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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant tumors are generally characterized by extensive local tissue invasion and destruction of ECM which may be due to increased constitutive expression and activity of secreted proteases. Moreover, a large number of diverse protease activities may be constitutively over-expressed in a simultaneous or co-ordinated fashion, thereby significantly increasing cellular invasive potential of the cells. To explore this relationship, we have measured steady-state levels of mRNA coding for urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), transin and tissue-specific inhibitor of metalloproteinases (TIMP); as well as gelatinolytic, caseinolytic and plasminogen activator activities secreted by SPI, a non-metastatic mouse mammary carcinoma cell line and 4 metastatic sublines derived from it. mRNA encoding metalloproteinase transin was increased 15- to 20-fold, while TIMP transcripts were decreased 3-fold in the metastatic sublines compared to parental SPI tumor cells. Metastatic sublines secreted higher levels of gelatinase (i.e., 92 kDa and 64 kDa) as well as proteases with caseinolytic activity (i.e., 115 kDa and 57 kDa) when compared with SPI cells. Moreover, these enzymes were identified as neutral metalloproteinases. Although the amount of uPA mRNA appeared to be the same in SPI and the metastatic sublines, the latter secreted 1.5-3 times more uPA activity into the culture supernatants. Metastatic competence in the SPI tumor model is therefore associated with increased secretion of several metalloproteinase activities and uPA, as well as decreased TIMP expression, consistent with a more invasive phenotype.
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PMID:Constitutive expression and secretion of proteases in non-metastatic SP1 mammary carcinoma cells and its metastatic sublines. 204

A 75-year old obese female was scheduled for mastectomy due to breast tumor. At the preoperative examinations, she had premature atrial contraction on electrocardiogram. But she had no clinical signs or symptoms regarding sick sinus syndrome. She was evaluated as ASA risk II and arranged for neuroleptanesthesia. During the operation, she developed severe bradycardia and asystole lasting for 7 seconds, which was not effectively controlled by atropine sulfate. Then cardiac rhythm resumed spontaneously and she recovered with no neurological deficits. On the postoperative examination of 24 hr-Holter ECG, she showed bradycardia and sinus arrest and she was diagnosed to have sick sinus syndrome.
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PMID:[A case of sinus arrest during a surgical operation]. 205 89

While waiting for open heart surgery, in 153 patients (104 male, 49 female, 22-76 years of age) without gastrointestinal symptoms and/or history esophago-gastro-duodenoscopy was performed. 124 patients suffered from coronary heart disease, 29 from valvular defect, aneurysm of the sinus of Valsalva or tumor of the heart. In 47.1% endoscopy revealed serious abnormal findings: in 16.3% gastric ulcer, in 20.9% erosive gastritis, duodenal ulcer and erosive duodenitis in 5.2%, respectively, 1 case of gastric carcinoma, 2 of large polyps and 3 of reflux esophagitis of higher degree (totally 3.9%). In patients with coronary artery disease, the relation of erosive and ulcerous gastric lesions as compared with those of duodenal origin was 4:1, in patients with other cardiac diseases it was 2:1, respectively (p less than 0.001). Compared with a normal population, the incidence of pathological gastric findings was 54-fold higher in our patients, and 1.7-fold concerning duodenal lesions, respectively (p less than 0.001). 51 patients on acetylsalicylic acid (160 mg/die) showed pathologic findings in 41.2%, and 96 patients without ulcer-inducing therapy in 51%. Thus, low-dose Aspirin does not seem to have serious gastric side effects. The results of the study stress the necessity of routinely performed endoscopy of the upper gastrointestinal tract in patients awaiting open heart surgery. This will lead to a lower incidence of serious gastrointestinal complications postoperatively which are known to have a high mortality.
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PMID:[Frequency of pathological changes of the upper gastrointestinal tract in patients awaiting heart surgery]. 208 20

Extracellular matrix metalloproteases are secreted by the resident cells of the tissue in a proenzyme form, and their extracellular activity is regulated at the level of gene expression, proenzyme activation, and interaction with inhibitors. To understand the molecular mechanisms that control the activity of ECM metalloproteases and their effect on the cellular phenotype, we have established cell lines in which the transcription of the protease genes is repressed. We also have undertaken a detailed study of the pathway of extracellular activation of interstitial procollagenase. Stable transfection of three human tumor cell lines--H-ras-transformed bronchial epithelial cells TBE-1, fibrosarcoma cells HT1080, and melanoma cells A2058--with the adenovirus E1A gene dramatically repressed the expression of the secreted proteases, type IV and interstitial collagenases, and urokinase-type plasminogen activator. Concomitantly, E1A-expressing cells showed reduced metastatic activity in vivo and reduced ability to traverse a reconstituted basement membrane in vitro. Monospecific anti-type IV collagenase antibody inhibited the invasive activity of parental tumor cell lines in the in vitro system, suggesting a possible causal relationship between the effect of E1A on the expression of secreted proteases and the reduced metastatic potential of the E1A-expressing transformants. We have also studied the mechanism of regulation of metalloprotease activity at the level of extracellular activation by investigating the cascade of proteolytic events that results in the activation of interstitial procollagenase. Cocultivation of the major cellular components of skin, dermal fibroblasts, and epidermal keratinocytes induces activation of interstitial procollagenase and prostromelysin in the presence of plasminogen. This activation occurs through a uPA-plasmin-dependent pathway in which plasmin catalyzes the first step in activation of both collagenase and stromelysin by amino-terminal processing. Activated stromelysin can in turn convert plasmin-activated collagenase into a fully active enzyme by removal of approximately 15 amino acid residues from the carboxyl end of the enzyme. This second step of activation results in a 5-8-fold further increase in specific activity of collagenase. This cascade of proteolytic events may constitute a major physiologic pathway of collagenase activation.
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PMID:Secreted proteases. Regulation of their activity and their possible role in metastasis. 215 52

TGF-beta stimulates the anchorage-dependent proliferation of some cells and inhibits the proliferation of others. Although the ability of TGF-beta to affect different cell types in opposite ways is puzzling, it may not reflect fundamental differences in the initial cellular responses to TGF-beta. Instead, the different types of cellular responses may be because TGF-beta initiates a number of changes in all responsive cells, some of which may lead to proliferation and others, to proliferative arrest. Depending on the individual responses of specific cell types and on the environment of the cells, the balance of the effects of these changes could lead to cellular proliferation or inhibition of proliferation. This hypothesis is discussed in more detail below, with specific reference to the effects of TGF-beta on the expression of genes encoding proteases, protease inhibitors, ECM components, and growth and differentiation factors. TGF-beta also promotes the anchorage-independent growth of some cells in soft agar, but inhibits the anchorage-independent proliferation of some tumor cells. In stimulating proliferation TGF-beta often acts synergistically with EGF, FGF, TGF-alpha, or PDGF. The observed increase in soft agar growth in response to TGF-beta could be explained by a model which proposes that TGF-beta stimulates the accumulation of the ECM, which supports the action of the growth factors (e.g., EGF, TGF-alpha, PDGF, and FGF) that directly stimulate cellular proliferation. The ability of TGF-beta to inhibit the proliferation of some cells in soft agar again reminds us that the mechanism of action of this growth factor is not readily described by a single model. Although its proven ability to regulate the expression of genes that encode proteins that constitute or modify the ECM ensures TGF-beta a role in ECM remodeling, the complexity of the multiple cellular responses to this growth factor suggest that there is another aspect of the function of this growth factor. Perhaps the observations that TGF-beta stimulates the production of FSH and PDGF are the tip of the iceberg. If TGF-beta regulates a subset of genes that encode growth factors and their receptors, then this could help to explain the many and varied cellular responses to TGF-beta. By regulating genes encoding other hormones and growth factors, TGF-beta might be a "master morphogen" during development and orchestrate the local elaboration of growth factors and hormones by individual cell types.
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PMID:Transforming growth factor-beta and its actions on cellular growth and differentiation. 216 98

In neurosurgical operation, when the focus is close to the central fissure, precise delineation of the precentral motor and postcentral somatosensory areas is cardinal in defining the extent of the surgical resection. Eight ASA II-III patients scheduled for neurosurgery for intractable complex partial seizure (n = 5) and intracranial tumor (n = 3) were enrolled in the study. Subdural grids of electrodes were used for recording cortical evoked somatosensory potentials elicited by stimulating the median nerves to locate the primary somatosensory cortex and to delineate the central fissure through demonstration of phase-reversal pattern across the rolandic fissure. In all cases under general anesthesia, we were able to determine precisely the location of the central fissure. At the same time, we detected the evoked potential from SII (second sensory area) in one patient with intracerebral tumor. In conclusion, Co-SEP under general anesthesia is feasible and recommended to be performed as a routine intraoperatively for intractable epilepsy and tumor originating close to the primary motor or sensory strip in order to avoid iatrogenic damage to the vital cerebral cortex.
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PMID:Demarcation and localization of primary sensor and motor areas in human cortex by cortical somatosensory. Evoked potential (Co-SEP) during operation in surgery for epilepsy and intracranial tumor. 227 68

The effects of prostaglandin synthesis inhibitors on development of N-nitrosobis(2-oxopropyl)amine (BOP)-initiated pancreatic tumors were investigated. Female Syrian golden hamsters were given five weekly s.c. injections of BOP (10 mg/kg body weight) during the first 5 weeks and then given 20 p.p.m. indomethacin in the drinking water, 0.25% phenylbutazone in the diet, 1% aspirin in the diet, or no treatment (control group). The resultant incidence of pancreatic carcinoma at week 32 was significantly lower (P less than 0.05) in animals receiving phenylbutazone (36.8%) than in the controls (71.4%) and the numbers of carcinomas per hamster were significantly reduced by indomethacin (0.63) and phenylbutazone (0.58) treatment compared with the control group value (1.29). Aspirin also showed a tendency to decrease pancreatic tumor incidence, but this was not significant. Thus, prostaglandin synthesis inhibitors reduce the development of pancreatic cancer when administered during the post-initiation phase in this animal model.
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PMID:Effects of various prostaglandin synthesis inhibitors on pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine. 231 Nov 81

The capacity of various blood-borne cells, whether normal or malignant, to extravasate was found to correlate with heparanase-mediated degradation of HS in subendothelial ECM. This degradation was stimulated by proteases or plasminogen and inhibited by native heparin and by various modified nonanticoagulant species of heparin. These heparins also induced a marked reduction in tumor cell metastasis and autoimmune diseases in experimental animals. Heparanase-mediated degradation of HS in ECM also released EC growth factors that are stored in ECM, most likely by high affinity binding to HS. Such growth factors were extracted from subendothelial ECM synthesized in vitro and from basement membranes of the cornea in vivo, and are structurally and functionally related to bFGF;bFGF binds to ECM and is readily released by incubation with either HS, heparin or low MW heparin fragments as well as by various normal and malignant cells and by heparanase-mediated degradation of ECM HS. In contrast, there was little or no release of growth-promoting activity upon incubation of ECM with hyaluronic acid, chondroitin sulfate or chondroitinase ABC. A model is proposed suggesting that regulation of capillary growth and neovascular response may result from displacement of an angiogenic protein (bFGF) from its storage sites within basement membranes.
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PMID:Involvement of heparanase in tumor metastasis and angiogenesis. 246 49

N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide (FANFT), a potent urinary bladder carcinogen, is metabolically activated in vitro by a variety of enzyme systems including aerobic cooxidation by prostaglandin H synthase which is present in the rat bladder mucosa. In a previous experiment, aspirin coadministered with FANFT for 12 weeks inhibited FANFT-induced bladder carcinogenesis and enhanced forestomach carcinogenesis. To further evaluate the effects of aspirin on FANFT carcinogenesis, male F344 rats were fed either FANFT (0.2% of the diet) for 12 weeks (Group 4), aspirin (0.5% of the diet) simultaneously with FANFT for 12 weeks (Group 2), aspirin simultaneously with FANFT for 12 weeks and then subsequently to the end of the experiment (Group 1), or FANFT only followed by aspirin (Group 3). The incidence of bladder carcinoma was significantly higher when aspirin was fed after FANFT treatment (87%) compared to FANFT followed by control diet (48%) and was higher in rats given aspirin plus FANFT followed by aspirin (73%) compared to aspirin plus FANFT followed by control diet (47%). Aspirin alone given for 13 weeks (Group 6) or throughout the experiment (68 weeks) (Group 5) did not induce bladder cancer. However, in all groups administered aspirin long-term, renal papillary necrosis and renal pelvic hyperplasia and atypia were frequently observed. Only a single forestomach tumor was observed. In the present experiment, aspirin appeared to exhibit promoting activity for bladder carcinogenesis in the rat.
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PMID:Effect of aspirin on urinary bladder carcinogenesis initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide in rats. 249 54

Blood platelets are thought to be involved in certain aspects of malignant dissemination. To study the role of platelets in tumor cell adherence to vascular endothelium we performed studies under static and flow conditions, measuring tumor cell adhesion in the absence or presence of platelets. We used highly metastatic human adenocarcinoma cells of the lung, cultured human umbilical vein endothelial cells (ECs) and extracellular matrices (ECM) prepared from confluent EC monolayers. Our results indicated that under static conditions platelets do not significantly increase tumor cell adhesion to either intact ECs or to exposed ECM. Conversely, the studies performed under flow conditions using the flat chamber perfusion system indicated that the presence of 2 x 10(5) pl/microliters in the perfusate significantly increased the number of tumor cells adhered to ECM, and that this effect was shear rate dependent. The maximal values of tumor cell adhesion were obtained, in presence of platelets, at a shear rate of 1,300 sec-1. Furthermore, our results with ASA-treated platelets suggest that the role of platelets in enhancing tumor cell adhesion to ECM is independent of the activation of the platelet cyclooxygenase pathway.
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PMID:Platelet and shear rate promote tumor cell adhesion to human endothelial extracellular matrix--absence of a role for platelet cyclooxygenase. 250 57


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