Article
Oncology
Kavitha Yaddanapudi, Bryce F. Stamp, Priyanka B. Subrahmanyam, Andrei Smolenkov, Sabine J. Waigel, Rahul Gosain, Michael E. Egger, Robert C. G. Martin, Robert Buscaglia, Holden T. Maecker, Kelly M. McMasters, Jason A. Chesney
Summary: The study identified immunologic changes in the sentinel lymph nodes of melanoma patients that may impact melanoma treatment. These changes include a potential activation of immune response, as well as a decrease in NK cells and an increase in cells with low melanoma killing capabilities.
CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Andrew M. M. Hogan, A. S. M. Zisanur Rahman, Anna Motnenko, Aakash Natarajan, Dustin T. T. Maydaniuk, Beltina Leon, Zayra Batun, Armando Palacios, Alejandra Bosch, Silvia T. T. Cardona
Summary: This study systematically investigated the effects of antibiotics on the cell envelope of Burkholderia cepacia complex, and identified resistance and susceptibility determinants associated with the cell envelope. The findings provide insights into new drug targets and potential antibiotic combination strategies, which can contribute to improving antibacterial therapies.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Jian Lin, Yuting Dai, Chen Sang, Guohe Song, Bin Xiang, Mao Zhang, Liangqing Dong, Xiaoli Xia, Jiaqiang Ma, Xia Shen, Shuyi Ji, Shu Zhang, Mingjie Wang, Hai Fang, Xiaoming Zhang, Xiangdong Wang, Bing Zhang, Jian Zhou, Jia Fan, Hu Zhou, Daming Gao, Qiang Gao
Summary: This study reveals the heterogeneity of the immunogenomic traits in intrahepatic cholangiocarcinoma (iCCA) among patients, which poses challenges and opportunities for personalized immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Michelle M. Williams, Nicole S. Spoelstra, Spencer Arnesen, Kathleen O'Neill, Jessica L. Christenson, Jordan Reese, Kathleen C. Torkko, Andrew Goodspeed, Emmanuel Rosas, Toru Hanamura, Sharon B. Sams, Zheqi Li, Steffi Oesterreich, Rebecca B. Riggins, Britta M. Jacobsen, Anthony Elias, Jason Gertz, Jennifer K. Richer
Summary: Mutations in ESR1 are present in over 40% of metastatic breast cancers resistant to adjuvant aromatase inhibitor therapy, leading to constitutive estrogen receptor alpha activity. Metastatic lesions with mutant ER show increased levels of immune-suppressive macrophages, suggesting potential response to immunotherapies. Targeting proteins like AR and CHI3L1 in ER-mutant tumors may provide a therapeutic advantage in estrogen-deprived conditions.
Article
Chemistry, Multidisciplinary
Kaili Yang, Weijun Xiu, Yuqing Li, Dou Wang, Qirui Wen, Lihui Yuwen, Xiao Li, Zhaowei Yin, Bin Liang, Lianhui Wang
Summary: In this study, a near-infrared responsive 2D nanozyme was developed for efficient treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. The nanozyme exhibited effective antibacterial properties against MRSA through catalytic and photothermal effects. The results showed that the nanozyme had high bactericidal activity against MRSA under near-infrared light irradiation and promoted wound healing.
Article
Multidisciplinary Sciences
Xiaohong Xie, Lifeng Li, Liang Xie, Zhentian Liu, Guoliang Zhang, Xuan Gao, Wenying Peng, Haiyi Deng, Yilin Yang, Meiling Yang, Lianpeng Chang, Xin Yi, Xuefeng Xia, Zhiyi He, Chengzhi Zhou
Summary: EGFR-TKIs are effective in NSCLC patients with EGFR mutations but resistance often develops within a year. We developed an EGFR-TKIs resistance prediction model and validated it in cell lines, mice, and patient cohorts. The model successfully identified resistant cells, mice, and patients with shorter relapse time. The glycolysis pathway and KRAS upregulation were found to be related to EGFR-TKIs resistance, and MDSC played a role in immunosuppression in the resistant microenvironment.
Article
Medicine, General & Internal
Mieszko Lachota, Katarzyna Zielniok, Daniel Palacios, Minoru Kanaya, Leena Peena, Hanna Julie Hoel, Merete Thune Wiiger, Lise Kveberg, Wojciech Hautz, Radoslaw Zagozdzon, Karl-Johan Malmberg
Summary: Research has found that the chemokine receptor repertoire of peripheral blood NK cells changes during NK cell differentiation and is closely associated with the migratory response of different NK cell subsets. Simultaneous stimulation of CXCR1/2 and CX3CR1 receptors can synergistically enhance the migratory response of NK cells. The lack of naturally occurring chemokine-chemokine receptor pairs in human cancers may explain the exclusion of NK cells from the tumor microenvironment.
Article
Biochemistry & Molecular Biology
Maria Russo, Carmela Spagnuolo, Stefania Moccia, Idolo Tedesco, Fabio Lauria, Gian Luigi Russo
Summary: Cancer is a major cause of death worldwide. Resistance to chemo- and radiotherapy is a common hurdle in cancer treatment. This study investigated the role of cellular senescence in radiotherapy resistance and demonstrated that senolytic agents can enhance the effectiveness of radiotherapy in killing cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Infectious Diseases
Sriram Kk, Tsegaye Sewunet, Walaiporn Wangchinda, Teerawit Tangkoskul, Visanu Thamlikitkul, Christian G. Giske, Fredrik Westerlund
Summary: In this study, 27 CR-KP isolates from 16 patients were analyzed using NGS and ODM, with most isolates belonging to ST16. The plasmid carrying the bla(NDM-1) gene was identified in the ST16 isolates, and the potential of using ODM of plasmids as a marker for bacterial spread was highlighted. Additionally, ODM was able to differentiate between plasmids carrying different resistance genes in the ST16 isolates.
Article
Oncology
Gu Jin, Chunyang Wang, Dongdong Jia, Wenkang Qian, Chunming Yin, Danhua Wang, Quanyu Yang, Tao Li, Aiwen Zheng
Summary: This study provides insights into the genomic landscape of soft tissue sarcoma (STS) in Chinese patients, revealing TP53, MDM2, CDK4, and other genes as the most common mutation genes in this population. The identification of actionable mutations in a significant percentage of patients led to improved clinical outcomes for some individuals treated with corresponding molecular targeted therapies. These findings suggest the potential impact of NGS as a routine clinical test for guiding treatment decisions in patients with STS.
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
(2021)
Review
Oncology
Emanuela Grassilli, Maria Grazia Cerrito
Summary: Despite improvements in early diagnosis and treatment options for colorectal cancer, resistance to therapy remains a major challenge. Understanding the mechanisms of resistance allows for the development of novel therapeutic approaches to overcome it.
CANCER DRUG RESISTANCE
(2022)
Article
Medicine, General & Internal
Ioannis A. Voutsadakis
Summary: This study examined the BRAF and PIK3CA mutations in colorectal cancer cell lines and found similarities in molecular characteristics and clinical alterations. Potential targets for treatment were discovered through vulnerabilities and dependencies identified in these cell lines.
MEDICINA-LITHUANIA
(2022)
Article
Chemistry, Medicinal
Maytham Hussein, Rafah Allobawi, Jinxin Zhao, Heidi Yu, Stephanie L. Neville, Jonathan Wilksch, Labell J. M. Wong, Mark Baker, Christopher A. McDevitt, Gauri G. Rao, Jian Li, Tony Velkov
Summary: This study employed integrated metabolomics and transcriptomics methods to investigate the molecular mechanisms of ceftazidime/avibactam against a pan-drug-resistant K. pneumoniae clinical isolate. The study found that ceftazidime/avibactam induced time-dependent perturbations in the bacterium's metabolome and transcriptome, with notable effects at 6 hours. Ceftazidime/avibactam affected cell envelope biogenesis and central carbon metabolism, providing insights into the antibacterial and resistance mechanisms of the antibiotic.
ACS INFECTIOUS DISEASES
(2023)
Article
Neurosciences
Sara Lorio, Jan Sedlacik, Po-Wah So, Harold G. Parkes, Roxana Gunny, Ulrike Lobel, Yao-Feng Li, Olumide Ogunbiyi, Talisa Mistry, Emma Dixon, Sophie Adler, J. Helen Cross, Torsten Baldeweg, Thomas S. Jacques, Karin Shmueli, David W. Carmichael
Summary: This study investigated cortical tissue alterations in children with focal epilepsy using QSM technique, revealing that reductions in susceptibility in FCDIIb lesions were associated with changes in iron and calcium content. QSM improved lesion visibility compared to traditional imaging methods, and age-related changes in brain regions were observed as expected.
Article
Oncology
Joroen H. A. Creemers, Maarten J. van der Doelen, Sandra van Wilpe, Rick Hermsen, Tjitske Duiveman-de Boer, Diederik M. Somford, Marcel J. R. Janssen, J. P. Michiel Sedelaar, Niven Mehra, Johannes Textor, Harm Westdorp
Summary: Immune cell subsets in mCRPC patients changed during radium-223 therapy, with decreased absolute lymphocyte counts and increased expression of checkpoint molecules in T cells. The immunosuppressive subsets, including regulatory T cells and monocytic MDSCs, also increased throughout treatment. Further research is needed to explore the potential immunological consequences of these changes.
FRONTIERS IN ONCOLOGY
(2021)
Article
Genetics & Heredity
Hailing Yin, Rui Peng, Zhongzhong Chen, Hongyan Wang, Ting Zhang, Yufang Zheng
JOURNAL OF HUMAN GENETICS
(2020)
Article
Genetics & Heredity
Zhongzhong Chen, Xiaoling Lin, Yaping Wang, Hua Xie, Fang Chen
MOLECULAR GENETICS & GENOMIC MEDICINE
(2020)
Article
Pharmacology & Pharmacy
Soheila Kazemi, Shinsaku Kawaguchi, Christian E. Badr, Daphne R. Mattos, Ana Ruiz-Saenz, Jeffrey D. Serrill, Mark M. Moasser, Brian P. Dolan, Ville O. Paavilainen, Shinya Oishi, Kerry L. McPhail, Jane E. Ishmael
Summary: Coibamide A is a potent inhibitor of HER/ErbB signaling, particularly sensitive to HER3 and EGFR. It can decrease HER2 expression through Sec61-dependent inhibition, and enhance the cytotoxic efficacy of small molecule kinase inhibitors in breast and lung cancer cells.
BIOCHEMICAL PHARMACOLOGY
(2021)
Letter
Urology & Nephrology
Zhongzhong Chen, Hua Xie, Fang Chen
Article
Oncology
Ana Ruiz-Saenz, Farima Zahedi, Elliott Peterson, Ashley Yoo, Courtney A. Dreyer, Danislav S. Spassov, Juan Oses-Prieto, Alma Burlingame, Mark M. Moasser
Summary: The study examines the alterations of Src family kinases in cancer, revealing a decrease in S17 phosphorylation in the unstructured N-terminal unique domain of Src in cancer cells, potentially leading to increased Src dimerization. A deeper understanding of proteomic-level alterations in the unstructured UD of SFKs may offer significant insights into the deregulation of SFKs in cancers.
MOLECULAR CANCER RESEARCH
(2021)
Article
Cell Biology
Marcia R. Campbell, Ana Ruiz-Saenz, Elliott Peterson, Christopher Agnew, Pelin Ayaz, Sam Garfinkle, Peter Littlefield, Veronica Steri, Julie Oeffinger, Maryjo Sampang, Yibing Shan, David E. Shaw, Natalia Jura, Mark M. Moasser
Summary: This study investigated the structure-function relationship of HER2-HER3 signaling and identified potential target sites. The ATP binding and conformational coupling between the ATP pocket and the AP-2 pocket of HER3 were found to be critical for tumorigenic signaling and could be targeted.
Article
Cell Biology
Marcia R. Campbell, Ana Ruiz-Saenz, Yuntian Zhang, Elliott Peterson, Veronica Steri, Julie Oeffinger, Maryjo Sampang, Natalia Jura, Mark M. Moasser
Summary: This article presents an extensive structure-function analysis of HER2 and HER3 signaling in cancer treatment. It reveals that the extracellular domains (ECDs) of these receptors are not essential for tumorigenic signaling and their conformational changes do not affect the dimerization interface. Additionally, disruptive receptor engineering fails to disturb tumorigenic signaling. The overexpression of HER2 uncouples intracellular signaling from extracellular constraints.
Article
Endocrinology & Metabolism
Xiaohui Tao, Li Liu, Xingguang Yang, Zhe Wei, Zhongzhong Chen, Ge Zhang, Zhenlin Zhang, Hua Yue
Summary: This study evaluated the clinical features of sporadic Paget's disease of bone (PDB) in China and identified potential genetic abnormalities. The results showed that Chinese patients have an earlier onset age, more severe symptoms, and a lower frequency of SQSTM1 gene mutation compared to Western patients. Additionally, potential pathogenic genes and pathways related to neurodegeneration and ALS were identified.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Obstetrics & Gynecology
Zhong-Zhong Chen, Yun-Qian Gao, Hua Xiel, Yi-Chen Huang, Fang Chen, Yun-Ping Lei
Summary: This study investigates the roles of transcription factors (TFs) in the etiology of complex human birth defects, including neural tube defects (NTDs), congenital heart diseases (CHDs), and hypospadias. The study finds that TF genes are significantly enriched in complex birth defects and different gene expression profiles can distinguish different types of defects. The study indicates that abnormal expression patterns of specific TFs may disrupt the normal requirements for developmental equilibrium through related biological processes (BPs).
REPRODUCTIVE AND DEVELOPMENTAL MEDICINE
(2022)
Correction
Cell Biology
Marcia R. Campbell, Ana Ruiz-Saenz, Yuntian Zhang, Elliott Peterson, Veronica Steri, Julie Oeffinger, Maryjo Sampang, Natalia Jura, Mark M. Moasser
Article
Multidisciplinary Sciences
Zhongzhong Chen, Yunping Lei, Richard H. Finnell, Yu Ding, Zhixi Su, Yaping Wang, Hua Xie, Fang Chen
Summary: Through whole exome sequencing, we identified NR5A1, SRD5A2, and AR as mutational hot-spots in severe hypospadias, and cilia-related outer dynein arm heavy chain (ODNAH) genes as significantly enriched in hypospadias. The Dnah8 KO mice displayed disrupted testosterone levels and urethral development, linking ciliary genes with hypospadias. The identification of ODNAH genes with rare damaging variants provides significant insights into the genetic basis and genetic counseling of hypospadias.
Article
Oncology
Ana Ruiz-Saenz, Chloe E. Atreya, Changjun Wang, Bo Pan, Courtney A. Dreyer, Diede Brunen, Anirudh Prahallad, Denise P. Munoz, Dana J. Ramms, Valeria Burghi, Danislav S. Spassov, Eleanor Fewings, Yeonjoo C. Hwang, Cynthia Cowdrey, Christina Moelders, Cecilia Schwarzer, Denise M. Wolf, Byron Hann, Scott R. VandenBerg, Kevan Shokat, Mark M. Moasser, Rene Bernards, J. Silvio Gutkind, Laura J. van 't Veer, Jean-Philippe Coppe
Summary: Coppe and colleagues discover a resistance mechanism in BRAF(V600E) colorectal cancers that can be overcome with COX2 inhibitors. SRC kinases play a role in resistance to BRAF/EGFR-targeted therapy and can be effectively targeted in combination with BRAF and EGFR. Compensatory activation of SRC kinases is mediated by an autocrine prostaglandin E-2 loop, which can be blocked with COX2 inhibitors. Co-targeting COX2, BRAF, and EGFR promotes long-lasting suppression of tumor growth in patient-derived tumor xenograft models.
Article
Cell Biology
Rui Zhao, Li Cao, Wen-Jun Gu, Lei Li, Zhong-Zhong Chen, Jie Xiang, Ze-Yu Zhou, Bo Xu, Wei-Dong Zang, Xiang-Yu Zhou, Jing Cao, Kun Sun, Jian-Yuan Zhao
Summary: Research has shown that dysregulated maternal fatty acid metabolism increases the risk of congenital heart disease (CHD) in offspring, but the exact mechanism is unknown. Additionally, the efficacy of folic acid fortification in preventing CHD is controversial. In this study, using GC-FID/MS analysis, the researchers found that pregnant women carrying children with CHD had significantly increased levels of palmitic acid (PA) in their serum samples. Feeding pregnant mice with PA increased the risk of CHD in their offspring, and folic acid supplementation did not rescue this effect.
CELL REPORTS MEDICINE
(2023)
Article
Biochemical Research Methods
Roos Vincken, Ana Ruiz-Saenz
Summary: Current protocols for measuring antibody-dependent cellular cytotoxicity (ADCC) in vitro using peripheral blood mononuclear cells (PBMCs) suffer from isolation and variability issues among donors, impeding viability and reproducibility. This study presents a standardized co-culture model system to quantify ADCC on human breast cancer cells. The engineered natural killer cell line expressing FCgRIIIa (CD16) and the subsequent cancer-immune co-culture setup, cytotoxicity measurement, and analysis are described.
Meeting Abstract
Oncology
Chloe E. Atreya, Ana Ruiz-Saenz, Changjun Wang, Bo Pan, Courtney A. Dreyer, Diede Brunen, Anirudh Prahallad, Danislav Spassov, Dana J. Steffen, Byron C. Hann, Scott R. VandenBerg, Silvio Gutkind, Mark M. Moasser, Laura J. van't Veer, Jean-Philippe Coppe
MOLECULAR CANCER THERAPEUTICS
(2019)
