Publications by authors named "Sho Ikeda"
Basic research to expand treatment options for multiple myeloma is greatly needed due to the refractory nature of the disease. Histone deacetylase (HDAC) inhibitors, which are epigenetic regulators, are attractive but have limited applications. MicroRNAs (miRNAs), which are also epigenetic regulators, are important molecules that may lead to future therapeutic breakthroughs.
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- * A study of 126 Japanese patients using wKd therapy showed an overall response rate of 66.3% and a median progression-free survival of 9.5 months.
- * The study also reported that treatment-emergent adverse events occurred in 45.8% of patients, with 20.8% experiencing severe (grade ≥3) events, but no new safety concerns were identified.
The patient was a 21-year-old man who had been diagnosed with Crohn's disease and received infliximab and azathioprine six years earlier. He was admitted with fever and fatigue. Peripheral blood examination showed LDH 2,473 U/l and thrombocytopenia, and contrast-enhanced computed tomography (CT) showed hepatosplenomegaly.
View Article and Find Full Text PDFIntroduction The overall survival (OS) of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) has improved with the combination of tyrosine kinase inhibitor (TKI) with intensive chemotherapy. In recent years, there has been increased interest in the possibility of long-term survival without allogeneic hematopoietic stem cell transplantation (HSCT) or maintenance therapy. The aim of this study was to determine the effectiveness of treatment and the resultant outcomes in Ph+ALL patients using real-world data.
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- * Unfortunately, she experienced a relapse 150 days after the transplant, prompting treatment with venetoclax and azacitidine as a last-resort option.
- * Despite this salvage therapy, the patient ultimately succumbed to the disease, highlighting the poor prognosis associated with this type of AML and the urgent need for new treatment strategies.
Background: The immunomodulatory drug lenalidomide, which is now widely used for the treatment of multiple myeloma (MM), exerts pharmacological action through the ubiquitin-dependent degradation of IKZF1 and subsequent down-regulation of interferon regulatory factor 4 (IRF4), a critical factor for the survival of MM cells. IKZF1 acts principally as a tumour suppressor via transcriptional repression of oncogenes in normal lymphoid lineages. In contrast, IKZF1 activates IRF4 and other oncogenes in MM cells, suggesting the involvement of unknown co-factors in switching the IKZF1 complex from a transcriptional repressor to an activator.
View Article and Find Full Text PDFBackground: Multiple myeloma (MM) is a hematopoietic malignancy for which proteasome inhibitors have become available in recent years. However, many patients develop resistance to these drugs during treatment. Therefore, it is important to elucidate the mechanisms underlying resistance acquisition by proteasome inhibitors.
View Article and Find Full Text PDFExtramedullary disease (EMD) is known to be associated with chemoresistance and poor prognosis in multiple myeloma (MM); however, the mechanisms of its development are not fully understood. Elucidating the mechanism of EMD development and its therapeutic targeting would greatly contribute to further improvement of treatment outcome in patients with MM. Here, we show that bone marrow stroma cell-derived hyaluronan (HA) elicits homophilic interactions of MM cells by binding to surface CD44, especially long-stretch variants, under physiological shear stress and generates cell clusters that might develop into EMD.
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- Anionic stitching polymerization creates a novel type of polymer made from styryl(vinyl)silanes, featuring fused sila-bicyclic structures in its main chain.* -
- The resulting polymers exhibit good thermal stability and high glass-transition temperatures, making them suitable for various applications.* -
- These polymers are also highly transparent in the visible light spectrum, enhancing their potential uses in optics and materials science.*
Article Synopsis
- Certain microRNAs (miRNAs), including miR-26, influence lymphoma development, and our study focused on understanding miR-26's role in cutaneous T-cell lymphoma (CTCL).
- We found that miR-26 is significantly altered in CTCL cells and that its presence extends survival in mice, indicating its potential as a tumor suppressor.
- Our research suggests that miR-26 regulates the IL-22-STAT3-CCL20 pathway, with IL-22 knockdown leading to reduced tumor invasion and potential for new therapies targeting IL-22 in advanced CTCL.
Article Synopsis
- Researchers developed a new method using rhodium as a catalyst to create silicon-bridged π-conjugated polymers from alkynylsilylacetylenes, which are easier to make and not currently accessible through existing methods.
- The polymerization can incorporate various types of alkynes (like diynes, triynes, and tetraynes) to produce these unique polymers.
- The solubility of these polymers can be fine-tuned by adding specific functional groups to the silicon atoms, and further modifications can be made to create varied polyacetylenes by removing silicon groups.
Article Synopsis
- * Recent advancements in targeted therapies have improved the prognosis for MM patients, but almost all experience disease progression due to treatment resistance influenced by the bone marrow microenvironment.
- * Hypoxia (low oxygen levels) in the bone marrow leads to changes that help myeloma cells survive by shifting from reliance on IRF4 and MYC to using hypoxia-inducible factors (HIFs), suggesting that combining treatments targeting these pathways could enhance remission outcomes.
Article Synopsis
- Retropharyngeal abscess is a serious condition that can lead to significant health issues if not recognized early, particularly in young children like the 10-month-old girl discussed in the case.
- Despite initial treatment with surgery and antibiotics, the girl's neck abscesses recurred, prompting a change in medication to successfully control the infection without further surgery.
- The absence of immune function abnormalities indicates that even healthy individuals can develop severe neck infections, highlighting the need for careful evaluation of cervical abscesses in pediatric patients.
Article Synopsis
- * Patients with the translocation t(11;14) and B-cell-associated gene expression showed reduced sensitivity to daratumumab but heightened sensitivity to the BCL2 inhibitor venetoclax, suggesting a complex relationship between cell maturity and treatment response.
- * The study emphasizes the need to consider both CD38 expression and cell differentiation stages when developing treatment strategies for multiple myeloma, especially in patients with specific genetic markers.
[Identification of hypoxia-specific therapeutic targets in multiple myeloma].
Rinsho Ketsueki
May 2021
The bone marrow microenvironment is low in oxygen, promoting a hypoxic response which causes myeloma cells to acquire stem cell properties and enhanced therapy resistance. We performed comprehensive gene and microRNA expression analyses of samples from myeloma patients and cell lines cultured under hypoxia. Through this, we identified the histone demethylase KDM3A, the glycolytic enzyme HK2, and microRNA-210 as factors playing important roles in the behavior of cells under hypoxic conditions.
View Article and Find Full Text PDFMultiple myeloma (MM) is an incurable hematopoietic neoplasm derived from plasma cells, and existing in the bone marrow. Recent developments in the field of myeloma onco-biology have enabled the use of proteasome inhibitors (PIs) as key drugs for MM. PIs can increase cell sensitivity to endoplasmic reticulum stress, leading to apoptosis of myeloma cells.
View Article and Find Full Text PDFWe report a case of a 74-year-old man with a cluster of differentiation (CD) 7-positive diffuse large B-cell lymphoma (DLBCL) in the right nasal cavity. Flow cytometry analyses showed CD7 and CD20 positivity in tumor cells. The patient received 6 cycles of R-CHOP plus local radiation therapy because positron emission tomography-computed tomography after R-CHOP revealed an intranasal lesion.
View Article and Find Full Text PDFA 72-year-old man presented with a 6-month history of systemic edema. Hyperpigmentation, hemangioma, pleural effusion, IgG-kappa-type monoclonal protein, high vascular endothelial growth factor values, renal failure, and nerve conduction study abnormalities were also present. Multiparameter flow cytometry (MFC) showed 0.
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- Researchers created a DCL2&4-double knockdown tomato plant line (72E) to study RNA silencing and its impact on plant defenses against the potato spindle tuber viroid (PSTVd).
- The 72E line showed increased PSTVd accumulation and developed harmful necrosis due to decreased levels of small RNAs that typically mitigate viroid effects.
- High levels of reactive oxygen species (ROS) were linked to the insufficient DCL activity in the 72E plants, which impaired the regulation of detoxifying enzymes, leading to the severe symptoms observed.
Article Synopsis
- This study explores the impact of false-negative F-FDG PET/CT results in patients with multiple myeloma (MM), particularly those with low expression of hexokinase-2 (HK2), which may influence diagnosis and treatment outcomes.
- Researchers analyzed 90 newly diagnosed MM patients during induction therapy and categorized them based on PET/CT and diffusion-weighted MRI results, identifying a group with false-negative PET/CT results.
- Findings revealed that patients with false-negative PET/CT had better prognosis indicators, such as longer time to next treatment and progression-free survival, suggesting that low HK2 expression might indicate lower disease risk despite misleading PET/CT results.
Rhodium-Catalyzed Stitching Polymerization of 1,5-Hexadiynes and Related Oligoalkynes.
Angew Chem Int Ed Engl
April 2019
Article Synopsis
- - A new polymerization method called rhodium-catalyzed stitching polymerization has been created to synthesize π-conjugated polymers, using nonconjugated 1,5-hexadiynes as monomers.
- - This polymerization technique is efficient, operates under mild conditions, and can also work with other similar monomers like 1,5,9-decatriyne and 1,5,9,13-tetradecatetrayne.
- - The method is advantageous because it allows the creation of difficult-to-make repeating units without needing a preformed bridged π-conjugated monomer.
The thermal properties of micron scale particles are an important factor in the design of composite materials and other applications. Here we present an optical technique based on frequency domain thermoreflectance (FDTR) that is capable of measuring the thermal conductivity of individual particles a few microns across. In addition, the technique can provide values for a particle's effective volume which is a new capability compared to conventional FDTR applied to multilayer samples.
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- This study evaluated the safety and efficacy of a lenalidomide and dexamethasone combo therapy in elderly Japanese patients with newly diagnosed multiple myeloma.
- Of the 40 patients, the overall response rate was 68.6%, with a 2-year survival rate of 88.5%, though safety did not correlate with lenalidomide plasma levels.
- Higher plasma concentrations of lenalidomide were linked to increased severe adverse events, suggesting that monitoring levels could help manage treatment toxicity.
Article Synopsis
- * The study identifies that under hypoxia, the gene KDM3A is significantly upregulated, which helps myeloma cells avoid apoptosis (cell death) by increasing glycolytic gene expression through HIF-1α.
- * Targeting the hypoxia-driven pathway involving HIF-1α, KDM3A, and the noncoding gene MALAT1 may offer new therapeutic strategies to treat myeloma cells resistant to current therapies.