Lactate in breast cancer cells is associated with evasion of hypoxia-induced cell cycle arrest and adverse patient outcome
AbstractTumor hypoxia is a common microenvironmental factor in breast cancers, resulting in stabilization of Hypoxia-Inducible Factor 1 (HIF-1), the master regulator of hypoxic response in cells. Metabolic adaptation by HIF-1 results in inhibition of citric acid cycle, causing accumulation of lactate in large concentrations in hypoxic cancers. Lactate can therefore serve as a secondary microenvironmental factor influencing cellular response to hypoxia. Presence of lactate can alter the hypoxic response of breast cancers in many ways, sometimes in opposite manners. Lactate stabilizes HIF-1 in oxidative condition, as well as...
Source: Human Cell - March 13, 2024 Category: Cytology Source Type: research
Establishment and characterization of NCC-ASPS2-C1: a novel patient-derived cell line of alveolar soft part sarcoma
In conclusion, the establishment of NCC-ASPS2-C1 provides a valuable resource for advancing ASPS research and developing novel treatments for this challenging disease. (Source: Human Cell)
Source: Human Cell - March 13, 2024 Category: Cytology Source Type: research
Anexelekto (AXL) no more: microRNA-155 (miR-155) controls the “Uncontrolled” in SARS-CoV-2
AbstractAXL is the gene that encodes the Anexelekto (AXL) receptor tyrosine kinase that demonstrates significant roles in various cellular processes, including cell growth, survival, and migration. Anexelekto is a Greek word meaning excessive and uncontrolled, semantically implying the crucial involvement of AXL in cancer and immune biology, and in promoting cancer metastasis. AXL overexpression appears to drive epithelial to mesenchymal transition, tumor angiogenesis, decreased antitumor immune response, and resistance to therapeutic agents. Recently, AXL has been reported to play important roles in several viral infectio...
Source: Human Cell - March 12, 2024 Category: Cytology Source Type: research
Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB8-C1 and NCC-GCTB9-C1
AbstractGiant cell tumor of bone (GCTB) is a rare osteolytic bone tumor consisting of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. Although GCTB predominantly exhibits benign behavior, the tumor carries a significant risk of high local recurrence. Furthermore, GCTB can occasionally undergo malignant transformation and distal metastasis, making it potentially fatal. The standard treatment is complete surgical resection; nonetheless, an optimal treatment strategy for advanced GCTB remains unestablished, necessitating expanded preclinical research to identify appropriate therapeutic options. Howeve...
Source: Human Cell - March 11, 2024 Category: Cytology Source Type: research
Liraglutide prevents cellular senescence in human retinal endothelial cells (HRECs) mediated by SIRT1: an implication in diabetes retinopathy
AbstractDiabetes mellitus (DM) is a chronic metabolic disorder affecting millions of people worldwide, characterized by dysregulated glucose homeostasis and hyperglycemia. Diabetic retinopathy (DR) is one of the serious multisystemic complications. Aging is an important risk factor for DR. Endothelial sirtuin 1 (SIRT1) plays an important role in regulating the pathophysiology of glucose metabolism, cellular senescence, and aging. Liraglutide, an analog of Glucagon-like peptide 1 (GLP-1), has been widely used in the treatment of DM. However, the effects of Liraglutide on DR are less reported. Here, we investigated whether t...
Source: Human Cell - March 4, 2024 Category: Cytology Source Type: research
Transcription factors in chimeric antigen receptor T-cell development
AbstractChimeric antigen receptor (CAR) T-cell therapy is a new and innovative approach to treating cancers that has shown promising results in the treatment of lymphoma. However, it has been found to be less effective in the treatment of solid tumors. To overcome the limitation, researchers have explored the use of combined CAR-T therapy with other complementary regimens that target specific genes or biomarkers, which would enhance the synergistic therapeutic effects. Transcription factors (TFs) have been identified as potential markers that can regulate gene expression in CAR-T cells to enhance their cytotoxicity and saf...
Source: Human Cell - March 4, 2024 Category: Cytology Source Type: research
Tetramerization of pyruvate kinase M2 attenuates graft-versus-host disease by inhibition of Th1 and Th17 differentiation
AbstractLethal graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT). Pyruvate kinase M2 (PKM2) is essential for CD4+ T-cell differentiation. Using the well-characterized mouse models of Allo-HSCT, we explored the effects of TEPP-46-induced PKM2 tetramerization on GVHD and graft-versus-leukemia (GVL) activity. TEPP-46 administration significantly improved the survival rate of GVHD. The severity of GVHD and histopathological damage of GVHD-targeted organs were obviously alleviated by PKM2 tetramerization. Additionally, tetramerized PKM2 inhibited the act...
Source: Human Cell - February 28, 2024 Category: Cytology Source Type: research
Protein regulator of cytokinesis 1 accentuates cholangiocarcinoma progression via mTORC1-mediated glycolysis
This study aimed to investigate the expression of protein regulator of cytokinesis 1 (PRC1) in cholangiocarcinoma (CHOL) and elucidate its potential impact as well as the underlying mechanisms governing the progression of CHOL. In this study, we used CHOL cells (HUCCT1, RBE, and CCLP1) and conducted a series of experiments, including qRT-PCR, cell counting kit-8 assays, EdU assays, flow cytometry, wound healing assays, Transwell assays, western blotting, double luciferase assays, and ELISA. Subsequently, a mouse model was established using cancer cell injections. Haematoxylin –eosin staining, along with Ki67 and TUNEL as...
Source: Human Cell - February 28, 2024 Category: Cytology Source Type: research
MYCN immunohistochemistry as surrogate marker for MYCN-amplified spinal ependymomas
AbstractMYCN (master regulator of cell cycle entry and proliferative metabolism) gene amplification defines a molecular subgroup of spinal cord ependymomas that show high-grade morphology and aggressive behavior. Demonstration ofMYCN amplification by DNA methylation or fluorescence-in situ hybridization (FISH) is required for diagnosis. We aimed to (i) assess prevalence and clinicopathological features ofMYCN-amplified spinal ependymomas and (ii) evaluate utility of immunohistochemistry (IHC) for MYCN protein as a surrogate for molecular testing. A combined retrospective –prospective study spanning 8 years was designed ...
Source: Human Cell - February 27, 2024 Category: Cytology Source Type: research
Wnt, notch signaling and exercise: what are their functions?
AbstractIn the last decade, the study of Wnt and Notch signaling in cell biology has led to significant progress in understanding embryogenesis, bone development, muscle healing, neurogenesis, and tumorigenesis. It has been found that regular physical activity can counteract the decline of skeletal muscle caused by aging, which is linked to osteoporosis, regenerative neurogenesis, hippocampal function, cognitive ability, and the creation of neuromuscular junctions. Despite these discoveries, there is still uncertainty about how cell biology and exercise can impact the Wnt and Notch signaling pathways in the locomotor syste...
Source: Human Cell - February 22, 2024 Category: Cytology Source Type: research
Saracatinib prompts hemin-induced K562 erythroid differentiation but suppresses erythropoiesis of hematopoietic stem cells
AbstractHuman myeloid leukemia cells (such as K562) could be used for the study of erythropoiesis, and mature erythroid markers and globins could be induced during leukemia cell differentiation; however, the pathways involved are different compared with those of hematopoietic stem cells (HSCs).We identified the differentially expressed genes (DEGs) of K562 cells and HSCs associated with stem cells and erythroid differentiation. Furthermore, we showed that hemin-induced differentiation of K562 cells could be induced by serum starvation or treatment with the tyrosine kinase inhibitor saracatinib. However, erythroid different...
Source: Human Cell - February 22, 2024 Category: Cytology Source Type: research
Identification of a family with van der Hoeve ’s syndrome harboring a novel COL1A1 mutation and generation of patient-derived iPSC lines and CRISPR/Cas9-corrected isogenic iPSCs
In this study, we identified a novel frameshift mutation of theCOL1A1 gene (c.1607delG) in a family with OI using whole-exome sequencing, bioinformatics analysis and Sanger sequencing. This mutation may lead to the deletion of a portion of exon 23 and the generation of a premature stop codon in theCOL1A1 gene. To further investigate the impact of this mutation, we established two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells of OI patients carrying a novel mutation in theCOL1A1 gene. Osteoblasts (OB) derived from OI-iPSCs exhibited reduced production of type I collagen and diminished ab...
Source: Human Cell - February 20, 2024 Category: Cytology Source Type: research
Establishment and characterization of NCC-DFSP5-C1: a novel patient-derived dermatofibrosarcoma protuberans cell line
AbstractDermatofibrosarcoma protuberans (DFSP) is the most prevalent dermal sarcoma, characterized by the presence of the fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor beta chain (PDGFB) gene. Although PDGF receptor inhibitor imatinib mesylate was approved for the treating patients with unresectable or metastatic DFSP, disease progression was shown in 9.2% of the patients. Therefore, developing novel therapeutic strategies is crucial for improving the prognosis of DFSP. Patient-derived cell lines play a vital role in preclinical studies; however, only a limited number of DFSP c...
Source: Human Cell - February 19, 2024 Category: Cytology Source Type: research
Establishment and characterization of ZJUCHi003: an induced pluripotent stem cell line from a patient with Temple –Baraitser/Zimmermann–Laband syndrome carrying KCNH1 c.1070G & gt; A (p.R357Q) variant
This study established an induced pluripotent stem cell (iPSC) line using urinary cells from a girl withKCNH1 recurrent/hotspot pathogenic variant c.1070G > A (p.R357Q). The cell identity, pluripotency, karyotypic integrity, absence of reprogramming virus and mycoplasma contamination, and differential potential to three germ layers of the iPSC line, named as ZJUCHi003, were characterized and confirmed. Furthermore, ZJUCHi003-derived neurons manifeste d slower action potential repolarization process and wider action potential half-width than the normal neurons. This cell line will be useful for investigating the pa...
Source: Human Cell - February 19, 2024 Category: Cytology Source Type: research
Prognostic significance and immune escape implication of tumor-infiltrating neutrophil plasticity in human head and neck squamous cell carcinoma
AbstractTumor-infiltrating neutrophils play a crucial role in the progression of head and neck squamous cell carcinoma (HNSCC). Here, we aimed to statistically quantify the plasticity of HNSCC-infiltrating N2/N1 neutrophils and examine its impacts on survival and immune infiltration landscape. A retrospective study of 80 patients who underwent curative surgical resection for HNSCC between 2014 and 2017 was conducted in this study. HNSCC-infiltrating neutrophil phenotypes were classified using immunofluorescence staining, and the N2/N1 neutrophil plasticity was evaluated via the ratio of N2/N1 neutrophils. We then assessed ...
Source: Human Cell - February 15, 2024 Category: Cytology Source Type: research
