Artificial intelligence-based analysis of time-lapse images of sphere formation and process of plate adhesion and spread of pancreatic cancer cells.

Most pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). Spherical morphology formed in three-dimensional (3D) cultures and the effects of anticancer drugs differ between epithelial and mesenchymal PDAC cell lines. In the human pancreas, cancer cells form 3D tumors, migrate to adjacent tissues, and metastasize to other organs.

Accelerated telomere shortening in adrenal zona reticularis in patients with prolonged critical illness.

Background: The number of patients with prolonged critical illness (PCI) has been increasing in many countries, and the adrenal gland plays an important role in maintaining homeostasis during PCI. Chronic disease burden is reportedly associated with shorter telomere lengths in human tissues. Telomere shortening in human somatic cells is largely dependent on cell divisions, and critically short telomeres lead to cellular dysfunction and aging.

Multiple cystic sphere formation from PK-8 cells in three-dimensional culture.

Three-dimensional (3D) culture of cancer cells mimics the environment. Recently, we reported that pancreatic ductal adenocarcinoma (PDAC) cell lines with epithelial and mesenchymal features formed differently shaped spheres in 3D culture. However, only PK-8 cells, the epithelial PDAC cell line with the highest expression among the eight PDAC cell lines, formed multiple cystic spheres in 3D culture.

Epithelial and Mesenchymal Features of Pancreatic Ductal Adenocarcinoma Cell Lines in Two- and Three-Dimensional Cultures.

Pancreatic ductal adenocarcinoma (PDAC) is an intractable cancer that is difficult to diagnose early, and there is no cure other than surgery. PDAC is classified as an adenocarcinoma that has limited effective anticancer drug and molecular-targeted therapies compared to adenocarcinoma found in other organs. A large number of cancer cell lines have been established from patients with PDAC that have different genetic abnormalities, including four driver genes; however, little is known about the differences in biological behaviors among these cell lines.

Gp130-Mediated STAT3 Activation Contributes to the Aggressiveness of Pancreatic Cancer through Long Non-Coding RNA Expression.

Signaling pathways involving signal transducer and activator of transcription 3 (STAT3) play key roles in the aggressiveness of pancreatic ductal adenocarcinoma (PDAC), including their tumorigenesis, invasion, and metastasis. Cancer stem cells (CSCs) have been correlated with PDAC aggressiveness, and activation of STAT3 is involved in the regulation of CSC properties. Here, we investigated the involvement of interleukin-6 (IL-6) or the leukemia inhibitory factor (LIF)/glycoprotein 130 (gp130)/STAT3 pathway and their role in pancreatic CSCs.

Morphofunctional analysis of human pancreatic cancer cell lines in 2- and 3-dimensional cultures.

Genetic, transcriptional, and morphological differences have been reported in pancreatic ductal adenocarcinoma (PDAC) cases. We recently found that epithelial or mesenchymal features were enhanced in three-dimensional (3D) cultures compared to two-dimensional (2D) cultures. In this study, we examined the differences in the morphological and functional characteristics of eight PDAC cell lines in 2D and 3D cultures.

Polyvinyl alcohol increased growth, migration, invasion, and sphere size in the PK-8 pancreatic ductal adenocarcinoma cell line.

Polyvinyl alcohol (PVA) is a water-soluble synthetic polymer used in eye drops, embolization particles, and artificial cartilage. It has also been shown to cause expansion of functional multipotent self-renewing hematopoietic stem cells under serum-free conditions. In this study, we examined the effects of PVA on human pancreatic ductal adenocarcinoma (PDAC) cell lines using 2-dimensional (2D) and 3D-cultures with serum-free medium.

FGFR4 Inhibitor BLU9931 Attenuates Pancreatic Cancer Cell Proliferation and Invasion While Inducing Senescence: Evidence for Senolytic Therapy Potential in Pancreatic Cancer.

Fibroblast growth factor receptor 4 (FGFR4), one of four tyrosine kinase receptors for FGFs, is involved in diverse cellular processes. Activation of FGF19/FGFR4 signaling is closely associated with cancer development and progression. In this study, we examined the expression and roles of FGF19/FGFR4 signaling in human pancreatic ductal adenocarcinoma (PDAC).

Ganglioside GM2, highly expressed in the MIA PaCa-2 pancreatic ductal adenocarcinoma cell line, is correlated with growth, invasion, and advanced stage.

Gangliosides, a group of glycosphingolipids, are known to be cell surface markers and functional factors in several cancers. However, the association between gangliosides and pancreatic ductal adenocarcinoma (PDAC) has not been well elucidated. In this study, we examined the expression and roles of ganglioside GM2 in PDAC.

Characterization of the metastatic potential of the floating cell component of MIA PaCa-2, a human pancreatic cancer cell line.

In pancreatic cancer, morphologically and functionally heterogeneous cancer cells reside within the same patient. The heterogeneity is believed to promote metastasis and resistance to chemoradiotherapy. MIA PaCa-2, an established human pancreatic ductal adenocarcinoma (PDAC) cell line, contains round and spindle-shaped adherent cells, as well as, round floating cells.

Correlation Between Telomere Attrition of Zona Fasciculata and Adrenal Weight Reduction in Older Men.

Context: Although numerous theories are reported on sex differences in longevity, the underlying biological mechanisms remain unknown. We previously reported that telomere length in the zona reticularis cells of the human adrenal cortex was significantly longer in older than that in younger subjects. However, we could not evaluate sex differences in the telomere lengths.

Enhanced morphological and functional differences of pancreatic cancer with epithelial or mesenchymal characteristics in 3D culture.

Pancreatic cancer, composed of heterogeneous cancer cells, alters epithelial to mesenchymal features during growth and metastasis. In this study, we aimed to characterize pancreatic ductal adenocarcinoma (PDAC) cells showing epithelial or mesenchymal features in 3D culture. In 3D culture, PK-1 cells had high E-cadherin and low vimentin expression and exhibited a round-like appearance encircled by flat cells.

Fetal bovine serum enlarges the size of human pancreatic cancer spheres accompanied by an increase in the expression of cancer stem cell markers.

Pancreatic ductal adenocarcinoma (PDAC) is a major histological type of pancreatic cancer and remains one of the most lethal cancers with a high mortality rate owing to its aggressive growth, high metastatic rate, and recurrence. Recent studies on cancer stem cells (CSCs) have suggested that the aggressive growth, high metastatic rate, and recurrence might be caused by the ability of CSCs to self-renew, differentiate, and drive tumorigenesis. Thus, CSCs are expected to be a therapeutic target for PDAC.

Comparison of functional glycans between cancer stem cells and normal stem cells.

Cancer stem cells (CSCs) are a small group of cells within a tumor that preserve stemness and enhance regrowth of cancer cells. CSCs have important implications in resistance to conventional therapies and tumor relapse, although their detailed properties remain unknown. Thus, CSCs represent promising targets to improve cancer treatment.

Up-regulation of NSP3 by Oligomeric Aβ Accelerates Neuronal Death Through Cas-independent Rap1A Activation.

β-Amyloid (Aβ) plays an important role in the early pathogenesis of Alzheimer's disease (AD). In vitro studies have demonstrated that Aβ oligomers induce hippocampal and neocortical neuronal death. However the neurotoxic mechanisms by which soluble Aβ oligomers cause neuronal damage and death remain to be fully elucidated.

The role of calsyntenin-3 in dystrophic neurite formation in Alzheimer's disease brain.

β-Amyloid (Aβ) oligomers may play an important role in the early pathogenesis of Alzheimer's disease: cognitive impairment caused by synaptic dysfunction. Dystrophic neurites surrounding Aβ plaques, another pathological feature of Alzheimer's disease, are plaque-associated neuritic alterations preceding the appearance of synaptic loss. In the present review, we focus on the mechanism of dystrophic neurite formation by Aß oligomers, and discuss the neurotoxic role of Aβ-induced calsyntenin-3 in mediating dystrophic neurite formation.

Kinesin light chain-1 isoform E does not interact with calsyntenin-1.

β-Amyloid is generated by the sequential cleavage of amyloid precursor protein. Calsyntenin-1 and kinesin light chain-1 splice variant E (KLC1-E) have been proposed to regulate β-amyloid production from amyloid precursor protein. Vesicles containing calsyntenin-1 are transported from the Golgi apparatus to axons by interaction between calsyntenin-1 and KLC1 in their C-terminal regions.

Calsyntenin-3 C-terminal fragment accumulates in dystrophic neurites surrounding aβ plaques in tg2576 mouse and Alzheimer disease brains: its neurotoxic role in mediating dystrophic neurite formation.

Dystrophic neurites surrounding β-amyloid (Aβ) plaques precede neuronal death in Alzheimer disease. These neuritic alterations may be one of the initial stages for synaptic loss and dysfunction. However, intracellular pathways that cause local disruption of neuronal processes by Aβ remain to be fully elucidated.

MAP1B 1-126 interacts with tubulin isoforms and induces neurite outgrowth and neuronal death of cultured cortical neurons.

Previously we reported that overexpression of MAP1B containing N-terminal 126 amino acids promoted neuronal death. Here, we identified α-, β-, and βIII-tubulins as proteins interacting with MAP1B 1-126 by two-hybrid and pull-down assays. Transfection experiments indicated that MAP1B 1-126 interacts with microtubules, but to a much lesser extent than two previously reported microtubule-binding domains.

Up-regulation of calsyntenin-3 by β-amyloid increases vulnerability of cortical neurons.

β-Amyloid (Aβ) may play an important role in the pathogenesis of Alzheimer's disease. However, a causal relationship between Aβ oligomers and layer-specific neurodegeneration has not been clarified. Here we show up-regulation of calsyntenin (Cst)-3 in cultured neurons treated with Aβ oligomers and in Tg2576 mice.

Differential regulation of basic helix-loop-helix factors Mash1 and Olig2 by beta-amyloid accelerates both differentiation and death of cultured neural stem/progenitor cells.

Despite increased neurogenic differentiation markers in the hippocampal CA1 in Alzheimer disease, neurons are not replaced in CA1 and the neocortex in the disease. beta-Amyloid (Abeta) might cause deterioration of the brain microenvironment supporting neurogenesis and the survival of immature neurons. To test this possibility, we examined whether Abeta alters the expression of cell fate determinants in cerebral cortical cultures and in an Alzheimer disease mouse model (PrP-APP(SW)).

Tolerance of aged rat brains to mild hyperoxia: possible involvement of higher GIF content.

We investigate the aging effects of the hyperoxia-mediated induction of two antioxidants and three antioxidant enzymes in the rat brain. All of these genes responded to hyperoxia in young but not aged brains. Despite the partial inactivation of CuZn SOD and glutathione peroxidase by hyperoxia in aged rat brains, lipid peroxidation did not increase.

Effects of 60% oxygen inhalation on the survival and antioxidant enzyme activities of young and old rats.

Under 60% oxygen, both the 50% and maximum survival times of old rats were markedly shortened, and the maximum survival time of young rats did not change although the 50% survival time was shortened. In addition, the mean body weight of the old rats decreased rapidly, while that of the young rats increased very slowly after the small decrease. In lungs of the young and old rats, the activities of catalase and Mn superoxide dismutase (SOD) were increased, while those of CuZn SOD and glutathione peroxidase remained unchanged.

Growth inhibitory factor prevents neurite extension and the death of cortical neurons caused by high oxygen exposure through hydroxyl radical scavenging.

Growth inhibitory factor (GIF), a brain-specific member of the metallothionein family (MT-III), has been characterized as a inhibitory substance for neurotrophic factors in Alzheimer's disease brains. However, the function of GIF, other than the inhibition of neurotrophic factors, remains unknown. We demonstrate here that exogenous GIF prevents neurite extension of cortical neurons in the early period of differentiation and the death of differentiated neurons caused by high oxygen exposure.