Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Understanding the molecular mechanisms of invasion and metastasis is crucial for the development of novel therapeutic strategies to treat metastases. Considerable studies revealed that the establishment of metastasis is the final outcome of a series of processes such as tumor growth, angiogenesis, tumor cell detachment and invasion of extracellular matrix. Each step of this multistep process is essential for tumor cell survival and establishment of secondary lesions and is regulated by interactions of tumor cells with host microenvironment. This review is focused on the molecular mechanisms involved in the regulation of this processes. The central role of adhesion molecules and ECM degrading proteinases in disruption of cell-cell and cell-ECM associations as well as degradation of extracellular matrix and basement membranes is emphasized.
 ...
PMID:Invasion and metastasis in pancreatic cancer. 1043 84

The ECM of astrocytic tumors promotes and modulates a variety of cell functions, such as cell attachment, migration, proliferation, survival, and signaling. Recent studies indicate that there are extensive and complex interactions among ECM molecules and that these can modify the function of the participating molecules, interactions between the proteoglycan, phosphacan, and the ECM protein, tenascin, being an example (63). In addition, on nonastrocytic cell types it has been shown that an integrin receptor and the cell surface proteoglycan CD44 recognize the same ECM ligand osteopontin, and thus modulate each others function (77, 86). Thus, interacting components in the ECM and cell surface receptors likely cooperate in regulating cell function and tumor invasion (59, 77, 80, 85-87, 95). As tumor cells are capable of remodeling their ECM through synthesis of ECM proteins and proteoglycans, as well as upregulating integrin receptors and proteoglycans on their cell surface, tumor cells are capable of controlling their own destiny. ECM molecules which are concentrated in blood vessels of malignant astrocytomas, such as tenascin-C and the 250-kDa CSPG (NG2), are potentially therapeutic targets.
 ...
PMID:The extracellular matrix of gliomas: modulation of cell function. 1051 26

Tissue factor (TF), the cell-surface receptor for coagulation factor VIIa, supports metastasis. Equally important for this process are (a) interactions of the TF cytoplasmic domain, which binds the mobility-enhancing actin-binding protein 280, and (b) the formation of a proteolytically active TF-VIIa complex on the tumor cell surface. In primary bladder carcinoma cells, we find that this complex localizes to the invasive edge, in proximity to tumor-infiltrating vessels that stain intensely for TF pathway inhibitor (TFPI-1), the major inhibitor of the protease activity of the complex. In culture, binding of VIIa to TF-expressing tumor cells is sufficient to allow cell adhesion, migration, and intracellular signaling on immobilized TFPI-1. Immobilized heparin, a mimic for extracellular matrix-associated proteoglycans, binds physiological concentrations of TFPI-1 in a conformation that supports TF-VIIa-dependent cell adhesion. Consistent with a functional role of TFPI-1 in complex extracellular matrices, we show that TF cooperates with integrin-mediated adhesion and migration on composite matrices that contain ligands for both integrins and the TF-VIIa complex. This study thus provides evidence for a novel mechanism of protease-supported migration that is independent of proteolytic matrix degradation but rather involves protease-dependent bridging of TF's extracellular domain to an ECM-associated inhibitor.
 ...
PMID:Tumor cell adhesion and migration supported by interaction of a receptor-protease complex with its inhibitor. 1054 20

The aim of the study was to assess the differential intra- and intertumoral heterogeneity and patterns of matrix metalloproteinase expression in human glioblastomas in vivo. 12 glioblastoma samples were analyzed for MMP expression by semi-quantitative RT-PCR. A total of 56 samples (8 adjoining regions of 6 glioblastoma tumors) were immunohistochemically examined for the expression and regional distribution of gelatinase-A (MMP-2), gelatinase-B (MMP-9), matrilysin (MMP-7) and stromelysin-1 (MMP-3). Gelatinase-A mRNA was detected in all samples, gelatinase-B was found in numerous samples. Correspondingly, strong expression levels of both gelatinase protein was seen in immunohistochemistry. Gelatinase-A was expressed by both tumor cells and endothelium while gelatinase-B was found to be restricted to endothelial cells. Stromelysin-1 protein was not detected in any of the samples. Matrilysin was found around tumor cells of three samples from one patient only. The strong immunoreactivity seen for gelatinase-A around tumor cells and blood vessels suggests a role in both tissue degradation and tumor neoangiogenesis which is in accordance with previously published in vitro data. The marked localization of gelatinase-B to the endothelium and its presence in non-infiltrative benign lesions, however, makes a direct proteolytic role of gelatinase-B on ECM components during glioma invasion appear unlikely. Its close association with vascular structures, however, might indicate a link to neoangiogenesis. The significance of matrilysin which was only seen in tumor cells in three samples remains unclear. Stromelysin-1, though strongly expressed in cell lines, does not appear to play a role in glioblastoma tumors in vivo.
 ...
PMID:Heterogeneous regional expression patterns of matrix metalloproteinases in human malignant gliomas. 1057 6

The purpose of this work was to analyze the literature published in English and to review the experience of the Barrow Neurological Institute (BNI) with spine and spinal cord injury (SCI) in children. Standard computerized data bases were queried for information regarding SCI, spinal injury, spinal instability, and spinal cord regeneration to produce a review of the epidemiology, diagnosis, treatment, outcome and directions for future research. We also reviewed our experiences in the management of infants and children with spine injuries and SCIs and with spinal instability from all causes. A total of 132 articles were identified and obtained from the Medical Library at St. Joseph's Hospital and Medical Center in Phoenix, Ariz. and through interlibrary loan. All these articles were read, although not all were used in the final review. A review of all children with SCIs revealed that fractures treated over the past 20 years at the BNI were very rare in preadolescent children, who suffered mostly from ligamentous injury or SCI without radiographic abnormality. A total of 68 children aged 16 years or younger who had been treated over the past 15 years and who had undergone spinal fusions for trauma, congenital anomalies, or tumor resection were identified. Occipitocervical fusion is well tolerated in children as young as 11 months when internal stabilization with a threaded titanium rod is used. Posterior instrumentation, including pedicle screw fixation, is feasible in children as young as 4 years. Fusion techniques derived from the adult spinal instrumentation experience were found appropriate except for the youngest patients. Fusion in the newborn period was futile in our experience. The adolescent spine does not differ from the adult spine in terms of sensitivity or response to fixation. Children past the neonatal period can be successfully instrumented for spinal stability without apparent long-term sequelae. Related advances are needed in the area of prevention. Long-term advances in spinal cord regeneration can be expected from ongoing basic science investigations.
 ...
PMID:Pediatric spine and spinal cord trauma. State of the art for the third millennium. 1060 16

Using naturally serum-free SU-ECM basement membranes as invasion substrates showed that plasma fibronectin was necessary to stimulate invasion by DU 145 human and metastatic MATLyLu (MLL) rat prostate carcinoma cells. This activity mapped to the PHSRN sequence, which induced invasion through alpha5beta1 integrin. PHSCN, a competitive inhibitor, blocked both PHSRN- and serum-induced invasion. Acetylated, amidated PHSCN (Ac-PHSCN-NH2) was 30-fold more potent; however, Ac-HSPNC-NH2 was inactive. Rats receiving injections s.c. with 100,000 MLL cells were treated systemically by i.v. injection three times weekly with 1 mg of either Ac-PHSCN-NH2 or Ac-HSPNC-NH2 beginning 24 h later, three times weekly with 1 mg of Ac-PHSCN-NH2 beginning only after surgery to remove large (2 cm) MLL tumors, or were left untreated. MLL tumors grew rapidly in Ac-HSPNC-NH2-treated and in untreated rats. MLL tumor growth in rats treated with Ac-PHSCN-NH2 beginning 1 day after MLL cell injection was reduced by 99.9% during the first 16 days of treatment, although subsequent tumor growth occurred. MLL tumor cryosections immunostained with anti-PECAM-1 showed that Ac-PHSCN-NH2 inhibited neovascularization by 12-fold during this time. Whether initiated after MLL cell injection or only after MLL tumor removal, Ac-PHSCN-NH2 treatment reduced the numbers of MLL lung colonies and micrometastases by 40- to >100-fold, whereas Ac-HSPNC-NH2 was inactive. Thus, Ac-PHSCN-NH2 may be a potent antitumorigenic and antimetastatic agent for postsurgical use prior to extensive metastasis.
 ...
PMID:Anti-invasive, antitumorigenic, and antimetastatic activities of the PHSCN sequence in prostate carcinoma. 1066 82

Cyclooxygenase (COX)-2 levels are elevated in several types of human cancer tissues. Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both the COX-1 and COX-2 protein, the two enzymes that convert arachidonic acids to prostaglandins. Regular use of such NSAIDs significantly reduces the risk and spread of some cancers. The objective of this study was to elucidate the molecular pathology of neoplasms that overexpress COX-2. Epidemiological data and clinical studies were analyzed and compared with results of studies of human tumor tissues, animal models, and cultured tumor cells. COX-2, but not COX-1, is highly expressed in human colon carcinoma, squamous cell carcinoma of the esophagus, and skin cancer. COX-2 is inducible by oncogenes ras and scr, interleukin-1, hypoxia, benzo[a]pyrene, ultraviolet light, epidermal growth factor, transforming growth factor beta, and tumor necrosis factor alpha. Dexamethasone, antioxidants, and tumor-suppressor protein p53 suppress COX-2 expression. COX-2 synthesizes prostaglandin E2 (PGE2) which stimulates bcl-2 and inhibits apoptosis, and induces interleukin-6 (IL-6) which enhances haptoglobin synthesis. PGE2 is associated with tumor metastases, IL-6 with cancer cell invasion, and haptoglobin with implantation and angiogenesis. Drastic reduction in polyp number results from COX-2 gene knockout as well as from selective COX-2 inhibition in a mouse model of human familial adenomatous polyposis. Nonselective NSAIDs, for instance aspirin, and selective COX-2 inhibitors such as celecoxib (SC-58635) and NS-398 suppress azoxymethane-induced colon carcinogenesis in rats. Aspirin, indomethacin, and ibuprofen decrease cultured lung cancer cell proliferation. Selective inhibition of COX-2 is preferable to nonselective inhibition. It reduces cancer cell proliferation, induces cancer cell apoptosis, and spares COX-1-induced cytoprotection of the gastrointestinal tract.
 ...
PMID:Molecular pathology of cyclooxygenase-2 in neoplasia. 1067 79

The intriguing problem of metastasis requires the spreading of metastatic cells through the basement membrane barrier. The interaction of the basement membrane with the metastatic cell is a cell surface activity involving the function of integrin receptors. Integrins are a group of alpha,beta heterodimeric proteins responsible for transducing intracellular signals on binding to the extracellular matrix proteins present in the basement membrane. To understand the role of integrin receptors in tumor metastasis, the cell surface receptor functions were modulated by All Trans Retinoic Acid (ATRA) treatment in B16F10 tumor cells. Our experimental results clearly indicate that All Trans Retinoic Acid (ATRA) inhibit metastatic potential of highly metastatic B16F10 melanoma cells by 1) downregulating the cell surface integrin receptors against ECM proteins specially laminin and vitronectin and 2) by inhibiting the 72 kd collagenase activity.
 ...
PMID:Effect of retinoic acid on integrin receptors of B16F10 melanoma cells. 1084 Sep 41

Non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin have been shown to suppress colon carcinogenesis and in some cases reduce the size of colorectal polyps. Balsalazide disodium (BSZ) is a colon-specific prodrug of the salicylate, 5-aminosalicylic acid. The aim of the present study was to test the chemopreventive activity of BSZ in two established animal models of colon tumorigenesis, azoxymethane-induced aberrant crypt formation in the rat and intestinal tumor formation in the B6-Min/+ mouse. Aberrant crypt foci (ACF) were induced in Fischer 344 rats via 2 subcutaneous injections of azoxymethane (20 mg/kg). BSZ was supplied in the drinking water for 8 weeks and ACF quantitated. B6-Min/+ mice were treated from 55 days of age for 90 days and intestinal tumors scored for number, size and location. BSZ treatment of AOM-injected rats reduced ACF formation in a dose-dependent manner by 60% with the greatest effect observed on ACF with 4 or more crypts. In B6-Min/+ mice a dose-dependent reduction of intestinal tumor number was observed which reached 80% in the distal small intestine and colon. A preliminary mechanistic study in cultured human colon cancer cells showed that both BSZ and 5-ASA inhibited colon cancer cell proliferation in vitro. However, 5-ASA but not BSZ produced changes consistent with the induction of apoptosis. BSZ produces a dose-dependent chemopreventive effect on colon carcinogenesis. A possible mechanism is consistent with the inhibition of cellular proliferation and the induction of apoptosis.
 ...
PMID:Chemoprevention of colon cancer carcinogenesis by balsalazide: inhibition of azoxymethane-induced aberrant crypt formation in the rat colon and intestinal tumor formation in the B6-Min/+ mouse. 1085 36

Epidemiologic and animal studies indicate that sustained use of non-steroidal anti-inflammatory drugs (NSAIDs) have a chemopreventive effect against the incidence of colorectal neoplasia and subsequent mortality. We previously demonstrated that sulindac significantly reduces intestinal tumor load in Apc(Min/+)mice and the tumor regression was not necessarily correlated with prostaglandin biosynthesis. In the present study, we further investigate the relationship of NSAID treatment and tumorigenesis in the Apc(Min/+)mouse model. We demonstrate that indomethacin (9 ppm) is a very potent chemopreventive agent, reducing tumor load by 85% and significantly inhibiting basal and ex vivo prostaglandin formation (P< 0.006 and P< 0.0001, respectively). Aspirin (400 ppm) has a similar impact on reducing prostaglandin levels, but in contrast to indomethacin, is uneffective in reducing the tumor load. The data indicate a discordance between the impact of different NSAIDs on tumorigenesis in Apc(Min/+)mice.
 ...
PMID:Discordant effect of aspirin and indomethacin on intestinal tumor burden in Apc(Min/+)mice. 1088 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>