ACS Medicinal Chemistry Letters, Год журнала: 2023, Номер 14(10), С. 1334 - 1335
Опубликована: Сен. 20, 2023
Provided herein are novel indazole compounds as TEAD inhibitors, pharmaceutical compositions, use of such in treating cancer, and processes for preparing compounds.
Язык: Английский
Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)
Опубликована: Янв. 23, 2025
Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as major etiological agent, affecting an estimated 50% of the world's population. There has been rapidly expanding knowledge molecular and pathogenetic mechanisms H. over decades. This review summarizes latest research advances to elucidate underlying infection in gastric carcinogenesis. Our investigation reveals complex network involving STAT3, NF-κB, Hippo, Wnt/β-catenin pathways, which are dysregulated caused by pylori. Furthermore, we highlight role inducing oxidative stress, DNA damage, chronic inflammation, cell apoptosis—key cellular events that pave way for Emerging evidence also suggests effect on tumor microenvironment its possible implications immunotherapy. synthesizes current identifies gaps warrant further investigation. Despite progress our previous development pylori-induced cancer, comprehensive pylori's is crucial advancement prevention treatment strategies. By elucidating these mechanisms, aim provide more in-depth insights study pylori-related cancer.
Язык: Английский
Процитировано
5
International Journal of Biological Macromolecules, Год журнала: 2024, Номер 278, С. 134187 - 134187
Опубликована: Авг. 3, 2024
Язык: Английский
Процитировано
8
The Journal of Experimental Medicine, Год журнала: 2024, Номер 221(4)
Опубликована: Фев. 27, 2024
Diffuse-type gastric adenocarcinoma (DGAC) is a deadly cancer often diagnosed late and resistant to treatment. While hereditary DGAC linked CDH1 mutations, the role of CDH1/E-cadherin inactivation in sporadic tumorigenesis remains elusive. We discovered subset patient tumors. Analyzing single-cell transcriptomes malignant ascites, we identified two subtypes: DGAC1 (CDH1 loss) DGAC2 (lacking immune response). displayed distinct molecular signatures, activated DGAC-related pathways, an abundance exhausted T cells ascites. Genetically engineered murine organoids showed that Cdh1 knock-out (KO), KrasG12D, Trp53 KO (EKP) accelerates with evasion compared (KP). also EZH2 as key mediator promoting loss-associated tumorigenesis. These findings highlight DGAC's diversity potential for personalized treatment CDH1-inactivated patients.
Язык: Английский
Процитировано
6
Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)
Опубликована: Ноя. 10, 2023
The Hippo pathway is crucial in organ size control and tumorigenesis. Dysregulation of the Hippo/YAP axis commonly observed gastric cancer, while effective therapeutic targets for are lacking. Identification reliable drug underlying mechanisms that could inhibit activity cancer progression urgently needed.We used several cell lines xenograft models performed immunoblotting, qPCR, vivo studies to investigate function CXCR7 progression.In our current study, we demonstrate membrane receptor (C-X-C chemokine 7) an important modulator axis. activation stimulate through vitro vivo, pharmaceutical inhibition via ACT-1004-1239 block tumorigenesis cancer. Molecular revealed dephosphorylate YAP facilitate nuclear accumulation transcriptional functions G-protein Gαq/11 Rho GTPase activate activity. Interestingly, ChIP assays showed bind promoter region its gene transcription, which indicates both upstream signalling downstream target cancer.In general, identified a novel positive feedback loop between axis, blockade be plausible strategy
Язык: Английский
Процитировано
11
Journal of Biological Chemistry, Год журнала: 2024, Номер 300(6), С. 107311 - 107311
Опубликована: Апрель 22, 2024
The Hippo signaling pathway plays an essential role in organ size control and tumorigenesis. Loss of signal hyper-activation the downstream oncogenic YAP are commonly observed various types cancers. We previously identified STRN3-containing PP2A phosphatase as a negative regulator MST1/2 kinases (i.e., Hippo) gastric cancer (GC), opening possibility selectively targeting PP2Aa-STRN3-MST1/2 axis to recover against cancer. Here, we further discovered 1) disulfiram (DSF), FDA-approved drug, which can similarly block binding STRN3 core enzyme 2) CX-6258 (CX), chemical inhibitor, that disrupt interaction between MST1/2, both allowing reactivation activity inhibit GC. More importantly, found these two compounds, via kinase-dependent manner, DNA repair sensitize GC towards chemotherapy. In addition, thiram, structural analog DSF, function cell proliferation or enhance chemotherapy sensitivity. Interestingly, inclusion copper ion enhanced such effects DSF thiram on treatment. Overall, this work demonstrated pharmacological by drug compounds potently for tumor
Язык: Английский
Процитировано
4
Helicobacter, Год журнала: 2024, Номер 29(4)
Опубликована: Июль 1, 2024
ABSTRACT Background Integrin‐linked kinase (ILK) is crucial in solid tumors by regulating the Hippo‐Yes‐associated protein 1 (YAP) pathway. This study aimed to uncover how Helicobacter pylori influences ILK levels and its role YAP during H. ‐induced gastric cancer. Materials Methods GES‐1 cells with stable Ilk knockdown overexpression a mouse carcinogenesis model for infection were constructed. And ILK, phosphorylated mammalian STE20‐like (MST1), large tumor suppressor (LATS1; S909, T1079), (S109, S127) detected cells, mice western blotting, as well fluorescence intensity of assayed immunofluorescence. downstream genes Igfbp4 Ctgf , pathological changes necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6), interleukin‐1beta (IL‐1β), nitric oxide (NO) tissues real‐time PCR, H&E, ELISA assays. Results In this study, exhibited significantly higher MST1, LATS1, YAP, increased nuclei cells. Conversely, showed opposite results. led decreased epithelial but cancer cell lines (MGC803, SGC7901) mice. Treatment inhibitor OST‐T315 elevated MST, levels, inhibited mRNA at 44, 48 week‐aged also reduced release TNF‐α, IL‐6, IL‐1β, NO, progression caused N ‐Nitroso‐ ‐methylurea (NMU) treatment. Conclusion Upon initiation tumorigenesis signals, increases suppresses Hippo signaling, thereby promoting activation progression. can serve potential prevention target impede
Язык: Английский
Процитировано
2
Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12
Опубликована: Дек. 10, 2024
Chronic atrophic gastritis (CAG) is a prevalent digestive system disease characterized by atrophy of the gastric mucosa and disappearance inherent glands. According to theory Correa’s cascade, CAG an important pathological stage in transformation from normal condition carcinoma. In recent years, global incidence has been increasing due pathogenic factors, including Helicobacter pylori infection, bile reflux, consumption processed meats. this review, we comprehensively described etiology clinical diagnosis CAG. We focused on elucidating regulatory mechanisms promising therapeutic targets CAG, with expectation providing insights theoretical support for future research
Язык: Английский
Процитировано
2
Translational Oncology, Год журнала: 2024, Номер 46, С. 101971 - 101971
Опубликована: Май 25, 2024
Cholangiocarcinoma (CCA) is a devastating malignancy characterized by aggressive tumor growth and limited treatment options. Dysregulation of the Hippo signaling pathway its downstream effector, Yes-associated protein (YAP), has been implicated in CCA development progression. In this study, we investigated effects Isoalantolactone (IALT) on cells to elucidate effect YAP activity potential clinical significance. Our findings demonstrate that IALT exerts cytotoxic effects, induces apoptosis, modulates SNU478 cells. We further confirmed involvement canonical generating LATS1/LATS2 knockout cells, highlighting dependence IALT-mediated apoptosis phosphorylation Hippo-LATS axis. addition, suppressed cell migration, partially dependent YAP-TEAD activity. These results provide insights into therapeutic targeting rationale for developing YAP-targeted therapies challenging malignancy.
Язык: Английский
Процитировано
1
Developmental & Comparative Immunology, Год журнала: 2024, Номер 161, С. 105242 - 105242
Опубликована: Авг. 14, 2024
Язык: Английский
Процитировано
0
ACS Medicinal Chemistry Letters, Год журнала: 2023, Номер 14(9), С. 1152 - 1153
Опубликована: Авг. 22, 2023
Provided herein are novel compounds as TEAD inhibitors, pharmaceutical compositions, use of such in treating cancer, and processes for preparing compounds.
Язык: Английский
Процитировано
1