The Tumor Immune Microenvironment plays a Key Role in Driving the Progression of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an epithelial cancer distinguished by bile duct cell differentiation and is also a fibroproliferative tumor. It is characterized by a dense mesenchyme and a complex tumor immune microenvironment (TME). The TME comprises both cellular and non-cellular components. The celluar component includes CCA cells, immune cells and mesenchymal cells represented by the cancer-associated fibroblasts (CAFs), while the non-cellular component is represented by mesenchymal elements such as the extracellular matrix (ECM). Recent studies have demonstrated the important role of the TME in the development, progression, and treatment resistance of CCA. These cell-associated prognostic markers as well as intercellular connections, may serve as potential therapeutic targets and could inspire new treatment approaches for CCA in the future. This paper aims to summarize the current understanding of CCA's immune microenvironment, focusing on immune cells, mesenchymal cells, ECM, intercellular interactions, and metabolism within the microenvironment.

Circulating tumor cells in gastric cancer: developments and clinical applications.

Circulating tumor cells (CTCs), which are shed from primary tumor or metastatic sites into the bloodstream and subsequently seed into distant tissues, are considered as the precursors of metastases. Gastric cancer (GC) is a highly heterogeneous malignant tumor. With regard to the diagnosis of GC, secondary pathological biopsy is difficult, while invasive examination is harmful to patients. In recent years, CTCs have made great progress in tumor diagnosis, prognosis prediction, efficacy detection and treatment guidance, but the research on the role of CTCs in GC remains limited. The following sections review the landmark studies demonstrating the technical approaches of CTCs monitoring in the field of GC. Moreover, we highlight the clinical application of CTCs numbers and phenotypes in monitoring the therapeutic efficacy and judging patient prognosis by sequential blood analyses.

m6A Methyltransferase 3 Promotes the Proliferation and Migration of Gastric Cancer Cells through the m6A Modification of YAP1.

Gastric cancer is the most common gastrointestinal tumor with an increasing incidence. Furthermore, advanced gastric cancer is more common, but the mechanism underlying the proliferation and metastasis of gastric cancer has not been thoroughly explored. N6-methyladenosine (m6A) methyltransferase 3 (METTL3) may be involved in the proliferation and metastasis of gastric cancer. Therefore, Yes-associated protein 1 (YAP1) in the Hippo pathway was selected as the target, and the relationship between METTL3 and the proliferation and metastasis of gastric cancer was proved through a series of experiments. This research showed that the expression of m6A and METTL3 was upregulated in human gastric cancer tissues and gastric cancer cell lines. After lentiviral transfection, METTL3 silencing in AGS (human gastric adenocarcinoma cell line AGS) and MKN-45 (human gastric cancer cell line MKN-45) gastric cancer cell lines directly inhibited the proliferation, aggressiveness, and migration of gastric cancer cells. Mechanically, the inhibition of the YAP1-TEAD signaling pathway by peptide 17 reduces m6A methylation and the total mRNA level of YAP1. It also eliminates the promoting effect of METTL3 on the proliferation and migration of gastric cancer cells. In turn, the overexpression of YAP1 eliminates the inhibitory effect of METTL3 silencing on the proliferation, migration, and invasion of gastric cancer cells. This article proved that m6A methyltransferase METTL3 promoted the proliferation and migration of gastric cancer cells through the m6A modification of YAP1.

Prophylaxis of neutropenia with mecapegfilgrastim in patients with non-myeloid malignancies: a real-world study.

BACKGROUND: Chemotherapy-induced neutropenia is commonly encountered in clinical practice. The management of neutropenia has been evolving from short-acting granulocyte colony-stimulating factors (G-CSFs) to long-acting G-CSFs. However, an evaluation of the safety and effectiveness of long-acting G-CSFs in clinical practice is still lacking. METHODS: This multicenter, non-interventional study was aimed at exploring the safety and effectiveness of mecapegfilgrastim in different cancer patients in China. All patients provided written informed consent prior to the study and were treated according to routine clinical practice. Different prophylactic strategies (primary or secondary prophylaxis) were also compared. RESULTS: This study included 638 patients from May 2019 to November 2020. More than half of the participants were breast cancer patients. The mean age of all the patients was 56 years. White blood cell increase (6.2%) was the most frequently reported adverse event (AE) possibly related to the study drug. No unexpected AEs were reported. Grade ≥3 neutropenia in chemotherapy treatment cycle 1 was reported in 36 (5.6%) patients. Incidence of grade ≥3 neutropenia in cycle 1 in the primary and secondary prophylaxis subgroups were of 4.3% and 9.2%, respectively. A decreasing trend of severe neutropenia incidence was observed from cycle 1 to cycle 4. CONCLUSIONS: Mecapegfilgrastim was generally well tolerated, and no unexpected AEs were observed in this study. Primary administration of mecapegfilgrastim led to a lower incidence of neutropenia than did secondary administration. Continuous administration of mecapegfilgrastim could keep the incidence of neutropenia to a relatively low level.

The Prognostic Value of the Prognostic Nutritional Index (PNI) in Radically Resected Esophagogastric Junction Adenocarcinoma.

To determine the influence of preoperative prognostic nutritional index in adenocarcinoma of the esophagogastric junction, this study was conducted to analyze 420 patients with adenocarcinoma of the esophagogastric junction who underwent surgery. A total of 120 healthy volunteers were included as the healthy control group. The cutoff values of prognostic nutritional index for predicting survival were obtained according to the receiver operating characteristic curve. The clinic-pathological feature and survival were compared between low and high prognostic nutritional index group. Results showed that the prognostic nutritional index in the patient group was lower than that in the healthy control group (P < 0.05). The level of prognostic nutritional index was significantly associated with tumor differentiation, Siewert type, tumor size, body mass index, and hemoglobin levels (P < 0.05). The level of prognostic nutritional index was negatively correlated with age of onset, tumor differentiation, Siewert type, tumor size, depth of tumor, but positively associated with the levels of body mass index and hemoglobin. Multivariate analysis revealed that prognostic nutritional index was an independent factor associated with disease-free survival (P = 0.027) and overall survival (P = 0.003). In conclusion, low prognostic nutritional index may be considered as an independent adverse prognostic marker in patients with adenocarcinoma of the esophagogastric junction.

Circulating tumor DNA detection and its application status in gastric cancer: a narrative review.

Circulating tumor DNA (ctDNA) is the small genomic fragment released by tumor cells into the circulating system, which carries the gene variation features, such as mutation, insertion, deletion, rearrangement, copy number variation (CNV) and methylation, rendering it an important biomarker. It can be used not only to diagnose certain types of solid tumors, but also to monitor the therapeutic response and explore the minimal residual disease (MRD) and resistant mutation of targeted therapy. Therefore, ctDNA detection may become the preferred non-invasive tumor screening method. For patients who cannot receive further gene detection due to insufficient or restricted sample collection with the defined pathological diagnosis, ctDNA detection can be carried out to determine the gene mutation type, with no need for repeated sampling. Gastric cancer (GC) is a malignancy with extremely high morbidity and mortality, and its genesis and development are the consequence of interactions of multiple factors, including environment, diet, heredity, helicobacter pylori infection, chronic inflammatory infiltration, and precancerous lesion. As the research on GC moves forward, the existing research mainly focuses on genetic and epigenetic changes, including DNA methylation, histone modification, non-coding RNA changes, gene mutation, gene heterozygosity loss and microsatellite instability. This paper aimed to summarize the contents of ctDNA detection, its application status in GC and clinical significance.

Value of Plasma Methylated SFRP2 in Prognosis of Gastric Cancer.

BACKGROUND: Secreted frizzled-related protein 2 (SFRP2) in circulating tumor DNA (ctDNA) is related to gastric cancer (GC) proliferation. However, whether methylated SFRP2 in ctDNA serves as the biomarker in GC patients remains unknown. AIMS: To investigate the relationship between methylated SFRP2 and the clinical outcomes of GC patients. METHODS: One hundred and forty-eight GC patients receiving systemic chemotherapy were collected during 2015-2017. Aberrant SFRP2 methylation was detected before and after chemotherapy by digital PCR-based technologies. RESULTS: Baseline SFRP2 methylation positively correlated with lymph node status (P < 0.001), distant metastasis (P < 0.001) and TNM stage (P = 0.005). The top 50% methylated SFRP2 had shorter progression-free survival (PFS) and overall survival (OS) than those with bottom 50% in stage III GC patients (median PFS, 11.0 vs. NR months; HR 13.05; 95% CI 3.05-55.95; median OS 17.0 vs. NR months; HR 7.80; 95% CI 1.81-33.60) and stage IV GC patients (median PFS, 4.0 vs. 7.0 months; HR 2.74; 95% CI 1.58-4.78; median OS 12.0 vs. 16.0 months; HR 3.14; 95% CI 1.67-5.92). Besides, the increased methylated SFPR2 from baseline to post-treatment was related to the worse PFS and OS among stage IV patients (median PFS, 5.0 vs. 7.0 months; HR 2.17; 95% CI 1.25-3.76; median OS 12.0 vs. 15.5 months; HR 3.51; 95% CI 1.94-6.35), but not to stage III patients. CONCLUSIONS: SFRP2 methylation and dynamic change are associated with GC prognosis. Our findings provide potential biomarker detection approach in ctDNA for prognosis prediction and dynamic monitoring among GC patients.

PD-L1 for gallbladder cancer: case report.

The clinical outcome of the advanced biliary tract cancer (BTC) is unfavorable, and the mortality rate is high. With local advance and metastasis, the median survival time is less than 1 year. But this patient survived 14 months with no signs of progress under treatment in our hospital. And the patient situation is stable recently. This case report can provide a treatment template for clinicians. This patient was appeared dull pain in the upper abdomen, occasionally poor defaecating. After a series of medical tests, the patient was diagnosed with advanced gallbladder cancer (GBC). This patient received chemotherapy (oxaliplatin 220 mg d1 + capecitabine 1,500 mg bid d1-14; capecitabine 1,500 mg bid d1-14; gemcitabine 1.4 g d1, 8 + capecitabine 1,500 mg bid d1-14) combined with immunotherapy (pembrolizumab 200 mg). The patient is still alive.. And there were no signs of progress. The researches on the treatment of GBC are rare, and only standard first-line treatment, lack of second-line treatment of GBC. This patient of advanced GBC received standard first-line treatment (oxaliplatin 220 mg d1 + capecitabine 1,500 mg bid d1-14; capecitabine 1,500 mg bid d1-14; gemcitabine 1.4 g d1, 8 + capecitabine 1,500 mg bid d1-14) combined with immunotherapy (pembrolizumab 200 mg), the effect is fine and is expected to contribute to the treatment of BTC.

Two novel cationic antifungal peptides isolated from Bacillus pumilus HN-10 and their inhibitory activity against Trichothecium roseum.

Public concern for food safety and environmental issues and the increase in fungicide-resistant pathogen have enhanced the interest in developing alternative methods to fungicides to control postharvest fruit decay. In this study, a bacterial strain isolated from stale potato vermicelli was identified as Bacillus pumilus HN-10 based on morphological characteristics and 16S rRNA gene sequence analysis. Furthermore, two novel cationic antifungal peptides named P-1 and P-2 were purified from B. pumilus HN-10 using macroporous adsorbent resin AB-8, Sephadex G-100 chromatography, and reversed-phase high-performance liquid chromatography. The primary structure of P-1 and P-2, which were proved to be novel antifungal peptides by BLAST search in NCBI database, was PLSSPATLNSR and GGSGGGSSGGSIGGR with a molecular weight of 1142.28 and 1149.14 Da, respectively, as indicated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Both P-1 and P-2 exhibited strong antifungal activity against Trichothecium roseum with minimum inhibitory concentrations starting from 1 µg/mL. The two novel antifungal peptides were stable below 80 °C for 2 h, but lost their activity in 15 min at 121 °C. In addition, they were resistant to the proteolytic action of pepsin, trypsin, and papain, and stable within a wide range of pH (2.0-12.0). These results showed that P-1 and P-2 are novel cationic antifungal peptides with specific activity against T. roseum.

MiR-629 promotes human pancreatic cancer progression by targeting FOXO3.

The FOXO signaling pathway has been reported to have an important role in human cancer. Expression of miR-629 was markedly upregulated in pancreatic cancer and negatively correlated with FOXO3. Therefore, exploring the regulatory mechanism of miR-629 and FOXO3 signaling may provide valuable clinical targets for pancreatic cancer therapy. In the current study, we found that overexpressing and inhibiting miR-629, respectively, enhanced and reduced the cell proliferation and metastasis of pancreatic cancer cells in vitro and in vivo compared with parental cells or cells transfected with a control vector. Furthermore, we found that miR-629 negatively regulated FOXO3 protein expression and decreased the activity of a luciferase reporter construct containing the FOXO3 3'-untranslated region. These results show that miR-629 regulates FOXO3 at the posttranscriptional level, resulting in enhanced cell proliferation and invasion of pancreatic carcinoma. Furthermore, we found that overexpressing miR-629 enhanced, while inhibiting miR-629 reduced, the stem cell-like phenotype of pancreatic cancer cells in vitro. A functional polymorphism at miR-629-binding site in the 3'-UTR of FOXO3 gene confers a decreased risk of progression in pancreatic carcinoma. Furthermore, these findings suggest that miR-629 has a vital role in promoting the development of pancreatic cancer and may represent a novel prognostic biomarker and therapeutic target.

MiR-744 increases tumorigenicity of pancreatic cancer by activating Wnt/ß-catenin pathway.

The Wnt/ß-catenin signaling pathway, commonly hyperactivated in pancreatic cancer, has been reported to play an important role in the maintenance of stemness of cancer stem cells (CSCs), which is closely related to the progression of pancreatic cancer. Therefore, exploring the regulatory mechanism in Wnt/ß-catenin signaling may provide valuable clinical targets for cancer therapy. In the current study, we demonstrated that upregulation of miR-744 in pancreatic cancer promoted Wnt/ß-catenin signaling by directly targeting secreted frizzled-related protein 1 (SFRP1), glycogen synthase kinase 3ß (GSK3ß), and transducin-like enhancer of split 3 (TLE3), important negative modulators of Wnt/ß-catenin signaling. Expression of miR-744 was markedly upregulated in pancreatic cancer and positively correlated with poor patient survival. Furthermore, we found that overexpressing miR-744 enhanced, while inhibiting miR-744 reduced, the stem cell-like phenotype of pancreatic cancer cells in vitro. Importantly, in vivo model of human-derived pancreatic xenografts showed that miR-744 upregulation enhanced the tumorigenicity of pancreatic cancer cells. These findings suggest that miR-744 plays a vital role in promoting the stem cell-like phenotype of pancreatic cancer cells, and may represent a novel prognostic biomarker and therapeutic target.

siRNA targeting survivin inhibits the growth and enhances the chemosensitivity of hepatocellular carcinoma cells.

Survivin has become an attractive anticancer therapeutic target due to its important role in tumor cell viability and its selective expression in tumor cells. In the present study, we constructed a recombinant siRNA plasmid vector against survivin and stably transfected it into HepG2 and SMMC­7721 hepatocellular carcinoma cells in vitro. Semi-quantitative RT-PCR and western blotting were used to determine the expression of survivin mRNA and protein, respectively. Tumor cell proliferation was assessed by trypan blue exclusion. We evaluated the change in caspase-3 activity, and the rate of cell apoptosis and the cell cycle distribution were analyzed by flow cytometry. Assessment of chemosensitivity was carried out by MTT assay. The results showed that transfection of survivin siRNA caused a significant inhibition of survivin mRNA and protein expression which was associated with cell growth inhibition, specific G0/G1 phase arrest, increased caspase-3 activity and enhanced chemosensitivity to cisplatin in both HCC cell lines. We suggest that suppression of survivin expression by RNAi attenuates the malignant phenotype of hepatocellular carcinoma cells, and may provide a novel approach for anticancer gene therapy.

miR-17-5p inhibitor enhances chemosensitivity to gemcitabine via upregulating Bim expression in pancreatic cancer cells.

BACKGROUND: miR-17-5p is reported to be overexpressed in pancreatic cancer, and it plays an important role in carcinogenesis and cancer progression. Gemcitabine is the standard first-line chemotherapeutic agent for pancreatic cancer, however the chemoresistance limits the curative effect. AIMS: In the present study, we investigated whether inhibition of miR-17-5p could enhance chemosensitivity to gemcitabine in pancreatic cancer cells. METHODS: miR-17-5p inhibitor was transfected to pancreatic cancer cell lines Panc-1 and BxPC3, and then cell proliferation, cell apoptosis, caspase-3 activation, and chemosensitivity to gemcitabine were measured in vitro. RESULTS: Our data showed that Panc-1 and BxPC3 cells transfected with miR-17-5p inhibitor showed growth inhibition, spontaneous apoptosis, higher caspase-3 activation, and increased chemosensitivity to gemcitabine. In addition, miR-17-5p inhibitor upregulated Bim protein expression in a dose-dependent manner without changing the Bim mRNA level, and it increased the activity of a luciferase reporter construct containing the Bim-3' untranslated region. CONCLUSIONS: These results prove that miR-17-5p negatively regulates Bim at the posttranscriptional level. We suggest that miR-17-5p inhibitor gene therapy would be a novel approach to chemosensitization for human pancreatic cancer.

Prognostic significance of miR-181b and miR-21 in gastric cancer patients treated with S-1/Oxaliplatin or Doxifluridine/Oxaliplatin.

BACKGROUND: The goal of this study is to evaluate the effectiveness of S-1/Oxaliplatin vs. Doxifluridine/Oxaliplatin regimen and to identify miRNAs as potential prognostic biomarkers in gastric cancer patients. The expression of candidate miRNAs was quantified from fifty-five late stage gastric cancer FFPE specimens. EXPERIMENTAL DESIGN: Gastric cancer patients with KPS>70 were recruited for the trial. The control group was treated with 400 mg/twice/day Doxifluridine plus i.v. with Oxaliplatin at 130 mg/m(2)/first day/4 week cycle. The testing group was treated with S-1 at 40 mg/twice/day/4 week cycle plus i.v. with Oxaliplatin at 130 mg/m(2)/first day/4 week cycle. Total RNAs were extracted from normal and gastric tumor specimens. The levels of miRNAs were quantified using real time qRT-PCR expression analysis. RESULTS: The overall objective response rate (CR+PR) of patients treated with S-1/Oxaliplatin was 33.3% (CR+PR) vs. 17.6% (CR+PR) with Doxifluridine/Oxaliplatin for advanced stage gastric cancer patients. The average overall survival for patients treated with S-1/Oxaliplatin was 7.80 month vs. 7.30 month with patients treated with Doxifluridine/Oxaliplatin. The expression of miR-181b (P = 0.022) and miR-21 (P = 0.0029) was significantly overexpressed in gastric tumors compared to normal gastric tissues. Kaplan-Meier survival analysis revealed that low levels of miR-21 expression (Log rank test, hazard ratio: 0.17, CI = 0.06-0.45; P = 0.0004) and miR-181b (Log rank test, hazard ratio: 0.37, CI = 0.16-0.87; P = 0.018) are closely associated with better patient's overall survival for both S-1 and Doxifluridine based regimens. CONCLUSION: Patients treated with S-1/Oxaliplatin had a better response than those treated with Doxifluridine/Oxaliplatin. miR-21 and miR-181b hold great potential as prognostic biomarkers in late stage gastric cancer.

Minicircle-oriP-IFNγ: a novel targeted gene therapeutic system for EBV positive human nasopharyngeal carcinoma.

BACKGROUND: Nonviral vectors are attractively used for gene therapy owing to their distinctive advantages. Our previous study has demonstrated that transfer of human IFNγ gene into nasopharyngeal carcinoma (NPC) by using a novel nonviral vector, minicircle (mc), under the control of cytomegalovirus (CMV) promoter was effective to inhibit tumor growth. However, therapies based on CMV promoter cannot express the targeted genes in cancer tissues. Previous studies indicated that the development of human NPC was closely associated with Epstein-Barr virus (EBV) and demonstrated the transcriptional enhancer function of oriP when bound by EBV protein. Therefore, the present study is to explore the targeted gene expression and the anti-tumor effect of a novel tumor-specific gene therapeutic system (mc-oriP-IFNγ) in which the transgene expression was under the transcriptional regulation of oriP promoter. METHODOLOGY/PRINCIPAL FINDINGS: Dual-luciferase reporter assay and ELISA were used to assess the expression of luciferase and IFNγ. WST assay was used to assess the cell proliferation. RT-PCR was used to detect the mRNA level of EBNA1. RNAi was used to knockdown the expression of EBNA1. NPC xenograft models in nude mice were used to investigate the targeted antitumor efficacy of mc-oriP-IFNγ. Immunohistochemistry was used to detect the expression and the activity of the IFNγ in tumor sections. Our results demonstrated that mc-oriP vectors mediated comparable gene expression and anti-proliferative effect in the EBV-positive NPC cell line C666-1 compared to mc-CMV vectors. Furthermore, mc-oriP vectors exhibited much lower killing effects on EBV-negative cell lines compared to mc-CMV vectors. The targeted expression of mc-oriP vectors was inhibited by EBNA1-siRNA in C666-1. This selective expression was corroborated in EBV-positive and -negative tumor models. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the feasibility of mc-oriP-IFNγ as a safe and highly effective targeted gene therapeutic system for the treatment of EBV positive NPC.

MicroRNA-20a overexpression inhibited proliferation and metastasis of pancreatic carcinoma cells.

The aim of this study was to investigate the effect of microRNA-20a on pancreatic carcinoma cell proliferation and invasion and to find a new effective treatment strategy for pancreatic carcinoma. MicroRNA-20a expression was determined in 10 matched normal pancreatic tissues and pancreatic carcinoma by in situ hybridization. Quantitative real-time RT-PCR was used to evaluate the expression of microRNA-20a in two pancreatic carcinoma cell lines (BxPC-3 and Panc-1) and immortal human pancreatic duct epithelial cell line H6C7. Proliferation and invasion capacity were analyzed for the cells with lentivirus-mediated overexpression of microRNA-20a both in vitro and in vivo. In addition, the regulation of signal transducer and activator of transcription proteins 3 (Stat3) by microRNA-20a was determined to elucidate the underlying mechanisms. The pancreatic cancer cell lines (Panc-1 and BxPC-3) stably overexpressing microRNA-20a showed reduced proliferation and invasion capacity in vitro and in vivo, compared with parental cells or cells transfected with a control vector. Furthermore, we found that microRNA-20a negatively regulated Stat3 protein expression in a dose-dependent manner without changing the Stat3 mRNA level and decreased the activity of a luciferase reporter construct containing the Stat3 3'-untranslated region. These results show that microRNA-20a regulates Stat3 at the post-transcriptional level, resulting in inhibition of cell proliferation and invasion of pancreatic carcinoma. It may open a new perspective for the development of effective gene therapy for pancreatic carcinoma.

ZD6474 inhibits Src kinase leading to apoptosis of imatinib-resistant K562 cells.

ZD6474 is an orally available, small-molecule tyrosine kinase inhibitor. This study explores the effect of ZD6474 on imatinib-resistant K562 cell lines, which show markedly increased SRC family kinases (SFKs) activity. ZD6474 induces growth arrest and apoptosis of imatinib-resistant and parental K562 cells, as well as inhibition of Src activity and its downstream effectors, the anti-apoptotic Bcl-2 family. ZD6474 treatment also inhibits the activity of STAT3 and reactivation of its activity results in suppression of the anti-tumor effects of SFKs inhibitors. A single oral administration of ZD6474 produced dose-dependent inhibition of imatinib-resistant K562 cells xenograft tumors. These results suggest that clinical assessment of ZD6474 against imatinib-resistant CML is warranted.

siRNA directed against survivin enhances pancreatic cancer cell gemcitabine chemosensitivity.

Survivin is known to be overexpressed in various human malignancies, including pancreatic cancer, and to cause resistance to radiation and chemotherapy, so the regulation of this molecule could be a new strategy for treating pancreatic cancer. In our study, a short interfering RNA (siRNA) plasmid expression vector against survivin was constructed and transfected into human pancreatic cancer cell lines of Panc-1 and BxPC3. The expression of survivin mRNA and protein among the stable transfected cells and the untransfected cells was detected by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot, respectively. Tumor cell growth in vitro was assessed by trypan blue exclusion. The cell cycle distribution and cell apoptosis were measured by flow cytometry. The cytotoxicity assay was measured by the MTT test. Our results showed that survivin siRNA treatment caused a specific and profound decrease of survivin mRNA and protein that was associated with decreased cell growth, spontaneous apoptosis, and a specific G0/G1 arrest. Furthermore, the suppression of survivin can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine significantly. We suggest that the RNAi against survivin gene strategy would be a potential approach to chemosensitization therapy in human pancreatic cancer.