Outcomes of hepatic artery infusion therapy for hepatic metastases from colorectal carcinoma after radiological placement of infusion catheters.

AIM: The aim of this study is to evaluate the safety and efficacy of hepatic artery infusion (HAI) of 5-fluorouracil (5FU) for patients with liver metastases from colorectal carcinoma after radiological placement of infusion catheters. METHODS: Forty-two patients with liver metastases from colorectal carcinoma received radiological placement of infusion catheters using the distal fixation method. They received continuous HAI of 5FU 1,000-1,500mg for 5h weekly or biweekly. Tumor status was assessed by chest-abdominal computed tomography (CT) scan after every 10 infusions. Hepatic perfusion was checked by CT arteriography via the infusion port after every 10 infusions. RESULTS: Radiological placements of catheters were performed successfully in all cases. Each patient received an average of 36 treatments (range: 10-98). Catheter failure was found in 3 patients (7.1%). Nine incidents of grade 1 toxicity were observed in 8 patients (19.0%). There was a complete response in 6 patients, partial remission in 18, stable disease in 9, and progression of disease in 9 (response rate: 57.1%). Overall median survival time was 29.1 months. Using Cox's proportional hazard model, lymph node metastases in primary colorectal carcinoma and pre-treatment serum CEA affected overall survival (P=0.011, P=0.005). CONCLUSIONS: HAI after radiological placement of infusion catheters is a safe and effective treatment particularly for patients with no lymph node metastasis in primary carcinoma or with a low pre-treatment serum CEA level.

Gene expression analysis from nuclear Poly(A) RNA.

Quantitation of the level of specific mRNA involves the isolation of total RNA or poly(A)+ RNA as a starting materiaL Thus, this result is the sum of the transcription and degradation of mRNA. Here we report a rapid, sensitive, and high-throughput methodology for gene expression analysis from nuclear poly(A)+ RNA via the reduction of the cytosolic components. The cells were first trapped on the glass fiber membranes of 96-well filter plates and subsequently exposed to non-ionic detergent to achieve cell membrane permeation. The cytosolic components, which contain preexisting mRNA, were removed by washing with the appropriate buffer, while nuclei remained in the filter plates. Lysis buffer was then used to release nuclear mRNA, which was collected on oligo(dT)-immobilized PCR plates for the capture of poly(A)+ RNA, on which RT-PCR was performed. The reduction of the cytosolic components and the preservation of the nuclear components were confirmed by electron microscopy, agarose gel electrophoresis, PCR of mtDNA, and RT-PCR of pre-splicing immature beta-actin poly(A)+ RNA. Using this method, we clearly identified UVC-induced p21 gene expression that is not detectable with conventional whole cell methods.

Cyclooxygenase-2 overexpression correlates with tumour recurrence, especially haematogenous metastasis, of colorectal cancer.

Epidemiological studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs), known to inhibit cyclooxygenase (COX), reduce the risk of colorectal cancer. COX is a key enzyme in prostaglandin biosynthesis, and two isoforms of COX, COX-1 and COX-2, have been identified. Recently COX-2 has been reported to frequently overexpress in colorectal neoplasms and to play a role in colorectal tumorigenesis and tumour progression. In this study, using immunohistochemistry, we examined COX-2 expression in advanced human colorectal cancer and its correlation with clinicopathological features. COX-2 expression was observed mainly in the cytoplasm of cancer cells in all the specimens examined, but some stromal cells and endothelial cells were also stained. According to the grade of COX-2 expression of the cancer cells, patients were divided into high- and low-COX-2 expression groups. High-COX-2 expression significantly correlated with tumour recurrence, especially haematogenous metastasis. These results suggest that a selective COX-2 inhibitor can be a novel class of therapeutic agents not only for tumorigenesis but also for haematogenous metastasis of colorectal cancer. To our knowledge, this is the first report on the correlation between COX-2 overexpression and recurrence of colorectal cancer.

MMP-1 is a prognostic marker for hematogenous metastasis of colorectal cancer.

BACKGROUND: Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be an essential step in the complicated process of hematogenous metastasis. MMP-1 is a member of collagenases, a family of MMPs that degrades collagens type I, II, and III, main components of the interstitial stroma. The purpose of this study was to investigate the expression of MMP-1 in colorectal cancer and its correlation with hematogenous metastasis. Patients and Methods. We examined 133 cases of colorectal cancer (Dukes A: 72; Dukes B: 26; Dukes C: 23; Dukes D: 12). Sections were cut from formalin-fixed, paraffin-embedded samples containing the deepest site of cancer invasion and stained immunohistochemically with a monoclonal antibody to MMP-1. According to the area of the tumor that was stained, patients were divided into high- and low-MMP-1 expression groups. RESULTS: MMP-1 expression was observed in the cytoplasm of cancer cells, some stromal cells, and a few normal epithelial cells of colonic mucosa. High MMP-1 expression was found in 47 (35.3%) cases and low in 86 (64.7%). Hematogenous metastasis was identified in 14 (29.8%) of high-MMP-1 groups and 12 (13.9%) of low-MMP-1 groups. MMP-1 expression significantly correlated with hematogenous metastasis of colorectal cancer, but no correlation was found between MMP-1 expression and the other clinicopathological features investigated. CONCLUSIONS: MMP-1 expression may be a novel marker for hematogenous metastasis of colorectal cancer, and its inhibition may be a strategy for prevention of metastasis.

Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522.

It is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characterized, COX-1 and COX-2. Multiple studies have shown that COX-2 is expressed at high levels in colorectal tumours and play a role in colorectal tumorigenesis. Recently it has been reported that selective inhibition of COX-2 inhibits colon cancer cell growth. In this study we investigated the effect of a selective COX-2 inhibitor (JTE-522) on haematogenous metastasis of colon cancer. For this purpose, we selected a murine colon cancer cell line, colon-26, that constitutively expresses the COX-2 protein. The subclone P expressed a high level of COX-2 and the subclone 5 expressed a low level. The colon-26 subclones were injected into the tail vein of BALB/c mice. JTE-522 was given intraperitoneally every day from the day prior to cancer cell injection, and the mice were sacrificed 16 days after cell injection. Lung metastases were compared between groups with and without JTE-522. In the mice injected with subclone P, the number of lung metastatic nodules was significantly reduced in the treated group. However, in the mice injected with subclone 5, there was little difference between the control and the treated groups. These results indicate that there may be a direct link between inhibition of haematogenous metastasis of colon cancer and selective inhibition of COX-2, and that selective COX-2 inhibitors may be a novel class of therapeutic agents not only for colorectal tumorigenesis but also for haematogenous metastasis of colon cancer.

A schwannoma of the cecum: case report and review of Japanese schwannomas in the large intestine.

A 66-year-old Japanese man had a positive fecal occult blood test at a regular check-up, and a large polypoid mass was detected in the cecum by barium enema study. Colonoscopy showed a submucosal tumor with ulcer protruding into the cecal lumen. A large-forceps biopsy specimen was taken from the bottom of the ulcer. With the tentative diagnosis of neurogenic tumor, ileocecal resection was performed. The tumor showed spindle-cell proliferation in a concentric or fascicular pattern. Immunohistochemically, the tumor cells were diffusely positive for S-100 protein, and they had intracytoplasmic periodic acid Schiff (PAS)-positive crystalloids. The mitosis count was low (about 1 per 20 high-power fields). The pathological diagnosis of this tumor was benign gastrointestinal schwannoma. A large number of schwannoma cases have been reported since 1910 when Verocay reported it as a true tumor that stemmed from Schwann cells and did not contain neuroganglion cells. However, gastrointestinal schwannomas are rare, and schwannomas of the large intestine are extremely rare. We reviewed 40 cases already reported in Japan and this present case in order to clarify the clinicopathological features of this tumor.