Article
Oncology
Angela Leo, Erica Pranzini, Laura Pietrovito, Elisa Pardella, Matteo Parri, Paolo Cirri, Gennaro Bruno, Maura Calvani, Silvia Peppicelli, Eugenio Torre, Maiko Sasaki, Lily Yang, Lei Zhu, Paola Chiarugi, Giovanni Raugei, Jack L. Arbiser, Maria Letizia Taddei
Summary: Metastatic melanoma is a highly aggressive and lethal cancer, with poor prognosis. The study investigated the potential of Claisened Hexafluoro, a chemical compound, in inhibiting amoeboid motility in melanoma cells. Results showed that by targeting mitochondrial activity, Claisened Hexafluoro could impede the dissemination process and decrease metastasis in vivo. This suggests a promising future therapeutic application for metastatic melanoma treatment.
Article
Multidisciplinary Sciences
Yingjie Liu, Peiyuan Zhang, Qiuyao Wu, Houqin Fang, Yuan Wang, Yansen Xiao, Min Cong, Tingting Wang, Yunfei He, Chengxin Ma, Pu Tian, Yajun Liang, Lun-Xiu Qin, Qingcheng Yang, Qifeng Yang, Lujian Liao, Guohong Hu
Summary: This study reveals the regulatory role of lncRNA NR2F1-AS1 in metastatic dormancy, promoting tumor dissemination but inhibiting proliferation in mesenchymal-like breast cancer stem-like cells. This connection between BCSC plasticity and metastatic dormancy highlights the importance of lncRNA in these processes.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Qianqian Gan, Kai Cui, Qi Cao, Ning Zhang, Min-Fu Yang, Xing Yang
Summary: The potential use of EphA2 as a target for detecting PSMA-negative prostate cancer has been demonstrated, and a radiolabeled ligand [F-18]AlF-ETN with high contrast has been developed for specifically imaging EphA2 expressing prostate cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Ashwin Sachdeva, Claire A. Hart, Kyungmin Kim, Thomas Tawadros, Pedro Oliveira, Jonathan Shanks, Mick Brown, Noel Clarke
Summary: This study investigated the influence of EphA2 signaling in prostate cancer (PCa) progression and long-term survival. The results showed that non-canonical EphA2 signaling, mediated by pEphA2(S897), plays a key role in transendothelial migration of PCa to bone marrow endothelium. High expression of EphA2 or pEphA2(S897) in a PTENlow background is associated with poor overall survival.
BRITISH JOURNAL OF CANCER
(2022)
Article
Multidisciplinary Sciences
Sara Garcia-Garcia, Maria Rodrigo-Faus, Noelia Fonseca, Sara Manzano, Balazs Gyorffy, Alberto Ocana, Paloma Bragado, Almudena Porras, Alvaro Gutierrez-Uzquiza
Summary: The study identifies MAP4K4 as a key gene in prostate cancer metastasis, with its deletion or inhibition blocking cell migration and clonogenic properties, suggesting a potential role of MAP4K4 in promoting tumor dissemination and growth. Moreover, the upregulation of HGK correlates with poor prognosis in prostate cancer, indicating its potential use as a prognostic biomarker for predicting aggressive phenotype and metastasis appearance.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Jan Pencik, Cecile Philippe, Michaela Schlederer, Emine Atas, Matteo Pecoraro, Sandra Grund-Groeschke, Wen (Jess) Li, Amanda Tracz, Isabel Heidegger, Sabine Lagger, Karolina Trachtova, Monika Oberhuber, Ellen Heitzer, Osman Aksoy, Heidi A. Neubauer, Bettina Wingelhofer, Anna Orlova, Nadine Witzeneder, Thomas Dillinger, Elisa Redl, Georg Greiner, David D'Andrea, Johnny R. Ostman, Simone Tangermann, Ivana Hermanova, Georg Schaefer, Felix Sternberg, Elena E. Pohl, Christina Sternberg, Adam Varady, Jaqueline Horvath, Dagmar Stoiber, Tim I. Malcolm, Suzanne D. Turner, Eileen E. Parkes, Brigitte Hantusch, Gerda Egger, Stefan Rose-John, Valeria Poli, Suneil Jain, Chris W. D. Armstrong, Gregor Hoermann, Vincent Goffin, Fritz Aberger, Richard Moriggl, Arkaitz Carracedo, Cathal McKinney, Richard D. Kennedy, Helmut Klocker, Michael R. Speicher, Dean G. Tang, Ali A. Moazzami, David M. Heery, Marcus Hacker, Lukas Kenner
Summary: PTEN and STAT3 are frequently co-deleted genes in metastatic prostate cancer (mPCa). STAT3 controls mPCa through the LKB1/pAMPK/mTORC1/CREB signaling pathway, and metformin can inhibit mPCa growth.
Article
Cell Biology
Clayton W. Molter, Eliana F. Muszynski, Yuanyuan Tao, Tanisha Trivedi, Anna Clouvel, Allen J. Ehrlicher
Summary: The study found that the contractility, cell stiffness, and motility of prostate cancer cells exhibit unique biophysical responses under different metastatic potential, which are influenced by substrate stiffness. Despite the biophysical diversity, the mechanical microenvironment is a key determinant in the biophysical response of PCa with variable metastatic potentials.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aide Negri, Marina Marozzi, Daniela Trisciuoglio, Dante Rotili, Antonello Mai, Federica Rizzi
Summary: Androgen deprivation therapy (ADT) is a common treatment for recurrent prostate cancer (PC), but ADT resistance often occurs leading to lethal metastatic castration-resistant prostate cancer (mCRPC). In this study, the combination of an EZH2 inhibitor with a BET inhibitor showed superior effects in inhibiting cell viability, proliferation, and clonogenic ability, and also reduced the expression of c-myc and NF-kB. These promising results suggest that this combination may be a suitable treatment option for mCRPC by targeting different molecular pathways.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Xuewei Zhang, Wataru Sakamoto, Daniel Canals, Masumi Ishibashi, Masaya Matsuda, Kentaro Nishida, Masafumi Toyoshima, Shogo Shigeta, Makoto Taniguchi, Can E. Senkal, Toshiro Okazaki, Nobuo Yaegashi, Yusuf A. Hannun, Takeshi Nabe, Kazuyuki Kitatani
Summary: Regulation of sphingolipid metabolism has a significant impact on cellular homeostasis and cancer progression. Dysregulation of ceramide-centered metabolism is associated with metastatic potential in ovarian cancer cells. Specifically, the CerS2-C-24:1-ceramide axis, possibly counteracted by neutral ceramidase, plays a key role in limiting cell motility and metastatic potential.
Article
Microbiology
Xiaoxiang Liu, Yifan Ye, Yin Zhu, Lifang Wang, Leyang Yuan, Junli Zhu, Aihua Sun
Summary: The study found that the mutant strain of Pseudomonas fluorescens with RpoN deletion had deficiencies in swimming motility, biofilm formation, and resistance, but increased resistance to H2O2. The mutant also significantly reduced the production of extracellular protease and total volatile basic nitrogen (TVB-N) in sterilized fish juice, while showing higher sensory scores. RNA-seq analysis revealed the important role of RpoN in regulating multiple cellular processes.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Oncology
Shu Lei, Xiangjun He, Xiao Yang, Xuan Gu, Yijiao He, Jianliu Wang
Summary: In this study, the correlation between DUSP1 and AP-1 complex in endometrial carcinoma was discovered. It was found that AP-1 complex might be the upstream transcriptional regulators of DUSP1. DUSP1 can inhibit tumor growth and invasion, and promote apoptosis by regulating ERK pathway or dephosphorylating EPHA2. EPHA2 is highly expressed in aggressive endometrial cancer patients, and the use of EPHA2 inhibitor can significantly slow down tumor cell growth.
Article
Oncology
Elena D. Czyrnik, Marc Wiesehoefer, Jaroslaw T. Dankert, Sven Wach, Mathias Wagner, Martin Spahn, Marianna Kruithof de Julio, Gunther Wennemuth
Summary: This study reveals the mechanism of cell-cell interaction via soluble factors in prostate carcinoma and highlights the importance of GALNT14.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Charlotte Cresens, Guillermo Solis-Fernandez, Astha Tiwari, Rik Nuyts, Johan Hofkens, Rodrigo Barderas, Susana Rocha
Summary: Clathrin assembles in various clathrin-coated structures (CCSs) at the plasma membrane of cells, including flat clathrin lattices (FCLs) found in specific cell types, including cancer cells. Our study revealed that FCLs are present in different colorectal cancer (CRC) cell lines and are highly stable, with lifetimes exceeding 8 hours. By combining advanced fluorescence imaging and analysis with cell models representing CRC metastasis, we discovered that CRC metastatic potential is associated with abnormal membranous clathrin distribution, resulting in a higher prevalence of FCLs in cells with greater metastatic potential. These findings suggest a potential unexplored role of clathrin organization in cancer metastasis.
Article
Oncology
Khalil H. Alshanqiti, Sumayyah F. Alomar, Nourah Alzoman, Aliyah Almomen
Summary: This study investigated the potential impact of irisin on prostate cancer cells and its underlying mechanism. Results showed that irisin inhibited tumor growth and progression by altering alpha V beta 5 and the Bcl2/BAX and P13k-Akt signaling pathway in vivo. These findings provide a foundation for further evaluation of irisin's role in prostate cancer.
Article
Biochemistry & Molecular Biology
Cho-Won Kim, Hong Kyu Lee, Min-Woo Nam, Youngdong Cho, Kyung-Chul Choi
Summary: KiSS1 promotes the proliferation, migration, and metastasis of liver cancer cells, which is associated with changes in the expressions of epithelial mesenchymal transition-related genes and increased angiogenic capacity.
MOLECULES AND CELLS
(2022)
Article
Oncology
Luigi Ippolito, Giuseppina Comito, Matteo Parri, Marta Iozzo, Assia Duatti, Francesca Virgilio, Nicla Lorito, Marina Bacci, Elisa Pardella, Giada Sandrini, Francesca Bianchini, Roberta Damiano, Lavinia Ferrone, Giancarlo la Marca, Sergio Serni, Pietro Spatafora, Carlo V. Catapano, Andrea Morandi, Elisa Giannoni, Paola Chiarugi
Summary: This research reveals that lactate can promote lipid metabolism in prostate cancer cells through the regulation of gene expression, thus contributing to cancer progression and metastasis.
Article
Chemistry, Medicinal
Theodora Chatzisideri, George Leonidis, Theodoros Karampelas, Eleni Skavatsou, Angeliki Velentza-Almpani, Francesca Bianchini, Constantin Tamvakopoulos, Vasiliki Sarli
Summary: In this study, c(RGDyK)-based conjugates of gemcitabine (GEM) with the carbonate and carbamate linkages in the 6-OH group of GEM were synthesized for targeted delivery to integrin alpha(v)beta(3) overexpressing cancer cells. Among the synthesized conjugates, TC113 bearing the carbamate linker showed stability in human plasma and potent antiproliferative properties against WM266.4 and A549 cells, making it a promising candidate for further clinical applications.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Lorenzo Baldini, Elena Lenci, Francesca Bianchini, Andrea Trabocchi
Summary: Molecular targets in tumor angiogenesis include VEGF, integrin receptors, and MMPs. Inhibiting these targets can help block tumor cell invasion and metastasis. Combining the inhibition of alpha(v)beta(3) and MMP2 as a multitarget approach can deliver a synergistic blockade of tumor cell migration, invasion, and metastasis.
Review
Oncology
Erica Pranzini, Giovanni Raugei, Maria Letizia Taddei
Summary: Tumor recurrence is a major challenge for cancer patients, as cancer cells can enter a dormant state before re-emerging. The mechanisms behind this dormant state and subsequent awakening are largely unknown, but cancer metabolism is gaining attention as a critical driver of tumor progression. This review focuses on the metabolic adaptations of dormant cancer cells and their role in tumor re-growth. Understanding these metabolic pathways could lead to novel therapeutic approaches to prevent tumor recurrence.
Article
Biochemistry & Molecular Biology
Lorenzo Calugi, Elena Lenci, Francesca Bianchini, Alessandro Contini, Andrea Trabocchi
Summary: Asparagine endopeptidase, also known as legumain, is a pH-dependent cysteine protease that cleaves substrates after asparagine residues. Recent studies have found its involvement in neurological diseases like Alzheimer's disease. Researchers synthesized compounds with different substituents and discovered one with nanomolar-range inhibition potency.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Kelly Bugatti, Elena Andreucci, Noemi Monaco, Lucia Battistini, Silvia Peppicelli, Jessica Ruzzolini, Claudio Curti, Franca Zanardi, Francesca Bianchini, Andrea Sartori
Summary: This study reports the synthesis and in vitro biological evaluation of three new covalent conjugates, consisting of an alpha(V)beta(6) integrin-recognizing small cyclopeptide and nintedanib, for the treatment of fibrotic diseases. One of these conjugates demonstrates optimal antifibrotic properties in vitro. The integrin ligand within the conjugate plays a role in inhibiting fibrotic stimuli and enhancing the effect of nintedanib, while selectively targeting cells overexpressing alpha(V)beta(6) integrin.
Article
Biochemistry & Molecular Biology
Simona Delle Monache, Fanny Pulcini, Francesca Santilli, Stefano Martellucci, Costantino Santacroce, Jessica Fabrizi, Adriano Angelucci, Maurizio Sorice, Vincenzo Mattei
Summary: Studies suggest that hypoxia treatment of DPSCs promotes their differentiation into neuronal cells in a time-dependent manner. Additionally, the conditioned media from hypoxia-stimulated DPSCs can induce neural differentiation in other neural cells.
Review
Oncology
Barbara Di Francesco, Daniela Verzella, Daria Capece, Davide Vecchiotti, Mauro Di Vito Nolfi, Irene Flati, Jessica Cornice, Monica Di Padova, Adriano Angelucci, Edoardo Alesse, Francesca Zazzeroni
Summary: Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with a high need for new therapeutic options. Constitutive NF-kappa B activation has been reported in around 40% of AML patients, making targeting the NF-kappa B pathway an attractive strategy to treat AML.
Article
Biochemistry & Molecular Biology
Riccardo Innocenti, Caterina Dallari, Elena Lenci, Francesco S. Pavone, Francesca Bianchini, Caterina Credi, Andrea Trabocchi
Summary: This paper reports the synthesis of a novel functionalized triazole-based RGD peptidomimetic and its covalent conjugation on pegylated gold nanostars. These highly stable nanoconstructs showed a multivalent effect in binding alpha vS3 integrin receptors and proved to inhibit M21 cell adhesion at 25 pM concentration. Targeted gold nanostars with peculiar surface plasmon resonance in the NIR transparent window may represent a promising agent for anticancer multi-modality treatments.
BIOORGANIC CHEMISTRY
(2022)
Review
Oncology
Elena Andreucci, Silvia Peppicelli, Jessica Ruzzolini, Francesca Bianchini, Lido Calorini
Summary: Tumour vascularisation is crucial for cancer sustainment, with vasculogenic mimicry (VM) gaining increasing interest as a potential target for cancer treatment. Unlike healthy tissue vessels, tumour vasculature is heterogeneous and tortuous, hindering efficient chemotherapy delivery and facilitating cancer cell metastasis. The disorganisation of tumour vessels contributes to a self-reinforcing vicious circle, promoting cancer malignancy and progression. Hypoxia and acidosis within tumours, which are hallmark features of cancer, induce vascularisation and create a permissive microenvironment for cancer progression and dissemination. Targeting hypoxia and acidosis may represent a potential strategy to treat VM and impede tumour perfusion and cancer cell sustainment.
CANCER AND METASTASIS REVIEWS
(2022)
Article
Chemistry, Organic
Kelly Bugatti, Andrea Sartori, Lucia Battistini, Jessica Ruzzolini, Chiara Nediani, Claudio Curti, Francesca Bianchini, Franca Zanardi
Summary: Melanoma, the deadliest form of skin cancer, is increasing in incidence. New studies have shown the potential of combining nintedanib with immuno- and/or targeted therapy drugs in melanoma treatment.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Oncology
Elena Andreucci, Jessica Ruzzolini, Francesca Bianchini, Giampaolo Versienti, Alessio Biagioni, Matteo Lulli, Daniele Guasti, Patrizia Nardini, Simona Serrati, Francesca Margheri, Anna Laurenzana, Chiara Nediani, Silvia Peppicelli, Lido Calorini
Summary: Cutaneous melanoma is a highly metastatic form of skin cancer, and current treatments have limited effectiveness. This study focuses on the role of extracellular vesicles (EV) in melanoma metastasis. The researchers found that melanoma cells release more EV enriched with miR-214 in an acidic environment, which activates macrophages and promotes the trans-endothelial migration of melanoma cells. This discovery suggests that targeting miR-214 could be a potential therapeutic strategy for preventing melanoma intravasation.
Article
Biochemistry & Molecular Biology
Elena Andreucci, Kelly Bugatti, Silvia Peppicelli, Jessica Ruzzolini, Matteo Lulli, Lido Calorini, Lucia Battistini, Franca Zanardi, Andrea Sartori, Francesca Bianchini
Summary: Growth factors and cytokines in the lung cancer microenvironment induce EMT and promote tumor progression. A novel conjugate targeting the α v β 6 integrin receptor, linked to the kinase inhibitor nintedanib, inhibits cancer cell adhesion and growth through selective delivery. The conjugate also suppresses clonogenic ability and other aspects associated with EMT transition, offering a precise strategy against non-small cell lung cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Samantha Sabetta, Davide Vecchiotti, Letizia Clementi, Mauro Di Vito Nolfi, Francesca Zazzeroni, Adriano Angelucci
Summary: Three-dimensional cell culture methods, particularly the 3D multicellular tumor spheroids model, enhance the predictive relevance of in vitro tumor models by better resembling tumor complexity and drug resistance. Recent advancements in 3D printing techniques and suitable biomaterials have provided new opportunities for developing reproducible and high-throughput 3D tissue cultures. In this study, the comparison of DU145 and U87 cancer cells cultured in the 3D spheroids model and the 3D bioprinting model showed that bioprinted cells demonstrated similar drug resistance to spheroids, suggesting a potential mechanism of drug resistance. The 3D bioprinted model utilizing alginate/gelatin hydrogel was proven to be a feasible, reproducible, and scalable model for drug screening when spheroid growth is required.
Article
Biochemistry & Molecular Biology
Chiara Compagnoni, Roberta Capelli, Veronica Zelli, Alessandra Corrente, Davide Vecchiotti, Irene Flati, Mauro Di Vito Nolfi, Adriano Angelucci, Edoardo Alesse, Francesca Zazzeroni, Alessandra Tessitore
Summary: This study aimed to explore the expression levels and functional relationships between miR-182-5p and Cyld-Foxo1 in hepatic tissues from a diet-induced NAFLD/HCC mouse model. The results showed that miR-182-5p was upregulated during NAFLD progression and in tumors, and it inhibited the expression of tumor-suppressor genes Cyld and Foxo1 in HepG2 cells. Analysis of human HCC samples confirmed these findings and demonstrated the potential of miR-182-5p as a diagnostic biomarker or therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)