Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it's imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI^- towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
Schwann Cells/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Cancer-Associated Fibroblasts/metabolism* ; Animals ; Carcinoma, Squamous Cell/metabolism* ; Neoplasm Invasiveness/pathology* ; Male ; Female ; Mice ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Cell Line, Tumor ; Leukemia Inhibitory Factor/metabolism* ; Middle Aged

Purpose To analyse the expression of aldo-keto reductase AKR1C3 in the tumour tissues of oral squa-mous carcinoma(OSCC)and the correlation of clinical prognosis of patients.Methods Immunohistochemical(IHC)staining was performed to analyze the expression characteristics of AKR1C3 in 86 cases of OSCC tumor tissues and paired paratumor normal tissue.The correlation between AKR1C3 expression and clinical prognosis was evaluated.Ka-plan-Meier survival analysis was conducted to assess the survival outcomes of OSCC patients.Univariate and multivari-ate Cox regression analyses were employed to identify prognostic factors.The findings were further validated by compar-ison with the Cancer Genome Atlas(TCGA)database.Results The expression of AKR1C3 was significantly higher in OSCC tumor tissues than in paratumor normal tissue,with higher expression observed at the invasive front relative to the tumor centers.Immunohistochemical analysis revealed high expression in both tumor cells and tumor-associated fibro-blasts,while no expression was detected in tumor-infiltrating immunocytes.The x2 test was used to compare the rela-tionship between different expression levels of AKR1C3 and clinicopathological features in OSCC,the results showed that high expression of AKR1C3 was strongly associated with higher tumour stage(P=0.001),lymph node metastasis(P=0.023),differentiation(P=0.018),worst pattern of invasion(P=0.024)and depth of invasion(P=0.012).Kaplan-Meier survival curve analysis showed high expression of AKR1C3 was associated with overall survival(P=0.004),disease-free survival(P=0.019),and metastasis-free survival(P=0.05)in OSCC patients.Cox re-gression model was performed for prognostic analysis.Univariate analysis showed that high expression of AKR1C3 in tumour cells was a high-risk factor for patients' tumour stage(P＜0.001),lymph node metastasis(P＜0.001),dif-ferentiation(P＜0.001),worst pattern of invasion(P＜0.001),depth of invasion(P＜0.001).Multivariate analy-sis further showed that high expression of AKR1C3 in tumour cells was an independent prognostic factor in OSCC pa-tients(P=0.025).Conclusion The AKR1C3 expression is closely related to the prognosis of OSCC patients,and patients with high AKR1C3 expression have a poor prognosis,suggesting that AKR1C3 plays an important role in the occurrence and development of OSCC.

Purpose To analyse the expression of aldo-keto reductase AKR1C3 in the tumour tissues of oral squa-mous carcinoma(OSCC)and the correlation of clinical prognosis of patients.Methods Immunohistochemical(IHC)staining was performed to analyze the expression characteristics of AKR1C3 in 86 cases of OSCC tumor tissues and paired paratumor normal tissue.The correlation between AKR1C3 expression and clinical prognosis was evaluated.Ka-plan-Meier survival analysis was conducted to assess the survival outcomes of OSCC patients.Univariate and multivari-ate Cox regression analyses were employed to identify prognostic factors.The findings were further validated by compar-ison with the Cancer Genome Atlas(TCGA)database.Results The expression of AKR1C3 was significantly higher in OSCC tumor tissues than in paratumor normal tissue,with higher expression observed at the invasive front relative to the tumor centers.Immunohistochemical analysis revealed high expression in both tumor cells and tumor-associated fibro-blasts,while no expression was detected in tumor-infiltrating immunocytes.The x2 test was used to compare the rela-tionship between different expression levels of AKR1C3 and clinicopathological features in OSCC,the results showed that high expression of AKR1C3 was strongly associated with higher tumour stage(P=0.001),lymph node metastasis(P=0.023),differentiation(P=0.018),worst pattern of invasion(P=0.024)and depth of invasion(P=0.012).Kaplan-Meier survival curve analysis showed high expression of AKR1C3 was associated with overall survival(P=0.004),disease-free survival(P=0.019),and metastasis-free survival(P=0.05)in OSCC patients.Cox re-gression model was performed for prognostic analysis.Univariate analysis showed that high expression of AKR1C3 in tumour cells was a high-risk factor for patients' tumour stage(P＜0.001),lymph node metastasis(P＜0.001),dif-ferentiation(P＜0.001),worst pattern of invasion(P＜0.001),depth of invasion(P＜0.001).Multivariate analy-sis further showed that high expression of AKR1C3 in tumour cells was an independent prognostic factor in OSCC pa-tients(P=0.025).Conclusion The AKR1C3 expression is closely related to the prognosis of OSCC patients,and patients with high AKR1C3 expression have a poor prognosis,suggesting that AKR1C3 plays an important role in the occurrence and development of OSCC.

Objective To investigate the relationship between the frequency of peripheral blood natural killer cells (NK) and HLA-Cw alleles in liver cirrhotic patients with chronic HBV infection and a-cute hepatitis B patients. Methods Thirty liver cirrhotic patients and 30 patients with acute hepatitis B were included in our study, and 41 healthy individuals were enrolled as controls. The numbers of circulating NK cells and activated NK ceils were analyzed by flow cytometry. HLA-Cw genotyping was conducted with polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO). Results The numbers of circu-lating NK cells and activated NK cells in liver cirrhotic patients were 13.22% ± 4.61% and 45.68% ± 14.64%, which was lower than that in healthy subjects (P < 0.05). The numbers of circulating NK cells and activated NK cells in acute hepatitis B patients were 22.62% ± 3.70% and 65.28%± 14.45%, which was higher than that in healthy subjects(P < 0. 05). There were statistically significant differences between the two groups(P < 0.01). The allele frequency of HLA-Cw * 15 in the patients with cirrhosis was signifi-cantly higher than that in the healthy (P < 0.05), and there was a significant negative correlation between the frequency of HLA-Cw * 15 and the numbers of activated NK cells in liver cirrhosis(r =4). 862, P < 0.05). No statistically significance was found between the group of acute hepatitis B and healthy subjects a- bout HLA-Cw(P > 0. 05). Conclusion The function of NK cells in liver cirrhotic patients is low, HLA-Cw * 15 gene may be one of the causes of effecting the antiviral function of NK ceils to induce the persistence of hepatitis B virus(HBV) infection.

Monoclonal antibodies against FMDV vp2 protein were prepared and a competitive ELISA based on the monoclonal antibodies and vp2 protein was established. Balb/c mice were immunized with Escherichia coli expressed fusion protein. The splenocytes from immunized mice were fused with myeloma cells SP2/0. The hybridism cells were screened by indirect ELISA and limited dilution method. Two hybndoma cell Iines secreting mAbs against Asia I type foot-and-mouth disease were obtained. The titer and relative affinity of mAbs were determined by ELISA. Specificity of mAbs was analyzed by Western blotting. The ELISA titers of the ascites induced by the two hybridism cells were above 100 x 2(9).A competitive ELISA for the use of FMDV antibody detection was established using E. coli expressed fusion protein as coating antigen and HRP-labled mAb as detecting antibody. Clinical tests showed the method had 89.0 percent agreement with UBI Kit to detection of FMDV antibodies and 86.5 percent agreement with LPB- ELISA kit (Ceditest kit) for detection of antibodies against Foot-and-Mouth Disease Virus respectively.
Animals ; Antibodies, Monoclonal ; biosynthesis ; immunology ; Antibodies, Viral ; blood ; Capsid Proteins ; immunology ; Enzyme-Linked Immunosorbent Assay ; methods ; Female ; Foot-and-Mouth Disease ; immunology ; virology ; Foot-and-Mouth Disease Virus ; immunology ; Mice ; Mice, Inbred BALB C ; Swine