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)

A case of carcinoma of the stomach associated with severe hypoglycemia is reported. Diagnosis of insulinoma was excluded on the basis of history as well as laboratory tests. Postmortem examination revealed widespread small metastases to various organs; no metastasis was found in the pancreas; the histology of this gland did not show any pathological finding. No impairment in pituitary, thyroid, adrenal and liver function was detected. Fasting blood sugar ranged from 18 to 56 mg/100 ml. An oral glucose tolerance test showed a diabetic pattern with low insulin. Tolbutamide, glucagon and glucose injected i.v. gave only a moderate rise in plasma insulin levels; plasma glucagon response to arginine was subnormal. The determination of NSILA-s and gastrin in the serum of this patient gave normal values. Diazoxide infusion induced an increase in blood glucose and subsequent treatment with diazoxide relieved hypoglycemia for some months. The occasional detection of an islet cell antibody by immunofluorescence in this case is not easily understandable, but it might partly account for the carbohydrate intolerance. An impairment in gluconeogenesis dependent upon some substrate deficiency might account for the hypoglycemia in this patient.
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PMID:Gastric carcinoma associated with severe hypoglycemia sensitive to diazoxide. 39 98

Transsphenoidal hypophysectomy was performed in 212 consecutive patients with metastatic breast cancer: 11 died within 30 days, two of surgical complications and nine of advanced metastatic disease. Two patients were unevaluable because of inadequate follow-up in one and simultaneous radiation treatment in the other. Of 199 evaluable patients 42% had an objective remission. Duration of remission averaged 18+ months with 10 out of 84 patients still in remission. Presence of estrogen receptors in the tumor significantly predicted response to hypophysectomy. Of 156 patients in whom completeness of hypophysectomy was assessed, 128 were thought to have a complete removal as shown by the fact that their growth hormone and prolactin were undetectable after stimulation with arginine or chlorpromazine, respectively. Of 26 patients in whom TRH test was performed, TSH and prolactin were undetectable in 20. Of 23 patients where autopsy was performed only six had microscopic pituitary tissue remaining. Hypophysectomy induced remission in eight of 15 patients who had previously responded and then relapsed to the antiestrogen Tamoxifen and in four of 17 who had failed. Conversely, antiestrogen therapy induced remission in six of 26 patients who had previously responded to hypophysectomy and in whom serum estrogens were present in small amount. These data indicate that both gonadal and pituitary hormones play a role in the growth of some human breast cancers.
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PMID:Transsphenoidal hypophysectomy in breast cancer: evidence for an individual role of pituitary and gonadal hormones in supporting tumor growth. 50 1

Epithelial mucins have obtained increasing clinical relevance since they were found in the serum of cancer patients and were shown to be elevated in metastatic disease. We report here the characterization of the monoclonal antibody (MAb) 436 which recognises the protein core of the polymorphic epithelial mucin (PEM) of the human breast. MAb 436 was generated by immunizing Balb/c mice with membrane-enriched fractions prepared from metastatic lesions in the axillary lymph nodes. The antigenic determinant recognized by the MAb 436 is expressed on the surface of breast cancer cells and was measured by ELISA on all of 50 cytosol preparations of primary breast tumors. Immunohistochemistry showed 98% of primary and 100% of metastatic breast cancer lesions to be positive with the 436 antigenic determinant expressed both in the cytoplasm and at the plasma membrane level of the tumor cells. Moreover, the antigen was expressed in a homogeneous fashion (80-100% of the total number of tumor cells) in more than 60% of the tumors. Reactivity with normal tissues was rare and scattered and restricted to glandular structures particularly at the luminal border level except for the distal and collecting tubules of adult and fetal kidney, where a cytoplasmic 436 antigen distribution was observed. Other cancers proved positive but the reactivity was always variable and heterogeneous. The antigen recognized by MAb 436 appears in Western Blotting as a M(r) of more than 200,000 daltons protein resolved in two bands. Epitope mapping experiments using overlapping octapeptides in the repeat unit of the PEM identified in the RPAP (Arg-Pro-Ala-Pro) sequence the binding site of the 436 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of monoclonal antibody 436 recognizing the Arg-Pro-Ala-Pro sequence of the polymorphic epithelial mucin (PEM) protein core in breast carcinoma cells. 137 74

Proto-oncogenes (H-ras-1 and L-myc) and tumor-suppressor gene (p53) loci have been implicated in lung carcinogenesis. DNA restriction fragment length polymorphisms at these gene loci are being evaluated in a case-control study as markers predictive of risk for cancer or of prognosis when cancer is present. The cases and controls had a cigarette-smoking history of 40 or more pack years or other abnormalities in pulmonary function tests, their ages were closely matched (64 years for cases and 61 years for controls) and the ratio of Caucasians to African Americans was close to unity (cases, 0.95:1.00, controls, 1.00:0.88). The H-ras-1 gene contains an insertion deletion polymorphism. Inheritance of rare H-ras-1 alleles, defined by MspI digestion, confers a relative risk for lung cancer of 2.0 (95% confidence interval, 0.5-7.3) for Caucasians and 3.2 (0.9-11.6) for African Americans (74 cases, 67 controls). The L-myc gene sequence has a restriction site (EcoR1) polymorphism between the second and third exons. Inheritance of restriction site-present alleles was reported to confer poor prognosis (presence of lymph node metastases) in Japanese lung cancer patients. This hypothesis was tested in both case-control study subjects (56 cases, 55 controls) and additional surgical cases (40), but no evidence was found to support the hypothesis in the U.S. population. The p53 gene is a tumor-suppressor gene that can encode either a proline or an arginine in the 72nd residue. No associations was found between the minor allele (proline) and diagnosis of lung cancer (76 cases, 68 controls).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship of H-ras-1, L-myc, and p53 polymorphisms with lung cancer risk and prognosis. 148 64

The injection of B16F10 melanoma cells with recombinant human tumor necrosis factor alpha (TNF-alpha) into the tail vein of C57BL/6 mice resulted in 2- to 25-fold more metastatic foci in the lungs than the injection of tumor cells alone. Clearly, TNF-alpha significantly enhanced experimental tumor metastasis. Furthermore, it enhanced the metastasis of Lewis lung carcinoma cells. In contrast, a mutein of TNF-alpha, designated as F4236, having the cell-adhesive sequence (Tyr-Ile-Gly-Ser-Arg) at the N-terminus of the TNF molecule did not enhance metastasis, but rather exhibited similar antitumor activity to wild-type TNF-alpha in fibrosarcoma-bearing mice.
Clin Exp Metastasis 1992 Jul
PMID:A YIGSR-containing novel mutein without the detrimental effect of human TNF-alpha of enhancing experimental pulmonary metastasis. 161 34

Human melanoma represents one of the most metastatic cancers in man. The capacity of melanoma cells to invade a variety of tissues and extracellular matrices is, in part, due to their repertoire of adhesion receptors. To this end, human melanoma cells express multiple integrin cell adhesion receptors among these is the vitronectin receptor, alpha v beta 3. This adhesion receptor enables melanoma cells to attach to a wide variety of extracellular matrix components containing the sequence Arg-Gly-Asp. This review will focus on the biosynthetic, biochemical and biological properties of this receptor expressed on the surface of human melanoma cells.
Cancer Metastasis Rev 1991 May
PMID:Structure, function and biological properties of integrin alpha v beta 3 on human melanoma cells. 171 71

We report on the inhibition of wound implantation by TA3Ha mammary carcinoma cells by Arg-Gly-Asp containing proteins and peptides using a hepatic wedge resection model. Intravenously injected TA3Ha cells rarely form tumor in the liver of syngeneic mice, but after hepatic wedge resection, 45% (107/240) of the mice develop tumors in the hepatic wound. Hepatic wound implantation is significantly (P = 0.01) inhibited by pretreating the cells with whole mouse plasma, but not with fibrinogen-depleted plasma or serum. Tumor inhibition is also achieved by pretreatment of cells with fibrinogen (P = 0.05-0.0004), fibronectin (P = 0.007) and laminin, but not by albumin. The active domain appears to be the RGDS sequence since the deca- and tetrapeptides containing RGDS inhibit wound implantation (P less than 0.05). However, the tetrapeptide Arg-Gly-Glu-Ser has no such activity. None of these agents affects ascites tumor formation by the intraperitoneally injected cells, suggesting that anchorage independent growth of cells is not affected. We propose that proteins and peptides containing RGD occupy the binding sites and prevent the cells from interacting with cell adhesion proteins in healing wounds. Proteins and/or peptides containing RGD may be useful for preventing local recurrence in postsurgical cancer patients.
Clin Exp Metastasis 1992 Jan
PMID:Inhibition of tumor implantation at sites of trauma by Arg-Gly-Asp containing proteins and peptides. 173 46

Recent studies have revealed a role for platelets and the platelet-adhesive proteins, fibronectin and von Willebrand factor (vWF) in platelet-tumor cell interaction in vitro and metastasis in vivo. The present report documents the effect of thrombin treatment of platelets on this interaction in vitro and in vivo. In vitro, thrombin at 100-1,000 mU/ml maximally stimulated the adhesion of six different tumor cell lines from three different species two- to fivefold. As little as 1-10 mU/ml was effective. The effect of thrombin was specific (inhibitable by hirudin, dansyl-arginine N-(3-ethyl-1,5 pentanediyl) amide and unreactive with the inactive thrombin analogue N-P-tosyl-L-phenylchloromethylketone-thrombin and D-phenylalanyl-L-propyl-L-arginine chloromethylketone-thrombin (PPACK-thrombin), and required high-affinity thrombin receptors (competition with PPACK-thrombin but not with N-P-tosyl-L-lysine-chloromethyl-ketone-thrombin). Functionally active thrombin was required on the platelet surface. Binding of tumor cells to thrombin-activated platelets was inhibitable by agents known to interfere with the platelet GPIIb-GPIIIa integrin: monoclonal antibody 10E5, tetrapeptide RGDS and gamma chain fibrinogen decapeptide LGGAKQAGDV, as well as polyclonal antibodies against the platelet adhesive ligands, fibronectin and vWF. In vivo, thrombin at 250-500 mU per animal increased murine pulmonary metastases fourfold with CT26 colon carcinoma cells and 68-413-fold with B16 amelanotic melanoma cells. Thus, thrombin amplifies tumor-platelet adhesion in vitro two- to fivefold via occupancy of high-affinity platelet thrombin receptors, and modulation of GPIIb-GPIIIa adhesion via an RGD-dependent mechanism. In vivo, thrombin enhances tumor metastases 4-413-fold with two different tumor cell lines.
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PMID:Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo. 184 69

The authors report on the influence of plasminogen activators (PA) on implantation of TA3Ha mammary tumor cells in the healing hepatic wounds of syngeneic strain A mice. Intravenously injected TA3Ha cells, although they rarely metastasize to the liver, formed tumors in the hepatic wounds of a significant percent (42%, P less than 0.0001) of mice. The frequency of tumor formation declined as the interval between surgery and tumor cell inoculation was increased. Furthermore, preexposure of cells to fibrinogen, fibronectin, laminin, or peptides containing the arginine-glycine-aspartic acid-serine residues dramatically reduced the frequency of tumor formation in the hepatic wounds. These results indicate that TA3Ha cells interact with fibrinogen-related proteins in the wound to aid their attachment and growth. Because these proteins are susceptible to digestion by plasmin, PA were used in this study to examine whether administration of these drugs to the mice would modulate tumor formation in the liver wounds. Among the PA tested, human plasmin B-chain-streptokinase complex (B-SK) and recombinant tissue plasminogen activator (t-PA) inhibited tumor implantation in a dose-related manner. Administration of 900 units (U) of B-SK or 3300 U of t-PA per mouse reduced the frequency of tumor formation from 42% to 0% (P = 0.02) and 11% (P = 0.02), respectively. The B-SK was complexed with p-nitrophenyl-p-guanidinobenzoate; it did not activate the plasminogen or inhibit tumor formation in the hepatic wounds. Although urokinase activated the plasminogen, it did not inhibit tumor implantation in the hepatic wound. Heparin, an anticoagulant that prevents conversion of fibrinogen to fibrin without being fibrinolytic, had no influence on tumor formation in the hepatic wounds. The PA can generate plasmin that digests the cell attachment proteins in wounds and consequently inhibits tumor cell attachment.
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PMID:Inhibition of tumor implantation at sites of trauma by plasminogen activators. 191 15

The role of cellular adhesion in regional lymph node metastasis of solid tumors has been investigated. The data reviewed is based on studies in four different tumor models of human, rat and murine origin. An in vitro assay measuring tumor cell attachment to cryostat sections of normal peripheral lymph nodes, obtained from the species of tumor origin was used to compare the adhesion of tumor sublines with different metastatic potentials. A good correlation was found between tumor cell potential to metastasize to regional nodes and the adhesion to the sections in all models studied. The adhesion of all tumor lines could be blocked by Arg-Gly-Asp containing peptides while pretreatment of the cells with antibodies to integrins implicated beta 1 and beta 3 receptor complexes in the adhesion. Ligand binding assays provided indirect evidence that the preferential attachment of the metastatic tumor lines to the frozen sections was mediated via extracellular matrix proteins such as fibronectin, vitronectin and type IV collagen. As these basement membrane proteins have been localized to the outer surfaces of reticular fibers which are known to permeate the lymph node and trasverse the subcapsular sinus it is postulated that tumor cell attachment to these fibers may facilitate and possibly be required for tumor cell retention and growth in the invaded regional nodes.
Cancer Metastasis Rev 1991 May
PMID:Adhesion mechanisms in lymphatic metastasis. 191 72


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