首页 > 最新文献

The Journal of Pathology最新文献

英文 中文
AI-guided histopathology predicts brain metastasis in lung cancer patients 人工智能引导的组织病理学可预测肺癌患者的脑转移。
IF 7.3 2区 医学 Q1 ONCOLOGY
The Journal of Pathology
Pub Date : 2024-03-04 DOI: 10.1002/path.6263
Haowen Zhou, Mark Watson, Cory T Bernadt, Steven (Siyu) Lin, Chieh-yu Lin, Jon H Ritter, Alexander Wein, Simon Mahler, Sid Rawal, Ramaswamy Govindan, Changhuei Yang, Richard J Cote

Brain metastases can occur in nearly half of patients with early and locally advanced (stage I–III) non-small cell lung cancer (NSCLC). There are no reliable histopathologic or molecular means to identify those who are likely to develop brain metastases. We sought to determine if deep learning (DL) could be applied to routine H&E-stained primary tumor tissue sections from stage I–III NSCLC patients to predict the development of brain metastasis. Diagnostic slides from 158 patients with stage I–III NSCLC followed for at least 5 years for the development of brain metastases (Met+, 65 patients) versus no progression (Met−, 93 patients) were subjected to whole-slide imaging. Three separate iterations were performed by first selecting 118 cases (45 Met+, 73 Met−) to train and validate the DL algorithm, while 40 separate cases (20 Met+, 20 Met−) were used as the test set. The DL algorithm results were compared to a blinded review by four expert pathologists. The DL-based algorithm was able to distinguish the eventual development of brain metastases with an accuracy of 87% (p < 0.0001) compared with an average of 57.3% by the four pathologists and appears to be particularly useful in predicting brain metastases in stage I patients. The DL algorithm appears to focus on a complex set of histologic features. DL-based algorithms using routine H&E-stained slides may identify patients who are likely to develop brain metastases from those who will remain disease free over extended (>5 year) follow-up and may thus be spared systemic therapy. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

近一半的早期和局部晚期（I-III 期）非小细胞肺癌（NSCLC）患者会发生脑转移。目前还没有可靠的组织病理学或分子学方法来识别那些可能发生脑转移的患者。我们试图确定深度学习（DL）能否应用于 I-III 期 NSCLC 患者的常规 H&E 染色原发肿瘤组织切片，以预测脑转移的发生。我们对 158 名 I-III 期 NSCLC 患者的诊断切片进行了全切片成像，这些患者至少随访了 5 年，发现脑转移（Met+，65 名患者）与无进展（Met-，93 名患者）。首先选择 118 个病例（45 个 Met+ ，73 个 Met- ）进行训练和验证 DL 算法，然后分别选择 40 个病例（20 个 Met+ ，20 个 Met- ）作为测试集，进行了三次迭代。将 DL 算法结果与四位病理专家的盲审结果进行比较。基于DL的算法能够区分脑转移瘤的最终发展，准确率高达87%（p 5年），因此可以避免系统性治疗。© 2024 作者。病理学杂志》由约翰威利父子有限公司代表大不列颠及爱尔兰病理学会出版。
{"title":"AI-guided histopathology predicts brain metastasis in lung cancer patients","authors":"Haowen Zhou,&nbsp;Mark Watson,&nbsp;Cory T Bernadt,&nbsp;Steven (Siyu) Lin,&nbsp;Chieh-yu Lin,&nbsp;Jon H Ritter,&nbsp;Alexander Wein,&nbsp;Simon Mahler,&nbsp;Sid Rawal,&nbsp;Ramaswamy Govindan,&nbsp;Changhuei Yang,&nbsp;Richard J Cote","doi":"10.1002/path.6263","DOIUrl":"10.1002/path.6263","url":null,"abstract":"<p>Brain metastases can occur in nearly half of patients with early and locally advanced (stage I–III) non-small cell lung cancer (NSCLC). There are no reliable histopathologic or molecular means to identify those who are likely to develop brain metastases. We sought to determine if deep learning (DL) could be applied to routine H&amp;E-stained primary tumor tissue sections from stage I–III NSCLC patients to predict the development of brain metastasis. Diagnostic slides from 158 patients with stage I–III NSCLC followed for at least 5 years for the development of brain metastases (Met<sup>+</sup>, 65 patients) versus no progression (Met<sup>−</sup>, 93 patients) were subjected to whole-slide imaging. Three separate iterations were performed by first selecting 118 cases (45 Met<sup>+</sup>, 73 Met<sup>−</sup>) to train and validate the DL algorithm, while 40 separate cases (20 Met<sup>+</sup>, 20 Met<sup>−</sup>) were used as the test set. The DL algorithm results were compared to a blinded review by four expert pathologists. The DL-based algorithm was able to distinguish the eventual development of brain metastases with an accuracy of 87% (<i>p</i> &lt; 0.0001) compared with an average of 57.3% by the four pathologists and appears to be particularly useful in predicting brain metastases in stage I patients. The DL algorithm appears to focus on a complex set of histologic features. DL-based algorithms using routine H&amp;E-stained slides may identify patients who are likely to develop brain metastases from those who will remain disease free over extended (&gt;5 year) follow-up and may thus be spared systemic therapy. © 2024 The Authors. <i>The Journal of Pathology</i> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 1","pages":"89-98"},"PeriodicalIF":7.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140020475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
List of Reviewers 审查员名单
IF 7.3 2区 医学 Q1 ONCOLOGY
The Journal of Pathology
Pub Date : 2024-03-04 DOI: 10.1002/path.6269
<p>The high quality of manuscripts published in <i>The Journal of Pathology</i> largely relies on the standards set by our expert reviewers. <i>The Journal of Pathology</i> wishes to thank the following 541 individuals who assisted by reviewing articles for the Journal in 2023 (affiliations shown are those currently held in our system).</p><p>Catherine Abbott, University of Edinburgh, Edinburgh, UK.</p><p>Balazs Acs, Karolinska Institutet, Stockholm, Sweden.</p><p>Alejandro Adam, Albany Medical College, Albany, NY, USA.</p><p>Rosalyn Adam, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.</p><p>Rahul Aggarwal, University of California San Francisco, San Francisco, CA, USA.</p><p>Saif S Ahmad, CRUK Cambridge Centre, Cambridge, UK.</p><p>Jared Ahrendsen, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</p><p>Katherine M Aird, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.</p><p>Rannar Airik, Medizinische Hochschule Hannover, Hannover, Germany.</p><p>Hikmat Al-Ahmadie, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.</p><p>Hana Algul, Klinikum rechts der Isar der Technischen Universitat München, München, Germany.</p><p>Malcolm Alison, Barts and the London School of Medicine & Dentistry, The Royal London Hospital, London, UK.</p><p>Alhadi Almangush, Helsingin yliopisto Haartman-instituutti, Helsinki, Finland.</p><p>Kristian Almstrup, Rigshospitalet, Kobenhavn, Denmark.</p><p>Cristina Amaral, Faculty of Pharmacy, University of Porto, Porto, Portugal.</p><p>Brage S Andresen, University of Southern Denmark, Odense, Denmark.</p><p>Corrado Angelini, University of Padova, Padova, Veneto, Italy.</p><p>David Assis, Yale School of Medicine, New Haven, CT, USA.</p><p>Radhika Atit, Case Western Reserve University, Cleveland, OH, USA.</p><p>Matias Avila, University of Navarra, Pamplona, Spain.</p><p>George Baillie, University of Glasgow, Glasgow, UK.</p><p>Holly Barker, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.</p><p>Sonali Barwe, Nemours Children's Hospital Delaware, Wilmington, DE, USA.</p><p>Ali Bashashati, British Columbia Cancer Agency, Vancouver, BC, Canada.</p><p>David P Basile, Indiana University School of Medicine, Indianapolis, IN, USA.</p><p>M Albert Basson, Kings College London, London, UK.</p><p>Adrian Bateman, University Hospital Southampton NHS Foundation Trust, Southampton, UK.</p><p>Daniel Baumhoer, University Hospital Basel, Basel, Switzerland.</p><p>Jan Becker, University Hospital of Cologne, Cologne, Germany.</p><p>Andrew Beggs, University of Birmingham, Birmingham, UK.</p><p>Jurgen Behrens, University Erlangen, Erlangen, Germany.</p><p>Hannah Beird, University of Texas MD Anderson Cancer Center, Houston, TX, USA.</p><p>Susan Bellis, University of Alabama, Birmingham, AL, USA.</p><p>Dorina Belotti, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.</p><p>Don Benjamin, University of Basel, Basel, Switzerland.</p><p>J
Adrienne Flanagan，英国伦敦，伦敦大学学院；Jean-Philippe Foy，法国巴黎，Pitié-Salpêtrière医院；Javier Francisco-Morcillo，西班牙埃斯特雷马杜拉，巴达霍斯，埃斯特雷马杜拉科学院；Diego Franco，西班牙哈恩，哈恩大学社会科学和法学系。Alexander Frankell，英国伦敦弗朗西斯-克里克研究所；Roberta Frapolli，意大利米兰马里奥-内格里；Theodore Friedman，美国加利福尼亚州洛杉矶加利福尼亚大学洛杉矶分校医学院；Karen Fritchie，美国俄亥俄州克利夫兰克利夫兰诊所；Morgan Fullerton，加拿大安大略省渥太华渥太华大学。Calum Gabbutt，英国伦敦巴兹癌症研究所；Lucia Gabriele，意大利罗马Istituto Superiore di Sanità；Umberto Galderisi，意大利那不勒斯坎帕尼亚 "Luigi Vanvitelli "大学；Richard Gallon，英国泰恩河畔纽卡斯尔纽卡斯尔大学；Marco Gaspari，英国马格纳大学医学系。Marco Gaspari，意大利卡坦扎罗 Magna Graecia 大学；Philippe Gaulard，法国克里特尔 Henry Mondor 医院；Emilio Geijo-Barrientos，西班牙阿利坎特 San Juan de Alicante Miguel Hernández de Elche 大学；Manfred Gessler，德国维尔茨堡 Theodor-Boveri-Institute 研究所。David Gewirtz，美国弗吉尼亚州里士满弗吉尼亚联邦大学医学药理学和毒理学学院。Blake Gilks，加拿大不列颠哥伦比亚大学医学系，加拿大不列颠哥伦比亚省温哥华。Vincent Goffin，Université Paris Cité，Paris，France.James Goldenring，Vanderbilt University，Nashville，TN，USA.Robert Goldin，ICSM at St Mary's，London，UK.Andrew Goldstein，University of California Los Angeles，Los Angeles，CA，USA.David Goode，Peter MacCallum Cancer Institute，Melbourne，VIC，Australia.Matthew Gorr，美国俄亥俄州立大学，俄亥俄州哥伦布市。Akiteru Goto，日本秋田县秋田大学。Patricia Grabowski，德国柏林 Charité Universitäts Medizin。Lakshman Gunaratnam，加拿大安大略省伦敦市西方大学舒立克医学院牙科学院。Patrick Ha，美国加利福尼亚大学旧金山分校。德国科隆，科隆大学医院。安德鲁-汉比（Andrew Hanby），英国利兹大学，利兹。Wolfgang Hartmann，德国明斯特，明斯特大学医院；Takashi Hashimoto，日本大阪，大阪都立大学；Martin Hasselblatt，德国明斯特，明斯特大学医院；Mark Hatley，美国田纳西州孟菲斯市，圣裘德儿童研究医院；Thierry Hauet，法国普瓦捷，普瓦捷大学。Lukas Hawinkels，荷兰莱顿，莱顿大学医学中心；Philip Hawkins，英国伦敦，国家淀粉样变性中心；Simon Hayward，美国伊利诺伊州埃文斯顿，北岸大学卫生系统研究所；Marcela Hernandez，智利圣地亚哥，智利大学牙科学院。Jochen Hess，德国海德堡，头颈肿瘤实验与转化中心；Ekkehard Hewer，瑞士洛桑，洛桑大学医院；Dominique Heymann，法国南特，南特大学；Friedhelm Hildebrandt，美国马萨诸塞州波士顿，哈佛医学院。Yoshihito Hirata，日本东京，东京大学医学科学研究所；Cheng-Ying Ho，美国马里兰州巴尔的摩，约翰霍普金斯大学医学院；Pancras Hogendoorn，荷兰莱顿，莱顿大学医学中心；Francis Hornicek，美国佛罗里达州迈阿密，迈阿密大学医学院。Ralph Hruban，美国马里兰州巴尔的摩市约翰霍普金斯大学医学院。Hsuan-Ying Huang，台湾高雄市长庚纪念医院-高雄医学中心。本-汉弗莱斯（Ben Humphreys），美国密苏里州圣路易斯市华盛顿大学医学院；戴维-亨茨曼（David Huntsman），加拿大不列颠哥伦比亚省温哥华市不列颠哥伦比亚省癌症研究中心；保拉-赫尔利（Paula Hurley），美国田纳西州纳什维尔市范德比尔特大学医学中心；佩尔-海布林（Per Hydbring），瑞典斯德哥尔摩卡罗林斯卡医学院。Robert Hynds，英国伦敦，伦敦大学学院儿童健康研究所；Arup K Indra，美国俄勒冈州科瓦利斯，俄勒冈州立大学；Masahiro Inoue，日本京都，京都大学研究生院医学系；Pietro Invernizzi，意大利米兰，Humanitas 临床与研究中心；Juan Iovanna，法国马赛，INSERM。 Jabed Iqbal，新加坡中央医院，新加坡，Select One；Clare Isacke，英国伦敦癌症研究所；Sachiko Iseki，日本东京医科齿科大学医科齿科研究生院；Takatsugu Ishimoto，日本熊本大学，熊本；Valerio Izzi，芬兰奥卢大学，奥卢；Sirpa Jalkanen，芬兰图尔库大学，图尔库；Marnix Jansen，英国伦敦大学学院医学院，伦敦。Valerio Izzi，芬兰奥卢，奥卢大学；Sirpa Jalkanen，芬兰图尔库，图尔库大学；Marnix Jansen，英国伦敦，伦敦大学学院医学院；Anne Jarry，法国南特，INSERM U1302；Shuai Jiang，美国新罕布什尔州汉诺威，达特茅斯学院盖瑟尔医学院。Karin Jirström, Lund University, Malmö, Sweden.Christian Jobin, University of Florida, Gainesville, FL, USA.Mohit Kumar Jolly, Indian Institute of Science, Bangalore, India.Russell Jones, Van Andel Institute, Grand Rapids, MI, USA.Diya Binoy Joseph，印度卡纳塔克邦班加罗尔干细胞科学和再生医学研究所。Rachid Karam，Ambry Genetics Corporation，Aliso Viejo，CA，USA.Nikos Karamanos，University of P
{"title":"List of Reviewers","authors":"","doi":"10.1002/path.6269","DOIUrl":"https://doi.org/10.1002/path.6269","url":null,"abstract":"&lt;p&gt;The high quality of manuscripts published in &lt;i&gt;The Journal of Pathology&lt;/i&gt; largely relies on the standards set by our expert reviewers. &lt;i&gt;The Journal of Pathology&lt;/i&gt; wishes to thank the following 541 individuals who assisted by reviewing articles for the Journal in 2023 (affiliations shown are those currently held in our system).&lt;/p&gt;&lt;p&gt;Catherine Abbott, University of Edinburgh, Edinburgh, UK.&lt;/p&gt;&lt;p&gt;Balazs Acs, Karolinska Institutet, Stockholm, Sweden.&lt;/p&gt;&lt;p&gt;Alejandro Adam, Albany Medical College, Albany, NY, USA.&lt;/p&gt;&lt;p&gt;Rosalyn Adam, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.&lt;/p&gt;&lt;p&gt;Rahul Aggarwal, University of California San Francisco, San Francisco, CA, USA.&lt;/p&gt;&lt;p&gt;Saif S Ahmad, CRUK Cambridge Centre, Cambridge, UK.&lt;/p&gt;&lt;p&gt;Jared Ahrendsen, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.&lt;/p&gt;&lt;p&gt;Katherine M Aird, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.&lt;/p&gt;&lt;p&gt;Rannar Airik, Medizinische Hochschule Hannover, Hannover, Germany.&lt;/p&gt;&lt;p&gt;Hikmat Al-Ahmadie, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.&lt;/p&gt;&lt;p&gt;Hana Algul, Klinikum rechts der Isar der Technischen Universitat München, München, Germany.&lt;/p&gt;&lt;p&gt;Malcolm Alison, Barts and the London School of Medicine &amp; Dentistry, The Royal London Hospital, London, UK.&lt;/p&gt;&lt;p&gt;Alhadi Almangush, Helsingin yliopisto Haartman-instituutti, Helsinki, Finland.&lt;/p&gt;&lt;p&gt;Kristian Almstrup, Rigshospitalet, Kobenhavn, Denmark.&lt;/p&gt;&lt;p&gt;Cristina Amaral, Faculty of Pharmacy, University of Porto, Porto, Portugal.&lt;/p&gt;&lt;p&gt;Brage S Andresen, University of Southern Denmark, Odense, Denmark.&lt;/p&gt;&lt;p&gt;Corrado Angelini, University of Padova, Padova, Veneto, Italy.&lt;/p&gt;&lt;p&gt;David Assis, Yale School of Medicine, New Haven, CT, USA.&lt;/p&gt;&lt;p&gt;Radhika Atit, Case Western Reserve University, Cleveland, OH, USA.&lt;/p&gt;&lt;p&gt;Matias Avila, University of Navarra, Pamplona, Spain.&lt;/p&gt;&lt;p&gt;George Baillie, University of Glasgow, Glasgow, UK.&lt;/p&gt;&lt;p&gt;Holly Barker, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.&lt;/p&gt;&lt;p&gt;Sonali Barwe, Nemours Children's Hospital Delaware, Wilmington, DE, USA.&lt;/p&gt;&lt;p&gt;Ali Bashashati, British Columbia Cancer Agency, Vancouver, BC, Canada.&lt;/p&gt;&lt;p&gt;David P Basile, Indiana University School of Medicine, Indianapolis, IN, USA.&lt;/p&gt;&lt;p&gt;M Albert Basson, Kings College London, London, UK.&lt;/p&gt;&lt;p&gt;Adrian Bateman, University Hospital Southampton NHS Foundation Trust, Southampton, UK.&lt;/p&gt;&lt;p&gt;Daniel Baumhoer, University Hospital Basel, Basel, Switzerland.&lt;/p&gt;&lt;p&gt;Jan Becker, University Hospital of Cologne, Cologne, Germany.&lt;/p&gt;&lt;p&gt;Andrew Beggs, University of Birmingham, Birmingham, UK.&lt;/p&gt;&lt;p&gt;Jurgen Behrens, University Erlangen, Erlangen, Germany.&lt;/p&gt;&lt;p&gt;Hannah Beird, University of Texas MD Anderson Cancer Center, Houston, TX, USA.&lt;/p&gt;&lt;p&gt;Susan Bellis, University of Alabama, Birmingham, AL, USA.&lt;/p&gt;&lt;p&gt;Dorina Belotti, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.&lt;/p&gt;&lt;p&gt;Don Benjamin, University of Basel, Basel, Switzerland.&lt;/p&gt;&lt;p&gt;J","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"262 4","pages":"529-538"},"PeriodicalIF":7.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140031855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma KAT8/SIRT7介导的Fascin-K41乙酰化/去乙酰化调节食管鳞状细胞癌的肿瘤转移。
IF 7.3 2区 医学 Q1 ONCOLOGY
The Journal of Pathology
Pub Date : 2024-02-27 DOI: 10.1002/path.6261
Da-Jia Li, Yin-Wei Cheng, Jin-Mei Pan, Zhen-Chang Guo, Shao-Hong Wang, Qing-Feng Huang, Ping-Juan Nie, Wen-Qi Shi, Xiu-E Xu, Bing Wen, Jin-Ling Zhong, Zhi-Da Zhang, Zhi-Yong Wu, Hui Zhao, Lian-Di Liao, Jian-Yi Wu, Kai Zhang, Geng Dong, En-Min Li, Li-Yan Xu

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Fascin 肌动蛋白捆绑蛋白1（Fascin）在包括食管鳞状细胞癌（ESCC）在内的多种癌症中高度表达，它是一种重要的致癌蛋白，通过捆绑F-肌动蛋白促进丝状嵴和侵袭嵴的形成，从而促进癌细胞的迁移和侵袭。然而，目前还不清楚 Fascin 的功能在癌细胞中究竟是如何受乙酰化调控的。在这里，组蛋白乙酰转移酶KAT8催化了ESCC细胞中Fascin赖氨酸41（K41）的乙酰化，从而抑制了Fascin介导的F-肌动蛋白捆绑以及丝状嵴和内陷嵴的形成。此外，NAD依赖性蛋白去乙酰化酶sirtuin（SIRT）7介导的Fascin-K41去乙酰化增强了丝状体和侵袭体的形成，从而促进了ESCC细胞的迁移和侵袭。临床上，对 ESCC 患者的癌组织和邻近组织样本的分析表明，淋巴结转移患者的癌组织中 Fascin-K41 乙酰化水平低于无淋巴结转移的患者，而低水平的 Fascin-K41 乙酰化与 ESCC 患者较差的预后有关。重要的是，K41乙酰化对目前正在临床评估的Fascin抑制剂之一NP-G2-044有明显的阻断作用，这表明NP-G2-044可能更适合Fascin-K41乙酰化水平低的患者，但不适合Fascin-K41乙酰化水平高的患者。© 2024 大不列颠及爱尔兰病理学会。John Wiley & Sons, Ltd.出版。
{"title":"KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma","authors":"Da-Jia Li,&nbsp;Yin-Wei Cheng,&nbsp;Jin-Mei Pan,&nbsp;Zhen-Chang Guo,&nbsp;Shao-Hong Wang,&nbsp;Qing-Feng Huang,&nbsp;Ping-Juan Nie,&nbsp;Wen-Qi Shi,&nbsp;Xiu-E Xu,&nbsp;Bing Wen,&nbsp;Jin-Ling Zhong,&nbsp;Zhi-Da Zhang,&nbsp;Zhi-Yong Wu,&nbsp;Hui Zhao,&nbsp;Lian-Di Liao,&nbsp;Jian-Yi Wu,&nbsp;Kai Zhang,&nbsp;Geng Dong,&nbsp;En-Min Li,&nbsp;Li-Yan Xu","doi":"10.1002/path.6261","DOIUrl":"10.1002/path.6261","url":null,"abstract":"<p>Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 1","pages":"74-88"},"PeriodicalIF":7.3,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression 丝氨酸/苏氨酸蛋白激酶D2-介导的DSG2苏氨酸730磷酸化促进食管鳞状细胞癌的进展。
IF 7.3 2区 医学 Q1 ONCOLOGY
The Journal of Pathology
Pub Date : 2024-02-27 DOI: 10.1002/path.6264
Yin-Qiao Liu, Yi-Wei Xu, Zheng-Tan Zheng, Die Li, Chao-Qun Hong, Hao-Qiang Dai, Jun-Hao Wang, Ling-Yu Chu, Lian-Di Liao, Hai-Ying Zou, En-Min Li, Jian-Jun Xie, Wang-Kai Fang

Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell–cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.

Desmoglein-2（DSG2）是一种跨膜糖蛋白，属于desmosomal cadherin家族，它介导细胞-细胞连接，调节细胞增殖、迁移和侵袭，促进肿瘤发生和转移。我们以前曾发现血清 DSG2 是诊断食管鳞状细胞癌（ESCC）的潜在生物标志物，但其意义和潜在的分子机制尚未确定。在这里，我们发现与邻近组织相比，ESCC组织中的DSG2有所增加。此外，我们还发现 DSG2 促进了 ESCC 细胞的迁移和侵袭。此外，通过相互作用组分析，我们发现丝氨酸/苏氨酸蛋白激酶D2（PRKD2）是一种新型的DSG2激酶，它介导DSG2在苏氨酸730（T730）处的磷酸化。在功能上，DSG2促进ESCC细胞迁移和侵袭依赖于DSG2-T730磷酸化。从机制上讲，DSG2 T730磷酸化激活了表皮生长因子受体、Src、AKT和ERK信号通路。此外，DSG2和PRKD2呈正相关，DSG2和PRKD2水平高的ESCC患者的总生存时间比DSG2和PRKD2水平低的患者短。综上所述，PRKD2是一种新型的DSG2激酶，PRKD2介导的DSG2 T730磷酸化促进了ESCC的进展。这些发现可能有助于未来开发针对DSG2和DSG2磷酸化的治疗药物。© 2024 大不列颠及爱尔兰病理学会。
{"title":"Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression","authors":"Yin-Qiao Liu,&nbsp;Yi-Wei Xu,&nbsp;Zheng-Tan Zheng,&nbsp;Die Li,&nbsp;Chao-Qun Hong,&nbsp;Hao-Qiang Dai,&nbsp;Jun-Hao Wang,&nbsp;Ling-Yu Chu,&nbsp;Lian-Di Liao,&nbsp;Hai-Ying Zou,&nbsp;En-Min Li,&nbsp;Jian-Jun Xie,&nbsp;Wang-Kai Fang","doi":"10.1002/path.6264","DOIUrl":"10.1002/path.6264","url":null,"abstract":"<p>Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell–cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 1","pages":"99-112"},"PeriodicalIF":7.3,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hourglass, a compass navigating global and regional heterogeneity of pancreatic cancer† 沙漏，胰腺癌全球和区域异质性的指南针†。
IF 7.3 2区 医学 Q1 ONCOLOGY
The Journal of Pathology
Pub Date : 2024-02-25 DOI: 10.1002/path.6268
Derya Bakırdöğen, Kıvanç Görgülü, Hana Algül

Advances in the digital pathology field have facilitated the characterization of histology samples for both clinical and preclinical research. However, uncovering subtle correlations between bioimaging, clinical and molecular parameters requires extensive statistical analysis. As a user-friendly software, Hourglass, simplifies multiparametric dataset analysis through intuitive data visualization and statistical tools. Systemic analysis of interleukin-6 (IL-6)/pStat3 signaling pathway through Hourglass revealed differences in regional immune cell composition within tumors. Moreover, these regional disparities were partially mediated by sex. Overall, Hourglass simplifies information extraction from complex datasets, resolving overlooked regional and global spatial tumor differences. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

数字病理学领域的进步促进了临床和临床前研究中组织学样本的特征描述。然而，发现生物成像、临床和分子参数之间的微妙关联需要大量的统计分析。作为一款用户友好型软件，Hourglass 通过直观的数据可视化和统计工具简化了多参数数据集分析。通过 Hourglass 对白细胞介素-6（IL-6）/pStat3 信号通路的系统分析，发现了肿瘤内区域免疫细胞组成的差异。此外，这些区域差异部分是由性别介导的。总之，Hourglass 简化了复杂数据集的信息提取，解决了被忽视的区域和全球肿瘤空间差异问题。© 2024 作者。病理学杂志》由 John Wiley & Sons Ltd 代表大不列颠及爱尔兰病理学会出版。
{"title":"Hourglass, a compass navigating global and regional heterogeneity of pancreatic cancer†","authors":"Derya Bakırdöğen,&nbsp;Kıvanç Görgülü,&nbsp;Hana Algül","doi":"10.1002/path.6268","DOIUrl":"10.1002/path.6268","url":null,"abstract":"<p>Advances in the digital pathology field have facilitated the characterization of histology samples for both clinical and preclinical research. However, uncovering subtle correlations between bioimaging, clinical and molecular parameters requires extensive statistical analysis. As a user-friendly software, Hourglass, simplifies multiparametric dataset analysis through intuitive data visualization and statistical tools. Systemic analysis of interleukin-6 (IL-6)/pStat3 signaling pathway through Hourglass revealed differences in regional immune cell composition within tumors. Moreover, these regional disparities were partially mediated by sex. Overall, Hourglass simplifies information extraction from complex datasets, resolving overlooked regional and global spatial tumor differences. © 2024 The Authors. <i>The Journal of Pathology</i> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 1","pages":"5-7"},"PeriodicalIF":7.3,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139969359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cellular and molecular characteristics of stromal Lkb1 deficiency-induced gastrointestinal polyposis based on single-cell RNA sequencing 基于单细胞 RNA 测序的基质 Lkb1 缺乏症诱发的胃肠道息肉病的细胞和分子特征。
IF 7.3 2区 医学 Q1 ONCOLOGY
The Journal of Pathology
Pub Date : 2024-02-23 DOI: 10.1002/path.6259
Zhaohua Cai, Yangjing Jiang, Huan Tong, Min Liang, Yijie Huang, Liang Fang, Feng Liang, Yunwen Hu, Xin Shi, Jian Wang, Zi Wang, Qingqi Ji, Huanhuan Huo, Linghong Shen, Ben He

Liver kinase B1 (Lkb1), encoded by serine/threonine kinase (Stk11), is a serine/threonine kinase and tumor suppressor that is strongly implicated in Peutz–Jeghers syndrome (PJS). Numerous studies have shown that mesenchymal-specific Lkb1 is sufficient for the development of PJS-like polyps in mice. However, the cellular origin and components of these Lkb1-associated polyps and underlying mechanisms remain elusive. In this study, we generated tamoxifen-inducible Lkb1flox/flox;Myh11-Cre/ERT2 and Lkb1flox/flox;PDGFRα-Cre/ERT2 mice, performed single-cell RNA sequencing (scRNA-seq) and imaging-based lineage tracing, and aimed to investigate the cellular complexity of gastrointestinal polyps associated with PJS. We found that Lkb1flox/+;Myh11-Cre/ERT2 mice developed gastrointestinal polyps starting at 9 months after tamoxifen treatment. scRNA-seq revealed aberrant stem cell-like characteristics of epithelial cells from polyp tissues of Lkb1flox/+;Myh11-Cre/ERT2 mice. The Lkb1-associated polyps were further characterized by a branching smooth muscle core, abundant extracellular matrix deposition, and high immune cell infiltration. In addition, the Spp1–Cd44 or Spp1–Itga8/Itgb1 axes were identified as important interactions among epithelial, mesenchymal, and immune compartments in Lkb1-associated polyps. These characteristics of gastrointestinal polyps were also demonstrated in another mouse model, tamoxifen-inducible Lkb1flox/flox;PDGFRα-Cre/ERT2 mice, which developed obvious gastrointestinal polyps as early as 2–3 months after tamoxifen treatment. Our findings further confirm the critical role of mesenchymal Lkb1/Stk11 in gastrointestinal polyposis and provide novel insight into the cellular complexity of Lkb1-associated polyp biology. © 2024 The Pathological Society of Great Britain and Ireland.

由丝氨酸/苏氨酸激酶（Stk11）编码的肝激酶 B1（Lkb1）是一种丝氨酸/苏氨酸激酶和肿瘤抑制因子，与 Peutz-Jeghers 综合征（PJS）密切相关。大量研究表明，间质特异性 Lkb1 足以导致小鼠出现 PJS 样息肉。然而，这些与 Lkb1 相关的息肉的细胞起源、组成成分和内在机制仍然难以捉摸。在这项研究中，我们培育了他莫昔芬诱导的Lkb1flox/flox ;Myh11-Cre/ERT2和Lkb1flox/flox ;PDGFRα-Cre/ERT2小鼠，进行了单细胞RNA测序（scRNA-seq）和基于成像的品系追踪，旨在研究与PJS相关的胃肠道息肉的细胞复杂性。我们发现，Lkb1flox/+ ;Myh11-Cre/ERT2小鼠在他莫昔芬治疗9个月后开始出现胃肠道息肉。scRNA-seq揭示了Lkb1flox/+ ;Myh11-Cre/ERT2小鼠息肉组织上皮细胞的异常干细胞样特征。Lkb1相关息肉的进一步特征是平滑肌核心分支、大量细胞外基质沉积和免疫细胞高度浸润。此外，Spp1-Cd44 或 Spp1-Itga8/Itgb1 轴被确定为 Lkb1 相关息肉中上皮细胞、间充质细胞和免疫细胞之间的重要相互作用。胃肠道息肉的这些特征在另一种小鼠模型中也得到了证实，即他莫昔芬诱导的 Lkb1flox/flox ;PDGFRα-Cre/ERT2 小鼠，这些小鼠在他莫昔芬治疗后 2-3 个月就出现了明显的胃肠道息肉。我们的研究结果进一步证实了间质 Lkb1/Stk11 在胃肠道息肉病中的关键作用，并对 Lkb1 相关息肉生物学的细胞复杂性提供了新的见解。© 2024 大不列颠及爱尔兰病理学会。
{"title":"Cellular and molecular characteristics of stromal Lkb1 deficiency-induced gastrointestinal polyposis based on single-cell RNA sequencing","authors":"Zhaohua Cai,&nbsp;Yangjing Jiang,&nbsp;Huan Tong,&nbsp;Min Liang,&nbsp;Yijie Huang,&nbsp;Liang Fang,&nbsp;Feng Liang,&nbsp;Yunwen Hu,&nbsp;Xin Shi,&nbsp;Jian Wang,&nbsp;Zi Wang,&nbsp;Qingqi Ji,&nbsp;Huanhuan Huo,&nbsp;Linghong Shen,&nbsp;Ben He","doi":"10.1002/path.6259","DOIUrl":"10.1002/path.6259","url":null,"abstract":"<p>Liver kinase B1 (Lkb1), encoded by serine/threonine kinase (<i>Stk11</i>), is a serine/threonine kinase and tumor suppressor that is strongly implicated in Peutz–Jeghers syndrome (PJS). Numerous studies have shown that mesenchymal-specific Lkb1 is sufficient for the development of PJS-like polyps in mice. However, the cellular origin and components of these Lkb1-associated polyps and underlying mechanisms remain elusive. In this study, we generated tamoxifen-inducible <i>Lkb1</i><sup><i>flox/flox</i></sup>;<i>Myh11-Cre/ERT2</i> and <i>Lkb1</i><sup><i>flox/flox</i></sup>;<i>PDGFRα-Cre/ERT2</i> mice, performed single-cell RNA sequencing (scRNA-seq) and imaging-based lineage tracing, and aimed to investigate the cellular complexity of gastrointestinal polyps associated with PJS. We found that <i>Lkb1</i><sup><i>flox/+</i></sup>;<i>Myh11-Cre/ERT2</i> mice developed gastrointestinal polyps starting at 9 months after tamoxifen treatment. scRNA-seq revealed aberrant stem cell-like characteristics of epithelial cells from polyp tissues of <i>Lkb1</i><sup><i>flox/+</i></sup>;<i>Myh11-Cre/ERT2</i> mice. The Lkb1-associated polyps were further characterized by a branching smooth muscle core, abundant extracellular matrix deposition, and high immune cell infiltration. In addition, the Spp1–Cd44 or Spp1–Itga8/Itgb1 axes were identified as important interactions among epithelial, mesenchymal, and immune compartments in Lkb1-associated polyps. These characteristics of gastrointestinal polyps were also demonstrated in another mouse model, tamoxifen-inducible <i>Lkb1</i><sup><i>flox/flox</i></sup>;<i>PDGFRα-Cre/ERT2</i> mice, which developed obvious gastrointestinal polyps as early as 2–3 months after tamoxifen treatment. Our findings further confirm the critical role of mesenchymal <i>Lkb1/Stk11</i> in gastrointestinal polyposis and provide novel insight into the cellular complexity of Lkb1-associated polyp biology. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 1","pages":"47-60"},"PeriodicalIF":7.3,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TP53 disruptive mutation predicts platinum-based chemotherapy and PD-1/PD-L1 blockade response in urothelial carcinoma TP53破坏性突变可预测铂类化疗和PD-1/PD-L1阻断剂对尿路上皮癌的反应。
IF 7.3 2区 医学 Q1 ONCOLOGY
The Journal of Pathology
Pub Date : 2024-02-21 DOI: 10.1002/path.6266
Kaifeng Jin, Jingtong Xu, Xiaohe Su, Ziyue Xu, Bingyu Li, Ge Liu, Hailong Liu, Yiwei Wang, Yu Zhu, Le Xu, Weijuan Zhang, Zhaopei Liu, Zewei Wang, Yuan Chang, Jiejie Xu

TP53 mutation is one of the most common genetic alterations in urothelial carcinoma (UrCa), and heterogeneity of TP53 mutants leads to heterogeneous clinical outcomes. This study aimed to investigate the clinical relevance of specific TP53 mutations in UrCa. In this study, a total of eight cohorts were enrolled, along with matched clinical annotation. TP53 mutations were classified as disruptive and nondisruptive according to the degree of disturbance of p53 protein function and structure. We evaluated the clinical significance of TP53 mutations in our local datasets and publicly available datasets. The co-occurring events of TP53 mutations in UrCa, along with their therapeutic indications, functional effects, and the tumor immune microenvironment, were also investigated. TP53 mutations were identified in 49.7% of the UrCa patients. Within this group, 25.1% of patients carried TP53Disruptive mutations, a genetic alteration correlated with a significantly poorer overall survival (OS) when compared to individuals with TP53Nondisruptive mutations and those with wild-type TP53. Significantly, patients with TP53Disruptive mutations exhibit an increased probability of responding favorably to PD-1/PD-L1 blockade and chemoimmunotherapy. Meanwhile, there was no noteworthy distinction in OS among patients with varying TP53 mutation status who underwent chemotherapy. Samples with TP53Disruptive mutations showed an enriched APOBEC- and POLE-related mutational signature, as well as an elevated tumor mutation burden. The sensitivity to immunotherapy in tumors carrying TP53Disruptive mutation may be attributed to the inflamed tumor microenvironment characterized by increased CD8+T cell infiltration and interferon-gamma signaling activation. In conclusion, UrCa patients with TP53Disruptive mutations have shown reduced survival rates, yet they may respond well to PD-1/PD-L1 blockade therapy and chemoimmunotherapy. By distinguishing specific TP53 mutations, we can improve risk stratification and offer personalized genomics-guided therapy to UrCa patients. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

TP53突变是尿路上皮癌（UrCa）最常见的基因改变之一，TP53突变体的异质性导致了不同的临床结果。本研究旨在探讨特定TP53突变在尿路癌中的临床意义。本研究共纳入了八个队列，并进行了匹配的临床注释。根据p53蛋白功能和结构的紊乱程度，TP53突变被分为破坏性和非破坏性突变。我们评估了本地数据集和公开数据集中 TP53 突变的临床意义。我们还研究了TP53突变在UrCa中的并发症及其治疗适应症、功能效应和肿瘤免疫微环境。49.7%的UrCa患者发现了TP53突变。在这一群体中，25.1%的患者携带TP53破坏性突变，与TP53非破坏性突变和野生型TP53患者相比，这种基因改变与较差的总生存期（OS）相关。值得注意的是，TP53Disruptive突变患者对PD-1/PD-L1阻断和化疗免疫疗法产生良好反应的概率增加。同时，在接受化疗的不同TP53突变状态的患者中，OS没有明显的区别。具有TP53破坏性突变的样本显示出丰富的APOBEC和POLE相关突变特征，以及较高的肿瘤突变负荷。携带 TP53Disruptive 突变的肿瘤对免疫疗法的敏感性可能归因于以 CD8+ T 细胞浸润增加和干扰素-γ 信号激活为特征的炎症肿瘤微环境。总之，具有 TP53Disruptive 突变的 UrCa 患者生存率降低，但他们可能对 PD-1/PD-L1 阻断疗法和化学免疫疗法反应良好。通过区分特定的TP53突变，我们可以改善风险分层，并为UrCa患者提供个性化的基因组指导治疗。© 2024 作者。病理学杂志》由 John Wiley & Sons Ltd 代表大不列颠及爱尔兰病理学会出版。
{"title":"TP53 disruptive mutation predicts platinum-based chemotherapy and PD-1/PD-L1 blockade response in urothelial carcinoma","authors":"Kaifeng Jin,&nbsp;Jingtong Xu,&nbsp;Xiaohe Su,&nbsp;Ziyue Xu,&nbsp;Bingyu Li,&nbsp;Ge Liu,&nbsp;Hailong Liu,&nbsp;Yiwei Wang,&nbsp;Yu Zhu,&nbsp;Le Xu,&nbsp;Weijuan Zhang,&nbsp;Zhaopei Liu,&nbsp;Zewei Wang,&nbsp;Yuan Chang,&nbsp;Jiejie Xu","doi":"10.1002/path.6266","DOIUrl":"10.1002/path.6266","url":null,"abstract":"<p><i>TP53</i> mutation is one of the most common genetic alterations in urothelial carcinoma (UrCa), and heterogeneity of <i>TP53</i> mutants leads to heterogeneous clinical outcomes. This study aimed to investigate the clinical relevance of specific <i>TP53</i> mutations in UrCa. In this study, a total of eight cohorts were enrolled, along with matched clinical annotation. <i>TP53</i> mutations were classified as disruptive and nondisruptive according to the degree of disturbance of p53 protein function and structure. We evaluated the clinical significance of <i>TP53</i> mutations in our local datasets and publicly available datasets. The co-occurring events of <i>TP53</i> mutations in UrCa, along with their therapeutic indications, functional effects, and the tumor immune microenvironment, were also investigated. <i>TP53</i> mutations were identified in 49.7% of the UrCa patients. Within this group, 25.1% of patients carried <i>TP53</i><sup>Disruptive</sup> mutations, a genetic alteration correlated with a significantly poorer overall survival (OS) when compared to individuals with <i>TP53</i><sup>Nondisruptive</sup> mutations and those with wild-type <i>TP53</i>. Significantly, patients with <i>TP53</i><sup>Disruptive</sup> mutations exhibit an increased probability of responding favorably to PD-1/PD-L1 blockade and chemoimmunotherapy. Meanwhile, there was no noteworthy distinction in OS among patients with varying <i>TP53</i> mutation status who underwent chemotherapy. Samples with <i>TP53</i><sup>Disruptive</sup> mutations showed an enriched APOBEC- and POLE-related mutational signature, as well as an elevated tumor mutation burden. The sensitivity to immunotherapy in tumors carrying <i>TP53</i><sup>Disruptive</sup> mutation may be attributed to the inflamed tumor microenvironment characterized by increased CD8<sup>+</sup>T cell infiltration and interferon-gamma signaling activation. In conclusion, UrCa patients with <i>TP53</i><sup>Disruptive</sup> mutations have shown reduced survival rates, yet they may respond well to PD-1/PD-L1 blockade therapy and chemoimmunotherapy. By distinguishing specific <i>TP53</i> mutations, we can improve risk stratification and offer personalized genomics-guided therapy to UrCa patients. © 2024 The Authors. <i>The Journal of Pathology</i> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 2","pages":"139-149"},"PeriodicalIF":7.3,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139911704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New analysis of atypical spermatocytic tumours reveals extensive heterogeneity and plasticity of germ cell tumours† 对非典型精原细胞瘤的新分析揭示了生殖细胞瘤的广泛异质性和可塑性†。
IF 7.3 2区 医学 Q1 ONCOLOGY
The Journal of Pathology
Pub Date : 2024-02-16 DOI: 10.1002/path.6262
Ewa Rajpert-De Meyts, Anne Goriely, Kristian Almstrup

Testicular germ cell tumours (TGCTs) derived from immature (type I) and pluripotent germ cell neoplasia in situ (GCNIS, type II) are characterised by remarkable phenotypic heterogeneity and plasticity. In contrast, the rare spermatocytic tumour (SpT, type III), derived from mature spermatogonia, is considered a homogenous and benign tumour but may occasionally present as an anaplastic or an aggressive sarcomatoid tumour. While various oncogenic processes had been proposed, the precise mechanism driving malignant progression remained elusive until the molecular characterisation of a series of atypical SpTs described in a recent issue of The Journal of Pathology. The emerging picture suggests the presence of two distinct trajectories for SpTs, involving either RAS/mitogen-activated protein kinase pathway mutations or a ploidy shift with secondary TP53 mutations and/or gain of chromosome 12p, the latter known as pathognomonic for type II GCNIS-derived TGCTs. Here, we discuss the implications of these findings, seen from the perspective of germ cell biology and the unique features of different TGCTs. The evolving phenotype of SpTs, induced by genomic and epigenetic changes, illustrates that the concept of plasticity applies to all germ cell tumours, making them inherently heterogenous and capable of significant transformation during progression. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

睾丸生殖细胞瘤（TGCT）来源于未成熟细胞（I 型）和多能生殖细胞原位肿瘤（GCNIS，II 型），具有显著的表型异质性和可塑性。相比之下，罕见的精原细胞瘤（SpT，III 型）源自成熟的精原细胞，被认为是一种同质性良性肿瘤，但偶尔也会表现为无性或侵袭性肉瘤。虽然人们提出了各种致癌过程，但在最近一期《病理学杂志》对一系列非典型 SpTs 进行分子鉴定之前，驱动恶性进展的确切机制仍然难以确定。新的研究结果表明，SpTs存在两种不同的发展轨迹，一种是RAS/介原激活蛋白激酶通路突变，另一种是伴有继发性TP53突变和/或染色体12p增益的倍性转移，后者被认为是II型GCNIS衍生型TGCTs的病理标志。在此，我们将从生殖细胞生物学的角度和不同 TGCT 的独特特征来讨论这些发现的意义。由基因组和表观遗传学变化诱导的 SpTs 表型不断演变，说明可塑性的概念适用于所有生殖细胞肿瘤，使它们具有内在的异质性，并能在发展过程中发生重大转变。© 2024 作者。病理学杂志》由约翰威利父子有限公司代表大不列颠及爱尔兰病理学会出版。
{"title":"New analysis of atypical spermatocytic tumours reveals extensive heterogeneity and plasticity of germ cell tumours†","authors":"Ewa Rajpert-De Meyts,&nbsp;Anne Goriely,&nbsp;Kristian Almstrup","doi":"10.1002/path.6262","DOIUrl":"10.1002/path.6262","url":null,"abstract":"<p>Testicular germ cell tumours (TGCTs) derived from immature (type I) and pluripotent germ cell neoplasia <i>in situ</i> (GCNIS, type II) are characterised by remarkable phenotypic heterogeneity and plasticity. In contrast, the rare spermatocytic tumour (SpT, type III), derived from mature spermatogonia, is considered a homogenous and benign tumour but may occasionally present as an anaplastic or an aggressive sarcomatoid tumour. While various oncogenic processes had been proposed, the precise mechanism driving malignant progression remained elusive until the molecular characterisation of a series of atypical SpTs described in a recent issue of <i>The Journal of Pathology.</i> The emerging picture suggests the presence of two distinct trajectories for SpTs, involving either RAS/mitogen-activated protein kinase pathway mutations or a ploidy shift with secondary <i>TP53</i> mutations and/or gain of chromosome 12p, the latter known as pathognomonic for type II GCNIS-derived TGCTs. Here, we discuss the implications of these findings, seen from the perspective of germ cell biology and the unique features of different TGCTs. The evolving phenotype of SpTs, induced by genomic and epigenetic changes, illustrates that the concept of plasticity applies to all germ cell tumours, making them inherently heterogenous and capable of significant transformation during progression. © 2024 The Authors. <i>The Journal of Pathology</i> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 1","pages":"1-4"},"PeriodicalIF":7.3,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139739997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrated analyses of the genetic and clinicopathological features of cholangiolocarcinoma: cholangiolocarcinoma may be characterized by mismatch-repair deficiency 综合分析胆管癌的遗传学和临床病理学特征：胆管癌的特征可能是错配修复缺陷。
IF 7.3 2区 医学 Q1 ONCOLOGY
The Journal of Pathology
Pub Date : 2024-02-16 DOI: 10.1002/path.6257
Kenta Makino, Takamichi Ishii, Haruhiko Takeda, Yoichi Saito, Yukio Fujiwara, Masakazu Fujimoto, Takashi Ito, Satoshi Wakama, Ken Kumagai, Fumiaki Munekage, Hiroshi Horie, Katsuhiro Tomofuji, Yu Oshima, Elena Yukie Uebayashi, Takayuki Kawai, Satoshi Ogiso, Ken Fukumitsu, Atsushi Takai, Hiroshi Seno, Etsuro Hatano

Cholangiolocarcinoma (CLC) is a primary liver carcinoma that resembles the canals of Hering and that has been reported to be associated with stem cell features. Due to its rarity, the nature of CLC remains unclear, and its pathological classification remains controversial. To clarify the positioning of CLC in primary liver cancers and identify characteristics that could distinguish CLC from other liver cancers, we performed integrated analyses using whole-exome sequencing (WES), immunohistochemistry, and a retrospective review of clinical information on eight CLC cases and two cases of recurrent CLC. WES demonstrated that CLC includes IDH1 and BAP1 mutations, which are characteristic of intrahepatic cholangiocarcinoma (iCCA). A mutational signature analysis showed a pattern similar to that of iCCA, which was different from that of hepatocellular carcinoma (HCC). CLC cells, including CK7, CK19, and EpCAM, were positive for cholangiocytic differentiation markers. However, the hepatocytic differentiation marker AFP and stem cell marker SALL4 were completely negative. The immunostaining patterns of CLC with CD56 and epithelial membrane antigen were similar to those of the noncancerous bile ductules. In contrast, mutational signature cluster analyses revealed that CLC formed a cluster associated with mismatch-repair deficiency (dMMR), which was separate from iCCA. Therefore, to evaluate MMR status, we performed immunostaining of four MMR proteins (PMS2, MSH6, MLH1, and MSH2) and detected dMMR in almost all CLCs. In conclusion, CLC had highly similar characteristics to iCCA but not to HCC. CLC can be categorized as a subtype of iCCA. In contrast, CLC has characteristics of dMMR tumors that are not found in iCCA, suggesting that it should be treated distinctly from iCCA. © 2024 The Pathological Society of Great Britain and Ireland.

胆管癌（Colangiolocarcinoma，CLC）是一种原发性肝癌，与赫林肝管相似，据报道与干细胞特征有关。由于其罕见性，胆管癌的性质仍不明确，其病理分类仍存在争议。为了明确CLC在原发性肝癌中的定位，并找出可将CLC与其他肝癌区分开来的特征，我们利用全外显子组测序（WES）、免疫组化以及对8例CLC病例和2例复发性CLC病例临床信息的回顾性分析进行了综合分析。全外显子组测序表明，CLC包括IDH1和BAP1突变，这是肝内胆管癌（iCCA）的特征。突变特征分析表明，CLC细胞的突变模式与肝内胆管癌（iCCA）相似，但与肝细胞癌（HCC）不同。CLC细胞（包括CK7、CK19和EpCAM）的胆管细胞分化标志物呈阳性。然而，肝细胞分化标志物 AFP 和干细胞标志物 SALL4 则完全阴性。CLC的CD56和上皮膜抗原免疫染色模式与非癌性胆管相似。相反，突变特征聚类分析显示，CLC形成了一个与错配修复缺陷（dMMR）相关的聚类，与iCCA分开。因此，为了评估MMR状态，我们对四种MMR蛋白（PMS2、MSH6、MLH1和MSH2）进行了免疫染色，结果在几乎所有的CLC中都检测到了dMMR。总之，CLC 具有与 iCCA 高度相似的特征，但与 HCC 并不相同。CLC可归类为iCCA的一个亚型。相比之下，CLC具有iCCA所没有的dMMR肿瘤特征，这表明它应与iCCA区别对待。© 2024 大不列颠及爱尔兰病理学会。
{"title":"Integrated analyses of the genetic and clinicopathological features of cholangiolocarcinoma: cholangiolocarcinoma may be characterized by mismatch-repair deficiency","authors":"Kenta Makino,&nbsp;Takamichi Ishii,&nbsp;Haruhiko Takeda,&nbsp;Yoichi Saito,&nbsp;Yukio Fujiwara,&nbsp;Masakazu Fujimoto,&nbsp;Takashi Ito,&nbsp;Satoshi Wakama,&nbsp;Ken Kumagai,&nbsp;Fumiaki Munekage,&nbsp;Hiroshi Horie,&nbsp;Katsuhiro Tomofuji,&nbsp;Yu Oshima,&nbsp;Elena Yukie Uebayashi,&nbsp;Takayuki Kawai,&nbsp;Satoshi Ogiso,&nbsp;Ken Fukumitsu,&nbsp;Atsushi Takai,&nbsp;Hiroshi Seno,&nbsp;Etsuro Hatano","doi":"10.1002/path.6257","DOIUrl":"10.1002/path.6257","url":null,"abstract":"<p>Cholangiolocarcinoma (CLC) is a primary liver carcinoma that resembles the canals of Hering and that has been reported to be associated with stem cell features. Due to its rarity, the nature of CLC remains unclear, and its pathological classification remains controversial. To clarify the positioning of CLC in primary liver cancers and identify characteristics that could distinguish CLC from other liver cancers, we performed integrated analyses using whole-exome sequencing (WES), immunohistochemistry, and a retrospective review of clinical information on eight CLC cases and two cases of recurrent CLC. WES demonstrated that CLC includes <i>IDH1</i> and <i>BAP1</i> mutations, which are characteristic of intrahepatic cholangiocarcinoma (iCCA). A mutational signature analysis showed a pattern similar to that of iCCA, which was different from that of hepatocellular carcinoma (HCC). CLC cells, including CK7, CK19, and EpCAM, were positive for cholangiocytic differentiation markers. However, the hepatocytic differentiation marker AFP and stem cell marker SALL4 were completely negative. The immunostaining patterns of CLC with CD56 and epithelial membrane antigen were similar to those of the noncancerous bile ductules. In contrast, mutational signature cluster analyses revealed that CLC formed a cluster associated with mismatch-repair deficiency (dMMR), which was separate from iCCA. Therefore, to evaluate MMR status, we performed immunostaining of four MMR proteins (PMS2, MSH6, MLH1, and MSH2) and detected dMMR in almost all CLCs. In conclusion, CLC had highly similar characteristics to iCCA but not to HCC. CLC can be categorized as a subtype of iCCA. In contrast, CLC has characteristics of dMMR tumors that are not found in iCCA, suggesting that it should be treated distinctly from iCCA. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 1","pages":"32-46"},"PeriodicalIF":7.3,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139739996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The spatial landscape of T cells in the microenvironment of stage III lung adenocarcinoma III 期肺癌微环境中 T 细胞的空间分布。
IF 7.3 2区 医学 Q1 ONCOLOGY
The Journal of Pathology
Pub Date : 2024-02-16 DOI: 10.1002/path.6254
Ziqing Zeng, Weijiao Du, Fan Yang, Zhenzhen Hui, Yunliang Wang, Peng Zhang, Xiying Zhang, Wenwen Yu, Xiubao Ren, Feng Wei

This study aimed to provide more information for prognostic stratification for patients through an analysis of the T-cell spatial landscape. It involved analyzing stained tissue sections of 80 patients with stage III lung adenocarcinoma (LUAD) using multiplex immunofluorescence and exploring the spatial landscape of T cells and their relationship with prognosis in the center of the tumor (CT) and invasive margin (IM). In this study, multivariate regression suggested that the relative clustering of CT CD4+ conventional T cell (Tconv) to inducible Treg (iTreg), natural regulatory T cell (nTreg) to Tconv, terminal CD8+ T cell (tCD8) to helper T cell (Th), and IM Treg to tCD8 and the relative dispersion of CT nTreg to iTreg, IM nTreg to nTreg were independent risk factors for DFS. Finally, we constructed a spatial immunological score named the GT score, which had stronger prognostic correlation than IMMUNOSCORE® based on CD3/CD8 cell densities. The spatial layout of T cells in the tumor microenvironment and the proposed GT score can reflect the prognosis of patients with stage III LUAD more effectively than T-cell density. The exploration of the T-cell spatial landscape may suggest potential cell–cell interactions and therapeutic targets and better guide clinical decision-making. © 2024 The Pathological Society of Great Britain and Ireland.

这项研究旨在通过分析T细胞的空间分布，为患者的预后分层提供更多信息。研究采用多重免疫荧光技术分析了80例III期肺腺癌（LUAD）患者的染色组织切片，探讨了肿瘤中心（CT）和浸润边缘（IM）的T细胞空间分布及其与预后的关系。在这项研究中，多变量回归表明，CT CD4+ 传统 T 细胞（Tconv）与诱导性 Treg（iTreg）、自然调节性 T 细胞（nTreg）与 Tconv、末端 CD8+ T 细胞（tCD8）与辅助性 T 细胞（Th）、IM Treg 与 tCD8 的相对聚集，以及 CT nTreg 与 iTreg、IM nTreg 与 nTreg 的相对分散是 DFS 的独立危险因素。最后，我们构建了一个名为GT评分的空间免疫学评分，它比基于CD3/CD8细胞密度的IMMUNOSCORE®具有更强的预后相关性。与T细胞密度相比，T细胞在肿瘤微环境中的空间布局和提出的GT评分能更有效地反映III期LUAD患者的预后。对T细胞空间格局的探索可能会提示潜在的细胞-细胞相互作用和治疗靶点，从而更好地指导临床决策。© 2024 大不列颠及爱尔兰病理学会。
{"title":"The spatial landscape of T cells in the microenvironment of stage III lung adenocarcinoma","authors":"Ziqing Zeng,&nbsp;Weijiao Du,&nbsp;Fan Yang,&nbsp;Zhenzhen Hui,&nbsp;Yunliang Wang,&nbsp;Peng Zhang,&nbsp;Xiying Zhang,&nbsp;Wenwen Yu,&nbsp;Xiubao Ren,&nbsp;Feng Wei","doi":"10.1002/path.6254","DOIUrl":"10.1002/path.6254","url":null,"abstract":"<p>This study aimed to provide more information for prognostic stratification for patients through an analysis of the T-cell spatial landscape. It involved analyzing stained tissue sections of 80 patients with stage III lung adenocarcinoma (LUAD) using multiplex immunofluorescence and exploring the spatial landscape of T cells and their relationship with prognosis in the center of the tumor (CT) and invasive margin (IM). In this study, multivariate regression suggested that the relative clustering of CT CD4<sup>+</sup> conventional T cell (Tconv) to inducible Treg (iTreg), natural regulatory T cell (nTreg) to Tconv, terminal CD8<sup>+</sup> T cell (tCD8) to helper T cell (Th), and IM Treg to tCD8 and the relative dispersion of CT nTreg to iTreg, IM nTreg to nTreg were independent risk factors for DFS. Finally, we constructed a spatial immunological score named the G<sub>T</sub> score, which had stronger prognostic correlation than IMMUNOSCORE® based on CD3/CD8 cell densities. The spatial layout of T cells in the tumor microenvironment and the proposed G<sub>T</sub> score can reflect the prognosis of patients with stage III LUAD more effectively than T-cell density. The exploration of the T-cell spatial landscape may suggest potential cell–cell interactions and therapeutic targets and better guide clinical decision-making. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"262 4","pages":"517-528"},"PeriodicalIF":7.3,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139739998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
首页 上一页 下一页 尾页
类型
全部 化学•材料 生命科学 医学 物理 工程技术 环境•农林 材料科学 地球科学 法学 管理学 化学 环境科学与生态学 计算机科学 教育学 经济学 农林科学 人文科学 生物学 数学 物理与天体物理 心理学 综合性期刊 其他 工业工程 理学 历史学 农学 文学 信息工程
数据库
全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley
期刊
The Journal of Pathology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
﹀
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整，为了账户安全，请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号：481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们：info@booksci.cn
Book学术提供免费学术资源搜索服务，方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1