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Azacytidine

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https://www.readbyqxmd.com/read/29050250/teriflunomide-restores-5-azacytidine-sensitivity-via-activation-of-pyrimidine-salvage-in-5-azacytidine-resistant-leukemia-cells
#1
Satoshi Imanishi, Ryoko Takahashi, Seiichiro Katagiri, Chiaki Kobayashi, Tomohiro Umezu, Kazuma Ohyashiki, Junko H Ohyashiki
Previous studies showed that downregulation of pyrimidine salvage underlies resistance against 5-azacytidine (AZA), indicating an important role for de novo pyrimidine synthesis in AZA resistance. Because de novo pyrimidine synthesis is inhibited by the immunomodulator teriflunomide and its pro-drug leflunomide, we examined the effect of combined treatment with AZA and teriflunomide on AZA resistance to develop a novel strategy to cancel and prevent AZA resistance. Teriflunomide markedly inhibited the growth of AZA-resistant human leukemia cell lines (R-U937 and R-HL-60) in comparison with their AZA-sensitive counterparts (U937 and HL-60)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29043987/successful-treatment-of-donor-cell-derived-myelodysplastic-syndrome-with-5-azacytidine
#2
Selim Jennane, Mariyam El Haddad, El Mehdi Mahtat, Kamal Doghmi, Mohammed Mikdame
No abstract text is available yet for this article.
October 18, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/28983843/-azi2-3-utr-is-a-new-slc6a3-downregulator-associated-with-an-epistatic-protection-against-substance-use-disorders
#3
Kefu Liu, Jinlong Yu, Juan Zhao, Yanhong Zhou, Nian Xiong, Jie Xu, Tao Wang, Richard L Bell, Hong Qing, Zhicheng Lin
Regulated activity of SLC6A3, which encodes the human dopamine transporter (DAT), contributes to diseases such as substance abuse disorders (SUDs); however, the exact transcription mechanism remains poorly understood. Here, we used a common genetic variant of the gene, intron 1 DNP1B sequence, as bait to screen and clone a new transcriptional activity, (AZI2)3'UTR, for SLC6A3. (AZI2)3'UTR is a 3' untranslated region (3'UTR) of the human 5-Azacytidine Induced 2 gene (AZI2) but appeared to be transcribed independently of AZI2...
October 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28976612/inherited-thrombocytopenia-caused-by-ankrd26-mutations-misdiagnosed-and-treated-as-myelodysplastic-syndrome-report-on-two-cases
#4
C Zaninetti, V Santini, M Tiniakou, S Barozzi, A Savoia, A Pecci
Thrombocytopenia 2 (THC2) is an autosomal-dominant disorder caused by point substitutions in the 5'UTR of the ANKRD26 gene. Patients have congenital thrombocytopenia, normal platelet morphology and function, and dysmegakaryopoiesis. Thrombocytopenia is frequently discovered only in adulthood and physicians often do not suspect its genetic origin. We describe two unrelated patients referred at two different institutions for investigation of thrombocytopenia. Based on the finding of dysmegakaryopoiesis at bone marrow examination, patients were diagnosed with myelodysplastic syndrome (MDS) (refractory thrombocytopenia) and treated with several courses of 5-azacytidine...
October 4, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28969971/biomimetic-electrical-stimulation-induces-rat-bone-marrow-mesenchymal-stem-cells-to-differentiate-into-cardiomyocyte-like-cells-via-tgf-beta-1-in-vitro
#5
REVIEW
Xueling He, Liang Li, Min Tang, Ye Zeng, Huiming Li, Xiaoqin Yu
Electrical conductance is one of the factors of the microenvironment of cardiomyocytes, and electrical stimulation (ES) has been shown to modulate the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) toward a cardiomyogenic fate. Transforming growth factor-beta 1 (TGF-β1) stimulates the cardiomyogenic marker expression in BMSCs. Herein, we promoted the differentiation of BMSCs into cardiomyocyte-like cells using ES to confirm if TGF-β1 mediates this event in vitro. ES increased protein levels of TGF-β1 in BMSCs, and this effect was better than that observed with 5-azacytidine (5-Aza)...
September 29, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28962638/hypoxia-preconditioning-promotes-cardiac-stem-cell-survival-and-cardiogenic-differentiation-in-vitro-involving-activation-of-the-hif-1%C3%AE-apelin-apj-axis
#6
Jingying Hou, Lei Wang, Huibao Long, Hao Wu, Quanhua Wu, Tingting Zhong, Xuxiang Chen, Changqing Zhou, Tianzhu Guo, Tong Wang
BACKGROUND: Cardiac stem cells (CSCs) transplantation has been regarded as an optimal therapeutic approach for cardiovascular disease. However, inferior survival and low differentiation efficiency of these cells in the local infarct site reduce their therapeutic efficacy. In this study, we investigated the influence of hypoxia preconditioning (HP) on CSCs survival and cardiogenic differentiation in vitro and explored the relevant mechanism. METHODS: CSCs were obtained from Sprague-Dawley rats and cells of the third passage were cultured in vitro and exposed to hypoxia (1% O2)...
September 29, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28956260/expression-and-function-of-hsa-mir-6165-in-human-cell-lines-and-during-the-nt2-cell-neural-differentiation-process
#7
Maryam Hassanlou, Bahram Mohammad Soltani, Seyed Javad Mowla
MicroRNAs are small non-coding RNAs that posttranscriptionally regulate mRNA expression. hsa-miR-6165 which was previously discovered in our group is located in the forth intron of p75NTR gene and its function is still under investigation. As P75NTR has diverse cellular functions, some of the complexity of its function could be attributed to the internally located microRNA. Our analysis revealed that treatment of HCT116 cells with 5-azacytidine promoted differential expression of hsa-miR-6165 from its host gene which is consistent with the bioinformatic prediction of an independent promoter for hsa-miR-6165...
September 27, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28954936/different-schedule-dependent-effects-of-epigenetic-modifiers-on-cytotoxicity-by-anticancer-drugs-in-colorectal-cancer-cells
#8
Mika Hosokawa, Shota Tanaka, Kumiko Ueda, Seigo Iwakawa
Limited information is currently available on how to apply epigenetic modifiers to current colorectal cancer (CRC) chemotherapy. The purpose of this study is to clarify the schedule-dependent effects of combined treatment with conventional anticancer drugs and epigenetic modifiers in human CRC cells. Cytotoxicity in 4 CRC cell lines (SW480, HT29, SW48, and HCT116) was measured using the WST-8 assay. As epigenetic modifiers, 3 DNA methyltransferase (DNMT) inhibitors such as decitabine (DAC), azacytidine (AC), and zebularine (Zeb), and 3 histone deacetylase (HDAC) inhibitors including trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and valproic acid (VPA) were used...
September 28, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28947962/5-azacytidine-promotes-invadopodia-formation-and-tumor-metastasis-through-the-upregulation-of-pi3k-in-ovarian-cancer-cells
#9
Dan Cao, Dan Li, Yong Huang, Yu Ma, Binglan Zhang, Chengjian Zhao, Senyi Deng, Min Luo, Tao Yin, Yu-Quan Wei, Wei Wang
The high incidence of metastasis accounts for most of the lethality of ovarian cancer. Invadopodia are small, specialized types of machinery that degrade the extracellular matrix and are thus involved in the invasion and metastasis of cancer cells. The formation of invadopodia is regulated by both genetic and epigenetic factors. However, the ways by which methylation/demethylation regulates the dynamics of invadopodia in ovarian cancer are largely unknown. In this study, we found that the inhibition of methylation by 5-AZ (5-Azacytidine) increased the formation of invadopodia and enhanced degradation of the extracellular matrix in ovarian cancer cells...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28929261/transplantation-of-mesenchymal-stem-cells-modulated-cx43-and-cx45-expression-in-rats-with-myocardial-infarction
#10
Jin-Yi Li, Hong-Hong Ke, Yan He, Li-Na Wen, Wei-Yan Xu, Zhi-Fu Wu, Yan-Mei Zhao, Guo-Qiang Zhong
At present, little is known about the influence of mesenchymal stem cell (MSC) transplantation on connexin43 (Cx43) and connexin45 (Cx45) remodeling in the ischemic heart. In this study, we investigated the effect of MSC transplantation on Cx43 and Cx45 remodeling in the ischemic heart. Wistar rats were subjected to left anterior descending artery ligation to induce myocardial infarction (MI) and then randomly allocated to receive an intramyocardial injection of PBS (MI group) or 5-azacytidine-induced MSCs (MSCs group)...
September 19, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28916527/demethylation-therapy-as-a-targeted-treatment-for-human-papilloma-virus-associated-head-and-neck-cancer
#11
Asel K Biktasova, Michael Hajek, Andrew B Sewell, Cyril S Gary, Gary Bellinger, Hari Deshpande, Aarti K Bhatia, Barbara A Burtness, Benjamin L Judson, Saral Mehra, Wendell G Yarbrough, Natalia Issaeva
PURPOSE: DNA methylation in human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) may have importance for continuous expression of HPV oncogenes, tumor cell proliferation and survival. Here, we determined activity of a global DNA demethylating agent, 5-azacytidine (5-aza), against HPV+ HNSCC in pre-clinical models and explored it as a targeted therapy in a window trial enrolling patients with HPV+ HNSCC. EXPERIMENTAL DESIGN: Sensitivity of HNSCC cells to 5-aza treatment was determined, then 5-aza activity was tested in vivo using xenografted tumors in a mouse model...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28901815/high-grade-b-cell-lymphoma-of-the-peritoneum-as-a-result-of-transformation-of-a-cd5-negative-monoclonal-b-lymphocytosis-population-in-a-patient-with-myelodysplastic-syndrome-treated-with-5-azacytidine
#12
Maria Dimou, Maria Roumelioti, Aglaia Dimitrakopoulou, Catherin Bitsani, Sotiria Kotsanti, Panayiota Petsa, Paraskevi Papaioannou, Marie-Christine Kyrtsonis, Panayiotis Panayiotidis
No abstract text is available yet for this article.
September 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28901456/the-antitumor-effects-of-arsenic-trioxide-in-mantle-cell-lymphoma-via-targeting-wnt-%C3%AE-%C3%A2-catenin-pathway-and-dna-methyltransferase-1
#13
Xin-Yu Li, Ying Li, Lingyan Zhang, Xin Liu, Lili Feng, Xin Wang
Mantle cell lymphoma (MCL) is an aggressive non‑Hodgkin lymphoma (NHL) with poor prognosis. The rapid progression and frequently relapse make it urgent to identify therapeutic agents with potent antitumor effect. Increasing evidence indicated that dysregulation of Wnt/β‑catenin pathway and abnormal methylation appeared to promote tumorigenesis. Arsenic trioxide (As2O3, ATO) has been reported effective in many hematologic malignancies in recent studies, however, the mechanism and effects of ATO in MCL still need further research...
November 2017: Oncology Reports
https://www.readbyqxmd.com/read/28885352/successful-5-azacytidine-treatment-of-myeloid-sarcoma-and-leukemia-cutis-associated-with-myelodysplastic-syndrome-a-case-report-and-literature-review
#14
REVIEW
Takayuki Katagiri, Takashi Ushiki, Masayoshi Masuko, Tomoyuki Tanaka, Shukuko Miyakoshi, Kyoko Fuse, Yasuhiko Shibasaki, Jun Takizawa, Sadao Aoki, Hirohito Sone
RATIONALE: Myeloid sarcoma (MS) and leukemia cutis (LC) are extramedullary tumors comprising myeloid blasts. They can occur de novo or concurrently with hematological disorders, usually acute myeloid leukemia (AML). AML chemotherapy is generally the initial therapy for MS and LC, and hematopoietic stem cell transplantation (HSCT) can be considered as additional therapy. However, treatment for older patients who are unable to continue intensive chemotherapy is not currently standardized...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28881739/a-phase-i-trial-of-azacitidine-and-nanoparticle-albumin-bound-paclitaxel-in-patients-with-advanced-or-metastatic-solid-tumors
#15
Adam L Cohen, Abhijit Ray, Matthew Van Brocklin, David M Burnett, Randy C Bowen, Donna L Dyess, Thomas W Butler, Theresa Dumlao, Hung T Khong
BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein, is downregulated by hypermethylation in many cancers. Hypomethylating agents such as azacitidine can upregulate SPARC in tumors, which may enhance the accumulation of albumin-bound drugs at tumor site. The objectives of this phase I trial was to determine the safety and maximum tolerated dose and to assess any clinical activity of the combination of azacytidine and weekly nanoparticle-albumin-bound (nab®) paclitaxel...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28859077/distinct-roles-and-differential-expression-levels-of-wnt5a-mrna-isoforms-in-colorectal-cancer-cells
#16
Tsui-Chin Huang, Pin-Tse Lee, Ming-Heng Wu, Chi-Chen Huang, Chiung-Yuan Ko, Yi-Chao Lee, Ding-Yen Lin, Ya-Wen Cheng, Kuen-Haur Lee
The canonical Wnt/β-catenin pathway is constitutively activated in more than 90% of colorectal cancer (CRC) cases in which β-catenin contributes to CRC cell growth and survival. In contrast to the Wnt/β-catenin pathway, the non-canonical Wnt pathway can antagonize functions of the canonical Wnt/β-catenin pathway. Wnt5a is a key factor in the non-canonical Wnt pathway, and it plays diverse roles in different types of cancers. It was shown that reintroducing Wnt5a into CRC cells resulted in inhibited cell proliferation and impaired cell motility...
2017: PloS One
https://www.readbyqxmd.com/read/28846166/cortisol-inhibits-csf2-and-csf3-via-dna-methylation-and-inhibits-invasion-in-first-trimester-trophoblast-cells
#17
Arianna Smith, Elizabeth Witte, Devin McGee, Jason Knott, Kavita Narang, Karen Racicot
PROBLEM: Heightened maternal stress affects trophoblast function and increases risk for adverse pregnancy outcomes. METHODS OF STUDY: Studies were performed using the first-trimester trophoblast cell line, Sw.71. Cytokines were quantified using qPCR and ELISA. Epigenetic regulation of cytokines was characterized by inhibiting histone deacetylation (1 μmol/L suberoylanilide hydroxamic acid [SAHA]) or methylation (5 μmol/L 5-azacytidine), or with chromatin immunoprecipitation (ChIP) with a pan-acetyl histone-3 antibody...
August 28, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28831600/encouraging-results-with-the-compassionate-use-of-hydralazine-valproate-transkrip%C3%A2-as-epigenetic-treatment-for-myelodysplastic-syndrome-mds
#18
Myrna Candelaria, Sebastian Burgos, Mayra Ponce, Ramiro Espinoza, Alfonso Dueñas-Gonzalez
The hypomethylating agents azacytidine and decitabine are unaffordable for many patients with MDS. The combination of the DNA methyltransferase inhibitor hydralazine and the histone deacetylase inhibitor valproate has shown preliminary efficacy in MDS. The aim of this study is to evaluate the clinical efficacy and safety of hydralazine/valproate in a case series of MDS patients treated in a compassionate manner. Hydralazine was dosed according to the acetylation genotype of patients (slow acetylators 83 mg daily; fast acetylators 182 mg daily), and valproate was dosed at 30 mg/kg/day...
August 23, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28821633/cell-autonomous-cytotoxicity-of-type-i-interferon-response-via-induction-of-endoplasmic-reticulum-stress
#19
Chrysovalantou Mihailidou, Athanasios G Papavassiliou, Hippokratis Kiaris
The interaction of IFN with specific membrane receptors that transduce death-inducing signals is considered to be the principle mechanism of IFN-induced cytotoxicity. In this study, the classic non-cell-autonomous cytotoxicity of IFN was augmented by cell-autonomous mechanisms that operated independently of the interaction of IFN with its receptors. Cells primed to produce IFN by 5-azacytidine (5-aza) underwent endoplasmic reticulum (ER) stress. The chemical chaperones tauroursodeoxycholate (TUDCA) and 4-phenylbutyrate (4-PBA), as well as the iron chelator ciclopirox (CPX), which reduces ER stress, alleviated the cytotoxicity of 5-aza...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28791409/pcdh9-acts-as-a-tumor-suppressor-inducing-tumor-cell-arrest-at-g0-g1-phase-and-is-frequently-methylated-in-hepatocellular-carcinoma
#20
Jun Lv, Pengfei Zhu, Xiaolei Zhang, Ling Zhang, Xiangmei Chen, Fengmin Lu, Zujiang Yu, Shuang Liu
Tumor suppressor genes (TSGs) are frequently involved in the pathogenesis of hepatocellular carcinoma (HCC). The epigenetic and genetic alterations of a novel TSG‑protocadherin 9 (PCDH9) and its functions in the pathogenesis of HCC were investigated. The methylation status of the PCDH9 promoter was quantitatively analyzed, and the PCDH9 expression was analyzed in HCC cell lines treated with 5‑azacytidine. The effects of PCDH9 re‑expression and knockdown on growth, proliferation and tumorigenic potential were determined...
October 2017: Molecular Medicine Reports
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