Aimin Leng

Xiangya Hospital of Central South University, Ch’ang-sha-shih, Hunan, China

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Publications (5)11.05 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Clinical trials of suicide gene therapy have achieved limited success, which suggests a need for improvement. Angiogenesis plays a crucial role in the progression of cancers, which is greatly regulated by vascular endothelial growth factor (VEGF).The current study was designed to evaluate the anti-tumor effects of VEGF siRNA in combination with fusion suicide gene yCDglyTK. Introduction of a VEGF-targeted small hairpin RNA (shVEGF) to CDTK/5-FC system could induce cell apoptosis more effectively and decrease micro vessel density in xenograft tissue, thus resulted in a significant tumor growth delay in SGC7901 xenografts. These findings for the first time suggest the potential of combination gene therapy using suicide gene therapy and anti-angiogenesis gene therapy.
    Experimental and Molecular Pathology 08/2011; 91(3):745-52. · 2.13 Impact Factor
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    ABSTRACT: The strategies for tumor-specific expression of suicide genes and target tumor angiogenesis have been tested in tumors. However, the anti-tumor efficacy of the combination of these two strategies, particularly, delivering suicide gene and anti-angiogenesis agent by nanoparticles, has not yet been evaluated in colon carcinoma. We constructed a cassette to silence VEGF-A expression and express a fused yCDglyTK gene driven by tumor-specific promoter (shVEGF-CDTK). The DNA carrying shVEGF-CDTK was delivered into colon carcinoma cells by calcium phosphate nanoparticles (CPNPs). Cell proliferation was measured by MTT assay, and apoptosis was detected by flow cytometry. The anti-tumor effect of the combined cassette was tested in xenograft animal model. With 5-fluorocytosine (5-FC), CPNP-delivered shVEGF-CDTK DNA (CPNP-shVEGF-CDTK) showed high expression of fused yCDglyTK gene and effectively silenced VEGF-A expression in vitro and in vivo, which significantly inhibited colon carcinoma cell proliferation and induced apoptosis in vitro. With 5-FC, the systemic delivery of CPNP-shVEGF-CDTK significantly inhibited tumor growth in the colon carcinoma xenograft animal model. The combined cassette is obviously effective in inhibiting tumor cell proliferation and inducing apoptosis in vitro and tumor growth in vivo than the CPNP-shVEGF or CPNP-CDTK alone. The combination of VEGF-A-silencing and tumor-specific expression of suicide gene is an effective strategy for colon carcinoma treatment.
    Tumor Biology 07/2011; 32(6):1103-11. · 2.52 Impact Factor
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    ABSTRACT: Hedgehog signaling pathway plays an important role in normal mammalian gastrointestinal development and is implicated in the oncogenesis of various tumors. However, its correlation with progression and prognosis of colon cancer has not been well documented. This study was designed to investigate expression patterns of related proteins in hedgehog signaling pathway in colon cancer to elucidate its prognostic value in this tumor. Using human colon cancer and their corresponding non-diseased colon from 228 patients' biopsies, the expression of sonic hedgehog, its receptor Patched, and downstream transcription factor Gli1 was investigated by immunohistochemical staining to assess their association with the clinicopathological characteristics of colon cancer. Disease-free survival and overall survival were examined by Kaplan-Meier estimates and the log-rank test. Prognostic factors were determined by multivariate Cox analysis. One hundred and thirty-eight patients (59.6%) had sonic hedgehog-positive tumors and that the disease-free survival (43.5 vs. 73.3%, P < 0.001), and overall survival rates (50.7 vs. 88.9%, P < 0.001) of patients with sonic hedgehog-positive tumors were much lower than those of patients with sonic hedgehog-negative tumors. In addition, 163 patients (71.5%) had Patched-positive tumors, and the disease-free survival (41.7 vs. 76.9%, P < 0.001) and overall survival rates (55.2 vs. 80.0%, P = 0.002) of patients with Patched-positive tumors were also lower than those of patients with Patched-negative tumors. Moreover, positive Gli1 expression had a bad effect on the disease-free survival (41.9 vs. 73.2%, P < 0.001) and overall survival rate of patients with colon cancer (50.0 vs. 89.3%, P < 0.001). In a multivariate analysis, sonic hedgehog, Patched, and Gli1 status were indicators for poor disease-free survival and overall survival. These results have shown that the increasing expression of sonic hedgehog, Patched, and Gli1 are indicators for a poor prognosis in patients with colon cancer. This is the first report describing about the relationship between hedgehog signaling pathway and the prognosis of colon cancer.
    Medical Oncology 03/2011; 29(2):1010-6. · 2.14 Impact Factor
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    ABSTRACT: The aim of this paper was to identify novel proteins involved in the development of gastric cancer (GC). Isobaric tags for relative and absolute quantification (iTRAQ) analysis was adopted to separate the differentially expressed proteins between normal gastric epithelial cell line GES-1 and GC cell line SGC7901. Western blotting was utilized to validate the increased expression of sorcin in SGC7901; immunohistochemistry was performed to investigate its relationship with clinicopathological features of GC. Twelve differential proteins were identified. Seven proteins were found to be significantly upregulated (≥two-fold), while five proteins were markedly downregulated (≤0.5-fold), in SGC7901 cells. Sorcin was detected by this proteomic approach with a 5.4-fold upregulation in SGC7901. Western blotting and immunohistochemistry confirmed the overexpression of sorcin in GC. Immunohistochemistry showed us that sorcin was overexpressed in 55 samples of GC tissue (55/85, 64.71%) and was related closely to the depth of invasion, TNM stage, and lymph node metastasis of GC (P<0.05). The development of GC is regulated by multiple genes. Sorcin will be a novel molecular biomarker for the diagnosis, treatment, and prognosis of GC.
    Medical Oncology 11/2009; 27(4):1102-8. · 2.14 Impact Factor
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    ABSTRACT: 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.
    Experimental and Molecular Pathology 03/2009; 87(1):48-53. · 2.13 Impact Factor

Publication Stats

24 Citations
269 Views
11.05 Total Impact Points

Institutions

  • 2011
    • Xiangya Hospital of Central South University
      Ch’ang-sha-shih, Hunan, China
  • 2009–2011
    • Central South University
      • Department of Gastroenterology
      Changsha, Hunan, China