Myiasis Associated with Oral Squamous Cell Carcinoma - A Literature Review

Advanced oral squamous cell carcinoma (SCC) is a possible risk factor for myiasis, a parasitic infestationof vital tissue of humans or other mammals by dipterous larvae (maggots). Oral myiasis is a rare entity, andis mostly associated with various medical and anatomical conditions, such as neglected mandibular fracture,lip incompetence, cerebral palsy, poor oral hygiene, suppurative lesions, and cancerous wounds. Larvae causeitching and irritation due to their crawling movements and can destroy vital tissues, inducing serious or evenlife-threating hemorrhage. The aim of the present article was to highlight the occurrence of oral myiasis inassociation with squamous cell carcinoma and also to highlight the treatment and preventive approaches forsuch cases. A literature search was performed using MEDLINE for articles published in English relating to theoccurrence of oral myiasis in oral SCC. Our search revealed 6 reports on myiasis associated with oral SCC. Thesurgical debridement of infected tissue with the removal of maggots is the treatment of choice in most cases oforal myiasis.     

人口腔鳞状细胞癌组织中N-Cadherin蛋白的表达及临床意义

目的 探讨神经型钙黏附蛋白(N-cadherin)在人口腔鳞状细胞癌(OSCC)组织中的表达及其临床意义.方法 采用免疫组织化学方法 分别检测85例正常口腔上皮组织、62例癌旁不典型增生组织及85例OSCC组织中N-cadherin蛋白的表达,并分析其与临床病理学参数之间的关系.结果 N-cadhedn蛋白在OSCC组...     

Detection of Human Papillomavirus in Oral Squamous Cell Carcinoma,Leukoplakia and Lichen Planus in Thai Patients

Although tobacco, alcohol abuse and betel nut chewing habit are well recognized risk factors for oral squamouscell carcinoma (OSCC), there is evidence to indicate that human papillomavirus (HPV) may also play someinducing role. The purpose of this study was to investigate the presence of HPV in Thai patients with oralsquamous cell carcinoma, leukoplakia and lichen planus using the polymerase chain reaction (PCR). Biopsies oforal squamous cell carcinoma, leukoplakia and lichen planus were obtained from 65 patients, 15 males and 50females, aged between 30-88 years old. Extracted DNA was evaluated for HPV infections by PCR analysis usingconsensus primers specific for L1 region of HPV. Only one sample (1.54%) was positive, suggesting that HPVmay not play an important role in this group of Thai patients.     

Survival Analysis of Oral Squamous Cell Carcinoma in a Subgroup of Young Patients

Oral squamous cell carcinoma (OSCC) is predominantly a disease of middle-aged men with long-termexposure to tobacco and alcohol. An increasing trend has been reported at a younger age worldwide. Clinicalrecords of 100 patients under the age of 45 years treated specifically for oral cavity SCC in our hospital duringa 10-year period were retrospectively analyzed to calculate the survival rates. An obvious male predominancecoincided with smoking trend among Chinese young individuals and female patients were more likely to have notraditional risk factors such as smoking or drinking. The 5-year overall survival rate and disease-free survival ratewere 61.0% and 75.5%, respectively, consistent with other published series over the decade showing a relativelybetter survival among the young. No significant differences clearly correlated with outcome when comparingnon-smokers non-drinkers to ever-smokers and ever drinkers (P>0.05). Overall survival rate and disease freesurvival rate was found to be significantly higher in patients with early-stage disease than with advanced stagedisease (P=0.001, P=0.009 respectively). The strong influence of clinical stage on prognosis emphasizes theimportance of early diagnosis and treatment of oral malignancies for this unique clinical subgroup.     

口腔癌下颌骨边缘切除的临床应用

[目的]对口腔癌的下颌骨边缘切除的效果进行评价。[方法]对248例行下颌骨切除的口腔癌病人的临床资料进行了回顾性研究 ,其中82例行边缘性切除 ,166例行骨段切除 ,比较两组病人的复发率和生存率。[结果]边缘切除和骨段切除两组病人的局部复发率分别为15 6 %和16 3 % ,5年生存率分别为52 2 %和55 7 % ,无显著性差异。[结论]下颌骨边缘切除对于无明显破坏或仅有轻度下颌骨破坏的口腔癌是一种有效的下颌骨处理方法 ,既能取得良好的局部控制效果又能较好地保存病人的口腔功能。     

Anti-Cancer Effects of Traditional Medicinal Herbs on Oral Squamous Cell Carcinoma

Backgrounds: Oral squamous cell carcinoma (OSCC) is among the most frequent oral cancers in individuals under 40. Documents have endorsed that a diet enriched with fruit and vegetables can banish the risk of developing major cancers. This study aimed to evaluate the effects of different concentrations of four medicinal herbs including saffron, ginger, cinnamon and curcumin on OSCC cell line. Methods: Having obtained the aqueous extract of the four herbs, they were administered on OSCC cell lines per se and in dual, triple, and quadruple combinations. Their effects were measured in different concentrations and in 24 and 48 hours by using MTT assay. Results: The minimum and maximum effective concentrations were respectively 108 and 217 mg/ml for curcumin with IC30 of 77mg/ml, 108 and 270 mg/ml for ginger with IC30 of 58 mg/ml, 2 and 10 mg/ml for saffron with IC30 of 1.9 mg/ml, and 5 and 40 mg/ml for cinnamon with IC30 of 3.3 mg/ml. The best effect of the combinations was seen for cinnamon-saffron after both 24 and 48 hours and the four herbs combination after 48 hours. Conclusion: Although all the four herbs were effective on OSCC cell line, the strongest extract was saffron, followed by cinnamon. Combination of cinnamon-saffron and combination of the four herbs showed maximum effects. These findings suggest that traditional medicinal herbs may potentially contribute to oral cancer treatment; providing new windows for the development of new therapeutic strategies for OSCC.     

Expression of Matrix Metalloproteinase-10 at Invasive Front of Squamous Cell Carcinoma and Verrucous Carcinoma in the Oral Cavity

Background: Matrix metalloproteinases (MMPs) are a family of zinc metalloproteinases capable of degradingcomponents of connective tissues. MMP-10 is frequently expressed in human cancers. The aim of this studywas to immunohistochemically evaluate its expression in oral squamous cell carcinoma (OSCC) and verrucouscarcinoma (OVC). Materials and Methods: A retrospective analysis of 73 samples (31 OSCC, 22 OVC and 20non-neoplastic epithelium) was performed. All samples were immunohistochemically stained with monoclonalMMP-10 antibody and expression levels and staining intensity were evaluated with respect to microscopicfeatures. Data were analyzed by SPSS (V.21), Mann-Whitney and Kruskal Wallis tests. Results: MMP-10 wasdetected in all OSCC and OVC cases. The expression of MMP-10 in OSCC was intensive (score 3) and in OVCwas low and moderate (score 1 and score 2) more frequently. Non- neoplastic epithelium did not show MMP-10expression. Differences between groups was statistically significant (p<0.05). However, the expression of MMP-10 was not obviously different between various grades of OSCC. Conclusions: According to our study, MMP-10protein can be important possible factor in the transformation of normal oral epithelium to OVC and OSCC,also the level of MMP-10 expression at invasion front of the lesions can be helpful in the differentiation of OVCand OSCC.     

Rho GTPases are Involved on Regulation of Cytodifferentiation of SCC-4 Oral Squamous Cell Carcinoma Cell Line: A Preliminary Study

Objective: This study evaluated the involvement of Rho GTPases proteins in the regulation of cytodifferentiation of the SCC-4 human oral squamous cell carcinoma cell line. Methods: Cytokeratin and vimentin immunofluorescence and F-actin staining, assays were performed with control cells and Clostridium difficile 1, 2 and 4 μg/mL Toxin A (Rho GTPases inhibitor) treated SCC-4 cells on three-dimensional MatrigelTM for 24 h. Samples were analyzed by using confocal laser microscopy. Significances were p     

Mining Proteins Associated with Oral Squamous Cell Carcinoma in Complex Networks

The purpose of this study was to construct a protein-protein interaction (PPI) network related to oralsquamous cell carcinoma (OSCC). Each protein was ranked and those most associated with OSCC were minedwithin the network. First, OSCC-related genes were retrieved from the Online Mendelian Inheritance in Man(OMIM) database. Then they were mapped to their protein identifiers and a seed set of proteins was built. Theseed proteins were expanded using the nearest neighbor expansion method to construct a PPI network throughthe Online Predicated Human Interaction Database (OPHID). The network was verified to be statisticallysignificant, the score of each protein was evaluated by algorithm, then the OSCC-related proteins were ranked.38 OSCC related seed proteins were expanded to 750 protein pairs. A protein-protein interaction nerwork wasthen constructed and the 30 top-ranked proteins listed. The four highest-scoring seed proteins were SMAD4,CTNNB1, HRAS, NOTCH1, and four non-seed proteins P53, EP300, SMAD3, SRC were mined using the nearestneighbor expansion method. The methods shown here may facilitate the discovery of important OSCC proteinsand guide medical researchers in further pertinent studies.     

Screening of Differential Promoter Hypermethylated Genes in Primary Oral Squamous Cell Carcinoma

Background: Promoter hypermethylation leads to altered gene functions and may result in malignantcellular transformation. Thus, identification of biomarkers for hypermethylated genes could be useful fordiagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC). Objectives: To screenhypermethylated genes with a microarray approach and to validate selected hypermethylated genes with themethylation-specific polymerase chain reaction (MSPCR). Materials and Methods: Genome-wide analysis ofnormal oral mucosa and OSCC tissues was conducted using the Illumina methylation microarray. The specifieddifferential genes were selected and hypermethylation status was further verified with an independent cohortsample of OSCC samples. Candidate genes were screened using microarray assay and run by MSPCR analysis.Results: TP73, PIK3R5, and CELSR3 demonstrated high percentages of differential hypermethylation status.Conclusions: Our microarray screening and MSPCR approaches revealed that the signature candidates ofdifferentially hypermethylated genes may possibly become potential biomarkers which would be useful fordiagnostic, prognostic and therapeutic targets of OSCC in the near future.     

术中一次性动脉内化疗对口腔鳞癌作用的形态学观察

目的 探讨术中动脉化疗对癌细胞的杀伤机理。方法 对１１例原发的舌、口底鳞癌患者术中行舌动脉内氮芥一次性动脉化疗、随机抽取６例患者的化疗前后肿瘤组织标本进行光及电镜比较。结果 不下用药前后癌细胞形态学无明显差异,电镜观察下见用药后癌细胞细胞间隙增闰半桥粒消失、胞浆疏松、线粒体空泡样变、核固缩等表现。结论术中一次性动脉内化疗在短期内即能对癌细胞超微结构有破坏,其抗癌作用直接迅速。     

Human Papilloma Virus 18 Detection in Oral Squamous Cell Carcinoma and Potentially Malignant Lesions Using Saliva Samples

Background: Oral cancer has become one of the most prevalent cancers worldwide and human Papillomavirusis one of the risk factors for developing oral cancer. For this study HPV18 was chosen as it is one of the high riskHPV types and may lead to carcinogenesis. However, prevalence of HPV18 infection in Oral Squamous CellCarcinoma in Malaysia remains unclear. Objective: This study aimed to investigate the viral load of HPV18DNA in OSCC and potentially malignant lesions using saliva samples. Materials and Methods: Genomic DNAsof thirty saliva samples of normal subjects and thirty saliva samples compromised of 16 samples from potentiallymalignant lesions and 14 of OSCC patients were amplified for HPV18 DNA using a nested polymerase chainreaction analysis. All PCR products were then analyzed using the Bioanalyzer to confirm presence of HPV18DNA. Result: From thirty patients examined, only one of 30 (3.3%) cases was found to be positive for HPV18in this study. Conclusion: The finding of this study revealed that there is a low viral detection of HPV18 inMalaysian OSCC by using saliva samples, suggesting that prevalence of HPV18 may not be important in thisgroup of Malaysian OSCC.     

Integrated Bioinformatics Analysis of mRNAs and miRNAs Identified Potential Biomarkers of Oral Squamous Cell Carcinoma

Background: Oral cancer is a frequently encountered neoplasm of the head and neck region, being the eighth most common type of human malignancy worldwide. Despite improvement in its control, morbidity and mortality, rates have improved little in the past decades. The present investigations about gene interaction and pathways still could not clear the appearance and development of oral squamous cell carcinoma (OSCC), completely. The aim of this study is to investigate the key genes and microRNAs interaction in OSCC. Materials and Methods: The microarray datasets GSE13601 and GSE98463, including mRNA and miRNA profiles, were extracted from the GEO database and were analyzed using GEO2R. Functional and pathway enrichment analyses were performed by using the DAVID database. The protein–protein interaction (PPI) network was constructed and analyzed using STRING database and Cytoscape software, respectively. Finally, miRDB was applied to predict the targets of the differentially expressed miRNAs (DEMs). Results: Totally, 97 differentially expressed genes (DEGs) were found in OSCC, including 66 up-regulated and 31 down-regulated genes. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that up-regulated genes were significantly enriched in movement of cell or subcellular component, cell adhesion, biological adhesion, cellular localization, apoptotic signaling pathway, while the down-regulated genes were enriched in muscle system process and oxidation-reduction process. From the PPI network, the top 10 nodes with the highest degree were detected as hub genes. In addition, 18 DEMs were screened, which included 7 up-regulated and 11 down-regulated miRNAs. STAT1 was potentially targeted by three miRNAs, including has-miR-6825-5P, has-miR-4495, and has-miR-5580-3P. Conclusion: The roles of DEMs such as hsa-mir-5580-3p in OSCC through interactions with DEGs CD44, ACLY, ACTR3, STAT1, LAMC2 and YWHAZ may offer a suitable candidate biomarker pattern for diagnosis, prognosis and treatment processes in OSCC.     

Immunohistochemical Evaluation of GLUT-3 and GLUT-4 in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

Objectives: To evaluate immunohistochemically the expression of GLUT-3 and GLUT-4 in oral epithelial dysplasia(OED) and the oral squamous cell carcinoma (OSCC) and assess possible involvement in the malignant transformation oforal lesions. Methods: Tissue samples of 15 cases of OSCC and 15 of OED were subjected to immunohistochemistrywith anti-GLUT-3 and anti-GLUT-4 antibodies. Five fields of each case were analyzed, to provide percentages ofpositive cells at 400X magnification. Result: GLUT-3 and GLUT-4 were positive in 100% of the analyzed samples,the percentage immunolabeling for GLUT-3 ranging from 19% to 73% in the OED group and 10% to 89% in the OSCCgroup. Positive immunolabeling for GLUT-4 ranged from 15.2% to 79.9% in the OSCC group and 27.1% to 92.6% inthe OED group. Statistical analysis with the Mann-Whitney test revealed that there was a higher expression of GLUT-4 inthe OED group than in the OSCC group (p=0.04) without any significant difference in the GLUT-3 expression (p=0.852).Conclusion: GLUT-4 expression may indicate some role in oncogenic mechanisms which can determine a malignantphenotype. Thus, it is suggested that further studies on the role of GLUT-3 in oral carcinogenesis be conducted.     

Individual and Integrated Effects of Potential Risk Factors for Oral Squamous Cell Carcinoma: A Hospital-Based Case- Control Study in Jazan,Saudi Arabia

Background: Oral cancer is the sixth most common cancer in the world, with a high prevalence reported in Jazanprovince of Saudi Arabia. The objectives of this study were to check individual and integrated effects of potential riskfactors for oral squamous cell carcinoma. Materials and methods: A case control study was designed with a sampleof 210 subjects, in which histopathologically confirmed incident cases (n=70) and controls (n=140) matched for age,gender and referral route, were recruited. Differences in exposure to potential risk factors between cases and controlswere assessed using chi-square and McNemar analyses. A logistic regression model with interactions was applied to checkindividual and integrated effects. Results: Mean age of the sample was 55 years (+ 20 years). Shammah (O.R = 33.01;C.I = 3.22 – 39.88), shisha (O.R = 3.96; C.I = 0.24 – 63.38), and cigarette (O.R = 1.58; C.I = 0.13, 2.50) consumptionwas significantly associated (P<0.05) with oral squamous cell carcinoma development. In contrast, Khat chewing (O.R= 0.67; C.I = 0.19-2.36) was without significant effect. An increase in odds ratios was observed when combinationsof shammah and shisha (O.R = 35.03; C.I = 11.50-65.66), shisha and cigarettes (O.R = 10.52; C.I = 1.03 – 33.90) orshamma and cigarettes (O.R = 10.10; C.I = 0.50 - 20.40) were used. Conclusion: Combined exposure to risk-factorshas serious implications and policies on oral cancer prevention should be designed with attention to this aspect.     

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

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.     

Wnt Signaling: A Potential Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Cellular maintenance and development are two fundamental mechanisms regulated by the canonical Wnt signalingpathway. Wnt/beta-catenin signaling pathway controls a myriad of cellular processes that are essential for normal cellfunctioning. Cell cycle progression, differentiation, fate determination, and migration are generally orchestrated bycanonical Wnt signaling. Altered Wnt/beta-catenin signaling has been considered a promoting event for different typesof cancers and the oncogenic potential of Wnt signaling have been discussed in many cancer types, including breast,colon, pancreatic as well as head and neck. Furthermore, Wnt signaling is critical for the maintenance and stemnessof both the normal as well as cancer stem cells. This review sheds new light on Wnt signaling and explains how it canregulate normal physiological processes and curtail the development of cancer. It depicts the vital functions of Wntsignaling in the stem cell growth and differentiation by focusing on current druggable targets that have been ascribedby recent studies. Thus, Wnt signaling pathway retains a tremendous potential in eradicating head and neck squamouscell carcinoma.     

Increased Expression of the PRL-3 Gene in Human Oral Squamous Cell Carcinoma and Dysplasia Tissues

Phosphatase of regenerating liver (PRL) belongs to a class of the protein tyrosine phosphatase family, whichis known so far to consist of 3 members, PRL-1, PRL-2, and PRL-3. The aim of this study was to uncover therole of PRL genes in development of oral malignancy. We analyzed expression levels of the 3 PRL genes in 50human oral squamous cell carcinomas (OSCCs), 11 dysplasia and 12 normal mucosa tissues by a real-time RTPCRmethod. PRL-3 but not PRL-1 or PRL-2 expressions were significantly higher in OSCC and dysplasia thanin normal mucosa tissues. Additionally, PRL-3 expressions were significantly higher in OSCC tissues harboringdominant-negative p53 or recessive p53 mutation than in those harboring wild-type p53. These results suggestthat PRL-3 plays a role in oral cancer development and can be useful as a marker of pre-malignant and malignantlesion of oral mucosa.     

EZB-ICR Cell Line: A New Established and Characterized Oral Squamous Cell Carcinoma Cell Line From Tongue

Background: Tongue cancer is one of the most aggressive forms of oral squamous cell carcinoma which needs more investigations. Herein, we aimed to establish and characterize a tongue cancer cell line. Methods: Tumor tissue was obtained from a 70-year-old woman with tongue cancer. The established cell line named as EZB-ICR and characterized for doubling time, expression of specific markers, HPV corporation and migration status using flow cytometry, immunofluorescence staining, multiplex PCR, and migration assay. Results: EZB-ICR was negative for expression of mesenchymal specific markers, cytokeratin19, pan-cytokeratin, vimentin and EPCAM, but was positive for S100 and Nestin. No appearance of human papilloma virus DNA was seen. The doubling time of EZB-ICR was 31 hours and migration assay confirmed its metastatic nature. Conclusion: To the best of our knowledge, EZB-ICR is the first tongue human cancer cell line established in Iran, and its features make it appropriate for cancer-based in vitro studies and contribute to more studies on tongue cancer.