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Efficacy of First-Line Targeted Therapy in Real-World Korean Patients with Metastatic Renal Cell Carcinoma: Focus on Sunitinib and Pazopanib

  • Kim, Myung Soo;Chung, Ho Seok;Hwang, Eu Chang;Jung, Seung Il;Kwon, Dong Deuk;Hwang, Jun Eul;Bae, Woo Kyun;Park, Jae Young;Jeong, Chang Wook;Kwak, Cheol;Song, Cheryn;Seo, Seong Il;Byun, Seok-Soo;Hong, Sung-Hoo;Chung, Jinsoo
    • Journal of Korean Medical Science
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    • v.33 no.51
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    • pp.325.1-325.10
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    • 2018
  • Background: To evaluate survival outcomes and prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who received sunitinib (SU) and pazopanib (PZ) as first-line therapy in real-world Korean clinical practice. Methods: Data of 554 patients with mRCC who received SU or PZ at eight institutions between 2012 and 2016 were retrospectively reviewed. Based on the targeted therapy, the patients were divided into SU (n = 293) or PZ (n = 261) groups, and the clinicopathological variables and survival rates of the two groups were compared. A multivariable Cox proportional hazard model was used to determine the prognostic factors for OS. Results: The median follow-up was 16.4 months (interquartile range, 8.3-31.3). Patients in the PZ group were older, and no significant difference was observed in the performance status (PS) between the two groups. In the SU group, the dose reduction rate was higher and the incidence of grade 3 toxicity was more frequent. The objective response rates were comparable between the two groups (SU, 32.1% vs. PZ, 36.4%). OS did not differ significantly between the two groups (SU, 36.5 months vs. PZ, 40.2 months; log-rank, P = 0.955). Body mass index, Eastern Cooperative Oncology Group PS > 2, synchronous metastasis, poor Heng risk criteria, and liver and bone metastases were associated with a shorter OS. Conclusion: Our real-world data of Korean patients with mRCC suggested that SU and PZ had similar efficacies as first-line therapy for mRCC. However, PZ was better tolerated than SU in Korean patients.

Leaching Characteristics of Arsenic and Heavy Metals and Stabilization Effects of Limestone and Steel Refining Slag in a Reducing Environment of Flooded Paddy Soil (담수된 논토양의 환원 환경에서 비소 및 중금속의 용출특성과 석회석 및 제강슬래그의 안정화 효과 검토)

  • Yun, Sung-Wook;Kang, Sin-Il;Jin, Hae-Geun;Kim, Ha-Jin;Yu, Chan
    • Journal of agriculture & life science
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    • v.45 no.6
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    • pp.251-263
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    • 2011
  • In order to investigate treatment effects of limestone and steel refining slag for paddy soils contaminated with arsenic and heavy metals, a lab-column test was carried out under reducing environments of flooded paddy soils. In conditions of the flooded paddy soils, at the point of time when iron and manganese were reduced and leached rapidly, heavy metals also leached rapidly, and some leachate samples from an untreated soil exceeded regulatory standards. On the contrary, all samples from soils treated with limestone 5% and steel refining slag 5% respectively were below the regulatory standards, showing much lower heavy metal concentrations than in the untreated soil. Arsenic increased continuously during the observation period according to its typical characteristics, and along with decreasing redox potential, arsenic was expected to leach as $H_3AsO_3$-of form $A^{3+}$ with high mobility and strong toxicity. Limestone and steel refining slag showed high treatment effects against heavy metals present in soil and steel refining slag especially showed the high treatment effects against arsenic.

Development of Thermo-Cosmetics Using Photothermal Effect of Gold Nanoparticles (금 나노입자의 광열효과를 이용한 온열화장품 개발)

  • Lee, Jae-Yeul;Kim, Bo-Mi;Park, Se-Ho;Choi, Yo-Han;Shim, Kyu-Dong;Moon, Sung-Bae;Jang, Eue-Soon;Yang, Seun-Ah;Jhee, Kwang-Hwan
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.41 no.1
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    • pp.27-34
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    • 2015
  • Many applications of nanoparticles have been developed since 1970s. Surface plasmon resonance (SPR) effect can be generated at the surface of nanoparticles by illumination. SPR is the resonant oscillation of conduction electrons at the surface material stimulated by incident light. The collisions between excited electrons and metal atoms can cause the production of thermal energy (photothermal effect). Here, we presented the development of thermo-cosmetics using photothermal effect of gold nanoparticles. Gold nanoparticles (GNPs) were chosen for it's low toxicity. We also and investigated the cell biocompatibility and heating effectiveness for photothermal effect of GNPs. Synthesized GNPs were verified by UV-vis spectrophotometer, where GNP has a characteristic absorbance spectrum. Concentration of GNP was measured by atomic absorption analyzer. The cytotoxicity was confirmed by MTT assay and double staining assay. Photothermal effect of GNP was demonstrated by the thermal increasing properties depending on GNP concentration, which was taken by an IR-thermal camera with a xenon lamp as the light source. If the thermal effect of GNP is applied for thermo-cosmetics, it can supply heat to skin by converting solar energy into thermal energy. Thus, cosmetics containing GNPs can provide benefits to people in the cold region or winter season for maintaining skin temperature, which lead to a positive effect on skin health.

Synthesis and Biocompatibility Study of Hydrogel for Patch Sensor in Non-invasive Glucose Monitoring System (무채혈 혈당 측정시스템의 Patch Sensor용 수화젤의 합성 및 생체적합성에 관한 연구)

  • Kwon, Jeong-Woo;Kim, Dong-Chul;Yoon, In-Joon;Jeong, Yoon-Na;Jeong, Ji-Young;Hwang, In-Sik
    • Polymer(Korea)
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    • v.33 no.2
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    • pp.111-117
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    • 2009
  • This study aims to verify for humans the suitability of the enzyme-fixed hydrogel used for the patch sensor of the blood sugar testing system without blood sampling, which utilizes reverse iontophoresis. Using acrylate monomers, hydrogel was synthesized to which a certain unit of enzyme is fixed. In order to analyze the material property of the synthesized hydrogel, a structural analysis was performed using FT-IR spectroscopy, while the DSC was used to verify the thermal stability. In addition, with the UV-Vis spectrophotometer, it was verified that the degree of active enzyme is at least 50% greater than the standard product. The SEM was used to verify secure fixation of the enzyme onto the surface. As a result, it was observed that the enzyme is successfully fixed to the surface. Since the hydrogel makes direct contact with a patient's skin, it is essential to evaluate the toxicity when making direct contact with the skin. For that purpose, various sets of tests were undertaken according to the ISO 10993-cytotoxicity, intracutaneous reactivity, skin irritation test and maximization sensitization. Consequently, it was successfully verified that the enzyme-fixed hydrogel have bioavailability.

The Factors that Predict Using Mechanical Ventilation for Patients with Organophosphate Intoxication (유기인계 농약 중독환자에서 기계환기 필요성에 대한 예측인자 분석)

  • Park, Dong-Chan;Park, Jung-Bae;Kim, Yun-Jeong;Shin, Soo-Jeong;Mun, You-Ho;Park, Sin-Ryul;Ryoo, Hyun-Wook;Seo, Kang-Suk;Chung, Jae-Myung
    • Journal of The Korean Society of Clinical Toxicology
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    • v.8 no.2
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    • pp.106-112
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    • 2010
  • Purpose: The purpose of this study is to investigate the factors that predict using mechanical ventilation for patients with organophosphate intoxication. Methods: We retrospectively reviewed the medical records of 111 patients with acute organophosphate intoxication and who were treated in our emergency center from January 2000 to December 2008. We compared the toxicologic characteristics, the laboratory findings and the APACHE II scores between the Mechanical Ventilation group (MV group) and the non-Mechanical Ventilation group (the non MV group). Results: Sixty three patients were in the MV group and 48 patients were in the non MV group. In the MV group, the patients had an older age (p<0.001), a larger amount of ingestion (p<0.001), a lower initial serum cholinesterase level (p=0.003), a higher APACHE II score (p<0.001) and they ingested a more toxic agent (p=0.001). There were no significant differences in gender, the type of visit and the arrival time between the MV group and the non MV group. Conclusion: We suggest that the patient's age, the amount of organophosphate ingestion, the toxicity of the agent, the initial serum cholinesterase level and the APACHE II score are important factors to determine if mechanical ventilation will be applied for patients with organophosphate intoxication.

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Acute Pancreatitis after Carbamate Poisoning (카바메이트 중독 후 발생한 급성췌장염)

  • Park, Joseph;Kim, Yong Won;Oh, Se Hyun;Cha, Yong Sung;Cha, Kyoung Chul;Kim, Oh Hyun;Lee, Kang Hyun;Hwang, Sung Oh;Kim, Hyun
    • Journal of The Korean Society of Clinical Toxicology
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    • v.12 no.2
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    • pp.77-84
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    • 2014
  • Purpose: Carbamate insecticides are potent cholinesterase inhibitors capable of causing severe cholinergic toxicity. Use of carbamate rather than organophosphate insecticides has been increasing. Compared with organophosphate poisoning, relatively few studies have investigated carbamate-associated acute pancreatitis. We investigated general characteristics and pancreatitis of carbamate poisoning and the predictors, among those readily assessed in the emergency department. Methods: We performed a retrospective review of consecutive patients, aged over 18 years, who were admitted between January 2008 and April 2012 to an emergency department (ED) of an academic tertiary care center for treatment of carbamate poisoning. Patients who exhibited poisoning by any other material, except alcohol, were excluded. After application of exclusion criteria, patients were divided according to carbamate-induced pancreatitis and non-pancreatitis groups. Results: A total of 41 patients were included in this study. Among these 41 patients, the prevalence of acute pancreatitis was 36.6% (15 patients). Initial blood chemistry tests showed a statistically higher glucose level in the pancreatitis group, compared with the non-pancreatitis group (222, IQR 189-284 vs. 137, IQR 122-175 mg/dL, P<0.05). Regarding clinical courses and outcomes, a significantly higher proportion of patients developed pneumonia [10 (66.7%) vs. 6 (23.1%), P<0.05] and had a longer hospital stay (7 days, IQR 6-12 vs. 5 days, IQR 2-11, P<0.05), but no difference in mortality, in the pancreatitis group vs. the non-pancreatitis group. In multivariate analysis, the initial glucose was showing significant association with the presentation of carbamate-induced acute pancreatitis (odds ratio 1.018, 95% confidence interval 1.001-1.035, P<0.05). Conclusion: Carbamate-induced acute pancreatitis is common, but not fatal. Initial serum glucose level is associated with acute pancreatitis.

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The Protective Effect of Green Tea Extract on Alpha-amanitin Induced Hepatotoxicity (알파 아마니틴에 의한 간독성에 대한 녹차 추출물의 보호 효과)

  • An, Su Hwan;Sun, Kyung Hoon;Hong, Ran;Lee, Byoung Rai;Park, Yongjin
    • Journal of The Korean Society of Clinical Toxicology
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    • v.17 no.2
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    • pp.58-65
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    • 2019
  • Purpose: Alpha-amanitin induces potent oxidative stress and apoptosis, and may play a significant role in the pathogenesis of hepatotoxicity. This study examined the mechanisms of α-amanitin-induced apoptosis in vitro, and whether green tea extract (GTE) offers protection against hepatic damage caused by α-amanitin (AMA) induced apoptosis in vivo. Methods: The effects of GTE and SIL on the cell viability of cultured murine hepatocytes induced by AMA were evaluated using an MTT assay. Apoptosis was assessed by an analysis of DNA fragmentation and caspase-3. In the in vivo protocol, mice were divided into the following four groups: control group (0.9% saline injection), AMA group (α-amanitin 0.6 mg/kg), AMA+SIL group (α-amanitin and silibinin 50 mg/kg), and AMA+GTE group (α-amanitin and green tea extract 25 mg/kg). After 48 hours of treatment, the hepatic aminotransferase and the extent of hepatonecrosis of each subject was evaluated. Results: In the hepatocytes exposed to AMA and the tested antidotes, the cell viability was significantly lower than the AMA only group. An analysis of DNA fragmentation showed distinctive cleavage of hepatocyte nuclear DNA in the cells exposed to AMA. In addition, the AMA and GTE or SIL groups showed more relief of the cleavage of the nuclear DNA ladder. Similarly, values of caspase-3 in the AMA+GTE and AMA+SIL groups were significantly lower than in the AMA group. The serum AST and ALT levels were significantly higher in the AMA group than in the control and significantly lower in the AMA+GTE group. In addition, AMA+GTE induced a significant decrease in hepatonecrosis compared to the controls when a histologic grading scale was used. Conclusion: GTE is effective against AMA-induced hepatotoxicity with its apoptosis regulatory properties under in vitro and in vivo conditions.

Antioxidant and anti-inflammatory activities of water extracts and ethanol extracts from Portulaca oleracea L. (쇠비름 물, 에탄올 추출물의 항산화 및 항염증 활성)

  • Kim, Dong-Gyu;Shin, Jung-Hye;Kang, Min-Jung
    • Food Science and Preservation
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    • v.25 no.1
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    • pp.98-106
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    • 2018
  • Portulaca oleracea L., a species of Portulacaceae, is ubiquitous. It is a well-known traditional Chinese medicine for removing heat, counteracting toxicity, cooling blood, and maintaining hemostasia; it is also used as antidysentery agent. This study investigated the anti-oxidative and anti-inflammatory activities of water and ethanol extracts from P. oleracea. The total polyphenol content ($21.08{\pm}0.03mg\;GAE/g$) and total flavonoid content ($5.45{\pm}0.76mg\;QE/g$) of the ethanolic extracts were higher than those of the water extracts. The antioxidative activities were determined by evaluating the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging activity and by the ferric reducing antioxidant potential (FRAP) assay. The ABTS radical scavenging activity of the water extract (75.53%) was higher in those of the water extract (67.03%) at concentration of $1,000{\mu}g/mL$. The DPPH radical scavenging activity and FRAP of the ethanol extract were higher than those of the water extract. We also investigated the anti-inflammatory activity of the P. oleracea extracts in LPS-stimulated Raw 264.7 cells. The production levels of nitric oxide (NO) and reactive oxygen species (ROS) significantly decreased with an increasing concentration of the extract. The expression levels of pro-inflammatory cytokines (tumor necrosis faction (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-6) were significantly lower in the ethanol extract than in the LPS alone treatment group. Based on these results, ethanolic extract from P. oleracea could be an effective antioxidant and anti-inflammatory agent.

Protective Effect of water extract Phellinus linteus-discard Schisandra chinensis solid fermented extracts on improvement of sarcopenia by Atorvastatin-induced muscle atrophy cell model (Atorvastatin으로 유도된 근위축 세포모델에서 상황-오미자박 고상발효물 열수추출물의 보호효과)

  • Kim, Young-Suk;Hwang, Su-Jin;Park, Kwang-Il;Lim, Jong-Min;Cheon, Da-Mi;Jung, Yu Jin;Jeon, Byeong Yeob;Kwak, Kyeung Tae;Oh, Tae Woo
    • Herbal Formula Science
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    • v.29 no.4
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    • pp.239-252
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    • 2021
  • Objectives : This study is to effect of improving muscle atrophy through water extract on the solid-phase fermentation extraction with Phellinus linteus of discarded Schisandra chinensis in an atorvastatin-induced atrophy C2C12 cell. Methods : C2C12 myoblast were differentiated into myotube by 2% horse serum medium for 6 days, and then treated solid-phase fermentation(S-P) extract at different concentrations for 24h. To investigate the effect of S-P extract on the induction of muscle atrophy and expression of atrophy-related genes and apoptosis in differentiated C2C12 myotubes using a GSH, ROS, real-time PCR, western blots analysis. Results : As a result of treatment with atorvastatin at concentrations of 5, 10, and 20 uM on the 6th day of differentiation in C2C12 myotube cells, it was confirmed that the cell morphology was damaged in a concentration-dependent manner, and the length and thickness of the myotube also decreased in a concentration-dependent manner. Treatment with S-P extract (50, 100 and 200 ㎍/㎖) increased of GSH and inhibited ROS in the atorvastatin-induced muscle atrophy cell model at a concentration that did not induce toxicity. In addition, it was confirmed that it has an effect on muscle reduction by inhibiting apoptosis of muscle cells as well as being involved in protein production and degradation of muscle cells. Conclusions : Atorvastatin-induced atrophy C2C12 cell, S-P extract activates related to differentiation/generation and proteolysis, and inhibits cell death of atrophy in C2C12 cell. Based on this, it is necessary to prove its effectiveness through animal models and human application test, but it is considered to be discarded Schisandra chinensis can present the potential for development as a recycling industrial material.

Preparation and Characterization of Chitosan-coated PLGA Nanoparticle (키토산이 코팅된 PLGA 나노입자의 제조 및 특성)

  • Yu, Su-Gyeong;Nah, Jae-Woon;Jeong, Gyeong-Won
    • Applied Chemistry for Engineering
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    • v.32 no.5
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    • pp.509-515
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    • 2021
  • In this study, poly lactic-co-glycolic acid (PLGA) nanoparticles (PNP) were prepared through double (w/o/w) emlusion and emulsifying solvent-evaporation technique using PLGA, which has biocompatibility and biodegradability. To maximize stability and bioavailability of the particles, chitosan-coated PLGA nanoparticles (CPNP) were prepared by charge interaction between PNP and chitosan. We demonstrated that CPNP can be utilized as a drug carrier of oral administration. The chemical structure of CPNP was analyzed by 1H-NMR and FT-IR, and all characteristic peaks appeared, confirming that it was successfully prepared. In addition, particle size and zeta potential of CPNP were analyzed using dynamic light scattering (DLS) while morphological images were obtained using transmission electron microscope (TEM). Thermal decomposition behavior of CPNP was observed through thermogravimetric analysis (TGA). In addition, the cytotoxicity of CPNP was confirmed by MTT assay at HEK293 and L929 cell lines, and it was proved that there is no toxicity confirmed by the cell viability of above 70% at all concentrations. These results suggest that the CPNP developed in this study may be used as an oral drug delivery carrier.