Search Results (1,020)

Background: Previous studies mainly investigated singular serum tumor marker (STM) measurements for the management of advanced cancer patients, resulting in differences between recommended cut-off points and associated accuracies in evaluating treatment outcomes. We aimed to determine which STM dynamics recur during treatment in advanced non-small cell lung cancer (NSCLC) patients with disease control three months after starting with immune checkpoint inhibitor (ICI)-containing treatment and explore whether these dynamics retain information on treatment outcomes. Methods: This real-world exploratory multi-center observational cohort study included advanced NSCLC patients with clinical and radiological disease control three months after starting with ICI-containing treatment and at least three STM measurements for at least one STM during treatment. STM dynamics visualized for all patients were subclassified into three serological response patterns by two investigators who were blinded for treatment outcomes. Results: Between March 2013 and January 2023, 256 patients were included at two thoracic oncology outpatient clinics in The Netherlands. Kaplan–Meier survival analyses showed a significant association between the serological response patterns and both progression-free survival (PFS) and overall survival (OS). Additionally, the serological response patterns could be used to distinguish a durable response versus secondary treatment resistance, and oligoprogression versus systemic progression. Conclusions: Our findings underscore the value of monitoring STM dynamics in advanced NSCLC patients during ICI-containing treatment to improve response classification and decision-making in clinical practice. Future studies should explore the value of the identified dynamics in other tumor- and systemic treatment-types and tumor cell analytes for assessing treatment outcomes across multiple indications. Full article

Background: Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. While early-stage disease has favorable outcomes, advanced or recurrent EC remains associated with poor prognosis. Novel prognostic markers are needed to refine risk stratification. Systemic inflammation-based indices such as Pan-Immune Inflammation Value (PIV), Systemic Inflammation Response Index (SIRI), and Systemic Immune Inflammation Index (SII) have shown prognostic potential in solid tumors. Methods: We retrospectively evaluated 78 patients with endometrioid EC who had undergone hysterectomy with adnexectomy and lymphadenectomy. Demographic, clinicopathological, and laboratory data were extracted from electronic medical records. PIV, SII, and SIRI were calculated from the preoperative complete blood counts. Survival was assessed using Kaplan–Meier analysis, while prognostic factors were determined using univariate and multivariate Cox regression analyses. Results: The median age was 59 years, and 64.1% of the patients presented with early-stage disease. A high PIV (≥802) was significantly associated with a shorter overall survival (64 vs. 111 months, p < 0.001). PIV demonstrated the highest discriminatory accuracy (AUC = 0.776), followed by the SII (0.747) and SIRI (0.718). Univariate analysis identified that age, grade, LVSI, PNI, stage, distant metastasis, and high PIV, SII, SIRI, and NLR were predictors of poor survival. Multivariate analysis confirmed grade, distant metastasis and SIRI ≥ 1.5 as independent prognostic factors. Conclusions: Inflammation-based indices, particularly PIV and SIRI, correlated with survival outcomes in patients with EC. The SIRI retained an independent prognostic value, whereas PIV showed a strong discriminatory capacity. Incorporating these indices into established risk models may improve prognostic precision and support individualized management. Full article

Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those of European or Asian descent. Identifying microRNA (miRNA) signatures that contribute to these disparities may enhance prognostic accuracy and inform personalized therapeutic strategies. Methods: In this study, we identified prognostic markers of overall survival in serous ovarian cancer (SOC) using data from The Cancer Genome Atlas (TCGA) and the Human Protein Atlas. Integrative bioinformatic analyses revealed three key prognostic genes—TIMP3 (Tissue Inhibitor of Metalloproteinases-3), BRAF (v-raf murine sarcoma viral oncogene homolog B), and ITGB1 (Integrin Beta-1)—as critical molecular determinants associated with survival in patients with SOC. Candidate miRNAs regulating these genes were predicted using TargetScanHuman v8.0, identifying a core regulatory set comprising miR-192, miR-30d, miR-16-5p, miR-143-3p, and miR-20a-5p. To validate their clinical relevance, formalin-fixed, paraffin-embedded (FFPE) and fresh SOC tumor samples were obtained from African American and Caucasian patients who underwent surgery at Loma Linda University (LLU) between 2010 and 2023. Results and Discussion: Among all these, ITGB1 (p = 0.00033), TIMP3 (p = 0.0035), and BRAF (p = 0.026) emerged as statistically significant predictors. Following total RNA extraction, cDNA synthesis, and quantitative reverse transcription PCR (qRT-PCR), the expression levels of these miRNAs and their target genes were quantified. In the LLU cohort, ITGB1 and TIMP3 were significantly upregulated in African American patients compared to Caucasian patients (p < 0.01 and p < 0.02, respectively). Among the miRNAs, miR-192-5p was particularly noteworthy, showing marginally differential expression in LLU samples (p = 0.0712) but strong statistical significance in the TCGA cohort (p = 0.00013), where elevated expression correlated with poorer overall survival (p = 0.021). Pathway enrichment and gene ontology analyses (miRTargetLink2.0, Enrichr) revealed interconnected regulatory networks linking miR-192, miR-16-5p, miR-143-3p, and miR-20a-5p to ITGB1; miR-143-3p/miR-145-5p to BRAF; and miR-16-5p and miR-30c/d to TIMP3. Conclusions: Collectively, these findings identify distinct miRNA–mRNA regulatory signatures—particularly the miR-192-5p–ITGB1/TIMP3 axis—as potential clinically relevant biomarkers that may contribute to racial disparities and disease progression in ovarian cancer. Full article

Background: Sepsis is a leading cause of mortality in intensive care units, with liver dysfunction representing a critical determinant of poor outcome, mainly associated with excessive inflammation and oxidative stress. Lycopene, a carotenoid with potent antioxidant and anti-inflammatory properties, has been proposed as a potential therapeutic agent. This study investigated whether lycopene supplementation mitigates lipopolysaccharide-induced oxidative and inflammatory liver injury in rats. Methods: Male Wistar rats, divided into four groups, were exposed to either lipopolysaccharide or a combination of lipopolysaccharide (10 mg/kg) and lycopene (6 mg/kg). In order to assess liver damage induced by lipopolysaccharide, hepatocellular injury markers, oxidative stress indices, nitric oxide metabolism, glutathione redox status, apoptotic enzyme activity, and inflammatory mediators were assessed in serum and liver tissue. Results: Lipopolysaccharide induced marked hepatocellular damage, characterized by elevated serum liver-cell damage parameters, and liver tissue xanthine oxidase, myeloperoxidase, thiobrabituric reactive substances, protein carbonyl content, deoxyribonuclease I/II activity, nuclear factor kappa B, tumor necrosis factor-α, and interleukin-6, alongside depletion of reduced glutathione and reduced glutathione reductase and glutathione peroxidase activities. Lyc pretreatment significantly attenuated liver enzyme leakage, oxidative damage, and cytokine release while restoring reduced glutathione and glutathione reductase activity. In contrast, lycopene had limited effects on glutathione peroxidase activity, nitric oxide/inducible nitric oxide synthase signaling, and nuclear factor erythroid 2-related factor 2 expression. Conclusions: These findings demonstrate that lycopene confers partial hepatoprotection in endotoxemic rats, primarily through suppression of oxidative damage and nuclear factor kappa B-mediated inflammation. Further studies are needed to clarify tissue-specific mechanisms and optimize dosing strategies in order to increase the efficacy of this carotenoid. Full article

Background: The E26 transformation-specific (ETS) transcription factor Friend Leukemia Integration 1 (FLI1) has been linked to breast cancer aggressiveness, stromal remodeling, and immune modulation, yet the regulatory mechanisms governing its activity remain poorly defined. Of note, various studies have shown that EWS-FLI1-mediated transcription programs are facilitated via direct recruitment and binding of the NuRD-LSD1 complex, regulating its associated gene targets. Furthermore, LSD1 inhibition exhibited reverse transcriptional profiles driven by ETS-FLI and reduced in vivo tumorigenesis in cancers. Methods: We evaluated FLI1 expression across multiple invasive breast carcinoma (IBC) cohorts to determine its prognostic significance and associations with stromal features. In parallel, we investigated FLI1 regulation in humanized breast cancer mouse models treated with an LSD1 inhibitor. Results: High FLI1 expression was associated with advanced histological grade in IBC, consistent with an oncogenic function. FLI1-high tumors also exhibited elevated stromal and immune scores, indicating a role in remodeling the tumor microenvironment. Additionally, LSD1 inhibition downregulated FLI1 target genes involving angiogenesis and invasion. Conclusions: These findings highlight the dual role of FLI1: tumor-intrinsic FLI1 promotes proliferation and invasion, whereas its transcriptional regulation in tumor and endothelial compartments likely reflects LSD1 dependence. Collectively, our results support a mechanistic model in which LSD1–FLI1 crosstalk is involved in immune and stromal remodeling, positioning FLI1 as both a marker of tumor aggressiveness and a potential predictor of response to epigenetic therapies in breast cancer. Full article

Background/Objectives: Juzentaihoto (JTT), a traditional Kampo formula composed of ten medicinal herbs, is widely prescribed in Japan for immune enhancement and general health maintenance. This exploratory, open-label pilot study aimed to evaluate the feasibility and immunomodulatory effects of JTT in cancer patients and to explore its potential mechanisms of action. Methods: Ten cancer patients received oral JTT (7.5 g/day) for 14 days, while healthy volunteers served as a reference group. Peripheral natural killer (NK) cell phenotypes and CD95 expression were analyzed by flow cytometry, and serum Fas ligand (FasL) concentrations were measured by ELISA. Complementary in vitro assays using PBS-extracted, autoclaved JTT were conducted to assess Fas/FasL-mediated apoptosis in Jurkat and primary T cells by flow cytometry and Western blotting for cleaved caspase-8 and -3. Additional experiments with staurosporine (intrinsic apoptosis) and TRAIL in OSC-19 carcinoma cells were performed to determine pathway specificity. Results: In patients, most NK-cell markers showed no statistically significant within-subject changes, although a trend-level increase in NKp46 and a significant reduction in NK-cell CD95 expression (paired p = 0.014) were observed. Between-group differences primarily reflected baseline disparities between cancer patients and healthy controls. In vitro, JTT (50–100 µg/mL) partially attenuated FasL-induced apoptosis and reduced cleaved caspase-3 without affecting cleaved caspase-8, suggesting selective downstream modulation of the extrinsic pathway. Conclusions: Within the limitations of a small, non-randomized cohort without placebo, these findings are hypothesis-generating and indicate that JTT selectively modulates Fas-mediated lymphocyte apoptosis without promoting tumor immune evasion. Further randomized trials and mechanistic studies incorporating co-culture or 3D tumor–immune models are warranted to confirm these observations and identify active constituents. Full article

Background: Oxidative stress represents a key pathogenic factor in spondyloarthritis (SpA), yet its comprehensive assessment remains underutilized in routine clinical practice. Objectives: We evaluated oxidative stress biomarker profiles in SpA patients to determine associations with disease activity, systemic inflammation, structural damage, lifestyle factors, and therapeutic responses for practical clinical implementation. Methods: This cross-sectional study included 101 patients meeting the Assessment of SpondyloArthritis International Society (ASAS) 2009 criteria. Oxidative stress assessment utilized a validated biomarker panel: copper, zinc, glutathione peroxidase (GPx), ceruloplasmin (Cp), transferrin (TF), haptoglobin (Hp), bilirubin (BR), and uric acid (UA). Clinical, radiological, lifestyle, and therapeutic data underwent systematic analysis. Results: Glutathione peroxidase activity was elevated in 82.1% of patients, establishing it as the most sensitive oxidative stress marker. Copper levels increased in 30.7% and zinc deficiency occurred in 36.4% of cases. Oxidative stress markers correlated significantly with inflammatory parameters (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], neutrophil-to-monocyte ratio [NMR], systemic immune-inflammation index [SII]) and disease activity scores (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score based on CRP [ASDAS-CRP], Disease Activity Score 44 [DAS44-CRP]). Higher oxidative stress was associated with a poorer quality of life, as indicated by elevated Ankylosing Spondylitis Quality of Life (ASQoL) scores. Physical activity and adherence to a Mediterranean diet were independently associated with better antioxidant capacity. Smoking and nonsteroidal anti-inflammatory drug (NSAID) use correlated with increased oxidative burden. Anti-tumor necrosis factor alpha (anti-TNFα) therapy was associated with reduced levels of oxidative stress. Structural damage, particularly cervical spine involvement, correlated with heightened oxidative stress. Conclusions: This comprehensive evaluation reveals significant clinical correlations between oxidative stress and multiple disease domains in SpA. Modifiable lifestyle factors and therapeutic interventions have a significant impact on the redox balance. These findings establish practical targets for personalized management. The integration of oxidative stress assessment into routine practice could enhance disease monitoring and inform the development of antioxidant-based therapeutic strategies. Full article

Hormonal alterations associated with polycystic ovary syndrome (PCOS) also impact bone metabolism, though it is unclear if this is bone-protective or not. Bone marker dysfunction has been reported in PCOS and appears to be associated with obesity. This study sought to determine whether a panel of bone marker proteins (BMPs) would be dysregulated in PCOS stratified by BMI as a potential biomarker for bone in PCOS. In this exploratory cross-sectional study, plasma was collected from 234 women (137 with PCOS and 97 controls) from a biobank cohort and compared to a nonobese, non-insulin resistant population (24 with PCOS and 24 controls). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for the following BMPs: sclerostin; Dickkopf-related protein-1; glycogen synthase kinase-3 alpha/beta; periostin; tumor necrosis factor ligand superfamily member 11; fibroblast growth factor 23; sphingosine kinase 1; sphingosine kinase 2; cathepsins A, B, D, E, G, L2, S and Z; parathyroid hormone; osteocalcin; tumor necrosis factor ligand superfamily member 11 (sRANKL) and interleukin-1 beta. Four BMPs differed in the PCOS cohort (whole set without matching for body mass index (BMI) or insulin resistance (IR)): periostin (p = 0.05), cathepsin L (p = 0.05) and osteocalcin (p = 0.02) decreased in PCOS, whilst cathepsin D (p = 0.02) increased; however, linear regression showed that only cathepsins D and L and osteocalcin differed. None of the BMPs differed in the nonobese women with and without PCOS, nor in obese PCOS and controls stratified by BMI greater than 30 kg/m². In subgroup analysis, periostin (p = 0.001), sphingosine kinase 2 (p = 0.01) and cathepsin L (p = 0.001) were higher in obese versus nonobese PCOS (p = 0.01). Cathepsin Z (p = 0.02), sphingosine kinase 2 (p = 0.04) and lysosomal protective protein (p = 0.05) were lower in obese versus nonobese controls. Changes in BMPs indicative of impaired bone physiology were associated with BMI in both controls and PCOS, but did not differ between women with and without PCOS when BMI was matched. Hyperandrogenemia in PCOS did not affect BMP levels. Full article

Virotherapy is a promising method for treating oncological diseases, including such aggressive and difficult-to-treat brain tumors such as glioblastoma. Recombinant vaccinia virus VV-GMCSF-Lact has previously shown high antitumor potential against tumor cells of varying histogenesis, including gliomas, and completed a Phase I clinical trial, demonstrating safety and good tolerability in patients with recurrent/refractory metastatic breast cancer. Investigating two types of VV-GMCSF-Lact delivery, intravenous and intratumoral, into orthotopically transplanted C6 glioma in rats, it was shown that intratumoral injection significantly increases tumor volumes in comparison with intravenous virus delivery and is accompanied by noticeable toxic effects. Extensive areas of necrotic decay of tumor tissue and its significant mixed-cell infiltration and peritumoral edema, affecting the tumor volume, were detected using H&E staining of C6 tumors after intratumoral injection of VV-GMCSF-Lact. However, only with intratumoral administration was a significant decrease in the level of the tumor cell proliferation marker Ki67 demonstrated by immunohistochemical staining. The observed toxic effects of VV-GMCSF-Lact with intratumoral administration revealed the need for dose selection, which was performed on a mouse GL261 glioma model. Results of the study allowed us to determine the viral dose that does not lead to toxic effects and can potentially increase life expectancy of mice. The data obtained show the need for careful selection of both the route of viral drug dose and administration. Full article

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths among individuals over the age of 50. It is characterized by exceptional aggressiveness and is often diagnosed at an advanced stage, highlighting the importance of assessing prognostic factors. The deep awareness of these factors may help in better prevention and treatment planning, eventually improving the outcomes. Favorable prognostic factors include female gender, low tumor stage, ECOG (Eastern Cooperative Oncology Group) 0–1, lowest ASI (Activated Stroma Index), low-grade tumor budding, age below 40, adequate nutrition, and absence of distant metastases. Conversely, unfavorable prognostic factors include the presence of distant metastases and metastases into lymph nodes, high tumor stage, LVI (lymphovascular invasion), PNI (perineural invasion), tumor size above 3 cm, invasion into vessels, higher G grade, higher ASI, high-grade tumor budding, more than 1 CTC (circulating tumor cells) in the bloodstream, ECOG 3–4, age above 40, Black ethnicity, malnutrition, and sarcopenia. This review discusses the prognostic factors of PDAC related to tumor characteristics and the patient’s clinical issues. The aim of this review is to synthesize current evidence on prognostic determinants in PDAC, with particular attention to both tumor characteristics and patient-specific clinical features. To achieve this, a comprehensive literature review was performed using PubMed, BrowZine Library, Cochrane Library, SpringerLink, Wiley Online Library, BMJ Journals, and Google Scholar. Relevant studies addressing established and emerging prognostic markers were critically analyzed to provide an updated overview of factors that may influence survival and treatment outcomes. By integrating available data, this review seeks not only to summarize classical prognostic variables but also to highlight novel and underrecognized markers that may hold future clinical relevance. Such an approach may contribute to the refinement of prognostic models, support more accurate patient counseling, and ultimately aid in the optimization of therapeutic strategies for individuals affected by PDAC. Full article

For patients with metastatic uveal melanoma (UM), tebentafusp is currently the only systemic therapy approved by the EMA and FDA, but its use is limited to HLA-A*02:01-positive individuals. Immune checkpoint blockade (ICB) represents another option, though only a small subgroup of patients benefits, and no reliable predictive biomarkers are available to date. The aim of this study was therefore to identify parameters associated with favorable ICB response. Tumor samples and clinical data from 30 patients were analyzed. Group A (n = 16) showed clinical benefit, while Group B (n = 14) experienced disease progression. NanoString^® analyses revealed 258 upregulated genes in Group A, including IDO1, CD28, and CCL8. The enriched pathways were predominantly linked to immune activation, leukocyte adhesion, and responses to external stimuli. Immunohistochemistry confirmed significantly higher CD28 expression on infiltrating immune cells in Group A, while a machine learning approach identified CCL8 as a predictive marker with ~78% accuracy. Overall survival differed significantly between the groups. These findings indicate that patients responding to ICB display tumors with enhanced immune activation. CD28 and CCL8 emerged as promising candidates and should be validated in prospective studies to determine their clinical utility. Full article

Background and Clinical Significance: In gastric cancer, splenic metastases are found in less than 7% of cases and are usually associated with other systemic secondary determinations; much more rarely, they represent the sole secondary determination of the malignant disease. Case presentation: In this paper, we present the case of a 64-year-old patient who underwent curative surgery for gastric adenocarcinoma 10 months ago and, during oncological monitoring, was diagnosed with a splenic tumor formation with intense metabolic activity on PET-CT examination, raising suspicion of splenic metastases. The medical team observed an increase in carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and Cluster of Differentiation (CD) 276 values, along with a slight decrease in Dickkopf Related Protein 3 (DKK 3). Considering that the spleen was the only site of secondary localization of the malignant disease, the patient underwent laparoscopic splenectomy with histopathological confirmation of the presence of gastric adenocarcinoma. There are no signs of loco-regional or distant recurrence 15 months postoperatively. In patients with radical excision of gastric cancer who present only with splenic metastases, splenectomy is indicated and is associated with good disease-free survival. If other secondary manifestations of malignant gastric disease are identified or suspected, chemotherapy treatment and the wait-and-see approach are recommended, as the patient does not have a real benefit from splenectomy. Until now, there is no standard protocol for the diagnostic and therapeutic management of patients with gastric cancer and metachronous splenic metastases; thus, the development of a decision-making scheme for these situations is necessary. Conclusions: The multidisciplinary approach, including the tumor board and an infectious disease specialist, are important steps in the effective management of these cases. The role of new biological markers such as CD 276 and DKK 3 for assessing the progression of malignant disease could constitute a new direction for research. Full article

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are graded per the World Health Organization (WHO) using mitotic count and the Ki-67 index. There is an ongoing debate regarding the concordance between these parameters and their ability to predict metastatic disease. Objective: The objective is to assess concordance between the mitotic count and the Ki-67 index in grading GEP-NETs and to determine which parameter more accurately relates to metastatic disease and local tumor behavior. Methods: We conducted a single-center retrospective cohort study of adults with GEP-NETs managed between January 2006 and February 2024. Tumors were staged according to the TNM system. Grading followed WHO criteria using mitotic count and the Ki-67 index; when discordant, the higher grade was assigned. Results: Concordance between mitotic count- and Ki-67-based grading was 76.5% (78/102) with Cohen’s κ = 0.36, indicating fair-to-moderate agreement. More tumors were classified as G1 by mitotic count (86.3%) than by the Ki-67 index (68.6%). Neither mitotic count nor the Ki-67 index (numerical values or grades) showed a significant association with metastatic disease (all p > 0.05). Mitotic count (as a numerical continuous values) correlated with tumor invasion (T1 vs. T3, p = 0.035; T1 vs. T4, p = 0.036), whereas the Ki-67 index did not (p = 0.11). Tumor size was the strongest predictor of metastases (lymph-node p = 0.028; distant p < 0.001; any p < 0.001). Conclusions: Mitotic count and the Ki-67 index show only 76.5% concordance. Neither marker predicted metastatic disease in this cohort, while tumor size was the most robust predictor. These findings support giving greater weight to tumor size within prognostic algorithms while recognizing the limitations of proliferation-based grading for predicting metastasis. Full article

Type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular risk characterized by low-grade inflammation. The aim of this systematic review and meta-analysis was to assess the effects of resistance exercise training (RET) predominantly on cytokines, along with changes in glucose profile and body composition in T2DM patients. The present systematic review and meta-analysis was conducted utilizing PubMed, Web of Science, Embase, and the Cochrane Library databases from their inception up to July 2024 (PROSPERO; registration number CRD420251149352). We screened only for randomized controlled trials investigating the effects of systematic, supervised RET on C-reactive protein (CRP) and adipokines: adiponectin, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), along with changes in anthropometric indices and glycemic control in adult T2DM patients. Pooled post-exercise weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated for all outcomes of interest between exercise-treated patients and controls. Sixteen studies involving a total of 668 T2DM patients were retrieved from the databases for meta-analysis. We used the GRADE framework for assessing the certainty of evidence. Cochran Q-score (I²) was used to estimate heterogeneity among studies (level of significance p < 0.10) and risk of bias analysis was also performed. The cumulative results showed that post-RET inflammatory markers were lower in exercise-treated patients compared to controls regarding CRP (mg/L) (WMD: −0.63; 95%CIs: −1.05, −0.20; p < 0.001); adiponectin (μg/mL) (WMD: −0.94; 95%CIs: −1.49, −0.38; p < 0.001). The results from adiponectin are quite conflicting since they derived from only three studies, where one of them had the greater impact. In parallel, we noticed significant amelioration of fasting glucose and HbA1c (p < 0.001), while body weight remained unaltered. Our meta-analysis demonstrated non-significantly lower levels of IL-6 and TNF-α in RET vs. control group. RET can merely reduce the inflammatory burden in T2DM patients by ameliorating the circulating levels of CRP and adiponectin, while in the rest of the biomarkers, non-significant results were obtained. Hence, the overall clinical impact of those anti-inflammatory effects of RET needs to be determined. Full article

Background: Glioblastomas (GBMs) are the most aggressive and common neoplasms that affect glial cells, presenting rapid growth, invasion, and resistance to treatments. Studies have demonstrated the potentially inhibitory effect of flavonoids on glioblastoma cells’ stemness and viability. However, further research is needed to explore sensitivity and the mechanism of action in chemoresistant cells. Methods: In this study, we characterized the impact of apigenin treatment on the viability and differentiation of human GBM cells in vitro and its effects on tumorigenesis and regulation of the inflammatory response in vivo. Results: The flavonoid apigenin reduced the viability of U-251 cells, patient-derived cells TG-1 and OB-1 stem cells in a dose-dependent manner, associated with the induction of acidic vesicle organelles formation and apoptosis. Treatment with apigenin also inhibited migration and induced neural differentiation in the remaining viable cells, characterized by a decrease in the expression of the precursor marker nestin and an increase in the expression of astrocyte and neuron markers, GFAP and β-III tubulin, respectively. The xenotransplantation of apigenin-pretreated U251 cells into rat brains did not lead to tumor formation, unlike untreated cells. The surrounding area of transplanted untreated U251 cells exhibited reactive microglia and astrocytes, along with increased VEGF expression, which was absent in implant sites of apigenin-pretreated GBM cells. Moreover, in this implant area, we observed a significant decrease in the expression of mRNA for inflammatory factors IL-1β, TNF, and NOS2, and the downregulation of IL-10 and IL-4. Conclusions: These results demonstrate that apigenin inhibits the growth of tumoral cells, affecting the viability of tumor stem cells and impairing tumorigenicity, while altering the regulatory profile of immunomodulatory proteins. Therefore, this flavonoid can be considered for further studies to determine its use as an adjuvant to the treatment of human GBMs. Full article