Search Results (14,564)

Nucleic acid therapeutics are promising alternatives to conventional anti-cancer therapy, such as chemotherapy and radiation therapy. While conventional therapies have limitations, such as high side effects, low specificity, and drug resistance, nucleic acid therapeutics work at the gene level to eliminate the cause of the disease. Nucleic acid therapeutics treat diseases in various forms and using different mechanisms, including plasmid DNA (pDNA), small interfering RNA (siRNA), anti-microRNA (anti-miR), microRNA mimics (miRNA mimic), messenger RNA (mRNA), aptamer, catalytic nucleic acid (CNA), and CRISPR cas9 guide RNA (gRNA). In addition, nucleic acids have many advantages as nanomaterials, such as high biocompatibility, design flexibility, low immunogenicity, small size, relatively low price, and easy functionalization. Nucleic acid therapeutics can have a high therapeutic effect by being used in combination with various nucleic acid nanostructures, inorganic nanoparticles, lipid nanoparticles (LNPs), etc. to overcome low physiological stability and cell internalization efficiency. The field of nucleic acid therapeutics has advanced remarkably in recent decades, and as more and more nucleic acid therapeutics have been approved, they have already demonstrated their potential to treat diseases, including cancer. This review paper introduces the current status and recent advances in nucleic acid therapy for anti-cancer treatment and discusses the tasks and prospects ahead. Full article

Subependymal giant cell astrocytoma (SEGA) is most often found in patients with TSC (Tuberous Sclerosis Complex). Although it has been classified as a benign tumor, it may create a serious medical problem leading to grave consequences, including young patient demise. Surgery and chemotherapy belong to the gold standard of treatment. A broader pharmacological approach involves the ever-growing number of rapalogs and ATP-competitive inhibitors, as well as compounds targeting other kinases, such as dual PI3K/mTOR inhibitors and CK2 kinase inhibitors. Novel approaches may utilize noncoding RNA-based therapeutics and are extensively investigated to this end. The purpose of our review was to characterize SEGA and discuss the latest trends in the diagnosis and therapy of this disease. Full article

The routine use of granulocyte colony-stimulating factor (GCSF) is not recommended for the prevention or treatment of chemotherapy-induced neutropenia or febrile neutropenia because risks associated with certain types of cancers, distant organ metastases, and primary tumor growth cannot be excluded. We examined the association between GCSF use and the incidence of brain metastasis (BM), as well as BM-free survival (BMFS). This retrospective cohort study included 121 stage IV breast cancer patients without confirmed BM at the time of diagnosis and who received at least one course of systematic chemotherapy or target therapy at a tertiary teaching hospital between 1 January 2014 and 31 December 2022. The effect of GCSF use on BM was assessed with other confounding factors in Cox regression analyses. In this retrospective cohort, patients who received GCSF treatment had a significantly higher incidence of BM than those who did not (34.9% vs. 13.8%, p = 0.011). Univariate Cox regression analysis showed that GCSF use, menopause status, hormone treatment, HER2 treatment, cumulative dosage, dosage density, and neutropenia were independent risk factors for BMFS (p < 0.05). GCSF users had a higher risk of BM (adjusted HR: 2.538; 95% CI: 1.127–5.716, p = 0.025) than nonusers. BM risk was significantly associated with those with neutropenia (RR: 1.84, 95% CI: 1.21, 2.80) but not with those without neutropenia (RR: 0.59, 95% CI: 0.41–0.84, Interaction p-value < 0.05). The higher the dose density of GCSF, the higher the risk compared with those who do not use GCSF (p for trend < 0.01). These preliminary results suggest that GCSF is associated with BM in patients with stage IV breast cancer who did not have BM at initial diagnosis. Further comprehensively designed large-scale observational studies are needed to confirm our preliminary results. Full article

Resistance to chemotherapy is a problem of major social and economic importance, when looking at factors like the decrease in life expectancy, the associated therapeutic costs, and a significant number of cancers that resist current chemotherapy. The development of chemotherapeutics for all theoretically possible tumor variants is an approach that requires unreasonable resources. We propose a theoretical model that serves the purpose of overcoming resistance to chemotherapeutic agents used in cancer therapy. The model describes a gene delivery system based on liposomes, which are optically guided to the tumor’s location. The main aim of the gene delivery system is inhibiting the activity of enzymes involved in drug metabolism, hence offering the opportunity to use inexpensive chemotherapeutics that are already on the market. This model will reduce the costs of chemotherapy and will assure a positive outcome for patients. Full article

Objective: Heart failure affects 1–2% of the population in developed countries. Hemogram biomarkers are cheap, rapid, readily accessible and are known to have prognostic benefit in cardiovascular, infectious and oncologic diseases. Methods: The aim of the current study is to evaluate lymphocyte-to-white-blood-cell ratio (LWR) as a prognostic predictor in patients with heart failure. Patients with heart failure were recruited between January 2000 and July 2001. Exclusion criteria included metastatic malignancy, exposure to chemotherapy, radiotherapy or medications known to affect complete blood count. Results: 338 patients were enrolled, 33 were excluded. Mean age was 70.1 ± 10.8, 225 patients were male (73%) and 80 were female (27%). All patients were divided into three groups according to LWR. Group 1 < 0.2, group 2—0.2 < LWR < 0.35 and group 3 > 0.35. Patients with LWR ratio < 0.2 had the poorest survival while patients in the highest LWR (ratio > 0.35) had the best long-term survival. Conclusions: Patients with congestive heart failure and LWR < 0.2 showed significant increased mortality. LWR was shown as independent prognostic predictor for HF patients compared to other main outcome parameters, including CRP, NYHA, EF and LDL. Full article

Within the field of nanomedicine, which is revolutionizing cancer treatment, solid lipid nanoparticles (SLNs) have shown advantages over conventional chemotherapy when tested on cancer cells in preclinical studies. SLNs have proven to be an innovative strategy for the treatment of triple-negative breast cancer cells, providing greater efficiency than existing treatments in various studies. The encapsulation of antineoplastic drugs in SLNs has facilitated a sustained, controlled, and targeted release, which enhances therapeutic efficiency and reduces adverse effects. Moreover, the surface of SLNs can be modified to increase efficiency. For instance, the coating of these particles with polyethylene glycol (PEG) decreases their opsonization, resulting in a longer life in the circulatory system. The creation of positively charged cationic SLNs (cSLNs), achieved by the utilization of surfactants or ionic lipids with positively charged structural groups, increases their affinity for cell membranes and plasma proteins. Hyaluronic acid has been added to SLNs so that the distinct pH of tumor cells would stimulate the release of the drug and/or genetic material. The current review summarizes the recent research on SLNs, focusing on the encapsulation and transport of therapeutic agents with a cytotoxic effect on triple-negative breast cancer. Full article

Numerous scientific studies have been conducted in recent decades with the aim to study targeted application of zeolites in various industries, ecology, agronomy and medicine. The biggest advances, however, have been documented in medical and veterinary research of the natural zeolite, clinoptilolite. Although the exact biological mechanisms of action of the zeolite clinoptilolite are not completely elucidated, obtained results point to its antioxidative, immunomodulatory and detoxifying effects, the latter partially based on release of soluble and bioavailable silica forms from the surface material. The studied zeolite clinoptilolite materials have different geographical origins which confer to the physicochemical differences in the material. In addition, the production process of the material for oral applications differs between different producers which also accounts for different properties of the surface upon mechanical activation. Recently, a well-characterized zeolite clinoptilolite material, namely the PMA-zeolite, has been tested in different clinical applications and has shown potential as supportive therapy in inflammatory conditions, osteoporosis as well as during tumor chemotherapy. We accordingly present a comprehensive review of the PMA-zeolite effects in the clinical applications and discuss its probable mechanisms of effect in vivo. Full article

Background and rationale. Pleural mesothelioma (PM) is a rare and aggressive neoplasm that originates from the pleural mesothelium and whose onset is mainly linked to exposure to asbestos, which cannot be attacked with truly effective therapies with consequent poor prognosis. The rationale of this study is based on the use of mesenchymal stromal cells (MSCs) as a vehicle for chemotherapy drugs to be injected directly into the pathological site, such as the pleural cavity. Study design. The study involves the use of a conventional chemotherapeutic drug, Paclitaxel (PTX), which is widely used in the treatment of different types of solid tumors, including PM, although some limitations are related to pharmacokinetic aspects. The use of PTX-loaded MSCs to treat PM should provide several potential advantages over the systemically administered drug as reduced toxicity and increased concentration of active drug in the tumor-surrounding context. The PACLIMES trial explores the safety and toxicity of the local administration of Paclimes in chemonaive patients, candidates for pleurectomy. The secondary objective is to find the effective Paclimes dose for subsequent phase II studies and to observe and record the antitumor activity. Future direction. The experimental pre-clinical background and rationale are discussed as well. Full article

Abstract: Background/Objectives: Following the results of the phase 3 KEYNOTE-522 trial, the U.S. Food and Drug Administration approved pembrolizumab, a humanized IgG4 kappa monoclonal antibody, in combination with neoadjuvant chemotherapy as a new standard of care for high-risk early-stage triple-negative breast cancer (TNBC). This retrospective, multicenter study in Türkiye assessed the real-world efficacy and safety of neoadjuvant pembrolizumab combined with chemotherapy in early-stage TNBC. Methods: The study included 108 patients treated between 2021 and 2023 across 14 oncology centers. Three distinct neoadjuvant regimens incorporating pembrolizumab were administered at the discretion of the treating physicians. The primary outcomes were the pathological complete response (pCR) rate after neoadjuvant therapy and the 2-year event-free survival (EFS) and overall survival (OS) rates. Results: The observed pCR rate was 63.9%, closely mirroring the 64.8% reported in the KEYNOTE-522 trial. At the two-year mark, the EFS rate was 87.2% and the OS rate was 92.3%. Multivariable analysis identified pCR as the sole independent predictor of both EFS and OS. The safety profile was consistent with previous clinical trial data, with most adverse events being of grade 1−2 in severity. Conclusions: These findings provide valuable real-world confirmation of the efficacy and safety of neoadjuvant pembrolizumab–chemotherapy in early-stage TNBC, complementing evidence from randomized trials. Full article

Background: Brain metastases (BM) are a common, severe complication in patients with non-small cell lung cancer (NSCLC) and are difficult to treat due to their complex tumor biology and the intricate microenvironment of the brain. Objectives: This review examines the current role of immune checkpoint inhibitors (ICIs) in treating NSCLC with BM, focusing on the latest clinical trials, emerging strategies, current guidelines, and future directions. We highlight the efficacy of ICIs as monotherapy and in combination with other treatments such as radiotherapy, stereotactic radiosurgery, chemotherapy, and anti-VEGF agents. Results: While no single treatment sequence is universally accepted, combining ICIs with traditional therapies forms the core of the current treatment protocols. ICIs targeting the PD-1/PD-L1 pathway have significantly advanced NSCLC treatment, demonstrated by improved overall and progression-free survival in various settings. However, optimizing these benefits requires careful consideration of potential side effects, including cognitive decline and radiation necrosis, and the impact of steroid use on ICI efficacy. Conclusion: The review underscores the necessity for a personalized, integrated multidisciplinary treatment approach. Future research should focus on refining combination therapies and understanding the optimal sequence and timing of treatment. Full article

Objectives: To compare the clinical outcomes of intravenous carboplatin/paclitaxel chemotherapy plus bevacizumab versus intraperitoneal cisplatin/paclitaxel chemotherapy without bevacizumab as the frontline treatment in women with advanced ovarian, fallopian tube and primary peritoneal cancer. Methods: Between November 2012 and January 2024, medical records of all consecutive women with stage II~IV cancer treated with either frontline adjuvant intraperitoneal cisplatin/paclitaxel without bevacizumab (IP group), intravenous carboplatin/paclitaxel without bevacizumab (IV group) or intravenous carboplatin/paclitaxel with bevacizumab (IVB group) at a tertiary referral center were reviewed. Results: A total of 143 women (IP group, n = 57; IVB group, n = 23; IV group, n = 63) were reviewed. The IP group had greater progression-free survival compared to the IVB group (49.1 months, 95% confidence interval [CI] = 27.8 months to infinity, versus 11.9 months, 95% CI = 11.2 to 16.2 months; adjusted hazard ratio [HR] = 0.45, 95% CI = 0.24 to 0.87, p = 0.017). Additionally, the IP group also had a higher overall survival compared to the IVB group (not reached, 95% CI = 55.6 months to infinity, versus 38.9 months, 95% CI = 21.9 months to infinity; adjusted HR = 0.34, 95% CI = 0.15 to 0.79, p = 0.012). Conclusions: Intraperitoneal cisplatin/paclitaxel chemotherapy without bevacizumab seems to offer a survival advantage when compared with intravenous carboplatin/paclitaxel with bevacizumab in the frontline treatment of women with advanced ovarian cancer. Full article

Objective: Adenoid cystic carcinoma (ACC) is a rare malignant tumor that mainly arises in the head and neck area. We aimed to compare the long-term survival of patients with ACC based on their geographic regions within the United States using the Surveillance, Epidemiology, and End Results (SEER) registry data. Methods: We queried the SEER database to evaluate the geographic distribution of ACC patients based on inpatient admissions. The states included in the study were divided into four geographical regions (Midwest, Northeast, South, and West) based on the U.S. Census Bureau-designated regions and divisions. Demographic and clinical variables were compared between the groups. Kaplan–Meier curves and Cox regression were used to assess late mortality. Results: A total of 5150 patients were included (4.2% from the Midwest, 17.2% from the Northeast, 22.5% from the South, and 56.1% from the West regions). The median follow-up was 12.3 (95% CI: 11.6–13.1 years). Median overall survival was 11.0 (95% CI: 9.2-NR years), 14.3 (95% CI: 12.4–16.4 years), 11.3 (95% CI: 9.7–14.8 years), and 12.0 (95% CI: 11.3–13.0 years) for Midwest, Northeast, South, and West regions, respectively. In multivariable analysis, older age, male sex, thoracic cancer, the presence of regional and distal disease, receiving chemotherapy, not undergoing surgical resection, and being treated in the West vs. Northeast region were found to be independent predictors of poor survival. We identified a significant survival difference between the different regions, with the West exhibiting the worst survival compared to the Northeast region. Conclusions: In addition to the well-known predictors of late mortality in ACC (tumor location, stage, and treatment modalities), our study identified a lack of social support (being unmarried) and geographic location (West region) as independent predictors of late mortality in multivariable analysis. Further research is needed to explore the causal relationships. Full article

As the incidence of colorectal cancer (CRC) increases among younger adults, the need for discussions regarding treatment-related infertility is growing. The negative impacts of gonadotoxic chemotherapy and pelvic radiation are well documented, but the role that surgical intervention for CRC plays in infertility is less clear. Additionally, treatment-related infertility counseling occurs infrequently. This review provides an overview of the connection between abdominal and pelvic surgery on male and female infertility and elucidates the role of surgeons in counseling to alleviate psychological distress in newly diagnosed patients. A review of the literature revealed that pelvic surgery leads to increased adhesion formation, which is known to be associated with female infertility. Furthermore, nerve damage from pelvic surgery has significant implications for ejaculatory issues in males and sexual dysfunction in both males and females, which ultimately impact pregnancy success. Patients have significant distress related to treatment-related infertility, and pre-treatment fertility counseling has been shown to alleviate some of this psychological burden. Nevertheless, many patients do not receive counseling, particularly in surgical clinics, despite surgeons often being the first providers to see newly diagnosed non-metastatic patients. Efforts should be made to enact protocols that ensure fertility conversations are being had with patients in surgical clinics and that patients are being referred to fertility specialists appropriately. This patient-centered approach will lessen the psychological burden placed on patients during a vulnerable time in their lives. Full article

Extra-skeletal Ewing sarcoma (EWS) occurs in about 12% of EWS patients; at the same time, primary involvement of the kidneys remains extremely rare. Since it was first described in 1975, only a small case series have been reported worldwide. About 95% of surgically treated patients with EWS of the kidney described in the literature underwent nephrectomy, and the remaining patients only had a tumor biopsy. Nephron-sparing surgery (NSS) has not been sufficiently investigated as an alternative in the local surgical treatment of localized disease, mostly as a result of technically unfeasible provisions of negative surgical margins. In this report, we present a unique case of primary EWS of the kidney with an asymptomatic course without radiographic signs that suggest a highly aggressive disease, successfully locally treated with robotic-assisted NSS. This report showcases that robotic-assisted NSS could be a feasible alternative in treatment of localized disease yielding equally good oncological results while, at the same time, creating better prerequisites for necessary adjuvant chemotherapy. Full article

Gangliosides are glycosphingolipids composed of a sialylated glycan head group and a ceramide backbone. These anionic lipids form lipid rafts and play crucial roles in regulating various proteins involved in signal transduction, adhesion, and cell–cell recognition. Neuroblastoma, a pediatric cancer of the sympathetic nervous system, is treated with intensive chemotherapy, radiation, and an antibody targeting the GD2 ganglioside. Gangliosides are critical in neuroblastoma development and serve as therapeutic targets, making it essential to establish a reliable, rapid, and cost-effective method for profiling gangliosides, particularly one capable of isomeric separation of intact species. In this study, liquid chromatography–mass spectrometry (LC-MS) was optimized using standard gangliosides, followed by the optimization of sphingolipid extraction methods from cell lines by comparing Folch and absolute methanol extraction techniques. Percent recovery and the number of identified sphingolipids were used to evaluate the analytical merits of these methods. A standard gangliosides calibration curve demonstrated excellent linearity (R² = 0.9961–0.9975). The ZIC-HILIC column provided the best separation of ganglioside GD1 isomers with a 25 min runtime. GD1a elutes before GD1b on the ZIC-HILIC column. Absolute methanol yielded better percent recovery (96 ± 7) and identified 121 different sphingolipids, the highest number between the two extraction methods. The optimized method was applied to profile gangliosides in neuroblastoma (COG-N-683), pancreatic cancer (PSN1), breast cancer (MDA-MB-231BR), and brain tumor (CRL-1620) cell lines. The ganglioside profile of the neuroblastoma cell line COG-N-683 showed an inverse relationship between GD1 and GD2. Ceramide, Hex1Cer, GM1, and GM3 were highly abundant in CRL-1620, PSN1, and MDA-MB-231BR, respectively. These results suggest that our method provides a sensitive, reliable, and high-throughput workflow for ganglioside profiling across different cell types. Full article