Article
Biochemistry & Molecular Biology
Xiang Chen, Margaret Clement, M. John Hicks, Poonam Sarkar, M. Waleed Gaber, Tsz-Kwong Man
Summary: This study found that lysyl oxidase (LOX) expression was associated with cytoplasmic mislocalization of p27 in osteosarcoma. Higher LOX expression promoted cell proliferation, migration, and invasiveness, and resulted in pulmonary metastases. The upregulation of phospho-FAK was identified as the mechanism by which LOX promotes osteosarcoma metastasis. FAK inhibition may be a promising therapeutic strategy to reduce LOX-mediated metastasis in osteosarcoma.
Article
Cell Biology
Aitao Nai, Huihui Zeng, Qiong Wu, Zirui He, Shuwen Zeng, Shoaib Bashir, Feng Ma, Jie He, Wei Wan, Meng Xu
Summary: In this study, we found that overexpression of LOX in gastric carcinoma is associated with poor prognosis and may affect the development of gastric cancer through regulating the HIF1A-AS2/RP11-366L20.2-miR-29c axis, promoting M2 macrophage polarization, tumor immune escape, and enhancing drug resistance of tumor cells to chemotherapeutic drugs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Xin Yi, Yi Zhou, Yue Chen, Xin Feng, Chang Liu, Ding-Sheng Jiang, Jing Geng, Xiaoyan Li, Xuejun Jiang, Ze-Min Fang
Summary: The study revealed that LOXL2 and LOXL3 protein levels are upregulated in aortic dissection patients compared to non-AD subjects, while LOXL4 levels are downregulated and LOX and LOXL1 levels are comparable. LOXL2 regulates extracellular matrix in HASMCs, and LOXL3 inhibits HASMC proliferation, indicating their involvement in the pathological process of aortic dissection.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Endocrinology & Metabolism
Chun Luo, Chongyu Hu, Bingyang Li, Junyu Liu, Liming Hu, Rui Dong, Xin Liao, Jilin Zhou, Lu Xu, Songlin Liu, Yifeng Li, Dun Yuan, Weixi Jiang, Junxia Yan
Summary: The study found that LOX and LOXL2 gene polymorphisms were associated with the risk of single IA and multiple IA in a Chinese population, while SNPs of LOXL1, LOXL3, and LOXL4 were not associated with IA risk. Further investigation is needed to understand the effects of these genes on IA.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Matthew R. Aronoff, Paul Hiebert, Nina B. Hentzen, Sabine Werner, Helma Wennemers
Summary: Collagens are essential fibrous proteins for connective tissues, and lysyl oxidases play a crucial role in their cross-linking process. Abnormal LOX activity is associated with various diseases. The probe presented in this study can monitor and target LOX-mediated collagen cross-linking, potentially improving understanding of collagen remodeling and offering new opportunities for diagnosing fibrotic and malignant diseases.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Medicine, General & Internal
Jinfeng Zhu, Chen Luo, Jiefeng Zhao, Xiaojian Zhu, Kang Lin, Fanqin Bu, Zhonglin Yu, Feilong Zou, Zhengming Zhu
Summary: The study revealed that high expression of LOX in gastric cancer tissues is significantly associated with poor overall survival, LOX overexpression is closely correlated with T-stage progression in gastric cancer, and LOX is an independent factor affecting the prognosis of gastric cancer patients.
FRONTIERS IN MEDICINE
(2021)
Article
Oncology
Shireen Attaran, John J. Skoko, Barbara L. Hopkins, Megan K. Wright, Laurel E. Wood, Alparslan Asan, Hyun Ae Woo, Adam Feinberg, Carola A. Neumann
Summary: PRDX1 plays different roles in cancer progression, acting as a tumor suppressor in certain cell types while also being a potential drug target in cancer cell xenografts. The inactivation of PRDX1 in mammary fibroblasts promotes collagen remodelling and supports breast cancer progression. This study highlights the importance of PRDX1 protein levels in breast cancer cohorts for survival analysis.
BRITISH JOURNAL OF CANCER
(2021)
Article
Urology & Nephrology
Michael S. Leapman, Rong Wang, Stacy Loeb, Tyler M. Seibert, Franklin D. Gaylis, Ben Lowentritt, Gordon A. Brown, Ronald Chen, Daniel Lin, John Witte, Matthew R. Cooperberg, William J. Catalona, Cary P. Gross, Xiaomei Ma
Summary: It is unclear whether compliance with recommended monitoring tests has changed over time for patients with localized prostate cancer undergoing observation. A retrospective cohort study of Medicare beneficiaries diagnosed with low- or intermediate-risk prostate cancer in 2004-2016 was conducted to examine rates of PSA testing, prostate biopsy, and prostate MRI. The study found that usage of recommended monitoring tests remains low among patients managed with observation and that rates of PSA testing and biopsy have increased over time. Various factors including age, clinical risk, race/ethnicity, census tract poverty, and region were associated with testing rates.
JOURNAL OF UROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Talita de Sousa Laurentino, Roseli da Silva Soares, Suely Kazue Nagahashi Marie, Sueli Mieko Oba-Shinjo
Summary: Tumor cell infiltrative ability in astrocytoma is strongly associated with extracellular matrix stiffness, and LOX family members play a role in collagen and elastin crosslinking. This study found that the expression levels of LOX family members increased with malignancy grade in astrocytoma, and correlated with matrisome gene expressions. The expression of the mechanosensitive transcription factor, beta-catenin, also increased with malignancy grade and was correlated with LOXL1 and LOXL3 expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Tao Jiang, Hao Xiao, Bin Li, Hangyuan He, Hui Wang, Liaobin Chen
Summary: In this study, the researchers investigated the mechanism by which prenatal dexamethasone exposure leads to low peak bone mass in female offspring. They found that dexamethasone exposure inhibited the development of fetal rat osteoclasts and caused hyperactivation of adult rat osteoclasts. Through further experiments, they determined that dexamethasone influenced the methylation and expression of lysyl oxidase in osteoclasts, leading to increased production of reactive oxygen species and reduced bone mass in offspring. This study provides insights into the programming effect of prenatal dexamethasone exposure on bone health.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Oncology
Bo Zhang, Chenglin Luo, Wenjin Xiao
Summary: This study showed that the LOX mutant LOXG473A may promote osteoclast formation by enhancing autophagy through the AMPK/mTOR pathway. The autophagy inhibitor 3-MA reduced osteoclast formation and resorption, while the autophagy agonist RAPA reversed these effects, suggesting that promoting autophagy can enhance the ability of LOXG473A to induce osteoclast formation.
ANNALS OF TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Chenyu Sun, Shaodi Ma, Yue Chen, Na Hyun Kim, Sujatha Kailas, Yichen Wang, Wenchao Gu, Yisheng Chen, John Pocholo W. Tuason, Chandur Bhan, Nikitha Manem, Yuting Huang, Ce Cheng, Zhen Zhou, Qin Zhou, Yanzhe Zhu
Summary: In liver cancer, all members of the LOX family exhibit significantly increased expression levels. LOXL2 has a high AUC of 0.946 and PPV of 0.994. LOX and LOXL3 are associated with worse prognosis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Xuanrong Chen, Yi Shao, Wanqing Wei, Haishan Shen, Yang Li, Yutong Chen, Qianwang Ma, Hanlin Li, Zhao Yang, Yuanjie Niu, Zhiqun Shang
Summary: The role of lysyl oxidase (LOX) in prostate cancer is controversial, but low LOX expression contributes to the progression of CRPC by upregulating IGFBP3. Restoring LOX expression may inhibit the progression of CRPC, suggesting LOX as a promising therapeutic target in PCa.
Article
Cell & Tissue Engineering
A. J. Ellingson, N. M. Pancheri, N. R. Schiele
Summary: This review focuses on the regulatory mechanisms of collagen crosslinking in tendons. Enzymatic crosslinking is mainly regulated by lysyl oxidase (LOX) and lysyl oxidase-like isoforms (LOXL), while non-enzymatic crosslinking is mediated by the formation of advanced glycation end products (AGEs). Factors that regulate the activity of LOX and LOXL enzymes include mechanical stimuli, cell signaling pathways, sex hormones, hypoxia, and interactions with intracellular or extracellular proteins. Accumulation of AGEs in tendons is associated with diabetic conditions and aging, and can be influenced by diet and mechanical stimuli. Understanding the regulation of enzymatic and non-enzymatic collagen crosslinking in tendons is crucial for tissue engineering and regenerative therapies aimed at restoring damaged tendon function.
EUROPEAN CELLS & MATERIALS
(2022)
Article
Oncology
Da Huang, Xiaohao Ruan, Jingyi Huang, Ning Zhang, Guangliang Jiang, Yi Gao, Danfeng Xu, Rong Na
Summary: Unmarried or urban patients were more likely to choose active surveillance/watchful waiting. The utilization and efficacy of conservative management were affected by socioeconomic factors, which might serve as a barrier of treatment decision-making and targeted a population in need of social support.
Article
Biochemistry & Molecular Biology
Wouter Bulten, Kimmo Kartasalo, Po-Hsuan Cameron Chen, Peter Strom, Hans Pinckaers, Kunal Nagpal, Yuannan Cai, David F. Steiner, Hester van Boven, Robert Vink, Christina Hulsbergen-van de Kaa, Jeroen van der Laak, Mahul B. Amin, Andrew J. Evans, Theodorus van der Kwast, Robert Allan, Peter A. Humphrey, Henrik Gronberg, Hemamali Samaratunga, Brett Delahunt, Toyonori Tsuzuki, Tomi Hakkinen, Lars Egevad, Maggie Demkin, Sohier Dane, Fraser Tan, Masi Valkonen, Greg S. Corrado, Lily Peng, Craig H. Mermel, Pekka Ruusuvuori, Geert Litjens, Martin Eklund
Summary: The PANDA challenge is the largest histopathology competition to date, aiming to catalyze the development of reproducible AI algorithms for Gleason grading in prostate cancer. The submitted algorithms achieved pathologist-level performance and their diversity and generalization were validated through cross-continental cohorts.
Article
Pathology
B. Delahunt, A. Steigler, C. Atkinson, D. Christie, G. Duchesne, L. Egevad, D. Joseph, D. N. Kenwright, J. Matthews, J. D. Murray, C. Oldmeadow, H. Samaratunga, N. A. Spry, M. C. Thunders, H. Hondermarck, J. W. Denham
Summary: Previous reports have shown that quantifying high tumour grade in prostate cancer patients is of prognostic significance. This study found that the length, percentage, and absolute values of Gleason pattern 4 (GP4) were significantly associated with distant progression of tumour, all-cause mortality, and cancer-specific mortality over a 10-year follow-up period. In addition, these parameters outperformed the division of cases according to Gleason score in terms of prognostic significance.
Article
Endocrinology & Metabolism
Claes Lindh, Hemamali Samaratunga, Brett Delahunt, Rebecka Bergstrom, Venkatesh Chellappa, John Yaxley, Johan Lindberg, Lars Egevad
Summary: Most ductal and acinar prostate adenocarcinoma components of mixed tumors share the same clonal origin. Ductal adenocarcinoma components often exhibit genome doubling events leading to aneuploidy, consistent with the aggressive nature of high grade prostate cancer.
Article
Radiology, Nuclear Medicine & Medical Imaging
Matthew J. Roberts, Andrew Morton, Nathan Papa, Anthony Franklin, Sheliyan Raveenthiran, William J. Yaxley, Geoffrey Coughlin, Troy Gianduzzo, Boon Kua, Louise McEwan, David Wong, Brett Delahunt, Lars Egevad, Hemamali Samaratunga, Nicholas Brown, Robert Parkinson, Louise Emmett, John W. Yaxley
Summary: PSMA intensity on PSMA PET/CT is a clinically significant biomarker for predicting oncological outcomes and biochemical recurrence-free survival in patients undergoing radical prostatectomy.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
Letter
Urology & Nephrology
Hemamali Samaratunga, Brett Delahunt, Lars Egevad
Article
Urology & Nephrology
S. Raveenthiran, W. J. Yaxley, T. Franklin, G. Coughlin, M. Roberts, T. Gianduzzo, B. Kua, H. Samaratunga, B. Delahunt, L. Egevad, D. Wong, L. McEwan, N. Brown, R. Parkinson, R. Esler, J. W. Yaxley
Summary: The study aimed to evaluate the ability of mpMRI and PSMA PET/CT individually and in combination to predict tumor location and Gleason score in prostate cancer. The results showed that combining PSMA PET/CT with mpMRI can improve the detection of significant prostate cancer.
JOURNAL OF UROLOGY
(2022)
Letter
Pathology
Hemamal Samaratunga, Tony Gianduzzo, Joanna Perry-Keene, Lars Egevad, Brett Delahunt
Article
Cell Biology
Lars Egevad, Brett Delahunt, Kenneth A. Iczkowski, Theo van der Kwast, Geert J. L. H. van Leenders, Katia R. M. Leite, Chin-Chen Pan, Hemamali Samaratunga, Toyonori Tsuzuki, Nita Mulliqi, Xiaoyi Ji, Henrik Olsson, Masi Valkonen, Pekka Ruusuvuori, Martin Eklund, Kimmo Kartasalo
Summary: There is evidence that cribriform morphology is associated with a worse prognosis for prostatic adenocarcinoma. This study aimed to investigate the reproducibility of cribriform cancer diagnosis in prostate needle biopsies. A panel of nine prostate pathology experts independently reviewed 304 digitised biopsies and achieved a 2/3 consensus diagnosis of cribriform and noncribriform cancer in 90% of the cases. Strict diagnostic criteria were used to identify cribriform patterns and generate a set of consensus cases for standardization.
Article
Multidisciplinary Sciences
Henrik Olsson, Kimmo Kartasalo, Nita Mulliqi, Marco Capuccini, Pekka Ruusuvuori, Hemamali Samaratunga, Brett Delahunt, Cecilia Lindskog, Emiel A. M. Janssen, Anders Blilie, Lars Egevad, Ola Spjuth, Martin Eklund
Summary: This study demonstrates the use of conformal prediction to detect unreliable predictions in the context of prostate biopsy diagnosis and grading. The results show that conformal prediction can improve the accuracy of AI systems and detect systematic differences in external data, highlighting unreliable predictions.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, General & Internal
M. Alvaro Berbis, David S. McClintock, Andrey Bychkov, Jeroen Van der Laak, Liron Pantanowitz, Jochen K. Lennerz, Jerome Y. Cheng, Brett Delahunt, Lars Egevad, Catarina Eloy, Alton B. Farris III, Filippo Fraggetta, Raimundo Garcia del Moral, Douglas J. Hartman, Markus D. Herrmann, Eva Hollemans, Kenneth A. Iczkowski, Aly Karsan, Mark Kriegsmann, Mohamed E. Salama, John H. Sinard, J. Mark Tuthill, Bethany Williams, Cesar Casado-Sanchez, Victor Sanchez-Turrion, Antonio Luna, Jose Aneiros-Fernandez, Jeanne Shen
Summary: AI is expected to be routinely and impactfully used in pathology practice by 2030, according to experts in the field. This consensus study highlights the anticipated short-to-mid-term impact of AI and raises important practical, ethical, and legal challenges that need to be addressed prior to its clinical implementation.
Article
Oncology
Naveen S. Vasudev, Ghislaine Scelo, Kate I. Glennon, Michelle Wilson, Louis Letourneau, Robert Eveleigh, Nazanin Nourbehesht, Madeleine Arseneault, Antoine Paccard, Lars Egevad, Juris Viksna, Edgars Celms, Sharon M. Jackson, Behnoush Abedi-Ardekani, Anne Y. Warren, Peter J. Selby, Sebastian Trainor, Michael Kimuli, Jon Cartledge, Naeem Soomro, Adebanji Adeyoju, Poulam M. Patel, Magdalena B. Wozniak, Ivana Holcatova, Antonin Brisuda, Vladimir Janout, Estelle Chanudet, David Zaridze, Anush Moukeria, Oxana Shangina, Lenka Foretova, Marie Navratilova, Dana Mates, Viorel Jinga, Ljiljana Bogdanovic, Bozidar Kovacevic, Anne Cambon-Thomsen, Guillaume Bourque, Alvis Brazma, Jorg Tost, Paul Brennan, Mark Lathrop, Yasser Riazalhosseini, Rosamonde E. Banks
Summary: Targeted gene sequencing can help in risk prediction and adjuvant treatment decisions for patients with resected localized ccRCC. Mutations in the VHL gene have a significant impact on patient outcomes, independent of other gene mutations. Genomic characterization can personalize treatment discussions and inform future adjuvant trial design.
CLINICAL CANCER RESEARCH
(2023)
Editorial Material
Pathology
Murali Varma, Brett Delahunt, Liang Cheng, Runjan Chetty, Eva Comperat, Vikram Deshpande, Lars Egevad, Theodorus H. van der Kwast, Antonio Lopez-Beltran, W. Glenn McCluggage
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Letter
Pathology
Hemamali Samaratunga, Lars Egevad, Brett Delahunt
Review
Pathology
Murali Varma, Laura C. Collins, Runjan Chetty, Dipti M. Karamchandani, Karen Talia, John Dormer, Monika Vyas, Brendan Conn, Yaileen D. Guzman-Arocho, Adam Jones, Miranda Pring, W. Glenn Mccluggage
Summary: This paper highlights the importance of macroscopic examination and tissue sampling in histopathology reporting and discusses potential solutions and challenges. It emphasizes the need for adequate guidance and supervision in macroscopic examination and highlights the importance of clinical context, specimen fixation, macroscopic descriptions, and tissue sampling.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Urology & Nephrology
Johan Wanman, Kasim Abul-Kasim, Julius Semenas, Elin Thysell, Anders Bergh, Pernilla Wikstrom, Sead Crnalic
Summary: This study explores the presence and prognostic value of myeloma-like prostate cancer bone metastases and its relation to clinical, molecular, and morphological prognostic markers. The myeloma-like metastatic pattern is associated with poor survival and neurological outcomes after surgery for metastatic spinal cord compression.
EUROPEAN UROLOGY OPEN SCIENCE
(2023)
