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Evaluation of response to stereotactic radiosurgery in patients with radioresistant brain metastases

  • Sayan, Mutlay;Mustafayev, Teuta Zoto;Sahin, Bilgehan;Kefelioglu, Erva Seyma Sare;Wang, Shang-Jui;Kurup, Varsha;Balmuk, Aykut;Gungor, Gorkem;Ohri, Nisha;Weiner, Joseph;Ozyar, Enis;Atalar, Banu
    • Radiation Oncology Journal
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    • v.37 no.4
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    • pp.265-270
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    • 2019
  • Purpose: Renal cell carcinoma (RCC) and melanoma have been considered 'radioresistant' due to the fact that they do not respond to conventionally fractionated radiation therapy. Stereotactic radiosurgery (SRS) provides high-dose radiation to a defined target volume and a limited number of studies have suggested the potential effectiveness of SRS in radioresistant histologies. We sought to determine the effectiveness of SRS for the treatment of patients with radioresistant brain metastases. Materials and Methods: We performed a retrospective review of our institutional database to identify patients with RCC or melanoma brain metastases treated with SRS. Treatment response were determined in accordance with the Response Evaluation Criteria in Solid Tumors. Results: We identified 53 radioresistant brain metastases (28% RCC and 72% melanoma) treated in 18 patients. The mean target volume and coverage was 6.2 ± 9.5 mL and 95.5% ± 2.9%, respectively. The mean prescription dose was 20 ± 4.9 Gy. Forty lesions (75%) demonstrated a complete/partial response and 13 lesions (24%) with progressive/stable disease. Smaller target volume (p < 0.001), larger SRS dose (p < 0.001), and coverage (p = 0.008) were found to be positive predictors of complete response to SRS. Conclusion: SRS is an effective management option with up to 75% response rate for radioresistant brain metastases. Tumor volume and radiation dose are predictors of response and can be used to guide the decision-making for patients with radioresistant brain metastases.

Semaphoring mAb: a New Guide in RIT in Inhibiting the Proliferation of Human Skin Carcinoma

  • Liu, Yuan;Ma, Jing-Yue;Luo, Su-Ju;Sun, Chen-Wei;Shao, Li-Li;Liu, Quan-Zhong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.941-945
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    • 2015
  • Semaphoring is a transmembrane receptor which participates in many cytokine-mediated signal pathways that are closely related to the angiogenesis, occurrence and development of carcinoma. The present study was designed to access the effect of mono-antibody (mAb) guided radioimmunotherapy (RIT) on skin carcinoma and investigate the potential mechanisms. Semaphoring mAb was acquired from mice (Balb/c), purified with rProtein A column; purity, concentration and activity were tested with SDS-PAGE and indirect ELISA; specificity and expression on the cutanuem carcinoma line and tissue were tested by Western blotting; morphology change was assessed by microscopy. MTT assay and colony inhibition tests were carried out to test the influence on the proliferation of tumor cells; Western blotting was also carried out for expression of apoptosis-associated (caspase-3, Bax, Bcl-2) and proliferation-related (PI3K, p-Akt, Akt, p-ERK1/2, ERK1/2) proteins and analyse the change in signal pathways (PI3K/Akt and MEK/ERK). The purity of purified semaphorin mAb was 96.5% and the titer is about $1{\times}10^6$. Western blotting showed semaphoring mAb to have specifically binding stripes with semaphoring b1b2 protein, B16F10, and A431 cells at 39KDa, 100KDa and 130KDa, respectively. Positive expression was detected both in cutanuem carcinoma line and tissue and it mostly located in cell membranes. MMT assay revealed dose-relate and time-relate inhibitory effect of semaphorin mAb on A431 and B16F10. Colony inhibition tests also showed dose-relate inhibitory effects. Western blotting demonstrated the expression of apoptosis and proliferation-related protein and changes in signal pathway. In conclusion, we demonstrated that semaphorin is highly expressed on the tumor cell-surfaces and RIT with semaphorin mAb has effect in i nhibiting proliferation and accelerating apoptosis of tumor cells.

Pro-Apoptotic Activity of 4-Isopropyl-2-(1-Phenylethyl) Aniline Isolated from Cordyceps bassiana

  • Kim, Mi Seon;Lee, Yunmi;Sung, Gi-Ho;Kim, Ji Hye;Park, Jae Gwang;Kim, Han Gyung;Baek, Kwang Soo;Cho, Jae Han;Han, Jaegu;Lee, Kang-Hyo;Hong, Sungyoul;Kim, Jong-Hoon;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • v.23 no.4
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    • pp.367-373
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    • 2015
  • Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4-isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti-cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full-length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent.

The effect of nanoemulsified methionine and cysteine on the in vitro expression of casein in bovine mammary epithelial cells

  • Kim, Tae-Il;Kim, Tae-Gyun;Lim, Dong-Hyun;Kim, Sang-Bum;Park, Seong-Min;Lim, Hyun-Joo;Kim, Hyun-Jong;Ki, Kwang-Seok;Kwon, Eung-Gi;Kim, Young-Jun;Mayakrishnan, Vijayakumar
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.2
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    • pp.257-264
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    • 2019
  • Objective: Dairy cattle nutrient requirement systems acknowledge amino acid (AAs) requirements in aggregate as metabolizable protein (MP) and assume fixed efficiencies of MP used for milk protein. Regulation of mammary protein synthesis may be associated with AA input and milk protein output. The aim of this study was to evaluate the effect of nanoemulsified methionine and cysteine on the in-vitro expression of milk protein (casein) in bovine mammary epithelial cells (MAC-T cells). Methods: Methionine and cysteine were nonionized using Lipoid S 75 by high-speed homogenizer. The nanoemulsified AA particle size and polydispersity index were determined by dynamic light scattering correlation spectroscopy using a high-performance particle sizer instrument. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to determine the cytotoxicity effect of AAs with and without nanoionization at various concentrations (100 to $500{\mu}g/mL$) in mammary epithelial cells. MAC-T cells were subjected to 100% of free AA and nanoemulsified AA concentration in Dulbecco's modified Eagle medium/nutrient mixture F-12 (DMEM/F12) for the analysis of milk protein (casein) expression by the quantitative reverse transcription polymerase chain reaction method. Results: The AA-treated cells showed that cell viability tended to decrease (80%) in proportion to the concentration before nanogenesis, but cell viability increased as much as 90% after nanogenesis. The analysis of the expression of genetic markers related to milk protein indicated that; ${\alpha}_{s2}$-casein increased 2-fold, ${\kappa}$-casein increased 5-fold, and the amount of unchanged ${\beta}$-casein expression was nearly doubled in the nanoemulsified methionine-treated group when compared with the free-nanoemulsified methionine-supplemented group. On the contrary, the non-emulsified cysteine-administered group showed higher expression of genetic markers related to milk protein ${\alpha}_{s2}$-casein, ${\kappa}$-casein, and ${\beta}$-casein, but all the genetic markers related to milk protein decreased significantly after nanoemulsification. Conclusion: Detailed knowledge of factors, such nanogenesis of methionine, associated with increasing cysteine and decreasing production of genetic markers related to milk protein (casein) will help guide future recommendations to producers for maximizing milk yield with a high level of milk protein casein.

EXPRESSION OF OSTEOGENESIS RELATED FACTORS ACCORDING TO DISTRACTION RATE IN THE DISTRACTION OSTEOGENESIS (신연 골형성술시 신연속도에 따른 골형성 관여 인자의 발현)

  • Jee, Yu-Jin;Kim, Yeo-Gab
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.34 no.3
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    • pp.250-265
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    • 2008
  • Distraction osteogenesis is a well-established clinical treatment for limb length discrepancy and skeletal deformities. Appropriate mechanical tension-stress is believed not to break the callus but rather to stimulate osteogenesis. In contrast to fracture healing, the mode of bone formation in distraction osteogenesis is primarily intramembranous ossification. Although the biomechanical, histological, and ultrastructural changes associated with distraction osteogenesis have been widely described, the basic biology of the process is still not well known. Moreover, the molecular mechanisms in distraction osteogenesis remain largely unclear. Recent studies have implicated the growth factor cascade is likely to play an important role in distraction. And current reserch suggested that mechanical tension-stress modulates cell shape and phenotype, and stimulates the expression of the mRNA for bone matrix proteins. The purpose of this study is to examine the pattern of expression of growth factors($TGF-{\beta}1$, IGF-I, bFGF) and extracellular matrix proteins(osteoclacin, osteonectin) related to osteogenesis by osteodistraction of the mandible in rabbits. 24 rabbits is used for this experiment. Experimental group are gradual distraction(0.7mm, twice/day), acute distraction(1.4mm, twice/day) and control group is only osteotomized. After 5 days latency, osteotomic site is distracted for each 7 days and 3.5 days. Consolidation period is 28 days. The animal is sacrificed at the 3th, 7th, 14th, 28th. The distracted bone is examined by immunohistochemical analysis and RT-PCR analysis. The results obtained from this study were as follow : No significant difference was found on clinical examination according to distraction rate, but gradual distraction was shown to improve regenerate bone formation on radiographic and histologic examination. Growth factors and extracelluar matrix proteins expression increased in distraction group than control group. From these results, it could be stated that graudal distraction is shown to improve and accelerate bone formation and mechanical stress like distraction has considerable effects on osteogenesis related factors. And rabbit is the most appropriate animal model for further reseach on the molecular mechanisms that mediate osteodistraction. It is believed that understanding the biomolecular mechanisms that mediate distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone healing.

Rhinotomy for Chronic Rhinitis by Nasal Foreign Body in a Dog (비강 내 이물에 의한 만성 비염 치료를 위해 비강절개술 적용 증례)

  • Kim, Ji-Hye;Park, Jin-Uk;Kim, Jong-Min;Park, Seong-Kyu;Son, Jin-Na;Chang, Dong-Woo;Na, Ki-Jeong;Choi, Seok-Hwa;Kim, Gon-Hyung
    • Journal of Veterinary Clinics
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    • v.28 no.4
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    • pp.452-456
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    • 2011
  • 5 year-old female Siberian husky which was 27 kg had presented with a recurrent rhinitis with chronic discharge and cough. A nasal foreign material had been suggested by a finding of a bone density ($0.3{\times}0.3$ cm) in the left nasal cavity on X-ray and CT-scanning. Soft tissue opacity in frontal sinus and nasal cavity was increased and foreign material was located beside turbinate bone in the left nasal. We found that there was the increase in the number of eosinophil and mast cell by the nasal cytology test. These results mentioned above indicated that the rhinitis by nasal foreign body was suspicious. We decided that the transfrontal rhinotomy could be the proper procedure to approach the material in this case. After rhinotomy, the foreign body and severe sticky discharge were removed. Drain was placed through the hole and into the frontal sinus and nasal cavity which were flushed two times a day for 7 days. The clinical signs such as cough and nasal discharge were shown to be improved in the every visiting for the re-check. On the $40^{th}$ day after surgery, we could confirm that the most of soft tissue density in the frontal sinus and nasal cavity was decreased by CT-scanning. However, foreign body was not identified by histological examination. For the treatment of chronic rhinitis caused by foreign body, the surgical method such as rhinotomy can be applied, when it is difficult to remove it in the guide of the nasal endoscope.

Experimental Verification of a Liquid Damper with Changeable Natural Frequency for Building Response Control (고유진동수 조절이 가능한 액체댐퍼의 건물응답 제어실험)

  • Kim, Dong-Ik;Min, Kyung-Won;Park, Ji-Hun;Kim, Jae-Keon;Hwang, Kyu-Seok;Gil, Yong-Sik
    • Journal of the Computational Structural Engineering Institute of Korea
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    • v.25 no.4
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    • pp.323-330
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    • 2012
  • This study deals with the experiments of liquid dampers with multi cells whose vertical tubes are divided into several square columns for easily changing natural frequencies. Shaking table test is performed to verify control effectiveness of the dampers which are installed on a building structure. To design liquid dampers, a 64-story building structure is reduced to a SDOF structure with 1/20 of similitude laws based on acceleration. The structure model is made up to adjust its mass and stiffness easily, with separate mass and drive parts. Mass parts indicate real structure's weights and drive parts indicate real structure's stiffness with springs and LM guides. Manufactured liquid damper has 18 cells and its natural frequency ranges are 0.65Hz to 0.81Hz. Shaking table test is carried out with one way excitation to compare with only accelerations of a large-scale structure and a structure installed with liquid dampers. Control performance of the liquid damper is expressed by the transfer function from shaking table accelerations to the large-scale structure ones. Testing results show that the liquid damper reduced a large-scale structure's response by tuned natural frequencies.

Natural Origin Polymers: Applications as Wound Care Materials (자연 고분자 : 상처 치료 재료로 활용)

  • Karadeniz, Fatih;Sung, Hye Kyeong;Kim, Han Seong
    • Journal of Life Science
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    • v.29 no.3
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    • pp.382-393
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    • 2019
  • Wound care is a health industry concern affecting millions worldwide. Recent increase in metabolic disorders such as diabetes comes with elevated risk of wound-based complications. Treatment and management of wounds are difficult practices due to complexity of the wound healing process. Conventional wound dressings and treatment applications only provide limited benefits which are mainly aimed to keep wound protected from external factors. To improve wound care, recent developments make biopolymers to be of high interest and importance to researchers and medical practitioners. Biopolymers are polymers or natural origin produced by living organisms. They are credited to be highly biocompatible and biodegradable. Currently, studies reported biopolymers to exhibit various health beneficial properties such as antimicrobial, anti-inflammatory, hemostatic, cell proliferative and angiogenic activities which are crucial for effective wound management. Several biopolymers, namely chitosan, cellulose, collagen, hyaluronic acid and alginic acid have been already investigated and applied as wound dressing agents. Different derivatives of biopolymers have also been developed by cross-linking with other molecules, grafting with other polymers, and loading with bioactive agents or drugs which showed promising results towards wound healing without any undesired outcome such as scarring and physiological abnormalities. In this review, current applications of common biopolymers in wound treatment industry are highlighted to be a guide for further applications and studies.

Impact of Pre-planting NO3:NH4 Ratios in Root Media on the Growth of Tomato Plug Seedlings (혼합상토에 기비로 혼합된 NO3:NH4 비율이 토마토 플러그 묘 생장에 미치는 영향)

  • Sung, Jwa Kyung;Lee, Nu Ri;Choi, Jong Myung
    • Horticultural Science & Technology
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    • v.34 no.5
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    • pp.727-735
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    • 2016
  • This research was conducted to investigate the influence of various pre-planting $NO_3:NH_4$ ratios in the coir dust+peatmoss+perlite (3.5:3.5:3, v/v/v) medium on the growth of tomato plug seedlings (cv. Dotaerang Dia), changes in chemical properties of root media, and tissue nutrient contents. With the fixation of N concentration to $300mg{\cdot}L^{-1}$, the $NO_3:NH_4$ ratios were adjusted to 100:0, 73:27, 50:50, 27:73, 0:100. Then, root media containing various $NO_3:NH_4$ ratios and equal concentration of other essential nutrients were filled into 50-cell plug trays and the seeds of 'Dotaerang Die' tomato were sown. The investigation of seedling growth and tissue analysis for mineral nutrient contents based on the dry weight of above-ground tissue were conducted 6 weeks after sowing. As seedlings grew, the EC decreased quickly and pH increased gradually in the all treatment media. The plant height, fresh weight and dry weight of seedlings in the treatment of 50:50 ($NO_3:NH_4$) were 29.0 cm, 13.7 g, and 1.21 g, respectively, which were the highest among treatments tested. However, the seedlings in the treatment of 0:100 ($NO_3:NH_4$) had 26.5 cm, 11.2 g, and 0.92 g in plant height, fresh weight and dry weight, respectively. These were the poorest among the treatments tested. The tissue contents of N were 2.77 to 3.22% in all the treatments. The treatment of 27:73 ($NO_3:NH_4$) had the highest contents of Fe, Mn and Zn and that of 0:100 ($NO_3:NH_4$) had the lowest contents of Mg, Na, Cu, Mn and Zn among the treatments tested. The results indicate that $NH_4$ ratio should be lower than 50% in the coir dust+peatmoss+perlite (3.5:3.5:3, v/v/v) medium for seedling growth of tomato and the optimum ratio will be used to draw up guide lines for plug seedling production.

Etiology and Clinical Manifestations of Fever in Infants Younger than 3 Months Old: A Single Institution Study, 2008-2010 (3개월 미만 영아의 발열에 대한 원인 및 임상양상에 대한 단일기관 연구; 2008-2010)

  • Seok, Joon Young;Kang, Ji Eun;Cho, Eun Young;Choi, Eun Hwa;Lee, Hoan Jong
    • Pediatric Infection and Vaccine
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    • v.19 no.3
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    • pp.121-130
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    • 2012
  • Purpose : The purpose of this study is to investigate clinical features and causative organisms in febrile infants younger than three months, to help identification of high risk patients for serious bacterial infection (SBI). Methods : A total of 313 febrile infants younger than three months, who had visited Seoul National University Children's Hospital from January 2008 to December 2010 were included. Clinical features, laboratory findings, causative organisms, and risk factors of SBI were analyzed by retrospective chart review. Causative bacterial or viral pathogens were identified by gram stain and cultures, rapid antigen tests, or the polymerase chain reaction from clinically reliable sources. Results : Among 313 infants, etiologic organisms were identified in 127 cases (40.6%). Among 39 cases of bacterial infections, Escherichia coli (66.7%) and Streptococcus agalactiae (12.8%) were common. Enterovirus (33.7%), respiratory syncytial virus (19.8%), and rhinovirus (18.8%) were frequently detected in 88 cases of viral infection. Patients with SBI (39 cases) showed significantly higher values of the white blood cell count ($14,473{\pm}6,824/mm^3$ vs. $11,254{\pm}5,775/mm^3$, P=0.002) and the C-reactive protein ($6.32{\pm}8.51mg/L$ vs. $1.28{\pm}2.35mg/L$, P<0.001) than those without SBI (274 cases). The clinical risk factors for SBI were the male (OR 3.7, 95% CI 1.5-8.9), the presence of neurologic symptoms (OR 4.8, 95% CI 1.4-16.8), and the absence of family members with respiratory symptoms (OR 3.6, 95% CI 1.2-11.3). Conclusion : This study identified common pathogens and risk factors for SBI in febrile infants younger than three months. These findings may be useful to guide management of febrile young infants.

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