Inhibition of Bladder Carcinoma Cell Adhesion by Oligopeptide Combinations in Vitro and in Vivo

Böhle, Andreas; Jurczok, A.; Ardelt, Peter; Wulf, Tina; Ulmer, Artur J.; Jocham, Dieter; Brandau, Sven

doi:10.1016/s0022-5347(05)65468-7

Cited by 27 publications

(19 citation statements)

References 50 publications

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“…Both the α3β1 and α5β1 integrin family members may be of particular relevance in the context of re-seeding of tumor cells post-TURBT in NMIBC. In addition to the efficacy results shown here, the notion that integrins mediate UCC seeding is further supported by earlier work where α5β1-specific and α3β1-specific ECM-blocking oligopeptides used in combination were able to effectively inhibit orthotopic MB49 tumor implantation (11) and in another more recent report where shRNA knockdown of α3 resulted in impaired establishment of human T24 UCCs in a subcutaneous xenograft model (13).…”

Section: Discussionsupporting

confidence: 83%

“…Re-seeding may be facilitated, in part, by the interaction of tumor cell integrins with extracellular matrix (ECM) components including fibronectin, laminin, and collagen, all of which are likely to be exposed at the surgical site following resection. Previous reports have indicated that specific mammalian integrins, particularly integrin heterodimer family members alpha3beta1 (α3β1) and alpha5beta1 (α5β1), are implicated as being required for the attachment of tumor cells to the ECM and establishment of tumors in the urothelium in vivo (11)(12)(13).…”

Section: Been Previously Characterized As An Integrin-specific Oncolymentioning

confidence: 99%

“…The anti-implantation variation of the MB49 model serves as a surrogate for the immediate postoperative treatment of NMIBC and can be useful in the pharmacological assessment of agents being investigated for this purpose (11,14). Characterized in an earlier report under the research name VAX-IP, VAX014 recombinant Escherichia coli bacterial minicells (VAX014 hereafter) have been engineered to express invasin from Yersinia pseudotuberculosis to selectively target and deliver a novel bacterial protein toxin, perfringolysin O (PFO), to human and murine urothelial carcinoma cells (UCCs) expressing α3β1 or α5β1 (15).…”

Section: Been Previously Characterized As An Integrin-specific Oncolymentioning

confidence: 99%

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A Single Intravesical Instillation of VAX014 Inhibits Orthotopic Superficial Bladder Tumor Implantation to Increase Survival

Hancock

McGuire

Tsuji

et al. 2016

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Abstract. Background/Aim: VAX014 minicells (VAX014) Bladder cancer ranks second amongst newly diagnosed urothelial carcinomas worldwide, is the sixth leading cause of cancer death and the fourth most common malignancy of men in developed countries (1). Current estimates suggest that as many as 75-80% of patients with bladder cancer present for the first time with localized non-muscle invasive bladder cancer (NMIBC). It is further estimated that of those newly diagnosed NMIBC cases, 70% present with what the European Association of Urologists classifies as low-risk disease (2).Current recommended clinical practice for the treatment of low-risk NMIBC is cystoscopic transurethral resection of bladder tumor (TURBT) followed by an immediate postoperative intravesical instillation of a chemotherapeutic agent. Without adjuvant treatment, as many as 35.8% of patients treated for low-risk NMIBC will suffer recurrence within 2 years (3). There have been several studies and meta-analyses published indicating that the immediate postoperative instillation of adjuvant therapy may lead to a decrease in the overall risk of recurrence of up to 39%, with absolute reduction in recurrence rates as high as 17% (4). While clearly effective in reducing recurrence, several recently conducted surveys have revealed that immediate single-dose post-operative adjuvant therapy is not consistently administered (5, 6). A prominently cited reason among those clinicians who do not administer immediate post-operative chemotherapy is that the potential for systemic exposure and agent-associated toxicity outweighs the clinical benefit, especially in cases where bladder perforation is suspected. The perceived clinical benefit-torisk ratio argument seems justified given that while patients with low-and intermediate-risk NMIBC have a high rate of recurrence, the initial risk of progression is low (0.8% and 6% at 5 years, respectively) (2). However, the risk of progression increases with the number and interval of recurrences, so any initial prevention or delay of recurrence would be of clear benefit (2). Moreover, because of the high rate of recurrence, frequent monitoring and treatment are required, making NMIBC one of the most expensive cancer types to treat over the course of the disease (7). Therefore, an effective agent for use in the immediate post-operative setting would impart considerable pharmacoeconomic benefit. Recent failures in mid-and late-stage clinical trials highlight the unmet clinical need for the development of new agents that can be safely administered in the immediate post-operative setting (8).

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Section: Discussionsupporting

confidence: 83%

Section: Been Previously Characterized As An Integrin-specific Oncolymentioning

confidence: 99%

Section: Been Previously Characterized As An Integrin-specific Oncolymentioning

confidence: 99%

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A Single Intravesical Instillation of VAX014 Inhibits Orthotopic Superficial Bladder Tumor Implantation to Increase Survival

Hancock

McGuire

Tsuji

et al. 2016

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“…EILDV had shown efficacy in inhibiting bladder cell adhesion on a fibronectin monomatrix, while in the natural environment of the murine bladder EILDV alone was ineffective in inhibiting tumour outgrowth [7]. Yamamoto et al .…”

Section: Discussionmentioning

confidence: 99%

“…In the ECM of the bladder wall fibronectin, collagen, and laminin are the main promoters of cell attachment [6]. Previous studies have shown more effective inhibition of tumour cell adhesion by combining integrin receptor‐blocking oligopeptides with different binding specifities as compared with using single oligopeptides [7]. In the present study, our primary goal was to evaluate a novel mixture of oligopeptides for its anti‐adhesive properties.…”

Section: Introductionmentioning

confidence: 99%

Bioluminescence imaging to monitor bladder cancer cell adhesion in vivo: a new approach to optimize a syngeneic, orthotopic, murine bladder cancer model

2007

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OBJECTIVE To improve the orthotopic murine bladder cancer model by using bioluminescent (BL) MB49 tumour cells for noninvasive in vivo monitoring of tumour growth and to examine the efficacy of integrin receptor‐blocking oligopeptides on preventing tumour cell adhesion in this improved bladder cancer model. MATERIALS AND METHODS The capacity of oligopeptide combinations to interfere with tumour cell adhesion was assessed in vivo in a syngeneic, orthotopic, murine bladder cancer model. Tumour outgrowth was monitored noninvasively by bioluminescence imaging (BLI) after administration of luciferase‐expressing MB49LUC bladder cancer cells. The presence of tumour cells was verified histologically and immunohistochemically on paraffin wax‐embedded sections of excised bladders. RESULTS Anti‐adhesive oligopeptides effectively inhibited tumour outgrowth. BLI detected tumour cells at an early stage when there were no clinical signs of cancer in any of the mice. The technique has high sensitivity in detecting tumour cell implantation, but is less reliable in assessing tumour volume in advanced‐stage disease due to light attenuation in large tumours. CONCLUSIONS Peptides targeting adhesion molecules prevent attachment of bladder cancer cells to the injured bladder wall. BLI is a sensitive method for detecting luminescent bladder cancer cells in an orthotopic mouse model.

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Intravesical chemotherapy

Türkeri

Wientjes

2015

Bladder Cancer

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Inhibition of Bladder Carcinoma Cell Adhesion by Oligopeptide Combinations in Vitro and in Vivo

Abstract: Combining oligopeptides with various specificities significantly inhibited tumor cell adhesion and tumor outgrowth. Application of this principle in a clinical setting may be an effective method for reducing the recurrence rate of superficial bladder cancer.

Cited by 27 publications

References 50 publications

A Single Intravesical Instillation of VAX014 Inhibits Orthotopic Superficial Bladder Tumor Implantation to Increase Survival

A Single Intravesical Instillation of VAX014 Inhibits Orthotopic Superficial Bladder Tumor Implantation to Increase Survival

Bioluminescence imaging to monitor bladder cancer cell adhesion in vivo: a new approach to optimize a syngeneic, orthotopic, murine bladder cancer model

Intravesical chemotherapy

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