Inhibition of HIF1α and PDK Induces Cell Death of Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia. Under normoxia, the basal expressions of HIF1α and the glycolysis-associated genes, PDK1, PDK3, and GLUT1, were relatively low in U251 and GBM28, while their basal expressions were high in GBM37. Under hypoxia, the expressions of these genes were enhanced further in all three GBMs. Treatment with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), induced cell death in GBM28 and GBM37 maintained under normoxia, whereas DCA effects disappeared under hypoxia, suggesting that hypoxic adaptation dominated DCA effects in these GBMs. In contrast, the inhibition of HIF1α with chrysin suppressed the expression of PDK1, PDK3, and GLUT1 and markedly promoted cell death of all GBMs under both normoxia and hypoxia. Interestingly, however, GBMs treated with chrysin under hypoxia still sustained higher viability than those under normoxia, and chrysin and DCA co-treatment was unable to eliminate this hypoxia-dependent resistance. Together, these results suggest that hypoxic adaptation is critical for maintaining viability of GBMs, and targeting hypoxic adaptation can be an important treatment option for GBMs.

The Trend of Eradication Rates of First-line Triple Therapy for Helicobacter pylori Infection: Single Center Experience for Recent Eight Years / 대한소화기학회지

BACKGROUND/AIMS: The prevalence of antibiotic resistance in Helicobacter pylori (H. pylori) infection has been reported to be increasing. However, the recent trend of eradication rates of H. pylori using first-line triple regimens has been rarely issued. Therefore, we aimed to determine the trend of H. pylori eradication rates in single center for recent eight years. METHODS: From January 1998 through October 2005, H. pylori eradication rates in 525 patients with H. pylori-positive peptic ulcer disease who received one-week triple regimens were retrospectively evaluated according to years, regimens, and ulcer locations. RESULTS: The overall H. pylori eradication rate was 78.7%. Yearly eradication rates from the year 1998 to 2005 were 83.7%, 80.4%, 81.4%, 78.8%, 75.3%, 77.6%, 78.9% and 77.6% consecutively by per-protocol analysis, However, no definite evidence of decreasing tendency of eradication rate was seen during the past eight years (p=0.419). Furthermore, there was no significant difference in the eradication rates according to the ulcer locations and regimens. CONCLUSIONS: Although it is found that there is no definite statistical evidence of decreasing trend for H. pylori eradication rate during past eight years, those for recent 5 years were lower than 80%, which suggests that we should scrutinize the trend of first-line H. pylori eradication rate, and concern for the expected lower rates in the near future.

A Case of Pancreatic Somatostatinoma / 대한소화기학회지

Somatostatinoma is a rare neoplasm usually arising from the pancreas and duodenum which typically presents with indolent, nonspecific symptoms in the absence of systemic neuroendocrine manifestations that characterize somatostatinoma syndrome. It accounts for less than 1% of all gastrointestinal endocrine tumors with an annual incidence of 1 per 40 million. It is often associated with regional and/or portal metastasis at the time of diagnosis, and complete tumor resection is possible only in 60% to 70% of cases. We experienced a case of pancreatic somatostatinoma recently. A 51-year-old woman presented with right upper quadrant abdominal pain and loose stool for one month. A hypermetabolic lesion in the pancreatic head was detected on positron emission tomography-CT (PET-CT) scan. The tumor was resected by pylorus preserving pancreaticoduodenectomy. Immunohistochemical staining of the tumor tissue exhibited diffuse positivity for somatostatin, but was negative for insulin and glucagon. Herein, we report a case of pancreatic somatostatinoma diagnosed postoperatively.

Acute renal failure due to bilateral pyelonephritis / 대한내과학회지

Acute renal failure is a rare complication of acute pyelonephritis. Therefore, acute pyelonephritis is not usually considered in the differential diagnosis of acute renal failure. However, it is important to consider this entity because of potential for recovery of renal function if appropriate early antibiotics are instituted. We report a case of biopsy proven acute pyelonephritis which was manifested as acute renal failure. A 38 year old women was admitted to this hospital owing to abdominal distension and generalized edema. On admission she was started on hemodialysis because of severe hyperkalemia and marked uremic sypmtoms. She had pyuria and hematuria, but no organism was isolated at urine. We initially don't know the cause of renal failure. She was improved with antimicrobial therapy and hemodialysis. A kidney biopsy was performed on the 26th hospital day because of persistent proteinuria. Microscopic examination revealed focal tubular atrophy, necrosis or loss with heavy infilteration of leukocytes and histocytes in interstitium. Atrophic tubules contain pus casts. The patient was treated with ciprofloxacin for 4 weeks. At about 2 month follow up, proteinuria completely disappeared and serum creatinine level decreased to 1.0 mg/dL.

Usefulness of Magnifying Chromoscopy in Ulcerative Colitis / 대한소화기내시경학회지

BACKGROUND/AIMS: Ulcerative colitis is an inflammatory bowel disease with unknown etiology, which has waxed and waned course. It is diagnosed by colon study, pathology, and especially colonoscopy. It is difficult to differentiate between ulcerative colitis and other infectious colitis, especially amebic colitis, and to confirm of remnant lesion by endoscopic findings. METHODS: Magnifying colonoscopy has 100 time magnifying power compared to 30 time of conventional colonoscopy. By spraying 0.2% indigo carmine dye, we evaluated the magnifying and microscopic findings of 31 colonic mucosa of 23 patients with ulcerative colitis. RESULTS: Initial and magnifying chromoscopic findings in ulcerative colitis were loss of cryptal opening 72% (13/18), loss of submucosal vessel 89% (16/18), mucosal denudation (or microscopic erosion) 83% (15/18), and mucosal unevenness 94% (17/18). Recovery rate of magnifying chromoscopic findings after treatment in ulcerative colitis were in crytal opening 80% (8/10), submucosal vascularity 60% (6/10), mucosal denudation (microscopic erosion) 30% (3/10), and in mucosal unevenness 40% (4/10). CONCLUSIONS: It is suggested that magnifying chromoscopic findings in ulcerative colitis may be useful in initial diagnosis and confirmation of remnant lesion, but, not in prediction of clinical severity.

Exercise Provocation Test in Patients with Vasospastic Angina: Graded vs. Non-Graded Exercise Test

BACKGROUND AND OBJECTIVES: We investigated in patients with coronary vasospastic angina whether the exercise ECG test results are influenced by the different modes of exercise load and compared the clinical characteristics including coronary risk factors between patients with positive and negative exercise tests. MATERIALS AND METHODS: This study comprised 34 patients with documented coronary artery spasm without significant stenosis (coronary artery luminal diameter narrowing 50%, <70% of luminal diameter) or total cholesterol level between patients with positive and negative results. In 18 typical variant angina patients by clinical history, 8 of 10 patients with high disease activity (5 times or more attack per week) manifested positive result by GET or NGET, whereas 4 of 8 patients with low disease activity (80 vs. 50%, P=NS). CONCLUSION: In patients with coronary vasospastic angina, sudden rapid exercise could induce more frequently coronary artery spasm than multistage exercise. The result of an exercise test may not be correlated with coronary risk factors, coronary anatomy, effort chest pain, and the disease activity.