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.
Review
Cell Biology
Vincenza Conteduca, Alessandra Mosca, Nicole Brighi, Ugo de Giorgi, Pasquale Rescigno
Summary: Prostate cancer is a common cancer in men and patients may develop metastatic disease after radical treatments. Prognostic biomarkers are urgently needed to define patients' risk of cancer-related death.
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.
Review
Endocrinology & Metabolism
Anna E. Harris, Veronika M. Metzler, Jennifer Lothion-Roy, Dhruvika Varun, Corinne L. Woodcock, Daisy B. Haigh, Chantelle Endeley, Maria Haque, Michael S. Toss, Mansour Alsaleem, Jenny L. Persson, Lorraine J. Gudas, Emad Rakha, Brian D. Robinson, Francesca Khani, Laura M. Martin, Jenna E. Moyer, Juliette Brownlie, Srinivasan Madhusudan, Cinzia Allegrucci, Victoria H. James, Catrin S. Rutland, Rupert G. Fray, Atara Ntekim, Simone de Brot, Nigel P. Mongan, Jennie N. Jeyapalan
Summary: This article summarizes the current status of anti-androgen clinical trials, discusses the potential of novel combination therapies, and explores recent advances in the development of novel epigenetic targeted therapies that may prevent or reverse disease progression in patients with advanced prostate cancer.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
David Ka-Wai Leung, Peter Ka-Fung Chiu, Chi-Fai Ng, Jeremy Yuen-Chun Teoh
Summary: The management of castration-resistant prostate cancer has seen significant progress, with three novel hormonal agents showing survival benefits in non-metastatic patients and a wider range of management options being investigated for metastatic disease.
Article
Medicine, Research & Experimental
Sue Jin Moon, Byong Chang Jeong, Hwa Jin Kim, Joung Eun Lim, Hye-Jeong Kim, Ghee Young Kwon, Joshua A. Jackman, Jeong Hoon Kim
Summary: The study identified BCT as a potent inhibitor targeting both AR-FL and AR-V7 activities in CRPC, effectively suppressing tumor growth and metastasis. Mechanistically, BCT disrupts the interaction of HSP90 with AR-FL/AR-V7, leading to their degradation and showing promising therapeutic potential against CRPC.
Article
Oncology
Xiaolei Shi, Abderrahman Day, Hannah E. Bergom, Sydney Tape, Sylvan C. Baca, Zoi E. Sychev, Gabrianne Larson, Asha Bozicevich, Justin M. Drake, Nicholas Zorko, Jinhua Wang, Charles J. Ryan, Emmanuel S. Antonarakis, Justin Hwang
Summary: The study identifies B7-H3 as an immune checkpoint overexpressed in prostate cancer, particularly in metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide-resistant mCRPC cells show increased expression of B7-H3, and it is associated with resistance signaling pathways. The gene network of B7-H3 is strongly correlated with androgen receptor (AR) and its co-factors, suggesting potential therapeutic targets for mCRPC.
NPJ PRECISION ONCOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Thi Khanh Le, Chaima Cherif, Kenneth Omabe, Clement Paris, Francois Lannes, Stephane Audebert, Emilie Baudelet, Mourad Hamimed, Dominique Barbolosi, Pascal Finetti, Cyrille Bastide, Ladan Fazli, Martin Gleave, Francois Bertucci, David Taieb, Palma Rocchi
Summary: The heat shock protein 27 (Hsp27) plays a crucial role in the progression of castration-resistant prostate cancer (CRPC), and an antisense oligonucleotide (ASO) against Hsp27 has been evaluated in clinical trials. This study demonstrates that Hsp27 regulates the expression of the human DEAD-box protein 5 (DDX5) and identifies DDX5 as a potential therapeutic target for CRPC treatment.
Article
Cell & Tissue Engineering
Yalan Xu, Jie Mu, Zhixia Zhou, Yu Leng, Yali Yu, Xiuyue Song, Aihua Liu, Hai Zhu, Jing Li, Dong Wang
Summary: The study isolated and cultured a novel type of castration-resistant intermediate prostate stem cells that can rapidly proliferate in 2D culture dishes and be maintained for over six months. These stem cells express markers of both basal and luminal cells, and can differentiate into prostate organoids and tissues.
STEM CELL RESEARCH & THERAPY
(2022)
Review
Oncology
Masaki Shiota, Satoshi Endo, Leandro Blas, Naohiro Fujimoto, Masatoshi Eto
Summary: Castration resistance is caused by the abnormal activation of androgen receptor (AR) signaling through intracrine activation of androgen precursors from adrenal glands. To address this, novel AR pathway inhibitors (ARPIs) have been developed to suppress androgen synthesis or AR activation. However, resistance to these ARPIs can occur due to the persistent androgen environment despite intensive AR signaling suppression.
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
(2023)
Review
Biochemistry & Molecular Biology
Ivan Henriquez, Mack I. I. I. I. I. I. Roach, Todd M. Morgan, Alberto Bossi, Junior A. Gomez, Oscar Abuchaibe, Felipe Counago
Summary: mCRPC is a complex disease with a wide range of molecular tumor behavior and high risk of progression, making early detection and treatment crucial. Treatment options have improved significantly in recent years, but clinicians find it challenging to keep up with the rapidly changing therapeutic landscape.
Review
Oncology
Thi Khanh Le, Quang Hieu Duong, Virginie Baylot, Christelle Fargette, Michael Baboudjian, Laurence Colleaux, David Taieb, Palma Rocchi
Summary: Castration-resistant prostate cancer remains a significant medical challenge, and it is important to understand the underlying mechanisms of resistance and develop new treatment approaches. This review provides an overview of the mechanisms contributing to CRPC progression and discusses current treatment options.
Article
Medicine, General & Internal
Daniele Bianchi, Cristina Falcinelli, Leonardo Molinari, Alessio Gizzi, Alberto Di Martino
Summary: Metastatic lesions in vertebrae can compromise mechanical integrity and increase fracture risk. A computational approach assessing the effect of lesion size, location, type, and shape on fracture load and patterns is critical for predicting overall mechanical response. Size, location, and type of metastasis significantly affect vertebral mechanical response, showing the importance of considering these parameters in estimating fracture risk.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cell Biology
Xiao Li, Fei Li, Fei Ye, Haotian Guo, Wentao Chen, Jia Jin, Yiran Wang, Pengfei Dai, Huili Shi, Hongru Tao, Wenzhen Dang, Yiluan Ding, Mingchen Wang, Hualiang Jiang, Kaixian Chen, Naixia Zhang, Dong Gao, Yuanyuan Zhang, Cheng Luo
Summary: In castration-resistant prostate cancer (CRPC), the limited response to androgen receptor (AR) antagonists is mainly attributed to the expression of AR-variants and restored AR signaling. We demonstrate that the metabolite spermine inhibits AR-FL and AR-V7 signaling and suppresses CRPC cell proliferation by directly binding and inhibiting PRMT1. Additionally, spermine supplementation restrains CRPC growth in vivo. Thus, spermine and PRMT1 inhibition may be powerful strategies for overcoming the limitations of current AR-based therapies in CRPC.
Article
Oncology
Maryam Labaf, Muqing Li, Lily Ting, Breelyn Karno, Songqi Zhang, Shuai Gao, Susan Patalano, Jill A. A. Macoska, Kourosh Zarringhalam, Dong Han, Changmeng Cai
Summary: This study examines the acute effects of overexpressed androgen receptor (AR) on its cistrome and transcriptome in a prostate cancer (PCa) model. The results show that overexpression of AR leads to redistribution of AR chromatin binding and activation of a distinct transcription program, including DNA damage repair pathways. The study also predicts the involvement of EZH2 in this AR reprogramming and identifies a subset of AR/EZH2 co-targeting genes that are overexpressed in castration-resistant PCa and associated with worse patient outcomes.
FRONTIERS IN ONCOLOGY
(2022)
Article
Endocrinology & Metabolism
M. Revel, F. Bermond, F. Duboeuf, D. Mitton, H. Follet
Summary: Although HR-pQCT allows for assessment of bone microstructure and strength to evaluate fracture risk, it does not show clear improvement in accuracy compared to DXA measurements. Changes in loading conditions do not enhance the prediction of radius fracture risk based on ex vivo experiments, as demonstrated by similar ROC curves and accuracies with different loading conditions.
Article
Gastroenterology & Hepatology
Regis Souche, Guillaume Tosato, Benjamin Riviere, Jean-Christophe Valats, Antoine Debourdeau, Nicolas Flori, Didier Pourquier, Jean-Michel Fabre, Eric Assenat, Jacques Colinge, Andrei Turtoi
Summary: Protein signature for PDAC screening with high sensitivity and specificity was discovered using protein extracts from EUS-FNA liquid. The combination of PSS and patient age achieved 100% certainty in identifying PDAC patients. The study also showed that PSS accurately identified inconclusive EUS-FNA biopsies.
Article
Cell Biology
Isabelle K. Vila, Hanane Chamma, Alizee Steer, Mathilde Saccas, Clara Taffoni, Evgenia Turtoi, Line S. Reinert, Saqib Hussain, Johanna Marines, Lei Jin, Xavier Bonnefont, Mathieu Hubert, Olivier Schwartz, Soren R. Paludan, Gaetan Van Simaeys, Gilles Doumont, Bijan Sobhian, Dimitrios Vlachakis, Andrei Turtoi, Nadine Laguette
Summary: The coordinated alteration of immune and metabolic homeostasis plays a crucial role in inflammation-related pathologies. In this study, the researchers discovered a negative regulatory feedback loop between the STING protein and the FADS2 enzyme, which fine-tunes inflammatory responses. The findings highlight the importance of metabolic alterations in human pathologies associated with abnormal STING activation.
Article
Biochemistry & Molecular Biology
Barbara Chiavarina, Roberto Ronca, Yukihiro Otaka, Roger Bryan Sutton, Sara Rezzola, Takehiko Yokobori, Paola Chiodelli, Regis Souche, Didier Pourquier, Antonio Maraver, Gavino Faa, Lakhdar Khellaf, Evgenia Turtoi, Tetsunari Oyama, Stephanie Gofflot, Akeila Bellahcene, Olivier Detry, Philippe Delvenne, Vincent Castronovo, Masahiko Nishiyama, Andrei Turtoi
Summary: Cancer-associated fibroblasts (CAF) play important roles in tumor microenvironment and tumorigenesis. In hepatocellular carcinoma (HCC), there are three major CAF populations, one of which expresses prolargin protein. Prolargin acts as an angiogenesis modulator and tumor suppressor in HCC, inhibiting the activity of pro-angiogenic proteins. Stabilizing prolargin levels in the CAF_Port subpopulation may reverse their tumor-antagonizing properties.
Article
Cell Biology
Sophie Pattingre, Andrei Turtoi
Summary: The BCL-2-associated athanogene (BAG) family is a group of multifunctional co-chaperones that play important roles in cellular quality control. Recent studies have revealed their involvement in autophagy and mitophagy, and their significant impact on physiopathology.
Article
Biochemistry & Molecular Biology
Antoine Guillon, Deborah Brea-Diakite, Adeline Cezard, Alan Wacquiez, Thomas Baranek, Jerome Bourgeais, Frederic Picou, Virginie Vasseur, Lea Meyer, Christophe Chevalier, Adrien Auvet, Jose M. Carballido, Lydie Nadal Desbarats, Florent Dingli, Andrei Turtoi, Audrey Le Gouellec, Florence Fauvelle, Amelie Donchet, Thibaut Crepin, Pieter S. Hiemstra, Christophe Paget, Damarys Loew, Olivier Herault, Nadia Naffakh, Ronan Le Goffic, Mustapha Si-Tahar
Summary: Research has shown that influenza virus infection causes significant changes in lung metabolism, leading to the accumulation of succinate in respiratory fluids. Succinate exhibits powerful antiviral activity by inhibiting influenza virus replication and reducing metabolic disruptions and inflammatory responses. Administering succinate intranasally to mice reduces viral loads in the lungs and improves survival rates. The antiviral mechanism involves succinylation of viral nucleoproteins, which alters their interactions with viral RNA.
Article
Oncology
Hanane Chamma, Isabelle K. Vila, Clara Taffoni, Andrei Turtoi, Nadine Laguette
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a cancer with poor prognosis and limited response to immunotherapy. Novel strategies targeting the Stimulator of Interferon Genes (STING) protein have shown the potential to elicit response to immunotherapy. However, the effectiveness of STING activation varies depending on the cellular and tissue context, emphasizing the importance of understanding tumor heterogeneity in determining its benefits for PDAC patients.
Article
Oncology
Gilles Rademaker, Brunella Costanza, Sebastien Pyr Dit Ruys, Raphael Peiffer, Ferman Agirman, Naima Maloujahmoum, Didier Vertommen, Andrei Turtoi, Akeila Bellahcene, Vincent Castronovo, Olivier Peulen
Summary: Paladin is identified as a potential biomarker for colon cancer liver metastases, and its depletion inhibits colon cancer cell migration and metastasis.
Article
Oncology
Lindsay B. Alcaraz, Aude Mallavialle, Caroline Mollevi, Florence Boissiere-Michot, Hanane Mansouri, Joelle Simony-Lafontaine, Valerie Laurent-Matha, Thierry Chardes, William Jacot, Andrei Turtoi, Pascal Roger, Severine Guiu, Emmanuelle Liaudet-Coopman
Summary: The study reveals that SPARC expression in cancer-associated fibroblasts (CAF) is an independent prognostic marker of poor outcome in triple-negative breast cancer (TNBC). The fibroblast-secreted SPARC also has a tumor-promoting role by inhibiting TNBC cell adhesion and stimulating their motility and invasiveness.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Oncology
Margherita Puppo, Mariam Jaafar, Jean-Jacques Diaz, Virginie Marcel, Philippe Clezardin
Summary: This review discusses the roles of microRNAs and snoRNAs in the metastatic progression of cancer in bone. Dysregulation of microRNA and snoRNA expression in primary cancer cells leads to the acquisition of metastatic properties. Additionally, microRNAs and snoRNAs can act as intercellular mediators and remotely modulate the function of resident bone cells. Furthermore, the review explores the potential of microRNAs and snoRNAs as biomarkers and therapeutic targets in cancer treatments.
Article
Engineering, Biomedical
Ahmet Sen, Helene Follet, Elisabeth Sornay-Rendu, Yves Remond, Daniel George
Summary: This article proposes a theoretical numerical model to predict patient dependent osteoporotic bone degradation. The model parameters are identified through a particle swarm optimization algorithm and based on individual patient high resolution peripherical quantitative computer tomography (HRpQCT) scan data. The degradation model is based on cellular activity initiated by the elastic strain energy developed in the bone microstructure through patient's body weight. The macro and meso scale analyses are carried out and compared with in-vivo experimental bone degradation for four elderly women over a period of 10 years, showing a significant correlation and low average deviation error. The model can be easily extended to other patients and provide accurate predictions for different population categories.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2023)
Article
Engineering, Biomedical
S. Nicolle, J. -F. Palierne, D. Mitton, H. Follet, C. B. Confavreux
Summary: When considering the mechanical properties, cancerous lesions can be distinguished from healthy tissues by their frequency dependence, even if the magnitudes of the moduli are similar. The shear modulus of xenograft subcutaneous tumors grown in mice using human breast cancer cells was measured and compared to that of fat, skin, and muscle from the same mice. It was found that the tumors have a significant difference in the magnitude and frequency dependence of the shear modulus compared to the other tissues.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2023)
Article
Biochemical Research Methods
Evgenia Turtoi, Jeremy Jeudy, Sylvain Henry, Ikrame Dadi, Gilles Valette, Christine Enjalbal, Andrei Turtoi
Summary: This article introduces a new analysis protocol that includes multiple sample preparation techniques and a liquid chromatography-mass spectrometry method for the simultaneous quantitative measurement of 106 primary metabolites. The steps of bioinformatic data analysis are also described to better understand the metabolic perturbations that may occur in a biological system.
Article
Biochemical Research Methods
Evgenia Turtoi, Jeremy Jeudy, Gilles Valette, Christine Enjalbal, Isabelle K. Vila, Nadine Laguette, Andrei Turtoi
Summary: This study describes a method for simultaneously quantifying 163 polyunsaturated fatty acids (PUFAs) and their oxidized products (oxylipins) using liquid chromatography-mass spectrometry (LC-MS). The protocol provides details on PUFA purification, LC-MS analysis, and quantitative approaches for data evaluation. An example of PUFA quantification in animal tissue, along with a bioinformatic protocol, is provided for inter-sample comparison and statistical analysis.
Article
Biology
R. E. M. Y. GAUTHIER, H. E. L. E. N. E. FOLLET, ANA-MARIA TRUNFIO-SFARGHIU, D. E. L. P. H. I. N. E. FARLAY, N. I. N. A. ATTIK, S. Y. L. V. A. I. N. Meille, J. E. R. O. M. E. CHEVALIER, D. A. V. I. D. MITTON
Summary: Understanding the mechanisms of bone mechanical integrity is crucial for developing effective bone healing strategies. The matrix surrounding osteocytes, which are mechanosensitive cells responsible for bone remodeling, plays a significant role in bone repair and regeneration. However, the fluid behavior at the bone-implant interface is more complex and requires further investigation. New markers for bone mechanical integrity should be defined considering fluid behavior to improve bone biomaterial development.
