Prostate cancer (PRAD) progression varies significantly among patients, with metabolic reprogramming linked to oncogenesis and immune response. However, the prognostic and immune-related roles of metabolic reprogramming-related genes (MRGs) in PRAD remain unclear. PRAD transcriptomic, mutation, and clinical data from TCGA were analyzed. WGCNA identified PRAD-associated gene modules. NMF clustering stratified patients into two molecular subgroups. Prognostic MRGs were screened via univariate Cox and LASSO regression. A gene-based prognostic model was established and validated using ROC, PCA, and Kaplan-Meier analyses. A clinical-variable nomogram predicted survival, with external validation via GEO data set GSE70770. Immune traits of subtypes/risk groups were assessed via ESTIMATE, CIBERSORT, and ssGSEA. Drug sensitivity and gene expression (qRT-PCR) were evaluated. Two metabolic subtypes with distinct survival and immune patterns were identified. A four-gene signature (AKR1C2, PITPNM3, PLA2G5, UCK2) formed a prognostic model. Risk stratification revealed groups with divergent survival rates. High-risk patients exhibited poorer outcomes, reduced immune infiltration, and altered drug sensitivity. The MRG prognostic model stratifies PRAD patients by survival and immune landscape, aiding precision immunotherapy and drug discovery.

Laetiporus sulphureus, commonly known as the "sulfur polypore" or "chicken of the woods," has a global distribution and primarily grows on deciduous trees as a pathogen or saprotroph. This fungus is rich in bioactive metabolites which exhibit antimicrobial, antioxidant, and possible anticancer properties. However, its effects on hepatocarcinoma cell lines remain poorly investigated. This study evaluates the cytotoxic, antiproliferative, and antimigratory effects of L. sulphureus ethanolic extract on HepG2 and Huh7 hepatocarcinoma cell lines. The results indicate that L. sulphureus ethanolic extract significantly reduces the viability of HepG2 and Huh7 cells in a time- and dose-dependent manner and diminished colony formation. Experiments identified 15 μg/mL as the working concentration for both cell lines, as it approximated the IC50 while ensuring low toxicity. Western blot analysis reveals that L. sulphureus extract increases the expression of key tumor suppressor proteins (p53, p21, and p27), downregulates the anti-apoptotic protein Bcl-2, and upregulates the pro-apoptotic markers (Bax, cleaved caspase-9 and caspase-3), confirming apoptosis induction. Furthermore, the extract impairs Huh7 cell migration, a key factor in cancer progression, as confirmed by a reduction in Twist protein levels and an increase in E-cadherin expression. These results highlight the potential of L. sulphureus as a promising natural adjuvant for hepatocarcinoma therapy while warranting further investigation into its bioactive components, molecular mechanisms, and clinical applications.

In recent years, research on the therapeutic potential of mushroom species has notably expanded, and the effects of these organisms on cancer treatment have come to the forefront. The present review examines the anticancer and antitumor effects of various edible and medicinal mushroom species on different human cancer cell lines and summarizes the biological mechanisms underlying these effects. The reviewed studies show that polysaccharides (particularly β-glucans), triterpenoids, phenolic compounds, protein-polysaccharide complexes and other bioactive components contained in mushrooms are effective on apoptosis induction, cell cycle arrest, activation of the immune system, reduction of oxidative stress, inhibition of metastasis and angiogenesis. In vitro and in vivo studies, especially on species such as Ganoderma lucidum, Cordyceps militaris, Lentinula edodes, Hericium erinaceus, and Grifola frondosa, have shown that these mushrooms exhibit significant cytotoxic, antiproliferative, and immunomodulatory effects against various types of cancer (including breast, colon, lung, liver, prostate, cervical, etc.). These findings indicate that mushroom-derived natural products should be evaluated not only as adjunctive therapies, but also as potential pharmaceutical agents. However, most of the available data are at the preclinical level, and more comprehensive toxicological and pharmacokinetic studies are needed to ensure clinical applicability.

This study aims to compare the efficacy of magnetic nanoparticle hyperthermia for treating cancerous tissues in two distinct scenarios: breast and muscle/prostate tumors. Heat transfer dynamics during magnetic hyperthermia cancer therapy are explored using intravenously administered nanoparticles to a muscle/prostate tumor and intratumoral injection into a breast tumor. Utilizing non-Newtonian blood rheological models, we analyze a complex geometric domain for both tumor types and apply the mixed finite element technique for solving the governing equations. The impact of varying magnetic field frequencies and injected nanoparticle concentrations on heat transfer and nanoparticle transport within muscle/prostate, and breast tissues are examined numerically. Higher magnetic field frequencies and injected nanoparticle concentrations were found to increase localized heating in tumor regions, reduce therapy duration, and maximize thermal damage to cancer cells for both tumor configurations. This research provides valuable insights for optimizing magnetic hyperthermia parameters for different tumor types and also highlights the potential for personalized treatment strategies.

Nanomedicine has revolutionized the pharmaceutical and biological sciences industry by providing new frontiers and targets on the diagnosis and treatment of diseases. One promising development is the integration of natural products with nanoformulations, is emerging as a novel strategy in antitumor therapy. This combination has opened up new avenues for primary intervention and treatment due to targeted delivery of therapeutic agents against cancer. Researchers are trying to enhance and establish the safety and efficacy of naturally occurring bioactive compounds characterised by their anticancer potential. Polyphenols and other phytochemicals, along with functional foods, have high potency in circumventing tumors by the effective inhibition of the expansion of cancerous cells and induction of apoptosis. Incorporation of such natural products natural products through nanotechnology is therefore meant to enhance therapeutic efficacy with an improved safety profile. The aim will be to formulate these bioactive compounds as nanoformulations to achieve higher tumor site concentration, which would result in maximum anticancer effects and perhaps reduce the possible side effects associated with conventional therapies. This calls for collaboration among researchers and clinicians in establishing evidence-based guidelines and standardized protocols that ensure safety and efficacy in the use of such therapies.

Neurofibromatosis (NF) is a genetic condition resulting in tumor formation around neural structures, including peripheral nerves, spinal cord, and brain. Patients afflicted with NF can develop a constellation of symptoms ranging from cutaneous findings to sensory deficits and pain. When pain occurs, it could be associated with compression of neural structures or development of neuropathy itself.

A 60-year-old woman with a history of NF Type 1 (NF1) presented to our clinic for evaluation of left arm pain. Despite several neuropathic medications and surgical procedures, she continues to have neuropathic arm pain associated with neurofibromas in her brachial plexus. Further surgery was advised against by her surgeons, and she underwent a supraclavicular nerve block with us, with sustained relief of her pain.

Here, we present a patient diagnosed with NF1 and neuropathic pain due to an inoperable brachial plexus neurofibroma burden in the left axilla, successfully managed by supraclavicular nerve blocks.

CNS involvement (CNSi) of chronic lymphocytic leukemia (CLL) is a rare condition with no consensus on diagnosis and limited evidence for management and outcome. Here we report an international, multicenter, retrospective study conducted by the European Research Initiative on CLL (ERIC). The study defined CNSi of CLL by: 1) detection of CLL cells in the cerebrospinal fluid or confirmation of CLL infiltration of the CNS based on a tissue biopsy, 2) clinical or radiographic evidence of neurologic disease, and 3) the absence of other explanations for the neurologic findings. A total of 48 patients from 26 centers in 15 countries met all three diagnostic criteria of CLL-CNSi. Median age at diagnosis of CNSi was 64 years. Most patients were males (73%), had Binet stage A at CLL diagnosis (61%), and had untreated CLL at the time of CNSi (63%). Motor impairment was the most common symptom (38%) followed by visual impairment (32%). Of 47 patients who received treatment for CNSi, half (51%) received targeted agents, most commonly a BTK inhibitor (BTKi), and 34% received chemoimmunotherapy (CIT). Initial treatment was highly effective, leading to a reduction (83%) or complete resolution (71%) of neurologic symptoms and imaging findings in most patients. The estimated 5-year overall survival (OS) from the CNSi diagnosis was 77.1%. 5-year time-to-next-treatment or death was 94% for patients treated with BTKis compared to 64% for those treated with CIT. Treatment-sensitive disease, represented by attainment of CNS complete response after initial therapy, was associated with longer OS.

The development of lipid nanoparticle (LNP) systems has largely advanced RNA therapeutics, particularly mRNA-based cancer immunotherapy. Conventional amine-LNPs, designed for hepatic RNA delivery, face challenges in targeting lymphoid organs effectively and maximize antigen presentation. In this study, we present the development of pH-responsive ionizable guanidine-LNPs (G-LNPs). Our cholesterol-free G-LNP system enables efficient delivery of mRNA to the spleen following intravenous administration. Notably, while both amine-LNPs and G-LNPs can deliver mRNA to the spleen, G-LNPs exhibit a unique ability to preferentially target antigen-presenting cells, leading to significantly enhanced antigen presentation and robust T cell activation. mRNA vaccines formulated with G-LNPs elicited strong and antigen-specific immune responses, providing complete protection against tumor progression. In addition, intraperitoneal administration of G-LNPs enabled selective mRNA expression in the pancreas, showcasing the versatility of this delivery platform. These findings underscore the potential of guanidine-LNPs as a highly promising platform for organ-targeted mRNA delivery and cancer immunotherapy.

BackgroundThe CD155-TIGIT axis, a breast cancer progression biomarker, underscored neoadjuvant chemotherapy (NAC) response variability in triple-negative breast cancer (TNBC), urging biomarker-based patient stratification for timely therapy.MethodsThirty-nine TNBC patients who received NAC were recruited. The expression of TIGIT, CD155, CD226, and CD96 on tumoral and stromal cells in the tumor microenvironment was detected by immunohistochemistry, and their relationships with NAC response were explored.Results10.3% patients exhibited grade 1 (G1) response to NAC, and 20.5% achieved a complete pathological response. Notably, CD155 and CD96 were predominantly detected on tumor cells, whereas CD226 and TIGIT were predominantly detected on stromal cells. The expression of these markers did not significantly correlate with response to NAC (p > 0.05), and each individual marker lacked predictive power for determining NAC therapeutic efficacy (p > 0.05). However, a specific combination of tumoral cells expression of CD226(≥4%), CD155(≥40%), and CD96(≥35%), coupled with TIGIT expression on tumoral (<35%) and stromal cells (<12.5%), was able to identify patients with G1 response to NAC.ConclusionExpression levels of TIGIT/CD155/CD226/CD96 on tumoral and stromal cells might collectively serve as predictive biomarkers for NAC response in TNBC. This implied that CD155-TIGIT axis could be prospectively applied clinically to identify NAC-resistant TNBC patients.

While clinical RCTs have clearly evidenced that the use of androgen receptor pathway inhibitor (ARPI)s for patients with advanced prostate cancer, can significantly delay disease progression, there is insufficient evidence on their safety profiles to warrant their unqualified implementation as the treatment of choice or with which to choose between them. We aim to provide more substantial evidence for adverse event (AE)s of ARPI by analyzing real-world data (RWD) to select optimal ARPI for individual treatment.

We used data from the Food and Drug Administration Adverse Event Reporting System (FAERS) in the US, between April 30, 2014 and April 30, 2024.

We estimated proportional risk ratio (PRR)s of AEs in the US. We also compared the likelihood of AEs by age, reporter type, and ARPI groups: 1) Group 1, Enzalutamide with other medications; 2) Group 2, Apalutamide with other medications; 3) Group 3, Darolutamide with other medications; 4) Group 4, Abiraterone with other medications; 5) Group 5, Abiraterone + Enzalutamide with other medications. We identified 107,582 AEs among 44,856 US residents who were treated with ARPIs for prostate cancer. By ARPI groups, the AE of GI was the highest in Group 1 and Group 3, and the AE of vascular was the highest in Group 4 and Group 5. In particular, Group 2 showed very statistically significantly higher levels of PRR 3.558 (95%CI: 3.489-3.627) of skin-related AE compared to other groups.

Our study provides important insight that we analyzed RWD and evaluated comparative drug safety across all type of prostate cancer. Although we could not make a conclusion whether which is the safest ARPI, we can suggest that each ARPIs have different types of AEs hence we can use this information during choosing ARPIs for prostate cancer patients.