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ABSTRACT: miR-21 expression in cancer tissue has been reported to be associated with the clinical outcome and activity of gemcitabine in pancreatic cancer. However, resection is possible in only a minority of patients due to the advanced stages often present at the time of diagnosis, and safely obtaining sufficient quantities of pancreatic tumor tissue for molecular analysis is difficult at the unresectable stages. In this study, we investigated whether the serum level of miR-21 could be used as a predictor of chemosensitivity. We tested the levels of serum miR-21 in a cohort of 177 cases of advanced pancreatic cancer who received gemcitabine-based palliative chemotherapy. We found that a high level of miR-21 in the serum was significantly correlated with a shortened time-to-progression (TTP) and a lower overall survival (OS). The serum miR-21 level was an independent prognostic factor for both the TTP and the OS (HR 1.920; 95% CI, 1.274-2.903, p = 0.002 for TTP and HR 1.705; 95% CI, 1.147-2.535, p = 0.008 for OS). The results from a functional study showed that gemcitabine exposure down-regulated miR-21 expression and up-regulated FasL expression. The increased FasL expression following gemcitabine treatment induced cancer cell apoptosis, whereas the ectopic expression of miR-21 partially protected the cancer cells from gemcitabine-induced apoptosis. Additionally, we confirmed that FasL was a direct target of miR-21. Therefore, the serum level of miR-21 may serve as a predictor of chemosensitivity in advanced pancreatic cancer. Additionally, we identified a new mechanism of chemoresistance mediated by the effects of miR-21 on the FasL/Fas pathway.
Molecular oncology 11/2012; · 4.10 Impact Factor
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ABSTRACT: Several studies have reported the change of EphB2 in a variety of carcinomas and suggested a functional relation between EphB2 and tumor progression. However, its role in human pancreatic carcinoma has not been described. The aim of this study was to evaluate the significance of EphB2 in human pancreatic carcinoma CFPAC-1 cells. A lentivirus-based RNA interference (RNAi) vector was designed, synthesized and transfected into CFPAC-1 cells to inhibit EphB2 expression. WST-8 based Colorimetric Assay Cell Counting kit 8 (CCK-8) in vitro and xenograft transplantation model in nude mice was used to evaluate cell proliferation and growth respectively. Cell-cycle and apoptosis were analyzed by flow cytometry (FCM). RT-PCR and Western blot were used to assess mRNA expression and protein levels. EphB2 expression was significantly suppressed both in mRNA and protein levels using the lentivirus-based EphB2 RNAi in CFPAC-1 cells (P<0.01, P<0.01). Silencing EphB2 stimulated cell growth in vitro (P<0.05) and proliferation in vivo (P<0.01) versus Control RNAi. EphB2 RNAi significantly increased S phase cells from 18.15 to 27.18% (P<0.05), and significantly decreased G1 phase cells from 72.93 to 57.61% compared with Control RNAi (P<0.05). In addition, decreased apoptosis was observed in CFPAC-1 EphB2 RNAi cells compared with Control RNAi cells (P<0.01). The apoptosis rate was 1.63% and 7.44%, respectively. Silencing EphB2 increased CyclinD1, cyclindependent kinase 6 (CDK6) and Bcl-2 expression in both mRNA and protein levels compared with Control RNAi. A lentivirus-based EphB2 RNAi efficiently inhibited EphB2 gene and its protein expression. Silencing EphB2 stimulated pancreatic carcinoma growth by increasing cell proliferation through G1/S phase breakthrough, which relied on a CyclinD1/CDK6 cell-cycle regulated signal. Similarly, EphB2 inhibition also reduced CFPAC-1 cells apoptosis by up-regulating Bcl-2 expression. Thus, at least in the context of pancreatic carcinoma CFPAC-1 cells, EphB2 plays a tumor suppressor role in cell proliferation and apoptosis.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 01/2011; 65(2):123-31. · 2.24 Impact Factor
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ABSTRACT: To observe the efficacy and side effects of transarterial chemoembolization (TACE) combined with sorafenib for advanced hepatocellular carcinoma (HCC).
Forty patients with HCC were treated with sorafenib (400 mg bid) after TACE. The efficacy was evaluated according to RECIST 1.1 criteria, and side effects were assessed by NCI CTC 3.0 criteria.
Among the forty cases, one case achieved complete remission (CR), seven cases achieved partial remission (PR), nineteen cases achieved stable disease (SD) and thirteen cases had progressive disease (PD). The disease control rate (DCR) was 67.5%. The overall survival time was 1 - 18 months, and 1-year survival rate was 54.0%. The major adverse events were hand-foot skin reaction, diarrhea and thrombocytopenia.
The combined therapy of TACE and sorafenib is effective and well tolerated for advanced HCC.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 09/2010; 32(9):703-5.
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ABSTRACT: Qingyihuaji formula (QYHJ) is a widely used herbal formula that has shown promising antitumor effect in the treatment of pancreatic cancer in the Cancer Hospital, Fudan University, Shanghai, China.
This research was conducted to study whether Ski acts as a therapeutic target of QYHJ formula in the treatment of SW1990 pancreatic cancer.
The expression changes of Ski mRNA and protein in SW1990 pancreatic cancer subcutaneously transplanted tumor treated with QYHJ were detected by real-time polymerase chain reaction and Western blot. Then, we established a stable transfection SW1990 cell with low expression of Ski through lentivirus-mediated RNA interference (RNAi) technique. The responses to QYHJ treatment on a subcutaneously transplanted tumor with different Ski expression statuses were evaluated. Finally, the effect of Ski downregulation on SW1990 cell biological behavior was also evaluated.
Expression of Ski mRNA and protein in SW1990 subcutaneously transplanted tumor decreased dramatically after the treatment with QYHJ. Stable transfection cells with low expression of Ski (SW1990/Ski RNAi) were created, and negative vector-transfected cells (SW1990/con RNAi) were used as controls. The tumor weight inhibitory rates of QYHJ on subcutaneously transplanted tumors formed by SW1990 or SW1990/con RNAi were 29.6% and 32.2%, respectively, whereas they were 16.0% to 17.8% when the tumors were formed by SW1990/Ski RNAi. Ski downregulation sensitized the response of SW1990 cells to TGF-beta1-induced growth inhibition in vitro. Flow cytometric analyses revealed that the percentage of cells in the G1 phase increased from 40.4% to 62.9% when Ski was downregulated. The subcutaneously transplanted tumors formed by SW1990/Ski RNAi grew much more slowly than those formed by parental and control vector-transfected cells.
Ski acts as therapeutic target of QYHJ in the treatment of SW1990 pancreatic cancer cells, and its expression status mediates different responses to QYHJ treatment.
Integrative Cancer Therapies 03/2010; 9(1):50-8. · 2.14 Impact Factor
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Peng Wang,
Zhen Chen,
Zhi-Qiang Meng,
Jie Fan,
Jian-Min Luo,
Wang Liang,
Jun-Hua Lin,
Zhen-Hua Zhou, Hao Chen,
Kun Wang,
Ye-Hua Shen,
Zu-De Xu,
Lu-Ming Liu
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ABSTRACT: Ski used to be defined as an oncogene that contributes to the resistance of tumor cells to transforming growth factor-beta (TGF-beta)-induced growth arrest. As TGF-beta has a dual effect on tumor growth with both tumor-suppressing and -promoting activity depending on the stage of carcinogenesis and the cell type, the precise role of Ski in carcinogenesis remains unclear. In this study, we show that downregulation of Ski through lentivirus-mediated RNA interference decreases tumor growth both in vitro and in vivo, yet promotes cell invasiveness in vitro, and lung metastasis in vivo in the pancreatic cancer cell line SW1990, which contain wild-type Smad4 expression, and the BxPC3 cell line, which is Smad4 deficient. We also show that the downregulation of Ski increases TGF-beta-induced transcriptional activity, which is associated with increased TGF-beta-dependent Smad2/3 phosphorylation, and results in an altered expression profile of TGF-beta-inducible genes involved in metastasis, angiogenesis and cell proliferation and epithelial-mesenchymal transition. Immunohistochemical analysis of specimens from 71 patients with pancreatic adenocarcinoma showed a significant association between overexpression of Ski and decreased patient survival time (P = 0.0024). Our results suggest that Ski may act as a tumor proliferation-promoting factor or as a metastatic suppressor in human pancreatic cancer.
Carcinogenesis 07/2009; 30(9):1497-506. · 5.70 Impact Factor
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Peng Wang,
Jie Fan,
Zhen Chen,
Zhi-Qiang Meng,
Jian-Min Luo,
Jun-Hua Lin,
Zhen-Hua Zhou, Hao Chen,
Kun Wang,
Zu-De Xu,
Lu-Ming Liu
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ABSTRACT: Whether Smad7 acts as a tumor proliferation promoting factor or as a metastatic suppressor in human pancreatic cancer remains unclear. This study aims to determine the prognostic value of Smad7 in patients with pancreatic adenocarcinoma.
Surgical specimens obtained from 71 patients with pancreatic adenocarcinoma were immunohistochemically assessed for Smad7, Ki-67, MMP2, CD34, and Smad4 expression. The relationship between Smad7 expression and the clinicopathological characteristics of patients with pancreatic adenocarcinoma were also evaluated.
Fifty-one of 71 specimens (71.8%) were Smad7 positive and 20 specimens were Smad7 negative. Negative expression of Smad7 correlated with lymph node metastasis, liver metastasis after surgery, and a poor survival rate (P = 0.0004, 0.0044, and 0.0003, respectively). We also found an inverse correlation between the expression of Smad7 and MMP2 (P = 0.0189). Multivariate analysis revealed that Smad7 expression was an independent prognostic factor [hazard ratio (HR) 0.3902; 95% confidence interval (CI) 0.1839-0.8277; P = 0.0142]. Furthermore, in both Smad4-negative and Smad4-positive groups, survival of patients with Smad7-positive tumors was significantly better than those with Smad7-negative tumors (both P < 0.0001).
We conclude that low-level expression of Smad7 in pancreatic cancer is significantly associated with lymph node metastasis, high MMP2 expression, and poor prognosis.
Annals of Surgical Oncology 01/2009; 16(4):826-35. · 4.17 Impact Factor
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Peng Wang,
Lu-ming Liu,
Zhi-qiang Meng,
Zhen Chen,
Jun-hua Lin,
Zhen-hua Zhou, Hao Chen,
Kun Wang,
Bo Ping,
Long-fu Wang,
Bo-hua Wang,
Ya-fang Huang
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ABSTRACT: To study the value of fine-needle aspiration biopsy (FNAB) in diagnosing primary liver cancer (PLC) and its major complications.
From June 1, 1985 to May 31, 2005, 2528 patients who were presented with suspected PLC underwent ultrasound-guided FNAB in the Cancer Hospital of Fudan University. The results were retrospectively reviewed.
Of those 2528 cases, there was malignancy in 2061 patients (81.53%), of which 1704 were diagnosed as primary liver neoplasms; 41 were diagnosed as metastatic carcinoma, and 316 were not further classified as primary or metastatic. No malignancy was found in 431 cases (17.05%). In 36 cases (1.42%), suspicious malignancy or anaplasia was suggested. Follow-up results showed that all the 2061 positive cases were verified to be malignant and there were no false positive cases. 163 of the 431 negative cases were verified to be malignant in the follow-ups, of which 136 cases were PLC; 28 of the 36 suspicious malignancy or anaplasia were proven to be malignant (all were PLC). The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of our FNAB for diagnosing liver malignancy were 91.52%, 100.00%, 100.00%, 59.10% and 92.44%, respectively, and 81.01% cases were diagnosed by FNAB in all the 2096 cases with PLC. Cytological examinations of the smears obtained by FNAB correctly distinguished primary and secondary malignancy in 77.49% of the patients. After FNAB, 11 patients (0.44%) had intraperitoneal hemorrhages and 5 cases (0.20%) had needle tract implantation metastases.
FNAB is important and effective for determining the malignancy potential of liver tumors, especially for PLC. Complications related to FNA were rather rare, therefore, this technique may be easily applied to clinical practice.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 11/2007; 15(10):758-62.
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Peng Wang,
Zhi-Qiang Meng,
Zhen Chen,
Jun-Hua Lin,
Zhen-Hua Zhou, Hao Chen,
Kun Wang,
Ye-Hua Shen,
Zheng-Fei Zhu,
Guang-Fa Zhao,
Hong Fu,
Lu-Ming Liu
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ABSTRACT: As the population ages, many elderly people will be diagnosed with pancreatic cancer. This study is to investigate the current survival rates for patients aged > or = 70 years diagnosed with pancreatic cancer and to identify prognostic factors, which will help in choosing optimal therapies for individual patients.
Information was gathered retrospectively for 81 patients aged > or = 70 years with pancreatic cancer. Clinical parameters, treatments received and survival curves from initial treatment were analyzed.
Overall median survival was 6.2 months. Patients who underwent surgical therapy had the best median survival rate of 26.5 months, followed by patients receiving chemotherapy (6.6 months), chemoradiotherapy (5.7 months) and best supportive care (3.4 months). Further analysis showed that the median survival of chemotherapy and chemoradiotherapy groups was 8.1 and 11.3 months for stage III, 6.2 and 3.9 months for stage IV respectively. Independent negative prognostic factor for survival were Karnofsky performance status < or = 80 and presence of distant metastases.
Long-term survival can be achieved through surgical resection in patients aged > or = 70 at early stage. Chemotherapy should be considered for patients with better expected survival. Radiation therapy should be applied for stage III patients. However, it was not associated with survival benefit for stage IV. Karnofsky performance status and distant metastases are independent prognostic factors.
Hepato-gastroenterology 55(82-83):681-6. · 0.66 Impact Factor
