Characterizing the molecular mechanisms of acquired temozolomide resistance in the U251 glioblastoma cell line by protein microarray.

Acquired chemoresistance refers to tumor cells gradually losing their sensitivity to anticancer drugs during the course of treatment, resulting in tumor progression or recurrence. This phenomenon, which has deleterious outcomes for the patient, has long been observed in patients with glioblastoma receiving temozolomide (TMZ)-based radiochemotherapy. Currently, the mechanisms for acquired TMZ chemoresistance are not fully understood.

Toll-like receptor-4/p38 MAPK signaling in the dorsal horn contributes to P2X4 receptor activation and BDNF over-secretion in cancer induced bone pain.

Our previous research suggested that the P2X4 receptor (P2X4R) expression in microglia was involved in the activation of toll-like receptor-4 (TLR4) in the dorsal horn in the rat model of cancer induced bone pain (CIBP). In this study, we focused on whether TLR4- mitogen-activated protein kinases, p38 (p38 MAPK) contributes to P2X4R activation and brain-derived neurotrophic factor (BDNF) over-secretion in CIBP. In in vitro experiment, the results showed that BDNF expression evoked by ATP stimulation was dependent on TLR4-p38.

AKT2-knockdown suppressed viability with enhanced apoptosis, and attenuated chemoresistance to temozolomide of human glioblastoma cells in vitro and in vivo.

The AKT2 kinase (protein kinase Bβ) is overexpressed in high-grade gliomas. Upregulation of the AKT2 gene has been previously observed in glioblastoma patients suffering from chemotherapy failure and tumor progress. In this study, we aimed to evaluate the effect of AKT2 on viability and chemoresistance in the human glioblastoma cell line U251.

MCP-1 stimulates spinal microglia via PI3K/Akt pathway in bone cancer pain.

Accumulating evidence suggests that chemokine monocyte chemoattractant protein-1 (MCP-1) is significantly involved in the activation of spinal microglia associated with pathological pain, at the same time that the phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) pathway localized in spinal microglia is involved in both neuropathic and inflammatory pain. However, whether there is a connection between MCP-1 and the PI3K/Akt pathway and in their underlying mechanisms in bone cancer pain (BCP) has not yet been elucidated. In the current study, we investigated the expression changes of p-Akt in microglia and OX-42 (microglia marker) after being stimulated with MCP-1 in vitro, as well as in a BCP model that was established by an intramedullary injection of mammary gland carcinoma cells(Walker 256 cells) into the tibia of rats.

P2X4 receptor in the dorsal horn partially contributes to brain-derived neurotrophic factor oversecretion and toll-like receptor-4 receptor activation associated with bone cancer pain.

Previous studies have suggested that the microglial P2X7 purinoceptor is involved in the release of tumor necrosis factor-α (TNFα) following activation of toll-like receptor-4 (TLR4), which is associated with nociceptive behavior. In addition, this progress is evoked by the activation of the P2X4 purinoceptor (P2X4R). Although P2X4R is also localized within spinal microglia in the dorsal horn, little is known about its role in cancer-induced bone pain (CIBP), which is in some ways unique.

Expression of R132H mutational IDH1 in human U87 glioblastoma cells affects the SREBP1a pathway and induces cellular proliferation.

Sterol regulatory element-binding protein-1a (SREBP1a) is a member of the SREBP family of transcription factors, which mainly controls homeostasis of lipids. SREBP1a can also activate the transcription of isocitrate dehydrogenase 1 (IDH1) by binding to its promoter region. IDH1 mutations, especially R132H mutation of IDH1, are a common feature of a major subset of human gliomas.

Activation of spinal TDAG8 and its downstream PKA signaling pathway contribute to bone cancer pain in rats.

Bone cancer pain is difficult to treat and has a strong impact on the quality of life of patients. Few therapies have emerged because the molecular mechanisms underlying bone cancer pain are poorly understood. Recently, T-cell death-associated gene 8 (TDAG8) has been shown to participate in complete Freund's adjuvant-induced chronic inflammatory pain.

Brain-derived neurotrophic factor modulates N-methyl-D-aspartate receptor activation in a rat model of cancer-induced bone pain.

Brain-derived neurotrophic factor (BDNF) released within the spinal cord induces phosphorylation of N-methyl-D-aspartate (NMDA) receptors on the spinal cord neurons. This process is necessary for maintaining pain hypersensitivity after nerve injury. However, little is known about the role of BDNF and NMDA receptors in cancer-induced bone pain (CIBP), whose features are unique.

Preparation, characterization, and assessment of the antiglioma effects of liposomal celastrol.

The role of celastrol in the treatment of cancer has been an area of growing interest. To circumvent the issues of low solubility, poor bioavailability, and systemic toxicity of celastrol, we prepared liposomal celastrol using the thin-film dispersion method. We characterized particle size, encapsulation efficiency, and pharmacological parameters of liposomal celastrol.

Minocycline-induced reduction of brain-derived neurotrophic factor expression in relation to cancer-induced bone pain in rats.

Previous studies have suggested that the release of brain-derived neurotrophic factor (BDNF) from microglia in spinal cord is necessary for maintaining pain hypersensitivity after nerve injury. However, little is known about its role in cancer-induced bone pain (CIBP), which is in some ways unique. This study demonstrates a critical role of minocycline (a potent inhibitor of microglial activation)-modulated BDNF in the induction and maintenance of behavioral hypersensitivity in a rat model of CIBP.

[The role of brain-derived neurotrophic factor in pain facilitation and spinal mechanism in rat model of bone cancer pain].

Objective: To investigate the role of brain-derived neurotrophic factor (BDNF) in pain facilitation and spinal mechanisms in the rat model of bone cancer pain.

Methods: The bone cancer pain model was developed by inoculated Walker 256 mammary gland carcinoma cells into the tibia medullary cavity. Sixty SD female rats were divided into 5 groups (n = 12 each) randomly; group I: control group (sham operation); group II: model group; group III: control group + anti-BDNF intrathecal (i.

Cancer-induced bone pain sequentially activates the ERK/MAPK pathway in different cell types in the rat spinal cord.

Background: Previous studies have demonstrates that, after nerve injury, extracellular signal-regulated protein kinase (ERK) activation in the spinal cord-initially in neurons, then microglia, and finally astrocytes. In addition, phosphorylation of ERK (p-ERK) contributes to nociceptive responses following inflammation and/or nerve injury. However, the role of spinal cells and the ERK/MAPK pathway in cancer-induced bone pain (CIBP) remains poorly understood.

Isocitrate dehydrogenase mutations may be a protective mechanism in glioma patients.

Gliomas are the most common human brain tumours and can be classified into four grades based on clinical and pathological criteria. A recent cancer genome-sequencing project revealed that more than 70% of low-grade gliomas bear mutations in one of two NAD(+)-dependent isocitrate dehydrogenase enzymes, namely, IDH1 and IDH2. Based on the findings that glioma-derived mutations in IDH1 can inhibit the catalytic activity of the enzyme, induce HIF-1α, and can produce 2-hydroxyglutarate, two research groups speculated that the IDH mutations may contribute to the promotion of tumorigenesis in gliomas.

CD40 is a regulator for vascular endothelial growth factor in the tumor microenvironment of glioma.

CD40 is expressed in many tumor cells, however, its role in tumor biology is yet to be demonstrated. In the present study, we investigated the role of CD40 in gliomas. In vivo, we evaluated CD40 expression in 95 glioma tissues and 10 non-tumorous brain tissues and investigated the relationship between histopathological parameters, vascular density, and vascular endothelial growth factor (VEGF) expressions.

Prourokinase mutant that induces highly effective clot lysis without interfering with hemostasis.

Prourokinase (proUK) is a zymogenic plasminogen activator that at pharmacological doses is prone to nonspecific activation to urokinase. This has handicapped therapeutic exploitation of its fibrin-specific physiological properties. To attenuate this susceptibility without compromising specific activation of proUK on a fibrin clot, a Lys300-->His mutation (M5) was developed.