• Reproductive and Developmental Biology
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• v.29 no.2
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• pp.101-108
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• 2005

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a well-known inducer of apoptotic cell death in many tumor cells. 1RAIL is expressed in human placenta, and cytotrophoblast cells express 1RAIL receptors. However, the role of TRAIL in human placentas and cytotrophoblast cells is not. well understood. In this study a trophoblast cell line, JEG-3, was used as a model system to examine the effect of TRAIL. on key intracellular signaling pathways involved in the control of trophoblastic cell apoptosis and survival JEG-3 cells expressed receptors for 1RAIL, death receptor (DR) 4, DR5, decoy receptor (OcR) 1 and DeR2. Recombinant human TRAIL (rhTRAIL) did not have a cytotoxic effect determined by MIT assay and did not induce apoptotic cell death determined by poly-(ADP-ribose) polymerase cleavage assay. rhTRAIL induced a rapid and transient nuclear translocation of nuclear $factor-{\kappa}B(NF-{\kappa}B)$ determined by immunoblotting using nuclear protein extracts. rhTRAIL rapidly activated extracellular signal-regulated protein kinase (ERK) 1/2 as determined by immnoblotting for phospho-ERK1/2. However, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38MAPK) and Akt (protein kinase B) were not activated by rhTRAIL. The ability of 1RAIL to induce $NF-{\kappa}B$ and ERK1/2 suggests that interaction between TRAIL and its receptors may play an important role in trophoblast cell function during pregnancy.

• Journal of Korean Neurosurgical Society
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• v.40 no.4
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• pp.245-248
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• 2006

Objective : To evaluate the effectiveness of Novalis shaped beam radiation treatment as an adjuvant treatment in patients with craniopharyngiomas. Methods : We reviewed 8 patients with craniopharyngiomas who had recurring tumors during follow-up or had residual lesions after primary surgery. Three of 8 patients were found to have recurrence after gross total excision of the tumor and 5 patents had residual lesions after subtotal resection. All patients were treated with fractionated stereotactic radiation treatment[FSRT] using Novalis system. The mean age of patients was 28 years [range $16{\sim}52$]. The median irradiation dose per fraction was 17Gy [range $1.7{\sim}2.0$]. The median fraction number was 23 [range $15{\sim}25$], and the median total dose was 39.1 Gy [range $25.5{\sim}42.5$]. Follow-up included MR imaging, and ophthalmologic and endocrine examinations. Results : The median follow-up period was 23 months [range $12{\sim}43$]. The local tumor control rate was 87.5%. One patient had a recurring tumor, in which cystic change developed 2 months after FSRT. Four patients showed a decrease in size of their tumor, while 3 patients remained stable. Seven out of 8 patients had hormonal dysfunction that remained unchanged after initial surgery. No further progression of visual impairment was observed. Conclusion : FSRT using Novais system is effective and safe for the treatment of recurring or residual craniopharyngiomas without toxicity like optic neuropathy.

• Molecules and Cells
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• v.24 no.1
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• pp.132-138
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• 2007

4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily, is expressed on activated T-cells, and 4-1BB signaling due to interaction with 4-1BB ligand or ligation with anti-4-1BB monoclonal antibody (mAb) costimulates T cells. It has been shown that administration of anti-4-1BB mAb induces anti-tumor immunity in mice, but the nature of the cellular subsets responsible for this immunity is uncertain. In this study we found that anti-4-1BB mAb administration to B16F10 melanoma-bearing mice induced marked expansion of $CD11c^+CD8^+$ T-cells in parallel with suppression of pulmonary tumors. The mAb-treated mice produced higher levels of $IFN-{\gamma}$ in their tumor tissues, spleen and lymph nodes than mice exposed to control antibody. When the $CD11c^+CD8^+$ T-cells were purified and re-stimulated in vitro, they produced high levels of the Th1 cytokines, $IFN-{\gamma}$ and IL-2, but low levels of the Th2 cytokines, IL-4 and IL-10. Furthermore, they expressed high levels of 4-1BB and CD107a, a marker of activated cytotoxic T-lymphocytes. Our results suggest that $CD11c^+CD8^+$ T-cells play a role in the anti-tumor immunity induced by anti-4-1BB mAb.

• Korean journal of food and cookery science
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• v.21 no.5
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• pp.599-606
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• 2005

The study was carried out to measure the antitumor effect of traditional doenjang (Korean soybean paste) added with Japanese apricot, garlic or ginger. Four kinds of traditional doenjang inhibited significantly the tumor growth in mice injected sarcoma-I80 cells. Especially, traditional doenjang added with ginger (Gi-TD) showed an inhibition of tumor cell activity of 97% by the administration of 1.0 mg/kg methanol extracts. Among Balb/c mouse administered doenjang extracts, the liver weight of mice fed Gi-TD was heavier than that of the group not administered doenjang. However, no difference was found between the control and doenjang administrated groups in weights of body, spleen, kidney and heart. The activity of natural killer (NK) cells was relatively high in mice administrated with the four kinds of doenjang. Particularly, mice administrated with the Gi-TD methanol extracts showed a strong activity of 82.9%. The activity of glutathione S-transferase (GST) in mice administrated with the 4 kinds of doenjang was higher than that of the group not administered with doenjang. In particular, the GST activity was the strongest in the group administrated with Gi-TD. The results suggest that Gi-TD has a strong growth inhibition activity against sarcoma-180 tumor cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7453-7457
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• 2014

Objective: To observe the efficacy and toxicity of nanoparticle albumin bound paclitaxel (nab-paclitaxel) plus platinum agent (cisplatin or carboplatin) as first line treatment for stage III/IV squamous non-small-cell lung cancer (NSCLC). Methods: Forty chemotherapy naive patients with stage III/IV squamous NSCLC received nab-paclitaxel $125mg/m^2$ on day 1 and day 8, cisplatin $75mg/m^2$ on day 1, carboplatin area under the concentration-time curve of 5 (AUC=5) on day 1. One cycle of treatment was 3 weeks, and at least two were completed in each case. Results: Of the 40 patients who participated in the study, 25 achieved partial responses (PR), 12 reached a stage of stable disease (SD), and 3 suffered progressive disease (PD). The overall response rate (ORR) was 62.5% and the disease control rate (DCR) was 92.5%. Of the 20 patients without surgery or radiotherapy, 10 achieved PR, 7 reached a stage of SD, and 3 PD. The ORR was 50.0% and the DCR was 85.0%. The median progression-free survival time (PFS) of patients without surgery or radiotherapy was 5.0 months. Of the 20 patients receiving surgery or radiotherapy, 15 had PR and 5 p had SD, with an ORR of 75.0% and a DCR of 85.0%. Specifically, the DDP arm demonstrated a significantly higher ORR than the CBP arm (100%vs 54.5%, P<0.05). Common treatment related adverse events were myelosuppression, gastrointestinal response, baldness and neurotoxicity, most of which were grade 1 to 2. Conclusion: Nab-paclitaxel plus platinum agent (cisplatin or carboplatin) is effective as a first-line chemotheraphy for stage III/IV squamous NSCLC, and its adverse effects are tolerable.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.35-39
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• 1998

Objectives: Minimal improvement in the long-term survival of head and neck cancer(HNC) patients has occurred despite a multitude of advances in the control of loco regional disease and a second primary malignancy(SPM) contribute to the continued poor prognosis for the HNC patients. This study was performed in order to identify the clinical characteristics of SPM in the HNC patients. Materials and Methods: The medical records of 354 patients of head and neck squamous cell carcinoma that were followed up after initial treatment during the period of 1987 through 1994 were reviewed. This study examines the medical records of 354 patients with squamous cell carcinoma of the head and neck, of whom 26 subsequently developed a second neoplasm. Results: The actuarial SPM rate was 7.3%, and median time to presentation for the SPM was 26.8 months. The SPM were more likely to occur in male patients who had oral cavity index tumors. Patient whose index tumor was small at diagnosis had a greater chance of developing a second tumor as did those with no cervical lymph node metastases to the neck. Initial treatment modality was not associated with an increased risk of developing a second tumor. The commonest sites for the SPM were the lung and other head and neck area. The 3-year survival for patients who developed a secondary tumor from the time of its diagnosis was 27.8%. Conclusion: The SPM in the head and neck cancer patients are not uncommon and early detection of the SPM will contribute to increase the long-term survival of HNC patients.

• Radiation Oncology Journal
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• v.34 no.3
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• pp.216-222
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• 2016

Purpose: To evaluate the benefit of adjuvant radiation therapy (RT) for retroperitoneal liposarcoma (RPLS) following gross tumor removal. Materials and Methods: We reviewed 77 patients with primary RPLS surgically treated between January 2000 and December 2013. Cases with gross residual disease were excluded. Tumor grade was evaluated according to the French Federation of Cancer Centers Sarcoma Group (FNCLCC) system. Adjuvant RT was delivered to 32 patients (42%) using external beam RT alone. Median follow-up time was 36 months (range, 5 to 169). Results: Among 77 patients, 33 (43%) presented with well-differentiated, 31 (40%) with de-differentiated, 8 (10%) with myxoid/round and 4 (5%) with pleomorphic morphology. The RT group included less well-differentiated subtype than surgery group (28% vs. 53%). During follow up, 34 patients (44%) showed local recurrence. Local recurrence rate was lower in the RT group (38%) compared to the surgery group (49%). The 3-year local control rate (LC) was 55.6%, and the 3-year overall survival (OS) was 82.1%. Tumor histology and FNCLCC grade were significantly associated with local recurrence. There was no statistical significance of adding adjuvant RT in LC (p = 0.312). However, patients with tumor histology other than well-differentiated subtype showed marginally decreased local recurrence rate after adjuvant RT (3-year LC, RT 43.9% vs. no RT 35.3%; p = 0.087). Conclusion: RPLS patients receiving RT experienced less local recurrence. We suggest that the addition of adjuvant RT may be related to improvement of LCs, especially in patients with non-favorable histologic subtypes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1077-1082
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• 2015

Recent studies have suggested that the RAS protein activator like-1 (RASAL1) functions as a tumor suppressor in vitro and may play an important role in the development of gastric cancer. However, whether or not RASAL1 suppresses tumor growth in vivo remains to be determined. In the present study, we investigated the role of RASAL1 in gastric carcinogenesis using an in vivo xenograft model. A lentiviral RASAL1 expression vector was constructed and utilized to transfect the human poorly differentiated gastric adenocarcinoma cell line, BGC-823. RASAL1 expression levels were verified by quantitative real-time RT-PCR and Western blotting analysis. Then, we established the nude mice xenograft model using BGC-823 cells either over-expressing RASAL1 or normal. After three weeks, the results showed that the over-expression of RASAL1 led to a significant reduction in both tumor volume and weight compared with the other two control groups. Furthermore, in xenograft tissues the increased expression of RASAL1 in BGC-823 cells caused decreased expression of p-ERK1/2, a downstream moleculein the RAS/RAF/MEK/ERK signal pathway. These findings demonstrated that the over-expression of RASAL1 could inhibit the growth of gastric cancer by inactivation of the RAS/RAF/MEK/ERK pathway in vivo. This study indicates that RASAL1 may attenuate gastric carcinogenesis.

• BMB Reports
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• v.50 no.1
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• pp.1-2
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• 2017

Acquiring a selective growth advantage by breaking the proliferation barrier established by gatekeeper genes is a centrally important event in tumor formation. Removal of the mammalian Hippo kinase Mst1 and Mst2 in hepatocytes leads to rapid hepatocellular carcinoma (HCC) formation, indicating that the Hippo signaling pathway is a critical gatekeeper that restrains abnormal growth in hepatocytes. By rigorous genetic approaches, we identified an interacting network of the Hippo, Wnt/${\beta}$-catenin and Notch signaling pathways that control organ size and HCC development. We found that in hepatocytes, the loss of Mst1/2 leads to the activation of Notch signaling, which forms a positive feedback loop with Yap/Taz (transcription factors controlled by Mst1/2). This positive feedback loop results in severe liver enlargement and rapid HCC formation. Blocking the Yap/Taz-Notch positive feedback loop by Notch inhibition in vivo significantly reduced the Yap/Taz activities, hepatocyte proliferation and tumor formation. Furthermore, we uncovered a surprising inhibitory role of Wnt/${\beta}$-catenin signaling to Yap/Taz activities, which are important in tumor initiation. Genetic removal of ${\beta}$-catenin in the liver of the Mst1/2 mutants significantly accelerates tumoriogenesis. Therefore, Wnt/${\beta}$-catenin signaling, known for its oncogenic property, exerts an unexpected function in restricting Yap/Taz and Notch activities in HCC initiation. The molecular interplay between the three signaling pathways identified in our study provides new insights in developing novel therapeutic strategies to treat liver tumors.

• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.606-612
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• 2007

Since the introduction of chemotherapy for the treatment of childhood leukemia more than 50 years ago, the results of childhood cancer have improved dramatically. The 5-year survival rate of disease, many of which were uniformly fatal in the prechemotherapy era, reached to more than 75%. This remarkable improvement in survival is a direct result of the incorporation of chemotherapeutics into treatment regimens that previously relied only on surgery or radiotherapy for the primary tumor. The multimodality approach, which integrates surgery and radiotherapy to control local disease with chemotherapy to eradicate systemic or metastatic disease, has become the standard approach to treating most childhood cancers. The overall improvement in outcomes in childhood solid tumors has been related to the development of multidisplinary cooperative studies that has permitted the development of well-designed tumor treatment protocols characterized by uniform staging criteria, sharing informations in pathologic classification, uniform methods for tumor markers, oncogenes, and other biologic and genetic factors. Important advances in the biologic study of cancer and its genetic basis led to a number of observations that impact directly on the management of childhood solid tumors. Identification of specific genes, oncogenes, tumor markers, and other biologic and pathologic factors plays an important role in both staging and clarifying the risk categorization of individual patients. Treatment of the patient is influenced by the recognition of specific risk factors. This knowledge has resulted in a change in the approach to care based not only on staging criteria, but also on risk-based management. This concept uses various risk factors of outcomes. Risk-based management allows for each patient to maximize survival, minimize long-term morbidity and improve the quality of life, especially for children's growth and development.