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  • Targets
  • Indeed, proteins intimately involved in the regulation of the cell cycle ( 6 ), particularly cell cycle-associated kinases ( 7 , 8 ), have been suggested as possible new anticancer targets. (aacrjournals.org)
  • In fact, targeted agents, such as epidermal growth factor receptor inhibitor or antiangiogenic tyrosine kinase inhibitors, do shrink tumors in some patients (i.e., a cytotoxic effect), whereas emerging data suggest that exploitation of the molecular targets of standard chemotherapy (e.g., using ERCC1 as a predictive biomarker for platinum compounds) is now an achievable goal in the clinic. (aacrjournals.org)
  • Numerous kinetochore targets of Aurora kinases have been determined in organisms ranging from yeast to man. (wikipedia.org)
  • mitosis
  • Expression of Aurora B reaches a maximum at the G2-M transition, whereas Aurora B protein is most active during mitosis. (wikipedia.org)
  • This analysis showed that the association of Aurora B with centromeres is dynamic (Aurora B at the centromere is constantly exchanging with a pool of cytoplasmic Aurora B). The analysis of tagged Aurora B also suggested that it associates with spindle microtubules during anaphase of mitosis and this association significantly limits its mobility. (wikipedia.org)
  • In topoisomerase II-depleted cells, Aurora B and INCENP do not transfer to the central spindle in late mitosis. (wikipedia.org)
  • residues
  • Since the consensus sequence residues of a target substrate only make contact with several key amino acids within the catalytic cleft of the kinase (usually through hydrophobic forces and ionic bonds), a kinase is usually not specific to a single substrate, but instead can phosphorylate a whole "substrate family" which share common recognition sequences. (wikipedia.org)
  • The crystal structure of human Bub1 revealed the presence of a N-terminal tetratricopeptide repeat (TPR) domain and a C-terminal kinase domain (residues 784-1085), adopting a canonical kinase fold with two lobes. (wikipedia.org)
  • proteins
  • Compelling data demonstrate that centrosomes are implicated in cancer, because there are important oncogenic and tumor suppressor proteins that are localized in this organelle and drive centrosome aberrations. (dovepress.com)
  • 9 In humans, ciliopathies including primary ciliary dyskinesia, autosomal recessive primary microcephaly, polycystic kidney disease, and Bardet-Biedl disease are linked to defects caused by mutations in genes that encode centrosomal proteins. (dovepress.com)
  • reticulum (ER) can be particularly affected by the presence of mutations in secretory proteins or by dynamic changes in the cellular microenvironment, events which are often encountered in cancers. (exposed-skin-care.net)
  • Ovarian
  • Both partial responses were observed in platinum resistant ovarian cancer patients. (drugs.com)
  • 18 of the 20 ovarian cancer patients had some reduction in the tumor marker, CA-125. (drugs.com)
  • 6 months without progression or significant side effects) was achieved in patients with ovarian, liver, colorectal, renal cell, breast cancer and melanoma. (drugs.com)
  • In addition, encouraging clinical efficacy was seen in advanced and refractory ovarian cancer patients with both radiographic and CA-125 responses. (drugs.com)
  • ENMD-2076 is currently in a multi-center Phase 2 study in ovarian cancer patients, as well as in Phase 1 studies in multiple myeloma and leukemia. (drugs.com)
  • Although ovarian cancer was chosen for the initial Phase 2 study, these results demonstrate that ENMD-2076 is active in patients with other solid tumors and are consistent with the preclinical results," commented Dr. Carolyn F. Sidor , EntreMed's Vice President and Chief Medical Officer. (drugs.com)
  • EntreMed initiated a multi-center Phase 2 study for ENMD-2076 in ovarian cancer patients in 2010. (drugs.com)
  • Ovarian cancer was selected as the initial Phase 2 indication based on results from the Phase 1 study in patients with solid tumors in which the clinical benefit of ENMD-2076 was observed in this patient population. (drugs.com)
  • These benefits were demonstrated in patients with a variety of tumor types including melanoma, renal cell, ovarian and colorectal cancer. (drugs.com)
  • ROCKVILLE, Md. , June 3, 2011 /PRNewswire/ -- EntreMed, Inc. (Nasdaq: ENMD), a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer today announced the presentation of clinical data for its Phase 2 study with ENMD-2076 in platinum-resistant ovarian cancer patients. (drugs.com)
  • The trial was an open-label, single-arm, multi-center-study of ENMD-2076 dosed orally as a single agent in patients with platinum-resistant recurrent ovarian, peritoneal or tubal cancer. (drugs.com)
  • Dr. Matulonis commented on the results of the study, "ENMD-2076 has demonstrated impressive anti-cancer activity in platinum-resistant ovarian cancer which is notoriously difficult to treat, and these patients have few options. (drugs.com)
  • EntreMed's chief medical officer, Carolyn F. Sidor , M.D., M.B.A., added, "These results are very encouraging as they support further development of ENMD-2076 and also help us clarify its developmental path in ovarian cancer. (drugs.com)
  • We are currently designing the next clinical trial in this indication and look forward to opportunities to make ENMD-2076 available to ovarian cancer patients in the future. (drugs.com)
  • While ENMD-2076 is currently in a Phase 2 trial in ovarian cancer, preclinical and clinical activities are ongoing in assessing the compound's applicability in other forms of cancer. (drugs.com)
  • distinct
  • While the catalytic domain of these kinases is highly conserved, the sequence variation that is observed in the kinome (the subset of genes in the genome that encode kinases) provides for recognition of distinct substrates. (wikipedia.org)
  • aneuploidy
  • In this brief review, the various aspects of aneuploidy with special emphasis on its mechanism of development and impact on progression of cancer are discussed. (bmj.com)
  • associate
  • Although microbiome studies in humans are important to associate unique compositions of the intestinal microbiome with different disease claims studies in animal models under carefully controlled conditions present some advantages. (exposed-skin-care.net)
  • mutations
  • In humans, the activating mutations of miR-17~92 have been identified in non-Hodgkin's lymphoma, whereas the miRNA constituents of the clusters are overexpressed in a multiple cancer types. (wikipedia.org)
  • inhibition
  • Inhibition of Aurora B due to loss of topoisomerase II seems to depend on BubR1 activity (see below). (wikipedia.org)
  • Inhibition of Aurora B function by RNA interference or microinjection of blocking antibodies impairs the alignment of chromosomes at the equator of the mitotic spindle. (wikipedia.org)
  • Aurora B inhibition may lead to an increase in the number of syntelic attachments (sister chromatid pairs in which both sister kinetochores are attached to microtubules radiating from the same spindle pole). (wikipedia.org)
  • Raf inhibition has become the target for new anti-metastatic cancer drugs as they inhibit the MAPK cascade and reduce cell proliferation. (wikipedia.org)
  • spindle
  • Specifically, Aurora B localizes to the chromosomes in prophase, the centromere in prometaphase and metaphase, and the central mitotic spindle in anaphase. (wikipedia.org)
  • Indirect immunofluorescence showed that Aurora B and EB1 colocalize during anaphase on the central spindle and in the midbody during cytokinesis. (wikipedia.org)
  • Multipolar spindles are spindle formations characteristic of cancer cells. (wikipedia.org)
  • Aurora 1) functions in the attachment of the mitotic spindle to the centromere. (wikipedia.org)
  • liver
  • Human ATF6 cDNA was amplified by PCR from human Rasagiline manufacture liver total cDNA and cloned into p3FLAG-CMV7.1 vector within the HindIII/SalI restriction sites. (exposed-skin-care.net)
  • chromosomes
  • Normal human somatic cells have 23 pairs of chromosomes. (bmj.com)
  • In cancer cells, it has been observed that the formation of the spindles comes before when compared to the chromosomes. (wikipedia.org)
  • centrosome
  • All of this emerging evidence suggests that targeting centrosome aberrations may be a future avenue for therapeutic intervention in cancer research. (dovepress.com)
  • activity
  • The Company's other therapeutic candidates include MKC-1, an oral cell-cycle regulator with activity against the mTOR pathway currently in multiple Phase 2 clinical trials for cancer, and ENMD-1198, a novel antimitotic agent currently in Phase 1 studies in advanced cancers. (drugs.com)
  • Also, cells deficient in topoisomerase II show significantly reduced Aurora B kinase activity. (wikipedia.org)
  • RNAi
  • RNAi mediated depletion of human Bub1 has indicated function in correct metaphase congression. (wikipedia.org)
  • isoforms
  • The p63 factor is involved in inhibiting EMT and reduction of certain p63 isoforms may be important in the development of epithelial cancers. (wikipedia.org)
  • progression
  • EMT has also been shown to occur in wound healing, in organ fibrosis and in the initiation of metastasis in cancer progression. (wikipedia.org)
  • Since EMT in cancer progression recaptures EMT in developmental programs, many of the EMT-TFs are involved in promoting metastatic events. (wikipedia.org)
  • novel
  • The Molecular Cancer Therapeutics manuscript is the culmination of several intensive years of work by a dedicated team, who were able to show through a series of rigorous experiments that ENMD-2076 is a highly active, well-tolerated compound with a novel mechanism of action involving both antiangiogenic and antiproliferative components. (drugs.com)
  • cDNA
  • Human ATF6 cDNA was digested with PvuII and subsequently ligated in the p3FLAG vector. (exposed-skin-care.net)
  • The dominant negative Sar1 [Sar1(DN)] plasmid was a kind gift from J. Rasagiline manufacture A. Lippincott-Schwartz (NIH, Bethesda, MD). To construct an siRNA-resistant PDIA5 cDNA (PDIA5r), the human PDIA5 cDNA was amplified by PCR and subcloned in pGEM-T Easy plasmid. (exposed-skin-care.net)
  • developmental
  • Based on the biological context, EMT has been categorized into 3 types : developmental (Type I), fibrosis and wound healing (Type II), and cancer (Type III). (wikipedia.org)
  • pathway
  • The phosphatidylinositol 3' kinase (PI3K)/AKT axis, Hedgehog signaling pathway, nuclear factor-kappaB and Activating Transcription Factor 2 have also been implicated to be involved in EMT. (wikipedia.org)
  • Wnt signaling pathway regulates EMT in gastrulation, cardiac valve formation and cancer. (wikipedia.org)
  • Activation of Wnt pathway in breast cancer cells induces the EMT regulator SNAIL and upregulates the mesenchymal marker, vimentin. (wikipedia.org)
  • Also, active Wnt/beta-catenin pathway correlates with poor prognosis in breast cancer patients in the clinic. (wikipedia.org)
  • Targets
  • Indeed, proteins intimately involved in the regulation of the cell cycle ( 6 ), particularly cell cycle-associated kinases ( 7 , 8 ), have been suggested as possible new anticancer targets. (aacrjournals.org)
  • In fact, targeted agents, such as epidermal growth factor receptor inhibitor or antiangiogenic tyrosine kinase inhibitors, do shrink tumors in some patients (i.e., a cytotoxic effect), whereas emerging data suggest that exploitation of the molecular targets of standard chemotherapy (e.g., using ERCC1 as a predictive biomarker for platinum compounds) is now an achievable goal in the clinic. (aacrjournals.org)
  • Numerous kinetochore targets of Aurora kinases have been determined in organisms ranging from yeast to man. (wikipedia.org)
  • mitosis
  • Expression of Aurora B reaches a maximum at the G2-M transition, whereas Aurora B protein is most active during mitosis. (wikipedia.org)
  • This analysis showed that the association of Aurora B with centromeres is dynamic (Aurora B at the centromere is constantly exchanging with a pool of cytoplasmic Aurora B). The analysis of tagged Aurora B also suggested that it associates with spindle microtubules during anaphase of mitosis and this association significantly limits its mobility. (wikipedia.org)
  • In topoisomerase II-depleted cells, Aurora B and INCENP do not transfer to the central spindle in late mitosis. (wikipedia.org)
  • Gene
  • The underlying mechanism appears to be mediated by SphK1 induced upregulation of select gene transcription programs such as that of CBP/p300 and PCAF, two histone acetyl transferases (HAT), and the down regulation of cell cycle dependent kinase inhibitor genes such as p27kip1 and p21cip1. (docplayer.net)
  • The single survivin gene can give rise to four different alternatively spliced transcripts: Survivin, which has a three-intron-four-exon structure in both the mouse and human. (wikipedia.org)
  • inhibitor
  • Only one HDAC inhibitor, suberonylanilide hydroxamic acid (SAHA), marketed as Zolinza (vorinostat) has been approved by US Foods and Drugs Administration (FDA) for the treatment of cutaneous T-cell lymphoma (http://www.cancer.gov/cancertopics/druginfo/fdavorinostat) . (docplayer.net)
  • Even though the first Bcr-Abl TK inhibitor was named "the magic bullet" to cure cancer by TIME magazine, a second generation of Bcr-Abl TKI was subsequently developed to combat the initial resistance that emerged. (wikipedia.org)
  • With a replacement of the imidazole group with a benzamido group, the compound's specificity increased while its activity as a kinase inhibitor remained the same. (wikipedia.org)
  • microRNA
  • Mir-126 is a human microRNA that is expressed only in endothelial cells, throughout capillaries as well as larger blood vessels, and acts upon various transcripts to control angiogenesis. (wikipedia.org)
  • role
  • Conclusions/Significance: The lipid kinase SphK1 plays a positive and essential role in the growth and development of malignant mesothelioma and is therefore a likely therapeutic target. (docplayer.net)
  • Molecular
  • CML has a well defined molecular target and relatively selective therapies aimed at that target, which is not the case for the majority of cancers and chemotherapies today. (wikipedia.org)
  • known
  • EGFL7 is known to be involved in cell migration and blood vessel formation, making EGFL7 and mir-126 opportune targets for disease, such as cancers, which require the continual formation of blood vessels to supply the tumour with nutrients and cell migration pathways to mediate tissue invasion. (wikipedia.org)
  • disease
  • The frequency of the SNP varies between different ethnic backgrounds and potentially is related to the differential acquisition of human disease. (wikipedia.org)
  • activation
  • Inhibition of cancer progression occurs through mir-126s negative control of proliferation, migration, invasion and cell survival, while mir-126 also may support cancer progression through the promotion of blood vessel formation and inflammation at the site of activation. (wikipedia.org)
  • phase
  • In humans Bub1 accumulates gradually during G1 and S phase of the cell cycle, peaks at G2/M, and drops dramatically after mitosis. (wikipedia.org)