Publications by authors named "Yasushi Kojima"

Article Synopsis
  • - The study investigates the effectiveness of S-1, a drug used after surgery for biliary tract cancer, and its relationship with certain genes involved in the metabolism of the chemotherapy drug 5-fluorouracil (5-FU).
  • - Researchers analyzed tumor samples from 183 patients and categorized them based on their DPD and TP gene levels to see how these affected recurrence-free survival (RFS) when treated with S-1.
  • - Findings indicated that patients with low levels of DPD and TP genes had better RFS benefits from adjuvant S-1, highlighting the potential prognostic significance of these genes in treatment outcomes.
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Background: Early tumor shrinkage (ETS) is a prognostic predictor for patients treated with chemotherapy in colorectal cancer, although scarce studies evaluated its potential in locally advanced pancreatic cancer (LAPC). In this exploratory analysis of JCOG1407, a randomized phase II study comparing modified 5-fluorouracil, levofolinate, irinotecan, and oxaliplatin (mFOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP), we evaluated whether ETS can predict prognosis of patients with LAPC.

Methods: Of the 126 patients enrolled in JCOG1407, 112 with measurable lesions were included in this study.

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Introduction: Hepatic arterial infusion chemotherapy (HAIC) with cisplatin and lenvatinib exhibits strong antitumor effects against advanced hepatocellular carcinoma (HCC). Higher antitumor activity is expected for the combination treatment. The aim of this trial was to evaluate the efficacy and safety of lenvatinib in combination with HAIC using cisplatin in patients with advanced HCC.

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Backgrounds: Few data are available for surveillance decisions focusing on factors related to mortality, as the primary outcome, in intraductal papillary mucinous neoplasm (IPMN) patients.

Aims: We aimed to identify imaging features and patient backgrounds associated with mortality risks by comparing pancreatic cancer (PC) and comorbidities.

Methods: We retrospectively conducted a multicenter long-term follow-up of 1864 IPMN patients.

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Desmoid tumors (DTs), also called desmoid-type fibromatoses, are locally aggressive tumors of mesenchymal origin. In the present study, we developed a novel mouse model of DTs by inducing a local mutation in the Ctnnb1 gene, encoding β-catenin in PDGFRA-positive stromal cells, by subcutaneous injection of 4-hydroxy-tamoxifen. Tumors in this model resembled histologically clinical samples from DT patients and showed strong phosphorylation of nuclear SMAD2.

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Cancer cachexia is a complex metabolic disorder accounting for ~20% of cancer-related deaths, yet its metabolic landscape remains unexplored. Here, we report a decrease in B vitamin-related liver enzymes as a hallmark of systemic metabolic changes occurring in cancer cachexia. Metabolomics of multiple mouse models highlights cachexia-associated reductions of niacin, vitamin B6, and a glycine-related subset of one-carbon (C1) metabolites in the liver.

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Background: There are no previous reports on the main causes of death in biliary tract cancer (BTC) patients. This study aimed to evaluate the main causes of death and survival rates in patients with BTC.

Methods: We retrospectively evaluated 143 patients who were diagnosed with unresectable BTC between August 2010 and March 2020.

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Oncometabolites, such as D/L-2-hydroxyglutarate (2HG), have directly been implicated in carcinogenesis; however, the underlying molecular mechanisms remain poorly understood. Here, we showed that the levels of the L-enantiomer of 2HG (L2HG) were specifically increased in colorectal cancer (CRC) tissues and cell lines compared with the D-enantiomer of 2HG (D2HG). In addition, L2HG increased the expression of ATF4 and its target genes by activating the mTOR pathway, which subsequently provided amino acids and improved the survival of CRC cells under serum deprivation.

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Comprehensive cancer genome profiling (CGP) has been nationally reimbursed in Japan since June 2019. Less than 10% of the patients have been reported to undergo recommended treatment. Todai OncoPanel (TOP) is a dual DNA-RNA panel as well as a paired tumor-normal matched test.

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Background & Aims: We investigate interrelationships between gut microbes, metabolites, and cytokines that characterize COVID-19 and its complications, and we validate the results with follow-up, the Japanese 4D (Disease, Drug, Diet, Daily Life) microbiome cohort, and non-Japanese data sets.

Methods: We performed shotgun metagenomic sequencing and metabolomics on stools and cytokine measurements on plasma from 112 hospitalized patients with SARS-CoV-2 infection and 112 non-COVID-19 control individuals matched by important confounders.

Results: Multiple correlations were found between COVID-19-related microbes (eg, oral microbes and short-chain fatty acid producers) and gut metabolites (eg, branched-chain and aromatic amino acids, short-chain fatty acids, carbohydrates, neurotransmitters, and vitamin B6).

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Article Synopsis
  • Pancreatic adenosquamous carcinoma (PASC) is a rare type of pancreatic cancer, and the study investigates the effectiveness of chemotherapy, particularly combination therapies, for treating patients with metastatic or recurrent PASC.
  • The analysis included data from 116 patients who received first-line chemotherapy at multiple institutions in Japan over a 16-year period, comparing outcomes between those on combination therapies and monotherapies.
  • Results indicated that combination therapies (like gemcitabine + nab-paclitaxel or fluorouracil/leucovorin + irinotecan + oxaliplatin) tended to provide better overall survival compared to monotherapy, suggesting they may be more beneficial for PASC patients.
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Article Synopsis
  • Indigenous bacteriophage communities, or viromes, significantly influence gut bacterial communities (bacteriomes), but their variation across populations is not yet well-researched.
  • In a study of the gut dsDNA virome in 4198 Japanese individuals, researchers identified thousands of high-quality phage genomes, including previously uncharacterized clades with different bacterial hosts.
  • The study found that factors like age, sex, lifestyle, and diet strongly affect virome structure, with disease and medication having the most significant impact, aiding our understanding of the symbiotic relationship between gut bacteria and their viruses for future medical and industrial applications.
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This study identifies signaling pathways essential for maintaining the stemness and metastatic potential of colorectal cancer cells and proposes CREB as a therapeutic target in metastatic colorectal cancer.

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Article Synopsis
  • A study investigated the effectiveness and safety of Gemcitabine plus nab-paclitaxel (GnP) compared to other treatments in older adults with unresectable pancreatic cancer (uPC).
  • The study included 233 patients aged 76 and older, focusing on overall survival and progression-free survival while utilizing propensity score-matched analyses for fair comparisons.
  • Results showed that GnP offered longer median overall survival (12.2 months) and progression-free survival (9.2 months) compared to Gemcitabine alone, although GnP had a higher but not significantly different rate of severe adverse events.
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Capecitabine plus oxaliplatin, CAPOX, therapy is one of the standardized options for adjuvant chemotherapy for colorectal cancer, but the efficacy and the safety of CAPOX in elderly patients are unclear. In this study, we investigated the relative dose intensity (RDI) and reasons for dose reduction in patients over the age of 70 (elderly group) ( = 12) and those under the age of 70 (non-elderly group) ( = 24) receiving adjuvant CAPOX therapy for colorectal cancer. The median RDIs were 71.

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Background & Aims: Medication is a major determinant of human gut microbiome structure, and its overuse increases the risks of morbidity and mortality. However, effects of certain commonly prescribed drugs and multiple medications on the gut microbiome are still underinvestigated.

Methods: We performed shotgun metagenomic analysis of fecal samples from 4198 individuals in the Japanese 4D (Disease, Drug, Diet, Daily life) microbiome project.

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Background & Aims: To identify gut and oral metagenomic signatures that accurately predict pancreatic ductal carcinoma (PDAC) and to validate these signatures in independent cohorts.

Methods: We conducted a multinational study and performed shotgun metagenomic analysis of fecal and salivary samples collected from patients with treatment-naïve PDAC and non-PDAC controls in Japan, Spain, and Germany. Taxonomic and functional profiles of the microbiomes were characterized, and metagenomic classifiers to predict PDAC were constructed and validated in external datasets.

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In the FUGA-BT trial (JCOG1113), gemcitabine plus S-1 (GS) showed non-inferiority to gemcitabine plus cisplatin (GC) in overall survival (OS) with good tolerance for patients with advanced biliary tract cancer (BTC). We performed a subgroup analysis focused on the elderly cohort of this trial. All 354 enrolled patients in JCOG1113 were classify into two groups; < 75 (non-elderly) and ≥ 75 years (elderly) group.

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Definitive chemoradiation (dCRT) is the mainstay treatment for cStage IVa esophageal squamous cell carcinoma (ESCC) with good performance status (PS), according to standard practice guidelines. Salvage surgery may incur operation complications and risk of mortality. According to the esophageal cancer practice guidelines outlined by the Japan Esophageal Society, when a tumor is residual and recurrent, chemotherapy and palliative symptomatic treatment is continued.

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JCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr).

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The prognosis of glioblastoma remains poor despite intensive research efforts. Glioblastoma stem cells (GSCs) contribute to tumorigenesis, invasive capacity, and therapy resistance. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), a stem cell marker, is involved in the maintenance of GSCs, although the properties of Lgr5-positive GSCs remain unclear.

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Background: UGT1A1 *28 and *6 polymorphism is associated with reduced enzyme activity and severe toxicities of irinotecan, especially in patients with homozygous or heterozygous for UGT1A1*28 or *6 polymorphism for both UGT1A1*28 and *6 (double-variant-type of UGT1A1 polymorphism, UGT1A1-DV). FOLFIRINOX is one of the standard treatments for metastatic pancreatic cancer (PC). The optimal dose of irinotecan as a component of the FOLFIRINOX has not been established yet for patients with UGT1A1-DV.

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Objectives: The aim of this multicenter retrospective study was to identify the optimal chemotherapeutic regimen for advanced pancreatic acinar cell carcinoma (PACC).

Methods: Fifty-eight patients with histopathologically confirmed advanced PACC who had received chemotherapy between 1996 and 2013 were enrolled. The clinical characteristics of the patients and the treatment efficacy data were collected from the medical records at 16 Japanese institutions, using standardized data collection instrument.

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