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Rodrigo Romero, Tinyi Chu, Tania J González-Robles, Perianne Smith, Yubin Xie, Harmanpreet Kaur, Sara Yoder, Huiyong Zhao, Chenyi Mao, Wenfei Kang, Maria V Pulina, Kayla E Lawrence, Anuradha Gopalan, Samir Zaidi, Kwangmin Yoo, Jungmin Choi, Ning Fan, Olivia Gerstner, Wouter R Karthaus, Elisa DeStanchina, Kelly V Ruggles, Peter M K Westcott, Ronan Chaligné, Dana Pe'er, Charles L Sawyers
Lineage plasticity is a recognized hallmark of cancer progression that can shape therapy outcomes. The underlying cellular and molecular mechanisms mediating lineage plasticity remain poorly understood. Here, we describe a versatile in vivo platform to identify and interrogate the molecular determinants of neuroendocrine lineage transformation at different stages of prostate cancer progression. Adenocarcinomas reliably develop following orthotopic transplantation of primary mouse prostate organoids acutely engineered with human-relevant driver alterations (e...
April 11, 2024: bioRxiv
#22
Ruihan Luo, Jiajia Liu, Jianguo Wen, Xiaobo Zhou
Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells...
April 5, 2024: Research Square
#23
Piotr Dzien, Ximena Raffo Iraolagoitia, Stephanie May, David Stevenson, Lynn McGarry, Dmitry Soloviev, Gavin Brown, Colin Nixon, Chrysa Kapeni, Maike De La Roche, Karen Blyth, Scott Lyons, Thomas Bird, Douglas Strathdee, Gilbert Fruhwirth, Leo Carlin, David Lewis
Imaging reporter genes are indispensable for visualising biological processes in living subjects, particularly in cancer research where they have been used to observe tumour development, cancer cell dissemination, and treatment response. Engineering reporter genes into the germline frequently involves single imaging modality reporters operating over limited spatial scales. To address these limitations, we developed an inducible triple-reporter mouse model (Rosa26 LSL - NRL ) that integrates reporters for complementary imaging modalities, fluorescence, bioluminescence and positron emission tomography (PET), along with inducible Cre-lox functionality for precise spatiotemporal control of reporter expression...
April 3, 2024: Research Square
#24
Gabriela Chiosis, Seth McNutt, Tanaya Roychowdhury, Chiranjeevi Pasala, Hieu Nguyen, Daniel Thorton, Sahil Sharma, Luke Boticelli, Chander Digwal, Suhasini Joshi, Nan Yang, Palak Panchal, Souparna Chakrabarty, Sadik Bay, Vladimir Markov, Charlene Kwong, Jeanine Lisanti, Sun Young Chung, Stephen Ginsberg, Pengrong Yan, Elisa de Stanchina, Adriana Corben, Shanu Modi, Mary Alpaugh, Giorgio Colombo, Hediye Erdjument-Bromage, Thomas Neubert, Robert Chalkley, Peter Baker, Alma Burlingame, Anna Rodina, Feixia Chu
The intricate protein-chaperone network is vital for cellular function. Recent discoveries have unveiled the existence of specialized chaperone complexes called epichaperomes, protein assemblies orchestrating the reconfiguration of protein-protein interaction networks, enhancing cellular adaptability and proliferation. This study delves into the structural and regulatory aspects of epichaperomes, with a particular emphasis on the significance of post-translational modifications in shaping their formation and function...
April 3, 2024: Research Square
#25
Claire D James, Rachel L Lewis, Alexis L Fakunmoju, Austin J Witt, Aya H Youssef, Xu Wang, Nabiha M Rais, Apurva Tadimari Prabhakar, Raymonde Otoa, Molly L Bristol
UNLABELLED: Currently, there are no specific antiviral therapeutic approaches targeting Human papillomaviruses (HPVs), which cause around 5% of all human cancers. Specific antiviral reagents are particularly needed for HPV-related oropharyngeal cancers (HPV + OPCs) whose incidence is increasing and for which there are no early diagnostic tools available. We and others have demonstrated that the estrogen receptor alpha (ERα) is overexpressed in HPV + OPCs, compared to HPV-negative cancers in this region, and that these elevated levels are associated with an improved disease outcome...
April 12, 2024: bioRxiv
#26
Delta Ghoshal, Ingrid Petersen, Rachel Ringquist, Liana Kramer, Eshant Bhatia, Thomas Hu, Ariane Richard, Reda Park, Jenna Corbin, Savi Agarwal, Abel Thomas, Sebastian Ramirez, Jacob Tharayil, Emma Downey, Frank Ketchum, Abigail Ochal, Neha Sonthi, Sagar Lonial, James N Kochenderfer, Reginald Tran, Mandy Zhu, Wilbur A Lam, Ahmet F Coskun, Krishnendu Roy
UNLABELLED: Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment. Yet, it is unclear which BM niches give rise to MM pathophysiology. Here, we present a 3D microvascularized culture system, which models the endosteal and perivascular bone marrow niches, allowing us to study MM-stroma interactions in the BM niche and model responses to therapeutic CAR-T cells...
April 12, 2024: bioRxiv
#27
JOURNAL ARTICLE
Guo Zhao, Yuning Wang, Jiawei Zhou, Peiwen Ma, Shuhang Wang, Ning Li
BACKGROUND: Polo-like kinases (PLKs) are a kinase class of serine/threonine with five members that play crucial roles in cell cycle regulation. However, their biological functions, regulation, and expression remain unclear. This study revealed the molecular properties, oncogenic role, and clinical significance of PLK genes in pan-cancers, particularly in kidney renal papillary cell carcinoma (KIRP). METHODS: We evaluated the mutation landscape, expression level, and prognostic values of PLK genes using bioinformatics analyses and explored the association between the expression level of PLK genes and tumor microenvironment (TME), immune subtype, cancer immunotherapy, tumor stemness, and drug sensitivity...
April 30, 2024: Heliyon
#28
JOURNAL ARTICLE
Jiejun Zhou, Kun Zhang, Tian Yang, Anqi Li, Meng Li, Xiaojing Peng, Mingwei Chen
BACKGROUND: The role of glycosyltransferase (GT) genes in lung adenocarcinoma (LUAD) needs further elucidation. Thus, our study aims to identify the prognostic gene signature of LUAD and explore its molecular functions. METHODS: We initially extracted GT gene sets from the database, and obtained mRNA expression levels and clinical data from The Cancer Genome Atlas (TCGA) database. For constructing a prognostic model for GT genes, we utilized univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses...
April 30, 2024: Heliyon
#29
JOURNAL ARTICLE
Ottavia De Simoni, Melania Scarpa, Ignazio Castagliuolo, Astghik Stepanyan, Imerio Angriman, Andromachi Kotsafti, Camilla Nacci, Federico Scognamiglio, Silvia Negro, Antonella D'Angelo, Valentina Chiminazzo, Gianluca Businello, Cesare Ruffolo, Roberta Salmaso, Boris Franzato, Mario Gruppo, Pierluigi Pilati, Antonio Scapinello, Anna Pozza, Tommaso Stecca, Marco Massani, Ivana Cataldo, Stefano Brignola, Angelo Paolo Dei Tos, Carlotta Ceccon, Vincenza Guzzardo, Chiara Vignotto, Luca Facci, Isacco Maretto, Marco Agostini, Francesco Marchegiani, Giulia Becherucci, Maurizio Zizzo, Giovanni Bordignon, Roberto Merenda, Giovanni Pirozzolo, Alfonso Recordare, Giulia Pozza, Mario Godina, Isabella Mondi, Daunia Verdi, Corrado Da Lio, Licia Laurino, Luca Saadeh, Giorgio Rivella, Silvio Guerriero, Chiara Romiti, Giuseppe Portale, Chiara Cipollari, Ylenia Camilla Spolverato, Giulia Noaro, Roberto Cola, Salvatore Candioli, Laura Gavagna, Fabio Ricagna, Monica Ortenzi, Mario Guerrieri, Giovanni Tagliente, Monica Tomassi, Umberto Tedeschi, Beatrice Salmaso, Gianluca Buzzi, Dario Parini, Daniela Prando, Matteo Zuin, Francesca Bergamo, Vittorina Zagonel, Andrea Porzionato, Francesco Cavallin, Barbara Di Camillo, Loretta Di Cristoforo, Quoc Riccardo Bao, Salvatore Pucciarelli, Romeo Bardini, Gaya Spolverato, Matteo Fassan, Marco Scarpa
BACKGROUND: Long-term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer. METHODS: Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance-related genes (PD-L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus-deposited public database (GSE76583)...
April 22, 2024: Cancer
#30
REVIEW
Wenqing Jia, Xiaonan Shen, Zichao Guo, Xi Cheng, Ren Zhao
INTRODUCTION: Colorectal cancer (CRC) is the second most lethal malignancy worldwide. Immune checkpoint inhibitors (ICIs) benefit only 15% of patients with mismatch repair-deficient/microsatellite instability (dMMR/MSI) CRC. The majority of patients are not suitable due to insufficient immune infiltration. Cancer vaccines are a potential approach for inducing tumor-specific immunity within the solid tumor microenvironment. AREA COVERED: In this review, we have provided an overview of the current progress in CRC vaccines over the past three years and briefly depict promising directions for further exploration...
April 21, 2024: Expert Opinion on Biological Therapy
#31
REVIEW
Xiaoxia Xue, Xiangpeng Wang, Mingshi Pang, Liuchunyang Yu, Jinxiu Qian, Xiaoyu Li, Meng Tian, Cheng Lu, Cheng Xiao, Yuanyan Liu
Tumors desmoplastic microenvironments are characterized by abundant stromal cells and extracellular matrix (ECM) deposition. Cancer-associated fibroblasts (CAFs), as the most abundant of all stromal cells, play significant role in mediating microenvironments, which not only remodel ECM to establish unique pathological barriers to hinder drug delivery in desmoplastic tumors, but also talk with immune cells and cancer cells to promote immunosuppression and cancer stem cells-mediated drug resistance. Thus, CAFs mediated desmoplastic microenvironments will be emerging as promising strategy to treat desmoplastic tumors...
April 21, 2024: Journal of Nanobiotechnology
#32
JOURNAL ARTICLE
Yao Qin, Zhiyuan Li, Ting Liu, Jingjing Ma, Hong Liu, Yifan Zhou, Shuai Wang, Lei Zhang, Qiao Peng, Pei Ye, Ning Duan, Wenmei Wang, Xiang Wang
PURPOSE: Periodontitis-associated bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are closely linked to the risk of oral squamous cell carcinoma (OSCC). Emerging studies have indicated that another common periodontal pathogen, Prevotella intermedia (P. intermedia), is enriched in OSCC and could affect the occurrence and progression of OSCC. Our aim is to determine the effects of P. intermedia on the progression of OSCC and the role of antibiotics in reversing these effects...
April 21, 2024: Journal of Cancer Research and Clinical Oncology
#33
JOURNAL ARTICLE
Minyao Zhao, Yue Yu, Zhengyu Song
Uveal melanoma (UVM) is the most common primary tumor in adult human eyes. Costimulatory molecules (CMs) are important in maintaining T cell biological functions and regulating immune responses. To investigate the role of CMs in UVM and exploit prognostic signature by bioinformatics analysis. This study aimed to identify and validate a CMs associated signature and investigate its role in the progression and prognosis of UVM. The expression profile data of training cohort and validation cohort were downloaded from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) dataset...
April 21, 2024: Scientific Reports
#34
JOURNAL ARTICLE
Xiyang Ge, Yiyan Yin, Xiaoni Wang, Yixuan Gao, Xiaowen Guan, Jianghui Sun, Jin Ouyang, Na Na
Single-atom enzymes (SAzymes) exhibit great potential for chemodynamic therapy (CDT); while, general application is still challenged by their instability and unavoidable side effects during delivery. Herein, a manganese-based polyoxometalate single-atom enzyme (Mn-POM SAE) is first introduced into tumor-specific CDT, which exhibits tumor microenvironment (TME)-activated transition of nontoxicity-to-toxicity. Different from traditional POM materials, the aggregates of low-toxic Mn-POM SAE nanospheres are obtained at neutral conditions, facilitating efficient delivery and avoiding toxicity problems in normal tissues...
April 21, 2024: Small
#35
REVIEW
Sabina Pozzi, Ronit Satchi Fainaro
The communication between cells and their microenvironment represents an intrinsic and essential attribute that takes place in several biological processes, including tissue homeostasis and tissue repair. Among these interactions, inflammation is certainly a central biological response that occurs through cytokines and the crosstalk with their respective receptors. In particular, the interaction between CCL2 and its main receptor, CCR2, plays a pivotal role in both harmful and protective inflammatory states, including cancer-mediated inflammation...
April 19, 2024: Advanced Drug Delivery Reviews
#36
REVIEW
Zhenzhen Chen, Leaf Huang
The microbiome has emerged as a significant biomarker and modulator in cancer development and treatment response. Recent research highlights the notable role of Fusobacterium nucleatum (F. nucleatum) in various tumor types, including breast, colorectal, esophageal, gastric, pancreatic, and lung cancers. Accumulating evidence suggests that the local microbial community forms an integral component of the tumor microenvironment, with bacterial communities within tumors displaying specificity to tumor types. Mechanistic investigations indicate that tumor-associated microbiota can directly influence tumor initiation, progression, and responses to chemotherapy or immunotherapy...
April 19, 2024: Advanced Drug Delivery Reviews
#37
JOURNAL ARTICLE
V P Snijesh, Vidya P Nimbalkar, Sharada Patil, Savitha Rajarajan, C E Anupama, S Mahalakshmi, Annie Alexander, Ramu Soundharya, Rakesh Ramesh, B S Srinath, Mohit Kumar Jolly, Jyothi S Prabhu
BACKGROUND: The glucocorticoid receptor (GR) is frequently expressed in breast cancer (BC), and its prognostic implications are contingent on estrogen receptor (ER) status. To address conflicting reports and explore therapeutic potential, a GR signature (GRsig) independent of ER status was developed. We also investigated cell type-specific GR protein expression in BC tumor epithelial cells and infiltrating lymphocytes. METHODS: GRsig was derived from Dexamethasone treated cell lines through a bioinformatic pipeline...
April 20, 2024: Translational Oncology
#38
JOURNAL ARTICLE
Zucheng Xie, Yan Qin, Xinrui Chen, Sheng Yang, Jianliang Yang, Lin Gui, Peng Liu, Xiaohui He, Shengyu Zhou, Changgong Zhang, Le Tang, Yuankai Shi
BACKGROUND: The clinical and genetic characteristics, as well as treatment outcomes, of diffuse large B-cell lymphoma (DLBCL) patients with different MYD88 and CD79B mutation status merit further investigation. OBJECTIVE: This study aims to investigate the distinctions in clinical manifestations, genetic characteristics, and treatment outcomes among MYD88-CD79Bco-mut , MYD88/CD79Bsingle-mut , and MYD88-CD79Bco-wt DLBCL patients. PATIENTS AND METHODS: Clinical and genetic characteristics, along with treatment outcomes among 2696 DLBCL patients bearing MYD88-CD79Bco-mut , MYD88/CD79Bsingle-mut , and MYD88-CD79Bco-wt treated with R-CHOP/R-CHOP-like regimens from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and six external cohorts were analyzed...
April 21, 2024: Targeted Oncology
#39
JOURNAL ARTICLE
Chaojun Zhu, Lan Teng, Yihong Lai, Xingxing Yao, Yuxin Fang, Zihuan Wang, Simin Lin, Haonan Zhang, Qingyuan Li, Ye Li, Jianqun Cai, Yue Zhang, Changjie Wu, Bing Huang, Aimin Li, Side Liu, Qiuhua Lai
Peritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy. However, the molecular characteristics and pathogenesis of CRC peritoneal metastasis are poorly understood. Here, we aimed to elucidate the action and mechanism of adipose-derived stem cells (ADSCs), a prominent component of the peritoneal microenvironment, in CRC peritoneal metastasis formation. Database analysis indicated that ADSCs infiltration was increased in CRC peritoneal metastases, and high expression levels of ADSCs marker genes predicted a poor prognosis...
April 21, 2024: Cellular and Molecular Life Sciences: CMLS
#40
JOURNAL ARTICLE
Huan Liang, Chunchen Xu, Daoxia Guo, Fei Peng, Nan Chen, Haiyun Song, Xiaoyuan Ji
Therapy-induced immunogenic cell death (ICD) can initiate both innate and adaptive immune responses for amplified anti-tumor efficacy. However, dying cell-released ICD signals are prone to being sequestered by the TIM-3 receptors on dendritic cell (DC) surfaces, preventing immune surveillance. Herein, dismantlable coronated nanoparticles (NPs) are fabricated as a type of spatiotemporally controlled nanocarriers for coupling tumor cell-mediated ICD induction to DC-mediated immune sensing. These NPs are loaded with an ICD inducer, mitoxantrone (MTO), and wrapped by a redox-labile anti-TIM-3 (αTIM-3) antibody corona, forming a separable core-shell structure...
April 21, 2024: Advanced Materials
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