Article
Oncology
Juan M. Roldan-Romero, Carlos Valdivia, Maria Santos, Javier Lanillos, Pablo Maroto, Georgia Anguera, Bruna Calsina, Angel Martinez-Montes, Maria Monteagudo, Sara Mellid, Luis J. Leandro-Garcia, Cristina Montero-Conde, Alberto Cascon, Giovanna Roncador, Javier Coloma, Mercedes Robledo, Cristina Rodriguez-Antona
Summary: Mammalian target of rapamycin (mTOR) is an attractive target for cancer therapy due to its role in promoting tumor growth and resistance to chemotherapy. Whole exome sequencing of chromophobe renal cell carcinoma (chRCC) patients with exceptional mTOR inhibitor sensitivity revealed somatic mutations in the deubiquitinase gene USP9X. By studying multiple patients' samples, it was confirmed that USP9X plays a role in sensitivity to mTOR inhibitors by affecting autophagy and the p62 pathway. These findings suggest that USP9X could serve as a potential marker and strategy for increasing sensitivity to mTOR inhibitors in chRCC patients.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Cell Biology
Qiujie Wang, Cheng Bin, Qiang Xue, Qingzhu Gao, Ailong Huang, Kai Wang, Ni Tang
Summary: The study revealed that GSTZ1 enhances sorafenib-induced ferroptosis by inhibiting the NRF2/GPX4 axis in HCC cells, and the combination therapy of sorafenib and GPX4 inhibitor RSL3 may be a promising strategy in HCC treatment.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Rindert Missiaen, Nicole M. Anderson, Laura C. Kim, Bailey Nance, Michelle Burrows, Nicolas Skuli, Madeleine Carens, Romain Riscal, An Steensels, Fuming Li, M. Celeste Simon
Summary: Hepatocellular carcinoma (HCC) depends on exogenous arginine due to repression of urea cycle gene expression and unique dependence on cationic amino acid transporter SLC7A1. Arginine deprivation induces an integrated stress response, leading to HCC cell-cycle arrest and quiescence. Inhibiting GCN2 in arginine-deprived HCC cells promotes a senescent phenotype, making these cells vulnerable to senolytic compounds. Combined dietary arginine deprivation, GCN2 inhibition, and senotherapy show potential for HCC treatment.
Article
Medicine, General & Internal
Ritu Shrestha, Prashanth Prithviraj, Kim R. Bridle, Darrell H. G. Crawford, Aparna Jayachandran
Summary: Hepatocellular carcinoma (HCC) is a common malignancy, and treatment with Sorafenib may lead to drug resistance. Research shows that combining inhibition of EMT and immune checkpoint molecules can enhance the sensitivity of HCC cells to Sorafenib.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Deguo Zhang, Da Man, Jiahua Lu, Yifan Jiang, Bo Ding, Rong Su, Rongliang Tong, Junru Chen, Beng Yang, Shusen Zheng, Diyu Chen, Jian Wu
Summary: This study investigates the role of mitochondrial translocator protein (TSPO) in the regulation of ferroptosis and antitumor immunity in hepatocellular carcinoma (HCC). The results show that TSPO promotes HCC cell growth, migration, and invasion, and inhibits ferroptosis through enhancing the Nrf2-dependent antioxidant defense system. Furthermore, TSPO upregulates PD-L1 expression and promotes HCC immune escape. Targeting TSPO can be a promising new strategy for HCC treatment.
Article
Environmental Sciences
Feibo Xu, Yanfei Li, Zheng Cao, Jian Zhang, Wanyue Huang
Summary: Aflatoxin B1 (AFB1) contaminates foodstuffs and feeds, causing liver injury and mitochondrial dysfunction, which triggers mitochondria-dependent apoptosis and ultimately induces hepatic lesions.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Oncology
Antonio Mulero-Sanchez, Christel F. A. Ramirez, Aimee du Chatinier, Hui Wang, Sofie J. I. Koomen, Ji-Ying Song, Marnix H. P. de Groot, Cor Lieftink, Astrid Bosma, Artur Burylo, Olaf van Tellingen, Roderick L. Beijersbergen, Cun Wang, Leila Akkari, Rene Bernards, Sara Mainardi
Summary: Liver cancer is a major cause of cancer-related death globally, with limited therapeutic options available. Reactivation of receptor tyrosine kinases (RTK) has been identified as a mechanism of resistance to targeted therapies in various cancers. In this study, we demonstrate that multiple RTK are activated upon mTOR inhibition in hepatocellular carcinoma (HCC), leading to reactivation of the mTOR pathway. Co-inhibition of mTOR and SHP2, a downstream target of RTK, synergistically induces apoptosis and effectively impairs tumor growth in HCC mouse models. These findings suggest a novel rational combination therapy for HCC.
MOLECULAR ONCOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Wei Zhou, Weiyang Lou, Junru Chen, Bisha Ding, Binjie Chen, Haiyang Xie, Lin Zhou, Shusen Zheng, Donghai Jiang
Summary: The study demonstrated that sub-toxic AG-1024 can significantly enhance the sensitivity of HCC cells to sorafenib, potentially serving as a promising therapeutic agent for HCC patients refractory to sorafenib treatment. It was found that sub-toxic AG-1024 combined with sorafenib exerted synergistic anti-cancer effects by enhancing cell inhibition and G1/S arrest while having less impact on apoptosis, which could be a key mechanism for overcoming sorafenib resistance in HCC cells.
ONCOTARGETS AND THERAPY
(2021)
Article
Oncology
Lingli Huang, Di Xiao, Tianyu Wu, Xin Hu, Jun Deng, Xinjian Yan, Jingtao Wu, Simeng Xu, Xiaoping Yang, Gaofeng Li
Summary: The combination of phenformin and sorafenib demonstrates synergistic effects in suppressing HCC cell proliferation, migration, and survival, while enhancing the inhibition of the CRAF/ERK and PI3K/AKT/mTOR pathways. This combination also shows better efficacy in murine models without significant toxicity, suggesting potential promise in treating hepatocellular carcinoma.
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
(2021)
Article
Plant Sciences
Li-Juan Deng, Yu-He Lei, Jing-Yu Quan, Bao-Jing Li, Dong-Mei Zhang, Hai-Yan Tian, Ye Chen, En-Xin Zhang, Lei Chen, Wen-Cai Ye, Wei-Min Ning, Lin-Zhong Yu, Jun-Shan Liu
Summary: This study evaluated the anti-hepatoma activity of 1 beta-OH-ABF against liver cancer cells in vitro and in vivo, and explored the underlying mechanisms. Results showed that 1 beta-OH-ABF induces mitochondrial apoptosis through the suppression of mTOR signaling in vitro and in vivo, suggesting its potential as a treatment for liver cancer.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Environmental Sciences
Haiyan Yu, Zhiwei Hao, Xuemin Liu, Zhixuan Wei, Renming Tan, Xiaotian Liu, Qiongxia Chen, Ying Chen, Hongyan Zhou, Yuchen Liu, Zhengqi Fu
Summary: This study aimed to investigate the role of autophagy in DAS-induced growth inhibition of HepG2 and Huh7 hepatocellular carcinoma cells. We found that DAS treatment activated the AMPK/mTOR pathway and inhibited autophagic flux through blocking the fusion of autophagosomes with lysosomes. DAS also increased lysosomal pH and inhibited Cathepsin D maturation. Co-treatment with an autophagy inhibitor further enhanced the growth inhibitory activity of DAS in HCC cells.
ENVIRONMENTAL TOXICOLOGY
(2023)
Article
Oncology
Qingyi Zhang, Xu Lin, Kan Jiang, Jun Deng, Lei Ke, Ziheng Wu, Pinghui Xia, Qi Li, Li Yu, Pengzhi Ni, Wang Lv, Jian Hu
Summary: In this study, PD0166285 was found to inhibit the growth of ESCC cells, induce cell apoptosis, and enhance the sensitivity of ESCC cells to radiotherapy. Furthermore, PD0166285 attenuated DNA damage repair by inhibiting Rad51. These findings suggest that PD0166285 could be a potential therapeutic option for ESCC in the future.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Di Liu, Junhao Liu, Kejun Liu, Yanchao Hu, Jinming Feng, Yang Bu, Qi Wang
Summary: SIRT1 is upregulated in hepatocellular carcinoma (HCC) and negatively correlates with GSDME-N. Silencing of SIRT1 inhibits proliferation, migration, and invasion of HCC cells while promoting apoptosis and inducing mitochondrial damage. Inhibition of GSDME reduces SIRT1 silencing-induced cell swelling, decreases lactate dehydrogenase (LDH) release, and promotes apoptosis in HCC cells.
MOLECULAR BIOTECHNOLOGY
(2023)
Article
Oncology
Kubra Narci, Deniz Cansen Kahraman, Altay Koyas, Tulin Ersahin, Nurcan Tuncbag, Rengul Cetin Atalay
Summary: This study investigated the differential effects of isoform specific PI3K inhibitors in combination with Sorafenib on liver cancer cells, demonstrating distinct consequences of PIK-75 and TGX-221 in different cellular contexts. The analysis using PCST revealed the mechanisms behind these differences, highlighting the importance of context dependent and isoform specific PI3K/Akt/mTOR signaling inhibition in drug resistance during combination therapies.
Article
Oncology
Alvaro Quintanal-Villalonga, Hirokazu Taniguchi, Yuan Hao, Andrew Chow, Yingqian A. Zhan, Shweta S. Chavan, Fathema Uddin, Viola Allaj, Parvathy Manoj, Nisargbhai S. Shah, Joseph M. Chan, Michael Offin, Metamia Ciampricotti, Jordana Ray-Kirton, Jacklynn Egger, Umesh Bhanot, Irina Linkov, Marina Asher, Michael H. Roehrl, Juan Qiu, Elisa de Stanchina, Travis J. Hollmann, Richard P. Koche, Triparna Sen, John T. Poirier, Charles M. Rudin
Summary: This study identified XPO1 as a therapeutic target in SCLC through CRISPR-Cas9 screening, and found that inhibition of XPO1 enhances the efficacy of chemotherapy. This discovery provides a new opportunity for the treatment of SCLC.
Article
Chemistry, Medicinal
Elisabeth Bou-Petit, Stefan Hummer, Helena Alarcon, Konstantin Slobodnyuk, Marta Cano-Galietero, Pedro Fuentes, Pedro J. Guijarro, Maria Jose Munoz, Leticia Suarez-Cabrera, Anna Santamaria, Roger Estrada-Tejedor, Jose Borrell, Santiago Ramon y Cajal
Summary: Targeting the kinases MNK1 and MNK2 has emerged as a valuable strategy in oncology. Through rational design, a novel core for MNK inhibitors has been identified and validated, which can affect tumor cell growth without impacting normal cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Joan Frigola, Caterina Carbonell, Patricia Irazno, Nuria Pardo, Ana Callejo, Susana Cedres, Alex Martinez-Marti, Alejandro Navarro, Mireia Soleda, Jose Jimenez, Javier Hernandez-Losa, Ana Vivancos, Enriqueta Felip, Ramon Amat
Summary: Somatic copy number alterations (SCNAs) burden may be a potential biomarker of benefit to immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC), although there are some nuances to consider. Further studies are needed to establish its role as a biomarker of benefit to ICIs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Medicine, General & Internal
Jordi Temprana-Salvador, Pablo Lopez-Garcia, Josep Castellvi Vives, Lluis de Haro, Eudald Ballesta, Matias Rojas Abusleme, Miquel Arrufat, Ferran Marques, Josep R. Casas, Carlos Gallego, Laura Pons, Jose Luis Mate, Pedro Luis Fernandez, Eugeni Lopez-Bonet, Ramon Bosch, Salome Martinez, Santiago Ramon y Cajal, Xavier Matias-Guiu
Summary: Complete digital pathology transformation is challenging yet rewarding for primary histopathological diagnosis. The Catalan Health Institute aims to deploy digital pathology in a comprehensive network to increase patient safety and improve diagnosis and efficiency.
Review
Biochemistry & Molecular Biology
Raul Ventura, Inma Martinez-Ruiz, Maria Isabel Hernandez-Alvarez
Summary: Phospholipids are essential components of eukaryotic membranes and play a crucial role in cell organelles. The synthesis and transport of phospholipids are important for maintaining cellular functions, and their dysfunction can lead to various diseases.
Article
Immunology
Angela Callejo, Maria del Mar Molina, Maria Carme Dinares, Javier Hernandez-Losa, Bibiana Planas, Jorge Garcia, Adria Curran, Jordi Navarro, Paula Suanzes, Vicenc Falco, Joaquin Burgos
Summary: The prevalence of oral HPV infections, abnormal cytology, and lesions in HIV-infected MSM was low, and their correlation with anal HPV-related lesions was slight.
Article
Oncology
Elena Arconada-Luque, Jaime Jimenez-Suarez, Raquel Pascual-Serra, Syong Hyun Nam-Cha, Teresa Moline, Francisco J. Cimas, German Fliquete, Marta Ortega-Muelas, Olga Roche, Diego M. Fernandez-Aroca, Raul Munoz Velasco, Natalia Garcia-Flores, Cristina Garnes-Garcia, Adrian Sanchez-Fdez, Sofia Matilla-Almazan, Victor J. Sanchez-Arevalo Lobo, Javier Hernandez-Losa, Borja Belandia, Atanasio Pandiella, Azucena Esparis-Ogando, Santiago Ramon y Cajal, Luis del Peso, Ricardo Sanchez-Prieto, Maria Jose Ruiz-Hidalgo
Summary: ERK5 plays a critical role in the biology of soft tissue sarcoma, as shown in both mouse models and human sarcomas. Transcriptome analysis reveals the important role of KLF2 in the biological effects of ERK5. These findings open new avenues for the diagnosis and therapy of soft tissue sarcomas.
Article
Biochemistry & Molecular Biology
Fernando Carton-Garcia, Bruno Brotons, Estefania Anguita, Higinio Dopeso, Jordi Tarragona, Rocio Nieto, Elia Garcia-Vidal, Irati Macaya, Zsuzsanna Zagyva, Mariona Dalmau, Manuel Sanchez-Martin, Sven C. D. van Ijzendoorn, Stefania Landolfi, Javier Hernandez-Losa, Simo Schwartz Jr, Xavier Matias-Guiu, Santiago Ramon y Cajal, Agueda Martinez-Barriocanal, Diego Arango
Summary: Loss of myosin Vb reduces polarization/differentiation of colon cancer cells while enhancing their metastatic potential, demonstrating a tumor suppressor function for this myosin. Reduced expression of myosin Vb in tumors identifies a subset of poor prognosis colorectal cancer patients.
Article
Multidisciplinary Sciences
Julie Earl, Silvia Calabuig-Farinas, Maria Eugenia Sarasquete, Laura Muinelo Romay, Sara Lopez-Tarruella, Beatriz Bellosillo Paricio, Marta Rodriguez, Karmele Valencia Leoz, Marta Duenas Porto, Noelia Tarazona, Javier Hernandez Losa, Rodrigo Almeida Toledo
Summary: Liquid biopsy is a diagnostic method based on molecules in blood and other bodily fluids, providing a minimally invasive alternative to solid biopsy while allowing real-time monitoring of tumors. Its applications include early cancer detection, disease progression follow-up, minimal residual disease assessment, and identification of molecular progression and resistance mechanisms. Proper preanalytical procedures such as sample collection, quality, and storage are crucial for reliable analysis.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Biochemistry & Molecular Biology
Elena Elez, Nuria Mulet-Margalef, Miriam Sanso, Fiorella Ruiz-Pace, Francesco M. Mancuso, Raquel Comas, Javier Ros, Guillem Argiles, Giulia Martini, Enrique Sanz-Garcia, Iosune Baraibar, Francesc Salva, Alba Noguerido, Jose Luis Cuadra-Urteaga, Roberta Fasani, Ariadna Garcia, Jose Jimenez, Susana Aguilar, Stefania Landolfi, Javier Hernandez-Losa, Irene Brana, Paolo Nuciforo, Rodrigo Dienstmann, Josep Tabernero, Ramon Salazar, Ana Vivancos
Summary: In this study, the search for immunotherapy biomarkers in Microsatellite Instability High/Deficient Mismatch Repair system (MSI-H/dMMR) metastatic colorectal cancer (mCRC) was conducted. Different gene mutations were found to be more frequent in patients with resistance to PD-1/PD-L1 inhibitors compared to those with response. Analysis of the immune microenvironment showed higher immune infiltration and PD-L1 expression in patients responding to the inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Kimberley McGrail, Paula Granado-Martinez, Rosaura Esteve-Puig, Sara Garcia-Ortega, Yuxin Ding, Sara Sanchez-Redondo, Berta Ferrer, Javier Hernandez-Losa, Francesc Canals, Anna Manzano, Aura Navarro-Sabate, Ramon Bartrons, Oscar Yanes, Mileidys Perez-Alea, Eva Munoz-Couselo, Vicenc Garcia-Patos, Juan A. Recio
Summary: This study reveals that under metabolic stress, NRAS-mutant melanoma cells activate a glycolysis pathway dependent on BRAF, which enhances the efficacy of sorafenib when combined with glycolysis inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Iliana Lopez-Soldado, Adrian Gabriel Torres, Raul Ventura, Inma Martinez-Ruiz, Angels Diaz-Ramos, Evarist Planet, Diane J. Cooper, Agnieszka Pazderska, Krzysztof Wanic, Declan O'Hanlon, Donal J. O'Gorman, Teresa Carbonell, Lluis Ribas de Pouplana, John J. Nolan, Antonio Zorzano, Maria Isabel Hernandez-Alvareza
Summary: Type 2 diabetes mellitus (T2D) is a major contributor to morbidity and mortality, affecting millions of people worldwide. In this study, alterations in the expression of mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) in skeletal muscle of T2D patients were observed. The repression of mt-aaRSs expression was independent of age and could contribute to reduced protein synthesis in mitochondria. Additionally, an increased iNOS abundance in diabetic mice may inhibit the aminoacylation of mt-aaRSs, suggesting a regulatory role in diabetes.
Article
Developmental Biology
Rahma Said, Javier Hernandez-Losa, Amine Derouiche, Teresa Moline, Rosa Somoza Lopez de Haro, Skander Zouari, Ahlem Blel, Soumaya Rammeh, Slah Ouerhani
Summary: Despite the importance of epithelial-mesenchymal markers in prostate cancer, further research is needed to understand their role in diagnosis, cancer progression prevention, and treatment resistance prediction. A study with 111 PC patients and 16 healthy controls found underexpression of E-cadherin and ss-catenin in primary PC tissues, while Vimentin was overexpressed and associated with diagnosis, prognosis, and treatment resistance prediction. The study also identified a positive correlation between Vimentin and coronary heart disease in PC patients.
Article
Oncology
Fernando Lozano, Carles X. X. Raventos, Albert Carrion, Carme Dinares, Javier Hernandez, Enrique Trilla, Juan Morote
Summary: The urine biomarker XBM can predict early high-risk recurrences in non-muscle invasive bladder cancer (NMIBC), but it has low sensitivity and cannot replace cystoscopy and washing cytology.
Meeting Abstract
Medicine, Research & Experimental
Lourdes Salazar Huayna, Alexandra Navarro Jimenez, Jessica Camacho, Alfons Nadal, Joan Carles Ferreres, Javier Hernandez-Losa, Marta Sese, Teresa Moline, Lourdes Naranjo, Louis Moscoso, Santiago Ramon Y. Cajal, Marta Garrido-Pontnou
LABORATORY INVESTIGATION
(2022)