Search Results (218)

Bacteria-mediated cancer therapy represents a novel and promising strategy for targeted drug delivery to solid tumors. Multiple studies have demonstrated that various Bifidobacterium species can selectively colonize the hypoxic microenvironments characteristic of solid tumors. Leveraging this property, Bifidobacterium has been explored as a delivery vector for a range of anti-cancer approaches such as immunotherapy, nanoformulated chemotherapeutics, and gene therapy. Notably, anti-angiogenic genes such as endostatin and tumstatin have been successfully delivered to colorectal tumors using Bifidobacterium infantis and Bifidobacterium longum, respectively. Additionally, Bifidobacterium bifidum has been employed to transport doxorubicin and paclitaxel nanoparticles to breast and lung tumor sites. Furthermore, both Bifidobacterium longum and Bifidobacterium bifidum have been utilized to deliver nanoparticles that act as synergistic agents for high-intensity focused ultrasound (HIFU) therapy, significantly enhancing tumor ablation, particularly in triple-negative breast cancer (TNBC) models. While these pre-clinical findings are highly encouraging, further clinical research is essential. Specifically, studies are needed to investigate the colonization dynamics of different Bifidobacterium species across various tumor types and to evaluate their potential in delivering diverse cancer therapies in human patients. Full article

Colorectal liver metastasis (CRLM) poses a significant challenge in oncology due to its high incidence and poor prognosis in unresectable cases. Current treatments, including surgical resection, systemic chemotherapy, and liver-directed therapies, often fail to effectively target hypoxic tumor regions, which are inherently more resistant to these interventions. This review examines the potential of a novel therapeutic strategy combining irreversible electroporation (IRE) ablation and Clostridium novyi-nontoxic (C. novyi-NT) bacterial therapy. IRE is a non-thermal tumor ablation technique that uses high-voltage electric pulses to create permanent nanopores in cell membranes, leading to cell death while preserving surrounding structures, and is often associated with temporary tumor hypoxia due to disrupted perfusion. C. novyi-NT is an attenuated, anaerobic bacterium engineered to selectively germinate and proliferate in hypoxic tumor regions, resulting in localized tumor cell lysis while sparing healthy, oxygenated tissue. The synergy between IRE-induced hypoxia and hypoxia-sensitive C. novyi-NT may enhance tumor destruction and stimulate systemic antitumor immunity. Furthermore, the integration of advanced imaging and artificial intelligence can support precise treatment planning and real-time monitoring. This integrated approach holds promise for improving outcomes in patients with CRLM, though further preclinical and clinical validation is needed. Full article

This review explores current and emerging neuromodulation techniques targeting the cardiac autonomic nervous system for the treatment and prevention of atrial and ventricular arrhythmias. Arrhythmias remain a significant cause of morbidity and mortality, with the autonomic nervous system playing a crucial role in arrhythmogenesis. Interventions span surgical, pharmacological, and bioelectronic methods. We discuss the range of neuromodulation methods targeting the stellate ganglion, the spinal region, the parasympathetic system, and other promising methods. These include stellate ganglion block, stellate ganglion ablation, cardiac sympathetic denervation, subcutaneous electrical stimulation, thoracic epidural anesthesia, spinal cord stimulation, dorsal root ganglion stimulation, vagus nerve stimulation, baroreflex activation therapy, carotid body ablation, renal denervation, ganglionated plexi ablation, acupuncture, and transcutaneous magnetic stimulation. Both preclinical and clinical studies are presented as evidence for arrhythmia management. Full article

Objective: Radical therapies are associated with significant morbidity in patients with localized prostate cancer (PCa). While advances in nuclear magnetic resonance techniques have enabled the development of focal ablation procedures that can selectively destroy tumors, preserve the gland and surrounding structures, and minimize side effects, existing vascular-targeted photodynamic therapy (VTP) and nanodrug therapies often face limitations, such as recurrence and insufficient drug concentration at the tumor site. This study investigated a novel approach that combines VTP with systemic treatment using drug-loaded nanoparticles in a murine model, demonstrating substantial advancements beyond current monotherapies. Methods: SCID (severe combined immunodeficiency) mice were engrafted with androgen-sensitive prostate tumor cells (LNCaP-AR) and treated with a combination of VTP and two different drugs linked to fucoidan nanoparticles (Enzalutamide and Paclitaxel). Experiments were performed using different cohorts: the evaluation of oncological effect, the administration time and concentration of systemic therapy, a comparison of efficacy between VTP and radiotherapy, and the induction of the abscopal effect in untreated synchronous tumors. Results: The groups that received combination therapy showed better tumor control. After eight weeks, the recurrence-free survival rates were 87.5%, 62.5%, and 50% in the VTP + N-PAC, VTP + N-ENZ, and VTP monotherapy groups, respectively (p < 0.05). There was a significant difference in the intra-tumoral concentration of nanodrugs between the groups with combined treatment and monotherapy. After two weeks, the monotherapy groups showed almost total elimination of the drugs, whereas in the combined therapy groups, this concentration remained high, starting to decrease after three weeks (p < 0.05). Treatment with nanodrugs associated with VTP showed superior oncological benefits compared to radiotherapy alone or in combination with other therapies. The abscopal effect on synchronous tumors was not demonstrated with VTP alone or in combination with nanodrugs. Conclusions: Combining vascular photodynamic therapy with nanodrugs was highly effective in treating a prostate tumor model, leading to increased survival and a reduced risk of tumor recurrence. This approach significantly advances beyond existing VTP and nanodrug therapies by improving tumor control, ensuring sustained intra-tumoral drug concentration, and yielding superior oncological outcomes. Our results suggest that this therapy is a potential treatment option for prostate tumors treated with VTP in future clinical trials. Full article

In this study, we describe the preparation of carbon dots (CDs) from natural charcoal by laser ablation in a liquid. A continuum wave (CW) laser diode operating at a wavelength of 450 nm, hitting a solid carbon target placed into a biocompatible liquid, constituted of a phosphate-buffered saline (PBS) solution and distilled water, was used for the generation of the CDs suspension. Exploring the practical applications of carbon dots, it was observed that the luminescence of the produced CDs can be used as bioimaging in living organisms, environmental monitoring, chemical analysis, targeted drug delivery, disease diagnosis, therapy, and others. The CDs’ luminescence can be induced by UV irradiation and, as demonstrated in this study, by energetic MeV proton beams. The fluorescence was revealed mainly at 480 nm when UV illuminated the CDs, and also in the region at 514–642 nm when the CDs were irradiated by energetic proton ions. Atomic force microscopy (AFM) of the CD films revealed their spherical shape with a size of about 10 nm. The significance of the manuscript lies in the use of CDs produced by laser ablation exhibiting luminescence under irradiation of an energetic proton beam. Full article

Background: Atypical atrial flutter (AFL) is a complex clinical challenge, particularly in patients with prior atrial fibrillation (AF) treated with pulmonary vein isolation (PVI). Arrhythmias involving the vein of Marshall (VOM) often require extensive lesion sets, including ethanol infusion, to effectively target the epicardial substrate. To minimize tissue damage, an alternative strategy has been proposed, emphasizing advanced electroanatomical mapping, entrainment maneuvers, and highly targeted ablation techniques. Case Presentation: We describe a 72-year-old woman with recurrent atrial arrhythmias following pulmonary vein isolation (PVI), who presented with palpitations as her primary symptom. After ineffective pharmacological therapy, she underwent a catheter ablation procedure. Electroanatomical mapping revealed significant left atrial scarring and suggested a macroreentrant circuit involving the VOM. Entrainment maneuvers confirmed the VOM’s involvement. A single targeted endocardial ablation guided by the ablation index terminated the arrhythmia within 12 s, without the need for ethanol infusion or extensive lesion sets. Discussion: This case underscores the VOM’s role in sustaining atypical AFL post-PVI and highlights the effectiveness of precise electroanatomical mapping combined with targeted endocardial ablation. Unlike broader ablation or ethanol infusion strategies, a focused lesion at the critical isthmus achieved arrhythmia termination with minimal tissue damage. Conclusions: Endocardial ablation at the site of entrainment can safely and effectively treat VOM-related AFL, offering symptom relief and restoration of sinus rhythm. This approach may reduce procedural risks and expand the feasibility of VOM-related arrhythmia management in centers without access to ethanol infusion. Full article

Background: Chronic thoracic pain is commonly caused by thoracic facet dysfunction, intercostal neuralgia, surgery, or thoracic pain secondary to cancer and is present in approximately 15% of the population. Conventional treatments, including pharmacotherapy and transcutaneous electrical nerve stimulation, are often ineffective and are often associated with poorly tolerated adverse effects. Cooled radiofrequency ablation (c-RFA) is a minimally invasive procedure that uses radiofrequency energy delivered through a probe to lesion the targeted nerve and provide significant and lasting relief. Methods: This study was a retrospective analysis of data extracted from UW-Health Electronic Medical Health records from October 2015 through June 2024. Patient data were collected, including diagnosis, pre-operative pain score, post-operative pain score, duration of relief, age, sex, and BMI. A two-tailed paired t-test was used to analyze the pre-operative and post-operative pain scores. A p-value < 0.05 was considered significant. Results: A total of 111 thoracic c-RFA procedures were reviewed; 43 were excluded due to absent pre-operative or post-operative pain scores in medical records. A total of 68 procedures were included in the analysis, comprising 55 patients: 25 females and 30 males with an average age of 51.31 ± 18.22 years and a BMI of 29.79 ± 6.48 kg/m². Improvement in pain scores was reported in 77.94% (n = 53), 16.18% (n = 11) reported no change, and 5.88% (n = 4) reported worsening pain. Patients reported an average pre-operative pain score of 5.98 (M = 5.98, SD = 1.91) and an average post-operative pain score of 3.06 (M = 3.06, SD = 2.52); this achieved significance (p < 0.0001). Of the 77.94% (n = 53) charts that noted improvement, there is an average of 62.83 ± 28.48% reduction from their pre-operative pain scores. The average duration of relief lasted 11.85 ± 13.42 months. Conclusions: This study supports the efficacy and safety of c-RFA as a minimally invasive therapy for chronic thoracic pain refractory to conservative measures. Full article

Background and Objectives: Chronic pain is a significant global health issue, with conventional treatment strategies often proving insufficient or causing undesirable side effects. Interventional pain management techniques, including neuromodulation, have gained increasing interest as alternative therapeutic options. Cryoneurolysis, a technique leveraging extreme cold to modulate pain pathways, has emerged as a promising tool in chronic pain management. However, its efficacy and role within current clinical practice remain under evaluation. Methods: A narrative review was conducted by searching PubMed, Scopus, Embase, and Web of Science databases for studies published between 2010 and 2024 using the keywords “Cryoneurolysis”, “Cryoanalgesia”, “Cryoablation”, and “Chronic pain.” Only English-language studies were included. Studies that examined intraoperative cryoablation or lacked statistical analyses (except case reports) were excluded. Results: A total of 55 studies were included: 4 randomized controlled trials (RCTs), 16 retrospective studies, 4 prospective observational studies, and 31 case reports or small case series. The studies displayed significant heterogeneity in patient selection, targeted nerves, procedural protocols, and follow-up durations. While two RCTs demonstrated a significant pain reduction compared to control groups, other RCTs reported no significant improvement. Observational studies and case reports frequently report positive outcomes, with some achieving complete pain relief. Cryoneurolysis appears to be most effective in treating neuropathic pain, particularly in patients with peripheral nerve involvement. Conclusions: Cryoneurolysis is a safe technique for chronic pain management, which has been successfully applied, particularly for selected neuropathic pain conditions. However, the current evidence is limited by study heterogeneity and a lack of high-quality comparative trials. Further well-designed randomized studies are necessary to define its long-term efficacy and its potential role relative to other interventional pain therapies, such as radiofrequency ablation. Full article

Background/Objectives: The degree of vascularization of myomas plays an important role in both diagnosis and the selection of appropriate treatment. This is particularly relevant for minimally invasive therapies such as uterine artery embolization (UAE), high-intensity focused ultrasound (HIFU), or radiofrequency ablation (RFA) in uterine myomas, as their effectiveness is highest in well-vascularized lesions. This study aimed to analyze the perfusion of uterine myomas using dynamic contrast-enhanced magnetic resonance imaging and to develop a new quantitative classification of lesion vascularization, referencing the Funaki classification. Methods: The study included 56 female patients. Three parameters were determined for each lesion: the maximum signal enhancement (Ratio), time to peak, and mean signal intensity (Mean). A KMeans cluster analysis (k = 3) was performed, dividing the data into three groups corresponding to Funaki types I–III. Results: Significant differences were observed between the groups. Type III myomas were found only in older patients, which may be relevant when qualifying patients for vascularization-targeted therapies such as HIFU or radiofrequency ablation. Conclusions: The proposed classification may serve as a basis for automating the assessment of myomas and supporting clinical decision-making. Full article

Background/Objectives: Focal therapy (FT) and technology are closely connected. Advanced imaging allows for precise identification of the index lesion, enabling the targeted use of various thermal and non-thermal energy sources through different approaches, with specific techniques tailored to lesion location and operator expertise. This personalized approach enhances both safety and effectiveness, facilitating customized treatment planning. Methods: The International Consultation on Urological Diseases formed a committee to review the current literature on FT for prostate cancer (PCa), focusing specifically on the technique. Following in-depth discussions, the committee chose a “by lesion” approach rather than the traditional “by energy” approach to structure the review. A comprehensive PubMed search was conducted to gather relevant articles on the various energy modalities and procedural approaches used in FT for PCa. Results: Lesions in the apex, anterior, and posterior regions of the prostate can be accessed through several FT approaches, each associated with specific energy modalities and techniques. The transrectal approach utilizes high-intensity focused ultrasound (HIFU) and focal laser ablation (FLA), while the transperineal approach is compatible with energy sources such as cryotherapy, irreversible electroporation (IRE), brachytherapy, and FLA. The transurethral approach supports methods such as transurethral ultrasound ablation (TULSA). Each approach offers distinct advantages based on lesion location, treatment area, and energy modality. The choice of technique evaluated the safety and efficacy of each energy source and approach based on specific treatment areas within the prostate, highlighting the need for robust research across lesion locations and modalities, rather than focusing solely on each modality for a specific region. Conclusions: FT is rapidly advancing with new energy sources, technological improvements, and increasing operator expertise. To further optimize FT, research should prioritize evaluating the safety and effectiveness of different energy sources for various lesion locations, focusing on the treatment area rather than the energy modality itself. Full article

Thyroid cancer (TC) remains a prevalent malignancy, with over 820,000 global cases diagnosed in 2022. Differentiated thyroid carcinoma (DTC), primarily papillary and follicular types, accounts for most cases and has a favorable prognosis with total thyroidectomy and radioiodine (RAI) ablation. However, 5–15% of patients develop RAI-refractory (RAI-R) disease, leading to a significantly poorer outcome. For RAI-R patients, treatment decisions depend on disease progression. Active surveillance is suitable for indolent cases, while symptomatic or progressive disease requires systemic therapy. Multikinase inhibitors (MKIs) such as lenvatinib and sorafenib serve as first-line options, with cabozantinib recently approved for resistant cases. Additionally, novel targeted therapies, including RET and NTRK inhibitors, and immune checkpoint inhibitors, are under investigation, offering a personalized approach. A key challenge is determining the optimal timing for systemic therapy, balancing progression-free survival (PFS) benefits against MKI-related toxicities, which significantly impact quality of life (QoL). Molecular testing can identify actionable mutations, guiding therapy selection. Clinical guidelines (ATA, ESMO) recommend initiating treatment based on disease progression and patient condition, integrating strategies such as active surveillance, surgery, and radiotherapy when appropriate. Despite advances, systemic therapies carry significant adverse events (e.g., hypertension, fatigue, gastrointestinal toxicity), necessitating careful monitoring to prevent dose reductions or interruptions. A multidisciplinary approach is essential to optimize patient outcomes and maintain QoL. As targeted therapies continue to evolve, further research is needed to refine treatment sequencing and improve outcomes for RAI-R TC. This review synthesizes current evidence to guide clinical decision-making. Full article

As the adoption of focal therapy (FT) for prostate cancer (PCa) grows, the demand for accurate post-treatment imaging to monitor outcomes and detect residual or recurrent cancer increases. Traditional diagnostic systems like the Prostate Imaging Reporting and Data System (PI-RADS) are ill-suited for post-FT evaluations due to treatment-induced tissue changes. MRI-based scoring systems specific for evaluation after FT have been developed to address these challenges and improve post-FT imaging accuracy by distinguishing benign alterations from recurrence. The currently developed scoring systems are Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) and Prostate Imaging after Focal Ablation (PI-FAB). In this review, we describe and compare these two systems. These scoring systems standardize imaging assessments, enhance follow-up care, and support clinical decision-making. While promising, TARGET and PI-FAB require further large-scale validation to confirm their utility. Nevertheless, they represent critical advances in optimizing PCa management, particularly for patients undergoing FT, by improving diagnostic accuracy and guiding treatment decisions. Full article

Hypertrophic cardiomyopathy (HCM) is often associated with left ventricular outflow tract (LVOT) obstruction, which affects a substantial proportion of patients. This obstruction results from a range of anatomical abnormalities involving both the valvular and subvalvular structures. Pharmacological therapies play a pivotal role in the management of LVOT obstruction, with a range of drug classes exhibiting distinct mechanisms of action. Beta-blockers, including atenolol and nadolol, are considered the first-line treatment due to their ability to reduce heart rate and myocardial contractility and enhance diastolic filling. Non-dihydropyridine calcium channel blockers, such as verapamil and diltiazem, are utilized as second-line agents when beta-blockers are ineffective or contraindicated. Disopyramid, a Class 1A antiarrhythmic agent, is employed for patients who do not respond to initial therapeutic interventions and can reduce LVOT gradients. Recent advancements in cardiac myosin modulators, such as Mavacamten and Aficamten, offer targeted therapies by modulating myosin–actin interactions to reduce LVOT gradients and improve symptoms, with promising results from clinical trials. Although gene therapy is still in its nascent stages, it has the potential to address the genetic basis of HCM by employing techniques such as genome editing, gene replacement, and the modulation of signaling pathways. For patients exhibiting severe symptoms or demonstrating unresponsiveness to medical treatment, invasive therapies, such as septal reduction therapy and alcohol septal ablation, are considered. Ultimately, the treatment and prevention of atrial fibrillation and sudden cardiac death are two key points of HCM management in both obstructive and non-obstructive forms. This review aims to provide an overview of current pharmacological and invasive strategies, as well as emerging therapies, in the management of HCM. Full article

Antibody–drug conjugates (ADCs) are promising cancer therapeutics, but optimizing their cytotoxic payloads remains challenging. We present DumplingGNN, a novel hybrid Graph Neural Network architecture for predicting ADC payload activity and toxicity. Integrating MPNN, GAT, and GraphSAGE layers, DumplingGNN captures multi-scale molecular features using both 2D and 3D structural information. Evaluated on a comprehensive ADC payload dataset and MoleculeNet benchmarks, DumplingGNN achieves state-of-the-art performance, including BBBP (96.4% ROC-AUC), ToxCast (78.2% ROC-AUC), and PCBA (88.87% ROC-AUC). On our specialized ADC payload dataset, it demonstrates 91.48% accuracy, 95.08% sensitivity, and 97.54% specificity. Ablation studies confirm the hybrid architecture’s synergy and the importance of 3D information. The model’s interpretability provides insights into structure–activity relationships. DumplingGNN’s robust toxicity prediction capabilities make it valuable for early safety evaluation and biomedical regulation. As a research prototype, DumplingGNN is being considered for integration into Omni Medical, an AI-driven drug discovery platform currently under development, demonstrating its potential for future practical applications. This advancement promises to accelerate ADC payload design, particularly for Topoisomerase I inhibitor-based payloads, and improve early-stage drug safety assessment in targeted cancer therapy development. Full article

Hepatocellular carcinoma (HCC) is one of the leading causes of liver transplant worldwide. While liver transplantation offers a survival advantage for early-stage HCC patients, post-transplant recurrence remains a significant concern, affecting up to 15% of recipients. We sought to conduct a comprehensive review related to HCC recurrence after liver transplant. Tumor-related factors such as poor differentiation, vascular invasion, and elevated tumor biomarkers like alpha-fetoprotein are key predictors of recurrence. Donor-related factors, including graft type and surgical procedures, can also influence outcomes, though their effects are less conclusive. Advancements in patient selection criteria and scoring systems, such as the Milan Criteria and RETREAT score, have improved risk stratification by incorporating tumor size, biomarkers, and response to pre-transplant treatment. Despite these measures, recurrent HCC after transplantation poses treatment challenges. Curative approaches such as resection are feasible for localized or oligometastatic recurrence and offer the best outcomes when applicable. Locoregional treatments, including ablation and transarterial chemoembolization, provide options for unresectable cases but have limited long-term efficacy. Systemic therapies, including targeted agents like sorafenib, regorafenib, and lenvatinib, have shown modest benefits in managing advanced recurrent HCC. Emerging immunotherapy approaches hold promise but face unique challenges due to the required immunosuppression in transplant recipients. Multidisciplinary evaluation remains essential for tailoring treatment plans. Future efforts should focus on refining predictive tools and exploring novel therapies to improve survival outcomes for patients with recurrent HCC after liver transplantation. Full article