Search Results (41,400)

(1) Background: Pain is a common symptom in patients with Amyotrophic Lateral Sclerosis (ALS). There are no evidence-based pharmacological treatments for pain in ALS; recommendations are based on guidelines for chronic non-oncological pain and clinical experience. The aim is to map the literature on how people with ALS experience pain, and how this affects their daily activities and social relationships. (2) Methods: This scoping review included studies concerning patients with spinal/bulbar ALS aged ≥ 18 years who experience pain, focusing on perception, characteristics, treatment, and impact on quality of life. Temporal and linguistic criteria were applied when searching the MEDLINE, CINAHL, and SCOPUS databases. (3) Results: The management of pain in these patients is complex and involves the use of anti-inflammatory drugs, analgesics, and opioids. Pain is associated with other conditions such as depression and anxiety, which contribute to a deterioration in the quality of life. Moreover, pain may also negatively influence patient compliance with prescribed treatment regimens and the quality of care they perceive themselves to be receiving. (4) Conclusions: It is of the most importance to identify effective ways to assess and treat this issue, with health care professionals taking an active role in this process. Full article

Despite the considerable global burden of urologic malignancies, Low- and middle-income countries (LMICs) often encounter significant challenges in caring for patients with urologic malignancies. Several interrelated factors impact cancer care in LMICs, which face significant challenges that hinder effective diagnosis, treatment, and management of disease. Socioeconomic and healthcare infrastructure limitations are fundamental issues leading to the disparity observed in cancer care across the globe. This review aims to evaluate the challenges and disparities in access to comprehensive urologic care in LMICs, emphasizing the impact of such global disparities on incidence rates, timely diagnoses, and access to comprehensive care as it relates to prostate, kidney, and bladder cancers. Full article

All 189 World Bank member countries are classified by their capita gross national income into one of four income groups. In this review, we aim to explore the economic burden and management of urologic oncology conditions in low- and middle-income countries (LMICs), emphasizing disparities and challenges in treatment access. The current World Bank classification system highlights economic stratification, showing significant health outcome disparities, particularly in urologic oncology conditions including kidney, bladder, and prostate cancer. First, this review focuses on the management of advanced prostate cancer in Asian LMICs, revealing higher mortality-to-incidence ratios and a greater prevalence of metastatic disease compared to high-income countries (HICs). The prohibitive costs of novel hormonal therapies (NHTs) like abiraterone and enzalutamide limit their use and exacerbate outcome disparities. Second, we review Wilms tumor treatment with chemotherapy in African countries, noting significant price variations for adapted and non-adapted regimens across different economic settings. The cost of chemotherapy agents, particularly dactinomycin, acts as a primary driver of treatment expenses, underscoring the economic challenges in providing high-quality care. Lastly, bladder cancer treatment costs in Brazil and Middle Eastern countries are examined, highlighting how detrimental the economic burden of intravesical therapies, like mitomycin C and Bacillus Calmette–Guérin (BCG), is on treatment accessibility. Overall, this literature review emphasizes the financial strain on healthcare systems and patients, particularly in regions facing economic instability and drug shortages, and underscores the need for international cooperation and effective resource allocation to address the economic barriers to urologic care in LMICs, aiming to improve health outcomes and ensure equitable access to advanced treatments. Full article

We performed a literature review to identify articles regarding the state of urological cancers in low-to-middle-income countries (LMICs). The challenges that LMICs face are multifactorial and can include poor health education, inadequate screening, as well as limited access to treatment options and trained urologists. Many of the gold standard treatments in high-income countries (HICs) are scarce in LMICs due to their poor socioeconomic status, leading to an advanced stage of disease at diagnosis and, ultimately, a higher mortality rate. These standards of care are vital components of oncological disease management; however, the current and sparse literature available from LMICs indicates that there are many obstacles delaying early diagnosis and management options in LMICs. In the era of evolving medical diagnosis and treatments, sufficient data must be gathered and understood in order to provide appropriate diagnostic and treatment options to curtail rising mortality rates and, therefore, help to alleviate the burden in LMICs. Full article

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gut affecting both adults and children. Neutrophil extracellular traps (NETs) are structures released by activated neutrophils, potentially contributing to tissue damage in various diseases. This study aimed to explore the presence and role of NETs in pediatric IBD. We compared intestinal biopsies and peripheral blood from 20 pediatric IBD patients (UC and CD) to controls. Biopsy staining and techniques for neutrophil activation were used to assess neutrophil infiltration and NET formation. We also measured the enzymatic activity of key NET proteins and evaluated NET formation in UC patients in remission. Both UC and CD biopsies showed significantly higher levels of neutrophils and NETs compared to controls (p < 0.01), with UC exhibiting the strongest association. Peripheral blood neutrophils from UC patients at diagnosis displayed increased NET formation compared to controls and CD patients. Interestingly, NET formation normalized in UC patients following remission-inducing treatment. This pilot study suggests a potential role for NETs in pediatric IBD, particularly UC. These findings warrant further investigation into the mechanisms of NET involvement and the potential for targeting NET formation as a therapeutic strategy. Full article

RNA-binding proteins (RBPs) play critical roles in regulating post-transcriptional gene expression, managing processes such as mRNA splicing, stability, and translation. In normal intestine, RBPs maintain the tissue homeostasis, but when dysregulated, they can drive colorectal cancer (CRC) development and progression. Understanding the molecular mechanisms behind CRC is vital for developing novel therapeutic strategies, and RBPs are emerging as key players in this area. This review highlights the roles of several RBPs, including LIN28, IGF2BP1–3, Musashi, HuR, and CELF1, in CRC. These RBPs regulate key oncogenes and tumor suppressor genes by influencing mRNA stability and translation. While targeting RBPs poses challenges due to their complex interactions with mRNAs, recent advances in drug discovery have identified small molecule inhibitors that disrupt these interactions. These inhibitors, which target LIN28, IGF2BPs, Musashi, CELF1, and HuR, have shown promising results in preclinical studies. Their ability to modulate RBP activity presents a new therapeutic avenue for treating CRC. In conclusion, RBPs offer significant potential as therapeutic targets in CRC. Although technical challenges remain, ongoing research into the molecular mechanisms of RBPs and the development of selective, potent, and bioavailable inhibitors should lead to more effective treatments and improved outcomes in CRC. Full article

Methotrexate (MTX) is an anti-folate chemotherapeutic agent that is considered to be a gold standard in Acute Lymphoblastic Leukemia (ALL) therapy. Nevertheless, toxicities induced mainly due to high doses of MTX are still a challenge for clinical practice. MTX pharmacogenetics implicate various genes as predictors of MTX toxicity, especially those that participate in MTX intake like solute carrier family 19 member 1 (SLC19A1). The aim of the present study was to evaluate the association between SLC19A1 polymorphisms and its regulatory miRNAs with MTX toxicity in children with ALL. A total of 86 children with ALL were included in this study and were all genotyped for rs2838958, rs1051266 and rs1131596 SLC19A1 polymorphisms as well as the rs56292801 polymorphism of miR-5189. Patients were followed up (48, 72 and 96 h) after treatment with MTX in order to evaluate the presence of MTX-associated adverse events. Our results indicate that there is a statistically significant correlation between the rs1131596 SLC19A1 polymorphism and the development of MTX-induced hepatotoxicity (p = 0.03), but there is no significant association between any of the studied polymorphisms and mucositis or other side effects, such as nausea, emesis, diarrhea, neutropenia, skin rash and infections. In addition, when genotype TT of rs1131596 and genotype AA of rs56292801 are both present in a patient then there is a higher risk of developing severe hepatotoxicity (p = 0.0104). Full article

Background/Objectives: Although tyrosine kinase inhibitors (TKIs) targeting EGFR-activating mutations significantly improved the outcome of EGFR-mutant NSCLC, resistance inevitably emerges. Despite the heterogeneity of these resistance mechanisms, many induce activation of MAPK signaling in the presence of EGFR-TKIs. While ARAF gene amplification is identified as a resistance mechanism that activates MAPK signaling by directly interacting with RAS, little is known about its clinicopathologic characteristics. Methods: We conducted a single-center retrospective analysis of the presence of ARAF amplification in re-biopsied samples in patients with EGFR-mutant NSCLC resistant to EGFR-TKIs. Demographic data, treatment course, and clinical molecular testing reports were extracted from electronic medical records. ARAF amplification was determined using a gene copy number assay. RNA sequence analysis was performed in patients with ARAF amplification as well as presenting histologic transformations to small-cell lung carcinoma (SCLC). Results: ARAF amplification was identified in five of ninety-seven patients resistant to erlotinib or gefitinib, and four of forty-eight patients resistant to Osimertinib. ARAF amplification was dominantly observed in female patients with EGFR exon 19 deletion. All ARAF-amplified tumors retained their founder EGFR mutation and were absent of secondary mutations. Two cases were found where ARAF amplification correlated with a histological transformation to SCLC. Conclusions: ARAF amplification was identified in 5–8% of EGFR-TKI-resistant tumors. The possible roles of ARAF in SCLC transformation warrant further investigation. Full article

m⁶A modification is the most common internal modification of messenger RNA in eukaryotes, and the disorder of m⁶A can trigger cancer progression. The GGACU is considered the most frequent consensus sequence of target transcripts which have a GGAC m⁶A core motif. Newly identified m⁶A ‘readers’ insulin-like growth factor 2 mRNA-binding proteins modulate gene expression by binding to the m⁶A binding sites of target mRNAs, thereby affecting various cancer-related processes. The dynamic impact of the methylation at m⁶A within the GGAC motif on human IGF2BPs has not been investigated at the structural level. In this study, through in silico analysis, we mapped IGF2BPs binding sites for the GGm⁶AC RNA core motif of target mRNAs. Subsequent molecular dynamics simulation analysis at 400 ns revealed that only the KH4 domain of IGF2BP1, containing the 503GKGG506 motif and its periphery residues, was involved in the interaction with the GGm⁶AC backbone. Meanwhile, the methyl group of m⁶A is accommodated by a shallow hydrophobic cradle formed by hydrophobic residues. Interestingly, in IGF2BP2 and IGF2BP3 complexes, the RNA was observed to shift from the KH4 domain to the KH3 domain in the simulation at 400 ns, indicating a distinct dynamic behavior. This suggests a conformational stabilization upon binding, likely essential for the functional interactions involving the KH3-4 domains. These findings highlight the potential of targeting IGF2BPs’ interactions with m⁶A modifications for the development of novel oncological therapies. Full article

The virions of plant viruses and their structurally modified particles (SP) represent valuable platforms for recombinant vaccine epitopes and antitumor agents. The possibility of modifying their surface with biological compounds makes them a tool for developing medical biotechnology applications. Here, we applied a new type of SP derived from virions and virus-like particles (VLP) of Alternanthera mosaic virus (AltMV) and well-studied SP from Tobacco mosaic virus (TMV). We have tested the ability of SP from AltMV (AltMV SP_V) and TMV virions also as AltMV VLP to bind to and penetrate Ewing sarcoma cells. The adsorption properties of AltMV SP_V and TMV SP are greater than those of the SP from AltMV VLP. Compared to normal cells, AltMV SP_V adsorbed more effectively on patient-derived sarcoma cells, whereas TMV SP were more effective on the established sarcoma cells. The AltMV SP_V and TMV SP were captured by all sarcoma cell lines. In the established Ewing sarcoma cell line, the effectiveness of AltMV SP_V penetration was greater than that of TMV SP. The usage of structurally modified plant virus particles as a platform for drugs and delivery systems has significant potential in the development of anticancer agents. Full article

Background/Objectives: Determining how a patient with metastatic cancer is responding to therapy can be difficult for medical oncologists, especially with text-only radiology reports. In this investigation, we assess the clinical usefulness of a new algorithm-based analysis that provides spatial location and quantification for each detected lesion region of interest (ROI) and compare it to information included in radiology reports in the United States. Methods: Treatment response radiology reports for FDG PET/CT scans were retrospectively gathered from 228 patients with metastatic cancers. Each radiology report was assessed for the presence of both qualitative and quantitative information. A subset of patients (N = 103) was further analyzed using an algorithm-based service that provides the clinician with comprehensive quantitative information, including change over time, of all detected ROI with visualization of anatomical location. For each patient, three medical oncologists from different practices independently rated the usefulness of the additional analysis overall and in four subcategories. Results: In the 228 radiology reports, quantitative information of size and uptake was provided for at least one lesion at one time point in 78% (size) and 95% (uptake) of patients. This information was reported for both analyzed time points (current scan and previous comparator) in 52% (size) and 66% (uptake) of patients. Only 7% of reports quantified the total number of lesions, and none of the reports quantified changes in all lesions for patients with more than a few lesions. In the assessment of the augmentative algorithm-based analysis, the majority of oncologists rated it as overall useful for 98% of patients (101/103). Within specific categories of use, the majority of oncologists voted to use it for making decisions regarding systemic therapy in 97% of patients, for targeted therapy decisions in 72% of patients, for spatial location information in 96% of patients, and for patient education purposes in 93% of patients. Conclusions: For patients with metastatic cancer, the algorithm-based analysis of all ROI would allow oncologists to better understand treatment response and support their work to more precisely optimize the patient’s therapy. Full article

Purpose: The main objective of the study is to evaluate the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of naïve ovarian cancer women undergoing complete or near-complete cytoreduction by assessing the overall survival, the disease-specific survival, and the disease-free survival. The secondary objective is the identification of prognostic indicators of survival and recurrence of these patients. Patients—Methods: Retrospective study of treatment in naïve women with locally advanced ovarian cancer treated with cytoreductive surgery (CRS) and HIPEC and compared with those who were treated with cytoreduction alone. Clinicopathologic variables were correlated to overall survival, disease-specific survival, and disease-free survival using Kaplan–Meier method, and the multivariate Cox proportional hazards regression models. Results: 5- and 10-year overall survival, disease-specific survival, and disease-free survival rates were significantly higher in patients treated with CRS and HIPEC. These patients were 67% less likely to die from any cause (adjusted hazard ratio, aHR = 0.33, p = 0.001), 75% less likely to die from cancer (aHR = 0.25, p = 0.003), and 46% less likely to develop recurrence (aHR = 0.54, p = 0.041) compared to patients treated with CRS alone. Moreover, the poor performance status (aHR = 2.96, p < 0.001), the serous carcinomas (aHR = 0.14, p = 0.007), and the morbidity (aHR = 6.87, p < 0.001) were identified as independent indicators of poor overall survival. The degree of differentiation (aHR = 8.64, p = 0.003) was identified as the independent indicator of disease-specific survival (aHR = 4.13, p = 0.002), while the extent of peritoneal carcinomatosis (aHR = 2.32, p < 0.001) as the independent indicator of disease-free survival. Conclusions: Treatment in naïve patients with locally advanced ovarian cancer undergoing CRS plus HIPEC appears to have improved overall, disease-specific, and disease-free survival. Full article

Background: Ovarian cancer (OC) is the most prevalent gynecological malignancy in women, often diagnosed at an advanced stage due to the absence of specific clinical biomarkers. Notch signaling, particularly Notch3, is frequently activated in OC and contributes to its oncogenic role. Despite its known association with poor clinical outcomes, the biomarker potential of Notch3 remains inadequately explored. Methods: We investigated the biomarker potential of Notch3 in OC using multiple databases, including ONCOMINE, GEPIA, Human Protein Atlas, UALCAN, Kaplan–Meier Plotter, and LinkedOmics. We analyzed Notch3 expression levels, survival correlations, and clinicopathological parameters. Results: Notch3 expression was significantly upregulated in OC, as well as other cancers. Correlation analysis demonstrated that high Notch3 mRNA levels were associated with poor overall survival (OS) (p < 0.05) and relapse-free survival (p < 0.05) in OC patients. Human Protein Atlas data showed elevated Notch3 protein levels in OC tissues compared to healthy controls. Clinicopathological analysis indicated significant associations between Notch3 expression and patient age (p < 0.5), TP53 mutation status (p < 0.5), and cancer stage (p < 0.1). Additionally, genes such as WIZ, TET1, and CHD4 were found to be co-expressed with Notch3 in OC. Notch3 expression also correlated with immune cell infiltration in OC. Conclusions: Our bioinformatics analysis highlights Notch3 as a potential biomarker for poor prognosis in OC. However, further in vitro and in vivo studies, along with validation using larger tissue samples, are necessary to confirm its biomarker utility. Full article

Aim: To investigate the characteristics and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atz/Bev) who achieved a complete response (CR) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Methods: A total of 120 patients with Eastern Cooperative Oncology Group performance status (PS) 0 or 1 and Child–Pugh A at the start of Atz/Bev treatment were included. Barcelona Clinic Liver Cancer stage C was recorded in 59 patients. Results: The CR rate with Atz/Bev alone was 15.0%. The median time to CR was 3.4 months, and the median duration of CR was 15.6 months. A significant factor associated with achieving CR with Atz/Bev alone was an AFP ratio of 0.34 or less at 3 weeks. Adding transarterial chemoembolization (TACE) in the six patients who achieved a partial response increased the overall CR rate to 20%. Among the 24 patients who achieved CR, the median progression-free survival was 19.3 months, the median overall survival was not reached, and 14 patients (58.3%) were able to discontinue Atz/Bev and achieve a drug-free status. Twelve of these patients developed progressive disease (PD), but eleven successfully received post-PD treatments and responded well. Conclusions: Achieving CR by mRECIST using Atz/Bev alone or with additional TACE can be expected to offer an extremely favorable prognosis. Full article

Most studies on CTCs have focused on isolating cells that express EpCAM. In this study, we emphasize the presence of EpCAM-negative and EpCAM^low CTCs, in addition to EpCAM^high CTCs, in early BC. We evaluated stem cell markers (CD44/CD24 and CD133) and EMT markers (N-cadherin) in each subpopulation. Our findings indicate that all stemness variants were present in both EpCAM^high and EpCAM-negative CTCs, whereas only one variant of stemness (nonCD44+CD24−/CD133+) was observed among EpCAM^low CTCs. Nearly all EpCAM^high CTCs were represented by CD133+ stem cells. Notably, the hybrid EMT phenotype was more prevalent among EpCAM-negative CTCs. scRNA-seq of isolated CTCs and primary tumor partially confirmed this pattern. Therefore, further investigation is imperative to elucidate the prognostic significance of EpCAM-negative and EpCAM^low CTCs. Full article