• International Journal of Oral Biology
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• v.34 no.2
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• pp.61-72
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• 2009

Chios gum mastic (CGM) is a resin produced from the stem and leaves of Pistiacia lentiscus L var chia, a plant which grows only on Chios Island in Greece. CGM has been used for many centuries as a dietary supplement and folk medicine for stomach and duodenal ulcers in many Mediterranean countries and is known also to induce cell cycle arrest and apoptosis in some cancer cells. In this study, we further investigated the induction and mechanisms underlying the apoptotic response to CGM treatment in the SCC25 human tongue squamous cell carcinoma cell line. The viability of SCC25 cells, human normal keratinocytes (HaCaT cells) and human gingival fibroblasts (HGF-1 cells), and the growth inhibition of SCC25 cells were assessed by MTT assay and clonogenic assay, respectively. Staining with Hoechst and hemacolor dyes and TUNEL assays were employed to detect SCC25 cells undergoing apoptosis. SCC25 cells were treated with CGM, and this was followed by western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, MMP activity and proteasome activity analyses. CGM treatment of SCC25 cells was found to result in a time- and dosedependent decrease in cell viability, a dose-dependent inhibition of cell growth, and apoptotic cell death. Interestingly, CGM showed a remarkable level of cytotoxicity in SCC25 cells but not in normal cells. Tested SCC25 cells also showed several lines of apoptotic manifestation. Taken together, our present findings demonstrate that CGM strongly inhibits cell proliferation by modulating the expression of G1 cell cycle-related proteins and induces apoptosis via the proteasome, mitochondria and caspase cascades in SCC25 cells.

• Archives of Plastic Surgery
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• v.35 no.3
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• pp.255-260
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• 2008

Purpose: Tongue cancer is the most common malignant tumor of the oral cavity and the ultimate goal in treatment of the cancer is not only complete excision and meticulous closure of the wound, but also, reconstruction of a demensional and functional tongue. Our study focuses on various factors, such as defect size, extent of tumor, age, application of mandibulectomy or radiotherapy, and their influences on postoperative speech and swallowing function. Methods: Our study was based on 59 patients who underwent tongue cancer operation and reconstruction of the tongue. Speech and swallowing were evaluated according to categories documented by Sultan and Teichgraeber. Patients were classified into 3 groups as partial glossectomy, hemiglossectomy and total glossectomy groups for evaluation. The average age of the patients were 51, and the mean follow-up period was 4 years 2 months. Results: The partial glossectomy group showed statistically relevant results for speech articulation and swallowing abilities compared to the total glossectomy group. In cases of defects involving the mouth floor, the group showed decreased results compared to the group without mouth floor involvement. Increased age showed decreased postoperative results with statistical significance, while mandibulectomy and radiotherapy revealed no statistically significant data. Analysis according to TNM staging resulted in decreased functional result with advanced staging without statistical significance. Conclusion: To summarize the factors influencing the functional outcome in tongue reconstruction, younger patients and early stage cancer with minimal surgical extent revealed more satisfying results while mandibulectomy and radiation did not have influence on our analysis. Addition of various influencing factors and studies with longer follow up periods on our patient groups may provide effective data for more satisfying functional outcomes in the future.

• Environmental Analysis Health and Toxicology
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• v.10 no.1_2
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• pp.21-35
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• 1995

Risk assessment processes, which include processes for the estimation of human cancer potency using animal bioassay data and calculation of human exposure, entail uncertainties. In the exposure assessment process, exposure scenarios with various assumptions could affect the exposure amount and excess cancer risk. We compared risk estimates among various exposure scenarios of vinyl chloride, trichloroethylene and tetrachloroethylene in tap water. The contaminant concentrations were analyzed from tap water samples in Seoul from 1993 to 1994. The oral and inhalation cancer potencies of the contaminants were estimated using multistage, Weibull, lognormal, and Mantel-Bryan model in TOX-RISK computer software. In the first case, human excess cancer risk was estimated by the US EPA method used to set the MCL(maximum contaminant level). In the second and third case, the risk was estimated for multi-route exposure with and without adopting Monte-Carlo simulation, respectively. In the second case, exposure input parameters and cancer potencies used probability distributions, and in the third case, those values used point estimates(mean, and maximum or 95% upper-bound value). As a result, while the excess cancer risk estimated by US EPA method considering only direct ingestion tended to be underestimated, the risk which was estimated by considering multi-route exposure without Monte-Carlo simulation and then using the maximum or 95% upper-bound value as input parameters tended to be overestimated. In risk assessment for volatile organic compounds, considering multi-route exposure with adopting Monte-Carlo analysis seems to provide the most reasonable estimations.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1073-1075
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• 2013

Background: In normal cells, activated epidermal growth factor receptor (EGFR) molecules are subjected to ubiquitination-mediated proteasome degradation pathway by c-Cbl, an ubiquitin ligase that checks uncontrolled proliferation. Hence expression of wild type c-Cbl molecule is essential to keep this degradation machinery in a functional state. Loss of expression or function of c-Cbl may consequently lead to sustained activation of EGFR and promote carcinogenesis, loss of function mutations in the c-Cbl gene already being reported in lung and hematopoietic cancers. However, the genetic status of c-Cbl in oral squamous cell carcinoma (OSCC) is not known. Hence in the present study we investigated the genomic DNA isolated from OSCC tissue biopsy samples for mutations in the RING finger domain coding region of c-Cbl gene, which has also been reported to be most frequently mutated in other cancers. Materials and Methods: Total genomic DNA isolated from thirty two post surgical OSCC tissue samples were amplified using primers flanking the exon 8 of c-Cbl gene that codes for the RING finger domain. The PCR amplicons were then resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations. Results: The sequencing data of the thirty two OSCC samples did not identify mutations in the RING finger domain coding region of c-Cbl gene. Conclusions: To the best of our knowledge, this is the first time that the genetic status of c-Cbl gene in OSCC samples has been investigated. The present data indicates that genetic alteration of RING finger domain coding region of c-Cbl gene is relatively infrequent in OSCC samples.

• Imaging Science in Dentistry
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• v.50 no.2
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• pp.81-92
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• 2020

Intelligent systems(i.e., artificial intelligence), particularly deep learning, are machines able to mimic the cognitive functions of humans to perform tasks of problem-solving and learning. This field deals with computational models that can think and act intelligently, like the human brain, and construct algorithms that can learn from data to make predictions. Artificial intelligence is becoming important in radiology due to its ability to detect abnormalities in radiographic images that are unnoticed by the naked human eye. These systems have reduced radiologists' workload by rapidly recording and presenting data, and thereby monitoring the treatment response with a reduced risk of cognitive bias. Intelligent systems have an important role to play and could be used by dentists as an adjunct to other imaging modalities in making appropriate diagnoses and treatment plans. In the field of maxillofacial radiology, these systems have shown promise for the interpretation of complex images, accurate localization of landmarks, characterization of bone architecture, estimation of oral cancer risk, and the assessment of metastatic lymph nodes, periapical pathologies, and maxillary sinus pathologies. This review discusses the clinical applications and scope of intelligent systems such as machine learning, artificial intelligence, and deep learning programs in maxillofacial imaging.

• Microbiology and Biotechnology Letters
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• v.22 no.4
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• pp.368-372
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• 1994

Three more unusual macrolides in addition to concnamycin B were isolated from the mycelium of Streptomyces sp. strain Bal6. These four compounds showed a potent cytotoxity to hunian cancer cell lines, SNU-1 (stomach cancer cell line), SNU-354 (liver cancer cell line), MCF- 7 (breast cancer cell line) and KB-3-1 (oral epidermoid carcinoma cell line). Interestingly, these compounds confered slight differential cytotoxity on RHEK-1, a human epidermal keratinocyte cell line immotalized by AD12-SV40 hybrid virus and RHEK-1/pSV$_{2}$ ras which was resulted from H-ras transfomation of RHEK-1. These compounds were determined to be concanamycin A, conca- namycin E and 0-methyl concanamycin B by NMR and other spectral analysis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4117-4123
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• 2016

Background: Methylation of promoter 2 of the SHP1 gene is epithelial cell specific, with reported potential as a lymph node metastatic marker. Objective: To demonstrate SHP1-P2 methylation-specific quantitative PCR effectiveness in detecting colorectal cancer (CRC) DNA in lymph nodes. Materials and Methods: SHP1-P2 methylation levels were measured in lymph nodes of CRC patients and compared with pathological findings and patient prognosis. Results: Lymph nodes of CRC metastatic patients without microscopically detectable cancer cells had higher SHP1-P2 methylation levels than lymph nodes of controls (p<0.001). In addition, a higher SHP1-P2 methylation level was associated with a shorter duration until adverse disease events, metastasis, recurrence and death (r2 = 0.236 and p value = 0.048). Studying two cohorts of 74 CRC patients without microscopic lymph node metastases showed that only the cohort containing samples with high SHP1-P2 methylation levels had a significant hazard ratio of 3.8 (95%CI = 1.02 to 14.2). Conclusions: SHP1-P2 methylation PCR can detect CRC DNA in lymph nodes even if cancer cells are not visible under a microscope, confirming applicability as a potential universal lymph node metastatic marker.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6219-6225
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• 2014

Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

• Journal of Oral Medicine and Pain
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• v.32 no.3
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• pp.251-261
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• 2007

Bile acids and synthetic its derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. Previous studies have been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis inducing activity on various cancer cells in vitro. It wasn't discovered those materials have apoptosis induced effects on YD9 human oral squamous carcinoma cells. The present study was done to examine the synthetic bile acid derivatives(HS-1199, HS-1200) induced apoptosis on YD9 cells and such these apoptosis events. We administered them in culture to YD9 cells. Tested YD9 cells showed several lines of apoptotic manifestation such as activation of caspase-3, degradation of DFF, production of poly (ADP-ribose) polymerase(PARP) cleavage(HS-1200 only), DNA degradation(HS-1200 only), nuclear condensation, inhibition of proteasome activity, reduction of mitochondrial membrane potential(HS-1200 only) and the release of cytochrome c and AIF to cytosol. Between two synthetic CDCA derivatives, HS-1200 showed stronger apoptosis-inducing effect than HS-1199. Therefore HS-1200 was demonstrated to have the most efficient antitumor effect. Taken collectively, we demonstrated that a synthetic CDCA derivative HS-1200 induced caspases-dependent apoptosis via mitochondrial pathway in human oral sqauamous carcinoma cells in vitro. Our data therefore provide the possibility that HS-1200 could be considered as a novel therapeutic strategy for human orall squamous carcinoma from its poweful apoptosis-inducing activity.

• International Journal of Oral Biology
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• v.46 no.4
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• pp.176-183
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• 2021

Oral squamous cell carcinoma (OSCC) metastasis is characterized by distant metastasis and local recurrence. Combined chemotherapy with cisplatin and 5-fluorouracil is routinely used to treat patients with OSCC, and the combined use of gefitinib with cytotoxic drugs has been reported to enhance the sensitivity of cancer cells in vitro. However, the development of drug resistance because of prolonged chemotherapy is inevitable, leading to a poor prognosis. Therefore, understanding alterations in signaling pathways and gene expression is crucial for overcoming the development of drug resistance. However, the altered characterization of Ca²⁺ signaling in drug-resistant OSCC cells remains unclear. In this study, we investigated alterations in intracellular Ca²⁺ ([Ca²⁺]_i) mobilization upon the development of gefitinib resistance in human tongue squamous carcinoma cell line (HSC)-3 and HSC-4 using ratiometric analysis. This study demonstrated the presence of altered epidermal growth factor- and purinergic agonist-mediated [Ca²⁺]_i mobilization in gefitinib-resistant OSCC cells. Moreover, Ca²⁺ content in the endoplasmic reticulum, store-operated calcium entry, and lysosomal Ca²⁺ release through the transient receptor potential mucolipin 1, were confirmed to be significantly reduced upon the development of apoptosis resistance. Consistent with [Ca²⁺]_i mobilization, we identified modified expression levels of Ca²⁺ signaling-related genes in gefitinib-resistant cells. Taken together, we propose that the regulation of [Ca²⁺]_i mobilization and related gene expression can be a new strategy to overcome drug resistance in patients with cancer.