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Predictive and Prognostic Biomarkers for Patients Treated with Anti-EGFR Agents in Lung Cancer: A Systemic Review and Meta-Analysis

  • Wang, Ying;Qu, Xiao;Shen, Hong-Chang;Wang, Kai;Liu, Qi;Du, Jia-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4759-4768
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    • 2015
  • Background: Several studies have investigated predictive and prognostic biomarkers for patients treated with anti-epidermal growth factor receptor (EGFR) agents in lung cancer. However, the conclusion is controversial. Materials and Methods: A meta-analysis was conducted to evaluate the associations of mutant K-ras, PIK3CA and PTEN deficiency with the efficacy of anti-EGFR agents in lung cancer. The primary endpoint was objective response rate (ORR). The secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 61 studies were included in the final meta-analysis. The result showed that K-ras mutation was a good predictor for ORR (RR=0.42, 95%CI, 0.33-0.55, p=0.000) and an effective prognostic marker for OS (HR=1.37, 95%CI, 1.15-1.65, p=0.001) and PFS (HR=1.33, 95%CI, 1.05-1.69, p=0.019). However, PTEN deficiency or PIK3CA mutation did not show any significance predictive value for ORR (PTEN, RR=0.82, 95%CI, 0.56-1.19, p=0.286; PIK3CA, RR=1.08, 95%CI, 0.17-6.66, P=0.938). And PTEN deficiency or expression of PIK3CA did not show significance prognostic value for OS (PTEN, HR=0.88, 95%CI, 0.31-2.46,P=0.805; PIK3CA, HR=0.79, 95%CI: 0.23-2.68, P=0.706). Conclusions: Our meta-analysis showed that K-ras mutation may be an effective predictor in lung cancer patients treated with anti-EGFR agents. Whereas, the predictive and prognostic value of PTEN deficiency and PIK3CA mutation need to be further investigated.

Ginsenoside Composition Changes in Ginseng Extracts by Different Ascorbic Acid Treatments

  • Ko, Sung-Kwon;Cho, Ok-Sun;Bae, Hye-Min;Sohn, Uy-Dong;Im, Byung-Ok;Cho, Soon-Hyun;Yang, Byung-Wook;Chung, Sung-Hyun;Shin, Wang-Soo;Lee, Boo-Yong
    • Food Science and Biotechnology
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    • v.17 no.4
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    • pp.883-887
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    • 2008
  • The purpose of this study was to develop a new preparation process for chemical transformation of ginseng saponin glycosides to prosapogenins. Ginseng and ginseng extracts were processed under several treatment conditions using ascorbic acid solution. Treating with ascorbic acid at pH 2-3 and above $80^{\circ}C$ increased the ginsenoside $Rg_3$ content of samples to over 3% as compared to other pH levels and temperatures. In addition, ginseng and ginseng extracts that were processed under a high ascorbic acid solution treatment condition (pH 2.0, 5 hr) contained more ginsenoside $Rg_3$ (approximately 16 times) than those processed under a low ascorbic acid solution treatment condition (pH 3.0, 5 hr). The highest quantity of ginsenoside $Rg_3$ (3.434%) occurred when a sample of fine ginseng root extract (AG2-9) was processed with the ascorbic acid solution at pH 2.0 for 9 hr. However, there was no change in the amount of ginsenoside $Rg_3$ when fine ginseng root extracts were processed with ascorbic acid solution at pH 2.0 for over 9 hr. In conclusion, the results indicated that ascorbic acid treatment of ginseng extracts can produce a level of ginsenoside $Rg_3$ that is over 90-fold the amount found in commercial red ginseng.

Clinical Pharmacokinetics of Vancomycin in Ovarian Cancer Patients (난소암 환자에서 반코마이신의 임상약물동태)

  • Kim, Yang Woo;Choi, Jun Shik;Lee, Jin Hwan;Park, Jae Young;Choi, Byong Chul;Burm, Jin Pil
    • Korean Journal of Clinical Pharmacy
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    • v.8 no.1
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    • pp.13-18
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    • 1998
  • The purpose of this study was to determine pharmacokinetic parameters of vancomycin using the compartment model dependent and compartment model independent analysis in 6 Korean normal volunteers and 8 ovarian cancer patients. Vancomycin was administered 1.0 g bolus by IV infusion over 60 minutes. The elimination rate constant ($\beta$), volume of distribution (Vd), total body clearance (CLt), and area under the plasma level-time curve (AUC) of vancomycin in normal volunteers using the compartment model dependent analysis were $0.150\pm0.030\;hr^{-1},\;32.9\pm2.81\;L/kg,\;5.36\pm0.63\;L/hr,\;and\;186.5\pm20.5\;{\mu}g/ml{\cdot}hr$, respectively. The $\beta$, Vd, CLt, and AUC of vancomycin in ovarian cancer patients using the compartment model dependent analysis were $0.109\;0.008\;hr^{-1},\;41.5\pm3.01\;L/kg,\;4.58\pm0.57\;L/hr\;and\;218.3\pm22.9\;{\mu}g/ml{\cdot}hr$, respectively. There were significant differences (p<0.05,\;p<0.01) in $\beta$, Vd, CLt, and AUC between normal volunteers and ovarian cancer patients. The elimination rate constant (Kel), CLt, and AUC of vancomycin in normal volunteers using the compartment model independent analysis were $0.152\pm0.022\;hr^{-1},\;5.77\pm0.75\;L/hr,\;and\;173.2\pm22.5;{\mu}g/ml{\cdot}hr$, respectively. The Kel, CLt, and AUC of vancomycin in ovarian cancer patients using the compartment model independent analysis were $0.126\pm0.012\;hr^{-1},\;4.96\pm0.55\;L/hr,\;and\;201.7\pm25.6;{\mu}g/ml{\cdot}hr$, respectively. There were significant differences (p<0.05, p<0.01) in Kel, CLt, and AUC between normal volunteers and ovarian cancer patients. And also, there was significant difference (p<0.05) in Kel of vancomycin in ovarian cancer patients between the compartment model dependent and independen analysis. It is necessary for effective dosage regimen of vancomycin in ovarian cancer patient to use these population parameters.

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Long-term Clinical Outcomes and Prognostic Factors After Endovascular Treatment in Patients With Chronic Limb Threatening Ischemia

  • Jung-Joon Cha;Jong-Youn Kim;Hyoeun Kim;Young-Guk Ko;Donghoon Choi;Jae-Hwan Lee;Chang-Hwan Yoon;In-Ho Chae;Cheol Woong Yu;Seung Whan Lee;Sang-Rok Lee;Seung Hyuk Choi;Yoon Seok Koh;Pil-Ki Min;K-VIS (Korean Vascular Intervention Society) investigators
    • Korean Circulation Journal
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    • v.52 no.6
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    • pp.429-440
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    • 2022
  • Background and Objectives: Endovascular therapy (EVT) first strategy has been widely adopted for the treatment of chronic limb threatening ischemia (CLTI) patients in real-world practice. This study aimed to investigate long-term outcomes of CLTI patients who underwent EVT and identify prognostic factors. Methods: From the retrospective cohorts of a Korean multicenter endovascular therapy registry, 1,036 patients with CLTI (792 men, 68.8 ± 9.5 years) were included. The primary endpoint was amputation-free survival (AFS) defined as the absence of major amputation or death. Secondary endpoints were major adverse limb events (MALE; a composite of major amputation, minor amputation, and reintervention). Results: Five-year AFS and freedom from MALE were 69.8% and 61%, respectively. After multivariate analysis, age (hazard ratio [HR], 1.476; p<0.001), end-stage renal disease (ESRD; HR, 2.340; p<0.001), Rutherford category (RC) 6 (HR, 1.456; p=0.036), and suboptimal EVT (HR, 1.798; p=0.005) were identified as predictors of major amputation or death, whereas smoking (HR, 0.594; p=0.007) was protective. Low body mass index (HR, 1.505; p=0.046), ESRD (HR, 1.648; p=0.001), femoropopliteal lesion (HR, 1.877; p=0.004), RC-6 (HR, 1.471; p=0.008), and suboptimal EVT (HR, 1.847; p=0.001) were predictors of MALE. The highest hazard rates were observed during the first 6 months for both major amputation or death and MALE. After that, the hazard rate decreased and rose again after 3-4 years. Conclusions: In CLTI patients, long-term outcomes of EVT were acceptable. ESRD, RC-6, and suboptimal EVT were common predictors for poor clinical outcomes.

Long-Term Clinical Outcomes of Iliac Artery Endovascular Therapy in the Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases (K-VIS ELLA) Registry

  • Ji Woong Roh;Sanghoon Shin;Young-Guk Ko;Nak-Hoon Son;Chul-Min Ahn;Pil-Ki Min;Jae-Hwan Lee;Chang-Hwan Yoon;Cheol Woong Yu;Seung Whan Lee;Sang-Rok Lee;Seung Hyuk Choi;In-Ho Chae;Donghoon Choi
    • Korean Circulation Journal
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    • v.52 no.7
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    • pp.529-540
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    • 2022
  • Background and Objectives: Limited data are available regarding long-term clinical outcomes of iliac artery endovascular therapy (EVT) in real-world practice. This study investigated long-term outcomes according to Trans-Atlantic Inter-Society Consensus (TASC) classifications. Methods: We analyzed data from 1,705 limbs of 1,364 patients from the retrospective cohort of the multicenter Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease registry. The primary endpoint was target lesion revascularization (TLR)-free survival. Results: TASC A, B, C, and D lesions were present in 19.4%, 26.2%, 28.7%, and 25.7% of the treated limbs, respectively. The technical success rate was 96.2% and did not differ between TASC lesion types. Complications occurred in 6.8% of cases and more occurred in TASC D (11.8%). Iliac artery EVT showed a 5-year TLR-free survival of 89.2%. The TASC D group had the lowest TLR-free rate of 79.3%. TASC D (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.12-2.73; p=0.014), plain old balloon angioplasty (HR, 4.25; 95% CI, 2.03-8.88; p<0.001), current smoker (HR, 1.89; 95% CI, 1.26-2.83; p=0.002), previous bypass surgery (HR, 3.04; 95% CI, 1.28-7.19; p=0.011), combined femoropopliteal treatment (HR, 4.89; 95% CI, 3.19-7.50; p<0.001), combined below the knee treatment (HR, 2.20; 95% CI, 1.25-3.89; p=0.007), and complications (HR, 1.86; 95% CI, 1.07-3.24; p=0.028) were predictors for TLR. Conclusions: Iliac artery EVT achieved excellent technical success and 5-year TLR-free survival. TASC D showed a favorable but lower 5-year TLR-free survival rate and higher complication rate compared with other TASC groups.

Effect of Herbal Extracts Supplementation on Ruminal Methane Production and Fermentation Characteristics In vitro (한약재 추출물 첨가가 in vitro 반추위 발효 시 메탄생성 및 발효성상에 미치는 영향)

  • Lee, Shin-Ja;Lee, Sung-Sill;Moon, Yea-Hwang
    • Journal of Life Science
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    • v.21 no.9
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    • pp.1315-1322
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    • 2011
  • This study was conducted to investigate the effects of several herbal extracts (obtusifolia, cinnamon, chinese pepper, licorice root) on the characteristics of rumen fermentation in vitro. Soybean meal was used as a substrate for fermentation in vitro. Herbal extracts were supplemented to media by 10% of the substrate. The substrates supplemented to Dehority artificial media with herbal extracts were fermented in 30ml serum bottles for 0, 3, 6, 9, 12 and 24 hr at $39^{\circ}C$. Cumulative gas production was significantly (p<0.05) greater in the herbal extract supplements than in the control, in the order of licorice root, chinese pepper, cinnamon and obtusifolia. Methane proportions of the herbal extracts were significantly (p<0.05) higher than that of the control. Licorice root extract supplementation resulted in the lowest methane proportion at 3 hr fermentation. Proportion of hydrogen was significantly (p<0.05) higher in the herbal extract supplements than in the control at 12 hr fermentation. Compared to the control, ammonia concentration in the licorice root was significantly higher at 3 hr fermentation, but lower at 12 hr fermentation (p<0.05). Based on these results, supplementation of the herbal extracts used in this experiment resulted in increased cumulative gas production and stimulating methane production in vitro rumen fermentation.

The Present Situation and Problems of In Vitro Fertilization in Swine (돼지 체외수정의 현황과 문제점)

  • 류일선
    • Journal of Embryo Transfer
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    • v.7 no.1
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    • pp.41-47
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    • 1992
  • 1. In vitro system, LR and FSR accelerated and facilitated meiotic progression, and LH selectively improved cytoplasmic maturation which is required to promote the formation of a male pronucleus. 2. Caffeine (2mM) in the fetilization medium was required not only for inducing zona penetrating ability of boar also for developing to the male pronucleus of the penetrat- ing spermatozoa in vitro. 3. The germinal vesicle (GV)stage was observed for the first 17.6 hr;germinal vesicle break-down (GVBD)stage between 17.6~26.4 hr ;metaphase I (M-I)from 26.4 - 30. 9hr;anaphase I(A-I)ranged from 30. 9~33.4hr;telophase I(T-I) at 33.4~34.4hr; and metaphase II(M-II) at 34.4-48hr. 4. The addition of 10%(v /v) pig follicular fluid (pFF) to maturation media significantly increased the rate of nuclear maturation of pig oocytes (p<0.01), whereas the rate of nuclear maturation of pig oocytes among three different media did not differ. 5. The presence of a primary culture of POEC promotes in vitro development of early cleavage stage pig embryos.

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Changes in Blood Pressure and Heart Rate during Decompressive Craniectomy

  • Jo, Kwang Wook;Jung, Hyun-Ju;Yoo, Do Sung;Park, Hae-Kwan
    • Journal of Korean Neurosurgical Society
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    • v.64 no.6
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    • pp.957-965
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    • 2021
  • Objective : Rapid increase in intracranial pressure (ICP) can result in hypertension, bradycardia and apnea, referred to as the Cushing phenomenon. During decompressive craniectomy (DC), rapid ICP decreases can cause changes in mean atrial blood pressure (mABP) and heart rate (HR), which may be an indicator of intact autoregulation and vasomotor reflex. Methods : A total of 82 patients who underwent DC due to traumatic brain injury (42 cases), hypertensive intracerebral hematoma (19 cases), or major infarction (21 cases) were included in this prospective study. Simultaneous ICP, mABP, and HR changes were monitored in one minute intervals during, prior to and 5-10 minutes following the DC. Results : After DC, the ICP decreased from 38.1±16.3 mmHg to 9.5±14.2 mmHg (p<0.001) and the mABP decreased from 86.4±14.5 mmHg to 72.5±11.4 mmHg (p<0.001). Conversly, overall HR was no significantly changed in HR, which was 100.1±19.7 rate/min prior to DC and 99.7±18.2 rate/min (p=0.848) after DC. Notably when the HR increased after DC, it correlated with a favorable outcome (p<0.001), however mortality was increased (p=0.032) when the HR decreased or remained unchanged. Conclusion : In this study, ICP was decreased in all patients after DC. Changes in HR were an indicator of preserved autoregulation and vasomotor reflex. The clinical outcome was improved in patients with increased HR after DC.

Reduce the Energy Loss in Ruminant; Using Raphanus Sativus Extracts to Mitigate Methane Emission (반추동물의 에너지 손실을 줄이기 위한 연구; 무 추출물을 이용한 메탄 손실 억제)

  • Lee, Shin-Ja;Choi, You-Young;Lee, Su-Kyung;Lee, Il-Dong;Eom, Jun-Sik;Kim, Hyun-Sang;Kim, Do-Hyung;Lee, Sung-Sil
    • Korean Journal of Organic Agriculture
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    • v.25 no.4
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    • pp.917-930
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    • 2017
  • This study was conducted to evaluate Raphanus sativus extracts to methane reduction in rumen. Five different levels of R. sativus extracts were used to investigate the most effective dosing level for the decrease of methane production in the rumen. The rumen fluid was collected from a cannulated one Hanwoo cow ($BW=450{\pm}30kg$) consuming 600 g/kg timothy and 400 g/kg concentrate. On fermentation day, rumen fluid was collected at 2 hr postfeeding R. sativus extracts was dosed to achieve final concentration of 0, 1, 3, 5, 7, and 9% respectively, to fermentation bottles containing the mixture of rumen fluid and McDougall's buffer and 300 mg of timothy was added as a substrate. The fermentation was conducted for 3, 6, 9, 12, 24, 48 and 72 hr incubation time at $39^{\circ}C$ with shaking. In vitro ruminal pH values were measured normal range for ruminal fermentation. Dry matter disappearance was significantly higher (p<0.05) at 3 hr incubation time 1, 3 and 5% doses than that of control. The highest methane reduction was observed in 12 hr incubation time 5, 7 and 9%. The carbon dioxide emission was also significantly (p<0.05) lower than that of control at 12 hr incubation time 5, 7 and 9%. The total volatile fatty acid was no significant difference between control and all doses level at 12 and 24 hr incubation time. At 24 hr incubation time, the result of real-time PCR were indicated that M. archea was significantly lower (p<0.05) at all doses level comparing to that of control. In conclusion, R. sativus extracts were significantly decreased methane emission. R. sativus extracts were significantly lower (p<0.05) than that of control at 12 hr incubation time 5, 7 and 9% and no adversely effect in rumen pH, dry matter disappearance and total VFA.

Effects of Coptidis Rhizoma on the Change of Interleukin-6 and $TNF-{\alpha}$ Level induced by LPS I.C.V. Injection in Mice (황연(黃連)이 Lipopolysaccharide 뇌실 주입으로 유발된 생쥐의 IL-6와 $TNF-{\alpha}$ 변화에 미치는 영향)

  • Sim Eun-Yeong;Yun Jeong-Moon;Lee Tae-Hee
    • Herbal Formula Science
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    • v.12 no.1
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    • pp.209-223
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    • 2004
  • Objective: This study was conducted to investigate the effects of Coptidis Rhizoma on the plasma IL-6 and $TNF-{\alpha}$ level in mice by intracerebroventricular(I.C.V.) injection of Lipopolysaccharide (LPS). Method: 6 mice were assigned to each of the Normal group, the Control group, and the individual Experimental groups. In the Normal group only saline was administered intragastrically, and in the Control group LPS was injected intracerebroventricularly 1 hr after intragastric administration of saline. In the Experimental groups Coptidis Rhizoma(0.5g/kg, 1.0g/kg, 3.0g/kg) was administered intragastrically to mice 1 hr prior to LPS (100ng/mouse) I.C.V. Injection. To measure the plasma IL-6 and $TNF-{\alpha}$ level of mice, their blood samples were collected from retro-orbital venous plexus, immediately centrifuged at $4^{\circ}C$, and plasma was removed and stored frozen at $-83^{\circ}C$ for later determination of plasma IL-6 and $TNF-{\alpha}$. Result: 1. LPS I.C.V. Injection increased plasma IL-6 level significantly in a dose-dependent manner compared with Normal group. (P<0.01) The plasma IL-6 concentration reached a significant maximal level about 1 hr after LPS(100ng/mouse) I.C.V. Injection.(P<0.001) 2. Both the 0.5g/kg(Sample A) and 1.0g/kg(Sample B) groups to which Coptidis Rhizoma was administered intragastrically 1 hr prior to LPS(100ng/mouse) I.C.V. Injection showed insignificant lower plama IL-6 level in 1 hr than Control group(P>0.05), and 3.0g/kg group(Sample C) conversely showed higher plama IL-6 level than Control group. 3. LPS I.C.V. Injection increased plasma $TNF-{\alpha}$ level significantly in a dose-dependent manner compared with Normal group.(P<0.05) The plasma $TNF-{\alpha}$ concentration reached a significant maximal level about 1 hr after LPS(100ng/mouse) I.C.V. Injection.(P<0.001) 4. All Sample groups(0.5g/kg, 1.0g/kg, and 3.0g/kg) to which Coptidis Rhizoma was administered intragastrically with each constituent-dose 1 hr prior to LPS(100ng/mouse) I.C.V. Injection showed significant lower $TNF-{\alpha}$ plama level in 1 hr than Control group.(P<0.001) These data revealed that Coptidis Rhizoma might have anti inflammatory effect by reducing the plasma $TNF-{\alpha}$ level in a dose dependent manner in mice LPS I.C.V. Injection.

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