Yefei Rong

Connective tissue growth factor enhances the migration of gastric cancer through downregulation of E-cadherin via the NF-κB pathway.

Local invasion and distant metastasis are difficult problems for surgical intervention and treatment in gastric cancer. Connective tissue growth factor (CTGF/CCN2) was considered to have an important role in this process. In this study, we demonstrated that expression of CTGF was significantly upregulated in clinical tissue samples of gastric carcinoma (GC) samples. Forced expression of CTGF in AGS GC cells promoted their migration in culture and significantly increased tumor metastasis in nude mice, whereas RNA interference‐mediated knockdown of CTGF in GC cells significantly inhibited cell migration in vitro. We disclose that CTGF downregulated the expression of E‐cadherin through activation of the nuclear factor‐κappa B (NF‐κB) pathway. The effects of CTGF in GC cells were abolished by dominant negative IκappaB. Collectively, these data reported here demonstrate CTGF could modulate the NF‐κappaB pathway and perhaps be a promising therapeutic target for gastric cancer invasion and metastasis. (Cancer Sci 2011; 102: 104–110)

Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine

BackgroundPancreatic cancer is a common, highly lethal disease with a rising incidence. MUC1 is a tumor-associated antigen that is over-expressed in pancreatic adenocarcinoma. Active immunotherapy that targets MUC1 could have great treatment value. Here we investigated the preventive and therapeutic effect of a MUC1 DNA vaccine on the pancreatic cancer.MethodsMUC1-various tandem repeat units(VNTR) DNA vaccine was produced by cloning one repeat of VNTR and inserting the cloned gene into the pcDNA3.1. In the preventive group, female C57BL/6 mice were immunized with the vaccine, pcDNA3.1 or PBS; and challenged with panc02-MUC1 or panc02 cell. In the therapeutic group the mice were challenged with panc02-MUC1 or panc02 cell, and then immunized with the vaccine, pcDNA3.1 or PBS. The tumor size and the survival time of the animals were compared between these groups.ResultsThe DNA vaccine pcDNA3.1-VNTR could raise cytotoxic T lymphocyte (CTL) activity specific for MUC1. In the preventive experiment, the mice survival time was significantly longer in the vaccine group than in the control groups (P < 0.05). In the therapeutic experiment, the DNA vaccine prolonged the survival time of the panc02-MUC1-bearing mice (P < 0.05). In both the preventive and therapeutic experiments, the tumor size was significantly less in the vaccine group than in the control groups (P < 0.05). This pcDNA3.1-VNTR vaccine, however, could not prevent the mice attacked by panc02 cells and had no therapeutic effect on the mice attacked by panc02 cells.ConclusionThe MUC1 DNA vaccine pcDNA3.1-VNTR could induce a significant MUC1-specific CTL response; and had both prophylactic and therapeutic effect on panc02-MUC1 tumors. This vaccine might be used as a new adjuvant strategy against pancreatic cancer.

IRF-2 is over-expressed in pancreatic cancer and promotes the growth of pancreatic cancer cells

Pancreatic cancer is one of the most malignant diseases in the world. Interferon regulator factor 2 (IRF-2), an interferon regulatory factor, has been known to act as an oncogene in distinct types of cancer. In this study, we found that the expression of IRF-2 was up-regulated in primary pancreatic cancer samples and associated with tumor size, differentiation, tumor–node–metastasis stage, and survival of the patients. In pancreatic cancer cells, knockdown on the expression of IRF-2 inhibited cell growth in the liquid culture and on the soft agar. Mechanistically, IRF-2 modulated the growth of pancreatic cancer cells through regulating proliferation and apoptosis effectors, such as cyclin D1 and BAX. Collectively, these results suggest that IRF-2 plays an important role in the tumorigenesis of pancreatic cancer and down-regulation of IRF-2 would be a new treatment target for pancreatic cancer.

Granulocytic sarcoma of the pancreas: A case report and review of the literatures

BackgroundGranulocytic sarcoma (GS) is a form of acute myeloid leukemia (AML), also known as extramedullary myeloid tumor or chloroma. It forms a solid malignant tumor consisting of myelocytes or granulocytes and is typically located in bone while occurrence in other parts of the body is rare.Case presentationWe reported a 40-year-old male patient who had jaundice, highly elevated bilirubin, and a mass highly suspicious of pancreatic head carcinoma. We performed surgery and the pathology and immunohistochemistry suggested GS; however the blood test and the bone marrow infiltration showed no evidence of AML. In our review of the published reports of GS, we only found six reports of the GS in the pancreas, and we suggested that immunohistochemical staining should be used to accurately differentiate GS from other pancreatic cancer and other types of leukemia.ConclusionsThe accurate diagnosis of GS is necessary for determining prognosis and deciding appropriate therapy.

Downstream Carcinogenesis Signaling Pathways by Green Tea Polyphenols: A Translational Perspective of Chemoprevention and Treatment for Cancers

Green tea is one of the most popular beverages around the world. For several decades, numerous epidemiological, preclinical and clinical studies have demonstrated that green tea polyphenols (GTPs), especially epigallocatechin-3-gallate (EGCG) have cancer-preventing effects on various cancers. In this review, we present inhibition of carcinogenesis in different animal models by GTPs or EGCG, including prostate cancer, bladder cancer, breast cancer, intestinal cancer, colon cancer, gastric cancer, lung cancer, oral cancer and skin cancer. In vitro studies showed that GTPs/EGCG potently induces apoptosis, cell cycle arrest and suppresses metastasis in tumor cells but not in their normal cell counterparts. The molecular mechanisms of these activities are discussed in detail to elucidate GTPs/EGCG downstream carcinogenesis signaling pathways and their values of perspective of chemoprevention and treatment for cancers.

Primary small cell carcinoma of the pancreas: rare type of pancreatic cancer and review of the literatures.

Back groundPrimary small cell carcinoma of the pancreas (SCCP) is a rare malignancy with an extremely poor prognosis which accounts for 1 to 1.4 percent of all pancreatic malignancies.Case presentationWe present the case of a 62-year-old man with a half-month history of upper abdominal discomfort who was diagnosed with SCC of the pancreatic tail. A Chest X-ray showed no evidence of primary lung tumor. The diagnosis of a SCCP was confirmed by post-surgery pathology and immunohistology. In our review of the published reports of SCCP, we only found a few cases reported in the literatures. The diagnosis of SCCP needs the post-surgery pathology and immunohistology and the prognosis of SCCP is extremely poor. There was a significant increase in median survival, from 1 to 6 months, in treated patients compared to patients treated only by symptomatic management. Chemotherapy was the most common treatment and the combination of cisplatin/etoposide was most frequently prescribed.ConclusionThe accurate diagnosis of (SCCP) is necessary for determining prognosis and deciding appropriate therapy.

TRAF6 is over-expressed in pancreatic cancer and promotes the tumorigenicity of pancreatic cancer cells.

Pancreatic cancer is one of the most lethal malignancies, with a poor response to chemotherapy and therefore it is important to identify novel therapeutic targets. TNF receptor-associated factor 6 (TRAF6) , a regulator of NF-κB signaling, has been found recently to be involved in tumorigenesis. However, its function in pancreatic cancer remains poorly understood. Here, we found that the expression of TRAF6 was up-regulated in pancreatic cancer tissues. Moreover, over-expression of TRAF6 in pancreatic cancer cells promoted cell proliferation and migration, whereas down-regulation of TRAF6 impaired the tumorigenicity of pancreatic cancer cells in vitro and in vivo. Mechanistically, TRAF6 regulated the expression of multiple genes involved in cell growth, apoptosis and migration. Our results suggested several important roles of TRAF6 in the pathogenesis of pancreatic cancer. TRAF6 might therefore represent a potential therapeutic target.

Pancreatic tuberculosis with splenic tuberculosis mimicking advanced pancreatic cancer with splenic metastasizes: a case report

A 60-year-old woman presented with vague abdominal pain for one week was referred to pancreatic tail carcinoma accompanied with splenic metastasizes. She came to our hospital for further treatment. Ultrasonography and abdominal computed tomography (CT) revealed a pancreatic tail tumor with splenic metastasizes. There was no history of tuberculosis. Laparotomy was performed because pancreatic tail carcinoma with splenic metastasizes was highly suspected. Indurated mass in the pancreatic tail and sporadic metastasizes in the spleen had been found during the surgery. The pancreatic tail and the spleen were removed and proved to be tuberculosis on histological examination of a frozen section. The patient was given antituberculosis therapy and is now getting well. Tuberculosis should be considered in the differential diagnosis of pancreatic masses. The response to antituberculosis treatment is very favorable.

Cilia loss sensitizes cells to transformation by activating the mevalonate pathway

Although cilia loss and cell transformation are frequently observed in the early stage of tumorigenesis, the roles of cilia in cell transformation are unknown. In this study, disrupted ciliogenesis was observed in cancer cells and pancreatic cancer tissues, which facilitated oncogene-induced transformation of normal pancreatic cells (HPDE6C7) and NIH3T3 cells through activating the mevalonate (MVA) pathway. Disruption of ciliogenesis up-regulated MVA enzymes through &bgr; catenin–T cell factor (TCF) signaling, which synchronized with sterol regulatory element binding transcription factor 2 (SREBP2), and the regulation of MVA by &bgr;-catenin–TCF signaling was recapitulated in a mouse model of pancreatic ductal adenocarcinoma (PDAC) and human PDAC samples. Moreover, disruption of ciliogenesis by depleting Tg737 dramatically promoted tumorigenesis in the PDAC mouse model, driven by KrasG12D, which was inhibited by statin, an inhibitor of the MVA pathway. Collectively, this study emphasizes the crucial roles of cilia in governing the early steps of the transformation by activating the MVA pathway, suggesting that statin has therapeutic potential for pancreatic cancer treatment.

SF3B4 is decreased in pancreatic cancer and inhibits the growth and migration of cancer cells

Splicing factor 3b subunit 4, a critical component of pre-message RNA splicing complex, has been reported to play an important part in the tumorigenesis. However, the expression pattern and biological role of splicing factor 3b subunit 4 in pancreatic cancer have never been investigated. In this study, we found that both the messenger RNA (p < 0.001) and protein level of splicing factor 3b subunit 4 were decreased significantly in pancreatic cancer specimens compared with their adjacent normal tissues. Overexpression of splicing factor 3b subunit 4 in pancreatic cancer cells inhibited cell growth and motility in vitro, while suppressing splicing factor 3b subunit 4 expression promoted the proliferation and migration of pancreatic cancer cells. In addition, splicing factor 3b subunit 4 was found to inhibit the activity of signal transducer and activator of transcription 3 signaling via downregulating the phosphorylation of signal transducer and activator of transcription 3 on a tyrosine residue at position 705. Taken together, these findings demonstrated that splicing factor 3b subunit 4 acted as a suppressive role in pancreatic cancer and indicated that restoring the function of splicing factor 3b subunit 4 might be a strategy for cancer therapy.