Publications by authors named "Jun-ichi Imai"

Article Synopsis
  • The study aims to identify genetic biomarkers that can help differentiate between ovarian serous carcinoma (OSC) and ovarian clear cell carcinoma (OCCC), two distinct types of epithelial ovarian cancer with different characteristics.
  • Researchers analyzed RNA from 57 surgical specimens of EOC patients using DNA microarray technology to find gene expression differences between the two cancer types.
  • They identified 10 candidate genes that were up-regulated in OCCC compared to OSC, suggesting these genes could serve as effective diagnostic markers and may provide insights into the distinct behaviors of these carcinomas, including OCCC's resistance to chemotherapy.
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Neural precursor cell-expressed developmentally downregulated 4-1 (NEDD4) is an E3 ligase that leads to the degradation of proteins, including estrogen receptor α. We evaluated whether the expression level of NEDD4 affected the outcome of breast cancer patients. We performed a retrospective cohort study enrolling 143 patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer.

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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.

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  • Epithelial ovarian cancer (EOC) is a diverse disease with various mutations, and this study aimed to analyze the genetic mutations in EOC patients to understand their impact on the disease's clinicopathological characteristics.
  • Researchers collected and analyzed genetic data from 80 EOC surgical samples, identifying mutations in 66 cases, with TP53, PIK3CA, and KRAS being the most common mutated genes.
  • The study found that certain mutations were linked to age and cancer subtype, influencing patient outcomes, with PIK3CA and KRAS mutations typically associated with better progression-free survival, while TP53 mutations correlated with poorer outcomes.
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  • * In a study of 122 NSCLC patients, β-catenin was present in 24% of tumors, but significantly less in adenocarcinomas, and its presence correlated with lower CD8 and CD11c cell infiltration.
  • * Patients with β-catenin-positive NSCLC had worse survival outcomes and a higher tumor mutation burden, despite lower levels of programmed death-ligand 1 expression.
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  • Endometrial carcinoma (EC) is a diverse disease with various histological subtypes and genetic changes; this study aimed to explore the mutational landscape of EC tumors and how these mutations relate to patient outcomes.
  • A total of 100 surgical tumor samples were analyzed, revealing mutations in 91% of the cases, primarily affecting genes like PTEN, PIK3CA, and TP53, each associated with different clinicopathological features and survival rates.
  • The findings suggest that understanding these mutations could help develop targeted treatments and improve survival rates for EC patients in the future.
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  • The study investigated genetic mutations in 55 surgical tumors from stage IB-IIB cervical cancer patients to understand their role in tumor progression and treatment outcomes.
  • A total of 52 mutations were found in 63.6% of the patients, with PIK3CA being the most common mutation, and the presence of mutations correlated with pelvic lymph node metastasis and worse overall survival.
  • The findings suggest that analyzing multiple genetic mutations can serve as a predictive biomarker for metastasis and prognosis in early-stage cervical cancer.
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Background: In patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMN), we aimed to develop a novel blood-based biomarker utilizing a gene-expression profile for the detection of pancreatic malignancies, such as IPMN-derived carcinoma (IPMC) or pancreatic ductal adenocarcinoma (PDAC).

Patients And Methods: We enrolled 40 patients with pancreatic tumors (24 BD-IPMNs, four IPMCs and 12 PDACs) and identified the characteristic gene-expression profiles in pancreatic malignancies. Subsequently, we constructed a gene-expression scoring system for the proper diagnosis of pancreatic malignancies.

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  • Cancer treatment with immune checkpoint inhibitors often lacks reliable predictive biomarkers, but the study suggests that the expressions of PD-L1 and tumor mutation burden (TMB) could be promising indicators.
  • The research evaluated 92 non-small-cell lung cancer patients through whole-exome sequencing to calculate TMB and analyzed cancer-related gene mutations along with PD-L1 expression and tumor-infiltrating lymphocytes.
  • The findings revealed that TMB was significantly higher in certain demographics (like men and smokers) and specific mutation statuses, with a suggestion that TMB could serve as an effective biomarker linked to EGFR and TP53 mutations for predicting treatment response.
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Patient-derived tumor xenograft models represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture; however, their use is low-throughput and costly. To overcome this limitation, patient-derived tumor organoids (PDOs) were established from human lung, ovarian and uterine tumor tissues, among others, to accurately and efficiently recapitulate the tissue architecture and function. PDOs were able to be cultured for >6 months, and formed cell clusters with similar morphologies to their source tumors.

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Article Synopsis
  • Tumor mutation burden (TMB) may indicate the presence of neoantigens in tumors and help predict responses to immune checkpoint inhibitors, although its impact on prognosis, particularly in non-small cell lung cancer (NSCLC), remains unclear.* -
  • In a study of 90 NSCLC patients who had surgery without prior chemotherapy or immunotherapy, higher TMB levels were linked to significantly worse overall survival and disease-free survival rates.* -
  • The findings suggest that high TMB is a negative prognostic factor in NSCLC, indicating that using immune checkpoint inhibitors after surgery could potentially improve patient outcomes.*
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  • Lung adenocarcinoma (ADC) patients without targetable gene mutations face poor prognoses, highlighting the need for new therapeutic targets.
  • The protein FAM83B is linked to the EGFR signaling pathway and is found to be highly expressed in tumors from certain demographics, particularly in males, smokers, and those with wild-type EGFR.
  • Increased FAM83B expression correlates with worse disease-free and overall survival in ADC patients, suggesting it could serve as a prognostic marker and a new therapeutic target, especially for tumors featuring wild-type EGFR.
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The T-box 19 (TBX19) gene encodes a transcription factor characterized by a highly conserved DNA-binding motif (T-box). Recent studies have revealed that TBX19 has been identified as one of the genes activated by KRAS mutations, and is upregulated in colon adenoma. These results indicate that TBX19 may work as an oncogene in colorectal cancer (CRC).

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In recent years, human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) have been widely used to develop evaluation systems for drug cardiotoxicity, including the arrhythmia caused by QT prolongation. To accurately assess the arrhythmogenic potential of drugs, associated with QT prolongation, we developed an evaluation system using hiPS-CMs and gene expression analysis. hiPS-CMs were treated with 8 arrhythmogenic and 17 non-arrhythmogenic drugs at several concentrations for 24 hr to comprehensively analyze gene expression.

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Basaloid squamous cell carcinoma of the esophagus (BSCE) is a rare variant of squamous cell carcinoma that is difficult to distinguish from other carcinomas by preoperative endoscopic biopsy because of its histological varieties. Accurate diagnosis is essential for adequate treatment, and the methods proposed so far (e.g.

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  • Dipeptidase 1 (DPEP1) is an important enzyme in metabolism, previously thought to suppress tumors but linked to poorer outcomes in colorectal cancer (CRC).
  • * The study investigated DPEP1 expression in CRC tissues using advanced techniques and found higher levels in cancerous versus non-cancerous tissue.
  • * Despite increased DPEP1 correlating with lymph node metastasis, there was no connection with other cancer markers, suggesting a need for more research on its role in CRC.
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The pathogenesis of multiple myeloma (MM) has not yet been fully elucidated. Our microarray analysis and immunohistochemistry revealed significant up-regulation of growth arrest-specific gene 6 (Gas6), a vitamin K-dependent protein with a structural homology with protein S, in bone marrow (BM) cells of MM patients. ELISA showed that the serum levels of soluble Gas6 were significantly increased in the MM patients when compared with healthy controls.

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Personalized therapy for non‑small cell lung cancer (NSCLC), particularly lung adenocarcinoma, has recently been significantly improved by the discovery of various molecular targets. However, this has not been the case for lung squamous cell carcinoma (SCC). In the present study, we identified the family with sequence similarity 83, member B (FAM83B) as a candidate marker for SCC through a comprehensive gene expression analysis and examined its correlations with various clinicopathological factors.

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Gene amplification is a major genetic alteration in human cancers. Amplicons, amplified genomic regions, are believed to contain "driver" genes responsible for tumorigenesis. However, the significance of co-amplified genes has not been extensively studied.

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract that are diagnosed by c-kit staining in most cases. A lysosomal cysteine proteinase termed cathepsin L has been commonly associated with malignancy in several cancer types, but this finding has not been reported for GISTs. We analyzed the cathepsin L mRNA and protein expression in GISTs.

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Platinum is recognized as a harmless metal and is widely used in many industrial products. Recent studies have proposed that platinum in the form of nanoparticles has antioxidant properties, suggesting potential uses for platinum nanoparticles as additives in foods and cosmetics, with direct exposure consequences for humans. However, the influence of platinum nanoparticles on humans has not been sufficiently evaluated, thus far.

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We analyzed the mRNA diversity of genes after inducing neuronal differentiation in human NT2 teratocarcinoma cells using all-trans retinoic acid (RA). DNA microarray analyses of cells treated with RA identified 358 RA-responsive genes. mRNA diversity analysis revealed that 274 genes produced multiple protein-coding transcripts by alternative splicing.

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Transcriptomics is an objective index that reflects the overall condition of cells or tissues, and transcriptome technology, such as DNA microarray analysis, is now being introduced for the quality control of medical products. In this study, we applied DNA microarray analysis to evaluate the character of Japanese encephalitis (JE) vaccines. When administered into rat peritoneum, Vero cell-derived and mouse brain-derived JE vaccines induced similar gene expression patterns in liver and brain.

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Constitutive nuclear factor (NF)-kappaB activation is thought to be involved in survival, invasion, and metastasis in various types of cancers. However, neither the subtypes of breast cancer cells with constitutive NF-kappaB activation nor the molecular mechanisms leading to its constitutive activation have been clearly defined. Here, we quantitatively analyzed basal NF-kappaB activity in 35 human breast cancer cell lines and found that most of the cell lines with high constitutive NF-kappaB activation were categorized in the estrogen receptor negative, progesterone receptor negative, ERBB2 negative basal-like subtype, which is the most malignant form of breast cancer.

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Appropriate resources and expression technology necessary for human proteomics on a whole-proteome scale are being developed. We prepared a foundation for simple and efficient production of human proteins using the versatile Gateway vector system. We generated 33,275 human Gateway entry clones for protein synthesis, developed mRNA expression protocols for them and improved the wheat germ cell-free protein synthesis system.

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