• 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.

• 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.

• Korean Journal of Radiology
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• 제24권7호
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• pp.606-625
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• 2023

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6585-6590
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• 2013

Background: Although FOLFOX (infusional fluorouracil/leucovorin plus oxaliplatin) is established as a standard chemotherapeutic regimen, the long term efficacy of adjuvant XELOX (oral capecitabine plus intravenous oxaliplatin) in Asian colorectal cancer (CRC) patients remains anecdotal. Moreover, uncertainties persist as to whether pharmacogenetic differences in Asian populations preclude equally tolerable and effective administration of these drugs. Method: One hundred consecutive patients with resected colorectal cancer received adjuvant XELOX (oxaliplatin 130 $mg/m^2$ on day 1 plus capecitabine 900 $mg/m^2$ twice daily on day 1 to 14 every 3 weeks for 8 cycles) at Queen Mary Hospital, Hong Kong. Endpoints monitored during follow-up were disease-free survival (DFS) and disease recurrence, overall survival (OS) and adverse events (AEs). Results: The median patient age was 56 years, 56% were diagnosed with rectal cancer and 44% with colonic cancer. After a median follow-up of 4.3 years (95% confidence interval, 3.2-4.7), 24 recurrences were confirmed including 13 patients who died due to progressive disease. Four-year DFS was 81% in colon cancer patients and 67% in rectal cancer patients (p=0.06 by log-rank test). For the cohort as a whole, OS was 90% at 3 years and 84% at 5 years. Treatment-related AEs led to early withdrawal in four patients. The commonest non-hematological AEs were neuropathy (91%), hand-foot syndrome (49%) and diarrhea (46%), while the commonest grade 3/4 AEs were neutropenia (11%) and diarrhea (10%). Conclusion: These results confirm the favourable long term survival benefit with good tolerability in using adjuvant XELOX in treating East Asian colorectal cancer patients.

• 한국식품과학회지
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• 제40권2호
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• pp.207-214
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• 2008

목향(Saussurea lappa)은 항암효과를 비롯하여 다양한 생리활성을 나타내는 것으로 알려지고 있으나 목향이 대장암에 미치는 영향에 대해 자세히 연구된 바가 없다. 본 연구에는 목향 헥산추출물이 인간의 대장에서 유래한 암세포인 HT-29 세포의 증식에 미치는 영향과 그 작용 기전에 대해 연구하였다. 헥산으로 목향을 추출하여 얻은 목향 헥산추출물을 HT-29 세포의 세포 배양액에 0, 1, 3, 5 ${\mu}g/mL$로 첨가하여 세포를 배양하였다. HT-29 세포의 증식은 목향 헥산추출물 처리 농도가 증가할수록 현저히 감소하였다. 인간의 대장에서 유래한 정상 상피세포인 FHC 세포의 증식은 목향 헥산추출물에 의해 변화하지 않았고, 인간의 피부에서 유래한 정상 섬유아세포인 CCD 1108Sk 세포 증식은 목향을 5${\mu}g/mL$ 농도로 72 시간 배양한 경우에만 감소하였다. 목향 헥산 추출물 처리에 의해 HT-29 세포의 세포주기 진행 중 sub G1기에 머무른 세포수가 증가하였고, 세포사멸 세포수가 현저히 증가하였다. 세포사멸의 주요한 조절인자인 Bcl-2 family 단백질 중 Bcl-2은 목향 헥산추출물에 의해 변화하지 않았으나 Bax는 유의적으로 증가하였다. Bcl-2 family 단백질과 더불어 세포사멸 조절에 중요한 역할을 하는 caspases의 활성형인 cleaved caspase-8, -9, -7, -3가 목향 헥산추출물에 의해 증가하였다. 또한 목향 헥산추출물 처리 농도가 증가할수록 cleaved PARP 단백질 수준도 현저히 증가하였다. 이 결과는 목향 헥산추출물이 세포사멸을 유도하여 대장암세포인 HT-29 세포의 증식을 억제함을 나타내며, 목향 헥산추출물에 의해 HT-29 세포의 세포사멸은 Bax 증가와caspases의 활성 증가에 의한 것임을 나타낸다. 본 연구는 목향을 독성과 부작용이 적은 암예방제나 항암제로 개발할 수 있는 가능성을 제시한다. 그러나 목향을 이용하여 제품 개발을 위해서는 유효 성분 동정 및 동물시험 등의 연구 수행이 필요할 것으로 사료된다.

• Journal of Gastric Cancer
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• 제4권4호
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• pp.257-262
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• 2004

목적: 장막침윤이 없는 위암환자에 있어서 수술 후 서로 다른 보조화학요법이 장기 생존에 미치는 영향에 대해 평가하고자 하였다. 대상 및 방법: 1996년 10월부터 1998년 3월까지 만 15개월간 서울 아산병원 외과에서 근치적 위 절제를 시행한 환자 중, 장막침윤이 없는 317명의 환자를 대상으로 하였다. 이중 수술 후 병기가 IA인 131예, 장막침윤이 있는 34예, 그리고 치료를 거부한 17예를 제외한 135명(1군: 5-FU+cisplatin 정주, 2군: mitomycin C정주+경구용5-FU, 3군: 경구용 5-FU)의 의무기록 분석과 전화추적을 실시하여 재발양상, 생존율, 및 위암관련 사망률을 각 군별로 분석하였다. 결과: 121명에서 추적이 가능해 $89.6\%$의 생존율을 나타냈다. 재발은 1군 4명, 2군 7명, 그리고 3군 6명 이었으며, 세 군의 전체생존율은 1군 $89\%$, 2군 $84\%$, 그리고 3군은 $82\%$이고, 위암관련 사망환자만을 고려한 질병특이 생존율은 1군 $92\%$, 2군 $86\%$, 그리고 3군은 $88\%$로 나타나 이들 세 군간에 전체생존율 및 질병특이 생존율은 차이를 보이지 않았다(전체생존율: P=0.6875, 질병특이 생존율: P=0.7120). 결론: 장막침윤이 없는 위암 환자에서, 치료효과를 향상 시키기 위해 보조요법을 시행할 경우 경구용 항암제를 이용한 방법이면 충분하다고 판단하였다. 그러나 이를 입증하기 위해서는 보조요법을 시행치 않는 대조군을 포함한 대단위 무작위 연구가 필수적일 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8377-8382
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• 2014

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. Methods: In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1-oxide induced OSCC. Results: Results showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Conclusion: Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9823-9829
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• 2014

Background: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). Objectives: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). Materials and Methods: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. Results: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan-Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were $43.4{\pm}6.0%$ and $53.2{\pm}6.1%$ respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [$69.8{\pm}10.5%$, $79.8{\pm}9.1%$ for MTX(+) and $31.1{\pm}6.9%$, $42.2{\pm}7.4%$ for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol ($66.7{\pm}13.6%$ and $15.0{\pm}8.0%$ for 3-year DFS, p=0.010, $73.3{\pm}13.2%$ and $20{\pm}8.9%$ for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). Conclusions: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.

• 생명과학회지
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• 제25권11호
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• pp.1235-1243
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• 2015

황흑산은 동의보감의 복강과 장옹의 처방을 위해 기록된 처방전으로 오랫동안 사용되어 왔으나, 항암 효능에 대한 구체적인 연구는 전혀 이루어진 바 없다. 본 연구에서는 AGS 인체 위암세포를 대상으로 황흑산 처리에 의한 증식억제와 연관된 apoptosis 유발 및 관련 기전 연구를 수행하였다. AGS 위암세포에 황흑산 추출물을 처리함에 처리 농도 의존적으로 증식이 억제되었으며, 이는 apoptosis 유발과 연관성이 있음을 핵의 형태적 변형과 sub-G1기 세포의 축적 등으로 확인하였다. 황흑산 추출물에 의한 apoptosis 유도에는 pro-apoptotic Bax 단백질의 발현 증가와 anti-apoptotic Bcl-2의 발현 감소 및 미토콘드리아에서 세포질로의 cytochrome c 유리와 연관성이 있었으며, 세포 내 활성산소종(reactive oxygen species, ROS)의 축적을 증가시켰다. 또한 황흑산 추출물에 의한 apoptosis 유발은 caspases (caspase-3, -8 및 -9)의 활성을 증가시켰으며, poly (ADP-ribose)-polymerase 단백질의 단편화를 초래하였다. 그러나 ROS scavenger 및 pan-caspases inhibitor는 황흑산 추출물에 의한 apoptosis의 유발을 거의 완벽하게 억제하였으며, 암세포의 증식억제도 차단하였다. 이상의 결과는 황흑산 추출물에 의한 apoptosis가 ROS 생성 및 caspase 활성 의존적으로 일어남을 의미하는 것으로 황흑산의 항암기전 해석을 이해하고 향후 지속적인 연구를 위한 유용한 자료로 사용될 것이다.

• Tuberculosis and Respiratory Diseases
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• 제61권2호
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• pp.143-149
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• 2006

연구배경: Toptisomerase I 억제제인 irinotecan 과 소세포폐암 치료의 근간인 cisplatin의 복합화학용법을 확장기 소세포폐암 환자에게 1차 치료법으로 실시하여 반응률, 생존율 및 부작용을 확인하였다. 방 법: 2002년 6월부터 2005년 2월까지 확진된 확장기 소세포폐암 환자 39명에게 irinotecan $60mg/m^2$, 제 1, 8, 15일째 cisplatin $60mg/m^2$ 제1일째에 28일 간격으로 4회 투여하였다. 결 과: 반응률은 77%(완전반응 8%), 중앙생존기간은 14.8개월, 1-및 2-년 생존율은 60.9%, 27.6%였으며, 중앙 무진행생존기간은 8.4개월, 6-및 12-개월 무진행생존율은 75.0%, 18.8%였다. WHO grade 3 이상의 부작용은 백혈구 감소증 23%, 설사 26%였으나, 심한 설사때문에 2명은 치료방법을 바꾸었고, 1명은 사망하였다. 결 론: Irinotecan과 cisplatin 복합화학요법은 확장기 소세포폐암 환자의 1차 치료법으로 유용하며, 부작용으로서 설사에 대해서는 치명적일수 있으므로 심각한 주의가 요망된다.