BCG is currently the most effective intravesical agent for the treatment and prophylaxis of superficial bladder cancer. BCG is recognized as a nonspecific immune stimulant. Intravesical BCG induces inflammation of the bladder with infiltration of a broad range of cell types. BCG may activate macrophages, T lymphocytes, B lymphocytes, natural killer cells (NK), and killer cells. 40 Intravesical BCG immunotherapy results in cytokine production, including interleukins 1(IL-1), 2(IL-2), and 6(IL-6), interferon gamma, and tumor necrosis factor alpha (TNF-a) 41 which can be measured in the urine for many hours after instillation. McAveray et al. 42 reported that BCG induces a local Type II immunologic response which may be mediated by Interleukin (IL) 4; IL-4, IL-10, the later cytokines may suppress cell- mediated responses. These cytokines also cause a shift to Type I response with the subsequent development of a protective antitumor response.
77 Read more
A total of 90 cases of patients with superficial bladder cancer treated in our hospital from Jan2011 to Jun2016 were collected. The 90 patients were randomly divided to be control group and combination group, 45 cases for each. In control group, there were 35 male cases and 10 female cases; Ages were ranged from 50-70 years old, the average age was 60 years old; Tumor diameters were ranged from 0.5-3.0 cm, the average diameter was (1.8±0.3) cm. Patients were divided by WHO tumor classification as 8 cases of class G1, 22 cases of class G2 and 15 cases of class G3; For tumor positions, there were 4 cases on anterior wall of bladder, 20 cases on side wall of bladder, 6 cases on floor of bladder, 12 cases on triangle of bladder and 3 cases on neck of bladder; In combination group, there were 33 male cases and 12 female cases; Ages were ranged from 50-70 years old, the average age was 61 years old; Tumor diameters were ranged from 0.5-3 cm, the average diameter was (1.9±0.4) cm. Patients were divided by WHO tumor classification as 9 cases of class G1, 23 cases of class G2 and 15 cases of class G3; For tumor positions, there were 4 cases on anterior wall of bladder, 19 cases on side wall of bladder, 7 cases on floor of bladder, 11 cases on triangle of bladder and 4 cases on neck of bladder. No obvious difference showed on ages, genders, tumor sizes or physical conditions between two groups of patients ( P >0.05).
as well as cancer cell invasion and migration in bladder cancer tissue, and they can be secreted into the blood circulation by tumor lesions and then become the marker molecules reflecting tumor load [12-14] . VEGF is the currently known cytokine with the most powerful angiogenesis-promoting effect, and it can induce endothelial cells to form blood vessel-like structures; FGF includes two different subtypes, αFGF and 毬 FGF, and they have promoting effect on endothelial cell migration and proliferation, and also have promoting effect on angiogenesis. MMP2 and MMP9 are two kinds of collagenase in matrix metalloproteinase family, have specific hydrolysis effect on type IV collagen in extracellular matrix, and can promote cancer cells to break through the limit of local basement membrane, infiltrate towards the surrounding and transfer to the distant. In the study, analysis of the serum levels of above marker molecules between the two groups of patients 1 year after operation showed that serum VEGF, αFGF, 毬 FGF, MMP2 and MMP9 levels of combined group were significantly lower than those of routine group. This means that combined use of oral administration of Shiquandabu pill can reduce the postoperative tumor load and inhibit angiogenesis and cell invasion in patients with bladder cancer. In recent years, the studies about the postoperative recurrence of superficial bladder cancer believe that the tumor stem cells in local lesion tissue are the pathological basis of tumor recurrence. Bladder cancer stem cells are a special type of cell mass with multi-directional differentiation potential in bladder tissue and are regarded as initiating cells of the occurrence and recurrence of bladder cancer, and the residual bladder cancer stem cells after transurethral resection of bladder tumor can induce tumor formation. ALDH1, Sox2, Nanog, CD47 and CD133 are the marker molecules on bladder cancer stem cell surface [15,16] . ALDH1
Although thorough endoscopic tumor resection remains the principal treatment, intravesical agents have become an important in the subgroup of tumors that are at risk of progression. Intravesical Bacillus Calmette-Guerin, is effective treatment in preventing recurrences & delaying progression in superficial bladder cancer. It has been in use since the 1980's, and is the most proven and effective form of immunotherapy. Though therapy with BCG is generally safe, it is not completely, without side effects.
76 Read more
To model in vivo human SBC, a rat orthotopic bladder tumour model was used that was previously described by Xiao et al (1999). AY-27 cells are a rat bladder transitional cell carcinoma cell line, which was established as a primary bladder tumour in Fischer f344 rats, which were feed FANFT (N(4-(5-Nitro-2-Furyl)-2-Thiazolyl Formamide) (Xiao et al, 1999). Histological examination of the in vitro and in vivo tumour specimens confirmed the presence of grade II-III transitional cell carcinoma (Xiao et al, 1999). AY-27 cells, which were previously tested for susceptibility for HSV replication were used in this model. AY-27 cells were stably transfected with the herpes virus entry receptor (HVEM) and a clone selected that supported infection with HSV. Fusion assay results showed a reduction in metabolic enzyme activity of up to 30% (MTS assay) in AY-27 HVEM cells infected with Oncovex GALV/CD compared with the Oncovex GFP control (Supple- mentary Figure S1). This is in addition to the cytotoxcity seen with HSV replication alone. AY-27 HVEM cells were further tested in our prodrug assay, which showed that Oncovex GALV/CD can meta- bolise 5-FC within these cells, resulting in a decrease in metabolic enzyme activity of up to 81% (MTS assay) when compared with controls (Supplementary Figure S1). To facilitate tumour seeding, the bladder mucosa was conditioned with an acid rinse followed by neutralisation with alkali. After tumour seeding, a high success rate of implantation was seen (495%). Figure 5D shows an example of such an in vivo experiment (without treatment) where tumours were seeded and the bladder removed at necropsy after 18 days. The first three bladders showed a high tumour load (Figures 5D, 1, 2 and 3). The fourth bladder was a control in which bladder mucosa was conditioned (acid/alkali rinse) but no cells were seeded (Figure 5D, 4). The tumour implantation procedure was well tolerated by the animals. To study the effects of Oncovex GALV/CD in vivo, freshly
12 Read more
Study participants did not know the results of the NMP22 assay until after all 100 consecutive patients had been enrolled. After complete enrolment, retrospective chart reviews were undertaken documenting events from the time of diagnosis of the patient’s highest grade/stage tumour to the most recent follow-up. All patients had been followed for at least 6 months. Data were collected on presenting symptoms, bladder cancer history, tumour recurrence, pro- gression and disease-related death. Patients who had a pos- itive cystoscopy or malignant tumour on pathological exam- ination after the enrolment routine surveillance were said to have recurred. Patients who demonstrated higher-stage and/or grade disease than was previously documented were identified to have disease progression. Follow-up was doc- umented as the time from the previous highest stage/grade tumour to recurrence, progression, death or most recent follow-up.
intravesical administration might be the most convenient clinical application to ensure maximal delivery of therapeu- tic agents at the site of the disease, to improve efficacy, and to minimize systemic side effects of antineoplastic agents. However, short dwelling time of drugs in the bladder and the low drug permeability of urothelium are the main fac- tors that limit the success of the treatment. The efficacy of intravesical treatment might be increased by prolonging the residence time of the drug inside the bladder. By this way, drugs can attach to the urinary bladder wall and penetrate it for extended periods. For these reasons, the present study describes the preparation of mucoadhesive Gem-HCl-loaded MSs to provide a sustained-release profile, prolong residence time, and enhance efficiency for bladder cancer. In addition, MSs were dispersed in mucoadhesive Chi or in situ Plx gels for intravesical administration and comprehensive in vitro/ ex vivo/in vivo evaluations performed.
17 Read more
Patients were followed up every 3 months with urine cy- tology and cystoscopy during the first year, every 6 months for the next 2 years, and then yearly thereafter. Ultrasonog- raphy, CT scanning, cystoscopy and urinary cytology were used to evaluate recurrence. Recurrence was defined as the occurrence of a new tumor in the bladder. Progression was defined as confirmed tumor invading muscular layer. Treat- ment failure was defined as need for radical cystectomy (RC), systemic chemotherapy and radiation therapy.
In our study, the low recurrence incidence after adjuvant mistletoe extract treatment is encouraging and is not the result of patient selection, since the study patients and the local historical controls are comparable with respect to staging and grading. Further studies may help to find the optimal dose and confirm the role of standardized mistletoe in patients with superficial bladder cancer.
The wall of the bladder is lined with cells called transitional cells and squamous cells. Studies performed by The National Cancer Institute found that more than 90 percent of bladder cancers originate in the transitional cells. This type of bladder cancer is called transitional cell carcinoma. Squamous cell carcinoma accounts for eight percent of bladder cancer patients. When cancer is found only in the lining of the bladder, it is called superficial bladder cancer. Physicians often call this carcinoma in situ. This type of bladder cancer will often come back after treatment. If this happens, the disease most often recurs as another superficial cancer in the bladder. In this type of cancer the superficial tumor may grow through the lining and into the muscular wall of the bladder.
of dynamic contrast enhanced (DCE)-MRI is a useful technique in which rapid enhancement of tumour by uptake of the contrast agent is compared to bladder wall, assisting in differentiating tumour from surrounding normal tissue. Buy et al., investigated MRI staging of bladder carcinoma and its correlation with pathologic findings and concluded that MRI showed detection of bladder tumour invasion into adjacent organs better than CT scan . Studying method of DCE-MRI for staging of superficial bladder cancer, Scattoni et al., found that contrast enhancement increased the accuracy of the method in superficial cancer staging . Having observed high temporal resolution of the method of DCE-MRI, Barentsz et al., concluded that use of this method to distinguishing between after-biopsy effects and malignancy was possible . Tekes et al., evaluated the accuracy of dynamic MRI staging of bladder and observed that the accuracy of dynamic MRI staging was high in differentiating superficial tumours from invasive tumours and organ- confined tumours from non-organ-confined tumours of bladder . Daneshmand et al., in a retrospective study on staging of invasive bladder cancer reported improvement of staging of tumours and lymph nodes by DCE-MRI . In a study conducted by Ghafoori et al., MRI was reported as a reliable method with high accuracy in bladder cancer staging .
In order to knock-down the expression of C14orf166, two C14orf166 siRNAs and their cognate control siR- NAs (Scramble) were synthesized by Guangzhou RiboBio Co (Guangdong, China). 20 nm siRNA were transfected into indicated cells in six plates using Lipofectamine RNAiMax Reagent (Life Technologies) according to the manufacturer’s instruction. Total RNA from cultured cells and surgical fresh bladder tumor tissues and adja- cent bladder tissues were extracted using Trizol (Life technologies) according to manufacturer’s instructions. cDNA was synthesized from total RNA using ReverTra Ace qPCR RT Kit (TOYOBO). Relative expressions of different genes were detected using SYBR Green PCR Kit (Roche) with the GAPDH gene as an internal reference. The PCR reactions were run using ABI 7500 Real- time PCR System. The comparative C t method (ΔΔC t ) was
10 Read more
In the present study, we reported and validated that P3H4 was significantly upregulated in primary tumor compared with their paired adjacent normal tissues in 44 patients with bladder cancer. The differential expression of P3H4 was further confirmed in the TCGA cohort of a large sample size. Furthermore, high P3H4 expression was found to be closely related to several aggressive clinico- pathological factors, such as advanced AJCC stage. More- over, Kaplan–Meier analysis found that the low P3H4 expression group had a better prognosis than the high P3H4 expression group. Univariate and multivariate Cox regression analyses revealed that P3H4 was an independ- ent predictor of poor OS in bladder cancer. Taken to- gether, our findings suggest that P3H4 is involved in the progression of bladder cancer. A systematic literature re- view revealed that this was the first description of the rela- tionship between P3H4 and bladder cancer.
Nowadays, bladder cancer is the fourth most common cancer in adults and the second most frequent urogenital tumor. Predicting recurrence and pro- gression of superficial bladder tumors, with available clinical information to decide the therapy to be used is a difficult task. In this work, two mathemati- cal models were developed to help specialists on the decision process. The mathematical tool used to formulate the model was the fuzzy sets theory, due to its capacity in dealing with uncertainties inherent in medical concepts. In the first model, Stage, Grade and Size of the tumor were also considered input variables and Risk of Recurrence of a superficial bladder tumor as output va- riable of the first Fuzzy Rule-Based Systems (FRBS). In the second model, in addition to the Stage, Grade and Size of the tumor, it was also considered as input variable of a second FRBS Carcinoma in situ and, the Risk of Progres- sion of superficial tumors as an output variable. For each model, simulations were made with data originated from of patients of the Clinics Hospit- al/UNICAMP and A. C. Camargo Hospital of São Paulo, with the aim to ve- rify the reliability of results generated by the two systems. From a database and the possibility found by FRBS, after the possibility-probability transfor- mation, we can generate the real probability of each fuzzy output set.
13 Read more
The highest levels of fluorescence seen were several times greater than those achieved after IV administration but in all of the 12 bladders examined there were large areas of minimal or zero uptake. Interestingly there did not appear to be any clear correlation between fluorescence distribution or intensity and either the concentration of sensitiser instilled or whether it was left in contact with the urothelium for 30 min or 1 h. The AlSPc mixture used is a relatively hydrophilic molecule due to the large predominance of the trisulphonated fraction, but it would be expected that the uptake of the purified disulphonated derivative (AlPcS2), which is more lipid soluble, might be more effective. AlPcS2, administered in equimolar concentrations to the AlSPc mixture, did appear to be taken up much more evenly than the mixture in the most superficial layers of the bladder wall. Although this uptake was considerably more uniform than that seen with the mixture there were still a few areas where only minimal uptake was apparent so no figures for fluorescence intensity will be given. Of more interest, however, was the observation that in none of the 12 bladders examined was there any major fluorescence from the muscle layer In most cases the signal from the muscle hardly exceeded the background intensity (fig. 6.10). This produced an extremely high ratio of fluorescence intensities between the superficial and deep layers, much greater than that seen after intravenous administration and often in the order of 20:1. The graph superimposed on fig. 6.10 demonstrates this very strong, localised uptake in a typical specimen.
393 Read more
Bladder cancer is a common disease that is often detected late and has a high rate of recurrence and progression. The current standard of care for the primary detection and follow-up of NMIBC consists of urethro-cystoscopy associated with cytology. However, several clinical risk factors have been claimed to predict recurrence and progression, these factors have a predictive value on a population basis, but no parameter has been found that reliably predicts how an in- dividual patient’s tumor will behave. In the last years many markers have been described in order to decrease the num- ber of cystoscopies and try to provide individualized risk-stratified decision-making. We have focused our review in tumor markers for primary diagnosis, surveillance of non-muscle-invasive bladder cancer, and predicting progression to muscle-invasive disease. After our review, we can conclude that to the date no non-invasive biomarker has proven to be sensitive and specific enough to replace cystoscopy, neither in the diagnosis nor in the follow-up. On the other hand, promising results have been reported of potential biomarkers for predicting recurrence, early progression and poor re- sponse to BCG, new studies should be promoted to validate these results and make possible to incorporate markers as a new tool in clinical guidelines.
Bladder cancer remains one of the most com- mon cancers worldwide, especially in elderly men [1, 2]. Bladder cancer is classified as non- muscle invasive and muscle-invasive cancers. The majority of bladder cancers are non-mus- cle-invasive ones and limited to the mucosa or submucosa when they are diagnosed . Although through the combined therapyap- proaches, bladder canceris still high risk for its characteristics of high rate of recurrence and mortality . Therefore, earlier diagnosis, aggressive radical surgery and adjuvant mul- timodal treatment are needed for survival improvement. Some parameters are used to predict the clinical outcome and treatment response, among which cystoscopy is an effec- tive way to diagnose this cancer. However, these parameters are limited for a risk of some complications . Recently, various molecular
The role of FGFR inhibitors in the treatment of advanced bladder cancer is not yet clear and awaits the results of early clinical trials. Interestingly, a recent study of the relationship of FGFR3 mutation and expression status to outcome in muscle-invasive bladder cancer treated by cystectomy with or without adjuvant cisplatin-gemcitabine chemotherapy, reported FGFR3 over-expression to be an independent predictor of reduced OS and RFS. 19 The present study did not reveal the same relationship. The reason for this is unclear, but this potential relationship should be examined in a much larger series of patients to clarify the situation as such a relationship could have major predictive application.
17 Read more
Lack of patient referral from urology to MO (social and professional role) was cited as a main barrier to providing the chemotherapy treatment. Other barriers to treating patients included uncertainty about which patients derive benefit from chemotherapy (knowledge), a perceived lack of skills in the subtleties of bladder cancer treatment (skills), lack of confidence that the survival benefit of NACT/ACT is clinically important (beliefs about consequences), lack of urology presence at multidisciplinary case conferences (environmental context and resources) and a lack of organizational clarity regarding the referral process (environmental context and resources) (Figure 3).
19 Read more
The prognosis for muscle-invasive bladder cancer in patients with an early-stage disease and negative lymph nodes is good; thus, early cystectomy for low-stage tumors will give excellent results. However, non-muscle-invasive bladder cancer is not subjected to radical cystectomy but to the more conservative transurethral resection and intravesical chemotherapy or immunotherapy. Following the European Association of Urology (EAU) guidelines, T1 tumors invading the stroma and those at high risk of progression (eg, high grade, multifocality, carcinoma in situ, and large tumor size), and all T1 tumors failing intravesical therapy are considered for early cystectomy. 1 Additionally, some patients with extensive papillary tumors that cannot