During mammalian development, many cells are programmed to die most mediated by apoptosis. The Fas antigen coded by the structural gene for mouse lymphoproliferation mutation (lpr), is a cell surface protein belonging to the tumour necrosis factor/nerve growth factor receptor family, and mediates apoptosis. The Fas antigen messenger RNA is expressed in the thymus, liver, heart, lung and ovary. We prepared a monoclonal antibody against mouse Fas antigen, which immunoprecipitated the antigen (M(r) 45K) and had cytolytic activity against cell lines expressing mouse Fas antigen. We report here that staining of mouse thymocytes with the antibody indicated that thymocytes from the wild-type and lprcg mice expressed the Fas antigen, whereas little expression of the Fas antigen was found in lpr mice. Intraperitoneal administration of the anti-Fas antibody into mice rapidly killed the wild-type mice but neither lpr nor lprcg mice. Biochemical, histological and electron microscope analyses indicated severe damage of the liver by apoptosis. These findings suggest that the Fas antigen is important in programmed cell death in the liver, and may be involved in fulminant hepatitis in some cases.

Intraoperative imprint cytology is a useful method for evaluating the status of sentinel nodes and is more accurate than frozen-section analysis. In addition, imprint cytology can detect micrometastasis more accurately than conventional haematoxylin and eosin-stained sectioning.

Summary MDM2 is an oncoprotein that inhibits p53 tumour-suppressor protein. Amplification of the MDM2 gene and overexpression of its protein have been observed in some human malignancies, and these abnormalities have a role in tumorigenesis through inactivation of p53 function. To determine the clinicopathological and prognostic value of MDM2 abnormalities in non-small-cell lung cancer (NSCLC), MDM2 gene amplification and its protein expression status were analysed in surgically resected materials. MDM2 gene amplification was detected in only 2 (7%) of the 30 tested patients. MDM2 protein was found immunohistochemically in a total of 48 (24%) of the 201 patients. MDM2 protein was slightly frequently observed in patients with adenocarcinoma, but its presence or absence was not associated with clinicopathological factors such as T-factor, N-factor, stage, tumour size, differentiation or p53 protein status. Overall, MDM2-positive patients tended to have a better prognosis (P = 0.062). In particular, among immunohistochemically p53-negative patients (n = 110), those with positive MDM2 protein expression showed significantly better prognosis (P = 0.039) and, in a multivariate analysis, MDM2 protein status was a favourable prognostic factor (P = 0.037). In contrast, among p53-positive patients (n = 91), there was no difference in prognosis depending on MDM2 protein status. Thus, in the NSCLC patients studied, MDM2 gene amplification was a minor event, but expression of its protein, which was often observed immunohistochemically, was a favourable prognostic marker, especially among patients without p53 protein accumulation. Further study is needed to determine how MDM2 protein expression results in a better prognosis.Keywords: MDM2 gene; non-small-cell lung cancer; p53; prognosis; immunohistochemistry; amplification; fluorescence-based polymerase chain reaction single-strand conformation polymorphism The MDM2 gene was originally identified and cloned by amplification in a transformed tumorigenic Balb/c 3T3 fibroblast cell line (Cahilly-Snyder et al, 1987;Fakharzadeh et al, 1991;Oliner et al, 1992). Its product, p90, is now considered to form a tight complex with both the wild-type and mutant p53 tumour-suppressor gene protein and to inactivate wild-type p53 function by masking the Nterminal acidic transactivating domain of p53 protein, indicating that abnormalities of the MDM2 gene may be closely associated with tumorigenesis and/or tumour development (Olson et al, 1993; Haines et al, 1994). Indeed, MDM2 gene amplification and overexpression of its product have been described in several types of malignancies in humans. However, the clinicopathological role of these abnormalities has yet to be determined.In lung cancer, p53 abnormalities have been well examined but, to our knowledge, MDM2 abnormalities in this disease have been reported only by Marchetti et al (1995a

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Pancreatic ductal adenocarcinoma (PDAC) shows the worst mortality rate among common malignancies, with a 5-year survival rate of only 4%, and the majority of PDAC patients are diagnosed at an advanced stage in which no effective therapy is available at present. Although the proportion of curable cases is still not so high, surgical resection of early stage PDAC is the only way to cure the disease. Hence, establishment of a screening strategy to detect early stage PDAC by novel serological markers is required urgently, and development of novel molecular therapies for PDAC treatment is also eagerly expected. We here report overexpression of REG4, a new member of the regenerating islet-derived (REG) family, in PDAC cells on the basis of genome-wide cDNA microarray analysis as well as reverse transcription-polymerase chain reaction and immunohistochemical analysis. We also detected significant elevation of REG4 in the serum of some patients with early-stage PDAC using our enzymelinked immunosorbent assay system, indicating the possibility of REG4 as a new serological marker of PDAC. Furthermore, we found that knockdown of endogenous REG4 expression in PDAC cell lines with small interfering RNA caused a decrease in cell viability. Concordantly, addition of recombinant REG4 to the culture medium enhanced growth of a PDAC cell line in a dose-dependent manner. A monoclonal antibody against REG4 neutralized its growth-promoting effects and attenuated significantly the growth of PDAC cells. These findings indicate that REG4 is a promising tumor marker to screen early-stage PDAC, and also that neutralization of REG4 by the antibody may offer novel potential tools for the treatment of PDAC. (Cancer Sci 2006; 97: 1191-1197) P ancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the western world and shows the worst mortality among common malignancies, with a 5-year survival rate of only 4%.(1,2) In 2006, it is estimated that approximately 33 730 new cases of pancreatic cancer will be diagnosed in the USA, with 32 300 of these people expected to die of the disease. In Japan nearly 20 000 PDAC patients die each year. Because the majority of PDAC patients are diagnosed at an advanced stage, no effective therapy to cure the disease is available at present. Several approaches that combine surgery with chemotherapy, including 5-fluorouracil (5-FU) or gemcitabine, with or without radiation, may improve patients' quality of life, (1,2) but those treatments have a very limited effect on long-term survival of PDAC patients due to its extremely aggressive and chemoresistant nature.The very poor prognosis of PDAC arises from several reasons, including the difficulty of detecting PDAC at an early stage.(1,2) Despite improvements in diagnostic imaging techniques, such as endoscopic ultrasound and magnetic resonance cholangiopancreatography,(1,2) most patients do not undergo imaging procedures because they do not have any symptoms until late in the course of the disease. An accurate and easy serological tes...

Sentinel node biopsy guided by indocyanin green dye is an easy technique with an acceptable success rate in detecting sentinel nodes and predicting axillary nodal status. Axillary node status, the presence or absence of lymphatic or vascular invasion in the tumor and patient age affect its success in identifying sentinel nodes.

We conclude that the new definitions of PanIN and IPMN improve the consistency in classifying these lesions, but additional work is needed to further improve the reproducibility of their classification.

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