Photodynamic therapy (PDT) is a photochemistry-involved treatment that utilizes light-activatable photosensitizers (PSs) to generate cytotoxic reactive oxygen species (ROS), for example, singlet oxygen (SO), under a specific wavelength of light, thus causing cell apoptosis and tissue damage. [1] PS is an indispensable tool for PDT, among them, porphyrin and its derivatives are the most commonly used PSs, but their bioavailability is limited due to tumor nonspecificity and rapid cellular elimination. [2] With the development of nanotechnology, a series of porphyrin-based nanometal-organic frameworks (NMOFs), as a class of porous crystalline materials, have been developed as PSs for its advantages of high surface area and facilely tunable pore sizes. [3] Especially, Zr (IV)-based porphyrinic NMOFs (PCN-224) could not only being provided as nanocarriers to load drugs, [4] but also itself is a good kind of PSs with deep penetration, and could be further encapsulated by delivery systems for targeted antitumor therapy. [5,6] Recently, the combination of multifunctional treatments involve chemodynamic therapy, chemotherapy, gene transfection, photothermal therapy and gas therapy with PDT has immerged as promising strategies, which could remarkably elevate antitumor efficacy of PDT. [7][8][9] Gas therapy, which applies gaseous signaling molecules, such as nitric oxide, hydrogen sulfide, and carbon monoxide (CO), to treat cancer, has been proposed as a "green" treatment for its negligible side effects. [10][11][12] Among the endogenous gaseous molecules, CO has encompassed a broad effect on apoptosis, [13] and it plays a role in inflammation and wound healing when at low dosage, [14][15][16][17] whereas, it will induce pro-apoptosis in cancer cells via preventing mitochondrial respiration and affecting cellular protein synthesis when at a high dosage. [18,19] Thus, it could be a feasible strategy for antitumor therapy as long as only targeted delivery and controlled release of high amounts of CO in tumor tissues rather than directly inhaling high dosage of CO leading to severe systemic toxicity via reducing The apoptosis-resistant mechanism of photodynamic therapy (PDT) usually results in limited therapeutic efficacy. The development of new strategies for sensitizing targeted ferroptosis that bypass apoptosis resistance is of great significance to improve the antitumor efficacy of PDT. In this study, a novel amphiphilic copolymer whose main chain contains reactive oxygen species (ROS)-responsive groups and the end of side chains contains triphenylphosphine is synthesized, to encapsulate porphyrinic metal-organic framework PCN-224 via self-assembly which are hydrothermally synthesized by co ordination of zirconium (IV) with tetra-kis(4-caboxyphenyl) porphyrin, and loaded carbon monoxide releasing molecule 401 (CORM-401) by their hollow structures (PCN-CORM), and finally, surface-coated with hyaluronic acid. The nanosystem can sequentially localize to mitochondria which is an important target to induce apoptosis and ferropt...
Lung adenocarcinoma is a malignant and fatal respiratory disease. However, due to its complex pathogenesis and poorly effective therapeutic options, accurate early diagnosis and prognosis remain elusive. Now, there is increasing evidence that tumor stem cells are involved in tumorigenesis, metastasis, relapse, resistance to chemotherapy and radiotherapy and are one of the reasons why tumors cannot be cured. The mRNA expression based-stemness index (mRNAsi) is a parameter obtained by Malta and his colleagues applying innovative one-class logistic regression machine learning algorithm (OCLR) on mRNA expression in normal stem cells and their progeny. It is a valid evaluation parameter and is currently employed to evaluate the degree of differentiation of a certain tumor. In this study, we first used WGCNA and the software Cytoscape to obtain key modules and hub genes. We then applied LASSO regression analysis to calculate the genes in the key module to obtain a six-gene risk model. Moreover, the accuracy of this model was validated. Finally, we took the intersection of hub genes and risk genes and validated CENPA as both a tumor stemness regulator and a tumor prognostic factor in lung cancer.
Gastric cancer remains a malignant disease of the digestive tract with high mortality and morbidity worldwide. However, due to its complex pathological mechanisms and lack of effective clinical therapies, the survival rate of patients after receiving treatment is not satisfactory. An increasing number of studies have focused on cancer stem cells and their regulatory properties. In this study, we first constructed a coexpression network based on the WGCNA algorithm to identify modules with different degrees of association with tumor stemness indices. After selecting the most positively correlated modules of the stemness index, we performed a consensus clustering analysis on gastric cancer samples and constructed the co-expression network again. We then selected the modules of interest and applied univariate COX regression analysis to the genes in this module for preliminary screening. The results of the screening were then used in LASSO regression analysis to construct a risk prognostic model and subsequently a sixteen-gene model was obtained. Finally, after verifying the accuracy of the module and screening for risk genes, we identified MAGE-A3 as the final study subject. We then performed in vivo and in vitro experiments to verify its effect on tumor stemness and tumour proliferation. Our data supports that MAGE-A3 is a tumor stemness regulator and a potent prognostic biomarker which can help the prediction and treatment of gastric cancer patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.