Article
Immunology
Rajeev Dhupar, Katherine E. Jones, Amy A. Powers, Seth H. Eisenberg, Kai Ding, Fangyuan Chen, Cecile Nasarre, Zhanpeng Cen, Yi-Nan Gong, Amanda C. LaRue, Elizabeth S. Yeh, James D. Luketich, Adrian V. Lee, Steffi Oesterreich, Michael T. Lotze, Robert M. Gemmill, Adam C. Soloff
Summary: Tumor-associated macrophages (TAMs) play a significant role in breast cancer progression, and the neuropilin-2 (NRP2) isoforms NRP2a and NRP2b have been found to regulate TAM functionality. The expression levels of NRP2a and NRP2b in TAMs are influenced by the location of the tumor, and they are closely associated with TAM infiltration in both primary and metastatic breast cancers. This study also demonstrates that NRP2a and NRP2b have distinct functionality in macrophages and are associated with different TAM subsets in breast cancer.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yaser Gamallat, Hend Zaaluk, Ealia Khosh Kish, Ramy Abdelsalam, Konstantinos Liosis, Sunita Ghosh, Tarek A. Bismar
Summary: ARPC1B is found to play a role in the invasion and metastasis of prostate cancer, and is associated with ERG and PTEN. High expression of ARPC1B is related to the aggressiveness and prognosis of PCa.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Susanne G. Kidd, Mari Bogaard, Kristina T. Carm, Anne Cathrine Bakken, Aase M. V. Maltau, Marthe Lovf, Ragnhild A. Lothe, Karol Axcrona, Ulrika Axcrona, Rolf I. Skotheim
Summary: This study aimed to determine the prognostic value of candidate biomarkers transcriptional regulator ERG and related ETS family genes in prostate cancer, while considering tumor heterogeneity. The results showed that ERG protein has independent prognostic value in predicting biochemical and clinical recurrence of prostate cancer, and appears to have the greatest prognostic value for patients with Grade Groups 4-5.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Cheng Qian, Dan Li, Yu Chen
Summary: The ETS family of proteins plays critical roles in prostate cancer, and gene fusion and overexpression of certain members have been linked to the development of this cancer. This review provides an overview of the discovery, classification, and therapeutic targeting of ETS family members in prostate cancer.
Article
Oncology
Tilman D. Rachner, Sabine Kasimir-Bauer, Andy Goebel, Kati Erdmann, Oliver Hoffmann, Martina Rauner, Lorenz C. Hofbauer, Rainer Kimmig, Ann-Kathrin Bittner
Summary: sNRP-1 levels are weakly correlated with age in breast cancer patients, with higher levels in peri- and postmenopausal patients compared to premenopausal patients; low sNRP-1 levels are associated with a significant survival benefit.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Cell Biology
Mari Bogaard, Rolf Skotheim, Aase Maltau, Susanne G. Kidd, Ragnhild A. Lothe, Karol Axcrona, Ulrika Axcrona
Summary: Our study aims to determine the relative contribution of cribriform pattern, reactive stroma (RS), PTEN, Ki67, ERG, and CAPRA-S score in predicting prostate cancer prognosis. The results show that cribriform pattern and Ki67 are independent predictors of biochemical recurrence (BCR) and clinical recurrence (CR), while ERG expression is an independent predictor of CR. Additionally, cribriform pattern has the highest relative proportion of explained variation for predicting BCR (11%), and Ki67 has the highest relative proportion of explained variation for CR (21%).
Article
Cell Biology
Peng Zhang, Liang Chen, Fenfang Zhou, Zhiwen He, Gang Wang, Yongwen Luo
Summary: Prostate cancer (PCa) is a common male malignancy with unclear progression mechanisms. This study found that NRP1, highly expressed in PCa, was associated with poor prognosis in PCa patients. Functionally, NRP1 depletion inhibited PCa cell proliferation and migration, while NRP1 overexpression promoted these processes. Mechanistically, NRP1 was regulated by HIF1 alpha and interacted with EGFR, leading to EGFR phosphorylation and activation of the AKT signaling pathway, promoting PCa progression. Additionally, the NRP1 inhibitor EG01377 inactivated the EGFR/AKT signaling axis and suppressed PCa progression.
CELL DEATH & DISEASE
(2023)
Article
Pathology
Yuri Tolkach, Romina Zarbl, Simone Bauer, Manuel Ritter, Joerg Ellinger, Stephan Hauser, Laura Hueser, Sabine M. Klauck, Peter Altevogt, Holger Sultmann, Dimo Dietrich, Glen Kristiansen
Summary: CD24 is overexpressed in many human cancers, including prostate cancer, and its up-regulation can be influenced by DNA methylation of the CD24 promoter. Higher levels of CD24 expression are associated with poorer outcomes in prostate cancer patients, including shorter biochemical recurrence-free survival. Overexpression of ERG and PTEN deficiency are also correlated with increased CD24 expression levels in prostate cancer.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yaser Gamallat, Andrea Bakker, Ealia Khosh Kish, Muhammad Choudhry, Simon Walker, Saood Aldakheel, Sima Seyedi, Kuo-Cheng Huang, Sunita Ghosh, Geoffrey Gotto, Tarek A. Bismar
Summary: This study evaluated the expression of CDK2AP1 gene in prostate cancer patients and found it is related to clinical prognosis. High CDK2AP1 expression is associated with worse overall survival and cause-specific survival. Through data analysis, researchers discovered that CDK2AP1 can directly interact with p53, which is consistent with the clinical data.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Wendy Montero-Ovalle, Maria C. Sanabria-Salas, Jorge Mesa-Lopez de Mesa, Rodolfo Varela-Ramirez, Yenifer Y. Segura-Moreno, Santiago A. Sanchez-Villalobos, Marcela Nunez-Lemus, Martha L. Serrano
Summary: Prostate cancer (PCa) is a highly prevalent and fatal cancer worldwide. Current prognostic markers for PCa do not effectively distinguish between aggressive and indolent forms. Molecular subtypes, such as TMPRSS2-ERG, SPOP, FOXA1, and IDH1, have been identified, but their association with prognosis in PCa remains unclear. The frequency of these subtypes in Colombian patients is also unknown.
CELL BIOLOGY INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Qiong Wang, Junxiu Chen, Sandeep Singh, Zhongqiu Xie, Fujun Qin, Xinrui Shi, Robert Cornelison, Hui Li, Hai Huang
Summary: This study examined the landscape of chimeric RNAs in different types of prostate cancer cell lines and identified chimeric RNAs specifically expressed in neuroendocrine prostate cancer (NEPC). Experimental validation and in silico analysis showed that these chimeric RNAs may serve as biomarkers for tumor malignancy and poor clinical prognosis.
CELL AND BIOSCIENCE
(2022)
Article
Multidisciplinary Sciences
Eva Shrestha, Jonathan B. Coulter, William Guzman, Busra Ozbek, Megan M. Hess, Luke Mummert, Sarah E. Ernst, Janielle P. Maynard, Alan K. Meeker, Christopher M. Heaphy, Michael C. Haffner, Angelo M. De Marzo, Karen S. Sfanos
Summary: The study suggests that bacterial infections may initiate driver gene alterations in prostate cancer, with infection-induced ERG+ fusions being an early alteration in the carcinogenic process, potentially originating from proliferative inflammatory atrophy as a precursor.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
Francesca Lorenzin, Francesca Demichelis
Summary: In addition to its role in development and in the vascular and hematopoietic systems, ERG plays a central role in prostate cancer. Inhibiting ERG activity may be a significant step in improving treatment efficacy for patients with ERG-positive prostate tumors.
Article
Oncology
Yingchun Liang, Enlin Rong, Jin Qian, Chenkai Ma, Jimeng Hu
Summary: In this study, the researchers analyzed the transcriptome of 231 patients with metastatic prostate cancer and identified four distinct biological subtypes. They found that the luminal subtype had higher androgen receptor expression and copy number alterations, while genes in the HRR pathway were downregulated in most subtypes except HRR and NE subtypes. The researchers also found that the basal subtype had a higher frequency of the TMPRSS2-ERG fusion.
PROSTATE CANCER AND PROSTATIC DISEASES
(2022)
Article
Pathology
Eric Erak, Lia DePaula Oliveira, Adrianna A. Mendes, Oluwademilade Dairo, Onur Ertunc, Ibrahim Kulac, Javier A. Baena-Del Valle, Tracy Jones, Jessica L. Hicks, Stephanie Glavaris, Gunes Guner, Igor Damasceno Vidal, Mark Markowski, Claire de la Calle, Bruce J. Trock, Avaneesh Meena, Uttara Joshi, Chaith Kondragunta, Saikiran Bonthu, Nitin Singhal, Angelo M. De Marzo, Tamara L. Lotan
Summary: Microscopic examination of prostate cancer has not found a consistent association between molecular and morphologic features. However, deep-learning algorithms trained on hematoxylin and eosin (H & E)-stained whole slide images may be better than human eyes at screening for clinically-relevant genomic alterations. These algorithms can identify prostate tumors with ETS-related gene (ERG) fusions or PTEN deletions.
Article
Endocrinology & Metabolism
Tilman D. Rachner, Cornelia S. Link-Rachner, Martin Bornhaeuser, Lorenz C. Hofbauer
Summary: Patients who undergo allogeneic hematopoietic cell transplantation (HCT) are at an increased risk of developing bone loss due to various factors, including the disease itself and the applied therapies. This review provides an overview of the underlying mechanisms and offers screening and treatment recommendations for managing this complication.
Article
Hematology
Franziska Hettler, Christina Schreck, Sandra Romero Marquez, Thomas Engleitner, Baiba Vilne, Theresa Landspersky, Heike Weidner, Renate Hausinger, Ritu Mishra, Rupert Oellinger, Martina Rauner, Ronald Naumann, Christian Peschel, Florian Bassermann, Roland Rad, Rouzanna Istvanffy, Robert A. J. Oostendorp
Summary: Chronic inflammation and aging remodel the bone marrow microenvironment, leading to reduced hematopoietic stem cell (HSC) function. In this study, a mouse model with Sfrp1 gene deletion in osteolineage cells was established to investigate the mechanisms of HSC decline and potential strategies to counteract it. The results showed that HSC from these mice had diminished repopulating activity, DNA damage, increased expression of reactive oxygen species pathway, and reduced proliferation. Treatment with IQ-1, which inhibited the phosphorylation of p300, restored HSC function by reducing the association of beta-catenin/phosphop300 and decreasing nuclear p300 in OS1(Delta/Delta) mice. These findings highlight the essential role of osteoprogenitor Sfrp1 in maintaining HSC function and provide a new strategy to restore poor HSC function by downregulating the nuclear beta-catenin/phospho-p300 association.
Article
Endocrinology & Metabolism
Aliya A. Khan, Mishaela R. Rubin, Peter Schwarz, Tamara Vokes, Dolores M. Shoback, Claudia Gagnon, Andrea Palermo, Claudio Marcocci, Bart L. Clarke, Lisa G. Abbott, Lorenz C. Hofbauer, Lynn Kohlmeier, Susanne Pihl, Xuebei An, Walter Frank Eng, Alden R. Smith, Jenny Ukena, Christopher T. Sibley, Aimee D. Shu, Lars Rejnmark
Summary: TransCon PTH demonstrated efficacy in maintaining normocalcemia and allowing independence from conventional therapy in individuals with hypoparathyroidism. The treatment also showed significant improvements in health-related quality of life and hypoparathyroidism-related symptoms.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Endocrinology & Metabolism
Eva Maria Woelfel, Franziska Lademann, Haniyeh Hemmatian, Stephane Blouin, Phaedra Messmer, Lorenz C. Hofbauer, Bjoern Busse, Martina Rauner, Katharina Jaehn-Rickert, Elena Tsourdi
Summary: Hyperthyroidism causes secondary osteoporosis by promoting bone resorption. Osteocytic osteolysis and elevated tartrate-resistant acid phosphatase (TRAP) activity were observed in hyperthyroid mice. The bone microarchitecture and turnover recovered after treatment, but the osteocytic osteolysis effects were not reversed.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Engineering, Biomedical
Sofie Dragoun Kolibova, Eva Maria Woelfel, Haniyeh Hemmatian, Petar Milovanovic, Herbert Mushumba, Birgit Wulff, Maximilian Neidhardt, Klaus Pueschel, Antonio Virgilio Failla, Annegreet Vlug, Alexander Schlaefer, Benjamin Ondruschka, Michael Amling, Lorenz C. Hofbauer, Martina Rauner, Bjoern Busse, Katharina Jaehn-Rickert
Summary: Type 1 diabetes mellitus (T1DM) is associated with increased bone fragility. Our study found accelerated osteocyte apoptosis and local mineralization in T1DM patients, suggesting that T1DM speeds up bone aging and impairs its biomechanical competence. Dysfunction of the osteocyte network hampers bone remodeling and repair, contributing to the increased fracture risk in T1DM individuals.
ACTA BIOMATERIALIA
(2023)
Article
Endocrinology & Metabolism
Manuel Gado, Annett Heinrich, Denise Wiedersich, Katrin Sameith, Andreas Dahl, Vasileia I. Alexaki, Michael M. Swarbrick, Ulrike Baschant, Ingo Grafe, Nikolaos Perakakis, Stefan R. Bornstein, Martina Rauner, Lorenz C. Hofbauer, Holger Henneicke
Summary: This study demonstrates that activation of the sympathetic nervous system through cold exposure or selective I33-adrenergic receptor agonist can alleviate the adverse metabolic effects caused by chronic glucocorticoid exposure. Cold exposure preserves the function of brown adipose tissue and reverses white adipose tissue lipid accumulation, correcting obesity, hyperinsulinemia, and hyperglycemia caused by glucocorticoids.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Engineering, Biomedical
Gloria Ruiz-Gomez, Juliane Salbach-Hirsch, Jan-Niklas Duerig, Linda Koehler, Kanagasabai Balamurugan, Sandra Rother, Sophie-Luise Heidig, Stephanie Moeller, Matthias Schnabelrauch, Giulia Furesi, Sophie Paehlig, Pedro M. Guillem-Gloria, Christine Hofbauer, Vera Hintze, M. Teresa Pisabarro, Joerg Rademann, Lorenz C. Hofbauer
Summary: The WNT signaling pathway is important for bone development and regeneration, and abnormalities in WNT ligands and inhibitors are associated with various bone diseases. This study focused on glycosaminoglycan (GAG) recognition by DKK1, a WNT inhibitor, and aimed to develop WNT signaling regulators. Through a multidisciplinary approach, researchers designed and synthesized GAG derivatives with improved neutralizing properties for DKK1. These derivatives showed increased WNT pathway activity and improved bone regeneration in experimental models. The findings suggest that rationally engineered GAG variants could be used as novel therapeutic approaches.
Article
Biochemistry & Molecular Biology
Maria G. Ledesma-Colunga, Ulrike Baschant, Heike Weidner, Tiago C. Alves, Peter Mirtschink, Lorenz C. Hofbauer, Martina Rauner
Summary: In this study, the authors investigated the role of transferrin receptor 2 (Tfr2) in the pathogenesis of inflammatory arthritis. They found that Tfr2-deficient mice developed more severe joint inflammation and bone erosion compared to control mice. Further experiments suggested that Tfr2 deficiency promoted macrophage polarization towards a pro-inflammatory state, contributing to the progression of arthritis.
Article
Endocrinology & Metabolism
Souad Daamouch, Sylvia Thiele, Lorenz Hofbauer, Martina Rauner
Summary: The link between obesity and low bone strength is a significant medical concern. Previous research has shown that Dkk1, a Wnt inhibitor, is upregulated in bone tissue in obesity and drives obesity-induced bone loss. This study investigated the role of adipogenic Dkk1 in bone homeostasis and obesity-induced bone loss in mice. The results suggest that adipogenic Dkk1 plays a transient role in bone mass regulation during adolescence, but does not contribute to bone homeostasis or obesity-induced bone loss later in life.
ENDOCRINE CONNECTIONS
(2023)
Article
Medicine, General & Internal
Athanasios D. Anastasilakis, Stergios A. Polyzos, Panagiotis A. Vorkas, Athina Gkiomisi, Maria P. Yavropoulou, Martina Rauner, Panagiotis Nikolakopoulos, Stergios Papachatzopoulos, Polyzois Makras, Spyridon Gerou, Lorenz C. Hofbauer, Andrea Palermo, Elena Tsourdi
Summary: Menstrual cessation affects lipid metabolism. This study evaluated the effects of goserelin-induced menstrual cessation and subsequent menstrual restoration on lipid metabolism. The results showed that levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein A1 increased during menstrual cessation, but remained unchanged during menstrual restoration.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Mahdi Jaber, Lorenz C. Hofbauer, Christine Hofbauer, Georg N. Duda, Sara Checa
Summary: Bone regeneration is impaired in type 2 diabetes mellitus (T2DM), with alterations in MSC proliferation, migration, and osteoblast differentiation playing a significant role. Mechanical changes have minimal impact on reduced bone regeneration in T2DM. These findings have clinical implications for the treatment of bone fractures in patients with T2DM.
Article
Medicine, Research & Experimental
Lorenz C. Hofbauer, Franziska Lademann, Martina Rauner
Summary: Osteocytes, senescent cells implicated in bone loss disorders, have been shown to be effectively cleared through systemic senolysis, preventing age-related bone loss and mitigating bone marrow adiposity. Cell-specific senolysis in osteocytes alone had only a partial effect. Surprisingly, transplantation of senescent fibroblasts into young mice led to osteocyte senescence and bone loss. These findings on osteocyte senescence and the effects of remote senolysis suggest potential strategies against multisystem aging.
JOURNAL OF CLINICAL INVESTIGATION
(2023)