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Mitogen‐Activated Protein Kinase Kinase Kinase 1 (MAP3K1) is overexpressed in gliomas; however, its clinical significance, biological functions, and underlying molecular mechanisms remain unclear. Abnormal overexpression of MAP3K1 in glioma is strongly associated with unfavourable clinicopathological characteristics and disease progression. MAP3K1 could potentially serve as a reliable diagnostic and prognostic biomarker for glioma. MAP3K1 silencing suppressed the migration but had no effect on the proliferation and cell death of Glioblastoma Multiforme (GBM) cells. MAP3K1 knockdown exacerbated the temozolomide (TMZ) induced inhibition of glioma cell proliferation and death of GBM cells. In addition, MAP3K1 knockdown combined with TMZ treatment significantly inhibited the growth and increased cell death in organoids derived from GBM patients. MAP3K1 knockdown reversed TMZ resistance of GBM in intracranial glioma model. In terms of molecular mechanisms, the phosphorylation level of ERK was significantly decreased by MAP3K1 silencing. No significant change in the JNK pathway was found in MAP3K1‐silenced GBM cells. Inhibition of ERK phosphorylation suppressed the migration and enhanced the TMZ sensibility of GBM cells. MAP3K1 was correlated with the immune infiltration in glioma. MAP3K1 could facilitate the migration and TMZ resistance of GBM cells through MEK/ERK signalling. [ABSTRACT FROM AUTHOR]

Despite advancements in cancer research, epithelial ovarian cancer remains a leading threat to women’s health with a low five-year survival rate of 48%. Prognosis for advanced cases, especially International Federation of Gynecology and Obstetrics (FIGO) III-IV, is poor. Standard care includes surgical resection and platinum-based chemo, but 70-80% face recurrence and chemoresistance. In recent years, three- dimensional (3D) cancer models, especially patients-derived organoids (PDOs), have revolutionized cancer research for personalized treatment. By transcending the constraints of conventional models, organoids accurately recapitulate crucial morphological, histological, and genetic characteristics of diseases, particularly in the context of ovarian cancer. The extensive potential of ovarian cancer organoids is explored, spanning from foundational theories to cutting-edge applications. As potent preclinical models, organoids offer invaluable tools for predicting patient treatment responses and guiding the development of personalized therapeutic strategies. Furthermore, in the arena of drug evaluation, organoids demonstrate their unique versatility as platforms, enabling comprehensive testing of innovative drug combinations and novel candidates, thereby pioneering new avenues in pharmaceutical research. Notably, organoids mimic the dynamic progression of ovarian cancer, from inception to systemic dissemination, shedding light on intricate and subtle disease mechanisms, and providing crucial insights. Operating at an individualized level, organoids also unravel the complex mechanisms underlying drug resistance, presenting strategic opportunities for the development of effective treatment strategies. This review summarizes the emerging role of ovarian cancer organoids, meticulously cultivated cellular clusters within threedimensional models, as a groundbreaking paradigm in research. [ABSTRACT FROM AUTHOR]

Background: Lung cancer remains the foremost reason of cancer‐related mortality, with invasion and metastasis profoundly influencing patient prognosis. N‐acetyltransferase 10 (NAT10) catalyzes the exclusive N (4)‐acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role in non‐small cell lung cancer (NSCLC) invasion and metastasis remains unclear. Our study delves into the clinical significance and functional aspects of NAT10 in NSCLC. Methods: We investigated NAT10's clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT‐PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10's effects. A series of assays were carried out, including CCK‐8, colony formation, wound healing, and transwell assays, to elucidate NAT10's role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient‐derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings. Results: Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E‐cadherin level whereas decreased N‐cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial‐mesenchymal transition (EMT) pathway. Conclusions: Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition. [ABSTRACT FROM AUTHOR]

Abstract Background Lung cancer remains the foremost reason of cancer‐related mortality, with invasion and metastasis profoundly influencing patient prognosis. N‐acetyltransferase 10 (NAT10) catalyzes the exclusive N (4)‐acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role in non‐small cell lung cancer (NSCLC) invasion and metastasis remains unclear. Our study delves into the clinical significance and functional aspects of NAT10 in NSCLC. Methods We investigated NAT10's clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT‐PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10's effects. A series of assays were carried out, including CCK‐8, colony formation, wound healing, and transwell assays, to elucidate NAT10's role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient‐derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings. Results Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E‐cadherin level whereas decreased N‐cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial‐mesenchymal transition (EMT) pathway. Conclusions Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition.

Nanocatalytic medicine triggering in situ catalytic reactions has been considered as a promising strategy for tumor-selective therapeutics. However, the targeted distribution of nanocatalysts was still low, considering the absence of targeting propulsion capability. Here, encouraged by the fast-developing controllable microrobotics for targeting delivery, a sunflower-like nanocatalytic active swarm (SNCAS) controlled by a three-dimensional (3D) magnetic field was proposed for synergistic tumor-selective and magnetic-actively tumor-targeting therapeutics. Furthermore, a patient-derived renal cancer cell 3D organoid was utilized for the verification of the effective tumor therapeutic outcomes. Under the targeted control of 3D magnetic field, the multiple cascade catalytic efficiency of SNCAS based on Fenton reaction was evaluated, resulting in efficient tumor cell apoptosis and death. For the patient-derived organoid treatment, the SNCAS presented significant lethality toward 3D organoid structure to induce cell apoptosis with the collapse of organoid morphology. The targeting efficiency was further enhanced under the magnetic-controllable of SNCAS. Overall, empowered by the magnetic control technology, the synergistic therapeutic strategy based on controllable swarm combined active targeting and tumor-specific catalytic nanomedicine has provided a novel way for advanced cancer therapy. Meanwhile, 3D patient-derived organoids were proved as a powerful tool for the effectiveness verification of nanocatalytic medicine. [ABSTRACT FROM AUTHOR]

Despite advancements in cancer research, epithelial ovarian cancer remains a leading threat to women's health with a low five-year survival rate of 48%. Prognosis for advanced cases, especially International Federation of Gynecology and Obstetrics (FIGO) III-IV, is poor. Standard care includes surgical resection and platinum-based chemo, but 70-80% face recurrence and chemoresistance. In recent years, three- dimensional (3D) cancer models, especially patients-derived organoids (PDOs), have revolutionized cancer research for personalized treatment. By transcending the constraints of conventional models, organoids accurately recapitulate crucial morphological, histological, and genetic characteristics of diseases, particularly in the context of ovarian cancer. The extensive potential of ovarian cancer organoids is explored, spanning from foundational theories to cutting-edge applications. As potent preclinical models, organoids offer invaluable tools for predicting patient treatment responses and guiding the development of personalized therapeutic strategies. Furthermore, in the arena of drug evaluation, organoids demonstrate their unique versatility as platforms, enabling comprehensive testing of innovative drug combinations and novel candidates, thereby pioneering new avenues in pharmaceutical research. Notably, organoids mimic the dynamic progression of ovarian cancer, from inception to systemic dissemination, shedding light on intricate and subtle disease mechanisms, and providing crucial insights. Operating at an individualized level, organoids also unravel the complex mechanisms underlying drug resistance, presenting strategic opportunities for the development of effective treatment strategies. This review summarizes the emerging role of ovarian cancer organoids, meticulously cultivated cellular clusters within three-dimensional models, as a groundbreaking paradigm in research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Yin and Li.)

The article focuses on exploring a potential pro-immunogenic treatment for triple-negative breast cancers (TNBC) by combining the inhibition of alternative splicing with EZH2 activity, aiming to enhance tumor immunogenicity and potentially improve therapeutic outcomes for TNBC patients.