Review
Biochemistry & Molecular Biology
Geoffrey Brown
Summary: This review investigates how oncogenes contribute to the development of malignant tumors, with the cancer stem cell theory suggesting that cancer is a hierarchical structure of cells derived from transformed stem cells. It examines the loss of intrinsic versatility in stem cells, the role of proto-oncogenes in cell lineage determination, and the impact of epigenetic events in regulating cell fate and tumor development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Genevieve M. M. Abd, Madison C. C. Laird, Jennifer C. C. Ku, Yong Li
Summary: Cancer stem cells are a subset of cells within tumors that can self-renew and differentiate into different cancer cell types. It is believed that they may originate from normal stem cells that have undergone genetic mutations or epigenetic changes. Recent research has also shown that cancer cells can dedifferentiate into stem-like cells. Understanding the mechanisms behind these cells' formation is crucial for the development of new strategies in cancer treatment and therapies.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Larischa de Wet, Anthony Williams, Marc Gillard, Steven Kregel, Sophia Lamperis, Lisa C. Gutgesell, Jordan E. Vellky, Ryan Brown, Kelly Conger, Gladell P. Paner, Heng Wang, Elizabeth E. Platz, Angelo M. De Marzo, Ping Mu, Jonathan L. Coloff, Russell Z. Szmulewitz, Donald J. Vander Griend
Summary: This study investigated the impact of SOX2 expression on patient outcomes and its function within prostate cancer cells. The results revealed that SOX2 expression promotes metastatic progression and therapy resistance in prostate cancer, and affects the metabolic pathways and metabolites of cancer cells. These findings contribute to a better understanding of the role of SOX2 in prostate cancer and suggest its potential as a biomarker and pharmacologic target in clinical settings.
Review
Oncology
Amirhosein Faghihkhorasani, Alaleh Dalvand, Ehsan Derafsh, Farnaz Tavakoli, Nada Khairi Younis, Saman Yasamineh, Omid Gholizadeh, Pooria Shokri
Summary: Cancer Stem Cells (CSCs) play a crucial role in tumor initiation, growth, metastasis, and recurrence. Viral infections, such as human papillomaviruses, hepatitis B virus, Epstein-Barr virus, and hepatitis C virus, have been found to promote the aggressiveness of cancer by supporting the development of CSC features. Oncolytic viruses (OVs) are a promising class of cancer therapeutics that selectively replicate in tumor cells, induce immunogenic cell death, and promote antitumor immunity. Understanding the effects of viral infection on CSC development and the suppression of CSCs by OV therapy is of great importance for cancer management and treatment.
CANCER CELL INTERNATIONAL
(2023)
Review
Biochemistry & Molecular Biology
Geoffrey Brown
Summary: There is a need for agents to target cancer stem cells in order to effectively treat cancer and prevent relapse and metastasis, as conventional therapies often spare these cells. Targeting retinoic acid receptor (RAR)gamma is a promising approach, as it is selectively expressed in primitive cells and has been implicated in various human cancers. Antagonizing RAR gamma shows potential in inducing necroptosis in cancer stem cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Ferenc Sipos, Gyorgyi Muzes
Summary: Inflammatory processes and cancer stem cells (CSCs) play important roles in tumorigenesis. CSCs are associated with cancer properties such as metastasis, treatment resistance, and disease recurrence. This review explores the reciprocal interplay between CSCs and immune cells in the tumor microenvironment, highlighting how CSCs influence leukocyte reprogramming and promote pro-tumor immune cells. The study also emphasizes the potential of immune cells in eliminating CSCs, while addressing the immune evasion mechanisms in CSCs and their clinical implications.
Article
Materials Science, Multidisciplinary
Anish Hiresha Verma, Swarna Ganesh, Krishnan Venkatakrishnan, Bo Tan
Summary: This study used ultra-small gold nanoparticles as a nanoscale probe to demethylate the genomic DNA of cancer stem cells, leading to their reprogramming into cancer cells. The results showed a significant decrease in genetic and phenotypic stemness as well as cell cycle quiescence of lung cancer stem cells. This research opens up new avenues for effective anti-cancer treatments and precision nanomedicine.
APPLIED MATERIALS TODAY
(2023)
Review
Oncology
Martina Addeo, Giuseppina Di Paola, Henu Kumar Verma, Simona Laurino, Sabino Russi, Pietro Zoppoli, Geppino Falco, Pellegrino Mazzone
Summary: Gastric cancer stem cells play a crucial role in the initiation and progression of gastric cancer, with features like self-renewal capability and resistance to current anticancer therapies. Targeting metabolic pathways of cancer stem cells could be a promising strategy in cancer therapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Wen Bu, Yi Li
Summary: Mouse mammary glands are composed of ductal trees lined with epithelial cells, which are responsible for mammary gland function and tumorigenesis. Intraductal injection of a viral vector carrying genes of interest into the mouse mammary ductal tree is a critical step for evaluating gene function and generating tumor models. Lentiviral, retroviral, adenoviral, or AAV vectors can be used for this purpose. This study demonstrates the delivery of a gene of interest into mammary epithelial cells using intraductal injection of a viral vector, showing stable expression and oncogene-induced lesions and tumors.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Cell Biology
Qiong Xiao, Chen-Yu Wang, Chuan Gao, Ji-Dong Chen, Jing-Jing Chen, Zhen Wang, Lin-Gao Ju, Shan-Bo Tang, Jie Yao, Feng Li, Lian-Yun Li, Min Wu
Summary: The study reveals that TRIM11 regulates the tumorigenesis and development of breast cancer by degrading KDM5C, and the expression of TRIM11 is negatively correlated with KDM5C in breast cancer patients.
CELL DEATH & DISEASE
(2022)
Review
Endocrinology & Metabolism
Ila Tewari Jasra, Nerea Cuesta-Gomez, Kevin Verhoeff, Braulio A. Marfil-Garza, Nidheesh Dadheech, A. M. James Shapiro
Summary: This review summarizes the roles and mechanisms of mitochondria in somatic cell reprogramming to iPSCs and the metabolic shift associated with directed differentiation into pancreatic beta-like cells.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Wen Bu, Yi Li
Summary: Mouse mammary glands have ductal trees lined by epithelial cells with one opening at each nipple. Introducing genes into these epithelial cells is crucial for studying gene function and generating mammary tumor models. This can be done by intraductal injection of a viral vector carrying the genes. Different types of viral vectors can be used, such as lentiviruses and retroviruses. This study demonstrates the delivery of genes of interest into mammary epithelial cells using intraductal injection of a viral vector, and the subsequent expression and effects of these genes.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Biochemistry & Molecular Biology
Avina Rami, Lukasz Laczmanski, Jagoda Jackow-Nowicka, Joanna Jackow
Summary: A model for studying the development of RDEB-cSCC was established using cellular reprogramming and re-differentiation technology. RNA-seq analysis revealed distinct gene expression signatures and functional changes in RDEB-cSCC subjected to reprogramming and re-differentiation, offering a valuable tool to study cSCC and identify potential therapeutic targets for RDEB-cSCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Luke R. Lemmerman, Maria H. H. Balch, Jordan T. Moore, Diego Alzate-Correa, Maria A. Rincon-Benavides, Ana Salazar-Puerta, Surya Gnyawali, Hallie N. Harris, William Lawrence, Lilibeth Ortega-Pineda, Lauren Wilch, Ian B. Risser, Aidan J. Maxwell, Silvia Duarte-Sanmiguel, Daniel Dodd, Gina P. Guio-Vega, Dana M. McTigue, W. David Arnold, Shahid M. Nimjee, Chandan K. Sen, Savita Khanna, Cameron Rink, Natalia Higuita-Castro, Daniel Gallego-Perez
Summary: Intracranial delivery of EFF-nanotransfected fibroblasts resulted in a dose-dependent increase in perfusion 14 days post injection. Mice treated with EFF-nanotransfected fibroblasts showed around 70% infarct resolution and up to 90% motor recovery. Immunohistological analysis confirmed increased vascularity, neuronal cellularity, and reduced glial scar formation in response to treatment with EFF-nanotransfected fibroblasts, suggesting a promising strategy for ischemic stroke treatment.
Review
Biochemistry & Molecular Biology
Dongwei Li, Xiaodong Shu, Ping Zhu, Duanqing Pei
Summary: Recent research has shown that chromatin dynamics are closely linked to cell fate control, with a binary off/on switch occurring during iPSC reprogramming. This implies that similar mechanisms may also be present in normal development, suggesting potential for further approaches to directing cell fate changes.
Article
Hematology
Javier Raboso-Gallego, Ana Casado-Garcia, Xiaoyu Jiang, Marta Isidro-Hernandez, Andrew J. Gentles, Shuchun Zhao, Yaso Natkunam, Oscar Blanco, Veronica Dominguez, Belen Pintado, Diego Alonso-Lopez, Javier De las Rivas, Carolina Vicente-Duenas, Izidore S. Lossos, Isidro Sanchez-Garcia
Summary: The study shows that constitutive enforced expression of HGAL leads to DLBCL development, and this protein is mainly present in germinal center B lymphocytes.
Article
Immunology
Eleni Louka, Benjamin Povinelli, Alba Rodriguez-Meira, Gemma Buck, Wei Xiong, Guanlin Wang, Nikolaos Sousos, Neil Ashley, Angela Hamblin, Christopher A. G. Booth, Anindita Roy, Natalina Elliott, Deena Iskander, Josu de la Fuente, Nicholas Fordham, Sorcha O'Byrne, Sarah Inglott, Ruggiero Norfo, Mariolina Salio, Supat Thongjuea, Anupama Rao, Irene Roberts, Adam J. Mead
Summary: Juvenile myelomonocytic leukemia (JMML) is a childhood leukemia with poor prognosis caused by RAS-pathway mutations. The cellular hierarchy of JMML is complex, with LSCs present in HSPCs, providing new avenues for monitoring and treating the disease.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Cell Biology
Anindita Roy, Guanlin Wang, Deena Iskander, Sorcha O'Byrne, Natalina Elliott, Jennifer O'Sullivan, Gemma Buck, Elisabeth F. Heuston, Wei Xiong Wen, Alba Rodriguez Meira, Peng Hua, Anastasios Karadimitris, Adam J. Mead, David M. Bodine, Irene Roberts, Bethan Psaila, Supat Thongjuea
Summary: Human hematopoiesis is a dynamic process that starts in utero 18-21 days post-conception, and understanding the site- and stage-specific variations is crucial for unraveling the origin of hematological disorders. The comparison of 57,489 HSPCs from 5 different tissues revealed significant transitions in cellular architecture and gene regulatory networks at different locations and developmental stages, with hematopoietic stem cells showing progression from cycling to quiescence during ontogeny. The dataset was also useful for understanding aberrant hematopoiesis in comparison to two cancers that present at distinct time points in postnatal life.
Article
Oncology
Ana Casado-Garcia, Marta Isidro-Hernandez, Ninad Oak, Andrea Mayado, Christine Mann-Ran, Javier Raboso-Gallego, Silvia Aleman-Arteaga, Alexandra Buhles, Dario Sterker, Elena G. Sanchez, Jorge Martinez-Cano, Oscar Blanco, Alberto Orfao, Diego Alonso-Lopez, Javier De Las Rivas, Susana Riesco, Pablo Prieto-Matos, Africa Gonzalez-Murillo, Francisco Javier Garcia Criado, Maria Begona Garcia Cenador, Thomas Radimerski, Manuel Ramirez-Orellana, Cesar Cobaleda, Jun J. Yang, Carolina Vicente-Duenas, Andreas Weiss, Kim E. Nichols, Isidro Sanchez-Garcia
Summary: This study demonstrates that early-life administration of the JAK1/2 inhibitor ruxolitinib significantly reduces the risk of B-ALL in mice. This finding presents a potential strategy for preventing the development of B-ALL.
Article
Multidisciplinary Sciences
Wen Hao Neo, Yiran Meng, Alba Rodriguez-Meira, Muhammad Z. H. Fadlullah, Christopher A. G. Booth, Emanuele Azzoni, Supat Thongjuea, Marella F. T. R. de Bruijn, Sten Eirik W. Jacobsen, Adam J. Mead, Georges Lacaud
Summary: The study reveals the crucial role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE. Loss of EZH2 activity in HE leads to the generation of non-functional EMPs due to a lack of Wnt signaling downregulation, while the generation of primitive erythroid cells is not affected. EZH2 is essential for the generation of functional EMPs at the onset of the endothelial-to-hematopoietic transition but becomes dispensable later on.
NATURE COMMUNICATIONS
(2021)
Letter
Oncology
Claudia Saitta, Stefano Rebellato, Laura Rachele Bettini, Giovanni Giudici, Nicolo Panini, Eugenio Erba, Valentina Massa, Franziska Auer, Ulrike Friedrich, Julia Hauer, Andrea Biondi, Grazia Fazio, Giovanni Cazzaniga
BLOOD CANCER JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Marta Isidro-Hernandez, Silvia Aleman-Arteaga, Ana Casado-Garcia, Belen Ruiz-Corzo, Susana Riesco, Pablo Prieto-Matos, Jorge Martinez-Cano, Lucia Sanchez, Cesar Cobaleda, Isidro Sanchez-Garcia, Carolina Vicente-Duenas
Summary: Leukemia is the most common cancer in children, with B-cell acute lymphoblastic leukemia (B-ALL) being the most prevalent form. The development of pediatric leukemia is believed to occur through a multi-step or multi-hit mechanism, including prenatal and postnatal steps. Although many initiating events for childhood leukemia occur in utero at a higher frequency than the actual incidence of the disease, the reason why only a small percentage of children with these preleukemic hits develop full-blown leukemia remains unknown. Mouse models that replicate the multi-step process of childhood B-ALL will be crucial in identifying environmental or other factors associated with an increased risk of the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Letter
Oncology
Adela Escudero, Masatoshi Takagi, Franziska Auer, Ulrike Anne Friedrich, Satoshi Miyamoto, Atsushi Ogawa, Kohsuke Imai, Barbara Pascual, Maria Vela, Polina Stepensky, Layal Yasin, Sarah Elitzur, Arndt Borkhardt, Antonio Perez-Martinez, Julia Hauer
Article
Oncology
Rabea Wagener, Carolin Walter, Franziska Auer, Deya Alzoubi, Julia Hauer, Ute Fischer, Julian Varghese, Martin Dugas, Arndt Borkhardt, Triantafyllia Brozou
Summary: Through whole-exome sequencing, we identified CHEK2 germline variants in 32/418 (7.7%) pediatric cancer patients, with 46.8% of them having leukemia. Functional analysis revealed that 5 pathogenic variants impaired CHK2 protein function. In conclusion, CHEK2 variants increase the risk for not only adult-onset but also pediatric cancer.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Oncology
Laura C. C. Godfrey, Alba Rodriguez-Meira
Summary: This review outlines the recent advances in technology that enable the study of epigenetic mechanisms in blood cells with greater precision and resolution. The study of these mechanisms is crucial for understanding normal blood cell function and disease development. The new technologies allow for specific epigenetic changes to be introduced and the study of individual cells, providing a new lens for exploring epigenetic regulation.
Article
Hematology
Nadine Ruechel, Marina Oldenburg, Stefan Janssen, Aleksandra A. Pandyra, Wei Liu, Eleni Vasileiou, Daniel Hein, Vera Helena Jepsen, Ute Fischer, Daniel Picard, Gesine Koegler, Julia Hauer, Franziska Auer, Angelina Beer, Ortwin Adams, Colin MacKenzie, Martin Jaeger, Mihai G. Netea, Arndt Borkhardt, Katharina L. Gossling
Article
Genetics & Heredity
Ulrike A. Friedrich, Marc Bienias, Claudia Zinke, Maria Prazenicova, Judith Lohse, Arne Jahn, Maria Menzel, Jonas Langanke, Carolin Walter, Rabea Wagener, Triantafyllia Brozou, Julian Varghese, Martin Dugas, Miriam Erlacher, Evelin Schrock, Meinolf Suttorp, Arndt Borkhardt, Julia Hauer, Franziska Auer
Summary: This study assessed the efficacy of clinical checklists in detecting genetic cancer predisposition in children with cancer, and found that the clinical checklist showed high sensitivity in identifying cancer predisposition, but there were still limitations.
GENETICS IN MEDICINE
(2023)
Article
Genetics & Heredity
Alba Rodriguez-Meira, Ruggiero Norfo, Sean Wen, Agathe L. Chedeville, Haseeb Rahman, Jennifer O'Sullivan, Guanlin Wang, Eleni Louka, Warren W. Kretzschmar, Aimee Paterson, Charlotte Brierley, Jean-Edouard Martin, Caroline Demeule, Matthew Bashton, Nikolaos Sousos, Daniela Moralli, Lamia Subha Meem, Joana Carrelha, Bishan Wu, Angela Hamblin, Helene Guermouche, Florence Pasquier, Christophe Marzac, Francois Girodon, William Vainchenker, Mark Drummond, Claire Harrison, J. Ross Chapman, Isabelle Plo, Sten Eirik W. Jacobsen, Bethan Psaila, Supat Thongjuea, Ileana Antony-Debre, Adam J. Mead
Summary: This study analyzes hematopoietic stem/progenitor cells from patients with secondary acute myeloid leukemia (sAML) transforming from myeloproliferative neoplasm. They find that chronic inflammation suppresses TP53 wild-type cells while enhancing the fitness advantage of TP53-mutant cells, promoting genetic evolution. These findings will aid in the development of risk-stratification, early detection, and treatment strategies for TP53-mutant leukemia.
Review
Immunology
Cesar Cobaleda, Carolina Vicente-Duenas, Isidro Sanchez-Garcia
Summary: B cell acute lymphoblastic leukaemia (B-ALL) is the most common form of childhood cancer, but treatment still fails in a significant percentage of patients. Studies have shown that a small percentage of healthy newborns carry preleukaemic clones, but only a small proportion of them will progress to overt leukemia.
NATURE REVIEWS IMMUNOLOGY
(2021)