No abstract

BackgroundPredictive biomarkers for the recurrence of hepatocellular carcinoma (HCC) have great benefit in the selection of treatment options, including liver transplantation (LT), for HCC. The purpose of this study was to identify specific microRNAs (miRs) in exosomes from the serum of patients with recurrent HCC and to validate these molecules as novel biomarkers for HCC recurrence.MethodsWe employed microarray-based expression profiling of miRs derived from exosomes in the serum of HCC patients to identify a biomarker that distinguishes between patients with and without HCC recurrence after LT. This was followed by the validation in a separate cohort of 59 HCC patients who underwent living related LT. The functions and potential gene targets of the recurrence-specific miRs were analysed using a database, clinical samples and HCC cell lines.ResultsWe found that miR-718 showed significantly different expression in the serum exosomes of HCC cases with recurrence after LT compared with those without recurrence. Decreased expression of miR-718 was associated with HCC tumour aggressiveness in the validated cohort series. We identified HOXB8 as a potential target gene of miR-718, and its upregulation was associated with poor prognosis.ConclusionCirculating miRs in serum exosomes have potential as novel biomarkers for predicting HCC recurrence.

It has been shown that RT-PCR is a powerful tool to detect CEA mRNA in the lymph nodes or the peripheral blood. This is potentially very useful to determine high-risk patients for metastasis. Serial analysis is warranted to assess the long-term significance of this method and its therapeutic and prognostic implications.

Detection of the mRNA of selected genes by reverse transcriptase-polymerase chain reaction (RT-PCR) is a sensitive and powerful tool for detecting cancer cells in bone-marrow or peripheral-blood samples. In this study, we determined whether carcinoembryonic antigen (CEA) mRNA is detectable in the peripheral blood of patients with gastrointestinal or breast cancer. In addition, we studied selected patients undergoing surgical procedures to assess whether tumor manipulation during operation enhances cancer-cell dissemination. Peripheral blood from 55 patients with gastrointestinal or breast cancer and from 22 control cases was analysed for CEA mRNA using RT-PCR. For 15 selected cases undergoing curative surgery for cancer, samples were also obtained during and after surgery. Breast cancer is conceptually accepted by many investigators as a systemic disease (Brown et al., 1995;Cote et al., 1991). This means that early breast cancer or minimum-sized breast cancer can spread via the blood-stream or lymphatic system to form metastatic foci in distant organs. We have considered that the same situation might exist in gastrointestinal cancers. It was, however, difficult to prove this concept due to the limitcd techniques available. Reccnt dcvelopments in molecular technology now enable us to detect small numbers of circulating cancer cclls in the peripheral blood or bone marrow (Johnson et a/., 1995; Smith et al., 1991).In this study, we detccted the presence of carcinoembryonic antigen ( 1995). If CEA mRNA is detected in blood samples, this implies the presence of ectopic, and hence presumably malignant CEA-expressing cells. One potential problem is that the CEA gene family includes a number of homologous genes partly expressed in granulocytes, which may produce falsepositive results (Stoffel et al., 1993). To overcome this problem, CEA-specific amplification has been developed using welldesigned DNA primers (Gerhard et al., Neumaier el al., 1995). On the basis of the results obtained in our present study, we discuss the significance of the presence of CEA mRNA in the peripheral blood of patients. In addition, to examine the effect of tumor manipulation during operation (Brown et ab, 1995; Nishizaki et aL, 1990), we applied the RT-PCR assay to peripheral blood samples taken from patients before, during and after operation. MATERIAL A N D METHODS PatientsFifty-five patients aged between 31 and 76 years were evaluated; these included 6 with esophageal cancer, 20 with gastric cancer, 20 with colorectal cancer and 9 with breast cancer. Of these, 14 patients including 7 with stage-IV gastric cancer, 6 with Dukes' D colorectal cancer and 1 with stage-IV breast cancer were shown to have distant metastases which were confirmed by chest X-ray, computed tomography, magnetic resonance imaging or ultrasonography. In these 14 advanced cases, a simple resection of the primary lesion was performed in 2 of 7 cases of gastric cancer, 4 of 6 cases of colorcctal cancer and 1 case of breast cancer. The other 7 far advanced cases receive...

No abstract

We previously developed γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) as a tool to detect viable cancer cells, based on the fact that the enzyme γ-glutamyltranspeptidase (GGT) is overexpressed on membranes of various cancer cells, but is not expressed in normal tissue. Cleavage of the probe by GGT generates green fluorescence. Here, we examined the feasibility of clinical application of gGlu-HMRG during breast-conserving surgery. We found that fluorescence derived from cleavage of gGlu-HMRG allowed easy discrimination of breast tumors, even those smaller than 1 mm in size, from normal mammary gland tissues, with 92% sensitivity and 94% specificity, within only 5 min after application. We believe this rapid, low-cost method represents a breakthrough in intraoperative margin assessment during breast-conserving surgery.

Summary Loss of sequences from human chromosome 10q has been reported in several different cancers. Recently, a second candidate tumour-suppressor gene, DMBT1, was identified in this chromosomal region. We studied the mRNA expression and homozygous deletion of this gene in human oesophageal, gastric and colon cancers. Reverse transcriptase polymerase chain reaction (RT-PCR) amplification demonstrated that 23 (53.5%) of 43 oesophageal, 5 (12.5%) of 40 gastric, and 4 (16.7%) of 24 colorectal cancer cases showed an apparent reduction in DMBT1 mRNA in tumour tissues compared with paired normal tissues. Twelve out of 15 oesophageal cancer cell lines also showed no expression. We next studied homozygous deletions within the DMBT1 gene in oesophageal cancers by using duplex PCR. Consequently, it was recognized in five (11.6%) of the primary tumours and two (13.3%) of the cell lines. These findings suggest that DMBT1 may act as a tumour-suppressor gene not only in brain tumours but also in gastrointestinal cancers, especially in oesophageal cancers.

Background/Aims-Matrix metalloproteinase-7 (MMP-7) belongs to the same family as matrix degrading metalloproteinase (MMPs)