Article
Biology
Etsuko Yamamoto Hattori, Tatsuya Masuda, Yohei Mineharu, Masamitsu Mikami, Yukinori Terada, Yasuzumi Matsui, Hirohito Kubota, Hidemasa Matsuo, Masahiro Hirata, Tatsuki R. Kataoka, Tatsutoshi Nakahata, Shuji Ikeda, Susumu Miyamoto, Hiroshi Sugiyama, Yoshiki Arakawa, Yasuhiko Kamikubo
Summary: Interfering with RUNX family proteins can reduce the growth of glioblastoma in mice and identify pathways involved in tumor growth maintenance. Specifically, the study reveals that RUNX1, a transcription factor, downregulates p21 by enhancing the expressions of BIRC5 and PIF1, thus conferring anti-apoptotic properties on glioblastoma. Gene switch-off therapy targeting RUNX1 shows promising results by decreasing the expression levels of BIRC5 and PIF1, inducing apoptosis and cell cycle arrest. This pathway may serve as a therapeutic target for glioblastoma.
COMMUNICATIONS BIOLOGY
(2022)
Article
Oncology
Jixing Zhao, Shixue Yang, Xiaoteng Cui, Qixue Wang, Eryan Yang, Fei Tong, Biao Hong, Menglin Xiao, Lei Xin, Can Xu, Yanli Tan, Chunsheng Kang
Summary: Researchers have discovered a small-molecule inhibitor called EPIC-0412 that enhances the effectiveness of the chemotherapy drug TMZ in treating GBM. By disrupting DNA damage repair pathways and targeting MGMT, EPIC-0412 sensitizes GBM cells to TMZ and induces cell cycle arrest and apoptosis. The study also shows that EPIC-0412 epigenetically silences MGMT through specific pathways.
Article
Oncology
Lei Xin, Yanli Tan, Yuanxue Zhu, Xiaoteng Cui, Qixue Wang, Jixing Zhao, Shaohui Tian, Can Xu, Menglin Xiao, Biao Hong, Jianglong Xu, Xiaoye Yuan, Changsheng Wang, Chunsheng Kang, Chuan Fang
Summary: This study identified a potential small-molecule inhibitor, EPIC-0307, that selectively disrupted the PRADX-EZH2 interaction to upregulate expressions of tumor suppressor genes, thereby exerting its antitumor effects on GBM cells. EPIC-0307 treatment also increased the chemotherapeutic efficacy of TMZ by epigenetically downregulating DNA repair-associated genes and MGMT expression in GBM cells.
Article
Neurosciences
Songwang Xie, Zhen Hong, Yan Li, Junyong Wang, Jian Wang, Shaoquan Li, Yongchang Liu
Summary: The study found that RNF216 is overexpressed in GBM and is associated with a poor prognosis. Overexpression of RNF216 promotes GBM cell growth and inhibits apoptosis, while knockdown of RNF216 has the opposite effects. RNF216 overexpression also degrades the p53 protein and negatively regulates the p53 pathway.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Cell Biology
Cyntanna C. Hawkins, Amber B. Jones, Emily R. Gordon, Yuvika Harsh, Julia K. Ziebro, Christopher D. Willey, Corinne Griguer, David K. Crossman, Sara J. Cooper, Sasanka Ramanadham, Ninh Doan, Anita B. Hjelmeland
Summary: Sphingolipid metabolism is dysregulated in GBM, leading to cell evasion of apoptosis. This study found that the mRNA levels of acid ceramidase, a key enzyme in S1P production, were elevated in recurrent GBM. Inhibiting acid ceramidase decreased cell growth and increased apoptosis in TMZ-resistant GBM cells, suggesting the potential utility of targeting sphingolipid metabolism in recurrent GBM.
CELL DEATH DISCOVERY
(2023)
Article
Cell Biology
Elena Navarro-Carrasco, Pedro A. Lazo
Summary: Depletion of the chromatin kinase VRK1 using RNA interference reduces glioblastoma cell dependence on temozolomide and olaparib, promoting tumor cell death.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Martin Glas, Matthew T. Ballo, Ze'ev Bomzon, Noa Urman, Shay Levi, Gitit Lavy-Shahaf, Suriya Jeyapalan, Terence T. Sio, Paul M. DeRose, Martin Misch, Sophie Taillibert, Zvi Ram, Andreas F. Hottinger, Jacob Easaw, Chae-Yong Kim, Suyash Mohan, Roger Stupp
Summary: TTFields treatment affects the rate of distant progression in newly diagnosed GBM patients, with distant lesions appearing further from the primary lesion in the TTFields treatment arm. Distant progression correlates with improved clinical outcomes in TTFields patients.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Article
Oncology
Weifeng Lv, Qi Li, Bo Jia, Yalong He, Yi Ru, Qingdong Guo, Xia Li, Wei Lin
Summary: The study reveals that DEC1 regulates TMZ resistance through the SP1-MGMT axis, influencing cell apoptosis in GBM. The expression levels of DEC1 are correlated with MGMT in glioma tissues, indicating its predictive value in TMZ resistance and poor prognosis.
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
(2021)
Article
Cell Biology
Daniela Hanisch, Andrea Krumm, Tamara Diehl, Carla M. Stork, Mario Dejung, Falk Butter, Ella Kim, Walburgis Brenner, Gerhard Fritz, Thomas G. Hofmann, Wynand P. Roos
Summary: This study reports a novel mechanism by which overexpression of class I HDACs increases resistance of glioblastoma cells to TMZ. HDACs promote the bypass of O-6-methylguanine DNA lesions by enhancing RAD18 expression, leading to resistance to TMZ treatment.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Alessandro Tancredi, Olga Gusyatiner, Pierre Bady, Michelle C. Buri, Remy Lomazzi, Davide Chiesi, Mahmoud Messerer, Monika E. Hegi
Summary: Bromodomain and extra-terminal tail (BET) proteins are potential epigenetic targets in cancer, including glioblastoma. BET inhibitors disrupt the histone code-gene transcription link. BET-induced differential gene expression in glioblastoma derived-spheres revealed 6 distinct response patterns. The O-6-methylguanine-DNA methyltransferase (MGMT) gene, a known resistance factor for glioblastoma treatment, showed consistent downregulation in response to BET inhibitors.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Natasha Carmell, Ola Rominiyi, Katie N. Myers, Connor McGarrity-Cottrell, Aurelie Vanderlinden, Nikita Lad, Eva Perroux-David, Sherif F. El-Khamisy, Malee Fernando, Katherine G. Finegan, Stephen Brown, Spencer J. Collis
Summary: Glioblastomas are high-grade brain tumors with low patient survival rates, and current treatment options are limited. Targeting ERK5 has been shown to enhance the effectiveness of the chemotherapeutic drug temozolomide in killing tumor cells, potentially providing clinical benefits for glioblastoma patients in the future.
Article
Oncology
Mario Caccese, Matteo Simonelli, Veronica Villani, Simona Rizzato, Tamara Ius, Francesco Pasqualetti, Marco Russo, Roberta Ruda, Rosina Amoroso, Luisa Bellu, Roberta Bertorelle, Francesco Cavallin, Angelo Dipasquale, Mariantonia Carosi, Stefano Pizzolitto, Daniela Cesselli, Pasquale Persico, Beatrice Casini, Matteo Fassan, Vittorina Zagonel, Giuseppe Lombardi
Summary: The study investigated the association between MGMT promoter methylation status and overall survival in glioblastoma patients, finding better survival when MGMT > 15% but a more complex, non-linear relationship between MGMT methylation and survival.
Article
Oncology
Mustafa Guven, Filiz Taspinar, Farika Nur Denizler-Ebiri, Javier S. Castresana, Mehmet Taspinar
Summary: Glioblastoma is a highly aggressive and deadly form of brain cancer. Current treatments have not yet achieved the desired outcomes, leading to the investigation of alternative therapies. This study aimed to determine the potential therapeutic effect of combining the chemotherapy drug temozolomide (TMZ) with the histone deacetylase inhibitor trichostatin A (TSA) for glioblastoma treatment.
Article
Biochemistry & Molecular Biology
Ji-Young Yoo, Margaret Yeh, Yin-Ying Wang, Christina Oh, Zhong-Ming Zhao, Balveen Kaur, Tae-Jin Lee
Summary: The study demonstrated that overexpression of miR-138 sensitizes GBM cells to TMZ treatment and increases apoptotic cell death. Mechanistically, miR-138 directly repressed Survivin expression to enhance apoptosis induced by TMZ.
Article
Oncology
Shaofang Wu, Xiaolong Li, Feng Gao, John F. de Groot, Dimpy Koul, W. K. Alfred Yung
Summary: This study demonstrates the critical role of PARylation of MGMT by PARP in repairing TMZ-induced O-6-MetG, with PARP inhibitors reducing MGMT function and sensitizing GBM to TMZ. The findings provide a rationale for combining PARP inhibitors to enhance TMZ sensitivity in MGMT-unmethylated GBM.
Article
Endocrinology & Metabolism
Margherita Maffei, Antonio Giordano
Summary: Leptin, produced by white adipose tissue, plays a crucial role in informing the brain about energy stores and regulating energy balance. Obesity-induced alterations in certain hubs of the hypothalamus may hinder the action of Leptin, leading to resistance in obese patients. Understanding how Leptin gains access to the brain and how neuronal plasticity interferes with its function may provide insights for enhancing the effects of Leptin.
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
(2022)
Review
Pharmacology & Pharmacy
Diletta Rosati, Antonio Giordano
Summary: Single-cell RNA sequencing technologies play a crucial role in understanding cancer heterogeneity and lineage-dependent drug resistance.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Riccardo Di Fiore, Sherif Suleiman, Rosa Drago-Ferrante, Yashwanth Subbannayya, Francesca Pentimalli, Antonio Giordano, Jean Calleja-Agius
Summary: Cervical cancer is the fourth most common gynecological malignancy worldwide, mostly associated with high-risk human papillomavirus infection. While cervical Pap smear screening and vaccines have effectively reduced the incidence and death rate of cervical cancer, their accessibility varies across different societies. Prognosis for advanced or recurrent cervical cancer is poor, with a maximum one-year relative survival rate of 20%. Cancer stem cells may play a crucial role in the tumorigenesis, metastasis, relapse, and resistance to treatment of cervical cancer, highlighting their potential as therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Pierluigi Scalia, Stephen J. Williams, Yoko Fujita-Yamaguchi, Antonio Giordano
Summary: The IGFs are important growth factors that play a key role in cell growth and cell cycle progression through their cellular receptors. Understanding the intracellular signaling mechanisms of IGFs is crucial for cancer research. This study provides a comprehensive summary of the current understanding of the regulatory mechanisms of IGFs in cancer and suggests new perspectives for further research.
Article
Anatomy & Morphology
Ilenia Severi, Silvia Abbatelli, Jessica Perugini, Eleonora Di Mercurio, Martina Senzacqua, Antonio Giordano
Summary: This study is the first comprehensive morphological investigation into the distribution and physiological role of BChE in the mouse gastrointestinal tract. BChE-positive cells were found in various digestive organs, such as the stomach, liver, and intestine, and were closely linked to ghrelin production.
JOURNAL OF ANATOMY
(2023)
Review
Microbiology
Elena Rossi, Luciano Mutti, Andrea Morrione, Antonio Giordano
Summary: SARS-CoV-2 infection can lead to interstitial pneumonia and neurological symptoms, especially in elderly patients prone to cytokine storm and severe outcomes like acute respiratory distress syndrome. Limited understanding exists on the correlation between symptoms and clinical outcomes, as well as virus-host interactions.
Article
Biochemistry & Molecular Biology
A. Giordano, F. Cinti, R. Canese, G. Carpinelli, G. Colleluori, A. Di Vincenzo, G. Palombelli, I Severi, M. Moretti, C. Redaelli, J. Partridge, M. C. Zingaretti, A. Agostini, F. Sternardi, A. Giovagnoni, S. Castorina, S. Cinti
Summary: Obesity is a major cause of death worldwide, and understanding the adipose organ is crucial for studying its pathology and formulating therapeutic strategies. This study utilized various techniques such as anatomical dissections and medical imaging to demonstrate that white and brown adipose tissues form a large, unified structure that can be considered a true organ. This finding was confirmed in both mice and humans.
Review
Biochemistry & Molecular Biology
Giovanni Ciccarelli, Stefano Conte, Giovanni Cimmino, Patrizia Maiorano, Andrea Morrione, Antonio Giordano
Summary: Atherosclerosis is a complex disease involving metabolic processes and inflammation. Despite improved therapies, a significant residual risk remains due to unmet therapeutic targets. Endothelial dysfunction and lipid infiltration are primary causes of atherosclerotic plaque progression. Mitochondrial dysfunction can affect arterial wall cells, leading to oxidative stress, chronic inflammation, and intracellular lipid deposition. Evaluating mitochondrial defects through the detection and characterization of mitochondrial DNA (mtDNA) is crucial, and mitochondria-targeting therapies show promise in treating atherosclerosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Susan Costantini, Elena Di Gennaro, Francesca Capone, Alfonso De Stefano, Guglielmo Nasti, Carlo Vitagliano, Sergio Venanzio Setola, Fabiana Tatangelo, Paolo Delrio, Francesco Izzo, Antonio Avallone, Alfredo Budillon
Summary: This study aimed to evaluate whether the integration of plasma metabolomics and lipidomics combined with the analysis of a large panel of plasma cytokines can be used to predict the risk of relapse and other patient outcomes after liver surgery. The results showed the potential of these combined biomarker approaches to predict outcomes in colorectal cancer patients.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Elisa Ventura, Giacomo Ducci, Reyes Benot Dominguez, Valentina Ruggiero, Antonino Belfiore, Elena Sacco, Marco Vanoni, Renato V. V. Iozzo, Antonio Giordano, Andrea Morrione
Summary: Progranulin plays an important pro-tumorigenic role in various solid tumors and has diagnostic and prognostic values in multiple tumor types. The molecular mechanisms underlying progranulin's function in cancer are not fully understood, but recent evidence suggests a strong context-dependency of progranulin signaling. This review focuses on summarizing the current evidence supporting the pro-oncogenic role of progranulin and its molecular mechanisms of action in cancer.
Review
Cell Biology
Riccardo Di Fiore, Sherif Suleiman, Rosa Drago-Ferrante, Yashwanth Subbannayya, Sarah Suleiman, Mariela Vasileva-Slaveva, Angel Yordanov, Francesca Pentimalli, Antonio Giordano, Jean Calleja-Agius
Summary: The FBXW7 protein plays a role in regulating cellular growth and acts as a tumor suppressor. It is a component of the SCF complex and aids in the degradation of oncoproteins via the UPS. FBXW7 mutations are associated with cancer and could potentially serve as diagnostic and prognostic biomarkers. This review aims to provide an update on the role of FBXW7 as a potential biomarker and therapeutic target, particularly in gynecologic cancers.
Review
Agriculture, Dairy & Animal Science
Giovanna Liguori, Anna Costagliola, Renato Lombardi, Orlando Paciello, Antonio Giordano
Summary: Animal-assisted interventions (AAIs) are planned activities carried out in multidisciplinary teams with educational, therapeutic, and recreational purposes. These interventions offer many advantages to subjects but may expose them to zoonotic-pathogen transmission. Therefore, ensuring positive animal welfare and implementing preventive measures are crucial for the safety of patients.
Review
Biochemistry & Molecular Biology
Alfredo Caturano, Margherita D'Angelo, Andrea Mormone, Vincenzo Russo, Maria Pina Mollica, Teresa Salvatore, Raffaele Galiero, Luca Rinaldi, Erica Vetrano, Raffaele Marfella, Marcellino Monda, Antonio Giordano, Ferdinando Carlo Sasso
Summary: Oxidative stress plays a critical role in the development and progression of diabetes and its associated complications. The imbalance between reactive oxygen species (ROS) production and the body's antioxidant defense mechanisms leads to cellular damage and dysfunction. By understanding and addressing oxidative stress, it may be possible to alleviate the burden of diabetes and improve patient outcomes.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Letter
Oncology
Pierpaolo Correale, Francesca Pentimalli, Valerio Nardone, Antonio Giordano, Luciano Mutti