• IMMUNE NETWORK
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• v.11 no.4
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• pp.210-215
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• 2011

It is already known that high concentration of vitamin C induces apoptosis on tumor cells. However, there is no report regarding the function of vitamin C on the modulation of immune susceptibility of cancer. Therefore, we investigated whether vitamin C can modulate immune susceptibility of tumor cells, especially on the induction of Fas-mediated apoptosis. First, the optimal concentration of vitamin C, which cannot induce damages on tumor cells for 36 hrs. We found that 2 mM of vitamin C did not show harmful effect. In addition, the optimal concentration of agonistic anti-Fas Abs for 18 hrs was examined. As a result, 400 ng/ml of agonistic anti-Fas Abs did not induce apoptosis on tumor cells. Next, we tried to find the effect of 2 mM of vitamin C on the modulation of the susceptibility to agonistic anti-Fas Abs. When tumor cells were cultured with 400 ng/ml of agonistic anti-Fas Abs for 18 hrs, after pre-treatment with 2 mM of vitamin C for 24 hrs, viability of cells was decreased. Interestingly, we found that the expression of Fas (CD95) and MHC class I was increased by the treatment of vitamin C. Taken together, vitamin C increases the susceptibility of tumor cells to anti-Fas Abs and the expression of Fas (CD95) and MHC class I on tumor cells.

• Journal of Microbiology and Biotechnology
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• v.25 no.7
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• pp.1036-1046
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• 2015

Extracts from Asian medicinal herbs are known to be successful therapeutic agents against cancer. In this study, the effects of three types of herbal extracts on anti-tumor growth were examined. Among the three types of herbal extracts, H9 showed stronger anti-tumor growth effects than H5 and H11 in vivo. To find the molecular mechanism by which H9 inhibited the proliferation of breast cancer cell lines, the levels of apoptotic markers were examined. Proapoptotic markers, including cleaved PARP and cleaved caspases 3 and 9, were increased, whereas the anti-apoptotic marker Bcl-2 was decreased by H9 treatment. Next, the combined effect of H9 with the chemotherapeutic drugs doxorubicin/cyclophosphamide (AC) on tumor growth was examined using 4T1-tumor-bearing mice. The combined treatment of H9 with AC did not show additive or synergetic anti-tumor growth effects. However, when tumor-bearing mice were co-treated with H9 and the targeted anti-tumor drug trastuzumab, a delay in tumor growth was observed. The combined treatment of H9 and trastuzumab caused an increase of natural killer (NK) cells and a decrease of myeloid-derived suppressor cells (MDSC). Taken together, H9 induces the apoptotic death of tumor cells while increasing anti-tumor immune activity through the enhancement of NK activity and diminishment of MDSC.

• BMB Reports
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• v.53 no.10
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• pp.512-520
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• 2020

T-cell-based cancer immunotherapies, such as immune checkpoint blockers (ICBs) and chimeric antigen receptor (CAR)-T-cells, have significant anti-tumor effects against certain types of cancer, providing a new paradigm for cancer treatment. However, the activity of tumor infiltrating T-cells (TILs) can be effectively neutralized in the tumor microenvironment (TME) of most solid tumors, rich in various immunosuppressive factors and cells. Therefore, to improve the clinical outcomes of established T-cell-based immunotherapy, adjuvants that can comprehensively relieve multiple immunosuppressive mechanisms of TME are needed. In this regard, recent studies have revealed that metformin has several beneficial effects on anti-tumor immunity. In this mini-review, we understand the immunosuppressive properties of TME and how metformin comprehensively enhances anti-tumor immunity. Finally, we will discuss this old friend's potential as an adjuvant for cancer immunotherapy.

• Korean Journal of Veterinary Research
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• v.37 no.4
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• pp.843-854
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• 1997

Sixteen mammary gland tumors were collected from Seoul National University and Kangwon National University. The average age of the bitches with mammary gland tumor was 10 years. Total 17(60.7%) out of 28 tumor masses observed in 4th and 5th glands. Classification of these tumors according to Hampe and Misdorp were simple adenoma, complex adenoma, benign mixed tumor, papillary adenocarcinoma, solid adenocarcinoma and malignant mixed tumor. Immunohistochemical reaction of the intermediate filaments against normal canine mammary gland showed as followed; anti-cytokeratin 18 was strong and anti-cytokeratin 14 was moderate to the luminal epithelium. Anti-cytokeratin 14 and anti-pancytokeratin to the myoepithelium were showed strong, but anti-vimentin was weak in reactivity. Anti-vimentin to the interstitial cells was represented strong reactivity. The origin of cartilage in mixed tumor of canine mammary gland was studied immunohistochemically with antibodies against intermediate filament. In mammary gland mixed tumors, cartilage tumor tissues were surrounded with the irregularly demarcated three zones composed of adjacent star shaped cells in myxoid areas, proliferative spindle shaped cells and basal located proliferated cells. From basal proliferated cells to star shaped cells, the immunohistochemical reactivity of myoepithelium specific anti-pancytokeratin was decreased gradually and the reactivity of interstitial cell specific anti-vimentin was increased gradually. Based on these immunohistochemical staining patterns, we suggested that the origin of cartilagenous components in canine mammary gland mixed tumor is most likely to the proliferation and metaplsia of myoepithelium.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.9 no.1
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• pp.53-63
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• 2003

This study was analyzed the effects of blood-activating and stasis-eliminating herbs on anti-tumor and hematogenic metastasis. The metastasis and recurrence of tumor was the basis of yudok(yudu) on remained tumor cell and stagnation of blood, thermotoxo, phlegm, asthenia of healthy enerngy, stagnation of vital energy. Malignant tumor is caused by carcinogen and go through the progress of initiation, promotion, progression, it is closely related with Eohyul$(y{\grave{u}}xi {\breve{e}})$. Symptoms of blood stasis disease are purplish tongue, mass, fixed stabbing pain, ecchymosis of nail, hypodermic petechia, dermal thesaurismosis, melena, ecchymoma, disturbance of circulation. Effects on the therapy of activating blood circulation and congestion are anti-tumor, anti-coagulation, anti-hemolysis, anti-solution, anti-inflammation, anti-infection, control of blood circulations, control of connective tissue metabolism and control of immunity. They can directly kill the cancer cells entering the blood circulation, inhibit the formation of tumor embody and reduce the blood hyperviscosity. It is suggested that these herbs can be used to prevent and treat blood metastasis of cancer under the guidance of syndrome differentiation.

• Animal cells and systems
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• v.12 no.4
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• pp.193-201
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• 2008

The eventual goal of tumor immunotherapy is to develop a vaccine inducing a specific anti-tumor immunity. Cytokine gene therapy is an effective way at least in animal models, but limited efficacy and various side effects obstruct clinical applications. In this study, we developed a tumor vaccine expressing a membrane-bound form of IL-2(mbIL-2) and SDF-1 in B16F10 melanoma cells. The tumor clones expressing mbIL-2 showed reduced tumorigenicity, and additional expression of SDF-1 to mbIL-2 expressing tumor cells caused more severe reduction in tumorigenicity. However, expression of the SDF-1 alone did not affect on the tumorigenicity, probably because of limited production of SDF-1 in the SDF-1 transfected clones. When the mice once rejected mbIL-2/SDF-1 expressing tumor clone were re-challenged with wild type B16F10 tumor cells, all of the mice survived. This result suggests that mbIL-2/SDF-1 tumor clone is effective in inducing systemic anti-tumor immunity against wild type B16 melanoma. Furthermore, culture supernatant of tumor clones expressing SDF-1 induced lymphocyte migration in vitro. These results, all together, suggest that expression of mbIL-2 and SDF-1 in tumor cells enhances anti-tumor immune responses through different roles; the secreted SDF-1 may function as a chemoattractant to recruit immune cells to tumor vaccine injection site, and the mbIL-2 on tumor cells may provide costimulatory signal for CTL activation in physical contacts.

• Journal of Pharmacopuncture
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• v.4 no.3
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• pp.23-37
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• 2001

Objective: The purpose of this study is to develop and activate anti-tumor herbal acupuncture for cancer patients in South Korea. Methods: We investigated some literatures on anti-tumor herbal acupuncture which is used in South Korea and China, and made diagrams. Results: The results are summarized as follows. Anti-tumor herbal acupuncture is one of the traditional oriental medical method which is effective for cancer patients. In domestic studies, most of herb materials are belong to action of cooling&detoxification(25.0%) and strengthening body resistance(46.4%) which are proved to have effects of anti-tumor, immune activation and preventing tumor. In China, point injection therapy are used for improving symptoms of cancer patients and hea1ing tumor. Also herbal intravenous injection is used for combination of chinese traditional and western cancer therapy and treating cancer patients variously. Conclusions: From the above results. it is expected that anti-tumor herbal acupuncture is useful to improve clinical symptoms and quality of life(QOL) of cancer patients. Also we must develop new progressive methods of point injection and herbal intravenous injection for treating cancer patients, and advance clinical studies and trials.

• IMMUNE NETWORK
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• v.12 no.6
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• pp.269-276
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• 2012

The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either $CD34^+$ hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-${\beta}$ secretion were higher in SDC but CCR7 expression, IFN-${\gamma}$ and IL-10 secretion were higher in MoDC. The proportion of $CD11c^+CD8a^+$ cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-${\gamma}$ secreting $CD8^+$ T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer.

• BMB Reports
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• v.43 no.12
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• pp.773-780
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• 2010

Cancers are still difficult targets despite recent advances in cancer therapy. Due to the heterogeneity of cancer, a single-treatment modality is insufficient for the complete elimination of cancer cells. Therapeutic strategies from various aspects are needed. Gene therapy has been expected to bring a breakthrough to cancer therapy, but it has not yet been successful. Gene therapy also should be combined with other treatments to enhance multiple therapeutic pathways. In this view, gene delivery vector itself should be equipped with intrinsic anti-cancer activities. HVJ (hemagglutinating virus of Japan; Sendai virus) envelope vector (HVJ-E) was developed to deliver therapeutic molecules. HVJ-E itself possessed anti-tumor activities such as the generation of anti-tumor immunities and the induction of cancer-selective apoptosis. In addition to the intrinsic anti-tumor activities, therapeutic molecules incorporated into HVJ-E enabled to achieve multi-modal therapeutic strategies in cancer treatment. Tumor-targeting HVJ-E was also developed. Thus, HVJ-E will be a novel promising tool for cancer treatment.

• Gut and Liver
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• v.12 no.6
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• pp.623-632
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• 2018

Intestinal Behçet's disease is a rare, immune-mediated chronic intestinal inflammatory disease; therefore, clinical trials to optimize the management and treatment of patients are scarce. Moreover, intestinal Behçet's disease is difficult to treat and often requires surgery because of the failure of conventional medical treatment. Administration of anti-tumor necrosis factor-${\alpha}$, a potential therapeutic strategy, is currently under active clinical investigation, and evidence of its effectiveness for both intestinal Behçet's disease and inflammatory bowel diseases has been accumulating. Here, we review updated data on current experiences and outcomes after the administration of anti-tumor necrosis factor-${\alpha}$ for the treatment of intestinal Behçet's disease. In addition to infliximab and adalimumab, which are the most commonly used agents, we describe agents such as golimumab, etanercept, and certolizumab pegol, which have recently been shown to be effective in refractory intestinal Behçet's disease. This review also discusses safety issues associated with anti-tumor necrosis factor-${\alpha}$, including vulnerability to infections and malignancy.