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)

High-molecular-weight splice variants of the CD44 transmembrane protein family have been implicated in tumorigenesis and metastasis formation. By contrast, in certain tumors--for example, Burkitt's lymphoma, neuroblastomas, and prostate cancer--loss of CD44 expression seems to accompany transformation. Here we describe two modes of action of CD44 proteins. They can bind growth factors and present them to their authentic high-affinity receptors, and thus promote proliferation and invasiveness of cells. Under these conditions the CD44 proteins recruit ERM proteins--for example, ezrin or moesin--to their cytoplasmic tails, thereby producing links to the cytoskeleton. This mode of action could account for the tumor-promoting action of CD44 proteins. The second mode of action of CD44 proteins comes into play when cells reach confluent growth conditions. Under specific conditions, binding of another ligand, the ECM component hyaluronate, leads to the activation and binding to the CD44 cytoplasmic tail of the tumor suppressor protein merlin. The activation of merlin confers growth arrest, so-called contact inhibition. This function of CD44 proteins defines them as tumor suppressors. The type of action of CD44 on a given cell will depend on the isoform pattern of CD44 expressed, on the cellular equipment with ERM protein members, on the nature of the ECM, and on yet-unknown conditions.
 ...
PMID:CD44 acts both as a growth- and invasiveness-promoting molecule and as a tumor-suppressing cofactor. 1091 9

Sialomucin complex (SMC), a rat homologue of the human mucin MUC4, is a large membrane-bound mucin complex, originally isolated from highly metastatic ascites 13762 mammary adenocarcinoma cells. When overexpressed, SMC exerts potent anti-adhesive effects, which sterically disrupt molecular interactions for cell-cell and cell-ECM adhesions. SMC similarly suppresses anti-tumor immunity by inhibition of interactions between cytotoxic lymphocytes and target tumor cells. Previously, recombinant cDNAs for SMC were transfected and inducibly expressed in A375 human melanoma cells using a tetracycline-responsive expression system. In the current studies, we investigated the role of MUC4/SMC in tumor metastasis by regulating SMC expression of tumor transplants in vivo. Intravenous injection of SMC-overexpressing cells resulted in substantially greater lung metastasis than injection of SMC-repressed cells. Injection of SMC-overexpressing cells followed by in vivo downregulation of SMC did not lower the frequency of lung metastasis. Growth of the micrometastatic lesions was the same for all 3 cases in short-term (3-week) assays. Further, subcutaneous injection of A375 cells followed by in vivo induction of SMC overexpression within the solid tumor resulted in spontaneous distant metastasis. These studies suggest that SMC potentiates metastasis by contributing to the establishment of metastatic foci. These studies directly demonstrate for the first time that tumor metastasis can be modulated by the regulation of MUC4/SMC expression.
 ...
PMID:Potentiation of metastasis by cell surface sialomucin complex (rat MUC4), a multifunctional anti-adhesive glycoprotein. 1091 86

Hypocholesterolemia seems to represent a significant predictive factor of morbidity and mortality in critically ill patients. The authors, on the basis of recent literature data, aim to clarify the possible correlation between preoperative hypocholesterolemia and the risk of septic postoperative complications .205 patients undergoing to surgery for gastrointestinal diseases were the object of the study. Patients undergoing "minor" abdominal surgery or video-laparoscopic surgery and classified ASA III-IV were excluded. In all the patients, we considered retrospectively risk factors for postoperative septic complications as follows: preoperative blood concentration of cholesterol, malnutrition, obesity, diabetes, neoplasm, preoperative sepsis, type and duration of operations, antibiotics and regimen of use. Type and incidence of postoperative local or systemic septic complications were recorded. The patients have been stratified according to blood concentration of cholesterol and to the presence or absence of other risk factors. The incidence of postoperative sepsis was 35.1%. The highest incidence of postoperative septic complications (72.7%) was encountered, significantly (X2 = 7.6, p < 0.001), in the patients (11 cases, 5.9%) with cholesterol levels below 105 mg/dl). The results of this study seems to indicate a significant relationship between preoperative hypocholesterolemia and the incidence of septic complications after surgery. Moreover, evaluation of blood cholesterol levels before major surgery might represent a predictive factor of septic risk in the postoperative period.
 ...
PMID:[Blood levels of cholesterol and postoperative septic complications]. 1092 Apr 96

Aims of the study were: 1. to establish the prevalence of CD44 protein expression in human astrocytomas; 2. to compare the distribution of the extracellular matrix in these tumors; 3. to investigate the relation between CD 44, the extracellular matrix proteins and the histological grade of the tumor. CD44, Type IV Collagen (Col IV), Laminin (LN), Fibronectin (FN), and Tenascin (TN) expression were detected by immunohistochemistry in formalin fixed paraffin embedded tissue samples of 52 astrocytic tumors: 35 glioblastomas (GB), 7 Anaplastic astrocytomas (AA) and 10 astrocytomas (A). The localization of Col IV was observed in the basement membrane of the vessel walls in most of the astrocytomas (88.4%) with a similar pattern obtained with LN staining. 7 of 10 A (70%), 2 of 7 AA (28%) and 9 of 35 GB (25.7%) showed LN positivity. There was a negative correlation between LN expression and tumor grade (p=0.03). FN was either localized in the basement membrane or showed thick multi-layered immunoreactivity of the vessel walls. FN expression was seen in 6 A (60%), 4 AA (57%) and all of 35 GB (100%). The FN distribution was not uniform and its staining intensity showed decrease in GB. 3A (30%), 3 AA (42%), 27 GB (77.1%) showed TN expression in the vessel walls and in some tumor cells of 19 GBs. TN expression was positively correlated with the degree of vascular endothelial proliferation in GB (p<0.05). The expression of CD44s wasseen as plasma membrane positivity of glioma cells in 5 of 10A (50%), 3 of 7AA (42.3%) and 29 of 35 GB (82.8%). The intensity of immunoreaction was quite strong especially near the vessels. There was a good correlation between TN and CD44s expression in human astrocytic tumors (p=0.005). No relationship was observed between GFAP, ECM proteins and CD44s expression. Both CD44s and TN expression showed increase with malignancy in astrocytomas. These findings indicated that the histological malignancy of the astrocytomas was correlated with expression of TN and CD44s. It was suggested that in astrocytomas there was a biological relationship only between CD44 and TN, but none with the other ECM proteins. TN may play a role in angiogenesis in human astrocytic tumors.
 ...
PMID:The distribution of extracellular matrix proteins and CD44S expression in human astrocytomas. 1093 87

Fifteen minute exposure of primary cultures of cerebellar granule cells to micromolar concentrations of glutamate results in apoptotic cell death. Among the intracellular events triggered by glutamate, we identified two transcriptional factors, i.e. the p50 member of the NF-kappaB family and the tumor suppressor phosphoprotein p53, that are apparently linked by a sequential trascriptional program. We found that pretreatment of the cultures with aspirin (ASA), which inhibits NF-kappaB activation, resulted in a complete prevention of glutamate-induced p53 immunoreactivity. The same results were obtained pretreating the cells with a specific p53 antisense oligonucleotide. Both ASA and p53 antisense abolished glutamate-induced apoptosis. We also found that two other proteins, the cyclin dependent kinase inhibitor p21 and DNA mismatches repair MSH2, whose encoding genes are well known target of p53, were upregulated by glutamate. On these bases, we propose NF-kappaB, p53, p21 and MSH2 as relevant contributors of the glutamate-induced pro-apoptotic pathway.
 ...
PMID:Induction of p53 in the glutamate-induced cell death program. 1102 96

Aspirin therapy inhibits prostaglandin biosynthesis without directly acting on lipoxygenases, yet via acetylation of cyclooxygenase 2 (COX-2) it leads to bioactive lipoxins (LXs) epimeric at carbon 15 (15-epi-LX, also termed aspirin-triggered LX [ATL]). Here, we report that inflammatory exudates from mice treated with omega-3 polyunsaturated fatty acid and aspirin (ASA) generate a novel array of bioactive lipid signals. Human endothelial cells with upregulated COX-2 treated with ASA converted C20:5 omega-3 to 18R-hydroxyeicosapentaenoic acid (HEPE) and 15R-HEPE. Each was used by polymorphonuclear leukocytes to generate separate classes of novel trihydroxy-containing mediators, including 5-series 15R-LX(5) and 5,12,18R-triHEPE. These new compounds proved to be potent inhibitors of human polymorphonuclear leukocyte transendothelial migration and infiltration in vivo (ATL analogue > 5,12,18R-triHEPE > 18R-HEPE). Acetaminophen and indomethacin also permitted 18R-HEPE and 15R-HEPE generation with recombinant COX-2 as well as omega-5 and omega-9 oxygenations of other fatty acids that act on hematologic cells. These findings establish new transcellular routes for producing arrays of bioactive lipid mediators via COX-2-nonsteroidal antiinflammatory drug-dependent oxygenations and cell-cell interactions that impact microinflammation. The generation of these and related compounds provides a novel mechanism(s) for the therapeutic benefits of omega-3 dietary supplementation, which may be important in inflammation, neoplasia, and vascular diseases.
 ...
PMID:Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. 1103 10

During the past decades, the classic Whipple resection (cWhipple) and the pylorus-preserving Whipple (ppWhipple) operation have been advanced for the resection of cancer of the pancreatic head. However, no definitive answer exists as to whether the more conservative ppWhipple operation indeed equalizes the short- and long-term results of the cWhipple procedure. Therefore we conducted a randomized prospective trial in a nonselected series of consecutive patients. Demographics, diagnostic, intraoperative, and histologic findings (tumor type and tumor stage of these patients) as well as postoperative mortality, morbidity, and follow-up after discharge were analyzed. For statistical evaluation Kruskal-Wallis and chi-square tests were used where appropriate. Survival was analyzed according to Kaplan-Meier curves, and differences were examined using the log-rank test. From June 1996 to April 1999, a total of 114 patients with suspected pancreatic or periampullary tumors were prospectively randomized to undergo either a cWhipple or a ppWhipple (intention to treat) operation. Based on the inclusion and exclusion criteria, 77 of these patients were included in the final analysis. Forty had a cWhipple and 37 had a ppWhipple resection. There were no differences with regard to age, sex distribution, ASA classification, histologic classification, UICC stage, length of stay in the intensive care unit, and length of hospital stay. The ppWhipple group had a significantly shorter operative time, reduced blood loss, and fewer blood transfusions. There was no difference in mortality, but the cWhipple group showed a significantly higher total morbidity. The incidence of delayed gastric emptying was identical in both groups. For long-term follow-up, a total of 61 patients with histologically proven pancreatic or periampullary carcinoma were analyzed. There were no differences in tumor recurrence or in long-term survival at a median follow-up of 1.1 years (range 0.1 to 2.9 years). Our initial results demonstrate that the cWhipple and ppWhipple operation are equally radical. However, ppWhipple may be the procedure of choice for the treatment of pancreatic and periampullary cancer.
 ...
PMID:Randomized prospective trial of pylorus-preserving vs. Classic duodenopancreatectomy (Whipple procedure): initial clinical results. 1107 17

The aim of this study was to explore whether von Willebrand's factor (vWF) plays a role in the adhesion of human colon tumor cells to human endothelial cells in our coculture system. Cell colony density was evaluated basally (endothelial plus colon tumor cells) and following the addition of: purified vWF, vWF plus vWF-blocking antibodies, antibodies against various integrins and adhesion molecules (alpha2 b integrin, beta1 integrin, beta3 integrin, intercellular adhesion molecule-I, intercellular adhesion molecule-II, vitronectin receptor CD61 CD51, laminin alpha6/beta4 receptor), and various drugs inhibiting the hemostatic system (ticlopidine, heparin, acetyl salicylic acid [ASA], defibrotide, indobuphen, dipyridamole, sulfinpyrazone). Furthermore, vWF concentration was measured in the supernatant fluid of the coculture system basally and following the addition of the above-listed drugs. Cell colony density (as measured by light absorption) increased by 33% following the addition of vWF and returned to a value similar to the basal level with antibodies against vWF, while it did not change significantly following the addition of antibodies against the other integrins or adhesion molecules tested. The same parameter was reduced by 35% following the addition of ticlopidine, while it showed a smaller or no change with the other drugs tested. Similarly, vWF concentration in the cell coculture supernatant showed the greatest reduction (from 0.22 to 0.11 mg/mL) following the addition of ticlopidine. These data suggest that vWF mediates the adherence of human tumor cells to human endothelial cells and that ticlopidine interferes with this effect.
 ...
PMID:Von Willebrand's factor mediates the adherence of human tumoral cells to human endothelial cells and ticlopidine interferes with this effect. 1110 Aug 96

During tissue morphogenesis and tumor invasion, epithelial cells must undergo intercellular rearrangement in which cells are repositioned with respect to one another and the surrounding mesenchymal extracellular matrix. Using three-dimensional aggregates of squamous epithelial cells, we show that such intercellular rearrangements can be triggered by activation of beta1 integrins after their ligation with extracellular matrices. On nonadherent substrates, multicellular aggregates (MCAs) formed rapidly via E-cadherin junctional complexes and over time became compacted spheroids exhibiting a more epithelial phenotype. After MCAs were replated on culture substrates, the spheroids collapsed to yield tightly arranged cell monolayers. Cell-cell contact induced rapid elevation in E-cadherin levels, which was due to an increase in the metabolic stability of junctional receptors. During MCA remodeling of cell-cell adhesions, and monolayer formation, their E-cadherin levels fell rapidly. Similar behavior was obtained regardless of which ECM ligand-collagen type I, fibronectin, or laminin 1-MCAs were seeded on. In contrast, when seeded onto a matrix elaborated by squamous epithelial cells, cells in the MCA attached, spread, lost cell-cell junctions, and dispersed. Analysis identified laminin 5 as the active ECM ligand in this matrix, and MCA dispersion required functional beta1 integrin and specifically alpha3beta1. Furthermore, substrate-immobilized anti-integrin antibody effectively reproduced the epithelial-mesenchymal-like transition induced by the laminin 5 matrix. During the early stages of aggregate rearrangement and collapse, cells on laminin 5 substrates, but not those on collagen I substrates, exhibited intense cortical arrays of F-actin, microspikes, and fascin accumulation at their peripheral surfaces. These results suggest that engagement of specific integrin-ligand pairs regulates cadherin junctional adhesions during events common to epithelial morphogenesis and tumor invasion.
 ...
PMID:Integrin alpha3beta1 engagement disrupts intercellular adhesion. 1113 42

We have assessed 24 patients consecutively treated with cryosurgery and chosen according to the guidelines of the European Study Group of Urologic Cryosurgeons. Of the 24 patients (average age about 70, range 61-79), all were not considered candidates for radical prostatectomy, 9 (37%) were clinical stage cT2 N0M0, 15 (63%) cT3 N0M0 who had not received any prior treatment, except 1 patient (61 years old) who was treated with TCT and successive recurrence of the disease (cT2). Of the 24 chosen patients, 13 (55%) were over the age of 71, 11 (45%) had important factors of co-morbidity and an elevated risk of surgery (ASA 3). The average PSA was of 19.3 ng/ml (range 2.2-61). Gleason score was 2-5 in 9 cases, 6-7 in 14 and 8-10 in 1 case. In the follow-up, we evaluated serum PSA every 3 months and transrectal ultrasound and the echoguided prostatic biopsies at 6, 12 and 24 months. Post-operative complications included: ecchymosis and edema of external genitals (16/24), fever > 38 degrees C (1/24), sloughing syndrome (6/24), urinary tract infections (10/24) acute urine retention (1/24). In 2 cases, 6 months after treatment, a transrectal resection was carried out. After a follow-up at 6 months, the PSA was 0.4 ng/ml (range 0.1-0.9), in 1 case. In positive core biopsy out of 6 showed neoplastic cells with fibrous tissue; the patient had a PSA of 0.58 ng/ml. At 12 months there were 11 assessable patients. The average PSA was 0.3 ng/ml (range 0.1-0.9). At 24 months there were 4 assessable patients, 1 of 4 showed serum PSA level of 4 ng/ml and cancer in apical biopsy. Erectile dysfunction was assessed on 8 patients affective before surgery: 1 referred to sufficient erections at penetration (1/8, 12.5%). After removal of the catheter, 4 of the 20 patients suffered stress and urge incontinence with the use of 1 pad a day. In 1 case, 18 months from surgery, slight stress incontinence was found (1 pad/day). Cryoablation is an efficient method and is given to slight post-operative morbidity and no intra-operative mortality, also in patients with high risk for open surgery. Indications may be found in patients with the following conditions: older than 72 years, severe co-morbidity and high risk for surgery, neoplasia at high risk of progression, and disease recurrence after radiotherapy. Our case history is at the moment encouraging and a larger number of cases as well as longer follow-up are needed.
 ...
PMID:[Ultrasound-guided cryosurgery of the prostate: short- and long-term experience]. 1122 Oct 53


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