Prospect of Tumor Treatment in the Post-PD-1/PD-L1 Inhibitor Era / 肿瘤防治研究

Immune checkpoint inhibitors restart and maintain cancer-immunity circulation to normalize the anti-tumor immunity. Currently, anti-PD-1/PD-L1 antibodies, as new milestone in immunotherapy, have significantly improved the prognosis of patients with various malignant tumors. However, anti-PD-1/PD-L1 antibody alone exhibited a low response rate, and the combination of anti-PD-1/PD-L1 antibody with traditional therapies such as surgery, chemotherapy, radiotherapy and targeted therapy have shown great potential. As new immune checkpoint inhibitors or in combination therapy are on the way, tumor immunotherapy is entering the era of post-anti-PD-1/PD-L1 antibody. The methodology of combination therapy and biomarker screening remain the focus. This paper reviews the current status of immune checkpoint inhibitor therapy and makes a perspective for the future of post-anti-PD-1/PD-L1 antibody era.

Research progress of Helicobacter pylori vaccine / 细胞与分子免疫学杂志

Helicobacter pylori (Hp) is one of most common pathogens causing gastrointestinal disorder including gastric ulcer, duodenal ulcer and gastric cancer, etc. It has been verified as class I carcinogen by WHO. Nowadays, combination antibiotics and proton pump inhibitor are mainly used to erase Hp in clinical application. However, with the increased resistance of Hp, the vaccine against Hp might become the best strategy to eradicate Hp. Elements including urease, virulence factor, outer membrane protein, flagella, play an important role in Hp infection, colonization and reproduction. They have become potential candidate antigens in the development of Hp vaccine, as reported in previous studies. Presently, these antigens-centric vaccines have been tested in animal models. Therefore, this article reviews the studies on Hp vaccine with urease, virulence genes, outer membrane protein and flagella as their candidate antigens, in an attempt to provide insights for research in this regard.

IFN-γ Inhibits Proliferation and Migration of Esophageal Squamous Cell Carcinoma by Downregulating CXCL8 Expression / 肿瘤防治研究

Objective To investigate the effect of IFN-γ on the proliferation and migration of esophageal squamous cell carcinoma cell line Eca9706 and related mechanism. Methods Cells were cultured in vitro and treated with interferon-γ. Cell morphology changes were observed under microscope, cell proliferation ability was detected by CCK-8 experiment, and cell migration ability was detected by cell scratch experiment and Transwell experiment. Real-time PCR method was used to detect the expression efficiency of chemokine CXCL8 (interleukin 8), and the ELISA experiment was used to detect the change of CXCL8 secretion. Results Compared with the blank control group, Eca9706 cells treated with different concentrations of interferon-γ did not change significantly in cell morphology. CCK8 experiment confirmed that the proliferation ability of Eca9706 cells after IFN-γ treatment was significantly reduced (P < 0.01). Cell scratch experiment found that IFN-γ significantly decreased the migration ability of Eca9706 cells (P < 0.01). Transwell experiment showed that after IFN-γ treatment, the migration ability of Eca9706 cells was significantly inhibited (P < 0.01). CXCL8 gene expression level in Eca9706 cells treated with interferon-γ was significantly down-regulated (P < 0.01), and the amount of CXCL8 secretion significantly reduced (P < 0.05). Conclusion Interferon-γ can inhibit the proliferation and migration of esophageal cancer cell line Eca9706, which may be related to its inhibition of the expression and secretion of CXCL8.

Efficacy and Safety of Immune Checkpoint Inhibitors Therapy on Advanced Gastric Cancer or Gastroesophageal Junction Cancer: A Meta-analysis / 肿瘤防治研究

Objective To systematically evaluate the efficacy and safety of immune checkpoint inhibitors in the treatment of advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC). Methods CNKI, Wanfang, PubMed, EMBASE, ClinicalTrials, Cochrane Library and other databases were searched to collect the clinical trials of immune checkpoint inhibitors in the treatment of advanced GC/GEJC. The retrieval time was from the inception to Nov. 2019. Outcome measures mainly included ORR, DCR, PFS, OS and toxicities. The adoption rate difference and hazard ratio were effect measures. Meta-analysis was performed using RevMan 5.3 software. Results We included seven literatures with a total of 1949 patients. Meta-analysis showed that for the patients with advanced GC/GEJC, the second-line or later immune checkpoint inhibitor therapy improved the overall survival rate at 12 and 18 months; the OS of the patients was prolonged, compared with chemotherapy/placebo therapy (all P < 0.05). The incidence of adverse reactions of any grade or ≥grade 3 caused by immune checkpoint inhibitor therapy was lower than that caused by chemotherapy/placebo. Conclusion Immune checkpoint inhibitor treatment could improve survival endpoints in some patients with advanced GC/GEJC, and the incidence of common adverse reactions is low.

Clinical analysis of 2 261 cases of esophageal cancer / 重庆医学

Objective To analyze the clinical features and onset factors of esophageal cancer.Methods The SPSS 13.0 software was adopted to establish the computer records management system of esophageal cancer.The clinical data in 2 261 clinically cured discharged cases of esophageal cancer from January 2011 to December 2013 were statistically analyzed.Results Forty-nine cases (2.17％) were in the 30-＜40 years old group,324 cases (14.33％) were in the 40-＜50 years old group,963 cases (42.59％) were in the 50-＜60 age group,790 cases (34.94％) were in the 60-＜70 age group and 135 cases (5.97％) were in the 70 years old or more group.Among 2 240 cases,2 031 cases (90.36 ％) showed the different differentiation degrees of squamous epithelial carcinoma by histological analysis,the invaded range displayed fibrous membrane(T3) in 759 cases(33.57％) and peripheral tissue(T4) in 682 cases(30.16％);having smoking and drinking history was in 1 281 cases(56.67％) and 1 025 cases (45.33 ％) respectively;596 cases (26.36 ％) had genetic family history,75.08 ％ was father positive or mother positive.Conclusion Esophageal cancer is mainly squamous cell carcinoma,the onset age is mainly concentrated at the age 50-＜70 years old,which is correlated with smoking and drinking years,moreover has obvious genetic susceptibility.

Analysis of colorectal cancer incidence and mortality rates during the last 40 years in Hebei Province / 中国癌症杂志

Background and purpose: Colorectal cancer is one of the most common gastrointestinal cancers. There were about 1.36 million new cases of colorectal cancer, which was the third highest incidence of malignant tu-mors of the world in 2012. It was the fourth leading cause of cancer death and became a serious threat to human health. The aim of the study was to estimate the colorectal cancer burden in Hebei Province with the data of cancer registries areas and analyze the trend of colorectal cancer mortality rates with three of the Hebei Province death retrospective surveys. Methods: Nine cancer registries in Hebei Province submitted cancer registry data from 2010 to 2012 to the Hebei Provincial Cancer Registry Center. The pooled data were stratified by gender and age (0, 1-4, 5-9, 10-14…80+). Proportions and incidence/mortality rates for colorectal cancer were calculated. Incidence and mortality rates were age-standardized to Chinese population census in 2000 and world Segi's population standard. Colorectal cancer mortal-ity data during the periods 1973-1975, 1990-1992 and 2004-2005 were extracted from the death retrospective surveys and analyzed. Mortality and incidence rate data from Cixian County from 1988 to 2012 and Shexian County from 2000 to 2012 were obtained in each county and analyzed using Joinpoint regression model. Results: The estimated number of newly diagnosed colorectal cancer cases and deaths from 2010 to 2012 in cancer registry areas of Hebei Provinc were 2303 and 1229, respectively. The crude incidence rate of colorectal cancer was 16.48/100000 (male 18.12/100000 and female 14.77/100000). The age-standardized incidence rate by Chinese population census (ASRC) in 2000 was 13.74/100000. The colorectal cancer mortality rate was 8.79/100000 (male 10.23/100000 and female 7.31/100000). The age-standardized mortality rate by Chinese population census (ASRC) in 2000 was 7.59/100000. The mortality rates of colorectal cancer displayed a significant increasing trend in Hebei Province from 1973-1975 to 2010-2012, with an increased rate of 28.03%. In Cixian County, the annual percentage change (APC) of colorectal cancer incidence rate was 3.55, while the APC of colorectal cancer mortality rate was 1.64 for males from 1988 to 2012. In Shexian County, the APC of colorectal cancer incidence rates were 4.68 and 9.17 for males and females from 2000 to 2012, respectively;the APC of colorectal cancer mortality was 5.61 for males in Shexian County. Conclusion: The incidence and mortality rates of colorectal cancer showed an increasing trend in Hebei Province over the past 40 years. It is an important task that colorectal cancer screening is strengthened to reduce morbidity and mortality of the colorectal cancer in Hebei Province.

Clearance effect of milk containing anti-Helicobacter pylori specific antibody:a randomized clinical trial / 中国免疫学杂志

Objective:To compare and observe the different clearance effect of milk containing anti-Helicobacter pylori specific antibody. Methods:Four H. pylori strains were used to immune dairy cows to obtain milk containing anti-Helicobacter pylori specific antibody,of which,one was standardized strain and the other three were locally epidemic. Totally 148 people were screended,in which 72 were C-14 urea breath test positive, finally 39 meet the criteria. They were divided into two groups, the test group contained 21 subjects,were treated milk containing anti-Helicobacter pylori specific antibody;the 18 subjects in control group with common milk. The study was continued for 2 months. Results:Conducting the C-14 urea breath test,9 subjects in test group were negative,but no one was changed in control group. The effective clearance rate of the test group was 42. 86%,and there was no effective clearance in the control group,so there was significant difference in the two groups(P=0. 005,P<0. 05). Conclusion: The milk containing anti-Helicobacter pylori specific antibody is polyclonal and has higher valence,and could clear H . Pylori effectively.

MiR-200c/141 methylation inhibits the expression of miR-200c and miR-141 in gastric cancer / 中国肿瘤临床

Objective:This work aims to detect the levels of miR-200c/141 methylation and miR-200c/141 in gastric cancer tissue and investigate the relationship between miR-200c/141 expression and clinical parameters. Methods:The methylation status of miR-200c/141 CpG island and miR-200c/141 in gastric cancer tissue specimens was evaluated by qRT-PCR or BS-MSP method. We analyzed the relationship among the methylation status of miR-200c/141 CpG island, expression level of miR-200c or miR-141, and clinical parame-ters. Results:The status of miR-200c/141 CpG island methylation in gastric cancer tissue was significantly higher compared with that in paracarcinoma tissue. MiR-200c and miR-141 were markedly decreased in gastric cancer tissue compared with those in adjacent tis-sue. MiR-200c/141 CpG island methylation was negatively related with the expression of miR-200c and miR-141 in gastric cancer speci-mens. Conclusion:The upregulation of miR-200c/141 CpG methylation inhibits miR-200c/141 expression in gastric cancer tissue.

Expression and correlation of tumor-associated macrophages and CCL5 in ganstric cancer / 中国免疫学杂志

Objective:To study the expression and correlation of tumor-associated macrophages(TAM) and CCL5 in ganstric cancer.Methods:48 cases patients with completed clinical and pathological data of gastric cancer paraffin block specimens were select-ed.Cancer tissues and adjacent tissues were used as control,using SP immunohistochemical method to detect CD68 and CCL5 in gastric cancer tissues and adjacent tissues,and using the Spearman correlation statistics statistical methods for the correlation.Results:CD68 and CCL5 showed positive expression in gastric cancer tissue,significantly higher than those in the adjacent tissues(P<0.01),CD68 and CCL5 were related with gastric cancer invasion depth, lymph node metastasis, TNM stage and tumor differentiation ( P<0.001 ) . There was positive relation between the expression of CD68 and CCL5 in gastric cancer(P<0.01,r=0.759).Conclusion: CD68 and CCL5 played a driving role to the invasion and metastasis of gastric cancer occurrence,suggesting that the secretion CCL5 by TAM may promote the invasion and metastasis of gastric cancer.

Incidence and mortality of cancers appeared in the Hebei provincial cancer registry system in 2011 / 中华流行病学杂志

Objective To analyze the cancer incidence and mortality in Hebei cancer registry available areas in 2011.Methods Data were collected from 8 population-based cancer registries systems in Hebei province.Incidence and mortality rates stratified by areas (urban/rural),sex,age group and cancer site were analyzed.10 common cancers in different groups,proportions and cumulative rates were calculated.The Chinese population census in the year 2000 and Segi's populations were used for age-standardized incidence/mortality rates.Results In all the 8 cancer registries that covering a total of 4 573 293 population (2 139 779 in urban and 2 433 514 in rural areas),data was used for the analysis.The total new cancer incidence cases and deaths were 11 269 and 7 477,respectively.All the morphologically verified cancer cases (MV％) accounted for 75.26％ while 3.85％ of the incident cases were identified only through death certification records (DCO％).The mortality to incidence ratio appeared as 0.66.The crude incidence appeared in the Hebei cancer registration areas was 246.41/105 (264.55/105 in males and 227.75/105 in females).The age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) appeared as 207.13/105 and 206.61/105 respectively,with the cumulative incidence rates as (0-74 age years old) 23.57％.The cancer incidence and ASIRC were 242.64/105 and 200.19/105 in urban areas,whereas 249.72/105 and 214.11/105,respectively in rural areas.The crude mortality in Hebei cancer registration areas was 163.49/105(196.54/105 in male,129.51/105 in female),with age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) as 144.48/105 and 147.69/105.The cumulative mortality rate (0-74 age years old) was 14.71％.The cancer mortality (167.91/105) in rural areas seemed higher than the mortality (158.47/105) in urban areas.The most common sites of cancers were:stomach,lung,esophagus,breast,liver and colorectal,which accounted for 71.66％ of all the cancer cases.Lung cancer,stomach cancer,esophagus cancer,liver cancer and colorectal cancer were the major causes responsible for the cancer deaths in the areas with data of cancer registration,which accounted for 74.79％ of all the cancer deaths.Conclusion The coverage of Hebei cancer registration population could reflect the cancer burden in various areas and populations.The most commonly seen cancers were stomach,lung,esophagus,breast,liver,and colorectal,in Hebei province.In order to reduce the burden of cancers,prevention and control measures should be strengthened.

Incidence rates of cancer among registered residents of urban Shijiazhuang in 2012 / 中国肿瘤临床

Objective:To study the incidence rates of cancer in the urban area of Shijiazhuang city, China in 2012 based on the data of 2,374,827 registered residents. Methods: The incidence of diagnosed cancer cases in 2012 was obtained from the hospital reimbursement database of the medical insurance center of the city by retrieving the records on first-time reimbursement applications for the hospitalization of tumor patients from January 1 to December 31 in 2012. Population census data was obtained from the Population Department of the Shijiazhuang Public Security Bureau. The site-specific and sex-specific age-adjusted incidence rates were calculated. Results:The overall incidence rate, the age-adjusted rate of the Chinese population (ASRC), and the age-adjusted rate of the world population (ASRW) for both men and women were 237.53, 129.86, and 167.71 per 100,000 individuals, respectively. The incidence rate increased with age and peaked in the 75-79 years age groups of men and women at 1,729.42 and 867.35 per 100,000 individuals, respectively. The top ten most frequently diagnosed cancers in males were lung, stomach, colorectal, liver, esophagus, kidney, prostate, leukemia, bladder, as well as lymphoma, whereas those in females were the breast, lung, colorectal, stomach, cervical, uterine body, ovary, lymphoma, esophageal, and liver cancers. The incidence rate and ASRW of all cancers combined in men were 269.05 and 187.52 per 100,000 individuals, whereas those for women were 207.57 and 150.44 per 100 000 individuals, respectively. Compared with the average incidence rates of 31 Chinese cities in 2009, the ASRW of lung, stomach, and colorectal cancers in males from Shijiazhuang was nearly equal to the national level;however, the ASRW of breast cancer in females from Shijiazhuang was higher than the national level. When the incidence rates of Shijiazhuang in 2012 were compared with those of Beijing in 2009, the ASRW of stomach and esophageal cancers in men of Shijiazhuang was twice that of the same cancers in Beijing. However, the same parameters for the pancreatic and prostate cancers in men, as well as the thyroid and uterine body cancers in women of Beijing, were twice the values for Shijiazhuang. Conclusion: The ASRWs of the major types of cancer, such as the lung, stomach, colorectal, and breast cancers, in urban Shijiazhuang in 2012 were identical to those of the 31 Chinese cities in 2009. Compared with Beijing, the incidence rates of pancreatic, prostate, and thyroid cancers were significantly higher in Shijiazhuang, whereas those of esophageal and stomach cancers were significantly lower.

Effects of Periplocin from Cortex Periplocae on Apoptosis of Human Lung Cancer A549 Cells and Expression of Survivin / 医药导报

Objective To investigate the effects of periplocin from Cortex Periplocae (CPP) on apoptosis of human lung cancer A549 cells and expression of survivin, and demonstrate its anti-tumor effect and the possible mechanism. Methods Inhibitory effect of CPP at different concentrations (1. 25, 2. 50, 5. 00, 10. 00, 20. 00 ng·mL-1 ) and for different time length (24, 48, 72 h) on A549 cell proliferation was tested by MTT method. Apoptosis rate of A549 cells treated with CPP at different concentrations (2. 50, 5. 00, 10. 00 ng·mL-1 ) were measured using flow cytometry (FCM) for 6, 12, 24, 48, 72 h, respectively. The morphological and ultrastructural changes of the apoptosis cells were observed by acridine orange/ ethidium bromide (AO/ EB) staining and transmission electron microscopy (TEM). The effects of CPP on mRNA and protein expression of apoptosis associated gene survivin were assessed by RT-PCR and Western blotting. Results CPP could significantly inhibit the growth of A549, and the inhibition rate reached (93. 46±2. 35)% . The results of FCM showed that the apoptosis rate of A549 cells treated with CPP was increased significantly as compared to the control group ( P<0. 05). Meanwhile, typical apoptotic peaks were detected. The characteristic morphological changes of apoptosis were observed in A549 exposed to CPP, including cell shrinkage, the nuclei became yellow-red by AO/ EB staining, and typical ultrastructural changes, including nuclear chromatin condensation along the nuclear membrane, vacuolar degeneration of cytoplasm observed by TEM. The result of RT-PCR indicated that survivin mRNA expression decreased obviously in A549 cells exposed to CPP. The protein expression of survivin in A549 cells treated with 10. 0 ng·mL-1 CPP(0. 251±0. 012)was weaker than that in control group(0. 928±0. 016). Conclusion CPP can induce apoptosis in human lung cancer cell lines A549, and the probable mechanism is related to the down-regulation of survivin mRNA and protein.

Effects of FSEER on immunosuppressive and bone-marrow-suppressive mice after chemotherapy / 中国免疫学杂志

Objective:To observe the effect of FSEER on the immunosuppressive and bone-marrow-suppressive mice after chemotherapy,and explore the mechanism of hematopoietic and immunologic function in mice accentuated by FSEER.Methods: Mice were injected cyclophosphamide(Cy)except control group,then randomly divided into mode group(saline),FSEER groups[120,60 mg/( kg· d) ].The spleen index( SI) of all mice was calculated respectively.Flow cytometry instrument testing mice peripheral blood lymphocytes CD3,CD4,CD8 change.The content of TNF-α,IL-2 and IL-12 in mice serum were measured by ELISA kits.Morphological images of bone marrow of the mice were observed under the microscope after Wright-Giemsa′s staining.Results:The spleen index( SI) was increased in both of the two FSEER groups.ELISA analyses showed that the content of TNF-αand IL-2 was increased in both of the two FSEER groups.The population of CD3+CD4+T lymphocyte and the ratio of CD4+/CD8+were all increased in the low dose experimental group.After treated with FSEER, the hematopoietic depression was improved significantly.Conclusion: FSEER can improve the state of immunosuppressive and myelosuppressive mice caused by Cy thus could alleviate the side effect of chemotherapy ef-fectively.

Inhibitory Effects of Periplocin from Cortex Periplocae on Human Lung Cancer Cell Line QG56 / 天津医药

Objective To investigate the inhibitory effects of periplocin from cortex periplocae (CPP) on human lung cancer cell line QG56 and to discuss its mechanism. Methods QG56 cells were cultured in vitro. The final concentrations of CPP in control group were 1.25, 2.50, 5.00, 10.00 and 20.00μg/L. QG56 cells were treated with ascending concentration of CPP for 24 h, 48 h and 72 h. The cell proliferation was measured using MTT method. The morphological changes of QG56 cells were observed under inverted microscope. Flow cytometry (FCM) was used to detect the effects of CPP on cell cycle and cell apoptosis. The expression of apoptosis associated gene bax mRNA in QG56 cells was detected by RT-PCR. The expres-sion of bax protein before and after treatment of CPP was examined by SP immunocytochemistry. Results The inhibitory ef-fect of CPP on the proliferation of QG56 cells was increased with the increasing concentrations of CPP and the prolonged du-ration of treatment. The morphological changes were displayed in QG56 exposed to CPP. The results of FCM showed that CPP caused cell cycle arrest at G0/G1 phase. The apoptotic rate of QG56 cells was significantly increased after CPP treatment for 48 h (P<0.05). The expression of bax mRNA was increased in QG56 exposed to CPP. The result of immunocytochemis-try indicated that CPP up-regulated the expression of bax protein. Conclusion CPP showed significant inhibitory effect on human lung cancer cell lines QG56 through inducing cell cycle arrest and apoptosis.

Effect of costimulatory molecule B7-H3 on the biological characteristics of esophageal cancer Eca-109 cell line / 中国癌症杂志

Background and purpose:Esophageal cancer is a serious disease threatening human health, and it is very difficult to understand the development mechanism and find the therapeutic methods for esophageal cancer. In recent years, B7-H3, as a new member of B7 immunoregulatory superfamily, overexpressed in multiple tumor types, is considered to be a new tumor marker and potential therapeutic target. This study aimed to detect the expression of B7-H3 in esophageal cancer cell lines TE-1, TE-13, Eca-109 and exploring the effect of B7-H3 siRNA on cell proliferation, migration and invasionin vitro in human esophageal cancer Eca-109 cell line. Methods:The expression of B7-H3 in esophageal cancer cell lines TE-1, TE-13 and Eca-109 were detected by reverse transcription polymerase chain reaction (RT-PCR). B7-H3 siRNA and control siRNA were transfectedin vitro into human esophageal cancer Eca-109 cells using LipofectamineTM 2000. The expressions of B7-H3 mRNA and protein in Eca-109 cells were analyzed by RT-PCR and Western blot. The proliferation, migration and invasion abilities of Eca-109 cells were measured by MTT assay, wound scrape assay and transwell invasion assayin vitro,respectively.Results:All tested cultured esophageal cancer cell lines constitutively expressed B7-H3 mRNA under normal conditions (TE-1 0.382±0.008, TE-13 0.399±0.008, Eca-109 0.428±0.012). After transfection, the expression of B7-H3 mRNA levels decreased in B7-H3 siRNA transfected group, compared with control siRNA transfected group (0.128 5±0.000 2vs 0.532 4±0.000 7,P0.05).Conclusion:All tested esophageal cancer cell lines constitutively express B7-H3 mRNA. B7-H3 siRNA interference inhibits Eca-109 cell migration and invasion abilities. B7-H3 may have a critical role in regulating Eca-109 cell progression.

Effect of IL-18 on expression of molecule on surface of 9 L in vitro and in vivo / 中国免疫学杂志

Objective:To explore the influence of IL-18 on the expression of MHCⅠ,MHCⅡ,CD80,CD86 on the surface of 9L cells,to identify the effect of IL-18 on the immunogenicity and the efficiency of tumor antigen presentation of 9L.Methods:Retroviruses were used to transduce the mIL-18 gene into rat glioma cells and the cell clones (9L/IL-18) which steadily expressing mIL-18 gene were obtained ,and got the control cells of 9L/LXSN by the same method.The expression of MHCⅠ,MHCⅡ,CD80,CD86 on the cell surface were assessed by flow cytometry.The cell suspension of 9L/IL-18,9L/LXSN and 9L cells were inoculated into the brain of F344 rat to establish the animal models by the stereotactic technique ,got the tumor tissues to analyze the expression of MHCⅠ, MHCⅡ,CD80 and CD86 on the surface of tumor cells after 14 days.Results:The expression of MHCⅠ,MHCⅡ,CD80 and CD86 on the surface of 9L/IL-18 were (10.9±1.44)%,(0.61±0.14)%,(1.01±0.14)%,(0.57±0.11)% ; had no significant differences with the others in vitro (P>0.05);while the expression of MHCⅠ,CD80 and CD86 on the surface of 9L/IL-18 were(67.51± 1.40)%,(12.51±1.57)%,(6.95±0.56)%which were higher than 9L/LXSN and 9L cells (P0.05) in vivo.Conclusion: IL-18 did not affect the immunogenicity of 9L in vitro,but improve the immunogenicity and tumor antigen presentation in vivo.

The expression and significance of SDF-1/CXCR4 biological axis in laryngeal squamous cell carcinoma and lymph node metastasize / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the correlation between the stromal cell-derived factor (SDF-1) and the receptor fusin (CXCR4) in carcinoma of larynx, and investigate some mechanisms of SDF-1/CXCR4 during the development, invasion and lymph node metastasis of laryngocarcinoma.@*METHOD@#Detecting the expression of SDF-1 and CXCR4 by immunohistochemical method (SP) in laryngocarcinoma, paraneoplastic tissues, normal laryngeal mucosa and cervical lymph node. Using Kruskal-Wallis H test, chi2 test, Spearman rank correlation analysis and so on to do statistical analysis.@*RESULT@#The positive expression rate of SDF-1 and CXCR4 in laryngocarcinoma was obviously higher than in paraneoplastic tissues and normal laryngeal mucosa tissues (P < 0.01). And the expression of two proteins was correlated with lymph node metastasis (P < 0.01), clinical stage (P < 0.01) and pathological grading of tumor (P < 0.05). The positive expression rate of SDF-1 and CXCR4 protein in metastasis lymph node tissue was higher than that in non metastasis lymph node tissue (P < 0.01). The expression of SDF-1 is correlated positively with the expression of CXCR4 in laryngocarcinoma.@*CONCLUSION@#SDF-1 and CXCR4 protein are highly expressed in laryngocarcinoma and in metastasis lymph node tissue. And they are correlated with lymph node metastasis, clinical stage and pathological grading of the tumor. According to the results, the two proteins may relate to infiltration and metastasis of laryngeal squamous cell carcinoma and play a role of synergistic action in the development and invasion of carcinoma of larynx.

Evaluation on ischemia-modified albumin, D-dimer and cTn Ⅰ in the early diagnosis of acute coronary syndrome / 中华检验医学杂志

ObjectiveTo investigate the early diagnosis value of IMA and D-dimer and cTn Ⅰ in ACS.MethodsAll the 113 blood samples of patients with chest pain in the emergency department of the Third Hospital of Hebei Medical University were selected.Thirty healthy people were selected as the control group.Patients were divided into two groups:one of 52 cases was within 3 hours after onset of chest pain.the other of 61 cases was between 3 to 6 hours.According to the final clinical diagnosis,31 cases were divided into non-ischemic chest pain group (NICP) and 82 cases were divided into the ACS group.The ACS group was divided into the UA group (51 cases),NSTEMI group (18 cases) and STEMI group (13 cases).IMA was measured with albumin-cobalt binding test,and D-dimer was measured with the automated blood coagulation analyzer,and cTn Ⅰ was measured with the automatic biochemical analyzer.Levels of IMA,D-dimer,cTn Ⅰ were compared in the different groups and their sensitivity,specificity and accuracy to the early diagnosis of ACS were evaluated by Four format diagnositic test.ResultsThe levels of IMA in ACS group,which include the UA group,NSTEMI group and STEMI group were (0.722 ± 0.181 ),(0.601 ± 0.122),(0.631 ± 0.153 ) ABSU respectively.The levels of D-dimer were ( 0.485 ± 0.124 ),( 0.571 ± 0.181 ),(0.748 ± 0.094 ) mg/L respectively.The levels of cTn Ⅰ were ( 0.076 ± 0.027 ),( 0.059 ± 0.038 ),(0.065 ± 0.015 )μg/L respectively.Concentrations of IMA,D-dimer and cTn Ⅰ in ACS group were significantly higher than those of the NICP group [IMA (0.338 ± 0.065 ) ABSU,D-dimer (0.368 ± 0.078 )mg/L,cTn Ⅰ (0.022 ±0.007) μg/L] and the controls group [IMA (0.292 ±0.058) ABSU,D-dimer (0.267 ±0.052) mg/L,cTn Ⅰ (0.029 ± 0.016) μg/L].There were significant differences between the ACS group and the NICP group and the control group,F value was 3.613,3.289 and 3.521 respectivily,and P ＜0.05.The levels of IMA in ACS group within 3 hours and between 3 to 6 hours,which is (0.665 ±0.104 ),(0.520 ± 0.073 ) ABSU,were significantly higher than that of the controls (0.292 ± 0.058 ) ABSU ( F value was 3.58,P ＜ 0.05 ).The levels of D-dimer and the cTn Ⅰ in the group between 3 to 6 hours [which were (0.634 ±0.213 ) mg/L and (0.079 ±0.032) μg/L] were significantly higher than those of the controls [(0.267 ±0.052) mg/L and (0.029 ±0.016) μg/L] (q was4.24 and 3.46,P ＜0.05).The sensitivity,specificity and accuracy was 83.36％,70.97％ and 81.42％ of the IMA in a separate diagnosis of ACS,but the sensitivity,specificity and accuracy were 97.56％,58.06％ and 86.73％ of the IMA,D-dimer and cTn Ⅰ with the affiliation diagnosis.ConclusionThe serum IMA is a more sensitive indicator of ACS in early myocardial ischemia than cTn Ⅰ and plasma D-dimer.Serum IMA in combination with D-dimer and cTn Ⅰ could improve the sensitivity and specitivity,and had value to guide cinical diagnosis of ACS in the early stage.

Interleukin-27 signal pathways and tumor / 国际肿瘤学杂志

Interleukin (IL)-27 is a new member of the IL-6/IL-12 family composed of p28 subunit and Epstein-Barr virus induced gene 3 (EBI3) subunit. Its receptor is composed of WSX-1 and gp130. It has dual properties including pro-inflammatory and anti-inflammatory function at different conditions. Studies have shown that IL-27 exerts its biological activities through stimulating JAK1/STAT1, JAK1/STAT3 signal pathways and regulating the production of Th1, Th17 as well as their related-cytokines. Furthermore, IL-27 can exert the role of anti-tumor activity by enhancing the effect of cytotoxic T cells and anti-angiogenesis.

Effects of celecoxib on tumor growth and cell apoptosis in human triple-negative breast cancer xenografts in nude mice / 肿瘤研究与临床

Objective To evaluate the effects of celecoxib on tumor growth and cell apoptosis in human triple-negative breast cancer (TNBC) xenografts in nude mice.Methods Human TNBC MDA-MB-231 cells were inoculated subcutaneously into BALB/c nude mice.The mice (n=32) were then randomly divided into 4 groups,the control group and the celecoxib group (receiving 25,50,100 mg·kg-1·d-1 respectively).At the end of the study,tumor tissues were collected and tumor volume was measured.Cell apoptosis was determined by flow cytometry (FCM) analysis.NF-κB p65 and pS0 protein levels were measured by immunohistochemistry.Caspase-3 and survivin protein levels were detected by western blotting.Results celecoxib at dose of 25,50 and 100 mg·kg-1·d-1 inhibited the tumor growth significantly,compared with the control group.FCM results showed that apoptotic rates were (13.58±3.16) ％ and (21.91±4.75) ％ in moderate and high dose of celecoxib-treated group,compared with (3.15±1.73) ％ in control group (t =6.736,P ＜ 0.05;t =12.151,P ＜ 0.05).p65 expressions were 79.3 ％,46.7 ％ and 23.9 ％ in low,moderate and high dose of celecoxib-treated group,compared with 89.7 ％ in control group (x2 =3.312,P ＜ 0.05; x2 =10.785,P ＜ 0.05;x2 =15.900,P ＜ 0.05).Besides,western blotting analysis demonstrated that celecoxib significantly downregulated survivin expression,while upregulated the active form of caspase-3 expression.Conclusion Celecoxib could suppress TNBC tumor growth and induce cell apoptosis,which might be partially associated with inactivation of p65 and downregulation of survivin.