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ABSTRACT: To determine the maximum tolerated dose (MTD) of three-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT) combined with transcatheter arterial chemoembolization for locally advanced hepatocellular carcinoma.
Patients were assigned to two subgroups based on tumor diameter: Group 1 had tumors <10 cm; Group II had tumors ≥10 cm. Escalation was achieved by increments of 4.0 Gy for each cohort in both groups. Dose-limiting toxicity (DLT) was defined as a grade of ≥3 acute liver or gastrointestinal toxicity or any grade 5 acute toxicity in other organs at risk or radiation-induced liver disease. The dose escalation would be terminated when ≥2 of 8 patients in a cohort experienced DLT.
From April 2005 to May 2008, 40 patients were enrolled. In Group I, 11 patients had grade ≤2 acute treatment-related toxicities, and no patient experienced DLT; and in Group II, 10 patients had grade ≤2 acute toxicity, and 1 patient in the group receiving 52 Gy developed radiation-induced liver disease. MTD was 62 Gy for Group I and 52 Gy for Group II. In-field progression-free and local progression-free rates were 100% and 69% at 1 year, and 93% and 44% at 2 years, respectively. Distant metastasis rates were 6% at 1 year and 15% at 2 years. Overall survival rates for 1-year and 2-years were 72% and 62%, respectively.
The irradiation dose was safely escalated in hepatocellular carcinoma patients by using 3DCRT/IMRT with an active breathing coordinator. MTD was 62 Gy and 52 Gy for patients with tumor diameters of <10 cm and ≥10 cm, respectively.
International journal of radiation oncology, biology, physics 02/2011; 79(2):496-502. · 4.59 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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ABSTRACT: Pancreatic cancer with liver metastases has a poor prognosis and the molecular mechanisms remain unclear. In this study, SW1990HM, a highly metastatic human pancreatic carcinoma line was subcloned from SW1990 by intrasplenic injection. In vivo and in vitro tumorigenicity, metastatic potential, in vitro invasion, cell growth curves, plate efficiency and S-phase cell numbers were higher in SW1990HM cells. Gene expression profiles of SW1990HM and SW1990 cells showed 40 metastasis-related genes expressed with a 3-fold difference. Thirteen of these 32.5% (13/40) were adhesion and extracellular-matrix related and twelve 30% (12/40) were cell growth and proliferation related, such as MMP10, MMP9, MMP7, CDH1, MGAT5, CTNNA1, IGF1, IL8RB, ITGA7, MDM2, MET, SSTR2 and VEGF, which were related to the onset and progression of tumor metastasis. Thus, SW1990HM is an attractive model to study metastasis and identify potential therapeutic targets.
Cancer letters 05/2009; 283(1):84-91. · 4.86 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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ABSTRACT: To evaluate the response and tolerance in hepatocellular carcinoma (HCC) patients treated by three-dimensional conformal radiotherapy (3DCRT) combined with. transcatheter arterial chemoembolization (TACE).
Fourty-six HCC patients confirmed by cytology or histology were studied. All patients underwent TACE 1 to 3 courses. Then they received 3DCRT after an interval of about one month. 3DCRT was given with the field covering the tumor with a generous margin. 6 MV X-ray was used. The total dose was 30 - 54 Gy, in daily 2 Gy fractions. Immediate response was recorded according to the WHO criteria carried out by serial CT scan one month after 3DCRT. Irradiation toxicities were scored by the RTOG criteria. Acute liver toxicity was graded according to the common toxicity criteria (CTC) of National Cancer Institute. Late toxicity was focused on radiation-induced liver disease (RILD).
Partial response was observed in 8 (17.4%) patients. Stable disease and progressive disease was observed in 35 (76.1%) patients and 3 (6.5%) patients, respectively. No complete response was observed at the time of the response evaluation. The overall survival rate at 1-, 2- and 3-year was 60.9%, 39.1% and 28.3%, respectively, with a median survival period of 16 months. The 1-, 2- and 3-year local progression-free rate was 73.9%, 56.5% and 39.1%, respectively. The 1-, 2- and 3-year distant metastasis rate was 15.2%, 21.7% and 34.8%. Univariate analysis showed that favorable prognostic predictors for survival were: T3 stage, CACA 2001 stage I, absence of portal thrombosis, Child-Pugh grade A and irradiation dose of >45 Gy. Irradiation dose and liver cirrhosis were identified by Cox-regression analysis as independent predictors for survival. Two patients experienced CTC grade 1 acute hepatic toxicity and three patients experienced grade 3 acute hepatic toxicity. Two patients developed RILD. Three patients experienced RTOG grade 1 acute gastrointestinal complication and one patient experienced acute gastrointestinal bleeding. Five patients experienced RTOG grade 1 leucopenia, and five patients experienced grade 2 leucopenia.
3DCRT combined with TACE is safe and effective for HCC. It is worthy of a further dose escalation study.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 03/2006; 28(3):222-6.
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ABSTRACT: To investigate the efficacy of transcatheter arterial chemoembolization (TACE) combined with radiotherapy for unresectable large hepatocellular carcinoma (HCC).
From June 1994 to June 1999, a total of 76 patients with large unresectable HCC were treated with TACE followed by external-beam irradiation. 89 patients with large HCC, who underwent TACE alone during the same period, served as the control group. Clinical features, therapeutic modalities, acute effects and survival rates were analyzed and compared between TACE plus irradiation group and TACE alone group. A multivariate analysis of nine clinical variables and one treatment variable (irradiation) was performed by the Cox proportional hazards model.
The clinical features and therapeutic modalities except irradiation between the two groups were comparable (P>0.05). The objective response rate (RR) in TACE plus irradiation group was higher than that in TACE alone group (47.4 % vs 28.1 %, P<0.05). The overall survival rates in TACE plus irradiation group (64.0 %, 28.6 %, and 19.3 % at 1, 3, 5 years, respectively) were significantly higher than those in TACE alone group (39.9 %, 9.5 %, and 7.2 %, respectively, P=0.0001). Cox proportional hazards model analysis showed that tumor extension and Child grade were significant and were independent negative predictors of survival, while irradiation was an independent positive predictor of survival.
TACE combined with radiotherapy is more effective than TACE alone, and is a promising treatment for unresectable large HCC.
World Journal of Gastroenterology 08/2003; 9(8):1697-701. · 2.47 Impact Factor
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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
