Glutathione-S-Transferase Theta 2 (GSTT2) Modulates the Response to Bacillus Calmette-Guérin Immunotherapy in Bladder Cancer Patients.

Glutathione-S-transferases (GST) enzymes detoxify xenobiotics and are implicated in response to anticancer therapy. This study evaluated the association of GST theta 1 (GSTT1), GSTT2, and GSTT2B with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) response in non-muscle-invasive bladder cancer treatment. In vitro assessments of GSTT2 knockout (KO) effects were performed using cell lines and dendritic cells (DCs) from GSTT2KO mice.

IL-12 minicircle delivery via extracellular vesicles as immunotherapy for bladder cancer.

Interleukin-12 (IL-12) holds significant potential in cancer therapy; however, its clinical applicability is hindered by dose-limiting toxicity. Delivery of the IL-12 gene directly to tumours for constitutive IL-12 expression is a possible strategy to enhance its effectiveness while minimizing systemic toxicity. In this study, we investigate the potential of red blood cell-derived extracellular vesicles (RBCEVs) as a carrier for Il-12 plasmid delivery.

The Bladder Tumor Microenvironment Components That Modulate the Tumor and Impact Therapy.

The tumor microenvironment (TME) is complex and involves many different cell types that seemingly work together in helping cancer cells evade immune monitoring and survive therapy. The advent of single-cell sequencing has greatly increased our knowledge of the cell types present in the tumor microenvironment and their role in the developing cancer. This, coupled with clinical data showing that cancer development and the response to therapy may be influenced by drugs that indirectly influence the tumor environment, highlights the need to better understand how the cells present in the TME work together.

Tumor-targeting albumin nanoparticles as an efficacious drug delivery system and potential diagnostic tool in non-muscle-invasive bladder cancer therapy.

Current intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) has limited efficacy due to loss of the instilled agent from urine voiding and the agent's lack of specificity for the tumors. We developed a nanocarrier (txCD47-HNP, ∼100 nm) based on human serum albumin conjugated with a peptide that targets the cluster of differentiation 47 receptor overexpressed on bladder cancer (BC) cells. The IC of gemcitabine elaidate (GEM) loaded in the txCD47-HNP was almost an order of magnitude lower than that of free GEM.

Predictive biomarkers of response to bacillus Calmette-Guérin immunotherapy and bacillus Calmette-Guérin failure for non-muscle invasive bladder cancer.

Within the heterogeneous population of patients with bacillus Calmette-Guérin failure, there are clear differences in prognosis and therapy with regard to the timeline when bacillus Calmette-Guérin failure occurred. There are a variety of classifications which include bacillus Calmette-Guérin refractory disease, relapsing, unresponsive, and intolerant. Further profiling of these patients may help to shed light on other forms of therapy that are less radical.

Wirelessly Activated Nanotherapeutics for In Vivo Programmable Photodynamic-Chemotherapy of Orthotopic Bladder Cancer.

Photochemical internalization (PCI) is a promising intervention using photodynamic therapy (PDT) to enhance the activity of chemotherapeutic drugs. However, current bladder cancer treatments involve high-dose chemotherapy and high-irradiance PDT which cause debilitating side effects. Moreover, low penetration of light and drugs in target tissues and cumbersome light delivery procedures hinder the clinical utility of PDT and chemotherapy combination for PCI.

Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model.

This study evaluates a short therapy schedule for bladder cancer using BCG Tokyo. BCG Tokyo was evaluated in vitro using bone marrow derived dendritic cells, neutrophils, RAW macrophages and the murine bladder cancer cell line, MB49PSA, and compared to other BCG strains. BCG Tokyo > BCG TICE at inducing cytokine production.

Mindfulness Awareness Practice (MAP) to Prevent Dementia in Older Adults with Mild Cognitive Impairment: Protocol of a Randomized Controlled Trial and Implementation Outcomes.

Background: With an aging population, developing non-pharmacological interventions (NPIs) to delay dementia has become critical. Apart from cognitive decline, dementia is associated with multiple pathophysiology, including increased oxidative stress, dysregulated gene expressions, cytokine, neurotrophin, and stress markers, telomere shortening, and deteriorations in brain connectivity. Although mindfulness practices have been proposed to ameliorate these biological changes, no empirical studies were conducted.

Controllable Assembly of Upconversion Nanoparticles Enhanced Tumor Cell Penetration and Killing Efficiency.

The use of upconversion nanoparticles (UCNPs) for treating deep-seated cancers and large tumors has recently been gaining momentum. Conventional approaches for loading photosensitizers (PS) to UCNPs using noncovalent physical adsorption and covalent conjugation had been previously described. However, these methods are time-consuming and require extra modification steps.

Mental awareness improved mild cognitive impairment and modulated gut microbiome.

There is ample scientific and clinical evidence of the effects of gut microbiota on the brain but no definitive evidence that the brain can affect changes in gut microbiota under the bi-directional gut-brain axis concept. As there is no pharmacotherapeutic intervention for the early stages of cognitive decline, research has focused on cognitive stimulation in reversing or slowing the impairment. Elderly patients diagnosed with mild cognitive impairment underwent a randomized-control trial of mindful awareness practice.

Polymorphism in autophagy gene ATG2B is not associated with bladder cancer recurrence after intravesical Bacillus Calmette-Guerin (BCG) immunotherapy in Asian patients.

Objectives: Optimal patient stratification is critical in the era of personalized medicine. Germline polymorphisms play an important role in the treatment response of various human diseases, including bladder cancer. Intravesical BCG therapy is widely-used for bladder cancer.

Beyond diabetes mellitus: role of metformin in non-muscle-invasive bladder cancer.

Introduction: Usage of metformin is associated with improved survival in lung, breast and prostate cancer, and metformin has been shown to inhibit cancer cell growth and proliferation in in vitro studies. Given the lack of clinical data on metformin use in patients with bladder cancer, we aimed to evaluate the role of metformin in their oncological outcomes.

Methods: Medication use data from a prospectively maintained database of 122 patients with non-muscle-invasive bladder cancer treated with intravesical Bacille Calmette-Guerin (BCG), who were recruited under a randomised, double-blinded, controlled clinical trial, was collected and analysed.

Tryptophan-kynurenine ratio as a biomarker of bladder cancer.

Objectives: To investigate plasma and urinary kynurenine (KYN)-tryptophan (TRP) ratios in bladder cancer, expression of indoleamine 2,3-dioxygenase 1 (IDO1) in relation to tryptophan 2,3-dioxygenase (TDO2) in bladder tumour, and the correlation of KYN-TRP ratio with bladder tumour burden.

Methods: Metabotyping of the TRP-KYN metabolic axis was performed via a clinical case-control study. Expression of IDO1 and TDO2 was measured in human biopsied tissues.

and gene therapy improves the response to BCG immunotherapy in a murine model of bladder cancer.

To develop a strategy to improve response to bacillus Calmette-Gueri (BCG) using cytokine gene therapy ( + ). MB49-PSA tumor-bearing C57BL/6N mice were assigned into four groups: control; + therapy; BCG therapy or combined therapy ( + and BCG). In schedule 1, cytokine gene therapy was delivered before BCG therapy (eight instillations).

Receptor-Targeting Drug and Drug Carrier for Enhanced Killing Efficacy against Non-Muscle-Invasive Bladder Cancer.

Intravesical chemotherapy for bladder cancer has limited efficacy due to the lack of specificity of drugs/drug carriers toward the cancer cells as well as inadequate drug residence time in the bladder due to urine voiding. From analyses of surface receptor expression of UMUC3 bladder cancer cells and the targeting efficacy of different peptides, we selected a peptide (txCD47) that targets the cluster of differentiation 47 (CD47) surface protein overexpressed on these cells as a targeting ligand for docetaxel (DTX) and an albumin nanocarrier of DTX. The IC of DTX conjugated to txCD47 (txCD47-DTX) in a 1:1 molar ratio was lowered by a factor of 3 from that of free DTX.

Detection of Clinical Mesenchymal Cancer Cells from Bladder Wash Urine for Real-Time Detection and Prognosis.

Bladder cancer (BC) is a disease that requires lifelong surveillance due to its high recurrence rate. An efficient method for the non-invasive rapid monitoring of patient prognosis and downstream phenotype characterization is warranted. Here, we develop an integrated procedure to detect aggressive mesenchymal exfoliated bladder cancer cells (EBCCs) from patients in a label-free manner.

Dataset on gene expression in the elderly after Mindfulness Awareness Practice or Health Education Program.

It has been reported that relaxation techniques can improve physical health and cognitive function. A number of studies involving different types of relaxation practices showed changes in expression of genes. We investigated the gene expression pattern of a cohort of elderly subjects of Asian descent after weekly (for the first three months) and monthly (for the subsequent six months) intervention.

The Role of Vitamin D Receptor Polymorphisms in Predicting the Response to Therapy for Nonmuscle Invasive Bladder Carcinoma.

Purpose: Clinical and pathological predictors of bladder carcinoma recurrence and progression are relatively well defined. However, there is a paucity of genetic data specifically on the association of single nucleotide polymorphisms in specific genes for predicting recurrence and progression following immunotherapy. The VDR gene was found to regulate the immunomodulatory effects of vitamin D and it enhances the innate immunity system.

Bacillus Calmette-Guérin induces rapid gene expression changes in human bladder cancer cell lines that may modulate its survival.

Bacillus Calmette-Guérin (BCG) immunotherapy is the standard therapy for non-muscle invasive bladder cancer. The aim of the present study was to identify genes that are induced in response to BCG immunotherapy, as these may be potential biomarkers for the response to clinical therapy. To model clinical therapy, human bladder cancer cell lines were incubated with BCG (live or lyophilized BCG Connaught) for 2 h.

The liver-gut microbiota axis modulates hepatotoxicity of tacrine in the rat.

Unlabelled: The gut microbiota possesses diverse metabolic activities, but its contribution toward heterogeneous toxicological responses is poorly understood. In this study, we investigated the role of the liver-gut microbiota axis in underpinning the hepatotoxicity of tacrine. We employed an integrated strategy combining pharmacokinetics, toxicology, metabonomics, genomics, and metagenomics to elucidate and validate the mechanism of tacrine-induced hepatotoxicity in Lister hooded rats.

A Murine Orthotopic Bladder Tumor Model and Tumor Detection System.

This protocol describes the generation of bladder tumors in female C57BL/6J mice using the murine bladder cancer cell line MB49, which has been modified to secrete human Prostate Specific Antigen (PSA), and the procedure for the confirmation of tumor implantation. In brief, mice are anesthetized using injectable drugs and are made to lay in the dorsal position. Urine is vacated from the bladder and 50 µL of poly-L-lysine (PLL) is slowly instilled at a rate of 10 µL/20 s using a 24 G IV catheter.

Lactobacillus rhamnosus GG Activation of Dendritic Cells and Neutrophils Depends on the Dose and Time of Exposure.

This study evaluates the ability of Lactobacillus rhamnosus GG (LGG) to activate DC and neutrophils and modulate T cell activation and the impact of bacterial dose on these responses. Murine bone marrow derived DC or neutrophils were stimulated with LGG at ratios of 5 : 1, 10 : 1, and 100 : 1 (LGG : cells) and DC maturation (CD40, CD80, CD86, CD83, and MHC class II) and cytokine production (IL-10, TNF-α, and IL-12p70) were examined after 2 h and 18 h coculture and compared to the ability of BCG (the present immunotherapeutic agent for bladder cancer) to stimulate these cells. A 2 h exposure to 100 : 1 (high dose) or an 18 h exposure to 5 : 1 or 10 : 1 (low dose), LGG : cells, induced the highest production of IL-12 and upregulation of CD40, CD80, CD86, and MHC II on DC.

Local Immune Stimulation by Intravesical Instillation of Baculovirus to Enable Bladder Cancer Therapy.

Intravesical instillation of Bacillus Calmette-Guérin is currently used as adjuvant therapy for superficial, non-muscle invasive bladder cancer (NMIBC). However, nearly 40% of patients with NMIBC will fail Bacillus Calmette-Guérin therapy. In an attempt to investigate the feasibility of using insect baculovirus-based vectors for bladder cancer therapy, we observed that intravesical instillation of baculoviruses without transgene up-regulated a set of Th1-type of cytokines and increased the survival rate of mice bearing established orthotopic bladder tumors.