Search Results (12,511)

Genomic integrity is critical for cellular homeostasis, preventing the accumulation of mutations that can drive diseases such as cancer. Among the mechanisms safeguarding genomic stability, the Base Excision Repair (BER) pathway plays a pivotal role in counteracting oxidative DNA damage caused by reactive oxygen species. Central to this pathway are enzymes like 8-oxoguanine glycosylase 1 (OGG1), which recognize and excise 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) lesions, thereby initiating a series of repair processes that restore DNA integrity. BER inhibitors have recently been identified as a promising approach in cancer therapy, increasing the sensitivity of cancer cells to radiotherapy and chemotherapy. By exploiting tumor-specific DNA repair dependencies and synthetic lethal interactions, these inhibitors could be used to selectively target cancer cells while sparing normal cells. This review provides a robust reference for scientific researchers, offering an updated perspective on small-molecule inhibitors targeting the 8-oxodG-BER pathway and highlighting their potential role in expanding cancer treatment strategies. Full article

Acquired resistance to chemotherapeutic drugs is the primary cause of treatment failure in the clinic. While multiple factors contribute to this resistance, increased expression of ABC transporters—such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance proteins—play significant roles in the development of resistance to various chemotherapeutics. We found that Erastin, a ferroptosis inducer, was significantly cytotoxic to NCI/ADR-RES, a P-gp-expressing human ovarian cancer cell line. Here, we examined the effects of both Erastin and RSL3 (Ras-Selected Ligand 3) on reversing Adriamycin resistance in these cell lines. Our results show that Erastin significantly enhanced Adriamycin uptake in NCI/ADR-RES cells without affecting sensitive cells. Furthermore, we observed that Erastin enhanced Adriamycin cytotoxicity in a time-dependent manner. The selective iNOS inhibitor, 1400W, reduced both uptake and cytotoxicity of Adriamycin in P-gp-expressing NCI/ADR-RES cells only. These findings were also confirmed in a BCRP-expressing human breast cancer cell line (MCF-7/MXR), which was selected for resistance to Mitoxantrone. Both Erastin and RSL3 were found to be cytotoxic to MCF-7/MXR cells. Erastin significantly enhanced the uptake of Hoechst dye, a well-characterized BCRP substrate, sensitizing MCF-7/MXR cells to Topotecan. The effect of Erastin was inhibited by 1400W, indicating that iNOS is involved in Erastin-mediated enhancement of Topotecan cytotoxicity. RSL3 also significantly increased Topotecan cytotoxicity. Our findings—demonstrating increased cytotoxicity of Adriamycin and Topotecan in P-gp- and BCRP-expressing cells—suggest that ferroptosis inducers may be highly valuable in combination with other chemotherapeutics to manage patients’ cancer burden in the clinical setting. Full article

Background/Objectives: Cold atmospheric plasma (CAP) has been demonstrated as an adjustable device to generate various combinations of short-lived reactive oxygen and nitrogen species (RONS) and as a promising appliance for cancer therapy. This study investigated the effects of direct and indirect treatments of Argon-based CAP to cancer cells (A2058, A549, U2OS and BCC) and fibroblasts (NIH3T3 and L929) on cell viability. We also aimed to understand whether plasma-generated RONS were involved in this process using genetic evidence. Methods: The intensity of reactive species in the plasma gas and the concentrations of RONS in phosphate-buffered saline (PBS) and cell culture medium were measured. A viability assay was performed after the cells were treated by plasma in PBS and medium with various volumes to realize the lethal effects of plasma under different conditions. Diverse cells were treated in the same solution to compare the sensitivities of different cells to plasma treatments. The gene expression profiles of A2058 cells after the direct and indirect treatments were analyzed by next generation gene sequencing. Accordingly, we discovered the advantages of sequential treatments on cancer therapy. Results: The cumulative concentration of hydroxyterephthalic acid (HTA) revealed that the pre-existing OH radical (•OH) in PBS increased with the treatment durations. However, there was no significant increase in the concentration of HTA in culture medium. HTA was detected in the treatment interface of PBS but not medium, showing the penetration of •OH through PBS. The concentrations of H₂O₂ and NO₂⁻ increased with the treatment durations, but that of NO₃⁻ was low. The direct treatments caused stronger lethal effects on cancer cells under certain conditions. The fibroblasts showed higher tolerance to plasma treatments. From gene expression analysis, the initial observations showed that both treatments influenced transcription-related pathways and exhibited shared or unique cellular stress responses. The pre-treatments, especially of direct exposure, revealed better cancer inhibition. Conclusions: The anti-cancer efficiency of plasma could be enhanced by pre-treatments and by adjusting the liquid interfaces to avoid the rapid consumption of short-lived RONS in the medium. To achieve better therapeutic effects and selectivity, more evidence is necessary to find optional plasma treatments. Full article

Recurrent tumors that are resistant to conventional chemotherapy are a major challenge of ovarian cancer treatment. A better understanding of the underlying molecular mechanisms of chemoresistance is critical for developing more effective targeted therapies for ovarian cancer. In this study, we analyzed the transcriptomic profiles of thirteen pairs of matching primary and recurrent ovarian cancers to identify genes that were upregulated in the recurrent tumors. Among these genes, we identified sortilin-related receptor 1 (SORL1) and its role in promoting carboplatin resistance through regulating the stability of epidermal growth factor receptor (EGFR) and fibroblast growth receptor 4 (FGFR4) using ovarian cancer models in vitro and in vivo. We further identified that an anti-SORL1 antibody inhibited the pro-tumor functions of SORL1. Our data showed that a selective inhibitor of FGFR4, FGF401, can improve the therapeutic efficacy of carboplatin in a xenograft mouse model of ovarian cancer. This study has demonstrated the therapeutic potential of targeting the SORL1/FGFR4 pathway to improve the chemoresponse of patients with recurrent and/or resistant ovarian cancer. Full article

The anticipated diagnosis of cancers and other fatal diseases from the simple analysis of the volatiles emitted by the body (volatolome) is getting closer and closer from becoming reality. The promises of vapour sensor arrays are to provide a rapid, reliable, non-invasive and ready-to-use method for clinical applications by making an olfactive fingerprint characteristic of people’s health state, to increase their chance of early recovery. However, the different steps of this complex and ambitious process are still paved with difficulties needing innovative answers. The purpose of this review is to provide a statement of the blocs composing the diagnostic chain to identify the improvements still needed. Nanocomposite chemo-resistive transducers have unique prospects to enhance both the selectivity and sensitivity to volatile biomarkers. The variety of their formulations offers multiple possibilities to chemical functionalization and conductive architectures that should provide solutions to discriminations and stability issues. A focus will be made on the protocols for the collection of organic volatile compounds (VOC) from the body, the choice of vapour sensors assembled into an array (e-nose), in particular, chemo-resistive vapour sensors, their principle, fabrication and characteristics, and the way to extract pertinent features and analyse them with suitable algorithms that are able to find and produce a health diagnosis. Full article

Background: Conventional treatments for cancers of the head and neck region are often associated with high recurrence rates and impaired quality of life. Photodynamic therapy (PDT) has emerged as a promising alternative, leveraging photosensitizers such as hypericin to selectively target tumour cells with minimal damage to surrounding healthy tissues. Objectives: We aimed to evaluate the efficacy and underlying mechanisms of hypericin-mediated PDT (HY-PDT) in treating head and neck cancers. Methods: Adhering to PRISMA 2020 guidelines, a systematic search was conducted across PubMed/Medline, Embase, Scopus, and the Cochrane Library for studies published between January 2000 and December 2024. Inclusion criteria encompassed preclinical in vitro and in vivo studies and clinical trials focusing on HY-PDT for head and neck malignancies and its subtypes. Results: A total of 13 studies met the inclusion criteria, comprising both in vitro and in vivo investigations. HY-PDT consistently demonstrated significant cytotoxicity against squamous cell carcinoma cells through apoptotic and necrotic pathways, primarily mediated by ROS generation. Hypericin exhibited selective uptake in cancer cells over normal keratinocytes. Additionally, HY-PDT modulated the tumour microenvironment by altering cytokine profiles, such as by increasing IL-20 and sIL-6R levels, which may enhance antitumor immunity and reduce metastasis. Conclusions: HY-PDT emerges as a highly promising and minimally toxic treatment modality for head and neck cancers, demonstrating efficacy in inducing selective tumour cell death and modulating the immune microenvironment. Despite the encouraging preclinical evidence, significant methodological variability and limited clinical data necessitate further large-scale, standardized and randomized controlled trials. Full article

Dysplastic nevi are skin lesions that have distinctive clinical features and are considered risk markers for the development of melanoma, the deadliest type of skin cancer. A specific deep learning technique to identify diseases is convolutional neural networks (CNNs) because of their great capacity to extract features and classify objects. Therefore, the research aims to develop a model to diagnose dysplastic nevi using a deep learning network whose classification is based on the pre-trained architecture EfficientNet-B7, which was selected for its high classification accuracy and low computational complexity. As for the results obtained, an accuracy of 78.33% was achieved in the classification model. Also, the degree of similarity between the detection by a dermatology expert and the proposed model reached an accuracy of 79.69%. Full article

The combination of molybdenum disulfide (MoS₂) with plasmonic nanomaterials has opened up new possibilities in biological applications by combining MoS₂’s biocompatibility and high surface area with the optical sensitivity of plasmonic metals. These MoS₂–plasmonic hybrid systems hold great promise in areas such as biosensing, bioimaging, and phototherapy, where their complementary properties facilitate improved detection, real-time visualization, and targeted therapeutic interventions. MoS₂’s adjustable optical features, combined with the plasmon resonance of noble metals such as gold and silver, enhance signal amplification, enabling detailed imaging and selective photothermal or photodynamic therapies while minimizing effects on healthy tissue. This review explores various synthesis strategies for MoS₂–plasmonic hybrids, including seed-mediated growth, in situ deposition, and heterojunction formation, which enable tailored configurations optimized for specific biological applications. The primary focus areas include highly sensitive biosensors for detecting cancer and infectious disease biomarkers, high-resolution imaging of cellular dynamics, and the development of phototherapy methods that allow for accurate tumor ablation through light-induced thermal and reactive oxygen species generation. Despite the promising advancements of MoS₂–plasmonic hybrids, translating these platforms into clinical practice requires overcoming considerable challenges, such as synthesis reproducibility, toxicity, stability in physiological conditions, targeted delivery, and scalable manufacturing. Addressing these challenges is essential for realizing their potential as next-generation tools in diagnostics and targeted therapies. Full article

Background: The role of molecular imaging in urothelial cancer is less defined than other cancers, and its utility remains controversial due to limitations such as high urinary tracer excretion, complicating primary tumour assessment in the bladder and upper urinary tract. This review explores the current landscape of PET imaging in the clinical management of urothelial cancer, with a special emphasis on potential future advancements including emerging novel non-¹⁸F FDG PET agents, PET radiopharmaceuticals, and PET-MRI applications. Methods: We conducted a comprehensive literature search in the PubMed database, using keywords such as “PET”, “PET-CT”, “PET-MRI”, “FDG PET”, “Urothelial Cancer”, and “Theranostics”. Studies were screened for relevance, focusing on imaging modalities and advances in PET tracers for urothelial carcinoma. Non-English language, off-topic papers, and case reports were excluded, resulting in 80 articles being selected for discussion. Results: ¹⁸F FDG PET-CT has demonstrated superior sensitivity over conventional imaging, such as contrast-enhanced CT and MRI, for detecting lymph node metastasis and distant disease. Despite these advantages, FDG PET-CT is limited for T-staging of primary urothelial tumours due to high urinary excretion of the tracer. Emerging evidence supports the role of PETC-CT in assessing response to neoadjuvant chemotherapy and in identifying recurrence, with a high diagnostic accuracy reported in several studies. Novel PET tracers, such as ⁶⁸Ga-labelled FAPI, have shown promising results in targeting cancer-associated fibroblasts, providing higher tumour-to-background ratios and detecting lesions missed by traditional imaging. Antibody-based PET tracers, like those targeting Nectin-4, CAIX, and uPAR, are under investigation for their diagnostic and theranostic potential, and initial studies indicate that these agents may offer advantages over conventional imaging and FDG PET. Conclusions: Molecular imaging is a rapidly evolving field in urothelial cancer, offering improved diagnostic and prognostic capabilities. While ¹⁸F FDG PET-CT has shown utility in staging, further prospective research is needed to establish and refine standardised protocols and validate new tracers. Advances in theranostics and precision imaging may revolutionise urothelial cancer management, enhancing the ability to tailor treatments and improve patient outcomes. Full article

Chimeric Antigen Receptor (CAR)-engineered T (CAR-T) cell therapy represents a highly promising modality within the domain of cancer treatment. CAR-T cell therapy has demonstrated notable efficacy in the treatment of hematological malignancies, solid tumors, and various infectious diseases. However, current CAR-T cell therapy is autologous, which presents challenges related to high costs, time-consuming manufacturing processes, and the necessity for careful patient selection. A potential resolution to this restriction could be found by synergizing CAR-T technology with the induced pluripotent stem cell (iPSC) technology. iPSC technology has the inherent capability to furnish an inexhaustible reservoir of T cell resources. Experimental evidence has demonstrated the successful generation of various human CAR-T cells using iPSC technology, showcasing high yield, purity, robustness, and promising tumor-killing efficacy. Importantly, this technology enables the production of clinical-grade CAR-T cells, significantly reducing manufacturing costs and time, and facilitating their use as allogeneic cell therapies to treat multiple cancer patients simultaneously. In this review, we aim to elucidate essential facets of current cancer therapy, delineate its utility, enumerate its advantages and drawbacks, and offer an in-depth evaluation of a novel and pragmatic approach to cancer treatment. Full article

Background/Objectives: Cancer is caused by disruptions in the homeostatic state of normal cells, which results in dysregulation of the cell cycle, and uncontrolled growth and proliferation in affected cells to form tumors. Successful development of tumorous cells proceeds through the activation of pathways promoting cell development and functionality, as well as the suppression of immune signaling pathways; thereby providing these cells with proliferative advantages, which subsequently metastasize into surrounding tissues. These effects are primarily caused by the upregulation of oncogenes, of which SPP1 (secreted phosphoprotein 1), a non-collagenous bone matrix protein, is one of the most well-known. Methods: In this study, we conducted a further examination of the transcriptomic expression profile of SPP1 (Osteopontin) during the progression of cancer in four human tissues, breast, prostate, renal and skin, in order to understand the circumstances conducive to its activation and dysregulation, the biological pathways and other mechanisms involved as well as differences in its splicing patterns influencing its expression and functionality. Results: A significant overexpression of SPP1, as well as a set of other highly correlated genes, was seen in most of these tissues, indicating their extensive implication in cancer. Increased expression was observed with higher tumor stages, especially in renal and skin cancer, while applying therapeutic modalities targeting these genes dampened this effect in breast, prostate and skin cancer. Pathway analyses showed gene signatures related to cell growth and development enriched in tumorigenic conditions and earlier cancer stages, while later stages of cancer showed pathways associated with weakened immune response, in all cancers studied. Moreover, the utilization of therapeutic methods showed the activation of immunogenic pathways in breast, prostate and skin cancer, thereby confirming their viability. Further analyses of differential transcript expression levels in these oncogenes showed their exonic regions to be selectively overexpressed similarly in tumorigenic samples in all cancers studied, while also displaying significant differences in exon selectivity between constituent transcripts, providing a basis for their high degree of multifunctionality in cancer. Conclusions: Overall, this study corroborates the entrenched role of SPP1 in the progression of these four types of cancer, as confirmed by its overexpression and activation of related oncogenes, their co-involvement in key cellular pathways, and predisposition to exhibit differential splicing between their transcripts, while the above effects were found to be highly inhibitable through treatment methods, thereby highlighting its promising role in therapeutic development. Full article

The colonoscopy procedure heavily relies on the operator’s expertise, underscoring the importance of automated polyp segmentation techniques in enhancing the efficiency and accuracy of colorectal cancer diagnosis. Nevertheless, achieving precise segmentation remains a significant challenge due to the high visual similarity between polyps and their backgrounds, blurred boundaries, and complex localization. To address these challenges, a Multi-scale Selective Edge-Aware Network has been proposed to facilitate polyp segmentation. The model consists of three key components: (1) an Edge Feature Extractor (EFE) that captures polyp edge features with precision during the initial encoding phase, (2) the Cross-layer Context Fusion (CCF) block designed to extract and integrate multi-scale contextual information from diverse receptive fields, and (3) the Selective Edge Aware (SEA) module that enhances sensitivity to high-frequency edge details during the decoding phase, thereby improving edge preservation and segmentation accuracy. The effectiveness of our model has been rigorously validated on the Kvasir-SEG, Kvasir-Sessile, and BKAI datasets, achieving mean Dice scores of 91.92%, 82.10%, and 92.24%, respectively, on the test sets. Full article

Background/Objectives: Neoadjuvant chemotherapy followed by concurrent chemoradiation therapy (NACT + CCRT) and adjuvant chemotherapy following CCRT (CCRT + ACT) have inconsistent effects on the survival of women with locally advanced cervical cancer (LACC) compared to CCRT. Moreover, the effects of NACT + CCRT and CCRT + ACT have not been clearly compared. This study compared the effects of NACT + CCRT and CCRT + ACT on survival using a network meta-analysis to select the optimal treatment in women with LACC. Methods: The PubMed, Medline, and Embase databases were searched, and six randomized controlled trials assessing the progression-free survival (PFS) and overall survival (OS) in women with newly diagnosed LACC treated with NACT + CCRT, CCRT + ACT, or CCRT alone (controls) were identified. A network meta-analysis was conducted. Results: Indirect comparisons showed no significant differences in PFS and OS between NACT + CCRT and CCRT + ACT. Direct comparisons also showed similar PFS and OS between NACT + CCRT and CCRT and between CCRT + ACT and CCRT. CCRT + ACT exhibited the highest surface under the cumulative ranking curve (SUCRA) value as a better treatment option for the PFS and OS (CCRT + ACT vs. NACT + CCRT vs. CCRT: 72% vs. 26.8% vs. 51.2% in PFS and 64.3% vs. 45.1% vs. 40.7% in OS). Conclusions: In women with LACC, NACT + CCRT had no different effects on the PFS and OS compared to CCRT + ACT, despite the relatively higher SUCRA value observed for CCRT + ACT. Further studies are warranted to clarify the effects of these strategies. Full article

Background/Objectives: Improved survival due to advances in medical therapy has resulted in increasing numbers of cancer patients living with bone metastases; however, our understanding of the prognostic implications of bone metastases requires larger population-based studies outlining their incidence and prevalence in different primary cancer types, including those with lower incidence. This study aimed to evaluate the incidence and prevalence of bone metastases in solid organ tumors by analyzing reports of staging CT studies with natural language processing (NLP). Methods: In this retrospective study, 639,470 reports representing 129,326 unique patients were analyzed; 6279 randomly selected reports were manually annotated and labeled for the presence or absence of bone metastases. From these data, a BERT-based NLP model was developed and applied to the patient database. The cumulative incidence at 5 years and prevalence of bone metastases in each cancer type were calculated. Results: The accuracy of the NLP model on a validation set was 97.1%, with a positive predictive value (precision) of 88.0% and a sensitivity (recall) of 86.3%. The 5-year incidence rate of bone metastases was highest in prostate, breast, head and neck, and lung cancer (52%, 41%, 36%, 33%). Incidence was lowest in central nervous system cancer and testicular cancer (8%, 5%). Prevalence was highest in prostate, breast, and lung cancer (32%, 25% and 23%), and lowest in central nervous system cancer and testicular cancer (4%, 4%). Conclusions: NLP was utilized to demonstrate patterns of bone metastases in a broad range of cancer types and is a valuable tool in population-based assessment of bone metastases. Full article

Colorectal cancer is a leading type of cancer worldwide and a major contributor to cancer fatalities, and liver metastasis is the most likely distant metastasis in colorectal cancer patients. Classifying and predicting whether liver metastasis occurs in colorectal cancer patients can help doctors timely determine the progress of the disease and form a more reasonable treatment plan, which results in a better prognosis for patients. In this paper, using the Surveillance, Epidemiology, and End Results database, selecting both symmetric and asymmetric features, we extracted the disease-related data of 40,870 patients who were pathologically diagnosed with colorectal cancer from 2010 to 2015 and classified and modeled whether the patients developed liver metastasis to show the symmetry of this study. A total of six deep learning models were utilized, and hyperparameter optimization was performed on the models using the Crested Porcupine Optimizer. The best-performing model was selected and model interpretation was performed to explore the features that affect whether patients develop liver metastasis. Among the six deep learning models selected, the FT-Transformer model, which was hyperparameter optimized by the Crested Porcupine Optimizer, performed the best, with an accuracy of 0.945, with a 95% confidence interval (CI) of [0.942, 0.952], and an AUC of 0.949, with a 95% CI of [0.942, 0.957]. This study can help doctors make medical decisions, detect patients with liver metastases of colorectal cancer earlier, monitor the indicators that have a significant impact on the occurrence of liver metastasis in patients, and use timely surgical treatment, radiotherapy, chemotherapy, and other corresponding therapeutic interventions to improve the survival rate of patients. Full article