• IMMUNE NETWORK
• /
• v.16 no.2
• /
• pp.134-139
• /
• 2016

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.

• BMB Reports
• /
• v.43 no.12
• /
• pp.773-780
• /
• 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
• /
• v.12 no.6
• /
• pp.623-632
• /
• 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.

• Archives of Pharmacal Research
• /
• v.26 no.9
• /
• pp.727-730
• /
• 2003

The in vivo anti-tumor activities of decursinol angelate (1) and decursin (2) isolated from the roots of Angelica gigas were investigated. These two compounds, when administered consecutively for 9 days at 50 and 100 mg/kg i.p. in mice, caused a significant increase in the life span and a significant decrease in the tumor weight and volume of mice inoculated with Sarcoma-180 tumor cells. These results suggest that decursinol angelate (1) and decursin (2) from A. gigas have anti-tumor activities.

• BMB Reports
• /
• v.56 no.3
• /
• pp.140-144
• /
• 2023

While CD8⁺ cytotoxic T cells have long been considered the primary effector in controlling tumors, the involvement of CD4⁺ "helper" T cells in anti-tumor immunity has been underappreciated. The investigations of intra-tumoral T cells, fueled by the recent advances in genomic technologies, have led to a rethinking of the indirect role of CD4⁺ T cells that have traditionally been described as a "helper". Accumulating evidence from preclinical and clinical studies indicates that CD4⁺ T cells can acquire intrinsic cytotoxic properties and directly kill various types of tumor cells in a major histocompatibility complex class II (MHC-II)-dependent manner, as opposed to the indirect "helper" function, thus underscoring a potentially critical contribution of CD4⁺ cytotoxic T cells to immune responses against a wide range of tumor types. Here, we discuss the biological properties of anti-tumor CD4⁺ T cells with cytotoxic capability and highlight the emerging observations suggesting their more significant role in anti-tumor immunity than previously appreciated.

• The Journal of Internal Korean Medicine
• /
• v.25 no.4
• /
• pp.242-251
• /
• 2004

In this piece of research, Prunellae spica is added to Sambonggangyongbaneotang for one group and Trionycis carapax is added to Sambonggangyongbaneotang for the other group. With these two different prescriptions, the degrees of tumor suppression are compared to develop a better prescription. SKH = Sambonggangyongbaneo-tang + Prunellae Spica SKB = Sambonggangyongbaneo-tang + Trionycis Carapax The results were as follows: 1. SKH and SKB demonstrated anti-tumor effects against tumor advancement of S-180 2. SKH and SKB showed on elevation of macrophage for tumor-bearing mice. 3. $100{\mu}g/ml,\;500{\mu}g/ml$ of SKH and $500{\mu}g/ml$ of SKB demonstrated a rise in alkaline phosphates of B-Lymphocyte in the spleen in tumor-bearing mice. Results support a role for both SKH and SKB for anti-tumor effects via endorsement of macrophage and encouragement of B-lymphocyte toward S-180.

• Korean Journal of Pharmacognosy
• /
• v.43 no.1
• /
• pp.32-38
• /
• 2012

To examine the potentiation of Macrolepiota procera extracts (MPE-4) to act as adjuvant enhancing the tumor specific anti-tumor immune response, tumor vaccine prepared by boiling (HK vaccine) admixed with MPE-4 and immunized in mice. Vaccination of mice with HK vaccine in combination with MPE-4 resulted in higher inhibition in tumor metastasis compared with the mice of HK vaccine alone treatment against live syngeneic tumor cell challenge. The splenocytes from mice immunized HK vaccine mixed with MPE-4 was able to elicit a stronger cytotoxic T lymphocyte (CTL) response as compared with HK vaccine alone. In addition, the splenocytes from MPE-4 admixed HK vaccine immunized mice secreted a higher concentration of Th1 type cytokine such as IFN-${\gamma}$, and GM-CSF. Furthermore, the adoptive transfer of splenocytes from mice immunized HK vaccine and MPE-4 led to a more robust anti-tumour response than the HK vaccine alone. Overall, these results indicate that MPE-4 is a good candidate adjuvant of anti-tumor immune response.

• Journal of the East Asian Society of Dietary Life
• /
• v.12 no.4
• /
• pp.289-298
• /
• 2002

This study was designed to investigate the anti-tumor effects of fresh carrot juice, methanol-extracts, and $\beta$-carotene on the human lung cancer cell line NCI-H1299. The anti-tumor effect was evaluated by the MTT assay in vitro. The anti-tumor effect of fresh carrot juice against NCI-H1299 lasted up to 96 hours after exposure; the viability rate of lung cancer cells decreased below 50% after 48 hours, and further after 72 hours. The strongest propagation inhibition effect of fresh carrot juice was shown at the concentration of 2000 $\mu\textrm{g}$/$m\ell$ after 72 hours and the viability rates was 45.98% even at the concentration of 25 $\mu\textrm{g}$/$m\ell$. The value of $IC_{50}$/ was 23.1$\mu\textrm{g}$/$m\ell$ when the elapsed time was 72 hours. The viability rate of methanol-extract was 52.4% under the concentration of 2000 $\mu\textrm{g}$/$m\ell$ and the elapsed time of 72 hours. Under the concentration of 1000 $\mu\textrm{g}$/$m\ell$ and the elapsed time of 48 hours, $\beta$ -carotene decreased the viability rate to 29.99%. The $IC_{50}$/ value of $\beta$-carotene was 691.2$\mu\textrm{g}$/$m\ell$ after 72 hours. According to the above results, the anti-tumor effect arose in NCI-H1299 when the concentration of the fresh carrot juice or the $\beta$-carotene was more than 25 $\mu\textrm{g}$/$m\ell$ or 1000 $\mu\textrm{g}$/$m\ell$, respectively. On the other hand, the methanol-extracts showed a weak anti-tumor effect even at a concentration as high as 2000 $\mu\textrm{g}$/$m\ell$.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.22 no.1
• /
• pp.31-40
• /
• 2009

Purpose: This study was carried out to investigate the anti-tumor metastasis effect and activation of innate immunity by extracts of Mori radicis cortex. Methods: Anti-tumor metastatic experiment was conducted in vitro and in vivo by using colon 26-M3.1 carcinoma cell, L5178Y-R lymphoma cell and HeLa cell. To observe the activation of innate immunity by extracts of Mori radicis cortex, we estimated IL-6, IL-10, IL-12, TNF-${\alpha}$ from peritoneal macrophages. And we evaluated the activation of NK cell by using anti-asialo-GM1 serum. Results: We found that the administration of Mori radicis cortex extracts significantly inhibited tumor metastasis. In an in vitro cytotoxicity analysis, Mori radicis cortex affected tumor cell growth above specific concentration. Mori radicis cortex also stimulated peritoneal macrophage, which was followed by the production of various cytokines such as IL-6, IL-10, IL-12, TNF-${\alpha}$. The depletion of NK cells by anti-asialo GM1 serum partly abolished the inhibitory effect of Mori radicis cortex on tumor metastasis. Conclusion: Mori radicis cortex appears to have considerable activity on the anti-metastasis by activation of innate immunity.

• Biomolecules & Therapeutics
• /
• v.13 no.2
• /
• pp.113-117
• /
• 2005

Organosulfur compounds have been shown to exert an anti-cancer activity. In an attempt to develop novel chemopreventive and anti-cancer agents for liver cancer, we synthesized allylthiopyridazine derivatives. We have previously shown that allylthiopyridazine derivatives exert inhibitory effects on proliferation, invasion and migration of SK-Hep-1 hepatocarcinoma cells in vitro. The in vivo anti-tumor effect of 3-methvl-6-allylthiopy-ridazine, named as K6, was also reported. In this study, we further investigated the preclinical anti-cancer efficacy of K6 for hepatocarcinoma using nude mice xenografted with Hep-G2 hepatocellular carcinoma cells. K6(20-100 mg/kg, orally administered everyday for 30 days) markedly decreased the tumor volume of Hep-G2 cell-transplanted nude mice as evidenced by ultrasonographic and plethysmogranhic analyses. The inhibitory effect on tumor volume was lower than that exerted by doxorubicin (2 mg/kg), intravenously injected) which was used as a positive control. This study shows that K6 efficiently suppresses xenograft tumor growth, revealing K6 as apotential anti-cancer agent for suppressing in vivo progression of liver cancer. Given that hepatocarcinoma is among the most prevalent and lethal malignancies and there is no effective treatment to date, our study may contribute to the potential drug development for liver cancer.