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J-GLOBAL

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BACKGROUND: Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity. CASE PRESENTATION: This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated. CONCLUSIONS: Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.

DOI： 10.1186/s12903-023-03586-8

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Language：Japanese   Publisher：中国・四国整形外科学会  

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Language：Japanese   Publisher：(一社)日本臨床検査医学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publishing type：Research paper (scientific journal)  

With the rapid expansion of genomic medicine, more citizens are compelled to think about genetics in their daily lives. This study aims to explore appropriate types of educational media and methods to enlighten activities for genetics and hereditary cancer. We presented an 18-min YouTube video on genetics and hereditary cancer to participants at a scientific event, Science Agora 2020, and administered a web questionnaire to investigate their opinions about when and how citizens should start learning about genetics and hereditary cancer. We recruited 133 participants who watched the video, and 26.3% (35/133) responded to the questionnaire. Most of them were evaluated to understand and appreciate the contents of the video. They identified websites, or videos as suitable learning media, irrespective of their sex, age, or profession. They highlighted upper elementary school or junior high school as appropriate educational stages to start learning about genetics and hereditary cancer to facilitate collecting their own genetic information by themselves. Our findings show that educational institutions should provide opportunities to learn about genetics and hereditary cancers, especially for upper elementary school and junior high school students, using learning media, such as videos, depending on their level or demand.

DOI： 10.1007/s12687-023-00663-x

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(株)北隆館  

近年の遺伝子解析技術の進歩に伴い,個人が自身のゲノムや遺伝情報を入手する機会は急速に増加している。そのため,医療従事者のみならず,市民もゲノム情報に対する正しい知識を持つことが急務である。筆者らは,医療従事者・学生・市民を対象に,遺伝リテラシーの向上を目的とした取り組みを行ってきた。本稿では,その取り組みの一部を紹介する。(著者抄録)

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Language：Japanese   Publisher：(株)癌と化学療法社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00296&link_issn=&doc_id=20230324430008&doc_link_id=%2Fab8gtkrc%2F2023%2F005003%2F009%2F0314-0320%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2023%2F005003%2F009%2F0314-0320%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)  

Adenosine-to-inosine RNA editing is a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family. It has been discovered recently as an epigenetic modification dysregulated in human cancers. However, the clinical significance of RNA editing in patients with liver metastasis from colorectal cancer (CRC) remains unclear. The current study aimed to systematically and comprehensively investigate the significance of adenosine deaminase acting on RNA 1 (ADAR1) expression status in 83 liver metastatic tissue samples collected from 36 patients with CRC. The ADAR1 expression level was significantly elevated in liver metastatic tissue samples obtained from patients with right-sided, synchronous, or RAS mutant-type CRC. ADAR1-high liver metastasis was significantly correlated with remnant liver recurrence after hepatic metastasectomy. A high ADAR1 expression was a predictive factor of remnant liver recurrence (area under the curve = 0.72). Results showed that the ADAR1 expression level could be a clinically relevant predictive indicator of remnant liver recurrence. Patients with liver metastases who have a high ADAR1 expression requires adjuvant chemotherapy after hepatic metastasectomy.

DOI： 10.1038/s41598-023-29397-z

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Language：English  

A hereditary breast and ovarian cancer (HBOC) pedigree was detected via liquid biopsy, and cancer prevention was initiated for the patient's daughter, after receiving a definitive result from BRCA genetic testing. A 48-yearold woman with ovarian cancer was administered precision medicine, which used cell-free DNA from plasma. The results revealed a pathogenic variant of BRCA1 as a presumed germline pathogenic mutation. We confirmed the germline pathological variant BRCA1 c.81-1G> A and suggested treatment with a PARP inhibitor. One of her three children had the variant, was diagnosed as an unaffected pathogenic variant carrier, and was advised to initiate surveillance.

DOI： 10.18926/AMO/63908

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Authorship：Lead author   Language：Japanese  

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DOI： 10.1016/j.amjmed.2022.02.042

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Homologous recombination (HR) is a vital process for repairing DNA double-strand breaks. Germline variants in the HR pathway, comprising at least 10 genes, such as BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK2, NBS1(NBN), PALB2, RAD51C, and RAD51D, lead to inherited susceptibility to specific types of cancers, including those of the breast, ovaries, prostate, and pancreas. The penetrance of germline pathogenic variants of each gene varies, whereas all their associated protein products are indispensable for maintaining a high-fidelity DNA repair system by HR. The present review summarizes the basic molecular mechanisms and components that collectively play a role in maintaining genomic integrity against DNA double-strand damage and their clinical implications on each type of hereditary tumor.

DOI： 10.3390/ijms23010348

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Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title><sec>
<title>Background</title>
<italic>RAD51D</italic> (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including <italic>BRCA</italic> impairment, there is no clear evidence of the relationship between <italic>RAD51D</italic> variants and the risk of sarcoma development.


</sec><sec>
<title>Case presentation</title>
A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of <italic>RAD51D</italic> c.904-2A &gt; T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the <italic>RAD51D</italic> splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of <italic>RAD51D</italic> with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3′-end of intron 9 of <italic>RAD51D</italic>. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered <italic>RAD51D</italic>, this case provided novel evidence for the relationship of a <italic>RAD51D</italic> splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of <italic>RAD51D</italic> c.904-2A &gt; T as a potential predisposing factor for malignant tumors, including leiomyosarcoma.


</sec><sec>
<title>Conclusions</title>
We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of <italic>RAD51D</italic> as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline <italic>RAD51D</italic> splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.


</sec>

DOI： 10.1186/s13053-021-00205-x

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Other Link： https://link.springer.com/article/10.1186/s13053-021-00205-x/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Immune-related adverse events (irAEs) commonly involve the gastrointestinal tract, endocrine glands, skin, and liver, and rarely the nervous system. The pathomechanism of irAEs in the nervous system is unclear, and so characterizing these severe toxic effects is a priority, even if irAEs are uncommon in the nervous system. Our patient presented subacute muscle weakness and dysesthesia with colitis as irAEs caused by pembrolizumab, one of the anti-programmed death-1 (PD-1) antibodies. Electromyography revealed abundant fibrillations and fasciculations of upper and lower extremities and severe reduction in motor unit potentials; however, antineutrophil cytoplasmic antibodies, rheumatoid factor, autoantibodies against Hu and Yo, and anti-ganglioside antibodies, such as GQ1b, were undetectable in the serum. Although he was treated with high-dose glucocorticoids, antibiotics, and a monoclonal anti-tumor necrosis factor alpha (TNFα) antibody, he developed colonic perforation. The total colorectal resection was performed, and the resected colon showed mucosal defect and perforation. He died of lung aspergillosis. Postmortem examination revealed CD8-positive lymphocyte infiltration around neurons of dorsal root ganglia. The sciatic nerve displayed the widening of myelin laminae and thinning of myelinated fibers but not a decrease in the density of myelinated nerve fibers. In the sural nerve, the density of myelinated fibers slightly decreased, and some fibers showed less densely myelinated laminae. Drug safety information, including previous randomized trials of anti-PD-1 and anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibodies, showed that patients treated with anti-PD-1 antibodies appeared to have more frequent and severe peripheral neuropathies compared to those in patients who received anti-CTLA-4 antibodies (1.59% vs. 0.69%; Fisher exact test, P < 0.001; three severe events vs. zero severe events). The present results and drug safety information suggest that the pathomechanism of irAEs caused by anti-PD-1 antibodies is different from that by anti-CTLA-4 antibodies. The neurological irAEs might be clues to solving the pathomechanism of irAEs.

DOI： 10.1111/neup.12729

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/neup.12729

Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Scientific Information, Inc.  

BACKGROUND Juvenile polyposis syndrome is an uncommon, autosomal-dominant hereditary disease that is distinguished by multiple polyps in the stomach or intestinal tract. It is associated with a high risk of malignancy. Pathogenic variants in SMAD4 or BMPR1A account for 40% of all cases. CASE REPORT A 49-year-old woman underwent esophagogastroduodenoscopy because of exacerbation of anemia. She had numerous erythematous polyps in most parts of her stomach. Based on biopsy findings, juvenile polyposis syndrome (JPS) was suspected morphologically, but there was no evidence of malignancy. Colonoscopy showed stemmed hyperplastic polyps and an adenoma; video capsule endoscopy revealed no lesions in the small intestine. After preoperative surveillance, laparoscopic total gastrectomy with D1 lymph node dissection was performed to prevent malignant transformation. The pathological diagnosis was juvenile polyp-like polyposis with adenocarcinoma. In addition, a germline pathogenic variant in the SMAD4 gene was detected with genetic testing. CONCLUSIONS JPS can be diagnosed with endoscopy and genetic testing. Further, appropriate surgical management may prevent cancer-related death in patients with this condition.

DOI： 10.12659/ajcr.932241

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Language：Japanese   Publisher：西日本泌尿器科学会  

症例は45歳,男性。X-1年9月に肉眼的血尿と右腰痛を主訴に当院を受診し,単純CTで右腎上極に長径5cm大の腫瘤を認めた。腹部造影CTでは動脈相で早期濃染,後期相でwashout patternを伴う内部不整な腫瘤を同部位に認めたが,明らかなリンパ節・他臓器転移を認めなかった。右腎癌cT1bN0M0 Stage Iと診断し,同年10月に腹腔鏡下右腎摘除術を施行した。病理所見は,腫瘍細胞は淡明細胞や好酸性細胞が乳頭状・管状の構造を取り,細胞質に好酸性の核小体および核周囲明庭を認めた。Fumarate hydratase(FH)免疫染色陰性でFH欠損腎細胞癌と診断した。術後2ヵ月で多発骨転移を認め,International Metastatic RCC Database Consortium(IMDC) intermediate riskと判断し,イピリムマブ・ニボルマブ併用療法を開始した。4コース施行後,CT上新規の転移巣や転移巣の増大を認めなかった。遺伝学的検査でFH遺伝子の病的バリアントを認め,腎細胞癌の家族歴と合わせ,遺伝性平滑筋腫症-腎細胞癌症候群(hereditary leiomyomatosis and renal cell carcinoma syndrome;HLRCC)関連腎細胞癌と診断した。現在ニボルマブ単剤投与を継続中で,骨転移増悪や新規遠隔転移は認めていない。(著者抄録)

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Language：Japanese   Publisher：(一社)日本内分泌学会  

J-GLOBAL

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File： 03山本英喜_日本臨床検査医学会誌：最終版.pdf

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：English   Publisher：日本癌学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Lynch syndrome (LS), which is known as a hereditary cancer syndrome, is distinguished by microsatellite instability, represented by the altered number of repetitive sequences in the coding and/or non-coding region. Immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has been recognized as an useful technique for screening of LS. Previous study has shown that the assessment of IHC, however, requires specific caution due to variable staining patterns even without germline mutations in MMR genes. CASE PRESENTATION: A 48-year-old man, who had been treated for anaplastic astrocytoma, was referred to our department for the precise examination of progressing anemia. Whole-body examination revealed two advanced carcinomas in descending colon and stomach. A hypo-vascular mass lesion was detected in liver as well. Pathological diagnosis (on surgical specimens) was poorly differentiated adenocarcinoma in descending colon, moderately differentiated tubular adenocarcinoma in stomach, and liver metastasis, which is possibly from colon. It was suspected that this case would be Turcot's syndrome-type-1 due to its specific family history having two cases of colon cancer within the second relatives. Pathogenic frameshift mutations in codon 618 of MLH1 gene was identified. Immunohistochemical analyses (IHC) demonstrated complete loss of MLH1 immuno-expression as well as of PMS2 except for those in brain tumor. Although frameshift mutation was not found in MSH6 gene, histological expression of MSH6 was patchy in primary colon carcinoma and was completely lost in the metastatic site in liver. MSH6 expression in gastric carcinoma, a coincidental cancer in this case, was intact. An abnormal (C)8 region was identified by the cloned PCR of colon and liver tumors but not from gastric cancer. Frameshift mutation in a (C)8 tract in exon 5 of the MSH6 gene was also detected in liver metastasis. CONCLUSION: This case supports a plausible mechanism, proposed by a previous literature, for the reduced expression of MSH6 in a somatic mutation manner, which might preferentially happen in colon cancer rather than in stomach carcinoma in MLH1/PMS2-deficient type of Turcot's syndrome type 1.

DOI： 10.1186/s12881-020-01079-x

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1186/s12957-018-1552-x

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Other Link： http://link.springer.com/article/10.1186/s12957-018-1552-x/fulltext.html

Publishing type：Research paper (scientific journal)   Publisher：Anticancer Research USA Inc.  

DOI： 10.21873/anticanres.13403

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Impact Journals LLC  

Background: The prognostic value and the best method of testing of topoisomerase II alpha (TOP2A) status have not been established in modern tailored therapy based on breast cancer subtype. Results: The frequencies of TOP2A overexpression and TOP2A amplified were 55.8% and 9.5%, respectively. TOP2A overexpression correlated strongly with nonluminal A subtype (χ2-test, p &lt
0.001). TOP2A overexpression was significantly associated with relapse-free survival in luminal B breast cancer (n = 316
log rank test, p &lt
0.001) but not in other breast cancer subtypes. Cox regression analysis showed that TOP2A overexpression is a significant prognostic factor in luminal B breast cancer (hazard ratio (HR) 4.00, 95% confidence interval (CI) 1.65-9.54, p = 0.002). TOP2A amplified was recognized in HER2 positive breast cancer (p &lt
0.001). In HER2 positive breast cancer, TOP2A amplified (HR 0.30, 95% CI 0.085-1.07, p = 0.063) appeared to be a better prognostic factor. Conclusion: In modern tailored therapy, TOP2A overexpression can be a poor prognostic factor in luminal B breast cancer. In contrast, TOP2A amplified could be a better prognostic factor in HER2 positive breast cancer. Materials and methods: Between May 2005 and April 2015, a total of 643 consecutive non-metastatic invasive breast cancers were evaluated for TOP2A amplified using fluorescence in situ hybridization analysis (FISH) and for TOP2A overexpression using the immunohistochemistry assay. FISH ratios of 2 or higher were designated as TOP2A amplified, and TOP2A staining &gt
10% was defined as TOP2A overexpression. The prognostic values of TOP2A amplified and TOP2A overexpression were retrospectively evaluated.

DOI： 10.18632/oncotarget.25468

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File： Yamamoto_H_etal_Autocrine VEGF isoforms_and_EC.pdf

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

CD24 is a heavily glycosylated cell surface protein that is expressed in putative stem cells and is overexpressed in various human malignancies, yet the significant roles of CD24 in gastric cancer development are still elusive. We investigated the involvement of CD24 in gastric cancer aggressiveness, which is attributed to its heterogeneity. Cultured gastric cancer cells showed diverse expression patterns in CD24, whereas other defined cell surface markers, such as CD44 and CD133, were homogenous. Purely sorted CD24-negative gastric cancer cells showed strong alteration into the CD24-positive cell type in an autochthonous manner, and reached to steady expression levels. Our clinicopathological study revealed that CD24 positivity was an independent prognostic factor in both intestinal and diffuse types of gastric cancer. CD24 expression was correlated with the advanced stages, invasiveness, and lymph node metastasis of gastric cancer. Silencing of CD24 in cultured cells significantly decreased cell migration and invasion. Hypoxic treatment upregulated CD24 expression, and simultaneously induced cell motility and invasion of gastric cancer cells. Hypoxic treatment-induced CD24 expression was significantly attenuated by knockdown of hypoxia-inducible transcription factors. These data suggest that CD24-negative cells are capable of gaining cell motility and invasiveness through the induction of CD24, which is mediated by hypoxia. CD24 would be an attractive marker to define not only the heterogeneity but also the aggressiveness of gastric cancer cells. The mechanisms by which hypoxia induces CD24 expression would also be a potential therapeutic target for gastric cancer.

File： Fujikuni_et_al-2014-Cancer_Science.pdf

DOI： 10.1111/cas.12522

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Although duodenal perforation is currently an infrequent complication of medical procedures, its incidence in the future predictably will increase as endoscopic treatment of duodenal neoplasms becomes more frequently used. In some cases, duodenal perforation is difficult to treat even surgically. We report here a novel technique called 'triple-tube-ostomy' for the treatment of iatrogenic duodenal perforation. Since November 2009, there have been three cases of iatrogenic perforation of the duodenum, due to various causes, which we have treated with our novel technique. The main principles of the technique are biliary diversion, decompression of the duodenum, and early enteral nutrition. All patients who underwent the triple-tube-ostomy procedure had good postoperative courses, with few complications. The novel surgical technique we describe in this report is safe, reliable, easy to learn and perform, and led to a good postoperative course in all cases where we performed it. Copyright © 2011 S. Karger AG.

DOI： 10.1159/000335742

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1186/1477-7819-8-40

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Other Link： http://link.springer.com/article/10.1186/1477-7819-8-40/fulltext.html

DOI： 10.1186/1752-1947-4-366

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Language：English   Publishing type：Research paper (scientific journal)  

In patients with stage IV gastric cancer, systemic chemotherapy is the key treatment. Combination chemotherapy (cis-diamminedichloride platinum plus S-1 and docetaxel plus S-1) results in long-term survival in clinical practice. In selected cases, additional (adjuvant) surgery may result in further long-term survival. This study aimed to evaluate the effcacy of adjuvant surgery following the response to chemotherapy for advanced gastric cancer. Based on response to chemotherapy, the indications for adjuvant surgery (surgery after the response to chemotherapy) are that resection is expected to be curative rather than palliative, provided that no other distant metastases occur. The study included 20 advanced gastric cancer patients who had undergone gastrectomies after the response to the combination chemotherapy of docetaxel and S-1, between September 2003 and December 2008 at Hiroshima University Hospital. At a median follow-up of 980 days, the median overall survival was 855 days. A 2- and 3-year survival was observed in 80 and 54.9% of patients, respectively, following macroscopic curative surgery. In the palliative group, the median overall survival was 510 days, but a 3-year survival was not observed. In the partial response group, the median overall survival was 865 days and a 3-year survival was observed in 37% of patients. One-year survival was not observed in the stable disease group. The patient survival in the partial response group was statistically more prolonged than in the stable disease group. The median overall survival in patients with liver metastasis was 865 days, while that in patients with peritoneal dissemination was 510 days. In conclusion, adjuvant surgery may be effective in gastric cancer patients diagnosed as stage IV by means of liver or distant lymph node metastasis, except in cases of peritoneal dissemination.

DOI： 10.3892/ol_00000130

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Wnt5a is a representative ligand that activates the beta-catenin-independent pathway in Wnt signaling. Although it has been reported that abnormal activation of the Wnt/beta-catenin-dependent pathway is often observed in human prostate cancer, the involvement of the b-catenin-independent pathway in this cancer is unclear. Abnormal expression of Wnt5a and beta-catenin was observed in 27 (28%) and 49 (50%) of 98 prostate cancer cases, respectively, by immunohistochemical analyses. Simultaneous expression of Wnt5a and b-catenin was observed in only five cases, suggesting their exclusive expression. The positive detection of Wnt5a was correlated with high Gleason scores and biochemical relapse of prostate cancer, but that of b-catenin was not. Knockdown and overexpression of Wnt5a in human prostate cancer cell lines reduced and stimulated, respectively, their invasion activities, and the invasion activity required Frizzled2 and Ror2 as Wnt receptors. Wnt5a activated Jun-N-terminal kinase through protein kinase D (PKD) and the inhibition of PKD suppressed Wnt5a-dependent cell migration and invasion. In addition, Wnt5a induced the expression of metalloproteinase-1 through the recruitment of JunD to its promoter region. These results suggest that Wnt5a promotes the aggressiveness of prostate cancer and that its expression is involved in relapse after prostatectomy. Oncogene (2010) 29, 2036-2046; doi: 10.1038/onc.2009.496; published online 18 January 2010

File： Wnt5a & PCa; Yamamoto H et al; Oncogene 2010 front.pdf

DOI： 10.1038/onc.2009.496

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Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000320458

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：W B SAUNDERS CO-ELSEVIER INC  

BACKGROUND & AIMS: Wnt5a expression stimulates in vitro migration and invasion of cultured gastric cancer cells by an unknown mechanism and is also correlated with aggressiveness of gastric tumors. The aim of this study was to show that Wnt5a is involved in metastasis of gastric cancer cells in vivo and to explore the molecular mechanism by which Wnt5a regulates migration and invasion. METHODS: In an experimental liver metastasis assay, Wnt5a-knockdown gastric cancer cells were injected into the spleens of nude mice. Microarray anatyses were used to compare expression patterns between mouse fibroblast L cells that stably express wild-type and a inurant form of Wnt5a to investigate Wnt5a-dependent gene expression. The expression of genes found to be regulated by Writ5a was investigated in cultured gastric cancer cells. Immunohistochemical analyses were performed to measure levels of Wnt-regulated gene products in 153 gastric cancer samples. RESULTS: Knockdown of Wnt5a in gastric cancer cells reduced the number of liver metastases that formed in nude mice. Microarray analyses indicated that Wnt5a activity induced expression of the gene encoding laminin gamma 2, a subunit of the epithelial basement membrane protein laminin-5. Wnt5a induced the expression of laminin gamma 2 through the activation of protein kinase C and c-Jun-N-terminal kinase. The invasive activity of gastric cancer cells depended on laminin gamma 2; Wnt5a expression levels correlated with those of laminin gamma 2 in diffuse-scattered type gastric tumor samples from patients. CONCLUSIONS: Wnt5a contributes to gastric cancer progression by increasing metastatic potential. Wnt5a up-regulates laminin gamma 2 to mediate gastric cancer cell aggressiveness.

File： Hideki Yamamoto; Wnt5a & GCa (Gastroenterology).pdf

DOI： 10.1053/j.gastro.2009.02.003

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CELL PRESS  

Wnt and Dickkopf (Dkk) regulate the stabilization of beta-catenin antagonistically in the Wnt signaling pathway; however, the molecular mechanism is not clear. In this study, we found that Wnt3a. acts in parallel to induce the caveolin-dependent internalization of low-density-lipoprotein receptor-related protein 6 (LRP6), as well as the phosphorylation of LRP6 and the recruitment of Axin to LRP6 on the cell surface membrane. The phosphorylation and internalization of LRP6 occurred independently of one another, and both were necessary for the accumulation of beta-catenin. In contrast, Dkk1, which inhibits Wnt3a-dependent stabilization of beta-catenin, induced the internalization of LRP6 with clathrin. Knockdown of clathrin suppressed the Dkk1-dependent inhibition of the Wnt3a response. Furthermore, Dkk1 reduced the distribution of LRP6 in the lipid raft fraction where caveolin is associated. These results indicate that Wnt3a and Dkk1 shunt LRP6 to distinct internalization pathways in order to activate and inhibit the beta-catenin signaling, respectively.

File： Dev Cell 2008; Wnt3a & Dkk1; Yamamoto H, Sakane H, Yamamoto H et al.pdf

DOI： 10.1016/j.devcel.2008.04.015

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Event date： 2022.12

Language：Japanese  

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Event date： 2022.10

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Event date： 2022.10

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Event date： 2022.9

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Event date： 2022.9

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Event date： 2022.9

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Event date： 2022.9

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Event date： 2022.9

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Event date： 2022.9

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Event date： 2022.6

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Event date： 2022.6

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Event date： 2022.6

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Event date： 2022.4

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Event date： 2022

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Event date： 2022

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Event date： 2022

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Event date： 2022

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Event date： 2022

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Event date： 2022

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Event date： 2022

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Event date： 2022

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Event date： 2022

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Event date： 2022

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Event date： 2021.11.11 - 2021.11.14

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Event date： 2021.10

Language：Japanese  

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Event date： 2021.10

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Event date： 2021.10

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Event date： 2021.7

Language：Japanese  

約20年前にCYP11B1/B2キメラ遺伝子を確認しグルココルチコイド反応性アルドステロン症(GRA)と診断された日本人1家系3例(発端者、母、妹)のうち、発端者が出産した5歳と3歳の男児に対し遺伝子検査を行った。その結果、男児2人ともキメラ遺伝子を検出しGRA保因者であることが明らかとなった。また、キメラ遺伝子の交叉部位について検討した結果、2児と発端者は同一のシークエンスで、交叉部位はエクソン3とイントロン5間であった。2児とも高血圧を認めないが低レニン・高アルドステロン症を伴っており、今後、成人期までの慎重な経過観察が必要である。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01160&link_issn=&doc_id=20210811280023&doc_link_id=10.1507%2Fendocrine.97.S.Update_71&url=https%3A%2F%2Fdoi.org%2F10.1507%2Fendocrine.97.S.Update_71&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Event date： 2021.4

Language：Japanese  

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Event date： 2021

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Event date： 2021

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Event date： 2021

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Event date： 2021

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Event date： 2021

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Event date： 2021

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Event date： 2021

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Event date： 2020.10

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Event date： 2020

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Event date： 2020

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Event date： 2020

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Event date： 2020

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Event date： 2020

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Event date： 2020

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Event date： 2020

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Event date： 2020

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Event date： 2019.10

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Event date： 2019.7

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Event date： 2019.2.15 - 2019.2.16

Language：English   Presentation type：Symposium, workshop panel (public)  

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Event date： 2019

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Event date： 2010

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Presentation type：Symposium, workshop panel (nominated)  

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