Hong Wu, Yoshihiko Fujioka, Shoichi Sakaguchi, Youichi Suzuki, Takashi Nakano
{"title":"Morphological analysis for two types of viral particles in vacuoles of SARS-CoV-2-infected cells.","authors":"Hong Wu, Yoshihiko Fujioka, Shoichi Sakaguchi, Youichi Suzuki, Takashi Nakano","doi":"10.1007/s00795-024-00381-4","DOIUrl":"10.1007/s00795-024-00381-4","url":null,"abstract":"<p><p>In this study, we analyzed the morphological structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human cells. We identified the two types of viral particles present within the vacuoles of infected cells. Using transmission electron microscopy, we observed that SARS-CoV-2 particles exhibited both low- and high-electron-density structures, which was further confirmed through three-dimensional reconstruction using electron tomography. The budding of these particles was exclusively observed within these vacuoles. Intriguingly, viral particles with low-electron-density structures were confined to vacuoles, whereas those with high-electron-density structures were found in vacuoles and on the cell membrane surface of infected cells. Notably, high-electron-density particles found within vacuoles exhibited the same morphology as those outside the infected cells. This observation suggests that the two types of viral particles identified in this study had different maturation status. Our findings provide valuable insights into the molecular details of SARS-CoV-2 particles, contributing to our understanding of the virus.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"124-135"},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic and histological analysis intraplacental choriocarcinoma: a case report.","authors":"Natsuko Takano, Masashi Takamura, Yosuke Mizuno, Yumi Mizuno, Shunsuke Tamaru, Kohei Nakamura, Hiroaki Soma, Takeshi Kajihara","doi":"10.1007/s00795-024-00382-3","DOIUrl":"10.1007/s00795-024-00382-3","url":null,"abstract":"<p><p>We report on single case of intraplacental choriocarcinoma (IC) coexisting with feto-maternal hemorrhage from our hospital, a rare malignant tumor that occurs in the chorionic villous trophoblast. To investigate genetic and epigenetic changes to the carcinogenesis of IC, we employed cancer gene panel analysis and whole methylation analysis from a recent case of IC. By Short Tandem Repeats analysis, we confirmed that the tumor of present IC was derived from concurrent normal chorionic villous trophoblast cells. No mutation was found in 145 cancer-related genes. Meanwhile, amplification in MDM2 gene was observed. Furthermore, we observed deferentially methylated CpG sites between tumor and surrounding normal placenta in present IC case. These observations suggest that IC might be arisen as a result of aberrations of methylation rather than of DNA mutations. Further studies are needed to clarify association between aberrant methylation and choriocarcinogenesis.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"147-154"},"PeriodicalIF":1.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11128402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IL-32 production from lung adenocarcinoma cells is potentially involved in immunosuppressive microenvironment.","authors":"Shukang Zhao, Lianbo Li, Yoshihiro Komohara, Eri Matsubara, Yusuke Shinchi, Ahmad Adawy, Hiromu Yano, Cheng Pan, Yukio Fujiwara, Koei Ikeda, Shinya Suzu, Taizo Hibi, Makoto Suzuki","doi":"10.1007/s00795-023-00378-5","DOIUrl":"10.1007/s00795-023-00378-5","url":null,"abstract":"<p><p>Interleukin 32 (IL-32) is a proinflammatory cytokine secreted from several kinds of cancer cells. In the present study, we investigated the significance of IL-32 in lung adenocarcinoma by immunohistochemistry and bioinformatics analysis. IL-32 was positive in cancer cells of 21 cases (9.2%) of total 228 cases. Increased IL-32 gene expression was linked to worse clinical course in TCGA analysis, however, IL-32 expression in immunohistochemistry was not associated to clinical course in our cohort. It was also found that high IL-32 expression was seen in cases with increased lymphocyte infiltration. In vitro studies indicated that IFN-γ induced gene expression of IL-32 and PD1-ligands in lung adenocarcinoma cell lines. IL-32, especially IL-32β, also induced overexpression of PD1-ligands in human monocyte-derived macrophages. Additionally, Cancer-cell-derived IL-32 was elevated by stimulation with anticancer agents. In conclusion, IL-32 potentially induced by inflammatory conditions and anticancer therapy and contribute to immune escape of cancer cells via development the immunosuppressive microenvironment. IL-32 might be a target molecule for anti-cancer therapy.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"91-100"},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marya Obeidat, Wisam Algargaz, Marwa Barukba, Khaldon Bodoor, Issa Mohamad, Farid Barakat, Samir Al Bashir
{"title":"Clinical and molecular characteristics of Jordanian oropharyngeal cancer patients according to P16 expression: a retrospective study and a report of a novel biomarker.","authors":"Marya Obeidat, Wisam Algargaz, Marwa Barukba, Khaldon Bodoor, Issa Mohamad, Farid Barakat, Samir Al Bashir","doi":"10.1007/s00795-024-00383-2","DOIUrl":"10.1007/s00795-024-00383-2","url":null,"abstract":"<p><p>The purpose of this study was to assess the clinicopathological features of oropharyngeal cancer patients in Jordan based on their HPV status. Sixty-nine biopsies from two hospitals were included. Tissue microarrays were prepared from formalin-fixed paraffin-embedded (FFPE) specimens and stained with antibodies for CDKN2A/P16, EGFR, PI3K, PTEN, AKT, pS473AKT, PS2mTOR, and TIMAP. The cohort was divided according to P16 expression. Chi-square test and survival analyses were employed to evaluate the variations among the study variables and determine the prognostic factors, respectively. P16 expression was found in 55.1% of patients; however, there was no significant association between P16 expression and the patients' clinicopathological features. The Kaplan-Meier test revealed that smoking in P16-positive group and younger age (< 58 years) negatively impacted disease-free survival (DFS) (P = 0.04 and P = 0.003, respectively). Multivariate Cox regression test indicated that smoking, age, PI3K, and AKT were negative predictors of DFS (P = 0.021, P = 0.002, P = 0.021, and P = 0.009, respectively), while TIMAP was a positive predictor (P = 0.045). Elevated P16 expression is found in more than half of the patients' specimens. DFS is negatively affected by younger age and the combined effect of smoking and P16 overexpression. TIMAP is overexpressed in P16-positive oropharyngeal cancer, and it is a favorable predictor of DFS.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"136-146"},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Utility of human epidermal growth factor 2 heterogeneity as a prognostic factor in triple-negative breast cancer","authors":"Eriko Narusawa, Sasagu Kurozumi, Ayaka Katayama, Yukio Koibuchi, Akira Ogawa, Daisuke Takata, Shoko Tokuda, Sayaka Obayashi, Tetsunari Oyama, Jun Horiguchi, Ken Shirabe, Takaaki Fujii","doi":"10.1007/s00795-024-00386-z","DOIUrl":"https://doi.org/10.1007/s00795-024-00386-z","url":null,"abstract":"<p>In some cases of human epidermal growth factor 2 (HER2)-negative breast cancer, including triple-negative breast cancer, HER2 expression is sporadically and strongly upregulated, a condition known as <i>HER2</i> heterogeneity. We investigated the clinicopathological features of patients with <i>HER2</i> heterogeneity in triple-negative breast cancers treated with neoadjuvant chemotherapy. Thirty-nine patients with triple-negative breast cancer who had undergone preoperative chemotherapy participated in this study. To assess for <i>HER2</i> heterogeneity, we used dual in situ hybridization slides. We evaluated the association between <i>HER2</i> heterogeneity and clinicopathological factors such as rates of pathologic complete response (pCR) and of recurrence-free survival. Of the 39 patients, 15 (38.5%) had cancers with <i>HER2</i> heterogeneity. The pCR rates were 13.3% among patients with <i>HER2</i> heterogeneity and 20.8% among those with <i>HER2</i> nonheterogeneity, but the difference was not significant. The recurrence-free survival rate was significantly lower in patients with <i>HER2</i> heterogeneity than in those without (<i>P</i> = 0.025). <i>HER2</i> heterogeneity is a significant predictor of poor prognosis in patients with triple-negative breast cancer treated with neoadjuvant chemotherapy.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":"21 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140573293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alpha-fetoprotein producing endometrioid carcinoma arising in an adenomyoma of the uterus","authors":"Yuzo Oyama, Takahiro Kusaba, Kasumi Takao, Eri Obata, Mitsutake Yano, Kazuhiro Kawamura, Haruto Nishida, Tsutomu Daa","doi":"10.1007/s00795-024-00384-1","DOIUrl":"https://doi.org/10.1007/s00795-024-00384-1","url":null,"abstract":"<p>We report a case of alpha-fetoprotein-producing endometrioid carcinoma (AFP-EC) that originated within an adenomyoma of the uterine corpus. A 76-year-old Japanese woman was incidentally discovered to have a uterine tumor along with multiple lung nodules. Upon surgical removal of the uterus, it was revealed that the tumor was situated within the adenomyoma. The tumor exhibited microfollicular structures and solid growth patterns, with hyaline globules, clear cell glands, and primitive tumor cells. Immunohistochemical analysis indicated the presence of germ cell markers, including AFP, SALL4, and glypican3, leading to final diagnosis of AFP-EC. Histopathologically, AFP-ECs exhibit characteristics similar to those of AFP-producing neoplasms in other organs. Furthermore, a nomenclature issue arises when distinguishing AFP-ECs from yolk sac tumors of the endometrium in older patients due to their shared features. The concept of retrodifferentiation or neometaplasia suggests that “endometrioid carcinoma with yolk sac tumor differentiation” or “endometrioid carcinoma with a primitive phenotype” may serve as more fitting terms for the diverse spectrum of AFP-producing neoplasms in the endometrium. In conclusion, this case underscores the diagnostic challenges posed by AFP-ECs arising from adenomyomas and emphasizes the need for refining the nomenclature and classification of AFP-producing neoplasms within the endometrium.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":"55 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Overexpression of SerpinB9 in non-seminomatous germ cell tumors.","authors":"Toshiki Anami, Yuki Ibe, Lianbo Li, Yoshihiro Komohara, Hiroki Hirao, Mamoru Harada, Hiromu Yano, Yukio Fujiwara, Takanobu Motoshima, Junji Yatsuda, Taizo Hibi, Tomomi Kamba","doi":"10.1007/s00795-023-00374-9","DOIUrl":"10.1007/s00795-023-00374-9","url":null,"abstract":"<p><p>Serpinb9 is an inhibitor of granzyme B and is potentially involved in the immune escape of tumor cells. In the present study, bioinformatics analysis using open databases suggested that SerpinB9 is overexpressed in testicular embryonal carcinoma. Immunohistological analysis was performed on 28 cases of testicular germ cell tumors to investigate the relationship between SerpinB9 expression in testicular germ cell tumors and the tumor immune environment. SerpinB9 was significantly upregulated in the non-seminoma group and inversely correlated with the number of tumor-infiltrating CD8-positive cells. In addition, yolk sac tumors were characterized by the loss of human leukocyte antigen-class I expression. These findings suggest that SerpinB9 contributes to the immune escape of testicular germ cell tumors. Targeting therapy for SerpinB9 might therefore be useful in immunotherapy for testicular germ cell tumors resistant to immune checkpoint inhibitors.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"68-75"},"PeriodicalIF":1.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sungjoon Park, Jaehyuck Choi, Jung-Kook Song, Bogun Jang, Young Hee Maeng
{"title":"Subcellular expression pattern and clinical significance of CBX2 and CBX7 in breast cancer subtypes.","authors":"Sungjoon Park, Jaehyuck Choi, Jung-Kook Song, Bogun Jang, Young Hee Maeng","doi":"10.1007/s00795-023-00368-7","DOIUrl":"10.1007/s00795-023-00368-7","url":null,"abstract":"<p><p>Chromobox (CBX)2 and CBX7, members of CBX family protein, show diverse expression patterns and contrasting roles in certain cancers. We aimed to investigate the subcellular expression patterns and clinical significances of CBXs in breast cancer (BC) subtypes, which have heterogeneous clinical course and therapeutic responses. Among the subtypes, the triple-negative BC (TNBC) is a heterogeneous group that lacks specific markers. We categorized TNBC into quadruple-negative BC (QNBC) and TNBC, based on androgen receptor (AR) status, to make the groups more homogeneous. Immunohistochemistry for CBX proteins was performed on 323 primary invasive BC tissues and their clinical significances were analyzed. Cytoplasmic CBX2 (CBX2-c) was linked to adverse clinicopathological factors and TNBC and QNBC subtypes. In contrast, nuclear CBX7 (CBX7-n) was associated with favorable parameters and luminal A subtype. CBX2-c expression increased progressively from that in benign lesions to that in in situ carcinomas and invasive cancers, whereas CBX7-n and AR expressions showed sequential downregulation. AR was lower in metastatic tissues compared to matched primary cancer tissues. We speculate that the upregulation of CBX2-c and downregulation of CBX7-n could play a role in breast oncogenesis and an adverse clinical course, suggesting them as potential prognostic markers and therapeutic targets in invasive BCs.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"11-22"},"PeriodicalIF":1.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10014072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment to a patient with SLC40A1-HC successfully treated using red blood cell apheresis.","authors":"Yasuaki Tatsumi, Hisao Hayash, Koichi Kato","doi":"10.1007/s00795-023-00375-8","DOIUrl":"10.1007/s00795-023-00375-8","url":null,"abstract":"","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"82"},"PeriodicalIF":1.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ultrastructural changes of vascular smooth muscle cells and resistance to vasospasm treatment in femoral arteries of an arteriosclerotic rat model.","authors":"Yuki Matsuoka, Michika Fukui, Masakatsu Hihara, Toshihito Mitsui, Ryo Karakawa, Natsuko Kakudo","doi":"10.1007/s00795-023-00372-x","DOIUrl":"10.1007/s00795-023-00372-x","url":null,"abstract":"<p><p>The objective of this study was to establish an animal model of arteriosclerosis for assessing vasospasm and to investigate the relationship between arteriosclerosis and vasospasm. Twelve-week-old male Sprague-Dawley rats were fed a diet supplemented with adenine and vitamin D (adenine/vitD). Body weight, blood, and femoral artery histopathology were assessed at 2, 4, and 6 weeks. Change in the femoral artery was examined by transmission electron microscope (TEM). Vasospasm was induced by administering epinephrine extravascularly into the femoral artery and released by the treatment with lidocaine as a vasodilator. During this period, the extravascular diameter and blood flow were measured. The rats in the adenine/vitD group developed renal dysfunction, uremia, hyperphosphatemia, and elevated serum alkaline phosphatase. Histological and TEM analyses of the femoral arteries in the treated rats revealed the degeneration of elastic fibers and extensive calcification of the tunica media and intima. Vascular smooth muscles were degenerated and osteoblasts were developed, resulting in calcified arteriosclerosis. Vasospasm in arteriosclerotic arteries was detected; however, vasodilation as well as an increase in the blood flow was not observed. This study revealed the development of vasospasm in the femoral arteries of the arteriosclerotic rats and, a conventional vasodilator did not release the vasospasm.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"45-58"},"PeriodicalIF":1.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138295503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}