{"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":1.4,"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":"Novel orthotopic patient-derived xenograft model using human pancreatic cancer tissue fragments to recapitulate distant metastasis and cancer-related hypercoagulability.","authors":"Takuma Miura, Arisa Watanabe, Mutsumi Miyake, Sayaka Suga, Makoto Miyoshi, Kumiko Miyashita, Shohei Komatsu, Noriyuki Nishimura, Kazuya Shimizu, Yuichi Hori","doi":"10.1007/s00795-025-00425-3","DOIUrl":"10.1007/s00795-025-00425-3","url":null,"abstract":"<p><p>Pancreatic cancer is a malignant tumor that metastasizes to distant organs, such as the liver and lungs from an early stage. Few animal models can reproduce early metastasis. In addition, no model has been reported that reproduces cancer-related hypercoagulability, which is characteristic of pancreatic ductal adenocarcinoma and other adenocarcinomas. We hypothesized that the reason why the commonly used orthotopic cell xenograft model cannot reproduce the disease is inadequate construction of the cancer microenvironment. We developed an orthotopic tissue fragment xenograft model in which tumor tissue was transplanted into the pancreas of mice while preserving the microenvironment. Briefly, we injected single cancer cells subcutaneously to form a tumor, which was then cut with a scalpel into tumor fragments. A fragment was then sutured and fixed to the surface of the pancreatic tail. In this study, we evaluated the superiority of this model over a conventional orthotopic cell xenograft model. As a result, the novel orthotopic tissue xenograft model reproduced early distant metastasis to the liver and lung, nerve invasion, and cancer-related hypercoagulability of human pancreatic cancer, and showed greater similarity to clinical cases than the control orthotopic cell xenograft model.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"183-192"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597272","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":"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":"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":1.4,"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":"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":1.4,"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":"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":1.4,"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":1.4,"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 relation in MreB and intrabacterial nanotransportation system for VacA in Helicobacter pylori.","authors":"Hong Wu, Yoshihiko Fujioka, Noritaka Iwai, Shoichi Sakaguchi, Youichi Suzuki, Takashi Nakano","doi":"10.1007/s00795-024-00416-w","DOIUrl":"10.1007/s00795-024-00416-w","url":null,"abstract":"<p><p>Helicobacter pylori possesses an intrabacterial nanotransportation system (ibNoTS) for transporting VacA, CagA, and urease within the bacterial cytoplasm. This system is controlled by the extrabacterial environment. The transport routes of the system for VacA have not yet been studied in detail. In this study, we demonstrated by immunoelectron microscopy that VacA localizes closely with the MreB filament in the bacterium, and the MreB polymerization inhibitor A22 obstructs the transport of VacA by ibNoTS. These findings indicate that the route of ibNoTS for VacA is closely associated with the MreB filament Additionally, it was confirmed that VacA does not closely associate with the bacterial filament FtsZ, which is involved in the transport of the virulence factor urease, as previously suggested. We propose that the route of ibNoTS for VacA is associated with the MreB filament in H. pylori.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"126-136"},"PeriodicalIF":1.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864841","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}
Ko Yamagata, Yousuke Mizuno, Yumi Mizuno, Shunnsuke Tamaru, Takeshi Kajihara
{"title":"Androgens modulate endometrial function.","authors":"Ko Yamagata, Yousuke Mizuno, Yumi Mizuno, Shunnsuke Tamaru, Takeshi Kajihara","doi":"10.1007/s00795-025-00430-6","DOIUrl":"10.1007/s00795-025-00430-6","url":null,"abstract":"<p><p>Human endometrium is the major target tissue for sex steroid hormones. The circulating steroid hormones in normal ovulatory cycles accurately control the proliferation and differentiation of the endometrial cells. Androgens, such as testosterone and 5α-dihydrotestosterone, are a type of sex steroid hormones that mainly function in the differentiation, development, and maintenance of male sexual characteristics. Although androgens are best known for their role in male reproduction, the androgen receptor is present in both male and female reproductive organs and is essential for normal reproductive function. Recently, a series of evidence suggests that androgens contribute to endometrial physiology and pathologies. However, the roles of androgens in the endometrium remain insufficiently understood, with contradictory findings being reported. This review summarizes the studies that show the role of androgens in regulating the physiological conditions of the endometrium and the implantation process, and endometrial pathology including endometriosis and others.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"93-99"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597270","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":"Clinicopathological significance of sulfite oxidase expression in surgically resected lung adenocarcinoma.","authors":"Saeko Tokisawa, Reiichiro Kondo, Masamichi Nakayama, Sachiko Ogasawara, Kenta Murotani, Masahiro Mitsuoka, Tomoaki Hoshino, Hirohisa Yano, Jun Akiba","doi":"10.1007/s00795-024-00413-z","DOIUrl":"10.1007/s00795-024-00413-z","url":null,"abstract":"<p><strong>Aim: </strong>The coenzyme sulfite oxidase (SUOX), located in mitochondria, plays a role in redox and metabolism. Its expression has been associated with cancer progression and prognosis. Lung cancer has a high incidence rate and poor prognosis. We aim to clarify its expression in lung adenocarcinomas and investigated the utility of SUOX expression as a recurrence factor in operable lung adenocarcinoma.</p><p><strong>Methods: </strong>We used 60 formalin-fixed paraffin-embedded samples of operable primary lung adenocarcinoma between 2017 and 2018 to immunohistochemically assess SUOX expression levels. Patients were classified into a high or low SUOX expression group, and the associations of SUOX expression with clinicopathological findings and recurrence were analyzed.</p><p><strong>Results: </strong>We revealed that high SUOX expression was significantly (p < 0.05) associated with sex, low Brinkman index, histological type, histological grade and positive for epidermal growth factor receptor (EGFR) mutation. High SUOX expression (HR = 10.218, 95% CI 1.758‒59.376, p = 0.0096) and pathological Stage (HR = 7.538, 95% CI 1.95‒29.14, p = 0.0034) were independently associated with relapse free survival.</p><p><strong>Conclusion: </strong>High SUOX expression may be a new indicator of recurrence risk in surgically resected lung adenocarcinomas.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"106-113"},"PeriodicalIF":1.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801492","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}