• Title/Summary/Keyword: Breast cancer

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Effective Antitumor Activity of a Recombinant Vaccinia Virus Expressing Murine Interleukin 4 (인터루킨-4를 발현하는 재조합 백시니아 바이러스에 의한 암성장의 억제)

  • Yoon, Kee-Jung;Jin, Ning-Yi;Kim, Sun-Young
    • The Journal of Korean Society of Virology
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    • v.28 no.1
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    • pp.71-78
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    • 1998
  • Vaccinia virus is the prototype orthopoxvirus that has been used as a vaccine strain for small pox. This virus has been used to express a variety of cellular and viral genes in mammalian cells at high levels. Interleukin-4 (IL-4) has been found to stimulate the proliferation of T cells and enhance the cytolytic activity of cytotoxic T lymphocytes. To test the immunotherapeutic potential of IL-4 delivered in vivo by poxvirus, a recombinant vaccinia virus expressing the murine IL-4 gene (RVVmIL-4) was constructed. A high level of IL-4 production was confirmed by infecting HeLa cells and measuring IL-4 in cell culture supernatant by ELISA. As a tumor model, two cell lines were used; the murine T leukemic line P388 and the murine breast cancer line TS/A. CDF1 mice were intraperitoneally inoculated with $1\;{\times}\;10^5$ cells of P388. Mice were injected at the same site with $5\;{\times}\;10^5\;PFU$ of recombinant vaccinia virus; first, 3 days after the injection of tumor cells and thereafter once every week for 3 weeks. Intraperitoneal injections of RVVmIL-4 significantly prolonged the survival time of mice inoculated with tumor cells. All mice injected with RVVmIL-4 remained alive for 30 days after the postinoculation of tumor cells, while 100% and 70% of the animals injected with saline or wild type vaccinia virus died, respectively. In another tumor model using TS/A, tumor was established by subcutaneously inoculating $2{\times}10^5$ tumor cells to BALB/c mice. After tumor formation was confirmed on day 4 in all mice, $5\;{\times}\;10^6\;PFU$ of RVVmIL-4 was inoculated subcutaneously three times, once every week for 3 weeks. The TS/A tumor was eradicated in two of the nine mice. Seven of the nine mice treated with RVVmIL-4 developed a tumor, but tumor growth was significantly delayed compared to those treated with saline or wild type vaccinia virus. These results indicate that recombinant vaccinia viruses may be used as a convenient tool for delivering immunomodulator genes to a variety of tumors.

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Selective Estrogen Receptor Modulation by Larrea nitida on MCF-7 Cell Proliferation and Immature Rat Uterus

  • Ahn, Hye-Na;Jeong, Si-Yeon;Bae, Gyu-Un;Chang, Minsun;Zhang, Dongwei;Liu, Xiyuan;Pei, Yihua;Chin, Young-Won;Lee, Joongku;Oh, Sei-Ryang;Song, Yun Seon
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.347-354
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    • 2014
  • Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for $hER{\alpha}$ and $hER{\beta}$ with $IC_{50}$ values of $1.20{\times}10^{-7}$ g/ml and $1.00{\times}10^{-7}$ g/ml, respectively. LNE induced $17{\beta}$-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on $hER{\alpha}$ and ${\beta}$ than other fractions. Our results indicate that LNE had higher binding affinities for $hER{\beta}$ than $hER{\alpha}$, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.

Tamoxifen Induces Mitochondrial-dependent Apoptosis via Intracellular Ca2+ Modulation (탐옥시펜에 의해 유도된 세포 내 칼슘농도 변화와 미토콘드리아 의존적 세포사멸)

  • Jang, Eun-Seong;Kim, Ji-Young;Kim, Byeong-Gee
    • Journal of Life Science
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    • v.17 no.8 s.88
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    • pp.1053-1062
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    • 2007
  • In the present work, we show that tamoxifen(Tam)-induced cytotoxicity is due to the mitochondrial-dependent pathway triggered by the intracellular $Ca^{2+}$ increase in MCF-7 human breast cancer cells. Tam induced the intracellular $Ca^{2+}$ increase. According to the experimental results with $Ca^{2+}$ channel blockers, Tam-induced $Ca^{2+}$ uptake seemed to depend on the voltage-sensitive $Ca^{2+}$ channel at the early stage, but at later stages the intracellular $Ca^{2+}$ increases are more likely due partly to the release of stored $Ca^{2+}$ and partly to the capacitative $Ca^{2+}$ or other entry pathways. Tam-induced $Ca^{2+}$ increase led to the release of cytochrome c from mitochondria into the cytosol and the change of mitochondrial membrane potential. In MCF-7 cells, caspase-7 plays a key role in the downstream of apoptosis because caspase-3 is absent. In the cells treated with Tam, caspase-7 cleavage was increased almost two-fold. There was no marked alteration in the level of anti-apoptotic Bcl-2 protein; however, the cells showed increased expression of pro-apoptotic Bax protein more than two-fold in response to Tam. These results imply that the apoptotic signaling pathway activated by Tam is likely to be mediated via the mitochondrial-dependent pathway.

The Effects of Health Fitness and Body Composition in Elderly Men for 16 Weeks of Tai Chi Exercise (16주간의 태극권 운동이 남자 고령자들의 건강체력 및 신체조성에 미치는 영향)

  • Kim, Cheol-Woo
    • Journal of Life Science
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    • v.21 no.8
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    • pp.1127-1133
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    • 2011
  • Exercise has been shown to positively influence quality of life for elderly men with a wide variety of medical illnesses. Tai chi exercise, a slow and graceful form of exercise and meditation, has especially been offered as the ideal exercise for elderly men with diverse conditions, such as people suffering from chronic heart failure or breast cancer survivors. In one recent study, Tai Chi was found to improve exercise capacity, sleep stability, and quality of life in heart failure patients including elderly men. The purpose of the study was to examine the effects of 16 weeks of Tai Chi exercise (3 times/week, 60 min/trial, 40-50% HRR) on physical and physiological changes. Sixty four healthy volunteers without any particular disease between the ages of 65 and 79 years participated in the study. The results were as follows; Significant changes of cardiac endurance, strength, muscle endurance, flexibility and balance were observed following 16 weeks of Tai Chi exercise (p<0.05). In addition, significant changes of diastolic blood pressure, body fat and fat-free mass were observed following 16 weeks of Tai Chi exercise (p<0.05). These findings suggest that a brief period of Tai Chi exercise is beneficial, particularly to elderly men. It is especially beneficial for body composition, and physical fitness factors such as cardiopulmonary endurance, muscle endurance, flexibility, and balance. Further study is needed in this area for specific disease patients.

The Radiation Protection effect of Tabebuia Avellanedae Extract on the Prostate in Male Rats (수컷 쥐 전립선에 대한 타히보 추출물의 방사선 방호효과 연구)

  • Jeon, Chan-hee;Kim, Jang-Oh;Lee, Yoon-Ji;Lee, Ji-Eun;Lee, Chang-Ho;Min, Byung-In
    • Journal of the Korean Society of Radiology
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    • v.14 no.6
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    • pp.755-762
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    • 2020
  • This study is desinged to examine the effects of Taheebo(Tabebuia avellanedae) extract on the prostate of male rats as a natural radiation protection agent. Taheebo extract is well known to inhibit cell growth for the cell lines of breast and prostate cancer. In this study, the X-ray 7 Gy was irradiated in the prostate of male rat to identify radiation protection effects by Taheebo Extracts, 1, 7, and 21 Days later, hematological changes, external toxicity assessments(LDH), antioxidant enzyme(SOD) activity changes and tissue change were observed. IR+TH group showed greater lymphocyte levels than the irradiation group, which is believed to affect the hematopoietic immune system's resilience. As a results of the external toxicity assessment, Taheebo extract's toxicity is maximum 18.128±5.16%, minimum 13.6945±4.43%. Taheebo is considered to be of little toxicity. The composition of prostate cell nuclei and cytoplasm in Control and TH group was honogeneous, whereas the cell nucleus cohesion in the prostate in irradiation group and inflammatory reactions in cytoplasm were shown. IR+TH group showed less inflammatory reactions of cytoplasm in the prostate than in the radiation irradiation group, but showed a cohesive phenomenon of cell nuclei. It is judged that Taheebo extract has radiation protection against prostate cells.

Video-assisted Thoracoscopy in the Treatment of Multi Loculated Pleural Effusion and Empyema (다방성 흉막수 및 노흉 환자에서 비디오 흉강경의 치료)

  • 김영진
    • Journal of Chest Surgery
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    • v.37 no.2
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    • pp.160-165
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    • 2004
  • Successful treatment of multi-loculated pleural effusion or thoracic empyema requires effective drainage and definitive diagnosis of causative organism. The purpose of this study was to assess the efficacy of the video-assisted thoracoscopic surgery in the management of thoracic empyema or multi-loculated pleural effusion after chest tube drainage treatment had failed. Material and Method: Between April 2000 and July 2002, 20 patients with thoracic empyema or multi-loculated pleural effusion that failed to chest tube drainage or other procedures who underwent an operation. All patients were assessed by chest-computed tomogram and underwent video assisted thoracoscopic drainage, debridement, biopsy and irrigation of pleural cavity. Result: In 18 cases (90%), underwent successful video-assisted thoracoscopic surgery. In 2 cases, decortications by mini-thoracotomy were necessary. The ratio of sex was 4 : 1 (16 male: 4 female), mean age was 48.9 years old (range, 17∼72 years), mean duration of postoperative chest tube placement was 8.2 days (range, 4∼22 days), mean postoperative hospital stay was 15.2 days (range, 7∼33 days). Causative disease was tuberculosis, pneumonia, trauma and metastatic breast cancer, There were no major postoperative complications. Symptoms improved in all patients and were discharged with OPD follow up. Conclusion: In an early organizing phase of empyema or multi loculated pleural effusion, video-assisted thoracoscopic drainage and debridement are safe and suitable treatment.

Efficacy of Hormone Replacement Therapy on Lipid Profile and Bone Mineral Density in Postmenopausal Women: Continuous vs. Sequential Treatment (페경기 여성에서 호르몬 대체요법의 지질대사 및 골밀도에 대한 효과: 지속적 요법과 순차적 요법의 비교)

  • Lee, Chang Yun;Lee, Sukhyang
    • Korean Journal of Clinical Pharmacy
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    • v.10 no.3
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    • pp.101-106
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    • 2000
  • Menopausal women experience urogenitory and vasomotor symptoms with increased risk of osteoporosis and cardiovascular diseases, which can be reduced by hormone replacement therapy. However unopposed estrogen therapy has been associated with an increased risk of endometrial hypeiplasia or cancer. The objectives of this study were to compare effects of continuous vs. sequential hormone replacement therapy (HRT) on lipid profile, bone mineral density and menopausal symptoms of postmenopausal women and to assess how they perceive the menopause and HRT culturally. In this retrospective study, women in menopause longer than 6 months, normal in the mam-mogram and Papanicolaou smear, cholesterol level lower than 190 mg/dL or triglyceride level lower 4han 500 mg/dL were treated with Srogen (conjugated equine estrogen 0.625 mg tablet) and Provera (medroxyprogesterone acetate 2.5 mg tablet) for continuous treatment(CT) or Cycloprogynova (Estradiol valerate 2 mg and Norgestrel 0.5 mg complex tablet) for sequential treatment(ST). They were evaluated for lipid profile, bone mineral density, menopausal symptoms, side effects and their perception of menopause and HRT. As results, total sixty-seven patients out of ninety-four enrollees were included in final analysis (33 in continuous therapy, 34 in sequential therapy). There were significant decrease in total cholesterol ($15.04\pm3.17$, p=0.0001), LDL ($19.72\pm3.27$, p=0.0001), and increase in HDL ($5.89\pm1.63$, p=0.0001). Bone minora) density increased significantly with HRT ($0.02\pm0.11$, p=0.0001). But, there were no significant differences in change of lipid profile between continuous and sequential therapy: Total cholesterol, $13.12\pm4.7\;vs.\;16.91\pm4.3;\;LDL\;20.53\pm4.1\;vs.\;18.93\pm5.12:HDL\;7.15\pm2.3\;vs.\;4.67\pm2.2,\;p>0.05$. Incidences of flush reduced from $75\%\;(CT)\;to\;3.13\%\;and\;71.88\%\;(ST)\;to\;9.35\%$. The change of endometrium and breast were found 3 (CT) and 5 (ST) women, respectively. Most of women recognized that HRT is necessary $(70\%)$ for postmenopausal period but did not understand well the cardiovascular protective effect. In conclusion, hormone replacement therapy was effective in improving lipid profile, bone mineral density and menopausal symptoms in both continuous and sequential treatments with similar efficacy.

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Determination of 4 Parabens in Human Urine by Online SPE and LC-MS/MS Techniques (온라인 고체상추출과 LC-MS/MS 기술을 이용한 소변 중 파라벤류 분석)

  • Kim, Jung Hoan;Kho, Young Lim;Kim, Pan Gyi;Jeong, Jee Yeon;Lee, Eun Hee;Lee, Seung-Youl;Nam, Hye-Seon;Rhee, Gyu-Seek
    • Journal of Environmental Health Sciences
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    • v.38 no.6
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    • pp.561-567
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    • 2012
  • Objectives: Parabens are widely used as antimicrobial agents in pharmaceuticals and cosmetics as well as by the food industry. Parabens have been reported to show weak estrogenic activity and be related to health effects such as allergic reactions and skin and breast cancer. We evaluated an online solid phase extraction (SPE) method coupled with LC-MS/MS technique using free and conjugated parent parabens in human urine for assessing human exposure to parabens. Methods: We employed LC/MS/MS through online solid phase extraction and column-switching techniques and analyzed free and conjugated parabens as biomarkers of human exposure. Four major parabens, methyl-paraben (MP), ethyl-paraben (EP), propyl-paraben (PP) and butyl-paraben (BP), were analyzed. Method validation was performed by sensitivity, accuracy, precision and comparison of the results of online SPE with offline SPE. Results: The limits of detection (LOD) were in the range of 0.2-2 ng/mL, and actual limits of quantification (LOQ) were in the range of 0.7-6 ng/mL urine, depending upon the compound. Accuracy was in the range of 98.3-106.4%, and precision was in the range of 1.3-8.7% (CV) depending upon the compound. We found a good correlation between the results of analysis by online SPE method and that by off-line SPE method. Conclusions: The online SPE method showed proper LOD and validated accuracy, precision and good correlation with the offline method for analyzing parabens in urine.

Solid-Phase Refolding of Poly-Lysine fusion Protein of hEGF and Angiogenin (Poly-lysine이 연결된 hEGF와 angiogenin의 융합단백질의 고체상 재접힘)

  • Park, Sang-Joong;Ryu, Kang;Suh, Chang-Woo;Chai, Young-Gyu;Kwon, Oh-Byung;Park, Seung-Kook;Lee, Eun-Kyu
    • KSBB Journal
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    • v.17 no.2
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    • pp.153-157
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    • 2002
  • A fusion protein, consisting of a human epidermal growth factor as the recognition domain and human angiogenin as the toxin domain, can be used as a targeted therapeutic against breast cancer cells among others. The fusion protein was expressed as an inclusion body in recombinant E. coli, yet when the conventional solution-phase refolding process was used the refolding yield was very low due to severe aggregation, probably because of the opposite surface charge resulting from the vastly different pl values of each domain. Accordingly the solid-phase refolding process, which exploits the ionic interactions between a solid matrix and the protein, was tried, however the ionic binding yield was also very low regardless of the resins and pH conditions used. Therefore, to provide a higher affinity toward the solid matrix, six Iysine residues were tagged to the N-terminus of the hEGF domain. When cation exchange resins, such as heparin- or CM-Sepharose, were used as the matrix, the adsorption capacity increased 2.5~3-fold and the subsequent refolding yield increased nearly 15-fold compared to the conventional process. A similat result was also obtained when an Ni-NTA metal affinity resin was used.

Synthesis of I-125 Labelled Compound of Taxol Analogue for Radioimmunoassay (Taxol의 방사면역측정을 위한 I-125 표지화합물 합성)

  • 오옥두;금준섭;이양호;박용석;편웅범;최창운
    • Biomedical Science Letters
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    • v.3 no.2
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    • pp.125-130
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    • 1997
  • Taxol, an anticancer drug that has diterpenoid conformation, has been used as an effective chemotherapeutical agent in the treatment of breast and ovarian cancers. Because of its toxicity like other anticancer drugs, monitoring the taxol level in serum is important procedure during cancer therapy. The various monitoring methods using HPLC, ELISA, and RIA have been adopted, and RIA technique is known to be superior than other methods in trems of sensitivity and convenience. In this study, in order to develope taxol RIA system using $^{125}$I labelled antigen, first of all we synthesized taxol derivatives. 2'-hemisuccinyltaxol was obtained with about 80% yield by esterification of taxol at C-2' hydroxyl group on C-13 carbon with succinic anhydride. [$^{125}$I]iodotyramine was prepared with 58% labelling yield by radioiodination of tyramine and purified by gel chromatography. 2'-[$^{125}$I]iodotyramine-hemisuninyltaxol, $^{125}$I labelled antigen for taxol RIA, was synthesized with 96% yield from conjugation of 2'-hemisuccinyltaxol and [$^{125}$I]iodotyramine. Anti-taxol serum was produced from the rabbit immunized with 2'-hemisuccinyltaxol-BSA synthesized by 2'-hemisuccinyltaxol and BSA. The antiserum titer was determined by RIA using 2'-[$^{125}$I]iodotyramine-hemisuccinyltaxol. The titer of 1:20 was obtained with about 40% of B/T. The results suggest that taxol RIA using $^{125}$I labelled antigen can be applied to monitor the taxol level in serum.

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