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)

Cell surface carbohydrate structures acting as ligands for tissue specific mammalian lectins have been implicated in cell-cell interactions during embryogenesis, lymphocyte homing, and tumor cell metastasis. In this report, we provide evidence that beta 1-4 linked galactose (Gal) residues in N-linked oligosaccharides on the surface of blood born tumor cells serve as a ligand for binding to microvascular endothelial cells. D36W25, a class 1 glycosylation mutant of the MDAY-D2 lymphoreticular tumor cell line, lacks sialic acid and Gal in cellular glycans due to a defect in the Golgi UDP-Gal transporter. Using UDP-Gal and bovine galactosyltransferase in vitro, beta 1-4 Gal was restored to the surface of the cells and 70% of the galactosylated glycans persisted for 8 h in vitro at 37 degrees C. Compared to mock-treated D36W25 cells, galactosylated D36W25 cells showed an 80% increase in binding to microvascular endothelial cell monolayers in vitro. The enhanced binding of galactosylated D36W25 cells to endothelial cell was inhibited by the addition of lactosamine-conjugated albumin to the assay. Consistent with these observations, swainsonine and castinospermine, two inhibitors of N-linked processing that result in loss of lactosamine antennae inhibited the binding of wild-type MDAY-D2 cells to endothelial cells in vitro. Injection of radiolabeled tumor cells into the circulation of syngeneic mice, showed that galactosylation of D36W25 cells resulted in 2-3 more tumor cells retained in the lungs and livers. In addition, galactosylation of D36W25 cells increased by 30-fold the number of visible liver metastases on inspection 4 wk after tumor cell injection. These results suggest that beta 1-4Gal-binding lectins on microvascular endothelial cells can contribute to retention and secondary tumor formation of blood born tumor cells. With the increasing availability of purified glycosyltransferases, reconstruction of a variety of carbohydrate sequences on the surface of class 1 mutants provides a controlled means of studying carbohydrate-lectin interactions on viable cells.
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PMID:Tumor cell surface beta 1-4-linked galactose binds to lectin(s) on microvascular endothelial cells and contributes to organ colonization. 211 22

A33 is a mouse immunoglobulin G2a (IgG2a) monoclonal antibody (mAb) that detects a heat-stable, protease- and neuraminidase-resistant epitope. The antigen is homogeneously expressed by virtually all colon cancers and in the colon mucosa but not other epithelial tissues. The biodistribution and imaging characteristics of iodine-131 (131I)-mAbA33 were studied in colorectal carcinoma patients with hepatic metastases. Antibody labeled with 2 to 5 mCi of 131I was administered intravenously (IV) 7 to 8 days before surgery at five dose levels, ranging from 0.2 mg to 50 mg, with three or more patients entered at each dose level. In addition, three patients received 2 mg 131I-mAbTA99 (an isotype-matched control mAb) together with 125I-mAbA33. Evaluation included whole-body imaging with a gamma camera, technetium-99 (99mTc)-human serum albumin blood pool scans, liver/spleen scans, abdominal computed tomographic (CT) scans, hepatic arteriograms, antibody pharmacokinetics, and assessment of antibody distribution in biopsied malignant and normal tissues. Selective mAbA33 localization to tumor tissue was demonstrated in 19 of 20 patients, and external imaging correlated with surgical inspection, pathologic examination, and tissue radioactivity. One week after antibody administration, tumor:liver ratios ranged from 6.9:1 to 100:1 and tumor:serum ratios from 4.1:1 to 25.2:1. 99mTc-albumin blood pool studies showed that liver metastases were hypovascular, emphasizing the selective localization of mAbA33 despite poor tumor-blood flow. Control mAbTA99 studies showed mAbA33 localization was antigen-specific; tumor:liver ratios were 2.3- to 45-fold higher for specific antibody. In metastatic lesions, radioisotope was localized primarily in the viable periphery; however, even the necrotic tumor core concentrated specific antibody. External imaging showed isotope visualization in some patients' large bowel; whether this represents specific antibody uptake or gastric iodine secretion is unclear.
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PMID:Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33. 223 Aug 77

To determine the incidence and causes of hypercalcaemia in a hospital population in Hong Kong, all 29,107 samples received in the laboratory in one year were analysed for plasma calcium and albumin, and samples with a plasma calcium concentration adjusted for albumin greater than 2.55 mmol/l were investigated. Plasma calcium greater than 2.55 mmol/l was found in 462 patients. Repeat samples were received from 302 of these and hypercalcaemia was confirmed in 183. The main causes of hypercalcaemia were malignancy (72.1 per cent), tuberculosis (6.0 per cent), and primary hyperparathyroidism (5.5 per cent). In the malignant hypercalcaemia group, carcinoma of lung was the most common (31.8 per cent) and carcinoma of breast was uncommon (3.0 per cent). Secondary deposits in bone were detected in 35 of the 122 solid tumours. In order to identify the mechanism of hypercalcaemia the contributions of renal tubular reabsorption and increased bone resorption to the plasma calcium concentration were calculated. Increased tubular reabsorption was the main contributor to hypercalcaemia in primary hyperparathyroidism and carcinoma of liver (none of whom had bony metastases) and it contributed significantly to hypercalcaemia in carcinoma of lung without bony metastases and carcinoma of oesophagus. We conclude that in Hong Kong (a) primary hyperparathyroidism is uncommon, (b) tuberculosis is an important cause and (c) humoral factors may be responsible for a relatively high proportion of cases of malignant hypercalcaemia.
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PMID:Incidence, causes and mechanism of hypercalcaemia in a hospital population in Hong Kong. 229 Sep 21

Hepatic resection of metastatic disease due to primary colorectal cancer provides a relatively safe and reliable method to control this otherwise fatal disease. At New York University 45 hepatic resections have been performed in 42 patients over the last fifteen years. Preoperative screening was performed by liver chemistry and intraoperative exploration in synchronous lesions and by liver chemistry, carcinoembryonic antigen, and computed tomography in metachronous lesions. Careful monitoring of fluid management, glucose utilization, and albumin requirements are essential for low postoperative morbidity and mortality. In major hepatic resections, changes in coagulation profile correlate with normalization of hepatic function as evidenced by decrease in serum bilirubin levels and increase bile production. The incidence of major operative morbidity was 17%; operative mortality was 4%. Hepatic resection gives the greatest possibility of extended survival, in our patients providing a 22% crude five year survival rate and a mean duration of survival of 33 months.
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PMID:Surgical resection for colorectal hepatic metastases. 236 16

Thirty-two patients with inoperable hepatic cancer underwent intra-arterial hepatic infusion using mitomycin C (MMC) and 5-fluorouracil (5-FU) or intra-arterial hepatic chemoembolization using heated albumin microspheres containing MMC with an average diameter 45 +/- 8 micron. Nineteen of the 32 patients received the MMC microsphere treatment and another 13 received the conventional infusion treatment, lasting for 3.4 months. The administered doses of MMC microspheres were 11.7 +/- 11.1 mg as MMC in the 12 with metastatic cancer and 6.9 +/- 2.1 mg as MMC in the 7 with hepatocellular cancer (HCC). On the contrary, the 13 patients who underwent conventional infusion had average doses of MMC 34.5 +/- 17.3 mg and of 5-FU 13.4 +/- 7.7 g, over 3.4 months. An objective tumor response was obtained in 13/19 (68.4%) under MMC microsphere chemoembolization, compared to 6/13 (46.2%) under the conventional infusion. The average level of CEA in the 12 with metastatic cancer, who underwent MMC microsphere therapy, dropped from 57.7 ng/ml to 16.5 ng/ml, while that in the 10 patients on conventional infusion dropped from 24.0 ng/ml to 17.4 ng/ml; that of alpha-fetoprotein dropped in all 7 with HCC on MMC microsphere chemoembolization, compared to a fall in 1/3 on conventional infusion. With the MMC microsphere treatment, 5 patients from colorectal cancer lived for 15.6 +/- 7.6 months, 2 are alive with a long life expectancy; and 7 patients from gastric or pancreatic cancer lived for only 9.3 +/- 3.3 months. In case of conventional infusion, 6 patients from colorectal cancer survived for 8.6 +/- 3.2 months; and 4 patients from gastric or gallbladder cancer survived for 6.0 +/- 1.0 months. The MMC microsphere treatment is superior at P = 0.059 in survival duration to the conventional infusion treatment. However, much the same survival occurred in 7 on MMC microsphere chemoembolization and 3 on continuous infusion.
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PMID:Biodegradable mitomycin C microspheres given intra-arterially for inoperable hepatic cancer. With particular reference to a comparison with continuous infusion of mitomycin C and 5-fluorouracil. 241 82

The passage of circulating tumor cells across the vascular wall is an important step in the evolution of cancer metastases. Since tumor cells attach preferentially to subendothelial matrix at sites of endothelial injury and retraction in vitro, we have used an established in vivo model of pulmonary endothelial damage to examine the effects of endothelial injury on the localization and metastasis of circulating tumor cells in vivo. C57BL/6 mice were given a single i.v. dose of bleomycin (120 mg/kg) or multiple i.p. injections (10 mg/kg, twice weekly for 6 wk). Five days after the single injection or 4 days after the last i.p. injection, 2 X 10(5) [131I] iododeoxyuridine-labeled fibrosarcoma cells or unlabeled cells were injected i.v. Two to 8 times as many labeled cells were found in the lungs of bleomycin-treated animals after 24 h. Two and 3 wk after injecting unlabeled fibrosarcoma cells, 1.4 to 5 times more metastatic lung colonies were counted in bleomycin-treated animals than in controls. Morphometric analysis of histological sections demonstrated that the percentage of lung area occupied by tumor in bleomycin-treated animals was between 4 and 16 times that of controls. Analysis of bronchoalveolar lavage fluids demonstrated 5-fold increases of total protein content and leakage of previously injected 125l-labeled albumin, indicating increased endothelial permeability. Electron microscopic examination of lungs of bleomycin-treated mice demonstrated endothelial retraction with exposure of the underlying basement membrane. Electron microscopy of [3H]thymidine-labeled tumor cells, located by autoradiography, demonstrated their attachment to exposed basal lamina. Data from these experiments in vivo support the hypothesis that endothelial damage can facilitate the metastasis of circulating tumor cells.
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PMID:Promotion of pulmonary metastasis in mice by bleomycin-induced endothelial injury. 241 35

Tumor-induced neovascularization is essential for invasion, metastases, and exponential growth of solid tumors. The authors studied the differences in macromolecular leakage from the neovasculature of a fast-growing, early-metastasizing tumor, the Walker 256 carcinosarcoma, and a slow-growing, nonmetastasizing tumor, a rat chondrosarcoma. A 1-mm3 piece of the Walker 256 carcinoma or the chondrosarcoma was implanted in the cremaster muscle of rats. Five days after surgery the cremaster muscle with the implanted tumor was placed in a special bath containing Krebs solution such that the circulation and nerves from the animal to the cremaster were intact. Fluorescein isothiocyanate-labeled rat serum albumin (FITC-RSA) was injected (intra-arterially) into each rat to permit visualization of the vasculature by fluorescent microscopy. A closed-circuit television system was used to quantitate macromolecular leakage as a change in interstitial fluorescent intensity. Data are given as a relative fluorescent intensity (mean +/- standard error of the mean) in an area of the cremaster with tumor-induced neovascularization. These studies demonstrated that the vasculature induced by rapidly growing Walker 256 carcinosarcoma leak albumin freely when compared with the vasculature induced by the slow-growing chondrosarcoma. Furthermore, there was a significant increase in fluorescent intensity (albumin leakage) in the Walker tumor from 1 minute (24 +/- 3.0) to 30 minutes (49 +/- 5.6). In the normal cremaster area there was a significantly lower fluorescent intensity in the interstitium and a very slight increase with time (4 +/- 1.5 at 1 minute vs. 7 +/- 1.4 at 30 minutes). One interpretation of these data is that the mechanisms responsible for protein leakage from the vasculature of the Walker tumor may be involved in the fast growth and metastases of this tumor as compared with slower-growing tumors such as the chondrosarcoma.
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PMID:Differential macromolecular leakage from the vasculature of tumors. 241 77

Variation in response rates to chemotherapy and survival in patients with hepatic metastases from colorectal carcinoma may be due to patient selection factors. The prognostic importance of 13 factors were analyzed in 112 patients with only hepatic metastases, who were eligible for hepatic artery infusional chemotherapy. When individually analyzed, six factors were found to significantly (less than 0.001) affect survival: the percentage of tumor involvement of the liver, assessed medically or surgically; initial serum albumin and lactic dehydrogenase; initial Karnofsky performance status; and weight loss. Patients with less than or equal to 30% liver involvement had a median survival of 24 months versus 10 months if they had greater than 30% involvement. There was a highly significant agreement between medical and surgical assessment of liver involvement (P = 0.0001). When the variables affecting survival were studied together by multivariable analyses, the most important factor was the medical assessment of liver involvement accomplished by evaluation of radionuclide liver scan and CTT scans. The next two most important factors in the model were the ability of the patient to obtain a tumor response and the presence or absence of weight loss. Only one factor helped predict response to chemotherapy, the type of perfusion seen on a 99Technetium-macroaggregated albumin (MAA) arterial flow scan. Forty-five percent of patients with good perfusion had a partial response while 13% of patients with poor perfusion had a tumor response (P = 0.006). We recommend that future studies, dealing with patients who have hepatic metastases from colorectal carcinoma and are eligible for hepatic arterial infusion, document and stratify for the following factors: the percentage of liver involvement, the presence or absence of weight loss, and the type of perfusion seen on MAA scans.
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PMID:Prognostic variables in patients with hepatic metastases from colorectal cancer. Importance of medical assessment of liver involvement. 252 70

Hepatic metastases of colorectal carcinoma demonstrate a dose response to chemotherapy. In animal studies hepatic arterial infusion of chemotherapeutic agents with degradable starch microspheres (DSMs) produces a redistribution of blood flow between tumor and liver and an increase in tumor drug levels. In this prospective clinical study in patients with colorectal metastases, we evaluated the effect of DSMs on liver and tumor levels of fluoropyrimidines after intraoperative administration through the hepatic artery. Fourteen patients underwent infusion of radiolabeled fluorodeoxyuridine, 14C-FUdR (0.15 mg/kg, 0.5 microCi/kg), followed 2 to 5 minutes later by infusion of 3H-FUdR (0.15 mg/kg, 1.0 microCi/kg) without (n = 3) or with (n = 11) DMS. Seven of the later patients underwent major hepatic resection and tissue mapping of drug distribution, and four patients underwent biopsy procedures to remove specimens of liver and tumor 5 minutes after microsphere infusion. Administration of DSMs with FUdR increased tumor drug levels as measured by 3H-FUdR (5.9 +/- 4.4 vs 17.1 +/- 9.4 nmol/gm, p = 0.07) without altering hepatic drug levels (35.7 +/- 10.9 vs 30.2 +/- 20.9 nmol/gm, p = NS) and significantly increased the tumor/liver drug ratio of tritiated fluoropyrimidines (0.16 +/- 0.09 to 0.63 +/- 0.13, p = 0.03). Fluoropyrimidine levels in tumor and liver correlated with blood flow as measured by technetium-99m macroaggregated albumin retention. Thus, hepatic arterial administration of DSMs in human beings enhances tumor FUdR levels and may be useful in increasing tumor cytotoxicity and decreasing systemic toxicity during regional hepatic infusion.
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PMID:Regional hepatic arterial infusion of degradable starch microspheres increases fluorodeoxyuridine (FUdR) tumor uptake. 252 47

Intra-arterial hepatic chemotherapy is effective in the treatment of liver metastases, and it has been used at the Gustave Roussy Institute since 1983. During laparotomy, arterial catheters are introduced usually into the gastroduodenal artery, and they are connected either to a subcutaneous access or to an implantable pump. Seventy-one patients with liver metastases from colorectal adenocarcinoma were examined by angioscintigraphy to evaluate the quality of liver perfusion. Our technique uses three radioactive compounds and makes it possible to obtain a standard liver scintigram with technetium 99-colloidal rhenium sulphur, a dynamic view of liver arterial perfusion by injection of pure technetium 99 pernechtate, and a static mapping of well-perfused territories after injection of technetium 99-labelled macroaggregated albumin. This technique is reliable to explain most of the problems encountered during intra-arterial hepatic chemotherapy. In our experience, the quality of perfusion was highly variable and had a prognostic value. Objective responses were more frequent in well-vascularized metastases (64 percent) than in metastases with hypoperfusion (36 percent). Survival was also better in the former case, with a median survival of 18 months as against 12 months (p = 0.028).
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PMID:[Control of perfusion by angioscintigraphy during hepatic intra-arterial chemotherapy]. 253 44


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