MAGE1及NCAM在人小细胞肺癌中的表达

目的研究黑色素瘤抗原基因-1（MAGE1）及神经细胞粘附分子（NCAM）在小细胞肺癌NCI—H446细胞株及其裸鼠原位移植瘤、皮下瘤组织内的表达水平及分布特征。方法人小细胞肺癌细胞株NCI—H446细胞株及其裸鼠原位移植瘤组织行免疫组化染色，观察MAGE1及NCAM分别在小细胞肺癌的分布情况。免疫印迹法比较上述两种抗原在体内外蛋白中表达水平的高低。结果MAGE1及NCAM在NCI—H446细胞株及其裸鼠原位移植瘤组织的细胞膜及细胞浆中表达，并且体内外表达无明显差异。结论MAGE1及NCAM在人小细胞肺癌NCI—H446细胞内及肿瘤组织内呈稳定高表达，这两种抗原有望成为小细胞肺癌的靶点。     

The role of NCAM in remyelination

The neural cell adhesion molecule (NCAM) is expressed by myelinating precursor cells in neonatal mouse spinal cord and by remyelinating cells after chemically induced demyelination in adult mouse. It shows tempting suggestions about its possible involvement in the reparative mechanisms and the remyelination processes that take place in multiple sclerosis (MS). In fact, its levels progressively increase in the cerebrospinal fluid (CSF) of acute MS patients subjected to steroid treatment, paralleling the progressive clinical improvement after the attack. Such an increase is not found in nacute MS patients not treated with steroids nor in non-acute patients subjected to the same steroid treatment. Received: 15 June 2001 / Accepted in revised form: 24 January 2002     

Intrahepatic cholangiocarcinoma arising in chronic advanced liver disease and the cholangiocarcinomatous component of hepatocellular cholangiocarcinoma share common phenotypes and cholangiocarcinogenesis

Xu J, Sasaki M, Harada K, Sato Y, Ikeda H, Kim J‐H, Yu E & Nakanuma Y
(2011) Histopathology  59 , 1090–1099
Intrahepatic cholangiocarcinoma arising in chronic advanced liver disease and the cholangiocarcinomatous component of hepatocellular cholangiocarcinoma share common phenotypes and cholangiocarcinogenesis Aims: Intrahepatic cholangiocarcinomas (ICCs) are known to arise in cases of non‐biliary, chronic advanced liver disease (CALD), but their clinicopathological features remain unexplored. The aim of this study was to compare the histological and immunohistochemical ICCs arising inCALD with those arising in livers with non‐specific reactive (NSR) changes. Methods and results: Seventy‐one cases of ICC arising in CALD were compared with ICCs arising in livers with NSR changes, including normal livers (72 cases) and the cholangiocarcinomatous (CC) component of hepatocellular cholangioncarcinomas (HC‐CCs) (30 cases). The expression of mucin was higher in ICC with NSR changes, whereas it was relatively low in ICC with CALD and the CC component of HC‐CC. The expression of biliary markers [cytokeratin (CK)7, CK19, epithelial membrane antigen, and epithelial cell adhesion molecule (EpCAM)] was lower in CC with CALD and in the CC component of HC‐CC than in CC with NSR changes. The expression of hepatic progenitor cell markers [neural cell adhesion molecule (NCAM) and c‐kit] was higher in ICC with CALD and the CC component of HC‐CC than in ICC with NSR changes. EpCAM and CK19 were constantly expressed in cultured CC cells, whereas NCAM was infrequently expressed in cultured CC cells. Conclusions: The carcinogenesis of ICC arising in CALD and the ICC component of HC‐CC, each showing similar features, may involve hepatic progenitor cells.     

Chronic morphine treatment increases the expression of the neural cell adhesion molecule in the dorsal horn of the mouse spinal cord

It is well known that prolonged exposure to morphine results in tolerance to morphine-induced antinociception. In the present study, we found that mice that were tolerant to morphine-induced antinociception exhibited an increase in immunoreactivity for the neural cell adhesion molecule in the dorsal horn of the spinal cord, which was highly overlapped with immunoreactivity for the increased metabotropic glutamate receptor 5 induced by morphine. These findings support the idea that repeated stimulation of μ-opioid receptors increases the expression of neural cell adhesion molecule and metabotropic glutamate receptor 5. This phenomenon leads to the enhanced excitatory synaptic transmission in the dorsal horn of the spinal cord, and in turn suppresses the morphine-induced antinociception.     

Identification of CD56 and CD57 by flow cytometry in Ewing’s sarcoma or primitive neuroectodermal tumor

 CD56 and CD57 are commonly considered as natural killer and neuroectodermal markers, but their expression has been identified in a wide spectrum of neoplasms including some cases of Ewing’s sarcoma (ES) and primitive neuroectodermal tumor (PNET). We report two cases of small, round blue cell tumor (SRBCT), in which flow cytometry immunophenotyping (FCI) detected strong expression of CD56 and CD57 (one case). Immunohistochemical staining with Leu-19 and Leu-7 confirmed the FI results. Although CD56 and CD57 expression is consistent with ES/PNET, it can be potentially misleading if results of FCI are interpreted in the absence of other findings. These cases suggest the utility of FCI in undifferentiated SRBCT. The literature on CD56 and CD57 expression in ES/PNET is reviewed and discussed. Received: 5 January 1998 / Accepted: 19 February 1998     

NCAM in developing mouse gonads and ducts

Summary The expression of theNeuralCell AdhesionMolecule, NCAM, in mouse gonads and ducts was studied from fetal life to maturity. The methods used were immunocytochemical staining and Western blotting. The immunocytochemical studies showed that the only structures that remain NCAM-positive throughout life were the mesonephric-derived rete ovarii and rete testis. Also in the fetal gonads some somatic cell lining the groups of differentiating germ cells were stained. In the immature as well as in the mature ovary the granulosa cells and oocytes of growing and large follicles — but not of small follicles — were stained. A particularly strong staining of the cytoplasm of the oocyte, healthy as well as atretic, was seen. All cells of the testis remained negative except for weakly stained residual bodies and late spermatids. At all ages the male ducts showed only weak staining, whereas in the female Müllerian duct the epithelium became strongly positive at puberty. The stroma of the Müllerian duct was positive during a transitory period around day 16 of fetal life in both sexes. One-dimensional gel immunoblotting of total protein from gonads, rete and ducts from immature and mature mice showed that only the two largest isoforms of NCAM (NCAM-A and NCAM-B) were present. The gonads and the rete of both sexes and the adult uterus expressed only NCAM-B, whereas NCAM-A was also detected in the adult epididymis. The present findings suggest that NCAM may be involved in the normal development and formation of both the gonads and ducts. In particular, NCAM may play a part in sustaining the integrity of the rete testis, thus ensuring the pathway for spermatozoa from the testis to the epididymis. Furthermore this cell adhesion molecule may also be important for follicular growth and differentiation.     

Neural cell adhesion molecule immunoreactivity in Merkel cells and Merkel cell tumours

We have analysed the expression of the neural cell adhesion molecule (NCAM) in normal Merkel cells of pig and human skin, and in nine neuroendocrine carcinomas of the skin (Merkel cell carcinomas). NCAM immunoreactivity was observed in virtually all Merkel cells, both in epidermis and vibrissae of pig snout skin and in human epidermis. Immunostaining surrounded the entire surface of Merkel cells and was not restricted to the contact areas between Merkel cells and nerve terminals. All Merkel cell carcinomas studied were also positive for NCAM. The immunostaining pattern of the tumour cells was similar to that observed in normal Merkel cells; the immunoreactivity was confined to the cell membranes. These results suggest that NCAM may be used as an immunohistochemical marker for both Merkel cells and Merkel cell tumours.     

Cell-cell interaction modulates neuroectodermal specification of embryonic stem cells

The controlled differentiation of embryonic stem (ES) cells is of utmost interest to their clinical, biotechnological, and basic science use. Many investigators have combinatorially assessed the role of specific soluble factors and extracellular matrices in guiding ES cell fate, yet the interaction between neighboring cells in these heterogeneous cultures has been poorly defined due to a lack of conventional tools to specifically uncouple these variables. Herein, we explored the role of cell-cell interactions during neuroectodermal specification of ES cells using a microfabricated cell pair array. We tracked differentiation events in situ, using an ES cell line expressing green fluorescent protein (GFP) under the regulation of the Sox1 gene promoter, an early marker of neuroectodermal germ cell commitment in the adult forebrain. We observed that a previously specified Sox1-GFP+ cell could induce the specification of an undifferentiated ES cell. This induction was modulated by the two cells being in contact and was dependent on the age of previously specified cell prior to coculture. A screen of candidate cell adhesion molecules revealed that the expression of connexin (Cx)-43 correlated with the age-dependent effect of cell contact in cell pair experiments. ES cells deficient in Cx-43 showed aberrant neuroectodermal specification and lineage commitment, highlighting the importance of gap junctional signaling in the development of this germ layer. Moreover, this study demonstrates the integration of microscale culture techniques to explore the biology of ES cells and gain insight into relevant developmental processes otherwise undefined due to bulk culture methods.     

Expression of growth associated protein 43 and neural cell adhesion molecule in congenital fibre type disproportion with interstitial myositis

We report on the expression of growth associated protein (GAP)43 and neural cell adhesion molecule (NCAM) in congenital fibre type disproportion (CFTD) with myopathological additional signs of interstitial myositis. We assume that sarcolemmal GAP43 in developmental disordered myocytes plays a role in maintenance of growth morphology. In muscular dystrophy light microscopical evaluation reveals no GAP43 immunoreactivity in regenerating fibres. The expression of GAP43 seems to be a characteristic feature of CFTD. The expression of NCAM, particularly in the sarcolemma of small muscle fibres of CFTD, indicates a functional state of permanent partial denervation. Whether the steroid-responsive interstitial myositis is pathogenetically related to CFTD or a coincidental inflammation is not known. Because of the clinical and myopathological data the differential diagnosis of Emery-Dreifuss muscular dystrophy is considered.