Journal of the Egyptian National Cancer Institute最新文献

Non-small cell lung cancer (NSCLC) is a prevalent and lethal malignancy worldwide, posing significant challenges to patient survival. Recent advancements in the field of oncology have introduced immunotherapy and targeted therapy as primary treatment modalities for NSCLC. However, the emergence of treatment resistance and relapse has impeded their long-term effectiveness. Antibody-drug conjugates (ADCs), a rapidly evolving class of anti-cancer agents, offer a promising solution to this issue by harnessing the specificity of monoclonal antibodies and the cytotoxic potency of drug payloads. ADCs have demonstrated notable potential in targeting both highly expressing and low-expressing malignant cells, with early-phase clinical trials yielding superior survival outcomes in NSCLC patients. This review comprehensively outlines the recent advancements in ADC-based strategies for managing NSCLC, supported by evidence from clinical trials. Additionally, the review delves into the oncogenic mechanisms of various biomarkers and offers insights into strategies for their detection in NSCLC patients. Lastly, a forward-looking perspective is provided to address the challenges associated with the utilization of ADCs in NSCLC therapy.

Background: Breast cancer (BC) is a malignant tumor characterized by a high incidence rate and is the leading cause of cancer-related deaths among women worldwide. This study aims to identify key genes and potential prognostic biomarkers using a bioinformatics approach.

Methods: Three microarray datasets, GSE86374, GSE120129, and GSE29044, were downloaded from the GEO database. GEO2R and Venn diagram software were employed to identify differentially expressed genes (DEGs), while DAVID was utilized for functional enrichment analysis. Subsequently, STRING and Cytoscape were used to construct the protein-protein interaction (PPI) network among the DEGs. UALCAN, GEPIA, and the Kaplan-Meier plotter were employed for prognostic analysis. Following this, the correlations and alterations of key genes were examined using cBioPortal. Finally, immunohistochemistry (IHC) was performed to validate the expression levels of the key genes.

Results: A total of 323 differentially expressed genes (DEGs) were identified. From the protein-protein interaction (PPI) network, 37 hub genes were selected. Validation using UALCAN, GEPIA, and Kaplan-Meier plotters revealed that three key genes-RACGAP1, SPAG5, and KIF20A-were significantly overexpressed and associated with poor prognosis in breast cancer (BC), as well as advanced tumor staging. The correlations and alterations of these key genes, as demonstrated on cBioPortal, indicated that their alterations co-occurred. Experimental verification through immunohistochemistry (IHC) confirmed that the proteins of these key genes were highly expressed in tumor tissues.

Conclusions: The key genes identified in this study can enhance our understanding of the molecular mechanisms underlying breast cancer (BC). Additionally, these genes may serve as potential sensitive biomarkers for patients with BC.

Background: Busulfan at high doses has been associated with a risk of seizures. Phenytoin has been used traditionally as anti-seizure prophylaxis, and benzodiazepines and levetiracetam have been introduced more recently, providing data from retrospective series. The main purpose of this study was to evaluate the effectiveness of oral clonazepam as anti-seizure prophylaxis in adult patients receiving high doses of intravenous busulfan as part of the conditioning regimen for hematopoietic stem cell transplantation. The secondary objectives were to determine the feasibility of this regimen and to analyze the adverse events associated with the use of clonazepam.

Methods: This prospective, single-center study included 64 adult patients who received conditioning regimens with high doses of intravenous busulfan and anti-seizure prophylaxis with oral clonazepam, at a dose of 1 mg/8 h, from 12 h before starting treatment with busulfan until 48 h after ending administration.

Results: The effectiveness of the prophylaxis was 100%, with no episodes of seizures during busulfan treatment or in the 72 h afterwards. Treatment was feasible, and oral scheduled administration was completed in all patients. Adverse events that could be associated with clonazepam included the onset of somnolence, dizziness, and confusion, mostly mild.

Conclusion: The oral clonazepam regimen described in this study has been prospectively shown to be an effective, feasible anti-seizure prophylaxis option with manageable toxicity.

Objectives: To evaluate central quadrantectomy and nipple resection with areola preservation (CQ-NR-AP) as a new reconstructive oncoplastic technique Versus Grisotti flap mammoplasty (GFM) in central malignant tumors of the breast extending to the nipple, in terms of time procedures, breast symmetry, patient satisfaction, postoperative complications, and local recurrence.

Patients and methods: The current study is a single-blind, single-center, randomized, controlled trial that was performed between May 2018 and May 2023 in the breast surgery unit of University Hospitals. This trial involved 40 individuals who had central breast lesions that extended to the nipple and were monitored for two years following surgery.

Results: As regards the mean intra-operative time in minutes, in the group (I) was 80.1 with a standard deviation of ± 13.9, and ingroup (II) was 138.9 with a standard deviation of ± 14.02 (p = 0.001). The seroma was detected in zero cases in group (I) and 2(10%) cases in group II (p = 0.487) and those two cases were managed by aspiration only. Regarding, the wound infection was found in one case (5%) in group (I) and 3(15%) cases in group II (p = 0.605). Regarding patient satisfaction and breast, symmetry was much better in the group (I).

Conclusion: The safety and ease of central quadrantectomy and nipple resection with areola preservation were demonstrated in a two-year follow-up, with a lower incidence of complications compared to the Grisotti flap mammoplasty technique. Furthermore, this approach was associated with higher patient satisfaction, which is a significant achievement in the management of centrally located breast tumors.

Trial registration: PACTR202405688323721. 28/05/2024.

Background: Colorectal cancer (CRC) is a major public health concern. Animal models play a crucial role in understanding the disease pathology and development of effective treatment strategies. Chemically induced CRC represents a cornerstone in animal model development; however, due to the presence of different animal species with different genetic backgrounds, it becomes mandatory to study the susceptibility of different mice species to CRC induction by different chemical entities such as 1,2-dimethylhydrazine (DMH). This study aimed to investigate the induction receptivity of two commonly used mice species, C57BL/6 and BALB/c, to DMH-induced CRC.

Methods: Both mice species were exposed to weekly intraperitoneal injections of DMH at a dose of 20 mg/kg body weight for 15 consecutive weeks. The response to DMH was evaluated by monitoring body weight gain, daily food intake, and gastrointestinal symptoms. At the end of exposure, histopathology of distal colon dissected from both species was analyzed.

Results: Results revealed that C57BL/6 had a higher response to DMH compared to BALB/c. A significant decrease in body weight gain concomitant with severe diarrhea was observed in C57BL/6 receiving DMH compared to their controls, without any difference in food intake. Histopathology of distal colon revealed aberrant crypt foci and loss of goblet cells in DMH-exposed C57BL/6 mice. On the other hand, BALB/c mice displayed a normal and intact colon, with a normal weight gain pattern, and without any gastrointestinal symptoms.

Conclusion: In conclusion, C57BL/6 has a higher susceptibility toward chemical induction to CRC; therefore, it can be used to study CRC pathogenesis, prevention, and treatment.

Introduction: Silver nanoparticles (AgNPs) derived from natural sources have garnered significant attention due to their unique properties and eco-friendly production methods. With lung cancer remaining a major global health issue, there is a continuous need for novel and effective therapeutic approaches beyond conventional treatments such as chemotherapy, immunotherapy, and targeted therapies.

Objective: This study aims to synthesize AgNPs using plant extracts from Gymnema sylvestre, Moringa oleifera, and Azadirachta indica and to evaluate their anticancer activity, particularly their effects on gene expression in A549 lung cancer cells.

Methods: AgNPs were synthesized using green chemistry techniques and characterized by X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). Gene expression studies were performed to assess the impact of AgNPs on cancer-related genes such as VEGF and CYCLIN-D1. Cytotoxicity assays were conducted on A549 cells to determine the anticancer potential of the synthesized AgNPs compared to plant extracts alone.

Results: XRD confirmed the formation of crystalline AgNPs, while FTIR indicated the presence of bioactive compounds interacting with the nanoparticles. Gene expression analysis revealed significant downregulation of VEGF and CYCLIN-D1, suggesting inhibitory effects on angiogenesis and cell cycle progression. The synthesized AgNPs exhibited potent cytotoxic activity against A549 cells, with enhanced efficacy compared to the leaf extracts alone.

Conclusion: The study highlights the potential of AgNPs synthesized from medicinal plant extracts as promising candidates for lung cancer therapy. Their environmentally sustainable production, combined with their ability to target key cancer pathways, positions them as innovative and affordable therapeutic agents in the field of nanomedicine.

Background: Green synthesis techniques have drawn a lot of interest lately since they are beneficial to the environment and have potential uses in a variety of industries, including biomedicine. Because of their special physicochemical characteristics, copper nanoparticles (CuNPs) have become one of the most interesting options for use in biological applications among nanomaterials. An overview of green synthesis methods for CuNPs is given in this review, along with a discussion of their applications in cancer therapeutics. The benefits and drawbacks of certain green synthesis techniques, such as plant-mediated, microorganism-mediated, and other environmentally friendly processes, are discussed. Moreover, a thorough discussion is given of CuNPs' biological uses, including their antibacterial activity, anticancer potential, drug transport, and bioimaging capabilities. Furthermore, difficulties and prospects for the application of green-synthesised CuNPs in biomedicine are discussed.

Objective: Meningiomas are a molecularly ill-defined heterogeneous group of indolent intracranial tumors. Though, WHO grade 1 tumors are histologically benign, sometimes they transform into malignant and may be recurrent which remains always challenging to clinicians. Therefore, the current study sought to discover the clinical relevance of CD44 in meningioma patients.

Method: Protein expression of CD44 was investigated using immunohistochemistry in a total of 70 meningioma patients. Immunoscore performed using modified H-score, CD44 expression correlated with clinicopathological parameters and progression-free survival (PFS) and overall survival (OS). Univariate and multivariate survival analysis was analyzed. The data was evaluated using SPSS statistical software and P-value ≤ 0.05 was considered as significant.

Results: The membranous and cytoplasmic protein expression of CD44 was noted in meningioma tumors. Based on H-score, the weak (0-190 score) and strong (191-300 score) immunoreactivity was observed in 62.9% and 37.1% of patients, respectively. A statistically significant positive correlation was found between strong CD44 expression and WHO grade 2/3 tumors (χ² = 33.551, r = + 0.692, P = 0.0001), and with the presence of brain invasion (χ² = 19.521, r = + 0.528, P = 0.001). In Kaplan-Meier univariate survival analysis for PFS and OS, apart from WHO grade of tumors (PFS; log-rank = 12.309, P = 0.0001, OS; log-rank = 17.830, P = 0.0001) and brain invasion status (PFS; log-rank = 11.941, P = 0.001, OS; log-rank = 13.554, P = 0.0001) CD44 expression (PFS; log-rank = 14.942, P = 0.0001, OS; log-rank = 20.986, P = 0.0001) remained significant prognostic factor for PFS and OS. In multivariate survival analysis, at step 1, only CD44 remained independent prognosticator for PFS (HR = 11.014, 95% CI = 2.256-23.602, P = 0.001) and OS (HR = 8.553, 95% CI = 2.831-25.847, P = 0.0001). In relation to treatment offered, patients with strong CD44 expression and if treated with surgery followed by adjuvant radiotherapy showed a high incidence of death (log-rank = 13.402, P = 0.0001) as compared to patients treated with surgery only. Receiver operating characteristic (ROC) curves also confirmed a good efficacy of CD44 as a prognosticator for disease outcome (PFS; P = 0.0001, OS; P = 0001).

Conclusion: Our overall findings addressed that a study of CD44 protein expression would be beneficiated to meningioma patients from unnecessary overtreatment and drug-induced toxicity. Also, CD44 could be one of the promising biomarkers that might differentiate high-risk meningioma patients for better treatment management.

Background: Tumor recurrence or metastasis after surgery is a significant factor influencing bladder cancer (BC) prognosis. Novel molecular biomarkers are necessary to determine each patient's specific outcome because current biomarkers have limited power for predicting prognosis. The proto-oncogene MET encodes c-MET, a tyrosine kinase receptor. When c-MET attaches to its ligand, it triggers several steps in the signal transduction cascade that control cell survival, proliferation, and invasion. c-MET is overexpressed in several carcinomas. The HER2 gene encodes another receptor tyrosine kinase (RTK). HER2 overexpression is linked to altered proliferation and increased aggressiveness in several malignancies. Identifying crosstalk partners of RTKs implicated in bladder cancer development may have a unique role in predicting aggressiveness. This study explored the expression status of c-MET and HER2 in human BC and their clinical significance in disease outcomes.

Methods: A quantitative real-time polymerase chain reaction was done on 40 BC patients who had undergone transurethral resection (TUR) or radical cystectomy and had a pathologically verified diagnosis of primary tumor without prior chemoradiotherapy as well as 20 patients with benign diseases who served as controls. The c-MET and HER2 expression levels were investigated, and their relationship with clinicopathological features was analyzed.

Results: c-MET and HER2 gene expression were significantly higher, 6.1- and 4.5-fold, in the study group compared to the controls. The frequency of c-MET and HER2 overexpression in the study group was 80% (32/40) and 90% (36/40), respectively. c-MET overexpression was associated with pathological stage(P = 0.002), tumor grade (P = 0.019), muscle invasion (P = 0.008), and node involvement (P = 0.017), while HER2 overexpression was associated with pathological stage(P = 0.033), invasion to muscles (P = 0.003), and node involvement (P = 0.005). Based on the Log-rank test, patients expressing both c-MET and HER2 had the poorest disease-free survival rates among all studied patients (median = 10 m, 3.0-16.9 95%CI).

Conclusion: There is a possible correlation between c-MET and HER2 gene overexpression and poor clinical outcomes in patients with BC.

Background: Lung cancer is a form of cancer that is responsible for the largest incidence of deaths attributed to cancer worldwide. Non-small cell lung cancer (NSCLC) is the most prevalent of all the subtypes of the disease. Treatment with tyrosine kinase inhibitors (TKI) may help some people who have been diagnosed with non-small cell lung cancer. The presence of actionable mutations in the epidermal growth factor receptor (EGFR) gene is a key predictor of how a patient will respond to a TKI. Thus, the frequency of identification of mutations in EGFR gene in patients with NSCLC can facilitate personalized treatment.

Objective: The objective of this study was to screen for mutations in the EGFR gene and to investigate whether there is a correlation between the screened mutations and various clinical and pathological factors, such as gender, smoking history, and age, in tissue samples from patients with NSCLC.

Methods: The study comprised 333 NSCLC tissue samples from 230 males and 103 females with an average age of 50 years. Exons 18-21 of the EGFR gene have been examined using real-time PCR. Using SPSS, correlations between clinical and demographic variables were examined, and EGFR mutation and clinical features associations were studied.

Results: The study's findings revealed that the incidence rate of EGFR mutation was 24.32% (81/333), with partial deletion of exon 19 (19-Del) and a point mutation of L858R in exon 21 accounting for 66.67% (P < 0.001) and 28.40% (P < 0.001) of the mutant cases, respectively. Patients who had the T790M mutation represent 4.94% (P = 0.004) of total number of patients. Females harbored EGFR mutations (54.32%) with higher frequency than men (45.68%) (P < 0.001), while nonsmokers had EGFR mutations (70.37%) more frequently than current smokers (29.63%) (P < 0.001).

Conclusion: The screening study conducted in Egypt reported that the EGFR mutations prevalence was 24.32% among Egyptians with NSCLC. The study also found a slight gender bias, with females having an incidence rate of these mutations higher than males. Additionally, nonsmokers had higher rates of mutations in EGFR gene compared to smokers. According to the findings, somatic EGFR mutations can be employed as a diagnostic tool for non-small cell lung cancer in Egypt, and they can be implemented in conjunction with clinical criteria to identify which patients are more likely to respond favorably to TKIs.