Cleft lip with or without cleft palate (CL/P) is considered a multifactorial genetic disorder. Folic acid metabolism has been suggested to underlie the development of CL/P. The gene for the enzyme 5,10-methylentetrahydrofolate reductase ( MTHFR ) contributes to folic acid metabolism, and polymorphisms of this gene at C677T (rs1801133) and A1298C (rs1801131) are reported to alter its enzyme activity and are suggested to be involved in CL/P development. We investigated C677T and A1298C polymorphisms of the MTHFR gene in Japanese patients with nonsyndromic CL/P and cleft palate only (CPO). We examined 240 patients with CL/P, 103 fathers and 153 mothers of the patients, and 68 healthy controls. Restriction fragment length polymorphisms (RFLPs) of C677T and A1298C of MTHFR were analyzed. We determined the frequencies of the polymorphisms in the patients and controls and performed a transmission equilibrium test and haplotype analysis of both MTHFR C677T and A1298C. There were no significant differences in the frequencies of MTHFR C677T and A1298C polymorphisms between the patients and controls. We did not observe transmission equilibrium or linkage equilibrium among the cases. In this experimental condition, we did not detect an association of MTHFR C677T and/or A1298C polymorphisms with the development of CL/P in this Japanese cohort.
Cervical lymph node metastasis is an important prognostic factor in oral squamous cell carcinoma (OSCC) , and preoperative evaluation of cervical lymph nodes requires high diagnostic accuracy. We investigated the usefulness of FDG-PET/contrast-enhanced CT for diagnosing cervical lymph node metastasis in OSCC and determined which procedures could be additionally performed to improve diagnostic accuracy. Between April 2005 and March 2013, a total of 115 patients with OSCC who were treated in the Department of Oral and Maxillofacial Surgery, Dokkyo Medical University Hospital participated in this study. The primary sites of OSCC were the tongue (n = 66) , mandibular gingiva (n = 27) , maxillary gingiva (n = 10) , floor of the mouth (n = 6) , and buccal mucosa (n = 6) . The clinical stage of the disease was stage I in 10 cases, stage II in 35 cases, stage III in 17 cases, and stage IV in 53 cases. Uptake of FDG was elevated in the cervical lymph nodes of 48 patients, among whom 45 had cervical metastasis (true-positive) and three did not (false-positive) . Among 67 patients who did not have elevated FDG uptake, 8 patients had cervical metastasis (false-negative)and 59 patients did not (true-negative) . The sensitivity, specificity, and accuracy of FDG-PET at a threshold SUVmax of 2.0 were 84.9%, 95.2%, and 90.4%, respectively. A re-evaluation of patients with negative FDG-PET/contrast-enhanced CT findings together with palpation and MRI increased the diagnostic performance to 93.6%, the sensitivity to 94.5%, and the specificity to 94.1% accuracy. In conclusion, FDG -PE T/contrast-enhanced C T was veryuseful for diagnosing cervical lymph node metastasis in OSCC. Furthermore, palpation and MRI combined with FDG-PET/contrast-enhanced CT is recommended to reduce the rate of false-negative findings. : FDG-PET/contrast-enhanced CT (FDG-PET/ 造影 CT) ,oral squamous cell carcinoma (口腔扁平上皮癌) , cervical lymph node metastasis (頸部リンパ節転移) 1) 獨協医科大学医学部口腔外科学講座 (主任:川又 均教授) 2) 佐野厚生総合病院歯科口腔外科 (主任:和久井崇大部長) 3) 菅間記念病院歯科口腔外科 (主任:齋藤正浩医長) 1)
We have previously demonstrated that stromal cell-derived factor (SDF)-1/CXCR4 system enhances the metastases of oral cancer cells via induction of metabotropic glutamate receptor (mGluR) 5. However, the mechanism(s) of mGluR5 expression induced by the SDF-1/CXCR4 system are largely unknown. Recently, small non-coding RNAs, microRNAs (miRNAs) are involved in the metastatic process of several types of cancers. In this study, we examined the miRNA association involved in the mGluR5 expression using oral cancer cells, B88, which express functional CXCR4 and exhibit highly metastatic potentials. We examined the metastasis-related miRNAs in SDF-1 stimulated B88 cells by use of a miRNA microarray analysis. Consequently, we isolated miR-30 family which has predictive binding sites in 3’-UTR of mGluR5 mRNA in silico analysis. Among these miRNAs, we confirmed the downregulation of all miR-30 family in SDF-1 stimulated B88 cells by the real-time PCR analysis. Next, we transfected these miR-30 families in SDF-1 stimulated B88 cells. We confirmed the downregulation of mGluR5 by the miR-30a-5p and miR-30c-5p overexpression. These results indicated that SDF-1/CXCR4 system might regulate the metastases of oral cancer by the upregulation of mGluR5 via downregulation of miR-30 family. Citation Format: Nobuyuki Kuribayashi, Daisuke Uchida, Makoto Kinouchi, Chikako Koshiji, Sayaka Izumi, Kembun Hakata, Yuske Komiyama, Shuji Tsuchida, Tomonori Hasegawa, Hitoshi Kawamata. Regulation of metabotropic glutamate receptor 5 expression by the miR-30 downregulation induced by the SDF-1/CXCR4 system in oral cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1925.
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