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Background To apply the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) technique to individualized tumor response testing (ITRT) in esophageal cancer, optimal exposure conditions that would permit us to predict the clinical response to the low-dose cisplatin (CDDP)/5-fluorouracil (5-FU) regimen and docetaxel (DOC) regimen were determined.

In esophageal cancer, lymphatic spread occurs more frequently and at an earlier stage than in other gastrointestinal cancers, and both preoperative and intraoperative diagnoses of lymph nodes metastases are sometimes incorrect. Our objective was to measure the sizes of lymphatic metastases and to examine the accuracy of clinical diagnosis of lymphatic spread in patients with squamous cell carcinoma of the esophagus. The sizes of 320 metastatic lymph nodes of 9254 dissected nodes from 92 consecutive esophagectomy patients over 1 year were measured and compared with the sizes of the actual metastases within the nodes. These data allowed investigation of the correct rate of preoperative diagnosis of lymph node metastasis. The mean diameter of the metastases was 4.8 mm, which was significantly smaller than that of the involved lymph nodes. Among the metastatic lymph nodes, 37.2% were less than 5 mm in diameter, and 63.1% of the metastases were less than 5 mm in diameter. The true-positive and true-negative diagnosis rate for all lymph node stations in three fields (neck, thorax, and abdomen) was only 23.2%, and the false-negative rate for diagnosis of lymph node metastasis was 53.7%. Two-thirds of involved lymph nodes had very small metastases (

Cytochrome P450 (CYP) 2E1 is induced by ethanol and is postulated to be a source of reactive oxygen species during alcoholic liver disease. However, there was no difference in liver pathology and radical formation between wild-type and CYP2E1 knockout mice fed ethanol. Other CYP isoforms may contribute these effects if CYP2E1 is inhibited or absent. The purpose of this study was, therefore, to determine if blocking most of the P450 isoforms with 1-aminobenzotriazole (ABT; 100 mg/kg i.g.), has any effect on liver damage and oxidative stress due to alcohol in rats and mice. Male C57BL/6 mice and Wistar rats were fed either high-fat control or ethanol-containing enteral diet for 4 weeks. ABT had a significant inhibitory effect on many P450 isoforms independent of concomitant alcohol administration. However, ABT did not protect against liver damage due to alcohol in either species. Indices of oxidative stress and inflammation were also similar in livers from vehicle-treated and ABT-treated animals fed ethanol. In summary, suppression of P450 activity with ABT had no apparent effect on oxidative stress caused by alcohol in both rats and mice. These data support the hypothesis that oxidative stress and liver damage can occur independently of CYP activities in both rats and mice during early alcohol-induced liver injury.

The regeneration of liver tissue following transplantation is often complicated by inflammation and tissue damage induced by a number of factors, including ischemia and reperfusion injury and immune reactions to the donor tissue. The purpose of the current study is to characterize the effects of T cell–mediated hepatitis induced by concanavalin A (ConA) on the regenerative response in vivo. Liver regeneration following a partial (70%) hepatectomy (pHx) was associated with elevations in serum enzymes and the induction of key cell cycle proteins (cyclin D, cyclin E, and Stat3) and hepatocyte proliferation. The induction of T cell–mediated hepatitis 4 days before pHx increased serum enzymes 48 hours after pHx, reduced early cyclin D expression and Stat3 activation, and suppressed hepatocyte proliferation. This inhibition of proliferation was also associated with increased expression of p21, the activation of Smad2, the induction of transforming growth factor beta and interferon gamma expression, and reduced hepatic interleukin 6 production. Moreover, the ConA pretreatment increased the numbers of separate oval cell-like CD117+ cells and hematopoietic-like Sca-1+ cell populations 48 hours following pHx. The depletion of natural killer (NK) cells, an important component of the innate immune response, did not affect liver injury or ConA-induced impairment of hepatocyte proliferation but did increase the numbers of both CD117-positive and Sca-1–positive cell populations. Finally, splenocytes isolated from ConA-pretreated mice exerted cytotoxicity toward autologous bone marrow cells in an NK cell–dependent manner. Conclusion: T cell–mediated hepatitis alters early cytokine responses, reduces hepatocellular regeneration, and induces NK cell–sensitive oval cell and hematopoietic-like cell expansion following pHx. (HEPATOLOGY 2007;46:229–241.)