GNAO1: A Novel Tumor Suppressor Gene in Colorectal Cancer Pathogenesis.

Background/aim: This study examined the role of GNAO1 as a potential tumor suppressor gene in colorectal cancer (CRC).

Materials And Methods: RNA-seq data analysis revealed a significant GNAO1 down-regulation in colon cancer tissues compared to normal colon tissues.

Results: GNAO1 over-expression in CRC cell lines inhibited cell proliferation, migration, and tumor formation both in vitro and in vivo.

Upregulation of microRNA-597 in myelodysplastic syndromes induces apoptosis through FOSL2 inhibition.

Introduction: Dysregulation of microRNAs (miRNAs) has been associated with the pathophysiology of myelodysplastic syndrome (MDS). Trisomy 8 is the most frequent chromosomal abnormalities in Korean patients with MDS. We investigated the dysregulation of miR-597-5p, located on chromosome 8, which is reported to induce cell death in numerous cancers.

HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells.

The Hsp70-binding protein 1 (HspBP1) belongs to a family of co-chaperones that regulate Hsp70 activity and whose biological significance is not well understood. In the present study, we show that when HspBP1 is either knocked down or overexpressed in BRCA1-proficient breast cancer cells, there were profound changes in tumorigenesis, including anchorage-independent cell growth in vitro and in tumor formation in xenograft models. However, HspBP1 did not affect tumorigenic properties in BRCA1-deficient breast cancer cells.

Jagged-1 Expression Level Is Correlated With Recurrence of Stage III Colorectal Cancer in Patients Receiving Adjuvant Chemotherapy.

Background/aim: Previous reports have indicated that increased expression of Jagged-1 (JAG1) may predict chemotherapy response and poor prognosis for patients with recurrent or metastatic colorectal cancer (CRC). This study aimed to investigate the clinical impact of JAG1 expression level in patients with CRC, including recurrence, especially in those diagnosed with lymph node-positive stage III CRC who underwent complete resection and appropriate adjuvant chemotherapy.

Patients And Methods: All patients were enrolled through a retrospective chart review, and only those for whom the clinical course and all clinical information were adequately determined according to the inclusion criteria were selected for retrospective review through medical records.

Extremely rare case of successful treatment of metastatic ovarian undifferentiated carcinoma with high-dose combination cytotoxic chemotherapy: A case report.

Background: Ovarian undifferentiated carcinomas are significantly rare and have an aggressive clinical course. Surgical resection is the only curative treatment in early-stage ovarian undifferentiated carcinomas that has a favorable prognosis. In case of recurrent and metastatic disease, palliative chemotherapy is the only available treatment.

Clinical Significance of Jagged-1 Activated by APEX1 as a Chemoresistance Factor in Advanced Gastric Cancer.

Background/aim: We investigated the clinical role of the molecular targets, APEX1 and Jagged-1, and the Apex1 - Jagged-1 cascade in gastric cancer cells.

Materials And Methods: We used 6 human gastric cancer cell lines (SNU-1, SNU-5, SNU-16, NCI-N87, KATO- III and AGS), and demonstrated the chemosensitivity of APEX1 and Jagged-1 through the MTT assay and immunoblotting. Tumor growth was assayed following cisplatin and 5-FU treatment using a xenograft model injected with KATO-III cells.

Isolated peritoneal lymphomatosis defined as post-transplant lymphoproliferative disorder after a liver transplant: A case report.

Background: Post-transplant lymphoproliferative disorder (PTLD) is a fatal complication of solid organ transplantation or allogenic hematopoietic stem cell transplantation that is associated with immunosuppressive therapy. Potential manifestations are diverse, ranging from reactive lymphoid hyperplasia to high-grade lymphoma. PTLD is usually of B-cell origin and associated with Epstein-Barr virus (EBV) infection.

Evaluation and Clinical Significance of Jagged-1-activated Notch Signaling by APEX1 in Colorectal Cancer.

Background/aim: Colorectal cancer (CRC) is one of the most common in the world and its prevalence is rapidly increasing. Jagged-1-activated Notch signaling by apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) promotes CRC, and high expression of Jagged-1 is associated with poor prognosis. However, its clinical implication is unknown.

Bronchobiliary fistula after ramucirumab treatment for advanced gastric cancer: A case report.

Background: Bronchobiliary fistula (BBF) is a rare disease characterized by an abnormal connection between the biliary system and bronchi. Traditional causes of BBF include trauma and infections, and more recent causes include malignancies and certain cancer treatments. Ramucirumab is an antivascular endothelial growth factor receptor 2 monoclonal antibody, currently used as a second-line treatment for gastric cancer.

Arterioportal shunt incidental to treatment with oxaliplatin that mimics recurrent gastric cancer.

Arterioportal shunt (APS) is an organic communication between the hepatic arterial system and the portal venous system. The APS is one of the major causes of transient hepatic attenuation differences on dynamic computed tomography (CT) or magnetic resonance imaging (MRI). This condition is usually associated with trauma, liver cirrhosis, and malignancies of the liver.

Evaluation of the prevalence and clinical impact of toxocariasis in patients with eosinophilia of unknown origin.

Background/aims: Eosinophilia has numerous diverse causes, and in many patients, it is not possible to establish the cause of eosinophilia. Recently, toxocariasis was introduced as one cause of eosinophilia. The aims of this study were to evaluate the prevalence of toxocariasis and the clinical impact of albendazole treatment for toxocariasis in patients suspected of eosinophilia of unknown origin.

53BP1 contributes to regulation of autophagic clearance of mitochondria.

Autophagy, the primary recycling pathway within cells, plays a critical role in mitochondrial quality control under normal growth conditions and in the cellular response to stress. Here we provide evidence that 53BP1, a DNA damage response protein, is involved in regulating mitochondrial clearance from the cell via a type of autophagy termed mitophagy. We found that when either human or mouse cells were 53BP1-deficient, there was an increase in mitochondrial abnormalities, as observed through staining intensity, aggregation, and increased mass.

The oncogenic effects of p53-inducible gene 3 (PIG3) in colon cancer cells.

The p53-inducible gene 3 (PIG3), initially identified as a gene downstream of p53, plays an important role in the apoptotic process triggered by p53-mediated reactive oxygen species (ROS) production. Recently, several studies have suggested that PIG3 may play a role in various types of cancer. However, the functional significance of PIG3 in cancer remains unclear.

Clinical implications of APEX1 and Jagged1 as chemoresistance factors in biliary tract cancer.

Purpose: Biliary cancer is a highly malignant neoplasm with poor prognosis and most patients need to undergo palliative chemotherapy, however major clinical problem associated with the use of chemotherapy is chemoresistance. So far, we aimed at investigating clinical implications of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) and Jagged1 as chemoresistance factors in biliary tract cancer.

Methods: We used 5 human biliary tract cancer cell lines (SNU-245, SNU-308, SNU-478, SNU-1079, and SNU-1196), and investigated the chemosensitivity of APEX1 and Jagged1 through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Western blot.

p53R2 regulates thioredoxin reductase activity through interaction with TrxR2.

Ribonucleotide reductase small subunit p53R2 is a member of the ribonucleotide reductase family that supplies dNTPs for nuclear and mitochondrial DNA replication and repair. Here, we have identified a mitochondrial thioredoxin reductase 2 (TrxR2) as a novel p53R2-binding protein. We demonstrated a direct interaction between the two, and observed that p53R2 stimulated the enzymatic activity of TrxR in vitro.

Colon cancer progression is driven by APEX1-mediated upregulation of Jagged.

Aberrant expression of apurinic-apyrimidinic endonuclease-1 (APEX1) has been reported in numerous human solid tumors and is positively correlated with cancer progression; however, the role of APEX1 in tumor progression is poorly defined. Here, we show that APEX1 contributes to aggressive colon cancer behavior and functions as an upstream activator in the Jagged1/Notch signaling pathway. APEX1 overexpression or knockdown in human colon cancer cell lines induced profound changes in malignant properties such as cell proliferation, anchorage-independent growth, migration, invasion, and angiogenesis in vitro and in tumor formation and metastasis in mouse xenograft models.

A role of DNA-dependent protein kinase for the activation of AMP-activated protein kinase in response to glucose deprivation.

The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) plays an essential role in double-strand break repair by initially recognizing and binding to DNA breaks. Here, we show that DNA-PKcs interacts with the regulatory γ1 subunit of AMP-activated protein kinase (AMPK), a heterotrimeric enzyme that has been proposed to function as a "fuel gauge" to monitor changes in the energy status of cells and is controlled by the upstream kinases LKB1 and Ca²⁺/calmodulin-dependent kinase kinase (CaMKK). In co-immunoprecipitation analyses, DNA-PKcs and AMPKγ1 interacted physically in DNA-PKcs-proficient M059K cells but not in DNA-PKcs-deficient M059J cells.

Ape1/Ref-1 Stimulates GDNF/GFRalpha1-mediated Downstream Signaling and Neuroblastoma Proliferation.

We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor alpha1 (GFRalpha1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFRalpha1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFRalpha1 immunoreactivity in lipid rafts in response to GDNF.

Ape1/Ref-1 induces glial cell-derived neurotropic factor (GDNF) responsiveness by upregulating GDNF receptor alpha1 expression.

Apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) dysregulation has been identified in several human tumors and in patients with a variety of neurodegenerative diseases. However, the function of Ape1/Ref-1 is unclear. We show here that Ape1/Ref-1 increases the expression of glial cell-derived neurotropic factor (GDNF) receptor alpha1 (GFRalpha1), a key receptor for GDNF.

Oncogenic H-Ras up-regulates expression of Ku80 to protect cells from gamma-ray irradiation in NIH3T3 cells.

The Ras activation contributes to radioresistance, but the mechanism is unclear. This article shows that the expression of the dominant-positive H-Ras increased the Ku80 level, which is one of the key enzymes involved in repairing dsDNA breaks (DSB). After exposing the cells to ionizing radiation and analyzing them using an electrophoretic mobility shift assay and pulsed-field gel electrophoresis, it was found that activated H-Ras expression in NIH3T3 cells increases the DNA-binding activity of Ku80 and increases the DSB repair activity.

Small interfering RNA-induced suppression of ERCC1 enhances sensitivity of human cancer cells to cisplatin.

The level of excision repair cross-complementing 1 (ERCC1) gene expression, which is important in the repair of the cisplatin-DNA adducts, is reported to be related to the level of cisplatin resistance in tumor cells. Therefore, ERCC1 is an attractive target to confer increased cellular sensitivity to cisplatin-based chemotherapy. We designed, synthesized, and utilized small interfering RNAs (siRNAs) that were selective for ERCC1 and investigated their effectiveness in altering the repair capacity of the cells to cisplatin-DNA damage as well as the resistance of the cells to cisplatin.

Bcl-2 expression suppresses mismatch repair activity through inhibition of E2F transcriptional activity.

Bcl-2 stimulates mutagenesis after the exposure of cells to DNA-damaging agents. However, the biological mechanisms of Bcl-2-mediated mutagenesis have remained largely obscure. Here we demonstrate that the Bcl-2-mediated suppression of hMSH2 expression results in a reduced cellular capacity to repair mismatches.

Oncogenic H-Ras up-regulates expression of ERCC1 to protect cells from platinum-based anticancer agents.

Tumors frequently contain mutations in the ras genes, resulting in the constitutive activation of the Ras-activated signaling pathway. The activation of Ras is involved not only in tumor progression but also in the development of resistance of the tumor cells to platinum-based chemotherapeutic agents. To investigate the potential mechanisms underlying this resistance, we analyzed the effect of activated H-Ras on the expression of the nucleotide excision repair genes.