The Immune Landscape and Its Potential for Immunotherapy in Advanced Biliary Tract Cancer DOI Creative Commons
Ari Santoso, Iris J. M. Levink, Rille Pihlak

и другие.

Current Oncology, Год журнала: 2024, Номер 32(1), С. 24 - 24

Опубликована: Дек. 31, 2024

Biliary tract cancers (BTC) are a highly heterogeneous group of at the genomic, epigenetic and molecular levels. The vast majority patients initially present an advanced (unresectable) disease stage due to lack symptoms aggressive tumour biology. Chemotherapy has been mainstay treatment in with BTC but survival outcomes prognosis remain poor. addition immune checkpoint inhibitors (ICI) chemotherapy have shown only marginal benefit over alone complex microenvironment these cancers. This review appraises our current understanding landscape BTC, including emerging transcriptome-based classifications, highlighting mechanisms evasion resistance ICI their therapeutic implications. It describes shifting paradigm from traditional immunotherapy combinations as well potential biomarkers for predicting response ICI.

Язык: Английский

Chemoresistance mechanisms to 5-Fluorouracil and reversal strategies in lung and breast cancer DOI Creative Commons
Chunge Zhong, Shengnan Wang, Wenjie Jiang

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 19, 2025

Язык: Английский

Процитировано

1

Overview of Wnt/β-Catenin Pathway and DNA Damage/Repair in Cancer DOI Creative Commons
Silvina B. Nadin, F. Darío Cuello-Carrión,

Niubys Cayado-Gutiérrez

и другие.

Biology, Год журнала: 2025, Номер 14(2), С. 185 - 185

Опубликована: Фев. 11, 2025

The Wnt/β-catenin pathway takes part in important cellular processes tumor cells, such as gene expression, adhesion, and survival. canonical is activated several tumors, β-catenin its major effector. union of Wnt to the co-receptor complex causes inhibition GSK3β activity, thus preventing phosphorylation degradation β-catenin, which accumulates cytoplasm, subsequently be transported nucleus associate with transcription factors. relationship between DNA damage/repair mechanisms has been a focus for last few years. Studying network interactions proteins become successful research field. This review provides an overview participation their future implications targets cancer therapy.

Язык: Английский

Процитировано

0

Lipopolysaccharide-Induced Inflammatory Response and Its Prominent Suppression by Paspalum thunbergii Extract DOI Open Access

Bin Ha,

Ji-Hye Kang,

Do Hyun Kim

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1611 - 1611

Опубликована: Фев. 13, 2025

The extract of Paspalum thunbergii, a native perennial herb in Korea belonging to the rice family, was investigated for its anti-inflammatory activity and underlying mechanisms driving effects. Fifteen chemical components P. thunbergii extract, including rosmarinic acid isoquercitrin, were identified using LC-MS. showed antioxidative through DPPH ABTS cation radical scavenging activity. significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production macrophage RAW 264.7 cells. expression lipopolysaccharide-induced iNOS COX-2, which are inflammation-related enzymes. To explore mechanism, levels signal proteins related MAPK, NF-κB, JAK/STAT, Wnt/β-catenin signaling measured. As result, p-p38, p-JNK increased by LPS Additionally, it decreased LPS-induced p-IKKβ p-NF-κB p65 prevented migration into nucleus caused LPS. Notably, p-JAK1, p-STAT3, Wnt 3α, β-catenin, p-GSK-3β protein expressions also inhibited. Therefore, prominent may be via pathway.

Язык: Английский

Процитировано

0

Advances in Targeted and Chemotherapeutic Strategies for Colorectal Cancer: Current Insights and Future Directions DOI Creative Commons

Salique H. Shaham,

Puneet Vij, Manish K. Tripathi

и другие.

Biomedicines, Год журнала: 2025, Номер 13(3), С. 642 - 642

Опубликована: Март 5, 2025

Colorectal cancer (CRC) remains one of the leading causes cancer-related mortality worldwide, necessitating continuous evolution therapeutic approaches. Despite advancements in early detection and localized treatments, metastatic colorectal (mCRC) poses significant challenges due to low survival rates resistance conventional therapies. This review highlights current landscape CRC treatment, focusing on chemotherapy targeted Chemotherapeutic agents, including 5-fluorouracil, irinotecan, oxaliplatin, have significantly improved but face limitations such as systemic toxicity resistance. Targeted therapies, leveraging mechanisms like VEGF, EGFR, Hedgehog pathway inhibition, offer promising alternatives, minimizing damage healthy tissues while enhancing precision. Furthermore, future directions treatment include exploring innovative targets Wnt/β-catenin, Notch, TGF-β pathways, alongside IGF/IGF1R inhibition. These emerging strategies aim address drug improve patient outcomes. emphasizes importance integrating molecular insights into development, advocating for a more personalized approach combat CRC’s complexity heterogeneity.

Язык: Английский

Процитировано

0

Novel De Novo BRCA2 Variant in an Early-Onset Ovarian Cancer Reveals a Unique Tumor Evolution Pathway DOI Open Access
Gianmaria Miolo, Giovanni Canil, Maurizio Polano

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 2295 - 2295

Опубликована: Март 5, 2025

Ovarian cancer (OC) is a highly heterogeneous malignancy, often characterized by complex genomic alterations that drive tumor progression and therapy resistance. In this paper, we report novel de novo BRCA2 germline variant NM_000059.3:c.(8693_8695delinsGT) associated with early-onset OC featured two regions differential MMR (Mismatch Repair) gene expression. To date, only six cases of variants have been reported, none which were high-grade serous OC. The immunohistochemical analysis genes revealed distinct areas, separated clear topographic boundary, the expression MLH1 PMS2 proteins. Seventy-five percent tissue showed positivity, while remaining 25% exhibited complete absence expression, underscoring spatial variability in within tumor. Integrated comparative profiling identified several features genetic as loss heterozygosity (LOH) involved genes, along significantly higher mutational burden area lacked indicating its further molecular evolution. following acquired: c.6572C>T NOTCH2, c.1852C>T BCL6, c.191A>T INHBA, c.749C>T CUX1, c.898C>A FANCG, c.1712G>C KDM6A. proteomic profiles defects DNA repair pathways, well significant extracellular matrix (ECM). proteins repair, particularly those Base Excision Repair (BER), highlights critical role defective mechanisms driving instability. Furthermore, ECM components, such collagen isoforms, Fibrillin-1, EMILIN-1, Prolargin, Lumican, found to be expressed MLH1/PMS2-deficient area, suggesting connection between deficiencies, remodeling, progression. Thus, identification sheds light on poorly understood interplay deficiencies remodeling OC, providing new insights into their dual shaping evolution potential targets for therapeutic strategies.

Язык: Английский

Процитировано

0

Protective effects of sesamol against cigarette smoke toxicity on the blood-brain barrier DOI Creative Commons

Ildem Koru,

Belkıs Atasever-Arslan

BMC Complementary Medicine and Therapies, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 22, 2025

Cigarette smoke comprises nicotine, reactive oxygen species (ROS), and carcinogens, which can induce oxidative stress inflammation, leading to disruption of the blood-brain barrier. This study utilized cigarette extract (CSE) in an vitro model barrier (BBB). Sesamol is a phenolic compound derived from Sesamum indicum L. Its potential reduce inflammation provide protection was also examined. As result study, it found that CSE significantly increases permeability by degrading BBB, whereas protective effect observed sesamol-incubated group within BBB model. While + does not entirely prevent damage induced barrier, exhibit mitigating on damage. In HUVEC cells, significant decrease IL-8 levels sesamol groups. T98G were elevated group, while reduction TNF-α went up but down groups cells. Furthermore, IL-6 increased both noted cells treatment. The increase due indicates inflammatory response. It contribute enhanced permeability. result, reduced caused controlling IL-8, IL-6, TNF-α. molecule may serve therapeutic role diminishing protecting

Язык: Английский

Процитировано

0

The Importance of Cancer Stem Cells and Their Pathways in Endometrial Cancer: A Narrative Review DOI Creative Commons
Laura Caravia, Melinda-Ildiko Mitranovici,

Ioan Emilian Oală

и другие.

Cells, Год журнала: 2025, Номер 14(8), С. 594 - 594

Опубликована: Апрель 14, 2025

Endometrial cancer is one of the most common malignancies seen in women developed countries. While patients early stages this show better responses to surgery, adjuvant hormonal therapy, and chemotherapy, with recurrence treatment resistance. Researchers have recently focused on stem cells (CSCs) gynecologic general but also specifically endometrial cancer. CSCs been investigated because their resistance conventional therapies, such as chemo- radiotherapy, ability induce progression malignancy. The activation alternative pathways, WNT, PI3K, NF-kB, or NOTCH, could be basis acquisition these abilities CSCs. Their specific markers signaling pathways targets for In article, we discuss importance obtaining a understanding molecular role CSCs, aiming discover more therapeutic approaches.

Язык: Английский

Процитировано

0

The E3 Ubiquitin Ligase Trip12 attenuates Wnt9a/Fzd9b signaling during hematopoietic stem cell development DOI Creative Commons

Jessica Ensing,

Amber D. Ide,

Carla Gilliland

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 25, 2024

Abstract Wnt signaling is essential for both the development and homeostasis of diverse cellular lineages, including hematopoietic stem cells. Organism-wide, signals are tightly regulated, as overactivation pathway can lead to tumorigenesis. Although numerous ligands Frizzled (Fzd) receptors exist, how particular Wnt/Fzd pairings established their regulated poorly understood. We have previously identified requirements cognate pairing Wnt9a Fzd9b early cell proliferation. However, specific governing activation, but equally important, molecular mechanisms required turn signal ‘off,’ unknown. Here, we show that E3 ubiquitin ligase Trip12 (thyroid hormone receptor interactor 12) specifically ubiquitinate third intracellular loop at K437, targeting it lysosomal degradation. In contrast other ligases described regulate surface availability multiple Fzds broadly, our data indicate selective Fzd9b. further demonstrate this occurs through ubiquitination K437 in loop, ultimately leading a decrease Wnt9a/Fzd9b impacts proliferation zebrafish. Our results point driving different Fzd receptors. Determining abundance membrane will be critical developing therapies human intervention. One sentence summary ubiquitinates

Язык: Английский

Процитировано

0

The Immune Landscape and Its Potential for Immunotherapy in Advanced Biliary Tract Cancer DOI Creative Commons
Ari Santoso, Iris J. M. Levink, Rille Pihlak

и другие.

Current Oncology, Год журнала: 2024, Номер 32(1), С. 24 - 24

Опубликована: Дек. 31, 2024

Biliary tract cancers (BTC) are a highly heterogeneous group of at the genomic, epigenetic and molecular levels. The vast majority patients initially present an advanced (unresectable) disease stage due to lack symptoms aggressive tumour biology. Chemotherapy has been mainstay treatment in with BTC but survival outcomes prognosis remain poor. addition immune checkpoint inhibitors (ICI) chemotherapy have shown only marginal benefit over alone complex microenvironment these cancers. This review appraises our current understanding landscape BTC, including emerging transcriptome-based classifications, highlighting mechanisms evasion resistance ICI their therapeutic implications. It describes shifting paradigm from traditional immunotherapy combinations as well potential biomarkers for predicting response ICI.

Язык: Английский

Процитировано

0