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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

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

Targeting Oncoprotein Translation with Rocaglates in MYC-Driven Lymphoma
Background: c-MYC (MYC) is commonly dysregulated in aggressive B cell lymphomas. MYC associated lymphoma, especially Double Hit lymphoma (DHL) and Double-Expression Lymphoma (DEL) which are characterized by MYC and BCL2 dual overexpression usually present with the inferior outcome as rapid disease progression and poor response to standard chemotherapy regimen. Nevertheless, MYC is considered as an "undruggable" target and targeting strategies such as suppressing MYC transcription by bromodomain (BRD)-4 inhibitors have been widely investigated in both preclinical models and clinical trials. However, increasing evidence has ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, X., Bi, C., Lu, T., Yue, T., Zhang, W., Zhang, X., Cheng, W., Tian, T., Lunning, M. A., Vose, J. M., Pelletier, J., Porco, J. A., Tao, J., Fu, K. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents: Specific Pathway Inhibitors Source Type: research

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

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

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

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

Gene Therapy Leaves a Vicious Cycle
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - April 23, 2019 Category: Cancer & Oncology Source Type: research

FKN Facilitates HK-2 Cell EMT and Tubulointerstitial Lesions via the Wnt/ β-Catenin Pathway in a Murine Model of Lupus Nephritis
In this study, we therefore examined whether FKN could stimulate the process of EMT, NF-kB, TGFβ, CCL22, F4/80, inflammation, and tubulointerstitial fibrosis in a murine model of LN. We also determined whether FKN was involved in the EMT process of Wnt/β-catenin-expressing HK-2 cells. Mechanistically, we ascertained, for the first time, whether FKN up-regulated EMT-related gene signatures (e.g., vimentin, α-SMA), and hence, renal tubulointerstitial fibrogenesis, and the role of the Wnt/β-catenin signaling pathway in this process. Materials and Methods Cell Culture, Stable Infection, and Gr...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Osteoprotegerin interacts with syndecan-1 to promote human endometrial stromal decidualization by decreasing Akt phosphorylation
In this study, based on a number of approaches, it was demonstrated that OPG mediated the repression of Akt that occurs during human stromal cell decidualization, however, the molecular link between OPG and Akt signaling was not determined, and still requires further exploration.WIDER IMPLICATIONS OF THE FINDINGSOPG is required for decidualization, and a decrease in OPG levels is associated with RPL. These findings provide a new candidate molecule for the diagnosis and potential treatment of RPL.STUDY FUNDING/COMPETING INTEREST(S)This work was supported in part by the National Natural Science Foundation of China U1605223 (...
Source: Human Reproduction - October 13, 2020 Category: Reproduction Medicine Source Type: research

Bioinformatics analyses show dysregulation of calcium-related genes in Angelman syndrome mouse model.
Abstract BACKGROUND: Angelman syndrome (AS) is a genetic neurodevelopmental disorder caused by the loss of function of the UBE3A protein in the brain. In a previous study, we showed that activity-dependent calcium dynamics in hippocampal CA1 pyramidal neurons of AS mice is compromised, and its normalization rescues the hippocampal-dependent deficits. Therefore, we expected that the expression profiles of calcium-related genes would be altered in AS mice hippocampi. METHODS: We analyzed mRNA sequencing data from AS model mice and WT controls in light of the newly published CaGeDB database of calcium-related ge...
Source: Neurobiology of Disease - November 16, 2020 Category: Neurology Authors: Panov J, Kaphzan H Tags: Neurobiol Dis Source Type: research

Erastin induces ferroptosis via ferroportin-mediated iron accumulation in endometriosis
This study was mainly conducted in primary human endometrial stromal cells. Therefore, the function of FPNin vivo need to be further investigated.WIDER IMPLICATIONS OF THE FINDINGSOur findings reveal that erastin may serve as a potential therapeutic treatment for endometriosis.STUDY FUNDING/COMPETING INTEREST(S)This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. The authors declare no conflict of interest.
Source: Human Reproduction - December 30, 2020 Category: Reproduction Medicine Source Type: research