Dietary vitamin D intake and vitamin D related genetic polymorphisms are not associated with gastric cancer in a hospital-based case-control study in Korea

There have been few studies on the association between vitamin D levels and gastric cancer in Asian populations, but no studies have been performed on the interactions between vitamin D intake and polymorphisms in the vitamin D pathway. The effects of vitamin D intake, vitamin D related genetic polymorphisms, and their association with the incidence of gastric cancer were investigated in a hospital case-control study, including 715 pairs of newly diagnosed gastric cancer patients and controls matched for age and sex. Correlations between vitamin D intake and plasma vitamin D concentrations were also assessed in a subset of subjects. No statistically significant difference was observed in the dietary intake of vitamin D between the patients and controls, nor were there any evident associations between vitamin D intake and risk of gastric cancer in multivariate analyses. Vitamin D intake significantly correlated with the circulating 25-hydroxyvitamin D levels, but not with the active form of the vitamin, 1,25-dihydroxyvitamin D. There were no statistically significant interactions between vitamin D intake, and VDR or TXNIP polymorphisms. This study suggests that dietary vitamin D intake is not associated with gastric cancer risk, and the genetic polymorphisms of vitamin D-related genes do not modulate the effect of vitamin D with respect to gastric carcinogenesis.     

Clinicopathological correlation and prognostic significance of sonic hedgehog protein overexpression in human gastric cancer

Objectives: This study investigated the expression of Sonic Hedgehog (Shh) protein in gastric cancer, and correlated it with clinicopathological parameters. The prognostic significance of Shh protein was analyzed. Methods: Shh protein expression was evaluated in 113 cases of gastric cancer and 60 cases of normal gastric mucosa. The immunoreactivity was scored semi quantitatively as: 0 = absent; 1 = weak; 2 = moderate; and 3 = strong. All cases were further classified into two groups, namely non-overexpression group with score 0 or 1, and overexpression group with score 2 or 3. The overexpression of Shh protein was correlated with clinicopathological parameters. Survival analysis was then performed to determine the Shh protein prognostic significance in gastric cancer. Results: In immunohistochemistry study, nineteen (31.7%) normal gastric mucosa revealed Shh protein overexpression, while eighty-one (71.7%) gastric cancer revealed overexpression. The expression of Shh protein were significantly higher in gastric cancer tissues than in normal gastric mucosa (P < 0.001), which was statistically correlated with age (P = 0.006), tumor differentiation (P < 0.001), depth of invasion (P = 0.042), pathologic staging (P = 0.017), and nodal metastasis (P = 0.019). We found no significant difference in both overall and disease free survival rates between Shh overexpression and non-expression groups P = 0.168 and 0.071). However, Shh overexpression emerged as a significant independent prognostic factor in multivariate Cox regression analysis (hazard ratio 1.187, P = 0.041). Conclusions: Shh protein expression is upregulated and is statistically correlated with age, tumor differentiation, depth of invasion, pathologic staging, and nodal metastasis. The Shh protein overexpression is a significant independent prognostic factor in multivariate Cox regression analysis in gastric cancer.     

Correlation of RKIP,STAT3 and cyclin D1 expression in pathogenesis of gastric cancer

RKIP is proposed as a new metastasis suppressor. Our recent study showed that RKIP inhibits malignant phenotypes of gastric cancer cells. However, the underlying mechanism of RKIP function in gastric cancer is unclear. This study aimed to investigate the correlation of RKIP, STAT3 and cyclin D1 expression in the tumorigenesis of gastric cancer. RKIP, STAT3 and cyclin D1 proteins were detected by immunohistochemistry in tissues of gastric ulcer (n = 27), gastric adenomatous polyp (n = 7), intestinal metaplasia (n = 26), dysplasia (n = 40), gastric carcinoma (n = 169) and metastatic lymph node (n = 36). RKIP, STAT3 and cyclin D1 mRNA levels were analyzed by RT-PCR in SGC7901 cells. We found that RKIP protein expression was significantly decreased in advanced gastric cancer and metastatic lymph node tissues while cyclin D1 and STAT3 protein expression was markedly increased in severe dysplasia, gastric cancer and metastatic lymph node tissue (P < 0.01). RKIP expression in gastric cancer was negatively correlated with the invasion, TNM stage and lymphoid node metastasis (P < 0.01), while cyclin D1 and STAT3 expression was positively correlated with histological differentiation and lymphoid node metastasis (P < 0.01). RKIP protein level was negatively correlated with cyclin D1 and STAT3 protein level, while cyclin D1 protein level was positively correlated with STAT3 protein level in gastric cancer samples. Moreover, reconstitution of RKIP in SGC7901 gastric cancer cells led to reduced cyclin D1 and STAT3 mRNA levels. In conclusion, these data suggest that RKIP inhibits gastric cancer metastasis via the downregulation of its downstream target genes STAT3 and cyclin D1.     

Expression of Tim-3 in gastric cancer tissue and its relationship with prognosis

As a negative regulatory molecule, T-cell immunoglobulin–and mucin domain-3 (Tim-3) plays a crucial role in the tumor immunological tolerance. In the present study, we aimed to determine the Tim-3 expression in gastric cancer tissue and its relationship with clinicopathological parameters and prognosis. The Tim-3 expression was assessed in 52 gastric cancer specimens and 15 gastritis tissues by flow cytometry, and gastritis tissues served as the control. As a result, we found that the Tim-3 expressions on CD4⁺T cells and CD8⁺T cells in gastric cancer tissue was significantly higher than those in gastritis tissue (P=0.022, P=0.047, respectively). The median expression level of Tim-3 on CD4⁺T cells were significantly correlated with clinicopathological parameters, such as tumor size, lymph node metastasis, the depth of tumor invasion and TNM staging (P=0.042, P=0.026, P=0.001, P=0.003, respectively), while it was not correlated with sex, age and histological subtype (all P>0.05). In CD8⁺T cells, the Tim-3 expression was relevant to tumor invasion and TNM staging (P=0.035, P=0.017, respectively), while it was irrelevant to other clinicopathological parameters (all P>0.05). Additionally, Kaplan-Meier survival curves showed that the median overall survival time of patients with lower Tim-3 expression was greater than that of patients with higher Tim-3 expression in CD4⁺T cells and CD8⁺T cells (χ²=18.036, P<0.001 and χ²=18.036, P<0.001, respectively). Moreover, the multivariate analysis revealed that the Tim-3 expression and TNM stage were independent prognostic factors for gastric cancer patients (P=0.029, P=0.043 and P=0.003, respectively). These results suggest that Tim-3 played an important role in the development and progression of gastric cancer, and it could be used as an independent prognostic factor for gastric cancer patients.     

CEACAM5 has different expression patterns in gastric non-neoplastic and neoplastic lesions and cytoplasmic staining is a marker for evaluation of tumor progression in gastric adenocarcinoma

Objective

The aim of this study was to investigate the expression patterns of CEACAM5 in non-neoplastic and neoplastic gastric lesions, as well as its application in the differential diagnosis and its relationship with tumor progression.

Methods

CEACAM5 expression was detected by immunohistochemical staining in the serial sections of the gastric neoplastic and non-neoplastic lesions. The impacts of CEACAM5 expression patterns on tumor progression were evaluated by statistics, the clinical and pathological data included sex, age, tumor extension, lymph node involvement and tumor staging.

Results

There was no CEACAM5 expression in normal gastric epithelial cells. In hyperplastic polyps, CEACAM5 was expressed with apical membranous staining in the hyperplastic and prolonged gastric pit adjacent to the surface. Intestinal metaplasia (IM) expressed CEACAM5 mainly with membranous pattern, and some cases showed membranous staining mixed with cytoplasmic staining. GIN expressed CEACAM5 mainly with membranous staining, but the mixed staining of cytoplasmic and membranous patterns increased, and especially in the high grade GIN, cytoplasmic staining of CEACAM5 began to occur. Compared with IM and GIN, CEACAM5 expression patterns of hyperplastic polyp showed a significant difference (P = 0.000). IM, low grade GIN and the whole GIN showed no significant difference in CEACAM5 expression patterns (P = 0.355), but IM and high grade GIN showed a significant difference (P = 0.027). There was a significant difference between low and high grade GIN (P = 0.002). GIN and well-differentiated carcinomas showed no significant difference (P = 0.070), but low grade GIN and well differentiated carcinomas showed a significant difference (P = 0.006). In gastric adenocarcinomas, CEACAM5 expression patterns showed a significant difference in tumor grading (P = 0.010) and Laurén classification (P = 0.001). In histological grading, well differentiated carcinomas showed more membranous staining than moderately and poorly differentiated, and more cytoplasmic CEACAM5 staining was detected in moderately and poorly differentiated carcinomas. Similar to that, in Laurén classification, intestinal carcinomas showed more membranous staining, and diffuse carcinomas showed more cytoplasmic staining. Moreover, CEACAM5 expression patterns showed a significant difference in tumor extension (P = 0.012), lymph node involvement (P = 0.015) and tumor staging (P = 0.002), suggesting that CEACAM5 should be involved in tumor progression. In advanced carcinomas, CEACAM5 was expressed with more cytoplasmic staining regardless of the histological classification.

Conclusion

CEACAM5 had different expression patterns in gastric non-neoplastic and neoplastic lesions. The CEACAM5 expression patterns were associated with tumor progression. Membranous staining of CEACAM5 might be a marker of premalignancy in gastric lesions, and cytoplasmic CEACAM5 might enhance tumor invasion and migration and be an evaluated marker for progressive and advanced gastric cancer. Also, it might be useful for the differential diagnosis of gastric premalignant lesions.     

胃癌中HSDL2过表达与临床病理特征的相关性

目的探讨羟基类固醇脱氢酶样蛋白2(hydroxysteroid dehydrogenase like 2,HSDL2)在胃癌中的表达及与临床病理特征的关系。方法采用免疫组化SP两步法检测HSDL2蛋白在90例胃癌和20例正常胃组织中的表达,分析HSDL2蛋白过表达与胃癌临床病理特征的关系,并采用GEPIA数据库进行生存分析。结果HSDL2蛋白主要定位于胃癌细胞SGC-7901和AGS的细胞质中。UALCAN数据库分析结果显示:胃癌组织中HSDL2 mRNA的表达水平明显高于正常胃组织(P<0.05)。HSDL2蛋白在胃癌组织中过表达,强阳性率为58.9%(53/90),显著高于正常胃组织(5.0%,1/20)(P<0.01)。HSDL2蛋白表达与胃癌分化程度、临床分期及肿瘤直径密切相关(P均<0.05),与患者性别、年龄及淋巴结转移无明显相关性。GEPIA数据库分析结果显示,HSDL2蛋白过表达胃癌患者无瘤生存率低于HSDL2蛋白低表达患者(P<0.05)。结论HSDL2在胃癌组织中明显过表达,其表达水平与胃癌的发生、发展及不良预后密切相关,有望成为胃癌患者预后评估的重要指标。     

Increased chemokine receptor IL-17RA expression is associated with poor survival in gastric cancer patients

Background: Previous researchers have identified that the chemokine interleukin-17 (IL-17) was associated with survival time of patients with gastric cancer, but the roles of its receptors (IL-17R) in gastric cancer remain unknown. Our studies were designed to clarify the function of IL-17RA and to explore their potential role in gastric cancer. Materials and methods: The expression of IL-17RA was determined in primary gastric cancer tissues (n=101) using Real-time RT-PCR, immunohistochemistry, and western blotting. To investigate the functional significance of IL-17RA expression, IL-17RA expression and clinical parameters, multivariate survival was analyzed in patients with gastric cancer. Results: IL-17RA was overexpression in gastric cancer tissues compared with adjacent normal tissues (P<0.05). The elevated expression level of IL-17RA was observed correlated significantly with tumor progression (P=0.003), Lymphatic invasion (P=0.019), lymphoid nodal status (P=0.001), distant metastasis (P<0.001) of gastric cancer patients, TNM stage (P=0.0013) and was one of the independent prognostic factors for patient’s overall survival. Conclusions: These results demonstrated that the expression of IL-17RA plays an important role in gastric cancer progression, migration and prognosis of gastric cancer. The IL-17-IL-17RA signaling mechanism may be a potential novel target.     

The role of vitamin D receptor gene polymorphisms in the susceptibility to prostate cancer of a southern European population

 Epidemiological data indicate a relationship between ultraviolet radiation, vitamin D, and prostate cancer risk. Antiproliferative effects of vitamin D require the expression of the nuclear vitamin D receptor (VDR). A three-fold increase in prostate cancer risk associated with the less active vitamin D receptor allele (the T allele from VDR TaqI polymorphism at codon 352) was reported. The role of VDR genotypes in the susceptibility to prostate cancer has not yet been studied in populations of southern Europe. In the present study, we determined VDR TaqI genotypes in Portuguese prostate cancer cases (n= 163) and controls (n= 211), a southern European population. When cases were compared with controls, we found an association of VDR T allele with prostate cancer risk (odds ratio [OR] = 1.87, 95% confidence interval [CI] 1.02–3.37; P= 0.035). This association was confirmed using logistic regression analysis (OR = 2.11, 95% CI 1.15–3.88; P= 0.015) and in particular associated to risk of prostate cancer onset in men over the age of 66 years (OR = 2.36, 95% CI 1.05–5.29; P= 0.036). Fifty percent of cases older than 66 years could be attributed to the influence of this risk factor. Our results indicate that the contribution of VDR genotypes to prostate cancer susceptibility might depend on the population studied and its geographic localization, and that VDR genotypes are important in the definition of the genetic risk profile of populations of southern Europe. Received: March 13, 2002 / Accepted: March 25, 2002     

MRP-1/CD9基因在胃癌及其癌前病变中的差异表达

目的　筛选和鉴定与胃癌发生、发展相关的基因片段 ,探讨胃癌的癌变分子机理。方法　应用荧光 m RNA差异显示技术对胃正常黏膜、癌前病变及癌组织的基因差异表达情况进行了分析。对其中的运动相关蛋白 (motility- related protein- 1,MRP- 1/CD9)基因 ,用 Northern印迹及逆转录 -聚合酶链反应技术分析在正常及不同病理状态下该基因表达的情况。结果　Northern印迹结果与 m RNA差异显示的结果相符合 ,逆转录 -聚合酶链反应显示 MRP- 1/CD9在胃癌组织中的表达 (0 .31± 0 .18)低于相应的正常胃黏膜 (0 .4 9± 0 .2 4 )及癌前病变组织 (0 .4 7± 0 .18) ,差异有显著性 (P<0 .0 5 ) ;在胃癌中 ,MRP- 1/CD9在弥漫型胃癌中的表达 (0 .2 2± 0 .17)明显低于肠型胃癌 (0 .38± 0 .16 ) (P<0 .0 5 )。结论　与正常胃黏膜及癌前病变组织相比 ,MRP- 1/CD9基因在胃癌组织中表达明显降低 ,提示 MRP- 1/CD9基因的表达情况可能与胃癌的发病及其组织学分型有关。     

High expression of integrin-linked kinase predicts aggressiveness and poor prognosis in patients with gastric cancer

Integrin-linked kinase (ILK), an intracellular serine/threonine protein kinase, has been reported to be highly expressed in many human malignancies, including gastric cancer. However, the prognostic significance of ILK expression in gastric cancer remains to be elucidated. In the present study, ILK expression in 95 gastric tumor tissues and 30 adjacent non-cancerous gastric mucosa was evaluated by immunohistochemistry and correlated with clinicopathological characteristics and patients’ outcome. The results showed that high ILK expression was observed in 47.4% (45/95) of gastric cancer tissues, but only in 20.0% (6/30) of adjacent gastric mucosa. Clinicopathological analysis indicated that high ILK expression was significantly associated with poor tumor differentiation (P = 0.024), advanced TNM stage (P = 0.006), tumor invasion (P = 0.001), and lymph node metastasis (P = 0.014). Kaplan–Meier survival curves demonstrated that patients with high ILK expression had substantially shorter overall survival that those with low ILK expression (P = 0.043, log-rank test). Furthermore, Cox multivariate regression analysis identified ILK expression as an independent prognostic factor for overall survival of gastric cancer patients (hazard ratio, 1.95; 95% confidence interval, 1.02–3.13; P = 0.026). In conclusion, our data suggest that ILK may contribute to the malignant progression of gastric cancer and serve as a novel prognostic indicator for gastric cancer patients.     

MicroRNA-153 expression and prognosis in non-small cell lung cancer

Background: miR-153 has been found to be significantly decreased in non-small cell lung cancer (NSCLC) tissues; however, its clinical significance has not been investigated. Methods: The expression patterns of miR-153 in 137 pairs of human lung cancer tissues and adjacent normal lung tissues were analyzed using qRT-PCR. The relationships between miR-153 expression and clinicopathological parameters were examined by chi-square test. Kaplan-Meier method and the log-rank test were used to determine the difference in overall survival (OS) rates between two groups. Results: The expression of miR-153 was reduced significantly, compared with adjacent normal lung tissues (P<0.05). We observed that the expression level of miR-153 was positively correlated with the clinical stage (P=0.005), lymph node status (P=0.014), distant metastasis (P=0.004), and differentiated degree (P<0.001) in NSCLC patients. According to the Kaplan-Meier survival analysis, the patients with low miR-153 expression exhibited evidently poorer overall survival rates than those with high miR-153 expression (P=0.003). Multivariate analysis showed that the expression of miR-153 was an independent and significant factor associated with poor OS rates (P=0.002). Conclusion: Decreased expression of miR-153 might be a potential unfavorable prognostic factor for patients with NSCLC, and further studies would be needed to prove our findings.     

NOTUM基因在胃癌组织中的表达及临床病理意义

目的:检测NOTUM基因在胃癌组织中的表达情况,探讨其与胃癌患者的临床病理关系.方法:收集2014年10月至2015年4月在中国人民解放军总医院普通外科手术治疗的胃癌标本及正常胃黏膜组织80例,采用免疫组织化学方法检测胃癌组织及胃黏膜正常组织中NOTUM基因的表达情况,分析NOTUM基因的表达与患者的临床病理及预后的关系.采用免疫印迹检测NOTUM蛋白及β-catenin蛋白的表达量,使用SPSS进行相关性分析确定NOTUM蛋白与β-catenin蛋白之间的关系.应用Kaplan-Meier方法比较NOTUM阳性表达胃癌患者与阴性表达胃癌患者在术后生存时间的差异.分别采用Log-rank检验和Cox回归模型对可能影响预后的临床病理特征进行单因素和多因素分析.结果:胃癌组织中NOTUM基因的表达显著增加,其表达与淋巴结转移及TNM分期及预后生存相关(P＜0.05),与患者的年龄、性别、肿瘤发生部位、肿瘤大小及肿瘤病理类型无关.胃癌组织中NOTUM基因和β-catenin蛋白的表达呈正相关.在NOTUM基因表达阳性的胃癌患者的生存时间明显缩短.NOTUM基因表达可以作为影响胃癌患者生存的独立危险因素.结论:胃癌中NOTUM基因在胃癌组织中呈高表达,可作为判断胃癌患者疾病进展及预后的生物学标志物.     

Defective control of vitamin D receptor‐mediated epithelial STAT1 signalling predisposes to severe respiratory syncytial virus bronchiolitis

Respiratory syncytial virus (RSV) infection causes bronchiolitis in infants with seasonal frequency, for which vitamin D deficiency and a well‐described polymorphism in the vitamin D receptor (VDR) FokI are important risk factors. Recent studies suggest that vitamin D regulates immune pathways in airway epithelial cells during RSV infection. It is not understood why the VDR FokI polymorphism predisposes to severe RSV bronchiolitis. We investigated how the VDR FokI polymorphism regulates the epithelial response to RSV infection. To this end, we over‐expressed the normal and FokI VDR variants in A549 airway epithelial cells. Vitamin D restrained the expression of both NFκB‐ and STAT1‐induced antiviral genes. However, while NFκB control by vitamin D remained intact, both RSV‐induced phosphorylation of STAT1 and expression of its downstream targets, IRF1 and IRF7, escaped vitamin D control in FokI epithelial cells. The poor capacity of vitamin D to regulate IRF1 in FokI VDR‐expressing cells was recapitulated using blood samples from normal and FokI VDR‐genotyped healthy donors. Hence, we provide mechanistic insight that the FokI VDR polymorphism renders STAT1‐mediated antiviral immune reactions to RSV infection non‐responsive to vitamin D control, resulting in enhanced immunopathology and exacerbated RSV bronchiolitis. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Downregulation of growth differentiation factor-15 in trichostatin A-induced apoptosis could play a role in progression of gastric cancer

Aim: To investigate the effect of trichostatin A (TSA) on gastric cancer cell line BGC-823, and identify the differentially expressed genes induced by TSA, which might participate in the progression of gastric cancer. Methods: MTT, fluorescence microscopy, and flow cytometry were used to detect the effect of TSA on growth inhibition and apoptosis of BGC-823 cells. Using gene microarray, we analyzed the changes in gene expression. Change in growth differentiation factor-15 (GDF-15) was verified by qRT-PCR and Western blotting. The expression of GDF-15 in gastric cancer and adjacent normal tissues was detected by immunohistochemistry. Results: Apoptosis of BGC-823 cells induced by TSA (75 ng/mL for 48 h) was demonstrated by flow cytometry. There were significant variations between TSA treated groups and control groups (P = 0.02). Nuclear chromatin condensation and fluorescence intensity were observed by fluorescence microscopy. GDF-15 gene expression and protein level were significantly reduced in the TSA treated group (75 ng/mL for 48 h). Immunohistochemistry demonstrated that the expression of GDF-15 in gastric adenocarcinoma was significantly higher than in the surrounding normal tissues (P < 0.05). Conclusion: Lower GDF-15 gene expression due to TSA-induced apoptosis was found in gastric cancer cell line BGC-823. Higher GDF-15 gene expression was seen in gastric adenocarcinoma tissues.     

Clinical significance of prostaglandin E synthase expression in gastric cancer tissue

Studies have linked microsomal prostaglandin E synthase (mPGES)-1 with gastric cancer. The purpose of this study was to determine mPGES-1, mPGES-2, and cytosolic PGES (cPGES) expression in gastric cancer and to evaluate the correlation between mPGES-1 and mPGES-2 expression and clinicopathological factors and cyclooxygenase-2 expression. PGES protein expression was examined by Western blot in gastric cancer cell lines and in biopsy samples from patients with gastric cancer. mPGES-1, mPGES-2, and cPGES protein localizations were examined immunohistochemically in 129 archival gastric cancer surgical resections. mPGES-1 protein expression was found in gastric cancer biopsies and cancer cell lines with differentiated or undifferentiated adenocarcinoma. There was no mPGES-1 expression in nonneoplastic biopsies. All cell lines and tissue samples expressed mPGES-2 and cPGES. Immunohistochemical analysis showed cancer cells expressed mPGES-1 in 47% of cases. mPGES-2 immunoreactivity was seen both in nonneoplastic glandular epithelium and cancer cells; however, cancer cell immunoreactivity was significantly more pronounced in 29% of cases. cPGES expression was constitutive both in nonneoplastic and neoplastic tissues, with no significant variation among cases. mPGES-1 and mPGES-2 expression correlated with cyclooxygenase-2 expression. mPGES-1 and mPGES-2 expression, and tumor-node-metastasis stage had independent prognostic significance under multivariate analysis in patients with gastric cancer overall and in patients with differentiated cancers. However, only tumor-node-metastasis stage and mPGES-2 expression retained independent prognostic significance in patients with poorly differentiated cancers. mPGES-1 and mPGES-2 correlate with clinicopathological factors and may be valuable prognostic factors in gastric cancer.     

Smad4/Smad7 balance: A role of tumorigenesis in gastric cancer

Smad signaling pathway plays an important role in tumorigenesis and progression in cancer (Halder, S.K., Rachakonda, G., Deane, N.G., Datta, P.K., 2008. Smad7 induces hepatic metastasis in colorectal cancer. Br. J. Cancer 99, 957-965). The protein level of Smad is associated with growth, inhibition, and metastasis in different cancers. It is unclear if the differentiation, metastasis and apoptosis are reduced by Smad expression pattern in gastric cancer. To determine the effect of Smad on gastric cancer cells, we investigated the relationship of Smad4/Smad7 expression, and differentiation, metastasis, and apoptosis in different gastric cancer. The results show that Smad4 expression in the gastric cancer tissue was dramatically lower than that in the peritumoral tissue. A lower expression of Samd4 was significantly lower in the poorly differentiated tissue than that in the well and middle differentiated tissues (P < 0.01). In contrast, Smad7 expression in gastric cancer tissues was significantly higher than that in the peritumoral tissue. Smad7 was overexpressed in poorly differentiated tissue, also higher than those in the middle, and well differentiated tissues (P < 0.05). The Smad4 or Smad7 expression obviously related with the lymphatic metastasis in gastric cancer. There were 45 cases with lymphatic metastasis in all 78 patients. Smad4 expression in the cases with lymphatic metastasis was lower than the cases without metastasis (P < 0.01), whereas Smad7 expression in the cases with lymphatic metastasis was much higher than the case without metastasis (P < 0.01). To better understand the mechanisms involved in tumorigenesis of gastric cancer, we established SGC7901 gastric cancer cell lines transduced with Smad4 or Smad7 plasmid DNA. Apoptosis and survival of cancer cells was induced after Smad4 and Smad7 transduction. This effect is concentration and time dependent. Thus, this study provides a mechanism by which a balance between Smad4 and Smad7 in human gastric cancer is critical for differentiation, metastasis, and apoptosis of tumor cells.     

Vitamin D receptor and CD86 expression in the skin of vitamin D-deficient swine

The immunomodulatory role of vitamin D in many diseases is well established. However, the relationship between vitamin D status and skin cancers is unclear. In this study, we examined the effect of vitamin D deficiency and sufficiency on VDR, NF-κB, and CD86 in the epidermis of Yucatan microswine tragi. All of these proteins have known roles in the pathogenesis of cutaneous malignancies such as melanoma and non-melanoma skin cancer. There was weaker and less discrete nuclear staining for VDR and weaker CD86 immunoreactivity with patchy membranous expression in the epidermis of vitamin D-deficient compared to vitamin D-sufficient swine. There was no difference in the immunostaining for NF-κB. Since VDR and CD86 expression are decreased in the setting of melanoma and non-melanoma skin cancers, our findings suggest a potential role of vitamin D-deficiency in the progression of skin malignancies.