• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3065-3070
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• 2014

Background: Neuroblastoma (NB), is a neuroectodermal tumor derived from neural crest cells, and it is the second most common pediatric malignant tumor. The biological and clinical behavior of NB is very heterogeneous. This study was conducted to evaluate the expression of Ki-67, p53 and VEGF markers in tissues obtained from NB patients with different histologic types and stage. Materials and Methods: Tissue microarray (TMA) blocks were constructed from paraffin blocks of the NB tissues. Immunohistochemical staining was performed on TMA sections to detect the expression of Ki-67, p53 and VEGF markers. The association between the expression of these markers and clinicopathological parameters were then analyzed. Results: We had 18 patients with NB, one patient with ganglioneuroblastoma (GNB) and one with ganglioneuroma. Ki-67 was expressed in 13 (65%) tumors, and negatively correlated with age, prognosis, histologic type and stage of NB (all p<0.05). High and moderate expression of VEGF was found in 5% (1/20) and 65% (13/20) of the tumors, respectively; and it was positively correlated with age, prognosis and histologic types (all p<0.05) and negatively correlated with MKI (mitosis-karyorrhexis index). p53 expression was observed in 10% (2/20) of the tumors, which showed a relative correlation with MKI (p value=0.07). Conclusions: VEGF as a candidate for anti-angiogenic targeted therapy was correlated with the development and progression of NB; therefore, VEGF along with Ki-67 can serve as a valuable marker for the prognosis of this tumor type.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3011-3015
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• 2013

Objective: This study aimed to investigate the expression of B7-H4 in human thyroid cancer and determine any association with patient clinicopathological parameters and survival. Methods: B7-H4 expression in 64 clinical thyroid cancer specimens was assessed with immunohistochemistry. Moreover, B7-H4 mRNA expression in 10 fresh resected specimens were evaluated by the reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical staining of CD3 was performed to assess the number of tumor infiltrating T lymphocytes (TILs) in thyroid cancers. Results: Positive B7-H4 immunohistochemical staining was observed in 61 out of 64 (95.3%) specimens of thyroid cancer tissues. Significantly more B7-H4 mRNA copies were found in thyroid cancer tissue than that adjacent normal tissue. Moreover, B7-H4 expression in human thyroid cancer tissues was significantly correlated with patient TNM stages and extrathyroidal extension (P<0.05), being inversely correlated with the number of TILs (P<0.05). The overall survival rate of the patients with higher B7-H4 expression was significantly worse than that of the patients with lower B7-H4 expression. Conclusions: This present study suggests that high B7-H4 expression is associated with cancer progression, reduced tumor immunosurveillance and worse patient outcomes in human thyroid cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.3
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• pp.234-238
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• 2002

Photodynamic therapy (PDT) is based on a photochemical reaction which is initiated by light activation of a photosensitizer. The photosensitizer accumulates more in tumor tissues than in normal tissues and is activated with specific wavelength of light, usually laser. The photochemical reaction produces highly reactive oxygen products causing cytotoxiciy and vascular shutdown to the tumor. The advantages of PDT are its relative selective tumor destruction and tissue healing by regeneration, which can maintain important structures with very good functional and esthetic results. Therefore, PDT is considered as an alternative modality for cancers of the head and neck. In this article, we will report three cases of photodynamic therapy for treatment of oral leukoplakia, squamous cell carcinoma, and basal cell carcinoma of head and neck. It was observed that premalignant and malignant lesions responded well to the photodynamic therapy with Aminolevulinic acid (ALA) and $Foscan^{(R)}$. Photodynamic therapy can be considered as a new treatment method for the premalignant and malignant tumors in Oral and Maxillofacial Surgery.

• Journal of Ginseng Research
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• v.40 no.3
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• pp.304-308
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• 2016

Background: Joboksansam, Korean bird wild ginseng, is an artificially cultivated wild ginseng germinated from bird feces. Although numerous pharmacologic activities of wild ginsengs have been reported, the beneficial effect of joboksansam in cancer has not been elucidated. In this study, we investigated the in vivo and in vitro anticancer activities of joboksansam powder. Methods: To evaluate the in vivo anticancer activity of joboksansam, we established a xenograft mouse model bearing RMA cell-derived cancer. Direct cytotoxicity induced by joboksansam powder was also investigated in vitro using (3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) assay. The inhibitory activity of this powder on the activation of cell survival signaling involving Akt and Src was examined with immunoblot analysis. Results: Joboksansam powder displayed strong inhibitory activity against the increased tumor size, increased weight of total body and cancer tissues, and mortality of tumor-bearing mice. Joboksansam powder also suppressed the activation of survival regulatory enzymes Akt and Src, as assessed by phosphorylation levels in the immunoblot analysis of tumor tissues. Interestingly, the viability of RMA cells in vitro was directly decreased by joboksansam treatment. Conclusion: Overall, our results strongly suggest that joboksansam powder has the potential to protect against cancer generation by direct cytotoxic effects on cancer cells resulting from suppression of cell survival signaling.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.284-290
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• 2022

Oral squamous cell carcinoma (OSCC) is mostly diagnosed at an advanced stage, with local and/or distal metastasis. Thus, locoregional and/or local control of the primary tumor is crucial for a better prognosis in patients with OSCC. Platelets have long been considered major players in cancer metastasis. Traditional antiplatelet agents, such as aspirin, are thought to be potential chemotherapeutics, but they need to be used with caution because of the increased bleeding risk. Podoplanin (PDPN)-expressing cancer cells can activate platelets and promote OSCC metastasis. However, the reciprocal effect of platelets on PDPN expression in OSCC has not been investigated. In this study, we found that direct contact with platelets upregulated PDPN and integrin β1 at the protein level and promoted invasiveness of human OSCC Ca9.22 cells that express low levels of PDPN. In another human OSCC HSC3 cell line that express PDPN at an abundant level, silencing of the PDPN gene reduced cell invasiveness. Analysis of the public database further supported the co-expression of PDPN and integrin β1 and their increased expression in metastatic tissues compared to normal and tumor tissues of the oral cavity. Taken together, these data suggest that PDPN is a potential target to regulate platelet-tumor interaction and metastasis for OSCC treatment, which can overcome the limitations of traditional antiplatelet drugs.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3719-3724
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• 2013

Background: RASSF1A has been reported to be a candidate tumor suppressor in non-small cell lung cancer (NSCLC). However, the association between RASSF1A promoter methylation and NSCLC remains unclear, particularly in regarding links to clinicopathologic features. Methods: Eligible studies were identified through searching PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also performed to evaluate publication bias. Results: Nineteen studies involving 2,063 cases of NSCLC and 1,184 controls were included in this meta-analysis. A significant association was observed between RASSF1A methylation and NSCLC in the complete data set (OR = 19.42, 95% CI: 14.04-26.85, P < 0.001). Pooling the control tissue subgroups (heterogeneous/autologous) gave pooled ORs of 32.4 (95% CI, 12.4-84.5) and 17.7 (95% CI, 12.5-25.0) respectively. Racial subgroup (Caucasian/Asian) analysis gave pooled ORs of 26.6 (95% CI, 10.9-64.9) and 20.9 (95% CI, 14.4-30.4) respectively. The OR for RASSF1A methylation in poorly-differentiated vs. moderately/well-differentiated NSCLC tissues was 1.88 (95% CI, 1.32-2.68, P<0.001), whereas there were no significant differences in RASSF1A methylation in relation to gender, pathology, TNM stage and smoking behavior among NSCLC cases. Conclusion: This meta-analysis suggests a significant association between RASSF1A methylation and NSCLC, confirming the role of RASSF1A as a tumor suppressor gene. Large-scale and well-designed case-control studies are needed to validate the associations identified in the present meta-analysis.

• Proceedings of the KSAR Conference
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• 2001.03a
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• pp.47-47
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• 2001

The neuropeptide vasopressin (VP) is a nine- amino acid hormone synthesized as preprohormone in the cell bodies of hypothalamic magnocellular neurons. The tumor in magnocellular neurons of the hypothalamus is associated with disfunctions of the cell bodies, leading to the diabetes insipidus. In order to study with the diabetes insipidus caused by a defect in VP synthesis and its secretion, we have produced the transgenic mice regulated by vasopressin promoter inserted to SV40 T antigen coding sequence (pVPSV.IGR2.1). One transgenic line expressing high levels of SV40 T antigen was propagated. The founder and all transgene positive adult animals have appeared with shorten mortality or apparent phenotypic abnormalities, including immune complex disease, and eventually die between 4 and 8 months of age. The mRNA and protein of SV40T antigen transgene were detected in brain of fetus as well as in brain, spleen, lung and lymph node in moribund at the age of 20 weeks. Histological analysis of transgenic mice showed that tumor developed in brain similar to primitive neuroectodermal tumors (PNET) in man. We also detected lymphomas in spleen and lymph node, and consequent tumor formation in various tissues of the transgenic mice. In pVPSV.IGR2.1, 21% mice showed brain tumor (PNET) at 5 weeks and 100% mice showed brain tumor after 15 weeks. In addition, Expression of apoptosis related genes (Bcl-28 & Bax) was increased over their age in mice with PNET as compared to control mice. Apoptosis related gene expression might be deregulated in mice with brain tumor. However, transgenic mice were not developed with the diabetes insipidus. These mice represent the first disease model to exhibit primitive neuroectodermal tumor in brain, as well as a unique model system for exploring the cellular pathogenesis of lymphomas.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4147-4151
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• 2012

The current study was conducted to explore the inhibitory effects of a small interfering RNA (siRNA) on 3-phosphoinositide-dependent protein kinase 1 (PDK1) expression in esophageal cancer 9706 (EC9706) cells and the influence on their biological behavior. After transfection of a synthesized PDK1 siRNA, PDK1 mRNA and protein expression and the phosphorylation level of the downstream Akt protein were assessed using RT-PCR and Western blot analysis. Proliferation, apoptosis, cell invasion and in vivo tumor formation capacity were also investigated using MTT, flow cytometry, Transwell invasion trials, and nude mouse tumor transplantion, respectively. PDK1 siRNA effectively suppressed PDK1 mRNA and protein expression, and down-regulated the phosphorylation level of the Akt protein in the EC9706 cells (P < 0.05). It also inhibited cell proliferation and invasion, and promoted apoptosis; such effects were particularly obvious at 48 h and 72 h after transfection (P < 0.05). Growth of transplanted tumors was inhibited in nude mice, with decreased PDK1 expression in tumor tissues. PDK1 may be closely correlated with proliferation, apoptosis and invasion of esophageal cancer cells and thus may serve as an effective target for gene therapy.

• Korean Journal of Head & Neck Oncology
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• v.9 no.2
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• pp.227-233
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• 1993

For malignant neoplasms of salivary tissues. two of the better determinants of progosis are histologic classification and size of the neoplasm. Proper management of these tumors requires an accurate diagnosis by the pathologist and correct interpretation by the surgeon. Malignant mixed tumors account for between 3 and 13 precent of all cancers of the salivary glands and 2 percent of all tumors in these locations. The typical history of these tumors is that of slowly growing mass demonstrating a sudden increase in growth. The duration of onset of the tumor mass and the diagnosis of malignancy has been demonstrated to be 10 to 18 years. The risk of malignat transformation of a benign mixed tumor increases with the duration of the tumor. We analyzed retrospectively 13 cases of malignant mixed tumor who visited from Jan. 1985 to Dec. 1992. Mean age of the patients was 56.5 years. The origin of tumors were parotid gland 7 cases, submandibular gland 2 cases, and minor salivary gland 4 cases(palate 3 cases, tonsil pillar 1 case). According to the criteria of the AJCC on staging, stage I was 1 case, stage II 1 case, stage III 2 cases, and stage IV 9 cases. Histopathologically, carcinma ex pleomorphic adenoma were 12 cases and the true malignant mixed tumor was 1 case. The major treatment modalities were curative surgery, and radiation therapy followed. In conclusion, aggressive therapy of combined surgery and postoperative radiation therapy is required for these lesions, and patients with known or suspected benign tumor should be encouraged to undergo surgery early on in their disease to avoid malignant degeneration at a later dete.

• Journal of Korean Traditional Oncology
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• v.20 no.2
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• pp.23-36
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• 2015

Purpose : The object of this study was to observe anti-cachexic effects of Kwibi-tang extracts (KBTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Methods : Three different dosages of KBTe, 50, 100 and 200 mg/kg were orally administered once a day for 42 days from 11 days after tumor cell inoculation. Six groups, each of 8 mice per group were used in the present study. Changes on the body weight, the epididymal fat weight and serum IL-6 levels were detected with the thicknesses of deposited cervical brown adipose tissue and their mean diameters to monitor the tumor-related anticachexic effects. Results : Deceases on the body weight and gains were also demonstrated in tumor-bearing control with increases of serum IL-6 levels, decreases of epididymal fat pad weight, atrophic changes of cervical brown adipose tissues. These are means that tumor-related cachexia are induced by tumor cell inoculations in the present study. However, these tumor-related cachexia were markedly inhibited by all three different dosages of KBTe treatment as compared with tumor-bearing control. 5-FU showed somewhat deteriorated the tumor-related cachexia in the present study. Conclusion : The results obtained in this study suggest that over 50 mg/kg of KBTe showed favorable anticachexic effects on the NCI-H520 cell xenograft. However, detail mechanism studies should be conducted in future with the screening of the biological active compounds in this herb.