Article
Biochemistry & Molecular Biology
Yaozhong Hu, Yi Wang, Jing Lin, Sihao Wu, Huan Lv, Xuemeng Ji, Shuo Wang
Summary: This study developed several potential nanobodies that could serve as targeting moiety of drug conjugates. Among them, Nb60 showed promising characteristics and was considered as a potential candidate for tumor labeling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Jeeho Kim, Ho Jin You, Chakyung Youn
Summary: This study confirmed the abnormal decrease of SCARA3 in lung cancer, and overexpression of SCARA3 strongly inhibited tumor growth in lung cancer and induced apoptosis by increasing sensitivity of lung cancer cells to cisplatin.
Article
Cell Biology
Martina Tufano, Laura Marrone, Chiara D'Ambrosio, Valeria Di Giacomo, Simona Urzini, Yichuan Xiao, Monica Matuozzo, Andrea Scaloni, Maria Fiammetta Romano, Simona Romano
Summary: FKBP51 is crucial for the survival of cancer cells, especially melanoma. It involved in various signaling pathways and forms a complex with Akt and PHLPP, known for dephosphorylation of Akt. This study focuses on the regulation of Akt activation by canonical and spliced isoforms of FKBP51. The TPR domain of FKBP51 is found to mediate Akt ubiquitination at K63, an important step for Akt activation. Surprisingly, PHLPP does not promote Akt phosphorylation when silenced and even induces Akt phosphorylation when overexpressed. PHLPP stabilizes TRAF6, an E3 ubiquitin ligase, and supports K63-ubiquitination of Akt. The interactome profile of FKBP51 in melanoma cells emphasizes the crucial role of PHLPP in enhancing oncogenic characteristics, particularly cell proliferation.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Emanuela Guerra, Marco Trerotola, Valeria Relli, Rossano Lattanzio, Romina Tripaldi, Martina Ceci, Khouloud Boujnah, Ludovica Pantalone, Andrea Sacchetti, Kristina M. Havas, Pasquale Simeone, Nicole Travali, Patrizia Querzoli, Massimo Pedriali, Pietro Roversi, Manuela Iezzi, Nicola Tinari, Laura Antolini, Saverio Alberti
Summary: Trop-2 undergoes proteolytic activation by ADAM10 in cancer cells, exposing a previously inaccessible protein groove. A recognition strategy was designed to selectively target cancer cells. A cancer-specific antibody, 2G10, was generated and humanized into Hu2G10, which showed high affinity for cleaved/activated Trop-2 in cancer cells and moderate affinity for uncleaved/wtTrop-2 in normal cells. Hu2G10 effectively inhibited the growth of Trop-2-expressing breast, colon, and prostate cancers in vivo without causing systemic toxicity.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Cell Biology
Young Mi Kim, Sung-Hwa Ko, Yong-Il Shin, Yeonye Kim, Taehyung Kim, Jaehoon Jung, Sang-Yull Lee, Nam Gyun Kim, Kyoung-Jun Park, Ji Hyeon Ryu
Summary: The study demonstrated that blue LED irradiation suppressed pancreatic cancer cell and tumor growth by regulating the AKT/mTOR signaling pathway, while also increasing the expression of apoptosis-related proteins. These findings suggest that blue LEDs could be utilized as a nonpharmacological treatment for pancreatic cancer.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Plant Sciences
Yaling Hui, Ting Tang, Jing Wang, Huanhuan Zhao, Hong-Ying Yang, Junmin Xi, Baoxin Zhang, Jianguo Fang, Kun Gao, Yueting Wu
Summary: The study isolated a natural product FDC from an endophytic fungus of Lycium barbarum, which significantly inhibited proliferation in various human NSCLC cell lines through binding to intracellular iron to induce apoptosis.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Oncology
Chunxue Jiang, Xiaodi Zhao, Taejoo Jeong, Ju Young Kang, Jae Hyeon Park, In Su Kim, Hyung Sik Kim
Summary: Prostate cancer is a serious threat to male health globally, and chemotherapy resistance is a pressing issue. The discovery of novel molecules and chemotherapy strategies is crucial. This study identified a specific PKM2 inhibitor, compound 3h, and evaluated its anticancer effects through molecular and cellular experiments. The results demonstrated that compound 3h inhibits proliferation of LNCaP cells by inducing apoptosis, autophagy, and inhibiting glycolysis and mitochondrial respiration. This research provides a new approach for the development of novel chemotherapy for prostate cancer.
Article
Oncology
Jingping You, Qici Wu, Yunbing Li, Xiumin Li, Zhichao Lin, Jiafu Huang, Yu Xue, Alitongbieke Gulimiran, Yutian Pan
Summary: Lentinan (LNT) extracted from Lentinus edodes can inhibit the proliferation and promote apoptosis of mouse hepatocellular carcinoma (HCC) cells through the EGR1/PTEN/AKT axis.
Article
Biochemistry & Molecular Biology
Ghmkin Hassan, Said M. Afify, Juan Du, Hend M. Nawara, Mona Sheta, Sadia Monzur, Maram H. Zahra, Hagar A. Abu Quora, Hager Mansour, Samah El-Ghlban, Ryo Uesaki, Akimasa Seno, Masaharu Seno
Summary: The MEK inhibitor AZD-6244 plays a critical role in the conversion of iPS cells into CSCs, with the converted cells maintaining self-renewal ability, stemness gene expression, and increased migration and invasion abilities.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
EunJin Bang, Dae Hyun Kim, Hae Young Chung
Summary: This study shows that the PAR2 pathway plays a crucial role in skin photoaging, with inhibition of PAR2 effectively reducing inflammation and oxidative stress levels. PAR2 induces oxidative stress and inflammation through Akt-mediated phosphorylation of NF-kappa B and FoxO6, suggesting a key regulatory mechanism in ROS-mediated inflammatory response.
Article
Multidisciplinary Sciences
Xuelian Zhang, Ming Li, Wenjie Li, Linxiu Yue, Taiyuan Zhang, Qi Tang, Naidan Zhang, Xianyong Lan, Chuanying Pan
Summary: This study aims to investigate the damage of chlorpyrifos (CPF) on male reproduction in pigs and its potential molecular mechanisms. CPF was found to have broad-spectrum toxic effects on ST cells and porcine sperms. RNA sequencing and WB results suggest that CPF may regulate cell survival through the PI3K-AKT pathway. This study may lay the foundation for improving male fertility in pigs and provide theoretical information for human infertility.
Article
Oncology
Yabo Jiang, Yongzhen Tao, Xiuping Zhang, Xubiao Wei, Min Li, Xuxiao He, Bin Zhou, Weixing Guo, Huiyong Yin, Shuqun Cheng
Summary: The study identified that increased expression of miR-23a in HCC tissues is associated with worse survival, and miR-23a negatively regulates STAT5A to activate AKT signaling, leading to accelerated tumor growth. This indicates that the miR-23a-STAT5A-AKT signaling pathway plays a critical role in altering glucose metabolism in HCC and may provide new opportunities for effective therapy.
MOLECULAR ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ling Yin, Yongji Zeng, Renya Zeng, Yuanhong Chen, Tian-Li Wang, Kerry J. Rodabaugh, Fang Yu, Amarnath Natarajan, Adam R. Karpf, Jixin Dong
Summary: PKR plays a critical role in cancer treatment by regulating sensitivity to paclitaxel through controlling Bcl2 expression, presenting as a potential therapeutic target for recurrent drug-resistant ovarian tumors.
Article
Cell Biology
Shuyan Han, Zhihua Tian, Huifang Tian, Haibo Han, Jun Zhao, Yanna Jiao, Chunli Wang, Huifeng Hao, Shan Wang, Jialei Fu, Dong Xue, Hong Sun, Pingping Li
Summary: This study examined the role of hepatoma-derived growth factor (HDGF) in gefitinib resistance in non-small cell lung cancer (NSCLC) and identified the underlying mechanisms. The results showed that HDGF overexpression aggravated the malignant phenotype of NSCLC cells, while HDGF knockdown reversed these effects. The overexpression of HDGF also led to gefitinib resistance, while knockdown enhanced gefitinib sensitivity. Higher levels of HDGF in plasma or tumor tissue were associated with gefitinib resistance. HDGF activated the Akt and ERK signaling pathways, independent of EGFR phosphorylation, contributing to gefitinib resistance.
CELL DEATH DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Yanhong Wang, Xinyu Mang, Danni Li, Yiliang Chen, Zhenyu Cai, Fei Tan
Summary: In this study, the anti-neoplastic functions and mechanism of Piezo-CAP on hepatocellular carcinoma (HCC) were investigated. The results showed that Piezo-CAP could inhibit cell proliferation, migration and invasion, promote cell apoptosis and autophagy, and disrupt the survival pathways of redox deregulation, glycolysis, and PI3K/AKT/mTOR/HIF-1α signaling. Piezo-CAP has the potential to be a therapeutic approach for HCC.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Maria Chiara De Santis, Luca Gozzelino, Jean Piero Margaria, Andrea Costamagna, Edoardo Ratto, Federico Gulluni, Enza Di Gregorio, Erica Mina, Nicla Lorito, Marina Bacci, Rossano Lattanzio, Gianluca Sala, Paola Cappello, Francesco Novelli, Elisa Giovannetti, Caterina Vicentini, Silvia Andreani, Pietro Delfino, Vincenzo Corbo, Aldo Scarpa, Paolo Ettore Porporato, Andrea Morandi, Emilio Hirsch, Miriam Martini
Summary: This study reveals that loss of PI3K-C2 gamma in pancreatic ductal adenocarcinoma (PDAC) leads to hyperactivation of mTORC1 pathway and rewiring of glutamine metabolism, increasing tumor aggressiveness. Furthermore, PI3K-C2 gamma knockout tumors fail to adapt to metabolic stress induced by glutamine depletion, resulting in cell death. These findings suggest that targeting mTORC1 and glutamine metabolism may be a potential strategy for personalized treatment in PDAC with PI3K-C2 gamma loss.
Article
Cardiac & Cardiovascular Systems
Paola G. Simeone, Rossella Liani, Giuseppina Bologna, Romina Tripaldi, Augusto Di Castelnuovo, Pasquale Simeone, Damiano D'Ardes, Sebastiano Miscia, Francesco Cipollone, Marco Marchisio, Agostino Consoli, Paola Lanuti, Francesca Santilli
Summary: This study aimed to compare the levels of circulating extracellular vesicles (EV) and specific EV subtypes derived from platelets, endothelial cells, and leucocytes in high cardiovascular risk patients with and without type 2 diabetes (T2DM), and to investigate the effects of anti-diabetic drugs on EV levels. The results showed that patients with T2DM had lower levels of total EV, platelet-derived EV, and endothelial-derived EV. However, after adjusting for variables, including HbA1c, the differences in EV subtypes were no longer significant. Linear regression analysis revealed that HbA1c was inversely related to total EV and specific EV subtypes. Moreover, patients on metformin treatment had lower levels of platelet-derived EV, even after adjustment for various factors.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2023)
Review
Biochemistry & Molecular Biology
Giulia Catitti, Domenico De Bellis, Simone Vespa, Pasquale Simeone, Barbara Canonico, Paola Lanuti
Summary: Extracellular Vesicles (EVs) are circulating particles that carry proteins, lipids, RNAs, and DNA fragments, playing important roles in intercellular communication. EVs can regulate host immune response and exhibit both pro- and anti-inflammatory functions. Physical exercise has anti-inflammatory effects on the host's immune response. This review highlights the role of circulating EVs in the anti-inflammatory events associated with the regulation of the host's immune response during physical exercise.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Francesco Lorenzo Serafini, Andrea Delli Pizzi, Pasquale Simeone, Alberto Giammarino, Cristian Mannetta, Michela Villani, Jacopo Izzi, Davide Buca, Giulia Catitti, Piero Chiacchiaretta, Stefano Trebeschi, Sebastiano Miscia, Massimo Caulo, Paola Lanuti
Summary: Abdominal aortic aneurysm (AAA) is a common aortic disease that can be treated with open surgical repair (OSR) or endovascular aortic repair (EVAR). Follow-up monitoring using computed tomography angiography (CTA) for 5 years is necessary to prevent complications. However, CTA involves high radiation exposure. This study explores the potential of peripheral-blood-circulating extracellular vesicles (pbcEVs) as biomarkers for EVAR complications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nutrition & Dietetics
Konstantinos Efthymakis, Giuseppina Bologna, Pasquale Simeone, Laura Pierdomenico, Giulia Catitti, Simone Vespa, Angelo Milano, Domenico De Bellis, Francesco Laterza, Assunta Pandolfi, Caterina Pipino, Michele Sallese, Marco Marchisio, Sebastiano Miscia, Matteo Neri, Paola Lanuti
Summary: Extracellular vesicles (EVs) play important roles in intercellular communication, homeostasis maintenance, and diseases. This study aimed to assess and characterize circulating EVs in celiac disease patients and patients on a gluten-free diet (GFD) using a novel flow cytometry technique. The results showed significantly increased total EV counts in both newly diagnosed celiac disease patients and patients on GFD, while endothelial-derived and epithelial-derived EV counts were significantly decreased in subjects on gluten exclusion. These findings indicate that EVs could serve as potential disease-specific biomarkers in celiac disease.
Article
Oncology
Emanuela Guerra, Marco Trerotola, Valeria Relli, Rossano Lattanzio, Romina Tripaldi, Martina Ceci, Khouloud Boujnah, Ludovica Pantalone, Andrea Sacchetti, Kristina M. Havas, Pasquale Simeone, Nicole Travali, Patrizia Querzoli, Massimo Pedriali, Pietro Roversi, Manuela Iezzi, Nicola Tinari, Laura Antolini, Saverio Alberti
Summary: Trop-2 undergoes proteolytic activation by ADAM10 in cancer cells, exposing a previously inaccessible protein groove. A recognition strategy was designed to selectively target cancer cells. A cancer-specific antibody, 2G10, was generated and humanized into Hu2G10, which showed high affinity for cleaved/activated Trop-2 in cancer cells and moderate affinity for uncleaved/wtTrop-2 in normal cells. Hu2G10 effectively inhibited the growth of Trop-2-expressing breast, colon, and prostate cancers in vivo without causing systemic toxicity.
MOLECULAR CANCER THERAPEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Valentina Giansante, Gianmarco Stati, Silvia Sancilio, Emanuela Guerra, Saverio Alberti, Roberta Di Pietro, Joerg D. Hoheisel
Summary: Pancreatic cancer is the seventh leading cause of cancer-related death, and its incidence is increasing each year. The low relative survival rate and challenges of heterogeneity and tumor microenvironment in pancreatic cancer have emphasized the need for novel therapeutic strategies. This review focuses on the role of necroptosis in pancreatic cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Emanuela Guerra, Marco Trerotola, Saverio Alberti
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Dentistry, Oral Surgery & Medicine
Ilaria Cela, Vito Carlo Alberto Caponio, Emily Capone, Morena Pinti, Marco Mascitti, Lucrezia Togni, Lorenzo Lo Muzio, Corrado Rubini, Vincenzo De Laurenzi, Rossano Lattanzio, Vittoria Perrotti, Gianluca Sala
Summary: The present study suggests that LGALS3BP is highly expressed in oral squamous cell carcinoma (OSCC) and may serve as a potential diagnostic biomarker and therapeutic target for ADC-based therapy. The study also found a correlation between high LGALS3BP expression levels and aggressive histological features of OSCC. Additionally, OSCC cell lines with high LGALS3BP expression showed high sensitivity to the ADC-payload DM4.
Article
Oncology
Emanuela Guerra, Marco Trerotola, Valeria Relli, Rossano Lattanzio, Martina Ceci, Khouloud Boujnah, Ludovica Pantalone, Roberta Di Pietro, Manuela Iezzi, Nicola Tinari, Saverio Alberti
Summary: We developed the 2EF mAb to recognize Trop-2 in difficult-to-reach, densely packed tumor sites. The 2EF antibody efficiently accessed Trop-2 at cell-cell junctions in breast cancer cells and inaccessible sites in prostate tumors. It showed high anticancer activity on densely packed, Trop-2-expressing tumors and enhanced the activity of the 2G10 mAb against tumors in vivo.
Article
Genetics & Heredity
Marco Trerotola, Laura Antolini, Laura Beni, Emanuela Guerra, Mariano Spadaccini, Damiano Verzulli, Antonino Moschella, Saverio Alberti
Summary: The determinants of transcription factor amino acid-DNA base binding selectivity were identified, and a DNA recognition mode was discovered. This advances our understanding of gene expression regulation and has the potential for integration with higher-order complexity approaches.
NAR GENOMICS AND BIOINFORMATICS
(2022)