Review
Oncology
Qingfan Zheng, Bin Zhang, Changfeng Li, Xuewen Zhang
Summary: Cholangiocarcinoma (CCA) is a poor prognostic tumor with limited treatment options. Inability to replicate patient tumor characteristics in preclinical models hinders development of effective therapies. Improving patient outcomes can be achieved through developing combination therapies and better preclinical experimental models.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Annamaria Massa, Caterina Peraldo-Neia, Francesca Vita, Chiara Varamo, Marco Basirico, Chiara Raggi, Paola Bernabei, Jessica Erriquez, Ivana Sarotto, Francesco Leone, Serena Marchio, Giuliana Cavalloni, Massimo Aglietta
Summary: The study demonstrates that paclitaxel has anti-tumor activity in multidrug-resistant intrahepatic cholangiocarcinoma by affecting the cell cycle and inducing apoptosis, impairing the stem cell compartment. A therapeutic regimen containing albumin-bound nanoparticle paclitaxel overcomes drug resistance and delays tumor growth, reducing glucose uptake.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chao-Jen Wong, Jennifer L. Whiddon, Ashlee T. Langford, Andrea E. Belleville, Stephen J. Tapscott
Summary: Mis-expression of DUX4 in skeletal muscle causes facioscapulohumeral muscular dystrophy (FSHD). Dogs have a DUXC gene that is similar to DUX4 and Dux, and the expression of DUXC in canine cells induces a pluripotent program similar to DUX4 and Dux. The conservation of homeodomains and transcriptional program activation between human DUX4 and canine DUXC suggests the potential use of DUXC-containing mammals for preclinical models of FSHD.
HUMAN MOLECULAR GENETICS
(2022)
Article
Oncology
Bing Zhu, Xinyan Wang, Takaya Shimura, Andrew C. Huang, Nana Kong, Yujie Dai, Jianmin Fang, Peng Guo, Jie-Er Ying
Summary: This preclinical study reports two effective targeted therapeutics for the treatment of cholangiocarcinoma. By conjugating ICAM1 antibodies with different cytotoxic payloads, tumor growth was successfully attenuated. This study paves the road for developing a promising targeted therapeutic candidate for clinical treatment of cholangiocarcinoma.
NPJ PRECISION ONCOLOGY
(2023)
Article
Cell Biology
Yuanyuan Shi, Xiaowen Cui, Tianyi Jiang, Yufei Pan, Yunkai Lin, Xiaofan Feng, Zhiwen Ding, Chun Yang, Yexiong Tan, Hongyang Wang, Liwei Dong
Summary: In this study, several compound candidates were identified through a high-throughput drug screen as potential treatments for CCA. The KSP inhibitors showed significant cytotoxic effects on CCA cells, leading to mitotic arrest and cell death. Clinical data and the TCGA database also revealed that KIF11 expression was abundant in CCA tumor specimens and correlated with poor outcomes in CCA patients.
CELL DEATH & DISEASE
(2022)
Article
Chemistry, Medicinal
Edward Price, J. Cory Kalvass, David DeGoey, Balakrishna Hosmane, Stella Doktor, Kelly Desino
Summary: This study evaluated different models for predicting human intestinal absorption data, providing a resource for DMPK scientists and medicinal/computational chemists to enhance their understanding of the utility and applications of permeability and absorption models for academia and industry.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Hugo Passos Vicari, Keli Lima, Leticia Veras Costa-Lotufo, Joao Agostinho Machado-Neto
Summary: This study demonstrates the potential efficacy of eribulin in hematologic cancers and identifies potential biomarkers of responsiveness. Eribulin shows selective effects on malignant blood cells and induces DNA damage and apoptosis markers. Combining eribulin with elacridar may overcome drug resistance in these diseases.
Article
Gastroenterology & Hepatology
Diego Calvisi, Luke Boulter, Javier Vaquero, Anna Saborowski, Luca M. Fabris, Pedro Rodrigues, Cedric E. Coulouarn, Rui Castro, Oreste Segatto, Chiara Raggi, Luc J. W. van der Laan, Guido Carpino, Benjamin Goeppert, Stephanie J. Roessler, Timothy Kendall, Matthias Evert, Ester W. Gonzalez-Sanchez, Juan Valle, Arndt Vogel, John J. Bridgewater, Mitesh J. Borad, Gregory R. Gores, Lewis Roberts, Jose J. G. B. Marin, Jesper Andersen, Domenico Alvaro, Alejandro M. Forner, Jesus Banales, Vincenzo Cardinale, Rocio I. R. Macias, Silve Vicent, Xin Chen, Chiara Braconi, Monique M. A. Verstegen, Laura Fouassier, Lewis Roberts, Alexander Scheiter, Florin M. Selaru, Katja Evert, Kirsten Utpatel, Laura Broutier, Massimiliano Cadamuro, Meritxell Huch, Robert Goldin, Sergio A. Gradilone, Yoshimasa Saito
Summary: In this Consensus Statement, experts provide recommendations on the criteria for preclinical models of cholangiocarcinoma (CCA) to increase disease understanding and develop novel therapeutic approaches.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Oncology
Brennan P. Bergeron, Jonathan D. Diedrich, Yang Zhang, Kelly R. Barnett, Qian Dong, Daniel C. Ferguson, Robert J. Autry, Wenjian Yang, Baranda S. Hansen, Colton Smith, Kristine R. Crews, Yiping Fan, Ching-Hon Pui, Shondra M. Pruett-Miller, Mary Relling, Jun J. Yang, Chunliang Li, William E. Evans, Daniel Savic
Summary: Glucocorticoids (GCs), as a common drug in the treatment of childhood acute lymphoblastic leukemia (ALL), face challenges of drug resistance. This study investigated the gene regulatory response to GCs in ALL cell lines and discovered disruptions in cis-regulatory elements that are associated with GC resistance. Integrating these findings with genetic and epigenetic datasets from primary ALL cells, the study also identified cis-regulatory disruptions that impact GC resistance in childhood ALL.
Article
Rheumatology
Chiara Bellocchi, Lorenzo Beretta, Xuan Wang, Marka A. Lyons, Maurizio Marchini, Maurizio Lorini, Vincenzo Carbonelli, Nicola Montano, Shervin Assassi
Summary: This study investigated the global gene expression profile of peripheral blood cells (PBCs) in the preclinical stage of systemic sclerosis (PreSSc), and found that there are molecular differences at the transcriptomic level already present in the preclinical stages of SSc. The reduced NK cell signature in PBCs is related to the progression of SSc over time.
Article
Multidisciplinary Sciences
Shengjie Fan, Yingxuan Yan, Ying Xia, Zhenyu Zhou, Lingling Luo, Mengnan Zhu, Yongli Han, Deqiang Yao, Lijun Zhang, Minglv Fang, Lina Peng, Jing Yu, Ying Liu, Xiaoyan Gao, Huida Guan, Hongli Li, Changhong Wang, Xiaojun Wu, Huanhu Zhu, Yu Cao, Cheng Huang
Summary: Using C. elegans as a model, researchers found that nomilin, a compound found in citrus fruit, significantly extended the lifespan, healthspan, and toxin resistance of the nematodes. This anti-aging effect was dependent on specific pathways and nuclear hormone receptors. Additionally, nomilin was identified to directly bind with the human pregnane X receptor (hPXR). In animal studies, dietary supplementation of nomilin improved healthspan and lifespan, and induced a gene signature associated with longevity.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Yang Gao, Rong Zhou, Jun-Feng Huang, Bo Hu, Jian-Wen Cheng, Xiao-Wu Huang, Peng-Xiang Wang, Hai-Xiang Peng, Wei Guo, Jian Zhou, Jia Fan, Xin-Rong Yang
Summary: In this study, patient-derived xenograft (PDX) models were successfully established for intrahepatic cholangiocarcinoma (ICC), demonstrating a close resemblance to parental tumors. Successful PDX engraftment was associated with certain clinicopathologic features and correlated with shorter time to recurrence and worse overall survival in patients. PDX models not only guided clinical treatment but also revealed potential biomarkers for drug resistance, such as CDH1 in lenvatinib resistance.
FRONTIERS IN ONCOLOGY
(2021)
Letter
Oncology
Sajid Khan, Janet Wiegand, Peiyi Zhang, Wanyi Hu, Dinesh Thummuri, Vivekananda Budamagunta, Nan Hua, Lingtao Jin, Carmen J. Allegra, Scott E. Kopetz, Maria Zajac-Kaye, Frederic J. Kaye, Guangrong Zheng, Daohong Zhou
Summary: KRAS(G12C) mutation is associated with tumor identification and its sensitivity to current treatments. This study demonstrates the synergistic effect of sotorasib and DT2216 combination therapy on certain KRAS(G12C) tumor cell lines, leading to enhanced efficacy in treating these tumors.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Daniel R. Principe, Alexandre F. Aissa, Sandeep Kumar, Thao N. D. Pham, Patrick W. Underwood, Rakesh Nair, Rong Ke, Basabi Rana, Jose G. Trevino, Hidayatullah G. Munshi, Elizaveta Benevolenskaya, Ajay Rana
Summary: There is currently no effective treatment for pancreatic ductal adenocarcinoma (PDAC). In this study, researchers identified a subset of gemcitabine-resistant tumor cells enriched for calcium/calmodulin signaling. Inhibition of calcium-dependent calmodulin activation led to the loss of drug-resistant phenotypes, and calcium chelation or depletion impaired ERK activation and restored therapeutic responses to gemcitabine. Calcium channel blockers also enhanced therapeutic responses to gemcitabine.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Gang Yang, Wenfang Guan, Zhe Cao, Wenbo Guo, Guangbing Xiong, Fangyu Zhao, Mengyu Feng, Jiangdong Qiu, Yueze Liu, Michael Q. Zhang, Lei You, Taiping Zhang, Yupei Zhao, Jin Gu
Summary: This study identified key genes and microRNA associated with gemcitabine resistance in pancreatic cancer cells, and potential biomarker miR-135a-5p for predicting drug response. Moreover, changes in PI3K-Akt, p53, and hypoxia-inducible factor-1 pathways were observed in multiple patients before and after treatment, suggesting potential target pathways for reducing acquired resistance.
CLINICAL CANCER RESEARCH
(2021)
Article
Dermatology
M. Scatolini, A. Patel, E. Grosso, M. Mello-Grand, P. Ostano, R. Coppo, M. Vitiello, T. Venesio, A. Zaccagna, A. Pisacane, I Sarotto, D. Taverna, L. Poliseno, D. Bergamaschi, G. Chiorino
Summary: The study identified a significant association between metastases, BRAF mutation, and low GJB5 expression in melanoma, suggesting a potential prognostic role for GJB5 in cutaneous melanoma.
BRITISH JOURNAL OF DERMATOLOGY
(2022)
Article
Oncology
Annamaria Massa, Caterina Peraldo-Neia, Francesca Vita, Chiara Varamo, Marco Basirico, Chiara Raggi, Paola Bernabei, Jessica Erriquez, Ivana Sarotto, Francesco Leone, Serena Marchio, Giuliana Cavalloni, Massimo Aglietta
Summary: The study demonstrates that paclitaxel has anti-tumor activity in multidrug-resistant intrahepatic cholangiocarcinoma by affecting the cell cycle and inducing apoptosis, impairing the stem cell compartment. A therapeutic regimen containing albumin-bound nanoparticle paclitaxel overcomes drug resistance and delays tumor growth, reducing glucose uptake.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Enrico Berrino, Laura Annaratone, Paolo Detillo, Dora Grassini, Alberto Bragoni, Anna Sapino, Benedetta Bussolati, Giovanni Bussolati, Caterina Marchio
Summary: Removing formic acid can significantly improve DNA preservation. ADF fixation reduces DNA fragmentation.
Article
Genetics & Heredity
Enrico Berrino, Laura Annaratone, Sara Erika Bellomo, Giulio Ferrero, Amedeo Gagliardi, Alberto Bragoni, Dora Grassini, Simonetta Guarrera, Caterina Parlato, Laura Casorzo, Mara Panero, Ivana Sarotto, Silvia Giordano, Matteo Cereda, Filippo Montemurro, Riccardo Ponzone, Nicola Crosetto, Alessio Naccarati, Anna Sapino, Caterina Marchio
Summary: HLBCs have distinct genomic features compared to HER2-positive and HER2-negative BCs, with differences across IHC classes. HLBC-2E category has the most distinctive features, while HLBC-1 is nearly identical to HER2-negative disease. Further studies are needed to determine whether the four genomic-driver classes of the LAURA classification have prognostic and/or predictive implications.
Article
Oncology
Alessandra Merlini, Maria Laura Centomo, Giulio Ferrero, Giulia Chiabotto, Umberto Miglio, Enrico Berrino, Giorgia Giordano, Silvia Brusco, Alberto Pisacane, Elena Maldi, Ivana Sarotto, Federica Capozzi, Cristina Lano, Claudio Isella, Giovanni Crisafulli, Massimo Aglietta, Angelo Paolo Dei Tos, Marta Sbaraglia, Dario Sangiolo, Lorenzo D'Ambrosio, Alberto Bardelli, Ymera Pignochino, Giovanni Grignani
Summary: The study identified an 8-gene expression signature to improve prediction of response to the trabectedin+olaparib combination in BSTS patients. The predictive role of these potential biomarkers warrants further investigation.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Vito Amodio, Simona Lamba, Rosaria Chila, Chiara M. Cattaneo, Benedetta Mussolin, Giorgio Corti, Giuseppe Rospo, Enrico Berrino, Claudio Tripodo, Federica Pisati, Alice Bartolini, Maria Costanza Aquilano, Silvia Marsoni, Gianluca Mauri, Caterina Marchio, Sergio Abrignani, Federica Di Nicolantonio, Giovanni Germano, Alberto Bardelli
Summary: Patients with DNA mismatch repair deficiency (MMRd) in colorectal cancer (CRC) often respond to immune checkpoint blockade therapies, while those with mismatch repair-proficient (MMRp) tumors generally do not. MMRp CRCs with variable fractions of MMRd cells may impact immune surveillance. Modulation of the MMRd fraction in MMR heterogeneous tumors can enhance their immunogenicity.
Article
Oncology
Filippo Pietrantonio, Paolo Manca, Sara Erika Bellomo, Simona Corso, Alessandra Raimondi, Enrico Berrino, Federica Morano, Cristina Migliore, Monica Niger, Lorenzo Castagnoli, Serenella Maria Pupa, Caterina Marchio, Maria Di Bartolomeo, Eleonora Restuccia, Chiara Lambertini, Josep Tabernero, Silvia Giordano
Summary: In the JACOB trial, the addition of pertuzumab to trastuzumab-chemotherapy did not significantly improve the survival of patients with metastatic HER2-positive gastric cancer. However, HER2 copy-number variation and AMNESIA panel may help in selecting patients who will benefit from HER2 inhibition. The analysis of HER2 CNV, HER2 expression, and AMNESIA showed correlations with overall response rate, progression-free survival, and overall survival.
CLINICAL CANCER RESEARCH
(2023)
Article
Pathology
Enrico Berrino, Maria Costanza Aquilano, Emanuele Valtorta, Vito Amodio, Giovanni Germano, Marco Gusmini, Katiuscia Gizzi, Elisabetta Fenocchio, Anna Sapino, Silvia Marsoni, Andrea Sartore-Bianchi, Alberto Bardelli, Salvatore Siena, Emanuela Bonoldi, Caterina Marchio
Summary: Colorectal cancer cells often exhibit homogeneous retention or loss of mismatch repair (MMR) protein expression, but rare cases show heterogeneous patterns. In this study, 200 colorectal cancers were analyzed for MMR protein expression, resulting in three groups: proficient MMR, deficient MMR, and heterogeneous MMR expression. Heterogeneous MMR tumors were further examined and compared to the other groups, revealing differential gene expression patterns and increased tumor-infiltrating lymphocytes.
Article
Pathology
Alberto Pisacane, Eliano Cascardi, Enrico Berrino, Alessio Polidori, Ivana Sarotto, Laura Casorzo, Mara Panero, Carla Boccaccio, Federica Verginelli, Silvia Benvenuti, Miriam Dellino, Paolo Comoglio, Filippo Montemurro, Elena Geuna, Caterina Marchio, Anna Sapino
Summary: The aim of this study is to develop a simplified pathological workflow to exclude CUPs in patients with MUOs. A total of 64 MUOs were classified using standard histopathology, and clinical data, immunocytochemical markers, and molecular analysis results were recorded. The majority of MUOs were confirmed as CUP, while a small portion displayed clear carcinoma features. The findings support the use of a simplified histological approach to exclude CUP and early metastatic cancers.
Article
Oncology
Erica Torchiaro, Consalvo Petti, Sabrina Arena, Francesco Sassi, Giorgia Migliardi, Alfredo Mellano, Roberta Porporato, Marco Basirico, Loretta Gammaitoni, Enrico Berrino, Monica Montone, Giorgio Corti, Giovanni Crisafulli, Caterina Marchio, Alberto Bardelli, Enzo Medico
Summary: High-grade mucinous colorectal cancer (HGM CRC) is an aggressive subtype that is difficult to treat, often accompanied by signet ring cancer cells. The development of patient-derived preclinical models for this subtype is crucial in oncology. In this study, successful propagation of preclinical models from a Lynch syndrome patient with refractory HGM CRC was achieved, providing a valuable tool for exploring alternative treatments. Inhibition of the proteasome by bortezomib and the NEDD8 pathway by pevonedistat showed promising results in both in vitro and in vivo testing, highlighting their potential as effective therapeutic approaches against Lynch syndrome-associated HGM CRC.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Annalisa Petrelli, Sabrina Rizzolio, Filippo Pietrantonio, Sara E. Bellomo, Matteo Benelli, Loris De Cecco, Dario Romagnoli, Enrico Berrino, Claudia Orru, Salvatore Ribisi, Daniel Moya-Rull, Cristina Migliore, Daniela Conticelli, Irene M. Maina, Elisabetta Puliga, Violeta Serra, Benedetta Pellegrino, Alba Llop-Guevara, Antonino Musolino, Salvatore Siena, Andrea Sartore-Bianchi, Michele Prisciandaro, Federica Morano, Maria Antista, Uberto Fumagalli, Giovanni De Manzoni, Maurizio Degiuli, Gian Luca Baiocchi, Marco F. Amisano, Alessandro Ferrero, Caterina Marchio, Simona Corso, Silvia Giordano
Summary: Although clinical trials on gastric cancer patients have shown negative results, PARP inhibitors (PARPis) still have potential as a therapy for a subpopulation of gastric cancer patients. An estimated 7% to 12% of gastric cancers have mutations associated with HR failure, suggesting possible benefits from PARPis. Preclinical trials using patient-derived xenografts (PDXs) and primary cells showed that olaparib was effective in PDXs with BRCA2 mutations. Additionally, evaluation of HR deficiency and mutational signatures effectively stratified responders and nonresponders.
Article
Multidisciplinary Sciences
Giovanna Chiorino, Elisabetta Petracci, Emir Sehovic, Ilaria Gregnanin, Elisa Camussi, Maurizia Mello-Grand, Paola Ostano, Emilia Riggi, Viviana Vergini, Alessia Russo, Enrico Berrino, Andrea Ortale, Francesca Garena, Tiziana Venesio, Federica Gallo, Elisabetta Favettini, Alfonso Frigerio, Giuseppe Matullo, Nereo Segnan, Livia Giordano
Summary: The objective of this study was to identify circulating microRNA (miRs) ratios associated with breast cancer (BC) in women attending mammography screening. By using small-RNA sequencing and RT-qPCR techniques, the study identified 7 miR ratios associated with BC, as well as non-molecular factors such as body mass index, menopausal status, lifestyle, and breast density. The resulting model achieved an ROC AUC of 0.79, with a sensitivity and specificity of 71.9% and 76.6%, respectively. This is the first study report circulating miRs for BC detection in a screening setting.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Alessio Rizzo, Ornella Cantale, Andrea Mogavero, Lucia Garetto, Manuela Racca, Tiziana Venesio, Shobana Anpalakhan, Silvia Novello, Vanesa Gregorc, Giuseppe Luigi Banna
Summary: This study investigated the correlation between [F-18] FDG-PET/CT SUVratio and peripheral blood inflammatory indexes in NSCLC patients, and explored their role in predicting overall survival and progression-free survival. The results showed no significant correlation between [F-18] FDG-PET/CT uptake in different anatomical sites and tumor and systemic immune-inflammatory indexes.