Uses of Plastic have increased worldwide and phthalate esters - released continuously from plastic matrices due to their non-covalent bonding - are among the most abundantly detected chemical additives in human biomonitoring globally. Seven phthalates are currently designated as High-Priority Substances under active federal risk evaluation by the US EPA under Toxic Substances Control Act (TSCA). Of these, five - di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), diisobutyl phthalate (DIBP), benzyl butyl phthalate (BBP), and dicyclohexyl phthalate (DCP) - were selected based on dominance in environmental detection and biomonitoring data. Despite growing evidence linking phthalates to various diseases, no study has evaluated all five together against a complete signaling pathway spanning membrane, cytoplasmic, and nuclear protein targets. Therefore, dual-engine molecular docking was performed using AutoDock 4 and AutoDock Vina against four resolved TGF-β/SMAD signaling Pathway targets - TGFβRI (3TZM), TGFβRII (5E92), SMAD2 (1DEV), and SMAD3/SMAD4 (1U7F) - the only pathway among 18 studied which have all three cellular compartments. All five showed binding above −6.0 kcal mol⁻¹ at TGFβRI, TGFβRII, and SMAD3/SMAD4 in both engines. Affinity hierarchy was consistent - DCP > BBP > DIBP > DBP > DEHP - across all four targets. At SMAD2, only DCP showed stable binding and remaining four produced no stable/convergent docking pose under the specified conditions. DCP is the least detected yet showed strongest binding - showing environmental prevalence does not predict receptor-level potency. These findings support TSCA cumulative risk assessment and warrant in vitro phosphorylation and SMAD-reporter gene validation, subject to further studies.
PFKFB3 is a druggable regulator of fructose-2,6-bisphosphate production, glycolytic flux, angiogenic metabolism, and tumour-cell survival signalling. This study redesigned the AZ67 allosteric scaffold to prioritise computational leads for anticancer metabolic drug discovery. ChemoDOTS enumeration produced 575,760 virtual products and 509,921 standardised unique structures. A reconstructed two-branch workflow applied sequential molecular-weight, lipophilicity, and relaxed drug-like criteria in one branch and PAINS filtering in parallel; intersection with Brenk-alert exclusion retained 10,996 candidates. Five-objective Pareto ranking and diversity filtering selected 50 compounds. A separate six-descriptor AZ67-referenced triage rule identified 27 comparator-qualified candidates but was not interpreted as proof of improved overall drug-likeness. Three nonredundant representatives—MOL_0052111, MOL_0051973, and MOL_0000552—were selected to test distinct substitution hypotheses, followed by docking in the PFKFB3 allosteric pocket (PDB 5AJV), 50-ns molecular dynamics, and MM/GBSA estimation. GNINA outputs were reported according to their distinct conventions: the empirical docking score was interpreted as more favourable when more negative, whereas CNNaffinity was reported on a positive pK scale, with higher values indicating stronger predicted affinity. The selected derivatives had higher molecular weight and topological polar surface area and lower QED than AZ67, although several had lower logP and higher Fsp3. MOL_0000552 gave an empirical docking score of -7.55 kcal/mol and CNNaffinity of 8.18 pK, compared with -4.33 kcal/mol and 4.21 pK for AZ67. It showed the least variable ligand trajectory among the derivatives and an MM/GBSA profile near -65 kcal/mol versus approximately -40 kcal/mol for AZ67. MOL_0051973 was a secondary lead, whereas MOL_0052111 underwent a marked ligand-RMSD shift after approximately 25 ns. MOL_0000552 therefore represents a prioritised computational hypothesis, not a validated PFKFB3 inhibitor. Biochemical activity, isoform selectivity, cellular effects, ADMET properties, and reproducibility in longer replicate simulations require confirmation.
Introduction: This study investigates the psychosocial determinants of physical activity (PA) in colorectal cancer (CRC) patients, specifically examining the influence of perceived autonomy support from healthcare providers on exercise behavior. Methods: A cross-sectional analytical study was conducted among 72 patients with CRC using two validated scales. Perceived autonomy support was assessed via the Health Care Climate Questionnaire (HCCQ). Motivation to exercise during oncology treatment was measured using the Treatment Self-Regulation Questionnaire (TSRQ). Relationships were analyzed using the computed mean item scores of both instruments. Results: The study results showed a slight male predominance (sex ratio: 1.25) with a mean age of 56±11.94 years. Diagnosis was predominantly late (84.7%), with a high prevalence of stages III and IV (84.7%). Furthermore, the study revealed a non-self-determined profile (index: -2.2), characterized by a healthcare environment perceived as controlling (HCCQ: 2.71). Patients engaged in physical exercise primarily out of guilt or external pressure (controlled regulation score: 5.11) rather than personal conviction (autonomous regulation score: 2.86). Educational level significantly influenced the perception of autonomy support (p = 0.03), to the detriment of the most and least educated patients. Conversely, participants' age and clinical stage (TNM) had no statistically significant impact on the various psychological dimensions assessed (p > 0.05). Conclusion: In light of patient engagement being driven by external constraint, care in colorectal oncology must shift from directive prescription to autonomy support. To achieve this, integrating therapeutic patient education is essential to facilitate the internalization of the health benefits of exercise. Finally, establishing progressive goals proves indispensable for restoring self-efficacy and consolidating the patient’s perceived competence prior to any focus on functional performance.
Introduction: Oral cancer is a malignant neoplasm due to the carcinogenesis process. In this, tumor cells show a deregulation and reprogramming of cellular energy metabolism because production and proliferation of biomass is necessary. Adenosine 5-triphosphate (ATP) represents the currency of energy exchange, an extracellular key signaling molecule to mediate multiple cellular responses. Most metabolic energy originates from oxidation-reduction (redox) reactions in mitochondria, and this organelle could be affected by some of the known risk factors of developing oral cancer such as the intake of alcohol and tobacco. Therefore, ATP is proposed as a prognostic malignant transformation marker and predictive in the progress of cancer. Methodology: Fifteen tissues from oral normal gingiva (controls) and fifteen from oral squamous cell carcinomas (OSCC) were collected. Risk habits were taken and recorded as presence or absence. OSCC clinical stages were taken from medical history, and these were evaluated according to AJCC. ATP was quantified with a luminescence-based (luciferin–luciferase) detection assay. Categorical variables were presented as frequencies and percentages, numerical variables as medians. The Mann-Whitney U non-parametric test was used for statistical analysis. Results: Control group had the highest frequency of not consuming tobacco (n=11, 73.3%). OSCC groups showed a higher frequency of tumor with no invasion of close anatomic sites (<4cm) (n=9, 60%), no clear predilection between presence (n=8, 53.3%) and absence (n=7, 46.7%) of lymph node invasion and despite only one patient reported distant metastases, the more prevalent recorded clinical staging was the advanced stage (n=9, 60%). Smoking cigarettes showed significant influence (p <0.01) to generate higher levels of ATP (median 1.4 µM/µL) compared to non-smokers (median= 0.5 µM/µL), contrary to the group of OSCC cases. ATP concentration was significantly (p<0.001) higher in the case group (median= 1.6 µM/µL) than the control group (median= 0.9 µM/µL). The results involving the aggressiveness of the disease did not show statistical difference. Conclusions: According to this study, in non-malignant oral tissue ATP levels could be influenced by tobacco smoke but apparently this is not applied to OSCC and independently of risk habits ATP levels could be more concentrated in oral malignant tissues increasing the levels of ATP.
Background: Breast cancer accounts for the highest incidence of cancer among Iraqi women. Generic Palbociclib has recently become available, yet there remains a lack of real-world clinical equivalence data. Methods: A prospective observational study carried out between September 2024 & April 2025 at the oncology teaching hospital in the medical city complex with (175) participants included those on generic palbciclib with fluvestrant or Aromatase inhibitor(AI). All participants were completed the study without any dropouts. Results: Neutropenia was common in both AI (88.3%) and Fluvestrant (87.2%) groups. Increase in Anemia was more marked in the Fulvestrant group (93.6%) than in AI (63.3%) with p-value <0.001), and the same for hair loss p=0.005; 46.8% and urticaria (p =0.019 , 19.1%). The mean age in each of the groups was similar (50.8 years vs 51.6 years), indicating that age did not have a significant effect on association found. As all patients had ECOG performance status of 0 to 1, performance status was not considered in the regression analysis because of lack of variability. Conclusion: Generic Palbociclib safety profile is consistent with initial studies and historical data and it’s tolerability is confirmed under-resourced settings.
Background: Early-onset gastric cancer (EOGC) is gastric cancer diagnosed in patients aged below 40 years; EOGC is increasing in frequency, although the immune profile of EOGC is not well studied. Although a major part of gastric carcinogenesis is attributed to chronic inflammation that is frequently due to Helicobacter pylori, the cytokine profiles in the young gastric cancer patients have not been clearly defined. Purpose: The paper will focus on the assessment of the serum pro-inflammatory cytokine profile in EOGC patients and discuss how this parameter is associated with clinicopathological characteristics (tumor stage, grade, and metastasis). Methods: The retrospective observational study design was applied to 50 EOGC patients and 50 healthy age-matched controls. Blood samples were collected, and cytokine levels (IL-1β, IL-6, IL-8, TNF-alpha, IFN- gamma, and IL-18) were determined by ELISA and multiplex bead-based assays. The levels of cytokines were compared in the two groups, and the correlations of the levels with clinical and pathological features were examined. The diagnostic potential of cytokines was investigated using ROC analysis. Findings: The patients of EOGC had a great amount of serum cytokines compared to the healthy controls. There was also a significant increase in IL-6 and IL-1β, which was linked to advanced stages of tumor and metastasis. The ROC analysis revealed that the diagnostic performance of IL-6 and IL-1β was high, with the AUC of 0.85 and 0.82, respectively. Conclusion: Patients with EOGC exhibit a distinctive pro-inflammatory cytokine profile, which suggests that inflammation plays a part in the disease's development. High cytokines like IL-6 and IL-1β can be used as potential biomarkers of early diagnosis and prognosis. These findings should be confirmed with further studies to investigate the therapeutic approach to address the inflammatory pathways in the management of EOGC.
Background: Breast cancer represents one of the most prevalent malignancies, with progression influenced by both tumour biology and the immune microenvironment. However, current prognostic methods have limited accuracy in predicting tumour aggressiveness and long-term outcomes. Tumour-infiltrating lymphocytes, principally CD3⁺ and CD8⁺ T cells, may play an important role in antitumour immunity. Objective: The primary goal of the study is to assess the immunostaining of CD3 and CD8 proteins in malignant and non- malignant breast tissue and to find their association with breast cancer histopathological data using immunohistochemistry. Methodology: This research was conducted between December 2025 and March 2026 at Al-Nasiriyah Teaching Hospital in Thi-Qar, Iraq. Immunohistochemical analysis was performed to evaluate CD3⁺ and CD8⁺ T-cell expression in both malignant (n=100) and non-malignant (n= 40) tissues of the breast. Statistical analyses were applied using unpaired t-tests, Chi-square and one-way ANOVA to assess differences in immunostaining levels between the studied groups. Result: The findings demonstrated that CD3⁺ and CD8⁺ immunostaining levels were significantly elevated in both stromal and intra-tumoural regions of malignant breast tissues compared to benign tissues. The immunostaining of these potential biomarkers was associated with higher tumour grade, larger tumour size, lymph node metastasis, and the molecular subtypes of breast cancer. Conclusion: Increased CD3 and CD8 expression in breast cancer is strongly linked to more advanced histopathological parameters. The findings indicate that these immune biomarkers may reflect the tumour immune microenvironment and contribute to a more comprehensive understanding of tumour progression and host immune response in breast cancer.
The protein JunD plays an important role in cell proliferation, differentiation and apoptosis. In the context of leukemia, particularly acute myeloid leukemia, JunD overexpression has been implicated in disease progression and cell proliferation. However, JunD can also act as a tumor suppressor in certain cancer cases, thus making its role controversial. Here, we investigated the molecular mechanisms by which dichloroacetate (DCA) modulates JunD expression and its impact on chemosensitivity in acute myeloid leukemia (AML) cells, specifically focusing on the involvement of p53. The results showed a significant reduction in JUND mRNA levels in OCI-AML3 (wt-P53) cells treated with 1 and 5 mM DCA (48±6.50 and 53±10.17%, respectively; p< 0.05) compared to untreated cells. On the other hand, in HL60 a P53-Null cell, a significant increase in JunD expression (132.7±6.02%; p< 0.05) was observed when compared to untreated cells. Similar results were observed in OCI-AML3 cells transfected with Si-P53 plasmid to reduce the expression of p53. Additionally, JUND knockdown significantly decreased cell viability (compared to scramble Si-RNA) and further amplified the DCA effect (10.2±1.48%; p< 0.05). Similar results were noticed when cells were subjected to doxorubicin at different concentrations. In particular, the combination of DCA and doxorubicin resulted in enhanced anti-leukemic effects, indicating that JunD is essential for modulating the cellular response to doxorubicin. Overall, we demonstrate for the first time that DCA decreased JunD expression and sensitized leukemic cells to chemotherapy, and these effects may depend on p53 status.
Objective: This research was conducted to examine the part played by epigenetic regulation in up-regulating the expression of ABCB1 (P-glycoprotein) and the role it contributes to the development of taxane resistance in triple-negative breast cancer (TNBC). Methods: Taxane-sensitive and taxane-resistant TNBC cell lines (e.g., MDA-MB-231) were subjected to the evaluation of the ABCB1 expression with the help of the quantitative PCR (qPCR) and the Western blotting procedures. Bisulfite sequencing, chromatin immunoprecipitation (ChIP), and miRNA profiling were used to study epigenetic alterations such as DNA methylation, changes in histone activity (acetylation), and miRNAs, respectively. To test the reversal of resistance, epigenetic inhibitors were utilized and included 5-aza-2'-deoxycytidine and trichostatin A. Patient-derived TNBC samples were used to make clinical correlations that established the connection between the status of ABCB1 methylation and the response to chemotherapy. Findings: The expression of ABCB1 in taxane-resistant cells was found to be much higher in comparison to that of sensitive cells, as determined by both mRNA and protein. The DNA analysis of the methylation of the promoter of the ABCB1 showed that it is hypomethylated in the resistant cells, and the histone acetylation of ABCB1 was also significantly elevated in the resistant cells. miR-451 and miR-335, which regulate ABCB1, were suppressed in the resistant cells. ABCB1 overexpression was reversed by treatment with epigenetic inhibitors, and sensitivity to taxanes was restored. It was found that low levels of methylation of the promoter of ABCB1 were linked to ineffective taxane chemotherapy response in patients with TNBC. Conclusion: Taxane resistance in TNBC occurs with the help of epigenetic regulation of ABCB1. The significant contributors to the overexpression of ABCB1 are DNA hypomethylation, histone acetylation, and miRNA dysregulation. Epigenetic therapies, as an adjunct to the taxane chemotherapy, are one such promising approach that could be used to overcome drug resistance in TNBC, and they should be further explored in clinical trials.
The most prevalent and aggressive type of kidney cancer, which is known to be difficult to treat with standard therapies and has a poor prognosis, is clear cell renal cell carcinoma (ccRCC). It has been suggested that mitochondrial metabolic reprogramming is now a fundamental component of the development of ccRCC that affects energy generation, cell survival, and tumor aggressiveness. The aim of the study is to examine the importance of mitochondrial dysfunction in cRCC through imaging the metabolic changes that occur in the tumor microenvironment. A multi-omics method is used, which combines transcriptomic, metabolomic, and proteomic studies to reveal the metabolic changes that occur in the cells of ccRCC. Found that there were marked changes in some of the important metabolic pathways, such as increased glycolysis and fatty acid oxidation, as well as a significant decrease in the efficiency of oxidative phosphorylation. These were associated with metabolic alterations that correlated with a higher tumor cell survival and expansion in hypoxic conditions, which is typical of ccRCC. Moreover, several important regulators of metabolism, including HIF-1α, AMPK, and PGC-1α, were overexpressed in ccRCC cells and linked to the metabolic changes. Although HIF-1α, AMPK, and PGC-1α emerge as possible therapeutic targets, this paper does not involve any inhibition studies that would demonstrate the therapeutic value of these targets. The evidence presented here is purely correlational, involving only cell line and xenograft models. The given study contributes to the understanding of the metabolic weakness of the ccRCC and refers to the possibility of developing new treatment modalities that could influence the metabolism of mitochondria. Future studies ought to ultimately be on clinical validation of these findings and investigations on the development of mitochondrial-targeted therapies as monotherapies or as adjuncts to existing therapies in order to enhance patient outcomes in ccRCC.
Esophageal squamous cell carcinoma (ESCC) is a very aggressive disease that does not respond to the traditional methods of treatment, including chemotherapy and immunotherapy, and therefore has a low prognosis. Tumor immune microenvironment (TIME) is an important factor that contributes to resistance because it affects the function of immune cells and their interactions with tumor cells. The cellular composition and functional state of the immune microenvironment of the treatment-resistant ESCC were examined in the work by means of single-cell RNA sequencing (scRNA-seq). The populations of immune cells were observed to differ in the event of treatment-resistant and treatment-responsive ESCC. There were more exhausted CD8 + T cells, regulatory T cells (Tregs), and immunosuppressive macrophages in the treatment-resistant group. These cells also had high levels of immune checkpoint markers like PD-1, PD-L1, and CTLA-4, which are identified to play a role in inhibiting effective immune responses. In addition, there was also a metabolic reprogramming of these immune populations with an increased glycolytic activity, which leads to a dysfunction of immune cells and allows tumors to survive. Using gene set enrichment analysis (GSEA), there were a few pathways that were upregulated in the resistant cohort, such as immune checkpoint signaling, inflammatory responses, and metabolism pathways. These observations support the assumption that immune escape and metabolic restructuring are two influential factors in ESCC resistance. The findings indicate that both immune checkpoints and the metabolic reprogramming of immune cells may be combined therapies to provide a promising approach in overcoming treatment resistance in ESCC. The findings need to be validated in future studies with larger patient groups, multi-omics studies, and clinical trials to come up with better treatment options among ESCC patients.
One of the most deadly and malignant cancers is pancreatic cancer, and there is a very limited available therapy, and the patients die from the cancer. For treating pancreatic cancer, one of the most extensively used chemotherapeutic agents is gemcitabine, and its clinical efficiency is hindered by its rapid metabolism, minimal tumor accumulation, and systemic toxicity. The aim of this study is to construct a dual-responsive nanoparticle system for targeting and controlled release of gemcitabine in the pancreatic tumor microenvironment for enhanced therapeutic outcome of the drug. These prepared nanoparticles were sensitive to pH as well as temperature and consequently showed tumor-specific release of gemcitabine with reduced off-target side effects. In vitro and in vivo studies with pancreatic cancer models were performed to assess the therapeutic activity of the formulation. The cellular uptake experiments showed efficient uptake of the nanoparticles by PANC-1 pancreatic cancer cells, leading to improved drug delivery into cells. Evaluation of the cytotoxicity showed that the anticancer activity of the therapy using the nanoparticles was significantly better with an IC50 value of 4.8µM versus 12.5µM for free gemcitabine. In a murine pancreatic tumor xenograft, gemcitabine-loaded nanoparticles were able to inhibit tumor growth by 45%, while free gemcitabine was able to inhibit tumor growth by 20%. Moreover, the dual-responsive system showed controlled and sustained drug release in tumor-relevant conditions, which improved the therapeutic targeting. The plasma exposure of the drug in the nanoparticle formulation was enhanced by about 4-fold (AUC0-24h 86.4 vs. 21.7 µg·h/mL) and the tumor accumulation of the drug was enhanced by about 5-fold (8.4 vs. 1.6 %ID/g) compared to free gemcitabine, and the plasma level of hepatic enzymes was within normal range in the nanoparticle animals, while plasma exposure of free gemcitabine showed significant elevation in levels of ALT (p = 0.01), directly supporting the reduced systemic toxicity of the formulation. The results show that delivery of gemcitabine using nanoparticles with dual responsiveness can significantly improve the antitumor activity and drug bioavailability and decrease systemic toxicity based on preclinical pharmacokinetic and biochemical evidence in a single xenograft model. The proposed strategy is a promising proof-of-concept strategy for the enhancement of pancreatic cancer treatment and an example of stimulus-responsive nanomedicine platforms in precision oncology. Additional preclinical studies are needed to prove long-term safety and to translate it into clinical use.
Glioblastoma treatment is a real challenge despite better understanding of molecular characterization of gliomas. More effective treatment protocols are urgently required. The current study compared the efficacy of combined Temozolomide/CCNU versus temozolomide (standard or extended) for patients with methylated O6-methylguanine-DNA-methyltransferase (MGMT) Glioblastoma. Method: The current trial is a prospective, randomized, open-label study including ninety participants initially diagnosed with glioblastoma isocitrate dehydrogenase (IDH) wildtype, methylated MGMT promoter. The Participants were randomly allocated (1:1:1) to concomitant and adjuvant temozolomide/CCNU combined therapy, standard temozolomide or temozolomide extended therapy. The main end point was overall survival. Other endpoints were progression-free survival and toxicity. Results: In the current study, the median overall survival was significantly higher in temozolomide/CCNU group (43 months) and extended temozolomide group (40 months) compared to standard temozolomide group (30 months). The median progression free survival was longer with temozolomide/CCNU and extended temozolomide compared to standard temozolomide without significant correlation (95% CI 0.815-1.496; p=0.055). Conclusion: Multivariate analysis revealed that Eastern Cooperative Oncology Group (ECOG) scale ≤1 continued as a significant prognostic variant with overall survival in different treatment groups Conclusion: The effectiveness and safety of combined CCNU/ temozolomide and extended adjuvant temozolomide should be considered for treatment of recently diagnosed IDH-wildtype glioblastoma with MGMT methylated.
Introduction: BRCA mutation status plays a pivotal role in determining sensitivity to PARP inhibitors. however, its influence on the clinical benefit derived from Bevacizumab remains less clearly established. This study aims to assess survival outcomes of Bevacizumab in advanced high-grade serous ovarian cancer (HGSOC) based on BRCA mutation status. Methods: The study included 101 patients with advanced HGSOC who were diagnosed and treated at Tanta University Hospital. All patients were tested for BRCA1/2 mutations. Patients received six cycles of weekly carboplatin and paclitaxel, with or without Bevacizumab, followed by maintenance Bevacizumab. Patients were categorized into two groups based on whether they received Bevacizumab or not, and were further stratified according to BRCA mutation status. Results: Bevacizumab significantly improved progression-free survival (PFS) among patients with BRCA wild-type tumors (median PFS was 24.0 months versus 18.0 months, HR (95% CI: 0.1764 (0.07581 to 0.4103), P = 0.012). BRCA-mutated patients did not show a significant PFS advantage (median PFS 23 vs. 20 months, P = 0.111). OS did not differ significantly with the use of Bevacizumab, either in the BRCA wild-type or mutated group. Univariate analysis identified FIGO stage and residual tumor (RT) as significant predictors of PFS. In the multivariate model, only the residual tumor remained significant. For OS, the FIGO stage was the sole significant factor. Conclusion: Bevacizumab added a significant PFS advantage in BRCA wild-type patients, while patients with BRCA mutations did not achieve the same benefit, suggesting that Bevacizumab may be prioritized for BRCA wild-type patients.
Breast cancer is among the most common cancer in women worldwide. It is accompanied by significant psychosocial, cultural, and spiritual challenges that have a substantial impact on treatment adherence, care-seeking behavior, and perceptions of the disease. These psychosocial aspects of cancer are still largely unexplored in Tajikistan, where stigma, cultural norms, and the dearth of organized psycho-oncology services all contribute to increased distress, delayed diagnosis, and low patient engagement. In order to direct the methodical integration of psychosocial care into breast cancer control, this perspective paper suggests a hybrid psycho-oncology framework for Tajikistan based on transferable and contextually relevant models from Africa and India. Instead of serving as a supplemental mental health intervention, it seeks to understand how culturally sensitive psycho-oncology can serve as a fundamental part of oncology services in a setting with limited resources and high stigma. The study explores culturally mediated barriers that influence screening behaviour, diagnostic engagement, and treatment adherence among Tajik women, including fear of social exposure, body image disruption, gendered distress, and privacy-related anxieties. It does this by combining clinical insights and established psycho-oncology practices from similar low- and middle-income contexts. The analysis demonstrates how structured interventions can enhance early detection, continuity of care, and quality of life. These interventions include regular distress screening, counselling, community engagement, family-inclusive care, and palliative psychosocial support. Instead of offering empirical results, this viewpoint promotes a translational framework for cooperatively integrating psycho-oncology into Tajikistan's cancer care system. As a scalable approach for workforce development, capacity building, and long-term integration of psycho-oncology into cancer care systems throughout Central Asia, it suggests a tripartite collaborative model involving Tajikistan, India, and Uganda.
Bone cancers have diverse radiologic and histopathologic characteristics, and visual ambiguity frequently constrains single-modality AI. To create a tri-modal system that learns from (i) radiographs in the Bone Cancer Detection (Kaggle) dataset, (ii) whole-slide images (WSIs) with weak labels through multiple-instance learning (MIL), and (iii) RNA-seq±mutation profiles (TARGET-OS) represented by a compact variational/Multi Layer Perceptron (MLP) bottleneck. To align modality latents with Maximum Mean Discrepancy (MMD) and Information Noise-Contrastive Estimation (InfoNCE) contrast, and then to employ reliability-aware late-fusion with optional cross-modal co-attention to combine them. Temperature scaling adjusts the chances. The fused model gets Accuracy of 0.926±0.016, Macro-averaged F1 score of 0.914±0.018, Area Under the Receiver Operating Characteristic Curve (AUROC)of 0.965±0.010, Area Under the Precision–Recall Curve (AUPRC)of 0.958±0.011, Brier score of 0.067±0.008, and Expected Calibration Error (ECE)of 0.018±0.006 on tests that were held out. Single streams do worse (Radiograph AUROC 0.940; WSI-MIL 0.918; Omics 0.902), while two-stream combinations close much of the gap. Ablations show that alignment and co-attention are quite important (for example, taking out MMD lowers AUROC by 0.012 and raises ECE by 0.006). Robustness experiments demonstrate elegant decline in the presence of X-ray blur/jitter, stain jitter, and omics batch shifts; the external-site AUROC remains robust at 0.958 (fused). An adjusted operating point θ* gives Coverage 94.1%, Sensitivity 0.936, Specificity 0.903, Positive Predictive Value (PPV) 0.907, Negative Predictive Value (NPV) 0.933, and the best utility when costs are high for false negatives. This study shows that combining morphologic and molecular signals with an awareness of uncertainty leads to accurate, well-calibrated, and more generalizable predictions of bone cancer. This is true even when only radiographs are available.
Objective: This study was performed to evaluate the cytotoxic effects and synergistic interactions of Albendazole combined with Etoricoxib on HeLa cervical carcinoma cells, emphasizing mechanisms involving disruption of glycolytic metabolism and cellular pH regulation. Materials and Methods: The study investigated the cytotoxic effects of Albendazole, Etoricoxib, their combination, and 5-Fluorouracil (5-FU) on HeLa cells and normal human foreskin fibroblasts (HFF) via MTT assays. It also calculated the Combination Index (CI) and Dose Reduction Index (DRI) using CompuSyn software to evaluate drug synergy. Furthermore, lactate production and carbonic anhydrase activity were measured to analyze glycolytic flux and pH regulation, and were complemented by molecular docking of the drugs with β-tubulin and carbonic anhydrase IX. Results: The combination of Albendazole and Etoricoxib exhibited significant synergistic cytotoxic effects against HeLa cells, compared to either agent alone or 5-Fluorouracil (5-FU). The combination also showed high selectivity, indicating a sparing impact on HFF cells, unlike 5-FU. Furthermore, the combined treatment markedly inhibited lactate production by 85.1% and carbonic anhydrase activity by 86.3%. Molecular docking studies corroborated these findings by revealing stable binding interactions of Albendazole with β-tubulin and Etoricoxib with CA-IX, with docking scores of -6.7 and -7.1 kcal/mol, respectively, supporting a dual-targeting mechanism. Conclusion: The combined use of Albendazole and Etoricoxib produces a synergistic effect on cervical cancer cells by disrupting glycolytic metabolism and cellular pH regulation. This targeted approach offers a promising way to overcome chemoresistance and lessen toxicity, thereby improving therapeutic effectiveness in cervical cancer treatment.
Background: Thyroid nodules with cytological features of atypia of undetermined significance (AUS), particularly those with nuclear atypia, represent a diagnostic challenge due to their variable malignancy risk. The 2023 revision of the Bethesda System has refined AUS subcategories to improve malignancy risk stratification. The aim of this study was to evaluate the risk of malignancy in Bethesda Category III thyroid nodules with nuclear atypia by correlating cytological findings with post-thyroidectomy histopathological results. Material and Methods: This retrospective observational study included 156 patients who underwent thyroid fine-needle aspiration cytology between 2020 and 2024 and were diagnosed with AUS featuring nuclear atypia. All patients subsequently underwent thyroidectomy. Malignancy rates were determined based on final histopathological diagnoses. Statistical analysis was performed using SPSS version 29.0, applying Chi-square and Fisher’s exact tests, with a significance threshold set at p < 0.05. Results: The overall malignancy rate was 34.6%, increasing to 39.7% when NIFTP cases were included Fifty papillary carcinomas were identified, 28 of which were <1 cm. In 23 patients who received repeated AUS diagnoses, the malignancy rate reached 73.9% (p = 0.011). No statistically significant differences were found between benign and malignant groups in terms of age (p = 0.655), gender (p > 0.05), or lymphocytic thyroiditis (p = 0.3). The reported malignancy rates were exclusively to the cohort of Bethesda Category III nodules with nuclear atypia, which constituted the entire study population. Conclusion: Thyroid nodules classified as AUS with nuclear atypia are associated with a higher-than-expected risk of malignancy, especially in cases with repeated AUS diagnoses. These findings underscore the importance of subclassifying AUS cases to improve risk stratification and guide clinical decision-making.
Glioblastoma multiforme (GBM) is the most aggressive and lethal primary brain tumor, with an average survival of no more than 15 months despite advances in surgery, chemotherapy, and radiotherapy. Linking imaging phenotypes with genomic frameworks can improve personalized prognosis and treatment planning. This study develops a deep learning-based radiogenomic framework that integrates high-dimensional imaging features extracted from multiparametric MRI using a convolutional neural network (CNN) with key molecular biomarkers, including EGFR amplification, IDH mutation, and MGMT promoter methylation. A multiomics fusion module combined imaging-derived features with genomic alterations to enable stratified survival prediction. The publicly available datasets were used to train and validate the framework, i.e., TCIA and TCGA-GBM. The CNN-based radiogenomic model was more successful than the traditional radiomic and dictionary learning -based approaches, with high prognostic accuracy. Survival stratification into high- and low-risk groups showed significant differences, as confirmed by Kaplan–Meier analysis, C-index, and AUC metrics. The radiogenomic markers based on the model obtained biologically meaningful information on tumor heterogeneity and a better predictive outcome than the traditional methods. Radiogenomic signatures based on deep learning make it possible to prognosticate GBM accurately, non-invasively, and biologically in a manner that is precise, relevant, and now more useful in the field of neuro-oncology. The next step in research involves future multi-institutional validation, explainable AI integration, and adding more omics data to make prognostics more accurate and clinically applicable.
Brain tumors and multiple sclerosis (MS) are complex medical conditions characterized by overlapping clinical and imaging features, posing significant challenges in accurate diagnosis. Building upon our previous work, which utilized axial MRI images for classification into three categories—normal, brain tumor, and MS—this study extends the methodology to incorporate sagittal and coronal orientations. Individual convolutional neural network (CNN) models are trained for each orientation, and their outputs are integrated using an ensemble framework with a voting mechanism. This approach leverages the complementary spatial information provided by multi-orientation analysis to enhance diagnostic precision. Experimental evaluations demonstrate that the ensemble model achieves superior classification accuracy and robustness in contrast to the single-orientation approach. This piece emphasizes the vital role that multi-orientation MRI analysis plays in mitigating diagnostic ambiguities and advancing the reliability of AI-driven medical imaging frameworks.
