Upregulation of CA 19-9 in the Mouse Kidney Following Unilateral Ureteral Obstruction

High serum levels of carbohydrate antigen19-9 (CA19-9) have been detected in patients with pancreatic cancer and described in several recent case reports of patients with hydronephrosis. However, the mechanism of high serum levels of CA19-9 among hydronephrosis cases remains to be elucidated. In this study, we established a mouse unilateral ureteral obstruction (UUO) model to investigate the expression of CA19-9 protein in renal tissue. To investigate the progression of hydronephrosis following UUO, MR urography and pathological analysis were performed. CA19-9 expression was examined by immunohistochemistry and western blot analysis. MR urography revealed that the grade of pelvic dilatation increased in a time dependent manner. Pathologically, both interstitial cellular infiltration and fibrosis were detected from the second to the fourteenth day after surgery in UUO mice. CA19-9 was detected in the UUO kidney after the second day. The immunoblot analysis revealed that the elevated expression of CA19-9 was demonstrated at an early stage of obstructive nephropathy. Our study shows that the ureteral obstructed kidney is dominated by cell infiltration and induced fibrosis. The selective expression of CA19-9 was detected in renal fibrous tissue. Based on these findings, the level of CA19-9 might be a good indicator for onset of renal fibrosis induced by obstruction

Immunohistochemical Analysis of Connexin43 Expression in Infertile Human Testes

Connexin43 (Cx43) is abundantly expressed in mammalian testes and implicated in the regulation of cell-to-cell interaction between germ cells and Sertoli cells, which is essential to the normal process of spermatogenesis. In the present study, we investigated the relation between Cx43 expression and the degree of spermatogenesis in infertile human testes. Immunohistochemical analysis of Cx43 was performed on testicular biopsies from 29 patients with azoospermia (n=23) and severe oligospermia (n=6), who gave informed consent to this experiment. The degree of testicular spermatogenesis was evaluated by Johnsen score. In the interstitium, immunostaining for Cx43 was localized to some focal parts of plasma membrane between neighboring Leydig cells. In seminiferous tubules with normal spermatogenesis, Cx43 expression was found between Sertoli cells and germ cells. However, Cx43 expression in maturation arrest was decreased and located mainly in the basal compartment of seminiferous tubules. Finally, there was a significant positive correlation between histological score of spermatogenesis and intensity of Cx43 (p=0.0294). These data suggest that the alteration of Cx43 expression may be involved in spermatogenic impairment, and that the communication between Sertoli cells and germ cells through Cx43 may be important for maturation of spermatogenesis

Coexpression of Keratinocyte Growth Factor and Its Receptor in Normal and Prostate Cancer Tissues: Possible Formation of Autonomous Andromedin Loop

Keratinocyte growth factor (KGF), an androgen-dependent epithelial mitogen, and its receptor (KGFR) have been implicated in the regulation of cell growth and differentiation in prostate tissue. This study was designed to determine the expression and role of KGF and KGFR in normal and prostate cancer tissues, especially in relation to cell kinetics. In 41 cases of prostate cancer in paraffin-embedded specimens, the expression of KGF and KGFR at the levels of protein and mRNA was analyzed by immunohistochemistry using newly raised antibodies and in situ hybridization, respectively. We also examined expression of androgen receptor (AR) and Ki-67 labeling index (LI). In normal and hyperplastic prostate tissues, both KGF mRNA and protein were localized in AR positive stromal cells, while those of KGFR were localized in glandular epithelial cells. In prostate cancer, however, coexpression of KGF and KGFR was observed in 14/41 cases, and significantly correlated with high Gleason scores, bone metastasis and high Ki-67 LI. The relapse-free survival of patients suffering from prostate cancers coexpressing KGF and KGFR was significantly shorter than that of patients from the other ones. Therefore, our results indicate that coexpression of KGF and KGFR in prostate cancer may predict metastatic and proliferative activities, possibly due to the formation of an autonomous andromedin loop

Coexpression of Keratinocyte Growth Factor and Its Receptor in Normal and Prostate Cancer Tissues: Possible Formation of Autonomous Andromedin Loop

Keratinocyte growth factor (KGF), an androgen-dependent epithelial mitogen, and its receptor (KGFR) have been implicated in the regulation of cell growth and differentiation in prostate tissue. This study was designed to determine the expression and role of KGF and KGFR in normal and prostate cancer tissues, especially in relation to cell kinetics. In 41 cases of prostate cancer in paraffin-embedded specimens, the expression of KGF and KGFR at the levels of protein and mRNA was analyzed by immunohistochemistry using newly raised antibodies and in situ hybridization, respectively. We also examined expression of androgen receptor (AR) and Ki-67 labeling index (LI). In normal and hyperplastic prostate tissues, both KGF mRNA and protein were localized in AR positive stromal cells, while those of KGFR were localized in glandular epithelial cells. In prostate cancer, however, coexpression of KGF and KGFR was observed in 14/41 cases, and significantly correlated with high Gleason scores, bone metastasis and high Ki-67 LI. The relapse-free survival of patients suffering from prostate cancers coexpressing KGF and KGFR was significantly shorter than that of patients from the other ones. Therefore, our results indicate that coexpression of KGF and KGFR in prostate cancer may predict metastatic and proliferative activities, possibly due to the formation of an autonomous andromedin loop

Altered tau isoform ratio caused by loss of FUS and SFPQ function leads to FTLD-like phenotypes

Fused in sarcoma (FUS) and splicing factor, prolineandglutamine-rich (SFPQ) are RNA binding proteinsthat regulate RNA metabolism. We found that alternativesplicing of the Mapt gene at exon 10, whichgenerates 4-repeat tau (4R-T) and 3-repeat tau(3R-T), is regulated by interactions between FUSand SFPQ in the nuclei of neurons. HippocampusspecificFUS- or SFPQ-knockdown mice exhibitfrontotemporal lobar degeneration (FTLD)-like behaviors,reduced adult neurogenesis, accumulationof phosphorylated tau, and hippocampal atrophywith neuronal loss through an increased 4R-T/3R-Tratio. Normalization of this increased ratio by 4R-Tspecificsilencing results in recovery of the normalphenotype. These findings suggest a biological linkamong FUS/SFPQ, tau isoform alteration, andphenotypic expression, which may function in theearly pathomechanism of FTLD