Project description:Purpose: While molecular targeted therapy has revolutionized the treatment of many cancers, little progress has been made in the development of novel therapies for muscle invasive bladder cancer (MIBC). Here we report on the establishment and characterization of patient-derived primary MIBC xenografts Tumor fragments derived from 7 patients with MIBC were grafted under the renal capsule of NOD-SCID mice and subsequently transplanted to further mice over multiple generations. Patient tumor and xenograft tissue were processed for analysis of , gene expression by microarray, and expression of select potential target pathways by immunohistochemistry (IHC).
Project description:Purpose: While molecular targeted therapy has revolutionized the treatment of many cancers, little progress has been made in the development of novel therapies for muscle invasive bladder cancer (MIBC). Here we report on the establishment and characterization of patient-derived primary MIBC xenografts
2015-03-27 | GSE67312 | GEO
Project description:Case report: Novel genetic variant associated with epilepsy
| PRJNA956710 | ENA
Project description:A case of pneumonia caused by infection with Tropheryma whipplei complicated by cryptococcus during treatment with a Janus kinase inhibitor: A case report
Project description:The goals of this study are to screen differential expression profiles of tRNA-Derived small RNAs (tsRNAs) in muscle-invasive bladder cancer (MIBC) in Chinese population using next-generation sequencing and qRT-PCR.As a result, in MIBC tissues, 406 tsRNAs were differentially expressed between in MIBC tissues. Of them, 91 tsRNAs were significantly differentially expressed (fold change>1.5; P<0.05): 65 tsRNAs were significantly up-regulated whereas 26 were significantly down-regulated in MIBC.Taken together,this study explored, for the first time, the significant alteration of tsRNA expression profiles in MIBC in Chinese population and offered deep insights into many possible treatment targets of MIBC by regulating tsRNAs.
Project description:Urothelial carcinoma (UC) of the urinary bladder has significant challenges in treatment due to its diverse genetic landscape and variable response to systemic therapy. In recent years, patient-derived organoids (PDOs) emerged as a novel tool to model primary tumors with higher resemblance than conventional 2D cell culture approaches. However, the potential of organoids to predict therapy response in a clinical setting remains to be evaluated. This study explores the clinical feasibility of PDOs for pharmacotyping in UC. Initially, we subjected tumor tissue specimens from 50 patients undergoing transurethral resection or radical cystectomy to organoid propagation, of whom 19 (38%) yielded PDOs suitable for drug sensitivity assessment. Notably, whole transcriptome-based analysis indicated that PDOs may show phenotypes distinct from their parental tumor tissue. Pharmacotyping within a clinically relevant timeframe [mean of 35.44 and 55 days for non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), respectively] was achieved. Drug sensitivity analyses revealed marked differences between NMIBC and MIBC, with MIBC-derived organoids demonstrating higher chemosensitivity toward clinically relevant drugs. A case study correlating organoid response with patient treatment outcome illustrated the complexity of predicting chemotherapy efficacy, especially considering the rapid acquisition of drug resistance. We propose a workflow of prospective organoid-based pharmacotyping in UC, enabling further translational research and integration of this approach into clinical practice.
2024-11-03 | GSE280749 | GEO
Project description:Case Report: Chlamydia psittaci Pneumonia Complicated by Guillain-Barre Syndrome Detected Using Metagenomic Next-Generation Sequencing
Project description:Muscle-invasive bladder cancer (MIBC) is an aggressive disease with high morbidity and mortality that can be divided into basal and luminal subtypes based on genomic characteristics. Due to the complex heterogeneity of MIBC, specific markers are needed to distinguish MIBC subtypes to guide future clinical treatment. In this study, we explore abnormal lncrnas that are specific to the basic and intracavitary subtypes of MIBC, which will provide potential biomarkers for precision therapy of MIBC.
Project description:Muscle invasive bladder cancer (MIBC) is a heterogeneous disease with a high recurrence rate and poor clinical outcomes. Molecular subtype provides a new framework for the study of MIBC heterogeneity. Clinically, MIBC can be classified as basal and luminal subtypes, they display different clinical and pathological characteristics, but the molecular mechanism is still unclear. Lipidomic and metabolomic molecules have recently been considered to play an important role in the genesis and development of tumors, especially as potential biomarkers. Their different expression profiles in basal and luminal subtypes provide clues for the molecular mechanism of basal and luminal subtypes and the discovery of new biomarkers. Herein, we stratified MIBC patients into basal and luminal subtype using a MIBC classifier based on transcriptome expression profiles. We qualitatively and quantitatively analyzed the lipids and metabolites of basal and luminal MIBC subtypes, and identified differential lipid and metabolite profiles of them. Our results suggest that free fatty acids (FFA) and sulfatides (SL), which are closely associated with immune and stromal cell types, can contribute to the diagnosis of basal and luminal subtypes of MIBC. Moreover, we showe that glycerophosphocholine (GCP)/imidazoles and nucleosides/imidazoles ratios can accurately distinguish the basal and luminal tumors. Overall, by integrating transcriptomic, lipidomic, and metabolomic data, our study reveals specific biomarkers to differentially diagnose basal and luminal MIBC subtypes and may provide a basis for precision therapy of MIBC.
Project description:Novel treatment modalities are imperative for the challenging management of muscle-invasive and metastatic BC to improve patient survival rates. The recently identified lysine methyltransferase (KMT) 9, an obligate heterodimer composed of KMT9α and KMT9β, regulates the growth of various types of tumors such as prostate, lung and colon cancer. While overexpression of KMT9α was previously observed to be associated with aggressive basal-like MIBC in an analysis of patients’ tissue samples, a potential functional role of KMT9 in this type of cancer has not been investigated to date. In this study, we show that KMT9 regulates proliferation and migration of various MIBC cell lines with different genetic mutations. KMT9α depletion results in differential expression of genes involved in the regulation of the cell cycle, cell adhesion and migration. Reduced cell proliferation upon KMT9α depletion is also observed in Pten/Trp53 knockout bladder tumor organoids, which cannot be rescued with an enzymatically inactive KMT9α mutant. In accordance with the idea that the catalytic activity of KMT9 is required for the control of cellular processes in MIBC, a recently developed small molecule inhibitor of KMT9 (KMI169) also impairs cancer cell proliferation. Since KMT9α depletion also restricts the growth of xenografts in mice, our data suggest that KMT9 is an actionable novel therapeutic target for the treatment of MIBC.