Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case of a 36 year old patient in whom breast cancer was diagnosed in February 1983 is reported. At the time of the diagnosis bone metastases, were already present. Therapy was started on the basis of a FAC-regimen (Ftorofur-, Adriamycin-Cyclophosphamide), where after the patient developed clinical and laboratory signs of hepatic lesion. At the time of the first FAC-course the suspicion of viral hepatitis of cholestatic type was raised; HBsAg was consistently negative. In the 3rd week after completion of the second FAC-course clinical signs of cholestatic hepatitis with high fever and leucopenia of increasing severity were suggestive of drug-induced hepatitis. Cyclophosphamide was incriminated, therefore, this component was omitted from the subsequent FAC-course. Nevertheless, the clinical manifestations reappeared in a more pronounced form. This time, too steroids were administered, with beneficial effect. In view of the complaints pointed to bone-metastases further cytostatic treatment, Vepesid monotherapy was started, but after the first course the patient developed hepatitis and died. Necropsy revealed, in addition to extensive bone-metastases, microscopic signs of drug-induced hepatitis. The types of liver damage caused by the cytostatic agents used in this study are reviewed. No hepatitis has been reported in connection with these drugs (Adriamycin + Ftorofur or Vepesid) thus far. The diagnostic criteria of drug-induced hepatitis are outlined. It is pointed out that with the eves more extensive use of cytostatic therapy a growing incidence of this complication should be taken into account.
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PMID:Drug hepatitis of cholestatic type in association with a FAC-regimen for breast cancer. 344 15

60 patients with metastatic breast cancer were entered in a phase II study using folinic acid, 5-fluorouracil bolus and infusion and mitoxantrone with or without cyclophosphamide. 47 had measurable visceral metastases and 13 had exclusively bone metastases. 36 had received previous adjuvant or metastatic treatment (33/36 with anthracycline-based regimens). Overall response rate in visceral metastatic patients was 57.1% [95% confidence interval (CI) 35.4-78.8%]; 45.5% and 70% in previously and non-previously treated patients, respectively; duration of response was 9 and 13 months, respectively. 10 out 13 patients with exclusive bone metastases improved for a median time of 18 months. Median survival was 22 months for the 60 patients; 18 and 31 months for previously and non-previously treated patients, respectively. Cyclophosphamide was scheduled only in the absence of nadir grade 4 neutropenia. However, this toxicity occurred in the first 7 patients. For this reason, we chose to avoid cyclophosphamide in patients over 60 years, or with a performance status of 1-2, or who had received previous chemotherapy. Overall, cyclophosphamide was stopped due to nadir grade 4 neutropenia in 17/24 patients for whom this drug was planned. When mitoxantrone, 5-fluorouracil and folinic acid were used at the doses scheduled, the addition of cyclophosphamide appeared feasible in only about 25% of the patients. Furthermore, survival was identical for patients receiving or not receiving cyclophosphamide. Therefore, cyclophosphamide does not contribute substantially to this regimen. This study confirms the value of folinic acid, 5-fluorouracil and mitoxantrone in metastatic breast cancer.
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PMID:Folinic acid, 5-fluorouracil bolus and infusion and mitoxantrone with or without cyclophosphamide in metastatic breast cancer. 826 Feb 36

Breast cancers frequently have osteoclastic bone metastases that are difficult to monitor and treat. Bone scintigraphy with 99mTc-labeled biphosphonates is still the reference method for detecting and localizing bone involvement. Classical biochemical markers such as urinary calcium have poor sensitivity for detecting and monitoring metastases of breast cancers. New biochemical markers for the study of bone remodeling have recently been developed, including a degradation product of the C-terminal end of the telopeptide of type I collagen (CTX). We used an immunoenzymatic assay technique for urinary CTX in 84 pre- and post-menopausal women and demonstrated a correlation between scintigraphic scores and urinary CTX concentrations. CTX values are significantly different between the control group and patients with bone metastasis, except those with score 0. There is a regular increase in urinary CTX concentration from score 0 (no abnormal uptake) to score 4 (diffuse carcinomatosis). There is no significant variation between control population and score 0 to 3 for urinary calcium. Only women with scintigraphic score 4 have significantly increased urinary calcium concentrations. Measuring CTX in pre- and post-menopausal patients during breast cancer chemotherapy might be of great interest for monitoring the development of metastases and the therapeutic efficacy of chemotherapy.
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PMID:Urinary carboxyterminal telopeptide of collagen I as a potential marker of bone metastases chemotherapy monitoring in breast cancer. 1021 29

Although urinary measurements of collagen degradation provide valid estimates of bone resorption, their clinical application is hampered by pronounced analytical and biological variability. Therefore, immunoassays for the determination of such parameters in serum have been developed. In this study, we assessed the performance of three new serum markers of bone turnover, i.e., C-terminal and N-terminal telopeptides of type I collagen (S-CTX and S-NTX) and bone sialoprotein. Results were compared with urinary total pyridinoline, total deoxypyridinoline, and urinary C-terminal telopeptides of type I collagen (U-CTX) and urinary N-terminal telopeptides of type I collagen (U-NTX). The study population included healthy men (n = 27), premenopausal (n = 30) and postmenopausal (n = 31) women, patients with hepatic dysfunction (HF, n = 24), renal failure (RF, n = 30), breast cancer without (BC-, n = 24) and with (BC+, n = 30) bone metastases, primary vertebral osteoporosis (OPO, n = 27), primary hyperparathyroidism (PHPT, n = 16), active Paget's disease of bone (n = 18), multiple myeloma (MM, n = 18), and patients with hypercalcemia of malignancy before and after treatment with pamidronate (HOM, n = 28). Changes in urinary and serum markers were similar in most metabolic bone diseases. However, differentiation between healthy controls and OPO, or PHPT, was improved by the serum markers. In MM, all serum and urinary markers were elevated (p < 0. 05 vs. controls). In BC+, skeletal involvement was reflected by significant increments in all indices (p < 0.01 vs. BC-), except U-CTX and S-CTX. In HOM, pamidronate-induced changes in biomarkers were most pronounced for U-CTX and S-CTX and S-NTX. HF and RF were associated with elevated levels of all serum markers (p < 0.05 vs. controls). In conclusion, measurements in serum reflect bone resorption to the same extent as the urinary indices. Since serum markers circumvent some of the limitations of urinary measurements, their use potentially improves the assessment of skeletal disorders.
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PMID:Novel serum markers of bone resorption: clinical assessment and comparison with established urinary indices. 1032 May 28

Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to that of bone formation in patients with bone metastases from prostate cancer before and after bisphosphonate treatment. Thirty-nine patients with prostate cancer and bone metastasis, nine patients with prostate cancer without bone metastases, nine patients with benign prostatic hyperplasia and 355 healthy age-matched men were included. Urinary non-isomerized (alpha CTX) and beta isomerized (beta CTX) type I collagen C-telopeptides (CTX) and a new assay for serum CTX were used to assess bone resorption. Bone formation was determined by serum osteocalcin, serum total (T-ALP) and bone (BAP) alkaline phosphatase and serum type I collagen C-terminal propeptide (PICP). Fourteen patients with bone metastases were also evaluated 15 days after a single injection of the bisphosphonate pamidronate (120 mg). Levels of all bone formation and bone resorption markers were significantly (P < 0.006-0.0001) higher in patients with prostate cancer and bone metastasis than in patients with benign prostatic hyperplasia, patients with prostate cancer without bone metastases and healthy controls. In patients with bone metastases the median was increased by 67% for serum osteocalcin, 128% for T-ALP, 138% for BAP, 79% for PICP, 220% for urinary alpha CTX, 149% for urinary beta CTX and 214% for serum CTX. After bisphosphonate treatment all three resorption markers significantly decreased by an average of 65% (P = 0.001), 71% (P = 0.0010) and 61% (P = 0.0015) for urinary alpha CTX, urinary beta CTX and serum CTX, respectively, whereas no significant change was observed for any bone formation markers. Patients with prostate cancer and bone metastases exhibit a marked increase in bone resorption, which decreases within a few days of treatment with pamidronate. These findings suggest that these new resorption markers may be useful for the management of these patients.
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PMID:Markers of bone turnover for the management of patients with bone metastases from prostate cancer. 1073 59

A 66-year-old female presented with a swollen lump in the left breast. She was diagnosed as having advanced breast cancer of stage T4N3 (supraclavicular lymph node) M1 (bone). The administration of CEF and TAM failed to improve her condition. After the treatment regimen was changed to combined chemoendocrine therapy with CPA, EPI, 5'-DFUR, and MPA, the areas of bone metastases were reduced. However, MPA caused side-effects (acute obstruction of the lower limb), and thus the treatment was discontinued after 4 months. Subsequently, the treatment combination was changed to CPA, EPI, 5'-DFUR, and fadrozole hydrochloride hydrate. After one year of the treatment, a complete response (CR) was obtained with the disappearance of the supraclavicular lymph node and bone metastases. After EPI reached the maximum administration amount, the remaining CPA, 5'-DFUR and fadrozole hydrochloride hydrate oral administrations were continued. As of 3 years and 10 months after the onset of the chemoendocrine therapy, CR has been maintained with suppression of the primary and metastatic lesions, without degrading the patient's quality of life.
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PMID:[Efficacy of combined chemoendocrine therapy with doxifluridine, cyclophosphamide, and fadrozole hydrochloride hydrate in a case of stage T4N3M1 breast cancer]. 1083 48

In the collagen type I C-telopeptide an aspartyl-glycine site within the sequence AHDGGR is susceptible to molecular rearrangement. In newly synthesized collagen this site is in the native form, denoted alpha L. During aging a spontaneous reaction occurs resulting in three age-modified forms: an isomerized form (beta L) a racemized form (alpha D), and an isomerized/racemized form (beta D). In this study, we measured the urinary excretion of the four forms of C-telopeptides (CTX) in healthy adults and in patients with bone diseases. Levels of all CTX forms were higher in healthy postmenopausal women (P<0.001) compared with premenopausal controls. Levels decreased within 3 days of bisphosphonate treatment indicating that all CTX forms reflect bone resorption. In hyperthyroidism, characterized by a generalized increased bone turnover, native (alpha L) and age-modified (beta L, alpha D and beta D) forms increased to a similar extent compared to controls, resulting in normal ratios between the alpha L and age-modified forms of CTX. Conversely, in Paget's disease and prostate cancer-induced bone metastases, conditions characterized by focal increased bone turnover, alpha L CTX levels were more elevated than those of age-related CTX forms, resulting in increased ratios between native and age-modified CTX. For example, the ratio alpha L/alpha D was increased 7-fold in Paget's disease (P<0.001) and 2-fold in prostate cancer-induced bone metastases (P<0.002). In conclusion, the study suggests that in conditions with a localized alteration in bone turnover the ratio between alpha L CTX and the age-modified forms is significantly elevated. This may provide a new diagnostic and monitoring tool for diseases such as metastatic bone cancer and Paget's disease.
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PMID:Investigation of bone disease using isomerized and racemized fragments of type I collagen. 1238 13

Variability of bone marker measurements is a major problem in their clinical application. Most studies on marker variability have been performed in healthy subjects and over relatively short intervals of time. We prospectively evaluated the long-term variability of bone markers in 102 postmenopausal women diagnosed with primary breast cancer. During follow up (8-48, median 30 mo.), no patient developed bone metastases or other skeletal disease. Patients were seen every 3 months and exactly timed blood/urine specimens were obtained. All analyses were performed after study end by the same technician, using a single batch of reagents per analyte. The coefficient of variation was calculated as CV (%) = square root(sigma(CVi2)/n) (CVi = SD/mean x 100; n = n of CVi). The least significant change (LSC) was then LSC (%) = Z x CV x square root(2). Z = 1.96 for a 95% confidence interval (LSC-95). In a subset of n = 10 patients with no potential interference during follow-up, lowest CVs were recorded for serum (s) calcium (5%), sTAP (12%) and sBAP (14%). The LSC-95 for these markers were 14%, 33% and 39%, respectively. Highest CVs were seen with urine (56%) and serum (42%) CTX (LSC-95: 155%, 117% resp.). We conclude that in breast cancer patients without bone metastases, long-term variability varied greatly between markers. For certain markers, the LSC seems considerably higher than previously reported.
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PMID:Long-term variability of bone turnover markers in patients with non-metastatic breast cancer. 1246 40

Degradation products of collagen type I can be measured by CrossLaps (CTX) immunoassays, providing an index of bone resorption. The CTX epitope EKAHDGGR comprises a DG-motif susceptible to post-translational modifications. In newly synthesized collagen this motif is in the native form denoted alphaCTX, but converts to an isomerized form (betaCTX) during aging of bone. Furthermore, the lysine residue (K) within the CTX epitope participates in inter-molecular cross-links in mature bone. The present paper describes an assay, ALPHA CTX ELISA for measurement of cross-linked alphaCTX molecules (alpha-alphaCTX) in urine. The ALPHA CTX ELISA demonstrated a high specificity and technical precision for measuring such fragments. The assay was evaluated in a cross-sectional study, comparing the urinary excretion of the marker in 100 breast cancer patients with bone metastases (BC+) and 15 breast cancer patients without metastases to bone (BC-) as well as 31 age-matched healthy post-menopausal women (PM). For comparison alpha, beta, and beta-betaCTX was also measured using commercially available immunoassays. In BC+ urinary alpha-alphaCTX increased significantly compared to BC- and PM with p-values of 0.005 and <0.0001, respectively. In contrast, the age-modified form beta-betaCTX, representing the degradation of old bone, was less increased. Z-score analysis was used to compare the ability of the CTX markers to discriminate between BC+ and PM. The alpha-alphaCTX marker was found to provide a far better discrimination (Z=7.5) than beta-betaCTX (Z=3.6). In conclusion, measurement of alpha-alphaCTX fragments may provide a clinically relevant assessment of bone resorption related to bone metastases.
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PMID:An immunoassay for measuring fragments of newly synthesized collagen type I produced during metastatic invasion of bone. 1520 36

Our aim was to assess the diagnostic accuracy of bone markers in serum of patients with prostate cancer (PCa) for early detection of bone metastases and their usefulness as predictors of PCa-caused mortality. In sera of 117 PCa patients (pN0M0, n = 39; pN1M0, n = 34; M1, n = 44), 35 healthy men and 35 patients with benign prostatic hyperplasia, bone formation markers [total and bone-specific alkaline phosphatase (tALP, bALP), amino-terminal procollagen propeptides of type I collagen (P1NP), osteocalcin (OC)], bone resorption markers [bone sialoprotein (BSP), cross-linked C-terminal (CTX) and cross-linked N-terminal (NTX) telopeptides of type I collagen, tartrate-resistant acid phosphatase isoenzyme 5b (TRAP)] and osteoclastogenesis markers [osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand (RANKL)] were measured. tALP, bALP, BSP, P1NP, TRAP, NTX and OPG were significantly increased in PCa patients with bone metastases compared to patients without metastases. OPG showed the best discriminatory power to differentiate between these patients. Logistic regression analysis resulted in a model with OPG and TRAP as variables that predicted bone metastasis with an overall correct classification of 93%. Patients with concentrations of OPG, P1NP, tALP, bALP, BSP, NTX, TRAP and CTX above cut-off levels showed significantly shorter survival than patients with low marker concentrations. Multivariate Cox proportional hazards regression revealed that only OPG and BSP were independent prognostic factors for PCa-related death. Thus, the importance of serum OPG in detecting bone metastatic spread, alone or in combination with other bone markers, and predicting survival in PCa patients has been clearly demonstrated.
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PMID:Comparison of 10 serum bone turnover markers in prostate carcinoma patients with bone metastatic spread: diagnostic and prognostic implications. 1525 51


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