Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viable cancer cells can commonly be recovered from surgical sites and venous blood during tumor resection. The adhesion of these cells to surrounding tissues may impact patient outcomes. Iatrogenic exposure to increased extracellular pressure modulates integrin binding affinity and stimulates colon cancer cell adhesion in vitro through an alpha-actinin-1-dependent signaling pathway. We hypothesized that preoperative small interfering RNA-mediated silencing of alpha-actinin-1 in tumor tissue could disrupt pressure-stimulated cancer cell adhesion to murine surgical wounds and thereby enhance subsequent tumor-free survival. Reducing alpha-actinin-1 in CT26 murine adenocarcinoma cells blocked cell adhesion to collagen in vitro and similarly inhibited pressure-induced CT26 implantation in murine surgical wounds in vivo. Surgical wound contamination with pressure-activated CT26 cells significantly reduced tumor-free survival compared to contamination with tumor cells maintained under ambient pressure. However, mice treated with pressure-activated CT26 cells preoperatively transfected with alpha-actinin-1-specific small interfering RNA displayed reduced surgical site implantation and increased tumor-free survival compared to mice exposed to pressure-activated cells expressing normal levels of alpha-actinin-1 protein. These results suggest that pressure activation of malignant cells promotes tumor development and impairs tumor-free survival. alpha-Actinin-1 may be an effective therapeutic target to inhibit perioperative pressure-stimulated tumor cell implantation.
 ...
PMID:SiRNA-mediated reduction of alpha-actinin-1 inhibits pressure-induced murine tumor cell wound implantation and enhances tumor-free survival. 1832 66

Several studies indicate that cancer-associated fibroblasts play a critical role in cancer cell invasion and metastasis, the hallmarks of malignancy. To better understand the mechanisms underlying such effects, we established a heterotypic model of human fibroblasts (primary colon fibroblasts and immortalized human dermal fibroblasts) in co-culture with human colon cancer cells (HCT-8/E11), using three-dimensional collagen type-I and Matrigel matrices. We report that TGF-beta is the unique and dominant factor to provide pro-invasive signals to HCT-8/E11 colon cancer cells from TGF-beta-treated human fibroblasts in three-dimensional collagen type I and Matrigel matrices. These effects are not mimicked or reversed by EGF or bFGF, and are associated with the TGF-beta-mediated induction of myofibroblast differentiation and functional markers, such as alpha-SMA, the haptotactic matrix molecule TNC, collagen type 1 maturation enzyme P4H, serine protease FAP, and myofibroblast contractility. Accordingly, TGF-beta induced a strong activation of RhoA and stress fiber formation in fibroblasts, with no impact on Rac1-GTP levels. In contrast, EGF down-regulated Rho-GTP levels in fibroblasts, giving permissive signals for Rac1 activation, fibroblast polarization, and invasion. Taken together, our data imply that TGF-beta and EGF exert invasive growth-promoting actions in human colon tumors through a differential and cumulative impact on the stromal and cancer cell compartments. Our data predict that inhibitors directed at this reciprocal molecular and cellular crosstalk will have therapeutic applications for targeting the invasive growth of human primary tumors and their metastatic spread.
 ...
PMID:Differential impact of TGF-beta and EGF on fibroblast differentiation and invasion reciprocally promotes colon cancer cell invasion. 1842 81

The use of biological technologies for the treatment of degenerative spinal diseases has undergone rapid clinical and scientific development. BMP strategies have gained wide support for an inherent potential to improve the ossification process. It has been extensively studied in combination with various techniques for spinal stabilisation from both anterior and posterior approach. We studied the fusion process after implantation of rhBMP-2 in 17 patients with degenerative lumbar spine diseases in combination with dorsal fixation with pedicle screws and poly-ether-ether-ketone (PEEK) interbody cages. We used 12 mg rhBMP-2 carried by collagen sponge, 6 mg in every cage. Patient follow up consisted of pre-operative radiographic and clinical evaluation. Similar post-operative evaluations were performed at 3 and 6 months. Clinical assessment demonstrated clear improvement in all patients despite evidence of vertebral endplate osteoclastic activity in the 3-month radiographs. The 6-month radiograph, however, confirmed evidence of fusion, and no untoward results or outcomes were noted. While previous studies have shown exclusively positive results in both fusion rates and process, our study demonstrated an intermediate morphology at 3 months during the ossification process using Induct Os in combination with peek-cages using a PLIF-technique. The transient resorption of bone surrounding the peek cage did not result in subsidence, pain or complication, and fusion was reached in all cases within a 6-month-controlled evaluation. Although there was no negative influence on clinical outcome, the potential for osteoclastic or metabolic resorption bears watching during the post-surgical follow up.
 ...
PMID:Posterior lumbar interbody fusion using rhBMP-2. 1935 27

Little is known about the stretching effects on the biochemical and morphological features of tendons submitted to a long period of immobilization. Our purpose was to evaluate the response of rat tendons to stretching procedures after immobilization. The animals were separated into five experimental groups: GI--control of immobilized and euthanized animals; GII--immobilized and euthanized animals; GIII--control of immobilized animals and afterward stretched or allowed free cage activity; GIV--immobilized and stretched animals; and GV--immobilized and allowed free cage activity. Analysis in SDS-PAGE showed no remarkable differences among the groups, but a prominent collagen band was observed in GV, as compared to GIV and the control group, both in the compression and tension regions. Hydroxyproline content was highest in the compression region of GII. No differences among the groups were observed in the tension region. In regard to the concentration of noncollagenous proteins, differences were detected only in the tension region, where larger concentrations were found in the GII. When GII and GIV were compared, highest values were found in the GII. A more abundant presence of sulfated glycosaminoglycans, especially chondroitin sulfate, was detected in GIV, at the compression region of tendons. The presence of dermatan sulfate was outstanding in the compression and tension regions of the GII and GV groups. In the Ponceau SS stained sections, analyzed under polarization microscopy, GII exhibited the highest disorganization of the collagen bundles, partially recovered after stretching or with only remobilization. Our results indicate that a revision in the stretching procedures, in terms of duration and periodicity of the sessions, could benefit the efficiency of the stretching in cases of previous immobilization of tendons.
 ...
PMID:Structural and biochemical analysis of the effect of immobilization followed by stretching on the calcaneal tendon of rats. 1908 45

Carbon monoxide (CO), long considered a toxic gas, has recently been shown to mediate anti-inflammatory effects in various animal models. The aim of this study was to investigate whether the inhalation of CO ameliorated collagen-induced arthritis (CIA) in mice. CIA was induced in female DBA/1 mice by the injection of an anti-type II collagen antibody and lipopolysaccharide. The CO treatment group was exposed to CO gas at a concentration of 200 ppm in a closed cage starting on the day of the injection with an anti-type II collagen antibody and throughout the remaining study period. The clinical arthritis scores was examined daily for swelling of the paws as a sign of arthritis. For histopathology, the sections of the hind legs were evaluated by hematoxylin-eosin staining. Moreover, we evaluated the expression of interleukin (IL)-1beta and monocyte chemoattractant protein-1 (MCP-1) mRNA in the hind paws. Both clinical arthritis scores as well as histological findings of joint inflammation were significantly reduced in mice treated with CO gas inhalation compared to untreated mice. Further, CO significantly inhibited the increased expression of IL-1beta and MCP-1 mRNA in paws at day 3 after the induction of arthritis. In conclusion, the inhalation of CO protected mice from the synovial inflammation of CIA. Based on these data, the beneficial effects of CO in murine RA model may be attributed to its anti-inflammatory properties.
 ...
PMID:Inhalation of carbon monoxide ameliorates collagen-induced arthritis in mice and regulates the articular expression of IL-1beta and MCP-1. 1921 26

The incidence of diastolic heart failure increases dramatically with age. We investigated the impact of long-term exercise training on age-related diastolic dysfunction. Old (25-month-old) male Fischer 344 rats were studied after 12 weeks of treadmill exercise training or sedentary cage life (N=7, in each group). We determined cardiac performance using a pressure-volume conductance catheter and magnetic resonance imaging. Collagen volume fraction (CVF) and myocardial collagen solubility by pepsin as an index of advanced glycation end products (AGEs) cross-linked collagen were measured. The maximal slope of systolic pressure increment (+dP/dt) and the slope of end-systolic pressure-volume relation were higher, and end diastolic volume (EDV), Delta EDV (the percentage of the EDV increment-to-baseline EDV) and the slope of end-diastolic pressure-volume relation were lower in training group. The maximal slope of diastolic pressure decrement (-dP/dt) and time constant of LV pressure decay (tau) had no difference. AGEs cross-linked collagen, not CVF was reduced by exercise training. Long-term exercise training appears to attenuate age-related deterioration in cardiac systolic function and myocardial stiffness and could be reduce in pathologic AGEs cross-linked collagen in myocardium.
 ...
PMID:Long-term exercise training attenuates age-related diastolic dysfunction: association of myocardial collagen cross-linking. 1927 Aug 10

The chemokine receptor CXCR4 and its ligand CXCL12 is overexpressed in the majority of tumors and is critically involved in the development and metastasis of these tumors. CXCR4 is expressed in malignant tumor cells whereas its ligand SDF-1 (CXCL12) is expressed mainly by cancer associated fibroblasts (CAF). Similarly to CXCR4, the chemokine CCL20 is overexpressed in variety of tumors; however its role and regulation in tumors is not fully clear. Here, we show that the chemokine receptor CXCR4 stimulates the production of the chemokine CCL20 and that CCL20 stimulates the proliferation and adhesion to collagen of various tumor cells. Furthermore, overexpression of CCL20 in tumor cells promotes growth and adhesion in vitro and increased tumor growth and invasiveness in vivo. Moreover, neutralizing antibodies to CCL20 inhibit the in vivo growth of tumors that either overexpress CXCR4 or CCL20 or naturally express CCL20. These results reveal a role for CCL20 in CXCR4-dependent and -independent tumor growth and suggest a therapeutic potential for CCL20 and CCR6 antagonists in the treatment of CXCR4- and CCL20-dependent malignancies.
 ...
PMID:Interaction between CXCR4 and CCL20 pathways regulates tumor growth. 1934 Feb 88

Exercise training (EX) following percutaneous transluminal coronary angiography (PTCA) reduces progression to restenosis and increases event-free survival rates. Our aim was to determine whether EX inhibits lesion development and/or alters the extracellular matrix (ECM) composition of the neointima (NI) in a porcine PTCA model. Miniature Yucatan swine were assigned to cage confinement (SED) or EX for 20 wk. After 16 wk, all animals underwent a PTCA procedure of the left anterior descending artery (LAD) and left circumflex artery (LCX), with subsequent placement of an externalized jugular catheter. Animals recovered for 2 days and then resumed the previous protocol of SED or EX. Twelve days following PTCA, all animals received an intravenous bromodeoxyuridine (BrdU) injection to label proliferating cells. At 28 days following PTCA, the animals were euthanized, the LAD and LCX excised, and underwent standard histological processing for total collagen, type I collagen, fibronectin, BrdU, and Verhoeff-van Gieson stain. Our results demonstrate that EX significantly decreased lesion size and NI proliferation (-48%) in the LAD (P < 0.05) but not the LCX. Furthermore, EX attenuated type I collagen expression only in LAD, whereas total collagen was increased (5.9%) and fibronectin was decreased (-7.9%) in the NI of both vessels (P < 0.05). In conclusion, EX following PTCA may increase event-free survival rates following PTCA by decreasing lesion size and altering ECM composition.
 ...
PMID:Exercise training decreases the size and alters the composition of the neointima in a porcine model of percutaneous transluminal coronary angioplasty (PTCA). 1955 53

Protein-based nanomedicine platforms for drug delivery comprise naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They are ideal for drug-delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug-delivery systems, including the ferritin/apoferritin protein cage, plant-derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms, including various protein cages, microspheres, nanoparticles, hydrogels, films, minirods, and minipellets. The protein cage is the most newly developed biomaterial for drug delivery and therapeutic applications. The uniform size, multifunctionality, and biodegradability push it to the frontier of drug delivery. In this Review, the recent strategic development of drug delivery is discussed with emphasis on polymer-based, especially protein-based, nanomedicine platforms for drug delivery. The advantages and disadvantages are also discussed for each type of protein-based drug-delivery system.
 ...
PMID:Protein-based nanomedicine platforms for drug delivery. 1957 30

The possible biochemical mechanism of gallium was studied in this paper. One-day-old hens were fed to up to 68 weeks on a control diet and diets containing gallium. Serum calcium and phosphorus, serum alkaline phosphatase, tartrate resistant acid phosphatase (TRAP), serum osteocalcin, homocysteine, C-terminal crosslinked telopeptides of collagen type I, and bone mineral content were measured, respectively. The beneficial effects of gallium supplementation on improvement of cage layer osteoporosis were attributable mainly to decrease TRAP activity, C-terminal crosslinked telopeptides of collagen type I level, plasma calcium and phosphate concentrations, and increase the mineral content in the bones and osteocalcin level in plasma.
 ...
PMID:Biochemical mechanism of gallium on prevention of fatal cage-layer osteoporosis. 1963 69


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