Phosphoinositide 3-kinase inhibitor (wortmannin) inhibits pancreatic cancer cell motility and migration induced by hyaluronan in vitro and peritoneal metastasis in vivo.

In order to block peritoneal metastasis of pancreatic cancer cells, we have attempted to block the signal transduction pathway involving hyaluronan (HA), Src, phosphoinositide 3-kinase (PI3K) and Akt. We examined the effects of Src, PI3K and Akt inhibitors on pancreatic cancer cell motility, invasion and metastasis. The pancreatic cancer cell line SW1990, known to cause peritoneal metastasis efficiently in nude mice, was used in this study. SW1990 cells were stimulated by HA to induce Akt phosphorylation. Then, the inhibitory effects of PI3K and Src kinase inhibitors were examined. Cell motility and cell migration assays were adopted to assess the cancer cell motility and its migration capability. We also examined the therapeutic efficacies of PI3K inhibitor wortmannin on peritoneal metastasis of SW1990 cells in the nude mouse model. Stimulation of SW1990 cells by HA markedly induced the Src-PI3K-Akt signaling, thus enhancing cancer cell motility and its migration. Significantly, we found that wortmannin could exert marked inhibition of the peritoneal metastasis of SW1990 in nude mice in vivo. These findings indicate that the PI3K-Akt signaling pathway plays an essential role in peritoneal metastasis and PI3K inhibitors such as wortmannin can be novel modalities to prevent peritoneal metastasis of invasive cancers such as pancreatic cancer.

Complete extragastric growth in a giant gastrointestinal stromal tumor: report of a case.

Gastrointestinal stromal tumors (GISTs) are characterized by remarkable variability in their differentiation potential, but most of these lesions do not display convincing smooth muscle or neuronal differentiation. Here we report the case of a 65-year-old woman who underwent a perfect resection of a large submucosal tumor that displayed extragastric growth. The specimen was revealed to be an elastic soft tumor, 18 x 25 x 11 cm in size. Histologically, the tumor consisted of spindle-shaped cells, with a mitotic rate of 12 per 10 high-power fields. Immunohistochemically, the tumor showed positive staining for CD34 and c-kit but negative staining for alpha-smooth muscle actin, Desmin, and s-100 protein. From these findings, the tumor was diagnosed as an uncommitted type of GIST with high-grade malignancy. This case needs careful and long-term follow-up to monitor for signs of local recurrence or distant metastasis.

Interleukin-1alpha enhances angiogenesis and is associated with liver metastatic potential in human gastric cancer cell lines.

BACKGROUND: To better understand the underlying mechanism of liver metastasis formation in human gastric cancer, we evaluated the angiogenic capabilities of human gastric cancer cell lines with different metastatic potentials as well as the role of interleukin (IL)-1alpha in the angiogenic process. MATERIALS AND METHODS: Reverse transcription-polymerase chain reaction was used to detect the expression of IL-1alpha and vascular endothelial growth factor (VEGF) mRNA in gastric cancer cell lines with different liver metastatic potentials. Levels of VEGF secreted by human gastric cancer cells were measured by enzyme-linked immunosorbent assay. We also examined how gastric cancer cells with different metastatic potentials influence the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the Premix WST-1 cell proliferation assay system and an angiogenesis assay, respectively. RESULTS: IL-1alpha expression levels were significantly correlated with liver metastatic potential in gastric cancer cell lines. Levels of VEGF secreted by gastric cancer cells appear to be regulated by IL-1alpha through IL-1 receptor Type 1 and were correlated with liver metastatic potential. Both HUVEC proliferation and tube formation were strongly enhanced by coculture with high liver-metastatic gastric cancer cells and were enhanced to a similar extent by culture in the presence of IL-1alpha. In contrast, blockade of IL-1alpha inhibited both HUVEC proliferation and angiogenesis. CONCLUSIONS: IL-1alpha may play a role in liver metastasis of gastric cancer via enhanced vascular endothelial cell proliferation and angiogenesis.

Interleukin-2 potentiation of cetuximab antitumor activity for epidermal growth factor receptor-overexpressing gastric cancer xenografts through antibody-dependent cellular cytotoxicity.

Cetuximab, a chimeric monoclonal antibody to epidermal growth factor receptor (EGFR), has been proved to have clinically significant antitumor activity against advanced colorectal cancers, but its therapeutic activity for gastric cancers remains unclear. In the present study, we investigated the antitumor effect and action mechanism of cetuximab using EGFR high-expressing (MKN-28) and EGFR low-expressing (GLM-1) gastric cancer cell lines without gene amplification. Cetuximab showed neither significant growth inhibition nor induction of apoptosis in either cell line in vitro, and only slightly inhibited ligand-induced phosphorylation of protein kinase B and extracellular signal-regulated kinase in MKN-28 cells. In contrast, cetuximab significantly inhibited subcutaneous and intraperitoneal tumor growth of MKN-28 cells, but not GLM-1 cells, in nude mice. This antitumor activity was significantly enhanced and diminished in nude mice by treatment with interleukin-2 (IL-2) and antiasialo GM1 antibody, which can expand and deplete natural killer (NK) cells, respectively. Antibody-dependent cellular cytotoxicity (ADCC) of cetuximab, as measured by (51)Cr release assay, was significantly higher in MKN-28 than in GLM-1 cells. This ADCC activity was enhanced by IL-2 and reduced by heat-aggregate of human immunoglobulin G, an inhibitor for FcR-III of NK cells. These results suggest that cetuximab in combination with IL-2 shows significant antitumor activity against EGFR high-expressing gastric cancer mainly through NK cell-mediated ADCC. Combination therapy with cetuximab and IL-2 would thus offer a new potential therapeutic approach for a subset of EGFR-overexpressing gastric cancers.

Basement membrane proteins play an important role in the invasive processes of human pancreatic cancer cells.

BACKGROUND: The invasive interaction between cells and their matrix has important roles in tumor cell invasion. This study investigated modulation of basement membrane (BM) proteins, especially collagen IV (Coll IV), laminin, and fibronectin (FN), in invasion of human pancreatic cancer cells. Furthermore, we examined the roles of beta(1)-integrins and arginine-glycine-aspartic (RGD)-containing oligopeptide in cell-matrix interactions. MATERIALS AND METHODS: Expression of integrins were examined by reverse transcriptase-polymerase chain reaction and flow-cytometric analysis in three human pancreatic cancer cell lines (BxPC-3, PANC-1, and SW1990), respectively. To determine the effect of BM proteins, invasion assays were performed. Western blot analysis for extracellular signal-regulated kinase (ERK) was performed to investigate the involvement of ERK1/2 signaling pathways. RESULTS: BM proteins significantly enhanced the invasive behavior of pancreatic cancer cells. Pretreatment with anti-beta(1)-integrin antibody suppressed invasion into Matrigel, but RGD-containing peptide inhibited invasion, which was enhanced by Coll IV and FN, not laminin. Treatment with both RGD-containing peptide and beta(1)-integrin antibody inhibited ERK1/2 phosphorylation activated by Coll IV and FN. CONCLUSIONS: BM proteins have positive actions on the processes of pancreatic cancer cell invasion and cross-talk between BM proteins and beta(1)-integrins widely participates in the multistep processes of pancreatic cancer invasion and metastasis formation.

Posterior mediastinal angioleiomyoma: report of a case.

We describe a case of mediastinal angioleiomyoma in an asymptomatic 72-year-old man, who was admitted to our hospital for a mediastinal tumor discovered during an annual medical examination. The tumor was evaluated by computed tomography (CT) and magnetic resonance imaging (MRI). Unenhanced CT scans demonstrated a tumor that was adjacent to the descending aorta. The tumor was partially enhanced in the early phase of contrast-enhanced CT, and in the late phase there was additional tumor enhancement. With MRI, the tumor displayed a homogeneous low signal intensity on the T1-weighted image and a homogeneous very high signal intensity on the T2-weighted image. Contrast-enhanced MRI demonstrated the same enhancement pattern as CT. The examination results led to a preoperative diagnosis of posterior mediastinal hemangioma, and the patient underwent surgery. The tumor originated from the supreme intercostal vein, and was diagnosed as an angioleiomyoma by histopathologic examination. Because mediastinal angioleiomyomas are very rare, they are difficult to diagnose preoperatively. However, we believe that CT and MRI can be of significant help in the differential diagnosis.

The relationship between GDNF and integrins in human colorectal cancer cell activity.

BACKGROUND/AIMS: This study was performed to determine whether GDNF influences the expression of integrins in colorectal cancer cell lines and to elucidate the mechanisms of adhesion to and invasion of extracellular matrix (ECM) proteins. METHODOLOGY: The expression of integrin subunits and alteration of this expression by GDNF were examined by flow-cytometric analysis and cellular enzyme-linked immunosorbent assay in four human colorectal cancer cell lines. Assays to evaluate adhesion and invasion of cancer cells toward ECM proteins were conducted to investigate whether increased integrin expression affects the interaction between cancer cells and putative integrin ECM ligands. RESULTS: The RET/GFRalpha-1 receptor complex for GDNF was expressed in all four colorectal cancer cell lines. The expression of the Beta1 integrin subunit in these cells was significantly enhanced by GDNF. The enhancement and associated increase in adhesion and invasion abilities in response to by GDNF were inhibited by blocking the GDNF receptor or the integrin P1 subunit. CONCLUSIONS: In colorectal cancer, the enhancement of integrin expression by signaling through the GDNF receptor strongly influences adhesion to and invasion of ECM proteins.

Gastrointestinal stromal tumor of the rectum with liver metastasis: report of a case.

Gastrointestinal stromal tumors (GISTs) have unique immunohistochemical and molecular genetic features that set them apart from leiomyomas, leiomyosarcomas, and schwannomas. Although recurrence of GIST usually tends to develop locally or in the liver, rectal GIST reoccur predominantly at the original site of the tumor. We describe a rare case of rectal GIST with multiple liver metastases. We carried out immunohistochemical staining for p53 protein, proliferating cell nuclear antigen (PCNA), integrins, and interleukin-1 receptor type I (IL-1RI) in order to investigate the degree of malignancy of this neoplasm in addition to the immunohistochemical analyses that were necessary for diagnosing GIST. Histologically, the rectal tumor was classified as an uncommitted type of rectal GIST with multiple liver metastases. Positive immunostaining for PCNA, alpha6 integrin subunit, and IL-1RI was found in both the rectal and hepatic tumors. The patients with a rectal GIST may have an increased risk of liver metastasis and a poor prognosis independent of the size of the tumor.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between april 2003 and march 2004].

Tendency of isolated bacteria from infections in abdominal surgery during the period from April 2005 to March 2006 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 384 strains including 18 strains of Candida spp. were isolated from 161 (70.3%) of 229 patients with surgical infections. One hundred and ninty-five strains were isolated from primary infections, and 171 strains were isolated from postoperative infections. From primary infections, aerobic Gram-negative bacteria and aerobic Gram-positive bacteria were predominant, while aerobic Gram-positive bacteria were predominant from postoperative infections. The isolation rate of aerobic Gram-positive bacteria, such as Enterococcus spp. and Staphylococcus aureus were higher from both types of infections. Among anaerobic Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the highest from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Pseudomonas aeruginosa, Klebsiella spp. in this order, and from postoperative infections, E. coli was the most predominantly isolated, followed by Klebsiella pneumoniae and P. aeruginosa. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both primary and postoperative infections. In this series, we noticed no vancomycin-resistant Gram-positive cocci, nor multidrug-resistant P. aeruginosa. But cefazolin-resistant E. coli producing extended spectrum fl-lactamase was seen in 5.0 per cents. We should be carefully followed up the facts that the increasing isolation rates of B. fragilis group and Bilophila wadsworthia which were resistant to both penicillins and cephems.

Successful paclitaxel-based chemotherapy for an alpha-fetoprotein-producing gastric cancer patient with multiple liver metastases.

BACKGROUND: Alpha-fetoprotein (AFP)-producing gastric cancer is known to frequently cause multiple liver metastases and to have an extremely poor prognosis. CASE PRESENTATION: A 64-year-old Japanese man admitted to our hospital was diagnosed with gastric cancer with liver metastases. He underwent a total gastrectomy with splenectomy, and pathological stage IV disease according to the classification proposed by the Japanese Gastric Cancer Association was assigned. The histological diagnosis was poorly differentiated adenocarcinoma, and tumor production of AFP was confirmed by immunohistochemical staining. Following surgery, the patient received combination chemotherapy consisting of TS-1 and paclitaxel. Initially, AFP levels decreased dramatically and computed tomography (CT) revealed regression of liver metastases. However, multiple new liver metastases appeared and serum AFP levels increased after 5 months. A regimen of 5-FU plus paclitaxel followed by paclitaxel monotherapy was used next. Serum AFP levels once again decreased and CT showed regression or disappearance of liver metastases. The patient currently has a very good quality of life, and is receiving weekly paclitaxel monotherapy as an outpatient. No progression of liver metastases has been observed to date. CONCLUSION: We consider this rare case to have significant value with respect to treatment of AFP-producing gastric cancer with multiple liver metastases, and propose that combining surgery with chemotherapeutic agents such as paclitaxel may lead to a better prognosis in such cases.

Laparoscopic surgery for diagnosis and treatment of bowel obstruction: case report of paracecal hernia.

BACKGROUND: Small bowel obstruction cased by paracecal hernia is rare, and the condition is difficult to diagnose preoperatively. We herein report a case of paracecal hernia that was successfully diagnosed and treated with laparoscopic surgery. CASE REPORT: A 74-year-old man admitted our hospital. His previous medical history included appendectomy and diabetes. He had abdominal distension with slight tenderness. Abdominal image examinations gave the appearance of a small bowel obstruction. An emergency operation was performed due to the fear of strangulation. We diagnosed the paracecal hernia with laparoscopy and treated it with a mini-laparotomy. After the operation he was discharged without complications. Using the laparoscopic technique we were able to undergo a minimally invasive treatment, and the patient continues to do well. CONCLUSIONS: This case suggests that the laparoscopic technique is useful for diagnosing and treatment of bowel obstructions.

Laparoscopic management of small bowel incarceration caused by a broad ligament defect: report of a case.

We report the case of a 94-year-old woman who presented with signs of a small bowel obstruction many years after an appendectomy. Abdominal computed tomography (CT) scan showed discontinuity of the small bowel at a point next to the uterus. We made a provisional diagnosis of an internal hernia through a defect in the broad ligament and performed laparoscopic exploration, which revealed a viable ileal loop incarcerated through the broad ligament. Thus, CT scan may be useful for diagnosing this type of defect preoperatively, whereby open surgery can be avoided.

Stem cell factor/c-kit receptor signaling enhances the proliferation and invasion of colorectal cancer cells through the PI3K/Akt pathway.

In this study, we examined the role of c-kit receptor (KIT) signal transduction on the proliferation and invasion of colorectal cancer cells. We found that c-kit was expressed in 2 colorectal cancer cell lines as determined by RT-PCR, Western blot, and flow cytometry. In KIT-positive lines, KIT was activated by stem cell factor (SCF). SCF enhanced cellular proliferation of positive lines as demonstrated by the WST-1 proliferation assay. Furthermore, SCF enhanced the invasive ability of KIT-positive cell lines. SCF stimulation upregulated p44/42 mitogen-activated protein kinase (MAPK) and Akt as shown by Western blot. We examined the roles played by p44/42 MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt pathways in proliferation and invasion. PI3K/Akt activity strongly correlated with proliferation and invasion and p44/42 MAPK was correlated with only invasion. In conclusion, the SCF-enhanced proliferation and invasion of KIT-positive colorectal cancer cells is achieved mainly through the PI3K/Akt pathway.

Vascular endothelial growth factor-C secreted by pancreatic cancer cell line promotes lymphatic endothelial cell migration in an in vitro model of tumor lymphangiogenesis.

OBJECTIVES: To investigate mechanisms underlying lymphatic node metastasis in pancreatic cancer, we examined roles of vascular endothelial growth factor-C (VEGF-C) in tumor lymphangiogenesis. METHODS: We measured VEGF-C secretion by pancreatic cancer cell lines using enzyme-linked immunosorbent assay and examined effects of different cell lines on lymphatic endothelial cells (LECs) in vitro. RESULTS: We identified VEGF-C high-secretion (MIA PaCa-2) and low-secretion cell lines (BxPC-3). The trend of enhancement of LEC proliferation by recombinant human VEGF-C (rVEGF-C) was not statistically significant. Numbers of migrating cells were increased by rVEGF-C treatment in a dose-dependent manner. The MIA PaCa-2 cell culture supernatant caused greater LEC migration than the BxPC-3 supernatant. The VEGF-C effects were significantly inhibited by rVEGF receptor 3 (rVEGF R3)/Fc chimera. In LEC/fibroblast coculture on collagen gel, LEC capillary formation was significantly enhanced by coculture with MIA PaCa-2 cells compared with BxPC-3 cells. Enhanced capillary formation with MIA PaCa-2 cells was inhibited by rVEGF R3/Fc chimera, implying VEGF-C involvement in progression of LEC sprouting in a tumor microenvironment. CONCLUSIONS: Because VEGF-C secreted by pancreatic cancer cells plays an important role in LEC migration in pancreatic cancer lymphangiogenesis, it is possible that rVEGF R3/Fc chimera might have a role in controlling lymph node metastasis.

Synthetic serine protease inhibitor, gabexate mesilate, prevents nuclear factor-kappaB activation and increases TNF-alpha-mediated apoptosis in human pancreatic cancer cells.

Gabexate mesilate (GM), a synthetic serine protease inhibitor, suppresses nuclear factor-kappaB (NF-kappaB) activity in human monocytes or human umbilical vein endothelial cells (HUVECs). In this study we examine whether GM also suppresses NF-kappaB activation and induces apoptosis in human pancreatic cancer cell lines. The addition of tumor necrosis factor alpha (TNF-alpha) did not change the rates of growth of BxPC-3 and MIA PaCa-2. However, in the presence of GM and TNF-alpha, proliferation decreased in a dose-dependent manner. GM- and TNF-alpha-treated cells exhibited morphologic changes indicative of apoptosis, including chromatin condensation and nuclear fragmentation. The NF-kappaB activity of both cell lines was increased by the addition of TNF-alpha, while TNF-alpha-induced NF-kappaB activity was suppressed by prestimulation with GM in a dose-dependent manner. Caspase 3 and 7 activity was significantly increased by TNF-alpha with GM stimulation. Furthermore, GM also suppressed the invasive potential of both cell lines. These results indicate that GM inhibits TNF-alpha-induced NF-kappaB activation and enhances apoptosis in human pancreatic cancer cell lines.

Expression of alpha6 integrin subunit is associated with malignancy in gastric gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common non-epithelial neoplasms of the gastrointestinal tract. The aim of this study was to investigate the clinicopathological and immunohistochemical features of gastric GISTs and to evaluate the degree of integrin expression in order to determine the need for surgery or predict the prognosis for GIST patients. MATERIAL/METHODS: Clinicopathological findings were obtained from patients' records. Specimens from 32 cases of gastric GIST were analyzed with immunohistochemical methods. The c-kit negative examples among the original 48 patients with gastric submucosal and muscle layer tumors were excluded from the study. RESULTS: There was a significant correlation between p53 protein expression and tumor malignancy. The positive staining for proliferating cell nuclear antigen was observed in all patients, and the mean tumor proliferation index for benign and malignant groups were 3.0% and 16.3%, respectively. alpha5beta1 integrin and alpha6 integrin subunit were expressed from moderately to strongly in tumor cells, and alpha 6 integrin subunit expression correlated significantly with whether tumors were classified as benign or malignant. However, there were no significant differences between the survival of GIST patients and integrin expression, mitotic rate, tumor size, or tumor malignancy. CONCLUSIONS: Malignant GISTs show significant expression of alpha6 integrin subunit. It may be useful in supporting other parameters, such as p53, MI, and tumor size. We suggest that alpha6 integrin subunit expression may be useful as an indication for surgery and also as one of several prognostic factors.

Effects of Helicobacter pylori infection on human pancreatic cancer cell line.

BACKGROUND/AIMS: Helicobacter species has been shown to be commonly present in extragastric human organs by polymerase chain reaction (PCR). To date, a few studies have reported that infection by Helicobacter pylori (H. pylori) was a risk factor for pancreatic malignancies, but this was not investigated very well. Therefore, we examined effects of H. pylori infection on human pancreatic cancer cells. METHODOLOGY: Interleukin (IL)-8 and vascular endothelial growth factor (VEGF) secretions by human pancreatic cancer cells which were co-cultured with H. pylori, were measured by enzyme-linked immunosorbent assay (ELISA). We then examined whether activities of proliferation factors nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), and serum response element (SRE) of human pancreatic cancer cells were increased by H. pylori infection. Furthermore, we examined cytotoxin-associated gene A protein (CagA) secretion into pancreatic cancer cells using Western blotting. RESULTS: IL-8 and VEGF secretion levels and activities of proliferation factors NF-kappaB, AP-1, and SRE of human pancreatic cells increased by H. pylori infection. Moreover, CagA secretion into pancreatic cancer cells was confirmed by Western blotting. CONCLUSIONS: Helicobacter pylori infection of human pancreatic cells may increase malignant potential of pancreatic cells, which seems to involve the same mechanisms as in gastric cancer cells.

Clinicopathologic study of intraductal papillary-mucinous tumors and mucinous cystic tumors of the pancreas.

BACKGROUND/AIMS: We analyzed clinicopathologic and imaging findings of intraductal papillary-mucinous tumors (IPMTs) and mucinous cystic tumors (MCTs) of the pancreas to evaluate the difference between IPMTs and MCTs, and to identify the signs indicative of malignancy in IPMTs. METHODOLOGY: Clinicopathological features of 20 patients with IPMT and six patients with MCT of the pancreas were studied. RESULTS: The patients with IPMT comprised 16 males and four females with a mean age of 62.9 years. Eighty percent of IPMTs were located in the pancreatic head, and the mean tumor size was 38.6mm. Recurrence was observed in one patient, who died of IPM adenocarcinoma. In contrast, all patients with MCT were females, with a mean age of 53.0 years. None of the MCTs arose in the pancreatic head, and the mean tumor size was 42.7mm. One patient died of MC adenocarcinoma, but all of the others survived without recurrence. The difference in gender, location of the tumor, and connection to the pancreatic duct reached statistical significance between IPMTs and MCTs. A significant connection to the pancreatic duct and high level of serum carbohydrate antigen 19-9 (CA19-9) was observed in the adenocarcinoma and moderate dysplasia groups of IPMT. CONCLUSIONS: The main duct type and an elevation of serum CA19-9 level suggested malignancy in IPMTs.

The stem cell factor/c-kit receptor pathway enhances proliferation and invasion of pancreatic cancer cells.

BACKGROUND: The transmembrane protein c-kit is a receptor tyrosine kinase (KIT) and KIT is expressed in solid tumors and hematological malignancies such as gastrointestinal stromal tumor (GIST), small-cell lung cancer and chronic myelogenous leukemia (CML). KIT plays a critical role in cell proliferation and differentiation and represents a logical therapeutic target in GIST and CML. In pancreatic cancer, c-kit expression has been observed by immunohistochemical techniques. In this study, we examined the influence of c-kit expression on proliferation and invasion using five pancreatic cancer cell lines. In addition, the inhibitory effect of imatinib mesylate on stem cell factor (SCF)-induced proliferation and invasion was evaluated. Finally, we also analyzed KIT and SCF expression in pancreatic cancer tissues using immunohistochemistry and correlated the results with clinical features. RESULTS: RT-PCR revealed that two pancreatic cancer cell lines, PANC-1 and SW1990, expressed c-kit mRNA. By Western blot analysis, c-kit protein was also present in those lines. In KIT-positive pancreatic cancer cell lines, proliferation and invasion were significantly enhanced by addition of SCF. In contrast, SCF did not enhance proliferation and invasion in the three KIT-negative lines (BxPC-3, Capan-2 and MIA PaCa-2). 5 muM imatinib mesylate significantly inhibited SCF-enhanced proliferation to the same extent compared with the control. Similarly, SCF-enhanced invasive ability was significantly inhibited by 5 muM imatinib mesylate. KIT was expressed in 16 of 42 clinical specimens by immunohistochemistry, and KIT expression was significantly related to venous system invasion. Furthermore, patients expressing both KIT and SCF had a somewhat lower survival. CONCLUSION: Our results demonstrated that the SCF-KIT pathway enhanced the proliferation and invasiveness in KIT-positive pancreatic cancer cell lines and that the enhanced proliferation and invasion were inhibited by imatinib mesylate. We propose that inhibitors of c-kit tyrosine kinase receptor have the potential to slow the progression of KIT-positive pancreatic cancers.