The human telomerase reverse transcriptase (hTERT) promoter can be used for the tumor-specific expression of transgenes in order to induce selective cancer cell death. The hTERT core promoter is active in cancer cells but not in normal cells. To examine whether the combination of TNF-related apoptosis inducing ligand (TRAIL) treatment and cancer cell-selective expression of the TRAIL-death receptor could induce cell death in TRAIL-resistant cancer cells, we generated a death receptor-4 (DR4)-expressing adenovirus (Ad-hTERT-DR4), in which the expression of DR4 is driven by the hTERT promoter. Upon infection, DR4 expression was slightly increased in cancer cell lines, and cell death was observed in TRAIL-resistant cancer cell lines but not in normal human cells when DR4 infection was combined with TRAIL treatment. We also generated an adenovirus that expresses a secretable isoleucine zipper (ILZ)-fused, extracellular portion of TRAIL (Ad-ILZ-TRAIL). In cells infected with Ad-ILZ-TRAIL, TRAIL was expressed, secreted, oligomerized and biologically active in the induction of apoptosis in TRAIL-sensitive cancer cells. When Ad-hTERT-DR4 infected TRAIL-resistant HCE4 cells and Ad-ILZ-TRAIL infected TRAIL-resistant HCE7 cells were co-cultured, cell deaths were evident 24 h after co-culture. Taken together, our results reveal that the combination of TRAIL and cancer cell-specific expression of DR4 has the potential to overcome the resistance of cancer cells to TRAIL without inducing significant cell death in normal cells.
Tumor Necrosis Factor-alpha/genetics/*pharmacology/secretion ; Telomerase/genetics ; TNF-Related Apoptosis-Inducing Ligand ; Receptors, Tumor Necrosis Factor/genetics/*metabolism ; Promoter Regions (Genetics) ; Neoplasms/genetics/metabolism/pathology ; Membrane Glycoproteins/genetics/*pharmacology/secretion ; Humans ; Drug Resistance, Neoplasm ; DNA-Binding Proteins/genetics ; Cell Line ; Apoptosis Regulatory Proteins/genetics/*pharmacology/secretion ; Apoptosis/*drug effects ; Antineoplastic Agents/*pharmacology ; Adenoviridae/genetics

For Korean dialysis patients, chronic kidney disease-mineral bone disorder is a serious burden because of cardiovascular calcification and mortality. However, recent epidemiologic data have demonstrated that many patients undergoing maintenance hemodialysis are out of the target ranges of serum calcium, phosphorus, and intact parathyroid hormone. Thus, we felt the necessity for the development of practical recommendations to treat abnormal serum phosphorus, calcium, and iPTH in dialysis patients. In this paper, we briefly comment on the measurement of serum calcium, phosphorus, iPTH, dialysate calcium concentration, dietary phosphorus restriction, use of phosphate binders, and medical and surgical options to correct secondary hyperparathyroidism. In particular, for the optimal management of secondary hyperparathyroidism, we suggest a simplified medication adjustment according to certain ranges of serum phosphorus and calcium. Large-scale, well-designed clinical studies are required to support our strategies to control chronic kidney disease-mineral bone disorder in this country. Based on such data, our practice guidelines could be established and better long-term outcomes should be anticipated in our dialysis patients.
Calcium ; Dialysis ; Humans ; Hyperparathyroidism, Secondary ; Kidney* ; Mortality ; Parathyroid Hormone ; Phosphorus ; Phosphorus, Dietary ; Renal Dialysis

BACKGROUND: When differential diagnosis is difficult in thyroid follicular lesions with overlapping histological features, the immunohistochemical staining can help confirm the diagnosis. We aimed to evaluate the effectiveness of rapid immunohistochemical stains of CD56 and cytokeratin 19 on frozen sections of thyroid follicular lesion and explore the possible gains and limitations of the practice. METHODS: Eighty-six nodules of 79 patients whose intraoperative frozen sections were selected as the control group, and 53 nodules of 48 patients whose intraoperative frozen sections were subject to rapid immunohistochemistry were selected as the study group. RESULTS: Five nodules (6%) in the control group were diagnosed as follicular neoplasm and six nodules (7%) were deferred. In the study group, six nodules (11%) were follicular neoplasm and none were deferred. Three nodules (4%) in the control group showed diagnostic discrepancy between the frozen and permanent diagnoses, but none in the study group. The average turnaround time for the frozen diagnosis of the control group was 24 minutes, whereas it was 54 minutes for the study group. CONCLUSIONS: Intraoperative rapid immunohistochemical stains significantly decreased the diagnostic discrepancy in this study. Considering the adverse effects of indefinite frozen diagnosis or discrepancy with permanent diagnoses, the intraoperative rapid immunohistochemical stain can help to accurately diagnose and hence provide guidance to surgical treatment.
Coloring Agents ; Diagnosis ; Diagnosis, Differential ; Frozen Sections ; Humans ; Immunohistochemistry ; Keratin-19 ; Thyroid Gland*

PURPOSE: Urinalysis is one of the best methods for early detection of renal disease and recent wide- spread use of mass screening led to increasing prevalence of asymptomatic urinary abnormalities. Usually, primary chronic glomerulonephritis first presents with asymptomatic urinary abnormalities and chronic glomerulonephritis commonly causes end-stage renal disease. However, clinical outcome of asymptomatic urinary abnormalities in adults is not well known. METHODS: Between Jan 1995 to Aug 2009, 333 patients with asymptomatic urinary abnormalities who underwent percutaneous renal biopsy were enrolled. A retrospective study was performed to clarify the prognostic factors and the long-term renal outcome of this disease. RESULTS: According to clinical manifestation, there were 79 (23.7%) of isolated microscopic hematuria, 30 (9.0%) of isolated proteinuria and 224 (67.3%) of mixed hematuria and proteinuria. The patients were significantly younger in case with microscopic hematuria. Group with microscopic hematuria had significantly shorter follow up period (p=0.013). In pathologic diagnosis, IgA nephropathy was most common with 244 patients (73.3%). The proteinuria group and mixed group showed significantly higher rate of progression to chronic renal failure than the microscopic hematuria group (p=0.015). The group that 24-hour proteinuria was more than 0.5 g/day showed significantly higher progression rate to chronic renal failure (p<0.000). Using univariate regression analysis, 3 risk factors for progression to chronic renal failure were identified: age, serum creatinine, 24-hour total urine protein. In multivariate regression analysis, only 24-hour proteinuria was the independent prognostic factor for progression to chronic renal failure. CONCLUSION: IgA nephropathy is the most common cause of asymptomatic urinary abnormalities in adults. The group of proteinuria has higher progression rate to chronic renal failure than other groups. Over 0.5 gm of 24-hour proteinuria is a significant risk factor for progression to chronic renal failure in multivariate regression analysis.
Adult ; Biopsy ; Creatinine ; Follow-Up Studies ; Glomerulonephritis ; Glomerulonephritis, IGA ; Hematuria ; Humans ; Kidney Failure, Chronic ; Mass Screening ; Prevalence ; Proteinuria ; Renal Insufficiency ; Retrospective Studies ; Risk Factors ; Urinalysis

A spontaneous subcapsular hematoma in an allograft kidney is a rare condition with only a few cases reported in the literature. Common causes of subcapsular hematoma of an allograft include trauma, post-biopsy status, occult malignancy, vascular diseases, and infection. Chronic allograft dysfunction related to spontaneous subcapsular hematoma is extremely rare. We report a case of spontaneous subcapsular hematoma in a patient who underwent a renal transplant 14 years ago in which we could not find an associated condition.
Hematoma ; Humans ; Kidney ; Transplantation, Homologous ; Transplants ; Vascular Diseases

Background/Aims: Lumican, a small leucine-rich proteoglycan, has shown osteoprotective effects by synchronously stimulating bone formation and suppressing bone resorption. To clarify the role of lumican in human bone metabolism, the association between lumican concentrations and osteoporosis-related phenotypes was evaluated using bone marrow (BM) samples directly reflecting local microenvironments. Methods: BM aspirates were obtained from 77 patients during hip surgery for either fragility hip fractures (HF) (n = 29) or osteoarthritis (n = 48) and centrifuged. Concentrations of lumican and biochemical bone markers in BM supernatants were measured using enzyme linked immunosorbent assays. Results: After considering confounders, lumican concentrations in BM supernatants were 16.9% lower in patients with HF than in controls, with each increase in the standard deviation of lumican concentration being associated with a 61% lower likelihood of HF. The odds ratios for HF decreased linearly with increasing lumican tertiles in BM, with the odds of having fragility HF markedly lower in participants in the highest than in the lowest lumican tertile. Higher lumican level correlated significantly with higher femur neck bone mineral density and higher bone-specific alkaline phosphatase levels, but not with tartrate-resistant acid phosphatase 5b concentrations, in BM supernatants. Conclusions These data clinically validate previous in vitro and animal experiments showing the beneficial roles of lumican for bone homeostasis and suggest that lumican may contribute to a reduction in fracture risk in humans mainly through its stimulation of bone formation.

Digital pathology is being gradually adopted in hospitals due to technological advances. We propose that digital pathology can be used in Mohs micrographic surgery (Mohs surgery) to precisely check residual tumor cells in frozen tumor margin tissues. This would aid surgeons and pathologists in accurately recording tumor margins and give patients the benefit of shorter operation time.

We describe herein histologic, immunohistochemical, and molecular findings and clinical manifestations of a rare case of an extremely well differentiated papillary thyroid carcinoma (EWD-PTC). Similarly, it is also difficult to diagnose follicular variant papillary thyroid carcinoma (FVPTC), whose diagnosis is still met with controversy. A recently reported entity of well-differentiated tumor of uncertain malignant potential (WDT-UMP) is added to the diagnostic spectrum harboring EWD-PTC and FVPTC. We report this case, because EWD-PTC is different from FVPTC in its papillary architecture, and also from WDT-UMP in its recurrence and metastatic pattern. These morphologically deceptive entities harbored diagnostic difficulties in the past because the diagnosis depended solely on histology. However, they are now diagnosed with more certainty by virtue of immunohistochemical and molecular studies. We experienced a case of EWD-PTC, which had been diagnosed as adenomatous hyperplasia 20 years ago and manifested recurrence with lymph node (LN) metastasis 7 years later. After another 7 years of follow-up, a new thyroid lesion had developed, diagnosed as FVPTC, with LN metastasis of EWD-PTC. One year later, the patient developed metastatic FVPTC in the skull. Immunohistochemically, the EWD-PTC was focally positive for CK19, negative for galectin-3, and focally negative for CD56. Molecular studies revealed BRAF-positivity and K-RAS negativity. The FVPTC in the left thyroid showed both BRAF and K-RAS negativity. In conclusion, EWD-PTC and FVPTC share similar histologic features, but they are different tumors with different molecular biologic and clinical manifestations. A large cohort of EWD-PTC should be included in further study.
Adenocarcinoma, Follicular/pathology/secondary ; Adult ; Carcinoma, Papillary, Follicular/pathology/*secondary ; Female ; Galectin 3/analysis ; Humans ; Hyperplasia/pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local/pathology ; Skull Neoplasms/*secondary ; Thyroid Neoplasms/*pathology

PURPOSE: Peritoneal dialysis (PD) catheter removal is regarded as an important index of patient morbidity. The aim of this study was to evaluate factors influencing catheter loss following peritonitis in PD patients. METHODS: We retrospectively reviewed 917 episodes of peritonitis in 621 new CAPD patients from Jan 2001 to Feb. 2009 in Dongsan Medical center. Episodes requiring PD catheter removal were compared by both univariate and multivariate analyses with those in which PD catheters were preserved. RESULTS: When peritonitis episodes requiring PD catheter removal (n=80) were compared to catheter preserved peritonitis episodes (n=837), the incidence of PD catheter loss increased as the duration on PD preceding the peritonitis were longer (p<0.000). Also, PD catheter removal was more likely to occur after peritonitis episodes with low serum albumin level (p=0.009) and high serum CRP level (p<0.000), those with long duration of PD effluent leukocyte count remaining above 100/mm3 (p<0.000), those with concomitant exit site/tunnel infection (p=0.043), and those with presence of abdominal pathology (p<0.000). The microbiological determinants of PD catheter loss included two or more bacteria cultured (p=0.002) and fungi (p<0.000). In multivariate analysis, the duration of PD effluent leukocyte count remaining above 100/mL and the number of organism cultured were independent risk factors of PD catheter removal in peritonitis episodes. CONCLUSION: Duration of PD effluent leukocyte count remaining above 100/mm3, and the number of organisms cultured were independent risk factors for catheter removal following peritonitis.
Bacteria ; Catheters ; Device Removal ; Fungi ; Humans ; Incidence ; Leukocyte Count ; Multivariate Analysis ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory ; Peritonitis ; Retrospective Studies ; Risk Factors ; Serum Albumin

Primary ovarian transitional cell carcinoma (TCC) is extremely rare type of tumor and resembles transitional cell carcinoma of the bladder. Primary ovarian TCC has been classified as a different subtype from malignant Brenner tumor for it's histologic and clinical characteristics. It usually presents at an advanced stage .Though more aggressive than malignant Brenner tumor, it shows more favorable prognosis because of better response to the chemotherapy than other epithelial ovarian carcinomas. We experienced a case of primary ovarian transitional cell carcinoma in a premenopausal woman who underwent staging operation and chemotherapeutic treatment, and herein report the case with a brief review of related literatures.
Brenner Tumor ; Carcinoma, Transitional Cell ; Female ; Humans ; Ovary ; Prognosis ; Urinary Bladder