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Expression data from mice bladder with MB49-induced cancer treated with alpha1-oleate.

ABSTRACT: Potent chemotherapeutic agents are required to counteract the aggressive behavior of cancer cells and patients often experience severe side effects, due to tissue toxicity. This study addresses if a better balance between efficacy and toxicity can be attained using the tumoricidal complex alpha1-oleate, formed by a synthetic, alpha-helical peptide comprising the N-terminal 39 amino acids of alpha-lactalbumin and the fatty acid oleic acid. Bladder cancer was established, by intra-vesical instillation of MB49 cells on day 0 and the treatment group received five instillations of alpha1-oleate (1.7-17mM) on days 3-11. A dose-dependent reduction in tumor size, bladder size and bladder weight was recorded in the alpha1-oleate treated group, compared to sham-treated mice. Tumor markers Ki-67, Cyclin D1 and VEGF were inhibited in a dose-dependent manner, as was the expression of cancer-related genes. Remarkably, toxicity for healthy tissue was not detected in alpha1-oleate-treated, tumor bearing mice or in healthy mice or rabbits, challenged with increasing doses of the active complex. The results define a dose-dependent therapeutic effect of alpha1-oleate in a murine bladder cancer model.

ORGANISM(S): Mus musculus

PROVIDER: GSE148308 | GEO | 2020/04/09

REPOSITORIES: GEO

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Expression data from mice bladder with MB49-induced cancer treated with alpha1-oleate alone or in combination Epirubicin or Mitomycin C, short-term effects

Project description:Bladder cancer is common and one of the most costly cancer forms, due to a lack of curative therapies. Recently, clinical safety and efficacy of the alpha1-oleate complex was demonstrated in a placebo-controlled study of non-muscle invasive bladder cancer. This study investigated if long-term therapeutic efficacy is improved by repeated treatment cycles and by combining alpha1-oleate with low-dose chemotherapy. Rapidly growing bladder tumors were treated by intravesical instillation of alpha1-oleate, Epirubicin or Mitomycin C alone or in combination. One treatment cycle arrested tumor growth, with a protective effect lasting at least four weeks in mice receiving 8.5 mM of alpha1-oleate alone or 1.7 mM of alpha-oleate combined with Epirubicin or Mitomycin C. Repeated treatment cycles extended protection, defined by a lack of bladder pathology and a virtual absence of bladder cancer-specific gene expression. Synergy with Epirubicin was detected at the lower alpha1-oleate concentration and alpha1-oleate was shown to enhance the uptake and nuclear translocation of Epirubicin, by tumor cells. Effects at the chromatin level affecting cell proliferation were further suggested by reduced BrdU incorporation. In addition, alpha1-oleate triggered DNA fragmentation, defined by the TUNEL assay. The results suggest that bladder cancer development may be prevented long-term in the murine model, by alpha1-oleate alone or in combination with low-dose Epirubicin. In addition, the combination of alpha1-oleate and Epirubicin reduced the size of established tumors. Exploring these potent preventive and therapeutic effects will be of immediate interest in patients with bladder cancer.

2023-02-25 | GSE209882 | GEO

Expression data from mice bladder with MB49-induced cancer treated with alpha1-oleate alone or in combination Epirubicin or Mitomycin C, long-term effects

2023-02-25 | GSE209881 | GEO

Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex

Project description:Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.

2021-04-15 | GSE172112 | GEO

Expression data from mice bladder with MB49-induced cancer treated with alpha1-oleate.

Project description:Expression data from mice bladder with MB49-induced cancer treated with alpha1-oleate.

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Analysis of transcriptional changes in cell lines (in vitro) and tumors (in vivo) after treatment with interferon α gene therapy.

Project description:Three bladder cancer cell lines were treated with recombinant IFNα, LV-Ctrl or LV-IFNα and compared with control (Ctrl) samples by RNAseq. Also, vehicle treated, LV-Ctrl and LV-IFNα treated murine MB49 bladder cancer tumor model was compared by RNAseq

2022-06-05 | GSE205493 | GEO

RNAseq-based bladder cancer subtyping and IPA analysis with the xenografts from C57 BL/6J

Project description:To subtype the Triple gene knockout tumor we generated and assess the similiarities with widely used MB49 cells, TKO cells were injected into bladder wall orthtopically and bladder lumen by catheter intravesically in C57 BL/6J, while MB49 intravesical injection as a control. TKO intravesical tumors, TKO orthotopic tumors and MB49 intravesical tumors were collected and sent for RNA-seq analysis. In results, both intravesical TKO and orthotopic TKO tumors demonstrates transcriptome profiles that closely resembled human basal like muscle invasive bladder cancer using a luminal/basal/neuronal classifier. Principal Component Analysis (PCA) across samples demonstrated that MB49 cells had transcriptome profiles that differed significantly from TKO tumors. Hence, this study suggest that the TKO tumors closely resemble basal like human bladder cancer and MB49 exhibited no expression of urothelial markers.

2022-06-01 | GSE200005 | GEO

Expression data from mice bladder with MB49-induced cancer treated with Lon protease

Project description:Expression data from mice bladder with MB49-induced cancer treated with Lon protease

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RNAseq of murine MB49 cell line - WT and gal-9-KO - in vitro

Project description:A number of studies have reported evidence of positive or negative contributions of galectin-9 (gal-9) to human and experimental malignancies. Some clinical observations and in vitro experiments suggest that cell-associated gal-9 has anti-metastatic effects. On the other hand, extra-cellular gal-9 consistently enhances tumor immune escape. The aim of this experiment is to study the impact of gal-9 gene invalidation in the murine bladder carcinoma cell line MB49, in vitro. It complements the results of a comparative experiment carried out using the same cells as part of a serial transplantations protocol, whose results are already available on Annotare (E-MTAB-9220).

2020-09-20 | E-MTAB-9570 | biostudies-arrayexpress

Exome-Seq of murine MB49 cell line - WT and gal-9-KO - in vitro

Project description:A number of studies have reported evidence of positive or negative contributions of galectin-9 (gal-9) to human and experimental malignancies. Some clinical observations and in vitro experiments suggest that cell-associated gal-9 has anti-metastatic effects. On the other hand, extra-cellular gal-9 consistently enhances tumor immune escape. The aim of this experiment is to study the impact of gal-9 gene invalidation in the murine bladder carcinoma cell line MB49, in vitro. It complements the results of : 1) a RNAseq analysis performed on in vitro cell cultures ; 2) a comparative experiment carried out using the same cells as part of a serial transplantations protocol, whose results are already available on Annotare (E-MTAB-9570 ; E-MTAB-9220).

2021-01-01 | E-MTAB-9836 | biostudies-arrayexpress

RNAseq of MB49 inoculated tumor-assotiated macrophages from MC-proficient and MC-deficient animals

Project description:RNA seq was used to compare the expression profile of macrophages in presence and absense of mast cells. MB49 cells were injected i.d. into Mcpt5-Cre+ R26DTA animals and cre-negative littermates. Macrophages were sorted at 20 d.p.i.

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