Article
Chemistry, Analytical
Han Li, Jiaojiao Li, Meng Wang, Weiyue Feng, Fuping Gao, Ying Han, Yijie Shi, Zhongying Du, Qing Yuan, Peng Cao, Xiayan Wang, Xueyun Gao, Kai Cao, Liang Gao
Summary: Identifying effective reversal agents to overcome multidrug resistance is crucial for improving tumor chemotherapy. In this study, a metal cluster-based probe called clusterbody was developed for flow sorting-assisted single-cell mass spectrometry analysis. The clusterbody, synthesized through biomimetic mineralization, selectively recognizes an efflux pump protein and enables high-throughput cell sorting based on fluorescence emitted by the probe. Protein abundance at the single-cell level is determined through precise signal amplification using laser ablation inductively coupled plasma mass spectrometry, allowing quantitative evaluation of reversal agent treatment. This work provides a new approach to identify reversal agents and sheds light on developing combined or synergetic tumor therapy.
ANALYTICAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Suman Panda, Oishika Chatterjee, Laboni Roy, Subhrangsu Chatterjee
Summary: This review discusses the involvement of calcium signaling in cancer progression and multidrug resistance, as well as the possibilities and challenges of targeting calcium channels, transporters, and pumps for cancer treatment through structure-based drug design.
DRUG DISCOVERY TODAY
(2022)
Review
Biochemistry & Molecular Biology
Tingting Liang, Lu Lu, Xueting Song, Jianguo Qi, Jianhong Wang
Summary: This article reviews the combinations of microtubule targeting agents (MTAs) with other anticancer drugs to overcome toxicities, resistance, and improve treatment efficacy for cancer. It provides helpful information for combination therapy based on MTAs.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Chemistry, Multidisciplinary
Jing Wang, Liangbo Hu, Hongyue Zhang, Yu Fang, Tingliang Wang, Huaimin Wang
Summary: Biomolecular condensates play a crucial role in controlling cellular functions, but constructing artificial biomolecular condensates remains challenging. This study presents a general approach to construct biomolecular condensates in lysosomes of living cells for cancer therapy, with potential applications in addressing multiple drug resistance.
ADVANCED MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Wanhua Zhang, Linyu Yang, Wenting Si, Minghai Tang, Peng Bai, Zejiang Zhu, Shuang Kuang, Jiang Liu, Mingsong Shi, Jinxing Huang, Xuanming Chen, Dan Li, Yi Wen, Zhuang Yang, Kai Xiao, Lijuan Chen
Summary: In this study, a hydroxamic acid based microtubule-destabilizing agent (MDA), SKLB-14b, was discovered and showed potent anti-proliferative activity on a wide spectrum of human cancer cell lines. It exhibited good metabolic stability, high oral bioavailability, and inhibited tumor growth in both sensitive and resistant xenograft mouse models. Mechanistically, SKLB-14b exerted anti-tumor and anti-multidrug resistance effects through cell cycle arrest, pro-apoptotic activities, and vascular disrupting activities.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Ingrid Fatima Zattoni, Leticia Carani Delabio, Julia de Paula Dutra, Diogo Henrique Kita, Gustavo Scheiffer, Marina Hembecker, Giovana da Silva Pereira, Vivian Rotuno Moure, Glaucio Valdameri
Summary: The primary source of failure in cancer therapies is multidrug resistance (MDR) caused by overexpression of ABC transporters, particularly the breast cancer resistance protein (BCRP/ABCG2). Inhibiting ABCG2 function and modulating its expression are promising strategies to overcome MDR. This review provides an overview of various ABCG2 inhibitors and discusses their chemical aspects, experimental methods used for identification and characterization, as well as the biological requirements for preclinical tests. Additionally, the potential use of ABCG2 inhibitors in cancer stem cells (CSC) to improve treatment response and the mechanism of ABCG2 modulators at the transcriptional and protein expression levels are discussed.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Kaipei Luo, Feng Xu, Tianyi Yao, Jianping Zhu, Hua Yu, Guangji Wang, Juan Li
Summary: A dual-modified lipid albumin nanosystem was developed for targeted delivery of paclitaxel to treat multidrug-resistant cancer. The system showed improved intracellular accumulation of the drug and demonstrated excellent antitumor efficacy by inhibiting cell proliferation through controlled drug release within cells. In vivo studies confirmed elevated tumor accumulation and significant survival benefits in tumor-bearing mice, showcasing the potential of this system for targeted chemotherapy and overcoming multidrug resistance in cancer treatment.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Biochemistry & Molecular Biology
Bo Peng, Si-Yuan Zhang, Ka Iong Chan, Zhang-Feng Zhong, Yi-Tao Wang
Summary: Breast cancer is a common cancer in women worldwide, and the challenges in its treatment include abnormal metabolism, immunosuppression, and drug resistance. AMPK can regulate metabolic reprogramming, inhibit breast cancer cell growth and metastasis, and stimulate immune cell responses. However, the role of AMPK in breast cancer progression is still controversial.
Article
Chemistry, Medicinal
David S. P. Cardoso, Annamaria Kincses, Marta Nove, Gabriella Spengler, Silva Mulhovo, Joao Aires-de-Sousa, Daniel J. V. A. dos Santos, Maria-Jose U. Ferreira
Summary: This study aimed to enhance multidrug resistance (MDR) reversing activity in cancer by deriving new compounds from major epimeric alkaloids isolated from Tabernaemontana elegans. The derivatives showed increased activity, with those containing N-phenethyl moieties exhibiting the strongest P-glycoprotein inhibitory effects. Synergistic interactions with the antineoplastic drug doxorubicin were observed, highlighting the potential of these compounds as MDR reversers. Lipophilicity and bulkiness features were associated with inhibitory activity based on the explored QSAR models.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Mohsen Hemmati-Dinarvand, Hassan Ahmadvand, Atefeh Seghatoleslam
Summary: The study aimed to investigate the molecular mechanism of multidrug resistance (MDR) in LS174T and LS174T/Oxaliplatin (OXP) cell lines during treatment with Nitazoxanide (NTZ) in combination with OXP. The results showed that NTZ could reverse MDR by downregulating the Wnt/β-catenin signaling pathway, leading to increased sensitivity of colorectal cancer (CRC) cells to OXP-induced apoptosis and inhibition of cell proliferation.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Xiangyang Zhang, Min Wang, Junyi Feng, Bin Qin, Chenglin Zhang, Chengshen Zhu, Wentao Liu, Yaohe Wang, Wei Liu, Lei Huang, Shuangshuang Lu, Zhimin Wang
Summary: The development of multidrug resistance (MDR) in cancer chemotherapy is a major challenge. This study identified MVP and BCL2 as potential factors driving MDR in ESCC. A self-assembling nanoparticle platform was designed to deliver Adriamycin and siRNAs targeting MVP and BCL2, reducing drug efflux and promoting apoptosis. The nanoparticles effectively inhibited cancer cell growth and tumor development.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jun Ren, Zhiqing Hu, Gengming Niu, Jie Xia, Xing Wang, Runqi Hong, Jiawei Gu, Daorong Wang, Chongwei Ke
Summary: Resistance to oxaliplatin is a major cause of recurrence in gastric cancer patients. ANXA1 has been identified as a key regulator in the chemoresistance of gastric cancer cells to oxaliplatin by inhibiting autophagy. The PI3K/AKT/mTOR signaling pathway is activated in ANXA1 knockdown cells, leading to the suppression of autophagy.
Article
Pharmacology & Pharmacy
Yan-Bo Zheng, Yan-Qun Dong, Shu-Yi Si, Yong-Su Zhen, Jian-Hua Gong
Summary: IMB5476, a novel nitrobenzoate microtubule inhibitor, exhibits increased aqueous solubility. It disrupts microtubule networks in cells, causing cell cycle arrest and inducing cell death through mitotic catastrophe and apoptosis. IMB5476 also inhibits angiogenesis and overcomes multidrug resistance.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Gao-Jie Ye, Chao-Yun Cai, Zhuo-Xun Wu, Qiu-Xu Teng, Jing-Quan Wang, Zhe-Sheng Chen, Bo Wang
Summary: Three series of phenylurea indole derivatives were synthesized with potent inhibitory activities on ABCG2. Four phenylurea indole derivatives with extended 7C system showed the most potent ABCG2 inhibition and no inhibition on ABCB1. Further investigation on two compounds revealed that they increased the accumulation of mitoxantrone in ABCG2-overexpressing cells and stimulated the ATP hydrolysis of ABCG2 transporter.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Yanran Li, Zigui Wang, Yanxin Qi, Zhaohui Tang, Xiaoyuan Li, Yubin Huang
Summary: In this study, a Pt-IV prodrug that can be activated in a spatiotemporally controllable manner inside the mitochondria of cancer cells was designed. The prodrug effectively released cisplatin upon red light exposure, leading to increased cytotoxicity and accumulation in cancer cells. This work demonstrates the potential of controllably activated and mitochondrion-targeting Pt-IV prodrugs to overcome chemotherapy drug resistance.
CHEMICAL COMMUNICATIONS
(2022)
Editorial Material
Virology
Basil S. Karam, Rachel S. Morris, Carolyn T. Bramante, Michael Puskarich, Emily J. Zolfaghari, Sahar Lotfi-Emran, Nicholas E. Ingraham, Anthony Charles, David J. Odde, Christopher J. Tignanelli
Summary: The mTOR pathway plays a crucial role in viral infections, with inhibiting mTOR potentially leading to suppression of virus growth and replication. Recent studies suggest the modulation of mTOR in SARS-CoV-2 infection, highlighting the potential of mTOR inhibitors as an effective treatment for coronavirus diseases.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Engineering, Biomedical
Mahya Hemmat, David J. Odde
Summary: This study uses multiscale modeling to show that GTP hydrolysis results in both longitudinal bond weakening and an outward bending preference, which together drive microtubule dynamic instability and lead to the observed microtubule tip structures. This research demonstrates the use of atomic-level structural information as the sole input to predict cellular-level dynamics without parameter adjustment.
ANNALS OF BIOMEDICAL ENGINEERING
(2021)
Article
Chemistry, Medicinal
Bakar A. Hassan, Jozafina Milicaj, Carlos Andres Ramirez-Mondragon, Yuk Yin Sham, Erika A. Taylor
Summary: Understanding the dynamic motions and ligand recognition patterns of HepI can provide insights into the behavior of other GT-B enzymes. Molecular dynamics simulations and analysis of ligand binding energies suggest energetically favored enzymatic pathways for HepI.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Oncology
Kellen Mulford, Mariah McMahon, Andrew M. Gardeck, Matthew A. Hunt, Clark C. Chen, David J. Odde, Christopher Wilke
Summary: This study developed a non-invasive method to predict the motility of glioblastoma cells using radiomics features. It showed the feasibility of a quantitative MRI feature-based regression model in predicting the cellular motility of glioblastomas.
Article
Immunology
Carolyn T. Bramante, Jennifer L. Proper, David R. Boulware, Amy B. Karger, Thomas Murray, Via Rao, Aubrey Hagen, Christopher J. Tignanelli, Michael Puskarich, Ken Cohen, David M. Liebovitz, Nichole R. Klatt, Courtney Broedlow, Katrina M. Hartman, Jacinda Nicklas, Sherehan Ibrahim, Adnin Zaman, Hanna Saveraid, Hrishikesh Belani, Nicholas Ingraham, Grace Christensen, Lianne Siegel, Nancy E. Sherwood, Regina Fricton, Sam Lee, David J. Odde, John B. Buse, Jared D. Huling
Summary: This analysis compared baseline viral load and symptoms between vaccinated and unvaccinated adults. The results showed that vaccination within 6 months of infection was associated with a lower viral load and fewer systemic symptoms.
OPEN FORUM INFECTIOUS DISEASES
(2022)
Article
Chemistry, Multidisciplinary
Jozafina Milicaj, Vasudeva R. Dodda, Kaelan R. Patel, Ingrid Rodriguez Aragon, Timothy O'Connell, Ramaiah Muthyala, Erika A. Taylor, Yuk Y. Sham
Summary: Research has shown that using practical examples in undergraduate education can improve retention rates of historically underrepresented students in STEM majors and reduce achievement gaps. This study presents a laboratory experiment that translates medicinal chemistry synthesis into a method suitable for undergraduate labs, resulting in the successful synthesis of a clinically important drug and its analogues. The experiment introduces various concepts and analytical techniques, enhancing student learning in the field.
JOURNAL OF CHEMICAL EDUCATION
(2022)
Article
Multidisciplinary Sciences
Jozafina Milicaj, Bakar A. Hassan, Joy M. Cote, Carlos A. Ramirez-Mondragon, Nadiya Jaunbocus, Angelika Rafalowski, Kaelan R. Patel, Colleen D. Castro, Ramaiah Muthyala, Yuk Y. Sham, Erika A. Taylor
Summary: Aminoglycosides have been experimentally validated as nanomolar inhibitors of Heptosyltransferase I (HepI), suggesting an alternative mechanism of action for these antibiotics and potentially impacting their efficacy in fighting bacterial infections.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Bakar A. Hassan, Zhiqi A. Liu, Jozafina Milicaj, Mia S. Kim, Meka Tyson, Yuk Y. Sham, Erika A. Taylor
Summary: This study provides the first kinetic and biophysical characterization of HepII, revealing its shared properties with HepI, such as donor promiscuity and acceptor-induced structural changes. HepII exhibits higher catalytic efficiency and stronger binding affinity for substrates compared to HepI.
Article
Biochemistry & Molecular Biology
Sung Hoon Lee, Jay C. Hou, Archer Hamidzadeh, M. Sulaiman Yousafzai, Visar Ajeti, Hao Chang, David J. Odde, Michael Murrell, Andre Levchenko
Summary: This study reveals that cyclic changes in the activity of the small GTPase RhoA, mediated by the RhoA guanine nucleotide exchange factor GEF-H1 and triggered by an increase in intracellular Ca2+ levels, are responsible for navigation through a dense extracellular matrix during cell migration. The cyclic changes are driven by two coupled negative feedback loops dependent on microtubule dynamics. Additionally, an increasing frequency of the molecular clock leads to faster cell migration within physically confining spaces.
Article
Immunology
David R. Boulware, Thomas A. Murray, Jennifer L. Proper, Christopher J. Tignanelli, John B. Buse, David M. Liebovitz, Jacinda M. Nicklas, Kenneth Cohen, Michael A. Puskarich, Hrishikesh K. Belani, Lianne K. Siegel, Nichole R. Klatt, David J. Odde, Amy B. Karger, Nicholas E. Ingraham, Katrina M. Hartman, Via Rao, Aubrey A. Hagen, Barkha Patel, Sarah L. Fenno, Nandini Avula, Neha Reddy, Spencer M. Erickson, Sarah Lindberg, Regina Fricton, Samuel Lee, Adnin Zaman, Hanna G. Saveraid, Walker J. Tordsen, Matthew F. Pullen, Nancy E. Sherwood, Jared D. Huling, Carolyn T. Bramante
Summary: SARS-CoV-2 vaccine-boosted participants experienced the least severe symptoms during COVID-19, and their symptoms improved the fastest over time. Vaccination against SARS-CoV-2 was found to be associated with reduced symptom severity in a sample of low to moderate risk adults enrolled in an outpatient COVID-19 treatment trial. Booster shots further reduced symptom severity.
CLINICAL INFECTIOUS DISEASES
(2023)
Correction
Biochemistry & Molecular Biology
Bhavani S. Sahu, Megin E. Nguyen, Pedro Rodriguez, Jean Pierre Pallais, Vinayak Ghosh, Maria Razzoli, Yuk Y. Sham, Stephen R. Salton, Alessandro Bartolomucci
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Immunology
James D. Dahlvang, Jenna K. Dick, Jules A. Sangala, Philippa R. Kennedy, Emily J. Pomeroy, Kristin M. Snyder, Juliette M. Moushon, Claire E. Thefaine, Jianming Wu, Sara E. Hamilton, Martin Felices, Jeffrey S. Miller, Bruce Walcheck, Beau R. Webber, Branden S. Moriarity, Geoffrey T. Hart
Summary: CMV infection alters NK cell phenotype and function, resulting in the generation of adaptive NK cells with enhanced ADCC and cytokine production. The loss of SYK kinase, rather than the absence of FcRy or PLZF, is likely the main driver behind the increased cytotoxicity and cytokine production in adaptive NK cells.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Biophysics
Roberto Alonso-Matilla, Paolo P. Provenzano, David J. Odde
Summary: This study generalized the motor-clutch analytical framework to include imbalanced motor-clutch regimes, with clutch reinforcement and catch bonding, and investigated optimality with respect to all parameters. The results found that cells could tune their clutch mechanical properties to perform a specific function and could regulate their myosin repertoire and activity to maximize force transmission. In addition, the study revealed that clutch reinforcement shifted the optimum substrate stiffness to larger values. These findings have important implications for the design of molecular tension sensors and the prediction and control of cell adhesion and migration in immunotherapy and cancer.
BIOPHYSICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Asumi Hoshino, Valentino Clemente, Mihir Shetty, Brian Castle, David Odde, Martina Bazzaro
Summary: UNC-45A is an ATP-independent microtubule-severing protein that can induce microtubule curvature. It is enriched in curved areas of microtubules and its overexpression or depletion can alter microtubule curvature. Additionally, it is found that Paclitaxel can straighten microtubules and UNC-45A can counteract this effect.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Meeting Abstract
Oncology
B. C. Braman, G. A. Shamsan, M. M. McMahon, D. J. Odde, C. T. Wilke
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)