• 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.

• Korean Journal of Head & Neck Oncology
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• v.17 no.1
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• pp.59-62
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• 2001

Objectives: We report an interim result of conformal radiotherapy in a patient with early stage cancer at the base of the tongue, which developed in a previously irradiated area. Materials and Methods: A 64-year-old male patient was diagnosed with T4N0M0 supraglottic cancer. He received 72Gy of radiation therapy from 21 November 1988 to 24 February 1989. He had local failure and underwent a salvage total laryngectomy on 28 August 1989. Subsequently, he did well. In early 1999, he suffered from throat pain. He had a 2.5cm ulcerative mass at the base of his tongue, in the area that had been irradiated previously. Biopsy showed squamous cell carcinoma. After workup, he was diagnosed with base of tongue cancer with T2N0M0. Surgery was not feasible because the morbidity was not acceptable. Since it was difficult to re-irradiate the area with a curable dose using conventional 2D radiation therapy with an acceptable morbidity, we decided to try conformal radiotherapy. We used 7 static beam ports with field sizes from $7x6.4\;to\;8x8cm^2$, using 6 and 10MV photons. The fractionation regimen was 1.8Gy, 5 times per week. He received 64.8Gy in 36 fractions from 9 April 1999 to 1 June 1999. Results: In the 21 months since radiotherapy, the patient has not experienced any acute or chronic complications, such as xerostomia. He experienced relief of pain shortly after the start of radiotherapy, showed a complete response, and is still doing well. Conclusion: Conformal radiotherapy can be used to treat cancer that develops within a previously irradiated field, with curative intent.

• Journal of Oral Medicine and Pain
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• v.38 no.3
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• pp.221-233
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• 2013

Bile acids are polar derivatives of cholesterol essential for the absorption of dietary lipids and regulate the transcription of genes that control cholesterol homeostasis. Recently it have been identified the synthetic chenodeoxycholic acid (CDCA) derivatives HS-1200 and cisplatin showed apoptisis-inducing activity on various cancer cells in vivo and in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with HS-1200 and cisplatin on human tongue squamous cell carcinoma cells (SCC25 cells). To investigate whether the co-treatment with HS-1200 and cisplatin compared to each single treatment efficiently reduces the viability of SCC25 cells, MTT assay was conducted. The induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and an analysis DNA hypoploidy. Westen blot analysis and immunofluorescent staining were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following this co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) change were also assayed. In this study, co-treatment with HS-1200 and cisplatin on SCC25 cells showed several lines of apoptotic manifestation such as nuclear condensations, DNA fragmentation, reduction of MMP and proteasome activity, the increase of Bax and the decrease of Bcl-2, decrease of DNA content, the release of cytochrome c into cytosol, translocation of AIF and DFF40 (CAD) onto nuclei, and activation of caspase-9, caspase-7, caspase-3, PARP and DFF45 (ICAD) whereas each single treated SCC25 cells did not show these patterns. Although the single treatment of $25{\mu}M$ HS-1200 and $4{\mu}g/ml$ cisplatin for 24 h did not induce apoptosis, the co-treatment of these reagents prominently induced apoptosis. Therefore our data provide the possibility that the combination therapy with HS-1200 and cisplatin could be considered as a novel therapeutic strategy for human squamous cell carcinoma.

• Journal of Oral Medicine and Pain
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• v.36 no.3
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• pp.147-160
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• 2011

Eugenol (4-allyl-2-methoxyphenol) is a natural phenolic constituent extensively used in dentistry as a component of zinc oxide eugenol cement and is applied to the mouth environment. Chios gum mastic (CGM) is a resinous exudate obtained from the stem and the main leaves of Pistacia lenticulus tree native to Mediterranean areas. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with a natural product, CGM and natural phenolic compound, eugenol on SCC25 human tongue squamous cell carcinoma cell line. To investigate whether the co-treatment with eugenol and CGM compared to each single treatment efficiently reduces the viability of SCC25 cells, MTT assay was conducted. Induction and augmentation of apoptosis were confirmed by Hoechst staining, TUNEL staining and DNA hypoploidy. Westen blot analysis and immunofluorescent staining were performed to study the alterations of the expression level and the translocation of apoptosis-related proteins in co-treatment. In this study, co-treatment of with eugenol and CGM on SCC25 cells showed several lines of apoptotic manifestation such as nuclear condensations, DNA fragmentation, the increase and decrease of Bax and Bcl-2, decrease of DNA content, the release of cytochrome c into cytosol, translocation of AIF and DFF40 (CAD) onto nuclei, and activation of caspase-3, caspase-6 caspase-7, caspase-9, PARP, Lamin A/C and DFF45 (ICAD) whereas each single treated SCC25 cells did not show or very slightly these patterns. Although the single treatment of 40 ${\mu}g$/ml CGM and 0.5 mM eugenol for 24 h did not induce apoptosis, the co-treatment of these reagents prominently induced apoptosis. Therefore our data provide the possibility that combination therapy with CGM and eugenol could be considered as a novel therapeutic strategy for human oral squamous cell carcinoma.

• The Korean Journal of Cytopathology
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• v.9 no.2
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• pp.155-159
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• 1998

Fine needle aspiration cytology(FNAC) has become a popular method for the diagnosis of a wide variety of both superficial and deep-seated lesions. However, there are few reports about the potential of FNAC for the diagnosis of intraoral lesions. We experienced 44 FNACS from intraoral lesions at Asan Medical Center: 22 from the palate, 6 from the tongue, 5 from the parapharyngeal space, 5 from the lip, 2 from the floor of mouth, 1 from the buccal mucosa, and 3 from other intraoral sites. Histological confirmation was obtained in 32 cases and we analyzed 27 cases excluding 5 cases of inadequate aspirates. Diagnosis was specifically made in 19 of 27 cases(70%) including 1 mucoepidermoid carcinoma, 1 undifferentiated carcinoma, 1 chordoma, 9 pleomorphic adenomas, 1 neurofibroma, and 6 benign lesions. There were three false negative cases(sensitivity, 62.5%) and no false positive cases(specificity, 100%): Two cases diagnosed as "cystic lesion" were confirmed to be mucoepidermoid carcinomas and a case diagnosed as pleomorphic adenoma was proved to be adenoid cystic carcinoma. The results of our study suggest that FNAC is a useful technique in the diagnosis of intraoral lesion.

• Korean Journal of Head & Neck Oncology
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• v.1 no.1
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• pp.21-34
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• 1985

The authors reviewed 114 cases of malignant major and minor salivary gland tumors at Presbyterian Medical Center seen from February, 1963 to December, 1983. The results were obtained as follows; 1) Overall male and female sex ratio was 2:1. The peak age of patients with major and minor salivary gland tumor were both 5 th decade. 2) The ratio of benign and malignant tumor was 83:114. The incidence of malignancy in each group was 52% in parotid (50 patients), 75% in minor salivary gland (45 patients), 49% in submaxillary gland(18 patients) and 25% in sublingual gland (1 patient). 3) The incidence according to the anatomic primary site for minor salivary cancers was 10 cases in the nasal cavity, each 8 in the palate and the maxillary antrum, 7 in the tongue, 5 in the gum, 3 in the larynx and 2 in the buccal mucosa. 4) Adenoid cystic carcinoma was the most common cancer of minor salivary gland and malignant mixed tumor was the most common in major salivary glands, each comprising 34 cases (76%) of minor and 19 cases (28%) of major salivary gland tumors. 5) The incidence of cervical lymph node metastasis was 50% in the submaxillary gland cancers, 44% in the parotid gland cancers and 21% in malignant tumors of minor salivary glands. The highest incidence of lymph node metastasis according to histopathological classification was formed in high grade of mucoepidermoid (67%). 6) Nerve invasion was common in mucoepidermoid carcinoma. According to anatomic site, nerve invasion occurred most often in adenoid cystic carcinoma of the submaxillary gland (44%). 7) The lung was the commonest site for distant metastasis comprising 12 cases among 26 cases in which distant spread occurred. 8) The recurrence rate was 50% for major salivary gland cancer and 52% in cancer of the minor salivary gland. In accordance with pathological classification, adenocarcinoma most frequently recurred after excision. This being seen in 88% of patients undergoing definitive therapy. 9) The determinate 5 year survival rate was 78% in major salivary gland tumors, but 69% in minor salivary gland tumors.

• International Journal of Oral Biology
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• v.40 no.1
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• pp.51-61
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• 2015

Shikonin, a major ingredient in the traditional Chinese herb Lithospermumerythrorhizon, exhibits multiple biological functions including antimicrobial, anti-inflammatory, and antitumor effects. It has recently been reported that shikonin displays antitumor properties in many cancers. This study was aimed to investigate whether shikonin could inhibit oral squamous carcinoma cell (OSCC) growth via mechanisms of apoptosis and cell cycle arrest. The effects of shikonin on the viability and growth of OSCC cell line, SCC25 cells were assessed by MTT assay and clonogenic assays, respectively. Hoechst staining and DNA electrophoresis indicated that the shikonin-treated SCC25 cells were undergoing apoptosis. Western blotting, immunocytochemistry, confocal microscopy, flow cytometry, MMP activity, and proteasome activity also supported the finding that shikonin induces apoptosis. Shikonin treatment of SCC25 cells resulted in a time- and dose-dependent decrease in cell viability, inhibition of cell growth, and increase in apoptotic cell death. The treated SCC25 cells showed several lines of apoptotic manifestation as follows: nuclear condensation; DNA fragmentation; reduced MMP and proteasome activity; decrease in DNA contents; release of cytochrome c into cytosol; translocation of AIF and DFF40 (CAD) onto the nuclei; a significant shift in Bax/Bcl-2 ratio; and activation of caspase-9, -7, -6, and -3, as well as PARP, lamin A/C, and DFF45 (ICAD). Shikonin treatment also resulted in down-regulation of the G1 cell cycle-related proteins and up-regulation of $p27^{KIP1}$. Taken together, our present findings demonstrate that shikonin strongly inhibits cell proliferation by modulating the expression of the G1 cell cycle-related proteins, and that it induces apoptosis via the proteasome, mitochondria, and caspase cascades in SCC25 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1251-1254
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• 2016

Background: Oral squamous cell carcinoma (OSCC), the most common malignancy of the oral cavity, shows geographical variation with respect to the age, sex, site and habits of the population. The histolopathologic grade of the tumor is closely related to its tissue of origin. This study was conducted to establish the prevalence of OSCC in relation to patient sex, age, habits and sites of lesions. Materials and Methods: A total of 130 cases of histopathologically diagnosed OSCC were selected for the study, out of which 66, 38 and 26 were well (WD), moderately (MD)and poorly differentiated (PD), respectively. Sections were stained with haematoxylin and eosin and graded according to a modified Borders's system. Then statistically analyzed different grades of OSCC for correlations with other variables. Results: In our study the majority cases of OSCC were found in the 5th to 7th decades of life, males acconting for 53%. The most common site was the buccal mucosa and most cases had habit of tobacco use either in the form of chewing or smoking or both. When the different grades of OSCC were compared with different sites a statistically significant value was observed (P=0.029). Conclusions: The incidence of high grade PD is very much less in female patients but in males such lesions were common. In our location population the buccal mucosa is the most common site due to the tobbaco habits of the patients and majority cases of the buccal mucosa are WD whereas in tongue, floor of the mouth and palate PD are common.

• Radiation Oncology Journal
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• v.2 no.2
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• pp.191-202
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• 1984

Biological behavior and treatment results of 33 patients with Adenoid Cystic Carcinoma (ACC) in the Head and Neck at Yonsei Cancer Confer for 10 years between 1971 and 1980 were retrospectively analysed. Most common, primary site was minor salivary glands such as maxillary sinus, nasal cavity and base of tongue. The typical biological behavior of these tumors was very slowly in growth with long time of duration(mean 19 months) from 1 month to 10 years and more frequent of nerve invasion but rare invasion of neck nodes. Local control and failure pattern in the results of treatment, 16 of 17 patients with irradiation alone were seen complete or partial response but 5 cases of locoregional recurrence, 2 cases of failure of neck node and 4 cases of distant metastasis as lung and brain. On the other hand, among 10 cases of surgery and postoperative irradiation, 2 cases of locoregional failure and 3 cases of distant metastasis as lung and bone. 2 of 4 cases with surgery alone were recurred within primary site. Actuarial overall NED survival at 3 ana 10 years were $52.6\%$ and $42.8\%$, respectively. Survival rate of 10 Patients with surgery and Postoperative irradiation was more high than 17 Patients of radiation alone. Therefore, we have known that surgery with postoperative adjunctive irradiation is most effective treatment modality of adenoid cystic carcinoma in the head and neck. Primary site, treatment modality and with or without nerve ana bone invasion have influenced on prognosis.

• Journal of Korean society of Dental Hygiene
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• v.14 no.4
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• pp.601-608
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• 2014

Objectives : The purpose of the study is to examine the apoptotic effects of Pseudomonas aeruginosa exotoxin A(PEA) in squamous cell carcinoma(SCC) 25 cells. Methods : Cell growth reduction and apoptosis induced by PEA were confirmed by WST-1 assay, Hoechst 33258 staining, flow cytometry analysis, and Western blot assay. Results : The PEA treatment decreased the cell viability in a dose and time dependent manner: control; $100{\pm}0^e$(p<0.01), 0.1875 nM; $87{\pm}4.36^d$(p<0.01), 0.375 nM; $82{\pm}0.58^d$(p<0.01), 0.75 nM; $72{\pm}1.67^c$(p<0.01), 1.5 nM; $51{\pm}1.53^{bc}$(p<0.01), 7.5 nM; $31{\pm}1.20^{ab}$(p<0.01), 15 nM; $26{\pm}0.67^a$(p<0.01), control; $100{\pm}0^a$(p<0.05), 24 h; $51{\pm}1.53^b$(p<0.05), 48 h; $16{\pm}0.5^c$(p<0.05), 72 h; $12{\pm}1.67^d$%(p<0.05). The PEA was observed on SCC 25 cells with the half maximal inhibitory concentration(IC50) value of 1.5 nM at 24 hours. The PEA treated SCC 25 cells demonstrated several types of apoptotic indications, such as nuclear condensation, the increase of sub G1, and the cleavage of PARP-1 and DFF 45. Conclusions : PEA showed anti-cancer activity against SCC 25 cells via apoptosis. PEA may potentially contribute to human oral cancer treatment.