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ABSTRACT: BACKGROUND: Increasing interest has been devoted to the expression and possible role of sex hormone receptors in gastric cancer, but most of these findings are controversial. In the present study, the expression profile of sex hormone receptors in gastric cancer and their clinicopathological and prognostic value were determined in a large Chinese cohort. METHODS: The mRNA and protein expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR), and androgen receptor (AR) in primary gastric tumors and corresponding adjacent normal tissues from 60 and 866 Chinese gastric cancer patients was detected by real-time quantitative PCR and immunohistochemistry method, respectively. The expression profile of the four receptors was compared and their associations with clinicopathological characteristics were assessed by using Chi-square test. The prognostic value of the four receptors in gastric cancer was evaluated by using univariate and multivariate Cox regression analysis. RESULTS: The presence of ERalpha, ERbeta, PR, and AR in both gastric tumors and normal tissues was confirmed but their expression levels were extremely low except for the predominance of ERbeta. The four receptors were expressed independently and showed a decreased expression pattern in gastric tumors compared to adjacent normal tissues. The positive expression of the four receptors all correlated with high tumor grade and intestinal type, and ERalpha and AR were also associated with early TNM stage and thereby a favorable outcome. However, ERalpha and AR were not independent prognostic factors for gastric cancer when multivariate survival analysis was performed. CONCLUSIONS: Our findings indicate that the sex hormone receptors may be partly involved in gastric carcinogenesis but their clinicopathological and prognostic significance in gastric cancer appears to be limited.
BMC Cancer 12/2012; 12(1):566. · 3.01 Impact Factor
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ABSTRACT: Silver chloride (AgCl) nanocrystals were formed and grown on silk fibroin fibers (SFFs) by a room-temperature process. Practically,
the degummed SFFs were immersed into silver nitrate solution and sodium chloride solution in turn. The amino acids on the
SFF surface were negatively charged in alkaline impregnant, providing locations to immobilize silver ions and form silver
chloride seeds. AgCl nanocrystals can further grow into cubic AgCl nanocrystals with an edge of about 100 nm. The morphologies
of the AgCl nanocrystals were mostly influenced by the concentration of sodium chloride solution and the special configurations
of the SFFs. The target AgCl/SFF nanocomposites constructed by AgCl nanocrystals and substrate SFFs could be used as photocatalysts
in water splitting and antibacterial agents. This work provides an important example in the introduction of natural biofibers
to the synthesis of functional hybrid nanocomposites by a green and mild technique.
Applied Physics A 04/2012; 102(2):429-434. · 1.63 Impact Factor
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Yongjie Zhang,
Xia Zhang,
Xi Wang,
Lu Gan,
Guanzhen Yu, Ying Chen,
Ke Liu,
Ping Li,
Jun Pan,
Jiejun Wang,
Shukui Qin
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ABSTRACT: Many tumors metabolise the majority of the glucose that they take up through glycolysis even in the presence of an adequate oxygen supply. Lactate dehydrogenase A (LDH-A) is the critical enzyme that catalyses the transformation of pyruvate to lactate. We demonstrate that LDH-A reduction can suppress the tumorigenicity of intestinal-type gastric cancer (ITGC) cells by downregulating Oct4 both in vitro and in vivo. A statistical analysis of 661 ITGC specimens showed a significant correlation between LDH-A and Oct4 expression. Moreover, patients with low LDH-A/negative Oct4 expression exhibited better overall survival than patients with other combinations. We conclude that the close correlation of LDH-A and Oct4 may offer a promising therapeutic strategy for ITGC.
Cancer letters 03/2012; 321(1):45-54. · 4.86 Impact Factor
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ABSTRACT: BACKGROUD: SPARC-like protein 1 (SPARCL1), a member of extracelluar matrix glycoprotein, is involved in many physiological functions.
Tissue microarray (TMA) blocks were constructed based on 1,072 Chinese patients, containing both gastric cancer (GC) tissues and adjacent normal mucosa tissues. We analyzed the expression of SPARCL1 from both mRNA and protein level, using Real-time quantitative polymerase chain reaction (qRT-PCR), semi-quantitative PCR, immunohistochemistry (IHC), and Western blotting. Loss of heterozygosity analysis at the SPARCL1 gene locus was carried out using ten paired tumor and matched normal tissues.
SPARCL1 mRNA was significantly reduced in tumor specimens compared with normal tissues. Down-regulation of SPARCL1 protein was detected in 413 cases (38.7%) of 1,072 primary gastric tumor tissues. Kaplan-Meier survival curves demonstrated that SPARCL1-positive patients had better median survival time than SPARCL1-negative patients (59 months vs. 28 months, P = 0.001). Multivariate survival analysis revealed that SPARCL1 was an independent prognostic factor in gastric adenocarcinoma patients with no metastasis and well/moderately differentiated. The incidence of LOH for each individual marker was 12.5% (1/8) for D4S2462, 20% (2/10) for D4S2929, and 33.3% (3/9) for SPARCL1.
Our study revealed the clinical significance of SPARCL1 expression, providing a basis that the loss of SPARCL1 is a negative event in GC progression and prognosis. Furthermore, SPARCL1 protein might be considered to be a potential differentiation marker.
Journal of Surgical Oncology 01/2012; 105(1):31-7. · 2.10 Impact Factor
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ABSTRACT: System A amino acid transporter is a Na+-dependent active transport system, mediating the uptake of amino acids, dysregulation of which has been found to be associated with malignant transformation in mammalian cells. However, the role of ATA1 in hilar cholangiocarcinoma is unclear. Here, we investigated ATA1 expression and determined its clinical significance in hilar cholangiocarcinoma. Tissue microarray blocks containing tumor specimens obtained from 48 patients were constructed. Expression of ATA1 in these specimens was analyzed using immunohistochemical studies. ATA1 overexpression was observed in 22 cases (44.9%). Overexpression of ATA1 was significantly associated with lymph node metastases. ATA1 expression has a significant correlation with recurrence and poor survival in univariate analyses. Multivariate analyses revealed that ATA1 was an independent predictor for future recurrence in patients with cholangiocarcinoma. Increased expression of ATA1 is frequent in human hilar cholangiocarcinoma and significantly correlated with the progression of cholangiocarcinoma, suggesting the importance of ATA1 in cancer development and progression. ATA1 expression may be used to predict recurrence and death and can serve as a promising target for therapy of this malignancy.
Journal of Surgical Research 12/2011; 171(2):663-8. · 2.25 Impact Factor
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ABSTRACT: EphB2 is a member of the Eph receptor tyrosine kinase family that has been involved in the regulation of cytoskeleton organization and cell migration in various cell types. Its role and regulation in carcinogenesis is controversial, especially in gastric cancer. We detected EphB2 expression and determined its clinical significance and explored its underlying molecular mechanism in gastric cancers.
Tissue microarray blocks containing primary gastric cancer, lymph node metastases, and adjacent normal mucosa specimens obtained from 337 Chinese patients were constructed. Expression of EphB2 in these specimens was analyzed using immunohistochemistry. Mutation analysis at the A9 tract in exon 17 and loss of heterozygosity analysis at the EphB2 gene locus were carried out in 13 sporadic EphB2-negative gastric cancers.
Complete loss of EphB2 expression was observed in 177 (52.5%) of the 337 primary tumor and 41 (82%) of the 50 nodal metastases. Loss of EphB2 expression was significantly associated with advanced T stage, nodal metastasis, advanced disease stage, and poor histological differentiation. Loss of EphB2 expression correlated significantly with poor survival rates in both univariate and multivariate analysis. No frameshift mutation, but a higher frequency of allelic loss, was found in EphB2-negative primary and metastatic tumor samples.
Frequent deletion and decreased expression of EphB2 protein suggested it as a negative biomarker for gastric carcinogenesis and a potential predictor of the outcome of patients with gastric cancer.
Journal of Cancer Research and Clinical Oncology 03/2010; 137(1):73-80. · 2.56 Impact Factor
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ABSTRACT: The putative tumor metastasis suppressor 1(MTSS1) is an actin-binding scaffold protein that has been implicated to play an important role in carcinogenesis and cancer metastasis, yet its role in the development of gastric cancer has not been well illustrated. In this study, we detected MTSS1 expression and explored its clinical significance in gastric cancer.
Immunohistochemistry was performed using tissue microarrays containing gastric adenocarcinoma specimens from 1,072 Chinese patients with normal adjacent mucosa, primary gastric cancer and lymph node (LN) metastasis and specific antibody against MTSS1. MTSS1 mRNA and protein expression were detected by reverse transcription-polymerase chain reaction and Western blotting. The clinical follow-up was done in the 669 patients living in Shanghai that was chose from the 1072 cases.
Complete loss of MTSS1 expression was observed in 751 cases (70.1%) of the 1,072 primary tumors and 103 (88%) of 117 nodal metastases; and loss of MTSS1 expression was significantly associated with poorly differentiated tumors, large tumor size, deep invasion level, the presence of nodal metastases and advanced disease stage. Moreover, multivariate analysis demonstrated that loss of MTSS1 expression correlated significantly with poor survival rates (RR = 0.194, 95% CI = 0.144-0.261, P < 0.001).
MTSS1 expression decreased significantly as gastric cancer progressed and metastasized, suggesting MTSS1 may serve as a useful biomarker for the prediction of outcome of gastric cancer.
BMC Cancer 01/2010; 10:428. · 3.01 Impact Factor
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ABSTRACT: We determined the expression of mammalian target of rapamycin (mTOR) and its activated form, p-mTOR, in Chinese patients with gastric cancer and its clinical effects and underlying mechanisms.
Tissue microarray blocks containing gastric cancer tissue and matched noncancer gastric tissue specimens obtained from 1,072 patients were constructed. Expression of total mTOR and p-mTOR in these specimens was analyzed using immunohistochemical studies and confirmed by Western blotting.
The overall rates of total mTOR and p-mTOR overexpression were 50.8% (545 of 1,072) and 46.5% (499 of 1,072), respectively. The p-mTOR overexpression was significantly correlated with total mTOR overexpression. Overexpression of total mTOR protein was significantly correlated with tumor differentiation, T1/T2 tumors, and stage I/II/III disease, whereas p-mTOR overexpression was significantly correlated with lymph node metastasis and all stage disease. The Cox proportional hazards model revealed that the overexpression of p-mTOR, but not total mTOR, was an independent prognostic factor for gastric cancer. The overexpression of p-mTOR also predicted the angiogenic phenotype of human gastric cancer and regulated angiogenesis of gastric cancer cells.
Increased activation of mTOR is frequent in human gastric cancer and overexpression of p-mTOR is an independent prognostic factor, suggesting that mTOR pathway could be a potential target for therapy of this malignancy.
Clinical Cancer Research 03/2009; 15(5):1821-9. · 7.74 Impact Factor
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ABSTRACT: Annexin A1 (ANXA1) is a calcium- and phospholipid-binding protein that has been implicated in the regulation of inflammation, cell proliferation, and apoptosis. Its role in tumor development and progression is controversial, whereas its role in gastric cancer is unknown. We investigated ANXA1 expression and determined its clinical significance in gastric cancer.
Tissue microarray blocks containing primary gastric cancer, lymph node metastasis, and adjacent normal mucosa specimens obtained from 1,072 Chinese patients were constructed. Expression of ANXA1 in these specimens was analyzed using immunohistochemistry. Complete loss of ANXA1 expression was observed in 691 (64%) of the 1,072 primary tumors and 146 (86%) of 169 nodal metastases. Loss of ANXA1 expression was significantly associated with advanced T stage, lymph node metastasis, advanced disease stage, and poor histological differentiation. Loss of ANXA1 expression correlated significantly with poor survival rates in both univariate and multivariate analyses.
ANXA1 expression decreased significantly as gastric cancer progressed and metastasized, suggesting the importance of ANXA1 as a negative biomarker for gastric cancer development and progression.
Clinical and Experimental Metastasis 07/2008; 25(7):695-702. · 3.52 Impact Factor
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ABSTRACT: ObjectiveTo detect the expression of KiSS-1 and S100A4 in the primary tumor tissues and lymphatic and visceral metastases and investigate
its role in tumorigenesis and metastasis of gastric cancer.
MethodsThe protein expression of KiSS-1 and S100A4 in lymphatic and visceral metastases from advanced gastric cancer specimens was
mainly examined by immunohistochemical staining and tissues microarray.
ResultsImmunohistochemical staining revealed reduced expression of KiSS-1 and up-regulated expression of S100A4 in lymph node and
visceral metastases. Rates of KiSS-1 expression in normal tissues, primary tumor tissues, lymph node and visceral metastases
were 95.8%, 74.6%, 60.9% and 57.5%. S100A4 expression in associated cases was 43.6%, 71.8%, 70.3% and 90.0%, respectively.
Significant differences in KiSS-1 expression was significantly higher in normal tissues than that in primary tumor tissues
(P<0.001). While significant differences of S100A4 expression could be seen between normal and cancer tissues (P<0.001) and between visceral and primary tumors (P<0.05).
ConclusionTumor metastasis results from gradual accumulation of abnormal genetic alterations. Down-regulation of KiSS-1 and up-regulation
of S100A4 play a critical role in metastasis of gastric carcinoma.
The Chinese-German Journal of Clinical Oncology 11/2006; 5(6):388-390.
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ABSTRACT: Lymphangiogenesis and angiogenesis are essential for cancer metastasis. The aim of this study was to assess lymphatic microvessel density and microvessel density in human gallbladder carcinoma tissues, detect their correlation with the tumor's clinical pathological properties and evaluate their utilities for resection of gallbladder tumor.
Tissue microarray blocks containing primary gallbladder cancer and adjacent normal tissue specimens obtained from 118 patients with gallbladder carcinoma were constructed. Lymphatic microvessel density and microvessel density were quantified using immunohistochemistry. Survival was determined using univariate and multivariate analysis.
Microvessel density correlated with tumor stage and liver metastasis (p < 0.01). Lymphatic microvessel density correlated with tumor stage (p < or = 0.01) and lymph node metastasis (p < or = 0.05).There was a very weak correlation between microvessel density and lymphatic microvesseldensity (p < 0.05, r = 0.282). In univariate and multivariate analysislymphatic microvessel density and microvessel density were independent prognostic factors.
Lymphangiogenesis and angiogenesis played important rolein theprocesses of metastasis of gallbladder carcinoma. Measurements of lymphatic microvessel density and microvessel density can be used to estimate gallbladder cancer metastatic risk and provide some useful information for gallbladder carcinoma surgery.
Hepato-gastroenterology 58(105):20-5. · 0.66 Impact Factor
