Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin synthetase inhibitors have, in the past, been shown to inhibit osteolysis caused by breast carcinoma tissue in vitro. We therefore assessed the effect of Indomethacin and aspirin on some parameters of calcium metabolism in patients with breast cancer. Neither drug reduced the serum calcium in pateints with hypercalcemia, nor reduced skeletal destruction as measured by the urinary hydroxy proline: creatinine ratio and urinary calcium in normocalcemic or hypercalcemic patients with osteolytic metastases. A possible reason for the discrepancy between results obtained in vitro and in vivo is that there are two phases of bone destruction in breast cancer; the early phase dependent and the late phase independent of prostaglandin synthesis.
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PMID:Failure of indomethacin to reduce hypercalcemia in patients with breast cancer. 100 35

The urinary excretion of hydroxyproline, measured as the hydroxyproline: creatinine ratio, was useful in monitoring the progression of metastatic cancer of the breast. After new treatment was started changes in the hydroxyproline excretion occurred earlier than other clinically observable responses. The test could therefore be used for predicting the response to treatment and early detection of the sensitivity of the tumour to hormone therapy.
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PMID:Hydroxyproline excretion in patients with breast cancer and response to treatment. 112 25

Twenty postmenopausal women (aged between 46 and 67 years old) with skeletal metastases from breast carcinoma were treated with clodronate 450 mg i.v. daily for 5 days and thereafter with 100 mg i.m. daily for 10 days. All patients received standard hormonal therapy (tamoxifen). Symptomatic pain (evaluated according to a linear analog scale), performance status (according to Karnofsky), serum alkaline phosphatase, serum creatinine and osteocalcin were measured before and after treatment on days 5, 15, 30 and 45. Scanning by radiology were performed pre- and post-therapy. Bone pain was significantly reduced in 15 out of 20 patients. After clodronate treatment the base line value of circulating osteocalcin (3.2 +/- 1.6 ng/ml) showed a significant increase on days 30 and 45 (p less than 0.001). Radiological assessment of bone lesions showed stable disease in 18 patients and progression in two patients. No adverse side effects were observed. These data show that clodronate provided pain relief in 75% of treated patients and the increase in circulating osteocalcin levels can be considered a marker of the stabilization of skeletal metastatic lesions.
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PMID:Subjective and metabolic effects of clodronate in patients with advanced breast cancer and symptomatic bone metastases. 138 63

In a series of 51 patients with prostate cancer and obstructive uropathy, unilateral or bilateral obstruction was identified in 22 (43%) and 29 (57%) respectively. This included a non-functioning kidney in 12 patients. In 86% of patients the T category was advanced. Bone metastases were present in 36 cases (71%); 19 patients (37%) had chronic retention. All patients with metastatic disease underwent hormonal manipulation and 43 underwent transurethral resection of the prostate. External beam radiotherapy, percutaneous nephrostomy and ureteric reimplantation were performed in 4, 5 and 1 patient respectively. Actuarial survival of all 51 patients was 57 and 25% at 2 and 5 years. Presentation with bilateral or non-function did not predict a worse prognosis in comparison with patients with unilateral hydroureteronephrosis. Raised alkaline phosphatase and prostatic acid phosphatase were of no prognostic value, while creatinine reached marginal significance. A positive bone scan and raised urea were strongly predictive of a poor outlook. It was concluded that prostate cancer and obstructive uropathy should not uniformly imply a terminal event, and interventional therapy is justified with a 25% 5-year survival rate.
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PMID:Outcome and prognostic factors in patients with advanced prostate cancer and obstructive uropathy. 145 Aug 51

Chemotherapy is the only effective method of treating unresectable hepatoblastoma. Most protocols require the administration of multiple highly toxic agents. We evaluated the ability of single-agent high-dose cis-platinum (HD-CDDP) to shrink unresectable primary hepatoblastoma to allow resection. Seven children aged 11 to 72 months had unresectable hepatoblastoma based on size and location. Initial alpha-fetoprotein (AFP) levels were between 4,900 and 1,840,000 ng/mL (mean, 555,900 ng/mL). Chest computed tomography (CT) scans obtained before beginning HD-CDDP therapy showed multiple or bilateral lung masses in 3 patients. Chemotherapy for each of the 7 children consisted of only HD-CDDP, 150 mg/m2, at 3-week intervals. HD-CDDP was stopped and prompt resection performed when AFP levels ceased to decline significantly (n = 4; mean nadir, 18,600); the corrected creatinine clearance decreased below 60 mL/min (n = 2); or, in one case, significant hemorrhage occurred within the tumor. Therefore, the number of HD-CDDP doses given preoperatively varied between 1 and 7 (mean, 3). No children required dialysis. Tumor cells in the bone marrow of one child disappeared completely after one dose of HD-CDDP. Follow-up CT scans showed complete resolution of the pulmonary metastases in 2 children, a partial response in the third, and a marked reduction of primary tumors to resectable sizes. Six children underwent tumor excision with adequate margins; parents of the seventh child refused permission for surgery. There were 2 operative deaths, 3 deaths due to local or distant disease, and 2 patients survived (postoperative follow-up, 22 and 14 months).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Marked response to preoperative high-dose cis-platinum in children with unresectable hepatoblastoma. 165 88

In a controlled trial the effects of the osteoclast inhibitor disodium pamidronate were studied over a 6-month period in men with metastatic bone disease from prostate cancer. Using serial biochemical measurement of metabolic bone activity, and complementary subjective and quantitative bone histology, the effects of pamidronate were evaluated in tumour-free and metastatic regions of the skeleton, enabling analysis of the differential mechanisms of bone destruction in this disease. Following treatment, abnormally high markers of bone breakdown fell significantly (fasting urine hydroxyproline/creatinine (OHP): P less than 0.05; fasting urine calcium excretion (CaE): P less than 0.0001), confirming that activated osteoclasts play an integral role in the osteolytic process. Serial histomorphometry of bone from tumour-free areas showed that pamidronate restored abnormal levels of bone erosion to normal in 93% of cases. Suppression of bone destruction was also evident within metastases, although this was incomplete. The results confirm that osteoclast overactivity is responsible for a significant proportion of the accelerated osteolysis seen in both tumour-free and infiltrated bone in patients with prostate cancer. The differential effects in tumour-free and infiltrated bone suggest that the mechanisms of osteoclast activation may differ in metastatic and non-metastatic regions of the skeleton.
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PMID:Disodium pamidronate identifies differential osteoclastic bone resorption in metastatic prostate cancer. 173 55

Fasting venous blood collected from 83 patients with breast cancer was analyzed for triglycerides; total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol; tumor necrosis factor (TNF alpha); glucose; creatinine; insulin; glucagon; growth hormone; cortisol; and thyrotropin. Patients with stage IV disease had significantly higher (P less than 0.05) triglyceride concentrations and significantly lower (P less than 0.05) concentrations of total and HDL cholesterol than did patients with less advanced disease or age-matched controls. Furthermore, LDL cholesterol concentrations in patients with boney metastases were significantly lower (P less than 0.05) than concentrations in patients with liver or liver plus boney metastases or in controls. These results could not be attributed to smoking habits, alcohol consumption, or treatment. We observed no correlations between serum concentrations of lipid and concentrations of TNF alpha, insulin, glucose, creatinine, cortisol, growth hormone, or thyrotropin. However, there was a significant (P less than 0.05) negative correlation between total cholesterol and glucagon and between LDL cholesterol and glucagon for patients with stage II, III, and IV disease, suggesting that glucagon may reduce LDL cholesterol concentrations by an as-yet-unidentified mechanism.
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PMID:Alterations of serum lipids in breast cancer: effects of disease activity, treatment, and hormonal factors. 176 85

Seventy-seven patients with advanced urothelial cancer were treated with methotrexate, vinblastine, adriamycin, and cisplatin (M-VAC). Of these 77 patients, 65 could be evaluated for response and 74 for toxicity. Response rates were 65% in the primary organs (62% in the renal pelvis and ureter, 67% in the bladder), 68% in the lymph nodes, 60% in the lung, 25% in the bone and 14% in the liver. Complete responses were noted in 11 patients (17%) and partial responses in 26 patients for an overall response rate of 57% (95% confidence limits 45 to 69%). The median durations of response were 11 months for complete response patients and 7 months for partial response patients. Of the 65 patients 20 (31%) are alive, and 1-, 2-, and 3-year survival rates were 65%, 37%, and 25%, respectively. While survival rates of responders were higher than those of nonresponders with a statistical significance until 15 months, no significant differences were observed in survival rates between these two groups in the subsequent period. The M-VAC regimen was used for 15 patients as a neoadjuvant chemotherapy. Of the 15 patients, 8 responded and primary organs were preserved in 6 of the 8 responders. Histological effects classified according to Oboshi-Shimosato's criteria were G.I in 9, G.IIA in 3, G.IIB in 1, and G.IVC in 2. There were no significant differences in survival rates according to responses and histological effects. Factors related to response were analyzed with a multiple logistic regression model on 54 patients treated with intravenous administration of drugs and whose histological type was transitional cell carcinoma. The analysis results indicate that the presence of distant metastases is an important factor in predicting poor efficacy. Sixteen of 74 patients (22%) had white blood cell count of less than 1,000 cells per mm3 in the first cycle, while the decrease of platelet count was mild in degree compared with that of the white blood cell count. Patients with elevations of serum creatinine, GOT, and GPT were low in frequency, and toxic symptoms were controllable. Factors significantly related to the occurrence of side effects were sex, performance status, prior radiotherapy, prior chemotherapy, and the method of drug administration. Among these factors, prior radiotherapy was related to severe decrease of white blood cell count. While an excellent overall response rate was provided with the M-VAC regimen, disadvantages of the present regimen were low effectiveness in the bone and liver, and short duration of response.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) in advanced urothelial cancer--analysis of efficacy and toxicity]. 177 Jul 1

Gestational choriocarcinoma metastasizes rapidly, in which process the vasoactive prostanoids may be significant. We therefore compared the urinary excretion of prostacyclin and thromboxane A2 (TxA2) metabolites in 19 women with gestational choriocarcinoma and 20 healthy age-matched women by assessing spot urine samples for 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and 2,3-dinor-6-keto-prostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha) (degradation products of prostacyclin) as well as for thromboxane B2 (TxB2) and 2,3-dinor-TxB2 (degradation products of TxA2) by high-pressure liquid chromatography, followed by radioimmunoassay; the data were related to urinary creatinine concentration. The urinary output of 6-keto-PGF1 alpha [29.56 +/- 7.0 versus 25.08 +/- 3.91 ng/mmol creatinine (SE)] in patients with choriocarcinoma was normal, but that of 2,3-dinor-6-keto-PGF1 alpha in cancer patients was higher than in controls (24.44 +/- 5.20 versus 14.84 +/- 1.94, P less than 0.02), as was that of TxB2 (22.72 +/- 4.69 versus 9.69 +/- 1.52, P less than 0.001) and 2,3-dinor-TxB2 (114.21 +/- 30.81 versus 51.81 +/- 10.40, P less than 0.01). The ratio of net prostacyclin output (6-keto-PGF1 alpha plus 2,3-dinor-6-keto-PGF1 alpha) to the net TxA2 output (TxB2 plus 2,3-dinor-TxB2) in cancer patients [0.52 +/- 0.1 (SE)] was lower (P less than 0.03) than in the controls (0.83 +/- 0.1), and in an inverse relation (r = -0.54, P less than 0.05) to the scoring index of poor prognosis for the disease. We conclude that the prostanoid excess in gestational trophoblastic disease, as evidenced for the first time in this study, may originate from choriocarcinoma cells, or may be a paraneoplastic phenomenon, and we conclude also that TxA2 excess may contribute to the tumor growth and/or formation of metastases.
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PMID:Urinary excretion of degradation products of prostacyclin and thromboxane is increased in patients with gestational choriocarcinoma. 186 36

The consultants all agree to treat this patient who has a seemingly poor prognosis. However, they disagree as to the method and order of treatment. A patient's nutritional status is taken seriously by all 3 experts, although no one would delay surgery to correct a patient's weight loss. Drs. Komisar and Miller consider a weight loss of 10% significant and prefer to assess a patient with lymphocyte counts, serum albumin and transferrin levels, and creatinine/height index. Dr. Osguthorope follows serum hemoglobin, transferrin, prealbumin, and albumin levels. All the experts prefer an enteral route for weight gain. With regard to diagnosis, the experts agree that endoscopy plays an important role in tumor staging. Drs. Komisar and Osguthorpe believe that a tracheotomy should be performed prior to endoscopy. Dr. Miller would prefer intubation with an endotracheal tube but if there were any question of safety, he would proceed with a tracheotomy under local anesthesia. Confirming the histology of the pulmonary lesion is important. Dr. Komisar would proceed with flexible bronchoscopy and if tissue could not be obtained with this method he would obtain a fine-needle biopsy. He believes that if the histology matches that of the larynx, the pulmonary lesion is a metastasis. Dr. Osguthorpe would also obtain a needle biopsy of the lung lesion. If no other lesions are seen on the CT, he would consider this a second primary. Dr. Miller states that unless the histologies are different, the question of primary vs metastatic disease is unanswerable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Obstructing laryngeal carcinoma with a simultaneous lung lesion. 186 41


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