• Journal of Digestive Cancer Research
• /
• 제4권1호
• /
• pp.1-9
• /
• 2016

The abundance of multi-drug resistance ATPase binding cassette and deranged self-renewal pathways shown in cancer stem cells (CSCs) played a crucial role in tumorigenesis, tumor resistance, tumor recurrence, and tumor metastasis. Therefore, elucidation of CSCs biology can improve diagnosis, enable targeted treatment, and guide the follow up of GI cancer patients. In order to achieve chemoquiescence, seizing cancer through complete ablation of CSCs, CSCs are rational targets for the design of interventions that will enhance responsiveness to traditional therapeutic strategies and contribute in the prevention of local recurrence as well as metastasis. However, current cancer treatment strategies fail to either detect or differentiate the CSCs from their non-tumorigenic progenies mostly due to the absence of specific biomarkers and potent agents to kill CSCs. Recent advances in knowledge of CSCs enable to produce several candidates to ablate CSCs in gastrointestinal (GI) cancers, especially cancers originated from inflammation-driven mutagenesis such as Barrett's esophagus (BE), Helicobacter pylori-associated gastric cancer, and colitis-associated cancer (CAC). Our research teams elucidated through revisiting old drugs that proton pump inhibitor (PPI) and potassium competitive acid blocker (p-CAB) beyond authentic acid suppression, chloroquine for autophage inhibition, sonic hedgehog (SHH) inhibitors, and Wnt/β-catenin/NOTCH inhibitor can ablate CSCs specifically and efficiently. Furthermore, nanoformulations of these molecules could provide an additional advantage for more selective targeting of the pathways existing in CSCs just like current molecular targeted therapeutics and sustained action, while normal stem cells intact. In this review article, the novel approach specifically to ablate CSCs existing in GI cancers will be introduced with the introduction of explored mode of action.

• Molecules and Cells
• /
• 제46권10호
• /
• pp.579-588
• /
• 2023

Sarcomas are rare and heterogeneous mesenchymal neoplasms originating from the bone or soft tissues, which pose significant treatment challenges. The current standard treatment for sarcomas consists of surgical resection, often combined with chemo- and radiotherapy; however, local recurrence and metastasis remain significant concerns. Although immunotherapy has demonstrated promise in improving long-term survival rates for certain cancers, sarcomas are generally considered to be relatively less immunogenic than other tumors, presenting substantial challenges for effective immunotherapy. In this review, we examine the possible opportunities for sarcoma immunotherapy, noting cancer testis antigens expressed in sarcomas. We then cover the current status of immunotherapies in sarcomas, including progress in cancer vaccines, immune checkpoint inhibitors, and adoptive cellular therapy and their potential in combating these tumors. Furthermore, we discuss the limitations of immunotherapies in sarcomas, including a low tumor mutation burden and immunosuppressive tumor microenvironment, and explore potential strategies to tackle the immunosuppressive barriers in therapeutic interventions, shedding light on the development of effective and personalized treatments for sarcomas. Overall, this review provides a comprehensive overview of the current status and potential of immunotherapies in sarcoma treatment, highlighting the challenges and opportunities for developing effective therapies to improve the outcomes of patients with these rare malignancies.

• BMB Reports
• /
• 제57권2호
• /
• pp.71-78
• /
• 2024

Melanoma is one of the most aggressive skin tumors, and conventional treatment modalities are not effective in treating advanced melanoma. Although immunotherapy is an effective treatment for melanoma, it has disadvantages, such as a poor response rate and serious systemic immune-related toxic side effects. The main solution to this problem is the use of biological materials such as hydrogels to reduce these side effects and amplify the immune killing effect against tumor cells. Hydrogels have great advantages as local slow-release drug carriers, including the ability to deliver antitumor drugs directly to the tumor site, enhance the local drug concentration in tumor tissue, reduce systemic drug distribution and exhibit good degradability. Despite these advantages, there has been limited research on the application of hydrogels in melanoma treatment. Therefore, this article provides a comprehensive review of the potential application of hydrogels in melanoma immunotherapy. Hydrogels can serve as carriers for sustained drug delivery, enabling the targeted and localized delivery of drugs with minimal systemic side effects. This approach has the potential to improve the efficacy of immunotherapy for melanoma. Thus, the use of hydrogels as drug delivery vehicles for melanoma immunotherapy has great potential and warrants further exploration.

• IMMUNE NETWORK
• /
• 제23권4호
• /
• pp.34.1-34.15
• /
• 2023

Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.

• Clinical Endoscopy
• /
• 제56권2호
• /
• pp.239-244
• /
• 2023

Tuberculosis is an adverse event in patients with Crohn's disease receiving anti-tumor necrosis factor (TNF) therapy. However, tuberculosis presenting as a bronchoesophageal fistula (BEF) is rare. We report a case of tuberculosis and BEF in a patient with Crohn's disease who received anti-TNF therapy. A 33-year-old Korean woman developed fever and cough 2 months after initiation of anti-TNF therapy. And the symptoms persisted for 1 months, so she visited the emergency room. Chest computed tomography was performed upon visiting the emergency room, which showed BEF with aspiration pneumonia. Esophagogastroduodenoscopy with biopsy and endobronchial ultrasound with transbronchial needle aspiration confirmed that the cause of BEF was tuberculosis. Anti-tuberculosis medications were administered, and esophageal stent insertion through endoscopy was performed to manage the BEF. However, the patient's condition did not improve; therefore, fistulectomy with primary closure was performed. After fistulectomy, the anastomosis site healing was delayed due to severe inflammation, a second esophageal stent and gastrostomy tube were inserted. Nine months after the diagnosis, the fistula disappeared without recurrence, and the esophageal stent and gastrostomy tube were removed.

• Journal of Korean Neurosurgical Society
• /
• 제30권3호
• /
• pp.334-341
• /
• 2001

Objective : We have currently changed treatment strategies to methotrexate(MTX)-based preirradiation chemotherapy with subsequent planned radiation for the initial therapy of primary central nervous system lymphoma (PCNSL). The aim of this study was to evaluate the results of treating PCNSL with chemotherapy plus radiotherapy (CRT) or radiotherapy(RT) alone. Method and Material : This study involved 10 females and 3 males patients with a mean age of 54.2 years. All patients underwent surgery, open(8 cases) or stereotactic biopsy(5 cases) for histological diagnosis. Eleven tumors were diffuse large B-cell lymphomas. Tumor volume change in the follow-up images and survival time were evaluated in patients treated with CRT and RT alone. In the beginning, two patients received ProMACE-Cytabom chemotherapeutic regimen, but did not complete the course and died of progressive tumor 8 and 9 months after diagnosis, respectively. One patient died at 6 months before chemotherapy. These three were excluded from the survival analysis. Five patients(RT group) completed full courses of cranial irradiation with or without boost. For the current combined modality treatment, high-dose MTXbased chemotherapy(systemic and intrathecal MTX, IV vincristine, and oral procarbazine) followed by whole brain irrdiation to 45Gy to tumor was introduced in 5 patients of CRT group. Result : A complete response was achieved in three of five who received RT only and in all of five who received CRT. All patients in CRT groups are in disease free status at a mean 23 months following therapy. The RT group patients refused any additional salvage therapy at tumor relapse and survived at mean 20 months from diagnosis. The Karnofsky performance status improved in eight of ten patients with treatment. The treatment toxicity included leukoencephalopathy in RT group and severe leukopenia, transient hepatitis, avascular necrosis of femoral head, hearing loss, and amenorrhea in CRT group, respectively. Conclusion : The combined modality therapy of MTX-based chemotherapy plus radiotherapy for PCNSL may enhance tumor response and improve patient survival. The patients who received CRT should be carefully followed up because of the higher risk of treatment-induced late neurotoxicity.

• 한국멀티미디어학회논문지
• /
• 제13권7호
• /
• pp.1044-1050
• /
• 2010

내시경 초음파는 초음파 진동자를 내시경 끝에 부착하여 그 주위의 장기를 관찰할 목적으로 개발된 의료기기이다. 내시경 초음파 검사는 점막하 종양을 직접 관찰 할 수 있어 종양의 병리 소견이 예측 가능하지만, 종양의 악성화 여부 등에 대해 주관적인 소견이 개입될 수 있는 문제점이 있다. 따라서 본 논문에서는 주관적인 소견으로 인해 나타나는 문제점을 객관화하여 질병의 정확도와 재현성을 높이기 위해 종양의 각 특징을 분석하는 방법을 제안한다. 제안된 방법을 적용하기 위해서 내시경 초음파 검사로 얻어진 초기 영상에서 분석에 필요한 초음파 영역을 추출한다. 초음파 영역은 여러 요인으로 인하여 명암도 값의 차이가 발생하는데, 이는 객관적인 분석에는 비효율적이다. 따라서 초기 검사 시에 매질로써 주입되는 물 영역의 명암도를 기준으로 하여 초음파 영역의 명암도를 표준화 한다. 표준화된 초음파 영역에서 전문의에 의하여 선택된 종양 영역에 LVQ 알고리즘과 비트 평면 분할 방법을 각각 적용하여 에코가 높은 spot 영역과 칼슘이 침착된 영역을 추출하고 분석한다. 종양 영역의 세밀한 분석을 위하여 명암도 값과, 종양 영역 내에서 전문의가 임의로 선택한 두 지점의 거리에 포함된 명암도 정보를 추출한다. 또한 선택된 종양의 악성도를 구분하기 위하여 종양 영역에서 외곽의 기울기를 계산한다. 내시경 초음파 영상에서 각 질병의 특징을 분석한 결과, 제시된 방법이 종양이 가지는 특징을 분석하는데 도움이 되는 것을 확인할 수 있었다.

• 생명과학회지
• /
• 제26권9호
• /
• pp.1088-1096
• /
• 2016

중등도 온열요법이 종양세포에 대한 세포독성, 종양혈관에 미치는 영향 및 면역학적 영향 등 다양한 항종양 활성을 가지고 있음에도 불구하고, 중등도 온열요법은 그 자체만으로는 항암효과가 뚜렷하지 않아, 방사선치료나 항암제 치료와 병용하여 암치료에 사용되고 있으면서, 심각한 부작용이 없이 어느 정도의 긍정적인 효과를 보이고 있다. 모든 연구에서 긍정적인 결과를 보이지 못한 것은 열충격 반응 그 자체가 온열요법의 항암효과를 방해하기 때문이다. 그러므로 온열요법의 효과를 증가시키기 위해서는 온열요법의 항암효과에 대한 부정적인 영향을 제거해야 한다. 암세포뿐만 아니라 혈관, 면역 세포 및 결체조직 등을 포함하고 있는 종양조직의 열 스트레스에 대한 반응은 매우 복잡하지만, 임상적으로 사용되고 있는 약물 중 열 스트레스 반응을 조절할 수 있는 약물들이 암환자의 온열요법 치료 효과를 개선시킬 수 있는 지에 대한 연구가 필요하다. 이 종설에서는 현재 임상에서 사용하고 있는 온열요법 장치로서 최신의 기술이며, 중등도 온도가 정상 조직에 대한 부작용 없이 기존 치료법의 효과를 증가시킬 수 있기 때문에, 비침습적 체외용 고주파 중등도 온열요법을 중심으로 다룬다.

• Journal of Chest Surgery
• /
• 제43권4호
• /
• pp.375-380
• /
• 2010

배경: 심장의 원발성 종양은 아주 드문 질환이다. 이중 대부분의 경우는 양성인 점액종이고 이는 조기의 수술적인 치료로 거의 완치되는 반면 육종과 같은 악성종양은 수술적 제거가 어렵고 예후도 안 좋은 것으로 알려져 있다. 본원에서는 심장 종양으로 수술적인 치료를 했던 환자를 모아서 분석해 보았다. 대상 및 방법: 1993년 8월부터 2008년 12월까지 심장 종양으로 수술적인 치료를 하였던 28명의 환자를 대상으로 의무 기록 검토를 통한 후향적 분석을 하였다. 결과: 환자의 연령은 20세에서 76세 사이로 평균 $54.2{\pm}15.6$세였다. 남자가 11명(39%), 여자가 17명(61%)이었다. 15예(54%)에서 심부전의 증상 호전을 위해 응급 수술을 시행하였다. 술 전 주 증상은 호흡곤란이 15예(54%)로 제일 많았다. 전 환자에서 술 전 심장초음파로 진단이 되었다. 수술 시 종양의 크기는 장축이 2∼40 cm의 범위로 평균 $7.0{\pm}6.9$ cm였으며 종양의 부착부위는 18예(64%)에서 심방중격에, 9예(32%)에서 좌심방에, 2예(7%)에서 승모판막윤에, 2예(7%)에서 좌심실에 위치하고 있었다. 수술은 전 환자에서 양 심방절개를 통해 접근하였고 25예(89%)에서 완전절제가 가능하였다. 조직검사에서 육종이 4예(14%), 지방종이 1예(4%), 점액종이 23예(82%)였으며 완전절제를 못했던 3예는 모두 육종이었다. 술 후 사망은 없었다. 외래 추적은 24예(86%)에서 가능했으며 평균 추적 기간은 $46.8{\pm}42.7$개월이었다. 추적 환자 중 만기 사망은 조직검사에서 육종이었던 3명이 있었다. 육종으로 수술했던 환자로 재발 혹은 타 조직으로 전이하여 1예에서 2차례 재수술, 1예에서 전이 부위 절제술, 1예에서는 항암치료만을 했던 환자였다. 평균 재발 및 전이기간은 각각 $12.7{\pm}10.8$개월, $20.5{\pm}16.8$개월이었다. 결론: 심장 종양의 대부분인 점액종은 색전 등의 위험을 야기할 수 있으므로 조기에 수술함이 원칙이고 수술적 제거로 근본적인 치료가 가능하다. 악성종양인 육종은 발견 시 이미 상당히 진행되어 있는 경우가 많고 주위 조직으로의 침윤이 심해 수술적인 제거가 어려운 경우가 많다. 그러나 심부전 증상 등의 증상완화를 위해서는 가능한 부위의 절제를 함으로써 환자의 향후 삶의 질을 높일 수 있는 방편으로 보인다.

• Radiation Oncology Journal
• /
• 제30권4호
• /
• pp.205-212
• /
• 2012

Purpose: To evaluate the effect of pelvic radiotherapy (RT) in patients with stage IV rectal cancer treated with resection of primary tumor with or without metastasectomy. Materials and Methods: Medical records of 112 patients with stage IV rectal cancer treated with resection of primary tumor between 1990 and 2011 were retrospectively reviewed. Fifty-nine patients received synchronous or staged metastasectomy whereas fifty-three patients did not. Twenty-six patients received pelvic radiotherapy. Results: Median overall survival (OS), locoregional recurrence-free survival (LRFS), and progression-free survival (PFS) of all patients was 27, 70, and 11 months, respectively. Pathologic T (pT), N (pN) classification and complete metastasectomy were statistically significant factors in OS (p = 0.040, 0.020, and 0.002, respectively). RT did not improve OS or LRFS. There were no significant factors in LRFS. pT and pN classification were also significant prognostic factors in PFS (p = 0.010 and p = 0.033, respectively). In the subgroup analysis, RT improved LRFS in patients with pT4 disease (p = 0.026). The locoregional failure rate of the RT group and the non-RT group were 23.1% and 33.7%, showing no difference in the failure pattern of both groups (p = 0.260). Conclusion: Postoperative pelvic RT did not improve LRFS of all metastatic rectal cancer patients; however, it can be recommended to patients with pT4 disease. A complete resection of metastatic masses should be performed if possible.