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bladder cancer - Top 30 Publications

Parallel PI3K, AKT and mTOR inhibition is required to control feedback loops that limit tumor therapy.

Targeting the PI3K pathway has achieved limited success in cancer therapy. One reason for the disappointing activity of drugs that interfere with molecules that are important player in this pathway is the induction of multiple feedback loops that have been only partially understood. To understand these limitations and develop improved treatment strategies, we comprehensively characterized molecular mechanisms of PI3K pathway signaling in bladder cancer cell lines upon using small molecule inhibitors and RNAi technologies against all key molecules and protein complexes within the pathway and analyzed functional and molecular consequences. When targeting either mTORC1, mTOR, AKT or PI3K, only S6K1 phosphorylation was affected in most cell lines examined. Dephosphorylation of 4E-BP1 required combined inhibition of PI3K and mTORC1, independent from AKT, and resulted in a robust reduction in cell viability. Long-term inhibition of PI3K however resulted in a PDK1-dependent, PIP3 and mTORC2 independent rephosphorylation of AKT. AKT rephosphorylation could also be induced by mTOR or PDK1 inhibition. Combining PI3K/mTOR inhibitors with AKT or PDK1 inhibitors suppressed this rephosphorylation, induced apoptosis, decreased colony formation, cell viability and growth of tumor xenografts. Our findings reveal novel molecular mechanisms that explain the requirement for simultaneous targeting of PI3K, AKT and mTORC1 to achieve effective tumor growth inhibition.

Is there different risk of cancer among end-stage renal disease patients undergoing hemodialysis and peritoneal dialysis?

Cancer is a global issue in recent decade. Despite this alarming increase in the incidence of cancer, to date, whether the risk of developing cancer differs among peritoneal dialysis (PD) and hemodialysis (HD) patients is still uncertain. In this retrospective cohort study, data were obtained from the National Health Insurance Research Database of Taiwan, which provides coverage to almost 99% of the nation's population. After matching, a total of 4491 (or 3369) incident PD patients and 8982 (or 6738) incident HD patients between 2000 and 2009 were enrolled from the database. In addition, 22,455 (or 16,845) nondialysis patients were selected as a control group. The patients were monitored for the occurrence of cancer until 2010, and their data were analyzed using several different models. In general, the results showed that the risks of hepatocellular, kidney, bladder, extra kidney/bladder urinary tract, and thyroid cancers were higher in dialysis patients. We also compared the risk of cancer between two dialysis groups by using the HD patients as the reference group. The result showed that there is no significant different for each cancer risk between two dialysis groups. In conclusion, dialysis patients had a higher risk of certain types of cancer than those in the nonuremia group. However, there was no significant difference in the cancer risk between the two dialysis groups when compared directly.

Impact of body mass index on the oncological outcomes of patients with upper and lower urinary tract cancers treated with radical surgery: A multi-institutional retrospective study.

To evaluate the impact of body mass index (BMI) on the oncological outcomes of urothelial carcinoma (UC) patients.

Long noncoding RNA BLACAT2 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis.

The prognosis for bladder cancer patients with lymph node (LN) metastasis is dismal and only minimally improved by current treatment modalities. Elucidation of the molecular mechanisms that underlie LN metastasis may provide clinical therapeutic strategies for LN-metastatic bladder cancer. Here, we report that a long noncoding RNA LINC00958, which we have termed bladder cancer-associated transcript 2 (BLACAT2), was markedly upregulated in LN-metastatic bladder cancer and correlated with LN metastasis. Overexpression of BLACAT2 promoted bladder cancer-associated lymphangiogenesis and lymphatic metastasis in both cultured bladder cancer cell lines and mouse models. Furthermore, we demonstrate that BLACAT2 epigenetically upregulated VEGF-C expression by directly associating with WDR5, a core subunit of human H3K4 methyltransferase complexes. Importantly, administration of an anti-VEGF-C antibody inhibited LN metastasis in BLACAT2-overexpressing bladder cancer. Taken together, these findings uncover a molecular mechanism in the lymphatic metastasis of bladder cancer and indicate that BLACAT2 may represent a target for clinical intervention in LN-metastatic bladder cancer.

Halting Schistosoma haematobium - associated bladder cancer.

At present schistosomiasis is endemic in 78 countries affecting more than 260 million people. Schistosomiasis haematobia alone affects more than 112 millions.

Next-generation sequencing in non-muscle-invasive bladder cancer-a step towards personalized medicine for a superficial bladder tumor.

Online tools for patient counseling in bladder and kidney cancer-ready for prime time?

Gauging prognosis is a key element when facing treatment decisions in cancer care. Several prognostic tools, such as risk tables and nomograms are at hand to aid this process. In the context of patient-centered care, prognostic tools are of great interest to caregivers and -providers alike, as they can convey sizeable amounts of information and provide tailored, accurate estimates of prognosis. Given the rising number of prognostic tools in cancer care over the last two decades, and similarly, ever increasing presence of the Internet, we aimed to assess how this would translate into the availability of online tools for patient counseling. We used a modified systematic review to evaluate the web-based availability, format, and content of prognostic tools for bladder and kidney cancer care. Our search identified a total of twenty-three tools, offered by eight providers, which assessed a total of six (bladder cancer) and five (kidney cancer) different outcomes. Despite the restricted availability of online tools, we observed that the majority showed limited user-friendliness (including, for example, a statement/explanation of intended use, visualization of data, availability as application software for handheld devices). Only one tool included modifiable risk factors such as smoking behavior and body weight. Lastly, none of the tools incorporated genomic or molecular markers or treatment associated quality of life. Taken together, online tools for patient counseling in bladder and kidney cancer care are only beginning to align with the growing need in clinical reality. Further and future avenues include incorporation of health-related quality of life as well as genomic and biomarkers into prediction tools.

Perspective on cytoreduction and metastasis-directed therapy in node positive and metastatic urothelial carcinoma of the bladder.

The outcome of node positive or metastatic urothelial carcinoma of the bladder (mUCB) is poor and palliative chemotherapy has long been considered the only treatment option for this patient group. Cytoreduction and metastasis-directed therapy, either by surgery or radiotherapy, has been successfully applied in other metastatic solid tumors in order to increase survival. In this article, we explore the literature supporting cytoreduction and metastasis-directed therapy in node positive and mUCB and try to define a patient cohort that could benefit from these treatments. From these data, it is clear that a selected group of patients survive a long time or could even be cured, however the data are scarce and the level of evidence is low. The criteria of a randomized clinical trial, to deliver the necessary evidence, are proposed.

Current markers and their value in the era of immuno-oncology.

Immunotherapy in urothelial cancer is a quickly evolving field as new agents are being investigated in multiple clinical trials and various clinical settings. The purpose of this review is to provide an insight into the mechanism of these treatments, potential targets to evaluate treatment response and to give an update on the current status of clinical trials. Urothelial cancer is a polyclonal disease with a substantial tumor heterogeneity and a high mutational load which may be beneficial as this may trigger a stronger T-cell mediated immune response. PD-1 expression has been shown to correlate with stage, grade, progression and poorer survival but it appears challenging to be utilized as a predictor for treatment response in urothelial cancer. Another important concept is immune cell (IC) infiltration, which is a reflection of the activated immune response within the target tissue. Marker genes may represent signaling pathways involved in T-cell recognition and lysis of T-cells. The complexity of the tumor and host interaction requires multiple concepts to be integrated into a future model to assess treatment response. We have evaluated multiple biomarker approaches currently investigated in clinical trials in urothelial cancer.

The current status and clinical value of circulating tumor cells and circulating cell-free tumor DNA in bladder cancer.

Urothelial carcinoma of the bladder (UCB) is a complex disease, which is associated with highly aggressive tumor biologic behavior, especially in patients with muscle-invasive and advanced tumors. Despite multimodal therapy options including surgery, radiotherapy and chemotherapy, UCB patients frequently suffer from poor clinical outcome. Indeed, the potential of diverse opportunities for modern targeted therapies is not sufficiently elucidated in UCB yet. To improve the suboptimal treatment situation in UCB, biomarkers are urgently needed that help detecting minimal residual disease (MRD), predicting therapy response and subsequently prognosis as well as enabling patient stratification for further therapies and therapy monitoring, respectively. To date, decision making regarding treatment planning is mainly based on histopathologic evaluation of biopsies predominantly derived from the primary tumors and on clinical staging. However, both methods are imperfect for sufficient outcome prediction. During disease progression, individual disseminated tumor cells and consecutively metastases can acquire characteristics that do not match those of the corresponding primary tumors, and often are only hardly assessable for further evaluation. Therefore, during recent years, strong efforts were directed to establish non-invasive biomarkers from liquid biopsies. Urine cytology and serum tumor markers have been established for diagnostic purposes, but are still insufficient as universal biomarkers for decision-making and treatment of UCB patients. To date, the clinical relevance of various newly established blood-based biomarkers comprising circulating tumor cells (CTCs), circulating cell-free nucleic acids or tumor-educated platelets is being tested in cancer patients. In this review we summarize the current state and clinical application of CTCs and circulating cell-free tumor DNA originating from blood as biomarkers in patients with different UCB stages.

Genetic determinants for chemo- and radiotherapy resistance in bladder cancer.

Bladder cancer (BCa) is burdened by high rates of chemo- and radio-resistance. We reviewed and summarized the current evidence regarding the genetic determinants of resistance in patients treated with chemotherapy and/or radiotherapy (RT) for BCa. Genetic heterogeneity may preexist to treatment arising with tumorigenesis or increasing progressively during the treatment. Several biological pathways seem to be involved in the cellular response to treatment. These pathways comprehend mechanisms leading to modify the intracellular concentration of the drug, mechanisms leading to increase the repair of DNA damage caused by the treatment, mechanisms leading to increase cell survival, despite DNA damage, acting on the signaling pathways affecting apoptosis, mechanisms promoting autophagy. In the present review, we focused on the genetic determinants of resistance affecting the aforementioned mechanisms.

Do we have biomarkers to predict response to neoadjuvant and adjuvant chemotherapy and immunotherapy in bladder cancer?

Radical cystectomy (RC) is the standard of care treatment of localized muscle-invasive bladder cancer (BC). However, about 50% of patients develop metastases within 2 years after cystectomy. Neoadjuvant cisplatin-based chemotherapy before cystectomy improves the overall survival (OS) in patients with muscle-invasive BC. Pathological response to neoadjuvant treatment is a strong predictor of better disease-specific survival. Nevertheless, some patients do not benefit from chemotherapy. The identification of reliable biomarkers enabling clinicians to identify patients who might benefit from chemotherapy is a very important clinical task. An identification tool could lead to individualized therapy, optimizing response rates. In addition, unnecessary treatment with chemotherapy which potentially leads to a loss of quality of life and which might also might cause a delay of cystectomy in a neoadjuvant setting could be avoided. The present review aims to summarize and discuss the current literature on biomarkers for the prediction of response to systemic therapy in muscle-invasive BC. Tremendous efforts in genetic and molecular characterization have led to the identification of predictive candidate biomarkers in urothelial carcinoma (UC), although prospective validation is pending. Ongoing clinical trials examining the benefit of individual therapies in UC of the bladder (UCB) by molecular patient selection hold promise to shed light on this question.

Different stages in drug development for muscle-invasive bladder cancer.

Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease. Despite optimal therapy, half of the patients will succumb to disease. This prognosis could not be improved over the last three decades. Therefore, MIBC is left behind from other cancers such as prostate, where novel treatment options were discovered and improve patient outcomes. While being aware of the recent emerging evidence of checkpoint inhibition in MIBC, we aim to describe different stages of drug development in MIBC by using three specific targets. On the example of Her2 targeting, we aimed to indicate, that either a target is ineffective in MIBC or that the patient selection is insufficient. The first clinical trials using a pan fibroblast growth factor receptor (panFGFR) inhibitor to target the FGFR pathway showed promising results. Data of further trials are to be awaited before implementing these drugs into daily clinical practice. A large variety of novel agents are investigated in vitro and in vivo. On the example of a malaria protein, we aimed to discuss a treatment paradigm that is not dependent on pathway signaling and the genomic landscape of MIBC. The ultimate question still remains to be answered: How do we select the optimal treatment for the right patient?

Peri-operative chemotherapy for muscle-invasive bladder cancer: status-quo in 2017.

The role of perioperative chemotherapy associated with radical cystectomy (RC) for muscle-invasive bladder cancer has been analyzed in several landmark randomized controlled trials (RCTs) over the past decades. With regard to neoadjuvant chemotherapy (NAC), a meta-analysis of level 1 evidence and long-term results from the largest RCTs support its use, which is currently advocated as the standard of care by most of the clinical guidelines worldwide. However, with regard to the delivery of adjuvant chemotherapy (AC), evidence is more contentious. Specifically, several meta-analyses demonstrated a survival benefit associated with the use of cisplatin-based regimen but investigators identified multiple methodological limitations in most of included RCTs. Nonetheless, AC is currently considered for fit patients with adverse pathological features at RC. It is noteworthy that the delivery of such cytotoxic treatment after surgery may maintain significant anti-tumor activity even in those patients who previously received NAC. Finally, given its greater response rate, the methotrexate, vinblastine, adriamycin plus cisplatin combination remains preferentially considered in the neoadjuvant setting, while the gemcitabine plus cisplatin combination is more commonly delivered in the adjuvant setting because of its better toxicity profile. However, no prospective evidence comparing efficacy of both regimens for NAC or AC is currently available.

Opportunities of next-generation sequencing in non-muscle invasive bladder cancer outcome prediction.

Bladder cancer (BC) is a common disease in both sexes and majority of cases present as non-muscle invasive BC (NMIBC). The percentage of NMIBC progressing to muscle invasive BC (MIBC) varies between 25% and 75% and currently there are no reliable biomarkers that may predict the outcome of high-risk (HR) NMIBC. Whilst The Cancer Genome Atlas (TCGA) project has identified genetic alteration in MIBC using next-generation sequencing (NGS), genetic data in HR-NMIBC outcome prediction using this new technology are limited. We reviewed data on NGS performed on DNA and RNA extracted from tissue, plasma and urinary samples obtained from patients with NMIBC. Analysis on different specimens revealed genetic alterations and microRNA alterations in common oncogenic pathways such as gene expression (TERT) and cell proliferation (PTEN, cyclin D). Validation of a 12-gene (CDC25B, KPNA2, BIRC5, COL18A1, MSN, UBE2C, COL4A1, FABP4, MBNL2, SKAP2, COL4A3BP, NEK1) progression score has shown significant association with progression. ARID1A mutations are associated with an increased risk of recurrence after Bacillus Calmette-Guerin (BCG) together with a high DNA damage repair (DDR) gene alterations in HR-NMIBC. Patients with progressive disease seem to have significantly higher levels of both plasma and urinary tumour DNA compared with patients with recurrence. Although experimental data appear promising, well-designed systematic studies are urgently needed to translate applicability to clinical practice.

The contemporary role and impact of urine-based biomarkers in bladder cancer.

Despite advances in the surgical and medical treatment of bladder cancer, there have only been minor improvements in mortality and morbidity rates over the past decades. Urine-based markers help to improve diagnosing bladder cancer with the aim of complementing or probably in future replacing cystoscopy. Biomarkers may allow individualized risk stratification and support decision-making regarding therapy and follow-up. This review summarizes the existing urine-based biomarkers in bladder cancer. We conducted a comprehensive review of the literature. We conducted a PubMed/Medline based research on English language articles and selected original articles and review articles that provided both description and assessment of urinary markers at time of screening, initial diagnosis, monitoring and prognostic evaluation of urothelial bladder cancer. Our research covered studies published between 2000 and 2017. The aim of this study was to give clinicians keys to understand the existing or promising urinary markers that may become alternatives to cytology/cystoscopy pair in the near future. Many urinary markers are now available, often with superior sensitivity to cytology. Their uses have been evaluated in numerous clinical situations in addition to the time of initial diagnosis and surveillance such as cases of isolated macroscopic hematuria or atypical cytology discordant with the rest of the explorations. However, their superiority over the cytology/cystoscopy association is not demonstrated. These new markers are lacking for the most part of standardization and simplicity making their use in common practice difficult. the types and forms of these new markers are very heterogeneous among themselves and between the studies that evaluate them. Well-designed protocols and prospective, controlled trials are needed to provide the basis to determine whether integration of urine- and blood-based biomarkers into clinical decision-making will be of value for bladder cancer detection and screening in the future.

The landscape of genetics and biomarkers in bladder cancer.

Impact of the Ki-67 labeling index and p53 expression status on disease-free survival in pT1 urothelial carcinoma of the bladder.

The identification of protein biomarkers to guide treatment decisions regarding adjuvant therapies for high-risk non-muscle-invasive bladder cancer (NMIBC) has been of increasing interest. Evidence of the impact of tumor suppressor gene product p53 and cell proliferation marker Ki-67 on oncologic outcomes in bladder cancer patients at highest risk of recurrence and progression is partially contradictory. We sought to mirror contemporary expression patterns of p53 and Ki-67 in a select cohort of patients with pT1 bladder cancer.

Erratum to: Hafeez S, McDonald F, Lalondrelle S, et al. Clinical outcomes of image guided adaptive hypofractionated weekly radiation therapy for bladder cancer in patients unsuitable for radical treatment. Int J Radiat Oncol Biol Phys 2017;98:115-122.

High Resolution Melting Analysis for Rapid Detection of PIK3CA Gene Mutations in Bladder Cancer: A Mutated Target for Cancer Therapy.

PIK3CA gene mutations have clinical importance and their presence is associated with therapy response. They are also considered as a molecule for targeted therapy. As regards to their importance, genetic variation within a population as well as among different populations, this study was conducted to detect common mutations of exons 9 and 20 and other probable mutations in PIK3CA gene as well as their frequencies in Iranian bladder cancer patients.

Safety and Efficacy of Prostatic Artery Chemoembolization for Prostate Cancer-Initial Experience.

To evaluate outcome of prostatic artery chemoembolization for patients with prostate cancer (PCa).

Hepatic Mass in a Patient With Bladder Cancer History.

High expression of TMEM40 is associated with the malignant behavior and tumorigenesis in bladder cancer.

Bladder cancer (BCa) is one of the most common cancers in the urinary system among the world. Previous studies suggested that TMEM40 expression level was significantly associated with clinicopathological parameters including histological grade, clinical stage and pT status of bladder cancer. However, the molecular mechanism of TMEM40 in BCa remains poorly understood.

Effects of microRNA-135a on the epithelial-mesenchymal transition, migration and invasion of bladder cancer cells by targeting GSK3β through the Wnt/β-catenin signaling pathway.

This study investigated the effects of microRNA-135a (miR-135a) targeting of glycogen synthase kinase 3β (GSK3β) on the epithelial-mesenchymal transition (EMT), migration and invasion of bladder cancer (BC) cells by mediating the Wnt/β-catenin signaling pathway. BC and adjacent normal tissues were collected from 165 BC patients. Western blotting and quantitative real-time PCR were used to detect the expression of GSK3β, β-catenin, cyclinD1, E-cadherin, vimentin and miR-135a in BC tissues and cells. Cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, small interfering RNA (siRNA)-GSK3β or miR-135a inhibitors+siRNA-GSK3β groups. miR-135a, β-catenin, cyclinD1 and vimentin expression increased, while GSK3β and E-cadherin expression decreased in BC tissues compared with adjacent normal tissues. Compared with the blank and NC groups, the expression of miR-135a, β-catenin, cyclinD1 and vimentin was higher, and cell proliferation, migration, invasion and tumor growth were increased in the miR-135a mimics and siRNA-GSK3β groups. These groups showed an opposite trend in GSK3β and E-cadherin expression and cell apoptosis. The miR-135a inhibitors group was inversely correlated with the blank and NC groups. It was concluded that miR-135a accelerates the EMT, invasion and migration of BC cells by activating the Wnt/β-catenin signaling pathway through the downregulation of GSK3β expression.

Differential expression of cytokeratin 14 and 18 in bladder cancer tumorigenesis.

It has been previously suggested that cytokeratins (CKs) are important diagnostic and prognostic biomarkers for urothelial lesions. Hence it is imperative to understand the expression pattern of cytokeratins during formation of papillary bladder cancer, which was the objective of the current study. Expression pattern of CK14 and CK18 were examined using immunohistochemical staining in a mice model of papillary bladder cancer. Twenty female mice were divided into two groups-group 1 (NT) and group 2, which received N-butyl- N-(4-hydroxybutyl) nitrosamine (BBN) for 20 weeks plus one week without treatment. Following histological classification of bladder lesions, CK14 and CK18 immunostaining was assessed according to its distribution and intensity. In NT animals, both basal cells and umbrella cells showed sporadic positive staining for CK14 and CK18, respectively. In BBN group, hyperplastic lesions showed significantly more CK14 and significantly less CK18 staining ( P < 0.05 in each case). Invasive carcinomas showed increased CK14 immunostaining in all epithelial layers. Cumulatively, our data indicate that altered CK14 (high) and CK18 (low) expression is perhaps an early event in bladder cancer tumorigenesis in females at least and is characteristic of both urothelial superficial pre-neoplastic and neoplastic lesions. Impact statement Studies have shown that expression of cytokeratins (CKs) or their altered distribution affects the bladder cancer pathogenesis and disease outcome, while the underlying mechanisms are not clear. The present study aims to explore the expression pattern of CK14 and CK18 during formation of papillary bladder cancer. The results showed that hyperplastic lesions showed significantly more CK14 and significantly less CK18 staining and invasive carcinomas showed increased CK14 immunostaining in all epithelial layers in N-butyl- N-(4-hydroxybutyl)nitrosamine (BBN)-induced mouse model. The results indicate that altered CK14 (high) and CK18 (low) expression is perhaps an early event in bladder cancer tumorigenesis and is characteristic of both urothelial superficial pre-neoplastic and neoplastic lesions, which may provide the early diagnosis index.

Patient's specific integration of OAR doses (D2 cc) from EBRT and 3D image-guided brachytherapy for cervical cancer.

The objective of this study was to assess the recommended DVH parameter (e.g., D2 cc) addition method used for combining EBRT and HDR plans, against a reference dataset generated from an EQD2-based DVH addition method. A revised DVH parameter addition method using EBRT DVH parameters derived from each patient's plan was proposed and also compared with the reference dataset. Thirty-one biopsy-proven cervical cancer patients who received EBRT and HDR brachytherapy were retrospectively analyzed. A parametrial and/or paraaortic EBRT boost were clinically performed on 13 patients. Ten IMRT and 21 3DCRT plans were determined. Two different HDR techniques for each HDR plan were analyzed. Overall D2 cc and D0.1 cc OAR doses in EQD2 were statistically analyzed for three different DVH parameter addition methods: a currently recommended method, a proposed revised method, and a reference DVH addition method. The overall D2 ccEQD2 values for all rectum, bladder, and sigmoid for a conformal, volume optimization HDR plan generated using the current DVH parameter addition method were significantly underestimated on average -5 to -8% when compared to the values obtained from the reference DVH addition technique (P < 0.01). The revised DVH parameter addition method did not present statistical differences with the reference technique (P > 0.099). When PM boosts were considered, there was an even greater average underestimation of -8~-10% for overall OAR doses of conformal HDR plans when using the current DVH parameter addition technique as compared to the revised DVH parameter addition. No statistically significant differences were found between the 3DCRT and IMRT techniques (P > 0.3148). It is recommended that the overall D2 cc EBRT doses are obtained from each patient's EBRT plan.

GP73 promotes invasion and metastasis of bladder cancer by regulating the epithelial-mesenchymal transition through the TGF-β1/Smad2 signalling pathway.

This study investigated the effects of Golgi membrane protein 73 (GP73) on the epithelial-mesenchymal transition (EMT) and on bladder cancer cell invasion and metastasis through the TGF-β1/Smad2 signalling pathway. Paired bladder cancer and adjacent tissue samples (102) and normal bladder tissue samples (106) were obtained. Bladder cancer cell lines (T24, 5637, RT4, 253J and J82) were selected and assigned to blank, negative control (NC), TGF-β, thrombospondin-1 (TSP-1), TGF-β1+ TSP-1, GP73-siRNA-1, GP73-siRNA-2, GP73-siRNA-1+ TSP-1, GP73-siRNA-1+ pcDNA-GP73, WT1-siRNA and WT1-siRNA + GP73-siRNA-1 groups. Expressions of GP73, TGF-β1, Smad2, p-Smad2, E-cadherin and vimentin were detected using RT-qPCR and Western blotting. Cell proliferation, migration and invasion were determined using MTT assay, scratch testing and Transwell assay, respectively. Compared with the blank and NC groups, levels of GP73, TGF-β1, Smad2, p-Smad2, N-cadherin and vimentin decreased, and levels of WT1 and E-cadherin increased in the GP73-siRNA-1 and GP73-siRNA-2 groups, while the opposite results were observed in the WT1 siRNA, TGF-β, TSP-1 and TGF-β + TSP-1 groups. Cell proliferation, migration and invasion notably decreased in the GP73-siRNA-1 and GP73-siRNA-2 groups in comparison with the blank and NC groups, while in the WT1 siRNA, TGF-β, TSP-1 and TGF-β + TSP-1 groups, cell migration, invasion and proliferation showed the reduction after the EMT. These results suggest that GP73 promotes bladder cancer invasion and metastasis by inducing the EMT through down-regulating WT1 levels and activating the TGF-β1/Smad2 signalling pathway.

Report of a human autopsy case in maxillary sinuses augmented using a synthetic bone substitute: Micro-computed tomographic and histologic observations.

This study of a human autopsy case aimed to characterize the histologic and micro-computed tomographic results of maxillary sinus augmentation using a synthetic bone substitute and simultaneous implant placement at 6 years.

Positive Correlation between Matrix Metalloproteinases and Epithelial-to-Mesenchymal Transition and its Association with Clinical Outcome in Bladder Cancer Patients.

Involvement of matrix metalloproteinases (MMPs) in the pathogenesis of urothelial carcinoma elects them to be sensitive marker for clinical and prognostic implications. MMPs regulate tumor growth and invasion by inducing epithelial-to-mesenchymal transition (EMT) which is characterized by the complex reprogramming of epithelial cells and ultimately bring about major changes in the structural organization of bladder urothelium. The present study has been undertaken to evaluate the clinical relevance of MMPs in two distinct types of bladder cancer disease. Expression analysis of MMPs namely MMP-2, MMP-7, MMP-9 and EMT markers including epithelial marker, E-cadherin; mesenchymal markers, N-cadherin and Vimentin; and EMT-activating transcriptional factors (EMT-ATFs), Snail, Slug, Twist and Zeb was done in 64 cases of bladder tumor tissues [{Non-muscle invasive bladder cancer (NMIBC): 35 cases} and {Muscle invasive bladder cancer (MIBC): 29 cases}] by real-time quantitative polymerase chain reaction (RT-qPCR). Immunohistochemistry (IHC) staining was done in matched bladder tumor tissues to evaluate the protein expression and localization of E-cadherin, N-cadherin, Vimentin, Snail, and Slug. Our data showed overexpression of MMP-2, MMP-7 and MMP-9 at transcriptome level in 32.8%, 25% and 37.5% bladder tumor cases respectively. These tumor tissues were examined for higher expression of mesenchymal markers (N-cadherin and Vimentin) at mRNA and protein level and exhibited statistical association with tumor stage and tumor grade (p = 0.02, p = 0.04, Mann-Whitney test). Significant statistical correlation in tumor tissues with overexpressed MMPs has also been observed between gain of transcriptional factors and weak expression of E-cadherin with tumor stage, grade, gender, presence of hematuria and smoking history of the patients. Gene expression patterns of EMT markers in bladder tumors with overexpressed MMPs and their significant association with clinical profile validate the important role of MMPs in the pathogenesis of urothelial carcinoma of bladder (UCB). Increased expression of specific MMPs may affect several downstream EMT programs and thus may improve its diagnostic and prognostic utility in clinical setting.

The systemic inflammation-based Glasgow Prognostic Score as a powerful prognostic factor in patients with upper tract urothelial carcinoma.

The combination of C-reactive protein and albumin, the Glasgow Prognostic Score (GPS), had independent prognostic value in patients with varying cancers, except for upper tract urothelial carcinoma (UTUC). The aim of this study was to describe the relationship between GPS and survival in patients with UTUC after adjustment for other prognostic factors.