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1.
Clin Transl Oncol ; 18(6): 625-31, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26459257

ABSTRACT

PURPOSE: To analyze the expression of c-Met, and to investigate correlations between the expression of c-Met, clinicopathologic variables, and survival in patients undergoing curative surgery followed by adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer. METHODS: Ninety EHBD cancer patients who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled. Expression of c-Met was assessed with immunohistochemical staining on tissue microarray. The correlation between clinicopathologic variables and survival outcomes was evaluated using Kaplan-Meier method and Cox proportional hazard model. RESULTS: On univariate analysis, 66 patients (76.7 %) showed c-Met expression. c-Met expression had a significant impact on 5-year overall survival (OS) (43.0 % in c-Met(+) vs. 25.0 % in c-Met(-), p = 0.0324), but not on loco-regional relapse-free survival or distant metastasis-free survival (DMFS). However, on multivariate analysis incorporating tumor location and nodal involvement, survival difference was not maintained (p = 0.2940). Tumor location was the only independent prognostic factor predicting OS (p = 0.0089). Hilar location tumors, nodal involvement, and poorly differentiated tumors were all identified as independent prognostic factors predicting inferior DMFS (p = 0.0030, 0.0013, and 0.0037, respectively). CONCLUSIONS: This study showed that c-Met expression was not associated with survival outcomes in EHBD cancer patients undergoing curative resection followed by adjuvant chemoradiotherapy. Further studies are needed to fully elucidate the prognostic value of c-Met expression in these patients.


Subject(s)
Bile Duct Neoplasms/pathology , Biomarkers, Tumor/analysis , Proto-Oncogene Proteins c-met/biosynthesis , Adult , Aged , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/therapy , Bile Ducts, Extrahepatic/pathology , Chemoradiotherapy, Adjuvant , Digestive System Surgical Procedures , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Proto-Oncogene Proteins c-met/analysis , Tissue Array Analysis , Young Adult
2.
Clin Transl Oncol ; 17(10): 825-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26041722

ABSTRACT

BACKGROUNDS: As for intrahepatic cholangiocarcinoma, the most frequent site of failure after curative intent resection is the liver. We identified the risk factors for locoregional recurrence after curative intent resection for intrahepatic cholangiocarcinoma. METHODS: Medical records of 115 patients treated with surgical resection alone for intrahepatic cholangiocarcinoma from November 2000 to December 2010 were retrospectively reviewed. Locoregional failure was defined as recurrence within 20 mm from resection margin or regional lymph node. Overall survival and locoregional recurrence rates were analyzed using Kaplan-Meier methods, and the prognostic factors were analyzed using Cox proportional hazards model. RESULTS: Median follow-up duration of surviving patients was 61 months (range 8-139). Sixty-six patients had recurrence, and 45 of 66 patients (68 %) had locoregional recurrence. The 5-year overall survival and locoregional control rates were 49.1 and 51.6 %, respectively. ≥ T2b disease and R1 resection were associated with locoregional recurrence in multivariate analysis. Patients were divided into two groups whether these risk factors exist or not. The 5-year locoregional control rates of low (no risk factor n = 64) and high (1 or 2 risk factors n = 51) risk groups were 62.5 and 34.7 %, respectively (P = 0.001). CONCLUSIONS: After curative intent resection, locoregional control and survival of patients with intrahepatic cholangiocarcinoma were far from satisfactory. Further studies are needed to evaluate the potential benefit of adjuvant locoregional treatment such as radiotherapy for patients with high-risk factors (≥ T2b disease or R1 resection).


Subject(s)
Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/surgery , Cholangiocarcinoma/surgery , Hepatectomy , Neoplasm Recurrence, Local/epidemiology , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/pathology , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Proportional Hazards Models , Radiotherapy, Adjuvant , Retrospective Studies , Risk Factors , Survival Rate , Treatment Outcome
3.
Br J Radiol ; 88(1052): 20150144, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25996578

ABSTRACT

OBJECTIVE: To evaluate interfractional and intrafractional movement of patients with rectal cancer during radiotherapy with electronic portal imaging device (EPID) and surface infrared (IR) markers. METHODS: 20 patients undergoing radiotherapy for rectal cancer with body mass index ranging from 18.5 to 30 were enrolled. Patients were placed in the prone position on a couch with a leg pillow. Three IR markers were put on the surface of each patient and traced by two stereo cameras during radiotherapy on a twice-weekly basis. Interfractional isocentre movement was obtained with EPID images on a weekly basis. Movement of the IR markers was analysed in correlation with the isocentre movement obtained from the EPID images. RESULTS: The maximum right-to-left (R-L) movement of the laterally located markers in the horizontal isocentre plane was correlated with isocentre translocation with statistical significance (p = 0.018 and 0.015, respectively). Movement of the surface markers was cyclical. For centrally located markers, the 95% confidence intervals for the average amplitude in the R-L, cranial-to-caudal (C-C) and anterior-to-posterior (A-P) directions were 0.86, 2.25 and 3.48 mm, respectively. In 10 patients, intrafractional movement exceeding 5 mm in at least one direction was observed. Time-dependent systematic movement of surface markers during treatment, which consisted of continuous movement towards the cranial direction and a sail back motion in the A-P direction, was also observed. CONCLUSION: Intrafractional movement of surface markers has both cyclic components and time-dependent systematic components. Marker deviations exceeding 5 mm were mainly seen in the A-P direction. Pre- or post-treatment EPID images may not provide adequate information regarding intrafractional movement because of systematic movement in the A-P direction during radiotherapy. ADVANCES IN KNOWLEDGE: This work uncovered a sail back motion of patients in the A-P direction during radiotherapy. Pre- or post-treatment EPID images may not provide accurate positioning of patients in the A-P direction because of this time-dependent intrafractional motion.


Subject(s)
Rectal Neoplasms/radiotherapy , Adult , Aged , Female , Humans , Infrared Rays , Male , Middle Aged , Movement , Pilot Projects , Prone Position , Time Factors
4.
Br J Cancer ; 110(6): 1420-6, 2014 Mar 18.
Article in English | MEDLINE | ID: mdl-24481403

ABSTRACT

BACKGROUND: To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). METHODS: We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. RESULTS: After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (<13 vs ≥13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. CONCLUSIONS: ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.


Subject(s)
Breast Neoplasms/therapy , Lymph Nodes/pathology , Lymphatic Irradiation/methods , Adult , Aged , Breast Neoplasms/pathology , Disease-Free Survival , Female , Humans , Lymph Nodes/surgery , Lymphatic Metastasis , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Retrospective Studies , Young Adult
5.
Strahlenther Onkol ; 189(9): 753-8, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23907137

ABSTRACT

PURPOSE: The purpose of this research was to analyze the relationship between dose-volumetric parameters and the development of diabetes mellitus (DM) in patients treated with chemoradiotherapy (CRT) following curative resection for upper gastrointestinal (GI) cancers. PATIENTS AND METHODS: Medical records of patients who underwent postoperative CRT following curative resection, either pancreaticoduodenectomy (PD) or pylorus preserving pancreaticoduodenectomy (PPPD) for upper GI cancers including pancreas, biliary, ampullary, and duodenal cancers, between January 2006 and December 2008 were retrospectively reviewed. A total of 42 patients who were regularly followed for at least 2 years were included for analysis. Dose-volumetric parameters such as remnant pancreatic volume, mean dose, maximum dose (Dmax), and percentage of volume receiving specific dose or more were obtained from pre- and postoperative CT scan images and treatment plan. RESULTS: Dmax and V50 (percentage of volume receiving at least 50 Gy) were statistically significant factors for the development of DM (p = 0.013, p = 0.031, respectively). The sensitivity and specificity of Dmax was 0.875 and 0.559, with cut-off value of 51.1 Gy, respectively. V50 had sensitivity of 0.875 and specificity of 0.618 for cut-off value of 16 %. No patient-related factor other than pretreatment cerebrovascular events was associated with the development of DM. On multivariate analysis, V50 was the only factor with statistical significance (p = 0.028), whereas Dmax showed borderline significance (p = 0.079). CONCLUSION: V50 was the only independent factor associated with the development of diabetes and may function as guideline to predict the development of DM in patients receiving CRT following curative resection.


Subject(s)
Chemoradiotherapy, Adjuvant/mortality , Diabetes Mellitus/mortality , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/therapy , Pancreaticoduodenectomy/mortality , Postoperative Care/mortality , Radiotherapy Dosage , Adult , Causality , Comorbidity , Female , Humans , Incidence , Male , Middle Aged , Prognosis , Republic of Korea/epidemiology , Retrospective Studies , Risk Assessment , Survival Analysis , Survival Rate , Treatment Outcome , Tumor Burden
6.
Br J Cancer ; 108(7): 1425-31, 2013 Apr 16.
Article in English | MEDLINE | ID: mdl-23481187

ABSTRACT

BACKGROUND: We aimed to determine the role of palliative resection in metastatic colorectal cancer (mCRC) and ascertain which patient populations would benefit most from this treatment. METHODS: A total of 1015 patients diagnosed with mCRC at Seoul National University Hospital between 2000 and 2009 were retrospectively studied. RESULTS: Of the 1015 patients, 168 patients with only liver and/or lung metastasis received curative resection. The remaining 847 patients were treated with palliative chemotherapy and/or palliative resection combined with best supportive care. Palliative resection was performed in 527 (62.2%) cases (complete resection with negative margin (R0) in 93, R1/2 in 434). Resected patients had a more prolonged median overall survival (OS) than unresected patients (21.3 vs 14.1 months; P<0.001). In multivariate analysis, R0 resection was found to be associated with a superior OS compared with R1/2 resection (51.3 vs 19.1 months; P<0.001) and no resection (51.3 vs 14.1 months; P<0.001). When we performed propensity score matching, palliative resection was found to be related to prolonged OS (hazard ratio=0.72, 95% confidence interval=0.59-0.89; P=0.003). CONCLUSION: Palliative resection without residual disease and chemotherapy confers a longer-term survival outcome than palliative chemotherapy alone in mCRC patient subset.


Subject(s)
Colorectal Neoplasms/surgery , Palliative Care/methods , Adolescent , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Prognosis , Retrospective Studies , Treatment Outcome , Young Adult
7.
Br J Radiol ; 85(1015): e323-9, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22745211

ABSTRACT

OBJECTIVE: The purpose of this study is to compare the dose-volumetric results of RapidArc (RA Varian Medical Systems, Palo Alto, CA) with those of intensity-modulated radiation therapy (IMRT) for hepatocellular carcinoma. METHODS: 20 patients previously treated for hepatocellular carcinoma were the subjects of this planning study. 10 patients were treated for portal vein tumour thrombosis (Group A), and 10 patients for primary liver tumour (Group B). Prescription dose to the planning target volume was 54 Gy in 30 fractions, and the planning goal was to deliver more than 95% of prescribed dose to at least 95% of planning target volume. RESULTS: In Group A, mean doses to liver were increased with RA vs IMRT (22.9 Gy vs 22.2 Gy, p=0.0275). However, V(30 Gy) of liver was lower in RA vs IMRT (31.1% vs 32.1%, p=0.0283). In Group B, in contrast, neither mean doses nor V(30 Gy) of liver significantly differed between the two plans. V(35 Gy) of duodenum and V(20 Gy) of kidney were decreased with RA in Groups A and B, respectively (p=0.0058 and 0.0124, respectively). Both maximal doses to spinal cord and monitor unit were significantly lower in the RA plan, regardless of the group. CONCLUSION: The dose-volumetric results of RA vs IMRT were different according to the different target location within the liver. In general, RA tended to be more effective in the sparing of non-liver organs at risk such as duodenum, kidney, and/or spinal cord. Moreover, RA was more efficient in the treatment delivery than IMRT in terms of total monitor unit used.


Subject(s)
Carcinoma, Hepatocellular/radiotherapy , Liver Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Adult , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Cohort Studies , Female , Follow-Up Studies , Hepatectomy/methods , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Phantoms, Imaging , Prospective Studies , Radiation Injuries/prevention & control , Radiotherapy Dosage , Radiotherapy, Adjuvant , Radiotherapy, Conformal/methods , Risk Assessment , Survival Rate , Treatment Outcome
8.
Strahlenther Onkol ; 188(5): 388-92, 2012 May.
Article in English | MEDLINE | ID: mdl-22402869

ABSTRACT

PURPOSE: The goal of this work was to analyze the outcome of adjuvant chemoradiotherapy for patients with gallbladder cancer who underwent surgical resection and to identify the prognostic factors for these patients. PATIENTS AND METHODS: Between August 1989 and November 2006, 47 patients with gallbladder cancer underwent surgical resection followed by adjuvant radiotherapy. There were 21 males and 26 females, and median age was 60 years (range 44-75 years). Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes up to 40-50 Gy at 2 Gy/fraction; 41 patients also received intravenous 5-fluorouracil as a radiosensitizer. Median follow-up duration was 48 months for survivors. RESULTS: There were 2 isolated locoregional recurrences, 14 isolated distant metastases, and 7 combined locoregional and distant relapses. The 5-year overall survival rate was 43.7%. According to the extent of resection, the 5-year overall survival rates were 52.8%, 20.0%, and 0% in R0-, R1-, and R2-resected patients, respectively (p = 0.0038). On multivariate analysis incorporating extent of resection, T stage, N stage, performance of lymph node dissection, and histologic differentiation, extent of resection was the only prognostic factor associated with overall survival (p = 0.0075). Among the 37 patients with R0 resection, there was no difference of 5-year overall survival rates in patients with N0, N1, and Nx diseases (46.2%, 60.0%, and 44.4%, respectively, p = 0.6246). As for significant treatment-related morbidity, there was only 1 patient with grade 4 gastric ulcer. CONCLUSION: Adjuvant chemoradiotherapy after R0 resection can achieve a good long-term survival rate in gallbladder cancer patients, even in those with lymph node metastases, and may play a role for patients who underwent R0 resection of primary tumor without lymph node dissection.


Subject(s)
Adenocarcinoma/mortality , Adenocarcinoma/therapy , Chemoradiotherapy , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/therapy , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Female , Fluorouracil/therapeutic use , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/surgery , Humans , Male , Middle Aged , Radiation-Sensitizing Agents/therapeutic use , Radiotherapy, Adjuvant , Retrospective Studies , Survival Analysis
9.
Eur J Neurol ; 17(3): 434-42, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19922458

ABSTRACT

BACKGROUND AND PURPOSE: Biological aspirin resistance (AR) has been recognized as an important cause of clinical AR. Recent studies have reported the beneficial effects of cilostazol for the prevention of cardiovascular diseases. This study investigated whether addition of cilostazol to aspirin in ischaemic stroke patients can reduce AR. METHODS: In this double-blind multicenter trial, 244 aspirin users with ischaemic stroke were randomly assigned to receive cilostazol 100 mg twice daily or to placebo. Antiplatelet function was assessed using the VerifyNow Aspirin system. The primary end-point was the incidence of AR, which was measured as aspirin resistance unit (ARU) > or =550 after 4-week treatment. RESULTS: The incidence of AR after treatment in cilostazol group was not significantly different from that in placebo (8.8% vs. 10.9%, P = 0.578). However, AR decreased from 12.8% to 8.8% in cilostazol group, whereas it was not changed in the placebo group. The mean ARU after treatment were also lower in the cilostazol group (456.9 +/- 56.0 vs. 470.7 +/- 67.2, P = 0.081). Cilostazol addition did not prolong bleeding time. CONCLUSIONS: Although this was a negative study, our findings disclosed a trend toward enhanced antiplatelet effects when cilostazol was added to aspirin in ischaemic stroke patients. Combination of aspirin and cilostazol might be a treatment option in the ischaemic stroke patients with AR.


Subject(s)
Aspirin/therapeutic use , Brain Ischemia/drug therapy , Drug Resistance/drug effects , Platelet Aggregation Inhibitors/therapeutic use , Stroke/drug therapy , Tetrazoles/therapeutic use , Aspirin/administration & dosage , Bleeding Time , Brain Ischemia/diagnosis , Brain Ischemia/epidemiology , Cilostazol , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Incidence , Male , Middle Aged , Platelet Aggregation Inhibitors/administration & dosage , Prognosis , Stroke/diagnosis , Stroke/epidemiology , Tetrazoles/administration & dosage , Treatment Outcome
10.
Transplant Proc ; 38(5): 1314-9, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16797290

ABSTRACT

Transforming growth factor (TGF)-beta is involved in the pathogenesis of chronic cyclosporine nephrotoxicity (CyAN). Since the expression of TGF-beta induced gene h3 (betaig-h3) is up-regulated by TGF-beta, we evaluated the potential role of betaig-h3 as a sensitive urinary marker to monitor the progression/regression of chronic CyAN. Urinary betaig-h3 levels were determined using an enzyme-linked immunosorbent assay in nine patients with chronic CyAN and 13 patients with stable graft function. We scored the extent of tubulointerstitial fibrosis (TIF) and using immunoperoxidase labeling, determined betaig-h3 expression in renal tissues of patients with chronic CyAN. Urinary betaig-h3 excretion was higher in chronic CyAN compared to control subjects (173.4+/-26.0 vs 62.6+/-5.0 ng/mg creatinine, P<.01). In chronic CyAN, the degree of TIF correlated with increased urinary betaig-h3 levels (r=.785, P<.05). In kidneys with chronic CyAN, betaig-h3 labeling was more prominent at the basement membranes (BM) of the tubules where inflammatory cells had infiltrated the surrounding interstitium. Moreover, the BM of the atrophied tubules and their surrounding interstitium were strongly labeled. Urinary betaig-h3 levels decreased from 173.4+/-26.0 to 64.9+/-14.4 ng/mg creatinine at 1 month after discontinuation of CyA or reduction in CyA dosage (P<.01) despite unchanged serum creatinine levels. Urinary betaig-h3 levels increased in patients with chronic CyAN and decreased after discontinuation or reduction of CyA dosage. Our results suggested that urinary betaig-h3 levels could be used as a sensitive urinary marker to monitor the progression or regression of chronic CyAN.


Subject(s)
Cyclosporine/toxicity , Extracellular Matrix Proteins/genetics , Kidney Transplantation/pathology , Transforming Growth Factor beta/urine , Adult , Biomarkers/urine , Biopsy , Extracellular Matrix Proteins/urine , Female , Humans , Male , Middle Aged , Transforming Growth Factor beta/genetics
11.
Int J Radiat Biol ; 76(7): 923-7, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10923616

ABSTRACT

PURPOSE: To analyse chromosome aberrations in nuclear-power-plant workers taking account of the mean lifetime of lymphocytes (MLTL). MATERIALS AND METHODS: Analysis of chromosome aberrations was performed on peripheral lymphocytes from 395 nuclear-power-plant workers and 135 controls. An equivalent acute dose (EAD) was calculated utilizing MLTL values of either 4.3 or 10 years. RESULTS: Using an MLTL value of 10 years produced an EAD range of 0.O1 mSv -182mSv(mean 46.6mSv), while using an MLTL, of 4.3 years produced results ranging from 0.01 mSv to 86.2 mSv (mean 23.4 mSv). A significant increase of chromosome-type exchange by the equivalent acute dose was observed using an MLTL of either 10 or 4.3 years when including the control in the analysis, but a significant increase was not seen when only the exposed was considered. A significant increase of chromosome-type deletion by EAD was seen even when only the exposed group was considered. CONCLUSIONS: EAD values based on an MLTL of either 4.3 or 10 years, as well as cumulative dose, showed no significant association with chromosome aberrations, when radiation workers only were analysed. The narrow dose range examined in this study might have contributed to this finding.


Subject(s)
Chromosome Aberrations , Lymphocytes/radiation effects , Occupational Exposure , Power Plants , Dose-Response Relationship, Radiation , Humans
12.
Diabetes ; 49(7): 1239-48, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10909984

ABSTRACT

Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have been associated with decreased blood flow in the retina and peripheral nerves of diabetic animals and may be related to the development of pathologies in these tissues. Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells. We have characterized the mechanism by which elevation of glucose is increasing ET-1 mRNA expression in capillary bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5 mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. By immunoblot analysis, PKC-beta2 and -delta isoforms in BREC were significantly increased relative to other isoforms in the membranous fractions when glucose level was increased. Overexpression of PKC-beta1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy.


Subject(s)
Endothelin-1/genetics , Endothelium, Vascular/physiology , Glucose/pharmacology , Protein Kinase C/metabolism , Retinal Vessels , Transcription, Genetic/drug effects , Animals , Capillaries , Cattle , Cells, Cultured , Endothelium, Vascular/drug effects , Enzyme Activation , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , Indoles/pharmacology , Isoenzymes/metabolism , Maleimides/pharmacology , Pericytes/drug effects , Pericytes/physiology , Protein Kinase C beta , Protein Kinase C-alpha , Protein Kinase C-delta , RNA, Messenger/genetics
13.
Circulation ; 101(6): 676-81, 2000 Feb 15.
Article in English | MEDLINE | ID: mdl-10673261

ABSTRACT

BACKGROUND: The vasodilatory effect of insulin can be acute or increase with time from 1 to 7 hours, suggesting that insulin may enhance the expression of endothelial nitric oxide synthase (eNOS) in endothelial cells. The objective of the present study was to characterize the extent and signaling pathways by which insulin regulates the expression of eNOS in endothelial cells and vascular tissues. METHODS AND RESULTS: Physiological concentrations of insulin (10(-10) to 10(-7) mmol/L) increased the levels of eNOS mRNA, protein, and activity by 2-fold after 2 to 8 hours of incubation in cultured bovine aortic endothelial cells. Insulin enhanced eNOS gene expression in microvessels isolated from Zucker lean rats but not from insulin-resistant Zucker fatty rats. Inhibitors of phosphatidylinositol-3 kinase (PI-3 kinase) decreased the effect of insulin on eNOS gene expression, but a general protein kinase C (PKC) inhibitor, GF109203X or PKCbeta isoform inhibitor, LY333531 enhanced eNOS expression. In contrast, PKC activators inhibited both the activation by insulin of PI-3 kinase and eNOS mRNA levels. Overexpression of PKCbeta isoform in endothelial cells inhibited the stimulation by insulin of eNOS expression and PI-3 kinase activities in parallel. CONCLUSIONS: Insulin can regulate the expression of eNOS gene, mediated by the activation of PI-3 kinase, in endothelial cells and microvessels. Thus, insulin may chronically modulate vascular tone. The activation of PKC in the vascular tissues as in insulin resistance and diabetes may inhibit PI-3 kinase activity and eNOS expression and may lead to endothelial dysfunctions in these pathological states.


Subject(s)
Endothelium, Vascular/enzymology , Gene Expression Regulation, Enzymologic/drug effects , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Nitric Oxide Synthase/biosynthesis , Animals , Cattle , Cells, Cultured , Diabetes Mellitus/enzymology , Enzyme Inhibitors/pharmacology , Indoles/pharmacology , Maleimides/pharmacology , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type III , Phosphatidylinositol 3-Kinases/metabolism , Protein Kinase C/metabolism , Rats , Rats, Zucker , Signal Transduction/drug effects
14.
J Korean Med Sci ; 14(5): 565-70, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10576154

ABSTRACT

The benefits of radio-chemotherapy in HIV-negative primary central nervous system (CNS) lymphomas were analyzed in 40 patients, who received radiotherapy to the brain or craniospinal axis with the total dose of 4460-5940 cGy to the primary tumor. Radiotherapy was followed by systemic chemotherapy, mainly with the cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) regimen, in 16 of the patients. Follow-up ranged from four to 95 months with a median of 15 months. The relapse rate was 72.5%, and 83% of the relapses occurred within the radiation field. Median survival was 19 months and the two-year survival rate was 41%. Survival was significantly influenced by treatment method and radiation dose when measured by univariate analysis; median survival and the two-year survival rate was 29 months and 63% after radio-chemotherapy, while 13.5 month and 29% after radiotherapy alone (p= 0.027), and 22 months and 49% with doses of 50 Gy or more, but 12.5 months and 13% with doses less than 50 Gy (p=0.009). However, statistical significance was lost in multivariate analysis. These results might suggest the short-term efficacy of radio-chemotherapy, however, cautious observation is needed to confirm long-term effects.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/therapy , Lymphoma/therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/administration & dosage , Central Nervous System Neoplasms/mortality , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Epirubicin/administration & dosage , Female , Humans , Lymphoma/mortality , Male , Mechlorethamine/administration & dosage , Methotrexate/administration & dosage , Middle Aged , Neoplasm Recurrence, Local , Prednisolone/administration & dosage , Procarbazine/administration & dosage , Radiotherapy Dosage , Radiotherapy, Adjuvant/adverse effects , Survival Rate , Treatment Failure , Vincristine/administration & dosage
15.
Perit Dial Int ; 19 Suppl 2: S222-7, 1999.
Article in English | MEDLINE | ID: mdl-10406523

ABSTRACT

Many vascular diseases in diabetes are known to be associated with the activation of the diacylglycerol (DAG)-protein kinase C (PKC) pathway. The major source of DAG that is elevated in diabetes is de novo synthesis from glycolytic intermediates. Among the various PKC isoforms, the beta-isoform has been shown to be persistently activated in diabetic animals. Multiple lines of evidence have shown that many vascular alterations in diabetes--such as a decrease in the activity of Na+-K+-adenosine triphosphatase (Na+-K+-ATPase), and increases in extracellular matrix, cytokines, permeability, contractility, and cell proliferation--are caused by activation of PKC. Inhibition of PKC by two different kinds of PKC inhibitors, LY333531, a selective PKC-beta-isoform inhibitor, and d-alpha-tocopherol, were able to prevent or reverse the various vascular dysfunctions in diabetic rats. These results have also provided in vivo evidence that DAG-PKC activation could be responsible for the hyperglycemia-induced vascular dysfunctions in diabetes. Clinical studies are now being performed to clarify the pathogenic roles of the DAG-PKC pathway in developing vascular complications in diabetic patients.


Subject(s)
Diabetic Angiopathies/physiopathology , Protein Kinase C/physiology , Animals , Blood Glucose/analysis , Diabetic Angiopathies/metabolism , Diacylglycerol Kinase/metabolism , Enzyme Activation , Hemodynamics , Humans , Isoenzymes/metabolism , Protein Kinase C/metabolism
16.
J Korean Med Sci ; 14(2): 217-9, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10331572

ABSTRACT

Endometriosis of a surgical scar is rare and occurs mainly when a hysterectomy or Cesarean section was performed. We describe a 54-year-old woman with a large suprapubic mass as a definite case of a endomerioid carcinoma developing within the scar endometriosis following Cesarean section. Scar endometriosis, as well as endometriosis at other sites, can turn malignant. Endometrioid carcinoma is the most common histological pattern of malignant tumor arising in endometriosis. But clear cell carcinoma is very unusual. A case of primary clear cell carcinoma in endometriosis of a Cesarean section scar is described. To the best of our knowledge, this is the first documented case of endomerioid carcinoma developing within the scar endometriosis in Korea.


Subject(s)
Adenocarcinoma, Clear Cell/etiology , Carcinoma, Endometrioid/etiology , Cesarean Section/adverse effects , Cicatrix , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Clear Cell/surgery , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/surgery , Endometriosis/physiopathology , Female , Humans , Middle Aged , Tomography, X-Ray Computed/methods
17.
J Magn Reson Imaging ; 9(3): 428-34, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10194713

ABSTRACT

An intravascular magnetic resonance (MR) imaging catheter for high-resolution imaging of vessel walls was developed. The catheter design is based on an autoperfusion balloon catheter that allows passive perfusion of blood during balloon inflation. The blood enters a central lumen through multiple sideholes of the catheter shaft proximal to the balloon. A remotely tuned, matched, and actively decoupled, expandable single-loop radiofrequency coil was mounted onto the balloon to receive intravascular MR signals. The autoperfusion rate through the catheter was determined experimentally relative to perfusion pressure. The catheter concept was evaluated in vitro on human femoral artery specimens and in vivo in the internal carotid artery of two pigs. The proposed catheter design allowed for maintained blood perfusion during the acquisition of high-resolution intravascular images. During perfusion, image quality remained unaffected by flow, motion, and pulsatility artifacts. The availability of an autoperfused intravascular catheter design can be considered an important step toward high-resolution atherosclerotic plaque imaging in critical vessels such as the carotid and coronary arteries.


Subject(s)
Arteries/anatomy & histology , Arteries/physiology , Catheterization , Magnetic Resonance Angiography/instrumentation , Animals , Arteriosclerosis/diagnosis , Carotid Artery, Internal/anatomy & histology , Carotid Artery, Internal/physiology , Catheterization/instrumentation , Disease Models, Animal , Equipment Design , Equipment Safety , Female , Femoral Artery/anatomy & histology , Femoral Artery/physiology , Humans , In Vitro Techniques , Magnetic Resonance Angiography/methods , Models, Biological , Pulsatile Flow/physiology , Sensitivity and Specificity , Swine
18.
J Formos Med Assoc ; 96(5): 336-45, 1997 May.
Article in English | MEDLINE | ID: mdl-9170821

ABSTRACT

Sixty-one strains of Mycobacterium tuberculosis complex and 47 strains of nontuberculous mycobacteria were analyzed for fatty acids and enzyme profiles. Cellular fatty acids were extracted from bacteria, methylated and analyzed by gas liquid chromatography operated either manually (Perkin-Elmer) or by the automatic Microbial Identification System. The major cellular fatty acids in all mycobacterial species were C16:0 and C18:1. Tuberculostearic acid was found in all species with the exception of Mycobacterium gordonae. The fatty acids with a carbon-length longer than 20 could be detected only by conventional gas chromatography. Strains of M. tuberculosis had a high ratio of C26:0 to C24:0, and a relatively low ratio of C14:0 to C15:0. For determination of branched-chain fatty acids, the MIS provided more definitive results. The data indicated that the fatty acid profiles could provide rapid species identification. The results of the enzyme profile analysis using API-ZYM strips showed 39 different patterns from 59 strains of M. tuberculosis, and 41 different patterns from 46 nontuberculous mycobacteria strains, suggesting that enzyme profiles can also be used for strain characterization within the same species.


Subject(s)
Enzymes/analysis , Fatty Acids/analysis , Mycobacterium/chemistry , Chromatography, Gas , Mycobacterium/classification
19.
Health Care Women Int ; 18(3): 301-13, 1997.
Article in English | MEDLINE | ID: mdl-9256675

ABSTRACT

An ethnographic approach was used to explore the cultural practices of Hong Kong Chinese women during the postpartum period. Seven multiparous women were interviewed and asked to reflect on their self-care practices within the family home during the month after the birth of their first child. Content analysis was applied to the interviews and major categories identified: good food and bad blood, poisonous sex, dirt and prohibitions, rest and appeasing the placenta god, and competing loyalties. The indication is that these Chinese mothers had attempted to follow their personally constructed interpretations of traditional customary practices, being influenced by close family members, neighbors, and historical precedent. These women further outlined a number of personal variations to traditional practices in the face of increasingly Western influences. We provide insights into the complexity of issues modern Hong Kong Chinese women face in the first postpartum month and on a more global level highlight the importance of culturally sensitive and congruent nursing practice.


Subject(s)
Mothers/psychology , Postpartum Period/ethnology , Self Care/psychology , Adult , China/ethnology , Cultural Characteristics , Female , Hong Kong , Humans , Medicine, East Asian Traditional , Pregnancy , Surveys and Questionnaires , Transcultural Nursing
20.
J Mater Sci Mater Med ; 8(12): 881-6, 1997 Dec.
Article in English | MEDLINE | ID: mdl-15348809

ABSTRACT

Carbon fibre-reinforced polyetheretherketone (CF-PEEK) substrates were coated with titanium by vacuum-plasma-spraying and chemically treated in 10 M sodium hydroxide (NaOH) solution. After NaOH treatment, the specimens were immersed in simulated body fluid (SBF) containing ions in concentrations similar to those of human blood plasma. Scanning electron microscopy, energy-dispersive X-ray analysis and diffuse reflectance Fourier transformed-infrared spectroscopy were used to analyse the NaOH-treated VPS-Ti surface and the calcium phosphate layer formed during immersion in SBF. It was observed that a carbonate-containing calcium phosphate layer was formed on the NaOH-treated VPS-Ti surface during immersion in SBF, whereas no calcium phosphate precipitation occurred on the untreated surfaces. It is therefore concluded that vacuum-plasma-spraying with titanium and subsequent chemical modification in 10 M NaOH solution at 60 degrees C for 2 h is a suitable method for the preparation of bioactive coatings for bone ongrowth on CF-PEEK.

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