Search Results (70,852)

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy, often diagnosed at advanced stages with poor survival outcomes. Homologous recombination (HR), a major DNA double-strand break (DSB) repair pathway, safeguards genomic stability via error-free repair. While HR deficiency has been well established as a driver of genomic instability and tumorigenesis in several cancer types, the role of HR in HNSCC remains relatively understudied. Methods: Here, we analyzed the expression patterns of key HR proteins in HNSCC and investigated their association with clinical parameters, DNA methylation, immune cell infiltration, and patient survival outcome. Results: Surprisingly, our results demonstrate that HR factors are consistently upregulated in HNSCC, in both HPV-positive and HPV-negative groups. Survival analysis identified many HR factors, including ATM, BRCA1, BRCA2, PALB2, LIG1, RPA1, and RPA2, as potential prognostic biomarkers for better overall survival. Interestingly, we observed a significant correlation between HR protein overexpression and immune cell infiltration in HNSCC, suggesting a potential immunomodulatory role of HR proteins. To experimentally validate this association in both HPV-positive and -negative cell lines, we showed that MRE11 and RAD51 overexpression in HNSCC cells led to increased phosphorylation of IRF3 and STAT1, indicating activation of the cGAS/STING-mediated innate immune signaling. Conclusion: Together, our findings provide a comprehensive overview of the HR pathway in HNSCC, highlighting the dual role of HR proteins in both genomic maintenance and immune regulation. The consistent upregulation of HR proteins, their association with disease progression, and potential immunogenic effects underscore their promise as diagnostic/prognostic biomarkers and therapeutic targets in HNSCC. Full article

Background: Fluid shear stress (FSS) is a biomechanical force that can produce phenotypic changes in the cells that are directly in contact with the flow of fluid. Accumulating evidence indicates high FSS to possess the potential ability to prevent tumor development and suppress cancer growth. However, the exact mechanism of its antitumorigenic effects is still not clear. Objective: In this study, we aimed to investigate the effect of FSS on breast cancer microenvironment via macrophage modulation. Methods: We exposed THP-1 like-macrophages to different levels of FSS. The supernatant from THP1-like-macrophages after exposure to FSS was used as conditioned medium (FSS-CM). Subsequently, we analyzed human breast cancer cells, MCF-7, and endothelial cells, as well as HUVECs cultured with FSS-CM. Results: Study outcomes have demonstrated that low FSS-CM inhibited apoptosis as well as induced tumor migration in MCF-7 cells. Conversely, high FSS-CM promoted apoptosis, inhibited tumor migration, and induced G1-phase arrest in MCF-7 cells. Furthermore, low FSS-CM was found to promote proliferation of HUVECs. Conclusions: In conclusion, this study highlights the complex interplay between FSS and cancer cell behavior. Our findings provide in vitro evidence that high FSS exerts an anti-cancer effect by promoting THP-1-like macrophage polarization toward an anti-tumor phenotype, leading to increased apoptosis and reduced migration in MCF-7 cells. These results suggest that the modulation of macrophage polarization may underlie the therapeutic potential of high FSS in suppressing breast cancer progression. Full article

CD36, a fatty acid scavenger receptor expressed in tumors, is associated with a poor prognosis in several cancers. Our previous research demonstrated the involvement of CD36 in the proliferation and migration of oral squamous cell carcinoma (OSCC) cells. However, the clinical significance of CD36 expression in OSCC remains unclear. The purpose of this study was to evaluate the association between CD36 expression and the clinicopathological characteristics of OSCC patients. Immunohistochemical expression of CD36 was quantified using the H-score, and its association with clinicopathological characteristics was evaluated in 55 OSCC patients. The mean H-score for membrane-associated CD36 expression was 84.8. CD36 expression was significantly correlated with tumor stage, mode of invasion, differentiation, and recurrence of OSCC cells. Moreover, elevated CD36 expression was significantly correlated with a high rate of relapse. Univariate and multivariate analyses showed that CD36 expression was an independent risk factor for relapse. Moreover, The Cancer Genome Atlas (TCGA) dataset analysis revealed that CD36 expression may coexist with transcriptional activation of β-oxidation-related and epithelial–mesenchymal transition (EMT)-related pathways. These findings suggest that CD36 might serve as a predictive biomarker for OSCC malignancy and recurrence. Full article

Cancer reversion therapy represents a paradigm shift in oncology, focusing on reprogramming malignant cells to a non-malignant state rather than destroying them. This narrative review synthesizes current evidence, emerging technologies, and future directions in this promising field. Cancer reversion is founded on key biological observations: somatic cell reprogramming, spontaneous cancer regression, and microenvironmental influences on malignant behavior. Current approaches include epigenetic reprogramming using HDAC inhibitors and DNA methyltransferase inhibitors; microenvironmental modulation through extracellular matrix manipulation and vascular normalization; differentiation therapy exemplified by all-trans retinoic acid in acute promyelocytic leukemia; and targeting oncogene addiction as demonstrated in BCR-ABL-driven leukemias. Emerging technologies accelerating progress include single-cell analyses that reveal cancer heterogeneity and cellular state transitions; CRISPR-based approaches enabling precise genetic and epigenetic manipulation; patient-derived organoids that model tumor complexity; and artificial intelligence applications that identify novel reversion-inducing agents. Critical evaluation reveals that many reported “reversion” phenomena represent stimulus-dependent plasticity or transient growth arrest rather than stable phenotypic normalization. True cancer reversion requires durable, heritable phenotypic changes that persist after treatment withdrawal, with evidence of epigenetic consolidation and functional restoration. Despite promising advances, significant challenges remain: cancer cell plasticity facilitating therapeutic escape, difficulties in establishing stable reversion states, delivery challenges for solid tumors, and the need for combination approaches to address tumor heterogeneity. Future directions include integrated multi-omics analyses to comprehensively map cellular state transitions, studies of natural regression phenomena to identify reversion mechanisms, advanced nanodelivery systems for targeted therapy, and synthetic biology approaches creating intelligent therapeutic systems. By redirecting rather than destroying cancer cells, reversion therapy offers the potential for reduced toxicity and resistance, potentially transforming cancer from a deadly disease to a manageable condition. Full article

Background: Chemotherapy, targeted therapy and radiotherapy are the cornerstones of cancer treatment. However, therapeutic resistance—not only to these classic modalities but also to novel therapeutics like immune checkpoint inhibitors (ICIs) and antibody-drug conjugates—remains a major hurdle. Resistance significantly limits efficacy and increases recurrence rates. A deep understanding of the molecular mechanisms driving this resistance is critical for developing personalized therapeutic strategies and improving patient outcomes. Recent Advances: Patient-derived cancer organoids have emerged as a powerful preclinical platform that faithfully recapitulates the genetic, phenotypic, and histological characteristics of original tumors. Consequently, PDOs are being widely utilized to evaluate drug responses, investigate resistance mechanisms, and discover novel therapeutic targets for a range of therapies. Limitations: While organoid models have been instrumental in studying resistance, significant limitations persist. First, standard organoid-only models lack key tumor microenvironment components, such as immune cells, limiting immunotherapy research. Second, there is a significant lack of research on acquired resistance, particularly in lung cancer. This gap is largely driven by the clinical infeasibility of rebiopsy in patients with progressive diseases. Third, the absence of standardized protocols for generating and validating resistance models hinders reproducibility and complicates clinical translation. Conclusions: This review summarizes recent advances in using organoid models to study resistance to chemotherapy, radiotherapy, and novel therapeutics (ICIs and ADCs). We emphasize the critical need for standardization in resistance organoid research. We also propose future directions to overcome existing challenges, including the integration of co-culture systems (to include the TME) and advanced technologies (e.g., scRNA-seq, Spatial Transcriptomics). Our specific focus is on advancing lung cancer resistance modeling to enable functional precision medicine. Full article

Introduction: Natural Orifice Transluminal Endoscopic Surgery (NOTES) via the vagina (vNOTES) has recently appeared on the gynecology horizon as a fresh minimally invasive approach. Although vNOTES for benign adnexal conditions is being increasingly employed, very limited experiences exist for its application in ovarian tumors. In this review, the current state of vNOTES applicability for borderline ovarian tumors (BOTs) and estimated early-stage epithelial ovarian cancer (EOC) is assessed. Methods: A narrative literature review was performed to examine operative viability, perioperative safety and functional outcomes, and oncologic details as documented for patients with ovarian tumors undergoing vNOTES. Results: In the current literature, vNOTES has been utilized for adnexectomy, hysterectomy, infracolic omentectomy, peritoneal biopsies, and sampling of selective pelvic lymph nodes in carefully selected patients. The perioperative parameters—bleeding, perioperative pain, and length-of-stay indicators—have been satisfactory with minimal complications. For BOT, vNOTES can meet the requirements for all surgical goals except lymphadenectomy for metastasis evaluation for systemic management. In this context, lymphadenectomy is not necessary for BOT and therefore is no contraindication for vNOTES. However, for invasive EOC, this is a significant drawback as there is no lymphadenectomy for the evaluation and management for this complex subgroup. The oncology follow-up is prematurely limited and is heterogeneous and underpowered. Conclusions: Based on current available data, vNOTES is possible in a selected group of patients with borderline ovarian tumors and in patients with adnexal lesions that are believed to be in early-stage disease based upon imaging studies. For the treatment of invasive epithelial ovarian cancer, vNOTES should not be considered an independent staging procedure at any FIGO stage, but it might find a supplemental place in the setting of a hybrid procedure in a highly selected group of patients in an experienced center. Full article

CDK4/6 inhibitors exert effective anti-tumor effects by blocking the cell cycle and, as a result, have become vital in the systemic treatment of malignant tumors. Previous research has indicated that CDK4/6 inhibitors not only exert effects on the cell cycle but also have regulatory roles in tumor immunity, although the research findings are controversial. This study comprehensively summarizes the molecular mechanisms by which CDK4/6 inhibitors activate or suppress anti-tumor immunity and reveals the dual effects of CDK4/6 inhibitors on influencing interferon signaling, mediating senescence, and altering certain immune cells. In addition, the results of clinical trials of CDK4/6 inhibitors combined with immunotherapy are thought-provoking, with the severe adverse events that occur after treatment being the main factor affecting their therapeutic effect. Therefore, the future direction of this combined treatment strategy deserves further exploration. Full article

Assessing cytotoxicity towards human cells is a critical step in preclinical drug development. In preclinical toxicology, human cell lines allow for the analysis of both general and organ-specific toxicity, thus, helping reduce development time and costs. Predicting cytotoxic IC₅₀ and GI₅₀ values facilitates the early evaluation of new pharmaceutical agents by assessing the possible therapeutic window. Ten non-tumor and 10 tumor cell lines commonly used in toxicology were selected to develop QSAR models using GUSAR software and ChEMBL data. GUSAR employs atom-centric electrotopological QNA and substructural MNA descriptors to encode molecular structure and utilizes the RBF–SCR algorithm to train QSAR models. The best-performing models (R² > 0.5, RMSE < 0.8; mean R² = 0.691, mean RMSE = 0.584) were selected using 5-fold cross-validation. These models were implemented in the freely available web application CLC-Pred 2.0 (Cell Line Cytotoxicity Predictor), initially developed for qualitative prediction of cytotoxicity in human cell lines. Full article

Objective: The Italian Drug Agency (AIFA) Determination n. 589 of 2015 (Note 79) establishes that the use of bisphosphonates or denosumab is necessary for the primary prevention of bone fractures in postmenopausal patients with early breast cancer (EBC) undergoing adjuvant endocrine therapy (ET). Since adherence to the 2015 AIFA recommendation was still very low in 2019, a new bone health management model was identified to improve adherence to this recommendation. Methods: The aim of this project (Predict & Prevent) was to increase the percentage of patients with early breast cancer (EBC) with hormone receptor-positive (HR+) tumors treated. The project identified a new bone health model of management including the following: training of breast multidisciplinary teams and bone health specialists; presentation and implementation of this model in cancer centers; evaluation, at baseline and 12 months after the implementation of the project, of two key performance indicators (KPIs): rate of HR+ EBC patients assessed for bone health within 30 days from the start of adjuvant ET (KPI-1) and rate of HR+ breast cancer patients receiving bisphosphonates or denosumab within 90 days from the start of adjuvant ET (KPI-2). The primary endpoints of this study were the assessment of the rates of the two key performance indicators (KPIs) 12 months after the start of the project (T3) in comparison with the rates recorded at time 0 (T0) in each participating cancer center and the bone fracture rates at 5 years. In this first analysis, we reported the rates of two KPIs 12 months after the start of the new model (T3) and the comparison with the rates recorded at time 0 (T0) in each participating cancer center, to assess whether these percentages had increased after the implementation of the new organizational model. The rates of bone fractures will be evaluated after five years from implementation of this project in every cancer center. Results: From 2020 to 2022, 10 Italian cancer centers were involved in this project. As of September 2023, 9 cancer centers reported rates relative to two KPIs assessed in each hospital. In 6 hospitals (Negrar, Brescia, Bergamo, Aviano, Turin, Rome), the rates relative to KPI-1 and to KPI-2 increased progressively from time T0 (at baseline) to time T3 (after 12 months from the start of the project), due to training of multidisciplinary teams and implementation of a new bone health management model. In the other three cancer centers (Ancona, Genoa, Naples), where the rate of evaluation of bone health (KPI-1) and the indication for bisphosphonates/denosumab (KPI-2) in HR+ EBC patients were already high at time T0, the rates remained high even after 12 months from the start of this project. Conclusions: After 12 months from the implementation of this new organizational model of bone health management, an increase in the rate of postmenopausal HR+ EBC patients on adjuvant ET assessed for bone health and the rate of patients treated with bisphosphonate/denosumab were reported in six out of nine cancer centers. In the other three cancer centers, where the rates were high at baseline, the rates also remained high after 12 months from the new model implementation. This new model should be adopted in all cancer centers to allow adequate management of bone health in all postmenopausal HR+ EBC patients undergoing adjuvant ET, with the ultimate goal of reducing the rate of bone fractures in these patients in subsequent years. Full article

Objectives: Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma characterized by rapid proliferation, early metastasis, and limited therapeutic response. Metabolic reprogramming is increasingly recognized as a key feature of small cell lung cancer progression, yet the contribution of specific metabolic enzymes remains incompletely understood. This study aimed to investigate the role of asparagine synthetase in small cell lung cancer tumorigenicity and disease progression. Methods: Integrative analyses were performed using public transcriptomic datasets, proteomic profiling, and functional assays in vitro and in vivo. Asparagine synthetase expression levels were evaluated in normal lung, non-small cell lung cancer, and small cell lung cancer tissues using public microarray datasets. Loss of function studies were conducted using shRNA mediated knockdown in murine and human small cell lung cancer cell models. Tumor growth and survival were assessed using xenograft mouse models. Results: Asparagine synthetase expression was significantly elevated in small cell lung cancer compared with normal lung and non-small cell lung cancer tissues. Genetic depletion of asparagine synthetase impaired cellular proliferation and colony forming capacity in vitro. In vivo, asparagine synthetase knockdown suppressed tumor growth and was associated with prolonged survival in xenograft mouse models. Conclusions: These findings demonstrate that asparagine synthetase contributes to tumor growth and metabolic adaptability in small cell lung cancer. The results support a functional role for asparagine synthetase in malignant progression and suggest that targeting asparagine metabolism may represent a potential therapeutic approach in aggressive small cell lung cancer. Full article

Background: Epidemiological studies on benign epithelial salivary gland tumors are challenging due to their rarity, pathological heterogeneity, variable tumor locations, and the limited national data collection in Romania. Our study aimed at the evaluation of benign epithelial salivary gland tumors collected over fifteen years in a tertiary center, in order to characterize their demographic and histopathological profiles and to contribute to their diagnostic and therapeutic strategies. Materials and Methods: A retrospective analysis of 404 cases of benign epithelial salivary gland tumors diagnosed in “Sf. Spiridon” County Hospital, Iasi, from 2010 to 2024, has been performed. Results: The analyzed cases showed a slight female predominance (52.97%) and a mean patient age of 54.55 ± 14.207 years. Tumor frequency increased progressively with age, peaking in the sixth and seventh decades of life. The most common histological types were pleomorphic adenoma (62.62%) and Warthin tumor (29.95%), both types showing a predominant parotid gland involvement (88.51%). The recurrences were rare, being registered only in 1.58% of pleomorphic adenomas. A significant association between tumor histological type and both gender (p < 0.001) and age group (p < 0.001) was registered, while no significant correlation between gender and age group (p = 0.288) or between tumor location and gender or age group (p = 0.382; p = 0.383) was found. Conclusions: The frequency of pleomorphic adenoma is increasing, showing an age-related distribution and parotid gland propensity. Key morphological features in each histological type support a better preoperative stratification, a more confident margin assessment, and an individualized extent of excision with function preservation. Full article

Despite advances in deep learning, brain tumor detection from MRI continues to face major challenges, including the limited robustness of single-modality models, the computational burden of transformer-based architectures, opaque fusion strategies, and the lack of efficient binary screening tools. To address these issues, we propose a lightweight multimodal CNN framework that integrates T1, T2, and FLAIR MRI sequences using modality-specific encoders and a channel-wise fusion module (concatenation followed by a 1 × 1 convolution). The pipeline incorporates U-Net-based segmentation for tumor-focused patch extraction, improving localization and reducing irrelevant background. Evaluated on the BraTS 2020 dataset (7500 slices; 70/15/15 patient-level split), the proposed model achieves 93.8% accuracy, 94.1% F1-score, and 19 ms inference time. It outperforms all single-modality ablations by up to 5% and achieves competitive or superior performance to transformer-based baselines while using over 98% fewer parameters. Grad-CAM and LIME visualizations further confirm clinically meaningful tumor-region activation. Overall, this efficient and interpretable multimodal framework advances scalable brain tumor screening and supports integration into real-time clinical workflows. Full article

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and remains a major challenge in contemporary oncology, where early detection is critical for improving treatment outcomes and survival. Despite significant progress in diagnostics and therapy, the epidemiology, risk factors, and molecular mechanisms driving CRC development continue to be intensively investigated. This paper provides an overview of current trends in CRC diagnosis and management, with particular emphasis on advances in molecular medicine and biological sciences. Screening recommendations in Poland are discussed, comparing invasive methods—such as colonoscopy, sigmoidoscopy, and CT colonography—with non-invasive stool-based tests (FOBT, FIT, sDNA-FIT), and evaluating their sensitivity, specificity, and impact on mortality reduction. Key tumor markers with diagnostic, prognostic, and predictive value, including CEA, CA19-9, mSEPT9, ctDNA, TPS, TAG-72, CTCs, and circulating microRNAs, as well as p53 and PTEN proteins, are reviewed in the context of their clinical utility in early detection, disease monitoring, and treatment response assessment. The analysis also highlights the epidemiological situation in Poland and underscores the growing importance of integrating molecular biomarkers with traditional diagnostic methods, which may ultimately support the development of more precise and individualized clinical management strategies in the future. Full article

Breast cancer is a substantial and growing public health issue in India, with epidemiological data demonstrating distinct and often severe disease characteristics in contrast to Western countries. Contrary to the global trend, Indian women frequently develop the disease at an earlier age and tend to present with more advanced stages, emphasizing important variations in disease pathophysiology. This review compiles and critically evaluates the current literature to describe the specific pathophysiology of breast cancer in the Indian population. We investigate the unique cellular and molecular landscapes, evaluate the impact of specific Indian demographic and genetic features, and highlight crucial gaps in knowledge, diagnostic tools, and therapeutic approaches. The assessment reveals a molecular landscape determined by the incidence of specific tumor subtypes; triple-negative breast cancer, for instance, is frequently diagnosed in younger women, and genetic profiling research suggests variations in its susceptibility genes and mutation patterns when compared to global populations. While this paper brings together recent advancements, it highlights the challenges of adopting global diagnostic and treatment guidelines in the Indian healthcare system. These challenges are largely due to variances and specific demographic and socioeconomic discrepancies that create substantial hurdles for timely diagnosis and patient care. We highlight significant gaps, such as the need for more complete multi-omics profiling of Indian patient cohorts, an absence of uniform and readily available screening programs, and shortcomings in healthcare infrastructure and qualified oncology experts. Furthermore, the review highlights the crucial need for therapeutic strategies tailored to the distinct genetic and demographic profiles of Indian breast cancer patients. We present significant strategies for addressing these challenges, with a focus on integrating multi-omics data and clinical characteristics to gain deeper insight into the underlying causes of the disease. Promising avenues include using artificial intelligence and advancements in technology to improve diagnostics, developing indigenous and affordable treatment options, and establishing context-specific research frameworks for the Indian population. This review also underlines the necessity for personalized strategies to improve breast cancer outcomes in India. Full article

Background: Oral squamous cell carcinoma (OSCC) is a highly aggressive neoplasm characterized by grim survival outcomes, despite significant therapeutic advances. Mortality rates (up to 70%) have remained unaltered for decades, predominantly due to profound diagnostic delays. These derive from the asymptomatic nature of the early stages of oral carcinogenesis and the emergence of dysplastic areas in previously benign lesions, acting as the bridge to malignant transformation. Hence, the establishment of reliable salivary biomarkers is crucial for non-invasive OSCC detection, even from the premalignant stage of dysplasia. Based on our previous bioinformatic research identifying stage-specific miRNAs throughout OSCC progression, which yielded miR-34a-5p as the most significant, we aimed to experimentally investigate its role in oral oncogenesis and explore its stage-reflecting biomarker potential for liquid biopsy. Methods: The expression of miR-34a was evaluated using quantitative real-time PCR in saliva samples from 9 patients with oral premalignant dysplastic lesions, 10 patients with OSCC and 10 healthy controls. The diagnostic accuracy of miR-34a expression profiles was assessed using ROC-curve analyses. Results: The expression of salivary miR-34a differed significantly across the studied groups, demonstrating a steep decrease in the presence of epithelial premalignant dysplasia, significant upregulation in OSCC and intermediate levels in normal oral mucosa (p < 0.001). The ROC results indicate strong diagnostic performance for the detection of oral dysplasia (AUC = 0.93; p < 0.001), OSCC (AUC = 0.77; p = 0.01) and excellent accuracy for the discrimination between premalignant and OSCC lesions (AUC = 0.98; p < 0.001). Conclusions: Our findings reveal a state-dependent dysregulation of miR-34a in oral carcinogenesis, suggesting its complex role as a pathogenetic agent that allows for malignant transformation through its diminished expression, and as a secondary reactive mechanism attempting to suppress tumor development. Salivary miR-34a holds great, stage-specific diagnostic potential, thereby reflecting the health state of oral mucosa in real time. Full article