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  1. Article ; Online: Efficacy and tolerability of a modified pediatric-inspired intensive regimen for acute lymphoblastic leukemia in older adults.

    Patel, Anand Ashwin / Heng, Joseph / Dworkin, Emily / Monick, Sarah / Derman, Benjamin A / DuVall, Adam S / Gurbuxani, Sandeep / Kosuri, Satyajit / Liu, Hongtao / Thirman, Michael / Godley, Lucy A / Odenike, Olatoyosi / Larson, Richard A / Stock, Wendy

    EJHaem

    2021  Volume 2, Issue 3, Page(s) 413–420

    Abstract: Although acute lymphoblastic leukemia (ALL) is most common in pediatric and adolescent and young adult (AYA) patients, 20% of cases are diagnosed in patients ≥ 55 years old. Use of intensive pediatric regimens in AYA populations has demonstrated ... ...

    Abstract Although acute lymphoblastic leukemia (ALL) is most common in pediatric and adolescent and young adult (AYA) patients, 20% of cases are diagnosed in patients ≥ 55 years old. Use of intensive pediatric regimens in AYA populations has demonstrated excellent tolerability and significant improvements in event-free survival (EFS) and overall survival (OS). The backbone of pediatric regimens includes asparaginase and corticosteroids, both of which are associated with more toxicity in older patients and those with body mass index (BMI) ≥ 30 kg/m which leads to poor tolerance of these regimens. We tested the safety and efficacy of a dose-modified The Cancer and Leukemia Group B 10403 regimen using reduced doses of pegylated (PEG)-asparaginase (ASP) and corticosteroids (RD-10403) in 30 patients with Philadelphia-chromosome negative ALL who were ≥50-year-old and younger adults with significant metabolic or hepatic co-morbidities. The complete remission rate on day 28 was 77%, 3-year EFS was 54%, and estimated 3-year OS was 55%. Grade 3+ toxicity was noted in 40% of patients during induction, and induction-related mortality was 3%. Additional prospective evaluation of RD-10403 is merited to determine efficacy and safety of this regimen and to serve as a framework for chemoimmunotherapy combination therapy.
    Language English
    Publishing date 2021-06-22
    Publishing country United States
    Document type Journal Article
    ISSN 2688-6146
    ISSN (online) 2688-6146
    DOI 10.1002/jha2.224
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A Phenotypic Switch of Differentiated Glial Cells to Dedifferentiated Cells Is Regulated by Folate Receptor α.

    Monick, Sarah / Mohanty, Vineet / Khan, Mariam / Yerneni, Gowtham / Kumar, Raj / Cantu, Jorge / Ichi, Shunsuke / Xi, Guifa / Singh, Bal Ram / Tomita, Tadanori / Mayanil, Chandra Shekhar

    Stem cells (Dayton, Ohio)

    2019  Volume 37, Issue 11, Page(s) 1441–1454

    Abstract: In a previous study, we showed that folate receptor-α (FRα) translocates to the nucleus where it acts as a transcription factor and upregulates Hes1, Oct4, Sox2, and Klf4 genes responsible for pluripotency. Here, we show that acetylation and ... ...

    Abstract In a previous study, we showed that folate receptor-α (FRα) translocates to the nucleus where it acts as a transcription factor and upregulates Hes1, Oct4, Sox2, and Klf4 genes responsible for pluripotency. Here, we show that acetylation and phosphorylation of FRα favor its nuclear translocation in the presence of folate and can cause a phenotypic switch from differentiated glial cells to dedifferentiated cells. shRNA-FRα mediated knockdown of FRα was used to confirm the role of FRα in dedifferentiation. Ocimum sanctum hydrophilic fraction-1 treatment not only blocks the folate mediated dedifferentiation of glial cells but also promotes redifferentiation of dedifferentiated glial cells, possibly by reducing the nuclear translocation of ~38 kDa FRα and subsequent interaction with chromatin assembly factor-1. Stem Cells 2019;37:1441-1454.
    MeSH term(s) Cell Dedifferentiation/drug effects ; Cell Dedifferentiation/genetics ; Cell Line ; Cell Line, Tumor ; Folate Receptor 1/genetics ; Folate Receptor 1/metabolism ; Folic Acid/analogs & derivatives ; Folic Acid/pharmacology ; Humans ; Neural Crest/drug effects ; Neural Crest/metabolism ; Neuroglia/drug effects ; Neuroglia/metabolism ; Nuclear Transfer Techniques ; Ocimum sanctum/chemistry ; Octamer Transcription Factor-3/metabolism ; RNA, Small Interfering/genetics ; SOXB1 Transcription Factors/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances CNOT8 protein, human ; Folate Receptor 1 ; Octamer Transcription Factor-3 ; POU5F1 protein, human ; RNA, Small Interfering ; SOXB1 Transcription Factors ; Transcription Factors ; 5,11-methenyltetrahydrohomofolate (77921-44-9) ; Folic Acid (935E97BOY8)
    Language English
    Publishing date 2019-08-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1143556-2
    ISSN 1549-4918 ; 1066-5099
    ISSN (online) 1549-4918
    ISSN 1066-5099
    DOI 10.1002/stem.3067
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Folate Receptor Alpha Upregulates Oct4, Sox2 and Klf4 and Downregulates miR-138 and miR-let-7 in Cranial Neural Crest Cells.

    Mohanty, Vineet / Shah, Amar / Allender, Elise / Siddiqui, M Rizwan / Monick, Sarah / Ichi, Shunsuke / Mania-Farnell, Barbara / G McLone, David / Tomita, Tadanori / Mayanil, Chandra Shekhar

    Stem cells (Dayton, Ohio)

    2016  Volume 34, Issue 11, Page(s) 2721–2732

    Abstract: Prenatal folic acid (FA) supplementation prevents neural tube defects. Folate receptor alpha (FRα) is critical for embryonic development, including neural crest (NC) development. Previously we showed that FRα translocates to the nucleus in response to FA, ...

    Abstract Prenatal folic acid (FA) supplementation prevents neural tube defects. Folate receptor alpha (FRα) is critical for embryonic development, including neural crest (NC) development. Previously we showed that FRα translocates to the nucleus in response to FA, where it acts as a transcription factor. In this study, we examined if FA through interaction with FRα regulates stem cell characteristics of cranial neural crest cells (CNCCs)-critical for normal development. We hypothesized that FRα upregulates coding genes and simultaneously downregulates non-coding miRNA which targets coding genes in CNCCs. Quantitative RT-PCR and chromatin immunoprecipitation showed that FRα upregulates Oct4, Sox2, and Klf4 by binding to their cis-regulator elements-5' enhancer/promoters defined by H3K27Ac and p300 occupancy. FA via FRα downregulates miRNAs, miR-138 and miR-let-7, which target Oct4 and Trim71 (an Oct4 downstream effector), respectively. Co-immunoprecipitation data suggests that FRα interacts with the Drosha-DGCR8 complex to affect pre-miRNA processing. Transfecting anti-miR-138 or anti-miR-let-7 into non-proliferating neural crest cells (NCCs) derived from Splotch (Sp
    Language English
    Publishing date 2016-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1143556-2
    ISSN 1549-4918 ; 1066-5099
    ISSN (online) 1549-4918
    ISSN 1066-5099
    DOI 10.1002/stem.2421
    Database MEDical Literature Analysis and Retrieval System OnLINE

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