The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2652 - 2652

Published: Jan. 31, 2023

Hepatocellular carcinoma (HCC) is one of the leading causes cancer-related deaths in world. Metabolic reprogramming considered a new hallmark cancer, but it remains unclearly described HCC. The dysregulation PI3K/AKT/mTOR signaling pathway common HCC and is, therefore, topic further research concern developing novel target for liver cancer therapy. In this review, we illustrate mechanisms by which network accountable regulating cellular metabolism, including glucose lipid amino acid pyrimidine oxidative summarize ongoing clinical trials based on inhibition

Language: Английский

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The molecular feature of macrophages in tumor immune microenvironment of glioma patients

Computational and Structural Biotechnology Journal, Journal Year: 2021, Volume and Issue: 19, P. 4603 - 4618

Published: Jan. 1, 2021

Gliomas are one of the most common types primary tumors in central nervous system. Previous studies have found that macrophages actively participate tumor growth.Weighted gene co-expression network analysis was used to identify meaningful macrophage-related genes for clustering. Pamr, SVM, and neural were applied validating clustering results. Somatic mutation methylation defining features identified clusters. Differentially expressed (DEGs) between stratified groups after performing elastic regression principal component analyses construction MScores. The expression macrophage-specific evaluated microenvironment based on single cell sequencing analysis. A total 2365 samples from 15 glioma datasets 5842 pan-cancer external validation MScore.Macrophages be negatively associated with survival patients. Twenty-six DEGs obtained by PCA highly at single-cell level. prognostic value MScores validated active proinflammatory metabolic profile infiltrating response immunotherapies this signature. managed stratify patient probabilities datasets, which predicted worse outcome. Sequencing data immunohistochemistry Xiangya cohort confirmed model demonstrated high accuracy rate.Our findings strongly support a modulatory role macrophages, especially M2 progression warrants further experimental studies.

Language: Английский

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Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: April 27, 2022

Abstract Targeting nucleotide metabolism can not only inhibit tumor initiation and progression but also exert serious side effects. With in-depth studies of metabolism, our understanding in tumors has revealed their non-proliferative effects on immune escape, indicating the potential effectiveness antimetabolites for enhancing immunotherapy. A growing body evidence now supports concept that targeting increase antitumor response by (1) activating host systems via maintaining concentrations several important metabolites, such as adenosine ATP, (2) promoting immunogenicity caused increased mutability genomic instability disrupting purine pyrimidine pool, (3) releasing nucleoside analogs microbes to regulate immunity. Therapeutic approaches combined with immunotherapy have achieved exciting success preclinical animal models. Here, we review how dysregulated promote growth interact system, provide future insights into immunotherapeutic treatment various malignancies.

Language: Английский

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Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 7, 2024

Abstract Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer more challenging and may be unresponsive to conventional therapy. Immunotherapy crucial for treating but its resistance a major limitation. tumor microenvironment (TME) vital in modulating immunotherapy response. Various microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), are involved TME modulation cause resistance. This review highlights role stromal microenvironment, including involvement CAF-TAM interaction, alteration metabolism leading failure, other latest strategies, high throughput genomic screening, single-cell spatial omics techniques identifying immune genes regulating emphasizes therapeutic approach overcome through CAF reprogramming, TAM polarization, metabolism, alterations.

Language: Английский

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Regulation of nucleotide metabolism in cancers and immune disorders

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 33(11), P. 950 - 966

Published: March 24, 2023

Language: Английский

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Control of Invasion by Epithelial-to-Mesenchymal Transition Programs during Metastasis

Journal of Clinical Medicine, Journal Year: 2019, Volume and Issue: 8(5), P. 646 - 646

Published: May 10, 2019

Epithelial-to-mesenchymal transition (EMT) programs contribute to the acquisition of invasive properties that are essential for metastasis. It is well established EMT alter cell state and promote behavior. This review discusses how rather than following one specific program, states diverse in their regulation properties. Analysis across a spectrum models using combination approaches has revealed unique features distinct dictate whether tumor cells invade as single or collectively cohesive groups cells. also been shown mode collective invasion determined by nature EMT, with trailblazer-type being capable initiating invasion, whereas have undergone an opportunist-type dependent on extrinsic factors invade. In addition altering intrinsic properties, can influence through non-cell autonomous mechanisms. subpopulations demonstrated EMT-induced drive sibling epithelial populations paracrine signaling remodeling microenvironment. Importantly, variation controlled influences kinetics location

Language: Английский

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Dysregulation of EMT Drives the Progression to Clinically Aggressive Sarcomatoid Bladder Cancer

Cell Reports, Journal Year: 2019, Volume and Issue: 27(6), P. 1781 - 1793.e4

Published: May 1, 2019

Sarcomatoid urothelial bladder cancer (SARC) displays a high propensity for distant metastasis and is associated with short survival. We report comprehensive genomic analysis of 28 cases SARC 84 conventional carcinoma (UC), the TCGA cohort 408 muscle-invasive cancers serving as reference. SARCs show distinct mutational landscape, enrichment TP53, RB1, PIK3CA mutations. They are related to basal molecular subtype UCs could be divided into epithelial-basal more clinically aggressive mesenchymal subsets on basis TP63 its target gene expression levels. Other analyses reveal that driven by downregulation homotypic adherence genes dysregulation EMT network, nearly half exhibit heavily infiltrated immune phenotype. Our observations have important implications prognostication development effective therapies this highly lethal variant cancer.

Language: Английский

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c‑Myc maintains the self‑renewal and chemoresistance properties of colon cancer stem cells

Oncology Letters, Journal Year: 2019, Volume and Issue: unknown

Published: Feb. 28, 2019

Cancer stem cells (CSCs) are responsible for cancer formation, recurrence and drug resistance. c-Myc, one of the core markers cells, has recently been considered to serve as a link between malignancy 'stemness'. However, precise function c-Myc in colon CSCs is still unclear. In present study, subpopulation expressing CD133 surface phenotype was isolated from human HT-29 cell line, which possess greater tumor sphere-forming efficiency have higher expression 'stemness'-associated genes compared with CD133-negative cells. Furthermore, it demonstrated that highly expressed CD133+ CSCs. Knockdown small interfering RNA can significantly inhibit sphere reduce invasive migratory capacity vitro, suppress tumorigenicity vivo. addition, suggested silencing may sensitize chemotherapy-induced cytotoxicity via downregulation ABCG2 ABCB5. These findings support central role maintaining self-renewing chemoresistant properties

Language: Английский

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A comprehensive review on pyrimidine analogs-versatile scaffold with medicinal and biological potential

Journal of Molecular Structure, Journal Year: 2021, Volume and Issue: 1246, P. 131168 - 131168

Published: July 23, 2021

Language: Английский

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Dysbiosis of Oral Microbiota During Oral Squamous Cell Carcinoma Development

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Feb. 23, 2021

Infection with specific pathogens and alterations in tissue commensal microbial composition are intricately associated the development of many human cancers. Likewise, dysbiosis oral microbiome was also shown to play critical role initiation as well progression cancer. However, there no reports portraying changes community patients Indian subcontinent, which has highest incidence cancer per year, globally. To establish association bacterial squamous cell carcinoma (OSCC) among population, malignant lesions anatomically matched adjacent normal tissues were obtained from fifty well-differentiated OSCC analyzed using 16S rRNA V3-V4 amplicon based sequencing on MiSeq platform. Interestingly, contrast previous studies, a significantly lower diversity observed samples compared counterpart. Overall our study identified Prevotella, Corynebacterium , Pseudomonas Deinococcus Noviherbaspirillum enriched genera, whereas genera including Actinomyces Sutterella Stenotrophomonas Anoxybacillus Serratia notably decreased lesions. Moreover, we demonstrated HPV-16 but not HPV-18 development. In future, additional validation, this panel could directly be applied into clinical diagnostic prognostic workflows for scenario.

Language: Английский

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