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1.
Osteoporos Int ; 30(1): 145-153, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30361752

ABSTRACT

There is ongoing effort to discharge patients early after hip fracture surgery to reduce the medical and economic burden. We tried to find whether there is any related side effect, and discovered that early discharge, especially before 10 days after surgery, is associated with higher mortality. INTRODUCTION: The aim of this study was to analyze the association between the length of hospital stay after hip fracture and 1-year mortality in older adults aged ≥ 65 years old. METHODS: We conducted a retrospective cohort study using the Korean National Health Insurance Service data to identify patients who were discharged after hip fracture surgery from 2007 to 2009 among 487,460 older adults of age ≥ 65 years. The lengths of stay involving hip fracture surgery were categorized at 10-day interval, and analyzed in relation to 1-year mortality from the date of hospital discharge. RESULTS: A total of 4213 patients were discharged after hip fracture surgery, of whom 604 (14.3%) died within 1 year of discharge. The average length of stay was 30.7 days (standard deviation 24.5 days). The 1-year mortality was the highest for the length of stay ≤ 10 days group at 21.7%, followed by 15.2%, 14.3%, 13.3%, and 12.4% for > 40, 21-30, 31-40, and 11-20 days groups, respectively (p value 0.05). On Cox proportional hazard regression, the adjusted hazard ratio for length of stay ≤ 10 days group was 1.56 (95% confidence interval 1.14-2.12) against the reference group (11-20 days), while other groups did not show statistical significance. Higher risk of death was associated with increasing age, male gender, Charlson comorbidity index ≥3, subtrochanteric fracture, and discharge to tertiary care hospitals and long-term care hospitals. CONCLUSION: Older adults discharged within 10 days of hospital admission for hip fracture surgery have higher 1-year mortality after discharge.


Subject(s)
Hip Fractures/mortality , Hip Fractures/surgery , Length of Stay/statistics & numerical data , Osteoporotic Fractures/mortality , Osteoporotic Fractures/surgery , Age Distribution , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip/mortality , Arthroplasty, Replacement, Hip/statistics & numerical data , Databases, Factual , Female , Fracture Fixation, Internal/methods , Fracture Fixation, Internal/mortality , Fracture Fixation, Internal/statistics & numerical data , Hospitalization , Humans , Kaplan-Meier Estimate , Male , Patient Discharge , Republic of Korea/epidemiology , Retrospective Studies , Sex Distribution , Social Class
3.
Cytopathology ; 28(1): 65-73, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27245883

ABSTRACT

OBJECTIVE: According to the Bethesda System for Reporting Thyroid Cytopathology, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is a heterogeneous category that includes cases with architectural and/or nuclear atypia insufficient to warrant classification as malignant neoplasms. The ambiguous and descriptive characteristics of the AUS/FLUS category mean that the impact of the present guidelines on repeat fine needle aspiration (FNA) is unclear. The present study reclassified AUS/FLUS cases into four sub-categories and then correlated them with histological or cytological follow-up data to clarify the risk of malignancy. METHODS: Ninety-four cases of AUS/FLUS with available follow-up data were reviewed and assigned to one of four sub-categories: (i) AUS-N (nuclear atypia); (ii) AUS-A (architectural atypia); (iii) AUS-O (predominant oncocytic changes); and (iv) AUS-N/A (both nuclear and architectural atypia). The four sub-categories were correlated with subsequent histological or cytological follow-up data, including core needle biopsy, resection, or repeat FNA. RESULTS: Malignancy was identified in 34 of 94 cases (36.2%). The upper limit estimate for malignancy was 43.6%, and the lower limit estimate was speculated as 9.8%. The malignancy rate was highest in cases within the AUS-N sub-category (65.8%, range 16.6%-78.1%). CONCLUSIONS: The present study suggests that cases in the AUS/FLUS category have a higher risk of malignancy than previously thought. Because of the heterogeneous nature of the AUS/FLUS category, further sub-classification might be more effective in achieving appropriate risk stratification and better clinical management.


Subject(s)
Cytodiagnosis , Thyroid Gland/pathology , Thyroid Neoplasms/diagnosis , Thyroid Nodule/diagnosis , Adult , Aged , Biopsy, Fine-Needle , Female , Humans , Male , Middle Aged , Risk Factors , Thyroid Neoplasms/classification , Thyroid Neoplasms/pathology , Thyroid Nodule/classification , Thyroid Nodule/pathology
4.
Br J Surg ; 103(8): 1020-5, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27121346

ABSTRACT

BACKGROUND: This study evaluated the impact of lymph node-related factors on the risk of and site of recurrence in patients who had papillary thyroid carcinoma with lymph node metastasis in the lateral compartment (classified as pN1b). METHODS: Patients underwent total thyroidectomy with unilateral modified radical neck dissection for classical papillary thyroid carcinoma. Risk factors for recurrence were evaluated according to the pattern of recurrence. RESULTS: A total of 324 patients were included in the study. The median follow-up was 63 (range 14-181) months. Recurrence was detected in 47 patients (14·5 per cent). In the multivariable analysis, a maximum diameter of metastatic lymph nodes larger than 2·0 cm (hazard ratio (HR) 1·15, 95 per cent c.i. 1·06 to 1·25; P = 0·033) and a central compartment metastatic lymph node ratio of more than 0·42 (HR 3·35, 1·65 to 6·79; P < 0·001) were identified as independent risk factors for locoregional recurrence. Age 45 years or older (HR 5·69, 1·24 to 26·12; P = 0·025) and extranodal extension of metastasis (HR 12·71, 1·64 to 98·25; P = 0·015) were risk factors for distant metastasis. In subgroup analysis of locoregional recurrence, several lymph node-related factors affected the risk of recurrence according to the specific site of metastasis. CONCLUSION: Lymph node-related factors are of importance for the risk of recurrence in patients with classical papillary thyroid carcinoma classified as pN1b.


Subject(s)
Carcinoma, Papillary/pathology , Neck Dissection , Neoplasm Recurrence, Local/pathology , Thyroid Neoplasms/pathology , Age Factors , Carcinoma, Papillary/surgery , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Metastasis , Retrospective Studies , Risk Factors , Thyroid Neoplasms/surgery , Thyroidectomy
5.
Clin Radiol ; 70(1): 42-7, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25443776

ABSTRACT

AIM: To evaluate recurrence rate and associated risk factors for recurrence after ethanol ablation (EA) in patients with predominantly cystic thyroid nodules. MATERIALS AND METHODS: This observational study was approved by the Ethics Committee of the Institutional Review Board and informed consent for procedures was obtained. From April 2009 to April 2013, 107 consecutive patients with predominantly cystic nodules were treated using EA. Recurrence was defined as nodules showing a residual solid portion with internal vascularity, cosmetic problems remaining, or persistent symptoms, and patients who requested additional therapy to resolve their symptomatic or cosmetic problems. Delayed recurrence was defined as treated nodules that showed no recurrent features at 1 month, but showed newly developed recurrent features during the longer follow-up period. Multivariate analysis was used for variables to demonstrate the independent factors related to volume reduction. RESULTS: One month after EA, 18.7% of patients (20/107) showed recurrence. Among 87 patients with non-recurrence, 24.1% (21/87) showed delayed recurrence. The total recurrence rate was 38.3% (41/107). Patients with recurrence (n = 41) were treated using radiofrequency ablation (n = 28), second EA (n = 4), and refused further treatment (n = 9). These patients responded well to repeat EA and radiofrequency ablation. Multivariate analysis demonstrated that the initial nodule volume (>20 ml; p < 0.036) and vascularity (grade >1; p < 0.049) were independent predictors of volume reduction at last follow-up. CONCLUSIONS: The results revealed that although EA seemed to be effective during the initial period, delayed recurrence should be considered during longer-term follow-up. The independent predictors of recurrence were initial volume (>20 ml) and vascularity.


Subject(s)
Cysts/therapy , Neoplasm Recurrence, Local/epidemiology , Thyroid Nodule/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Catheter Ablation/methods , Child , Cysts/diagnostic imaging , Ethanol/therapeutic use , Female , Humans , Male , Middle Aged , Risk Factors , Thyroid Nodule/diagnostic imaging , Treatment Outcome , Ultrasonography, Interventional/methods , Young Adult
6.
Transplant Proc ; 46(2): 637-9, 2014.
Article in English | MEDLINE | ID: mdl-24656033

ABSTRACT

BACKGROUND: Renal transplantation is the best treatment for patients with end-stage renal disease. Although there is significantly increased risk of malignancy after renal transplantation, carcinoma of the native kidney is very rare, and moreover, the risk of endocrinologic malignancy after renal transplantation is lower than in the general population and adrenal cortical carcinoma extremely rare. We report a case of incidental renal cell carcinoma originating from a native kidney after en-bloc resection for adrenal carcinoma in a kidney transplant recipient. CASE REPORT: A 57 year-old male patient had undergone living-donor kidney transplantation for chronic renal failure from hypertension 15 years earlier and had a right adrenal tumor diagnosed on surveillance abdomen-pelvis computerized tomography. Based on 24-hour catecholamine laboratory findings, nonfunctioning tumor was suspected. The planned en-bloc resection of right adrenal gland and right native kidney combining the perirenal tissue and Gerota fascia was performed, because the tumor was suspicious for malignancy and could possibly invade the perirenal tissue or right kidney. On the final pathology, combined adrenal cortical carcinoma and incidental renal cell carcinoma was confirmed. Renal cell carcinoma was papillary, type I, and stage T1N0M0. Adrenal cortical carcinoma was 7.6 × 6.5 cm in size, had marked nuclear atypia, and was grade IV/IV. Mitotic counts were >10 per high-power field, but it had no capsular invasion or vascular invasion, and free resection margin was confirmed. In the preoperative period, he had taken immunosuppressants FK506 and mycophenolate sodium, but after combined carcinomas were confirmed, the regimen of combination of immunosuppressants was changed to sirolimus with low-dose FK506 and half-dose mycophenolate sodium.


Subject(s)
Adrenal Cortex Neoplasms/surgery , Carcinoma, Renal Cell/diagnosis , Incidental Findings , Kidney Neoplasms/diagnosis , Kidney Transplantation , Neoplasms, Second Primary/diagnosis , Humans , Male , Middle Aged
7.
AJNR Am J Neuroradiol ; 35(3): 582-6, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23969340

ABSTRACT

SUMMARY: Predominantly cystic thyroid nodules are often aspirated before radiofrequency ablation to enhance its efficacy; however internal bleeding during the aspiration is a problem. We evaluated the feasibility and safety of ethanol ablation to control internal bleeding that occurred during preparatory aspiration. Between September 2010 and August 2011, 11 of 40 predominantly cystic nodules bled internally during fluid aspiration before radiofrequency ablation. To control the bleeding, 99% ethanol was injected. The efficacy of ethanol in controlling bleeding, final nodule volume and complications were assessed. Control of the bleeding by ethanol ablation and subsequent radiofrequency ablation was feasible in all patients. Ninety-one percent (10/11) could be treated in 1 session. The mean nodule volume dropped from 17.1 to 4.3 mL (P < .018). There were no major complications. Ethanol ablation and radiofrequency ablation combination therapy is a feasible and safe technique for treating predominantly cystic thyroid nodules that exhibit internal bleeding during preparatory aspiration.


Subject(s)
Catheter Ablation , Ethanol/therapeutic use , Thyroid Nodule/therapy , Adult , Aged , Combined Modality Therapy , Feasibility Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Thyroid Nodule/pathology
8.
J Endocrinol Invest ; 35(4): 413-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21897114

ABSTRACT

BACKGROUNDS: Signal transducer and activators of transcription-3 (STAT3) plays a critical role in promoting survival and cell growth as well as facilitating angiogenesis and metastasis in several cancers. AIM: This investigation focused on evaluation of STAT3 activities in human papillary thyroid cancers (PTC). METHODS: STAT3 activities of nuclear extracts of tumor tissue were measured from 35 PTC patients using enzyme- linked immunosorbent assay-based kits. RESULTS: STAT3 activities of PTC tissues were significantly lower than those of surrounding normal thyroid tissues [0.36 (interquartile range 0.24-0.72) vs 0.50 (0.29-1.11) arbitrary units, p<0.01]. We further analyzed the association between STAT3 activity and clinicopathologic factors in PTC tissue. Tumors with size ≥2 cm displayed significantly lower STAT3 activities than those <2 cm [0.25 (0.21-0.37) vs 0.53 (0.37-0.61) arbitrary units, p<0.01]. Notably, tumor size was inversely correlated with STAT3 activities in T1799A BRAF mutation-positive cases (Rs=-0.58, p<0.05), but not mutation-negative cases. CONCLUSIONS: STAT3 activities of PTC measured via DNA binding are suppressed in contrast to other human cancers. Tumor size larger than 2 cm is the only clinicopathologic parameter associated with low STAT3 activity. Moreover, tumor size appears inversely correlated with STAT3 activity, specifically in T1799A BRAF mutation-positive cases.


Subject(s)
Carcinoma/metabolism , Carcinoma/pathology , STAT3 Transcription Factor/metabolism , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Adolescent , Adult , Aged , Carcinoma/genetics , Carcinoma, Papillary , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Female , Humans , Male , Middle Aged , Mutation/genetics , STAT3 Transcription Factor/genetics , Thyroid Cancer, Papillary , Thyroid Neoplasms/genetics , Young Adult
9.
Transplant Proc ; 43(6): 2428-30, 2011.
Article in English | MEDLINE | ID: mdl-21839284

ABSTRACT

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a rare complication with a high mortality rate after organ transplantation. Early antifungal therapy improves survival. In some cases, surgical resection is necessary for a complete remission. We have reported herein a case of sustained (but stationary) IPA cured by the modulation of immunosuppression with discontinuation of antifungal therapy. CASE: A 34-year-old man underwent liver transplantation experiencing are early bile leak and an acute rejection episode. Steroid pulse therapy was accompanied by intensified immunosuppression. After a week he developed intermittent hemoptysis, which was treated with antibiotics due to a diagnosis of pneumonia by chest X ray. Meanwhile the bile leak progressed to a huge biloma at reoperation 3 weeks after the initial operation he was converted from a choledochocholedochostomy to a hepaticojejunostomy. After 1 week, follow-up chest X ray showed the lesion had progressed to form an abscess. Subsequent chest computed tomography (CT) detected a pulmonary mass with internal necrosis and CT-guided lung biopsy revealed Aspergillus fumigatus on isolation. Antifungal therapy with voriconazole and/or amphotericin B for 3 months stopped disease progression but the lesion was sustained. We stopped antifungal therapy due to side effects and reduced the intensity of immunosuppression. Follow-up chest CT 5 months later showed improvement with a persistent cavitary lesion containing a fungal ball. However, after 9 months, there was no focal lesion in either lung. This unusual case of IPA was cured by reducing immunosuppression without antifungal therapy. CONCLUSION: IPA should be eradicated with prompt antifugal therapy, but stationary IPA can be observed cautiously while reducing immunosuppression.


Subject(s)
Antifungal Agents/therapeutic use , Immunosuppressive Agents/administration & dosage , Invasive Pulmonary Aspergillosis/drug therapy , Liver Transplantation/adverse effects , Living Donors , Adult , Antifungal Agents/adverse effects , Drug Therapy, Combination , Humans , Invasive Pulmonary Aspergillosis/diagnostic imaging , Invasive Pulmonary Aspergillosis/microbiology , Male , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/analogs & derivatives , Steroids/administration & dosage , Tacrolimus/administration & dosage , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
10.
Scand J Surg ; 100(2): 92-8, 2011.
Article in English | MEDLINE | ID: mdl-21737384

ABSTRACT

BACKGROUND AND AIMS: The prognosis for patients with ampulla of Vater cancer is better than other periampullary cancers. The aim of the present study is to determine the clinicopathologic factors predictive of survival and recurrence in patients with ampulla of Vater cancer. MATERIAL AND METHODS: From 1991 to 2008, we identified and reviewed 78 patients with ampulla of Vater cancer retrospectively. Clinicopathologic factors possibly influencing survival and recurrence were statistically analyzed. RESULTS: Pancreaticoduodenectomy was performed in 68 patients and 2 patients underwent transduodenal ampullectomy. Hospital mortality was 2.6%. The 5-year survival rates following resection were 59.9%. Univariate analysis for overall survival revealed that total bilirubin greater than 5 mg/dl, ulcerative tumors, differentiation, and pancreatic invasion were significant prognostic factors. Recurrence occurred in 31 patients. Univariate analysis for disease-free survival revealed that total bilirubin greater than 5mg/dl, preoperative biliary drainage, tumor differentiation, and stage were statistically significant. Multivariate analysis revealed that tumor differentiation was an independent prognostic factor for recurrence. The presence of lymph node metastasis did not affect overall survival significantly in this study. However, two or more metastatic lymph nodes significantly affect disease-free survival. CONCLUSIONS: Pancreaticoduodenectomy is a safe surgical procedure with acceptable long-term survival for ampulla of Vater cancer. Pancreaticoduodenectomy with lymph node dissection might control lymph node spread and enhance survival outcome.


Subject(s)
Ampulla of Vater/surgery , Common Bile Duct Neoplasms/surgery , Pancreaticoduodenectomy , Adult , Aged , Aged, 80 and over , Bilirubin/metabolism , Biomarkers/metabolism , Common Bile Duct Neoplasms/metabolism , Common Bile Duct Neoplasms/mortality , Common Bile Duct Neoplasms/pathology , Disease-Free Survival , Female , Hospital Mortality , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local , Pancreaticoduodenectomy/statistics & numerical data , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome
11.
Hernia ; 13(4): 431-4, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19085039

ABSTRACT

We report the case of a successful vaginal delivery following laparoscopic abdominal wall reconstruction in an adult survivor of an omphalocele without prior surgical repair. Untreated omphaloceles are rare in adulthood. A 30-year-old female patient presented with a large anterior abdominal wall defect due to an untreated omphalocele, who expressed a desire to have a baby in the near future. A laparoscopic herniorrhaphy was performed with a double-layered expanded polytetrafluoroethylene (ePTFE, Gore-Tex) mesh. The patient delivered a full-term healthy baby vaginally 2 years after surgical repair of the omphalocele.


Subject(s)
Abdominal Wall/surgery , Hernia, Umbilical/surgery , Plastic Surgery Procedures/methods , Pregnancy Outcome , Surgical Mesh , Adult , Delivery, Obstetric/methods , Female , Hernia, Umbilical/diagnosis , Humans , Infant, Newborn , Laparoscopy/methods , Pregnancy , Survivors , Tensile Strength , Vagina
12.
Nanotechnology ; 19(47): 475703, 2008 Nov 26.
Article in English | MEDLINE | ID: mdl-21836284

ABSTRACT

A new and simple method for the fabrication of densely packed magnetic nanodot arrays was developed using conventional sputtering deposition at room temperature. An anodized alumina template was employed for the formation of nanodot assemblies, consisting of carbon nanotubes (CNTs) and magnetic nanodot arrays. Each nanodot was formed exactly on top of a CNT and was arranged with a well-ordered structure in a wide range of area. It was also found that the size of dots and the distance between dots can be tailored by changing the length of CNTs, inducing a change of strength of dipolar interaction between nanodots.

13.
Scand J Clin Lab Invest ; 67(2): 207-14, 2007.
Article in English | MEDLINE | ID: mdl-17366000

ABSTRACT

OBJECTIVE: Laparoscopic surgery is thought to reduce the postoperative immunologic effects of surgical trauma. The aim of this study is to evaluate the influence of surgical trauma on systemic inflammation and the immune response in acute cholecystitis. MATERIAL AND METHODS: Thirty-three patients with acute calculous cholecystitis were assigned to laparoscopic cholecystectomy (LC, n=18) or open cholecystectomy (OC, n=15). Blood samples were obtained preoperatively and on postoperative day 1 (24 h after surgery) and day 3 (72 h after surgery), and blood concentration of C-reactive protein (CRP), leukocyte subpopulations, as well as levels of tumor necrosis factor-alpha (TNF-alpha) ex vivo secretion by peripheral blood mononuclear cells (PBMCs) were measured in both groups. RESULTS: Hospitalization was significantly shorter in the LC group than in the OC group (LC group: 3.7+/-1.2 days versus OC group: 6.3+/-2.7 days, p=0.010). There was no postoperative morbidity in the LC group, but two patients in the OC group had postoperative complications. Postoperative TNF-alpha ex vivo secretion by PBMCs and PBMC counts in the OC group were significantly lower than those in the LC group (p=0.002). The CRP level declined by postoperative day 3, but was significantly less in the OC group than in the LC group (p<0.001). Postoperative monocyte counts significantly decreased in the OC group compared with those in the LC group (p=0.001). CONCLUSIONS: A laparoscopic approach appears to cause less surgical trauma and immunosuppression than open surgery in patients with acute cholecystitis.


Subject(s)
Cholecystectomy, Laparoscopic/methods , Cholecystitis, Acute/surgery , Immunosuppression Therapy , Minimally Invasive Surgical Procedures , Cholecystectomy, Laparoscopic/adverse effects , Cholecystitis, Acute/immunology , Cholecystitis, Acute/physiopathology , Female , Humans , Length of Stay , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Minimally Invasive Surgical Procedures/adverse effects , Postoperative Complications/etiology , Postoperative Complications/immunology , Tumor Necrosis Factor-alpha/metabolism
15.
Gene Ther ; 13(14): 1110-7, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16525482

ABSTRACT

Despite recent advances in the chemotherapy of chronic hepatitis B (CHB), an effective viral suppression after cessation of therapy has not yet been achieved. To investigate whether hepatitis B virus (HBV)-specific T-cell responses are inducible and can contribute to the viral suppression after cessation of the therapy, we conducted a proof-of-concept study with a DNA vaccine comprising of most HBV genes plus genetically engineered interleukin-12 DNA (IL-12N222L) in 12 CHB carriers being treated with lamivudine (LAM). When the ex vivo and/or cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay was performed, the detectable HBV-specific IFN-gamma secreting T-cell responses were observed at the end of treatment and during a follow-up. These type 1T-cell responses, particularly CD4(+) memory T-cell responses could be maintained for at least 40 weeks after the therapy and correlated with virological responses, but not with alanine aminotransferase elevation. Moreover, DNA vaccination under LAM treatment appeared to be well-tolerated and showed 50% of virological response rate in CHB carriers. Thus, a combination therapy of the DNA vaccine with chemotherapy may be one of new immunotherapeutic methods for the cure of CHB.


Subject(s)
Genetic Therapy/methods , Hepatitis B Vaccines/administration & dosage , Hepatitis B virus/genetics , Hepatitis B, Chronic/immunology , T-Lymphocytes/immunology , Vaccines, DNA/administration & dosage , Adult , Antiviral Agents/therapeutic use , Combined Modality Therapy , Female , Genetic Engineering , Hepatitis B virus/immunology , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/therapy , Heterozygote , Humans , Immunologic Memory , Interferon-gamma/immunology , Interleukin-12/genetics , Lamivudine/therapeutic use , Male , Middle Aged , Recurrence , Virus Replication
16.
Gene Ther ; 13(4): 330-8, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16195699

ABSTRACT

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF family, is a type II transmembrane cytokine molecule. Soluble TRAIL has been shown to induce apoptosis in a wide variety of cancer cells in vitro and to suppress tumor growth specifically without damaging normal cells and tissues in vivo. In our previous report, we have demonstrated that an artificial gene encoding the polypeptide composed of the three functional elements (a secretion signal, a trimerization domain and an apoptosis-inducing moiety of TRAIL gene sequence) expresses and secretes highly apoptotic trimeric TRAIL into the culture supernatant. Here, as an approach to TRAIL-based cancer gene therapy, we developed an adenoviral vector delivering the gene that encodes our secretable trimeric TRAIL (stTRAIL). This adenovirus (Ad-stTRAIL) potently induced apoptosis in vitro in cancer cell lines such as HeLa, MDA-MB-231, A549, HCT116 and U-87MG. In an animal xenograft tumor model bearing a human glioma cell line U-87MG, intratumoral delivery of Ad-stTRAIL dramatically suppressed tumor growth without showing detectable adverse side effects. Histological analysis revealed that Ad-stTRAIL suppresses tumor growth by inducing apoptotic cell death. Contrary to the known rapid clearance of systemically delivered TRAIL protein from the blood circulation, stTRAIL expressed by Ad-stTRAIL in tumor tissues persisted for more than 4 days. In a comparison of tumor suppressor activity between Ad-stTRAIL and Ad-flTRAIL (delivering the full-length TRAIL gene) after mixing infected cells with uninfected cells and implanting these mixed cells in nude mice, Ad-stTRAIL showed higher tumor suppressor activity than that of Ad-flTRAIL. Our data reveal that a gene therapy using Ad-stTRAIL has a promising potential to treat human cancers including gliomas.


Subject(s)
Adenoviridae/genetics , Apoptosis Regulatory Proteins/metabolism , Genetic Therapy/methods , Genetic Vectors/administration & dosage , Glioma/therapy , Membrane Glycoproteins/metabolism , Neoplasms, Nerve Tissue/therapy , Tumor Necrosis Factor-alpha/metabolism , Animals , Apoptosis/genetics , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/therapeutic use , Cell Line, Tumor , Cells, Cultured , Gene Expression , Genetic Vectors/genetics , Glioma/pathology , Histocytochemistry , Humans , Male , Membrane Glycoproteins/genetics , Membrane Glycoproteins/therapeutic use , Mice , Mice, SCID , Neoplasm Transplantation , Neoplasms, Nerve Tissue/pathology , TNF-Related Apoptosis-Inducing Ligand , Transplantation, Heterologous , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/therapeutic use
17.
Dig Liver Dis ; 37(10): 799-802, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16023901

ABSTRACT

A rare case of double cancer with situs ambiguus with polysplenia is presented. A 58-year-old patient was initially diagnosed with an early gastric cancer. On evaluation, the computed tomography of the abdomen demonstrated situs ambiguus with polysplenia. We performed a subtotal gastrectomy with the stomach being reconstructed in a Billroth-II fashion. Three months after the operation, he again visited our department complaining nausea and dysphagia. Examinations confirmed the other oesophageal malignancy with advanced stage. Because of unfamiliarity to situs anomaly and rarity of double cancer, we missed the other coexistent cancer. This is the first case presentation of a double carcinoma occurring in a patient with situs ambiguus with polysplenia. The literature is reviewed and the importance of preoperative evaluation is discussed.


Subject(s)
Adenocarcinoma/diagnosis , Esophageal Neoplasms/diagnosis , Neoplasms, Multiple Primary/diagnosis , Preoperative Care , Situs Inversus/diagnosis , Spleen/abnormalities , Stomach Neoplasms/diagnosis , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Biomarkers, Tumor/blood , CA-19-9 Antigen/blood , Carcinoembryonic Antigen/blood , Endoscopy, Gastrointestinal , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/surgery , Gastrectomy , Gastroenterostomy , Humans , Male , Middle Aged , Neoplasm Staging , Neoplasms, Multiple Primary/diagnostic imaging , Neoplasms, Multiple Primary/surgery , Situs Inversus/diagnostic imaging , Situs Inversus/surgery , Splenic Diseases/complications , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery , Tomography, X-Ray Computed
18.
Diabet Med ; 21(10): 1141-3, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15384963

ABSTRACT

AIMS: To determine the prevalence of metabolic syndrome according to the criteria of the Adult Treatment Panel III (ATP III) and the World Health Organization (WHO). METHODS: Data were collected from 1108 subjects over 40 years of age in the Chongup district, a rural area of South Korea. We evaluated the prevalence and clinical characteristics of metabolic syndrome according to the two criteria. RESULTS: According to the ATP III criteria, the prevalence of central obesity was 0.2% in men and 27.3% in women, which is much lower than the prevalence of central obesity in Americans. However, the prevalence of metabolic syndrome was similar to the prevalence in Americans. Of the Korean subjects over 40 years of age, 29.4% and 39.2% had metabolic syndrome according to the ATP III and WHO criteria, respectively. Metabolic syndrome according to the ATP III criteria was associated with insulin resistance, but not with microalbuminuria. CONCLUSIONS: Metabolic syndrome has a high prevalence in South Koreans despite the low prevalence of obesity and/or central obesity.


Subject(s)
Metabolic Syndrome/epidemiology , Adult , Age Distribution , Aged , Female , Humans , Korea/epidemiology , Male , Middle Aged , Prevalence , Rural Health , Sex Distribution
19.
Xenobiotica ; 34(11-12): 973-82, 2004.
Article in English | MEDLINE | ID: mdl-15801542

ABSTRACT

The purpose of this paper was to characterize cytochrome P450 (CYP) enzymes involved in N-dealkylation of a new oral erectogenic, DA-8159 to DA-8164, a major circulating active metabolite, in human liver microsomes and to investigate the inhibitory potential of DA-8159 on CYP enzymes. CYP3A4 was identified as the major enzyme responsible for DA-8159 N-dealkylation to DA-8164 based on correlation analysis and specific CYP inhibitor and antibody-mediated inhibition study in human liver microsomes, and DA-8159 metabolism in cDNA expressed CYP enzymes. There is the possibility of drug-drug interactions when prescribing DA-8159 concomitantly with known inhibitors or inducers of CYP3A4. DA-8159 was found to be only a very weak inhibitor of eight major CYPs (1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4), the largest inhibition occurring against CYP2D6 (IC5o 67.7 microM) in human liver microsomes. Drug-drug interactions would not be predicted on the basis of DA-8159 inhibiting the metabolism of coadministered drugs.


Subject(s)
Cytochrome P-450 Enzyme Inhibitors , Cytochrome P-450 Enzyme System/metabolism , Microsomes, Liver/metabolism , Protein Interaction Mapping/methods , Pyrimidines/chemistry , Pyrimidines/metabolism , Cells, Cultured , Cytochrome P-450 CYP3A , Enzyme Activation , Enzyme Inhibitors/metabolism , Erectile Dysfunction/drug therapy , Humans , Kinetics , Male , Pyrimidines/therapeutic use , Sulfonamides
20.
Int J Clin Pharmacol Ther ; 41(12): 593-6, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14692709

ABSTRACT

AIM: To study a comparative bioavailability of Liverman capsule to Legaion capsule and Silymarin tablet (which contain silibinin) in 24 healthy volunteers. VOLUNTEERS AND METHODS: Twenty-four healthy male Korean volunteers received each medicine at the silibinin dose of 120 mg in a 3 x 3 crossover study. There was a 1-week washout period among the doses. Plasma concentrations of silibinin were monitored by a high-performance liquid chromatography for over a period of 12 hours after the administration. AUCinf (the area under the plasma concentration-time curve from time zero to time infinity) was calculated by the trapezoidal rule extrapolation method. Cmax (maximum plasma drug concentration) and tmax (time to reach a Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUCinf, AUC(0-12h), and Cmax and untransformed tmax. RESULTS: After an oral administration of Liverman capsule, the pharmacokinetic parameters of silibinin, such as AUC(0-12h) (5.59, 4.24 and 13.9 microg/ml x h for Legalon capsule, Silymarin tablet and Liverman capsule, respectively) and AUCinf (6.00, 4.63 and 15.1 microg/ml x h) were significantly greater, Cmax (1.33, 1.13 and 6.04 microg/ml) was significantly higher and tmax (1.83, 2.10 and 0.875 h) was significantly faster than those after Legalon capsule and Silymarin tablet. CONCLUSION: These results indicate that the absorption and the extent of relative oral bioavailability of silibinin after Liverman capsule were significantly faster and greater, respectively, than those after Legalon capsule and Silymarin tablet.


Subject(s)
Silymarin/pharmacokinetics , Absorption , Administration, Oral , Adult , Area Under Curve , Biological Availability , Capsules , Humans , Male , Silybin , Silymarin/administration & dosage , Tablets
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