Publications by authors named "Hirohito Kubota"

Article Synopsis
  • Temcell is a mesenchymal stem cell therapy approved in Japan for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD), but its effectiveness in children has not been well documented.
  • In a study of twelve pediatric patients treated with Temcell, an 83% overall response rate was observed after the first therapy cycle, with significant improvements noted, such as a reduction in prednisone dosage.
  • The therapy showed a good safety profile, with a three-year overall survival rate of 69.4%, but more research is needed to optimize its use in combination with other treatments.
View Article and Find Full Text PDF
Article Synopsis
  • * The study found a distinct downregulated miRNA profile (miR-low cluster [MLC]) associated with significantly shorter event-free survival, particularly in patients with hyperdiploid ALL, indicating a crucial prognostic factor.
  • * Integration of miRNA and mRNA data highlighted key genetic features in the MLC, including MYC target enrichment and low expression of DICER1, offering a novel molecular stratification that could improve clinical management of BCP-ALL. *
View Article and Find Full Text PDF

Thyroid involvement is rare in pediatric Langerhans cell histiocytosis (LCH). It may cause airway narrowing, leading to acute-onset respiratory distress. Severe cases may require emergent surgical interventions such as thyroidectomy, which should be avoided in children due to higher rates of complication, particularly in infancy.

View Article and Find Full Text PDF

There is no clear consensus on the most effective treatment for relapsed/refractory high-risk neuroblastoma (NB). We retrospectively assessed seven NB patients with relapsed/refractory disease who received high-dose carboplatin-irinotecan-temozolomide (HD-CIT). Five of seven patients showed favorable therapeutic response (complete remission or partial remission).

View Article and Find Full Text PDF

There are few reports of the long-term efficacy of splenectomy in children with immune thrombocytopenia (ITP). In a 33-year period, we performed splenectomies in 23 pediatric patients with ITP at a single institution in Japan. The age at surgery was 5-22 years with a median of 10 years.

View Article and Find Full Text PDF

Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development of novel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 () and RUNX1-Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies.

View Article and Find Full Text PDF

Glioblastoma is the most common adult brain tumour, representing a high degree of malignancy. Transcription factors such as RUNX1 are believed to be involved in the malignancy of glioblastoma. RUNX1 functions as an oncogene or tumour suppressor gene with diverse target genes.

View Article and Find Full Text PDF

A lack of practical resources in Japan has limited preclinical discovery and testing of therapies for pediatric relapsed and refractory acute lymphoblastic leukemia (ALL), which has poor outcomes. Here, we established 57 patient-derived xenografts (PDXs) in NOD.Cg-Prkdc ll2rg /ShiJic (NOG) mice and created a biobank by preserving PDX cells including three extramedullary relapsed ALL PDXs.

View Article and Find Full Text PDF

Malignancy of medulloblastoma depends on its molecular classification. Sonic Hedgehog (SHH)-type medulloblastoma with p53 mutation was recognized as one of the most aggressive types of tumors. We developed a novel drug, chlorambucil-conjugated PI-polyamides (Chb-M'), which was designed to compete with the RUNX consensus DNA-binding site.

View Article and Find Full Text PDF

Pediatric colorectal cancer (CRC) is extremely rare, with little information about genetic profiles compared with adult CRC. Here, a 13-year-old male with advanced CRC underwent cancer gene panel testing, which detected 4 genetic abnormalities ( MET amplification in addition to TP53 , SMAD4 , and CTNNA1 mutations) that might be associated with a poor prognosis. Based on high-level MET amplification, he received a multikinase inhibitor, cabozantinib, after failure of first-line and second-line chemotherapy, resulting in transient disease stabilization.

View Article and Find Full Text PDF
Article Synopsis
  • Lineage switch during leukemic relapse is rare, particularly noted in cases of KMT2A-rearranged infant leukemia, but the mechanisms behind it are not fully understood.
  • This report discusses a female infant who went into remission for acute monocytic leukemia but relapsed as acute lymphocytic leukemia six months later, both cases being KMT2A-MLLT3-rearranged.
  • Whole exome sequencing of bone marrow samples revealed two loss-of-function mutations in PAX5 in the relapse, suggesting these mutations were significant in driving the switch from one type of leukemia to another.
View Article and Find Full Text PDF

The emergence of tyrosine kinase inhibitors as part of a front-line treatment has greatly improved the clinical outcome of the patients with Ph acute lymphoblastic leukemia (ALL). However, a portion of them still become refractory to the therapy mainly through acquiring mutations in the BCR-ABL1 gene, necessitating a novel strategy to treat tyrosine kinase inhibitor (TKI)-resistant Ph ALL cases. In this report, we show evidence that RUNX1 transcription factor stringently controls the expression of BCR-ABL1, which can strategically be targeted by our novel RUNX inhibitor, Chb-M'.

View Article and Find Full Text PDF
Article Synopsis
  • * High-dimensional single-cell mass cytometry revealed a shift in T cell types from naïve to effector forms, indicating a T helper 1-polarized immune profile and an increase in effector regulatory T cells at relapse.
  • * RNA transcriptome analysis showed that immune-related pathways in leukemia cells are upregulated during relapse, suggesting interactions with the tumor environment and highlighting potential targets for future immunotherapy strategies.
View Article and Find Full Text PDF

Patients with refractory graft-versus-host disease (GVHD) have a dismal prognosis. Therefore, novel therapeutic targets are still needed to be identified. Runt-related transcriptional factor (RUNX) family transcription factors are essential transcription factors that mediate the essential roles in effector T cells.

View Article and Find Full Text PDF

Malignant rhabdoid tumor (MRT) is a rare and highly aggressive pediatric malignancy primarily affecting infants and young children. Intensive multimodal therapies currently given to MRT patients are not sufficiently potent to control this highly malignant tumor. Therefore, additive or alternative therapy for these patients with a poor prognosis is necessary.

View Article and Find Full Text PDF

The clinical outcome of high-dose chemotherapy (HDC) with autologous stem cell transplantation was retrospectively analyzed in six patients with recurrent intracranial germinoma. Prior to HDC, all patients achieved complete remission after platinum and ifosfamide-based chemotherapy. A melphalan-based conditioning regimen was administered in either a single cycle or multiple sequential cycles.

View Article and Find Full Text PDF

We report on three cases of pediatric acute lymphoblastic leukemia presenting with bone pain and arthralgia as initial symptoms. At the first visit, their primary signs were recurrent bone pain and arthralgia, without significant peripheral blood abnormalities. It took 2-4 months to confirm the diagnosis from the onset of arthralgia due to this atypical presentation of the disease.

View Article and Find Full Text PDF