Early-stage bladder cancer occurs as two distinct forms: namely, low-grade superficial disease and high-grade carcinoma in situ (CIS), which is the major precursor of muscle-invasive bladder cancer. Although the low-grade form is readily treatable, few, if any, effective treatments are currently available for preventing progression of nonmuscle-invasive CIS to invasive bladder cancer. Based on our previous findings that the mammalian target of Rapamycin (mTOR) signaling pathway is activated in muscle-invasive bladder cancer, but not superficial disease, we reasoned that suppression of this pathway might block cancer progression. To test this idea, we performed in vivo preclinical studies using a genetically engineered mouse model that we now show recapitulates progression from nonmuscle-invasive CIS to muscle-invasive bladder tumors. We find that delivery of Rapamycin, an mTOR inhibitor, subsequent to the occurrence of CIS effectively prevents progression to invasive bladder cancer. Furthermore, we show that intravesical delivery of Rapamycin directly into the bladder lumen is highly effective for suppressing bladder tumorigenesis. Thus, our findings show the potential therapeutic benefit of inhibiting mTOR signaling for treatment of patients at high risk of developing invasive bladder cancer. More broadly, our findings support a more widespread use of intravesical delivery of therapeutic agents for treatment of high-risk bladder cancer patients, and provide a mouse model for effective preclinical testing of potential novel agents.
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http://dx.doi.org/10.1158/1940-6207.CAPR-09-0169 | DOI Listing |
Molecules
January 2025
Department of Toxicology, Poznan University of Medical Sciences, Rokietnicka 3 Street, 60-806 Poznan, Poland.
Although curcumin is a well-known natural polyphenol with many biological activities, its clinical application has been limited by low aqueous solubility and stability. Therefore, curcumin derivatives have been proposed to overcome these limitations and increase anticancer activity. This study tested curcumin derivatives with modified feruloyl moieties ( and ) and the β-diketo moiety () to better understand their anticancer mechanism against human bladder cancer cells.
View Article and Find Full Text PDFMolecules
January 2025
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
The overexpression of the epidermal growth factor receptor (EGFR) in certain types of prostate cancers and glioblastoma makes it a promising target for targeted radioligand therapy. In this context, pairing an EGFR-targeting peptide with the emerging theranostic pair comprising the Auger electron emitter cobalt-58m (Co) and the Positron Emission Tomography-isotope cobalt-55 (Co) would be of great interest for creating novel radiopharmaceuticals for prostate cancer and glioblastoma theranostics. In this study, GE11 (YHWYGYTPQNVI) was investigated for its EGFR-targeting potential when conjugated using click chemistry to N1-((triazol-4-yl)methyl)-N1,N2,N2-tris(pyridin-2-ylmethyl)ethane-1,2-diamine (TZTPEN).
View Article and Find Full Text PDFMedicina (Kaunas)
January 2025
Urology Department, Metropolitan Hospital, Neo Faliro, 18547 Piraeus, Greece.
Despite the high incidence of bladder cancer (it represents the 7th most common cancer in males), EAU guidelines do not recommend any technique for screening and prevention, whereas the main diagnostic tools remain computed tomography urography (CTU), cytology, and cystoscopy. Unfortunately, these gold-standard modalities are mainly characterized by low sensitivity and accuracy. To minimize the limitations and increase the detection rates of urothelial cancer, several technologies have been developed.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Medical Biology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53020, Türkiye.
The innate immune response serves as the primary defense against viral infections, with the recognition of viral nucleic acids by pattern recognition receptors (PRRs) initiating antiviral responses. Mitochondrial antiviral-signaling protein (MAVS) acts as a pivotal adaptor protein in the RIG-I pathway. Alternative splicing further diversifies MAVS isoforms.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Department of Urology and Oncological Urology, MSWiA Hospital, Warmian-Masurian Cancer Center, 10-228 Olsztyn, Poland.
Despite advances in prophylaxis, early diagnosis, and treatment, urogenital cancers represent a significant challenge to public health in Poland due to their relatively high prevalence and mortality rates. This narrative review aims to explore contemporary evidence on the epidemiology of urogenital cancers in Poland, such as prostate cancer, bladder cancer, kidney cancer, testicular cancer, and penile cancer, focusing on current and historical status and trends in the broader context of healthcare delivery. The literature consistently indicates that urogenital cancer continues to be a significant contributor to cancer incidence and mortality rates in Poland.
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