Andreas Bastian

Increased Expression of RelA/Nuclear Factor-κB Protein Correlates with Colorectal Tumorigenesis

Objective: To identify the role of RelA/nuclear factor-ĸB, an important inhibitor of apoptosis in colorectal tumorigenesis, we examined the expression of RelA in normal colorectal mucosa (n = 10), colorectal adenomas (n = 30) and colorectal adenocarcinomas (n = 30). Furthermore, the association of RelA expression with tumor cell apoptosis, proliferation, and expression of Bcl-2/Bcl-xL was also studied. Methods: Paraffin sections were stained with monoclonal antibodies directed against RelA, Bcl-2, Bcl-xL, and Ki-67 to assess protein expression patterns in normal, adenomatous and colon cancer tissue. Apoptotic cells were detected by terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling (TUNEL) using an in situ detection kit. Results: The results of immunohistochemical staining revealed that expression of RelA, Bcl-2, Bcl-xL, and Ki-67 labeling index (LI) significantly increased in the transition from adenoma with low dysplasia to adenocarcinoma. This transition was associated with a significant decrease in the apoptotic index (AI) and a significant increase in the Ki-67 LI. The expression of RelA correlated inversely with the AI and correlated positively with the expression of Bcl-2, Bcl-xL, and Ki-67 LI in the transition from low-grade dysplasia to adenocarcinoma. Conclusion: Our results suggest that increased expression of RelA/nuclear factor-ĸB plays an important role in the transition from colorectal adenoma with low-grade dysplasia to adenocarcinoma in the pathogenesis of colon cancer in humans.

The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cells

Background Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti‐inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase‐2 (COX‐2) negative colorectal cancer cell lines.

Ultraviolet A1-induced downregulation of human β-defensins and interleukin-6 and interleukin-8 correlates with clinical improvement in localized scleroderma

Background  In previous studies, distinct immunological abnormalities have been reported in localized scleroderma (LS). Several pro‐inflammatory cytokines have been demonstrated at increased levels in sera of patients with LS in parallel with disease activity. Human β‐defensins (hBDs) are peptides with antimicrobial activity, but have been also shown to be implicated in tissue injury, scarring and wound healing. hBD expression in LS, a condition resembling pathological scarring due to excessive stimulation of matrix synthesis and fibroblast activation, has so far not been investigated. Ultraviolet (UV) A1 phototherapy, the most recent advance in the treatment of LS, targets T‐cell dermal inflammatory infiltrates via induction of various cytokines and soluble factors besides well‐known effects on collagen metabolism.

Increased abundance of cyclooxygenase-2 correlates with vascular endothelial growth factor-A abundance and tumor angiogenesis in gastric cancer

To understand the role of cyclooxygenase-2 (COX-2) in gastric cancer, we examined the abundance of COX-2, vascular endothelial growth factor-A (VEGF-A), and CD34 in 45 surgically resected human gastric cancers and paired normal gastric mucosa by immunohistochemical analysis. In addition, the message RNA (mRNA) expression of COX-2 and VEGF-A was evaluated in ten fresh surgically resected human gastric cancers and paired normal gastric mucosas using semi-quantitative reverse transcriptional polymerase chain reaction analysis. Our results confirmed an increased abundance of COX-2 and VEGF-A, and the microvessel density, which was assessed by CD34 abundance, in gastric cancer tissues compared with normal paired mucosa. Abundance of COX-2 and VEGF-A was significantly associated with tumor-node-metastasis (TNM) stage (P<0.05) and lymph node metastasis (P<0.001). In addition, abundance of VEGF-A associates with distance metastasis. A significant correlation was found between COX-2 and VEGF-A abundances (P<0.001). Both abundance of COX-2 and VEGF-A were significantly correlated with microvessel density (P<0.001, respectively). In six of ten cancerous tissues and in one of ten paired normal mucosas, the mRNA expression of COX-2 and VEGF-A was detected in the same specimen. In one other cancerous tissue, only COX-2 mRNA was detected. This study indicates that COX-2 is related to tumor angiogenesis in gastric cancer. VEGF-A might play a main role in the COX-2 angiogenic pathway.

Increased expression of nuclear factor-κB/RelA is correlated with tumor angiogenesis in human colorectal cancer

Background and aimsRecent studies have shown that nuclear factor-κ B/RelA (NF-κ B/RelA) is involved in tumor angiogenesis. This study examined whether NF-κ B/RelA expression is associated with vascular endothelial growth factor (VEGF) expression and microvessel density in human colorectal cancer.Materials and methodsTen specimens from normal colorectal mucosa and 52 colorectal adenocarcinomas were obtained by surgery or endoscopy. Immunohistochemical expression of NF-κ B/RelA, VEGF, and CD34 was detected on paraffin-embedded tissue sections.ResultsNF-κ B/RelA and VEGF were significantly overexpressed and associated with microvessel density in colorectal cancer. A significant association was found between NF-κ B/RelA and VEGF expression. Clinicopathological features were not correlated with NF-κ B/RelA, VEGF expression, or microvessel density.ConclusionOur results suggest that increased expression of NF-κ B/RelA contributes to tumor angiogenesis in colorectal cancer. VEGF may play an important role in mediating the NF-κ B/RelA angiogenic pathway.

Inhibition of cytosolic phospholipase A2 mRNA expression: a novel mechanism for acetylsalicylic acid-mediated growth inhibition and apoptosis in colon cancer cells

Acetylsalicylic acid (ASA) has been confirmed to inhibit proliferation and to induce apoptosis in human colorectal cancer cells in vitro. However, the mechanism by which ASA exhibits antiproliferative and proapoptotic effects in cyclooxygenase 2 (COX-2)-negative cells remains to be further elucidated. In the present study, SW480, a COX-2-negative colon cancer cell line, was treated with various concentrations of ASA (0, 2.5, 5, and 10 mM). The antiproliferative and proapoptotic effects of ASA were confirmed by MTT assay, flow cytometry of propidium iodide (PI)-stained cells, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. After treatment with ASA, intracellular cyclic AMP (cAMP) levels were increased and the production of prostaglandin E2 (PGE2) was decreased. RT-PCR analysis revealed that treatment of ASA induced a concentration-dependent downregulation of cytosolic phospholipase A2 (cPLA2) mRNA expression in SW480 cells and also in two other colorectal cancer cell lines, Colo320 and HT-29 cells. Intracellular calcium levels were unaffected by ASA treatment. Our results indicate that the ASA-induced downregulation of cytosolic phospholipase A2 mRNA expression might be a novel mechanism for ASA-mediated growth inhibition and apoptosis in colon cancer cells.

Deletion of the FHIT gene in human colorectal cancer is independent of high-risk HPV infection.

AbstractBackground and aims. The fragile histidine triad (FHIT) gene, which is frequently lost in many cancers, has been identified as a candidate tumor suppressor gene at chromosome 3p locus 14.2. Human papillomaviruses (HPVs) are the major cause of cervical carcinoma and have been found to be able to integrate its genes into the chromosome 3 fragile site of cultured cells, deleting a piece of DNA which includes the FHIT gene. Materials and methods. We used nested reverse transcriptase PCR and DNA sequencing to evaluate 32 cases of colorectal adenocarcinoma and matched nearby normal tissues for aberrant transcripts of FHIT and infection of high-risk HPVs. Results. Aberrant transcripts of the FHIT gene were observed in 34.4% of colorectal adenocarcinoma and in 6.3% of matched nearby normal tissues. The HPV16 DNA was detected in 21.9% of colorectal adenocarcinomas and 3.1% of matched nearby normal tissues using PCR. Only two cases of colorectal adenocarcinoma contained both aberrant transcripts of FHIT and HPV16 infection. No HPV18 infection was detected in the present study. Conclusion. Our results indicate that alteration of the FHIT gene and HPV16 infection are important genetic events associated with colorectal adenocarcinoma. However, there is no correlation between FHIT abnormalities, clinicopathological features, and HPV16 infection in colorectal adenocarcinoma.

UVA1-induced decrease in dermal neuron-specific enolase (NSE) in acrosclerosis.

Besides its role in small-cell carcinoma of the lung, elevated serum levels of neuron-specific enolase (NSE) have recently been reported to be associated with autoimmune rheumatic disorders such as systemic sclerosis. Serum NSE seems to correlate with disease activity as well as Rodnan skin score. The aim of the study was to assess the neuromodulatory effects of conventional UVA1 phototherapy on acrosclerosis as an additional mechanism besides an assumed T cell apoptosis, collagenase induction and angiogenesis. Punch skin biopsies of acrosclerotic skin lesions taken before and after treatment from four patients were evaluated immunohistochemically for the presence of NSE, S100 and neurofilament. Immunolabeling revealed a UVA-induced decrease in dermal NSE expression. In contrast, no alteration in neurofilament+ cells could be detected. In line with the findings of a previous investigation, a high number of S100+ cells were detected in most specimens. We demonstrated a UVA1-induced reduction in dermal NSE levels correlating with a softening of former sclerotic lesions. Even though the origin and the functional mechanisms remain obscure, NSE might be relevant directly within sclerotic skin lesions and may possibly be used as a diagnostic marker at least in SSc-associated acrosclerotic skin.

Fibromatosis of the hand associated with EMO syndrome: A Case report

BackgroundEMO syndrome, defined as a triad including exophthalmus, pretibial myxedema and osteoarthropathia, is a rare condition in patients suffering from hyperthyreosis.Case presentationWe here describe an interesting case of EMO syndrome associated with unilateral fibromatosis of the hand and an initial stage of generalized myxedema of the skin. To our knowledge a similar case has not yet been described in literature though reports about associated fibromatosis, e.g. located retroperitoneally, already exist. Familiar explanations include its initiation by autoimmune processes or aberrant T-cell cytokine stimulation leading to an overwhelming production of glycosaminoglycans.ConclusionInterpreting our case in context with previous reports we conclude that associated fibromatosis induced by autoimmune processes may affect a variety of different localizations and therefore requires careful monitoring. A therapeutical attempt by using UVA1 irridation for pretibial myxedema remained without a satisfying regression.