Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Embryo-derived tissues, such as umbilical cord (UC), can represent attractive sources of mesenchymal stem cells because their use is not related to any ethical issue. Abundant experimental evidence has already shown that Wharton's jelly contains cells able to differentiate in vitro into adipocytes, chondrocytes, osteocytes and neurons. Human UCs were obtained from term caesarean deliveries and processed within 24 h. Cells derived from the Wharton's jelly expressing mesenchymal markers, such as CD105, but not KDR and CD31 antigens, have been selected by positive and negative immunoseparation. These cells were characterized by an elongated shape and a good proliferation rate. Moreover, they were, at least in part, of fetal origin, as demonstrated by the expression of Sry mRNA. The expression of Myf5 and MyoD was detected after 7 and 11 days of in vitro myogenic induction, respectively. At two weeks from cell injection in the tibialis anterior muscle, previously damaged with bupivacaine, skeletal muscle appeared completely repaired and transplanted cells were present in the muscle for two weeks and differentiated into skeletal muscle cells, as demonstrated by the co-localization of HLA 1 and sarcomeric tropomyosine antigens. These observations provide the first demonstration that CD105(+)/CD31(-)/KDR(-) cells are able not only to differentiate in vivo towards the myogenic lineage, but also to contribute to the muscle regenerative process.
Int J Mol Med 2006 Dec
PMID:CD105(+) cells from Wharton's jelly show in vitro and in vivo myogenic differentiative potential. 1708 12

We hypothesize that compensatory lung growth after unilateral pneumonectomy in a murine model is, in part, angiogenesis dependent and can be altered using angiogenic agents, possibly through regulation of endothelial cell proliferation and apoptosis. Left pneumonectomy was performed in mice. Mice were then treated with proangiogenic factors [vascular endothelial growth factor (VEGF); basic fibroblast growth factor (bFGF)], VEGF receptor antibodies (MF-1, DC101), and VEGF receptor small molecule chemical inhibitors. Lung volume and mass were measured. The lungs were analyzed using immunohistochemistry by CD31 staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling, type II pneumocytes staining, and proliferating cell nuclear antigen. Compensatory lung growth was complete by postoperative day 10 and was associated with diffuse apoptosis of endothelial cells and pneumocytes. This process was accelerated by VEGF, such that growth was complete by postoperative day 4 with similar associated apoptosis. bFGF had no effect on lung growth. MF-1 and DC101 had no effect. The VEGF receptor small molecule chemical inhibitors also had no effect. VEGF, but not bFGF, accelerates growth. VEGF receptor inhibitors do not block growth, suggesting that other proangiogenic factors play a role or can compensate for VEGF receptor blockade. Diffuse apoptosis, endothelial cell and pneumocyte, occurs at cessation of both normal compensatory and VEGF-accelerated growth. Angiogenesis modulators may control growth via regulation of endothelial cell proliferation and apoptosis, although the exact relationship between endothelial cells and pneumocytes has yet to be determined. The fact that bFGF did not accelerate growth in our model when it did accelerate regeneration in the liver model suggests that angiogenesis during organ regeneration is regulated in an organ-specific manner.
Am J Physiol Lung Cell Mol Physiol 2007 Mar
PMID:Vascular endothelial growth factor accelerates compensatory lung growth after unilateral pneumonectomy. 1712 56

Cyclooxygenase-2 (COX-2) inhibitors are being developed as chemopreventive and anticancer agents. This study aimed to determine the biological effect of the COX-2 inhibitor celecoxib in pancreatic cancer as an early step to the further development of the agent in this disease. Eight patients scheduled for resection of an infiltrating adenocarcinoma of the pancreas were randomized to receive celecoxib at a dose of 400 mg twice daily or placebo for 5 to 15 days before the surgery. In addition, carcinomas from nine additional patients were xenografted in nude mice, expanded, and treated with vehicle or celecoxib for 28 days. Celecoxib markedly decreased the intra-tumor levels of prostaglandin E2 in patient carcinomas and in the heterotransplanted xenografts. However, this effect did not result in inhibition of cell proliferation or microvessel density (as assessed by Ki67 and CD31 staining). In addition, a panel of markers, including bcl-2, COX-1, COX-2, and VEGF, did not change with treatment in a significant manner. Furthermore, there was no evidence of antitumor effects in the xenografted carcinomas. In summary, celecoxib efficiently inhibited the synthesis of prostaglandin E2 both in pancreatic cancer surgical specimens and in xenografted carcinomas but did not exert evident antitumor, antiproliferative, or antiangiogenic effect as a single agent. The direct pancreatic cancer xenograft model proved to be a valuable tool for drug evaluation and biological studies and showed similar results to those observed in resected pancreatic cancer specimens.
Mol Cancer Ther 2006 Dec
PMID:Assessment of celecoxib pharmacodynamics in pancreatic cancer. 1717 27

The abnormal function of tyrosine kinase receptors is a hallmark of malignant gliomas. Tie2 receptor tyrosine kinase is a specific endothelial cell receptor whose function is positively regulated by angiopoietin 1 (Ang1). Recently, Tie2 has also been found in the nonvascular compartment of several tumors, including leukemia as well as breast, gastric, and thyroid cancers. There is, however, little information on the function of the Ang1/Tie2 pathway in the non-stromal cells within human tumors. We found that surgical glioblastoma specimens contained a subpopulation of Tie2+/CD31- and Tie2+/GFAP+ cells, suggesting that Tie2 is indeed expressed outside the vascular compartment of gliomas. Furthermore, analysis of a tissue array consisting of 116 human glioma samples showed that Tie2 expression in the neoplastic glial cells was significantly associated with progression from a lower to higher grade. Importantly, Ang1 stimulation of Tie2+ glioma cells resulted in increased adherence of the cells to collagen I and IV, suggesting that Tie2 regulates glioma cell adhesion to the extracellular matrix. Conversely, the down-regulation of Tie2 levels by small interference RNA or the addition of soluble Tie2 abrogated the Ang1-mediated effect on cell adhesion. In studying the expression of cell adhesion molecules, we found that Tie2 activation was related to the up-regulation of integrin beta1 levels and the formation of focal adhesions. These results, together with the reported fact that malignant gliomas express high levels of Ang1, suggest the existence of an autocrine loop in malignant gliomas and that a Tie2-dependent pathway modulates cell-to-extracellular matrix adhesion, providing new insights into the highly infiltrative phenotype of human gliomas.
Mol Cancer Res 2006 Dec
PMID:Expression of the receptor tyrosine kinase Tie2 in neoplastic glial cells is associated with integrin beta1-dependent adhesion to the extracellular matrix. 1718 82

Molecular morphologic tools exist for simultaneously visualizing immunophenotype and genotype of tumors, but are frequently hampered by a delicate balance between removing sufficient amount of the protein blocking full access of the probe to hybridize to target nucleic acids while still preserving sufficient target antigen for immunophenotyping. The result is often suboptimal, with either insufficiently visualized gene deletions and amplifications due to masking protein, or overdigestion of the protein target. Our purpose was to design and validate a gated genotyping assay that enables optimal and concomitant detection of both gene and protein. Using the proliferating endothelial cell compartment within gliomas organized in a tissue microarray (TMA), we tested the hypothesis that tyramide signal amplification (TSA) with deposition of a fluorochrome could be used during immunophenotyping, permitting sufficient protein digestion while insuring probe accessibility to nucleic acid target. The method was successfully validated using a TMA containing 38 glioma cases previously genotyped for EGFR amplification. CD31 positive endothelial cells were segregated via TSA-based Alexa-Fluor 647 immunofluorescence for analysis of EGFR amplification of the gliomas organized in the TMA. Enhanced immunoFISH (TSA) successfully segregates immunophenotypically-defined cell populations for gated genotyping.
J Mol Histol 2007 May
PMID:Genotyping of phenotypically defined cells in neoplasia: enhanced immunoFISH via tyramide signal amplification (TSA) segregates immunophenotypically-defined cell populations for gated genotyping. 1720 77

Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has shown antitumor activity by inhibiting tumor angiogenesis in preclinical and clinical studies. However, bevacizumab monotherapy does not induce complete tumor regression. Therefore, additional treatments must be combined with bevacizumab to promote tumor regression. We previously showed that melanoma differentiation associated gene-7 (mda-7) protein exerts potent antitumor and antiangiogenic activity. Thus, in this study, we investigated the therapeutic effects of mda-7 in combination with bevacizumab using lung cancer as a model. In vitro, treatment of human umbilical vein endothelial cells with conditioned medium from Ad-mda7 plus bevacizumab-treated lung tumor cells showed reduced VEGF ligand-receptor binding, and decreased cell survival, resulting in growth arrest and apoptosis. In vivo, treatment of subcutaneous lung tumor xenografts with bevacizumab plus Ad-mda7 resulted in significant tumor growth inhibition and improved survival compared to tumor growth in control mice. Furthermore, tumors in all the Ad-mda7 plus bevacizumab-treated mice completely regressed, and these were tumor free through the study's end. Molecular analysis showed enhanced tumor cell apoptosis and reduced VEGF and CD31 expression in Ad-mda7 plus bevacizumab-treated tumors. Thus, Ad-mda7 and bevacizumab treatment produces a synergistic and complete therapeutic effect against human lung cancer.
Mol Ther 2007 Feb
PMID:mda-7 In combination with bevacizumab treatment produces a synergistic and complete inhibitory effect on lung tumor xenograft. 1723 6

We aimed to optimize non-viral transfection of human stromal cell derived factor (SDF-1alpha) gene into skeletal myoblasts (SkM) and, transplant these cells to establish transient SDF-1alpha gradient to favor extra-cardiac stem cell translocation into infarcted heart. Optimized conditions for transfection of SDF-1alpha gene into syngenic SkM were achieved using FuGene6/phSDF-1alpha (3:2v/w, 4 h transfection) with 125 microM ZnCl(2) (p<0.001). After characterization for transgene overexpression by immunostaining, ELISA and PCR, the cells were transplanted in female rat model of myocardial infarction. Thirty-six rats were grouped (n=12/group) to receive 70 microl DMEM without cells (group-1) or containing 1.5 x 10(6) non-transfected (group-2) or SDF-1alpha transfected SkM (group-3). On day 4 post-transplantation (in 4 animals/group), marked expression of SDF-1alpha/sry-gene (p=0.003), total Akt, phospho-Akt and Bcl2 was observed in group-3. The number of CD31(+), C-kit(+) and CD34(+) cells was highest in group-3 hearts (p<0.01). Blood vessel density in group-3 was higher in both scar and peri-scar regions (p<0.001) as compared with other groups. Echocardiography showed improved indices of left ventricle contractile function and remodeling in group-3 (p<0.05) as compared with groups-1 and -2. We conclude that ex vivo SDF-1alpha transgene delivery promotes stem and progenitor cell migration to the heart, activates cell survival signaling and enhances angiomyogenesis in the infarcted heart.
J Mol Cell Cardiol 2007 Apr
PMID:Ex vivo delivered stromal cell-derived factor-1alpha promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium. 1735 33

Contained within the adult lung are differentiated mesenchymal cell types (cartilage, smooth muscle, and myofibrobasts) that provide structural support for airways and vessels. Alterations in the number and phenotype of these cells figure prominently in the pathogenesis of a variety of lung diseases. While these cells are thought to arise locally, progenitors have yet to be purified. In previous work, we developed a method for isolating progenitors from lung tissue: this technique takes advantage of the unique ability of cell populations enriched for somatic stem and progenitor activity to efflux the vital dye Hoechst 33342, a feature that permits isolation by flow cytometry-based procedures. Using this method, we determined that a rare population of mesenchymal progenitors resides within the CD45- CD31- Hoechst low fraction of the adult murine lung. Similar to other mesenchymal progenitors, these cells express Sca-1, CD106, and CD44; can be serially passaged; and can differentiate to smooth muscle, cartilage, bone, and fat. Overall, these findings demonstrate that a phenotypically distinct mesenchymal progenitor resides within the adult murine lung, and provide a scheme for their isolation and study.
Am J Respir Cell Mol Biol 2007 Aug
PMID:Isolation of an adult mouse lung mesenchymal progenitor cell population. 1739 89

The role of curcumin (diferuloylmethane), a proapoptotic compound, for the treatment of cancer has been an area of growing interest. Curcumin in its free form is poorly absorbed in the gastrointestinal tract and therefore may be limited in its clinical efficacy. Liposome encapsulation of this compound would allow systemic administration. The current study evaluated the preclinical antitumor activity of liposomal curcumin in colorectal cancer. We also compared the efficacy of liposomal curcumin with oxaliplatin, a standard chemotherapy for this malignancy. In vitro treatment with liposomal curcumin induced a dose-dependent growth inhibition [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt] and apoptosis [poly(ADP-ribose) polymerase] in the two human colorectal cancer cell lines tested (LoVo and Colo205 cells). There was also synergism between liposomal curcumin and oxaliplatin at a ratio of 4:1 in LoVo cells in vitro. In vivo, significant tumor growth inhibition was observed in Colo205 and LoVo xenografts, and the growth inhibition by liposomal curcumin was greater than that for oxaliplatin (P < 0.05) in Colo205 cells. Tumors from animals treated with liposomal curcumin showed an antiangiogenic effect, including attenuation of CD31 (an endothelial marker), vascular endothelial growth factor, and interleukin-8 expression by immunohistochemistry. This study establishes the comparable or greater growth-inhibitory and apoptotic effects of liposomal curcumin with oxaliplatin both in vitro and in vivo in colorectal cancer. We are currently developing liposomal curcumin for introduction into the clinical setting.
Mol Cancer Ther 2007 Apr
PMID:Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer. 1743 Nov 5

There is an association between obesity and heart failure associated with LV dysfunction. Adiponectin is an adipocyte-derived hormone that is downregulated in obesity. Here, we examined the role of adiponectin in cardiac remodeling after myocardial infarction with loss- and gain-of-function genetic manipulations in an experimental model. Myocardial infarction was created in adiponectin-deficient (APN-KO) and wild-type (WT) mice by the permanent ligation of the left anterior descending (LAD) artery. For some experiments, adenoviral vectors expressing adiponectin or beta-galactosidase were delivered systemically. Cardiac structure and function were assessed by echocardiographic and Millar catheter measurements. Myocardial capillary density was assessed by staining with anti-CD31 antibody. Myocyte apoptotic activity was determined by TUNEL-staining. Myocardial interstitial fibrosis was evaluated by Masson's trichrome staining. APN-KO mice showed exacerbated left ventricular (LV) dilation, myocyte hypertrophy and contractile dysfunction compared with WT mice at 4 weeks after LAD ligation. Impaired LV function in APN-KO mice was coupled to myocyte hypertrophy, increased apoptotic activity and interstitial fibrosis in the remote zone, and reduced capillary density in the infarct border zone. No difference in infarct size was observed between WT and APN-KO mice. Administration of adenovirus-mediated adiponectin in WT mice resulted in decreased LV dilatation and improved LV function that was associated with increased capillary density in the infarct border zone and decreased myocyte hypertrophy, diminished myocardial apoptosis and decreased interstitial fibrosis in the remote zone. These data suggest that adiponectin protects against the development of systolic dysfunction after myocardial infarction through its abilities to suppress cardiac hypertrophy and interstitial fibrosis, and protect against myocyte and capillary loss.
J Mol Cell Cardiol 2007 Jun
PMID:Adiponectin protects against the development of systolic dysfunction following myocardial infarction. 1749 64


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