Agrin and Perlecan Mediate Tumorigenic Processes in Oral Squamous Cell Carcinoma

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Kawahara, Rebeca; Granato, Daniela C.; Carnielli, Carolina M.; Cervigne, Nilva K.; Oliveria, Carine E.; Martinez, César A. R.; Yokoo, Sami; Fonseca, Felipe P.; Lopes, Marcio; Santos-Silva, Alan R.; Graner, Edgard; Coletta, Ricardo D.; Leme, Adriana Franco Paes

2014-01-01

Oral squamous cell carcinoma is the most common type of cancer in the oral cavity, representing more than 90% of all oral cancers. The characterization of altered molecules in oral cancer is essential to understand molecular mechanisms underlying tumor progression as well as to contribute to cancer biomarker and therapeutic target discovery. Proteoglycans are key molecular effectors of cell surface and pericellular microenvironments, performing multiple functions in cancer. Two of the major basement membrane proteoglycans, agrin and perlecan, were investigated in this study regarding their role in oral cancer. Using real time quantitative PCR (qRT-PCR), we showed that agrin and perlecan are highly expressed in oral squamous cell carcinoma. Interestingly, cell lines originated from distinct sites showed different expression of agrin and perlecan. Enzymatically targeting chondroitin sulfate modification by chondroitinase, oral squamous carcinoma cell line had a reduced ability to adhere to extracellular matrix proteins and increased sensibility to cisplatin. Additionally, knockdown of agrin and perlecan promoted a decrease on cell migration and adhesion, and on resistance of cells to cisplatin. Our study showed, for the first time, a negative regulation on oral cancer-associated events by either targeting chondroitin sulfate content or agrin and perlecan levels. PMID:25506919

Correlation of Slug gene expression with lymph node metastasis and invasion molecule expression in oral squamous cell carcinoma tissue

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Shan-Ming Lu

2017-10-01

Full Text Available Objective: To study the correlation of Slug gene expression with lymph node metastasis and invasion molecule expression in oral squamous cell carcinoma tissue. Methods: Oral squamous cell carcinoma tissue surgical removed in Affiliated Stomatological Hospital of Nanjing Medical University between March 2015 and April 2017 was selected and divided into the oral squamous cell carcinoma tissue with neck lymph node metastasis and the oral squamous cell carcinoma tissues without lymph node metastasis according to the condition of lymph node metastasis. The expression of Slug, epithelial-mesenchymal transition molecules and invasion molecules in the oral squamous cell carcinoma tissue were detected. Results: Slug, N-cadherin, Vimentin, CD147, OPN, GRP78, SDF-1 and CXCR4 protein expression in oral squamous cell carcinoma tissue with neck lymph node metastasis were significantly higher than those in oral squamous cell carcinoma tissue without lymph node metastasis while E-cadherin, P120ctn and ZO-1 protein expression were significantly lower than those in oral squamous cell carcinoma tissue without lymph node metastasis; N-cadherin, Vimentin, CD147, OPN, GRP78, SDF-1 and CXCR4 protein expression in oral squamous cell carcinoma tissue with high Slug expression were significantly higher than those in oral squamous cell carcinoma tissue with low Slug expression while E-cadherin, P120ctn and ZO-1 protein expression were significantly lower than those in oral squamous cell carcinoma tissue with low Slug expression. Conclusion: The highly expressed Slug in oral squamous cell carcinoma tissue can promote the epithelial-mesenchymal transition and invasion of the cells to participate in the lymph node metastasis of tumor cells.

Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

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2017-11-15

Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Changes of serum prolactin level in patients with oral cavity squamous cell carcinoma

International Nuclear Information System (INIS)

Zheng Jian; Li Hairu; Chen Yaming; Tang Guihong; Xu Yalan

2004-01-01

To investigate the change of serum prolactin (PRL) level in patients with oral cavity squamous cell carcinoma, serum PRL level in 79 normal person and 68 cases of patient s was measured by RIA. The result showed that serum PRL level was significantly higher in 26 patients (38.2%, 26/68) than that in the control (P 0.05) between the sex and region of lesion. The above results indicated that proportion of patient with oral cavity squamous cell carcinoma was hyperprolactinaemia and the change of PRL was related to the development in oral cavity squamous cell carcinoma. (authors)

Novel Midkine Inhibitor iMDK Inhibits Tumor Growth and Angiogenesis in Oral Squamous Cell Carcinoma.

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Masui, Masanori; Okui, Tatsuo; Shimo, Tsuyoshi; Takabatake, Kiyofumi; Fukazawa, Takuya; Matsumoto, Kenichi; Kurio, Naito; Ibaragi, Soichiro; Naomoto, Yoshio; Nagatsuka, Hitoshi; Sasaki, Akira

2016-06-01

Midkine is a heparin-binding growth factor highly expressed in various human malignant tumors. However, its role in the growth of oral squamous cell carcinoma is not well understood. In this study, we analyzed the antitumor effect of a novel midkine inhibitor (iMDK) against oral squamous cell carcinoma. Administration of iMDK induced a robust antitumor response and suppressed cluster of differentiation 31 (CD31) expression in oral squamous cell carcinoma HSC-2 cells and SAS cells xenograft models. iMDK inhibited the proliferation of these cells dose-dependently, as well as the expression of midkine and phospho-extracellular signal-regulated kinase in HSC-2 and SAS cells. Moreover, iMDK significantly inhibited vascular endothelial growth factor and induced tube growth of human umbilical vein endothelial cells in a dose-dependent fashion. These findings suggest that midkine is critically involved in oral squamous cell carcinoma and iMDK can be effectively used for the treatment of oral squamous cell carcinoma. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.

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Sasahira, Tomonori; Kurihara, Miyako; Nishiguchi, Yukiko; Fujiwara, Rina; Kirita, Tadaaki; Kuniyasu, Hiroki

2016-08-01

Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.

Study of P21 Expression in Oral Lichen Planus and Oral Squamous Cell Carcinoma by Immunohistochemical Technique.

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Baghaei, Fahimeh; Shojaei, Setareh; Afshar-Moghaddam, Noushin; Zargaran, Massoumeh; Rastin, Verisheh; Nasr, Mohsen; Moghimbeigi, Abbas

2015-09-01

Lichen planus is a mucocutaneous disease that is relatively common in middle aged individuals. Some studies have shown that oral lichen planus has a potential to progress to squamous cell carcinoma.p21 is a cyclin-dependent kinase inhibitor that regulates the cell cycle, thus it acts as an inhibitor in cell proliferation. This study was aimed to evaluate and compare the immunostaining of p21 (as a proliferation inhibitory factor) in oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC). In this descriptive cross-sectional study, p21expression was investigated in 24 samples of oral lichen planus (OLP), 24 samples of oral squamous cell carcinoma (OSCC) and 24 samples of oral epithelial hyperplasia (OEH) by employing immunohistochemical staining. The mean percentage of p21-positive cells in OSCC (54.5±6.6) was significantly higher than that in OLP (32.8±6.08) and OEH (9.4±3.8). Moreover, OLP samples expressed p21 significantly higher than the OEH. Kruskal Wallis test revealed a statistically significant difference between the groups regarding the intensity of staining (plichen planus to SCC. Therefore, continuous follow-up periods for OLP are recommended for diagnosis of the malignant transformations in early stages.

Verrucoid Variant of Invasive Squamous Cell Carcinoma in Oral Submucous Fibrosis: A Clinicopathological Challenge.

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Ramani, Priya; Krithika, C; Ananthalakshmi, R; Singaram, Mamta; Jagdish, Praveena; Janardhanan, Sunitha; Jeevakarunyam, Sathiyajeeva

2016-11-04

Verrucous carcinoma (VC) is an exophytic, low-grade, well-differentiated variant of squamous cell carcinoma. It is described as a lesion appearing in the sixth or seventh decade of life that has minimal aggressive potential and, in long-standing cases, has been shown to transform into squamous cell carcinoma. Oral submucous fibrosis (OSMF) is a potentially malignant disorder, and about one-third of the affected population develop oral squamous cell carcinoma. The histopathological diagnosis of verrucous carcinoma is challenging, and the interpretation of early squamous cell carcinoma requires immense experience. Here we present a rare case of a 24-year-old male with OSMF transforming to verrucous carcinoma with invasive squamous cell carcinoma. Even though the case had a straightforward clinical diagnosis, the serial sectioning done for pathological diagnosis disclosed the squamous cell carcinoma.

Ubiquitin-specific protease 14 regulates cell proliferation and apoptosis in oral squamous cell carcinoma.

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Chen, Xiangyun; Wu, Jingjing; Chen, Yitian; Ye, Dongxia; Lei, Hu; Xu, Hanzhang; Yang, Li; Wu, Yingli; Gu, Wenli

2016-10-01

Ubiquitin-specific protease 14, a deubiquitinating enzyme, has been implicated in the tumorigenesis and progression of several cancers, but its role in oral squamous cell carcinoma remains to be elucidated. The aim of this study was to explore the expression pattern and roles of Ubiquitin-specific protease 14 in the occurrence and development of oral squamous cell carcinoma. Interestingly, Ubiquitin-specific protease 14 was overexpressed in oral cancer tissues and cell lines at both mRNA and protein levels. b-AP15, a specific inhibitor of Ubiquitin-specific protease 14, significantly inhibited the growth of cancer cells and increased cell apoptosis in a dose-dependent manner. Moreover, knockdown of Ubiquitin-specific protease 14 by shRNA significantly inhibited the proliferation and migration of cancer cells in vitro. Finally, using a xenograft mouse model of oral squamous cell carcinoma, knockdown of Ubiquitin-specific protease 14 markedly inhibited tumor growth and triggered the cancer cell apoptosis in vivo, supporting previous results. In conclusion, for the first time we have demonstrated the expression pattern of Ubiquitin-specific protease 14 in oral squamous cell carcinoma and verified a relationship with tumor growth and metastasis. These results may highlight new therapeutic strategies for tumor treatment, application of Ubiquitin-specific protease 14 selective inhibitor, such as b-AP15, or knockdown by shRNA. Collectively, Ubiquitin-specific protease 14 could be a potential therapeutic target for oral squamous cell carcinoma patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rapamycin enhances the anti-angiogenesis and anti-proliferation ability of YM155 in oral squamous cell carcinoma.

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Li, Kong-Liang; Wang, Yu-Fan; Qin, Jia-Ruo; Wang, Feng; Yang, Yong-Tao; Zheng, Li-Wu; Li, Ming-Hua; Kong, Jie; Zhang, Wei; Yang, Hong-Yu

2017-06-01

YM155, a small molecule inhibitor of survivin, has been studied in many tumors. It has been shown that YM155 inhibited oral squamous cell carcinoma through promoting apoptosis and autophagy and inhibiting proliferation. It was found that YM155 also inhibited the oral squamous cell carcinoma-mediated angiogenesis through the inactivation of the mammalian target of rapamycin pathway. Rapamycin, a mammalian target of rapamycin inhibitor, played an important role in the proliferation and angiogenesis of oral squamous cell carcinoma cell lines. In our study, cell proliferation assay, transwell assay, tube formation assay, and western blot assay were used to investigate the synergistic effect of rapamycin on YM155 in oral squamous cell carcinoma. Either in vitro or in vivo, rapamycin and YM155 exerted a synergistic effect on the inhibition of survivin and vascular endothelial growth factor through mammalian target of rapamycin pathway. Overall, our results revealed that low-dose rapamycin strongly promoted the sensitivity of oral squamous cell carcinoma cell lines to YM155.

Lymphatic mapping to tailor selective lymphadenectomy in squamous cell carcinoma of oral cavity

International Nuclear Information System (INIS)

Haq, M.E.U.; Warraich, R.A.; Abid, H.

2010-01-01

Objective: The purpose of this study was to determine the distribution of cervical lymph node metastases in the Squamous cell carcinoma of oral tongue and or floor of mouth; hence to improve the pretreatment evaluation of these patients. Study design: Descriptive study. Setting: Department of Oral and Maxillofacial Surgery, King Edward Medical University/ Mayo Hospital Lahore. From July 1, 2008 to December 31, 2009. Methods: This study was carried out on 50 consecutive patients who were having Squamous cell carcinoma of oral tongue and or floor of the mouth with T1 - T4 lesions. Results: Neck lymph node levels I and II were the most common sites of cervical lymph node metastases that was, 30%. Levels IV and V were involved very rarely. The overall metastases to cervical lymph node levels I - III combined was seen in 90% cases of oral tongue or floor of the mouth. Conclusion: The most common region for cervical lymph node metastases in Squamous Cell Carcinoma of oral tongue and floor of mouth is levels I - III in the ipsilateral neck, so based on pattern of metastases, supraomohyoid neck dissection for cN+ and functional neck dissection for cN+ necks are suggested. Key Words: Oral Squamous cell carcinoma (OSCC), cervical lymph node metastasis, cN+ (clinically lymph node negative), cN+ (clinically lymph node positive) (N1 - N/sub 3/), pN+ (pathologically lymph node metastases found), elective neck dissection, occult metastasis, radical neck dissection (RND). (author)

Lymphangiogenesis and angiogenesis in oral cavity and lower lip squamous cell carcinoma.

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Alaeddini, Mojgan; Etemad-Moghadam, Shahroo

2016-01-01

Tumors of the lip and oral cavity differ in various aspects; therefore a clarification of the distinctions among these sites may help to better understand the biologic behavior of neoplasms occurring in these locations. Considering that angiogenesis and lymphangiogenesis are two major elements that can influence various aspects of tumor biology, we aimed to compare these factors between squamous cell carcinoma of the lower lip and oral cavity. A total of 84 primary squamous cell carcinomas including 45 oral and 39 lower lip tumors were selected and immunohistochemically stained with monoclonal antibody against D2-40 and CD105. Mean microvessel density was assessed in tumoral tissue, while lymphatic vessel density was calculated in both neoplastic tissue and invasion front. Data were statistically analyzed using t-test and p-values of oral cavity and 27.54±20.8 in lower lip squamous cell carcinomas, with no significant difference (p=0.32). Mean lymphatic vessel density±standard deviation was 13.05±8.2 and 16.57±10.79 in of oral cavity and lower lip neoplastic tissue, respectively. The corresponding values were 9.94±5.59 and 12.50±7.8 in the invasive front. Significant differences were not observed in either of the lymphatic vessel density variables between the two sites. According to our results, it seems that the search for additional factors other than those related to the vasculature should continue, to help clarify the differences in biologic behavior between lower lip and oral cavity squamous cell carcinomas. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Cortactin is a prognostic marker for oral squamous cell carcinoma and its overexpression is involved in oral carcinogenesis.

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Liu, Yu-Ching; Ho, Heng-Chien; Lee, Miau-Rong; Yeh, Chung-Min; Tseng, Hsien-Chang; Lin, Yung-Chang; Chung, Jing-Gung

2017-03-01

EMS1 (chromosome eleven, band q13, mammary tumor and squamous cell carcinoma-associated gene 1) gene amplification and the concomitant cortactin overexpression have been reported to associate with poor prognosis and tumor metastasis. In this study, we examined cortactin expression by immunohistochemistry in human oral tumors and murine tongue tumors which were induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO). The immunostaining results show over- to moderate expression of cortactin in 85% (104/122) of oral squamous cell carcinoma (OSCC) tissues and in all 15 leukoplakia tissues examined. Further, statistical analysis indicates that cortactin overexpression appears to be a predictor for shorter survival and poorer prognosis in OSCC patients. In an animal model, cortactin is shown to upregulate in infiltrating squamous cell carcinoma, papilloma, and epithelia with squamous hyperplasia, indicating that cortactin induction is an early event during oral carcinogenesis. It is suggested that cortactin expression is mediated in the progression of pre-malignancy to papilloma, based on earlier cortactin induction in pre-malignancy preceding cyclin D1 in papilloma. In conclusion, cortactin overexpression is frequently observed in human OSCC and mouse tongue tumors. Thus, cortactin may have an important role in the development of oral tumors in human and mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 799-812, 2017. © 2016 Wiley Periodicals, Inc.

An overview on "cellular cannibalism" with special reference to oral squamous cell carcinoma.

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Jain, M

2015-12-01

Cellular cannibalism has been defined as a large cell engulfing a slightly smaller one within its cytoplasm. It has been described in various cancers like bladder cancer, breast cancer, lung cancer, gastric cancer, oral squamous cell carcinoma. Cellular cannibalism has been well correlated with anaplasia, tumor aggressiveness, grading and metastatic potential. Present review focuses on significance of cannibalism in relation to cancer with special emphasis on oral squamous cell carcinoma.

Isolated perifacial lymph node metastasis in oral squamous cell carcinoma with clinically node-negative neck.

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Agarwal, Sangeet Kumar; Arora, Sowrabh Kumar; Kumar, Gopal; Sarin, Deepak

2016-10-01

The incidence of occult perifacial nodal disease in oral cavity squamous cell carcinoma is not well reported. The purpose of this study was to evaluate the incidence of isolated perifacial lymph node metastasis in patients with oral squamous cell carcinoma with a clinically node-negative neck. The study will shed light on current controversies and will provide valuable clinical and pathological information in the practice of routine comprehensive removal of these lymph node pads in selective neck dissection in the node-negative neck. Prospective analysis. This study was started in August 2011 when intraoperatively we routinely separated the lymph node levels from the main specimen for evaluation of the metastatic rate to different lymph node levels in 231 patients of oral squamous cell cancer with a clinically node-negative neck. The current study demonstrated that 19 (8.22%) out of 231 patients showed ipsilateral isolated perifacial lymph node involvement. The incidence of isolated perifacial nodes did not differ significantly between the oral tongue (7.14%) and buccal mucosa (7.75%). Incidence was statistically significant in cases with lower age group (oral squamous cell carcinoma with a clinically node-negative neck. The incidence of isolated perifacial involvement is high in cases of buccal mucosal and tongue cancers. A meticulous dissection of the perifacial nodes seems prudent when treating the neck in oral cavity squamous cell carcinoma. 4 Laryngoscope, 126:2252-2256, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Genetic and epigenetic alterations of the blood group ABO gene in oral squamous cell carcinoma

DEFF Research Database (Denmark)

Gao, Shan; Worm, Jesper; Guldberg, Per

2004-01-01

Loss of histo-blood group A and B antigen expression is a frequent event in oral carcinomas and is associated with decreased activity of glycosyltransferases encoded by the ABO gene. We examined 30 oral squamous cell carcinomas for expression of A and B antigens and glycosyltransferases. We also....... Collectively, we have identified molecular events that may account for loss of A/B antigen expression in 67% of oral squamous cell carcinomas....

Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma.

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Mohanta, Simple; Siddappa, Gangotri; Valiyaveedan, Sindhu Govindan; Dodda Thimmasandra Ramanjanappa, Ravindra; Das, Debashish; Pandian, Ramanan; Khora, Samanta Sekhar; Kuriakose, Moni Abraham; Suresh, Amritha

2017-06-01

Differentiation is a major histological parameter determining tumor aggressiveness and prognosis of the patient; cancer stem cells with their slow dividing and undifferentiated nature might be one of the factors determining the same. This study aims to correlate cancer stem cell markers (CD44 and CD147) with tumor differentiation and evaluate their subsequent effect on prognosis. Immunohistochemical analysis in treatment naïve oral cancer patients (n = 53) indicated that the expression of CD147 was associated with poorly differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma (p squamous cell carcinoma and poorly differentiated squamous cell carcinoma patients were CD44 high /CD147 high as compared to only 10% of patients with well-differentiated squamous cell carcinoma. A three-way analysis indicated that differentiation correlated with recurrence and survival (p oral squamous cell carcinoma cell lines originating from different grades of oral cancer. Flowcytometry-based analysis indicated an increase in CD44 + /CD147 + cells in cell lines of poorly differentiated squamous cell carcinoma (94.35 ± 1.14%, p squamous cell carcinoma origin (93.49 ± 0.47%, p squamous cell carcinoma origin (23.12% ± 0.49%). Expression profiling indicated higher expression of cancer stem cell and epithelial-mesenchymal transition markers in SCC029B (poorly differentiated squamous cell carcinoma originated; p ≤ 0.001), which was further translated into increased spheroid formation, migration, and invasion (p squamous cell carcinoma origin. This study suggests that CD44 and CD147 together improve the prognostic efficacy of tumor differentiation; in vitro results further point out that these markers might be determinant of differentiation characteristics, imparting properties of increased self-renewal, migration, and invasion.

CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma

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Zhang, Heyu [Central Laboratory, Peking University School of Stomatology, Beijing (China); Nan, Xu [Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing (China); Li, Xuefen [Central Laboratory, Peking University School of Stomatology, Beijing (China); Chen, Yan; Zhang, Jianyun [Department of Oral Pathology, Peking University School of Stomatology, Beijing (China); Sun, Lisha [Central Laboratory, Peking University School of Stomatology, Beijing (China); Han, Wenlin [Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing (China); Li, Tiejun, E-mail: litiejun22@vip.sina.com [Department of Oral Pathology, Peking University School of Stomatology, Beijing (China)

2014-05-02

Highlights: • Down-regulation of CMTM5 expression in OSCC tissues was found. • The promoter methylation status of CMTM5 was measured. • CMTM5-v1 inhibited cell proliferation and migration and induced apoptosis. • CMTM5 might act as a putative tumor suppressor gene in OSCC. - Abstract: Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancies in the head and neck region. CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) has been recently implicated as a tumor suppressor gene in several cancer types. Herein, we examined the expression and function of CMTM5 in oral squamous cell carcinoma. CMTM5 was down-regulated in oral squamous cell lines and tumor samples from patients with promoter methylation. Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored CMTM5 expression. In the OSCC cell lines CAL27 and GNM, the ectopic expression of CMTM5-v1 strongly inhibited cell proliferation and migration and induced apoptosis. In addition, CMTM5-v1 inhibited tumor formation in vivo. Therefore, CMTM5 might act as a putative tumor suppressor gene through promoter methylation in oral squamous cell carcinoma.

CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Zhang, Heyu; Nan, Xu; Li, Xuefen; Chen, Yan; Zhang, Jianyun; Sun, Lisha; Han, Wenlin; Li, Tiejun

2014-01-01

Highlights: • Down-regulation of CMTM5 expression in OSCC tissues was found. • The promoter methylation status of CMTM5 was measured. • CMTM5-v1 inhibited cell proliferation and migration and induced apoptosis. • CMTM5 might act as a putative tumor suppressor gene in OSCC. - Abstract: Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancies in the head and neck region. CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) has been recently implicated as a tumor suppressor gene in several cancer types. Herein, we examined the expression and function of CMTM5 in oral squamous cell carcinoma. CMTM5 was down-regulated in oral squamous cell lines and tumor samples from patients with promoter methylation. Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored CMTM5 expression. In the OSCC cell lines CAL27 and GNM, the ectopic expression of CMTM5-v1 strongly inhibited cell proliferation and migration and induced apoptosis. In addition, CMTM5-v1 inhibited tumor formation in vivo. Therefore, CMTM5 might act as a putative tumor suppressor gene through promoter methylation in oral squamous cell carcinoma

Techniques for early diagnosis of oral squamous cell carcinoma: Systematic review

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Carreras-Torras, Clàudia

2015-01-01

Background and objectives The diagnosis of early oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) is of paramount clinical importance given the mortality rate of late stage disease. The aim of this study is to review the literature to assess the current situation and progress in this area. Material and Methods A search in Cochrane and PubMed (January 2006 to December 2013) has been used with the key words “squamous cell carcinoma”, “early diagnosis” “oral cavity”, “Potentially Malignant Disorders” y “premalignant lesions”. The inclusion criteria were the use of techniques for early diagnosis of OSCC and OPMD, 7 years aged articles and publications written in English, French or Spanish. The exclusion criteria were case reports and studies in other languages. Results Out of the 89 studies obtained initially from the search 60 articles were selected to be included in the systematic review: 1 metaanalysis, 17 systematic reviews, 35 prospective studies, 5 retrospective studies, 1 consensus and 1 semi-structured interviews. Conclusions The best diagnostic technique is that which we have sufficient experience and training. Definitely tissue biopsy and histopathological examination should remain the gold standard for oral cancer diagnose. In this systematic review it has not been found sufficient scientific evidence on the majority of proposed techniques for early diagnosis of OSCC, therefore more extensive and exhaustive studies are needed. Key words: Squamous cell carcinoma, early diagnosis, oral cavity, potentially malignant disorders, premalignant lesions. PMID:25662554

Role of atypical chemokine receptor ACKR2 in experimental oral squamous cell carcinogenesis.

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da Silva, Janine Mayra; Dos Santos, Tálita Pollyanna Moreira; Saraiva, Adriana Machado; Fernandes de Oliveira, Ana Laura; Garlet, Gustavo Pompermaier; Batista, Aline Carvalho; de Mesquita, Ricardo Alves; Russo, Remo Castro; da Silva, Tarcília Aparecida

2018-03-14

Chemokines and chemokine receptors are critical in oral tumourigenesis. The atypical chemokine receptor ACKR2 is a scavenger of CC chemokines controlling the availability of these molecules at tumour sites, but the role of ACKR2 in the context of oral carcinogenesis is unexplored. In this study, wild-type (WT) and ACKR2 deficient mice (ACKR2 -/- ) were treated with chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) for induction of oral carcinogenesis. Tongues were collected for macro and microscopic analysis and to evaluate the expression of ACKRs, CC chemokines and its receptors, inflammatory cytokines, angiogenic factors, adhesion molecules and extracellular matrix components. An increased expression of ACKR2 in squamous cell carcinoma (SCC) lesions of 4NQO-treated WT mice was observed. No significant differences were seen in the ACKR1, ACKR3 and ACKR4 mRNA expression comparing SCC lesions from WT and ACKR2 -/- treated mice. Significantly higher expression of CCL2, IL-6 and IL-17 was detected in ACKR2 -/- treated mice. In contrast, the expression of other CC-chemokines, and receptors, angiogenic factors, adhesion molecules and extracellular matrix components were similarly increased in SCC lesions of both groups. Clinical and histopathological analysis revealed no differences in inflammatory cell recruitment and in the SCC incidence comparing WT and ACKR2 -/- treated mice. The results suggest that ACKR2 expression regulates inflammation in tumour-microenvironment but the absence of ACKR2 does not impact chemically-induced oral carcinogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prognostic potential of n-cadherin in oral squamous cell carcinoma via immunohistochemical methods

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Chandolia, B.; Arora, M.; Rajliwal, P.

2017-01-01

To assess the prognostic potential for N-cadherin in oral squamous cell carcinoma and oral epithelial dysplasia. Study Design: A cross-sectional study, analytical study. Place and Duration of Study: Maharishi Markandeshwar College of Dental Science Research (MMCDSR), Ambala, India, from 2011 to 2014. Methodology: Immunohistochemistry was used to observe the N-cadherin expression in 100 cases having epithelium with normal oral mucosa, oral epithelial dysplastic lesions and oral squamous cell carcinoma (OSCC). For statistical significance, SPSS 13.0 was used to calculate the data by Mann-Whitney and Kruskal-Wallis tests. Results: In OSCC, N-cadherin expression was more evident than in oral epithelial dysplasia followed by the normal oral epithelium that did not show any dysplastic changes (p=0.001). Conversely, N-cadherin expression was not significant among the histological grade of OSCC. Conclusion: N-cadherin can be used as a potential biomarker for early diagnosis of OSCC. However, the N-cadherin expression did not show any correlation with the histological grade of OSCC. (author)

Prognostic Potential of N-Cadherin in Oral Squamous Cell Carcinoma via Immunohistochemical Methods.

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Chandolia, Betina; Rajliwal, Jai Parkash; Bajpai, Manas; Arora, Manika

2017-08-01

To assess the prognostic potential for N-cadherin in oral squamous cell carcinoma and oral epithelial dysplasia. Across-sectional study, analytical study. Maharishi Markandeshwar College of Dental Science Research (MMCDSR), Ambala, India, from 2011 to 2014. Immunohistochemistry was used to observe the N-cadherin expression in 100 cases having epithelium with normal oral mucosa, oral epithelial dysplastic lesions and oral squamous cell carcinoma (OSCC). For statistical significance, SPSS 13.0 was used to calculate the data by Mann-Whitney and Kruskal-Wallis tests. In OSCC, N-cadherin expression was more evident than in oral epithelial dysplasia followed by the normal oral epithelium that did not show any dysplastic changes (p=0.001). Conversely, N-cadherin expression was not significant among the histological grade of OSCC. N-cadherin can be used as a potential biomarker for early diagnosis of OSCC. However, the N-cadherin expression did not show any correlation with the histological grade of OSCC.

Detection of the E7 transform gene of human papilloma virus type 16 in human oral squamous cell carcinoma.

Science.gov (United States)

Wang, J; Li, J; Huang, H; Fu, Y

1998-12-01

To determine, with the use of polymerase chain reaction, the prevalence of human papillomavirus (HPV) 16 in 30 patients with primary oral squamous cell carcinoma (OSCC) and 30 healthy control patients. DNA was extracted from freshly frozen tumor tissues of 30 patients with primary oral squamous cell carcinoma and from the oral mucosa of 30 controls. A pair of specific primers of the E7 early gene of HPV 16 were designed. PCR products were run by 1.5% agarose gel and the results of electrophoresis were photographed. HPV 16 was detected in 36.7% (11/30) of oral squamous cell carcinoma patients and 11.1% (4/30) of controls. HPV 16 has a significant association with oral squamous cell carcinoma. However, the role HPV 16 plays in the tumorigenesis of oral cancer and its clinical significance remain to be investigated.

Salvage surgery for radiation failure in oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma

International Nuclear Information System (INIS)

Suzuki, Masahiro; Terada, Akihiro; Ogawa, Tetsuya; Suzuki, Hidenori; Hasegawa, Yasuhisa

2007-01-01

Few reports have covered salvage surgery after radiotherapy, especially with chemotherapy for oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma. The feasibility of salvage surgery is unclear. We analyzed postoperative complications and prognosis after salvage surgery for local recurrence after definitive radiotherapy. Subjects were 37 patients with oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma treated from 1994 to 2003. Of these, 14 (37.8%) had postoperative complications. The complication rate was significantly high in the reconstructive operation group (p=0.031) and the chemotherapy group (p=0.049). The 5-year overall survival rate after salvage surgery was 70.7%. Although there was no significant improvement, the prognosis was good in early-stage groups with primary tumors. We found that salvage surgery after definitive radiotherapy was effective for recurrent oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma. We stress the need to pay attention to postoperative complications in reconstructive operation and chemotherapy groups. (author)

Textural pattern classification for oral squamous cell carcinoma.

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Rahman, T Y; Mahanta, L B; Chakraborty, C; DAS, A K; Sarma, J D

2018-01-01

Despite being an area of cancer with highest worldwide incidence, oral cancer yet remains to be widely researched. Studies on computer-aided analysis of pathological slides of oral cancer contribute a lot to the diagnosis and treatment of the disease. Some researches in this direction have been carried out on oral submucous fibrosis. In this work an approach for analysing abnormality based on textural features present in squamous cell carcinoma histological slides have been considered. Histogram and grey-level co-occurrence matrix approaches for extraction of textural features from biopsy images with normal and malignant cells are used here. Further, we have used linear support vector machine classifier for automated diagnosis of the oral cancer, which gives 100% accuracy. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma.

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Sobrinho Santos, Eliane Macedo; Guimarães, Talita Antunes; Santos, Hércules Otacílio; Cangussu, Lilian Mendes Borborema; de Jesus, Sabrina Ferreira; Fraga, Carlos Alberto de Carvalho; Cardoso, Claudio Marcelo; Santos, Sérgio Henrique Souza; de Paula, Alfredo Maurício Batista; Gomez, Ricardo Santiago; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

2017-05-01

Leptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma. Expression of genes possibly linked to the leptin pathway was assessed in leptin-treated oral squamous cell carcinoma cells and also in tissue samples of oral squamous cell carcinoma and oral mucosa, including leptin, leptin receptor, hypoxia-inducible factor 1-alpha, E-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9, Col1A1, Ki67, and mir-210. Leptin treatment favored higher rates of cell proliferation and migration, and reduced apoptosis. Accordingly, leptin-treated oral squamous cell carcinoma cells show decreased messenger RNA caspase-3 expression, and increased levels of E-cadherin, Col1A1, matrix metalloproteinase-2, matrix metalloproteinase-9, and mir-210. In tissue samples, hypoxia-inducible factor 1-alpha messenger RNA and protein expression of leptin and leptin receptor were high in oral squamous cell carcinoma cases. Serum leptin levels were increased in first clinical stages of the disease. In animal model, oral squamous cell carcinoma-induced mice show higher leptin receptor expression, and serum leptin level was increased in dysplasia group. Our findings suggest that leptin seems to exert an effect on oral squamous cell carcinoma cells behavior and also on molecular markers related to cell proliferation, migration, and tumor angiogenesis.

Is Human Oxoguanine Glycosylase 1 Genetic Variant Successful Even on Oral Squamous Cell Carcinoma?

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Aydemir, Levent; Bireller, Elif Sinem; Avci, Hakan; Boy Metin, Zeynep; Deger, Kemal; Unur, Meral; Cakmakoglu, Bedia

2017-01-01

Oral squamous cell carcinoma (OSCC) is one of the most widespread cancer types that arise from different sites of oral cavity and has a 5-year survival rate. This study is aimed at investigating the human oxoguanine glycosylase 1 (hOGG1)-Ser326Cys and APE-Asp148Glu polymorphisms of DNA repair genes in OSCC. We investigated the hOGG1-Ser326Cys and APE-Asp148Glu polymorphisms of DNA repair genes in the oral cavity. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism analysis based on 132 patients who were diagnosed as having OSCC and 160 healthy subjects. Individuals with the genotype hOGG1-Ser326Cys, Cys allele carriers, were found significantly more frequently in the patient group compared to the control group as increase in risk (p oral squamous cancer. In view of our results, further studies including expression levels are required in which hOGG1-Ser326Cys should be investigated as molecular biomarkers for the early prediction of squamous cell carcinoma. © 2017 S. Karger AG, Basel.

Immunohistochemical study of p21 and Bcl-2 in leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma.

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Sutariya, Rakesh V; Manjunatha, Bhari Sharanesha

2016-11-01

Oral Squamous cell carcinoma (OSCC) results from genetic damage, leading to uncontrolled cell proliferation of damaged cells and the cell death. In the course of its progression, visible changes are taking place at the cellular level (atypical) and the resultant at the tissue level (epithelial dysplasia). The Aim of the present study was to evaluate and compare the expressions of intensity of p21 and Bcl-2 in Leukoplakia, oralsubmucous fibrosis (OSMF) and oral squamous cell carcinoma. Total 60 cases, 30 cases of oral squamous cell carcinoma, 15 cases of oral submucous fibrosis and 15 cases of Leukoplakia were evaluated immunohistochemically for p21 and Bcl-2 expression. p21 showed positive expression in 13 (86.67%) cases out of 15 cases of OSMF, 12 (80%) cases of leukoplakia out of 15 cases and 24 (80%) cases out of 30 cases of OSCC. The Bcl-2 expression was positive in 13 (86.67%) cases of OSMF, all cases of Leukoplakia and 25 (83.33%) cases of OSCC. No statistical significance was noted in the expression of p21 and Bcl-2 positive expression between OSMF, Leukoplakia and OSCC. Statistical analysis for comparison of intensity of p21 expression in different grades of OSCC showed no significance. Statistical significance difference was found between the expressions of Bcl-2 in moderately and poorly differentiated SCC. The intensity of p21 and Bcl-2 expressions in different grades of OSCC indicates a key role in progression of oral neoplasia.

Gallic acid modulates phenotypic behavior and gene expression in oral squamous cell carcinoma cells by interfering with leptin pathway.

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Santos, Eliane Macedo Sobrinho; da Rocha, Rogério Gonçalves; Santos, Hércules Otacílio; Guimarães, Talita Antunes; de Carvalho Fraga, Carlos Alberto; da Silveira, Luiz Henrique; Batista, Paulo Ricardo; de Oliveira, Paulo Sérgio Lopes; Melo, Geraldo Aclécio; Santos, Sérgio Henrique; de Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

2018-01-01

Gallic acid is a polyphenolic compost appointed to interfere with neoplastic cells behavior. Evidence suggests an important role of leptin in carcinogenesis pathways, inducing a proliferative phenotype. We investigated the potential of gallic acid to modulate leptin-induced cell proliferation and migration of oral squamous cell carcinoma cell lines. The gallic acid effect on leptin secretion by oral squamous cell carcinoma cells, as well as the underlying molecular mechanisms, was also assessed. For this, we performed proliferation, migration, immunocytochemical and qPCR assays. The expression levels of cell migration-related genes (MMP2, MMP9, Col1A1, and E-cadherin), angiogenesis (HIF-1α, mir210), leptin signaling (LepR, p44/42 MAPK), apoptosis (casp-3), and secreted leptin levels by oral squamous cell carcinoma cells were also measured. Gallic acid decreased proliferation and migration of leptin-treated oral squamous cell carcinoma cells, and reduced mRNA expression of MMP2, MMP9, Col1A1, mir210, but did not change HIF-1α. Gallic acid decreased levels of leptin secreted by oral squamous cell carcinoma cells, accordingly with downregulation of p44/42 MAPK expression. Thus, gallic acid appears to break down neoplastic phenotype of oral squamous cell carcinoma cells by interfering with leptin pathway. Copyright © 2017 Elsevier GmbH. All rights reserved.

Oral squamous cell carcinoma in the background of oral submucous fibrosis is a distinct clinicopathological entity with better prognosis.

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Gadbail, Amol Ramchandra; Chaudhary, Minal; Gawande, Madhuri; Hande, Alka; Sarode, Sachin; Tekade, Satyajit Ashok; Korde, Sheetal; Zade, Prajakta; Bhowate, Rahul; Borle, Rajiv; Patil, Swati

2017-07-01

The aim of this study was to compare the clinicopathological features of oral squamous cell carcinoma in the background of oral submucous fibrosis (OSCC-OSMF) and oral squamous cell carcinoma (OSCC). A total of 217 cases of OSCC were retrieved from achieves for the analysis. OSCC-OSMF cases were segregated on the basis of history and clinicopathological parameters. The study included 217 patients of which 112 had OSCC and 105 OSCC-OSMF. OSCC-OSMFs were younger compared with OSCC. Overall oral cancer was noted predominantly in males compared to females. The number of OSCC-OSMF was more in clinical TNM stage I and stage II as compared to OSCC, whereas the number of OSCC was more in stage III and stage IV compared to OSCC-OSMF. Histological presentation of well-differentiated squamous cell carcinoma was significantly more in OSCC-OSMF compared to OSCC, whereas moderately differentiated squamous cell carcinoma was significantly more in OSCC compared to OSCC-OSMF. Regional lymph node metastasis was significantly higher in OSCC compared to OSCC-OSMF. Three-year disease-free survival rate was significantly higher in OSCC-OSMF compared to OSCC. The OSCC-OSMF was found to be a clinicopathologically distinct entity with a better grade of tumor differentiation, less incidence of nodal metastases, and early detection (early clinical TNM stage) compared to OSCC. All these factors probably contribute to a better prognosis and increased 3-year disease-free survival in OSCC-OSMF patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Prevalence of human papillomavirus infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx].

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Villagómez-Ortíz, Vicente José; Paz-Delgadillo, Diana Estela; Marino-Martínez, Iván; Ceseñas-Falcón, Luis Ángel; Sandoval-de la Fuente, Anabel; Reyes-Escobedo, Alfonso

2016-01-01

Cancer of the head and neck comprises a group of neoplasms that share a similar anatomical origin. Most originate from the epithelium of the aerodigestive tract and 90% correspond to squamous cell carcinoma. In the last 15 years, an increase in the incidence of squamous cell carcinoma induced by human papillomavirus (HPV) has been seen, mainly types 16 and 18, which are the most frequent found in cancers of the oral cavity and oropharynx, and types 6 and 11 in laryngeal cancer. There are reports in the literature that show HPV as the leading cause of oropharyngeal squamous cell carcinoma. Determine the prevalence of infection with high-risk HPV in patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx and larynx. An observational, cross-sectional, descriptive, unblinded study was performed. Prevalence of HPV infection was determined by polymerase chain reaction (PCR) in DNA samples from tumour tissue of patients with squamous cell carcinoma of the oral cavity, oropharynx and larynx. Typing was subsequently performed in HPV positive samples in order to detect types 18, 16, 11 and 6, using custom primers. A total of 45 patients were included. The association between laryngeal squamous cell carcinoma and HPV was established in two patients, which represented an overall prevalence of 4.4% in our population, and 10% for laringeal tumours. There is a low prevalence of HPV infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx, in our population. Prospective studies on younger patients could provide more information. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Expression of hypoxia-induced factor-1 alpha in early-stage and in metastatic oral squamous cell carcinoma.

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Ribeiro, Maisa; Teixeira, Sarah R; Azevedo, Monarko N; Fraga, Ailton C; Gontijo, Antônio Pm; Vêncio, Eneida F

2017-04-01

To investigate hypoxia-induced factor-1 alpha expression in distinct oral squamous cell carcinoma subtypes and topographies and correlate with clinicopathological data. Hypoxia-induced factor-1 alpha expression was assessed by immunohistochemistry in 93 cases of OSCC. Clinical and histopathological data were reviewed from medical records. Hypoxia-induced factor-1 alpha status was distinct according to tumor location, subtype and topography affect. In superficial oral squamous cell carcinomas, most tumor cells overexpressed hypoxia-induced factor-1 alpha, whereas hypoxia-induced factor-1 alpha was restricted to the intratumoral region in conventional squamous cell carcinomas. All basaloid squamous cell carcinomas exhibited downregulation of hypoxia-induced factor-1 alpha. Interestingly, metastatic lymph nodes (91.7%, p = 0.001) and the intratumoral regions of corresponding primary tumors (58.3%, p = 0.142) showed hypoxia-induced factor-1 alpha-positive tumor cells. Overall survival was poor in patients with metastatic lymph nodes. Hypoxia-induced factor-1 alpha has distinct expression patterns in different oral squamous cell carcinoma subtypes and topographies, suggesting that low oxygen tension promotes the growth pattern of superficial and conventional squamous cell carcinoma, but not basaloid squamous cell carcinoma. Indeed, a hypoxic environment may facilitate regional metastasis, making it a useful diagnostic and prognostic marker in primary tumors.

Immunoreactive transforming growth factor alpha and epidermal growth factor in oral squamous cell carcinomas

DEFF Research Database (Denmark)

Therkildsen, M H; Poulsen, Steen Seier; Bretlau, P

1993-01-01

Forty oral squamous cell carcinomas have been investigated immunohistochemically for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF). The same cases were recently characterized for the expression of EGF-receptors. TGF-alpha was detected...... previous results confirms the existence of TGF-alpha, EGF, and EGF-receptors in the majority of oral squamous cell carcinomas and their metastases......., the cells above the basal cell layer were positive for both TGF-alpha and EGF. The same staining pattern was observed in oral mucosa obtained from healthy persons. In moderately to well differentiated carcinomas, the immunoreactivity was mainly confined to the cytologically more differentiated cells, thus...

Expression and associations of TRAF1, BMI-1, ALDH1, and Lin28B in oral squamous cell carcinoma.

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Wu, Tian-Fu; Li, Yi-Cun; Ma, Si-Rui; Bing-Liu; Zhang, Wen-Feng; Sun, Zhi-Jun

2017-04-01

Tumor necrosis factor receptor-associated factor 1, an adaptor protein of tumor necrosis factor 2, is involved in classical nuclear factor (NF)-κB activation and lymphocyte recruitment. However, less is known about the expression and association of tumor necrosis factor receptor-associated factor 1 with cancer stem cell markers in oral squamous cell carcinoma. This study aimed to investigate the expression of tumor necrosis factor receptor-associated factor 1 and stem cell characteristic markers (lin28 homolog B, B cell-specific Moloney murine leukemia virus integration site 1, and aldehyde dehydrogenase 1) in oral squamous cell carcinoma and analyze their relations. Paraffin-embedded tissues of 78 oral squamous cell carcinomas, 39 normal oral mucosa, and 12 oral dysplasia tissues were employed in tissue microarrays, and the expression of tumor necrosis factor receptor-associated factor 1, B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B was measured by immunohistostaining and digital pathological analysis. The expression of tumor necrosis factor receptor-associated factor 1 was higher in the oral squamous cell carcinoma group as compared with the expression in the oral mucosa (p oral dysplasia (p oral squamous cell carcinoma. The patient survival rate was lower in the highly expressed tumor necrosis factor receptor-associated factor 1 group, although the difference was not significant. The clustering analysis showed that tumor necrosis factor receptor-associated factor 1 was most related to aldehyde dehydrogenase 1. These findings suggest that tumor necrosis factor receptor-associated factor 1 has potential direct/indirect regulations with the cancer stem cell markers in oral squamous cell carcinoma, which may help in further analysis of the cancer stem cell characteristics.

Interleukin-37 expression and its potential role in oral leukoplakia and oral squamous cell carcinoma.

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Lin, Lin; Wang, Jiayi; Liu, Dongjuan; Liu, Sai; Xu, Hao; Ji, Ning; Zhou, Min; Zeng, Xin; Zhang, Dunfang; Li, Jing; Chen, Qianming

2016-05-26

Interleukin 37 (IL-37) has been reported to play a significant role in innate immune response and to be involved in several kinds of cancers. However, the investigation of association between IL-37 and oral mucosa carcinogenesis hasn't been clearly established. The aim of the study was to assess IL-37 expression and explore its role in oral mucosa carcinogenesis. The expression of IL-37 increased from normal control (NC) to Oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). Moreover, statistically highly significant difference was present between scores of OLK with and without mild/moderate dysplasia (P oral mucosa carcinogenesis. Overall, IL-37 can be used as a biomarker for early oral tumorigenesis and for malignant transformation risk assessment of premalignant lesions.

Silencing of long non-coding RNA CCAT2 depressed malignancy of oral squamous cell carcinoma via Wnt/β-catenin pathway.

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Ma, Yuji; Hu, Xuanhao; Shang, Chao; Zhong, Ming; Guo, Yan

2017-07-01

Oral squamous cell carcinoma is a common and lethal malignancy affecting the head and neck region. CCAT2 (colon cancer-associated transcript 2) gene is affiliated with long non-coding RNAs, which are often found to have important regulatory roles in cancers. This study aims to assess the expression and clinical significance of CCAT2 gene, identify its malignant biological behaviors, and explore the possible mechanisms in oral squamous cell carcinoma. CCAT2 expression was detected by quantitative real-time polymerase chain reaction, and its relationship with clinical factors was assayed using the Kaplan-Meier survival curve. The biological behaviors of CCAT2 and its potential mechanisms in oral squamous cell carcinoma were explored by the combined use of CCAT2 knockdown technology and the Wnt/β-catenin pathway agonist lithium chloride (LiCl). Our results showed that CCAT2 functioning as a potential oncogene was upregulated in oral squamous cell carcinoma. CCAT2 with high expression level was correlated with poor differentiation, higher T stage, and clinical stage, which made CCAT2 to be a prognostic biomarker in oral squamous cell carcinoma. LiCl-activated Wnt/β-catenin signaling pathway could partly restore the CCAT2-mediated malignant biological behaviors of oral squamous cell carcinoma cells by suppressing β-catenin, CCND1, and MYC and activating glycogen synthase kinase 3 beta expression. These findings might assist in the discovery of novel potential diagnostic and therapeutic target for oral squamous cell carcinoma, thereby improve the effects of clinical treatment in patients.

Fluorescence detection of oral squamous cell carcinoma using Hyperflav

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Melnik, Ivan S.; Dets, Sergiy M.; Rawicz, Andrew H.; Zhang, Lewei

2000-05-01

A novel hypericin-based drug HyperflavTM has been evaluated for light-induced fluorescence detection of oral cancer. Squamous cell carcinoma was induced with carcinogenic agent in right pouches of forty hamsters (20/20 males/females). Solution of HyperflavTM was sprinkled into stomach with a single dose 0.2 - 4 mg of pure hypericin per kg b.w. and 4 - 8 hours before fluorescence analysis. In two animal groups with cancer symptoms the autofluorescence and hypericin-induced fluorescence were taken under 442 nm excitation. The buccal mucosa and adjacent areas were measured fiberoptically in-vivo and in-vitro using orange/green ratio (610/540). The in-vivo fluorescence imaging of malignant areas was conducted to assist the biopsy guidance and to compare with white-light images. Histological and morphological analyses were performed from biopsies. Oral squamous cell carcinoma in its early stage demonstrated specific higher 610/540 ratio for 37 tested hamsters. Advanced state involved another higher fluorescence maximum around 640 nm that in our opinion caused by strong porphyrin-induced native fluorescence. Such deformation of fluorescence spectra may lead to inadequate perception of diseased tissue area. To avoid this problem the autofluorescence spectra & images were added. HyperflavTM application is promising for demarcation of early oral cancer when combined with autofluorescence measurements.

Staging of Cervical Lymph Nodes in Oral Squamous Cell Carcinoma

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Norling, Rikke; Buron, Birgitte Marie Due; Therkildsen, Marianne Hamilton

2014-01-01

INTRODUCTION: Clinical staging of patients with oral squamous cell carcinoma (OSCC) is crucial for the choice of treatment. Computed tomography (CT) and/or magnetic resonance imaging (MRI) are typically recommended and used for staging of the cervical lymph nodes (LNs). Although ultrasonography (US...

MicroRNA-137 promoter methylation in oral lichen planus and oral squamous cell carcinoma

DEFF Research Database (Denmark)

Dang, Jun; Bian, Yong-qian; Sun, Jian-yong

2013-01-01

and patients with oral squamous cell carcinoma (OSCC). A total of 20 OLP and 12 patients with OSCC as well as 10 healthy subjects were subjected to miR-137 promoter methylation analysis using methylation-specific PCR (MSP). To address the malignancy prediction potential from miR-137 promoter methylation status...

MicroRNAs in Head and Neck Squamous Cell Carcinoma (HNSCC) and Oral Squamous Cell Carcinoma (OSCC)

International Nuclear Information System (INIS)

Shiiba, Masashi; Uzawa, Katsuhiro; Tanzawa, Hideki

2010-01-01

MicroRNAs (miRNAs) are small, noncoding RNAs which regulate cell differentiation, proliferation, development, cell cycle, and apoptosis. Expression profiling of miRNAs has been performed and the data show that some miRNAs are upregulated or downregulated in cancer. Several studies suggest that the expression profiles of miRNAs are associated with clinical outcomes. However, the set of miRNAs with altered expressing differs depending on the type of cancer, suggesting that it is important to understand which miRNAs are related to which cancers. Therefore, this review aimed to discuss potentially crucial miRNAs in head and neck squamous cell carcinoma (HNSCC) and oral squamous cell carcinoma (OSCC)

Glutaminolysis and carcinogenesis of oral squamous cell carcinoma.

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Cetindis, Marcel; Biegner, Thorsten; Munz, Adelheid; Teriete, Peter; Reinert, Siegmar; Grimm, Martin

2016-02-01

Glutaminolysis is a crucial factor for tumor metabolism in the carcinogenesis of several tumors but has not been clarified for oral squamous cell carcinoma (OSCC) yet. Expression of glutaminolysis-related solute carrier family 1, member 5 (SLC1A5)/neutral amino acid transporter (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLDH) was analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry. SLC1A5/ASCT2 and GLS were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue, while GLDH was weakly detected. Compared with SIN I-III SLC1A5/ASCT2 and GLS expression were significantly increased in OSCC. GLDH expression did not significantly differ from SIN I-III compared with OSCC. This study shows the first evidence of glutaminolysis-related SLC1A5/ASCT2, GLS, and GLDH expression in OSCC. The very weak GLDH expression indicates that glutamine metabolism is rather related to nucleotide or protein/hexosamine biosynthesis or to the function as an antioxidant (glutathione) than to energy production or generation of lactate through entering the tricarboxylic acid cycle. Overcoming glutaminolysis by targeting c-Myc oncogene (e.g. by natural compounds) and thereby cross-activation of mammalian target of rapamycin complex 1 or SLC1A5/ASCT2, GLS inhibitors may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies.

Evaluation of Podoplanin in Oral Leukoplakia and Oral Squamous Cell Carcinoma

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Ashok Patil

2015-01-01

Full Text Available Background. Recent studies have demonstrated that podoplanin was expressed in some dysplastic lesions adjacent to primary oral cancers suggesting that podoplanin expression may occur in early oral tumorigenesis and lymphangiogenesis and therefore is related to tumor growth. The purpose of this study is to determine the role of podoplanin as a biomarker for cancer risk assessment in oral leukoplakia and correlation of podoplanin expression with grades of oral squamous cell carcinoma (OSCC. Materials and Methods. In the present retrospective study, podoplanin expression was investigated immunohistochemically in 40 patients each of oral leukoplakia and OSCC. The scores were analyzed statistically using one-way ANOVA test followed by Tukey HSD. Results. By applying one-way ANOVA test, there was a highly significant increase of the podoplanin expression from mild to severe dysplasia and from well to poorly differentiated OSCC (P<0.01. Statistically highly significant difference was present between scores of mild to moderate dysplasia, moderate to severe dysplasia, well to poorly differentiated OSCC, and moderately to poorly differentiated OSCC (Tukey HSD test, P<0.01. Conclusion. Podoplanin can be used as a biomarker for early oral tumorigenesis and for malignant transformation risk assessment of premalignant lesions and as a tumor progression biomarker for advanced grades of OSCC.

Oral Rigosertib for Squamous Cell Carcinoma

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2017-06-22

Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

Ultra-deep sequencing reveals the subclonal structure and genomic evolution of oral squamous cell carcinoma

DEFF Research Database (Denmark)

Tabatabaeifar, Siavosh; Thomassen, Mads; Larsen, Martin Jakob

Background: Oral squamous cell carcinoma (OSCC), a subgroup of head and neck squamous cell carcinoma (HNSCC), is primarily caused by alcohol consumption and tobacco use. Recent DNA sequencing studies suggests that HNSCC are very heterogeneous between patients; however the intra-patient subclonal...

Prevalence and relationship of human papilloma virus type 16 and type 18 with oral squamous cell carcinoma and oral leukoplakia in fresh scrappings: a PCR study.

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Mathew, Asok; Mody, R N; Patait, Mahendra R; Razooki, Ali A; Varghese, Nisha T; Saraf, Kedar

2011-05-01

It has been always an area of diffuse clarity when you study malignancy and its pathogenesis. Recently, it has invited lot of interest among the researchers about the possibility of role of viruses in the initiation of carcinogenesis. Recent advances in the field of molecular biology and biotechnology have solved some problems with regard to pathogenesis. Human papilloma virus (HPV) and its role in the initiation of malignancy in the cervix is proven almost beyond doubt. The present study is aimed at the role of two types of HPV 16 and 18 in the initiation of oral premalignant and squamous cell carcinoma. The study also aims at using polymerase chain reaction (PCR) in finding out the prevalence of these types diagnosed histologically as oral leukoplakia and oral squamous cell carcinoma and prevalence of its association with the habit of tobacco use. In the present study, 45 patients having histopathologically confirmed oral squamous cell carcinoma in the age range of 32-85 years were selected along with 20 histopathologically confirmed oral leukoplakia in the age range 22-66 years. All the samples were subjected to polymerase chain reaction. The PCR reaction was carried out in PTC 200 thermo-cycler [MJ Research Inc, Watertown, MA, USA]. The site prevalence and co-infection rate of these two types of viruses are being analyzed using very simple non-invasive scrapings obtained from fresh scrapings and found to be really high. It was also observed that 73.3% (33/45) of the oral squamous cell carcinoma patients were positive for oral HPV type 16 while 71.1% (32/45) were positive for HPV type 18 infection and 57.7% (26/45) were found to have both HPV type 16 and HPV type 18 infections. HPV type 16, 18, and co-infection of both types showed high prevalence in oral squamous cell carcinoma.The prevalence of HPV type 18 was found to be higher than HPV type 16 and co-infection in oral leukoplakia. It was observed that the tongue and palate lesions in the oral squamous cell

Selective Killing Effects of Cold Atmospheric Pressure Plasma with NO Induced Dysfunction of Epidermal Growth Factor Receptor in Oral Squamous Cell Carcinoma.

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Jung-Hwan Lee

Full Text Available The aim of this study is to investigate the effects of cold atmospheric pressure plasma (CAP-induced radicals on the epidermal growth factor receptor (EGFR, which is overexpressed by oral squamous cell carcinoma, to determine the underlying mechanism of selective killing. CAP-induced highly reactive radicals were observed in both plasma plume and cell culture media. The selective killing effect was observed in oral squamous cell carcinoma compared with normal human gingival fibroblast. Degradation and dysfunction of EGFRs were observed only in the EGFR-overexpressing oral squamous cell carcinoma and not in the normal cell. Nitric oxide scavenger pretreatment in cell culture media before CAP treatment rescued above degradation and dysfunction of the EGFR as well as the killing effect in oral squamous cell carcinoma. CAP may be a promising cancer treatment method by inducing EGFR dysfunction in EGFR-overexpressing oral squamous cell carcinoma via nitric oxide radicals.

Selective Killing Effects of Cold Atmospheric Pressure Plasma with NO Induced Dysfunction of Epidermal Growth Factor Receptor in Oral Squamous Cell Carcinoma.

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Lee, Jung-Hwan; Om, Ji-Yeon; Kim, Yong-Hee; Kim, Kwang-Mahn; Choi, Eun-Ha; Kim, Kyoung-Nam

2016-01-01

The aim of this study is to investigate the effects of cold atmospheric pressure plasma (CAP)-induced radicals on the epidermal growth factor receptor (EGFR), which is overexpressed by oral squamous cell carcinoma, to determine the underlying mechanism of selective killing. CAP-induced highly reactive radicals were observed in both plasma plume and cell culture media. The selective killing effect was observed in oral squamous cell carcinoma compared with normal human gingival fibroblast. Degradation and dysfunction of EGFRs were observed only in the EGFR-overexpressing oral squamous cell carcinoma and not in the normal cell. Nitric oxide scavenger pretreatment in cell culture media before CAP treatment rescued above degradation and dysfunction of the EGFR as well as the killing effect in oral squamous cell carcinoma. CAP may be a promising cancer treatment method by inducing EGFR dysfunction in EGFR-overexpressing oral squamous cell carcinoma via nitric oxide radicals.

The role of mast cells in oral squamous cell carcinoma

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Gudiseva, Swetha; Chitturi, Raviteja; Anumula, Vamsikrishna; Poosarla, Chandrashekar; Baddam, Venkat Ramana Reddy

2017-01-01

The mast cells are initial effective lineage in both humoral and adaptive immunity. They are ubiquitous in skin, mucosa, and in function. They contain biologically essential and dynamic mediators in healthy and harmful conditions of tissue. Mast cell malfunctioning could be attributed to various chronic allergic diseases. Considerately, emerging evidence of mast cell involvement in various cancers shows them to have both positive and negative roles in tumour growth. It mostly indulges in tumour progression and metastasis via angiogenesis, extracellular matrix degradation, and mitogenic activity in the tumour microenvironment. The current paper reviewed research papers on mast cells in oral squamous cell carcinoma through the PubMed database from 1980 to the present date. The present paper is an attempt to summarise the research reports on the role of mast cells in oral squamous cell carcinoma. Further to this note, this paper also outlines the role of mast cells in normal physiological processes and tumour biology. PMID:28435394

The role of mast cells in oral squamous cell carcinoma

Directory of Open Access Journals (Sweden)

Swetha Gudiseva

2017-03-01

Full Text Available The mast cells are initial effective lineage in both humoral and adaptive immunity. They are ubiquitous in skin, mucosa, and in function. They contain biologically essential and dynamic mediators in healthy and harmful conditions of tissue. Mast cell malfunctioning could be attributed to various chronic allergic diseases. Considerately, emerging evidence of mast cell involvement in various cancers shows them to have both positive and negative roles in tumour growth. It mostly indulges in tumour progression and metastasis via angiogenesis, extracellular matrix degradation, and mitogenic activity in the tumour microenvironment. The current paper reviewed research papers on mast cells in oral squamous cell carcinoma through the PubMed database from 1980 to the present date. The present paper is an attempt to summarise the research reports on the role of mast cells in oral squamous cell carcinoma. Further to this note, this paper also outlines the role of mast cells in normal physiological processes and tumour biology.

Effect of vitamin E on protein bound carbohydrate complexes in radiation treated oral squamous cell carcinoma patients

International Nuclear Information System (INIS)

Chitra, S.; Shyamala Devi, C.S.

2008-01-01

Serum glycoproteins were evaluated in oral squamous cell carcinoma patients treated with radiotherapy and also the effect of vitamin E was studied. Cell surface glycoconjugates are important parameters in the detection of malignancy. Thus, the objective of the present study is to evaluate the efficacy of vitamin E on glycoproteins in oral cavity cancer patients treated with radiotherapy. The study includes 26 age and sex matched normal healthy individuals and 26 patients with squamous cell carcinoma of oral cavity. These patients were divided into two groups, one for radiotherapy alone (at a dosage of 6000 cGy in five fractions per week for a period of six weeks) and the other for radiotherapy plus vitamin E supplementation (at a dosage of 400 IU/day of vitamin E) for the entire period of radiotherapy. Levels of hexose, hexosamine, fucose and sialic acid were increased in oral squamous cell carcinoma patients and a significant decrease was observed in radiation treated patients when compared to control. The levels of glycoconjugates were significantly decreased in radiation treated patients supplemented with vitamin E. This measurement may be useful in assessing disease progression and identifying patients resistant to therapy and a possible role of vitamin E on reduction in glycoconjugate levels of radiation treated oral squamous cell carcinoma patients. (author)

JNK-associated scattered growth of YD-10B oral squamous carcinoma cells while maintaining the epithelial phenotype

International Nuclear Information System (INIS)

Lee, Gayoung; Kim, Hyun-Man

2017-01-01

Cell scattering of epithelial carcinoma cancer cells is one of the critical event in tumorigenesis. Cells losing epithelial cohesion detach from aggregated epithelial cell masses and may migrate to fatal organs through metastasis. The present study investigated the molecular mechanism by which squamous cell carcinoma cells grow scattered at the early phase of transformation while maintaining the epithelial phenotype. We studied YD-10B cells, which are established from human oral squamous cell carcinoma, because the cells grow scattered without the development of E-cadherin junctions (ECJs) under routine culture conditions despite the high expression of functional E-cadherin. The functionality of their E-cadherin was demonstrated in that YD-10B cells developed ECJs, transiently or persistently, when they were cultured on substrates coated with a low amount of fibronectin or to confluence. The phosphorylation of JNK was up-regulated in YD-10B cells compared with that in human normal oral keratinocyte cells or human squamous cell carcinoma cells, which grew aggregated along with well-organized ECJs. The suppression of JNK activity induced the aggregated growth of YD-10B cells concomitant with the development of ECJs. These results indicate for the first time that inherently up-regulated JNK activity induces the scattered growth of the oral squamous cell carcinoma cells through down-regulating the development of ECJ despite the expression of functional E-cadherin, a hallmark of the epithelial phenotype. - Highlights: • JNK dissociates YD-10B oral squamous cell carcinoma cells. • JNK suppresses the development of E-cadherin junctions of oral carcinoma cells. • Suppression of JNK activity reverses the scattered growth of oral carcinoma cells.

Clinical and Histologic Features Compared with AgNOR Count in Oral Leukoplakia, Erosive Lichen Planus, Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma

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Sarbjeet Singh

2006-01-01

The aim of the study was to correlate and compare AgNOR count in speckled leukoplakia, oral lichen planus, oral submucous fibrosis and in oral squamous cell carcinoma and to assess if AgNOR count could contribute to the pre-therapeutic assessment of the biologic aggressiveness of the disease and to detect malignant potential of premalignant lesion and conditions which could render us to assess the prognosis of the disease.

Assessment of Tissue Eosinophilia as a Prognosticator in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma—An Image Analysis Study

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Megha Jain

2014-01-01

Full Text Available Association of tissue eosinophilia with oral squamous cell carcinoma has shown variable results ranging from favourable to unfavourable or even having no influence on prognosis. Also, very few studies have been done to know the role of eosinophils in premalignancy. So the present study investigated role of eosinophilic infiltration in oral precancer and cancer and its possible use as a prognosticator. 60 histopathologically proven cases (20 cases each of metastatic and nonmetastatic oral squamous cell carcinoma and oral leukoplakia with dysplasia of various grades were included. Congo red is used as a special stain for eosinophils. Each specimen slide was viewed under high power in 10 consecutive microscopic fields for counting of eosinophils. As a result, a significant increase in eosinophil count was found in oral carcinomas compared to dysplasia. Nonmetastatic cases showed higher counts than metastatic carcinomas. So, it is concluded that eosinophilia is a favourable histopathological prognostic factor in oral cancer. Moreover, higher eosinophil counts in carcinoma group compared to dysplasia group proved that they might have a role in stromal invasion thus suggesting that quantitative assessment of tissue eosinophilia should become a part of the routine histopathological diagnosis for oral precancer and OSCC.

Expression of Podoplanin in Different Grades of Oral Squamous Cell ...

African Journals Online (AJOL)

Background: The expression of podoplanin is up‑regulated in a number of different human cancers, including squamous cell carcinoma of the oral cavity and its relationship with tumor invasion raises the possibility that podoplanin expression could be used as a biomarker for diagnosis and prognosis. Aim: The aim of the ...

HPV prevalence in a Mid-European oral squamous cell cancer population: a cohort study.

Science.gov (United States)

Dalla Torre, Daniel; Burtscher, Doris; Soelder, Elisabeth; Offermanns, Vincent; Rasse, Michael; Puelacher, Wolfgang

2018-04-29

HPV infection has been investigated intensively regarding oropharyngeal carcinoma. However, there is still lack of knowledge about the impact of oral HPV infections concerning oral squamous cell carcinoma. The present study investigates the prevalence of oral HPV infection in such patients, identifying possible differences between HPV+ and HPV- patients. 106 consequent patients were investigated. After completion of a study questionnaire regarding risk factors, a brush smear sample was taken in each subject to identify the individual oral HPV status (overall/low risk/high risk). 35.8% of the patients were tested positive for HPV in the oral cavity (14% low risk, 28.3% high risk). Patients with oral HPV infection and high risk HPV infection were significantly younger (pHPV infection. Finally, patients with high risk oral HPV infection had experienced more tooth extractions during their lifetime. Oral HPV infections may influence the course of disease of oral squamous cell carcinoma as HPV+ patients are about 10 years younger. It seems that high alcohol consumption facilitates high risk HPV infection. It may be presumed that both alcohol consumption and high risk oral HPV infection act synergistically, explaining earlier cancer onset. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Expression of Epstein-Barr virus among oral potentially malignant disorders and oral squamous cell carcinomas in the South Indian tobacco-chewing population.

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Reddy, Sujatha S; Sharma, Shivani; Mysorekar, Vijaya

2017-07-01

Oral cancer is the sixth most common malignancy in the world. Viruses are the causative agents of approximately 10-15% of all cancers worldwide (Cancers, 6, 2014 and 2155). The tumorigenic roles of Epstein-Barr virus in oral cancer are unclear. Literature search results are conflicting and dependent on various factors such as geographical/regional variations, sociocultural lifestyles, dietary habits, chewing/smoking tobacco habit. This study is the first original observation about frequency of Epstein-Barr virus among South Indian tobacco-chewing patients to elucidate its involvement in oral carcinogenesis and to know whether this can be a valuable diagnostic and prognostic indicator. A total number of 75 tobacco chewer subjects aged between 23 and 76 years with histopathologically confirmed oral potentially malignant disorders (25), oral squamous cell carcinoma (25), and age-matched healthy controls (25) formed the study group. Immunohistochemical expression of Epstein-Barr virus latent membrane protein 1 was assessed among cases and healthy controls. Out of the total 75 subjects, six subjects (8%) were positive for Epstein-Barr virus antigen and 69 subjects (92%) negative. The antigen positivity was observed among two cases of moderately differentiated oral squamous cell carcinoma, two cases of leukoplakia, and two healthy controls. No significant association between Epstein-Barr virus positivity was observed among oral potentially malignant disorders and oral squamous cell carcinoma among South Indian tobacco-chewing patients. This can be partially explained by the methodology employed, by the patient population analyzed and different habits in various geographical regions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Subclonal Structure and Genomic Evolution of Oral Squamous Cell Carcinoma Revealed by Ultra-deep Sequencing

DEFF Research Database (Denmark)

Tabatabaeifar, Siavosh; Thomassen, Mads; Larsen, Martin Jakob

Background: Oral squamous cell carcinoma (OSCC), a subgroup of head and neck squamous cell carcinoma (HNSCC), is primarily caused by alcohol consumption and tobacco use. Recent DNA sequencing studies suggests that HNSCC are very heterogeneous between patients; however the intra-patient subclonal...

Serum Endostatin Levels in Oral Squamous Cell Carcinoma

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Maryam Mardani

2018-05-01

Full Text Available Introduction: Endostatin is a C-­terminal proteolytic fragment of collagen XVIII and, as with angiostatin and thrombospondin, is known as an anti­angiogenic agent. The aim of this study was to assess the level of serum endostatin in patients with oral squamous cell carcinoma (SCC, and its association with the clinicopathological characteristics of the tumor.   Materials and Methods:  Using an enzyme-linked immunosorbent assay (ELISA kit, we investigated the circulating levels of endostatin in the blood serum of 45 patients with oral SCC and 45 healthy controls.   Results: The mean level of serum endostatin in patients was significantly lower (68.8±85 ng/ml than in healthy controls (175.6±73 ng/ml (P

The Danish national guidelines for treatment of oral squamous cell carcinoma

DEFF Research Database (Denmark)

Bilde, Anders; von Buchwald, Christian; Johansen, Jørgen

2006-01-01

The treatment strategy for oral squamous cell carcinoma in Denmark has traditionally varied between the different head and neck oncology centres. A study group within the Danish Society for Head and Neck Oncology (DSHHO) was formed with the aim of optimising and standardising the treatment strategy...

Estudo de p27, p21, p16 em epitélio escamoso normal, papiloma escamoso e carcinoma de células escamosas da cavidade oral Comparative analysis of the immunohistochemistry expression of p27, p21WAF/Cip1, and p16INK4a in oral normal epithelium, squamous papilloma and squamous cell carcinoma

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Ana Beatriz Piazza Queiroz

2009-12-01

Full Text Available INTRODUÇÃO E OBJETIVO: O tipo de câncer oral mais frequente é o carcinoma de células escamosas, que corresponde a 95% dos casos(9. O papiloma escamoso oral é uma neoplasia benigna normalmente associada à infecção pelo papilomavírus humano (HPV(21. A análise da literatura mostra alterações nos genes reguladores do ciclo celular p27, p21WAF/Cip1 e p16INK4a, porém sem uma definição de seus papéis na carcinogênese oral. O objetivo foi caracterizar imuno-histoquimicamente p27, p21WAF/Cip1 e p16NK4a em epitélio escamoso normal, papilomas escamosos e carcinomas de células escamosas da cavidade oral. MÉTODOS: Imuno-histoquímica para p27, p21WAF/Cip1 e p16NK4a em 32 casos de epitélio escamoso normal, 30 casos de papiloma escamoso e 34 de carcinoma de células escamosas da cavidade oral. RESULTADOS: p27: 97,06% dos casos de carcinoma de células escamosas apresentaram imunopositividade focal. O grupo papiloma escamoso apresentou 33,33% e o grupo controle, 18,75%. p21WAF/Cip1: 100% de imunopositividade focal tanto no grupo controle como no grupo carcinoma de células escamosas, e 90% no grupo papiloma escamoso. p16INK4a: 100% de imunopositividade focal para os grupos controle e papiloma escamoso, e 94% para o grupo carcinoma de células escamosas. CONCLUSÃO: Imuno-histoquimicamente demonstrou-se diferença significativa para p27 quando feita comparação dos grupos controle e papiloma escamoso com o grupo carcinoma de células escamosas. O p21WAF/Cip1 não demonstrou poder de diferenciar os grupos analisados. O p16INK4a apresentou imunopositividade difusa em uma minoria dos casos do grupo carcinoma de células escamosas. O grupo papiloma escamoso se comportou de maneira similar ao grupo controle em relação aos três marcadores.INTRODUCTION: The most frequent type of oral cancer is the squamous cell carcinoma, which corresponds to 95% of the cases(9.The oral squamous papilloma is a benign neoplasia, commonly associated with

Overexpression of protease nexin-1 mRNA and protein in oral squamous cell carcinomas

DEFF Research Database (Denmark)

Gao, Shan; Krogdahl, Annelise; Sørensen, Jens Ahm

2007-01-01

-1 has been almost totally neglected. We have now compared the level of PN-1 mRNA in 20 cases of oral squamous cell carcinomas and in matched samples of the corresponding normal oral tissues. We found that the average PN-1 mRNA level in tumours and normal tissues was significantly different, being...... increased up to 13 fold in tumour samples compared with the average level in normal tissues. The PN-1 mRNA level was significantly higher in tumours from patients with lymph node metastasis than in tumours from patients without. We could conclude that PN-1 is frequently overexpressed in oral squamous cell...... carcinomas and that its level may correlate with the occurrence of lymph node metastasis. We hypothesise that PN-1 may have a tumour biological function similar to that of PAI-1....

Squamous cell carcinoma of the oral cavity

International Nuclear Information System (INIS)

Lindeloev, B.; Kirkegaard, J.; Hansen, H.S.; Copenhagen Univ. Hospital

1990-01-01

Three hundred and four patients with squamous cell carcinomas of the oral cavity were treated at the Finsen Institute in cooperation with the ENT-surgical departments between 1978 and 1982. The primary treatment consisted of radiotherapy alone in 74%, surgery alone in 4%, and a combination of radiotherapy and surgery in 15% of the patients. 2% received other treatment (cryotherapy), 5% did not complete the planned radiotherapy, and 1% were not treated at all. Of 203 patients with tumour remnant or first recurrence, 45% were operated, 2% received radiotherapy, and 2% combined treatment. This treatment strategy made 38% of the patients free of disease in the follow-up period (3 1/2 to 8 years) or until the patients died from other causes. Fifty-nine percent of the patients died from their oral carcinomas. Tumour size (T), lymph node status (N), and tumour stage were as expected important prognostic factors. (orig.)

Analysis of human papilloma virus in oral squamous cell carcinoma using p16: An immunohistochemical study

Science.gov (United States)

Patil, S.; Rao, R. S.; Amrutha, N.; Sanketh, D. S.

2014-01-01

Aims: The aim of this study is to evaluate the expression of human papilloma virus (HPV) in oral squamous cell carcinoma (OSCC) and to correlate the association of HPV in histological grades of OSCC using p16 (p16INK4a) immunohistochemistry (IHC). Subjects and Methods: This study consists of 30 histological diagnosed cases of OSCC (10-well-differentiated oral squamous cell carcinoma [WDOSCC], 10-moderately differentiated oral squamous cell carcinoma [MDOSCC] and 10-poorly differentiated oral squamous cell carcinoma [PDOSCC]). The sections were subjected to IHC procedure using p16. Two parameters in immunohistochemical p16 expression were evaluated by 3 observers based on the criteria by Galgano M. Tetal (2010) (a) percentage of p16 positive cases (b) pattern of p16 staining in various grades of OSCC. Statistical Analysis Used: Kappa test. Results: Totally, 30 samples of 0SCC, p16 positivity was noted in 26/30 (86.66%). Of 26 positive cases, p16 staining was positive in 7/10 (70%) of WDOSCC, 9/10 (90%) in MDOSCC and, 10/10 (100%) PDOSCC. Incidentally, we also found single dispersed cell staining in WDOSCC, patchy staining in MDOSCC and more diffuse staining pattern predominant in PDOSCC. Conclusions: Our study revealed an association between HPV and OSCC. Diffuse staining pattern was noted in PDOSCC, which in turn depicts the increase viral overload, which might have an influence on its aggressive behavior. PMID:24818098

Squamous cell carcinoma from oral lichen planus: a case report of a lesion with 28 years of evolution.

Science.gov (United States)

Silveira, Wanessa da Silva; Bottezini, Ezequiel Gregolin; Linden, Maria Salete; Rinaldi, Isadora; Paranhos, Luiz Renato; de Carli, João Paulo; Trentin, Micheline; Dos Santos, Pâmela Letícia

2017-12-01

Lichen planus (LP) is a relatively common mucocutaneous disease with autoimmune etiology. Considering its malignancy potential, it is important to define the correct diagnosis, treatment, and clinical follow-up for patients with LP so that the disease is not diagnosed late, thus hindering the chances of curing the disease. This study aims to describe a clinical case of oral squamous cell carcinoma, potentially originated from LP. The patient is undergoing clinical and histopathological follow-up. A 64-year-old Caucasian male patient presented with a proliferative verrucous lesion on the tongue and sought treatment at the School of Dentistry, University of Passo Fundo (UPF), Passo Fundo, Brazil. He claimed the lesion had been present since 1988, and had been initially diagnoses as "oral lichen planus." The physical exam presented three diagnostic hypotheses: plaque-like oral LP, verrucous carcinoma, and squamous cell carcinoma. After incisional biopsy and histopathological analysis, squamous cell carcinoma was diagnosed, probably originating from oral LP. The case study shows that malignancy from oral LP is possible, which justifies periodic clinical and histopathological follow-up, as well as the elimination of risk factors for carcinoma in patients with oral LP.

Oral squamous cell carcinoma following treatment of acute lymphoblastic leukaemia

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Waal, R.I.F. van der; Waal, I. van der [Univ. Hospital Vrije Univ., Dept. of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam (Netherlands); Veerman, A.J.P. [Univ. Hospital Vrije Univ., Dept. of Paediatric Oncology, Amsterdam (Netherlands); Snow, G.B. [Univ. Hospital Vrije Univ., Dept. of Otorhinolaryngology, Amsterdam (Netherlands)

1997-02-01

With substantially increased survival after most paediatric cancers over the past decades have come the late sequelae of treatment. Of all late complications of treatment, second malignancies are generally considered to be the most serious. We report on a 20-year-old man with an oral squamous cell carcinoma 17 years after initial chemotherapy and irradiation for acute lymphoblastic leukaemia. Although occurrence of the oral malignancy in this patient could have been treatment-related, one should keep in mind that the occurrence of second tumours may also be based on a shared genetic aetiology. (au) 9 refs.

Oral squamous cell carcinoma following treatment of acute lymphoblastic leukaemia

International Nuclear Information System (INIS)

Waal, R.I.F. van der; Waal, I. van der; Veerman, A.J.P.; Snow, G.B.

1997-01-01

With substantially increased survival after most paediatric cancers over the past decades have come the late sequelae of treatment. Of all late complications of treatment, second malignancies are generally considered to be the most serious. We report on a 20-year-old man with an oral squamous cell carcinoma 17 years after initial chemotherapy and irradiation for acute lymphoblastic leukaemia. Although occurrence of the oral malignancy in this patient could have been treatment-related, one should keep in mind that the occurrence of second tumours may also be based on a shared genetic aetiology. (au) 9 refs

A clinical study of thallium-201 SPECT in the diagnostic imaging of oral squamous cell carcinomas

International Nuclear Information System (INIS)

Satoh, Hitoshi

2003-01-01

Recently the usefulness of thallium 201 chloride (201Tl) as a tumor imaging agent for various tumors has been reported. However, the application of 201Tl SPECT to oral squamous cell carcinomas has not been established. The purpose of this study is to investigate the usefulness of 201Tl SPECT in the assessment of malignancy or in the differential diagnosis of oral squamous cell carcinomas from inflammatory diseases. Thirty-two patients with 33 primary oral squamous cell carcinomas and 4 patients with inflammatory disease were studied. SPECT images were acquired 15 minutes (early image) and 3 hours (delayed image) after the intravenous injection with 74 MBq 201Tl, and then early uptake ratio (ER), delayed uptake ratio (DR), and retention index (RI) were measured. The relations between these parameters and the size, the site, the degree of differentiation and the mode of invasion of the primary tumor were analyzed statistically. 201Tl SPECT correctly identified 32 of the 33 tumors, with 32 patients having oral squamous cell carcinoma, making the positive rate 97%. Significant negative correlation was observed between RI and major or minor axis of tumors; therefore, this study revealed that RI was influenced by the size of a tumor. In comparison with the average value of RI according to histopathological diagnosis, there was statistically significant difference (p=0.011) between carcinomas (0.80±0.16, n=30) and inflammatory diseases (0.58±0.04, n=4); thus, it was supposed that differential diagnosis between them could be possible. About the tumors with the range of minor-axis 20 mm-40 mm for little influence of tumor size to the RI, the tendency to decrease for the RI of well-differentiated group or low-invasive group was seen. For oral squamous cell carcinomas, 201Tl SPECT had a high positive rate. The application was suggested for use in the differential diagnosis between inflammatory disease and carcinomas, where clinical usefulness could be expected. (author)

Acetaldehyde production and microbial colonization in oral squamous cell carcinoma and oral lichenoid disease.

Science.gov (United States)

Marttila, Emilia; Uittamo, Johanna; Rusanen, Peter; Lindqvist, Christian; Salaspuro, Mikko; Rautemaa, Riina

2013-07-01

The main aim of this prospective study was to explore the ability of the oral microbiome to produce acetaldehyde in ethanol incubation. A total of 90 patients [30 oral squamous cell carcinoma (OSCC); 30 oral lichenoid disease (OLD); 30 healthy controls (CO)] were enrolled in the study. Microbial samples were taken from the mucosa using a filter paper method. The density of microbial colonization was calculated and the spectrum analyzed. Microbial acetaldehyde production was measured by gas chromatography. The majority (68%) of cultures produced carcinogenic levels of acetaldehyde (>100 μM) when incubated with ethanol (22 mM). The mean acetaldehyde production by microbes cultured from smoker samples was significantly higher (213 μM) than from non-smoker samples (141 μM) (P=.0326). The oral microbiota from OSCC, OLD patients and healthy individuals are able to produce carcinogenic levels of acetaldehyde. The present provisional study suggests smoking may increase the production of acetaldehyde. Copyright © 2013 Elsevier Inc. All rights reserved.

FBXW7 expression affects the response to chemoradiotherapy and overall survival among patients with oral squamous cell carcinoma: A single-center retrospective study.

Science.gov (United States)

Arita, Hidetaka; Nagata, Masashi; Yoshida, Ryoji; Matsuoka, Yuichiro; Hirosue, Akiyuki; Kawahara, Kenta; Sakata, Junki; Nakashima, Hikaru; Kojima, Taku; Toya, Ryo; Murakami, Ryuji; Hiraki, Akimitsu; Shinohara, Masanori; Nakayama, Hideki

2017-10-01

FBXW7 (F-box and WD repeat domain containing-7) is a tumor suppressor protein that regulates the degradation of various oncoproteins in several malignancies. However, limited information is available regarding FBXW7 expression in oral squamous cell carcinoma. Therefore, this study aimed to determine the clinical significance of FBXW7 expression in oral squamous cell carcinoma. The FBXW7 expression patterns in oral squamous cell carcinoma and adjacent normal tissues from 15 patients who underwent radical resection were evaluated using quantitative real-time polymerase chain reaction and immunohistochemical staining. In addition, immunohistochemistry was performed using paraffin-embedded sections from biopsy specimens obtained from 110 patients with oral squamous cell carcinoma who underwent surgery after 5 fluorouracil-based chemoradiotherapy. The associations of FBXW7 expression with various clinicopathological features and prognosis were evaluated in these patients. As a results, in the 15 matched samples, the FBXW7 expression was significantly decreased in the oral squamous cell carcinoma tissues compared to that in the adjacent normal tissues. In the clinicopathological analysis, compared to high protein expression, low FBXW7 expression was found to significantly associate with a poor histological response to preoperative chemoradiotherapy. Kaplan-Meier curve analysis revealed that low FBXW7 expression was significantly associated with a poor prognosis, and FBXW7 expression was found to be an independent predictor of overall survival in the multivariate analysis. Our results suggest that FBXW7 may function as a tumor suppressor protein in oral squamous cell carcinoma. In addition, FBXW7 could be a potential biomarker for predicting not only the clinical response to chemoradiotherapy but also overall survival in patients with oral squamous cell carcinoma.

Impact of Somatic Mutations in the D-Loop of Mitochondrial DNA on the Survival of Oral Squamous Cell Carcinoma Patients

Science.gov (United States)

Lin, Jin-Ching; Wang, Chen-Chi; Jiang, Rong-San; Wang, Wen-Yi; Liu, Shih-An

2015-01-01

Objectives The aim of this study was to investigate somatic mutations in the D-loop of mitochondrial DNA (mtDNA) and their impact on survival in oral squamous cell carcinoma patients. Materials and Methods Surgical specimen confirmed by pathological examination and corresponding non-cancerous tissues were collected from 120 oral squamous cell carcinoma patients. The sequence in the D-loop of mtDNA from non-cancerous tissues was compared with that from paired cancer samples and any sequence differences were recognized as somatic mutations. Results Somatic mutations in the D-loop of mtDNA were identified in 75 (62.5%) oral squamous cell carcinoma patients and most of them occurred in the poly-C tract. Although there were no significant differences in demographic and tumor-related features between participants with and without somatic mutation, the mutation group had a better survival rate (5 year disease-specific survival rate: 64.0% vs. 43.0%, P = 0.0266). Conclusion Somatic mutation in D-loop of mtDNA was associated with a better survival in oral squamous cell carcinoma patients. PMID:25906372

Oral Cavity Squamous Cell Carcinoma - Characteristics and Survival in Aboriginal and Non-Aboriginal Western Australians

OpenAIRE

Frydrych, A.M; Slack-Smith, L.M; Parsons, R; Threlfall, T

2014-01-01

Background: Squamous cell carcinoma (SCC) is the most common type of malignancy affecting the oral cavity. While exposures to main risk factors for oral SCC such as smoking and alcohol use are higher amongst the Aboriginal people, little is known about oral cancer in this population. This study aimed to describe characteristics and survival of oral SCC in Aboriginal and non-Aboriginal Western Australians. Methods: All primary oral SCC cases reported to the Western Australian Cancer Registry (...

Sentinel lymph node biopsy in node-negative squamous cell carcinoma of the oral cavity and oropharynx.

LENUS (Irish Health Repository)

Burns, P

2012-02-01

OBJECTIVES: Considerable controversy exists regarding the merits of elective neck dissection in patients with early stage oral cavity and oropharyngeal squamous cell carcinoma. It is highly desirable to have a method of identifying those patients who would benefit from further treatment of the neck when they are clinically node-negative. The purpose of the present study was to examine the use of sentinel lymph node biopsy in identifying occult neck disease in a cohort of patients with node-negative oral cavity and oropharyngeal squamous cell carcinoma. DESIGN: We evaluated a total of 13 patients with oral cavity and oropharyngeal cancer who were clinically and radiologically node-negative. RESULTS: A sentinel lymph node was found in all 13 patients, revealing metastatic disease in five patients, four of whom had one or more positive sentinel lymph nodes. There was one false negative result, in which the sentinel lymph node was negative for tumour whereas histological examination of the neck dissection specimen showed occult disease. CONCLUSION: In view of these findings, we would recommend the use of sentinel lymph node biopsy in cases of oral cavity and oropharyngeal squamous cell carcinoma, in order to aid the differentiation of those patients whose necks are harbouring occult disease and who require further treatment.

[Study of testicular cancer gene expression in samples of oral leukoplakia and squamous cell carcinoma of the mouth].

Science.gov (United States)

Skorodumova, L O; Muraev, A A; Zakharova, E S; Shepelev, M V; Korobko, I V; Zaderenko, I A; Ivanov, S Iu; Gnuchev, N V; Georgiev, G P; Larin, S S

2012-01-01

Cancer-testis (CT) antigens are normally expressed mostly in human germ cells, there is also an aberrant expression in some tumor cells. This expression profile makes them potential tumor growth biomarkers and a promising target for tumor immunotherapy. Specificity of CT genes expression in oral malignant and potentially malignant diseases, e.g. oral leukoplakia, is not yet studied. Data on CT genes expression profile in leukoplakia would allow developing new diagnostic methods with potential value for immunotherapy and prophylaxis of leukoplakia malignization. In our study we compared CT genes expression in normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma. We are the first to describe CT genes expression in oral leukoplakia without dysplasia. This findings make impossible differential diagnosis of oral leukoplakia and squamous cell carcinoma on the basis of CT genes expression. The prognostic value of CT genes expression is still unclear, therefore the longitudinal studies are necessary.

Cyclin D1 Expression and Its Correlation with Histopathological Differentiation in Oral Squamous Cell Carcinoma

Directory of Open Access Journals (Sweden)

Swati Saawarn

2012-01-01

Full Text Available Background. Cyclin D1 regulates the G1 to S transition of cell cycle. Its deregulation or overexpression may lead to disturbance in the normal cell cycle control and tumour formation. Overexpression of cyclin D1 has been reported in various tumors of diverse histogenesis. This case control retrospective study was carried out to study the immunohistochemical reactivity and expression of cyclin D1 and its association with site, clinical staging, and histopathological differentiation of oral squamous cell carcinoma (OSCC. Methods. Forty formalin-fixed paraffin-embedded tissue blocks of biopsy specimens of oral squamous cell carcinoma were immunohistochemically evaluated for expression of cyclin D1. Results. Cyclin D1 expression was seen in 45% cases of OSCC. It did not correlate with site and clinical staging. Highest expression was seen in well-differentiated, followed by moderately differentiated, and poorly differentiated squamous cell carcinomas, with a statistically significant correlation. Conclusion. Cyclin D1 expression significantly increases with increase in differentiation.

Oral squamous cell carcinoma: survival, recurrence and death

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Antônio Camilo Souza Cruz

2014-10-01

Full Text Available This paper was based in data survey from macro and microscopic oral lesions characteristics, personal data and medical history of patients diagnosed with oral squamous cell carcinoma in the Lab of Pathological Anatomy from the Federal University of Alfenas from January 2000 to December 2010, establishing comparative parameters among clinical data, type of treatment, recurrence, survival and anatomic pathological characteristics of the lesions. Were analyzed the histopathological reports, dental and hospital records. The highest incidence was in white men, age between 50 and 60 years, married, with low education and socioeconomic levels. The beginning of treatment occurred in average 67 days after the histopathological diagnosis. The estimated survival of patients at five years was 42%. The consumption of alcohol and tobacco and the occurrence of metastasis were statistically significant for the increase of recurrence and lethality.

Human papilloma virus in oral squamous cell carcinoma in a Mexican population.

Science.gov (United States)

Ibieta, Blanca R; Lizano, Marcela; Fras-Mendivil, Mauricio; Barrera, José L; Carrillo, Adela; Ma Ruz-Godoy, Luz; Mohar, Alejandro

2005-03-01

To determine the human papilloma virus (HPV) infection in oral cancer and its association with smoking and drinking habits. A cross-sectional study was performed; samples were collected from 51 patients with histological diagnosis of squamous-cell carcinoma were collected at the Instituto Nacional de Cancerología in Mexico City. HPV infection was detected by polymerase chain reaction, and the clinical characteristics of this population were analyzed. Fifty samples out of 51 were positive for beta-globin; 21 (42%) cases were HPV-positive, and 14/21 were positive for HPV-16. We found more samples positive in men than in women (71% vs 29%). No differences were observed between HPV-positive and -negative patients in relation to smoking and drinking habits (81% vs 79%). HPV infection was present in 42% of patients with oral squamous-cell carcinoma (OSCC); HPV-16 was the most frequent type, identified in 66.6%. Other cofactors participate in the development of OSCC, independent of HPV infection.

Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

Science.gov (United States)

Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

2016-04-01

Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma variants: An update with special reference to HPV-related carcinomas

Science.gov (United States)

2014-01-01

Accurate identification of the microscopic risk factors of oral and oropharyngeal (OP) squamous cell carcinomas (SCC) and their morphologic variants is of at most importance, as these generally determine treatment modalities, prognosis and overall patient outcome. The great majority of oral and oropharyngeal squamous cell carcinomas are microscopically described as kerartinizing squamous cell carcinoma (KSCC). They bear certain resemblance to keratinizing stratified squamous epithelium. Tobacco habits and excessive consumption of alcoholic beverages have been considered to be the main etiologic agents in these carcinomas. The tumors occurred in older patients more commonly affected the oral tongue and floor of the mouth with well established morphologic risk factors including tumor grade, pattern of invasion and perineural involvement. Within the last 30 years however, the advent and expanding prevalence of high risk human papillomavirus (HPV) as an important etiologic agent for head and neck squamous cell carcinoma, particularly in the OP, has resulted in a significant change in the established morphologic criteria for risk assessment. The majority of HPV relate carcinomas of the OP are nonkeratinizing squamous cell carcinoma (NKSCC). These tumors are found to be more responsive to treatment with a favorable patient outcome and good prognosis. Consequently, alterations in treatment protocols aimed at de-escalation are currently being evaluated. More recently, other morphologic variants that are HPV positive are reported with increasing frequency in the OP and other head and neck sites. As a result, several clinical and pathologic questions have emerged. Importantly, whether the virus is biologically active in these tumors and involved in their pathogenesis, and second, what are the clinical implications with regard to patient management and outcome in the HPV-related variants. Examples of HPV-related squamous cell carcinoma variants that will be addressed here are

Biomarker MicroRNAs for Diagnosis of Oral Squamous Cell Carcinoma Identified Based on Gene Expression Data and MicroRNA-mRNA Network Analysis

Science.gov (United States)

Zhang, Hui; Li, Tangxin; Zheng, Linqing

2017-01-01

Oral squamous cell carcinoma is one of the most malignant tumors with high mortality rate worldwide. Biomarker discovery is critical for early diagnosis and precision treatment of this disease. MicroRNAs are small noncoding RNA molecules which often regulate essential biological processes and are good candidates for biomarkers. By integrative analysis of both the cancer-associated gene expression data and microRNA-mRNA network, miR-148b-3p, miR-629-3p, miR-27a-3p, and miR-142-3p were screened as novel diagnostic biomarkers for oral squamous cell carcinoma based on their unique regulatory abilities in the network structure of the conditional microRNA-mRNA network and their important functions. These findings were confirmed by literature verification and functional enrichment analysis. Future experimental validation is expected for the further investigation of their molecular mechanisms. PMID:29098014

Laser Raman detection for oral cancer based on a Gaussian process classification method

Science.gov (United States)

Du, Zhanwei; Yang, Yongjian; Bai, Yuan; Wang, Lijun; Zhang, Chijun; Chen, He; Luo, Yusheng; Su, Le; Chen, Yong; Li, Xianchang; Zhou, Xiaodong; Jia, Jun; Shen, Aiguo; Hu, Jiming

2013-06-01

Oral squamous cell carcinoma is the most common neoplasm of the oral cavity. The incidence rate accounts for 80% of total oral cancer and shows an upward trend in recent years. It has a high degree of malignancy and is difficult to detect in terms of differential diagnosis, as a consequence of which the timing of treatment is always delayed. In this work, Raman spectroscopy was adopted to differentially diagnose oral squamous cell carcinoma and oral gland carcinoma. In total, 852 entries of raw spectral data which consisted of 631 items from 36 oral squamous cell carcinoma patients, 87 items from four oral gland carcinoma patients and 134 items from five normal people were collected by utilizing an optical method on oral tissues. The probability distribution of the datasets corresponding to the spectral peaks of the oral squamous cell carcinoma tissue was analyzed and the experimental result showed that the data obeyed a normal distribution. Moreover, the distribution characteristic of the noise was also in compliance with a Gaussian distribution. A Gaussian process (GP) classification method was utilized to distinguish the normal people and the oral gland carcinoma patients from the oral squamous cell carcinoma patients. The experimental results showed that all the normal people could be recognized. 83.33% of the oral squamous cell carcinoma patients could be correctly diagnosed and the remaining ones would be diagnosed as having oral gland carcinoma. For the classification process of oral gland carcinoma and oral squamous cell carcinoma, the correct ratio was 66.67% and the erroneously diagnosed percentage was 33.33%. The total sensitivity was 80% and the specificity was 100% with the Matthews correlation coefficient (MCC) set to 0.447 213 595. Considering the numerical results above, the application prospects and clinical value of this technique are significantly impressive.

Laser Raman detection for oral cancer based on a Gaussian process classification method

International Nuclear Information System (INIS)

Du, Zhanwei; Yang, Yongjian; Bai, Yuan; Wang, Lijun; Zhang, Chijun; Chen, He; Luo, Yusheng; Su, Le; Chen, Yong; Li, Xianchang; Zhou, Xiaodong; Shen, Aiguo; Hu, Jiming; Jia, Jun

2013-01-01

Oral squamous cell carcinoma is the most common neoplasm of the oral cavity. The incidence rate accounts for 80% of total oral cancer and shows an upward trend in recent years. It has a high degree of malignancy and is difficult to detect in terms of differential diagnosis, as a consequence of which the timing of treatment is always delayed. In this work, Raman spectroscopy was adopted to differentially diagnose oral squamous cell carcinoma and oral gland carcinoma. In total, 852 entries of raw spectral data which consisted of 631 items from 36 oral squamous cell carcinoma patients, 87 items from four oral gland carcinoma patients and 134 items from five normal people were collected by utilizing an optical method on oral tissues. The probability distribution of the datasets corresponding to the spectral peaks of the oral squamous cell carcinoma tissue was analyzed and the experimental result showed that the data obeyed a normal distribution. Moreover, the distribution characteristic of the noise was also in compliance with a Gaussian distribution. A Gaussian process (GP) classification method was utilized to distinguish the normal people and the oral gland carcinoma patients from the oral squamous cell carcinoma patients. The experimental results showed that all the normal people could be recognized. 83.33% of the oral squamous cell carcinoma patients could be correctly diagnosed and the remaining ones would be diagnosed as having oral gland carcinoma. For the classification process of oral gland carcinoma and oral squamous cell carcinoma, the correct ratio was 66.67% and the erroneously diagnosed percentage was 33.33%. The total sensitivity was 80% and the specificity was 100% with the Matthews correlation coefficient (MCC) set to 0.447 213 595. Considering the numerical results above, the application prospects and clinical value of this technique are significantly impressive. (letter)

Investigation of trefoil factor expression in saliva and oral mucosal tissues of patients with oral squamous cell carcinoma

DEFF Research Database (Denmark)

Chaiyarit, Ponlatham; Utrawichian, Akasith; Leelayuwat, Chanvit

2012-01-01

Objectives The aims of our study were to determine levels of trefoil factor (TFF) peptides in saliva and oral mucosal tissues from patients with oral squamous cell carcinoma (OSCC), and to evaluate whether individual members of TFFs (TFF1, TFF2, and TFF3) might act as biomarkers of disease....... Materials and methods Saliva samples were from 23 healthy subjects and 23 OSCC patients. Tissue samples were collected from 32 normal oral mucosa (NOM) and 32 OSCC biopsy specimens. ELISA and immunohistochemical methods were used to evaluate the expression of TFF1, TFF2, and TFF3 in saliva and oral mucosal...... tissues, respectively. Results Expression of TFF2 and TFF3 in oral mucosal tissues of OSCC patients was strongly downregulated when compared to healthy subjects (p 

The value of lymphoscintigraphy for cervical sentinel lymph node detection in patients with clinically N0 oral squamous cell carcinoma

International Nuclear Information System (INIS)

Liu Sheng; Jiang Ningyi; Lu Xianping; Liang Jiugen

2005-01-01

Objective: To evaluate the value of lymphoscintigraphy for cervical sentinel lymph node (SLN) detection in patients with oral squamous cell carcinoma. Methods: Twenty-one patients with clinically N 0 oral squamous carcinoma underwent preoperative lymphoscintigraphy and intraoperative methylene blue location. The results were compared with pathological findings. Results: 1) The sensitivity of lymphoscintigraphy for detecting SLN was 100%(21/21), and methylene blue was 85% (17/20). 2)Both SLN biopsy and cervical ablative dissection confirmed that 33.3% (7/21) patients were with cervical lymph node metastasis. Fourteen non-metastatic SLNs comfirmed by biopsy were also proved with the findings of neck dissection, and the specificity was 100%. Conclusion: Lymphoscintigraphy can detect the cervical SLN and accurately predict cervical lymph node metastasis in patients with oral squamous cell carcinoma.(authors)

Novel diagnostic modalities for assessment of the clinically node-negative neck in oral squamous-cell carcinoma

NARCIS (Netherlands)

Leusink, F.K.; van Es, R.J.; Bree, R. de; Baatenburg de Jong, R.J.; van Hooff, S.R.; Holstege, F.C.; Slootweg, P.J.; Brakenhoff, R.H.; Takes, R.P.

2012-01-01

Oral squamous-cell carcinomas arise in mucosal linings of the oral cavity and frequently metastasise to regional lymph nodes in the neck. The presence of nodal metastases is a determinant of prognosis and clinical management. The neck is staged by palpation and imaging, but accuracy of these

Depression and anxiety in patients with oral squamous cell carcinoma

Institute of Scientific and Technical Information of China (English)

无

2006-01-01

PURPOSE: The aim of this study was to investigate symptoms of depression and anxiety in the patients with oral squamous cell carcinoma (OSCC). METHODS: 76 patients with oral squamous cell carcinoma participated in this program. All patients were rated with the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS). The mean scores of SAS and SDS were compared to those scores of the Norm of Chinese people. In addition, the different treatment results of the patients with different levels of anxiety and depression were studied. Further, the number of patients of SAS, SDS with more than 50 score were compared between primary cancer patients and recurrent cancer patients. RESULTS: The scores of SAS, SDS and the number of patients with more than 50 score in the patients group were obviously higher than those in Chinese Norm (P＜0.01).The levels of anxiety and depression in 32 patients with recurrent cancer were more severe than those of 44 patients with primary cancer. The patients with anxiety and/or depression showed poor prognosis. CONCLUSION: Anxiety and depression are common symptoms in patients with OSCC and have negative effects on the prognosis, thus the psychological intervention for the patients must be carried out.

Expression of SRSF3 is Correlated with Carcinogenesis and Progression of Oral Squamous Cell Carcinoma.

Science.gov (United States)

Peiqi, Liu; Zhaozhong, Guo; Yaotian, Yin; Jun, Jia; Jihua, Guo; Rong, Jia

2016-01-01

Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck with high mortality rates. The mechanisms of initiation and development of OSCC remain largely unknown. Dysregulated alternative splicing of pre-mRNA has been associated with OSCC. Splicing factor SRSF3 is a proto-oncogene and overexpressed in multiple cancers. The aim of this study was to uncover the relationship between SRSF3 and carcinogenesis and progression of oral squamous cell carcinoma. The expression of SRSF3 in oral normal, dysplasia, or carcinoma tissues was analyzed by immunohistochemistry. The expression levels of EMT-related genes were quantified by real-time quantitative RT-PCR. The expression of SRSF3 in DMBA treated primary cultured oral epithelial cells were analyzed by western blot. SRSF3 is overexpressed in oral cancer and moderate or severe dysplasia tissues. Patients with high grade cancer or lymphatic metastasis showed up-regulated expression of SRSF3. Knockdown of SRSF3 repressed the expression of Snail and N-cadherin in vitro. Carcinogen DMBA treated primary cultured oral epithelial cells showed significantly increased SRSF3 level than in control cells. Our results suggested that SRSF3 is associated with the initiation and development of OSCC and may be a biomarker and therapeutic target of OSCC.

Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line

OpenAIRE

Zhang Ping; Zhang Zhiyuan; Zhou Xiaojian; Qiu Weiliu; Chen Fangan; Chen Wantao

2006-01-01

Abstract Background Cisplatin is widely used for chemotherapy of head and neck squamous cell carcinoma. However, details of the molecular mechanism responsible for cisplatin resistance are still unclear. The aim of this study was to identify the expression of genes related to cisplatin resistance in oral squamous cell carcinoma cells. Methods A cisplatin-resistant cell line, Tca/cisplatin, was established from a cisplatin-sensitive cell line, Tca8113, which was derived from moderately-differe...

Salvage surgery for local failure of oral squamous cell carcinoma

International Nuclear Information System (INIS)

Omura, Ken; Harada, Hiroyuki; Shimamoto, Hiroaki

2003-01-01

Local failure rates following treatment for squamous cell carcinoma of the oral cavity have been reported to be in the range of 25%-48%. This study investigated the pattern of failure for squamous cell carcinoma (SCC) of the oral cavity and evaluated salvage surgery for local recurrent disease. The tumor files of 549 patients undergoing treatment for SCC of the oral cavity between 1980 and 2000 at Chiba Cancer Center Hospital were reviewed. Of 549 patients, 289 were initially treated with radiation therapy for their primary tumor, and 260 with surgery, either with or without radiation therapy. One hundred and sixty-one patients developed failures, yielding a failure rate of 29.3%. The site of recurrent tumor was local in 72 (13.1%) patients, regional in 89 (16.2%) patients, and distant in 5 (0.9%) patients. Local failure developed in 49 (17.0%) patients with radiation therapy and in 23 (8.8%) patients with surgery. Out of these 72 patients with local failure, 41 (56.9%) patients had salvage surgery for their disease. Twenty-five (73.5%) of the 34 patients initially treated with radiation therapy were salvaged with surgery, and 4 (57.1%) of the 7 patients initially treated with surgery were cured with further surgery. For the treatment of patients with local failure, the disease should be diagnosed more carefully than untreated disease. The disease that has recurred after radiation therapy may be more likely to be salvaged by surgery, however, the disease that has developed after surgery may have a limited indication for re-surgery. (author)

Oral Squamous Cell Carcinoma Mutational Profile in Taiwanese Population | Office of Cancer Clinical Proteomics Research

Science.gov (United States)

Oral squamous cell carcinoma (OSCC) is a major oral cancer subtype that is the fourth most common cancer affecting Taiwanese men. Despite known risk behaviors such as cigarette smoking, alcohol drinking, and betel nut chewing often indulged by Taiwanese men, the genetic contribution to the incidence or progression of OSCC has yet been elucidated in the Taiwanese population.

Two Unusual Cases of Oral Lichen Planus Arising After Oral Squamous Cell Carcinoma: Can Oral Cancer Trigger Autoimmunity?

Science.gov (United States)

Gissi, Davide Bartolomeo; Asioli, Sofia; Gabusi, Andrea

2017-08-01

Autoimmune diseases occur when the immune system fails to recognize self-antigens expressed on the body's own cells and attacks them. Oral lichen planus (OLP) is a chronic autoimmune mucocutaneous disease of the oral cavity characterized by white/red lesions. Considered a potentially malignant disorder, OLP evolution into oral squamous cell carcinoma (OSCC) is still a matter of debate. While chronic autoimmune inflammation is considered a potential risk factor for malignant transformation in many solid tumors, the opposite idea that cancer may trigger autoimmune responses remains controversial. We describe 2 patients who developed lesions clinically suggestive of OLP with histological evidence of lichenoid infiltration some time after OSCC removal, even in areas far from the neoplastic site. Neither patient had OLP before the diagnosis of OSCC, or reported exposure to OLP-associated etiologic factors, and neither. experienced tumor recurrence during follow-up. Our findings suggest that oral cancer remission may be linked to OLP development, but further studies are necessary to unveil the underlying mechanisms and possible prognostic implications.

Cytotoxic Components Against Human Oral Squamous Cell Carcinoma Isolated from Andrographis paniculata.

Science.gov (United States)

Suzuki, Ryuichiro; Matsushima, Yasuaki; Okudaira, Noriyuki; Sakagami, Hiroshi; Shirataki, Yoshiaki

2016-11-01

The 5-year survival rate of patients with oral cancer has remained approximately 50% during the past 30 years, possibly due to the poor tumor selectivity of conventional anticancer drugs. This prompted us to search for new candidates for anticancer drugs that have higher cytotoxicity and tumor selectivity. Dried leaves of Andrographis paniculata were supplied from a market in Shanghai. The methanolic fraction of A. paniculata was further fractionated to identify cytotoxic principles by spectroscopic analysis and comparison with literature values. Viable cell number was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method, and tumor specificity was calculated by relative cytotoxicity against oral squamous cell carcinoma cell lines compared to that against normal oral cells. Apoptosis induction was detected by cleaved poly (ADP-ribose) polymerase and caspase-3 on western blot analysis. Major cytotoxicity in the methanol extract of a leaf of A. paniculata was recovered by partitioning with EtOAc, followed by silica gel chromatography. Further purification with reversed-phase high-performance liquid chromatography led to isolation of four known cytotoxic compounds, 14-deoxyandrographolide, andrographolide, neoandrographolide and deoxyandrographiside. Among them, andrographolide had the greatest cytotoxicity and tumor specificity, also inducing caspase-3 activation of HSC-2 oral squamous cell carcinoma cells. The present study identified andrographolide as a major antitumor principle in the methanolic extract of leaves of A. paniculata. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Role of human papillomavirus in oral squamous cell carcinoma and oral potentially malignant disorders: A review of the literature

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Gupta, Shikha; Gupta, Sunita

2015-01-01

Human papillomaviruses (HPVs) are epitheliotropic viruses with an affinity for keratinocytes and are principally found in the anogenital tract, urethra, skin, larynx, tracheobronchial and oral mucosa. On the basis of high, but variable frequency of HPV in oral squamous cell carcinoma (OSCC), malignant potential of HPV infection has been hypothesized but not definitely confirmed. The aim of this review was to highlight the genomic structure and possible mechanism of infection and carcinogenesis by HPV in the oral mucosa and to review the frequency of HPV prevalence in OSCC and oral potentially malignant disorders. A computer database search was performed through the use of PubMed from 1994 to 2014. Search keywords used were: HPV and oral cancer, HPV and oral leukoplakia, HPV and oral lichen planus, HPV and OSCC, HPV and verrucous carcinoma, HPV and proliferative verrucous leukoplakia, HPV and oral papilloma. PMID:26097339

Clinico-pathological study on non-squamous cell carcinomas of the oral cavity and oropharynx

International Nuclear Information System (INIS)

Chijiwa, Hideki; Sakamoto, Kikuo; Umeno, Hirohito; Nakashima, Tadashi; Suzuki, Gen; Hayabuchi, Naohumi

2007-01-01

We reviewed 22 cases of non-squamous cell carcinoma (NSCC) of the oral cavity and oropharynx that were treated at the Kurume University Hospital between 1976 and 2005. Two percent of the oral carcinomas and 5% of the oropharyngeal carcinomas were NSCCs. The 5-year and 10-year survival rates of NSCC in the oropharynx were 90%. There was no statistically significant difference in survival rate between squamous cell carcinoma (SCC) and NSCC (p=0.06). The 5-year and 10-year survival rates of NSCC in the oral cavity were 75% and 37%, respectively. There was no statistically significant difference in the survival rate between SCC and NSCC. Survival results well correlated with clinical stages. A significant difference between Stage I, II and III versus Stage IV was found (p=0.04). In contrast, no significant relationship was found between survival and histologic type, or between survival and treatment. Patients with adenoid cystic carcinoma of Grade III, peri-neural invasion or vessel invasion, are recommended to receive adjuvant therapy. (author)

A retrospective analysis of preoperative staging modalities for oral squamous cell carcinoma.

Science.gov (United States)

Kähling, Ch; Langguth, T; Roller, F; Kroll, T; Krombach, G; Knitschke, M; Streckbein, Ph; Howaldt, H P; Wilbrand, J-F

2016-12-01

An accurate preoperative assessment of cervical lymph node status is a prerequisite for individually tailored cancer therapies in patients with oral squamous cell carcinoma. The detection of malignant spread and its treatment crucially influence the prognosis. The aim of the present study was to analyze the different staging modalities used among patients with a diagnosis of primary oral squamous cell carcinoma between 2008 and 2015. An analysis of preoperative staging findings, collected by clinical palpation, ultrasound, and computed tomography (CT), was performed. The results obtained were compared with the results of the final histopathological findings of the neck dissection specimens. A statistical analysis using McNemar's test was performed. The sensitivity of CT for the detection of malignant cervical tumor spread was 74.5%. The ultrasound obtained a sensitivity of 60.8%. Both CT and ultrasound demonstrated significantly enhanced sensitivity compared to the clinical palpation with a sensitivity of 37.1%. No significant difference was observed between CT and ultrasound. A combination of different staging modalities increased the sensitivity significantly compared with ultrasound staging alone. No significant difference in sensitivity was found between the combined use of different staging modalities and CT staging alone. The highest sensitivity, of 80.0%, was obtained by a combination of all three staging modalities: clinical palpation, ultrasound and CT. The present study indicates that CT has an essential role in the preoperative staging of patients with oral squamous cell carcinoma. Its use not only significantly increases the sensitivity of cervical lymph node metastasis detection but also offers a preoperative assessment of local tumor spread and resection borders. An additional non-invasive cervical lymph node examination increases the sensitivity of the tumor staging process and reduces the risk of occult metastasis. Copyright © 2016 European

A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

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Win Kyaw Phyu

Full Text Available Enterovirus A71 (EV-A71 causes self-limiting, hand-foot-and-mouth disease (HFMD that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia, acinar cells (salivary gland, lacrimal gland, lymphoid cells (lymph node, spleen, and muscle fibres (skeletal, cardiac and smooth muscles, liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

O-GlcNAcylation in oral squamous cell carcinoma.

Science.gov (United States)

Kongkaew, Tassaporn; Aung, Win Pa Pa; Supanchart, Chayarop; Makeudom, Anupong; Langsa-Ard, Sarawat; Sastraruji, Thanapat; Chaiyarit, Ponlatham; Krisanaprakornkit, Suttichai

2018-03-01

Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc). However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC). Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading. Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFR tyr1173 , and anti-phosphorylated-Akt ser473 antibodies following standard immunohistochemistry. The immunohistochemical (IHC) score was determined using the Fromowitz standard. Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody. The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFR tyr1173 and phosphorylated-Akt ser473 were significantly higher in OSCC than normal tissues (P O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ. In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFR tyr1173 and phosphorylated-Akt ser473 (P O-GlcNAc or OGT were not determined to correlate with histological grading. Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detection of human papilloma virus (HPV and human immunodeficiency virus (HIV in oral squamous cell carcinoma: A polymerized chain reaction (PCR study

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Suresh Dirasantchu

2015-01-01

Full Text Available Aims and Objectives: Certain strains of human papillomavirus (HPV have been shown to be etiologically related to the development of uterine, cervical, and other genital cancers, but their role in the development of malignancies at other sites is less well established. Previous studies have shown HPV in tumors of the head and neck, but its prevalence has varied depending on the detection methods and the types of tumor and/or tissue examined. This study was undertaken for the detection of high-risk HPV types 16 and 18 and human immunodeficiency virus (HIV in oral squamous cell carcinoma. Materials and Methods: Twenty-five patients histologically diagnosed with oral squamous cell carcinoma and 10 apparently normal persons as controls were selected for the present study. Two biopsy specimens were removed surgically by incision biopsy for histopathological examination and polymerized chain reaction (PCR study. Results: Out of 25 oral squamous cell carcinoma subjects, 8 were found to be HPV positive in PCR. Out of these eight subjects, four had HPV 16 and the other four had other genotypes, and one subject was HIV positive. Conclusion: The conclusion drawn from the present study was that well-defined risk factors like HPV may play a prominent role in the development of oral squamous cell carcinomas, in addition to other risk factors. Further studies with a larger sample size are necessary to arrive at conclusions and to explore the relationship of HPV and HIV in oral squamous cell carcinoma.

The relationship between histopathological findings in oral squamous cell carcinoma and FDG uptake on PET

International Nuclear Information System (INIS)

Izumisawa, Mitsuru; Shozushima, Masanori; Sato, Hirotaka

2003-01-01

It is known that, in fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) for the diagnosis of oral cancer, FDG uptake may vary even among different cases of the same squamous cell carcinoma. However, the details of this phenomenon have not yet been elucidated. In this study, we analyzed the relationship between histopathological findings in oral squamous cell cancer and PET findings on FDG uptake. We examined 45 patients with oral squamous cell carcinoma who had undergone FDG PET before treatment. FDG uptake was assessed by a standardized uptake value (SUV) calculated according to the PET-measured tissue concentration of FDG, the administered dose of radionuclide, and the body weight of the patient. The relationship between the mean SUV and each of the following parameters was examined: histological grade of malignancy, degree of cell differentiation, size and/or local extent of the primary lesion, and cell density of the tumor. The mean SUV of FDG uptake did not depend on the histological grade of malignancy or on the degree of cell differentiation, but tended to be greater the larger the primary lesion. SUV also depended on cell density, increasing with the percentage of tumor parenchyma. It is concluded that cancer cell density greatly influences the SUV of FDG, in that a tumor with fewer cellular elements in cancer tissue tends to become a false negative. (author)

The role of human papillomavirus in oral squamous cell carcinoma: myth and reality.

Science.gov (United States)

Kansy, Katinka; Thiele, Oliver; Freier, Kolja

2014-06-01

As the traditional risk factors for oral squamous cell carcinoma, especially tobacco, decline, new potential causative agents become the focus of research. Since the discovery of human papillomavirus (HPV) and its importance in carcinogenesis in cervical cancer, a lot of research has been undertaken to define its role in different types of cancer. In the present study, we evaluate the role of high-risk HPV types in initiation and progression of oral squamous cell carcinoma (OSCC) using a systematic review of the current literature. A literature research with the search term "HPV oral squamous cell carcinoma" was performed via PubMed. Results were screened systematically for relevance and classified into the following categories: molecular biology, genetics, clinical aspects, and prevalence. Articles were then further analyzed to assess quality. The literature research led to 527 results, with an overall HPV prevalence of 30.1 % in OSCCs. The most frequently identified subtypes were HPV-16 and HPV-18 (25.4 and 18.1 %, respectively). Prognostic relevance of HPV was discussed controversially. HPV detection via polymerase chain reaction is the most established method today. Molecular changes according to carcinogenic pathways described for cervix carcinoma were not routinely found in OSCC. In general, no definite role of high-risk HPV is currently deducible from the literature. High-risk subtypes 16 and 18 are present in the genome in approximately one third of OSCC. Its role as a causative agent is less clear than the role in oropharyngeal tumors. The infection might not be the cause of carcinogenesis in a significant number of patients but may become proportionally more important with the decrease of the classical risk factors of tobacco and alcohol.

An in vivo cytogenetic analysis of human oral squamous cell carcinoma

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Abhimanyu Mohanta

2015-01-01

Full Text Available Background: Oral cancer ranks in the top three of all cancers in India, which accounts for over 30% of all cancers reported in the country. The micronucleus test (MNT is one of the most widely applied short term tests used in genetic toxicology to evaluate the mutagenicity and carcinogenicity. Aims: The present study aims at an in vivo cytogenetic analysis of human oral squamous cell carcinoma and to assess the applicability of MNT in diagnosing early detection of oral carcinoma. Materials and Methods: Exfoliated scrape smears were collected from the clinically diagnosed 136 patients suffering from oral precancerous and cancerous lesions. The wet fixed smears were stained by adopting Papanicolaou's staining protocol and counter-stained with Giemsa's solution. Results: The frequency of micronucleated cells has been observed to be in increasing order with the increase of the age-groups and from control to precancerous to cancerous cases significantly in both sexes. Conclusion: Micronucleus formation in the oral mucosa could be a biomarker of genetic damage and also a potential onco-indicator in the long run of oral carcinogenesis. Therefore, MNT can be applied for the early detection of oral carcinoma in the human being.

Cranberry and Grape Seed Extracts Inhibit the Proliferative Phenotype of Oral Squamous Cell Carcinomas

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Kourt Chatelain

2011-01-01

Full Text Available Proanthocyanidins, compounds highly concentrated in dietary fruits, such as cranberries and grapes, demonstrate significant cancer prevention potential against many types of cancer. The objective of this study was to evaluate cranberry and grape seed extracts to quantitate and compare their anti-proliferative effects on the most common type of oral cancer, oral squamous cell carcinoma. Using two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC25, assays were performed to evaluate the effects of cranberry and grape seed extract on phenotypic behaviors of these oral cancers. The proliferation of both oral cancer cell lines was significantly inhibited by the administration of cranberry and grape seed extracts, in a dose-dependent manner. In addition, key regulators of apoptosis, caspase-2 and caspase-8, were concomitantly up-regulated by these treatments. However, cranberry and grape seed extracts elicited differential effects on cell adhesion, cell morphology, and cell cycle regulatory pathways. This study represents one of the first comparative investigations of cranberry and grape seed extracts and their anti-proliferative effects on oral cancers. Previous findings using purified proanthocyanidin from grape seed extract demonstrated more prominent growth inhibition, as well as apoptosis-inducing, properties on CAL27 cells. These observations provide evidence that cranberry and grape seed extracts not only inhibit oral cancer proliferation but also that the mechanism of this inhibition may function by triggering key apoptotic regulators in these cell lines. This information will be of benefit to researchers interested in elucidating which dietary components are central to mechanisms involved in the mediation of oral carcinogenesis and progression.

The role of oxidative stress and periodontal disease in squamous cell carcinomas of the oral cavity – a review

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Simina Boia1,

2016-12-01

Full Text Available OBJECTIVES AND BACKGROUND This multidisciplinary and retrospective study of the Periodontal, Ear nose and throat, Oral-Maxillofacial and Biochemical literature aims, highlights and recalls the important role of the oxidative stress (OS and periodontal disease in the development of squamous cell carcinomas of the oral cavity (OSCC. MATERIALS AND METHODS In the present study we analyzed a total number of 670 cases, collected from specialized scientific papers belonging to several authors of international level. These scientific papers are focused on highlighting the most common lipid peroxidation marker, Malondialdehyde (MDA, of both periodontal disease and squamous cell carcinoma of the oral cavity from serum or saliva samples that are biochemically collected and analyzed. RESULTS In all analyzed studies, we found that oxidative stress alters the composition of saliva. Also the depletion of antioxidants was remarked in the groups of subjects diagnosed with OSCC and those affected by periodontal disease. Scientific studies that investigated smokers, revealed the fact that these patients also show increased levels of reactive oxygen species. Thus, it is very likely that oxidative damage is intensified by smoking. CONCLUSIONS The purpose of this review was to emphasize the importance of oxidative stress in the development of periodontal disease as a first stage towards the development of squamous cell carcinomas and to represent the essential foundation of more extensive future investigations. REFERENCES 1. Rashmi M, Saumya B. Evaluation of salivary and serum lipid peroxidation, and glutathione in oral leukoplakia and oral squamous cell carcinoma. Journal of Oral Science. 2014;56:135-142. 2. Tóthová L, Kamodyová N, Červenka T, Celec P. Salivary markers of oxidative stress in oral diseases. Front. Cell. Infect. Microbiol. 2015. 3. Bahar G, Feinmesser R, Shpitzer T, Popovtzer A, Nagler RM, Salivary analysis in oral cancer patients: DNA and protein

Oral squamous cell carcinoma and a clinically negative neck : the value of follow-up

NARCIS (Netherlands)

Wensing, Bart M; Merkx, Matthias A W; Krabbe, Paul F M; Marres, Henri A M; Van den Hoogen, Frank J A

2011-01-01

BACKGROUND: In squamous cell carcinoma of the oral cavity (SCCOC), regular follow-up comprises 5 years of prescheduled visits, irrespective of tumor stage/classification and/or treatment. We analyzed our standard treatment and follow-up protocol in patients with a preoperative clinically negative

A comparative study on the mast cells count in oral squamous cell carcinoma and normal oral mucosa

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Mahsa Dastpak

2015-03-01

Full Text Available Introduction: Oral squamous cell carcinoma (OSCC is one of the 10 most common malignant tumors and SCC accounts 94% of all oral malignancies. Mast cells are regarded as complex and multifunctional cells, playing a significant role in immunopathology . The aim of this study is to evaluate the number of mast cells in tissue sections of oral squamous cell carcinoma (OSCC in comparison with normal mucosa. Materials & Methods: Sixty paraffin-embedded specimens were obtained from the archives of the Department of Oral and Maxillofacial Pathology,dental school of Babol university of medical science (15 high grade,15 low grade and 30 Iritation Fibroma. Classification of OSCC cases was according to the BRODER`S malignancy grading system. Hematoxylin and Eosin-stained slides were re-evaluated before entering the samples in our study. Toluidine blue(1% staining was used to identify Mast cells in samples . We used SPSS software version 18 and one way ANOVA test for analyzing data. Results: The highest mast cell count was seen in normal tissue and it was higher in low grade OSCC in comparison with high grade, but the differences between groups weren’t statistically significant. The Mean count of mast cell between OSCC and normal oral mucosa was statistically significant different(p=0.019.We didn’t observe any statistically significant difference between Mast cell counts of control group and low grade OSCC . The same result was seen between high garde and low grade OSCC . The Mean mast cell count difference between male and female groups weren’t statistically significant. The Mean mast cell count difference between high grade OSCC and control group was significant (p<0.05. Conclusion: According to the results, the average amount of mast cells decreased in OSCC in comparison with normal oral mucosa . It does not seem that mast cells play an important role in tumor progression, although further study is needed. 

microRNA-188 is downregulated in oral squamous cell carcinoma and inhibits proliferation and invasion by targeting SIX1.

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Wang, Lili; Liu, Hongchen

2016-03-01

microRNA-188 expression is downregulated in several tumors. However, its function and mechanism in human oral squamous cell carcinoma (OSCC) remains obscure. The present study aims to identify the expression pattern, biological roles, and potential mechanism by which miR-188 dysregulation is associated with oral squamous cell carcinoma. Significant downregulation of miR-188 was observed in OSCC tissues compared with paired normal tissues. In vitro, gain-of-function, loss-of-function experiments were performed to examine the impact of miR-188 on cancer cell proliferation, invasion, and cell cycle progression. Transfection of miR-188 mimics suppressed Detroit 562 cell proliferation, cell cycle progression and invasion, with downregulation of cyclin D1, MMP9, and p-ERK. Transfection of miR-188 inhibitor in FaDu cell line with high endogenous expression exhibited the opposite effects. Using fluorescence reporter assays, we confirmed that SIX1 was a direct target of miR-188 in OSCC cells. Transfection of miR-188 mimics downregulated SIX1 expression. SIX1 siRNA treatment abrogated miR-188 inhibitor-induced cyclin D1 and MMP9 upregulation. In addition, we found that SIX1 was overexpressed in 32 of 80 OSCC tissues. In conclusion, this study indicates that miR-188 downregulation might be associated with oral squamous cell carcinoma progression. miR-188 suppresses proliferation and invasion by targeting SIX1 in oral squamous cell carcinoma cells.

Risk factors for and consequences of inadequate surgical margins in oral squamous cell carcinoma

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Lawaetz, Mads; Homøe, Preben

2014-01-01

OBJECTIVE: The purpose of this study was to examine which factors are associated with inadequate surgical margins and to assess the postoperative consequences. STUDY DESIGN: A retrospective cohort of 110 patients with oral squamous cell carcinoma treated with surgery during a 2-year period...

A reverse Warburg metabolism in oral squamous cell carcinoma is not dependent upon myofibroblasts

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Jensen, David Hebbelstrup; Therkildsen, Marianne Hamilton; Dabelsteen, Erik

2015-01-01

expression of MCT-4 have been shown to have prognostic importance, primarily in patients with breast cancer. However, this phenomenon has only scarcely been described in oral squamous cell carcinoma (OSCC). Given the prognostic importance of myofibroblasts in OSCC, we also examined a potential relationship...

Circulating miRNAs as biomarkers for oral squamous cell carcinoma recurrence in operated patients

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Yan, Yan; Wang, Xuan; Venø, Morten Trillingsgaard

2017-01-01

MicroRNAs (miRNAs) are small regulatory non-coding RNAs for which altered expression in cancers can serve as potential biomarkers for diseases. We here investigated whether circulating miRNAs can serve as biomarkers for predicting post-operational recurrence of oral squamous cell carcinoma (OSCC...

Oral squamous cell carcinoma arising in a patient after hematopoietic stem cell transplantation with bisphosphonate-related osteonecrosis of the jaws.

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Arduino, Paolo G; Scully, Crispian; Chiusa, Luigi; Broccoletti, Roberto

2015-01-01

A 55-year-old man with a history of acute myeloid leukaemia treated with hematopoietic stem cell transplantation and with a 5-year history of bisphosphonate-related osteonecrosis of the jaws, following 12 cycles of intravenous zoledronic acid therapy, presented in December 2009 with a history of increasingly severe unilateral lower jaw pain. Oral examination revealed, as previously, exposed bone in the left mandible, but also a new exophytic mass on the lower-left buccal mucosa. Biopsy confirmed a diagnosis of oral squamous cell carcinoma. To the best of our knowledge, this is the first report of an oral squamous cell carcinoma that appeared adjacent to an area of osteochemonecrosis.

Decreased expression of cell adhesion genes in cancer stem-like cells isolated from primary oral squamous cell carcinomas.

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Mishra, Amrendra; Sriram, Harshini; Chandarana, Pinal; Tanavde, Vivek; Kumar, Rekha V; Gopinath, Ashok; Govindarajan, Raman; Ramaswamy, S; Sadasivam, Subhashini

2018-05-01

The goal of this study was to isolate cancer stem-like cells marked by high expression of CD44, a putative cancer stem cell marker, from primary oral squamous cell carcinomas and identify distinctive gene expression patterns in these cells. From 1 October 2013 to 4 September 2015, 76 stage III-IV primary oral squamous cell carcinoma of the gingivobuccal sulcus were resected. In all, 13 tumours were analysed by immunohistochemistry to visualise CD44-expressing cells. Expression of CD44 within The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma RNA-sequencing data was also assessed. Seventy resected tumours were dissociated into single cells and stained with antibodies to CD44 as well as CD45 and CD31 (together referred as Lineage/Lin). From 45 of these, CD44 + Lin - and CD44 - Lin - subpopulations were successfully isolated using fluorescence-activated cell sorting, and good-quality RNA was obtained from 14 such sorted pairs. Libraries from five pairs were sequenced and the results analysed using bioinformatics tools. Reverse transcription quantitative polymerase chain reaction was performed to experimentally validate the differential expression of selected candidate genes identified from the transcriptome sequencing in the same 5 and an additional 9 tumours. CD44 was expressed on the surface of poorly differentiated tumour cells, and within the The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma samples, its messenger RNA levels were higher in tumours compared to normal. Transcriptomics revealed that 102 genes were upregulated and 85 genes were downregulated in CD44 + Lin - compared to CD44 - Lin - cells in at least 3 of the 5 tumours sequenced. The upregulated genes included those involved in immune regulation, while the downregulated genes were enriched for genes involved in cell adhesion. Decreased expression of PCDH18, MGP, SPARCL1 and KRTDAP was confirmed by reverse transcription quantitative polymerase chain reaction. Lower expression of

Carvacrol suppresses proliferation and invasion in human oral squamous cell carcinoma

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Dai W

2016-04-01

Full Text Available Wei Dai,1,2 Changfu Sun,1,2 Shaohui Huang,1,2 Qing Zhou1,21Department of Oromaxillofacial-Head and Neck Surgery, 2Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaAbstract: Carvacrol, a component of thyme oil, as a novel antitumor agent, has been implicated in several types of cancer cells. However, the mechanisms underlying the effect of carvacrol in human oral squamous cell carcinoma (OSCC remain unclear. Here, we report that carvacrol significantly inhibits tumor cell proliferation, metastasis and invasion, and induces apoptosis in OSCC. Our results demonstrated that the molecular mechanisms of the effect of carvacrol in Tca-8113 induces G1/S cell cycle arrest through downregulation of CDK regulator CCND1 and CDK4, and upregulation of CDK inhibitor P21. Further analysis demonstrated that carvacrol also inhibited Tca-8113 cells’ clone formation in clonogenic cell survival assay. Student’s t-test (two-tailed was used to compare differences between groups, and the significance level was P<0.01. Then, treatment of Tca-8113 cells with carvacrol resulted in downregulation of Bcl-2, Cox2, and upregulation of Bax. Carvacrol significantly inhibited the migration and invasion of human OSCC cells by blocking the phosphorylation of FAK and MMP-9 and MMP-2, transcription factor ZEB1, and β-catenin proteins’ expression. Taken together, these results provide novel insights into the mechanism of carvacrol and suggest potential therapeutic strategies for human OSCC.Keywords: carvacrol, proliferation, metastasis and invasion, oral squamous cell carcinoma

Outcome and histopathologic regression in oral squamous cell carcinoma after preoperative radiochemotherapy

International Nuclear Information System (INIS)

Driemel, Oliver; Ettl, Tobias; Reichert, Torsten E.; Koelbl, Oliver; Dresp, Bernd V.; Reuther, Juergen; Pistner, Hans

2009-01-01

Background and purpose: preoperative radiochemotherapy has been reported to enhance tumor response and to improve long-term survival in advanced squamous cell carcinoma of the head and neck. This retrospective study evaluates regression rate and long-term survival in 228 patients with primary oral squamous cell carcinoma treated by neoadjuvant radiochemotherapy and radical surgery. Patients and methods: all patients with biopsy-proven, resectable oral squamous cell carcinoma - TNM stages II-IV without distant metastasis - received preoperative treatment consisting of fractioned irradiation of the primary and the regional lymph nodes with a total dose of 40 Gy and additional cisplatin (n = 160) or carboplatin (n = 68) during the 1st week of treatment. Radical surgery and neck dissection followed after a delay of 10-14 days. The study only included cases with histologically negative resection margins. Results: after a median follow-up of 5.2 years, 53 patients (23.2%) had experienced local-regional recurrence. The median 2-year disease-specific survival (DSS) rate was 86.2%. 5-year DSS and 10-year DSS were 76.3% and 66.7%, respectively. Complete histological local tumor regression after surgery (ypTO) was observed in 50 patients (21.9%) and was independent of pretreatment tumor classification. Uni- and multivariate survival analysis revealed that ypT- and ypN-stage were the most decisive predictors for DSS. Conclusion: preoperative radiochemotherapy with cisplatin/carboplatin followed by radical surgery attains favorable long-term survival rates. This applies especially to cases with complete histological tumor regression after radiochemotherapy, which can be assumed for one of five patients. (orig.)

Freeze-Dried Black Raspberries in Preventing Oral Cancer Recurrence in High-Risk Appalachian Patients Previously Treated With Surgery For Oral Cancer

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2018-03-04

Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Contemporary Diagnostic Imaging of Oral Squamous Cell Carcinoma – A Review of Literature

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Pałasz, Paulina; Adamski, Łukasz; Górska-Chrząstek, Magdalena; Starzyńska, Anna; Studniarek, Michał

2017-01-01

Summary Oral squamous cell carcinoma (OSCC) is the most common cancer of the oral cavity and constitutes 95% of all cancers of this area. Men are affected twice as commonly as women, primarily if they are over 50 years of age. Forty percent of the lesions are localized in the tongue and 30% in the floor of the oral cavity. OSCC often affects upper and lower gingiva, buccal mucous membrane, the retromolar triangle and the palate. The prognosis is poor and the five-year survival rate ranges from 20% (OSCC in the floor of the mouth) to 60% (OSCC in the alveolar part of the mandible). Treatment is difficult, because of the localization and the invasiveness of the available methods. The diagnosis is made based on a histopathological examination of a biopsy sample. The low detection rate of early oral SCC is a considerable clinical issue. Although the oral cavity can be easily examined, in the majority of cases oral SCC is diagnosed in its late stages. It is difficult to diagnose metastases in local lymph nodes and distant organs, which is important for planning the scope of resection and further treatment, graft implantation, and differentiation between reactive and metastatic lymph nodes as well as between disease recurrence and scars or adverse reactions after surgery or radiation therapy. Imaging studies are performed as part of the routine work-up in oral SCC. However, it is difficult to interpret the results at the early stages of the disease. The following imaging methods are used – dental radiographs, panoramic radiographs, magnetic resonance imaging with diffusion-weighted and dynamic sequences, perfusion computed tomography, cone beam computed tomography, single-photon emission computed tomography, hybrid methods (PET/CT, PET/MRI, SPECT/CT) and ultrasound. Some important clinical problems can be resolved with the use of novel modalities such as MRI with ADC sequences and PET. The aim of this article is to describe oral squamous cell carcinoma as it appears in

Extensive Myiasis infestation associated with Oral Squamous Cell Carcinoma: Report of two cases

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Sudharani Biradar

2015-01-01

Full Text Available Myiasis is the condition of infestation of the body by fly larvae (maggots. The deposited eggs develop into larvae, which penetrate deep structures causing adjacent tissue destruction. It is an uncommon clinical condition, being more frequent in tropical countries and hot climate regions, and associated with poor hygiene, suppurative oral lesions, alcoholism and senility. The diagnosis of Myiasis is basically made by the presence of larvae. The reported cases of oral Myiasis associated with oral cancer in the literature are few. This paper reports two cases of oral and maxillofacial Myiasis involving larvae in patients with squamous cell carcinoma in adult males. The condition was managed by manual removal of the larvae, one by one, with the help of forceps and subsequent management through proper health care.

Immunohistochemical Analysis Using Antipodocalyxin Monoclonal Antibody PcMab-47 Demonstrates Podocalyxin Expression in Oral Squamous Cell Carcinomas.

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Itai, Shunsuke; Yamada, Shinji; Kaneko, Mika K; Harada, Hiroyuki; Kato, Yukinari

2017-10-01

Podocalyxin is a CD34-related type I transmembrane protein that is highly glycosylated with N-glycan, O-glycan, and keratan sulfate. Podocalyxin was originally found in the podocytes of rat kidney and is reportedly expressed in many types of tumors, including brain tumors, colorectal cancers, and breast cancers. Overexpression of podocalyxin is an independent predictor of progression, metastasis, and poor outcome. We recently immunized mice with recombinant human podocalyxin, which was produced using LN229 glioblastoma cells, and produced a novel antipodocalyxin monoclonal antibody (mAb), PcMab-47, which reacts with endogenous podocalyxin-expressing cancer cell lines and normal cell lines independent of glycosylation in Western blot, flow cytometry, and immunohistochemical analyses. In this study, we performed immunohistochemical analysis against oral cancers using PcMab-47. PcMab-47-stained oral squamous cell carcinoma cells in a cytoplasmic pattern and detected 26/38 (68.4%) of oral squamous cell carcinoma cells on tissue microarrays. These results indicate that PcMab-47 is useful in detecting podocalyxin of oral cancers for immunohistochemical analysis.

Gingival squamous cell carcinoma

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Amit Walvekar

2017-01-01

Full Text Available Oral squamous cell carcinoma (OSCC is the most common epithelial malignancy affecting the oral cavity. The most common sites for the development are lateral surface of tongue and floor of mouth; the least common sites are soft palate, gingiva, and buccal mucosa. Gingival squamous cell carcinoma can mimic a multitude of oral lesions and enlargements, especially those of inflammatory origin. In addition, predisposing and presenting factors are different from those of other OSCCs. Careful examination as well as routine biopsy are crucial for accurate diagnosis.

Expression of E-cadherin and β-catenin in basaloid and conventional squamous cell carcinoma of the oral cavity: are potential prognostic markers?

International Nuclear Information System (INIS)

Hanemann, João Adolfo Costa; Oliveira, Denise Tostes; Nonogaki, Suely; Nishimoto, Inês Nobuko; Carli, Marina Lara de; Landman, Gilles; Kowalski, Luiz Paulo

2014-01-01

Basaloid squamous cell carcinoma presents with a preference for the head and neck region, and shows a distinct aggressive behavior, with frequent local recurrences, regional and distant metastasis. The alterations in the cadherin-catenin complex are fundamental requirements for the metastasis process, and this is the first study to evaluate the immunostaining of E-cadherin and β-catenin in oral basaloid squamous cell carcinoma. Seventeen cases of this tumor located exclusively in the mouth were compared to 26 cases of poorly differentiated squamous cell carcinoma and 28 cases of well to moderately differentiated squamous cell carcinoma matched by stage and tumor site. The immunostaining of E-cadherin and β-catenin were evaluated in the three groups and compared to their clinicopathological features and prognosis. For groups poorly differentiated squamous cell carcinoma and basaloid squamous cell carcinoma, reduction or absence of E-cadherin staining was observed in more than 80.0% of carcinomas, and it was statistically significant compared to well to moderately differentiated squamous cell carcinoma (p = .019). A strong expression of β-catenin was observed in 26.9% and 20.8% of well to moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma, respectively, and in 41.2% of basaloid squamous cell carcinoma. The 5-year and 10-year overall and disease-free survival rates demonstrated no significant differences among all three groups. The clinical and biological behavior of three groups of the oral cavity tumors evaluated are similar. E-cadherin and β-catenin immunostaining showed no prognostic value for basaloid and conventional squamous cell carcinomas

Expression of E-cadherin and β-catenin in basaloid and conventional squamous cell carcinoma of the oral cavity: are potential prognostic markers?

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Hanemann, João Adolfo Costa; Oliveira, Denise Tostes; Nonogaki, Suely; Nishimoto, Inês Nobuko; de Carli, Marina Lara; Landman, Gilles; Kowalski, Luiz Paulo

2014-06-03

Basaloid squamous cell carcinoma presents with a preference for the head and neck region, and shows a distinct aggressive behavior, with frequent local recurrences, regional and distant metastasis. The alterations in the cadherin-catenin complex are fundamental requirements for the metastasis process, and this is the first study to evaluate the immunostaining of E-cadherin and β-catenin in oral basaloid squamous cell carcinoma. Seventeen cases of this tumor located exclusively in the mouth were compared to 26 cases of poorly differentiated squamous cell carcinoma and 28 cases of well to moderately differentiated squamous cell carcinoma matched by stage and tumor site. The immunostaining of E-cadherin and β-catenin were evaluated in the three groups and compared to their clinicopathological features and prognosis. For groups poorly differentiated squamous cell carcinoma and basaloid squamous cell carcinoma, reduction or absence of E-cadherin staining was observed in more than 80.0% of carcinomas, and it was statistically significant compared to well to moderately differentiated squamous cell carcinoma (p = .019). A strong expression of β-catenin was observed in 26.9% and 20.8% of well to moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma, respectively, and in 41.2% of basaloid squamous cell carcinoma. The 5-year and 10-year overall and disease-free survival rates demonstrated no significant differences among all three groups. The clinical and biological behavior of three groups of the oral cavity tumors evaluated are similar. E-cadherin and β-catenin immunostaining showed no prognostic value for basaloid and conventional squamous cell carcinomas.

Applicability of preoperative nuclear morphometry to evaluating risk for cervical lymph node metastasis in oral squamous cell carcinoma.

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Masaaki Karino

Full Text Available BACKGROUND: We previously reported the utility of preoperative nuclear morphometry for evaluating risk for cervical lymph node metastases in tongue squamous cell carcinoma. The risk for lymph node metastasis in oral squamous cell carcinoma, however, is known to differ depending on the anatomical site of the primary tumor, such as the tongue, gingiva, mouth floor, and buccal mucosa. In this study, we evaluated the applicability of this morphometric technique to evaluating the risk for cervical lymph node metastasis in oral squamous cell carcinoma. METHODS: A digital image system was used to measure the mean nuclear area, mean nuclear perimeter, nuclear circular rate, ratio of nuclear length to width (aspect ratio, and nuclear area coefficient of variation (NACV. Relationships between these parameters and nodal status were evaluated by t-test and logistic regression analysis. RESULTS: Eighty-eight cases of squamous cell carcinoma (52 of the tongue, 25 of the gingiva, 4 of the buccal mucosa, and 7 of the mouth floor were included: 46 with positive node classification and 42 with negative node classification. Nuclear area and perimeter were significantly larger in node-positive cases than in node-negative cases; however, there were no significant differences in circular rate, aspect ratio, or NACV. We derived two risk models based on the results of multivariate analysis: Model 1, which identified age and mean nuclear area and Model 2, which identified age and mean nuclear perimeter. It should be noted that primary tumor site was not associated the pN-positive status. There were no significant differences in pathological nodal status by aspect ratio, NACV, or primary tumor site. CONCLUSION: Our method of preoperative nuclear morphometry may contribute valuable information to evaluations of the risk for lymph node metastasis in oral squamous cell carcinoma.

Association between polymorphisms in pre-miRNA genes and risk of oral squamous cell cancer in a Chinese population.

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Enjiao Zhang

Full Text Available MicroRNAs play important roles in the development of human cancers. This case-control study is to evaluate the roles of the polymorphisms in pre-miRNAs on risk of oral cancer in a Chinese population.The genotypes of three polymorphisms were determined in 340 patients with oral squamous cell cancer and 340 healthy controls who were frequency matched for age and sex. Odds ratios (ORs and 95% confidence intervals (95%CIs were calculated to assess the association. All analyses were performed using the SPSS software. 3.154( 0.001.For miR-499 rs3746444, individuals carrying homozygous CC genotype had increased risks of oral cancer compared with the homozygous wild TT genotype (adjusted OR was 3.154, 95%CI was 1.555-6.397, P value was 0.001. The C allele of miR-499 rs3746444 was associated with a higher risk of oral cancer with significant odds ratio of 1.453. In the stratified analyses by sex, the associations between miR-499 rs3746444 and miR-146a rs2910164 polymorphisms with the susceptibility of oral squamous cell cancer were significant in males. However, with 1/4 as many subjects there were no significant associations between the three polymorphisms and oral cancer risks in females. The joint effects of miRNA polymorphisms and smoking on the risk of OSCC were analyzed and the results suggested that the association between microRNA genetic variants and OSCC risk was modified by smoking.These findings suggest that miR-499 rs3746444 and miR-146a rs2910164 polymorphisms may contribute to genetic susceptibility to oral squamous cell cancer.

The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

International Nuclear Information System (INIS)

He, Di; Chen, Wantao; Xu, Qin; Yan, Ming; Zhang, Ping; Zhou, Xiaojian; Zhang, Zhiyuan; Duan, Wenhu; Zhong, Laiping; Ye, Dongxia

2009-01-01

Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated. Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) in vitro. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA. The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased. The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The

Evidences Suggesting Involvement of Viruses in Oral Squamous Cell Carcinoma

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Gupta, Kanupriya; Metgud, Rashmi

2013-01-01

Oral cancer is one of the most common cancers and it constitutes a major health problem particularly in developing countries. Oral squamous cell carcinoma (OSCC) represents the most frequent of all oral neoplasms. Several risk factors have been well characterized to be associated with OSCC with substantial evidences. The etiology of OSCC is complex and involves many factors. The most clearly defined potential factors are smoking and alcohol, which substantially increase the risk of OSCC. However, despite this clear association, a substantial proportion of patients develop OSCC without exposure to them, emphasizing the role of other risk factors such as genetic susceptibility and oncogenic viruses. Some viruses are strongly associated with OSCC while the association of others is less frequent and may depend on cofactors for their carcinogenic effects. Therefore, the exact role of viruses must be evaluated with care in order to improve the diagnosis and treatment of OSCC. Although a viral association within a subset of OSCC has been shown, the molecular and histopathological characteristics of these tumors have yet to be clearly defined. PMID:24455418

Evidences Suggesting Involvement of Viruses in Oral Squamous Cell Carcinoma

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Kanupriya Gupta

2013-01-01

Full Text Available Oral cancer is one of the most common cancers and it constitutes a major health problem particularly in developing countries. Oral squamous cell carcinoma (OSCC represents the most frequent of all oral neoplasms. Several risk factors have been well characterized to be associated with OSCC with substantial evidences. The etiology of OSCC is complex and involves many factors. The most clearly defined potential factors are smoking and alcohol, which substantially increase the risk of OSCC. However, despite this clear association, a substantial proportion of patients develop OSCC without exposure to them, emphasizing the role of other risk factors such as genetic susceptibility and oncogenic viruses. Some viruses are strongly associated with OSCC while the association of others is less frequent and may depend on cofactors for their carcinogenic effects. Therefore, the exact role of viruses must be evaluated with care in order to improve the diagnosis and treatment of OSCC. Although a viral association within a subset of OSCC has been shown, the molecular and histopathological characteristics of these tumors have yet to be clearly defined.

Frequency of HPV in oral cavity squamous cell carcinoma.

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de Abreu, Priscila Marinho; Có, Anna Clara Gregório; Azevedo, Pedro Leite; do Valle, Isabella Bittencourt; de Oliveira, Karine Gadioli; Gouvea, Sônia Alves; Cordeiro-Silva, Melissa Freitas; Louro, Iúri Drummond; de Podestá, José Roberto Vasconcelos; Lenzi, Jeferson; Sena, Agenor; Mendonça, Elismauro Francisco; von Zeidler, Sandra Lúcia Ventorin

2018-03-27

The prevalence of high-risk human papillomavirus (HPV) DNA in cases of oral cavity squamous cell carcinoma (SCC) varies widely. The aim of this study is to investigate the frequency of high-risk HPV DNA in a large Brazilian cohort of patients with oral cavity SCC. Biopsy and resected frozen and formalin-fixed paraffin-embedded specimens of oral cavity SCC were available from 101 patients who were recruited at two Brazilian centres. Stringent measures with respect to case selection and prevention of sample contamination were adopted to ensure reliability of the data. Nested PCR using MY09/MY11 and GP5 + /GP6 + as well as PGMY09/11 L1 consensus primers were performed to investigate the presence of HPV DNA in the tumours. HPV-positive cases were subjected to direct sequencing. Shapiro-Wilk and Student t test were used to evaluate data normality and to compare the means, respectively. Qualitative variables were analysed by logistic regression. Our results demonstrate that the frequency of high-risk HPV types in oral cavity SCC is very low and is less than 4%. All HPV-positive cases were HPV16. In addition, our results do not show a significant association between the tumour clinical features and the risk factors (tobacco, alcohol and HPV) for oral cavity SCC. In the current study, we observed an overlapping pattern of risk factors that are related to tumour development. This, along with a low frequency of high-risk HPV DNA, supports the findings that HPV is not involved in the genesis of oral cavity SCC in Brazilian population.

Loss of a novel mucin-like epithelial glycoprotein in oral and cervical squamous cell carcinomas

DEFF Research Database (Denmark)

Nielsen, P A; Mandel, U; Therkildsen, M H

1997-01-01

differentiated carcinomas, mainly from cervix, expressed the gp230 epitope. The results suggest that a membrane-bound mucin-like molecule, gp230, is associated with the differentiated phenotype of normal mucosal stratified squamous epithelia and that expression of gp230 generally is lost in severe oral...

A novel Multiple-Marker Method for the Early Diagnosis of Oral Squamous Cell Carcinoma

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Jutta Ries

2009-01-01

Full Text Available Objective: Melanoma associated antigens-A (MAGE-A expression is highly specific to cancer cells. Thus, they can be the most suitable targets for the diagnosis of malignancy. The aim of this study was to evaluate the sensitivity of multiple MAGE-A expression analysis for the diagnosis of oral squamous cell carcinoma (OSCC.

The subclonal structure and genomic evolution of oral squamous cell carcinoma revealed by ultra-deep sequencing

DEFF Research Database (Denmark)

Tabatabaeifar, Siavosh; Thomassen, Mads; Larsen, Martin J

2017-01-01

Recent studies suggest that head and neck squamous cell carcinomas are very heterogeneous between patients; however the subclonal structure remains unexplored mainly due to studies using only a single biopsy per patient. To deconvolutethe clonal structure and describe the genomic cancer evolution......, we applied whole-exome sequencing combined with ultra-deep targeted sequencing on oral squamous cell carcinomas (OSCC). From each patient, a set of biopsies was sampled from distinct geographical sites in primary tumor and lymph node metastasis.We demonstrate that the included OSCCs show a high...

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma

DEFF Research Database (Denmark)

Alkureishi, Lee W T; Burak, Zeynep; Alvarez, Julio A

2009-01-01

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB...

Ursolic Acid Florotriazole Treatment Causes Inhibition of Squamous ...

African Journals Online (AJOL)

observed malignant tumor of mucosa lining of the oral cavity. In Korea squamous cell carcinoma accounts for more than 90 % of the detected malignant tumors of the oral cavity [1]. Despite advancement in the fields of chemotherapy, radiation therapy and surgery, the prognosis of oral squamous cell cancer patients remains ...

Human papillomavirus and oral squamous cell carcinoma: A review of HPV-positive oral squamous cell carcinoma and possible strategies for future.

Science.gov (United States)

Jiang, Shan; Dong, Yong

Oral squamous cell carcinoma (OSCC) is a common cancer worldwide. Besides tobacco use and alcohol consumption, human papillomavirus (HPV) infection has also been identified as a risk factor for OSCC recently. The OSCC incidence has increased in recent years, especially among younger women. The purpose of this article is to review clinical and epidemiological studies on the association between HPV infection and OSCCs, and the efficacy of HPV vaccine, so as to provide possible policy implications for preventing HPV-positive OSCC. It is necessary to review the present related body of knowledge to determine whether the association between HPV infection and OSCC has been thoroughly studied. The study was based on literature review. Studies were identified using electronic databases including MEDLINE, PubMed, EMBASE, etc. The inclusion and exclusion criteria were based on consultation from a panel of experts in this area and carefully designed. Based on a systematic review of literatures, HPV infection is a possible cause for the incidence of HPV-positive OSCCs. The prevalence of HPV infection possibly contributed to the increasing trends of HPV-positive OSCCs. Oral HPV infection is a form of HPV transmission. Oral sex behaviors and open-mouthed kissing are probably reasons for oral HPV infection. We also have some epidemiological evidences proving that HPV vaccine provides a possible solution for preventing oral HPV infection. Increased awareness of HPV-positive OSCCs is essential due to the severity of this problem. Biological and epidemiological data regarding the link between sexual behavior and HPV-associated cancers indicate a probable connection, although definitive data are needed. Future studies are needed to investigate the mechanisms of how HPV infection causes HPV-positive OSCCs, whether HPV vaccine provides a prevention for OSCCs, and other important issues. Copyright © 2017 Elsevier Inc. All rights reserved.

Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational study

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Lajer, C B; Nielsen, F C; Friis-Hansen, L

2011-01-01

MicroRNAs (miRNAs) are small non-coding RNAs, which regulate mRNA translation/decay, and may serve as biomarkers. We characterised the expression of miRNAs in clinically sampled oral and pharyngeal squamous cell carcinoma (OSCC and PSCC) and described the influence of human papilloma virus (HPV)....

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma

DEFF Research Database (Denmark)

Alkureishi, L W T; Burak, Z; Alvarez, J A

2009-01-01

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB...

Successful treatment of oral squamous cell carcinoma with intralesional fluorouracil in a Malayan tapir (Tapirus indicus).

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Miller, C L; Templeton, R S; Karpinski, L

2000-06-01

An oral mass was observed in a Malayan tapir (Tapirus indicus). Squamous cell carcinoma was diagnosed by histologic examination of a biopsy specimen. A series of intralesional injections using fluorouracil resulted in complete regression of the neoplasm with no recognized adverse effects.

Predictive factors of occult neck metastasis in patients with oral squamous cell carcinoma

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Renato Fortes Bittar

Full Text Available ABSTRACT INTRODUCTION: It is well established that cervical lymph node metastasis is the most important prognostic factor in patients with oral squamous cell carcinoma of the upper aerodigestive tract. The definition of parameters and classifications that could separate patients in groups of low, intermediate and high-risk is being attempted for several years. OBJECTIVE: The objective of this study was to determine possible predictive factors related to the occurrence of occult cervical lymph node metastasis through the analysis of histopathological reports of surgical specimens obtained after oral squamous cell carcinoma resection and selective neck dissections of patients initially classified as N0. METHODS: This was a primary, retrospective, observational, case-control study. Histopathological reports were reviewed to determine if some findings were related to the occurrence of occult lymph node metastasis. The events analyzed were oral cavity subsites, pT-stage, muscular infiltration, desmoplasia, vascular emboli, perineural infiltration, tumor thickness and compromised margins. RESULTS: Occult cervical metastasis accounted for 19.10 percent of the cases. Desmoplasia, perineural infiltration, tumor thickness and pT4a stage are predictive factors of occult neck metastasis (p-value = 0.0488, 0.0326, 0.0395, 0.0488, respectively. CONCLUSION: The accurate definition of predictive factors of occult cervical metastasis may guide the selection of patients that should be referred to radiotherapy, avoiding the unnecessary exposure of low-risk patients to radiation and allowing a better regional control of the disease in those of moderate or high risk.

Apoptosis in oral epithelial dysplastic lesions and oral squamous cell carcinoma: A prognostic marker

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Shwetha Nambiar

2016-01-01

Full Text Available Background: Apoptotic index (AI using light microscopy as an indirect measure to assess the significance of apoptosis as a proliferative marker in dysplastic lesions and malignant epithelial lesions of the oral cavity. Aims: (1 To quantify the apoptotic bodies/cells in oral epithelial dysplastic (OED lesions and oral squamous cell carcinoma (OSCC. (2 To measure AI in OED and OSCC. (3 To compare AI in OED and OSCC. Settings and Design: The proposed laboratory-based retrospective study involved the use of hematoxylin and eosin (H and E-stained slides of previously diagnosed OED lesions and OSCC from institutional archives. Materials and Methods: This study constituted 50 cases, each of H and E-stained slides of previously diagnosed cases of OED and OSCC. AI was calculated as the number of apoptotic bodies/cells expressed as a percentage of the total number of nonapoptotic tumor/dysplastic cells counted in each case. Statistical Analysis Used: Nonparametric tests such as Kruskal–Wallis test and Mann–Whitney test were used. Results: There was a statistically significant increase in AI from OED to OSCC (P = 0.000. Conclusions: Further studies need to be undertaken to detect and understand the apoptotic mechanisms in the progression from OED to OSCC.

Single cell migration in oral squamous cell carcinoma - possible evidence of epithelial-mesenchymal transition in vivo

DEFF Research Database (Denmark)

Jensen, David H; Reibel, Jesper; Mackenzie, Ian C

2015-01-01

carcinomas, their relationship has not been examined in detail. METHODS: Paraffin-embedded tissues from 28 patients with oral squamous cell carcinomas were stained with antibodies to cytokeratin, α-SMA, vimentin, E-cadherin, N-cadherin and Twist and evaluated for their expression in relation to invasive...

MiR-206 functions as a tumor suppressor and directly targets K-Ras in human oral squamous cell carcinoma [Retraction

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Lin FO

2016-10-01

Full Text Available The Editor-in-Chief and Publisher of OncoTargets and Therapy have been alerted to unacceptable levels of duplication with another published paper: Zhang D, Ni Z, Xu X, and Xiao J. MiR-32 Functions as a Tumor Suppressor and Directly Targets EZH2 in Human Oral Squamous Cell Carcinoma. Medical Science Monitor. 20:2527–2535, 2014.Accordingly, we retract Lin FO, Yao LJ, Xiao J, Liu DF, and Ni ZY. MiR-206 functions as a tumor suppressor and directly targets K-Ras in human oral squamous cell carcinoma. OncoTargets and Therapy. 2014;7:1583–1591.This Retraction relates to 

Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China

OpenAIRE

Chen, Xingdong; Winckler, Bj?rn; Lu, Ming; Cheng, Hongwei; Yuan, Ziyu; Yang, Yajun; Jin, Li; Ye, Weimin

2015-01-01

Poor oral health has been linked with an increased risk of esophageal squamous cell carcinoma (ESCC). We investigated whether alteration of oral microbiota is associated with ESCC risk. Fasting saliva samples were collected from 87 incident and histopathologicallly diagnosed ESCC cases, 63 subjects with dysplasia and 85 healthy controls. All subjects were also interviewed with a questionnaire. V3-V4 region of 16S rRNA was amplified and sequenced by 454-pyrosequencing platform. Carriage of eac...

Squamous cell carcinoma of the oral tongue and floor of mouth. Evaluation of interstitial radium therapy

International Nuclear Information System (INIS)

Delclos, L.; Lindberg, R.D.; Fletcher, G.H.

1976-01-01

From January 1965, to December 1972, 46 patients with squamous cell carcinoma of the floor of the mouth and 102 patients with squamous cell carcinoma of the oral tongue were treated at M. D. Anderson Hospital and Tumor Institute by interstitial irradiation alone or in combination with external irradiation. Through the years the combination of radiation therapy modalities has been adjusted in an attempt to improve local control, keeping complications to a minimum. In this paper we analyze local control, cause of failure and complications as related to the primary size (T Stage) and radiation therapy techniques employed

Retrospective cohort study of prognostic factors in patients with oral cavity and oropharyngeal squamous cell carcinoma.

Science.gov (United States)

Carrillo, José F; Carrillo, Liliana C; Cano, Ana; Ramirez-Ortega, Margarita C; Chanona, Jorge G; Avilés, Alejandro; Herrera-Goepfert, Roberto; Corona-Rivera, Jaime; Ochoa-Carrillo, Francisco J; Oñate-Ocaña, Luis F

2016-04-01

Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma (SCC) are debated. The purpose of this study was to investigate the association of prognostic factors with oncologic outcomes. Patients with oral cavity and oropharyngeal SCC treated from 1997 to 2012 were included in this retrospective cohort study. Associations of prognostic factors with locoregional recurrence (LRR) or overall survival (OS) were analyzed using the logistic regression and the Cox models. Six hundred thirty-four patients were included in this study; tumor size, surgical margins, and N classification were associated with LRR (p oral cavity and oropharyngeal SCC. © 2015 Wiley Periodicals, Inc.

Three-year follow-up of sentinel node-negative patients with early oral cavity squamous cell carcinoma

DEFF Research Database (Denmark)

Sebbesen, Lars; Bilde, Anders; Therkildsen, Marianne

2014-01-01

2009, 53 consecutive SNB-negative patients with oral cavity squamous cell carcinoma (SCC) T1 to T2 were accrued. Follow-up was done continuously with the most recent examination in October 2011. The location of the sentinel lymph nodes was determined using dynamic and planar lymphoscintigraphy...

Evaluating the Role of Immunological Cells (Tissue Eosinophils and Mast Cells) in Progression of Oral Squamous Cell Carcinoma.

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Saxena, S; Singh, A; Singh, P; Sundaragiri, K S; Sankhla, B; Bhargava, A

2018-04-01

Mast cells and eosinophils are increased in oral squamous cell carcinoma. The significance of such an association has been variably thought to be either a potential diagnostic tool for stromal invasion or as a prognostic indicator. The aim of the study was to study the mast cells and eosinophils between normal oral mucosa, leukoplakia and oral squamous cell carcinoma and to study the significance of mast cells in the progression of the lesion. A retrospective study was done on archival tissue received from January 2015 to December 2015, in the Department of Oral Pathology, RUHS College of Dental Sciences, Jaipur, Rajasthan, India. Seventy (70) cases were studied (30 cases each of leukoplakia and carcinoma and 10 cases of control group), sections were stained with toluidine blue solution to reveal mast cells. Eosinophils were studied in Haematoxylin & Eosin stained sections. Mast cell density significantly increased from: normal mucosa to oral leukoplakia to carcinoma, suggesting a role of the mast cells in the development of these lesions. The higher eosinophil counts in carcinoma group compared to dysplasia group proved that they might have a role in stromal invasion. The assessment of these could become, in the future, useful for therapeutic approaches in this subset of the patient.

Quantitative assessment of myofibroblast in severe dysplasia, microinvasion and oral squamous cell carcinoma: an immunohistochemical study.

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Kapse, Sonam C; Rathod, Nanita; Baad, Rajendra; Mandlik, Jyoti; Sharma, Anupam S; Bommanavar, Sushma

2013-01-01

Myofibroblast are essential for the integrity of human body by virtue of its role in wound healing and pathological organ remodeling. Myofibroblast is a universal cellular component in mammalian lesions, but not a typical component of normal untraumatized tissues. Therefore its presence in abundance in case of cancer is a matter of concern. Tumor microenvironment plays a pivotal role in tumor progression. These so called cancer associated fibroblast or myofibroblast are the major components and occur in stromal tissue during carcinogenesis processes. This study is a quantitative assessment of presence and distribution of myofibroblast in severe dysplasia, microinvasion and oral squamous cell carcinoma (OSCC). Myofibroblast, Vimentin, α-SMA, OSCC, Severe dysplasia, Microinvasion. How to cite this article: Kapse SC, Rathod N, Baad R, Mandlik J, Sharma AS, Bommanavar S. Quantitative Assessment of Myofibroblast in Severe Dysplasia, Microinvasion and Oral Squamous Cell Carcinoma: An Immunohistochemical Study. J Contemp Dent Pract 2013;14(1):34-38. Source of support: Nil Conflict of interest: None declared.

Acacia catechu ethanolic bark extract induces apoptosis in human oral squamous carcinoma cells

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Thangavelu Lakshmi

2017-01-01

Full Text Available Oral cancer is in approximately 30% of all cancers in India. This study was conducted to evaluate the cytotoxic activity of ethanolic extract of Acacia catechu bark (ACB against human squamous cell carcinoma cell line-25 (SCC-25. Cytotoxic effect of ACB extract was determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium Bromide assay. A. catechu extract was treated SCC-25 cells with 25 and 50 μg/mL for 24 h. Apoptosis markers such as caspases-8 and 9, bcl-2, bax, and cytochrome c (Cyt-c were done by RT-PCR. Morphological changes of ACB treated cells were evaluated using acridine orange/ethidium bromide (AO/EB dual staining. Nuclear morphology and DNA fragmentation were evaluated using propidium iodide (PI staining. Further, cell cycle analysis was performed using flow cytometry. A. catechu treatment caused cytotoxicity in SCC-25 cells with an IC50 of 52.09 μg/mL. Apoptotic marker gene expressions were significantly increased on ACB treatment. Staining with AO/EB and PI shows membrane blebbing and nuclear membrane distortion, respectively, and it confirms the apoptosis induction in SCC-25 cells. These results suggest that ACB extract can be used as a modulating agent in oral squamous cell carcinoma.

Neoadjuvant Chemotherapy for Locally Advanced Squamous Carcinoma of Oral Cavity: a Pilot Study.

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Sanambar Sadighi

2015-06-01

Full Text Available To evaluate the effect of adding neoadjuvant chemotherapy to surgery and radiation therapy for locally advanced resectable oral cavity squamous cell carcinoma, 24 patients with T3 or T4a oral cavity squamous cell carcinoma were randomly assigned to surgery alone or Docetaxel, Cisplatin, and 5-FU (TPF induction chemotherapy followed by surgery. All patients were planned to receive chemoradiotherapy after surgery. The primary end-points were organ preservation and progression-free-survival. SPSS version 17 was used for data analysis. Median follow-up was 16 months. The median age of the patients was 62 years old (23-75 years. Man/woman ratio was 1.13. The primary site of the tumor was the tongue in most patients (48%. No significant difference was observed between pathologic characteristics of the two groups. Chemotherapy group showed 16% complete pathologic response to TPF. No significant difference in organ preservation surgery or overall survival was detected. However, the patients in the chemotherapy group had longer progression-free-survival (P=0.014. Surgery followed by chemoradiotherapy with or without TPF induction results in similar survival time. However, progression-free-survival improves with the TPF induction chemotherapy. Studies with more patents and new strategies are recommended to evaluate organ preservation improvement and long-term outcomes.

Quality of life in survivors of squamous cell carcinoma of oral and oropharyngeal patients in karachi

International Nuclear Information System (INIS)

Naqvi, S.U.; Farrukh, M.S.; Begum, K.

2017-01-01

Objectives: To evaluate quality of life (QOL) in patients with squamous cell carcinoma of oral and oropharyngeal region. Methodology: This is prospective longitudinal study was conducted at ENT department Dow University Hospital and Radiotherapy Department KIRAN from November 2012 to November 2015. It included 56 patients of squamous cell carcinoma (SCC) of oral cavity and oropharynx regions who had completed cancer treatment (Wide local excision +/-Neck dissection +/- Radiotherapy). UW QOL questionnaire is taken as the tool to analyze the quality improvement in the domains of pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder, taste, saliva, mood and anxiety. Comparative analysis used to assess all 12 factors associated with cancer patients. A paired t-test was used to compare preoperative and 6 months or more post-operative QOL rating. Results: Six months or more after surgery, 13 patients were lost to follow up and 9 died. 34 patients completed the UW QOL. Cancer Survivors presented overall significantly poorer QOL. QOL improved in the domains of activity, shoulder pain, mood and anxiety. Conclusion: This study recommend Quality of life assessment of oral and oropharyngeal cancers which may contribute to functional, psychological and somatic limitations and likely alter the treatment methodology where cure of cancer is equally good for any modality. This study also identifies that cases of early cancer of oral and oropharyngeal region would not compromise QOL of the patients significantly. (author)

Revisiting the association between candidal infection and carcinoma, particularly oral squamous cell carcinoma.

Science.gov (United States)

Mohd Bakri, Marina; Mohd Hussaini, Haizal; Rachel Holmes, Ann; David Cannon, Richard; Mary Rich, Alison

2010-12-21

Tobacco and alcohol are risk factors associated with cancer of the upper aerodigestive tract, but increasingly the role of infection and chronic inflammation is recognized as being significant in cancer development. Bacteria, particularly Helicobacter pylori, and viruses such as members of the human papilloma virus family and hepatitis B and C are strongly implicated as etiological factors in certain cancers. There is less evidence for an association between fungi and cancer, although it has been recognized for many years that white patches on the oral mucosa, which are infected with Candida, have a greater likelihood of undergoing malignant transformation than those that are not infected. This article reviews the association between the development of oral squamous cell carcinoma in potentially malignant oral lesions with chronic candidal infection and describes mechanisms that may be involved in Candida-associated malignant transformation.

Comparative evaluation of eosinophils in normal mucosa, dysplastic mucosa and oral squamous cell carcinoma with hematoxylin-eosin, Congo red, and EMR1 immunohistochemical staining techniques.

Science.gov (United States)

Kargahi, Neda; Razavi, Sayyed Mohammad; Deyhimi, Parviz; Homayouni, Solmaz

2015-01-01

Oral squamous cell carcinoma is the most common malignant lesion of the oral cavity, and it involves various molecular mechanisms. The development of oral squamous cell carcinoma is influenced by the host immune cells, such as eosinophils. The present study was conducted to compare the presence of eosinophils in normal mucosa, dysplastic mucosa, and oral squamous cell carcinoma by -hematoxylin- eosin staining, Congo red staining, and epidermal growth factor-like (EGF-like) module containing a mucin-like hormone receptor1 (EMR1) immunohistochemical marker. In this cross-sectional study, 60 paraffinized samples were selected, consisting of 20 normal mucosae, 20 dysplastic mucosae, and 20 squamous cell carcinoma samples. After confirmation of the diagnosis, the mean number of eosinophils was evaluated by hematoxylin-eosin, Congo red, and immunohystochemical staining techniques. The data were analyzed by SPSS-10 software using the Kruskal-Wallis and Friedman tests. The results showed that the number of eosinophils in dysplastic mucosa was significantly higher than the number in normal mucosa, and the number of eosinophils in squamous cell carcinoma was significantly higher than the number in dysplastic mucosa in all staining techniques (p<0.001). Moreover, the comparison of staining techniques showed a significantly higher number of eosinophils in EMR1immunohistochemicalmarker than were observed when Congo red and hematoxylin - eosin (H&E) staining techniques were used (p<0.001). It can be argued that eosinophil contributes to the identification of lesions that have a higher potential of malignant transformation. Moreover, eosinophil can be suggested as an indicator in the differentiation of oral lesions in cases with borderline diagnosis and in targeted molecular therapy.

Durvalumab Before Surgery in Treating Patients With Oral Cavity or Oropharynx Cancer

Science.gov (United States)

2017-12-20

Human Papillomavirus Infection; Stage I Oral Cavity Squamous Cell Carcinoma; Stage I Oropharyngeal Squamous Cell Carcinoma; Stage II Oral Cavity Squamous Cell Carcinoma; Stage II Oropharyngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

Clinicopathologic study on the effect of preoperative radiochemotherapy for oral squamous cell carcinoma

International Nuclear Information System (INIS)

Kishimoto, Koji; Mandai, Toshiko; Yao, Mayumi; Ono, Tatsuo; Domae, Shohei; Sasaki, Akira

2008-01-01

Preoperative radiochemotherapy has been carried out for many cases of oral cancers to improve locoregional control. The purpose of this study was to evaluate whether preoperative radiochemotherapy for oral squamous cell carcinomas is beneficial for the patients. A retrospective analysis of 182 patients who had successfully undergone operations at our hospital from April 1982 to March 2001 was performed. Subjects consisted of a preoperative radiochemotherapy group (n=88) and a surgery-only group (n=94). We obtained the following results and conclusions: Preoperative radiochemotherapy for advanced oral squamous cell carcinomas (Stage III, IV) did not contribute to improvement of the survival rate, although it was effective for locoregional control. These results indicated that preoperative radiochemotherapy could decrease the reoperations of recurrences and regional lymph node metastases. Therefore, organ preservations were done in some cases by preoperative radiochemotherapy. The preoperative radiochemotherapy effective group showed a better survival rate than the noneffective group, and the response rate of preoperative radiochemotherapy became an independent predictive factor for the prognosis. The 5-year cause-specific survival rate in Stage III, IV was 88.8% for the effective group and 55.8% for the noneffective group. The cause of death in the noneffective group was mainly local recurrence mostly arising from a deep region of the tumor surgical margin, and 75.0% of the dead cases were cases with mode of invasion 4C or 4D. Therefore, we should consider setting a larger safety margin especially in the deep region of a tumor that is highly invasive and for which radiochemotherapy is not effective. (author)

EGFR status in oral squamous cell carcinoma: comparing immunohistochemistry, FISH and CISH detection in a case series study

OpenAIRE

Bernardes, Vanessa F?tima; Gleber-Netto, Frederico Omar; de Sousa, S?lvia Ferreira; Rocha, Rafael Malagoli; de Aguiar, Maria C?ssia Ferreira

2013-01-01

Objectives To compare the immunohistochemistry (IHC) expression of epidermal growth factor receptor (EGFR) in oral squamous cell carcinomas (OSCC) with the gene amplification evaluated by fluorescence in situ hybridization (FISH) and chromogenic in situ hybridization (CISH) and their association with clinicopathological parameters. Additionally, we tested the sensibility and specificity of CISH in comparison with FISH. Design Case series study Setting Oral surgery and pathology department in ...

Association of preoperative radiation effect with tumor angiogenesis and vascular endothelial growth factor in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Shintani, Satoru; Kiyota, Akihisa; Mihara, Mariko; Nakahara, Yuuji; Terakado, Nagaaki; Ueyama, Yoshiya; Matsumura, Tomohiro

2000-01-01

This study examined the relationship between tumor angiogenesis and the radiation-induced response, evaluated based on pathological changes, in oral squamous cell carcinoma patients treated with preoperative radiation therapy. Forty-one cases of squamous cell carcinoma treated with preoperative radiation therapy were investigated. Tumor angiogenesis was assessed by scoring the intratumor microvessel density (IMVD). Expression of vascular endothelial growth factor (VEGF) was also evaluated before and after preoperative radiotherapy. There was no correlation between IMVD in the specimens before therapy and the pathological response to radiation therapy. However, radiation therapy decreased IMVD in the specimens after therapy. A significant association was observed between VEGF expression and resistance to radiation therapy: only 4 of the 21 patients whose tumors exhibited a high level (2+ or 3+) of VEGF staining experienced a major (3+ or 4+) pathological response to radiation therapy. Furthermore, an increasing level of VEGF expression after radiation therapy was observed in non-effective (0 to 2+) response cases. These results suggest that VEGF expression and the induction of this protein are related to radiosensitivity and could be used to predict the effects of preoperative radiation therapy on oral squamous cell carcinoma. (author)

High percentage of oral lichen planus and lichenoid lesion in oral squamous cell carcinomas.

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Ruokonen, Hellevi M A; Juurikivi, Aino; Kauppila, Timo; Heikkinen, Anna Maria; Seppänen-Kaijansinkko, Riitta

2017-08-01

Oral lichen planus (OLP) and lichenoid lesions (OLL) are regarded as precursor lesions of oral squamous cell carcinoma (OSCC) with potential for malignant transformation. This potential is not clear due to difficulties in diagnosis of OLP and OLL. Our aim was therefore to evaluate previously identified OLP and OLL as precursor lesions in OSCC and to identify cancer related etiological factors such as smoking and alcohol consumption. We retrospectively reviewed all cases (total 323, comprising 164 females and 159 males) with OSCC treated at the Department of Oral and Maxillofacial Diseases and Surgery, Helsinki University Hospital during 2015. Confirmed by histopathological biopsy, 58 (17.9%) had OLP and 13 had OLL (4.0%) as precursor lesion. Patients with OLP were slightly older than those without it. OLP was more common in females than in males (p < .0001). TN class 1 tumors were more prevalent among patients with OLP or OLL (p = .006) and cancer relapses less common (p = .005). Smoking was less frequent in patients with OLP and OLL (p < .0001). Also alcohol abuse was less frequent among these patients (p < .001). Our findings confirm the importance of active follow-up of all patients with OLP and OLL even in patients who do not fit a traditional high-risk category for OSCC.

Association of differential β-catenin expression with Oct-4 and Nanog in oral squamous cell carcinoma and their correlation with clinicopathological factors and prognosis.

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Ravindran, Gokulan; Sawant, Sharada S; Hague, Angela; Kingsley, Karl; Devaraj, Halagowder

2015-07-01

The re-expression of pluripotent markers (Oct-4 and Nanog) and the reactivation of stem cell-related pathways in oral carcinoma have been well researched. However, the relationship between the stem cell signaling molecule β-catenin and pluripotent markers Oct-4 and Nanog in oral cancer is yet to be studied in detail. Therefore, we have investigated the correlation among Oct-4, Nanog, and β-catenin in oral squamous cell carcinoma, which, in turn, could provide valuable insight into its prognostic significance. The immunohistochemical analysis was performed for 60 cases of oral cancer to study the expression pattern of Oct-4, Nanog, and β-catenin. Whereas immunofluorescence analysis was used to investigate the co-localization of β-catenin with Oct-4 and Nanog in oral carcinoma tissues and H314 cell line. Finally, co-immunoprecipitation analysis was used to study the possible interaction between β-catenin and Oct-4 in oral carcinoma cells. β-catenin, Oct-4, and Nanog showed significant correlation with lymph node metastasis, stage, grade, and prognosis in oral squamous cell carcinoma. Interestingly, a significant positive correlation was found among the expression of Oct-4, Nanog, and β-catenin. Moreover, the interaction between β-catenin and Oct-4 was observed in oral cancer. The positive correlation among Oct-4, Nanog, and β-catenin suggests their coordinated role in maintaining proliferation in oral carcinoma cells. The interaction between β-catenin and Oct-4 may be a crucial event in oral carcinogenesis. On the other hand, β-catenin, Oct-4, and Nanog could be used as independent prognostic markers of oral squamous cell carcinoma. © 2014 Wiley Periodicals, Inc.

A histochemical comparison of methyl green-pyronin, and hematoxylin and eosin for detecting apoptotic cells in oral squamous cell carcinoma, oral leukoplakia, oral submucous fibrosis and normal oral mucosa.

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Sumedha, S; Kotrashetti, V S; Somannavar, P; Nayak, R; Babji, D

2015-05-01

Analysis of apoptotic cells in oral pathological states could be useful for determining the rates of tissue turnover, which would help determine prognosis. The use of histochemical stains such as hematoxylin and eosin (H & E) and methyl green-pyronin (MGP) can provide a simple and cost-effective method for detecting apoptotic cells. We compared the efficacy of MGP and H & E for detecting apoptotic cells in oral squamous cell carcinoma (OSCC), oral leukoplakia (OL), oral submucous fibrosis (OSMF) and normal oral mucosa (NOM). Ten cases each of OSCC, OSMF, OL and NOM were retrieved from the archives and two serial sections were stained, one with H & E and the other with MGP. Apoptotic cells were identified at 100 x magnification and the apoptotic index was calculated. Apoptotic cells were distinguished more readily in MGP stained sections than in those stained with H & E. Also, the apoptotic cell count was greater in OSCC compared to OL, OSMF and NOM. We concluded that MGP staining can be used as a routine, cost-effective method for detecting apoptotic cells.

Salivary analytes in patients with oral squamous cell carcinoma.

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Fuchs, Petra Nola; Rogić, Dunja; Vidović-Juras, Danica; Susić, Mato; Milenović, Aleksandar; Brailo, Vlaho; Boras, Vanja Vucićević

2011-06-01

Literature data indicates that measurement of certain salivary constituents might serve as a useful diagnostic/prognostic tool in the patients with oral squamous cell carcinoma (OSCC). In 24 patients with OSCC (60 +/- 2.5 yrs) and in 24 controls (24 +/- 3.7 yrs) we have determined levels of salivary magnesium, calcium, copper, chloride, phosphate, potassium, sodium, total proteins and amylase. Sodium, potassium and chloride were determined by indirect potentiometry whereas copper, magnesium and phosphate were determined by atomic absorption spectrophotometry. Total proteins were determined by pyrogalol colorimetric method. Amylase levels were determined by continued colorimetric method. Statistical analysis was performed by use of chi2 test and Spearman's correlation test. The results of this study indicate that the concentrations of sodium and chloride were significantly elevated in patients with OSCC when compared to the controls. However, level of total protein was significantly decreased when compared to the healthy controls. Furthermore, there was a negative correlation between alcohol consumption and total protein concentration in patients with oral carcinoma. We might conclude that in patients with OSCC increased salivary sodium and chloride might reflect their overall dehydration status due to alcohol consumption rather than consequence of OSCC itself.

Oral squamous cell carcinoma: clinicopathological features from 346 cases from a single Oral Pathology service during an 8-year period

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PIRES, Fábio Ramôa; RAMOS, Amanda Barreto; de OLIVEIRA, Jade Bittencourt Coutinho; TAVARES, Amanda Serra; da LUZ, Priscilla Silva Ribeiro; dos SANTOS, Teresa Cristina Ribeiro Bartholomeu

2013-01-01

Epidemiological data from oral squamous cell carcinoma (OSCC) is mostly derived from North American, European and East Asian populations. Objective The aim of this study was to report the demographic and clinicopathological features from OSCC diagnosed in an Oral Pathology service in southeastern Brazil in an 8-year period. Material and Methods All OSCC diagnosed from 2005 to 2012 were reviewed, including histological analysis of all hematoxylin and eosin stained slides and review of all demographic and clinical information from the laboratory records. Results A total of 346 OSCC was retrieved and males represented 67% of the sample. Mean age of the patients was 62.3 years-old and females were affected a decade older than males (pOral Pathology laboratory in southeastern Brazil and have highlighted several differences in clinicopathological features when comparing male and female OSCC-affected patients. PMID:24212993

Detection of survivin, carcinoembryonic antigen and ErbB2 level in oral squamous cell carcinoma patients.

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Li, Shu-Xia; Yang, Yan-Qi; Jin, Li-Jian; Cai, Zhi-Gang; Sun, Zheng

2016-01-01

The aim of this study was to detect the survivin, carcinoembryonic antigen (CEA) and ErbB2 in the saliva, serum and local tumor-exfoliated cells of oral squamous cell carcinoma (OSCC) patients, for providing reliable tumor markers for the early detection of oral malignant cancer. The saliva, serum, and local tumor-exfoliated cell samples of 26 OSCC patients without chemotherapy and 10 non-cancer patients were collected in Department of Oral and Maxillofacial Surgery, School of Stomatology, Peking University. The contents of survivin, CEA and ErbB2 using were detected usingenzyme-linked immunosorbent assay. The survivin and CEA levels in saliva and local tumor-exfoliated cells of OSCC patients were significantly higher than those in the non-cancer patients (P oral malignant cancer.

Revisiting the association between candidal infection and carcinoma, particularly oral squamous cell carcinoma

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Marina Mohd Bakri

2010-12-01

Full Text Available Background: Tobacco and alcohol are risk factors associated with cancer of the upper aerodigestive tract, but increasingly the role of infection and chronic inflammation is recognized as being significant in cancer development. Bacteria, particularly Helicobacter pylori, and viruses such as members of the human papilloma virus family and hepatitis B and C are strongly implicated as etiological factors in certain cancers. There is less evidence for an association between fungi and cancer, although it has been recognized for many years that white patches on the oral mucosa, which are infected with Candida, have a greater likelihood of undergoing malignant transformation than those that are not infected. Objective: This article reviews the association between the development of oral squamous cell carcinoma in potentially malignant oral lesions with chronic candidal infection and describes mechanisms that may be involved in Candida-associated malignant transformation.

Mast Cells: Key Players in the Shadow in Oral Inflammation and in Squamous Cell Carcinoma of the Oral Cavity

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Gaje, Pusa Nela; Amalia Ceausu, Raluca; Jitariu, Adriana; Popovici, Ramona Amina; Raica, Marius

2016-01-01

Although mast cells (MCs) have been discovered over 130 years ago, their function was almost exclusively linked to allergic affections. At the time being, it is well known that MCs possess a great variety of roles, in both physiologic and pathologic conditions. In the oral tissues, MCs release different proinflammatory cytokines, tumor necrosis factor alpha (TNF-α), that promote leukocyte infiltration in various inflammatory states of the oral cavity. These cells play a key role in the inflammatory process and, as a consequence, their number changes in different pathologic conditions of the oral cavity, like gingivitis, periodontitis, and so on. MCs also represent a rich source of proteases, especially of mast cell tryptase and chymase, which directly degrade the extracellular matrix through their proteolytic activity and thus indirectly stimulate angiogenesis and facilitate invasion and metastasis. It may be stated that mast cells could have an impact on primary tumor development, progression, and metastases in oral squamous cell carcinoma. By understanding the role of mast cells in the pathogenesis of different inflammatory and tumor diseases of the oral cavity, these cells may become therapeutic targets that could possibly improve the prognosis and survival of these patients. PMID:27847826

Tumor necrosis factor-α enhanced fusions between oral squamous cell carcinoma cells and endothelial cells via VCAM-1/VLA-4 pathway

International Nuclear Information System (INIS)

Song, Kai; Zhu, Fei; Zhang, Han-zhong; Shang, Zheng-jun

2012-01-01

Fusion between cancer cells and host cells, including endothelial cells, may strongly modulate the biological behavior of tumors. However, no one is sure about the driving factors and underlying mechanism involved in such fusion. We hypothesized in this study that inflammation, one of the main characteristics in tumor microenvironment, serves as a prominent catalyst for fusion events. Our results showed that oral cancer cells can fuse spontaneously with endothelial cells in co-culture and inflammatory cytokine tumor necrosis factor-α (TNF-α) increased fusion of human umbilical vein endothelium cells and oral cancer cells by up to 3-fold in vitro. Additionally, human oral squamous cell carcinoma cell lines and 35 out of 50 (70%) oral squamous carcinoma specimens express VLA-4, an integrin, previously implicated in fusions between human peripheral blood CD34-positive cells and murine cardiomyocytes. Expression of VCAM-1, a ligand for VLA-4, was evident on vascular endothelium of oral squamous cell carcinoma. Moreover, immunocytochemistry and flow cytometry analysis revealed that expression of VCAM-1 increased obviously in TNF-α-stimulated endothelial cells. Anti-VLA-4 or anti-VCAM-1 treatment can decrease significantly cancer–endothelial adhesion and block such fusion. Collectively, our results suggested that TNF-α could enhance cancer–endothelial cell adhesion and fusion through VCAM-1/VLA-4 pathway. This study provides insights into regulatory mechanism of cancer–endothelial cell fusion, and has important implications for the development of novel therapeutic strategies for prevention of metastasis. -- Highlights: ► Spontaneous oral cancer–endothelial cell fusion. ► TNF-α enhanced cell fusions. ► VCAM-1/VLA-4 expressed in oral cancer. ► TNF-α increased expression of VCAM-1 on endothelial cells. ► VCAM-1/VLA-4 mediated TNF-α-enhanced cell fusions.

Tumor necrosis factor-{alpha} enhanced fusions between oral squamous cell carcinoma cells and endothelial cells via VCAM-1/VLA-4 pathway

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Song, Kai; Zhu, Fei; Zhang, Han-zhong [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Shang, Zheng-jun, E-mail: shangzhengjun@hotmail.com [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); First Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan (China)

2012-08-15

Fusion between cancer cells and host cells, including endothelial cells, may strongly modulate the biological behavior of tumors. However, no one is sure about the driving factors and underlying mechanism involved in such fusion. We hypothesized in this study that inflammation, one of the main characteristics in tumor microenvironment, serves as a prominent catalyst for fusion events. Our results showed that oral cancer cells can fuse spontaneously with endothelial cells in co-culture and inflammatory cytokine tumor necrosis factor-{alpha} (TNF-{alpha}) increased fusion of human umbilical vein endothelium cells and oral cancer cells by up to 3-fold in vitro. Additionally, human oral squamous cell carcinoma cell lines and 35 out of 50 (70%) oral squamous carcinoma specimens express VLA-4, an integrin, previously implicated in fusions between human peripheral blood CD34-positive cells and murine cardiomyocytes. Expression of VCAM-1, a ligand for VLA-4, was evident on vascular endothelium of oral squamous cell carcinoma. Moreover, immunocytochemistry and flow cytometry analysis revealed that expression of VCAM-1 increased obviously in TNF-{alpha}-stimulated endothelial cells. Anti-VLA-4 or anti-VCAM-1 treatment can decrease significantly cancer-endothelial adhesion and block such fusion. Collectively, our results suggested that TNF-{alpha} could enhance cancer-endothelial cell adhesion and fusion through VCAM-1/VLA-4 pathway. This study provides insights into regulatory mechanism of cancer-endothelial cell fusion, and has important implications for the development of novel therapeutic strategies for prevention of metastasis. -- Highlights: Black-Right-Pointing-Pointer Spontaneous oral cancer-endothelial cell fusion. Black-Right-Pointing-Pointer TNF-{alpha} enhanced cell fusions. Black-Right-Pointing-Pointer VCAM-1/VLA-4 expressed in oral cancer. Black-Right-Pointing-Pointer TNF-{alpha} increased expression of VCAM-1 on endothelial cells. Black

Oral cavity squamous cell carcinoma: Role of pretreatment imaging and its influence on management

International Nuclear Information System (INIS)

Arya, S.; Rane, P.; Deshmukh, A.

2014-01-01

Squamous cell carcinoma (SCC) is the commonest malignancy in the oral cavity. The oral cavity has several subsites. Knowledge of the patterns of disease spread at each subsite with the impact on treatment and prognosis provides a deeper understanding of the role of imaging. Information from imaging helps accurate staging, assess resectability, and plan multimodality treatment. Mandibular erosion, posterior soft tissue extent, and perineural spread influence treatment and prognosis in gingival, buccal, and retromolar trigone (RMT) cancers. Multidetector computed tomography (MDCT) with multiplanar reformations and bone and soft tissue algorithms provides the highest specificity for bone erosion. Hard palate SCC is optimally imaged with contrast-enhanced magnetic resonance imaging (MRI) to detect perineural spread. In oral tongue and floor of the mouth (FOM) SCC, extrinsic muscle invasion, extension across the midline, extent of posterior and inferior spread, and proximity to the hyoid are issues that impact therapeutic options. Contrast-enhanced MRI is the optimal imaging method for staging the primary due to its superior soft tissue resolution. In oral tongue SCCs with tumour thickness ≤4 mm, elective neck dissection can be avoided. For nodal staging (N-staging), all imaging methods are comparable, but fall short of surgical staging. Sentinel lymph node biopsy has a promising role in N-staging. Positron emission tomography (PET)/integrated PET/CT has no role in evaluating the clinically negative neck. PET/CT has a role in pretreatment evaluation of advanced oral cavity SCC for depicting distant metastases and for mapping nodal extent in the clinically positive neck. Diffusion-weighted MRI, dynamic contrast-enhanced MRI, and CT perfusion have a potential role as baseline pretreatment studies for response assessment to chemoradiation in advanced oral cavity SCC. - Highlights: • Brief outline of treatment principles in oral cavity squamous cell carcinoma (OCSCC

A novel indole-3-carbinol derivative inhibits the growth of human oral squamous cell carcinoma in vitro.

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Weng, Jing-Ru; Bai, Li-Yuan; Omar, Hany A; Sargeant, Aaron M; Yeh, Ching-Tung; Chen, Yuan-Yin; Tsai, Ming-Hsui; Chiu, Chang-Fang

2010-10-01

Indole-3-carbinol (I3C), a naturally occurring phytochemical found in cruciferous vegetables, has received much attention due to its translational potential in cancer prevention and therapy. In this study, we investigated the antitumor effects of OSU-A9, a structurally optimized I3C derivative, in a panel of oral squamous cell carcinoma cell lines, SCC4, SCC15, and SCC2095. The antiproliferative effect of OSU-A9 was approximately two-orders-of-magnitude higher than that of I3C. Importantly, normal human oral keratinocytes were less sensitive to OSU-A9 than oral cancer cells. This antiproliferative effect of OSU-A9 was attributable to the induction of mitochondrial-dependent apoptosis as evidenced by sub-G1 accumulation of cells, poly ADP-ribose polymerase cleavage, and cytochrome c release from the mitochondria. OSU-A9 down regulates Akt and NF-κB signaling pathways, leading to changes in many downstream effectors involved in regulating cell cycle and apoptosis. Moreover, the observed down regulation of IKKα and IKKβ expression by OSU-A9 is not reported for I3C. OSU-A9 also induces both the production of reactive oxygen species and the endoplasmic reticulum stress. Taken together, these results suggest the translational value of OSU-A9 in oral squamous cell cancer therapy in the future. Copyright © 2010 Elsevier Ltd. All rights reserved.

Neoadjuvant radiochemotherapy and radical resection for advanced squamous cell carcinoma of the oral cavity. Outcome of 134 patients

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Eich, H.T.; Loeschcke, M.; Kocher, M.; Bongartz, R.; Mueller, R.P.; Scheer, M.; Zoeller, J.E.; Wacker, S.

2008-01-01

Background and purpose: several multimodal strategies have been developed to treat patients with squamous cell carcinoma of the oral cavity. The advantages of preoperative radiochemotherapy are downstaging of the primary tumor, an increased resectability rate, and the elimination of micrometastases. After successful phase II trials, the following therapy regimen for resectable advanced oral carcinoma was applied. Patients and methods: 134 patients with resectable squamous cell carcinoma of the oral cavity stage II-IV received neoadjuvant radiochemotherapy consisting of 39.6 Gy in daily fractions of 1.8 Gy and concomitant carboplatin (70 mg/m 2 days 1-5). Radical resection and neck dissection were carried out afterwards. Results: after a median follow-up of 73 months, 82 patients (61%) had died. 54 patients (40%) experienced locoregional relapses or distant metastases. The overall survival was 65% ± 4% after 2 years and 45% ± 4% after 5 years. Cox regression survival analysis identified tumor regression, extracapsular lymph node spread and resection state as prognostic factors. Side effects of grade 3-4 were rare. Conclusion: neoadjuvant radiochemotherapy with subsequent radical surgery can be recommended as an effective and safe treatment for primary resectable advanced tumors of the oral cavity. Acute and long-term toxicities appear to be moderate. (orig.)

TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas.

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Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Revathidevi, Sundaramoorthy; Arun, Kanagaraj; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Rajkumar, Kottayasamy Seenivasagam; Ajay, Chandrasekar; Rajaraman, Ramamurthy; Ramani, Rajendren; Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan

2016-06-01

Squamous cell carcinoma (SCC) of the uterine cervix and oral cavity are most common cancers in India. Telomerase reverse transcriptase (TERT) overexpression is one of the hallmarks for cancer, and activation through promoter mutation C228T and C250T has been reported in variety of tumors and often shown to be associated with aggressive tumors. In the present study, we analyzed these two hot spot mutations in 181 primary tumors of the uterine cervix and oral cavity by direct DNA sequencing and correlated with patient's clinicopathological characteristics. We found relatively high frequency of TERT hot spot mutations in both cervical [21.4 % (30/140)] and oral [31.7 % (13/41)] squamous cell carcinomas. In cervical cancer, TERT promoter mutations were more prevalent (25 %) in human papilloma virus (HPV)-negative cases compared to HPV-positive cases (20.6 %), and both TERT promoter mutation and HPV infection were more commonly observed in advanced stage tumors (77 %). Similarly, the poor and moderately differentiated tumors of the uterine cervix had both the TERT hot spot mutations and HPV (16 and 18) at higher frequency (95.7 %). Interestingly, we observed eight homozygous mutations (six 228TT and two 250TT) only in cervical tumors, and all of them were found to be positive for high-risk HPV. To the best of our knowledge, this is the first study from India reporting high prevalence of TERT promoter mutations in primary tumors of the uterine cervix and oral cavity. Our results suggest that TERT reactivation through promoter mutation either alone or in association with the HPV oncogenes (E6 and E7) could play an important role in the carcinogenesis of cervical and oral cancers.

[Comparative analysis of methylation profiles in tissues of oral leukoplakia and oral squamous cell carcinoma].

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Fu, J; Su, Y; Liu, Y; Zhang, X Y

2018-04-09

Objective: To compare the methylation profiles in tissues of oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC) with healthy tissues of oral mucosa, in order to identify the role of DNA methylation played in tumorigenesis. Methods: DNA samples extracted from tissues of 4 healthy oral mucosa, 4 OSCC and 4 OLK collected from patients of the Department of Oral Medicine, Capital Medical University School of Stomatology were examined and compared using Methylation 450 Bead Chip. The genes associated with differentially methylated CpG sites were selected for gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment. Results: Multiple differentially methylated CpG sites were identified by using the above mentioned assay. Hypermethylation constitutes 86.18% (23 290/27 025) of methylation changes in OLK and hypomethylation accounts for 13.82% (3 734/27 025) of methylation changes. Both hypermethylated and hypomethylated CpG sites were markedly increased in OSCC tissue compared with OLK tissue. The majority of differentially methylated CpG sites were located outside CpG islands, with approximately one-fourth in CpG shores flanking the islands, which were considered highly important for gene regulation and tumorigenesis. Pathway analysis revealed that differentially methylated CpG sites in both OLK and OSCC patients shared the same pathway enrichments, most of which were correlated with carcinogenesis and cancer progression (e.g., DNA repair, cell cycle, and apoptosis). Conclusions: In the present study, methylation-associated alterations affect almost all pathways in the cellular network in both OLK and OSCC. OLK and OSCC shared similar methylation changes whether in pathways or genes, indicating that epigenetically they might have the same molecular basis for disease progression.

TP53 mutation and human papilloma virus status of oral squamous cell carcinomas in young adult patients

NARCIS (Netherlands)

Braakhuis, B.J.M.; Rietbergen, M.M.; Buijze, M.; Snijders, P.J.F.; Bloemena, E.; Brakenhoff, R.H.; Leemans, C.R.

2014-01-01

Objective Little is known about the molecular carcinogenesis of oral squamous cell carcinoma (OSCC) in young adult patients. The aim of this study was to investigate the detailed TP53 mutation and human papilloma virus (HPV) status of OSCC in patients, younger than 45 years. Methods TP53 mutations

The prevalence of squamous cell carcinoma in different sites of oral cavity at our Rural Health Care Centre in Loni, Maharashtra – a retrospective 10-year study

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Dadhich, Anuj; Saluja, Harish; Bawane, Shilpa; Sachdeva, Shivani

2017-01-01

Aim of the study Oral cancer ranks in the top three of all cancers in India and is quickly becoming a global health priority. More than 90% of oral and oropharyngeal cancers are squamous cell carcinoma. The purpose of this study was to document its incidence depending upon the involvement of different sites of oral cavity, and its variation with age and gender. Material and methods Histopathologically proven oral squamous cell carcinoma cases were collected from the department of oral and maxillofacial surgery RDC, PIMS. The cases were systematically grouped under three headings: anatomical sub-site of oral cavity, age group, and gender, which were analysed to calculate the prevalence of oral cancer. The study was undertaken after obtaining approval from the institutional Ethical Committee board. Results Among the different sites of oral cavity, the highest incidence (31.47%) of oral squamous cell carcinoma was seen for buccal mucosa in our study. The most affected age group (39.50%) were patients above 50 years old, predominantly involving males. Conclusions The population in this study were mostly from remote areas, among which a high rate of occurrence of oral cancer was encountered because the people were of low socio-economic class, had a casual attitude towards their health, high rate of tobacco consumption, and limited health care facilities. This study provides valuable data of the prevalence of oral cancer among the rural population. PMID:28947890

The prevalence of squamous cell carcinoma in different sites of oral cavity at our Rural Health Care Centre in Loni, Maharashtra – a retrospective 10-year study

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Parul Tandon

2017-06-01

Full Text Available Aim of the study : Oral cancer ranks in the top three of all cancers in India and is quickly becoming a global health priority. More than 90% of oral and oropharyngeal cancers are squamous cell carcinoma. The purpose of this study was to document its incidence depending upon the involvement of different sites of oral cavity, and its variation with age and gender. Material and methods : Histopathologically proven oral squamous cell carcinoma cases were collected from the department of oral and maxillofacial surgery RDC, PIMS. The cases were systematically grouped under three headings: anatomical sub-site of oral cavity, age group, and gender, which were analysed to calculate the prevalence of oral cancer. The study was undertaken after obtaining approval from the institutional Ethical Committee board. Results : Among the different sites of oral cavity, the highest incidence (31.47% of oral squamous cell carcinoma was seen for buccal mucosa in our study. The most affected age group (39.50% were patients above 50 years old, predominantly involving males. Conclusions : The population in this study were mostly from remote areas, among which a high rate of occurrence of oral cancer was encountered because the people were of low socio-economic class, had a casual attitude towards their health, high rate of tobacco consumption, and limited health care facilities. This study provides valuable data of the prevalence of oral cancer among the rural population.

Anti-tumor activity of cabozantinib by FAK down-regulation in human oral squamous cell carcinoma

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Da-Lu Li

2016-03-01

Full Text Available Cabozantinib is a tyrosine kinase inhibitor involved in inhibition of cell proliferation and colony formation. We studied anti-cancer properties of cabozantinib in oral squamous cell carcinoma cells. The viability of BHY and HSC-3 cells decreased with increase in cabozantinib concentration and time. The proliferation of cell lines was affected by increasing concentration of cabozantinib from 0.3 to 1.2 μM after 48 hours of treatment. The expression of MET and phosphorylated MET was not affected by cabozantinib treatment. Cabozantinib-treated cells when compared to control, showed concentration-dependent increase in BHY and HSC-3 cells during G2/M phase and decrease in S phase with increase in cabozantinib concentration. Annexin-V/propidium iodide double staining showed that cells with annexin-V increased with the increase in cabozantinib concentration. The expression of apoptosis related proteins cleaved caspase-3 and cleaved-PARP were increased with increase in cabozantinib concentration. It was also found that suppression of FAK activation and expression was dose dependent. The results from this study revealed that cabozantinib can be useful in developing a drug for effective treatment of oral squamous cell carcinoma cells.

Essentials of oral cancer.

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Rivera, César

2015-01-01

Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators.

Downregulation of TGF-beta receptor types II and III in oral squamous cell carcinoma and oral carcinoma-associated fibroblasts

International Nuclear Information System (INIS)

Meng, Wenxia; Xia, Qingjie; Wu, Lanyan; Chen, Sixiu; He, Xin; Zhang, Lin; Gao, Qinghong; Zhou, Hongmei

2011-01-01

The purpose of this study was to assess the expression levels for TβRI, TβRII, and TβRIII in epithelial layers of oral premalignant lesions (oral leukoplakia, OLK) and oral squamous cell carcinoma (OSCC), as well as in oral carcinoma-associated fibroblasts (CAFs), with the final goal of exploring the roles of various types of TβRs in carcinogenesis of oral mucosa. Normal oral tissues, OLK, and OSCC were obtained from 138 previously untreated patients. Seven primary human oral CAF lines and six primary normal fibroblast (NF) lines were established successfully via cell culture. The three receptors were detected using immunohistochemical (IHC), quantitative RT-PCR, and Western blot approaches. IHC signals for TβRII and TβRIII in the epithelial layer decreased in tissue samples with increasing disease aggressiveness (P < 0.05); no expression differences were observed for TβRI, in OLK and OSCC (P > 0.05); and TβRII and TβRIII were significantly downregulated in CAFs compared with NFs, at the mRNA and protein levels (P < 0.05). Exogenous expression of TGF-β1 led to a remarkable decrease in the expression of TβRII and TβRIII in CAFs (P < 0.05). This study provides the first evidence that the loss of TβRII and TβRIII expression in oral epithelium and stroma is a common event in OSCC. The restoration of the expression of TβRII and TβRIII in oral cancerous tissues may represent a novel strategy for the treatment of oral carcinoma

Frequency of p53 Gene Mutation and Protein Expression in Oral Squamous Cell Carcinoma

International Nuclear Information System (INIS)

Ara, N.; Atique, M.; Ahmed, S.; Bukhari, S. G. A.

2014-01-01

Objective: To determine the frequency of p53 gene mutation and protein expression in Oral Squamous Cell Carcinoma (OSCC) and to establish correlation between the two. Study Design: Analytical study. Place and Duration of Study: Histopathology Department and Molecular Biology Laboratory, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from May 2010 to May 2011. Methodology: Thirty diagnosed cases of OSCC were selected by consecutive sampling. Seventeen were retrieved from the record files of the AFIP, and 13 fresh/frozen sections were selected from patients reporting to the Oral Surgery Department, Armed Forces Institute of Dentistry (AFID). Gene p53 mutation was analyzed in all the cases using PCRSSCP analysis. DNA was extracted from the formalin-fixed and paraffin-embedded tissue sections and fresh/frozen sections. DNA thus extracted was amplified by polymerase chain reaction. The amplified products were denatured and finally analyzed by gel electrophoresis. Gene mutation was detected as electrophoretic mobility shift. The immunohistochemical marker p53 was applied to the same 30 cases and overexpression of protein p53 was recorded. Results: Immunohistochemical expression of marker p53 was positive in 67% (95% Confidence Interval (CI) 48.7 - 80.9) of the cases. Mutations of the p53 gene were detected in 23% (95% CI 11.5 - 41.2) of the OSCC. No statistically significant correlation was found between p53 gene mutation and protein p53 expression (rs = - 0.057, p = 0.765). Conclusion: A substantial number of patients have p53 gene mutation (23%) and protein p53 expression (67%) in oral squamous cell carcinoma (OSCC). (author)

Oral cavity squamous cell carcinoma - characteristics and survival in aboriginal and non-aboriginal Western australians.

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Frydrych, A M; Slack-Smith, L M; Parsons, R; Threlfall, T

2014-01-01

Squamous cell carcinoma (SCC) is the most common type of malignancy affecting the oral cavity. While exposures to main risk factors for oral SCC such as smoking and alcohol use are higher amongst the Aboriginal people, little is known about oral cancer in this population. This study aimed to describe characteristics and survival of oral SCC in Aboriginal and non-Aboriginal Western Australians. All primary oral SCC cases reported to the Western Australian Cancer Registry (WACR) between 1990 and 1999 were analysed with respect to person characteristics including: date of birth, sex and indigenous status; and disease characteristics including: date of biopsy, disease stage and site as well as date of recurrence and date of death. Exclusion criteria included diagnosis not based on incisional or excisional biopsy, diagnosis other than oral SCC or a history of another malignant neoplasm. Aboriginal individuals were more likely to reside in rural areas. No statistically significant differences in oral SCC characteristics and survival were noted between Aboriginal and non-Aboriginal Western Australians. This study provides new information on person and disease characteristics of Aboriginal Western Australians diagnosed with oral SCC.

CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

International Nuclear Information System (INIS)

Oue, Erika; Lee, Ji-Won; Sakamoto, Kei; Iimura, Tadahiro; Aoki, Kazuhiro; Kayamori, Kou; Michi, Yasuyuki; Yamashiro, Masashi; Harada, Kiyoshi; Amagasa, Teruo; Yamaguchi, Akira

2012-01-01

Highlights: ► Oral cancer cells synthesize CXCL2. ► CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. ► CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. ► We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first report showing the role of CXCL2 in cancer-associated bone destruction.

CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

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Oue, Erika [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Lee, Ji-Won; Sakamoto, Kei [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Iimura, Tadahiro [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Aoki, Kazuhiro [Section of Pharmacology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Kayamori, Kou [Section of Diagnostic Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Department of Pathology, Ome Municipal General Hospital, Ome, Tokyo (Japan); Michi, Yasuyuki; Yamashiro, Masashi; Harada, Kiyoshi; Amagasa, Teruo [Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Yamaguchi, Akira, E-mail: akira.mpa@tmd.ac.jp [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan)

2012-08-03

Highlights: Black-Right-Pointing-Pointer Oral cancer cells synthesize CXCL2. Black-Right-Pointing-Pointer CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. Black-Right-Pointing-Pointer CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. Black-Right-Pointing-Pointer We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first

The drug efficacy and adverse reactions in a mouse model of oral squamous cell carcinoma treated with oxaliplatin at different time points during a day

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Yang K

2013-06-01

Full Text Available Kai Yang,1,2 Ningbo Zhao,1 Dan Zhao,1,2 Dan Chen,1 Yadong Li1 1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 2Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing, People’s Republic of China Background: Recent studies have shown that the growth and proliferation of cancer cells in vivo exhibit circadian rhythm, and the efficacy and adverse reactions of platinum-based anticancer drugs administered at different times of the day vary significantly on colon cancer. However, since the circadian rhythms of growth and proliferation of various cancer cells often differ, the question of whether the administration of platinum anticancer drugs at different times of the day exerts significantly different efficacy and adverse effects on oral cancers remains to be elucidated. This study has compared the efficacy and adverse effects of oxaliplatin (L-OHP administration at different times during a day on oral squamous cell carcinoma in mice and has analyzed cellular circadian rhythms. Methods: The mouse model for oral squamous cell carcinoma was established in 75 nude mice, housed in a 12 hour light/12 hour dark cycle environment. The mice were randomly divided into five groups; four experimental groups were intravenously injected with L-OHP at four time points within a 24-hour period (4, 10, 16, and 22 hours after lights on [HALO]. The control group was intravenously injected with the same volume of saline. Treatment efficacy and adverse reactions were compared on the seventh day after the injection, at 22 HALO. The existence of circadian rhythms was determined by cosine analysis. Results: Only injections of L-OHP at 16 and 22 HALO significantly prolonged animal survival time. The adverse reactions in mice injected with L-OHP at 16 and 22 HALO were significantly less than those observed in mice administered L-OHP at 4 and 10 HALO

MVP expression in the prediction of clinical outcome of locally advanced oral squamous cell carcinoma patients treated with radiotherapy.

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Henríquez-Hernández, Luis Alberto; Moreno, Mercedes; Rey, Agustín; Lloret, Marta; Lara, Pedro C

2012-08-29

To explore the role of Major Vault Protein (MVP) in oral cavity squamous cell carcinoma patients. 131 consecutive patients suffering from oral cavity squamous cell carcinoma were included in the study. In the whole series, the mean follow-up for survivors was 123.11 ± 40.36 months. Patients in tumour stages I and II were referred to surgery; patients in stage III-IV to postoperative radiotherapy (mean dose = 62.13 ± 7.74 Gy in 1.8-2 Gy/fraction). MVP expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. MVP expression was positive in 112 patients (85.5%) and no relation was found with clinic pathological variables. MVP overexpression (those tumours with moderate or strong expression of the protein) was related to insulin-like growth factor receptor-1 (IGF-1R) expression (P = 0.014). Tumour stage of the disease was the most important prognostic factor related to survival. Tumours overexpressing MVP and IGF-1R were strongly related to poor disease-free survival (P = 0.008, Exp(B) = 2.730, CI95% (1.302-5.724)) and cause-specific survival (P = 0.014, Exp(B) = 2.570, CI95% (1.215-5.437)) in patients achieving tumour stages III-IV, in multivariate analysis. MVP and IGF-1R expression were related in oral squamous cell carcinoma and conferred reduced long-term survival in patients suffering from advanced stages of the disease.

MVP expression in the prediction of clinical outcome of locally advanced oral squamous cell carcinoma patients treated with radiotherapy

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Henríquez-Hernández, Luis Alberto; Moreno, Mercedes; Rey, Agustín; Lloret, Marta; Lara, Pedro C

2012-01-01

To explore the role of Major Vault Protein (MVP) in oral cavity squamous cell carcinoma patients. 131 consecutive patients suffering from oral cavity squamous cell carcinoma were included in the study. In the whole series, the mean follow-up for survivors was 123.11 ± 40.36 months. Patients in tumour stages I and II were referred to surgery; patients in stage III-IV to postoperative radiotherapy (mean dose = 62.13 ± 7.74 Gy in 1.8–2 Gy/fraction). MVP expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. MVP expression was positive in 112 patients (85.5%) and no relation was found with clinic pathological variables. MVP overexpression (those tumours with moderate or strong expression of the protein) was related to insulin-like growth factor receptor-1 (IGF-1R) expression (P = 0.014). Tumour stage of the disease was the most important prognostic factor related to survival. Tumours overexpressing MVP and IGF-1R were strongly related to poor disease-free survival (P = 0.008, Exp(B) = 2.730, CI95% (1.302-5.724)) and cause-specific survival (P = 0.014, Exp(B) = 2.570, CI95% (1.215-5.437)) in patients achieving tumour stages III-IV, in multivariate analysis. MVP and IGF-1R expression were related in oral squamous cell carcinoma and conferred reduced long-term survival in patients suffering from advanced stages of the disease

Investigation of extracellular microRNAs in oral squamous cell carcinoma, rheumatoid arthritis and mesenchymal stem cell differentiation

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Yan, Yan

serve as biomarkers for human diseases and can also act as mediators in cell-cell communication. In cancer, the abnormal expression of miRNAs in plasma has been observed. However, there is no report on the association of plasma miRNA expression with oral squamous cell carcinoma (OSCC) recurrence after...

Histopathologic, stereologic, epidemiologic, and clinical parameters in the prognostic evaluation of squamous cell carcinoma of the oral cavity

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Bundgaard, T; Bentzen, S M; Wildt, J

1996-01-01

BACKGROUND: Prognostic indicators that could assist in a more precise selection of patients with oral cancer for differentiated therapy would be clinically valuable.METHODS: A consecutive series of 161 cases of intraoral squamous cell carcinoma (SCC) occurring during a 5-year period in a population...

Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

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2018-04-10

Squamous Cell Carcinoma of the Oropharynx; Squamous Cell Carcinoma of the Larynx; Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Hypopharynx; Squamous Cell Carcinoma of the Paranasal Sinus; Head and Neck Squamous Cell Carcinoma; Squamous Cell Cancer; Head and Neck Carcinoma

Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line

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Zhang, Ping; Zhang, Zhiyuan; Zhou, Xiaojian; Qiu, Weiliu; Chen, Fangan; Chen, Wantao

2006-01-01

Cisplatin is widely used for chemotherapy of head and neck squamous cell carcinoma. However, details of the molecular mechanism responsible for cisplatin resistance are still unclear. The aim of this study was to identify the expression of genes related to cisplatin resistance in oral squamous cell carcinoma cells. A cisplatin-resistant cell line, Tca/cisplatin, was established from a cisplatin-sensitive cell line, Tca8113, which was derived from moderately-differentiated tongue squamous cell carcinoma. Global gene expression in this resistant cell line and its sensitive parent cell line was analyzed using Affymetrix HG-U95Av2 microarrays. Candidate genes involved in DNA repair, the MAP pathway and cell cycle regulation were chosen to validate the microarray analysis results. Cell cycle distribution and apoptosis following cisplatin exposure were also investigated. Cisplatin resistance in Tca/cisplatin cells was stable for two years in cisplatin-free culture medium. The IC50 for cisplatin in Tca/cisplatin was 6.5-fold higher than that in Tca8113. Microarray analysis identified 38 genes that were up-regulated and 25 that were down-regulated in this cell line. Some were novel candidates, while others are involved in well-characterized mechanisms that could be relevant to cisplatin resistance, such as RECQL for DNA repair and MAP2K6 in the MAP pathway; all the genes were further validated by Real-time PCR. The cell cycle-regulated genes CCND1 and CCND3 were involved in cisplatin resistance; 24-hour exposure to 10 μM cisplatin induced a marked S phase block in Tca/cisplatin cells but not in Tca8113 cells. The Tca8113 cell line and its stable drug-resistant variant Tca/cisplatin provided a useful model for identifying candidate genes responsible for the mechanism of cisplatin resistance in oral squamous cell carcinoma. Our data provide a useful basis for screening candidate targets for early diagnosis and further intervention in cisplatin resistance

Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line

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Zhang Ping

2006-09-01

Full Text Available Abstract Background Cisplatin is widely used for chemotherapy of head and neck squamous cell carcinoma. However, details of the molecular mechanism responsible for cisplatin resistance are still unclear. The aim of this study was to identify the expression of genes related to cisplatin resistance in oral squamous cell carcinoma cells. Methods A cisplatin-resistant cell line, Tca/cisplatin, was established from a cisplatin-sensitive cell line, Tca8113, which was derived from moderately-differentiated tongue squamous cell carcinoma. Global gene expression in this resistant cell line and its sensitive parent cell line was analyzed using Affymetrix HG-U95Av2 microarrays. Candidate genes involved in DNA repair, the MAP pathway and cell cycle regulation were chosen to validate the microarray analysis results. Cell cycle distribution and apoptosis following cisplatin exposure were also investigated. Results Cisplatin resistance in Tca/cisplatin cells was stable for two years in cisplatin-free culture medium. The IC50 for cisplatin in Tca/cisplatin was 6.5-fold higher than that in Tca8113. Microarray analysis identified 38 genes that were up-regulated and 25 that were down-regulated in this cell line. Some were novel candidates, while others are involved in well-characterized mechanisms that could be relevant to cisplatin resistance, such as RECQL for DNA repair and MAP2K6 in the MAP pathway; all the genes were further validated by Real-time PCR. The cell cycle-regulated genes CCND1 and CCND3 were involved in cisplatin resistance; 24-hour exposure to 10 μM cisplatin induced a marked S phase block in Tca/cisplatin cells but not in Tca8113 cells. Conclusion The Tca8113 cell line and its stable drug-resistant variant Tca/cisplatin provided a useful model for identifying candidate genes responsible for the mechanism of cisplatin resistance in oral squamous cell carcinoma. Our data provide a useful basis for screening candidate targets for early diagnosis

Expression of ABCG2 and Bmi-1 in oral potentially malignant lesions and oral squamous cell carcinoma

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Dalley, Andrew J; Pitty, Luke P; Major, Aidan G; AbdulMajeed, Ahmad A; Farah, Camile S

2014-01-01

Early diagnosis is vital for effective treatment of oral squamous cell carcinoma (OSCC). The optimal time for clinical intervention is prior to malignancy when patients present with oral potentially malignant lesions such as leukoplakia or erythroplakia. Transformation rates for oral dysplasia vary greatly and more rigorous methods are needed to predict the malignant potential of oral lesions. We hypothesized that the expression of two putative stem cell markers, ABCG2 and Bmi-1, would correlate with disease severity for non diseased, potentially malignant and OSCC specimens and cell lines derived from an equivalent range of tissues. We compared immunoreactive protein and relative gene expression of ABCG2 and Bmi-1 in eight cell lines derived from source tissues ranging in disease severity from normal (OKF6-TERT2) through mild and moderate/severe dysplasia (DOK, POE-9n) to OSCC (PE/CA-PJ15, SCC04, SCC25, SCC09, SCC15). We also analyzed immunoreactive protein expression of ABCG2 and Bmi-1 in 189 tissue samples with the same range of disease severity. A trend between oral lesion severity to ABCG2 and Bmi-1 immunostain intensity was observed. Flow cytometry of oral cell lines confirmed this trend and gave good correlation with RT-PCR results for ABCG2 (r = 0.919, P = 0.001; Pearson) but not Bmi-1 (r = −0.311). The results provide evidence of increased density of ABCG2 and Bmi-1-positive populations in malignant and oral potentially malignant lesions and derived cell lines, but that intragroup variability within IHC, flow cytometry, and RT-PCR results compromise the diagnostic potential of these techniques for discriminating oral dysplasia from normal tissue or OSCC

Evaluation of radiotherapy and chemotherapy treatment in patients of oral squamous cell carcinoma

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Sannomiya, Eduardo Kazuo; Medici Filho, Edmundo; Moraes, Luiz Cesar de; Castilho, Julio Cezar de Melo; Furukawa, Souhei

2003-01-01

We evaluated the effectiveness of radiotherapy combined with chemotherapy in patients with oral squamous cell carcinoma. Therefore, 1042 cases where reviewed in School Dentistry - Osaka Univ. Seven hundred and fifteen were male and three hundred and twenty-seven were female. Ora cancer was affected more male than female patients, with mean age of 582 years old. The tongue was the most common anatomic localization of oral cancer. In tongue, the use of external radiotherapy y combined with brachytherapy and brachytherapy isolated presented better results than chemotherapy combined with external radiotherapy. In buccal mucosa, there was not differences in the treatment's results using external radiotherapy and combined chemotherapy and external radiotherapy. In tongue's floor and upper and jaw gingiva the combined treatment with chemotherapy and external radiotherapy presented better results than isolated external radiotherapy. (author)

MiR-21 expression in the tumor stroma of oral squamous cell carcinoma

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Hedbäck, Nora; Jensen, David H; Specht, Lena

2014-01-01

Oral squamous cell carcinoma (OSCC) patients have a high mortality rate; thus, new clinical biomarkers and therapeutic options are needed. MicroRNAs (miRNAs) are short noncoding RNAs that regulate posttranscriptional gene expression and are commonly deregulated in OSCC and other cancers. Micro......-stage) in a multivariate analysis. In summary, we have shown that miR-21 is located in the carcinoma cells, stroma and blood vessels of tumors, and its expression specifically in the stromal compartment has a negative prognostic value in OSCC....

Viral infection and oral habits as risk factors for oral squamous cell carcinoma in Yemen: a case-control study.

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Nasher, Akram T; Al-Hebshi, Nezar N; Al-Moayad, Ebtisam E; Suleiman, Ahmed M

2014-11-01

The role of qat chewing, tobacco (shammah) dipping, smoking, alcohol drinking, and oral viral infection as risk factors for oral squamous cell carcinoma (OSCC) in Yemen was assessed. A total of 60 cases of OSCC and 120 age- and gender-matched controls were analyzed with respect to demographic data, history of oral habits, and the presence of human papillomavirus (HPV)-16, HPV-18, or Epstein-Barr virus (EBV) as determined by Taqman quantitative polymerase chain reaction. Logistic regression analysis was used to identify independent predictors of the disease. Shammah use was the only risk factor for OSCC, with an odds ratio of 12.6 (CI, 3.3-48.2) and 39 (CI, 14-105) for the ex-users and current users, respectively. The association of shammah use alone with OSCC exceeded that of shammah use in combination with qat chewing, smoking, or both. EBV infection, smoking, and qat chewing showed no association with OSCC, while neither HPV-16 nor HPV-18 were detected in any sample. Shammah use is a major risk factor for oral cancer in Yemen. Copyright © 2014 Elsevier Inc. All rights reserved.

Aggressive Recurrence of Oral Squamous Cell Carcinoma in a patient with Fanconi’s Anaemia (FA)

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Nolan, M.

2017-03-01

Fanconi’s Anaemia is a rare autosomal recessive disease for which the incidence of head and neck cancer can be increased 700-fold1. We report a case of a 31-year old Caucasian male with FA who initially presented in July 2007 with oral squamous cell carcinoma for which he received radical surgery and radiotherapy. He was disease-free until August 2015 when he presented with an extremely aggressive recurrence.

Advances of Salivary Proteomics in Oral Squamous Cell Carcinoma (OSCC Detection: An Update

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Rabia Sannam Khan

2016-12-01

Full Text Available Oral cancer refers to malignancies that have higher morbidity and mortality rates due to the late stage diagnosis and no early detection of a reliable diagnostic marker, while oral squamous cell carcinoma (OSCC is amongst the world’s top ten most common cancers. Diagnosis of cancer requires highly sensitive and specific diagnostic tools which can support untraceable hidden sites of OSCC, yet to be unleashed, for which plenty of biomarkers are identified; the most recommended biomarker detection medium for OSCC includes biological fluids, such as blood and saliva. Saliva holds a promising future in the search for new clinical biomarkers that are easily accessible, less complex, accurate, and cost effective as well as being a non-invasive technique to follow, by analysing the malignant cells’ molecular pathology obtained from saliva through proteomic, genomic and transcriptomic approaches. However, protein biomarkers provide an immense potential for developing novel marker-based assays for oral cancer, hence this current review offers an overall focus on the discovery of a panel of candidates as salivary protein biomarkers, as well as the proteomic tools used for their identification and their significance in early oral cancer detection.

Matrix metalloproteinase-7 and matrix metalloproteinase-25 in oral tongue squamous cell carcinoma.

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Mäkinen, Laura K; Häyry, Valtteri; Hagström, Jaana; Sorsa, Timo; Passador-Santos, Fabricio; Keski-Säntti, Harri; Haukka, Jari; Mäkitie, Antti A; Haglund, Caj; Atula, Timo

2014-12-01

Predicting the clinical course of early-stage oral tongue squamous cell carcinoma (SCC) is challenging. As matrix metalloproteinases (MMPs) are enzymes associated with invasion, metastasis, and poor survival in many cancers, we examined MMP-7 and MMP-25 in oral tongue SCC. We used tissue microarray (TMA) technique and immunohistochemistry to study the expression of MMP-7 and MMP-25 in 73 patients with stage I to II oral tongue SCC and compared their immunoexpressions with clinical data. Immunohistochemistry revealed MMP-7 and MMP-25 expression in 90% (n = 63 of 70) and 90% (n = 64 of 71) of the tumors, respectively. MMP-7 protein expression was associated with presence of occult cervical metastases (odds ratio [OR], 3.67; p = .013), increased invasion depth (OR, 4.60; p = .005), and higher tumor grade (OR, 3.30; p = .007). MMP-7 expression was predictive for poor outcome (p = .021). Immunostaining of MMP-25 did not correlate with any clinical parameters. We conclude that MMP-7, but not MMP-25, expression may have prognostic significance in early-stage oral tongue SCC. © 2014 Wiley Periodicals, Inc.

Cervical level IIb metastases in squamous cell carcinoma of the oral cavity: a systematic review and meta-analysis

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Kou Y

2017-09-01

Full Text Available Yurong Kou,1,* Tengfei Zhao,2,* Shaohui Huang,2 Jie Liu,3 Weiyi Duan,2 Yunjing Wang,2 Zechen Wang,2 Delong Li,2 Chunliu Ning,2 Changfu Sun2 1Department of Oral Biology, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Centre of Science Experiment, China Medical University, Shenyang, Liaoning, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to clarify whether level IIb dissection should be performed or avoided in the treatment of oral squamous cell carcinoma by meta-analysis.Materials and methods: Articles that were published before June 2017 were searched electronically in four databases (Web of Science, PubMed, Ovid and China National Knowledge Infrastructure without any date or language restrictions by two independent reviewers. Abstracts and full-text papers which investigated the cervical metastases to level IIb from primary head and neck cancers and were deemed potentially relevant were screened. Data were analyzed using RevMan 5.3.Results: Four hundred and fifty-five abstracts and 129 full-text papers were screened, and 22 studies were included in the analysis. Among the 2001 patients included, 112 patients had level IIb metastases, the pooled frequency of which was 6% (95% confidence interval [CI]: 4.0–7.0. Among the 400 patients with tongue squamous cell carcinoma from 12 studies, 37 patients had level IIb metastases, the pooled incidence of which was 7% (95% CI: 5.0–10.0. Metastases to level IIb always went together with level IIa, and only three patients were found to have isolated level IIb metastases without involving the other levels.Conclusion: Due to the low frequency of level IIb nodal metastases in oral squamous cell carcinoma patients and rare occurrence of isolated

Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

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Dudás, József; Fullár, Alexandra; Romani, Angela; Pritz, Christian; Kovalszky, Ilona; Hans Schartinger, Volker; Mathias Sprinzl, Georg; Riechelmann, Herbert

2013-01-01

Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factor κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells

Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

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Dudás, József, E-mail: jozsef.dudas@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Fullár, Alexandra, E-mail: fullarsz@gmail.com [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest (Hungary); Romani, Angela, E-mail: angela.romani@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Pritz, Christian, E-mail: christian.pritz@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Kovalszky, Ilona, E-mail: koval@korb1.sote.hu [1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest (Hungary); Hans Schartinger, Volker, E-mail: volker.schartinger@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Mathias Sprinzl, Georg, E-mail: georg.sprinzl@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Riechelmann, Herbert, E-mail: herbert.riechelmann@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)

2013-04-01

Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factor κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells.

Investigating a case of possible field cancerization in oral squamous cell carcinoma by the use of next-generation sequencing

DEFF Research Database (Denmark)

Tabatabaeifar, Siavosh; Larsen, Martin J.; Larsen, Stine R.

2017-01-01

Objectives Local recurrence and the development of second primary tumors (SPT) are important factors that can influence the survival rate of oral squamous cell carcinoma (OSCC) patients. We investigate the concept of field cancerization which proposes that normal tissue adjacent to the primary...

Evaluation of Microvascularity by CD34 Expression in Esophagus and Oral Squamous Cell Carcinoma.

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Shahsavari, Fatemeh; Farhadi, Sareh; Sadri, Donia; Sedehi, Marzieh

2015-06-01

The present study was scheduled to evaluate microvascularity by CD34 expression in esophagus and oral squamous cell carcinoma. This study was scheduled using 40 paraffin blocked samples including 20 of oral SCC and 20 of esophagus ones and Immunohistochemical staining was conducted using CD34 monoclonal antibody. Exact fisher test was used to evaluate frequency of expression between two studied groups. There was significant correlation between age and tumor size with CD34 expression in oral SCC samples (p 0.05). Also, there was no significant correlation between age, sex, tumor size and tumor differentiation level (grading) with CD34 expression in esophagus SCC samples (p > 0.05). There was no significant difference of CD34 expression frequency in oral and esophagus SCC (p = 0/583). Finally, CD34 expression was reported 'high' for major cases of esophagus and oral SCCs. It seems, other angiogenetic or nonangiogenetic factors except CD34 may play more important role and explain the different clinical behavior of SCC at recent different locations. Other factors would be considered along with CD34 expression to interpret different clinical behavior of SCC at recent different locations.

Comparative evaluation of the frequency of myofibroblasts between oral and cutaneous squamous cell carcinomas

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Ali Dodani

2016-09-01

Full Text Available Introduction: Differentiation of fibroblasts to myofibroblasts is an initial and very important event in tumor genesis. Myofibroblasts produce proteinases that stimulate invasion in cancers. Due to the more malignant potential of oral squamous cell carcinoma (OSCC compared to cutaneous squamous cell carcinoma (CSCC , the aim of the present study was to compare myofibroblasts between OSCC and CSCC to understand whether myofibroblasts can help more malignant potential of OSCC compared to CSCC or not. Materials &Methods: This cross-sectional study included 40 cases of OSCC and CSCC and 20 cases of normal skin and normal oral mucosa. Then, 4-micron sections of paraffin-embedded tissue blocks of studied groups were stained immunohistochemically with α-SMA antibody. Mean percentage of myofibroblasts was calculated in invasive fronts of OSCCs with CSCCs and also in normal samples and staining intensity of cells for α-SMA marker and distribution pattern of myofibroblasts were determined. Results: The differences of average percentage of myofibroblasts in OSCC and CSCC compared to normal groups were significant (Pvalue=0.007and Pvalue=0.003 respectively, but when we compared OSCCs and CSCCs, the difference was not significant. Also, there were no significant differences between OSCC and CSCC with regard to staining intensity and pattern. Conclusion: Different biologic behavior of OSCC compared to CSCC doesn’t depend on myofibroblasts and other factors can be involved.

MVP expression in the prediction of clinical outcome of locally advanced oral squamous cell carcinoma patients treated with radiotherapy

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Henríquez-Hernández Luis

2012-08-01

Full Text Available Abstract Objective To explore the role of Major Vault Protein (MVP in oral cavity squamous cell carcinoma patients. Subjects and Methods 131 consecutive patients suffering from oral cavity squamous cell carcinoma were included in the study. In the whole series, the mean follow-up for survivors was 123.11 ± 40.36 months. Patients in tumour stages I and II were referred to surgery; patients in stage III-IV to postoperative radiotherapy (mean dose = 62.13 ± 7.74 Gy in 1.8–2 Gy/fraction. MVP expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. Results MVP expression was positive in 112 patients (85.5% and no relation was found with clinic pathological variables. MVP overexpression (those tumours with moderate or strong expression of the protein was related to insulin-like growth factor receptor-1 (IGF-1R expression (P = 0.014. Tumour stage of the disease was the most important prognostic factor related to survival. Tumours overexpressing MVP and IGF-1R were strongly related to poor disease-free survival (P = 0.008, Exp(B = 2.730, CI95% (1.302-5.724 and cause-specific survival (P = 0.014, Exp(B = 2.570, CI95% (1.215-5.437 in patients achieving tumour stages III-IV, in multivariate analysis. Conclusions MVP and IGF-1R expression were related in oral squamous cell carcinoma and conferred reduced long-term survival in patients suffering from advanced stages of the disease.

Relationship between the Expression of Matrix Metalloproteinase and Clinicopathologic Features in Oral Squamous Cell Carcinoma

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Amir Hossein Jafarian

2015-05-01

Full Text Available Introduction: Squamous cell carcinoma of the oral cavity is one of the most important and common types of head and neck malignancy, with an estimated rate of 4% among all human malignancies. The aim of this study was to determine the association between expression of matrix metalloproteinase 2 and 9 and the clinicopathological features of oral squamous cell carcinoma (OSCC.   Materials and Methods: One hundred existing samples of formalin-fixed paraffin embedded specimens of OSCC were evaluated by immunohistochemistry staining for matrix metalloproteinase 2 and 9 antibodies. Samples were divided into four groups: negative, 50%. Patient records were assessed for demographic characteristics such as age and gender, smoking and family history of OSCC as well as tumor features including location, differentiation, stage and lymph node involvement.   Results: In this study, 58 patients (58% were male and 42 (42% female. The mean age of patients was 60.38±14.07 years. The average number of lymph nodes involved was 8.9±3.8. Tumoral grade, tumoral stage, lymphatic metastasis and history of smoking were significantly related to MMP2 and MMP9 expression.   Conclusion:  Our study demonstrated that MMP2 and MMP9 expression are important in the development of OSCC.

THE EXON 5, 6, 7, 8 OF P53 MUTATIONS IN ORAL SQUAMOUS CELLS CARCINOMA

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Retno P Rahayu

2012-04-01

Full Text Available Genetic instability may underlie the etiology of multistep carcinogenesis. The altered p53 gene observed in tumors may represent the expression of such instability and may allow the accumulation of other gene alterations caused by multiple mechanism. p53 gene is the guardian of the genome, that is why we pay more attention to this gene. In this study, we evaluated the significance of p53 mutation in 55 patient with oral squamous carcinoma. Thirty among them underwent well-differentiated carcinoma, while the remaining 25 patients underwent poorly differentiated carcinoma. The mutations were detected by PCR-SSCP (Single strand Conformational Polymorphism analysis in the region between exon 5 and exon 8. The results indicated that the p53 mutation in exon 5 (40%, exon 6 (28%, exon 7 (24% and exon 8 (8% were associated with poorly differentiated carcinoma, whereas mutation in exon 5 (10%, exon 6 (30%, exon 7 (40% and exon 8 (20% were associated with well-differentiated carcinoma. These observations suggest that p53 mutation in exon 5, 6, and 7 have strong correlation with poorly differentiated in oral squamous carcinoma while well-differentiated level was related with mutation in exon 6,7 and 8.

Impact of HPV infection on oral squamous cell carcinoma.

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Götz, Carolin; Drecoll, Enken; Straub, Melanie; Bissinger, Oliver; Wolff, Klaus-Dietrich; Kolk, Andreas

2016-11-22

Head and neck squamous cell carcinomas (HNSCC) are often divided by their aetiology. Noxae associated collectives are compared with the human papilloma virus (HPV)-associated group, whereas different localisations of oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas are mostly discussed as one single group. Our aim was to show that classification by aetiology is not appropriate for OSCC. HPV DNA was detected by PCR in 7 (3.47%) patients, and we identified 12 (5.94%) positive (+) cases by p16INK4a immunostaining. Only 4 (1.98%) of the p16INK4a+ cases were + for HPV using PCR. Our homogenous collective of OSCC allowed us to compare HPV+ and HPV negative (-) patients without creating bias for tumour localisation, age, gender or tumour stage. After testing OSCC samples for HPV positivity, we compared the results of two commonly used HPV detection methods, p16INK4a immunostaining and HPV DNA-related PCR, on 202 OSCC patients. HPV subtypes were determined with an HPV LCD Array Kit. Clinicopathological features of the patients were analysed, and the disease specific survival rates (DSS) for HPV+ and HPV- patients were obtained. p16INK4a immunostaining is a not a reliable HPV detection method for OSCC. Positive p16INK4a immunostaining did not agree with + results from PCR of HPV DNA. Furthermore, the influence of HPV-related oncogenic transformation in OSCC is overestimated. The significance of HPV infection remains clinically unclear, and its influence on survival rates is not relevant to OSCC cases.

Protease-activated receptor 2 modulates proliferation and invasion of oral squamous cell carcinoma cells.

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Al-Eryani, Kamal; Cheng, Jun; Abé, Tatsuya; Maruyama, Satoshi; Yamazaki, Manabu; Babkair, Hamzah; Essa, Ahmed; Saku, Takashi

2015-07-01

Based on our previous finding that protease-activated receptor 2 (PAR-2) regulates hemophagocytosis of oral squamous cell carcinoma (SCC) cells, which induces their heme oxygenase 1-dependent keratinization, we have formulated a hypothesis that PAR-2 functions in wider activities of SCC cells. To confirm this hypothesis, we investigated immunohistochemical profiles of PAR-2 in oral SCC tissues and its functional roles in cell proliferation and invasion in SCC cells in culture. The PAR-2 expression modes were determined in 48 surgical tissue specimens of oral SCC. Using oral SCC-derived cell systems, we determined both gene and protein expression levels of PAR-2. SCC cell proliferation and invasive properties were also examined in conditions in which PAR-2 was activated by the synthetic peptide SLIGRL. PAR-2 was immunolocalized in oral SCC and carcinoma in situ cells, especially in those on the periphery of carcinoma cell foci (100% of cases), but not in normal oral epithelia. Its expression at both gene and protein levels was confirmed in 3 oral SCC cell lines including ZK-1. Activation of PAR-2 induced ZK-1 cell proliferation in a dose-dependent manner. PAR-2-activated ZK-1 cells invaded faster than nonactivated ones. The expression of PAR-2 is specific to oral malignancies, and PAR-2 regulates the growth and invasion of oral SCC cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Anti-tumor effect of cisplatin in human oral squamous cell carcinoma was enhanced by andrographolide via upregulation of phospho-p53 in vitro and in vivo.

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Chen, Songjie; Hu, Hui; Miao, Shushu; Zheng, Jiayong; Xie, Zhijian; Zhao, Hui

2017-05-01

Oral squamous cell carcinoma is one of the most common neoplasm in the world. Despite the improvements in diagnosis and treatment, the outcome is still poor now. Thus, the development of novel therapeuticapproaches is needed. The aim of this study is to assess the synergistic anti-tumor effect of andrographolide with cisplatin (DDP) in oral squamous cell carcinoma CAL-27 cells in vitro and in vivo. We performed Cell Counting Kit-8 proliferation assay, apoptosis assay, and western blotting on CAL-27 cells treated with andrographolide, DDP or the combination in vitro. In vivo, we also treated CAL-27 xenografts with andrographolide or the combination, and performed terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and immunohistochemical analysis of Ki-67. The results showed the combination of andrographolide and DDP synergistically inhibited CAL-27 cell proliferation in vitro and caused tumor regression in vivo in the CAL-27 xenografts. In addition, the synergistic anti-tumor effect of andrographolide with synergistic was due to an enhanced apoptosis. Moreover, the combination therapy upregulated the expression level of p-p53 in vitro and decreased Ki-67 expression in vivo. Our data indicate that the combination treatment of andrographolide and DDP results in synergistic anti-tumor growth activity against oral squamous cell carcinoma CAL-27 in vitro and in vivo. These results demonstrated that combination of andrographolide with DDP was likely to represent a potential therapeutic strategy for oral squamous cell carcinoma.

MicroRNA alterations and associated aberrant DNA methylation patterns across multiple sample types in oral squamous cell carcinoma

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Wiklund, Erik Digman; Gao, Shan; Hulf, Toby

2011-01-01

MicroRNA (miRNA) expression is broadly altered in cancer, but few studies have investigated miRNA deregulation in oral squamous cell carcinoma (OSCC). Epigenetic mechanisms are involved in the regulation of >30 miRNA genes in a range of tissues, and we aimed to investigate this further in OSCC....

Anticancer Effects of Salvia miltiorrhiza Alcohol Extract on Oral Squamous Carcinoma Cells

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Wen-Hung Wang

2017-01-01

Full Text Available Researchers have reported significant effects from Danshen (Salvia miltiorrhiza in terms of inhibiting tumor cell proliferation and promoting apoptosis in breast cancer, hepatocellular carcinomas, promyelocytic leukemia, and clear cell ovary carcinomas. Here we report our data indicating that Danshen extracts, especially alcohol extract, significantly inhibited the proliferation of the human oral squamous carcinoma (OSCC cell lines HSC-3 and OC-2. We also observed that Danshen alcohol extract activated the caspase-3 apoptosis executor by impeding members of the inhibitor of apoptosis (IAP family, but not by regulating the Bcl-2-triggered mitochondrial pathway in OSCC cells. Our data also indicate that the extract exerted promising effects in vivo, with HSC-3 tumor xenograft growth being suppressed by 40% and 69% following treatment with Danshen alcohol extract at 50 and 100 mg/kg, respectively, for 34 days. Combined, our results indicate appreciable anticancer activity and significant potential for Danshen alcohol extract as a natural antioxidant and herbal human oral cancer chemopreventive drug.

Association of cancer metabolism-related proteins with oral carcinogenesis – indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?

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2014-01-01

Background Tumor metabolism is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Methods Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB, ATP synthase) were analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry and real-time polymerase chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins were correlated with proliferation activity (Ki-67) and apoptotic properties (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western blotting in cancer cell lines. Results Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic active regions of OSCC were strongly correlated with proliferating cancer (Ki-67+) cells without detection of apoptosis (TUNEL assay). Conclusions This study provides the first evidence of the expression of IGF-R1, glycolysis-related proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both, hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation characteristics are associated with the carcinogenesis of OSCC. Acidosis and OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP). Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial therapies (ROS generation) by natural compounds or synthetic vitamin derivatives may act as sensitizer for apoptosis in cancer cells mediated by adjuvant therapies in OSCC. PMID:25048361

Suprabasal expression of Ki-67 as a marker for the severity of oral epithelial dysplasia and oral squamous cell carcinoma

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Nidhi Dwivedi

2013-01-01

Full Text Available Background: Transition of the normal oral epithelium to dysplasia and to malignancy is featured by increased cell proliferation. To evaluate the hypothesis of distributional disturbances in proliferating and stem cells in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC. Aim: To evaluate layer wise expression of Ki-67 in oral epithelial dysplasia and in OSCC. Materials and Methods: Thirty histologically confirmed cases of oral epithelial dysplasia, fifteen cases of OSCC and five cases of normal buccal mucosa were immunohistochemically examined and nuclear expression of Ki-67 was counted according to basal, parabasal, and suprabasal layers in epithelial dysplasia and number of positive cells per 100 cells in OSCC as labeling index (LI. Results: Suprabasal expression of Ki-67 increased according to the severity of epithelial dysplasia and the difference was statistically significant ( P < 0.001. The mean Ki-67LI was 12.78 for low risk lesions, 28.68 for high risk lesions, 39.45 for OSCC and 13.6 for normal buccal mucosa. Conclusion: The results of the present study demonstrate the use of proliferative marker Ki-67 in assessing the severity of epithelial dysplasia. Suprabasal expression of Ki-67 provides an objective criteria for determining the severity of epithelial dysplasia and histological grading of OSCC.

Gender specific quality of life in patients with oral squamous cell carcinomas

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Maciejewski Oliver

2010-08-01

Full Text Available Abstract Background The goal of this study was to evaluate the somatic and psychological effects by means of QUALITY OF LIFE (QOL of surgical treatment of patients with oral squamous cell carcinoma. The factors gender, age, nicotine consumption, and tumour stage were taken into consideration. Methods 54 patients after surgical resection of oral squamous cell carcinomas (OSCC were analysed from 01.09.2005 to 31.05.2008. Inclusion criteria for the study were: age at least 18 years, no indication or treatment of synchronous and metachronous tumours. German translations of the EORTC H&N-35 and EORTC QLQ-C-30 questionnaires, as well as a general socioeconomic patient history were used as measuring instruments. The questionnaires were completed independently by the patients. The answers were translated into scale values for statistical evaluation using appropriate algorithms. Results Analysis of the EORTC-QLQ-C-30 questionnaires demonstrated a tendency of more negative assessment of emotional function among the female participants, and a more negative evaluation of social function among the male participants. Greater tumour sizes showed significantly lower bodily function (p = 0.018. While a smaller tumour size was significantly associated with lower cognitive functioning (p = 0.031. Other cofactors such as age, nicotine consumption, and tumour stage only showed a tendency to influence the quality of sleep and daily life. Conclusions The data obtained within this investigation demonstrated that gender had the most significant power on the subjectively perceived postoperative quality of life. This factor is important e.g. in preoperative decision making regarding immediate microvascular reconstruction after e.g. mandibular resection and therefore QOL assessment should become integral component of the care of patients with OSCC.

Prevalence of human papillomavirus infection in oral squamous cell carcinoma: a case-control study in Wuhan, China.

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Gan, Li-Li; Zhang, Hao; Guo, Ji-Hua; Fan, Ming-Wen

2014-01-01

High risk forms of the human papilloma virus (HPV) are generally accepted as necessary causative agents for cervical cancer. Recently, a possible relation between HPV and oral squamous cell carcinoma (OSCC) has also been noticed. The present study was conducted to investigate the prevalence of HPV infection in OSCCs in Wuhan city. DNA samples were collected from fresh tissues in 200 patients with OSCC and 68 normal controls. The polymerase chain reaction and direct sequencing were used to identify the HPV types in the samples. The prevalence of HPV of all types in the OSCC group was higher than in the control group (55/200 vs 2/68, OR=11.5, 95% CI=2.6-50.2). HPV16 and HPV18 were the main types detected, with HPV6 was the only low-risk type identified. High-risk HPV types HPV16 and HPV18 are prevalent in OSCC patients and may participate in the development of OSCC with traditional risk factors, tobacco and alcohol, possibly exerting synergistic effects. The results of multinomial logistic regression showed that those who smoked, consumed alcohol and with HPV infection have the highest risk of developing oral cancer (OR=13.3, 95% CI=3.1-56.8). Adjusted for age, smoking and alcohol use, HPV infection was independently associated with oral squamous cell carcinoma.

A loss of profilin-1 in late-stage oral squamous cell carcinoma.

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Adami, Guy R; O'Callaghan, Thomas N; Kolokythas, Antonia; Cabay, Robert J; Zhou, Yalu; Schwartz, Joel L

2017-08-01

The genes for PFN1 and TMSB4 are both highly expressed in oral tissue and both encode actin monomer binding proteins thought to play a role in cell motility and possibly other crucial parts of tumor progression. Oral brush cytology of epithelium from oral squamous cell carcinoma (OSCC) was used to measure PFN1 and TMSB4 mRNA in OSCC, while immunohistochemical analysis of tissue was used to check protein levels. High but variable expression of mRNAs encoding these two proteins was observed suggesting they may contribute to tumor characteristics in a subset of OSCCs. Both proteins were highly expressed in normal appearing basal epithelium, in the cytoplasm, and perinuclear area, while expression was minimal in upper epithelial layers. In OSCCs, expression of these proteins varied. In tumors classified as later stage, based on size and/or lymph node involvement, PFN1 levels were lower in tumor epithelium. A control gene, KRT13, showed expression in normal differentiated basal and suprabasal oral mucosa epithelial cells and as reported was lost in OSCC cells. Loss of PFN1 in tumor cells has been associated with lymph node invasion and metastasis in other tumor types, strengthening the argument that the protein has the potential to be a tumor suppressor in late-stage OSCC. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas.

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Rector, Jeff; Kapil, Sasha; Treude, Kelly J; Kumm, Phyllis; Glanzer, Jason G; Byrne, Brendan M; Liu, Shengqin; Smith, Lynette M; DiMaio, Dominick J; Giannini, Peter; Smith, Russell B; Oakley, Greg G

2017-02-07

Oral cancers are easily accessible compared to many other cancers. Nevertheless, oral cancer is often diagnosed late, resulting in a poor prognosis. Most oral cancers are squamous cell carcinomas that predominantly develop from cell hyperplasias and dysplasias. DNA damage is induced in these tissues directly or indirectly in response to oncogene-induced deregulation of cellular proliferation. Consequently, a DNA Damage response (DDR) and a cell cycle checkpoint is activated. As dysplasia transitions to cancer, proteins involved in DNA damage and checkpoint signaling are mutated or silenced decreasing cell death while increasing genomic instability and allowing continued tumor progression. Hyperphosphorylation of Replication Protein A (RPA), including phosphorylation of Ser4 and Ser8 of RPA2, is a well-known indicator of DNA damage and checkpoint activation. In this study, we utilize S4S8-RPA phosphorylation as a marker for cancer development and progression in oral squamous cell carcinomas (OSCC). S4S8-RPA phosphorylation was observed to be low in normal cells, high in dysplasias, moderate in early grade tumors, and low in late stage tumors, essentially supporting the model of the DDR as an early barrier to tumorigenesis in certain types of cancers. In contrast, overall RPA expression was not correlative to DDR activation or tumor progression. Utilizing S4S8-RPA phosphorylation to indicate competent DDR activation in the future may have clinical significance in OSCC treatment decisions, by predicting the susceptibility of cancer cells to first-line platinum-based therapies for locally advanced, metastatic and recurrent OSCC.

Raman spectroscopic study of keratin 8 knockdown oral squamous cell carcinoma derived cells

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Singh, S. P.; Alam, Hunain; Dmello, Crismita; Vaidya, Milind M.; Krishna, C. Murali

2012-03-01

Keratins are one of most widely used markers for oral cancers. Keratin 8 and 18 are expressed in simple epithelia and perform both mechanical and regulatory functions. Their expression are not seen in normal oral tissues but are often expressed in oral squamous cell carcinoma. Aberrant expression of keratins 8 and 18 is most common change in human oral cancer. Optical-spectroscopic methods are sensitive to biochemical changes and being projected as novel diagnostic tools for cancer diagnosis. Aim of this study was to evaluate potentials of Raman spectroscopy in detecting minor changes associated with differential level of keratin expression in tongue-cancer-derived AW13516 cells. Knockdown clones for K8 were generated and synchronized by growing under serum-free conditions. Cell pellets of three independent experiments in duplicate were used for recording Raman spectra with fiberoptic-probe coupled HE-785 Raman-instrument. A total of 123 and 96 spectra from knockdown clones and vector controls respectively in 1200-1800 cm-1 region were successfully utilized for classification using LDA. Two separate clusters with classification-efficiency of ~95% were obtained. Leave-one-out cross-validation yielded ~63% efficiency. Findings of the study demonstrate the potentials of Raman spectroscopy in detecting even subtle changes such as variations in keratin expression levels. Future studies towards identifying Raman signals from keratin in oral cells can help in precise cancer diagnosis.

Candida albicans infection in patients with oral squamous cell carcinoma

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Čanković Miloš

2010-01-01

Full Text Available Bacground/Aim. Systemic candidiasis in intensive care units remains an improtant problem due to antifungal resistance. Patients undergoing radiotherapy for head and neck cancer are at increased risk of developing oral candidiasis and they more frequent have prior fungi colonization. Due to identification of specific risk factors predisposing to fungal infection in order to threat such patients the aim of this study was to determine the presence of Candida species in patients with oral squamous cell carcinoma and compare it to the control subjects (patients with benign oral mucosal lesions. Methods. A total number of 30 consecutive oral cancer examined patients were included in this prospective study (24 men and 6 women with a mean age of 61.47 years, range 41-81 years. The control group consisted of 30 consecutive patients with histologically proven benign oral mucosal lesions (16 men and 14 women with a mean age of 54.53 years, range 16- 83 years. The samples for mycological examination were obtained by using sterile cotton swabs from the cancer lesion surface and in the patients of the control group from the benign mucosal lesion surface. Samples were inoculated in Sabouraud' dextrose agar. For identification purposes, Mackenzie germ tube test was performend on all isolates. Results. The prevalence of Candida was significantly higher in oral cancer patients than in control subjects (χ2 = 5.455, p = 0.020. Candida was found on nine of the 30 cancer surfaces; 5 (16.7% were identified as non-albicans Candida and 4 (13.3% as Candida albicans. In the control group, only Candida albicans was isolated from 2 (6.7% patients. In this study, no statistically significant differences in the presence of Candida species was found with respect to gender, age, smoking, alcohol consumption, wearing of dental protheses and the site of cancer lesion. Conclusion. The increased prevalence of yeasts on the surfaces of oral carcinoma indicates a need for their

Basaloid Squamous Cell Carcinoma Involving the Alveolar Ridge, Buccal & Lingual Vestibule - A Case Report

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Supriya Koshti

2013-01-01

Full Text Available Background: Basaloid squamous cell carcinoma of oral mucosa is a rare and aggressive variant of squamous cell carcinoma. They can be differentiated from squamous cell carcinomas by their distinct clinical and histopathological features. Methods: 45 year old female patient presented with extra oral exophytic mass and intra-oral ulcerative lesion on right buccal mucosa and vestibule. The patient was referred for routine blood examination and radiography followed by incisional biopsy. The biopsy specimen was fixed, processed and stained with Hematoxylin and Eosin for further microscopic examination. Results: On microscopic examination basaloid cells were seen proliferating along with dysplastic squamous cells in the connective tissue stroma. Conclusion: Based on the histopathological findings a diagnosis of ′Basaloid squamous cell carcinoma′ was made. The patient was referred to department of Oral and Maxillofacial Surgery for excision of the lesion followed by radiotherapy.

Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma

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van Kempen, Pauline M W; Noorlag, Rob; Braunius, Weibel W; Moelans, Cathy B; Rifi, Widad; Savola, Suvi; Koole, Ronald; Grolman, Wilko; van Es, Robert J J; Willems, Stefan M

2015-01-01

Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer treatment. We examined copy number status in 36 common oncogenes and tumor suppressor genes in a cohort of 191 oropharyngeal squamous cell carcinomas (OPSCC) and 164 oral cavity squamous cell carcinomas (OSCC) using multiplex ligation probe amplification. Copy number status was correlated with human papillomavirus (HPV) status in OPSCC, with occult lymph node status in OSCC and with patient survival. The 11q13 region showed gain or amplifications in 59% of HPV-negative OPSCC, whereas this amplification was almost absent in HPV-positive OPSCC. Additionally, in clinically lymph node-negative OSCC (Stage I–II), gain of the 11q13 region was significantly correlated with occult lymph node metastases with a negative predictive value of 81%. Multivariate survival analysis revealed a significantly decreased disease-free survival in both HPV-negative and HPV-positive OPSCC with a gain of Wnt-induced secreted protein-1. Gain of CCND1 showed to be an independent predictor for worse survival in OSCC. These results show that copy number aberrations, mainly of the 11q13 region, may be important predictors and prognosticators which allow for stratifying patients for personalized treatment of HNSCC. PMID:26194878

Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma

International Nuclear Information System (INIS)

Kempen, Pauline M W van; Noorlag, Rob; Braunius, Weibel W; Moelans, Cathy B; Rifi, Widad; Savola, Suvi; Koole, Ronald; Grolman, Wilko; Es, Robert J J van; Willems, Stefan M

2015-01-01

Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer treatment. We examined copy number status in 36 common oncogenes and tumor suppressor genes in a cohort of 191 oropharyngeal squamous cell carcinomas (OPSCC) and 164 oral cavity squamous cell carcinomas (OSCC) using multiplex ligation probe amplification. Copy number status was correlated with human papillomavirus (HPV) status in OPSCC, with occult lymph node status in OSCC and with patient survival. The 11q13 region showed gain or amplifications in 59% of HPV-negative OPSCC, whereas this amplification was almost absent in HPV-positive OPSCC. Additionally, in clinically lymph node-negative OSCC (Stage I–II), gain of the 11q13 region was significantly correlated with occult lymph node metastases with a negative predictive value of 81%. Multivariate survival analysis revealed a significantly decreased disease-free survival in both HPV-negative and HPV-positive OPSCC with a gain of Wnt-induced secreted protein-1. Gain of CCND1 showed to be an independent predictor for worse survival in OSCC. These results show that copy number aberrations, mainly of the 11q13 region, may be important predictors and prognosticators which allow for stratifying patients for personalized treatment of HNSCC

Differences in survival outcome between oropharyngeal and oral cavity squamous cell carcinoma in relation to HPV status.

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Lai, Kenneth; Killingsworth, Murray; Matthews, Slade; Caixeiro, Nicole; Evangelista, Carlyn; Wu, Xiao; Wykes, James; Samakeh, Alan; Forstner, Dion; Niles, Navin; Hong, Angela; Lee, Cheok Soon

2017-09-01

This study examined the prognostic significance of human papillomavirus (HPV) in patients with oropharyngeal and oral cavity squamous cell carcinoma (SCC). Tissue microarrays were constructed from oropharyngeal and oral cavity SCC (n = 143). The presence of functional HPV in tumour was determined by combined assessments of p16 immunohistochemistry and HPV in situ hybridisation. Oropharyngeal SCC patients presented with more advanced disease in comparison with oral cavity SCC patients (P = 0.001). HPV is present in 60% and 61% of oropharyngeal and oral cavity SCC patients, respectively. HPV-positive oropharyngeal SCC patients with advanced TNM stages displayed better overall and disease-free survival outcomes than HPV-negative patients (P = 0.022 and 0.046, respectively). Such survival differences were not observed in oral cavity SCC. HPV is common in both oropharyngeal and oral cavity SCC and is associated with better survival outcome in oropharyngeal SCC but not in oral cavity SCC patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Loss of heterozygosity at 9q33 and hypermethylation of the DBCCR1 gene in oral squamous cell carcinoma

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Gao, S.; Worm, J.; Guldberg, P.

2004-01-01

The DBCCR1 gene at chromosome 9q33 has been identified as a candidate tumour suppressor, which is frequently targeted by promoter hypermethylation in bladder cancer. Here, we studied the possible involvement of DBCCR1 in the development of oral squamous cell carcinoma. DNA from 34 tumours...

Gingival squamous cell carcinoma: A diagnostic impediment

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Rekha Rani Koduganti

2012-01-01

Full Text Available Oral squamous cell carcinomas represent 3% of cancers in men and 2% of cancers in women. More than 90% of oral cancer occurs in people older than 45 years Lesions of gingiva account for approximately 10% of the oral squamous cell carcinomas and may present clinically as an area of ulceration, exophytic mass, or red/white speckled patches. The proximity to the underlying periosteum may invite early bone invasion. Carcinoma of gingiva constitutes an extremely important group of neoplasms as the lesion frequently mimics the reactive and inflammatory conditions affecting the periodontium, delaying the diagnosis and making the prognosis of the patient poorer. A rare case of gingival squamous cell carcinoma has been reported here, in a 40 Year old male patient. Careful recording of the case history and results of clinical examination, radiographic, and laboratory investigations, along with a critical review of similar conditions led to the diagnosis, and treatment was initiated.

Immunohistochemical Evaluation of Glucose Transporter Type 1 in Epithelial Dysplasia and Oral Squamous Cell Carcinoma.

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Pereira, Karuza Maria Alves; Feitosa, Sthefane Gomes; Lima, Ana Thayssa Tomaz; Luna, Ealber Carvalho Macedo; Cavalcante, Roberta Barroso; de Lima, Kenio Costa; Chaves, Filipe Nobre; Costa, Fábio Wildson Gurgel

2016-01-01

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and some of these have been documented in association or preceded by oral epithelial dysplasia (OED). Aggressive cancers with fast growth have demonstrated overexpression of some glucose transporters (GLUTs). Thus, the aim of this study was to analyze the immunohistochemical expression of the glucose transporter, GLUT-1, in OEDs and OSCCs, seeking to better elucidate the biological behavior of neoplasias. Fifteen cases were selected this research of both lesions. Five areas were analyzed from each case by counting the percentage of positive cells at 400x magnification. Immunoreactivity of GLUT-1 was observed in 100% of the samples ranging from 54.2% to 86.2% for the OSCC and 73.9% to 97.4% for the OED. Statistical test revealed that there was greater overexpression of GLUT-1 in OED than the OSCC (p=0.01). It is believed the high expression of GLUT-1 may reflect the involvement of GLUT-1 in early stages of oral carcinogenesis.

Molecular profiling of tumour budding implicates TGFβ-mediated epithelial–mesenchymal transition as a therapeutic target in oral squamous cell carcinoma

DEFF Research Database (Denmark)

Jensen, David Hebbelstrup; Dabelsteen, Erik; Specht, Lena

2015-01-01

collected from oral squamous cell carcinoma (OSCC) specimens using laser capture microdissection and examined with RNA sequencing and miRNA-qPCR arrays. Compared with cells from the central parts of the tumours, budding cells exhibited a particular gene expression signature comprising factors involved...

Patients with oral cancer developing from pre-existing oral leukoplakia: do they do better than those with de novo oral cancer?

NARCIS (Netherlands)

Weijers, M.; ten Hove, I.; Allard, R.H.B.; Bezemer, D.P.D.; van der Waal, I.

2008-01-01

Background: It has been suggested that patients with squamous cell carcinomas derived from oral leukoplakia have a better prognosis than patients with carcinomas that are not associated with oral leukoplakia. Aim: To study the mortality rate of 19 patients with a squamous cell carcinoma derived from

Signal regulatory protein α associated with the progression of oral leukoplakia and oral squamous cell carcinoma regulates phenotype switch of macrophages.

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Ye, Xiaojing; Zhang, Jing; Lu, Rui; Zhou, Gang

2016-12-06

Signal regulatory protein α (SIRPα) is a cell-surface protein expressed on macrophages that are regarded as an important component of the tumor microenvironment. The expression of SIRPα in oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC), and further explored the role of SIRPα on the phenotype, phagocytosis ability, migration, and invasion of macrophages in OSCC were investigated. The expression of SIRPα in OLK was higher than in OSCC, correlating with the expression of CD68 and CD163 on macrophages. After cultured with the conditioned media of oral cancer cells, the expression of SIRPα on THP-1 cells was decreased gradually. In co-culture system, macrophages were induced into M2 phenotype by oral cancer cells. Blockade of SIRPα inhibited phagocytosis ability and IL-6, TNF-α productions of macrophages. In addition, the proliferation, migration, and IL-10, TGF-β productions of macrophages were upregulated after blockade of SIRPα. Macrophages upregulated the expression of SIRPα and phagocytosis ability, and inhibited the migration and invasion when the activation of NF-κB was inhibited by pyrrolidine dithiocarbamate ammonium (PDTC). Hence, SIRPα might play an important role in the progression of OLK and oral cancer, and could be a pivotal therapeutic target in OSCC by regulating the phenotype of macrophages via targeting NF-κB.

Peritumoral interstitial double-nuclide double-compound lymphoscintigraphy (PIDDL) in squamous cell carcinoma of the oral cavity

International Nuclear Information System (INIS)

Munz, D.L.; Jung, H.

1985-01-01

PIDDL is a new two-phase lymphoscintigraphic approach developed by MUNZ et al. for identification of lymph node drainage groups of primary tumors followed by direct visualization of metastases in the nodes. The present study was done to test the diagnostic usefulness of PIDDL in squamous cell carcinoma of the oral cavity. 58 patients of either sex, aged 31-86 years, were examined prior to surgery. In the first phase of PIDDL, lymph node groups draining the primary lesions were identified after peritumoral interstitial injection of 1.52.0 mCi Tc-99m antimony trisulfide colloid or Tc-99m human serum albumin microcolloid. In the second phase, metastases located in the draining lymph nodes were visualized following peritumoral interstitial injection of 200-300 μCi Ga-67 citrate. Ga-67 accumulated in 71% of lymph node drainage groups identified. No GA-67 uptake was observed in lymph nodes other than those identified by the radiocolloid. Based on the radiocolloid lymphoscintigraphic data, selective lymph node dissection was performed in 41 of the patients examined. The study concludes that PIDDL offers a promising approach for the noninvasive assessment of lymph node metastases in squamous cell carcinoma of the oral cavity

The significance of Epstein Barr Virus (EBV & DNA Topoisomerase II alpha (DNA-Topo II alpha immunoreactivity in normal oral mucosa, Oral Epithelial Dysplasia (OED and Oral Squamous Cell Carcinoma (OSCC

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Osman Mohamed M

2008-11-01

Full Text Available Abstract Background Head and neck cancer including oral cancer is considered to develop by accumulated genetic alterations and the major pathway is cancerization from lesions such as intraepithelial dysplasia in oral leukoplakia and erythroplakia. The relationship of proliferation markers with the grading of dysplasia is uncertain. The involvement of EBV in oral carcinogenesis is not fully understood. Aim The present study was designed to investigate the role of EBV and DNA Topoisomerase II∝ (DNA-Topo II∝ during oral carcinogenesis and to examine the prognostic significance of these protein expressions in OSCCs. Methods Using specific antibodies for EBV and DNA-Topo II∝, we examined protein expressions in archival lesion tissues from 16 patients with oral epithelial dysplasia, 22 oral squamous cell carcinoma and 20 normal oral mucosa by immunohistochemistry. Clinical information was obtained through the computerized retrospective database from the tumor registry. Results DNA-Topo II∝ was expressed in all examined specimens. Analysis of Variance ANOVA revealed highly significant difference (P 0.05 in inferior surface of tongue and in hard palatal tissues. Significant differences were observed between OEDs and NSE (P Conclusion EBV and DNA Topo II-αLI expression are possible indicators in oral carcinogenesis and may be valuable diagnostic and prognostic indices in oral carcinoma.

Correlation between podoplanin expression and extracapsular spread in squamous cell carcinoma of the oral cavity using subjective immunoreactivity scores and semiquantitative image analysis.

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Mermod, Maxime; Bongiovanni, Massimo; Petrova, Tatiana V; Dubikovskaya, Elena A; Simon, Christian; Tolstonog, Genrich; Monnier, Yan

2017-01-01

The correlation between podoplanin expression and extracapsular spread in head and neck squamous cell carcinoma (HNSCC) has never been reported. The purpose of this study was to assess the predictive value of podoplanin expression for this parameter. Subjective immunoreactivity scores and semiquantitative image analysis of podoplanin expression were performed in 67 patients with primary oral squamous cell carcinoma and in their corresponding lymph nodes. Neck classification showed 34 cases (51%) of pN0 and 33 cases (49%) of pN+. Correlation between the levels of podoplanin expression and the histopathological data was established. In lymph nodes, a high level of podoplanin expression correlated with the presence of extracapsular spread by multivariate analysis (p = .03). A strong correlation between subjective and semiquantitative image analysis was observed (r = 0.77; p < .001). A high level of podoplanin expression in lymph node metastases of oral squamous cell carcinoma is independently associated with extracapsular spread. © 2016 Wiley Periodicals, Head Neck 39: 98-108, 2017. © 2016 Wiley Periodicals, Inc.

Cisplatin, Intensity-Modulated Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

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2018-05-18

CDKN2A-p16 Negative; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity

International Nuclear Information System (INIS)

Fillies, Thomas; Werkmeister, Richard; Packeisen, Jens; Brandt, Burkhard; Morin, Philippe; Weingart, Dieter; Joos, Ulrich; Buerger, Horst

2006-01-01

Intermediary filaments are involved in cell motility and cancer progression. In a variety of organs, the expression of distinct intermediary filaments are associated with patient prognosis. In this study, we seeked to define the prognostic potential of cytokeratin and vimentin expression patterns in squamous cell carcinomas (SCC's) of the oral cavity. 308 patients with histologically proven and surgically treated squamous cell carcinomas of the oral cavity were investigated for the immunohistochemical expression of a variety of intermediary filaments including high- and low-molecular weight cytokeratins (Ck's), such as Ck 5/6, Ck 8/18, Ck 1, CK 10, Ck 14, Ck 19 and vimentin, using the tissue microarray technique. Correlations between clinical features and the expression of Cytokeratins and vimentin were evaluated statistically by Kaplan-Meier curves and multivariate Cox regression analysis. The expression of Ck 8/18 and Ck 19 were overall significantly correlated with a poor clinical prognosis (Ck 8/18 p = 0.04; Ck19 p < 0.01). These findings could also be reproduced for Ck 8/18 in primary nodal-negative SCC's and held true in multivariate-analysis. No significant correlation with patient prognosis could be found for the expression of the other cytokeratins and for vimentin. The expression of Ck 8/18 in SCC's of the oral cavity is an independent prognostic marker and indicates a decreased overall and progression free survival. These results provide an extended knowledge about the role of intermediary filament expression patterns in SCC's

HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis

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Bitu Carolina

2012-04-01

Full Text Available Abstract Background HOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer. Methods In order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA containing 127 oral squamous cell carcinomas (OSCC was performed to determine the prognostic role of HOXA1 expression. Results We showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026. Conclusion Our findings indicate that HOXA1 may contribute to oral carcinogenesis

HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis

International Nuclear Information System (INIS)

Bitu, Carolina Cavalcante; Destro, Maria Fernanda de Souza Setúbal; Carrera, Manoela; Silva, Sabrina Daniela da; Graner, Edgard; Kowalski, Luiz Paulo; Soares, Fernando Augusto; Coletta, Ricardo D

2012-01-01

HOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer. In order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT) and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA) containing 127 oral squamous cell carcinomas (OSCC) was performed to determine the prognostic role of HOXA1 expression. We showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells) decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026). Our findings indicate that HOXA1 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and suggest that HOXA1

Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer.

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Hayes, Richard B; Ahn, Jiyoung; Fan, Xiaozhou; Peters, Brandilyn A; Ma, Yingfei; Yang, Liying; Agalliu, Ilir; Burk, Robert D; Ganly, Ian; Purdue, Mark P; Freedman, Neal D; Gapstur, Susan M; Pei, Zhiheng

2018-03-01

Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC. To prospectively examine associations between the oral microbiome and incident HNSCC. This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline. Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P-value (q-value) <.10 were considered significant. Incident HNSCC. The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco

The chemopreventive properties and therapeutic modulation of green tea polyphenols in oral squamous cell carcinoma.

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Lee, Ui-Lyong; Choi, Sung-Weon

2011-01-01

Chemoprevention is a relatively novel and promising approach for controlling cancer that uses specific natural products or synthetic agents to suppress, reverse, or prevent premalignancy before transformation into invasive cancer. Oral cavity squamous cell carcinoma (OCSCC) represents a large, worldwide health burden with approximately 274,000 cases diagnosed annually worldwide. Smoking and alcohol consumption are major inducers of OCSCC. Recently, the human papilloma virus was also shown to potentially be an etiologic factor. Due to its easily identifiable risk factors and the presence of premalignant regions, oral cancer makes a good candidate for chemoprevention. Green tea is the most widely consumed beverage in the world, and it has received considerable attention because of its abundant, scientifically proven, beneficial effects on human health. In this review, we discuss the role of green tea in oral cancer chemoprevention with regard to the multiple molecular mechanisms proposed in various in vitro, in vivo, and clinical trials.

ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment

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2018-03-02

Oral Cavity Neoplasm; Oropharyngeal Neoplasm; Stage I Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage I Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage II Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage II Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

Squamous Cell Carcinoma Arising from an Oral Lichenoid Lesion: A Case Report

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Ali Taghavi Zenouz

2012-02-01

Full Text Available Lichenoid reactions represent a family of lesions with different etiologic factors and a common clinical and histologic appearance. Lichen planus is included with lichenoid reactions and is a relatively common chronic mucocutaneous disorder. The most important complication of lichenoid reactions is the possibility of malignant transformation. That is why it has been considered a precancerous condition. Although the malignant transformation rate varies widely in the literature, from 0.4 to 6.5 percent, in most studies it does not exceed 1%. The aim of this paper is to report a rare case of squamous cell carcinoma (SCC arising within an oral lichenoid lesion in a 17-year-old woman, where SCC is very uncommon. The patient did not have any risk factors and was healthy. The lesion was located on the border of the tongue. In view of the common occurrence of OLP (oral lichen planus and the unresolved issues regarding its premalignant potential, this case report illustrates the need for histologic confirmation and a close follow-up of clinical lesions with lichenoid features.

Phase 1b Food Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer.

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2018-03-05

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage 0 Hypopharyngeal Cancer; Stage 0 Laryngeal Cancer; Stage 0 Lip and Oral Cavity Cancer; Stage 0 Nasopharyngeal Cancer; Stage 0 Oropharyngeal Cancer; Stage 0 Paranasal Sinus and Nasal Cavity Cancer; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Salivary Gland Cancer; Stage II Squamous Cell Carcinoma of the Hypopharynx; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Nasal Cavity and Paranasal Sinus Cancer; Stage IVA

Photodynamic Therapy Using Temoporfin Before Surgery in Treating Patients With Recurrent Oral Cavity or Oropharyngeal Cancer

Science.gov (United States)

2014-09-02

Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Determination of ABO blood grouping from human oral squamous epithelium by the highly sensitive immunohistochemical staining method EnVision+.

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Noda, Hiroshi; Yokota, Makoto; Tatsumi, Shinji; Sugiyama, Shizuyuki

2002-03-01

Using the highly sensitive immunohistochemical staining method EnVision+, which employs a dextran polymer reagent for the secondary antibody, the detection of the ABH antigens was attempted in the oral squamous epithelium. This new technique uses monoclonal antibody as a primary antibody and it takes about three hours for staining. The time is much shorter than conventional absorption-elution testing or absorption-inhibition testing for the determination of ABO blood grouping. Secretor saliva samples were stained at strong intensity by the antibody, which corresponded to its blood group and anti-H. On the one hand, nonsecretor saliva samples were stained at strong intensity only by the antibody that corresponded to its blood group, and at weak intensity only by anti-H. Since human oral squamous epithelium antigens were stained specifically by this method, we can examine the ABO blood group of saliva samples and perform cytodiagnosis at the same time. Our research suggested that the EnVision+ Method is a useful technique for ABO blood grouping of saliva in forensic cases.

Comparison of oropharyngeal and oral cavity squamous cell cancer incidence and trends in New Zealand and Queensland, Australia.

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Elwood, J Mark; Youlden, Danny R; Chelimo, Carol; Ioannides, Sally J; Baade, Peter D

2014-02-01

Increases in the incidence of squamous cell oropharyngeal cancer (OPC) have been reported from some countries, but have not been assessed in Australia or New Zealand. This study examines trends for squamous cell OPC and squamous cell oral cavity cancer (OCC) in two similarly sized populations, New Zealand and Queensland, Australia. Incidence data for 1982-2010 were obtained from the respective population-based cancer registries for squamous cell OPC and OCC, by subsite, sex, and age. Time trends and annual percentage changes (APCs) were assessed by joinpoint regression. The incidence rates of squamous cell OPC in males in New Zealand since 2005 and Queensland since 2006 have increased rapidly, with APCs of 11.9% and 10.6% respectively. The trends were greatest at ages 50-69 and followed more gradual increases previously. In females, rates increased by 2.1% per year in New Zealand from 1982, but by only 0.9% (not significant) in Queensland. In contrast, incidence rates for OCC decreased by 1.2% per year in males in Queensland since 1982, but remained stable for females in Queensland and for both sexes in New Zealand. Overall, incidence rates for both OCC and OPC were substantially higher in Queensland than in New Zealand. In males in both areas, OPC incidence is now higher than that of OCC. Incidence rates of squamous cell OPC have increased rapidly in men, while rates of OCC have been stable or reducing, showing distinct etiologies. This has both clinical and public health importance, including implications for the extension of human papilloma virus (HPV) vaccination to males. Copyright © 2014 Elsevier Ltd. All rights reserved.

Marital status and survival of patients with oral cavity squamous cell carcinoma: a population-based study

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Shi, Xiao; Zhang, Ting-ting; Hu, Wei-ping; Ji, Qing-hai

2017-01-01

Background The relationship between marital status and oral cavity squamous cell carcinoma (OCSCC) survival has not been explored. The objective of our study was to evaluate the impact of marital status on OCSCC survival and investigate the potential mechanisms. Results Married patients had better 5-year cancer-specific survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs 41.1%). In multivariate Cox regression models, unmarried patients also showed higher mortality risk ...

Immunocompromised and immunocompetent mouse models for head and neck squamous cell carcinoma

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Lei ZG

2016-01-01

Full Text Available Zhen-ge Lei,1,* Xiao-hua Ren,2,* Sha-sha Wang,3 Xin-hua Liang,3,4 Ya-ling Tang3,5 1Department of Oral and Maxillofacial Surgery, Stomatological Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, 2Department of Stomatology, Sichuan Medical Science Academy and Sichuan Provincial People’s Hospital, 3State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 4Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, 5Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Abstract: Mouse models can closely mimic human oral squamous epithelial carcinogenesis, greatly expand the in vivo research possibilities, and play a critical role in the development of diagnosis, monitoring, and treatment of head and neck squamous cell carcinoma. With the development of the recent research on the contribution of immunity/inflammation to cancer initiation and progression, mouse models have been divided into two categories, namely, immunocompromised and immunocompetent mouse models. And thus, this paper will review these two kinds of models applied in head and neck squamous cell carcinoma to provide a platform to understand the complicated histological, molecular, and genetic changes of oral squamous epithelial tumorigenesis. Keywords: head and neck squamous cell carcinoma, HNSCC, mouse models, immunocompromised models, immunocompetent models, transgenic models

Radiological imaging of the neck for initial decision-making in oral squamous cell carcinomas-A questionnaire survey in the Nordic countries

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Norling, Rikke; Grau, Cai; Nielsen, Michael B

2012-01-01

by palpation and diagnostic imaging of the neck. We investigated the current practice of the initial radiological work-up of patients with oral squamous cell carcinomas (OSCC) in the Nordic countries. Methods. A questionnaire regarding the availability and use of guidelines and imaging modalities...

The prognostic implication of the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in primary locally advanced oral squamous cell carcinoma cases: a tissue microarray study.

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Solomon, Monica Charlotte; Vidyasagar, M S; Fernandes, Donald; Guddattu, Vasudev; Mathew, Mary; Shergill, Ankur Kaur; Carnelio, Sunitha; Chandrashekar, Chetana

2016-12-01

Oral squamous cell carcinomas comprise a heterogeneous tumor cell population with varied molecular characteristics, which makes prognostication of these tumors a complex and challenging issue. Thus, molecular profiling of these tumors is advantageous for an accurate prognostication and treatment planning. This is a retrospective study on a cohort of primary locally advanced oral squamous cell carcinomas (n = 178) of an Indian rural population. The expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in a cohort of primary locally advanced oral squamous cell carcinomas was evaluated. A potential biomarker that can predict the tumor response to treatment was identified. Formalin-fixed paraffin-embedded tumor blocks of (n = 178) of histopathologically diagnosed cases of locally advanced oral squamous cell carcinomas were selected. Tissue microarray blocks were constructed with 2 cores of 2 mm diameter from each tumor block. Four-micron-thick sections were cut from these tissue microarray blocks. These tissue microarray sections were immunohistochemically stained for EGFR, p53, Bcl-2, cyclin D1 and p16. In this cohort, EGFR was the most frequently expressed 150/178 (84%) biomarker of the cases. Kaplan-Meier analysis showed a significant association (p = 0.038) between expression of p53 and a poor prognosis. A Poisson regression analysis showed that tumors that expressed p53 had a two times greater chance of recurrence (unadjusted IRR-95% CI 2.08 (1.03, 4.5), adjusted IRR-2.29 (1.08, 4.8) compared with the tumors that did not express this biomarker. Molecular profiling of oral squamous cell carcinomas will enable us to categorize our patients into more realistic risk groups. With biologically guided tumor characterization, personalized treatment protocols can be designed for individual patients, which will improve the quality of life of these patients.

Prognostic value of HMGA2, P16, and HPV in oral squamous cell carcinomas

DEFF Research Database (Denmark)

Loeschke, S.; Ohlmann, A. K.; Bräsen, Jan Hinrich

2016-01-01

Purpose Molecular markers are only occasionally used in diagnostics of oral squamous cell carcinoma (OSCC), even though they could influence decision making in individually designed cancer therapies. We analyzed the predictive value of the markers HPV, p16, and HMGA2 and the TNM classification...... in regard to survival and recurrence rates. Material and methods A total of 91 OSCC cases were included in this study, with a follow up of up to 131 months. HPV-DNA was present in 7 carcinomas. p16 was detected by immunohistochemical staining in 14 samples. HMGA2 expression was determined by real...

The Prevalence of Human Papilloma Virus in Squamous Cell Carcinoma of Oral Tongue.

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Ashraf, Mohamad Javad; Hosseini, Shahla; Monabati, Ahmad; Valibeigi, Behnaz; Khademi, Bijan; Abedi, Elham; Azarpira, Negar

2017-01-01

Oral tongue Squamous Cell carcinoma (SCC) commonly involves males between the sixth to eighth decades of life. Major risk factors are tobacco usage and alcohol consumption. The increasing number of patients developing oral tongue cancer without these well-known risk factors suggests that a viral infection, such as Human Papillomavirus (HPV), may be responsible for this increase, by acting as an oncogenic agent. This study investigated the prevalence of HPV infection and its clinicopathologic significance in oral tongue SCCs. Tissue blocks from a total of 50 cases (patients with oral tongue SCC) and 50 controls (palatine tonsillar tissues with benign diagnosis) were selected. DNA was extracted from tumoral and non-tumoral tissue blocks. Detection of common HPV DNA by nested Polymerase Chain Reaction (PCR), and high-risk genotypes, HPV 16 and HPV 18, by conventional PCR, was achieved and the results correlated with clinicopathological parameters. Of the 50 patients (18 males and 32 females with a mean age of 57.36±12.18 years, and age range of 27 to 86 years), 7 (14%) had HPV positive results. None of the control group subjects had HPV DNA positive results (P-value of 0.012). The HPV genotype 16/18 was not detected in positive cases. No statistically significant association was found between HPV status and gender, age, tumor grade, tumor stage or lymph node involvement. Although there was a significantly higher prevalence of HPV in oral tongue SCC, its association with carcinogenesis in this area requires further studies.

Conventional clinical and prognostic variables in 150 oral squamous cell carcinoma cases from the indigenous population of Karachi.

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Alamgir, Muhammad Mohiuddin; Jamal, Qamar; Mirza, Talat

2016-01-01

To analyze clinical and prognostic variables of Oral Squamous Cell Carcinoma (OSCC) cases from the indigenous population of Karachi and to correlate with the common risk factor of tobacco habit. The study was conducted at Ziauddin University, Karachi. One hundred fifty OSCC cases were collected from the Oncology Department of Ziauddin University Hospital, North Nazimabad, Karachi and Otolaryngology ward of Civil Hospital, Karachi, during 2011 and 2015. The reporting included demographic details and variables like intra-oral subsites, clinical stage and histological grade. Recurrence of tumor after initial resection was also documented. The patient's population comprised of 98 males and 52 females. The mean age was 47.1± 12.22 (range:20-78 years). Maximum numbers were seen in the 41-50 years age group. Urdu-speaking community was the most affected ethnic group (n=75). Clinico-pathological analysis revealed that majority of cases were moderately differentiated (59%) and were either clinical stage II (35%) or IV (29%) tumors. The most common intra-oral subsite came out to be buccal mucosa of cheeks (56%) followed by lateral borders of tongue (21%), lips (13%), alveolar (6%), palate (2.6%) floor of mouth (1.3%), etc. Recurrence was observed in 08 out of 150 cases. All patients underwent primary resection±neck dissection and reconstruction where possible. Overall experience with oral squamous cell carcinoma shows that it has a high tendency for local invasion as well as dissemination to regional lymph nodes, i.e. cervical lymph nodes, both are associated with a poor prognosis. Preventable risk factor of tobacco chewing has been observed in majority of these cases.

CD133 expression in oral lichen planus correlated with the risk for progression to oral squamous cell carcinoma.

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Sun, Lili; Feng, Jinqiu; Ma, Lihua; Liu, Wei; Zhou, Zengtong

2013-12-01

Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk for progression to oral squamous cell carcinoma (OSCC). The objective of this study to determine protein expression of cancer stem cell marker CD133 in tissue samples of patients with OLP and evaluate the correlation between CD133 expression and the risk of progression to OSCC. In this longitudinal case-control study, a total of 110 patients with OLP who received a mean follow-up of 56 months were enrolled, including 100 patients who did not progress to OSCC and 10 patients who had progressed to OSCC. CD133 expression was determined using immunohistochemistry in samples from these patients. Analysis of 10 cases of normal oral mucosa and 6 cases of postmalignant OSCC form previously diagnosed OLP was also performed. The results showed that CD133 expression was observed in 29% cases of nonprogressing OLP and in 80% cases of progressing OLP (P = .002). CD133 was not expressed in normal oral mucosa, but it positively expressed in the 100% cases of OSCC. Logistic regression analysis revealed that the risk of malignant progression in the patients with CD133-positive expression was significantly higher than those with CD133 negativity (odds ratio, 9.79; 95% confidence interval, 1.96-48.92; P = .005). Collectively, CD133 expression was significantly associated with malignant progression in a longitudinal series of patients with OLP. Our findings suggested that CD133 may serve as a novel candidate biomarker for risk assessment of malignant potential of OLP. © 2013.

Comparison of staining of mitotic figures by haematoxylin and eosin-and crystal violet stains, in oral epithelial dysplasia and squamous cell carcinoma

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Ankle Madhuri

2007-01-01

Full Text Available Mitosis of cells gives rise to tissue integrity. Defects during mitosis bring about abnormalities. Excessive proliferation of cells due to increased mitosis is one such outcome, which is the hallmark in precancer and cancer. The localization of proliferating cells or their precursors may not be obvious and easy. Establishing an easy way to distinguish these mitotic cells will help in grading and understanding their biological potential. Although immunohistochemistry is an advanced method in use, the cost and time factor makes it less feasible for many laboratories. Selective histochemical stains like toluidine blue, giemsa and crystal violet have been used in tissues including the developing brain, neural tissue and skin. Aim of the study: 1To compare the staining of mitotic cells in haematoxylin and eosin with that in crystal violet. 2To compare the number of mitotic figures present in normal oral mucosa, epithelial dysplasia and oral squamous cell carcinoma in crystal violet-stained sections with that in H and E-stained sections. Materials and Methods: Ten tissues of normal oral mucosa and 15 tissues each of oral epithelial dysplasia seen in tobacco-associated leukoplakia and squamous cell carcinoma were studied to evaluate the selectivity of 1% crystal violet for mitotic figures. The staining was compared with standard H and E staining. Statistical analysis was done using Man-Whitney U test. Results: A statistically significant increase in the mean mitotic count was observed in crystal violet-stained sections of epithelial dysplasia as compared to the H and E-stained sections ( p = 0.0327. A similar increase in the mitotic counts was noted in crystal violet-stained sections of oral squamous cell carcinoma as compared to the H and E-stained sections.( p = 0.0443. No significant difference was found in the mitotic counts determined in dysplasia or carcinoma by either the crystal violet ( p = 0.4429 or the H and E-staining techniques ( p = 0

Dysregulation of heat shock protein 27 expression in oral tongue squamous cell carcinoma

International Nuclear Information System (INIS)

Wang, Anxun; Liu, Xiqiang; Sheng, Shihu; Ye, Hui; Peng, Tingsheng; Shi, Fei; Crowe, David L; Zhou, Xiaofeng

2009-01-01

Recent proteomic studies identified Hsp27 as a highly over-expressed protein in oral squamous cell carcinoma (OSCC). Clinical studies that attempted to evaluate the prognostic values of Hsp27 yielded inconsistent results, which may be due to inclusion of OSCC cases from multiple anatomic sites. In this study, to determine the utility of Hsp27 for prognosis, we focused on oral tongue SCC (OTSCC), one of the most aggressive forms of OSCC. Archival clinical samples of 15 normal oral tongue mucosa, 31 dysplastic lesions, 80 primary OTSCC, and 32 lymph node metastases were examined for Hsp27 expression by immunohistochemistry (IHC). Statistical analyses were carried out to assess the prognostic value of Hsp27 expression for patients with this disease. Dysregulation of Hsp27 expression was observed in dysplastic lesions, primary OTSCC, and lymph node metastases, and appears to be associated with disease progression. Statistical analysis revealed that the reduced Hsp27 expression in primary tumor tissue was associated with poor differentiation. Furthermore, the higher expression of Hsp27 was correlated with better overall survival. Our study confirmed that the dysregulation of Hsp27 expression is a frequent event during the progression of OTSCC. The expression of Hsp27 appears to be an independent prognostic marker for patients with this disease

Expression of GLUT1 in stratified squamous epithelia and oral carcinoma from humans and rats

DEFF Research Database (Denmark)

Voldstedlund, M; Dabelsteen, Erik

1997-01-01

mucosa from rat and man, and a human oral carcinoma by indirect immunofluorescence microscopy. The results showed that GLUT1 was expressed in the basal and parabasal layers of the different stratified squamous epithelia, with some variations between keratinized and non-keratinized subtypes. GLUT1...... was also expressed in ductal- and myoepithelial cells of minor salivary glands and perineural sheath located in the lamina propra, and furthermore in the cells of an oral carcinoma. GLUT4 was not expressed in any of the tissues examined. This distribution of GLUT1 does not fit with the idea of GLUT1......Most cells express facilitative glucose transporters. Four isoforms (GLUT1-4) transporting D-glucose across the plasma membrane show a specific tissue distribution, which is the basis for tissue-specific patterns in glucose metabolism. GLUT1 is expressed at high levels in tissue barriers...

Collision Tumour of Squamous Cell Carcinoma and Malignant Melanoma in the Oral Cavity of a Dog.

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Rodríguez, F; Castro, P; Ramírez, G A

2016-05-01

A 7-year-old, male cocker spaniel was presented with a gingival proliferative lesion in the rostral maxilla and enlargement of the regional lymph node. Morphological and immunohistochemical analysis revealed a collision tumour composed of two malignant populations, epithelial and melanocytic, with metastasis of the neoplastic melanocytes to the regional lymph node. The epithelial component consisted of trabeculae and islands of well-differentiated squamous epithelium immunoreactive to cytokeratins. The melanocytic component had a varying degree of pigmentation of polygonal and spindle-shaped cells, growing in nests or densely packed aggregates and immunolabelled with S100, melanoma-associated antigen (melan A), neuron-specific enolase and vimentin antibodies. Protein markers involved in tumorigenesis or cell proliferation (i.e. COX-2, p53, c-kit and Ki67), were overexpressed by the neoplastic cells. To the authors' knowledge, this is the first description of an oral collision tumour involving malignant melanoma and squamous cell carcinoma in the dog. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pulmonary squamous cell carcinoma following head and neck squamous cell carcinoma: Metastasis or second primary?

NARCIS (Netherlands)

Geurts, Tom W.; Nederlof, Petra M.; van den Brekel, Michiel W. M.; van't Veer, Laura J.; de Jong, Daphne; Hart, August A. M.; van Zandwijk, Nico; Klomp, Houke; Balm, Alfons J. M.; van Velthuysen, Marie-Louise F.

2005-01-01

Purpose: To distinguish a metastasis from a second primary tumor in patients with a history of head and neck squamous cell carcinoma and subsequent pulmonary squamous cell carcinoma. Experimental Design: For 44 patients with a primary squamous cell carcinoma of the head and neck followed by a

Squamous Cell Carcinoma Arising from Inverted Schneiderian Papilloma: A Case Report with Oral Involvement

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Alexandre Simões Garcia

2014-01-01

Full Text Available Inverted Schneiderian papilloma is an uncommon benign tumor that presents tendency to recur and propensity to be associated with malignancy in approximately 10% of the cases. Some of these lesions are isolated in the maxillary sinus, and predominantly affect white males with mean age of 50 years. We report a case of squamous cell carcinoma arising from inverted Schneiderian papilloma in the maxillary sinus extending to the mouth. The patient was submitted to extraction of a maxillary molar tooth four months before the exacerbation of the symptoms of nasal airway obstruction and facial enlargement. Computed tomography scan revealed a sinonasal mass causing opacification of the right maxillary sinus with destruction of the lateral nasal wall and maxillary sinus floor. The patient was referred to an oncology center for treatment and died from tumor progression one year after the cancer was diagnosed. The intention of this report is to alert dentists to include the inverted Schneiderian papilloma, either associated with squamous cell carcinoma, or not, in the differential diagnosis of maxillary sinus tumors with aggressive behavior, which may extend to the oral cavity or involve roots of teeth.

Evaluation of Serum IgA level in nontreated and treated oral squamous cell carcinoma patients

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Richa Mishra

2018-01-01

Full Text Available Introduction: Research in early cancer detection has led to discovery of many immunological tumor markers that contribute considerably to supplement the method of diagnosis. High serum immunoglobulin A (IgA values in patients with cancer have been used as tumor markers. Aims and Objectives: To evaluate and compare the serum IgA levels in nontreated, treated oral squamous cell carcinoma (SCC patients, and control group. Materials and Methods: A total of 60 patients were included in the study. 20 biopsy confirmed oral SCC patients, who have received no medical treatment, 20 oral SCC patients treated with surgery and/or radiotherapy and 20 normal healthy individuals. Venous blood samples were collected from anterior cubital vein and were delivered to the biochemistry laboratory for the estimation of serum IgA level by nephelometry method. Statistical Analysis Used: Statistical method employed were the Pearson's Chi-square test and One-way analysis of variance (Welch followed by Games-Howell post-hoc test. Results: We observed significant difference for serum IgA between study subjects in control, nontreated and treated oral SCC patients (P < 0.001. Serum IgA level in nontreated group was significantly higher than treated group and there was an approximately two-fold increase in serum IgA level in nontreated oral SCC patients when compared to that of the normal healthy individuals. Conclusion: Serum level of IgA might be employed as diagnostic and prognostic indicators in oral cancer.

Clinical significance of Keap1 and Nrf2 in oral squamous cell carcinoma.

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Cong-Fa Huang

Full Text Available Oxidative stress has been reported to play an important role in progression and prognostication in various kinds of cancers. However, the role and clinical significance of oxidative stress markers Keap1 and Nrf2 in oral squamous cell carcinoma (OSCC has not been elucidated. This study aimed to investigate the correlation of oxidative stress markers Keap1 and Nrf2 expression and pathological features in OSCC by using tissue microarray. Tissue microarrays containing 17 normal oral mucosa, 7 oral epithelial dysplasia and 43 OSCC specimens were studied by immunohistochemistry. The association among these proteins and pathological features were analyzed. Expression of oxidative stress markers Keap1, Nrf2, and antioxidants PPIA, Prdx6, as well as CD147 was found to increase consecutively from normal oral mucosa to OSCC, and the Keap1, Nrf2, PPIA, Prdx6, CD147 expression in OSCC were significantly higher when compared to normal oral mucosa. Expression of Keap1, Nrf2 in tumors was not found to be significantly associated with T category, lymph node metastases, and pathological grade. Furthermore, we checked the relationship among these oxidative stress markers and found that Keap1 was significantly correlated with Nrf2, Prdx6 and CD147. Significant relationship between Nrf2 and Prdx6 was also detected. Finally, we found patients with overexpression of Keap1 and Nrf2 had not significantly worse overall survival by Kaplan-Meier analysis. These findings suggest that ROS markers are associated with carcinogenesis and progression of OSCC, which may have prognostic value and could be regarded as potential therapeutic targets in OSCC.

Ten-year clinico-statistical study of oral squamous cell carcinoma

International Nuclear Information System (INIS)

Aoki, Shinjiro; Kawabe, Ryoichi; Chikumaru, Hiroshi; Saito, Tomokatsu; Hirota, Makoto; Miyake, Tetsumi; Omura, Susumu; Fujita, Kiyohide

2003-01-01

This clinico-statistical study includes 232 cases of oral squamous cell carcinoma that underwent radical treatment in the Department of Oral and Maxillofacial Surgery, Yokohama City University Hospital, during the decade from 1991 to 2000. Surgery was principally adopted as the first line for treatment in 199 cases, and radiotherapy in 33 cases. The 5-year overall survival rate was 73.4%. The results according to stage were as follows: stage I, 87.5%; Stage II, 77.9%; Stage III, 63.5%; and Stage IV A, 44.7%. The primary sites were classified as follows: upper gingiva, 85.2%; tongue, 73.7%; floor of mouth, 68.9%; lower gingiva, 66.3%; buccal mucosa, 63.9%; and hard palate, 50%. For tongue cancer, the 5-year overall survival rates by stage were: Stage I, 90.8%; Stage II, 82.1%; Stage III, 40.3%; and Stage IV A, 45.7%. Statistical significance was seen between cases of Stages I and II and those of Stages III and IV A stage. For lower gingival cancer, the 5-year overall survival rates by stage were: Stage I, 90.8%; Stage II, 82.1%; Stage III, 40.3%; and Stage IV A, 45.7%. Even in Stage I lower gingival cancers had unfavorable clinical outcomes. Preventive neck dissections were performed on 52 N 0 neck patients, but clinically negative nodes however showed metastasis in 14 patients (26.9%). (author)

Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma.

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De Paz, Dante; Kao, Huang-Kai; Huang, Yenlin; Chang, Kai-Ping

2017-08-10

Prognosis of advanced oral squamous cell carcinoma remains a challenge for clinicians despite progress in its diagnosis and treatment over the past decades. In this review, we assessed clinicopathological factors and potential biomarkers along with their prognostic relevance in an attempt to develop optimal treatment strategies for these patients. In addition to several pathologic factors that have been proposed to improve prognostic stratification and treatment planning in the eighth edition of the American Joint Committee staging manual on cancer, we reviewed some other imaging and clinicopathological parameters demonstrated to be closely associated with patient prognosis, along with the biomarkers related to novel target or immune therapy. Evaluation of current literature regarding the prognostic stratification used in contemporary clinicopathological studies and progress in the development of targeted or immune therapy may help these patients benefit from tailored and personalized treatment and obtain better oncological results.

Role of human papilloma virus infection and oral-genital contact in oral cancer ethiopathogenesis.

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Stanko, P; Kruzliak, P; Labas, P

2013-01-01

Head and neck squamous cell carcinoma and especially oropharyngeal squamous cell carcinoma is a very significant cause of morbidity and mortality. The majors risk factors of these tumors are tobacco smoking, chewing and alcohol consumption. But there is a group, non-drinking and non-smoking, patients with oropharyngeal squamous cell carcinoma. In these patients may be oral-genital contact and human papillomavirus infection the major risk factor for oral carcinogenesis. Aim of this review is to point out this fact in correlation with clinical studies and clinical conclusion for medical practice (Fig. 1, Ref. 32).

Squamous cell carcinoma of the oral cavity; An unselected material from a 5-year period

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Lindeloev, B.; Kirkegaard, J.; Hansen, H.S. (Copenhagen Univ. Hospital (Denmark). Dept. of Head and Neck Oncology Copenhagen Univ. Hospital (Denmark). Dept. of Otolaryngology)

1990-01-01

Three hundred and four patients with squamous cell carcinomas of the oral cavity were treated at the Finsen Institute in cooperation with the ENT-surgical departments between 1978 and 1982. The primary treatment consisted of radiotherapy alone in 74%, surgery alone in 4%, and a combination of radiotherapy and surgery in 15% of the patients. 2% received other treatment (cryotherapy), 5% did not complete the planned radiotherapy, and 1% were not treated at all. Of 203 patients with tumour remnant or first recurrence, 45% were operated, 2% received radiotherapy, and 2% combined treatment. This treatment strategy made 38% of the patients free of disease in the follow-up period (3 1/2 to 8 years) or until the patients died from other causes. Fifty-nine percent of the patients died from their oral carcinomas. Tumour size (T), lymph node status (N), and tumour stage were as expected important prognostic factors. (orig.).

Prediction of occult lymph node metastasis in squamous cell carcinoma of the oral cavity and the oropharynx using peritumoral Prospero homeobox protein 1 lymphatic nuclear quantification.

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Mermod, Maxime; Bongiovanni, Massimo; Petrova, Tatiana V; Dubikovskaya, Elena A; Simon, Christian; Tolstonog, Genrich; Monnier, Yan

2016-09-01

The use of lymphatic vessel density as a predictor of occult lymph node metastasis (OLNM) in head and neck squamous cell carcinoma (HNSCC) has never been reported. Staining of the specific lymphatic endothelial cells nuclear marker, PROX1, as an indicator of lymphatic vessel density was determined by counting the number of positive cells in squamous cell carcinomas (SCCs) of the oral cavity and the oropharynx with clinically negative necks. Correlation with histopathological data was established. Peritumoral PROX1 lymphatic nuclear count significantly correlated with the detection of OLNM in multivariate analysis (p oral cavity and the oropharynx allows accurate prediction of occult lymph node metastasis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1407-1415, 2016. © 2016 Wiley Periodicals, Inc.

Long non-coding RNA TUG1 promotes progression of oral squamous cell carcinoma through upregulating FMNL2 by sponging miR-219

OpenAIRE

Yan, Guangqi; Wang, Xue; Yang, Mingliang; Lu, Li; Zhou, Qing

2017-01-01

Oral squamous cell carcinoma (OSCC) is a prevalent oral disease with a high morbidity and mortality rate. Several long non-coding RNAs (lncRNAs) were identified as important regulators of carcinogenesis. However, the pathogenic implications of TUG1 in OSCC are still unclear. In the present study, the expression of TUG1 was increased in OSCC cells. Knockdown of TUG1 inhibited cell proliferation, migration, and invasion, and induced cell cycle arrest at G0/G1 phase, whereas overexpression of TU...

Notch Signaling Activation Is Associated with Patient Mortality and Increased FGF1-Mediated Invasion in Squamous Cell Carcinoma of the Oral Cavity.

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Weaver, Alice N; Burch, M Benjamin; Cooper, Tiffiny S; Della Manna, Deborah L; Wei, Shi; Ojesina, Akinyemi I; Rosenthal, Eben L; Yang, Eddy S

2016-09-01

Oral squamous cell carcinoma (OSCC) is a cancer subtype that lacks validated prognostic and therapeutic biomarkers, and human papillomavirus status has not proven beneficial in predicting patient outcomes. A gene expression pathway analysis was conducted using OSCC patient specimens to identify molecular targets that may improve management of this disease. RNA was isolated from 19 OSCCs treated surgically at the University of Alabama at Birmingham (UAB; Birmingham, AL) and evaluated using the NanoString nCounter system. Results were confirmed using the oral cavity subdivision of the Head and Neck Squamous Cell Carcinoma Cancer (HNSCC) study generated by The Cancer Genome Atlas (TCGA) Research Network. Further characterization of the in vitro phenotype produced by Notch pathway activation in HNSCC cell lines included gene expression, proliferation, cell cycle, migration, invasion, and radiosensitivity. In both UAB and TCGA samples, Notch pathway upregulation was significantly correlated with patient mortality status and with expression of the proinvasive gene FGF1 In vitro Notch activation in HNSCC cells increased transcription of FGF1 and induced a marked increase in cell migration and invasion, which was fully abrogated by FGF1 knockdown. These results reveal that increased Notch pathway signaling plays a role in cancer progression and patient outcomes in OSCC. Accordingly, the Notch-FGF interaction should be further studied as a prognostic biomarker and potential therapeutic target for OSCC. Patients with squamous cell carcinoma of the oral cavity who succumb to their disease are more likely to have upregulated Notch signaling, which may mediate a more invasive phenotype through increased FGF1 transcription. Mol Cancer Res; 14(9); 883-91. ©2016 AACR. ©2016 American Association for Cancer Research.

Correlation of human papilloma virus with oral squamous cell carcinoma in Chinese population.

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Zhou, Jingping; Tao, Detao; Tang, Daofang; Gao, Zhenlin

2015-01-01

Previous studies indicated that oral squamous cell carcinomas (OSCC) might be related to human papilloma virus (HPV) infection. However, the relationship between OSCC in a Chinese population and oral HPV infection is still unclear. In this study, we evaluate the relationship of OSCC with HPV infection in a Chinese population via a meta-analysis. The reports on HPV and OSCC in a Chinese population published between January, 1994, and October, 2015 were retrieved via CNKI/WANFANG/pubmed databases. According to the inclusion criteria, we selected 26 eligible case-control studies. After testing the heterogeneity of the studies by the Cochran Q test, the meta-analyses for HPV and HPV16 were performed using the random effects model. Quantitative meta-analyses showed that, compared with normal oral mucosa the combined odds ratio of OSCC with HPV infection were 1.98 (95% CI: 1.34-2.92). The test for overall effect showed that the P value was less than 0.05 (Z = 3.46). Forest plot analyses were seen in Figures 2 and 3. Publication bias and bias risk analysis using RevMan 5.3 software were measured indicators of the graphics of the basic symmetry. High incidences of HPV infection were found in the samples of Chinese OSCC. For the Chinese population, HPV infection elevates the risk of OSCC tumorigenesis.

A rare case of extremely high counts of circulating tumor cells detected in a patient with an oral squamous cell carcinoma

International Nuclear Information System (INIS)

Wu, Xianglei; Mastronicola, Romina; Tu, Qian; Faure, Gilbert Charles; De Carvalho Bittencourt, Marcelo; Dolivet, Gilles

2016-01-01

Despite aggressive regimens, the clinical outcome of head and neck squamous cell carcinoma remains poor. The detection of circulating tumor cells could potentially improve the management of patients with disseminated cancer, including diagnosis, treatment strategies, and surveillance. Currently, CellSearch ® is the most widely used and the only Food and Drug Administration-cleared system for circulating tumor cells detection in patients with metastatic breast, colorectal, or prostate cancer. In most cases of head and neck squamous cell carcinoma, only low counts of circulating tumor cells have been reported. A 56-year-old white male with no particular medical history, was diagnosed with a squamous cell carcinoma of oral cavity. According to the imaging results (computed tomography and 18 F-fluorodeoxyglucose positron emission tomography / computed tomography) and panendoscopy, the TNM staging was classified as T4N2M0. A non-interruptive pelvimandibulectomy was conducted according to the multidisciplinary meeting advices and the postoperative observations were normal. The patient complained of a painful cervical edema and a trismus 6 weeks after the surgery. A relapse was found by computed tomography and the patient died two weeks later. The search for circulating tumor cells in peripheral venous blood by using the CellSearch ® system revealed a very high count compared with published reports at three time points (pre-operative: 400; intra-operative: 150 and post-operative day 7: 1400 circulating tumor cells). Of note, all detected circulating tumor cells were epidermal growth factor receptor negative. We report here for the first time a rare case of oral squamous cell carcinoma with extremely high circulating tumor cells counts using the CellSearch ® system. The absolute number of circulating tumor cells might predict a particular phase of cancer development as well as a poor survival, potentially contributing to a personalized healthcare

Expression of MMP-1/PAR-1 and patterns of invasion in oral squamous cell carcinoma as potential prognostic markers

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Fan HX

2015-07-01

Full Text Available Hai-Xia Fan,1 Yan Chen,1 Bo-Xiong Ni,1 Shan Wang,1 Miao Sun,2 Dong Chen,2 Jin-Hua Zheng11Department of Anatomy, Basic Medical Science College, 2Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Harbin Medical University, Harbin, People’s Republic of ChinaBackground: Matrix metalloproteinase (MMP-1 degrades type I collagen of the extracellular matrix and also activates protease activated receptor (PAR-1 to induce angiogenesis. The aims of this study were to evaluate microvessel density (MVD and the expression of PAR-1 and MMP-1 in oral squamous cell carcinoma (SCC specimens with different patterns of invasion (POI and to evaluate their association with clinical outcomes.Methods: Seventy-four surgically obtained oral SCC samples were classified by POI according to hematoxylin-eosin staining. MVD and the localization and intensity of PAR-1 and MMP-1 expression were detected by immunohistochemistry.Results: Of the 74 oral SCC samples, 18, 5, 34, and 17 showed type I, II, III, and IV POI, respectively. MVD and expression levels of MMP-1 and PAR-1 differed between POI types I–II and POI types III–IV. Patients with low tumor expression of MMP-1 and PAR-1 and low MVD had a longer survival time than those with high tumor expression of MMP-1 and PAR-1. Moreover, the survival time of patients with POI types III–IV was shorter than that of patients with POI types I–II.Conclusion: POI combined with expression levels of MMP-1 and PAR-1 may be a valuable tool for assessing the clinical prognosis of patients with oral SCC.Keywords: oral squamous cell carcinoma, pattern of invasion, immunohistochemistry, clinical outcomes

Comparative Evaluation of the Mast Cells between Oral and Cutaneous Squamous Cell Carcinoma

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E Mohammadnia Sarvi

2017-04-01

Full Text Available BACKGROUND AND OBJECTIVE: It has been mentioned that mast cells may help to tumor invasion. According to different aggressive behavior of oral squamous cell carcinoma (OSCC compared to cutaneous SCC (CSCC, the aim of this study was to compare mast cells count between OSCC and CSCC to understand the role of them in different biologic behavior of these two tumors. METHODS: This cross-sectional study consisted of 90 samples including 30 cases of OSCC, 30 cases of CSCC, 15 cases of normal skin and 15 cases of normal oral mucosa (as control groups. Number of mast cells was counted under light microscope in 10 successive fields in invasive front of OSCCs and CSCCs at 400X magnification and mean mast cells count/mm2 were calculated and compared between studied groups using one way ANOVA statistical test. FINDINGS: Mean mast cells count in CSCC, OSCC, normal skin and normal oral mucosa groups were 20.31±14.67, 10.41±8.01, 5.10±8.67 and 4.87±2.68, respectively. There were significant differences in mast cell count between CSCC and normal skin groups (p<0.001 and between CSCC and OSCC groups (p=0.002. This difference wasn’t significant between OSCC and normal oral mucosa groups (p=0.337. CONCLUSION: Lower level of mast cells in OSCCs may reflect less need for activation of mast cells in order to increase angiogenesis in OSCCs .Increase in mast cell density in CSCCs suggests a possible role for mast cell in tumor progression of CSCCs.

Factors associated with acute oral mucosal reaction induced by radiotherapy in head and neck squamous cell carcinoma: A retrospective single-center experience.

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Tao, Zhenchao; Gao, Jin; Qian, Liting; Huang, Yifan; Zhou, Yan; Yang, Liping; He, Jian; Yang, Jing; Wang, Ru; Zhang, Yangyang

2017-12-01

To investigate risk factors for acute oral mucosal reaction during head and neck squamous cell carcinoma radiotherapy.A retrospective study of patients with head and neck squamous cell carcinoma who underwent radiotherapy from November 2013 to May 2016 in Anhui Provincial Cancer Hospital was conducted. Data on the occurrence and severity of acute oral mucositis were extracted from clinical records. Based on the Radiation Therapy Oncology Group (RTOG) grading of acute radiation mucosal injury, the patients were assigned into acute reaction (grades 2-4) and minimum reaction (grades 0-1) groups. Preradiotherapy characteristics and treatment factors were compared between the 2 groups. Multivariate logistic regression analysis was used to detect the independent factors associated with acute oral mucosal reactions.Eighty patients completed radiotherapy during the study period. Oral mucosal reactions were recorded as 25, 31, and 24 cases of grades 1, 2, and 3 injuries, respectively. Significant differences between acute reaction and minimum reaction groups were detected in cancer lymph node (N) staging, smoking and diabetes history, pretreatment platelet count and T-Helper/T-Suppressor lymphocyte (Th/Ts) ratio, concurrent chemotherapy, and total and single irradiation doses.Multivariate analysis showed that N stage, smoking history, single dose parapharyngeal irradiation, and pretreatment platelet count were independent risk factors for acute radiation induced oral mucosal reaction. Smoking history, higher grading of N stage, higher single dose irradiation, and lower preirradiation platelet count may increase the risk and severity of acute radiation oral mucosal reaction in radiotherapy of head and neck cancer patients. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Oral cancer

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Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... National Cancer Institute. PDQ lip and oral cavity cancer ... September 25, 2015. www.cancer.gov/types/head-and-neck/hp/lip- ...

Radiation-induced malignant melanoma following radiation treatment for squamous cell carcinoma of the oral cavity - a case report and review of literature -

International Nuclear Information System (INIS)

Shin, Young Ju; Yang, Koang Mo; Suh, Hyun Suk

1998-01-01

Malignant melanoma of the oral cavity is rare, accounting for 1 to 8% of all malignant melanomas. The overall prognosis remains poor despite the available treatments such as radical surgery, adjuvant radiotherapy, chemotherapy and immunotherapy due to failure in early detection and tendency in early metastasis. The etiology of mucosal malignant melanoma remains unkown. However, there are few cases of malignant melanoma of the oral cavity reported in the literature, which might be related to preexisting melanosis and radiation treatment. A case with malignant melanoma developed on the same site after 6 years following irradiation for squamous cell carcinoma of the oral cavity is reported in this article

Evaluation of serum sialic acid, fucose levels and their ratio in oral squamous cell carcinoma.

Science.gov (United States)

Chinnannavar, Sangamesh Ningappa; Ashok, Lingappa; Vidya, Kodige Chandrashekhar; Setty, Sunil Mysore Kantharaja; Narasimha, Guru Eraiah; Garg, Ranjana

2015-01-01

Detection of cancer at the early stage is of utmost importance to decrease the morbidity and mortality of the disease. Apart from the conventional biopsy, minimally invasive methods like serum evaluation are used for screening large populations. Thus, this study aimed to estimate serum levels of sialic acid and fucose and their ratio in oral cancer patients and in healthy control group to evaluate their role in diagnosis. Serum samples were collected from 52 healthy controls (group I) and 52 squamous cell carcinoma patients (group II). Estimation of serum levels of sialic acid and fucose and their ratio was performed. This was correlated histopathologically with the grades of carcinoma. Statistical analysis was done by using analysis of variance (ANOVA) test and unpaired "t" test. Results showed that serum levels of sialic acid and fucose were significantly higher in oral cancer patients compared to normal healthy controls (P ratio was significantly lower in cancer patients than in normal controls (P ratio showed decreasing trend from controls to malignant group. The ratio of sialic acid to fucose can be a useful diagnostic aid for oral cancer patients.

Incidence of Mast Cells in Oral Squamous Cell Carcinoma: A Short Study

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A. Anuradha

2014-01-01

Full Text Available Mast cells are regarded as complex and multifunctional cells, playing a significant role in immunopathology and a substantial role in tumor angiogenesis. Angiogenesis is a complex process that is tightly regulated by various growth factors in which mast cells act directly by releasing angiogenic factors and henceforth promoting tumor growth and metastasis. The aim of this study is to evaluate the number of mast cells in tissue sections of oral squamous cell carcinoma (OSCC in comparison with normal mucosa. A total of 40 cases (20 OSCC and 20 normal mucosa were stained with 1% toluidine blue and the quantitative analysis was done by using light microscope under 400x magnification. A significant increase in the mast cell count was observed in the sections of OSCC when compared to normal mucosa suggesting their contributing role in tumor growth and progression.

Enhanced cell killing and apoptosis of oral squamous cell carcinoma cells with ultrasound in combination with cetuximab coated albumin microbubbles.

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Narihira, Kyoichi; Watanabe, Akiko; Sheng, Hong; Endo, Hitomi; Feril, Loreto B; Irie, Yutaka; Ogawa, Koichi; Moosavi-Nejad, Seyedeh; Kondo, Seiji; Kikuta, Toshihiro; Tachibana, Katsuro

2018-03-01

Targeted microbubbles have the potential to be used for ultrasound (US) therapy and diagnosis of various cancers. In the present study, US was irradiated to oral squamous cell carcinoma cells (HSC-2) in the presence of cetuximab-coated albumin microbubbles (CCAM). Cell killing rate with US treatment at 0.9 W/cm 2 and 1.0 W/cm 2 in the presence of CCAM was greater compared to non-targeted albumin microbubbles (p < .05). On the other hand, selective cell killing was not observed in human myelomonocytic lymphoma cell line (U937) that had no affinity to cetuximab. Furthermore, US irradiation in the presence of CCAM showed a fivefold increase of cell apoptotic rate for HSC-2 cells (21.0 ± 3.8%) as compared to U937 cells (4.0 ± 0.8%). Time-signal intensity curve in a tissue phantom demonstrated clear visualisation of CCAM with conventional US imaging device. Our experiment verifies the hypothesis that CCAM was selective to HSC-2 cells and may be applied as a novel therapeutic/diagnostic microbubble for oral squamous cell carcinoma.

Characterization of dendritic cells in lip and oral cavity squamous cell carcinoma.

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Costa, Nádia Lago; Gonçalves, Andréia Souza; Martins, Allisson Filipe Lopes; Arantes, Diego Antônio Costa; Silva, Tarcília Aparecida; Batista, Aline Carvalho

2016-07-01

There may be differences in the antitumor immunity induced by dendritic cells (DCs) during the development of squamous cell carcinoma (SCC) located in the lip rather than in the oral cavity. The aim of this study was to evaluate the number of immature and mature DCs in SCC and potentially malignant disorders of the oral cavity and lip. Immunohistochemistry was used to identify the number (cells/mm(2) ) of immature (CD1a(+) ) or mature (CD83(+) ) DCs in samples of oral cavity SCC (OCSCC) (n = 39), lip SCC (LSCC) (n = 23), leukoplakia (LK) (n = 21), actinic cheilitis (AC) (n = 13), and normal mucosa of the oral cavity (OC control, n = 12) and the lip (lip control, n = 11). The number of CD1a(+) cells tended to be higher in the OC control samples compared with the LK (P = 0.04) and OCSCC (P = 0.21). Unlike, this cell population was lower in the lip control than in AC or LSCC (P < 0.05). The number of CD83(+) cells was increased in the LSCC samples compared with the AC and lip control (P = 0.0001) and in OCSCC compared with both the LK (P = 0.001) and OC control (P = 0.0001) samples. LSCC showed an elevated number of CD1a(+) and CD83(+) cells compared with OCSCC (P = 0.03). The population of mature DCs was lower than the population of immature DCs in all of the tested groups (P < 0.05). There were a greater number of both mature and immature DC populations in the LSCC samples than in the OCSCC, which could contribute to establishing a more effective immune antitumor response for this neoplasm. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Image findings and bone metabolic markers of bone involvement by oral squamous cell carcinoma

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Kameta, Ayako; Tsuchimochi, Makoto; Harada, Mikiko; Katada, Tsutomu; Sasaki, Yoshihiko; Hayama, Kazuhide

2000-01-01

Recently it has been reported that the circulating pyridinoline cross-linked carboxyl-terminal telopeptide of type I collagen (ICTP) and carboxyl-terminal propeptide of type I procollagen (PICP) are useful markers for detecting metastasis of malignancies to bone. Since ICTP and PICP are related to collagen metabolism, respectively breaking down and synthesizing type I collagen, elevated blood concentrations of these markers may reflect direct jaw bone destruction by oral cancer. The purpose of this study was to clarify the relationship between serum ICTP and PICP levels and bone invasion associated with oral cancer. Bone invasion was evaluated in 41 patients with oral squamous cell carcinoma (SCC) by panoramic radiography and 99m Tc-methylene diphosphonate (MDP) scintigraphy. We also assayed serum levels of parathyroid hormone-related protein (PTHrP) and compared them with concentrations of bone metabolic markers and imaging findings. There was no significant relationship between serum ICTP and PICP levels and bone invasion. However, in three of the five cases that showed remarkably high serum ICTP levels, 99m Tc-MDP uptake in the lesion was intensely increased. This suggests that serum ICTP levels may be elevated when bone metabolic changes caused by cancer involving the bone are extensive. We could find no significant correlation among serum levels of ICTP, PICP, and PTHrP. ICTP and PICP do not appear to be good indicators of direct bone invasion by oral SCC in early stages. (author)

Regular Dental Visits: Influence on Health-Related Quality of Life in 1,607 Patients with Oral Squamous Cell Carcinoma

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Simon Spalthoff

2017-01-01

Full Text Available Background. The incidence of oral squamous cell carcinoma (OSCC is in the top 10 of all cancer entities. Regular oral examinations by dentists play an important role in oral cancer prevention. Methods. Patients with OSCC (n=1,607 and physicians (n=1,489 completed questionnaires during the DÖSAK Rehab Study. The psychosocial and functional factors collected in these questionnaires were assessed in the present study. We compared patients who visited their dentist at least once a year (group A with those who visited their dentist less than once a year (group B. Results. Patients in group A had significantly better health-related quality of life after tumor treatment than patients in group B. Patients in group A also had a smaller tumor size and less lymph node metastasis and lost fewer teeth during the treatment. This resulted in better prosthetic rehabilitation and better psychological status after tumor treatment. Conclusions. Dentists play an important role in the early recognition of oral cancer. This study should encourage dentists to take a more active role in oral cancer prevention.

Low prevalence of human papillomavirus in oral cavity squamous cell carcinoma in Queensland, Australia.

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Emmett, Sarah; Jenkins, Glenn; Boros, Samuel; Whiteman, David C; Panizza, Benedict; Antonsson, Annika

2017-09-01

While human papillomavirus (HPV) is an accepted risk factor for oropharyngeal squamous cell carcinoma (SCC), its aetiological role in oral cavity SCC remains unclear. This study aimed to determine the HPV prevalence in an Australian population. DNA was extracted from 63 formalin-fixed paraffin-embedded tumour specimens histologically confirmed as SCC of the oral cavity, diagnosed during 2006-2012. Clinical data were extracted from medical records. HPV presence was determined by polymerase chain reaction. Positive samples were typed by sequencing. Immunohistochemistry was used to assess p16 INK4A , p53, pRB, Ki67, Cyclin D1 and p21 WAF1 expression. Five of the 63 tumours (8%) were positive for HPV DNA (three HPV-16 positive and two HPV-18 positive). Two tumours overexpressed p16 INK4A (3%) and one of these was also HPV positive. Overexpression of Cyclin D1 correlated significantly with tumour recurrence (P = 0.029) and death (P = 0.002). This study has identified a low prevalence of high-risk HPV in Queensland, Australia. © 2016 Royal Australasian College of Surgeons.

Investigation of the treatment results of advanced squamous cell carcinoma of the oral cavity and clinical necessity of long-term follow-up

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Yamakawa, Nobuhiro; Kirita, Tadaaki; Imai, Yuichiro; Yamanaka, Yasutsugu; Aoki, Kumiko

2011-01-01

It has been considered that oral cancer is cured if more than five years pass without recurrence or metastasis after the initial treatment. Treatment results are usually evaluated as a 5-year survival rate, but we sometimes find recurrence more than five years after the initial treatment. We retrospectively investigated treatment results by long-term follow-up of advanced squamous cell carcinoma of the oral cavity after radical surgery, and analyzed the relation between the period of follow-up and the time to recurrence. One hundred and sixteen patients with advanced squamous cell carcinoma of the oral cavity were enrolled between November 1994 and October 2004 in this study. Seventy-six patients were Stage III and 40 were stage IV, and the mean age of this cohort was 63.0 years. All patients received radical surgery with or without preoperative chemoradiotherapy and were followed for a minimum of 5 years. Overall actuarial survival of all patients was 77.8% at 10 years. The 10-year cumulative local and regional recurrence rates were 20.1% and 12.9%, respectively. The actuarial loco-regional recurrence rate was the highest within 2 years after initial treatment at 19.0%, and was seen in 3.4% even after 5 years. These results showed that it is necessary to follow-up patients with advanced oral cancer even beyond 5 years after the initial treatment because there was delayed loco-regional recurrence in 3.4%. (author)

Comparison between CT and histopathological findings of cervical lymph node metastases in the oral squamous cell carcinoma

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Uchida, Akemi

2001-01-01

The purpose of this study is to clarify the relationship between the findings of contrast-enhanced CT scans and the histopathological findings of regional lymph nodes obtained from a complete extirpation of oral squamous cell carcinoma. Twenty-seven pairs of contrast-enhanced CT scans and histopathological specimens of 27 oral squamous cell carcinoma used in this study were obtained at Kyushu Dental College Hospital between 1987 and 1999. The primary site of the 27 tumor consists of the tongue (13 cases), the mandibular gingiva (6 cases), the maxillary gingiva (4 cases), the floor of the oral cavity (3 cases), and the buccal mucosa (1 case). The results obtained were as follows: Of the 27 cases, 11 (41%) were proven to be positive lymph nodes metastatic cases histopathologically. Metastatic lymph nodes were predominantly detected in both the submandibular regions and the superior internal jugular chains (95%). The length and the ratio of the short and long axes of the metastatic lymph nodes were larger than those of the non-metastatic lymph nodes. Many of the metastatic lymph nodes revealed a low density in their central area and were also accompanied by a thin ring enhancement. Non-metastatic lymph nodes, affected by inflammation, often revealed a heterogeneous density. The ring enhancement was predominantly seen in the metastatic lymph nodes (45%), which were filled with a well-differentiated tumor cell. In the metastatic lymph nodes, which were filled with moderately-differentiated tumor cells, were seen heterogeneous density, but a ring enhancement was not seen. In the metastatic lymph nodes, it was difficult to decide the metastasis by contrast CT scan, if the tumor extension degree was not predominant. The ring enhancement was caused by the dilatation of the capsular vessels, but not by the extra capsular spread of the tumor cells. (author)

Serum Advanced Oxidation Protein Products in Oral Squamous Cell Carcinoma: Possible Markers of Diagnostic Significance

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Abhishek Singh Nayyar

2013-07-01

Full Text Available Background: The aim of this study was to measure the concentrations (levels ofserum total proteins and advanced oxidation protein products as markers of oxidantmediated protein damage in the sera of patients with oral cancers.Methods: The study consisted of the sera analyses of serum total protein andadvanced oxidation protein products’ levels in 30 age and sex matched controls, 60patients with reported pre-cancerous lesions and/or conditions and 60 patients withhistologically proven oral squamous cell carcinoma. One way analyses of variance wereused to test the difference between groups. To determine which of the two groups’ meanswere significantly different, the post-hoc test of Bonferroni was used. The results wereaveraged as mean ± standard deviation. In the above test, P values less than 0.05 weretaken to be statistically significant. The normality of data was checked before thestatistical analysis was performed.Results: The study revealed statistically significant variations in serum levels ofadvanced oxidation protein products (P<0.001. Serum levels of total protein showedextensive variations; therefore the results were largely inconclusive and statisticallyinsignificant.Conclusion: The results emphasize the need for more studies with larger samplesizes to be conducted before a conclusive role can be determined for sera levels of totalprotein and advanced oxidation protein products as markers both for diagnosticsignificance and the transition from the various oral pre-cancerous lesions and conditionsinto frank oral cancers.

The role of epithelial-mesenchymal transition in squamous cell carcinoma of the oral cavity.

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Zidar, Nina; Boštjančič, Emanuela; Malgaj, Marija; Gale, Nina; Dovšak, Tadej; Didanovič, Vojko

2018-02-01

Epithelial-mesenchymal transition (EMT) has emerged as a possible mechanism of cancer metastasizing, but strong evidence for EMT involvement in human cancer is lacking. Our aim was to compare oral spindle cell carcinoma (SpCC) as an example of EMT with oral conventional squamous cell carcinoma (SCC) with and without nodal metastases to test the hypothesis that EMT contributes to metastasizing in oral SCC. Thirty cases of oral SCC with and without nodal metastasis and 15 cases of SpCC were included. Epithelial (cytokeratin, E-cadherin), mesenchymal (vimentin, N-cadherin), and stem cell markers (ALDH-1, CD44, Nanog, Sox-2) and transcription repressors (Snail, Slug, Twist) were analyzed immunohistochemically. We also analyzed the expression of microRNAs miR-141, miR-200 family, miR-205, and miR-429. SpCC exhibited loss of epithelial markers and expression of mesenchymal markers or coexpression of both up-regulation of transcription repressors and down-regulation of the investigated microRNAs. SCC showed only occasional focal expression of mesenchymal markers at the invasive front. No other differences were observed between SCC with and without nodal metastases except for a higher expression of ALDH-1 in SCC with metastases. Our results suggest that SpCC is an example of true EMT but do not support the hypothesis that EMT is involved in metastasizing of conventional SCC. Regarding oral SCC progression and metastasizing, we have been facing a shift from the initial enthusiasm for the EMT concept towards a more critical approach with "EMT-like" and "partial EMT" concepts. The real question, though, is, is there no EMT at all?

The Janus-faced roles of Krüppel-like factor 4 in oral squamous cell carcinoma cells.

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Li, Wenwen; Liu, Man; Su, Ying; Zhou, Xinying; Liu, Yao; Zhang, Xinyan

2015-12-29

Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor that regulates many essential processes, including development and cell differentiation, proliferation, and apoptosis. Along with these roles in normal cells and tissues, KLF4 has important tumor suppressive and oncogenic functions in some malignancies. However, the roles of KLF4 in oral squamous cell carcinoma remain unclear. This study investigated the epigenetic alterations and possible roles of KLF4 in oral cancer carcinogenesis. Notably, KLF4 expression was significantly decreased in human oral cancer tissues compared with healthy controls, and KLF4 promoter hypermethylation contributed to the suppression of KLF4 expression. KLF4 expression was associated with tumor grade. Its expression was much lower in poorly differentiated oral cancers than in well-differentiated cancer cells. KLF4 exerted its antitumor activity in vitro and/or in vivo by inhibiting cell proliferation, cell cycle progression, cell colony formation and by inducing apoptosis. In addition, KLF4 over-expression promoted oral cancer cell migration and invasion in vitro. Knockdown of KLF4 promoted oral cancer cells growth and colony formation, and simultaneously inhibited cell migration and invasion. Mechanistic studies revealed that MMP-9 might contribute to KLF4-mediated cell migration and invasion. These results provide evidence that KLF4 might play Janus-faced roles in oral cancer carcinogenesis, acting both as a tumor suppressor and as an oncogene.

Expression of human telomerase reverse transcriptase protein in oral epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical study

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Raghunandan, Bangalore Nagarajachar; Sanjai, Karpagaselvi; Kumaraswamy, Jayalakshmi; Papaiah, Lokesh; Pandey, Bhavna; Jyothi, Bellur MadhavaRao

2016-01-01

Background: Telomerase is an RNA-dependent DNA polymerase that synthesizes TTAGGG telomeric DNA sequences and almost universally provides the molecular basis for unlimited proliferative potential. The telomeres become shorter with each cycle of replication and reach a critical limit; most cells die or enter stage of replicative senescence. Telomere length maintenance by telomerase is required for all the cells that exhibit limitless replicative potential. It has been postulated that reactivation of telomerase expression is necessary for the continuous proliferation of neoplastic cells to attain immortality. Use of immunohistochemistry (IHC) is a useful, reliable method of localizing the human telomerase reverse transcriptase (hTERT) protein in tissue sections which permits cellular localization. Although there exists a lot of information on telomerase in oral cancer, little is known about their expression in oral epithelial dysplasia and their progression to oral squamous cell carcinoma (OSCC) compared to normal oral mucosa. This study addresses this lacuna. Aims: To compare the expression of hTERT protein in oral epithelial dysplasia and OSCC with normal oral mucosa by Immunohistochemical method. Subjects and Methods: In this preliminary study, IHC was used to detect the expression of hTERT protein in OSCC (n = 20), oral epithelial dysplasia (n = 21) and normal oral mucosa (n = 10). The tissue localization of immunostain, cellular localization of immunostain, nature of stain, intensity of stain, percentage of cells stained with hTERT protein were studied. A total number of 100 cells were counted in each slide. Statistical Analysis: All the data were analyzed using SPSS software version 16.0. The tissue localization, cellular localization of cytoplasmic/nuclear/both of hTERT stain, staining intensity was compared across the groups using Pearson's Chi-square test. The mean percentage of cells stained for oral epithelial dysplasia, OSCC and normal oral mucosa were

Immunolocalization of osteopontin in dysplasias and squamous cell carcinomas arising from oral epithelium.

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Aravind, Thara; Janardhanan, Mahija; Rakesh, S; Savithri, Vindhya; Unnikrishnan, U G

2017-01-01

Early detection of oral squamous cell carcinoma (OSCC) remains one of the most efficient ways to ensure patient survival and improved quality of life. Although specific biomarkers related to OSCC have been investigated, a useful biomarker that assesses the transition potential of potentially malignant lesion to OSCC remains to be found. Osteopontin (OPN) has been recognized as an important factor in tumorigenesis and their expression in OSCC have been investigated earlier. In the present study, evaluation of OPN expression in premalignant and malignant lesions has been carried out to assess their possible role as a biomarker in the early diagnosis and prognosis of OSCC. The objective of this study is to evaluate the role of OPN as a biomarker in the diagnosis and prognosis of OSCC. The study group consisted of archival paraffin-embedded blocks of ten cases each of varying grades of OSCC, oral epithelial dysplasias and epithelial hyperplasias. Sections were subjected to immunohistochemical staining for the biomarker OPN. A positive OPN expression was noticed in epithelial dysplasias and SCC arising from the oral epithelium. A progressive increase in the intensity of staining was seen with increasing grades of dysplasias and a decrease in OPN expression with an increase in grades was observed in OSCC. The expression of OPN in full thickness of epithelium in severe dysplasias, carcinoma in situ, and in the superficial epithelium of OSCC suggest the possibility of considering OPN expression in full epithelial thickness in dysplasias as an indicator for malignant transformation.

NMR (1H and 13C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect

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Bag, Swarnendu; Banerjee, Deb Ranjan; Basak, Amit; Das, Amit Kumar; Pal, Mousumi; Banerjee, Rita; Paul, Ranjan Rashmi; Chatterjee, Jyotirmoy

2015-01-01

At functional levels, besides genes and proteins, changes in metabolome profiles are instructive for a biological system in health and disease including malignancy. It is understood that metabolomic alterations in association with proteomic and transcriptomic aberrations are very fundamental to unravel malignant micro-ambient criticality and oral cancer is no exception. Hence deciphering intricate dimensions of oral cancer metabolism may be contributory both for integrated appreciation of its pathogenesis and to identify any critical but yet unexplored dimension of this malignancy with high mortality rate. Although several methods do exist, NMR provides higher analytical precision in identification of cancer metabolomic signature. Present study explored abnormal signatures in choline metabolism in oral squamous cell carcinoma (OSCC) using 1 H and 13 C NMR analysis of serum. It has demonstrated down-regulation of choline with concomitant up-regulation of its break-down product in the form of trimethylamine N-oxide in OSCC compared to normal counterpart. Further, no significant change in lactate profile in OSCC possibly indicated that well-known Warburg effect was not a prominent phenomenon in such malignancy. Amongst other important metabolites, malonate has shown up-regulation but D-glucose, saturated fatty acids, acetate and threonine did not show any significant change. Analyzing these metabolomic findings present study proposed trimethyl amine N-oxide and malonate as important metabolic signature for oral cancer with no prominent Warburg effect. - Highlights: • NMR ( 1 H and 13 C) study of Oral Squamous cell Carcinoma Serum. • Abnormal Choline metabolomic signatures. • Up-regulation of Trimethylamine N-oxide. • Unchanged lactate profile indicates no prominent Warburg effect. • Proposed alternative glucose metabolism path through up-regulation of malonate

Clinical and Therapeutic Aspects of Squamous Cell Carcinoma of Oral Tongue

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Lee, Chang Gul; Suh, Chang Ok; Kim, Gwi Eon; Loh, John J. K.; Ryu, Samuel; Park, In Kyu

1987-01-01

Forty nine patients with squamous cell carcinoma of oral tongue were reviewed retrospectively for the evaluation of clinical manifestation and for the comparison between therapeutic modalities. The gross shape of the tumor was infiltrative in 22, ulcerative in 12, and ulceroinfiltrative 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 7,000 cGy survived 5 years. This was significant in contrast to 6.4% of the group treated below 7,000 cGy. 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

A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma

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Fan, Song; Tang, Qiong-lan; Lin, Ying-jin; Chen, Wei-liang; Li, Jin-song; Huang, Zhi-quan; Yang, Zhao-hui; Wang, You-yuan; Zhang, Da-ming; Wang, Hui-jing; Dias-Ribeiro, Eduardo; Cai, Qiang; Wang, Lei

2011-01-01

Oral squamous cell carcinoma (OSCC) has a high incidence of cervical micrometastases and sometimes metastasizes contralaterally because of the rich lymphatic intercommunications relative to submucosal plexus of oral cavity that freely communicate across the midline, and it can facilitate the spread of neoplastic cells to any area of the neck consequently. Clinical and histopathologic factors continue to provide predictive information to contralateral neck metastases (CLNM) in OSCC, which determine prophylactic and adjuvant treatments for an individual patient. This review describes the predictive value of clinical-histopathologic factors, which relate to primary tumor and cervical lymph nodes, and surgical dissection and adjuvant treatments. In addition, the indications for elective contralateral neck dissection and adjuvant radiotherapy (aRT) and strategies for follow-up are offered, which is strongly focused by clinicians to prevent later CLNM and poor prognosis subsequently. PMID:22010576

Evaluation of bone scan by scintigraphy to detect subclinical invasion of the mandible by squamous cell carcinoma of the oral cavity

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Baker, H.L.; Woodbury, D.H.; Krause, C.J.; Saxon, K.G.; Stewart, R.C.

1982-01-01

A prospective study using scintigraphy was performed to compare the sensitivity of the Panorex roentgenogram and the bone scan in detecting subclinical invasion of the mandible by squamous cell carcinoma of the oral cavity and floor of the mouth. Twenty-five patients with squamous cell carcinoma of the floor of the mouth were evaluated preoperatively by both the Panorex and scintigraphic techniques and the results compared with postoperative pathologic findings. In 13 (52%) of the cases, Panorex and scintigraphic techniques were comparable in detecting tumor involvement in bone. In eight cases (32%) all three modalities had normal pathologic indications of the mandible. However, in four cases (16%) results of the scintigraphic techniques were abnormal and the Panorex, normal. In four separate cases, the extent of lesion demonstrable by scintiscanning was greater than delineated by Panorex; surgical specimen confirmed this finding. Pathologic examination of operative specimens confirmed tumor involvement. These data lead us to believe that the scintigraphic techniques may be more sensitive in detecting early mandibular involvement with squamous cell carcinoma than the Panorex technique and may help alter the therapeutic approach

Oral manifestations of lupus.

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Menzies, S; O'Shea, F; Galvin, S; Wynne, B

2018-02-01

Mucosal involvement is commonly seen in patients with lupus; however, oral examination is often forgotten. Squamous cell carcinoma arising within oral lupoid plaques has been described, emphasizing the importance of identifying and treating oral lupus. We undertook a retrospective single-centre study looking at oral findings in patients attending our multidisciplinary lupus clinic between January 2015 and April 2016. A total of 42 patients were included. The majority of patients were female (88%) and had a diagnosis of discoid lupus erythematosus (62%). Half of the patients had positive oral findings, 26% had no oral examination documented, and 24% had documented normal oral examinations. Our findings suggest that oral pathology is common in this cohort of patients. Regular oral examination is warranted to identify oral lupus and provide treatment. Associated diseases such as Sjogren's syndrome may also be identified. Patients should be encouraged to see their general dental practitioners on a regular basis for mucosal review. Any persistent ulcer that fails to respond to treatment or hard lump needs urgent histopathological evaluation to exclude malignant transformation to squamous cell carcinoma.

MALDI imaging reveals NCOA7 as a potential biomarker in oral squamous cell carcinoma arising from oral submucous fibrosis.

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Xie, Xiaoyan; Jiang, Yuchen; Yuan, Yao; Wang, Peiqi; Li, Xinyi; Chen, Fangman; Sun, Chongkui; Zhao, Hang; Zeng, Xin; Jiang, Lu; Zhou, Yu; Dan, Hongxia; Feng, Mingye; Liu, Rui; Chen, Qianming

2016-09-13

Oral squamous cell carcinoma (OSCC) ranks among the most common cancer worldwide, and is associated with severe morbidity and high mortality. Oral submucous fibrosis (OSF), characterized by fibrosis of the mucosa of the upper digestive tract, is a pre-malignant lesion, but the molecular mechanisms underlying this malignant transformation remains to be elucidated. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was employed to profile the differentially expressed peptides/proteins between OSCC tissues and the corresponding adjacent non-cancerous OSF tissues. Sixty-five unique peptide peaks and nine proteins were identified with altered expression levels. Of them, expression of NCOA7 was found to be up-regulated in OSCC tissues by immunohistochemistry staining and western blotting, and correlated with a pan of clinicopathologic parameters, including lesion site, tumor differentiation status and lymph node metastasis. Further, we show that overexpression of NCOA7 promotes OSCC cell proliferation in either in vitro or in vivo models. Mechanistic study demonstrates that NCOA7 induces OSCC cell proliferation probably by activating aryl hydrocarbon receptor (AHR). The present study suggests that NCOA7 is a potential biomarker for early diagnosis of OSF malignant transformation, and leads to a better understanding of the molecular mechanisms responsible for OSCC development.

Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma

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Sheng-Dean Luo

2015-01-01

Full Text Available Background. Osteopontin (OPN is a multifunctional cytokine involved in cell survival, migration, and adhesion. However, its role in chemosensitivity in locally advanced oral squamous cell carcinoma (OSCC in humans has not yet been investigated. Methods. We enrolled 121 patients with locally advanced stage IVA/B OSCC receiving cisplatin-based IC followed by CCRT from January 1, 2006, through January 1, 2012. Immunohistochemistry was used to assess OPN expression in OSCC patients’ biopsy specimens from paraffin blocks before treatment. In addition, MTT/colony formation assay was used to estimate the influence of OPN in an oral cancer cell line treated with cisplatin. Results. Of the 121 patients, 94 had positive OPN findings and 52 responded to IC followed by CCRT. Positive osteopontin immunostaining also correlated significantly with positive N status/TNM stage/male gender and smoking. Univariate analyses showed that patients whose tumors had a low expression of OPN were more likely to respond to chemotherapy and have a significantly better OS than those whose tumors had a high expression of OPN. Multivariate analysis revealed that prolonged survival was independently predicted for patients with stage IVA disease, negative lymph nodes, and negative expressions of OPN and for those who received chemotherapy with Docetaxel/cisplatin/fluorouracil (TPF. An oral cancer line stimulated with OPN exhibited a dose-dependent resistance to cisplatin treatment. Conversely, endogenous OPN depletion by OPN-mediated shRNA increased sensitivity to cisplatin. Conclusions. A positive expression of OPN predicts a poor response and survival in patients with locally advanced stage IVA/B OSCC treated with cisplatin-based IC followed by CCRT.

Immunosuppressive mediators of oral squamous cell carcinoma in tumour samples and saliva.

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Gonçalves, Andréia Souza; Arantes, Diego Antonio Costa; Bernardes, Vanessa Fátima; Jaeger, Filipe; Silva, Janine Mayra; Silva, Tarcília Aparecida; Aguiar, Maria Cássia Ferreira; Batista, Aline Carvalho

2015-01-01

The goal of this study was to compare the salivary concentrations of IL-10, TGF-β1 and soluble HLA-G (sHLA-G) in patients with oral squamous cell carcinoma (OSCC) to those in healthy individuals (control group), and to correlate the expression of these mediators in saliva with that in the tumour microenvironment. Neoplastic tissue and saliva samples from patients with OSCC (n=22) were analysed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) respectively. We detected high expression of IL-10 and HLA-G in the tumour microenvironment when compared to healthy oral mucosa samples. Determination of IL-10 salivary concentration enabled us to distinguish patients with OSCC from healthy individuals (P=0.038), which showed correlation with tissue expression of this cytokine. HLA-G salivary release was similar in both groups (P=0.17) and no correlation with tumour expression was observed. TGF-β1 expression was low or absent in tumours, and salivary concentration was similar between groups. Our results suggest that of the three markers analysed, IL-10 is a potential salivary biomarker. Furthermore, the elevated expression of HLA-G and IL-10 in tumour sites could favour the escape of tumour cells from immune defense mechanisms. Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Combined-modality treatment for advanced oral tongue squamous cell carcinoma

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Fan, K.-H.; Lin, C.-Y.; Kang, C.-J.; Huang, S.-F.; Wang, H.-M.; Chen, E.Y.-C.; Chen, I.-H.; Liao, C.-T.; Cheng, A.-J.; Chang, J.T.-C.

2007-01-01

Purpose: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). Methods and Materials: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapy or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8-72.8 Gy). Cisplatin-based regimens were used for chemotherapy. Results: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT = 48.2% vs. without CCRT = 15%, p = 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. Conclusions: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present

Oral cavity squamous cell carcinoma in 260 patients aged 80 years or more

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Ortholan, Cecile; Lusinchi, Antoine; Italiano, Antoine; Bensadoun, Rene-Jean; Auperin, Anne; Poissonnet, Gilles; Bozec, Alexandre; Arriagada, Rodrigo; Temam, Stephane; Benezery, Karen; Thariat, Juliette; Tao Yungan; Janot, Francois; Mamelle, Gerard; Vallicioni, Jacques; Follana, Philippe; Peyrade, Frederic; Sudaka, Anne; Bourhis, Jean; Dassonville, Olivier

2009-01-01

Purpose: We report the experience of two French cancer centers in the treatment of oral cavity squamous cell carcinoma (SCC) in patients aged ≥80 years. Materials and methods: Two hundred and sixty patients aged ≥80 years with a primary oral cavity SCC were included in this retrospective analysis. Results: Sex ratio was near to 1. Tobacco or alcohol intoxication was the main risk factor for 66% of men and 16% of women and leukoplakia, lichen planus, or oral traumatism for 55% of women and 11% of men (p < 0.0001). Two hundred patients received a loco-regional (LR) treatment with a curative intent (surgery and/or radiotherapy), 29 with a palliative intent and 31 did not receive a LR treatment. Curative treatments were initially planned to be adapted to age in 118 patients (59%). The median disease-specific survival (DSS) was 29 months. In multivariate analysis, the independent prognostic factors for DSS were stage (HR = 0.42 [0.24-0.72]), age (HR = 0.43 [0.24-0.75]) and performance status (HR = 0.50 [0.27-0.95]). The median overall survival (OS) was 14 months. In multivariate analysis, the independent prognostic factors for OS were age (HR = 0.52 [0.35-0.79]), stage (HR = 0.56 [0.38-0.84]), tumor differentiation (HR = 0.60 [0.33-0.93]) and performance status (HR = 0.6 [0.37-0.97]). In patients treated with a curative intent, treatment adapted to age was not associated with a decreased overall survival or disease-specific survival as compared with the standard treatment. However, prophylactic lymph node treatment in stages I-II tumors decreased the rate of nodal recurrence from 38% to 6% (p = 0.01). Conclusion: This study emphasizes the need for prospective evaluation of standard and adapted schedules in elderly patients with oral cavity cancer.

Technique, pharmacokinetics, toxicity, and efficacy of intratumoral etanidazole and radiotherapy for treatment of spontaneous feline oral squamous cell carcinoma

International Nuclear Information System (INIS)

Evans, S.M.; LaCreta, F.; Helfand, S.; VanWinkle, T.; Curran, W.J. Jr.; Brown, D.Q.; Hanks, G.

1991-01-01

The histologic appearance, locoregional recurrence, and rate/site of metastases of spontaneous feline oral squamous cell carcinoma are similar to head and neck cancer in humans. A feasibility study of intratumoral Etanidazole, a hypoxic cell sensitizer, and radiation therapy were instituted in this model. Eleven cats with feline squamous cell carcinoma were treated with intratumoral Etanidazole and radiation therapy. Total Etanidazole doses were 1.5-24.0 gms/m2 (0.5-6.9 gms). The tumor partial response rate was 100% (11/11); the median volume regression was 70%. All cats have died as a result of tumor recurrence or tumor-related complications. Median survival was 116 days. Ten cats have been autopsied. Non-necrotic and necrotic tumor cells were identified at the treatment site in all cats. Pharmacokinetic studies were performed in six cats. Following intravenous infusion, the plasma elimination of the Etanidazole was biexponential. The systemic availability following intratumoral administration was 61.2 +/- 21.1%. Peak plasma Etanidazole levels were observed 14 minutes following intratumoral injection, after which elimination was biexponential. Thirty minutes following intratumoral Etanidazole administration, tumor Etanidazole levels were 62.8% of plasma levels. Feline squamous cell carcinoma appears to be a useful model of human head and neck cancer. Cats tolerate substantial doses of intratumoral and intravenous Etanidazole. Etanidazole and radiation therapy cause rapid regression, but not cure, of feline squamous cell carcinoma. There is a similarity between the intravenous kinetics of Etanidazole in humans and cats. Further studies in this model are planned

Expression of Cat Podoplanin in Feline Squamous Cell Carcinomas.

Science.gov (United States)

Itai, Shunsuke; Yamada, Shinji; Kaneko, Mika K; Harada, Hiroyuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

2017-12-01

Oral squamous cell carcinoma is an aggressive tumor in cats; however, molecular-targeted therapies against this tumor, including antibody therapy, have not been developed. Sensitive and specific monoclonal antibodies (mAbs) against highly expressed membrane proteins are needed to develop antibody therapies. Podoplanin, a type I transmembrane glycoprotein, is expressed in many human malignant tumors, including brain tumor, esophageal cancer, lung cancer, mesothelioma, and oral cancer. Podoplanin binds to C-type lectin-like receptor-2 (CLEC-2) and activates platelet aggregation, which is involved in cancer metastasis. Until now, we have established several mAbs against podoplanin in humans, mice, rats, rabbits, dogs, cattle, and cats. We have reported podoplanin expression in canine melanoma and squamous cell carcinomas using an anti-dog podoplanin mAb PMab-38. In this study, we investigated podoplanin expression in 40 feline squamous cell carcinomas (14 cases of mouth floor, 13 of skin, 9 of ear, and 4 of tongue) by immunohistochemical analysis using an anti-cat podoplanin mAb PMab-52, which we recently developed by cell-based immunization and screening (CBIS) method. Of the total 40 cases, 38 (95%) showed positive staining for PMab-52. In particular, 12 cases (30%) showed a strong membrane-staining pattern of squamous cell carcinoma cells. PMab-52 can be useful for antibody therapy against feline podoplanin-expressing squamous cell carcinomas.

Tim-3-expressing macrophages are functionally suppressed and expanded in oral squamous cell carcinoma due to virus-induced Gal-9 expression.

Science.gov (United States)

Dong, Jianfeng; Cheng, Lijun; Zhao, Minchao; Pan, Xiangfeng; Feng, Zhiqiang; Wang, Dawei

2017-05-01

Oropharyngeal head and neck squamous cell carcinoma is a common malignant tumor in the oral cavity. High-risk human papillomavirus 16 infection is a major cause of oropharyngeal head and neck squamous cell carcinoma development. Strong antitumor immune responses, especially CD8 + T cell responses, are thought to be essential to effective cancer treatment and are associated with better prognosis in oropharyngeal head and neck squamous cell carcinoma. In this study, we examined the role of the Tim-3/Gal-9 pathway in oropharyngeal head and neck squamous cell carcinoma patients. We found that Gal-9 expression by CD4 + T cells was increased in human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma patients, but not in human papillomavirus-negative oropharyngeal head and neck squamous cell carcinoma patients. Increased Gal-9 secretion by CD4 + T cells presented multiple immunosuppressive effects. Coculturing monocytes with high Gal-9-expressing CD4 + T cells resulted in the expansion of Tim-3 + monocytes, which suppressed interferon gamma production by activated CD8 + T cells. Subsequently, total monocytes incubated with exogenous Gal-9, or high Gal-9-expressing CD4 + T cells, suppressed the expression of interferon gamma by CD8 + T cells. Exogenous Gal-9 and high Gal-9-expressing CD4 + T cells also suppressed the secretion of both interleukin 10 and interleukin 12 by monocytes. These effects are Tim-3/Gal-9-dependent because blocking Tim-3 and/or Gal-9 could enhance the support of CD8 + T cell interferon gamma production and the interleukin 10 and interleukin 12 secretion by monocytes. Together, these data suggest that the high Tim-3 expression in monocytes could be utilized by tumor-promoting Gal-9 expression on CD4 + T cells. Immunotherapy in human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma patients therefore faces an additional challenge posed by Tim-3 and Gal-9 and likely requires the blockade of these

Oral human papillomavirus infection, sexual behaviors and risk of oral squamous cell carcinoma in southeast of China: A case-control study.

Science.gov (United States)

Chen, Fa; Yan, Lingjun; Liu, Fengqiong; Huang, Jiangfeng; Liu, Fangping; Wu, Junfeng; Qiu, Yu; Zheng, Xiaoyan; Cai, Lin; Lin, Lisong; He, Baochang

2016-12-01

The causal association between human papillomavirus (HPV) and oral squamous cell carcinoma (OSCC) remains controversial. Most of previous studies did not consider the potential modification effect of sexual behaviors when evaluating the role of HPV infection in OSCC risk. To explore the independent and joint effects of oral HPV infection and sexual behaviors on OSCC in Chinese population. A case-control study was conducted from September 2012 to September 2015 in Fujian, China. HPV DNA genotypes were detected in tumor tissues of 178 OSCC patients and oral exfoliated cells of 189 frequency-matched controls using flow-through hybridization and gene chip. Epidemiologic data were collected with a structured questionnaire by face-to-face interviews. Odds ratios (ORs) and 95% confidence interval (CI) were estimated with unconditional logistic regression models. The overall HPV prevalence was 14.04% in OSCC patients and 3.17% in controls. HPV-18 was the most prevalent type in cases and controls (10.67% vs. 2.12%). Oral HPV infection was strongly associated with an increased risk of OSCC: the ORs were 7.21 (95% CI: 2.61-19.88) for HPV16/18 and 7.59 (95% CI: 2.34-24.64) for HPV-18. Moreover, the significant associations were only observed in females, young adults, married population, merchants, non-smokers, non-alcohol drinkers and non-tea drinkers. Additionally, the first intercourse below 22years of age and oral sex practice did not show an association with OSCC. But there was a significantly multiplicative interaction between HPV 16/18 and age at first intercourse for OSCC (P interaction factor for OSCC in Fujian area. Furthermore, there might be a combined effect of HPV 16/18 and age at first intercourse on OSCC. Copyright © 2016 Elsevier B.V. All rights reserved.

Treatment of Squamous Cell Carcinoma of the Oral Cavity, Oropharynx and Hypopharynx

International Nuclear Information System (INIS)

Luukkaa, Marjaana; Minn, Heikki; Aitasalo, Kalle; Kronqvist, Pauliina; Kulmala, Jarmo; Pyrhoenen, Seppo; Grenman, Reidar

2003-01-01

The purpose of this study was to determine the efficacy and feasibility of full-dose preoperative radiation therapy (RT) in head and neck cancer presenting in the oral cavity, oro- and hypopharynx, within a single university hospital district. During a seven-year period, 1989 to 1995, 174 patients with squamous cell carcinoma (SCC) of the oral cavity (OC, 70% of all patients), oropharynx (OP, 15%) and hypopharynx (HP, 15%) were referred to Turku University Central Hospital. All patients were seen by a tumor board consisting of an ENT (ear-nose-throat) head and neck surgeon, a radiation oncologist and a dentist. Potentially curative treatment was given to 142 patients. Of these, 88 (62%) had preoperative RT, 6 (4%) postoperative RT, 34 (24%) definitive RT and 14 patients (10%) were treated with surgery only. The radiation dose was S50 Gy, averagely 64 Gy. The major endpoints of the study were local control, overall survival and major complications of the combined treatment. The 5-year relative survival rate (RSR) was 40% for all, and 43% for patients treated with curative intent. For these, the local control at 5 years was 60%; the disease-specific 5-year survival rate was 65% for the patients with lingual SCC, 45% for those with other oral tumor localizations, 64% for the oropharynx patients and 47% for those with tumor in their hypopharynx, while it was 55% for all patients. The preoperative radiotherapy was fairly well tolerated. Ten (7%) of the patients treated with curative intent suffered major complications, and four patients had evidence of osteoradionecrosis. With the exception of patients with early SCC the outcome remains rather poor in this group of cancer patients who often have marked co-morbidity. In our opinion, preoperative radiotherapy to a dose of 62-64 Gy can safely be given, and remains a feasible means to treat patients with oral, oropharyngeal or hypopharyngeal cancer

Treatment of Squamous Cell Carcinoma of the Oral Cavity, Oropharynx and Hypopharynx

Energy Technology Data Exchange (ETDEWEB)

Luukkaa, Marjaana; Minn, Heikki; Aitasalo, Kalle; Kronqvist, Pauliina; Kulmala, Jarmo; Pyrhoenen, Seppo; Grenman, Reidar [Turku Univ. Central Hospital (Finland). Depts. of Oncology and Radiotherapy

2003-11-01

The purpose of this study was to determine the efficacy and feasibility of full-dose preoperative radiation therapy (RT) in head and neck cancer presenting in the oral cavity, oro- and hypopharynx, within a single university hospital district. During a seven-year period, 1989 to 1995, 174 patients with squamous cell carcinoma (SCC) of the oral cavity (OC, 70% of all patients), oropharynx (OP, 15%) and hypopharynx (HP, 15%) were referred to Turku University Central Hospital. All patients were seen by a tumor board consisting of an ENT (ear-nose-throat) head and neck surgeon, a radiation oncologist and a dentist. Potentially curative treatment was given to 142 patients. Of these, 88 (62%) had preoperative RT, 6 (4%) postoperative RT, 34 (24%) definitive RT and 14 patients (10%) were treated with surgery only. The radiation dose was S50 Gy, averagely 64 Gy. The major endpoints of the study were local control, overall survival and major complications of the combined treatment. The 5-year relative survival rate (RSR) was 40% for all, and 43% for patients treated with curative intent. For these, the local control at 5 years was 60%; the disease-specific 5-year survival rate was 65% for the patients with lingual SCC, 45% for those with other oral tumor localizations, 64% for the oropharynx patients and 47% for those with tumor in their hypopharynx, while it was 55% for all patients. The preoperative radiotherapy was fairly well tolerated. Ten (7%) of the patients treated with curative intent suffered major complications, and four patients had evidence of osteoradionecrosis. With the exception of patients with early SCC the outcome remains rather poor in this group of cancer patients who often have marked co-morbidity. In our opinion, preoperative radiotherapy to a dose of 62-64 Gy can safely be given, and remains a feasible means to treat patients with oral, oropharyngeal or hypopharyngeal cancer.

Function and importance of p63 in normal oral mucosa and squamous cell carcinoma of the head and neck

DEFF Research Database (Denmark)

Thurfjell, Niklas; Coates, Philip J; Boldrup, Linda

2005-01-01

BACKGROUND/AIMS: Squamous cell carcinoma of the head and neck (HNSCC) is the 6th most common malignancy worldwide with a 5-year survival that has not improved over the last 20-25 years. Factors of prognostic significance for this tumour type include the presence of regional lymph node metastasis...... and amplification of chromosome 3q21-29, where the p63 gene is located. This gene encodes 6 proteins and is crucial for formation of the oral mucosa, teeth, salivary glands and skin. Each of the 6 different p63 proteins has different characteristics and functions, where some resemble the tumour suppressor protein p......53, whilst others have functions that oppose p53. METHODS: To understand the function and importance of p63 in oral mucosa and tumour development we have studied protein as well as mRNA expression in normal oral mucosa and tumours. RESULTS/CONCLUSION: Expression of p63 proteins differs between...

Hemimandibulectomy and therapeutic neck dissection with radiotherapy in the treatment of oral squamous cell carcinoma involving mandible: a critical review of treatment protocol in the years 1994-2004

Czech Academy of Sciences Publication Activity Database

Hoffmannová, J.; Foltán, R.; Vlk, M.; Šipoš, M.; Horká, E.; Pavlíková, G.; Kufa, R.; Bulík, O.; Šedý, Jiří

2010-01-01

Roč. 39, č. 6 (2010), s. 561-567 ISSN 0901-5027 Institutional research plan: CEZ:AV0Z50390512 Keywords : squamous cell carcinoma * oral cavity * retrospective study Subject RIV: FH - Neurology Impact factor: 1.302, year: 2010

Sexual behaviour, HPV status and p16INK4a expression in oropharyngeal and oral cavity squamous cell carcinomas: a case-case comparison study.

Science.gov (United States)

Emmett, Sarah; Boros, Samuel; Whiteman, David C; Porceddu, Sandro V; Panizza, Benedict J; Antonsson, Annika

2018-06-01

A significant proportion of mucosal squamous cell carcinomas of the head and neck (HNSCC; particularly of the oropharynx) are directly attributable to the human papillomavirus (HPV). The increase in the incidence of HPV-related tumours has been postulated to be due to changing sexual practices in the community. We analysed 136 formalin-fixed paraffin-embedded squamous cell carcinomas from the oral cavity (n=40) and oropharynx (n=96) recruited from the Princess Alexandra Hospital (Brisbane, Australia). Samples were analysed for the presence of HPV DNA using a combination of mucosal HPV general primer GP+ PCR and sequencing; p 16INK4a expression was assessed by immunohistochemistry. Each patient completed a questionnaire detailing their lifestyle factors, such as tobacco smoking and alcohol consumption, marital status, and sexual behaviour and history. The HPV DNA prevalence was 5 % in the oral cavity cancers and 72 % in the oropharyngeal cancers (P<0.0001). HPV-16 was the most commonly detected HPV type (found in 91 % of all HPV-positive tumours). There was a strong correlation between HPV DNA positivity and positive p16 INK4a staining in oropharyngeal tumours (P<0.0001). Having an HPV-related tumour was associated with being married or having been married previously (P=0.046), an increasing number of passionate kissing partners (P=0.046), ever having given oral sex (P=0.0007) and an increasing number of oral sex partners (P=0.0015). This study found a higher prevalence of HPV in oropharyngeal compared to oral cavity tumours, with a strong association being identified between oral sex behaviours and HPV-positive tumours. Further research is needed to establish that vaccines will reduce the transmission and carriage of oropharyngeal HPV infections.

Human papilloma virus 18 detection in oral squamous cell carcinoma and potentially malignant lesions using saliva samples.

Science.gov (United States)

Goot-Heah, Khor; Kwai-Lin, Thong; Froemming, Gabriele Ruth Anisah; Abraham, Mannil Thomas; Nik Mohd Rosdy, Nik Mohd Mazuan; Zain, Rosnah Binti

2012-01-01

Oral cancer has become one of the most prevalent cancers worldwide and human Papillomavirus is one of the risk factors for developing oral cancer. For this study HPV18 was chosen as it is one of the high risk HPV types and may lead to carcinogenesis. However, prevalence of HPV18 infection in Oral Squamous Cell Carcinoma in Malaysia remains unclear. This study aimed to investigate the viral load of HPV18 DNA in OSCC and potentially malignant lesions using saliva samples. Genomic DNAs of thirty saliva samples of normal subjects and thirty saliva samples compromised of 16 samples from potentially malignant lesions and 14 of OSCC patients were amplified for HPV18 DNA using a nested polymerase chain reaction analysis. All PCR products were then analyzed using the Bioanalyzer to confirm presence of HPV18 DNA. From thirty patients examined, only one of 30 (3.3%) cases was found to be positive for HPV18 in this study. The finding of this study revealed that there is a low viral detection of HPV18 in Malaysian OSCC by using saliva samples, suggesting that prevalence of HPV18 may not be important in this group of Malaysian OSCC.

Prognostic utility of chromosomal instability detected by fluorescence in situ hybridization in fine-needle aspirates from oral squamous cell carcinomas

International Nuclear Information System (INIS)

Sato, Hiroaki; Uzawa, Narikazu; Takahashi, Ken-Ichiro; Myo, Kunihiro; Ohyama, Yoshio; Amagasa, Teruo

2010-01-01

Although chromosomal instability (CIN) has been detected in many kinds of human malignancies by means of various methods, there is no practical assessment for small clinical specimens. In this study, we evaluated CIN in fine-needle aspiration (FNA) biopsied oral squamous cell carcinomas (SCCs) using fluorescence in situ hybridization (FISH) analysis, and investigated its prognostic significance. To evaluate CIN status of tumors, FISH with genomic probes for the centromeres of chromosomes 7, 9, and 11 was performed on specimens obtained by FNA from 77 patients with primary oral SCCs. High-grade CIN (CIN3) was observed in 11.7% (9/77) of patients with oral SCCs and was associated significantly with reduced disease-free survival (p = .008) and overall survival (p = .003). Multivariate Cox proportional hazards analysis showed that CIN status was significantly correlated with disease-free survival (p = .035) and overall survival (p = .041). Analysis of CIN status using FISH on FNA biopsy specimens may be useful in predicting of recurrence and poor prognosis in patients with oral SCCs

Parathyroid hormone-related protein (PTHrP) expression and bone invasion by oral squamous cell carcinoma

International Nuclear Information System (INIS)

Tsuchimochi, Makoto; Kameta, Ayako; Harada, Mikiko; Okada, Yasuo; Katagiri, Masataka

1999-01-01

Parathyroid hormone-related protein (PTHrP) indirectly stimulates osteoclastic bone resorption through osteoblasts in humoral hypercalcemia of malignancy. We reported that the serum concentration of PTHrP elevated in terminal stage patients with oral squamous cell carcinoma (SCC) in 1996. Therefore, PTHrP is a candidate for direct bone resorption factor released from the tumor tissue. The purpose of this study was to elucidate the correlation between the direct bone invasion by oral SCC and PTHrP expression. The serum C-PTHrP concentration was measured in 53 patients with oral SCC. The immunohistochemical study using PTHrP (labeled streptoavidin-biotin method, 38-64 monoclonal and 1-34 polyclonal antibody) was performed in 53 biopsy specimens. The bone invasion was assessed by using panoramic radiographs and bone scintigrams ( 99m Tc-MDP). The mean serum C-PTHrP concentration in the bone invasion identified group was 43.1±17.2 pmol/1. In the non-bone invasion group it was 42.0±18.0 pmol/1. No significant correlation was found between serum C-PTHrP levels and bone invasion or between PTHrP (1-34) and (38-64) expression in tumors and bone invasion. These results showed that there is no relationship between PTHrP expression in the biopsy specimen and direct bone invasion. Since the expression of PTHrP in the tumor tissue attached to the bone or surgical specimens has not been investigated, it is still unclear if PTHrP plays a role in direct bone resorption by oral SCC. (author)

NMR ({sup 1}H and {sup 13}C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect

Energy Technology Data Exchange (ETDEWEB)

Bag, Swarnendu, E-mail: Swarna.bag@gmail.com [School of Medical Science and Technology, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Banerjee, Deb Ranjan, E-mail: debranjan2@gmail.com [Department of Chemistry, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Basak, Amit, E-mail: absk@chem.iitkgp.ernet.in [Department of Chemistry, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Das, Amit Kumar, E-mail: amitk@hijli.iitkgp.ernet.in [Department of Biotechnology, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Pal, Mousumi, E-mail: drmpal62@gmail.com [Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Kolkata, West Bengal (India); Banerjee, Rita, E-mail: ritabanerjee@outlook.com [Department of Science and Technology, New Mehrauli Road, New Delhi 110016 (India); Paul, Ranjan Rashmi, E-mail: dr_rsspaul@yahoo.co.in [Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Kolkata, West Bengal (India); Chatterjee, Jyotirmoy, E-mail: jchatterjee.iitkgp@gmail.com [School of Medical Science and Technology, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India)

2015-04-17

At functional levels, besides genes and proteins, changes in metabolome profiles are instructive for a biological system in health and disease including malignancy. It is understood that metabolomic alterations in association with proteomic and transcriptomic aberrations are very fundamental to unravel malignant micro-ambient criticality and oral cancer is no exception. Hence deciphering intricate dimensions of oral cancer metabolism may be contributory both for integrated appreciation of its pathogenesis and to identify any critical but yet unexplored dimension of this malignancy with high mortality rate. Although several methods do exist, NMR provides higher analytical precision in identification of cancer metabolomic signature. Present study explored abnormal signatures in choline metabolism in oral squamous cell carcinoma (OSCC) using {sup 1}H and {sup 13}C NMR analysis of serum. It has demonstrated down-regulation of choline with concomitant up-regulation of its break-down product in the form of trimethylamine N-oxide in OSCC compared to normal counterpart. Further, no significant change in lactate profile in OSCC possibly indicated that well-known Warburg effect was not a prominent phenomenon in such malignancy. Amongst other important metabolites, malonate has shown up-regulation but D-glucose, saturated fatty acids, acetate and threonine did not show any significant change. Analyzing these metabolomic findings present study proposed trimethyl amine N-oxide and malonate as important metabolic signature for oral cancer with no prominent Warburg effect. - Highlights: • NMR ({sup 1}H and {sup 13}C) study of Oral Squamous cell Carcinoma Serum. • Abnormal Choline metabolomic signatures. • Up-regulation of Trimethylamine N-oxide. • Unchanged lactate profile indicates no prominent Warburg effect. • Proposed alternative glucose metabolism path through up-regulation of malonate.

Cantharidin Induced Oral Squamous Cell Carcinoma Cell Apoptosis via the JNK-Regulated Mitochondria and Endoplasmic Reticulum Stress-Related Signaling Pathways.

Directory of Open Access Journals (Sweden)

Chin-Chuan Su

Full Text Available Oral cancer is a subtype of head and neck cancer which represents 2.65% of all human malignancies. Most of oral cancer is histopathologically diagnosed as oral squamous cell carcinoma (OSCC. OSCC is characterized by a high degree of local invasion and a high rate of metastasis to the cervical lymph nodes. How to prevention and treatment of OSCC is important and imperative. Here, we investigated the therapeutic effect and molecular mechanism of cantharidin, an active compound isolated from blister beetles, on OSCC in vitro. Results showed that cantharidin significantly decreased cell viability in human tongue squamous carcinoma-derived SAS, CAL-27, and SCC-4 cell lines. The further mechanistic studies were carried out in SAS cells. Cantharidin also significantly increased apoptosis-related signals, including caspase-9, caspase-7 and caspase-3 proteins. Besides, cantharidin decreased mitochondrial transmembrane potential (MMP and induced cytochrome c and apoptosis inducing factor (AIF release. Cantharidin also increased Bax, Bid, and Bak protein expressions and decreased Bcl-2 protein expression. Cantharidin could also increase the endoplasmic reticulum (ER stress signals, including the expressions of phosphorylated eIF-2α and CHOP, but not Grp78 and Grp94. Furthermore, cantharidin reduced pro-caspase-12 protein expression. In signals of mitogen-activated protein kinases, cantharidin increased the phosphorylation of JNK, but not ERK and p38. Transfection of shRNA-JNK to OSCC cells effectively reversed the cantharidin-induced cell apoptotic signals, including the mitochondrial and ER stress-related signaling molecules. Taken together, these findings suggest that cantharidin induces apoptosis in OSCC cells via the JNK-regulated mitochondria and ER stress-related signaling pathways.

Establishment and Characterization of Primary Cultures from Iranian Oral Squamous Cell Carcinoma Patients by Enzymatic Method and Explant Culture

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Meysam Ganjibakhsh

2017-10-01

Full Text Available Objectives: Oral Squamous Cell Carcinoma (OSCC is the most frequent oral cancer worldwide. It is known as the eighth most common cancer in men and as the fifth most common cancer in women. Cytogenetic and biochemical studies in recent decades have emphasized the necessity of providing an appropriate tool for such researches. Cancer cell culture is a useful tool for investigations on biochemical, genetic, molecular and immunological characteristics of different cancers, including oral cancer. Here, we explain the establishment process of five primary oral cancer cells derived from an Iranian population.Materials and Methods: The specimens were obtained from five oral cancer patients. Enzymatic, explant culture and magnetic-activated cell sorting (MACS methods were used for cell isolation. After quality control tests, characterization and authentication of primary oral cancer cells were performed by short tandem repeats (STR profiling, chromosome analysis, species identification, and monitoring the growth, morphology and the expression of CD326 and CD133 markers.Results: Five primary oral cancer cells were established from an Iranian population. The flow cytometry results showed that the isolated cells were positive for CD326 and CD133 markers. Furthermore, the cells were free from mycoplasma, bacterial and fungal contamination. No misidentified or cross-contaminated cells were detected by STR analysis.Conclusions: Human primary oral cancer cells provide an extremely useful platform for studying carcinogenesis pathways of oral cancer in Iranian population. They may be helpful in explaining the ethnic differences in cancer biology and the individuality in anticancer drug response in future studies.

Nrf2 regulates cellular behaviors and Notch signaling in oral squamous cell carcinoma cells.

Science.gov (United States)

Fan, Hong; Paiboonrungruan, Chorlada; Zhang, Xinyan; Prigge, Justin R; Schmidt, Edward E; Sun, Zheng; Chen, Xiaoxin

2017-11-04

Oxidative stress is known to play a pivotal role in the development of oral squamous cell carcinoma (OSCC). We have demonstrated that activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway has chemopreventive effects against oxidative stress-associated OSCC. However, Nrf2 have dual roles in cancer development; while it prevents carcinogenesis of normal cells, hyperactive Nrf2 also promotes the survival of cancer cells. This study is aimed to understand the function of Nrf2 in regulating cellular behaviors of OSCC cells, and the potential mechanisms through which Nrf2 facilitates OSCC. We established the Nrf2-overexpressing and Nrf2-knockdown OSCC cell lines, and examined the function of Nrf2 in regulating cell proliferation, migration, invasion, cell cycle and colony formation. Our data showed that Nrf2 overexpression promoted cancer phenotypes in OSCC cells, whereas Nrf2 silencing inhibited these phenotypes. In addition, Nrf2 positively regulated Notch signaling pathway in OSCC cells in vitro. Consistent with this observation, Nrf2 activation in Keap1 -/- mice resulted in not only hyperproliferation of squamous epithelial cells in mouse tongue as evidenced by increased expression of PCNA, but also activation of Notch signaling in these cells as evidenced by increased expression of NICD1 and Hes1. In conclusion, Nrf2 regulates cancer behaviors and Notch signaling in OSCC cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Expression of cancer-testis antigens MAGE-A4 and MAGE-C1 in oral squamous cell carcinoma.

Science.gov (United States)

Montoro, José Raphael de Moura Campos; Mamede, Rui Celso Martins; Neder Serafini, Luciano; Saggioro, Fabiano Pinto; Figueiredo, David Livingstone Alves; Silva, Wilson Araújo da; Jungbluth, Achim A; Spagnoli, Giulio Cesare; Zago, Marco Antônio

2012-08-01

Tumor markers are genes or their products expressed exclusively or preferentially in tumor cells and cancer-testis antigens (CTAs) form a group of genes with a typical expression pattern expressed in a variety of malignant neoplasms. CTAs are considered potential targets for cancer vaccines. It is possible that the CTA MAGE-A4 (melanoma antigen) and MAGE-C1 are expressed in carcinoma of the oral cavity and are related with survival. This study involved immunohistochemical analysis of 23 patients with oral squamous cell carcinoma (SCC) and was carried out using antibodies for MAGE-A4 and MAGE-C1. Fisher's exact test and log-rank test were used to evaluate the results. The expression of the MAGE-A4 and MAGE-C1 were 56.5% and 47.8% without statistical difference in studied variables and survival. The expression of at least 1 CTA was present in 78.3% of the patients, however, without correlation with clinicopathologic variables and survival. Copyright © 2011 Wiley Periodicals, Inc.

Human Calmodulin-Like Protein CALML3: A Novel Marker for Normal Oral Squamous Mucosa That Is Downregulated in Malignant Transformation

Directory of Open Access Journals (Sweden)

Michael D. Brooks

2013-01-01

Full Text Available Oral cancer is often diagnosed only at advanced stages due to a lack of reliable disease markers. The purpose of this study was to determine if the epithelial-specific human calmodulin-like protein (CALML3 could be used as marker for the various phases of oral tumor progression. Immunohistochemical analysis using an affinity-purified CALML3 antibody was performed on biopsy-confirmed oral tissue samples representing these phases. A total of 90 tissue specimens were derived from 52 patients. Each specimen was analyzed in the superficial and basal mucosal cell layers for overall staining and staining of cellular subcompartments. CALML3 was strongly expressed in benign oral mucosal cells with downregulation of expression as squamous cells progress to invasive carcinoma. Based on the Cochran-Armitage test for trend, expression in the nucleus and at the cytoplasmic membrane significantly decreased with increasing disease severity. Chi-square test showed that benign tissue specimens had significantly more expression compared to dysplasia/CIS and invasive specimens. Dysplasia/CIS tissue had significantly more expression than invasive tissue. We conclude that CALML3 is expressed in benign oral mucosal cells with a statistically significant trend in downregulation as tumorigenesis occurs. CALML3 may thus be a sensitive new marker for oral cancer screening.

Computed tomographic appearance of the recurrent patterns of the oropharyngeal and oral cavity squamous cell carcinomas

International Nuclear Information System (INIS)

Sasaki, Fumio; Kido, Choichiro

1988-01-01

The parapharyngeal invasion were seen often in the case of the squamous cell carcinoma between oropharynx and oral cavity. The recurrent cases with preoperative parapharyngeal invasion have a tendency to invade skull base via parapharyngeal and retropharyngeal space. The recurrent cases without preoperative parapharyngeal invasion have no such a tendency. The fashion of invasion were down-ward, namely inferior parapharyngeal invasion. The recurrent cases of postoperative tongue cancer had one more fashion of deep muscular invasion, ie suprahyoid intramuscular invasion that showed extension from tongue base to suprahyoid region. CT scanning were useful not only for the pre-operative evaluation of parapharyngeal invasion but also for the assessmen of the post operative prognosis. (author)

CD163+ Tumor-Associated Macrophages Correlated with Poor Prognosis and Cancer Stem Cells in Oral Squamous Cell Carcinoma

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Ke-Fei He

2014-01-01

Full Text Available Tumor-associated macrophages (TAMs play an important role in the progression and prognostication of numerous cancers. However, the role and clinical significance of TAM markers in oral squamous cell carcinoma (OSCC has not been elucidated. The present study was designed to investigate the correlation between the expression of TAM markers and pathological features in OSCC by tissue microarray. Tissue microarrays containing 16 normal oral mucosa, 6 oral epithelial dysplasia, and 43 OSCC specimens were studied by immunohistochemistry. We observed that the protein expression of the TAM markers CD68 and CD163 as well as the cancer stem cell (CSC markers ALDH1, CD44, and SOX2 increased successively from the normal oral mucosa to OSCC. The expressions of CD68 and CD163 were significantly associated with lymph node status, and SOX2 was significantly correlated with pathological grade and lymph node status, whereas ALDH1 was correlated with tumor stage. Furthermore, CD68 was significantly correlated with CD163, SOX2, and ALDH1 (P<0.05. Kaplan-Meier analysis revealed that OSCC patients overexpressing CD163 had significantly worse overall survival (P<0.05. TAM markers are associated with cancer stem cell marker and OSCC overall survival, suggesting their potential prognostic value in OSCC.

Human papilloma virus 16/18: Fabricator of trouble in oral squamous cell carcinoma.

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Zil-E-Rubab; Baig, Saeeda; Zaman, Uzma; Lucky, Mohammad Haris

2018-04-01

To find out the association between Human Papilloma Virus (HPV) genotypes 16/18 in Pakistani patients with oral squamous cell carcinoma (OSCC). DNA from oral rinse of 300 subjects was taken. The subjects included 100 cases with OSCC and 200 controls. Samples were analyzed by both conventional and real time PCR using "HPV consensus Gp5+/Gp6+ and HPV 16, 18 specific primers". Out of 300 persons, 74/300 (25%) were found to be infected with HPV: "46/100(46%) from cases and 74/200(14%) from controls". The distribution was: HPV16, 6/300 (8%): 4/100 (9%) from OSCC group and 2/200 (8%) from controls while HPV 18 was 9/300(12%): 5/100(11%) from cases and 4/200(16%) from controls. Out of 300 subjects, 26(35%) were infected by "both HPV 16/18 (23(50%) from cases and 3(12%) from controls". Persons who were infected with HPV 16&18 had higher chances to develop OSCC as compared to those who didn't have HPV 16/18 (AOR: 21.4, 95% CI: 5.73 - 80.8). The exposure to high risk strains of Human papilloma virus (16/18) in combination can be fabricotor of trouble (p<0.001, Adjusted odds ratio; 21.42) in OSCC. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients

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Snitcovsky Igor

2010-05-01

Full Text Available Abstract Background To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC. Patients and Methods We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 oropharynx and 4 hypopharynx SCC and 65 matched adjacent mucosa, available for study, were also included. For survival analysis, patients were categorized as positive or negative for each Smad, according to median mRNA expression. We also performed real-time quantitative PCR (QRTPCR to asses the pattern of TGFβ1, TGFβ2, TGFβ3 in oral SCC. Results Our results showed that Smad2 and Smad6 mRNA expression were both associated with survival in Oral SCC patients. Cox Multivariate analysis revealed that Smad6 positivity and Smad2 negativity were both predictive of good prognosis for oral SCC patients, independent of lymph nodal status (P = 0.003 and P = 0.029, respectively. In addition, simultaneously Smad2- and Smad6+ oral SCC group of patients did not reach median overall survival (mOS whereas the mOS of Smad2+/Smad6- subgroup was 11.6 months (P = 0.004, univariate analysis. Regarding to TGFβ isoforms, we found that Smad2 mRNA and TGFβ1 mRNA were inversely correlated (p = 0.05, R = -0.33, and that seven of the eight TGFβ1+ patients were Smad2-. In larynx SCC, Smad7- patients did not reach mOS whereas mOS of Smad7+ patients were only 7.0 months (P = 0.04. No other correlations were found among Smad expression, clinico-pathological characteristics and survival in oral, larynx, hypopharynx, oropharynx or the entire head and neck SCC population. Conclusion Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection. The underlying mechanism which involves aberrant TGFβ signaling should be better clarified in the future.

Upregulated Expression of Transient Receptor Potential Cation Channel Subfamily V Receptors in Mucosae of Patients with Oral Squamous Cell Carcinoma and Patients with a History of Alcohol Consumption or Smoking.

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Sakakibara, Akiko; Sakakibara, Shunsuke; Kusumoto, Junya; Takeda, Daisuke; Hasegawa, Takumi; Akashi, Masaya; Minamikawa, Tsutomu; Hashikawa, Kazunobu; Terashi, Hiroto; Komori, Takahide

2017-01-01

Transient receptor potential cation channel (subfamily V, members 1-4) (TRPV1-4) are expressed in skin and neurons and activated by external stimuli in normal mucosae of all oral cavity sites. The oral cavity is exposed to various stimuli, including temperature, mechanical stimuli, chemical substances, and changes in pH, and, notably, the risk factors for oncogenic transformation in oral squamous epithelium are the same as the external stimuli received by TRPV1-4 receptors. Hence, we examined the relationship between oral squamous cell carcinoma (SCC) and TRPV1-4 expression. Oral SCC patients (n = 37) who underwent surgical resection were included in this study. We investigated the expression of TRPV1-4 by immunohistochemical staining and quantification of TRPV1-4 mRNA in human oral mucosa. In addition, we compared the TRPV1-4 levels in mucosa from patients with SCC to those in normal oral mucosa. The receptors were expressed in oral mucosa at all sites (tongue, buccal mucosa, gingiva, and oral floor) and the expression was stronger in epithelia from patients with SCC than in normal epithelia. Furthermore, alcohol consumption and tobacco use were strongly associated with the occurrence of oral cancer and were found to have a remarkable influence on TRPV1-4 receptor expression in normal oral mucosa. In particular, patients with a history of alcohol consumption demonstrated significantly higher expression levels. Various external stimuli may influence the behavior of cancer cells. Overexpression of TRPV1-4 is likely to be a factor in enhanced sensitivity to external stimuli. These findings could contribute to the establishment of novel strategies for cancer therapy or prevention.

The Number of Pathologically Positive Lymph Nodes and Pathological Tumor Depth Predicts Prognosis in Patients With Poorly Differentiated Squamous Cell Carcinoma of the Oral Cavity

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Kang, Chung-Jan; Lin, Chien-Yu; Wang, Hung-Ming; Fan, Kang-Hsing; Ng, Shu-Hang; Lee, Li-Yu; Chen, I-How; Huang, Shiang-Fu

2011-01-01

Purpose: The objective of this retrospective study was twofold: (1) to investigate prognostic factors for clinical outcomes in patients with poorly differentiated oral cavity squamous cell carcinoma and (2) to identify specific prognostic subgroups that may help to guide treatment decisions. Methods and Materials: We examined 102 patients with poorly differentiated oral cavity squamous cell carcinoma. All patients were followed for at least 24 months after surgery or until death. The 5-year rates of local control, neck control, distant metastasis, disease-free, disease-specific, and overall survival served as main outcome measures. Results: The 5-year rates were as follows: local control (79%), neck control (64%), distant metastases (27%), disease-free survival (48%), disease-specific survival (52%), and overall survival (42%). Multivariable analysis showed that the number of pathologically positive nodes (≥4 vs. ≤3) was a significant predictor of neck control, distant metastasis, and disease-free, disease-specific, and overall survival rates. In addition, the presence of tumor depth of ≥11 mm (vs. <11 mm) was a significant predictor of distant metastasis, disease-specific survival, and overall survival rates. The combination of the two predictors (26.5%, 27/102) was independently associated with poorer neck control (p = 0.0319), distant metastasis (p < 0.0001), and disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p < 0.0001) rates. Conclusions: In patients with poorly differentiated oral cavity squamous cell carcinoma, the presence of at least 4 pathologically positive lymph nodes and of a pathological tumor depth ≥11 mm identifies a subset of subjects with poor clinical outcomes. Patients carrying both risk factors are suitable candidates for the development of novel therapeutic approaches.

Evaluation of cytomorphometric changes in tobacco users and diagnosed oral squamous cell carcinoma individuals

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Urmila Udayashankar

2016-01-01

Full Text Available Aims: To determine the cellular and nuclear area of keratinocytes in smears obtained from the oral mucosa of tobacco users, those with oral squamous cell carcinoma (OSCC, and from normal healthy persons and resolve if any significant difference exists in these three groups. Materials and Methods: The study group comprised 100 subjects 20 controls, (40 OSCC patients-20 from lesional sites and 20 from nonlesional sites, 20 tobacco smokers and 20 tobacco chewers in the age group of 25-75 years. Oral mucosal smears obtained by using a cytobrush were stained with Papanicolaou (PAP stain and using 20X objective in trinocular Olympus model BX53 with Jenoptik scientific grade-dedicated microphotographic camera images were taken. With ProgRes version 8.0 image analysis software, 20 cells with defined borders were evaluated from each slide. Finally, one-way analysis of variance (ANOVA was used to compare the above parameters in the studied groups. Statistical Analysis Used: Minitab and Excel software were used to analyze the data. One-way ANOVA was used to compare the above parameters in the studied groups. Results: The mean value of the cell area for groups I, II, III, IV, and V were 2838 ± 275.2, 2762.1 ± 511.4, 2861.9 ± 512.9, 2643.8 ± 333.3, and 3064.3 ± 362.7, respectively, the nuclear area (NA was 83.88 ± 9.86, 106.19 ± 13.45, 95.11 ± 14.24, 85.55 ± 21.11, and 80.83 ± 13.45, respectively, and nuclear-to-cellular (N:C ratio was 0.0297, 0.03924, 0.0337, 0.03257, and 0.02678, respectively. Conclusions: Thus, our study elucidates that cytomorphology gauges the effect of tobacco on the oral mucosa and possibly establishes a link between premalignant and malignant transformations even before a lesion is visibly noted.

Significance of post-resection tissue shrinkage on surgical margins of oral squamous cell carcinoma.

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El-Fol, Hossam Abdelkader; Noman, Samer Abduljabar; Beheiri, Mohamed Galal; Khalil, Abdalla M; Kamel, Mahmoud Mohamed

2015-05-01

Resecting oral squamous cell carcinoma (SCC) with an appropriate margin of uninvolved tissue is critical in preventing local recurrence and in making decisions regarding postoperative radiation therapy. This task can be difficult due to the discrepancy between margins measured intraoperatively and those measured microscopically by the pathologist after specimen processing. A total of 61 patients underwent resective surgery with curative intent for primary oral SCC were included in this study. All patients underwent resection of the tumor with a measured 1-cm margin. Specimens were then submitted for processing and reviewing, and histopathologic margins were measured. The closest histopathologic margin was compared with the in situ margin (1 cm) to determine the percentage discrepancy. The mean discrepancy between the in situ margins and the histopathological margins of all close and positive margins were 47.6% for the buccal mucosa (with a P value corresponding to 0.05 equaling 2.1), which is statistically significant, 4.8% for the floor of mouth, 9.5% for the mandibular alveolus, 4.8% for the retromolar trigon, and 33.3% for the tongue. There is a significant difference among resection margins based on tumor anatomical location. Margins shrinkage after resection and processing should be considered at the time of the initial resection. Tumors located in the buccal mucosa show significantly greater discrepancies than tumors at other sites. These findings suggest that it is critical to consider the oral site when outlining margins to ensure adequacy of resection. Buccal SCC is an aggressive disease, and should be considered as an aggressive subsite within the oral cavity, requiring a radical and aggressive resective approach. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Experimental immunotargeting therapy for esophageal squamous cell carcinoma using anti-human esophageal monoclonal antibody KIS1

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Fujii, Teruhiko; Yamana, Hideaki; Higaki, Kensaku; Fujita, Hiromasa; Shirouzu, Kazuo; Morimatsu, Minoru

1997-01-01

In recent years, several MoAbs with high specificity to tumor associated antigens, have been produced and investigated for diagnosis and immunotherapy of tumors. We produced murine MoAb KIS1 against human squamous cell carcinoma of the esophagus, and we evaluated it and its F (ab') 2 fragment for experimental radioimmunotherapy (RIT), RIT combined with hyperthermia (HT) and KIS1-vindesine (VDS) conjugate using tumor bearing nude mice. KIS1 has been shown to react specifically with an antigen of human squamous cell carcinoma. Scintigraphy produced high quality tumor images on 3 days following the injection of 131 I-KIS1F (ab') 2 . By 14 days following injection, tumor bearing mice treated with RIT+HT group showed significant tumor growth inhibition about 1.5, 2.1 and 1.7 times greater than that of the KIS1-VDS group, 131 I-intact KIS1 group and 131 I-KIS1F (ab') 2 group. These results suggest that RIT combined with hyperthermia may be clinically useful for tumor targeting therapy for squamous cell carcinoma of the esophagus. (author)

Src Family Kinases Mediate Betel Quid-Induced Oral Cancer Cell Motility and Could Be a Biomarker for Early Invasion in Oral Squamous Cell Carcinoma

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Jeff Yi-Fu Chen

2008-12-01

Full Text Available Betel quid (BQ-chewing oral cancer is a prevalent disease in many countries of Southeast Asia. Yet, the precise disease mechanism remains largely unknown. Here, we show that BQ extract-induced cell motility in three oral cancer cells (Ca9-22, SAS, and SCC9 presumably involves the Src family kinases (SFKs. Besides, BQ extract can markedly induce cell migration of wild type mouse embryonic fibroblasts (MEFs but not MEFs lacking three SFK members, namely, Src, Yes, and Fyn, indicating the requirement of SFKs for BQ-induced cell motility. Betel quid extract can also elevate cellular SFK activities because phosphorylation of tyrosine 416 at the catalytic domain is increased, which in turn promotes phosphorylation of an in vitro substrate, enolase. Furthermore, we identified that areca nut, a major component of BQ, is the key factor accounting for BQ-induced cell migration and invasion through SFKs-mediated signaling pathways. Immunohistochemistry revealed that, particularly in BQ-chewing cases, the activity of SFKs was significantly higher in tumor-adjacent mucosa than that in solid tumor areas (P < .01. These results suggest a possible role of SFKs in tumor-host interface and thus in early tumor invasion in vivo. Consistent with this is the observation that activation of SFKs is colocalized with invasive tumor fronts in oral squamous cell carcinoma. Together, we conclude that SFKs may represent a potential biomarker of invasion and therapeutic target in BQ-induced oral cancer.

AZD2014 Radiosensitizes Oral Squamous Cell Carcinoma by Inhibiting AKT/mTOR Axis and Inducing G1/G2/M Cell Cycle Arrest.

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Chih-Chia Yu

Full Text Available Oral squamous cell carcinoma (OSCC is one of the most common malignant neoplasms in Taiwan. Activation of the mTOR signaling pathway has been linked to decreased radiation responsiveness in human oral cancer, thus it limits efficacy of radiotherapy. To address this question, we investigated the effect of AZD2014, a novel small molecular ATP-competitive inhibitor of mTORC1 and mTORC2 kinase, as a radiosensitizer in primary OSCC and OSCC-derived cell line models.We isolated primary tumor cells from OSCC tissues and cell lines. AZD2014 was administered with and without ionizing radiation. The radiosensitizing effect of AZD2014 were then assessed using cell viability assays, clonogenic survival assays, and cell cycle analyses. Western blotting was used to detect protein expression.Combination treatment with AZD2014 and irradiation resulted in significant reduction in OSCC cell line and primary OSCC cell colony formation due to the enhanced inhibition of AKT and both mTORC1 and mTORC2 activity. Pre-treatment with AZD2014 in irradiated oral cancer cells induced tumor cell cycle arrest at the G1 and G2/M phases, which led to disruption of cyclin D1-CDK4 and cyclin B1-CDC2 complexes. Moreover, AZD2014 synergized with radiation to promote both apoptosis and autophagy by increasing caspase-3 and LC3 in primary OSCC cells.These findings suggest that in irradiated OSCC cells, co-treatment with AZD2014, which targets mTORC1 and mTORC2 blockade, is an effective radiosensitizing strategy for oral squamous cell carcinoma.

Cathepsin B Expression and the Correlation with Clinical Aspects of Oral Squamous Cell Carcinoma.

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Yang, Wei-En; Ho, Chuan-Chen; Yang, Shun-Fa; Lin, Shu-Hui; Yeh, Kun-Tu; Lin, Chiao-Wen; Chen, Mu-Kuan

2016-01-01

Cathepsin B (CTSB), a member of the cathepsin family, is a cysteine protease that is widely distributed in the lysosomes of cells in various tissues. It is overexpressed in several human cancers and may be related to tumorigenesis. The main purpose of this study was to analyze CTSB expression in oral squamous cell carcinoma (OSCC) and its correlation with patient prognosis. Tissue microarrays were used to detect CTSB expression in 280 patients and to examine the association between CTSB expression and clinicopathological parameters. In addition, the metastatic effects of the CTSB knockdown on two oral cancer cell lines were investigated by transwell migration assay. Cytoplasmic CTSB expression was detected in 34.6% (97/280) of patients. CTSB expression was correlated with positive lymph node metastasis (p = 0.007) and higher tumor grade (p = 0.008) but not with tumor size and distant metastasis. In addition, multivariate analysis using a Cox proportional hazards model revealed a higher hazard ratio, demonstrating that CTSB expression was an independent unfavorable prognostic factor in buccal mucosa carcinoma patients. Furthermore, the Kaplan-Meier curve revealed that buccal mucosa OSCC patients with positive CTSB expression had significantly shorter overall survival. Moreover, treatment with the CTSB siRNA exerted an inhibitory effect on migration in OC2 and CAL27 oral cancer cells. We conclude that CTSB expression may be useful for determining OSCC prognosis, particularly for patients with lymph node metastasis, and may function as a biomarker of the survival of OSCC patients in Taiwan.

Abrus agglutinin promotes irreparable DNA damage by triggering ROS generation followed by ATM-p73 mediated apoptosis in oral squamous cell carcinoma.

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Sinha, Niharika; Panda, Prashanta K; Naik, Prajna P; Das, Durgesh N; Mukhopadhyay, Subhadip; Maiti, Tapas K; Shanmugam, Muthu K; Chinnathambi, Arunachalam; Zayed, M E; Alharbi, Sulaiman A; Sethi, Gautam; Agarwal, Rajesh; Bhutia, Sujit K

2017-11-01

Oral cancer, a type of head and neck cancer, is ranked as one of the top most malignancies in India. Herein, we evaluated the anticancer efficacy of Abrus agglutinin (AGG), a plant lectin, in oral squamous cell carcinoma. AGG selectively inhibited cell growth, and caused cell cycle arrest and mitochondrial apoptosis through a reactive oxygen species (ROS)-mediated ATM-p73 dependent pathway in FaDu cells. AGG-induced ROS accumulation was identified as the major mechanism regulating apoptosis, DNA damage and DNA-damage response, which were significantly reversed by ROS scavenger N-acetylcysteine (NAC). Moreover, AGG was found to interact with mitochondrial manganese-dependent superoxide dismutase that might inhibit its activity and increase ROS in FaDu cells. In oral cancer p53 is mutated, thus we focused on p73; AGG resulted in p73 upregulation and knock down of p73 caused a decrease in AGG-induced apoptosis. Interestingly, AGG-dependent p73 expression was found to be regulated by ROS, which was reversed by NAC treatment. A reduction in the level of p73 in AGG-treated shATM cells was found to be associated with a decreased apoptosis. Moreover, administration of AGG (50 μg/kg body weight) significantly inhibited the growth of FaDu xenografts in athymic nude mice. In immunohistochemical analysis, the xenografts from AGG-treated mice displayed a decrease in PCNA expression and an increase in caspase-3 activation as compared to the controls. In conclusion, we established a connection among ROS, ATM and p73 in AGG-induced apoptosis, which might be useful in enhancing the therapeutic targeting of p53 deficient oral squamous cell carcinoma. © 2017 Wiley Periodicals, Inc.

Comparison of thallium-201 SPET and CT/MRI in the detection of residual/recurrent squamous cell carcinoma of the oral cavity

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Lee, Jong-Kang; Tyan, Yeu-Sheng; Huang, Wen-Sheng

2004-01-01

This study was designed to compare the effectiveness of thallium-201 single-photon emission tomography (SPET) and conventional imaging, comprising computed tomography (CT) and magnetic resonance imaging (MRI), in the detection of residual/recurrent squamous cell carcinoma (SCC) of the oral cavity. Thirty-two patients with clinically suspected recurrent SCC of the oral cavity were recruited. All patients underwent 201 Tl SPET and CT or MRI within 2 weeks. The final diagnoses were based on the histology of the biopsy specimen. 201 Tl SPET and CT/MRI both accurately detected 17 of 18 residual/recurrent tumours. CT/MRI yielded eight false-positive studies, whereas 201 Tl SPET successfully excluded all tumours. The sensitivity, specificity, positive and negative predictive values and accuracy of 201 Tl SPET for the detection of recurrent oral SCC were 94%, 100%, 100%, 93% and 97%, respectively. The sensitivity, specificity, positive and negative predictive values and accuracy of CT/MRI for the detection of recurrent oral SCC were 94%, 43%, 68%, 86% and 72%, respectively. Thallium-201 SPET is more accurate than conventional imaging (CT or MRI) in differentiating residual/recurrent oral SCC from post-therapy changes. (orig.)

Effect of the p53 gene status on the sensitivity of oral squamous cell carcinoma cells to boron neutron capture therapy

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Fujita, Y.; Kamida, A.; Kato, I.; Yura, Y.; Ono, K.; Suzuki, M.; Sakurai, Y.; Ohnishi, T.; Ohnishi, K.

2006-01-01

The role of the p53 gene in the sensitivity of oral squamous cell carcinoma (SCC) to boron neutron capture therapy (BNCT) had not been studied. We examined the effect of boronophenylalanine (BPA)-mediated BNCT on oral SCC cells showing either wild-type p53 (SAS/neo) or mutated-type p53 (SAS/mp53). Survival ratio of cells was determined by colony formation. Cell viability was measured by MTT assay. Apoptotic cells were evaluated by flow cytometric analysis and nuclear DNA staining. When SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo cells as compared with SAS/mp53. The proportion of apoptotic cells with DNA fragmentation was also increased in the cells with functional p53. These results suggest that oral SCC cells with mutated p53 cells are more resistant to BNCT than those with wild-type p53. BNCT must inhibit oral SCC cells in p53-dependent and p53-independent mechanisms. (author)

Squamous cell carcinoma of the maxillary sinus and the oral part of the upper jaw. Comparison of treatment results

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Shibuya, Hitoshi; Hoshina, Masao; Shagdarsuren, M.; Hoshi, Akihiko; Matsumoto, Satoru; Suzuki, Soji; Amagasa, Teruo

1994-01-01

The treatment results were compared in 77 patients with maxillary sinus squamous cell carcinoma (MC) and 53 patients with squamous cell carcinoma arising from the oral part of the upper law (OC). Both sets of patients received radiotherapy alone, or radiotherapy combined with surgery and/or chemotherapy. Computerized tomography was useful for the definition of the treatment volume. Intraarterial chemotherapy was given in 89 of 130 patients and in these patients the total radiation dose was reduced by about 10 Gy. No difference was found in the 5-year survival rate between the MC (65%) and the OC (66%) groups. The cumulative incidence of local failure was higher in MC (36%) than in OC (26%), whereas the ultimate incidence of neck node metastasis was higher in OC (43%) than in MC patients (18%). Half of the inoperable patients (9/18) were older than 80 years and had contraindications to anaesthesia and major surgery. The local recurrence rate was high in the inoperable MC patients (6/8). Contralateral simus cancers occurred in 4 patients in the MC group. (orig.)

Oral lichen planus (OLP), oral lichenoid lesions (OLL), oral dysplasia, and oral cancer: retrospective analysis of clinicopathological data from 2002-2011.

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Casparis, S; Borm, J M; Tektas, S; Kamarachev, J; Locher, M C; Damerau, G; Grätz, K W; Stadlinger, B

2015-06-01

This 10-year retrospective study analyzed the incidence of malignant transformation of oral lichen planus (OLP). The study also included dysplasia and oral lichenoid lesion (OLL) in the initial biopsy as a potential differential diagnosis. A total of 692 scalpel biopsies were taken from 542 patients (207 [38.2%] men and 335 [61.8%] women). Clinical and histopathological parameters were analyzed. The parameters gender (p = 0.022) and smoking behavior (p oral squamous cell carcinoma (OSCC). Smoking and joint disease appeared to be significant risk factors. Treatment with tretinoin in different concentrations (0.005-0.02%) significantly improved diagnosis. Twelve patients (8 female, 4 male) showed malignant transformation to OSCC within an average period of 1.58 years. The malignant transformation rate (MTR) was higher for OLL (4.4%) than OLP (1.2%). If the first biopsy showed intraepithelial neoplasia, the risk of developing OSCC increased (by 3.5% for squamous intraepithelial neoplasia (SIN) II and by 6.7% for SIN III). Although we cannot rule out that OLP is a premalignant oral condition, we can confirm that OLP had the lowest MTR of all diagnoses.

NDRG2 is a candidate tumor-suppressor for oral squamous-cell carcinoma

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Furuta, Hiroshi; Kondo, Yuudai [Division of Oral and Maxillofacial Surgery, Medicine of Sensory and Motor Organs, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1692 (Japan); Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1692 (Japan); Nakahata, Shingo; Hamasaki, Makoto [Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1692 (Japan); Sakoda, Sumio [Division of Oral and Maxillofacial Surgery, Medicine of Sensory and Motor Organs, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1692 (Japan); Morishita, Kazuhiro, E-mail: kmorishi@med.miyazaki-u.ac.jp [Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1692 (Japan)

2010-01-22

Oral cancer is one of the most common cancers worldwide, and squamous-cell carcinoma (OSCC) is the most common phenotype of oral cancer. Although patients with OSCC have poor survival rates and a high incidence of metastasis, the molecular mechanisms of OSCC development have not yet been elucidated. This study investigated whether N-myc downstream-regulated gene 2 (NDRG2) contributes to the carcinogenesis of OSCC, as NDRG2 is reported to be a candidate tumor-suppressor gene in a wide variety of cancers. The down-regulation of NDRG2 mRNA, which was dependent on promoter methylation, was seen in the majority of OSCC cases and in several cases of precancerous leukoplakia with dysplasia. Induction of NDRG2 expression in an HSC-3/OSCC cell line significantly inhibited cell proliferation and decreased colony formation ability on soft agar. The majority of OSCC cell lines showed an activation of PI3K/Akt signaling, and enforced expression of NDRG2 in HSC-3 cells decreased the level of phosphorylated Akt at Serine 473 (p-Akt). Immunohistochemical p-Akt staining was detected in 56.5% of the OSCC tumors, and 80.4% of the tumors were negative for NDRG2 staining. Moreover, positive p-Akt staining was inversely correlated with decreased NDRG2 expression in OSCC tumors with moderate to poor differentiation (p < 0.005). Therefore, NDRG2 is a candidate tumor-suppressor gene for OSCC development and probably contributes to the tumorigenesis of OSCC partly via the modulation of Akt signaling.

Diagnostic values of serum tumor markers Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP in oral/oropharyngeal squamous cell carcinoma.

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Yuan, Chuanshu; Yang, Kai; Tang, Hong; Chen, Dan

2016-01-01

At present, the research on serum tumor markers in the early diagnosis of malignant tumors has aroused widespread concern. The aim of this study was to investigate the diagnostic values of serum tumor markers cytokeratin 19 fragment (Cyfra21-1), squamous cell carcinoma antigen (SCCAg), ferritin, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and α-fetoprotein (AFP) for patients with oral/oropharyngeal squamous carcinoma (OSCC/OPSCC). One hundred and sixty-nine cases of patients with OSCC/OPSCC as the experimental group, 86 cases of oral benign tumor patients as the control group, and 30 cases of healthy people as the normal control group were studied. The levels of serum Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP were measured using electrochemiluminescence immunoassay. The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in patients with OSCC/OPSCC were significantly higher than those of benign tumor and healthy control group (Ptumor, and healthy group (P>0.05). The level of serum Cyfra21-1 in patients with early OSCC/OPSCC (stage I + II) was significantly higher than that of benign tumor and healthy control group (PCEA, CA19-9, and AFP showed no significant difference between patients with early OSCC/OPSCC, benign tumor, and healthy control group (P>0.05). The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in the middle-late stage of patients with OSCC/OPSCC (stage III + IV) were significantly higher than those of patients with the early OSCC/OPSCC, benign tumor, and healthy control group (PCEA were 2.17, 0.72, 109.95, and 1.99 ng/mL, respectively. The sensitivities were 60.36%, 73.37%, 81.66%, and 66.27%, respectively. The specificities were 81.03%, 68.10%, 40.52%, and 61.21%, respectively. Cyfra21-1, SCCAg, ferritin, and CEA had diagnostic values for patients with OSCC/OPSCC. Meanwhile, Cyfra21-1 had better early diagnostic value for patients with OSCC/OPSCC.

Biomarkers in molecular epidemiology study of oral squamous cell carcinoma in the era of precision medicine

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Qing-Hao Zhu

2017-01-01

Full Text Available Oral cancer, which occurs in the mouth, lips, and tongue, is a multifactorial disease whose etiology involves environment, genetic, and epigenetic factors. Tobacco use and alcohol consumption are regarded as the primary risk factors for oral squamous cell carcinoma (OSCC, and betel use, other chemicals, radiation, environmental, and genetics are reported as relevant risk factors for oral carcinogenesis. The human papillomavirus infection is an independent risk factor. Traditional epidemiology studies have revealed that environmental carcinogens are risk factors for OSCC. Molecular epidemiology studies have revealed that the susceptibility to OSCC is influenced by both environmental and genetic risk factors. However, the details and mechanisms of risk factors involved in OSCC are unclear. Advanced methods and techniques used in human genome studies provide great opportunities for researchers to explore and identify (a the details of such risk factors and (b genetic susceptibility involved in OSCC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era into the era of genome-wide association study. In the era of precision medicine, molecular epidemiology studies should focus on biomarkers for cancer genomics and their potential utility in clinical practice. Here, we briefly reviewed several molecular epidemiology studies of OSCC, focusing on biomarkers as valuable utility in risk assessment, clinical screening, diagnosis, and prognosis prediction of OSCC in the era of precision medicine.

Expression of cyclo-oxygenase-2 enzyme in the tissue samples of patients with various clinicopathological stages of oral leukoplakia and oral squamous cell carcinoma

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Nelson Aruldoss

2016-01-01

Full Text Available Aim: The purpose of this study was to evaluate the expression of cyclo-oxygenase-2 (COX-2 enzyme in the tissue samples of patients with various clinicopathological stages of oral leukoplakia and oral squamous cell carcinoma (OSCC. Materials and Methods: The samples for the study were divided into 4 groups. Group A comprised 20 healthy individuals with no habits. Twenty healthy individuals with habitual tobacco usage and no oral lesions were included in Group B. Twenty cases of leukoplakia diagnosed clinically and histopathologically were included in Group C. Staging was done using the modified classification and staging system of oral leukoplakia. Twenty cases of OSCC diagnosed clinically and histopathologically were included in Group D. Immunohistochemical staining was done on these 80 samples (paraffin blocks for COX-2 expression by indirect method using polymer based Horseradish peroxidase system. Statistical analysis was performed using Kruskal-Wallis test and Spearman′s rank correlation test. Results: Significant and proportional increase of COX-2 staining was noted with the increase in the severity of dysplasia. Eighty percent of OSCC expressed COX-2, increasing in its intensity of staining with the decrease in differentiation. Seventy five percent of leukoplakia showed positive COX-2 expression. Only 15% of positive controls were COX-2 positive. No normal mucosa showed positive expression of COX-2. Conclusion: High expression of COX-2 is seen in advanced stages of leukoplakia and OSCC. Hence, COX-2 enzyme increases cell proliferation, promotes angiogenesis and inhibits immune surveillance in carcinogenesis; it can be an early detection marker in oral leukoplakia and a prognostic marker of OSCC.

Sentinel lymph node biopsy in oral and oropharyngeal squamous cell carcinoma: current status and unresolved challenges

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Bluemel, Christina; Herrmann, Ken [University Hospital of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Rubello, Domenico [Rovigo Hospital, Department of Nuclear Medicine-PET/CT Oncologic and Endocrine Sections, Rovigo (Italy); Colletti, Patrick M. [University of Southern California, Department of Radiology, Los Angeles, CA (United States); Bree, Remco de [UMC Utrecht Cancer Center, Department of Head and Neck Surgical Oncology, Utrecht (Netherlands)

2015-08-15

Because imaging with ultrasound, computed tomography, magnetic resonance imaging or positron emission tomography is unreliable for preoperative lymph node staging of early-stage oral and oropharyngeal squamous cell carcinoma (OSCC), elective neck dissection has been typically performed. The targeted sampling of sentinel lymph nodes (SLN) identified by lymphoscintigraphy and detected by gamma probe has become an effective alternative for the selection of patients for regional nodal resection. With careful consideration to technique, high SLN detection rates have been reported. Advanced techniques including intraoperative handheld gamma camera imaging and freehand single photon emission computed tomography (SPECT) are expected to increase surgical confidence in these procedures. This review gives an update on SLN biopsy in patients with OSCC including clinical standards and controversial aspects. (orig.)

Oral Squamous Cell Carcinoma Found Inline with the Fields of Repeat Stereotactic Radiosurgery for Recurrent Trigeminal Neuralgia.

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Berti, Aldo; Granville, Michelle; Jacobson, Robert E

2018-01-12

A case of an extremely healthy, active, 96-year-old patient, nonsmoker, is reviewed. He was initially treated for left V1, V2, and V3 trigeminal neuralgia in 2001, at age 80, with stereotactic radiosurgery (SRS) with a dose of 80 Gy to the left retrogasserian trigeminal nerve. He remained asymptomatic for nine years until his trigeminal pain recurred in 2010. He was first treated medically but was intolerant to increasing doses of carbamazepine and gabapentin. He underwent a second SRS in 2012 with a dose of 65.5 Gy to the same retrogasserian area of the trigeminal nerve, making the total cumulative dose 125.5 Gy. In late 2016, four years after the 2 nd SRS, he was found to have invasive keratinizing squamous cell carcinoma in the left posterior mandibular oral mucosa. Keratinizing squamous cell carcinoma is seen primarily in smokers or associated with the human papillomavirus, neither of which was found in this patient. A review of his two SRS plans shows that the left lower posterior mandibular area was clearly within the radiation fields for both SRS treatments. It is postulated that his cancer developed secondary to the long-term radiation effect with a very localized area being exposed twice to a focused, cumulative, high-dose radiation. There are individual reports in the literature of oral mucositis immediately after radiation for trigeminal neuralgia and the delayed development of malignant tumors, including glioblastoma found after SRS for acoustic neuromas, but there are no reports of delayed malignant tumors developing within the general radiation field. Using repeat SRS is an accepted treatment for recurrent trigeminal neuralgia, but physicians and patients should be aware of the potential effects of higher cumulative radiation effects within the treatment field when patients undergo repeat procedures.

Cervical lymph node metastasis of oral squamous cell carcinomas. CT enhancement and histopathological evaluations

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Etoh, Yohei; Kimura, Takuji; Sasaki, Akira; Kishimoto, Koji; Matsumura, Tomohiro; Kishi, Kanji [Okayama Univ. (Japan). Dental School

2000-06-01

A comparison of the results of histopathological and enhanced CT examinations were carried out for 88 patients with oral squamous cell carcinomas who underwent neck dissection. CT scanning (5-mm thick section) images obtained during bolus/drip injection of Iopamidol were routinely taken through the neck. Ninety-two of 1634 nodes were histologically diagnosed as metastatic. Low density areas surrounding enhancement rims were metastatic nodal central necrosis or keratinization. Enhanced areas in many metastatic nodes were considered to be lymphatic architecture, not metastatic masses especially in the avascular keratinization. Enhanced CT produced accurate information of lymph node size, location, shape, grouping and spread from nodes to adjacent structures. However, it was considered that not every metastatic lymph node should show enlargement and/or enhancement. Improved assessment of solid metastatic features of lymph nodes (shape, size, and involvement) may be achieved with the aid of thin-thickness CT. (author)

Cervical lymph node metastasis of oral squamous cell carcinomas. CT enhancement and histopathological evaluations

International Nuclear Information System (INIS)

Etoh, Yohei; Kimura, Takuji; Sasaki, Akira; Kishimoto, Koji; Matsumura, Tomohiro; Kishi, Kanji

2000-01-01

A comparison of the results of histopathological and enhanced CT examinations were carried out for 88 patients with oral squamous cell carcinomas who underwent neck dissection. CT scanning (5-mm thick section) images obtained during bolus/drip injection of Iopamidol were routinely taken through the neck. Ninety-two of 1634 nodes were histologically diagnosed as metastatic. Low density areas surrounding enhancement rims were metastatic nodal central necrosis or keratinization. Enhanced areas in many metastatic nodes were considered to be lymphatic architecture, not metastatic masses especially in the avascular keratinization. Enhanced CT produced accurate information of lymph node size, location, shape, grouping and spread from nodes to adjacent structures. However, it was considered that not every metastatic lymph node should show enlargement and/or enhancement. Improved assessment of solid metastatic features of lymph nodes (shape, size, and involvement) may be achieved with the aid of thin-thickness CT. (author)

Relationship among tobacco habits, human papilloma virus (HPV) infection, p53 polymorphism/mutation and the risk of oral squamous cell carcinoma

OpenAIRE

Bidyut Chakrobarty; Jay Gopal Roy; Sumit Majumdar; Divya Uppala

2014-01-01

The prevalence of oral squamous cell carcinoma (OSCC) has significantly increased over decades in several countries and human papilloma virus (HPV) has been indicated as one of the underlying causes. This suggests that HPV plays a role in the early stages of carcinogenesis but is not a requisite for the maintenance and progression of malignant state. p53 is a tumor suppressor gene that checks the cell and promotes apoptosis and cell repair that can be deactivated by mutations and a viral inte...

Diagnostic values of serum tumor markers Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP in oral/oropharyngeal squamous cell carcinoma

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Yuan CS

2016-06-01

Full Text Available Chuanshu Yuan, Kai Yang, Hong Tang, Dan Chen Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: At present, the research on serum tumor markers in the early diagnosis of malignant tumors has aroused widespread concern. The aim of this study was to investigate the diagnostic values of serum tumor markers cytokeratin 19 fragment (Cyfra21-1, squamous cell carcinoma antigen (SCCAg, ferritin, carcinoembryonic antigen (CEA, carbohydrate antigen 19-9 (CA19-9, and α-fetoprotein (AFP for patients with oral/oropharyngeal squamous carcinoma (OSCC/OPSCC. Methods: One hundred and sixty-nine cases of patients with OSCC/OPSCC as the experimental group, 86 cases of oral benign tumor patients as the control group, and 30 cases of healthy people as the normal control group were studied. The levels of serum Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP were measured using electrochemiluminescence immunoassay. Results: The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in patients with OSCC/OPSCC were significantly higher than those of benign tumor and healthy control group (P<0.05. The levels of CA19-9 and AFP showed no significant difference between patients with OSCC/OPSCC, benign tumor, and healthy group (P>0.05. The level of serum Cyfra21-1 in patients with early OSCC/OPSCC (stage I + II was significantly higher than that of benign tumor and healthy control group (P<0.05. However, the levels of serum SCCAg, ferritin, CEA, CA19-9, and AFP showed no significant difference between patients with early OSCC/OPSCC, benign tumor, and healthy control group (P>0.05. The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in the middle-late stage of patients with OSCC/OPSCC (stage III + IV were significantly higher than those of patients with the early OSCC/OPSCC, benign tumor, and healthy control group (P<0.05. The diagnostic cutoff levels of Cyfra21

Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients

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2010-01-01

The incidence of oral squamous cell carcinoma remains high. Oral and oro-pharyngeal carcinomas are the sixth most common cancer in the world. Several clinicopathological parameters have been implicated in prognosis, recurrence and survival, following oral squamous cell carcinoma. In this retrospective analysis, clinicopathological parameters of 115 T1/T2 OSCC were studied and compared to recurrence and death from tumour-related causes. The study protocol was approved by the Joint UCL/UCLH committees of the ethics for human research. The patients' data was entered onto proformas, which were validated and checked by interval sampling. The fields included a range of clinical, operative and histopathological variables related to the status of the surgical margins. Data collection also included recurrence, cause of death, date of death and last clinic review. Causes of death were collated in 4 categories (1) death from locoregional spread, (2) death from distant metastasis, (3) death from bronchopulmonary pneumonia, and (4) death from any non-tumour event that lead to cardiorespiratory failure. The patients' population comprised 65 males and 50 females. Their mean age at the 1st diagnosis of OSCC was 61.7 years. Two-thirds of the patients were Caucasians. Primary sites were mainly identified in the tongue, floor of mouth (FOM), buccal mucosa and alveolus. Most of the identified OSCCs were low-risk (T1N0 and T2N0). All patients underwent primary resection ± neck dissection and reconstruction when necessary. Twenty-two patients needed adjuvant radiotherapy. Pathological analysis revealed that half of the patients had moderately differentiated OSCC. pTNM slightly differed from the cTNM and showed that 70.4% of the patients had low-risk OSCC. Tumour clearance was ultimately achieved in 107 patients. Follow-up resulted in a 3-year survival of 74.8% and a 5-year survival of 72.2%. Recurrence was identified in 23 males and 20 females. The mean age of 1st diagnosis of the

Immunohistochemical expression of p53, p16 and hTERT in oral squamous cell carcinoma and potentially malignant disorders

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Aline Correa Abrahao

2011-02-01

Full Text Available Oral carcinogenesis is a multi-step process. One possible step is the development of potentially malignant disorders known as leukoplakia and erytroplakia. The objective of this study was to use immunohistochemistry to analyze the patterns of expression of the cell-cycle regulatory proteins p53 and p16INK4a in potentially malignant disorders (PMD of the oral mucosa (with varying degrees of dysplasia and in oral squamous cell carcinomas (OSCC to correlate them with the expression of telomerase (hTERT. Fifteen PMD and 30 OSCC tissue samples were analyzed. Additionally, 5 cases of oral epithelial hyperplasia (OEH were added to analyze clinically altered mucosa presenting as histological hyperplasia without dysplasia. p53 positivity was observed in 93.3% of PMD, in 63.3% of OSCC and in 80% of OEH. Although there was no correlation between p53 expression and the grade of dysplasia, all cases with severe dysplasia presented p53 suprabasal immunoexpression. p16INK4a expression was observed in 26.7% of PMD, in 43.3% of OSCC and in 2 cases of OEH. The p16INK4a expression in OEH, PMD and OSCC was unable to differentiate non-dysplastic from dysplastic oral epithelium. hTERT positivity was observed in all samples of OEH and PMD and in 90% of OSCC. The high hTERT immunoexpression in all three lesions indicates that telomerase is present in clinically altered oral mucosa but does not differentiate hyperplastic from dysplastic oral epithelium. In PMD of the oral mucosa, the p53 immunoexpression changes according to the degree of dysplasia by mechanisms independent of p16INK4a and hTERT.

Phenotypic plasticity and epithelial-to-mesenchymal transition in the behaviour and therapeutic response of oral squamous cell carcinoma.

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Vig, Navin; Mackenzie, Ian C; Biddle, Adrian

2015-10-01

It is increasingly recognised that phenotypic plasticity, apparently driven by epigenetic mechanisms, plays a key role in tumour behaviour and markedly influences the important processes of therapeutic survival and metastasis. An important source of plasticity in malignancy is epithelial-to-mesenchymal transition (EMT), a common epigenetically controlled event that results in transition of malignant cells between different phenotypic states that confer motility and enhance survival. In this review, we discuss the importance of phenotypic plasticity and its contribution to cellular heterogeneity in oral squamous cell carcinoma with emphasis on aspects of drug resistance and EMT. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prosthetic Rehabilitation After Fibular Free Flap Surgery of Mandibular Defects in a Patient With Oral Squamous Cell Carcinoma.

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Yoon, Hyung-In

2016-10-01

This report is to present the treatment procedure and clinical considerations of prosthodontic management of a patient who had undergone a partial mandibulectomy and fibular free flap surgery. A 59-year-old man with a squamous cell carcinoma received a partial mandibular resection. Microsurgical reconstruction with a fibular free flap surgery and implant-supported zirconia-fixed prosthesis produced by computer-aided manufacturing led to successful results for the oral rehabilitation of mandibular defects. The implant-supported zirconia-fixed prosthesis can be recommended for use in patients with mandibulectomy and fibular free flaps. Close cooperation between the surgeon and the prosthodontist is mandatory for the satisfaction of the patient.

Caveolin-1 expression in oral lichen planus, dysplastic lesions and squamous cell carcinoma.

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Jaafari-Ashkavandi, Zohreh; Aslani, Ehsan

2017-07-01

Caveolin-1(Cav-1), the main part of caveolae structure, is supposed to play a role in pathogenesis of many human tumors. Since oral lichen planus (OLP) is considered as a potential premalignant disease, this study evaluated Cav-1 expression in OLP in comparison with benign hyperkeratosis, dysplastic epithelium and oral squamous cell carcinoma (OSCC), to investigate its possible role in pathogenesis and malignant transformation of OLP. In this cross-sectional retrospective study, immunohistochemical expression of Cav-1 in the epithelial component and stroma was evaluated in 81 samples, including 12 cases of hyperkeratosis, 24 OLP, 22 epithelial dysplasia, and 23 OSCC samples. Correlations between Cav-1 expression and clinicopathological variables were evaluated statistically. Positive Cav-1 staining was found in 58% of OLP, 91% of hyperkeratosis, 100% of epithelial dysplasia, and 95% of OSCC samples. OSCC showed the highest Cav-1 expression and OLP had the lowest (P=0.001). The intensity of staining was significantly increased in stepwise manner from OLP to OSCC (P=0.001). Expression of Cav-1 was related to the grade of samples in OSCC and dysplastic samples (P=0.04). Based on the findings, it was concluded that Cav-1 may play a role in the pathogenesis of OLP and carcinogenesis of SCC, but its role in malignant transformation of OLP is not confirmed. Further studies are needed to evaluate its potential therapeutic function in OLP and SCC. Copyright © 2017 Elsevier GmbH. All rights reserved.

Human MutL homolog 1 immunoexpression in oral leukoplakia and oral squamous cell carcinoma: A prospective study in Indian population

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Chaudhari, Narendra T; Tupkari, Jagdish V; Joy, Tabita; Ahire, Manisha S

2016-01-01

Background: Mammalian mismatch repair system is responsible for maintaining genomic stability during repeated duplications, and human MutL homolog 1 (hMLH1) protein constitutes an important part of it. Various isolated studies have reported the altered expression of hMLH1 in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). Research is lacking in the quantitative estimation and comparison of hMLH1 expression in OL and OSCC. Aims: To evaluate, quantify and compare hMLH1 immunoexpression in normal oral mucosa, OL and OSCC. Settings and Design: Thirty patients of OL and thirty patients of OSCC formed the study group and thirty patients were included in the control group (normal oral mucosa). Formalin-fixed paraffin wax blocks were prepared from the tissue samples. Materials and Methods: Immunohistochemistry for hMLH1 was performed, and the total number of positive cells was counted in high-power fields, and based on that percentage positivity of hMLH1 was calculated in all the cases. Statistical Analysis: Kruskal–Wallis and t-test were used. P < 0.05 was considered to be statistically significant. Results: The mean hMLH1 value in control group, leukoplakia and OSCC was 78.26, 54.33 and 40.97 respectively. hMLH1 immunoexpression showed decreasing indexes from control group to leukoplakia and then further to OSCC. hMLH1 expression was significantly lower in OSCC as compared to leukoplakia. There was no significant correlation of mean hMLH1 expression between different clinical and histopathological stages of leukoplakia and OSCC. Conclusions: hMLH1 immunoexpression was inversely related to the degree of dysplasia. These findings suggest that there is a progressive decrease in hMLH1 expression from control to leukoplakia and further to OSCC. Thus, it can be concluded that hMLH1 can be used as a reliable biomarker for malignant transformation. PMID:27721611

CLINICO-EPIDEMIOLOGICAL PROFILE OF ORAL CANCER: A HOSPITAL BASED STUDY

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Kapil H Agrawal

2012-07-01

common site for oral cancer was tongue. Histopathologically 52 (32.5% cases were well differentiated squamous cell carcinoma, 37 (23% cases were moderately differentiated squamous cell carcinoma and 34 (21% cases as poorly differentiated squamous cell carcinoma. 37 (23% cases were diagnosed as Oral Verrucous Carcinoma (a rare variant of Oral Squamous Cell Carcinoma. 72% cases were in either stage II or stage III. Conclusions: The most common site for oral cancer was tongue and histopathologically majority of the cases were well differentiated squamous cell carcinoma presented in advanced stages of disease. We observed higher proportion of oral cancers among young patients (below 40 years. Proportion of Oral Verrucous Carcinoma (OVC which is a rare variant of Oral Squamous Cell Carcinoma was also high in the study.

Construction of a pathological risk model of occult lymph node metastases for prognostication by semi-automated image analysis of tumor budding in early-stage oral squamous cell carcinoma

DEFF Research Database (Denmark)

Pedersen, Nicklas Juel; Jensen, David Hebbelstrup; Lelkaitis, Giedrius

2017-01-01

It is challenging to identify at diagnosis those patients with early oral squamous cell carcinoma (OSCC), who have a poor prognosis and those that have a high risk of harboring occult lymph node metastases. The aim of this study was to develop a standardized and objective digital scoring method...

Immunohistochemical study of integrin α₅β₁, fibronectin, and Bcl-2 in normal oral mucosa, inflammatory fibroepithelial hyperplasia, oral epithelial dysplasia, and oral squamous cell carcinoma.

Science.gov (United States)

Núñez, Manuel Antonio Gordón; de Matos, Felipe Rodrigues; Freitas, Roseana de Almeida; Galvão, Hébel Cavalcanti

2013-07-01

The objective of this study was to compare the immunoexpression of integrin α₅β₁, fibronectin, and the Bcl-2 protein in normal oral mucosa (NOM), inflammatory fibroepithelial hyperplasia (IFH), oral epithelial dysplasia (OED), and oral squamous cell carcinoma (OSCC). Eleven cases of NOM, 16 IFH, 20 OED, and 27 OSCC were selected for analysis of the immunoexpression of integrin α₅β₁, fibronectin, and bcl-2 protein. There was an association between the intensity and location of the integrin α₅β₁ expression, especially in the OSCC, that 48.1% of cases showed weak immunoreactivity and 40.7% in the suprabasal layer (P < 0.05). There was an association between the pattern and distribution of fibronectin expression in basement membrane, where 90% of NOM showed a pattern of linear continuous and 80% of OED exhibited focal distribution (P < 0.05). The fibronectin expression in connective tissue was predominantly intense with an association of staining pattern among the different specimens, where 37% of OSCC showed a reticular pattern (P < 0.05). There was an association of bcl-2 protein among the types of specimens, especially in IFH and OSCC, where 100% of the cases exhibited scores 1 of staining (P < 0.05). Within this context, the interaction of integrin α₅β₁ with its main ligand in the extracellular matrix, fibronectin, is suggested to influence the survival of tumor cells and to favor their proliferation by modulating apoptosis through the upregulation of antiapoptotic proteins or the suppression of apoptotic mediators.

Nitric oxide synthase 2 (NOS2) expression in histologically normal margins of oral squamous cell carcinoma.

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Morelatto, Rosana; Itoiz, María-Elina; Guiñazú, Natalia; Piccini, Daniel; Gea, Susana; López-de Blanc, Silvia

2014-05-01

The activity of Nitric Oxide Synthase 2 (NOS2) was found in oral squamous cell carcinomas (OSCC) but not in normal mucosa. Molecular changes associated to early carcinogenesis have been found in mucosa near carcinomas, which is considered a model to study field cancerization. The aim of the present study is to analyze NOS2 expression at the histologically normal margins of OSCC. Eleven biopsy specimens of OSCC containing histologically normal margins (HNM) were analyzed. Ten biopsies of normal oral mucosa were used as controls. The activity of NOS2 was determined by immunohistochemistry. Salivary nitrate and nitrite as well as tobacco and alcohol consumption were also analyzed. The Chi-squared test was applied. Six out of the eleven HNM from carcinoma samples showed positive NOS2 activity whereas all the control group samples yielded negative (p=0.005). No statistically significant association between enzyme expression and tobacco and/or alcohol consumption and salivary nitrate and nitrite was found. NOS2 expression would be an additional evidence of alterations that may occur in a state of field cancerization before the appearance of potentially malignant morphological changes.

Relationship among tobacco habits, human papilloma virus (HPV) infection, p53 polymorphism/mutation and the risk of oral squamous cell carcinoma.

Science.gov (United States)

Chakrobarty, Bidyut; Roy, Jay Gopal; Majumdar, Sumit; Uppala, Divya

2014-05-01

The prevalence of oral squamous cell carcinoma (OSCC) has significantly increased over decades in several countries and human papilloma virus (HPV) has been indicated as one of the underlying causes. This suggests that HPV plays a role in the early stages of carcinogenesis but is not a requisite for the maintenance and progression of malignant state. p53 is a tumor suppressor gene that checks the cell and promotes apoptosis and cell repair that can be deactivated by mutations and a viral interaction leading to cancer and individuals with particular polymorphic variant of p53 is more susceptible to HPV-induced carcinogenesis. The present study has been carried out to detect and correlate p53 polymorphism/mutation, HPV DNA in the biopsy samples of oral cancer patients who had tobacco habits.

The pathological significance of Notch1 in oral squamous cell carcinoma.

Science.gov (United States)

Yoshida, Ryoji; Nagata, Masashi; Nakayama, Hideki; Niimori-Kita, Kanako; Hassan, Wael; Tanaka, Takuji; Shinohara, Masanori; Ito, Takaaki

2013-10-01

Notch signaling has been reported to be involved in several types of malignant tumors; however, the role and activation mechanism of Notch signaling in oral squamous cell carcinoma (OSCC) remains poorly characterized. The purpose of this study was to elucidate the pathological significance of Notch signaling and its activation mechanism in the development and progression of OSCC. In this study, we showed that the expression of Notch1 and intracellular Notch domain (NICD) are upregulated in OSCCs. In addition, Notch1 and NICD were found to be characteristically localized at the invasive tumor front. TNF-α, a major inflammatory cytokine, significantly activated Notch signaling in vitro. In a clinicopathological analysis, Notch1 expression correlated with both the T-stage and the clinical stage. Furthermore, loss of Notch1 expression correlated with the inhibition of cell proliferation and TNF-α-dependent invasiveness in an OSCC cell line. In addition, γ-secretase inhibitor (GSI) prevented cell proliferation and TNF-α-dependent invasion of OSCC cells in vitro. These results indicate that altered expression of Notch1 is associated with increased cancer progression and that Notch1 regulates the steps involved in cell metastasis in OSCC. Moreover, inactivating Notch signaling with GSI could therefore be a useful approach for treating patients with OSCC.

Foxp3 overexpression in tumor cells predicts poor survival in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Song, Jing-Jing; Zhao, Si-Jia; Fang, Juan; Ma, Da; Liu, Xiang-Qi; Chen, Xiao-Bing; Wang, Yun; Cheng, Bin; Wang, Zhi

2016-01-01

Forkhead Box P3 (Foxp3) is a regulatory T cells marker, and its expression correlates with prognosis in a number of malignancies. The aim of this study is to determine the relationship of Foxp3 expression with clinicopathological parameters and prognosis in oral squamous cell carcinoma (OSCC). Foxp3 expression was examined using immunohistochemistry (IHC) in paraffin-embedded tissue samples from 273 OSCC patients. Statistical analysis was performed to evaluate the associations between Foxp3 expression, the clinicopathologic characteristics and prognostic factors in OSCC. Foxp3 protein expression was significantly associated with lymph node metastasis (P <0.01). Both univariate and multivariate analyses revealed that Foxp3 was an independent factor for both 5 years overall survival (OS) and relapse-free survival (RFS) (both P <0.01). Patients with Foxp3 overexpression had shorter OS and RFS. Our results determined that elevated Foxp3 protein expression was a predictive factor of outcome in OSCC and could act as a promising therapeutic target

Combined therapy for non-resectable squamous cell carcinoma of the oral cavity

International Nuclear Information System (INIS)

Noorman van der Dussen, M.F.

1986-01-01

A promising way to acquire information about individual tumour behaviour seems to be the determination of cell kinetic properties and, even more importantly, the changes they undergo during treatment. Ideally, knowledge of changes in cell cycle at all times is desirable so that optimal regulation of the chosen chemotherapy and/or radiotherapy could lead to maximal cell death of the tumour cells with minimal toxicity for the host cells. A possible gain for increasing insight into the characteristics of a particular tumour is DNA flow cytometry. By taking multiple biopsies before and during the chemotherapy/radiotherapy treatment, it is perhaps possible to predict the expected clinical results. Research relating to this is described in this dissertation: 16 patients with non-resectable tumours of the oral cavity were treated with concurrent intra-arterial chemotherapy and radiotherapy. Multiple biopsies were analyzed with DNA flow cytometry and an attempt was made to correlate the clinical response with the acquired cellular kinetic data. The purpose of the research can be summarized as: 1. Is regional cure of non-resectable squamous cell carcinomas possible using the method described? 2. Is it possible, using DNA flow cytometry, to predict the chance of successful therapy? (Auth.)

Synchronous malignancies in patients with squamous cell carcinomas of the oral cavity

Energy Technology Data Exchange (ETDEWEB)

Liu, Feng-Yuan [Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Department of Nuclear Medicine, Chiayi (China); Liao, Chun-Ta [Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Department of Otorhinolaryngology, Head and Neck Surgery, Taoyuan (China); Yen, Tzu-Chen [Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Department of Nuclear Medicine and Molecular Imaging Center, Taoyuan County (China)

2011-06-15

Synchronous malignancies in patients with squamous cell carcinomas of the oral cavity (OCSCC) are occasionally encountered. In the current study we tried to evaluate their frequency, detectability by {sup 18}F-fluorodeoxyglucose (FDG) studies, and prognostic factors. A retrospective analysis of patients with primary OCSCC enrolled for {sup 18}F-FDG studies from 2002 to 2008 was performed. The detectability of synchronous second cancers by {sup 18}F-FDG studies was defined by the scoring of two interpreters. Prognostic factors for overall survival in patients receiving curative-intent treatment were assessed using the univariate Kaplan-Mayer analysis and the multivariate Cox regression model. Of 764 patients, 40 (5.2%) had synchronous malignancies. {sup 18}F-FDG studies detected 22 (48%) of 46 synchronous second cancers. For synchronous cancers at the hypopharynx, esophagus, or liver, the median survival of patients was no longer than 1 year, and the detection rates by {sup 18}F-FDG studies were 100, 86, and 25%, respectively. In the 33 patients receiving curative-intent treatment, the site of second cancer, complete surgical resection of all known tumors, and the oral habit of betel quid/areca nut chewing are significant prognostic factors in the univariate analysis, while the site of second cancer is the only significant prognostic factor in the multivariate analysis (p = 0.041). The site of second cancer is the most significant prognostic factor in OCSCC patients with synchronous malignancies receiving curative-intent treatment. {sup 18}F-FDG studies detect synchronous malignancies with poor prognosis in OCSCC patients except for hepatic cancers. In OCSCC patients with synchronous malignancies with poor prognosis, prospective studies comparing different treatment options should be further conducted. (orig.)

Synchronous malignancies in patients with squamous cell carcinomas of the oral cavity

International Nuclear Information System (INIS)

Liu, Feng-Yuan; Liao, Chun-Ta; Yen, Tzu-Chen

2011-01-01

Synchronous malignancies in patients with squamous cell carcinomas of the oral cavity (OCSCC) are occasionally encountered. In the current study we tried to evaluate their frequency, detectability by 18 F-fluorodeoxyglucose (FDG) studies, and prognostic factors. A retrospective analysis of patients with primary OCSCC enrolled for 18 F-FDG studies from 2002 to 2008 was performed. The detectability of synchronous second cancers by 18 F-FDG studies was defined by the scoring of two interpreters. Prognostic factors for overall survival in patients receiving curative-intent treatment were assessed using the univariate Kaplan-Mayer analysis and the multivariate Cox regression model. Of 764 patients, 40 (5.2%) had synchronous malignancies. 18 F-FDG studies detected 22 (48%) of 46 synchronous second cancers. For synchronous cancers at the hypopharynx, esophagus, or liver, the median survival of patients was no longer than 1 year, and the detection rates by 18 F-FDG studies were 100, 86, and 25%, respectively. In the 33 patients receiving curative-intent treatment, the site of second cancer, complete surgical resection of all known tumors, and the oral habit of betel quid/areca nut chewing are significant prognostic factors in the univariate analysis, while the site of second cancer is the only significant prognostic factor in the multivariate analysis (p = 0.041). The site of second cancer is the most significant prognostic factor in OCSCC patients with synchronous malignancies receiving curative-intent treatment. 18 F-FDG studies detect synchronous malignancies with poor prognosis in OCSCC patients except for hepatic cancers. In OCSCC patients with synchronous malignancies with poor prognosis, prospective studies comparing different treatment options should be further conducted. (orig.)

Detection of oral squamous cell carcinoma metastasis with cathepsin D: An immunohistochemical approach

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Seema Kapoor

2014-01-01

Full Text Available Background: The lysosomal protease cathepsin D (CD has been associated with tumor progression in malignant tumors including oral squamous cell carcinoma (OSCC. The purpose of this study was to find out any association between the CD and lymph node metastasis and to study the correlation of CD with various clinicopathological parameters to aid in assessment of its role as a prognostic indicator. Materials and Methods: Immunohistochemical staining was performed on 20 OSCC samples with polyclonal antibody against CD. Positive results indicative of the presence of CD were further analyzed to determine any correlation between the CD and other clinicopathological parameters. Pearson Chi-square analyses, Spearsman correlation coefficient, Mann-Whitney test, Kruskal Wallis test and student t test were used for statistical analysis (P < 0.05. Results: Patients with lymph node metastasis showed statistically significant increase in CD expression (P < 0.01. Increasing tumor size seemed to correlate with increased CD expression (P < 0.05. Conclusion: Based on its association with other clinicopathological variables, CD expression can be used for the assessment of patient survival in cases of OSCC.

Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma

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Adrian Biddle

2016-02-01

Full Text Available Cancer stem cells (CSCs drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT and mesenchymal-to-epithelial transition (MET to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC, we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/−CD24+ cell surface marker profile. Treatment with TGFβ and retinoic acid (RA enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma.

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Biddle, Adrian; Gammon, Luke; Liang, Xiao; Costea, Daniela Elena; Mackenzie, Ian C

2016-02-01

Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44(high)EpCAM(low/-) CD24(+) cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

A Real-Time Near-Infrared Fluorescence Imaging Method for the Detection of Oral Cancers in Mice Using an Indocyanine Green-Labeled Podoplanin Antibody.

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Ito, Akihiro; Ohta, Mitsuhiko; Kato, Yukinari; Inada, Shunko; Kato, Toshio; Nakata, Susumu; Yatabe, Yasushi; Goto, Mitsuo; Kaneda, Norio; Kurita, Kenichi; Nakanishi, Hayao; Yoshida, Kenji

2018-01-01

Podoplanin is distinctively overexpressed in oral squamous cell carcinoma than oral benign neoplasms and plays a crucial role in the pathogenesis and metastasis of oral squamous cell carcinoma but its diagnostic application is quite limited. Here, we report a new near-infrared fluorescence imaging method using an indocyanine green (ICG)-labeled anti-podoplanin antibody and a desktop/a handheld ICG detection device for the visualization of oral squamous cell carcinoma-xenografted tumors in nude mice. Both near-infrared imaging methods using a desktop (in vivo imaging system: IVIS) and a handheld device (photodynamic eye: PDE) successfully detected oral squamous cell carcinoma tumors in nude mice in a podoplanin expression-dependent manner with comparable sensitivity. Of these 2 devices, only near-infrared imaging methods using a handheld device visualized oral squamous cell carcinoma xenografts in mice in real time. Furthermore, near-infrared imaging methods using the handheld device (PDE) could detect smaller podoplanin-positive oral squamous cell carcinoma tumors than a non-near-infrared, autofluorescence-based imaging method. Based on these results, a near-infrared imaging method using an ICG-labeled anti-podoplanin antibody and a handheld detection device (PDE) allows the sensitive, semiquantitative, and real-time imaging of oral squamous cell carcinoma tumors and therefore represents a useful tool for the detection and subsequent monitoring of malignant oral neoplasms in both preclinical and some clinical settings.

Size of cervical lymph node and metastasis in squamous cell carcinoma of the oral tongue and floor of mouth.

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Jarungroongruangchai, Weerawut; Charoenpitakchai, Mongkol; Silpeeyodom, Tawatchai; Pruksapong, Chatchai; Burusapat, Chairat

2014-02-01

Squamous cell carcinoma (SCC) of the oral tongue and floor of mouth are the most common head and neck cancers. Regional metastasis of SCC is most likely found at the cervical lymph node. Size and characteristics of pathologically suspicious lymph nodes are related to the aggressiveness of the primary tumor: The objective of this study is to analyze the conrrelation between sizes of cervical node and metastasis in SCC of oral tongue and floor of mouth. Retrospective review was conducted firom the patient's charts between January 2008 and December 2012. Clinical, histopathology and surgical records were reviewed. Cervical lymph nodes ofSCC of oral tongue and floor of mouth were reviewed and divided into four groups depending on their size (1-5 mm, 6-9 mm, 10-30 mm and more than 30 am,). A p-value oral cavity were recorded. Sixteen patients ofSCC of the oral tongue and 15patients of SCC of the floor of mouth underwent neck dissection (641 cervical nodes). Most ofthe patients were diagnosed with stage 3 (41.94%). Extracapsular extension was found in 72.15% of SCC of oral tongue and 73.33 % of SCC ofthe floor of mouth. Size of cervical lymph nodes less than 10 mm was found to be metastasis at 9.27% and 10.82% of SCC of oral tongue and floor of mouth, respectively. Cervical node metastasis can be found in SCC of the oral tongue and floor ofmouth with clinlically negative node andsize of cervical node less than 10 mm. Here in, size of cervical node less than 10 mm was still important due to the chance for metastasis especially high grade tumors, advanced stage cancer and lymphovascular invasion.

Heterogeneity, histological features and DNA ploidy in oral carcinoma by image-based analysis.

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Diwakar, N; Sperandio, M; Sherriff, M; Brown, A; Odell, E W

2005-04-01

Oral squamous carcinomas appear heterogeneous on DNA ploidy analysis. However, this may be partly a result of sample dilution or the detection limit of techniques. The aim of this study was to determine whether oral squamous carcinomas are heterogeneous for ploidy status using image-based ploidy analysis and to determine whether ploidy status correlates with histological parameters. Multiple samples from 42 oral squamous carcinomas were analysed for DNA ploidy using an image-based system and scored for histological parameters. 22 were uniformly aneuploid, 1 uniformly tetraploid and 3 uniformly diploid. 16 appeared heterogeneous but only 8 appeared to be genuinely heterogeneous when minor ploidy histogram peaks were taken into account. Ploidy was closely related to nuclear pleomorphism but not differentiation. Sample variation, detection limits and diagnostic criteria account for much of the ploidy heterogeneity observed. Confident diagnosis of diploid status in an oral squamous cell carcinoma requires a minimum of 5 samples.

Superselective intra-arterial infusion chemotherapy for stage III/IV squamous cell carcinomas of the oral cavity: Midterm results

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Ikushima, I.; Korogi, Y.; Ishii, A.; Hirai, T.; Yamura, M.; Nishimura, R.; Baba, Y.; Yamashita, Y.; Shinohara, M.

2008-01-01

Purpose: We performed superselective intra-arterial infusion chemotherapy (SIC) according to a protocol in which drug distribution is evaluated by the use of interventional radiology (IVR)-computed tomography (CT) system, and the chemotherapy is combined with medium-dose conformal radiation therapy (CRT). We analyzed retrospectively the factors that affect the midterm survival ratio, including local response, for stage III and IV squamous cell carcinomas of the oral cavity. Materials and methods: Forty consecutive patients with stage III and IV squamous cell carcinomas of the oral cavity and who had undergone both SIC and CRT were enrolled. A microcatheter was placed in the appropriate feeding artery of the tumor and cisplatin (50 mg/body) was infused twice. CRT was administered with a dual-energy (4 and 10 MV) linear accelerator. The total and daily doses delivered were 30 and 2.0 Gy, respectively. Histopathologic effects were classified into five grades: grade 0 or 1 was defined as a poor response, and grade II or higher as a good response. Age, sex, stage, local response to treatment, mode of invasion and lymph node metastasis were analyzed, and differences in the midterm survival ratio were assessed. Results: The 3-year survival ratio of the 40 cases was 67%. A good local response (III or IV) was achieved in 75% of the cases. The survival ratio of the good local response group was significantly better than that of the poor response group (p = 0.04). Mode of invasion (p = 0.03) and lymph node metastasis (p = 0.01) were also predictive of survival. In the multivariable analysis of survival, however, no variables including good local response (p = 0.12), were predictive. Conslusion: Our new protocol improved local response, but it did not contribute to the survival ratio

Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma

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Xu, Qin; Zhang, Zhiyuan; Zhang, Ping; Chen, Wantao

2008-01-01

Antisense oligonucleotides against hTR (As-ODN-hTR) have shown promising results as treatment strategies for various human malignancies. All-trans retinoic acid (ATRA) is a signalling molecule with important roles in differentiation and apoptosis. Biological responses to ATRA are currently used therapeutically in various human cancers. The aim of this study was to evaluate the anti-tumor effects of As-ODN-hTR combined with ATRA in vivo. In situ human oral squamous cell carcinoma (OSCC) models were established by subcutaneous injection of Tca8113 cells. Mice were treated with sense oligonucleotides against hTR(S-ODN-hTR) alone, As-ODN-hTR alone, ATRA alone, As-ODN-hTR plus ATRA, or S-ODN-hTR plus ATRA. Tumor size and weight were assessed in the mice. Telomerase activity was detected by a TRAP assay, apoptotic cells were evaluated with a Tunel assay, the expression of apoptosis-related proteins (Bcl-2 and Bax) was evaluated by immunohistochemistry and ultrastructural morphological changes in the tumor specimen were examined. Both As-ODN-hTR and ATRA can significantly inhibit tumor growth in this OSCC xenograft solid-tumor model, and the combination of the two agents had a synergistic anti-tumorogenic effect. We also demonstrated that this anti-tumor effect correlated with inhibition of telomerase activity. Furthermore, significant increases in the number of apoptotic cells, typical apoptotic morphology and a downregulation of the anti-apoptotic protein, bcl-2 were observed in the treated tissues. The combination of As-ODN-hTR and ATRA has a synergistic anti-tumor effect. This anti-tumor effect can be mainly attributed to apoptosis induced by a decrease in telomerase activity. Bcl-2 plays an important role in this process. Therefore, combining As-ODN-hTR and ATRA may be an approach for the treatment of human oral squamous cell carcinoma

SIPA1 promotes invasion and migration in human oral squamous cell carcinoma by ITGB1 and MMP7

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Takahara, Toshikazu; Kasamatsu, Atsushi; Yamatoji, Masanobu; Iyoda, Manabu; Kasama, Hiroki; Saito, Tomoaki; Takeuchi, Shin; Endo-Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

2017-01-01

Signal-induced proliferation-associated protein 1 (SIPA1) is known to be a GTPase activating protein. Overexpressed SIPA1 is related to metastatic progression in breast and prostate cancers; however, the relevance of SIPA1 in oral squamous cell carcinoma (OSCC) is still unknown. The aim of this study was to examine SIPA1 expression and its functional mechanisms in OSCC. SIPA1 mRNA and protein expressions were analyzed by quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. The expressions of SIPA1 were up-regulated significantly in vitro and in vivo. Moreover, SIPA1 expression was correlated with regional lymph node metastasis. We next assessed the cellular functions associated with tumoral metastasis using SIPA1 knockdown (shSIPA1) cells and analyzed the downstream molecules of SIPA1, i.e., bromodomain containing protein 4(BRD4), integrin beta1 (ITGB1), and matrix metalloproteinase 7 (MMP7). The shSIPA1 cells showed decreased invasiveness and migratory activities, however cellular adhesion ability was maintained at a high level. In addition, ITGB1 expression was greater in shSIPA1 cells, whereas MMP7 expression was lower than in control cells. This research is the first to establish that SIPA1 promotes cancer metastasis by regulating the ITGB1 and MMP7. Therefore, SIPA1 might be a novel therapeutic target for patients with lymph node metastasis of OSCC. - Highlights: • SIPA1 expression was up-regulated in oral squamous cell carcinoma (OSCC). • SIPA1-positive OSCCs were correlated with regional lymph node metastasis. • SIPA1 controlled BRD4 and influenced transcription of ITGB1and MMP7. • SIPA1 induced cellular invasion and migration and decreased cellular adhesion. • SIPA1 might be a potential biomarker of cancer metastasis for OSCC.

SIPA1 promotes invasion and migration in human oral squamous cell carcinoma by ITGB1 and MMP7

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Takahara, Toshikazu [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba (Japan); Kasamatsu, Atsushi, E-mail: kasamatsua@faculty.chiba-u.jp [Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba (Japan); Yamatoji, Masanobu [Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba (Japan); Iyoda, Manabu; Kasama, Hiroki; Saito, Tomoaki [Division of Oral Surgery, Chiba Rosai Hospital, Chiba (Japan); Takeuchi, Shin [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba (Japan); Endo-Sakamoto, Yosuke [Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba (Japan); Shiiba, Masashi [Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan); Tanzawa, Hideki [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba (Japan); Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba (Japan); Uzawa, Katsuhiro, E-mail: uzawak@faculty.chiba-u.jp [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba (Japan); Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba (Japan)

2017-03-15

Signal-induced proliferation-associated protein 1 (SIPA1) is known to be a GTPase activating protein. Overexpressed SIPA1 is related to metastatic progression in breast and prostate cancers; however, the relevance of SIPA1 in oral squamous cell carcinoma (OSCC) is still unknown. The aim of this study was to examine SIPA1 expression and its functional mechanisms in OSCC. SIPA1 mRNA and protein expressions were analyzed by quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. The expressions of SIPA1 were up-regulated significantly in vitro and in vivo. Moreover, SIPA1 expression was correlated with regional lymph node metastasis. We next assessed the cellular functions associated with tumoral metastasis using SIPA1 knockdown (shSIPA1) cells and analyzed the downstream molecules of SIPA1, i.e., bromodomain containing protein 4(BRD4), integrin beta1 (ITGB1), and matrix metalloproteinase 7 (MMP7). The shSIPA1 cells showed decreased invasiveness and migratory activities, however cellular adhesion ability was maintained at a high level. In addition, ITGB1 expression was greater in shSIPA1 cells, whereas MMP7 expression was lower than in control cells. This research is the first to establish that SIPA1 promotes cancer metastasis by regulating the ITGB1 and MMP7. Therefore, SIPA1 might be a novel therapeutic target for patients with lymph node metastasis of OSCC. - Highlights: • SIPA1 expression was up-regulated in oral squamous cell carcinoma (OSCC). • SIPA1-positive OSCCs were correlated with regional lymph node metastasis. • SIPA1 controlled BRD4 and influenced transcription of ITGB1and MMP7. • SIPA1 induced cellular invasion and migration and decreased cellular adhesion. • SIPA1 might be a potential biomarker of cancer metastasis for OSCC.

Lysophosphatidylcholine acyltransferase1 overexpression promotes oral squamous cell carcinoma progression via enhanced biosynthesis of platelet-activating factor.

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Shida-Sakazume, Tomomi; Endo-Sakamoto, Yosuke; Unozawa, Motoharu; Fukumoto, Chonji; Shimada, Ken; Kasamatsu, Atsushi; Ogawara, Katsunori; Yokoe, Hidetaka; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

2015-01-01

The relevance of lysophosphatidylcholine acyltransferase1 (LPCAT1), a cytosolic enzyme in the remodeling pathway of phosphatidylcholine metabolism, in oral squamous cell carcinoma (OSCC) is unknown. We investigated LPCAT1 expression and its functional mechanism in OSCCs. We analyzed LPCAT1 mRNA and protein expression levels in OSCC-derived cell lines. Immunohistochemistry was performed to identify correlations between LPCAT1 expression levels and primary OSCCs clinicopathological status. We established LPCAT1 knockdown models of the OSCC-derived cell lines (SAS, Ca9-22) for functional analysis and examined the association between LPCAT1 expression and the platelet-activating factor (PAF) concentration and PAF-receptor (PAFR) expression. LPCAT1 mRNA and protein were up-regulated significantly (poral keratinocytes. Immunohistochemistry showed significantly (poral cancer.

Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

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Marcinkiewicz, Katarzyna M.; Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu

2014-01-01

To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. - Highlights: • RNAseq elucidates differences between non-tumorigenic and tumorigenic oral keratinocytes. • Changes in HOX mRNA in SCC-9 vs. OKF6-TERT1R cells are a result of altered epigenetic regulation. • RNAseq shows that retinoic acid (RA) influences gene expression in both OKF6-TERT1R and SCC-9 cells.

Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

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Marcinkiewicz, Katarzyna M.; Gudas, Lorraine J.

2014-01-01

To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. - Highlights: • RNAseq elucidates differences between non-tumorigenic and tumorigenic oral keratinocytes. • Changes in HOX mRNA in SCC-9 vs. OKF6-TERT1R cells are a result of altered epigenetic regulation. • RNAseq shows that retinoic acid (RA) influences gene expression in both OKF6-TERT1R and SCC-9 cells

SOX4 expression is associated with treatment failure and chemoradioresistance in oral squamous cell carcinoma

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Yoon, Tae Mi; Kim, Sun-Ae; Cho, Wan Seok; Lee, Dong Hoon; Lee, Joon Kyoo; Park, Young-Lan; Lee, Kyung-Hwa; Lee, Jae Hyuk; Kweon, Sun-Seog; Chung, Ik-Joo; Lim, Sang Chul; Joo, Young-Eun

2015-01-01

In humans, sex-determining region-Y (SRY) related high-mobility-group box 4 (SOX4) is linked to development and tumorigenesis. SOX4 is over-expressed in several cancers and has prognostic significance. This study evaluated whether SOX4 affects oncogenic behavior and chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC) cells, and documented the relationship between its expression and prognosis in oral squamous cell carcinoma (OSCC). We used small interfering RNA in HNSCC cells to evaluate the effect of SOX4 on cell proliferation, apoptosis, chemoradiation-induced apoptosis, invasion, and migration. SOX4 expression in OSCC tissues was investigated by immunohistochemistry. SOX4 knockdown (KO) decreased cell proliferation and induced apoptosis by activating caspases-3 and −7, and poly-ADP ribose polymerase and suppressing X-linked inhibitor of apoptosis protein in HNSCC cells; it also enhanced radiation/cisplatin-induced apoptosis; and suppressed tumor cell invasion and migration. Immunostaining showed SOX4 protein was significantly increased in OSCC tissues compared with adjacent normal mucosa. SOX4 expression was observed in 51.8 % of 85 OSCC tissues, and was significantly correlated with treatment failure (P = 0.032) and shorter overall survival (P = 0.036) in patients with OSCC. SOX4 may contribute to oncogenic phenotypes of HNSCC cells by promoting cell survival and causing chemoradioresistance. It could be a potential prognostic marker for OSCC. The online version of this article (doi:10.1186/s12885-015-1875-8) contains supplementary material, which is available to authorized users

Oral squamous cell carcinoma proliferative phenotype is modulated by proanthocyanidins: a potential prevention and treatment alternative for oral cancer

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Swapp Aaron

2007-06-01

Full Text Available Abstract Background Despite the recently reported drop in the overall death rate from cancer, the estimated survival rate and number of deaths from oral cancer remain virtually unchanged. Early detection efforts, in combination with strategies for prevention and risk-reduction, have the potential to dramatically improve clinical outcomes. The identification of non-toxic, effective treatments, including complementary and alternative therapies, is critical if the survival rate is to be improved. Epidemiologic studies have suggested a protective effect from certain plant-derived foods and extracts; however, it has been difficult to isolate and identify the compounds most responsible for these observations. The primary purpose of this study was to investigate the response of human oral squamous cell carcinoma (OSCC to proanthocyanidin (PAC, a plant-derived compound that may inhibit the progression of several other cancers. Methods Using a series of in vitro assays, we sought to quantify the effects of PAC on OSCC, cervical carcinoma, and non-cancerous cell lines, specifically the effects of PAC on cell proliferation. Recent data suggest that infection with the human papillomavirus (HPV may also modulate the proliferative potential of OSCC; therefore, we also measured the effects of PAC administration on HPV-transfected OSCC proliferation. Results Our results demonstrated that PAC administration was sufficient to significantly suppress cellular proliferation of OSCC in a dose-dependent manner. In addition, the increased proliferation of OSCC after transfection with HPV 16 was reduced by the administration of PAC, as was the proliferation of the cervical cancer and non-cancerous cell lines tested. Our results also provide preliminary evidence that PAC administration may induce apoptosis in cervical and oral cancer cell lines, while acting merely to suppress proliferation of the normal cell line control. Conclusion These results signify that PAC may be

HPV and cancer of the oral cavity.

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Hübbers, Christian U; Akgül, Baki

2015-01-01

Increased awareness of human papillomavirus (HPV) as an etiological cause of head and neck squamous cell carcinoma has increased the interest in analysis of distinct oral sub-sites. It is currently under debate, whether HPV plays a role in the development of squamous cell carcinoma of the oral cavity (OSCC). The weakness in most published studies is the lack of performing different HPV detection tests combined with analysis for biological activity of the virus. In addition, different sub-sites of the oral cavity had been combined to a single entity, which retrospectively leads to a highly heterogeneous basis of data. In this review we mainly discuss the unclear role of HPV in OSCC development.

Oral verrucous carcinoma. Treatment with radiotherapy

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Nair, M.K.; Sankaranarayanan, R.; Padmanabhan, T.K.; Madhu, C.S.

1988-01-01

Fifty-two cases of oral verrucous carcinoma treated with radiotherapy at the Regional Cancer Centre, Trivandrum, Kerala, India in 1982 were evaluated to determine the distribution within the oral cavity, clinical extent, and effectiveness of radiotherapy in controlling the disease. The most common site was the buccal mucosa. Fifty percent of the patients had clinically negative regional lymph nodes and 33% were in earlier stages (T1, T2, N0, and M0). The overall 3-year no evidence of disease (NED) survival rate was 44%. The 3-year NED survival rate with radium implant was 86%. We cannot comment on anaplastic transformation after radiotherapy because our treatment failures have not been subjected for biopsy concerning this matter. Because the results are comparable with those of well-differentiated squamous cell carcinoma, we think that the treatment policies advocated for oral squamous cell carcinoma are also applicable to oral verrucous carcinoma

Treatment of patients with clinically lymph node-negative squamous cell carcinoma of the oral cavity

International Nuclear Information System (INIS)

Jang, Won-II; Wu, Hong-Gyun; Park, Charn-II; Kim, Kwang-Hyun; Sung, Myoung-Whun; Kim, Myung-Jin; Choung, Pill-Hoon; Lee, Jong-Ho; Choi, Jin-Yong

2008-01-01

The objective of this study was to evaluate treatment outcome and to determine optimal treatment strategy for patients with clinically lymph node-negative (N0) oral cavity squamous cell carcinoma (SCC). Two hundred and twenty-seven patients with oral cavity SCC received radiotherapy with curative intent. We retrospectively analyzed 69 patients with clinically N0 disease. Forty-three patients were treated with surgery followed by radiotherapy (S+EBRT) and 26 with radiotherapy alone (EBRT). The median doses administered were 63.0 Gy for S+EBRT and 70.2 Gy for EBRT. The rates of occult metastasis were 60% for T1, 69% for T2, 100% for T3 and 39% for T4, respectively, among patients who underwent neck dissection. A contralateral occult metastasis occurred only in two patients. The median follow-up was 39 months (range, 6-170 months). The 5-year overall survival (OS), disease-free survival (DFS), local control (LC) and regional control (RC) rates for all patients were 56, 50, 66 and 79%, respectively. The 5-year OS, DFS, LC and RC rates were 67/39% (P<0.01), 66/24% (P<0.01), 87/30% (P<0.01) and 73/89% (P=0.11) for S+EBRT/EBRT, respectively. The risk for occult neck metastasis is high in patients with oral cavity SCC; therefore, elective neck treatment should be considered. Excellent RC for subclinical disease can be achieved with radiotherapy alone. However, external beam radiotherapy alone to primary tumor resulted in poor LC and combined treatment with surgery and radiotherapy appeared to be a better treatment strategy. (author)

Phase II Study of Preoperative Concurrent Chemoradiation Therapy With S-1 in Patients With T4 Oral Squamous Cell Carcinoma

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Nomura, Tomoko; Murakami, Ryuji; Toya, Ryo; Teshima, Keiko; Nakahara, Aya; Hirai, Toshinori; Hiraki, Akimitsu; Nakayama, Hideki; Yoshitake, Yoshihiro; Ota, Kazutoshi; Obayashi, Takehisa; Yamashita, Yasuyuki; Oya, Natsuo; Shinohara, Masanori

2010-01-01

Purpose: To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC). Methods and Materials: Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks. Concurrently, S-1 (80 mg/m 2 /day) was administered orally twice daily for 14 consecutive days. Results: We enrolled 46 patients. All underwent radiotherapy as planned; however, oral S-1 was discontinued in 3 patients who manifested acute toxicity. Grade 3 toxicities were mucositis (20%), anorexia (9%), and neutropenia (4%). We encountered no Grade 4 adverse events or serious postoperative morbidity requiring surgical intervention. After CCRT, 32 of the 46 patients underwent radical resection; in 17 (53%) of the operated patients, the pathologic response was complete. During follow-up ranging from 7 to 58 months (median, 22 months), tumor control failed in 5 (16%) of the 32 operated patients; there were 3 local and 2 regional failures. Of the 14 non-operated patients, 8 (57%) manifested local (n = 7) or regional failure (n = 1). The 3-year overall survival rate for all 46 patients was 69%; it was significantly higher for operated than for non-operated patients (82% vs. 48%; p = 0.0288). Conclusion: Preoperative CCRT with S-1 is feasible and effective in patients with T4 oral SCC. Even in inoperable cases, CCRT with S-1 provides adequate tumor control.

[Human papilloma virus and its association with oral cancer].

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Bologna-Molina, Ronell E; Castañeda-Castaneira, Raúl E; Molina-Frechero, Nelly; Pérez-Rodríguez, Eréndira

2006-01-01

Oral cancer it a pathology of multifactorial etiology, where some factors such as age, sex, race, genetic predisposition, nutrition, and the use of tobacco and alcohol have a bearing on. In the last years, some authors showed the implication of the human papilloma virus (HPV) in the development of precarcinogenic lesions and of oral squamous cell carcinoma. The infection by HPV has been associated to hyperplastic epithelial lesions, papilloma and warty carcinoma in skin and in different types of mucosa, including the anus-genital, cervical, urethral, tracheobronchial, nasal, laryngeal and oral mucosa tracts. The viral high-risk geno-types (oncogenic) such as 16, 18, 31, 33 and 35 are frequently associated to leukoplakia and squamous carcinoma. An association of HPV with oral squamous carcinoma in patients that consume tobacco and alcohol has been fundamentally established. It is important to study and to frequently review the role that viral infections and cancer have, and maybe in the future, it would be possible to create a vaccine that diminishes the frequency of oncological problems.

Genetic etiology of oral cancer.

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Ali, Johar; Sabiha, Bibi; Jan, Hanif Ullah; Haider, Syed Adnan; Khan, Abid Ali; Ali, Saima S

2017-07-01

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. It accounts for 2.5% of all new cancer cases and 1.9% of all cancer deaths annually. More than 90% of oral cancers (occurring in the mouth, lip, and tongue) are oral squamous cell carcinoma. The incidence rate of oral cancer varies widely throughout the world, with an evident prevalence in South Asian countries. This high incidence occurs in correlation with oral cancer-associated behaviors such as alcohol, tobacco use. Researchers have reported that these behaviors lead to genetic variations in tumor suppressor genes (APC, p53), proto-oncogenes (Myc), oncogene (Ras) and genes controlling normal cellular processes (EIF3E, GSTM1). Processes such as segregation of chromosomes, genomic copy number, loss of heterozygosity, telomere stabilities, regulations of cell-cycle checkpoints, DNA damage repairs and defects in notch signaling pathways are involved in causing oral cancer. In order to develop preventive and therapeutic options, it is necessary to comprehend the basic molecular mechanisms forcing oral tumorigenesis. This review examines, in detail, the mechanisms of genetic alteration which are considered to be responsible for the initiation of oral cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Incidence of low risk human papillomavirus in oral cancer: a real time PCR study on 278 patients.

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Palmieri, A; Scapoli, L; Martinelli, M; Pezzetti, F; Girardi, A; Spinelli, G; Lucchese, A; Carinci, F

2011-01-01

Squamous cell carcinoma is the most frequent malignant tumour of the oral cavity. It is widely known that tobacco and alcohol consumption are the major causes of the development of oral squamous cell carcinoma (OSCC). The human papilloma virus infection has also been postulated as a risk factor for squamous cell carcinoma, although conflicting results have been reported. The aim of this study is to evaluate the presence of high-risk and low-risk type human papillomavirus in a large sample of squamous cell carcinoma limited to the oral cavity by means of quantitative real-time polymerase chain reaction. Data were obtained from 278 squamous cell carcinoma limited to oral cavity proper. Sequencing revealed that 5 samples were positive for HPV type 16, 5 for HPV type 11, and 1 for HPV type 6. Human papillomavirus 11 was detected in 5 tumours out of the 278 examined. The prevalence rate for Human papillomavirus 11 was 1.8% (C.I. 0.7-3.9). The matched case-controls analysis indicated that the prevalence among controls did not significantly differ with respect to cases and that Human papillomavirus 11 alone did not correlate with squamous cell carcinoma.

The 434(G>C) polymorphism in the eosinophil cationic protein gene and its association with tissue eosinophilia in oral squamous cell carcinomas

DEFF Research Database (Denmark)

Pereira, Michele C; Oliveira, Denise T; Olivieri, Eloísa H R

2010-01-01

OBJECTIVE: The aim of this study was to investigate the prevalence of the Eosinophil cationic protein (ECP)-gene polymorphism 434(G>C) in oral squamous cell carcinoma (OSCC) patients and its association with tumor-associated tissue eosinophilia (TATE), demographic, clinical, and microscopic...... of ECP-gene polymorphism 434(G>C) with TATE, demographic, clinical, and microscopic variables in OSCC patients. Disease-free survival and overall survival were calculated by the Kaplan-Meier product-limit actuarial method and the comparison of the survival curves were performed using log rank test...

Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs.

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Boria, Pedro A; Murry, Daryl J; Bennett, Peter F; Glickman, Nita W; Snyder, Paul W; Merkel, Brenna L; Schlittler, Deborah L; Mutsaers, Anthony J; Thomas, Rose M; Knapp, Deborah W

2004-02-01

To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors. Prospective nonrandomized clinical trial. 25 dogs. Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h). The initial cisplatin dose (50 mg/m2) was increased by 5 mg/m2 until the MTD was reached. Tumor stage and size were determined at 6-week intervals during treatment. The pharmacokinetics of cisplatin were determined in dogs receiving a combination of cisplatin and piroxicam during the clinical trial and dogs that were treated with cisplatin alone. 11 dogs with OMM and 9 dogs with SCC were included in the clinical trial. The MTD of cisplatin when administered in combination with piroxicam was 50 mg/m2. Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM. The most common abnormality observed was renal toxicosis. Clearance of cisplatin in dogs that were treated with cisplatin alone was not significantly different from that in dogs treated with a combination of cisplatin and piroxicam. Cisplatin administered in combination with piroxicam had antitumor activity against OMM and SCC. The level of toxicity was acceptable, although renal function must be monitored carefully.

Assessment of the quality of life of elderly with diagnosis of oral squamous cell carcinoma submitted to combined modality therapy

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Erasmo Bernardo Marinho

2017-06-01

Full Text Available Introduction: Evaluating the quality of life allows a more accurate clinical control as well as the provision of prognostic information for specific groups. This study was designed to evaluate the quality of life of elderly diagnosed with oral squamous cell carcinoma submitted to combined modality therapy. Methods: This is a retrospective and observational study, with cross-sectional quantitative character. A total of 206 records of patients with head and neck cancer treated between April 2013 and October 2014 were analyzed. Eleven patients over six months of treatment completion were included in the study. The questionnaire of quality of life of the University of Washington (UW-QOL was applied. The data were collected regarding the social-demographic, clinical-pathological and therapeutic profiles, and the non-stimulated salivary flow was measured. Statistical analysis of quantitative data was performed by the Spearman nonlinear correlation, considering a confidence of 95%. Results: Chewing, saliva and speech showed the lowest scores (31.8; 42.3; 60.6, respectively. Statistically significant correlation was found between: shoulder and mood (r=0.787; swallowing and chewing (r=0.761; completion time of radiotherapy and recreation (r=0.659; activity and recreation (r=0.653; pain and swallowing (r=0.626; chewing and speech (r=0.607; age and speech (r=-0.617. Conclusions: Elderly with oral squamous cell carcinoma diagnosis sunmitted to combined modality therapy presented the areas related to chewing, saliva and speech as the most committed ones. Older individuals have greater impairment of speech, as well as those with longer completion of radiotherapy have better results related to the recreation area.

Molecular concept in human oral cancer

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Krishna, Akhilesh; Singh, Shraddha; Kumar, Vijay; Pal, U. S.

2015-01-01

The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in...

Impact of mandibular invasion on prognosis in oral squamous cell carcinoma four centimeters or less in size.

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Fives, Cassie; Nae, Andreea; Roche, Phoebe; O'Leary, Gerard; Fitzgerald, Brendan; Feeley, Linda; Sheahan, Patrick

2017-04-01

Previous studies have reported variable results for the impact of bone invasion on survival in oral cancer. It is unclear whether bone invasion in small (≤4 cm) squamous cell carcinomas (SCC) of the oral cavity is an independent adverse prognosticator. Our objective was to investigate impact on survival of bone invasion in SCC of floor of mouth (FOM), lower alveolus (LA), and retromolar trigone (RMT) ≤4 cm in size. Retrospective study of 96 patients with SCC of the FOM, LA, and RMT undergoing primary surgical treatment. Original pathology reports and slides were reviewed by three pathologists. Level of bone invasion was categorized as cortical or medullary. Main outcome measures were local control (LC) and overall survival (OS). Bone invasion was present in 31 cases (32%). On review of pathology slides, all cases of bone invasion demonstrated medullary involvement. Median follow-up was 36 months for all patients, and 53 months for patients not dying from cancer. Among tumors ≤4 cm, bone invasion was associated with significantly worse LC (P =.04) and OS (P =.0005). Medullary invasion (hazard ratio: 2.2, 95% confidence interval: 1.1-4.4, P =.03), postoperative radiotherapy (hazard ratio: 0.3, 95% confidence interval: 0.1-0.5, P oral cancers, irrespective of small size of primary tumor. Such cases should be considered for postoperative radiotherapy. 4. Laryngoscope, 127:849-854, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinomas of the oral floor

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Joos Ulrich

2005-07-01

Full Text Available Abstract Background Hypoxia-inducible factor 1 (HIF-1 is a transcription factor, which plays a central role in biologic processes under hypoxic conditions, especially concerning tumour angiogenesis. HIF-1α is the relevant, oxygen-dependent subunit and its overexpression has been associated with a poor prognosis in a variety of malignant tumours. Therefore, HIF-1α expression in early stage oral carcinomas was evaluated in relation to established clinico-pathological features in order to determine its value as a prognostic marker. Methods 85 patients with histologically proven surgically treated T1/2 squamous cell carcinoma (SCC of the oral floor were eligible for the study. Tumor specimens were investigated by means of tissue micro arrays (TMAs and immunohistochemistry for the expression of HIF-1. Correlations between clinical features and the expression of HIF-1 were evaluated by Kaplan-Meier curves, log-rank tests and multivariate Cox regression analysis. Results HIF-1α was frequently overexpressed in a probably non-hypoxia related fashion. The expression of HIF-1α was related with a significantly improved 5-year survival rate (p Conclusion HIF-1α overexpression is an indicator of favourable prognosis in T1 and T2 SCC of the oral floor. Node negative patients lacking HIF-1α expression may therefore be considered for adjuvant radiotherapy.

Prognostic impact of the level of nodal involvement: retrospective analysis of patients with advanced oral squamous cell carcinoma.

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Murakami, R; Nakayama, H; Semba, A; Hiraki, A; Nagata, M; Kawahara, K; Shiraishi, S; Hirai, T; Uozumi, H; Yamashita, Y

2017-01-01

We retrospectively evaluated the prognostic impact of the level of nodal involvement in patients with advanced oral squamous cell carcinoma (SCC). Between 2005 and 2010, 105 patients with clinical stage III or IV oral SCC had chemoradiotherapy preoperatively. Clinical (cN) and pathological nodal (pN) involvement was primarily at levels Ib and II. We defined nodal involvement at levels Ia and III-V as anterior and inferior extensions, respectively, and recorded such findings as extensive. With respect to pretreatment variables (age, clinical stage, clinical findings of the primary tumour, and nodal findings), univariate analysis showed that extensive cN was the only significant factor for overall survival (hazard ratio [HR], 3.27; 95% CI 1.50 to 7.13; p=0.001). Univariate analysis showed that all pN findings, including the nodal classification (invaded nodes, multiple, and contralateral) and extensive involvement were significant, and multivariate analysis confirmed that extensive pN (HR 4.71; 95% CI 1.85 to 11.97; p=0.001) and multiple pN (HR 2.59; 95% CI 1.10 to 6.09; p=0.029) were independent predictors of overall survival. Assessment based on the level of invaded neck nodes may be a better predictor of survival than the current nodal classification. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Gingival squamous cell carcinoma masquerading as an aphthous ulcer

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Kumari, Prathypaty Santha; Kumar, Gudi Pavan; Bai, Yendluri Durga; Reddy, Eragam Yella Reddy Balaji Naveen

2013-01-01

Gingival squamous cell carcinoma (GSCC) is an uncommon condition of the oral cavity. It is seldom associated with classic risk factors of oral cancer and shows a predilection for females. It's close clinical resemblances to various lesions of the oral cavity may make it go unnoticed. This may lead to diagnosis at advanced stages and coupled with the proximity to underlying alveolar bone may result in subsequent morbidity and mortality. A case of GSCC camouflaged as an aphthous ulcer in a middle aged woman is presented. The article highlights the importance of early diagnosis resulting in conservative treatment approaches. PMID:24174737

HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinomas of the oral floor

International Nuclear Information System (INIS)

Fillies, Thomas; Werkmeister, Richard; Diest, Paul J van; Brandt, Burkhard; Joos, Ulrich; Buerger, Horst

2005-01-01

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions, especially concerning tumour angiogenesis. HIF-1α is the relevant, oxygen-dependent subunit and its overexpression has been associated with a poor prognosis in a variety of malignant tumours. Therefore, HIF-1α expression in early stage oral carcinomas was evaluated in relation to established clinico-pathological features in order to determine its value as a prognostic marker. 85 patients with histologically proven surgically treated T1/2 squamous cell carcinoma (SCC) of the oral floor were eligible for the study. Tumor specimens were investigated by means of tissue micro arrays (TMAs) and immunohistochemistry for the expression of HIF-1. Correlations between clinical features and the expression of HIF-1 were evaluated by Kaplan-Meier curves, log-rank tests and multivariate Cox regression analysis. HIF-1α was frequently overexpressed in a probably non-hypoxia related fashion. The expression of HIF-1α was related with a significantly improved 5-year survival rate (p < 0.01) and a significantly increased disease free period (p = 0.01) independent from nodal status and tumour size. In primary node negative T1/T2 SCC of the oral floor, absence of HIF-1α expression specified a subgroup of high-risk patients (p < 0.05). HIF-1α overexpression is an indicator of favourable prognosis in T1 and T2 SCC of the oral floor. Node negative patients lacking HIF-1α expression may therefore be considered for adjuvant radiotherapy

Squamous cell carcinoma of the oral cavity and oropharynx in patients aged 18-45 years: A case-control study to evaluate the risk factors with emphasis on stress, diet, oral hygiene, and family history.

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Dholam, K P; Chouksey, G C

2016-01-01

Increasing incidence of squamous cell carcinoma (SCC) of the oral cavity and oropharynx is reported in young adults. However, there is a paucity regarding etiology and risk factors. To evaluate the exposure potential carcinogenic factors among a sample aged 45 years and younger, diagnosed with SCC of the oral cavity and oropharynx. Eighty-five case samples aged 18-45 years, diagnosed with SCC of the oral cavity and oropharynx were compared with 85 controls who had never had cancer, matched for age and sex. This study was conducted by questionnaire-based interviews. Questionnaire contained items about exposure to the following risk factors: Caries prevalence, oral hygiene status, dental trauma, dental visit, stress, family history of cancer, environmental exposure to potential carcinogens, diet, body mass index (BMI), habits such as smoking, tobacco chewing, betel quid/pan, or supari. Odds ratios (ORs) of oral and pharyngeal cancer and the corresponding 95% confidence intervals were estimated using multiple logistic regression models. Poral hygiene, stress, dental trauma, low BMI, family history of cancer, exposure to environmental carcinogens, and habit of placement of quid for 11-20 years. An increased risk of oral and pharyngeal cancer was seen in cases who had poor oral hygiene, stress, dental trauma, low BMI, family history of cancer, exposure to environmental carcinogens, and habit of placement of quid.

SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK: NEW AVENUES OF TREATMENT?

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T. Braunschweig

2013-01-01

Full Text Available Squamous cell carcinoma of the head and neck counts for 3 % of all cancers in men and half of this number less in women with a 5-year survival of 61 %. While the number of laryngeal carcinoma is decreasing, carcinoma of the oral cavity related to an infection by the human papilloma virus (HPV, high-risk subtypes is increasing, especially in younger patients. HPV related squamous cell carcinomas show better survival data, especially in regard to recurrence free rates or secondary carcinoma of adjacent locations. Squamous cell carcinomas related to the presence of HPV DNA material is almost exclusively found in carcinoma of the oral cavity and oropharyngeal mucosa. Much less frequently HPV is present in hypopharyngeal carcinomas and even less number of cases of squamous cell carcinoma with proof for HPV in the nasopharynx and larynx. In case of evidence for HPV DNA; most cases are positively tested for subtype 16, followed by subtype 18. As a surrogate immunhistochemical marker, p16 INK4A is stained positive, cytoplasmic and nuclear. In a small study by ourselves, we found a positive correlation in 100 % of p16 INK4A positivity and positive HPV testing. Oral squamous cell carcinoma is more frequently related to HPV in patients below 50 years of age with a prevalence of ca. 20 %. Whilst HPV high-risk positive carcinomas show very few mutations in single signalling molecules of the downstream receptor tyrosin kinase pathways, HPV negative carcinomas show in many cases a chaotic DNA mutation type with typical mutations in tumor suppressor genes, as p53 and CDKN2A. This pattern is often seen in carcinoma types develop from a summation of accidental mutations often caused by toxins (e.g. inhaled cigarette smoke. However, it is discussed and under investigation whether a subset of head and neck squamous cell carcinomasdevelop from so called driver mutations, as are called mutations in critical members of signalling pathways and receptor tyrosin kinases

Loss of RUNX3 expression inhibits bone invasion of oral squamous cell carcinoma.

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Park, Junhee; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Kim, Hyungkeun; Park, Kwang-Kyun; Chung, Won-Yoon

2017-02-07

High recurrence and lower survival rates in patients with oral squamous cell carcinoma (OSCC) are associated with its bone invasion. We identified the oncogenic role of RUNX3 during bone invasion by OSCC. Tumor growth and the generation of osteolytic lesions were significantly inhibited in mice that were subcutaneously inoculated with RUNX3-knockdown human OSCC cells. RUNX3 knockdown enhanced TGF-β-induced growth arrest and inhibited OSCC cell migration and invasion in the absence or presence of transforming growth factor-β (TGF-β), a major growth factor abundant in the bone microenvironment. RUNX3 knockdown induced cell cycle arrest at the G1 and G2 phases and promoted G2 arrest by TGF-β in Ca9.22 OSCC cells. RUNX3 knockdown also inhibited both the basal and TGF-β-induced epithelial-to-mesenchymal transition by increasing E-cadherin expression and suppressing the nuclear translocation of β-catenin. In addition, the expression and TGF-β-mediated induction of parathyroid hormone-related protein (PTHrP), one of key osteolytic factors, was blocked in RUNX3-knockdown OSCC cells. Furthermore, treating human osteoblastic cells with conditioned medium derived from RUNX3-knockdown OSCC cells reduced the receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin ratio compared with treatment with conditioned medium from RUNX3-expressing cells. These findings indicate that RUNX3 expression in OSCC cells contributes to their bone invasion and the resulting osteolysis by inducing their malignant behaviors and production of osteolytic factors. RUNX3 alone or in combination with TGF-β and PTHrP may be a useful predictive biomarker and therapeutic target for bone invasion by oral cancer.

Circadian rhythm characteristics of oral squamous cell carcinoma growth in an orthotopic xenograft model

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Zhao NB

2013-01-01

Full Text Available Ningbo Zhao,* Hong Tang,* Kai Yang, Dan Chen Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China*These authors contributed equally to this workBackground: Recent studies show that circadian rhythm changes are closely related to the occurrence and development of various tumors, such as breast, liver, and prostate. However, there are significant differences in circadian rhythm between different tumors. At present, the circadian rhythm characteristics of oral cancer remain unknown. The purpose of this study is to investigate the circadian rhythm characteristics of the in vivo growth of oral squamous cell carcinoma (OSCC.Materials and methods: Thirty-two nude mice were placed under 12-hour light/12-hour dark cycles. The human OSCC cell line BcaCD885 was inoculated in the cheek of nude mice. After 3 weeks, eight mice were sacrificed at four time points, including 4 hours after light onset (HALO, 10 HALO, 16 HALO, and 22 HALO, during a period of 24 hours. The volume of excised tumors was measured and the proliferative index (PI and apoptotic index (AI of tumor cells were determined by flow cytometry. A cosine analysis method was used to determine whether the tumor volume, PI, and AI obeyed a circadian rhythm.Results: There was a significant circadian rhythm in the tumor volume and PI of OSCC cells. For the tumor volume, there were significant differences between the four time points. The peak and trough values of the tumor volume appeared at 3.23 HALO and 15.23 HALO, whereas the peak and trough values of PI appeared at 6.60 HALO and 18.16 HALO, respectively. However, there was no circadian rhythm in the AI of tumor cells, despite significant differences between the four time points.Conclusion: This study demonstrates, for the first time, that the tumor volume and PI of in vivo growing OSCC undergo circadian rhythms. These results support the assertion that time factor should be