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Background: The aim of the present study is to evaluate the impact of metastases-directed stereotactic body radiotherapy in two groups of oligometastatic prostate cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant PC (oligo-CRPC). Methods: Inclusion criteria of the present multicentre retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1–3 lesions (bone or nodes) detected with choline positron emission tomography or CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as metastases (bone or nodes) detected after a prostatic-specific antigen rise during androgen deprivation therapy (ADT). Primary end points were: distant progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC patients. Results: About 100 patients with oligorecurrent PC (139 lesions) and 41 with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1- and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were 43.2 and 21.6%. Limitations include the retrospective design. Conclusions: Stereotactic body radiotherapy seems to be a useful treatment both for oligorecurrent and oligo-CRPC.

In vitro chondrocyte expansion is key to all tissue engineering (TE) strategies using adult differentiated articular chondrocytes. Unfortunately, high proliferation rates in vitro can cause a progressive loss of chondrocyte phenotype (dedifferentiation) during culture passages. This can impair the quality of newly formed tissue after implantation because dedifferentiated chondrocytes mainly produce fibrocartilage, which hinders successful cartilage repair. Freshly isolated chondrocytes from equine articular cartilage were grown as a primary culture on tissue culture dishes and on 2D chitosan or chitosan/hyaluronic acid films. To evaluate chondrocyte differentiation during in vitro expansion, morphological observations, gene expression of chondrocyte phenotype markers, and LC-MS/MS shotgun proteomics were performed. All types of 2D cultures showed significantly reduced differentiation compared with freshly isolated cells, but chondrocytes grown on biomaterials maintained a rounded morphology and the gene expression of differentiation markers. Interestingly, pairwise proteomics comparison revealed a remarkable number of differentially expressed proteins, highlighting the different dynamics occurring in each experimental condition at the protein level. Based on novel insights into differentiation-dedifferentiation mechanisms, hypotheses were generated to explore new markers implicated in dedifferentiation and the role of biomaterials in this process by investigating the biological pathways associated with the reduced phenotype.

Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized by increased expression and activity of mechanisms promoting survival, proliferation, and metastatic spread. The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called “cancer stem cells”. Mebendazole meets many of the characteristics desirable for a repurposed drug: good and proven toxicity profile, pharmacokinetics allowing to reach therapeutic concentrations at disease site, ease of administration and low price. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response. In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival. Further investigations are warranted to confirm the clinical anti-neoplastic activity of MBZ and its safety in combination with other drugs in a clinical setting.

Background Gut microbial anaerobic fermentation produces short-chain fatty acids (SCFA), which are important substrates for energy metabolism and anabolic processes in mammals. SCFA can regulate the inflammatory response and increase the intestinal barrier integrity by enhancing the tight junction protein (TJp) functions, which prevent the passage of antigens through the paracellular space. The aim of this study was to evaluate the effect of in vitro supplementation with SCFA (acetate, propionate, butyrate, and lactate) at different concentrations on viability, nitric oxide (NO) release (oxidative stress parameter) in cell culture supernatants, and gene expression of TJp (occludin, zonula occludens-1, and claudin-4) and pro-inflammatory pathway-related mediators (β-defensin 1, TNF-α, and NF-κB) in intestinal porcine epithelial cell line J2 (IPEC-J2). Results The SCFA tested showed significant effects on IPEC-J2, which proved to be dependent on the type and specific concentration of the fatty acid. Acetate stimulated cell viability and NO production in a dose-dependent manner (P < 0.05), and specifically, 5 mM acetate activated the barrier response through claudin-4, and immunity through β-defensin 1 (P < 0.05). The same effect on these parameters was shown by propionate supplementation, especially at 1 mM (P < 0.05). Contrarily, lactate and butyrate showed different effects compared to acetate and propionate, as they did not stimulate an increase of cell viability and regulated barrier integrity through zonula occludens-1 and occludin, especially at 30 mM and 0.5 mM, respectively (P < 0.05). Upon supplementation with SCFA, the increase of NO release at low levels proved not to have detrimental effects on IPEC-J2 proliferation/survival, and in the case of acetate and propionate, such levels were associated with beneficial effects. Furthermore, the results showed that SCFA supplementation induced β-defensin 1 (P < 0.05) that, in turn, may have been involved in the inhibition of TNF-α and NF-κB gene expression (P < 0.05). Conclusions The present study demonstrates that the supplementation with specific SCFA in IPEC-J2 can significantly modulate the process of barrier protection, and that particularly acetate and propionate sustain cell viability, low oxidative stress activity and intestinal barrier function.

Treatments given to cancer patients can cause negative side effects. For example, a treatment known as androgen deprivation therapy – which is used to reduce male sex hormone levels in prostate cancer patients – can lead to increased body fat percentage and decreased bone density. These adverse effects can have further negative impacts on patient health, such as increasing the risk of cardiovascular disease and fractures from falls from standing height or less, respectively. Understanding how androgen deprivation therapy contributes to these negative side effects may help clinicians better manage care and outcomes for patients with prostate cancer. Follicle stimulating hormone (or FSH for short) has roles in male and female reproduction but has also been linked to changes in body composition. For example, elevated FSH levels are associated with higher total fat body mass in post-menopausal women. While androgen deprivation therapy is known to alter FSH blood levels, the impact of this change in prostate cancer patients was not well understood. To investigate the effect of androgen deprivation therapy on FSH levels and body composition, Bergamini et al. used X-ray technology to measure total fat body mass in prostate cancer patients before and after undergoing 12 months of androgen deprivation therapy. The findings showed that patient FSH blood levels significantly decreased after 12 months of treatment. Higher FSH blood levels strongly correlated with increased total fat body mass after 12 months of treatment. The findings of this clinical trial suggest that FSH blood levels impact the body composition of patients undergoing androgen deprivation therapy. As a result, FSH blood levels may be a suitable biomarker for identifying patients that are more likely to develop obesity and are therefore at greater risk of complications such as cardiovascular disease.

PurposeHerein, we report the clinical outcomes of a multicenter study evaluating the role of SBRT in a cohort of patients affected by oligoprogressive castration-resistant prostate cancer (CRPC).Materials and methodsThis is a retrospective multicenter observational study including eleven centers. Inclusion criteria of the current study were: (a) Karnofsky performance status > 80, (b) histologically proven diagnosis of PC, (c) 1–5 oligoprogressive metastases, defined as progressive disease at bone or nodes levels (detected by means of choline PET/CT or CT plus bone scan) during ADT, (d) serum testosterone level under 50 ng/ml during ADT, (e) controlled primary tumor, (f) patients treated with SBRT with a dose of at least 5 Gy per fraction to a biologically effective dose (BED) of at least 80 Gy using an alpha-to-beta ratio of 3 Gy, (g) at least 6 months of follow-up post-SBRT.ResultsEighty-six patients for a total of 117 lesions were treated with SBRT. The median follow-up was 30.7 months (range 4–91 months). The median new metastasis-free survival after SBRT was 12.3 months (95% CI 5.5–19.1 months). One- and two-year distant progression-free survival was 52.3% and 33.7%, respectively. Twenty-six out of 86 patients underwent a second course of SBRT due to further oligoprogressive disease: This resulted in a median systemic treatment-free survival of 21.8 months (95% CI 17.8–25.8 months). One-year systemic treatment-free survival was 72.1%.ConclusionSBRT appears to be a promising approach in oligoprogressive castration-resistant prostate cancer. Further investigations are warranted.

Introduction Historically, the management of relapsed or refractory diffuse large B-cell lymphoma (r/r-DLBCL) involved chemotherapy and autologous stem cell transplant, though outcomes were often suboptimal. Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the therapeutic landscape for r/r-DLBCL, achieving high response rates and improving progression-free and overall survival. However, a significant proportion of patients relapse after CAR-T, and optimal treatment strategies for post-CAR-T relapse remain unclear. Radiotherapy (RT), a highly effective treatment for lymphoma, is increasingly recognized for its potential role as both a bridging therapy and a salvage option following CAR-T relapse. Methods A comprehensive literature review was conducted using databases including PubMed, Scopus, EMBASE, and Cochrane Library, with search terms combining “radiotherapy,” “radiation therapy,” “lymphoma,” and “CAR T-cell.” A total of 690 records were screened, and 14 studies were included in the analysis after applying inclusion and exclusion criteria. Results RT demonstrates high response rates in CAR-T relapsed DLBCL, with overall response rates (ORR) ranging from 35% to 82.4% and complete response rates (CRR) from 17% to 59%. One-year local control rates ranged between 62% and 84%. Salvage RT showed comparable or superior outcomes to systemic therapies in multiple studies, particularly in patients with localized relapses. The toxicity profile of RT was favorable, particularly when modern techniques such as IMRT were employed. Case reports and retrospective series highlighted its effectiveness in achieving durable responses and controlling localized disease progression. Conclusions Radiotherapy is a safe and effective treatment option for patients with DLBCL relapsed or refractory after CAR-T therapy. It achieves high local control rates and favorable outcomes, particularly in patients with localized relapse. Incorporating RT into the therapeutic workflow may enhance the management of this challenging population. Further prospective studies are needed to define its role and optimize treatment sequencing.

Canine cognitive dysfunction (CCD) is a common age-related neurodegenerative disorder in dogs that shares several pathological and clinical features with human Alzheimer’s disease (AD). In both species, β-amyloid (Aβ) accumulates within the brain parenchyma and cerebral vessel walls and is associated with synaptic loss, oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation, ultimately leading to progressive cognitive decline. Increasing evidence indicates that impairment of brain clearance mechanisms, particularly the glymphatic system, represents a central pathogenic mechanism in both CCD and AD. The glymphatic system is a glia-dependent perivascular network involved in the clearance of Aβ and other metabolic waste products from the brain. Its function declines with aging, vascular disease, and astrocytic alterations, including changes in aquaporin-4 distribution. Reduced glymphatic and periarterial drainage promotes the retention and aggregation of Aβ and tau proteins. Compared with AD, tau pathology in CCD is generally less extensive, supporting the interpretation of CCD as an Aβ-predominant condition and a partial pathological analog of Alzheimer’s disease. Clinically, CCD is characterized by a constellation of behavioral changes including, disorientation, altered social interactions, sleep–wake cycle disturbances, a loss of housetraining, changes in activity levels, and increased anxiety, commonly summarized by the DISHAA acronym. Overall, CCD represents a valuable spontaneous large-animal model for investigating neurodegenerative mechanisms and clearance-related therapeutic targets relevant to both veterinary and human medicine.

Introduction: Stereotactic radiotherapy (SRT) is increasingly used in oligometastatic non-small-cell lung cancer (NSCLC) and is known to elicit systemic immune effects, although the underlying mechanisms remain not fully understood. Methods: In this prospective pilot study, we evaluated plasma cytokine variations in 19 patients with oligometastatic or oligoprogressive NSCLC undergoing SRT. Peripheral blood samples were collected before treatment (T0) and one month after SRT (T1) and the concentrations of nine cytokines (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A and TNF-α) were quantified using a multiplex Luminex assay. Non-parametric tests and Cox regression models were used to investigate associations between cytokine levels, clinical variables, systemic treatments, and survival outcomes. SRT induced significant post-treatment increases in IFN-γ, IL-2, and IL-6, consistent with systemic pro-inflammatory activation and T-cell stimulation. Cytokine dynamics were influenced by patient- and tumor-related factors: female sex was associated with higher IL-2 and TNF-α levels; oncogene-addicted tumors showed lower IL-6 levels; and oligoprogressive disease exhibited attenuated cytokine variations compared with metachronous oligometastatic disease. Tyrosine kinase inhibitors were associated with globally reduced cytokine levels and blunted IL-1/IL-2 changes, whereas patients receiving immune checkpoint inhibitors displayed higher IL-2 and IL-6 concentrations and greater post-SRT increases in IFN-γ. Oncogene-addicted status and IL-12 variation emerged as independent predictors of overall survival and a composite model integrating these variables significantly stratified prognosis. Conclusions: These findings suggest that SRT triggers measurable systemic immune activation in oligometastatic NSCLC, which is further shaped by tumor biology, disease burden, and concomitant systemic therapies. Although limited by the small sample size, this study supports the feasibility and potential utility of cytokine profiling to refine patient selection and guide biomarker-driven combinations of SRT with targeted and immune-based treatments, warranting validation in larger prospective cohorts.

PurposeNew RT techniques and data emerging from follow-up for several tumor sites suggest that treatment volume de-escalation may permit to minimize therapy-related side effects and/or obtain better clinical outcomes. Here, we summarize the main evidence about volume de-escalation in RT.MethodThe relevant literature from PubMed was reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic.ResultsIn Lymphoma, large-volume techniques (extended- and involved-field RT) are being successfully replaced by involved-site RT and involved-node RT. In head and neck carcinoma, spare a part of elective neck is controversial. In early breast cancer, partial breast irradiation has been established as a treatment option in low-risk patients. In pancreatic cancer stereotactic body radiotherapy may be used to dose escalation. Stereotactic radiosurgery should be the treatment choice for patients with oligometastatic brain disease and a life expectancy of more than 3 months, and it should be considered an alternative to WBRT for patients with multiple brain metastases.ConclusionFurther clinical trials are necessary to improve the identification of suitable patient cohorts and the extent of possible volume de-escalation that does not compromise tumor control.