Urinary Bladder Transitional Cell Research Articles

Anti-tumor activity of a recombinant measles virus against canine lung cancer cells

Canine primary lung cancer with metastasis has a poor prognosis with no effective treatment. We previously generated a recombinant measles virus (MV) that lost binding affinity to a principal receptor, SLAM, to eliminate its virulence as a new cancer treatment strategy. The virus, rMV-SLAMblind, targets nectin-4, recently listed as a tumor marker, and exerts antitumor activity against nectin-4-positive canine mammary cancer and urinary bladder transitional cell carcinoma cells. However, the effectivity of rMV-SLAMblind for other types of canine cancers is still unknown. Here we evaluated the antitumor effect of rMV-SLAMblind to canine lung cancer. Nectin-4 is expressed on three canine lung cancer cell lines (CLAC, AZACL1, AZACL2) and rMV-SLAMblind was able to infect these cell lines. CLAC cells showed reduced cell viability after virus infection. In the CLAC xenograft nude mouse model, intratumoral administration of rMV-SLAMblind significantly suppressed tumor growth. In rMV-SLAMblind-treated mice, natural killer cells were activated, and Cxcl10 and Il12a levels were significantly increased in comparison with levels in the control group. In addition, the depletion of NK cells reduced the anti-tumor effect. To understand difference in efficacy among canine lung cancer cell lines, we compared virus growth and gene expression pattern after virus treatment in the three canine lung cancer cell lines; virus growth was highest in CLAC cells compared with the other cell lines and the induction of interferon (IFN)-beta and IFN-stimulated genes was at lower levels in CLAC cells. These results suggested that rMV-SLAMblind exhibits oncolytic effect against some canine lung cancer cells and the cellular response after the virus infection may influence its efficacy.

Immuno Histochemical Expression of CD10 OR CA19.9 in Urinary Bladder Transitional Cell Carcinoma

Objectives: To determine the frequency of immunohistochemical expression of CD10 and CA19.9 in patients with papillary urothelial carcinoma of the bladder in accordance with the WHO 2004 grading of the tumor. Methodology: This descriptive cross-sectional study was conducted at the Foundation University Medical College Islamabad, from October 2017 to October 2018. Seventy-five patients from both genders, aged 40 to 80 years, undergoing trans urethral resection of bladder tumors to diagnose papillary urothelial bladder were included in our study. The data were analyzed with SPSS version 17. Immunohistochemical processing was performed and the results were interpreted by the consultant pathologist for the expression of CD10 and CA19.9 on transitional cell carcinoma with respect to the 2004 grading of the tumor. Results: age range in this study was from 40 to 80 years with a mean age of 52.60 ± 7.60 years. Out of these 75 patients, 39 (52.0%) were male and 36 (48.0%) were female, with a male-to-female ratio of 1.1:1. The frequency of positive expression of CD10 and CA19.9 on immunohistochemistry in patients with papillary urothelial carcinoma of the bladder was found in 41 (54.67%) and 39 (52.0%) cases, respectively. It was seen that positive CD10 expression was found in 12 (31.58%) low grade tumors and in 24 (63.16%) high grade tumors. Positive CA19.9 expression was found in 29 (78.38%) low grade tumors and 15 (40.54%) high grade tumors. Conclusion: The study concluded that there was a slightly increased expression of CD10 in transitional cell carcinoma of the urinary bladder compared with CA19.9. However, high-grade urothelial carcinomas showed increased expression of CD10 in contrast to low-grade urothelial carcinomas, which revealed increased positive expression of CA19.9. Â

Cytotoxic effect of Senecio madagascariensis (Asteraceae) extracts on cancer derived cell lines

Species of the genus Senecio have been traditionally employed with medical purposes and it has been demonstrated that some of them have anti-proliferative activity on cancer-derived cell lines. In South America S. madagascariensis is one of the most important representatives of the genus. Almost all species contain pyrrolizidine alkaloids (PA), substances that can lead to hepatic damage. Thus, the aim of this work was to determine the cytotoxic activity of a low PAs extract of S. madagascariensis on a cancer-derived cell line. A chloroform extract from plant material was produced and it was demonstrated to have a PAs concentration lower than 200 μg/g (w/w). Two stock solutions were made with DMSO and acetone as solvents and were diluted in culture medium (DMEM). Cells from urinary bladder transitional cell carcinoma T24 were cultured in 96 well plates (104 cells/well) and incubated for 24 hours with dilutions of the extracts at the following concentrations, 0.5 mg/mL, 0.25 mg/mL, 0.125 mg/mL and 0.06 mg/mL. Cell viability was evaluated by the MTT colorimetric technique. Both solutions of S. madagascariensis extracts (acetone and DMSO) showed cytotoxic activity. In both cases, the degree of cytotoxicity was dependent on the concentration of the solution.

CASC5 is a potential cancer-testis gene in human urinary bladder transitional cell carcinoma.

Urinary Bladder cancer (UBC) is a diversified disease with an array of clinicopathological attributes. Several studies have shown that cancer susceptibility candidate 5 (CASC5) plays important roles in various types of malignancies; however its expression and clinical significance in human UBC remain largely unknown. This research study was intended to explore mRNA/protein expression pattern of CASC5 as a member of the cancer-testis (CT) gene family and assess its clinical utility in diagnostic management of patients with UBC. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) was employed to appraise the detailed expression profile of CASC5 in patients with UBC. The mRNA over expression of CASC5 was detected in testis tissue and relatively high frequency 59.2% (45 of 76) of CASC5 mRNA was detected in UBC tissues. CASC5 mRNA relative mean fold expression was also significantly (p < 0.01) higher in the muscle-invasive tumor tissues compared to non-muscle-invasive tumor tissues (12.26 ± 9.53 vs. 4.64 ± 2.50, p = 0.005). Heterogeneous staining pattern of CASC5 protein was exclusively detected using IHC. The frequency of CASC5 protein over expression was detected in 67.7% (44 of 65) UBC patients and negative in benign prostatic hyperplasia (BPH). Further, CASC5 protein expression was significantly (p < 0.001) associated with cigarette smoking habit in UBC patients. Our study findings testified that CASC5 over expression among patients with UBC as compared to controls and concludes that CASC5 is a potential CT gene in UBC.

Expression of proto-oncogene c-Myc in patients with urinary bladder transitional cell carcinoma

Background:c-Myc is a proto-oncogene located on human chromosome 8. It encodes a transcriptional factor which regulates the expression of approximately 10% to 15% of human genes, playing a crucial role in cell growth, differentiation, cellular metabolism, apoptosis, and cell transformation. The aim of this study is to correlate the expression of c-Myc in patients suffering from urinary bladder transitional cell carcinoma with tumor grade, stage, and lymph node metastases.Materials and methods:Formalin-fixed, paraffin-embedded tissue samples were obtained from 54 consecutive patients who underwent transurethral resection of bladder tumor or radical cystectomy (RC) as treatment for urinary bladder transitional cell carcinoma. Immunohistochemistry was performed using c-Myc monoclonal antibody and c-Myc expression was then analyzed for correlation with tumor stage, grade, and lymph node metastases.Results:From a total of 54 patients, 42 (77.8%) had c-Myc positive staining and 12 (22.2%) were c-Myc negative. In the c-Myc positive group, 28 patients (66.7%) had low grade tumors and 33 (78.6%) presented with non-muscle-invasive disease (p < 0.05). In the c-Myc negative group, 10 patients (83.3%) had high-grade disease and 8 (66.7%) presented with muscle-invasive disease (p < 0.05). Lymph node metastases were evaluated in 17 patients who underwent RC. Of these, 5 had lymph node metastases, 4 of whom had c-Myc negative staining (p < 0.05).Conclusions:In our study, c-Myc negative staining was associated with higher grade and higher stage disease. On the contrary, most c-Myc positive tumors were low grade and non-muscle-invasive disease. In patients who underwent RC, c-Myc negative staining was associated with lymph node metastases.

Frequent expression of a novel cancer testis antigen, protein kinase human monopolar spindle 1 (hMps1/TTK) in human urinary bladder transitional cell carcinoma.

Urothelial bladder cancer (UBC) is a frequently occurring malignancy of the urinary tract. The present study was undertaken to evaluate the mRNA and immunohistochemical (IHC) expression of protein kinase human monopolar spindle 1 (hMps1/TTK) gene in transitional cell carcinoma (TCC) of the bladder and correlate its expression with the clinicopathological characteristics of patients. In the present study, quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate TTK mRNA expression in TCC. IHC analysis of TTK was also evaluated. Independent Student's t, ANOVA and chi-square (χ2) tests were used to analyze the data statistically. The frequency of TTK mRNA over expression was detected in 50% of UBC (38/76) by qRT-PCR. Relative mean fold expression of TTK mRNA was found significantly (p < 0.05) higher in muscle-invasive bladder cancer (MIBC) as compared to non-muscle-invasive bladder cancer (NMIBC) patients (8.96 ± 4.51 vs. 5.64 ± 3.53, p = 0.03). Moreover, IHC reveals heterogenous immunostaining pattern of TTK in TCC tissues. The frequency of TTK protein over expression was detected in 56.9% (37 of 65) UBC patients. No significant IHC expression of TTK was detected among adjacent noncancerous tissues (ANCTs) and benign prostatic hyperplasia (BPH) used as control. Collectively our study observations conclude that TTK is a novel cancer/testis antigen (CTA) as a diagnostic marker for early diagnosis of UBC.

Significance of D2-40 and CXCL5 Expression in Urinary Bladder Transitional Cell Carcinoma: An Immunohistochemical Study

Background: Transitional cell carcinoma remains a challenge in the oncology field, representing an ideal candidate for research on biomarkers that could identify patient’s progression and prognosis. D2-40 and CXCL5 have been implicated in progression of many cancers, but their significance in urinary bladder TCC remains unclear. The aim of this study is to assess their possible significance in urinary bladder transitional cell carcinoma.Methods: Immunohistochemistry was performed to examine the expression of D2-40 and CXCL5 in 50 cases of urinary bladder TCC and 10 cases of normal urothelium taken as a normal control. Statistical analysis methods were used to evaluate the relationship between D2-40 and CXCL5 and various clinicopathological parameters.Results: D2-40 was expressed in the lymphatic endothelial cytoplasm of all cases highlighting the tumor emboli in cancer lymphatic vessels. CXCL5 was found to be expressed in all urinary bladder TCC cases but not in normal control. The two markers significantly correlated with associated necrosis, tumor grade, T, N stage and presence of H&E detected LVI. CXCL5 was also positively correlated with presence of associated necrosis and CIS while D2-40 was insignificantly correlated with both. D2-40 detected intra-lymphatic tumor emboli are associated with lymph node metastasis in a highly significant correlation. Conclusions: The results suggested that CXCL5 might be involved in urinary bladder TCC carcinogenesis. It could be concluded that D2-40 and CXCL5 may have a possible role in urinary bladder TCC progression and prognosis. D2-40 might be considered as more reliable method in predicting tumor spread and lymph-node metastasis.

The Impact of Radiotherapy on the Incidence of Secondary Malignancies: A Pan-Cancer Study in the US SEER Cancer Registries.

The population of cancer patients with second primary malignancies (SPMs) is rapidly growing. The relationship between radiotherapy and SPMs for some types of tumors is unknown or debated. In this study, we identify 24 types of first primary malignancies (FPMs) between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the radiotherapy group were matched to those in the no radiotherapy group with a matching ratio of 1:1. After propensity-score matching (PSM), additional competing risk regression analyses were performed to calculate the efficacy of radiotherapy to SPMs in the PSM-adjusted population. In addition, the Fine and Gray model was utilized in the primary cohorts, and stratified analyses were performed based on surgery. This study includes a total of 2,831,789 eligible patients with tumors diagnosed from 2004 to 2015 in the SEER 18 database, amongst whom 100,194 (3.5%) patients developed SPMs. We observe higher risks of SPMs associated with radiotherapy in several types of tumors in the PSM-adjusted populations (small bowel adenocarcinoma, small cell lung carcinoma, prostate adenocarcinoma, urinary bladder transitional cell carcinoma, invasive ductal breast carcinoma, invasive lobular breast carcinoma, and Hodgkin lymphoma). The results in the PSM-adjusted populations were consistent with outcomes in the multivariable competing risk models. Meanwhile, in subgroup analyses stratified by surgery, some other types of tumor (except for those with positive results in the PSM-adjusted cohorts) with radiotherapy were also associated with a higher prevalence of SPMs in the subgroups of surgical treatment (pancreatic adenocarcinoma, rectal adenocarcinoma, lung adenocarcinoma and follicular thyroid carcinoma in the surgery subgroups). The impact of radiotherapy on the incidence of secondary malignancies is distinct in different types of cancer. These findings merit further investigation and may ultimately impact treatment decision-making for tumor management.

Evaluation of epithelial and mesenchymal cell markers in canine urinary bladder transitional cell carcinoma

Canine transitional cell carcinoma (cTCC) is the most common malignant tumour in the urinary bladder: it is highly invasive and exhibits metastatic characteristics. Inflammation is also strongly related to cTCC. Epithelial tumours often exhibit a mesenchymal cell phenotype during tumour invasion and metastasis owing to epithelial-mesenchymal transition (EMT), which is often induced in chronic inflammation. The aim of this retrospective study was to investigate the expression of epithelial and mesenchymal cell markers in tumour cells and to evaluate its relationship with prognosis of cTCC. In this study, 29 dogs with cTCC who underwent surgical treatment were enrolled. Clinical parameters were reviewed using medical records. Tissue expression of epithelial and mesenchymal markers was evaluated by immunohistochemical analysis. The association between the expression of mesenchymal cell markers and clinical parameters, including prognosis, was statistically examined.In five normal bladder tissues used as controls, no expression of mesenchymal markers was observed, except for one tissue that expressed fibronectin. Conversely, epithelial tumour cells expressed vimentin and fibronectin in 23/29 and 19/28 cTCC tissues, respectively. Regarding clinical parameters, vimentin score in Miniature Dachshunds was significantly higher than those in other dog breeds (P < 0.001). Multivariate survival analyses revealed that age>12 years was related to shorter progression-free survival (P = 0.02). Higher vimentin score, lower fibronectin score, and advanced clinical T stage were significantly correlated with shorter median survival time (P < 0.05). The results of this study indicate that vimentin expression was associated with cTCC progression. Further studies are needed to examine the incidence and relevance of EMT in cTCC.

Urinary Bladder Transitional Cell Carcinoma with Chordoid Features-A Rare Entity

Abstract Casestudy: Invasive urothelial carcinoma is heterogenous entity and show variant morphologic patterns, of which squamous differentiation is the most common. Other variants have been widely recognized and studied. Invasive urothelial carcinoma with chordoid features is a rare entity with only 16 reported cases to date in English literature. It has a significant morphologic overlap with other vesical and non-vesical myxoid neoplasms, including extra-skeletal myxoid chondrosarcoma and chordoma, which necessitate an extensive workup to reach an accurate diagnosis. To the best of our knowledge we report the 17th case of urothelial carcinoma with chordoid features in a 76-year-old male who underwent a cystoprostatectomy and bilateral pelvic lymph node dissection with confirmed diagnosis of high-grade invasive urothelial carcinoma on biopsy. Grossly, bladder showed a 4.2 x 3.4 x 0.6 cm firm white tumor entirely replacing the anterior wall, extending into perivesicular fat, and invading the prostate gland and seminal vesicles. Microscopically, tumor showed urothelial carcinoma in-situ transitioning into high-grade invasive carcinoma with chordoid features. The tumor characterized by round to elongated epithelial cells and eosinophilic cytoplasm arranged in a single file/complex cord-like architecture, in a prominent myxoid stromal background. No conventional high-grade spindle cell morphology was identified. Pelvic lymph nodes were positive for metastatic disease. Tumor cells were positive for GATA3, Pan-cytokeratin, 34BetaE12, and p63, while negative for AMCAR, supporting the urothelial origin of this tumor and confirming the diagnosis. Invasive urothelial carcinoma with chordoid features is a rare entity, generally present at high stage disease, that can be mistaken for other prominent myxoid stromal neoplasms and requires careful assessment. Although, it can demonstrate similar demographic, clinical and immunohistochemical staining pattern as of conventional urothelial carcinoma, special attention should be given to exclude sarcomatoid features which is an aggressive variant of urothelial carcinoma.

Antitumor activity of an oncolytic measles virus against canine urinary bladder transitional cell carcinoma cells

The prognosis of canine transitional cell carcinoma (TCC) of urinary bladder is generally poor because it is difficult to diagnose at early stages and conventional therapies, such as surgical resection and/or chemotherapy, are often not curative treatments. Based on our previous report that recombinant measles virus (rMV-SLAMblind) therapy could be a new treatment for canine mammary tumor, the applicability of rMV-SLAMblind in canine urinary bladder TCC was examined in this study. A canine TCC cell line was established from a TCC patient dog by transplanting a piece of the tumor mass into an immunodeficient mouse and then isolating the primary TCC cells from the grown tumor mass. The primary cultured cells, named TCC-NU1, express nectin-4, a receptor for rMV-SLAMblind infection. The rMV-SLAMblind infected TCC-NU1 cells, and dose-dependently showed cell cytotoxicity. Moreover, intratumoral administration of rMV-SLAMblind in a xenograft model bearing TCC-NU1 cells significantly suppressed the tumor growth reducing the endpoint mass of tumors in treated mice compared to control mice. These results suggest that virotherapy with rMV-SLAMblind be a new candidate therapy for canine TCC.

Immunohistochemistry Study Urothelial Carcinoma using Tumor Markers (EGFR, EMA and CD117)

The aim of the present is to determine the immunohistochemical expression of EGFR, EMA and CD117 in case of urinary bladder transitional cell carcinoma and their relation with staging of tumor and its impact on further prognosis. EGFR immunohistochemical study showing (61.5 %) positive in case of urinary bladder carcinoma with significant difference between staging of tumor (p value 0.019) with signification expression between low grade and high grade tumor with P value 0.002 (6.2%) positivity in high grade versus (15.4 %) positivity in low grade). EMA showing strong positivity in urothelial carcinoma 96.2% without significant difference between staging and grading of tumor with p valve of (0.57) and (0.227) respectively CD117 immunohistochemical study showing total positive cases of urinary bladder carcinoma of 69.2% with significant difference in comparison with staging and grading of tumor with (P-value=0.00) for each respectively. Our result demonstrate that EGFR and CD 117 immunohistochemical staining showing strong positivity in majority of urothelial carcinoma cases with significant relation to both pathological grading and staging of tumor. Application of both markers may play a role to give idea about behavior of tumor and possibility of further recurrence with and even direct therapy application EMA showing strong positive expression which give idea about tumor origin from epithelial lining. It had no benefit in assessment of tumor grading and staging

Effects of Epigallocatechin Gallate (EGCG) on Urinary Bladder Urothelial Carcinoma-Next-Generation Sequencing and Bioinformatics Approaches.

Background and objectives: Bladder urothelial carcinoma is the most common type of genitourinary cancer. Patients with bladder cancer may have limited treatment efficacy related to drug toxicity, resistance or adverse effects, and novel therapeutic strategies to enhance treatment efficacy or increase sensitivity to drugs are of high clinical importance. Epigallocatechin gallate (EGCG) is a polyphenolic compound found in green tea leaves, and a potential anti-cancer agent in various cancer types through modulating and regulating multiple signaling pathways. The current study aimed to explore the role and novel therapeutic targets of EGCG on bladder urothelial carcinoma. Materials and Methods: The BFTC-905 cells, human urinary bladder transitional cell carcinoma (TCC) cell line, were treated with EGCG or water for 24 hours, and the expression profiles of mRNAs and microRNAs were analyzed using next generation sequencing (NGS). The enriched biological functions were determined using different bioinformatics databases. Results: A total of 108 differentially expressed genes in EGCG-treated bladder TCC cells were identified, which were mainly involved in nicotinamide adenine dinucleotide (NAD) biogenesis, inflammatory response and oxidation-reduction metabolism. Moreover, several microRNA-mRNA interactions that potentially participated in the response of bladder TCC to EGCG treatment, including miR-185-3p- ARRB1 (arrestin beta 1), miR-3116- MGAT5B (alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B), miR-31-5p-TNS1 (tensin 1), miR-642a-5p-TNS1, miR-1226-3p- DLG2 (discs large homolog 2), miR-484-DLG2, and miR-22-3p- PPM1K (protein phosphatase 1K). Conclusions: The current findings provide insights into novel therapeutic targets and underlying mechanisms of action of EGCG treatment in bladder cancer.

Optical sensory arrays for the detection of urinary bladder cancer-related volatile organic compounds.

Non‐invasive detection of urinary bladder cancer remains a significant challenge. Urinary volatile organic compounds (VOCs) are a promising alternative to cell‐based biomarkers. Herein, we demonstrate a novel diagnosis system based on an optic fluorescence sensor array for detecting urinary bladder cancer VOCs biomarkers. This study describes a fluorescence‐based VOCs sensor array detecting system in detail. The choice of VOCs for the initial part was based on an extensive systematic search of the literature and then followed up using urinary samples from patients with urinary bladder transitional cell carcinoma. Canonical discriminant analysis and partial least squares discriminant analysis (PLS‐DA) were employed and correctly detected 31/48 urinary bladder cancer VOC biomarkers and achieved an overall 77.75% sensitivity and 93.25% specificity by PLS‐DA modelling. All five urine samples from bladder cancer patients, and five healthy controls were successfully identified with the same sensor arrays. Overall, the experiments in this study describe a real‐time platform for non‐invasive bladder cancer diagnosis using fluorescence‐based gas‐sensor arrays. Pure VOCs and urine samples from the patients proved such a system to be promising; however, further research is required using a larger population sample.

Unusual case of metastasis of urinary bladder Transitional cell carcinoma to the gingival

Unusual case of metastasis of urinary bladder Transitional cell carcinoma to the gingival

Ultrasound characteristics of feline urinary bladder transitional cell carcinoma are similar to canine urinary bladder transitional cell carcinoma

Feline transitional cell carcinoma (TCC) is a rare neoplasia of cats with an estimated prevalence of 0.18%. Cats with TCC share clinical signs with common pathologies like feline idiopathic cystitis or urinary tract infections. Nonspecific clinical signs include hematuria, pollakiuria, or stranguria. The literature lacks a feline-specific ultrasound description of TCC. The aim of this multicenter retrospective descriptive study was to report ultrasound findings of a collection of feline TCC and then assess if feline TCC and canine TCC have similar ultrasound appearances. It was hypothesized that the ultrasound characteristics would be similar between feline and canine TCC. Ultrasound studies were assessed for tumor shape, number of isolated mural masses, location within the bladder, presence of Doppler signal, echogenicity of urine, mineralization within the mass, extension of the mass into the proximal urethra or ureters, urethral/ureteral obstruction, pyelectasia, and sublumbar lymphadenopathy. Feline studies were compared to 20 cases of confirmed canine TCC. A total of 20 cats with histologically or cytologically confirmed diagnosis of TCC were included. Feline and canine TCC had similarities when viewed using ultrasound. Statistically significant differences were identified for location of the bladder mass (cats were more likely to be mid-body vs trigonal in dogs, P=.011) and urethral extension of the tumor was less likely in cats than dogs (P=.0436). Based on this sample of 20 cats, feline TCC was most commonly a singular, broad-based mass within the mid-body or apex of the urinary bladder.

46 - Urinary bladder transitional cell carcinoma in patients of age below 40

46 - Urinary bladder transitional cell carcinoma in patients of age below 40

Fluid Shear Stress Induces Cell Cycle Arrest in Human Urinary Bladder Transitional Cell Carcinoma Through Bone Morphogenetic Protein Receptor-Smad1/5 Pathway.

Mechanical force generated from the interstitial fluid flow inside and surrounding tissue has been known to play a significant role in cancer pathophysiology. In this study, we aimed to investigate the role of laminar shear stress (LSS) in modulating the cell cycle of human bladder transitional carcinoma (BFTC-905) cells which are frequently stimulated by not only the interstitial fluid flow, but also the urine flow transported from kidney to bladder in the urinary tract. The BFTC-905 cells were subjected to 0-12 dynes cm-2 LSS for 1, 4, 8, or 12h, respectively, followed by cellular and molecular assays for investigations of cell cycle regulation protein expressions, cell growth rates, and the potential mechanism. The results showed that the LSS with ≥ 8 dynes cm-2 for ≥ 8h significantly increased protein expressions of cyclin B1, Wee1, p21, and p-CDK1(Tyr15) (p < 0.05 for each), but conversely decreased protein expressions of cyclin A2, D1, E1, and CDK-1, -2, -4, and -6 (p < 0.05 for each) in the BFTC-905 cells, indicating that a G2/M cell cycle arrest was obtained after shearing stimulation. Furthermore, our data demonstrated that the LSS-induced G2/M arrest and the corresponding changes in cell cycle regulatory protein expressions were modulated by bone morphogenetic protein (BMP) receptor-Smad1/5 signaling pathway. Our findings provided evidences for the effect of mechanical microenvironment on urothelial cancer pathobiology and generated insights into mechanism of LSS-regulated bladder tumor cell cycle.

Effect of Pretreatment of Morin on the Cisplatin-Induced Toxicity on LLC-PK1 and T24 Cells

Cisplatin is a chemotherapeutic drug broadly used in the treatment of solid tumors. However, patients under this chemotherapy develop severe adverse effects, being nephrotoxicity the most frequent. Cisplatin-induced nephrotoxicity has been associated with oxidative stress, inflammation and apoptosis. Morin, a rather abundant flavonoid, presents antioxidant properties and, at the same time, decreases viability in some tumor cells. Taking into account these facts, it has been hypothesized that morin could attenuate cisplatin-induced kidney injury without interfering with antineoplastic activity of cisplatin. The aim of this study was to evaluate the potential cytoprotective effect of morin against cisplatin-induced damage in the Lilly Laboratories cell-porcine kidney 1 (LLC-PK1) cell line. In addition, the effect of pretreatment with morin on the toxicity of cisplatin on human urinary bladder transitional cell carcinoma T24 cell line was investigated. It was found that 200 μM morin attenuates cisplatin-induced damage on LLC-PK1 cells in a heme oxygenase-1 (HO-1) dependent-way. Moreover, it was found that 200 μM morin alone, decreases T24 cell viability in the same proportion as cisplatin. However, when T24 cells were pretreated with morin, the cell viability did not change compared to the cells treated only with cisplatin.

Quantitative evaluation of canine urinary bladder transitional cell carcinoma using contrast-enhanced ultrasonography

BackgroundIn veterinary medicine, contrast-enhanced ultrasonography allowed the accurate quantification of liver, splenic and kidney vascularization in healthy dogs and the differentiation between malignant and benign hepatic, renal, and splenic nodules in dogs and cats based on perfusion patterns. The utility of contrast-enhanced ultrasonography in other applications is still under study.The aim of this study was to develop diagnostic criteria by contrast-enhanced ultrasonography in 8 client-owned adult dogs affected by urinary bladder transitional cell carcinoma with definitive diagnosis made by cytopathologic evaluation after suction biopsy. The contrast enhancement pattern and the quantification of blood flow parameters of this tumor were reported.ResultsExaminations with B-mode, Doppler ultrasonography and contrast-enhanced ultrasonography were performed in all not sedated dogs. Assessments of bladder masses and bladder wall infiltration were performed. Each dog received 2 bolus injections of sulfur hexafluoride during the contrast-enhanced ultrasonography. Quantitative analysis of the contrast-enhanced ultrasonography images were performed. For each dog, one region of interest was manually drawn around the entire tumor. Software analysis of contrast-enhanced time-intensity curves was used to identify peak enhancement, time to peak enhancement, regional blood volume, regional blood flow, and mean transit time.Contrast-enhanced ultrasonography showed an avid enhancement of the tumour tissue, with a heterogeneous or homogeneous pattern. The exam also showed the loss of planes between the lesion and the muscular layer. The presence of vascularized tissue through the bladder wall confirms the infiltrative feature of the tumour. Post-processing quantitative analysis showed a time-intensity curve with a rapid wash-in, a low level of signal intensity and a slow wash-out.ConclusionsContrast-enhanced ultrasonography provided useful clinical information and defined a vascular enhancement patterns and calculated parameters associated with TCC. It may be a useful, noninvasive and reproducible tool for detecting these tumors in dogs.