Stem cells differentiate into mature organ/tissue-specific cells at a steady pace under normal conditions, but their growth can be accelerated during the process of tissue healing or in the context of certain diseases. It is postulated that the proliferation and growth of carcinomas are sustained by the presence of a vital cellular compartment resembling stem cells residing in normal tissues: ‘stem-like cancer cells’ or cancer stem cells (CSCs). Mutations in prostate stem cells can lead to the formation of prostate cancer. Prostate CSCs (PCSCs) have been identified and partially characterized. These express surface markers include CD44, CD133, integrin α2β1, and pluripotency factors like OCT4, NANOG, and SOX2. Several signaling pathways are also over-activated, including Notch, PTEN/Akt/PI3K, RAS-RAF-MEK-ERK and HH. Moreover, PCSCs appear to induce resistance to radiotherapy and chemotherapy, while their presence has been linked to aggressive cancer behavior and higher relapse rates. The development of treatment policies to target PCSCs in tumors is appealing as radiotherapy and chemotherapy, through cancer cell killing, trigger tumor repopulation via activated stem cells. Thus, blocking this reactive stem cell mobilization may facilitate a positive outcome through cytotoxic treatment.

The recent progress in Nanotechnology has introduced Gold Nanoparticles (AuNPs) as promising radiosensitizing agents in radiation oncology. This work aims to estimate dose enhancement due to the presence of AuNPs inside an irradiated water region through Monte Carlo calculations. The GATE platform was used to simulate 6 MV photon histories generated from a TrueBeam^® linear accelerator with and without a Flattening Filter (FF) and model AuNPs clusters. The AuNPs size, concentration and distribution pattern were examined. To investigate different clinical irradiation conditions, the effect of field size, presence of FF and placement of AuNPs in water were evaluated. The range of Dose Enhancement Factors (DEF = Dose_Au/Dose_Water) calculated in this study is 0.99 ± 0.01–1.26 ± 0.02 depending on photon beam quality, distance from AuNPs surface, AuNPs size and concentration and pattern of distribution. The highest DEF is reported for irradiation using un-flattened photon beams and at close distances from AuNPs. The obtained findings suggest that dose deposition could be increased in regions that represent whole cells or subcellular targets (mitochondria, cell nucleus, etc.). Nevertheless, further and consistent research is needed in order to make a step toward AuNP-aided radiotherapy in clinical practice.

Hydrogen sulfide (H₂S) has recently been recognized as a novel gaseous transmitter with several anti-inflammatory properties. The role of host- derived H₂S in infections by Pseudomonas aeruginosa was investigated in clinical and mouse models. H₂S concentrations and survival was assessed in septic patients with lung infection. Animal experiments using a model of severe systemic multidrug-resistant P. aeruginosa infection were performed using mice with a constitutive knock-out of cystathionine-γ lyase (Cse) gene (Cse^-/-) and wild-type mice with a physiological expression (Cse^+/+). Experiments were repeated in mice after a) treatment with cyclophosphamide; b) bone marrow transplantation (BMT) from a Cse^+/+ donor; c) treatment with H₂S synthesis inhibitor aminooxyacetic acid (ΑΟΑΑ) or propargylglycine (PAG) and d) H₂S donor sodium thiosulfate (STS) or GYY3147. Bacterial loads and myeloperoxidase activity were measured in tissue samples. The expression of quorum sensing genes (QS) was determined in vivo and in vitro. Cytokine concentration was measured in serum and incubated splenocytes. Patients survivors at day 28 had significantly higher serum H₂S compared to non-survivors. A cut- off point of 5.3 μΜ discriminated survivors with sensitivity 92.3%. Mortality after 28 days was 30.9% and 93.7% in patients with H₂S higher and less than 5.3 μΜ (p = 7 x 10⁻⁶). In mice expression of Cse and application of STS afforded protection against infection with multidrug-resistant P. aeruginosa. Cyclophosphamide pretreatment eliminated the survival benefit of Cse^+/+ mice, whereas BMT increased the survival of Cse^-/- mice. Cse^-/- mice had increased pathogen loads compared to Cse^+/+ mice. Phagocytic activity of leukocytes from Cse^-/- mice was reduced but was restored after H₂S supplementation. An H₂S dependent down- regulation of quorum sensing genes of P.aeruginosa could be demonstrated in vivo and in vitro. Endogenous H₂S is a potential independent parameter correlating with the outcome of P. aeruginosa. H₂S provides resistance to infection by MDR bacterial pathogens.

The surface-guided radiotherapy (SGRT) technique improves patient positioning with submillimeter accuracy compared with the conventional positioning technique of lasers using three-point tattoos. SGRT provides solutions to considerations that arise from the conventional setup technique, such as variability in tattoo position and the psychological impact of the tattoos. Moreover, SGRT provides monitoring of intrafractional motion. Purpose: This literature review covers the basics of SGRT systems and examines whether SGRT can replace the traditional positioning technique. In addition, it investigates SGRT’s potential in reducing positioning times, factors affecting SGRT accuracy, the effectiveness of live monitoring, and the impact on patient dosage. Materials and Methods: This study focused on papers published from 2016 onward that compared SGRT with the traditional positioning technique and investigated factors affecting SGRT accuracy and effectiveness. Results/Conclusions: SGRT provides the same or better results regarding patient positioning. The implementation of SGRT can reduce overall treatment time. It is an effective technique for detecting intrafraction patient motion, improving treatment accuracy and precision, and creating a safe and comfortable environment for the patient during treatment.

Background: During RT cycles, the tumor response pattern could affect tumor coverage and may lead to organs at risk of overdose. As such, early prediction of significant volumetric changes could therefore reduce potential radiation-related adverse effects. Nevertheless, effective machine learning approaches based on the radiomic features of the clinically used CBCT images to determine the tumor volume variations due to RT not having been implemented so far. Methods: CBCT images from 40 HN cancer patients were collected weekly during RT treatment. From the obtained images, the Clinical Target Volume (CTV) and Parotid Glands (PG) regions of interest were utilized to calculate 104 delta-radiomics features. These features were fed on a feature selection and classification procedure for the early prediction of significant volumetric alterations. Results: The proposed framework was able to achieve 0.90 classification performance accuracy while detecting a small subset of discriminative characteristics from the 1st week of RT. The selected features were further analyzed regarding their effects on temporal changes in anatomy and tumor response modeling. Conclusion: The use of machine learning algorithms offers promising perspectives for fast and reliable early prediction of large volumetric deviations as a result of RT treatment, exploiting hidden patterns in the overall anatomical characteristics.

Head and neck cancer (HNC) includes various malignancies and represents the seventh most common cancer worldwide. The early diagnosis of HNC results in a 70–90% five-year survival rate, which declines with locally advanced stages of disease. Current care employs a multimodal strategy encompassing surgery, radiation therapy (RT), chemotherapy, and immunotherapy, while treatment options vary according to the stage, tumor features, and patient characteristics. About 75% of patients with HNC will benefit from RT, either as a primary treatment or as adjuvant therapy following surgical resection. Technological improvements in RT, such as intensity-modulated RT (IMRT) and image-guided RT (IGRT), have enhanced tumor targeting and minimized adjacent healthy tissue irradiation while also expanding RT to the recurrent or metastatic setting. Innovative therapeutic strategies for HNC integrate RT with immunotherapy, gene therapy, molecular targeted therapy, photodynamic therapy, photothermal therapy, and nanoparticles (NPs), with the objective of optimizing tumor control while reducing damage to normal tissues. NPs are emerging as possible radiosensitizers in HNC treatment, enhancing the efficacy of RT, chemotherapy, and immunotherapy. In vivo and in vitro studies on the irradiation of tumors containing gold (Au), gadolinium (Gd), and hafnium oxide (HfO₂) NPs show promising results in enhancing tumor destruction and survival rates, indicating their potential for clinical application. Hyperthermia, investigated as an adjunct treatment, potentially improves outcomes when combined with RT or chemotherapy, with advancements in nanotechnology renewing interest in this approach in HNC. At present, NBTXR3 is the sole NP that is being investigated in clinical trials for the enhancement of HNC RT.