''cell'' in circulation 3 in preoperative patients. Moreover, the To detect hepatocellular carcinoma (HCC) cells in the significant elevation of serum AFP protein levels sometimes circulating peripheral blood, we previously designed a lags behind the formation of a considerable recurrent mass. highly sensitive reverse-transcription polymerase chainBecause of the recent advances in the reverse-transcription reaction (RT-PCR) method targeting a-fetoprotein polymerase chain reaction (RT-PCR) technology, several (AFP) messenger RNA (mRNA). Using this method, we studies have been performed for detecting cancer cells in analyzed peripheral blood of in-and out-patients bearlymph nodes or peripheral blood in the form of specific ing HCC for 2 months consecutively and examined the mRNA, the existence of which means the presence of cells outcome thereafter. All 11 patients with recurrence eiproducing the mRNA. Such a system has been developed for ther in the liver alone or in both the liver and the lung melanoma cells, 4 breast cancer cells, 5 prostate cancer cells, 6 were positive for AFP mRNA. Among 10 recurrence-free and neuroblastoma cells. 7 Kar et al. 8,9 and Hillaire et al. 10 patients, 2 patients were AFP mRNA-negative and redetected the presence of albumin mRNA in peripheral blood mained recurrence-free during a period of 22 months of patients with HCC. But because a small amount of albumin observed. Four of 8 AFP mRNA-positive, recurrencemessage seems to be transcribed in nucleated blood cells, 3 free patients developed a clinically evident recurrence Matsumura et al. developed a RT-PCR system to detect AFP in the liver after 2 to 16 months. Seven of 8 preoperative mRNA in peripheral blood of HCC-bearing patients in 1994. 3 patients were already positive for AFP mRNA and the However, the serum AFP protein level in their HCC patients remaining negative patient became positive during surwas as high as 62,738 { 7,031 ng/mL, whereas the overall gery. Four of 6 preoperatively positive and still-alive papositive rate was 52%. For the practical usage in therapeutic tients had recurrence in the liver after 2 to 9 months.decision-making and early detection of recurrence, we conNone of the HCC-negative patients were positive for AFP structed an original, easy, and far more sensitive RT-PCR mRNA. We actually found an AFP protein-positive cell system for detecting AFP mRNA in circulation. 11 With this in peripheral blood obtained from one of the AFP method, only a single high-AFP-producing cell in 1 cc of whole mRNA-positive patients by immunostaining. The presblood was recognizable within 12 hours. 11 In the previous ent results suggest that circulating HCC cells may have study, using this system, we found five of seven HCC patients some relationship with the recurrence of HCC in the to be positive for AFP mRNA in their peripheral blood, liver. (HEPATOLOGY 1997;25:564-568.) whereas four patients with positive hepatitis virus marker(s) but negative for HCC and a healthy volunteer were negative. Hepatocellular carcinoma (HCC...

Summary A highly sensitive system was previously developed by us to detect the presence of colorectal carcinoma cells in blood in the form of cytokeratin 20 (CK20) mRNA. In the present study, we used an improved version of this system to analyse the peripheral blood of 28 patients with colorectal carcinoma, five patients with non-cancerous intestinal diseases and six normal controls for the presence or absence of CK20 mRNA and to investigate the relationship between the mRNA results and prognosis. All eight patients with recurrence were positive for CK20 mRNA, as were four patients in the Dukes' C stage with either distant metastasis or dissemination. Five of the nine patients in the Dukes' C stage with neither distant metastasis nor dissemination were positive, and three of these developed recurrence within 11 months after the analysis. Only one of the seven patients in the Dukes' A or B stage was positive, and none showed recurrence during the 1-19 months of observation. None of the five patients without carcinomas or of the six normal controls was positive. Although the follow-up period is limited and the recurrences were all local at present, these results suggest that the presence of CK20 mRNA in circulation may be a useful indicator for the screening of advanced colorectal carcinoma patients with a high risk of recurrence.

No abstract

We present a rat model in which continuous supply of hepatocyte growth factor (HGF) prevents liver injury induced by carbon tetrachloride (CCl4) and E. coli 011:B4 lipopolysaccharide (LPS). Rat fibroblasts genetically modified to secrete rat HGF were implanted in syngenic rat spleen 7 days before administration of the hepatotoxins. Rats with HGF‐secreting fibroblasts in the spleen showed a dramatic resistance to CCl4‐ and LPS‐induced liver injury. In the LPS‐induced liver injury model, blood chemical analysis revealed that the increase in serum glutamic oxalacetic transaminase level and the decrease in blood sugar level were remarkably suppressed in rats with HGF‐secreting cells in the spleen. Most importantly, their survival rate was greatly improved compared to other control groups of rats. Thus our results indicate a new role of HGF in liver protection during endotoxemia and convey important clinical implications for developing new therapeutic modalities in the treatment of liver failure caused by endotoxemia.

No abstract