• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.2
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• pp.81-93
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• 2007

Purpose: Adenoid cystic carcinoma (ACC) is a relatively rare tumor that arises in glandular tissues of the head and neck region and sometimes has a protracted clinical course with perineural invasion and delayed onset of distant lung metastasis. Treatment failure of salivary ACC is most often associated with perineural and hematogenous tumor spread. However, very little has been known about the cellular and molecular mechanisms of perineural invasion and hematogenous distant metastasis of parotid ACC. This study was designed to develop an orthotopic tumor model of parotid adenoid cystic carcinoma in athymic nude mice. Experimental Design: A melanoma cell line was injected into the parotid gland of athymic mice to determine whether such implantation was technically feasible. A parotid ACC cell line was then injected into the parotid gland or the subcutaneous tissue of athymic mice at various concentrations of tumor cells, and the mice were thereafter followed for development of tumor nodule. The tumors were examined histopathologically for perineural invasion or regional or distant lung metastasis. We used an oral squmous cell carcinoma cell line as control. Results: Implantation of tumor(melanoma) cell suspension into the parotid gland of nude mice was technically feasible and resulted in the formation of parotid tumors. A parotid ACC cell line, ACC3 showed no significantly higher tumorigenicity, but showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. In contrast, mucosal squmous cell carcinoma cell line doesn’t show significantly higher lung metastatic potential in the parotid gland than in the subcutis. The ACC tumor established in the parotid gland seemed to demonstrate perineural invasion of facial nerve, needs further study. Conclusion: An orthotopic tumor model of salivary ACC in athymic nude mice was successfully developed that closely recapitulates the clinical situations of human salivary ACC. This model should facilitate the understanding of the cellular and molecular mechanisms of tumorigenisis and metastasis of salivary ACC and aid in the development of targeted molecular therapies of salivary ACC.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.383-389
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• 2011

Background: EY-6 is one of the newly synthesized indoledione derivatives to induce tumor cell-specific cell death. In this study, we investigated the mechanism of immunological death induced by EY-6 at mouse colon cancer cell as well as at the normal immune cell represented by dendritic cell. Methods: C57BL/6 mouse syngeneic colon cancer cell MC38 was treated with EY-6, and analyzed by MTT for viability test, flow cytometry for confirming surface expressing molecules and ELISA for detection of cytokine secretion. Normal myeloid-dendritic cell (DC) was ex vivo cultured from bone marrow hematopoietic stem cells of C57BL/6 mice with GM-CSF and IL-4 to analyze the DC uptake of dead tumor cells and to observe the effect of EY-6 on the normal DC. Results: EY-6 killed the MC38 tumor cells in a dose dependent manner (25, 50 and $100{\mu}M$) with carleticulin induction. And EY-6 induced the secretion of IFN-${\gamma}$ but not of TNF-${\alpha}$ from the MC38 tumor cells. EY-6 did not kill the ex-vivo cultured DCs at the dose killing tumor cells and did slightly but not significantly induced the DC maturation. The OVA-specific cross-presentation ability of DC was not induced by chemical treatment (both MHC II and MHC I-restricted antigen presentation). Conclusion: Data indicate that the EY-6 induced tumor cell specific and immunological cell death by modulation of tumor cell phenotype and cytokine secretion favoring induction of specific immunity eliminating tumor cells.

• IMMUNE NETWORK
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• v.5 no.3
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• pp.163-171
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• 2005

Background: To perform the successful dendritic cell-based cancer immunotherapy one of the main issues to be solved is the source of antigen for DC pulsing. Limitations occur by using auto-tumor lysate due to the difficulties obtaining enough tumor tissue(s) quantitatively as well as qualitatively. In this study the possibility of allogeneic tumor cell lysate as a DC pulsing antigen has been tested in mouse melanoma pulmonary me tastasis model. Methods: B16F10 melanoma cells $(1{\timeS}10^5/mouse)$ were inoculated intra venously into the C57BL/6 mouse. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 (1,000 U/ml each) for 7 days and pulsed with lysate of either autologous B16F10 (B-DC), allogeneic K1735 (C3H/He origin; K-DC) or CloneM3 (DBA2 origin; C-DC) melanoma cells for 18 hrs. Pulsed-DCs $(1{\times}10^6/mouse)_{[CGP1]}$ were injected i.p. twice with one week interval starting from the day 1 after tumor cell inoculation. Results: Without observable toxicity, allogeneic tumor cell lysate pulsed-DC induced the significantly better anti-tumor response (tumor scale: $2.7{\pm}0.3,\;0.7{\pm}0.3\;and\;0.3{\pm}0.2$ for saline, B-DC and C-DC treated group, respectively). Along with increased tumor specific lymphocyte proliferations, induction of IFN-${\gamma}$ secretion against both auto- and allo-tumor cell lysates was observed from the DC treated mice. (w/B16F10-lysate: $44.97{\pm}10.31,\;1787.94{\pm}131.18,\;1257.15{\pm}48.27$, w/CloneM3 lysate: 0, $1591.13{\pm}1.83,\;1460.47{\pm}86.05pg/ml$ for saline, B-DC and C-DC treated group, respectively) Natural killer cell activity was also increased in the mice treated with tumor cell lysate pulsed-DC ($8.9{\pm}_{[CGP2]}0.1,\;11.6{\pm}0.8\;and\;12.6{\pm}0.7%$ specific NK activity for saline, B-DC and C-DC treated group, respectively). Conclusion: Conclusively, promising data were obtained that allogeneic-tumor cell lysate can be used as a tumor antigen for DC-based cancer immunotherapy.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.40-45
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• 1998

Backgroud and Objectives: Major salivary gland tumor is a rare disease with a largely unknown origin. And also corresponding to the diversity of histopathologic characteristics is an equally wide distribution of clinical behavior that makes treatment decisions difficult. The aim of this study is to analysis the clinical experience of our major salivary gland tumor and to suggest a guidline of management. Materials and Methods : We studied clinical manifestations and treatment results of 104 patients who were diagnosed as major salivary gland tumors. Tumor site, patient age and sex of the patients were analysed. Histopathologic diagnosis, treatment modality, lymph nodes metastasis, recurrence rate and 5-year survival rate were studied on malignant tumors. Results: 1) 48 patients were male and 56 patients were female. 2) Benign tumors were 79 cases. They consisted of 57 cases(72%) of parotid tumor, 22 cases(27%) of submandibular tumor. And pleomorphic adenoma was the most common benign tumor. 3) Malignant tumors were 25 cases and were consisted of 19 cases(76%) of parotid tumor, 4 cases(l6%) of submandibular tumor and 2 cases(8%) of sublingual gland tumor with high-grade mucoepidermoid carcinoma as the most common cause. 4) In the malignant tumors, the number of stage I, II tumors was 14 and that of stage III, IV tumors was 11. Neck node metastasis was noted in 8 cases. 5) 8 cases of malignant tumor were died and all of them had high-grade malignancy. And they were dead before 17 months from the time of diagnosis. 6) Mean survival duration in the malignant salivary gland tumor was 56 months. 7) High-grade malignancy had a 5-year survival rate of 57.9%. A 5-year survival rate of TI, T2 patients was 92.9% and that of T3, T4 patients was 36.4%. That of patients who had neck node metastasis was 37.5% and that of those who had tree neck was 82.4%. Conclusion: The results of this study suggest that the survival rate is dependent on the tumor size, lymph node matastasis and histologic grade. And also the early diagnosis and radical surgery result in the increased survival rate and are effective for prevention of the tumor recurrance.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.691-694
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• 2014

Background: Tumor length in patients with esophageal cancer (EC) has recently received great attention. However, its prognostic role for EC is controversial. The purpose of our study was to characterize the prognostic value of tumor length in EC patients and offer the optimum cut-off point of tumor length by reliable statistical methods. Materials and Methods: A retrospective analysis was conducted on 71 consecutive patients with EC who underwent surgery. ROC curve analysis was used to determine the optimal cut-off point for tumor length, measured with a handheld ruler after formalin fixation. Correlations between tumor length and other factors were surveyed, and overall survival (OS) rates were compared between the two groups. Potential prognostic factors were evaluated by univariate Kaplan-Meier survival analysis. A P value less than 0.05 was considered significant. Results: There were a total of 71 patients, with a male/female divide of 43/28 and a median age of 59. Characteristics were as follows: squamous/adenocarcinoma, 65/6; median tumor length, 4 (0.9-10); cut-off point for tumor length, 4cm. Univariate analysis prognostic factors were tumor length and modality of therapy. One, three and five year OS rates were 84, 43 and 43% for tumors with ${\leq}4cm$ length, whereas the rates were 75, 9 and 0% for tumors >4 cm. There was a significant association between tumor length and age, sex, weight loss, tumor site, histology, T and N scores, differentiation, stage, modality of therapy and longitudinal margin involvement. Conclusions: Future studies for modification of the EC staging system might consider tumor length too as it is an important prognostic factor. Further assessment with larger prospective datasets and practical methods (such as endoscopy) is needed to establish an optimal cut-off point for tumor length.

• Korean Journal of Head & Neck Oncology
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• v.21 no.2
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• pp.201-207
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• 2005

Purpose: Submandibular gland tumor is rare, less than 6% of head and neck tumor. The purpose of this article is to analysis the clinical experience and treatment outcomes of malignant submandibular gland tumor, suggesting a guideline of management. Methods: We retrospectively evaluated 26 patients who underwent operation for malignant submandibular gland tumor at Severence hospital between 1986 and 2004. Statistical analysis was performed by Kaplan-Meier method, log rank test, Chi-square test, Fisher's exact test using SPSS v12.0 for Windows. Results: They consisted of 18 males and 8 females whose median age was 47 years(range: 20-71). 10 cases of adenocystic carcinoma, 8 cases of carcinoma ex pleomorphic adenoma, 4 cases of mucoepidermoid carcinoma, 1 case each for acinic cell carcinoma, undifferentiated carcinoma, adeno carcinoma, epithelioid hemangioendothelioma. Sialoadenectomy only was performed in 10 cases(36.5%) and sialoadenectomy with neck node dissection was performed in 16 cases(63.5%). Adjuvant radiotherapy was done in 22 cases(84.6%). 10 year disease free survival rate for malignant submandibular gland tumor was 63.1 % and 10 year overall survival rate for malignant submandibular gland tumor was 70.1%. In univariate analysis, prognostic factors affecting recurrence of malignant submandibular gland tumor was initially papable lateral neck node in physical examination and metastasis of lateral neck node in pathologic confirmation. The prognostic factors affecting survival of malignant submandibular gland tumor was tumor size, TNM stage, recurrence and type of recurrence. Conclusion: In this study, prognostic factors affecting recurrence of malignant submandibular gland tumor was initially papable lateral neck node in physical examination and metastasis of lateral neck node in pathologic confirmation. The prognostic factors affecting survival of malignant submandibular gland tumor was tumor size, TNM stage, recurrence and type of recurrence. To prevent recurrence and to improve survival, early diagnosis and aggressive surgery must be considered.

• 대한방사선치료학회:학술대회논문집
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• 2005.06a
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• pp.23-26
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• 2005

Introduction: To evaluate whether modified MUPIT applicator can effectively eradicate recurrent tumor in uterine cervix cancer and reduce rectal complication after complete radiation treatment. Methods and Materials: Modified MUPIT applicator basically consists of an acrylic cylinder with flexible brain applicator , an acrylic template with a predrilled array of holes that serve as guides for interstitial needles and interstitial needles. CT scan was performed to determine tumor volume and the position of interstitial needles. Modified MUPIT applicator was applied to patient in operation room and the accuracy for position of interstitial needles in tumor volume was confirmed by CTscan. Brachytherapy was delivered using modified MUPIT applicator and RALS (192-Ir HDR) after calculated computer planning by orthogonal film. The daily dose was 600cGy and the total dose was delivered 3000cGy in tumor volume by BID. Rectal dose was measured by TLD at 5 points so that evaluated the risk of rectal complication. Result: The application of modified MUPIT applicator improved dramatically dose distributions in tumor volume and follow-up of 3 month for this patient was clinically partial response without normal tissue complication, Rectal dose was measured 34.1cGy, 57.1cGy, 103.8cGy, 162.7cGy, 165.7cGy at each points, especially the rectal dose including previous EBRT and ICR was 34.1cGy, 57.1cGy Conclusion: Patients with locally recurrent tumor in uterine cervix cancer treated with modified MIUPIT applicator can expect reasonable rates of local control. The advantages of the system are the fixed geometry Provided by the template and cylinders, and improved dose distributions in irregular tumor volume without rectal complication

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.29-32
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• 2014

Background and Objective: Lung cancer is one of the malignant diseases which most seriously threat humansurvival and development. This study aimed to assess osteopontin (OPN) expression in non-small cell lung cancer (NSCLC) and any relationship with clinicopathological features. Methods: Immunohistochemistry was used to determine OPN expression and microvascular density (MVD) in 120 cases of NSCLC also undergoing clinical assessment. Results: Moderately positive expression of OPN was found in 34.6% (41/120) and strong expression in 47.5% (57/120) of the NSCLCs; OPN expression in carcinomas was higher than in pericarcinoma tissues (P<0.05). While no obvious association was observed with NSCLC patient age, gender, maximum diameter of the tumor and pathological type, OPN expression was more commonly detected in poorly differentiated carcinoma tissue and lymph node metastasis as well as at advanced clinical stage (P<0.05); OPN expression in cancer tissue was positively correlated with MVD (r = 0.839, P = 0.000). Conclusion: OPN plays an important role in promoting tumor angiogenesis and progress of NSCLCs and has the possibility to become the new target for therapy.

• Journal of Life Science
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• v.28 no.8
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• pp.992-998
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• 2018

Cancer cells grow in an environment composed of various components that supports tumor growth. Major cell types in the tumor microenvironment are fibroblast, endothelial cells and immune cells. All of these cells communicate with cancer cells. Among infiltrating immune cells as an abundant component of solid tumors, macrophages are a major component of the tumor microenvironment and orchestrates various aspects of immunity. The complex balance between pro-tumoral and anti-tumoral effects of immune cell infiltration can create a chronic inflammatory microenvironment essential for tumor growth and progression. Macrophages express different functional programs in response to microenvironmental signals, defined as M1 and M2 polarization. Tumor-associated macrophages (TAM) secret many cytokines, chemokines and proteases, which also promote tumor angiogenesis, growth, metastasis and immunosuppression. TAM have multifaceted roles in the development of many tumor types. TAM also interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. TAM obtain various immunosuppressive functions to maintain the tumor microenvironment. TAM are characterized by their heterogeneity and plasticity, as they can be functionally reprogrammed to polarized phenotypes by exposure to cancer-related factors, stromal factors, infections, or even drug interventions. Because TAMs produce tumor-specific chemokines by the stimulation of stromal factors, chemokines might serve as biomarkers that reflect disease activity. The evidence has shown that cancer tissues with high infiltration of TAM are associated with poor patient prognosis and resistance to therapies. Targeting of TAM in tumors is considered a promising therapeutic strategy for anti-cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.489-494
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• 2014

Background: Psychiatric patients appear to be at lower risk of cancer. Some antipsychotic drugs might have inhibitory effects on tumor growth, including penfluridol, a strong agent. To test this, we conducted a study to determine whether penfluridol exerts cytotoxic effects on tumor cells and, if so, to explore its anti-tumor mechanisms. Methods: Growth inhibition of mouse cancer cell lines by penfluridol was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cytotoxic activity was determined by clonogenic cell survival and trypan blue assays. Animal tumor models of these cancer cells were established and to evaluate penfluridol for its anti-tumor efficacy in vivo. Unesterified cholesterol in cancer cells was examined by filipin staining. Serum total cholesterol and tumor total cholesterol were detected using the cholesterol oxidase/p-aminophenazone (CHOD-PAP) method. Results: Penfluridol inhibited the proliferation of B16 melanoma (B16/F10), LL/2 lung carcinoma (LL/2), CT26 colon carcinoma (CT26) and 4T1 breast cancer (4T1) cells in vitro. In vivo penfluridol was particularly effective at inhibiting LL/2 lung tumor growth, and obviously prolonged the survival time of mice bearing LL/2 lung tumors implanted subcutaneously. Accumulated unesterified cholesterol was found in all of the cancer cells treated with penfluridol, and this effect was most evident in LL/2, 4T1 and CT26 cells. No significant difference in serum cholesterol levels was found between the normal saline-treated mice and the penfluridol-treated mice. However, a dose-dependent decrease of total cholesterol in tumor tissues was observed in penfluridol-treated mice, which was most evident in B16/F10-, LL/2-, and 4T1-tumor-bearing mice. Conclusion: Our results suggested that penfluridol is not only cytotoxic to cancer cells in vitro but can also inhibit tumor growth in vivo. Dysregulation of cholesterol homeostasis by penfluridol may be involved in its anti-tumor mechanisms.