[show abstract][hide abstract] ABSTRACT: Overexpression of the sonic hedgehog (SHH) signaling pathway is an essential characteristic of pancreatic cancer stem cells (PCSCs) and arsenic trioxide (ATO) is described as a SHH inhibitor. This study evaluates whether ATO has the potential to inhibit viability of PCSCs via binding to SHH-Gli proteins.
Cell counting kit-8 and flow cytometry were used for analyzing apoptosis in cells in vitro. The animal model was an athymic nude mouse model bearing subcutaneous xenografts of SW1990 pancreatic cancer cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry were used for tumor tissue analysis. The interaction between Gli1 and ATO was examined by a confocal system and an ultraviolet absorption spectrum assay.
ATO induced apoptosis in pancreatic cancer cells, especially CD24(+)CD44(+) cells in vitro. Combination treatment of ATO and low dose gemcitabine inhibited tumor growth by 60.9% (P = 0.004), and decreased the expression of CD24, CD44, and aldehyde dehydrogenase 1 family, member A1 significantly in vivo. ATO changed the structure of the recombinant Gli1 zinc finger peptides in a cell-free condition and the binding action of ATO to recombinant Gli1 was observed in cultured pancreatic cancer cells.
ATO may have the potential to inhibit viability of PCSCs via binding to SHH-Gli proteins in vitro and in vivo.
OncoTargets and Therapy 01/2013; 6:1129-38. · 2.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: The relationship among Quepen (ST 12), meridians that run through Quepen(ST 12) and primary lesion of tumor that metastasized to supraclavicular lymph node [the location of Quepen (ST 12)] are analyzed on the basis of the meridians-collaterals theory, investigation on literature and clinical practice and the clinical feature that varies primary tumor are always bound to supraclavicular lymph node metastasis. Integrated with clinical practice, the function and clinical significance of meridians and collaterals in treating cancer are preliminarily put for ward. The tumor and it's metastasis that locate in the regions where the meridians run through are taken into consideration in acknowledging and treating disease.
Zhongguo zhen jiu = Chinese acupuncture & moxibustion 12/2012; 32(12):1099-102.
[show abstract][hide abstract] ABSTRACT: To compare different Chinese medicine (CM) therapeutic methods on the pancreatic orthotopic transplantation tumors in nude mice, and to explore their features.
The pancreatic orthotopic transplantation tumor model was established. Sixty nude mice were randomly divided into four group, i. e., the blood circulation activating and stasis resolving group, the heat clearing and dampness removing group, the Pi-strengthening and qi-regulating group, the phlegm reducing and mass resolving group, the normal control 1 group, and the normal control 2 group, 10 in each group. 0.2 mL corresponding CM decoction or normal saline was respectively administered to each group by gastrogavage, once daily, for totally 28 days. The body weight, the tumor weight, and the tumor inhibition ratio were observed.
The tumor inhibition ratio was 42.69% in the heat clearing and dampness removing group, 31.24% in the blood circulation activating and stasis resolving group, 2.11% in the Pi-strengthening and qi-regulating group, and -12.95% in the phlegm reducing and mass resolving group. There was statistical difference in the tumor weight between the heat clearing and dampness removing group and the normal control 1 group (g, 0.51 +/- 0.28 vs 0.90 +/- 0.25, P < 0.05). There was no statistical difference in the body weight change between the two groups (P > 0.05).
The CM pathogenesis of pancreatic carcinoma may possibly due to the accumulation of dampness and heat, or the accumulation of dampness, heat, and toxicity. Clearing heat and removing dampness may be the basic principle for its treatment.
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban 05/2012; 32(5):657-60.
[show abstract][hide abstract] ABSTRACT: Smoothened (SMO) is a member of sonic hedgehog homology (SHH) signaling pathway. It plays a key role as a bridge between patched-1 (PTCH-1) and Gli. Aberrant SHH expression can be detected in various malignant tissues, and the expression in pancreatic cancer stem cells is higher apparently. SHH signals are closely associated with self-duplication of cancer stem cells, formation of tumor vessels as well as matrixes. SMO antagonists such as cyclopamine, GDC-0449 and so on show potential to inhibit activity of SHH signaling, and arrest the growth as well as metastases of tumors. Recently, a few of SMO antagonists have been studied in phase I clinical trials and some are in phase II, meanwhile, phase I or II trials of SMO antagonists to treat pancreatic cancer are performed currently. As the classical SMO antagonist, cyclopamine is extracted from a medicinal plant. Perhaps researchers may be able to determine more effective SMO-targeting drugs from herbal medicines in the future.
Journal of Chinese Integrative Medicine 03/2012; 10(3):256-63.
[show abstract][hide abstract] ABSTRACT: To observe the effects of Qingyihuaji formula (QYHJ) on the progression of liver metastases from human pancreatic cancer and to detect the expression changes of some biological factors associated with angiogenesis and metastasis during the development of advanced pancreatic cancer.
Nude mice were inoculated intrasplenically with human pancreatic cancer cell line SW1990 and then randomly assigned into 4 groups: a control group and groups QYHJ-A, QYHJ-B, and QYHJ-C. Following this, the mice were treated with or without QYHJ formula for 4 weeks and were sacrificed at the end of the sixth week. The changes in body weight were observed, followed by the livers being excised and weighed. Then, both the numbers and the volume of metastatic nodules per liver were evaluated. Subsequently, the expressions of MMPs, VEGF, and Cyr61 in the tissue of liver metastases were detected by reverse transcription polymerase chain reaction, immunohistochemistry, or Western blot. Finally, the correlation was evaluated between the expressions of the factors associated with metastasis and the growth of liver metastasis.
Liver metastases were identified in 11 of 15 mice (73%) in the control group, 9 of 15 mice (60%) in group QYHJ-A, 6 of 14 mice (43%) in group QYHJ-B, and 8 of 14 mice (57%) in group QYHJ-C both the number and the volume of metastatic nodules per liver same as the ratio of liver-body weight in QYHJ groups were significantly less than the controlled group (P < 0.05). The expressions of Cyr61, MMP-2, and VEGF at the levels of mRNA and protein were decreased in the QYHJ groups when compared with the control, as confirmed by immunohistochemistry detection (P < .05). However, no significant difference was observed in the mRNA expression of MMP-1 and MMP-9 between the QYHJ groups and the control group (P > .05). Regression analysis indicated that QYHJ possessed an evident inhibition against the progression of liver metastasis by downregulating the expression of VEGF and Cyr61 rather than MMP-2.
The QYHJ formula exerted an inhibitory effect on the growth of liver metastasis from pancreatic cancer, perhaps by targeting VEGF and Cyr61 to some extent.
Integrative Cancer Therapies 03/2011; 11(1):37-47. · 2.35 Impact Factor
[show abstract][hide abstract] 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
[show abstract][hide abstract] 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.
[show abstract][hide abstract] ABSTRACT: Traditional Chinese medicine (TCM) syndromes (ZHENG in Chinese) are the abstraction from the comprehensive analysis of clinical information gained by the four main diagnostic TCM methods: observation, listening, questioning, and pulse analyses. Proper TCM diagnosis is the most important principle to guide the prescribing of Chinese herbs.
To evaluate the specific effect of TCM ZHENG on tumor growth and to examine the molecular mechanisms underlying ZHENG and tumor growth.
The authors established subcutaneous tumor models of pancreatic cancer ZHENG syndromes of Damp heat (Shi-Re) and Spleen deficiency (Pi-Xu). Tissue samples of the subcutaneous transplanted tumors from each model were studied versus control tumors. CCR5 and CXCR4 proteins in these tissues were assayed by immunohistochemical staining. The expression of CCR5/CCL5/CCL4/CCL3 and CXCR4/SDF-1 mRNA was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR). SDF-1, CCL4, CCL5, and CCL3, which are ligands of CXCR4 and CCR5, were examined by ELISA.
The study found that tumor models with different ZHENG were successfully established in each group; the tumor growth of Shi-Re group was slower than that of the control group. It was found that there was a significant difference in CCR5 mRNA expression levels among the Pi-Xu, Shi-Re, and control groups. The results of immunohistochemistry staining revealed that the positive rate of CCR5 protein in Shi-Re group, Pi-Xu group, and control group was 25.00%, 53.33%, 83.33%, respectively. The Shi-Re group expressed the lowest levels of CCL5 and CCL4.
The results of the study suggest that the existence of TCM ZHENG may influence the tumor growth in pancreatic cancer, which might be mediated by the expression of CCR5/CCL5/CCL4. This finding may lead to the development of TCM ZHENG as a prognostic indicator in pancreatic tumor growth.
Integrative Cancer Therapies 09/2010; 9(3):291-7. · 2.35 Impact Factor
[show abstract][hide abstract] 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.
[show abstract][hide abstract] ABSTRACT: To explore the action mechanism of action of Qingyi Huaji Formula (QYHJ), whether its inhibition on the growth of the tumor is by way of down-regulating Ski expression.
SW1990 tumor cell with low Ski expression was created by lenti-virus mediated RNA interfering technique. Tumor cells with different levels of Ski expression were subcutaneously transplanted to nude mice, and the response of cancer cells to QYHJ treatment was detected.
After QYHJ treatment, the tumor growth slowed-down significantly, with the Ski mRNA and protein expressions in tumor reduced by 39.6% and 41.3% of that in untreated tumor respectively (P < 0.05). Ski mRNA and protein expressions in the created high and low Ski expression tumor cells were 105%, 123% and 46%, 30% respectively of that in parental cells (P < 0.05). The tumor weight inhibitory rates of QYHJ on high Ski expression cells were 29.6% and 32.2%, while on low Ski expression cells, it was 16.0% to 17.8% (P < 0.05).
Ski acts as an important therapeutic target of QYHJ in treating SW1990 pancreatic cancer, and its expression status mediates different response of tumor cells to QYHJ treatment.
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban 09/2010; 30(9):942-5.
[show abstract][hide abstract] ABSTRACT: To investigate the effects of Qingyi Huaji (QYHJ) decoction, a compound traditional Chinese herbal medicine, on tumor inhibition rate and serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in nude mice with transplanted tumors of human pancreatic cancer.
The tumor-bearing mice model was established by subcutaneously inoculating with xenografts of pancreatic cancer into the right armpit of 40 BALB/c nude mice. After successful modeling, the mice were randomly divided into untreated group (Arabic gum), capecitabine group, low-dose QYHJ decoction group (36 g/kg) and high-dose QYHJ decoction group (72 g/kg), with 10 mice in each group. Citrate buffer solution (containing 5% Arabic gum), capecitabine suspension and QYHJ decoction were administered to four groups by gavage respectively. After 5-week treatment, the concentrations of serum IL-6, IL-8 and TNF-alpha were examined by enzyme-linked immunosorbent assay (ELISA) using blood sample from eye socket. Then the mice were euthanized by cervical dislocation. Tumor weight and the tumor inhibition rate were calculated.
Tumor weight in the low-dose QYHJ decoction group decreased significantly as compared with the untreated group (P<0.05). Serum levels of IL-6 and TNF-alpha in low- and high-dose QYHJ groups were extremely significantly lower than those in the untreated group (P<0.01). Serum level of IL-8 in the low-dose QYHJ group was significantly lower than that in the untreated group (P<0.05). Correlation analysis showed that transplanted tumor weight of the mice was linearly positively correlated with serum levels of IL-6, IL-8 or TNF-alpha (P<0.01).
Conventional dose of QYHJ decoction is effective in suppressing pancreatic carcinoma in nude mice. The mechanism may be related to down-regulation of serum cytokines such as IL-6, IL-8 and TNF-alpha.
Journal of Chinese Integrative Medicine 07/2010; 8(7):655-61.
[show abstract][hide abstract] 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. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Three-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT) combined with or without transcatheter arterial chemoembolization (TACE) for locally advanced hepatocellular carcinoma (HCC) has shown favorable outcomes in local control and survival of locally advanced HCC. However, intra-hepatic spreading and metastasis are still the predominant treatment failure patterns. Sorafenib is a multikinase inhibitor with effects against tumor proliferation and angiogenesis. Maintenance Sorafenib would probably prevent or delay the intrahepatic and extrahepatic spread of HCC after radiotherapy, which provides the rationale for the combination of these treatment modalities.
Patients with solitary lesion (bigger than 5 cm in diameter) histologically or cytologically confirmed HCC receive TACE (1-3 cycles) plus 3DCRT/IMRT 4-6 weeks later. Maintenance Sorafenib will be administered only for the patients with non-progression disease 4 to 6 weeks after the completion of radiotherapy. The dose will be 400 mg, p.o., twice a day. Sorafenib will be continuously given for 12 months unless intolerable toxicities and/or tumor progression. If no more than 3 patients discontinue Sorafenib treatment who experience dose-limiting toxicity after necessary dose modification and delay and/or radiation-induced liver disease in the first 15 enrolled patients, the study will recruit second fifteen patients for further evaluating safety and efficacy of treatment. Hypothesis of the current study is that Sorafenib as a maintenance therapy after combined therapy of 3DCRT/IMRT and TACE is safe and superior to radiotherapy combined with TACE alone in terms of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) in comparison to historical data.
A recent meta-analysis showed TACE in combination with radiotherapy, improved the survival and the tumor response of patients, and was thus more therapeutically beneficial. In this study, local therapy for HCC is the combination of TACE and radiotherapy. Radiation exposure as a kind of stress might induce the compensatory activations of multiple intracellular signaling pathway mediators, such as PI3K, MAPK, JNK and NF-kB. Vascular endothelial growth factor (VEGF) was identified as one factor that was increased in a time- and dose-dependent manner after sublethal irradiation of HCC cells in vitro, translating to enhanced intratumor angiogenesis in vivo. Therefore, Sorafenib-mediated blockade of the Raf/MAPK and VEGFR pathways might enhance the efficacy of radiation, when Sorafenib is followed sequentially as a maintenance modality. (ClinicalTrials.gov number, NCT00999843.).
[show abstract][hide abstract] ABSTRACT: To examine whether acupuncture can prevent prolonged postoperative ileus (PPOI) after intraperitoneal surgery for colon cancer.
Ninety patients were recruited from the Fudan University Cancer Hospital, Shanghai, China. After surgery, patients were randomized to receive acupuncture (once daily, starting on postoperative day 1, for up to six consecutive days) or usual care. PPOI was defined as an inability to pass flatus or have a bowel movement by 96 h after surgery. The main outcomes were time to first flatus, time to first bowel movement, and electrogastroenterography. Secondary outcomes were quality of life (QOL) measures, including pain, nausea, insomnia, abdominal distension/fullness, and sense of well-being.
No significant differences in PPOI on day 4 (P = 0.71) or QOL measures were found between the groups. There were also no group differences when the data were analyzed by examining those whose PPOI had resolved by day 5 (P = 0.69) or day 6 (P = 0.88). No adverse events related to acupuncture were reported.
Acupuncture did not prevent PPOI and was not useful for treating PPOI once it had developed in this population.
World Journal of Gastroenterology 01/2010; 16(1):104-11. · 2.55 Impact Factor
[show abstract][hide abstract] 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.
[show abstract][hide abstract] 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
[show abstract][hide abstract] 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. · 4.12 Impact Factor
[show abstract][hide abstract] 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.
[show abstract][hide abstract] ABSTRACT: To observe the effects of ethanol extracts of Panax notoginseng on the tumor and the liver metastasis in experimental mice grafted with B16 melanoma.
B16 melanoma was transplanted in the spleen of C57BL/6 mice. The effects of different doses of ethanol extracts of Panax notoginseng on the inhibition rate of spleen tumors and the liver metastasis were observed respectively.
The high-, medium-, and low-doses of the extracts and the interferon-alpha (IFN-alpha) can improve the quality of life of the experimental mice. The weights of spleen tumor were lower in the low- and medium-dose extracts-treated groups and the IFN-alpha-treated group than that in the normal saline (NS)-treated group (P<0.05 or P<0.01). The liver metastasis was less in the low- and medium-dose extracts-treated groups and the IFN-alpha-treated group than that in the NS-treated group (P<0.01).
The ethanol extracts of Panax notoginseng can improve the quality of life of the experimental mice and inhibit the growth of tumor and the liver metastasis.
Journal of Chinese Integrative Medicine 09/2006; 4(5):500-3.