Crucial Role of Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications DOI Creative Commons
A I Ferreira, Flávia Pereira, Celso A. Reis

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(14), P. 2183 - 2183

Published: July 13, 2022

KRAS, one of the RAS protein family members, plays an important role in autophagy and apoptosis, through regulation several downstream effectors. In cancer cells, KRAS mutations confer constitutive activation this oncogene, stimulating cell proliferation, inducing autophagy, suppressing altering metabolism, changing motility invasion modulating tumor microenvironment. order to inhibit these oncogenic were reported upregulate anti-apoptotic proteins, including Bcl-xL survivin, downregulate proteins related apoptosis induction, thymine-DNA glycosylase (TDG) necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). addition, are known induce promote survival progression MAPK PI3K regulation. Thus, resistance anti-cancer drug treatment and, consequently, result poor prognosis. Several therapies have been developed overcome KRAS-induced death signaling pathways blockade, especially by combining inhibitors, which demonstrated promising results. Understanding involvement regulation, might bring new avenues discovery therapeutic approaches for CRCs harboring mutations.

Language: Английский

Circular RNA vaccines against SARS-CoV-2 and emerging variants DOI Creative Commons
Liang Qu, Zongyi Yi, Yong Shen

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(10), P. 1728 - 1744.e16

Published: April 1, 2022

As the emerging variants of SARS-CoV-2 continue to drive worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report circular RNA (circRNA) vaccine elicited potent neutralizing antibodies T cell responses by expressing trimeric RBD spike protein, providing robust protection against in both mice rhesus macaques. Notably, circRNA enabled higher durable antigen production than 1mΨ-modified mRNA proportion distinct Th1-skewed immune responses. Importantly, found circRNARBD-Omicron induced Omicron but not Delta variant. In contrast, circRNARBD-Delta protected or functioned as booster after two doses either native- Delta-specific vaccination, making it favorable choice current concern (VOCs) SARS-CoV-2.

Language: Английский

Citations

410
Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer DOI Creative Commons
Jing‐Jing Yang, Yulu Zhou,

Shuduo Xie

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: June 23, 2021

Ferroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation lipid peroxidation and involved in various pathophysiological conditions, including cancer. Targeting ferroptosis considered to be novel anti-cancer strategy. The identification FDA-approved drugs as inducers proposed new promising approach for cancer treatment. Despite growing body evidence indicating potential efficacy anti-diabetic metformin an agent, exact mechanism underlying this has not yet been fully elucidated.The UFMylation SLC7A11 detected immunoprecipitation expression UFM1 tumor tissues was immunohistochemical staining. level determined free iron, total/lipid Ros GSH cells morphological changes mitochondria are observed transmission electron microscope. vivo verified situ implantation model nude mice.Metformin induces AMPK-independent manner suppress growth. Mechanistically, we demonstrate that increases intracellular Fe2+ ROS levels. Specifically, reduces protein stability SLC7A11, which critical regulator, inhibiting its process. Furthermore, combined with sulfasalazine, system xc- inhibitor, can work synergistic induce inhibit proliferation breast cells.This study first ability may effect. In addition, identified substrate found targeting UFM1/SLC7A11 pathway could treatment

Language: Английский

Citations

261
Chitosan nanoparticles as a promising tool in nanomedicine with particular emphasis on oncological treatment DOI Creative Commons
Javad Sharifi‐Rad, Cristina Quispe, Monica Butnariu

et al.

Cancer Cell International, Journal Year: 2021, Volume and Issue: 21(1)

Published: June 24, 2021

Abstract The study describes the current state of knowledge on nanotechnology and its utilization in medicine. focus this manuscript was properties, usage safety, potentially valuable applications chitosan-based nanomaterials. Chitosan nanoparticles have high importance nanomedicine, biomedical engineering, discovery development new drugs. reviewed studies regarding use for creating release systems with improved bioavailability, increased specificity sensitivity, reduced pharmacological toxicity Nowadays, effective cancer treatment is a global problem, recent advances nanomedicine are great importance. Special attention put application chitosan developing system anticancer drug delivery. Pre-clinical clinical support nanomedicine. This overviews last progresses utilization, stability, bioavailability nanoencapsulation their safety.

Language: Английский

Citations

227
Tumor biomarkers for diagnosis, prognosis and targeted therapy DOI Creative Commons
Yue Zhou, Lei Tao, Jiahao Qiu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 20, 2024

Abstract Tumor biomarkers, the substances which are produced by tumors or body’s responses to during tumorigenesis and progression, have been demonstrated possess critical encouraging value in screening early diagnosis, prognosis prediction, recurrence detection, therapeutic efficacy monitoring of cancers. Over past decades, continuous progress has made exploring discovering novel, sensitive, specific, accurate tumor significantly promoted personalized medicine improved outcomes cancer patients, especially advances molecular biology technologies developed for detection biomarkers. Herein, we summarize discovery development including history conventional innovative used biomarker classification biomarkers based on tissue origins, application clinical management. In particular, highlight recent advancements biomarker-based anticancer-targeted therapies emerging as breakthroughs promising strategies. We also discuss limitations challenges that need be addressed provide insights perspectives turn into opportunities this field. Collectively, multiple emphasized review may guidance precision medicine, broaden horizons future research directions, expedite patients according their rather than organs origin.

Language: Английский

Citations

160
Reprogramming of glutamine metabolism and its impact on immune response in the tumor microenvironment DOI Creative Commons
Guofeng Ma, Zhilei Zhang, Peng Li

et al.

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: July 27, 2022

Abstract Metabolic reprogramming and immune escape play a major role in tumorigenesis. Increasing number of studies have shown that glutamine metabolism is putative determinant the anti-tumor response tumor microenvironment (TME). Usually, predatory uptake by cells TME results limited utilization affects response. The cell-programmed partitioning also However, tumors modulates regulating PD-L1 expression. Likewise, their function. Additionally, different types inhibitors extensively regulate while suppressing cell proliferation. Herein, we discuss how metabolic regulates responses, as well functional changes context targeting metabolism, which can better explain potential combination with immunotherapy for cancer.

Language: Английский

Citations

118
Metabolism and Colorectal Cancer DOI Creative Commons
Joseph C. Sedlak, Ömer Yılmaz, Jatin Roper

et al.

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2022, Volume and Issue: 18(1), P. 467 - 492

Published: Nov. 2, 2022

Reprogrammed metabolism is a hallmark of colorectal cancer (CRC). CRC cells are geared toward rapid proliferation, requiring nutrients and the removal cellular waste in nutrient-poor environments. Intestinal stem (ISCs), primary cell origin for CRCs, must adapt their along adenoma-carcinoma sequence to unique features complex microenvironment that include interactions with intestinal epithelial cells, immune stromal commensal microbes, dietary components. Emerging evidence implicates modifiable risk factors related environment, such as diet, important pathogenesis. Here, we focus on describing ISCs, diets influence initiation, genetics metabolism, tumor microenvironment. The mechanistic links between environmental factors, metabolic adaptations, enhancing or supporting tumorigenesis becoming better understood. Thus, greater knowledge holds promise improved prevention treatment.

Language: Английский

Citations

100
Induction and application of ferroptosis in cancer therapy DOI Creative Commons
Qing Nie, Yue Hu, Xiao Yu

et al.

Cancer Cell International, Journal Year: 2022, Volume and Issue: 22(1)

Published: Jan. 7, 2022

At present, more than one cell death pathways have been found, of which is ferroptosis. Ferroptosis was discovered in 2012 and described as an iron-dependent lipid peroxidation-driven regulated pathway. In the past few years, ferroptosis has shown to induce tumor death, providing new ideas for treatment. this article, we summarize latest advances ferroptosis-induced therapy at intersection biology, molecular redox materials chemistry. First, state characteristics cells, then introduce key mechanism ferroptosis, describes relationship between oxidative stress signaling pathways. Finally, focused on several types inducers by scholars, application systemic chemotherapy, radiotherapy, immunotherapy nanomedicine, hope that can exert its potential treatment tumors.

Language: Английский

Citations

92
The Role of NQO1 in Ovarian Cancer DOI Open Access
Giovanni Tossetta, Sonia Fantone, Gaia Goteri

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 7839 - 7839

Published: April 25, 2023

Ovarian cancer is one of the most dangerous gynecologic malignancies showing a high fatality rate because late diagnosis and relapse occurrence due to chemoresistance onset. Several researchers reported that oxidative stress plays key role in ovarian occurrence, growth development. The NAD(P)H:quinone oxidoreductase 1 (NQO1) an antioxidant enzyme that, using NADH or NADPH as substrates reduce quinones hydroquinones, avoids formation highly reactive semiquinones, then protecting cells against stress. In this review, we report evidence from literature describing effect NQO1 on onset progression.

Language: Английский

Citations

62
Targeting GPX4 in human cancer: Implications of ferroptosis induction for tackling cancer resilience DOI
Jaewang Lee, Jong‐Lyel Roh

Cancer Letters, Journal Year: 2023, Volume and Issue: 559, P. 216119 - 216119

Published: March 7, 2023

Language: Английский

Citations

61
Mechanisms of and Potential Medications for Oxidative Stress in Ovarian Granulosa Cells: A Review DOI Open Access

Siheng Liu,

Yunbing Jia,

Shirui Meng

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9205 - 9205

Published: May 24, 2023

Granulosa cells are essential for follicle initiation and development, their abnormal function or apoptosis is a crucial factor leading to follicular atresia. A state of oxidative stress occurs when the balance between production reactive oxygen species regulation antioxidant system disturbed. Oxidative one most important causes granulosa cells. in female reproductive diseases, such as polycystic ovary syndrome premature ovarian failure. In recent years, studies have confirmed that mechanism closely linked PI3K-AKT signaling pathway, MAPK FOXO axis, Nrf2 NF-κB mitophagy. It has been found drugs sulforaphane, Periplaneta americana peptide, resveratrol can mitigate functional damage caused by on This paper reviews some mechanisms involved describes underlying pharmacological treatment

Language: Английский

Citations

53