Article
Pathology
Nehal M. Atallah, Noorul Wahab, Michael S. Toss, Shorouk Makhlouf, Asmaa Y. Ibrahim, Ayat G. Lashen, Suzan Ghannam, Nigel P. Mongan, Mostafa Jahanifar, Simon Graham, Mohsin Bilal, Abhir Bhalerao, Shan E. Ahmed Raza, David Snead, Fayyaz Minhas, Nasir Rajpoot, Emad Rakha
Summary: Tumor-associated stroma in breast cancer is complex and heterogeneous. AI can provide objective morphologic assessment and identify new features. This study used AI to assess the clinical significance of stroma-to-tumor ratio and spatial arrangement, and found that high S:TR is associated with good prognosis, while heterogeneous spatial distribution of S:TR and higher tumor burden predict worse outcomes. AI provides a valuable tool for morphology assessment in breast cancer.
Article
Oncology
Minna Mutka, Reetta Virtakoivu, Kristiina Joensuu, Maija Hollmen, Paivi Heikkila
Summary: The expression of intratumoral Clever-1 + macrophages is associated with better prognosis in breast cancer. The presence of higher number of Clever-1 + cells correlates with high grade tumors and hormone receptor negative tumors, as well as with increased TILs. The findings suggest that M2 macrophages may modulate tumor stroma and maintain immune response balance to prevent excess inflammation.
BREAST CANCER RESEARCH AND TREATMENT
(2022)
Article
Chemistry, Multidisciplinary
Fotios Mpekris, Myrofora Panagi, Chrysovalantis Voutouri, John D. Martin, Rekha Samuel, Shinichiro Takahashi, Naoto Gotohda, Toshiyuki Suzuki, Panagiotis Papageorgis, Philippos Demetriou, Chryso Pierides, Laura Koumas, Paul Costeas, Motohiro Kojima, Genichiro Ishii, Anastasia Constantinidou, Kazunori Kataoka, Horacio Cabral, Triantafyllos Stylianopoulos
Summary: Nano-immunotherapy has shown potential in improving outcomes for triple negative breast cancer patients, but mechanisms of resistance need to be understood. By decompressing compressed blood vessels in lung metastases, perfusion can be restored and hypoxia alleviated, leading to more efficient delivery of nanomedicines and enhancement of anti-tumor immunity. Mechanotherapeutics in combination with nano-immunotherapy may offer synergistic effects on efficacy in breast cancer treatment.
Article
Oncology
Tao Lu, Lisa Oomens, Leon W. M. M. Terstappen, Jai Prakash
Summary: Cancer-associated fibroblasts (CAFs) are important drivers in the tumor microenvironment and facilitate the growth and survival of tumor cells, as well as metastasis formation. In this study, we aimed to study circulating CAFs (cCAFs) and circulating tumor cells (CTCs) in a preclinical breast tumor model in mice in order to understand the effect of chemotherapy on cCAFs and CTC formation. We found that tumors with CAFs grew faster than tumors without CAFs. Furthermore, chemotherapy may exacerbate the formation of cCAFs and CTCs, which may eventually support the formation of a metastasis niche in breast cancer.
Article
Biochemistry & Molecular Biology
Catharina Melzer, Juliane von der Ohe, Tianjiao Luo, Ralf Hass
Summary: Direct cellular interactions between MDA-MB-231 breast cancer cells and GFP-transduced human mesenchymal stroma/stem-like cells resulted in spontaneous cell fusion, generating breast cancer hybrid cells. These hybrid cells showed increased proliferative capacity compared to parental cells and initially remained in a dormant-like state before rapidly developing tumors. Gene expression changes and chemotherapeutic responsiveness were observed in these hybrid cells, suggesting increased tumor heterogeneity and instability in vivo phenotypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Sophie C. Hagenaars, Kiki M. H. Vangangelt, Gabi W. Van Pelt, Zsofia Karancsi, Rob A. E. M. Tollenaar, Andrew R. Green, Emad A. Rakha, Janina Kulka, Wilma E. Mesker
Summary: This paper provides a detailed description of a simple and uniform method for scoring the tumor-stroma ratio (TSR) in breast cancer using Hematoxylin and Eosin (H&E)-stained core biopsies and resection tissue. It also discusses possible histological challenges and provides suggestions to overcome them. Additionally, the paper describes the procedure for estimating TSR in lymph nodes, scoring on digital images, and the use of artificial intelligence for automatic assessment of TSR. Digitized scoring offers promising future perspectives for determining patient prognosis and response to therapy.
BREAST CANCER RESEARCH AND TREATMENT
(2022)
Article
Biochemistry & Molecular Biology
Christina Mertens, Matthias Schnetz, Claudia Rehwald, Stephan Grein, Eiman Elwakeel, Andreas Weigert, Bernhard Bruene, Michaela Jung
Summary: Macrophages in the tumor microenvironment contribute to tumor growth by secreting Lcn-2-bound iron and upregulating FPN expression. Lcn-2 plays a crucial role in tumor iron-management, affecting tumor growth progression.
Article
Engineering, Biomedical
Jaehoon Kim, Hyejin Park, Hyunho Kim, YongTae Kim, Hyun Jeong Oh, Seok Chung
Summary: Tumors create interstitial flow (IF), which allows soluble substances from cancer cells to be transported towards the tumor stroma. Researchers have designed a microfluidic device that mimics one-directional flow of IF to investigate how cancer cells activate and differentiate stromal cells.
ACTA BIOMATERIALIA
(2022)
Article
Oncology
Md Nazim Uddin, Xiaosheng Wang
Summary: This study identified tumor stroma-associated biomarkers correlated with deregulated pathways, tumor immunity, tumor progression, and clinical outcomes in breast cancer. Our findings provide new insights into the pathogenesis of breast cancer.
Article
Biochemistry & Molecular Biology
Federica Papaccio, Daniela Kovacs, Barbara Bellei, Silvia Caputo, Emilia Migliano, Carlo Cota, Mauro Picardo
Summary: Research indicates that cancer-associated fibroblasts play significant roles in tumor growth, extracellular matrix remodeling, and inflammatory response. A thorough understanding of the melanoma-fibroblast relationship can expand treatment options.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Yunus Akkoc, Kubilay Dalci, Hacer Ezgi Karakas, Secil Erbil-Bilir, Orcun Yalav, Gurhan Sakman, Faruk Celik, Soykan Arikan, Umit Zeybek, Melek Ergin, Hikmet Akkiz, Ece Dilege, Joern Dengjel, A. Isin Dogan-Ekici, Devrim Gozuacik
Summary: Macroautophagy/autophagy is a conserved cellular stress response mechanism that plays a role in supporting tumor growth and metastasis. The activation of autophagy in the tumor microenvironment by CTF1/CT-1 promotes fibroblast activation and breast cancer cell migration and invasion. Furthermore, the expression of CTF1 is correlated with autophagy in the tumor stroma and lymph node metastasis in breast cancer patients.
Article
Engineering, Biomedical
Yan Liu, Xiaodi Wu, Feifan Chen, Hao Li, Tao Wang, Ningning Liu, Kang Sun, Guangdong Zhou, Ke Tao
Summary: In this study, we found that nanoparticle-based photodynamic therapy disrupted the tumor-stroma crosstalk in pancreatic tumor models, leading to persistent inhibition of extracellular matrix secretion and enhanced therapeutic effect. By down-regulating TGF beta signaling pathways, this therapy decreased drug resistance, proliferation, and migration of cancer cells. Furthermore, it inactivated pancreatic stellate cells and hindered ECM secretion. The disruption of tumor-stroma crosstalk also improved tumor penetration in stroma-rich pancreatic tumor models, enhancing subsequent therapy outcomes.
Article
Engineering, Biomedical
Maria Heilala, Arttu Lehtonen, Ossi Arasalo, Aino Peura, Juho Pokki, Olli Ikkala, Nonappa, Juha Klefstrom, Pauliina M. Munne
Summary: Mechanically tunable 3D fibrin hydrogels are used to model the phenotypic plasticity of circulating tumor cells (CTCs)-like breast cancer cells. Cells in fibrin hydrogels show unique gene expression signatures compared to standard 3D culture conditions. The mechanical properties of the matrix regulate the cell phenotype, with stiff fibrin inducing dynamic cellular protrusions resembling prometastatic structures.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Oncology
Noorul Wahab, Michael Toss, Islam M. Miligy, Mostafa Jahanifar, Nehal M. Atallah, Wenqi Lu, Simon Graham, Mohsin Bilal, Abhir Bhalerao, Ayat G. Lashen, Shorouk Makhlouf, Asmaa Y. Ibrahim, David Snead, Fayyaz Minhas, Shan E. Ahmed Raza, Emad Rakha, Nasir Rajpoot
Summary: The study proposes an image-based prognostic marker for breast cancer that uses deep learning to objectively assess tumor heterogeneity. The marker demonstrates the ability to predict both patient survival and distant metastasis in early-stage breast cancer, with comparable accuracy to traditional manual assessment methods.
NPJ PRECISION ONCOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yasuhiro Matsumura
Summary: Despite the proven efficacy of the EPR effect in experimental mouse models, there is still a lack of awareness and utilization of this effect in clinical solid tumors. In order to overcome these limitations, Dr. Maeda proposed ways to enhance tumor vascular permeability and apply oxidative stress to tumor cells, while I proposed the use of targeted therapy specifically against the abundant stromal tissue in clinical solid cancers.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Physiology
Ying Zhong, Rose C. Mahoney, Zehedina Khatun, Howard H. Chen, Christopher T. Nguyen, Peter Caravan, Jesse D. Jr Jr Roberts
Summary: The study reveals that TGFI3 regulates LOX protein expression in newborn lung tissue via Smad2/3-dependent signaling, and implicates LOXs in the generation of excess aldehydes during neonatal lung injury.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Or Perlman, Bo Zhu, Moritz Zaiss, Matthew S. Rosen, Christian T. Farrar
Summary: This study developed an automated machine-learning-based method for the discovery of rapid and quantitative chemical exchange saturation transfer (CEST) MR fingerprinting acquisition and reconstruction protocols. The method was validated and found to be effective.
MAGNETIC RESONANCE IN MEDICINE
(2022)
Article
Biophysics
Or Perlman, Christian T. Farrar, Hye-Young Heo
Summary: This review article discusses the fundamental theory and main applications of semi-solid MT/CEST-MRF, as well as the application of artificial intelligence in image reconstruction and protocol optimization. The use of deep learning algorithms can potentially improve the performance and speed of CEST and MT MRI, addressing the challenges in clinical applications.
NMR IN BIOMEDICINE
(2023)
Article
Engineering, Biomedical
Or Perlman, Hirotaka Ito, Kai Herz, Naoyuki Shono, Hiroshi Nakashima, Moritz Zaiss, E. Antonio Chiocca, Ouri Cohen, Matthew S. Rosen, Christian T. Farrar
Summary: By utilizing deep learning, CEST-MRF can rapidly detect early apoptotic responses to oncolytic virotherapy in mice without the need for exogenous contrast agents.
NATURE BIOMEDICAL ENGINEERING
(2022)
Article
Chemistry, Inorganic & Nuclear
Rocio Uzal-Varela, Francisco Perez-Fernandez, Laura Valencia, Aurora Rodriguez-Rodriguez, Carlos Platas-Iglesias, Peter Caravan, David Esteban-Gomez
Summary: This study presents a quantitative analysis of the thermodynamic stabilities of Mn(II) complexes and identifies the contributions of different structural motifs to complex stability. The findings are helpful for designing efficient chelators for Mn(II) complexation, particularly for medical applications such as MRI contrast agents. The study also reveals that coordination number eight is more common for Mn(II) than previously assumed.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Yingying Ning, Iris Yuwen Zhou, Nicholas J. Rotile, Pamela Pantazopoulos, Huan Wang, Stephen Cole Barrett, Mozhdeh Sojoodi, Kenneth K. Tanabe, Peter Caravan
Summary: This study presents the design and synthesis of novel manganese-based MRI probes with high signal amplification for imaging liver fibrogenesis. The Mn-2CHyd probe exhibits the highest affinity and turn-on relaxivity upon reaction with Lys(Ald). A dynamic PET-MRI study demonstrates low liver uptake of the probe in healthy mice, while the probe is able to detect liver fibrogenesis in CCl4-injured mice.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biotechnology & Applied Microbiology
Darshini Kuruppu, Deepak Bhere, Christian T. Farrar, Khalid Shah, Anna-Liisa Brownell, Umar Mahmood Umar Mahmood, Kenneth K. Tanabe
Summary: This study investigates the therapeutic efficacy of oncolytic Herpes simplex virus 1 (HSV1) on different stages of breast cancer leptomeningeal metastases growth. The results show that targeting the lag and intermediate phases of the disease can inhibit tumor growth, delay symptoms onset, and extend survival.
CANCER GENE THERAPY
(2023)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Peter Caravan
JOURNAL OF MAGNETIC RESONANCE IMAGING
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Jonah Weigand-Whittier, Maria Sedykh, Kai Herz, Jaume Coll-Font, Anna N. Foster, Elizabeth R. Gerstner, Christopher Nguyen, Moritz Zaiss, Christian T. Farrar, Or Perlman
Summary: In this study, a framework based on generative adversarial networks (GAN) was designed to significantly shorten the acquisition time for quantitative three-dimensional chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) imaging, and to allow rapid reconstruction of chemical exchange parameter maps. The method was tested using datasets of L-arginine phantoms, whole-brains, and calf muscles from healthy volunteers, cancer patients, and cardiac patients, and achieved promising results.
MAGNETIC RESONANCE IN MEDICINE
(2023)
Correction
Biotechnology & Applied Microbiology
Darshini Kuruppu, Deepak Bhere, Christian T. Farrar, Khalid Shah, Anna-Liisa Brownell, Umar Mahmood, Kenneth K. Tanabe
CANCER GENE THERAPY
(2023)
Article
Chemistry, Medicinal
Sean W. McRae, Michael Cleary, Daniel DeRoche, Francisco M. Martinez, Ying Xia, Peter Caravan, Eric M. Gale, John A. Ronald, Timothy J. Scholl
Summary: In this study, five amphiphilic, anionic Mn(II) complexes were synthesized as contrast agents targeted to organic anion transporting polypeptide transporters (OATP) for liver magnetic resonance imaging (MRI). These complexes were synthesized in three steps from the commercially available trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CDTA) chelator, with T1-relaxivity ranging between 2.3 and 3.0 mM-1 s-1 at 3.0 T. The pharmacokinetics and uptake of these complexes in OATPs were assessed in vivo and in vitro, demonstrating their potential as OATP-targeted contrast agents.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cardiac & Cardiovascular Systems
Benjamin P. Bonner, Salva R. Yurista, Jaume Coll-Font, Shi Chen, Robert A. Eder, Anna N. Foster, Khoi D. Nguyen, Peter Caravan, Eric M. Gale, Christopher Nguyen
Summary: The experimental manganese-based contrast agent RVP-001 appears to be an effective alternative to gadolinium-based agents for assessing myocardial infarction location, size, and transmurality.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Chemistry, Multidisciplinary
Isabella M. Borgula, Sergey Shuvaev, Eric Abston, Nicholas J. Rotile, Jonah Weigand-Whittier, Iris Y. Zhou, Peter Caravan, Ronald T. Raines
Summary: A minimally invasive probe, [Ga-68]GaDOTA-CMP, has been developed to detect molecular changes in idiopathic pulmonary fibrosis (IPF)-associated collagen. The probe mimics the natural structure of collagen and can identify irregular collagen matrices in fibrotic lungs. The results of this study suggest that [Ga-68]GaDOTA-CMP has the potential to be useful in the early diagnosis of IPF.
Article
Gastroenterology & Hepatology
Veronica Clavijo Jordan, Mozhdeh Sojoodi, Stuti Shroff, Patricia Gonzalez Pagan, Stephen Cole Barrett, Jeremy Wellen, Kenneth K. Tanabe, Raymond T. Chung, Peter Caravan, Eric M. Gale
Summary: Imaging techniques for non-invasive diagnosis and quantification of liver inflammation are currently underdeveloped. This study investigates the potential of magnetic resonance imaging using the oxidatively activated probe Fe-PyC3A as a non-invasive biomarker for liver inflammation.
Article
Medicine, Research & Experimental
Wen Zhou, Petra Simic, Iris Y. Zhou, Peter Caravan, Xavier Vela Parada, Donghai Wen, Onica L. Washington, Maria Shvedova, Kerry A. Pierce, Clary B. Clish, Michael Mannstadt, Tatsuya Kobayashi, Marc N. Wein, Harald Juppner, Eugene P. Rhee
Summary: The mechanism of phosphate level detection in mammals involves glycolysis and synthesis of glycerol-3-phosphate (G-3-P) in the kidney, which then triggers the production of fibroblast growth factor 23 (FGF23) in the bone. This kidney-bone feedback loop controls phosphate homeostasis. The cytosolic enzyme Gpd1 and the sodium-dependent phosphate cotransporter Npt2a play essential roles in the regulation of G-3-P and FGF23 production.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
