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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the distribution and density of epidermal growth factor (EGF) receptors (EGF-Rs) on urothelium, immunohistological studies using a monoclonal antibody to the binding portion of the human EGF-R were performed on frozen specimens of normal urothelium (N = 20), urothelium from patients with nonurothelial urological malignancies (N = 15) and inflammatory diseases (N = 8), low grade superficial transitional cell carcinomas (TCC) (N = 13), high grade superficial or invasive TCC (N = 28), and endoscopically normal appearing urothelium from patients with low grade superficial (N = 5) or high grade (N = 21) TCC elsewhere in the bladder (or ipsilateral renal pelvis/ureter). EGF-Rs are found only on the basal layer of epithelial cells (with scattered representation on intermediate cells) in 95% of normal urothelial specimens and 100% of pathological specimens without urothelial malignancy. Alternatively, 92.3% of specimens of low grade superficial TCC and 100% of high grade TCCs had EGF-Rs richly expressed on the superficial as well as the deeper layers of urothelium. This "malignant" distribution of EGF-Rs was also found on all specimens of endoscopically normal appearing urothelium in patients with TCC elsewhere. The density of EGF-Rs correlated closely with tumor grade on both "premalignant" and frankly neoplastic urothelium. We conclude that the expression of EGF-Rs on urothelium favors the interaction of premalignant and malignant tissue with urinary EGF. To determine if altering the physiochemical environment of urine could interfere with this interaction, the effects of pH on the binding of and growth responses to EGF were assessed on four human TCC cell lines. Scatchard plots demonstrated that varying pH from 5.0 to 7.5 did not significantly change the total number of receptors, but EGF-R affinity was reduced approximately 20-fold as pH decreased from 7.5 to 5 in each TCC target. Similarly, significant growth stimulation by EGF at pH 7.5 was abrogated at pH less than or equal to 7.0 while growth rates in the absence of EGF remained unchanged at lower pHs. It thus appears that urinary acidification may hold promise in the management and prevention of recurrent bladder cancer.
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PMID:Clinical implications of the expression of epidermal growth factor receptors in human transitional cell carcinoma. 169 May 99

Differentiation of the metanephrogenic mesenchyme is triggered by an inductive tissue interaction between an inducer tissue and the mesenchyme. It is generally believed that the epithelial ureter bud acts as an inducer during in vivo development. In response to the inductive stimulus most of the mesenchymal cells convert into epithelial cells, while a small fraction differentiates into stromal cells. In vitro, differentiation of isolated mesenchyme to epithelium can be induced by a variety of embryonic tissues, but nothing is known about the molecular nature of the inducing stimulus. In recent years, large numbers of polypeptide growth factors have been described, which in addition to proliferative effects were shown to exert effects on a variety of biological phenomena such as chemotaxis, inflammation, tissue repair, or induction of embryonic development. We therefore analyzed whether growth factors in the absence of inducer tissue can induce isolated kidney mesenchyme to differentiate into epithelium or interstitium. As expected, both growth and differentiation into epithelium were stimulated by an inducer tissue, the spinal cord. We found that none of the various growth factors tested (including epidermal growth factor, transforming growth factors alpha and beta, insulin-like growth factors I and II, fibroblast growth factor, platelet-derived growth factor, and retinoic acid) could mimick the effect of an inducer tissue, although we tested the factors over a wide concentration range. One of the tested factors, epidermal growth factor (EGF) stimulated the mesenchymal cells to become stromal cells, although it could not stimulate development into epithelium. EGF could stimulate stromal development both when the mesenchyme was cultured in isolation and when the mesenchyme was stimulated by an inducer tissue to become epithelium. The expansion of the stromal compartment in response to EGF treatment occurred at the expense of the epithelial cells, but EGF could not completely suppress the formation of epithelium. These data suggest the presence of EGF receptors in the developing kidney, but since application of soluble EGF leads to abnormal development, soluble EGF cannot be the natural ligand. We suggest that locally produced mitogens with an EGF-like structure may regulate the relative amounts of stroma (interstitium) and epithelium in the developing kidney.
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PMID:Development and growth of mouse embryonic kidney in organ culture and modulation of development by soluble growth factor. 201 31

We measured epidermal growth factor (EGF) in the urine of 54 untreated patients with malignant tumors (7 prostatic cancer, 11 renal tumor, 31 bladder cancer, 3 renal pelvic tumor, 2 ureter tumor) in the Toyama Medical & Pharmaceutical University Hospital. We also measured EGF in the urine of 77 normal subjects (43 males, 34 females). Urinary concentration of EGF in normal subjects decreased with increasing age. It was significantly higher in females than males (p less than 0.05). Urinary concentration of EGF in patients with prostatic cancer or renal tumor was similar to that in normal subjects. The patients with prostatic cancer controlled by estrogen showed a slightly high level of EGF in the urine. In patients with renal tumor, urinary concentration of EGF decreased after nephrectomy. Patients with bladder cancer showed a significant decrease of EGF in the urine compared with normal subjects (p less than 0.05), and urinary concentration of EGF in the patients with bladder cancer of high stage was remarkably low. Low concentration of EGF in the urine was recognized in patients with renal pelvic tumor or ureter tumor. However, the relationship between the decrease of urinary concentration of EGF in these urothelial tumors and the growth of these tumors remains to be elucidated.
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PMID:[Clinical study of epidermal growth factor in the urine of the patients with urological malignant tumor]. 205 97

Antigenic characterization of urothelial cells cultured from normal adult ureter was performed. These cells were cultured using a simplified isolation and culture technique and a commercially available serum-free medium. The cells growing in these cultures had epithelioid morphology and normal quantities of DNA. The antigen expression on these cultured normal urothelial cells was evaluated using a panel of monoclonal antibodies: 5G6.4, AN43, URO-5, anti-keratin and anti-blood group antibodies, and 425 (anti-epidermal growth factor receptor). Lower levels of anti-A and AN43 binding on cultured cells were observed than are seen on urothelial cells in sections of normal ureter, while the binding of anti-blood group H, 5G6.4, and URO-5 was unchanged. Binding of anti-epidermal growth factor receptor antibody 425 was improved if the cells were grown in medium lacking epidermal growth factor. These results confirm the urothelial origin of these cultured urothelial cells but indicate that some antigenic differences between cultured normal urothelial cells and urothelial cells in situ in the normal ureter exist.
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PMID:Comparison of antigen expression on normal urothelial cells in tissue section and tissue culture. 223 15

The potent toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is teratogenic in mice, producing hydronephrosis and cleft palate. Because of the long half-life of TCDD, the urinary tract is exposed throughout development after a single dose on gestation day (GD) 10 or earlier. TCDD-induced hydronephrosis is a consequence of occlusion of the ureter by epithelial cells. Since embryonic growth factors and the epidermal growth factor (EGF) receptor are probably involved in regulation of embryonic cell proliferation, this study examines the effects of TCDD on expression of EGF receptors and proliferation of ureteric epithelial cells in vivo and in culture. After exposure to TCDD by gavage (12, 24, or 30 micrograms/kg on GD 10; 6 or 24 micrograms/kg on GD 12) the mean cell depth of the ureteric and bladder epithelia was increased. EGF receptors were detected immunohistochemically in sectioned urinary tracts. The expression of receptors decreased with advancing development in control ureteric epithelia. However, after TCDD exposure the level of EGF receptors failed to decline. The incorporation of 3H-TdR was observed in sections by autoradiography, and after exposure to TCDD more epithelial cells showed incorporation than was apparent in controls. Transmission electron microscopy (TEM) of embryonic ureters from fetuses exposed to TCDD in vivo showed no cytotoxicity in basal cells and the cells remained undifferentiated, as in controls. Ureters taken from GD 12 embryos and cultured with 1 x 10(-10)M TCDD showed ureteric epithelial hyperplasia without cytotoxicity, but at 1 x 10(-8)M TCDD evidence of cytotoxicity was observed by TEM. The levels of TCDD found in fetuses after in vivo exposure (204-307 pg/fetus, with 1-2 pg in the urinary tract) compare well with the in vitro level (32 pg/ml), which was most effective in producing hyperplasia of the epithelial cells. The present study correlates a TCDD-induced increase in cell depth with altered regulation of EGF receptors and excessive proliferation, both in vivo and in cultured embryonic ureters.
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PMID:Effects of TCDD on embryonic ureteric epithelial EGF receptor expression and cell proliferation. 230 75

We have recently discovered that prolonged systemic administration of epidermal growth factor (EGF) induces a remarkable growth of all wall layers of the urinary tract in minipigs. In the present paper, we report the most pronounced changes induced by 4 weeks of systemic EGF challenge in two pigs treated for four weeks with either solvent or EGF (30 micrograms/kg/day), respectively. The EGF treated ureter was longer and thicker with an approximately four fold increase in diameter. All wall layers were enlarged. The urothelium was increased from 5 to 10 cellular rows with basal hyperplasia and an increased number of goblet cells and cells with intracytoplasmic lumina in the luminal half. In the muscular coat, the bundles of hypertrophied cells and intervening connective tissue were enlarged. The present paper suggests a possible in vivo approach to increase the amount of tissue needed in reconstructive surgery of the urinary tract.
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PMID:Ureteric growth in a Goettingen minipig induced by epidermal growth factor. A case report. 857 47

The expression of cripto, a novel transforming gene of the epidermal growth factor superfamily, was immunohistochemically examined in 20 cases of urinary bladder, one ureter, three renal pelvic, 18 kidney, nine prostate, three adrenal and four testicular tumors. Three cases of urinary bladder carcinomas, two of grade 2 and one of grade 3 transitional cell carcinoma which were T1a and T3b, and INF beta and INF gamma, respectively, showed positive binding of specific antibody, along with one cortical carcinoma of the adrenal gland positive staining. None of the ureter, renal pelvic, kidney, prostate or testicular tumors showed positive staining. These results indicate that cripto is not frequently expressed in urological tumors.
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PMID:Cripto expression in human urological tumors. 902 29

Prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces hydronephrosis in C57BL/6N mice. The etiology of this response involves TCDD-induced hyperplasia of ureteric epithelium, which occludes the ureteric lumen, blocking the flow of urine. The present study localizes and examines the effects of TCDD on the expression of the Ah receptor (AhR), the Ah receptor nuclear translocator (ARNT), epidermal growth factor (EGF), and transforming growth factor-alpha (TGF-alpha) in the epithelial cells of the developing urinary tract, particularly the ureteric bud derivatives (ureter and tubules). Pregnant C57BL/6N mice were dosed on gestation day (GD) 10 with either corn oil or TCDD at 12 micrograms/kg; a dose of 24 micrograms/kg is expected to induce 100% hydronephrosis. The metanephric urinary tract is morphologically detectable as early as GD 12; thus, embryos were removed on GD 12, 13, and 14, and the lower dorsal torso was prepared for immunohistochemistry or in situ hybridization. Regardless of treatment, the expression of both AhR and ARNT increased in epithelial cells of the ureter and AhR increased in the metanephric tubules from GD 12-14. In situ hybridization localized the expression of AhR and ARNT mRNAs to these derivatives of the ureteric bud and levels of mRNA increased throughout the developmental period examined. There were no significant effects of TCDD treatment on expression of AhR, while TCDD significantly decreased levels of ARNT in tubules on GD 14. The epithelial cells of the ureter and tubules expressed TGF-alpha and EGF. EGF increased from GD 12 to 13 in the tubules and ureter, but there was no difference from GD 13 to 14. Treatment with TCDD reduced TGF-alpha significantly only in tubules on GD 13. TCDD exposure significantly decreased EGF in ureter and tubule cells on both GD 13 and 14. In summary, the epithelial cells of the embryonic mouse urinary tract expressed AhR, ARNT, EGF, and TGF-alpha in developmentally dependent patterns. These proteins are involved in the regulation of embryonic cell proliferation during normal urinary tract development and are probably involved in the hyperplastic response to TCDD.
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PMID:Effects of TCDD on Ah receptor, ARNT, EGF, and TGF-alpha expression in embryonic mouse urinary tract. 926 27

Systemic treatment with epidermal growth factor (EGF) induces growth of all wall layers of the urinary tract in pigs and rats. In this study, we describe the time-dependent growth of the ureter and bladder. Forty-eight female Wistar rats were allocated into five groups receiving EGF treatment (150 microg/kg per day) for 0 (controls), 1, 2, 3 or 4 weeks before being killed. The 24-h urine excretion was increased only in the group treated for 4 weeks with EGF. Measured by a simple infusion device, EGF significantly increased the bladder capacity by more than 50% in all the EGF-treated groups. The volumes of the wall layers of the ureter and bladder were quantified using stereology. After 4 weeks of treatment with EGF, the total volumes of the ureter and bladder were 1.8- and 2.1-fold larger than in the control group (the urothelium was 2.8- and 3.5-fold larger and the muscular coat 1.6- and 1.6-fold larger in the ureter and bladder, respectively). In conclusion, the EGF-induced growth of the urinary tract is characterized by increased bladder capacity, and increased volume of all wall layers --most prominently the urothelium.
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PMID:The effects of exogenous epidermal growth factor on the developing urinary tract in rats: a stereological description. 963 42

Distinct patterns of cell proliferation and apoptosis have been recognized for tubular, interstitial, and glomerular cells in chronic obstructive uropathy (OU). In many experimental models of OU, tubular cell apoptosis develops quickly after ureter ligation, peaks between 7 and 24 days postobtruction (about 30-fold of control), and tapers thereafter. Apoptosis initially involves the dilated collecting ducts, but subsequently spreads to other tubules. Tubular cell apoptosis probably accounts for renal tissue loss in OU because a direct correlation between its degree and the decline in dry kidney weight is well-documented. Pronounced tubular cell proliferation occurs shortly after ureter ligation, peaks at about day 6 (60-fold above control), and quickly subsides to baseline. Because the peak of tubular cell proliferation immediately precedes the onset of tubular cell apoptosis, a pathogenetic link may exist between these two processes. Interstitial cell apoptosis occurs with an increasing frequency throughout the course of OU (up to 35-fold above control). Interstitial cell proliferation appears in a bimodal pattern with the early peak coinciding with that of tubular cell proliferation and consisting mostly of fibroblasts, whereas the later peak consists mostly of inflammatory cells. Glomerular cell apoptosis and proliferation are not different from control, which explains, in part, the structural integrity of the glomeruli throughout the disease course. Although the general pathways of cell apoptosis and proliferation are well known, the molecular control of these processes in OU is poorly understood. In addition, whether apoptosis or proliferation of tubular and interstitial cells is differentially regulated remains to be studied. However, several molecules known to be activated or overexpressed in kidney with OU may modulate cell apoptosis and proliferation. The relevant functions of these molecules include induction of apoptosis (angiotensin II, reactive oxygen species, jun-N-terminal kinase, p53), inhibition of the cell cycle (transforming growth factor-beta, p21), inhibition of apoptosis (clusterin, epidermal growth factor, insulin-like growth factor, bcl-2, osteopontin), or promotion of interstitial fibroblast proliferation (platelet-derived growth factor).
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PMID:Cell apoptosis and proliferation in obstructive uropathy. 981 55


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