APE1 Promotes Pancreatic Cancer Proliferation through GFRα1/Src/ERK Axis-Cascade Signaling in Response to GDNF

Pancreatic cancer is the worst exocrine gastrointestinal cancer leading to the highest mortality. Recent studies reported that aberrant expression of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is involved in uncontrolled cell growth. However, the molecular mechanism of APE1 biological role remains unrevealed in pancreatic cancer progression. Here, we demonstrate that APE1 accelerates pancreatic cancer cell proliferation through glial cell line-derived neurotrophic factor (GDNF)/glial factor receptor α1 (GFRα1)/Src/ERK axis-cascade signaling. The proliferation of endogenous APE1 expressed-MIA PaCa-2, a human pancreatic carcinoma cell line, was increased by treatment with GDNF, a ligand of GFRα1. Either of downregulated APE1 or GFRα1 expression using small interference RNA (siRNA) inhibited GDNF-induced cancer cell proliferation. The MEK-1 inhibitor PD98059 decreased GDNF-induced MIA PaCa-2 cell proliferation. Src inactivation by either its siRNA or Src inhibitor decreased ERK-phosphorylation in response to GDNF in MIA PaCa-2 cells. Overexpression of GFRα1 in APE1-deficient MIA PaCa-2 cells activated the phosphorylation of Src and ERK. The expression of both APE1 and GFRα1 was gradually increased as progressing pancreatic cancer grades. Our results highlight a critical role for APE1 in GDNF-induced pancreatic cancer cell proliferation through APE1/GFRα1/Src/ERK axis-cascade signaling and provide evidence for future potential therapeutic drug targets for the treatment of pancreatic cancer

Imaging Findings of Localized Lymphoid Hyperplasia of the Pancreas: a Case Report

We report here on a case of localized lymphoid hyperplasia of the pancreas in a 70-year-old man which manifested as double lesions (uncinate process and tail) in the organ. The lesions were incidentally detected as hypoechoic lesions on ultrasonography and they appeared as delayed enhancing lesions on the contrast-enhanced dynamic CT and MRI. Total pancreatectomy was performed, because malignant tumor could not be excluded according to the preoperative imaging studies and the endoscopic ultrasound-guided biopsy failed. Pathology revealed localized lymphoid hyperplasia. The patient had an uneventful postoperative course. He has been alive for 18 months after surgery

Prostate Cancer with Solitary Metastases to the Bilateral Testis

We present the case of an 81-year-old patient with testicular metastasis from prostate carcinoma. After the initial diagnosis of prostate cancer, he had an 8-year course of hormonal therapy and showed no clinical evidence of metastasis to other organs. Asymptomatic metastasis of prostate carcinoma to the testis is a rare clinical condition. We diagnosed his condition, based on histopathology following a subcapsular orchiectomy and transurethral resection of the prostate

Clinico-pathological Characteristics of Congenital Pulmonary Lymphangiectasis: Report of Two Cases

Congenital pulmonary lymphangiectasis (CPL) is a rare, poorly documented disease, characterized by abnormal dilatation of pulmonary lymphatics without lymphatic proliferation. This disease is seen almost exclusively in infancy and early childhood. It can usually be divided into primary (congenital) and secondary forms. The primary form presents in neonates, and the patients mostly die due to the respiratory distress, shortly after birth. The authors experienced two cases of primary CPL in a 13-day-old male neonate and a one-day-old male neonate, showing prominent lymphatic dilatation in the septal, subpleural, and peri-bronchial tissue throughout both lungs. The latter case was associated with congenital cardiac anomaly including single ventricle. These are unique cases of CPL in Korea of which the diagnosis was established through post-mortem examination. Therefore, the authors report these two cases with primary CPL with a review of the literature

A Case of Pulmonary Alveolar Microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare disease with unknown etiology and pathogenesis. It is characterized by diffuse, innumerable, and minute calculi, called microlithiasis in the alveoli. More than half of reported cases are asymptomatic at the time of diagnosis. We describe the first case of PAM in Korea. A 19-yr-old man without respiratory symptoms presented with interstitial thickening on the chest radiograph. His chest high resolution CT scan showed diffusely scattered, ill defined tiny micronodules and interstitial thickening. Open lung biopsy confirmed the diagnosis of PAM. He was followed up for 6 months without treatment, and no progression was noticed

A case of bilateral submandibular gland mucoceles in a 16-month-old child

Mucoceles are common benign cystic lesions of the oral cavity that develop following extravasation or retention of mucous material from the major or minor salivary glands. Mucoceles are usually located in the lower lip (60 to 70% of cases), and the floor of the mouth is only involved in 6 to 15% of cases. Submandibular gland mucocele is extremely rare but should be considered in the differential diagnosis of swelling at the submandibular triangle in young children. We present the rare case of a 16-month-old child who was diagnosed with bilateral submandibular gland mucocele, presenting as serial swellings in both submandibular regions. We removed the cystic mass with the submandibular and sublingual glands to prevent recurrence

Long Term Follow-up Results of External Beam Radiotherapy as Primary Treatment for Retinoblastoma

The authors reviewed their experiences of external beam radiotherapy (EBR) as an initial treatment in retinoblastoma patients to determine its long-term effect on subsequent tumor control and complications. A total of 32 eyes in 25 patients that underwent EBR for retinoblastoma were reviewed retrospectively. The patients consisted of 21 boys and 4 girls of median age at treatment of 7.1 months. Radiation doses ranged from 35 to 59.4 Gy. The 10-yr ocular and patient survivals were 75.4% and 92.3%, respectively. Nine of the 32 eyes progressed; 7 of these were enucleated and 2 were salvaged by focal treatment. According to the Reese-Ellsworth classification, 4 of 5 eyes of Group II, 13 of 16 Group III eyes, 2 of 4 Group IV eyes, and 5 of 7 Group V eyes were retained, and of the 32 eyes, 13 had visual acuity better than 20/200. Eleven patients experienced a radiation-induced complication. No patient developed a second malignancy during follow-up. Despite the limited number of patients enrolled, EBR may provide a mean of preserving eyeball and vision for some advanced lesions