{"title":"Vitamin D derivatives inhibit mesenchymal transition of mesothelial cells and mitigate peritoneal dissemination of ovarian cancer.","authors":"Kazuhisa Fujita, Maia Hayashi, Masato Yoshihara, Satoshi Nomura, Kazuhisa Kitami, Emiri Miyamoto, Shohei Iyoshi, Kazumasa Mogi, Hiroki Fujimoto, Kaname Uno, Atsushi Kunishima, Yoshihiko Yamakita, Hiroyuki Tomita, Rino Tsutsumi, Ryota Sakamoto, Kazuo Nagasawa, Yusuke Masuo, Takumi Nishiuchi, Kiyosumi Shibata, Atsushi Enomoto, Hiroaki Kajiyama","doi":"10.1007/s00795-025-00424-4","DOIUrl":"10.1007/s00795-025-00424-4","url":null,"abstract":"<p><p>Ovarian cancer (OvCa) is a leading cause of gynecological cancer-related mortality, primarily due to peritoneal dissemination, which facilitates metastasis in the abdominal cavity. This study explored the potential of vitamin D and its synthetic derivatives in mitigating peritoneal dissemination by modulating the behavior of mesothelial cells (MCs). Vitamin D, through its receptor (VDR), is known to influence cancer progression, and our findings demonstrate that vitamin D derivatives can inhibit mesenchymal transition of MCs induced by TGF-β1, a key driver of peritoneal dissemination. This study used patient-derived primary MCs and in vivo mouse model to assess the effects of vitamin D derivatives on cell morphology, gene expression, and OvCa cell adhesion. Two vitamin D derivatives, VDR agonist, showed significant efficacy in maintaining epithelial-like MC morphology, reducing TGF-β1-induced changes, and inhibiting OvCa cell adhesion to the peritoneum, similar to calcitriol. Conversely, the VDR antagonist derivative induced MC apoptosis, highlighting the essential role of vitamin D in MC survival. These findings suggest that vitamin D derivatives could serve as promising therapeutic agents for OvCa by preserving peritoneal homeostasis and preventing metastasis. Further research is required to explore a broader range of derivatives and their underlying molecular mechanisms.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"171-182"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Three-dimensional architecture of the palmar plate of the thumb metacarpophalangeal joint in infant macaque.","authors":"Hiroko Sato, Tatsuo Shimada, Tsuguaki Hosoyama, Yutaro Shibuta, Nobuhiro Kaku","doi":"10.1007/s00795-025-00423-5","DOIUrl":"10.1007/s00795-025-00423-5","url":null,"abstract":"<p><p>The palmar plate is a crucial structural part of hand, associated with metacarpophalangeal and interphalangeal joints. Pediatric disorders involving the palmar plate of thumb metacarpophalangeal joint include trigger thumb, hyperextension, instability, and dislocation. While anatomical differences exist between children and adults, detailed microstructure evaluations in infants remain unexplored. In this study, we provide a histological and structural assessment of the previously unresolved microstructure of the palmar plate in the thumb metacarpophalangeal joint of infant Japanese macaques (Cercopithecidae, Macaca fuscata), a relevant model for human development. Histological staining (light microscopy) and scanning electron microscopy were employed to visualize the three-dimensional microstructure. The palmar plate of the infant macaque was found to contain (1) elastic fibers, (2) hyaline cartilage composed of type II collagen, and (3) type I collagen fibers arranged in distinct patterns. The cartilaginous region exhibited a reticulate fiber arrangement on its periphery, while the membranous region displayed dense and complex fibers on the proximal phalanx side and parallel on the metacarpal side, respectively. This is the first comprehensive three-dimensional investigation of the infant's thumb's palmar microanatomy, providing a foundation for understanding its development and implications for pediatric disorders.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"163-170"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Subcellular localization of pro-gastrin releasing peptide in human Ewing sarcoma cell lines.","authors":"Koji Muramatsu, Kouji Maruyama, Yosuke Honda, Hirohisa Katagiri, Yu Takahashi, Naoki Takahashi, Katsumi Aoyagi, Kenichi Mori, Mitsuru Takahashi, Toru Kameya, Takashi Sugino, Ken Yamaguchi","doi":"10.1007/s00795-025-00426-2","DOIUrl":"10.1007/s00795-025-00426-2","url":null,"abstract":"<p><p>Progastrin-releasing peptide (ProGRP), a neuropeptide, is a stable tumor marker for small cell lung carcinoma (SCLC) and other neuroendocrine tumors, such as medullary thyroid carcinoma. It has recently been reported as highly expressed in Ewing sarcoma (ES) and as a useful marker for this type of tumor. However, the mechanisms underlying ProGRP production remain unclear. This study aimed to elucidate its subcellular localization in human ES cell lines. Three ES cell lines (A-673, SK-N-MC, and SK-NEP-1) and one SCLC line (DMS 53) were transplanted into athymic mice. After 3-4 weeks, the tumors were excised, and the expression and localization of ProGRP were examined using immunohistochemistry and immunoelectron microscopy. Immunohistochemistry revealed that all three ES cell lines expressed ProGRP in a dot-like pattern in their cytoplasm, whereas SCLC cells showed a diffuse granular pattern. Immunoelectron microscopy revealed that ProGRP localized in neurosecretory granules (NSGs) in SCLC cells and in autolysosome-like structures in ES cells, with no NSGs observed in the ES cell lines. ES cells secrete high levels of ProGRP, similar to SCLC cells. However, in ES cells, ProGRP is localized in autolysosome-like structures, unlike the NSGs in SCLC, suggesting that ProGRP in ES can be transported and secreted without following the typical pathway for neuropeptides.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"193-199"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A type of pancreatic cancer cells form cell clusters from a solitary condition in a primary ciliogenesis-dependent manner.","authors":"Kenji Shirakawa, Ryota Nakazato, Tetsuhiro Hara, Kenichiro Uemura, Faryal Ijaz, Shinya Takahashi, Koji Ikegami","doi":"10.1007/s00795-025-00428-0","DOIUrl":"10.1007/s00795-025-00428-0","url":null,"abstract":"<p><p>Primary cilia are hair-like projections that protrude on most of mammalian cells and mediate reception of extracellular signals. Numerous studies have demonstrated that a variety of cancer cells including pancreatic ductal adenocarcinoma (PDAC) fail to form primary cilia. The loss of primary cilia is thought to cause carcinogenesis and progressive cell proliferation. However, the relationship of the primary cilia loss with carcinogenesis and/or cancer malignancy remains arguable. We herein examined whether ciliogenesis was increased in a model of more progressive PDAC and investigated effects of ciliogenesis on growth of PDAC using a pancreatic cancer cell line, PANC-1. The majority of PANC-1 cells in a cell cluster grown from a solitary cell possessed primary cilia. The rate of ciliogenesis was higher in cells grown from low density than in cells grown from high density. Almost all clones passing limiting dilution culture had abilities to grow primary cilia. Compared to the parental PANC-1 cells, clones that proliferated from a solitary cell showed increase in the ciliogenesis rate. Blocking ciliogenesis suppressed cell cluster formation. Our results suggest that pancreatic cancer cells that are more resistant to a solitary condition have abilities of ciliogenesis and form tumor-like cell clusters in a primary cilia-dependent manner.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"213-226"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oncocytic sinonasal papilloma in the nasal and paranasal sinuses: a case report and review of the literature.","authors":"Michiko Nishimura, Miyako Hoshino, Yuji Miyazaki, Shinnichi Sakamoto, Fumio Ide, Tsutomu Nomura, Kaoru Kusama, Kentaro Kikuchi","doi":"10.1007/s00795-025-00420-8","DOIUrl":"10.1007/s00795-025-00420-8","url":null,"abstract":"<p><p>Oncocytic sinonasal papilloma (OSP) is an uncommon, benign neoplasm characterized by papillary growths arising from the Schneiderian mucosa of the nasal and paranasal sinuses. OSP accounts for about 3-6% of all sinonasal papillomas (SPs), and clinically is often confused with inverted sinonasal papilloma (incidence 73%). Although SP shares some of the clinical characteristics of OSP, the pathogenesis differs and it is very important to distinguish between them. Here we present a case of OSP in the nasal and paranasal sinuses of a 67-year-old Japanese male, who complained of persistent left-sided nasal obstruction. A benign nasal paranasal tumor was diagnosed, and endoscopic sinus surgery was performed. Histopathologically, the tumor cells exhibited an exophytic and endophytic growth pattern, composed of multilayered eosinophilic columnar epithelium with finely granular cytoplasm, and forming microcysts filled with mucin or microabscesses. The epithelium was PTAH-positive, and showed positivity for cytokeratin-7 with oncocytic features. A review of the literature revealed 166 cases of OSP in the nasal and paranasal sinuses, with an overall recurrence rate of about 15%. Here we report a case of OSP in the nasal and paranasal sinuses for which PTAH staining specific for oncocytes was useful, together with a review of the relevant literature.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"235-241"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Primary intraosseous squamous cell carcinoma with pagetoid spread arising in periapical odontogenic epithelium of the maxilla.","authors":"Shiho Hashiguchi, Ryosuke Kita, Aya Yoshino, Kaori Koga, Hiromasa Hasegawa, Makoto Hamasaki, Seiji Kondo","doi":"10.1007/s00795-024-00418-8","DOIUrl":"10.1007/s00795-024-00418-8","url":null,"abstract":"<p><p>To date, pagetoid spread-the proliferation of pagetoid cells in intraepidermal lesions, as observed in secondary extramammary Paget's disease-has not been reported in squamous epithelium derived from the extension of head and neck carcinomas. Herein, we report a case of pagetoid squamous cell proliferation associated with a primary intraosseous carcinoma (PIOC) arising in the periapical lesion of the maxilla, a finding not reported previously. A 60-year-old man presented with prostate adenocarcinoma and bilateral pubic bone, ilium bone, and sacral bone metastases. Radiological examination revealed a cyst that enveloped the apices of the left maxillary first molar roots. Histopathological examination of the cyst specimen indicated squamous cell carcinoma; hence, PIOC was suspected and partial left maxillectomy was performed. Histopathology results showed distant epitheliotrophic spread of atypical clear cells regarding the tumor. The epitheliotrophic cells were positive for cytokeratin (CK)19 and CK7 as odontogenic markers. These phenotypes were similar to those of tumor cells, suggesting pagetoid squamous cell proliferation associated with a PIOC arising. Although diagnosis of this condition is challenging, early detection is vital to ensure prompt treatment and improve patient prognosis.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"227-234"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The cross-talk between NRF2 and apoptosis in cancer.","authors":"Elmira Aboutalebi Vand Beilankouhi, Bahareh Yousefi, Niloofar Sadat Hadian, Reza Safaralizadeh, Mohammad Valilo","doi":"10.1007/s00795-025-00434-2","DOIUrl":"10.1007/s00795-025-00434-2","url":null,"abstract":"<p><p>Cancer is one of the common diseases that affects people in the society, the prevalence of which has decreased somewhat in recent years. Various genetic and environmental factors play a role in the development and progression of cancer. NRF2 is a transcriptional regulator that controls the expression of antioxidant response element-related genes. It plays an important role in regulating the physiological and pathophysiological consequences of oxidant exposure. NRF2 is also responsible for regulating the expression of various cellular protective genes. NRF2 activity is regulated at multiple levels including protein stability, transcription, and post-transcription. The Keap1-Cul3-Rbx1 axis is the most prominent regulator of NRF2 activity. Apoptosis is a type of programmed cell death that is initiated by two intrinsic and extrinsic pathways. Caspases play a major role in this cell death pathway. Apoptosis pathway is related to many cells signaling pathways that are interconnected. Disruption in one pathway affects the other pathway. One of these signaling pathways is the NRF2 pathway, which is associated with apoptosis, which are interconnected and play an important role in disease prevention or progression. Therefore, in this study, we decided to investigate the relationship between NRF2 and apoptosis in cancer.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"155-162"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Three-dimensional visualization of calcification during scale regeneration in goldfish.","authors":"Hisayuki Funahashi, Yusuke Maruyama, Nobuo Suzuki, Takashi Takaki, Kazuho Honda, Atsuhiko Hattori","doi":"10.1007/s00795-025-00427-1","DOIUrl":"10.1007/s00795-025-00427-1","url":null,"abstract":"<p><p>We used scanning electron microscopy to visualize the regeneration of goldfish scales on day 3 in vivo. Several vesicle-like structures of 100-700 nm diameter flowed onto the fibrous sheets in groups of spindle-shaped bodies arranged in the same direction. Transmission electron microscopy revealed that these structures were encircled by the lipid bilayer membrane. In addition, some had a small mass of high electron density. Scanning electron microscopic observations of specimens treated with bleach revealed particles of almost the same size as the observed electron-dense mass scattered between fibers, with a thickness of approximately 50 nm on day 3 of scale regeneration. The diameter of these particles increased by 5 times on day 14, sticking closely to the fibers. Furthermore, elemental analysis using electron probe microscopy showed that the particles were composed of calcium and phosphorous. These results confirmed that the spindle-shaped bodies and vesicle-like structures were osteoblasts and matrix vesicles, respectively.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"200-212"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role and potential mechanism of immunoglobulin G N-glycosylation in gastrointestinal tumors.","authors":"Yumeng Liu, Zejian Zhang, Xiequn Xu","doi":"10.1007/s00795-025-00448-w","DOIUrl":"https://doi.org/10.1007/s00795-025-00448-w","url":null,"abstract":"<p><p>Gastrointestinal tumors significantly contribute to cancer-related mortality worldwide. Early detection coupled with effective treatment significantly improves overall survival. Immunoglobulin G (IgG) N-glycosylation, a crucial post-translational modification, undergoes alterations in glycan structures. IgG N-glycosylation is associated with numerous physiological and pathological processes in the human body. Aberrant changes of IgG N-glycosylation play a key role in cancers given the involvement of glycans in cancer progression and immune modulation. These changes affect the binding of the Fc region of IgG to its receptor, in turn, affect the corresponding downstream effects, which are crucial in cancer immuno-surveillance and immune escape. This review aims to explore the latest advancements in understanding IgG N-glycosylation in gastrointestinal cancers, emphasizing its potential as a diagnostic biomarker and therapeutic target. The application of IgG N-glycosylation in clinical oncology could enhance early detection, improve therapeutic efficacy, and enable better monitoring of disease progression and recurrence. Furthermore, we summarized the research progression to provide novel insights into the potential regulatory mechanism of IgG N-glycosylation in gastrointestinal tumors. In all, IgG N-glycosylation holds significant promise for advancing cancer diagnosis and treatment. Further studies are required to fully elucidate its mechanisms and optimize its use in clinical practice.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}