Mucosa-associated lymphoid tissue lymphoma of the duodenum together with multiple intra-abdominal thromboses and hepatitis C virus infection: a case report

Mucosa associated lymphoid tissue MALT lymphoma is a low grade malignancy that arises most commonly from the gastric mucosa. Small intestinal involvement is very rare. The causative relationship between Helicobacter pylori and the gastric MALT lymphoma is a well known issue, but recently there are several data suggesting the role of hepatitis C virus (HCV) infection in the pathogenesis of lymphoma including MALT lymphoma. Herein we present a rare case of duodenal MALT lymphoma with multiple intra-abdominal thromboses together with HCV infection that was confirmed by real-time polymerase chain reaction detecting HCV-RNA within the peripheral blood mononuclear cells

Role of thrombin receptor in breast cancer invasiveness

Invasion, the ability of an epithelial cancer cell to detach from and move through a basement membrane, is a central process in tumour metastasis. Two components of invasion are proteolysis of extracellular matrix and cellular movement through it. A potential promoter of these two processes is thrombin, the serine proteinase derived from the ubiquitous plasma protein prothrombin. Thrombin promotes the invasion of MDA-MB231 breast tumour cells (a highly aggressive cell line) in an in vitro assay. Invasion by MDA-MB436 and MCF-7 cells, less aggressive cell lines, is not promoted by thrombin. Thrombin, added to the cells, is a stimulator of cellular movement; fibroblast-conditioned medium is the chemotaxin. Thrombin-promoted invasion is inhibited by hirudin. Stimulation of invasion is a receptor-mediated process that is mimicked by a thrombin receptor-activating peptide. Thrombin has no effect on chemotaxis in vitro. Thrombin receptor is detectable on the surface of MDA-MB231 cells, but not on the other two cell lines. Introduction of oestrogen receptors into MDA-MB231 cells by transfection with pHEO had no effect on thrombin receptor expression, in the presence or absence of oestradiol. This paper demonstrates that thrombin increases invasion by the aggressive breast cancer cell line MDA-MB231 by a thrombin receptor-dependent mechanism. © 1999 Cancer Research Campaig

Hyperfibrinogenemia is associated with lymphatic as well as hematogenous metastasis and worse clinical outcome in T2 gastric cancer

BACKGROUND: Abnormal hemostasis in cancer patients has previously been described, however the correlation between the plasma fibrinogen level and cancer metastasis and prognosis has not been reported in a large-scale clinical study. METHODS: Preoperative plasma fibrinogen levels were retrospectively examined in 405 patients who underwent surgery for advanced gastric cancer. The association of fibrinogen levels with clinical/pathological findings and clinical outcome was evaluated. RESULTS: There was a positive correlation between plasma fibrinogen levels and the depth of invasion (p < 0.05). Hyperfibrinogenemia (>310 mg/dl) was independently associated with lymph node (Odds Ratio; 2.342, P = 0.0032) and liver (Odds Ratio; 2.933, P = 0.0147) metastasis, not with peritoneal metastasis in this series. Patients with hyperfibrinogenemia showed worse clinical outcome in T2 gastric cancer, however, there was no correlation of plasma fibrinogen level with prognosis in T3/T4 gastric cancer. CONCLUSION: Our results might support the idea that hyperfibrinogenemia can augment lymphatic and hematogeneous metastasis of advanced gastric cancer, which is major determinant of the prognosis in T2 gastric cancer. Therefore, in the situation without peritoneal involvement, hyperfibrinogenemia is a useful biomarker to predict the possible metastasis and worse clinical outcome in T2 gastric cancer

Reduced expression of tissue factor pathway inhibitor-2 contributes to apoptosis and angiogenesis in cervical cancer

<p>Abstract</p> <p>Background</p> <p>Tissue factor pathway inhibitor-2 (TFPI-2) is an extracellular matrix associated broad-spectrum Kunitz-type serine proteinase inhibitor. Recently, down regulation of TFPI-2 was suggested to be involved in tumor invasion and metastasis in some cancers.</p> <p>Methods</p> <p>This study involved 12 normal cervical squamous epithelia, 48 cervical intraepithelial neoplasia (CIN), and 68 cervical cancer. The expression of TFPI-2, Ki-67 and vascular endothelial growth factor (VEGF) were investigated by immunohistochemistry staining. The apoptolic index(AI) was determined with an in situ end-labeling assay(TUNEL). And the marker of CD34 staining was used as an indicator of microvessel density (MVD).</p> <p>Results</p> <p>TFPI-2 expression has a decreasing trend with the progression of cervical cancer and was significantly correlated with FIGO stage, lymph node metastasis and HPV infection. In addition, there were significant positive correlations between the grading of TFPI-2 expression and AI(P = 0.004). In contrast, the expression of TFPI-2 and VEGF or MVD was negatively correlated (both p < 0.001). However, we did not establish any significant correlation between Ki-67 and TFPI-2 expression in cervical cancer.</p> <p>Conclusions</p> <p>The results suggested that the expression of TFPI-2 had a decreasing trend with tumor progression of cervical cancer. There was a close association between the expression of TFPI-2 and tumor cell apoptosis and angiogenesis in patients with cervical cancer. TFPI-2 may play an inhibitive role during the development of cervical cancer.</p

TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Epigenetic silencing of tumor suppressor genes play important roles in NPC tumorgenesis. Tissue factor pathway inhibitor-2 (TFPI-2), is a protease inhibitor. Recently, <it>TFPI-2 </it>was suggested to be a tumor suppressor gene involved in tumorigenesis and metastasis in some cancers. In this study, we investigated whether <it>TFPI-2 </it>was inactivated epigenetically in nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>Transcriptional expression levels of <it>TFPI-2 </it>was evaluated by RT-PCR. Methylation status were investigated by methylation specific PCR and bisulfate genomic sequencing. The role of <it>TFPI-2 </it>as a tumor suppressor gene in NPC was addressed by re-introducing <it>TFPI-2 </it>expression into the NPC cell line CNE2.</p> <p>Results</p> <p><it>TFPI-2 </it>mRNA transcription was inactivated in NPC cell lines. <it>TFPI-2 </it>was aberrantly methylated in 66.7% (4/6) NPC cell lines and 88.6% (62/70) of NPC primary tumors, but not in normal nasopharyngeal epithelia. <it>TFPI-2 </it>expression could be restored in NPC cells after demethylation treatment. Ectopic expression of TFPI-2 in NPC cells induced apoptosis and inhibited cell proliferation, colony formation and cell migration.</p> <p>Conclusions</p> <p>Epigenetic inactivation of <it>TFPI-2 </it>by promoter hypermethylation is a frequent and tumor specific event in NPC. <it>TFPI-2 </it>might be considering as a putative tumor suppressor gene in NPC.</p

Expression and methylation status of tissue factor pathway inhibitor-2 gene in non-small-cell lung cancer

Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor that inhibits plasmin-dependent activation of several metalloproteinases. Downregulation of TFPI-2 could thus enhance the invasive potential of neoplastic cells in several cancers, including lung cancer. In this study, TFPI-2 mRNA was measured using a real-time PCR method in tumours of 59 patients with non-small-cell lung cancer (NSCLC). Tumour TFPI-2 mRNA levels appeared well correlated with protein expression evaluated by immunohistochemistry and were 4–120 times lower compared to those of nonaffected lung tissue in 22 cases (37%). Hypermethylation of the TFPI-2 gene promoter was demonstrated by restriction enzyme-polymerase chain reaction in 12 of 40 cases of NSCLC (30%), including nine of 17 for whom tumour TFPI-2 gene expression was lower than in noncancerous tissue. In contrast, this epigenetic modification was shown in only three of 23 tumours in which no decrease in TFPI-2 synthesis was found (P=0.016). Decreased TFPI-2 gene expression and hypermethylation were more frequently associated with stages III or IV NSCLC (eight out of 10, P=0.02) and the TFPI-2 gene promoter was more frequently hypermethylated in patients with lymph node metastases (eight out of 16, P=0.02). These results suggest that silencing of the TFPI-2 gene by hypermethylation might contribute to tumour progression in NSCLC