PURPOSE: Idoxifene is currently entering phase II clinical trials for the treatment of advanced breast cancer. The radiolabeled idoxifene using 123I provides an opportunity for clinical pharmacology with single photon emission computed tomography (SPECT). The purpose of this study was to prepare radiolabeled idoxifene using 123I and to determine its cell uptake of breast cancer cell line. MATERIALS AND METHODS: With a view to evaluating new anticancer drugs, we are investigating the novel antiestrogen pyrrolidino- 4-iodotamoxifen (idoxifene). [123I]Idoxifene has been prepared in no-carrier-added form using a tributyl stannylated precursor which has been synthesized by means of (2-chloroethoxy)benzene with (+/-)-2- phenylbutanoic acid on the basis of previously reported standard methods. The biodistribution and dynamic behavior of the compound were investigated using the comparative breast cancer cell line, MCF-7 (estrogen receptor-positive) and MDA-MB-468 (non-estrogen receptor). RESULTS AND CONCLUSION: Acylation of (2-chloroethoxy)benzene with (+/-)-2-phenylbutanoic acid gave the versatile ketone (81%) which reacted with 1,4-diiodobenzene to give triphenylethylene as a mixture of E and Z geometric isomers, which were separated by the recrystallization in ethanol. The E-isomer was treated with pyrrolidine to give idoxifene (67%). In order to incorporate radioactive iodine into the 4-position, the 4-stannylated precursor was prepared (30%). The yield of radioiodination was 90-92% with a high radiochemical purity greater than 98%. The ratio of tumor uptake of the breast cancer cell line between MCF-7 and MDA-MB-468 was about 1.7.
Acylation ; Breast Neoplasms* ; Breast* ; Cell Line ; Estrogen Receptor Modulators ; Ethanol ; Iodine ; Pharmacology, Clinical ; Tomography, Emission-Computed, Single-Photon

The present study was firstly undertaken in an attempt to compare simultaneously EMG(electromyography) and two new ACC(accelerography) reponses in the both hand following vecuronium administration in 26 ASA 1 or 2 adult patients undergoing general anesthesia. In the three NMT monitors, stimulating electrodes are applied similarly over the ulnar nerve on the volar side of the wrist, but the evoked EMG(Relaxograph, Datex Co.) responses obtained from the hypothenar muscles, TOFGUARD(Biometer Co.) responses from adductor pollicis and ParaGraph(Utah Med. Prod. Co.) responses from both muscles of hypothenar and thenar muscle of the hand respectively. Following induction of anesthesia with thiopental sodium(5 mg/kg) and vecuronium(0.08 mg/kg) intravenously, endotracheal intubation was facilitated and anesthesia was maintained with a mixture of enflurane(1~2%) and N2O(50%) . After loss of consciousness, the assessment of the neuromuscular blockade was started. We compared simultaneously TR(train-of-four ratio) responses of EMG at the one hand, and two new ACC named TOF-GUARD and ParaGraph at the other hand respectively during evoked recovery from vecuronium induced neuromuscular blockade. The result was the greater depression of TR response in TOF-GUARD and the lesser depression of TR response in ParaGraph than those in EMG. But test for parallelism did not show a statistically significant difference between the slope of these regression lines. Conclusively, the regression line for TR seems to be tend to give an impression that two new ACC named TOF-GUARD and ParaGraph would be suitable in the assessment of neuromuscular blockade in clinical anesthesia.
Adult ; Anesthesia ; Anesthesia, General ; Cytochrome P-450 CYP2B1 ; Depression ; Electrodes ; Hand ; Humans ; Intubation, Intratracheal ; Muscles ; Neuromuscular Blockade ; Thiopental ; Ulnar Nerve ; Unconsciousness ; Vecuronium Bromide* ; Wrist

Phagocytosis of serum- and IgG-opsonized zymosan (SOZ and IOZ, respectively) particles into J774A.1 macrophages induced apoptosis of the cells, accompanied by the expression of p21(WAF1), one of cyclin-dependent protein kinase (CDK) inhibitors. Furthermore, phagocytosis of SOZ and IOZ particles into macophages induced superoxide formation. Tat-superoxide dismutase (SOD), which is readily transduced into the cells using Tat-domain, protected the cells from the apoptosis induced by phagocytosis of SOZ and IOZ particles. lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma) also caused the apoptosis of the cells. However, Tat-SOD could not protect the cells from LPS/IFN-gamma induced apoptosis, suggesting that apoptosis mechanisms involved are different from each other. In the present study, we determined the amounts of nitric oxide (NO) produced by SOZ, IOZ, and LPS/IFN-gamma, and found that SOZ and IOZ did not induce the generation of NO in macrophages, whereas LPS/ IFN-gamma did. The apoptosis due to phagocytosis was accompanied with the release of cytochrome c from mitochondrial membrane to cytosolic fraction. Furthermore, SOZ and IOZ induced the cleavage of procasapase-3 (35 kDa) to give rise to an active caspase-3 (20 kDa), which was blocked by Tat- SOD but not by 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), a scavenger of NO. On the other hand, LPS/IFN-gamma caused the activation of procaspase-3, which was blocked by PTIO but not by Tat-SOD. Taken together, phagocytosis of SOZ and IOZ particles induced apoptosis through superoxide but not NO in macrophages, accompanied with the release of cytochrome c and the activation of caspase-3.
Apoptosis/*immunology ; Caspases/metabolism ; Cell Line ; Cyclins/biosynthesis ; Cytochromes c/metabolism ; Immunoglobulin G/*immunology ; Interferon Type II/pharmacology ; Lipopolysaccharides/pharmacology ; Macrophages/*immunology/metabolism ; Nitric Oxide/*metabolism ; Opsonins/immunology ; Phagocytosis/*physiology ; Superoxide Dismutase/metabolism ; Superoxides/*metabolism ; Zymosan

PURPOSE: This study aimed to assess whether a young age at the time of diagnosis with osteosarcoma has value to predict the prognosis. MATERIALS AND METHODS: Sixty-seven children with stage II osteosarcoma were stratified according to the age of 10. There were 32 preadolescents (< or =10 years) and 35 adolescents (10 < age < or = 15 years). The patients were analyzed for their clinical characteristics, the histologic response to preoperative chemotherapy, event-free survival (EFS) and the patterns of relapse. RESULTS: After a median follow-up of 54 months (range: 6~153 months), the 5-year EFS of the preadolescent and adolescent groups was 64.5+/-9.3% and 58.2+/-9.1%, respectively, and age did not have any statistical significance for survival (p=0.55). Cox regression analysis revealed that both the serum level of alkaline phosphatase and the histologic response to preoperative chemotherapy were significantly related to survival of the 67 patients. Those patients aged less than 7 years responded poorly to preoperative chemotherapy and their rate of amputation was 43%. However, their 5-year EFS was not statistically different from the older patients (57.1+/-18.7 vs 67.7+/-6.3%, respectively, p=0.58). CONCLUSIONS: We could not find any statistical difference in the clinical characteristics and survival from osteosarcoma for the preadolescents and adolescents, so the current approach of having the same protocol for both groups of patients seems to be reasonable.
Adolescent ; Alkaline Phosphatase ; Amputation ; Child* ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Osteosarcoma* ; Prognosis ; Recurrence ; Retrospective Studies*

The aim of this study was to evaluate the incidence of and risk factors for the development of diabetic retinopathy (DR) and progression to proliferative DR (PDR) in Korean patients. Patients diagnosed with type 2 diabetes and followed for more than 5 years at a university-based clinic since 2000 were consecutively enrolled in this retrospective cohort study. Based on the DR classification at the initial and final visits, the incidence and progression of DR was determined and patient characteristics were compared according to DR progression. Hazard ratios of each putative risk factor for DR progression were calculated with a multivariate Cox proportional hazard model. Rate of DR development and progression to PDR were 32.1/1,000 and 26.2/1,000 person-years, respectively. A longer duration of diabetes and higher mean HbA1c level were significant risk factors for the development of DR. Regarding progression to PDR, higher mean HbA1c level, higher standard deviation of HbA1c, and higher urine albumin-to-creatinine ratio were significant risk factors. The rates of development of DR and progression to PDR in Koreans with type 2 diabetes are lower than those reported over the last decade. An inadequate blood glycemic control is the common risk factor for development and progression of DR.
Adult ; Aged ; Causality ; Comorbidity ; Diabetes Mellitus, Type 2/*epidemiology ; Diabetic Retinopathy/*epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Republic of Korea/epidemiology ; Risk Factors ; Socioeconomic Factors ; Tertiary Care Centers/*statistics & numerical data

OBJECTIVE: Although the detection of crossed cerebellar diaschisis (CCD) by means of different imaging modalities is well described, little is known about its diagnosis by computed tomography perfusion (CTP) imaging. We investigated the detection rate of CCD by CTP imaging and the factors related to CCD on CTP images in patients with acute ischemic stroke. MATERIALS AND METHODS: CT perfusion maps of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time-to-peak (TTP) obtained from 81 consecutive patients affected by an acute ischemic stroke were retrospectively reviewed. Whole-brain perfusion maps were obtained with a multichannel CT scanner using the toggling-table technique. The criteria for CCD was a unilateral supratentorial ischemic lesion and an accompanying decrease in perfusion of the contralateral cerebellar hemisphere on the basis of CTP maps by visual inspection without a set threshold. Maps were quantitatively analyzed in CCD positive cases. RESULTS: The criteria for CCD were fulfilled in 25 of the 81 cases (31%). Detection rates per CTP map were as follows: MTT (31%) > TTP (21%) > CBF (9%) > CBV (6%). Supratentorial ischemic volume, degree of perfusion reduction, and infratentorial asymmetry index correlated strongly (R, 0.555-0.870) and significantly (p < 0.05) with each other in CCD-positive cases. CONCLUSION: It is possible to detect CCD on all four of the CTP-based maps. Of these maps, MTT is most sensitive in detecting CCD. Our data indicate that CTP imaging is a valid tool for the diagnosis of CCD in patients affected by an acute hemispheric stroke.
Aged ; Blood Flow Velocity ; Cerebellar Diseases/*radiography ; Cerebral Angiography/*methods ; Cerebrovascular Circulation ; Contrast Media/diagnostic use ; Female ; Humans ; Iohexol/diagnostic use ; Magnetic Resonance Imaging ; Male ; Radiographic Image Interpretation, Computer-Assisted ; Retrospective Studies ; Stroke/*radiography ; Tomography, X-Ray Computed/*methods

OBJECTIVES: Due to the heterogeneous receptor distribution and changes of receptor status over time, the biochemical measurement of estrogen receptor status of biopsy specimens is not sufficient to diagnose breast cancer. As a result, I-123 labeled estradiols have been applied for the diagnosis. The purpose of this study was to develop a suitable radioligand for imaging estrogen receptor-positive human breast tumors. METHODS: Among the various estradiol derivatives, 17alpha-[123I]iodovinyl estradiol ([123I]IVE) has been prepared from 17alpha-ethynyl estradiol. Labeling of E-17alpha-[123I]iodovinyl estradiol (E-[123I]IVE) was carried out using peracetic acid with [123I]NaI and Z-[123I]IVE labelling was archived using chloamine- T/HCl solution with [123I]NaI. Labeling yield was determined by silica thin-layer chromatography (TLC) and radiochemical purity was measured by high performance liquid chromatography (HPLC). The biodistribution of E-[123I]IVE was measured in immature female rats at 60 min, 120 min and 300 min after injection. RESULTS: The labeling yield of two isomers was 92% and 94% (E-[123I]IVE and Z-[123I]IVE, respectively). The radiochemical purity was more than 98% after purification. The highest uptake was observed at 120 min in uterus (3.11% ID/g for E-[123I]IVE). CONCLUSION: These results suggest the possibility of using E-[123I]IVE as an imaging agent for the evaluation of the presence of estrogen receptor in patients with breast cancer.
Animals ; Biopsy ; Breast Neoplasms ; Chromatography, Liquid ; Chromatography, Thin Layer ; Diagnosis ; Estradiol* ; Estrogens ; Female ; Humans ; Peracetic Acid ; Rats ; Silicon Dioxide ; Uterus

PURPOSE: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Although survival rate of osteosarcoma patients has markedly improved, about 20-30% of patients still have a relapse. This study was aimed to find factors that influence postrelapse survival of osteosarcoma in childhood and adolescents. METHODS: Between 1985 and 2004, of 461 patients who were diagnosed and treated as osteosarcoma in Korean Cancer Center Hospital, 180 patients with recurrent osteosarcoma were retrospectively reviewed. We examined survival rates and analyzed prognostic factors, such as relapse site, post-relapse treatment methods, pathologic response to neoadjuvnat chemotherapy, metastasis at first diagnosis, and relapse free interval. RESULTS: The overall recurrence rate of patients with osteosarcoma was 39%. The 5-year and 10-year postrelapse survival rates in the recurrent osteosarcoma were 13% and 4%, respectively. The 5-year post-relapse survival rate was influenced by site of relapse (lung, 39%; local, 0%; lung & bone, 25%; others, 12%; P<0.05), relapse-free interval (<12 months, 13%; > or =12 months, 44%, P<0.05), and post-relapse treatment methods (with surgery, 38%; without surgery, 11%; P<0.05). CONCLUSION: The survival rate of recurrent case is very low after 10 years, so new second-line chemotherapy and active treatment is needed to increase survival. Aggressive surgery with the removal of recurrence sites combined with multi-agent chemotherapy could either cure patients with recurrent osteosarcoma or significantly prolong their survival.
Adolescent ; Child ; Humans ; Korea ; Lung ; Neoplasm Metastasis ; Osteosarcoma ; Recurrence ; Retrospective Studies ; Survival Rate

PURPOSE: Features of epidermal growth factor receptor (EGFR) expression in osteosarcoma and in vitro efficacies of EGFR inhibitors against osteosarcoma cells were evaluated. MATERIALS AND METHODS: Thirty biopsy samples of osteosarcoma patients were retrospectively analyzed for EGFR protein expression by immunohistochemistry. Relationships between EGFR expression and clinicopathologic characteristics and treatment outcomes were evaluated. Four osteosarcoma cell lines were analyzed for EGFR and p-EGFR expression by western blotting. Efficacies of gefitinib and BIBW2992 on osteosarcoma cells were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tyrosine kinase domains in exons 18 to 21 were sequenced and gene expression analyses of EGFR and PTEN were performed in four osteosarcoma cell lines. RESULTS: EGFR protein was expressed in 27 (90%) samples (6 low, 12 intermediate, 9 high) and in three cell lines. Intermediate or high staining for EGFR was related to a tumor volume<150 mL (p<0.001) and histologic subtype other than osteoblastic type (p=0.03). However, EGFR expression was not associated with histologic response to preoperative chemotherapy or survival. Gefitinib and BIBW 2992 did not have any significant inhibitory effect on cell viabilities. DNA sequencing analysis revealed three osteosarcoma cell lines have single base changes at codon 2361 of exon 20 (G to A), without affecting translation results. Furthermore, no mutation was found to be associated with constitutive EGFR activation. CONCLUSION: In the present study, gefitinib and BIBW2992 were not effective against osteosarcoma cells. However, as osteosarcoma cells express EGFR, further studies are necessary to explore the potential of other therapeutic agents targeting EGFR.
Biopsy ; Blotting, Western ; Cell Line ; Cell Survival ; Codon ; Epidermal Growth Factor ; Exons ; Gene Expression ; Humans ; Immunohistochemistry ; Osteoblasts ; Osteosarcoma ; Protein-Tyrosine Kinases ; Quinazolines ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Sequence Analysis, DNA ; Tetrazolium Salts ; Thiazoles

A 57-year-old woman who had a history of diabetes was admitted due to fever and left flank pain. Acute pyelonephritis was diagnosed by clinical findings including left costovertebral area tenderness, positive urine and blood cultures. Subsequent abdominal computed tomography demonstrated multiple abscess pockets in the left renal parenchyme and ipsilateral renal vein thrombosis. She was fully recovered after treatment with antibiotics, low-molecular weight heparin and low-dose aspirin for six weeks. Our case emphasizes that renal vein thrombosis could be complicated in acute pyelonephritis, especially in patients with diabetes. It is reasonable to speculate that factors such as hemoconcentration caused by fever and osmotic diuresis and compression of renal vascular pedicle by renal abscess might have had a role in inciting the renal vein thrombosis.
Abscess ; Anti-Bacterial Agents ; Aspirin ; Diuresis ; Female ; Fever ; Flank Pain ; Heparin ; Humans ; Middle Aged ; Pyelonephritis* ; Renal Veins* ; Thrombosis*