• Journal of Gastric Cancer
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• v.21 no.2
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• pp.191-202
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• 2021

Purpose: A near-infrared (NIR) fluorescence imaging is a promising tool for cancer-specific image guided surgery. Human epidermal receptor 2 (HER2) is one of the candidate markers for gastric cancer. In this study, we aimed to synthesize HER2-specific NIR fluorescence probes and evaluate their applicability in cancer-specific image-guided surgeries using an animal model. Materials and Methods: An NIR dye emitting light at 800 nm (IRDye800CW; Li-COR) was conjugated to trastuzumab and an HER2-specific affibody using a click mechanism. HER2 affinity was assessed using surface plasmon resonance. Gastric cancer cell lines (NCI-N87 and SNU-601) were subcutaneously implanted into female BALB/c nu (6-8 weeks old) mice. After intravenous injection of the probes, biodistribution and fluorescence signal intensity were measured using Lumina II (Perkin Elmer) and a laparoscopic NIR camera (InTheSmart). Results: Trastuzumab-IRDye800CW exhibited high affinity for HER2 (K_D=2.093(3) pM). Fluorescence signals in the liver and spleen were the highest at 24 hours post injection, while the signal in HER2-positive tumor cells increased until 72 hours, as assessed using the Lumina II system. The signal corresponding to the tumor was visually identified and clearly differentiated from the liver after 72 hours using a laparoscopic NIR camera. Affibody-IRDye800CW also exhibited high affinity for HER2 (K_D=4.71 nM); however, the signal was not identified in the tumor, probably owing to rapid renal clearance. Conclusions: Trastuzumab-IRDye800CW may be used as a potential NIR probe that can be injected 2-3 days before surgery to obtain high HER2-specific signal and contrast. Affibody-based NIR probes may require modifications to enhance mobilization to the tumor site.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.48.1-48.21
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• 2023

Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways. Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSC^BMP2) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSC^BMP2 were associated with migration and growth. MSC^BMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSC^BMP2. MSC^BMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3⁺CD25⁺ Treg of CD4⁺ cells were further increased in ALI mice treated with MSC^BMP2. In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSC^BMP2. Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSC^BMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.

• Journal of Chest Surgery
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• v.29 no.5
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• pp.542-547
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• 1996

All patients who underwent video-assisted thoracic surgery (VATS) for diagnostic purposes from Jan. 1992 to Aug. 1995 were reviewed. The total number of patients were 111 with 57 male and 54 female, and the mean age was 49 years (range 1 to 74). Multiple biopsies from more than one location were performed in 17 patients , pleural biopsies were performed In 49 patients, lung biopsies in 43 patients, mediastinal mass or Iymph node biopsies in 33 patients, and two pericardium biopsies and one dia- phragm biopsy, for a total of 128 biopsies. Seventeen pleural biopsy cases and one lung biopsy case underwent operation under local anesthesia , the rest were performed under general anesthesia. In patients who underwent lung biopsy, the mean age was 49.1 ye rs (range 22~ 73). The operating time was 40 to 170 minutes (mean 97), intravenous or intramuscular injection for pain control was required 0 to 22 times(mean 4.7), and chest tube was inserted from 1 to 26 days(mean 7). In all patients except two, a diagnosis was obtained from the biopsy and complication was encountered in one patient in whom intraoperative paroxysmal atrial tachycardia was detected. In 7 patients, a thorn- cotomy had to be done due to pleural adhesion or intraoperative bleeding, and 7 patients had postoperative complications associated with the chest tube. In the pleural biopsy group, the mean age was 49 years (range 17~ 74). The operating time was 25 to 80 minutes (mean 49), intravenous or intramuscular injection for pain control was needed 0 to 20 times (mean 3.6), and the chest tube was i.nserted for 0 to 67 days(mean 9.8). In all the patients, a diagnosis was possible. The chest tube was inserted for longer than 7 days in 11 patients. In the Iymph node biopsy roup, the mean age was 44.2 years (range 1 ~ 68). The operating time was )0 to 3)5 minutes(mean 105), pain control was required 0 to 15 times(mean 3.2), and a chest tube was kept in place for 1 to 36 days(mean 6.1). In one patient, a diagnosis was not possible and a chest tube was kept in place for longer than 7 days in 7 patients. In the multiple biopsy group, the mean age was 53.1 years(range 20~ 71). The operating time was 15 to 165 minutes(mean 85), and pain control was done from 0 to 17 times(mean 3.1). The chest tube was kept in place for 1 to 16 days (mean 7.9).

• Journal of the Korean Orthopaedic Association
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• v.54 no.5
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• pp.411-417
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• 2019

Purpose: To compare the clinical outcomes of single injection adductor canal block (SACB), continuous adductor canal block (CACB), and the concomitant use of transdermal buprenorphine after total knee arthroplasty (TKA). Materials and Methods: A total of 125 patients who underwent TKA were divided into three groups and the clinical results were retrospecitively compared. Group I was comprised of patients with pain controlled by SACB (n=41). Group II consisted of patients with pain controlled by both SACB and transdermal buprenorphine (10 ㎍/h) (n=44). Group III contained patients with pain controlled by CACB (n=40). The visual analogue scale (VAS) was used as the pain control indicator and the patients were measured on a VAS for resting on the bed (VAS-Rest) at 12 hours, 24 hours, and 48 hours after surgery. The VAS while doing continuous passive motion (VAS-CPM) on the first and second postoperative day was also measured. In addition, the total amount of medications used (Butopahn, Tridol, and Ketorac) for the intravenous patient controlled analgesia (PCA) was counted for 48 hours after surgery. As the indicator of the functional recovery outcome, the incidence of nausea and vomiting was observed for 48 hours after surgery. The maximum knee joint flexion range and maximum walking distance on the first and second postoperative day, and the total length of stay at the hospital were compared. Results: The VAS-Rest was similar in the three groups at 12 hours after surgery, but at 24 hours and 48 hours after surgery, group II and III a lower VAS-CPM and total amount of medications used for PCA than group I (p<0.05). The three groups showed a low incidence of nausea and vomiting, maximum knee joint flexion range, and similar walking distance and total length of stay at the hospital. Conclusion: The combination of SACB and transdermal buprenorphine has great pain control effect initially. On the other hand, it is not associated with catheter complications and it is convenient to use and safety toward the renal function. Therefore, the concomitant use of SACB and transdermal buprenorphine can be an effective pain control method after TKA.

• The Korean Journal of Nuclear Medicine Technology
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• v.16 no.1
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• pp.80-85
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• 2012

Purpose: The whole body bone scan is an examination that visualizing physiological change of bones and using bone-congenial radiopharmaceutical. The patients are intravenous injected radiopharmaceutical which labeled with radioactive isotope ($^{99m}Tc$) emitting 140 keV gammarays and scanned after injection. The 3 principles of radiation protection from external exposureare time, distance and shielding. On the 3 principles of radiation protection basis, radiopharmaceutical might just as well be injected rapidly for reducing radiation because it might be the unopened radiation source. However the radiopharmaceuticals are injected into patient directly and there is a limitation of distance control. This study confirmed the change of radiation exposure as change of distance from radiopharmaceutical and observed the change of radiation exposure afte rsetting a shelter for help to control radio-technician's exposure. Materials & methods: For calculate the average of injection time, the trained injector measured the injection time for 50 times and calculated the average (2 minutes). We made a source as filled the 99mTc-HDP 925 MBq 0.2 mL in a 1 mL syringe and measured the radiation exposure from 50 cm,100 cm,150 cm and 200 cm by using Geiger-Mueller counter (FH-40, Thermo Scientific, USA). Then we settled a lead shielding (lead equivalent 6 mm) from the source 25 cm distance and measured the radiation exposure from 50 cm distance. For verify the reproducibility, the measurement was done among 20 times. The correlation between before and after shielding was verified by using SPSS (ver. 18) as paired t-test. Results: The radiation doses according to distance during 2 minutes from the source without shielding were $1.986{\pm}0.052{\mu}$ Sv in 50 cm, $0.515{\pm}0.022{\mu}$ Sv in 100 cm, $0.251{\pm}0.012{\mu}$ Sv in 150 cm, $0.148{\pm}0.006{\mu}$ Sv in 200 cm. After setting the shielding, the radiation dose was $0.035{\pm}0.003{\mu}$ Sv. Therefore, there was a statistical significant difference between the radiation doses with shielding and without shielding ($p$<0.001). Conclusion: Because the great importance of whole body bone scan in the nuclear medicine, we should make an effort to reduce radiation exposure during radiopharmaceutical injections by referring the principles of radiation protection from external exposure. However there is a limitation of distance for direct injection and time for patients having attenuated tubules. We confirmed the reduction of radiation exposure by increasing distance. In case of setting shield from source 25 cm away, we confirmed reducing of radiation exposure. Therefore it would be better for reducing of radiation exposure to using shield during radiopharmaceutical injection.

• Journal of Embryo Transfer
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• v.19 no.2
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• pp.81-87
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• 2004

This study was designed to determine whether repeated superovulation is beneficial for recovery and quality of oocytes in Korean native goats. Seventy-six mature goats, maintained in a pen under natural day length and fed hay ad libitum, were pretreated with progestagen impregnated CIDR for 10 days and then the goats were divided into two groups. One group of the goats received a single intramuscular injection of 1,000 IU PMSG on Day 8 of CIDR insertion. The other group of the goats received twice daily intramuscular injections of a total of 70 mg FSH for 3 days from Day 8 of CIDR. All the gonadotropin treated goats were injected with 10 mg $PGF2{\alpha}on$ Day 8 and 400 IU hCG in the afternoon on Day 10. For oocyte recovery, donor goats were fasted 24 h before operation. Anesthesia was induced by intravenous injection of 2% xylazine(0.2 mg/kg body weight) and ketamin(11 mg/kg body weight). In vivo oocytes were recovered by follicle aspiration or oviduct flushing at 35 to 40 hours after hCG injection through mid-ventral incision. The mean number of CL and oocytes recovered and recovery rate of oocytes by oviduct flushing were greater(P<0.05) in the first treatment than those in the second treatment. Contrary to our assumption, PMSG treatment significantly (P<0.05) increased the number of CL formed and recovery rate of oocytes compared to FSH. However, the same effect was not observed in recovery of follicular oocytes. There was no significant difference in oocyte quality between FSH and PMSG or first and second treatments. The present results indicate that repeated superovulation and repeated use of donor animals may be inefficient for obtaining oocytes in good qualities.

• Journal of Embryo Transfer
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• v.19 no.2
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• pp.113-119
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• 2004

The purpose of the present study was to examine whether collection time affects results of oocyte recovery from superovulated goats. Fiftyty-one mature Korean native goats, maintained in a pen under natural day length and fed hay ad libitum, were pretreated with progestagen impregnated CIDR for 10 days and then the goats were divided into two groups. One group of the goats received a single intramuscular injection of 1,000 IU PMSG on Day 8 of CIDR insertion. The other group of the goats received twice daily intramuscular injections of a total of 70 mg FSH for 3 days from Day 8 of CIDR. All the gonadotropin treated goats were injected with 10 mg $PGF_{2\alpha}$ on Day 8 and 400 IU hCG in the afternoon on Day 10. For oocyte recovery, donor goats were fasted 24 h before operation. Anesthesia was induced by intravenous injection of 2% xylazine(0.2 mg/kg body weight) and ketamin(11 mg/kg body weight). In vivo oocytes were recovered by follicle aspiration or oviduct flushing at 29 to 34, 35 to 40 and 41 to 50 h after hCG injection through mid-ventral incision. There was no significant difference in the mean number of CL and oocytes recovered. Oocyte collection at 29 to 40 h after hCG increased(P<0.05) the recovery rate of ovulated oocytes in oviducts compared to 41 to 50 h. The same results were also observed in the recovery of follicular oocytes. Oocyte grade was not affected by collection time. When oocytes were collected from follicular oocytes at 41 to 50 h after hCG, the recovery rate of Grade II oocytes was the lowest(P<0.05). From these results, it is suggested that oocyte recovery at 35 to 40 h after hCG will be successful for further use.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.5
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• pp.263-270
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• 2006

Purpose: Several radioisotope-labeled thymidine derivatives such as $[^{11}C]$thymidine was developed to demonstrate cell proliferation in tumor. But it is difficult to track metabolism with $[^{11}C]$thymidine due to rapid in vivo degradation and its short physical half-life. 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT) was reported to have the longer half life of fluorine-18 and the lack of metabolic degradation in vivo. Here, we described the synthesis of the 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT) and compared with $([^{18}F]FET)\;and\;([^{18}F]FDG)$ in cultured 9L cell and obtained the biodistribution and PET image in 9L tumor hearing rats. Material and Methods: For the synthesis of $[^{18}F]$FLT, 3-N-tert-butoxycarbonyl-(5'-O-(4,4'-dimet hoxytriphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-${\beta}$-D-threopentofuranosyl)thymine was used as a FLT precursor, on which the tert-butyloxycarbonyl group was introduced to protect N3-position and nitrobenzenesulfonyl group. Radiolabeling of nosyl substitued precursor with $^{18}F$ was performed in acetonitrile at $120^{\circ}C$ and deproteced with 0.5 N HCI. The cell uptake was measured in cultured 9L glioma cell. The biodistribution was evaluated in 9L tumor bearing rats after intravenous injection at 10 min, 30 min, 60 min and 120 min and obtained PET image 60 minutes after injection. Results: The radiochemical yield was about 20-30% and radiochemical purity was more than 95% after HPLC purification. Cellular uptake of $[^{18}F]$FLT was increased as time elapsed. At 120 min post-injection, the ratios of tumor/blood, tumor/muscle and tumor/brain were $1.61{\pm}0.34,\;1.70{\pm}0.30\;and\;9.33{\pm}2.22$, respectively. The 9L tumor was well visualized at 60 min post injection in PET image. Conclusion: The uptake of $[^{18}F]$FLT in tumor was higher than in normal brain and PET image of $[^{18}F]$FLT was acceptable. These results suggest the possibility of $[^{18}F]$FLT at an imaging agent for brain tumor.

• Journal of Chest Surgery
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• v.36 no.7
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• pp.518-522
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• 2003

Left ventricular thrombosis is a frequent and potentially dangerous complication in acute myocardiac infarction, but its occurrence and adequate therapy has not been known in patients with Dor procedure for the ischemic cardiomyopathy. We report a patient, 45 year-old male, who had a new left ventricular thrombus developed after coronary arterial bypass graft, Dor procedure, and removal of the left ventricular thrombus for ischemic car-diomyopathy. Left ventricular thrombus was disappeared on the follow-up cardiac MRI following intravenous heparin injection and oral coumadin therapy. This case suggest that anticoagulation therapy may prevent patients with the severe left ventricular dysfunction and apical aneurysm and dyskinesia from developing the left ventricular thrombus, and that thrombi will resolve without clinical evidence of systemic embolism.

• Biomolecules & Therapeutics
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• v.18 no.2
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• pp.205-210
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• 2010

Several studies have shown that plant-derived polyphenols reduce cardiovascular accidents in high-risk patients and the inhibition of platelet function may be responsible for part of this benefit. Lindera obtusiloba is widely used in traditional herbal medicine for the treatment of cardiovascular and inflammatory diseases. Therefore, the antiplatelet and antithrombotic activities of Lindera obtusiloba Extracts (LOE) on in vitro platelet aggregation, radical scavenging activity and in vivo murine pulmonary thrombosis were examined. LOE was able to directly scavenge the stable DPPH radical in a concentration-dependent manner and its $IC_{50}$ value was 3.9 ${\pm}$ 0.1 ${\mu}g$/ml. LOE significantly inhibited collagen- and ADP-induced platelet aggregation in a concentration-dependent manner and its $IC_{50}$ value is 0.9 ${\pm}$ 0.1 mg/ml and 0.4 ${\pm}$ 0.1 mg/ml respectively. The inhibitory effect of LOE was comparable to aspirin ($IC_{50}$ values were 1.0 ${\pm}$ 0.5 and 1.0 ${\pm}$ 0.7 mg/ml, respectively). Furthermore, oral administration of LOE suppressed the death of mice with pulmonary thrombosis induced by intravenous injection of collagen plus epinephrine. Taken together, our results suggest LOE may be a promising candidate for antithrombotic agent, and the antithrombotic effect of LOE may be due to, at least in part, antiplatelet activity.