- |||||||||| Journal, Gene therapy: NF-?B-activated oncogene inhibition strategy for cancer gene therapy. (Pubmed Central) - Nov 16, 2024
Based on the scRNA-seq data, we observed that HOPE could activate the immune system and decrease the proportion of cancer cells, particularly reducing the stemness of cancer cells. This study elucidates an important role of HOPE in inhibiting cancer cell growth both in vitro and in vivo, additionally provides a novel therapeutic technology for cancer gene therapy.
- |||||||||| Journal: Self-priming of Plk1 binding to BubR1 ensures accurate mitotic progression. (Pubmed Central) - Nov 15, 2024
Increasing the binding affinity towards Plk1 and PP2A/B56 in BubR1 through protein engineering bypasses the requirement of T600/T608 phosphorylation for mitotic progression. These results reveal a new layer of regulation for accurate mitotic progression.
- |||||||||| Activation of polo-like kinase 1 contributes to selective motor neuron vulnerability in familial ALS (Poster Hall at the Palais de Congres Montreal; 517b/c) - Nov 7, 2024 - Abstract #ALSMND2024ALS_MND_479;
Furthermore, stress granules dynamics were less affected in cortical neurons and mutant FUS cortical neurons exhibited less axonal organelle trafficking disturbance than spinal MNs. RNA sequencing of FUS ALS cortical and spinal motor neurons revealed basic differences in their transcriptomes.
- |||||||||| Nerlynx (neratinib) / Puma
Journal, Combination therapy: Biomimetic Modification of siRNA/Chemo Drug Nanoassemblies for Targeted Combination Therapy in Breast Cancer. (Pubmed Central) - Nov 7, 2024 To overcome these obstacles, we have engineered cyclic Arg-Gly-Asp (cRGD)-modified red blood cell membrane (RBCm)-coated multidrug nanocomplexes, which were self-assembled from the Polo-like kinase 1 siRNA (siPlk1) and an irreversible tyrosine kinase inhibitor neratinib targeted to human epidermal growth factor receptor 2 (HER2) overexpressed in breast cancer...The cRGD-modified red blood cell membranes coated on the surface of the multidrug nanoparticles could enhance drug stability in circulation and tumor accumulation. This targeted combinational therapy significantly enhanced the antitumor efficiency in HER2-positive breast cancer in vitro and in vivo.
- |||||||||| ASXL1 Mutations in AML Are Associated with a Distinct Epigenetic State Which Highlights Vulnerabilities to Specific Epigenetic-Targeted Agents (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_5817;
Notably, compared to parental cells, OCIAML3 ASXL1 Y591* cells exhibited reduced sensitivity to standard anti-AML chemotherapeutic agents, including cytarabine, etoposide and daunorubicin...Our findings also demonstrate and confirm that mtASXL1-expressing AML cells exhibited increased sensitivity to BETi (pelabresib or birabresib)...Importantly, in the NSG mice engrafted with luciferized OCIAML3 ASXL1 Y591*, monotherapy with NEO2734 (5 mg/kg QD), pelabresib (30 mg/kg QD) or SEL120-34A (40 mg/kg QD), compared to vehicle control, significantly reduced AML burden. Collectively these findings highlight previously uncharacterized biologic effects of the presence of mtASXL1 and support the rationale for further evaluating AML therapies incorporating BETi, HAT-BETi or inhibitor of mediator kinase.
- |||||||||| MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute, tegavivint (BC2059) / Iterion Therap
Targeting the DNA Damage Response through TBL1X in Mantle Cell Lymphoma (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_5180; Ongoing work is focused on delineation of the mechanism through which TBL1X controls RAD51 stability. We believe these findings support further exploration of targeting of TBL1X in MCL with tegavivint.
- |||||||||| Roles of TET2 Loss in B Cell Transformation (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_4839;
The resulting cell death vulnerabilities may be overcome by BCL2 network remodeling during transformation, as the ultimately transformed TET2 LOF B cell lymphomas show robust expression of the pro-survival BCL2 family protein BCLX. Altogether, our studies provide evidence that TET2 LOF promotes genomic instability along with BCL2 network rewiring, fueling B cell transformation.
- |||||||||| Journal: Genetic Markers of Spina Bifida in an Indian Cohort. (Pubmed Central) - Oct 31, 2024
The genetic landscape of the spina bifida in an Indian cohort is diverse compared to that reported from other parts of the world. A comprehensive catalog of single-nucleotide variants in the etiopathogenesis of the spina bifida on a background of the Familial Neural Tube Defects Panel has been generated.
- |||||||||| Journal: Regulation of minimal spindle midzone organization by mitotic kinases. (Pubmed Central) - Oct 30, 2024
Dephosphorylation of CDK1-phosphorylated PRC1 is required and sufficient to trigger the reorganization of a minimal anaphase midzone in the presence of the midzone length controlling kinesin KIF4A. These results demonstrate how phosphorylation-controlled affinity changes regulate the architecture of active microtubule networks, providing new insight into the mechanistic underpinnings of the cell cycle-driven reorganization of the central spindle during mitosis.
- |||||||||| Journal, IO biomarker: Integrative analysis of anoikis-related genes prognostic signature with immunotherapy and identification of CDKN3 as a key oncogene in lung adenocarcinoma. (Pubmed Central) - Oct 29, 2024
The pivotal role of CDKN3 in LUAD was confirmed through qRT-PCR and gene knockout experiments, demonstrating that CDKN3 knockdown inhibits tumor cell proliferation, migration, and invasion. Additionally, we constructed a ceRNA network involving CDKN3/hsa-miR-26a-5p/SNHG6, LINC00665, DUXAP8, and SLC2A1/hsa-miR-218-5p/RNASEH1-AS1, providing new insights for personalized and immune therapy decisions in LUAD patients.
- |||||||||| citalopram / Generic mfg.
Biomarker, Journal: Analysis of Modular Hub Genes and Therapeutic Targets across Stages of Non-Small Cell Lung Cancer Transcriptome. (Pubmed Central) - Oct 26, 2024 Additional candidates like pinocembrin, which reduces NSCLC cell invasion by modulating epithelial-mesenchymal transition, and citalopram, an SSRI with anti-carcinogenic properties, were also identified. These findings provide valuable insights into the molecular underpinnings of NSCLC and suggest new directions for therapeutic strategies through drug repurposing.
- |||||||||| Journal: Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology. (Pubmed Central) - Oct 7, 2024
More importantly, we identified ten potential therapeutic agents, including ciclopirox, resveratrol, etoposide, methotrexate, trifluridine, enterolactone, troglitazone, calcitriol, dasatinib and deferoxamine, some of which have been reported to improve and treat GC and COVID-19. This research offer valuable insights into the molecular interplay between COVID-19 and GC, potentially guiding future therapeutic strategies.
- |||||||||| Journal: Novel insights into the circadian modulation of lipid metabolism in chicken livers revealed by RNA sequencing and weighted gene co-expression network analysis. (Pubmed Central) - Oct 3, 2024
Notably, we identified ten hub genes, including protein kinase C delta (PRKCD), polo like kinase 4 (PLK4), clock circadian regulator (CLOCK), steroid 5 alpha-reductase 3 (SRD5A3), BUB1 mitotic checkpoint serine/threonine kinase (BUB1B), shugoshin 1 (SGO1), NDC80 kinetochore complex component (NDC80), NIMA related kinase 2 (NEK2), minichromosome maintenance complex component 4 (MCM4), polo like kinase 1 (PLK1), potentially link circadian regulation with lipid metabolic homeostasis. These findings demonstrate the regulatory role of the circadian clock in chicken liver lipid metabolism homeostasis and provide a theoretical basis and molecular targets for optimizing the circadian clock to reduce excessive fat deposition in chickens, which is significant for the healthy development of the poultry industry.
- |||||||||| Journal: CENP-C-targeted PLK-1 regulates kinetochore function in C. elegans embryos. (Pubmed Central) - Oct 2, 2024
Disruption of the CENP-C/PLK-1 interaction leads to an imbalance in kinetochore components and a defect in chromosome congression, without affecting CDC-20 recruitment. These findings indicate that PLK-1 kinetochore recruitment by CENP-C has at least partially distinct functions than outer kinetochore PLK-1, providing a platform for a better understanding of the different roles played by PLK-1 during mitosis.
- |||||||||| volasertib (NBL-001) / Oncoheroes, Notable Labs
Journal: NOD2 reduces the chemoresistance of melanoma by inhibiting the TYMS/PLK1 signaling axis. (Pubmed Central) - Oct 2, 2024 Furthermore, we revealed that the combination of the PLK1 inhibitor volasertib (BI6727) with 5-FU or CAP had a synergistic effect repressing the proliferation, migration, and autophagy of melanoma cells. Overall, our research highlights the protective role of NOD2 in melanoma and suggests that targeting NOD2 and the TYMS/PLK1 signaling axis is a high-profile therapy that could be a prospect for melanoma treatment.
- |||||||||| Journal: Commitment to cytokinetic furrowing requires the coordinate activity of microtubules and Plk1. (Pubmed Central) - Sep 30, 2024
This phenotype is reminiscent of asymmetric furrows caused by a physical block between spindle and cortex [7-9], or by acentric spindle positioning [10-12]. The formation of these persistent "half-furrows" suggests a potential feedback mechanism between the spindle and the cortex that maintains cortical competency along the presumptive equatorial region prior to the "commitment to furrowing" stage of cytokinesis, thereby ensuring the eventual ingression of a symmetric cleavage furrow.
- |||||||||| Journal: Bioinformatics analysis: relationship between adrenocortical carcinoma and KIFs. (Pubmed Central) - Sep 21, 2024
Both KIF4A and KIF11 expression levels were marginally positively correlated with immune infiltration. Because KIF4A, KIF11, KIF20A, and KIF22 are involved in multiple ACC processes and can influence the onset and progression of ACC, they provide a mechanistically grounded framework for diagnosing and managing the disease.
- |||||||||| Journal: HN1 expression contributes to mitotic fidelity through Aurora A-PLK1-Eg5 axis. (Pubmed Central) - Sep 20, 2024
Further, the PLK1 and Aurora A kinase's phosphorylations also decreased, confirming the hypothesis that the cells struggle in mitotic progression, display nuclear and cytokinetic abnormalities with supernumerary but immature mononucleated centrosomes. In summary, we described the role of HN1 in centrosome nucleation/maturation in PLK1-Eg5 axis and concomitant mitotic spindle formation in human cells.
- |||||||||| Journal: Polo-like kinase 1 (PLK1) is a novel CARD14-binding protein in keratinocytes. (Pubmed Central) - Sep 18, 2024
Finally, disruption of the PLK1-binding motif in CARD14(E138A) increases CARD14-induced proinflammatory signaling and gene expression. Together, our data identify PLK1 as a novel CARD14-binding protein and indicate a negative regulatory role for PLK1 in CARD14 signaling.
- |||||||||| Review, Journal, BRCA Biomarker: Polo-Like Kinase 1 and DNA Damage Response. (Pubmed Central) - Sep 17, 2024
Plk1 is not only an important target of the G2/M DNA damage checkpoint but also negatively regulates the G2/M checkpoint commander Ataxia telangiectasia-mutated (ATM), promotes G2/M phase checkpoint recovery, and regulates homologous recombination repair by interacting with Rad51 and BRCA1, the key factors of homologous recombination repair. This article briefly reviews the function of Plk1 in response to DNA damage.
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