Kamiya S, Nakamori Y, Takasawa A
… +5 more, Takasawa K, Kyuno D, Ono Y, Magara K, Osanai M
Med Mol Morphol
· 2023 Jun · PMID 36749415
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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 activ...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.
Ouchi H, Mizutani Y, Yoshimura K
… +4 more, Sato Y, Kimura K, Haruyama Y, Harada K
Med Mol Morphol
· 2023 Jun · PMID 36645521
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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 prot...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.
Sugaya H, Kurashige Y, Suzuki K
… +7 more, Sakakibara S, Fujita Y, Islam ST, Nezu T, Ito S, Abiko Y, Saitoh M
Med Mol Morphol
· 2023 Jun · PMID 36622467
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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...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.
Gunji M, Sawa C, Akiyama M
… +4 more, Mukai S, Takaki T, Kang D, Honda K
Med Mol Morphol
· 2023 Jun · PMID 36622466
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Gemcitabine (GEM) is an anticancer drug inhibiting DNA synthesis. Glomerular thrombotic microangiopathy (TMA) has been reported as an adverse effect. However, the precise mechanism of GEM-induced endothelial injury remai...Gemcitabine (GEM) is an anticancer drug inhibiting DNA synthesis. Glomerular thrombotic microangiopathy (TMA) has been reported as an adverse effect. However, the precise mechanism of GEM-induced endothelial injury remains unknown. Cultured human umbilical vein endothelial cells (HUVECs) in the confluent phase were exposed to GEM (5-100 μM) for 48 h and evaluated cell viability and morphology, lectin binding concerning sialic acid of endothelial glycocalyx (GCX), and immunofluorescent staining of platelet-endothelial cell adhesion molecule (PECAM) and vascular endothelial growth factor receptor 2 (VEGFR2). The mRNA expression of α2,6-sialyltransferase (ST6Gal1), sialidase (neuraminidase-1: NEU-1), and interleukin (IL)-1β and IL-6 was also evaluated. GEM exposure at 5 μM induced cellular shrinkage and intercellular dissociation, accompanied by slight attenuation of PECAM and VEGFR2 immunostaining, although cell viability was still preserved. At this concentration, lectin binding showed a reduction of terminal sialic acids in endothelial GCX, probably associated with reduced ST6Gal1 mRNA expression. IL-1β and IL-6 mRNA expression was significantly increased after GEM exposure. GEM reduced terminal sialic acids in endothelial GCX through mRNA suppression of ST6Gal1 and induced inflammatory cytokine production in HUVECs. This phenomenon could be associated with the mechanism of GEM-induced TMA.
Yoshimura K, Tamano Y, Nguyen Canh H
… +6 more, Zihan L, Le Thanh D, Sato Y, Terashima T, Shimoda S, Harada K
Med Mol Morphol
· 2023 Jun · PMID 36599971
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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 o...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.
Osanai M, Takasawa A, Takasawa K
… +3 more, Kyuno D, Ono Y, Magara K
Med Mol Morphol
· 2023 Mar · PMID 36592231
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Retinoic acid (RA) is an active metabolite of vitamin A, which is an essential signaling molecule involved in cell fate decisions, such as differentiation, proliferation, and apoptosis, in a wide variety of cell types. A...Retinoic acid (RA) is an active metabolite of vitamin A, which is an essential signaling molecule involved in cell fate decisions, such as differentiation, proliferation, and apoptosis, in a wide variety of cell types. Accumulated data have demonstrated that expression of RA-metabolizing enzymes, CYP26A1, B1, and C1 (cytochrome P450, family 26A1, B1, and C1, respectively), protects cells and tissues from exposure to RA through restriction of RA access to transcriptional machinery by converting RA to rapidly excreted derivatives. CYP26 enzymes play similar but separate roles in limiting the consequences of fluctuations in nutritional vitamin A. Recently, we found that RA depletion caused by expression of CYP26A1 promotes malignant behaviors of tumor cells derived from various tissues, implicating CYP26A1 as a candidate oncogene. We also showed that the expression levels of CYP26 enzymes are elevated in various types of cancer. We have provided evidence for oncogenic and cell survival properties of CYP26 enzymes, indicating that these molecules are possible therapeutic targets for CYP26-expressing malignancies.
Shimada Y, Nagaba Y, Okawa H
… +4 more, Ehara K, Okada S, Naito M, Yokomori H
Med Mol Morphol
· 2023 Jun · PMID 36478259
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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...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.
Torga T, Suutre S, Kisand K
… +2 more, Aunapuu M, Arend A
Med Mol Morphol
· 2023 Mar · PMID 36370214
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The aim of the study was to correlate the immunohistochemical expression of cartilage intermediate layer protein 2 (CILP-2) and discoidin domain receptor 2 (DDR2), and the ultrastructural changes in the cartilage with th...The aim of the study was to correlate the immunohistochemical expression of cartilage intermediate layer protein 2 (CILP-2) and discoidin domain receptor 2 (DDR2), and the ultrastructural changes in the cartilage with the degree of articular cartilage damage in osteoarthritis (OA) patients. Cartilage samples were obtained from twenty patients aged from 46 to 68 years undergoing total knee arthroplasty. In each patient, medial and lateral tibial plateau samples were analysed applying OARSI histopathology grading. Positive correlation was noted between the extent of CILP-2 staining intensity and OARSI grades. Abundant staining for CILP-2 was found in the superficial and middle layers and in the pericellular matrix (PCM) of the deep zone. Transmission electron microscopy studies demonstrated strong damage of chondrocytes, the organelles were often diminished or focally aggregated. As a characteristic finding, PCM was frequently expanded, which may reflect a pathogenic step in OA progression. In conclusion, CILP-2 may potentially be a relevant marker of OA progression as its expression correlated better with cartilage damage than the known marker of articular cartilage damage, DDR2.
Someya M, Hasegawa T, Tsuchiya T
… +13 more, Kitagawa M, Fukushima Y, Gocho T, Mafune S, Ikeuchi Y, Kozuka Y, Idogawa M, Hirohashi Y, Torigoe T, Iwasaki M, Matsuura M, Saito T, Sakata KI
Med Mol Morphol
· 2023 Mar · PMID 36367588
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Resistance of cervical cancer to radiotherapy with concurrent chemotherapy (CCRT) results in a poor prognosis. To identify new biomarkers for predicting the treatment response and prognosis, we explored exosomal microRNA...Resistance of cervical cancer to radiotherapy with concurrent chemotherapy (CCRT) results in a poor prognosis. To identify new biomarkers for predicting the treatment response and prognosis, we explored exosomal microRNA (miRNA) expression signatures associated with the outcome of cervical cancer patients treated with CCRT. Exosomes were isolated from the plasma of 45 patients prior to CCRT during 2014-2020, and miRNA analysis was performed by next-generation sequencing. At a median follow-up of 38 months, 26 patients were recurrence free, 15 patients had died of the disease, and 4 patients received salvage chemotherapy due to distant metastasis. Of the 2522 miRNAs detected, 9 (miR-148a-5p, 1915-3p, 3960, 183-5p, 196b-5p, 200c-3p, 182-5p, 374a-5p, and 431-5p) showed differential expression between the recurrence-free and recurrence groups. Patients were divided into high- and low-risk groups according to the cutoff of the miRNAs-based risk score calculated from respective expression levels. The high-risk group had significantly worse disease-specific survival than the low-risk group (p < 0.001). In addition, miR-374a-5p and miR-431-5p expression showed a weak inverse correlation with tumor-infiltrating CD8+ and FOXP3+ T cells, suggesting a potential inhibitory effect on CCRT by suppressing tumor immunity. This miRNA signature could improve non-invasive monitoring and personalized treatment for cervical cancer.
Kawano H, Kawamura K, Ishijima M
… +5 more, Abe K, Hayashi T, Eguchi M, Miura K, Maemura K
Med Mol Morphol
· 2023 Mar · PMID 36348099
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The etiology of peripartum cardiomyopathy (PPCM) is unknown. Therefore, we evaluated the etiology of patients clinically diagnosed with PPCM using endomyocardial biopsy. We studied five patients diagnosed with PPCM follo...The etiology of peripartum cardiomyopathy (PPCM) is unknown. Therefore, we evaluated the etiology of patients clinically diagnosed with PPCM using endomyocardial biopsy. We studied five patients diagnosed with PPCM following endomyocardial biopsy (age, 28-42 years; mean age, 35 years). Biopsied samples were evaluated using microscopy, including immunostaining and electron microscopy. The pathological findings were as follows: myocardial hypertrophy, myocardial fibrosis, and cell infiltration. Two patients were diagnosed with lymphocytic myocarditis, one with eosinophilic myocarditis, one with hypertensive heart disease, and one with a combination of hypertension and myocarditis. Endomyocardial biopsy suggested that the causes of PPCM were varied and related to myocarditis and myocardial overload due to hypertension.
Sugita S, Takenami T, Kido T
… +9 more, Aoyama T, Hosaka M, Segawa K, Sugawara T, Fujita H, Murahashi Y, Emori M, Tsuyuki A, Hasegawa T
Med Mol Morphol
· 2023 Mar · PMID 36344703
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Superficial CD34-positive fibroblastic tumor (SCPFT) is a fibroblastic/myofibroblastic soft tissue tumor of rarely metastasizing intermediate malignancy. Some recent studies have described a relationship between SCPFT an...Superficial CD34-positive fibroblastic tumor (SCPFT) is a fibroblastic/myofibroblastic soft tissue tumor of rarely metastasizing intermediate malignancy. Some recent studies have described a relationship between SCPFT and PRDM10-rearranged soft tissue tumor (PRT) based on SynCAM3 and PRDM10 expression on immunohistochemistry. We performed CD34, cytokeratin AE1/AE3, SynCAM3, and PRDM10 immunohistochemistry in SCPFT and its histological mimics, including myxoinflammatory fibroblastic sarcoma (MIFS), superficially localized myxofibrosarcoma (MFS), and undifferentiated pleomorphic sarcoma. We also examined cyclin D1 expression because it is expressed in MIFS and MFS. We conducted fluorescence in situ hybridization (FISH) of PRDM10 rearrangement in SCPFT cases. On immunohistochemistry, only SCPFT showed strong and diffuse SynCAM3 expression. SCPFT also exhibited strong nuclear and weak cytoplasmic cyclin D1 expression, which was similar to that observed in MIFS. Two of five SCPFT cases exhibited nuclear PRDM10 expression. FISH revealed PRDM10 split signals in 44% and 24% of tumor cells in two SCPFT cases showing nuclear PRDM10 expression on immunohistochemistry, respectively. A minority of non-SCPFT cases showed focal SynCAM3 expression, but a combination of SynCAM3 and cyclin D1 in addition to CD34 and cytokeratin AE1/AE3 may be useful for the differential diagnosis of SCPFT and its histological mimics.
Med Mol Morphol
· 2023 Mar · PMID 36219258
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A monoclonal antibody (mAb) was produced against a fluvoxamine (FLV)-bovine serum albumin conjugate that was specific to both the conjugate and free form of FLV. The mAb enabled us to develop an immunohistochemistry (IHC...A monoclonal antibody (mAb) was produced against a fluvoxamine (FLV)-bovine serum albumin conjugate that was specific to both the conjugate and free form of FLV. The mAb enabled us to develop an immunohistochemistry (IHC) method for pharmacokinetic analysis of FLV at the cell and tissue levels. We demonstrated that IHC can be used to detect the localization of FLV in the small intestine, kidney, and liver 1 h after drug administration at the cell and tissue levels. Protease digestion is an important factor for obtaining appropriate IHC staining results for localization of drugs. In this study, precise FLV localization could be determined with only 1 h of protease digestion in the kidneys, but in the small intestine and liver, the staining results with two digestive conditions had to be merged. IHC provided new findings, such as (1) nerve cells are likely to uptake more FLV than other cells and tissues; (2) the ability of reabsorption and secretion in the kidney varies depending on the site, and the amount of FLV in the primary urine is regulated downstream of the proximal tubule S3 segment; and (3) some of the FLV is excreted in the bile.
Kuriyama S, Yano M, Kusaba T
… +4 more, Zaitsu S, Nishida H, Yasuda M, Nasu K
Med Mol Morphol
· 2023 Mar · PMID 36183278
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Adenocarcinomas with clear cell morphology may be associated with elevated serum alpha-fetoprotein levels in various organs. We report the case of an alpha-fetoprotein-producing cervical adenocarcinoma with clear cell mo...Adenocarcinomas with clear cell morphology may be associated with elevated serum alpha-fetoprotein levels in various organs. We report the case of an alpha-fetoprotein-producing cervical adenocarcinoma with clear cell morphology and compare it immunohistochemically, molecularly, and virologically with cervical clear cell carcinoma, gastric-type mucinous carcinoma, and ovarian clear cell carcinoma. A 51-year-old Japanese woman was initially diagnosed with cervical clear cell carcinoma. The tumor was resistant to standard surgery, radiotherapy, and chemotherapy. Serum carcinoembryonic antigen and alpha-fetoprotein were elevated. The tumor was immunohistochemically positive for alpha-fetoprotein, human chorionic gonadotropin, cytokeratin 20, spalt-like transcription factor 4, glypican 3, MUC6, and HIK1083. Gene panel testing revealed CCNE1 amplification, CDKN2A loss, and TP53 R282W. We compared the present case with 120 ovarian clear cell carcinoma cases using a tissue microarray. Only one case (0.8%) showed very limited immunohistochemical positivity for alpha-fetoprotein. Of the 54 cases in which serum carcinoembryonic antigen was measured, only one (1.9%) was elevated (19.9 ng/mL). We diagnosed the case as alpha-fetoprotein-producing cervical gastric-type mucinous carcinoma with enteroblastic differentiation. In conclusion, alpha-fetoprotein-producing cervical adenocarcinoma is a rare but aggressive tumor. Clinicians and pathologists should be aware of this unfamiliar tumor, its diagnostic clues, prognostic markers, and treatment strategies.
Nakano D, Akiba J, Tsutsumi T
… +4 more, Kawaguchi M, Yoshida T, Koga H, Kawaguchi T
Med Mol Morphol
· 2022 Dec · PMID 36131166
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Sodium-glucose cotransporter 2 (SGLT2) occurs in the proximal renal tubule cells. We investigate the hepatic expression of SGLT2 and its related factors in patients with chronic liver disease. This is a retrospective hum...Sodium-glucose cotransporter 2 (SGLT2) occurs in the proximal renal tubule cells. We investigate the hepatic expression of SGLT2 and its related factors in patients with chronic liver disease. This is a retrospective human study. The liver tissues were biopsied from patients with chronic liver disease (n = 30). The expression levels of SGLT2 were evaluated by immunostaining. Furthermore, the undirected graphical model was used to identify factors associated with hepatic expression levels of SGLT2. The SGLT2 expression was observed in not only the kidney, but also the liver in immunostaining (SGLT2 intensity: kidney 165.8 ± 15.6, liver 114.4 ± 49.0 arbitrary units, P < 0.01) and immunoblotting. There was no significant difference in hepatic expression of SGLT2 in the stratified analysis according to age, sex, BMI, and the severity of the liver disease. In the undirected graphical model, SGLT2 directly interacted with various factors such as sex, fatty change, neutrophil-to-lymphocyte ratio, triglyceride, hemoglobin A1c, creatinine, and albumin (partial correlation coefficient 0.4-0.6 for sex and 0.2-0.4 for others). The expression of SGLT2 was observed in the hepatocytes of patients with chronic liver disease. The undirected graphical model demonstrated the complex interaction of hepatic expression levels of SGLT2 with gender, inflammation, renal function, and lipid/glucose/protein metabolisms.
Kanazawa Y, Takahashi T, Higuchi T
… +4 more, Miyachi R, Nagano M, Koinuma S, Shigeyoshi Y
Med Mol Morphol
· 2023 Mar · PMID 36107241
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The basement membrane (BM), mainly composed of collagen IV, plays an important role in the maintenance, protection, and recovery of muscle fibers. Collagen IV expression is maintained by the balance between synthetic and...The basement membrane (BM), mainly composed of collagen IV, plays an important role in the maintenance, protection, and recovery of muscle fibers. Collagen IV expression is maintained by the balance between synthetic and degradative factors, which changes depending on the level of muscle activity. For example, exercise increases collagen IV synthesis, whereas inactivity decreases collagen IV synthesis. However, the effects of stretching on the BM structure remain unclear. Therefore, to investigate the effects of stretching on the BM of the skeletal muscle, we continuously applied stretching to the rat soleus muscle and examined the altered expression of BM-related factors and structure using quantitative polymerase chain reaction (qPCR), western blotting, zymography, immunohistochemistry, and electron microscopy. The results show that stretching increased the matrix metalloproteinase 14 (MMP14) expression and MMP2 activity, and decreased the collagen IV expression and width of the lamina densa in the soleus muscle. These results suggest that stretching promotes BM degradation in the rat soleus muscle. The findings of this study indicate a new influence of stretching on skeletal muscles, and may contribute to the new use of stretching in rehabilitation and sports fields.
Hiramatsu N, Yamamoto N, Ohkuma M
… +4 more, Nagai N, Miyachi EI, Yamatsuta K, Imaizumi K
Med Mol Morphol
· 2022 Dec · PMID 35932315
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When regenerated tissue is generated from induced pluripotent stem cells (iPSCs), it is necessary to track and identify the transplanted cells. Fluorescently-labeled iPSCs synthesize a fluorescent substance that is easil...When regenerated tissue is generated from induced pluripotent stem cells (iPSCs), it is necessary to track and identify the transplanted cells. Fluorescently-labeled iPSCs synthesize a fluorescent substance that is easily tracked. However, the expressed protein should not affect the original genome sequence or pluripotency. To solve this problem, we created a cell tool for basic research on iPSCs. Iris tissue-derived cells from GFP fluorescence-expressing mice (GFP-DBA/2 mice) were reprogrammed to generate GFP mouse iris-derived iPSCs (M-iris GFP iPSCs). M-iris GFP iPSCs expressed cell markers characteristic of iPSCs and showed pluripotency in differentiating into the three germ layers. In addition, when expressing GFP, the cells differentiated into functional recoverin- and calbindin-positive cells. Thus, this cell line will facilitate future studies on iPSCs.
Akimoto T, Takasawa A, Takasawa K
… +8 more, Aoyama T, Matsuura M, Tamate M, Iwasaki M, Habata S, Murakami T, Osanai M, Saito T
Med Mol Morphol
· 2022 Dec · PMID 35876908
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Desmoplastic reaction (DR) and inflammation are significant pathological manifestations of tumorigenesis in several cancers. However, the correlation between these stromal reactions and cervical adenocarcinoma has been p...Desmoplastic reaction (DR) and inflammation are significant pathological manifestations of tumorigenesis in several cancers. However, the correlation between these stromal reactions and cervical adenocarcinoma has been poorly documented. This investigation elucidated whether DR is a prognostic indicator in early cervical adenocarcinoma patients. Fifty-nine patients with early stage cervical adenocarcinoma (stages I/II) were included in the study. DR was divided into three groups, mature, intermediate, and immature, based on the presence of myxoid stroma and hyalinized keloid-like collagen. Inflammatory cell responses were classified as mild, moderate, and severe. Those stromal reactions were separately evaluated in the invasion front stroma and intratumoral stroma. In both the intratumor and invasion front stroma, intermediate/immature DR was correlated with tumor size, T stage, N stage, lymphovascular invasion, and parametrial infiltration (p < 0.001 to p < 0.05). In addition, in the intratumoral stroma, intermediate/immature DR led to short relapse-free survival and overall survival (p < 0.001). In the invasion front stroma, inflammatory cell responses were associated with DR immaturity and FIGO stage (p < 0.01). These results suggest that the classification of DR maturity is a potential prognostic biomarker in early stage cervical adenocarcinoma patients. DR can be evaluated by routine H&E staining without immunohistochemistry, making it convenient and economical in clinical practice.
Hata S, Shimada H, Sato N
… +7 more, Koshiishi M, Ise K, Ogata T, Yamashita S, Ito A, Sasano H, Nakamura Y
Med Mol Morphol
· 2022 Dec · PMID 35861941
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Glucocorticoid receptor (GR) has been implicated in prostate carcinoma growth and progression. Glucocorticoid receptor beta (GRβ) acts as an inhibitor of GR; however, its function is not well understood. Serum- and gluco...Glucocorticoid receptor (GR) has been implicated in prostate carcinoma growth and progression. Glucocorticoid receptor beta (GRβ) acts as an inhibitor of GR; however, its function is not well understood. Serum- and glucocorticoid-regulated kinase 1 (SGK1) is a GR-responsive gene that phosphorylates N-myc downstream-regulated gene 1 (NDRG1) and is involved in cancer growth and invasion. However, the expression of GR, GRβ, SGK1, and NDRG1 in prostate cancer and their relationship with clinicopathological and functional significance remain unknown. The association between the status of GR, GRβ, SGK1, and NDRG1 immunoreactivity and clinicopathological variables was analyzed in patients with prostate carcinoma to explore their clinical significance. In prostate carcinoma cases, the relative abundance of GR and NDRG1 immunoreactivity was inversely and significantly associated with the primary tumor stage (pT), while GR immunoreactivity was inversely and significantly associated with the Ki-67 score. The relative expression status of NDRG1 was significantly associated with that of GR. However, no significant correlation was observed between any of the clinicopathological parameters and GRβ and SGK1 expression. Our findings indicate that GR and NDRG1 expression status is correlated with clinicopathological features in patients with prostate cancer.
Med Mol Morphol
· 2023 Mar · PMID 35851413
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Juvenile polyposis syndrome (JPS) is a rare autosomal dominant inherited disease characterised by multiple juvenile polyps. Genes with JPS-associated mutations and their correlation with the phenotype are currently unkno...Juvenile polyposis syndrome (JPS) is a rare autosomal dominant inherited disease characterised by multiple juvenile polyps. Genes with JPS-associated mutations and their correlation with the phenotype are currently unknown. Gastrointestinal endoscopy results of a 31-year-old female patient showed multiple polyps in the digestive tract, and the presence of juvenile polyps was confirmed by pathological examination. During follow-up, the patient underwent total gastrectomy and polypectomy several times. Five members of this family were diagnosed with JPS, of which two died and three survived. Full exon gene sequencing of eight members of this family revealed a SMAD4 (NM-005359.3) c.1035C > A (p.Cys345*) mutation. This mutation leads to premature codon termination, causing protein truncation. SMAD4 is a pathogenic gene associated with JPS. This is the first report of an association between the c.1035C > A mutation and JPS pathogenesis. Detection of JPS-related mutations in family members with a genetic predisposition for JPS is very important for genetic counselling, surgical intervention, long-term monitoring and follow-up, and drug treatment.
Fertilization triggers a process called maternal-to-zygotic transition, in which the oocyte undergoes oocyte-to-embryo transition, leading to massive intracellular remodeling toward early embryogenesis. This transition r...Fertilization triggers a process called maternal-to-zygotic transition, in which the oocyte undergoes oocyte-to-embryo transition, leading to massive intracellular remodeling toward early embryogenesis. This transition requires the degradation of oocyte-derived components; however, the significance and mechanism of degradation of cell surface components remain unknown. In this review, we focused on the dynamics of plasma membrane proteins and investigated the relationship between embryonic development and endocytosis. Our survey of the extant literature on the topic led to the conclusion that clathrin-mediated endocytosis is essential for the progression of early embryogenesis and selective degradation of oocyte-derived plasma membrane proteins in mouse embryos, as reported by studies analyzing maternal cellular surface proteins, including a glycine transporter, GlyT1a. Evaluation of such endocytic activity in individual embryos may allow the selection of embryos with higher viability in assisted reproductive technologies, and it is important to select viable embryos to increase the rates of successful pregnancy and live birth. Although the early embryonic developmental abnormalities are mainly accompanied with chromosomal aneuploidy, other causes and mechanisms remain unclear. This review summarizes molecular biological approaches to early embryonic developmental abnormalities and their future prospects.