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Drug Discoveries & Therapeutics Sep 2023Gallbladder cancer (GBC) is a highly aggressive malignancy, which poses significant challenges for timely diagnosis, resulting in a dismal prognosis. Chemotherapy serves... (Review)
Review
Gallbladder cancer (GBC) is a highly aggressive malignancy, which poses significant challenges for timely diagnosis, resulting in a dismal prognosis. Chemotherapy serves as a primary treatment option in cases where surgery is not feasible. However, the emergence of chemoresistance poses a significant challenge to the effectiveness of chemotherapy, ultimately resulting in a poor prognosis. Despite extensive research on mechanisms of chemotherapeutic resistance in oncology, the underlying mechanisms of chemoresistance in GBC remain poorly understood. In this review, we present the findings from the last decade on the molecular mechanisms of chemotherapeutic resistance in GBC. We hope that these insights may provide novel therapeutic and experimental targets for further investigations into this lethal disease.
Topics: Humans; Gallbladder Neoplasms; Drug Resistance
PubMed: 37587052
DOI: 10.5582/ddt.2023.01013 -
Current Opinion in Microbiology Oct 2023Antibiotic-resistant microbe-mediated deaths are a major worldwide health issue. Unfortunately, due to microbial adaptation to develop resistance, some antibiotics are... (Review)
Review
Antibiotic-resistant microbe-mediated deaths are a major worldwide health issue. Unfortunately, due to microbial adaptation to develop resistance, some antibiotics are nullified early in their usage, and worse, resistance is detected before they can even be prescribed. Copper's toxicity since antiquity against microbes at the host-pathogen interface offers a fascinating weapon to fight antimicrobial resistance. Here, we briefly review why copper is so effective, how drugs that work with copper are effective antimicrobials, and how compounds such as these could reinvigorate investment in antimicrobial development.
Topics: Copper; Ionophores; Drug Resistance, Bacterial; Anti-Infective Agents; Anti-Bacterial Agents
PubMed: 37406562
DOI: 10.1016/j.mib.2023.102355 -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Helicobacter Infections; Helicobacter pylori; Anti-Bacterial Agents; Gastritis; Drug Resistance, Microbial
PubMed: 37850053
DOI: 10.3389/fcimb.2023.1296784 -
Trends in Cancer Nov 2023During tumor progression, mechanical abnormalities in the tumor microenvironment (TME) trigger signaling pathways in cells that activate cellular programs, resulting in... (Review)
Review
During tumor progression, mechanical abnormalities in the tumor microenvironment (TME) trigger signaling pathways in cells that activate cellular programs, resulting in tumor growth and drug resistance. In this review, we describe mechanisms of action for anti-cancer therapies and mechanotransduction programs that regulate cellular processes, including cell proliferation, apoptosis, survival and phenotype switching. We discuss how the therapeutic response is impacted by the three main mechanical TME abnormalities: high extracellular matrix (ECM) composition and stiffness; interstitial fluid pressure (IFP); and elevated mechanical forces. We also review drugs that normalize these abnormalities or block mechanosensors and mechanotransduction pathways. Finally, we discuss current challenges and perspectives for the development of new strategies targeting mechanically induced drug resistance in the clinic.
Topics: Humans; Mechanotransduction, Cellular; Neoplasms; Signal Transduction; Extracellular Matrix; Drug Resistance, Neoplasm; Tumor Microenvironment
PubMed: 37558577
DOI: 10.1016/j.trecan.2023.07.006 -
International Journal of Molecular... Aug 2023Biomechanical forces are of fundamental importance in biology, diseases, and medicine. Mechanobiology is an emerging interdisciplinary field that studies how biological... (Review)
Review
Biomechanical forces are of fundamental importance in biology, diseases, and medicine. Mechanobiology is an emerging interdisciplinary field that studies how biological mechanisms are regulated by biomechanical forces and how physical principles can be leveraged to innovate new therapeutic strategies. This article reviews state-of-the-art mechanobiology knowledge about the yes-associated protein (YAP), a key mechanosensitive protein, and its roles in the development of drug resistance in human cancer. Specifically, the article discusses three topics: how YAP is mechanically regulated in living cells; the molecular mechanobiology mechanisms by which YAP, along with other functional pathways, influences drug resistance of cancer cells (particularly lung cancer cells); and finally, how the mechanical regulation of YAP can influence drug resistance and vice versa. By integrating these topics, we present a unified framework that has the potential to bring theoretical insights into the design of novel mechanomedicines and advance next-generation cancer therapies to suppress tumor progression and metastasis.
Topics: Humans; Biomechanical Phenomena; Transcription Factors; Lung Neoplasms; Adaptor Proteins, Signal Transducing; Drug Resistance, Neoplasm
PubMed: 37569866
DOI: 10.3390/ijms241512491 -
Frontiers in Bioscience (Elite Edition) Jul 2023Infection diagnosis and antibiotic sensitivity testing are important aspects of clinical microbiology that are in dire need of improvement owing to the inadequate... (Review)
Review
Infection diagnosis and antibiotic sensitivity testing are important aspects of clinical microbiology that are in dire need of improvement owing to the inadequate current standards in the early detection of bacterial response to antibiotics. The increasing antimicrobial resistance is a serious global threat to human health. Current resistance-detecting methods, using the phenotypic antibiotic sensitivity test, which measures bacterial growth as affected by antibiotics, have long analysis times. Therefore, new and rapid methods are needed to detect antibiotic resistance. Here, we review the methods used to detect antibiotic resistance in bacteria, including that caused by biofilm development, and we look at the development of rapid methods for evaluating antimicrobial resistance (AMR).
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Biofilms
PubMed: 37743230
DOI: 10.31083/j.fbe1503019 -
NPJ Systems Biology and Applications Sep 2023Predicting evolution is a fundamental problem in biology with practical implications for treating antimicrobial resistance, which is a complex system-level phenomenon.... (Review)
Review
Predicting evolution is a fundamental problem in biology with practical implications for treating antimicrobial resistance, which is a complex system-level phenomenon. In this perspective article, we explore the limits of predicting antimicrobial resistance evolution, quantitatively define the predictability and repeatability of microevolutionary processes, and speculate on how these quantities vary across temporal, biological, and complexity scales. The opportunities and challenges for predicting antimicrobial resistance in the context of systems biology are also discussed. Based on recent research, we conclude that the evolution of antimicrobial resistance can be predicted using a systems biology approach integrating quantitative models with multiscale data from microbial evolution experiments.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial
PubMed: 37679446
DOI: 10.1038/s41540-023-00304-6 -
Advanced Science (Weinheim,... Sep 2023In recent years, the incidence of gastrointestinal cancers is increasing, particularly in the younger population. Effective treatment is crucial for improving patients'... (Review)
Review
In recent years, the incidence of gastrointestinal cancers is increasing, particularly in the younger population. Effective treatment is crucial for improving patients' survival outcomes. Programmed cell death, regulated by various genes, plays a fundamental role in the growth and development of organisms. It is also critical for maintaining tissue and organ homeostasis and takes part in multiple pathological processes. In addition to apoptosis, there are other types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, which can induce severe inflammatory responses. Notably, besides apoptosis, ferroptosis, necroptosis, and pyroptosis also contribute to the occurrence and development of gastrointestinal cancers. This review aims to provide a comprehensive summary on the biological roles and molecular mechanisms of ferroptosis, necroptosis, and pyroptosis, as well as their regulators in gastrointestinal cancers and hope to open up new paths for tumor targeted therapy in the near future.
Topics: Humans; Ferroptosis; Pyroptosis; Necroptosis; Gastrointestinal Neoplasms; Drug Resistance
PubMed: 37436087
DOI: 10.1002/advs.202300824 -
The Lancet. Planetary Health Jul 2023Social-ecological systems conceptualise how social human systems and ecological natural systems are intertwined. In this Personal View, we define the scope and... (Review)
Review
Social-ecological systems conceptualise how social human systems and ecological natural systems are intertwined. In this Personal View, we define the scope and applicability of social-ecological resilience to antimicrobial resistance. Resilience to antimicrobial resistance corresponds to the capacity to maintain the societal benefits of antimicrobial use and One Health systems' performance in the face of the evolutionary behaviour of microorganisms in response to antimicrobial use. Social-ecological resilience provides an appropriate framework to make sense of the disruptive impacts resulting from the emergence and spread of antimicrobial resistance; capture the diversity of strategies needed to tackle antimicrobial resistance and to live with it; understand the conditions that underpin the success or failure of interventions; and appreciate the need for adaptive and coevolutionary governance. Overall, resilience thinking is essential to improve understanding of how human societies dynamically can cope with, adapt, and transform to the growing global challenge of antimicrobial resistance.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Ecosystem
PubMed: 37438004
DOI: 10.1016/S2542-5196(23)00128-6 -
International Journal of Molecular... Dec 2023Trop-2 is a highly conserved one-pass transmembrane mammalian glycoprotein that is normally expressed in tissues such as the lung, intestines, and kidney during... (Review)
Review
Trop-2 is a highly conserved one-pass transmembrane mammalian glycoprotein that is normally expressed in tissues such as the lung, intestines, and kidney during embryonic development. It is overexpressed in many epithelial cancers but is absent in non-epithelial tumors. Trop-2 is an intracellular calcium signal transducer that participates in the promotion of cell proliferation, migration, invasion, metastasis, and probably stemness. It also has some tumor suppressor effects. The pro-tumoral actions have been thoroughly investigated and reported. However, Trop-2's activity in chemoresistance is less well known. We review a possible relationship between Trop-2, chemotherapy, and chemoresistance. We conclude that there is a clear role for Trop-2 in some specific chemoresistance events. On the other hand, there is no clear evidence for its participation in multidrug resistance through direct drug transport. The development of antibody conjugate drugs (ACD) centered on anti-Trop-2 monoclonal antibodies opened the gates for the treatment of some tumors resistant to classic chemotherapies. Advanced urothelial tumors and breast cancer were among the first malignancies for which these ACDs have been employed. However, there is a wide group of other tumors that may benefit from anti-Trop-2 therapy as soon as clinical trials are completed.
Topics: Female; Pregnancy; Animals; Drug Resistance, Neoplasm; Amyloidosis, Familial; Biological Transport; Calcium, Dietary; Cell Proliferation; Mammals
PubMed: 38203255
DOI: 10.3390/ijms25010087