lesions (n = 18) are more frequently encountered in the skull (P = 0.038), and more frequently lack radiologic signs of osteoblastic activity (P = 0.020), than RSS+/RBS+ lesions (n = 22). RSS-/ RBS+ abnormalities (n = 10) were most frequently insignificant. CONCLUSION: In the initial work-up both RSS and RBS should be carried out, while in the follow-up only RSS should be performed.     

Detection of skeletal metastases in Nigerian breast cancer patients: evaluation of radioisotope bone scan and radiography

Cerebellar granule cells isolated from postnatal day 7 mice, and cultured in minimal medium containing only insulin-like growth factor-I (IGF-I), both survive and differentiate. This differentiation is marked by neurite growth and expression of genes associated with terminal differentiation, the myocyte-specific enhancer factor 2A (MEF2A) and the alpha 6 subunit of the gamma-aminobutyric acidA receptor (GABAA alpha 6). Percoll gradient purified granule cells maintained without IGF-I, in minimal medium alone or in medium containing the antioxidant N-acetylcysteine (NAC), also express MEF2A and GABAA alpha 6. Thus, cultured granule neurons can differentiate to some extent cell-autonomously and IGF-I may not be a critical factor for this process.     

A comparison between lymphangiography and pelvic node dissection in the staging of prostatic cancer

On 40 consecutive patients with prostatic cancer who had pedal lymphangiography during the initial evaluation and, subsequently, underwent pelvic node dissection or biopsy, a surprisingly high number had falsely positive (59 per cent) or negative (36 per cent) x-ray findings. Initially the tumors were considered clinically to be stage B in 24 cases, stage C in 13 and stage D in 3. After lymph node dissection only 17 tumors were still considered to be stage B and 7 were stage C, while 16 tumors were actually stage D. This surgical staging is important for the further management of the patient as well as the prognosis, Pedal lymphangiogrpahy alone is unreliable for accurate assessment of the regional lymph node status in clinically localized prostatic cancer.     

Linkage between markers in the vicinity of the uncoupling protein 2 gene and resting metabolic rate in humans

The recent cloning of a gene that codes for a novel uncoupling protein, UCP2, which is expressed in a wide range of adult human tissues, has raised the possibility that it may be involved in regulation of energy balance. To explore this concept we have investigated potential linkage relationships between three microsatellite markers which encompass the UCP2 gene location on 11q13 with resting metabolic rate (RMR), body mass index, percentage body fat (%FAT) and fat mass (FM) in 640 individuals from 155 pedigrees from the Québec Family Study. Using a linkage analysis strategy based on sibling, avuncular, grandparental and cousin pairs, strong evidence of linkage was found between the marker D11S911 (P = 0.000002) and RMR, with more moderate evidence for D11S916 (P = 0.006) and D11S1321 (P = 0.02). Suggestive evidence of linkage was also observed between D11S1321 and %FAT (P = 0.04) and FM (P = 0.02). It is concluded that the three markers encompassing the UCP2 locus and spanning a 5 cM region on 11q13 are linked to resting energy expenditure in adult humans. The evidence is strong enough to warrant a search for DNA sequence variation in the gene itself.     

Genome scan for human obesity and linkage to markers in 20q13

Obesity is a highly prevalent, multigenic trait that predicts increased morbidity and mortality. Here we report results from a genome scan based on 354 markers in 513 members of 92 nuclear families ascertained through extreme obesity and normal body weight. The average marker interval was approximately 10 cM. We examined four correlated obesity phenotypes, including the body-mass index (BMI) (both as a quantitative trait and as a discrete trait with a threshold of BMI > or /=30 kg/m2) and percentage of fat (both as a quantitative trait and as a discrete trait with a threshold of 40%) as assessed by bioelectrical impedance. In the initial stage of the genome scan, four markers in 20q gave positive evidence for linkage, which was consistent across most obesity phenotypes and analytic methods. After saturating 20q with additional markers (25 markers total) in an augmented sample of 713 members from 124 families, we found linkage to several markers in a region, 20q13, previously implicated in both human and animal studies. Three markers (D20S107, D20S211, and D20S149) in 20q13 had empirical P values (based on Monte Carlo simulations, which controlled for multiple testing) < or /=. 01 for single-point analysis. In addition, the parametric, affecteds-only analysis for D20S476 yielded a LOD score of 3.06 (P=. 00009), and the affected-sib-pair test yielded a LOD score of 3.17 (P=.000067). Multipoint analyses further strengthened and localized these findings. This region includes several plausible candidate genes for obesity. Our results suggest that one or more genes affecting obesity are located in 20q13.     

Changes in bone mass and serum markers of bone metabolism after parathyroidectomy

BACKGROUND: Primary hyperparathyroidism (PHPT) is associated with an increased bone turnover. The simultaneous use of biochemical and bone mass measurements before and after parathyroidectomy is sparsely reported. This study was carried out to evaluate changes in bone mass and markers of bone metabolism in postmenopausal women with PHPT after parathyroidectomy. METHODS: Twelve women, mean age of 63 years, were investigated. Measurements of bone mineral density (total body, spine, hip, and forearm bone mineral density) with dual-energy x-ray absorptiometry were performed before operation and at follow-up at a median of 23 months. Concomitantly, changes in serum intact parathyroid hormone, bone-specific alkaline phosphatase (B-ALP), osteocalcin, carboxyterminal propeptide of type I procollagen, and the immunoactive carboxyterminal telopeptide of type I collagen were recorded. RESULTS: At follow-up a significant increase in bone mineral density of the spine (p < 0.05), femoral neck (p < 0.05), Ward's triangle (p < 0.05), and trochanter (p < 0.01) was observed. No significant changes in the forearm were registered. Levels of parathyroid hormone, B-ALP, and osteocalcin were elevated and intercorrelated before operation. The serum levels of these parameters decreased significantly after operation. Serum levels of carboxyterminal propeptide of type I procollagen and the immunoactive carboxyterminal telopeptide of type I collagen did not significantly differ from a reference population, and no major changes were observed at follow-up. CONCLUSIONS: Bone mineral density in the spine and hip is improved after parathyroidectomy in postmenopausal women with primary hyperparathyrodism. Serum levels of B-ALP and osteocalcin are elevated in PHPT and decrease after operation. The clinical usefulness of serum markers of collagen metabolism in investigating bone metabolism in PHPT seems limited.