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)

Tumor cell invasion and metastasis is highly dependent on dynamic changes in the adhesion and migration of transformed and malignant cells. As with normal cell adhesion, the adhesion of tumor cells influences their cytoskeletal organization, activation of signal transduction pathways within the cell, and nuclear events leading to changes in mRNA transcription and protein synthesis. Furthermore, as tumor cells invade the circulation, they adhere to activated endothelial cells at sites within the vasculature during arrest and extravasation. Studies in the area of tumor cell adhesion and migration have demonstrated that the recognition of extracellular matrix ligands, or adhesion promoting ligands expressed on neighboring cells (i.e. counter-receptors), involves complex molecular recognition mechanisms. The complexity arises, in part, from the multiple recognition sites that are present within adhesion promoting ligands. Some of these structures within ECM components act by binding integrins, whereas others bind additional receptors such as cell surface proteoglycans. In this sense, adhesion promoting ligands may be considered as informational arrays, that function to modulate cell phenotype by engaging specific combinations of adhesion receptors on the cell surface. Understanding the mechanism(s) by which these receptor 'cluster' modify cell adhesion, motility and growth may lead to novel therapeutic strategies to control tumor cell invasion and metastasis formation. This review will highlight the role that cell surface chondroitin sulfate proteoglycans may play in modulating tumor cell adhesion, migration and invasion, with an emphasis on the relationship between cell surface chondroitin sulfate proteoglycans and integrins.
 ...
PMID:Cell surface chondroitin sulfate proteoglycans in tumor cell adhesion, motility and invasion. 877 1

An induction of laminin in the confrontation zone between tumor cells and normal brain tissue has been observed in our model systems in vivo and in vitro. In order to study the effects of ECM components on glioma-cell migration and invasion, we have used 2 lacZ-transfected glioma cell lines, AN1/lacZ and U-251 /lacZ. Cell migration from multicellular spheroids was studied using different types of media: DMEM with 10% serum, Ultra Culture medium, and filtrated DMEM with serum in which the protein fraction > 100 kDa had been removed by ultrafiltration. Laminin, fibronectin and collagen type-IV were individually added to the different media, and cell migration from the spheroids was studied. The results show that cell migration in both cell lines, was stimulated by laminin and fibronectin. Collagen type-IV stimulated only cell migration of U-251/lacZ cells. Scanning electron microscopy revealed an extensive change in cell shape as a result of laminin stimulation. Flowcytometric studies showed that both AN1/lacZ and U-251/lacZ strongly express the alpha3 beta1 integrin receptor, which can bind to several ECM components (laminin, fibronectin, collagen). Immunofluorescence microscopy demonstrated that the same integrin sub-units were expressed in multicellular spheroids. When monoclonal antibodies to alpha3 and beta1 were added to the laminin-stimulated cultures, cell migration was significantly reduced. This indicates that the alpha3 beta1 integrin receptor plays an important role during glioma-cell migration.
 ...
PMID:Stimulation of glioma-cell migration by laminin and inhibition by anti-alpha3 and anti-beta1 integrin antibodies. 882 48

CD44 cell adhesion molecule (PgP-1, ECM III, Hermes antigen) is a polymorphic integral membrane glycoprotein associated with cell matrix adhesion, lymphocyte activation, recirculation, and homing. CD44 expression has been reported in in malignant lymphoma and in a variety of epithelial human cancers but has not been studied as a prognostic marker in urinary bladder transitional cell carcinoma. CD44s (standard 85- to 95-kDa macromolecule) expression was measured by qualitative and image analysis-quantitated immunohistochemical techniques using the A3D8 monoclonal antibody. CD44v6 (a splice variant exon of CD44s) expression was measured by qualitative immunohistochemical techniques using the 2F10 monoclonal antibody. The results of CD44s and CD44v6 expression were compared with tumor grade, pathologic stage, and DNA content analysis on Feulgen-stained tissue sections in 44 cases of urinary bladder transitional cell carcinoma. The mean percentage-positive area of staining intensity for CD44s expression in Grade 1 tumors was 61%, compared with 30% for the Grade 3 tumors (P < 0.001). Non-invasive tumors featured a 59%-positive area of staining intensity, compared with the 30% staining percentage for the deeply invasive tumors (P < 0.001). There was significant correlation of aneuploid DNA content with loss of CD44s staining (P < 0.05). The staining results for CD44v6 paralleled those for the CD44s, with a significant loss of staining in high-grade and high-stage aggressive tumors in comparison with the low-grade nonaggressive tumors (P < 0.01). In urinary bladder transitional cell carcinoma, CD44s and CD44v6 expression parallels that for other cell adhesion molecules, such as E-cadherin, that feature a significant progressive loss of immunoreactivity in association with tumor dedifferentiation, advancing pathologic stage, and abnormal DNA content.
 ...
PMID:Expression of the CD44 cell adhesion molecule in urinary bladder transitional cell carcinoma. 887 28

Tissue inhibitor of metalloproteinases (TIMP) 1, 2 and 3 are related proteins that can form complexes with all known matrix metalloproteinases (MMPs). They inhibit the action of MMPs on extracellular matrix components. The balance of MMPs and TIMPs is important for tissue remodeling and its disturbance is believed to play a crucial role in pathophysiological processes such as tumor metastasis, destruction of cartilage and fibrosis. Cytokines and growth factors were found to regulate TIMPs and MMPs in a complex manner. In order to better understand the role of TIMPs in inflammatory joint diseases we have studied in vitro the regulation of TIMP-1 and TIMP-3 by inflammatory cytokines in cultured human synovial lining cells. We found that transforming growth factor beta 1 as well as interleukin-1 beta induce gene expression of both TIMP-1 and TIMP-3. In contrast, oncostatin M, an interleukin-6-type cytokine produced by activated T-lymphocytes and monocytes, had a differential effect on TIMP mRNA levels. After oncostatin M treatment, TIMP-1 expression was up-regulated but basal, as well as interleukin-1 beta-induced, TIMP-3 expression was inhibited. Interleukin-6 itself had no effect on synovial lining cells but a complex of interleukin-6 and the soluble interleukin-6 receptor induced activation of signal transducer and activator of transcription (STAT) factors in these cells and regulated TIMP-1 and TIMP-3 expression in a similar fashion as oncostatin M. Since TIMP-3 is matrix-associated whereas TIMP-1 is found in many body fluids, the role of oncostatin M during inflammatory processes might be to promote ECM degradation in the local environment but to prevent it systemically.
 ...
PMID:Oncostatin M differentially regulates tissue inhibitors of metalloproteinases TIMP-1 and TIMP-3 gene expression in human synovial lining cells. 889 88

MDR1 P-glycoprotein in membranes of human tumor cells of the CEM/VBL100 line was selectively labelled using photoreactive analogs of verapamil, N-(p-azido-3-[125I]salicyl)amino-verapamil ([125I]ASA-V) and prazosin, 2-[4-(4-azido-3-[125I]iodobenzoyl)piperazin-1-yl]4 -amino-6,7-dimethoxyyquinazoline ([125I]ASA-P). Mefloquine, a quinolinemethanol antimalarial drug, was shown to inhibit the labelling of P-glycoprotein with an efficiency similar to that for verapamil, a known chemosensitizer. By contrast, chloroquine competed poorly for the binding site on P-glycoprotein. Mefloquine also inhibited the functional activity of P-glycoprotein. It decreased the rates of extrusion of [3H]vinblastine and the fluorescent dyes, fluo-3 acetomethoxy ester and rhodamine 123, from drug-resistant cells and decreased the level of resistance of these cells to vinblastine. The ability of mefloquine to inhibit P-glycoprotein function may be involved in the neurotoxic side-effects occasionally associated with the use of mefloquine as an antimalarial drug.
 ...
PMID:Modulation of the function of human MDR1 P-glycoprotein by the antimalarial drug mefloquine. 893 69

The role of protein phosphatase-2A (PP-2A) in regulating the motility and adhesion of human head and neck squamous cell carcinomas (HNSCC) was investigated. Immunofluorescent staining of these HNSCC cells showed PP-2A can co-localize with microtubules. That the PP-2A influences motility was shown by the increase in HNSCC cell migration through laminin and vitronectin when PP-2A was selectively inhibited with low dose okadaic acid, and by the reduction in invasion through these same matrix components by elevators of PP-2A activity. Motility of HNSCC cells through collagen I or fibronectin was not modulated by PP-2A. The reduction in HNSCC migration through vitronectin or laminin that resulted from treatment with PP-2A elevators was associated with an increase in cellular adhesiveness to these same ECM components. These studies show the association of PP-2A with the cellular cytoskeleton and its role in restricting the invasiveness of tumor cells through select extracellular matrix components.
 ...
PMID:Protein phosphatase-2A association with microtubules and its role in restricting the invasiveness of human head and neck squamous cell carcinoma cells. 902 32

PCR assays for the presence of mutant K-ras or p53 sequences are potentially useful as sensitive tests for tumor diagnosis. The technical challenge is to design assays sensitive enough to detect a few molecules of mutant DNA yet sufficiently specific that a false positive signal is not produced by a 10(5)- or 10(6)-fold excess of normal DNA. We determined the detection limit of allele-specific PCR (ASA) as a function of the particular mismatch involved using all 12 possible mismatches in two different DNA sequence contexts (K-ras codon 12 and p53 codon 273). Depending on the identity of the mismatch, mismatched template was amplified 10(2)-10(4)-fold less than perfectly matched template. In other words, a mutant allele could be detected by ASA if it represented > 1-0.01% of the total DNA from that locus. Peptide nucleic acid (PNA) clamping was used to improve the K-ras ASA assay. Selective amplification of mutant sequences was achieved using a PNA complementary to the normal sequence to inhibit the amplification of wild-type DNA. PNA clamping followed by ASA resulted in significant improvement in sensitivity and specificity, permitting the detection of tumor DNA diluted with a 300,000-fold excess of normal human DNA.
 ...
PMID:Analysis of the allele-specific PCR method for the detection of neoplastic disease. 902 37

Tissue organization and maintenance within multicellular organisms is in part dependent on the ability of cells to undergo programmed cell death or apoptosis. Conversely, disruption of cell death pathways often is associated with tumor development. At present, the molecular control of apoptosis in epithelial cells is poorly understood. Here we describe evidence linking epidermal growth factor-receptor (EGF-R) activation to survival of normal human keratinocytes in culture. Inhibition of EGF-R activation by an anti-EGF-R antagonistic monoclonal antibody (mAb 425), followed by detachment of keratinocytes from the substratum, induced extensive death with several features of apoptosis in keratinocyte cultures. Other, non-epithelial normal human cells including melanocytes and fibroblasts, did not show this effect. Similar to EGF-R blockade by mAb 425, inhibition of the EGF-R tyrosine kinase activity using tyrphostin AG1478 resulted in lack of attachment and extensive cell death upon passaging. Attachment to keratinocyte-derived ECM partially resuced mAb 425-treated keratinocytes from cell death, indicating that adhesion-dependent and EGF-R-dependent signal transduction pathways serve partially overlapping but not redundant roles in supporting keratinocyte survival.
 ...
PMID:EGF-R dependent regulation of keratinocyte survival. 904 42

Aspirin, along with its analgesic-antipyretic uses, is now also being considered for prevention of cardiovascular disease, cancer, and treatment of human immunodeficiency virus infection. Although many of aspirin's pharmacological actions are related to its ability to inhibit prostaglandin biosynthesis, some of its beneficial therapeutic effects are not completely understood. Transcription factor activator protein 1 (AP-1) is critical for the induction of neoplastic transformation and induction of multiple genes involved in inflammation and infection. We have used the JB6 mouse epidermal cell lines, a system that has been used extensively as an in vitro model for the study of tumor promotion and anti-tumor promotion, to study the anti-carcinogenesis effect of aspirin at the molecular level. Aspirin and aspirin-like salicylates inhibited the activation of AP-1 in the same dose range as seen for the inhibition of tumor promoter-induced transformation. The inhibition of AP-1 and tumor promoter-induced transformation in JB6 cells occurs through a prostaglandin independent- and an Erk1- or Erk2-independent pathway. The mechanism of AP-1 and transformation inhibition in this cell culture model may involve the elevation of H+ concentration. The inhibition effects on the activation of AP-1 activity by aspirin and aspirin-like salicylates may further explain the anti-carcinogenesis mechanism of action of these drugs.
 ...
PMID:Inhibition of activator protein 1 activity and neoplastic transformation by aspirin. 909 36

We retrospectively analyzed hospital morbidity and mortality following primary open lung surgery from August 1990 to December 1994 in 187 consecutive patients. 180 pulmonary resections and 7 exploratory thoracotomies were performed in 141 men and 46 women, with mean age 60.4 +/- 11.9 years. 142 patients were aged < 70 years (median 58.5), and 45 (25%) > 70 years (median 73). Tumor stage as well as preoperative ASA classification and FEV1 were similar in these age groups. No difference could be found in hospital morbidity of elderly compared to younger patients (> or = 70 years: 40%; < 70 years: 40.8%), but 30-day mortality was higher in elderly (8.9% versus 2.8% in younger subjects). Elderly patients who died postoperatively presented a higher preoperative risk (ASA 2.75) compared to nonfatal cases in the same age group (ASA 2.18). Morbidity and mortality increased with the extent of surgery; the 30-day mortality was nil in the group of wedge and segmental resections (0/23), 1.9% in lobectomies (2/106) and 7.8% in pneumonectomies (4/51). Our results in general match those of comparable centers in Switzerland and the international literature. Since the overall complication rate was not increased compared to younger patients, we assume that polymorbidity of single cases was the cause of higher mortality after extended open lung surgery in septuagenarians and octogenarians. In consequence, the scope of surgery should be reduced as far as possible. In addition, the perioperative risk for the senescent patient can be improved by identification of high risk cases. With this attitude we take the view that lung resection can honestly be recommended to the elderly also.
 ...
PMID:[How risky is lung resection today?--perioperative morbidity and mortality in open thorax surgery]. 914 97


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