• Title/Summary/Keyword: Cytotoxic therapy

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Promotion of Nonspecific Cytotoxic T Lymphocyte Activity by Bo-yang-hwan-oh-tang (보양환오탕에 의한 비특이적 세포독성 T 세포 활성 증강)

  • Ha, Jong-Cheon;Kim, Young-Hyun;Woo, Won-Hong;Nam, Sang-Yun
    • Korean Journal of Pharmacognosy
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    • v.32 no.3 s.126
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    • pp.226-232
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    • 2001
  • To explore the possible cancer therapeutic application of "Bo-yang-hwan-oh-tang" (BH), a herbal medicinal recipe used for improvement of blood stasis, we have examined its direct cytotoxicity against tumor cell, and induction of cytotoxic activity of lymphocytes. Water extract of BH alone did not exhibit direct cytotoxicity to Yac-1 target cells even with high concentrations (10 mg/ml). By exposure for 3 days, BH did not induce any nonspecific cytotoxic activity of mouse spleen cells, either, when assessed in a 4 hr $^{51}Cr-release$ assay. However, when BH was added during CD3 stimulation of non-adherent spleen cells, non-specific CTL activity was markedly promoted in a dose dependent manner. In contrast, BH did not alter activated NK cell activity following IL-2 stimulation. These data suggest that BH does not induce but upregulates non-specific CTL effecter function and that activated NK cell does not respond to BH. For elucidation of the mechanism underlying this function of BH, time kinetic study for IL-2 production using ELISA was undertaken. IL-2 production following CD3 stimulation was significantly augmented and higher level of IL-2 is sustained over 3 days in the culture medium by BH treatment. Moreover, addition of exogenous IL-2 during CD3 stimulation resulted in a similar level of cytotoxicity between control and BH-treated culture. These data indicate that the BH-mediated upregulation of non-specific CTL activity is contributed by augmentation of IL-2 production. Our data imply the possible application of BH for combination therapy of cancer with non-specific activator.

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A Comprehensive Review of Diffusing Alpha-Emitters Radiation Therapy (DaRT): From Dosimetry to Its Biological Effectiveness

  • Seohan Kim;Wonmo Sung
    • Journal of Radiation Protection and Research
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    • v.49 no.3
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    • pp.102-113
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    • 2024
  • Diffusing alpha-emitters radiation therapy (DaRT) represents a groundbreaking development in cancer therapy, offering a solution to the limitations of conventional radiation therapy. By deploying 224Ra embedded seeds, DaRT achieves targeted delivery of high-dose alpha particles directly to tumor sites, showing considerable efficacy in tumor control and minimal damage to adjacent healthy tissues. This comprehensive review analyzes the published literature regarding mechanisms, seed production, dose calculation, measurement, and biological experiments related to DaRT. It includes in-depth discussions on mathematical models, Monte Carlo simulations for dose distribution, real-time in vivo dosimetry developments, and biological experiments both in vitro and in vivo. Clinical trial outcomes are also examined to evaluate the therapy's effectiveness in various cancer types. DaRT utilizes 224Ra-labeled seeds, using the decay chain of 224Ra to deliver alpha particles effectively within a tumor. Several asymptotic diffusion-leakage models were developed to calculate the alpha dose distribution of DaRT. In vivo dosimetry techniques have been developed for real-time monitoring. Biological experiments demonstrated the cytotoxic effects of DaRT across various cancer cells, with varying radiosensitivity. Additionally, the enhanced effects of combined therapy with chemotherapy and immunotherapy were suggested by many in vivo studies. Clinical trials have shown high complete response rate in squamous cell carcinoma, with minimal side effects, suggesting DaRT's feasibility and safety. DaRT emerges as a highly localized cancer treatment method with minimal side effects compared to traditional radiation therapy. It directly ablates tumors and potentially enhances immune responses, indicating a significant advance in cancer therapy. Future research and ongoing clinical trials will further elucidate its efficacy across different cancer types and in combination with other treatments.

The Effect of Potassium Cyanate (KCN) on Radiation Treatment of the Colorectal Cancer Cell Line, HCT 116

  • Chang, Jeong Hyun
    • Biomedical Science Letters
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    • v.19 no.2
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    • pp.98-104
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    • 2013
  • Radiation is one of the major therapy for the removal of cancer cells. The results of the radiation therapy depend on the radio-resistance of cancer cells. For the effective treatment in these radio-resistant cancers, the use of chemicals that act on cancer cells is known to enhance the cytotoxic effects of radiation therapy. In this study, I investigated the effect of potassium cyanate (KCN) on the irradiated-colorectal cancer cell line, HCT 116 cells. KCN induces the carbamylation of proteins and can change the biological activity of various human cells. To understand the effect of KCN on the radiosensitivity of HCT 116 cells, I examined alteration of the cell cycle, generation of reactive oxygen species (ROS), cell viability, apoptosis and intracellular signaling proteins in the irradiated cells with/without KCN treatment. Combination treatment caused significant increase in sub $G_0/G_1$ and ROS generation in HCT 116 cells. KCN inhibited the proliferation and cell viability in irradiated HCT 116 cells. KCN-induced apoptosis of irradiated cells was processed via the activation of caspase 3 and caspase 9. Apoptosis-associated signal proteins, including Bax and Bcl-2 were regulated by irradiation with KCN treatment. Taken together, these results may indicate that KCN enhances the radiosensitivity of radio-resistant cell and then has a synergistic effect on radiation therapy in colorectal cancer.

Treatment to induce long-term non-progressor with constant drug dosage (일정한 약물 투여를 통한 HIV 환자의 long-term non-progressor 전환 치료)

  • Kim, Jin-Young;Kim, Won-Hee;Ko, Ji-Hyun;Chung, Chung-Choo
    • Proceedings of the KIEE Conference
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    • 2004.07d
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    • pp.2233-2235
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    • 2004
  • This paper presents a therapy that uses a constant drug dosage for leading a HIV patient to a LTNP (Long-Tenn Non-Progressor). From analysis of CTLp (Cytotoxic T Lymphocyte precursor) concentration at equilibrium point and bifurcation of equilibrium points, we found the therapy with a drug whose efficacy is less than one brings higher CTLp concentration at the equilibrium point. From this fact, we propose a treatment with constant drug dosage. which can induce LTNP.

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Target Therapy for Colorectal Cancer (대장암의 표적치료)

  • Lee, Kyung-Hee
    • Journal of Yeungnam Medical Science
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    • v.23 no.2
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    • pp.143-151
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    • 2006
  • In the past decade, the median duration of survival among patients with advanced colorectal cancer has increased from 12 months to about 18 months, primarily as a results of the introduction of irinotecan and oxaliplatin. Advances in the understanding of the molecular mechanisms underlying the development and progression of cancer have resulted in the discovery of new therapeutic interventions that target specific molecular abnormalities. Their specificity, and therefore their potential to bind preferentially and modify tumor-specific targets, sparing normal tissues and causing fewer side-effects compared to conventional cytotoxic agents, makes them an attractive therapeutic option. The future of this approach for the treatment of solid tumors is promising.

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Treatment for HIV-Infected Patients to Induce Long-Term Non-Progressor with Constant Drug Dosage (일정한 약물 투여를 통한 HIV 감염자의 long-term Non-Progressor 전환 치료)

  • Kim Jinyoung;Kim Won Hee;Ko Ji Hyun;Chung Han Byul;Chung Chung Choo
    • The Transactions of the Korean Institute of Electrical Engineers D
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    • v.54 no.4
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    • pp.259-266
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    • 2005
  • This paper presents a therapy that uses a constant drug dosage for leading HIV-infected patient to LTNP (Long-Term Non-Progressor). Based on analysis of CTLp (Cytotoxic T Lymphocyte precursor) concentration at equilibrium point and its bifurcation, we found the therapy with a drug whose efficacy is less than a certain level brings higher CTLp concentration at the equilibrium point. We observed a treatment with constant drug dosage whose efficacy is less than full treatment may lead HIV-infected patient to LTNP. It turns out that the treatment whose efficacy is less than full treatment is better in the point of performance on controllability.

Chemotherapy for Lung Cancer in the Era of Personalized Medicine

  • Lee, Seung Hyeun
    • Tuberculosis and Respiratory Diseases
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    • v.82 no.3
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    • pp.179-189
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    • 2019
  • Although recent advances in molecular targeted therapy and immuno-oncology have revolutionized the landscape of lung cancer therapeutics, cytotoxic chemotherapy remains an essential component of lung cancer treatment. Extensive evidence has demonstrated the clinical benefit of chemotherapy, either alone or in combination with other treatment modalities, on survival and quality of life of patients with early and advanced lung cancer. Combinational approaches with other classes of anti-neoplastic agents and new drug-delivery systems have revealed promising data and are areas of active investigation. Chemotherapy is recommended as a standard of care in patients that have progressed after tyrosine kinase inhibitors or immune checkpoint inhibitors. Chemotherapy remains the fundamental means of lung cancer management and keeps expanding its clinical implication. This review will discuss the current position and future role of chemotherapy, and specific consideration for its clinical application in the era of precision medicine.

Growth Inhibition of Human Head and Neck Squamous Cell Carcinomas by Angelica decursiva Extracts

  • Shin, Woo-Cheol;Kim, Chun-Sung;Kim, Heung-Joong;Lee, Myoung-Hwa;Kim, Hye-Ryun;Kim, Do-Kyung
    • International Journal of Oral Biology
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    • v.35 no.4
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    • pp.153-158
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    • 2010
  • Angelica decursiva has been used in Korean traditional medicine as an antitussive, an analgesic, an antipyretic and a cough remedy. However, the anti-cancer properties of Angelica decursiva have not yet been well defined. In our current study the cytotoxic activity of ethanol extracts of Angelica decursiva root (EEAD) and the mechanism of cell death exhibited by EEAD were examined in FaDu human head and neck squamous cell carcinoma cells. The cytotoxic effects of EEAD upon the growth of FaDu cells were examined with an MTT assay. In addition, the mechanism of cell death induced by EEAD was evaluated by DNA fragmentation analysis, immunoblotting and caspase activation measurements. EEAD induced apoptotic cell death in FaDu cells in a concentration- and time-dependent manner, as determined by MTT assay and DNA fragmentation analysis. Furthermore, the proteolytic processing of caspase-3, -7 and -9 was increased by EEAD treatment of FaDu cells. In addition, the activation of caspase-3 and -7 was detected in living FaDu cells by fluorescence microscopy. These results suggest that EEAD can induce apoptosis and suppress cell growth in cancer cells and may have utility as a future anticancer therapy.

The Prospective of Antigen-presenting Cells in Cancer Immunotherapy (항원제시세포를 이용한 암 치료제 개발전망)

  • Shim Doo-Hee;Lee Jae-Hwa
    • KSBB Journal
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    • v.19 no.6 s.89
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    • pp.415-420
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    • 2004
  • All around the world, the rate of attack of cancer diseases has been going up and the number of cancer patients has been increasing every year. Cancer can be divided into malignant tumor and benign tumor according to its growth appearance. Many studies and experiments have been conducted and the various treatment are being created to find the way to care malignant. Dendritic cells (DCs), which is an agent of cancer treatments by using an immune reaction in our body, plays an important role to present by a tumor antigen to cytotoxic T-cell and help them to attack the tumor cell directly. However there are some defects of this therapy. Soluble human leukocyte antigen-immunoglobulin fusion protein (HLA-Ig) based artificial antigen presenting cell (aAPC) as the antigen presenting cell (APC) which is complement and overcome some of the limitations of dendritic cell-based vaccines and ex vivo expansion of human T cells is new method for cancer therapy. In this article, we are reviewing the role of DCs and the treatment with it, and searching for the possibility of the new development of immunotherapy for cancer.

Combination Doxorubicin and Interferon-α Therapy Stimulates Immunogenicity of Murine Pancreatic Cancer Panc02 Cells via Up-regulation of NKG2D ligands and MHC Class I

  • Wang, Wen-Jia;Qin, Si-Hao;Zhang, Ji-Wei;Jiang, Yue-Yao;Zhang, Jin-Nan;Zhao, Lei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9667-9672
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    • 2014
  • Background: Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. Materials and Methods: A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-${\alpha}$ (IFN-${\alpha}$) on the ligands of NK and T cells was assessed by flow cytometry. Results: The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) may be a potential strategy for treating pancreatic adenocarcinoma.