Article
Cell Biology
Melis Asal, Gamze Kocak, Vedat Sari, Tuba Recber, Emirhan Nemutlu, Canan Asli Utine, Sinan Guven
Summary: The lacrimal gland is essential for maintaining the health and function of the eye's surface. Through the use of induced pluripotent stem cells, researchers have successfully generated functional lacrimal gland organoids in vitro. These organoids exhibit the characteristics of lacrimal gland development and are capable of secreting tear proteins. The study also identified the role of miR-205 in regulating the development of the organoids. This research has significant implications for improving treatment options for lacrimal gland dysfunction and further understanding human lacrimal gland development and morphogenesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Medicine, Research & Experimental
Xiaotong Lin, Yao Sun, Xin Dong, Zishen Liu, Ryohichi Sugimura, Guozhu Xie
Summary: Adoptive cell therapies (ACT) using CAR-modified immune cells, particularly CAR-NK cells, have gained attention for their potential in cancer treatment. The use of iPSC-derived NK cells to produce CAR-iNK cells provides a standardized and scalable product for cancer immunotherapy. This review discusses the manufacturing techniques, genetic modification strategies, and preclinical and clinical evidence for CAR-iNK cells, as well as the challenges and prospects of this novel cellular immunotherapy in cancer treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Biochemistry & Molecular Biology
Demitria M. Vasilatis, Christopher A. Lucchesi, Paramita M. Ghosh
Summary: Dogs naturally develop prostate cancer similar to aggressive forms found in humans. Prostate cancer samples in dogs often lack androgen receptor (AR), which can enhance our understanding of AR-indifferent prostate cancer in humans. This review highlights the molecular similarities between dog and human prostate cancer variants, suggesting the potential use of dogs as pre-clinical animal models for developing new therapies and diagnostics that can benefit both species.
Editorial Material
Cell Biology
Li Xin
Summary: EZH2 has been shown to promote the development of castration-resistant prostate cancer (CRPC) by interacting with the androgen receptor (AR) to reprogram its transcriptional activity, facilitating the transition of CRPC into a lineage infidelity state.
NATURE CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Haozhe Zhang, Yi Zhou, Zengzhen Xing, Rajiv Kumar Sah, Junqi Hu, Hailiang Hu
Summary: This review discusses the close relationship between the evolution of prostate cancer and androgen levels and the status of the androgen receptor. It also explores how alterations in androgen metabolism contribute to the resistance to anti-androgen therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Jiaqian Liang, Liyang Wang, Larysa Poluben, Mannan Nouri, Seiji Arai, Lisha Xie, Olga S. Voznesensky, Laura Cato, Xin Yuan, Joshua W. Russo, Henry W. Long, Myles Brown, Shaoyong Chen, Steven P. Balk
Summary: In castration-resistant prostate cancer (CRPC), the splice variant ARv7 can function independently of the full length ARfl, with both contributing independently to overall AR activity.
Article
Biochemical Research Methods
Ann Zeleniak, Connor Wiegand, Wen Liu, Catherine McCormick, K. Ravikumar, Amir Alavi, Haonan Guan, Suzanne Bertera, Robert Lakomy, Asako Tajima, Henry Cohen, Stephanie Wong, Lame Balikani, Benjamin Mizerak, Ziv Bar-Joseph, Massimo Trucco, Ipsita Banerjee, Yong Fan
Summary: This study successfully engineered human thymus organoids that can support the de novo generation of functional human T cells, exhibiting cellular and humoral immune functions in mice. This finding could enhance the efficiency of studying T cell-mediated immune disorders and drug discovery.
Article
Oncology
Emuejevoke Olokpa, Sammed N. Mandape, Siddharth Pratap, La Monica Stewart
Summary: The study used RNA sequencing to identify the signaling pathways regulated by metformin in androgen-receptor positive, castration-resistant prostate cancer cells. Metformin was found to alter the expression of genes involved in metabolic pathways, the spliceosome, RNA transport, and protein processing within the endoplasmic reticulum, as well as in ErbB, insulin, mTOR, TGF-beta, MAPK, and Wnt signaling pathways. Some of the metformin-regulated genes are known to be direct transcriptional targets of p53 or AR, and metformin-induced reductions in AR mRNA and protein levels contributed to these alterations in gene expression.
Article
Cell Biology
Annelies Van Hemelryk, Ingrid Tomljanovic, Corrina M. A. de Ridder, Debra C. Stuurman, Wilma J. Teubel, Sigrun Erkens-Schulze, Esther Verhoef, Sebastiaan Remmers, Amrish J. Mahes, Geert J. L. H. van Leenders, Martin E. van Royen, Harmen J. G. van de Werken, Magda Grudniewska, Guido W. Jenster, Wytske M. van Weerden
Summary: This study presents patient-derived xenografts (PDXs) and matching PDX-derived organoids (PDXOs) as new models for studying castration-resistant prostate cancer (CRPC). These models accurately reflect donor tumors and can predict patient responses to different treatments. The study provides valuable insights into the genomic and transcriptomic features of CRPC and offers a resource for studying treatment-induced resistance mechanisms.
Article
Biochemistry & Molecular Biology
Waqas Azeem, Jan Roger Olsen, Margrete Reime Hellem, Yaping Hua, Kristo Marvyin, Xisong Ke, Anne Margrete oyan, Karl-Henning Kalland
Summary: This study investigated the role of GATA2 in prostate epithelial cells and found that exogenous GATA2 protein was rapidly degraded and its expression could be rescued by proteasome inhibitors. The inhibition of proteasome also induced the transcription of AR mRNA and luminal marker genes in prostate cells. Different intrinsic mechanisms restricted the expression of GATA2 in these cells. These findings suggest the existence of crucial cofactors for AR mRNA expression and luminal differentiation at the proteolytic level.
Article
Multidisciplinary Sciences
Marzia Di Donato, Carmine Ostacolo, Pia Giovannelli, Veronica Di Sarno, Isabel M. Gomez Monterrey, Pietro Campiglia, Antimo Migliaccio, Alessia Bertamino, Gabriella Castoria
Summary: TRPM8 antagonists can inhibit androgen-dependent prostate cancer cell proliferation, migration, and invasiveness, and have a significant reverse effect on the spheroid size increase induced by androgens in prostate cancer cells. Selected antagonists interfere with non-genomic androgen action, disrupt the androgen-induced androgen receptor/TRPM8 complex assembly, and prevent the increase in intracellular calcium levels in prostate cancer cells.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Tuyen Thanh Tran, Keesook Lee
Summary: The study revealed that overexpression of JAG1's intracellular domain JICD in prostate cancer cells increased AR-Vs expression, enhanced AR activity in both androgen-independent and dependent conditions, raised the levels of the PCSC marker CD133, and altered components in PCSC-related signaling pathways. This suggests a critical role of JICD in promoting androgen independence and stem-like properties in PC cells.
Review
Biochemistry & Molecular Biology
Margherita Corti, Stefano Lorenzetti, Alessandro Ubaldi, Romano Zilli, Daniele Marcoccia
Summary: The role of endocrine disruptors in the human prostate gland is overlooked, but they can influence the homeostasis and diseases of the prostate, including prostate cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell & Tissue Engineering
Ana C. Silva, Oriane B. Matthys, David A. Joy, Mara A. Kauss, Vaishaali Natarajan, Michael H. Lai, Diwaker Turaga, Andrew P. Blair, Michael Alexanian, Benoit G. Bruneau, Todd C. McDevitt
Summary: This study demonstrates the successful generation of a human multilineage iPSC-derived organoid model that recapitulates cooperative cardiac and gut development, showing the importance of endoderm tissue in driving cardiac tissue features. This advancement allows for further examination of multi-tissue interactions during development, physiological maturation, and disease.
Article
Oncology
Ruopeng Su, Lei Chen, Zhou Jiang, Minghao Yu, Weiwei Zhang, Zehua Ma, Yiyi Ji, Kai Shen, Zhixiang Xin, Jun Qi, Wei Xue, Qi Wang
Summary: In this study, the researchers investigated the status of androgen receptor (AR) in prostate cancer with neuroendocrine differentiation. They found the existence of AR(HIGH)/NEHIGH prostate cancer and observed a correlation between AR loss tumors and adverse clinical stages. The researchers also observed the co-localization of AR and NE markers in prostate cancer cells using immunofluorescence staining. This study provides new insights into the cellular plasticity of prostate cancer with neuroendocrine differentiation and has implications for therapeutic development.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Roshan A. Karunamuni, Minh-Phuong Huynh-Le, Chun C. Fan, Wesley Thompson, Rosalind A. Eeles, Zsofia Kote-Jarai, Kenneth Muir, Artitaya Lophatananon, Catherine M. Tangen, Phyllis J. Goodman, Ian M. Thompson, William J. Blot, Wei Zheng, Adam S. Kibel, Bettina F. Drake, Olivier Cussenot, Geraldine Cancel-Tassin, Florence Menegaux, Therese Truong, Jong Y. Park, Hui-Yi Lin, Jeannette T. Bensen, Elizabeth T. H. Fontham, James L. Mohler, Jack A. Taylor, Luc Multigner, Pascal Blanchet, Laurent Brureau, Marc Romana, Robin J. Leach, Esther M. John, Jay Fowke, William S. Bush, Melinda Aldrich, Dana C. Crawford, Shiv Srivastava, Jennifer C. Cullen, Gyorgy Petrovics, Marie-Elise Parent, Jennifer J. Hu, Maureen Sanderson, Ian G. Mills, Ole A. Andreassen, Anders M. Dale, Tyler M. Seibert
Summary: The study identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry, bringing the performance levels to those comparable to Europeans.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Review
Oncology
Harri M. Itkonen, Massimo Loda, Ian G. Mills
Summary: OGT enzyme is involved in the posttranslational modification of serine and threonine residues, and its increased expression is a common feature in most human cancers. Inhibition of OGT reduces cancer cell proliferation by affecting known regulators of cancer cell proliferation. While OGT has potential in cancer therapy, further understanding of its substrate specificity and development of more specific inhibitors are needed.
MOLECULAR CANCER RESEARCH
(2021)
Article
Oncology
Roshan A. Karunamuni, Minh-Phuong Huynh-Le, Chun C. Fan, Wesley Thompson, Rosalind A. Eeles, Zsofia Kote-Jarai, Kenneth Muir, Artitaya Lophatananon, Johanna Schleutker, Nora Pashayan, Jyotsna Batra, Henrik Groenberg, Eleanor I. Walsh, Emma L. Turner, Athene Lane, Richard M. Martin, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Borge G. Nordestgaard, Catherine M. Tangen, Robert J. MacInnis, Alicja Wolk, Demetrius Albanes, Christopher A. Haiman, Ruth C. Travis, Janet L. Stanford, Lorelei A. Mucci, Catharine M. L. West, Sune F. Nielsen, Adam S. Kibel, Fredrik Wiklund, Olivier Cussenot, Sonja I. Berndt, Stella Koutros, Karina Dalsgaard Sorensen, Cezary Cybulski, Eli Marie Grindedal, Jong Y. Park, Sue A. Ingles, Christiane Maier, Robert J. Hamilton, Barry S. Rosenstein, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Manuel R. Teixeira, Hermann Brenner, Esther M. John, Radka Kaneva, Christopher J. Logothetis, Susan L. Neuhausen, Azad Razack, Lisa F. Newcomb, Marija Gamulin, Nawaid Usmani, Frank Claessens, Manuela Gago-Dominguez, Paul A. Townsend, Monique J. Roobol, Wei Zheng, Ian G. Mills, Ole A. Andreassen, Anders M. Dale, Tyler M. Seibert
Summary: In this study, we found that incorporating an additional 120 SNPs (PHS166 vs PHS46) significantly improved hazard ratios for prostate cancer, while the positive predictive value of PSA testing remained the same.
PROSTATE CANCER AND PROSTATIC DISEASES
(2021)
Article
Oncology
Margaret M. Centenera, Julia S. Scott, Jelle Machiels, Zeyad D. Nassar, Deanna C. Miller, Irene Zinonos, Jonas Dehairs, Ingrid J. G. Burvenich, Giorgia Zadra, Paolo M. Chetta, Clyde Bango, Emma Evergren, Natalie K. Ryan, Joanna L. Gillis, Chui Yan Mah, Terence Tieu, Adrienne R. Hanson, Ryan Carelli, Katarzyna Bloch, Vasilios Panagopoulos, Etienne Waelkens, Rita Derua, Elizabeth D. Williams, Andreas Evdokiou, Anna Cifuentes-Rius, Nicolas H. Voelcker, Ian G. Mills, Wayne D. Tilley, Andrew M. Scott, Massimo Loda, Luke A. Selth, Johannes Swinnen, Lisa M. Butler
Summary: This study identifies phospholipid elongation as a new metabolic target of androgen action that is critical for prostate tumor metastasis.
Article
Multidisciplinary Sciences
Minh-Phuong Huynh-Le, Chun Chieh Fan, Roshan Karunamuni, Wesley K. Thompson, Maria Elena Martinez, Rosalind A. Eeles, Zsofia Kote-Jarai, Kenneth Muir, Johanna Schleutker, Nora Pashayan, Jyotsna Batra, Henrik Gronberg, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Sune F. Nielsen, Borge G. Nordestgaard, Fredrik Wiklund, Catherine M. Tangen, Graham G. Giles, Alicja Wolk, Demetrius Albanes, Ruth C. Travis, William J. Blot, Wei Zheng, Maureen Sanderson, Janet L. Stanford, Lorelei A. Mucci, Catharine M. L. West, Adam S. Kibel, Olivier Cussenot, Sonja I. Berndt, Stella Koutros, Karina Dalsgaard Sorensen, Cezary Cybulski, Eli Marie Grindedal, Florence Menegaux, Kay-Tee Khaw, Jong Y. Park, Sue A. Ingles, Christiane Maier, Robert J. Hamilton, Stephen N. Thibodeau, Barry S. Rosenstein, Yong-Jie Lu, Stephen Watya, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Chad Huff, Manuel R. Teixeira, Luc Multigner, Robin J. Leach, Lisa Cannon-Albright, Hermann Brenner, Esther M. John, Radka Kaneva, Christopher J. Logothetis, Susan L. Neuhausen, Kim De Ruyck, Hardev Pandha, Azad Razack, Lisa F. Newcomb, Jay H. Fowke, Marija Gamulin, Nawaid Usmani, Frank Claessens, Manuela Gago-Dominguez, Paul A. Townsend, William S. Bush, Monique J. Roobol, Marie-Elise Parent, Jennifer J. Hu, Ian G. Mills, Ole A. Andreassen, Anders M. Dale, Tyler M. Seibert
Summary: The study found that a polygenic hazard score can risk-stratify men for prostate cancer in a multi-ethnic dataset, with significant and effective associations observed across different genetic ancestries.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Francesca Amoroso, Kimberley Glass, Reema Singh, Francisco Liberal, Rebecca E. Steele, Sarah Maguire, Rohinton Tarapore, Joshua E. Allen, Sandra Van Schaeybroeck, Karl T. Butterworth, Kevin Prise, Joe M. O'Sullivan, Suneil Jain, David J. Waugh, Ian G. Mills
Summary: The study demonstrated that ONC201 can enhance the radiation response of prostate cancer cells by suppressing the expression of cell cycle and DNA repair factors.
SCIENTIFIC REPORTS
(2021)
Review
Oncology
Dimitrios Doultsinos, Ian G. Mills
Summary: Prostate cancer poses a significant public health burden globally with advancements in treatment mainly targeting the androgen receptor to improve patient outlook. Molecular signatures serve as maps of tumor evolution potential and aid in predicting aggressive disease development in patients.
Article
Oncology
Rafael S. Martinez, Mark J. Salji, Linda Rushworth, Chara Ntala, Giovanny Rodriguez Blanco, Ann Hedley, William Clark, Paul Peixoto, Eric Hervouet, Elodie Renaude, Sonia H. Y. Kung, Laura C. A. Galbraith, Colin Nixon, Sergio Lilla, Gillian M. Mackay, Ladan Fazli, Luke Gaughan, David Sumpton, Martin E. Gleave, Sara Zanivan, Arnaud Blomme, Hing Y. Leung
Summary: This study identified SLFN5 as a novel regulator of the LAT1 amino acid transporter in castration-resistant prostate cancer (CRPC), contributing to mTORC1 activity. High expression of SLFN5 in CRPC tumors was correlated with poor patient outcome, indicating its clinical relevance as a potential target for CRPC treatment.
Article
Oncology
Pamela J. Maxwell, Melanie McKechnie, Christopher W. Armstrong, Judith M. Manley, Chee Wee Ong, Jenny Worthington, Ian G. Mills, Daniel B. Longley, James P. Quigley, Amina Zoubeidi, Johann S. de Bono, Elena Deryugina, Melissa J. LaBonte, David J. J. Waugh
Summary: Inhibiting androgen signaling using androgen signaling inhibitors is the primary treatment for castrate-resistant prostate cancer. However, acquired resistance to androgen receptor-targeted therapy is a major challenge. This study found that enzalutamide induces hypoxia and angiogenesis, which may contribute to relapse. Concurrent inhibition of two hypoxia-induced factors can prolong tumor sensitivity to enzalutamide.
MOLECULAR CANCER RESEARCH
(2022)
Article
Oncology
Mamatha Kakarla, Sathyavathi ChallaSivaKanaka, Mary F. Dufficy, Victoria Gil, Yana Filipovich, Renee Vickman, Susan E. Crawford, Simon W. Hayward, Omar E. Franco
Summary: The increase of EFNB ligands in CAF in the TME of PCa plays a crucial role in promoting tumor growth and modulating the tumor environment. Activation of EFNB by Src family kinases transforms normal fibroblasts into CAF that affect PCa progression by secreting factors that enhance tumor growth and invasion. Through stromal-epithelial interactions, CAF contribute significantly to the tumorigenicity of PCa cells.
Article
Oncology
Maria Georgiou, Chunbo Yang, Robert Atkinson, Kuan-Ting Pan, Adriana Buskin, Marina Moya Molina, Joseph Collin, Jumana Al-Aama, Franziska Goertler, Sebastian E. J. Ludwig, Tracey Davey, Reinhard Luhrmann, Sushma Nagaraja-Grellscheid, Colin A. Johnson, Robin Ali, Lyle Armstrong, Viktor Korolchuk, Henning Urlaub, Sina Mozaffari-Jovin, Majlinda Lako
Summary: Mutations in PRPF31, a core protein of the spliceosomal tri-snRNP complex, cause autosomal-dominant retinitis pigmentosa (adRP). This study used iPSC technology to generate retinal organoids and RPE models from PRPF31-adRP patients, and found that RNA splicing, autophagy and lysosome, and visual cycle pathways were significantly affected. The accumulation of cytoplasmic aggregates and impaired waste disposal mechanisms were also observed in patient-derived cells. Activation of the autophagy pathway reduced the aggregates and improved cell survival.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Grace Kennedy, Olivia Gibson, Daire T. O'Hare, Ian G. Mills, Emma Evergren
Summary: Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a serine/threonine protein kinase involved in regulating energy homeostasis and cell growth. Its deregulation has implications in metabolic diseases and cancer. Recent research has explored new functions of CaMKK2, such as lipogenesis and Golgi vesicle trafficking. This review discusses the role of CaMKK2 in membrane trafficking mechanisms and its implications for disease.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Developmental Biology
Parmveer Singh, Nadia A. Lanman, Hannah L. R. Kendall, Laura Wilson, Ryan Long, Omar E. Franco, Adriana Buskin, Colin G. Miles, Simon W. Hayward, Rakesh Heer, Craig N. Robson
Summary: The reactivation of developmental genes and pathways during adulthood may contribute to the pathogenesis of diseases such as prostate cancer. Studying the mechanistic links between development and disease can help identify signaling pathways leading to prostate disease. However, more characterization of the mechanisms underlying prostate development is needed to fully understand the connection between development and disease.
Review
Biochemistry & Molecular Biology
Adriana Buskin, Emma Scott, Ryan Nelson, Luke Gaughan, Craig N. Robson, Rakesh Heer, Anastasia C. Hepburn
Summary: A key challenge in the management of prostate cancer is its heterogeneity, and there is an urgent need for models that can reflect clinical diversity and resistant phenotypes. The three-dimensional organoid model has revolutionized cancer research, providing opportunities for disease modeling, drug screening, and precision medicine. However, there are limitations in emulating the tumor microenvironment and metastasis process, as well as the epigenome profile, which need to be addressed to maximize the translational relevance of organoids.
Article
Biochemistry & Molecular Biology
Srinivasa R. Rao, Andrew Protheroe, Lucia Cerundolo, David Maldonado-Perez, Lisa Browning, Alastair D. Lamb, Richard J. Bryant, Ian G. Mills, Dan J. Woodcock, Freddie C. Hamdy, Ian P. M. Tomlinson, Clare Verrill
Summary: Prostate cancer can present in different types, including acinar adenocarcinoma, neuroendocrine, and ductal carcinoma, which are associated with aggressive disease. By sequencing archival tissue, two cases were studied, revealing a common ancestry between small-cell neuroendocrine and ductal prostatic carcinoma. A patient with treatment-related neuroendocrine prostate carcinoma also showed genetic alterations associated with poor prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
