Publications by authors named "Yasukazu Kawai"
Rationale: Crystalline light chain inclusion-associated kidney disease affects mainly tubular epithelial cells and is often clinically manifested as Fanconi syndrome. However, only very few case reports about the crystalline deposits within the podocytes are available, and the nature of the pathogenic monoclonal light chain implicated in these cases is still unknown. We report a case of crystalline inclusion-associated kidney disease manifested as crystalline podocytopathy in which we identified the complete structure of the pathogenic monoclonal light chain as belonging to the germ-line gene of Vκ1-39.
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- Controlling serum uric acid (sUA) levels is crucial during chemotherapy as high levels increase the risk of tumor lysis syndrome (TLS) and kidney issues in cancer patients.
- A study in Japan compared the effectiveness and safety of febuxostat and allopurinol for preventing high sUA in patients with malignant tumors undergoing chemotherapy.
- Results showed febuxostat was non-inferior to allopurinol in reducing sUA levels, with similar safety profiles for both medications.
Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. This subanalysis evaluated the efficacy and safety of lenvatinib in Japanese patients who participated in SELECT. Outcomes for Japanese patients (lenvatinib, n = 30; placebo, n = 10) were assessed in relationship to the SELECT population (lenvatinib, n = 261; placebo, n = 131).
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- The clinical path for treating acute myeloid leukemia (AML) at the hospital has been in place since 2003, involving laboratory technologists who explain test results to patients and their families using a view-sharing microscope.
- Between July 2003 and October 2014, 56 patients were involved, with a median age of 62 and average explanation time of 40 minutes, leading to improved understanding of their disease and its treatment as indicated by feedback surveys.
- The hospital has enhanced the explanation process by creating a better environment and improving privacy, while hematological laboratory technologists actively participate in medical conferences to collaborate with other healthcare providers to enhance patient care and satisfaction.
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- * This study tested a combination of F-araA and carboplatin on leukemia cells to see if it could enhance the effectiveness of treatments by targeting DNA repair mechanisms.
- * The findings showed that using both drugs together increased their effectiveness, suggesting this combo could be a promising new therapy for relapsed or drug-resistant lymphoma cases.
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- - This study explored the best high dose of cytosine arabinoside (ara-C) when combined with fludarabine, granulocyte colony-stimulating factor, and mitoxantrone (FLAGM) for adult patients with acute myeloid leukemia that has come back or resisted treatment.
- - Nine patients participated, receiving ara-C at increasing doses (8, 12, and 16 g/m2), leading to grade 4 blood-related side effects, while the most frequent non-blood-related side effects were mild, mainly nausea, vomiting, diarrhea, and rash.
- - The treatment FLAGM with high-dose ara-C proved to be safe, and the study recommended a dosage of 2 g
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- A multicenter trial investigated the effectiveness of intensified maintenance chemotherapy for adults with newly diagnosed acute promyelocytic leukemia, where 94% of patients achieved complete remission.
- In this study with 267 assessable patients, there was no significant difference in disease-free survival between those receiving intensified maintenance chemotherapy and those simply observed, with predicted 6-year disease-free survival rates of 63.1% and 79.8%, respectively.
- Notably, the observation group had a much higher overall survival rate of 98.8%, compared to 86.2% in the chemotherapy group, indicating that intensified maintenance chemotherapy may actually worsen survival chances for patients who test negative for the PML-RARalpha fusion transcript after consolidation therapy
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- The study focuses on the treatment of resistant acute myeloid leukemia (AML) using a combination of cytarabine (ara-C) and fludarabine, analyzing how fludarabine triphosphate enhances the activity of ara-C.
- Researchers examined two cell lines (R1 and R2) that showed significant resistance to ara-C compared to standard HL-60 cells, highlighting reduced deoxycytidine kinase activity and lower production of active metabolites.
- The findings suggest that while fludarabine can enhance the cytotoxic effects of ara-C in some cells, the effectiveness is compromised in more resistant variant cells (like R2) due to reduced accumulation of fludarabine triphosphate and altered
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- The study examines how the deoxyadenosine analogue F-ara-A exerts its cytotoxic effects by integrating into DNA after being converted to F-ara-ATP, with resistance mechanisms being explored in a resistant variant of L1210 mouse leukemia cells (L1210/F).
- L1210/F cells displayed over 41-fold resistance to F-ara-A and had 55% lower dCK activity, showing limited cross-resistance to other analogues like ara-C despite slight similarities in their triphosphate accumulation.
- High levels of dATP and dCTP in L1210/F cells inhibited F-ara-A incorporation into DNA, but treatment with hydroxyurea improved F-ara-A effectiveness by
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- * The trial revealed a 92.3% complete hematologic response, with 43.6% achieving complete cytogenetic response and 20.5% a major partial response, although dose adjustments were needed for many due to side effects.
- * Most adverse events were reversible, and despite challenges like neutropenia and thrombocytopenia, the findings suggest imatinib mesylate is a recommended treatment for patients in the chronic phase of CML.
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- Previous studies highlight that fludarabine targets DNA repair, and this study investigates how carboplatin and F-ara-A interact regarding DNA repair inhibition.
- Using human quiescent lymphocytes, the research employed the alkaline comet assay to evaluate DNA damage from carboplatin, revealing a dose-dependent increase in DNA incision that was reversible after 4 hours.
- The combination of carboplatin and F-ara-A led to enhanced apoptosis and cytotoxic effects, whereas carboplatin alone showed minimal damage, suggesting that carboplatin creates an opportunity for F-ara-A to inhibit DNA repair in dormant cells.
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- The prognosis for adults with BCR-ABL-positive acute lymphoblastic leukemia (ALL) is poor, typically requiring allogeneic hematopoietic stem cell transplantation for long-term survival.
- A new phase 2 trial by the Japan Adult Leukemia Study Group (JALSG) using intensive chemotherapy and imatinib reported that 96% of patients achieved complete remission after one treatment cycle.
- The combination therapy demonstrated a promising efficacy with high-quality remission rates and allowed 63% of patients to proceed to transplantation, although more research is needed due to the limited sample size and short follow-up.
Article Synopsis
- * A major cytogenic response is a key indicator of survival for patients on imatinib, and the drug's effectiveness can be predicted using a genome-wide microarray.
- * Resistance to imatinib arises from mutations in the BCR-ABL gene, suggesting that combining imatinib with other treatments might enhance efficacy; recent trials have compared imatinib alone with combinations of other agents.
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- Complete elimination of plasma cell dyscrasia is crucial for reducing amyloid deposits, and while high-dose melphalan can induce a hematological response, it has a limited success rate of around 40%.
- The text discusses a unique case where reduced intensity allogeneic stem cell transplantation (RIST) successfully treated a patient with primary amyloidosis and nephrotic syndrome, who previously only had partial improvement from high-dose melphalan.
- RIST shows promise as a viable treatment option that may lead to complete hematological response and recovery from nephrotic syndrome, while maintaining manageable toxicity levels.
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- A 63-year-old man with myelodysplastic syndrome (MDS) developed a large skin ulcer diagnosed initially as infectious dermatitis but worsened despite antibiotic treatment.
- A biopsy revealed severe neutrophil infiltration, leading to a diagnosis of pyoderma gangrenosum (PG), prompting treatment with corticosteroids, starting with high doses of methylprednisolone.
- The skin lesion showed significant improvement after treatment, allowing for the patient's discharge, and there was no recurrence of PG despite the progression of MDS to leukemia later on.
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- Enhanced DNA repair activity helps cells resist damage from alkylating agents like BCNU, with a focus on the differences between resistant (CEM-R) and sensitive (CEM-S) human leukemia cells.
- CEM-R cells demonstrated a 10-fold increase in resistance to BCNU compared to CEM-S cells, completing DNA repair faster and more effectively despite higher drug concentrations.
- The findings indicate that improved excision repair mechanisms in CEM-R cells could inform strategies to overcome cancer cell resistance to chemotherapy.
Survivin, a unique member of the inhibitor of the apoptosis protein (IAPs) family, is over-expressed in many cancers but not in normal differentiated adult tissues. Using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we investigated patterns of survivin gene expression in a group of 12 patients with chronic myeloid leukemia (CML) representing both chronic and blastic phases of the disease. All 6 patients in chronic phase CML were uniformly negative for the survivin transcript, in contrast to 4 Philadelphia chromosome-positive (Ph+) CML patients in blastic crisis, all of whom (100%) were positive for survivin with tangible levels of expression.
View Article and Find Full Text PDFWe have sought to clarify the potential activity of the S-phase-specific antileukemic agent 1-beta-D-arabinofuranosylcytosine (ara-C), an inhibitor of DNA synthesis, in quiescent cells that are substantially non-sensitive to nucleoside analogues. It was hypothesized that the combination of ara-C with DNA damaging agents that initiate DNA repair will expand ara-C cytotoxicity to non-cycling cells. The repair kinetics, which included incision of damaged DNA, gap-filling by DNA synthesis and rejoining by ligation, were evaluated using the single cell gel electrophoresis (Comet) assay and the thymidine incorporation assay.
View Article and Find Full Text PDFThe capacity to repair DNA damage is an important factor that affects the therapeutic outcome in cancer treatment. To clarify the cellular repair response, we investigated the kinetics of DNA excision repair initiated by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in human leukemia CCRF-CEM cells at an exponential growth phase in vitro. Using the alkaline single-cell gel electrophoresis (comet) assay, we quantitated the repair kinetics as the amount of DNA single-strand breaks that were generated from the incision and were diminished by the rejoining in the repair process.
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- Glucocorticoids are critical for treating acute lymphoblastic leukemia (ALL), but resistance, particularly in B-cell lines, has not been extensively studied compared to T-cell lines.
- A new DEX-resistant B-cell leukemia cell line (697/DEX) was created, showing over 430-fold resistance compared to its parental line, and resistance was linked to lower glucocorticoid receptors and higher levels of glutathione (GSH).
- Inhibiting GSH synthesis with L-buthionine-(S, R)-sulfoximine (BSO) reinstated DEX sensitivity, suggesting that managing GSH levels might help to combat chemotherapy resistance in B-cell lineage ALL.
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- Alkylating agents and platinum analogues start DNA repair processes that involve damage detection, removal, and re-synthesis to fix broken strands.
- The study found that fludarabine nucleoside (F-ara-A) can be incorporated during this repair process, which disrupts effective DNA repair.
- Results showed that while normal lymphocytes can efficiently repair DNA damage from UV exposure, the presence of F-ara-A significantly hinders this repair, suggesting its potential as a new treatment for cancer, especially in resistant cells.