Nearly 20 million people are diagnosed with cancer each year with breast cancer being the most common among women. Triple negative breast cancer (TNBC), defined by its no/low expression of ER and PR and lack of amplification of HER2, makes up 15-20% of all breast cancer cases. While patients overall have a higher response to chemotherapy, this subgroup is associated with the lowest survival rate indicating significant clinical and molecular heterogeneity demanding alternate treatment options. Therefore, new therapies have been explored, with a large focus on utilizing the immune system. A whole host of immunotherapies have been studied including immune checkpoint inhibitors, now standard of care for eligible patients, and possibly the most exciting and promising is that of a TNBC vaccine. While currently there are no approved TNBC vaccines, this review highlights many promising studies and points to an antigen, p53, which we believe is highly relevant for TNBC.

Full-dose BCG bladder perfusion therapy is effective, but there are serious side effects. Whether a low dose of BCG can reduce the side effects of treatment while maintaining its efficacy is still inconclusive.

To compare the efficacy of low-dose and full-dose BCG bladder perfusion therapy and to provide reference for individual treatment of bladder cancer.

All relevant literature published in PubMed, Web of Science, and Embrase databases up to April 2024 was searched. The results and shortcomings of the existing literature are analyzed, the cognitive gaps between different studies are pointed out, and suggestions are made for future research.

A total of 32 pieces of literature were included. Twelve studies found that the efficacy of full-dose BCG perfusion was significantly better than that of low-dose BCG perfusion, and 20 studies found no statistical difference between low-dose and full-dose BCG perfusion CONCLUSION: Although there is no significant difference in the efficacy of full-dose and low-dose BCG in bladder perfusion, the trend indicates that the efficacy of full-dose BCG is still the most accurate. In cases where BCG resources are scarce or patients are intolerant, low-dose BCG bladder perfusion therapy may be an alternative to full-dose BCG bladder perfusion therapy. High-quality, large-sample prospective cohort studies (or randomized controlled studies) are still needed in the future.

This comprehensive review explores the evolving role of probiotic-based foods and beverages, highlighting their potential as functional and "future foods" that could significantly enhance nutrition, health, and overall well-being. These products are gaining prominence for their benefits in gut health, immune support, and holistic wellness. However, their future success depends on addressing critical safety concerns and navigating administrative complexities. Ensuring that these products "do more good than harm" involves rigorous evaluations of probiotic strains, particularly those sourced from the human gastrointestinal tract. Lactic acid bacteria (LABs) serve as versatile and effective functional starter cultures for the development of probiotic foods and beverages. The review emphasizes the role of LABs as functional starter cultures and the development of precision probiotics in advancing these products. Establishing standardized guidelines and transparent practices is essential, requiring collaboration among regulatory bodies, industry stakeholders, and the scientific community. The review underscores the importance of innovation in developing "friendly bacteria," "super probiotics," precision fermentation, and effective safety assessments. The prospects of functional probiotic-based foods and beverages rely on refining these elements and adapting to emerging scientific advancements. Ultimately, empowering consumers with accurate information, fostering innovation, and maintaining stringent safety standards will shape the future of these products as trusted and beneficial components of a health-conscious society. Probiotic-based foods and beverages, often infused with LABs, a "friendly bacteria," are emerging as "super probiotics" and "future foods" designed to "do more good than harm" for overall health.

To discuss the importance of educating healthcare professionals about oncological emergencies linked to novel systemic anticancer therapy (SACT) and the impact on acute oncology (AO) services.

This discussion is based on clinical expertise and informed by current literature.

Novel SACT, such as immune-checkpoint inhibitors, have more complex toxicity profiles and can be challenging to recognize and treat. An increasing prevalence of toxicity is expected as new drugs are developed and the numbers of patients living with and beyond cancer expand; more data are required to capture the full extent of this. There are knowledge gaps within the healthcare workforce, particularly outside oncology-specialist settings. Focused research in this area will provide direction for targeted educational interventions.

Insufficient SACT education is a safety issue; severe toxicities can be fatal but initial symptoms can be subtle and may be missed. We argue that emergency care pathways can help to streamline the appropriate management of patients with SACT toxicity, but awareness of AO issues remains "everyone's business." Continuing clinical education is key to maintaining awareness of newly developed SACT. AO service models may vary, but AO competence assessment passports can provide a standardized method of evidencing AO knowledge and skills.

Oncology nurses, as a highly specialized and knowledgeable part of the healthcare workforce, are key in supporting interprofessional education. By using existing cancer nursing frameworks, this can support the implementation of the AO Passports. The learning and development of AO services in the UK can be transferred internationally.

Bacteria-based vaccines have received increasing attention given the ability to induce strong systemic immune responses. However, the application of bacteria as therapeutic agents inevitably suffers from infection-associated side effects due to the living characteristics. Here, the use of bacteria-derived flagella is described to construct self-adjuvated nanofiber vaccines. With the help of charge-reversal mediated by decoration with cationic polymers, the flagella can be coated with negatively charged antigens through electrostatic interaction. By virtue of the large aspect ratio, the resulting nanofiber vaccines show prolonged retention at the injection site and increased uptake by dendritic cells and macrophages. Thanks to the innate immunogenicity, self-adjuvated flagella robustly promote dendritic cell maturation and macrophage polarization, resulting in the elicitation of antigen-specific T-cell and B-cell immune responses. In ovalbumin-overexpressing melanoma-bearing mice, immunization with ovalbumin-carried vaccines not only exhibits a favorable tolerance, but also displays superior inhibition efficacies on tumor growth and metastasis separately under the therapeutic and prophylactic settings. The flexibility of this approach is further demonstrated for vaccine fabrication by coating with the SARS-CoV-2 Spike protein S1 subunit. Bacterial flagella-based self-adjuvated nanofiber platform proposes a versatile strategy to develop various vaccines for disease prevention and treatment.

The most fatal side effect associated with revolutionary immune checkpoint inhibitor (ICI) cancer therapies is myocarditis, a rare and devastating complication with a mortality rate approaching 40%. This review comprehensively examines the limited knowledge surrounding this recently recognized condition, emphasizing the absence of evidence-based therapeutic strategies, diagnostic modalities, and reliable biomarkers that hinder effective management. It explores advancements in preclinical models that are uncovering disease mechanisms and enabling the identification of therapeutic targets. These efforts have informed the design of early clinical trials aimed at reducing mortality. With the growing prevalence of ICI therapies in oncology, addressing critical gaps, such as long-term outcomes and risk stratification, has become increasingly urgent. By synthesizing current evidence, this work seeks to enhance understanding and guide the development of strategies to improve patient outcomes and ensure the continued safe use of ICIs in cancer care.

Cell wall glycans isolated from microorganisms are long known to provoke strong immune responses piloted by innate immune cell populations, including monocytes, in the context of Trained Immunity (TI). However, the contribution of yeast-derived mannan in the reprogramming of monocytes remains ill-defined. Here, we demonstrated that TI is often accompanied by an altered gene expression profile of selected glycan-binding proteins expressed by monocytes, including DC-SIGN and Dectin-2. Additionally, we showed that mannan, a mannose rich glycan, can trigger an enhanced immune phenotype compatible with TI in healthy monocytes, with glycan-primed cells exhibiting enhanced pro-inflammatory cytokine secretion (TNFα and IL-6) and higher activation (CD86) levels. Furthermore, the glycan-mediated priming of monocytes also imposed alterations to the expression of certain Glycan-Binding Proteins, such as DC-SIGN. Importantly, we established that these mannan-trained immune cells displayed an improved capacity to kill tumor cells in vitro. Lastly, we confirmed that monocytes from non-muscle invasive bladder cancer patients treated with BCG instillations presented a TI phenotype, as was revealed by the higher cytokine production and activation. Altogether, this study lays the foundations for exploiting the immunological potential of glycan-derived pathogens in reprogramming innate immune cells towards an effective anti-tumor immune response.

Despite ongoing advancements, cancer remains a significant global health concern, with a persistent challenge in identifying a definitive cure. While various cancer therapies have been developed and approved, offering treatments for smaller neoplasms, their efficacy diminishes in solid tumors and hypoxic environments, particularly for chemotherapy and radiation therapy. A novel approach, Clostridium-based therapy, has emerged as a promising candidate for current solid tumor treatments due to its unique affinity for the hypoxic tumor microenvironment. This review examines the potential of Clostridium in cancer treatment, encompassing direct tumor lysis, immune modulation, and synergistic effects with existing cancer therapies. Advancements in synthetic biology have further enhanced its potential through genetic modifications, such as the removal of alpha toxin gene from Clostridium novyi-NT, the implementation of targeted approaches, and reduction in systemic toxicity. Although preclinical and clinical studies have demonstrated that Clostridium-based treatments combined with other therapies hold promise for complete cancer eradication, challenges persist. Through this review, we also propose that the integration of various methods and technologies together with Clostridium-based therapy may lead to the complete eradication of cancer in the future.

SUMMARYFor several decades, intravesical Bacillus Calmette-Guérin (iBCG) immunotherapy has been the gold standard adjuvant treatment for high-risk and selected intermediate-risk patients with non-muscle-invasive bladder cancer (NMIBC). In this review, the mechanisms of iBCG immune-mediated anti-cancer activity and resistance are presented. Furthermore, a literature review of short-term and systemic iBCG-related side effects was performed. A high incidence (75.5%) of iBCG-related short-term, self-limiting adverse events was observed, while more severe iBCG-related local/systemic complications (iBCG-rL/SCs) that required medical treatment or hospitalization occurred at a lower rate (2.35%). Disseminated was the most common form of iBCG-rSCs, while two-thirds of the cases were classified as infectious. The implementation of molecular-based techniques resulted in significantly higher diagnostic rates. Anti-tuberculous treatment (ATT) is the mainstay of treatment, while in patients with any iBCG-rL/SC form involving the vasculature, ATT should be combined with surgery. Local and osteoarticular forms have the lowest mortality, but their management necessitates severe and debilitating surgical procedures. The overall iBCG-attributed mortality in patients with iBCG-rL/SC was 7.4%, with disseminated, vascular, and lung involvements exhibiting the highest rates. Given the global shortage of BCG for the last two decades, as well as the paucity of effective options for iBCG-refractory or relapsing NMIBC patients, new therapeutic strategies are being tested with promising early results.

Intravesical Bacillus Calmette-Guérin (BCG) therapy is a gold standard for patients with high-risk non-muscle invasive bladder cancer (NMIBC). Although a long-lasting therapeutic response is observed in most patients, BCG failure occurs in 30%-50% of patients and a progression to muscle-invasive disease is found in 10%-15%. Therefore, predicting high-risk patients who might not benefit from BCG treatment is critical. The purpose of this study was to identify, whether the presence of specific oncogenic mutations might be indicative of BCG treatment response.

Nineteen high-grade NMIBC patients who received intravesical BCG were retrospectively enrolled and divided into "responders" and "non-responders" groups. Tissue samples from transurethral resection of bladder cancer were performed before starting therapy and were examined using a multigene sequencing panel.

Mutations in TP53, FGFR3, PIK3CA, KRAS, CTNNB1, ALK and DDR2 genes were detected. TP53 and FGFR3 were found to be the most frequently mutated genes in our cohort (31.6% and 26.3%, respectively), followed by PIK3CA (15.8%). In the BCG-responsive patient group, 90% of samples were found to have mutated genes, with almost 50% of them showing mutations in tyrosine kinase receptors and CTNNB1 genes. On the other hand, in the BCG-unresponsive group, we found mutations in 44.4% of samples, mainly in TP53 gene.

Our findings suggest that a Next-Generation Sequencing (NGS) multigene panel is useful in predicting BCG response in patients with NMIBC.

As a significant cause of global mortality, the cancer has also economic impacts. In the era of cancer therapy, mitigating side effects and costs and overcoming drug resistance is crucial. Microbial species can grow inside the tumor microenvironment and inhibit cancer growth through direct killing of tumor cells and immunoregulatory effects. Although microbiota or their products have demonstrated anticancer effects, the possibility of acting as pathogens and exerting side effects in certain individuals is a risk. Hence, several genetically modified/engineered bacteria (GEB) have been developed to this aim with ability of diagnosing and selective targeting and destruction of cancers. Additionally, GEB are expected to be considerably more efficient, safer, more permeable, less costly, and less invasive theranostic approaches compared to wild types. Potential GEB strains such as Escherichia coli (Nissle 1917, and MG1655), Salmonella typhimurium YB1 SL7207 (aroA gene deletion), VNP20009 (∆msbB/∆purI) and ΔppGpp (PTet and PBAD), and Listeria monocytogenes Lmat-LLO have been developed to combat cancer cells. When used in tandem with conventional treatments, GEB substantially improve the efficacy of anticancer therapy outcomes. In addition, public acceptance, optimal timing (s), duration (s), dose (s), and strains identification, interactions with other strains and the host cells, efficacy, safety and quality, and potential risks and ethical dilemmas include major challenges.

Myeloid cells, including macrophages, neutrophils, dendritic cells, and myeloid-derived suppressor cells, play crucial roles in the innate immune system, contributing to immune defense, tissue homeostasis, and organ development. They have tremendous potential as therapeutic tools for diseases such as cancer and autoimmune disorders, but harnessing cell engineering strategies to enhance potency and expand applications is challenging. Recent advancements in stem cell research have made it possible to differentiate human embryonic stem cells and induce pluripotent stem cells into various cell types, including myeloid cells, offering a promising new approach to generate myeloid cells for cell therapy. In this review, we explore the latest techniques for the genetic engineering of myeloid cells, discussing both established and emerging methodologies. We examine the challenges faced in this field and the therapeutic potential of engineered myeloid cells. We also describe examples of engineered macrophages, neutrophils, and dendritic cells in various disease contexts. By providing a detailed overview of the current state and future directions, we aim to highlight progress and ongoing efforts toward harnessing the full therapeutic potential of genetically engineered myeloid cells.

The BCG vaccine represents a significant milestone in the prevention of tuberculosis (TB), particularly in children. Researchers have been developing recombinant BCG (rBCG) variants that can trigger lasting memory responses, thereby enhancing protection against TB in adults. The breakdown of immune surveillance is a key link between TB and other communicable and non-communicable diseases. Notably, TB is more prevalent among people with comorbidities such as HIV, diabetes, cancer, influenza, COVID-19, and autoimmune disorders. rBCG formulations have the potential to address both TB and HIV co-pandemics. TB increases the risk of lung cancer and immunosuppression caused by cancer can reactivate latent TB infections. Moreover, BCG's efficacy extends to bladder cancer treatment and blood glucose regulation in patients with diabetes and TB. Additionally, BCG provides cross-protection against unrelated pathogens, emphasizing the importance of BCG-induced trained immunity in COVID-19 and other respiratory diseases. Furthermore, BCG reduced the severity of pulmonary TB-induced influenza virus infections. Recent studies have proposed innovations in BCG delivery, revaccination, and attenuation techniques. Disease-centered research has highlighted the immunomodulatory effects of BCG on TB, HIV, cancer, diabetes, COVID-19, and autoimmune diseases. The complex relationship between TB and comorbidities requires a nuanced re-evaluation to understand the shared attributes regulated by BCG. This review assessed the interconnected relationships influenced by BCG administration in TB and related disorders, recommending the expanded use of rBCG in healthcare. Collaboration among vaccine research stakeholders is vital to enhance BCG's efficacy against global health challenges.

Bladder cancer (BCa) remains a significant global health challenge, with increasing interest in the role of the bladder microbiome in its pathogenesis, progression and treatment outcomes. The complex relationship between bladder cancer and the microbiome, as well as the potential impact of probiotics on treatment effectiveness, is currently under investigation. Research suggests that the microbiota may influence BCa recurrence prevention and enhance the efficacy of the Bacillus Calmette-Guérin (BCG) vaccine. Recent studies reveal differences in the bladder microbiome between individuals without bladder cancer and those with the disease. In the healthy bladder, Streptococcus and Lactobacillus are consistently identified as the most prevalent genera. However, in men, the predominant bacterial genera are Staphylococcus, Corynebacterium and Streptococcus, while in women with bladder cancer, Gardnerella and Lactobacillus are dominant. Probiotics, particularly Lactobacillus spp., can exhibit anti-tumor properties by competing with pathogenic strains involved in carcinogenesis or by producing regulatory substances. They regulate cancer signaling, induce apoptosis, inhibit mutagenic activity, downregulate oncogene expression, induce autophagy, inhibit kinases, reactivate tumor suppressors and prevent metastasis. These mechanisms have shown promising results in both preclinical and some clinical studies.

Using synthetic biology techniques, bacteria have been engineered to serve as microrobots for diagnosing diseases and delivering treatments. These engineered bacteria can be used individually or in combination as microbial consortia. The components within these consortia complement each other, enhancing diagnostic accuracy and providing synergistic effects that improve treatment efficacy. The application of microbial therapies in cancer, intestinal diseases, and metabolic disorders underscores their significant potential. The impact of these therapies on the host's native microbiota is crucial, as engineered microbes can modulate and interact with the host's microbial environment, influencing treatment outcomes and overall health. Despite numerous advancements, challenges remain. These include ensuring the long-term survival and safety of bacteria, developing new chassis microbes and gene editing techniques for non-model strains, minimising potential toxicity, and understanding bacterial interactions with the host microbiota. This mini-review examines the current state of engineered bacteria and microbial consortia in disease diagnosis and treatment, highlighting advancements, challenges, and future directions in this promising field.

Adoptive T cell therapy, using T cell receptor-engineered T (TCR-T) cells and chimeric antigen receptor T (CAR-T) cells, is a potent immunotherapy option. Bladder cancer is a prevalent urological malignancy, particularly in cases of muscle invasion and metastasis, for which systemic therapy is crucial. Immunotherapy utilizing immune checkpoint blockade has been approved for bladder cancer treatment. The antitumor effect of an immune checkpoint blockade based on cytotoxic T cells (CTLs) and the patient's immune status is essential. The chemotherapeutic drug cisplatin (CDDP) is a key drug in bladder cancer treatment. However, it has been shown to suppress T cells, making combination therapy with CDDP and immunotherapy difficult. To address this, we developed TCR-T cells specific for bladder cancer cells. In previous studies, we found that the tumor-associated antigen CLSPN is overexpressed in CDDP-resistant bladder cancer cells and that the antigenic peptide HLA-A*02:01/CLSPN1254-1262, encoded by CLSPN, could be targeted by a CTL clone. The TCR was cloned from the HLA-A*02:01/CLSPN1254-1262 specific CTL clone yc3. We also designed a codon-optimized TCR sequence using GeneArt® GeneOptimizer® (Opt TCR) and compared the TCR-T cells using the original TCR sequence (Ori TCR-T cells) and the codon-optimized TCR sequence (Opt TCR-T cells). Opt TCR-T cells exhibited higher TCR transduction efficiency, higher TCR expression levels, higher avidity, and greater cytotoxicity than did Ori TCR-T cells. These results suggest that HLA-A*02:01/CLSPN1254-1262 specific Opt TCR-T cells are promising candidates for CDDP combination therapy.

Decades of basic and translational research have led to a momentum shift in dissecting the relationship between immune cells and cancer. This culminated in the emergence of breakthrough immunotherapies that paved the way for oncologists to manage certain hard-to-treat cancers. The application of high-throughput techniques of genomics, transcriptomics, and proteomics was conclusive in making and expediting the manufacturing process of cancer vaccines. Using the latest research technologies has also enabled scientists to interpret complex and multiomics data of the tumour mutanome, thus identifying new tumour-specific antigens to design new generations of cancer vaccines with high specificity and long-term efficacy. Furthermore, combinatorial regimens of cancer vaccines with immune checkpoint inhibitors have offered new therapeutic approaches and demonstrated impressive efficacy in cancer patients over the last few years. In the present review, we summarize the current state of cancer vaccines, including their potential therapeutic effects and the limitations that hinder their effectiveness. We highlight the current efforts to mitigate these limitations and highlight ongoing clinical trials. Finally, a special focus will be given to the latest milestones expected to transform the landscape of cancer therapy and nurture hope among cancer patients.

Combination therapy with checkpoint inhibitors blocks inhibitory immune cell signaling and improves clinical responses to anticancer treatments. However, continued development of innovative and controllable delivery systems for immune-stimulating agents is necessary to optimize clinical responses. Herein, we engineered Salmonella to deliver recombinant granulocyte macrophage colony stimulating factor (GM-CSF) in a controllable manner for combination treatment with a programmed death-ligand 1 (PD-L1) inhibitor. The engineered Salmonella enabled delivery of recombinant GM-CSF into mouse tumors, activating recruitment of immune cells, such as M1-polarized macrophages, dendritic cells, and CD8+ T cells. Combination treatment with the PD-L1 inhibitor and engineered Salmonella increased the survival rate of tumor-bearing mice by 25%. New tumor growth was strongly suppressed, and visible tumors disappeared at 120 days post-infection (dpi) in mice rechallenged with additional tumor implantation at 100 dpi. The number of memory T cells increased >2-fold in tumor-rechallenged mice. Our findings demonstrate superiority of the engineered Salmonella as a cancer therapeutic agent with precise targeting ability, immune-boosting activity, and ease of combination with other therapeutics.

Mycobacterium has presented public health challenges since its inception, primarily affecting developing nations. Much less is known about M. bovis, a member of the mycobacterium family more frequently affecting zoonotic species. Infections postaortic aneurysm repair are rare, and few cases have reported infection secondary to the lesser-known mycobacterium member, M. bovis. Here, we present a case of aortic graft infection status-post aortic aneurysm repair secondary to M. bovis. We highlight the essential role multi-modal radiographic imaging played in establishing this diagnosis.

The intricate tumor microenvironment presents formidable obstacles to the efficacy of adoptive T cell therapy in the management of solid tumors by limiting the infiltration and inducing exhaustion of the transferred T cells. Here, we developed a bacterial-based adjuvant approach that augments the efficacy of adoptive T-cell therapy for solid tumor treatment. Our study reveals that intratumor injection of E. coli MG1655 normalizes tumor vasculatures and reprograms tumor-associated macrophages into M1 phenotype that produce abundant CCL5, together facilitating tumor infiltration of adoptively transferred T cells. The depletion of tumor-associated macrophages or CCL5 neutralization in vivo leads to the significantly decreased solid tumor infiltration of adoptive T cells in the presence of bacteriotherapy. This combinatorial therapy, consisting of E. coli adjuvant and adoptive T-cell therapy, effectively eradicates early-stage melanoma and inhibits the progression of pancreatic tumors. Notably, this dual strategy also strengthened the distal tumor control capabilities of adoptive T-cell therapy through the induction of in situ tumor vaccination. This dual therapeutic approach involving bacterial therapy targeting the interior of solid tumors and adoptive T-cell therapy attacking the tumor periphery exhibits potent therapeutic efficacy in achieving the eradication of advanced-stage tumors, including melanoma and hepatocellular carcinoma, by converging attacks from both inside and outside the tumor tissues.

Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of urothelial cancers and is associated with high morbidity and mortality. Increasing incidence of UTUC has been observed since the 1970's, alongside the evolution of advance imaging techniques, precision biopsy equipment, and risk stratification models. The high morbidity of radical nephroureterectomy (RNU) which is still the gold-standard treatment for high-risk UTUC, has driven the development of kidney-sparing surgery alternatives for low-risk UTUC. Now, several treatment approaches have outcomes comparable to RNU for low-risk UTUC and guidelines are recommending kidney-sparing surgery for favorable low-risk disease. The main categories of kidney-sparing surgery include segmental ureterectomy, endoscopic ablation, chemoablation, and vascular-targeted phototherapy. These treatments are highly nuanced making them difficult to compare, but for most cases of favorable low-grade disease, we recommend endoscopic laser ablation with optional adjuvant intracavitary therapy. Adverse events associated with kidney-sparing surgery include ureteral stricture, bleeding requiring transfusion, and bladder recurrence of UTUC. Limitations of kidney-sparing surgery include appropriate tissue sampling (contributing to under-grading and under-staging), higher rates of ipsilateral recurrence, and potential for grade and stage progression. Collectively, these may subsequently necessitate RNU. Here, we review the technical variations and evidence behind kidney-sparing therapies as well as their practicality in the real world.

This study aimed to describe the life impacts of intravesical therapies for non-muscle invasive bladder cancer (NMIBC) from a patient perspective.

A cross-sectional online survey design was used. Adults with NMIBC (and no other cancer) treated intravesically in the prior 12 months were recruited from US patient online communities. Individuals participating in a clinical trial or treated with erdafitinib were excluded. Participants' treatment experiences were evaluated using a questionnaire comprising (a) custom questions reported on 11-point numerical rating scales and (b) validated patient reported outcome (PRO) measures for bladder symptom burden and work productivity.

Among 171 survey participants, most received bacillus Calmette-Guérin (BCG) (83%), intravesical gemcitabine (28%), or gemcitabine + docetaxel (13%) during the past year. Participants generally felt adequately informed about treatment, felt expectation of treatment matched actual experience, and expressed intent to complete the full treatment course and willingness to try different treatments if needed. Participants reported disease symptom burden of 42.6/72 on the NFBlSI-18 scale. Employed participants reported 51% work impairment and 59% overall work productivity loss due to NMIBC.

Participants recently treated with intravesical therapies expressed intent to complete the full treatment course and willingness to try new therapies if needed. Participants reported high NMIBC symptom burden and work impairment negatively impacting their well-being, despite receiving intravesical treatment.

Treatments targeting the immune system only benefit a subset of patients with bladder cancer (BC). Biomarkers predictive of BC progression and response to specific therapeutic interventions are required. We evaluated whether peripheral blood immune subsets and expression of clinically relevant immune checkpoint markers are associated with clinicopathologic features of BC. Peripheral blood mononuclear cells isolated from blood collected from 23 patients with BC and 9 age-matched unaffected-by-cancer control donors were assessed using a 21-parameter flow cytometry panel composed of markers of T, B, natural killer and myeloid populations and immune checkpoint markers. Patients with BC had significantly lower numbers of circulating CD19+ B cells and elevated circulating CD4+CD8+ T cells compared with the control cohort. Immune checkpoint markers programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) were elevated in the total peripheral immune cell population in patients with BC. Within the BC cohort, PD-1 expression in T and myeloid cells was elevated in muscle-invasive compared with non-muscle-invasive disease. In addition, elevated T, B and myeloid PD-1 cell surface expression was significantly associated with tumor stage, suggesting that measures of peripheral immune cell exhaustion may be a predictor of tumor progression in BC. Finally, positive correlations between expression levels of the various immune checkpoints both overall and within key peripheral blood immune subsets collected from patients with BC were observed, highlighting likely coregulation of peripheral immune checkpoint expression. The peripheral blood immunophenotype in patients with BC is altered compared with cancer-free individuals. Understanding this dysregulated immune profile will contribute to the identification of diagnostic and prognostic indicators to guide effective immune-targeted, personalized treatments.

Photodynamic therapy (PDT) initially employed red light, which caused some patients to experience permanent bladder contractions. PDT using the FDA-approved drug hexaminolevulinate (HAL), which produces protoporphyrin IX (PpIX) in the tumor, showed some promise but has low efficacy in treating non-muscle-invasive bladder cancer (NMIBC). We developed singlet oxygen-activatable prodrugs of two anticancer drugs, paclitaxel and mitomycin C, to enhance the antitumor effect of PpIX-PDT without producing systemic side effects, by promoting only local release of the active chemotherapeutic agent. Orthotopic NMIBC model was used to compare the efficacy of prodrugs only, PpIX-PDT, and prodrugs + PpIX-PDT. 532 nm laser with a total power of 50 mW for 20 min (60 J, single treatment) was used with HAL and prodrugs. Histology and microscopic methods with image analysis were used to evaluate the tumor staging, antitumor efficacy, and local toxicity. Prodrug + PpIX-PDT produced superior antitumor efficacy than PpIX-PDT alone with statistical significance. Both PpIX-PDT alone and combination therapy resulted in mild damage to the bladder epithelium in the normal bladder area with no apparent damage to the muscle layer. Overall, SO-cleavable prodrugs improved the antitumor efficacy of PpIX-PDT without causing severe and permanent damage to the bladder muscle layer.

Mitochondria play an essential role in cancer treatment by providing apoptotic signals. Hexyl aminolevulinate, an FDA-approved diagnosis for non-muscle invasive bladder cancer, induces the production of protoporphyrin IX (PpIX) preferentially by mitochondria in cancer cells. Photosensitizer PpIX upon illumination can release active chemotherapy drugs from singlet oxygen-activatable prodrugs. Prodrugs placed close enough to PpIX formed in mitochondria can improve the antitumor efficiency of PpIX-PDT. The preferred uptake of prodrugs by cancer cells and tumors can further enhance the selective damage of cancer cells over non-cancer cells and surrounding normal tissues. Mitochondriotropic prodrugs of anticancer drugs, such as paclitaxel and SN-38, were synthesized using rhodamine, a mitochondrial-targeting moiety. In vitro, the mitochondrial targeting helped achieve preferential cellular uptake in cancer cells. In RT112 cells (human bladder cancer cells), intracellular prodrug concentrations were 2-3 times higher than the intracellular prodrug concentrations in BdEC cells (human bladder epithelial cells), after 2 h incubation. In an orthotopic rat bladder tumor model, mitochondria-targeted prodrugs achieved as much as 34 times higher prodrug diffusion in the tumor area compared to the nontumor bladder area. Overall, mitochondria targeting made prodrugs more effective in targeting cancer cells and tumors over non-tumor areas, thereby reducing nonspecific toxicity.

Bacillus Calmette-Guërin (BCG) has been traditionally used as a vaccine against tuberculosis (TB), which contains live, attenuated strain of Mycobacterium bovis. However, intravesical BCG administration has been used as an immunological treatment of superficial bladder cancer. Complications after bladder instillation of BCG are rare. We report a case of carcinoma urinary bladder with histopathologically proven granulomatous epididymo-orchitis (TB) after treatment with intravesical BCG.

Bacillus species have attracted significant attention in recent years due to their potential for producing various bioactive compounds with diverse functional properties. This review highlights bioactive substances from food-grade Bacillus strains and their applications in functional foods and nutraceuticals. The metabolic capacities of Bacillus species have allowed them to generate a wide range of bioactive substances, including vitamins, enzymes, anti-microbial peptides, and other non-ribosomal peptides. These substances have a variety of positive effects, including potential cholesterol-lowering and immune-modulatory qualities in addition to anti-oxidant and anti-bacterial actions. The uses and mechanisms of action of these bioactive chemicals can be used to improve the functional qualities and nutritional profile of food products. Examples include the use of anti-microbial peptides to increase safety and shelf life, as well as the use of Bacillus-derived enzymes in food processing to improve digestibility and sensory qualities. The exploitation of bioactive compounds from food-grade Bacillus strains presents a promising frontier in the development of functional foods and nutraceuticals with enhanced health benefits. Due to their wide range of activity and applications, they are considered as important resources for the development of novel medications, agricultural biocontrol agents, and industrial enzymes. Ongoing research into the biosynthetic pathways, functional properties, and applications of these compounds is essential to fully realize their potential in the food industry. This review underscores the significance of various bioactive compounds generated from Bacillus in tackling global issues like environmental sustainability, sustainable agriculture, and antibiotic resistance. Future developments in microbiology and biotechnology will enable us to fully utilize the potential of these amazing microbes, resulting in novel approaches to industry, agriculture, and health. © 2024 Society of Chemical Industry.

The BCG vaccine, Bacille Calmette Guerin, holds the distinction of being the most widely administered vaccine. Remarkably, a century has passed since its discovery; however, puzzlingly, questions persist regarding the effectiveness of the immune response it triggers. After years of diligent observation, it has been deduced that BCG imparts immunity primarily to a specific age group, namely children. This prompts a significant query: the rationale behind BCG's limited efficacy against TB in particular age groups and populations remains elusive. Beyond vaccinations, drug therapy has emerged as an alternative route for TB prevention. Nonetheless, this approach faces challenges in the contemporary landscape, marked by the emergence of new instances of MDR-TB and XDR-TB, compounded by the financial burden of treatment. It's noteworthy that BCG remains the sole WHO-approved vaccine for TB. This comprehensive review delves into several aspects, encompassing the immune response during infection, the shortcomings of BCG in conferring immunity, and the various factors contributing to its limitations. Within this discourse, we explore potential explanations for the observed deficiencies of the BCG vaccine and consider how these insights could catalyze the development of future vaccines. The current landscape of novel vaccine development for TB is illuminated, including a spotlight on the latest vaccine candidates.

Conventional cancer therapies, including chemotherapy, radiotherapy, and immunotherapy, have significantly advanced cancer treatment. However, these modalities often face limitations such as systemic toxicity, lack of specificity, and the emergence of resistance. Recent advancements in genetic engineering and synthetic biology have rekindled interest in using bacteria as a novel therapeutic approach in oncology. This comprehensive review explores the potential of microbial therapeutics, particularly bacterial therapies, in the treatment of cancer. Bacterial therapies offer several unique advantages, such as the ability to selectively target and colonize hypoxic and necrotic regions of tumors, areas typically resistant to conventional treatments. The review delves into the mechanisms through which bacteria exert antitumor effects, including direct tumor cell lysis, modulation of the immune response, and delivery of therapeutic agents like cytotoxins and enzymes. Various bacterial species, such as Salmonella, Clostridium, Lactobacillus, and Listeria, have shown promise in preclinical and clinical studies, demonstrating diverse mechanisms of action and therapeutic potential. Moreover, the review discusses the challenges associated with bacterial therapies, such as safety concerns, immune evasion, and the need for precise targeting, and how recent advances in genetic engineering are being used to overcome these hurdles. Current clinical trials and combination strategies with conventional therapies are also highlighted to provide a comprehensive overview of the ongoing developments in this field. In conclusion, while bacterial therapeutics present a novel and promising avenue in cancer treatment, further research and clinical validation is required to fully realize their potential. This review aims to inspire further exploration into microbial oncology, paving the way for innovative and more effective cancer therapies.

The tumor microenvironment (TME) is a critical determinant in the initiation, progression, and treatment outcomes of various cancers. Comprising of cancer-associated fibroblasts (CAF), immune cells, blood vessels, and signaling molecules, the TME is often likened to the soil supporting the seed (tumor). Among its constituents, tumor-associated macrophages (TAMs) play a pivotal role, exhibiting a dual nature as both promoters and inhibitors of tumor growth. This review explores the intricate relationship between TAMs and the TME, emphasizing their diverse functions, from phagocytosis and tissue repair to modulating immune responses. The plasticity of TAMs is highlighted, showcasing their ability to adopt either protumorigenic or anti-tumorigenic phenotypes based on environmental cues. In the context of cancer, TAMs' pro-tumorigenic activities include promoting angiogenesis, inhibiting immune responses, and fostering metastasis. The manuscript delves into therapeutic strategies targeting TAMs, emphasizing the challenges faced in depleting or inhibiting TAMs due to their multifaceted roles. The focus shifts towards reprogramming TAMs to an anti-tumorigenic M1-like phenotype, exploring interventions such as interferons, immune checkpoint inhibitors, and small molecule modulators. Noteworthy advancements include the use of CSF1R inhibitors, CD40 agonists, and CD47 blockade, demonstrating promising results in preclinical and clinical settings. A significant section is dedicated to Chimeric Antigen Receptor (CAR) technology in macrophages (CAR-M cells). While CAR-T cells have shown success in hematological malignancies, their efficacy in solid tumors has been limited. CAR-M cells, engineered to infiltrate solid tumors, are presented as a potential breakthrough, with a focus on their development, challenges, and promising outcomes. The manuscript concludes with the exploration of third-generation CAR-M technology, offering insight into in-vivo reprogramming and nonviral vector approaches. In conclusion, understanding the complex and dynamic role of TAMs in cancer is crucial for developing effective therapeutic strategies. While early-stage TAM-targeted therapies show promise, further extensive research and larger clinical trials are warranted to optimize their targeting and improve overall cancer treatment outcomes.

Bladder cancer is a leading cancer type in men. The complexity of treatment in late-stage bladder cancer after systemic spread through the lymphatic system highlights the importance of modulating disease-free progression as early as possible in cancer staging. With current therapies relying on previous standards, such as platinum-based chemotherapeutics and immunomodulation with Bacillus Calmette-Guerin, researchers, and clinicians are looking for targeted therapies to stop bladder cancer at its source early in progression. A new era of molecular therapies that target specific features upregulated in bladder cancer cell lines is surfacing, which may be able to provide clinicians and patients with better control of disease progression. Here, we discuss multiple emerging therapies including immune checkpoint inhibitors of the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway, antibody-drug conjugates, modulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) cell proliferation pathway, chimeric antigen receptor T-cell therapy, and fibroblast growth factor receptor targeting. Together, these modern treatments provide potentially promising results for bladder cancer patients with the possibility of increasing remission and survival rates.

Problems, such as toxic side effects and drug resistance of chemoradiotherapy, target therapy and immunotherapy accompanying the current anti-cancer treatments, have become bottlenecks limiting the clinical benefit for patients. Therefore, it is urgent to find promising anti-cancer strategies with higher efficacy and lesser side effects. Baicalein, a flavonoid component derived from the Chinese medicine scutellaria baicalensis, has been widely studied for its remarkable anti-cancer activity in multiple types of malignancies both at the molecular and cellular levels. Baicalein exerts its anti-tumor effects by inhibiting angiogenesis, invasion and migration, inducing cell apoptosis and cell cycle arrest, as well as regulating cell autophagy, metabolism, the tumor microenvironment and cancer stem cells with no obvious toxic side effects. The role of classic signaling pathways, such as PI3K/AKT/mTOR, MAPK, AMPK, Wnt/β-catenin, JAK/STAT3, MMP-2/-9, have been highlighted as the major targets for baicalein exerting its anti-malignant potential. Besides, baicalein can regulate the relevant non-coding RNAs, such as lncRNAs, miRNAs and circ-RNAs, to inhibit tumorigenesis and progression. In addition to the mentioned commonalities, baicalein shows some specific anti-tumor characteristics in some specific cancer types. Moreover, the preclinical studies of the combination of baicalein and chemoradiotherapy pave the way ahead for developing baicalein as an adjunct treatment with chemoradiotherapy. Our aim is to summary the role of baicalein in different types of cancer with its mechanisms based on in vitro and in vivo experiments, hoping providing proof for baicalein serving as an effective and safe compound for cancer treatment in clinic in the future.

As more is learned about the benefits of microbes, their potential to prevent and treat disease is expanding. Microbial therapeutics are less burdensome and costly to produce than traditional molecular drugs, often with superior efficacy. Yet, as with most medicines, controlled dosing and delivery to the area of need remain key challenges for microbes. Advances in materials to control small-molecule delivery are expected to translate to microbes, enabling similar control with equivalent benefits. In this perspective, recent advances in living biotherapeutics are discussed within the context of new methods for their controlled release. The integration of these advances provides a roadmap for the design, synthesis, and analysis of controlled microbial therapeutic delivery systems.

The frequent zoonotic disease known as "bovine tuberculosis" is brought on by the Mycobacterium bovis bacteria, which can infect both people and animals. The aim of this review article is to provide an explanation of the etiology, history, epidemiology, pathogenesis, clinical symptoms, diagnosis, transmission, risk factors, public health importance, economic impact, treatment, and control of bovine tuberculosis. Primarily, bovine tuberculosis affects cattle, but other animals may also be affected. Bovine tuberculosis is present throughout the world, with the exception of Antarctica. Cattle that contract bovine tuberculosis might suffer from a persistent, crippling illness. In the early stages of the disease, there are no symptoms. The tuberculin test is the primary method for detecting bovine tuberculosis in cows. Depending on its localized site in the infected animal, M. bovis can be found in respiratory secretions, milk, urine, feces, vaginal secretions, semen, feces, and exudates from lesions (such as lymph node drainage and some skin lesions). This illness generally lowers cattle productivity and could have a negative financial impact on the livestock business, particularly the dairy industry. The most effective first-line anti-tuberculosis chemotherapy consists of isoniazid, ethambutol, rifampin, and streptomycin. Second-line drugs used against bovine tuberculosis include ethionamide, capreomycin, thioacetazone, and cycloserine. To successfully control and eradicate bovine tuberculosis, developed nations have implemented routine testing and culling of infected animals under national mandatory programs.

Dendritic cells (DCs) are a heterogeneous group of antigen-presenting innate immune cells that regulate adaptive immunity, including against cancer. Therefore, understanding the precise activities of DCs in tumours and patients with cancer is important. The classification of DC subsets has historically been based on ontogeny; however, single-cell analyses are now additionally revealing a diversity of functional states of DCs in cancer. DCs can promote the activation of potent antitumour T cells and immune responses via numerous mechanisms, although they can also be hijacked by tumour-mediated factors to contribute to immune tolerance and cancer progression. Consequently, DC activities are often key determinants of the efficacy of immunotherapies, including immune-checkpoint inhibitors. Potentiating the antitumour functions of DCs or using them as tools to orchestrate short-term and long-term anticancer immunity has immense but as-yet underexploited therapeutic potential. In this Review, we outline the nature and emerging complexity of DC states as well as their functions in regulating adaptive immunity across different cancer types. We also describe how DCs are required for the success of current immunotherapies and explore the inherent potential of targeting DCs for cancer therapy. We focus on novel insights on DCs derived from patients with different cancers, single-cell studies of DCs and their relevance to therapeutic strategies.

Despite decades of research, cancer continues to be a major global health concern. The human mouth appears to be a multiplicity of local environments communicating with other organs and causing diseases via microbes. Nowadays, the role of oral microbes in the development and progression of cancer has received increasing scrutiny. At the same time, bioengineering technology and nanotechnology is growing rapidly, in which the physiological activities of natural bacteria are modified to improve the therapeutic efficiency of cancers. These engineered bacteria were transformed to achieve directed genetic reprogramming, selective functional reorganization and precise control. In contrast to endotoxins produced by typical genetically modified bacteria, oral flora exhibits favorable biosafety characteristics. To outline the current cognitions upon oral microbes, engineered microbes and human cancers, related literatures were searched and reviewed based on the PubMed database. We focused on a number of oral microbes and related mechanisms associated with the tumor microenvironment, which involve in cancer occurrence and development. Whether engineering oral bacteria can be a possible application of cancer therapy is worth consideration. A deeper understanding of the relationship between engineered oral bacteria and cancer therapy may enhance our knowledge of tumor pathogenesis thus providing new insights and strategies for cancer prevention and treatment.

Bladder cancer is a heterogeneous disease. Treatment decisions are mostly decided based on disease stage (non-muscle invasive or muscle invasive). Patients with muscle-invasive disease will be offered a radical treatment combined with systemic therapy, while in those with non-muscle-invasive disease, an attempt to resect the tumor endoscopically will usually be followed by different intravesical instillations. The goal of intravesical therapy is to decrease the recurrence and/or progression of the tumor. In the current landscape of bladder cancer treatment, BCG is given intravesically to induce an inflammatory response and recruit immune cells to attack the malignant cells and induce immune memory. While the response to BCG treatment has changed the course of bladder cancer management and spared many "bladders", some patients may develop BCG-unresponsive disease, leaving radical surgery as the best choice of curative treatment. As a result, a lot of effort has been put into identifying novel therapies like systemic pembrolizumab and Nadofaragene-Firadenovac to continue sparing bladders if BCG is ineffective. Moreover, recent logistic issues with BCG production caused a worldwide BCG shortage, re-sparking interest in alternative BCG treatments including mitomycin C, sequential gemcitabine with docetaxel, and others. This review encompasses both the historic and current role of BCG in the treatment of non-muscle-invasive bladder cancer, revisiting BCG alternative therapies and reviewing the novel therapeutics that were approved for the BCG-unresponsive stage or are under active investigation.

We aimed to compare the efficacy and adverse events of Bacillus Calmette-Guérin (BCG) versus Mitomycin C (MMC) in high-risk Non-Muscle-Invasive Bladder Cancer (NMIBC) patients.

This randomized controlled study was conducted over 24 months in four hospitals in Egypt. A sample of 90 patients was randomly assigned to either treatment group, with procedures including baseline examinations, a single postoperative instillation of chemotherapy, a 6-week induction cycle of the assigned drug, and regular follow-up cystoscopies and upper urinary tract imaging. Treatment results and side effects were monitored, with data analyzed via Statistical Package for Social Sciences (SPSS).

No significant differences were observed in mean age or tumor characteristics (p > 0.05). However, adverse reactions were significantly higher in the BCG group, including cystitis (40% vs. 17.78%, p = 0.020), hematuria (24.44% vs. 4.44%, p = 0.007), overall local reactions (75.56% vs. 26.67%, p < 0.001), fever (13.33% vs. 2.22%, p = 0.049), and fatigue (17.78% vs. 2.22%, p = 0.014). The MMC group had a slightly higher recurrence rate (28.89% vs. 17.78%, hazard ratio 1.89, 95% CI: 0.78-4.55, p = 0.15) with a shorter median time to recurrence (six vs. 12 months). Progression rates were similar (8.89% MMC vs. 4.44% BCG, p = 0.398).

Although BCG and MMC have comparable efficacy in managing high-risk NMIBC, BCG demonstrated a higher rate of adverse reactions. Decision-making should consider this balance, patient preferences, and health status. Further research is needed for the validation and exploration of these findings.

Despite the availability of technological advances in traditional anti-cancer therapies, there is a need for more precise and targeted cancer treatment strategies. The wide-ranging shortfalls of conventional anticancer therapies such as systematic toxicity, compromised life quality, and limited to severe side effects are major areas of concern of conventional cancer treatment approaches. Owing to the expansion of knowledge and technological advancements in the field of cancer biology, more innovative and safe anti-cancerous approaches such as immune therapy, gene therapy and targeted therapy are rapidly evolving with the aim to address the limitations of conventional therapies. The concept of immunotherapy began with the capability of coley toxins to stimulate toll-like receptors of immune cells to provoke an immune response against cancers. With an in-depth understating of the molecular mechanisms of carcinogenesis and their relationship to disease prognosis, molecular targeted therapy approaches, that inhibit or stimulate specific cancer-promoting or cancer-inhibitory molecules respectively, have offered promising outcomes. In this review, we evaluate the achievement and challenges of these technically advanced therapies with the aim of presenting the overall progress and perspective of each approach.

Non-muscle invasive bladder cancer (NMIBC) accounts for ~70-75% of total bladder cancer tumors and requires effective early intervention to avert progression. The cornerstone of high-risk NMIBC treatment involves trans-urethral resection of the tumor followed by intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. However, BCG therapy is commonly accompanied by significant lower urinary tract symptoms (LUTS) including urinary urgency, urinary frequency, dysuria, and pelvic pain which can undermine treatment adherence and clinical outcomes. Despite this burden, the mechanisms underlying the development of BCG-induced LUTS have yet to be characterized. This review provides a unique perspective on the mechanisms thought to be responsible for the development of BCG-induced LUTS by focussing on the sensory nerves responsible for bladder sensory transduction. This review focuses on how the physiological response to BCG, including inflammation, urothelial permeability, and direct interactions between BCG and sensory nerves could drive bladder afferent sensitization leading to the development of LUTS. Additionally, this review provides an up-to-date summary of the latest clinical data exploring interventions to relieve BCG-induced LUTS, including therapeutic targeting of bladder contractions, inflammation, increased bladder permeability, and direct inhibition of bladder sensory signaling. Addressing the clinical burden of BCG-induced LUTS holds significant potential to enhance patient quality of life, treatment compliance, and overall outcomes in NMIBC management. However, the lack of knowledge on the pathophysiological mechanisms that drive BCG-induced LUTS has limited the development of novel and efficacious therapeutic options. Further research is urgently required to unravel the mechanisms that drive BCG-induced LUTS.

The imbalance of microbial composition and diversity in favor of pathogenic microorganisms combined with a loss of beneficial gut microbiota taxa results from factors such as age, diet, antimicrobial administration for different infections, other underlying medical conditions, etc. Probiotics are known for their capacity to improve health by stimulating the indigenous gut microbiota, enhancing host immunity resistance to infection, helping digestion, and carrying out various other functions. Concurrently, the metabolites produced by these microorganisms, termed postbiotics, which include compounds like bacteriocins, lactic acid, and hydrogen peroxide, contribute to inhibiting a wide range of pathogenic bacteria. This review presents an update on using probiotics in managing and treating various human diseases, including complications that may emerge during or after a COVID-19 infection.