Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Ultrastructural analysis has declined in diagnostic pathology since the advent of immunohistochemistry for formalin-fixed paraffin-embedded tissues. To reevaluate the utility of ultrastructural analysis, we adopted the osmium maceration method for scanning electron microscopy (SEM) of formalin-fixed surgical specimens: renal oncocytoma, chromophobe renal cell carcinoma (ChRCC), and tumors categorized as other oncocytic tumors of the kidney (OOT). Light microscopy and immunohistochemistry have revealed that these tumors have overlapping features. SEM observation of the formalin-fixed tumors highlighted distinct morphological features: The oncocytomas contained large mitochondria with vesicular cristae; ChRCCs harbored small mitochondria with microvesicles, and OOTs showed abundant but small mitochondria with lamellar cristae. Quantitative morphometry confirmed that the number of mitochondria in oncocytomas and OOTs exceeded that of non-neoplastic lesions, whereas ChRCCs contained fewer mitochondria. In addition, mitochondria in ChRCCs and OOTs were smaller than those of non-neoplastic lesions, whereas mitochondria in oncocytomas were larger. Thus, SEM of formalin-fixed tissues, optimized by osmium maceration, can provide diagnostically valuable information beyond conventional histology and immunohistochemistry that may help to clarify the biology of challenging oncocytic and chromophobe renal tumors.

DOI： 10.2220/biomedres.47.77

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

MYC and MYCN oncogenes are frequently upregulated in human liver cancers, yet their functional differences remain unclear. We used a mouse model of intrahepatic cholangiocarcinoma (CCA), constructed by transposon-mediated somatic gene integration of AKT and YAP into hepatocytes, to investigate the effects of additional integration of Myc or Mycn. Both Myc and Mycn induced a poorly differentiated hepatocellular carcinoma (HCC) component, resulting in the formation of combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Interestingly, the ratio of HCC to CCA components differed significantly; AKT/YAP/Mycn (AYN) tumors exhibited a lower proportion of CCA components than AKT/YAP/Myc (AYM) tumors. To explore the underlying mechanisms, we analyzed the expression levels of genes involved in liver differentiation. We found that AYN tumors, at both the mRNA and protein levels, exhibited lower expression of HNF1B, a transcription factor that is highly expressed in human CCA but not in HCC. When Hnf1b was co-introduced with AYN, the percentage of the CCA area increased significantly. Furthermore, these tumors exhibited increased expression of TEAD proteins, which interact with YAP to initiate transcription. Notably, treatment with a YAP-TEAD inhibitor suppressed AKT/YAP/Mycn/Hnf1b tumor growth. These findings indicate that Myc and Mycn play distinct roles in the phenotypic determination of primary liver tumors and suggest that their differential effects on Hnf1b expression and subsequent TEAD activation may be a key regulatory mechanism.

DOI： 10.1111/cas.70233

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

Invasive fungal infections (IFIs) have increased in recent years due to population aging and a rising number of immunocompromised patients. The prognosis for IFIs remains poor, making accurate diagnosis and appropriate treatment essential. Low culture positivity rates and the difficulty in distinguishing IFIs from diseases such as tuberculosis on computed tomography imaging further complicate diagnosis and may delay. We encountered a case of invasive candidiasis leading to respiratory failure, in which differentiation from miliary tuberculosis on imaging was challenging. Autopsy revealed histopathological findings of eosinophilic exudates filling the alveolar spaces and poorly stained spherical fungi. Using scanning electron microscopy and DNA extraction from formalin-fixed, paraffin-embedded (FFPE) tissues, genetic analysis identified Debaryomyces hansenii, also known as Candida famata. FFPE tissue-based analytical techniques serve as valuable tools for understanding IFIs. If the causative pathogen can be identified during a patient's life, appropriate treatment can be selected, potentially improving the prognosis of IFIs.

DOI： 10.3314/mmj.25-00023

PubMed

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s00795-024-00402-2

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Other Link： https://link.springer.com/article/10.1007/s00795-024-00402-2/fulltext.html

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Recent studies have shown that transmembrane‐type tight junction proteins are upregulated in various cancers compared with their levels in normal tissues and are involved in cancer progression, suggesting that they are potential therapeutic targets. Here, we demonstrated the expression profile and a novel role of junctional adhesion molecule‐A (JAM‐A) in breast cancer. Immunohistochemistry of surgical specimens showed that JAM‐A was highly expressed from carcinoma in situ lesions, as in other adenocarcinomas, with higher expression in invasive carcinomas. High expression of JAM‐A contributed to malignant aspects such as lymph node metastasis and lymphatic involvement positivity. In breast cancer cells, JAM‐A expression status affects malignant potentials including proliferation and migration. Multilayered proteomics revealed that JAM‐A interacts with the amino acid transporter LAT1 in breast cancer cells. JAM‐A regulates the expression of LAT1 and interacts with it on the whole cell membrane, leading to enhanced amino acid uptake to promote tumor growth. Double high expression of JAM‐A and LAT1 predicts poor prognosis in patients with breast cancer. Of note, an antibody against an extracellular domain of JAM‐A suppressed the proliferation of breast cancer cells. Our findings indicate the possibility of JAM‐A‐targeted therapy ideally combined with LAT1‐targeted therapy as a new therapeutic strategy against breast cancer.

DOI： 10.1111/cas.16259

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Event date： 2025.11

Presentation type：Oral presentation (general)  

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Event date： 2025.10

Presentation type：Oral presentation (general)  

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Event date： 2025.2

Presentation type：Oral presentation (general)  

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Event date： 2023.9

Presentation type：Poster presentation  

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Presentation type：Oral presentation (general)  

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