• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.261-268
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• 2016

$Foxp3^+$ $CD25^+CD4^+$ regulatory T (Treg) cells are crucial for the maintenance of immunological self-tolerance and are abundant in tumors. Most of these cells are chemo-attracted to tumor tissues and suppress anti-tumor responses inside the tumor. Currently, several cancer immunotherapies targeting Treg cells are being clinically tested. Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. While cisplatin is a powerful drug for the treatment of multiple cancers, there are obstacles that limit its use, such as renal dysfunction and the development of cisplatin-resistant cancer cells after its use. To minimize these barriers, combinatorial therapies of cisplatin with other drugs have been developed and have proven to be more effective to treat cancer. In the present study, we evaluated the effect of the combination therapy using methyl gallate with cisplatin in EL4 murine lymphoma bearing C57BL/6 mice. The combinatorial therapy of methyl gallate and cisplatin showed stronger anti-cancer effects than methyl gallate or cisplatin as single treatments. In Treg cell-depleted mice, however, the effect of methyl gallate vanished. It was found that methyl gallate treatment inhibited Treg cell migration into the tumor regardless of cisplatin treatment. Additionally, in both the normal and cisplatin-treated tumor-bearing mice, there was no renal toxicity attributed to methyl gallate treatment. These findings suggest that methyl gallate treatment could be useful as an adjuvant method accompanied with cisplatin therapy.

• Tuberculosis and Respiratory Diseases
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• 제74권5호
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• pp.226-230
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• 2013

Fetal adenocarcinoma is a rare adenocarcinoma subtype of pulmonary blastoma. A 48-year-old male patient is being referred to our hospital due to progressive dyspnea. A chest X-ray showed a lung mass of unknown origin that was obstructing the right main bronchus. After relieving the airway obstruction with stent insertion via bronchoscopy, a diagnosis of fetal adenocarcinoma is being confirmed through thoracoscopic biopsy. Due to the locally advanced state of the lung cancer, it seemed to be inoperable, and concurrent chemo-radiation therapy was being administered with docetaxel. The stent was removed after improvements in the airway obstruction followed by a lung mass shrinkage. Comparing to other contexts which describe fetal adenocarcinoma as lower grade malignancy with low-associated mortality, herein, we describe a case of locally-advanced fetal adenocarcinoma (T4N3M0). This is the first documented case being treated with concurrent chemoradiation therapy. The followed-up image studies represent a partial response and the patient is currently under further observations.

• BMB Reports
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• 제56권9호
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• pp.482-487
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• 2023

Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we describe the role of KAI1, which is mainly expressed on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs), in niche-mediated LT-HSC maintenance. KAI1 activates TGF-β1/Smad3 signal in LT-HSCs, leading to the induction of CDK inhibitors and inhibition of the cell cycle. The KAI1-binding partner DARC is expressed on macrophages and stabilizes KAI1 on LT-HSCs, promoting their quiescence. Conversely, when DARC+ BM macrophages were absent, the level of surface KAI1 on LT-HSCs decreases, leading to cell-cycle entry, proliferation, and differentiation. Thus, KAI1 acts as a functional surface marker of LT-HSCs that regulates dormancy through interaction with DARC-expressing macrophages in the BM stem cell niche. Recently, we showed very special and rare macrophages expressing α-SMA+ COX2+ & DARC+ induce not only dormancy of LT-HSC through interaction of KAI1-DARC but also protect HSCs by down-regulating ROS through COX2 signaling. In the near future, the strategy to combine KAI1-positive LT-HSCs and α-SMA/Cox2/DARC triple-positive macrophages will improve the efficacy of stem cell transplantation after the ablative chemo-therapy for hematological disorders including leukemia.

• 대한두경부종양학회지
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• 제6권1호
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• pp.11-23
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• 1990

Systemic chemotherapy is usually regarded as the standard treatment for palliation in patients with recurrent or metastatic cancer who have failed the definite local treatment with surgery and/or radiotherapy. Recently, with the introduction of more active chemotherapeutic agents and combinations, systemic chemotherapy is being increasingly used before or after local therapy in patients with previously untreated locally advanced head and neck cancer. The most active agents for the head and neck caner are methotrexate, 5-fluorouracil (5-FU), cisplatin and bleomycin. The overall response rates to each of these four drugs are 15-30% expecially when used as first line therapy. But most of these responses are partial with a mean duration of 3-5 months. Various combinations with methotrexate, 5-FU, cisplatin, and bleomycin have been tried with overall response rates of 50-90%, and 10-20% of complete responses. The introduction of chemotherapy prior to local therapy, induction chemotherapy, has been investigated with improved survivals in patients with complete response, especially pathologic, though improvement in overall survival has not been proved yet after the induction chemotherapy. Other therapeutic modalities, such as 'Sandwich' chemotherapy between surgery and radiotherapy, concomittent chemo-radiotherapy and post local treatment adjuvant chemotherapy have been pursued with some hopeful results but these trials should be compared with prospective randomized Phase III trials. To increase the response rates and enhance the survival, important work still remains; 1. Identification of better prognostic factors, 2. Improvement in staging, 3. Development of more active and safter chemotherapeutic agents, 4. Identification of the proper sequence for the addition of chemotherapy to multimodality treatment, and 5. Testing the value of such chemotherapy in locally advanced cancer patients.

• Clinical Endoscopy
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• 제57권1호
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• pp.112-121
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• 2024

Background/Aims: Since the usefulness of neoadjuvant chemo(radiation) therapy (NAT) for pancreatic cancer has been demonstrated, recurrent biliary obstruction (RBO) in patients with pancreatic cancer with a fully covered self-expandable metal stent (FCSEMS) during NAT is expected to increase. This study investigated the impact of sarcopenia on RBO in this setting. Methods: Patients were divided into normal and low skeletal muscle index (SMI) groups and retrospectively analyzed. Patient characteristics, overall survival, time to RBO (TRBO), stent-related adverse events, and postoperative complications were compared between the two groups. A Cox proportional hazard model was used to identify the risk factors for short TRBO. Results: A few significant differences were observed in patient characteristics, overall survival, stent-related adverse events, and postoperative complications between 38 patients in the normal SMI group and 17 in the low SMI group. The median TRBO was not reached in the normal SMI group and was 112 days in the low SMI group (p=0.004). In multivariate analysis, low SMI was the only risk factor for short TRBO, with a hazard ratio of 5.707 (95% confidence interval, 1.148-28.381; p=0.033). Conclusions: Sarcopenia was identified as an independent risk factor for RBO in patients with pancreatic cancer with FCSEMS during NAT.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.691-694
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• 2014

Background: Tumor length in patients with esophageal cancer (EC) has recently received great attention. However, its prognostic role for EC is controversial. The purpose of our study was to characterize the prognostic value of tumor length in EC patients and offer the optimum cut-off point of tumor length by reliable statistical methods. Materials and Methods: A retrospective analysis was conducted on 71 consecutive patients with EC who underwent surgery. ROC curve analysis was used to determine the optimal cut-off point for tumor length, measured with a handheld ruler after formalin fixation. Correlations between tumor length and other factors were surveyed, and overall survival (OS) rates were compared between the two groups. Potential prognostic factors were evaluated by univariate Kaplan-Meier survival analysis. A P value less than 0.05 was considered significant. Results: There were a total of 71 patients, with a male/female divide of 43/28 and a median age of 59. Characteristics were as follows: squamous/adenocarcinoma, 65/6; median tumor length, 4 (0.9-10); cut-off point for tumor length, 4cm. Univariate analysis prognostic factors were tumor length and modality of therapy. One, three and five year OS rates were 84, 43 and 43% for tumors with ${\leq}4cm$ length, whereas the rates were 75, 9 and 0% for tumors >4 cm. There was a significant association between tumor length and age, sex, weight loss, tumor site, histology, T and N scores, differentiation, stage, modality of therapy and longitudinal margin involvement. Conclusions: Future studies for modification of the EC staging system might consider tumor length too as it is an important prognostic factor. Further assessment with larger prospective datasets and practical methods (such as endoscopy) is needed to establish an optimal cut-off point for tumor length.

• Radiation Oncology Journal
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• 제16권4호
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• pp.433-440
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• 1998

목적 : 소세포폐암은 모든 폐암의 20-25$\%$를 차지하고 있으며 생물학적 특성상 다른 조직암과 달리 빨리 자라고 일찍 전이하는 특성을 가지고 있으며 항암화학요법과 방사선 치료에 잘 반응하나 예후는 극히 나쁘다. 따라서 방사선 치료를 항암화학요법과 병행하여 시행한 환자의 예후인자에 따른 생존율과 실패양상을 분석하고자 한다. 방법 및 대상 : 1985년 8월부터 1996년 12월까지 소세포폐암으로 방사선 치료를 시행한 90명의 환자 중 추적관찰이 가능했던 환자 74명을 대상으로 치료 성적, 예후 인자 및 치료 후 실패 양상을 후향적으로 분석하였다. 환자의 추적 관찰 기간은 4-87개월(중앙값 14개월), 생존자의 최소 추적 관찰 기간은 8개월이었으며, 연령은 27세에서 78세로 연령의 중앙값은 59세였다. 결과 : 전체 환자의 2년 생존율은 13$\%$였으며 생존기간의 중앙값은 10개월이었다. 국한성 병기와 전이성 병기의 2년 생존율은 각각 20$\%$와 8$\%$였으며 중앙 생존 기간은 각각 14개월과 9개월로 통계학적 의미가 있었다(p=0.032). 34명의 국한성 병기를 따로 분석한 결과 반응이 기록된 26명중 완전관해는 22명(88$\%$)이었고 부분 관해는 3명(12$\%$)이었다. 치료 반응에 따른 2년 생존율은 각각 24$\%$와 0$\%$였고 중앙 생존 기간은 14개월과 5개월이었다(p=0.005). 혈장 나트륨의 저하에 따른 분석 결과 혈장 나트륨이 135mmol/L이하인 경우 1년 이내에 모두 사망하였고 135mmol/L 이상인 경우의 2년 생존율은 17$\%$였으며, 중앙 생존 기간은 각각 7개월과 14개월이었다(p=0.002). Alkaline phosphatase(ALP)가 130IU/L 이하와 이상에서 2년 생존율은 각각 26$\%$와 0$\%$였으며 중앙 생존 기간은 14개월과 5개월이었다(0.019). 43명의 전이성 병기를 전이된 부위에 따라 분석한 결과 뇌 전이와 간 전이 기타 부위의 전이의 2년 생존율은 14$\%$와 0$\%$ 그리고 7$\%$였고 중앙 생존 기간은 각각 8개월과 8개월, 7개월이었으나 통계적 의의는 없었다. 국소부위의 치료반응에 따른 2년 생존율은 완전관해와 부분관해에서 각각 15$\%$와 4$\%$였고 중앙 생존 기간은 11개월과 7개월이었으며 통계적 의미가 있었다(p=0.01). 결론 : 국한성 병기와 전이성 병기의 소세포폐암은 완전관해의 여부가 예후에 가장 큰 영향을 주는 요소로 완전관해를 위해 방사선 치료 방법에 있어 조기에 방사선 치료 시행하거나 고분할방사선 치료, 동시항암화학요법과 방사선치료 등의 적절한 치료방법의 정립이 중요하며, 혈청나트륨 값이 의미 있게 낮거나 Alkaline phosphatase 값이 의미 있게 높을 경우에 적극적인 보조요법이 필요하다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2297-2302
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• 2014

Objective: To evaluate early treatment for extranodal natural killer/T cell lymphoma (ENK/TCL) in China and provide reference for clinical treatment of these patients. Methods: Computer-based retrieval was performed in PubMed, CNKI, CBM, VIP and WanFang Data to search for randomized controlled trials (RCTs) of treatment for early ENK/TCL, and a meta-analysis was conducted with RevMan 5.0 software. Results: A total of 11 RCTs, including 871 patients, were selected, of which the first radiotherapy had a higher complete response (CR) than the first chemotherapy [OR=14.16, 95%CI (8.68, 23.10), P<0.00001] and CR was not different between combined treatment group and radiotherapy group [OR=1.86, 95%CI (0.47, 3.58), P=0.61], but long-term survival rate was higher with combined treatment[OR=1.88, 95%CI (1.09, 3.19), P=0.02]. No difference in survival rate was observed between radio-chemotherapy and chemo-radiotherapy groups [OR=1.11, 95%CI (0.73, 1.69), P=0.63]. Conclusions: Radiotherapy is of great significance in the treatment of early ENK/TCL, but combined therapy could further enhance long-term survival rate of patients. This conclusion still requires further confirmation using RCTs with high quality and large sample size.

• Journal of Chest Surgery
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• 제26권12호
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• pp.934-939
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• 1993

Mediastinal lymph node involvement [N2 disease] is generally accepted as an important factor influencing the outcome of patients with lung cancer.The long-term survival rates of completely resected patients with N2 disease are frequently reported from 15% to 30%.To improve the management and the outcome of patients with resectable N2 disease, we analyzed the survival rates and the prognostic factors for resected N2 lung cancer. Between August 1989 and September 1993, we experienced 27 patients with N2 disease of 115 surgically treated lung cancer at the Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, Ulsan University Medical School. Of these 27 N2 disease 4 had only an exploratory thoracotomy, and 23 underwent pulmonary resection by pneumonectomy[15], bilobectomy[3], lobectomy[4] and sleeve lobectomy[1].All of resected 23 patients received postoperative adjuvant chemotherapy[3], radiotherapy[2] or combined chemo-radiotherapy[18].Complete follow-up was obtained in 23 patients and median survival was 22 months and overall 1-year and 2-year survival rates by Kaplan-Meir method were 65 % and 45 %, respectively. Survival differences according to histology, tumor location, number of positive nodal station and operative method were not significant, statistically. Conclusively, we think that in resectable N2 lung cancer, complete tumor resection and mediastinal lymph node dissection, and postoperative adjuvant therapy should be done to improve the survival.

• Journal of Chest Surgery
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• 제29권5호
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• pp.536-541
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• 1996

Between June 1988 and June 1994, twenty five patients with locAlly advanced esophageal carcinoma received preoperative chemotherapy (Cisplatln, 5-Fluorouracil with or without Etoposide) and followed by resection. All patients had clinical evidence of airway involvement or distant Iymphnode involve- ment (M 1 Iymphnode) on bronchoscopy or computed tomographic scans. The major response rate to chemotherapy decided by the postoperative stage was 48% (12125). The resection rate was 92% (23/25) with overall complete resection rate of 72% (18125). Two patients had exploratory laparotomy (thorn- cotomy) only. Thirteen patients had esophagogastrostomy with a combined abdominl and Rt. thoracic approach (Ivor Lewis operation), slx pAtients had transhiatal esophagectomy, four patients had esophagogastrostomy with a combined Rt. thoracotonly & abdominal, cervical approach. There were three postoperative deaths (12%). Follow-up duration was between 3.3 months to 65 months. Median survival ime of resected patients except hospital death was 14.8 months. Actuarial survival at 12, 24 months was 72.9%, 26.2%. Signifi- cant better survival was associated with responder group (postoperative stage less than lIB) (P=0.029). These results demonstrate that 1) Preoperative Cisplatin based combined chemotherapy Produce high response rate, 2) High complete resection rate with acceptable mortality rate occur after preoperative chemotherapy, 3) Better surviL dl can be anticipated if complete resection performed after major re- sponse to preoperative chemotherapy.