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)

EOE-13 was infused directly into the hepatic artery through a surgically implanted hepatic artery infusion pump in a patient with liver metastases. A computed tomographic scan obtained after EOE-13 infusion accurately showed the perfusion pattern of the implanted catheter. It also demonstrated the hepatic metastases more clearly than scintigraphy with 99mTc-macroaggregated albumin. EOE-13 may prove useful for the evaluation of hepatic perfusion patterns in patients receiving hepatic artery infusion chemotherapy.
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PMID:Intraarterial administration of EOE-13 for the CT evaluation of hepatic artery infusion chemotherapy. 632 56

The effect of brain implants of Walker 256 carcinosarcoma tumour cells on the integrity of the blood-brain barrier was examined in rats using labelled albumin, horseradish peroxidase and trypan blue. Barrier integrity was intact within 1 hour of implantation but was gradually reduced within the tumour after 3.5 days. This was related to alterations in the fine structure of the tumour capillaries. Dissociated tight junctions were apparent within the tumour centre, but no fenestrated endothelium or gap junctions were observed by electron microscopy.
Clin Exp Metastasis
PMID:Blood-brain barrier integrity and host responses in experimental metastatic brain tumours. 654 1

Magnetically responsive albumin microspheres containing doxorubicin hydrochloride were selectively localized in Yoshida sarcoma tumors. Tumors were implanted subcutaneously in the tail of Holtzman rats and allowed to grow to at least 200 mm2 size before initiation of experimental treatment. Drug-bearing microspheres at a dose level of either 0.5 or 2.5 mg/kg were infused proximal to the tumor via the ventral caudal artery. A bipolar permanent magnet was placed adjacent to the tumor during the infusion to effect localization. Control animals were treated with free doxorubicin infused intra-arterially at 5.0 mg/kg or 0.5 mg/kg. In other test groups animals received placebo microspheres localized in the tumor via influence of the external magnetic field, or drug-containing microspheres were infused without utilization of the magnet to effect localization. Of the 22 animals receiving magnetically localized doxorubicin microspheres 17 had total histological remission of the tumor. The remaining animals demonstrated marked tumor regression representing as much as 500-600 mm2 decrease in tumor size. While no deaths or metastases occurred in the groups receiving localized drug, animals treated with free doxorubicin, placebo microspheres or non-localized doxorubicin microspheres exhibited a significant increase in tumor size with metastases and subsequent death in 90-100% of the animals. No significant differences were noted in tumor regression/remission data between the 0.5 and 2.5 mg/kg dose levels of magnetically localized doxorubicin spheres. These results represent a significant advance in targeted chemotherapy in that 77% of the animals in the magnetically localized doxorubicin microsphere treatment groups exhibited total remission after only one regimen of drug therapy.
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PMID:Selective targeting of magnetic albumin microspheres containing low-dose doxorubicin: total remission in Yoshida sarcoma-bearing rats. 668 71

Although common in Japan, early gastric cancer (EGC = gastric adenocarcinoma confined to the mucosa and submucosa of the stomach, with or without regional lymph node metastases) is thought to be an infrequent occurrence in the United States. However, a review of all "curative" resections for carcinoma of the gastric body and antrum at the University of Virginia between 1974 and 1982 revealed EGC in five of 31 patients (16%). The purpose of the present study was to compare EGC to more advanced gastric cancer (ADV; n = 26) to determine whether any presenting historical, laboratory, x-ray, or endoscopic features distinguished the two groups before surgery and to ascertain whether postoperative survival in the United States mimicked the Japanese experience. All surviving patients were contacted, all charts were abstracted, all pathologic specimens were reexamined, and all radiographs were reviewed blindly by an experienced radiologist. Statistical evaluation was accomplished using Kaplan-Meier plots, chi square analysis, and unpaired "t" tests, as appropriate. At presentation, patients with EGC were younger (44 +/- 6 vs. 67 +/- 2 years, p less than 0.01) with higher admission albumin levels (4.1 +/- 0.2 vs. 3.7 +/- 0.1 mgm/dl, p less than 0.01). Although not significantly different, admission hemoglobin tended to be higher (41 +/- 2 vs. 35 +/- 2%), the incidence of weight loss tended to be less (40 vs. 65%), duration of symptoms tended to be longer (21 +/- 11 vs. 8 +/- 3 months), and tumor diameter tended to be smaller (1.7 +/- 0.6 vs. 5.8 +/- 0.7 cm) in EGC. No differences were apparent with respect to endoscopic or radiographic appearance, tumor location (greater than 70% antrum), presence of regional lymph node metastases (EGC = 2/5; ADV = 20/26), or type of resection (subtotal gastrectomy in 4/5 EGC, in 19/26 ADV). On median 5-year follow-up, however, survival with EGC has been 100%. In contrast, the Kaplan-Meier estimate of 5-year survival in ADV is 15% (42% with muscularis invasion, 0% with serosal invasion, 12% with extra-gastric spread; p less than 0.01 vs. EGC). One suture line recurrence in EGC was successfully treated by re-resection. No ADV patient with recurrence survives (p less than 0.01). Thus, EGC behaves similarly in the United States and Japan; for example, prognosis is excellent even in the presence of lymph node metastases. Inability to distinguish EGC from ADV before surgery justifies an aggressive surgical approach to all patients with resectable gastric neoplasms.
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PMID:Early gastric cancer. 672 9

A Phase I trial of tricyclic nucleoside phosphate (1,4,5,6,8-pentaazaacenaphthylene-3-amino-1, 5-dihydro-5-methyl-1-beta-D-ribofuranosyl 5'-phosphate ester; NSC 280594) was conducted using a 5-day continuous infusion schedule. Thirty-seven patients with advanced cancer were entered on the study, of whom 33 patients were evaluable for response and toxicity. Dose levels ranged from 10 mg/sq m/day X 5 days to 40 mg/sq m/day X 5 days. Initially, courses were repeated every 3 to 4 weeks. As cumulative toxicity became manifested, the interval between courses was changed to every 6 weeks. Major toxicities included hyperglycemia, hepatotoxicity, and thrombocytopenia. Patients with a prior history of diabetes mellitus, extensive radiation therapy, or significant liver metastases were prone to severe toxicity. Other toxicities noted were nausea and vomiting, abdominal discomfort, anemia, and reduction in serum calcium, phosphorus, and albumin levels. Rare side effects included hypertriglyceridemia, hyperamylasemia, diarrhea, and stomatitis. Antitumor activity observed include improvement in s.c. metastases in a patient with papillary thyroid carcinoma, stabilization of disease in a patient with mesothelioma, and mixed responses in three patients (colon cancer, sarcoma, and tonsillar squamous cell cancer). Recommended schedule for Phase II studies is 20 mg/sq m/day for 5 days every 6 weeks.
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PMID:Phase I study of tricyclic nucleoside phosphate using a five-day continuous infusion schedule. 674 83

The direct and indirect immunofluorescent methods were used to demonstrate the serum proteins in vasogenic brain edema on paraffin embedded formalin fixed human brains with carcinoma metastases. Applying these techniques extravasated albumin was detected within the tumor and in the surrounding neuropil. In the remote part of the peritumorous area the cytoplasma of neurons and astrocytes were stained specifically. The specific immunostaining clearly demonstrates the plasma origin of proteins in human peritumorous edema similarly to the experimental vasogenic brain edema. The immunofluorescent technique seems to be very useful to investigate the human brain edema on necropsy material as well.
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PMID:The application of immunofluorescent antibody method in research of human brain edema. 676 64

Basic lipophilic drugs such as propranolol and lidocaine are strongly bound by alpha(1)-acid glycoprotein, also called orosomucoid. Although the liver is known to rapidly clear plasma protein-bound propranolol or lidocaine, it is generally regarded that peripheral tissues, such as brain or heart, are only exposed to the small fraction of drug that is free or dialyzable in vitro. The "free drug" hypothesis is subjected to direct empiric testing in the present studies using human sera and an in vivo rat brain paradigm. Serum from 27 human subjects (normal individuals, newborns, or patients with either metastatic cancer or rheumatoid arthritis) were found to have up to a sevenfold variation in orosomucoid concentrations. The free propranolol or lidocaine as determined in vitro by equilibrium dialysis at 37 degrees C varied inversely with the orosomucoid concentration. Similarly the rate of transport of propranolol or lidocaine through the blood-brain barrier (BBB) was inversely related to the existing serum concentration of orosomucoid. However, the inhibition of rat brain extraction of drug by orosomucoid in vivo was only about one-fifth of that predicted by free drug measurements in vitro. This large discrepancy suggested orosomucoid-bound drug was readily available for transport into brain in vivo. Studies using purified human orosomucoid in the rat brain extraction assay also showed that orosomucoidbound propranolol or lidocaine is readily transported through the BBB. Conversely, albumin-bound propranolol or lidocaine was not transported through the BBB. The studies using albumin provide evidence that the in vivo rat brain paradigm used in the present investigations is capable of confirming, when possible, predictions made by the "free drug" hypothesis. These data suggest that the amount of circulating propranolol or lidocaine that is available for transport into a peripheral tissue such as brain is not restricted to the free (dialyzable) moiety but includes the much larger globulin-bound fraction. Therefore, existing pharmacokinetic models should be expanded to account for the transport of protein-bound drugs into peripheral tissues similar to what is known to occur in liver.
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PMID:Transport of propranolol and lidocaine through the rat blood-brain barrier. Primary role of globulin-bound drug. 683 93

Liver biomatrix contains a group of connective tissue components needed for attachment, survival, and maintenance of liver-specific functions of adult rat hepatocytes in culture. An acidic extract of liver biomatrix that contains a group of glycoproteins can replace intact biomatrix in promoting attachment and survival of hepatocytes. However, except for albumin synthesis, liver-specific functions have not been tested. Acidic extracts of biomatrices prepared from heart, kidney, lung, and spleen (heterologous) contain a similar group of glycoproteins, but differ with respect to liver glycoproteins in their capacity to sustain hepatocyte binding. Normal hepatocytes attach poorly to heterologous glycoprotein extracts, although regenerating and tumoral hepatocytes attach to liver glycoproteins and adhere equally well or with greater efficiency to heterologous glycoprotein extracts. The increased efficiency of hepatocytes to attach to kidney biomatrix-derived glycoproteins showed a linear correlation with the decreased glucagon binding capacity of their isolated plasma membranes. An epithelioid cell-line derived from kidney (MDCK) attached with higher efficiency to kidney than to liver glycoproteins. These results suggest that biomatrices may contain specific glycoproteins needed for attachment and survival of their epithelial cells. This specificity is lost during the proliferative state of regenerating and tumoral hepatocytes and could be important in the general mechanism of tumor dissemination and metastases.
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PMID:Abnormal matrix recognition by Morris hepatomas correlates with low glucagon binding capacity. 684 Jun 76

The level of blood albumin fucose in healthy subjects and cases of non-tumor pathology and benign tumors of the uterus and ovaries was found to be I nmol of fucose/10 nmol of human serum albumin or lower, whereas in patients with malignant tumors of different localizations it was 4-7 times as high. The highest levels were recorded in patients with primary hepatic cancer and hepatic metastases. The test may be used in differential diagnosis of tumor lesions of different localization as well as for assessment of tumor progression.
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PMID:[Serum albumin fucose in cancer patients]. 689 Nov 43

Magnetically responsive albumin microspheres containing doxorubicin and magnetite (Fe3O4) were selectively targeted to Yoshida sarcoma tumors in rats by utilizing an extracorporeal magnet. Tumor cells were inoculated subcutaneously in the tail of rats, and the tumors were allowed to grow to an average size of 9 X 45 mm prior to initiating treatment. Drug-bearing microspheres (0.5 mg of doxorubicin per kg of body weight) were infused proximal to the tumor through the ventral caudal artery while the tumor was exposed to an external magnetic field of 5500 Oe for 30 min. Control animals received free doxorubicin administered either intravenously (5 mg/kg) or infused intraarterially (5 and 0.5 mg/kg), drug-bearing microspheres infused intraarterially (0.5mg/kg), without the external magnet, or placebo microspheres with magnetic localization. Of the 12 animals treated with a single dose in the experimental group, 9 exhibited total remission of the tumor, representing a disappearance of tumors as large as 60 mm in length. Marked tumor regression was observed in the remaining three rats, and no deaths or metastases occurred in the experimental group. In contrast, significant increases in tumor size with widespread metastases occurred in all control groups and most rats died. These experiments indicate that targeting of oncolytic agents to solid neoplasms by magnetic microspheres may be a means of increasing the efficacy and decreasing the toxicity of antitumor agents.
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PMID:Tumor remission in Yoshida sarcoma-bearing rts by selective targeting of magnetic albumin microspheres containing doxorubicin. 694 Dec 58


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