scholarly journals The Antitumor Effects of Plasma-Activated Saline on Muscle-Invasive Bladder Cancer Cells In Vitro and In Vivo Demonstrate Its Feasibility as a Potential Therapeutic Approach

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1042
Author(s):  
Hao Zhang ◽  
Jishen Zhang ◽  
Bo Guo ◽  
Hailan Chen ◽  
Dehui Xu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Culture Media ◽  
Invasive Bladder Cancer ◽  
Antitumor Effects ◽  
Muscle Invasive Bladder Cancer ◽  
Plasma Irradiation ◽  
Muscle Invasive

Muscle-invasive bladder cancer (MIBC) is a fast-growing and aggressive malignant tumor in urinary system. Since chemotherapy and immunotherapy are only useable with a few MIBC patients, the clinical treatment of MIBC still faces challenges. Here, we examined the feasibility of plasma-activated saline (PAS) as a fledgling therapeutic strategy for MIBC treatment. Our data showed that plasma irradiation could generate a variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in saline. In vivo tests revealed that pericarcinomatous tissue injection with PAS was effective at preventing subcutaneous bladder tumor growth, with no side effects to the visceral organs after long-term administration, as well as having no obvious influence on the various biochemistry indices of the blood in mice. The in vitro studies indicated that adding 30% PAS in cell culture media causes oxidative damage to the bladder transitional cells T24 and J82 through enhancing the intracellular ROS level, and eventually induces cancer cells’ apoptosis by activating the ROS-mediated Fas/CD95 pathway. Therefore, for an intracavity tumor, these initial observations suggest that the soaking of the tumor tissue with PAS by intravesical perfusion may be a novel treatment option for bladder cancer.

Pembrolizumab and chemoradiotherapy for muscle invasive bladder cancer: The ANZUP 1502 PCR-MIB trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS531-TPS531 ◽  
Author(s):  
Andrew James Weickhardt ◽  
Farshad Foroudi ◽  
Shomik Sengupta ◽  
Laura Galletta ◽  
Alan Herschtal ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Genetic ◽  
Response To Therapy ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
Immunological Parameters ◽  
Muscle Invasive

TPS531 Background: Pembrolizumab leads to responses in ~20% of metastatic bladder cancer patients. Irradiation of bladder cancer cells in-vitro and in-vivo leads to upregulation of PD-L1, and in immunocompetent mouse models blockade of PD-L1 leads to delayed tumour growth following irradiation. Randomised data from PACIFIC trial in NSCLC shows the addition of PD-L1 inhibition to chemoradiation significantly prolongs PFS. A trial of chemoradiotherapy with pembrolizumab will assess safety and synergy of the combination in localised bladder cancer. Methods: This pilot study enrols patients with maximally resected non-metastatic muscle invasive bladder cancer, who either wish for bladder preservation or are ineligible for cystectomy. This study will assess the safety and feasibility of combining pembrolizumab with chemoradiotherapy in ECOG 0-1 patients without contraindications to pembrolizumab. The study has enrolled 4 of a planned 30 patients. All patients treated with 64Gy of radiation therapy in 32 fractions over 6 weeks, 2 days. Cisplatin 35mg/m2 IV concurrently weekly for 6 doses with radiation. Pembrolizumab commences concurrently with radiation and is given 200mg IV q21 days for 7 doses. Surveillance cystoscopy is performed 12 & 24 weeks after the commencement of chemoradiotherapy to assess response to therapy. Patients will enter follow up with clinical assessment, cystoscopy and CT staging performed at intervals until close of study. The primary endpoint assessed will be safety, as defined by a satisfactorily low rate of unacceptable toxicity (G3-4 adverse events or failure of completion of planned chemotherapy and radiotherapy according to defined parameters). The secondary endpoint will be efficacy, as assessed by the proportion of patients achieving a best response of complete response based on the first two 12 and 24 week post chemoradiotherapy cystoscopic assessments. Exploratory analysis will include assessment of tumour histopathological, molecular, genetic and immunological parameters. It is expected that it will take two years to accrue the 30 patients across 5 Australian centres. NCT02662062. Clinical trial information: NCT02662062.

scholarly journals In vivo Evaluation of Mucoadhesive Nanoparticulate Docetaxel for Intravesical Treatment of Non–Muscle-Invasive Bladder Cancer

2011 ◽  
Vol 17 (9) ◽  
pp. 2788-2798 ◽  
Author(s):  
Clement Mugabe ◽  
Yoshiyuki Matsui ◽  
Alan I. So ◽  
Martin E. Gleave ◽  
Jennifer H. E. Baker ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
In Vivo Evaluation ◽  
Intravesical Treatment ◽  
Muscle Invasive

Role of heat shock protein 90 inhibition with 17-(allylamino)-17 (demethoxygeldenamycin) in muscle-invasive bladder cancer cells.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 273-273
Author(s):  
H. Williams
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Intracellular Signaling ◽  
Heat Shock Protein 90 ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Cancer Cells ◽  
Muscle Invasive

273 Background: Muscle invasive bladder cancer portends a poor long term prognosis. Platinum based therapy is the mainstay of treatment but more effective agents are needed for management of this disease. Heat shock protein 90 (Hsp90) is a ubiquitous protein that has been shown to be overexpressed in tumor cells. It functions as a molecular chaperone responsible for the stability and function of a number of proteins critical to the oncogenic process. 17-(allylamino)-17 demethoxygeldanamycin (17 AAG) is a Hsp90 inhibitor that is currently in phase III trials in several tumor models. The purpose of this study was to evaluate the role of 17 AAG treatment for bladder cancer in vitro. Methods: Seven bladder cancer cell lines representing muscle invasive bladder cancer were treated in the presence and absence of 17 AAG. Both short term and long term treatments were evaluated for their effects on growth, motility and invasion of the cancer cells. Expression of proteins involved in cell growth, survival and metastasis were evaluated with Western blotting. Results: Our data demonstrated that 17 AAG treatment resulted in induction of apoptosis, inhibition of cell cycle progression through inhibition of MAP kinase pathway and cyclin D1 expression. Decreased tumor cell motility and invasion was observed with 17 AAG treatment. Several intracellular signaling pathways involved in cell proliferation, invasion and metastasis were inhibited. Conclusions: Hsp90 inhibition in muscle invasive bladder cancer cells impacts growth, motility and invasiveness by inhibiting numerous intracellular signaling pathways. Taken together, these findings suggest a possible role for Hsp90 inhibitors in bladder cancer tumorigenesis. No significant financial relationships to disclose.

Evans blue as a selective dye marker for white-light diagnosis of non-muscle-invasive bladder cancer: an in vitro study

2011 ◽  
Vol 109 (2) ◽  
pp. 300-305 ◽  
Author(s):  
Mieke Roelants ◽  
Ann Huygens ◽  
Ivo Crnolatac ◽  
Ben Van Cleynenbreugel ◽  
Evelyne Lerut ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
White Light ◽  
Evans Blue ◽  
In Vitro Study ◽  
Vitro Study ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Impact of angiotensin inhibitors on pathologic complete response with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 432-432
Author(s):  
Jonathan Thomas ◽  
Gregory Russell Pond ◽  
Catherine Curran ◽  
Dory Freeman ◽  
Praful Ravi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Angiotensin Receptor Blockers ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Invasive Bladder Cancer ◽  
Antitumor Effects ◽  
Muscle Invasive Bladder Cancer ◽  
Pathologic Features ◽  
Muscle Invasive

432 Background: The renin-angiotensin system (RAS) is involved in regulation of angiogenesis, cell proliferation, desmoplasia and immunosuppression. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) may have antitumor effects partly by inhibiting transforming growth factor (TGF)-β, a major resistance mechanism in bladder cancer. Methods: Patients (pts) with muscle invasive bladder cancer (MIBC) treated or not treated with ACEi/ARB while receiving preceding radical cystectomy (RC) were assessed for pathologic complete response (pCR) defined as pT0N0 and overall survival (OS). Pathologic features, performance status, clinical stage, type and number of cycles of NAC, and presence of grade ≥3 toxicities were collected retrospectively. The Kaplan-Meier method was used to estimate overall survival (OS). Logistic and Cox regression was used to explore factors potentially prognostic for pCR and OS respectively. Results: 187 patients received NAC followed by RC. The mean age at the time of NAC was 65. 71% were male and 29% were female. Of the 187 patients, 61% received Cisplatin/Gemcitabine and 28.3% received dose dense MVAC. Of patients receiving NAC, 53 (28%) had a pCR. The 5-year OS was 64%. There were 41 (21.9%) patients taking an ACEi and 24 (12.8%) patients taking an ARB at the start of NAC. Of the 41 patients who took an ACEi, 17 (41.5%) had a pCR; of the 146 patients who did not take an ACEi, 36 (24.7%) had a pCR. ACEi intake during NAC was the only factor associated with pCR on multivariable analysis (odds ratio of 2.17 [95% CI 1.05-4.48] p = 0.037). pCR was the only factor shown to be associated with significantly improved OS (Hazard Ratio 0.18 [95% CI 0.07-0.45] p = < 0.001). After adjusting for pCR, ACEi was not significantly prognostic of OS (HR = 1.12, 95% CI = 0.60 to 2.09, p = 0.72). ARB intake while receiving NAC was not associated with pCR or OS. Conclusions: ACEi intake was associated with significantly increased pCR in patients with MIBC receiving NAC, and pCR was the only significant factor associated with OS. We hypothesize that ACEi may augment the activity of NAC and increase pCR, which translates to improved OS. ACEi intake was not associated with improvement in OS potentially due to competing causes of mortality in patients requiring ACEi. Our data requires validation.

Therapy for Non-Muscle Invasive Bladder Cancer: HP-NAP

2012 ◽  
Vol 79 (2) ◽  
pp. 142-148 ◽  
Author(s):  
Daniele D'Agostino ◽  
Marco Racioppi ◽  
Alessio Filianoti ◽  
Luca Di Gianfrancesco ◽  
Gaia Codolo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Recurrence ◽  
New Drugs ◽  
In Vivo Studies ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Ifn Γ ◽  
Muscle Invasive ◽  
Bladder Cancer Recurrence

Purpose Patients with non-muscle invasive bladder cancer recurrence after 2 induction courses of BCG are eligible for radical cystectomy. So, in the last years research to discover new drugs for the management of non-muscle invasive bladder cancer recurrence after failure of first and second line therapy is ongoing. In accordance to the results obtained with BCG, whose mechanism depends on the induction of the T helper 1 (TH1) immune response, we investigated the activity of a Toll-like receptor (TLR) 2 ligand, named Helicobacter Pylori Neutrophil Activating Protein (HP-NAP), that we recently demonstrated being able of enhancing the differentiation of Th1 cells, both in vitro and in vivo, because of its ability to create an IL-12 enriched milieu. Materials and Methods We show here, in a mouse model of bladder neoplasm implants, that local administration of HP-NAP decreases tumor growth by inducing tumor necrosis. Results The result is joined up with a massive cluster of both CD4+ and CD8+ IFN-γ+ cells, within neoplasm and regional lymph nodes. It is of note that HP-NAP-treated tumors show also a reduced vascularization due to the anti-angiogenic activity of IFN-γ induced by HP-NAP. Conclusions The present study suggests that the activity of HP-NAP against urothelial tumor burden warrants subsequent in vivo studies.

scholarly journals Nanaomycin K inhibited epithelial mesenchymal transition and tumor growth in bladder cancer cells in vitro and in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Koichi Kitagawa ◽  
Katsumi Shigemura ◽  
Aya Ishii ◽  
Takuji Nakashima ◽  
Hirotaka Matsuo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Bladder Cancer Cells ◽  
And Migration ◽  
Muscle Invasive

AbstractNanaomycin K, derived from Streptomyces rosa subsp. notoensis OS-3966T, has been discovered to have inhibitory bioactivity on epithelial–mesenchymal transition (EMT), an important mechanism of cancer cell invasion and migration. In this study, we examined the anti-EMT and anti-tumor effect of nanaomycin K in bladder cancer, where EMT has important roles in progression. We treated two bladder cancer lines, non-muscle-invasive KK47 and muscle-invasive T24, with nanaomycin K to determine the effects on cell proliferation, apoptosis and expression of EMT markers in vitro. Wound-healing assays were performed to assess cell invasion and migration. We conducted an in vivo xenograft study in which mice were inoculated with bladder cancer cells and treated with intratumoral administration of nanaomycin K to investigate its anti-tumor and EMT inhibition effects. As the results, nanaomycin K (50 µg/mL) significantly inhibited cell proliferation in KK47 (p < 0.01) and T24 (p < 0.01) in the presence of TGF-β, which is an EMT-inducer. Nanaomycin K (50 µg/mL) also significantly inhibited cell migration in KK47 (p < 0.01) and T24 (p < 0.01), and induced apoptosis in both cell lines in the presence of TGF-β (p < 0.01). Nanaomycin K increased the expression of E-cadherin and inhibited the expression of N-cadherin and vimentin in both cell lines. Nanaomycin K also decreased expression of Snail, Slug, phospho-p38 and phospho-SAPK/JNK especially in T24. Intratumoral administration of nanaomycin K significantly inhibited tumor growth in both KK47 and T24 cells at high dose (1.0 mg/body) (p = 0.009 and p = 0.003, respectively) with no obvious adverse events. In addition, nanaomycin K reversed EMT and significantly inhibited the expression of Ki-67 especially in T24. In conclusion, we demonstrated that nanaomycin K had significant anti-EMT and anti-tumor effects in bladder cancer cells, suggesting that nanaomycin K may be a therapeutic candidate for bladder cancer treatment.

scholarly journals Prognostic Value of BUB1 for Predicting Non-Muscle-Invasive Bladder Cancer Progression

2021 ◽  
Vol 22 (23) ◽  
pp. 12756
Author(s):  
Xuan-Mei Piao ◽  
Chaelin You ◽  
Young Joon Byun ◽  
Ho Won Kang ◽  
Junho Noh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Mitotic Checkpoint ◽  
Invasive Bladder Cancer ◽  
Common Disease ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Cancer Cells ◽  
Muscle Invasive ◽  
Normal Controls

Non-muscle-invasive bladder cancer (NMIBC) is a common disease with a high recurrence rate requiring lifetime surveillance. Although NMIBC is not life-threatening, it can progress to muscle-invasive bladder cancer (MIBC), a lethal form of the disease. The management of the two diseases differs, and patients with MIBC require aggressive treatments such as chemotherapy and radical cystectomy. NMIBC patients at a high risk of progression benefit from early immediate cystectomy. Thus, identifying concordant markers for accurate risk stratification is critical to predict the prognosis of NMIBC. Candidate genetic biomarkers associated with NMIBC prognosis were screened by RNA-sequencing of 24 tissue samples, including 16 NMIBC and eight normal controls, and by microarray analysis (GSE13507). Lastly, we selected and investigated a mitotic checkpoint serine/threonine kinase, BUB1, that regulates chromosome segregation during the cell cycle. BUB1 gene expression was tested in 86 NMIBC samples and 15 controls by real-time qPCR. The performance of BUB1 as a prognostic biomarker for NMIBC was validated in the internal Chungbuk cohort (GSE13507) and the external UROMOL cohort (E-MTAB-4321). BUB1 expression was higher in NMIBC patients than in normal controls (p < 0.05), and the overexpression of BUB1 was correlated with NMIBC progression (log-rank test, p = 0.007). In in vitro analyses, BUB1 promoted the proliferation of bladder cancer cells by accelerating the G2/M transition of the cell cycle. Conclusively, BUB1 modulates the G2/M transition to promote the proliferation of bladder cancer cells, suggesting that it could serve as a prognostic marker in NMIBC.

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