• 대한한의학회지
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• 제19권2호
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• pp.337-372
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• 1998

To evaluate the effects of Injinchunggantang-derivative on cell viability, cell cycle progression, and apoptosis, MTT assay, cell cycle analysis, Cpp32 protease assay, DNA fragnemtation assay, quantitative RT-PCR, and Western blotting were performed. The results were as followes. In MTT assay, etoposide+Injinchunggantang-derivative-treated cells as well as Injinchunggantang-derivative-treated cells showed higher viability than etoposide-treated cells with no time-concentration-dependence, which implied that Injinchunggantang-derivative has hepato-protective effect Cell cycle analysis showed that Injinchunggantang-derivative has no significant effect on the cell cycle. Cpp32 protease assav and DNA fragmentation assay Injinchunggantang-derivative carry inhibitory effects on apoptosis induction. It was suggested that Injinchunggantang-delivative might regulate the cell cycle, in particular $G_1$ checkpoint by blocking p53 and Watl pathway. Injinchunggantang-derivative inhibited the mRNA expressions of Cpp32, Fas, and Bcl-2, which could result in inhibition of apoptosis. These results imply that Injinchunggantang-derivative increases hepatocyte viability, and protects hepatocyte from damage by regulating the expression of genes associated with cell cycle and apoptosis, which explains the mechanism of the clinical effect of Injinchunggantang-derivative on liver diseases.

• Journal of Gynecologic Oncology
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• 제29권6호
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• pp.89.1-89.8
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• 2018

Objective: Highly effective chemotherapy for patients with low-risk gestational trophoblastic neoplasia (GTN) is associated with almost a 100% cure rate. However, 20%-30% of patients treated with chemotherapy need to change their regimens due to severe adverse events (SAEs) or drug resistance. We examined the treatment outcomes of second-line chemotherapy for patients with low-risk GTN. Methods: Between 1980 and 2015, 281 patients with low-risk GTN were treated. Of these 281 patients, 178 patients were primarily treated with 5-day intramuscular methotrexate (MTX; n=114) or 5-day drip infusion etoposide (ETP; n=64). We examined the remission rates, the drug change rates, and the outcomes of second-line chemotherapy. Results: The primary remission rates and drug resistant rates of 5-day ETP were significantly higher (p<0.001) and significantly lower (p=0.002) than those of 5-day MTX, respectively. Forty-seven patients (26.4%) required a change in their chemotherapy regimen due to the SAEs (n=16) and drug resistance (n=31), respectively. Of these 47 patients failed the first-line regimen, 39 patients (39/47, 82.9%) were re-treated with single-agent chemotherapy, and 35 patients (35/39, 89.7%) achieved remission. Four patients failed second-line, single-agent chemotherapy and eight patients (17.0%) who failed first-line regimens were treated with combined or multi-agent chemotherapy and achieved remission. Conclusions: Patients with low-risk GTN were usually treated with single-agent chemotherapy, while 20%-30% patients had to change their chemotherapy regimen due to SAEs or drug resistance. The second-line regimens of single-agent chemotherapy were effective; however, there were several patients who needed multiple agents and combined chemotherapy to achieve remission.

• Journal of Gastric Cancer
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• 제20권4호
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• pp.395-407
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• 2020

Purpose: A phase II study was conducted to evaluate the safety and efficacy of preoperative, intra-arterial perfusion of epirubicin, etoposide, and oxaliplatin combined with oral chemotherapy S-1 (SEEOX) for the treatment of type 4 gastric cancer. Materials and Methods: A single-center, single-arm phase II trial was conducted on 36 patients with histologically proven type 4 gastric cancer without distant peritoneal or organ metastasis. Patients received 3, 21-day courses of SEEOX preoperative chemotherapy. The primary endpoint was overall survival (OS) and the secondary outcomes assessed were chemotherapeutic response, radical resection rate, pathological regression, toxicities, postoperative morbidity, and mortality. Results: All patients were at an advanced stage of cancer (stage III or IV) and completed the entire course of treatment. Based on changes in tumor volume and peritoneal metastasis, the objective response rate was 55.6% (20/36; 95% confidence interval [CI], 38.5%-72.6%) and the disease control rate was 69.4% (25/36; 95% CI, 53.6%-85.3%). The radical resection rate was 75% (27/36; 95% CI, 60.1%-89.9%) and the proportion of R0 resections was 66.7% (21/36; 95% CI, 50.5%-82.8%). The pathological response rate was 33.3%, of which 13.9% showed complete pathological regression. The median survival was 27.1 months (95% CI, 22.24-31.97 months), and the 2-year OS was 48.5% (95% CI, 30.86%-66.1%). Conclusions: Preoperative SEEOX is a safe and effective treatment for type 4 gastric cancer. Based on these preliminary data, a phase III study will be conducted to confirm the superiority of this regimen over standard treatment.

• Clinical and Experimental Pediatrics
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• 제50권6호
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• pp.524-530
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• 2007

The recent advances in the basic hematology and immunology have significantly enhanced the understanding of histiocytic disorders. The Histiocyte Society which was established in 1985 enabled the randomized trials for these diseases, and important knowledge regarding pathogenesis, clinical presentation, diagnosis, therapy and late consequences has been obtained. The treatment of Langerhans cell histiocytosis (LCH) has varied greatly over last decades, and is still controversial. Therapy can be reduced for low risk patients, and it is possible to discriminate early the non-responding patients with risk disease who might require more intensified treatment. Current therapy of LCH recommended by the Histiocyte Society (LCH-III protocol) is activated in 2001. Hemophaocytic histiocytosis (HLH) is fatal if diagnosis is delayed and appropriate therapy is not instituted rapidly. The diagnostic criteria for HLH is revised by the Histiocyte Society for the current treatment protocol (HLH-2004) which consists of dexamethasone, etoposide, and cyclosporin in combination with intathecal methotrexate. Hematopoietic stem cell transplantation is usually necessary for the primary HLH and recurrent secondary HLH.

• Biomolecules & Therapeutics
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• 제5권3호
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• pp.265-271
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• 1997

Since the advent of chemotherapy, certain types of cancer have been particularly resistant to chemotherapeutic treatment. One of the most well-studied types of resistance is resistance to multiple struc-turally dissimialr hydrophobic chemotherapeutic agents, or multidrug resistance (MDR). We found that MDR cells (KBV20C, KB7D) being highly resistant to colchicine, etoposide, and vincristine were found to have very low level of putrescine and low level of spermidine than the drug sensitive parental cells (KB) but they had almost same level of spermine as the drug sensitive cells. Although both MDR and drug sensitive cells had almost same rate of polyamine uptake, MDR cells were much more sensitive to an inhibitor of polyamine synthesis, methylglyoxal-bis guanylhydrazone (MGBG), suggesting that MDR cells might be defective in polyamine synthesis. These results also suggest that HGBG can be used for treatment of MDR in vivo.

• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2004년도 제4회 발생공학 국제심포지움 및 학술대회
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• pp.73-73
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• 2004

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.71.1-71.1
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• 2003

We show that Cdc6, an essential initiation factor for DNA replication, undergoes caspase-3-mediated cleavage in the early stages of apoptosis in HeLa cells and SK-HEP-1 cells induced by etoposide, paclitaxel, ginsenoside Rh2, or TRAIL. The cleavage occurs at the SEVD$\^$442//G motif and generates an N-terminal truncated Cdc6 fragment (p49-tCdc6) that lacks the carboxy-terminal nuclear export sequence (NES). Cdc6 is known to be phosphorylated by cyclin A-Cyclin A-dependent kinase 2 (Cdk2), an event that promotes its exit from the nucleus and probably blocks it from initiating inappropriate DNA replication. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.149.1-149.1
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• 2003

We have previously shown that 2,4,3',5'-tetramethoxystilbene (TMS), a synthetic trans-stilbene analogue, is one of the most potently selective inhibitor of human cytochrome P450 1B1 in vitro and in vivo. In the present studies, the apoptotic effects of TMS were investigated in HL-60 cells. The effects of TMS on the proliferation of HL-60 cells were determined with MTT assay. TMS exhibited cytotoxicity with an $IC_50$ value of 37 nM. Cotreatment with TMS and etoposide, a well-known anticancer drug significantly enhanced the cytotoxicity. (omitted)

• Radiation Oncology Journal
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• 제17권1호
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• pp.9-15
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• 1999

목적 : 국한성 병기의 소세포 폐암에 대하여 항암 화학 및 흉부 방사선치료의 병합요법을 적용하여 국소 반응율, 급성 부작용의 빈도, 단기 임상 추적 관찰 결과 등을 보고하고자 한다. 대상 및 방법 : 1994년 10월부터 1998년 4월까지 국한성 병기의 소세포 폐암으로 진단되어 VIP 요법(etoposide, ifosfamide, cis-platin) 또는 EP 요법(etoposide, cis-platin)의 복합 항암 화학 및 흉부 방사선치료의 동시 병합요법을 시행받은46명의 환자를 대상으로 하였다. 항암 화학요법은 3주 간격으로 모두 6회의 시행을 목표로 하였고, 흉부 방사선치료는 10MV X-ray를 사용하여 일일선량 2Gy씩 44Gy를 4.5주간에 첫번째 화학요법과 동시에 시행하고자 하였다. 관해율은 예정된 치료가 모두 종료된지 4주만에 판정하였으며, 완전 관해를 얻었던 경우에는 10회에 걸쳐 25Gy의 예방적 전뇌 방사선치료를 예정하였다. 급성 부작용의 빈도와 정도는 SWOG 부작용 판정 등급체계를 적용하였으며, 단기 추적 관찰 결과로서 1년 및 2년 생존율, 무병 생존율 등은 Kaplan-Meter법을 사용하였다. 결과 : 전체 환자에 대한 추적 기간의 중앙값은 16개월이었다(범위 2개월$\~$41개월). 완전 관해는 30명(65$\%$)에서 있었으며, 이 중 22명에서 예방적 전뇌 방사선치료를 시행하였다. 동시 병합요법의 3도 이상의 혈액학적 부작용의 빈도는 각각 백혈구감소증 23명(50$\%$), 적혈구감소증 17명(37$\%$), 혈소판감소증 9명(20$\%$)이었고, 비혈액학적 부작용은 탈모 9명(20$\%$), 오심 및 구토 5명(11$\%$), 그리고 말초신경염 1명(2$\%$)이었으며, 이로 인한 화학요법의 지연은 한명에서, 화학요법제의 용량 감소는 전체 246회의 화학요법 중 58회에서 있었다. 3도 이상의 방사선 식도염은 없었으나 화학요법의 부작용으로 인한 흉부 방사선치료의 일시 중단은 21명에서 평균 8.3일간 필요하였다. 국소 재발은 완전 관해 환자에서 8명, 국소 진행은 부분관해 및 불변 환자에서 6명이 확인되었고, 원격 전이는 17명에서 확인되었으며, 이 중 4명에서 국소 재발과 원격 전이가 함께 확인되었다. 원격 전이의 주요 장기로는 뇌가 10명으로 가장 많았고, 간이 4명으로 다음을 차지하였다. 전체 환자들의 생존기간의 중앙값은 23개월이었으며, 1년, 2년 생존율 및 무재발 생존율은 각각 79%$\%$ 45$\%$ 및 55$\%$, 32$\%$였다. 결론 : 국한성 소세포 폐암환자에서 항암 화학 및 방사선치료의 병합요법을 적용하여 만족할 만한 관해율 및 1년, 2년 생존율을 얻었으며, 대체적인 환자들의 치료 방침에 대한 순응도는 양호한 편으로 판단된다.

• Clinical and Experimental Pediatrics
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• 제51권3호
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• pp.307-314
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• 2008

목 적 : 한국인 음식에 널리 이용되고 있는 중요한 향신료인 고추에 많이 들어있는 capsaicin이 최근 많은 연구를 통해 암을 예방하고 더 나아가 치료할 수 있는 성분으로 밝혀지고 있다. 따라서 본 연구의 목적은 한국인이 많이 섭취하고 있는 식이성분인 capsaicin이 한국인에 많은 위암세포의 세포자멸사의 유도물질로 가능성을 알아보고 이를 항암치료의 일부분으로 시도하고자 하였다. 방 법 : 한국인의 위암세포주인 SNU-668 세포에 capsaicn를 처리한 후 세포 생존은 trypan blue 와 crystal violet 분석, 세포독성은 MTT 분석, 세포사 분석은 핵 응축과 DNA 분절화 실험, bcl-2와 bax의 mRNA 발현은 역전사 중합효소 연쇄반응, 세포사와 관련된 단백질 발현은 Western immunoblot analysis로 분석하였다. Capsaicin에 의해 항암제의 감수성이 증가되는 지를 알아보기 위하여 일정 농도의 capsaicin과 농도 별 각 항암제를 같이 처리하여 2일 간 배양 하고 MTT assay로 분석하였으며 이와 관련된 세포사와 관련된 단백질 발현을 분석하였다. 결 과 : capsaicin의 농도에 따라 SNU-668 위암세포의 증식을 현저히 억제하였으며, 이러한 capsaicin의 증식 억제는 DNA 단편화, 핵 응축과 caspase 활성화에 의해 세포자멸사의 유도에 의한 것으로 입증되었다. 더욱이 capsaicin에 의해 pro-apoptotic Bax에 대한 anti-apoptotic Bcl-2의 비율이 현저히 감소하고, caspase-3활성이 증가하였다. Capsaicin을 처리한 세포는 처리하지 않은 세포에 비하여 etoposide나 adriamycin에 의해 유도되는 세포사멸에 더욱 감수성을 보였다. 결 론 : 이상의 연구에서 capsaicin은 caspase-3 의존적 경로를 통하여 SNU-668 세포에서 세포자멸사를 유도하며 항암제의 감수성을 증가시키므로 위암의 효과적인 항암치료제와 항암제 민감성 유도제의 일환으로 가능성이 있다.