Review
Chemistry, Medicinal
Ranju Bansal, Anjleena Malhotra
Summary: Cancer is a serious health issue with available chemotherapeutic drugs being highly toxic and lacking selectivity. Advances in science have illuminated molecular pathways responsible for cancer, leading to the development of targeted anticancer agents, such as quinazoline derivatives. These agents act by inhibiting various protein kinases and other molecular targets, offering new opportunities for more effective cancer treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Hyunjoo Kim, Muhah Jeong, Do-Hyeong Na, Shin-Hyeon Ryu, Eun Il Jeong, Kwangmin Jung, Jaemin Kang, Ho-June Lee, Taebo Sim, Dae-Yeul Yu, Hee Chul Yu, Baik-Hwan Cho, Yong-Keun Jung
Summary: The study reveals that AK2 functions as a suppressor of BRAF, regulating its activity in response to cellular metabolic state. AK2 interacts with BRAF and inhibits its activity and downstream ERK phosphorylation. The research also finds that low expression of AK2 and increased ERK activation are associated with hepatocellular carcinoma (HCC), and loss of AK2 promotes tumor growth and BRAF activity.
CELL DEATH & DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Jingtong Zhao, Zhijun Luo
Summary: The Ras-Raf-MEK-ERK signaling pathway plays essential roles in cell proliferation, survival, differentiation, and development. The mechanisms of A-Raf and C-Raf activation are still not completely understood, while B-Raf is frequently mutated in many cancers. Understanding the regulation of Raf kinases is of great importance in tumorigenesis and cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nutrition & Dietetics
Sara Salucci, Alberto Bavelloni, Anna Bartoletti Stella, Francesco Fabbri, Ivan Vannini, Manuela Piazzi, Karyna Volkava, Katia Scotlandi, Giovanni Martinelli, Irene Faenza, William Blalock
Summary: Approximately 7% of childhood cancers and 1% of adult cancers are soft tissue sarcomas, with rhabdomyosarcoma being the most common subtype. Despite current therapeutic protocols, survival rates for RMS have not improved significantly in the past decade. Curcumin, derived from the Curcuma longa plant, has low toxicity and has shown anti-tumorigenic effects in vitro. This study evaluated curcumin's activity in RMS cell lines and identified the major pathways affected by curcumin's anti-tumorigenic effects. Curcumin treatment resulted in cell cycle arrest, inhibited migration and colony formation, and induced apoptosis. Proteome profiler analysis revealed that curcumin primarily influenced signaling through AKT-mTOR, STAT, AMPK, and p53 pathways in a subtype-specific manner. Combinational therapeutic targeting of these pathways may be the best option for RMS treatment.
Review
Biochemistry & Molecular Biology
Damiano Cirri, Francesco Bartoli, Alessandro Pratesi, Emma Baglini, Elisabetta Barresi, Tiziano Marzo
Summary: This article provides an overview of research approaches to improve metal-based agents for cancer and infection treatments. Despite the success of approved inorganic drugs in tumor chemotherapy, the discovery and clinical application of new inorganic drugs are slow and limited due to pharmaceutical industry influences.
Review
Biochemistry & Molecular Biology
Liuchunyang Yu, Zhenglai Hua, Xinyi Luo, Ting Zhao, Yuanyan Liu
Summary: Albumin, as the most abundant plasma protein, plays a crucial role in the transport and efficacy of chemotherapeutic drugs. It affects drug outcomes, toxicity, tumor proliferation, and metabolism by binding to exogenous and endogenous ligands, such as fatty acids. Additionally, albumin-based carriers are utilized for anti-tumor drug delivery.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Cell Biology
Xue-Hua Du, Shao-Bo Ke, Xin-Yi Liang, Jie Gao, Xiao-Xiao Xie, Lin-Zhi Qi, Xue-Yi Liu, Guo-Yuan Xu, Xiao-Dong Zhang, Run-Lei Du, Shang-Ze Li
Summary: Our study demonstrates that USP14 functions as a deubiquitinase that interacts and stabilizes JNK, promoting MAPK/JNK signaling and colorectal carcinogenesis. Increased expression of USP14 is associated with elevated levels of JNK protein and downstream gene expression in colorectal cancer patients. Inhibition of USP14 reduces cancer cell proliferation and tumorigenesis by downregulating the activation of the MAPK/JNK pathway.
CELL DEATH & DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Nischal Koirala, Nandini Dey, Jennifer Aske, Pradip De
Summary: HER2 is a cancer-causing driver gene in a subset of breast cancer. Despite the availability of several anti-HER2 targeted therapies, most patients with metastatic HER2+ breast cancer still die from the disease. Cell cycle inhibitors, specifically CDK 4/6 inhibitors, have shown success in managing hormone receptor-positive breast cancer and have the potential for application in HER2+ breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Polymer Science
Patricia Pereira, Armenio C. Serra, Jorge F. J. Coelho
Summary: The use of synthetic polymers as delivery systems for chemotherapy drugs in cancer therapy is a promising field of research due to their unique properties. This review provides an overview of using vinyl polymer-based therapeutic formulations in cancer treatment, discussing potential breakthrough technologies for enhancing efficacy and reducing side effects.
PROGRESS IN POLYMER SCIENCE
(2021)
Article
Oncology
Matthew G. K. Benesch, Rongrong Wu, Xiaoyun Tang, David N. Brindley, Takashi Ishikawa, Kazuaki Takabe
Summary: The lipid phosphate phosphatases (LPPs) are enzymes that regulate signaling in cells. Imbalance of LPP expression levels, with decreased LPP1/3 and increased LPP2, is associated with worse tumor biology, immune system evasion, and decreased survival in breast cancers. Most tumor LPP1/3 is produced by the stroma and LPP2 by cancer cells. Restoring the balance in LPP expression levels, particularly through LPP2 inhibition, could provide adjunct therapies for breast cancer patients.
Article
Oncology
Yuying Fan, Xiaoli Ren, Yingxue Wang, Enshuang Xu, Shuang Wang, Ruidong Ge, Yun Liu
Summary: Metformin was found to induce apoptosis and cell cycle arrest in canine mammary gland tumor cells via the AMPK/AKT/mTOR signaling pathway, suggesting its potential therapeutic effect on CMGTs.
Article
Cell Biology
Cheng Zhou, Juan Du, Liang Zhao, Wei Liu, Tianming Zhao, Hui Liang, Peng Fang, Kaixuan Zhang, Hui Zeng
Summary: The study revealed that overexpression of GLI1 promotes cell proliferation and reduces chemotherapy sensitivity in AML cells, while knocking down GLI1 has the opposite effect. GLI1 directly activates the PI3K/AKT pathway, and inhibitors of GLI1 and CDK4/6 show synergistic effects in promoting drug sensitivity in AML patients.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Chuntao Li, Bo Chen, Junxia Zhang, Jingxuan Yang, Muzi Guo, Yu Ren, Zhijun Zhou, Kar-Ming Fung, Min Li, Liyang Zhang, Zhixiong Liu
Summary: SEM1 is highly expressed in gliomas and correlated with malignant features and poor prognosis. SEM1 plays a critical role in the proliferation, apoptosis, invasion, and migration of glioma cells through regulating the PI3K-Akt pathway. The SEM1 malignant regulatory network shows significant importance for the prognosis and treatment of gliomas.
Article
Cell Biology
Peng Zhang, Liang Chen, Fenfang Zhou, Zhiwen He, Gang Wang, Yongwen Luo
Summary: Prostate cancer (PCa) is a common male malignancy with unclear progression mechanisms. This study found that NRP1, highly expressed in PCa, was associated with poor prognosis in PCa patients. Functionally, NRP1 depletion inhibited PCa cell proliferation and migration, while NRP1 overexpression promoted these processes. Mechanistically, NRP1 was regulated by HIF1 alpha and interacted with EGFR, leading to EGFR phosphorylation and activation of the AKT signaling pathway, promoting PCa progression. Additionally, the NRP1 inhibitor EG01377 inactivated the EGFR/AKT signaling axis and suppressed PCa progression.
CELL DEATH & DISEASE
(2023)
Article
Peripheral Vascular Disease
Diego A. Duarte, Lucas T. Parreiras-e-Silva, Eduardo B. Oliveira, Michel Bouvier, Claudio M. Costa-Neto
Summary: This study investigated the phenomenon of tachyphylaxis in the angiotensin II type 1 receptor (AT(1)R) and found that ligand-binding kinetics play an important role in tachyphylaxis. The endogenous tachyphylactic agonist Ang II had a longer residence time at the receptor compared to analogs, resulting in sustained G(q) protein activation and recruitment of beta-arrestin. Furthermore, Ang II led to sustained receptor internalization, preventing further receptor responses.
Article
Oncology
Eva Ellebaek, Aimilia Schina, Henrik Schmidt, Charlotte Aaquist Haslund, Lars Bastholt, Inge Marie Svane, Marco Donia
Summary: This study found that initiation of immunotherapy in summer is associated with prolonged survival in patients with BRAF wild-type melanoma in Denmark.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Editorial Material
Gastroenterology & Hepatology
Emilie K. Dahl, Osama K. Abed, Jens Kjeldsen, Marco Donia, Inge M. Svane, Anders Dige, Jorgen S. Agnholt, Jacob T. Bjerrum, Jakob B. Seidelin
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Immunology
Qing Li, Jialuo He, Senlin Li, Cheng Tian, Jian Yang, Huimin Yuan, Yi Lu, Paolo Fagone, Ferdinando Nicoletti, Ming Xiang
Summary: Pancreatic cancer (PC) has a cold tumor immune microenvironment (TIME) with minimal dendritic cell (DC) and T cell infiltration, leading to inadequate immunotherapy and chemotherapy. Combining gemcitabine (GEM) with ginsenoside Rh2 (Rh2) can enhance tumor immunogenicity and induce lasting anti-tumor immunity in PC. The activation of DCs by Rh2 via the CARD9-BCL10-MALT1/NF-KB pathway may reverse the cold TIME and optimize GEM chemotherapy, providing a potentially feasible and safe treatment strategy for PC.
CLINICAL IMMUNOLOGY
(2023)
Article
Oncology
Inna M. Chen, Marco Donia, Christopher A. Chamberlain, Agnete W. P. Jensen, Arianna Draghi, Susann Theile, Kasper Madsen, Jane P. Hasselby, Anders Toxvaerd, Estrid Hogdall, Torben Lorentzen, Eva E. Wilken, Poul Geertsen, Inge M. Svane, Julia S. Johansen, Dorte Nielsen
Summary: The combination of ipilimumab, nivolumab, tocilizumab, and SBRT did not meet the expected criteria for treating pancreatic cancer.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Simona Aleksandrova, Ralitza Alexova, Stela Dragomanova, Reni Kalfin, Ferdinando Nicoletti, Paolo Fagone, Maria Cristina Petralia, Katia Mangano, Lyubka Tancheva
Summary: Pomegranate is a polyphenol-rich food and medicinal plant that contains various beneficial compounds. Studies have shown that these compounds can target brain cells and support their functions by regulating redox balance, proliferation, and survival. The neuroprotective effects of pomegranate are mediated by its antioxidant and anti-inflammatory properties, ability to activate signaling pathways, and regulation of mitochondrial damage. In vitro and in vivo studies have demonstrated that pomegranate polyphenols can directly affect neuronal and glial cells, as well as influence blood-brain barrier function and increase blood flow to the brain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Thomas Hach, Kasra Shakeri-Nejad, Marc Bigaud, Frank Dahlke, Massimiliano de Micco, Olivier Petricoul, Gordon Graham, Daniela Piani-Meier, Renato Turrini, Volker Brinkmann, Ferdinando Nicoletti
Summary: Maladjusted immune responses to COVID-19 can lead to immunopathology and acute respiratory distress syndrome. Sphingosine-1-phosphate and its receptors play a crucial role in maintaining endothelial cell chemotaxis and barrier integrity. S1PR modulators can attenuate cytokine release and enhance the pulmonary endothelial barrier. Certain drugs used in multiple sclerosis have shown effectiveness and potential in COVID-19 patients.
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
(2023)
Article
Neurosciences
Nicole Piera Palomba, Giorgio Fortunato, Giuseppe Pepe, Nicola Modugno, Sara Pietracupa, Immacolata Damiano, Giada Mascio, Federica Carrillo, Luca Giovanni Di Giovannantonio, Laura Ianiro, Katiuscia Martinello, Viola Volpato, Vincenzo Desiato, Riccardo Acri, Marianna Storto, Ferdinando Nicoletti, Caleb Webber, Antonio Simeone, Sergio Fucile, Vittorio Maglione, Teresa Esposito
Summary: This study focuses on the common and rare variants identified in the lysosomal K+ channel TMEM175 and their association with Parkinson's disease. Through clinical and genetic analysis, the study identified several common variants and 13 highly penetrant detrimental mutations in the TMEM175 gene. Functional analysis revealed a loss of K+ conductance and impaired autophagic/lysosomal proteolytic flux in patient-derived cells, suggesting a potential role of TMEM175 gene mutations in the pathophysiology of PD.
MOLECULAR NEUROBIOLOGY
(2023)
Letter
Gastroenterology & Hepatology
Emilie Dahl, Osama Abed, Jorgen Agnholt, Jacob Bjerrum, Anders Dige, Jens Kjeldsen, Inge Svane, Marco Donia, Jakob Seidelin
Summary: This article is linked to Dahl et al papers. To view these articles, visit...
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Oncology
Tine J. Monberg, Troels H. Borch, Inge M. Svane, Marco Donia
Summary: Treatment with tumor-infiltrating lymphocytes (TIL) has been proven to be safe, feasible, and effective for patients with metastatic melanoma. However, its implementation on a larger scale is currently limited due to the lack of regulatory approvals. This review discusses the current knowledge of TIL therapy and addresses the practical, logistic, and economic challenges associated with its widespread implementation.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Arianna Draghi, Mario Presti, Agnete W. P. Jensen, Christopher A. Chamberlain, Benedetta Albieri, Anne-Christine K. Rasmussen, Mads H. Andersen, Michael D. Crowther, Inge Marie Svane, Marco Donia
Summary: Our study demonstrates that exploiting tumor-specific cytotoxic CD4(+) TILs could help overcome resistance to ICB mediated by IFN gamma-signaling loss in MHCIIconst(+) melanomas.
CLINICAL CANCER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Ralitza Alexova, Simona Alexandrova, Stela Dragomanova, Reni Kalfin, Ayten Solak, Sidharth Mehan, Maria Cristina Petralia, Paolo Fagone, Katia Mangano, Ferdinando Nicoletti, Lyubka Tancheva
Summary: Pomegranate is a rich source of polyphenols that have anti-inflammatory and antioxidant activity, and can support the immune system during viral infection and recovery. Studies have shown that pomegranate polyphenol extract and its components can control immune cell infiltration, regulate cytokine secretion, inhibit viruses like SARS-CoV-2, and modulate the NF-κB pathway. Further research is needed to understand the interactions between polyphenols, viruses, and the host immune response.
Review
Pharmacology & Pharmacy
Gian Marco Leone, Saverio Candido, Alessandro Lavoro, Silvia Vivarelli, Giuseppe Gattuso, Daniela Calina, Massimo Libra, Luca Falzone
Summary: Lung cancer is the second most diagnosed tumor with the highest mortality rate. Recent progress in the treatment of lung cancer includes targeted therapies and immunotherapy, which have been approved in clinical practice. This review discusses the current and ongoing clinical studies on targeted therapies and immune-checkpoint inhibitors for lung cancer, as well as the advantages and limitations of these new therapeutic approaches. Furthermore, the importance of human microbiota as biomarkers and therapeutic targets for lung cancer is analyzed. The future research milestones in personalized treatment for lung cancer are expected to consider the genetic landscape, immune background, and individual variables such as patient-specific gut microbial composition.
Article
Biochemistry & Molecular Biology
Garry Dolton, Cristina Rius, Aaron Wall, Barbara Szomolay, Valentina Bianchi, Sarah A. E. Galloway, Md Samiul Hasan, Theo Morin, Marine E. Caillaud, Hannah L. Thomas, Sarah Theaker, Li Rong Tan, Anna Fuller, Katie Topley, Mateusz Legut, Meriem Attaf, Jade R. Hopkins, Enas Behiry, Joanna Zabkiewicz, Caroline Alvares, Angharad Lloyd, Amber Rogers, Peter Henley, Christopher Fegan, Oliver Ottmann, Stephen Man, Michael D. Crowther, Marco Donia, Inge Marie Svane, David K. Cole, Paul E. Brown, Pierre Rizkallah, Andrew K. Sewell
Summary: Tumor-infiltrating lymphocyte therapy can activate T cells of the immune system to target and eliminate solid cancers. Through the use of combinatorial peptide libraries and a proteomic database, the antigen specificities of persistent cancer-specific T cell receptors (TCRs) were identified after successful therapy for stage IV malignant melanoma. These TCRs were capable of targeting multiple tumor types through specific epitopes, and the atomic structures revealed the importance of a shared recognition motif. The ability of these multi-epitope targeting T cells to recognize cancer cells surpasses the recognition of individual epitopes, making them promising candidates for future immunotherapies.
Article
Neurosciences
Ferdinando Nicoletti, Luisa Di Menna, Luisa Iacovelli, Rosamaria Orlando, Anna Rita Zuena, P. Jeffrey Conn, Shalini Dogra, Max E. Joffe
Summary: Cellular responses to metabotropic glutamate (mGlu) receptor activation are influenced by mechanisms of receptor-receptor interaction, including receptor dimerization and complex formation with other GPCRs. The interactions between different mGlu receptor subtypes and other receptors have been studied in various brain regions and have been implicated in the pathophysiology of several neurological and psychiatric disorders. Understanding these interactions could lead to the development of new therapeutic targets for these conditions.
Article
Neurosciences
Luisa Di Menna, Rosamaria Orlando, Giovanna 'Errico, Roxana Paula Ginerete, Agata Machaczka, Carmela Maria Bonaccorso, Andrea Arena, Michela Spatuzza, Roberta Celli, Marika Alborghetti, Eleonora Ciocca, Anna Rita Zuena, Mariarosaria Scioli, Valeria Bruno, Giuseppe Battaglia, Ferdinando Nicoletti, Maria Vincenza Catania
Summary: The involvement of mGlu5 receptors in monogenic autism has been supported by various studies, but there is a lack of research on the canonical signal transduction pathway activated by these receptors in mouse models of autism. In this study, we developed a method to assess PI hydrolysis in vivo and found that mGlu5 receptor-mediated PI hydrolysis was impaired in different brain regions of mice modeling Angelman syndrome and fragile-X syndrome. These findings provide the first evidence that the canonical transduction pathway of mGlu5 receptors is downregulated in mouse models of monogenic autism.