• 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
  • 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)
  • 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)
  • preclinical
  • Results from this preclinical study, along with data from the Phase 1 study in patients with solid tumors, suggest that ENMD-2076 may have potential therapeutic benefit in the treatment of colorectal cancer. (prnewswire.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. (prnewswire.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)
  • Through this study, we show that ENMD-2076 has activity against preclinical models of breast cancer with more robust activity against TNBC. (bio-medicine.org)
  • 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)
  • centrosomes
  • Aurora kinase B localizes to microtubules near kinetochores, specifically to the specialized microtubules called K-fibers, and Aurora kinase A (MIM 603072) localizes to centrosomes (Lampson et al. (wikipedia.org)
  • Cancer is defined by uncontrolled cell growth and malignant cells can undergo cell division with multipolar spindles because they can group multiple centrosomes into two spindles. (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)
  • 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)
  • activity
  • ENMD-2076 demonstrated robust antitumor activity against murine xenograft models of human colorectal cancer (CRC) established from both cell lines and primary human samples. (prnewswire.com)
  • 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)
  • 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)
  • ENMD-2076 has shown promising activity in Phase I clinical trials in solid tumor cancers, leukemia, and multiple myeloma. (drugs.com)
  • INCENP stimulates Aurora B kinase activity. (wikipedia.org)
  • Also, cells deficient in topoisomerase II show significantly reduced Aurora B kinase activity. (wikipedia.org)
  • colorectal cancer
  • Dr. Mark R. Bray , Vice President Research at EntreMed commented on the paper, "In addition to demonstrating the substantial efficacy of ENMD-2076 in xenograft models of colorectal cancer in their excellent and comprehensive study, Dr. Tentler and his colleagues have illustrated the potential utility of advanced, non-invasive imaging techniques such as DCE-MRI and PET in evaluating the compound's antitumor and antiangiogenic capabilities. (prnewswire.com)
  • In the Phase 1 study in which ENMD-2076 was used to treat patients with solid tumors, colorectal cancer patients were among the participants who showed clinical benefit by reductions in tumor volume and tumor markers. (prnewswire.com)
  • These benefits were demonstrated in patients with a variety of tumor types including melanoma, renal cell, ovarian and colorectal cancer. (drugs.com)
  • Hedgehog
  • 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)
  • liver
  • 6 months without progression or significant side effects) was achieved in patients with ovarian, liver, colorectal, renal cell, breast cancer and melanoma. (drugs.com)
  • 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)
  • Therapeutics
  • 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)
  • 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)
  • 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)
  • development
  • 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)
  • Ken Ren, Ph.D., EntreMed's Chief Executive Officer further commented, "One of the major challenges for the development of a target therapy for cancer is the identification of a responsive subtype with a predictive biomarker. (bio-medicine.org)
  • Phase
  • 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)
  • EntreMed, Inc. recently initiated a Phase 2 study of ENMD-2076 in triple-negative breast cancer. (bio-medicine.org)
  • 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)
  • metastasis
  • Dr. Jennifer R. Diamond of the University of Colorado School of Medicine, who led the study, commented, "Triple-negative breast cancer is an aggressive breast cancer subtype which carries a high risk of developing metastasis. (bio-medicine.org)
  • The breast cancer bone metastasis has activated TGF-β signaling, which contributes to the formation of these lesions. (wikipedia.org)
  • cell cycle
  • In this study, a diverse panel of twenty-nine breast cancer cell lines representative of the clinically defined breast cancer subtypes were exposed to ENMD-2076 and the effects on proliferation, apoptosis, and cell cycle distribution were evaluated. (bio-medicine.org)