المؤلفون: Liu, Guozheng, Zhang, Yanwen, Huang, Yong

المصدر: European Journal of Cancer Care; 4/8/2024, Vol. 2024, p1-12, 12p

مصطلحات موضوعية: BREAST cancer prognosis, THERAPEUTIC use of antineoplastic agents, BREAST tumor treatment, THERAPEUTIC use of monoclonal antibodies, ANTIANDROGENS, MITOGEN-activated protein kinases, CANCER relapse, T cells, TRASTUZUMAB, BREAST tumors, IMMUNOTHERAPY, PROGRAMMED death-ligand 1, APOPTOSIS, ENZYME inhibitors, AGE distribution, TUMOR markers, METASTASIS, ADJUVANT chemotherapy, IMMUNE checkpoint inhibitors, COMBINED modality therapy, PROGRAMMED cell death 1 receptors, MTOR inhibitors, PROGRESSION-free survival, INDIVIDUALIZED medicine, PHENOTYPES, OVERALL survival

مستخلص: Women around the world are most frequently afflicted with breast cancer, and it is one of the most frequent causes of cancer death in females. Breast cancer is usually classified according to biomarker status, triple‐negative breast cancer (TNBC) represents a distinct subtype characterized by immunohistochemical findings that denote negativity for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (Her-2) on cancer tissue. It is more common in younger women than in other subtypes. As an invasive breast cancer subtype with a unique drug-resistant phenotype and metastatic burden, it has limited treatment options, and patients have a poor prognosis with high rates of local, distant recurrence and mortality, and there is still a lack of standardized treatment protocols for TNBC. In this review, we delve into the current treatment strategies for TNBC and explore the potential for new approaches and targets in the future. This trial is registered with NCT03997123. [ABSTRACT FROM AUTHOR]

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المؤلفون: Yu, Ji Eun, Kim, Yuri, Hong, Da Eun, Lee, Dong Won, Chang, Ju Young, Yoo, Seung Sik, Kim, Min Ji, Son, Dong Ju, Yun, Jaesuk, Han, Sang-Bae, Hong, Jin Tae

المصدر: Journal of Oncology; 12/23/2022, p1-13, 13p

مصطلحات موضوعية: FLOW cytometry, STATISTICS, WASPS, CELL culture, AUTOPHAGY, WESTERN immunoblotting, IMMUNOHISTOCHEMISTRY, LUNG tumors, APOPTOSIS, MTOR inhibitors, PAIRED comparisons (Mathematics), CELLULAR signal transduction, CELL survival, ARTHROPOD venom, BEES, DESCRIPTIVE statistics, CELL lines, POLYMERASE chain reaction, HYDROXYCHLOROQUINE, DATA analysis, DATA analysis software, PHARMACODYNAMICS

مستخلص: In oriental medicine, bee venom has long been used as a therapeutic agent against inflammatory diseases. Several studies have reported that isolated and purified bee venom components are effective in treating dementia, arthritis, inflammation, bacterial infections, and cancer. In previous studies, we reported that bee venom inhibits cell growth and induces apoptotic cell death in lung cancer cells. In the present study, we assessed whether bee venom affects autophagy and thereby induces apoptosis. Bee venom treatment increased the levels of autophagy-related proteins (Atg5, Beclin-1, and LC3-II) and the accumulation of LC3 puncta. We found that bee venom could induce autophagy by inhibiting the mTOR signaling pathway. In addition, we found that hydroxychloroquine (HCQ)- or si-ATG5-induced autophagy inhibition further demoted bee venom-induced apoptosis. Bee venom-induced autophagy promotes apoptosis in lung cancer cells and may become a new approach to cancer treatment. [ABSTRACT FROM AUTHOR]

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المؤلفون: Hu, Huiling, Luo, Zhijun, Liu, Xiuli, Huang, Lisi, Lu, Xiaoxia, Ding, Rui, Duan, Chaohui, He, Yuqing

المصدر: International Journal of Endocrinology; 12/10/2022, Vol. 2022, p1-11, 11p

مصطلحات موضوعية: IN vitro studies, HOMEOSTASIS, ENDOPLASMIC reticulum, NUCLEAR proteins, NUCLEOSIDES, WESTERN immunoblotting, MTOR inhibitors, APOPTOSIS, ANTIOXIDANTS, SIGNAL peptides, OXIDATIVE stress, GENE expression, CELLULAR signal transduction, CELL survival, DESCRIPTIVE statistics, CELL lines, POLYMERASE chain reaction, DATA analysis software, ANTIBIOTICS, HEPATOCELLULAR carcinoma, PHARMACODYNAMICS

مستخلص: Sestrin2 is a highly conserved stress-inducible protein, acting as a crucial part in regulating homeostasis in response to various stress conditions in the cell. However, the role of Sestrin2 in regulating cell apoptosis related to endoplasmic reticulum (ER) has not been fully investigated. Our study presented here aims to reveal the effect of Sestrin2 in tunicamycin (TM)-induced cell apoptosis related to ER stress and its underlying molecular mechanisms. The results demonstrated that Sestrin2 expression was significantly upregulated correlated with ER stress responses in TM treated HepG2 cells. Sestrin2 overexpression obviously alleviated ER stress with the determination of ER stress-related proteins expression. In addition, Sestrin2 overexpression inhibited cell apoptosis with the examination of apoptosis-related proteins and TUNEL assay. However, Sestrin2 knockdown further promoted the ER stress-mediated cell apoptosis. The further mechanistic study revealed that Sestrin2 overexpression inhibited TM-induced mTOR pathway activation. Taken together, our current study indicated that Sestrin2 overexpression ameliorates ER stress-induced apoptosis via inhibiting mTOR pathway in HepG2 cells. [ABSTRACT FROM AUTHOR]

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المؤلفون: Guan, Shuyuan, Sun, Lingbin, Wang, Xihua, Huang, Xirui, Luo, Tao

المصدر: Evidence-based Complementary & Alternative Medicine (eCAM); 11/23/2022, p1-8, 8p, 1 Diagram, 5 Graphs

مصطلحات موضوعية: LIPOPOLYSACCHARIDES, RODENTS, CYTOKINES, INTERLEUKINS, CYCLOOXYGENASE 2, IN vitro studies, FLAVONOIDS, NITRIC-oxide synthases, ANTI-inflammatory agents, ANIMAL experimentation, NONSTEROIDAL anti-inflammatory agents, METABOLISM, METABOLIC reprogramming, PHOSPHATASES, MTOR inhibitors, NEUROINFLAMMATION, GENE expression, DNA-binding proteins, TUMOR necrosis factors, TRANSFERASES, NEUROGLIA, PLANT extracts, CELL lines, NITRIC oxide, MITOGEN-activated protein kinases, PHOSPHORYLATION, PHARMACODYNAMICS, CHEMICAL inhibitors

مستخلص: Isoschaftoside is a C-glycosyl flavonoid extracted from the root exudates of Desmodium uncinatum and Abrus cantoniensis. Previous studies suggested that C-glycosyl flavonoid has neuroprotective effects with the property of reducing oxidative stress and inflammatory markers. Microglia are key cellular mediators of neuroinflammation in the central nervous system. The aim of this study was to investigate the effect of isoschaftoside on lipopolysaccharide-induced activation of BV-2 microglial cells. The BV-2 cells were exposed to 10 ng/ml lipopolysaccharide and isoschaftoside (0–1000 μM). Isoschaftoside effectively inhibited lipopolysaccharide-induced nitric oxide production and proinflammatory cytokines including iNOS, TNF-α, IL-1β, and COX2 expression. Isoschaftoside also significantly reduced lipopolysaccharide-induced HIF-1α, HK2, and PFKFB3 protein expression. Induction of HIF-1α accumulation by CoCl2 was inhibited by isoschaftoside, while the HIF-1α specific inhibitor Kc7f2 mitigated the metabolic reprogramming and anti-inflammatory effect of isoschaftoside. Furthermore, isoschaftoside attenuated lipopolysaccharide-induced phosphorylation of ERK1/2 and mTOR. These results suggest that isoschaftoside can suppress inflammatory responses in lipopolysaccharide-activated microglia, and the mechanism was partly due to inhibition of the HIF-1α-mediated metabolic reprogramming pathway. [ABSTRACT FROM AUTHOR]

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المؤلفون: Zhao, Weidong, Zhao, Xiaohan, Xu, Menglin, Cheng, Zhengwu, Zhang, Zhengxiang

المصدر: Journal of Oncology; 11/8/2022, p1-12, 12p

مصطلحات موضوعية: STOMACH tumors, BIOLOGICAL models, IN vitro studies, NONPARAMETRIC statistics, IN vivo studies, XENOGRAFTS, ANALYSIS of variance, ANIMAL experimentation, WESTERN immunoblotting, MTOR inhibitors, METASTASIS, LYMPH nodes, CELL motility, CELLULAR signal transduction, T-test (Statistics), GENE expression, CELL cycle, CELL proliferation, DESCRIPTIVE statistics, CHI-squared test, KAPLAN-Meier estimator, SURVIVAL analysis (Biometry), TUMOR markers, CELL lines, POLYMERASE chain reaction, DATA analysis software, MICE, PHOSPHORYLATION

مستخلص: Objective. To explore the functional and molecular mechanism of long noncoding RNA LINC01279 in gastric cancer (GC). Methods. The LINC01279 expression in GC and tissues of para-carcinoma was detected by qPCR (real-time fluorescent quantitative PCR), and the association between the LINC01279 expression and clinicopathological features of patients with GC was investigated. The colony formation, CCK-8, transwell assays, and cell cycle detection kit were used for detection of the effect of LINC01279 on GC cell proliferation, cell cycle, colony formation, and invasion. The effect of LINC01279 on PI3K/AKT/mTOR in the GC signaling pathway was identified by the Western blotting technique. The effect of LINC01279 on GC cell proliferation in vivo was evaluated by subcutaneous xenograft tumors in the nude mice. Results. The results of qPCR displayed the expression of LINC01279 was higher in tissues of GC patients. Furthermore, the tumor size, TNM stage, and metastasis of lymph nodes were also closely related to LINC01279 expression. The experiments on cell function showed that the LINC01279 knockdown significantly inhibited the colony formation, invasion, and proliferation of GC cells and induced the cell cycle arrest in G0 and G1 phases. The Western blotting technique also showed that LINC01279 knockdown significantly inhibited the phosphorylation of PI3K, Akt, and mTOR in GC cells. Furthermore, in vivo experiments displayed that the LINC01279 knockdown significantly inhibited the GC growth. Conclusion. Knockdown of LINC01279 plays a significant role in inhibiting the PI3K/AKT/mTOR signaling pathway which affects the GC invasion and proliferation. The LINC01279 expression can be utilized as a biomarker for the prediction of the GC prognosis. [ABSTRACT FROM AUTHOR]

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المؤلفون: Hartinger, Jan Miroslav, Ryšánek, Pavel, Slanař, Ondřej, Šíma, Martin

المصدر: Journal of Clinical Pharmacy & Therapeutics; Sep2022, Vol. 47 Issue 9, p1362-1367, 6p

مصطلحات موضوعية: ABSORPTION, RAPAMYCIN, PATIENTS, MTOR inhibitors, PHARMACEUTICAL arithmetic, EVEROLIMUS, DRUG monitoring, TRANSPLANTATION of organs, tissues, etc.

مستخلص: What Is Known and Objectives: mTOR inhibitors possess narrow therapeutic range and substantial pharmacokinetic variability and the consequences from suboptimal dosing are serious. The aim of this review is to summarize the current knowledge about the factors influencing mTOR inhibitors pharmacokinetics and the possibility of using these relationships in order to improve its therapy individualization in solid organ transplanted patients. Methods: Literature search from Pubmed and Web of Science databases were performed using Boolean search operators in order to identify relevant studies. Results and Discussion: A total of 701 reports were identified from the initial literature search. Out of which 40 studies dealt with relationships between various factors and pharmacokinetics of mTOR inhibitors and with relevance of these associations for dosage optimization. What Is New and Conclusion: The overview of the current covariates for pharmacokinetic variability of mTOR inhibitors has been provided on the level of absorption, distribution and elimination, and consequences of these relationships for dosing optimization has been summarized. [ABSTRACT FROM AUTHOR]

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المؤلفون: Song, Tao, Zhang, Huazhou

المصدر: Breast Journal; 8/28/2022, Vol. 2022, p1-13, 13p

مصطلحات موضوعية: XENOGRAFTS, CELL culture, RNA-binding proteins, WESTERN immunoblotting, METASTASIS, MTOR inhibitors, APOPTOSIS, HEALTH outcome assessment, CELLULAR signal transduction, CELL survival, CELL motility, CISPLATIN, CELL proliferation, DESCRIPTIVE statistics, POLYMERASE chain reaction, CELL lines, BREAST tumors, DRUG resistance in cancer cells, PHARMACODYNAMICS

مستخلص: Background. Breast cancer (BC) is the most prevalent malignancy in women. This study is aimed to explore the role and regulatory mechanism of RNA-binding motif protein 8A (RBM8A) in BC. Methods. We detected the expression of RBM8A in BC tissues and cell lines (MCF-7, MDA-MB-231, and MDA-MB-436), and explored the correlation of RBM8A expression with clinicopathological features in patients. The function of RBM8A deficiency in MCF-7 and MDA-MB-231 cells was determined using MTT, wound healing, and transwell assay. The effect of RBM8A suppression on the cisplatin (DDP) resistance in MCF-7 and MDA-MB-231 cells was also evaluated. Besides, western blotting was used to examine AKT/mTOR pathway-related proteins. The mouse model was constructed to confirm the effect of RBM8A on tumor growth. Results. The expression of RBM8A was elevated in BC tissues and cell lines. RBM8A silencing restrained the malignant behaviors of MCF-7 and MDA-MB-231 cells, including viability, migration, and invasion, while promoting apoptosis. Silencing of RBM8A overcame resistance to DDP in MCF-7 and MDA-MB-231 cells. Furthermore, RBM8A suppression restrained the activation of the AKT/mTOR pathway in both MCF-7 and MDA-MB-231 cells. Feedback experiments revealed that SC79 treatment reversed the reduction effects of RBM8A knockdown on viability, DDP resistance, migration, and invasion of MDA-MB-231 cells. Moreover, the silencing of RBM8A inhibited the growth of tumor xenograft in vivo. Conclusions. RBM8A knockdown may reduce DDP resistance in BC to repress the development of BC via the AKT/mTOR pathway, suggesting that RBM8A may serve as a new therapeutic target in BC. [ABSTRACT FROM AUTHOR]

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المؤلفون: Gao, Huijie, Ren, Yan, Liu, Chao

المصدر: Evidence-based Complementary & Alternative Medicine (eCAM); 8/8/2022, p1-7, 7p, 2 Diagrams, 1 Chart, 3 Graphs

مصطلحات موضوعية: QUINONE, INTERLEUKINS, CYTOKINES, INFLAMMATION, PHOSPHOTRANSFERASES, ANIMAL experimentation, WESTERN immunoblotting, INTRAPERITONEAL injections, MTOR inhibitors, OXIDATIVE stress, SEPSIS, TUMOR necrosis factors, ENZYME-linked immunosorbent assay, POLYMERASE chain reaction, MICE

مستخلص: Background. This study was designed to assess the impact of aloe-emodin (AE) on oxidative stress and inflammation in a murine model of LPS-induced sepsis. In addition, the mechanistic basis for anti-inflammatory and antioxidant activity was assessed. Methods. Male ICR mice received an intraperitoneal injection of LPS (10 mg/kg), and the preventive properties of AE (80 or 150 mg/kg) on these mice were assessed by monitoring spleen index, and levels of inflammatory and oxidative stress-related factors. Peripheral blood TNF-α and IL-6 levels were assessed via ELISA kits, while changes in hepatic SOD and GSH-Px levels were assessed using appropriate biochemical kits. Splenic PI3K, AKT, and mTOR levels were assessed via qPCR and western blotting. Results. Relative to animals in the LPS model group, those in the AE treatment groups exhibited reduced spleen index, decreased inflammatory cytokine levels, and improved SOD and GSH-Px activity in liver tissues. Splenic PI3K, Akt, and mTOR levels were also reduced in response to AE treatment. Conclusions. These findings indicated that AE can alleviate sepsis-related tissue damage, inflammation, and oxidative stress, at least in part by suppressing the PI3K/Akt/mTOR signaling pathway. These results offer a clinical basis for the use of AE to treat sepsis and associated diseases. [ABSTRACT FROM AUTHOR]

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المؤلفون: Huang, Liaoyuan, Chen, Jianming, Wu, Danhai, Wang, Kan, Lou, Weigang, Wu, Jianmin

المصدر: BioMed Research International; 7/23/2022, p1-11, 11p

مصطلحات موضوعية: THERAPEUTIC use of alkaloids, INTERLEUKINS, SPINE diseases, STAINS & staining (Microscopy), ALKALOIDS, ANIMAL experimentation, AUTOPHAGY, INTERVERTEBRAL disk, MTOR inhibitors, SIGNAL peptides, APOPTOSIS, HEALTH outcome assessment, CELLULAR signal transduction, CELL nuclei, RATS, IMMUNOBLOTTING, CELL proliferation, FLUORESCENT antibody technique, DESCRIPTIVE statistics, PHARMACODYNAMICS

مستخلص: Intervertebral disc degeneration (IDD) is a chronic progressive condition mainly caused by excessive inflammatory cytokines. Berberine (BBR) exerts anti-inflammatory effect on diseases and protective effect against IDD. However, the mechanism is not uncertain. This study is aimed at investigating the molecular mechanism of BBR on IDD. Nucleus pulposus (NP) cells were treated with BBR at different concentrations. The IDD rat model was established by acupuncture. The effect of BBR on interleukin- (IL-) 1β-induced cell proliferation was measured by CCK-8 assay and BrdU staining. The role of BBR in IL-1β-induced apoptosis, autophagy repression, and extracellular matrix (ECM) degradation was measured by Annexin/PI staining, immunofluorescence, and immunoblot. The effect of BBR on IDD was investigated in rat. Our findings showed that BBR restored cell growth and attenuated apoptosis in IL-1β-induced NP cells. BBR also prevented the IL-1β-induced ECM degradation through regulating ECM-related enzymes and factors. Additionally, BBR significantly activated autophagy repressed by IL-1β. Autophagy stimulated by BBR was diminished by the inhibition of the AMPK/mTOR/Ulk1 signaling pathway. In vivo study also showed BBR attenuated intervertebral disc degeneration. BBR could attenuate NP cells apoptosis and ECM degradation induced by IL-1β through autophagy by the AMPK/mTOR/Ulk1 pathway. This study suggests BBR might function as an AMPK activator to alleviate IDD progression. [ABSTRACT FROM AUTHOR]

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المؤلفون: Wang, Zizong, Yang, Bin, Zhang, Jin, Chu, Xiangyang

المصدر: BioMed Research International; 7/8/2022, p1-16, 16p

مصطلحات موضوعية: RNA metabolism, LUNG cancer, DISEASE progression, COMPETITIVE endogenous RNA, EXPERIMENTAL design, CELL migration, WESTERN immunoblotting, MICROBIOLOGICAL assay, MTOR inhibitors, CELLULAR signal transduction, BIOINFORMATICS, GENE expression, DESCRIPTIVE statistics, POLYMERASE chain reaction

مستخلص: Objectives. This study focused on the biological functions and mechanisms of action of LINC01554 in nonsmall cell lung cancer (NSCLC). Methods. The expression and prognostic values of LINC01554 in NSCLC were evaluated using The Cancer Genome Atlas datasets. MTT, colony formation, wound healing, transwell, and in vivo assays were performed to investigate the role of LINC01554 in NSCLC. The related protein expression levels were measured via western blotting. Bioinformatic analysis was conducted to predict targeted genes. The relationship between LINC01554, microRNA- (miR-) 1267, miR-1267, and inhibitor of growth family member 3 (ING3) was analysed via a dual-luciferase reporter assay. Results. LINC01554 expression was downregulated in NSCLC and associated with NSCLC prognosis. LINC01554 overexpression suppressed NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Bioinformatic and dual-luciferase reporter assays demonstrated that LINC01554 expression directly targeted miR-1267 expression, which in turn directly acted on ING3. An miR-1267 mimic significantly reduced ING3 expression, whereas an miR-1267 inhibitor observably elevated its expression. LINC01554 overexpression increased ING3 expression, whereas this effect was counteracted by the miR-1267 mimic. LINC01554 overexpression also significantly suppressed the expression of phosphorylated protein kinase B (Akt) and phosphorylated mammalian target of rapamycin (mTOR) expression; this effect was abrogated by the miR-1267 mimic. Mechanistically, LINC01554 overexpression repressed the growth, migration, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells through the regulation of the miR-1267/ING3 axis via regulation of the Akt/mTOR signalling pathway. Conclusions. We provide the first evidence of the involvement of the LINC01554/miR-1267 axis in NSCLC proliferation and metastasis through the ING3Akt/mTOR pathway. Thus, LINC01554 may serve as a novel therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

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