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)

A series of 30 patients is reported whose primary hepatic tumors had a distinctive histologic pattern that we have called "sclerosing hepatic carcinoma" (SHC). Sixty-nine percent of those tested had hypercalcemia and low levels of serum phosphate. As comparison, 38 control patients who had either classical peripheral cholangiocarcinoma or typical hepatocellular carcinoma were studied. In the control group, only two patients, who also had bone metastases, had hypercalcemia. Sclerosing hepatic carcinoma is characterized by intense fibrosis in which the tubular neoplastic structures are embedded. Although the tumor in each patient superficially resembled peripheral cholangiocarcinoma, on close inspection 63% were found to be of apparent hepatocyte origin, 20% were apparently ductal, and 13% were mixed or not distinguishable. One patient's tumor had the pattern of the rare cholangiolocellular carcinoma. The difficulty of histological diagnosis was well illustrated by the fact that none of premortem biopsies in 16 patients was correctly interpreted unequivocally as primary carcinoma of the liver. Many were misinterpreted as metastatic adenocarcinomas, most frequently of pancreatic origin. We believe that, by describing clinicopathological features, more attention will be drawn to this unique carcinoma of liver origin.
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PMID:Sclerosing hepatic carcinoma: relationship to hypercalcemia. 629 35

The diphosphonates are a group of phosphate compounds which inhibit the growth and dissolution of apatite crystals. These drugs have similar biological effects on bone by inhibiting the osteoclasts, and are also active in preventing pathological calcifications. The diphosphonates have been used successfully in various bone diseases and are now currently used for bone scanning. They are also considered one of the best treatments for Paget's disease. Several experiments in vitro and in vivo have suggested that the diphosphonates are active against bone metastases. Clinical trials have been undertaken and have shown that these compounds are active against malignant hypercalcemia. Further, they may delay the extension of bone destruction due to malignancy.
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PMID:[Diphosphonates in the treatment of bone metastases]. 646 Mar 13

Calcitonin obtained from eels (ell-CT) was given to 14 patients who had developed bony pains due to bone metastases of malignant tumors and who did not respond to 12 various analgesics. The patients consisted of 12 males and 2 females, with a mean age of sixty-five. Eel-CT (Elcitonin) was injected intramuscularly to each patient at a dose of 40 units twice daily. Other analgesics were assessed to be ineffective at the time of CT administration and they were not given consideration in the evaluation. For the assessment of drug effect, a pain score was prepared. Eel-CT was markedly effective in 3 patients, effective in 8 patients, and ineffective in 2 patients. Eel-CT had a better effect on prostatic cancer than any other cancer. The analgesic effect was observed in the first week of drug administration at around a total dose of 1,000 units. Although the pain tended to appear at regions on which the body weight was liable to rest, the analgesic effect was seen irrespective of the side of pain. Since serum calcium, phosphate, parathyroid hormone (PTH), CT levels and bone scintigrams between pre-and post-CT administration did not differ, the analgesic mode of action of CT is not supposed to be related to inhibition of bone absorption nor bone formation. The therapeutic effect hardly suggests any direct action of CT on the tumor.
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PMID:[Effect of calcitonin on body pains caused by bone metastases of urogenital cancer]. 667 46

An 89-year-old man with bilateral leg edema and a huge abdominal mass was admitted for further evaluation. CT scan showed a hugh prostatic mass which occupied the whole pelvis cavity accompanying multiple pelvic bone metastases. Suprapubic needle biopsy revealed that the mass was well differentiated adenocarcinoma of prostate origin. The treatment was initiated by 500 mg per day of estramustine phosphate combined with injectable LH-RH analogue 2 months later. The serum levels of tumor markers were markedly elevated at the first visit; PSA 210ng/ml, PAP 110ng/ml, gamma-Sm 800ng/ml. They became normalized 3 months after the initiation of the treatment, and the mass was reduced to 11.5% of the initial size, which lead to removal of indwelling urethral catheter. The patient and his family, however, refused further treatment and the patient died of disseminated disease 8 months later.
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PMID:[A case of huge prostate cancer]. 748 33

A rare case of gastric carcinoma associated with increased serum variant alkaline phosphatase activities is presented. A 54 year old man had extremely high serum alkaline phosphatase activity (18,607 U/l) with normal calcium and phosphate concentrations. His bone scintigram showed abnormal findings, 'super bone scan'. He was diagnosed as having Borrmann type 4 gastric carcinoma with diffuse bone metastases by examinations of the upper gastrointestinal tract and iliac bone biopsy. The alkaline phosphatase isozyme of this patient was of the bone type as measured by cellulose acetate membrane electrophoresis and the placenta/bone type by agarose gel electrophoresis, respectively. Immunoelectrophoresis and the immunoprecipitation method using monoclonal antibodies against various alkaline phosphatase isozymes, however, showed that his serum alkaline phosphatase had the liver type antigenicity. Furthermore, it had a larger molecular size and different sugar chains compared with the common liver type alkaline phosphatase. These findings suggest that a unique variant alkaline phosphatase was produced by gastric cancer cells, which is possibly an explanation for the high serum alkaline phosphatase activities in this patient.
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PMID:A variant alkaline phosphatase found in a case of gastric carcinoma with super bone scan. 788 33

57 patients with advanced prostate cancer and a failure of prior hormonal treatment were selected for a double-blind placebo-controlled trial, in which they were randomly allocated to receive either clodronate (C) or placebo concomitantly with the basic cancer treatment, estramustine phosphate (E) (560 mg daily). The treatment was started intravenously with 300 mg of C or placebo in 5 consecutive days, and thereafter maintained orally with 1600 mg of C or identical placebo daily for 3 months. Bone biopsies were taken at admission and at 3 months. Measurements of serum calcium, phosphate, alkaline phosphatase, prostate-specific antigen and creatinine were made at the time of both bone biopsies and at 1 month. Serum intact parathyroid hormone and vitamin D metabolites were measured at admission and at 3 months. Because of several discontinuations, the study groups at final analysis comprised 20 patients taking E + C and 19 patients taking E and placebo. Bone resorption, as judged by eroded surface and osteoclast number, was markedly increased especially in biopsies taken from tumour-involved bone. Treatments with E + C or E both induced a significant decrease in bone resorption, but were associated with the development of hypocalcaemia, secondary hypoparathyroidism, hypophosphataemia and severe impairment of mineralisation of newly formed bone, i.e. osteomalacia. Since the patients were not vitamin D deficient, we conclude that osteomalacia resulted from a relative deficiency of calcium and phosphate. The transiency of pain relief achieved with anti-resorptive agents in the treatment of bone metastases from prostate cancer may be due to the development of osteomalacia.
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PMID:The effect of clodronate on bone in metastatic prostate cancer. Histomorphometric report of a double-blind randomised placebo-controlled study. 791 32

To find out if the concentration of parathyroid hormone-related protein (PTHrP) predicts the response of tumour-inducing hypercalcaemia (TIH) to pamidronate, we studied 44 patients. Pretreatment measurements of serum PTHrP, calcium and phosphate, nephrogenous cyclic AMP, tubular threshold for calcium and phosphate (TmP), and the presence of bone metastases were correlated with response to pamidronate. Response was considered good (normal calcium concentration corrected for albumin [CCa] for > 14 days), or poor (failure of CCa to fall, or a rise above normal < or = 14 days). PTHrP correlated significantly with response (good vs poor, p = 0.02). Undetectable PTHrP (< 2 pmol/L) was associated with a good response in all seven treatments, PTHrP in the range 2-12 pmol/L was associated with good response in 10 of 14 treatments, while PTHrP > or = 12 pmol/L was associated with a poor response in all 11 treatments. Tubular threshold for calcium correlated with the fall in CCa by day 6 after treatment (p = 0.02). Urinary clearance estimations in poor responders suggested that there was an incomplete reversal of the renal tubular component of hypercalcaemia. Serum PTHrP correlates with response to pamidronate in the treatment of TIH; which may be associated with a renal tubular mechanism not significantly affected by currently available treatment. Drugs that inhibit tubular reabsorption of calcium or PTHrP secretion may help in patients who do not respond to pamidronate.
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PMID:Parathyroid hormone-related protein and response to pamidronate in tumour-induced hypercalcaemia. 810 20

Hypercalcemia is relatively frequent in malignancy with or without osteolytic bone metastases. It is thought that neoplastic cells may secrete substances which not only stimulate osteoclastic activity but are also capable of modifying the absorption, excretion, and resorption of calcium and phosphate ions. Since 1987, we have studied 24 breast cancer patients with hypercalcemia (22 with bone metastases and two without). The group of 22 patients with bone metastases were divided into two subgroups. The first consisted of 10 patients with high serum levels of humoral factors, such as parathyroid hormone-related protein (PTHrP), and/or prostaglandin E2 (PGE2) and/or interleukin 1 (IL-1), and high levels of bone markers, such as alkaline phosphatase, bone Gla protein and urinary hydroxyproline. The second subgroup consisted of 12 patients with high levels of bone markers alone. Bone histologic analysis showed an osteoclastic activation surrounding metastatic tumor tissue in six out of 10 patients of the first subgroup, while an evident osteolysis caused by the tumor cells was noted in seven out of 12 patients of the second subgroup. The two patients without bone metastases showed normal biochemistry and bone histologic examination. The authors, having tried to explain the pathogenesis of hypercalcemia, emphasize the importance of humoral factors secreted by tumor cells as a direct or indirect cause of hypercalcemia. The origin of hypercalcemia remains unclear in two patients without bone metastases.
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PMID:Hypercalcemia in breast cancer. 837 11

Estramustine phosphate is generally used as a second-line treatment in patients with advanced prostate cancer. The bone metastases due to the cancer are often treated simultaneously with clodronate in order to relieve the bone pain. Therefore, the interaction of clodronate (800 mg orally four times daily) and estramustine phosphate (280 mg orally twice daily) on their bioavailability was studied in twelve patients with prostate carcinoma and bone metastases. The drugs were first given separately, each to six patients, for five days, and then concomitantly for the same period. The bioavailabilities of the drugs were calculated on the last day of each treatment period. When clodronate was given alone, its concentrations in serum and AUC for one dose interval (6 hr) did not differ from those obtained with the drug given concomitantly with estramustine phosphate, nor did the combination of estramustine phosphate change the excretion of clodronate in urine. The serum concentrations of estramustine phosphate were elevated by about 80% when the drug was given together with clodronate. The AUC for one dose interval (12 hr) was also significantly higher for estramustine phosphate with clodronate than without clodronate. The urinary excretion of estrone, a major metabolite of estramustine phosphate, was also significantly higher after the admission with clodronate. The results suggest that clodronate increases the oral bioavailability of estramustine phosphate.
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PMID:Effect of concomitant administration of clodronate and estramustine phosphate on their bioavailability in patients with metastasized prostate cancer. 888 75

The purpose of this investigation was to characterise the in vivo chemistry and binding mechanisms of technetium-99m dimercaptosuccinic acid [99mTc(V)DMSA]. Biodistribution was studied in mice by frozen section whole-body autoradiography and microautoradiography in selected tissues. Binding to bone mineral analogues was studied in vitro using various forms of calcium phosphate and hydroxyapatite under varied conditions. Similar studies with 99mTc-hydroxymethylene diphosphonate (HDP) were also carried out for comparison. The in vivo stability of 99mTc(V)DMSA was monitored by high-performance liquid chromatographic analysis of blood and urine samples taken over 24 h from patients injected with the tracer. Whole-body autoradiography shows that 99mTc(V)DMSA has highest affinity for bone (cortical rather than medullary) in mice. Substantial uptake of the tracer was also observed in the kidney (cytoplasm of cortical renal tubular cells). No specific localisation was observed in the liver at either the microscopic or the macroscopic level. While 99mTc-HDP bound strongly to calcium phosphates under all conditions, 99mTc(V)DMSA binding was inhibited in the presence of phosphate and was stronger at pH 6.0 than at pH 7. 4. In non-phosphate buffers, however, the binding of 99mTc(V)DMSA remained high across the pH range 4-7.4. 99mTc(V)DMSA binds to calcium phosphates chemically unaltered, and no radioactive species other than the three isomers of 99mTc(V)DMSA were detected in blood or urine samples taken from patients up to 24 h after injection. 99mTc(V)DMSA is stable in vivo, and no conversion of the complex to other chemical species needs to be invoked to explain its uptake in bone metastases or soft tissue tumour. Bone affinity may be due to reversible binding of the unaltered complex to the mineral phase of bone.
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PMID:In vitro and in vivo studies with pentavalent technetium-99m dimercaptosuccinic acid. 892 10


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