Expression of YT Domain Family Protein in Oral Squamous Cell Carcinoma and Its Correlation with the Prognosis.

Background: Proteins contained in the conserved YTH521-b homologous (YTH) domain, have m6A-dependent RNA binding activity. As an important part of YTH domain family proteins, YTHDF1 and YTHDF3 were shown to be associated with many cancers. This paper aimed to reveal the relationship between the expression of these two proteins and the clinical prognosis of OSCC, providing certain guidance for clinical treatment of OSCC. Methods: We detected the expression of YTHDF1 and YTHDF3 in 120 OSCC patients by immunohistochemical analysis. Statistical analysis was used to determine whether the high or low expression of these two genes was significantly associated with age, gender, histological type, clinical stage, or lymph node metastasis. The correlation curve and survival curve of the two genes were produced to evaluate the potential clinical significance. Results: We find the expression of YTHDF1 and YTHDF3 was increased in OSCC tissues compared to adjacent normal tissues. The statistical analysis showed that the expression of YTHDF1 and YTHDF3 was significantly associated with the clinical stage and histological type in OSCC patients. There was also a significant correlation between the expression of YTHDF1 and YTHDF3. A high expression of YTHDF1 and YTHDF3 was related to poor patient prognosis. Conclusion: Our findings suggest that a high expression of YTHDF1 and YTHDF3 may be related to poor patient prognosis.

Upregulation of XRN2 acts as an oncogene in oral squamous cell carcinoma and correlates with poor prognosis.

BACKGROUD: The 5'-3' exoribonuclease 2 (XRN2) has been reported involved in several tumors. However, the clinical significance and molecular mechanism of XRN2 in oral squamous cell carcinoma (OSCC) have not been elucidated. MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to investigate the expression of XRN2 in OSCC and adjacent noncancerous tissues, which was further identified by western blot and GEPIA2 database analysis. Moreover, the relationship between XRN2 expression and the clinicopathological characteristics and prognosis of OSCC patients was evaluated. In addition, in vitro, the effects of XRN2 on OSCC cells were evaluated by Cell Counting Kit-8 (CCK8) assay, colony formation assay, apoptosis assay, wound healing assay, and transwell assays. RESULTS: XRN2 was overexpressed in 44 of 77 (57.1 %) OSCC tissues. High expression of XRN2 was significantly associated with tumor differentiation (P=0.003), pathological clinical stage (P=0.045), lymph node metastasis (P=0.041), and poor overall survival (P=0.0013). Furthermore, the multivariate analysis suggested that XRN2 expression(P=0.002) was determined as an independent prognostic factor for patients with OSCC. Additionally, with functional assays in vitro, we found that downregulation of XRN2 inhibited cell proliferation, migration, and invasion, while promoted apoptosis of OSCC cells. Furthermore, knockdown of XRN2 in OSCC cells could increase the expression of E-cadherin but reduce the expression of Vimentin, which changes the characteristic of epithelial-mesenchymal transition (EMT). CONCLUSION: XRN2 is significantly overexpressed in OSCC tissues and its upregulation was closely associated with poor prognosis of OSCC patients. XRN2 could be a useful prognostic biomarker and a potential therapeutic target for OSCC.

Chronic atrophic gastritis and Helicobacter pylori infection status in liver transplant recipients.

AIM: To investigate the abnormalities of the upper gastrointestinal tract in liver transplant (LT) recipients, especially the prevalence of Helicobacter pylori infection and the incidence of chronic atrophic gastritis (CAG), and to explore the efficacy and safety of H pylori eradication treatment. METHODS: Endoscopic screening was performed prospectively on LT recipients who received regular follow-up in our center. A group of healthy subjects with same age and sex was selected as a control group at a ratio of 1:3 with propensity score matching. All H pylori-positive recipients received Bismuth-containing quadruple therapy (esomeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + bismuth 220 mg, all of the medicines were applied twice daily, for 14 days). RESULT: The prevalence of H pylori infection was significantly lower in LT group than control group [12/102 (11.8%) vs 98/306 (32.0%), P < .001], whereas the prevalence of CAG was similar between the two groups [48/102 (47.1%) vs 138/306 (45.1%), P = .731]. Meanwhile, the incidence of reflux esophagitis [18/102 (17.6%) vs 31/306 (10.1%), P = .043] and bile regurgitation [19/102 (18.6%) vs 30/306 (9.8%), P = .018] were higher in LT group. No correlation between the incidence of upper gastroduodenal abnormalities and postoperative time after liver transplantation was found. The success rate of H pylori eradication therapy was 100% (10/10). The blood concentration of immunosuppressants was 1.7-3.6 times above baseline values during H pylori eradication therapy; however, no severe adverse effects were observed during the proceed with dose adjustments of the immunosuppressants. CONCLUSION: Although the prevalence of H pylori infection was lower in LT recipients than in control subjects, the prevalence of CAG was like that of the general population. H pylori eradication therapy was safe and effective after liver transplantation in our preliminary study.

CircCDR1as upregulates autophagy under hypoxia to promote tumor cell survival via AKT/ERK½/mTOR signaling pathways in oral squamous cell carcinomas.

Autophagy, as an important non-selective degradation mechanism, could promote tumor initiation and progression by maintaining cellular homeostasis and the cell metabolism as well as cell viability. CircCDR1as has been shown to function as an oncogene in cancer progression, however, it remains largely unknown as to how autophagy is regulated by circCDR1as in oral squamous cell carcinoma (OSCC). In this study, we validated the functional roles of circCDR1as in regulation of autophagy in OSCC cells and further investigated how circCDR1as contributed to cell survival via up-regulating autophagy under a hypoxic microenvironment by using combination of human tissue model, in vitro cell experiments and in vivo mice model. We found that hypoxia promoted the expression level of circCDR1as in OSCC cells and elevated autophagy. In addition, circCDR1as further increased hypoxia-mediated autophagy by targeting multiple key regulators of autophagy. We revealed that circCDR1as enhanced autophagy in OSCC cells via inhibition of rapamycin (mTOR) activity and upregulation of AKT and ERK½ pathways. Overexpression of circCDR1as enhanced OSCC cells viability, endoplasmic reticulum (ER) stress, and inhibited cell apoptosis under a hypoxic microenvironment. Moreover, circCDR1as promoted autophagy in OSCC cells by sponging miR-671-5p. Collectively, these results revealed that high expression of circCDR1as enhanced the viability of OSCC cells under a hypoxic microenvironment by promoting autophagy, suggesting a novel treatment strategy involving circCDR1as and the inhibition of autophagy in OSCC cells.

[Optimal design by customized plate on reconstruction of maxillary unilateral defect via free fibula flap].

PURPOSE: To optimize reconstruction of maxillary unilateral defect by free fibula flap rapidly through 3D printing technique. METHODS: 3D models of reconstruction of unilateral maxillary defect by free fibula flap was established via CAD/CAM, metal customized plates and resin osteotomy guides were designed and manufactured via 3D printing technique, simulating operation was performed on models in vitro, and reconstructive accuracy after surgical simulation was analyzed using SPSS 18.0 software package. RESULTS: Digital models involving reconstructive bone and affiliated devices (plates and guides) were established and fabricated rapidly. There was no significant difference between simulating point on computer and surgical simulating point in vitro. CONCLUSIONS: The optimized design and customized plate can increase the accuracy of reconstruction of maxillary defects with free fibula in vitro, which is helpful for accurate surgical reconstruction.

[Comparative study of functional neck dissection and radical neck dissection for early oral squamous cell carcinoma].

PURPOSE: To evaluate the clinical effects of functional neck dissection(FND) and radical neck dissection(RND) on early oral squamous cell carcinoma (OSCC). METHODS: A total of 63 OSCC patients were divides into 2 groups. Patients in FND group (n=30) underwent functional neck dissection with preservation of sternocleidomastoid muscle, accessory nerve, internal jugular vein and great auricular nerve, while patients in RND group (n=33) underwent radical neck dissection. The follow-up data included movement of shoulder joint, great auricular nerve function, neck shape and local recurrent rate. SPSS 18.0 software package was used for data. RESULTS: There was no significant difference in age, gender, tumor location, T stage, N stage, histologic grades, pathological type, preoperative chemotherapy and postoperative chemotherapy between the two groups(P>0.05). Cervical lymph nodes was not palpable(N0) or the diameter was less than or equal to 3cm(N1) for all patients. Compared to RND, the activities of shoulder joint point, earlobe numbness and neck concave deformity were significantly improved with FND(P<0.05). Patients were followed up for 2 years, no significant difference was observed for neck recurrence between the two groups(P=1.000). CONCLUSIONS: FND can be safely performed in cN0 or cN1 OSCC patients, which avoids major complications with RND, and improves postoperative quality of life for OSCC patients with NO or N1 stage.

Quality of Life in Patients After Maxillectomy and Placement of Prosthetic Obturator.

PURPOSE: The aim of this study was to assess quality of life (QoL) and obturator functioning in patients having undergone a maxillectomy as a tumor ablative resection and rehabilitation with a prosthetic obturator. MATERIALS AND METHODS: The University of Washington Quality of Life scale version 4 (UW-QoLv4) and the Obturator Functioning Scale (OFS) were used to evaluate the self-reported QoL and obturator functioning. The effects of demographic and treatment variables on QoL were assessed using age, defect size, postoperative radiotherapy (RT), neck dissection, and dentition. RESULTS: The study included 16 men and 13 women with a mean age of 48.8 years. Of the 29 patients, 16 had a Brown Class 2a or smaller defect and 13 had a Brown Class 2b or larger defect. The mean OFS score (P = .004) and the physical (P = .001) and social-emotional function scores (P = .001) of the patients who received postoperative RT were significantly lower than those who did not receive postoperative RT. The subscales for swallowing (P = .008), saliva (P = .001), pain (P = .001), and shoulder function (P = .002) correlated strongly with postoperative RT on the UW-QoL. The subscales for pronunciation (P = .007) and saliva (P = .002) correlated significantly with RT on the OFS. The mean OFS scores were significantly lower for the patients with a Brown Class 2a or smaller defect than for Brown Class 2b or larger (P = .005). CONCLUSION: Postoperative RT was the strongest variable affecting QoL in patients with maxillectomy and prosthetic obturator reconstruction. The size of the defect slightly influenced the obturator function; however, it did not influence the overall QoL.

Circulating microRNA-21 (MIR-21) and phosphatase and tensin homolog (PTEN) are promising novel biomarkers for detection of oral squamous cell carcinoma.

The purpose of this study was to investigate the potential of the blood levels of MIR-21 and PTEN as novel biomarkers for oral squamous cell carcinoma (OSCC). We initially detected MIR-21 and PTEN using real-time RT-PCR from 90 blood samples and then compared their results with expression in cancer tissues from 10 OSCC patients. Finally, we examined the relationship between these markers and clinical parameters. Blood MIR-21 and PTEN had significant diagnostic value for OSCC and, to an extent, correlated with the expression level of tumour MIR-21 and PTEN. In addition, they were associated with differentiation and nodal status. Thus circulating MIR-21 and PTEN might represent new complementary tumour markers for OSCC.

Protein overexpression of CIRP and TLR4 in oral squamous cell carcinoma: an immunohistochemical and clinical correlation analysis.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy. Here, we evaluated the expression of cold-inducible RNA-binding protein (CIRP) and toll-like receptors 4 (TLR4) in OSCC tissues with immunohistochemistry. Using biostatistical methods designed to assess the impact of the expression of CIRP and TLR4 on the prognosis of patients with OSCC and relate that expression to the clinicopathological characteristics of these patients. For the first time, we demonstrated that the expression of CIRP and TLR4 was increased in OSCC and that high levels of CIRP or TLR4 expression were associated with a short survival rate. In addition, we were surprised to find that the levels of expression of CIRP and TLR4 were very similar. The goal of this study was to evaluate whether these two genes may provide clues as to the regulatory mechanisms of OSCC, serve as prognostic markers and establish a new direction for further studies of these biological mechanisms.

Decompression as a treatment for odontogenic cystic lesions of the jaw.

PURPOSE: To evaluate the effectiveness of decompression as the primary treatment of odontogenic cystic lesions of the jaw involving factors that affect relative shrinking speed and bone regeneration. PATIENTS AND METHODS: A total of 32 patients with odontogenic cystic lesions of the jaw underwent decompression with customized thermoplastic resin stents. Clinical examinations and pre- and postdecompression panoramic radiographs were analyzed. RESULTS: The mean relative speed of shrinkage of radicular cysts (RCs; 3.37 cm(2)/month) was faster than those of keratocystic odontogenic tumors (KCOTs; 2.87 cm(2)/month) and unicystic ameloblastomas (UABs; 2.71 cm(2)/month). The relative shrinking size increased linearly in a time-dependent manner for KCOTs (r = 0.849, P < .001), RCs (r = 0.681, P = .319), and UABs (r = 0.146, P = .730); a similar relation was detected between the primary radiolucent area of cystic lesions before decompression and relative shrinking speed after decompression in KCOTs (r = 0.481, P = .032), RCs (r = 0.260, P = .673), and UABs (r = 0.370, P = .366), but patient age did not affect the relative speed of shrinkage (P > .05). Furthermore, the increase in bone density was more significant in RCs than in KCOTs (P = .026) and UABs (P = .012) after decompression. CONCLUSION: Decompression was effective in reducing odontogenic cystic lesions of the jaw and increasing bone density. For aggressive lesions, secondary definitive surgery was necessary.

Clinical analysis of 194 cases of head and neck hamartoma.

OBJECTIVE: The aim of this study was to analyze the clinical management of hamartomas in the head and neck region (HNH). STUDY DESIGN: From January 1996 to December 2011, a retrospective analysis of 194 patients with HNH was performed. The preoperative examinations, surgical treatment, and prognosis were recorded and analyzed. RESULTS: Of the 194 patients, 107 were male and 87 female. Their ages ranged from 1 month to 82 years with a mean of 33 years. The most common locations were the oral mucosa (68.6%) and head and neck skin (27.3%). The course of disease ranged from 1 to 264 months with a mean of 66 months. Routine laboratory examinations were within normal limits. All patients underwent surgical removal of the lesions and prognosis was good. CONCLUSIONS: The clinical characteristics of HNH are not specific, and the clinical manifestation is always the same for benign tumors. The first choice of treatment is surgical excision, which results in a good prognosis.

[Study on relationship between expression of podoplanin and lymph node metastasis in oral squamous cell carcinoma].

PURPOSE: In oral squamous cell carcinoma(OSCC) and normal oral tissues, podoplanin was used to mark lymphatic tract and recorded the lymphatic vessel density (LVD) by corresponding tissue. The aim of this study was to evaluate LVD in correlation with lymphnode metastases in patients with OSCC. METHODS: The expressions of VEGF-C antibodies and anti-podoplanin were detected in 21 normal oral tissues and 88 paraffin sections of OSCC by immunohistochemistry(S-P); Determination of LVD (assessed by immunostaining for podoplanin) was performed as suggested by Weidner, the numerical value expressed by x±s Intratumoral lymphatic vessels (I-LVD) and peritumoral lymphatic vessels (P-LVD) were assessed, respectively. Data was analyzed with SPSS 13.0 software package and t test was used for comparative analysis of LVD between normal oral tissues and OSCC tissue and LVD (including P-LVD and ILVD) of the lymph node metastasis and without lymph node metastasis. RESULTS: There was significant difference between LVD of normal control tissues, peritumoral and intratumoral tissues.The intratumoral lymphatic vessels (ILVD) were small and collapsed, while the peritumoral ones were large and dilated. The PLVD's density with lymph node metastasis(14.270±4.610) was significantly higher than that without lymph node metastasis (9.450±2.411, P<0.05). CONCLUSION: The results indicated that peritumoral lymphangiogenesis may have an important impact on lymph node metastasis in OSCC.

[Clinical utilization of veiled incision and sternocleidomastoid flap in parotidectomy of parotid benign tumors].

PURPOSE: To describe a modified technique of parotidectomy using face-lift approach and sternocleidomastoid flap. METHODS: Forty-six patients were divided into two groups; group 1 (23 cases) using veiled incision and sternocleidomastoid flap, group 2 (23 cases) using traditional incision (Blair's approach) without sternocleidomastoid flap. Postoperative complications included temporary facial paralysis and salivary fistula. The follow-up period was 2 years, oncological recurrence was compared between the two groups. The incidence of Frey's syndrome and the feeling of the region around the auricular lobule were evaluated. The data was analyzed using SPSS10.0 software package with Student's t test and Chi-square test. RESULTS: During the follow up period, the patients in the group 1 showed better aesthetic results than those in the group 2 and without obvious scar and deformity. There was no significant difference between these two groups in temporary facial paralysis, salivary fistula, tumor recurrence, Frey's syndrome, the feeling of the region around the auricular lobule. CONCLUSION: The modified technique of parotidectomy using veiled incision and sternocleidomastoid flap greatly reduces the disadvantages of traditional parotidectomy and provides better aesthetic results.

[Killing effect of cytotoxicty T lymphocyte primed by two different methods preparation of dendritic cells pulsed with antigen on Tca8113 cells in vitro].

OBJECTIVE: To study the feasibility of dendritic cells (DCs) vaccine on the therapy of tongue carcinoma and find the better way of antigen load. METHODS: The antigen peptides of Tca8113 cells were obtained by acid eluted technique and repetitive freeze thaw method. Separating T cell and inducing dendritic cells were obtained from human peripheral blood monocyte. Divided into three groups: Weak acid elution method antigen group, anti-freeze-thaw method antigen group, and the control group (without tumor antigen). T cells and UCs were mixed to culture by different effector-target ratio. Using MTT assay measured the quantities of absorbance and calculated stimulation index. Dendrtic cells pulsed with antigen were mixed with T cells by different effector-target ratio. MIT assay was used to measure the quantities of absorbance and calculate killing rate. RESULTS: DCs vaccine was constructed successfully. DCs vaccine can induce T lymphocytes to kill Tca8113 cells and display the dose-effect relationship. There was significant difference among the three groups. The acid eluted and repetitive freeze thaw groups were better than the control group. The acid eluted group was better than repetitive freeze thaw group. CONCLUSION: DCs vaccine can induce T lymphocytes to kill Tca8113 cells. The antigen peptides obtained by acid eluted technique is better than repetitive freeze thaw method in immunotherapy of tongue cancer.

[Study of increased sensitivity on Tca8113 cell line to cisplatin by nm23-H1 in vitro].

OBJECTIVE: To study the mechanism of sensitivity variation to cisplatin caused by nm23-H1. METHODS: The samles was divided into two groups: Tca8113 group and Tca8113/nm23-H1 group. Using MTT and flow cytometer, the changes of cell mortality rate, apoptosis and mitochondrial membrane potential were detected. By VG PQ Excell, the changes of the intracellular platinum were detected. RESULTS: In vitro the cell mortality rate and apoptosis were increased in Tca8113/nm23-H1 group, comparing with Tea8113 group. Mitochondrial membrane potential was decreased in Tca8113/nm23-H1 group. The intracellular platinum was increased significantly in Tca8113/nm23-H1 group. This effect could be inhibited by oubain which was an inhibitor of Na+/K+-ATP. CONCLUSION: nm23-H1 can increase the sensitivity of cisplatin on Tca8113 cell line. The mitochondrial membrane potential was decreased by nm23-H1 so that intracellular platinum was increased and finally increased the apoptosis or necrosis.

[A clinical retrospective study on modified parotidectomy in benign tumors of parotid gland].

PURPOSE: A clinical perspective study was designed for patients undergoing a modified parotidectomy to reduce complications of parotidectomy. METHODS: 110 patients were divided randomly into two groups; Group 1 (55 cases) was operated via routine surgical modality. Group 2(55 cases) was treated with preserving the fascia parotideomasseterica and great auricular nerve and partial parotidectomy. Tumor size, blood loss, operating time, temporary facial paralysis, tumour recurrence were compared between the two groups. The follow-up period was 2 years. The incidence of Frey's syndrome was clinically evaluated by Minor test (starch-iodine test). The feeling of the region around the auricular lobule was also evaluated. The data were analyzed using SPSS10.0 software package for Student's t test and Chi-square test. RESULTS: There was no significant difference between the two groups in tumor size, temporary facial paralysis and tumor recurrence. Group 1 was significantly lower than that in Group 2 in the bleeding volume and operating time. The incidence rate of Frey's syndrome in Group 1 was significantly lower than that in Group 2 by objective observation and Minor test. There was significant difference between the feeling of pro- operation and pre-operation in the auricular lobule. CONCLUSIONS: The modified parotidectomy is a function-preserving surgery for benign parotid tumours, which improves the cosmetics, the feeling around ear, reduces the duration of surgery, and the incidence rate of Frey's syndrome. Supported by Research Fund of Science and Technology Bureau of Shanxi Province [Grant No.2005K14-G8(2)] and Science and Technology Project of Xi'an City [Grant No.SF08008-(4)].