Inhibitory Effect on Angiogenesis of a Selective Cyclooxygenase-2 Inhibitor with using Mouse Mammary Tumor cells / 한국유방암학회지

PURPOSE: Angiogenesis plays a key role in the growth and metastasis of malignant tumor. Angiogenesis is reportedly enhanced by prostaglandins (PGs). Cyclooxygenase (COX)-2 is an inducible enzyme that catalyzes the formation of PGs from arachidonic acid. The COX enzyme system is composed of two isoenzymes, COX-1 and COX-2. Recent sources of experimental and epidemiological evidence suggest a significant role for the COX enzymes, particularly COX-2, in the pathogenesis of breast cancer. COX-2 overexpression in a murine mammary gland is sufficient to cause tumor formation. We performed our study to determine the effect of COX-2 inhibitor in a in vivo mouse mammary tumor (MMT) cell line. METHODS: In order to test our study, 24 C57BL/6 type mice (Jackson Laboratory, Bar Harbor, USA) were randomized to receive 35 days of either placebo supplemented diet (n=11) or a 1,500ppm celecoxib (CELEBREX, Pfizer Inc. St. Louis, USA) supplemented diet (n=13) beginning at day 0. At 14 days after the beginning day, 30 microliter of a 1% India ink solution that contained 500,000 of MMT cells or dye alone (control) was intradermally inoculated at each flank (day 14). The animals were sacrificed 21 days later (day 35) and skin specimens were harvested/processed for quantification of the microvessel density (MVD) that was associated with each inoculated site. The aortas that were isolated according to each treatment group at the time of animal sacrifice were used to create identical aortic ring angiogenesis assays (media 199 supplemented with 20% FBS). Explants were evaluated for 14 days in culture to determine both the rate of angiogenesis initiation (% of explants exhibiting the angiogenic phenotype) and the neovessel growth rate (using a subjective angiogenic index score for the wells exhibiting initiation). Analysis of variance (ANOVA) was used to evaluate the differences between groups for each assay. RESULTS: According to the immunohistochemical staining, celecoxib administration resulted in a parallel decrease in the MVD at both the control and MMT inoculated sites (22% and 21%, p = 0.025 and p = 0.010 respectively). On the aortic ring assay, the dietary treatment group was not significantly inhibited compared with the placebo group (75% and 63.3%, respectively, p = NS). However, dietary celecoxib administration significantly inhibited the angiogenic index of the neovessel growth rate (5.0 +/- 2.38 and 8.9 +/- 3.44, respectively, p < 0.001). CONCLUSION: These results suggest that a selective COX-2 inhibitor had an antiangiogenic effect on the in vivo tumor cells. We will perform more investigations of a selective COX-2 inhibitors, and these may will be crucial drugs to use as new chemotherapy agents for treating in cancer.

Inhibition Effect of Angiostatin and Endostatin on Human Angiogenesis

PURPOSE: Angiogenesis is a critical determinant of tumor growth and the development of metastasis. Angiostatin and endostatin have been used in a variety of in vitro and in vivo animal models as effective inhibitors of angiogenesis. However, human angiostatin and endostatin have not been tested against an intact human tissue target in vitro to determine its ability to achieve an antiangiogenic response. We performed our study to determine if human angiostatin and endostatin would inhibit the development of an angiogenic response (initiation) and to determine the subsequent growth (angiogenic index) of human vessels in a dose-dependent manner with a human placental vein angiogenesis model (HPVAM). METHODS: We used full thickness human placental vein discs cultured in three-dimensional fibrin-thrombin clots with an overlay of liquid media. Human angiostatin and endostatin were evaluated in concentrations ranging from 10-9 M to 10-4 M. A positive control containing 20% fetal bovine serum and a negative control using heparin and hydrocortisone 21-phosphate were also tested. RESULTS: Human angiostatin did not inhibit the initiation of an angiogenic response and the subsequent development of the angiogenic response (angiogenic index) at any concentration. Human endostatin significantly inhibited the initiation rate of an angiogenic response at a concentration of 10-4 M (p<0.001) and the subsequent development of an angiogenic response (angiogenic index) from a concentrations of 10-5 M to 10-4 M (p<0.001, p<0.001, respectively). CONCLUSION: We conclude that a very high concentration of human endostatin can inhibit the angiogenic response in human vascular tissue and that human angiostatin will not inhibit angiogenesis of normal human blood vessels in vitroThese results suggest that human endostatin has a more powerful antiangiogenic effect than human angiostatin, but we need further investigations of human angiostatin against an intact human tissue target.

Results of Surgical Treatment for Intrahepatic Duct Stones

BACKGROUND: The treatment of intrahepatic stones is difficult because of frequent recurrence and residual stones. There are several suggested methods of treatment which include surgical bile-uct exploration with or without biliary drainage, an endoscopic procedure, transhepatic cholangiolithotomy, and hepatic resection. METHODS: We reviewed the therapeutic results in 96 patients who had hepatolithiasis and received surgery at Soon Chun Hyang University Chunan Hospital during the 10 years from June 1987 to June 1997. We divided them into 2 groups: one was the group of patients receiving a hepatic resection with or without a drainage procedure (resection group), and the other was the group of patients receiving only a T-ube choledochostomy or drainage procedure (nonresection group). RESULTS: The male-to-female ratio was 1:1.74, and the most prevalent age group was the 5th decade (31.3%). The most common symptoms were epigastric pain (61%) and RUQ pain (60%), and the locations of stones were the right intrahepatic duct in 10 cases (10.4%), the left intrahepatic duct in 47 cases (49%), and both intrahepatic duct in 39 cases (40.6%). Operative methods were a resection in 29 cases and a nonresection in 67 cases. The incidence of residual stones were 31.0% in the hepatic resection group and 68.6% in the nonresection group. The postoperative complication rate was 20.6% in hepatic resection group and 38.8% in the nonresection group, and the follow-p study showed the good results (Good & Fair) for 92.5% of the hepatic resection group and 66.7% of the nonresection group. CONCLUSION: The hepatic resection with or without drainage is an adequate treatment for hepatolithiasis. It can eradicate localized intrahepatic calculi, irreversible biliary stricture, an atrophied segment, and, possibly, an associated cholangiocarcinoma, with good results in clinical evaluation.

The Correlation of Cardiovascular Risk Factors and Hearing Loss / 대한산업의학회지

To investigate the effects of cardiovascular risk factors on hearing loss, hearing threshold and cardiovascular risk factors such as blood pressure, hematologic values, and serum lipid levels of 3,827 persons who visited the Health Center of a University Hospital in Kumi for health examination from January 1, 1995 to July 31, 1997 were analysed. The results were summarized as follows ; 1. Hearing threshold was shifted highly in both sex groups with age increased. Smoking did not influence increase of hearing loss, but drinking alcohol amount increased hearing threshold when sex was adjusted. The most highly increased hearing threshold showed among farmers group, but next was blue collars group. Hearing threshold increasing basis with BMI increased. 2. Systolic and diastolic blood pressure and hematocrit value increased the hearing threshold in both sex groups, but hemoglobin value did not related to the hearing threshold. 3. Total cholesterol, LDL-cholesterol, triglyceride, and atherosclerosis index were significantly increased with the grade of hearing lose increased, when age was adjusted. 4. In the logistic regression analysis, the atherosclerosis index, age, and hematocrit value revealed risk factors which contributed in that orders, though the values were small they showed statistical significances, but the risks were lowered when hemoglobin values increased, in both sex groups. Consequently, hyperlipidemia was significantly related to the hearing loss when age was adjusted.

Ultrasonography and Plain Film Versus Intravenous Urography in Urinary calculi

BACKGROUND: Urography(IVU) is considered the best first investigation in patient with suspected urinary calculi, but recently ultrasonography(USG), combined with a plain film of the abdomen, has been suggested as an alternative. METHODS: We undertaken study to see if this approch can be used in emergency patients and outpatients by radiologists with different amounts of ultrasound experence. Some 192 patients with suspected urinary colic presenting to Koo Hospital Emergency Department and Youngnam Universith Hospital outward Department(IM, URO, FM) over 12-month period were studied. They had a plain abdominal film(KUB) and USG examination of the kidney, ureter, bladder following hydration and subsequently underwent IVU. Of these, 22 patients passed a stone before their IVU. The data analysis was performed on the remaining 170 patients. Urography was used as the gold standard. RESULTS: Some 170 patients subsequently underwent IVU at a mean interval of 1.8 days after the ultrasound examination. In 91 of 170 patients the IVU was positive. In 97 of 170 patients the combination of JUB plus USG was positive, leaving three false negative KUB plus USG. Thus the sensitivity of KUB plus USG was 97%, specificity was 89%, positive predictive value was 91%, and negative predictive value was 96%. CONCLUSIONS: Our findings in this study suggest that in the hydrated patient the combination of KUB plus US is a very sensitive and relative specific screening test. Because of the high negative predictive value of KUB plus US, urography is not likely to be helpful when KUB plus US are negative. Urography is indicated only if KUB plus US findings are equivocal or if intervention is necessa.ry.

Using the Color Doppler Signal for Diagnosis of Breast Cancer

Breast ultrasound and mammography are established procedures for the diagnosis of breast masses while new technology is opening the door for early cancer diagnosis. The limitation of ultrasound and mammography is that they are only based on physical properties. Recently, using a color doppler system, detection of color flow signal and a resistance index that depend on the blood flow and the blood velocity was applied for diagnosis of breast malignancy. Sixty-five patients admitted for breast surgery were studied. The final diagnosis was made by pathology for thirty malignancies and thirty-five benign lesions. The color doppler measurements on the breast lesions were made preoperatively. The following parameter were assessed :flow velocity, color signal grade and resistance index. The results are as follows: 1) Color signals were detected in twenty-four of the thirty malignancies and in seven of thirty-five benign lesions. 2) Malignant lesions showed a significantly higher maximum velocity (mean=12.52 cm/sec vs 6.34 cm/sec). 3) The resistance index values in the malignancies was higher compared to that in the benign lesions (P 0.05). Color doppler flow examination is a useful method for evaluation of benign and malignant breast lesions.