• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.2
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• pp.97-108
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• 2011

Cancer stem cells have stem cell-like features, such as the ability for self-renewal and differentiation but show unlimited growth because they have the lost normal regulation of cell growth. Cancer stem cells and normal stem cells have similar features. They show high motility, diversity of progeny, robust proliferative potential, association with blood vessels, immature expression profiles, nestin expression, epidermal growth factor (EGF)-receptor expression, phosphatase and tensin homolog (PTEN) expression, hedgehog pathway activity, telomerase activity, and Wnt pathway activity. On the other hand, with cancer cells, some of these signaling pathways are abnormally modified. In 1875, Cohnheim suggested the concept of cancer stem cells. Recently, evidence for the existence of cancer stem cells was identified. In 1994, the cancer stem cells' specific cell surface marker for leukemia was identified. Since then, other specific cell surface markers for cancer stem cells in solid tumors (e.g. breast and colon cancer) have been identified. In oral cancer, studies on cancer stem cells have been performed mainly with squamous cell carcinomas. Oral cancer specific cell surface markers, which are genes strongly expressed in oral cancer and cancer stem cell specific side populations, have been identified. Cancer stem cells are resistant to radiotherapy and chemotherapy. Therefore, to eliminate malignant tumors efficiently and reduce the recurrence rate, therapy targeting cancer stem cells needs to be performed. Currently, studies targeting the cancer stem cells' specific signaling pathways, telomerase and tumor vasculatures are being done.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.715-718
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• 2012

The current research concerns the clinicopathological significance of MHC class I chain-related protein A (MICA) expression in oral squamous cell carcinomas (OSCCs). The expression and location of MICA protein in 14 normal oral mucous and 45 cancerous and para-cancerous tissues were assessed by immunohistochemistry and levels of MICA mRNA expression in 29 cancerous and para-cancerous tissues were determined by the real-time polymerase chain reaction. Data were analyzed with the SPSS16.0 software package. MICA was found to be located in the cytoplasm and plasma membrane. Expression was higher in para-cancerous than in cancerous tissues (P < 0.05). However, no statistical difference was found between the following: 1) para-cancerous tissue with normal mucosa; 2) normal mucosa with cancerous tissue;and 3) among different clinicopathological parameters in OSCC (P > 0.05). The level of MICA mRNA was higher in OSCCs than in para-cancerous tissues, and was correlated with the regional lymph node status and disease stage (P < 0.05). The levels of MICA protein and mRNA expression differ among normal oral mucosa, para-cancerous tissue, and cancerous tissue. MICA may contribute to the tumorigenesis and progression of OSCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2815-2819
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• 2014

Background: The aim of this study was to evaluate the prognosis of patients with stage IA-IIB cervical carcinoma and to investigate a possible correlation of histology with prognosis. Materials and Methods: Two hundred fifty one patients with adenocarcinoma and squamous cell carcinoma (SCC) histology for FIGO (International Federation of Gynecology and Obstetrics) stage IA-IIB uterine cervical carcinomas at the Radiation Oncology Clinic of GH Okmeydan Training and Research Hospital between January 1996 and December 2006 were selected, analyzed retrospectively and evaluated in terms of general characteristics and survival. Disease-free survival (DFS) and overall survival (OS) was calculated using the Kaplan-Meier method and differences were compared with the log-rank test. Multivariate analysis using a Cox-proportional hazards model was used to adjust for prognostic factors and to estimate hazard ratio (HR) with 95% confidence interval (CI). Results: There was no differences between the two tumour types in age, stage, pelvic nodal metastasis, parametrial invasion, surgical margin status, DSI, LVSI, maximal tumor diameter, grade, and treatment modalities. 5-year OS and DFS were 73% and 77%, versus 64% and 69%, for SCC and adenocarcinoma, respectively (p> 0.05). Multivariate analysis revealed independent prognostic factors including pelvic nodal metastasis and resection margin status for OS (p=0.008, p=0.002, respectively). Conclusions: Prognosis of FIGO stage IA-IIB cervical cancer patients was found to be the same for those with adenocarcinoma and SCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7315-7319
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• 2013

Background: The metastasis gene osteopontin (OPN) is subject to alternative splicing, which yields three messages, osteopontin-a, osteopontin-b and osteopontin-c. Osteopontin-c is selectively expressed in invasive, but not in noninvasive tumors. In the present study, we examined the expression of OPN-c in esophageal squamous cell carcinomas (ESCCs) and assessed its value as a diagnostic biomarker. Methods: OPN-c expression was assessed by immunohistochemistry in 63 ESCC samples and correlated with clinicopathologic factors. Expression was also examined in peripheral blood mononuclear cells (PBMCs) from 120 ESCC patients and 30 healthy subjects. The role of OPN-c mRNA as a tumor marker was investigated by receiver operating characteristic curve (ROC) analysis. Results: Immunohistochemistry showed that OPN-c was expressed in 30 of 63 cancer lesions (48%)and significantly associated with pathological T stage (P=0.038) and overall stage (P=0.023). Real time PCR showed that OPN-c mRNA was expressed at higher levels in the PBMCs of ESCC patients than in those of healthy subjects (P<0.0001) with a sensitivity as an ESCC biomarker of 86.7%. Conclusion: Our findings suggest that expression of OPN-c is significantly elevated in ESCCs and this upregulation could be a potential diagnostic marker.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7843-7846
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• 2015

Background: Some matrix metalloproteinases (MMPs) are involved in invasion and metastasis of head and neck squamous cell carcinoma (HNSCC). However, there are few studies on association between stromelysin-2 (ST-2) and invasive behavior of HNSCC. The purpose of this study was to investigate Stromelysin-2 expression by immunohistochemistry. Materials and Methods: This study was conducted on 81 specimens, including 61 HNSCC and 20 non neoplastic epithelium. Sections with 5 micron thickness were prepared and stained with immunohistochemistry technique. Then expression of ST-2 was evaluated according to percentage of stained cells and intensity of staining. Data were analyzed by SPSS (V.21) using Kruskal-Wallis and Tukey tests (P<0.05). Results: The 61 HNSCC specimens were grades I 36.1%, II 34.4% and III 29.5%. The level of ST-2 expressions were moderate (++) and intensive (+++) in 21.3% and 78.7% of tumors, respectively. The ST-2 expression level was only significant between the tumors with grade I and grade III (P=0.016). Tumors presented ST-2 expression with staining intensity of mild 6.6%, moderate 26.2% and strong 67.2%. Staining intensity of ST-2 in grade I tumors was significantly lower than grade II and grade III (P<0.05), and there was no significant difference between grades II and III (P=0.99). Conclusions: According to this study, the expression of ST-2 is associated with histopathological grade and tumor differentiation in HNSCCs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3219-3222
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• 2012

A comparative study between 17 Japanese and 19 Indian patients with oral squamous cell carcinomas (OSCCs) revealed that the tumour prognostic indicator mean vessel density (MVD) count for angiogenesis was relatively high at 57.1 in Indian as compared to 39.3 in Japanese (P=0.001) cases, whereas the lymph-vessel density (LVD) count for lymphangiogenesis was lower (12.8 vs 48.0, P=0.002). Both male and female Indians had higher MVD counts, but LVD counts were only slightly lower in females. MVD count was relatively high among the cases below 65 years old in both the countries (P=0.4). Japanese cases with Tongue cancer had higher MVD count, but the Indian cases had lower LVD counts. Size-wise, T2 and T3 had higher counts of MVD both in Indian and Japanese cases. MVD and LVD count was higher in grades II and III both in Japanese and Indian cases. There was insignificant difference of the MVD counts among smokers, but the tobacco chewers in Indian cases had higher counts of MVD and LVD (P value by Bartlett test 0.35, 0.57 respectively). The hot-spots of tumour sites had variable rates of lymphocyte infiltration showed higher MVD counts in all the cases. Although the clinical characteristics and demographic variables usually relate to MVD and LVD counts, the tendency of higher values, especially among tobacco chewers, identified as the highest risk group for occurrence of oral cancer needs to be investigated further.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2145-2152
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• 2014

Background: The survival rate for oral squamous cell carcinoma (OSCC) has remained generally unchanged in the past three decades, underlining the need for more biomarkers to be developed to aid prognostication and effective management. The prognostic potential of E-cadherin expression in OSCCs has been variable in previous studies while galectin-9 expression has been correlated with improved prognosis in other cancers. The aim of the present study was to investigate the expression of galectin-9 and E-cadherin in OSCC and their potential as prognostic biomarkers. Materials and Methods: E-cadherin and Galectin-9 expression was examined by immunohistochemistry in 32 cases of OSCC of the buccal mucosa (13 with and 19 without lymph node metastasis), as well as 6 samples of reactive lesions and 5 of normal buccal mucosa. Results: The expression of E-cadherin in OSCC was significantly lower than the control tissues but galectin-9 expression was conversely higher. Median E-cadherin HSCOREs between OSCCs positive and negative for nodal metastasis were not significantly different. Mean HSCOREs for galectin-9 in OSCC without lymph node metastasis ($127.7{\pm}81.8$) was higher than OSCC with lymph node metastasis ($97.9{\pm}62.9$) but this difference was not statistically significant. Conclusions: E-cadherin expression is reduced whilst galectin-9 expression is increased in OSCC. However, the present results suggest that E-cadherin and galectin-9 expression may not be useful as prognostic markers for OSCC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3527-3531
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• 2016

Recombinant human bone morphogenetic protein-2 (rhBMP-2 ), a member of the TGF-${\beta}$ family, has been used widely in recent years to regenerate defects of the maxillary and mandible bones. Such defects are sometimes caused by resection of oral squamous cell carcinoma (OSCC) yet the biologic effects of rhBMP-2 on these carcinomas are not fully clear. The objective of this study was to determine histologically whether rhBMP-2 produces adverse effects on angiogenesis during induction of OSCC, a biologic process critical for tumor formation in an experimental model in the buccal pouch of golden Syrian hamsters. Buccal cavities were exposed to painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks, then biopsies were taken. Division was into 2 groups: a study group of 10 hamsters receiving $0.25{\mu}g/ml$ of rhBMP-2 in the $3^{rd}$ and $6^{th}$ weeks; and a control group of 10 hamsters which did not receive any additional treatment. VEGF expression and microvessel density were measured but no differences were noted between the two groups. According to this study, rh-BMP-2 does not stimulate angiogenesis during induction of OCSSs.

• Journal of Life Science
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• v.25 no.6
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• pp.686-692
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• 2015

Cancer is subject to dynamic interactions between contrary immune reactions that drive both tumor growth and suppression. Forkhead box p3 positive T cells (Foxp3 positive T cells) might support tumor promotion, while CD8 positive T cells might protect the host. The present study examined the distributions of CD8- and Foxp3-positive T cells and CD8 positive T cells/ Foxp3 positive T cells ratio in skin squamous cell carcinoma (SCC) and its precancerous lesions; it also compared this with data for basal cell carcinoma (BCC). Iimmunohistochemical staining for CD8 and Foxp3 was conducted in 20 cases of SCC, Bowen's disease (BD), actinic keratosis (AK) and BCC. The BD and SCC cases exhibited significantly increased numbers of both CD8- and Foxp3-positive T cells in their advancing regions compared with the AK and BCC cases, and the BD cases exhibited significantly lower CD8 positive T cells / Foxp3 positive T cells ratio in these regions than did the AK and BCC cases. There was no significant difference in both T cells and the ratio between BD and SCC. The degree of both T cells infiltration differed between the advancing and central areas in SCC and BCC. Immune micro-environments differ between cutaneous squamous cell tumors and BCC and differ as well among tumor compartments.

• Tuberculosis and Respiratory Diseases
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• v.73 no.1
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• pp.11-21
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• 2012

Background: While qualitative analysis of methylation has been reviewed, the quantitative analysis of methylation has rarely been studied. We evaluated the methylation status of CDKN2A, $RAR{\beta}$, and RASSF1A promoter regions in non-small cell lung carcinomas (NSCLCs) by using pyrosequencing. Then, we evaluated the association between methylation at the promoter regions of these tumor suppressor genes and the clinicopathological parameters of the NSCLCs. Methods: We collected tumor tissues from a total of 53 patients with NSCLCs and analyzed the methylation level of the CDKN2A, $RAR{\beta}$, and RASSF1A promoter regions by using pyrosequencing. In addition, we investigated the correlation between the hypermethylation of CDKN2A and the loss of $p16^{INK4A}$ immunoexpression. Results: Hypermethylation of CDKN2A, $RAR{\beta}$, and RASSF1A promoter regions were 16 (30.2%), 22 (41.5%), and 21 tumors (39.6%), respectively. The incidence of hypermethylation at the CDKN2A promoter in the tumors was higher in undifferentiated large cell carcinomas than in other subtypes (p=0.002). Hyperrmethylation of CDKN2A was significantly associated with $p16^{INK4A}$ immunoexpression loss (p=0.045). With regard to the clinicopathological characteristics of NSCLC, certain histopathological subtypes were found to be strongly associated with the loss of $p16^{INK4A}$ immunoexpression (p=0.016). Squamous cell carcinoma and undifferentiated large cell carcinoma showed $p16^{INK4A}$ immunoexpression loss more frequently. The Kaplan-Meier survival curves analysis showed that methylation level and patient survival were barely related to one another. Conclusion: We quantitatively analyzed the promoter methylation status by using pyrosequencing. We showed a significant correlation between CDKN2A hypermethylation and $p16^{INK4A}$ immunoexpression loss.