Okada H, Hayashi Y, Furukawa N
… +7 more, Bunno Y, Yamamoto M, Miyazaki R, Iguchi M, Toi M, Murakami I, Tamura M
Med Mol Morphol
· 2026 Mar · PMID 40888887
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Fascin-1, an actin-bundling protein, plays a crucial role in cancer cell motility, invasion, and epithelial-mesenchymal transition (EMT). While its significance has been demonstrated in several malignancies, its clinical...Fascin-1, an actin-bundling protein, plays a crucial role in cancer cell motility, invasion, and epithelial-mesenchymal transition (EMT). While its significance has been demonstrated in several malignancies, its clinical relevance in thymic carcinoma remains unclear. We retrospectively analyzed 10 surgically resected thymic carcinoma cases treated at Kochi University Hospital from 2008 to 2024. Immunohistochemical staining was performed to evaluate Fascin-1 expression using the Allred scoring system. Expression of EMT-related markers (TGF-β, pSmad3, Snail, and E-cadherin) was also assessed. Associations between Fascin-1 expression and postoperative recurrence were analyzed. Fascin-1 was highly expressed in tumor regions with low E-cadherin expression and co-localized with EMT-inducing markers such as TGF-β and Snail. Patients with postoperative recurrence showed significantly higher Fascin-1 scores than those without recurrence (P = 0.048). Double immunofluorescence confirmed an inverse relationship between Fascin-1 and E-cadherin expression. High Fascin-1 expression may serve as a potential marker for postoperative recurrence in thymic carcinoma and is closely associated with EMT. These findings suggest Fascin-1 as a promising prognostic biomarker and therapeutic target, although further studies with larger cohorts and functional analyses are warranted.
Med Mol Morphol
· 2025 Dec · PMID 40853398
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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...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.
Oyama Y, Furukawa-Kubota R, Kadowaki H
… +4 more, Wada J, Kawamura K, Miura T, Daa T
Med Mol Morphol
· 2026 Mar · PMID 40781209
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This report presents the sixth case of chest wall epithelioid sarcoma (ES) in a 71-year-old Japanese man. The patient was incidentally diagnosed with a soft tissue tumor between the eighth and ninth ribs, presenting with...This report presents the sixth case of chest wall epithelioid sarcoma (ES) in a 71-year-old Japanese man. The patient was incidentally diagnosed with a soft tissue tumor between the eighth and ninth ribs, presenting with an associated bone fracture and osteolytic change. Marginal resection followed by chest wall reconstruction was performed for a definitive diagnosis. Histopathological examination revealed multinodular growth associated with collagenous stroma, mimicking a necrotizing granulomatous process. Various tumor cells were observed, including epithelioid, spindle-shaped, and rhabdoid cells. Immunohistochemical analysis, conducted on trimmed tumor samples without decalcification, revealed positivity for cytokeratin AE1/AE3, vimentin, and CD34, as well as negativity for CK7, CK20, CD31, calretinin, and D2-40. INI expression was completely absent in tumor cells. The patient was diagnosed with ES. The chest wall is an unusual location for ES, and its diagnosis requires differentiation from other epithelioid neoplasms. This case highlights the importance of trimming tumor samples before decalcification to preserve antigenicity and ensure accurate immunohistochemistry analysis.
Yukino K, Komohara Y, Zhao S
… +6 more, Yamada R, Fujiwara Y, Murakami A, Shimoda Y, Saito H, Orita Y
Med Mol Morphol
· 2026 Mar · PMID 40705032
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Anaplastic thyroid carcinoma (ATC) is a highly aggressive neoplasm with no effective treatment options. ATC with osteoclast-like giant cells (OGCs; ATC/OGC) is a rare variant of ATC, and no detailed pathological examinat...Anaplastic thyroid carcinoma (ATC) is a highly aggressive neoplasm with no effective treatment options. ATC with osteoclast-like giant cells (OGCs; ATC/OGC) is a rare variant of ATC, and no detailed pathological examination has been reported to date. A 59-year-old woman presented with sudden neck swelling. Computed tomography revealed a 5 cm tumor in the thyroid gland, which was surgically resected. Pathological examination revealed a diagnosis of ATC/OGC. The patient succumbed to progressive lung metastases within four months despite postoperative lenvatinib therapy. Immunohistochemical (IHC) examination indicated absence of PD-L1 expression in the OGCs, which comprised the majority of the tumor, with only sparse T cell infiltration in the area occupied by OGCs. Increased TGF-β expression was observed in the area containing OGCs, and both OGCs and infiltrating myeloid cells, including CD1a/CD11c-positive dendritic cells and CD68/CD163/CD204-positive macrophages, appeared to produce TGF-β. Pathological analysis of this case suggests that OGCs might be involved in immune suppression by secreting TGF-β, potentially serving as a critical cytokine in the immunosuppressive microenvironment of ATC/OGC. TGF-β-targeted therapy might be useful in the treatment of this very rare subtype of ATC.
Bolortsetseg D, Kurashige Y, Mielnik-Błaszczak M
… +7 more, Islam ST, Fujita Y, Sakakibara S, Minowa E, Yoshimoto H, Abiko Y, Saitoh M
Med Mol Morphol
· 2026 Mar · PMID 40622416
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We have previously isolated the epithelial rests of Malassez (ERM) clone cells with strong Amelx expression, named as ERM-2, from the crude ERM cells. In the present study, we examined whether conditioned medium (CM) der...We have previously isolated the epithelial rests of Malassez (ERM) clone cells with strong Amelx expression, named as ERM-2, from the crude ERM cells. In the present study, we examined whether conditioned medium (CM) derived from cultured ERM-2 promotes the crystallization of immature enamel in tooth germs. Tooth germs from postnatal day 3 mice were incubated with ERM-2 conditional medium (CM). ERM-2 cells were transfected with si-RNA targeting specific enamel matrix proteins (EMPs). After 2 days of incubation, each CM was collected and employed to culture the tooth germs. The surface layers of the enamel structure were examined with a scanning electron microscope (SEM). Tooth germs cultured with ERM-2 CM on days 3 and 7 showed elongation and densification of the columnar structures in SEM analysis. The columnar structures became denser and aggregated forming a HAP-like hexagonal columnar structure 14 days after culture in ERM-2 CM. In contrast, no clear columnar structures were observed in ERM-2 CM with si-RNA of each EMPs. In conclusion, the present study demonstrated that CM derived from ERM-2 could form enamel-like structures on the surface of the tooth germ. ERM-2 may provide the possibility for the clinical use of enamel regeneration.
Deguchi T, Tanaka H, Horioka K
… +8 more, Matsuhisa C, Hayakawa A, Takauji S, Watanabe S, Goto M, Fujii Y, Takasawa K, Takasawa A
Med Mol Morphol
· 2026 Mar · PMID 40601028
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Global warming has increased summer temperatures, leading to a rise in heat stroke-related deaths in Japan. Heat stroke disrupts the body's adaptation to high temperatures, often resulting in severe complications, includ...Global warming has increased summer temperatures, leading to a rise in heat stroke-related deaths in Japan. Heat stroke disrupts the body's adaptation to high temperatures, often resulting in severe complications, including liver damage and even death. However, despite the increasing incidence, pathological autopsies remain rare, and the histological changes associated with heat stroke are poorly understood. In this study, we investigated the pathogenesis of heat stroke using a mouse model. Mice were exposed to 45 °C for 30 min and dissected immediately or 24, 48, and 72 h post-exposure. Histological analysis revealed significant lipid accumulation in hepatocytes surrounding the central vein at 24, 48, and 72 h. At 24 h, hepatocytes also exhibited features of early degeneration, including cytoplasmic lysis and chromatin condensation. Lipidomics analysis of liver tissue collected 24 h post-exposure demonstrated a marked increase in 27-hydroxycholesterol levels. These results indicate that heat stress rapidly disrupts hepatic lipid homeostasis, causing cellular damage and metabolic remodeling. The observed lipid accumulation, including elevated 27-hydroxycholesterol, may play dual roles in mediating inflammation and serving as a protective response. Our findings provide new insight into the pathogenesis of heat stroke-induced liver injury and suggest potential molecular targets for early diagnosis and intervention.
Aksin M, Ates KE, Mirioglu A
… +2 more, Toyran T, Gonlusen G
Med Mol Morphol
· 2026 Mar · PMID 40560238
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Soft tissue sarcomas are heterogenous groups of tumors that show variable morphology as well as clinical behavior. Morphological features do not always directly reflect clinical behavior. Certain mesenchymal tumors exhib...Soft tissue sarcomas are heterogenous groups of tumors that show variable morphology as well as clinical behavior. Morphological features do not always directly reflect clinical behavior. Certain mesenchymal tumors exhibit an indolent clinical course. Among them are superficial CD34-positive fibroblastic tumors characterized by PRDM10 fusion. In our study, we aimed to detect PRDM10 gene rearrangement in superficial CD34-positive fibroblastic tumors and other pleomorphic sarcomas included in its differential diagnosis by immunohistochemistry and Fluorescence in situ hybridization. Totally, 33 cases were enrolled into this study. The results showed that two cases diagnosed as superficial CD34-positive fibroblastic tumor and two cases diagnosed as undifferentiated pleomorphic sarcoma have PRDM10 gene rearrangement. Immunohistochemically, not all rearranged tumors showed PRDM10 staining that suggests a low sensitivity of PRDM10 antibody. In conclusion, we suggested that PRDM10 gene rearrangement is not limited to superficial CD34-positive fibroblastic tumors; undifferentiated pleomorphic sarcomas may exhibit this molecular alteration and immunohistochemistry has lower sensitivity than fluorescence in situ hybridization.
Beppu A, Miyaaki H, Miuma S
… +9 more, Sasaki R, Haraguchi M, Fukusima M, Nakao Y, Tajima K, Matsuo S, Akazawa Y, Okano S, Nakao K
Med Mol Morphol
· 2026 Mar · PMID 40471345
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This study aimed to investigate carcinogenesis-related fibrosis patterns in liver biopsy tissues from patients with metabolic dysfunction-associated steatotic liver disease (MASLD) by comprehensively measuring and quanti...This study aimed to investigate carcinogenesis-related fibrosis patterns in liver biopsy tissues from patients with metabolic dysfunction-associated steatotic liver disease (MASLD) by comprehensively measuring and quantifying various fibrosis patterns using artificial intelligence. Liver biopsy tissues from 13 patients with advanced fibrosis at MASLD diagnosis were subjected to collagen quantification and morphological and structural fiber characteristic evaluation using FibroNest (PharmaNest, Princeton, NJ, USA), which was described using up to seven quantitative fibrosis parameters (qFPs). The collagen-fibrosis composite score (FCS), morphometric-FCS, architecture-FCS, and phenotypic-FCS (Ph-FCS) were compared between patients with and without hepatocellular carcinoma (HCC). The collagen quantification alone could not discriminate between HCC and non-HCC cases. Regarding the individual qFPs of morphological fiber characteristics, the kurtosis and skewness of fiber twists were significantly lower in HCC cases than in non-HCC cases. In HCC cases, fiber width and density kurtosis tended to be larger, whereas fiber length kurtosis tended to be smaller than those in non-HCC cases. Ph-FCS could discriminate HCC from non-HCC at a threshold of 4.2, with 85% sensitivity and 100% specificity. A combination of fiber morphology and structural characteristics predicted HCC development with higher accuracy and might help define carcinogenic risk groups among patients with MASLD.
Kawano H, Kawamura K, Maemura K
… +1 more, Okano S
Med Mol Morphol
· 2025 Dec · PMID 40295313
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A 29-year-old Japanese woman was admitted to our hospital with fever, cardiogenic shock, and cardiac arrest and died 18 h after admission. The patient was diagnosed with systemic capillary leak syndrome associated with c...A 29-year-old Japanese woman was admitted to our hospital with fever, cardiogenic shock, and cardiac arrest and died 18 h after admission. The patient was diagnosed with systemic capillary leak syndrome associated with coronavirus disease 2019. Electron microscopy of the biopsied right-ventricular myocardium revealed extensive interstitial leakage of blood cells and plasma, damaged capillaries, and reticular vessel drainage into the Thebesian vein. These findings indicate that severe capillary leak and lumen occlusion due to damaged capillaries are the main features of systemic capillary leak syndrome.
Fujiki Y, Ishikawa A, Katsuya N
… +9 more, Shiwa Y, Fukui T, Kuraoka K, Sudo T, Tazuma S, Ishii Y, Oka S, Yasui W, Mii S
Med Mol Morphol
· 2026 Mar · PMID 40293517
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most well-known cancer types, with a persistently poor 5-year survival rate. We previously reported MCM4 as a molecule associated with cancer stem cells; however, its...Pancreatic ductal adenocarcinoma (PDAC) is one of the most well-known cancer types, with a persistently poor 5-year survival rate. We previously reported MCM4 as a molecule associated with cancer stem cells; however, its role in PDAC has not been reported. Therefore, in this study, we aimed to fill this gap in the literature. We analyzed MCM4 expression in 81 PDAC samples using immunohistochemistry (IHC). The functional role of MCM4 in PDAC was investigated using RNA interference in PDAC cell lines. Additionally, a single-cell analysis was conducted by downloading data from six PDAC cases. On IHC, high MCM4 expression was observed in 42 out of 81 (51.9%) PDAC cases. MCM4-positive PDAC was significantly associated with a higher pN grade. Furthermore, high MCM4 expression was linked to a significantly poorer prognosis and was identified as an independent prognostic factor in multivariate analysis. In PDAC cell lines, MCM4 knockdown impairs cell growth and spheroid formation. Single-cell analysis also revealed that MCM4-expressing cells were located upstream of the trajectory, with a cluster showing a correlation with KIFC1, which has been reported to be associated with cancer stemness. These results indicated the significance of MCM4 expression in PDAC and its association with cancer stemness.
Med Mol Morphol
· 2025 Dec · PMID 40237837
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BACKGROUND: With the extensive application of flap surgery in clinical practice, it has been a matter of great concern to improve the survival rate of flap surgery for a long time. This study compared and explored the ef...BACKGROUND: With the extensive application of flap surgery in clinical practice, it has been a matter of great concern to improve the survival rate of flap surgery for a long time. This study compared and explored the effect of the three generations of platelet concentrates (PCs), including platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor (CGF), on flap survival. METHODS: After PRP, PRF, and CGF gels were observed by scanning electron microscope (SEM), their vascularizing effect were assessed by infrared thermal imager, flap survival experiment, arterial perfusion angiography, and immunohistochemical staining in a rat dorsal cross-region perforator flap model. RESULTS: The fibrin of PRP gel showed irregular clumps and loose structure, while that of PRF and CGF gels formed 3D network structure with orderly arrangement and compact structure. In animal models, the use of all the three PCs can increase the number of vessels and the amount of blood perfusion in choke zones (all P < 0.05), thus improving the flap survival rate. Moreover, the effects of CGF and PRF were obviously better than those of PRP (all P < 0.05), but there was no significant difference between CGF and PRF (P > 0.05). CONCLUSIONS: PRP, PRF, and CGF all have a good effect on promoting vascularization, and can significantly improve the survival rate of dorsal cross-region perforator flap in rat model. Besides, PRF and CGF have greater potential in promoting vascularization than PRP.
Kojima K, Sakurai K, Ando T
… +4 more, Sakai Y, Ochiai M, Kato T, Ito H
Med Mol Morphol
· 2026 Mar · PMID 40234276
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Prospero homeobox protein 1 (PROX1) is aberrantly expressed in tumors, including neuroendocrine neoplasms (NENs); however, the detailed expression pattern remains elusive. This study aimed to immunohistochemically assess...Prospero homeobox protein 1 (PROX1) is aberrantly expressed in tumors, including neuroendocrine neoplasms (NENs); however, the detailed expression pattern remains elusive. This study aimed to immunohistochemically assess PROX1 expression. Immunohistochemistry (IHC) for PROX1 was performed on tissue microarrays of normal tissues (n = 107), NENs (n = 152) (small cell lung carcinoma [SCLC], lung carcinoid [LC], gastroenteropancreatic-NEN [GEP-NEN], esophageal neuroendocrine carcinoma [ENEC], medullary thyroid carcinoma [MTC], neuroblastoma [NB], and pheochromocytoma [PHEO]), and non-NENs (n = 469). In normal tissues, PROX1 was expressed in lymphatic endothelial cells and a subset of epithelial cells in the gastrointestinal tract and the distal convoluted tubules. In NENs, the positive expression was observed in the nucleus of tumor cells in 19/26 SCLC (73.1%), 13/16 LC (81.3%), 10/15 GEP-NEN (66.7%), 2/2 ENEC (100%), 17/43 MTC (39.5%), 1/25 NB (4.0%), and 0/25 PHEO (0%). Although PROX1 was negative in many non-NENs, our analysis revealed high expression in certain cases with medulloblastoma and one case with juvenile granulosa cell tumor. PROX1 was expressed in specific cases with epithelial NENs and some cases with non-NENs. Analysis of PROX1 should provide insights into the molecular characteristics of distinct tumors.
Shichi Y, Fujiwara M, Gomi F
… +7 more, Nonaka K, Hasegawa F, Shinji S, Rokutan H, Arai T, Takahashi K, Ishiwata T
Med Mol Morphol
· 2025 Dec · PMID 40183819
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Pancreatic ductal adenocarcinoma (PDAC) cell lines are classified into two types: epithelial and mesenchymal protein-expressing. Using scanning electron microscopy, we reported that these two groups differ in terms of mo...Pancreatic ductal adenocarcinoma (PDAC) cell lines are classified into two types: epithelial and mesenchymal protein-expressing. Using scanning electron microscopy, we reported that these two groups differ in terms of morphology when they formed tumor spheres under three-dimensional (3D) culturing. In this study, we used transmission electron microscopy (TEM) to examine the intracellular microstructures of five epithelial and three mesenchymal PDAC cell lines in 3D culture, and compared them to the morphologies of the same cell types in two-dimensional (2D) cultures. Microvilli were present in all PDAC cells cultured in 2D and 3D, and were well developed in epithelial PDAC cells. Desmosome-like structures were only observed in epithelial PDAC cells, and were more common in 3D cultures. Secretory granules were observed in epithelial PDAC and mesenchymal PANC-1 cells, and were more common in 3D cultures. Intracytoplasmic lumina were only observed in epithelial PK-59 and T3M-4 cells cultured in 3D. Abundant filamentous aggregates were observed in 2D-cultured T3M-4 and MIA PaCa-2 cells. By contrast, entosis was observed in 3D-cultured PK-59, PK-1, and KP4 cells. Microstructural differences enhanced by 3D culturing revealed significant phenotypic diversity among PDAC cells, and may provide key insights into curing intractable pancreatic cancer.
Ibe Y, Ozaki Y, Anami T
… +9 more, Yano H, Fujiwara Y, Nishizawa H, Kurahashi R, Motoshima T, Murakami Y, Yatsuda J, Komohara Y, Kamba T
Med Mol Morphol
· 2025 Dec · PMID 40126633
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The number of patients with prostate cancer has been increasing around the world. Although anticancer immunotherapy targeting the immune checkpoint molecules has been approved for many types of cancer, no significant ant...The number of patients with prostate cancer has been increasing around the world. Although anticancer immunotherapy targeting the immune checkpoint molecules has been approved for many types of cancer, no significant anti-cancer effects have been observed in patients with prostate cancer. Lymph node sinus macrophages (LSMs) are known to work as antigen-presenting cells, which are critical for anticancer immune responses. Previous studies have suggested that CD169 expression in LSMs affects anticancer immune responses in several cancers, including prostate cancer. In the present study, we aimed to examine the correlation between the tumor immune microenvironment and activation status of LSMs in patients with prostate cancer. Forty-two cases of high-risk localized prostate cancer treated using robot-assisted laparoscopic radical prostatectomy and lymph node dissection between 2017 and 2021 were enrolled. CD169 expression in LSMs was examined by immunohistochemistry. The results indicated that CD169 expression in LSMs was significantly decreased in older (≥ 75 years) compared with younger patients. However, no significant correlation was found between CD169 expression and any other clinicopathological factors. In addition, CD3- and CD8-postitive lymphocytes in primary cancer tissues were evaluated in the same cases, and their correlations with CD169 expression in LSMs were tested. Although these lymphocytes tended to be higher in CD169 than in CD169 cases, the difference was not statistically significant. In conclusion, we found that CD169 expression was upregulated in older patients and tended to be related to T cell infiltration in cancer tissues. Therefore, the downregulation of CD169 in LSMs might be involved in the reduced anticancer immune response in prostate cancer.
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 progre...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.
Med Mol Morphol
· 2025 Dec · PMID 40102227
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The placenta is the most critical organ during pregnancy and its developmental status directly impacts fetal health. Placental dysfunction is associated with various pregnancy complications, including preterm birth, feta...The placenta is the most critical organ during pregnancy and its developmental status directly impacts fetal health. Placental dysfunction is associated with various pregnancy complications, including preterm birth, fetal growth restriction, and premature rupture of membranes (PROM). This study aimed to elucidate the expression changes of Bax and Bcl-2 and their association with pregnancy-related complications, providing new insights into placental dysfunction during pregnancy and offering a theoretical foundation for clinical diagnosis and prevention. The placental samples from 118 late pregnant women were retrospectively analyzed. They were assigned into pre-term, term, post-term, PROM, and non-PROM groups based on gestational age and the occurrence of PROM. Immunohistochemistry (IHC) staining was performed to gauge the Bax and Bcl-2 expressions in placenta. Receiver operating characteristic (ROC) curve was subsequently conducted to assess their associated with efficacy for PROM. The weight and volume of placentas in the pre-term group were sharply smaller to those in the term and post-term groups, with no apparent fibrosis or calcification observed. The term and post-term groups exhibited marked elevated Bax expression in the parturient group in contrast to the non-parturient group (P < 0.05), while there existed no substantial significance in Bcl-2 expression. The area under the curve (AUC) for Bax and Bcl-2 was 0.975 and 0.596, respectively, with a combined associated with value of 0.978, higher to single predictions. Bax and Bcl-2 expressions in late pregnancy placentas were associated with the onset of parturient status and PROM and their combined prediction exhibited accurate PROM predicted. These findings offered a new perspective for understanding the physiological and pathological changes of the placenta during pregnancy.
Yamaguchi T, Takamura M, Tochigi H
… +8 more, Mizuno Y, Mizuno Y, Sato T, Tamaru S, Kusama K, Tamura K, Kamei Y, Kajihara T
Med Mol Morphol
· 2025 Dec · PMID 40085209
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This study aims to investigate the function of miR-424 and miR-503, identified as putative regulatory miRNAs of FOXO1, a key factor for decidualization. The expression of both miR-424 and miR-503 in human endometrial str...This study aims to investigate the function of miR-424 and miR-503, identified as putative regulatory miRNAs of FOXO1, a key factor for decidualization. The expression of both miR-424 and miR-503 in human endometrial stromal cells (HESCs) were measured before and after decidualization. Then, HESCs were transfected with both miR-424 and miR-503 before decidualization. Quantitative reverse transcription PCR, actin staining analysis, migration assay, fluorescence immunostaining, and luciferase assay were performed. MiR-424 and miR-503 expression was decreased after decidualization. Overexpression of both miR-424 and miR-503 inhibited major decidual maker genes, including FOXO1, PRL, IGFBP1, WNT4, and SCARA5, and altered F-actin's subcellular distribution from the periphery to all over the cytoplasm, concomitantly increasing cell mobility. Moreover, immunohistochemical analysis revealed overexpression of both miRNAs resulted in FOXO1 protein accumulation in the cytoplasm. Knocking down FOXO1 decreased SCARA5 expression, revealing SCARA5 is a downstream target of FOXO1. In addition, a luciferase reporter assay confirmed that the 3'-untranslated region of FOXO1 mRNA is targeted by miR-424. These results suggest that both miRNAs may play an important role in endometrial decidualization by regulating transcriptional activity of FOXO1, which alters decidualization-related gene expression such as SCARA5.Abstract: Journal standard instruction requires an unstructured abstract; hence structured abstract changed to unstructured.Thank you for the correction. I approve this change.
Kashiwagi H, Shigehara K, Kubo T
… +11 more, Hirohashi Y, Mariya T, Matsuo K, Minowa T, Ishioka SI, Murata K, Kanaseki T, Tsukahara T, Hasegawa T, Saito T, Torigoe T
Med Mol Morphol
· 2025 Dec · PMID 40082293
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Placenta accreta spectrum (PAS) is a serious disease leading to complications and maternal death. The objective of the study was to characterize the placental villi and blood vessels of PAS villi histopathologically. We...Placenta accreta spectrum (PAS) is a serious disease leading to complications and maternal death. The objective of the study was to characterize the placental villi and blood vessels of PAS villi histopathologically. We investigated 10 cases of PAS (five cases of placenta increta, two cases of placenta accreta, and three cases of placenta percreta) histologically. Immunohistochemical staining using anti-CD68 or anti-CD163 antibodies was performed to detect and count Hofbauer cells. Immunohistochemical staining with an anti-CD34 antibody was used to detect vascular endothelial cells, and the number and area of vessels were analyzed. The numbers of CD68-positive or CD163-positive Hofbauer cells were larger in PAS cases compared with control cases. The vascular area in villi was smaller in PAS cases compared with control cases. The number of blood vessels in villi was slightly higher in PAS cases than in control cases. The numbers of Hofbauer cells and vessels in villi were larger in PAS cases compared with control cases, whereas the area of vessels in villi was smaller in PAS cases compared with control cases. Although their biological meaning is elusive, these findings provide novel insights into the pathogenesis of PAS, particularly regarding the role of Hofbauer cells in immune-suppressive role and angiogenesis and the alterations in vascular structure and hemodynamics in the chorionic villi.
Shirakawa K, Nakazato R, Hara T
… +4 more, Uemura K, Ijaz F, Takahashi S, Ikegami K
Med Mol Morphol
· 2025 Sep · PMID 40069423
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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 duct...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.