Search Results (65)

Multidrug-resistant (MDR) bacterial infections present a major challenge in cancer therapy, particularly for immunocompromised patients undergoing chemotherapy, radiation, or surgery. These infections often arise from prolonged antibiotic use, hospital-acquired pathogens, and weakened immune defenses, leading to increased morbidity and mortality. As conventional antibiotics become less effective against MDR strains, there is an urgent need for alternative treatment options. This review highlights phage therapy as a promising approach to managing MDR bacterial infections in cancer patients. Once widely used, phage therapy has recently regained attention as a targeted antimicrobial strategy that can specifically eliminate harmful bacteria while preserving the beneficial microbiota. Phages work by directly lysing bacteria, disrupting biofilms, and synergizing with antibiotics to restore bacterial susceptibility. These mechanisms make phage therapy especially appealing for treating infections that complicate cancer treatments. However, the clinical application of phage therapy faces challenges such as variability in phage–host interactions, regulatory hurdles, and immune responses in patients. This review identifies gaps in current research regarding the use of phage therapy for MDR infections in cancer patients. By examining recent innovations, therapeutic mechanisms, and associated limitations, we provide valuable insights into the potential of phage therapy for improving infection management in oncology. Future research should focus on refining phage delivery methods, assessing long-term safety, and exploring combination therapies to maximize clinical efficacy. Overcoming these challenges could position phage therapy as a valuable complement to existing antimicrobial strategies in cancer care. Full article

The in situ and label-free detection of molecular information in biological cells has always been a challenging problem due to the weak Raman signal of biological molecules. The use of various resonance nanostructures has significantly advanced Surface-enhanced Raman spectroscopy (SERS) in signal enhancement in recent years. However, biological cells are often immersed in different formulations of culture medium with varying refractive indexes and are highly sensitive to the temperature of the microenvironment. This necessitates that SERS meets the requirements of refractive index insensitivity, low thermal damage, broadband enhancement, and other needs in addition to signal enhancement. Here, we propose a SERS chip with integrated dual Fano resonance and the corresponding analytical model. This model can be used to quickly lock the parameters and then analyze the performance of the dual resonance SERS chip. The simulation and experimental characterization results demonstrate that the integrated dual Fano resonances have the ability for independent broadband tuning. This capability enhances both the excitation and radiation processes of Raman signals simultaneously, ensuring that the resonance at the excitation wavelength is not affected by the culture medium (the refractive index) and reduces heat generation. Furthermore, the dual Fano resonance modes can synergize with each other to greatly enhance both the amplitude and enhanced range of the Raman signal, providing a stable, reliable, and comprehensive detection tool and strategy for fingerprint signal detection of bioactive samples. Full article

Background/Objectives: Peroxisome proliferator–activated receptor γ (PPARγ) plays a key role in mediating anti-inflammatory and anticancer effects in the tumor microenvironment. Kaurenoic acid (KA), a diterpene compound isolated from Sphagneticola trilobata (L.) Pruski, has been demonstrated to exert anti-inflammatory, anticancer, and antihuman immunodeficiency virus effects. Methods: In this study, we identified KA as a novel activator of PPARγ with potent anti-inflammatory and antitumor effects both in vitro and in vivo. Given the potential of PPARγ regulators in overcoming radioresistance and chemoresistance in cancer therapies, we hypothesized that KA may enhance the efficacy of breast cancer radiotherapy. Results: In a lipopolysaccharide (LPS)-induced mouse inflammation model, KA treatment reduced the levels of pro-inflammatory cytokines, including COX-2, IL-6, IL-1β, and TNFα. In a xenograft mouse mode of breast cancer, KA treatment inhibited tumor growth. Specifically, KA treatment enhanced caspase-3 activity and cytotoxicity against MDA-MB-231 and MCF-7 breast cancer cells. When KA was co-treated with a caspase inhibitor, Z-VAD-FMK, caspase-dependent apoptosis was suppressed in these cells. KA was found to induce the generation of cytosolic calcium ions (Ca²⁺) and reactive oxygen species (ROS), triggering endoplasmic reticulum (ER) stress via the PERK-ATF4-CHOP axis. Hence, the ER stressor thapsigargin (TG) synergized with KA treatment to enhance apoptosis in these cells, while the loss of the PERK or CHOP function inhibited this phenomenon. KA treatment was shown to induce oxidative stress via the NADPH oxidase 4 (NOX4) and stimulate ROS production. Specifically, NOX4 knockdown (KD) and antioxidant treatment (N-acetyl cysteine or diphenyleneiodonium) suppressed such ER stress–mediated apoptosis by inhibiting KA-enhanced caspase-3 activity, cytotoxicity, and intracellular ROS production in the treated cells. In radioresistant MDA-MB-231R and MCF-7R cells, KA combined with 2 Gy radiation overcame radioresistance by upregulating PPARγ and modulating epithelial–mesenchymal transition (EMT) markers, such as E-cadherin, N-cadherin, and vimentin. In PPARγ KD MDA-MB-231R and MCF-7R cells, this phenomenon was inhibited due to reduced PPARγ and NOX4 expression. Conclusions: In conclusion, these findings demonstrated KA as a novel PPARγ regulator with promising potential to enhance the efficacy of breast cancer radiotherapy. Full article

Background: Antibiotics remain the most effective option for combating infections. However, the situation has shifted from ideal to concerning, as bacterial resistance to antibiotics is increasing in both prevalence and strength. Objectives: This study explores the synergistic/antagonistic potential of combining antibiotic and photodynamic therapy (PDT) against Pseudomonas aeruginosa. Methods: We conducted in vitro experiments to observe the effect of the sequential application of antibiotics and photodynamic therapy with a time interval between them. The antibiotics used were ciprofloxacin, ceftriaxone, and gentamicin, and Photodithazine was employed as the photosensitizer, with the PDT performed at different light doses of 660 nm radiation. Results: The combined effect was highly dependent on the antibiotic. While for gentamicin, the combination of antibiotic and PDT treatment was always synergistic, for ciprofloxacin, it could be severely antagonistic. Each antibiotic exhibited a distinctive pattern of interaction with PDT. Gentamicin resulted in the largest enhancement in bactericidal activity combined with PDT, requiring lower antibiotic concentrations to achieve significant bacterial reduction. Ceftriaxone’s bactericidal action was less influenced by PDT intensity, maintaining a stable efficacy regardless of different PDT dosages. Conversely, the outcome of ciprofloxacin was highly dependent on the antibiotic concentration changing from synergic to antagonistic action. Conclusions: The findings advocate for the development of treatment protocols that combine antibiotics and PDT and necessitate the establishment of the criterion for the dosage and periodicity of administration of such combination protocols. The demonstrated results open the doors wide to new applications and opportunities to combat infectious diseases through the combined use of photodynamic therapy and antibiotics. Full article

Epigenetic dysregulation has long been recognized as a significant contributor to tumorigenesis and tumor maintenance, impacting all recognized cancer hallmarks. Although some epigenetic drugs have received regulatory approval for certain hematological malignancies, their efficacy in treating solid tumors has so far been largely disappointing. However, recent advancements in developing new compounds and a deeper understanding of cancer biology have led to success in specific solid tumor subtypes through precision medicine approaches. Moreover, epigenetic drugs may play a crucial role in synergizing with other anticancer treatments, enhancing the sensitivity of cancer cells to various anticancer therapies, including chemotherapy, radiation therapy, hormone therapy, targeted therapy, and immunotherapy. In this review, we critically evaluate the evolution of epigenetic drugs, tracing their development from initial use as monotherapies to their current application in combination therapies. We explore the preclinical rationale, completed clinical studies, and ongoing clinical trials. Finally, we discuss trial design strategies and drug scheduling to optimize the development of possible combination therapies. Full article

In the last decades, breakthrough advances in understanding the mechanisms of the Universe and fundamental physics have been achieved through the exploitation of data on cosmic rays and high-energy radiation gathered via orbiting experiments, in a synergic and complementary international effort that combines space-based instrument data with ground-based space observatories, accelerator, and collider experiments [...] Full article

PANDORA (Plasmas for Astrophysics Nuclear Decays Observation and Radiation for Archaeometry) is an INFN project aiming at measuring, for the first time, possible variations in in-plasma $\beta$-decay lifetimes in isotopes of astrophysical interest as a function of thermodynamical conditions of the in-laboratory controlled plasma environment. Theoretical predictions indicate that the ionization state can dramatically modify the $\beta$-decay lifetime (even of several orders of magnitude). The PANDORA experimental approach consists of confining a plasma able to mimic specific stellar-like conditions and measuring the nuclear decay lifetime as a function of plasma parameters. The $\beta$-decay events will be measured by detecting the $\gamma$-ray emitted by the daughter nuclei, using an array of 12 HPGe detectors placed around the magnetic trap. In this frame, plasma parameters have to be continuously monitored online. For this purpose, an innovative, non-invasive multi-diagnostic system, including high-resolution time- and space-resolved X-ray analysis, was developed, which will work synergically with the $\gamma$-rays detection system. In this contribution, we will describe this multi-diagnostics system with a focus on spatially resolved high-resolution X-ray spectroscopy. The latter is performed by a pin-hole X-ray camera setup operating in the 0.5–20 keV energy domain. The achieved spatial and energy resolutions are 450 µm and 230 eV at 8.1 keV, respectively. An analysis algorithm was specifically developed to obtain SPhC (Single Photon-Counted) images and local plasma emission spectrum in High-Dynamic-Range (HDR) mode. Thus, investigations of image regions where the emissivity can change by even orders of magnitude are now possible. Post-processing analysis is also able to remove readout noise, which is often observable and dominant at very low exposure times (ms). Several measurements have already been used in compact magnetic plasma traps, e.g., the ATOMKI ECRIS in Debrecen and the Flexible Plasma Trap at LNS. The main outcomes will be shortly presented. The collected data allowed for a quantitative and absolute evaluation of local emissivity, the elemental analysis, and the local evaluation of plasma density and temperature. This paper also discusses the new plasma emission models, implemented on PIC-ParticleInCell codes, which were developed to obtain powerful 3D maps of the X-rays emitted by the magnetically confined plasma. These data also support the evaluation procedure of spatially resolved plasma parameters from the experimental spectra as well as, in the near future, the development of appropriate algorithms for the tomographic reconstruction of plasma parameters in the X-ray domain. The described setups also include the most recent upgrade, consisting of the use of fast X-ray shutters with special triggering systems that will be routinely implemented to perform both space- and time-resolved spectroscopy during transient, stable, and turbulent plasma regimes (in the ms timescale). Full article

The inheritance of historic human-induced disruption and the fierceness of its impact change aquatic ecosystems. This work reviews some of the main stressors on freshwater ecosystems, focusing on their effects, threats, risks, protection, conservation, and management elements. An overview is provided on the water protection linked to freshwater stressors: solar ultraviolet radiation, thermal pollution, nanoparticles, radioactive pollution, salinization, nutrients, sedimentation, drought, extreme floods, fragmentation, pesticides, war and terrorism, algal blooms, invasive aquatic plants, riparian vegetation, and invasive aquatic fish. Altogether, these stressors build an exceptionally composite background of stressors that are continuously changing freshwater ecosystems and diminishing or even destroying their capability to create and maintain ongoing natural healthy products and essential services to humans. Environmental and human civilization sustainability cannot exist without the proper management of freshwater ecosystems all over the planet; this specific management is impossible if the widespread studied stressors are not deeply understood structurally and functionally. Without considering each of these stressors and their synergisms, the Earth’s freshwater is doomed in terms of both quantitative and qualitative aspects. Full article

Ablative composites serve as sacrificial materials, protecting underlying materials from high-temperature environments by endothermic reactions. These materials undergo various phenomena, including thermal degradation, pyrolysis, gas generation, char formation, erosion, gas flow, and different modes of heat transfer (such as conduction, convection, and radiation), all stemming from these endothermic reactions. These phenomena synergize to form a protective layer over the underlying materials. Carbon, with its superb mechanical properties and various available forms, is highlighted, alongside phenolics known for good adhesion and fabric ability and elastomers valued for flexibility and resilience. This study focuses on recent advancements in carbon-and-phenolic and carbon-and-elastomeric composites, considering factors such as erosion speed; high-temperature resistance; tensile, bending, and compressive strength; fiber–matrix interaction; and char formation. Various authors’ calculations regarding the percentage reduction in linear ablation rate (LAR) and mass ablation rate (MAR) are discussed. These analyses inform potential advancements in the field of carbon/phenolic and carbon/elastomeric ablative composites. Full article

Background and purpose. Chimeric antigen receptor (CAR) T cells have been relatively ineffective against solid tumors. Low-dose radiation which can be delivered to multiple sites of metastases by targeted radionuclide therapy (TRT) can elicit immunostimulatory effects. However, TRT has never been combined with CAR T cells against solid tumors in a clinical setting. This study investigated the effects of radiation delivered by Lutetium-177 (¹⁷⁷Lu) and Actinium-225 (²²⁵Ac) on the viability and effector function of CAR T cells in vitro to evaluate the feasibility of such therapeutic combinations. After the irradiation of anti-GD2 CAR T cells with various doses of radiation delivered by ¹⁷⁷Lu or ²²⁵Ac, their viability and cytotoxic activity against GD2-expressing human CHLA-20 neuroblastoma and melanoma M21 cells were determined by flow cytometry. The expression of the exhaustion marker PD-1, activation marker CD69 and the activating receptor NKG2D was measured on the irradiated anti-GD2 CAR T cells. Both ¹⁷⁷Lu and ²²⁵Ac displayed a dose-dependent toxicity on anti-GD2 CAR T cells. However, radiation enhanced the cytotoxic activity of these CAR T cells against CHLA-20 and M21 irrespective of the dose tested and the type of radionuclide. No significant changes in the expression of PD-1, CD69 and NKG2D was noted on the CAR T cells following irradiation. Given a lower CAR T cell viability at equal doses and an enhancement of cytotoxic activity irrespective of the radionuclide type, ¹⁷⁷Lu-based TRT may be preferred over ²²⁵Ac-based TRT when evaluating a potential synergism between these therapies in vivo against solid tumors. Full article

Radiotherapy and/or chemotherapy have been used for nearly 100 years to treat lymphoma. Recently, immunotherapy has been incorporated into the treatment of lymphomas. Here, we will review both the role of immunotherapy in lymphoma as well as the feasibility of incorporating immunotherapies with conventional lymphoma treatments, especially radiotherapy. Immunotherapy agents include checkpoint inhibitors that target the PD-1/PD-L1 axis, CTLA-4, or CD47. In addition, other immunotherapy agents such as bi-specific antibodies and CD19 CAR-T cell therapy are being implemented in various non-Hodgkin’s lymphomas. Extrapolating from observations in other disease sites and incorporating immunotherapy with conventional treatments of lymphoma, including radiotherapy, may have opposing effects. Radiotherapy may stimulate anti-tumor immune responses that synergize with immunotherapies. In contrast, radiotherapy, as well as chemotherapy, may also induce local and systemic immune dysfunction which reduces the efficacy of immunotherapies. With newer radiation treatment techniques and limited radiation fields, it is likely that the efficacy of immunotherapy can be maintained when included with conventional treatments. Therefore, there remains an unmet need to better understand the role of immunotherapy alone and in combination with current treatments in lymphoma patients. Full article

[¹⁸F]-FDG positron emission tomography with computed tomography (PET/CT) imaging is widely used to enhance the quality of care in patients diagnosed with cancer. Furthermore, it holds the potential to offer insight into the synergic effect of combining radiation therapy (RT) with immuno-oncological (IO) agents. This is achieved by evaluating treatment responses both at the RT and distant tumor sites, thereby encompassing the phenomenon known as the abscopal effect. In this context, PET/CT can play an important role in establishing timelines for RT/IO administration and monitoring responses, including novel patterns such as hyperprogression, oligoprogression, and pseudoprogression, as well as immune-related adverse events. In this commentary, we explore the incremental value of PET/CT to enhance the combination of RT with IO in precision therapy for solid tumors, by offering supplementary insights to recently released joint guidelines. Full article

Radiation therapy (RT) has recently demonstrated promise at stimulating an enhanced immune response. The recent success of immunotherapies, such as checkpoint inhibitors, CART cells, and other immune modulators, affords new opportunities for combination with radiation. The aim of this study is to evaluate whether and to what extent blockade of VISTA, an immune checkpoint, can potentiate the tumor control ability of radiation therapy. Our study is novel in that it is the first comparison of two VISTA-blocking methods (antibody inhibition and genetic knockout) in combination with RT. VISTA was blocked either through genetic knockout (KO) or an inhibitory antibody and combined with RT in two syngeneic murine flank tumor models (B16 and MC38). Selected mRNA, immune cell infiltration, and tumor growth delay were used to assess the biological effects. When combined with a single 15Gy radiation dose, VISTA blockade via genetic knockout in the B16 model and via anti-VISTA antibodies in the MC38 model significantly improved survival compared to RT alone by an average of 5.5 days and 6.3 days, respectively (p < 0.05). The gene expression data suggest that the mechanism behind the enhanced tumor control is primarily a result of increased apoptosis and immune-mediated cytotoxicity. VISTA blockade significantly enhances the anti-tumor effect of a single dose of 15Gy radiation through increased expression and stimulation of cell-mediated apoptosis pathways. These results suggest that VISTA is a biologically relevant immune promoter that has the potential to enhance the efficacy of a large single radiation dose in a synergic manner. Full article

HDAC inhibitors (HDACi) hold great potential as anticancer therapies due to their ability to regulate the acetylation of both histone and non-histone proteins, which is frequently disrupted in cancer and contributes to the development and advancement of the disease. Additionally, HDACi have been shown to enhance the cytotoxic effects of DNA-damaging agents such as radiation and cisplatin. In this study, we found that histone deacetylase inhibits valproic acid (VPA), synergized with PARP1 inhibitor (PARPi), talazoparib (BMN-673), and alkylating agent, and temozolomide (TMZ) to induce DNA damage and reduce glioblastoma multiforme. At the molecular level, VPA leads to a downregulation of FANCD2 and RAD51, and the eradication of glioblastoma cells. The results of this study indicate that combining HDACi with PARPi could potentially enhance the treatment of glioblastoma, the most aggressive type of cancer that originates in the brain. Full article