as-1411 and Kidney-Neoplasms

DNA aptamers represent a novel strategy in anti-cancer medicine. AS1411, a DNA aptamer targeting nucleolin (a protein which is overexpressed in many tumor types), was evaluated in patients with metastatic, clear-cell, renal cell carcinoma (RCC) who had failed treatment with ≥1 prior tyrosine kinase inhibitor.. In this phase II, single-arm study, AS1411 was administered at 40 mg/kg/day by continuous intravenous infusion on days 1-4 of a 28-day cycle, for two cycles. Primary endpoint was overall response rate; progression-free survival (PFS) and safety were secondary endpoints.. 35 patients were enrolled and treated. One patient (2.9 %) had a response to treatment. The response was dramatic (84 % reduction in tumor burden by RECIST 1.0 criteria) and durable (patient remains free of progression 2 years after completing therapy). Whole exome sequencing of this patient's tumor revealed missense mutations in the mTOR and FGFR2 genes which is of interest because nucleolin is known to upregulate mTOR pathway activity by enhancing AKT1 mRNA translation. No other responses were seen. Thirty-four percent of patients had an AS1411-related adverse event, all of which were mild or moderate.. AS1411 appears to have minimal activity in unselected patients with metastatic RCC. However, rare, dramatic and durable responses can be observed and toxicity is low. One patient in this study had an excellent response and was found to have FGFR2 and mTOR mutations which will be of interest in future efforts to discover and validate predictive biomarkers of response to nucleolin targeted compounds. DNA aptamers represent a novel way to target cancer cells at a molecular level and continue to be developed with a view to improving treatment and imaging in cancer medicine.

Topics: Adult; Aged; Aged, 80 and over; Aptamers, Nucleotide; Carcinoma, Renal Cell; Demography; Exome; Female; Humans; INDEL Mutation; Infusions, Intravenous; Kidney Neoplasms; Male; Middle Aged; Models, Molecular; Neoplasm Metastasis; Nucleolin; Oligodeoxyribonucleotides; Phosphoproteins; RNA-Binding Proteins; Sequence Analysis, DNA; Treatment Outcome

Early diagnosis of renal cell carcinoma is extremely significant for the effective treatment of kidney cancer. The development of AS1411 aptamer modified Mn-MoS2 QDs provides a promising fluorescence/magnetic resonance (MR) dual-modal imaging probe for the precise diagnosis of renal clear cell carcinoma.. In this work, Mn-MoS. The prepared Mn-MoS. These results demonstrated the potential of AS1411-Mn-MoS

Topics: Animals; Aptamers, Nucleotide; Carcinoma, Renal Cell; Cell Death; Cell Line, Tumor; Disulfides; Female; Fluorescence; Humans; Kidney Neoplasms; Magnetic Resonance Imaging; Manganese; Mice; Molybdenum; Oligodeoxyribonucleotides; Quantum Dots; Staining and Labeling

Magnetic resonance imaging (MRI) with high spatial resolution has been widely used in clinics as a noninvasive diagnostic technology, and MRI diagnosis-based theranostic nanomaterials have attracted increasing attention. Herein, we report on the fabrication of a GO/BSA-Gd2O3/AS1411-DOX theranostic nanocomplex with BSA-Gd2O3 nanoparticles for use as an MRI contrast agent (CA), with graphene oxide (GO) nanoplates as the CA and drug nanocarrier, as well as an aptamer, AS1411, as the targeting molecule. The proposed theranostic nanocomplex not only provided stronger MR contrast enhancement but also inhibited the growth of 786-0 human renal carcinoma cells with the help of the AS1411 aptamer, while sparing the normal cells from harm, thus demonstrating their specific drug delivery capability. Additionally, 786-0 cells could be specifically recognized using the GO/BSA-Gd2O3/AS1411-DOX theranostic nanocomplex with MRI both in vitro and in vivo. Notably, most of the nanocomplex that was injected into the tail vein was excreted by the kidneys and bladder, while MRI signals from the nanocomplexes that accumulated specifically in the tumor region could remain as long as 24 hours, which is beneficial for future clinical diagnosis and therapy.

Topics: Animals; Antineoplastic Agents; Aptamers, Nucleotide; Cell Line, Tumor; Cell Proliferation; Contrast Media; Doxorubicin; Drug Delivery Systems; Gadolinium; Graphite; Humans; Kidney Neoplasms; Magnetic Resonance Imaging; Mice; Mice, Inbred BALB C; Nanoparticles; Oligodeoxyribonucleotides; Theranostic Nanomedicine; Tissue Distribution