Lee, Sung Yong;Lee, Ju Han;Jung, Jin Yong;Lee, Kyoung Ju;Lee, Seung Hyeun;Kim, Se Joong;Lee, Eun Joo;Hur, Gyu Young;Jung, Ki Hwan;Jung, Hye Cheol;Lee, Sang Yeub;Kim, Je Hyeong;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa
Tuberculosis and Respiratory Diseases
/
v.58
no.5
/
pp.473-479
/
2005
Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.
Lee, Nuri;Kim, Tae Yoon;Kang, Dong Yun;Choi, Jae Hyock;Jeong, Jong Hwi;Shin, Dongho;Lim, Young Kyung;Park, Jeonghoon;Kim, Tae Hyun;Lee, Se Byeong
Progress in Medical Physics
/
v.26
no.4
/
pp.250-257
/
2015
Multi-leaf collimator (MLC) systems are frequently used to deliver photon-based radiation, and allow conformal shaping of treatment beams. Many proton beam centers currently make use of aperture and snout systems, which involve use of a snout to shape and focus the proton beam, a brass aperture to modify field shape, and an acrylic compensator to modulate depth. However, it needs a lot of time and cost of preparing treatment, therefore, we developed the manual MLC for solving this problem. This study was carried out with the intent of designing an MLC system as an alternative to an aperture block system. Radio-activation and dose due to primary proton beam leakage and the presence of secondary neutrons were taken into account during these iterations. Analytical calculations were used to study the effects of leaf material on activation. We have fabricated tray model for adoption with a wobbling snout ($30{\times}40cm^2$) system which used uniform scanning beam. We designed the manual MLC and tray and can reduce the cost and time for treatment. After leakage test of new tray, we upgrade the tray with brass and made the safety tool. First, we have tested the radio-activation with usually brass and new brass for new manual MLC. It shows similar behavior and decay trend. In addition, we have measured the leakage test of a gantry with new tray and MLC tray, while we exposed the high energy with full modulation process on film dosimetry. The radiation leakage is less than 1%. From these results, we have developed the design of the tray and upgrade for safety. Through the radio-activation behavior, we figure out the proton beam leakage level of safety, where there detects the secondary particle, including neutron. After developing new design of the tray, it will be able to reduce the time and cost of proton treatment. Finally, we have applied in clinic test with original brass aperture and manual MLC and calculated the gamma index, 99.74% between them.
Although the outcome of cancer patients after cytotoxic chemotherapy is related diverse mechanisms, multidrug resistance (MDR) for chemotherapeutic drugs due to cellular P-glycoprotein (Pgp) or multidrug-resistance associated protein (MRP) is most important factor in the chemotherapy failure to cancer. A large number of pharmacologic compounds, including verapamil, quinidine, tamoxifen, cyclosporin A and quinolone derivatives have been reported to overcome MDR. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transporter. $^{99m}Tc$-MIBI and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of PgP-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and $N-[^{11}C]acetyl-leukotriene$ E4 provides an opportunity to study MRP function non-invasively in vivo. SPECT and PET pharmaceuticals have successfully used to evaluate pharmacologic effects of MDR modulators. Imaging of MDR and reversal of MDR with bioluminescence in a living animal is also evaluated for future clinical trial. We have described recent advances in molecular imaging of MDR and reviewed recent publications regarding feasibility of SPECT and PET imaging to study the functionality of MDR transporters in vivo.
Polyamines are essential for cell growth and differentiation; however their precise roles are unclear yet. In the present study, the cytotoxic effect of spermine (spm) on MCF-7 cells was investigated. In the MTT assay of MCF-7 cells treated with spm, cell viability was significantly decreased in a time-and dose-dependent manner. Cell viability measurement was confirmed by trypan blue staining. FACS analysis shows that sub-G1 was increased in a time-and dose-dependent manner too. When the cells were treated with spm, cells started to show morphological changes within 2 hrs. The expression of adhesion proteins (FAK and integrin ${\beta}1$), and cytoskeletal protein (actin) was checked by Western blotting analysis. Integrin ${\beta}1$ levels were slightly decreased, and FAK and actin levels were rapidly decreased with spm treatment. In confocal laser scanning microscopy, the distribution of actin did not change but the expression decreased in a dose-dependent manner with spm treatment. FAK was evenly distributed under the plasma membrane in the untreated control. However, at 10 ${\mu}M$ spm FAK seemed to move toward the cell nucleus. Integrin ${\beta}1$, which was mainly found in the focal point of the plasma membrane in the untreated control, dispersed through the entire plasma membrane in spm treatment. The present results indicate that cytotoxic effects of spm are triggered by the disruption of adhesion proteins and cytoskeletal protein.
Kim, Yun-Kyung;Choi, Ja-Hyeong;Lee, Hyun-Jung;Son, Yoo-Jin;Yoon, So-Yeong;Lee, Jung-Hwa;Lee, Min-Kyung
Journal of dental hygiene science
/
v.15
no.4
/
pp.424-429
/
2015
The aim of this study was to investigate whether peripheral or central administration of triptolide is involved in pain modulation in inflammatory orofacial pain. The inflammatory orofacial pain was induced by the injection of 5% formalin into right vibrissa pad of rats. The pain behavioral response was measured the number of grooming or scratching on the orofacial area for 9 successive 5 minutes intervals. Triptolide was administrated into the identified vibrissa pad (12.5, 25, $50{\mu}g/50{\mu}l$) or intracisternal space (0.01, 0.1, $1{\mu}g/10{\mu}l$) 10 min before formalin injection. The nociceptive responses were reduced in the 2nd phase (11~45 minutes), particularly 20, 30 minutes after fomalin injection following administration of triptolide into vibrissa pad (25, $50{\mu}g/50{\mu}l$). Intracisternal ($1{\mu}g/10{\mu}l$) administration of triptolide alleviated the formalin-induced pain behaviors in the 2nd phase, especially 25~40 minutes after formalin injection. Triptolide could be a promising analgesic agent in the treatment of inflammatory orofacial pain.
Heat manipulation at early age has been known to help chickens cope with heat stress later in life. The present study was conducted to determine the effects of early heat conditioning at 5 days of age on performance in broilers when re-exposed to heat stress later in life. Day-old, 256 Arbor Acre boiler chicks were housed in two identical rooms where all broilers were exposed to a 23-h light: 1-h dark cycle throughout the study and provided with feed and water ad libitum. At the age of 5 days, one group was exposed to $37^{\circ}C$ for 24 hours and then returned to the temperature at which control birds were maintained (early heat condition group) while the other was maintained without heat modulation (Control). On 21 days, broilers were regrouped into 4 groups (CON+CON: control+control; CON+HS: control+heat stress; HC+CON: heat conditioning+control; HC+HS: heat conditioning+heat stress), and given 7 days for adaptation. On 28 days, birds in one room were exposed to heat stress ($21^{\circ}C{\rightarrow}31^{\circ}C$) for 3 days whereas those in the other were at room temperature. Heat stress resulted in decreased feed intake, water intake, and body weight gain (P<0.05), but increased rectal temperature and mortality (P<0.05). No beneficial effects of heat conditioning were detected when broilers were exposed to heat stress again at later in life. The present results were discussed together with other studies regarding possible differences in methods such as ages of breeders and strains, which may have resulted in the failure of heat conditioning to help broilers resist heat stress.
Purpose Proton therapy can deliver an optimal dose to tumor while reducing unnecessary dose to normal tissue as compared the conventional photon therapy. As proton beams are irradiated into tissue, various positron emitters are produced via nuclear fragmentation reactions. These positron emitters could be used for the dose verification by using PET. However, the short half-life of the radioisotopes makes it hard to obtain the enough amounts of events. The aim of this study is to investigate the effect of off-line PET imaging scan time on the PET image quality. Materials and Methods The various diameters of spheres (D=37, 28, 22 mm) filled with distilled water were inserted in a 2001 IEC body phantom. Then proton beams (100 MU) were irradiated into the center of the each sphere using the wobbling technique with the gantry angle of $0^{\circ}$. The modulation widths of the spread out bragg peak were 16.4, 14.7 and 9.3 cm for the spheres of 37, 28 and 22 mm in diameters respectively. After 5 min of the proton irradiation, the PET images of the IEC body phantom were obtained for 50 min. The PET images with different time courses (0-10 min, 11-20 min, 21-30 min, 31-40 min and 41-50 min) were obtained by dividing the frame with a duration of 10 min. In order to evaluate the off-line PET image quality with the different time courses, the contrast-to-noise ratio (CNR) of the PET image calculated for each sphere. Results The CNRs of the sphere (D=37 mm) were 0.43, 0.42, 0.40, 0.31 and 0.21 for the time courses of 0-10 min, 11-20 min, 21-30 min, 31-40 min and 41-50 min respectively. The CNRs of the sphere (D=28 mm) were 0.36, 0.32, 0.27, 0.19 and 0.09 for the time courses of 0-10 min, 11-20 min, 21-30 min, 31-40 min and 41-50 min respectively. The CNR of 37 mm sphere was decreased rapidly after 30 min of the proton irradiation. In case of the spheres of 28 mm and 22 mm, the CNR was decreased drastically after 20 min of the irradiation. Conclusion The off-line PET imaging time is an important factor for the monitoring of the proton therapy. In case of the lesion diameter of 22 mm, the off-line PET image should be obtained within 25 min after the proton irradiation. When it comes to small size of tumor, the long PET imaging time will be beneficial for the proton therapy treatment monitoring.
Jae-Sook RYU;Ryung CHOI;So-Young PARK;Hyun PARK;Duk-Young MIN
Parasites, Hosts and Diseases
/
v.36
no.4
/
pp.255-260
/
1998
To evaluate the biological and biochemical characteristics of Trichomonas vaginalis KT9 isolate, the growth and size of trichomonads, pathogenicity in mouse, protein profiles and proteinase activity were examined after shifting the medium from TPS-1 into TYM. Generation time of trichomonads in TYM medium was 4.5 hr in comparison to TPS-1 with 7.1 hr. Size of trichomonads cultured in TPS-1 medium ($8.5{\;}{\pm}{\;}0.9{\;}{\times}{\;}6.0{\;}{\pm}{\;}0.9{\;}{\mu\textrm{m}}$) was significantly smaller than those in TYM medium ($10.9{\;}{\pm}{\;}1.4{\;}{\times}{\;}8.2{\;}{\pm}{\;}0.9{\;}{\mu\textrm{m}}$). Trichomonads cultured in TYM medium produced subcutaneous abscess in 9 out of 10 mice, whereas those in TPS-1 medium produced abscesses in 2 out of 10 mice. In SDS-PAGE, trichomonad Iysates from both media showed ten common bands. However, trichomonads in TYM medium showed additional bands of 136 kDa, 116 kDa and 40 kDa in comparison to those in TPS-1 with 100 kDa. By immunoblot with T. vaginalis-immunized rabbit sera, T. vaginalis cultivated in both TYM and TPS-1 media showed 5 common bands. and unique bands of 116 kDa. 105 kDa. and 86 kDa were observed in trichomonads in TYM while a 140 kDa band in those in TPS-1. In gelatin SDS-PAGE, trichomonads in TYM degraded gelatin stronger than those in TPS-1. Also protease activity of trichomonads in TYM was significantly higher than that of trichomonads in TPS-1 using Bz-Pro-Phe-Arg-Nan as a substrate. According to the results, it is assumed that the shift from TPS-1 into TYM medium for cultivation of T. vaginalis might modulate the biological and biochemical properties of T vaginalis in vitro.
For the enhancement of ginsenoside production in hairy roots cultures of Panax ginseng, the uptake rate of inorganic elements and ginsenoside contents were investigated by different concentrations of about phosphorus (P $O_{4}$$^{[-10]}$ ) and nitrogen (N $H_{4}$$^{+}$, N $O_{3}$$^{[-10]}$ ) sources. According to increased phosphorus and nitrogen sources, the uptake rate of $Mg^{2+}$ and F $e^{2+}$ in ginseng hairy roots were significantly increased. The uptake rate of F $e^{2+}$ in 5.15 mM N $H_{4}$$^{+}$ was higher at 47.5% than that in 20.6 mM, whereas that of C $u^{2+}$ in 10.3 mM were higher at 123.1% than that in 41.2 mM. These results indicated that phosphorus and nitrogen sources act not only elevated growth of hairy roots but also the uptake-enhancement of the irons and other ions. The optimum concentration of phosphorus and nitrogen sources for the contents of free sugars were different to kinds of free sugars. The optimum concentration of phosphorus and nitrogen sources for the ginsenoside formation in ginseng hairy roots cultures were highest at the most low concentration of all. The contents of ginsenoside-R $b_2$and -Rc in 0.31 mM P $O_{4}$$^{[-10]}$ were increased to 44.7% and 29.9% than that in 0.62 mM P $O_{4}$$^{[-10]}$ , respectively. The contents of ginsenoside-R $b_2$ and -Rc in 5.15 mM N $H_{4}$$^{+}$ were increased to 21.7% and 31.9% than that in 10.30 mM N $H_{4}$$^{+}$, respectively. The contents of ginsenoside-R $b_2$and -Rc in 4.7 mn N $O_{3}$$^{[-10]}$ were also increased to 17.6% and 25.5% than that in 9.4 mM N $O_{3}$$^{[-10]}$ , respectively. These results indicate that enhancement of the ginsenoside formation in ginseng hairy roots was feasible by new medium modulation of concentration of phosphorus and nitrogen sources.rogen sources.
Kim, Il-Du;Woo, Young-Yun;Hong, Sung-Chul;Kim, Jang-Heon;Moon, Jung-Hwan;Jun, Myoung-Su;Kim, Jung-Joon;Kim, Bum-Man
The Journal of Korean Institute of Electromagnetic Engineering and Science
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v.18
no.8
/
pp.880-886
/
2007
We have proposed a new "hybrid" envelope elimination and restoration(EER) transmitter architecture using an efficiency optimized power amplifier(PA) and modified bias modulator. The efficiency of the PA at the average drain voltage is very important for the overall transmitter efficiency because the PA operates mostly at the average power region of the modulation signal. Accordingly, the efficiency of the PA has been optimized at the region. Besides, the bias modulator has been accompanied with the emitter follower for the minimization of memory effect. A saturation amplifier, class $F^{-1}$ is built using a 5-W PEP LDMOSFET for forward-link single-carrier wideband code-division multiple-access(WCDMA) at 1-GHz. For the interlock experiment, the bias modulator has been built with the efficiency of 64.16% and peak output voltage of 31.8 V. The transmitter with the proposed PA and bias modulator has been achieved an efficiency of 44.19%, an improvement of 8.11%. Besides, the output power is enhanced to 32.33 dBm due to the class F operation and the PAE is 38.28% with ACLRs of -35.9 dBc at 5-MHz offset. These results show that the proposed architecture is a very good candidate for the linear and efficient high power transmitter.
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