{"title":"Elevated expression of endocan in the development of cervical squamous neoplasia of the uterus.","authors":"Midori Sato, Ayano Inoue, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara, Makoto Osanai","doi":"10.1007/s00795-023-00353-0","DOIUrl":"10.1007/s00795-023-00353-0","url":null,"abstract":"<p><p>Accumulated evidence has shown that endocan, which was originally called endothelial cell-specific molecule-1, is an attractive prognostic factor in a variety of cancers. However, the relevance of endocan expression in human malignancies remains to be clarified. In the present study, the expression of endocan in cervical squamous neoplasia of the uterus, including low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), as well as in invasive squamous cell carcinoma was examined by immunohistochemistry. Endocan was not sufficiently expressed in the normal cervical epithelium. Endocan expression was present in LSIL cases but was limited to basal and parabasal areas of the cells. HSIL cases exhibited strong expression of endocan with widely distributed expression toward the epithelial surface. In contrast, further strong expression of endocan was not observed in patients with invasive carcinoma. This study is the first study showing increased expression of endocan in precancerous dysplastic lesions and malignancy of the cervix. The data suggest that a high expression level of endocan potentially contributes to the development of cervical squamous neoplasia of the uterus.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10038008","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":"Altered microbiota caused by disordered gut motility leads to an overactivation of intestinal immune system in APC1638T mice.","authors":"Nami O Yamada, Wenduerma, Takao Senda","doi":"10.1007/s00795-023-00352-1","DOIUrl":"10.1007/s00795-023-00352-1","url":null,"abstract":"<p><p>Adenomatous polyposis coli (APC) is recognized as an antioncogene related to familial adenomatous polyposis and colorectal cancers. However, APC is a large protein with multiple binding partners, indicating APC has diverse roles besides as a tumor suppressor. We have ever studied the roles of APC by using APC<sup>1638T/1638T</sup> (APC1638T) mice. Through those studies, we have noticed stools of APC1638T mice were smaller than those of APC<sup>+/+</sup> mice and hypothesized there be a disturbance in fecal formation processes in APC1638T mice. The gut motility was morphologically analyzed by immunohistochemical staining of the Auerbach's plexus. Gut microbiota was analyzed by terminal restriction fragment length polymorphism (T-RFLP). IgA concentration in stools was determined by enzyme-linked immunosorbent assay (ELISA). As results, macroscopic findings suggestive of large intestinal dysmotility and microscopic findings of disorganization and inflammation of the plexus were obtained in APC1638T mice. An alteration of microbiota composition, especially increased Bacteroidetes population was observed. Increases in IgA positive cells and dendritic cells in the ileum with high fecal IgA concentration were also confirmed, suggesting over-activation of gut immunity. Our findings will contribute to our understanding of APC's functions in the gastrointestinal motility, and lead to a development of novel therapies for gut dysmotility-related diseases.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10322834","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":"Iron overload due to SLC40A1 mutation of type 4 hereditary hemochromatosis.","authors":"Jing Hu, Yuan Li, Li Zhang, Guangxin Peng, Fengkui Zhang, Xin Zhao","doi":"10.1007/s00795-023-00359-8","DOIUrl":"10.1007/s00795-023-00359-8","url":null,"abstract":"<p><p>Hereditary hemochromatosis type 4 is an autosomal-dominant inherited disease characterized by a mutation in the SLC40A1 gene encoding ferroportin. This condition can be further subdivided into types 4A (loss-of-function mutations) and 4B (gain-of-function mutations). To date, only a few cases of type 4B cases have been reported, and the treatment has not been clearly mentioned. Here, we report a genotype of hereditary hemochromatosis type 4B involving the heterozygous mutation c.997 T > C (p. Tyr333His) in SLC40A1. The patient was treated with red blood cell apheresis every month for 1 year, followed by oral deferasirox, and the combined therapy was found to be effective.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10323834","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":"Direct observation of epoxy resin blocks for renal biopsy by low-vacuum scanning electron microscopy.","authors":"Akihiro Tojo, Makoto Abe, Kin-Ichi Matsuyama","doi":"10.1007/s00795-023-00356-x","DOIUrl":"10.1007/s00795-023-00356-x","url":null,"abstract":"<p><p>To improve the resolution of low-vacuum scanning electron microscopy (LVSEM), the epoxy resin block for the transmission electron microscopy (TEM) was observed directly with LVSEM. After observing ultrathin sections from renal biopsies of IgA nephropathy, membranous nephropathy, lupus nephritis, diabetic nephropathy (DM), thin basement membrane disease (TBMD), Alport's syndrome, Fabry's disease, and renal amyloidosis, the epoxy resin blocks of the same sites were observed by LVSEM and compared. The LVSEM image of the epoxy resin block corresponds to the negative of the TEM image, and when the gradation is reversed, the LVSEM image was comparable to the TEM image. At a low magnification of 100 ×, the entire specimen, including the glomerulus, was obtained. LVSEM at 5000 × magnification was sufficient to identify paramesangial deposits in IgA nephropathy and subepithelial electron-dense deposits (EDD) and spikes in membranous nephropathy. Glomerular basement membrane thickening in DM and thinning in TBMD could be sufficiently diagnosed with LVSEM at 6000 ×. Accumulation of ceramide in Fabry's disease was easily identified, but amyloid fibril could not be identified by LVSEM. LVSEM of renal biopsy epoxy resin blocks can replace TEM up to moderate magnification.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9981593","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":"Regaining enamel color quality using enamel matrix derivative.","authors":"Hiroyuki Sugaya, Yoshihito Kurashige, Kai Suzuki, Sayaka Sakakibara, Yusuke Fujita, Syed Taufiqul Islam, Takashi Nezu, Shuichi Ito, Yoshihiro Abiko, Masato Saitoh","doi":"10.1007/s00795-022-00346-5","DOIUrl":"https://doi.org/10.1007/s00795-022-00346-5","url":null,"abstract":"<p><p>This study aimed to demonstrate and compare the accuracy of tooth shade selection due to the remineralized enamel crystal with enamel matrix derivative (EMD) in vitro. Etched enamel slices were immersed in four types of mineralization buffers for 16 h. Sodium fluoride (NaF) was added to final concentrations of 1-100 ppm with the mineralization buffer that demonstrated the highest mineralization efficiency. EMD was added to the mineralization buffer containing NaF to see if it has any remineralization capacities. The remineralized enamel crystal was analyzed by SEM and XRD. The tooth shade was evaluated by CIE L*a*b*. The results showed that, without NaF, plate-like nanocrystals were formed on the enamel surface, but with NaF, needle-like nanocrystals were formed. By adding EMD, a layer of well-compacted hydroxyapatite crystals was successfully precipitated onto the natural enamel surface. No significant differences were observed in the L* value of the mineralization surface pre-etching and after mineralization buffer containing NaF and EMD. A new method has been developed to recover the color quality of enamel, as well as to mineralize the tooth enamel by constructing hydroxyapatite crystals with mineralization buffers containing NaF and EMD on the etched tooth surface.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9996477","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}
Kaori Yoshimura, Yuko Tamano, Hiep Nguyen Canh, Li Zihan, Dong Le Thanh, Yasunori Sato, Takeshi Terashima, Shinji Shimoda, Kenichi Harada
{"title":"A novel pathologic marker, indoleamine 2,3-dioxygenase 1, for the cholangiopathy of immune checkpoint inhibitors-induced immune mediated hepatotoxicity as adverse events and the prediction of additional ursodeoxycholic acid treatment.","authors":"Kaori Yoshimura, Yuko Tamano, Hiep Nguyen Canh, Li Zihan, Dong Le Thanh, Yasunori Sato, Takeshi Terashima, Shinji Shimoda, Kenichi Harada","doi":"10.1007/s00795-022-00344-7","DOIUrl":"https://doi.org/10.1007/s00795-022-00344-7","url":null,"abstract":"<p><p>Immune-related adverse events (irAE) has been clarified according the usage of immune checkpoint inhibitors(ICI). We primarily found indoleamine 2,3-dioxygenase 1(IDO-1) as a histologic biomarker for the cholangiopathy of primary biliary cholangitis(PBC). In this study, we evaluated the utility of IDO-1 in identifying ICI-induced immune-mediated hepatotoxicity(IMH). Immunostaining for IDO-1 using liver sections of PBC, ICI-induced IMH and controls, revealed that IDO-1 expression in bile ducts is mostly restricted in PBC and ICI-induced IMH. In ICI-induced IMH, IDO-1-positive bile ducts is found in 2/2 cases of cholangitis type and also positive/focal ducts in 11/15 cases of hepatitis type. Moreover, in 8/13 positive/focal cases, ursodeoxycholic acid as well as steroids were needed to improve liver dysfunction, but just one case (1/4) in IDO-1-negative cases. One IDO-1 positive case of hepatitis type did not receive additional UDCA, but biliary enzymes worsen. In vitro study using cultured human biliary epithelial cells revealed that IDO-1 induction was found with the stimulation of IFN-γ. In conclusion, the presence of IDO-1-positive cells is found in bile ducts in hepatitic type as well as sclerosing cholangitis of ICI-induced IMH. IDO-1 is surely a valuable pathologic marker for diagnosing ICI-induced IMH and also for predicting an additional need of UDCA in clinical practice.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9531930","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":"Vitamin D metabolism in cancer: potential feasibility of vitamin D metabolism blocking therapy.","authors":"Sakura Kamiya, Yuna Nakamori, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara, Makoto Osanai","doi":"10.1007/s00795-023-00348-x","DOIUrl":"https://doi.org/10.1007/s00795-023-00348-x","url":null,"abstract":"<p><p>In this review, we discuss the possibility of the vitamin D metabolizing enzyme CYP24A1 being a therapeutic target for various tumors including breast, colorectal and prostate tumors. Given the pleiotropic cellular activity of vitamin D, its deficiency impairs its physiological function in target cells and results in various pathologies including cancer. In addition, accumulated data have shown that elevated expression of CYP24A1 promotes carcinogenesis in various cancer subtypes by decreasing the bioavailability of vitamin D metabolites. Thus, we propose the potential feasibility of vitamin D metabolism-blocking therapy in various types of human malignancies that express constitutive CYP24A1.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9848701","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":"Anti-inflammatory and antifibrotic effects of CBP/β-catenin inhibitor for hepatocytes: small molecular inhibitor, OP-724 possibly improves liver function.","authors":"Hirofumi Ouchi, Yuki Mizutani, Kaori Yoshimura, Yasunori Sato, Kiminori Kimura, Yushi Haruyama, Kenichi Harada","doi":"10.1007/s00795-022-00343-8","DOIUrl":"https://doi.org/10.1007/s00795-022-00343-8","url":null,"abstract":"<p><p>Wnt/β-catenin signals are associated with several functions, including organ fibrosis. A synthetic small molecule, OP-724 (prodrug of C-82), an inhibitor of cyclic AMP response element-binding protein (CREB)-binding protein (CBP)/β-catenin, has demonstrated antifibrotic activity in mouse models of hepatic fibrosis. OP-724 is mediated by profibrotic and antifibrotic cells, such as hepatic stellate cells, macrophages, and neutrophils. In this study, the direct effects of C-82 on hepatocytes in hepatic inflammation were investigated. Immortalized human hepatocytes were pretreated with inflammatory cytokines. Moreover, the alteration of mRNA and protein expressions of cytokines and chemokines associated with hepatic inflammation and fibrosis, and of mitochondria-related molecules after C-82 treatment were analyzed in this study. The mRNA expression of several proinflammatory and profibrotic chemokines was upregulated by the stimulation of these inflammatory cytokines. In addition, this increase was prevented by C-82. In particular, the protein secretion of CCL2, CCL5, CXCL1, CXCL9, and CXCL10 was noticeably upregulated by TNFα and prevented by additional C-82. Moreover, C-82 increased the VEGF-A and FGF-2 proteins, categorized as anti-inflammatory and antifibrotic molecules, respectively. It also increased the expression of mitochondrial components and mitochondrial membrane potential. In conclusion, C-82 inhibits hepatocyte-mediated proinflammation and fibrogenesis. It also directly activates the mitochondrial function, thus improving liver dysfunction.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9831283","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":"An extremely rare case of nonfunctioning parathyroid carcinoma occurring in a parathyroid adenoma.","authors":"Tsunehisa Nomura, Takuya Moriya, Kazuya Miyoshi","doi":"10.1007/s00795-023-00350-3","DOIUrl":"https://doi.org/10.1007/s00795-023-00350-3","url":null,"abstract":"<p><p>A 53-year-old woman with a 4-month history of fatigue and somnolence was referred to her local doctor because of the worsening of her symptoms. Marked increases in her serum calcium (13.0 mg/dl) and intact-parathyroid hormone (175 pg/ml) were found, she was referred to our hospital. On physical examination, there was a palpable 3 cm mass in her right neck. Ultrasonography showed a 1.9 × 3.6 cm circumscribed hypoechoic lesion in the caudal right lobe of the thyroid gland. There was very mild 99mTc-sestamibi scintigraphic accumulation. Her preoperative diagnosis was primary hyperparathyroidism due to parathyroid carcinoma, and surgery was performed. The tumor weighed 6300 mg and did not invade the surrounding area. The pathology showed a mixture of small cells thought to be parathyroid adenomas and large, pleomorphic nuclei and fissionable carcinomas. Immunostaining showed that the adenoma portion was PTH-positive, chromogranin A-positive, p53-negative, PAX8-positive, PGP 9.5-negative with a Ki 67 labeling index (LI) of 2.2%. Whereas the carcinoma portion was PTH-negative, chromogranin A-negative, p53-positive, PAX8-positive, PGP 9.5-positive with a Ki67 LI of 39.6%, showing a nonfunctioning aspect and highly malignant. Postoperatively, the patient is alive without recurrence 9 years later without hypercalcemia or recurrence. A case of nonfunctioning parathyroid carcinoma in an extremely rare parathyroid adenoma is reported.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9471207","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":"Immunohistochemical analysis of the distribution of RANKL: a case of disseminated carcinomatosis of bone marrow as the first presentation of relapse in curatively resected colorectal cancer.","authors":"Yoshitaka Shimada, Yasushi Nagaba, Hiroyuki Okawa, Kaori Ehara, Shinya Okada, Masanori Naito, Hiroaki Yokomori","doi":"10.1007/s00795-022-00342-9","DOIUrl":"https://doi.org/10.1007/s00795-022-00342-9","url":null,"abstract":"<p><p>Poorly differentiated adenocarcinoma of colorectal carcinoma (CRC) is a rare condition with poor prognosis. In this report, we describe a case of a 69-year-old man who underwent laparoscopic low anterior resection after being diagnosed with stage IIIB CRC. At 10 months post-operation, he developed fever and loss of appetite. Laboratory examination revealed > 120.0 μg/dL fibrin degradation products and > 60.0 μg/dL D-dimer. Bone marrow (BM) examination showed malignant epithelioid infiltrate with CK20 and CDX2 expression, leading to diagnosis of disseminated carcinomatosis of BM, which is rare in CRC and indicative of widespread disease throughout the body. Furthermore, immunohistochemistry revealed high expression of receptor activator of nuclear factor κB ligand (RANKL) in tumor cells, including budding cells of CRC and BM tissues. Thus, RANKL expression, which is known to indicate metastatic behavior of cancer cells, may play a critical role in promoting osteoclast formation, which has been associated with the pathogenesis of BM lesions.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9476541","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}