• Journal of Microbiology and Biotechnology
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• v.10 no.3
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• pp.399-404
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• 2000

The adjuvant effect of a muramyl dipeptide (MDP) derivative, MDP-Lys(L18), on enhancing of antitumor immunity induced by X-irradiated tumor cells against highly metastatic B16-BL6 melanoma cells was examined in mice. Mice immunized intradermally (i.d.) with a mixture of X-irradiated B16-BL6 cells and MDP-Lys (L18) [Vac+MDP-Lys (L18)] followed by an intravenous (i.v.)inoculation of $10^4$ viable tumor cells 7 days after immunization, showed a significant inhibition of experimental lung metastasis of B16-BL6 melanoma cells. The most effective immunization for the prophylactic inhibition of tumor metastasis was obtained from the mixture of $100{\;}\mu\textrm{g}$ of MDP-Lys (L18) and $10^4$ X-irradiatied tumor vaccine. Furthermore, immunization of mice with Vac+MDP-Lys(L18), 3 days after tumor challenge, resulted in a significant inhibition of lung metastasis of B16-BL6 melanoma cells in an experimental lung metastasis model. Similarly, the administration of Vac+MDP-Lys(L18), 1 or 7 days after tumor removal, markedly inhibited tumor metastasis of B16-BL6 in a spontaneous lung metastasis model. When Vac+MDP-Lys (L18) was i.d. administered 3 days after subcutaneous (s.c.) inoculation of tumor cells ($5{\times}10^5/site$) on the back, mice treated with Vac+MDP-Lys(L18) showed inhibition of significantly tumor growth on day 20. These results suggest that MDP-Lys (L18) is able to enhance antitumor activity induced by X-irradiated tumor vaccine to reduce lung metastasis of tumor cells, and is a potent immunomodulating agent which may be applied prophylactically as well as therapeutically to treatment of cancer metastasis.

• Journal of radiological science and technology
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• v.31 no.4
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• pp.355-365
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• 2008

Purpose : This study isto determine the grade of brain tumor and compare the characteristics in each grade using in MRS (MR Spectroscopy). Method : STEAM (Stimulated Echo Acquisition Method) and protocol of PRESS (Point Resolved Spectroscopy) were used in the levels of tumor grade. We classified the pattern of tumor and analysis of the spectrum signals quantitatively from voxel in the brain tumor grade. In accordance with the result, we calculated the accuracy of biochemical. Result : In high-grade tumor, the NAA/Cr showed the signal reduction of 29.4% and 53.9%. However Cho/Cr increased 570% and 711%. However, in low-grade tumor, NAA/Cr downed to 42.6% and 58.1%. Cho/Cr increased to 188% and 195%. Conclusion : The study suggests that the comparative analysis of signals from MR spectroscopy could be useful to evaluate the grade of tumor and find out the characteristics of it. By extension, MR spectroscopy can be used for research with other organs in the human.

• Radiation Oncology Journal
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• v.30 no.2
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• pp.70-77
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• 2012

Purpose: To evaluate the patterns of tumor shape and to compare tumor volume derived from simple diameter-based ellipsoid measurement with that derived from tracing the entire tumor contour using region of interest (ROI)-based 3D volumetry with respect to the prediction outcome in cervical cancer patients treated with concurrent chemotherapy and radiotherapy. Materials and Methods: Magnetic resonance imaging was performed in 98 patients with cervical cancer (stage IB-IIIB). The tumor shape was classified into two categories: ellipsoid and non-ellipsoid shape. ROI-based volumetry was derived from each magnetic resonance slice on the work station. For the diameter-based surrogate "ellipsoid volume," the three orthogonal diameters were measured to calculate volume as an ellipsoid. Results: The more than half of tumor (55.1%) had a non-ellipsoid configuration. The predictions for outcome were consistent between two volume groups, with overall survival of 93.6% and 87.7% for small tumor (<20 mL), 62.9% and 69.1% for intermediate-size tumor (20-39 mL), and 14.5% and 16.7% for large tumors (${\geq}$40 mL) using ROI and diameter based measurement, respectively. Disease-free survival was 93.8% and 90.6% for small tumor, 54.3% and 62.7% for intermediate-size tumor, and 13.7% and 10.3% for large tumor using ROI and diameter based method, respectively. Differences in outcome between size groups were statistically significant, and the differences in outcome predicted by the tumor volume by two different methods. Conclusion: Our data suggested that large numbers of cervical cancers are not ellipsoid. However, simple diameter-based tumor volume measurement appears to be useful in comparison with ROI-based volumetry for predicting outcome in cervical cancer patients.

• International Journal of Vascular Biomedical Engineering
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• v.2 no.1
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• pp.17-24
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• 2004

Tumor angiogenesis was simulated using a two-dimensional computational model. The equation that governed angiogenesis comprised a tumor angiogenesis factor (TAF) conservation equation in time and space, which was solved numerically using the Galerkin finite element method. The time derivative in the equation was approximated by a forward Euler scheme. A stochastic process model was used to simulate vessel formation and vessel elongation towards a paracrine site, i.e., tumor-secreted basic fibroblast growth factor (bFGF). In this study, we assumed a two-dimensional model that represented a thin (1.0 mm) slice of the tumor. The growth of the tumor over time was modeled according to the dynamic value of bFGF secreted within the tumor. The data used for the model were based on a previously reported model of a brain tumor in which four distinct stages (namely multicellular spherical, first detectable lesion, diagnosis, and death of the virtual patient) were modeled. In our study, computation was not continued beyond the 'diagnosis' time point to avoid the computational complexity of analyzing numerous vascular branches. The numerical solutions revealed that no bFGF remained within the region in which vessels developed, owing to the uptake of bFGF by endothelial cells. Consequently, a sharp, declining gradient of bFGF existed near the surface of the tumor. The vascular architecture developed numerous branches close to the tumor surface (the brush-border effect). Asymmetrical tumor growth was associated with a greater degree of branching at the tumor surface.

• Journal of Korean Neurosurgical Society
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• v.30 no.12
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• pp.1381-1387
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• 2001

Objective : Endodermal sinus tumor or yolk sac tumor is an uncommon malignant germ-cell neoplasm. This tumor was originally described as a germ cell tumor of the ovary or the testis. Intracranial endodermal sinus tumor is extremely rare and usually develop in the pineal or suprasellar regions. The authors evaluated the effect of adjuvant therapy(chemotherapy combined with radiotherapy) and radical removal of intracranial endodermal sinus tumors. Material and Methods : Between 1996 and 2001, four patients of intracranial endodermal sinus tumor were diagnosed with tumor marker(AFP) and biopsy. Three patients were treated with surgical removal and chemotherapy with cisplatin($20mg/m^2$), etoposide($100mg/m^2$) and bleomycin($15mg/m^2$) as well as external beam radiation therapy. We compared the management problems for these tumors. Result : In all three patients the tumor size and the level of tumor marker decresed during initial adjuvant therapy. However, Tumors showed regrowth with elevated AFP of serum and CSF possibly related to delayed chemotherapeutic treatment or inadequate administration of chemotherapeutic drugs due to severe bone marrow suppression. An additional chemotherapy and external radiation therapy were given, but tumors could not be controlled with leptomeningeal seeding. Conclusion : Radiotherapy is considered to be less effective. The combination chemotherapy with PVB(cisplatin, vinblastine, bleomycine) or PE(cisplatin, etoposide) is considered to be value in prolongation of the survival rate. But the role of chemotherapy in this tumor has not yet been clarified due to bone marrow suppression and drug resistance. Further study with large series of this tumor is necessary to establish the optimal management.

• 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.

• The Journal of the Korean bone and joint tumor society
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• v.13 no.2
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• pp.173-179
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• 2007

Brown tumor is tumor like lesion resulted from hyperparathyroidism, and it has been rarely reported recently. We evaluated a 29-year-old woman who had brown tumor on proximal humerus caused by primary hyperparathyroidism. She first had presented pain and swelling over the upper arm, and was suspected as giant cell tumor in biopsy combined with hyperparathyroidism. Wide marginal excision and tumor prosthesis were performed. However, it was confirmed as brown tumor resulted from parathyroid adenoma according to laboratory findings and radioactive isotopes image, and surgical excision of adenoma relieved clinical symptoms. We report this case with a review of literatures.

• IMMUNE NETWORK
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• v.21 no.6
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• pp.44.1-44.15
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• 2021

Tumor peptides associated with MHC class I molecules or their synthetic variants have attracted great attention for their potential use as vaccines to induce tumor-specific CTLs. However, the outcome of clinical trials of peptide-based tumor vaccines has been disappointing. There are various reasons for this lack of success, such as difficulties in delivering the peptides specifically to professional Ag-presenting cells, short peptide half-life in vivo, and limited peptide immunogenicity. We report here a novel peptide vaccination strategy that efficiently induces peptide-specific CTLs. Nanoparticles (NPs) were fabricated from a biodegradable polymer, poly(D,L-lactic-co-glycolic acid), attached to H-2K^b molecules, and then the natural peptide epitopes associated with the H-2K^b molecules were exchanged with a model tumor peptide, SIINFEKL (OVA_257-268). These NPs were efficiently phagocytosed by immature dendritic cells (DCs), inducing DC maturation and activation. In addition, the DCs that phagocytosed SIINFEKL-pulsed NPs potently activated SIINFEKL-H2K^b complex-specific CD8⁺ T cells via cross-presentation of SIINFEKL. In vivo studies showed that intravenous administration of SIINFEKL-pulsed NPs effectively generated SIINFEKL-specific CD8⁺ T cells in both normal and tumor-bearing mice. Furthermore, intravenous administration of SIINFEKL-pulsed NPs into EG7.OVA tumor-bearing mice almost completely inhibited the tumor growth. These results demonstrate that vaccination with polymeric NPs coated with tumor peptide-MHC-I complexes is a novel strategy for efficient induction of tumor-specific CTLs.

• IMMUNE NETWORK
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• v.21 no.3
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• pp.23.1-23.16
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• 2021

Chemokines are key factors that influence the migration and maintenance of relevant immune cells into an infected tissue or a tumor microenvironment. Therefore, it is believed that the controlled administration of chemokines in the tumor microenvironment may be an effective immunotherapy against cancer. Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Here, we investigated the role of CCL3 in regulating the tumor microenvironment using a syngeneic mouse tumor model. We observed that MC38 tumors overexpressing CCL3 (CCL3-OE) showed rapid regression compared with the wild type MC38 tumors. Additionally, these CCL3-OE tumors showed an increase in the proliferative and functional tumor-infiltrating T cells. Furthermore, PD-1 immune checkpoint blockade accelerated tumor regression in the CCL3-OE tumor microenvironment. Next, we generated a modified CCL3 protein for pre-clinical use by fusing recombinant CCL3 (rCCL3) with a non-cytolytic hybrid Fc (HyFc). Administering a controlled dose of rCCL3-HyFc via subcutaneous injections near tumors was effective in tumor regression and improved survival along with activated myeloid cells and augmented T cell responses. Furthermore, combination therapy of rCCL3-HyFc with PD-1 blockade exhibited prominent effect to tumor regression. Collectively, our findings demonstrate that appropriate concentrations of CCL3 in the tumor microenvironment would be an effective adjuvant to promote anti-tumor immune responses, and suggest that administering a long-lasting form of CCL3 in combination with PD-1 blockers can have clinical applications in cancer immunotherapy.

• 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.