Filtered By:
Management: Funding
This page shows you your search results in order of date. This is page number 2.
Order by Relevance | Date
Total 58 results found since Jan 2013.
CD55 and CD59 Can Limit the Anti-Tumor Efficacy of Daratumumab in Natural Killer/T-Cell Lymphoma
In this report we show that subsequent testing in an NKTL mouse xenograft model confirms the potency of Daratumumab in vivo as evidenced by the inhibition in tumour progression and prolongation of mouse survival. When treatment was continued over a month, some tumors began to rapidly enlarge ('Resistant') while the rest remained similar or smaller ('Sensitive') than the tumour volume at the initiation of Daratumumab treatment. An mRNA analysis comparing 'Resistant' and 'Sensitive' tumors showed that while both tumours bore similar levels of CD38 expression, resistant tumours displayed an upregulation of complement inhibito...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mustafa, N., Nee, A. H. F., Chooi, J. Y., Toh, S. H. M., Hee, Y. T., Selvarajan, V., Zhou, L., Yang, J., Chng, W. J. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents: Poster I Source Type: research
Targeted Delivery of CpG-Mir-146a Mimic Oligonucleotides As a Therapeutic Strategy to Reduce NF-Kb-Mediated Pathogenic Inflammation and Myeloid Leukemia Progression
NF-kB signaling plays central role in the regulation of immune cell activity. The microRNA-146a-5p (miR-146a) provides negative feedback inhibition of the NF-kB pathway to prevent either excessive immunity, such as cytokine release syndrome. Low expression of miR-146a is also implicated in certain types of leukemia, especially in del(5q)-syndrome myelodysplastic and acute myeloid leukemia (MDS/AML). While miR-146a is a potential therapeutic target, the lack of efficient miRNA delivery methods limits clinical translation. We previously developed a strategy for targeted delivery of oligonucleotide therapeutics, such as siRNA...
Source: Blood - November 21, 2018 Category: Hematology Authors: SU, Y.-L., Zhang, Z., Mann, M., Wang, X., Nguyen, L. X. T., Zhang, B., Li, L., Swiderski, P., Boldin, M., Forman, S. J., Marcucci, G., Kortylewski, M. Tags: 802. Chemical Biology and Experimental Therapeutics: Poster II Source Type: research
MDM2 and Aurora Kinase a Contribute to SETD2 Loss of Function in Advanced Systemic Mastocytosis: Implications for Pathogenesis and Treatment
The SETD2 gene encodes the only methyltransferase responsible for histone H3 lysine 36 trimethylation (H3K36Me3) in humans. H3K36me3 play a key role in preserving the fidelity of transcription elongation and splicing. In addition, SETD2/H3K36me3 have more recently been implicated in the maintenance of genomic integrity by regulating homologous recombination (HR) repair, Mismatch Repair (MMR) mitotic spindle assembly and chromosome segregation. SETD2 deletions and/or inactivating mutations occur in many solid tumors and have recently been found also in acute leukemias. We have reported that the HMC-1.1 and -1.2 mast cell le...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mancini, M., Monaldi, C., De Santis, S., Papayannidis, C., Rondoni, M., Bavaro, L., Martelli, M., Maria Chiara, A., Curti, A., Ficarra, E., Paciello, G., Fontana, M. C., Zanotti, R., Bonifacio, M., Scaffidi, L., Pagano, L., Criscuolo, M., Albano, F., Cice Tags: 635. Myeloproliferative Syndromes: Basic Science: Poster I Source Type: research
SLN124, a Galnac-siRNA Conjugate Targeting TMPRSS6, for the Treatment of Iron Overload and Ineffective Erythropoiesis Such As in Beta-Thalassemia
Accumulation of excess iron in tissues causes organ damage and dysfunction and may lead to serious clinical consequences including liver cirrhosis, diabetes, growth retardation and heart failure. Iron overload is a major health threat in iron loading anemias, like beta-thalassemia, myelodysplastic syndrome and in hereditary hemochromatosis. In patients with beta-thalassemia major, iron overload develops due to frequent blood transfusions to control the severe anemia. In addition, iron overload also occurs in patients with beta thalassemia intermedia (non-transfusion dependent beta-thalassemia). In the later cases, iron ove...
Source: Blood - November 21, 2018 Category: Hematology Authors: Altamura, S., Altamura, S., Muckenthaler, M. U., Dames, S., Frauendorf, C., Schubert, S., Aleku, M., Vadolas, J., Grigoriadis, G., Zugel, U. Tags: 102. Regulation of Iron Metabolism: Poster II Source Type: research
Overexpressed Melk Promotes the Stability of EZH2 through Phosphorylation in Natural Killer/T Cell Lymphoma (NKTL)
In this study, we examined EZH2 protein turnover mechanisms in the NKTL context.The serine/threonine kinase Melk is one of the overexpressed genes in NKTL patient samples and cell lines, and the interaction between Melk and EZH2 was established by co-immunoprecipitation. Inhibition of Melk using inhibitor or siRNA both resulted in a decrease of EZH2 protein levels in NKTL cells, whereas there was no change in the mRNA level of EZH2, suggesting that Melk regulated EZH2 at the protein level. Next, we observed a change of EZH2 ubiquitination upon manipulation of Melk expression.Next, in order to confirm that Melk truly affect...
Source: Blood - November 21, 2018 Category: Hematology Authors: Li, B., Kappei, D., Yan, J., Eichhorn, P., Ng, S. B., Chng, W. J. Tags: 622. Lymphoma Biology-Non-Genetic Studies: Poster II Source Type: research
Musashi 2 Is Overexpressed in Poor Outcome CLL Patients and Their Proliferative Fraction and Silencing This Gene Induces Apoptosis and Increases Cell Adhesion and Movement
The growth of CLL cells stems from a small fraction of dividing CD5+B cells. The size and rate of growth of this proliferative fraction (PF) correlates directly with poor outcome prognostic markers and inversely with time-to-first-treatment. Furthermore, since dividing cells upregulate DNA mutators (AID and APOBEC), the PF can acquire new DNA abnormalities that can lead to more lethal disease. Hence, cells of the PF are important targets for therapy.By gene expression profile analysis, we found that Musashi 2 (MSI2) is highly expressed in the PF (CXCR4DimCD5Bright) compared with the resting fraction (RF) that expresses the...
Source: Blood - November 21, 2018 Category: Hematology Authors: Palacios, F., Yan, X.-J., Ferrer, G., Barrientos, J. C., Kolitz, J. E., Allen, S. L., Kanti R., R., Chiorazzi, N. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster I Source Type: research
Concomitant Targeting of FLT3 and BTK with CG'806 Overcomes FLT3-Inhibitor Resistance through Inhibition of Autophagy
Fms-like tyrosine kinase 3 (FLT3)-targeted therapy represents an important paradigm in the management of patients with highly aggressive FLT3 mutated acute myeloid leukemia (AML). However, clinical efficacy is usually transient and followed by emergence of resistance to FLT3-inhibitors (Borthakur et al., 2011; Cortes et al., 2013; Zhang et al., 2008). Such resistance often results from acquired mutations of TKD, which are frequently identified in D835, Y842 and F691 residues (Smith et al., 2015; Smith et al., 2012; Zhang et al., 2014). It was reported that the FLT3-ITD-targeting drug sorafenib can induce autophagy in human...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, W., Yu, G., Zhang, H., Ly, C., Yuan, B., Ruvolo, V., Piya, S., Bhattacharya, S., Zhang, Q., Borthakur, G., Battula, V. L., Konopleva, M. Y., Rice, W. G., Andreeff, M. Tags: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster II Source Type: research
Cirmtuzumab Inhibits Non-Canonical Wnt Signaling without Enhancing Canonical Wnt/{beta}-Catenin Signaling in Chronic Lymphocytic Leukemia
In this study, we examined whether genetic silencing of ROR1 or inhibition of ROR1-signaling also could influence canonical Wnt signaling. To inhibit ROR1 signaling we used the humanized anti-ROR1 mAb cirmtuzumab, which is being evaluated in patients with CLL (Choi MY, et al, Cell Stem Cell, 22:951, 2018). Surprisingly, we found that CRISPR/Cas9 deletion of ROR1 in 293T cells also could enhance the capacity of Wnt3a to activate canonical Wnt-signaling, albeit to a lesser extent than CRISPR/Cas9 deletion of ROR2; conversely, re-introduction of ROR1 into ROR1-deleted 293T cells suppressed Wnt3a-induced activation of canonica...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, H., Zhang, S., Ghia, E. M., Choi, M. Y., Zhang, J., Chen, L., Widhopf II, G. F., Rassenti, L. Z., Kipps, T. J. Tags: 605. Molecular Pharmacology, Drug Resistance-Lymphoid and Other Diseases: Poster II Source Type: research
Heterogeneous nuclear ribonucleoprotein C1 may control miR-30d levels in endometrial exosomes affecting early embryo implantation
AbstractSTUDY QUESTIONIs there a specific mechanism to load the microRNA (miRNA), hsa-miR-30d, into exosomes to facilitate maternal communication with preimplantation embryos?SUMMARY ANSWERThe heterogeneous nuclear ribonucleoprotein C1 (hnRNPC1) is involved in the internalization of endometrial miR-30d into exosomes to prepare for its subsequent incorporation into trophectoderm cells.WHAT IS KNOWN ALREADYOur group previously described a novel cell-to-cell communication mechanism involving the delivery of endometrial miRNAs from the maternal endometrium to the trophectoderm cells of preimplantation embryos. Specifically, hu...
Source: Molecular Human Reproduction - May 29, 2018 Category: Molecular Biology Source Type: research
Expression of GRIM-19 in unexplained recurrent spontaneous abortion and possible pathogenesis
AbstractSTUDY QUESTIONIs aberrant expression of gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) associated with unexplained recurrent spontaneous abortion (URSA)?SUMMARY ANSWERGRIM-19 deficiency may regulate regulatory T cell/T helper 17 cell (Treg/Th17) balance partly through reactive oxygen species (ROS) –mammalian target of rapamycin (mTOR) signaling axis in URSA.WHAT IS KNOWN ALREADYImmunological disorders may cause impaired maternal immune tolerance to the fetus and result in fetal rejection. The differentiation of Treg and Th17 cells is controlled by phosphoinositide 3-kinase (PI3K)/Akt/mTOR...
Source: Molecular Human Reproduction - May 11, 2018 Category: Molecular Biology Source Type: research
Secreted frizzled-related protein 2 (SFRP2) expression promotes lesion proliferation via canonical WNT signaling and indicates lesion borders in extraovarian endometriosis
This study was funded by the Academy of Finland and by Tekes: Finnish Funding Agency for Innovation. The authors have no conflict of interest to declare.
Source: Human Reproduction - February 15, 2018 Category: Reproduction Medicine Source Type: research
Changes in keratin 8/18 expression in human granulosa cell lineage are associated to cell death/survival events: potential implications for the maintenance of the ovarian reserve
This study describes, for the first time, the existence of sub-populations of primordial follicles on the basis of K8/K18 expression in granulosa cells, and that their proportions change with age. While a progressive increase in K8/K18 expression cannot be ruled out, our data are consistent with the hypothesis that primordial follicles expressing low levels of K8/K18 are preferentially ablated by follicle attrition, while primordial follicles showing high K8/K18 levels are those predominantly recruited into the growing pool. This suggests that K8/K18 expression could constitute a novel factor regulating primordial follicle...
Source: Human Reproduction - February 1, 2018 Category: Reproduction Medicine Source Type: research
Increased 27-hydroxycholesterol production during luteolysis may mediate the progressive decline in progesterone secretion
This study provides functional evidence of a novel mechanism via increased 27OH synthesis during luteolysis, which subsequently represses progesterone secretion. Increased 27OH may also facilitate the progression of luteolysis in domestic animal species.STUDY FUNDING AND COMPETING INTEREST(S)The authors have nothing to disclose. Support was provided by the Eunice Kennedy Shriver National Institute of Child Health& Human Development (NICHD) of the National Institutes of Health (NIH), award number R00HD067678 to R.L.B.
Source: Molecular Human Reproduction - November 21, 2017 Category: Molecular Biology Source Type: research
hCG activates Epac-Erk1/2 signaling regulating Progesterone Receptor expression and function in human endometrial stromal cells
AbstractSTUDY QUESTIONHow does hCG signal in human endometrial stromal cells (ESCs) and what is its role in regulating ESC function?SUMMARY ANSWERhCG signaling in ESCs activates the extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) pathway through exchange protein activated by cyclic AMP (cAMP) (Epac) and transiently increases progesterone receptor (PR) transcript and protein expression and its transcriptional function.WHAT IS KNOWN ALREADYhCG is one of the earliest embryo-derived secreted signals in the endometrium, which abundantly expresses LH/hCG receptors. hCG signals through cAMP/protein kinase A (PKA) ...
Source: Molecular Human Reproduction - March 28, 2017 Category: Molecular Biology Source Type: research
Spindlin 1 is essential for metaphase II stage maintenance and chromosomal stability in porcine oocytes
This study is based on <span style="font-style:italic;">in vitro</span> investigations with abnormal expression levels of Spin1. This may or may not accurately reflect the situation <span style="font-style:italic;">in vivo</span>.<div class="boxTitle">Wider implications of the findings</div>Spin1 is essential to maintain MII arrest, but a high level of Spin1 induces DNA damage in oocytes and embryos. Thus, a system to accurately regulate Spin1 expression operates in porcine MII-stage oocytes and embryos.<div class="boxTitle">Study funding and competing interest(s)</div>This r...
Source: Molecular Human Reproduction - March 6, 2017 Category: Molecular Biology Source Type: research
