Article
Chemistry, Multidisciplinary
Melanie Donnette, Mourad Hamimed, Joseph Ciccolini, Yael Berda-Haddad, Elise Kaspi, Geoffroy Venton, Bruno Lacarelle, Regis Costello, L''Houcine Ouafik, Laure Farnault, Raphaelle Fanciullino
Summary: The pharmacokinetics of liposomal CPX-351 in treating AML patients were studied, revealing a major impact of CDA status on cytarabine PK and safety.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Pharmacology & Pharmacy
Mingtan Tang, Lina Lozano Hernandez, Joy N. Reginald-Opara, Darren Svirskis, Euphemia Leung, Hongbo Wang, Zimei Wu
Summary: This study investigated the potential of using zebularine in combination with a nanomedicine co-delivery approach to overcome gemcitabine-resistance in pancreatic cancer cells. Zebularine was found to suppress the regrowth of senescent cells and enhance cellular gemcitabine concentration. Co-delivery of zebularine with liposomes increased cellular gemcitabine concentration and extended the half-life of gemcitabine in plasma.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Qian Jia, Hui Zeng, Huanxi Li, Nan Xiao, Jing Tang, Shangfang Gao, Jinbing Zhang, Wei Xie
Summary: In this study, the researchers determined the structures of GSDA in plants, revealing its catalytic mechanism and structural rearrangements during reactions. The identification of additional substrates and comparison with other deaminases helped uncover recognition differences for specific substrates. These findings may contribute to the development of deaminase-based gene-editing tools.
CHEMICAL COMMUNICATIONS
(2021)
Article
Oncology
Sarrah L. Hasanali, Daley S. Morera, Ronny R. Racine, Martin Hennig, Santu Ghosh, Luis E. Lopez, Marie C. Hupe, Diogo O. Escudero, Jiaojiao Wang, Huabin Zhu, Semih Sarcan, Ijeoma Azih, Michael Zhou, Andre R. Jordan, Martha K. Terris, Markus A. Kuczyk, Axel S. Merseburger, Vinata B. Lokeshwar
Summary: This study identified that the splice variant V1 of HYAL-4 is upregulated in bladder cancer and drives a malignant phenotype, as well as chemotherapy resistance to gemcitabine. While V1 does not affect gemcitabine influx, it increases drug metabolism and efflux by upregulating CD44-JAK2/STAT3 signaling, leading to resistance.
CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Abby M. Green, Rachel A. DeWeerd, David R. O'Leary, Ava R. Hansen, Katharina E. Hayer, Katarzyna Kulej, Ariel S. Dineen, Julia H. Szeto, Benjamin A. Garcia, Matthew D. Weitzman
Summary: APOBEC3 enzymes, particularly A3A, are implicated in causing somatic mutations in cancer genomes. A3A interacts with the CCT complex, disrupting CCT function and leading to increased mutational activity. Silencing mutations in CCT subunit genes in cancer genomes are associated with enrichment of A3A mutational signatures.
Article
Oncology
Lili Hu, Xintong Mao, Chao Gao, Yinhai Xu, Chenglin Li, Tao Wang, Dongmei Lv
Summary: The study found that Chinese non-small-cell lung cancer patients carrying the CDA 435C/T or T/T genotypes have better efficacy with gemcitabine-platinum treatment but are more prone to leukopenia.
Article
Microbiology
Feixuan Li, Xiao-Yu Liu, Lei Ni, Fan Jin
Summary: Researchers developed a method called AIDmut-Seq to detect transcription factor targets on the genome. It involves simple steps and has been validated for various transcriptional activators. However, it has lower efficiency for some small transcriptional repressors. Despite potential false-positive and false-negative results, AIDmut-Seq shows promise as a complementary tool for studying protein-DNA interactions.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biotechnology & Applied Microbiology
Jie Wang, Dongdong Zhao, Ju Li, Muzi Hu, Xiuqing Xin, Marcus A. Price, Qingyan Li, Li Liu, Siwei Li, Susan J. Rosser, Chunzhi Zhang, Changhao Bi, Xueli Zhang
Summary: This study demonstrates the use of CRISPR-enabled deaminase base editing to precisely edit nucleotides on the chromosome using DNA helicases fused with activation-induced cytidine deaminase. The coordinated editing process with DNA replication resulted in increased production of 8-carotene. Furthermore, the technique of fusing AID with eukaryotic helicase could potentially be applied for various applications in eukaryotic cells.
METABOLIC ENGINEERING
(2021)
Article
Microbiology
Zhiwei Hu, Yannan Wang, Qian Liu, Yan Qiu, Zhiyu Zhong, Kangdi Li, Wenhua Li, Zixin Deng, Yuhui Sun
Summary: This study introduces a novel approach using bubble hairpin single guide RNAs (BH-sgRNAs) to significantly reduce off-target editing and improve the purity of on-target editing in base editors. This design represents a major improvement in the specificity of base editing tools.
Article
Biochemical Research Methods
Guiyue Tang, Bingran Xie, Xiangna Hong, Hang Qin, Jingfang Wang, Hai Huang, Pei Hao, Xuan Li
Summary: The study successfully separated the dual activities of A3A and created novel human A3A variants with RNA-specific cytidine deaminase activity through the development of a reporter system and rational mutagenesis design.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Fisheries
Yujie Liu, Kefan Xing, Zixuan Wu, Congcong Yan, Yuying Sun, Jiquan Zhang
Summary: Economic crustaceans play important roles in aquaculture, and their genomic single nucleotide polymorphism (SNP) sites are closely related to various life activities. However, the functional study of SNPs in crustaceans still lacks appropriate techniques. In this study, a cytidine base editor (CBE) based on cytidine deaminase (CDA) was constructed for crustacean point editing. The editing efficiency was validated in the target gene of Neocaridina denticulata sinensis, achieving a conversion of C·G to T·A with an efficiency of approximately 11.21%. This work establishes a well-established crustacean base editing platform.
AQUACULTURE REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Luis Vergara-Gomez, Carolina Bizama, Jun Zhong, Kurt Buchegger, Felipe Suarez, Lorena Rosa, Carmen Ili, Helga Weber, Javiera Obreque, Karena Espinoza, Gabriela Repetto, Juan C. Roa, Pamela Leal, Patricia Garcia
Summary: This study investigated the molecular mechanisms of acquired resistance in gallbladder cancer by developing and characterizing gemcitabine-resistant cell lines. Transcriptome profiling and phosphotyrosine proteomic analyses revealed dysregulated biological processes and signaling pathways, as well as potential therapeutic targets in gallbladder cancer. The findings greatly enhance our understanding of acquired drug resistance in gallbladder cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Genetics & Heredity
Tony M. Mertz, Christopher D. Collins, Madeline Dennis, Margo Coxon, Steven A. Roberts
Summary: The occurrence and development of cancer are closely related to mutations, and dysregulated activity of APOBECs can lead to mutations. The study of mutation signatures helps us understand the patterns and processes of mutations. In humans, APOBEC-generated genetic heterogeneity plays an important role in cancer development, metastasis, and resistance to therapy.
ANNUAL REVIEW OF GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Xia Xie, Tingting Gan, Bing Rao, Weiwei Zhang, Rohit A. Panchakshari, Dingpeng Yang, Xiong Ji, Yu Cao, Frederick W. Alt, Fei-Long Meng, Jiazhi Hu
Summary: The mutant AID-delC protein fails to efficiently target antibody genes, forms condensates, and may exert a dominant-negative effect on wild-type AID.
Article
Immunology
Rodolphe Suspene, Kyle A. Raymond, Laetitia Boutin, Sophie Guillier, Frederic Lemoine, Olivier Ferraris, Jean-Nicolas Tournier, Frederic Iseni, Etienne Simon-Loriere, Jean-Pierre Vartanian
Summary: We analyzed the level of APOBEC3-induced MPXV editing in infected cells and in patients. We demonstrated that G->A hypermutated MPXV genomes can be recovered from APOBEC3F transfection followed by MPXV infection. Hyperedited genomes were also recovered in similar to 42% of patients.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Review
Biochemistry & Molecular Biology
Marika Franczak, Isabel Toenshoff, Gerrit Jansen, Ryszard T. Smolenski, Elisa Giovannetti, Godefridus J. Peters
Summary: Mitochondria are crucial for cancer cells as they play a significant role in their energy requirements and chemoresistance. Differences in energy metabolism, such as higher NAD(+) levels, the Warburg effect, and increased one-carbon metabolism, have been identified between cancer and normal cells. Targeting these metabolic pathways could be a promising approach for developing new anticancer drugs. Combining novel drugs with conventional agents may provide effective treatments for cancer.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Motahareh Mortazavi, Elaheh Raufi, Tahereh Damghani, Mehdi Khoshneviszadeh, Najmeh Edraki, Masoomeh Eskandari, Elisa Giovannetti, Godefridus J. Peters, Somayeh Pirhadi, Omidreza Firuzi
Summary: c-Met receptor tyrosine kinase is an important therapeutic target in pancreatic cancer. A virtual screening and experimental testing were conducted to identify potential c-Met inhibitors from a compound library. The most active compound, PhTH, demonstrated antiproliferative effects against PDAC cells, induced apoptosis, and inhibited c-Met activity. Molecular docking and simulation analysis confirmed the strong interactions between PhTH and c-Met kinase domain. These findings suggest the potential of PhTH and other compounds as c-Met inhibitors in the treatment of PDAC.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Oncology
M. Houweling, U. K. Abdul, C. Brahm, T. Lagerweij, S. Heukelom, P. W. Koken, R. Honeywell, L. E. Wedekind, G. J. Peters, H. Verheul, P. Sminia, D. Noske, T. Wurdinger, B. A. Westerman
Summary: This study investigated the radio-sensitizing effect of MEK inhibitor PD0325901 in in vitro and in vivo models of glioblastoma (GBM). The results showed that both MEK inhibitors had an in vitro radio-sensitizing effect, but no significant interaction between PD0325901 MEK inhibition and irradiation was observed in in vivo experiments.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
Alessandro Gregori, Cecilia Bergonzini, Mjriam Capula, Giulia Mantini, Fatemeh Khojasteh-Leylakoohi, Annalisa Comandatore, Ghazaleh Khalili-Tanha, Alireza Khooei, Luca Morelli, Amir Avan, Erik H. Danen, Thomas Schmidt, Elisa Giovannetti
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and chemoresistant cancer, with a stiff stroma surrounding it playing a role in chemoresistance. High expression of the mechanical sensor ITGA2 correlated with a poor prognosis in PDAC patients, and increased matrix stiffness led to the expression of ITGA2 and chemoresistance to gemcitabine. ITGA2 could be a potential therapeutic target to overcome gemcitabine resistance.
Review
Oncology
Marie-Christine Etienne-Grimaldi, Nicolas Pallet, Valerie Boige, Joseph Ciccolini, Laurent Chouchana, Chantal Barin-Le Guellec, Aziz Zaanan, Celine Narjoz, Julien Taieb, Fabienne Thomas, Marie-Anne Loriot
Summary: Fluoropyrimidine drugs are commonly used in chemotherapy for solid tumors, and deficiency in the enzyme DPD can lead to severe toxicity. This review explores the pharmacogenetics and therapeutic recommendations for genotyping and phenotyping DPD to prevent toxicity and optimize dosing adaptation. The mandatory screening for DPD deficiency in France is also discussed.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Federica Borea, Marika A. Franczak, Maria Garcia, Matteo Perrino, Nadia Cordua, Ryszard T. Smolenski, Godefridus J. Peters, Rafal Dziadziuszko, Armando Santoro, Paolo A. Zucali, Elisa Giovannetti
Summary: Malignant Pleural Mesothelioma (MPM) is a rare neoplasm that is usually diagnosed at an advanced stage and requires systemic treatment due to its ineligibility for radical surgery. Chemotherapy has been the standard treatment for 20 years until immune checkpoint inhibitors were introduced. However, the prognosis remains poor, and targeted therapies for MPM have mostly failed in clinical trials. This review aims to explore the potential reasons for treatment failures and determine the need for further research in this area.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marika A. Franczak, Oliwia Krol, Gabriela Harasim, Agata Jedrzejewska, Nadia Zaffaroni, Carlotta Granchi, Filippo Minutolo, Amir Avan, Elisa Giovannetti, Ryszard T. Smolenski, Godefridus J. Peters
Summary: Malignant mesothelioma (MM) is a highly aggressive and resistant tumor. In this study, the cytotoxicity of new inhibitors of glucose transporter type 1 (GLUT-1) and lactate dehydrogenase-A (LDH-A) in relation to ATP/NAD+ metabolism, glycolysis and mitochondrial respiration was investigated. The inhibitors showed cytotoxicity in MM cells, associated with a decrease in ATP and NAD+, and were most effective in cells with the highest metabolic modulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Mahrou Vahabi, Bilal Dehni, Ines Antomas, Elisa Giovannetti, Godefridus J. Peters
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited improvement in mortality rate despite extensive research and clinical trials. There is a need for comprehensive molecular characterization to identify biomarkers for early detection and evaluation of treatment response. MicroRNAs (miRNAs) show promise as stable biomarkers that can be detected in fixed tissues and biofluids, and their deregulation plays a role in the oncogenesis and metastasis of PDAC. Several oncomiRs and TsmiRs have been identified that contribute to chemoresistance in PDAC, and miRNA-based therapy approaches have shown success in vivo. Integrating miRNAs in PDAC treatment holds potential for personalized medicine.
CANCER AND METASTASIS REVIEWS
(2023)
Article
Oncology
Yan Zhou, Yizhen Guo, Maoxin Ran, Wenying Shan, Carlotta Granchi, Elisa Giovannetti, Filippo Minutolo, Godefridus J. Peters, Kin Yip Tam
Summary: This study investigated the anticancer effects of combined inhibition of PDK1 and LDHA in LUAD and its underlying mechanisms. The results showed that the combination of a PDK1 inhibitor and a LDHA inhibitor could synergistically inhibit LUAD growth and suppress tumor growth in vivo. This combination also inhibited cellular migration and colony formation, inducing mitochondrial depolarization and apoptosis in LUAD cells.
Letter
Oncology
Lenka N. C. Boyd, Mahsoem Ali, Jisce R. Puik, Laura L. Meijer, Tessa Y. S. Le Large, Hanneke W. M. van Laarhoven, Elisa Giovannetti, Geert Kazemier
CLINICAL CANCER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Mahrou Vahabi, Annalisa Comandatore, Marika A. Franczak, Ryszard T. Smolenski, Godefridus J. Peters, Luca Morelli, Elisa Giovannetti
Summary: Exosomes play a crucial role in intercellular communication and can influence cancer cell behavior and response to treatment. They can transport glycolytic enzymes, leading to altered glucose metabolism and increased tumor progression, survival, immune evasion, and drug resistance. Understanding exosome-mediated cell-to-cell communication may open new therapeutic avenues and facilitate biomarker development, and combining exosome-based-targeted therapies with existing treatments holds promise in overcoming resistance and improving cancer treatment outcomes.
CYTOKINE & GROWTH FACTOR REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Lars Petter Jordheim, Caius G. Radu, Godefridus J. Peters
Summary: This article introduces the scientific program of the 20th biennial symposium on Purine and Pyrimidine metabolism organized by the Purine and Pyrimidine Society (PPS) in June 2023. The symposium covers various topics including inborn errors, cancer, immunity, enzymatic reactions, and drug development, and is presented in 9 sessions over three days.
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
(2023)
Article
Biochemistry & Molecular Biology
Nabeel Merali, Tarak Chouari, Julien Terroire, Maria-Danae Jessel, Daniel S. K. Liu, James-Halle Smith, Tyler Wooldridge, Tony Dhillon, Jose I. Jimenez, Jonathan Krell, Keith J. Roberts, Timothy A. Rockall, Eirini Velliou, Shivan Sivakumar, Elisa Giovannetti, Ayse Demirkan, Nicola E. Annels, Adam E. Frampton
Summary: The bile microbiome plays an important role in pancreatic ductal adenocarcinoma (PDAC) and can distinguish malignant tumors from benign ones. It was found that the composition of the bile microbiome is altered in patients with PDAC, suggesting that these microbial changes could potentially serve as diagnostic and prognostic biomarkers for PDAC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Mourad Hamimed, Raynier Devillier, Pierre-Jean Weiller, Clemence Marin, Jean-Marc Schiano, Nawel Belmecheri, Marie-Christine Etienne-Grimaldi, Joseph Ciccolini, Samia Harbi
Summary: We report a case of an adult patient with Hodgkin's lymphoma who experienced severe toxicities after Pembrolizumab treatment, suggesting impaired elimination of the drug.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2023)
