Relationship between expression of caveolin-1 and pERK1/2 and prognosis in non-small cell lung cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the relationship between expression of caveolin-1 (Cav-1) and pERK1/2 and prognosis in non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Cav-1 and pERK1/2 protein expression was assessed by immunohistochemistry in samples obtained from 160 patients with NSCLC and 20 patients with normal lung tissue.</p><p><b>RESULTS</b>Normal bronchial and alveolar epithelial cells were positive for Cav-1 (membranous and cytoplasmic staining patterns). The expression rate of Cav-1 in NSCLC was 65.6% (105/160), which was significantly lower than that in normal lung tissue (P = 0.002). The Cav-1-positive rates in well to moderately differentiated tumors and poorly differentiated tumors were 56.8% (46/81) and 75.7% (53/70), respectively (P = 0.015). The expression of Cav-1 was much higher in patients with lymph node metastasis (77.8%, compared with 55.7% in lymph node-negative group, P = 0.003). The expression was also higher in stage III to IV than in stage I to II disease (75.4%, compared with 58.2%, P = 0.024). The overall survival of patients with Cav-1-positive tumors (71.4%, 37.1% and 17.1% 1-, 3- and 5-year survival, respectively) was lower than those with Cav-1-negative tumors (89.1%, 69.1% and 43.6% 1-, 3- and 5-year survival, respectively, P = 0.000). On the other hand, normal bronchial and alveolar epithelial cells were negative for pERK1/2. The expression rate of pERK1/2 in NSCLC was 61.3%, which was significantly higher than that in normal lung tissues (P = 0.000). The pERK1/2-positive rates in well to moderately differentiated tumors and poorly differentiated tumors was 53.1% and 71.4%, respectively (P = 0.021). The expression of pERK1/2 was much higher in patients with lymph node metastasis (80.6%, compared with 45.5% in lymph node-negative group, P = 0.000). The expression of pERK1/2 was also higher in stage III to IV than in stage I to II disease (76.8%, compared with 49.5%, P = 0.426). The overall survival of patients with pERK1/2-positive tumors (74.5%, 42.9% and 19.4% 1-, 3- and 5-year survival, respectively) was lower than those with pERK1/2-negative tumors (82.3%, 56.5% and 37.1% 1-, 3- and 5-year survival, respectively, P = 0.002). Cav-1 and pERK1/2 expression showed negative correlation (P = 0.000).</p><p><b>CONCLUSIONS</b>Cav-1 expression is lower in NSCLC than in normal lung tissue, whereas pERK1/2 expression is higher in NSCLC. Positive expression of Cav-1 and overexpression of pERK1/2 correlates with tumorigenesis and tumor progression of NSCLC. Cav-1 and pERK1/2 may serve as potential markers for predicting prognosis in NSCLC.</p>

Relationship of ezrin protein expression to the carcinogenesis and prognosis of infitrating breast ductal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship of ezrin protein expression to the carcinogenesis and prognosis of infiltrating breast ductal carcinoma.</p><p><b>METHODS</b>S-P immunohistochemical staining was used to detect the ezrin protein expression in 88 patients with infiltrating ductal carcinoma, and in 54 patients with intraductal hyperplastic lesions of the breast. The clinicopathological data and follow-up information of these patients were all obtained. The relationship of ezrin protein expression to the clinicopathological parameters and the prognostic significance in the infiltrating breast ductal carcinoma was analyzed using Chi-square test (chi2), Kaplan-Meier and Cox models.</p><p><b>RESULTS</b>The immunohistochemical staining results showed that the strong positive expression rate of ezrin protein in the normal ductal epithelium, simple ductal hyperplasia, atypical hyperplasia and infiltrating ductal carcinoma of the breast was 9.1%, 16.7%, 43.3% and 64.8%, respectively, which was significantly higher in atypical hyperplasia and infiltrating ductal carcinoma than that in the normal ductal epithelium and simple ductal hyperplasia (P < 0.05). The strong ezrin protein expression in the infiltrating ductal carcinoma was positively correlated with axillary lymph node metastasis, histological differentiation grade, TNM stage and CD44v6 expression, but negatively correlated with the expression of E-cadherin (P < 0.05). It was also found that the survival of the patient with strong positive expression of ezrin protein was significantly shorter than that of the control (P < 0.05).</p><p><b>CONCLUSION</b>Ezrin protein may play an important role in the carcinogenesis of infiltrating breast ductal carcinoma. The strong expression of ezrin protein may be used as a biomarker for predicting poor prognosis in the patients with infiltrating breast ductal carcinoma.</p>

Analysis of the changing trends of frequency and localization of gastric cancers arising from different sites of the stomach in population of the high incidence area of esophageal and gastric cancers in Hebei province / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the changing trends of frequency and localization of gastric cancers arising from the gastric cardia, corpus and antrum during the past 14 years in population of the high incidence area of esophageal and gastric carcinoma in Hebei province, China.</p><p><b>METHODS</b>The clinicopathological data of 4334 cases of gastric carcinomas among the local residents of Cixian and Zanhuang counties, initially diagnosed in our department from 1993 to 2006, were retrospectively analyzed. The proportion of gastric carcinomas arising from the gastric cardia, corpus and antrum in different years and in patients with different sex and ages were analyzed and compared, and the changing trends of the frequency of gastric carcinoma arising from different sites of the stomach were statistically analyzed.</p><p><b>RESULTS</b>Among all the 4334 gastric carcinomas, gastric cardia carcinoma accounted for 68.0%, significantly higher than that of corpus (24.2%) and antrum (7.9%; chi(2) = 124.396, P < 0.0001). An increasing tendency in the proportion of gastric cardia carcinoma from 1993 to 2006 was seen. The percentage of cardiac carcinoma in the high incidence area of esophageal carcinoma (Cixian county) was higher than that in the high incidence area of gastric cancer (Zanhuang county) (71.2% vs. 51.2%; chi(2) = 109.648, P < 0.0001). The increase in the incidence of cardiac carcinoma in Cixian county was mainly due to the increase of cardiac carcinoma from 1993 to 2006, while the contributing factor for the increase in the proportion of cardiac carcinomas was resulted from the decrease of incidence of antrum carcinoma in Zanhuang county during the same period. The occurring site of gastric carcinoma was related with age of patients (chi(2) = 58.380, P < 0.0001). The percentage of carcinoma of the gastric body was highest in < 50 year age group, while that in the gastric cardia was highest in 61 - 70 year age group (71.6%).</p><p><b>CONCLUSION</b>The major occurring site of gastric carcinoma is the gastric cardia among the local residents in population of the high incidence areas of esophageal and gastric carcinomas during the past 14 years in Hebei province, China. The increasing trend of cardiac carcinoma and decreasing trend of corpus carcinoma in Cixian county and antrum carcinoma in Zanhuang county will be maintained in the coming years if the epidemiological conditions will not be changed.</p>

Studies on the cut-off value of serum pepsinogen abnormality for screening chronic atrophic gastritis and gastric carcinoma / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the fast serum pepsinogen level of the healthy adults among local population in areas with high incidence of gastric cancer and to study the suitable cut-off values of serum pepsinogen abnormality for the screen of chronic atrophic gastritis (CAG) and gastric carcinoma (GC) in China.</p><p><b>METHODS</b>Serum PG I and PG II levels were detected with time resolved fluorescence immunoassay (TRFIA). The fast serum PG I and PG I level as well as PG I/PG II ratio of 606 healthy adult residents among local population in Zanhuang county, Hebei province were detected and the normal distribution ranges determined. The relationship between different cut-off values of serum PG I level, PG I/PG II ratio and corresponding pathological changes in gastric mucosae were comparatively analyzed with serum PG detection, endoscopic biopsy and pathological observation in 720 cases of local residents receiving endoscopic examination in the high incidence area of gastric cancer. The efficacy, sensitivity and specificity of different PG I, PG II abnormality cut-off values in the screen p rogram of CAG and GC were statistically analyzed.</p><p><b>RESULTS</b>The serum PG I, PG II and PG I/PG II ratio levels of healthy adults from a local natural population in the high incidence area of gastric cancer were all skewed from normal distribution. The median level of PG I, PG II and PG I/PG II were 161 microg/L, 14.8 microg/L and 10.5 respectively. Data from comparative studies on serum PG level and pathological changes of gastric mucosae showed that within the serum PG I range from 40 microg/L to 80 microg/L and PG I/PG II ratio range from 3 to 8, sensitivity of the screening program for CAG and GC increased while the specificity decreased along with the increase of cutoff values of serum PG I and PG I/PG II ratio. Results from statistical receiver operator characteristic curve (ROC) analysis suggested that the best cut-off value of PG I and PG I/PG II abnormality for the screening of CAG and GC being PG I < or =60 microg/L,PG I/PG II < or =6 respectively.</p><p><b>CONCLUSION</b>The serum PC I, PG II and PG I/PG II ratio levels of healthy adults from a local natural population in the high incidence area of gastric cancer were all skewed from normal distribution. Serum PG I < or =60 microg/L and PG I/PG II ratio < or =6 as abnormal cut-off value for the screen of CAG and GC could result relatively good sensitivity and specificity.</p>

Correlation of serum pepsinogen level and gastric mucosal changes of residents in the high incidence area of gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the correlation between serum pepsinogen (PG) level and gastric mucosal changes of the residents who live in the high incidence area of gastric cancer, and investigate the value of serum PG level in screening for chronic atrophic gastritis (CAG) and gastric cancer (GC).</p><p><b>METHODS</b>Serum PG level was detected with time resolved fluorescence immunoassay (TRFIA). The correlation between serum PG level and gastric mucosal changes was analyzed through endoscopic biopsy and pathological examination in 720 adult residents.</p><p><b>RESULTS</b>The median serum PG I, PG II level and PG I / PG II ratio in 30 healthy residents with normal gastric mucosa was 172.0 microg/L, 9.6 microg/L and 17.5, respectively. The median serum PG I level of GC patients was significantly lower than that of chronic gastritis patients, gastric ulcer (GU) patients and local healthy residents (P < 0.05). The median PG I level of GU patients was significantly higher than that of the healthy resident group and the other groups (P <0.05). Serum PG II level in CAG, GC and GU groups were all significantly higher than that in CSG and healthy resident group (P <0.05). The PG I/PG II ratio in CAG or GC patients was significantly lower than that in the other groups (P < 0.05). The sensitivity and specificity of serum PG I < or = 60 microg/L for screening CAG or GC was 19.7% and 95.5% respectively, which were 34.7%, 89.3% for PG I/PG II < or =6, and 14.1%, 97.3% for PG I < or =60 microg/L + PG I /PG II < or =6. None in GU group was found to have serum PG I < or =60 microg/L. The median serum PG I level and PG I /PG II ratio in chronic gastritis (including CSG and CAG) with intestinal metaplasia were significantly lower than that of healthy resident group (P < 0.05). The sensitivity and specificity for screening of intestinal metaplasia were 16.6% and 92.9% by PG I < or =60 microg/L; 25.6% and 80.4% by PG I/PG II < or =6; 11.9% and 93.9% by PG I < or =60 microg/L + PG I/ PG II < or = 6.</p><p><b>CONCLUSION</b>Serum pepsinogen level of the residents in the high incidence area of gastric cancer is closely correlated with the pathological changes of gastric mucosa. Though the sensitivity of serum pepsinogen level is relatively lower in the screening for chronic gastritis, gastric cancer and intestinal metaplasia, the specificity was quite high. PG I < or = 60 microg/L may be usful in differential diagnosis of gastric cancer from gastric ulcer.</p>

Effects of vitamin C on apoptosis and proliferation inhibition of human peripheral blood mononuclear cells induced by deoxynivalenol in vitro / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the effects of Vitamin C (Vit C) on the apoptosis and proliferation inhibition of human peripheral blood mononuclear cells (HPBMCs) induced by deoxynivalenol (DON) in vitro.</p><p><b>METHODS</b>The effects of Vit C pretreatment at different dosages (25 micromol/L and 100 micromol/L) on apoptosis, apoptosis related genes expression and proliferation inhibition of HPBMCs induced by DON were evaluated with cell culture, flow cytometric DNA analysis and Western blotting.</p><p><b>RESULTS</b>Flow cytometry (FCM) analysis showed that the apoptosis rate of HPBMCs in 2000 microg/L DON group was (28.82 +/- 1.67)%, which was significantly higher than that in control group (14.07 +/- 0.70, P < 0.05). Compared with DON group, the apoptosis rate of HPBMCs in 25 micromol/L Vit C pretreatment group was significantly decreased (28.82 +/- 1.67)% vs (22.39 +/- 1.05)%, P < 0.05, while that in 100 micromol/L Vit C pretreatment group was obviously increased (36.07 +/- 2.92)%, P < 0.05. Western blotting analysis showed that the expression of Bax and Caspase-3 up-regulated by DON was markedly decreased, while the expression of Bcl-2 down-regulated by DON was increased by 25 micromol/L Vit C pretreatment (P < 0.05). 100 micromol/L Vit C pretreatment could further increase the expression of Bax and Caspase-3 of HPBMCs induced by DON, while no significant effects on the Bcl-2 expression induced by DON were seen. FCM analysis showed that the proliferation index of HPBMCs in Vit C pretreatment groups at different dosages was all dramatically increased as compared with that in DON groups (P < 0.05).</p><p><b>CONCLUSION</b>25 micromol/L Vit C pretreatment could at certain extent inhibit the apoptosis and reverse the abnormal expression of apoptosis related genes of HPBMCs induced by DON in vitro, while 100 micromol/L Vit C pretreatment could further increase the apoptosis rate of HPBMCs induced by DON. Vit C pretreatment could reverse the proliferation inhibition of HPBMCs induced by DON in vitro.</p>

Effects of vitamin C on the inhibition of human leucocyte antigen class I (HLA-I) expression of human peripheral blood mononuclear cells induced by deoxynivalenol in vitro / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the putative effects of Vitamin C (Vit C) on inhibition of human leucocyte antigen class I (HLA-I) expression of human peripheral blood mononuclear cells (HPBMCs) induced by deoxynivalenol (DON) in vitro.</p><p><b>METHODS</b>The effects of Vit C on the changes of HLA-I expression of HPBMCs induced by DON in vitro were evaluated with cell culture, flow cytometry (FCM), Western blotting and immunocytochemical methods.</p><p><b>RESULTS</b>FCM analysis showed that HLA-I expression of HPBMCs in DON treated cells was significantly lower than that in controls (FI 0.88 +/- 0.02 vs 1.00 +/- 0.03, P < 0.05). As compared with DON group, the HLA-I expressions of HPBMCs in the two Vit C (25 micromol/L and 100 micromol/L) pretreatment groups were all significantly increased (1.15 +/- 0.06 and 1.10 +/- 0.02 vs 0.88 +/- 0.02, P < 0.05). Exposure to different dosage of Vit C alone could dramatically increase the expression of HLA-I of HPBMCs in vitro as compared with that in the normal control (FI for 25 micromol/L and 100 micromol/L Vit C treatment group was 1.28 +/- 0.03 and 1.25 +/- 0.05 respectively, P < 0.05). Immunocytochemical results showed that the percentages of HLA-I positive expression of HPBMCs in Vit C pretreatment groups at different dosages were significantly higher than those in DON group (70.10 +/- 6.90)%, (64.50 +/- 5.50)% vs (42.20 +/- 4.30)%, P < 0.05. Western blotting confirmed the results of FCM and immunocytochemistry.</p><p><b>CONCLUSIONS</b>Vitamin C pretreatment at different dosages could reverse at some extent the inhibitive effects of DON on HLA-I expression of HPBMCs.</p>

Expression and prognostic significance of survivin and caspase-3 in esophageal squamous-cell carcinoma and their relationship with HSPs expression / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the prognostic significance of expression of survivin and caspase-3 in esophageal squamous-cell carcinoma (ESCC) and the relasionship with expression of heat shock proteins 27 and 70 (HSP27 and HSP70).</p><p><b>METHODS</b>Expressions of survivin and caspase-3 in 101 cases of ESCC were quantitatively detected with flow cytometry. Their expressions in long-term survival group (group A, >or= 5 years, 38 cases) were compared with those in the short-term survival group (group B, <or= 1 year, 63 cases). Their prognostic significance and clinocopathological characteristics were evaluated and their relationship with HSP27 and HSP70 expression was analyzed.</p><p><b>RESULTS</b>The mean fluorescence intensity (mFI) of survivin in group B was 6.79 +/- 2.11, which was significantly higher than that (5.00 +/- 0.77) in group A (P < 0.01). The mFI of caspase-3 in the two groups were similar (5.12 +/- 0.67 vs. 5.07 +/- 0.77, P > 0.05). The positive expression rate of survivin in group A was significantly lower than that in group B (31.6% vs 54.0%, P = 0.029). Compared with that in short-term survival group, the strong positive expression rate of caspase-3 in long-term survival group was significantly higher (47.6% vs. 68.4%, P = 0.042). Positive expression rate of caspase-3 showed decreasing tendency with increase in age. No significant differences in clinicopathologic features in relation to expression rate of caspase-3 other than tumor length. No correlation was observed between expression intensity of survivin and any clinicopathologic features. Logistic regression analysis indicated that survivin and caspase-3 expressions were of independent prognostic significance for ESCC. There was no association between survivin and caspase-3 expression and expression of HSP27 and HSP70.</p><p><b>CONCLUSION</b>The expressions of survivin and caspase-3 are two independent prognostic factors in ESCC. They do not correlate with HSP27 and HSP70 expression.</p>

Effect of testosterone propionate on the distribution pattern of calcitonin gene-related peptide in different motoneuron pools / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effect of testosterone propionate (TP) on the distribution pattern of calcitonin gene-related peptide (CGRP) in two types of motoneuron (Mn) pools in rats.</p><p><b>METHOD</b>The double labeling of cholera toxin B subunit coupled with colloidal gold (CB-Au) retrograde identification combining with immunocytochemistry was mainly used to reveal the distribution pattern of CGRP-like immunoreactivity (CGRP-LI) and its changes in the motoneuron pools labeled by CB-Au.</p><p><b>RESULT</b>TP injected intramuscularly 28 days later significantly decreased CGRP expression in Mn pool innervating extensor digitorum longus (EDL, fast-twitch), comparing with corresponding control and castration group respectively (P < 0.001), while no significant effect on Mn pools innervating soleus (SOL, slow-twitch, P > 0.05) was observed.</p><p><b>CONCLUSION</b>EDL-Mn pool is more sensitive to testosterone propionate than SOL-Mn pool in regulating CGRP expression.</p>

Carcinogenic effects of sterigmatocystin and deoxynivalenol in NIH mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To further explore the carcinogenic activity of Sterigmatocystin (ST) and the possible synergistic carcinogenic effect of deoxynivalenol (DON) in NIH mice.</p><p><b>METHODS</b>NIH mice were randomly divided into 6 groups, 30 in each. Five groups of mice were given by gastric intubation ST 3 microg/kg, ST 30 microg/kg, ST 3 microg/kg + DON 1.5 microg/kg, ST 30 microg/kg + DON 1.5 microg/kg and DON 1.5 microg/kg respectively, 3 times a week for 24 weeks. The remaining group of mice was given normal saline accordingly, serving as control. All mice were fed with HPLC-confirmed mycotoxin-free food, analysis. The mice were killed and pathologically examined at 58th and 74th weeks.</p><p><b>RESULTS</b>No pathological changes were found in the control group of mice. Adenocarcinoma of lung was observed in 25.0%, 41.7%, 62.5%, 69.2% and 37.5% of mice given ST 3 microg/kg, ST 30 microg/kg, ST 3 microg/kg + DON 1.5 microg/kg, ST 30 microg/kg + DON 1.5 microg/kg and DON 1.5 microg/kg, respectively. In addition, dysplasia of glandular stomach was detected in 50.0%, 58.3%, 37.5%, 53.8% and 25.0% of mice similarly treated.</p><p><b>CONCLUSION</b>Oral administration of ST or DON can induce adenocarcinoma in lung and dysplasia of glandular stomach in NIH mice. There is synergistic carcinogenic effect when both ST and DON are given.</p>

Experimental lung carcinogenic in vivo study of aflatoxin G1 in NIH mice / 中华病理学杂志

<p><b>OBJECTIVE</b>Aflatoxin G1 (AFG1) is a member of the carcinogenic aflatoxin family produced by aspergillus flavus. It is a major contaminating mycotoxin in food in areas of China with high cancer incidence. The purpose of this study is to explore the carcinogenic effects of AFG1 in NIH mice.</p><p><b>METHODS</b>NIH mice were randomly divided into three groups. Two experimental groups were treated intragastrically by gavage with AFG1 3 microg/kg and AFG1 30 microg/kg respectively, 3 times a week for 24 weeks. The control group was treated with normal saline. All mice were fed with food that was free of AFGs as confirmed by HPLC analysis. The mice were weighed every week throughout the entire experiment, and then sacrificed and examined pathologically at the 58th and 74th weeks respectively.</p><p><b>RESULTS</b>Compared with control mice receiving no AFG1, bronchial epithelial hyperplasia, alveolar hyperplasia and adenocarcinoma of lung were observed in mice receiving AFG1 treatment. The incidences of bronchial epithelial hyperplasia, alveolar hyperplasia and adenocarcinoma of lung were 60.0%, 10.0% and 30.0% for mice receiving 3 microg/kg AFG1 and 28.6%, 35.7%, 42.9% for mice receiving 30 microg/kg of the toxin, respectively.</p><p><b>CONCLUSION</b>Oral administration of AFG1 can induce hyperplastic lesions and adenocarcinoma of lung in NIH mice.</p>