• 제목/요약/키워드: Drug Combinations

검색결과 97건 처리시간 0.022초

Breakthroughs in the Systemic Treatment of HER2-Positive Advanced/Metastatic Gastric Cancer: From Singlet Chemotherapy to Triple Combination

  • Sun Young Rha;Hyun Cheol Chung
    • Journal of Gastric Cancer
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    • 제23권1호
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    • pp.224-249
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    • 2023
  • Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

목장형 유가공장의 미생물 분석 및 저감기술 적용 평가 (Evaluation of Microbial Analysis and Application of Reduction Technology in a Dairy Factory)

  • 김종희;이은선;김부민;함준상;오미화
    • Journal of Dairy Science and Biotechnology
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    • 제41권4호
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    • pp.203-210
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    • 2023
  • Bacterial contamination negatively affects the quality, functionality, and safety of dairy products. Adherent populations of bacteria, referred to as biofilms, grow on the surfaces of dairy processing equipment and are the primary cause of dairy contamination. In addition, microorganisms present in the farm environment and dairy factory can contaminate the Clear-In-Place (CIP) line through raw milk transport pipes; therefore, exhaustive management is required. In dairy manufacturing facilities, biofilm formation is controlled using CIP systems that primarily require sodium hydroxide and nitric acid. However, the leakage or incomplete removal of these potently active compounds can be harmful to humans. In the present study, we compared the eradication of Escherichia coli and other bacteria using commercially available combinations of sodium hypochlorite (NaClO) and citric acid, which are recognized by the Korean Ministry of Food and Drug Safety (MFDS) as food disinfectants. When considered in the CIP system of the field manufacturing process, E. coli was not detected (compared to detection before treatment), and other bacteria were detected at 0-32 culture-forming units (CFU)/cm2. The residual amount of chlorine ions after CIP treatment was similar to that in tap water, and there was no significant difference in the overall components of the fermented dairy products. Therefore, the NaClO/citric acid CIP system can be safely applied in dairy manufacturing processes.

가축의 설사변에서 분리한 대장균과 살모넬라균의 항균물질 감수성과 마우스에서의 치료효과 (Antimicrobial drug susceptibility and treatment efficacy in mice against Escherichia coli and Salmonella spp isolated from feces of diarrheal animals)

  • 김종만;진남섭;김종완;진영화;이희수;권창희;우승룡;이해천;박종명;김재학;이재진
    • 대한수의학회지
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    • 제37권2호
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    • pp.389-403
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    • 1997
  • Survey on MIC of antimicrobial drugs and its treatment efficacy in mice were conducted for the strains of Escherichia coli and Salmonella spp isolated from feces of young domestic animals with diarrhea in 1996. A total of 338 strains of E coli and 61 strains of Salmonella spp were examined for the susceptibility to 20 antibiotics and 7 synthetic antimicrobial drugs. The results indicated that the majority of strains were susceptible to amikacin(93.5%), cefoperazone/sulbactam(93.5%), cefotaxim(93.3%), cefomandole(92.8%), cefoperazone(91.6%) and ciprofloxacin(85.1%), in order. Although gentamicin, ciprofloxacin and norfloxacin showed the relatively low MIC distributions, erythromycin, doxycycline, sulfamethoxazole and oxytetracycline revealed the high MIC distributions to most of isolates. The $MIC_{90}$ of antimicrobials for E coli were > $62.5{\mu}g/ml$ in gentamicin, $2.0{\mu}g/ml$ in ciprofloxacin, $1.0{\mu}g/ml$ in norfloxacin, > $500{\mu}g/ml$ in erythromycin, $125{\mu}g/ml$ in doxycycline, > $1000{\mu}g/ml$ in sulfamethoxazole and > $250{\mu}/ml$ in oxytetracycline. In general, the MIC of E coli isolates was higher than that of Salmonella spp isolates. Although variation in synergism or additivity of antibiotic combinations were demonstrated, ampicillin-gentamicin was the most efficacious combination both against E coli and Salmonella spp with the fluctuation of 7.7-77.5%. In the experiment of treatment efficacy in mice, the highest survival ratio(83.3%) after challenge with pathogenic E coli and Salmonella typhimurium was detected in the group treated with gentamicin.

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Effect of Herbal Extracts Mixtures on Antioxidant System in Chronic Enthanol-treated Rats

  • Kim, Mok-Kyung;Won, Eun-Kyung;Choung, Se-Young
    • Biomolecules & Therapeutics
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    • 제14권4호
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    • pp.226-234
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    • 2006
  • Disturbance of antioxidant system is very common in chronic alcoholics and herbal or natural products with antioxidant activity have been used for its treatment. This study was to investigate the effect of Vitis vinifera extract(V), Schisandra chinensis extract(S), Taraxacum officinale extract(T), Gardenia jasminoides extract(G), Angelica acutiloba extract(A) and Paeonia japonica extract(P), and their combinations on the antioxidant and ethanol oxidation system. Male Sprague-Dawley rats were subjected to Lieber-DeCarli ethanol liquid diet(ED) and were then given different herbal extract mixtures for 6 weeks including VST(V 100+S 150+T 150mg/kg/day), VSG(V 100+S 150+G 150mg/kg/day), VTG(V 100+T 150+G 150mg/kg/day), and VAP(V 100+A 150+P 150mg/kg/day). When the activity of alcohol dehydrogenase(ADH) and acetaldehyde dehydrogenase(ALDH) were compared between ED only group and herbal extracts treatment group, the differences were statistically significant. Phase I and II(glutathione-S-transferase, phenol sulfatransferase) enzyme activities were found to be significantly higher in the VAT treatment group compared to the ED group. Herbal extracts not only repressed the ethanol-induced elevation of malondialdehyde level, but also protected against ethanol-induced decrease in glutathione content, glutathione reductase, glutathione peroxidase, catalase and superoxide dismutase activities. The administration of the herbal extracts was found to be effective in eliminating lipid-peroxides induced by long-term consumption of alcohol by activating various enzyme systems and physiological active compound formation system. After a chronic consumption of alcohol, Angelica Radix protected the liver via activating the ethanol-metabolism enzyme system, and Paeoniae Radix via activating the ethanol-metabolism enzyme and the phase I, II-metabolism enzyme system. Taraxaci Herba was also effective in liver protection via activating the ethanol-metabolism enzyme system and the phase I, II-metabolism enzyme system, Gardeniae Fructus via activating the phase II-metabolism enzyme system and the anti-oxidation system enzyme, and Schisandra Fructus and a grapestone via activating the anti-oxidation system. Our data suggest that these herbal extracts may be useful as a health functional food or new drug candidate for fatty liver and hepatotoxicity induced by chronic alcohol consumption.

즉석 식품에서 니트로사민이 검출되는 요인 분석 (Factors Attributing to the Formation of N-Nitrosamines in Instant Food)

  • 서보경;권훈정
    • 한국식품위생안전성학회지
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    • 제32권2호
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    • pp.114-122
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    • 2017
  • 본 연구에서는 식품을 용기 포장 채로 조리하는 경우 니트로사민의 함량이 증가하는 사례에서 용기 포장에서의 니트로사민이 용출되는지 확인하였다. 조리를 할 수 있는 용기 포장 31종에 대해 각 식품 유형별로 침출용매를 선택하여 단면용출시험을 진행하였다. 용출 시험을 진행한 결과, 용기 포장에서는 NDMA, NDEA, NDBA가 모두 정량 한계 미만으로만 검출되었다. 따라서 용기 포장물질에서 침출용매로의 용출은 미미하였고 침출용매가 아닌 특정 식품에 의한 차이가 있는지 확인하고자 하였다. 토마토소스를 제외한 레토르트 시료는 조리 전과 후의 유의적인 함량 차이가 없었으며 컵라면 시료의 경우는 모든 시료에서 조리 전 NDMA가 불검출되었지만 조리 후 NDMA 함량이 trace${\sim}0.93{\mu}g/kg$로 검출되었다. 컵라면의 NDMA 함량 증가 원인을 파악하기 위해 구성요소인 면, 분말스프, 건더기스프, 물을 면밀히 검토하였다. 그 결과, 면과 분말스프를 조합하여 조리한 경우에만 NDMA가 생성되었으며 폴리스티렌 제품의 경우 모든 구성요소를 함께 조리할 때보다는 NDMA 함량이 적게 검출되었다. 따라서 컵라면 시료는 면과 분말스프 내의 니트로사민 전구체가 NDMA 생성에 기여하는 것으로 추정되며 건더기스프도 NDMA 함량 증가에 기여하는 것으로 보였다. 따라서 각 구성요소 내의 전구체에 대한 검토가 필요하며 조리 중 가열에 따른 반응을 검토하는 후속연구가 필요할 것으로 추정된다.

소세포폐암의 2차요법으로서의 Topotecan의 치료효과 (Clinical Study of Topotecan as Second-Line Treatment in Small Cell Lung Cancer)

  • 김학렬;양세훈;정은택
    • Tuberculosis and Respiratory Diseases
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    • 제52권3호
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    • pp.230-240
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    • 2002
  • 연구배경 : 소세포폐암은 1차 화학요법에 반응율은 높으나 대부분이 1차 화학요법 1년이내에 진행하고 재발하여, 2차 화학요법에 대한 반응율 및 생존율은 매우 불량하다. 최근 들어 camptothecin 유도체로서 topoiso-merase I 억제제인 topotecan이 소세포폐암의 확장 기에서 1차요법으로서 단독사용시에 39%의 반응율과 10개월의 중앙생존기간이 보고되고 있어, 소세포 폐암의 1차화학요법후 진행, 재발시에 2차요법으로 사용하여 반응율, 생존율 및 부작용등을 검토하였다. 대상 및 방법 : 소세포폐암으로 진단받은 후 1차 화학요법 3주기 시 행후 반응이 없었던 9예와 1차 화학요법 6 주기 완료 후 재발한 10 예, 총 19예를 대상으로 topotecan (hycamtin$^{(R)}$, Glaxo-Smith-Kline, USA) 1.5mg/$m^2$을 매 3주 간격으로 첫 1일부터 5일까지 5일간 30분간에 걸쳐 정맥 투여를 총 6주기 실시하여, 3주기와 6주기후에 반응을 측정하였고, 생존율은 Kaplan-Meier법으로 구하였고, 비교군끼리의 생존율 비교는 Log-rank 검정하였다. 결 과 : 전 대상군에서의 반응율은 26.3% (5/19, CR 2, PR 3, SD 3, PD 11) 이었고, 중앙생존기간은 24주였으며, 1차화학요법의 무반응군 (9예)과 반응군(10예)의 반응율은 각각 22.2%(2/9, PR 2, SD 3, PD 4), 30%(3/10, CR 2, PR 1, PD 7)이었고, 중앙생존기간은 각각 17주, 24주였으며, 1차 화학요법 완료 3개월 이내와 3개월 이후에 재발한 refractory군(6 예)과 sensitive군 (4예)의 반응율은 각각 16.6%(1/6, CR 1, PD 5),50%(2/4, CR 1, PR 1, PD 2)이었고, 중앙생존기간은 각각 14주, 39주였고, 제한기(9예)와 확장기 (10예)의 반응율은 각각 44.4% (4/9, CR 2, PR 2, SD 1, PD 4),10.0%(1/10, PR 1, SD 2, PD 7)이었고 중앙생존기간은 각각 36 주로서 대사예가 적어 통계적 유의성에 이르지는 못하였으나 1차요법 반응군, 1차요법후 늦게 재발한 sensitive군, 제한기의 반응율 및 생존율이 비교적 양호하였다. Topotecan의 유의할 만한 독성 부작용은 전 90주기의 화학요법중 빈혈 grade III 1예, 백혈구 감소증 grade III 6 예, IV 4 예, 혈소판 감소증 grade III 1 예, IV 1예 였으며 구토는 grade III 1예였다. 결 론 : 소세포폐암의 2차 화학요법으로서 topotecan 단독요법은 반응율 26.3%, 중앙생존기간은 24주였으며, 1차 화학요법에 반응을 보인군, 1차 화학요법 완료후 늦게 재발한 군, 제한기의 반응율 및 생존율이 양호하였으며, 더 나아가 다른 2차 화학요법과의 임상대조 시험이 있어야겠다.

항 백혈병작용에 관련된 천연물의 자료조사 (Review of Anti-Leukemia Effects from Medicinal Plants)

  • 배현옥;임창경;장선일;한동민;안원근;윤유식;전병훈;김원신;윤용갑
    • 동의생리병리학회지
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    • 제17권3호
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    • pp.605-610
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    • 2003
  • 인삼, 호장근, 상산 등에서 분리한 성분들이 HL60, HL-60, Jurkat, Molt-4에 대한 억제작용이 있는 것으로 조사되었고, 익모초의 Leonunrine, 대청엽의 Indirubin, 천문동의 Aspargus polysaccharideA.B.C.D, 백합의 Colchicnamile, 익모초의 Lenunrine, 산두근, 자초근 추출물이 여러유형의 백혈병 환자에 대한 백혈병 억제효과가 있는 것으로 조사되었으며, mouse의 P388, L1210, L615, L120, S-180 등에 항 백혈병 효과가 있는 것으로는 완화, 로회, 원지, 오수유, 파두, 뇌공등, 석산, 백출, 단삼, 산약, 목단피, 청대, 감초, 당귀에서 분리한 성분들이 있으며 백굴채, 마전자, 가시오가피, 천초 추출물들이 동물실험에서 항암작용이 있는 것으로 조사되었다. 또 천연물에서 분리한 성분이 항백혈병 작용이 있는것으로는 ginsenoside Ro, ginseonoside Rh2, Emodin, Yuanhuacine, Aleemodin, phorbocdiester, Triptolide, Homolycorine, Atractylol, Colchicnamile, Paeonol, 당귀다당체, Aspargus polysaccharideABCD, Indirubin, Leonunrine, Acinosohic acid, Trichosanthin, G2 132, Schizandrin, allicin, Indirubin, cmdiumlactone chuanxiongol, 18A glycyrrhetic acid, Kansuiphorin A, 13 oxyingenol Kansuiphorin B 등이 조사되었고, 추출물이 항 백혈병 작용이 있는 것으로는 원지, 오수유, 백굴채, 대황, 산두근, 마전자, 가시오가피, 천초 등이 조사되었다.