Review
Biochemistry & Molecular Biology
Takayuki Morimoto, Tsutomu Nakazawa, Ryosuke Maeoka, Ichiro Nakagawa, Takahiro Tsujimura, Ryosuke Matsuda
Summary: Glioblastoma (GBM) is an aggressive and malignant brain tumor with poor prognosis. Various treatment strategies have been explored, including immunotherapies. However, current immunotherapies mainly based on T cells have not achieved satisfactory outcomes. This review focuses on the potential of NK cell-based immunotherapy as a novel treatment strategy for GBM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Filippo Torrisi, Simona D'Aprile, Simona Denaro, Anna Maria Pavone, Cristiana Alberghina, Agata Zappala, Rosario Giuffrida, Lucia Salvatorelli, Giuseppe Broggi, Gaetano Giuseppe Magro, Vittorio Calabrese, Nunzio Vicario, Rosalba Parenti
Summary: The central nervous system is a complex environment where glioblastoma skillfully adapts and unleashes mechanisms for its development and diffusion. Gene expression changes, epigenetic events, metabolic reprogramming, and stress responses in the tumor microenvironment contribute to genomic instability and immunosuppression that make glioblastoma invincible against immune cells and current therapies. Understanding the cellular mechanisms underlying glioblastoma resistance is crucial for planning effective therapeutic strategies.
Review
Immunology
Zide Wang, Hanlin Zhong, Xiaohong Liang, Shilei Ni
Summary: This article discusses the role of TAMs in glioblastoma, the formation of immunosuppressive tumor microenvironment, the regulation of TAM function in clinical trials, and evaluates the implications of existing and novel translational approaches for treating glioblastoma in clinical practice.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Songlei Zhou, Yukun Huang, Yu Chen, Yipu Liu, Laozhi Xie, Yang You, Shiqiang Tong, Jianpei Xu, Gan Jiang, Qingxiang Song, Ni Mei, Fenfen Ma, Xiaoling Gao, Hongzhuan Chen, Jun Chen
Summary: The authors developed a nanoplatform consisting of cannabidiol and LIGHT to improve the immune response against glioblastoma. The nanoplatform increased the number of systemic T cells and improved T-cell infiltration in GBM models, leading to successful long-term survival. This work highlights the importance of reprogramming both systemic and local immune function for T-cell based immunotherapy and provides a clinically translatable option for treating brain tumors.
NATURE COMMUNICATIONS
(2023)
Review
Neurosciences
F. Ah-Pine, M. Khettab, Y. Bedoui, Y. Slama, M. Daniel, B. Doray, P. Gasque
Summary: This review summarizes the potential roles of mesenchymal stromal cells in the context of glioblastoma and provides novel research avenues to better understand this lethal disease.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Review
Oncology
Xiao-Peng Li, Zheng-Qian Guo, Bao-Feng Wang, Min Zhao
Summary: The most frequently altered gene in glioblastoma (GBM) is the epidermal growth factor receptor (EGFR), which plays a crucial role in tumor development and anti-tumor immune response. While current molecular targeted therapies against the EGFR signaling pathway and its downstream key molecules have not shown positive clinical outcomes in GBM. However, immunotherapies, especially immune checkpoint inhibitors, have demonstrated effective anti-tumor responses in various cancers. Yet, the clinical efficacy is limited in GBM patients with EGFR alterations, implying a potential involvement of EGFR signaling in tumor immune response. Recent studies suggest that EGFR alterations not only promote GBM cell proliferation but also affect immune components in the tumor microenvironment, leading to the recruitment of immunosuppressive cells and inhibition of T and NK cell activation. Furthermore, EGFR alterations upregulate the expression of immune suppressive molecules or cytokines. This review aims to explore the role of EGFR alterations in establishing an immunosuppressive tumor microenvironment and hopes to provide a theoretical basis for combining targeted EGFR inhibitors with immunotherapy for GBM.
FRONTIERS IN ONCOLOGY
(2023)
Review
Cell Biology
Bernarda Majc, Metka Novak, Natasa Kopitar-Jerala, Anahid Jewett, Barbara Breznik
Summary: Glioblastoma, the most common brain malignant tumor in adults, poses challenges for effective immunotherapy due to its intracranial location, tumor heterogeneity, and immunosuppressive microenvironment. Various promising immunotherapeutic strategies, such as vaccines, oncolytic viruses, immune checkpoint inhibitors, and adoptive cell transfer, have been applied in an attempt to promote tumor eradication and overcome immune resistance. However, discrepancies exist between preclinical studies and clinical studies in evaluating the efficiency of these strategies on glioblastoma patients.
Article
Allergy
Aurelie Poli, Anais Oudin, Arnaud Muller, Ilaria Salvato, Andrea Scafidi, Oliver Hunewald, Olivia Domingues, Petr Nazarov, Vincent Puard, Virginie Baus, Francisco Azuaje, Gunnar Dittmar, Jacques Zimmer, Tatiana Michel, Alessandro Michelucci, Simone P. Niclou, Markus Ollert
Summary: Allergic airway inflammation delays tumor growth and improves survival in a mouse model of glioblastoma by modulating microglial gene expression and enhancing adaptive immunity.
Review
Cell Biology
Mark Dapash, David Hou, Brandyn Castro, Catalina Lee-Chang, Maciej S. Lesniak
Summary: GBM, the most common primary brain tumor in adults, has poor prognosis due to its aggressive nature; treatments, including immunotherapies, are hindered by the complex interactions within the tumor microenvironment; understanding and manipulating the different components and pressures in the TME can lead to more targeted therapies and potentially improved patient outcomes.
Article
Cell Biology
Subhajit Ghosh, Jiayi Huang, Matthew Inkman, Jin Zhang, Sukrutha Thotala, Ekaterina Tikhonova, Natalia Miheecheva, Felix Frenkel, Ravshan Ataullakhanov, Xiaowei Wang, David DeNardo, Dennis Hallahan, Dinesh Thotala
Summary: Severe and prolonged lymphopenia often occurs in glioblastoma patients after standard chemoradiotherapy, and it is associated with worse survival. A correlative study was conducted on 20 patients with glioblastoma to investigate the underlying biological mechanism of lymphopenia. The study revealed an elevated concentration of myeloid-derived suppressor cell (MDSC) regulatory genes in patients with lymphopenia after chemoradiotherapy. Further analysis confirmed increased numbers of circulating MDSC in these patients, and preclinical models demonstrated a causal relationship between radiation-induced MDSC and systemic lymphopenia. Pharmacological inhibition of MDSC effectively prevented radiation-induced lymphopenia and improved survival in the models, suggesting the potential of CB1158 and tadalafil as drugs for reducing lymphopenia in glioblastoma patients.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Myeongwoo Jung, Seungyeon Ryu, Chongtae Kim, Seongho Cha, Hoin Kang, Eunbyul Ji, Youlim Hong, Youngjoon Lee, Sukyoung Han, Seung Min Jeong, Wook Kim, Eun Kyung Lee
Summary: The RNA binding protein HuD plays a crucial role in gene expression and its dysregulation is associated with various diseases. This study investigated the differential expression of secretory proteins mediated by HuD in mouse insulinoma beta TC6 cells. The results identified endostatin and Serpin E1 as differentially expressed proteins regulated by HuD. HuD knockdown increased the expression of Col18a1, a precursor form of endostatin, and Serpin E1 by interacting with their 3’ untranslated regions. The study also revealed the role of HuD as a translational repressor. HuD downregulation in beta TC6 cells inhibited the growth and migration of islet endothelial cells, and the ectopic expression of HuD in mice affected the expression of Col18a1, Serpin E1, and markers of islet vascular cells.
CELL DEATH & DISEASE
(2022)
Review
Oncology
Roland E. Kaelin, Rainer Glass
Summary: The upregulation of Apelin and its receptor in glioblastoma plays a crucial role in tumor progression by promoting angiogenesis and tumor cell invasiveness. Targeting APLN/APLNR signaling shows promise for anti-angiogenic and anti-invasive therapy, potentially improving outcomes for patients with GBM.
Article
Oncology
Wen Ling, Sarah K. Johnson, Syed J. Mehdi, Daisy Alapat, Michael Bauer, Maurizio Zangari, Carolina Schinke, Sharmilan Thanendrarajan, Frits van Rhee, Shmuel Yaccoby
Summary: In multiple myeloma, the expression of the receptor EDNRA gradually increases with disease progression, with high-risk patients having higher expression than low-risk patients. These findings suggest that EDNRA could serve as a useful biomarker for disease progression and disrupted bone marrow vasculature. The detached EDNRA-expressing cells indicate increased angiogenesis.
Review
Cell Biology
Ana Pombero, Raquel Garcia-Lopez, Salvador Martinez
Summary: Multiple biological processes, including embryonic development and cancer progression, rely on direct intercellular interactions to regulate cell proliferation and migration. Understanding the molecular and cellular mechanisms underlying the physical interactions between cancer cells and surrounding cells is of great importance for studying tumor development and growth.
Review
Biochemistry & Molecular Biology
Ximena Vasquez, Pilar Sanchez-Gomez, Veronica Palma
Summary: Glioblastoma is the most aggressive and common primary tumor of the central nervous system, characterized by infiltrating growth and excessive vasculature. Recent studies suggest that extracellular microvesicles released by tumor cells play a role in promoting neovascularization. It is proposed that Netrin-1 may be involved in these processes and could serve as a novel biomarker for GBM progression and vascularization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Genetics & Heredity
Gabryella S. P. Santos, Alinne C. Costa, Caroline C. Picoli, Beatriz G. S. Rocha, Sheu O. Sulaiman, Debora C. Radicchi, Mauro C. X. Pinto, Miguel L. Batista, Jaime H. Amorim, Vasco A. C. Azevedo, Rodrigo R. Resende, Niels O. S. Camara, Akiva Mintz, Alexander Birbrair
Summary: Psychological stress predisposes the body to various disorders, and understanding the cellular and molecular mechanisms is crucial for successful therapeutic applications. Recent studies have found that sympathetic nerves activated by psychological stress induce brown adipocytes to produce IL-6, which promotes gluconeogenesis in hepatocytes and decreases tolerance to inflammatory organ damage. The insights from this research will be essential for managing many inflammatory diseases.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Peripheral Vascular Disease
Beatriz G. S. Rocha, Caroline C. Picoli, Bryan O. P. Goncalves, Walison N. Silva, Alinne C. Costa, Michele M. Moraes, Pedro A. C. Costa, Gabryella S. P. Santos, Milla R. Almeida, Luciana M. Silva, Youvika Singh, Marcelo Falchetti, Gabriela D. A. Guardia, Pedro P. G. Guimaraes, Remo C. Russo, Rodrigo R. Resende, Mauro C. X. Pinto, Jaime H. Amorim, Vasco A. C. Azevedo, Alexandre Kanashiro, Helder I. Nakaya, Edroaldo L. Rocha, Pedro A. F. Galante, Akiva Mintz, Paul S. Frenette, Alexander Birbrair
Summary: This study reveals the presence of perivascular GFAP+/Plp1+ cells derived from tissue-resident Schwann cells in the tumor microenvironment. Genetic ablation of Schwann cells slows down tumor growth and angiogenesis, while boosting immune surveillance by increasing tumor-infiltrating anti-tumor lymphocytes and reducing immune-suppressor cells. In humans, increased expression of Schwann cell-related genes within melanoma is associated with improved survival.
Review
Biochemistry & Molecular Biology
Patricia de Carvalho Ribeiro, Lucas Felipe Oliveira, Daniel Mendes Filho, Ricardo Cambraia Parreira, Mariana Sousa Vieira, Bruno Lemes Marques, Elis Marra da Madeira Freitas, Walison N. N. Silva, Helton da Costa Santiago, Alexander Birbrair, Henning Ulrich, Valdo Jose Dias da Silva, Rodrigo R. R. Resende
Summary: Systemic arterial hypertension is a major risk factor for cardiovascular and renal diseases, and early recognition is important for prevention. The study of biomarkers is an important approach for diagnosing and predicting hypertension and related conditions. This review discusses the use of biomarkers in hypertension and associated diseases such as ischemic stroke, intracerebral hemorrhage, transient ischemic attack, acute myocardial infarction, angina pectoris, and chronic kidney disease. Establishing a pool of potential biomarkers can improve diagnosis, prognosis, risk assessment, therapy management, and pharmacological responses to enhance patients' quality of life and prevent unfavorable outcomes.
CURRENT MEDICINAL CHEMISTRY
(2023)
Review
Cell Biology
Lucas Felipe de Oliveira, Daniel Mendes Filho, Bruno Lemes Marques, Giovana Figueiredo Maciel, Ricardo Cambraia Parreira, Jose Rodrigues do Carmo Neto, Priscilla Elias Ferreira Da Silva, Rhanoica Oliveira Guerra, Marcos Vinicius da Silva, Helton da Costa Santiago, Alexander Birbrair, Alexandre H. Kihara, Valdo Jose Dias da Silva, Talita Glaser, Rodrigo R. Resende, Henning Ulrich
Summary: Infectious diseases have significant impacts on human health globally, and there is an urgent need for a better understanding. In vitro and in vivo infection models have made significant contributions to our current knowledge of these diseases. Organoids simulate tissue architecture and function, recapitulating many characteristics of human diseases and elucidating host-pathogen interactions in various systems. In this article, we discuss the applicability of organoid technology in modeling pathogenesis, host response, and features, which can be explored for the development of preventive and therapeutic treatments.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Bruno L. Marques, Giovana Figueiredo Maciel, Marcello R. Brito Junior, Lucas D. Dias, Sergio Scalzo, Anderson K. Santos, Alexandre Hiroaki Kihara, Helton da Costa Santiago, Ricardo C. Parreira, Alexander Birbrair, Rodrigo R. Resende
Summary: As the world population's life expectancy increases, more efficient therapies are needed for neurodegenerative disorders common in old age. Neural stem cells (NSCs) play a crucial role in the development and functioning of the nervous system and have broad therapeutic applications for neurodegenerative diseases. Understanding the mechanisms that govern NSC self-renewal, differentiation, and cell signaling is essential for these therapies.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Anderson K. Santos, Sergio Scalzo, Raysa T. V. de Souza, Pedro H. G. Santana, Bruno L. Marques, Lucas F. Oliveira, M. Filho Daniel, Alexandre Hiroaki Kihara, Helton da Costa Santiago, Ricardo C. Parreira, Alexander Birbrair, Henning Ulrich, Rodrigo R. Resende
Summary: Organoid development and organ-on-a-chip are technologies that utilize stem cells to create 3D multicellular structures resembling organs and tissues in vivo. They can be strategically employed for disease modeling, drug screening, and host-pathogen studies.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Article
Neurosciences
Mariana Ribeiro Costa, Amanda Yasmin Ilario dos Santos, Tais Browne de Miranda, Rogerio Aires, Alex de Camargo Coque, Elizabeth Cristina Perez Hurtado, Maria Martha Bernardi, Vanessa Gallego Arias Pecorari, Denise Carleto Andia, Alexander Birbrair, Gilles J. Guillemin, Alexandra Latini, Rodrigo A. da Silva
Summary: Sonic Hedgehog (Shh) signaling plays a critical role in CNS development and its dysregulation leads to neurological disorders. However, the regulation of Shh signaling in the adult brain is not well understood. This study investigated the effects of DNA methylation on the transcriptional control of Shh signaling pathway members as well as its modulation by inflammation. The findings demonstrate the importance of methylation in the promoter regions of Shh pathway members in determining transcriptional patterns in the adult brain, and reveal the impact of neuroinflammation on the transcriptional control of these genes.
Article
Biotechnology & Applied Microbiology
Gabriela Munis Campos, Monique Ferrary Americo, Andria dos Santos Freitas, Fernanda Alvarenga Lima Barroso, Joyce da Cruz Ferraz Dutra, Ludmila Silva Quaresma, Barbara Fernandes Cordeiro, Juliana Guimaraes Laguna, Luis Claudio Lima de Jesus, Aparecida Maria Fontes, Alexander Birbrair, Tulio Marcos Santos, Vasco Azevedo
Summary: Using probiotics as vehicles for delivering therapeutic agents with anti-inflammatory properties through recombinant protein expression is a promising approach for preventing and treating various diseases, such as cancer and intestinal immune disorders.
PROBIOTICS AND ANTIMICROBIAL PROTEINS
(2023)
Article
Biochemistry & Molecular Biology
Salvador Sanchez-Vinces, Pedro Henrique Dias Garcia, Alex Ap. Rosini Silva, Anna Maria Alves de Piloto Fernandes, Joyce Aparecida Barreto, Gustavo Henrique Bueno Duarte, Marcia Aparecida Antonio, Alexander Birbrair, Andreia M. Porcari, Patricia de Oliveira Carvalho
Summary: The comprehensive lipidome determined by mass spectrometry is correlated to the serum whole-lipidic profile of adults with different lipidemic conditions. Specifically, serum TAG levels have a positive correlation with certain specific TAGs and ceramides, and a negative correlation with sphingomyelins. HDL-C levels are positively correlated with certain groups of glycerophosphocholine, while LDL-C has a positive correlation with sphingomyelins.
Article
Multidisciplinary Sciences
Isabella Bittencourt do Valle, Sicilia Rezende Oliveira, Janine Mayra da Silva, Gabriela Tonini Peterle, Anna Clara Gregorio Co, Sebastiao Silverio Sousa-Neto, Elismauro Francisco Mendonca, Jose Alcides Almeida de Arruda, Natalia Aparecida Gomes, Gabriel da Silva, Andreia Machado Leopoldino, Soraia Macari, Alexander Birbrair, Sandra Ventorin von Zeidler, Ivana Marcia Alves Diniz, Tarcilia Aparecida Silva
Summary: This study investigates the role of pericytes in oral squamous cell carcinoma (OSCC) and finds that they interact with neoplastic cells, influencing cancer progression and outcomes. The study characterizes pericytes in clinical samples and a mouse model of oral carcinogenesis, and shows that an increase in pericyte numbers is associated with the development of oral cancer.
SCIENTIFIC REPORTS
(2023)
Article
Instruments & Instrumentation
Ana Luiza de Castro Santos, Natalia Jordana Alves da Silva, Celso Tarso Rodrigues Viana, Leticia Cristine Cardoso dos Santos, Gabriel Henrique Costa da Silva, Sergio Ricardo Aluotto Scalzo Junior, Pedro Augusto Carvalho Costa, Walison Nunes da Silva, Itamar Couto Guedes de Jesus, Alexander Birbrair, Mariana T. Q. de Magalhaes, Frederic Frezard, Silvia Guatimosim, Rebecca M. Haley, Michael J. Mitchell, Silvia Passos Andrade, Paula Peixoto Campos, Pedro Pires Goulart Guimaraes
Summary: This study investigated the effects of the Wnt inhibitor complex CD: LGK974 on reducing the inflammatory, fibrotic, and angiogenic processes caused by intraperitoneal implants. The results showed that CD: LGK974 significantly reduced immune cell infiltration, inflammatory cytokine release, collagen deposition, and expression of pro-fibrotic markers. It also decreased VEGF levels and inhibited blood vessel formation. These findings suggest that the use of the Wnt inhibitor complex may be a potential strategy to reduce peritoneal fibrosis and implant rejection.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Article
Immunology
Patrick O. Azevedo, Natalia S. Hojo-Souza, Lidia P. Faustino, Marcilio J. Fumagalli, Isabella C. Hirako, Emiliano R. Oliveira, Maria M. Figueiredo, Alex F. Carvalho, Daniel Doro, Luciana Benevides, Edison Durigon, Flavio Fonseca, Alexandre M. Machado, Ana P. Fernandes, Santuza R. Teixeira, Joao S. Silva, Ricardo T. Gazzinelli
Summary: Current COVID-19 vaccines are effective in protecting against severe disease but not in controlling replication of the Variants of Concern (VOCs). A Spike-based DNA vaccine (pCTV-WS) was evaluated for its efficacy in protecting against different VOCs using pre-clinical models. The vaccine induced significant levels of neutralizing antibodies to Wuhan and Delta isolates but not to Gamma and Omicron variants. However, it offered significant protection to all VOCs, with T cells playing a crucial role in controlling viral replication and disease in the absence of neutralizing antibodies.
Article
Oncology
Vincent Pozorski, Yeonhee Park, Yusuf Mohamoud, Dahlia Tesfamichael, Hamid Emamekhoo, Alexander Birbrair, Mark R. Albertini, Vincent T. Ma
Summary: Neutrophil-to-lymphocyte ratios (NLR) and eosinophil counts are associated with improved survival in melanoma patients treated with immune checkpoint inhibitors. This study investigated neutrophil-to-eosinophil ratios (NER) as a predictive indicator in this population and found that lower baseline NER is associated with better treatment response and survival.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Laisa Macedo Tavares, Luis Claudio Lima de Jesus, Viviane Lima Batista, Fernanda Alvarenga Lima Barroso, Andria dos Santos Freitas, Gabriela Munis Campos, Monique Ferrary Americo, Tales Fernando da Silva, Nina Dias Coelho-Rocha, Giovanna Angeli Belo, Mariana Martins Drumond, Pamela Mancha-Agresti, Katia Duarte Vital, Simone Odilia Antunes Fernandes, Valbert Nascimento Cardoso, Alexander Birbrair, Enio Ferreira, Flaviano Santos Martins, Juliana Guimaraes Laguna, Vasco Azevedo
Summary: Intestinal mucositis is frequently observed in cancer patients undergoing chemotherapy and radiotherapy. Probiotics, prebiotics, and synbiotics have been investigated as alternative treatments for intestinal mucositis due to their anti-inflammatory properties. This study evaluated the anti-inflammatory effects of a synbiotic formulation containing L. delbrueckii CIDCA 133 and FOS in mice with 5-FU-induced intestinal mucosa inflammation. The results showed that the synbiotic formulation could modulate inflammatory parameters, protect the intestinal mucosa from damage, and improve the epithelial barrier function.
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
(2023)
Article
Cell & Tissue Engineering
Caroline C. C. Picoli, Patricia Rocha Martins, Xiao Lin Casey Wong, Thamires Righi, Pedro P. G. Guimaraes, Mauro C. X. Pinto, Jaime H. H. Amorim, Vasco A. C. Azevedo, Silma Regina Pereira, Alexandre Kanashiro, Fabio Cardoso Cruz, Rodrigo R. R. Resende, Akiva Mintz, Paul S. S. Frenette, Alexander Birbrair
Summary: Understanding the bone marrow niche is crucial for maintaining hematopoietic stem cells. This study presents a new method, called "whole bone subcutaneous transplantation", to precisely study the bone marrow niche in transgenic animals. By labeling cells, researchers were able to identify specific cellular components of the niche and found that certain cells play an important role in maintaining hematopoietic stem cells.
STEM CELL REVIEWS AND REPORTS
(2023)
