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Jie Shen,
Jia Wei,
Hao Wang,
Guofeng Yue,
Lixia Yu,
Yang Yang,
Li Xie,
Zhengyun Zou, Xiaoping Qian,
Yitao Ding,
Wenxian Guan,
Baorui Liu
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ABSTRACT: OBJECTIVE: Personalized chemotherapy based on molecular biomarkers can maximize anticancer efficiency. We aim to investigate predictive biomarkers capable of predicting response to irinotecan-based treatment in gastric cancer. METHODS: We examined gene expression of APTX, BRCA1, ERCC1, ISG15, Topo1 and methylation of SULF2 in formalin-fixed paraffin-embedded gastric cancer tissues from 175 patients and evaluated the association between gene expression levels or methylation status and in vitro sensitivity to irinotecan. We used multiple linear regression analysis to develop a gene-expression model to predict irinotecan sensitivity in gastric cancer and validated this model in vitro and vivo. RESULTS: Gene expression levels of APTX, BRCA1 and ERCC1 were significantly lower in irinotecan-sensitive gastric cancer samples than those irinotecan-resistant samples (P < 0.001 for all genes), while ISG15 (P = 0.047) and Topo1 (P = 0.002) were significantly higher. Based on those genes, a three-gene signature were established, which was calculated as follows: Index =0.488 - 0.020x expression level of APTX + 0.015x expression level of Topo1 - 0.011 x expression level of BRCA1. The three-gene signature was significantly associated with irinotecan sensitivity (rho = 0.71, P < 0.001). The sensitivity and specificity for the prediction of irinotecan sensitivity based on the three-gene signature reached 73% and 86%, respectively. In another independent testing set, the irinotecan inhibition rates in gastric samples with sensitive-signature were much higher than those with resistant-signature (65% vs. 22%, P < 0.001). Irinotecan therapy with 20 mg/kg per week to immunodeficient mice carrying xenografts with sensitive-signature dramatically arrested the growth of tumors (P < 0.001), but had no effect on mice carrying xenografts with resistant-signature. CONCLUSIONS: The three-gene signature established herein is a potential predictive biomarker for irinotecan sensitivity in gastric cancer.
Journal of Translational Medicine 03/2013; 11(1):73. · 3.41 Impact Factor
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ABSTRACT: Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. Prognosis and treatment options are stage-dependent. Typically, prognosis of patients with unresectable HCC is poor, particularly for patients with distant metastasis. Sorafenib has demonstrated an overall survival benefit and has become the new standard of care for advanced HCC. However, in metastatic HCC, long-term progression-free survival for five years with reduced doses of sorafenib is extremely rare. In clinical practice, certain patients are discontinuing the use of this drug due to its side-effects. We highlight the importance of prolonged sorafenib administration, even at reduced doses. We describe an unusual case of a 74-year-old patient with HCC metastatic to the vertebrae that responded to a reduced dose of sorafenib and has subsequently demonstrated no signs of disease progression since starting treatment almost five years ago. This suggests that certain patients with highly progressive HCC involving bone metastasis may achieve long-term survival by reduced doses of sorafenib.
Oncology letters 01/2013; 5(1):381-385. · 0.11 Impact Factor
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ABSTRACT: Despite of the fact that a large amount of therapeutic agents have been developed for cancer treatment, we are still sometimes in a dilemma of choosing a most effective regimen for individual. With the reference of several recent researches, positive clinical correlations have been identified with primary tumor xenografts models, but limitations in existed models reveals a need for improvement. Over the past decade, conceptual progress has been made that tumors had increasingly been recognized as organs in which ostensibly normal cells as well as cancer cells participate actively in tumorigenesis by creating the "tumor microenvironment". Herein, we propose a hypothesis based on this novel conception that if transplanted as an organ, tumor implantation in nude mice would conserve most approximated biological traits with improved success rate, which make personalized tumor xenograft model practical for pre-clinical trials as substitutes for each patient. In our pilot study, intact tumor bloc was applied in implantation to evaluate this notion. As a result, 107 xenografts from all 20 patients of gastric cancer were transplanted successfully. Pathological comparison confirmed that no differences between xenografts and primary tumors while the therapeutic response to two chemotherapeutic agents, docetaxel and pemetrexed, exhibited differently. In conclusion, applying personalized primary tumor xenograft model derived from freshly excised tumor in pre-clinic trails would potentially lead to a more effective customized chemotherapy.
Medical Hypotheses 09/2012; · 1.39 Impact Factor
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Nannan Lu,
Qin Liu,
Rutian Li,
Li Xie,
Jie Shen,
Wenxian Guan, Xiaoping Qian,
Lixia Yu,
Yitao Ding,
Xiqun Jiang,
Baorui Liu
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ABSTRACT: Novel pemetrexed-loaded gelatinase-responsive nanoparticles were prepared as a targeted delivery system to determine its potential for clinical therapy of malignant melanoma. The pemetrexed-loaded poly(ethylene glycol)(PEG)-peptide-poly(ε-caprolactone) (PCL) nanoparticles included a gelatinase-cleavage peptide and a PEG-PCL-based structure. The pemetrexed-loaded PEG-peptide-PCL nanoparticles have shown the best antimetastatic effect in experimental lung metastasis models. The expressions of CD133 and thymidylate synthetase of metastatic tumors were also evaluated in our studies. Our results showed that pemetrexed-loaded gelatinase-responsive nanoparticles may represent a potent drug delivery system for inhibiting pulmonary metastasis and our preclinical results can provide new avenues for clinical therapy of malignant melanoma.
Anti-cancer drugs 07/2012; 23(10):1078-1088. · 2.23 Impact Factor
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ABSTRACT: Rhizoma Paridis, a traditional Chinese Medicine, was identified to be cytotoxic to cancer cells. The present study was designed to investigate the potential anti-angiogenic and antitumor effect of the ethanol extract of Rhizoma Paridis (RPE) in vitro and in vivo.
The cytotoxic effect of RPE against human colon cancer Lovo cells and human umbilical vein endothelial cells (HUVECs) was examined using MTT assay. We also tested the effect of RPE on tube formation, migration, apoptosis and cell cycle of HUVECs. Moreover, Lovo subcutaneous xenograft was applied to study the antitumor and anti-angiogenesis effect of RPE in vivo.
RPE exerted a higher inhibition effect on the proliferation of HUVECs than Lovo cells. The tube formation and cell migration were also significantly inhibited in the presence of RPE in a concentration-dependent manner though the significant inhibition effects were observed at the cytotoxic dose. RPE induced cell apoptosis and G0-G1 cell cycle arrest of HUVECs. In vivo, significant tumor growth inhibition was observed in human colon cancer xenografts established by Lovo cells, accompanying by a marked decrease in MVD.
Our current study exhibited that RPE has a selective cytotoxity against HUVECs comparing to Lovo cells and also demonstrated significant anti-angiogenic effect in vivo.
Journal of ethnopharmacology 06/2012; 143(1):256-61. · 2.32 Impact Factor
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ABSTRACT: Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death.
MTT assay was used to determine IC(50) values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI) method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI) double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR).
Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells.
Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.
BMC Complementary and Alternative Medicine 04/2012; 12:58. · 2.24 Impact Factor
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ABSTRACT: To investigate the antitumor effect, biodistribution and penetration in tumors of docetaxel (DOC)-loaded polyethylene glycol-poly(caprolactone) (mPEG-PCL) nanoparticles on hepatic cancer model, DOC-loaded nanoparticles (DOC-NPs) were prepared with synthesized mPEG-PCL by nano-precipitated method with satisfactory encapsulation efficiency, loading capacity and size distribution. The fabricated nano-drugs were effectively transported into tumoral cells through endocytosis and localized around the nuclei in the cytoplasm. In vitro cytotoxicity test showed that DOC-NPs inhibited the murine hepatic carcinoma cell line H22 in a dose-dependent manner, which was similar to Taxotere, the commercialized formulation of docetaxel. The in vivo biodistribution performed on tumor-bearing mice by NIRF real-time imaging demonstrated that the nanoparticles achieved higher concentration and longer retention in tumors than in non-targeted organs after intravenous injection. The immunohistochemical analysis demonstrated that the nanoparticles located not only near the tumoral vasculatures, but also inside the tumoral interior. Therefore, DOC-NPs could penetrate into tumor parenchyma, leading to high intratumoral concentration of DOC. More importantly, the in vivo anti-tumor evaluation showed that DOC-NPs significantly inhibited tumor growth by tumor volume measurement and positron emission tomography and computed tomography (PET/CT) imaging observation. Taken together, the reported drug delivery system here could shed light on the future targeted therapy against hepatic carcinoma.
International journal of pharmaceutics 04/2012; 430(1-2):350-8. · 2.96 Impact Factor
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ABSTRACT: Different chemotherapeutic agents currently available are effective only in certain subsets of patients. Predictive biomarkers will be helpful in choosing those agents and can improve the clinical efficiency by a more personalized chemotherapeutic approach. Raltitrexed is a novel water-soluble quinazoline folate analogue and can improve the efficiency of gastric cancer treatment, but its predictive biomarker remains unclear. The aim of our study was to investigate the role of plasma and tumor thymidylate synthase (TS) mRNA levels as predictive biomarkers for raltitrexed in gastric cancer. In total, 125 freshly removed gastric tumor specimens and corresponding blood samples before surgery were collected. Raltitrexed sensitivity was determined by histoculture drug response assay procedures. TS mRNA levels in tumor and plasma were determined by quantitative reverse transcription polymerase chain reaction. Plasma TS mRNA level in cancer patients was significantly higher than in healthy subjects (p = 0.009) and was significantly correlated with TS mRNA level in tumor tissues (r = 0.665, p < 0.001). Tumor and plasma TS mRNA expression levels were significantly lower in raltitrexed-sensitive group than in resistant group (p = 0.007 and 0.013, respectively). The sensitivity and accuracy of raltitrexed sensitivity prediction based on plasma TS mRNA levels were 82 and 60%, respectively, whereas the prediction based on tumor TS mRNA reached 70% sensitivity and 68% accuracy. These results indicate that TS mRNA level in plasma can mirror tumor TS mRNA level, and both of them can be used to predict raltitrexed sensitivity in gastric cancer.
International Journal of Cancer 03/2012; 131(6):E938-45. · 5.44 Impact Factor
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ABSTRACT: Paclitaxel (Ptx) has demonstrated encouraging activity in the treatment of gastric cancer. Development of drug-containing biodegradable polymeric nanoparticles (np) becomes one of the solutions to relieve side effects of Ptx. However, Ptx-loaded nanoparticles prepared by the nanoprecipitation method are unstable in the aqueous phase. Here we report that tetrandrine (Tet) effectively increases the stability of Ptx-loaded nanoparticles when Tet is coencapsulated with Ptx into mPEG-PCL nanoparticles. The current study demonstrates the synergistic antitumor effect of Tet and Ptx against gastric cancer cells, which provides the basis of coadministration of Tet and Ptx by nanoparticles. It is reported that the cellular chemoresistance to Ptx correlates with intracellular antioxidant capacity and the depletion of cellular antioxidant capacity could enhance the cytotoxicity of Ptx. Tet effectively induces intracellular ROS production. Therefore, the present study provides a promising novel therapeutic strategy basing on "oxidation therapy" that it could amplify the antitumor effect of paclitaxel by employing Tet as a pro-oxidant. More intracellular Tet accumulation by endocytosis of Ptx/Tet-np than equivalent doses of free drug leads to more intracellular ROS induction, which could efficiently enhance the cytotoxicity of Ptx by sequential inhibition of ROS-dependent Akt pathway and activation of apoptotic pathways, all of which would mediate the superior cytotoxicity of Ptx/Tet-np over free drug. The present results suggest that the codelivery of Ptx and Tet by nanoparticles provides a novel therapeutic strategy basing on "oxidation therapy" against gastric cancer.
Molecular Pharmaceutics 12/2011; 9(2):222-9. · 4.78 Impact Factor
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Jia Wei,
Carlota Costa,
Yitao Ding,
Zhengyun Zou,
Lixia Yu,
Jose Javier Sanchez, Xiaoping Qian,
Hong Chen,
Ana Gimenez-Capitan,
Fanqing Meng,
Teresa Moran,
Susana Benlloch,
Miquel Taron,
Rafael Rosell,
Baorui Liu
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ABSTRACT: Breast cancer susceptibility gene 1 (BRCA1) has a central role in chemotherapy-induced DNA damage response. The protein inhibitor of activated STAT (PIAS) family of proteins, PIAS1 and PIAS4, are also necessary for adequate DNA damage repair. To further understand the role of BRCA1 in DNA repair, we examined the mRNA expression of these genes in 133 advanced (stage III-IV) gastric cancer patients using quantitative reverse transcription polymerase chain reaction. All P values were two-sided. The median overall survival was 12.5 months (95% confidence interval [CI] = 9.8 to 13.4 months). Among 59 patients receiving second-line docetaxel, the median overall survival was 25.8 months (95% CI = 9.2 to 42.4 months) for patients with high BRCA1 expression, 19.1 months (95% CI = 3.4 to 34.8 months) for those with intermediate expression, and 9.5 months (95% CI = 8.7 to 10.2 months) for those with low expression (P = .0062). The risk of mortality was higher in patients with low BRCA1 levels compared with high BRCA1 levels (hazard ratio of death = 2.49, 95% CI = 1.03 to 5.97, P = .037). Survival in patients receiving second-line docetaxel-based chemotherapy showed a similar trend with PIAS1 and PIAS4 mRNA expression levels, although the associations for PIAS4 were not statistically significant.
CancerSpectrum Knowledge Environment 08/2011; 103(20):1552-6. · 14.07 Impact Factor
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ABSTRACT: With the development of pharmacogenomics and pharmacogenetics, personal therapy based on genes has become one of the most effective ways to enhance chemotherapeutic effect on non-small cell lung cancer (NSCLC) patients. Much attention has been paid to validate the predictive biomarkers of chemotherapy in order to guide chemotherapy and enhance effect in general. Gemcitabine is one of the common agents treating NSCLC recently. This review is mainly about the recent reports on potential biomarkers of gemcitabine in tailored therapy of NSCLC.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 05/2011; 14(5):421-8.
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ABSTRACT: Conventional polymerase chain reaction-based Sanger sequencing is the standard assay for the detection of K-Ras mutations. However, this method is deficient in identifying small numbers of mutation-bearing cells, and tumor-cell enrichment methods such as microdissection or macrodissection are labor intensive and not always achievable. We applied the recently described coamplification at lower denaturation temperature polymerase chain reaction, which amplifies minority alleles selectively, to detect K-Ras mutations directly in 29 formalin-fixed, paraffin-embedded pancreatic specimens and compared the results with those of conventional polymerase chain reaction. To avoid a false-negative result from the coamplification at lower denaturation temperature polymerase chain reaction assay, we applied a more sensitive peptide nucleic acid polymerase chain reaction method as the gold standard. Dilution experiments indicated an approximately 5-fold improvement in sensitivity with coamplification at lower denaturation temperature polymerase chain reaction-based Sanger sequencing. Conventional polymerase chain reaction detected K-Ras mutations in 11 formalin-fixed, paraffin-embedded pancreatic specimens (37.9%), whereas coamplification at lower denaturation temperature polymerase chain reaction could identify all of those mutations as well as mutations in 10 additional samples, for a total of 21 (72.4%, P = .002) of 29. Unlike peptide nucleic acid polymerase chain reaction, coamplification at lower denaturation temperature polymerase chain reaction identified all K-Ras mutations in specimens in which tumor cells accounted for at least 20% of the total. Adoption of coamplification at lower denaturation temperature polymerase chain reaction is straightforward and requires no additional reagents or instruments. The technique is a good strategy to detect K-Ras mutations selectively in formalin-fixed, paraffin-embedded tissues without tumor-cell enrichment.
Human pathology 03/2011; 42(9):1312-8. · 3.03 Impact Factor
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ABSTRACT: The study was trying to figure out the possible role of cell-free miR-24 and miR-30d as diagnostic biomarkers for malignant effusions.
A total of 110 effusion samples (28 benign and 82 malignant) were collected and cell-free total RNA was extracted. Quantitative RT-PCR was carried out to measure the expression levels of miR-24 and miR-30d, with an exogenous supplemented plant miRNA, ath-miR156a as the reference RNA.
Malignant pleural effusions had higher expression levels of cell-free miR-24 and miR-30d than benign effusions. In the ascites group, only miR-30d was found to be significantly up-regulated in the supernatant of effusions. Combination of cell-free miR-24 and miR-30d could discriminate malignant ascites from benign with improved potency comparing to single miR-30d.
Cell-free miR-30d and miR-24 are potential diagnostic biomarkers for malignant and benign effusions.
Clinical biochemistry 02/2011; 44(2-3):216-20. · 2.02 Impact Factor
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ABSTRACT: This study was designed to investigate the predictive role of 5-FU metabolic enzymes in malignant ascites. Forty-three malignant ascites were collected and primary cancer cells were isolated. Gene expression was detected by quantitative RT-PCR. We found that DPD mRNA was higher in patients with pancreatic cancers than those with gastric cancers, colon cancers, and liver cancers. Significant correlations were found between expression of DPD and TP, and between TS and OPRT. mRNA levels of TS and OPRT correlated significantly with the chemosensitivity of 5-FU. Assessing gene expression would be useful in predicting 5-FU sensitivity for patients with malignant ascites.
Cancer Investigation 02/2011; 29(2):130-6. · 1.85 Impact Factor
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ABSTRACT: Aberrant expression of microRNA-146a (miR-146a) has been reported to be involved in development and progression in various types of cancers, but its role in gastric cancer has not been fully elucidated. The purpose of this study was to investigate the levels of miR-146a expression and its function in human gastric cancer. Quantitative real-time polymerase chain reaction was used to detect the levels of miR-146a expression in gastric cancer tissue samples and cell lines. The cell growth rate of MKN-45 gastric cancer cells transfected with miR-146a mimics was examined by MTT assay. The effects of miR-146a on cell cycle and apoptosis were assessed by FACS analyses in MKN-45 cells. Thirty-six of 43 gastric cancer tissue samples (84%) showed decreased expression of miR-146a. We found low expression of miR-146a was correlated with increased tumor size (P = 0.006) and poor differentiation (P = 0.010) in gastric cancer. Overall survival time of patients with high miR-146a expression was significantly longer than that of patients with low expression of miR-146a (P = 0.011). The MTT assay showed that introduction of miR-146a inhibited cell proliferation in MKN-45 cells (P < 0.05). The proportion of apoptotic cells induced by transfection of miR-146a mimics were greater than that induced by transfection of the negative control mimics (11.9 vs. 5.9%). Our results suggested that miR-146a has potential as a novel suppressor gene in gastric cancer and its down-regulation may promote the progression of gastric cancer.
Medical Oncology 02/2011; 29(2):886-92. · 2.14 Impact Factor
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Rutian Li,
Li Xie,
Zhenshu Zhu,
Qin Liu,
Yong Hu,
Xiqun Jiang,
Lixia Yu, Xiaoping Qian,
Wanhua Guo,
Yitao Ding,
Baorui Liu
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ABSTRACT: The extracellular pH of cancer cells is lower than the intracellular pH. Weakly basic anticancer drugs will be protonated extracellularly and display a decreased intracellular concentration. In this study, we show that copolymeric nanoparticles (NPs) are able to overcome this "pH-induced physiological drug resistance" (PIPDR) by delivering drugs to the cancer cells via endocytosis rather than passive diffussion.
As a model nanoparticle, Tetradrine (Tet, Pka 7.80) was incorporated into mPEG-PCL. The effectiveness of free Tet and Tet-NPs were compared at different extracellular pHs (pH values 6.8 and 7.4, respectively) by MTT assay, morphological observation and apoptotic analysis in vitro and on a murine model by tumor volume measurement, PET-CT scanning and side effect evaluation in vivo.
The cytotoxicity of free Tet decreased prominently (P<0.05) when the extracellular pH decreased from 7.4 to 6.8. Meanwhile, the cytotoxicity of Tet-NPs was not significantly influenced by reduced pH. In vivo experiment also revealed that Tet-NPs reversed PIPDR more effectively than other existing methods and with much less side effects.
The reversion of PIPDR is a new discovered mechanism of copolymeric NPs. This study emphasized the importance of cancer microenvironmental factors in anticancer drug resistance and revealed the superiority of nanoscale drug carrier from a different aspect.
PLoS ONE 01/2011; 6(9):e24172. · 4.09 Impact Factor
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ABSTRACT: Circulating cell-free microRNAs have been identified as potential cancer biomarkers. However, the existence and the potential application of cell-free miRNAs in effusion samples are still uncertain. In order to explore the potential role of cell-free miRNA in malignant effusions, we selected 22 miRNAs differentially expressed in the serum of lung cancer patients and studied their expression levels in body cavity effusion samples.
We measured the expression of 22 miRNAs using qRT-PCR in two samples, which were pooled with 18 malignant and 12 benign effusions, respectively. After discarding 9 lowly expressed miRNAs, a panel of 13 miRNAs were measured in 29 samples (benign n = 11, malignant n = 18). We also carried out a WST-8 test to evaluate the docetaxel sensitivity of tumor cells directly isolated from 15 malignant effusions.
We compared the miRNA expression levels between benign and malignant effusions using a Mann-Whitney U test and found miR-24, miR-26a and miR-30d were expressed differently between the two groups (P = 0.006, 0.021 and 0.011, respectively). Cells isolated from effusions rich in cell-free miR-152 were more sensitive to docetaxel (r = 0.60, P = 0.016).
Collectively, our study demonstrated that cell-free miRNAs in the supernatant of effusions may aid in the diagnosis of malignancy and predict chemosensitivity to docetaxel.
BMC Cancer 10/2010; 10:591. · 3.01 Impact Factor
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ABSTRACT: MicroRNAs (miRNAs) are a class of non-coding small RNAs. They play an important role as a post-transcriptional regulator in the protein synthesis and are involved in cellular processes, such as proliferation, apoptosis, and differentiation. miRNAs give us a new perspective to understand carcinogenesis. Since the high-throughput method developed, the miRNA profiles of cancer tissues have been comprehensively studied and specific miRNAs signatures have been identified as potential biomarkers for cancer diagnosis, therapy effect prediction, and prognosis. Additionally, the exploration in cell-free miRNAs has achieved inspiring results, indicating a more applicable cancer biomarker. We made a review and tried to figure out their potential application as biomarkers in the gastrointestinal carcinomas.
Molecular and Cellular Biochemistry 08/2010; 341(1-2):291-9. · 2.06 Impact Factor
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ABSTRACT: The aim of this study was to explore predictive genes involved in docetaxel sensitivity of gastric cancer.
Microarray analysis was performed to explore various gene expression levels between parental and docetaxel-resistant cells. A panel of 11 genes selected according to microarray analysis were validated and tested further in 11 cancer cell lines, resulting in 4 genes, CXCR4, CDK6, USP15 and CDH1. Histoculture drug response assay (HDRA) was used to examine docetaxel sensitivity, while qRT-PCR was used to measure the mRNA levels of the genes in 25 surgically dissected gastric cancer specimens.
Only CXCR4 mRNA levels in gastric cancer tissues were correlated with docetaxel sensitivity (R(2)=0.23, p=0.019) and significantly higher in resistant specimens (p=0.038). AMD3100, a CXCR4 antagonist, enhanced the docetaxel cytotoxicity in vitro.
CXCR4 mRNA expression levels may be a potential predictive biomarker in gastric cancer.
Anticancer research 06/2010; 30(6):2209-16. · 1.73 Impact Factor
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ABSTRACT: The herb medicine formula "Chong Lou Fu Fang" (CLFF) has efficacy in inhibiting the proliferation of human gastric cancer in vitro and in vivo. To explore the potentially useful combination of CLFF with chemotherapeutic agents commonly used in gastric cancer therapy, we assess the interaction between CLFF and these chemotherapeutic agents in both SGC-7901 cell lines and BGC-823 cell lines using a median effect analysis and apoptosis analysis, and we also investigate the influence of CLFF on chemotherapeutic agent-associated gene expression. The synergistic analysis indicated that CLFF had a synergistic effect on the cytotoxicity of 5-fluorouracil (5-FU) in a relative broad dose inhibition range (20-95% fraction affected in SGC-7901cell lines and 5-65% fraction affected in BGC-823 cell lines), while the synergistic interaction between CLFF and oxaliplatin or docetaxel only existed in a low dose inhibition range (≤50% fraction affected in both cell lines). Combination of CLFF and chemotherapeutic agents could also induce apoptosis in a synergistic manner. After 24 h, CLFF alone or CLFF combination with chemotherapeutic agents could significantly suppress the levels of expression of chemotherapeutic agent resistance related genes in gastric cancer cells. Our findings indicate that there are useful synergistic interactions between CLFF and chemotherapeutic agents in gastric cancer cells, and the possible mechanisms might be partially due to the down-regulation of chemotherapeutic agent resistance related genes and the synergistic apoptotic effect.
Evidence-based Complementary and Alternative Medicine 10/2009; 2011:834231. · 4.77 Impact Factor
