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)

With the use of a rat 13762 mammary adenocarcinoma tumor, we have examined the relationship between cellular fibronectin (FN) expression and ability to metastasize spontaneously to regional lymphatic and distant blood-borne sites. This model is based on the isolation and establishment of cell clones from primary parental tumor and from spontaneous metastases that show differing metastatic potentials when implanted s.c. into the mammary fat pads of syngeneic female Fischer 344/CRBL rats. Cellular FN expression was determined in tissue culture as well as primary and secondary tumor sites, utilizing: (a) indirect immunofluorescence microscopy with a specific anti-rat FN antibody (in vitro and in vivo grown cells); (b) competition radioimmunoassay for cell-released FN (in vitro grown cells); and (c) surface labeling by radioiodination-sodium dodecyl sulfate-polyacrylamide gel electrophoresis-autoradiography for cell surface-bound FN (in vitro grown cells). Tissue culture-grown parental tumor clones displayed FN at their cell surfaces. At confluency, they expressed higher quantities of FN at their peripheries and in fibrillar structures between adjacent cells and released greater amounts of this glycoprotein. Lung metastases-derived tumor clones released negligible amounts of FN by radioimmunoassay and failed to express detectable amounts of FN by indirect immunofluorescence and cell surface-labeling techniques. However, when parental tumor- and metastasis-derived clones of widely different metastatic potentials were carefully examined for FN expression and release, there was no obvious relationship between metastasis and FN expression or release in culture or display in tumors at primary or secondary sites. The results suggest that expression or release of FN per se is not a determinant of metastasis, although it may be a factor in certain steps of the metastatic sequence.
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PMID:Distribution of fibronectin on clonal cell lines of a rat mammary adenocarcinoma growing in vitro and in vivo at primary and metastatic sites. 730 9

We have studied the diagnostic potential of thallium 201 in cerebral metastases. Twenty-five patients with one or several metastases have been investigated with two tracers, 201T1 and sodium pertechnetate (99Tcm). With 201T1, all the cases gave a positive result within ten minutes of injection. In 88%, the definition was better, and in five cases (20%) small metastases which were invisible with 99Tcm could be demonstrated with 201T1. This radiotracer seems to promise greater diagnostic precision with an examination time of only 30 minutes.
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PMID:Diagnosis of cerebral metastases by thallium 201. 738 77

The antihistaminic over-the-counter drug methapyrilene hydrochloride, mixed with food at a concentration of 0.1 percent, was administered to 50 male and 50 female Fischer rats. A second group of 50 male and 50 female rats was given the same treatment together with 0.2 percent of sodium nitrite added to the food. Almost all of the rats in both groups developed liver neoplasms, mainly hepatocellular carcinomas and cholangiocarcinomas. The first rat died with a liver neoplasm at the 43rd week. Over 50 percent of the rats in both groups had metastases from the carcinomas of the liver to distant organs. Control rats treated with nitrite only, or untreated, did not develop liver neoplasms. There was no discernible effect of nitrite on the carcinogenicity of methapyrilene hydrochloride.
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PMID:Liver tumors induced in rats by oral administration of the antihistaminic methapyrilene hydrochloride. 740 48

An IgM lambda human tumor cell-reactive monoclonal antibody was developed that reacts with cells of ovarian cancer, colorectal cancer, breast cancer, and certain other malignancies. The monoclonal antibody AC6C3-2B12, which was obtained from a recent recloning, was purified from tissue culture supernatants and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-PAGE. An animal model was developed in which human tumors grew either as solid peritoneal metastases or as s.c. nodules utilizing the human colorectal carcinoma cell line SW620. The biodistribution of 111In-labeled IgM conjugate was studied after i.v. or i.p. administration in nude mice bearing an s.c. xenograft or peritoneal tumor lumps of a human colorectal carcinoma (SW620). IgM administered i.v. cleared rapidly from blood and was deposited mainly in the liver [50% injected dose/g (ID)/g)], pancreas (20% ID/g), and kidney (10% ID/g) at 24 h. Tumor deposition was low (< or = 1.0% ID/g) in the s.c. tumor xenograft. In contrast, high tumor targeting (29% ID/g) was found in peritoneal tumor lumps after i.p. administration of 111In-labeled IgM. The biological half-life of IgM in the tumor was 100 h. Long peritoneal residence time (t 1/2 = 67 h) and low liver uptake (7% ID/g) were observed after i.p. administration. Blood activity was < 1% of the injected activity. Tumor:normal organ ratios were high (range, 2-290) from 2 to 144 h after i.p. administration. Whole body autoradiograms at 24 h after i.p. 111In-labeled IgM administration confirmed the biodistribution results. In normal beagle dogs, 75% of the i.p.-administered 111In-IgM decayed in the peritoneal cavity. The majority of the remaining radioactivity was taken up by mediastinal lymph nodes. Biological half-life in both locations was approximately 137 h. The i.p. administration of intact, specific radiolabeled IgM provides prolonged retention of radioactivity in tumor, low normal tissue uptake, a long peritoneal residence time, and very limited spillover of IgM into the circulation. This approach offers a promising new method for the diagnosis and treatment of certain patients with peritoneal carcinomatosis.
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PMID:Preclinical analysis of intraperitoneal administration of 111In-labeled human tumor reactive monoclonal IgM AC6C3-2B12. 749 38

Sodium D-glucaro-delta-lactam (ND2001) inhibited spontaneous pulmonary metastases of the highly metastatic B16 melanoma variant with a maximal inhibition rate of 99.5%, and 6 of 7 animals remained metastasis-free. Likewise, ND2001 inhibited the spontaneous pulmonary metastases of both Lewis lung carcinoma (3LL) with a rate of 98.0% (3 of 5 animals remaining metastasis-free) and rat KDH-8 liver carcinoma with a rate of 82.5% (3 of 7 animals remaining metastasis-free), although it was unable to inhibit the metastases of mouse BMT-11 fibrosarcoma and rat SST-2 breast carcinoma. Pretreatment with ND2001 in vitro inhibited the pulmonary metastases of the B16 variant and 3LL cells, which indicates direct action upon the cancer cells. When the invasive activity of cancer cells was measured by the Boyden chamber method, the number of invading B16 variant or 3LL cells was reduced with maximal inhibition rates of 93.0% or 89.9%, respectively, but pretreatment with ND2001 failed to reduce the invasive activity of BMT-11 or SST-2 cells. ND2001 showed neither cytocidal nor antitumor activity. These results suggest that ND2001 inhibited pulmonary metastases at the invasive step into the basement membrane by directly changing some property of the tumor cells.
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PMID:Inhibition of pulmonary metastases and tumor cell invasion in experimental tumors by sodium D-glucaro-delta-lactam (ND2001). 773 8

The nuclear enzyme topoisomerase I (topo I) has been recently recognized as the target for the anticancer drug camptothecin (CPT; NSC 94600) and its derivatives. This drug has been reported to display effective antitumor effects on a variety of human tumor models xenografted in nude mice. However clinical studies of sodium CPT have revealed that the open-ring form of the drug is a poor inhibitor of topo I and much less potent antitumor agent than CPT lactone. However, the insolubility of CPT lactone makes it difficult to devise a suitable formulation for further clinical testing. In view of these observations, we report here the successful incorporation of CPT into a liposome-based drug delivery system (LCPT) composed of DPPC:Sph:CHOL:PI (2.4:6.6:1.0:0.05 M ratio) that can be used as a suitable formulation for clinical testing of the drug. Higher incorporation efficiency was observed when the total phospholipids:drug ratio = 40 and the cholesterol content = 1%. Image analysis of the CPT-containing liposomes with freeze-fracture electron microscopy has indicated that CPT significantly increased the interlamellar space of the vesicles as a result of its intercalation between lipid bilayers. This has occurred with no major disruptive effects on the bilayer structure. The in vitro drug release study in human serum was characterized by an initial rapid loss-of 50% of contents during 4 h, followed by a slow leakage of the remaining 50% of the total drug over a 20 h period. When tested for its antitumor activity on nude mice xenografted with human malignant melanoma and breast carcinoma, LCPT displayed effective antitumor activity with minimal host toxicity. For example, single i.m. injection of LCPT at 10 mg/kg has produced complete tumor regression to nude mice xenografted with CLO breast carcinoma. Likewise, similar results were obtained with the nude mice xenografted with human malignant BRO cells melanoma. These results appear to suggest that i.m. administration of liposome-incorporated CPT has considerable potential for the treatment of human neoplastic diseases, especially lymph node metastases.
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PMID:Antitumor effect of liposome-incorporated camptothecin in human malignant xenografts. 775 88

The authors examined 40 patients with malignant tumors of various histogenesis, sites and extent, as well as 5 patients with benign tumors and other non-tumorous diseases. They also studied their electroencephalography and peripheral blood lymphocytic and erythrocytic ultrastructure in metabolic alkalosis temporarily induced by intravenous sodium hydrogen carbonate. In cancer patients without late metastases, alkalosis caused a transient normalization of previously altered electroencephalography, erythrocyte disaggregation and substantially reduced the count of killer cells in small and middle lymphocytes. These findings suggest that patients with malignant neoplasms have a generalized intracellular acidosis which can be temporarily abolished by plasma alkalinization.
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PMID:[Characteristics of the effects of artificial alkalosis on electrical activity of the brain and ultrastructure of blood cells in oncologic patients]. 778 Mar 36

Migration plays an important role in the formation of tumor metastases. Nonetheless, little is known about electrophysiological phenomena accompanying or underlying migration. Previously, we had shown that in migrating alkali-transformed Madin-Darby canine kidney focus (MDCK-F) cells a Ca(2+)-sensitive 53-pS K+ channel underlies oscillations of the cell membrane potential. The present study defines the role this channel plays in migration of MDCK-F cells. We monitored migration of individual MDCK-F cells by video imaging techniques. Under control conditions, MDCK-F cells migrated at a rate of 0.90 +/- 0.03 microns/min (n = 201). Application of K+ channel blockers (1 and 5 mmol/liter Ba2+, 5 mmol/liter tetraethylammonium, 100 mumol/liter 4-aminopyridine, 5 nmol/liter charybdotoxin) caused marked inhibition of migration, pointing to the importance of K+ channels in migration. Using patch-clamp techniques, we demonstrated the sensitivity of the Ca(2+)-sensitive 53-pS K+ channel to these blockers. Blockade of this K+ channel and inhibition of migration were closely correlated, indicating the necessity of oscillating K+ channel activity for migration. Migration of MDCK-F cells was also inhibited by furosemide or bumetanide, blockers of the Na+/K+/2Cl- cotransporter. We present a model for migration in which oscillations of cell volume play a central role. Whenever they are impaired, migration is inhibited.
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PMID:Oscillating activity of a Ca(2+)-sensitive K+ channel. A prerequisite for migration of transformed Madin-Darby canine kidney focus cells. 816 66

The expression of metalloproteinases, such as type IV collagenase/gelatinase, enables tumor cells to degrade type IV collagen present in the basement membrane and correlates with metastatic potential of several tumor types. We found that increased levels of rat serum type IV collagenolytic activity are associated with increased 13762NF mammary adenocarcinoma metastases in lungs and lymph nodes of syngeneic rats. To investigate serum metalloproteinases responsible for type IV collagenolysis, we performed zymography and Western blot analysis of rat sera. A M(r) 92,000 progelatinase (progelatinase B, M(r) 92,000 type IV procollagenase, MMP-9) was detected on zymograms of rat sera within 16 days after intramammary fat pad inoculation of highly metastatic MTLn3 cells. The activated serum M(r) 92,000 progelatinase degraded sodium dodecyl sulfate-denatured type I and IV collagens but was not active on casein, albumin, hemoglobin, and immunoglobulin. Sera from rats with fat pad tumors and lung metastases formed from highly metastatic clones possessed greater than 7 times higher levels of serum M(r) 92,000 progelatinase than control sera or sera from rats bearing similar size fat-pad tumors of low or nonmetastatic clones. The results were confirmed by Western blot analysis of rat sera using rabbit anti-human M(r) 92,000 progelatinase antibodies. Similar results were obtained from the analysis of rat plasma samples. The serum and plasma M(r) 92,000 progelatinase levels correlated with the extent of metastases in the lung and lymph nodes. The results indicate that high levels of serum and plasma M(r) 92,000 progelatinase are associated with the presence of disseminated metastatic adenocarcinoma cells and suggest that this enzyme may facilitate the invasion of blood-borne tumor cells through vascular basement membranes.
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PMID:Serum and plasma M(r) 92,000 progelatinase levels correlate with spontaneous metastasis of rat 13762NF mammary adenocarcinoma. 824 39

There are a number of lines of evidence suggesting that transforming growth factor beta (TGF beta) has an important role in the control of intestinal growth and differentiation. In vivo localization studies show that TGF beta expression occurs predominantly in the differentiated non proliferating cells of the intestinal epithelium. The use of an antisense expression vector for TGF beta resulted in an increased tumorigenicity in an antisense-transfected cancer cell line. In vitro proliferation studies showed colorectal premalignant adenoma cells to be more sensitive to the growth inhibitory effects of TGF beta than colorectal cancer cells. Furthermore the conversion of an adenoma to a carcinoma was accompanied by a reduced response to the inhibitory effects of TGF beta. The acquisition of partial or complete resistance to the inhibitory effects of TGF beta may be an important late event in colorectal carcinogenesis. Of further interest is the possibility that clonal selection could occur even more rapidly in colorectal tumour cells which not only had lost response to TGF beta inhibition but produced TGF beta and were growth stimulated by it. This could have the advantage of not only inhibiting the growth of surrounding less malignantly advanced cells but of also escaping from their potential growth suppressive influence. Carcinogenesis is not, however, simply losing response to negative regulators of growth; the fully malignant cell has to acquire new characteristics of invasiveness and metastatic potential. Growth factors including TGF beta may have a role in the complex cascade of events leading to the activation of proteolytic enzymes which are involved in progression to an invasive phenotype. Cell proliferation in the large bowel, as well as being under the control of endogenous growth factors, is also under the influence of dietary components in the lumen such as the naturally occurring fatty acid sodium butyrate. Sodium butyrate at physiological concentrations induces apoptosis (programmed cell death) in colonic tumour cell lines. Since sodium butyrate occurs naturally in the colorectum, being produced by bacterial fermentation of dietary fibre, it may be involved in the control of cell death in human colorectal epithelium. This could, in part, explain the apparent protective effects of dietary fibre. Clonal evolution and tumour progression in colorectal carcinogenesis could therefore involve loss of response to endogenous growth factors such as TGF beta and an escape from the induction of programmed cell death by dietary factors.
Cancer Metastasis Rev 1993 Sep
PMID:Escape from negative regulation of growth by transforming growth factor beta and from the induction of apoptosis by the dietary agent sodium butyrate may be important in colorectal carcinogenesis. 828 10


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