{"title":"SLC13A5 plays an essential role in the energy shift to oxidative phosphorylation in cisplatin-resistant mesothelioma stem cells.","authors":"Marie Kato-Shinomiya, Hirokazu Sugino, Lei Wang, Yusuke Saito, Jintao He, Zen-Ichi Tanei, Yoshitaka Oda, Satoshi Tanikawa, Mishie Tanino, Jian Ping Gong, Masumi Tsuda, Shinya Tanaka","doi":"10.1111/pin.70001","DOIUrl":"10.1111/pin.70001","url":null,"abstract":"<p><p>Mesothelioma is a highly aggressive tumor affecting an increasing number of patients worldwide. Owing to the poor clinical outcomes associated with current therapies, the development of novel therapies that target cancer stem cells (CSCs) is desirable. Here, we examined the applicability of our previously established hydrogel-based rapid CSC generation method to human mesothelioma cell lines and further analyzed the characteristics of the induced mesothelioma stem cell (MesoSC) -like cells. Human mesothelioma cell lines cultured on hydrogels presented increased expression of pan-stem cell markers and acquired spheroid formation and early tumorigenicity, suggesting that MesoSC-like cells are highly malignant. Microarray analysis demonstrated that the expression of SLC13A5, a citrate transporter involved in TCA cycle, was significantly induced in the resulting MesoSC-like cells. The overexpression of SLC13A5 resulted in a metabolic shift toward oxidative phosphorylation, increased phosphorylation of ERK and YAP, and increased SOX2 expression, leading to increased cisplatin resistance. scRNA-seq database analysis revealed that clinical mesothelioma samples contained a small number of SLC13A5-expressing cells. Our findings suggest that the hydrogel-based CSC generation method is also effective for human mesothelioma cells and that SLC13A5 may contribute to MesoSC survival. The new properties of MesoSCs revealed in this study may provide clues for establishing future treatments.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"151-165"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256055","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}
Dana Perez, Tong Wu, Ritu Bhalla, Zhiyan Fu, Barbara A Centeno, Masoumeh Ghayouri, Kun Jiang, Gregory Lauwers, Yukihiro Nakanishi
{"title":"Clinicopathological study of squamoid morules in nineteen conventional colorectal adenomas.","authors":"Dana Perez, Tong Wu, Ritu Bhalla, Zhiyan Fu, Barbara A Centeno, Masoumeh Ghayouri, Kun Jiang, Gregory Lauwers, Yukihiro Nakanishi","doi":"10.1111/pin.13516","DOIUrl":"10.1111/pin.13516","url":null,"abstract":"<p><p>Squamoid morules are an intriguing finding rarely seen in colorectal adenomas, mimicking foci of microinvasion or neuroendocrine differentiation. We identified nineteen colorectal adenomas with squamoid morules and collected clinicopathological data. A representative block was chosen for immunohistochemistry. The expression of p40, p63, CK5/6, beta-catenin, synaptophysin, chromogranin, and Ki-67 in squamoid morules were examined immunohistochemically. The nineteen patients comprised fifteen males (79%) and four females (21%) ranging in age from 45 to 85 years (average: 59.4 years old). Fourteen adenomas were tubulovillous adenomas (average: 3.4 cm, ranging 1.0 to 6.0 cm) and five were tubular adenomas (average: 2.6 cm, ranging 1.6 to 3.0 cm). All foci of squamoid morules showed beta-catenin nuclear positivity and CK5/6 expression. Squamoid morules were focally positive for p63 in four adenomas and focally positive for p40 in two adenomas. In two adenomas squamoid morules are focally positive for synaptophysin, and in one adenoma chromogranin was focally positive. In all nineteen adenomas squamoid morules were negative for Ki-67. Squamoid morules are characterized by strong male predominance, large adenoma size, beta-catenin nuclear positivity, CK5/6 expression, and no Ki-67 expression. Beta-catenin nuclear expression is helpful in distinguishing squamoid morules from foci of microinvasion and neuroendocrine differentiation.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"145-150"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080657","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":"Exploring experimental models of prostate cancer in chemoprevention: Oxidative stress as a key pathway to translational research.","authors":"Aya Naiki-Ito, Taku Naiki, Satoru Takahashi","doi":"10.1111/pin.13509","DOIUrl":"10.1111/pin.13509","url":null,"abstract":"<p><p>Prostate cancer (PCa) is the second most common cancer in men globally. Its growth is driven by oxidative stress associated with inflammation, aging, and environmental factors, including diet and lifestyle. These factors contribute to multiple stages of PCa progression, including progression to castration-resistant prostate cancer (CRPC). Therefore, oxidative stress represents an intriguing target for PCa chemoprevention and treatment. In vivo experimental models are crucial for understanding the mechanisms of PCa development, validating chemopreventive and therapeutic approaches, and translating preclinical results into clinical applications. We established a transgenic rat for adenocarcinoma of the prostate (TRAP) model, a transgenic rat that efficiently develops androgen-dependent adenocarcinoma, pathologically and biologically mimicking human PCa progression, to clarify the mechanisms of tumor progression, including the involvement of oxidative stress, and established a system for screening the chemopreventive effects of agents against PCa. Additionally, we derived a CRPC model from the TRAP model and developed a distant metastasis model, providing a comprehensive multistage rat model of prostate carcinogenesis. This review presents findings on the molecular mechanisms of PCa and the chemopreventive effects of natural compounds with antioxidant properties, such as polyphenols. We additionally described the potential for repositioning existing drugs with antiandrogenic activity for PCa chemoprevention.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"131-144"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979532","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}
Reiji Muto, Hiroaki Miyoshi, Toshihiko Murayama, Koji Makino, Koichi Ohshima
{"title":"A Case of Primary Cutaneous T-Follicular Helper Cell Lymphoma, Follicular-Type.","authors":"Reiji Muto, Hiroaki Miyoshi, Toshihiko Murayama, Koji Makino, Koichi Ohshima","doi":"10.1111/pin.70003","DOIUrl":"10.1111/pin.70003","url":null,"abstract":"<p><p>This is a case of primary cutaneous T-follicular helper cell lymphoma, follicular-type. A 99-year-old woman was detected with cutaneous mass located in left greater trochanter area and buttock, which was suspected to be malignant lymphoma. Computed tomography revealed few regional lymph node enlargement. Skin biopsy was performed for diagnosis. Pathologically, diffuse and dense proliferation of medium-sized atypical lymphocytes was observed proliferating with a vague nodular pattern. The immunohistochemical analysis presented that atypical lymphocytes composing vague nodular lesion were positive for CD3, CD4, PD-1, ICOS, BCL6, and CXCL13. Additionally, diffuse medium-sized B-cell proliferation was also observed. The monoclonality of T-cell receptor-gamma and IgVH was confirmed by polymerase chain reaction. Here we described a primary cutaneous case of FTCL. In the 5th edition of the WHO classification, TFH lymphoma is limited to lymph node and there is no consensus regarding the management of extranodal TFH lymphoma. Further accumulation of extranodal counterpart of the cases and clinicopathological examination of extranodal and nodal lesions is desired.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"166-170"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586629","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}
Ae Ri Ahn, Kyoung Min Kim, Ho Sung Park, Kyu Yun Jang, Woo Sung Moon, Myoung Ja Chung
{"title":"Pathological predictor of progressive pulmonary fibrosis.","authors":"Ae Ri Ahn, Kyoung Min Kim, Ho Sung Park, Kyu Yun Jang, Woo Sung Moon, Myoung Ja Chung","doi":"10.1111/pin.13511","DOIUrl":"10.1111/pin.13511","url":null,"abstract":"","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"171-173"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409849","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}
Shunsuke Koga, Wei Du, Robert M Brody, Kumarasen Cooper
{"title":"Impact of human papillomavirus (HPV) association on the prognosis of pyriform sinus carcinoma: A retrospective cohort study.","authors":"Shunsuke Koga, Wei Du, Robert M Brody, Kumarasen Cooper","doi":"10.1111/pin.13512","DOIUrl":"10.1111/pin.13512","url":null,"abstract":"","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"127-129"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984577","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}
Ikumi Kitazono, Miki Murakami, Aya Takeda, Hirotsugu Noguchi, Takashi Tasaki, Mari Kirishima, Michiyo Higashi, Kazuhiro Ueda, Akihide Tanimoto
{"title":"Pulmonary pleomorphic carcinoma: A rare case showing arterial carcinomatosis mimicking pulmonary artery intimal sarcoma.","authors":"Ikumi Kitazono, Miki Murakami, Aya Takeda, Hirotsugu Noguchi, Takashi Tasaki, Mari Kirishima, Michiyo Higashi, Kazuhiro Ueda, Akihide Tanimoto","doi":"10.1111/pin.13508","DOIUrl":"10.1111/pin.13508","url":null,"abstract":"<p><p>A male in his seventies presented with lung cancer in the right lower lobe. The surgically resected specimen revealed a pleomorphic carcinoma featuring an adenocarcinoma component with lepidic, acinar, and papillary patterns, alongside a spindle cell component spreading along the pulmonary artery wall, resembling intimal sarcoma. The spindle tumor cells were positive for keratins, TTF-1, napsin A, and vimentin, but negative for p40, CK14, desmin, alpha-smooth muscle actin, CDK4, and MDM2. This profile indicates that the spindle cells originated from the adenocarcinoma cells via epithelial-mesenchymal transition. The vascular spread of pleomorphic carcinoma, mimicking pulmonary artery intimal sarcoma, represents an extremely rare mode of tumor invasion, which could be termed \"arterial carcinomatosis\". Immunohistochemical analysis is crucial for distinguishing pleomorphic carcinoma from coexisting intimal sarcoma, as the latter's prognosis is markedly poor.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"114-120"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952805","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":"Superoxide dismutase 2 deficiency in mesenchymal stromal cells induces sympathetic denervation and functional impairment of brown adipose tissue.","authors":"Yuya Urano, Shinji Mii, Shun Asai, Nobutoshi Esaki, Ryota Ando, Yukihiro Shiraki, Tadashi Iida, Katsuhiro Kato, Mika Hori, Yoshitaka Hayashi, Takahiko Shimizu, Atsushi Enomoto","doi":"10.1111/pin.13503","DOIUrl":"10.1111/pin.13503","url":null,"abstract":"<p><p>Brown adipose tissue (BAT) is an energy-consuming organ, and its functional dysregulation contributes to the development of metabolic diseases and obesity. BAT function is regulated by the sympathetic nervous system but declines with age, which is partly caused by reduced sympathetic nerve fibers innervating BAT. Thus far, the role of mesenchymal stromal/stem cells in age-related BAT dysfunction remains unknown. Here, we show that BAT dysfunction may be induced by a defect in the antioxidant capacity of stromal cells that localize in and around the nerve fibers (perineurial cells) of BAT. These cells express Meflin, a marker of mesenchymal stromal/stem cells. Specific deletion of the antioxidant enzyme superoxide dismutase 2 in Meflin-lineage cells caused sympathetic denervation and whitening of BAT and its functional impairment, as exemplified by a decline in the fat oxidation rate during the daytime. This phenotype was accompanied by overexpression of the neurorepulsive factor semaphorin 3A in perineurial cells. Notably, Meflin-deficient mice exhibited resistance to doxorubicin-induced BAT dysfunction. These results highlight the role of Meflin<sup>+</sup> stromal cells, including perineurial cells, in maintaining BAT function and suggest that targeting BAT stromal cells provides a new avenue for improving BAT function.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"69-81"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932352","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":"Roles of osteoclasts in pathological conditions.","authors":"Sohei Kitazawa, Ryuma Haraguchi, Riko Kitazawa","doi":"10.1111/pin.13500","DOIUrl":"10.1111/pin.13500","url":null,"abstract":"<p><p>Bone is a unique organ crucial for locomotion, mineral metabolism, and hematopoiesis. It maintains homeostasis through a balance between bone formation by osteoblasts and bone resorption by osteoclasts, which is regulated by the basic multicellular unit (BMU). Abnormal bone metabolism arises from an imbalance in the BMU. Osteoclasts, derived from the monocyte-macrophage lineage, are regulated by the RANKL-RANK-OPG system, which is a key factor in osteoclast differentiation. RANKL activates osteoclasts through its receptor RANK, while OPG acts as a decoy receptor that inhibits RANKL. In trabecular bone, high turnover involves rapid bone formation and resorption, influenced by conditions such as malignancy and inflammatory cytokines that increase RANKL expression. Cortical bone remodeling, regulated by aged osteocytes expressing RANKL, is less understood, despite ongoing research into how Rett syndrome, characterized by MeCP2 abnormalities, affects RANKL expression. Balancing trabecular and cortical bone involves mechanisms that preserve cortical bone, despite overall bone mass reduction due to aging or oxidative stress. Research into genes like sFRP4, which modulates bone mass, highlights the complex regulation by BMUs. The roles of the RANKL-RANK-OPG system extend beyond bone, affecting processes such as aortic valve formation and temperature regulation, which highlight the interconnected nature of biological research.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"55-68"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864938","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":"Histopathological study of the localization/distribution of Fusobacterium nucleatum in esophageal cancer.","authors":"Iku Sasaki-Higashimoto, Fumiyoshi Fujishima, Hirotaka Ishida, Yusuke Taniyama, Yohei Ozawa, Tomohiro Nakamura, Naoki Nakaya, Chiaki Sato, Hiroshi Okamoto, Junichi Tsunokake, Atsushi Kunimitsu, Takeru Mozumi, Takashi Kamei, Takashi Suzuki","doi":"10.1111/pin.13505","DOIUrl":"10.1111/pin.13505","url":null,"abstract":"<p><p>Fusobacterium nucleatum is implicated in esophageal cancer; however, its distribution in esophageal cancer tissues remains unknown. This study aimed to clarify the presence and distribution of F. nucleatum in esophageal cancer tissues using fluorescence in situ hybridization (FISH). Tissues collected from 70 patients with esophageal squamous cell carcinoma were examined using FISH. Corresponding normal epithelium and metastatic lymph nodes were assessed. F. nucleatum was identified more frequently in esophageal cancer tissues than in the normal epithelium. F. nucleatum also showed significant correlation with factors associated with tumor progression, such as pT factor and tumor size. As tumor progression advanced, the area occupied by F. nucleatum gradually became larger. F. nucleatum positivity was observed around the deep edge of the tumor nest (border-dense type) or identified diffusely in the tumor nest (diffuse distributed type). Furthermore, F. nucleatum was observed in metastatic lymph nodes, lesions of venous invasion, and walls of veins in normal epithelium. In conclusion, we visualized F. nucleatum using FISH and identified different distribution patterns of F. nucleatum, highlighting the spot density of its presence in tumor tissues. Recognizing this quantitative change is pivotal for establishing F. nucleatum as a reliable biomarker.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"82-91"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932324","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}