Article
Medicine, Research & Experimental
Le Huang, Huixia He, Ke Wang, Xuqian Ma, Xin Chen, Wenxin Chen, Xuan Wang, Xiaobing Jiang, Mingqian Feng
Summary: This study aims to explore the efficacy of EGFRvIII-targeted immunotoxin combined with TMZ or T cell-engaged bispecific antibody in the treatment of GBM. The results showed that this combination therapy had potent anti-tumor effects in multiple mouse models.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Aneta Wlodarczyk, Cezary Treda, Adrianna Rutkowska, Dagmara Grot, Weronika Dobrewa, Amelia Kierasinska, Marta Wegierska, Tomasz Wasiak, Tadeusz Strozik, Piotr Rieske, Ewelina Stoczynska-Fidelus
Summary: This study investigates the biological role of EGFRvIII in glioblastoma. The results suggest that EGFRvIII is not a marker of glioma stem cells and may not be a suitable target for CAR-T therapy. The effects of TGF beta and EGF in the context of EGFRvIII remain unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Joseph S. Durgin, Fraser Henderson, MacLean P. Nasrallah, Suyash Mohan, Sumei Wang, Simon F. Lacey, Jan Joseph Melenhorst, Arati S. Desai, John Y. K. Lee, Marcela Maus, Carl H. June, Steven Brem, Roddy S. O'Connor, Zev Binder, Donald M. O'Rourke
Summary: CAR T-EGFRvIII cells have shown promising results in treating patients with IDH1 wildtype recurrent glioblastoma, with one patient surviving 36 months after disease recurrence. Histopathologic analysis revealed immunosuppressive changes in tumor tissue post-infusion, along with decreased EGFRvIII expression. Serial brain imaging demonstrated reduced rCBV after CAR T treatment, suggesting potential efficacy in recurrent GBM patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Raffaella Iurlaro, Inja Waldhauer, Ester Planas-Rigol, Ester Bonfill-Teixidor, Alexandra Arias, Valeria Nicolini, Anne Freimoser-Grundschober, Isabel Cuartas, Alba Martinez-Moreno, Francisco Martinez-Ricarte, Esteban Cordero, Marta Cicuendez, Simona Casalino, Xavier Guardia-Reyes, Linda Fahrni, Thomas Poschinger, Virginie Steinhart, Marine Richard, Stefanie Briner, Joerg Mueller, Franz Osl, Johannes Sam, Sara Colombetti, Marina Bacac, Christian Klein, Estela Pineda, Luis Reyes-Figueroa, Alberto Di Somma, Josep Gonzalez, Paolo Nuciforo, Joan Carles, Maria Vieito, Josep Tabernero, Pablo Umana, Joan Seoane
Summary: T-cell bispecific antibodies (TCB) are engineered molecules that can bind both the T-cell receptor and tumor-specific antigens, showing potential therapeutic effects for EGFRvIII mutation in glioblastoma (GBM). We designed and developed a novel EGFRvIII-TCB with specificity and potent antitumor activity, promoting T-cell activation and cytokine secretion for tumor cell killing, as well as T-cell recruitment into tumors. In GBM animal models, including humanized orthotopic patient-derived xenograft models, EGFRvIII-TCB induced tumor regression. These results support the clinical testing of EGFRvIII-TCB.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Justin Choi, Zachary A. Bordeaux, Jaimie McKeel, Cory Nanni, Nishadh Sutaria, Gabriella Braun, Cole Davis, Meghan N. Miller, Martin P. Alphonse, Shawn G. Kwatra, Cameron E. West, Madan M. Kwatra
Summary: This study examined the effect of a novel anti-cancer agent, GZ17-6.02, on two types of glioblastoma stem cells. The results showed that GZ17-6.02 inhibited cell growth and downregulated pathways related to steroid synthesis and cell cycle progression. Animal experiments also demonstrated that GZ17-6.02 inhibited glioblastoma growth. The study concludes that GZ17-6.02 is a promising drug for inhibiting the growth of a subset of glioblastomas.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Shilpi Singh, Debashis Barik, Karl Lawrie, Iteeshree Mohapatra, Sujata Prasad, Afsar R. Naqvi, Amar Singh, Gatikrushna Singh
Summary: The mTOR signaling pathway plays a crucial role in glioblastoma, but inhibiting it poses challenges. This article discusses potential targets and strategies for mTOR inhibitor development, as well as optimized drug delivery systems and personalized treatment approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Fei Tong, Ji-xing Zhao, Zi-yuan Fang, Xiao-teng Cui, Dong-yuan Su, Xing Liu, Jun-hu Zhou, Guang-xiu Wang, Zhi-jun Qiu, Shi-zhong Liu, Jun-qi Fu, Chun-sheng Kang, Jia-chong Wang, Qi-xue Wang
Summary: Based on CRISPR-Cas9 library screening, we found that MUC1-C is essential for EGFRvIII glioma cell survival and TMZ resistance. By inhibiting the NF-kappa B pathway, EPIC-1027 disrupts the EGFRvIII-MUC1-C positive feedback loop, inhibits glioma progression, and increases sensitivity to TMZ.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Oncology
Youri Hoogstrate, Santoesha A. Ghisai, Maurice de Wit, Iris de Heer, Kaspar Draaisma, Job van Riet, Harmen J. G. van de Werken, Vincent Bours, Jan Buter, Isabelle Vanden Bempt, Marica Eoli, Enrico Franceschi, Jean-Sebastien Frenel, Thierry Gorlia, Monique C. Hanse, Ann Hoeben, Melissa Kerkhof, Johan M. Kros, Sieger Leenstra, Giuseppe Lombardi, Slavka Lukacova, Pierre A. Robe, Juan M. Sepulveda, Walter Taal, Martin Taphoorn, Rene M. Vernhout, Annemiek M. E. Walenkamp, Colin Watts, Michael Weller, Filip Y. F. de Vos, Guido W. Jenster, Martin van den Bent, Pim J. French
Summary: This study investigated the role of EGFRvIII in glioblastoma using multiple datasets. The results showed significant variations in EGFRvIII expression ratios among tumors. EGFRvIII expression was inversely correlated with pan-EGFR expression and exhibited higher potency in downstream pathway activation. Glioblastomas with EGFRvIII had a lower incidence of CDK4 or MDM2 amplification compared to EGFRvIII-negative tumors.
Article
Biochemistry & Molecular Biology
Cezary Treda, Aneta Wlodarczyk, Marcin Pacholczyk, Adrianna Rutkowska, Ewelina Stoczynska-Fidelus, Amelia Kierasinska, Piotr Rieske
Summary: The number of glioblastoma cases is increasing, but current therapies are ineffective. This study shows that the use of L8A4 antibody with tyrosine kinase inhibitors does not affect its interaction with EGFRvIII and can increase epitope display. The extracellular part of EGFRvIII has plasticity in forming disulfide bridges within monomers and dimers, allowing the L8A4 antibody to recognize both forms. Immunotherapy using L8A4 antibody, combined with TKIs, can potentially improve anti-GB therapy success.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Adrianna Rutkowska, Tadeusz Strozik, Krystyna Jedrychowska-Danska, Alicja Zamerska, Dorota Jesionek-Kupnicka, Tamara Kowalczyk, Waldemar Och, Blazej Szostak, Cezary Treda, Aneta Wlodarczyk, Amelia Kierasinska-Kalka, Tomasz Wasiak, Damian Ciunowicz, Piotr Rieske, Ewelina Stoczynska-Fidelus
Summary: This study evaluates the use of the L8A4 antibody in detecting EGFRvIII and compares it with other methods. The results indicate that Real-time PCR is a highly specific and sensitive method, and L8A4 antibody shows certain specificity in immunocytochemistry.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Alan T. Yeo, Hyun Jung Jun, Vicky A. Appleman, Piyan Zhang, Hemant Varma, Jann N. Sarkaria, Al Charest
Summary: EGFRvIII plays a crucial role in GBM, relying on co-stimulatory signaling from PDGFRA. The use of kinase inhibitors in combination can effectively suppress EGFRvIII-expressing GBM.
Article
Chemistry, Multidisciplinary
Jordi Ribera, Clara Vilches, Vanesa Sanz, Ignacio de Miguel, Irene Portoles, Bernat Cordoba-Jover, Esther Prat, Virginia Nunes, Wladimiro Jimenez, Romain Quidant, Manuel Morales-Ruiz
Summary: Liver fibrosis is a significant health issue with limited treatment options. Targeting hepatic stellate cells and using gold nanorods may be promising strategies for reducing fibrosis. Gold nanorods have shown potential in decreasing fibrosis, hepatic inflammation, and hepatocyte injury.
Article
Biochemistry & Molecular Biology
Hee-Jin Kim, Jeong-Yub Kim, Chan-Woong Jung, Young-Sun Lee, Joon-Yong An, Eun Ho Kim, Ki-Hong Kim, Sang Pyung Lee, Jae-Yong Park, Myung-Jin Park
Summary: ANO1 interacts with EGFRvIII, increases its protein stability, and supports the maintenance of stemness and tumor progression in GSCs; knockdown of ANO1 can suppress self-renewal and invasion activities in GSCs.
Article
Oncology
Paula Aldaz, Jaione Auzmendi-Iriarte, Maika Durantez, Irene Lasheras-Otero, Estefania Carrasco-Garcia, M. Victoria Zelaya, Laura Bragado, Ana Olias-Arjona, Larraitz Egana, Nicolas Sampron, Idoia Morilla, Marta Redondo-Munoz, Mikel Rico, Massimo Squatrito, Marta Maria-Alonso, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Inaki M. Larrayoz, Claudia Wellbrock, Ander Matheu, Imanol Arozarena
Summary: The study identified a novel mechanism induced by dexamethasone in GBM cells, suggesting that tyrosine kinase inhibitors could potentially improve the treatment of GBM by overcoming the radio-protective and pro-proliferative effects of dexamethasone. Experiments confirmed that dexamethasone down-regulates genes controlling cell cycle checkpoints and overrides certain cellular mechanisms, while also up-regulating PDGFR signaling to promote cell survival during extended mitosis.
Article
Biochemistry & Molecular Biology
Nurmaya Effendi, Kenji Mishiro, Kazuhiro Shiba, Seigo Kinuya, Kazuma Ogawa
Summary: This study aimed to develop peptide-based imaging probes for PDGFRβ and examined the effects of different linkers on their properties. The in vivo evaluation showed certain probes with higher cell uptake rates and stability, but insufficient tumor accumulation, calling for further probe modification for better in vivo imaging.
Review
Biochemistry & Molecular Biology
Monica Fedele, Riccardo Sgarra, Sabrina Battista, Laura Cerchia, Guidalberto Manfioletti
Summary: The transition between epithelial and mesenchymal phenotype plays a key role in tumor cell invasion and metastasis. This process, known as epithelial-mesenchymal transition (EMT) and its reverse process called mesenchymal-epithelial transition (MET), is closely associated with metabolic changes and successful cancer progression. This review focuses on the complex interaction between EMT and metabolism during tumor progression, with a particular emphasis on cancer stem cells and Long non-coding RNAs (LncRNAs). Specific cancers such as breast, lung, and thyroid cancer are also discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Biotechnology & Applied Microbiology
Monica Fedele, Oreste Gualillo, Andrea Vecchione
BIOMED RESEARCH INTERNATIONAL
(2022)
Article
Pharmacology & Pharmacy
Simona Camorani, Silvia Tortorella, Lisa Agnello, Chiara Spanu, Annachiara D'Argenio, Roberto Nilo, Antonella Zannetti, Erica Locatelli, Monica Fedele, Mauro Comes Franchini, Laura Cerchia
Summary: This study presents a novel aptamer-based platform for the targeted delivery of siRNA to triple-negative breast cancer cells. By utilizing cell-targeting and internalizing aptamers, this delivery system specifically delivers siRNA to TNBC cells, resulting in efficient suppression of PD-L1 expression.
Article
Chemistry, Physical
C. Russo, A. Carpentieri, A. Tregrossi, A. Ciajolo, B. Apicella
Summary: This study found that different classes of carbon dots (CDs) with different fluorescence characteristics can be synthesized in the same flame system by selecting appropriate residence time. The fluorescence lifetimes and quantum yields of pyrogenic CDs were measured for the first time, providing useful parameters for discriminating the fluorescent components and inferring their structural properties.
Article
Cell Biology
Annachiara Sarnella, Ylenia Ferrara, Sandra Albanese, Daniela Omodei, Laura Cerchia, Giuseppina De Simone, Claudiu T. Supuran, Antonella Zannetti
Summary: Conventional chemotherapy is the main treatment for TNBC patients, but drug resistance is common. This study showed that BM-MSCs and CA IX play a role in reducing cisplatin sensitivity in TNBC. Inhibiting CM-MSC-induced CA IX using SLC-0111 enhanced chemotherapy efficacy and inhibited TNBC cell migration and invasion.
Article
Biochemistry & Molecular Biology
Riccardo Sgarra, Sabrina Battista, Laura Cerchia, Guidalberto Manfioletti, Monica Fedele
Summary: Histone lactylation, a newly discovered histone modification, is an important hallmark of cancer cells that links metabolic changes to gene expression reprogramming. Further research on the competition mechanism between lactylation and acetylation, as well as the mechanisms by which lactate fluctuation controls specific gene sets in tissues, is needed to develop new anticancer therapeutic approaches.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Biochemistry & Molecular Biology
Denise Bonente, Laura Bianchi, Rossana De Salvo, Claudio Nicoletti, Elena De Benedetto, Tommaso Bacci, Luca Bini, Giovanni Inzalaco, Lorenzo Franci, Mario Chiariello, Gian Marco Tosi, Eugenio Bertelli, Virginia Barone
Summary: Epiretinal membranes (ERMs) are pathological tissues that form in the vitreoretinal interface, leading to vision loss. Understanding the molecular dysfunctions that contribute to ERM development is crucial. Our bioinformatics study identified CD44 as a central regulator of ERM dynamics, and its interaction with PDPN could promote migration in epithelial cells. PDPN, overexpressed in various cancers, plays a relevant role in fibrotic and inflammatory pathologies, modulating signaling pathways involved in ERM formation. Understanding the role of PDPN may open new therapeutic options for fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Lisa Agnello, Annachiara d'Argenio, Roberto Nilo, Monica Fedele, Simona Camorani, Laura Cerchia
Summary: Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor outcomes, is highly immunogenic, suggesting immunotherapy is a viable strategy. Recently, effective aptamer-based strategies have been developed to enhance or restore the anticancer immune response in TNBC.
Article
Oncology
Stefano Luca, Renato Franco, Antonella Napolitano, Valeria Soria, Andrea Ronchi, Federica Zito Marino, Carminia Maria Della Corte, Floriana Morgillo, Alfonso Fiorelli, Antonio Luciano, Giuseppe Palma, Claudio Arra, Sabrina Battista, Laura Cerchia, Monica Fedele
Summary: Lung cancer, especially non-small cell lung cancer (NSCLC), has a high mortality rate and lacks effective therapies. Immunotherapy shows promise, but predicting success is challenging. This study investigated the relationship between PATZ1 and PD-L1 expression in NSCLC and found that they are negatively associated. PATZ1 overexpression downregulates PD-L1 expression and inhibits NSCLC cell proliferation, migration, and invasion, suggesting it may act as a tumor suppressor in NSCLC.
Article
Cell Biology
Lisa Agnello, Annachiara d'Argenio, Alessandra Caliendo, Roberto Nilo, Antonella Zannetti, Monica Fedele, Simona Camorani, Laura Cerchia
Summary: Triple-negative breast cancer (TNBC) is an aggressive subtype that often becomes resistant to chemotherapy. This study identifies TIMP-1 as a potential biomarker for TNBC chemoresistance and suggests that blocking TIMP-1 signaling could be a viable treatment strategy.
Article
Biochemistry & Molecular Biology
Simona Camorani, Annachiara d'Argenio, Lisa Agnello, Roberto Nilo, Antonella Zannetti, Luis Exequiel Ibarra, Monica Fedele, Laura Cerchia
Summary: This study identifies three truncated RNA aptamers that can effectively recognize and target triple-negative breast cancer cells. These aptamers have excellent nuclease resistance and rapidly internalize into acidic compartments, interfering with the growth of tumor cells. The aptamers are considered promising anti-tumor agents and targeted delivery nanovectors for triple-negative breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)