Journal of the Egyptian National Cancer Institute最新文献

The significance of gut bacteria and their byproducts is gaining greater recognition, especially in the realm of immunotherapy. An imbalance in gut bacteria or their byproducts is intricately linked to the onset, progression, and treatment of cancer. Metabolites derived from gut microbiota, including short-chain fatty acids (SCFAs), secondary bile acids (SBAs), indole derivatives, and trimethylamine oxide (TMAO), engage with cellular targets to initiate intracellular signaling pathways. These signals are conveyed to the cell, influencing its growth. Targeted therapies encompass a complex and ever-evolving area that is crucial in cancer management. Nonetheless, it is vital to recognize that targeted therapy encounters a multitude of challenges. Factors influencing the success of targeted therapy include drug resistance resulting from prolonged use, side effects, and variations in genetic mutations, tumor diversity, and the complex nature of the tumor microenvironment. Recently, we have deepened our understanding of the relationship between the gut microbiome and anticancer targeted therapies. This is one face of the molecular pathologic epidemiology. This prompts us to investigate promising treatment strategies linked to these gut bacteria and their metabolites, thereby unlocking new possibilities for targeted anticancer therapies.

Background: Whole-genome sequencing has enabled the development of a wide range of analytical tools to search for abnormalities associated with tumors. As classic myeloproliferative neoplasms (MPNs) are associated with genomic alterations in hematopoietic stem cells, the World Health Organization (WHO) recommendations include since 2008 molecular investigations as an important part of the diagnosis and management of these pathologies. Recent advances in sequencing technologies, such as next-generation sequencing (NGS), have enhanced the analysis platforms. However, epidemiological information on MPNs is limited, especially in low/middle-income countries.

Aim: This literature review provides a state-of-the-art on the classification of MPNs and a comprehensive examination of contemporary analytical techniques, while highlighting the advantages and drawbacks of each method.

Methods: The scientific literature for the synthesis of this article was obtained by searching the PubMed and Science Direct databases, and the tables were generated using Excel 2016 software.

Results: Driver mutations in MPNs can be detected by genotyping or sequencing. Genotyping techniques present an increased risk of false negatives because of their low sensitivity, whereas sequencing techniques are more sensitive but can present specificity or time-consuming disadvantages.

Conclusion: Although a large number of applications favor NGS, it is essential to consider the cost-effectiveness of these technologies to meet the needs of laboratories in low/middle-income regions. Alternative techniques such as real-time polymerase chain reaction (qPCR), immunohistochemistry (CAL2IHC), and liquid chromatography (dHPLC) should be explored and considered as sustainable options.

Background: The convergence of biology and nanomaterials has propelled technological progress in biomedical sciences, offering transformative applications in diagnostics and therapy. Among these advancements, quantum dots (QDs) semiconductor nanocrystals activated by light have emerged as versatile tools due to their unique optical and electronic properties. Graphene quantum dots (GQDs), a subset of QDs, are nanoscale fragments of graphene that exhibit exceptional features, making them highly suitable for innovative biomedical applications. These include cancer detection, drug delivery, and imaging, areas where early diagnosis and effective treatment are crucial.

Main body: The production of synthetic GQDs relies on two primary approaches: top-down methods, where larger carbon structures are broken into smaller fragments, and bottom-up methods, which involve assembling GQDs from smaller molecular units. Both methods offer advantages depending on the desired properties and applications of the GQDs. GQDs possess several beneficial characteristics, including high photostability, excellent biocompatibility, and tunable fluorescence, which make them particularly valuable for biomedical purposes. In cancer therapy, GQDs serve as efficient nano-delivery vehicles for drugs, offering enhanced targeting and reduced side effects compared to traditional chemotherapy. Furthermore, their fluorescence properties enable precise imaging and early detection of cancerous cells, providing a dual functionality in diagnosis and therapy. Current research highlights advancements in QD synthesis techniques, enhancing their scalability and application potential. These innovations underscore the role of GQDs in bridging the gap between experimental research and clinical applications.

Conclusion: Quantum dots, particularly graphene quantum dots, represent a breakthrough in the field of nanomedicine. Their synthesis, functional properties, and dual roles in diagnostics and therapeutic delivery underscore their importance in advancing cancer treatment and early detection. With continued research and development, GQDs are poised to revolutionize drug delivery systems and expand the horizons of biomedical science.

Background: Precision medicine has transformed oncology by tailoring treatments to the molecular and genetic characteristics of individual tumors. Stem cell-based strategies hold unique potential to complement these approaches by enabling regenerative support, targeted delivery of therapeutics, and novel models for drug screening.

Methods: This review synthesizes current evidence on the integration of stem cell biology into precision cancer therapy, highlighting advances in tumor profiling, next-generation sequencing (NGS), and genome editing that enable personalized interventions.

Results: Emerging applications include engineered stem cells for selective delivery of oncolytic agents, immune modulation through stem cell-derived platforms, and the use of induced pluripotent stem cells (iPSCs) for modeling tumor heterogeneity. Advances in NGS are accelerating tumor-specific profiling, facilitating gene editing of stem cells, and refining patient selection for therapy.

Challenges: Despite progress, translational barriers remain, including risks of tumorigenicity, ethical concerns, high costs, immune rejection, and limited large-scale clinical validation.

Conclusion: Stem cell-based precision oncology is a rapidly evolving field with significant promise. Future directions include integrating NGS-driven tumor profiling with engineered stem cells, optimizing safety through gene-editing technologies, and advancing clinical trials to establish efficacy. These efforts could reshape the landscape of individualized cancer care.

Long non-coding ribonucleic acids (LncRNAs) are larger than 200 nucleotides and resemble messenger ribonucleic acids (mRNAs), but they do not code for proteins. In both cell development and physiological cell function, LncRNAs have crucial biological functions. Consequently, cancer entails the disruption of their biological function. Many people die from lung cancer because it is diagnosed late, spreads to other parts of the body, and has a high treatment failure rate. Because they can be involved in either oncogenic or tumor-suppressing functions, LncRNAs are quickly becoming core molecules in lung cancer. Since LncRNAs are long-lasting in blood, they can be utilized as non-invasive diagnostic tools for cancer at an early stage. We review the latest research that has brought together evidence from real-world observations concerning the processes through which LncRNAs work in cancer formation, how they allow cancer to develop drug resistance, and how they can be used as possible diagnostic tools and markers of outcome, with a focus on lung cancer. We also cover some of the ongoing treatment strategies that can target LncRNAs. As seen from what has been laid out here, the examination of LncRNAs in lung cancer with protein-coding genes could provide evidence for a further elucidation of the molecular events behind the disease as well as its progression, and the potential for a new therapeutic pathway.

This study primarily aims to investigate the effects of gamma (γ) radiation, both independently and in combination with zinc oxide nanoparticles (ZnO NPs), on normal and lung cancer cell lines. Lung cancer continues to be a major cause of cancer-related mortality globally. Radiotherapy is a common way of treating lung cancer. The treatment efficacy of cell death requires a high dosage of focused radiation. Due to their physicochemical properties and potential biological activity, ZnO NPs have emerged as promising candidates in nanomedicine and oncology. In this research, ZnO NPs were synthesized and characterized through various analytical techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), differential scanning calorimetry (DSC), and dynamic light scattering (DLS). The resulting nanoparticles were semi-spherical in shape (22-29 nm), stable, and had a zeta potential of - 21 ± 2.40 mV. The cytotoxic effects were assessed using human lung cancer cells (A549) and normal lung fibroblast cells (WI-38). Treatments involved ZnO NPs alone or combined with 15 Gy of γ-radiation over 48 h. A significant increase in cytotoxicity was observed in A549 cancer cells compared to normal cells. ZnO NPs alone showed moderate anticancer efficacy with an IC50 of 26.78 ± 0.44 µg/mL, whereas ZnO NPs + 15 Gy gamma radiation led to a pronounced reduction in cell viability with an IC50 of 15.97 ± 0.45 µg/mL. These results indicate that the combination of ZnO NPs with γ-radiation enhances apoptosis and significantly suppresses the growth of lung cancer cells (p < 0.001), offering potential for improved therapeutic outcomes in lung cancer radiotherapy.

Background: Methotrexate (MTX) is a commonly prescribed drug with both chemotherapeutic and immunosuppressive applications. However, when administered in high doses (HDMTX ≥ 500 mg/m²), it can lead to serious side effects, particularly nephrotoxicity and hepatotoxicity. Although 48-h MTX levels monitoring is fundamental for the evaluation of the risk of these toxicities, the relationship between MTX level and the actual clinical outcomes is not yet fully addressed. This study aims to evaluate the predictors of 48-h serum MTX levels and the toxicity profile associated with patients receiving HDMTX for management of cancer, with a particular focus on nephrotoxicity, hepatotoxicity, length of hospital stay (LOS), antimicrobial use, and 30-day mortality.

Methods: A retrospective cohort study was conducted at the National Cancer Institute, Cairo University. Patients receiving HDMTX as part of their cancer treatment in the period from January 2022 to December 2024 were included. Data collection included patient demographics, administered MTX doses, 48-h serum MTX levels, medical and medication history, antimicrobials used, and recorded adverse effects. The outcome of the study encompassed the identification of predictors for 48-h MTX levels and their association with acute kidney injury (AKI), ICU admission, and LOS. In addition to the associations with hepatotoxicity, antimicrobial usage, and mortality. Statistical analysis was performed using SPSS version 26.0.

Results: Among 143 patients, elevated 48-h MTX levels (≥ 1.28 μmol/L) were associated with pleural effusion (P-value 0.038), patients diagnosed with lymphoma (P-value 0.05), and increased antimicrobial use (P-value < 0.05). A significant association was found between HDMTX and the use of carbapenems, vancomycin and fluoroquinolones (P-value < 0.05). Non-significant relation was found between HDMTX and AKI as well as LOS. Hepatotoxicity was significantly more common in patients with osteosarcoma rather than hematological malignancies, while LOS was shorter in osteosarcoma cases compared to hematological malignancies.

Conclusion: The serum levels of 48-h MTX are vital metrics of toxicity, as they determine the duration of hospitalization, the number of antimicrobials used, and the mortality rate. Thus, it is crucial to monitor these levels to reduce the complications associated with HDMTX usage.

Background: Pancreatic cancer stands among the most aggressive and fatal malignancies, with a steadily increasing incidence worldwide. Its clinical significance lies not only in its high mortality rate but also in the challenges associated with its early detection, limited therapeutic efficacy, and substantial impact on healthcare systems. The asymptomatic nature of the disease in its initial stages, combined with the absence of reliable early biomarkers, contributes to frequent late-stage diagnoses, significantly compromising treatment success and patient survival. Furthermore, the biological complexity of pancreatic tumors - often marked by specific genetic mutations and a highly immunosuppressive tumor microenvironment - drives resistance to conventional therapies, exacerbating clinical management difficulties.

Main body: This narrative review offers a comprehensive synthesis of the major therapeutic challenges and recent advances in pancreatic cancer management over the past fifteen years. The main challenges include delayed diagnosis, the presence of treatment-resistant tumor subtypes, and the considerable financial burden of care. Particular attention is given to the tumor microenvironment, which impedes drug delivery and immune system activation due to its dense fibrotic stroma and immunosuppressive cellular composition. The review also explores emerging therapeutic strategies, including combination chemotherapy regimens such as folinic acid, fluorouracil, irinotecan, and oxaliplatin, and advanced radiotherapy techniques that aim to enhance precision while minimizing tissue damage. Furthermore, novel immunotherapeutic approaches - including messenger RNA-based vaccines and engineered cellular therapies - show promising results in stimulating targeted immune responses, although they face substantial barriers due to the tumor's immune evasion mechanisms. Targeted therapies focused on specific genetic alterations, especially those involving KRAS mutations, are also highlighted as potential breakthroughs. The review concludes by emphasizing the relevance of personalized medicine, with biomarker-driven strategies and three-dimensional tumor models offering more tailored and potentially effective interventions.

Conclusion: Despite meaningful progress in the development of innovative therapeutic modalities, pancreatic cancer continues to present profound medical and scientific challenges. Integrating personalized, interdisciplinary approaches and advancing early diagnostic tools remain essential steps toward improving clinical outcomes and extending survival in affected patients. This review underscores the urgent need for continued research to transform current insights into effective and accessible treatment strategies.

The field of cancer immunotherapy has evolved rapidly, offering new treatment paradigms by harnessing the body's own immune system to target and destroy malignancies. Various immunotherapeutic approaches, including immune checkpoint inhibitors, CAR-T cell therapy, cancer vaccines, cytokine therapies, and oncolytic viruses, have shown significant promise in treating different cancer types. This review provides a comprehensive examination of the historical development and recent advances in cancer immunotherapy. We discuss the mechanisms of action of key immunotherapeutic modalities, along with their clinical applications and innovative delivery techniques. In particular, we focus on immune checkpoint inhibitors, which have revolutionized the treatment of several cancers; CAR-T cell therapy, which has provided transformative results in hematological malignancies; and the potential of cancer vaccines, cytokine therapies, and oncolytic viruses. Additionally, the review addresses the current status of clinical trials and patents in the field, offering insight into the ongoing efforts to optimize these therapies for broader clinical use. Despite the promising results achieved, this review highlights significant challenges, such as immune-mediated toxicity, resistance to treatment, and the need for more effective delivery systems. While cancer immunotherapy has shown great potential in improving patient outcomes, overcoming existing obstacles such as toxicity and resistance remains a major challenge. This review offers a comprehensive overview of the state of cancer immunotherapy while also providing perspectives on its future directions and the ways in which these innovations may impact cancer treatment.