• Title/Summary/Keyword: Endothelial test

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Efficacy and Toxicity of Anti-VEGF Agents in Patients with Castration-Resistant Prostate Cancer: a Meta-analysis of Prospective Clinical Studies

  • Qi, Wei-Xiang;Fu, Shen;Zhang, Qing;Guo, Xiao-Mao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8177-8182
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    • 2014
  • Background: Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling pathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumor types, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer (CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patients with CRPC. Materials and Methods: The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to March 31, 2014 were searched for relevant articles. Pooled estimates of the objective response rate (ORR) and prostate-specific antigen (PSA) response rate (decline ${\geq}50%$) were calculated using the Comprehensive Meta-Analysis (version 2.2.064) software. Median weighted progression-free survival (PFS) and overall survival (OS) time for anti-VEGF monotherapy and anti-VEGF-based doublets were compared by two-sided Student's t test. Results: A total of 3,841 patients from 19 prospective studies (4 randomized controlled trials and 15 prospective nonrandomized cohort studies) were included for analysis. The pooled ORR was 12.4% with a higher response rate of 26.4% (95%CI, 13.6-44.9%) for anti-VEGF-based combinations vs. 6.7% (95%CI, 3.5-12.7%) for anti-VEGF alone (p=0.004). Similarly, the pooled PSA response rate was 32.4% with a higher PSA response rate of 52.8% (95%CI: 40.2-65.1%) for anti-VEGF-based combinations vs. 7.3% (95%CI, 3.6-14.2%) for anti-VEGF alone (p<0.001). Median PFS and OS were 6.9 and 22.1 months with weighted median PFS of 5.6 vs. 6.9 months (p<0.001) and weighted median OS of 13.1 vs. 22.1 months (p<0.001) for anti-VEGF monotherapy vs. anti-VEGF-based doublets. Conclusions: With available evidence, this pooled analysis indicates that anti-VEGF monotherapy has a modest effect in patients with CRPC, and clinical benefits gained from anti-VEGF-based doublets appear greater than anti-VEGF monotherapy.

Review of effect on Okchun-hwan for Diabetes Mellitus (당뇨병에 대한 옥천환(玉泉丸)의 효과에 관한 고찰)

  • Kim, Bum Joon;Bae, Go Eun;Choi, Jin Yong;Cho, Jae Hyun;Park, Hye Lim;Hong, Mi Na;Kwon, Jung Nam;Kim, So Yeon;Yun, Young Ju;Lee, In;Choi, Jun Yong;Han, Chang Woo;Hong, Jin Woo;Park, Seong Ha
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.31 no.1
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    • pp.20-24
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    • 2017
  • The aim of this study is to investigate the effect of Okchun-hwan on Diabetes Mellitus. We searched articles from Oasis and Chinese Academic Journals(CAJ) online databases. Searching keywords were '玉泉丸', '옥천환'. Among the articles published from January 2000 to September 2016, The 79 articles were found. After review the title, abstract and original, The five articles were selected finally to rule out a completely different prescriptions and an animal test articles. Okchun-hwan is effective in improving the symptoms(dry mouth and throat, fatigue, eat easy to hunger, shortness of breath, sweating, palpitation, cardiac heat, insomnia, and tongue)of a patient with deficiency of both qi and yin diagnosis(氣陰兩虛證) on Diabetes Mellitus, as well as act on protection of endothelial cells and regulation of insulin sensitivity, insulin resistance that cause the diabetic chronic vascular complications.

Characterization of the Expression of PKCα(Isoform) in DMH-induced Vascular Endothelial Proliferation (DMH에 의한 비정상적인 혈관 내피세포의 증식에서 Protein Kinase C 동종효소 Alpha 단백발현의 특성)

  • Nam, Su Bong;Bae, Yong Chan;Park, Suk Young;Choi, Soo Jong
    • Archives of Plastic Surgery
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    • v.34 no.6
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    • pp.679-684
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    • 2007
  • Purpose: DMH(1,2-dimethylhydrazine) has been known to induce vascular neoplasm such as malignant endothelioma in animal experiment, through induction of abnormal proliferation of HUVECs. In our previous studies, 11 types of PKC isoenzymes were determined by RT-PCR and the expression of $PKC{\alpha}$, and ${\mu}$ was more prominent than other PKC isoenzymes in the DMH-treated group. However, this result was not based on objective assessment. In this study, we further evaluated the role of $PKC{\alpha}$ on the DMH-induced abnormal proliferation of HUVECs by two different methods to identify its presence with high relevance in objective view. $PKC{\mu}$ will be investigated in further study. Methods: The study was conducted with the cultured HUVECs group(control) and the $0.75{\times}10^{-9}M$ DMH-treated group. After processing protein extraction in 0 and 24 hour, extracted protein was treated of quantitative test through BCA protein assay. In the western blot analysis, electrophoresis was performed in the order of gel preparation, sample preparation, and gel running. Electrotransfer to nitrocellulose membrane and reaction with antibody were done. Detection of $PKC{\alpha}$ was achieved through "Gel Image Analysis System". In the fluorescence immunocytochemical analysis, the grading of radiance of the intracellular $PKC{\alpha}$ particles was detected with confocal microscope after treating with primary and fluorescent secondary antibody in 0 and 24 hours. Results: The Western blot analysis showed increased $PKC{\alpha}$ expression from the specimen obtained in 24 hour of the DMH treatment group when compared to those in control group. Under confocal fluorescence microscope, the emitting radiance in the DMH treated group was brighter at 24 hours as well. Conclusion: We believe that $PKC{\alpha}$ plays a role in DMH-induced abnormal proliferation of the vascular endothelium, which may provide insights in understanding the vascular neoplasm.

Screening Test(I) of Several Antipsychotic Agents on NO Formation (수종 정신병치료제들의 NO형성에 대한 검색(I))

  • Lee, Jong-Hwa;EI-fakahany, Esam E.
    • The Korean Journal of Pharmacology
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    • v.30 no.3
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    • pp.343-349
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    • 1994
  • A number of neurological syndromes(e.g. tardive dyskinesia) are developed as a consequence of chronic treatment with neuroleptics or antipsychotic agents. Despite the long and succesful use of phenothiazine derivatives and related agents in the treatment of certain states of mental disease, the mechanisms of these drugs are still poorly understood. One current hypothesis from extensive reviews is that these compounds might significantly interfere with the cyclic nucleotide system in brain (Levin and Weiss, 1977; Nowicki et al., 1991; Haley et al., 1992). Nitric oxide (NO), one of an interesting messenger molecule and aberrant transmitter, is believed to play a important role in biological functions of cyclic nucleotides in nervous system. It has been reported that calcium-dependent NO synthesis in endothelial cytosol is mediated by calmodulin which is supposed to be tightly related to pharmacological actions of antipsychotic agents. In the present study, the effect of several antipsychotic agents on the activity of NO synthesis and formation of cyclic GMP were investigated. These agents inhibited both the formation of $[^3H]L-citrulline$ and that of $[^3H]cyclic$ GMP by concentration-dependent manner, and their inhibiting patterns are so similar to that of calmodulin antagonist.

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Effect of Phyto-Extract Fermented Mixture (MP119) on the Sexual Functions and on the Toxicities of Cadmium (식물추출복합발효물(MP119)이 성기능에 미치는 영향 및 카드뮴 독성에 대한 효과)

  • Jang, Young-Sun;Jeong, Jong-Moon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.12
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    • pp.1724-1731
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    • 2009
  • This study was aimed to investigate the effect of phyto-extract fermented mixture (MP119) on the male sexual functions. The MP119 was evaluated for anti-impotency and anti-hypertensive effects via ACE (angiotensin converting enzyme) or PDE (phosphodiesterase) inhibition assay. $IC_{50}$ values of MP119 against ACE and PDE were 241.3${\pm}$35.5 ppm and 372.2${\pm}$33.8 ppm, respectively. To investigate the effect of testosterone expression by MP119, we performed cell media test using mouse Leydig-derived TM3 cells. Production of testosterone in TM3 cell was increased by MP119. Also, NO (nitric oxide) production of HUVEC (human umbilical vein endothelial cell) was increased when MP119 was added to the cultures. Forty male ICR mice were divided into 4 groups. MP119 was orally intubated for 7 days to group 1 and 3, and same volume of vehicle to group 2 and 4 as controls. After that, group 3 and 4 were intraperitoneally injected cadmium chloride at a single dose of 2 mg/kg. On the 8th experimental day, weights of testis, epididymis and seminal vesicle, number of sperm, concentrations of serum testosterone and cGMP were determined. The number of sperm, the concentrations of testosterone and cGMP were significantly increased in two experimental groups (group 1, 3). These results suggest that MP119 enhanced the sexual function of male mice, and could protect the sexual organs from the cadmium chloride as one of the endocrine disrupters.

Suppression of VCAM-1 Expression in Human Aortic Smooth Muscle Cells Treated with Ethanol Extracts of Cynanchum wilfordii Radix, Arctium lappa L., and Dioscorea opposita (백수오, 우엉, 마 추출물 혼합비율에 따른 혈관부착인자 VCAM-1의 발현억제 효과)

  • Cho, Young-Mi;Song, Hae-Seong;Jang, Seon-A;Park, Dae-Won;Shin, Yu Su;Jeong, Yong Joon;Kang, Se Chan
    • Korean Journal of Plant Resources
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    • v.29 no.5
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    • pp.525-531
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    • 2016
  • Cynanchum wilfordii Radix (CWR), Arctium lappa L (ALL), and Dioscorea opposite (DO) have been known to improve blood lipid profile, blood pressure, and inflammation. To find the optimal combination ratio of CWR, ALL, and DO in terms of vascular health improvement, we compared the effects of various combinations on gene expression of Vascular cell adhesion protein 1 (VCAM-1) in human aortic smooth muscle cells (HASMC). VCAM-1 mediates endothelial leukocyte adhesion and is upregulated in atherosclerosis. Cells was stimulated by TNF-α (10 ng/㎖, 2h) and treated with various combinations for 24 h. A combination (CADM5, CWR:ALL:DO = 2:1:1) showed the strongest suppression of VCAM-1 so that CADM5 was chosen for further experiments. We performed cell viability test with CADM5 (0, 3.125, 12.5, 25, 50, and 100 ㎍/㎖) and no cytotoxicity was found. We also investigated the effect of CADM5 on protein expression of VCAM-1, ICAM-1, Nrf-2, and HO-1 using western blotting. We found that CADM5 diminished the expression of VCAM-1 and increased the expression of Nrf-2 and HO-1. Therefore, we concluded that CADM5 (CWR:ALL:DO = 2:1:1) effectively improves vascular health by regulating the expression of VCAM-1.

Comparison of Different Thawing Methods on Cryopreserved Aorta (냉동 보존된 대동맥의 해동방법)

  • 오영민;심성보;사영조;박재길;곽문섭;이선희
    • Journal of Chest Surgery
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    • v.37 no.2
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    • pp.113-118
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    • 2004
  • The studies on cryopreserved arterial allograft have been focused on cooling methods, pre-treatment, cryoprotectant agents, and preservation temperature. But recently, several studies have reported that thawing methods also play an important role in the occurrence of macroscopic and microscopic cracks. This study was designed to investigate the cell injury after thawing, using a rabbit model to clarify the effect of thawing methods on cryopreserved arteries. Material and Method: Segments of the rabbit aorta were obtained and divided into 3 groups (n=60) according to whether the specimens were fresh (control, n=20), cryopreserved and rapidly thawed (RT) at 37$^{\circ}C$ (n=20), or cryopreserved and subjected to controlled, automated slow thawing (ST)(n=20). Cell damage was established using the TUNEL method and the morphological changes were also evaluated. Result: In the group that was rapidly thawed, the expression of TUNEL (+) cells increased significantly more than in the slowly thawed group. In addition, the endothelial denudation, microvesicles and edema were significant in the rapidly thawed group compared with those changes in the slowly thawed group. Conclusion: Our study suggests that the rapid thawing method may be one of the major causes of cellular damage and delayed rupture in cryopresewed arterial allografts. The expression of TUNEL (+) cells and structural changes were significantly low in the slowly thawed group, which might have contributed to the improvement of graft failure after transplantation.

Wound Healing Effects of Lespedeza cuneata Extract (야관문 추출물의 창상치유 효과)

  • Jung, Hee Kyoung;Kim, Kil-Soo;Jeong, Yoo Seok
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.3
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    • pp.374-380
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    • 2014
  • In this study, the anti-inflammatory effects of Lespedeza cuneata extract on macrophages and wound-healing in wound-induced animal experiments were investigated. In an anti-inflammatory test, 0.1 mg/mL of Lespedeza cuneata extract did not affect growth of RAW 264.7 cells, and Lespedeza cuneata extract suppressed nitric oxide (NO) generation from inflammation-induced macrophages in a concentration-dependent manner. Wounds on the skin of rats were treated with vehicle containing Lespedeza cuneata extract (SSP), vehicle (SCO), and commercial ointment (CCO). The wound and scar sizes in the SSP group were significantly reduced in comparison to the SCO and CCO groups (P<0.05). The epidermis and dermis of the SSP group also recovered faster than the SCO group based on Masson's trichrome staining. The gene expression levels of vascular endothelial growth factor (VEGF) decreased and transforming growth factor-beta 1 (TGF-${\beta}1$) increased in wound tissue from the SSP group compared to that from the SCO group. These results show that Lespedeza cuneata extract accelerates wound-healing through anti-inflammatory activity and induction of collagen regeneration as well as reduces the scar area surrounding wounds. Accordingly, Lespedeza cuneata extract could be useful as a cosmeceutical in the cosmetic industry.

Wound Healing Effects of Rose Placenta in a Mouse Model of Full-Thickness Wounds

  • Kim, Yang Woo;Baek, Seung Ryeol;Lee, Eun Sook;Lee, Sang Ho;Moh, Sang Hyun;Kim, Soo Yun;Moh, Ji Hong;Kondo, Chieko;Cheon, Young Woo
    • Archives of Plastic Surgery
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    • v.42 no.6
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    • pp.686-694
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    • 2015
  • Background Rosa damascena, a type of herb, has been used for wound healing in Eastern folk medicine. The goal of this study was to evaluate the effectiveness of rose placenta from R. damascena in a full-thickness wound model in mice. Methods Sixty six-week-old C57BL/6N mice were used. Full-thickness wounds were made with an 8-mm diameter punch. Two wounds were made on each side of the back, and wounds were assigned randomly to the control and experimental groups. Rose placenta ($250{\mu}g$) was injected in the experimental group, and normal saline was injected in the control group. Wound sizes were measured with digital photography, and specimens were harvested. Immunohistochemical staining was performed to assess the expression of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor-${\beta}1$ (TGF-${\beta}1$), and CD31. Vessel density was measured. Quantitative analysis using an enzyme-linked immunosorbent assay (ELISA) for EGF was performed. All evaluations were performed on postoperative days 0, 2, 4, 7, and 10. Statistical analyses were performed using the paired t-test. Results On days 4, 7, and 10, the wounds treated with rose placenta were significantly smaller. On day 2, VEGF and EGF expression increased in the experimental group. On days 7 and 10, TGF-${\beta}1$ expression decreased in the experimental group. On day 10, vessel density increased in the experimental group. The increase in EGF on day 2 was confirmed with ELISA. Conclusions Rose placenta was found to be associated with improved wound healing in a mouse full-thickness wound model via increased EGF release. Rose placenta may potentially be a novel drug candidate for enhancing wound healing.

Protective Effects of Bojungbangam-tang Extracts on ECV304 Cell Cytotoxicity (보정방암탕 추출물의 혈관내피세포독성에 대한 방어효과)

  • Kwon, Kang-Beom;Kim, Eun-Kyung;Song, Mi-Young;Han, Mi-Jeong;Lee, Su-Yeop;Lee, Heon-Jae;Lee, Young-Rae;Ju, Sung-Min;Ryu, Do-Gon;Kim, Sung-Hoon;Jeon, Byung-Hun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.2
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    • pp.404-407
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    • 2007
  • This study was designed to investigate the protective effect of Bojungbangam-tang Ethanol Extracts (EBJT) on cisplatin and hydrogen peroxide-induced cytotoxicity of human endothelial cell line ECV304 cells. After cells were treated with cisplatin and hydrogen peroxide, MTT assay was performed for cell viability test. To explore the mechanism of cytotoxicity, we used the several measures of apoptosis to determine whether this processes was involved in cisplatin and hydrogen peroxide-induced cell damage in ECV304 cells. Also, cells were treated with EBJT and then, followed by the addition of cisplatin or hydrogen peroxide. Cisplatin or hydrogen peroxide decreased the viability of ECV304 cells in a dose-dependent manner. ECV304 cells treated cisplatin or hydrogen peroxide were revealed as apoptosis characterized by nuclear staining. EBJT protected ECV304 cells from cisplatin or hydrogen peroxide-induced nuclear fragmentation and chromatin condensation. Also, EBJT inhibited the cleavage of poly(ADP-ribose) polymerase (PARP) in cisplatin or hydrogen peroxide-treated ECV304 cells. According to above results, EBJT may protect ECV304 cells from the apotosis induced by cisplatin or hydrogen peroxide.