• Journal of Veterinary Clinics
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• v.18 no.1
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• pp.14-17
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• 2001

Recombinant interleukin-2 (IL-2) has demonstrated as an antineoplastic agent in mice and human, but the relatively low response rates observed in clinical trials. Therefore, the present study was undertaken in order to evaluate therapeutic activities of IL-2 for the establishment of therapeutic applications. At the onset of the experiment, normal C3H/HeN mice were injected with $3{\times}10^6$ RD-995 tumor cells, murine ultraviolet radiation-induced fibrosarcoma, subcutaneously. Beginning on day 25, experimental groups were treated with a 5-day course of IL-2 (subcutaneous injection of 30,000 IU every 12 hours for 5 days). The result of this experiment revealed that RD-995 tumor grew progressively in control mice. Subcutaneous IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 treated mice were observed compared with the control mice.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.5
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• pp.369-385
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• 2009

In this paper, the authors intended to summarize briefly the features of lymphoma with regard to $^{18}F$-FDG PET for assessment of tumor response to therapy, to describe why assessment of treatment response should be performed, to review what method so far has been used in monitoring treatment response, to discuss what limitations of morphologic imaging criteria for assessing tumor response are, in compared with $^{18}F$-FDG PET, and to introduce recently proposed criteria for assessing tumor response in malignant lymphoma. And also the authors emphasize the need to understand the characteristics of diagnostic performance of $^{18}F$-FDG PET in several clinical settings in order to interpret $^{18}F$-FDG PET results appropriately, and to encourage the use of interval likelihood ratio to enhance clinical implications of test results which, in turns, allows referring physicians to understand the meaning of interpretation with easy. Until recently, treatment response has been assessed according to the morphologic criteria. Metabolic imaging with $^{18}F$-FDG PET was adopted to have important role for treatment assessment in IWC+PET criteria proposed recently by IHP. To accomplish this role, we should perform and interpret $^{18}F$-FDG PET according to IWC+PET criteria. It is important for referring physicians to understand the various limitations of $^{18}F$-FDG PET and pitfalls in PET interpretation, and to understand that clinical information are needed by nuclear medicine physicians to optimize the interpretation of $^{18}F$-FDG PET.

• Archives of Pharmacal Research
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• v.22 no.4
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• pp.340-347
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• 1999

Dendritic cells (DCs) are potent professional antigen-presenting cells (APC) capable of inducing the primary T cell response to antigen. Although tumor cells express target antigens, they are incapable of stimulating a tumor-specific immune response due to a defect in the costimulatory signal that is required for optimal activation of T cells. In this work, we describe a new approach using tumor-DC coculture to improve the antigen presenting capacity of tumor cells which does not require a source of tumor-associated antigen. Immunization of a weakly immunogenic and progressive tumor cocultured with none marrow-derived DCs generated an effective tumor vaccine. Immunization with the cocutured DCs was able to induce complete protectiv immunity against tumor challenges and was effective for the induction of tumor-specific CTL (cytotoxic T lymphocyte) activity. Furthermore, high NK cell activity was observed in mice in which tumors were rejected. In addition, immunization with tumor-pulsed DC s induced delayed tumor growth, but not tumor eradication in tumor-bearing mice. Our results demonstrate that coculture of DCs with tumors generated antitumor immunity due to the NK cell activation as well as tumor-specific T cell. This approach would be used for designing tumor vaccines using DCs when the information about tumor antigens is limited.

• IMMUNE NETWORK
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• v.6 no.4
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• pp.185-191
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• 2006

Background: Based on outstanding progresses in animal experiments, vaccines for some human tumors have been developed. However, clinical effects of these vaccines have been far below than expected. This discrepancy might come from differences between animal models and human patients with respect to immunocompetency. The immune status of mice after tumor inoculation has not been well studied, which make us cautious in interpreting and applying the results from mice to human. We evaluated cell-mediated immune responses in mice after tumor cell inoculation. Methods: Mice were inoculated with TA3Ha, CT26, or 4T1. Delayed-type hypersensitivity (DTH) responses were induced 2-4 weeks after inoculation using 2,4-dinitro-1-fluorobenzene as an antigen. The relationships between the severity of DTH responses and the duration of tumor inoculation or the size of tumor mass were analyzed. Results: In T A3Ha groups, DTH response was elevated 2 weeks after inoculation, but depressed after 4 weeks, compared to the control group. When analyzed based on the sizes of tumor masses elicited, DTH responses were inversely related to the mass size, especially in those greater than 10 mm in diameter. In CT26 groups, while the duration after inoculation did not affect the severity of DTH responses, those with large mass showed depressed responses regardless the duration of inoculation. 4T1 cells grew so slowly that the size of tumor mass was small even 4 weeks after inoculation, and this group showed much higher DTH responses compared to that of tumor-free group. Conclusion: At least in an experimental setting where tumor model was induced by inoculating tumor cell lines into immunologically competent mice, the host immune response was elevated in early stage, and then depressed in late stage when the mass grew over a critical size.

• Radiation Oncology Journal
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• v.30 no.4
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• pp.218-225
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• 2012

Purpose: The relationship between treatment outcomes, alteration of the expression of biological markers, and tumor volume response during radiotherapy (RT) in patients with uterine cervical cancer was analyzed. Materials and Methods: Twenty patients with cervical squamous cell carcinoma received definitive RT with (n = 17) or without (n = 3) concurrent chemotherapy. Tumor volumes were measured by three serial magnetic resonance imaging scans at pre-, mid-, and post-RT. Two serial punch biopsies were performed at pre- and mid-RT, and immunohistochemical staining for cyclooxygenase (COX)-2 and epidermal growth factor receptor was performed. The median follow-up duration was 60 months. Results: The median tumor volume response at mid-RT (V2R) was 0.396 (range, 0.136 to 0.983). At mid-RT, an interval increase in the distribution of immunoreactivity for COX-2 was observed in 8 patients, and 6 of them showed poor mid-RT tumor volume response ($V2R{\geq}0.4$). Four (20%) patients experienced disease progression after 10 to 12 months (median, 11 months). All 4 patients had poor mid-RT tumor volume response (p = 0.0867) and 3 of them had an interval increase in COX-2 expression. Overall survival (OS) and progression-free survival (PFS) decreased in patients with $V2R{\geq}0.4$ (p = 0.0291 for both). An interval increase in COX-2 expression at mid-RT was also associated with a decreased survival (p = 0.1878 and 0.1845 for OS and PFS, respectively). Conclusion: Poor tumor volume response and an interval increase in COX-2 expression at mid-RT decreased survival outcomes in patients with uterine cervical cancer.

• IMMUNE NETWORK
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• v.4 no.1
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• pp.38-43
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• 2004

Backgroud: Immunotherapy using dendritic cells (DC) loaded with tumor antigens may represent a potentially effective method for inducing antitumor immunity. We evaluated the effectiveness of DC-based antitumor immune response in various conditions. Methods: DC were cultured from peripheral blood mononuclear cells (PBMNC) in myelogenous leukemia (ML) and lysates of autologous leukemic cells are used as tumor antigen. The effectiveness of interleukin-12 (IL-12) and CD40L (CD154) on the antigen presenting function of lysates-loaded DC was analyzed by proliferation, cytokine production, and cytotoxicity tests with activated PBMNC (mainly lymphocytes). For generating antigen-loaded DC, direct fusion of DC with ML was studied. Results: Antigen loaded DC induced significantly effective antitumor immune response against autologous leukemic cells. Administration of IL-12 on the DC based antitumor immune response showed higher proliferation activity, IFN-$\gamma$ production, and cytotoxic activity of PBMNC. Also, fused cell has a potent antitumor immune response. Conclusion: We conclude that lysates-loaded DC with IL-12 may be effectively utilized as inducer of antitumor immune reaction in ML and in vivo application with DC-based antitumor immunotherapy or tumor vaccination seems to be feasible.

• Journal of Environmental Health Sciences
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• v.19 no.3
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• pp.64-73
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• 1993

The study was conducted to investigate the mechanism of tumor promotion as the time courses and the doses of promoter, and the effect of plant fiavonoids on the TPA-induced ODC responses. The results are summarized as follows: 1. A single, toppical application of 17 nmole of the potent tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate, resulted in an induction of mouse epidermal Ornithine Decarboxylase with a peak at 5 hours after treatment and maximized 5.1 times as large as ODC activities of control. 2. Dose-response curve indicated that the tumor promotion increases proportionally between 1.7 and 170 nmole of TPA. This dose dependency relationship indicated that the ability of TPA to stimulate ODC is linked its ability to promote tumors. 3. Naturally occurring plant fiavonoids with anticarcinogenic and antipromotional activities were tested for their abilities to inhibit ODC response induced by skin tumor promoter TPA. Intra peritoneal administration of fiavonoids compounds (rutin, naphthofiavone, baicalein, quercitrin) and herbal drugs (sophorae rios, crataegi fructus, armeniacae semen) inhibited 17 nmole TPA-induced ODC activities in mouse epidermis in vivo.

• Radiation Oncology Journal
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• v.34 no.3
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• pp.230-238
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• 2016

Purpose: Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Materials and Methods: Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Results: Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. Conclusion: In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.

• Molecules and Cells
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• v.38 no.2
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• pp.112-121
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• 2015

Ectopic expression of $14-3-3{\zeta}$ has been found in various malignancies, including lung cancer, liver cancer, head and neck squamous cell carcinoma (HNSCC), and so on. However, the effect of $14-3-3{\zeta}$ in the regulation of interactions between tumor cells and the immune system has not been previously reported. In this study, we aimed to investigate whether and how $14-3-3{\zeta}$ is implicated in tumor inflammation modulation and immune recognition evasion. In oral squamous cell carcinoma (OSCC) cell lines and cancer tissues, we found that $14-3-3{\zeta}$ is overexpressed. In OSCC cells, $14-3-3{\zeta}$ knockdown resulted in the up-regulated expression of inflammatory cytokines. In contrast, $14-3-3{\zeta}$ introduction attenuated cytokine expression in human normal keratinocytes and fibroblasts stimulated with interferon-${\gamma}$ (IFN-${\gamma}$) and lipopolysaccharide (LPS). Furthermore, supernatants from $14-3-3{\zeta}$ knockdown OSCC cells dramatically altered the response of peritoneal macrophages, dendritic cells and tumor-specific T cells. Interestingly, Stat3 was found to directly interact with $14-3-3{\zeta}$ and its disruption relieved the inhibition induced by $14-3-3{\zeta}$ in tumor inflammation. Taken together, our studies provide evidence that $14-3-3{\zeta}$ may regulate tumor inflammation and immune response through Stat3 signaling in OSCC.

• BMB Reports
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• v.53 no.12
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• pp.628-633
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• 2020

WNT11 is a member of the non-canonical Wnt family and plays a crucial role in tumor progression. However, the regulatory mechanisms underlying WNT11 expression are unclear. Tumor necrosis factor-alpha (TNFα) is a major inflammatory cytokine produced in the tumor microenvironment and contributes to processes associated with tumor progression, such as tumor invasion and metastasis. By using site-directed mutagenesis and introducing a serial deletion in the 5'-regulatory region of WNT11, we observed that TNFα activates the early growth response 1 (EGR1)-binding sequence (EBS) in the proximal region of WNT11 and that the transcription factor EGR1 is necessary for the TNFα-induced transcription of WNT11. EGR1 bound directly to the EBSs within the proximal 5'-regulatory region of WNT11 and ectopic expression of EGR1 stimulated WNT11 promoter activity, whereas the knockdown of EGR1 expression by RNA interference reduced TNFα-induced WNT11 expression in T47D breast cancer cells. We also observed that mitogen-activated protein kinases (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase mediated TNFα-induced transcription of WNT11 via EGR1. Our results suggest that EGR1 directly targets WNT11 in response to TNFα stimulation in breast cancer cells.