Biomedical subjects

Yoshitaka Hishikawa

Publications and source records attributed to Yoshitaka Hishikawa.

At least 19 recordsLinked to original sources

PubMed2006

Identification of estrogen receptor beta-positive intraepithelial lymphocytes and their possible roles in normal and tubal pregnancy oviducts.

BACKGROUND: Although intraepithelial lymphocytes (IELs) in human oviductal epithelium have been implicated in the regulation of local immunity, the precise kinetics and mechanism of steroid regulation of IEL are largely unknown. METHODS: We examined the localization of estrogen receptors (ERs) and progesterone receptors (PRs) in 41 human oviducts by immunohistochemistry. These tissues were obtained from various menstrual cycles, also from both post-menopausal women and tubal pregnancies. The expressions of ERbeta mRNA and membrane (m)PR mRNA were examined by in situ hybridization and RT-PCR, respectively. RESULTS: Most of the IEL expressed ERbeta at both mRNA and protein levels. The number of ERbeta-positive IEL, which were identified as CD8-positive T lymphocytes and also were mPR positive, was increased in the late proliferative, the mid-secretory and late secretory phases in normally cycling women (P < 0.05). Interestingly, in tubal pregnancy, ERbeta-positive IELs were consistently abundant. In addition, we found a high Ki-67-labelling index for IEL, although ERalpha was entirely absent in the tubal pregnancy oviducts. CONCLUSIONS: These results suggest that the number of IEL fluctuated because of estrogen and progesterone levels probably through ERbeta and mPR, respectively. ERbeta-positive IEL may be involved in regulating immune tolerance in tubal pregnancy oviducts.

Adult↗

PubMed2006

Diethylstilbestrol increases the density of prolactin cells in male mouse pituitary by inducing proliferation of prolactin cells and transdifferentiation of gonadotropic cells.

Diethylstilbestrol (DES) has been implicated in mammalian abnormalities. We examined the effects of DES on follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) cells in the pituitaries of male mice treated with various doses of DES for 20 days. DES reduced the density of FSH and LH cells in a dose-dependent manner, but increased that of PRL cells. When the expression of estrogen receptor (ER) alpha and beta was assessed, an induction of ERbeta by DES was found predominantly in PRL cells. However, since these effects were abolished in ERalpha knockout mice, DES appears to act primarily through ERalpha. When the expression of Ki-67 and Pit-1 in PRL cells was examined at various time-points after DES treatment, some PRL cells became Ki-67 positive at 10-15 days, and Pit-1-positive cells were increased at 5-15 days. Furthermore, some FSH and LH cells became Pit-1 positive, and co-localized with PRL at 5-10 days. Our results indicate that DES increases PRL cells by inducing proliferation of PRL cells and transdifferentiation of FSH/LH cells to PRL cells.

Animals↗

PubMed2006

Expression of the Snurf-Snrpn IC transcript in the oocyte and its putative role in the imprinting establishment of the mouse 7C imprinting domain.

The human chromosome 15q11-q13, or mouse chromosome 7C, is an imprinting domain controlled by bipartite imprinting centers (ICs): Prader-Willi syndrome (PWS)-IC and Angelman syndrome (AS)-IC. PWS-IC functions to maintain the paternal epigenotype on the paternal chromosome in somatic cells, while AS-IC plays a role in the establishment of the maternal epigenetic mark at PWS-IC in the female germline or early embryos. Several alternative exons and promoters of Snurf-Snrpn (SNRPN upstream reading frame-small nuclear ribonucleoprotein polypeptide N) are expressed as "IC transcripts". Previous studies have shown that IC-transcript expression is restricted to the brain. We studied expression of the mouse IC-transcript in tissues including brain and oocytes as well as in cultured neurons and glia cells by RT-PCR and by in situ hybridization (ISH) in oocytes. The IC transcript was strongly expressed in brain (especially in neurons) and ovary (especially in oocytes and granulosa cells), while no expression was found in other tissues. This was confirmed by quantitative analysis and ISH. Expression levels in the brain were 7-fold higher compared to those in ovaries. ISH signals were observed in oocytes and granulosa cells of the secondary and developing follicles. These findings, together with previous data, suggest that the IC transcript may be associated with the establishment of PWS-IC methylation on the maternal chromosome as an AS-IC cis-acting element.

Alternative Splicing↗

PubMed2005

Induction of cell death in rat small intestine by ischemia reperfusion: differential roles of Fas/Fas ligand and Bcl-2/Bax systems depending upon cell types.

Although ischemia reperfusion (I/R) induces apoptotic damage of mammalian small intestine, the molecular mechanism is largely unknown. We investigated the appearance of apoptosis at various time-points (0-24 h) of reperfusion after 1-h ischemia and the expression of various apoptosis-related proteins, such as Bcl-2, Bax, Fas, Fas ligand (FasL), activated caspase-3, and cytochrome c, immunohistochemically in rat small intestine. As assessed by TUNEL and electron microscopy, apoptotic cells were increased at 3 h of reperfusion in all intestinal parts (villous epithelium, crypt epithelium, and stroma of intestine). Moreover, the TUNEL-positive cells in the stroma were later identified as T cells. The expression of Fas and FasL as well as activated caspase-3 was markedly increased at 3 h of reperfusion in the stroma. In the villous epithelium, a transient decrease in Bcl-2 expression was found while in the crypt epithelium, Fas expression was induced. Finally, intraperitoneal injection of leupeptin (an SH-protease inhibitor) after I/R resulted in a significant inhibition of the induction of apoptosis in the stroma and crypt epithelium. Our results indicate that the triggering molecules of apoptosis in the I/R rat small intestine may vary depending on cell type and that the use of a broad-spectrum protease inhibitor may reduce intestinal damage.

Animals↗

PubMed2005

Overexpression of macrophage migration inhibitory factor induces angiogenesis and deteriorates prognosis after radical resection for hepatocellular carcinoma.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pivotal cytokine that regulates inflammatory and immune responses. Recently, many investigators reported that MIF is expressed highly in several tumors, including hepatocellular carcinoma (HCC). However, the role of MIF in tumor angiogenesis and patient prognosis has not been examined in patients with HCC. METHODS: The authors evaluated MIF expression in 56 samples of HCC by Western blot analysis, and the results were correlated with clinicopathologic factors and patient prognosis. MIF localization was determined by immunohistochemical methods, and the results were compared with tumor microvessel density (MVD), as assessed by anti-CD34 antibody. Furthermore, to validate the role of MIF in angiogenesis, both MIF expression during culture of HCC cells (using the Hep3B, HepG2, and Huh7 cell lines) under hypoxic condition and the angiogenic potential of recombinant MIF in an in vitro angiogenic model were examined. RESULTS: Tumors with high MIF expression had high alpha-fetoprotein levels (P = 0.049) and frequent intrahepatic recurrence (P = 0.043). Immunohistochemical MIF scores had a significant correlation with MVD (P = 0.007). Patients who had tumors with high MIF expression levels had a significantly worse (P = 0.025) disease-free survival, and this finding remained significant as an independent prognostic factor in the multivariate analysis. Hep3B cells had high expression of MIF at 6 hours and 12 hours after hypoxic stress and exogenous MIF stimulated endothelial tube formation in in vitro angiogenesis. CONCLUSIONS: The current findings suggest that MIF expression may play a pivotal role in the dismal prognosis of patients with HCC that may be attributable to the modulation of angiogenesis.

Aged↗

PubMed2005

Pranlukast, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from leukotriene receptor antagonism.

BACKGROUND: Pranlukast, a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist, inhibits not only airway smooth muscle contraction, but also allergic inflammation. The aim of this study was to determine the mechanism of pranlukast-induced interleukin-5 (IL-5) inhibition in allergic inflammation. METHODS: Surgically resected human lung tissue was passively sensitized in vitro with mite-allergen-sensitized sera, followed by stimulation with mite allergen after pretreatment of the tissue with pranlukast, dexamethasone, or both. The IL-5 protein level in the culture medium was measured, and in situ hybridization of IL-5 and CysLTR1 mRNA was performed using lung tissues. RESULTS: Pretreatment of lung tissues with pranlukast alone significantly decreased the amount of IL-5 protein in the culture medium by 40%. The combination of pranlukast and dexamethasone synergistically enhanced this effect. Quantitative in situ hybridization with image analysis revealed abundant expression of IL-5 mRNA in eosinophils, lymphocytes, and mast cells in sensitized and allergen-stimulated lung tissues. CysLTR1 mRNA was detected in macrophages, smooth muscle cells, eosinophils, and mast cells, but was less expressed in lymphocytes. Pranlukast-induced inhibition of IL-5 mRNA expression was noted in various cells, irrespective of their CysLTR1 mRNA expression status. In addition, cysteinyl leukotrienes per se failed to upregulate the IL-5 production. CONCLUSION: Our results indicate that pranlukast inhibits IL-5 synthesis via a mechanism distinct from CysLTR1 antagonism.

Adult↗

PubMed2005

Enhanced expression of insulin-like growth factor-binding proteins in human osteoarthritic cartilage detected by immunohistochemistry and in situ hybridization.

OBJECTIVE: To determine the roles of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) in the pathogenesis of osteoarthritis (OA). DESIGN: Cartilage tissues were obtained from the femoral heads of patients with OA, and those from patients with femoral neck fractures were used as a control. The expression of IGFBP-3, -4, and -5 was examined using immunohistochemistry and in situ hybridization, and IGF-I and IGF-I receptors were also immunohistochemically detected. The percentages of positive chondrocytes were determined by counting the total number of chondrocytes over the area of the surface, middle, and deep zones of the cartilage. RESULTS: There was a marked increase in the percentage of positive chondrocytes in all IGFBPs on protein and messenger RNA levels for OA compared to that of the control cartilage. Furthermore, enhanced expression of IGFBPs and the IGF-I/IGF-I receptor was positively correlated with the histologic score for cartilage lesions. CONCLUSION: Up-regulation of IGFBPs as well as IGF-I and its receptor was observed for OA cartilage tissue, suggesting the involvement of IGFBPs in the pathogenesis of OA.

Adult↗

PubMed2004

Early human preantral follicles have relaxin and relaxin receptor (LGR7), and relaxin promotes their development.

The regulatory mechanisms of early follicle development are not clearly understood. Although relaxin is a peptide that controls cell proliferation and differentiation in many tissues, its role in human follicular development is unclear. In this study we cultured slices of human ovarian cortical tissue in the presence and absence of recombinant human relaxin. Ovarian tissue was obtained by biopsy during gynecological laparotomy or laparoscopy (14 women; mean age +/- sem, 29.0 +/- 6.1 yr; range, 17-37 yr). A significantly higher proportion of secondary follicles (14.5% vs. 5.0% in the control group; P < 0.01) and a significantly decreased proportion of primordial follicles (30.1% vs. 47.4% in the control group; P < 0.05) were found in tissues cultured with relaxin for 7 d. Immunocytochemical studies with the anti-C-peptide of prorelaxin and antirelaxin antibodies revealed the localization of relaxin in the oocyte and in flat pregranulosa and granulosa cells of primordial, primary, and secondary follicles. The presence of the relaxin receptor LGR7 was observed in flat pregranulosa and granulosa cells of primordial, primary, and secondary follicles by immunocytochemical and in situ hybridization analyses. These results suggest that relaxin plays a role through its receptor during the early stage of follicle development.

Adolescent↗

PubMed2004

Identification and localization of estrogen receptor alpha- and beta-positive cells in adult male and female mouse intestine at various estrogen levels.

Although estrogen is implicated in the regulation of mammalian intestinal function, the presence and the distribution of estrogen receptor (ER)-positive cells in the intestine are still controversial. The present study was designed to localize ERalpha- and ERbeta-expressing cells in female and male mouse intestines immunohistochemically under various estrogen conditions, especially in female mice, ovariectomized as well at various phases of the estrous cycle. Western blot analysis detected both ERalpha (66-kDa band) and ERbeta (56-kDa band). Immunohistochemical staining of paraffin-embedded sections after antigen-retrieval treatment with autoclaving revealed staining for ERalpha in submucosal interstitial cells, and double staining identified these cells as a subtype of intestinal macrophages. The number of these cells varied according to the estrous cycle phase. Administration of 17beta-estradiol to ovariectomized mice resulted in a significant increase in the number of ERalpha-positive macrophages. On the other hand, the nuclei of nerve cells in Auerbach and Meissner plexuses were positive for both ERalpha and ERbeta, but the number of positive nerve cells was not affected by estrogen. Our results indicate that estrogen and estrogenic compounds may exert their actions on the intestine in two ways; one is through interstitial macrophages and the other is through intestinal neurons.

Animals↗

PubMed2004

Expression of keratinocyte growth factor/fibroblast growth factor-7 and its receptor in human lung cancer: correlation with tumour proliferative activity and patient prognosis.

Keratinocyte growth factor (KGF)/fibroblast growth factor-7 (FGF-7), a mesenchymal cell-derived paracrine growth factor that specifically stimulates epithelial cell proliferation, has been implicated in the repair of lung tissue. The present study was designed to determine the expression and role of KGF and its receptor (KGFR) in human lung cancer tissues, particularly in relation to cancer cell kinetics and prognosis. Thirty-one adenocarcinomas and 30 squamous cell carcinomas, and ten normal lung tissues as a control, were examined. The expression of KGF and KGFR proteins was examined using rabbit polyclonal anti-human KGF and anti-human KGFR antisera raised in the authors' laboratories against synthetic peptides corresponding to parts of human KGF KGFR, respectively. Their specificity was confirmed in lung tumour tissues by western blotting various controls. Proliferative activity was assessed by determining the labelling index (LI) for Ki-67 antigen. Immunohistochemistry revealed that tissue co-expression of KGF KGFR correlated significantly with higher differentiation grades in squamous cell carcinoma. Conversely, in adenocarcinoma, co-expression correlated with lower differentiation grades high Ki-67 LI, was significantly associated with lymph node metastasis shorter 5-year survival. Therefore, the results indicate that co-expression of KGF KGFR correlates significantly with poor prognosis in adenocarcinoma, but not in squamous cell carcinoma, of the lung.

Adenocarcinoma↗

PubMed2004

Estrogen receptor-associated expression of keratinocyte growth factor and its possible role in the inhibition of apoptosis in human breast cancer.

Although estrogen is known to play a crucial role in the pathogenesis of breast cancer, the molecular mechanisms underlying the action of estrogen remain elusive. In the present study, we focused on keratinocyte growth factor (KGF) and its receptor (KGFR) in the pathogenesis of breast cancer, as a growth factor mediating estrogen action, since significant roles of KGF were demonstrated in various steroid hormone-dependent tissues. First, using paraffin-embedded specimens from 42 breast cancer patients, we examined expression patterns of KGF and KGFR by both immunohistochemistry using newly generated antibodies and nonradioactive in situ hybridization with T-T dimerized synthetic oligonucleotide probes. We next compared the results with the expression of estrogen receptor (ER) alpha and beta, proliferative activity and apoptotic frequency (TUNEL staining). Also, the similar approaches were taken to analyze the expression and role of KGF in ER-positive (MCF7, ZR-75-1) and ER-negative (SK-BR-3, MDA-MB-231) human breast cancer cell lines in vitro. In the surgical specimens, KGF was expressed in cancer cells as well as stromal cells in 19/42 cases (45%), while KGFR was found in cancer cells in 24/42 cases (57%). The distribution of protein and mRNA in the analysis of both KGF and KGFR expression generally coincided. Moreover, KGF expression was closely associated with the expression of ER alpha, and the coexpression of KGF and KGFR significantly correlated with lower TUNEL index, but not with proliferative activity. In accordance with the in vivo findings, KGF expression was detected only in ER alpha-positive MCF7 and ZR-75-1 cells in vitro. And more importantly, we found the inhibitory effect of KGF upon the induction of apoptosis by anticancer drugs in MCF7 cells. Collectively, our results indicate that ER alpha may be involved in KGF expression, and that KGF may play antiapoptotic roles, rather than mitogenic, in human breast cancer.

Adenocarcinoma↗

PubMed2004

Expression of keratinocyte growth factor and its receptor in human breast cancer: its inhibitory role in the induction of apoptosis possibly through the overexpression of Bcl-2.

Keratinocyte growth factor (KGF), a mesenchymal cell derived paracrine growth factor that regulates normal epithelial cell proliferation, appears to be an essential mediator of steroids in various reproductive organs. The present study was designed to determine the expression and role of KGF and its receptor (KGFR) in human breast carcinoma tissues by immunohistochemistry. We also compared the results with the expression of estrogen receptor alpha(ERalpha), ERbeta, the proliferative activity assessed by the labeling index (LI) for the Ki-67 antigen, apoptotic frequency assessed by terminal dUTP nick end-labeling (TUNEL) index, and the expression of Bcl-2. All of KGF-positive cases were ERalpha- positive (p<0.05), but not that of ERbeta, while all of KGFR-positive cases were ERbeta-positive (p<0.05), but not that of ERalpha. The specimens with the coexpression of KGF and KGFR significantly correlated with a lower TUNEL index (p<0.05), but not with Ki-67 LI in breast cancer tissues. Further analysis at the cellular level revealed that Bcl-2 was colocalized in KGFR-positive cells, and these cells were almost negative for TUNEL staining. Bcl-2-positive cells were also associated with ERbeta, as expected. Therefore, the results indicate that ERalpha may be involved in KGF expression, and that the coexpression of KGF and KGFR may play an inhibitory role in the induction of apoptosis possibly through the up-regulation of Bcl-2 expression in human breast cancer.

Adult↗

PubMed2003

Complement C4b-binding protein as a novel murine epididymal secretory protein.

Complement C4b-binding protein (C4BP) is a plasma protein synthesized in the liver and plays a regulatory role in the host defense complement system. We have previously reported that mRNAs of the C4BP alpha chain (C4BPalpha) are expressed at significant levels in the guinea pig and mouse epididymis in an androgen-dependent manner. Here, we analyze the murine C4bpa gene and show that epididymal and liver C4BPalpha mRNAs are generated from a single-copy gene and that the epididymal C4BPalpha mRNAs are transcribed from novel transcription start sites located approximately 100 base pairs downstream from those used in the liver. Furthermore, in an immunohistochemical study using rabbit anti-mouse C4BP antiserum, we demonstrated that C4BP is localized in the stereocilia and Golgi apparatus of the epididymal epithelial cells and the surfaces of spermatozoa in the lumen in the region from the distal caput to the cauda but not in the proximal caput region. Indirect immunofluorescence of the isolated spermatozoa demonstrated that C4BP is localized preferentially on the head region of the spermatozoa, and immunoelectron microscopy located C4BP on the plasma membrane and the outer acrosomal membrane. These results indicate that epididymal C4BP is synthesized in the epithelial cells and secreted into the lumen in a region-restricted manner and is taken up to the sperm membranes on passage through the epididymis. Many epididymal proteins are secreted from the epithelial cells in a region-specific and androgen-dependent manner and are considered to contribute to sperm maturation. Our findings suggest a novel function of C4BP as one such epididymal secretory protein.

Animals↗

PubMed2003

Molecular histochemical analysis of estrogen receptor alpha and beta expressions in the mouse ovary: in situ hybridization and Southwestern histochemistry.

It is well known that estrogen plays important roles in the female reproductive organs, including the ovary, through estrogen receptors (ERalpha and ERbeta). It is suggested that selective effects of estrogen on a discrete set of genes may reside in promoters that are differentially responsive to ERalpha and ERbeta, while the relative biological significance of ERalpha and ERbeta is unclear. Therefore, for a better understanding of the physiological and pathological states of ovarian cells, it seems to be essential to analyze the cellular expression of ERalpha and ERbeta, at both the protein and mRNA levels. For this purpose, we have optimized the protocols for immunohistochemistry and nonradioactive in situ hybridization, respectively, using the mouse ovary. These techniques have been established as useful histochemical methods for the localization of specific protein and/or mRNA expression at the cellular level. Moreover, we also attempted to evaluate ERs as binding proteins to estrogen responsive elements, using Southwestern histochemistry, which permits us to analyze the localization in situ of transcription regulatory proteins. By employing these methods, more precise understanding of specific gene expression and evaluation of its biological significance in the ovary would be possible.

Animals↗

PubMed2003

Possible involvement of keratinocyte growth factor and its receptor in enhanced epithelial-cell proliferation and acquired recurrence of middle-ear cholesteatoma.

Middle-ear cholesteatoma is characterized by enhanced proliferation of epithelial cells and granular tissue formation. However, the molecular mechanism underlying these pathological changes is largely unknown. Keratinocyte growth factor (KGF) is a mesenchymal cell-derived paracrine growth factor that specifically stimulates epithelial cell proliferation. In the present study, we investigated the possible involvement of KGF and its receptor, KGFR, in the pathogenesis of cholesteatoma using in situ hybridization and immunohistochemistry, respectively. We examined 56 cholesteatoma specimens, and 8 normal skin areas as control. KGF and KGFR expression was examined by immunohistochemistry using rabbit anti-human KGF and anti-human KGFR polyclonal antisera raised in our laboratories against synthetic peptides corresponding to parts of human KGF and KGFR, respectively. KGF protein and mRNA were detected exclusively in stromal fibroblasts and infiltrating T lymphocytes in 80% of cholesteatoma cases, whereas KGFR protein and mRNA were localized in the epithelium in 72% of cases. Assessment of the proliferative activity of cholesteatoma using the labeling index for Ki-67 showed a significantly higher Ki-67 labeling index (66%) in KGF+/KGFR+ cases than other cases. There was a significant correlation between KGF+/KGFR+ expression and recurrence. Our results indicate the possible involvement of both KGF and KGFR in enhanced epithelial cell proliferative activity and recurrence of cholesteatoma.

Antibody Specificity↗

PubMed2003

Transforming growth factor-beta1 released from the spleen exerts a growth inhibitory effect on liver regeneration in rats.

Several previous reports indicated that partial hepatectomy (PH) when combined with splenectomy enhances the regenerative capacity of the liver, most probably due to the removal of unknown inhibitory factors released from the spleen. Transforming growth factor (TGF)-beta1 is a major antiproliferative factor for the hepatocytes, and the role of splenic TGF-beta1 in liver regeneration is yet to be clarified. The splenic expression of TGF-beta1 and its secretion into the portal circulation from the spleen were evaluated in a standardized two-thirds hepatectomy model in rats. Rats in the control group underwent only the hepatectomy, while splenectomy was added in the splenectomy group. The hepatocyte proliferation rate was assessed by proliferating cell nuclear antigen (PCNA) immunostaining, and the results were compared with the TGF-beta1 kinetics in the portal blood. Significant increase in PCNA index and decrease in portal TGF-beta1 level were noticed in the splenectomy group at 48 hours after PH compared with the control group. Both TGF-beta1 protein and mRNA expression level in the spleen were strongest at 48 hours after PH and coincided with the peak of the plasma TGF-beta1 level. TGF-beta type II receptor (TbetaR-II) expression in the liver after PH was assessed immunohistochemically. The expression of TbetaR-II decreased at 12 hours and returned to preoperative level at 24 hours after PH in both groups. The changes of TbetaR-II expression were similar in both groups, and the significant difference was not observed at 48 hours after PH. Namely, splenectomy did not alter the expression of TbetaR-II in remnant liver at the peak of hepatocytes proliferation. In conclusion we found that TGF-beta1 was produced and secreted by the spleen during the early phase of liver regeneration and removal of the spleen enhanced proliferation of hepatocytes. Splenectomy thus may exert a salutary effect in selected patients with jeopardized regenerative capacity of the liver.

Animals↗

PubMed2003

Expression of tumor-associated membrane antigen, RCAS1, in human colorectal carcinomas and possible role in apoptosis of tumor-infiltrating lymphocytes.

RCAS1, a novel tumor-associated antigen, is expressed in advanced human neoplasias including uterine and ovarian carcinomas. RCAS1 protein was indicated to induce cell cycle arrest and apoptosis of cultured human lymphoid and myeloid cell lines and normal lymphocytes. In the present study, we investigated the expression and prognostic value of RCAS1 in 58 patients with colorectal carcinomas. RCAS1 protein was detected by immunoperoxidase staining using a mouse monoclonal anti-RCAS1 antibody (22-1-1 antibody). Immunohistochemical examination showed expression of RCAS1 in 75% of colorectal carcinomas with lymph node metastases (n = 24), whereas it was present in only 41% of tumors without metastases (n = 34, P <.05). Patients with RCAS1-positive tumors showed a significantly poorer prognosis than those negative for RCAS1 (P <.05). Multivariate analysis using the Cox regression model indicated that RCAS1 positivity was an independent negative predictor for survival (P =.0300; risk ratio, 0.496). In addition, apoptotic cells of tumor-infiltrating lymphocytes were examined using nonradioactive in situ nick translation in paraffin-embedded sections. The proportion of apoptotic tumor-infiltrating lymphocytes was significantly higher in RCAS1-positive colorectal carcinomas (11.2 +/- 1.0) than in RCAS1-negative tumors (7.9 +/- 1.0, P <.05). Our results suggest that overexpression of RCAS1 may negatively affect the prognosis of human colorectal carcinomas and that RCAS1 may play a role in tumor immune privilege in vivo.

Adenocarcinoma↗

PubMed2003

Zone-dependent expression of estrogen receptors alpha and beta in human benign prostatic hyperplasia.

Estrogen, which acts through estrogen receptors (ERs) alpha and beta, has been implicated in the pathogenesis of benign and malignant human prostatic tumors, i.e. benign prostatic hyperplasia and prostate cancer, thought to originate from different zones of the prostate [the transition zone (TZ) and peripheral zone (PZ), respectively]. Here, we examined the cellular distribution of ERalpha and ERbeta in human normal and hyperplastic prostate tissues, using in situ hybridization and immunohistochemistry. ERalpha expression was restricted to stromal cells of PZ. In contrast, ERbeta was expressed in the stromal cells of PZ as well as TZ. ERbeta-positive epithelial cells were evenly distributed in PZ and TZ of the prostate. Our results suggest that estrogen may play a crucial role in the pathogenesis of benign prostatic hyperplasia through ERbeta.

Aged↗