Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Self-injurious behavior involving deliberate self-harm and suicide attempts by inmates while under custodial authority is a major problem for prisons and jails (prevalence, legal obligation for suicide prevention, and stress for officers). The differentiation of "serious" vs. "non-serious" and often manipulative suicide attempts as distinct phenomena, each with its own clinical features, is controversially discussed in current literature and a challenge for every diagnostician. If distinct clinical presentations and histories can be observed, an estimation of the seriousness of each act of self-injurious behavior can be simplified, whereby appropriate treatment of the individual case becomes possible. The aim of the study was to find differences between self-injurious behavior of "low seriousness" (i.e. low lethality and low suicidal intent) and of "high seriousness". Therefore, inmates showing self-injurious behavior were divided into subgroups of deliberate self-harm and suicide attempters on the basis of the act's intent and lethality. This was followed by a comparison of the clinical presentations of the individual inmates constituting the subgroups. Hence, 49 inmates showing self-injurious behavior were interviewed and tested with a variety of instruments (SCID-I and II, PCL-R, BDI-II, BHS, BSS, SIS, etc.), and their prison and health files were examined. The results indicate significant correlations between seriousness and some demographic, prison-related variables as well as different measures of depression. Negative, but nonsignificant correlations could be observed with regard to cluster B personality disorders. The PCL-R total score as well as PCL-R factor 1 showed a statistical trend for negative correlations with measures of seriousness. Inmates showing deliberate self-harm and suicide attempters seem to differ in a number of ways. Implications on how the individual prisoner should be treated are discussed.
 ...
PMID:Deliberate self-harm and suicide attempt in custody: distinguishing features in male inmates' self-injurious behavior. 1678

We previously reported that 4C8 monoclonal antibody (mAb) provides a costimulatory signal to human CD4+ T cells and consequently induces regulatory T (Treg) cells, which are hypo-responsive and suppress the polyclonal response of bystander CD4+ cells in a contact-dependent manner. In this study, we identified the antigen of 4C8 mAb as CD52. Costimulation with Campath-1H, a humanized anti-CD52 mAb, also induced Treg cells. Anti-CD52-induced Treg cells suppressed the proliferation of both CD4+ and CD8+ T cells provided with polyclonal or allogeneic stimulation. When Treg cells were induced from Staphylococcal enterotoxin B (SEB) treated cells, they suppressed the response to SEB more efficiently than that to another superantigen, SEA. Furthermore, anti-CD52-induced Treg cells could be expanded by culture with IL-2 followed by CD52-costimulation, and co-injection of expanded Treg cells suppressed lethal xenogeneic graft versus host disease (GvHD) reactions in SCID mice caused by human peripheral blood mononuclear cells (PBMCs).
 ...
PMID:CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells. 1679 37

We established a leukemia cell line derived from therapy-related acute myeloid leukemia with the t(11;19) by xenotransplantation into the NOD/SCID mouse with IL-2Rgamma(c)-/- (NOG mouse). The cell line, TRL-01, could be serially transplanted from mouse to mouse and also grown in an adherence-dependent manner on a murine bone marrow stroma cell line, HESS-5. TRL-01 had the same immunophenotype as the original leukemia cells: positive for CD13, CD33, CD11a, CD18, CD29, CD49d, CD49e, CD54, CD62L, and CD117, and negative for CD3, CD4, CD8, CD19, CD34, CD41a, CD41b, CD135, and myeloperoxidase. Translocation (11;19)(q23;p13) in both the original sample and TRL-01 generated MLL-ENL chimeric transcripts joining exon 6 and exon 4, respectively, which has a novel isoform. In cultures of TRL-01, addition of GM-CSF, SCF, and G-CSF and adhesion to fibronectin-coated plates promoted transient proliferation and survival, although they did not support long-term culture. Subcutaneous injection caused a tumor to form only when HESS-5 was coinjected at the same site. These results suggest that TRL-01 is a useful cell line for studying not only the leukemia-related biology of MLL-ENL but also the intercellular association between leukemia and stroma.
 ...
PMID:Establishment of a myeloid leukemia cell line, TRL-01, with MLL-ENL fusion gene. 1687 30

Canine mast cell tumors (MCTs) are the most common cutaneous tumors in the dog. They have a wide range of behaviour, which can make these tumors challenging to treat. Recently, mutations in c-kit proto-oncogene have been identified in several canine MCTs. Imatinib is the first member of a new class of agents that act by inhibiting particular tyrosin kinase enzymes, including KIT which is a product of the c-kit. In this study the efficacy of imatinib to reduce or abolish canine MCT [CMC-1] using xenografted MCT in severe combined immunodeficient [SCID] mice was evaluated. Imatinib was administered at doses of 200mg/kg and 100mg/kg once a day for one week. The antitumor responses in SCID mice with CMC-1 xenografts following treatment with imatinib were observed. Significant tumor regression occurred with 100mg/kg on days 7, 10, 14 and 21, and 200mg/kg on all days. Our results indicate that imatinib is effective against canine mast cell tumor in mouse xenograft models. Canine MCTs might be a potential target for imatinib therapy.
 ...
PMID:The tyrosine kinase inhibitor imatinib [STI571] induces regression of xenografted canine mast cell tumors in SCID mice. 1691 3

Bacterial CpG-containing (CpG) DNA promotes survival of murine macrophages and triggers production of proinflammatory mediators. The CpG DNA-induced inflammatory response is mediated via TLR9, whereas a recent study reported that activation of the Akt prosurvival pathway occurs via DNA-dependent protein kinase (DNA-PK) and independently of TLR9. We show, in this study, that Akt activation and survival of murine bone marrow-derived macrophages (BMM) triggered by CpG-containing phosphodiester oligodeoxynucleotides or CpG-containing phosphorothioate oligodeoxynucleotides was completely dependent on TLR9. In addition, survival triggered by CpG-containing phosphodiester oligodeoxynucleotides was not compromised in BMM from SCID mice that express a catalytically inactive form of DNA-PK. CpG DNA-induced survival of BMM was inhibited by the PI3K inhibitor, LY294002, but not by the MEK1/2 inhibitor, PD98059. The effect of LY294002 was specific to survival, because treatment of BMM with LY294002 affected CpG DNA-induced TNF-alpha production only modestly. Therefore, CpG DNA activates macrophage survival via TLR9 and the PI3K-Akt pathway and independently of DNA-PK and MEK-ERK.
 ...
PMID:CpG DNA activates survival in murine macrophages through TLR9 and the phosphatidylinositol 3-kinase-Akt pathway. 1698 83

Transforming growth factor beta 1 (TGF-beta1) is a potent tumor suppressor but, paradoxically, TGF-beta1 enhances tumor growth and metastasis in the late stages of cancer progression. This study investigated the role of TGF-beta type I receptor, ALK5, and three mitogen-activated protein kinases (MAPKs) in metastasis by breast cancer cell line MDA-MB-231. We show that autocrine TGF-beta signaling in MDA-MB-231 cells is required for tumor cell invasion and tumor angiogenesis. Expression of kinase-inactive ALK5 reduces tumor invasion and formation of new blood vessels within the tumor orthotopic xenografts in severe combined immunodeficiency (SCID) mice. In contrast, constitutively active ALK5-T204D enhances tumor invasion and angiogenesis by stimulating expression of matrix metalloproteinase MMP-9/gelatinase-B. Ablation of MMP-9 in ALK5-T204D cells by RNA interference (RNAi) reduces tumor invasion and tumor growth. Importantly, RNAi-MMP-9 reduces tumor neovasculature and increases tumor cell death. Induction of MMP-9 by TGF-beta-ALK5 signaling requires MEK-ERK but not JNK, p38 MAPK or Smad4. Dominant-negative MEK blocks and constitutively active MEK1 enhances MMP-9 expression. However, all three MAPK cascades (ERK, JNK and p38 MAPK) are required for TGF-beta-mediated cell migration. Collectively, our results show that TGF-beta-ALK5-MAPK signaling in tumor cells promotes tumor angiogenesis and MMP-9 is an important component of this program.
 ...
PMID:ALK5 promotes tumor angiogenesis by upregulating matrix metalloproteinase-9 in tumor cells. 1707 48

PTEN mutations are among the most frequent genetic alterations found in human prostate cancers. Our previous works suggest that although precancerous lesions were found in Pten heterozygous mice, cancer progression and metastasis only happened when both alleles of Pten were deleted. To understand the molecular mechanisms underlying the role of PTEN in prostate cancer control, we generated two pairs of isogenic, androgen receptor (AR)-positive prostate epithelial lines from intact conditional Pten knock-out mice that are either heterozygous (PTEN-P2 and -P8) or homozygous (PTEN-CaP2 and PTEN-CaP8) for Pten deletion. Further characterization of these cells showed that loss of the second allele of Pten leads to increased anchorage-independent growth in vitro and tumorigenesis in vivo without obvious structural or numerical chromosome changes based on SKY karyotyping analysis. Despite no prior exposure to hormone ablation therapy, Pten null cells are tumorigenic in both male and female severe combined immunodeficiency mice. Furthermore, knocking down PTEN can convert the androgen-dependent Myc-CaP cell into androgen independence, suggesting that PTEN intrinsically controls androgen responsiveness, a critical step in the development of hormone refractory prostate cancer. Importantly, knocking down AR by shRNA in Pten null cells reverses androgen-independent growth in vitro and partially inhibited tumorigenesis in vivo, indicating that PTEN-controlled prostate tumorigenesis is AR dependent. These cell lines will serve as useful tools for understanding signaling pathways controlled by PTEN and elucidating the molecular mechanisms involved in hormone refractory prostate cancer formation.
 ...
PMID:Murine cell lines derived from Pten null prostate cancer show the critical role of PTEN in hormone refractory prostate cancer development. 1761 63

Mammalian ovaries are endowed with a huge number of small oocytes in primordial follicles (primordial oocytes). The mechanism regulating initiation of oocyte growth and follicular development is not well understood. Several growth factors and cytokines are known to be involved in oocyte growth and follicular development. Herein, the involvement of KIT, a receptor tyrosine kinase, and its ligand, KIT ligand (KL), in the initiation of porcine oocyte growth was examined. At first, KIT expression was examined immunohistochemically in primordial oocytes from neonatal (10-20 days) and prepubertal (about 6 months) pigs. Similar expression of KIT was detected in all oocytes from both the neonatal and prepubertal pigs. Next, to examine the growth of primordial oocytes, ovarian tissues containing primordial oocytes were xenotransplanted into immunodeficient SCID mice. Primordial oocytes from the neonatal pigs grew with follicular development as described previously, whereas those from the prepubertal pigs did not initiate growth in the xenografts after 2 months. To stimulate the growth of primordial oocytes from the prepubertal pigs, they were cultured in a medium supplemented with KL (50 and 100 ng/ml) for 1 or 3 days before xenografting. After 2 months, however, the oocytes did not grow, and the primordial follicles did not develop, although a higher number of primordial oocytes survived in the KL-treated tissues. These results suggest that KIT-KL might not be associated with the growth initiation of porcine primordial oocytes, although they do enhance the survival of the oocytes.
 ...
PMID:KIT-KIT ligand in the growth of porcine oocytes in primordial follicles. 1796 40

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of primary effusion lymphoma (PEL) and of Kaposi's sarcoma. PEL is an aggressive proliferation of B cells with poor prognosis. We evaluated both in vitro and in vivo the potential role of angiogenic factors secreted by PEL cells, that is, their interaction with endothelial cells and their implication in the invasive behavior of tumoral cells. In vitro, PEL-induced angiogenesis is dependent on vascular endothelial growth factor (VEGF) and VEGF receptors. However, although PEL cells produce VEGF and basic fibroblast growth factor (b-FGF) transcripts, they only secrete VEGF in vitro. In vivo, very high levels of both VEGF and b-FGF were found in the ascitic fluid of NOD/SCID mice injected with PEL cells. We then show evidence of cell adhesion and gap junction-mediated heterocellular communication between PEL cells and endothelial cells. Finally, we show that PEL cells extravasate through the endothelial barrier and that the specific tyrosine kinase inhibitor of VEGF receptors, PTK-787/ZK-222584, the anti-VEGF antibody, bevacizumab or the gap junction inhibitor 18-alpha-glycyrrhetinic acid, partially attenuate PEL cell extravasation. Angiogenesis, cell adhesion and communication likely contribute to the development of PEL and represent potential therapeutic targets.
 ...
PMID:KSHV-transformed primary effusion lymphoma cells induce a VEGF-dependent angiogenesis and establish functional gap junctions with endothelial cells. 1809 12

Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODNs) function as powerful immune adjuvants by activating macrophages, dendritic cells, and B cells. However, the molecular recognition mechanism that initiates signaling in response to CpG-ODN has not fully been identified. We show in this study that peritoneal macrophages from SCID mice having mutations in the catalytic subunit of DNA-protein kinase (DNA-PKcs) were almost completely defective in the production of IL-10 and in ERK activation when treated with CpG-ODN. In contrast, IL-12 p70 production significantly increased. Furthermore, small interfering RNA (siRNA)-mediated knockdown of DNA-PKcs expression in the mouse monocyte/macrophage cell line RAW264.7 led to reduced IL-10 production and ERK activation by CpG-ODN. IL-10 and IL-12 p70 production, but not ERK activation, are blocked by chloroquine, an inhibitor of endosomal acidification. Endosomal translocation of CpG-ODN in a complex with cationic liposomes consisting of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) (CpG-DOTAP-liposomes) decreased IL-10 production and ERK activation, whereas the endosomal escape of CpG-ODN in a complex with cationic liposomes consisting of DOTAP and dioleyl-phosphatidylethanolamine (DOPE) (CpG-DOTAP/DOPE-liposomes) increased. In contrast, IL-12 p70 production was increased by CpG-DOTAP-liposomes and decreased by CpG-DOTAP/DOPE-liposomes. IL-10 production induced by CpG-DOTAP/DOPE-liposomes was not observed in macrophages from SCID mice. Thus, our findings suggest that DNA-PKcs in the cytoplasm play an important role in CpG-ODN-induced production of IL-10 in macrophages. In addition, DNA-PKcs-mediated production of IL-10 and IL-12 p70 can be regulated by manipulating the intracellular trafficking of CpG-ODN in macrophages.
 ...
PMID:Endosomal translocation of CpG-oligodeoxynucleotides inhibits DNA-PKcs-dependent IL-10 production in macrophages. 1817 19


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