Publications by authors named "Osumi T"

Background: The E-cadherin, α- and β-Catenin interaction at the cell adherens junction plays a key role in cell adhesion; alteration in the expression and function of these genes are associated with disease progression in several solid tumors including prostate cancer. The membranous β-Catenin is dynamically linked to the cellular cytoskeleton through interaction with α-Catenin at amino acid positions threonine 120 (T120) to 151 of β-Catenin. Nuclear presence of α-Catenin modulates the sensitivity of cells to DNA damage.

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  • Chronic graft-versus-host disease (cGVHD) is a significant complication following stem cell transplants, often leading to poor outcomes for patients, especially after steroid treatments fail.
  • A study in Japan examined the use of ibrutinib for treating patients with steroid-dependent or refractory cGVHD and showed promising results, with an overall response rate of 84.2%.
  • Patients experienced improvements in various affected organs and reduced corticosteroid dependency, indicating ibrutinib's potential as an effective treatment for cGVHD.
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Background: The benefit of adding rituximab to standard lymphomes malins B (LMB) chemotherapy for children with high-risk mature B-cell non-Hodgkin lymphoma (B-NHL) has previously been demonstrated in an international randomized phase III trial, to which the Japanese Pediatric Leukemia/Lymphoma Study Group could not participate.

Methods: To evaluate the efficacy and safety of rituximab in combination with LMB chemotherapy in Japanese patients, we conducted a single-arm multicenter trial.

Results: In this study, 45 patients were enrolled between April 2016 and September 2018.

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Background: Like its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an acceptable quality of life. A potential intervention is modulation of the composition of gut microbiota, and in fact, probiotic treatment has been proposed and tried in human atopic dermatitis (AD) patients. Since dogs are currently receiving intensive medical care, this will be the same option for dogs, while evidence of gut dysbiosis in cAD is still missing, although skin microbial profiling in cAD has been conducted in several studies.

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Bromodomains (BD) are epigenetic readers of histone acetylation involved in chromatin remodeling and transcriptional regulation of several genes including protooncogene cellular myelocytomatosis (c-Myc). c-Myc is difficult to target directly by agents due to its disordered alpha helical protein structure and predominant nuclear localization. The epigenetic targeting of c-Myc by BD inhibitors is an attractive therapeutic strategy for prostate cancer (PC) associated with increased c-Myc upregulation with advancing disease.

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  • Second malignant neoplasms (SMNs) are serious complications that can develop after pediatric cancer treatment, and this study investigates the genetic factors that may influence their occurrence.
  • The researchers conducted whole-exome sequencing on 14 pediatric patients with SMNs and found that 35.7% had harmful genetic mutations in cancer-predisposing genes, particularly in TP53 and DICER1, which is significantly higher than in a control group.
  • The findings suggest that genetic variations, along with treatments like platinum drugs, contribute to the risk of developing secondary cancers, indicating the need for thorough genetic analysis to better predict and manage these risks in pediatric cancer survivors.
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  • Minimal residual disease (MRD) refers to the few cancer cells that persist in the body after treatment, which is particularly important in managing blood cancers like acute lymphoblastic leukemia (ALL).
  • This study introduces a new method for detecting MRD using droplet digital PCR (ddPCR) to identify specific genetic mutations, demonstrating a sensitivity level of 1E-4, which outperformed traditional PCR in some cases.
  • The ddPCR-MRD method showed promising results across various cancer types, as it could also detect low levels of cancer cells in stored ovarian tissue from pediatric patients, suggesting its potential as a versatile tool for MRD detection beyond just ALL.
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Background: Diffuse large B-cell lymphoma (DLBCL) is classified into two molecular subtypes according to its cell of origin: germinal center B-cell (GCB) subtype and activated B-cell/non-GCB subtype. This latter subtype shows a poorer prognosis in adults. However, in pediatric DLBCL, the prognostic impact of the subtype is yet to be clarified.

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  • - Omenn syndrome (OS) is a rare, severe form of combined immunodeficiency that requires stem cell transplantation, typically with high doses of chemotherapy to eliminate faulty T-cells, but optimal regimens are still being studied.
  • - A case study describes a successful stem cell transplant in a one-month-old boy with OS using a reduced dose of busulfan, along with fludarabine and anti-thymocyte globulin, leading to good engraftment without signs of graft-versus-host disease.
  • - Effective management of autoreactive symptoms with immunosuppressants prior to transplantation is crucial, and using reduced intensity conditioning (RIC) may offer a promising approach for achieving stable engraftment in OS patients. *
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Atopic dermatitis (AD) is a chronic and relapsing multifactorial inflammatory skin disease that also affects dogs. The oral and gut microbiota are associated with many disorders, including allergy. Few studies have addressed the oral and gut microbiota in dogs, although the skin microbiota has been studied relatively well in these animals.

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  • 6-Mercaptopurine (6-MP) is used to treat pediatric leukemia and lymphoma, but genetic variations in the NUDT15 gene can lead to severe side effects like myelosuppression.* -
  • Patients with certain NUDT15 variants have higher levels of a toxic compound in their blood, which is linked to increased risk of myelosuppression during treatment with 6-MP.* -
  • A study found that lower NUDT15 protein levels are strongly associated with adverse effects of 6-MP, highlighting the importance of genetic testing for tailored treatment strategies.*
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  • Liquid biopsy is a noninvasive method using blood samples to detect genomic changes, offering an alternative to traditional tissue biopsies for patients with neuroblastoma (NB).
  • In this study, researchers analyzed cell-free DNA (cfDNA) from 24 NB patients at diagnosis, focusing on MYCN amplification and 11q loss of heterozygosity (11qLOH) using droplet digital PCR (ddPCR).
  • The analysis showed a strong correlation (0.88) between MYCN copy numbers in cfDNA and tumor DNA, indicating that cfDNA is a reliable source for assessing these genomic factors in NB patients.
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The proto-oncogene cellular myelocytomatosis (c-Myc) is a transcription factor that is upregulated in several human cancers. Therapeutic targeting of c-Myc remains a challenge because of a disordered protein tertiary structure. The basic helical structure and zipper protein of c-Myc forms an obligate heterodimer with its partner MYC-associated factor X (MAX) to function as a transcription factor.

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There is no established treatment for patients with acute promyelocytic leukemia (APL) refractory to targeted therapies with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO). We report here a case of an 8-month-old girl with APL who failed standard ATRA-combined chemotherapy. Although molecular remission was achieved after introducing ATRA/ATO combination therapy, molecular relapse occurred during the ATO consolidation courses.

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Histiocytic neoplasms, such as Langerhans cell histiocytosis (LCH) and disseminated juvenile xanthogranuloma (JXG), can involve the liver and sometimes cause liver failure. We aimed to classify non-LCH histiocytic proliferating disorders that do not exhibit typical disseminated JXG histology. We examined four pediatric patients who presented with liver failure and splenomegaly.

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Vedolizumab, an immunosuppressive drug that acts locally on the gastrointestinal tract, is mainly used for the treatment of inflammatory bowel disease, and has been reported to be effective against gastrointestinal acute graft-versus-host disease (GI-aGVHD) in adults. However, there is insufficient evidence for pediatric GI-aGVHD. We used vedolizumab to treat three cases of GI-aGVHD in patients aged 1.

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  • The study investigates genetic variation's impact on second malignant neoplasms (SMNs) in children previously treated for leukemia or lymphoma, focusing on NUDT15 gene variants.
  • A higher prevalence of NUDT15 hypomorphic variants was found in children with SMNs compared to the general population, suggesting a potential link.
  • Treatment with the chemotherapy drug 6-mercaptopurine (6-MP) resulted in increased DNA damage in cells lacking functional NUDT15, indicating these variants may heighten SMN risk in affected patients.
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  • Lymphoblastic lymphoma (LBL) and acute lymphoblastic leukemia (ALL) are related but differ in their molecular genetics, particularly in B-cell cases, which are less understood due to their rarity.
  • Researchers conducted whole exome sequencing (WES) on seven patients with TCF3-PBX1-positive B-cell LBL to identify genetic alterations.
  • Findings revealed recurrent mutations in the KMT2D gene and 6q loss of heterozygosity, indicating potential relationships with the disease's severity and outcomes, highlighting the need for further comparative studies with B-ALL.
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Cellular senescence is a state of permanent proliferative arrest induced by a variety of stresses, such as DNA damage. The transcriptional activity of p53 has been known to be essential for senescence induction. It remains unknown, however, whether among the downstream genes of p53, there is a gene that has antisenescence function.

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  • Atypical Burkitt leukemia/lymphoma (preBLL) has distinct molecular features that set it apart from classical Burkitt lymphoma (BL), particularly in their genetic mutations and translocation patterns.
  • A case study of an infant with preBLL revealed a mix of characteristics from both preBLL and classical BL, differing in immunophenotyping and genetic mutations.
  • The findings suggest that not all preBLL cases are easily distinguishable, highlighting the need for more research to better understand the variations within preBLL.
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Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) blockade is a promising therapy for hematological malignancies. However, the association of PD-L1 expression with the clinicopathological features and prognosis in pediatric ALK-positive anaplastic large cell lymphoma (ALCL) remains unclear. Using PD-L1/ALK immunofluorescence double staining, we evaluated the PD-L1 expression on tumor cells/tumor-infiltrating immune cells (TIICs) and the quantity of TIICs in 54 children with ALK-positive ALCL treated with the ALCL99 protocol.

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Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many high-risk pediatric hematological malignant diseases (MD) and several nonmalignant diseases (NMD), including primary immune deficiencies. Infections must be managed to obtain better outcomes after HSCT. In this prospective observational study, viral monitoring was performed on 74 pediatric patients with MD and NMD who underwent HSCT.

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Chronic graft-versus-host disease (cGVHD) is a serious complication after allogeneic stem cell transplantation. There are no well-established treatment options for cGVHD after primary steroid-based treatment. Ibrutinib showed clinical benefit with an acceptable safety profile in steroid-dependent/refractory cGVHD patients in a Phase 1b/2 study (PCYC-1129-CA, NCT02195869), with which it was approved in the United States for adult cGVHD patients after failure of ≥1 systemic treatments.

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