Oncological Diseases Research Articles

Abstract PR007: To the tumor and beyond: Tales of a holistic miRNA delivery vehicle

Abstract Like the challenges and skepticism that faced the antibody therapeutics field over a decade ago, RNA therapeutics is facing the same. And, like the antibody therapeutics field, we are beginning to realize the clinical impact of RNA therapeutics amiss these challenges. This is most clearly highlighted with the recent approval of mRNA vaccines and RNAi drugs targeted to the liver. Unfortunately, RNA-based drugs targeted to tumors is lagging behind, even with countless years of work that has revealed the power of using RNAi for treating oncological diseases. Lack of success is attributed to inability to deliver RNAi safely and effectively. A successful delivery agent requires multiple features. First, the agent must deliver the RNA specifically to the intended cells. Second, the agent must have a large therapeutic window, meaning that toxicity, if observed, should occur at doses that are orders of magnitude higher than the therapeutic dose. Third, if delivery of the RNA is by way of a specific ligand and receptor pair, as is the case herein, the RNA must successfully escape the endosome. Simply swelling the endosome is not enough if noncovalent interactions between the ligand and the receptor cannot be disrupted. Fourth, the RNA should include appropriate stabilizing modifications to increase intracellular half-life that will reduce dosing and cost. Through hard work and dedication, we have come up with an inclusive, easily synthesized, intramolecular molecule that achieves all of these essential features. Here, the challenges we face, the hurdles we have overcome, and the barriers that still remain with achieving success in reveling the clinical potential of miRNAs as anti-cancer therapeutics will be presented. Citation Format: Andrea L Kasinski. To the tumor and beyond: Tales of a holistic miRNA delivery vehicle [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr PR007.

Pharmacovigilance study of tyrosine kinase inhibitors: Analysis of adverse reactions

The aim of the study is to analyze reports of adverse drug reactions published in the scientific literature occurring during and after the use of kinase inhibitors for the treatment of rheumatologic diseases to determine their type, frequency, and severity. The search was conducted in the MEDLINE and PubMed databases from January 2005 to May 2022. We found a total of 291 publications, from which we selected suitable ones for data extraction. We conducted descriptive and variation analyses as the main statistical analyses. We determined mean values, standard deviation, minimum, maximum, and 95% confidence intervals. The PICOS tool was used to evaluate the results. The analyzed population includes patients with rheumatologic and oncologic diseases. There is a significant interest in the drug safety of kinase inhibitors, as they represent a rapidly evolving and reliable pharmacological class. Clarifying the safety profile of their representatives remains important. In-depth review of full-text publications shows that the high frequency of reported serious ADRs is rather due to increased interest in reporting and publishing these cases than to their high frequency of occurrence.

OncoSexome: the landscape of sex-based differences in oncologic diseases

Abstract The NIH policy on sex as biological variable (SABV) emphasized the importance of sex-based differences in precision oncology. Over 50% of clinically actionable oncology genes are sex-biased, indicating differences in drug efficacy. Research has identified sex differences in non-reproductive cancers, highlighting the need for comprehensive sex-based cancer data. We therefore developed OncoSexome, a multidimensional knowledge base describing sex-based differences in cancer (https://idrblab.org/OncoSexome/) across four key topics: antineoplastic drugs and responses (SDR), oncology-related biomarkers (SBM), risk factors (SRF) and microbial landscape (SML). SDR covers sex-based differences in 2051 anticancer drugs; SBM describes 12 551 sex-differential biomarkers; SRF illustrates 350 sex-dependent risk factors; SML demonstrates 1386 microbes with sex-differential abundances associated with cancer development. OncoSexome is unique in illuminating multifaceted influences of biological sex on cancer, providing both external and endogenous contributors to cancer development and describing sex-based differences for the broadest oncological classes. Given the increasing global research interest in sex-based differences, OncoSexome is expected to impact future precision oncology practices significantly.

Abstract 4137737: Demographics and Factors Influencing Mortality Among Cardiac Angiosarcoma Patients: An Analysis of the SEER Database

Background and Aims: Cardiac angiosarcoma is a rare and highly aggressive cancer originating from the endothelial cells lining the heart. It accounts for approximately 30% of all primary cardiac tumors. Given its aggressive nature and poor prognosis, it is critical to enhance our understanding of its epidemiology and the factors influencing mortality. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was utilized to gather data spanning from 2000 to 2021 using the International Classification of Diseases for Oncology (ICD-O-3), anatomical codes (C38.0-Heart), and histological code 9120. Results: We identified 194 patients with cardiac angiosarcoma, of which 102 were males and 92 were females. The majority of patients were aged 50 years or younger (59%). Non-Hispanic whites constituted the largest group (56%), followed by non-Hispanic blacks (18%), and Hispanics (16%). Mortality data showed that 91% of the diagnosed patients died (n=176), with a mean survival period of 15 months after diagnosis. The overall survival rate at 1 year was 0.461 (95% CI: 0.39-0.53), at 3 years was 0.09 (95% CI: 0.05-0.14) and at 5 years was 0.052 (95% CI: 0.03-0.10). Advanced age (51-70 years) compared to the 0-50 year age group (HR: 0.57; 95% CI: 0.003-1.14; p=0.049), distant stage (HR: 0.91; 95% CI: 0.01-1.83; p=0.047), patients who did not receive therapeutic radiation therapy compared to those who did (HR: 2.69; 95% CI: 0.10-5.28; p=0.042), and patients who did not undergo surgical resection for angiosarcoma compared to those who did (HR=1.232; 95% CI: 0.69-1,77; p<0.001) were factors associated with increased mortality. Female gender (p=0.248, as compared to males), different races of non-Hispanic White (p=0.849), non-Hispanic Black (p=0.34), non-Hispanic Asian or Pacific Islander (p=0.24), as compared to Hispanics, tumor sizes of 6-10 cms (p=0.957), or more than 10 cm (p=0.273), as compared to < 5 cm, grade of tumor (III; p=0.682, and grade IV; p=0.281, as compared to grade I), median household income of more than 65000 USD (p=0.069) as compared to less than that, and no chemotherapy (p=0.851) compared to those that received chemotherapy, were not associated with a significant increase in mortality. Conclusions: Cardiac angiosarcoma is associated with a high mortality rate. Factors contributing to increased mortality include advanced age, distant stage of disease at diagnosis, not receiving radiation therapy, and not undergoing surgical resection.

INTEGRATIVE ONCOLOGY AS A PROMISING VECTOR FOR THE TREATMENT OF CANCER TREATMENT

The article presents an analysis of the possibilities for early diagnosis, treatment, and rehabilitation of patients with cancer within the framework of integrative oncology. Introduction. Oncological diseases remain one of the most pressing medical challenges of our time, driven by a steady increase in incidence, late-stage diagnoses, and unsatisfactory treatment outcomes. WHO experts predict that by 2050, the number of new cancer cases will rise by 77% compared to 2022. Despite significant advancements in diagnostics and conventional treatments, including surgery, chemotherapy, and radiotherapy, there remains a need for a more holistic approach. This approach would not only target tumor control but also aim to enhance the overall quality of life for patients. Discussion. Timely and accurate diagnosis is a crucial aspect of the fight against cancer. Early detection can significantly improve the chances of successful treatment and patient survival. However, conventional cancer treatments are often aggressive, leading to complications, side effects, and patient disability. Integrative oncology combines traditional therapies with complementary approaches, focusing on maintaining overall patient health, reducing side effects, facilitating restorative rehabilitation, and enhancing quality of life. This comprehensive, integrative approach broadens and strengthens the options for cancer treatment, offering a more holistic care strategy. Conclusion. Integrative oncology represents a promising direction in cancer treatment by providing a comprehensive approach to addressing the disease. The combination of conventional treatments with complementary therapies not only enhances treatment effectiveness but also significantly improves patient quality of life, an essential aspect in the ongoing battle against cancer.

Expediting treatments in the 21st century: orphan drugs and accelerated approvals

BackgroundIn response to activated patient communities’ catalyzation, two significant efforts by the FDA to expedite treatments have now been in place for multiple decades. In 1983, the United States Congress passed the Orphan Drug Act to provide financial incentives for development of drugs for rare diseases. In 1992, partly in response to the HIV epidemic, the FDA implemented Accelerated Approval (AA) to expedite access to promising new therapies to treat serious conditions with unmet medical need based on surrogate marker efficacy while additional clinical data is confirmed.The uses of these regulatory approaches over time are assessed in this study.MethodsThe following U.S. FDA CDER published lists were used in this analysis: 1. all orphan designations and approvals; 2. all AA and their details updated through December 31, 2022; new molecular entities (NMEs).ResultsOrphan drug designations and approvals have increased several-fold over the past four decades. The largest increase recently has been in therapies targeting oncological diseases (comprised of both oncology and malignant hematology).Although orphan drug approvals based on NMEs are the minority of orphan drug designations, the count of approved orphan drug NMEs has increased in recent years.The characteristics of orphan drug approvals show notable differences by disease area with rare diseases and medical genetics (49%) having a relatively large fraction of orphan drug approvals with NMEs compared to the oncological diseases (32%).Similar to the use of orphan drug designation, oncological disease therapies have been the largest utilizers of AA. Many therapies targeting these diseases address unmet medical need and can leverage surrogate markers that have previously been used in similar trials.The timings of conversion of AA (confirmed or withdrawn) were assessed and found to be consistent across decades and to have some dependency upon the broad disease area (when assessed by three large groups: HIV conversions were fastest; followed by oncology; followed by all others). By the end of 2022, 98% of the first 105 (approved in 2010 or earlier) AA had been converted to confirmed or withdrawn.ConclusionsAlthough the typical timings for AA to be confirmed or withdrawn has not changed significantly over the decades, the disease areas utilizing orphan drug designation and AA have changed significantly over time. Both programs have had increases in their use for therapies targeting oncological diseases.The re-use of surrogate markers for oncological diseases has been an advantage in a way that may not be scientifically feasible in many other disease areas that have greater differentiation across disease etiology. For non-oncological diseases, applicability of AA is, in part, dependent upon greater focus on characterization and acceptance of novel surrogate markers.

Bibliometric analysis of scientific literature on the use of suppositories in the treatment of prostate cancer patients

Nowadays, cancer remains one of the main causes of death worldwide. Statistical data from various literary sources indicate that more than 130,000 people in Ukraine receive this diagnosis as a sentence every year. Cancer can affect any organs of the human body and, over time, the entire organism. In 2024, the agency of the World Health Organization on cancer and the International Agency of Cancer Research published the latest statistical estimates of this pathology in a global format, where prostate cancer is among the five most common oncological pathologies and takes the fourth place. Oncological diseases are one of the priority areas of healthcare development in accordance with the Order of the Ministry of Health of Ukraine No. 1832 dated 07.10.2022 “On Approval of Priority Areas of Healthcare Development for 2023–2025”. It was this fact that determined the choice of the direction of this research in the matter of finding information on the provision of pharmaceutical care, namely the use of a drug – a rectal suppository for the treatment of prostate cancer. The aim of the work is to carry out a bibliometric analysis and further generalize the data of the scientific literature to study the prognostic value and features of the prescription of suppositories in the treatment of prostate cancer. Materials and methods. The data search was conducted in the PubMed electronic database using the following key terms: “prostate cancer and suppositories”, “prostate cancer”. To monitor and analyze international scientific research, with the help of visualization tools and modern SciVal citation metrics using the online platform, bibliometric analysis can be performed. Using the VOSviewer functional program, bibliometric networks were constructed and visualized. Results. A map of the relationships between the most used keywords on the topics of “prostate cancer” and “prostate cancer and suppositories”, grouped into clusters for the period from 1986 to 2024, was built. The clustering of the most used keywords on the subject of “prostate cancer” for the specified period is summarized. According to the bibliographic analysis, interest in the above topic was highest in 2014 and 2021. Conclusions. According to the bibliographic analysis, the interest in the subject of the patients’ treatment with prostate cancer disease continues to grow from 1998 up to the present. The analysis of publication activity using the visualization tool of bibliometric networks VOSviewer for the period from 2014 to 2024 for the key words “prostate cancer” has shown the presence of 14 clusters. The largest cluster is devoted to modern methods of prostate cancer treatment, studies of gene rearrangement, target therapy, carcinogenesis.

Military medicine of modern hybrid wars

During the hybrid armed conflict in which Russia became involved — the Special Military Operation — the medical service of the Armed Forces faced a number of challenges. This review analyzes foreign publications indexed in PubMed® concerning the conditions and factors affecting the activities of the medical services of armed forces, primarily those of NATO countries. It was revealed that a limiting factor for operational effectiveness is the staffing levels and qualitative composition of medical personnel, their preparedness to provide care for the specific pathologies of wartime, and maintaining these competencies in an up-to-date state. Important conditions for successful provision of medical care are preserving the integrity of medical facilities during targeted attacks on them, and the ability to use infrastructure in hostile or newly occupied territories. Prehospital care serves as a limiting factor in reducing lethality, with the main causes being fatal hemorrhages and head injuries from mine-blast trauma. Proper tourniquet application, rapid evacuation, and blood transfusions make the greatest contribution to reducing prehospital mortality. Among casualties, those with limb wounds are most significant, as they subsequently create the greatest social burden on the state, exceeding the “years lived with disability” parameter for all other disease classes, including oncological and cardiovascular diseases. In modern conflicts, the most dangerous in terms of lethality are mine-blast injuries (61.4–83.5%) and head injuries (20.9–59.0%), and in terms of subsequent disease burden, limb injuries (45.7%) constitute an absolute majority and are the point of focus for the main efforts of the medical services of the warring states’ armed forces. At the same time, there are no unified approaches regarding the place of application of qualified and specialized care among countries.

Pathological changes on the skin due to the combined effects of polycyclic aromatic hydrocarbons and ultraviolet radiation

Introduction. In the National Healthcare Project, one of the key areas is the federal project "Fight against oncological diseases for 2019-2024". The influence of the nature of work activities of workers in contact with industrial carcinogens — polycyclic aromatic hydrocarbons (PAHs) significantly increases the risk of skin neoplasms, as evidenced by differences in the frequency of their occurrence among representatives of different labor categories. The leading factor in the development of skin neoplasms is ultraviolet radiation (UV) of the A and B spectrum. There is literature evidence of a possible mutual enhancement of the combined effects of PAHs and UV in the occurrence of skin neoplasms and their malignancy. The study aims to evaluate the role of the combined effects of polycyclic aromatic hydrocarbons (PAHs) and ultraviolet radiation (UV) in the occurrence of pigmented skin tumors in workers engaged in the construction of highways and highways and in housing and communal services. Materials and methods. During periodic medical examinations (PMEs) in 2022–2024, specialists have examined 140 people who formed 4 study groups. The researchers have conducted a physical examination of skin tumors; examination in the rays of a Wood lamp; dermatoscopy of skin tumors using a Heine Delta 20 dermatoscope. Hyperpigmentation was assessed according to the hyperpigmentation area and severity index (NASI). Results. During the clinical examination, the authors assessed the presence of pigmentation and skin neoplasms (lentigo, ephelides, seborrheic keratomas). The most frequent localizations of pigmentation and skin neoplasms were open areas of the body: face, hands, upper third of the back. At the same time, in asphalt concrete workers — group I, working under the influence of PAHs and solar insolation (spectrum A and B, in the range of 320–400 nm and 280–320 nm), specialists revealed pigmented neoplasms in a larger number of individuals compared with the population control for all skin localizations. The HASI index (in the surveyed groups) showed that the highest rates (24–48) of HASI were observed in a larger number of individuals — 57.1% — from group I (UV+PAHs), compared with groups of individuals (II, III, IV) who do not work under conditions of exposure to solar insolation (spectra A and B, in the range of 320–400 nm and 280–320 nm). The authors noted that the intensity of pigmentation is higher and the lesion area is larger when assessing the foci of hyperpigmentation in the rays of the Wood lamp compared with the clinical examination in all the examined groups. Limitations. The study is limited by the number of subjects examined, corresponding to the design of the study and the time interval of the study. Conclusion. To obtain objective results of the study of the role of the combined effects of polycyclic aromatic hydrocarbons (PAHs) and ultraviolet irradiation (UV) in the occurrence of pigmented skin tumors, scientists used a method for determining the hyperpigmentation area index and severity index (HASI) in the rays of a Wood's lamp. When comparing the results obtained, experts revealed an increase in the area of hyperpigmentation and its intensity with localization in open areas of the body in workers engaged in the construction of highways and housing and communal services, in contact with the combined effects of carcinogens (PAHs) and ultraviolet irradiation (UV A and B). Further in-depth studies are needed to study the etiopathogenesis of photogenotoxicity depending on the dose-effect ratio. Ethics. The work was performed in accordance with the ethical standard set out in the Helsinki Declaration of the World Medical Association of 1964 (as amended and supplemented in 2013). The authors conducted all the studies after receiving informed consent and a decision of the Local Ethics Committee (extract from Protocol No. 7 dated 10/21/2020).

Cancer survivors and cardiovascular diseases: from preventive strategies to treatment.

During the last decades, progress in the treatment of oncological diseases has led to an increase in the survival of cancer patients: cancer survivors (CS). Thus, the incidence of CS has increased enormously, in both adult CS and childhood and adolescent CS. Unfortunately, CS treated with anthracyclines, chest radiotherapy (RT) and other potentially cardiotoxic drugs have a higher risk of cardiovascular (CV) toxicity: heart failure with reduced ejection fraction (HFrEF), valve diseases, coronary artery diseases, vascular diseases and pericardial diseases. In fact, chest irradiation can cause coronary artery diseases that can be latent until at least 10 years after exposure; also, valvular heart diseases can appear after >20 years following irradiation; heart failure may appear later, several years after anticancer drugs or RT. Therefore, it is very important to stratify the CV risk of cancer patients at the end of cardiotoxic drugs, to plan the most appropriate long-term surveillance program, in accordance with 2022 ESC Guidelines on Cardio-Oncology, to prevent late cardiovascular complications. Monitoring of cancer patients must not stop during anticancer treatment but it must continue afterwards, depending on the patient's CV risk. CV toxicity risk should be reassessed 5 years after therapy to organize long-term follow-up. Considering late cardiotoxicity in CS, our review aims to evaluate the incidence of cardiovascular diseases in CS, their mechanisms, surveillance protocols, preventive strategies, diagnosis and treatment.

Emerging Technologies for the Assessment of Natural Killer Cell Activity

Understanding natural killer (NK) cell functionality is essential in developing more effective immunotherapeutic strategies that can enhance patient outcomes, especially in the context of cancer treatment. This review provides a comprehensive overview of both traditional and novel techniques for evaluating NK cell functionality, focusing on multiparameter assays and spatial methods that illuminate NK cell interactions within their microenvironment. We discuss the significance of standardized assays for assessing NK cell function across various research and clinical settings, including cancer immunotherapy, infectious diseases, and transplantation. Key factors influencing NK cell functionality include the origin of the sample, target–effector ratios, the functional state of NK cells, and the impact of pre-treatment conditions and their natural aging effect on NK cell activity. By emphasizing the importance of selecting a suitable technique for reliable measurements, especially for longitudinal monitoring, this review aims to give an overview on techniques to measure NK cell functionality in vitro and show the interaction with their microenvironment cells by spatial imaging. Ultimately, our understanding of NK cell functionality could be critical to biomarker development, drug design, and understanding of disease progression in the field of oncology or infectious disease.

Therapeutic Drug Monitoring of Antimicrobial Drugs in Children with Cancer: A New Tool for Personalized Medicine.

The risk of fungal, bacterial, and viral infections is higher in children with hematological and solid malignancies, particularly during periods of profound neutropenia. Although early administration of antimicrobial agents is common, optimizing pharmacological therapy in pediatric patients with cancer is challenging because of their variable pharmacokinetics compared with adults, including differences in body mass and augmented renal clearance, as well as chemotherapy-induced organ toxicity. Therapeutic drug monitoring, which involves measuring drug concentrations in serum or plasma at specific timepoints and adjusting doses accordingly, can be applied to various medications. While standardized targets for all antimicrobial agents in children are lacking, therapeutic drug monitoring appears to be beneficial in preventing serious toxicity and addressing treatment failure or non-compliance. This narrative review aims to analyze current perspectives on therapeutic drug monitoring for antimicrobial drugs in the special population of children with hematological or oncological diseases, including those undergoing hematopoietic cell transplantation. The review provides evidence on the clinical benefits of this method and explores potential future developments in this area.

USING ARTIFICIAL INTELLIGENCE FOR BIOMARKER ANALYSIS IN CLINICAL DIAGNOSTICS

Introduction. Artificial intelligence (AI) technologies are becoming crucial in clinical diagnostics due to their ability to process and interpret large volumes of data. The implementation of AI for biomarker analysis opens new opportunities in personalized medicine, offering more accurate and individualized approaches to disease diagnosis and treatment. The relevance of this review stems from the need to systematize recent advances in AI application for biomarker analysis, which is critical for early diagnosis and prediction of chronic non-communicable diseases (NCDs). Material and methods. The analysis of peer-reviewed scientific publications and reports from leading research centers over the past five years was conducted. Studies on the application of AI algorithms for analyzing genomic, proteomic, and metabolomic biomarkers were reviewed, including machine learning methods and deep neural networks. Special attention was paid to the integration of multi-marker panels for improving the accuracy of diagnosis and prediction of cardiovascular, digestive, respiratory, endocrine system diseases, as well as oncological and neurodegenerative pathologies. Results. The application of AI has significantly increased the sensitivity and specificity of diagnostics, especially in complex cases requiring analysis of multiple disease parameters. The effectiveness of AI has been demonstrated in early diagnosis of lung, breast, and colorectal cancer, prediction of cardiovascular complications and NCDs progression, including diabetes mellitus and Alzheimer’s disease. AI’s significant contribution to the discovery of new biomarkers, optimization of personalized treatment, and improvement of therapeutic strategies has been noted. Conclusion. The use of AI in biomarker analysis has become a significant breakthrough in medical diagnostics, particularly in oncology, cardiology, and neurodegenerative diseases. The technology allows integration of data about various biomarkers and contributes to creating more accurate models for disease diagnosis and prediction. Further development is associated with technology advancement and overcoming ethical and regulatory barriers, which will expand AI capabilities in clinical practice.

Mitochondrial donation as a mechanism of participation by mesenchymal stromal cells in regenerative processes

Mesenchymal stromal cells (MSCs) are universal regulators of regenerative processes due to their ability to secrete regulatory molecules or replace dead cells through differentiation in the appropriate direction. Recently, another mechanism for the beneficial effects of MSCs on damaged tissue has been discovered, such as the transfer of mitochondria into its cells in response to stress signals. MSCs can transfer mitochondria through tunneling nanotubes that form a communication bridge between cells, through gap junctions, by release as part of extracellular vesicles or in free form, and as a result of complete or partial fusion with recipient cells. In damaged cells that received mitochondria from MSCs, impaired energy metabolism is restored and oxidative stress is reduced, which is accompanied by increased survival, and in some cases also increased proliferation or a change in differentiation status. The restoration of energy after the transfer of mitochondria from MSCs has a beneficial effect on the functional activity of recipient cells and suppresses inflammatory reactions. A significant contribution of the MSC mitochondrial donation to the therapeutic efficacy of MSCs has been repeatedly demonstrated in models of damage to various organs in experimental animals. This stimulates the search for methods to enhance the process of mitochondrial donation. However, it should be taken into account that MSCs are able to transfer mitochondria to malignant cells as well, thereby stimulating tumor growth and increasing its resistance to chemotherapy. These data make it necessary to evaluate the prospects for the use of MSCs in cell therapy with caution. On the other hand, they can serve as a basis for the search for new therapeutic targets in the treatment of oncological diseases.

Photodynamic therapy – modern views and innovations in dentistry

Photodynamic therapy (PDT) consists of three elements: a photosensitizer, light and oxygen. The photosensitizer has the property of selective accumulation in target tissues without harming healthy cells. This innovative therapeutic method has already been successfully adapted in many areas of medicine, such as dermatology, gynecology, urology and oncology. PDT is also beginning to be introduced in dentistry. The antibacterial and fungicidal properties of the photosensitizer are used to achieve better results in the medical and surgical treatment of patients. Objective. To analyze current scientifi data on the application of photodynamic therapy (PDT) in various fi of dentistry, evaluate its effectiveness, and assess prospects for development. Materials and methods. A review of recent scientifi literature was conducted, including original studies, systematic reviews, and meta-analyses focused on PDT application in dentistry. Data on mechanisms of action, clinical efficacy, and new developments in PDT were analyzed. Results. High effi of PDT was established in the treatment of periodontal diseases, peri-implantitis, endodontic infections, and oral oncological diseases. Advantages of combined application of PDT with other treatment methods were noted. Promising directions for PDT development were identifi including the creation of new photosensitizers and technological innovations in equipment. Conclusions. PDT is a promising treatment method in dentistry, demonstrating high efficacyand safety. Further research is aimed at optimizing treatment protocols, developing personalized approaches, and integrating PDT with other modern technologies.

Difpad-Onco offers frailty screening by private practice nurses for elderly cancer patients

Difpad-Onco (nursing screening of the frailty of elderly people, at home, with oncological disease) aims to facilitate and complement the identification of frailties in elderly cancer patients by private practice nurses in the patient's home. It consists of the G8 Oncodage, a Mini-Cog screening for cognitive impairment, a history of falls, and social frailty. It is aimed at all cancer patients aged 70 and over. Around 80% of patients assessed have a G8 score ≤ 14/17, indicating geriatric frailty, and over 60% have more than one frailty (social, dietary, cognitive, falls). The DIFPAD-Onco project represents an innovative experiment in care pathways for elderly cancer patients.

Serotonin and adrenaline as inhibitors of neutrophil extracellular traps formation (experimental study)

Regulation of the NETosis can provoke cancer, inflammatory and autoimmune diseases and become a basis for effective targeted therapy. The aim: to study the modifying effects of serotonin and adrenaline on NETosis during phagocytosis in rats.Materials and methods.Wistar rats were divided into control (solvent, 0.9% NaCl solution) and experimental (serotonin and adrenaline 1.43 and 0.143 mg/kg body weight, respectively) groups. Intraperitoneal injection of test substances was carried out 90 minutes before blood sampling, in which phagocytic activity (PhA), phagocytic index (PhI) and degree of suicidal neutrophil NETosis were determined: with total and partial chromatin decondensation (TCD, PCD, accordingly). A paired Student’s t test was used to compare groups with numerical values and McNemar’s test (for dichotomous variables). Pearson’s linear correlation coefficient (rxy) was assessed to measure a linear relationship between time points.Results.The administration of adrenaline contributed to NETosis inhibition by 41.5% compared to control group (p 0.001), serotonin — by 27.6% (p 0.001). The ratio of neutrophils with total and partial chromatin decondensation for control group was 1.0:0.9; for serotonin and adrenaline it changed to 1.0:1.7 and 1.0:1.4, respectively. Relative to control group, phagocytic index after serotonin administration increased by 4.9%, in case of adrenaline, on the contrary, it decreased by 12.4% (p 0.01). A high positive correlation was revealed between NETosis and phagocytic index for control group and experimental group with adrenaline: rxy= 0.823–0.997. For phagocytic index and NETosis in these groups there was a high negative (rxy= –0.714–(–0.871)) and a noticeable positive correlation for serotonin (rxy= 0.638).Conclusion.Serotonin and adrenaline in therapeutic dosages have a pronounced inhibitory effect on NETosis, which may pave the avenue for increasing the effectiveness of therapy for immunoinflammatory and oncological diseases. The use of serotonin is preferable because it has additional immunomodulatory effects and cause no direct stimulation ofα- andβ-adrenergic receptors.

ОЦЕНКА И ПРОГНОЗИРОВАНИЕ РИСКА ПАЦИЕНТСКОГО НОН-КОМПЛАЕНСА В СИСТЕМЕ СПЕЦИАЛИЗИРОВАННОЙ ФАРМАЦЕВТИЧЕСКОЙ ПОМОЩИ НАСЕЛЕНИЮ С ОНКОЛОГИЧЕСКИМИ ЗАБОЛЕВАНИЯМИ

Cardiovascular, oncological and other diseases occupy a significant place in the structure of morbidity and causes of death of the population, the growth of which largely depends on lifestyle and risk factors. Identification of risk factors contributing to the development of cancer is one of the main achievements of epidemiology of the 21st century. Subsequent research helped scientists to build multifactorial algorithms for predicting the risks of cancer and mortality from them, which greatly facilitated the work of practitioners in the field of risk stratification. The above indicates that the research results of many foreign and domestic authors confirm that significant predictors of cancer are risk factors such as old age, pre-existing cancer in blood relatives, smoking, obesity, alcohol, certain types of viral infections, certain chemicals, ionizing radiation, including UV rays of the sun and others. It is known that reducing the influence of risk factors leads to a decrease in morbidity and mortality from cancer. An important condition in the treatment of oncological diseases is the rational and effective use of medicines. Pharmaceutical specialists play an active role in this process. In the treatment of long-term or lifelong diseases, such as cancer, great importance is attached to the process of daily pharmacotherapy, compliance with the rules of adherence to treatment or compliance. Thus, problems with patients performing medical appointments are based on a complex of factors, including psychological and behavioral ones, including patients' adherence to treatment.

Outcomes of female fertility preservation with cryopreservation of oocytes or embryos in the Netherlands: a population-based study.

What are the reproductive outcomes of patients who cryopreserved oocytes or embryos in the context of fertility preservation in the Netherlands? This study shows that after a 10-year follow-up period, the utilization rate to attempt pregnancy using cryopreserved oocytes or embryos was 25.5% and the cumulative live birth rate after embryo transfer was 34.6% per patient. Fertility preservation by freezing oocytes or embryos is an established treatment for women with a risk of premature ovarian failure (caused by a benign or oncological disease) or physiological age-related fertility decline. Little is known about the success of cryopreservation, the utilization rate of oocytes or embryos, or the live birth rates. A retrospective observational study was performed in the Netherlands. Data were collected between 2017 and 2019 from 1112 women who cryopreserved oocytes or embryos more than 2 years ago in the context of fertility preservation in 10 IVF centers in the Netherlands. A total of 1112 women were included in this study. Medical files and patient databases were used to extract data. Women were categorized based on indication of fertility preservation: oncological, benign, or non-medical. To indicate statistical differences the t-test or Mann-Whitney U test was used. Kaplan-Meier analyses were used for time endpoints, and log-rank analyses were used to assess statistical differences. The study protocol was approved by the medical ethics committee. Fertility preservation cycles have been performed increasingly over the years in the Netherlands. In the first years, less than 10 cycles per year were performed, increasing to more than 300 cycles per year 10 years later. Initially, embryos were frozen in the context of fertility preservation. In later years, cryopreservation of oocytes became the standard approach. Cryopreservation of oocytes versus embryos resulted in comparable numbers of used embryos (median of 2) for transfer and comparable live birth rates (33.9% and 34.6%, respectively). The 5-year utilization rate was 12.3% and the 10-year utilization rate was 25.5%. The cumulative clinical pregnancy rate was 35.6% and the cumulative live birth rate was 34.6% per patient. Those who had fertility preservation due to benign diseases returned earlier to use their cryopreserved embryos or oocytes. The follow-up period after the fertility preservation procedure varied between patients in this study and not all frozen oocytes or embryos had been used at the end of this study. This might have led to underestimated outcomes reported in this study. Furthermore, intention to treat cannot be fully determined since women who started the fertility preservation procedure without success (cancellation due to low response) were not included in this study. This study provides data on the reproductive outcomes after various indications of fertility preservation. This knowledge can be informative for professionals and future patients to improve counseling and informed decision making regarding ovarian stimulation in the context of fertility preservation. No funding was obtained for this study. The authors have no conflicts of interest to declare related to this study. V.T.H. received grants paid to the institute for studies outside the present work from AstraZeneca, Gilead, Novartis, Eli Lily, Pfizer, and Daiichi Sankyo. V.T.H. received consulting fees from Eli Lily outside the present work. M.G. received grants paid to the institute for studies outside the present work from Guerbet and Ferring. E.M.E.B. received a grant from The Dutch Network of Fertility Preservation for a study outside the present work. N/A.

Exploring the Interaction of Lipid Bilayers with Curcumin-Laponite Nanoparticles: Implications for Drug Delivery and Therapeutic Applications.

Curcumin, the active compound in turmeric, is renowned for its anti-inflammatory, antioxidant, and antimicrobial properties, making it beneficial for treating conditions like arthritis, neurodegenerative diseases, and various cancers. Despite its promising therapeutic potential, curcumin's poor bioavailability-due to its rapid metabolism and low solubility-limits its clinical efficacy. To address this, recent research has focused on enhancing curcumin delivery using nanoparticles, liposomes, and novel nanomaterials. Among these, laponite, a synthetic nanoclay, has shown promise in improving curcumin delivery due to its unique properties, including large surface area, dual charge, and stability in solution. This study explores the use of curcumin-laponite nanoparticles as carrier vehicles for controlled delivery to in vitro model membranes. Utilizing advanced techniques such as neutron reflectometry, atomic force microscopy, quartz crystal microbalance with dissipation, and infrared spectroscopy, the interaction between curcumin-laponite nanoparticles and solid-supported lipid bilayers is monitored, revealing enhanced stability and controlled release of curcumin across the membrane. These findings pave the way for the development of curcumin-based therapies targeting cardiovascular, neurological, and oncological diseases, leveraging the synergistic effects of curcumin's biological activity and laponite's delivery capabilities.