Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1119936 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29273354_1.fastq.gz | Fastqsanger.gz | |||
| SRR29273354_2.fastq.gz | Fastqsanger.gz | |||
| SRR29273355_1.fastq.gz | Fastqsanger.gz | |||
| SRR29273355_2.fastq.gz | Fastqsanger.gz | |||
| SRR29273356_1.fastq.gz | Fastqsanger.gz |
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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
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 | GSE209881 | GEO
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
Project description: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.
2020-04-09 | GSE148308 | GEO
Project description:Expression data from mice bladder with MB49-induced cancer treated with alpha1-oleate.
| PRJNA623875 | ENA
Project description:Although the intravesical instillation of Bacillus Calmette-Guerin (BCG) is widely used as adjuvant treatment for nonmuscle-invasive bladder cancers, the clinical benefit is variable across patients, and the molecular mechanisms underlying the sensitivity to BCG administration and disease progression are poorly understood. To establish the molecular signatures that predict the responsiveness and disease progression of bladder cancers treated with BCG, we performed transcriptome sequencing (RNA-seq) for 13 treatment-naïve and 22 post-treatment specimens obtained from 14 bladder cancer patients. To overcome disease heterogeneity, we used non-negative matrix factorization to identify the latent molecular features associated with drug responsiveness and disease progression. At least 12 molecular features were present, among which the immune-related feature was associated with drug responsiveness, indicating that pre-treatment anti-cancer immunity might dictate BCG responsiveness. We also identified disease progression-associated molecular features indicative of elevated cellular proliferation in post-treatment specimens. The progression-associated molecular features were validated in an extended cohort of BCG-treated bladder cancers. Our study advances understanding of the molecular mechanisms of BCG activity in bladder cancers and provides clinically relevant gene markers for evaluating and monitoring patients.
2023-12-25 | GSE244895 | GEO
Project description:Previous studies successfully revealed molecular characteristics of bladder cancers, dealing with non-muscle invasive bladder cancer and muscle invasive bladder cancer, separately. At the molecular level, however, there is a great need to aggregate these subtypes, which may share biological characteristics. This study aimed to identify distinct molecular subtypes of BC and the clinical and/or biological characteristics of each subtype. We used seven gene expression data sets for bladder cancer, which included data from 118 primary bladder cancer samples and 27 recurrent bladder tumor tissues from the Yonsei University Severance Hospital. Hierarchical clustering revealed four molecular subtypes of BC with different clinical outcomes: class 1 with low-grade NMIBC and the best prognosis; class 2 characterized by active FGFR3 and inhibited immune response pathways; class 3 with high-grade NMIBC and the worst progression-free survival; and class 4 mainly comprised of MIBC along with EMT activation. By applying the classifier based on these characteristics, we stratified all BC samples into newly identified molecular subtypes. When comparing previously reported subtypes, our subtypes well agreed with their molecular characteristics regardless of breast cancer-based biology, and showed a strong prognostic relevance in class 3. Integrative analysis of mutation and gene expression suggested that class 3 may have the potential benefit from anti-PD-L1 immunotherapy. Our classifier, constructed by NMIBC and MIBC integration, successfully stratified BC patients into distinct subtypes with different clinical outcomes and a possible treatment option.
2018-10-03 | GSE120736 | GEO
Project description:Urothelial carcinoma of the bladder is characterized by significant variability in clinical outcomes depending on stage and grade. The addition of molecular information may improve our understanding of such heterogeneity and enhance prognostic prediction. The purpose of this study was to validate and improve published prognostic signatures for high-risk bladder cancer. We evaluated microarray data from 93 bladder cancer patients managed by radical cystectomy to determine gene expression patterns associated with clinical and prognostic variables.
2012-01-23 | E-GEOD-31684 | biostudies-arrayexpress
Project description:Background Clinically useful molecular markers predicting the clinical course of patients diagnosed with non-muscle invasive bladder cancer are needed to improve treatment outcome. Methods We used custom designed oligonucleotide microarrays to validate four previously reported gene expression signatures for molecular diagnosis of disease stage and carcinoma in situ, and for predicting disease recurrence and progression. We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain and France. Molecular classifications were compared to pathological diagnosis and clinical outcome. The median follow-up time for the patients was 3.5 years. Results Classification of disease stage using a 52-gene classifier was found to be highly significantly correlated with pathological stage (P<0.001). Furthermore, the classifier added information regarding future disease progression of Ta or T1 tumors (P<0.001). The molecular 77-gene progression classifier was highly significantly correlated with progression free survival (P<0.001) and cancer specific survival (P=0.001). Furthermore, multivariate Cox´s regression analysis showed the progression classifier to be an independently significant variable associated with disease progression after adjustment for age, sex, stage, grade and treatment (hazard ratio 2.4, P=0.005). The diagnosis of carcinoma in situ (CIS) using a 68-gene classifier showed a highly significant correlation with histopathological CIS diagnosis (odds ratio 5.8, P<0.001) in multivariate logistic regression analysis. Conclusions We conclude that this multicenter validation study confirms the clinical utility of molecular classifiers to guide treatment decisions for patients initially diagnosed with non-muscle invasive bladder cancer. Keywords: Multi center validation study of gene expression signatures
2007-06-15 | GSE5479 | GEO
Project description:Improved risk stratification and predictive biomarkers of treatment response are needed for non–muscle-invasive bladder cancer (NMIBC). Here we assessed the clinical utility of targeted RNA and DNA molecular profiling in NMIBC. We performed RNA-based profiling by NanoString nCounter on non–muscle-invasive bladder cancer (NMIBC) clinical specimens and found that a novel expression signature of an inflamed tumor microenvironment (TME), but not molecular subtyping, was associated with improved recurrence-free survival after bacillus Calmette-Guérin (BCG) immunotherapy. We further demonstrated that immune checkpoint gene expression was not associated with higher recurrence rates after BCG.
2021-10-05 | GSE185264 | GEO