Search Results (141)

Background/Objectives: During the repair of a wounded epithelium, keratinocytes become invasive via the epithelial-to-mesenchymal transition (EMT) process. Usually temporary and controlled, EMT persists in a chronically inflamed epithelium and is exacerbated in epithelial dysplasia and dysregulated in invasive carcinomas. Here we investigated the effects that IL-1 beta, IL-6, and IL-8, inflammatory cytokines expressed in specimens from OPMDs and OSCCs, have on NOKs and OSCC cells. Methods: AKT activation and EMT induction were assessed along with cellular invasiveness. Results: IL-1 beta, IL-6, and IL-8 induced EMT in NOKs, ex novo conferring them invasive capacity. The same cytokines exacerbated the constitutive EMT and invasiveness of OSCC cells. Since these phenomena were accompanied by AKT activation, we tested whether they could be influenced by RTV, a long-used anti-HIV drug that was previously found to block the activation of human AKT and exert antitumor effects. We observed that therapeutic amounts of RTV counteract all the above-mentioned tumorigenic activities of ILs. Finally, consistent with the key role that AKT and EMT play in OSCC radio-resistance, RTV increased OSCC cells’ sensitivity to therapeutic doses of ionizing radiation. Conclusions: These preliminary in vitro findings encourage the use of RTV to prevent the malignant evolution of OPMDs, reduce the risk of OSCC metastasis, and improve the outcomes of anti-OSCC radiotherapy. Full article

Background: Uvulopalatopharyngoplasty (UPPP) and expansion sphincter pharyngoplasty (ESP) are two standard surgical procedures for the treatment of snoring and obstructive sleep apnea. In a retrospective clinical trial, we compared the two surgical techniques regarding objective sleep parameters and patients’ reported outcomes. Materials and Methods: Patients treated with UPPP or ESP between January 2016 and February 2020 were included in this retrospective clinical trial. Pre- and postoperative AHI, BMI, and smoking habits were recorded. Subjective improvement was assessed by the ESS score and symptom relief reported by patients and their bed partners. Results: Between 2016 and 2020, 114 patients were included in the study, 74 patients suffered from OSA, and 30 patients had non-apnoeic snoring (AHI < 5/h). No preoperative sleeping studies were available in 10 patients (10/114; 9%). Based on the findings during drug-induced sedation endoscopy, most patients received an ESP (71/114, 62%), and 43 patients received a UPPP (43/114, 38%). Additionally, in 52/114 (46%), radio frequency ablation of the tongue base was performed if DISE revealed retrolingual collapse. ESP reduced AHI from 21.1 ± 10.8/h to 13.3 ± 12.1/h (p = 0.04), whereas UPPP caused a non-significant decrease in the AHI from 25.0 ± 13.8/h to 18.2 ± 14.6/h (p = 0.6). A minor secondary bleeding was observed in 32 patients, which was effectively treated with electrocautery or conservative therapy (32/114). This was more common in the ESP group (22/71; 31%) than in the UPPP group (10/43; 23%). Postoperative need for analgesics was higher in the ESP group than in the UPPP group. The ESS score showed no significant improvement after UPPP or ESP (p = 0.3), but subjective improvement in snoring was reported by 87/114 (76%) patients. Conclusion: AHI reduction was significantly higher in the ESP patient group than in the UPPP group. ESP patients had a slightly higher rate of minor secondary bleeding and postoperative need for analgesics than UPPP patients. Full article

Ready-to-eat meals (RTEMs) are increasingly popular due to their convenience, but ensuring their safety and quality presents significant challenges. This comprehensive review analyzes recent technological advancements in RTEM safety control throughout the entire supply chain, from raw material sourcing to consumer consumption. We examine cutting-edge detection methods, including chromatography–mass spectrometry, real-time PCR, and CRISPR-based techniques for contaminants such as pesticide residues, veterinary drugs, heavy metals, and microorganisms. The review also explores innovative sterilization processes, such as irradiation, microwave, and radio frequency technologies, emphasizing their impact on microbial safety and product quality. Furthermore, we discuss the crucial role of packaging innovations, including modified atmosphere packaging, functional antimicrobial materials, and intelligent packaging systems, in preserving RTEM freshness and extending shelf life. This review provides valuable insights into current trends and future directions in RTEM safety and quality control, aiming to contribute to sustainable growth and consumer confidence in this rapidly expanding industry. Full article

The emergence of nanotechnology in medicine, particularly using iron oxide nanoparticles (IONPs), may impact cancer treatment strategies. IONPs exhibit unique properties, such as superparamagnetism, biocompatibility, and ease of surface modification, making them ideal candidates for imaging, and therapeutic interventions. Their application in targeted drug delivery, especially with traditional chemotherapeutic agents like cisplatin, has shown potential in overcoming limitations such as low bioavailability and systemic toxicity of chemotherapies. Moreover, IONPs, by releasing iron ions, can induce ferroptosis, a form of iron-dependent cell death, which offers a promising pathway to reverse radio- and chemoresistance in cancer therapy. In particular, IONPs demonstrate significant potential as radiosensitisers, enhancing the effects of radiotherapy by promoting reactive oxygen species (ROS) generation, lipid peroxidation, and modulating the tumour microenvironment to stimulate antitumour immune responses. This review explores the multifunctional roles of IONPs in radiosensitisation through ferroptosis induction, highlighting their promise in advancing treatment for head and neck cancers. Additional research is crucial to fully addressing their potential in clinical settings, offering a novel approach to personalised cancer treatment. Full article

Localization in the central nervous system, diffuse growth, the presence of stem cells, and numerous resistance mechanisms, all make glioblastoma (GBM) an incurable tumor. The standard treatment of GBM consisting of surgery; radio- and chemotherapy with temozolomide provides insufficient therapeutic benefit and needs to be updated with effective modern solutions. One of the most promising and intensively explored therapeutic approaches against GBM is the use of nanotherapy. The first, and so far only, nanoparticle-based therapy approved for GBM treatment is NanoTherm^TM. It is based on iron oxide nanoparticles and the thermal ablation of the tumor with a magnetic field. Numerous other types of nanotherapies are being evaluated, including polymer and lipid-based nanoformulations, nanodiscs, dendrimers, and metallic, silica, or bioderived nanoparticles, among others. The advantages of these nanoscale drug carriers include improved penetration across the blood–brain barrier, targeted drug delivery, biocompatibility, and lower systemic toxicity, while major problems with their implementation involve scaling up their production and high costs. Nevertheless, taking all the impressive benefits of nanotherapies into consideration, it seems obvious that the combined effort of the scientific world will need to be taken to tackle these challenges and implement these novel therapies into clinics, giving hope that the battle against GBM can finally be won. Full article

Non-small cell lung carcinoma (NSCLC) comprises the majority of lung cancer cases, characterized by a complex interplay of genetic alterations, environmental factors, and molecular pathways contributing to its pathogenesis. This article highlights the multifaceted pathogenesis of NSCLC and discusses screening and integrated strategies for current treatment options. NSCLC is an evolving field with various aspects including the underlying molecular alterations, oncogenic driver mutations, and immune microenvironment interactions that influence tumor progression and response to therapy. Surgical treatment remains the most applicable curative option, especially in the early stages of the disease, adjuvant chemotherapy may add benefits to previously resected patients. Combined Radio-chemotherapy can also be used for palliative purposes. There are various future perspectives and advancing horizons in NSCLC management, encompassing novel therapeutic modalities and their applications, such as CAR-T cell therapy, antibody-drug conjugates, and gene therapies. On the other hand, it’s crucial to highlight the efficacy of innovative modalities of Immunotherapy and immune checkpoint inhibitors that are nowadays widely used in treatment of NSCLC. Moreover, the latest advancements in molecular profiling techniques and the development of targeted therapies designed for specific molecular alterations in NSCLC play a significant role in its treatment. In conclusion, personalized approaches are a cornerstone of successful treatment, and they are based on a patient’s unique molecular profile, tumor characteristics, and host factors. Entitling the concept of individualized treatment strategies requires proper patient selection, taking into consideration mechanisms of resistance, and investigating potential combination therapies, to achieve the optimal impact on long-term survival. Full article

(1) Background/Objectives: Primary and secondary brain tumours often hold devastating prognoses and low survival rates despite the application of maximal neurosurgical resection, and state-of-the-art radiotherapy and chemotherapy. One limiting factor in their management is that several antineoplastic agents are unable to cross the blood–brain barrier (BBB) to reach the tumour microenvironment. Nanomedicine could hold the potential to become an effective means of drug delivery to overcome previous hurdles towards effective neuro-oncological treatments. (2) Methods: A scoping review following the PRISMA-ScR guidelines and checklist was conducted using key terms input into PubMed to find articles that reflect emerging trends in the utilisation of nanomedicine in drug delivery for primary and secondary brain tumours. (3) Results: The review highlights various strategies by which different nanoparticles can be exploited to bypass the BBB; we provide a synthesis of the literature on the ongoing contributions to therapeutic protocols based on chemotherapy, immunotherapy, focused ultrasound, radiotherapy/radiosurgery, and radio-immunotherapy. (4) Conclusions: The emerging trends summarised in this scoping review indicate encouraging advantageous properties of nanoparticles as potential effective drug delivery mechanisms; however, there are still nanotoxicity issues that largely remain to be addressed before the translation of these innovations from laboratory to clinical practice. Full article

To enhance the treatment of tumors that are resistant to radio- and chemotherapy while minimizing the side effects of radiochemotherapy, researchers are continuously seeking new active compounds for use in combination with radiotherapy. Therefore, the aim of our study was to examine the cytotoxic and radiosensitizing effects of an extract from St. John’s Wort (Hypericum perforatum), referred to as HP01, on human epithelial tumor cells in vitro. The growth of MCF-7 (breast carcinoma) and HT-29 (colon carcinoma) cells was examined under the influence of HP01. In combination with radiation, the effects of HP01 on cytotoxicity and long-term survival were assessed using a colony formation assay. The number of DNA double-strand breaks was analyzed using the γH2AX assay, while cell cycle distribution was examined via flow cytometry. A growth-inhibiting and cytotoxic effect was observed for both tumor cell lines starting at a concentration of 10 µg/mL HP01. Treatment with HP01 resulted in an inhibition of clonogenic survival of tumor cells after ionizing radiation (6 Gy). The number of DNA double-strand breaks (DSBs) in tumor cells increased with HP01 treatment, but the repair of radiation-induced DNA DSBs was not affected. Cell cycle analysis revealed that HP01, in addition to radiation, enhanced G2/M arrest in MCF-7 and HT-29 cells. Overall, HP01 not only showed a growth-inhibiting effect but also demonstrated a radiosensitizing effect on human tumor cells for the first time. We conclude that the HP01-induced G2/M accumulation of cells may be the main rationale for the drug-induced radiosensitivity. It is therefore a promising candidate for combined therapy in tumor diseases and warrants further investigation. Full article

Conventional endoscopy is limited in its ability to examine the small bowel and perform long-term monitoring due to the risk of infection and tissue perforation. Wireless Capsule Endoscopy (WCE) is a painless and non-invasive method of examining the body’s internal organs using a small camera that is swallowed like a pill. The existing active locomotion technologies do not have a practical localization system to control the capsule’s movement within the body. A robust localization system is essential for safely guiding the WCE device through the complex gastrointestinal (GI) tract. Moreover, having access to the capsule’s trajectory data is highly desirable for drug delivery and surgery, as well as for creating accurate user profiles for diagnosis and future reference. Therefore, a robust, real-time, and practical localization system is imperative to advance the field of WCE and make it desirable for clinical trials. In this work, we have identified salient features of different localization techniques and categorized studies in comprehensive tables. This study is self-contained as it offers a comprehensive overview of emerging localization techniques based on magnetic field, radio frequency (RF), video, and hybrid methods. A summary at the end of each method is provided to point out the potential gaps and give directions for future research. The main point of this work is to present an in-depth review of the most recent localization techniques published in the past five years. This will assist researchers in comprehending current techniques and pinpointing potential areas for further investigation. This review can be a significant reference and guide for future research on WCE localization. Full article

The primary method of treatment for patients suffering from drug-resistant focal-onset epilepsy is resective surgery, which adversely impacts neurocognitive function. Radio frequency (RF) ablation and laser ablation are the methods with the most promise, achieving seizure-free rates similar to resection but with less negative impact on neurocognitive function. However, there remains a number of concerns and open technical questions about these two methods of thermal ablation, with the primary ones: (1) heating; (2) hemorrhage and bleeding; and (3) poor directionality. Irreversible electroporation (IRE) is a proven method of focal ablation, which circumvents all three of the primary concerns regarding focal RF and laser ablation. Here, we demonstrate the in vivo application of a flexible implant with organic electrodes for focal ablation of epilepsy foci using high-frequency IRE (H-FIRE) in mice. Our results show that local, targeted ablation is possible in the close neighborhood of the electrode, paving the way for the clinical application in the treatment of focal epilepsy. Full article

Objective: Currently, ⁶⁸Ga-labeled somatostatin analogs (SSAs) are the most commonly used imaging agents for patients with neuroendocrine tumors (NETs) in clinical practice, demonstrating good results in tumor diagnosis. For applications in peptide receptor radionuclide therapy (PRRT), targeted drugs should have high tumor uptake and prolonged tumor retention time. To enhance the uptake and retention of tracers in NETs, our goal is to design a ⁶⁸Ga-labeled heterodimer for optimizing pharmacokinetics and assess whether this form is more efficacious than its monomeric equivalents. Methods: Using the somatostatin analog TATE and quinoline-based compound FAPI-46 as raw materials, we designed and synthesized ⁶⁸Ga-labeled TATE-46. The labeling efficiency and stability were verified by Radio-HPLC. The receptor binding properties and tumor targeting were examined both in vitro and in vivo by using NCI-H727 (SSTR2/FAP, positive) and Mc38 (SSTR2/FAP, negative) cell lines and tumor-bearing mouse models. Preclinical evaluation was performed through cell uptake, pharmacokinetics, Micro PET, and biodistribution studies, and the results were compared with [⁶⁸Ga]Ga-DOTA-TATE and [⁶⁸Ga]Ga -FAPI-46. Immunohistochemistry and HE staining were performed on tumor tissues from tumor-bearing mice for further validation. Results: [⁶⁸Ga]Ga-TATE-46 showed comparable SSTR2 and FAP targeting ability to monomeric TATE and FAPI-46 in cell uptake and PET imaging studies. [⁶⁸Ga]Ga-TATE-46 exhibited significantly higher uptake in NCI-H727 (SSTR2/FAP, positive) tumors compared to [⁶⁸Ga]Ga-DOTA-TATE (p < 0.001) and [⁶⁸Ga]Ga-FAPI-46 (p < 0.001). No increased uptake of [⁶⁸Ga]Ga-TATE-46 was observed in MC38 tumors (SSTR2/FAP, negative). Additionally, excess DOTA-TATE and/or unlabeled FAPI-46 significantly blocked the uptake of [⁶⁸Ga]Ga-TATE-46 in NCI-H727 tumors (p < 0.001), confirming its dual-receptor targeting characteristics. The ex vivo biodistribution, immunofluorescence and immunohistochemistry results were in line with the in vivo imaging findings. Conclusion: Compared with ⁶⁸Ga-labeled FAPI-46 and DOTA-TATE mono-specific tracers, the dual-target tracer [⁶⁸Ga]Ga-TATE-46 improves tumor uptake, extends tumor retention, and enhances pharmacokinetics. It is an effective probe for non-invasive detection of tumors expressing FAP and SSTR2, and it is worth further studying its application in the expression of sstr2 and FAP-related tumors. Full article

Background/Objectives: Conventional anticancer therapies often lack specificity, targeting both cancerous and normal cells, which reduces efficacy and leads to undesired off-target effects. An additional challenge is the presence of hypoxic regions in tumors, where the Hypoxia Inducible Factor (HIF) transcriptional system drives the expression of pro-survival and drug resistance genes, leading to radio- and chemo-resistance. This study aims to explore the efficacy of targeted nanoparticle (NP)-based small interfering RNA (siRNA) therapies in downregulating these genes to enhance treatment outcomes in pancreatic cancer, a tumor type characterized by high CD44 expression and hypoxia. Methods: We utilized hyaluronic acid (HA)-displaying nanoparticles composed of positively charged chitosan (CS) complexed with siRNA to target and knock down HIF-1α in pancreatic cancer cells. Two NP formulations were prepared using either low molecular weight (LMW) or high molecular weight (HMW) CS. These formulations were evaluated for their internalization by cells and their effectiveness in gene silencing, both in vitro and in vivo. Results: The study found that the molecular weight (MW) of CS influenced the interaction between HA and CD44, as well as the release of siRNA upon internalization. The LMW CS formulation shows faster uptake kinetics, while HMW CS is more effective in gene knockdown across different cell lines in vitro. In vivo, both were able to significantly knockdown HIF-1α and some of its downstream genes. Conclusions: The results suggest that HMW and LMW CS-based NPs exhibit distinct characteristics, showing that both MWs have potential for targeted pancreatic cancer therapy by influencing different aspects of delivery and gene silencing, particularly in the hypoxic tumor microenvironment. Full article

Glioblastoma (GBL) is one of the more malignant primary brain tumors; it is currently treated by a multimodality strategy including surgery, and radio- and chemotherapy, mainly consisting of temozolomide (TMZ)-based chemotherapy. Tumor relapse often occurs due to the establishment of TMZ resistance, with a patient median survival time of <2 years. The identification of natural molecules with strong anti-tumor activity led to the combination of these compounds with conventional chemotherapeutic agents, developing protocols for integrated anticancer therapies. Curcumin (CUR), resveratrol (RES), and its glucoside polydatin (PLD) are widely employed in the pharmaceutical and nutraceutical fields, and several studies have demonstrated that the combination of these natural products was more cytotoxic than the individual compounds alone against different cancers. Some of us recently demonstrated the synergistic efficacy of the sublingual administration of a new nutraceutical formulation of CUR+PLD in reducing tumor size and improving GBL patient survival. To provide some experimental evidence to reinforce these clinical results, we investigated if pretreatment with a combination of CUR+PLD can improve TMZ cytotoxicity on GBL cells by analyzing the effects on cell cycle, viability, morphology, expression of proteins related to cell proliferation, differentiation, apoptosis or autophagy, and the actin network. Cell viability was assessed using the MTT assay or a CytoSmart cell counter. CalcuSyn software was used to study the CUR+PLD synergism. The morphology was evaluated by optical and scanning electron microscopy, and protein expression was analyzed by Western blot. Flow cytometry was used for the cell cycle, autophagic flux, and apoptosis analyses. The results provide evidence that CUR and PLD, acting in synergy with each other, strongly improve the efficacy of alkylating anti-tumor agents such as TMZ on drug-resistant GBL cells through their ability to affect survival, differentiation, and tumor invasiveness. Full article

High levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2 and angiopoietin (ANG)-2 are found in tissues from oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). As might be expected, VEGF, FGF-2, and ANG-2 overexpression parallels the development of new blood and lymphatic vessels that nourish the growing OPMDs or OSCCs and provide the latter with metastatic routes. Notably, VEGF, FGF-2, and ANG-2 are also linked to the epithelial-to-mesenchymal transition (EMT), a trans-differentiation process that respectively promotes or exasperates the invasiveness of normal and neoplastic oral epithelial cells. Here, we have summarized published work regarding the impact that the interplay among VEGF, FGF-2, ANG-2, vessel generation, and EMT has on oral carcinogenesis. Results from the reviewed studies indicate that VEGF, FGF-2, and ANG-2 spark either protein kinase B (AKT) or mitogen-activated protein kinases (MAPK), two signaling pathways that can promote both EMT and new vessels’ formation in OPMDs and OSCCs. Since EMT and vessel generation are key to the onset and progression of OSCC, as well as to its radio- and chemo-resistance, these data encourage including AKT or MAPK inhibitors and/or antiangiogenic drugs in the treatment of this malignancy. Full article

Clinical trials, by contributing to the development of diagnostics and to the search for modern, more effective, and safer therapies, have become one of the most important elements of the healthcare system. They enable the introduction of innovative drugs and treatments that can significantly improve patients’ quality of life. Not only does this research help to understand disease mechanisms, but it also enables the personalization of therapy, which often increases the effectiveness of treatment. Public awareness of clinical trials helps build trust in science and medicine, which is fundamental to the effective functioning of the healthcare system. The aim of this study was to assess Poles’ knowledge and beliefs about clinical trials. Methods: The survey was conducted among Poles aged 18 and over with the help of an external company, Ariadna, which is an independent research panel. The questionnaire contained 22 questions, of which 13 questions concerned beliefs and attitudes towards clinical trials. Results: One thousand and seventy-nine participants took part in the study (n = 1079). The mean age of respondents was 44.96 years (SD = 16.30). Slightly more women (n = 568, 52.6%) than men (n = 511, 47.4%) took part in the study. Among the respondents, 86.5% (n = 933) were aware of clinical trials. The main sources of information about clinical trials were the media (53.8%) including the Internet (n = 355, 32.9%), TV (n = 175, 16.2%), press (n = 30, 2.8%), and radio (n = 21, 1.9%). 43.2% (n = 466) of respondents reported little knowledge of clinical trials, while more than three quarters (n = 805, 75.2%) said they would like to learn more about clinical trials. Most respondents (n = 879, 81.4%) agreed with the statement that participation in a clinical trial is completely voluntary, and more than half (n = 580, 53.7%) agreed with the statement that hospitals participating in clinical trials provide better healthcare. The statement that the results of clinical trials are made available to the public was disagreed with by 37.2% (n = 402) of participants. Only 30.3% (n = 327) of participants agreed that clinical trials should be conducted with children. Most respondents (n = 638, 59.1%) agreed with the statement that a patient in a clinical trial is insured. 48.3% (n = 521) of participants are aware that a clinical trial can be withdrawn from at any time. Conclusions: Poles rate their knowledge of clinical trials as low and would like to learn more. Poles’ knowledge of clinical trials is mainly based on commercial sources. Full article