Highly Metastatic Ovarian Yolk Sac Carcinoma in a Rat

We investigated a highly metastatic ovarian yolk sac carcinoma in a 52-week-old female Crl:CD(SD) rat. Macroscopically, the present case had severe ascites, bilateral ovarian masses and numerous nodules in the abdominal and thoracic cavities. Histopathologically, these masses and nodules were generally composed of two types of cells mimicking a parietal and visceral yolk sac. The parietal cells were round to polygonal, contained eosinophilic droplets and were arranged in nests and cords in the eosinophilic matrix. Both the intracytoplasmic droplets and the matrix were stained positively with PAS. The visceral cells were cylindriform, and proliferated in papillary and tubular patterns and occasionally formed Shiller-Duval body-like structures. In the dissemination sites, the neoplastic cells proliferated on the surface of the various tissues and often infiltrated into deeper parts of the tissues. Immunohistochemically, both neoplastic cells were positive for α-fetoprotein and keratin, and the eosinophilic matrix was positive for laminin. Ultrastructurally, the parietal cells had dilated rough endoplasmic reticulums, which were filled with electron-lucent laminated structures. The visceral cells had poorly to moderately developed intracytoplasmic organelles and were interconnected with desmosomes. Taken together, the present tumor was diagnosed as yolk sac carcinoma arising from the ovary and was characterized by not only high metastasis but also invasive infiltration with biphasic proliferation of the parietal and visceral cells

Exocyst complex component 2 is a potential host factor for SARS-CoV-2 infection

iPS細胞やオルガノイド技術を用いた新型コロナウイルス感染におけるEXOC2の機能解析. 京都大学プレスリリース. 2022-10-27.An important host factor in SARS-CoV-2 infection, identified using iPS cell and organoid technology. 京都大学プレスリリース. 2022-10-31.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an epidemic and spread rapidly all over the world. Because the analysis of host factors other than receptors and proteases has not been sufficiently performed, we attempted to identify and characterize host factors essential for SARS-CoV-2 infection using iPS cells and airway organoids (AO). Based on previous CRISPR screening and RNA-seq data, we found that exocyst complex component 2 (EXOC2) is one important host factor for SARS-CoV-2 infection. The intracellular SARS-CoV-2 nucleocapsid (N) expression level was decreased to 3.7 % and the virus copy number in cell culture medium was decreased to 1.6 % by EXOC2 knockdown. Consistently, immunostaining results showed that N protein-positive cells were significantly decreased by EXOC2 knockdown. We also found that EXOC2 knockdown downregulates SARS-CoV-2 infection by regulating IFNW1 expression. In conclusion, controlling the EXOC2 expression level may prevent SARS-CoV-2 infection and deserves further study

Dual inhibition of TMPRSS2 and Cathepsin B prevents SARS-CoV-2 infection in iPS cells

TMPRSS2とカテプシンBを標的とした新型コロナウイルスの感染阻害. 京都大学プレスリリース. 2021-10-21.A drug cocktail stops SARS-CoV-2 infection of stem cells. 京都大学プレスリリース. 2021-10-21.It has been reported that many receptors and proteases are required for SARS-CoV-2 infection. Although angiotensin-converting enzyme2 (ACE2) is the most important of these receptors, little is known about the contribution of other genes. In this study, we examined the roles of neuropilin-1, basigin, transmembrane serine proteases (TMPRSSs), and cathepsins (CTSs) in SARS-CoV-2 infection using the CRISPR interference system and ACE2-expressing human iPS cells. Double-knockdown of TMPRSS2 and CTSB reduced the viral load to 0.036±0.021%. Consistently, the combination of the CTPB inhibitor CA-074 methyl ester and the TMPRSS2 inhibitor Camostat reduced the viral load to 0.0078±0.0057%. This result was confirmed using four SARS-CoV-2 variants (B.1.3, B.1.1.7, B.1.351, and B.1.1.248). The simultaneous use of these two drugs reduced viral load to less than 0.01% in both female and male iPS cells. These findings suggest that compounds targeting TMPRSS2 and CTSB exhibit highly efficient antiviral effects independent of gender and SARS-CoV-2 variant

Successful Use of Pembrolizumab to Treat Refractory Thymic Carcinoma with High PD-L1 Expression

Thymic carcinoma is a relatively rare and aggressive thymic epithelial tumor. Herein, we report successful treatment of thymic carcinoma with pembrolizumab. A 68-year-old woman was admitted to our hospital for evaluation of chest pain. Chest computed tomography showed a mass in the anterior mediastinum and lymphadenopathy in the left cervical lymph node. Analysis of biopsy specimens detected squamous cell carcinoma in the left cervical lymph node, and immunohistochemical analysis showed 100% expression of programmed death-ligand 1 (PD-L1). Masaoka-Koga stage IVb thymic carcinoma was ultimately diagnosed. Since 3 cycles of first-line chemotherapy did not result in improvement, pembrolizumab was administered as second-line treatment every 3 weeks at a dosage of 200 mg. After 3 cycles of pembrolizumab treatment, the size of the anterior mediastinal tumor and metastatic lesions had notably decreased. Pembrolizumab may prove to be an effective therapy for thymic carcinoma with high PD-L1 expression

Molecular analysis of holocarboxylase synthetase deficiency: a missense mutation and a single base deletion are predominant in Japanese patients

AbstractHolocarboxylase synthetase (HCS) deficiency is an inherited disease of biotin metabolism characterized by a unique pattern of organic aciduria, metabolic acidosis, and skin lesions. By analysis of five patients in four unrelated families, two mutations were identified: a transition from T to C which causes an amino-acid substitution of proline for leucine at position 237 (L237P) and a single deletion of guanine (delG 1067) followed by premature termination. One patient was homozygous for the L237P mutation, three patients in two families were compound heterozygotes of the missense and deletion alleles, and the other patient was heterozygous for the L237P mutation. Inheritance was successfully demonstrated in all of the patients' families by a modified PCR followed by restriction enzyme digestion. The two mutations accounted for seven of eight mutant alleles, while neither mutation was detected in 108 normal healthy Japanese children (216 alleles). Transient expression in cultured fibroblasts from a patient showed that the L237P mutation was responsible for decreased HCS activity. These results suggest that the L237P and delG1067 mutations are frequent disease-causing mutations in Japanese patients with HCS deficiency. This PCR-based technique may therefore be useful for detecting mutations among Japanese patients

Promoting Effects of Sucrose-rich Diet on N-Nitrosobis (2-oxopropyl) amine-induced Pancreatic Carcinogenesis in Hamsters

It has been reported that there is an association between pancreatic cancer and obesity, impaired glucose metabolism and diabetes based on excess dietary fat and sugar intakes. A number of studies have suggested that a high-fat diet increases development of carcinomas in various organs and possible risk factors for pancreatic cancer. However, how an excess sugar intake promotes pancreatic carcinogenesis is still unknown. In the present study, we investigated the influence of an excess sugar intake on pancreatic carcinogenesis by administration of a sucrose-rich diet in which starch was replaced by sucrose in order to contain the same calories and other nutrients. Two similar experiments were performed. Six-week-old male Syrian golden hamsters were given N-nitrosobis (2-oxopropyl) amine (BOP) at a dose of 50 and 20 mg/kg body weight as a carcinogen in Week 0 and 1, respectively. In Week 2, the animals were divided into control and experimental groups. In experiment 1, 15 animals received a control diet or sucrose-rich diet in which 100% of the starch was replaced by sucrose, respectively. Since five animals fed on the sucrose-rich diet died by Week 12, the diet was changed to a sucrose-rich diet in which 50% of the starch was replaced by sucrose. In experiment 2, 15 animals received a control diet or sucrose-rich diet in which 50 or 20% of the starch was replaced by sucrose, respectively. All animals were sacrificed 25 weeks after the start of the experiment, and histological examination of the pancreas was performed. No significant difference was seen in the body weight at the end of the experiment. There were no significant differences in the glycosylated hemoglobin (HbA1c) and serum triglyceride, total cholesterol and HDL-cholesterol levels between the control and sucrose-rich diet groups in experiments 1 and 2. The incidence and number of carcinomas increased in hamsters fed the sucrose-rich diet compared with the control diet in experiments 1 and 2. These results suggest that an excess sucrose intake may promote the development of pancreatic cancer in hamsters

Via-switch FPGA with transistor-free programmability enabling energy-efficient near-memory parallel computation

We are developing field-programmable gate arrays (FPGAs) with a new non-volatile switch called via-switch. In via-switch FPGAs (VS-FPGAs), the via-switches required for reconfiguration are placed in the routing layer so that the entire transistor layer can be utilized for computing, and higher implementation density can be achieved compared to conventional SRAM FPGAs. Furthermore, since arithmetic units and memories for computing can be placed under the via-switch crossbar for routing, large-scale parallel operations can be realized where the memory and the arithmetic unit are adjacent to each other. These features enable operation with high energy efficiency. This article reports 65 nm prototype fabrication results and predicted the performance of the VS-FPGA designed for AI applications. We also present the developed application mapping flow and crossbar programming method. The VS-FPGA closes the gap between FPGA and application-specific integrated circuits (ASIC) with the performance advantage of the via-switch and via-switch copy scheme for FPGA-to-ASIC migration, contributing to the expansion of the FPGA usage

Immunohistochemical Detection of Propionibacterium acnes in Granulomas for Differentiating Sarcoidosis from Other Granulomatous Diseases Utilizing an Automated System with a Commercially Available PAB Antibody

Propionibacterium acnes is implicated in the pathogenesis of sarcoidosis. We investigated the usefulness of immunohistochemistry (IHC) with a commercially available P. acnes-specific monoclonal antibody (PAB antibody) for differentiating sarcoidosis from other granulomatous diseases. Formalin-fixed paraffin-embedded tissue samples from 94 sarcoidosis patients and 30 control patients with other granulomatous diseases were examined by the original manual IHC method. We also compared the detection frequency of P. acnes in sarcoid granulomas between manual and automated IHC methods. P. acnes was detected in sarcoid granulomas of samples obtained by transbronchial lung biopsy (64%), video-associated thoracic surgery (67%), endobronchial-ultrasound-guided transbronchial-needle aspiration (32%), lymph node biopsy (80%), and skin biopsy (80%) from sarcoidosis patients, but not in any non-sarcoid granulomas of the samples obtained from control patients. P. acnes outside granulomas, however, was frequently detected in both groups. The detection status of P. acnes in granulomas did not correlate with the clinical characteristics of sarcoidosis patients. The automated Leica system exhibited the best detection sensitivity (72%) and almost an identical localization for P. acnes in sarcoid granulomas compared with the manual method. IHC with a PAB antibody is useful for differentiating sarcoidosis from other granulomatous diseases by detecting P. acnes in granulomas. An automated method by the Leica system can be used in pathology laboratories for differential diagnosis of granulomas by IHC with the PAB antibody