A chemically stable fluorescent marker of the ureter.

Surgical methods guided by exogenous fluorescent markers have the potential to define tissue types in real time. Small molecule dyes with efficient and selective renal clearance could enable visualization of the ureter during surgical procedures involving the abdomen and pelvis. These studies report the design and synthesis of a water soluble, net neutral C4'-O-alkyl heptamethine cyanine, Ureter-Label (UL)-766, with excellent properties for ureter visualization. This compound is accessed through a concise synthetic sequence involving an N- to O-transposition reaction that provides other inaccessible C4'-O-alkyl heptamethine cyanines. Unlike molecules containing a C4'-O-aryl substituent, which have also been used for ureter visualization, UL-766 is not reactive towards glutathione and the cellular proteome. In addition, rat models of abdominal surgery reveal that UL-766 undergoes efficient and nearly exclusive renal clearance in vivo. In total, this molecule represents a promising candidate for visualizing the ureter during a variety of surgical interventions.

[A Case of Renal Cell Carcinoma Growing into the Renal Pelvis with a Fibrin Cap in the Ureter and Bladder].

We present a case of renal cell carcinoma growing into the renal pelvis with a fibrin cap in the ureter and bladder. A 66-year-old man presented to our hospital with anemia and gross hematuria. Computed tomography showed a large left renal tumor and space-occupying lesions in the left renal pelvis and ureter. Cystoscopy showed a 2 cm-restiform mass protruding from the left ureteral orifice. We performed open left nephroureterectomy, and there was a 3 cm white mass with a smooth surface in the bladder. Pathological examination of the resected mass revealed clear cell carcinoma with urinary collecting system invasion and fibrin cap in the ureter and bladder. As a result, it would have been difficult to make the diagnossis of renal cell carcinoma preoperatively if we had performed biopsy of the mass in the bladder or ureter. The patient was diagnosed as having lung metastases 5 months after surgery. Urinary collecting system invasion has been considered an independent prognostic factor in pT3 renal cell carcinoma.

A proteomic glimpse into human ureter proteome.

Urine has evolved as one of the most important biofluids in clinical proteomics due to its noninvasive sampling and its stability. Yet, it is used in clinical diagnostics of several disorders by detecting changes in its components including urinary protein/polypeptide profile. Despite the fact that majority of proteins detected in urine are primarily originated from the urogenital (UG) tract, determining its precise source within the UG tract remains elusive. In this article, we performed a comprehensive analysis of ureter proteome to assemble the first unbiased ureter dataset. Next, we compared these data to urine, urinary exosome, and kidney mass spectrometric datasets. Our result concluded that among 2217 nonredundant ureter proteins, 751 protein candidates (33.8%) were detected in urine as urinary protein/polypeptide or exosomal protein. On the other hand, comparing ureter protein hits (48) that are not shown in corresponding databases to urinary bladder and prostate human protein atlas databases pinpointed 21 proteins that might be unique to ureter tissue. In conclusion, this finding offers future perspectives for possible identification of ureter disease-associated biomarkers such as ureter carcinoma. In addition, the ureter proteomic dataset published in this article will provide a valuable resource for researchers working in the field of urology and urine biomarker discovery. All MS data have been deposited in the ProteomeXchange with identifier PXD002620 (http://proteomecentral.proteomexchange.org/dataset/PXD002620).

Expression of VEGF in neonatal urinary obstruction: does expression of VEGF predict hydronephrosis?

BACKGROUND: In animal studies, the inhibition of VEGF activity results in high mortality and impaired renal and glomerular development. Mechanical stimuli, like mechanical stretch in respiratory and circulatory systems, results in an elevated expression of VEGF. In animal models, the experimental urinary obstruction is associated with stretching of tubular cells and activations of the renin-angiotensin system. This results in the upregulation of vascular endothelial growth factor (VEGF) and TNF-alfa. MATERIAL/METHODS: Tissue samples from urinary tract obstruction were collected and immunohistochemistry was performed in 14 patients (average age: 7.1±4.1 years). The control histology group consisted of ureteropelvic junction tissue from 10 fetuses after midtrimester artificial abortion. The fetuses did not have any failure at ultrasound screening and pathological examination. The mean gestational age was 20.6 weeks of gestation (±2.2SD). Expression of VEGF was detected with immunohistochemistry method. RESULTS: Expression of VEGF was found in varying intensity in the submucosa and subserosa layers, but only in the test tissue (placental tissue). The tissue of the patients with urinary obstruction and the tissue of the fetal ureteropelvic junction without urinary obstruction were negative for expression of VEGF. The repeated examination showed negative cells and no color staining. CONCLUSIONS: The pressure due to congenital urogenital obstruction resulting in mechanical stress in cells did not increase the expression of VEGF in young children in our study. To find a correlation between urogenital tract obstruction and increased expression of VEGF, we need to perform more examinations because the connection may be of therapeutic significance.

Automated Spectroscopic Tissue Classification in Colorectal Surgery.

BACKGROUND: In colorectal surgery, detecting ureters and mesenteric arteries is of utmost importance to prevent iatrogenic injury and to facilitate intraoperative decision making. A tool enabling ureter- and artery-specific image enhancement within (and possibly through) surrounding adipose tissue would facilitate this need, especially during laparoscopy. To evaluate the potential of hyperspectral imaging in colorectal surgery, we explored spectral tissue signatures using single-spot diffuse reflectance spectroscopy (DRS). As hyperspectral cameras with silicon (Si) and indium gallium arsenide (InGaAs) sensor chips are becoming available, we investigated spectral distinctive features for both sensor ranges. METHODS: In vivo wide-band (wavelength range 350-1830 nm) DRS was performed during open colorectal surgery. From the recorded spectra, 36 features were extracted at predefined wavelengths: 18 gradients and 18 amplitude differences. For classification of respectively ureter and artery in relation to surrounding adipose tissue, the best distinctive feature was selected using binary logistic regression for Si- and InGaAs-sensor spectral ranges separately. Classification performance was evaluated by leave-one-out cross-validation. RESULTS: In 10 consecutive patients, 253 spectra were recorded on 53 tissue sites (including colon, adipose tissue, muscle, artery, vein, ureter). Classification of ureter versus adipose tissue revealed accuracy of 100% for both Si range and InGaAs range. Classification of artery versus surrounding adipose tissue revealed accuracies of 95% (Si) and 89% (InGaAs). CONCLUSIONS: Intraoperative DRS showed that Si and InGaAs sensors are equally suited for automated classification of ureter versus surrounding adipose tissue. Si sensors seem better suited for classifying artery versus mesenteric adipose tissue. Progress toward hyperspectral imaging within this field is promising.

Distribution of cocaine and amphetamine regulated transcript in ureters and urinary bladder of hypertensive rats.

Cocaine and amphetamine regulated transcript (CART), a neuropeptide of the central and peripheral nervous system plays an essential role in maintaining body homeostasis by regulating body temperature, orexia, digestive motility and blood pressure. Very few studies describe the relationship of hyperten¬sion with CART. Therefore, the present research was undertaken to identify, locate and determine the number of CART-immunopositive neuroendocrine cells (NE) and structures in the urinary bladder and ureter of rats with experimentally induced nephrogenic hypertension. The experiments were conducted on 20 Wistar rats in which hypertension was experimentally induced by applying a clamp on the left renal artery based on the two kidney, one clip experimental model (2K1C). After 6 weeks, fragments of the ureters and urinary bladder were sampled from rats with permanent hypertension. Immunohisto¬chemical analyses revealed a salient effect of renovascular hypertension on the neuroendocrine system of rat ureters and urinary bladder. Differences in the number of neuroendocrine cells and in the density of CART-positive structures were identified between the hypertensive and normotensive (control) rats. Hypertension greatly increased the number of NE cells and the density of CART- immunoreactive (IR) structures in the analysed urinary system organs.

Novel biocatalytic polymer-based antimicrobial coatings as potential ureteral biomaterial: preparation and in vitro performance evaluation.

Catheters and other indwelling devices placed inside human body are prone to bacterial infection, causing serious risk to patients. Infections associated with implants are difficult to resolve, and hence the prevention of bacterial colonization of such surfaces is quite appropriate. In this context, the development of novel antimicrobial biomaterials is currently gaining momentum. We describe here the preparation and antibacterial properties of an enzyme-embedded polycaprolactone (PCL)-based coating, coimpregnated with the antibiotic gentamicin sulfate (GS). The enzyme uses PCL itself as substrate; as a result, the antibiotic gets released at a rate controlled by the degradation of the PCL base. In vitro drug release studies demonstrated sustained release of GS from the PCL film throughout its lifetime. By modulating the enzyme concentration in the PCL film, we were able to vary the lifetime of the coating from 33 h to 16 days. In the end, the polymer is completely degraded, delivering the entire load of the antibiotic. The polymer exhibited antibacterial properties against three test isolates: Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Foley urinary catheters coated with the modified polymer exhibited sustained in vitro release of GS over a 60-h period. The results suggest that the antibiotic-plus-enzyme-loaded polymer can be used as tunable self-degrading antimicrobial biomaterial coating on catheters.

Surface analysis of ureteral stent before and after implantation in the bodies of child patients.

The aim of this work was to determine which part of a double-J ureteral stent (DJ stents) showed the highest tendency to crystal, calculi, and biofilm deposition after ureterorenoscopic-lithotripsy procedure (URS-L) to treat calcium oxalate stones. Additionally, the mechanical strength and the stiffness of DJ stents were evaluated before and after exposure to urine. Obtained results indicated that the proximal (renal pelvis) and distal (urinary bladder) part is the most susceptible for post-URS-L fragments and urea salt deposition. Both, the outer and inner surfaces of the DJ ureteral stents were completely covered even after 7 days of implantation. Encrustation of DJ stents during a 31-day period results in reducing the Young's modulus by 27-30%, which confirms the loss of DJ stent elasticity and increased probability of cracks or interruption. Performed analysis pointed to the need to use an antibacterial coating in the above-mentioned part of the ureteral stent to prolong its usage time and to prevent urinary tract infection.

Altered anoctamin-1 and tyrosine phosphorylation in congenital ureteropelvic junction obstruction.

PURPOSE: Ureteropelvic junction (UPJ) obstruction is the most common cause of congenital hydronephrosis in children. The pathophysiology of UPJ obstruction and the exact mechanism of pelviureteral peristalsis are poorly understood. Anoctamin-1 (ANO1), a Ca2+-activated chloride channel, has been shown to play a key role in muscle wall contractions in the gastrointestinal tract. We designed this study to investigate the hypothesis that ANO1 is expressed in smooth muscle cells (SMCs) of the human UPJ and that tyrosine phosphorylation is altered in UPJ obstruction. MATERIALS AND METHODS: Fresh frozen specimens of UPJ obstruction (n = 28) and control specimens from patients who underwent Wilms' tumor nephrectomy (n = 20) were prepared. Western blot (WB) was performed to evaluate levels of ANO1 protein expression and changes in tyrosine phosphorylation. In addition analysis of ANO1 and phalloidin using confocal-immunofluoresence-double staining and 3D reconstruction were carried out. RESULTS: Our WB results revealed increased tyrosine phosphorylation in UPJ obstruction samples compared to controls, and decreased ANO1 expression in UPJ obstruction. Confocal microscopy showed that ANO1 immunoreactivity was decreased in SMCs of UPJ obstruction compared to controls. CONCLUSIONS: We provide evidence, for the first time, of the presence of ANO1 expression in the human UPJ. We speculate that altered tyrosine phosphorylation, observed in UPJ obstruction, may lead to a failure of transmission of peristaltic waves in UPJ obstruction by inhibiting Ca2+-activated chloride channels in SMCs.

Contrasting expression patterns of three members of the myc family of protooncogenes in the developing and adult mouse kidney.

The myc family of protooncogenes encode similar but distinct nuclear proteins. Since N-myc, c-myc, and L-myc have been found to be expressed in the newborn kidney, we studied their expression during murine kidney development. By organ culture studies and in situ hybridization of tissue sections, we found that each of the three members of the myc gene family shows a remarkably distinct expression pattern during kidney development. It is known that mesenchymal stem cells of the embryonic kidney convert into epithelium if properly induced. We demonstrate the N-myc expression increases during the first 24 h of in vitro culture as an early response to induction. Moreover, the upregulation was transient and expression levels were already low during the first stages of overt epithelial cell polarization. In contrast, neither c-myc nor L-myc were upregulated by induction of epithelial differentiation. c-myc was expressed in the uninduced mesenchyme but subsequently became restricted to the newly formed epithelium and was not expressed in the surrounding loose mesenchyme. At onset of terminal differentiation c-myc expression was turned off also from the epithelial tubules. We conclude that N-myc is a marker for induction and early epithelial differentiation states. That the undifferentiated mesenchyme, unlike stromal cells of later developmental stages, express c-myc demonstrates that the undifferentiated mesenchymal stem cells are distinct from the stromal cells. The most astonishing finding, however, was the high level of L-myc mRNA in the ureter, ureter-derived renal pelvis, papilla, and collecting ducts. In the ureter, expression increased, rather than decreased, with advancing maturation and was highest in adult tissue. Our results suggest that each of the three members of the myc gene family are involved in quite disparate differentiation processes, even within one tissue.

Immuno-localization of CD44 and osteopontin in developing human kidney.

CD44 is observed in ureteric bud structures and is implicated in branching morphogenesis during early mouse renal development. Healthy adult kidney demonstrates minimal CD44, but CD44 is up-regulated in renal diseases. CD44 may mediate binding of calcium oxalate crystals to tubular epithelia via the ligands osteopontin (OPN) and hyaluronan. Because 15% of premature infants develop nephrocalcinosis, developmental tubular CD44 expression might promote nephrocalcinosis. We studied CD44 and OPN immuno-localization in developing human kidney by immunohistochemical analysis. Human renal tissue between 18 and 40 wk of gestation showed CD44 immuno-localization in ureteric buds, with staining decreasing with increasing gestational age; CD44 was rarely observed in developing renal tubules. OPN was diffusely observed in proximal tubules, rarely observed in distal tubules, ureteric buds or metanephric structures. These data support the role of CD44 in early human nephron formation and branching morphogenesis. Rare CD44 staining in developing tubular epithelium suggests no role for CD44 in promoting calcium oxalate adherence to tubular epithelia in premature infants. Immuno-localization of OPN in tubules supports its role in tubular differentiation, but OPN does not seem to be necessary during early nephron formation.

H-Ras, R-Ras, and TC21 differentially regulate ureteric bud cell branching morphogenesis.

The collecting system of the kidney, derived from the ureteric bud (UB), undergoes repetitive bifid branching events during early development followed by a phase of tubular growth and elongation. Although members of the Ras GTPase family control cell growth, differentiation, proliferation, and migration, their role in development of the collecting system of the kidney is unexplored. In this study, we demonstrate that members of the R-Ras family of proteins, R-Ras and TC21, are expressed in the murine collecting system at E13.5, whereas H-Ras is only detected at day E17.5. Using murine UB cells expressing activated H-Ras, R-Ras, and TC21, we demonstrate that R-Ras-expressing cells show increased branching morphogenesis and cell growth, TC21-expressing cells branch excessively but lose their ability to migrate, whereas H-Ras-expressing cells migrated the most and formed long unbranched tubules. These differences in branching morphogenesis are mediated by differential regulation/activation of the Rho family of GTPases and mitogen-activated protein kinases. Because most branching of the UB occurs early in development, it is conceivable that R-Ras and TC-21 play a role in facilitating branching and growth in early UB development, whereas H-Ras might favor cell migration and elongation of tubules, events that occur later in development.

Pathological changes in ureterovesical and ureteropelvic junction obstruction explained by fetal ureter histology.

The etiology of ureterovesical junction obstruction (UVJO) and ureteropelvic junction obstruction (UPJO) is obscure with an adynamic narrow segment causing the obstruction. In this study, the authors compared interstitial cells of Cajal (ICC) and collagen-to-muscle ratio (CM ratio) between UVJO, UPJO, and fetal ureters to investigate whether a maturational arrest of the fetal ureter could explain both clinical pathologies. METHODS: Group 1 (control) involved specimens of the normal ureter (nephrectomy for trauma/tumor; n = 20), while group 2, specimens of UVJO (n = 14); group 2 was further divided into group 2a, the dilated megaureter above UVJO, and group 2b, UVJO narrow segment; group 3, UPJO narrow segment excised during pyeloplasty (n = 31); and group 4, normal fetal ureters (n = 12). The specimens were analyzed for ICC using immunohistochemistry and CM ratio on Masson's trichrome (stains collagen in blue and muscle in red). RESULTS: The median ICC/10 high-power field was 16.1 (8.3) in the normal and 17.3 (7.9) in the dilated segment of the megaureter, with no significant difference, but was significantly less in the narrow segment of UVJO at 4.5 (2.0), narrow segment of UPJO at 5.1 (2.3), and fetal ureter at 5.0 (2.3). The median CM ratio was 0.75 (0.29) in the normal and 0.65 (0.2) in the dilated segment of the megaureter, with no significant difference between them (figure), but was significantly higher in the narrow segment of UVJO at 3.0 (0.8), narrow segment of UPJO at 2.5 (0.71), and fetal ureter at 3.1 (0.61). Overall UVJO, UPJO, and fetal ureter segment had significantly less ICC density and more collagen compared with the normal ureter (P < 0.001 by Mann-Whitney U test). DISCUSSION: There are conflicting reports on the etiopathogenesis of UVJO and UPJO, with several authors showing decreased ICC and increased collagen in the narrow segment. In this study, the authors found that the pathological changes at UVJ and UPJ segments resemble fetal ureter morphology. We also found that in fetal ureters, as the gestation progressed, there was an increase in the ICC density/smooth muscle, whereas the collagen content decreased. While the entire ureter has uniform embryological origin, it essentially remains an epithelial tube until the late gestation. The maturational process involves differentiation of smooth muscles cells/ICC to establish the peristaltic machinery required to functionally connect the ureter at both ends. This process, probably, starts at the mid ureter during fetal life and extends toward the UPJ and UVJ, and its failure, probably, results in UPJO or UVJO. The study's limitations are small numbers, and further larger studies are required to validate this hypothesis.

The molecular phenotypes of ureteral telocytes are layer-specific.

Telocytes (TC) are the delicate interstitial (stromal) cells defined by their long, thin and moniliform processes termed telopodes. Numerous studies determined that different subsets of telocytes populate almost all tissues and attempted to relate these subsets to various functions, from cell signaling to tissue repair and regeneration. Extremely few studies addressed the urinary tract though few data on the molecular pattern of the urinary TCs actually exist. We therefore hypothesized that subsets of urinary TCs co-localize within the human ureter and we aimed at performing an immunohistochemical study to evaluate the tissue-specific molecular pattern of TCs. On sample tissues of proximal ureter drawn from ten human adult patients during surgery were applied primary antibodies against CD34, CD105, von Willebrand Factor, the heavy chain of smooth muscle myosin (SMM) and c-erbB-2. The molecular pattern indicated three different subsets of ureteral TCs which are neither endothelial nor epithelial in nature: (a) type I: the CD34-/CD105+ TCs of the superficial layer of lamina propria; (b) type II: the CD34+/CD105± myoid TCs of the deep layer of lamina propria and (c) type III: the CD34+/CD105+ perivascular TCs. Although apparently different, all these subsets of TCs could belong to the stem/progenitor niche of the ureter.

Immersed multilayer biodegradable ureteral stent with reformed biodegradation: An in vitro experiment.

Objective The aim of this study was to develop a novel immersed multilayer biodegradable ureteral stent with reformed biodegradation and evaluate it in vitro. Methods Poly(glycolic-co-lactic acid) (PGLA), microsphere zein and BaSO4 were employed to produce a multilayer biodegradable stent using immersion technology. Tests of the biodegradable stents and conventional control stents were conducted in human urine in vitro to evaluate the biodegradable properties. The biocompatibility was assessed by the morphology and proliferation of urine-derived cells cultured with extracted media from the biodegradable stent and a latex material positive control. Results An immersed multilayer biodegradable stent was successfully produced. It began to degrade in week 2 and was fully degraded by week 4. The mass loss ratio in the first 2 weeks was low (approximately 10.0% at 1 week, 20.0% at 2 weeks) and increased after 3 weeks (approximately 70%) to the end of testing. During the first 2 weeks, the radial compression load performances of the biodegradable stents were better than those of the control stents with statistically significant differences ( p = 0.00, p = 0.01) and the tensile strengths were lower in the biodegradable stents than those in the control stents throughout the experiment. SEM showed that the stents degraded layer by layer from the outer to the inner wall. The influences on the cells of extracted medium from the biodegradable stents were morphologically slight and lower than 10% in relative growth rates. Conclusions This preliminary study demonstrates that the immersed multilayer biodegradable ureteral stent has good radial compression and biocompatible performance and can be degraded in vitro within 4 weeks in a moderate manner.

Comprehensive Genomic Characterization of Upper Tract Urothelial Carcinoma.

BACKGROUND: Upper urinary tract urothelial cancer (UTUC) may have unique etiologic and genomic factors compared to bladder cancer. OBJECTIVE: To characterize the genomic landscape of UTUC and provide insights into its biology using comprehensive integrated genomic analyses. DESIGN, SETTING, AND PARTICIPANTS: We collected 31 untreated snap-frozen UTUC samples from two institutions and carried out whole-exome sequencing (WES) of DNA, RNA sequencing (RNAseq), and protein analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adjusting for batch effects, consensus mutation calls from independent pipelines identified DNA mutations, gene expression clusters using unsupervised consensus hierarchical clustering (UCHC), and protein expression levels that were correlated with relevant clinical variables, The Cancer Genome Atlas, and other published data. RESULTS AND LIMITATIONS: WES identified mutations in FGFR3 (74.1%; 92% low-grade, 60% high-grade), KMT2D (44.4%), PIK3CA (25.9%), and TP53 (22.2%). APOBEC and CpG were the most common mutational signatures. UCHC of RNAseq data segregated samples into four molecular subtypes with the following characteristics. Cluster 1: no PIK3CA mutations, nonsmokers, high-grade

[Reactive transformation of human urinary smooth muscular tissue in some diseases (structural-metabolic aspects of organization)].

Smooth muscular tissue (SMT) of human urinary system was studied at different levels (renal pelvis, proximal and distal parts of the ureter) in health and some urological diseases (vesicoureteral reflux, ureteral obstruction). The method of target cell dissociation was used. The volume of myocytes, nuclei, nuclear-cytoplasmic correlation were calculated. Content of DNA and cytoplasmic protein was studied cytospectrophotometrically. Electron-microscopic study was also made. Three types of myocytes with different structural-metabolic parameters were detected. There were significant differences in mean volumes of myocytes, cytophotometric indices of SMT in different parts of the urinary tracts related to the pattern of these zones functioning. A comparative analysis of intact and affected SMT of the distal ureter demonstrated changes in the structure of leiomyocytes population, optic density of cytoplasmic protein and proliferative activity of myocytes which correlated depending on the kind and change of functional load.

Different adhesion and migration properties of human HCV29 non-malignant urothelial and T24 bladder cancer cells: role of glycosylation.

In tumour cells, alterations in cellular glycosylation may play a key role in their metastatic behaviour. This study used cell lines having very different behaviour in vivo: HCV29 non-malignant transitional epithelium and T24 bladder transitional cell carcinoma. These differences in behaviour might be due in part to differences in cellular glycosylation patterns. Glycan chain analysis of their glycoproteins was performed with the use of specific lectins. The functional role of carbohydrates was studied by treating these cells with swainsonine, an inhibitor of Golgi alpha-mannosidase II, and in vitro adhesion and migration assays. The adhesion of swainsonine-treated HCV29 and T24 cells was increased on fibronectin and type IV collagen by 1.5- and 2-fold, respectively, whereas adhesion on laminin was virtually unchanged after swainsonine-treatment in HCV29 cells and was increased in T24 cells. Swainsonine treatment reduced the rate of T24 cell migration by 20%. We concluded that beta1-6 branched tri- and tetraantennary complex-type glycans have an important function in adhesion and migration in the studied cell lines. These data support the view that oligosaccharides are involved in several steps of the metastatic process.

Expression of the hMLH1 and hMSH2 proteins in normal tissues: relationship to cancer predisposition in hereditary non-polyposis colon cancer.

The majority of tumours in patients with hereditary non-polyposis colon cancer (HNPCC) occur in large intestine and endometrium; also, other tissues are at increased risk. We studied expression of hMLH1 and hMSH2 proteins in 148 normal samples of various tissues from non-HNPCC patients and in 14 normal colon tissues from HNPCC patients. Immunohistochemical technique was used. Intensity of nuclear staining, percentage of stained cells and H-scores were calculated. Tissues were divided into groups. Groups A, B and C included tissues with increased risk of cancer in HNPCC A) stomach, small and large bowel; (B) endometrium; (C) ovary, ureter, urinary bladder, kidney and liver. Group D tissues were without increased risk. Expression of the proteins was significantly higher in groups A, B and C compared with group D (P<0.0001, P=0.0004 for hMSH2 in C versus D). The expression was highest in testis. In colons of HNPCC patients, expression of the mutated gene product was significantly lower than in non-HNPCC patients. In conclusion, hMLH1/hMSH2 protein expression is constitutively higher in certain cell types of certain tissues, including the majority of tissues that are at increased risk of cancer in HNPCC. However, association of strong hMLH1/hMSH2 expression with cancer risk is not strictly valid.

Characterization of nanostructured ureteral stent with gradient degradation in a porcine model.

A tubular poly(ε-caprolactone) (PCL)/poly(lactide-co-glycolide) (PLGA) ureteral stent composed of nanofibers with micropores was fabricated by double-needle electrospinning. The stent was ureteroscopically inserted into six Changbai pigs, and the commercial polyurethane Shagong(®) stent was inserted into four pigs as control. Intravenous pyelography revealed that the PCL/PLGA stent gradually degraded from the distal end to proximal terminal, and all stents were completely degraded at 10 weeks post-insertion. No significant difference was observed in hydronephrosis severity between the two groups. The levels of serum creatinine and urine pH remained similar throughout the study in the two groups, but the number of white blood cells in the urine was significantly higher in the Shagong(®) stent group. On Day 70, histological evaluation indicated equivalent histological severity scores in the middle and distal ureter sections and bladder in the two groups. However, the PCL/PLGA stent-implanted pigs had significantly lower mean severity scores in the kidney and proximal ureter sites. These data revealed that the PCL/PLGA stent degraded in a controlled manner, did not induce obstruction, and had a lower urothelial impact in comparison to the Shagong(®) stent, indicating that the stent exhibited great potential for clinical application.