Natural Compounds as Potential Therapeutics for Pancreatic Cancer: A Narrative Review.

Pancreatic cancer (PC) is highly malignant with a low 5-year survival rate. PC currently does not have good early diagnostic markers and responses poorly to chemotherapeutic drugs. The search for better biomarkers and developing more effective chemotherapy are important ways to improve the healthcare of PC patients. Aptamers are single-stranded nucleic acids with high binding affinity and specificity to target molecules. Many aptamers against different forms of cancer including PC have been selected for both diagnostic and therapeutic use. Aptamers can work as ligands to distinguish tumour cells from normal cells. Using cells as selection targets, the obtained aptamers have been used to discover new cancer biomarkers after identification of the binding target. Aptamers have been shown to have antagonists effect on cancer cell proliferation, apoptosis, and metastasis. In addition, aptamers have been used as carriers to deliver therapeutic agents to selectively kill PC cells. This review summarises the potential use of aptamers in the diagnosis and treatment of PC.

Camellia oil improves Aβ25-35-induced memory impairment by regulating the composition of the gut microbiota and lipid metabolism in mice

BackgroundPancreatic cancer is a deadly disease with a very low 5-year patient survival rate of 6–8%. The major challenges of eliminating pancreatic cancer are treatment resistance and stromal barriers to optimal drug access within the tumor. Therefore, effective molecular targeting drugs with high intra-tumor access and retention are urgently needed for managing this devastating disease in the clinic.MethodsThis study has used the following in vitro and in vivo techniques for the investigation of exceptional anticancer drug FL118’s efficacy in treatment of resistant pancreatic cancer: cell culture; immunoblotting analysis to test protein expression; DNA sub-G1 flow cytometry analyses to test cell death; MTT assay to test cell viability; pancreatic cancer stem cell assays (fluorescence microscopy tracing; matrigel assay; CD44-positive cell colony formation assay); human luciferase-labeled pancreatic tumor orthotopic animal model in vivo imaging; pancreatic cancer patient-derived xenograft (PDX) animal models; and toxicology studies with immune-competent BALB/cj mice and beagle dogs.ResultsOur studies found that FL118 alone preferentially killed cisplatin-resistant cancer cells, while a combination of FL118 with cisplatin synergistically killed resistant pancreatic cancer cells and reduced spheroid formation of treatment-resistant pancreatic cancer stem-like cells. Furthermore, using in vivo-imaging, we found that FL118 in combination with cisplatin strongly inhibited both drug-resistant pancreatic xenograft tumor growth and metastasis. In PDX model, we demonstrated that FL118 alone effectively eliminated PDX tumors, while FL118 in combination with gemcitabine eliminated PDX tumors that showed relative resistance (less sensitivity) to treatment with FL118. These FL118 efficacy results are consistent with our molecular-targeting data showing that FL118 inhibited the expression of multiple antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and ERCC6, a critical regulator of DNA repair, in treatment-resistant pancreatic stem-like cancer cells. Furthermore, FL118 toxicity studies in BALB/cj mice and beagle dogs indicated that FL118 exhibits favorable hematopoietic and biochemical toxicities.ConclusionTogether, our studies suggest that FL118 is a promising anticancer drug for further clinical development to effectively treat drug-resistant pancreatic cancer alone or in combination with other pancreatic cancer chemotherapeutic drugs.

Pancreatic cancer is a highly aggressive tumor. Due to the lack of characteristic symptoms, it is usually detected in the advanced stage. Resection of the tumor is possible only in 10-20% of all patients, which significantly extends and improves the quality of their life. Therefore, new diagnostic methods are sought to detect PCDA at an early stage. Biomarkers are also increasingly being used in the diagnosis of pancreatic cancer, as well as genetic testing to better identify those at risk and use screening among them. Despite the development of treatments for pancreatic cancer, it still has a low 5-year survival rate, so there is a constant need for research into more effective therapeutic modalities.

Increasing evidence uncovers the involvement of gut microbiota in the metabolism of numerous pharmaceutical drugs. The human gut microbiome harbors 10-100 trillion symbiotic gut microbial bacteria that use drugs as substrates for enzymatic processes to alter host metabolism. Thus, microbiota-mediated drug metabolism can change the conventional drug action course and cause inter-individual differences in efficacy and toxicity, making it vital for drug discovery and development. This review focuses on drug biotransformation pathways and discusses different models for evaluating the role of gut microbiota in drug metabolism. SIGNIFICANCE STATEMENT: This review emphasizes the importance of gut microbiota and different modes of drug metabolism mediated by them. It provides information on in vivo, in vitro, ex vivo, in silico and multi-omics approaches for identifying the role of gut microbiota in metabolism. Further, it highlights the significance of gut microbiota-mediated metabolism in the process of new drug discovery and development as a rationale for safe and efficacious drug therapy.

Pancreatic cancer (PC) is one of the most common causes of cancer-associated death worldwide, with a low rate of 5-year survival. Currently, the pathogenesis of PC is complicated, with no efficient therapy. Coronavirus disease 2019 (COVID-19) disease caused by severe acute respiratory syndrome coronavirus 2 further exacerbates the challenge of patients with PC. The alteration of gut microbiota caused by COVID-19 infection may impact PC progression in patients via immune regulation. The expression of inflammatory immune mediators such as interleukin (IL)-6, IL-8, and IL-10 has been found to increase in both PC and COVID-19 patients, which is associated with the disease severity and prognostic outcome. Gut microbiome serves as a critical connector between viral infection and PC. It can regulate host systemic immune response and impact the efficacy of immunotherapy. Here, we first demonstrated the features of inflammatory cytokines in both diseases and their impact on disease outcomes. Then, we demonstrated the importance of immunotherapeutic strategies. This includes the immune modulation that targets a single or dual receptors using a single agent or their combinations for the treatment of PC in patients who get infected with COVID-19. Additionally, we explored the possibility of managing the disease by regulating gut microbiome. Overall, modulation of the lung-gut-pancreases axis can boost anti-cancer immunotherapy and reduce adverse prognostic outcomes.

Pancreatic cancer is the fourth most common cause of cancer-related mortality in the United States. Pancreatic cancer is often dubbed the silent killer because it seldom causes symptoms until advanced. As a result, few pancreatic cancers are operable at diagnosis. Furthermore, pancreatic cancer is often resistant to conventional radiotherapy or chemotherapy, and the morbidity rate almost equals the mortality rate. Therefore, search for effective regimens with moderate side effects for pancreatic cancer therapy and prevention is an urgent necessity. Chinese herbal medicines have been used for centuries with demonstrated safety profiles, thus their bioactive ingredients may be effective candidates for the prevention and/or treatment of pancreatic cancer. Danshen (Salvia miltiorrhiza) has been widely adopted in the traditional Chinese medicinal preparations for treatment of cardiovascular disease with minimal side effects. In the present study, we evaluated the effect of several major Danshen components, tanshinone IIA (T2A), tanshinone I (T1) and cryptotanshinone (CT) on pancreatic cancer cells. We found that CT, T2A and T1 all showed inhibitory effects on the growth of human pancreatic cancer cell lines MIA PaCa-2 and ASPC-1 with IC50 around 30μM, 3–8μM and 3–5μM, respectively. The drug-resistant human pancreatic cancer cell line PANC-1 showed less sensitivity to CT and T2A treatment but was very sensitive to T1 treatment with IC50 around 3.5μM. The potent T1 activity against pancreatic cancer cells was associated with downregulation of several protein markers related to cell cycle (cyclin D and cyclin B) and anti-apoptosis (Bcl2 and survivin), c-myc and Aurora A and B kinases in both MIA PaCa-2 and PANC-1 cells. To further identify more potent synergistic combination effect of natural bioactive compounds against pancreatic cancer, we determined the anti-growth activity of the combination between T1 and resveratrol, a natural compound found in the skin of red grape and other fruits. T1 and resveratrol combinations consistently showed synergistic effect on inhibiting the growth of MIA PaCa-2, ASPC-1 and PANC-1 cells. Protein assays showed that the synergistic combination effect of T1 and resveratrol was associated with combined downregulation of c-myc and Aurora A protein levels, suggesting that T1 and resveratrol may inhibit the growth of pancreatic cancer cells in part via combined inhibition on the functions of c-myc and Aurora A. Aurora A is the kinase that plays a critical role in controlling mitosis and cell growth. We further confirmed if Aurora A was a functional target for the synergistic combination effect of T1 and resveratrol. Knockdown of Aurora A dramatically inhibited PANC-1 cell growth and decreased the T1 and resveratrol combination activity, suggesting that Aurora A could be one of the targets by the T1 and resveratrol combination effect. Aurora A gene promoter contains the c-myc binding site, suggesting that Aurora A may be regulated by c-myc and the inhibition of c-myc expression may be one of the causes of reduced Aurora A expression following T1 treatment. To confirm this, we treated PANC-1 cells with a c-myc inhibitor and found decreased Aurora A gene expression in a time-dependent manner, indicating the regulation of c-myc on Aurora A gene expression. Our results suggest that the T1 and resveratrol combination may serve as a novel chemopreventive regimen for effective prevention of pancreatic cancer. Supported in part by DOD (PC073988) and NCI/NIH (R21CA127794) Citation Information: Cancer Prev Res 2011;4(10 Suppl):B63.

Breast cancer is the most common malignant disease in women. In the United States, it is estimated that 252,710 women will be diagnosed with invasive breast cancer, and 40,610 women will die of breast cancer in 2017. Recent molecular-based classification categorizes the breast cancer into HER-2+, luminal-like, normal-like and basal-like breast cancer. The 12%–37% of breast cancer patients are classified into the basal-like breast cancer. The basal-like breast cancer has an unfavorable prognosis with high risk of early relapse within the first 2–5 years treatment, resulting in lower 5-year survival rate than other types of breast cancer due to lack of effective target therapy. Thus, development of novel therapeutics is urgently needed. The recent rapid expansion of genomic data greatly contributes to the understanding of disease development and progression. To translate these genetic discoveries into clinical applications, we need to develop therapeutic platforms that can specifically modulate the expression of disease-related genes in vivo. Small RNAs, such as microRNAs (miRNAs) and siRNAs function in messenger RNA silencing and post-transcriptional regulation of gene expression. Accumulating evidences have demonstrated the therapeutic potential of these small RNAs that modulate the gene expressions in many diseases including cancers. However, difficulties of in vivo delivery to specific cells have limited the potential utility of miRNA/siRNA in cancer therapy. Given the challenge of in vivo delivery, we developed a small RNAs targeting delivery platform, comprising a miRNA/siRNA sequence, a cell surface receptor-targeting DNA aptamer (a “chemical antibody”) and a complimentary passenger sequence of the miRNA/siRNA conjugated with cholesterol. These oligonucleotide sequences were heavily modified to prevent the degradation by nucleases in serum. Our newly designed delivery platform enables target-specific delivery of the small RNAs into desired cells and tissues in vivo. Our in silico gene expression analysis using data from the breast cancer and normal tissues in The Cancer Genome Atlas (TCGA) database revealed that the suppression of miR-26a expression and overexpression of a receptor tyrosine kinase, c-KIT in the basal-like breast cancer were significantly associated with disease outcome. Therefore, we hypothesized that restoration of miR-26a loss in the cancer cells using our small RNA delivery platform can inhibit the cancer growth. To test this hypothesis, we developed c-KIT targeting miR-26a delivery therapeutic using a c-KIT targeting aptamer (termed “miR-26a chimera”). This miR-26a chimera significantly inhibited the tumor growth of c-KIT+ basal-like breast cancer cells by silencing an oncogene, EZH2 in xenograft models. Interestingly, the miR-26a chimera not only enhanced the anti-tumor effect of chemotherapy (5-FU or carboplatin) in its combinational use, but also ameliorated myelosuppresive adverse effects of the chemotherapy by protecting c-Kit+ hematopoietic progenitor cells from apoptosis via silencing a pro-apoptotic gene, Bak1. By preventing the major adverse effect of chemotherapy, our new approach may allow even broader use of chemotherapeutic drugs for the advanced breast cancer. Although our study focused on breast cancer models, miR-26a as a tumor suppressor has been observed in other cancer types, including prostate cancer, pancreatic cancer and lung cancer. Likewise, the c-KIT is also widely expressed among human cancers, including gastrointestinal stromal tumors, myeloid leukemia, small-cell lung cancer, prostate cancer, pancreatic cancer, ovarian cancer and glioblastoma. Therefore, the clinical significance of our miR-26a chimera targeting c-KIT+ cancers could extend well beyond breast cancer. Besides, our targeting delivery platforms will provide not only novel therapeutics for a wide range of diseases, but also research tools to understand the roles of disease-related genes in specific tissues in vivo.

Pancreatic cancer has a high degree of malignancy and a low 5-year survival rate, and drug resistance is one of the main factors leading to poor prognosis of pancreatic cancer. Wogonin is a flavonoid drug isolated from Scutellaria baicalensis, which has certain antitumor activity. Hence the purpose of this study was to investigate whether wogonin can be used to enhance the sensitivity of pancreatic cancer to gemcitabine chemotherapy, and investigate its possible sensitization mechanism. In vitro, MTT assay showed that wogonin increased gemcitabine cytotoxicity in gemcitabine-resistant pancreatic cancer cells. In vivo, Wogonin combined with gemcitabine was found to inhibit tumor growth in orthotopic pancreatic cancer mouse model. In order to explore the sensitization mechanism, the differentially expressed genes (DEGs) of the gemcitabine-resistant cell line Panc-1 and the gemcitabine-sensitive cell line Bxpc-3 were screened through the GEO database, and 15 differentially expressed genes were obtained by intersecting with the potential targets of wogonin. Gene Ontology and KEGG enrichment analysis was performed. Bioinformatics results predicted that wogonin promoted pancreatic cancer cell apoptosis by inhibiting protein kinase B (Akt) signaling, thereby enhancing the sensitivity of gemcitabine to Pancreatic cancer. The above results were also verified by flow cytometry and Western blotting experiments. In conclusion, wogonin may enhance the sensitivity of gemcitabine by inhibiting Akt pathway.

Pancreatic cancer (PC), as the leading cause of cancer death worldwide, is one of the deadliest tumors with a very low 5-year survival rate. Therefore, it is urgent to seek new biomarkers of PC for more accurate and reliable treatments. To identify the differentially expressed miRNAs (DEM) in PC tissues, we performed the systematic microarray and qRT-PCR analyses. We found miR-196b was the top dysregulated DEM in PC tissues as compared with the corresponding adjacent tissues, and positively correlated with poor differentiation, tumor size, lymphatic invasion and TNM stage. Furthermore, the late apoptosis rate was significantly reduced, while the cell proliferation was increased in PANC-1 and ASPC-1 cell-lines after treatment with miR-196b mimics. The qRT-PCR and Western blot analysis demonstrated that the level of CADM1 in PANC-1 cells response to the alteration of miR-196b. Moreover, blockade of CADM1 could decrease the late apoptosis in PANC-1 cells as up-regulated by inhibition of miR-196b. Finally, luciferase report assay confirmed that CADM1 was the direct target gene of miR-196b. Overexpression of miR-196b in PC tissues can increase the late apoptosis of pancreatic cancer cells by targeting CADM1. These findings suggested miR-196b is a potential target for diagnosis and therapeutics of human pancreatic cancer.

Pancreatic cancer, one of the deadliest cancers with the lowest 5-year survival rate, often develops resistance to gemcitabine-based chemotherapies. The hypovascular nature of pancreatic tumors forces cancer cells to adapt to nutrient-depleted tumor microenvironments. Conventional anticancer agents targeting rapidly dividing cancer cells under nutrient-rich conditions are largely ineffective against adapted pancreatic cancer cells. Thus, targeting cancer cells under nutrient starvation, termed the "antiausterity strategy", may be effective for pancreatic cancer. This study examined nicolaioidesin C (Nic-C) derivatives as antiausterity agents. Among the 32 derivatives, Nic-15 (4n) exhibited superior cytotoxicity against MIA PaCa-2 and PANC-1 pancreatic cancer cells, inhibited MIA PaCa-2 cell migration and colony formation, and modulated the PI3K/Akt/mTOR pathway, while reducing the ER stress markers induced by gemcitabine. Nic-15 was found to inhibit tumor growth and enhance the efficacy of gemcitabine in an in vivo xenograft model. Nic-15 in combination with gemcitabine may be an effective strategy for the treatment of pancreatic cancer.

Pancreatic cancer (PC) is a seriously malignant tumor with a low 5-year survival rate. The relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and PC has been reported by several studies. However, the results were controversial. Thus, we conducted a meta-analysis to summarize available data on MTHFR gene and PC. We searched PubMed, Embase, Web of Science, Wanfang, CNKI databases prior to July 2019. Data were analyzed by RevMan 5.3 and STATA 12.0 software. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the strength of the association. Subgroup analysis, sensitivity analysis and assessment of publication bias were performed in this study. Ten articles with 17 reports (10 for C677T, 7 for A1298C) were eligible for inclusion in the meta-analysis (1864 cases and 3165 controls for C677T, and 1488 cases and 1946 controls for A1298C). Our meta-analysis detected that C677T was associated with PC for three genetic models (allele model: OR = 1.24, 95% CI: 1.00-1.53, P = 0.047; recessive model: OR = 1.39, 95% CI: 1.04-1.86, P = 0.027; homozygous model: OR = 1.60, 95% CI: 1.04-2.45, P = 0.034). In the stratified analyses according to ethnicity, source of controls and genotyping method, significant association was observed in genotyping method subgroup. For the A1298C polymorphism, no significant association was observed either in overall analysis or in subgroup analysis under all genetic models. MTHFR gene C677T rather than A1298C polymorphism may be associated with PC. Larger sample size studies should be performed to find the association between MTHFR gene and PC.

Introduction: Pancreatic cancer (PC) is a malignancy with poor prognosis and high mortality with a very low 5-year survival rate. Currently, apoptosis and autophagy are the central mechanisms of programmed cell death (PCD) that maintain cellular homeostasis and regulate cell fate. With the recent emergence of ‘ferroptosis’ as a new type of PCD and its close association with the pathophysiological processes of many diseases including tumors, it is viewed as a potential mechanism to improve systemic treatment of PC. Considering the opportunity to regulate both apoptosis and ferroptosis by a single agent, our group has developed a cancer-targeted small molecule consisting of a sigma-2 ligand (a known apoptotic inducer) delivery moiety linked to an inhibitor of the cystine importer xCT (dm-Erastin, a known ferroptotic inducer) and named it as Sigma-2-Erastin (S2E) or ACXT-3102. The study presented here is aimed at determining the efficacy of ACXT-3102 in PC and defining its underlying mechanism of action. Methods: Using in vitro and in vivo tumor xenograft models of human PC, we determined the effects of ACXT-3102 treatments in regulating PCD of PC cells and defined the signaling pathway involved in mediating the effects. Results: As assessed by TitreGlo assays, we observed dose-dependent inhibition of PC cell (BxPC-3, AsPC-1 & PANC-1) viability. Following the WES-analysis of signaling proteins, we observed that ACXT-3102 induces PC cell death by combinatorial regulation of apoptotic and ferroptotic PCD via lipid ROS-DUSP6-MAPK/ERK-mediated signaling pathway. Interestingly, the results of this study demonstrated a hyperactivation of MAPK/ERK signaling by increased phosphorylation instead of inhibition involved in inducting apoptotic cell death as represented by significant increases in expression of cleaved Capase-3/7 and PARP. In addition, ACXT-3102 treatments deceased GPX4 expression along with an increase in lipid ROS production as key markers of inducing ferroptotic cell death. Results from the murine model of human tumor xenografts using AsPC-1 cells further demonstrated significant decreases in tumor volume and increases in survival proportions in ACXT-3102-treated mice. Conclusions: ACXT-3102, an orally administered conjugate of sigma-2 ligand and Erastin induces PCD of human PC by uniquely regulating apoptosis and ferroptosis together. Therefore, ACXT-3102 offers a novel and improved therapeutic strategy for treating patients of fatal human carcinomas, especially those, which are difficult to diagnose at an early stage. Citation Format: Kumar S. Bishnupuri, Kenneth F. Newcomer, Qingqing Gong, Li Ye, Suwanna Vangveravong, Rony Takchi, Bradley T. Keller, Dirk M. Spitzer, William G. Hawkins. Sigma-2-Erastin inhibits PC tumor growth through lipid ROS-DUSP6-MAPK signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3322.

Introduction: Pancreatic cancer (PC) presents significant clinical challenges, marked by a low 5-year survival rate and frequent distant metastasis. When PC metastasizes to other organs, it leads to a notable decrease in the 5-year survival rate for PC in metastasis, dropping from 11% to 3%. Despite the effectiveness demonstrated by advanced anti-cancer therapies targeting these mutated genes, the improvement in survival rates remains modest. Another critical consideration is the rising resistance to Gemcitabine, a standard drug used for treating PC. Hence, it is imperative to gain a more profound understanding of the comprehensive mechanisms underlying metastatic pancreatic cancer (mPC) and actively explore novel drugs for its treatment. Methods: First, we reanalyzed the RNA-seq of three of PC's most common metastatic sites, including liver, lung, and peritoneum. Using the Galaxy platform, we identified DEGs (differentially expressed genes) between metastatic sites. After that, we further utilized other web-based tools and databases, such as GEPIA, TIMER 2.0, Alphafold, PubChem, Drugbank, and Chembl, to identify ANKRD22 and perform molecular docking of Fostamatinib binds to this gene. Results: Our research focused on exploring the role of ANKRD22, which contains four copies of L-shaped ankyrin motifs, an emerging oncogenic molecule associated with various cancers. In the current study, we identified that ANKRD22 exhibited significant expression in the pancreatic adenocarcinoma (PAAD) cohort, correlating with deteriorating OS rates in PC patients. Moreover, it displayed distinct expression patterns in advanced stages of the disease compared to early stages, Furthermore, we uncovered a noteworthy correlation between ANKRD22 and the Kras, TP53, CDKN2A, and SMAD4 genetic anomaly, linked to diminished survival rates, as widely recognized, in the initiation and progression of PC, these four genes stand out as the most frequently mutated. Mechanistically, ANKRD22 exhibited associations with KRAS dependency signature, U12 type spliceosome assembly, multivesicular body routing, cell invasion, tumor cell line invasion, and tumor cell line migration, all indicative of PC progression and dissemination. Expanding our investigation through the DrugBank and ChEMBL databases, we delved into fostamatinib, an FDA-approved drug known as a spleen tyrosine kinase (SYK) inhibitor. Molecular docking experiments revealed the potential interaction between ANKRD22 and fostamatinib, suggesting its candidacy to treat mPC. Conclusion: Our findings identify ANKRD22 as a pivotal oncogenic factor promoting metastasis in PC and propose fostamatinib as a potential inhibitory treatment. Citation Format: Huong Thi Luu Kim Huynh, Hendrick Gao-Min Lim, Yuan-Chii Gladys Lee, Chien-Hsin Chen, Alexander T.H. Wu. Identifying ANKRD22 and fostamatinib as a theragnostic target and drug candidate for metastatic pancreatic cancer through in silico analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 880.

Background: Pancreatic cancer is a common disease of digestive cancers. The tumor progresses rapidly and malignantly, showed a low 5-year survival rate. However, when diagnosed and treated early, the 5-year survival rate of pancreatic cancer improves significantly. Endoscopic ultrasound (EUS) has the advantage that probe can optimal access to the pancreas and surrounding organs, therefore, diagnose pancreatic tumors can be made even when the tumor is small (< 2 cm). Furthermore, Endoscopic Ultrasound- Guided Fine needle aspiration (EUS-FNA) can determine the exact histology of the tumor. Objectives: 1. Investigate some clinical, biological and endoscopic ultrasound characteristics in patients with pancreatic cancer. 2. Evaluate the relationship between endoscopic ultrasound images with clinical and biological characteristics and compare the results between endoscopic ultrasound with computer tomography. Materials and methods: Descriptive cross-sectional studies in 58 patients with pancreatic cancer had endoscopic ultrasound. Results: In 58 patients with pancreatic cancer, we recorded that patients with a history of smoking accounted for 32.8%, and drinking alcohol 31%. Abdominal pain was 89.7%, 44.8% of patients show anorexia, 37.9% have weight loss. 69% of patients had CA 19-9 > 37 UI/ml. EUS found a patient with pancreatic tumor < 2 cm, but CT scan could not detect. Tumors in pancreatic head accounted for 60.3%; in the body 24.1%, 96.6% of pancreatic cancer have a hypoechoic structure, heterogeneous ultrasound. There was a significant relation between pancreatic head tumor and other part with jaundice (p = 0.013). Compatibility in diagnosis of vascular invasion between EUS and CT scan was average (K = 0.483). Conclusion: Smoking and alcohol consumption accounted for the highest proportion, abdominal pain was the most common clinical symptom. Endoscopic ultrasound can diagnose small pancreatic tumors that CT scan can not detect. Key words: Pancreatic cancer, endoscopic ultrasound, clinical characteristics, bio-marker