Cold exposure increases the risk of adverse events related to cardiovascular causes, especially in the elderly. In this review, we focus on recent findings concerning the impact of aging on the regulatory mechanisms of cold-induced cardiovascular responses. In response to cold exposure, the initial physiological thermoregulation in healthy young persons, such as cutaneous vasoconstriction to reduce heat loss, is attenuated in older individuals, resulting in a reduced ability of the older persons to maintain body temperature in cold environment. Impaired sympathetic skin response, reduced noradrenergic neurotransmitter synthesis, insufficient noradrenergic transmitters, and altered downstream signaling pathways inside the vascular smooth muscle may be among the underlying mechanisms for the maladaptive vasoconstrictive response to cold stress in the elderly. The increase in blood pressure during cold exposure in young persons may be further augmented in aging adults, due to greater central arterial stiffness or diminished baroreflex sensitivity with aging. Cold stress raises myocardial oxygen demand caused by increased afterload in both young and old adults. The elderly cannot adjust to meet the increased oxygen demand due to reduced left ventricular compliance and coronary blood flow with advancing age, rendering the elderly more susceptible to hypothermia-induced cardiovascular complications from cold-related diseases. These age-associated thermoregulatory impairments may further worsen patients' health risk with existing cardiovascular diseases such as hypertension, coronary artery disease, and heart failure. We searched PubMed for papers related to cold stress and its relationship with aging, and selected the most relevant publications for discussion.

The purposes of the present study were to elucidate the risk and prognostic effect of second primary cancers (SPCs) development, as well as the factors influencing the prognosis of OC patients with SPCs. A statistically significant increase in SPCs risk was observed among OC patients during 2004-2015. The independent factors were used to construct the SPCs-prediction nomogram and the OS-prediction nomogram. Both nomogram were subjected to internal validation and performed well. OC patients with SPCs have a better prognosis than patients without SPCs. Propensity score matching (PSM) was applied to reduce confounding.

BACKGROUND Cancer patients were found at a high risk of death from cardiovascular disease. This study aims to assess cardiovascular mortality risk and identify the potential risk factors associated with cardiovascular mortality among gastric cancer patients. METHODS Gastric cancer patients were collected from the Surveillance Epidemiology and End Results database during 1975-2016. Standardized mortality ratios were calculated to compare cardiovascular mortality rates between gastric cancer patients and the general US population. Univariable Cox analysis and multivariable stepwise Cox analysis were adopted to identify the potential risk factors for cardiovascular disease death after gastric cancer diagnosis. RESULTS There were 10 886 cardiovascular disease deaths identified among 165 433 individuals with gastric cancer observed for 410207.20 person-years. Gastric cancer patients were at a higher cardiovascular disease mortality risk (standardized mortality ratio = 3.35, 95% confidence interval: 3.24-3.47, P < 0.05). The study showed that older age at diagnosis (>80 years vs. 0-69 years, hazard ratio = 7.05, 95% confidence interval: 6.66-7.46, P < 0.001; 70-80 years vs. 0-69 years, hazard ratio = 3.35, 95% confidence interval: 3.19-3.53, P < 0.001), male sex (vs. female, hazard ratio = 1.39, 95% confidence interval: 1.33-1.45, P < 0.001), black race (vs. white, hazard ratio = 1.31, 95% confidence interval: 1.24-1.38, P < 0.001), without a partner (divorced/separated vs. married/partnered, hazard ratio = 1.35, 95% confidence interval: 1.25-1.45, P < 0.001; single vs. married/partnered, hazard ratio = 1.20, 95% confidence interval: 1.12-1.29, P < 0.001; widowed vs. married/partnered, hazard ratio = 1.41, 95% confidence interval: 1.34-1.48, P < 0.001), living in the northern plains (vs. pacific coast, hazard ratio = 1.23, 95% confidence interval: 1.16-1.29, P < 0.001) and surgery not performed (vs. performed, hazard ratio = 1.70, 95% confidence interval: 1.61-1.79, P < 0.001) were significantly associated with increased risk of cardiovascular disease death. Compared with patients with localized stage, distant staged patients were less likely to die of cardiovascular disease (hazard ratio = 0.88, 95% confidence interval: 0.83-0.94, P < 0.001). CONCLUSIONS Gastric cancer patients were at an increased risk of cardiovascular disease death. Older age at diagnosis, male sex, black race, without a partner, living in the northern plains and surgery not performed were significantly associated with cardiovascular disease death after gastric cancer diagnosis.

As one of the isoprenoids and widely derived from many fruits and vegetables, β-ionone (BI) has a potent inhibitory proliferation of cancer cells in vitro and in vivo. However, its exact mechanism is still uncompleted understood and needs to be further verified. Cyclooxygenase-2 (COX-2), as a potential target of cancer chemoprevention, has been played pivotal roles in proliferation of tumor cells and carcinogenesis. Thus, the objective of present study was to determine that BI inhibited the activity of COX-2 in breast cancer and related to cancer cell models. Cell proliferation, DNA synthesis, the distribution of cell cycle, apoptosis induction and the expression of P38-MAPK protein were determined in MCF-7 cells by methylene blue, 3H-thymidine (TdR) incorporation, flow cytometry, TUNEL and Western blotting assays. Quinone reductase (QR) activity was determined in murine hepatoma Hepa1c1c7 cells by enzyme-linked immunosorbent assay (ELISA). The expression of COX-2 in a phorbol-12-myristate-13-acetate (PMA)-induced cell model and mammary tumor tissues was examined by Western blotting and immunohistochemistry. The results showed that BI significantly inhibited cell proliferation and DNA synthesis, arrested the distribution of cell cycle at the S phase or decreased proteins related to cell cycle such as cyclin D1 and CDK4, induced apoptosis and increased the expression of p-P38 in MCF-7 cells. BI at low doses (< 50 μmol/L) significantly increased QR activity, decreased the expression of COX-2 protein and prostaglandin E2 (PEG2) release in cell models. In addition, BI also significantly decreased the expression of COX-2 protein in rat mammary tumor tissues. Therefore, our findings indicate that BI possesses inhibitory proliferation of breast cancer cells through down-regulation of COX-2 activity.

Ovarian cancer is the main cause of cancer mortality in gynecological tumors around the world. Drug resistance to a variety of chemotherapeutics continue to be one of the main causes of treatment failure. In a previous study, it was demonstrated that STK17A, a proapoptotic gene, was significantly downregulated in acquired resistance phenotypes of colon cancer cells that are resistant to oxaliplatin and 5-fluorouracil. Therefore in the present study, the association between STK17A expression and ovarian cancer with initial drug resistance was investigated and the influence of STK17 on ovarian cancer cell proliferation and doubling time. In the present study, ovarian cancer cell lines that express low levels of STK17A were established by targeting STK17A with specific siRNA. In addition, up-regulation of STK17A was established in ovarian cells by pCDNA3flu/STK17A. The sensitivity of the transfected cells and controls to paclitaxel, carboplatin was examined by MTT assay, and the levels of proliferation and apoptosis were analyzed by flow cytometry. In the cells that were transfected with siRNA resulting in reduced expression of STK17A, the 50% inhibitory concentration (IC50) of the chemotherapy drugs paclitaxel and carboplatin was increased compared with control cells (P<0.05). By contrast, in the cells that overexpressed STK17A following treatment with pCDNA3flu/STK17A, the IC50 of the chemotherapy drugs reduced in each case, and was significantly lower compared with the control (P<0.05). There was a variable susceptibility to carboplatin and paclitaxel resulting from altering the levels of STK17A expression in ovarian cancer cell lines. The growth of STK17A/siRNA transfected cells was promoted compared with that of the control cells and accordingly their cell doubling time was shortened.

γ-Tocotrienol, a major component of the tocotrienol-rich fraction of palm oil, has been suggested to have antioxidant and anticancer activity as well as potent chemopreventive effects on tumor cells. In this study, the mechanisms underlying γ-tocotrienol-mediated growth inhibition of human carcinoma HT-29 cells were further investigated, especially in correlation with the involvement of β-catenin/T-cell factor (Tcf) signaling pathway. We found that γ-tocotrienol could strongly suppress the transcriptional activity of β-catenin/Tcf signaling pathway in HT-29 cells. γ-Tocotrienol inhibited the expression level of total β-catenin protein but did not significantly affect the phosphorylated β-catenin level. Meanwhile, γ-tocotrienol down-regulated the protein level of nuclear β-catenin and induced its redistribution to cell membrane. Furthermore, γ-tocotrienol suppressed the expression of downstream target genes such as c-myc, cyclin D1 and survivin. The results demonstrated that γ-tocotrienol-inhibited growth and -induced apoptosis in HT-29 cells were accompanied by significant inhibition of β-catenin/Tcf signaling. Blocking the expression of β-catenin with small interfering RNA significantly suppressed the ability of γ-tocotrienol to reduce viability and induce apoptosis in HT-29 cells. Thus, our data suggested that γ-tocotrienol exerts its anticancer activity through β-catenin/Tcf signaling, and β-catenin is a target for γ-tocotrienol in the Wnt/β-catenin signaling pathway.

Antiangiogenic therapy mediated by food components is an established strategy for cancer chemoprevention. Growth factors play critical roles in tumor angiogenesis. A conditioned medium containing growth factors from human gastric adenocarcinoma SGC-7901 cell conditioned medium was used as an angiogenic stimulus in this study. The purpose of this study was to evaluate the inhibitory effect and possible mechanism of γ-tocotrienol on tumor angiogenesis. The results showed that γ-tocotrienol (10-40 μmol/L) significantly suppressed proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) induced by SGC-7901 cell conditioned medium in a dose-dependent manner. γ-Tocotrienol (800-1200 μg/egg) also inhibited new blood vessel formation on the growing chick embryo chorioallantoic membrane in a dose-dependent manner. Moreover, the inhibitory effects of γ-tocotrienol on HUVECs were correlated with inducing the apoptosis and arresting cell cycle at the G(0)/G(1) phase at a dose of 40 μmol/L γ-tocotrienol. In addition, γ-tocotrienol inhibited angiogenesis in HUVECs by down-regulation of β-catenin, cyclin D1, CD44, phospho-VEGFR-2 and MMP-9. The antiangiogenic effects of γ-tocotrienol on HUVECs may be attributable to regulation of Wnt signaling by decreasing β-catenin expression. Thus, our results suggest that γ-tocotrienol has a potential chemopreventive agent via antiangiogenesis.

The β-catenin gene is a critical component of Wnt signaling pathway. Aberrant activation of Wnt/β-catenin signaling and subsequent upregulation of β-catenin is related to enhancing cell proliferation and developing colon polyps and colon cancer. In the present study, the effect of β-catenin knockdown on the growth and survival of the human colon cancer cell line HT-29 was investigated in vitro. The effect of knockdown of β-catenin on cell proliferation was investigated by MTT assay and colony formation. The cell cycle distribution was investigated by flow cytometry. Apoptosis was measured by nuclear staining and flow cytometry. The change of β-catenin and related proteins were determined by western blotting and immunofluorescence. The results showed that small interfering RNA directed against β-catenin markedly inhibited the expression and nuclear translocation of β-catenin and decreased the expression of known target genes such as cyclin D1 and c-myc; HT-29 cell proliferation was inhibited as indicated by growth reduction, cell cycle arrest in G0/G1 phase, and induction of apoptosis; and the inhibition of cell growth may be associated with switching off cyclin D1 and c-myc expression by small interfering RNA targeted against β-catenin in colon cancer HT-29 cells.

Natural vitamin E is a mixture of two classes of compounds, tocopherols and tocotrienols. Recent research has revealed that tocotrienols, especially γ-tocotrienol, exhibit not only the same antioxidant ability as tocopherols, but also remarkable anticancer capacity in cancer cell lines. In this study, the invasion and metastatic capacities of gastric adenocarcinoma SGC-7901 cells and the correlation with antimetastasis mechanisms induced by γ-tocotrienol were explored. The results showed the inhibitory effects of γ-tocotrienol at doses of 15, 30, 45 and 60 μmol/L for 48 h on cell migration and cell matrigel invasion; activities of matrix metalloproteinase (MMPs) increased in SGC-7901 cells when compared to the control group (P<.05 or P<.01). An increasing trend in the chemotactic responses to fibronectin (FN) in SGC-7901 cells was found in the γ-tocotrienol treatments. SGC-7901 cell attachment decreased in the γ-tocotrienol-treated groups in comparison with the control group (P<.01). The mRNA expressions of MMP-2 and MMP-9 showed that γ-tocotrienol significantly reduced the matrigel invasion capability through down-regulation of the mRNA expressions of MMP-2 and MMP-9 (P<.01), and up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in SGC-7901 cells by treatment with γ-tocotrienol for 48 h (P<.05). γ-Tocotrienol also significantly increased the mRNA expression of nm23-H1 in SGC-7901 cells (P<.01). These findings suggest a potential mechanism of γ-tocotrienol-mediated antitumor metastasis activity and indicate the role of vitamin E as potential chemopreventative agents against gastric cancer.

Hypoxia is a common characteristic feature of solid tumors, and carcinoma cells are known to secrete many growth factors. These growth factors, such as vascular endothelial growth factor (VEGF), play a major role in the regulation of tumor angiogenesis and metastasis. In this study, the effect of γ-tocotrienol, a natural product commonly found in palm oil and rice bran, on the accumulation of HIF-1α protein and the paracrine secretion of VEGF in human gastric adenocarcinoma SGC-7901 cell line induced by cobalt(II) chloride (as a hypoxia mimic) was investigated. These results showed that cobalt(II) chloride induced the high expression of VEGF in SGC-7901 cells at dose of 150μmol/L for 24h. Both basal level and cobalt(II) chloride-induced HIF-1α protein accumulation and VEGF paracrine secretion were inhibited in SGC-7901 cells treated with γ-tocotrienol at 60μmol/L treatment for 24h. U0126, a MEK1/2 inhibitor, decreased the expression of HIF-1α protein and the paracrine secretion of VEGF under normoxic and hypoxic conditions. In this study, γ-tocotrienol also significantly inhibited the hypoxia-stimulated expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2). The mechanism seems to involve in inhibiting hypoxia-mediated activation of p-ERK1/2, it leads to a marked decrease in hypoxia-induced HIF-1α protein accumulation and VEGF secretion. These data suggest that HIF-1α/VEGF could be a promising target for γ-tocotrienol in an effective method of chemoprevention and chemotherapy in human gastric cancer.

Tocotrienols are naturally occurring isoprenoid compounds highly enriched in palm oil, rice bran, oat, wheat germ, barley and rye. Tocotrienols have antioxidant properties as well as potent anticancer properties. In this study, the mechanisms underlying the apoptosis of gamma-tocotrienol on human gastric adenocarcinoma SGC-7901 cells were further studied, especially in correlation with the involvement of the apoptotic pathway. gamma-Tocotrienol inhibited SGC-7901 cell growth in a concentration- and time-dependent manner. The inhibitory effects of SGC-7901 cells were correlated with the DNA damage and arresting cell cycle at G(0)/G(1) phase in a time-dependent manner at 60 mumol/L concentration of gamma-tocotrienol. gamma-Tocotrienol induced activation of caspase-3 and increased the cleavage of the downstream substrate poly(ADP-ribose) polymerase. Furthermore, gamma-tocotrienol-induced apoptosis on SGC-7901 cells was mediated by activation of caspase-9. The data in this study suggested that gamma-tocotrienol could induce the apoptosis on human gastric cancer SGC-7901 cells via mitochondria-dependent apoptosis pathway. Thus, our findings revealed gamma-tocotrienol as a potential, new chemopreventive agent for human gastric cancer.

Objective To investigate the relationship of the lymphangiogenesis and lymphatic metastasis by observing the expression of proliferating cell nuclear antigen in the hamster tongue cancer development and analyzing the correlations of lymph vessel density (LVD), lymphatic vessel area (LVA) and malignance or lymphatic metastasis of tongue cancer cells. Methods Forty_two hamster tongue cancer models were induced by painting 1.5% 7,12-dimethylben(a) anthracene (DMBA) acetone solution after scratching, 7 models were sacrificed every two weeks. The pathological changes of tongue cancer were determined by the HE staining. The lymphatic hyperplasia was determined by PCNA and Desmoplakin(DP I +Ⅱ) Immunohistochemical double staining. The tumors and lymphatic endothelial cell proliferation index (proliferation index, PI), lymphatic vessel density (LVD) and lymphatic vessel area (LVA) were measured and statistically analyzed. Results The oncogenesis of tongue was divided into three stages: atypical hyperplasia, carcinoma in situ and early invasive stage;atypical hyperplasia group:PI (91.55), LVA (7570.23), LVD (2.50);carcinoma in situ group: PI (113.36), LVA (12105.45), LVD (3.73);early invasive group: PI (124.67), LVA (14524.33), LVD (5.33). The PI, LVA and LVD were compared among groups above (P<0.05), and the correlation of PI with LVA and LVD was positive (P<0.05);Lymphatic metastasis group:PI (130.50), LVA (15430.67), LVD (6.17), non lymphatic metastasis group:PI (113), LVA (12711.67), LVD (3.67), the PI, LVA and LVD were compared between the two groups above (P<0.05).Conclusion With the development of hamster tongue cancer, lymphatic endothelial cell proliferation activity increased, suggesting that the lymphangiogenesis existed in the tongue carcinogenesis process;the values of the LVD and LVA increased in the hamster tongue cancer development, which was positively correlated with the cancer cell malignance and lymphatic metastasis.

Objective: To investigate the relationship between the S100P and the sensitivity of ovarian cancer to chemotherapeutics.Method: We established stable cell lines of ovarian cancer cells, SKOV3 and OVCAR3, that overexpress human S100P. We also transiently transfected the parent cell lines with S100P-targeted siRNA for down-regulation of S100P expression. The sensitivity of all transfected and untransfected cell lines to carboplatin and paclitaxel was detected by MTT assay.Results: For both cells, IC50s decreased to carboplatin and paclitaxel (p < 0.05), with overexpression of S100P compared to untransfected cells. Alternatively, with down-regulation of S100P by siRNA, the IC50 to carboplatin and paclitaxel increased in each case (p < 0.05), which was significantly higher compared to untransfected cells.Conclusion: Changes in expression levels of S100P in SKOV3 and OVCAR3 cells results in variable susceptibility to carboplatin and paclitaxel. These data suggest that S100P contributes to chemosensitivity to carboplatin and paclitaxel in ovarian cancer cells. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

S100P is a member of the S100 family of calcium-binding proteins. Our previous studies have demonstrated its significant downregulation in oxaliplatin-resistant colon cancer cell line. The present study investigated whether it plays a role in the regulation of chemosensitivity to anticancer drugs using human ovarian cancer cell line OVCAR3. We firstly overexpressed S100P in the OVCAR3 cell line, and evaluated the expression level of S100P by semiquantitative RT-PCR, Western blotting and immunofluorescence assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay indicated that overexpression of S100P sensitized OVCAR3 cells for chemotherapeutic drugs (paclitaxel, oxaliplatin, 5-fluorouracil, etoposide and epirubicin) induced cytotoxicity more than vector-only controls. Further studies showed that downregulation of S100P by RNA interference in OVCAR3 cells led to a significant increase of resistance to each of these anticancer drugs. Taken together, our results suggest that S100P plays an important role in regulation of chemosensitivity to anticancer drugs in ovarian cancer cells. Using S100P as a molecular biomarker may increase our ability to predict tumor drug response in ovarian cancer.

Recent studies indicate that S100P expression may be a biomarker that can predict the success of cancer chemotherapy. Whether it is relevant to chemotherapeutics in ovarian cancer is unknown. In this study, we investigated the association of S100P expression with paclitaxel sensitivity in ovarian cancer cell lines.We measured S100P expression and paclitaxel resistance profiles in parent SKOV3 and OVCAR3 cell lines. Then, the two cell lines were transiently transfected with S100P siRNA. We also constructed an OVCAR3 cell clone that stably overexpressed S100P. The effect of S100P expression level on the survival of cells exposed to paclitaxel was measured using the MTT assay. S100P expression was evaluated by semi-quantitative RT-PCR and Western blotting. Significance of differences was calculated using independent samples t-test and one way analysis of variance (ANOVA).Lower S100P expression was associated with a survival advantage in OVCAR3 cells exposed to paclitaxel; the survival advantage in SKOV3 cells was smaller (P < 0.05). The survival advantage associated with decreased S100P expression was even greater for SKOV3 and OVCAR3 cells that had been transfected with S100P siRNA before being exposed to paclitaxel (P < 0.05). Consistent with this, the OVCAR3 cell clone that was transfected to overexpress S100P was more sensitive to paclitaxel (P < 0.05).Low S100P expression contributes to drug resistance to paclitaxel in ovarian cancer cell lines. S100P expression thus might be a marker that can predict the effectiveness of paclitaxel based chemotherapy. Such a marker could be helpful in improving individual medication regimens for ovarian cancer patients.

Tocotrienols have been shown to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in tocotrienol-induced apoptosis are still unclear. In the present study, gamma-tocotrienol induced apoptosis in human gastric adenocarcinoma SGC-7901 cell line through down regulation of the extracellular signal-regulated kinase (ERK) signalling pathway. Furthermore, gamma-tocotrienol-induced apoptosis was accompanied by down regulation of Bcl-2, up regulation of Bax, activation of caspase-3, and subsequent poly (ADP-ribose) polymerase cleavage. These results indicated that up or down regulation of Bcl-2 family proteins play a major role in the initiation of gamma-tocotrienol-induced apoptosis as an activator of caspase-3. Gamma-tocotrienol also down regulated the activation of the Raf-ERK signalling pathway, and down regulated c-Myc by decreasing the expressions of Raf-1 and p-ERK1/2 proteins. The results suggest that key regulators in tocotrienol-induced apoptosis may be Bcl-2 families and caspase-3 in SGC-7901 cells through down regulation of the Raf-ERK signalling pathway.

Objective To investigate the effects of Weipi granules on gastric mucosa epithelial cell apoptosis and expressions of Bcl-2,P53 and Fas in patients with precancerous gastric mucosal lesions,and to study the mechanism of Weipi granules for treatment of this condition.Methods Forty-six patients were randomized to receive Weipi-I granules and Weifuchun-I tablets(treatment group,n=30),Weipi-II granules and Weifuchun-II tablets(control group,n=16)for 6 consecutive months,then subjected to designated tests.Results After medication,the treatment group showed increased and higher apoptosis index as compared with the controls.Significant differences were also indicated in expressions of Bcl-2,P53 and Fas between the two groups.Conclusion Weipi granules showed a regression of precancerous gastric mucosal lesions.The suppressed Bcl-2 and mutant P53 expressions,enhanced Fas expression and an increase in apoptosis index,all these factors constitute a therapeutic benefit for normal programmed cell death in heterotypically proliferative gastric mucosa,may contribute to the efficacy of Weipi granules in these patients.

AIM:To investigate the effect of c9,t11-conjugated linoleic acid (c9,t11-CLA) on the adhesion of human gastric carcinoma cell line (SGC-7901).METHODS:SGC-7901 cells were at first treated with different concentrations (25, 50, 100, 200 micromol/L) of c9,t11-CLA and 1 mL/L ethanol (as a negative control) for 24 h. Using adhesion assay and Western blot, we investigated the ability of SGC-7901 cells to adhere to intracellular matrix and examined the expression of E-cadherin (ECD), alpha-catenin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in these cells.RESULTS:The attachment rate to laminin of SGC-7901 cells treated with different concentrations of c9,t11-CLA (0, 25, 50, 100, and 200 micromol/L) was 100.0+/-3.3, 95.7+/-4.0, 89.2+/-4.6, 87.9+/-6.1, and 65.9+/-5.8, respectively. The attachment rate to fibronectin was 100.0+/-4.7, 96.8+/-3.8, 94.5+/-4.1, 76.5+/-4.3, and 61.8+/-4.8, respectively. The attachment rate to Matrigel was 99.9+/-6.6, 91.4+/-6.8, 85.5+/-7.4, 79.3+/-5.6, and 69.6+/-5.1, respectively. Besides, c9,t11-CLA could increase the level of ECD and alpha-catenin, and decrease the level of ICAM-1 and VCAM-1 in SGC-7901 cells.CONCLUSION:c9,t11-CLA can reduce the adhesion of human gastric carcinoma cells to laminin, fibronectin and Matrigel. c9,t11-CLA can increase the level of ECD and alpha-catenin, and decrease the level of ICAM-1 and VCAM-1 in human gastric carcinoma cells.

Objective To investigate common chromosomal changes and the LOH frequency of microsatellite loci in primary gastric cancer samples in order to locate the deleted regions in which human gastric cancer related genes might exist.Methods Comparative genomic hybridization (CGH) was used to define global chromosomal aberrations in 43 primary gastric tumors. Based on the results of CGH, analysis of loss of heterozygosity (LOH) was performed in chromosome 19 in which the loss was first discovered in the gastric cancers. The PCR-based approach was used to investigate 22 loci, which are spaced at 1.1-10.9 cM intervals throughout chromosome 19. The amplified PCR fragments were subjected to electrophoresis in PAGE gel and analyzed with GenescanTM and GenotyperTM. Results CGH analysis revealed gains in chromosome 3p(8/43), 8q(8/43), 20 [20 (9/43), 20p(7/43), 20q(4/43)], 12q(16/43), 13q(12/43) and losses in 19 [19 (15/43)], 7 [17 (8/43), 17p (10/43)], 16 (10/43) and 1p (11/43). Among the 43 evaluated samples, the most frequent LOH was detected at locus D19S571 (27.81%). Conclusions The tumorigenesis of gastric cancer includes several chromosomal changes. The aberration of chromosome 19 was the first common change founded in gastric cancer. The region near the D19S571 might harbor potential genes related to the tumorigenesis of gastric cancer.

Comparative genomic hybridization (CGH) has been applied to detect recurrent chromosome alterations in 62 primary gastric carcinomas. Several nonrandom chromosomal changes, including gains of 8q (31 cases, 50%), 20q (29 cases, 47%) with a minimum gain region at 20q11.2–q12, 13q (21 cases, 34%) with a minimum gain region at 13q22, and 3q (19 cases, 31%) were commonly observed. The regions most frequently lost included: 19p (23 cases, 37%), 17p (21 cases, 33%), and 1p (14 cases, 23%). High copy number gain (DNA sequence amplification) was detected in 6 cases. Amplification of 8q23–q24.2 and 20q11.2–q12 were observed in 3 cases. Gain of 20q and loss of 19p were confirmed by fluorescence in situ hybridization using corresponding bacterial artificial chromosomes (BAC) clones from those regions. The gain and loss of chromosomal regions identified in this study provide candidate regions involved in gastric tumorigenesis.