Publications by authors named "Kumiko Ohta"
Article Synopsis
- Differentiation therapy shows potential for treating acute myeloid leukemia (AML), but effective methods that work across different AML subtypes are needed.
- The study reveals that inhibiting a specific regulatory element of FOXO genes can induce differentiation in AML cells, identifying TRIB1 as a key gene that keeps these cells undifferentiated.
- A new therapeutic approach combining a DNA-binding inhibitor with a chemotherapy drug effectively reduced TRIB1 levels, leading to AML cell differentiation and inhibiting tumor growth in animal models without significant side effects.
Article Synopsis
- Stem cell self-renewal is essential for maintaining tissue health, and its disruption can lead to serious health issues like organ failure or cancer.
- A study found that Spred1 helps regulate hematopoietic stem cell (HSC) self-renewal under high-fat diet conditions, preventing issues related to stem cell failure.
- When Spred1 is absent, the resulting HSC dysfunction can lead to severe blood-related diseases, with diet and changes in gut microbiota playing a significant role in these disruptions.
Although abnormal metabolic regulation is a critical determinant of cancer cell behavior, it is still unclear how an altered balance between ATP production and consumption contributes to malignancy. Here we show that disruption of this energy balance efficiently suppresses aggressive malignant gliomas driven by mammalian target of rapamycin complex 1 (mTORC1) hyperactivation. In a mouse glioma model, mTORC1 hyperactivation induced by conditional Tsc1 deletion increased numbers of glioma-initiating cells (GICs) in vitro and in vivo Metabolic analysis revealed that mTORC1 hyperactivation enhanced mitochondrial biogenesis, as evidenced by elevations in oxygen consumption rate and ATP production.
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- - JBIR-141 and JBIR-142 are identified as strong inhibitors of the Foxo3a protein, featuring three distinct chemical substructures derived from amino acid residues and other complex components.
- - The absolute configurations of these compounds were established through various analysis techniques including spectroscopy and LC-MS.
- - The potency of these compounds is highlighted by their ability to inhibit Foxo3a transcriptional activity, with IC50 values of 23.1 nM for JBIR-141 and 166.2 nM for JBIR-142.
The Notch signal regulates both cell viability and apoptosis, and maintains stemness of various cancers including glioblastoma (GBM). Although Notch signal inhibition may be an effective strategy in treating GBM initiating cells (GICs), its applicability to the different subtypes of GBM remains unclear. Here, we analyzed the effectiveness of MRK003, a preclinical γ-secretase inhibitor, on GICs.
View Article and Find Full Text PDFAcute myeloid leukaemia (AML) is a heterogeneous neoplastic disorder in which a subset of cells function as leukaemia-initiating cells (LICs). In this study, we prospectively evaluated the leukaemia-initiating capacity of AML cells fractionated according to the expression of a nucleolar GTP binding protein, nucleostemin (NS). To monitor NS expression in living AML cells, we generated a mouse AML model in which green fluorescent protein (GFP) is expressed under the control of a region of the NS promoter (NS-GFP).
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- Glioblastomas often have genetic changes that increase the activity of mTORC1, particularly involving the loss of TSC1 or TSC2, crucial regulators of mTORC1.
- In experiments with mice, Tsc1 deficiency was found to increase mTORC1 activity but hinder the self-renewal of neural stem/progenitor cells, suggesting that Tsc1 is important for their growth.
- While Tsc1 loss alone didn’t cause gliomas, in the presence of an active EGFR mutant, it led to faster glioma development and more severe tumor characteristics, indicating that mTORC1's activity accentuates tumor growth when coupled with other genetic mutations.
Article Synopsis
- - Nucleostemin (NS) is a protein found in the nucleolus that plays a key role in making ribosomes and protecting telomeres, with its expression notably high in undifferentiated human testicular germ cell tumors.
- - In mouse models, cells expressing high levels of NS were shown to actively proliferate and possess traits typical of tumor-initiating cells, aided by increased GTP levels that support NS stability.
- - The loss of NS expression due to OCT3/4 deficiency led to slower tumor growth and the loss of undifferentiated characteristics in teratomas, highlighting NS's critical role in maintaining the properties and growth of germ cell tumors.
Article Synopsis
- The study explores the roles of Chk1 and Chk2 kinases in cancer, indicating that while they're linked to cancer signaling, they don't appear to increase cancer risk on their own in mice.
- However, when both Chk1 and Chk2 are altered, as in certain double-mutant mice, they show a tendency toward cancer due to compromised checkpoint functions during cell division and DNA repair.
- The findings reveal that these double-mutant mice experience more spontaneous DNA damage and elevated p53 levels, but they are unable to effectively respond to additional DNA damage, which could contribute to a higher cancer risk.
Article Synopsis
- * In contrast, MOZ, another acetyltransferase, is increased during this process, despite not being rearranged in liver tissues with hyperplastic nodules.
- * MOZ enhances the activity of the GSTP promoter through the GPE1 enhancer and collaborates with the Nrf2-MafK heterodimer, leading to elevated GSTP expression, which is significant in early stages of liver cancer.
This study was conducted to explore the relationship between physicochemical property and toxic effectiveness using rat red blood cells (RBCs). The toxic effectiveness of acid nonsteroidal anti-inflammatory drugs (NSAIDs) was systemically examined by the depletion of intracorpuscular adenosine triphosphate (ATP), glutathione (GSH), and hemoglobin (Hb) at various doses, increased every 5 fmol/RBC. When the RBCs were incubated with NSAIDs, the drugs attained maximum levels within RBC, and the levels were then reduced.
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- This study investigates how aspirin (ASP) and indomethacin (IND) interact on a pharmacokinetic level using rat blood cells (RBCs) and liver cells (hepatocytes).
- In RBCs, aspirin and its breakdown product, salicylic acid (SA), increase indomethacin concentration while promoting its hydrolysis.
- In hepatocytes, low doses of IND are mainly glucuronidated (a type of metabolism), and the presence of ASP/SA inhibits this process, while higher doses lead to increased hydrolysis, suggesting that aspirin affects how indomethacin is processed and eliminated in the body.