• 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.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1993.05a
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• pp.94-94
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• 1993

Squamous cell carcinoma of the oral tongue was reviewed retrospectively for the evaluation of clinical features and for the comparison between treatment modalities. Medical records of 112 patients who underwent treatment between 1916 and 1989 at Yonsei University Severance Hospital were reviewed.22 eases were excluded from this study due to incomplete treatment. Minimum follow up period was 36 months and median follow up was 41 months(range 1 to 135 months). The most common site of the tumor was lateral border of the tongue. 45.6% of the patients showed nodal metastasis. The 5-year survival rate of the patients with stage I, II was 78.8%, and those with III, IV was 20.7%. Over all 5-year survival rate was 58.5% . Survival rate of the patients treated with radiation was 19.7% in contrast to 55.7%, 66.2% in surgery plus radiation and surgery alone. The most common sites of failures were the primary site. Reducing the rate of local recurrence and more radical therapy is desired to improve the survival of this cancer.

• Radiation Oncology Journal
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• v.5 no.2
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• pp.105-110
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• 1987

Fourty nine patients with squamous cell carcinoma of oral tongue were reviewed retrospectively for the evaluation of clinical manifestation and for the comparison between therapeutic modalites. The gross shape of the tumor was infiltrative in 22, ulcerative in 12, ad ulcer-oinfiltrative type in 10 patients. Direct extension of the tumor was most commonly to the floor of the mouth. The incidence of nodal metastasis generally increased with tumor stage. $55\%$ of the patients showed neck nodal metastasis at the time of diagnosis. Ipsilateral subdigastric node were most commonly involved, followed by submandibular nodes. The 5-year survival rate of patients treated with surgery and radiotherapy was $58.7\%$ in contrast to $21.6\%$ in radiation alone group. Overall 5-year survival rate was $31\%$ In radiation alone group, half of the patients in stage I, II were locally controlled. But the local control In stage III, IV was much inferior to early lesions. Especially, of 4 patients combined with implantation technique, 3 were completely controlled. 5-year survival rate of these implanted patients was $50\%,\;49.4\%$ of patients treated over 7,000cGy survived 5 years. This was significant in contrast to $6.4\%$ of the group treated below 7,000cGy. The most common sites of failures were primary sites. In early lesions primary radiotherapy with implantation would be an appropriate treatment in cancer of oral tongue, operation reserved for radiation failure. Operation and adjuvant radiotherapy is recommended in cases of advanced disease.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.12 no.3
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• pp.23-33
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• 1990

A clinical study of selected patients with intraoral squamous cell carcinoma which were managed in the Department of Oral Oncology of Korea Cancer Center Hospital from January 1982 to August 1989 was done. And following results were obtained. 1. Males were involved more than females by intraoral squamous cell carcinoma in a ratio of 4:1. and most of the cases occurred in the 7th and 6th decades (69%). 79% of total patients and 92.5% of males were. 2. The mean duration of symptomatic period was 5.9 months. 3. The common symptoms were swelling (63%), pain (40%), ulceration (33%), and trismus (23%) 4. In the histologic findings, well differentiation comprised 58.0%. 5. The primary sites were the upper alveolar mucosa (32%), the floor of the mouth (21%), the lower alveolar mucosa (19%), tongue (14%), retromolar trigone (8%), palate (7%) and buccal mucosa (3%). 6. According to TNM system, Stage I, Stage II, Stage III, and Stage IV comprised 4%, 15%, 32%, and 49% respectively. 7. In the management of intraoral squamous cell carcinoma, surgeries were done in the 32 cases, 23 cases of which were managed by radiation therapy or chemotherapy concurrently. And radiation therapy alone was received in 35 cases. 8. Overall 3 and 5-year survival rates without regarding to stage were 27.6% and 21.4%. 9. 3-year survival rate of female patients was 47.2% and that of male patients was 22.6%. 10. 5-year survival rate was 53.9% for "early" cancer (stage I and II) and 15.6% for "advanced"cancer (stage III and IV). Survival rate of patients in the early stages of cancer appeared to be higher than that of patients with stage III and IV(p<0.05).

• 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.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5427-5432
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• 2015

Background: Oral cancer stands among the 10 top causes of cancer death in the world. Considering the role of epidemiologic information on planning and effective interventions, the present study aimed to investigate the epidemiology of oral cancer in Iran. Materials and Methods: The required information for this systematic review study was obtained from PubMed, Google Scholar, CINAHL,SID, Medlib, Magiran and Iranmedex databases, using key words "cancer", "oral cancer", "squamous cell carcinoma", "oral cavity carcinoma" and their Persian equivalents in combination with keywords of epidemiology, prevalence, etiology, frequency, and Iran from 1990 to 2014. From 1,065 related studies found, finally 25 were included to the study. Results: The mean age of 8,248 patients in 25 studies was $54.0{\pm}15.1years$. The male/female ratio for oral cancer was 1.91. Tongue with average percentage of 29.9 was the most involved site. Regarding microscopic grade, 65.7% of cases were grade 1. SCCs, accounting for an average of 70.0%, was the most common among all types of oral cancer. In the majority of studies, smoking including cigarette, hookah, and tobacco consumption was found to be a risk factor. Conclusions: The epidemiological pattern of oral cancer in Iran is somewhat similar to that of other countries. Yet the information on hand in this field is limited and considering the role of epidemiological data we suggest conducting more accurate studies to catch data that is required for effective programs and interventions.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.6
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• pp.660-668
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• 2007

We investigated 248 patients who were diagnosed as malignant tumor in the department of Oral and maxillofacial Surgery of Kyungpook National University from 1999 to 2006, and following results were obtained. 1. Among 248 patients who have malignant tumor, 164 were men and 84 were women, which made the ratio of male to female 1.95:1. 2. The average age of oral cancer patients was 58.3. 3. As of the primary origin site, lower alveolus and gingiva were the greatest with 70 cases(28.2%), followed by tongue(l6.9%), upper alveolus and gingiva(14.9%), palate(13.7%), mouth floor(9.7%), buccal mucosa(4.8%), retromolar trigone(4.4%), Mx. & Mn. bone(3.2%) and lip(2.8%). 4. As of histologic distribution, squamous cell carcinoma was the greatest with 170 cases(68.6%), followed by sarcoma with 17 cases(6.9%), adenoid cystic carcinoma with 17 cases(6.9%), malignant lymphoma with 15 cases(6.0%), mucoepidermoid carcinoma with 13 cases(5.2%), metastatic carcinoma with 6 cases(2.4%) and malignant melanoma with 4 cases(1.6%). 5. Period between recognition of the symptom and the first visit to hospital was less than 3 months for 58.9% of the patients, and more than 3 months for 41% of the patients. 6. Investigation of whether the patients drink or smoke revealed that the number of non-smoking and non-drinking patients was 63 among 170 patients(37.0%) that were able to investigate. The number of patients who smoke only was 29(17.1%) and both drinking and smoking patients were 78(45.9%). 7. In clinical stage order, Stage IV(61.7%) was found th be the largest, followed by stage I(17.2%), stage II(13%) and stage III(7.8%). 8. The 5-year survival rate of the entire oral cancer patients appeared to be 57.7%. The survival rate was higher in younger group and women had higher survival rate but there was no statistical significance to this. In the aspect of stage, the survival rate was Stage I, Stage II, Stage IV and Stage III in decreasing order. The order according to T classification was the same. In N classification, patients with N0 had the highest survival rate and the survival rate decreased in the order of N1 and N2. Survival rate was especially low in patients with N2.

• Archives of Plastic Surgery
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• v.33 no.5
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• pp.557-562
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• 2006

Purpose: Advanced carcinoma of the tongue is a devastating disease which may cause severe speech or swallowing dysfunction. But, none to date has provided all of the complex functions of the tongue. The purpose of this study is to review our experiences with individuals who underwent glossectomy followed by reconstruction using free tissue transfer. Methods: Between February 1998 and February 2005, twenty-four patients underwent glossectomy followed by free tissue transfer reconstruction. The defects of tongue caused by partial or subtotal glossectomy were reconstructed by means of radial forearm or lateral thigh free flap with nerve innervation. Especially for the patients who underwent total glossectomy, we reconstructed deglutition muscles anatomically with nerve reinnervation, a procedure that allows the grafted muscle to maintain good tongue bulk without obvious atrophy. Results: Patients were reviewed to determine their functional outcome as it related to speech, deglutition, and aspiration. All patients achieved oral intake of a soft diet and acceptable speech. Conclusion: Although reconstruction following glossectomy using free tissue transfer is not ideal, this procedure is safe and reliable, and provides predictable results. A future challenge is the development of a surgical procedure for reconstruction of a tongue that maintains mobility and sensation using neurotized flaps.

• 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.