Association of marital status with stage and survival in patients with mycosis fungoides: A population-based study.

BACKGROUND: Previous studies have shown that marital status was associated with stages and survival in patients with melanoma or Merkel cell carcinoma. To date, the impacts of marital status on stage and survival in patients with mycosis fungoides (MF) have not been determined yet. METHODS: A total of 3375 eligible cases diagnosed from 2004 to 2015 were included from the Surveillance, Epidemiology, and End Results (SEER) database. Association of marital status with stage and survival in patients with MF was analyzed. RESULTS: Married patients were more likely to be diagnosed at T1 stage (p = 0.041). And married patients were less likely to present with lymph node involvement (p = 0.007). More favorable overall survival (p < 0.001) and cancer-specific survival (p < 0.001) were demonstrated in married patients as compared with divorced patients or widowed patients. A clinically feasible prognostic model including marital status, age, sex, race, and stage at presentation was constructed. CONCLUSION: Married marital status was associated with earlier stage at diagnosis and longer survival compared with divorced or widowed marital status in patients with MF.

Putative role of the mTOR/4E-BP1 signaling pathway in the carcinogenesis and progression of gastric cardiac adenocarcinoma.

The mammalian target of rapamycin/eukaryotic translation inititiation factor 4E binding protein 1 (mTOR/4E-BP1) transduction pathway is activated in a range of malignant cancers, but its role in human gastric cardiac adenocarcinoma (GCA) has not been well defined. The present study used western blotting and reverse transcription polymerase chain reaction (RT-PCR) to assess the expression of mTOR, 4E-BP1 and eukaryotic translation initiation factor 4E (eIF4E) at the protein and mRNA levels in 33 cases of GCA and paired adjacent normal gastric mucosal tissues. The expression of mTOR at the protein level in GCA was significantly lower than that in the corresponding normal gastric mucosa (0.296 ± 0.27 vs. 1.348 ± 0.80, P<0.05), but the ratio of p-mTOR to mTOR was significantly increased in tumor tissues (1.425 ± 1.07 vs. 0.450 ± 0.24, P<0.05). The expression of 4E-BP1 was significantly decreased in GCA compared with normal tissues (p<0.05), while the levels of phosphorylated 4E-BP1 (p-4E-BP1) were markedly increased in tumor tissues (p<0.05). The levels of phosphorylated eIF4E (p­eIF4E) were significantly higher in the tumors in comparison to the corresponding normal tissues (1.822 ± 0.63 vs. 0.997 ± 0.38, P<0.05), and the levels of p-eIF4E were closely correlated with lymph node metastasis (p<0.05). The mTOR/4E-BP1 signaling pathway is activated in GCA, with mTOR activated mainly through increased mTOR phosphorylation rather than protein overexpression.

Effects of sterigmatocystin on TNF-α, IL-6 and IL-12 expression in murine peripheral blood mononuclear cells and peritoneal macrophages in vivo.

Sterigmatocystin (ST) is a toxic metabolite mainly produced by the fungi Aspergillus nidulans and Aspergillus versicolor. ST is considered a potent carcinogen, mutagen and teratogen. However, over the past few years, it has been demonstrated that it is less acutely toxic to rodents in vivo. In this study, we evaluated the putative effects of ST on the expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-12 at mRNA levels in murine peripheral blood mononuclear cells (mPBMCs) and peritoneal macrophage cells and on the serum TNF-α and IL-6 levels in BALB/c mice. Our results show the downregulation of TNF-α, IL-6 and IL-12 mRNA expression in mPBMCs and peritoneal macrophage cells using semi-quantitative reverse transcription-polymerase chain reaction following ST treatment by intraperitoneal injection. Additionally, serum TNF-α and IL-6 levels were also decreased as shown by enzyme-linked immunosorbent assay (ELISA). These results suggest that ST contamination has negative immunomodulatory effects through the downregulation of cytokine expression and secretion.

Low-dose epirubicin inhibits ezrin-mediated metastatic behavior of breast cancer cells.

AIMS AND BACKGROUND: Overexpression of ezrin contributes to the progression and invasiveness of several human cancers; however, its role in breast cancer metastasis has not been investigated in detail. METHODS: Ezrin expression in tissue samples from patients with invasive ductal carcinoma of the breast was detected by immunohistochemistry. Ezrin expression in a breast cancer cell line was evaluated using Western blot and RT-PCR. RESULTS: Elevated expression of ezrin was associated with lymph node metastasis and poor prognosis in patients with invasive ductal carcinoma. Ezrin expression was related to the invasiveness of breast cancer cells in vitro. Low-dose epirubicin inhibited the migration of breast cancer cells in a concentration-dependent manner without promoting cytotoxicity in vitro and decreased the expression of ezrin in a concentration-dependent manner. CONCLUSIONS: Low-dose epirubicin may be antimetastatic without promoting cytotoxic effects and could serve as a target for the development of therapeutics for breast carcinoma.

Involvement of MAPK and PI3K signaling pathway in sterigmatocystin-induced G2 phase arrest in human gastric epithelium cells.

SCOPE: Sterigmatocystin (ST), a mycotoxin commonly found in foodstuff and feedstuff, has been shown to be a carcinogenic mycotoxin in animal models. Many studies showed that the high level of ST contamination in grains might be related to the high incidence of gastric carcinoma in rural areas of China. However, up to now, the potential effects of ST on human gastric epithelium cells remain largely unknown. In this study, we explored the effects of ST on cell-cycle distribution and the regulatory mechanism in immortalized human gastric epithelium cells (GES-1). METHODS AND RESULTS: The effects of ST on the cell cycle distribution of GES-1 cells were determined with flow cytometric (FCM) analysis, Giemsa staining and immunofluorescence staining, while that on the expression of related gene-Cdc25C, Cdc2, CyclinB1 and the complex of CyclinB1-Cdc2 were studied with Western blot, reverse transcription polymerase chain reaction (RT-PCR) and immunoprecipitation assay respectively. We found that ST induced GES-1 cells arrested at G2 phase by regulating the expression of Cdc25C, Cdc2, CyclinB1 and the formation of CyclinB1-Cdc2 complex. Further study suggested JNK, ERK and PI3K/AKT/mTOR pathways to be involved in the process of G2 arrest induced by ST. The specific inhibitors of JNK and ERK reversed the role of ST, whereas that of PI3K/AKT/mTOR reinforced the effect of ST on cell-cycle distribution. CONCLUSION: This study demonstrates that JNK, ERK and PI3K/AKT/mTOR pathways participated in the G2 arrest induced by ST through the deregulation of CyclinB1, Cdc2 and Cdc25C. It may play some roles in the gastric carcinogenesis in ST exposure populations.

[Construction of human TAP1 expression vector and the effects of it on HLA-I expression in GES-1 cells in vitro].

AIM: To construct the human TAP1 expression vector and to evaluate its effects on HLA-I expression in GES-1 cells in vitro. METHODS: The human TAP1 expression vector (pcDNA3.1/V5-His-TAP1) was constructed by gene recombination technology. The expression of HLA-I on human gastric epithelial cell line (GES-1 cells) after transfection was detected by RT-PCR, Western blot and flow cytometry (FCM). RESULTS: Human full-length TAP1 gene was obtained from human peripheral blood mononuclear cells by RT-PCR reaction, then TAP1 gene was inserted into pcDNA3.1/V5-HisB vector to get the TAP1 expression vector (pcDNA3.1/V5-His-TAP1) by recombination technology including digestion with restriction enzymes, ligation and transformation. The vector was sequenced to ensure the sequence fidelity.To further evaluate the function of the TAP1 plasmid we constructed, GES-1 cells were selected as the target cell to be transfected. Firstly RT-PCR and Western blot results showed that the expression of TAP in GES-1 cells was increased after pcDNA3.1/V5-His-TAP1 transfection. Based on the high efficiency of transfection in GES-1 cell, we then detected the expression of HLA-I. The results showed that the expressions of HLA-A, HLA-B and HLA-C at mRNA level were all increased by TAP1 transfection, but no change was found in beta2m mRNA. HLA-I protein level was increased correspondingly with the TAP expression in cells by FCM and Western blot assay. CONCLUSION: The TAP1 expression vector was successfully constructed, and it can induce the expression of HLA-I on the GES-1 cells after TAP1 transfection. The results confirm that the TAP1 plays a cruical role in the HLA-I antigen expression and antigen presentation pathway.

Effect of RhoA signaling transduction on expression of Ezrin in breast cancer cell lines.

BACKGROUND AND OBJECTIVE: Both RhoA and Ezrin are confirmed to play an important role in the development and metastasis of tumors. However, the mechanism remains unclear. This study rudimentally investigates the regulatory effect of RhoA on the expression of Ezrin. METHODS: After MDA-MB-231 cells were treated with epidermal growth factor (EGF) or following pretreatment of fasudil (the special inhibitor of RhoA), the expression of RhoA, p-RhoA and Ezrin in MDA-MB-231 cells was detected by western blot. RESULTS: Stimulation of EGF triggered RhoA phosphorylation in MDA-MB-231 cells which reached the maximum at 30 min; RhoA expression did not change; Ezrin expression was enhanced and reached the maximum at 24 h. However, pretreatment of fasudil before EGF stimulation decreased RhoA phosphorylation and Ezrin expression in MDA-MB-231 cells by 72.73% and 51.28%, respectively. CONCLUSION: RhoA may regulate the invasion and metastasis of breast cancer cells as an upstream signaling of Ezrin.

[Relationship between expression of caveolin-1 and pERK1/2 and prognosis in non-small cell lung cancer].

OBJECTIVE: To study the relationship between expression of caveolin-1 (Cav-1) and pERK1/2 and prognosis in non-small cell lung cancer (NSCLC). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

[Relationship of ezrin protein expression to the carcinogenesis and prognosis of infitrating breast ductal carcinoma].

OBJECTIVE: To investigate the relationship of ezrin protein expression to the carcinogenesis and prognosis of infiltrating breast ductal carcinoma. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[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].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

[Correlation of serum pepsinogen level and gastric mucosal changes of residents in the high incidence area of gastric cancer].

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Studies on the cut-off value of serum pepsinogen abnormality for screening chronic atrophic gastritis and gastric carcinoma].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Expression and prognostic significance of survivin and caspase-3 in esophageal squamous-cell carcinoma and their relationship with HSPs expression].

OBJECTIVE: 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). METHODS: 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, 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. CONCLUSION: The expressions of survivin and caspase-3 are two independent prognostic factors in ESCC. They do not correlate with HSP27 and HSP70 expression.

[The inhibitory effect of deoxynivalenol on TAP-1 expression in human peripheral blood mononuclear cells in vitro].

AIM: To explore the effects of deoxynivalenol (DON) on transporter associated with antigen processing-1 (TAP-1) expression in human peripheral blood mononuclear cells (PBMCs). METHODS: Effects of various concentrations of DON on TAP-1 expression of in vitro cultured human PBMCs and the dose-effect relationship were analyzed by flow cytometry (FCM) and semi-quantitative RT-PCR at the protein and mRNA levels. RESULTS: FCM analysis indicated that treatment with various concentrations of DON could inhibit TAP-1 expressions in PBMCs, showing a negative correlation between DON concentration and TAP-1 expression. Semi-quantitative RT-PCR detection indicated that high concentrations of DON (1,000 and 2,000 microg/L) could distinctly inhibit TAP-1 mRNA expression. CONCLUSION: DON can down-regulate TAP-1 expression in human PBMCs in a dose-dependent manner in vitro, which suggests DON may interfere with host immunosurveillance, and this may account for the correlation between DON-contaminated grain and esophagus cancer in high risk area.

[Experimental lung carcinogenic in vivo study of aflatoxin G1 in NIH mice].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Oral administration of AFG1 can induce hyperplastic lesions and adenocarcinoma of lung in NIH mice.

[Carcinogenic effects of sterigmatocystin and deoxynivalenol in NIH mice].

OBJECTIVE: To further explore the carcinogenic activity of Sterigmatocystin (ST) and the possible synergistic carcinogenic effect of deoxynivalenol (DON) in NIH mice. METHODS: 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. RESULTS: 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. CONCLUSION: 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.