Suchergebnisse

Xiaohua Zhuang,1 Mengmeng Lu2 1Department of Stomatology, Gongli Hospital, The Second Military University, Shanghai, China; 2Department of Oral Surgery, Shanghai Stomatological Hospital, Shanghai, China Purpose: FAM46C is known as a tumor suppressor in multiple myeloma. However, there are few studies about the expression and function of FAM46C in oral squamous cell carcinoma (OSCC), which is one of the most common oral cancers in the world. Methods: mRNA and protein expression level were determined by real time PCR and Western blot, respectively. Cell Counting Kit-8 assay and flow cytometry analysis were used to analyze cell proliferation and apoptosis, respectively. Activity of caspase 3 and caspase 9 was determined using biochemical assays. Results: Our results showed that the OSCC cells overexpressing FAM46C had a relatively slower cell proliferation rate and higher cell apoptosis rate compared with control groups. The results from Western blot showed that the expression levels of cleaved caspase 9 and cleaved caspase 3, which are the active forms of caspase 3 and caspase 9 in FAM46C overexpressed OSCC cells, were higher than in the control cells, while the phosphorylation of ERK1/2 together with its upstream regulators Ras and phosphorylation of MEK1/2 were relatively lower. Additionally, the results also showed that ERK1/2 agonist (EGF) or a caspase 3 inhibitor (Z-DEVD-FMK) inhibited activity of caspase 3 and caspase 9 and cell apoptosis rate. Furthermore, by analyzing FAM46C silencing OSCC cells, we found an increased proliferation rate and a reduced apoptosis rate compared with control cells. And those phenomena could be blocked by U0126, which is an ERK1/2 inhibitor. Conclusion: Overall, our data suggest that FAM46C probably acts as a tumor suppressor gene in OSCC cells and the working mechanism of FAM46C may be involved in the caspases and ERK1/2 pathway. Keywords: OSCC, FAM46C, caspases, ERK1/2

Patients and health care workers require continuing education to promote knowledge of the signs, symptoms, and risk factors for oral cancer. This paper reviews the literature assessing diagnostic tools that are currently available or being developed, in order to assist in the biopsy site selection and subsequent diagnosis of patients at risk for oral cancer. There is a general consensus that oral examination of patients at risk for oral squamous cell carcinoma (SCC) should be conducted on a routine basis. However, there can be false‐positive and false‐negative findings. Toluidine blue has been shown to be useful as an adjunct to the clinical examination when used by experienced clinicians. Exfoliative cytology is not currently used as a routine measure for the evaluation of lesions of the oral mucosa, but further development and the application of biologic markers to cytologic specimens may increase its value. Fluorescent imaging of malignant lesions of the oral mucosa has been shown to be sensitive and specific in animal models but thus far has been reported in only one human trial.The sensitivity and specificity of these techniques when used by general practitioners need to be assessed. Further, none of the above procedures has yet been shown to be a cost‐effective public health measure in screening for oral cancer.

AbstractThis reflection describes a life‐limiting case of oral squamous cell carcinoma (SCC) that required thoughtful management facilitated by an advance care plan (ACP). A 70‐year‐old female was diagnosed with a T4aN2bM0 biopsy‐proven invasive, well‐differentiated keratinizing SCC. Surgical wide‐local excision included teeth #11‐16 with left unilateral neck dissection, levels I‐V. She was rehabilitated with maxillary obturator prosthesis and underwent chemoradiation therapy. Her course was complicated by dysphagia and trismus. She experienced multiple recurrences. At a certain point, negative margins could not be achieved without facial disfigurement. The patient, her husband, and providers decided together that further management would be palliative. Before the additional surgical procedures, she communicated a thorough ACP with her husband and providers who were prepared to facilitate difficult care decisions on her behalf. The patient passed away at home with hospice care at the age of 74. This motivated patient with oral SCC and impactful postmanagement complications appreciated the clarity of an ACP. Her values and goals of care were incorporated with ongoing communication and documentation of this plan, which was instrumental in facilitating her person‐centered care. The providers apply lessons learned here in future practice and education of residents and students.

Shu-Hui Lin,1,2,* Hsin-Kai Wang,3,4,* Kun-Tu Yeh,1,5 Hui-Chun Tai,1,6 Hui-Yi Wang,1 Lan-Ru Huang,2 Chun-Wen Chiu,7 Chia-Min Chung,8,9 Bharath Kumar Velmurugan101Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan; 2Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan; 3Public Health Bureau, Tainan City Government, Tainan, Taiwan; 4Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan; 5School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 6Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 7Department of Emergency Medicine, Changhua Christian Hospital, Changhua, Taiwan; 8Graduate Institute of BioMedical Sciences, China Medical University, Taichung, Taiwan; 9Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan; 10Toxicology and Biomedicine Research Group, Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam*These authors contributed equally to this work Purpose: c-MYC has been noted in many tumor types, but its functional significance and clinical utility in oral squamous cell carcinoma (OSCC) are not well known. Here we studied the expression of c-MYC in correlation to clinical outcome in patients with oral squamous cell carcinoma.Methods: The current study, using immunohistochemical staining, first examined c-MYC expression in OSCC patients and further correlated its expression with clinicopathological parameters.Results: c-MYC was expressed in the majority of OSCC patients (n=133). The c-MYC expression is associated with histological grade (P=0.0205) of patients with oral squamous cell carcinoma. Multivariate Cox regression analysis revealed that TN stage (P0.05). Multiplicative-scale interaction between T stage (III/IV) and low c-MYC expression on mortality risk was identified (P=0.0233). Kaplan–Meier survival analysis demonstrated that oral cancer patients (T III/IV stage) with high c-MYC expression had better survival than those with low and medium c-MYC expression (P=0.0270).Conclusion: Our data indicate that c-MYC is a potential biomarker that can be used as a therapeutic target for treating OSCC patients with T stage (III/IV).Keywords: T stage, c-MYC, OSCC, biomarker, survival

ABSTRACTFanconi Anemia patients are a high risk group for solid and hematologic malignancies. The risk seems to be influenced by age, chronic graft versus host disease and immunosuppressive drug regimens. Reports of oral malignant transformation in Fanconi Anemia after hematopoietic stem cell transplantation (HSCT) are increasing probably because of longer survival rates. This is the report of an 18‐ and her 28‐year old sister who developed a post‐HSCT oral squamous cell carcinoma. There were significant differences regarding time to malignant transformation, marrow donor characteristics and graft versus host disease evolution and treatment. The report reinforce the need for a routine head and neck screening for cancer in this particular syndrome and suggest that familial history should also be considered in Fanconi anemia patients at risk for oral malignancy after HSCT.

Nan Zhang,1,* Lingfang Zeng,2,* Shouyi Wang,3,* Ronghua Wang,4 Rui Yang,5 Zuolin Jin,6 Hong Tao1 1Department of Stomatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xian, Shanxi, 710061, People's Republic of China; 2Department of Pediatric Stomatology, Jinan Stomatological Hospital, Jinan, Shandong, 250000, People's Republic of China; 3Department of Oral and Maxillofacial Surgery, Jinan Stomatological Hospital, Jinan, Shandong, 250000, People's Republic of China; 4Department of Pediatrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xian, Shanxi, 710061, People's Republic of China; 5Department of Dental, Xi 'an Tianrui Institute of Stomatology, Xian, Shanxi, 710061, People's Republic of China; 6Department of Orthodontics, Oral Hospital of the Fourth Military Medical University, Xian, Shanxi, 710032, People's Republic of China*These authors contributed equally to this workCorrespondence: Zuolin JinDepartment of Orthodontics, Oral Hospital of the Fourth Military Medical University, No. 145, Changle Weste Road, Xian, Shanxi, 710032, People's Republic of ChinaEmail kn6119@163.comHong TaoDepartment of Stomatology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 227, Yanta West Road, Xian, Shanxi, 710061, People's Republic of ChinaEmail eu3027@163.comBackground: Oral squamous cell carcinoma (OSCC) is a common cancer especially young people in the world. The long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to be closely associated with the progression of various human cancers. However, the role of FER1L4 in OSCC remains unclear.Methods: The expression level of FER1L4 in OSCC tissues and cancer cell lines was detected by using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay and EdU staining assay. Cell invasion and migration were evaluated by Transwell assay. Cell apoptosis was detected by flow cytometry. Luciferase reporter assay was performed to determine the targeting relationship between FER1L4, miR-133a-5p and Prx1. The protein expression of Prx1 was detected by Western blot. In addition, a xenograft tumor model in vivo was constructed to confirm the function of FER1L4.Results: FERIL4 was significantly upregulated in OSCC tissues and cancer cell lines. Moreover, high level of FER1L4 predicted a poor prognosis of OSCC patients. Silencing of FER1L4 not only significantly inhibited cell growth, invasion, migration and induced apoptosis in SCC-9 and HN4 cells in vitro, but also effectively suppressed the tumorigenesis of OSCC cells in vivo. Knockdown of FER1L4 significantly enhanced the expression of miR-133a-5p by sponging it, and then downregulated Prx1 expression.Conclusion: Our study elucidated a new mechanism of lncRNA FER1L4 that promoting OSCC progression by directly targeting miR-133a-5p/Prx1 axis and provided novel therapeutic targets for OSCC.Keywords: OSCC, lncRNA FER1L4, miR-133a-5p, Prx1, tumorigenesis

"Background/aims: Reliable biomarkers with high specificity and sensitivity and the potential to discriminate precancerous or early lesions from oral cancer improve scientific assessment and early detection. Dysregulated circRNAs play a critical role in the occurrence and progression of malignant biological behaviors of OSCC. The study of potential diagnostic roles of hsa_circ_0064357 and hsa_circ_0064358 in early diagnostic of precancerous lesions such as OLP to OSCC as the most common type of head-and-neck squamous cell carcinoma (HNSCC) was the focus of present research. Methods: The differential expression of hsa_circ_0064357, hsa_circ_0064358, and RAF1 target gene predicted using CircInteractome and Circbase databases between OSCC (n=30), OLP (n=10) tissues and their adjacent normal tissues were evaluated by qRT-PCR. The potential diagnostic value of circRNAs was identified by receiver operating characteristic (ROC) curve analysis. Results: hsa_circ_0064357 and hsa_circ_0064358 were identified to be lowly expressed, while RAF1 was upregulated in OSCC and OLP tissues more than adjacent normal tissues. Low expression of circRNAs was markedly correlated with TNM stages of OSCC patients. ROC analysis revealed AUC of 0.962 and 0.965 for hsa_circ_0064357 and hsa_circ_0064358, respectively, suggesting that circRNAs can serve as novel diagnostic biomarkers for early detection of OSCC. Conclusion: hsa_circ_0064357 and hsa_circ_0064358 might be involved in the progression and metastasis of OSCC and could be used as promising novel biomarkers for early diagnosis and the clinical monitoring of the malignant transformation of OLP into OSCC. Keywords: hsa_circ_0064357, hsa_circ_0064358, OSCC, OLP, RAF1 gene"

AbstractOral cancer is a serious threat to humans worldwide. The frequently diagnosed form of oral cancer is oral squamous cell carcinoma (OSCC). The major etiologies of OSCC are the chemical constituents/carcinogens found in tobacco, areca nut, and alcohol. The sperm‐specific antigen 2 (SSFA2) is a crucial human gene and encodes for a protein that communicates between InsP3Rs and the cytoskeleton, regulating the cellular molecular pathways. This study analyzed the role of SSFA2 in OSCC using a computational approach. First, the evolutionarily conserved attributes of human SSFA2 canonical protein (HSCP) were scrutinized, followed by its comparison with human SSFA2 noncanonical proteins (HSNCPs); in addition, the transcript variants encoding for HSCP and HSNCP were also analyzed for sequence disparities. Molecular docking (iGEMDOCK) was performed for predicting HSCP residues interacting with OSCC carcinogens and OSCC therapeutants. Further, the protein interactome of HSCP was analyzed using Cytoscape. >70% amino acids (AAs) in HSCP were evolutionarily conserved; the AAs in the N‐terminal and C‐terminal regions were more conserved than that in the middle region of the protein. The 12 transcript and protein variants encoded by the human SSFA2 showed substantial differences in their sequences. Additionally, the human SSFA2 protein variants showed disparities in their secondary and tertiary structures. Molecular docking showed favorable interaction of carcinogens and therapeutants with the N‐terminus, middle region, and C‐terminus residues of HSCP, highlighting its strong candidature as the therapeutic target in oral malignancy. The structure and protein interactome analyses of HSCP predicted its diverse functionalities in the cell environment. Also, the sequence and structure heterogeneity present between HSCP and HSNCPs implies their varying functional attributes/roles in normal and/or diseased physiologies.

This study was supported by grants from the Instituto de Salud Carlos III (PI19/01255 to J.C.d.V. and P.L.-F., PI19/00560 to J.M.G.P. and CIBERONC CB16/12/00390 to J.P.R.), the Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Ayudas a Grupos PCTI Principado de Asturias (IDI2018/155 to J.P.R.), Fundación Bancaria Caja de Ahorros de Asturias-IUOPA and the FEDER Funding Program from the European Union.

AbstractFanconi anemia is a rare disorder resulting from defects in genes responsible for DNA damage responses. It is characterized by congenital anomalies, aplastic anemia, and a predisposition to cancer. Currently, hematopoietic stem cell transplant (HSCT) is the only curative treatment available for bone marrow failure; however, HSCT increases oral squamous cell carcinoma (OSCC) risk. Here we report the case of a patient diagnosed with Fanconi anemia in childhood who was treated with HSCT and later diagnosed with multiple OSCCs during a 12‐year follow‐up. Despite multiple surgical interventions and radiotherapy regimens, the patient`s health deteriorated. Management of individuals with Fanconi anemia is challenging and must be provided by a multidisciplinary healthcare team to ensure better staging, treatment planning, and coordination.