• Journal of Oral Medicine and Pain
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• 제30권2호
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• pp.231-238
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• 2005

항암제의 연구는 화학물질에 민감한 암세포를 죽음에 이르게 하는 세포자멸사와 같은 다양한 세포기능에 초점을 맞추어 왔다. 그러나 약물이 유도한 세포의 죽음에 있어서 핵심적인 분자적 기작은 아직 잘 이해되지 않고 있다. Etoposide는 폐암과 고환암에 사용되는 항암제로서, 본 연구는 etoposide가 사람구강편평상피암종세포(OSC9)에도 세포독성효과와 세포자멸사를 일으키는지를 알아보기 위해 실행하였다. 이 실험에서 etoposide는 농도와 시간 의존적으로 OSC9 세포의 생존율를 현저하게 저해시켰다. TUNEL 염색과 Hoechst 염색을 이용한 핵의 형태학적 관찰에서는 etoposide에 의해 핵이 응축되고 분절되었다. p53의 발현은 48 시간에 증가했으며, etoposide 처리로 인해 caspase-3의 활성을 관찰할 수 있었으며, 그 기질에 해당되는 PARP 단백질은 116-kDa과 89-kDa으로 분절되었다. 위의 결과들은 OSC9 세포에서 etoposide가 유도한 세포자멸사는 caspase-3의 활성과 관련됨을 설명하고 있다.

• Journal of Pharmaceutical Investigation
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• 제38권5호
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• pp.313-317
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• 2008

This study investigated the effect of naringin, a flavonoid, on the bioavailability of etoposide administered orally to rats. Etoposide (6 mg/kg) was administered orally to rats alone or with naringin (1, 4 or 12 mg/kg). Compared with the control group, the co-administration of etoposide with 4 and 12 mg/kg of naringin significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) and the peak plasma concentration ($C_{max}$) of the oral etoposide. Consequently, the absolute bioavailability (AB) of etoposide in the presence (4 and 12 mg/kg) of naringin was significantly (p<0.05) increased by $9.4{\sim}10.6%$ compared with the control group (7.4%). The relative bioavailability (RB) of etoposide was increased 1.13- to 1.44-fold compared to the control group. Enhanced bioavailability of etoposide might be due to inhibition of both cytochrome P450 (CYP) 3A4 in the intestine or liver and P-glycoprotein (P-gp) transport efflux of etoposide in the intestinal membrane. This data indicate that careful consideration of the dosage for therapy with etoposide is required in a case of clinical application of the co-administration of etoposide and naringin.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3973-3976
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• 2012

Background: The aim of this study was to evaluate the efficacy and toxicity of long-term, low-dose oral etoposide as an advanced treatment option in patients with platinum resistant epithelial ovarian cancer. Materials and Methods: For the purposes of this study, 51 patients with histologically-confirmed, recurrent or metastatic platinum-resistant epithelial ovarian cancer (EOC) treated at six different centers between January 2006 and January 2011 were retrospectively evaluated. Patients were treated with oral etoposide (50 mg/day for a cycle of 14 days, repeated every 21 days). Results: Among the 51 platinum-resistant patients, 17.6% demonstrated a partial response and 25.5% a stable response. The median progression-free survival (PFS) was 3.9 months (95% CI, 2.1-5.7), while the median overall survival was 16.4 months (11.8.20.9). No significant relationship was observed between the pre-treatment CA 125 levels, post-treatment CA-125 levels and the treatment response rates (p=0.21). Among the 51 patients who were evaluated in terms of toxicity, grade 1 or 4 hematologic toxicity was observed in 19 (37.3%); and grade 1-4 gastrointestinal toxicity occurred in 15 patients (29.4%). Conclusions: Chronic low-dose oral etoposide treatment is generally effective and well-tolerated in platinum-resistant ovarian cancer patients.

• International Journal of Oral Biology
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• 제33권1호
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• pp.25-31
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• 2008

Inhibition of proteasome activity may reduce many types of cancer, so it's pathway is effective in cancer as well as in clinical fields. Here the author has carried out experiment targeting on the elevation of apoptosis in oral cancer cells by combination of proteasome inhibitor, lactacystin, and DNA replication inhibitor, etoposide. The growth of KB cells was measured by MTT methods and apoptosis was analyzed by DNA fragmentation and Hochest nucleus staining. The proteasome activity was analyzed by fluorescent tagged peptide and cellular protein expression was detected by Western hybridization. Though lactacystin and etoposide inhibited KB cell growth alone, but low combined doses inhibited cell growth more strongly and induced apoptosis. The proteasome activity was also seriously inhibited by the combination of both chemicals. Tumor suppressor proteins and apoptosis inducing proteins were highly increased under the combination of both chemicals. From above studies we can conclude that proteasome inhibitors may be used for the treatment of oral cancer and proteasome inhibitors with DNA replication inhibitors may be effective in clinical trials of oral cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8843-8846
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• 2014

Background: Malignant mesothelioma (MM) is almost always fatal and few treatment options are available. The aim of this study was to evaluate the efficacy of oral cyclophosphamide and etoposide for patients who underwent standard treatment for advanced MM. Materials and Methods: This study included 22 malignant pleural mesothelioma patients who were treated with oral cyclophosphamide and etoposide (EE). Results: The average follow-up period of the patients was 39.1 months. Under the treatment of oral EE, median progression-free survival was 7.7 months [95%CI HR (4.3-11.1)] and median overall survival was 28.1 months [95%CI HR (5.8-50.3)]. The treatment response rates were as follows: 4 patients (27.3%) had a partial response (PR), 12 (54.5%) had stable disease (SD), and progressive disease (PD) was observed in 6 (35.9%). Conclusions: Oral EE can be administered effectively to patients with inoperable malignant mesothelioma who had previously received standard treatments.

• 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.

• 한국식품영양과학회:학술대회논문집
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• 한국식품영양과학회 2001년도 International Symposium on Food,Nutrition and Health for 21st Century
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• pp.69-73
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• 2001

Two opioid peptides, YPLDL and YPLDLF, were isolated from enzymatic digests of spinach ribulose-1, 5-bisphosphate carboxylase/oxygenase (RuBisCO) and named rubiscolin-5 and -6, respectively. These peptides were selective for delta-receptor and the latter was about 3 times more potent than the former. After oral administration in mice at the dose of 100 mg/kg, rubiscolin-6 showed analgesic activity in tail pinch test. It also stimutated learning performance at the same dose in passive avoidance experiment using step-through apparatus. An immunostimulating peptide, MITLAIPVNKPGR, was isolated from a trypsin digest of soybean protein and named soymetide. Immunostimulating activy of soymetide was mediated by fMLP receptor. Interestingly, after oral administration in rats at a dose of 300 mg/kg (po.), soymetide-4 (MITL) protected alopecia (hair-loss) induced by etoposide, a cancer chemotherapy agent. Stimulation of IL-1 release by the peptide was involved in the mechanism. Ovokinin(2-7), RADHPF, is a vasorelaxing peptide released from ovalbumin by the action of chymotrypsin. It lowered blood pressure of spontaneously hypersensive rats (SHR) after oral administration at a dose of 10 mg/kg. RPLKPW, which was designed by replacing 4 amino acid residues in ovokinin(2-7), exhibited hypotensive activity at a dose of 0.1 mg/kg (po.). This peptides was introduced into 3 homologous sites in soybean beta-conglycinin alpha' subunit by site-directed mutagenesis of the cDNA and expressed in E. coli. The minimum effective dose for hypotensive activity of the genetically modified beta-conglycinin alpha' subunit was 10 mg/kg (po.), which is about 1/200 that of ovalbumin.

• Journal of Digestive Cancer Research
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• 제3권1호
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• pp.30-34
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• 2015

전이성 위암에서 1차 항암화학요법은 생존 기간을 연장시키고 삶의 질을 향상시키므로 환자의 전신 상태가 양호하다면 표준 요법으로 시행되어야 하며, 국내에서는 fluoropyrimidine과 platinum의 병합 요법이 가장 흔하게 사용된다. 또한 1차 치료에 실패한 위암 환자에서 2차 항암화학요법은 표준 치료이며, 환자의 전신 상태에 따라 그 시행을 적극적으로 고려해야 한다. HER2 양성 위암에서는 trastuzumab 포함 복합 항암화학요법을 시행해야 하며, 진행성 위암으로 진단 시 먼저 HER2/neu 과발현 여부를 확인하는 것이 매우 중요하다. 최근 혈관 신생 성장인자와 관련된 ramucirumab의 항암효과에 대한 임상 결과가 보고되었고, 현재 진행성 위암 환자를 대상으로 C-MET, PI3K, FGFR 및 immune checkpoint 등과 연관된 여러 새로운 표적 치료제에 대한 임상 연구가 활발히 진행되고 있으므로 이들 연구 결과가 임상 현장에 적용될 경우 향후 환자들의 생존과 삶의 질을 향상시키며, 더 나아가 환자 개개인의 분자적, 유전적 특성에 맞는 치료를 할 수 있을 것으로 전망되는 바이다. 저자들은 전신 상태가 비교적 양호하고 고령이 아닌 55세의 남자 환자가 T3N3M0 (Stage IIA)의 진행성 위암을 진단받고 수술적 치료 후 추적 관찰 도중에 간에 다발성의 전이성 병변들이 새롭게 확인되어 고식적인 항암화학요법의 실제 임상에서의 적용을 보고하고자 본 증례를 문헌 고찰과 함께 보고하는 바이다.

• Radiation Oncology Journal
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• 제17권2호
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• pp.100-107
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• 1999

목적: N2 병기 비소세포폐암에서 수술 전 동시화학방사선요법과 수술을 적용하여 급성 부작용, 수술 절제가능성 및 수술 후 병기 강하율을 보고하고자 한다. 대상 및 방법: 1997년 5월부터 1998년 6월까지 삼성서울병원에서 N2 병기 비소세포폐암으로 진단 받은 15명의 환자들을 대상으로 하였다. 환자들 연령의 중앙값은 61세(45~67세), 남녀 성비는 12:3 이었으며 세포 조직형은 편평상피암종이 11명, 선암종이 4명이었다. 치료 전 임상적 T병기는 T1, T2, 및 T3가 각각 2명, 12명, 및 1명씩이었으며 모든 환자들이 N2 병기로서 이중 10명은 종격동내시경을 통한 조직생검을 통하여 종격동 림프절 전이를 확인하였고 나머지 5명은 흉부 CT 영상 상 종격동 림프절 전이가 강력히 의심된 경우였다. 수술 전 방사선치료는 흉부 CT영상을 기준으로 하여 원발 병소, 동측 폐문부 및 종격동 림프절에 대하여 10MV X-선을 이용하여 45Gy를 5주간에 걸쳐서 조사하도록 계획하였다(일회 선량 1.8 Gy, 일일 1회, 주 5회). 수술 전 복합화학요법은 cis-Platin(100mg/m$^{2}$)을 제 1일에 급속 정주하고 Etoposide(50mg/m$^{2}$/day)를 제 1일부터 제 14일까지 경구로 2회에 분복하도록 하였으며, 첫번째 화학요법은 방사선치료의 시작일에, 두 번째 화학요법은 4주 후에 시행하도록 계획하였다. 수술은 방사선-복합화학요법의 완료 3주째에 흉부 CT 영상을 얻어 병변의 진행이나 원격전이의 소견이 없음을 확인한 후 시행하였다. 결과 : 방사선치료는 15명 모두에서 계획된 목표 선량 45Gy를 조사하였으며, 복합 화학요법은 11명의 환자에서는 계획대로 2회를, 나머지 4명에서는 1회만 시행하였다. 본 연구의 치료 방법과 관련하여 1명의 환자가 수술 15일만에 급성 호흡부전으로 사망하였으며 입원치료를 요하는 정도의 급성 부작용의 발현은 방사선폐렴과 호중구 감소로 인한 발열이 각각 1명, 2명이었다. 급성 식도염은 RTOG grade 1이 9명, grade 2가 3명으로 대체로 경미한 편이었다. 총 26회의 복합 화학요법과 관련된 급성 부작용으로 grade 3 이상의 백혈구 감소증, 혈소판 감소증, 및 빈혈이 각각 26.9%, 7.7%, 3.8%에서 나타났다. 수술을 시행한 환자는 13명으로 이 중 12명에서 근치적 절제술이 가능하여 수술절제율은 92.3%(12/13) 이었다. 한 명에서는 수술 시 늑막 전이가 확인되어 절제 수술을 시행하지 못하였다. 다른 2명은 수술을 거부하였다. 수술 후 병리학적 T병기는 T0, T1, 및 T2가 각각 3명, 6명, 및 3명이었으며 N병기는 N0, N1, 및 N2가 각각 8명, 1명, 및 3명이었다. 병리학적 완전 관해는 모두 3명의 환자에서(27.3%) 확인되었으며, 수술 전 임상적 병기와 비교하여 볼 때 병기 강하, 불변, 상승이 각각 8명(61.5%), 4명(30.8%), 1명(7.7%) 이었다. 결론 : N2 병기 비소세포폐암에 대한 동시화학방사선요법은 대체로 만족할 만한 결과를 얻을 수 있었으나 보다 많은 환자들을 대상으로 하는 장기간의 추적 관찰을 요한다.