高聚金葡素联合化学药物治疗口腔癌的疗效与免疫功能观察

目的 评价高聚金葡素 (HAS)联合化疗治疗口腔癌的疗效 ,以及免疫治疗在肿瘤化疗中的应用价值 ,着重从机体免疫状况以及细胞因子的调控方面 ,探讨其作用机理。方法 对 2 6例口腔癌进行颞浅动脉逆行插管术 ,分别进行化疗和 HAS联合化疗两种方式。观察疗效和药物毒副作用 ,并采用流式细胞技术、EL ISA法等测定其免疫状态。结果 治疗组总有效率为 80 % (8/ 10 ) ,无明显毒副作用 ,并减轻化疗所致的毒副作用。口腔癌患者细胞免疫受到不同程度地抑制 ,而体液免疫功能处于正常范围内 ,CIC值的升高与肿瘤免疫抑制相关。观察两组治疗前后免疫学指标 ,发现 HAS可刺激 T- CD+4 细胞增殖 ,并能分泌大量细胞因子如 IL - 2 ,进一步促进细胞免疫应答。化疗对免疫功能有明显的抑制作用 ,而经 HAS治疗后 CD4、CD4/ CD8比值、IL - 2升高较化疗组明显 (P<0 .0 5 )。所以使用 HAS可避免因化疗和手术等所致的术后早期免疫功能下降。但 HAS治疗组术后第二个月免疫功能受到抑制 ,与超抗原所致的免疫耐受有关。结论 高聚金葡素联合化疗疗效显著 ,可减少化疗所致的毒副作用。HAS主要通过刺激 T细胞增殖 ,调节细胞因子的分泌 ,达到增强免疫功能和抗癌目的 。

Expression of HMGB1 Protein in Human Cervical Squamous Epithelium Carcinoma

OBJECTIVE To investigate the expression of the high mobility group boxl（HMGB1） in human cervical squamous epithelial carcinoma （CSEC） and to explore the relationship of HMGB1 expression to the differentiation degree, size, invasion and metastasis of CSEC. METHODS Immunohistochemical staining of tissue microarrays and Western blot analysis were conducted to detect the expression of HMGB1 in the following tissue samples： 30 carcinoma in situ, 90 invasive CSEC without metastasis, 30 invasive CSEC with metastasis, 30 cases of normal cervical squamous epithelia. RESULTS The positive-expression rate of HMGB1 was 58.7% （88/150） in CSEC, showing a significant difference compared to normal cervical squamous epithelia. The expression of HMGB1 was correlated with tumor size, invasion and metastasis of CSEC （respectively, P〈0.01）, but had no relationship with the degree of differentiation （P〉0.05）. CONCLUSION The over-expression of HMGB1 in CSEC might be a useful parameter as an indication of tumor invasion, metastasis, prognosis and overall biological behavior of human CSEC, as well as a noval target site for gene therapy.

The Significance of CXCR4 Expression for the Prediction of Lymph Node Metastasis in Breast Cancer Patients

OBJECTIVE The chemokine receptor(CXCR4)CXC chemokine receptor 4)plays an important role in cancer metastasis.We therefore studied differential expression of the CXCR4,as well as that of the biomarker HER2,so as to evaluate whether these biomarkers can be used to predict axillary lymph node metastasis in breast cancer patients. METHODS Immunohistochemistry was used to evaluate the CXCR4 and HER2 expressions and to examine the paraffin sections of the breast cancers at various stages.Positive lymph node expression was found in 80 of the cases,and in 7 there was negative expression. RESULTS Compared to the cases with negative lymph nodes, there was a high expression of CXCR4(26.3% vs.14.3%,P=0.013), and an over-expression of HER2(28.8% vs.14.3%,P=0.011). Moreover,there was a direct correlation between the CXCR4 and HER2 expressions and the tumor staging(P=0.000)and lymph node metastasis(P=0.032).When the two biomarkers,i.e.CXCR4 and HER2,were concurrently labeled,a high expression of one of the biomarkers could be seen in the cases with positive lymph nodes(51.3% vs.28.6%,P<0.003). CONCLUSION The chemokine receptor,CXCR4,is a new-type biomarker in predicting axillary lymph-node metastasis in breast cancers.Compared with the other markers,such as HER2 etc., assessment of CXCR4 can improve the prediction of the presence and extent of lymph node involvement.

Expression and clinical significance of PTEN protein in osteosarcoma

Objective： To investigate the expression and significance of cancer inhibitory gene PTEN protein in osteosar-coma. To analyze the level of its expression in different histological classification of osteosarcoma. To determine the possibility of taking PTEN protein as a marker gene for diagnosing osteosarcoma. To observe the clinical value of PTEN expression levels as a reference index for osteosarcoma classification. Methods： 43 specimens collected from osteosarcoma excision were studied. 30 specimens collected during the same period from benign lesion of bone （osteochondroma） operation were taken as the control group. Immunohistochemistry staining （ElivisonTM two steps method） was used to detect the expression of PTEN protein in 43 cases of osteosarcoma. SPSS 10.0 was used in statistical analysis. Results： Immunohistochemistry staining showed that the positive reaction of PTEN protein was all oriented to cytoplasm, which were brown or yellowish- brown granules. By way of X^2 test, the significant difference of the positive expressions of PTEN protein between bone benign lesion and osteosarcoma （X^2 = 7.976, P 〈 0.01） was observed. Osteosarcoma with different degrees of histodifferentiation showed different level expression of PTEN protein. There was significant difference between well-differentiated osteosarcoma （grades Ⅰ-Ⅱ） and poorly-differentiated osteosarcoma （grade Ⅲ） statistically （P 〈 0.01）. The level of expression of PTEN was negatively correlated to the histological grade of osteosarcoma. There was great significance statistically （rs=-0.4922, P 〈 0.01）. Conclusion： PTEN protein may be used as candidate gene of cancer inhibitory gene： PTEN protein is a cancer suppressor gene protein which has expression in bone tumors. It might not only be used in the study of pulmonary carcinoma and neurogliocytoma, but also in the study of bone tumor; the expression of PTEN is related to benignancy or malignancy of bone tumor and their degree of differentiation. The expression of PTEN is positively correlated with degree of differentiation.

Overview of immunosuppression in liver transplantation

Continued advances in surgical techniques and immunosuppressive therapy have allowed liver transplantation to become an extremely successful treatment option for patients with end-stage liver disease.Beginning with the revolutionary discovery of cyclosporine in the 1970s,immunosuppressive regimens have evolved greatly and current statistics confirm one-year graft survival rates in excess of 80%. Immunosuppressive regimens include calcineurin inhibitors,anti-metabolites,mTOR inhibitors,steroids and antibody-based therapies.These agents target different sites in the T cell activation cascade,usually by inhibiting T cell activation or via T cell depletion.They are used as induction therapy in the immediate periand post-operative period,as long-term maintenance medications to preserve graft function and as salvage therapy for acute rejection in liver transplant recipients. This review will focus on existing immunosuppressive agents for liver transplantation and consider newer medications on the horizon.

Expression and role of AQP1 in cervical squamous carcinoma and its precancerous lesions

Objective： To investigate the expression of aquaporin 1 in cervical squamous carcinomas （CSC） and cervical precancerous lesions, and the relationship between the tumor clinicopathological parameters, prognosis and the expression of AQP1. Methods： Immunohistochemical method （EliVision） was used to detect the expression of AQP1 in samples from 106 patients [20 with normal cervical tissue, 30 with cervical intraepithelial neoplasia （stage Ⅰ and Ⅱ） and 56 with CSC]. Survival analysis was performed by Kaplan-Meier method. Results： AQP1 protein was expressed in vascular endothelia of all samples. It showed upregulation of AQP1 expression in CSC. There was a significant difference between CSC and normal cervical tissues （P〈0.05）. AQP1 was expressed in some tumor cells and unexpressed in normal squamous epithelial cells. And APQl-expressing tumor cells were positively related to lymph node metastasis. Patients with APQl-expressing tumor cells had the lower survival rate than the ones without. Conclusion： Abnormal expression of AQP1 plays an important role in the development of CSC. Positive expression of AQP1 in tumor cells maybe enhances tumor metastasis and could be used as a marker for tumor prognosis.

Clinicopathological Significance of E-cadherin and PCNA Expression in Hunman Non-small Cell Lung Cancer

OBJECTIVE This study was designed to assess E-cadherin (E-cad)and proliferating cell nuclear antigen(PCNA)expression as well as their clinicopathological significance in hunman non- small cell lung cancers(NSCLCs).Possible molecular mechanisms of differentiation and metastasis of NSCLCs are discussed. METHODS Immunohistochemical and immunofluorescence double staining were performed to examine the expression of E-cad and PCNA in 68 primary NSCLCs cases. RESULTS The E-cad expression in squamous cell carcinomas and adenocarcinomas showed no significant difference.E-cad expression had a positive correlation with the histological- differentiated grade.A significant difference of E-cad expression was found between metastatic and non-metastatic groups.PCNA expression in squamous cell carcinomas and adenocarcinomas showed no significant difference.The PCNA expression had a reverse correlation with the histological-differentiated grade.A significant difference of PCNA expression was found between metastatic and non-metastatic groups.The E-cad and PCNA expression presented a reverse correlation. CONCLUSION E-cad expression is not associated with the histological type of NSCLC,but is associated with differentiation and metastasis of the cancer.Down-regulation of E-cad expression affects the proliferation of cancer cells.Conjoint analysis of E-cad and PCNA expression is a good way to evaluate tumor biological behavior.

Effects of gemcitabine and cisplatin chemotherapy in advanced non-small cell lung cancer patients with RRM1 low protein expression

Objective： The aim of this study was to observe the efficacy of gemcitabine combined with cisplatin （GP） in advanced non-smaU cell lung cancer （NSCLC） patients with low expression of ribonucleotide reductase 1 （RRM1） protein using immunohistochemistry. Methods： RRM1 protein expression in tumor tissue was detected by streptavidin-peroxidase （SP） method of immunohistochemistry. GP regimen （gemcitabine 1000-1250 mg d1, d8, cisplatin 75 mg/m2） was given to advanced NSCLC patients with low expression of RRM1 protein. Results： In the total of 40 patients, these patients with RRM1 low expression performing GP chemotherapy had a good response rate, the objective response rate （ORR） was 47.5% （95% CI, 32.02%- 62.98%）, and the disease control rate （DCR） was 72.5% （95 % CI, 65.44%-79.56%）. ORR is 45.45% （5/11） in the squamous cell carcinoma patients while 48.15% （13/27） in the adenocarcinoma patients. Conclusion： Supedor ORR and DCR were found in advanced NSCLC patients with low expression of RRM1 protein expression performing GP regimen.

Analysis of the Relationship between Expressions of TF and MMP-9 and Prognosis of Breast Cancer Patients

OBJECTIVE To investigate expression of the tissue factor (TF)and matrix metalloproteinase-9(MMP-9)in breast cancers, and to assess their expression in relation to possible prognostic significance. METHODS The expression of TF and MMP-9 in 71 breast cancer specimens were determined by EnVision immunohistochemistry, and the positive expressions related to the patient clinical outcome. RESULTS Positive rates of TF and MMP-9 staining were respectively 43.7%and 42.3%.K-M monofactorial analysis showed that the 5-year survival rate of the patients with a positive expression of TF and MMP-9 was lower than those with negative expression(P<0.05).However,the COX multifactorial analysis indicated that TNM staging and lymph node metastasis were the prognostic factors for breast cancer patients,and that TF and MMP-9 could not be used as the independent prognostic factors(P >0.05). CONCLUSION The positive rates of TF and MMP-9 were considerably high in breast cancers,which could provide useful information for patient prognosis.

食管癌新辅助免疫治疗的现状及未来

免疫检查点抑制剂(ICIs)已经成为晚期食管癌一线、二线治疗的重要策略之一。目前ICIs在新辅助治疗阶段的使用非常有限。在肿瘤免疫治疗的大背景下,新辅助免疫治疗可能对早期食管癌或可手术切除的局部晚期食管癌病人带来更佳生存获益。笔者查阅国内外相关文献,探讨食管癌新辅助免疫治疗的现状及未来。

Therapeutic effects of human amniotic epithelial cell transplantation on double-transgenic mice co-expressing APPswe and PS1ΔE9-deleted genes

Human amniotic epithelial cells (HAECs), which exhibit characteristics of embryonic and pluripotent stem cells, could be utilized for cell therapy without legal or ethical problems. Double-transgenic (TG) mice (n=20) and wild-type (WT) mice (n=20) were randomly assigned to two groups, respectively. The transplantation group was treated with HAECs and the control group with PBS. A six-radial arm water maze was used to assess spatial memory. Immunofluorescence was utilized to track HAEC survival. Immunohistochemistry was used to determine octamer-binding protein 4 (oct-4) and nanog expression in the HAECs. High-performance liquid chromatography (HPLC) was used to measure acetylcholine levels in the hippocampus. The density of cholinergic neurons in the basal forebrain and nerve fibers in the hippocampus was measured following acetylcholinesterase staining. Results showed that transplanted HAECs survived for at least eight weeks and migrated to the third ventricle without immune rejection. Graft HAECs also expressed the specific stem cell markers oct-4 and nanog. Compared with the control group, HAEC transplantation significantly ameliorated spatial memory deficits in TG mice, as well as increased acetylcholine levels and the number of hippocampal cholinergic neurites. Intracerebroventricular HAEC transplantation improved spatial memory in double-TG mice, and results suggested that increased acetylcholine levels in the hippocampus, released by surviving cholinergic neurites, were responsible for this improvement.