Laparoscopic surgery for De Garengeot's hernia in a man after inguinal hernia surgery with a mesh plug: a case report and review of literature.

BACKGROUND: De Garengeot's hernia is a rare case of a femoral hernia that contains the appendix. Here we report a case of De Garengeot's hernia that occurred in a male patient who had a history of inguinal hernia surgery using a mesh plug. There were no reports of De Garengeot's hernia with a history of surgery for inguinal hernia, and the surgical question was whether we could successfully treat a patient with minimally invasive laparoscopic surgery using a mesh. CASE PRESENTATION: This case involved 75-year-old man with a history of right indirect inguinal hernia surgery using a mesh plug without on-lay mesh, who presented with a 5-day history of a right groin lump. Abdominal CT revealed an incarcerated appendix within the right femoral hernia and fluid collection around the appendix. Laparoscopic surgery was initiated and the incarcerated appendix was released with traction. There was no contamination around the appendix or the femoral ring, the appendix was removed, and the femoral hernia was repaired using mesh. Laparoscopic surgery was useful in first evaluating the inflammatory status of the appendix. As it was determined that there was little inflammation around the appendix and femoral ring, it was possible to repair the hernia using mesh. CONCLUSIONS: De Garengeot's hernias are rare and there is currently no standardized approach. Even if it is a recurrent hernia in the groin, laparoscopic surgery can be useful for diagnosis and treatment, but the use of mesh requires further careful consideration.

Adenosquamous carcinoma coexisting with intraductal papillary mucinous neoplasm of the pancreas: a case report.

BACKGROUND: Adenosquamous carcinoma of the pancreas is a rare variant, with a worse prognosis than pancreatic ductal adenocarcinoma; moreover, it has characteristic clinical and histopathological features. Studies have mentioned the differentiation of intraductal papillary mucinous neoplasms into mucinous/tubular adenocarcinomas; however, their transdifferentiation into adenosquamous carcinoma remains unclear. CASE PRESENTATION: An 80-year-old Japanese woman was referred to our hospital for further examination of multiple pancreatic cysts. Enhanced computed tomography after close follow-up for 6 years revealed a new nodule with poor enhancement on the pancreatic body. Distal pancreatectomy and splenectomy were performed. Histopathological examination revealed an adenosquamous carcinoma with coexisting intraductal papillary mucinous neoplasms; moreover, the intraductal papillary mucinous neoplasms lacked continuity with the adenosquamous carcinoma. Immunohistochemical analysis revealed squamous cell carcinoma and differentiation from adenocarcinoma to squamous cell carcinoma. Gene mutation analysis revealed KRASG12D and KRASG12R mutations in adenosquamous carcinoma components and intraductal papillary mucinous neoplasm lesions, respectively, with none showing the mutation of GNAS codon 201. The final histopathological diagnosis was adenosquamous carcinoma with coexisting intraductal papillary mucinous neoplasms of the pancreas. CONCLUSIONS: This is the rare case of adenosquamous carcinoma with coexisting intraductal papillary mucinous neoplasms of the pancreas. To investigate the underlying transdifferentiation pathway of intraductal papillary mucinous neoplasms into this rare subtype of pancreatic cancer, we explored gene mutation differences as a clinicopathological parameter.

Clinical Outcomes of Intraoperative Radiotherapy, Postoperative Radiotherapy, and Definitive Radiotherapy for Non-metastatic Pancreatic Cancer.

OBJECTIVE: The aim of this study is to evaluate the utility of adjuvant radiotherapy (intraoperative radiotherapy, IORT; postoperative radiotherapy, PORT), and definitive radiotherapy for non-metastatic pancreatic cancer. METHODS: Ninety-nine patients were analyzed. Thirty patients underwent IORT with surgery, 31 underwent PORT after surgery, and 38 underwent definitive radiotherapy. Tumor stage [Union for International Cancer Control (UICC) 2009] was as follows: Stage I, 7; IIA, 16; IIB, 31; III, 45. The doses for IORT, PORT, and definitive radio therapy were 20 to 30, 40 to 64.6, and 50.4 to 61.2 Gy, respectively. Associations between clinical parameters including age, gender, tumor site, stage, performance status, surgical margin, and use of chemotherapy and local control (LC) or overall survival (OS) were analyzed. RESULTS: Follow-up periods for all patients were 1.1-145 months (median, 11). OS rate in the IORT, PORT, and definitive radiotherapy groups was 22%, 16%, and 6%, respectively, at 2 years. The 5-year OS rate was 13%, 3.2%, and 0%, respectively. Local control rate at 2 years was 33%, 35%, and 0%, respectively. No Grade ≥ 3 tox icities were observed. Distant metastasis was less common in the IORT group. Stage and surgical margin were sig nificant factors for OS after IORT. Performance status and chemotherapy were significant factors for OS after PORT and definitive radiotherapy. CONCLUSIONS: The present study showed the safety of the three treatment modalities, but the outcomes were not satisfactory. More intensive strategies including radiotherapy should be investigated.

Hyperthermia with Chemotherapy for Unresectable Gastric Cancer in a Patient with a Vagus Nerve Stimulator Implant: A Case Report.

BACKGROUND Radiofrequency (RF) hyperthermia is commonly used as an adjunct to established treatment modalities such as chemotherapy and radiotherapy for the management of cancer patients. This case report aims to introduce the use of hyperthermia, in combination with chemotherapy, for the treatment of unresectable gastric cancer in a patient implanted with a vagus nerve stimulator (VNS). CASE REPORT A 55-year-old man with dermatomyositis, laryngeal squamous cell carcinoma in situ and double synchronous gastric cancer was found to have unresectable gastric disease during surgery despite neoadjuvant chemotherapy. Postoperatively, he received chemotherapy with RF hyperthermia. The patient had a VNS implant to treat epileptic seizures. VNS failure due to RF hyperthermia was an area of significant concern, and the procedures were completed with a full preparation to manage epileptic seizures in the event of its anticipated occurrence. Twenty-one thermotherapies were performed over 21 weeks. After 3 courses of S-1 chemotherapy (12 weeks) with RF hyperthermia without any adverse events, the regimen was changed to S-1+ CDDP combination chemotherapy (SP) and RF hyperthermia. The patient continued to receive treatment with a decrease in the size of the primary gastric tumors as well as lymph node metastases, without major adverse events, until he died due to disseminated disease. CONCLUSIONS We report the first case of unresectable gastric cancer with VNS implants in which chemo-hyperthermal therapy was safe and successful. This case report highlights the importance of providing a multidisciplinary treatment with appropriate measures for patients with intractable cancer who have received special treatments for underlying comorbidities.

Efficacy of Hyperthermia in Treatment of Recurrent Metastatic Breast Cancer After Long-Term Chemotherapy: A Report of 2 Cases.

BACKGROUND Breast cancer has a long-term prognosis with various multimodality treatments. This report introduces the effectiveness of radiofrequency (RF) hyperthermia in the long-term treatment for recurrent/metastatic breast cancer. CASE REPORT In the first case, the patient had bone and liver metastases during the course of chemotherapy, hormone therapy, and radiotherapy for 27 years after curative resection of breast cancer. Finally, she received RF hyperthermia alone for liver metastasis and showed a decrease in tumor markers and reduction in liver metastasis on computed tomography (CT). In the second case, the patient underwent curative resection for multiple occurrences on the left side of the breast. She received postoperative chemotherapy combined with hormone therapy but had metachronous local recurrences. She continued hormone therapy after 2 local recurrence resections; unfortunately, she had bone, liver, and lung metastases and pleural dissemination. Eventually, the patient received RF hyperthermia combined with oral chemotherapy. Her tumor markers decreased, and CT showed disappearance of lung metastasis and improved pleural dissemination. Furthermore, the reduction of chemotherapy adverse events due to hyperthermia allowed the patient to continue chemotherapy and improved her quality of life. CONCLUSIONS We present 2 cases in which RF hyperthermia had a positive effect despite the presence of a recurrent tumor after various types of surgery, chemotherapy, and radiotherapy. This report suggests that the addition of RF hyperthermia to conventional multidisciplinary therapies may enhance the therapeutic effect of these treatments and improve the quality of life in patients with recurrent breast cancer.

Invasive Ductal Carcinoma Arising in Mucinous Cystic Neoplasm of Pancreas: A Case Report.

BACKGROUND Mucinous cystic neoplasm (MCN) of the pancreas is a rare mucin-producing cystic neoplasm that has a characteristic histological feature referred to as ovarian-type stroma (OS) underlying the epithelium. Pancreatic ductal carcinoma arises from MCN as a precursor lesion, but data on progression pathways are limited. CASE REPORT A 40-year-old female was referred to our hospital for further investigation of a pancreatic cyst. Further examination showed a 7.0 cm multilocular cyst in the pancreatic tail and a solid mass in the thick septum of the cystic tumor. Distal pancreatectomy and splenectomy were performed. Histological examination revealed a moderately differentiated invasive ductal carcinoma (IDC) with a diameter of 0.5 cm in the thick septum of the cystic lesion and a cyst wall composed of epithelium with low-grade to severe dysplasia. The epithelium covered an OS. Pathological diagnosis was IDC arising in MCN of the pancreas. Immunohistochemical examination showed that MUC1 expression was negative in MCN but positive in IDC. KRAS mutation was observed in both MCN and IDC regions. CONCLUSIONS We present a rare case of moderately differentiated pancreatic IDC arising in MCN. To elucidate the underlying progression pathway, we explored the correlation between KRAS mutation and MUC expression as a clinicopathological parameter.

Solid variant of serous cystadenoma of the pancreas.

We describe a case of a solid variant of serous cystadenoma of the pancreas. The preoperative examination results led to a diagnosis of a nonfunctional pancreatic islet cell tumour, and the patient underwent a pylorus-preserving pancreaticoduodenectomy. The tumour was diagnosed as a solid variant of serous cystadenoma by histopathological examination. Solid variant of serous cystadenoma of the pancreas is difficult to diagnose preoperatively. More cases must be accumulated and investigated to obtain clues for accurate diagnosis.

IGF-1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF-1/PI3K/Akt signaling pathway in pancreatic cancer cells.

BACKGROUND: Type-1 insulin-like growth factor (IGF-1) up-regulates cell proliferation and invasiveness through activation of PI3K/Akt signaling pathway. IGF-1 also down-regulates the tumor suppressor chromosome 10 (PTEN). We investigated the mechanism by which IGF-1 affects cell proliferation and invasion by suppression of PTEN phosphorylation and interaction with PI3K/PTEN/Akt/NF-small ka, CyrillicB signaling pathway in pancreatic cancer. MATERIALS AND METHODS: The expression of IGF-1 receptor (IGF-1R) and PTEN in five pancreatic cancer cell lines was determined by RT-PCR and Western blot. Proliferation and invasion were investigated by WST-1 assay and Matrigel-double chamber assay. Pancreatic cancer cells were transfected with PTEN siRNA to investigate which signaling pathway correlates in regulation of cancer cell proliferation and invasion. RESULTS: Five pancreatic cancer cell lines expressed PTEN and IGF-1R in mRNA and protein levels. Suppression of PTEN phosphorylation strongly enhanced cell proliferation and invasion stimulated with IGF-1 via activation of PI3K/Akt/NF-small ka, CyrillicB signaling pathway. In addition, knockdown of PTEN by siRNA transfection also enhanced activation of PI3K/Akt/NF-small ka, CyrillicB pathway, subsequently up-regulating cell invasiveness and proliferation. CONCLUSIONS: The IGF-1/PI3K/PTEN/Akt/NF-small ka, CyrillicB cascade may be a key pathway stimulating metastasis of pancreatic cancer cells. We suggest that interfering with the functions of IGF-1/PI3K/Akt/NF-small ka, CyrillicB might be a novel therapeutic approach to inhibit aggressive spread of pancreatic cancer.

Proteasome inhibitor MG132 inhibits angiogenesis in pancreatic cancer by blocking NF-kappaB activity.

Since angiogenesis enables solid tumors, including pancreatic cancer (PaCa), to grow and metastasize, the development of anti-angiogenic agents is currently one of the urgent issues. Proteasome inhibitors are well known for inhibiting nuclear factor-kappa B (NF-kappaB) activity in various cancer cells, but little is known about their biologic mechanisms against angiogenesis in PaCa. We divided human PaCa cell lines into high-angiogenic (BxPC-3 and SW 1990) and low-angiogenic (MIA PaCa-2 and Capan-2) groups. The high-angiogenic PaCa cell lines constitutively expressed high NF-kappaB activity and produced high levels of vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8). The conditioned media from BxPC-3 significantly enhanced both proliferation of and tube formation by human umbilical vein endothelial cells (HUVECs) and these enhancements were significantly inhibited by the proteasome inhibitor MG132 treatment. Collectively, MG132 blocked PaCa-derived VEGF and IL-8 production through inhibition of NF-kappaB activity. Thus, proteasome inhibitors may prove beneficial as anti-angiogenic therapy for PaCa. Our studies show that MG132, a proteasome inhibitor, significantly blocked pancreatic-cancer-associated angiogenesis through inhibition of NF-kappaB and NF-kappaB-dependent proangiogenic gene products VEGF and IL-8.

PTEN regulates angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells.

Phosphoinositide 3-kinase (PI3K) pathway exerts its effects through Akt, its downstream target molecule, and thereby regulates various cell functions including cell proliferation, cell transformation, apoptosis, tumor growth, and angiogenesis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has been implicated in regulating cell survival signaling through the PI3K/Akt pathway. However, the mechanism by PI3K/PTEN signaling regulates angiogenesis and tumor growth in vivo remains to be elucidated. Vascular endothelial growth factor (VEGF) plays a pivotal role in tumor angiogenesis. The effect of PTEN on VEGF-mediated signal in pancreatic cancer is unknown. This study aimed to determine the effect of PTEN on both the expression of VEGF and angiogenesis. Toward that end, we used the siRNA knockdown method to specifically define the role of PTEN in the expression of VEGF and angiogenesis. We found that siRNA-mediated inhibition of PTEN gene expression in pancreatic cancer cells increase their VEGF secretion, up-modulated the proliferation, and migration of co-cultured vascular endothelial cell and enhanced tubule formation by HUVEC. In addition, PTEN modulated VEGF-mediated signaling and affected tumor angiogenesis through PI3K/Akt/VEGF/eNOS pathway.

Middle-colic artery aneurysm associated with segmental arterial mediolysis, successfully managed by transcatheter arterial embolization: report of a case.

An aneurysm of the middle-colic artery, associated with segmental arterial mediolysis (SAM), is a rare condition. This report describes a case of a middle-colic artery aneurysm that was associated with SAM. A 57-year-old man was admitted to our hospital because of severe abdominal pain. A rupture of a middle-colic artery aneurysm was diagnosed by computed tomography, and angiography showed that it may have been associated with SAM. The ruptured aneurysm was successfully treated with transcatheter arterial embolization. Transcatheter arterial embolization might be one of the best treatments for such a complicated aneurysm occurring in a visceral artery.

IL-1alpha secreted by colon cancer cells enhances angiogenesis: the relationship between IL-1alpha release and tumor cells' potential for liver metastasis.

BACKGROUND AND OBJECTIVES: Interleukin (IL)-1alpha plays an important role in colon cancer progression and angiogenesis. We here asked whether IL-1alpha derived from cancer cells modulates vascular endothelial cell growth, migration and tubule formation. METHODS: The existence of IL-1alpha mRNA and protein in colon cancer cell lines (WiDr, HT-29, Caco-2, COLO 320) were investigated with RT-PCR and ELISA. Proliferation and invasion were investigated by MTS assay and Matrigel-double chamber assay. To answer our main question, we performed angiogenesis assay used an in vitro model consisting of co-cultivated tumor cells and stromal cells. RESULTS: IL-1alpha mRNA and protein were detected in highly metastatic colon cancer cells (WiDr and HT-29). Recombinant IL-1alpha significantly enhanced growth and invasiveness of human umbilical vein endothelial cells (HUVEC) (P < 0.01). Moreover, HUVEC growth and migration were significantly enhanced by WiDr compared to control (without co-culture) or Caco-2 (P < 0.05). Exogenous rIL-1alpha significantly enhanced HUVEC tube-like formation in a dose-dependent manner (P < 0.01) in a HUVEC/fibroblast co-cultivation system. Moreover, WiDr significantly enhanced HUVEC tubule formation compared with control or Caco-2 (P < 0.01). CONCLUSION: Based on these findings, we conclude that colon cancer cell-derived IL-1alpha up-regulates angiogenesis by modulating stromal cells within the tumor cells' microenvironment.

Interleukin-1alpha secreted by pancreatic cancer cells promotes angiogenesis and its therapeutic implications.

BACKGROUND: Previously we reported the critical role of interleukin (IL)-1alpha in liver metastasis from pancreatic cancer (PaCa). However, its role in angiogenesis and metastasis, particularly as it relates to the interaction between tumor and stromal cells, was not clearly elucidated. To further investigate, we initially compared vascular endothelial cell migration and tube formation in human PaCa cell lines that differed in metastatic potential. We then compared the effects of IL-1alpha derived from PaCa cells on the same processes. MATERIALS AND METHODS: Expression of IL-1alpha mRNA and protein in PaCa cells was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. IL-1alpha mRNA and protein were detected only in predominantly liver-metastatic PaCa cells. Next, we examined differences in migration and tube formation by human umbilical vein endothelial cells (HUVECs) in the various PaCa cells using invasion and angiogenesis assays, respectively. Furthermore, we determined the effects of IL-1alpha secreted by PaCa cells on migration and tube formation by HUVECs using coculture experiments. RESULTS: Expression of IL-1alpha mRNA and protein was observed only by the highly liver-metastatic PaCa cell lines BxPC-3 and SW 1990. Both HUVEC migration and tube formation were significantly enhanced by coculture with metastatic PaCa cells and IL-1alpha (P < 0.01). Similarly, blockade of IL-1alpha by its antagonist inhibited HUVEC migration and tube formation (P < 0.01). CONCLUSIONS: Our results indicate that IL-1alpha secreted by PaCa cells plays an important role in metastasis through vascular endothelial cell invasion and angiogenesis. Thus, blocking IL-1alpha is a potential novel therapeutic strategy in PaCa.

CXCL8/IL-8 and CXCL12/SDF-1alpha co-operatively promote invasiveness and angiogenesis in pancreatic cancer.

CXC-chemokines are involved in the chemotaxis of neutrophils, lymphocytes and monocytes. However, role of these chemokines in tumorigenesis, especially with regard to interaction between tumor and its microenvironment, has not been clearly elucidated. The purpose of this study was to analyze the co-operative role of CXCL8 and CXCL12 in the tumor-stromal interaction in pancreatic cancer (PaCa). Using enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR), we initially confirmed the expression of ligands and receptors, respectively, of CXC-chemokines in PaCa and stromal cells. We examined the co-operative role of CXCL8 and CXCL12 in proliferation/invasion of PaCa and human umbilical vein endothelial cells (HUVECs), and in HUVEC tube-formations through tumor-stromal interaction by MTS, Matrigel invasion, and angiogenesis assays, respectively. We detected expression of CXCR4, but not CXCR2, in all PaCa cells and fibroblasts. PaCa cells secreted CXCL8, and fibroblast cells secreted CXCL12. CXCL8 production in PaCa was significantly enhanced by CXCL12, and CXCL12 production in fibroblasts was significantly enhanced by co-culturing with PaCa. CXCL8 enhanced proliferation/invasion of HUVECs but did not promote proliferation/invasion of PaCa. Both recombinant and PaCa-derived CXCL8 enhanced tube formation of HUVECs that were co-cultured with fibroblast cells. CXCL12 enhanced the proliferation/invasion of HUVECs and the invasion of PaCa cells but had no effect on tube formation of HUVEC. We showed that PaCa-derived CXCL8 and fibroblast-derived CXCL12 cooperatively induced angiogenesis in vitro by promoting HUVEC proliferation, invasion, and tube formation. Thus, corresponding receptors CXCR2 and CXCR4 are potential antiangiogenic and antimetastatic therapeutic targets in PaCa.

Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival.

BACKGROUND: The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. To evaluate the correlation between PTEN expression and clinicopathological characteristics of colorectal cancer patients with and without liver metastases, we investigated PTEN expression in primary colorectal cancer and colorectal cancer liver metastases. METHODS: Sixty-nine pairs of primary colorectal cancer and corresponding liver metastasis specimens were analyzed immunohistochemically, and the correlation between immunohistochemical findings and clinicopathological factors was investigated. Seventy primary colorectal cancer specimens from patients without liver metastases were used as controls. RESULTS: PTEN was strongly expressed in 44 (62.9%) colorectal cancer specimens from patients without liver metastases. In contrast, PTEN was weakly expressed in 52 (75.4%) primary colorectal cancer specimens from patients with liver metastases, and was absent in liver metastases. Weak PTEN expression in colorectal cancer tissues was significantly associated with advanced TNM stage (p < 0.01) and lymph node metastasis (p < 0.05). PTEN expression was significantly stronger in primary colorectal cancer specimens from patients without liver metastases. Furthermore, among colorectal cancer patients with liver metastases, the 5-year survival rate was significantly higher in patients with positive PTEN expression compared to those with negative PTEN expression (p = 0.012). CONCLUSION: Our results suggest that loss of PTEN expression is involved with colorectal cancer aggressive capacity and that diagnostic evaluation of PTEN expression may provide valuable prognostic information to aid treatment strategies for colorectal cancer patients.

Granulocyte-colony stimulating factor producing rectal cancer.

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF)-producing cancer has been reported to occur in various organs, especially the lung. However, G-CSF-producing colorectal cancer (CRC) has never been reported in the English literature. CASE PRESENTATION: A 57-year-old man was admitted for the surgical removal of a rectal cancer. Some hepatic tumors in the liver were revealed concurrently, and their appearance suggested multiple liver metastases. Low anterior resection was performed. with the help of histopathological examination and immunohistochemical studies, we diagnosed this case to be an undifferentiated carcinoma of the rectum. After the operation, the white blood cell (WBC) count increased gradually to 81,000 cells/microL. Modified-FOLFOX6 therapy was initiated to treat the liver metastases, but there was no effect, and peritoneal dissemination had also occurred. The serum level of G-CSF was elevated to 840 pg/mL (normal range, <18.1 pg/mL). Furthermore, immunohistochemistry with a specific monoclonal antibody against G-CSF was positive; therefore, we diagnosed this tumor as a G-CSF-producing cancer. The patient died from rapid growth of the liver metastases and peritoneal dissemination 2 months after surgery. CONCLUSION: This is the first case of G-CSF-producing rectal cancer, and its prognosis was very poor.

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.

Opposing effects of n-6 and n-3 polyunsaturated fatty acids on pancreatic cancer growth.

OBJECTIVES: Epidemiologic studies suggest that fish oil, rich in n-3 polyunsaturated fatty acids (PUFA), possesses antitumor activity, whereas n-6 PUFAs may stimulate the development of cancers. The aim of this study was to evaluate the effects of n-6 and n-3 PUFAs on the growth of pancreatic cancer. METHODS: The n-6 PUFA arachidonic acid (AA) stimulated the growth of cyclooxygenase (COX) 2 positive human pancreatic cancer (PaCa) cells, which was mediated by COX-2 generated prostaglandin E2 (PGE2) binding to EP2 and EP4 receptors. In contrast, the n-3 PUFA eicosapentaenoic acid decreased the growth of COX-2-positive and COX-2-negative PaCa cells. The COX-2-dependent mechanism of eicosapentaenoic acid was mediated by binding of PGE3 to EP2 and EP4 receptors. Dietary intake of n-3 PUFAs decreased the growth of pancreatic cancers in a xenograft model, which was accompanied by a decrease of PGE2 and an increase of PGE3 in the tumors. CONCLUSIONS: Our studies provide evidence that n-3 PUFAs possess antitumor activities, whereas n-6 PUFAs stimulate pancreatic tumor growth. The opposite effects of n-3 and n-6 PUFAs are mediated by the formation of different prostaglandin species. n-3 PUFAs may prove beneficial as monotherapy or combination therapy with standard chemotherapeutic agents in pancreatic cancer patients.

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.