• Journal of Chest Surgery
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• 제53권4호
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• pp.160-167
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• 2020

Surgical resection is the mainstay of treatment for locally advanced esophageal cancer. Neoadjuvant therapy is recommended to improve survival, based on the results of several randomized trials and meta-analyses. However, controversy remains regarding how to combine surgery, radiotherapy, and chemotherapy. Moreover, in East Asia, the predominant histological type is esophageal squamous cell carcinoma, which has a different epidemiology and tumor biology from esophageal or gastroesophageal junctional adenocarcinoma. As such, the management of esophageal cancer in East Asia seems to be different from that in Western countries. Thus, this article reviews the current evidence on neoadjuvant therapy and considers the optimal combinations and ongoing strategies of multimodal therapy for esophageal squamous cell carcinoma.

• 한양메디칼리뷰
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• 제33권1호
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• pp.59-64
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• 2013

Cancer remains the leading cause of death worldwide despite intense efforts in developing innovative treatments. Current approaches in cancer therapy are mainly directed to a selective targeting of cancer cells to avoid potential side effects associated with conventional therapy. In this respect, Natural killer (NK) cells have gained growing attention and are now being considered as promising therapeutic tools for cancer therapy owing to their intrinsic ability to rapidly recognize and kill cancer cells, while sparing normal healthy cells. NK cells play a key role in the first line of defense against transformed and virus-infected cells. NK cells sense their target through a whole array of receptors, both activating and inhibitory. Functional outcome of NK cell against target cells is determined by the balance of signals transmitted from diverse activating and inhibiting receptors. Despite significant progress made in the role of NK cells attack as a pivotal sentinel in tumor surveillance, the molecular has been that regulate NK cell responses remain unclear, which restricts the use of NK cells as a therapeutic measure. Accordingly, current efforts for NK cell-based cancer therapy have largely relied on the strategies that are based on the manipulation of inhibitory receptor function. However, if we better understand the mechanisms governing NK cell activation, including those mediated by diverse activating receptors, this knowledge can be applied to the development of optimal design for cancer immunotherapy by targeting NK cells.

• 한국발생생물학회지:발생과생식
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• 제21권1호
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• pp.1-10
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• 2017

The use of human mesenchymal stem cells (hMSCs) in cell-based therapy has attracted extensive interest in the field of regenerative medicine, and it shows applications to numerous incurable diseases. hMSCs show several superior properties for therapeutic use compared to other types of stem cells. Different cell types are discussed in terms of their advantages and disadvantages, with focus on the characteristics of hMSCs. hMSCs can proliferate readily and produce differentiated cells that can substitute for the targeted affected tissue. To maximize the therapeutic effects of hMSCs, a substantial number of these cells are essential, requiring extensive ex vivo cell expansion. However, hMSCs have a limited lifespan in an in vitro culture condition. The senescence of hMSCs is a double-edged sword from the viewpoint of clinical applications. Although their limited cell proliferation potency protects them from malignant transformation after transplantation, senescence can alter various cell functions including proliferation, differentiation, and migration, that are essential for their therapeutic efficacy. Numerous trials to overcome the limited lifespan of mesenchymal stem cells are discussed.

• 한국임상약학회지
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• 제21권4호
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• pp.319-331
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• 2011

Purpose: The purpose of this study is to evaluate current criteria for insurance coverage by Health Insurance Review & Assessment Service (HIRA) on the systemic therapy used in the treatment of advanced or metastatic renal cell carcinoma (RCC), by reviewing all available clinical evidences including a variety of clinical practice guidelines. Methods: We searched clinical databases and collected data from published phase 1 through 3 randomized clinical trials on all systemic therapies used in RCC, including novel targeted therapies. Additionally, current clinical practice guidelines on the management of kidney cancer or RCC were reviewed. Based on the collected data we evaluated the appropriateness of the HIRA criteria for insurance coverage on the systemic therapy of RCC whether they are evidence-based and up to date. Results: On the basis of the collected data we concluded that there was a need for a revision in HIRA criteria for systemic therapy of RCC. Despite recent emerging therapeutic advances and changes in therapeutic strategies of management of RCC, some of anticancer regimens were inappropriately listed even though they were not proven to provide efficacy or safety superior to those of other therapies. We thus proposed an updated recommendation based on current clinical evidences. Conclusion: Systemic therapy of RCC is being rapidly changed with the advancement of understanding of the molecular biology of cancer. Consequently newly developed targeted therapies are becoming the standard therapy in the management of medically or surgically unresectable advanced or metastatic RCC. To provide effective and safe therapy to patients with RCC, the criteria for insurance coverage should be made carefully taking into consideration of most up-to-date and high-quality clinical evidences, and should be continuously reviewed so as to reflect evidence-based clinical practice.

• International Journal of Stem Cells
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• 제16권1호
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• pp.16-26
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• 2023

Despite long-term research achievements, the development of cell therapy (CT) products remains challenging. This is because the risks experienced by the subject and therapeutic effects in the clinical trial stage are unclear due to the various uncertainties of CT when administered to humans. Nevertheless, as autologous cell products for systemic administration have recently been approved for marketing, CT product development is accelerating, particularly in the field of unmet medical needs. The human experience of CT remains insufficient compared with other classes of pharmaceuticals, while there are countless products for clinical development. Therefore, for many sponsors, understanding the rationale of human application of an investigational product based on the consensus and improving the ability to apply it appropriately for CT are necessary. Thus, defining the level of evidence for safety and efficacy fundamentally required for initiating the clinical development and preparing it using a reliable method for CT. Furthermore, the expertise should be strengthened in the design of the first-in-human trial, such as the starting dose and dose-escalation plan, based on a sufficiently acceptable rationale. Cultivating development professionals with these skills will increase the opportunity for more candidates to enter the clinical development phase.

• IMMUNE NETWORK
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• 제5권1호
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• pp.36-44
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• 2005

Background: The anti-tumor therapeutic effect of autologous tumor cell lysate pulseddendritic cells (DCs) was studied for non-immunogenic and immune suppressive lung cancer model. To test the possibility as an adjuvant therapy, minimal residual disease model was considered in mouse in vivo experiments. Methods: Syngeneic 3LL lung cancer cells were inoculated intravenously into the C57BL/6 mouse. Autologous tumor cell (3LL) or allogeneic leukemia cell (WEHI-3) lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, tumor formation in the lung and the tumor-specific systemic immunity were observed. Tumor-specific lymphocyte proliferation and the IFN-${\gamma}$ secretion were analyzed for the immune monitoring. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with tumor cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor formation was suppressed in 3LL tumor cell lysate pulsed-DC treated group, while 3LL-specific immune stimulation was minimum. WEHI-3-specific immune stimulation occurred in WEHI-3 lysate-pulsed DC treated group, which had no correlation with tumor regression. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs as an adjuvant therapy for minimal residual disease state of lung cancer. The significance of immune modulation in DC therapy including the possible involvement of NK cell as well as antigen-specific cytotoxic T cell activity induction was discussed.

• 대한임상검사과학회지
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• 제56권1호
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• pp.1-9
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• 2024

엑소좀은 나노 크기의 세포외 소포체로 핵산, 단백질, 지질 등 다양한 생리활성 물질을 함유하고 있다. 엑소좀의 생리활성 물질들은 주변 세포나 조직으로 전달될 수 있을 뿐만 아니라 기원된 세포의 고유 특정 물질들을 지니고 있기 때문에 엑소좀 유래 물질들은 진단 및 치료를 위한 도구로 광범위하게 사용될 수 있음이 입증되고 있으며, 이러한 이유로 엑소좀은 진단을 위한 바이오마커, 약물 전달을 위한 운반체 및 치료제로 활용될 수 있는 가능성에 많은 연구자들의 관심이 높아지고 있다. 줄기세포 분야에서 엑소좀은 줄기세포를 기반으로 한 비세포 치료제로서 보다 안전한 치료제로 사용될 수 있다는 점에서 매력적인 소재가 되고 있으며, 최근에는 중간엽줄기세포 유래 엑소좀이 항염증 및 면역조절능이 있어 코로나-19 증상 완화 효능에 대한 안전성과 효능이 입증되기도 했다. 이렇게 계속적인 엑소좀에 대한 축적된 연구는 임상 진단 및 치료를 위한 차세대 혁신적 결과물들을 제공할 것으로 생각되며, 이 종설에서는 엑소좀의 다양한 가치에 초점을 두고 미래의학의 강력한 도구로 어떻게 활용될 수 있는지에 대한 엑소좀의 잠재력을 살펴보고자 한다.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2009년도 특별 Symposium
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• pp.20-21
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• 2009

• BMB Reports
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• 제48권4호
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• pp.193-199
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• 2015

Degenerative retinal diseases affect millions of people worldwide, which can lead to the loss of vision. However, therapeutic approaches that can reverse this process are limited. Recent efforts have allowed the possibility of the stem cell-based regeneration of retinal cells and repair of injured retinal tissues. Although the direct differentiation of pluripotent stem cells into terminally differentiated photoreceptor cells comprises one approach, a series of studies revealed the intrinsic regenerative potential of the retina using endogenous retinal stem cells. Muller glial cells, ciliary pigment epithelial cells, and retinal pigment epithelial cells are candidates for such retinal stem cells that can differentiate into multiple types of retinal cells and be integrated into injured or developing retina. In this review, we explore our current understanding of the cellular identity of these candidate retinal stem cells and their therapeutic potential for cell therapy against degenerative retinal diseases. [BMB Reports 2015; 48(4): 193-199]

• Biomolecules & Therapeutics
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• 제31권5호
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• pp.559-565
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• 2023

Ataxia-telangiectasia mutated (ATM), a master kinase of the DNA damage response (DDR), phosphorylates a multitude of substrates to activate signaling pathways after DNA double-strand breaks (DSBs). ATM inhibitors have been evaluated as anticancer drugs to potentiate the cytotoxicity of DNA damage-based cancer therapy. ATM is also involved in autophagy, a conserved cellular process that maintains homeostasis by degrading unnecessary proteins and dysfunctional organelles. In this study, we report that ATM inhibitors (KU-55933 and KU-60019) provoked accumulation of autophagosomes and p62 and restrained autolysosome formation. Under autophagy-inducing conditions, the ATM inhibitors caused excessive autophagosome accumulation and cell death. This new function of ATM in autophagy was also observed in numerous cell lines. Repression of ATM expression using an siRNA inhibited autophagic flux at the autolysosome formation step and induced cell death under autophagy-inducing conditions. Taken together, our results suggest that ATM is involved in autolysosome formation and that the use of ATM inhibitors in cancer therapy may be expanded.