The Prostate, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 11, 2024
The transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) plays a role in carcinogenesis is involved processes, such as proliferation, differentiation, drug resistance immunosuppression. STAT3 can be activated by phosphorylation tyrosine at position 705 (pSTAT3
Язык: Английский
Environmental Toxicology, Год журнала: 2024, Номер 39(6), С. 3356 - 3366
Опубликована: Март 5, 2024
Abstract Melanoma is the most lethal skin malignancy. Fucoxanthin a marine carotenoid with significant anticancer activities. Intriguingly, Fucoxanthin's impact on human melanoma remains elusive. Signal Transducer and Activator of Transcription 3 (STAT3) represents promising target in cancer therapy due to its persistent activation various cancers, including melanoma. Herein, we revealed that cytotoxic cell lines A2758 A375 while showing limited cytotoxicity normal melanocytes. Apoptosis primary reason for cytotoxicity, as pan‐caspase inhibitor z‐VAD‐fmk drastically abrogated Fucoxanthin‐elicited clonogenicity blockage. Besides, downregulated tyrosine 705‐phosphorylated STAT3 (p‐STAT3 (Y705)), either inherently present cells or inducible by interleukin 6 (IL‐6) stimulation. Notably, ectopic expression STAT3‐C, dominant‐active mutant, abolished apoptosis inhibition, supporting pivotal role blockage cytotoxicity. Moreover, lowered BCL‐xL levels blocking activation, rescued from Fucoxanthin‐induced killing. Lastly, was found diminish JAK2 dual phosphorylation at residues 1007 1008 cells, suggesting impairs signaling activation. Collectively, first evidence selectively against sparing Mechanistically, targets JAK2/STAT3/BCL‐xL antiapoptotic axis provoke death. This discovery implicates potential application chemopreventive therapeutic strategy management.
Язык: Английский
Процитировано
2
Phytomedicine, Год журнала: 2024, Номер 128, С. 155497 - 155497
Опубликована: Фев. 28, 2024
Colorectal cancer (CRC) is a significant public health issue, ranking as one of the predominant types globally in terms incidence. Intriguingly, Arenobufagin(Are), compound extracted from toad venom, has demonstrated potential to inhibit tumor growth effectively. This study aimed explore Are's molecular targets and unravel its antitumor mechanism CRC. Specifically, we were interested impact on immune checkpoint modulation correlations with HSP90β-STAT3-PD-L1 axis activity. We investigated vivo effects Are by constructing colorectalcancer subcutaneous xenograft mouse model. Subsequently, employed single-cell multi-omics technology which inhibits colorectal cancer. Utilizing Target-responsive accessibility profiling (TRAP) technology, identified heatshock protein 90p (HSP90β) direct target Are, confirmed this through microscale thermophoresis experiment (MST). Further downstream mechanisms explored techniques such co-immunoprecipitation, Western blotting, qPCR, immunofluorescence. Concurrently, arrived at same research conclusion organoid level co-cultivating cells. observed that PD-Ll expression CRC xenografts low concentrations. Moreover, TRAP revealed HSP90p's significantly decreasedupon binding. decrease activity HSP908-STAT3-PD-Ll following low-concentration treatment vivo. The PDO analysis showed improved enrichment lymphocytes, particularly T cells, PDOs treatment. Contrary previous focusing cytotoxicity Arenobufagin towards our findings indicate it can also lower concentrations checkpoints. unveils novel anti-tumor stimulates contemplation dose-response relationship natural products, beneficial for clinical translational application Arenobufagin.
Язык: Английский
Процитировано
2
World Journal of Gastrointestinal Oncology, Год журнала: 2024, Номер 16(5), С. 1705 - 1724
Опубликована: Май 7, 2024
Colorectal cancer (CRC) remains one of the most commonly diagnosed and deadliest types worldwide. CRC displays a desmoplastic reaction (DR) that has been inversely associated with poor prognosis; less DR is better prognosis. This generates excessive connective tissue, in which cancer-associated fibroblasts (CAFs) are critical cells form part tumor microenvironment. CAFs directly involved tumorigenesis through different mechanisms. However, their role immunosuppression not well understood, precise signal transducers activators transcription (STATs) mediating CAF activity unclear. Among myriad chemical biological factors affect CAFs, cytokines mediate function by activating STAT signaling pathways. Thus, harmful effects favoring growth invasion may be modulated using inhibitors. Here, we analyze impact STATs on immunoregulatory role.
Язык: Английский
Процитировано
2
Acta Pharmacologica Sinica, Год журнала: 2024, Номер 46(1), С. 184 - 195
Опубликована: Авг. 28, 2024
Язык: Английский
Процитировано
2
Phytomedicine, Год журнала: 2024, Номер 135, С. 156022 - 156022
Опубликована: Сен. 7, 2024
Язык: Английский
Процитировано
2
Microbial Biotechnology, Год журнала: 2024, Номер 17(11)
Опубликована: Ноя. 1, 2024
Abstract Despite the great potential of DNA vaccines for a broad range applications, ranging from prevention infections, over treatment autoimmune and allergic diseases to cancer immunotherapies, implementation such therapies clinical is far behind expectations up now. The main reason poor immunogenicity in humans. Consequently, improvement performance vivo required. This mini‐review provides an overview current state various strategies enhance immunogenic vaccines, including (i) optimization construct itself regarding size, nuclear transfer transcriptional regulation; (ii) use appropriate adjuvants; (iii) improved delivery, example, by careful choice administration route, physical methods as electroporation nanomaterials that may allow cell type‐specific targeting. Moreover, combining nanoformulated with other immunotherapies prime‐boost help success treatment.
Язык: Английский
Процитировано
2
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Сен. 8, 2024
Abstract Immune checkpoint inhibitors (ICIs), also called immune blockers, are a promising category of targeted therapy for solid tumors. Predicting which patients will respond to ICI remains an open problem under active investigation. This paper adds this effort by developing modular pipeline the discovery biomarkers from tumor RNA-sequencing data. We contextualize gene expression measurements using protein-protein interaction (PPI) network and use notion graph curvature find (pairs of) genes in PPI that could serve as potential biomarkers. Our candidate evaluated extensive literature search transfer learning experiments. provide harmonized collection drug-specific markers found through rank aggregation we believe merit further study.
Язык: Английский
Процитировано
1
International Journal of Pharmaceutics, Год журнала: 2024, Номер 665, С. 124689 - 124689
Опубликована: Сен. 13, 2024
Язык: Английский
Процитировано
1
Translational Pediatrics, Год журнала: 2024, Номер 13(2), С. 271 - 287
Опубликована: Фев. 1, 2024
Background: Kawasaki disease (KD) often complicates coronary artery lesions (CALs). Despite the established significance of STAT3 signaling during acute phase KD and signal transducer activator transcription 3 (STAT3) being closely related to CALs, it remains unknown whether how was regulated by ubiquitination pathogenesis.
Язык: Английский
Процитировано
0
International Journal of Pharmaceutics, Год журнала: 2024, Номер unknown, С. 124845 - 124845
Опубликована: Окт. 1, 2024
Язык: Английский
Процитировано
0