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61.
Frequent co-localization of Cox-2 and laminin-5 gamma2 chain at the invasive front of early-stage lung adenocarcinomas 总被引:7,自引:0,他引:7
Niki T Kohno T Iba S Moriya Y Takahashi Y Saito M Maeshima A Yamada T Matsuno Y Fukayama M Yokota J Hirohashi S 《The American journal of pathology》2002,160(3):1129-1141
Laminin-5 is an extracellular matrix protein that plays a key role in cell migration and tumor invasion. Cox-2 is an induced isoform of cyclooxygenases that plays an important role in carcinogenesis, suppression of apoptosis, angiogenesis, and metastasis of colon cancer. We report frequent co-expression of cox-2 and laminin-5 at the invasive front of early-stage lung adenocarcinomas. We investigated the expression of cox-2 and laminin-5 immunohistochemically in 102 cases of small-sized lung adenocarcinoma (maximum dimension, 2 cm or less). Cox-2 and laminin-5 were expressed in 97 (95.1%) and 82 (80.4%) cases, respectively. Both were preferentially localized in cancer cells at the cancer-stroma interface, although cox-2 tended to show a diffuse staining pattern in some cases. A comparison of their staining patterns revealed a striking similarity in their distribution in 24 cases, and a partial overlap between their localization in another 20 cases. Moreover, an overall correlation was found between the expression levels of cox-2 and laminin-5 (P = 0.018). To gain insight into the mechanisms that regulate the expression of these proteins, we additionally studied their expression in 58 cases of stage I lung adenocarcinoma, in which p53 status was determined by immunohistochemistry, polymerase chain reaction-single strand conformation polymorphism analysis, and direct sequencing. The results showed that tumors with mutant p53 tended to express more cox-2 than those with wild-type p53 (P = 0.080). Also, tumors that overexpressed p53 had higher levels of cox-2 and laminin-5 than those without p53 overexpression (P = 0.032 and 0.047, respectively). Further immunohistochemical analysis showed that tumors that overexpressed both epidermal growth factor receptor (EGFR) and erbB-2 had higher levels of cox-2 and laminin-5 than those without concomitant overexpression of these proteins (P = 0.014 and P = 0.018, respectively). To see whether EGFR signaling is involved in cox-2 and laminin-5 expression, we further conducted in vitro analyses using six lung adenocarcinoma cell lines (A549, HLC-1, ABC-1, LC-2/ad, VMRC-LCD, and L27). Western blot analyses showed that cox-2 mRNA levels, and to a lesser extent laminin-5 gamma2 mRNA levels, correlated with the expression levels of erbB-2 and the phosphorylated form of MAPK/ERK-1/2 protein. The addition of transforming growth factor-alpha increased both cox-2 and laminin-5 gamma2 mRNA levels in A549, ABC-1, and L27 with different kinetics; the induction of cox-2 occurred earlier than that of laminin-5 gamma2. Finally, the migration of ABC-1 cells was inhibited by MAP kinase kinase inhibitor PD98059 and a selective cox-2 inhibitor NS-398. In contrast, the migration of A549 cells was inhibited by PD98059, but much less effectively by NS-398. These results suggest that co-stimulatory mechanisms may exist that increase the expression of cox-2 and laminin-5 at the invasive front of lung adenocarcinomas and that EGFR signaling could be one of the mechanisms. Further investigations are warranted concerning the role of cox-2 and laminin-5 in cancer cell invasion and the significance of p53 and EGFR signaling in the regulation of cox-2 and laminin-5 expression. 相似文献
62.
63.
Kawakubo Y Kishimoto H Sato Y Yanagimoto K Tsuruta T Ogawa Y Kameya T 《Virchows Archiv : an international journal of pathology》1999,434(2):109-115
Langerhans cell histiocytosis (LCH) has been thought to be a disorder of immune regulation, and increasingly, evidence showing
that the tissue damage in LCH involves lymphokines and pro-inflammatory cytokines is reported. We detected human cytomegalovirus
(HCMV)-DNA in LCH cells in the foci of LCH lesions by immunohistochemistry, in situ hybridization and PCR. HCMV was detected
in the nuclei and/or cytoplasm of LCH cells in 9 of 27 LCH cases by immunostaining. HCMV was probably an early antigen. In
situ hybridization revealed signals for HCMV-DNA only in the nuclei of LCH cells in 10 of the 27 LCH cases. PCR analysis was
performed in 20 of the LCH cases, and HCMV-DNA was detected in 7 of these. All 7 positive cases were also positive for HCMV
by ISH and IHC. These findings suggested that early phase infection or reactivation of HCMV occurred in the LCH lesions. HCMV
infection may be accompanied by impaired cytokine production. Our study also suggested a relationship between HCMV infection
and expression of TNFα. In tissues affected by LCH, dermatopathic lymphadenopathy or malignant fibrous histiocytoma and in
normal tissues no signals for Epstein-Barr virus-RNA were detected. These findings suggest that in some cases LCH is associated
with HCMV infection.
Received: 24 November 1998 / Accepted: 24 April 1998 相似文献
64.
Comparison of mutagenic potentials and mutation spectra of benzene metabolites using supF shuttle vectors in human cells 总被引:1,自引:0,他引:1
Benzene is a human leukemogen and the metabolites are thought to be deeply involved in benzene leukemogenesis. In a previous study we reported the molecular analysis of p-benzoquinone (p-BQ) mutagenesis by using a supF shuttle vector plasmid and here we report the mutagenesis of the other metabolites, hydroquinone (HQ) and trans, trans-muconaldehyde (MUC). HQ is a precursor of p-BQ and MUC is produced by a ring-opening metabolic pathway. We found that the HQ redox cycle produced an oxidative lesion in plasmid DNA and significant differences among the mutagenic potentials of MUC, HQ and p-BQ. HQ has stronger mutagenicity than the others. It is about 20 and 600 times stronger than p-BQ and MUC, respectively. Furthermore, we found notable differences in each mutational feature. The MUC mutational type was characterized by a high frequency of tandem base substitutions that could be due to crosslinks produced by its aldehyde moieties, while HQ was characterized by frequent deletion. This HQ feature is the same as in vivo benezene mutagenesis of Big Blue mice reported by Provost et al. in 1996 and is also quite similar to a hydrogen peroxide mutational feature. Therefore, we presume that HQ and reactive oxygen species may play an important role in benzene carcinogenesis. 相似文献
65.
Preparation of a protein micro-array using a photo-reactive polymer for a cell-adhesion assay 总被引:4,自引:0,他引:4
A protein micro-array, called a "cell chip" was constructed by using a photo-reactive polymer for a cell-adhesion assay. Various amounts of albumin or fibronectin were covalently immobilized on a polystyrene dish using a micro-spotter with a dip pen. First, poly(acrylic acid) carrying azidophenyl groups was synthesized as the photo-reactive polymer. Secondly, the aqueous solution of a photo-reactive polymer (several nanoliters) was cast using the dip pen of the micro-spotter and dried in air. Subsequently, aqueous solutions of proteins were cast on the same place using the micro-spotter. After drying, the dish was irradiated with ultraviolet light. Finally, the immobilization was confirmed by staining with a dye. The immobilization was stable even after washing with Tween-20. The protein-immobilized area depended on the manipulation of the micro-spotter and the size of the dip pen. Subsequently, cell adhesion on the photo-immobilized protein micro-array was investigated. The adhesion behavior of cells depended on the kind of immobilized proteins and the kind of cells. The protein micro-array will be useful for cell diagnosis and for the selection of biomaterials to regulate cell behavior. 相似文献
66.
67.
Kousuke Marutsuka Yoshihiro Hasui Yujiro Asada Seiji Naito Yukio Osada Akinobu Sumiyoshi 《Clinical & experimental metastasis》1995,13(2):116-122
Effects of suramin, a polysulfonated naphthylurea compound, on metastatic ability, proliferation, and production of plasminogen activators and plasminogen activator inhibitors were studied using the highly metastatic human renal cell carcinoma cell line, SN12C-PM6. After renal subscapular implantation of tumor cells in nude mice, suramin significantly inhibited metastasis of tumor cells to the lungs and liver. In vitro growth of tumour cells was inhibited by suramin in a dose-dependent manner, at relatively low doses (ID50 = 105 µg/ml). Plasminogen activator inhibitor type 2 (PAI-2) production by tumor cells was enhanced by suramin (100 µg/ml), whereas urokinase-type plasminogen activator (uPA) production was suppressed. Thus, the increase in PAI-2 and the decrease in uPA production correlated with the inhibitory effects on tumour growth and metastasis by suramin. Therefore suramin may be beneficial for the treatment of patients with an early stage of renal cancer with potential risk of metastasis. 相似文献
68.
69.
Masaki Iwai Yasutaka Ishu Yoshihiro Kitagawa Kazunobu Tada Motomu Kashiwadani Takeshi Okanoue Kei Kashima 《Medical molecular morphology》1993,26(3-4):207-210
The immunoreactivity of albumin (ALB) was observed in the hepatocytes of fetal rats on day 18 of gestation, and was especially observable in immature rough endoplasmic reticulum (rER) and Golgi apparatus (GA); by then, a small amount of silver grains of ALB mRNA could already be detected. Just after birth, immunoreactivity of ALB could be observed in fine granules or diffusely in all hepatocytes, and was present in rER and GA. One week after birth immunoreactivity of ALB was observed in all hepatocytes and was visible in developed rER and GA; the grains of ALB mRNA were present in all hepatocytes. 相似文献
70.
Yoshihiro Hasebe Keiko Izumitani Masao Torii Teiji Tsuruta 《Macromolecular chemistry and physics.》1990,191(1):107-119
1,2-Epoxycyclohexane ( 1 ) was found to behave differently from propylene oxide (PO) in polymerization reactions with organozinc compounds as initiators. A chair-type complex, [Zn-MP]2,2, is the only compound that shows high catalytic activity for both polymerization of 1 and PO, following an anionic coordination mechanism. On the other hand, the polymerization of 1 with ZnEt2 or (EtZnOMe)4 as initiator proceeds according to a cationic mechanism. Cationic polymerization of 1 with ZnEt2 has two modes of termination reaction resulting in the formation of terminal units containing vinyl ether and allyl ether moieties. The initiation and propagation mechanism of 1 by [Zn-MP]2;2 is similar to that of PO, but chain transfer reaction takes place in the polymerization of 1 owing to the low stability of the growing chain end. By using [Zn-MP]2,2 as initiator, it was possible to prepare a block copolymer consisting of an isotactic sequence of monomeric units of PO and a syndiotactic sequence of monomeric units of 1 . 相似文献