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Continuous therapy with cytotoxic drugs suppresses humoral immune function and may result in local infection. We present a case of orbital apex syndrome caused by Aspergillus infection during chemotherapy for metastatic colorectal cancer. A 74-year-old man with colorectal liver metastases under long-term continuous systemic chemotherapy presented with painful, progressive orbital apex syndrome. Magnetic resonance imaging disclosed a small enhancing lesion around the right ethmoid sinus. We initially diagnosed colorectal cancer metastasis and he underwent biopsy via the endoscopic endonasal transethmoid approach. However, pathological examination of the cultured specimen revealed Aspergillus fumigatus. The patient was treated with voriconazole and the orbital apex syndrome resolved after 1 month. Orbital aspergillosis is a life-threatening disease and should be listed as a differential diagnosis of uncommon local infections during continuous chemotherapy.

DNA methylation is a common epigenetic change in cancer. However, microRNA (miRNA) regulation by epigenetic alteration, especially CpG island hypermethylation, remains poorly understood in esophageal squamous cell carcinoma (ESCC).miRNAs which were up-regulated after de-methylation with 5-aza-2'-deoxycytidine (5-AZA) were analyzed using the Human miFinder 384HC miScript miRNA PCR Array. The DNA methylation level was evaluated by bisulfite-pyrosequencing assay.In two of the cell lines, 20 miRNAs, including miR-145-5p, were found to be up-regulated by more than three-fold after 5-AZA treatment. The miRNA-145 promoter was significantly more hypermethylated in the cancer tissues than in matched normal adjacent esophageal epithelial mucosa (p=0.0042; paired t-test). Moreover, the miRNA-145-5p expression levels were significantly lower in cancerous tissues (p=0.0024).miRNA-145 expression in ESCC seems to be regulated by hypermethylation of the miRNA-145 promoter region.

High mobility group 1 (HMGB1) is a highly conserved non-histone nucleosomal protein in mammals. We investigated the clinical significance of HMGB1 expression in colorectal cancer (CRC).The expression of HMGB1 mRNA in 140 tumor and normal tissues from CRC patients was examined by quantitative real-time polymerase chain reaction (PCR). We immunohistochemically investigated HMGB1 expression in tumor and metastatic lymph nodes in CRC.HMGB1 expression was significantly higher in tumor than in normal tissues. High HMGB1 expression was associated with larger tumor volumes, higher rates of lymphatic invasion, more frequent lymph node metastases and poorer prognoses for overall survival. Multivariate analyses showed that HMGB1 expression was an independent prognostic indicator of overall survival. Immunocytochemical analysis revealed that HMGB1 was overexpressed in both CRC tissues and regional lymph node metastases.Investigating HMGB1 expression may be a predictor of postoperative lymph node metastasis and prognosis in CRC.

Tenascin-C (TNC) is an extracellular matrix glycoprotein, usually derived from myofibroblasts in the cancer microenvironment. Recently, however, the significance of tumor-derived TNC in initiation of cancer metastasis was disclosed. We investigated the clinical significance of cancer-derived TNC in colorectal cancer (CRC) cases.TNC expression in 170 cases of CRC was analyzed by quantitative real-time polymerase chain reaction (PCR). In addition, gene expression arrays using purely-separated cancer tissues of another 86 cases was performed and the functional implications of cancer-specific TNC were investigated.The expression of TNC mRNA was significantly higher in CRC tissues than in the corresponding normal tissues. Cancer cell-specific TNC expression was a significant prognostic factor in CRC cases. Moreover, cancer cell-derived TNC was associated with the epithelial-mesenchymal transition (EMT) signature.Cancer cell-derived TNC promotes cancer invasiveness via EMT regulation, and not cancer tissue TNC but cancer cell-specific TNC is a novel indicator of poor prognosis.

The expression of Wingless/int-1 (Wnt)-induced secreted protein-1 (WISP-1/CCN4), a member of the Cyr61-CTGF-Nov (CCN) family, has been examined in several types of cancer. However, the correlation between the WISP-1 expression and the clinical features of esophageal squamous cell carcinoma (ESCC) remain to be elucidated. This study aimed to clarify the expression of WISP-1 protein in patients with ESCC and also to examine the function of WISP-1 in esophageal cancer cells in vitro.One-hundred and ninety patients with thoracic esophageal carcinoma underwent transthoracic subtotal esophagectomy-between 2005 and 2009. All patients that had received previous therapy were excluded and 105 out of the 190 ESCC samples were analyzed immunohistochemically using WISP-1 antibody. The expression of WISP-1 mRNA in esophageal cancer cell lines was analyzed by RT-PCR. Growth assay and invasion assays were performed using WISP-1 transfected cells.The immunohistochemical analysis showed that WISP-1-positive cases were closely associated with tumor size, tumor type, lymph node metastasis and poor prognosis. There were significantly more WISP-1-positive infiltrative type tumors than expanding type tumors. In the esophageal cancer cell lines examined, only TE8 expressed WISP-1 mRNA. The growth of WISP-1-transfected cells was significantly increased in comparison to the control cells, but no differences in the invasion activity were observed between the transfected cells and control cells.The expression of WISP-1 may play an important role in the progression of ESCC. WISP-1 could therefore be a clinical marker for a poor prognosis in patients with ESCC and may also be a therapeutic target to control the progression of ESCC.