Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy DOI Creative Commons
Györgyi Műzes, Ferenc Sípos

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 1130 - 1130

Published: April 8, 2023

The immune system and autophagy share a functional relationship. Both innate adaptive responses involve and, depending on the disease’s origin pathophysiology, it may have detrimental or positive role autoimmune disorders. As “double-edged sword” in tumors, can either facilitate impede tumor growth. regulatory network that influences progression treatment resistance is dependent cell tissue types stages. connection between autoimmunity carcinogenesis has not been sufficiently explored past studies. crucial mechanism two phenomena, play substantial role, though specifics remain unclear. Several modifiers demonstrated beneficial effects models of disease, emphasizing their therapeutic potential as treatments for function microenvironment cells subject intensive study. objective this review to investigate simultaneous genesis malignancy, shedding light both sides issue. We believe our work will assist organization current understanding field promote additional research urgent topic.

Language: Английский

Small molecule inhibition of TFF3 overcomes tamoxifen resistance and enhances taxane efficacy in ER+ mammary carcinoma DOI Open Access
Hui Guo, Yan Qin Tan, Xiaoming Huang

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 579, P. 216443 - 216443

Published: Oct. 17, 2023

Language: Английский

Citations

10
Mitochondrial bioenergetics as a cell fate rheostat for responsive to Bcl-2 drugs: New cues for cancer chemotherapy DOI
Charlotte Palominos, Sebastián Fuentes-Retamal, Juan Pablo Salazar

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 594, P. 216965 - 216965

Published: May 22, 2024

Language: Английский

Citations

3
Targeting BCL2 with Venetoclax Enhances the Efficacy of the KRASG12D Inhibitor MRTX1133 in Pancreatic Cancer DOI Creative Commons
Jeffrey H. Becker, Anastasia E. Metropulos,

Christina Spaulding

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(21), P. 3629 - 3639

Published: Aug. 13, 2024

Abstract MRTX1133 is currently being evaluated in patients with pancreatic ductal adenocarcinoma (PDAC) tumors harboring a KRASG12D mutation. Combination strategies have the potential to enhance efficacy of further promote cell death and tumor regression. In this study, we demonstrated that increased levels proapoptotic protein BIM PDAC cells conferred sensitivity FDA-approved BCL2 inhibitor venetoclax. Combined treatment venetoclax resulted growth suppression 3D cultures. was required for apoptosis induced by combination treatment. Consistently, treated MRTX1133, enhanced vivo. Venetoclax could also resensitize MRTX1133-resistant cultures, established from resistant responded These results provide rationale clinical testing PDAC. Significance: The drug promotes cancer regression adenocarcinoma, providing inhibitors cancer.

Language: Английский

Citations

3
TFF3 facilitates dormancy of anti-estrogen treated ER+ mammary carcinoma DOI Creative Commons

Shu Chen,

Xi Zhang, Basappa Basappa

et al.

Communications Medicine, Journal Year: 2025, Volume and Issue: 5(1)

Published: Feb. 21, 2025

Tumor dormancy is a substantial clinical obstacle in treatment of estrogen receptor positive mammary carcinoma (ER+MC), contributing to drug resistance, metastatic outgrowth, relapse, and consequent mortality. Preclinical models mimicking anti-estrogen-induced ER+MC were generated vivo. Function mechanism-based combination determined the dormancy-like vitro, ex vivo, The display molecular features tumor mass cellular with associated behavior. Both serum cancer tissue expression Trefoil factor 3 (TFF3) are identified as prognostic indicators dormant TFF3 functioning an epigenetically regulated driver dormancy-associated behaviors. BCL2-dependent pro-survival functions coupled enhanced attributes stemness designates actionable target. Moreover, screening small-molecule-inhibitor (AMPC) compounds used clinically treat anti-estrogen-resistant identifies strong synergism between AMPC CDK4/6 inhibitors models. results concomitant suppression CCND1 kinase activity decrease RB phosphorylation, reduced BCL2 expression, leading both ER + MC cell cycle arrest apoptosis. combined TFF3-CDK4/6 inhibition impedes outgrowth ameliorates host animal survival models, producing complete response percentage animals. Hence, vivo anti-estrogen induced herein, identify this process. may potentially alleviate challenges posed by ER+MC. Estrogen common type breast cancer. It difficult cure cells stop dividing but survive upon leaving dormant. then recurs years or even decades later. To address challenge, mouse developed. was observed that protein, TFF3, chance survival. A found be able mice approach uses experimental inhibit drugs. These suggest possible for people Chen et al. generate (ER+MC) indicator oncogenic exhibiting potential ameliorate outcomes

Language: Английский

Citations

0
The Role of Fibroblast Growth Factors in Viral Replication: FGF-2 as a Key Player DOI Creative Commons

Danial Zareh,

Reyhaneh Nekounam Ghadirli,

Hao Zuo

et al.

IntechOpen eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Fibroblast growth factors (FGFs) are crucial signaling proteins that govern numerous cellular activities, such as proliferation, differentiation, and tissue repair. Recent studies indicate FGFs, particularly FGF-2, pivotal in viral replication by altering the host cell environment to promote survival, replication, immune evasion. Viruses rely on components for their often manipulate pathways, including FGF signaling, optimize growth. Among various FGF-2 (basic FGF) stands out influential due its roles angiogenesis, modulation. This chapter explores molecular processes via which FGFs affect life cycles, highlighting is notably important promoting impact inflammation. Understanding FGF-mediated may offer new therapeutic targets infections.

Language: Английский

Citations

0
Unravelling key signaling pathways for the therapeutic targeting of non-small cell lung cancer DOI

P. Chavan,

Ruchi Pandey,

BHEEMANAGOUDA O. PATIL

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177494 - 177494

Published: March 1, 2025

Language: Английский

Citations

0
Antioxidant activity, antibacterial behavior, and anticancer impact of Egyptian propolis. DOI

Marwa Gomaa,

Khaled M. A. Abdel-Hameed,

Sherien E. Sobhy

et al.

PubMed, Journal Year: 2025, Volume and Issue: 15(1), P. 126 - 138

Published: Jan. 1, 2025

Propolis, a resinous substance produced by bees, exhibits significant phytochemical and biological properties, which have been explored for various therapeutic applications. This study investigates the composition, antioxidant activity, antibacterial efficacy, anticancer potential of ethanolic extracts from three propolis samples (P1, P2, P3). Phytochemical screening was conducted to determine presence bioactive compounds, such as ascorbic acid, saponins, tannins. Antioxidant activity evaluated using phosphomolybdate (PMA) ferric reducing power (FRP) assays. The efficacy against Salmonella Typhimurium Staphylococcus aureus assessed well diffusion method. Cytotoxicity effects were investigated MTT assay on red blood cells (RBCs) carcinoma cell lines (HepG2, MDA, A549). Gene expression analysis performed RT-qPCR assess upregulation immune response genes (P53, Bcl2, Bax, Ca125, C3). revealed considerable quantities tannins in samples. P1 sample exhibited most substantial with FRP values at 62.9 mg/g DM PMA content 20.7 DM. In assays, demonstrated highest inhibitory zones maximum concentration (400 mg/ml), outperforming standard antibiotic treatments. cytotoxicity preserved percentage RBCs hemolysis showed marked lowest viability observed 3.9 µg/ml. genes, particularly MDA HepG2 upon treatment. underscores potent antioxidant, antibacterial, properties propolis, highlighting its natural agent. activities suggest promising applications combating bacterial infections cancer types, warranting further exploration into molecular mechanisms clinical uses.

Language: Английский

Citations

0
Novel Cyanopyrimidine Derivatives as Potential Anticancer Agents DOI Creative Commons

Rania H. Abd El‐Hameed,

Omnia Aly, Mariem El Saeed Mohamed

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(7), P. 1453 - 1453

Published: March 25, 2025

The Bcl-2 family’s anti-apoptotic proteins, particularly Mcl-1, offer a viable avenue for cancer treatment since cells can undergo apoptosis when their selective suppression occurs. Mcl-1 is essential controlling the advancement of cell cycle, as well apoptosis. There constant clinical need more potent treatments breast and ovarian malignancies, even with advancements in discovery anticancer drugs. By synthesizing cyanopyrimidine derivatives that demonstrate both dual inhibitory activity against Bcl-2, successful cycle arrest, our research seeks to contribute development innovative therapeutic medicines. We created number new 6-substituted cyanopyrimidines tested effects on SKOV-3 MCF-7 lines arrest assays.

Language: Английский

Citations

0
Design, Synthesis, and Potent Anticancer Activity of Novel Indole-Based Bcl-2 Inhibitors DOI Open Access
Ahmed M. Almehdi, Sameh S. M. Soliman, Abdel‐Nasser El‐Shorbagi

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14656 - 14656

Published: Sept. 28, 2023

The Bcl-2 family plays a crucial role in regulating cell apoptosis, making it an attractive target for cancer therapy. In this study, series of indole-based compounds, U1–6, were designed, synthesized, and evaluated their anticancer activity against Bcl-2-expressing lines. binding affinity, safety profile, cycle arrest, apoptosis effects the compounds tested. designed exhibited potent inhibitory at sub-micromolar IC50 concentrations MCF-7, MDA-MB-231, A549 Notably, U2 U3 demonstrated highest activity, particularly MCF-7 cells. Respectively, both showed potential BCL-2 inhibition with values 1.2 ± 0.02 11.10 0.07 µM using ELISA assay compared 0.62 0.01 gossypol, employed as positive control. Molecular docking analysis suggested stable interactions compound site through hydrogen bonding, pi-pi stacking, hydrophobic interactions. Furthermore, significant induction arrest G1/S phase. Importantly, displayed favourable profile on HDF human dermal normal fibroblast cells 10-fold greater MDA-MB-231 These findings underscore therapeutic inhibitor provide insights into its molecular mechanisms action.

Language: Английский

Citations

7
PBRM1 loss is associated with increased sensitivity to MCL1 and CDK9 inhibition in clear cell renal cancer DOI Creative Commons

Norman Fultang,

Ashley M. Schwab,

Sophia McAneny-Droz

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 2, 2024

MCL1 is a member of the BCL2 family apoptosis regulators, which play critical role in promoting cancer survival and drug resistance. We previously described PRT1419, potent, inhibitor with anti-tumor efficacy various solid hematologic malignancies. To identify novel biomarkers that predict sensitivity to inhibition, we conducted gene essentiality analysis using dependency data generated from CRISPR/Cas9 cell viability screens. observed clear renal (ccRCC) lines damaging PBRM1 mutations displayed strong on MCL1. (BAF180), chromatin-targeting subunit mammalian pBAF complexes. frequently altered cancers particularly ccRCC ~40% tumors harboring alterations. potent inhibition tumor growth induction by PRT1419 preclinical models PBRM1-mutant but not PBRM1-WT. Depletion PBRM1-WT induced PRT1419. Mechanistically, depletion coincided increased expression pro-apoptotic factors, priming cells for caspase-mediated following inhibition. Increased activity has been as resistance mechanism Sunitinib Everolimus, two approved agents ccRCC. synergized both potently inhibit PBRM1-loss PRT2527, CDK9 depletes MCL1, was similarly efficacious monotherapy combination cells. Taken together, these findings suggest loss associated MCL1i provide rationale evaluation PRT2527 treatment PBRM1-deficient

Language: Английский

Citations

2