Publications by authors named "Shun-ichiro Kageyama"
Radiotherapy (RT) combined with immune checkpoint inhibitor (ICI) therapy has attracted substantial attention due to its potential to improve outcomes for patients with several types of cancer. However, the optimal administration timepoints and drug combinations remain unclear because the mechanisms underlying RT-induced changes in immune checkpoint molecule expression and interaction with their ligand(s) remain unclear. Herein, we demonstrated the dynamics of lymphocyte-mediated molecular interactions in tissue samples from esophageal cancer patients throughout RT schedules.
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- The study aimed to assess the feasibility of using RT-PCR and direct sequencing to measure HPV DNA levels in the saliva of patients with HPV-related oropharyngeal cancer, which is important for predicting treatment outcomes.
- Nine patients undergoing treatment were monitored by collecting saliva samples at various stages of their radiotherapy, and HPV DNA levels were analyzed.
- Results showed a decrease in HPV DNA levels during and after treatment for most patients, with some experiencing disease progression, and sequencing revealed significant gene mutations in their baseline samples.
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- The SCRUM-Japan MONSTAR-SCREEN consortium is conducting a nationwide project that uses AI and multi-omics analyses for molecular profiling in patients with advanced cancers, aiming to create new treatments and diagnostics.
- The project includes the CIRCULATE-Japan study, focusing on precision medicine for resectable solid tumors and requires substantial data storage in a high-tech supercomputing system called VAPOR CONE.
- As of December 2023, over 24,000 patients have been registered, with 5.0% of those in advanced solid tumors participating in matched clinical trials, showing a 29.2% response rate and significantly improved survival rates compared to those not receiving matched therapies.
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- The study examined the effects of postoperative radiotherapy (PORT) after salvage neck dissection for patients with cervical lymph node recurrence in oral cavity cancer, focusing on outcomes like survival and recurrence rates.
- After following 51 patients for about 7.4 years, the results showed a 7-year overall survival rate of 66.3% and a recurrence-free survival rate of 54.6%, with better outcomes for younger patients and those with isolated lymph node recurrence.
- While PORT was effective, some patients experienced side effects like severe acute mucositis (35%) and less common long-term issues like osteoradionecrosis (4%) and laryngeal stenosis (2%).
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- Combining radiotherapy and immunotherapy shows potential, but the immune response after radiotherapy is still not well understood.
- Recent analyses revealed that immune cells infiltrate tumors and undergo significant changes in gene expression in response to radiotherapy over time.
- Myeloid cells, in particular, were found to have increased expression of both stimulating and suppressive immune genes, indicating they might be valuable targets for future immunotherapy approaches alongside PD-L1 inhibitors.
Serine/threonine kinase, cell division cycle 7 (CDC7) is critical for initiating DNA replication. TAK-931 is a specific CDC7 inhibitor, which is a next-generation replication stress (RS) inducer. This study preclinically investigates TAK-931 antitumor efficacy and immunity regulation.
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- - The study evaluated the effectiveness of using anterior oblique portals (AOP) in radiotherapy for early-stage glottic cancer, aiming to minimize radiation exposure to critical areas like the internal carotid arteries and pharyngeal constrictor muscle.
- - Out of 66 patients treated with radiotherapy, nearly half received AOP, and results showed no significant difference in local failure or survival rates between AOP and standard treatments, but AOP significantly reduced the incidence of severe acute mucositis.
- - The findings suggest that AOP maintains effective radiation dose coverage to the cancer while reducing harmful exposure to important surrounding structures.
Radiotherapy (RT) plus immunotherapy is a promising modality; however, the therapeutic effects are insufficient, and the molecular mechanism requires clarification to further develop combination therapies. Here, we found that the RNA virus sensor pathway dominantly regulates the cellular immune response in NSCLC and ESCC cell lines. Notably, transposable elements (TEs), especially long terminal repeats (LTRs), functioned as key ligands for the RNA virus sensor RIG-I, and the mTOR-LTR-RIG-I axis induced the cellular immune response and dendritic cell and macrophage infiltration after irradiation.
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- A retrospective study was conducted on 80 patients receiving whole-brain radiotherapy (WBRT) for leptomeningeal metastasis (LM) from lung adenocarcinoma, focusing on survival outcomes and prognostic factors.
- The median overall survival (OS) was 6.2 months, with EGFR/ALK mutant patients having significantly better OS (10.4 months) compared to wild-type patients (3.8 months).
- Key factors associated with better OS included having EGFR/ALK mutations and a good performance status (ECOG PS of 0-1), indicating that these traits may improve survival chances for patients undergoing WBRT.
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- * A study analyzed the gut microbiota of CRC patients with and without a stoma, finding reduced levels of beneficial anaerobes and methane-producing archaea in those with a stoma.
- * The presence of a stoma not only decreased microbial diversity but also affected gene functions related to beneficial molecules like short-chain fatty acids, suggesting it could complicate microbiota analyses in CRC research.
Background: Combination therapy based on radiotherapy and immune checkpoint inhibitors (ICIs) was recently reported as effective for various cancers. The radiation-induced immune response (RIIR) is an essential feature in ICI-combined radiotherapy; however, the effects of drugs used concomitantly with RIIR remain unclear. We screened for drugs that can modify RIIR to understand the mutual relationship between radiotherapy and combined drugs in ICI-combined radiotherapy.
View Article and Find Full Text PDFRadiotherapy (RT) combined with immune checkpoint inhibitors has recently produced outstanding results and is expected to be adaptable for various cancers. However, the precise molecular mechanism by which immune reactions are induced by fractionated RT is still controversial. We aimed to investigate the mechanism of the immune response regarding multifractionated, long-term radiation, which is most often combined with immunotherapy.
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- * The study compared immune responses in an oesophageal cancer cell line (KYSE450) after exposure to X-ray, proton, and carbon-ion irradiation, noting differences in gene expression shortly after treatment.
- * Findings indicated that despite initial differences, a similar immune response emerged after three days, driven by the STING-STAT1 signaling pathway, suggesting a shared mechanism for the immune reactions induced by all three types of irradiation.
Esophageal squamous cell carcinoma (ESCC) often recurs after chemoradiotherapy, and the prognosis of ESCC after chemoradiotherapy has not improved over the past few decades. The mutation process in chemoradiotherapy-resistant clones and the functional relevance of genetic alterations remain unclear. To address these problems, we performed whole-exome sequencing of 52 tumor samples from 33 patients with ESCC who received radiotherapy combined with 5-fluorouracil/platinum.
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- A retrospective study evaluated the effectiveness and safety of palliative radiation therapy (RT) for urothelial cancer patients experiencing macroscopic hematuria (MH) from 2008 to 2018, involving 25 patients.
- Results showed that 88% of patients achieved complete resolution of MH within a median of 9 days, but 41% experienced recurrences with a median relapse time of 129 days.
- The three-month hematuria-free survival rate was 52.1%, with significant differences based on prior blood transfusions, and the therapy demonstrated limited toxicities, like mild urinary pain and diarrhea.
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- The study investigates the risk of radiation pneumonitis (RP) in cancer patients with interstitial lung disease (ILD) receiving palliative radiotherapy (RT), focusing on its incidence, severity, and predictive factors.
- A retrospective review of 62 patients' medical records showed that RP occurred in various grades, with a significant number experiencing severe RP (≥Grade 3) usually within 39 days post-treatment.
- The results highlight that the pattern of ILD observed in pre-treatment CT scans is a crucial factor in predicting severe RP, suggesting that RT for these patients should be approached with caution.
Cell division cycle 7 (CDC7), a serine/threonine kinase, plays important roles in DNA replication. We developed a highly specific CDC7 inhibitor, TAK-931, as a clinical cancer therapeutic agent. This study aimed to identify the potential combination partners of TAK-931 for guiding its clinical development strategies.
View Article and Find Full Text PDFBackground/aim: To investigate the usefulness of cell-free DNA (cfDNA) in patients with oligometastasis.
Patients And Methods: This study included oligometastatic colorectal cancer (CRC) patients who underwent ablative irradiation using stereotactic body radiotherapy or proton beam therapy for metastatic lesions at a single institution. cfDNA was purified from the plasma of pretreated patients and gene mutations were analyzed by next-generation sequencing.
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- Ionising radiation is known to cause mutations in tumor cells and is an effective cancer treatment, but the mutation patterns caused by radiation are not well understood.
- Researchers created an experimental setup using oesophageal cancer cell lines to investigate mutations after radiation exposure.
- The study found specific mutation hotspots linked to repair errors from radiation damage, providing insights into the mechanisms of radiation's impact on cancer genomes.
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- The study involved 135 patients with T1-3N0M0 non-squamous non-small cell lung cancer (NSCLC), including 27 with EGFR mutations and 29 without.
- In the findings, the EGFR-mutant group had a significantly lower rate of infield failure (9%) compared to the EGFR-wild group (27%), indicating better local control.
- However, the EGFR-mutant group experienced a higher rate of out-of-field failure (67%) compared to the EGFR-wild group (40%), pointing to potential challenges in cancer control beyond the targeted treatment area.
Background: The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy (CRT) using 5-FU plus cisplatin. However, complete response (CR) rates are low at 11-25%, resulting in 9-10 months of median overall survival (OS). An improved therapeutic efficacy by combining immunotherapy with radiation has been reported in patients with locally advanced non-small cell lung cancer.
View Article and Find Full Text PDFBackground: The purpose of this study was to evaluate accelerated fractionated radiotherapy (AFRT) without elective nodal irradiation (ENI) for T3N0 glottic cancer (GC) without vocal cord fixation, especially in comparison with chemoradiotherapy (CRT) and hyperfractionated radiotherapy (HFRT) both of which included ENI.
Methods: The medical charts of patients with T3N0GC without cord fixation received definitive radiotherapy between June 2005 and March 2018 were reviewed.
Results: A total of 74 patients were analyzed.
Proton beam therapy (PBT) combined with chemotherapy, such as cis-diamminedichloroplatinum (II) (CDDP) and 5-fluorouracil (5-FU), has been employed as an alternative approach to improve clinical outcomes. PBT has been reported to be effective against esophageal cancer. However, apart from 5-FU and CDDP, almost no other drug has been tested in combined chemotherapy with PBT.
View Article and Find Full Text PDFBackground: The number of hemodialysis (HD) patients is increasing worldwide, and they are at a higher risk of cancer than the general population. Because HD patients are more likely to have inflammation, radiotherapy (RT)-induced adverse effects (AEs) are theoretically expected to be worse for HD patients. Since only a few reports have been published on this subject, we aimed to evaluate the tolerability of RT in HD patients.
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