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Nature Communications Jun 2024Accurate identification of genetic alterations in tumors, such as Fibroblast Growth Factor Receptor, is crucial for treating with targeted therapies; however, molecular...
Accurate identification of genetic alterations in tumors, such as Fibroblast Growth Factor Receptor, is crucial for treating with targeted therapies; however, molecular testing can delay patient care due to the time and tissue required. Successful development, validation, and deployment of an AI-based, biomarker-detection algorithm could reduce screening cost and accelerate patient recruitment. Here, we develop a deep-learning algorithm using >3000 H&E-stained whole slide images from patients with advanced urothelial cancers, optimized for high sensitivity to avoid ruling out trial-eligible patients. The algorithm is validated on a dataset of 350 patients, achieving an area under the curve of 0.75, specificity of 31.8% at 88.7% sensitivity, and projected 28.7% reduction in molecular testing. We successfully deploy the system in a non-interventional study comprising 89 global study clinical sites and demonstrate its potential to prioritize/deprioritize molecular testing resources and provide substantial cost savings in the drug development and clinical settings.
Topics: Humans; Deep Learning; Algorithms; Biomarkers, Tumor; Clinical Trials as Topic; Urinary Bladder Neoplasms; Male; Female; Patient Selection; Urologic Neoplasms
PubMed: 38824132
DOI: 10.1038/s41467-024-49153-9 -
Clinics in Laboratory Medicine Jun 2024Urothelial carcinoma is characterized by the presence of a wide spectrum of histopathologic features and molecular alterations that contribute to its morphologic and... (Review)
Review
Urothelial carcinoma is characterized by the presence of a wide spectrum of histopathologic features and molecular alterations that contribute to its morphologic and genomic heterogeneity. It typically harbors high rates of somatic mutations with considerable genomic and transcriptional complexity and heterogeneity that is reflective of its varied histomorphologic and clinical features. This review provides an update on the recent advances in the molecular characterization and novel molecular taxonomy of urothelial carcinoma and variant histologies.
Topics: Humans; Carcinoma, Transitional Cell; Pathology, Molecular; Urologic Neoplasms; Urinary Bladder Neoplasms; Urothelium; Mutation
PubMed: 38821640
DOI: 10.1016/j.cll.2023.08.010 -
Cancer Medicine Jun 2024En-Bloc transurethral resection of bladder tumor (ERBT) was clinically used to resect non-muscle-invasive bladder cancer (NMIBC). However, discrepancies persist... (Meta-Analysis)
Meta-Analysis Review Comparative Study
BACKGROUND
En-Bloc transurethral resection of bladder tumor (ERBT) was clinically used to resect non-muscle-invasive bladder cancer (NMIBC). However, discrepancies persist regarding the comparisons between ERBT and conventional transurethral resection of bladder tumor (cTURBT).
METHODS
We conducted a comprehensive search in PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and performed manual searches of reference lists to collect and extract data. Data evaluation was carried out using Review Manager 5.4.0, Rx64 4.1.3, and relevant packages.
RESULTS
There were nine eligible meta-analyses and nine eligible RCTs in our study. NMIBC patients undergoing ERBT were significant associated with a lower rate of bladder perforation and obturator nerve reflex compared to those receiving cTURBT. Our pooled result indicated that ERBT and cTURBT required similar operation time. Regarding postoperative outcomes, ERBT demonstrated superior performance compared to cTURBT in terms of detrusor muscle presence, catheterization time, and residual tumor. ERBT exhibited a higher rate of three-month recurrence-free survival (RFS) compared to those receiving cTURBT (p < 0.05; I = 0%). In bipolar subgroup, ERBT had a significant better 12-month RFS than cTURBT (p < 0.05; I = 0%). Simultaneously, the exclusion of Hybrid Knife data revealed a significant improvement in 12-month RFS associated with ERBT (p < 0.05; I = 50%).
CONCLUSION
Using a combination of umbrella review and meta-analysis, we demonstrated that ERBT had better or comparable perioperative outcome and improved 3 and 12 month RFS than cTURBT. We suggest that ERBT maybe a better surgical method for patients with NMIBC compared with cTURBT.
Topics: Humans; Urinary Bladder Neoplasms; Cystectomy; Treatment Outcome; Urethra; Neoplasm Invasiveness; Non-Muscle Invasive Bladder Neoplasms
PubMed: 38819629
DOI: 10.1002/cam4.7323 -
Supportive Care in Cancer : Official... May 2024This study aimed to develop a patient-centered survivorship care plan (SCP) for US military Veteran bladder cancer (BC) survivors in accordance with the National Academy...
PURPOSE
This study aimed to develop a patient-centered survivorship care plan (SCP) for US military Veteran bladder cancer (BC) survivors in accordance with the National Academy of Medicine recommendation that survivors receive an SCP at treatment completion. BC, which differentially impacts older men, is a costly and highly recurrent cancer associated with invasive procedures and long-term surveillance. Veteran BC survivors may face challenges navigating the patient-to-survivor transition due to their age and comorbidities.
METHODS
We conducted 20 one-on-one qualitative interviews and 2 focus groups with Veteran BC survivors to understand their preferences for information and support to inform SCP development. Data were analyzed using rapid analysis.
RESULTS
Participants voiced concerns about BC's impact on their psychosocial functioning and quality of life. They suggested information on BC recurrences, recommended surveillance schedules, long-term side effects and healthy living, and how and when to seek help if a medical problem arises should be included on the SCP to help manage expectations and access key resources during survivorship. Although participants had varying needs, many recommended including information on supportive resources (e.g., support groups, peer support programs) to manage cancer-related anxiety. Participants also suggested including Veteran-centered information (e.g., Veterans' BC risk factors).
CONCLUSION
We developed an SCP to help Veteran BC survivors navigate the transition from patient to survivor. Adapting an SCP to address specific needs of the Veteran population was an important step in supporting Veteran BC survivors. Future research should evaluate the potential effectiveness of this SCP at improving Veterans' health outcomes and healthcare experiences.
Topics: Humans; Urinary Bladder Neoplasms; Male; Aged; Cancer Survivors; Middle Aged; Patient-Centered Care; Focus Groups; Veterans; Survivorship; Qualitative Research; Patient Care Planning; Female; Quality of Life; Aged, 80 and over; Interviews as Topic; United States
PubMed: 38819504
DOI: 10.1007/s00520-024-08588-y -
Pathologie (Heidelberg, Germany) May 2024Urothelial carcinoma (UC) is by far the most common malignant neoplasm of the urinary bladder; however, there are both benign and malignant changes of the urothelium... (Review)
Review
Urothelial carcinoma (UC) is by far the most common malignant neoplasm of the urinary bladder; however, there are both benign and malignant changes of the urothelium which morphologically resemble urothelial carcinomas or other carcinomas of the urinary bladder. Thus, these mimickers can cause problems in the histomorphological diagnosis. This article provides an overview of possible mimickers and pitfalls of bladder cancer as well as practical notes on the diagnostic procedure, partly using case studies.
PubMed: 38816588
DOI: 10.1007/s00292-024-01335-4 -
Cellular and Molecular Biology... May 2024Bladder tumors occur more frequently in men than in women and are the fourth most common malignancy after prostate, lung, and colon cancers. In this study, we examined...
Bladder tumors occur more frequently in men than in women and are the fourth most common malignancy after prostate, lung, and colon cancers. In this study, we examined the expression of chlorine ion channel 1 and chlorine ion channel 3 in localized bladder tumors according to their stage. We conducted a retrospective analysis of a prospective cohort study spanning from May 2018 to January 2020. This study involved a group of 55 patients who had been diagnosed with primary bladder cancer and underwent transurethral resection of bladder tumor under either general or spinal anesthesia. In addition, 30 patients who underwent cystoscopy due to etiology of hematuria and biopsies were taken from suspicious areas and whose results were normal were included as the control group. The collected samples were evaluated using real-time polymerase chain reaction in a medical genetics laboratory. In our study, it was observed that chlorine ion channel 3 gene expression increased significantly (P<0.001) in all cancer tissues compared to the control group, whereas no significant increase was found in chlorine ion channel 1 gene expression compared to the control group. The data obtained, especially for chlorine ion channel 3, are promising in terms of their use in the treatment of bladder tumors in humans.
Topics: Humans; Urinary Bladder Neoplasms; Female; Male; Middle Aged; Chloride Channels; Aged; Gene Expression Regulation, Neoplastic; Retrospective Studies; Prospective Studies
PubMed: 38814232
DOI: 10.14715/cmb/2024.70.5.11 -
Cellular and Molecular Biology... May 2024In recent years, bladder carcinoma (BC) has shown an increasing incidence, with poor patient outcomes. In clinical practice, BC is still mainly treated by surgery...
In recent years, bladder carcinoma (BC) has shown an increasing incidence, with poor patient outcomes. In clinical practice, BC is still mainly treated by surgery combined with chemoradiotherapy. However, as chemotherapy resistance of tumor cells becomes more and more obvious, it is urgent to find more effective BC treatment regimes. With the increasing application and growing attention paid to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in various neoplastic diseases, EGFR-TKIs have been considered as a new treatment direction in the future. In this study, the research team used AG1478, an EGFR-TKI, to intervene with the BC cell line T24. It was found that the cell activity was statistically decreased, the apoptosis was enhanced, and the cells were dominantly arrested in the G0/G1 phase, confirming the future therapeutic potential of EGFR-TKIs in BC. Besides, the research team further observed that AG1478 also promoted pyroptosis in T24 cells, and its mechanism is related to the induction of mitochondrial oxidative stress damage. The findings lay a more reliable foundation for the future application of EGFR-TKIs in BC.
Topics: Humans; ErbB Receptors; Urinary Bladder Neoplasms; Mitochondria; Apoptosis; Cell Line, Tumor; Tyrphostins; Protein Kinase Inhibitors; Quinazolines; Cell Cycle Checkpoints; Oxidative Stress; Pyroptosis; Cell Proliferation
PubMed: 38814206
DOI: 10.14715/cmb/2024.70.5.38 -
Frontiers in Immunology 2024Bladder cancer is a common type of cancer around the world, and the majority of patients are diagnosed with non-muscle-invasive bladder cancer (NMIBC). Although low-risk...
Bladder cancer is a common type of cancer around the world, and the majority of patients are diagnosed with non-muscle-invasive bladder cancer (NMIBC). Although low-risk NMIBC has a good prognosis, the disease recurrence rate and development of treatment-refractory disease remain high in intermediate- to high-risk NMIBC patients. To address these challenges for the treatment of NMIBC, a novel combination therapy composed of an oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), and relaxin (RLX; HY-oAd) and a clinical-stage glycogen synthase kinase (GSK)-3β inhibitor (9-ING-41; elraglusib) was investigated in the present report. Our findings demonstrate that HY-oAd and 9-ING-41 combination therapy (HY-oAd+9-ING-41) exerted superior inhibition of tumor growth compared with respective monotherapy in a syngeneic NMIBC tumor model. HY-oAd+9-ING-41 induced high-level tumor extracellular matrix (ECM) degradation and a more potent antitumor immune response than the respective monotherapy. In detail, HY-oAd+9-ING-41 induced superior accumulation of intratumoral T cells, prevention of immune cell exhaustion, and induction of tumor-specific adaptive immune response compared to either monotherapy. Collectively, these results demonstrate that the combination of HY-oAd and 9-ING-41 may be a promising approach to elicit a potent antitumor immune response against bladder cancer.
Topics: Urinary Bladder Neoplasms; Tumor Microenvironment; Animals; Adenoviridae; Oncolytic Virotherapy; Oncolytic Viruses; Mice; Humans; Glycogen Synthase Kinase 3 beta; Cell Line, Tumor; Combined Modality Therapy; Female
PubMed: 38812516
DOI: 10.3389/fimmu.2024.1360436 -
European Journal of Medical Research May 2024The basic helix-loop-helix family member e41 (BHLHE41) is frequently dysregulated in tumors and plays a crucial role in malignant progression of various cancers....
BACKGROUND
The basic helix-loop-helix family member e41 (BHLHE41) is frequently dysregulated in tumors and plays a crucial role in malignant progression of various cancers. Nevertheless, its specific function and underlying mechanism in bladder cancer (BCa) remain largely unexplored.
METHODS
The expression levels of BHLHE41 in BCa tissues and cells were examined by qRT-PCR and western blot assays. BCa cells stably knocking down or overexpressing BHLHE41 were constructed through lentivirus infection. The changes of cell proliferation, cell cycle distribution, migration, and invasion were detected by CCK-8, flow cytometry, wound healing, transwell invasion assays, respectively. The expression levels of related proteins were detected by western blot assay. The interaction between BHLHE41 and PYCR1 was explored by co-immunoprecipitation analysis.
RESULTS
In this study, we found that BHLHE41 was lowly expressed in bladder cancer tissues and cell lines, and lower expression of BHLHE41 was associated with poor overall survival in bladder cancer patients. Functionally, by manipulating the expression of BHLHE41, we demonstrated that overexpression of BHLHE41 significantly retarded cell proliferation, migration, invasion, and induced cell cycle arrest in bladder cancer through various in vitro and in vivo experiments, while silence of BHLHE41 caused the opposite effect. Mechanistically, we showed that BHLHE41 directly interacted with PYCR1, decreased its stability and resulted in the ubiquitination and degradation of PYCR1, thus inactivating PI3K/AKT signaling pathway. Rescue experiments showed that the effects induced by BHLHE41 overexpression could be attenuated by further upregulating PYCR1.
CONCLUSION
BHLHE41 might be a useful prognostic biomarker and a tumor suppressor in bladder cancer. The BHLHE41/PYCR1/PI3K/AKT axis might be a potential therapeutic target for bladder cancer intervention.
Topics: Urinary Bladder Neoplasms; Humans; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Pyrroline Carboxylate Reductases; Cell Proliferation; delta-1-Pyrroline-5-Carboxylate Reductase; Basic Helix-Loop-Helix Transcription Factors; Cell Movement; Disease Progression; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Mice; Animals; Male
PubMed: 38811952
DOI: 10.1186/s40001-024-01889-2 -
Journal of Medical Case Reports May 2024Although 5-aminolevulinic acid is useful for the photodynamic diagnosis of bladder tumors, it often causes severe intraoperative hypotension. We report a case of...
BACKGROUND
Although 5-aminolevulinic acid is useful for the photodynamic diagnosis of bladder tumors, it often causes severe intraoperative hypotension. We report a case of postoperative cardiac arrest in addition to severe intraoperative hypotension, probably owing to the use of 5-aminolevulinic acid.
CASE PRESENTATION
An 81-year-old Japanese man was scheduled to undergo transurethral resection of bladder tumor. The patient took 5-aminolevulinic acid orally 2 hours before entering the operating room. After the induction of anesthesia, his blood pressure decreased to 47/33 mmHg. The patient's hypotension did not improve even after noradrenaline was administered. After awakening from anesthesia, the patient's systolic blood pressure increased to approximately 100 mmHg, but approximately 5 hours after returning to the ward, cardiac arrest occurred for approximately 12 seconds.
CONCLUSION
We experienced a case of postoperative cardiac arrest in a patient, probably owing to the use of 5-aminolevulinic acid. Although the cause of cardiac arrest is unknown, perioperative hemodynamic management must be carefully performed in patients taking 5-aminolevulinic acid.
Topics: Humans; Male; Aminolevulinic Acid; Hypotension; Aged, 80 and over; Heart Arrest; Urinary Bladder Neoplasms; Postoperative Complications; Photosensitizing Agents; Intraoperative Complications
PubMed: 38811941
DOI: 10.1186/s13256-024-04589-x