Pharmacology & Therapeutics最新文献

{"title":"Altered cancer metabolism and implications for next-generation CAR T-cell therapies","authors":"Rishab Ramapriyan ,&nbsp;Vivasvan S. Vykunta ,&nbsp;Gust Vandecandelaere ,&nbsp;Leland G.K. Richardson ,&nbsp;Jing Sun ,&nbsp;William T. Curry ,&nbsp;Bryan D. Choi","doi":"10.1016/j.pharmthera.2024.108667","DOIUrl":"10.1016/j.pharmthera.2024.108667","url":null,"abstract":"<div><p>This review critically examines the evolving landscape of chimeric antigen receptor (CAR) T-cell therapy in treating solid tumors, with a particular focus on the metabolic challenges within the tumor microenvironment. CAR T-cell therapy has demonstrated remarkable success in hematologic malignancies, yet its efficacy in solid tumors remains limited. A significant barrier is the hostile milieu of the tumor microenvironment, which impairs CAR T-cell survival and function. This review delves into the metabolic adaptations of cancer cells and their impact on immune cells, highlighting the competition for nutrients and the accumulation of immunosuppressive metabolites. It also explores emerging strategies to enhance CAR T-cell metabolic fitness and persistence, including genetic engineering and metabolic reprogramming. An integrated approach, combining metabolic interventions with CAR T-cell therapy, has the potential to overcome these constraints and improve therapeutic outcomes in solid tumors.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108667"},"PeriodicalIF":13.5,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141029508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALDH2 polymorphism and myocardial infarction: From alcohol metabolism to redox regulation","authors":"Reece J. Lamb ,&nbsp;Kayleigh Griffiths ,&nbsp;Gregory Y.H. Lip ,&nbsp;Vitaly Sorokin ,&nbsp;Michael P. Frenneaux ,&nbsp;Martin Feelisch ,&nbsp;Melanie Madhani","doi":"10.1016/j.pharmthera.2024.108666","DOIUrl":"10.1016/j.pharmthera.2024.108666","url":null,"abstract":"<div><p>Acute myocardial infarction (AMI) remains a leading cause of death worldwide. Increased formation of reactive oxygen species (ROS) during the early reperfusion phase is thought to trigger lipid peroxidation and disrupt redox homeostasis, leading to myocardial injury. Whilst the mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) is chiefly recognised for its central role in ethanol metabolism, substantial experimental evidence suggests an additional cardioprotective role for ALDH2 independent of alcohol intake, which mitigates myocardial injury by detoxifying breakdown products of lipid peroxidation including the reactive aldehydes, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Epidemiological evidence suggests that an ALDH2 mutant variant with reduced activity that is highly prevalent in the East Asian population increases AMI risk. Additional studies have uncovered a strong association between coronary heart disease and this ALDH2 mutant variant. It appears this enzyme polymorphism (in particular, in ALDH2*2/2 carriers) has the potential to have wide-ranging effects on thiol reactivity, redox tone and therefore numerous redox-related signaling processes, resilience of the heart to cope with lifestyle-related and environmental stressors, and the ability of the whole body to achieve redox balance. In this review, we summarize the journey of ALDH2 from a mitochondrial reductase linked to alcohol metabolism, <em>via</em> pre-clinical studies aimed at stimulating ALDH2 activity to reduce myocardial injury to clinical evidence for its protective role in the heart.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108666"},"PeriodicalIF":13.5,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016372582400086X/pdfft?md5=d1ecdcb6f90f4a15f49b7d911fd0e346&pid=1-s2.0-S016372582400086X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141036078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric analysis of research progress on tetramethylpyrazine and its effects on ischemia-reperfusion injury","authors":"Mingzhu Qi,&nbsp;Xiaohui Su,&nbsp;Zhuohang Li,&nbsp;Helan Huang,&nbsp;Jingbo Wang,&nbsp;Na Lin,&nbsp;Xiangying Kong","doi":"10.1016/j.pharmthera.2024.108656","DOIUrl":"10.1016/j.pharmthera.2024.108656","url":null,"abstract":"<div><p>In recent decades, natural products have attracted worldwide attention and become one of the most important resources for pharmacological industries and medical sciences to identify novel drug candidates for disease treatment. Tetramethylpyrazine (TMP) is an alkaloid extracted from <em>Ligusticum chuanxiong Hort.</em>, which has shown great therapeutic potential in cardiovascular and cerebrovascular diseases, liver and renal injury, as well as cancer. In this review, we analyzed 1270 papers published on the Web of Science Core Collection from 2002 to 2022 and found that TMP exerted significant protective effects on ischemia-reperfusion (I/R) injury that is the cause of pathological damages in a variety of conditions, such as ischemic stroke, myocardial infarction, acute kidney injury, and liver transplantation. TMP is limited in clinical applications to some extent due to its rapid metabolism, a short biological half-life and poor bioavailability. Obviously, the structural modification, administration methods and dosage forms of TMP need to be further investigated in order to improve its bioavailability. This review summarizes the clinical applications of TMP, elucidates its potential mechanisms in protecting I/R injury, provides strategies to improve bioavailability, which presents a comprehensive understanding of the important compound. Hopefully, the information and knowledge from this review can help researchers and physicians to better improve the applications of TMP in the clinic.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108656"},"PeriodicalIF":13.5,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical diversity, traditional uses, and bioactivities of Rosa roxburghii Tratt: A comprehensive review","authors":"Archana Jain ,&nbsp;Surendra Sarsaiya ,&nbsp;Qihai Gong ,&nbsp;Qin Wu ,&nbsp;Jingshan Shi","doi":"10.1016/j.pharmthera.2024.108657","DOIUrl":"10.1016/j.pharmthera.2024.108657","url":null,"abstract":"<div><p><em>Rosa roxburghii</em> Tratt (RRT), known as chestnut rose, has been a subject of growing interest because of its diverse chemical composition and wide range of traditional uses. This comprehensive review aimed to thoroughly examine RRT, including its traditional applications, chemical diversity, and various bioactivities. The chemical profile of this plant is characterized by the presence of essential nutrients such as vitamin C (ascorbic acid), flavonoids, triterpenes, organic acids, tannins, phenolic compounds, polysaccharides, carotenoids, triterpenoids, volatile compounds, amino acids, and essential oils. These constituents contribute to the medicinal and nutritional value. Additionally, we explore the multifaceted bioactivities of RRT, including its potential as an anticancer agent, antioxidant, antiaging agent, antiatherogenic agent, hypoglycemic agent, immunoregulatory modulator, radioprotective agent, antimutagenic agent, digestive system regulator, anti-inflammatory agent, cardioprotective agent, and antibacterial agent, and its intriguing role in modulating the gut microbiota. Furthermore, we discuss the geographical distribution and genetic diversity of this plant species and shed light on its ecological significance. This comprehensive review provides a holistic understanding of RRT, bridges traditional knowledge with contemporary scientific research, and highlights its potential applications in medicine, nutrition, and pharmacology.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108657"},"PeriodicalIF":13.5,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease progression modeling with temporal realignment: An emerging approach to deepen knowledge on chronic diseases","authors":"Hideki Yoshioka ,&nbsp;Ryota Jin ,&nbsp;Akihiro Hisaka ,&nbsp;Hiroshi Suzuki","doi":"10.1016/j.pharmthera.2024.108655","DOIUrl":"10.1016/j.pharmthera.2024.108655","url":null,"abstract":"<div><p>The recent development of the first disease-modifying drug for Alzheimer's disease represents a major advancement in dementia treatment. Behind this breakthrough is a quarter century of research efforts to understand the disease not by a particular symptom at a given moment, but by long-term sequential changes in multiple biomarkers. Disease progression modeling with temporal realignment (DPM-TR) is an emerging computational approach proposed with this biomarker-based disease concept. By integrating short-term clinical observations of multiple disease biomarkers in a data-driven manner, DPM-TR provides a way to understand the progression of chronic diseases over decades and predict individual disease stages more accurately. DPM-TR has been developed primarily in the area of neurodegenerative diseases but has recently been extended to non-neurodegenerative diseases, including chronic obstructive pulmonary, autoimmune, and ophthalmologic diseases. This review focuses on opportunities for DPM-TR in clinical practice and drug development and discusses its current status and challenges.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108655"},"PeriodicalIF":13.5,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of lidocaine in cancer progression and patient survival","authors":"Kohei Chida ,&nbsp;Hirofumi Kanazawa ,&nbsp;Hirotaka Kinoshita ,&nbsp;Arya Mariam Roy ,&nbsp;Kenichi Hakamada ,&nbsp;Kazuaki Takabe","doi":"10.1016/j.pharmthera.2024.108654","DOIUrl":"10.1016/j.pharmthera.2024.108654","url":null,"abstract":"<div><p>Since its development in 1943, lidocaine has been one of the most commonly used local anesthesia agents for surgical procedures. Lidocaine alters neuronal signal transmission by prolonging the inactivation of fast voltage-gated sodium channels in the cell membrane of neurons, which are responsible for action potential propagation. Recently, it has attracted attention due to emerging evidence suggesting its potential antitumor properties, particularly in the in vitro setting. Further, local administration of lidocaine around the tumor immediately prior to surgical removal has been shown to improve overall survival in breast cancer patients. However, the exact mechanisms driving these antitumor effects remain largely unclear. In this article, we will review the existing literature on the mechanism of lidocaine as a local anesthetic, its effects on the cancer cells and the tumor microenvironment, involved pathways, and cancer progression. Additionally, we will explore recent reports highlighting its impact on clinical outcomes in cancer patients. Taken together, there remains significant ambiguity surrounding lidocaine's functions and roles in cancer biology, particularly in perioperative setting.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108654"},"PeriodicalIF":13.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological potential of cyclic nucleotide signaling in immunity","authors":"Eirene Marie Q. Ednacot ,&nbsp;Ali Nabhani ,&nbsp;David M. Dinh ,&nbsp;Benjamin R. Morehouse","doi":"10.1016/j.pharmthera.2024.108653","DOIUrl":"10.1016/j.pharmthera.2024.108653","url":null,"abstract":"<div><p>Cyclic nucleotides are important signaling molecules that play many critical physiological roles including controlling cell fate and development, regulation of metabolic processes, and responding to changes in the environment. Cyclic nucleotides are also pivotal regulators in immune signaling, orchestrating intricate processes that maintain homeostasis and defend against pathogenic threats. This review provides a comprehensive examination of the pharmacological potential of cyclic nucleotide signaling pathways within the realm of immunity. Beginning with an overview of the fundamental roles of cAMP and cGMP as ubiquitous second messengers, this review delves into the complexities of their involvement in immune responses. Special attention is given to the challenges associated with modulating these signaling pathways for therapeutic purposes, emphasizing the necessity for achieving cell-type specificity to avert unintended consequences. A major focus of the review is on the recent paradigm-shifting discoveries regarding specialized cyclic nucleotide signals in the innate immune system, notably the cGAS–STING pathway. The significance of cyclic dinucleotides, exemplified by 2′3′-cGAMP, in controlling immune responses against pathogens and cancer, is explored. The evolutionarily conserved nature of cyclic dinucleotides as antiviral agents, spanning across diverse organisms, underscores their potential as targets for innovative immunotherapies. Findings from the last several years have revealed a striking diversity of novel bacterial cyclic nucleotide second messengers which are involved in antiviral responses. Knowledge of the existence and precise identity of these molecules coupled with accurate descriptions of their associated immune defense pathways will be essential to the future development of novel antibacterial therapeutic strategies. The insights presented herein may help researchers navigate the evolving landscape of immunopharmacology as it pertains to cyclic nucleotides and point toward new avenues or lines of thinking about development of therapeutics against the pathways they regulate.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"258 ","pages":"Article 108653"},"PeriodicalIF":13.5,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of natural products and underlying targets for the treatment of aortic aneurysm","authors":"Wenwen Zhao ,&nbsp;Bufan Li,&nbsp;Jinjun Hao,&nbsp;Ruochen Sun,&nbsp;Peng He,&nbsp;Hongyu Lv,&nbsp;Mou He,&nbsp;Jie Shen,&nbsp;Yantao Han","doi":"10.1016/j.pharmthera.2024.108652","DOIUrl":"10.1016/j.pharmthera.2024.108652","url":null,"abstract":"<div><p>Aortic aneurysm is a vascular disease characterized by irreversible vasodilatation that can lead to dissection and rupture of the aortic aneurysm, a life-threatening condition. Thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) are two main types. The typical treatments for aortic aneurysms are open surgery and endovascular aortic repair, which are only indicated for more severe patients. Most patients with aneurysms have an insidious onset and slow progression, and there are no effective drugs to treat this stage. The inability of current animal models to perfectly simulate all the pathophysiological states of human aneurysms may be the key to this issue. Therefore, elucidating the molecular mechanisms of this disease, finding new therapeutic targets, and developing effective drugs to inhibit the development of aneurysms are the main issues of current research. Natural products have been applied for thousands of years to treat cardiovascular disease (CVD) in China and other Asian countries. In recent years, natural products have combined multi-omics, computational biology, and integrated pharmacology to accurately analyze drug components and targets. Therefore, the multi-component and multi-target complexity of natural products have made them a potentially ideal treatment for multifactorial diseases such as aortic aneurysms. Natural products have regained popularity worldwide. This review provides an overview of the known natural products for the treatment of TAA and AAA and searches for potential cardiovascular-targeted natural products that may treat TAA and AAA based on various cellular molecular mechanisms associated with aneurysm development.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108652"},"PeriodicalIF":13.5,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140766622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cisplatin in the era of PARP inhibitors and immunotherapy","authors":"Mingrui Duan ,&nbsp;Shuguang Leng ,&nbsp;Peng Mao","doi":"10.1016/j.pharmthera.2024.108642","DOIUrl":"https://doi.org/10.1016/j.pharmthera.2024.108642","url":null,"abstract":"<div><p>Platinum compounds such as cisplatin, carboplatin and oxaliplatin are widely used in chemotherapy. Cisplatin induces cytotoxic DNA damage that blocks DNA replication and gene transcription, leading to arrest of cell proliferation. Although platinum therapy alone is effective against many tumors, cancer cells can adapt to the treatment and gain resistance. The mechanisms for cisplatin resistance are complex, including low DNA damage formation, high DNA repair capacity, changes in apoptosis signaling pathways, rewired cell metabolisms, and others. Drug resistance compromises the clinical efficacy and calls for new strategies by combining cisplatin with other therapies. Exciting progress in cancer treatment, particularly development of poly (ADP-ribose) polymerase (PARP) inhibitors and immune checkpoint inhibitors, opened a new chapter to combine cisplatin with these new cancer therapies. In this Review, we discuss how platinum synergizes with PARP inhibitors and immunotherapy to bring new hope to cancer patients.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"258 ","pages":"Article 108642"},"PeriodicalIF":13.5,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140554252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultramicronized N-palmitoylethanolamine associated with analgesics: Effects against persistent pain","authors":"Stefania Nobili ,&nbsp;Laura Micheli ,&nbsp;Elena Lucarini,&nbsp;Alessandra Toti,&nbsp;Carla Ghelardini,&nbsp;Lorenzo Di Cesare Mannelli","doi":"10.1016/j.pharmthera.2024.108649","DOIUrl":"10.1016/j.pharmthera.2024.108649","url":null,"abstract":"<div><p>Current epidemiological data estimate that one in five people suffers from chronic pain with considerable impairment of health-related quality of life. The pharmacological treatment is based on first- and second-line analgesic drugs, including COX-2 selective and nonselective nonsteroidal anti-inflammatory drugs, paracetamol, antidepressants, anti-seizure drugs and opioids, that are characterized by important side effects.</p><p><em>N</em>-palmitoylethanolamine (PEA) is a body's own fatty-acid ethanolamide belonging to the family of autacoid local injury antagonist amides. The anti-inflammatory and pain-relieving properties of PEA have been recognized for decades and prompted to depict its role in the endogenous mechanisms of pain control. Together with its relative abundance in food sources, this opened the way to the use of PEA as a pain-relieving nutritional intervention.</p><p>Naïve PEA is a large particle size lipid molecule with low solubility and bioavailability. Reducing particle size is a useful method to increase surface area, thereby improving dissolution rate and bioavailability accordingly. Micron-size formulations of PEA (e.g., ultramicronized and co-(ultra)micronized) have shown higher oral efficacy compared to naïve PEA. In particular, ultramicronized PEA has been shown to efficiently cross the intestinal wall and, more importantly, the blood-brain and blood-spinal cord barrier. Several preclinical and clinical studies have shown the efficacy, safety and tolerability of ultramicronized PEA.</p><p>This narrative review summarizes the available pharmacokinetic/pharmacodynamic data on ultramicronized PEA and focuses to its contribution to pain control, in particular as ‘add-on’ nutritional intervention. Data showing the ability of ultramicronized PEA to limit opioid side effects, including the development of tolerance, have also been reviewed.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"258 ","pages":"Article 108649"},"PeriodicalIF":13.5,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016372582400069X/pdfft?md5=5ac0e4b197e65d33a3b7c1edb7627f9f&pid=1-s2.0-S016372582400069X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140766459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}