Wu H, Fujioka Y, Sakaguchi S
… +2 more, Suzuki Y, Nakano T
Med Mol Morphol
· 2022 Mar · PMID 34825978
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SARS-CoV-2 is the cause of COVID-19. The three-dimensional morphology of viral particles existing and multiplying in infected cells has not been established by electron tomography, which is different from cryo-electron t...SARS-CoV-2 is the cause of COVID-19. The three-dimensional morphology of viral particles existing and multiplying in infected cells has not been established by electron tomography, which is different from cryo-electron tomography using frozen samples. In this study, we establish the morphological structure of SARS-CoV-2 particles by three-dimensional reconstruction of images obtained by electron tomography and transmission electron microscopy of biological samples embedded in epoxy resin. The characteristic roots of spike structures were found to be arranged at the surface of a virion covered with an envelope. A high-electron-density structure that appears to be a nucleocapsid was observed inside the envelope of the virion on three-dimensional images reconstructed by electron tomography. The SARS-CoV-2 particles that budded in the vacuoles in the cytoplasm were morphologically identical to those found outside the cells, suggesting that mature and infectious SARS-CoV-2 particles were already produced in the vacuoles. Here, we show the three-dimensional morphological structure of SARS-CoV-2 particles reconstructed by electron tomography. To control infection, inhibition of viral release from vacuoles would be a new target in the development of prophylactic agents against SARS-CoV-2.
Med Mol Morphol
· 2022 Mar · PMID 34796378
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Polycystic ovary syndrome (PCOS) is a common endocrinopathy related to female infertility. We investigated the function of the microRNA-98-3p (miR-98-3p)/Yin-Yang-1 (YY1) axis to the pathophysiological processes in PCOS...Polycystic ovary syndrome (PCOS) is a common endocrinopathy related to female infertility. We investigated the function of the microRNA-98-3p (miR-98-3p)/Yin-Yang-1 (YY1) axis to the pathophysiological processes in PCOS mice. A mouse model of PCOS was established using dehydroepiandrosterone (DHEA). Hematoxylin and eosin (HE) staining was used to assess morphologic changes of the ovaries. Hormonal serum levels were measured by ELISA. Estrogen synthesis in OGCs was measured using chemiluminescence immunoassay. The viability, cell cycle, and apoptosis of ovarian granulosa cells (OGCs) were assessed by CCK-8, flow cytometry, and western blot. Luciferase reporter assays were conducted to examine the binding of miR-98-3p to YY1. YY1 was upregulated, while miR-98-3p was downregulated both in the ovarian tissues of PCOS mice and OGCs separated from PCOS mice and patients. YY1 Knockdown promoted OGC proliferation and inhibited apoptosis as well as increased estrogen production in OGCs. YY1 was verified to be targeted by miR-98-3p. Additionally, YY1 overexpression prevented the effects of miR-98-3p overexpression on the proliferation and apoptosis of OGCs. Importantly, miR-98-3p attenuated ovarian injury in PCOS mice. MiR-98-3p targets and downregulates YY1 expression, thereby affecting the proliferation and apoptosis of OGCs in PCOS.
Shaoqing L, Ting Z, Hao L
… +3 more, He Z, Wang Y, Ming Z
Med Mol Morphol
· 2022 Mar · PMID 34773514
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Ischemic cardiomyopathy is a common but underestimated cause of heart failure. This study investigated the myocardial-protective effects of nicorandil on rats with ischemic cardiomyopathy. In the present study, ischemic...Ischemic cardiomyopathy is a common but underestimated cause of heart failure. This study investigated the myocardial-protective effects of nicorandil on rats with ischemic cardiomyopathy. In the present study, ischemic cardiomyopathy rats model were used to evaluate the effects of nicorandil. Cardiac ultrasonography was employed to examine the changes of heart structure and heart function. Electron microscopy was employed to observe the changes of pathological ultrastructure of the myocardium. Western blot and enzyme-linked immunosorbent assays were employed to detect protein levels and Mitochondrial Ca concentration. The heart color ultrasound and myocardial pathology of the rats in the nicorandil group were improved significantly, the mitochondrial Ca concentration was decreased, the expressions of MFN-1, OPA-1, and Bcl were increased, and the expressions of the mitochondrial mitotic proteins DRP-1, VDAC1, CytC, and Bax were decreased in ICM rats' heart treatment with nicorandil, compared with ICM rats. Nicorandil can reduce myocardial pathological damage in ICM rats, which may be caused by promoting the opening of mitochondrial ATP-sensitive potassium channel and inducing the changes of mitochondrial dynamics to induce the reduction of myocardial cell apoptosis.
Kimura M, Saito A, Onodera S
… +4 more, Nakamura T, Suematsu M, Shintani S, Azuma T
Med Mol Morphol
· 2022 Mar · PMID 34739612
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Fibroblast growth factor 8 (FGF8) is known to be a potent stimulator of canonical Wnt/β-catenin activity, an essential factor for tooth development. In this study, we analyzed the effects of co-administration of FGF8 and...Fibroblast growth factor 8 (FGF8) is known to be a potent stimulator of canonical Wnt/β-catenin activity, an essential factor for tooth development. In this study, we analyzed the effects of co-administration of FGF8 and a CHIR99021 (GSK3β inhibitor) on differentiation of dental mesenchymal cells into odontoblasts. Utilizing Cre-mediated EGFP reporter mice, dentin matrix protein 1 (Dmp1) expression was examined in mouse neonatal molar tooth germs. At birth, expression of Dmp1-EGFP was not found in mesenchymal cells but rather epithelial cells, after which Dmp1-positive cells gradually emerged in the mesenchymal area along with disappearance in the epithelial area. Primary cultured mesenchymal cells from neonatal tooth germ specimens showed loss of Dmp1-EGFP positive signals, whereas addition of Wnt3a or the CHIR99021 significantly regained Dmp1 positivity within approximately 2 weeks. Other odontoblast markers such as dentin sialophosphoprotein (Dspp) could not be clearly detected. Concurrent stimulation of primary cultured mesenchymal cells with the CHIR99021 and FGF8 resulted in significant upregulation of odonto/osteoblast proteins. Furthermore, increased expression levels of runt-related transcription factor 2 (Runx2), osterix, and osteocalcin were also observed. The present findings indicate that coordinated action of canonical Wnt/β-catenin and FGF8 signals is essential for odontoblast differentiation of tooth germs in mice.
Inoue H, Torigoe K, Torigoe M
… +8 more, Muta K, Obata Y, Suzuki T, Suzuki C, Abe T, Koji T, Mukae H, Nishino T
Med Mol Morphol
· 2022 Mar · PMID 34622315
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Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis, attributable to inflammation and mitochondrial dysfunction. Mitochonic acid-5 (MA-5), an indole-3-acetic acid derivative, improves mitochond...Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis, attributable to inflammation and mitochondrial dysfunction. Mitochonic acid-5 (MA-5), an indole-3-acetic acid derivative, improves mitochondrial dysfunction and has therapeutic potential against various diseases including kidney diseases. However, whether MA-5 is effective against peritoneal fibrosis remains unclear. Therefore, we investigated the effect of MA-5 using a peritoneal fibrosis mouse model. Peritoneal fibrosis was induced in C57BL/6 mice via intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 3 weeks. MA-5 was administered daily by oral gavage. The mice were divided into control, MA-5, CG, and CG + MA-5 groups. Following treatment, immunohistochemical analyses were performed. Fibrotic thickening of the parietal peritoneum induced by CG was substantially attenuated by MA-5. The number of α-smooth muscle actin-positive myofibroblasts, transforming growth factor β-positive cells, F4/80-positive macrophages, monocyte chemotactic protein 1-positive cells, and 4-hydroxy-2-nonenal-positive cells was considerably decreased. In addition, reduced ATP5a1-positive and uncoupling protein 2-positive cells in the CG group were notably increased by MA-5. MA-5 may ameliorate peritoneal fibrosis by suppressing macrophage infiltration and oxidative stress, thus restoring mitochondrial function. Overall, MA-5 has therapeutic potential against peritoneal fibrosis.
Chakraborti S, Paul RR, Pal M
… +2 more, Chatterjee J, Das RK
Med Mol Morphol
· 2022 Mar · PMID 34482436
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This paper focuses on the status of epithelial markers, E-cadherin, and p63 in the backdrop of an abnormal amount of collagen in the sub-mucosa of dysplastic and non-dysplastic grades of OSF. Histologically confirmed OSF...This paper focuses on the status of epithelial markers, E-cadherin, and p63 in the backdrop of an abnormal amount of collagen in the sub-mucosa of dysplastic and non-dysplastic grades of OSF. Histologically confirmed OSF and normal oral mucosa samples were procured. Samples were stained by Van Gieson's stain (VG) and immunohistochemistry. The captured images were analyzed by ImageJ software to quantify their grayscale intensities. There was a gradual increase in the intensity of VG stain from normal to non-dysplastic and dysplastic OSF and the differences in their mean grayscale values were found to be significant (p < 0.00001). The intensity of E-cadherin was found to be the highest in non-dysplastic conditions and lowest in dysplastic conditions. The intensity difference of E-cadherin between normal and non-dysplastic OSF was found to be significant (p < 0.00001). The grayscale scale intensity values for p63 in whole epithelium depicted significant differences between normal and diseased conditions but for its intensity, in basal cells, significant differences were found between non-dysplastic and other classes of tissues. There was a positive correlation observed between VG and p63 staining intensity. The diseased oral epithelium demonstrated greater deposition of sub-epithelial collagen fibers along with subsequent loss of E-cadherin and an increased p63 expression.
Nasu K, Aoyagi Y, Zhu R
… +4 more, Okamoto M, Yano M, Kai K, Kawano Y
Med Mol Morphol
· 2022 Mar · PMID 34463829
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Endometriosis is a common, estrogen-dependent benign tumor that affect 3-10% women of reproductive age, and is characterized by the ectopic growth of endometrial tissue, which is found primarily in the rectovaginal septu...Endometriosis is a common, estrogen-dependent benign tumor that affect 3-10% women of reproductive age, and is characterized by the ectopic growth of endometrial tissue, which is found primarily in the rectovaginal septum, ovaries, and pelvic peritoneum. To date, accumulating evidence suggests that various epigenetic aberrations, including the expression of aberrant microRNAs (miRNAs), play definite roles in the pathogenesis of endometriosis. This review summarizes the recent findings on the aberrantly repressed miRNAs, as well as their potential roles regarding the pathogenesis of endometriosis.
Chen TJ, Dehghanian SZ, Chan TC
… +6 more, He HL, Li WS, Abdollahi S, Chen NY, Li CF, Shiue YL
Med Mol Morphol
· 2021 Dec · PMID 34398348
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Data mining on a public domain detected eight potential transcripts which were upregulated in advanced UBUCs, suggesting that they may take part in UC development or/and progression. Retrospectively, immunohistochemistry...Data mining on a public domain detected eight potential transcripts which were upregulated in advanced UBUCs, suggesting that they may take part in UC development or/and progression. Retrospectively, immunohistochemistry along with H-score recording was carried out to evaluate the GNB4 protein levels on tissues from UC patients. Correlations between GNB4 H-score and imperative clinicopathological factors, as well as the implication of GNB4 protein level on disease-specific and metastasis-free survivals were assessed. In UTUCs (n = 340) and UBUCs (n = 295), 170 (50.0%) and 148 (50.0%) cases, respectively, were identified to be of high GNB4 expression. The GNB4 protein levels were correlated to numerous clinicopathological features and patients' survivals. Upregulation of the GNB4 protein was significantly associated with primary tumor, nodal metastasis, histological grade, vascular invasion and mitotic rate. High GNB4 protein levels independently and significantly predicted poor disease-specific and metastasis-free in UTUC and UBUC, respectively. Ingenuity pathway analysis furthermore showed that multiple signaling pathways were enriched including 'Communication between Innate and Adaptive Immune Cells' and 'NFκB Signaling'. Our findings demonstrated that the upregulation of the GNB4 protein is an independent unfavorable prognosticator in UC. High GNB4 gene expression plays an important role in UC progression.
Watanabe H, Fujishima F, Fukuhara N
… +3 more, Taniuchi S, Joh K, Sasano H
Med Mol Morphol
· 2022 Mar · PMID 34396490
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Myelofibrosis is characterized by stem cell-derived clonal proliferation potentially resulting in bone marrow fibrosis. As the disease progresses, extramedullary hematopoiesis is frequently detected in the spleen and the...Myelofibrosis is characterized by stem cell-derived clonal proliferation potentially resulting in bone marrow fibrosis. As the disease progresses, extramedullary hematopoiesis is frequently detected in the spleen and the liver but rarely in other organs. We report a case of a 68-year-old woman with myelofibrosis with a JAK2 mutation, showing extramedullary hematopoiesis (EMH) in various organs with a marked increase in reticulin fibers, and myeloproliferative neoplasm (MPN)-related necrotizing crescent glomerulonephritis. She was admitted to our hospital owing to respiratory discomfort. Computed tomography revealed a mass in the anterior mediastinum. Ten days later, the patient died owing to respiratory distress. At autopsy, EMH were detected in the anterior mediastinum, heart, lung, spleen, and the kidney with a marked increase in reticulin fibers. We considered that respiratory distress was partially caused by EMH. In the kidney, necrotizing crescent glomerulonephritis was observed. Immunohistochemically, the glomerular basement and mesangial area were IgA- and C3d-positive. Ultrastructural examination revealed the presence of dense deposits in the subendothelial space and the mesangial and paramesangial areas. Thus, we suspected that MPN-related necrotizing crescentic glomerulonephritis harbored a pathogenesis similar to that of IgA-dominant post-infectious glomerulonephritis or IgA nephropathy. This case report could widen the spectrum of MPN- or EMH-related lesions.
Harada H, Sato MP, Otsuki N
… +3 more, Kawamura M, Kurose A, Satou T
Med Mol Morphol
· 2022 Mar · PMID 34392428
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Ghost cell is one of several unique cellular morphologies associated with aberrant keratinization. We encountered a novel parotid tumor containing numerous ghost cells and herein describe its histological features and di...Ghost cell is one of several unique cellular morphologies associated with aberrant keratinization. We encountered a novel parotid tumor containing numerous ghost cells and herein describe its histological features and discuss diagnostic problems. The patient was a 90-year-old Japanese male, who complained of swelling of the left parotid area for four months. Positron emission tomography indicated no cervical lymph node metastasis or distant metastasis. The tumor was successfully resected with no signs of recurrence or metastasis for six months after surgery. Histologically, the tumor was mainly composed of squamous cells forming irregularly shaped nests with a mixture of pleomorphic giant or multinucleated cells and bland basaloid cell. Keratinized areas were occupied by a prominent ghost cell population. Immunohistochemically, CK5/6 and CK19 were widely positive as well as AE1/AE3, p40 and p63. Nuclear expression of β-catenin was also observed. The present case can be regarded as a particular form of squamous cell carcinoma and is believed to contain a large number of ghost cells resulting from an unclear mechanism. However, it seems difficult to consider such tumors as a clinicopathologically independent entity at present. Applying a term such as "salivary ghost cell carcinoma" would be premature.
Minowa E, Kurashige Y, Islam ST
… +8 more, Yoshida K, Sakakibara S, Okada Y, Fujita Y, Bolortsetseg D, Murai Y, Abiko Y, Saitoh M
Med Mol Morphol
· 2021 Dec · PMID 34324049
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The stratified squamous epithelium has a multilayer structure formed by the differentiation of the keratinized epithelium, which covers the skin and oral mucosa. The epithelium plays a central role in regulating the inte...The stratified squamous epithelium has a multilayer structure formed by the differentiation of the keratinized epithelium, which covers the skin and oral mucosa. The epithelium plays a central role in regulating the interactions between the immune system and pathogens. The tight junction (TJ) barrier, which is composed of adhesion molecules called claudins (CLDN), is critical for the homeostasis of the skin and oral mucosa. Furthermore, the crucial roles of vitamin D3 (VD3) in the pathogeneses of skin and oral mucosal disease have been suggested. The aim of this in vitro study was to observe the correlations between the integrity of the keratinocyte population and the expression levels of CLDN1 and CLDN4 in gingival epithelial cells, stimulated with VD3. CLDN 1 and 4 expression levels were down and upregulated, respectively, in the cells stimulated with VD3. Additionally, transepithelial electrical resistance (TEER) levels were increased in the stimulated cells when compared to the controls. These findings indicate that CLDN 4 may play a more important role in the TJ barrier than CLDN 1. Hence, the therapeutic effect of VD3 in skin and oral diseases may be regulated by the increase in the expression of CLDN 4.
Mariya T, Sato T, Fujibe Y
… +11 more, Ishido M, Shimada H, Kubo T, Nagai Y, Arai W, Tanaka SE, Ashikawa K, Sakuraba Y, Ishioka S, Yokota SI, Saito T
Med Mol Morphol
· 2021 Dec · PMID 34287707
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Intrauterine infection is one of the most important causes of maternal death. In perinatal emergency, we often miss an opportunity to obtain culture specimens. In this study, we tried to examine whether we investigated w...Intrauterine infection is one of the most important causes of maternal death. In perinatal emergency, we often miss an opportunity to obtain culture specimens. In this study, we tried to examine whether we investigated whether bacteria causing infection can be detected from a formalin-fixed paraffin-embedded (FFPE) placental specimen. We examined the placenta from a maternal invasive infection that resulted in infectious abortion at 18 weeks of gestation. The case was diagnosed by acute fever and abdominal pain, and the patient was cured after 3 weeks of intensive antimicrobial treatment. Four Streptococcus pyogenes strains were isolated from vaginal fluid and blood cultures of the patient. All of the strain types were emm1/ST28. We amplified the V1-V2 region of 16S rRNA from an FFPE placental specimen and sequencing was performed using a next-generation sequencer (NGS). Taxonomic analysis was then performed for sequenced data. We succeeded in detecting causative pathogens from the FFPE placenta: 69.1% of the predominantly identified bacteria were S. pyogenes and other small populations of bacteria were detected. Our results revealed the utility of NGS for 16S rRNA analysis of an FFPE placenta. This method may reveal previous perinatal invasive infections of unknown origin retrospectively.
Med Mol Morphol
· 2021 Dec · PMID 34255190
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The purpose of this study is to explore whether LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-β1/Smad signaling pathway, influencing the abnormal proliferation of fibroblasts and excessive deposition of ECM...The purpose of this study is to explore whether LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-β1/Smad signaling pathway, influencing the abnormal proliferation of fibroblasts and excessive deposition of ECM in hypertrophic scar formation. PICSAR and miR-485-5p expressions were detected by qPCR. Cell proliferation was examined by CCK-8. Protein expressions were determined by western blot. Immunofluorescence detected the Ki-67 expression. Dual-luciferase followed by immunoprecipitation was performed to verify the interaction between PICSAR and miR-485-5p. Interference with PICSAR inhibited the abnormal proliferation of hypertrophic scar fibroblasts (HSFs) and the excessive deposition of ECM. It was also confirmed in our study that MiR-485-5p is a direct target of PICSAR in HSFs. Additionally, inhibition of miR-485-5p reversed the effect of PICSAR knockdown in HSFs. LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-β1/Smad signaling pathway, promoting the abnormal proliferation of fibroblasts and excessive deposition of ECM in hypertrophic scar formation.
Watanabe H, Ide R, Yamazaki Y
… +7 more, Fujishima F, Kasajima A, Yazdani S, Tachibana T, Motoi F, Unno M, Sasano H
Med Mol Morphol
· 2021 Dec · PMID 34247274
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Immunohistochemical analysis of somatostatin receptor 2 (SSTR2) provides important information regarding the potential therapeutic efficacy of somatostatin analogues (SSAs) in patients with neuroendocrine tumors. HER2 sc...Immunohistochemical analysis of somatostatin receptor 2 (SSTR2) provides important information regarding the potential therapeutic efficacy of somatostatin analogues (SSAs) in patients with neuroendocrine tumors. HER2 scoring has been proposed to interpret SSTR2 immunoreactivity but their reproducibility was relatively low because of its intrinsic subjective nature. Digital image analysis (DIA) has recently been proposed as an objective and more precise method of evaluating immunoreactivity. Therefore, in this study, we used DIA for analyzing SSTR2 immunoreactivity in pancreatic neuroendocrine tumors (PanNETs) to obtain its H score and "(%) strong positive cells" and compared the results with those of manually obtained HER2 scores. Membranous SSTR2 immunoreactivity evaluated by DIA was calculated by two scales as: "Membrane Optical Density" and "Minimum Membrane Completeness". PanNETs with HER2 score of > 2 demonstrated the highest concordance with results of "(%) strong positive cells" obtained by DIA when "Minimum Membrane Completeness" was tentatively set at 80%. The SSTR2 immunoreactivity, evaluated based on all scoring systems, was different between grades G1 and G2 in insulinoma but not in non-functional PanNETs. DIA provided reproducible results of SSTR2 immunoreactivity in PanNETs and yielded important information as to the potential application of SSAs.
Hashimoto M, Fujishima F, Lomphithak T
… +3 more, Jitkaew S, Nio M, Sasano H
Med Mol Morphol
· 2021 Dec · PMID 34159444
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Biliary atresia (BA) is characterized by the occlusion of extrahepatic bile ducts due to sclerosing inflammation. Necroptosis is a recently characterized form of programmed cell death but has not been examined in BA. We,...Biliary atresia (BA) is characterized by the occlusion of extrahepatic bile ducts due to sclerosing inflammation. Necroptosis is a recently characterized form of programmed cell death but has not been examined in BA. We, therefore, explored the potential involvement of necroptosis in the pathogenesis of BA by evaluating the correlation between necroptosis-related factors and clinicopathological features of BA patients. We studied liver biopsy specimens of 59 patients with BA and 30 with congenital biliary dilatation (CBD). We also evaluated 14 surgical BA cases, who eventually underwent liver transplantation and 9 normal liver from neonates and infants obtained at autopsy. Necroptosis-related factors including toll-like receptor 3 (TLR3), receptor-interacting protein kinase1 (RIP1), receptor-interacting protein kinase3 (RIP3), mixed lineage kinase domain-like (MLKL), and phosphorylated mixed lineage kinase domain-like (pMLKL) in these liver specimens were immunolocalized. TLR3, RIP1, MLKL in the intrahepatic cholangiocytes was significantly higher in BA than CBD. pMLKL immunoreactivity was significantly greater at an earlier age of BA patients. The native liver survival period was significantly prolonged in the high RIP3 group. The low RIP3 status could serve as an adverse clinical prognostic factor for the native liver survival among the necroptosis-related factors examined in this study.
Anami T, Komohara Y, Miura Y
… +10 more, Yamanaka K, Kurahashi R, Segawa T, Motoshima T, Murakami Y, Yatsuda J, Yamaguchi T, Sugiyama Y, Jinnouchi Y, Kamba T
Med Mol Morphol
· 2021 Dec · PMID 34136945
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Targeting the programmed cell death-1 signaling pathway has been approved for the anti-cancer therapy in several cancers including urothelial cancer. To determine predictive factors of the responsiveness to pembrolizumab...Targeting the programmed cell death-1 signaling pathway has been approved for the anti-cancer therapy in several cancers including urothelial cancer. To determine predictive factors of the responsiveness to pembrolizumab in urothelial cancer patients, a retrospective study that used clinical information and paraffin-embedded samples obtained from patients diagnosed with urothelial cancer between 2015 and 2020 were performed. Seventeen patients who underwent total cystectomy or nephroureterectomy of the primary lesion and were treated with pembrolizumab for chemo-resistant disease were enrolled, and immunohistochemical analysis was performed. A key difference in the characteristics between the non-responder group and the responder group was the age of the patients (74 vs. 63 years, p = 0.0194). Although there was no statistically significant difference, the histological subtype with sarcomatoid and micropapillary components was only seen in the non-responder group, and squamous differentiation and lymph node metastasis were only seen in cases with a complete response. In the results of immunohistochemistry, the density of CD8-positive T-cells and Tregs was significantly increased in the responder group than in the non-responder group. In conclusion, younger age and a high number of tumor-infiltrating lymphocytes were predictive factors of a good response to immune checkpoint inhibitors, although further studies with more enrolled patients are necessary.
Harada H, Matsumoto H, Nakatsuka SI
… +1 more, Kurose A
Med Mol Morphol
· 2021 Dec · PMID 34091759
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Lymphoepithelial carcinoma (LEC) shows characteristic histology of nesting growth of tumor cells with unclear differentiation against the lymphoid stroma background. Although rare in salivary glands, it has previously be...Lymphoepithelial carcinoma (LEC) shows characteristic histology of nesting growth of tumor cells with unclear differentiation against the lymphoid stroma background. Although rare in salivary glands, it has previously been recognized as a type of undifferentiated carcinoma but is currently clearly defined as an independent disease separate from undifferentiated carcinoma. We report a case of LEC that developed in the parotid gland and was immunohistochemically positive for p16, which suggested the causative involvement of human papillomavirus (HPV). The patient was a 38-year-old Japanese male aware of mass formation in the left parotid area for 8 years. Parotidectomy was performed and there have been no signs of recurrence or metastasis for 18 month post-operation. The tumor was histologically typical except for Epstein-Barr virus (EBV)-encoded small RNA (EBER)-negative in situ hybridization (ISH), but p16-positivity by immunohistochemistry, and also frequent contact with extended and expanded pre-existing ductal structures. Although usually strongly associated with EBV infection, the tumor could be regarded to have eventually reached completion as a LEC lesion associated with HPV infection possibly through the pathway shared with squamous cell carcinoma. EBER-ISH remains the most promising index for confirming diagnosis of LEC, but EBV-negative result alone should not prevent diagnosis of LEC.
Restrictive cardiomyopathy (RCM) is a rare primary myocardial disease, and its pathological features are yet to be determined. Restrictive cardiomyopathy with MHY7 mutation was diagnosed in a 65-year-old Japanese woman....Restrictive cardiomyopathy (RCM) is a rare primary myocardial disease, and its pathological features are yet to be determined. Restrictive cardiomyopathy with MHY7 mutation was diagnosed in a 65-year-old Japanese woman. Electron microscopy of a myocardial biopsy revealed electron-dense materials resulting from focal myocyte degeneration and necrosis as well as tubular structures and pseudo-inclusion bodies in some nuclei. These features may be associated with the pathogenesis of RCM.
Although intraductal carcinoma (IDC) of the salivary glands was previously called low-grade cribriform cystadenocarcinoma, it was newly categorized in the 4th version of the World Health Organization classification. We r...Although intraductal carcinoma (IDC) of the salivary glands was previously called low-grade cribriform cystadenocarcinoma, it was newly categorized in the 4th version of the World Health Organization classification. We report a case of IDC of the upper lip and examined it immunohistochemically and genetically. The patient was a 48-year-old Japanese female, who noticed a tiny nodule on her left upper lip. Histologically, the tumor cells, which had eosinophilic cytoplasm, exhibited papillary and solid growth patterns, and regions of suspected microinvasion or intraductal spread were also seen at the periphery of the tumor. Small necrotic foci were noted. Immunohistochemically, the tumor cells were diffusely positive for the androgen receptor, CK19, CK5/6, EGFR, and SOX10, whereas they were focally positive for GCDFP-15, S-100 protein, and mammaglobin. The tumor nests were surrounded by alpha-smooth muscle actin-p63-/calponin-/CK14-positive myoepithelial cells. The Ki-67 labeling index was 51.2%. Genetic analysis showed no evidence of the TRIM27-RET or NCOA4-RET fusion gene. We finally diagnosed the tumor as a high-grade mixed intercalated duct/apocrine-type IDC of the upper lip. IDC of the minor salivary glands is exceedingly rare. We discuss diagnostic problems associated with minor salivary gland lesions, and the "basal-like" phenotype of this case.
Randomization of left-right body asymmetry, situs viscerum inversus (heterotaxy), is commonly associated with primary ciliary dyskinesia (PCD) resulting from an abnormal ciliary structure, with approximately 50% of PCD p...Randomization of left-right body asymmetry, situs viscerum inversus (heterotaxy), is commonly associated with primary ciliary dyskinesia (PCD) resulting from an abnormal ciliary structure, with approximately 50% of PCD patients exhibiting organ laterality defects. I herein report an intrauterine fetal death case, in which an autopsy revealed two lobes of the bilateral lungs as well as heterotaxy of abdominal organs (right-sided spleen and inversion of the alimentary and biliary organs). Whole-exome sequencing (WES) identified a heterozygous single-nucleotide change (c.12775T>C) in exon 68 of the DNAH9 gene, which is a rare single-nucleotide polymorphism (SNP) of rs746081639 and results in the amino acid change of p.C4259R. WES also identified a rare SNP of rs763089682 (c.121G>A) in the RSPH1 gene that causes a heterozygous amino acid alteration of p.G41R. The frequencies of both SNPs, C in rs746081639 and A in rs763089682, are 0.00000824, and a polyphen-2 analysis predicted these amino acid changes to be probably damaging, with a score of 1.000. The combination of extremely rare SNPs in DNAH9 and RSPH1 genes might have been the possible mechanism underlying the development of the laterality defect in the present case.