Search Results (7,582)

Background: Statins exhibit pleiotropic anti-inflammatory, antioxidant, and immunomodulatory effects, suggesting their potential in non-cardiovascular conditions. However, evidence supporting their repurposing remains limited, and off-label prescribing policies vary globally. Objective: To systematically review evidence on statin repurposing in oncology and infectious diseases, and to assess Hungarian regulatory practices regarding off-label statin use. Methods: A systematic literature search (PubMed, Web of Science, Scopus, ScienceDirect; 2010–May 2025) was conducted using the terms “drug repositioning” OR “off-label prescription” AND “statin” NOT “cardiovascular,” following PRISMA guidelines. Hungarian off-label usage data from the NNGYK (2008–2025) were also analyzed. Results: Out of 205 publications, 12 met the inclusion criteria—75% were oncology-focused, and 25% focused on infectious diseases. Most were preclinical (58%); only 25% offered strong clinical evidence. Applications included hematologic malignancies, solid tumors, Cryptococcus neoformans, SARS-CoV-2, and dengue virus. Mechanisms involved mevalonate pathway inhibition and modulation of host immune responses. Hungarian data revealed five approved off-label statin uses—three dermatologic and two pediatric metabolic—supported by the literature and requiring post-treatment reporting. Conclusions: While preclinical findings are promising, clinical validation of off-label statin use remains limited. Statins should be continued in cancer patients with cardiovascular indications, but initiation for other purposes should be trial-based. Future directions include biomarker-based personalization, regulatory harmonization, and cost-effectiveness studies. Full article

Pediatric high-grade glioma (pHGG) is a devastating group of childhood cancers associated with poor outcomes. Traditionally, diagnosis was based on histologic and immunohistochemical characteristics, including high mitotic activity, presence of necrosis, and presence of glial cell markers (e.g., GFAP). With advances in molecular tumor profiling, these tumors have been recategorized based on specific molecular findings that better lend themselves to prediction of treatment response and prognosis. pHGG is now categorized into four subtypes: H3K27-altered, H3G34-mutant, H3/IDH-WT, and infant-type high-grade glioma (iHGG). Molecular profiling has not only increased the specificity of diagnosis but also improved prognostication. Additionally, these molecular findings provide novel targets for individual tumor-directed therapy. While these therapies are largely still under investigation, continued investigation of distinct molecular markers in these tumors is imperative to extending event-free survival (EFS) and overall survival (OS) for patients with pHGG. Full article

Introduction: Although lipomas are common benign tumors found in adults, lipomas of the bladder are extremely rare. Bladder lipomas are infrequently reported in the urologic literature, with only 19 cases published worldwide. These can present as a mass on cystoscopy and cause irritative voiding symptoms, depending on their location. Upon transurethral resection, seeing fat can be concerning for a perforation, as lipoma can be mistaken for extravesical fat. Hence, familiarity with this rare entity is of paramount importance for urologists to prevent unnecessary investigations and interventions that are needed in case of a true bladder perforation. Case presentation: This study presents a case of bladder lipoma in a 73-year-old male with end-stage renal disease who presented for pretransplant urologic evaluation due to microscopic hematuria and irritative lower urinary tract symptoms (LUTS). During cystoscopy, a bladder mass was seen, and a transurethral resection of the bladder tumor (TURBT) revealed bright yellow adipose tissue immediately underneath the bladder mucosa. Concerns about perforation were obviated when seeing intact detrusor muscle underneath, visually confirming the integrity of the bladder wall. The resection was completed, and the CT scan was re-read with the radiologist, which confirmed the presence of a lipoma that was missed pre-operatively due to patient’s oliguria and collapsed bladder. No catheter drainage or cystogram was performed based on these findings. Outcome: The patient healed without any complications. Histopathology confirmed the diagnosis of a mature lipoma. The patient was cleared for transplant from a urologic standpoint and had a successful renal transplantation without delay. Discussion: This case documents the anomalous occurrence of a lipoma within the bladder and supports maintaining a broad differential, including liposarcoma, angiomyolipoma, and other non-malignant fatty tumors during the evaluation of a bladder mass. Full article

Background and clinical significance: Trichoblastomas are rare, mixed epithelial tumors with a mesenchymal component and hair follicle differentiation. Case presentation: Herein, we present a case report of a 51-year-old female patient presenting to the obstetrics and gynecology department with complaints of edema and erythema of the right Bartholin gland, and a lesion measuring 2 cm on the right lateral edge of the mons pubis, towards the inguinal fold. Marsupialization of the Bartholin gland was performed, as well as an incision into the pubo-inguinal lesion, which the patient depicted as grossly resembling an ingrown hair. Upon incision into the pubic–inguinal lesion, it was dark brown in color and spontaneously popped out of the subcutis, without an attempt at enucleation. Histology and subsequent immunohistochemistry of the lesion showed a blue basaloid tumor with an extensive pigment component located deep in the dermis that was sharply demarcated from the surrounding tissues. Conclusion: Immunohistochemistry was diffusely and strongly positive for epithelial markers; melanocytic markers were positive only in dendritic melanocytes dispersed within the tumors, and the proliferative index was low. As such, the tumor was identified as melanotrichoblastoma. Full article

Pancreatic neuroendocrine neoplasms (PNENs) are a diverse group of rare tumor subtypes, representing less than 2% of all pancreatic tumors. Often detected late in the clinical course, they are associated with high rates of morbidity and mortality. Hereditary syndromes such as multiple endocrine neoplasia type-1 and von Hippel–Lindau are associated with the development of PNENs, although only a small portion of total tumors have a genetic basis. This review aims to explore the recent advances in laboratory diagnostics, imaging modalities, medical management, and surgical approaches to hormone-producing PNENs (including some common, less common, and some rare subtypes), with the goal of assisting physicians in the integration of evidence-based information into their practice. Full article

Prostate cancer remains one of the most prevalent malignancies among men, and emerging evidence proposed a potential role for periprostatic adipose tissue (PPAT) in tumor progression. However, its relationship with imaging-based risk stratification systems such as PI-RADS remains uncertain. This retrospective observational study aimed to evaluate whether periprostatic and subcutaneous fat thickness are associated with PI-RADS scores or PSA levels in biopsy-naïve patients. We retrospectively reviewed 104 prostate MRI scans performed between January 2020 and January 2024. Fat thickness was measured on axial T2-weighted images, and statistical analyses were conducted using Spearman’s correlation and multiple linear regression. In addition to linear measurements, we also assessed periprostatic fat volume and posterior fat thickness derived from imaging data. No significant correlations were observed between fat thickness (either periprostatic or subcutaneous) and PI-RADS score or PSA values. Similarly, periprostatic fat volume showed only a weak, non-significant correlation with PI-RADS, while posterior fat thickness demonstrated a weak but statistically significant positive association. Additionally, subgroup comparisons between low-risk (PI-RADS < 4) and high-risk (PI-RADS ≥ 4) patients showed no meaningful differences in fat measurements. These findings suggest that simple linear fat thickness measurements may not enhance imaging-based risk assessment in prostate cancer, though regional and volumetric assessments could offer modest added value. Full article

Oxidative and glycolytic metabolism produce energy in the form of ATP and produce intermediates for biomass production. Oxidative metabolism predominates under normoxic conditions and in quiescent or slowly proliferating cells. On the other hand, under hypoxic or pseudohypoxic conditions and in rapidly proliferating cells, glycolysis becomes the predominant pathway. The balance between oxidative and glycolytic metabolism is finely tuned in physiological conditions and becomes dysregulated in many pathological conditions, most notably cancer. In this article we summarize the evidence that has been gathered over the last few years on the mechanisms underlying this balance and the consequences of their dysregulation. We discuss first the non-metabolic factors (mitochondria, cell cycle, cell type, tissue type), then molecules that are at the intersection between glycolytic and oxidative metabolism and those molecules that are inherent to oxidative or glycolytic metabolism that affect the equilibrium between the two energy-producing pathways. Eventually, we discuss pharmacologic or genetic means that allow manipulating this equilibrium. As will be seen, lactic acidosis has taken center stage in this field and lactate has been shown to fuel oxidative metabolism. This suggests that if glycolytic metabolism predominates, as has often been shown in cancer, mechanisms come into work that reestablish a metabolic heterogeneity. Thus, while one pathway may be predominant over the other, it seems as if fail-safe mechanisms are at work that avoid the possibility that it becomes the only energy-producing pathway. Eventually, we discuss possible therapeutic consequences that may derive from this expanding knowledge, in particular, as regards tumor therapy. Full article

Objectives: Circulating tumor DNA (ctDNA) has emerged as a reliable prognostic biomarker in both early- and late-stage non-small cell lung cancer (NSCLC) patients. However, its role in NSCLC with pleural dissemination (M1a), a subset of disease with indolent biology, remains to be elucidated. Methods: We collected 41 M1a patients with serial ctDNA and CEA monitoring. Progression-free survival (PFS) was assessed between patients with different levels of ctDNA and CEA. An independent cohort of 61 M1a patients was included for validation. Results: At the diagnostic landmark, the detection rates for ctDNA and CEA were 22% and 55%, respectively. Among patients who experienced disease progression with pleural metastases, only ten had detectable ctDNA in longitudinal timepoints, resulting in a sensitivity of 50%. Moreover, there was no significant difference in PFS between patients with longitudinally detectable and undetectable ctDNA (HR: 0.86, 95% CI 0.33–2.23, p = 0.76). In contrast, patients with a decreasing CEA trend within 3 months after diagnosis were associated with an improved PFS (HR: 0.22; 95% CI, 0.03–1.48, p = 0.004). This finding is confirmed in an independent M1a patient cohort. Conclusions: Together, our findings suggest that M1a NSCLC with isolated pleural dissemination may represent a “non-shedding” tumor type, where ctDNA shows limited diagnostic and prognostic value. Monitoring early changes in CEA could be a more cost-effective predictor of disease progression. Full article

Background: Postoperative recurrence of sacrococcygeal chordomas presents significant clinical challenges due to unusual recurrence patterns. This study aimed to characterize these patterns of recurrence to inform improved adjuvant radiotherapy planning. Methods: We retrospectively analyzed 31 patients with recurrent sacrococcygeal chordoma following surgery, assessing recurrence locations considering initial tumor extent, resection levels, and postoperative anatomical changes on MRI. In 18 patients, pre- and postoperative imaging enabled the spatial mapping of early recurrence origins relative to the initial tumor volume using isotropic expansions. The median initial gross tumor volume was 113 mL. Results: Recurrences were mostly multifocal and predominantly involved soft tissues (e.g., mesorectal/perirectal space (80.6%), piriformis and gluteal muscles (80.6% and 67.7%, respectively) and osseous structures, particularly the sacrum (87.1%)). The median time to recurrence was 15 months. The initial surgery was R0 in 17 patients (55%). The highest infiltrated sacral vertebra was S1 in 3%, S2 in 10%, S3 in 35%, S4 in 23%, S5 in 10%, and coccygeal in 19%. Anatomical changes post-resection, including rectal herniation into gluteal and subcutaneous tissues, significantly affected radiotherapy planning. Expansion of the initial tumor volume by 2 cm failed to encompass all recurrence origins in 72% of cases. A 5 cm expansion was required to achieve full coverage in 56% of patients, though 22% of recurrences still lay beyond this margin and the remaining were covered only partially. Conclusions: Recurrent sacrococcygeal chordomas exhibit complex, soft-tissue-dominant patterns and are influenced by significant anatomical displacement post-surgery. Standard target volume expansions are often insufficient to cover the predominantly multifocal recurrences. Full article

Background/Objectives: The 2019 WHO classification redefined high-grade gastrointestinal neuroendocrine neoplasms (GI NENs), encompassing not only poorly differentiated neuroendocrine carcinomas (NECs), but also well-differentiated grade 3 neuroendocrine tumors (NETs G3). Since both subtypes share a Ki-67 index > 20%, distinguishing them based solely on morphology is challenging. Prior studies have shown TP53 alterations in NECs but not in NETs. This study aimed to evaluate clinico-morphological parameters and the immunohistochemical (IHC) expression of p53 in high-grade GI NENs to identify relevant correlations. Methods: Tumors were stratified by Ki-67 index into two groups: >20–50% and >50%. p53 IHC expression was assessed as “wild-type” (1–20% positive tumor cells) or “non-wild-type” (absence or >20% positivity). Correlations were analyzed between Ki-67, p53 status, and various pathological features. Results: Significant correlations were found between the Ki-67 index and maximum tumor size, pT stage, lymphovascular invasion, perineural infiltration, and diagnostic classification. Similarly, p53 immunohistochemical status was significantly associated with lymphovascular invasion, lymph node metastasis, and tumor classification (NET G3 versus NEC, including NEC components of MiNENs). Conclusions: The findings support the value of Ki-67 and p53 as complementary biomarkers in the pathological evaluation of high-grade GI NENs. Their significant associations with key morphological parameters support their utility in differentiating NETs G3 from NECs, particularly in cases showing overlapping histological features. The immunohistochemical profile of p53 may serve as a useful diagnostic adjunct in routine practice. Full article

Background/Objectives: The heterogeneity of cancer disease and the frequent ineffectiveness and resistance observed with currently available treatments highlight the importance of developing new antitumor therapies. The properties of gold nanoparticles, such as their photon-energy heating, are attractive for oncology therapy; this can be effective and localized. The combination of chemotherapy and hyperthermia is promising. Our aim was to evaluate the combination therapy of photon hyperthermia with 5-fluorouracil (5-FU) both in vitro and in vivo. Methods: This study evaluated the antitumor efficacy of a combined chemo-photothermal therapy using 5-fluorouracil (5-FU) and branched gold nanoshells (BGNSs) in a colorectal cancer model. BGNSs were synthesized via a seed-mediated method and characterized by electron microscopy and UV–vis spectroscopy, revealing an average diameter of 126.3 nm and a plasmon resonance peak at 800 nm, suitable for near-infrared (NIR) photothermal applications. In vitro assays using SW620-GFP colon cancer cells demonstrated a ≥90% reduction in cell viability after 24 h of combined treatment with 5-FU and BGNS under NIR irradiation. In vivo, xenograft-bearing nude mice received weekly intratumoral administrations of the combined therapy for four weeks. The group treated with 5-FU + BGNS + NIR exhibited a final tumor volume of 0.4 mm³ on day 28, compared to 1010 mm³ in the control group, corresponding to a tumor growth inhibition (TGI) of 100.74% (p < 0.001), which indicates not only complete inhibition of tumor growth but also regression below the initial tumor volume. Thermographic imaging confirmed that localized hyperthermia reached 45 ± 0.5 °C at the tumor site. Results: These findings suggest that the combination of 5-FU and BGNS-mediated hyperthermia may offer a promising strategy for enhancing therapeutic outcomes in patients with colorectal cancer while potentially minimizing systemic toxicity. Conclusions: This study highlights the potential of integrating nanotechnology with conventional chemotherapy for more effective and targeted cancer treatment. Full article

Background: Tongue squamous cell carcinoma (TSCC) is an aggressive oral malignancy characterized by early submucosal invasion and a high risk of cervical lymph node metastasis. Accurate and timely diagnosis is essential, but it remains challenging when relying solely on conventional imaging and histopathology. This systematic review aimed to evaluate studies applying artificial intelligence (AI) in the diagnostic imaging of TSCC. Methods: This review was conducted under PRISMA 2020 guidelines and included studies from January 2020 to December 2024 that utilized AI in TSCC imaging. A total of 13 studies were included, employing AI models such as Convolutional Neural Networks (CNNs), Support Vector Machines (SVMs), and Random Forest (RF). Imaging modalities analyzed included MRI, CT, PET, ultrasound, histopathological whole-slide images (WSI), and endoscopic photographs. Results: Diagnostic performance was generally high, with area under the curve (AUC) values ranging from 0.717 to 0.991, sensitivity from 63.3% to 100%, and specificity from 70.0% to 96.7%. Several models demonstrated superior performance compared to expert clinicians, particularly in delineating tumor margins and estimating the depth of invasion (DOI). However, only one study conducted external validation, and most exhibited moderate risk of bias in patient selection or index test interpretation. Conclusions: AI-based diagnostic tools hold strong potential for enhancing TSCC detection, but future research must address external validation, standardization, and clinical integration to ensure their reliable and widespread adoption. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors, with a five-year overall survival rate below 10%. While the introduction of multi-agent chemotherapy regimens has improved outcomes marginally, most patients with advanced disease continue to have limited therapeutic options. Molecular profiling has uncovered actionable genomic alterations in select subgroups of PDAC, yet the clinical impact of targeted therapies remains modest. This review aims to provide a clinically oriented synthesis of emerging molecular targets in PDAC, their therapeutic relevance, and practical considerations for biomarker testing, including current FDA and EMA indications. Methods: A narrative review was conducted using data from PubMed, Embase, Scopus, and international guidelines (NCCN, ESMO, ASCO). The selection focused on evidence published between 2020 and 2025, highlighting molecularly defined PDAC subsets and the current status of targeted therapies. Results: Actionable genomic alterations in PDAC include KRAS G12C mutations, BRCA1/2 and PALB2-associated homologous recombination deficiency, MSI-H/dMMR status, and rare gene fusions involving NTRK, RET, and NRG1. While only a minority of patients are eligible for targeted treatments, early-phase trials and real-world data have shown promising results in these subgroups. Testing molecular profiling is increasingly standard in advanced PDAC. Conclusions: Despite the rarity of targetable mutations, systematic molecular profiling is critical in advanced PDAC to guide off-label therapy or clinical trial enrollment. A practical framework for identifying and acting on molecular targets is essential to bridge the gap between precision oncology and clinical management. Full article

Eukaryotic elongation factor 1A (eEF1A), the second most abundant intracellular protein, not only plays a key role in peptide elongation, but is also capable of numerous moonlighting functions. Within malignant cells, eEF1A is by no means a neutral bystander but instead actively participates in oncogenic transformations via a myriad of molecular pathways. Thus far, a broad range of small-molecule inhibitors have been identified, which, despite their structural diversity, suppress tumor growth by targeting eEF1A. Interestingly, just as eEF1A enables its oncogenic potential far beyond boosting protein translation, these targeted agents disrupt this oncoprotein via multiple axes distinct from mere protein synthesis inhibition. Whereas the oncogenic mechanisms of eEF1A has been well documented, there lacks a systemic survey of the eEF1A-targeting agents in terms of their mechanisms. Accordingly, the present work aims to examine their multifaceted modes of action more than just blocking protein synthesis. By unveiling these insights, our deepened knowledge of these eEF1A-binding inhibitors will inform the development of future eEF1A-targeted drugs for cancer treatment. Full article

Cancer is no longer considered as an isolated event. Rather, it occurs because of a complex biological drive orchestrating different cell types, growth factors, cytokines, and signaling pathways within the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are the most populous stromal cells within the complex ecosystem of TME, with significant heterogeneity and plasticity in origin and functional phenotypes. Very enigmatic cells, CAFs determine the progress and outcomes of tumors through extensive reciprocal signaling with different tumors infiltrating immune cells in the TME. In their biological drive, CAFs release numerous chemical mediators and utilize various signaling pathways to recruit and modulate tumor-infiltrating immune cells. The CAF-induced secretome and exosomes render immune cells ineffective for their antitumor activities. Moreover, by upregulating immune inhibitory checkpoints, CAFs create an immunosuppressive TME that impedes the susceptibility of tumor cells to tumor-infiltrating lymphocytes (TILs). Further, by depositing and remodeling extracellular matrix (ECM), CAFs reshape the TME, which enhances tumor growth, invasion, metastasis, and chemoresistance. Understanding of CAF biology and its crosstalk with tumor-infiltrating immune cells is crucial not only to gain insight in tumorigenesis but to optimize the potential of novel targeted immunotherapies for cancers. The complex relationships between CAFs and tumor-infiltrating immune cells remain unclear and need further study. Herein, in this narrative review we have focused on updates of CAF biology and its interactions with tumor-infiltrating immune cells in generating immunosuppressive TME and resistance to cell death. Full article