BACKGROUND: Chronic myelogenous leukemia is a chronic myeloproliferative disorder characterized by leukocytosis with myeloid elements at all stages of differentiation, t(9;22)(q34;q11) and bcr/abl rearrangement. We studied hydroxyurea induced apoptotic changes such as externalization of phosphatidylserine, caspase activities on human chronic myelogenous leukemic cell line, K562 cells. METHODS: K562 cells were grown in RPMI 1640 supplemented with 10% fetal bovine serum and treated hydroxyurea. Viability was examined by MTT assay. Apoptosis were examined by annexin V stain, caspase (such as caspase-, caspase-, caspase-, caspase-, and caspase-) activities, and DNA fragmentation. RESULTS: The viability of K562 cells were markedly decreased in a dose dependent manner of hydroxyurea. Phosphatidylserine externalization was detected by annexin V stain after 3 hours in hydroxyurea treated K562 cells and the value of lactate dehydrogenase was not significantly changed in their culture media. The upstream effector of caspase- was slightly increased and had influenced on caspase-. And downstream acting caspase protease of caspase- was markedly increased in a time dependent manner at hydroxyurea treated K562 cells. In addition, however the activities of caspase- and caspase- were not increased. We also found DNA fragmentation at hydroxyurea treated K562 cells between 48 hours and 72 hours on agarose gel electrophoresis. CONCLUSIONS: Hydroxyurea induces apoptotic change in K562 cells via externalization of phosphatidylserine, activations of caspase-, caspase-, caspase- proteases, and DNA fragmentation.
Annexin A5 ; Apoptosis ; Cell Line* ; Culture Media ; DNA Fragmentation ; Electrophoresis, Agar Gel ; Humans ; Hydroxyurea* ; K562 Cells* ; L-Lactate Dehydrogenase ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukocytosis ; Myeloproliferative Disorders ; Peptide Hydrolases

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.
Apoptosis ; Autophagy* ; Caspase 3 ; Chloroquine ; Endothelial Cells* ; Fibroblast Growth Factor 2 ; Helminths ; Intercellular Signaling Peptides and Proteins ; Mebendazole* ; Microtubules ; Phosphorylation ; Phosphotransferases ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factor A

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome, typically characterized by multiple colorectal adenomas and increased incidence of colorectal carcinomas if left untreated. It is caused by germline mutations of the adenomatous polyposis coli (APC) gene, which has been mapped on chromosome 5q21, and is accompanied by various benign and malignant extracolonic manifestations. The prevalence of thyroid tumors developing in patients with FAP is about 1~2%, are associated with FAP and have certain characteristics; mean age of tumor diagnosis at less than 30 years of age, the pathology is the papillary histiotype in more than 90% of cases, including a so-called cribriform- morular pattern, and multifocality is a frequent feature. In a genetic analysis, thyroid cancer in FAP usually has a mutation in the 5-portion of exon 15 between 778 and 1309, on chromosome 5q21. Also, the ret/PTC (especially ret/PTC1 and ret/PTC3) and p53 genes are thought probably to be associated with thyroid cancer in FAP patients. A case of familial adenomatous polyposis, accompanied by thyroid papillary cancer, was experienced in a 29 year-old female. She had hundreds of adenomas throughout the entire colon and congenital hypertrophy of the retinal pigment epithelium (CHRPE). The pathological finding of thyroid cancer was revealed as a mixture of cribriform, trabecular and papillary patterns. In a genetic analysis, she and her brother had a germline mutation of the APC gene at codon 1309. In Korea, there has been no previous case of cribriform-morular pattern and familial genetic analysis in FAP associated with thyroid cancer. Therefore, this case is reported, with a review of the literature
Adenoma ; Adenomatous Polyposis Coli* ; Adult ; Codon ; Colon ; Colorectal Neoplasms ; Diagnosis ; Exons ; Female ; Genes, APC ; Genes, p53 ; Germ-Line Mutation ; Humans ; Hypertrophy ; Incidence ; Korea ; Pathology ; Prevalence ; Retinal Pigment Epithelium ; Siblings ; Thyroid Gland* ; Thyroid Neoplasms

PURPOSE: Constipation is a frequent complaint among dialysis patients. However, factors that contribute to constipation in these patients have not been evaluated rigorously. The aim of study was to assess the prevalence and factors that contribute to constipation in patients with End-Stage Renal Disease (ESRD) undergoing hemodialysis (HD) or peritoneal dialysis (PD). METHODS: Patients undergoing HD or PD for more than six months in the six dialysis centers were asked to complete a self-administered questionnaire that is designed to assess constipation by Rome- III criteria. Beck depression inventory (BDI) were assessed. A total of 146 patients (HD 91, PD 55) completed the study. RESULTS: The prevalence of constipation was 33% in 91 HD patients and 31% in 55 PD patients. Prevalence of constipation was 32% and did not differ by dialysis mode. Older age, unemployed state, high cumulative illness rating scale and high BDI were associated with constipation. In multivariate analysis, BDI was an independent factor associated with constipation. The prevalence of constipation was 18% and 50% for patients with BDI <15 and > or =15, respectively. The odd ratio for constipation in patients with BDI > or =15 was 3.4 (95% CI, 1.4-8.1). CONCLUSION: Careful psychogenic attention must be paid to ESRD patients with constipation.
Constipation ; Depression ; Dialysis ; Humans ; Kidney Failure, Chronic ; Multivariate Analysis ; Peritoneal Dialysis ; Prevalence ; Renal Dialysis ; Surveys and Questionnaires

Hepatoid adenocarcinoma is a rare variant of adenocarcinoma of the stomach. The tumor has been found to be an alpha-fetoprotein (AFP) producing carcinoma arising in extrahepatic organs, and it mimics hepatocellular carcinoma in terms of morphology and function. Vascular invasion, usually prominent, is often complicated by extensive liver metastases, and vascular permeation, especially in the veins, has been described as a characteristic finding of this tumor. A patient with hepatoid adenocarcinoma of the stomach with a huge mass is described. Gastrofiberscopy revealed an elevated lesion with a central depression on the greater curvature of the antrum and with extrinsic compression on the lesser curvature and the duodenum. Computed tomography revealed a large lobulated mass in the lesser curvature of the stomach, attached from the liver, gall bladder and porta hepatitis to the pancreas. The AFP serum level was markedly elevated. After a diagnosis was made of AFP-producing stomach carcinoma with huge lymph node metastasis, subtotal gastectomy with wedge resection of the liver, and cholecystectomy including the huge mass ware performed. Microscopically, the tumor and intraabdominal huge mass showed mainly hepatoid differentiation. The tumor showed immunohistochemical positivity for AFP and huge lesser omental metastasis with adhesion to the liver and extensive venous invasion. Lymph node metastasis was not found. According to these histopathological findings, the tumor was diagnosed as hepatoid adenocarcinoma of the stomach with venous invasion. We report this rare variant of adenocarcinoma of the stomach, which mimics hepatocellular carcinoma in its propensity for venous permeation.
Adenocarcinoma* ; alpha-Fetoproteins ; Carcinoma, Hepatocellular ; Cholecystectomy ; Depression ; Diagnosis ; Duodenum ; Hepatitis ; Humans ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Pancreas ; Stomach* ; Urinary Bladder ; Veins

It is known that early childhood wheezing associated with sensitization to allergens, including food, has an increased risk of developing asthma later during school age. Gastroesophageal reflux (GER) is well known to be associated with asthma. The purpose of this study was to determine whether there is an association between silent GER and food sensitization in infants and young children with recurrent wheezing. Eighty-five infants or young children with recurrent wheezing, and no gastrointestinal symptoms, underwent 24 hr esophageal pH monitoring, as well as total serum IgE and specific IgE testing for eggs and milk. Among the 85 subjects, 48.2% had significant GER. There was no significant difference in the GER between atopic and non-atopic recurrent wheezers (41.7% and 50.8%, respectively). The sensitization rate to food (eggs or milk) was 12.2% and 20.5% in the GER and non-GER groups, respectively and showed no statistically significant difference between the two groups (P=0.34). In conclusion, about half of infants and young children with recurrent wheezing and no gastrointestinal symptoms have silent GER. The silent GER may not contribute to food sensitization in infants and young children with recurrent wheezing.
Allergens/immunology ; Child, Preschool ; Esophageal pH Monitoring ; Female ; *Food Hypersensitivity/etiology/immunology ; *Gastroesophageal Reflux/complications/immunology ; Humans ; Infant ; Male ; *Respiratory Sounds/etiology/immunology

Indigo carmine has been used for eight decades with few adverse effects. Several of our patients, however, experienced severe hypotensive episodes after indigo carmine administration within a period of one month. Analysis of the raw materials used to formulate the preparation of indigo carmine we used showed that they contained impurities. Following recall of these impure materials, none of our patients experienced further hypotensive episodes.
Humans ; Hypotension ; Indigo Carmine ; Indoles

Although the papillary thyroid carcinoma generally follows an indolent course characterized by slow growth and abscence of distant metastasis, distant metastases to extrathyroid organ may occur in the lung, bone and brain in about 5% of patients. The lung metastases are usually diagnosed by plain X-ray, chest CT and 131I whole body scan. However, we present a case of papillary thyroid carcinoma with microscopic pulmonary metastasis that could not be detected by conventional method, such as chest X-ray, chest CT and 131I whole body scan. A 62-year-old female visited due to traumatic hemopneumothorax. In the pathology of resected tissues from lacerated lung parenchyme, metastatic papillary carcinoma was diagnosed without evidence of abnormality in radiologic examination and we diagnosed and treated an asymptomatic papillary thyroid carcinoma.
Brain ; Carcinoma, Papillary ; Female ; Hemopneumothorax ; Humans ; Lung ; Middle Aged ; Neoplasm Metastasis* ; Pathology ; Thorax ; Thyroid Gland* ; Thyroid Neoplasms* ; Tomography, X-Ray Computed ; Whole Body Imaging

BACKGROUND/AIMS: With improvements in the survival of liver transplantation (LT) recipients, the focus is shifting to patient quality of life (QOL), and employment is an important factor in aiding the social reintegration of LT patients. This study aims to evaluate the current employment status of liver graft recipients and various factors that may hinder reemployment. METHODS: Fifty patients above age 18 who underwent either living or deceased donor LT at a single center from March 2009 to July 2016 were interviewed during their visit to the outpatient clinic. The internally developed questionnaire consisted of 10 items. The Karnofsky Performance Scale and EQ-5D were used to evaluate patient function and QOL. RESULTS: A total of 25 (50%) patients returned to work after transplantation (the working group), and 21 (84%) patients in the working group returned to work within the first year after transplantation. In the non-working group (n=25), 17 (68%) answered that their health was the reason for unemployment. Fatigue and weakness were the most frequent symptoms. CONCLUSIONS: The data shows that as many as 50% of total patients returned to work after receiving LT. Fatigue and weakness were the most common complaints of the unemployed group, and resolving the causes of these symptoms may help to increase the employment rate.
Ambulatory Care Facilities ; Employment ; Fatigue* ; Humans ; Liver Transplantation* ; Liver* ; Quality of Life ; Tissue Donors ; Transplants ; Unemployment

The purpose of this study was to investigate the prevalence, clinical characteristics, and management of functional constipation at pediatric gastroenterology clinics. A prospective survey using the Rome III criteria was distributed to a group of parents of children with a constipation history and its control group in May 2008. The mean prevalence of constipation was 6.4%, which was similar to those in other countries. Statistically significant variables for children without constipation were that more children had a body mass index of below the 10th percentile even though they received more mother's care and ate balanced meals compared to the constipation group. Meanwhile, the constipation group frequently showed a history of constipation in infancy, picky-eating, lack of exercise, and retentive posturing. When analyzed with the Rome III criteria, the children showed greater than 60% rate of hard stools, painful stools, a history of large fecal mass in rectum, and its disappearance of constipation symptoms after passing a large stool. Our study found different approaches amongst pediatric gastroenterologists like rectal examinations, disimpaction, or drug treatment. Several factors addressed in our study can provide better guidelines for clinicians treating constipation and its future research.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; Constipation/*diagnosis/drug therapy/epidemiology ; Female ; Hospitals ; Humans ; Infant ; Laxatives/therapeutic use ; Male ; Prevalence ; Prospective Studies ; Rectum/physiopathology ; Severity of Illness Index