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)

Little is known about drug distribution in tumor metastases or in the liver after hepatic arterial infusion. This information is important for planning strategies to enhance tumor drug uptake and to improve tumor response to therapy. Dye injection studies have demonstrated hepatic tumor vascular supplies in an anatomic manner, but offer no physiologic data. To evaluate hepatic drug distribution in patients with metastases to the liver and colon and rectum (6-3H) 5-fluorodeoxyuridine (FUdR) and 99m-technetium (TC) macroaggregated albumin (MAA) were infused through the hepatic artery prior to lobectomy of the right hepatic lobe in three patients and before wedge resection of a metastasis in one patient. Forty to 100 specimens of the tumor and liver taken at biopsy were assayed in order to map drug and albumin distribution. Nuclide scanning of the specimen was performed upon two patients. A linear relationship between levels of 3H (representing fluoropyrimidine metabolites) and 99mTc (representing blood flow) was demonstrated in both the tumor (correlation coefficients 0.69 to 0.87, p less than 0.01) and liver (correlation coefficients 0.76 to 0.90, p less than 0.001). The liver immediately adjacent to the tumor retained substantially more 99mTc-MAA than either the tumor itself or liver remote from the tumor, as demonstrated by both nuclide scanning and tissue biopsies. The rim of the liver adjacent to the tumor with enhanced 99mTc uptake had a different histologic appearance from a "normal" liver at a distance from the tumor in all instances. A radionuclide hepatic scan showing increased tumor uptake of 99mTc-MAA after arterial injection predicts an increased likelihood of tumor response to treatment. The results of this study demonstrate for the first time, in human beings, that increased 3H-FUdR uptake occurs in portions of the tumor which retain more 99mTc-MAA and explains the capacity of the arterial 99mTc-MAA perfusion scan to predict tumor response in the treatment of metastases to the liver and colon and rectum.
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PMID:Distribution of fluorodeoxyuridine uptake in the liver and colorectal hepatic metastases of human beings after arterial infusion. 295 82

The influence of a variety of clinical and biochemical parameters on the activities in serum of ribonuclease (RNAse) selective for polycytidylic acid (RNAse C) were examined in 90 adult patients with cancer. The clinical data base determined on each patient included: RNAse C level, carcinoembryonic antigen (CEA) level, age, sex, race, presence (or absence of metastases, type of cancer, site of metastasis, renal function blood urea nitrogen [BUN], creatinine), hepatic function (bilirubin, alkaline phosphatase), and nutritional status (percent ideal body weight, percent weight loss, and albumin). Common tumor types studied included: colon (21), lung (18), breast (15), and hepatocellular carcinoma (10). For comparison, 175 nonmalignant control patients were studied to establish the normal range for RNAse. In patients with cancer, RNAse levels were increased in 57% and CEA levels were above 10 ng/dl in 36%. Although patients with BUN greater than 25 mg/dl or creatinine greater than 1.5 mg/dl were not entered on the study, nonetheless, RNAse was significantly (P less than 0.05) associated with both BUN and creatinine. Nutritional status also had an important influence on RNAse levels as both percent weight loss and percent ideal body weight were significantly (P less than 0.05) associated with circulatory RNAse: weight loss resulted in higher RNAse levels. These results account in part for the increased RNAse levels seen in those malignant conditions such as pancreatic and lung cancer commonly associated with weight loss in advanced stage. The possibility that circulatory RNAse C determination will provide a sensitive means for assessing nutritional status in cancer patients will require prospective evaluation.
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PMID:Influence of nutritional status on circulatory ribonuclease C levels in patients with cancer. 298 Nov 45

The discriminative ability of several skeletal and tumour markers was assessed in 102 patients with prostatic disease. These comprised serum acid and alkaline phosphatase, serum albumin and osteocalcin, urinary excretion of calcium, hydroxyproline and 6-oxo prostaglandin F1 alpha. None of the tests was of value in distinguishing patients with benign prostatic disease from those with tumour not involving the skeleton. Values of serum osteocalcin, urinary excretion of calcium and urinary 6-oxo prostaglandin F1 alpha failed to discriminate significantly between patients with or without metastases. The remaining four markers were compared by decision matrix analysis and receiver operating characteristic (ROC) curves. Serum alkaline phosphatase provided the most sensitive marker of skeletal metastases (80.5%), followed by serum acid phosphatase (80%), hydroxyproline (68%) and albumin (30%). ROC analysis suggested that alkaline phosphatase conformed most closely to the "ideal marker" with highest specificity and sensitivity.
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PMID:Biochemical markers and skeletal metabolism in carcinoma of the prostate. Use of decision matrix theory and ROC analysis. 300 34

Between October 1983 and January 1986, sixteen patients with inoperable liver metastases from colorectal carcinomas were treated by single or cyclical intraarterial chemotherapy introduced either through an angiographic catheter or by means of a subcutaneously implanted access point (Port-A-Cath). Before each treatment cycle, the position of the catheter and the state of the vessels was examined by subtraction angiography in order to avoid complications and to confirm that the cytostatic agents were actually perfusing metastases, as shown by angio-CT. The complementary nature of the information obtained by these methods and their superiority over scintigraphy with 99mTc macroaggregated albumin particles is documented and the most frequent complications of regional tumour therapy are described.
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PMID:[Angiographic and computed tomographic findings in intra-arterial cytostasis of colorectal liver metastases]. 302 48

Intra-arterial chemoembolization using mitomycin C microsphere (MMC MS) was carried out both for VX-2 tumor-bearing rabbits and for 19 patients with inoperable hepatic cancer. MMC MSs contain 5% MMC in albumin as a biodegradable drug carrier and an average diameter is 45 +/- 8 microns. VX-2 tumor, implanted into the hind legs of the rabbits, was treated intraarterially when it grew up to 2 cm in diameter. Tumor growth was compared with the other treated groups such as control, conventional MMC or blank microsphere; and MMC concentrations in the peripheral blood, femoral vein blood and muscles of the hind legs were measured after treatment. Tumor growth in the MMC MS group was remarkably retarded, but the other groups had no retardation. MMC concentrations of blood and muscle dropped below the assay limitation within 2 hours after conventional MMC injection, but in the animals treated with MMC MS, those showed the sustained drug release over for 6 hours. Fifteen patients with unresectable hepatic malignancies received intra-arterial hepatic infusion using conventional MMC, while 19 patients were treated by MMC MS infusion. Tumor regression in the 19 patients with MMC MS was seen in 42% (8/19), while that in the 15 with conventional infusion in 33% (5/15). Serum CEA levels in 12 patients with metastatic cancer decline from 57.7 +/- 72.2 ng/ml to 16.5 +/- 21.6 ng/ml 2 weeks after MMC MS treatment. However, those in 10 patients given conventional infusion dropped from 24.0 +/- 18.1 ng/ml to 17.4 +/- 18.0 ng/ml. The survival duration for patients given conventional infusion was 6.7 +/- 2.8 months, but that with MMC MS prolonged to 14.1 +/- 8.9 months. The MMC MS treatment for metastatic hepatic cancer had superiority to the conventional infusion treatment at p = 0.0040 in survival rate.
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PMID:[Intra-arterial chemoembolization with albumin microspheres including mitomycin C in inoperable hepatic cancer]. 303 95

Growth of the murine hepatoma H6 was significantly suppressed by amiloride, a sodium influx inhibitor. Primary tumor growth inhibition was augmented by loading the drug into cross-linked albumin carriers, but lung metastases were enhanced. These results emphasize the importance of using metastatic tumor models when testing new drugs and/or alternative modes of drug delivery.
Clin Exp Metastasis
PMID:Enhanced tumor metastases upon drug delivery in cross-linked albumin beads. 308 52

Kazusamycins A and B and leptomycin B have a structure characteristic of an unsaturated, branched-chain fatty acid with a terminal delta-lactone ring, and show antibacterial activity on some kinds of fungi. Kazusamycin A (KZM-A) showed cytotoxic activity on mammalian cells at very low concentrations (ng/ml) in vitro. The antibiotic inhibited not only the growth of transplantable murine tumors and their metastases to the lung but also human mammary tumors inoculated into nude mice. KZM-A became immediately distributed to the main organs of mice, and a certain quantity of the antibiotic was inactivated by binding to high-molecular-weight substances such as albumin. A large quantity of KZM-A was carried to the liver and excreted into the bile, but was then reabsorbed by the small intestine. The growth of tumor metastases (L5178Y cells) in the liver was suppressed by KZM-A. The antibiotic induced severe diarrhea by causing necrosis and/or lysis of the mucous membrane of the small intestine. In contrast to this, the degree of myelotoxicity was relatively slight. The active site of the fatty acid of KZM-A appeared to consist of conjugated double bonds, carboxylic acid and hydroxyl moieties.
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PMID:[Studies on the new antibiotic kazusamycin and related substances]. 310 61

Between June 1973 and November 1980, 1,171 patients with metastatic breast cancer were treated with various doxorubicin-containing regimens at our institution (M.D. Anderson Hospital and Tumor Institute, Houston). Retrospective analysis of all 233 cases (20%) with liver metastases was done to correlate various clinical and biochemical characteristics with response to treatment, survival, and causes of death. A similar analysis was performed for 58 consecutive patients with liver metastases treated at this hospital between December 1955 and December 1957 with hormone therapy or single-agent chemotherapy. Objective responses were observed in 132 of 233 patients (57%) treated with combination chemotherapy. The median survival was 14 months in the 1970s and 5 months in the 1950s. Among patients who had liver metastases at the time of initial diagnosis of breast cancer, survival was longer for the group treated with combination chemotherapy. All cases were classified according to the number of organ sites involved by metastases. Patients with only liver metastases, or liver plus bone lesions had the longest survival. Other clinical and biochemical factors that correlated significantly with longer survival were: no prior chemotherapy, performance status of 1 to 2, absence of ascites, normal bilirubin and lactic dehydrogenase (LDH), SGOT less than or equal to 2 times normal and albumin greater than 4.5 g/dL. The main cause of death was multiorgan failure, with only 20% of patients dying of liver failure. The present study shows that the presence of liver metastases in breast cancer is not by itself an ominous factor. Most patients respond to therapy, and significant palliation with extended survival is possible for several prognostic subgroups. Further improvement in length and quality of survival is expected with earlier diagnosis.
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PMID:Clinical course of breast cancer patients with liver metastases. 310 83

Liver angiography and liver perfusion scintigraphy with Tc-99m-labeled macroaggregated albumin (MAA) were performed in 36 patients with liver metastases from colorectal cancer prior to continuous 5-fluorouracil hepatic artery infusion (HAI) hemotherapy. Of the 26 patients showing metastases on arteriogram, five revealed increased tumor vascularisation, five had normal vascularisation, and 16 showed decreased vascularisation of the metastases relative to liver. In liver perfusion scintigraphy, 15 of the 36 patients showed increased perfusion of the metastases, four had normal perfusion, and 17 had decreased tumor perfusion. The observed differences in survival in the different groups were not statistically significant: patients survived 15 months in the group with increased tumor vascularisation, 8 months for normal vascularisation, and 14 months for decreased tumor vascularisation; survival was 28 months for the group of increased, and 13 and 14 months for the normal and decreased tumor perfusion groups respectively. Also, response rates with 80%, 40%, and 75% responders in the group of increased, normal, and decreased tumor vascularisation, respectively, and 80%, 50%, and 59% responders in the group of increased, normal, and decreased perfusion, respectively, were not significantly different. These results indicate that there is no possibility to discriminate potential responders from nonresponders by results of liver angiography or perfusion scintigraphy.
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PMID:Results of liver angiography and perfusion scintigraphy do not correlate with response to hepatic artery infusion chemotherapy. 317 94

Seventy-eight patients with cytologically and/or histologically confirmed prostatic cancer were randomly allocated to orchidectomy (ORX, n = 37) or combined intramuscular and oral estrogen treatment (ESTR, n = 41). Serum levels of testosterone (T), 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, total estrone (tE1; sum of unconjugated and conjugated estrone, greater than or equal to 85% estrone sulfate), cortisol, luteinizing hormone, follicle-stimulating hormone, prolactin, growth hormone, sex hormone-binding globulin (SHBG), and albumin were determined prior to treatment and 12, 24, and 36 months after initiation of treatment. Fifty patients responded to treatment or had stable disease, and 28 did not respond (12 in the ORX and 16 in the ESTR group). There was no association between pretreatment hormone or protein levels and outcome of the treatment, neither in the total material nor within either of the two treatment subgroups. Significantly higher pretreatment levels of cortisol and prolactin and significantly lower levels of T, tE1, and albumin and a significantly lower T/SHBG-ratio (index on biologically active T) were found in patients with metastatic disease, compared with the patients without metastases. There was no association between testicular or adrenal androgens, SHBG, T/SHBG, and albumin values during treatment and the clinical outcome. The differences found between metastatic and nonmetastatic disease probably simply reflect the more stressful and catabolic condition and generally poorer health in patients with disseminated malignant disease. Furthermore, the study does not lend any support to the hypothesis that indicates an important role of adrenal "rest androgen" in prostatic cancer tumor growth.
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PMID:Prognostic value of serum hormone concentrations in prostatic cancer. 321 6


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