Endoscopic classification and pathological features of primary intestinal lymphangiectasia.

BACKGROUND: The appearance of the intestinal mucosa during endoscopy varies among patients with primary intestinal lymphangiectasia (PIL). AIM: To classify the endoscopic features of the intestinal mucosa in PIL under endoscopy, combine the patients' imaging and pathological characteristics of the patients, and explain their causes. METHODS: We retrospectively analyzed the endoscopic images of 123 patients with PIL who were treated at the hospital between January 1, 2007 and December 31, 2018. We compared and analyzed all endoscopic images, classified them into four types according to the endoscopic features of the intestinal mucosa, and analyzed the post-lymphographic computed tomography (PLCT) and pathological characteristics of each type. RESULTS: According to the endoscopic features of PIL in 123 patients observed during endoscopy, they were classified into four types: nodular-type, granular-type, vesicular-type, and edematous-type. PLCT showed diffuse thickening of the small intestinal wall, and no contrast agent was seen in the small intestinal wall and mesentery in the patients with nodular and granular types. Contrast agent was scattered in the small intestinal wall and mesentery in the patients with vesicular and edematous types. Analysis of the small intestinal mucosal pathology revealed that nodular-type and granular-type lymphangiectasia involved the small intestine mucosa in four layers, whereas ectasia of the vesicular- and edematous-type lymphatic vessels largely involved the lamina propria mucosae, submucosae, and muscular layers. CONCLUSION: Endoscopic classification, combined with the patients' clinical manifestations and pathological examination results, is significant and very useful to clinicians when scoping patients with suspected PIL.

The m6A/m5C/m1A Regulated Gene Signature Predicts the Prognosis and Correlates With the Immune Status of Hepatocellular Carcinoma.

RNA modification of m6A/m5C/m1A contributes to the occurrence and development of cancer. Consequently, this study aimed to investigate the functions of m6A/m5C/m1A regulated genes in the prognosis and immune microenvironment of hepatocellular carcinoma (HCC). The expression levels of 45 m6A/m5C/m1A regulated genes in HCC tissues were determined. The functional mechanisms and protein-protein interaction network of m6A/m5C/m1A regulated genes were investigated. The Cancer Genome Atlas (TCGA) HCC gene set was categorized based on 45 m6A/m5C/m1A regulated genes, and survival analysis was used to determine the relationship between the overall survival of HCC patients in subgroups. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct the risk model and nomogram for m6A/m5C/m1A regulated genes. The relationships between m6A/m5C/m1A regulated gene subsets and risk model and immune cell infiltration were analyzed using CIBERSORT. m6A/m5C/m1A regulated genes were involved in mRNA and RNA modifications, mRNA and RNA methylation, mRNA and RNA stability, and other processes. There was a statistically significant difference between cluster1 and cluster2 groups of genes regulated by m6A/m5C/m1A. The prognosis of cluster1 patients was significantly better than that of cluster2 patients. There were statistically significant differences between the two cluster groups in terms of fustat status, grade, clinical stage, and T stage of HCC patients. The risk model comprised the overexpression of YBX1, ZC3H13, YTHDF1, TRMT10C, YTHDF2, RRP8, TRMT6, LRPPRC, and IGF2BP3, which contributed to the poor prognosis of HCC patients. The high-risk score was associated with prognosis, fustat status, grade, clinical stage, T stage, and M stage and was an independent risk factor for poor prognosis in HCC patients. High-risk score mechanisms included spliceosome, RNA degradation, and DNA replication, among others, and high-risk was closely related to stromal score, CD4 memory resting T cells, M0 macrophages, M1 macrophages, resting mast cells, CD4 memory activated T cells, and follicular helper T cells. In conclusion, the cluster subgroup and risk model of m6A/m5C/m1A regulated genes were associated with the poor prognosis and immune microenvironment in HCC and are expected to be the new tools for assessing the prognosis of HCC patients.

Metallothionein 1M (MT1M) inhibits lung adenocarcinoma cell viability, migration, and expression of cell mobility-related proteins through MDM2/p53/MT1M signaling.

BACKGROUND: Metallothionein 1M (MT1M) functions to regulate cell proliferation and cancer metastasis. This study assessed the effects of MT1M overexpression and mouse double minute 2 homolog (MDM2) knockdown on the regulation of non-small cell lung cancer A549 cell viability, migration, and protein expression in vitro and explored the underlying molecular events. METHODS: A549 cells were stably infected with lentivirus carrying MT1M cDNA or transiently transfected MDM2 siRNA and/or treated with the p53 inhibitor for the assessment of changes in cell viability, wound healing, Transwell migration, and qRT-PCR and Western blot assays. Luciferase reporter assay was performed to investigate p53 binding to the MT1M promoter. RESULTS: The data showed that MT1M overexpression inhibited A549 cell viability and migration capacity in vitro, whereas the p53 inhibitor reversed the inhibition of A549 cell viability and migration caused by MT1M overexpression as well as the expression of MMP2, MMP9, and MMP14. Furthermore, knockdown of MDM2, an upstream inhibitor of p53 activity, was able to reduce A549 cell viability, migration, and protein expression. Thus, MDM2 knockdown had synergistic effects with MT1M overexpression on the suppression of A549 cell viability, migration, and protein expression. CONCLUSIONS: In conclusion, MDM2 can bind to and phosphorylate p53 protein to inactivate the protein, thereby reducing MT1M expression and leading to tumor cell proliferation and migration.

[Effect of SRC Kinase on Adriamycin Resistance and Invasion and Metastasis in Human Breast Cancer Cells].

OBJECTIVE: To investigate the role of SRC kinase inhibitor PP2 in drug resistance to adriamycin (ADM) in breast cancer cells and invasion, metastasis of cells. METHODS: MTT assay was used to detect the inhibitory effect of ADM on MCF-7 and MCF-7/ADM cells. The 50% inhibitory concentration (IC50) and resistance index (RI) of cells were calculated. The expression of MDR1, connexin 43 (Cx43) and SRC proteins in breast cancer cells were detected by Western blot assay. Transwell experiment and cell scratch test were used to determine the invasion and migration of cells respectively [MCF-7, MCF-7/ADM, PP2 (1, 2, 4 µmol/L)]. Standard colony formation assay was used to detect the cytotoxicity effect of 4 µmol/L PP2 pretreatment on ADM. RESULTS: ADM inhibited the proliferation of MCF-7 more than MCF-7/ADM cells (P<0.01). The IC50 of MCF-7/ADM cells was 24.55 µmol/L, the IC50 of MCF-7/ADM cells was 770.57 µmol/L, the RI was 31. Compared with MCF-7 cells, expressions of the multidrug resistance proteins MDR1 and SRC were significantly increased (P<0.01). The invasion and migration ability of the MCF-7/ADM cells was stronger than that of the sensitive cells (P<0.01). When MCF-7/ADM was exposed to SRC inhibitor PP2, the invasion and metastasis ability of cells were inhibited (P<0.01) and the rate of colony formation was decreased, that is, more sensitivity to ADM (P<0.01). CONCLUSION: The resistance of MCF-7 to ADM is accompanied by increased expression of SRC. SRC inhibitor PP2 can reduce the cell resistance, ability of invasion and metastasis.

Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice.

AIMS: The receptor tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile. In this study, we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. RESULTS: Here, we show that the endothelial cell-specific deletion of ErbB4 induces decreased exploratory behavior in adult mice. However, the water maze task for spatial memory and the memory reconsolidation test reveal no changes; additionally, we observe no impairment in CaMKII phosphorylation in Cdh5Cre;ErbB4f/f mice, which indicates that the endothelial ErbB4 deficit leads to decreased exploratory activity rather than direct memory deficits. Furthermore, decreased brain metabolism, which was measured using micro-positron emission tomography, is observed in the Cdh5Cre;ErbB4f/f mice. Consistently, the immunoblot data demonstrate the downregulation of brain Glut1, phospho-ULK1 (Ser555), and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively, our findings suggest that endothelial ErbB4 plays a critical role in regulating brain function, at least in part, through maintaining normal brain energy homeostasis. CONCLUSIONS: Targeting ErbB4 or the modulation of endothelial ErbB4 signaling may represent a rational pharmacological approach to treat neurological disorders.

Diazoxide accelerates wound healing by improving EPC function.

Endothelial cell dysfunction is the primary cause of microvascular complications in diabetes. Diazoxide enables beta cells to rest by reversibly suppressing glucose-induced insulin secretion by opening ATP-sensitive K+ channels in the beta cells. This study investigated the role of diazoxide in wound healing in mice with streptozotocin (STZ)-induced diabetes and explored the possible mechanisms of its effect. Compared to the controls, mice with STZ-induced diabetes exhibited significantly impaired wound healing. Diazoxide treatment (30 mg/kg/d, intragastrically) for 28 days accelerated wound closure and stimulated angiogenesis in the diabetic mice. Circulating endothelial progenitor cells (EPCs) increased significantly in the diazoxide-treated diabetic mice. The adhesion, migration, and tube formation abilities of bone marrow (BM)-EPCs were impaired by diabetes, and these impairments were improved by diazoxide treatment. The expression of both p53 and TSP-1 increased in diabetic mice compared to that in the controls, and these increases were inhibited significantly by diazoxide treatment. In vitro, diazoxide treatment improved the impaired BM-EPC function and diminished the increased expression of p53 and TSP-1 in cultured BM-EPCs caused by high glucose levels. We conclude that diazoxide improved BM-EPC function in mice with STZ-induced diabetes, possibly via a p53- and TSP-1-dependent pathway.

[Sodium valproate enhances doxorubicin cytotoxicity in breast cancer cells in vitro].

OBJECTIVE: To investigate the effect of sodium valproate, a histone deacetylase inhibitor, on the cytotoxicity of doxorubicin in breast cancer cells. METHODS: Western blotting was used to assess Cx43 protein expression in breast cancer Hs578T cells exposed to doxorubicin and sodium valproate. MTT assay was used to determine the cytotoxicity of doxorubicin; annexin V/PI double staining and Hochest 33258 fluorescence staining were employed to detect doxorubicin-induced early and late apoptosis, respectively. RESULTS: Western blotting showed that sodium valproate significantly increased Cx43 protein expression in Hs578T cells (P/0.01). The cells exposed to both sodium valproate and doxorubicin showed significantly lowered cell viability compared with the cells exposed to doxorubicin alone (P/0.01). Exposure to both sodium valproate and doxorubicin resulted in significantly increased early and late cell apoptosis rate compared with doxorubicin treatment alone (P/0.01). CONCLUSION: sodium valproate can significantly enhance the cytotoxicity of doxorubicin and increase doxorubicin-induced apoptosis in breast cancer cells in vitro possibly by enhancing the gap junction function.

Glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice.

BACKGROUND: Sepsis is a common disease that continues to increase in incidence in the world. Diseases, such as diabetes mellitus, may make the situation worse. Diabetic patients are at increased risk for common infections. This study was designed to investigate the role of glibenclamide on myocardial injury by lipopolysaccharides (LPS) in streptozotocin induced diabetic mice (STZ-mice). METHODS: LPS was used to induce endotoxemia in STZ-mice. Heart rate and mean arterial pressure were measured by MPA-HBBS. Serum epinephrine level was measured by enzyme-linked immunosorbent assays (ELISA). Myocardial injury was examined by light and transmission electron microscope and TUNEL staining. Macrophage infiltration was measured by immunohistochemistry. Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels in myocardial tissue and serum in STZ-mice, and in conditional medium of primary cultured peritoneal macrophages were determined by ELISA. Nalp3 and Caspase-1 protein levels were measured by Western blotting analysis. RESULTS: STZ administration decreased body weight and increased blood glucose in C57BL/6 mice. LPS injection caused decreases of heart rate and mean arterial pressure, and elevated serum epinephrine level in C57BL/6 mice. Compared with control mice without STZ treatment, LPS induced more severe myocardial injury and macrophage infiltration in STZ-mice, which was attenuated by pretreatment of glibenclamide. LPS stimulation enhanced the levels of IL-1ß and TNF-α in both cardiac tissue and serum. Glibenclamide pretreatment significantly inhibited the serum levels of pro-inflammatory cytokines. Either high glucose or LPS increased the levels of IL-1ß and TNF-α in the conditional medium of peritoneal macrophages. Glibenclamide treatment suppressed the increase of IL-1ß level induced by high glucose and LPS. Furthermore, Nalp3 and Caspase-1 levels were markedly increased by high glucose plus LPS, and both proteins were significantly inhibited by glibenclamide treatment. CONCLUSIONS: We conclude that glibenclamide could attenuate myocardial injury induced by LPS challenge in STZ-mice, which was possibly related to inhibiting inflammation through Nalp3 inflammasomes.

Activation of alpha 7 nicotinic acetylcholine receptor protects mice from radiation-induced intestinal injury and mortality.

Radiation-induced gastrointestinal syndrome occurs when the body is exposed to a high dose of radiation. Currently, safe and effective radioprotectants are not available. Apoptosis was reported to play a primary role in radiation-induced injury. Recent evidence suggests that stimulation of α7 nicotinic acetylcholine receptor (α7nAChR) prevents cell death by inhibition of apoptosis. In this study, we demonstrated that a single dose of PNU282987 (100 µg/kg, i.p.), a selective α7nAChR agonist, protected mice from intestinal injury and significantly improved survival when administered prior to lethal 8 Gy total body irradiation. In vitro, PNU282987 protected against 8 Gy radiation-induced cell death in human umbilical venous endothelial cells by inhibiting apoptosis. We conclude that activation of α7nAChR may provide a new therapeutic pathway for the treatment of radiation-induced damage and mortality.

Total flavonoids of litsea coreana enhance the cytotoxicity of oxaliplatin by increasing gap junction intercellular communication.

Oxaliplatin is widely used in the treatment of variety of cancers, including cancer of the testis and colorectum. Gap junctions (GJs) can amplify the cytotoxicity of antinoeoplastic drugs through the bystander effect in different cancer cells. In this study, we demonstrate that total flavonoids of litsea coreana (TFLC), one extract from the dried leaves of litsea coreana leve, increase the cytotoxicity of oxaliplatin in mouse testicular cancer I-10 cells. We found that cell survival was substantially decreased only when functional GJs formed in I-10 cells. TFLC increased oxaliplatin cytotoxity (inducing cell death and apoptosis) by enhancing gap junction intercellular communication (GJIC) through elevated Cx43 protein expression. Furthermore, apoptosis-related protein (Bax, Bcl-2, caspase-3/9) results showed that the Bax/Bcl-2 ratio and activated caspase-3/9 increased when TFLC was used compared with treatment with oxaliplatin alone, which suggests that the mechanism of increased oxaliplatin-induced apoptosis was through the mitochondrial pathway. These results demonstrate that TFLC can enhance the cytotoxicity of oxaliplatin, and that these processes may be regulated in testicular tumor cells through GJ-mediated regulation of tumor cell apoptosis.

[PP2 enhances intercellular communication of gap junction in breast cancer Hs578T cells].

OBJECTIVE: To investigate the effect of Src kinase inhibitor PP2 on intercellular communication of gap junction in breast cancer cells. METHODS: Cultured breast cancer Hs578T cells were treated with various concentrations of pp2 (0,1,2,4,8,16,32 µmol/L) for 24h. Cell growth was determined by MTT assay; dye spread in Hs578T cells was measured by Parachute assay; and the expression of Src kinase in Hs578T cells was detected by Western blot. RESULTS: MTT assay showed that the survive rate of Hs578T cells treated with PP2 (1 ≊ 8 µmol/L) was 98% ± 3% ≊ 94 % ± 4%. Parachute assay showed that compared to control group the standard normalized dye spread rates of Hs578T cells treated with 1,2,4 and 8 µmol/L PP2 were 1.60 ± 0.08,2.00 ± 0.05,2.20 ± 0.05 and 2.70 ± 0.09,respectively (all P<0.01). Moreover,compared to control group at the same time points,the standard normalized dye spread of Hs578T cells treated with 8 µmol/L PP2 for 6,12 and 24 h were 1.4 ± 0.05,1.7 ± 0.06,and 2.2 ± 0.07,respectively (all P<0.01). Western blot showed that the expression ratios of Src kinase/ß-actin of Hs578T cells treated with 1,2,4 and 8 µmol/L PP2 for 24 h were 0.93 ± 0.02,0.70 ± 0.09,0.66 ± 0.09 and 0.36 ± 0.10,which were significantly inhibited compared with control group (P<0.05 or 0.01). And the expression ratio of Src kinase/ß-actin of Hs578T cells treated with 8 µmol/L PP2 for 6,12 and 24h was 0.82 ± 0.03,0.66 ± 0.08 and 0.59 ±0.09, which were all inhibited significantly compared to control group (P<0.01). CONCLUSION: PP2 enhances the gap junction function in breast cancer Hs578T cells, which is probably related to the inhibition of Src kinase.

Role of Kir6.2 subunits of ATP-sensitive potassium channels in endotoxemia-induced cardiac dysfunction.

BACKGROUND: Cardiac dysfunction is well-described in endotoxemia and diagnosed in up to 60% of patients with endotoxic shock. ATP-sensitive potassium (KATP) channels are critical to cardiac function. This study investigates the role of Kir6.2 subunits of KATP channels on cardiac dysfunction in lipopolysaccharide (LPS)-induced endotoxemia. METHODS: Kir6.2 subunits knockout (Kir6.2-/-) and wild-type (WT) mice were injected with LPS to induce endotoxemia. Cardiac function was monitored by echocardiography. Left ventricles were taken for microscopy (both light and electron) and TUNEL examination. Serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities, and tumor necrosis factor-α (TNF-α) levels in both serum and left ventricular tissues were determined. RESULTS: Compared to WT, Kir6.2-/- mice showed significantly declined cardiac function 360 min after LPS administration, aggravated myocardial damage and elevated serum LDH and CK activities. Apoptotic cells were obviously increased in heart tissues from Kir6.2-/- mice at 90, 180 and 360 min. TNF-α expression in both serum and heart tissues of Kir6.2-/- mice was significantly increased. CONCLUSIONS: We conclude that Kir6.2 subunits are critical in resistance to endotoxemia-induced cardiac dysfunction through reducing myocardial damage by inhibition of apoptosis and inflammation. KATP channels blockers are extensively used in the treatment of diabetes, their potential role should therefore be considered in the clinic when patients treated with antidiabetic sulfonylureas are complicated by endotoxemia.

[Influence of Cx26/Cx32 gap junction channel on antineoplastic effect of etoposide in Hela cells].

OBJECTIVE: To observe the influence of Cx26/Cx32 gap junction channel on the antineoplastic effect of etoposide in Hela cervical cancer cells. METHODS: Fluorescence trace was used to assay the gap junction intercellular communication mediated by Cx26/Cx32 in Hela cells and its functional modulation by the pharmacological agents (oleamide, retinoid acid). A standard colony-forming assay was applied to determine the cell growth-inhibiting effect of etoposide in Hela cells with functional modulation of the gap junction. Hoechst 33258 staining was used to assess the changes in etoposide-induced apoptosis of Hela cells with altered gap junction functions. RESULTS: Oleamide markedly decreased while retinoid acid obviously increased the gap junction function in Hela cells. Standard colony-forming assay showed that etoposide produced a lowered antiproliferative effect in Hela cells with reduced gap junction and an increased antiproliferative effect in cells with enhanced gap junction function. In cells with a reduced gap junction function, etoposide induced a lowered apoptosis rate, which increased obviously in cells with an enhanced gap junction function. CONCLUSION: The antineoplastic effect of etoposide is reduced in Hela cells with a decreased gap junction intercellular communication mediated by Cx26/Cx32 and is enhanced in cells with an increased gap junction intercellular communication.

PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma.

BACKGROUND: Prenylated Rab acceptor 1 domain family member 3 (PRAF3) is involved in the regulation of many cellular processes including apoptosis, migration and invasion. This study was conducted to investigate the effect of PRAF3 on apoptosis, migration and invasion in human esophageal squamous cell carcinoma (ESCC). METHODS: The expression of PRAF3 mRNA and protein in primary ESCC and the matched normal tissues (57cases) was determined by quantitative RT-PCR and Western blot. Immunohistochemical analysis of PRAF3 expression was carried out in paraffin-embedded sections of ESCC and correlated with clinical features. The role of PRAF3 in apoptosis, migration and invasion was studied in ESCC cell lines of Eca109 and TE-1 through the adenovirus mediated PRAF3 gene transfer. The effect of PRAF3 on apoptosis was analyzed by annexin V-FITC assay. The regulation of PRAF3 on migration was determined by transwell and wounding healing assay, while the cellular invasion was analyzed by matrigel-coated transwell assay. RESULTS: We found that the expression of PRAF3 was significantly down-regulated in ESCC tissue compared with the matched normal tissue and was correlated with the clinical features of pathological grade, tumor stage and lymph node metastasis. Moreover, overexpression of PRAF3 induced cell apoptosis through both caspase-8 and caspase-9 dependent pathways, and inhibited cell migration and invasion by suppressing the activity of both MMP-2 and MMP-9 in human ESCC cell lines. CONCLUSIONS: Our data suggest that PRAF3 plays an important role in the regulation of tumor progression and metastasis and serves as a tumor suppressor in human ESCC. We propose that PRAF3 might be used as a potential therapeutic agent for human ESCC.

Systemic perfluorohexane attenuates lung injury induced by lipopolysaccharide in rats: the role of heme oxygenase-1.

Clinical trials with partial liquid ventilation demonstrate improvement in oxygenation, as well as some adverse side effects linked to the application of liquid perfluorocarbons (PFCs) during liquid ventilation. Thus, we examined the effects of systemic administration of PFC on acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its effects on heme oxygenase-1 (HO-1), a compound that provides potent cytoprotection against lung injury. Rats were assigned to one of six groups (n = 8). Thirty minutes after they were challenged with LPS aerosol inhalation, perfluorohexane was given intraperitoneally every two hours. Ten hours after LPS inhalation, bronchoalveolar lavage fluid (BALF) and lung tissue were obtained for enzyme linked immunosorbent assay, histologic, and Western-blot analyses. The results showed that perfluorohexane significantly decreased the wet to dry weight ratio, malondialdehyde (MDA) production, and myeloperoxidase (MPO) activity in the lung tissue. Also, perfluorohexane reduced the total protein content and levels of tumor necrosis factor-alpha (TNF-alpha) but increased the levels of the anti-inflammatory cytokine interleukin-10 (IL-10) in the BALF, resulting in decreased pulmonary edema and the infiltration of neutrophils into the lung tissues of LPS-treated rats. Furthermore, perfluorohexane increased HO-1 protein production and stimulated HO-1 activity in the lung tissue. Pre-treatment with Zinc protoporphyrin IX, an inhibitor of HO-1, decreased the protective effects of perfluorohexane in rats. In summary, systemic perfluorohexane alleviates LPS-induced lung injury in rats, and HO-1 may be involved in the mechanism of this reduction.

[Correlations of polymorphisms of TGFB1 and TGFBR2 genes to genetic susceptibility to gastric cancer].

BACKGROUND & OBJECTIVE: Transforming growth factor beta (TGFbeta) signaling pathway plays an important role in the genesis and progression of tumors through regulating cell proliferation and differentiation. The concentration of TGFbeta1 in plasma and the expression of TGFbeta receptor II (TGFbetaRII) are correlated to the development of certain tumors, including gastric cancer. This study was to explore the correlations of functional genetic variants in TGFB1 and TGFBR2 genes to the genetic susceptibility to gastric cancer. METHODS: A case-control study was conducted in Yixing City, a high incidence area of gastric cancer. Polymorphisms of TGFB1 C-509T, TGFB1 Leu10Pro, and TGFBR2 G-875A in 256 gastric cancer patients and 303 cancer-free controls, frequency-matched by age and sex, were determined by primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR). Crude and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were measured by multivariate Logistic regression analysis to evaluate the correlations of the polymorphisms to the susceptibility to gastric cancer. RESULTS: The TGFB1 C-509T and TGFB1 Leu10Pro were in high linkage disequilibrium (D'=0.86). Compared with wild-type homogenous genetypes -509CC and 10 Leu/Leu, variant genetypes -509CT/TT, 10 Leu/Pro, and 10 Pro/Pro decreased the risk of gastric cancer by 49% and 34% (adjusted OR=0.51, 95% CI=0.36-0.74 for -509CT/TT; adjusted OR=0.66, 95% CI=0.45-0.98 for 10 Leu/Pro or 10 Pro/Pro). The risk of gastric cancer was decreased along with the number of variant sites in the TGFB1 C-509T and TGFBR2 G-875A (Chi(2)=15.70,P < 0.001). Stratified analysis showed that the protective effects of the genotypes were obvious in the subjects of no more than 60-year old (OR=0.42, 95% CI=0.23-0.79) and in non-drinkers (OR=0.45, 95% CI=0.27-0.74). CONCLUSION: Genetic variants of TGFB1 and TGFBR2 genes may contribute to the risk of developing gastric cancer in an eastern Chinese population in Yixing city.