• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4329-4333
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• 2015

Background: To investigate the change of frequency and immuno-inhibitory function of myeloid-derived suppressor cells (MDSCs) after treatment of cisplatin (DDP) in A375 human melanoma model. Materials and Methods: BALB/c nude mice were inoculated with A375 cells to establish the human melanoma model and randomly divided into control group given normal saline (NS) and experimental group treated with DDP (5 mg/kg). The percentages of MDSCs in the tumor tissue and peripheral blood after DDP treatment were detected by flow cytometry. The proliferation and interferon-${\gamma}$ (IFN-${\gamma}$) secretion of T cells co-cultured with MDSCs were analyzed through carboxyfluorescein succinimidyl ester (CFSE) labeling assay and enzyme-linked immunospot (ELISPOT) assay, respectively. Results: In A375 human melanoma model, DDP treatment could significantly decrease the percentage of MDSCs in the tumor tissue, but exerted no effect on the level of MDSCs in peripheral blood. Moreover, DDP treatment could attenuate the immuno-inhibitory function of MDSCs. T cells co-cultured with DDP-treated MDSCs could dramatically elevate the proliferation and production of INF-${\gamma}$. Conclusions: DDP can decrease the frequency and attenuate immuno-inhibitory function of MDSCs in A375 melanoma model, suggesting a potential strategy to augment the efficacy of combined immunotherapy.

• Korean Journal of Clinical Pharmacy
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• v.21 no.4
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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.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.265-274
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• 2002

Background : Tumor associated antigens, which are produced specifically by tumor cells, are promising targets for the early diagnosis and immunotherapy. Among the tumor associated antigens, MAGE (a melanoma antigen), BAGE, GAGE, PRAME and NY-ESO were named as cancer/testis specific antigens they are detected exclusively in the testis or cancer cells If MAGE is easily detectable in the sputum, it would become a convenient method for diagnosing lung cancer. This study was undertaken to investigate MAGE expression in the induced sputum obtained from lung cancer patients. Materials and Methods : In 14 control patients and 30 lung cancer patients, the induced sputum was collected after inhaling 3% saline(5 cc) delivered by nebulizer for approximately 5 minutes after a mouth rinse and bronchodilator inhalation. The induced sputum was placed in a conservative-mixed solution (guanidinium isothiocyanate, Triton X-100). The total cellular mRNA was extracted from the cells and RT PCR and nested PCR were run in 30 and 35 cycles respectively, with two different types of primers specially designed to detect six subtypes of MAGE DNA simultaneously. Results : MAGE expression was not detected in the 14 controls, but in the 30 cancer patients, MAGE was found in 24 patients (80%, p=0.001). In the cancer patients, there were no differences in the expression level according to the tissue types (squamous cell cancer 13/17, adenocarcinoma 7/9, and small cell cancer 4/4, p-0.56). Among the 24 MAGE-positive patients, the tumor was not visible on a bronchoscopy in 11 patients (45.8%). Conclusion : A study of MAGE in induced sputum appears to be a useful and complementary method in the diagnosis of lung cancer. A further prospective study with more patients is recommended.

• Food Science and Biotechnology
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• v.14 no.4
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• pp.479-486
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• 2005

Arabinoxylan, a complex polysaccharide in cereal cell walls, has recently received research attention as a biological response modifier. The immunomodulating effect of arabinoxylans from rice bran (AXrb) was studied using a combined process of extrusion and commercial hemicellulase treatment in order to elucidate the augmentation mechanism of cell-mediated immunity in vitro. The cytotoxicity of mouse spleen lymphocytes against YAC-1 tumor cells was significantly enhanced by treatment with AXrb at $10-100\;{\mu}g/mL$. In an attempt to investigate the mechanism by which AXrb enhance NK cytotoxicity, we examined the effect of AXrb on cytokine production by spleen lymphocytes. Culture supernatants of the cells incubated with AXrb were collected and analyzed for IL-2 and IFN-${\gamma}$ synthesis by ELISA. IL-2 and IFN-${\gamma}$ production were increased significantly. These results suggest that AXrb may induce Th1 immune responses. Macrophages play an important role in host defenses against tumors by killing them and producing secretory products, which protect against bacterial, viral infection and malignant cell growth. AXrb were examined for their ability to induce secretory and cellular responses in murine peritoneal macrophages. When macrophages were treated with various concentrations ($10-100\;{\mu}g/mL$) of AXrb, AXrb induced tumoricidal activity, as well as increasing phagocytosis and the production of NO, $H_2O_2$, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. These results indicate that reactive oxygen species, reactive nitrogen species, and inflammatory cytokines are likely to be the major mediators of tumoricidal activity in AXrb-treated macrophages. Therefore, AXrb may be useful in cancer immunotherapy and it is anticipated that AXrb obtained using extrusion and subsequent enzyme treatment can be used as an ingredient in nutraceuticals and cereal-based functional food.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.266-276
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• 2002

A red ginseng acidic polysaccharide(RGAP) with immunomodulating antitumor activities was isolated from Korean red ginseng, The molecular weight of RGAP was estimated to be 12-450 kDa by gel filtration chromatography, RGAP was found to increase survival rate and to inhibit of tumor growth significantly in a dose dependent manner in mice transplanted with tumor cells. RGAP significantly promoted nitric oxide(NO) production from peritoneal macrophages bothin vivo and in vitro. Western blot analysis exhibited a newly synthesized inducible nitric oxide synthase(iNOS) protein band in the RGAP treated group. It seems likely that immunomodulating antitumor activities of RGAP are mainly mediated by NO production of macrophage. RGAP was further purified by ultrafiltration and anion exchange chromatography on DEAE-sepharose, followed by gel filtration on Sephacryl S-300 to give an active fraction(GFP) with stronger NO production in murine macrophages. GFP increased survival rate ten times compared to RGAP in male ICR mice transplanted with sarcoma 180 and also showed more potent tumoricidal activities of natural killer cells than RGAP. Sugar $composition(mol\%)$ of GFP was found to be arabinose:rhamnose:xylose:galacturonic acid:mannose:galactose:glucose(10:9:1:25:8:20:27) by GC/MS. The results suggest that clinical trials of RGAP in immunotherapy against cancer are highly feasible.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4031-4036
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• 2012

Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5825-5831
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• 2013

Background/Objectives: Maintenance of cellular function in culture is vital for transfer and development following adoptive immunotherapy. Dual properties of IL-21 in activating T cells and reducing activation induced cell death led us to explore the mechanism of action of IL-21 enhanced proliferation and cytotoxic potential of CIK cells. Method: CIK cells cultured from PBMCs of healthy subjects were stimulated with IL-21 and cellular viability and cytotoxicity to K562 cells were measured. To elucidate the mechanism of action of IL-21, mRNA expression of cytotoxic factors was assessed by RT-PCR and protein expression of significantly important cytotoxic factors and cytokine secretion were determined through flow cytometry and ELISA. Western blotting was performed to check the involvement of the JAK/STAT pathway following stimulation. Results: We found that IL-21 did not enhance in vitro proliferation of CIK cells, but did increase the number of cells expressing the CD3+/CD56+ phenotype. Cytotoxic potential was increased with corresponding increase in perforin ($0.9831{\pm}0.1265$ to $0.7592{\pm}0.1457$), granzyme B ($0.4084{\pm}0.1589$ to $0.7319{\pm}0.1639$) and FasL ($0.4015{\pm}0.2842$ to $0.7381{\pm}0.2568$). Interferon gamma and TNF-alpha were noted to increase ($25.8{\pm}6.1ng/L$ to $56.0{\pm}2.3ng/L$; and $5.64{\pm}0.61{\mu}g/L$ to $15.14{\pm}0.93{\mu}g/L$, respectively) while no significant differences were observed in the expression of granzyme A, TNF-alpha and NKG2D, and NKG2D. We further affirmed that IL-21 signals through the STAT-3 and STAT-5b signaling pathway in the CIK cell pool. Conclusion: IL-21 enhances cytotoxic potential of CIK cells through increasing expression of perforin, granzyme B, IFN-gamma and TNF-alpha. The effect is brought about by the activation of STAT-3 and STAT-5b proteins.

• KSBB Journal
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• v.23 no.2
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• pp.109-117
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• 2008

Phellinus linteus (Sang Hwang mushroom; P. linteusis) has been widely used for a traditional medicine in Japan, Korea and China. In traditional oriental applications, P. linteus and their extracts have been exclusively used to treat various diseases like insomnia, neurasthenia, gastric ulcers, arthritis, nephritis, stress, asthma, bronchitis, neuromuscular disorders, hypertension and also as an immune system stimulator in cancer therapy. In a number of articles, it is indicated how tremendous their therapeutic values are. According to these studies, P. linteus and their extracts show immunomodulatory activities like enhancing immune system function including anti-tumor activity and inhibiting the growth of existing tumors. P. linteus and their extracts have been being studied for use as immunotherapy agents and biological response modifiers (BRMs) for the possible treatment of cancer without side effects. Recently, the cultured mycelium product of P. linteus has been developed and approved as a medicine in Korea. This review shows not only the current status of methods of developmental technology like artificial culture and various biological applications of P. linteus but also recent market trends of functional foods made from P. linteus.

• Journal of Digestive Cancer Research
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• v.3 no.2
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• pp.82-88
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• 2015

Gastric lymphoma comprises 1-6% of all gastric malignant neoplasms and among them 50% is gastric MALT lymphoma. The 60-70% of MALT lymphomas is diagnosed at early, localized diseased state. Gastric MALT lymphoma is assumed that it progress slowly with indolent course. It presents nonspecific symptoms such as epigastric pain, dyspepsia, nausea and vomiting. It is rarely associated with serious complication such as gastrointestinal bleeding or perforation. The definite diagnosis of gastric MALT lymphoma should be made with histopathologically. Wotherspoon score is used to differential diagnosis with Helicobacter pylori associated gastric inflammatory change. Gastric MALT lymphoma is associated with Helicobacter pylori infection with supported by epidemiologic and histopathologic studies. Gastric MALT lymphoma is characterized with genetic aberrations such as trisomy 3, trisomy 18, chromosomal translocations t(11;18), t(1;14), t(14;18), t(3;14). Appropriate clinical staging is essential to determine the optimal treatment strategy for gastric MALT lymphoma. Lugano International Conference classification has been applied widely. Helicobacter pylori eradication is used as the first line treatment for gastric MALT lymphoma independent of the stage. The complete remission has been achieved in 60-90% of the stage I/II1 patients with Helicobacter pylori eradication only. The treatment options for the patients with refractory to eradication are radiotherapy, chemotherapy and/or immunotherapy with the complete remission rate of 75% to 100%. The incidence of gastric MALT lymphoma can be expected to down by virtue of the decrease of Helicobacter pylori infection rate. Further basic and clinical research is necessary to advance in determine the pathogenesis and management.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.465-482
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• 2021

Lipids, which along with carbohydrates and proteins are among the most important nutrients for the living organism, have a variety of biological functions that can be applied widely in biomedicine. A fatty acid, the most fundamental biological lipid, may be classified by length of its aliphatic chain, and the short-, medium-, and long-chain fatty acids and each have distinct biological activities with therapeutic relevance. For example, short-chain fatty acids have immune regulatory activities and could be useful against autoimmune disease; medium-chain fatty acids generate ketogenic metabolites and may be used to control seizure; and some metabolites oxidized from long-chain fatty acids could be used to treat metabolic disorders. Glycerolipids play important roles in pathological environments, such as those of cancers or metabolic disorders, and thus are regarded as a potential therapeutic target. Phospholipids represent the main building unit of the plasma membrane of cells, and play key roles in cellular signaling. Due to their physical properties, glycerophospholipids are frequently used as pharmaceutical ingredients, in addition to being potential novel drug targets for treating disease. Sphingolipids, which comprise another component of the plasma membrane, have their own distinct biological functions and have been investigated in nanotechnological applications such as drug delivery systems. Saccharolipids, which are derived from bacteria, have endotoxin effects that stimulate the immune system. Chemically modified saccharolipids might be useful for cancer immunotherapy or as vaccine adjuvants. This review will address the important biological function of several key lipids and offer critical insights into their potential therapeutic applications.