Anti-proliferative Effect of Engineered Neural Stem Cells Expressing Cytosine Deaminase and Interferon-β against Lymph Node–Derived Metastatic Colorectal Adenocarcinoma in Cellular and Xenograft Mouse Models / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Genetically engineered stem cells may be advantageous for gene therapy against various human cancers due to their inherent tumor-tropic properties. In this study, genetically engineered human neural stem cells (HB1.F3) expressing Escherichia coli cytosine deaminase (CD) (HB1.F3.CD) and human interferon-β (IFN-β) (HB1.F3.CD.IFN-β) were employed against lymph node–derived metastatic colorectal adenocarcinoma. MATERIALS AND METHODS: CD can convert a prodrug, 5-fluorocytosine (5-FC), to active 5-fluorouracil, which inhibits tumor growth through the inhibition of DNA synthesis,while IFN-β also strongly inhibits tumor growth by inducing the apoptotic process. In reverse transcription polymerase chain reaction analysis, we confirmed that HB1.F3.CD cells expressed the CD gene and HB1.F3.CD.IFN-β cells expressed both CD and IFN-β genes. RESULTS: In results of a modified trans-well migration assay, HB1.F3.CD and HB1.F3.CD.IFN-β cells selectively migrated toward SW-620, human lymph node–derived metastatic colorectal adenocarcinoma cells. The viability of SW-620 cells was significantly reduced when co-cultured with HB1.F3.CD or HB1.F3.CD.IFN-β cells in the presence of 5-FC. In addition, it was found that the tumor-tropic properties of these engineered human neural stem cells (hNSCs) were attributed to chemoattractant molecules including stromal cell-derived factor 1, c-Kit, urokinase receptor, urokinase-type plasminogen activator, and C-C chemokine receptor type 2 secreted by SW-620 cells. In a xenograft mouse model, treatment with hNSC resulted in significantly inhibited growth of the tumor mass without virulent effects on the animals. CONCLUSION: The current results indicate that engineered hNSCs and a prodrug treatment inhibited the growth of SW-620 cells. Therefore, hNSC therapy may be a clinically effective tool for the treatment of lymph node metastatic colorectal cancer.

Nuclear localization of Obox4 is dependent on its homeobox domain / 대한생식의학회지

OBJECTIVE: Oocyte-specific homeobox 4 (Obox4) is preferentially expressed in oocytes and plays an important role in the completion of meiosis of oocytes. However, the Obox4 expression pattern has not been reported yet. In this study, we investigated the subcellular localization of Obox4 using a green fluorescent protein (GFP) fusion expression system. METHODS: Three regions of Obox4 were divided and fused to the GFP expression vector. The partly deleted homeodomain (HD) regions of Obox4 were also fused to the GFP expression vector. The recombinant vectors were transfected into HEK-293T cells plated onto coated glass coverslips. The transfected cells were stained with 4',6-diamidino-2-phenylindol and photographed using a fluorescence microscope. RESULTS: Mutants containing the HD region as well as full-length Obox4 were clearly localized to the nucleus. In contrast, the other mutants of either the N-terminal or C-terminal region without HD had impaired nuclear localization. We also found that the N-terminal and C-terminal of the Obox HD contributed to nuclear localization and the entire HD was necessary for nuclear localization of Obox4. CONCLUSION: Based on the results of the present study, we demonstrated that the intact HD region of Obox4 is responsible for the nuclear localization of Obox4 protein in cells.

Lin28 regulates the expression of neuropeptide Y receptors and oocyte-specific homeobox genes in mouse embryonic stem cells / 대한생식의학회지

OBJECTIVE: Lin28 has been known to control the proliferation and pluripotency of embryonic stem cells. The purpose of this study was to determine the downstream effectors of Lin28 in mouse embryonic stem cells (mESCs) by RNA interference and microarray analysis. METHODS: The control siRNA and Lin28 siRNA (Dharmacon) were transfected into mESCs. Total RNA was prepared from each type of transfected mESC and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis to confirm the downregulation of Lin28. The RNAs were labeled and hybridized with an Affymetrix Gene-Chip Mouse Genome 430 2.0 array. The data analysis was accomplished by GenPlex 3.0 software. The expression levels of selected genes were confirmed by quantitative real-time RT-PCR. RESULTS: According to the statistical analysis of the cDNA microarray, a total of 500 genes were altered in Lin28-downregulated mESCs (up-regulated, 384; down-regulated, 116). After differentially expressed gene filtering, 31 genes were selected as candidate genes regulated by Lin28 downregulation. Among them, neuropeptide Y5 receptor and oocyte-specific homeobox 5 genes were significantly upregulated in Lin28-downregulated mESCs. We also showed that the families of neuropeptide Y receptor (Npyr) and oocyte-specific homeobox (Obox) genes were upregulated by downregulation of Lin28. CONCLUSION: Based on the results of this study, we suggest that Lin28 controls the characteristics of mESCs through the regulation of effectors such as the Npyr and Obox families.

A Single Institution's Experience of Endoscopic Retrograde Cholangiopancreaticography in the Eldery Patients: Outcomes, Safety and Complications / 대한소화기학회지

BACKGROUND/AIMS: As the population ages, endoscopic retrograde cholangiopancreaticography (ERCP) is being used increasingly as a diagnostic and therapeutic tool for elderly patients with pancreatobiliary disease. The aim of this study was to assess the outcomes, safety and complications associated with ERCP performed in the elderly patients. METHODS: We retrospectively reviewed the medical record of 596 patients who were 50 years of age or older and underwent ERCP from January 2005 to September 2010. The patients were classified into two groups according to the age: non-elderly, 50-74 years old and elderly, > or =75 years old. Comparisons were made between two groups. RESULTS: Five hundred and ninety-six patients (132 elderly and 464 non-elderly patients) were enrolled. The success rate of ERCP was 89.4% in the elderly and 91.9% in the non-elderly. The major complications were occurred in 11 patients of the elderly and 16 of the non-elderly, and the complication rate was significantly higher in the elderly compared to the non-elderly (8.3% vs. 3.4%, p=0.011). Pancreatitis occurred in 2 elderly patients and 10 non-elderly patients (1.5% vs. 2.1%, p=1.0). There was a higher rate of bleeding in the elderly patients (4.5% vs. 1.3%, p=0.01). CONCLUSIONS: ERCP is effective and safe even in elderly patients. Outcomes of diagnostic and therapeutic ERCP in the elderly patients were similar to those in non-elderly patients. Elderly patients undergoing ERCP carried similar risk of pancreatitis but a higher risk of bleeding and perforation compared to non-elderly patients.

Effect of Previous Abdominal or Pelvic Surgery on Colonoscopy / 대한소화기내시경학회지

BACKGROUND/AIMS: A number of studies have reported wide variability in the colonoscope insertion time among patients who had prior abdominal surgery. The aim of this study was to investigate the effect of abdominal surgery on colonoscope insertion time. METHODS: The subjects were 192 patients with prior abdominal surgery, among 3,600 patients who underwent a colonoscopy at Samsung Changwon Hospital from May 2008 to May 2010. We collected the following data: insertion time, age, gender, height, weight, BMI, waist circumference, method of abdominal surgery, and the degree of bowel cleanliness. Previous abdominal operations were divided into colectomy, non-colectomy abdominal surgery, pelvic surgery, and laparoscopic surgery groups. RESULTS: The average colonoscope insertion time in patients with prior abdominal surgery (7.73+/-5.95 min) was longer than that of the non-surgery group (6.4+/-3.88 min). Patients in the colectomy groups were older and had a shorter insertion time (5.11+/-3.32 min) than patients in the other groups. CONCLUSIONS: Insertion of a colonoscope in patients with previous abdominal surgery was more difficult than that in the control group, except the colectomy group.

A case of stress-induced cardiomyopathy with an "inverted Takotsubo" contractile pattern / 대한내과학회지

Stress-induced cardiomyopathy, known as Takotsubo cardiomyopathy, is a newly described clinical entity characterized by transient left ventricular apical ballooning and left ventricular apical dyskinesis, with no significant stenosis on the coronary angiogram. We describe a patient who had transient cardiomyopathy with akinesia of the basal portions of the left ventricle and hyperkinesia of the apex. This is the first case of stress-induced cardiomyopathy with an "inverted Takotsubo" contractile pattern triggered by emotional stress in Korea. The cause of stress-induced cardiomyopathy is unclear, but catecholamines probably play a role in this syndrome. This entity could provide clues to the pathophysiology underlying stress-induced cardiomyopathy.

A Case of Primary Renal Amyloidosis with Fulminant Hepatic Failure / 대한신장학회지

We report the case of a patient with primary renal amyloidosis, who was progressed to fulminant hepatic failure. A 68-year-old man visited our hospital for evaluation of anorexia, weight loss and hepatomegaly. Laboratory examination revealed proteinuria and azotemia. He was confirmed to have primary amyloidosis by renal biopsy. His renal function progressed to deteriorate rapidly with marked deterioration of liver function with cholestasis. Peritoneal dialysis and steroid therapy were started for reduction of urine output and rapid progression of azotemia, and aggravation of liver function. Azotemia was improved after peritoneal dialysis but the liver function worsened leading to hepatic failure, causing death. If jaundice has progressed in any patients with primary amyloidosis, liver transplantation and stem cell transplantation should be considered for preparation of hepatic failure.

A Case of Anuric Acute Renal Failure, Acute Hepatitis and Rhabdomyolysis occurred after Carp Bile Ingestion / 대한신장학회지

Gall bladder of a common carp is taken in some areas of Asia as a traditional medicine for improvement of their general health problems like hypertension, poor visual acuity, and impotence. Many cases have been reported on acute hepatitis, acute renal failure, gastrointestinal problems and neurological symptoms following ingestion of raw carp bile juice. We experienced a case of anuric ARF, acute hepatitis, and rhabdomyolysis that developed after indigestion of raw carp bile juice, not yet seen in previous studies. In this case, anuric state of patient was resolved after 4 days with continuous renal replacement therapy. Thus we report this case with review of literature.

Acute Renal Failure Due to Severe Stenosis of Fibromuscular Dysplasia in a Single Kidney / 대한신장학회지

Among complications of fibromuscular dysplasia are uncontrolled hypertension, aneurysm and, albeit very rare, renal failure, especially in a single kidney. We report a case of severe stenosis of fibromuscular dysplasia leading to renal failure, in need of temporary hemodialysis in 29-year-old hypertensive woman. When she was 13-year-old, she underwent a left nephrectomy because of the left renal cyst and she was treated with antihypertensive medication for several years. A few day before admission, she complained of oliguria, generalized edema and aggravated dyspnea. On the day of admission, she took emergency hemodialysis. A renal angiogram showed focal irregular stenosis in the right proximal renal artery, compatible with fibromuscular dysplasia; therefore, we performed percutaneous renal artery angioplasty. Following successful renal angioplasty, her urine output increased and creatinine level was normalized.

A Case of Spontaneous Renal Artery and Celiac Artery Dissection in Healthy Man / 대한신장학회지

Spontaneous dissection of peripheral arteries unrelated to the aorta is rare. Cases reported in the literature have involved the renal arteries, the coronary arteries, the cerebral arteries, and visceral arteries, in order of incidence. There is no consensus yet on indications for medical or surgical therapeutic modality. As a consequence of the rarity of spontaneous dissection of peripheral arteries, its natural history has been poorly described. A healthy 37-year-old male with normotension was admitted with an acute onset of left flank pain. Physical examination turned out an unremarkable result. Right renal infarction and splenic infarction was diagnosed by abdominal computed tomography. A spiral CT angiogram and angiography showed dissection of main right renal artery and celiac artery with involvement of branches. One year later, he has remained well and normotensive without treatment. To our knowledge, this is the first case of spontaneous renal and celiac artery dissection in normotensive patient in Korea.

Autocrine Extracellular Signal-regulated Kinase Activation in Normal Human Keratinocytes is not Interrupted by Calcium Triggering and is Involved in the Control of Cell Cycle at the Early Stage of Calciuminduced Differentiation

Normal human epidermal keratinocytes (NHEK) respond to the autocrine activated extracellular signal-regulated kinase (ERK) signaling pathway, which contributes to the survival of keratinocytes. However, during the condition of calcium-induced differentiation, how the autocrine ERK signaling is regulated and affected is poorly understood. The purpose of this study was to understand and to obtain clues to the possible function of the autocrine ERK activation during the calcium-induced differentiation of NHEK. We demonstrated that the autocrine activated ERK was not interrupted by calcium triggering and that it was sustained for at least one day after changing the medium. We also found that the autocrine ERK activation was associated with the expression of cyclin D1 and the cell cycle regulation at the early stage of calcium triggering by treating the cells with the mitogen-activated protein kinase inhibitor PD98059. However, the PD98059 treatment did not have a significant influence on the expression of involucrin and loricrin. In addition, we demonstrated that autocrine ERK activation was associated with protein kinase C and p38MAPK signaling. We suggest that the activation of autocrine ERK is not interrupted by calcium triggering and it might participate in cell growth during the early stage of calcium-induced differentiation in NHEK.

Analysis of the functional domain of the hepatitis B virus X gene product fused to the GAL4 binding domain

No abstract available.