Dickkopf 4 Alone and in Combination with Leucyl-tRNA Synthetase as a Good Prognostic Biomarker for Human Colorectal Cancer.

The prognosis of patients with colorectal cancer (CRC) is affected by invasion and metastasis. Leucyl-tRNA synthetase (LARS) was shown to be related to the growth and migration of lung cancer cells. Dickkopf 4 (DKK4) is known as a Wnt/-catenin pathway inhibitor, and its upregulation was reported in several cancers.

COUP-TFII plays a role in cAMP-induced Schwann cell differentiation and in vitro myelination by up-regulating Krox20.

Schwann cells (SCs) are known to produce myelin for saltatory nerve conduction in the peripheral nervous system (PNS). Schwann cell differentiation and myelination processes are controlled by several transcription factors including Sox10, Oct6/Pou3f1, and Krox20/Egr2. Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII/NR2F2) is an orphan receptor that plays a role in the development and differentiation.

PGC-1α Regulates Cell Proliferation, Migration, and Invasion by Modulating Leucyl-tRNA Synthetase 1 Expression in Human Colorectal Cancer Cells.

Although mounting evidence has demonstrated that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) can promote tumorigenesis, its role in cancer remains controversial. To find potential target molecules of PGC-1α, GeneFishing DEG (differentially expressed genes) screening was performed using stable HEK293 cell lines expressing PGC-1α (PGC-1α-HEK293). As results, leucyl-tRNA synthetase 1 (LARS1) was upregulated.

Doxycycline potentiates the anti-proliferation effects of gemcitabine in pancreatic cancer cells.

Gemcitabine is often recommended as a first-line treatment for patients with metastatic pancreatic cancer. However, gemcitabine resistance is a major challenge in the treatment of pancreatic ductal adenocarcinoma. Our group serendipitously identified the role of doxycycline as a potentiator of gemcitabine efficacy in pancreatic cancer cells.

Recent progress on the role and molecular mechanism of chicken ovalbumin upstream promoter-transcription factor II in cancer.

Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is an orphan receptor that regulates the expression of genes involved in development and homeostasis. COUP-TFII is also dysregulated in cancer, where it plays important roles in oncogenesis and malignant progression. Recent studies have also investigated altered microRNA-mediated regulation of COUP-TFII in cancer.

COUP-TFII Overexpression Inhibits Cell Proliferation and Invasion Increased Expression of p53 and PTEN and Decreased Akt Phosphorylation in Human Colorectal Cancer SNU-C4 Cells.

Background/aim: Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) plays an important role in cancer. We examined the effect of COUP-TFII overexpression on the proliferation and invasion of the human colorectal cancer SNU-C4 cells.

Materials And Methods: SNU-C4 cells were stably transfected with COUP-TFII expression plasmid to overexpress COUP-TFII (COUP-TFII-SNU-C4 cells).

PGC-1α Regulates Cell Proliferation and Invasion AKT/GSK-3β/β-catenin Pathway in Human Colorectal Cancer SW620 and SW480 Cells.

Background/aim: Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a master regulator of mitochondrial biogenesis and metabolism. We investigated the effect of PGC-1α knockdown in the human colorectal cancer cell line SW620, which highly expresses PGC-1α.

Materials And Methods: We established the PGC-1α shRNA-silenced SW620 stable cell line (PGC-1α shRNA-SW620 cells) and examined cell proliferation by cell counts and carboxyfluorescein succinimidyl ester (CFSE) staining, migration by wound-healing and transwell migration assay, and invasion by transwell assays.

p53 regulates mitochondrial dynamics by inhibiting Drp1 translocation into mitochondria during cellular senescence.

Cellular senescence acts as an important barrier to tumorigenesis by eliminating precancerous cells. Previous studies have shown an essential role of the tumor suppressor p53 in cellular senescence, but how p53 induces cellular senescence is not fully understood. We found that p53 promoted the formation of highly interconnected and elongated mitochondria prior to the onset of cellular senescence.

Evaluation of neutrophil extracellular traps as the circulating marker for patients with acute coronary syndrome and acute ischemic stroke.

Introduction: Neutrophil extracellular traps (NETs) are known to be induced by various factors. In this study, we tried to identify circulating levels of NETs in patients with acute coronary syndrome (ACS) and acute ischemic stroke (AIS) and to confirm its suitability as a new circulating marker in their detection.

Methods: We prospectively enrolled 95 patients with a diagnosis of ACS (N = 37) or AIS (N = 58) in Dong-A University Hospital, Busan, Korea.

COUP-TFII Knock-down Promotes Proliferation and Invasion in Colorectal Cancer Cells Activation of Akt Pathway and Up-regulation of FOXC1.

Background/aim: The chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) regulates cancer cell proliferation and invasion via complex molecular mechanisms. We aimed to investigate whether COUP-TFII modulates proliferation and invasion of the colorectal adenocarcinoma cell line HT-29.

Materials And Methods: HT-29 cells were stably tranfected with COUP-TFII shRNA plasmid to knock-down COUP-TFII (COUP-TFII shRNA-HT-29 cells).

Heat Shock Protein 90 is Required for cAMP-Induced Differentiation in Rat Primary Schwann Cells.

Schwann cells (SCs) play an important role in producing myelin for rapid neurotransmission in the peripheral nervous system. Activation of the differentiation and myelination processes in SCs requires the expression of a series of transcriptional factors including Sox10, Oct6/Pou3f1, and Egr2/Krox20. However, functional interactions among several transcription factors are poorly defined and the important components of the regulatory network are still unknown.

Holotoxin A₁ Induces Apoptosis by Activating Acid Sphingomyelinase and Neutral Sphingomyelinase in K562 and Human Primary Leukemia Cells.

Marine triterpene glycosides are attractive candidates for the development of anticancer agents. Holotoxin A₁ is a triterpene glycoside found in the edible sea cucumber, We previously showed that cladoloside C₂, the 25(26)-dihydro derivative of holotoxin A₁ induced apoptosis in human leukemia cells by activating ceramide synthase 6. Thus, we hypothesized that holotoxin A₁, which is structurally similar to cladoloside C₂, might induce apoptosis in human leukemia cells through the same molecular mechanism.

Peroxisome Proliferator-Activated Receptor and PGC-1 in Cancer: Dual Actions as Tumor Promoter and Suppressor.

Peroxisome proliferator-activated receptor (PPAR) is part of a nuclear receptor superfamily that regulates gene expression involved in cell differentiation, proliferation, immune/inflammation response, and lipid metabolism. PPAR coactivator-1 (PGC-1), initially identified as a PPAR-interacting protein, is an important regulator of diverse metabolic pathways, such as oxidative metabolism and energy homeostasis. The role of PGC-1 in diabetes, neurodegeneration, and cardiovascular disease is particularly well known.

Peroxisome proliferator-activated receptor γ coactivator-1α is a predictor of lymph node metastasis and poor prognosis in human colorectal cancer.

Peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ coactivator-1α (PGC-1α) expression levels are correlated with clinical outcome in breast cancer. However, the potential biological and clinical significance of PPARγ and PGC-1α in colorectal cancer remains unknown. Here we investigated PPARγ and PGC-1α expression in colorectal cancer, and the associations of these expression levels with clinicopathological features.

and anti-leukemic effects of cladoloside C are mediated by activation of Fas/ceramide synthase 6/p38 kinase/c-Jun NH-terminal kinase/caspase-8.

We previously demonstrated that the quinovose-containing hexaoside stichoposide C (STC) is a more potent anti-leukemic agent than the glucose-containing stichoposide D (STD), and that these substances have different molecular mechanisms of action. In the present study, we investigated the novel marine triterpene glycoside cladoloside C from , which has the same carbohydrate moiety as STC. We assessed whether cladoloside C could induce apoptosis in K562 and HL-60 cells.

Expression of fatty acid synthase is regulated by PGC‑1α and contributes to increased cell proliferation.

We previously demonstrated that overexpression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) promotes increased cell proliferation and tumorigenic potential through upregulation of specificity protein 1 (Sp1) and acyl-CoA-binding protein (ACBP). Fatty acid synthase (FASN) is a key enzyme in fatty acid biosynthesis, and its expression in various cancers is associated with survival, poor prognosis and cancer recurrence. In the present study, we evaluated whether PGC-1α regulated FASN expression in human colorectal cancer (SNU-C4 and HT-29) cells.

Expression of chicken ovalbumin upstream promoter-transcription factor II and liver X receptor as prognostic indicators for human colorectal cancer.

Cholesterol increases the risk of colorectal cancer. Liver X receptor (LXR), retinoid X receptor (RXR)α and sterol regulatory element binding protein (SREBP)-1c are transcriptional regulators of lipid metabolism. Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) serves an essential role in angiogenesis and development, but its role in cancer is controversial.

Schwann cell dedifferentiation-associated demyelination leads to exocytotic myelin clearance in inflammatory segmental demyelination.

Schwann cells (SCs), which form the peripheral myelin sheath, have the unique ability to dedifferentiate and to destroy the myelin sheath under various demyelination conditions. During SC dedifferentiation-associated demyelination (SAD) in Wallerian degeneration (WD) after axonal injury, SCs exhibit myelin and junctional instability, down-regulation of myelin gene expression and autophagic myelin breakdown. However, in inflammatory demyelinating neuropathy (IDN), it is still unclear how SCs react and contribute to segmental demyelination before myelin scavengers, macrophages, are activated for phagocytotic myelin digestion.

Cooperative interaction of hepatocyte growth factor and neuregulin regulates Schwann cell migration and proliferation through Grb2-associated binder-2 in peripheral nerve repair.

The sequential reactive changes in Schwann cell phenotypes in transected peripheral nerves, including dedifferentiation, proliferation and migration, are essential for nerve repair. Even though the injury-induced migratory and proliferative behaviors of Schwann cells resemble epithelial and mesenchymal transition (EMT) in tumors, the molecular mechanisms underlying this phenotypic change of Schwann cells are still unclear. Here we show that the reactive Schwann cells exhibit migratory features dependent on the expression of a scaffolding oncoprotein Grb2-associated binder-2 (Gab2), which was transcriptionally induced by neuregulin 1-ErbB2 signaling following nerve injury.

Ceramide as a Target of Marine Triterpene Glycosides for Treatment of Human Myeloid Leukemia.

Acute myeloid leukemia (AML) is a heterogeneous myeloid clonal disorder exhibiting the accumulation of immature myeloid progenitors in the bone marrow and peripheral blood. Standard AML therapy requires intensive combination chemotherapy, which leads to significant treatment-related toxicity. The search for new, low toxic marine agents, inducing the generation of ceramide in leukemic cells is a new approach to improve the therapy of leukemia.

Platelet Activation: The Mechanisms and Potential Biomarkers.

Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, mediating inflammatory and immunomodulatory activities. Our knowledge about how platelets modulate inflammatory and immunity has greatly improved in recent years. In this review, we discuss recent advances in the pathways of platelet activation and potential application of platelet activation biomarkers to diagnosis and prediction of disease states.

By activating Fas/ceramide synthase 6/p38 kinase in lipid rafts, stichoposide D inhibits growth of leukemia xenografts.

Stichoposide D (STD) is a marine triterpene glycoside isolated from sea cucumbers. We examined the molecular mechanisms underlying the antitumor activity of STD in human leukemia cells. The role of Fas (CD95), ceramide synthase 6 (CerS6) and p38 kinase during STD-induced apoptosis was examined in human leukemia cells.

Overexpression of PGC‑1α enhances cell proliferation and tumorigenesis of HEK293 cells through the upregulation of Sp1 and Acyl-CoA binding protein.

Peroxisome proliferator-activated receptor γ coactivator-1α (PGC‑1α), a coactivator interacting with multiple transcription factors, regulates several metabolic processes. Although recent studies have focused on the role of PGC‑1α in cancer, the underlying molecular mechanism has not been clarified. Therefore, we evaluated the role of PGC‑1α in cell proliferation and tumorigenesis using human embryonic kidney (HEK)293 cells and colorectal cancer cells.

Relationships between chemical structures and functions of triterpene glycosides isolated from sea cucumbers.

Many marine triterpene glycosides have in vitro and in vivo activities with very low toxicity, suggesting that they are suitable agents for the prevention and treatment of different diseases, particularly cancer. However, the molecular mechanisms of action of natural marine compounds in cancer, immune, and other various cells are not fully known. This review focuses on the structural characteristics of marine triterpene glycosides and how these affect their biological activities and molecular mechanisms.

Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma.

Aims: Although earlier reports highlighted a tumor suppressor role for manganese superoxide dismutase (MnSOD), recent evidence indicates increased expression in a variety of human cancers including aggressive breast carcinoma. In the present article, we hypothesized that MnSOD expression is significantly amplified in the aggressive breast carcinoma basal subtype, and targeting MnSOD could be an attractive strategy for enhancing chemosensitivity of this highly aggressive breast cancer subtype.

Results: Using MDA-MB-231 and BT549 as a model of basal breast cancer cell lines, we show that knockdown of MnSOD decreased the colony-forming ability and sensitized the cells to drug-induced cell death, while drug resistance was associated with increased MnSOD expression.