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 molecules.

ABSTRACTClC‐3 chloride channel has been proved to have a relationship with the expression of osteogenic markers during osteogenesis, persistent static compression can upregulate the expression of ClC‐3 and regulate osteodifferentiation in osteoblasts. However, there was no study about the relationship between the expression of ClC‐3 and osteodifferentiation after dynamic compression. In this study, we applied dynamic compression on MC3T3‐E1 cells to detect the expression of ClC‐3, runt‐related transcription factor 2 (Runx2), bone morphogenic protein‐2 (BMP‐2), osteopontin (OPN), nuclear‐associated antigen Ki67 (Ki67), and proliferating cell nuclear antigen (PCNA) in biopress system, then we investigated the expression of these genes after dynamic compression with Chlorotoxin (specific ClC‐3 chloride channel inhibitor) added. Under transmission electron microscopy, there were more cell surface protrusions, rough surfaced endoplasmic reticulum, mitochondria, Golgi apparatus, abundant glycogen, and lysosomes scattered in the cytoplasm in MC3T3‐E1 cells after dynamic compression. The nucleolus was more obvious. We found that ClC‐3 was significantly up‐regulated after dynamic compression. The compressive force also up‐regulated Runx2, BMP‐2, and OPN after dynamic compression for 2, 4 and 8 h. The proliferation gene Ki67 and PCNA did not show significantly change after dynamic compression for 8 h. Chlorotoxin did not change the expression of ClC‐3 but reduced the expression of Runx2, BMP‐2, and OPN after dynamic compression compared with the group without Cltx added. The data from the current study suggested that ClC‐3 may promotes osteogenic differentiation in MC3T3‐E1 cell after dynamic compression. J. Cell. Biochem. 118: 1606–1613, 2017. © 2016 Wiley Periodicals, Inc.

Nucleoporin 88 (Nup 88) is a component of the nuclear pore complexes (NPCs) that mediates nucleocytoplasmic trafficking of macromolecules, Nup 88 has been reported to be up-regulated in a wide variety of malignancies. Studies show that overexpression of this antigen is associated with the development, agressiveness, differentiation and prognosis in some tumours. Since no study has been carried out in the relationship between the Nup 88 expression and clinicopathological features in the patients with oral squamous cell carcinoma (OSCC), this study aimed to determine Nup 88 expression in OSCC and its clinicopathological significance. Nup 88 expression was examined by immunohistochemistry in 20 normal oral mucosa specimens and 83 OSCC tissues. The frequency of positive Nup 88 expression was gradually increased from normal oral mucosa (10%) to primary OSCC (40%, P=0.012). The Nup 88 positive rate in OSCC patient with nodal metastasis was significantly higher than those without nodal metastasis (64% vs. 21%, P=0.000085). The frequency of positive Nup 88 expression was significantly different between worse and better differentiation (80 vs. 27%, P=0.000024). Nup 88 expression was not related to the patients' gender, age, location and tumour size (P>0.05). In conclusion, Nup 88 may play an important role in tumorigenesis in oral squamous cell carcinoma. Upregulation of Nup 88 is associated with nodal metastasis and poor differentiation in oral squamous cell carcinoma.

Basic transcription factor 3 (BTF3) is a general RNA polymerase II transcription factor and is also involved in apoptosis regulation. Increasing evidence shows that BTF3 is aberrantly expressed in several kinds of malignancies, but there is no study to analyze BTF3 expression in colorectal cancer (CRC) patients. Applying immunohistochemistry, we detected BTF3 in CRCs (n = 156), the corresponding distant (n = 42), adjacent normal mucosa (n = 96), lymph node metastases (n = 35), and analyzed its relationships with clinicopathological and biological variables. Our results showed that BTF3 staining significantly increased from distant or adjacent normal mucosa to primary CRCs (p < 0.0001) or metastases (p = 0.002 and p < 0.0001). BTF3 was higher in distal cancers than in proximal cancers (57 % vs. 39 %, p = 0.041). It also showed stronger staining in primary CRCs stage I and II than that in stage III and IV (64 % vs. 35 %, p = 0.0004), or metastases (64 % vs. 29 %, p = 0.004). Cancers with better differentiation had a higher expression than those with worse differentiation (56 % vs. 37 %, p = 0.031). There were positive correlations of BTF3 expression with nuclear factor kappa B (NF-κB), RAD50, MRE11, NBS1, and AEG-1 (p < 0.05). In conclusion, BTF3 overexpression may be an early event in CRC development and could be useful biomarker for the early stage of CRCs. BTF3 has positive correlations with NF-κB, RAD50, MRE11, NBS1 and AEG-1, and might influence complex signal pathways in CRC.

Background: Expression of WRAP53 protein has oncogenic properties and it is up regulated in several types of tumors.Methods: We examined expression of WRAP53 protein in rectal cancers and analyzed its relationship to the response to preoperative radiotherapy and patient survival. The WRAP53 protein was examined by immunohistochemistry in normal mucosa, primary tumors and lymph node metastases from 143 rectal cancer patients participated in a Swedish clinical trial of preoperative radiotherapy.Results: Frequency of WRAP53 protein expression was increased in primary rectal cancer compared to the normal mucosa (p < 0.05). In non-radiotherapy group positive WRAP53 in primary tumors (p = 0.03, RR, 3.73, 95% CI, 1.13-11.89) or metastases (p = 0.01, RR, 4.11, 95% CI, 1.25-13.14), was associated with poor prognosis independently of stages and differentiations. In radiotherapy group, positive WRAP53 in the metastasis correlated with better survival (p = 0.04). An interaction analysis showed that the correlations of WRAP53 with the prognostic significance with and without radiotherapy in the metastasis differed (p = 0.01). In the radiotherapy group, expression of WRAP53 in metastases gave a better outcome (p = 0.02, RR, 0.32, 95% CI, 0.13-0.84), and an interaction analysis showed significance between the two groups (p = 0.01).Conclusion: WRAP53 may be a new biomarker used to predict prognosis and to select suitable patients for preoperative radiotherapy.

MAC30 protein expression was examined by immunohistochemical ABC method in 20 cases of normal oral mucous tissue and 43 cases of oral squamous cell carcinoma(OSCC).MAC30 expression level in OSCC was higher than in normal mucosa(P<0.05).MAC30 expression level in patients with lymph node metastasis and/or with low differentiation was higher than in those without lymph node metastasis and/or with high differentiation(P<0.05).MAC30 may play an important role in the tumorgenesis,development and metastasis of OSCC.

We investigated whether SPARCL1 played an essential role in tumor initiation, formation and progression of colorectal carcinomas. In this study, we examined expression of SPARCL1 protein in the normal colorectal mucosa, adjacent normal mucosa and primary and lymph node metastases from colorectal cancer patients. In matched patients, we found that SPARCL1 was negative in the distant normal colorectal mucosa, weakly expressed in the adjacent normal mucosa, strongly expressed in primary colorectal adenocarcinomas and slightly expressed in their lymph node metastases. A similar pattern was observed in the SPARCL1 expression from our series of non-matched colorectal cancer patients. The strongest expression and highest frequency of the SPARCL1 protein were found in the primary cancers. Interestingly, in the primary tumors, the frequency of SPARCL1 expression was significantly increased from the Dukes' A to Dukes' B tumors and then decreased gradually from the Dukes' B to C and D tumors. There was no difference in the intensity of SPARCL1 expression between the central areas and invasion margins of the primary tumors. Moreover, the SPARCL1 protein was more strongly expressed in the highly differentiated tumors than the lower differentiated ones. The patients with positive expression of SPARCL1 in their tumors had worse prognosis than the patients with SPARCL1-negative ones, even after the analyses by Multivariate and Interaction method. Expression of SPARCL1 protein might be a valuable biomarker for early diagnosis in colorectal cancers and further predicting patients' prognosis.

Background: Expression of the meningioma-associated protein (MAC30) was increased in several types of tumors, including esophageal, gastric and colon tumors, compared to normal tissue. MAC30 expression levels gradually increased from normal colorectal mucosa to primary colorectal cancer and colorectal cancer spreading to the lymph nodes. MAC30 expression was related to survival in patients with colorectal cancer. However, there is no study on MAC30 in oral squamous cell carcinoma (OSCC). Methods: Therefore, MAC30 expression in OSCC was investigated and possible associations of MAC30 expression with clinicopathological variables in OSCC have been analyzed. MAC30 expression was immunohistochemically examined in 20 normal oral mucosa and 43 OSCC specimens. Results: Expression levels of MAC30 in the cytoplasm markedly increased from normal oral epithelial cells to primary OSCC. Strong cytoplasmic staining was significantly higher in primary OSCC compared to normal oral mucosa samples (51 vs. 20%, p = 0.019). Furthermore, MAC30 expression levels in primary tumors of patients with lymph node metastasis exceeded levels in those without metastasis (65 vs. 35%, p = 0.048), and MAC30 expression in poorly differentiated tumors was higher than in well-differentiated ones (90 vs. 39%, p = 0.005). Conclusion: Overexpression of MAC30 in the cytoplasm of OSCC may predict nodal metastasis and poor differentiation.

Objective To study the COX-2 and PINCH Protein expression in oral squamous cell carcinoma and the relationship between them.Methods ABC immunohistochemical method was used to investigate the expression of COX-2 and PINCH protein in paraffin block of 20 normal oral mucous tissue and 57 oral squamous cell carcinoma(SCC) cases.Analyze the relationship between the expression of COX-2 and the patients clinical variables and its relationship with PINCH protein.Results Immunostaining of COX-2 was low in normal oral mucous tissue and increased in oral SCC.The statistically difference was significant(P0.05).The positive rate of COX-2 expression was 73%(12/26) and 29%(9/31) of the lymph node metastasis group and the non-metastasis group respectively(P0.05).The COX-2 expression was not obviously correlated with patients gender,differentiation,age,location and tumor size(P0.05).COX-2 has a positive relationship with PINCH protein.Conclusion COX-2 may play an important role in the tumorgenesis and development of oral SCC,COX-2 may be related with the lymph node metastasis of OSCC and related with PINCH protein which can promote the lymphangenesis.

Objective:To study the Nup88 protein expressions in oral squamous cell carcinoma and to evaluate its clinicopathological significance.Methods:ABC immunohistochemical method was used to investigate the expressions of Nup88 in 20 normal oral mucosa and 57 oral squamous cell carcinoma(SCC).Analyzed the relationship between the expressions of Nup88 and the clinical variables.Results:Expressions of Nup88 was low in normal oral mucous tissue and increased in oral SCC,especially at the invasive border.The statistical difference was significant(P0.05).The positive rate of Nup88 expression was 73%(19/26)and 29%(9/31) of the lymph node metastasis group and the non-metastasis group(P0.05)respectively.The positive rate of Nup88 expression was 75%(12/16) and 21%(9/41) of the low differentiation group and the high differentiation group(P0.05).The Nup88 expression was not obviously correlated with patients gender,age,location and tumor size(P0.05).Conclusion:Nup88 may play an important role in the tumorgenesis and development of oral SCC.Nup88 may be a new biological marker in promoting metastasis of OSCC.Moreover,the positive Nup88 may suggest a high metastasis rate.

p33ING1b, as a candidate tumour suppressor gene, has been found to be expressed a proportion of oral squamous cell carcinomas (OSCCs), however, its clinicopathological significance is not studied yet. Our aim was to investigate association of p33ING1b expression with clinicopathological variables and particularly interesting new cysteine–histidine rich protein (PINCH) in OSCCs.

目前,2型糖尿病的发病率在全球呈逐年升高的趋势,而在糖尿病和牙周病的关系研究中发现,在糖尿病患者中牙周病的发病率高,病损严重且进展迅速[1,2],且糖尿病的糖代谢状况影响牙周病的愈合.而牙周病这种由菌斑微生物引起的感染性疾病,目前是人类失牙的主要原因之一.

Objective:To study the expression and clinical significance of P33~ ING1b protein in oral squamous cell carcinoma(OSCC). Methods:ABC immunohistochemical method was used to investigate the expression of P33~ ING1b protein in paraffin blocks of 20 cases of normal oral mucosa and 57 of OSCC. The relationship between P33~ ING1b expression and clinical data of the patients was analyzed. Results:In normal oral mucosa P33~ ING1b protein was observed mostly in cell nuclear, but in OSCC in cell nuclear and cytoplasm. P33~ ING1b was expressed in 90.00 % of the cases of normal mucosa and 24.56% of OSCC(P<0.05).The positive rate of P33~ ING1b protein expression was 46.15%(12/26) in lymph node metastasis group and 6.45%(2/31) in non-metastasis group(P<0.05). The P33~ ING1b protein expression was not correlated with gender, age, as well as tumor location(P> 0.05 ). Conclusions:The P33~ ING1b may play an important role in the tumorgenesis and development of OSCC,one of the mechanism most probably is the translocation of the protein from nuclear to cytoplasm.

Particularly interesting new cysteine-histidine rich protein (PINCH), an adapter protein involved in integrin and growth factor signalling, is up-regulated in the stroma of colorectal, breast, prostate, lung and skin cancer. Strong stromal immunostaining for PINCH is an independent prognostic indicator for reduced survival in colorectal cancer, suggesting that PINCH is involved in the signalling that promotes tumour progression. Since no study on PINCH has been carried out in oral squamous cell carcinoma (OSCC), this study aimed to determine PINCH expression in OSCC and its clinicopathological significance. PINCH protein expression was examined by immunohistochemistry in 20 normal oral mucosa and in 57 OSCC specimens. The frequency of strong PINCH immunostaining was higher in tumour-associated stroma of OSCC (37%) as compared to normal oral mucosa (10%) (p=0.02). Strong PINCH stromal immunostaining predicted nodal metastasis: 19/26 (73%) OSCC cases with nodal metastasis had strong PINCH immunostaining compared to 9/31 (29%) cases without nodal metastasis (p=0.02). The PINCH expression in OSCC was more intense in stroma at the invasive edge than in intratumoural stroma. In conclusion, the up-regulation of PINCH protein in stroma may be involved in promoting invasion and metastasis in OSCC.