Journal of the Egyptian National Cancer Institute最新文献

Background: Recently, cancer treatment paradigms have shifted dramatically with the advent of immunotherapies, particularly chimeric antigen receptor (CAR) T-cell therapy. Despite it is revolutionary positive outcomes in treating hematologic malignancies, challenges such as severe toxicities, high treatment costs, and limited efficacy in solid tumors persist. This review highlights these limitations and the ongoing need for innovation in CAR T-cell therapy.

Main body: This manuscript provides a comprehensive review of most current advancements in CAR T-cell therapy, with a focus on targeting its immunotherapeutic principles, modification of T cells for Targeted cancer therapy using T cells, and clinical applications. It explores the key elements of CAR T-cell therapy, containing antigen recognition domain and intracellular signaling domains, which enable T cells to interact with cancer cells and exert cytotoxic effects. The review examines approved therapies, and ongoing clinical trials, Along with obstacles like cytokine release syndrome (CRS), neurotoxicity, along antigen escape mechanisms. Furthermore, innovations in cutting-edge CAR T-cell therapies and personalized treatment approaches are discussed, together with an emphasis on improving safety and efficacy.

Conclusion: The manuscript outlines the future outlook on integrating CAR T-cell therapy integrated with other treatments and exploring patient-specific approaches to revolutionize cancer care. This review aims to bridge the existing gaps in research, offering valuable insights for students and researchers in biomedical sciences and oncology.

Glioma is a devastating type of brain tumor with high malignancy, an extremely high mortality rate, and a recurrence risk. Molecular markers are known to have a major role in classification, prognosis, survival rate, and therapy determination for different glioma subtypes. The aim of this study was to investigate the association of gliomas' main genetic markers: isocitrate dehydrogenase (IDH) mutations and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status with the survival rate in Russian patients with glioblastoma and other glial tumors. According to histological subtype, included glioma patients were divided into two groups: glioblastoma (n = 90) and other gliomas (n = 40). IDH mutations were screened by high-resolution melting-curve analysis (HRM) followed by direct sequencing, and MGMT methylation was detected with pyrosequencing. Our data showed that IDH mutations are significantly more frequent among patients with other gliomas compared to glioblastoma patients (p < 0.001). Patients with mutated IDH gene have a significantly higher progression-free survival (PFS) and overall survival (OS) rates than those with wild-type genes. MGMT promoter methylation status was found to be significantly associated with PFS, but not OS. The presence of IDH mutation with a methylated MGMT promoter significantly increased patients' PFS and OS. To our knowledge, this is the first study to investigate the association of IDH and MGMT genetic biomarkers with glioma in the Russian population. Our findings could be used in future studies to improve glioma prognosis and classification and reach a personalized treatment protocols depending on multiple molecular biomarkers.

Background: Anaplastic thyroid carcinoma (ATC) is among the most lethal thyroid malignancies, with poor clinical outcomes and limited treatment strategies. To gain insights into the molecular mechanisms involved in its progression, we performed an integrative bioinformatic analysis.

Methods: We analyzed five microarray datasets from the GEO database to compare gene expression profiles between ATC samples and normal thyroid tissues. Differentially expressed genes (DEGs) were identified using GEO2R, and overlapping genes across datasets were detected through Venn diagram analysis. Functional enrichment was performed using DAVID and Metascape. A protein-protein interaction (PPI) network was constructed with STRING, and significant gene modules were identified using the MCODE plugin in Cytoscape. Co-expression analysis was further explored with GeneMANIA.

Results: We identified 7532 DEGs, of which 3509 were upregulated and 4023 were downregulated. Upregulated genes were mainly involved in cell division and mitotic control, while downregulated genes were related to thyroid hormone production and gland development. Six hub genes stood out for their centrality in the network: TPX2, MAD2L1, CDC20, CDKN3, CENPF, and NEK2.

Conclusion: Our findings shed light on key genes and pathways that may contribute to ATC pathogenesis. These results provide a foundation for identifying potential diagnostic biomarkers and therapeutic targets for this aggressive cancer.

Background: Blood stream infection (BSI) represent a life-threatening condition. Thus, we aimed to investigate the role of procalcitonin (PCT) and C-reactive protein (CRP) tests in adult febrile patients with BSI and other clinical infections in hospitalized cancer cases.

Methods: Blood culture (BC) testing was performed using BACTEC 9120. Identification and antibiotic susceptibility were done by Vitek 2®. Multiplex PCR for the detection of carbapenemases genes produced by Enterobacteriaceae was carried out including KPC, NDM, IMP, VIM, and Oxa-48 genes. Measurement of CRP was done via particle-enhanced immunoturbidimetric assay using Cobas C6000 autoanalyzer. PCT level was measured using the electrochemiluminescence immunoassay.

Results: Out of 101 febrile hospitalized adult cancer cases with clinical infection, 50 had positive BC, and 51 were positive for other infections (27 localized bacterial and 24 viral infections) with a negative BC. At a PCT cut-off value of 0.5 ng/mL, PCT median values were significantly higher in BSI patients than those with other infections (p = 0.004), specifically with gram-negative BSIs (p = 0.007). Higher PCT values were significantly related to ICU admission and poor response to therapy, p = 0.004 and 0.002, respectively. The difference in CRP values between patients with BSI and other febrile cases was not statistically significant, p = 0.922.

Conclusion: Higher PCT values were significantly related to blood stream infections, gram-negative pathogens, ICU admission, and poor response to therapy. Procalcitonin could be used to assign severity of infection and monitor response to antimicrobial therapy in high-risk patients, thus reducing days of antibiotics days.

Background: Male breast cancer is a rare disease that accounts for less than 1% of all cancers in men and less than 1% of all diagnosed breast cancers. We retrospectively evaluated clinicopathologic features, treatment options, and overall survival in male breast cancer cases over 10 years (2012-2021).

Methods: In this descriptive-cross-sectional study, the men with a breast cancer patient information based on demographic characteristics, type of surgery performed, pathological characteristics of samples (including the type of tumor involving lymph nodes and its grade), distant metastasis, immunohistochemical markers as well as family history of cancer, number of chemotherapy and radiotherapy sessions, use of anabolic drugs, and patient survival after surgery were recorded in the designed checklist.

Results: The results showed that the mean age of men with breast cancer was 56.14 ± 14.59. Invasive ductal carcinoma was diagnosed in 86.3% of patients. In addition, metastasis occurred in 23.5% of patients, and most metastases occurred in the liver and then in the bone marrow, respectively. The highest frequency was related to stage IIB, with a frequency of 29.4%. The overall survival rate of 1, 3, and 5 years for 51 cases was 96%, 91%, and 65%, respectively, with an average survival period of 96 months. There was a significant relationship between age, metastasis, and disease stage with the survival status of patients (P = 0.03).

Conclusions: In the present study, old age, higher stage, and metastasis in male breast cancer were associated with unfavorable survival.

Background: Lung adenocarcinoma (LUAD) is one of the main forms of carcinomas that contribute towards cancer-related mortality and morbidity. Identification of hub genes through various in silico approaches can lead to the successful prognosis of LUAD and may serve in reducing mortalities rising from it respectively.

Method: This research employs an integrated bioinformatics approach to uncover the molecular intricacies of LUAD. Utilizing the Gene Expression Omnibus (GEO) dataset, we identified GSE19188, GSE18842, GSE31210, and GSE19804 specific datasets from 423 LC tissues and 190 healthy tissues (controls). Differential gene expression analysis using GEO2R and Venn diagrams led to the identification of 851 differentially expressed genes (DEGs), comprising 240 overexpressed and 611 under-expressed genes. To elucidate their roles in LUAD etiology, we conducted protein-protein interaction (PPI) analysis utilizing Cytoscape and Cytohubba software's, revealing densely interconnected gene clusters with potential prognostic significance. Additionally, gene ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses were able to shed light on the involvement of these DEGs in processes such as cell cycle modulation and apoptosis, which are crucial in LUAD pathogenesis. Moreover, validation of the hub gene expression and their association with overall survival was performed using the University of Alberta Cancer Research Network (UALCAN) and Human Protein Atlas (HPA) databases, supporting our findings.

Results: The identified DEGs, including cyclin-dependent kinase-1 (CDK1), cyclin B2 (CCNB2), cell division cycle 20 (CDC20), BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B), cyclin A2 (CCNA2), discs-large associated protein 5 (DLGAP5), abnormal spindle microtubule assembly (ASPM), arrestin beta 1 (ARRB1), and caveolin-1 (CAV1), may serve as potential biomarkers for LUAD pathogenesis and should be explored further.

Conclusion: The present bioinformatics analysis enhances our understanding of molecular mechanisms contributing to LUAD and suggests that the hub genes identified could be promising targets for accurate diagnosis and novel therapeutic strategies in LUAD. Further investigations are necessary to validate and translate these findings into real-world clinical applications, paving the way for more effective treatments and improved outcomes in LUAD patients.

Background: Comparison of acute adverse events (acute skin reaction, acute breast pain and lung toxicities) in early-stage breast cancer using 2 different fractionation schedules: ultra-hypofractionation versus hypofractionation radiotherapy.

Methods: Ninety-two patients were recruited and assessed using RTOG criteria for acute skin reactions at the end of radiotherapy, 1 month after, and 3 months after.

Results: There have been no statistically significant differences in acute skin adverse events in 1 month after WBI, there have been neither G3 acute skin toxicity nor G2 skin reactions as were in the fast trial, and milder than skin adverse events in the FAST-FORWARD trial. Acute breast pain at the end of radiotherapy has been statistically significantly lower in arm 1 vs arm 2. Acute breast pain at 1-month follow-up has been comparable between the study arms, with no statistically significant difference. At the 3-month follow-up, acute breast pain was similar in both arms. In all arms, no acute lung toxicities have been reported.

Conclusion: Acute adverse events have been comparable between ultra-hypofractionation and hypofractionation.

Background: Recent statistical analyses indicate a rapid increase in the incidence of breast and colon cancer in Egypt. Although invasive techniques have been widely employed for early detection, diagnosis, and intervention of those cancers, they are associated with inherent risks and limitations, which often result in various complications. Therefore, noninvasive screening methods are inevitable due to their accessibility, cost-effectiveness, and high patient compliance rates. The enzyme L-asparaginase catalyzes the conversion of L-asparagine to L-aspartic acid: key metabolite for tumor cell division, thereby demonstrating anticancer potential. However, the prolonged use of bacterial L-asparaginase may cause allergic reactions and side effects such as diabetes, leukopenia, and co-agglutination disorders. Exploring the anticancer properties of L-asparaginase from different species such as yeast and fungi has been proposed to mitigate these adverse effects.

Objectives: This study aimed at extracting and optimizing the expression of L-asparaginase from the eukaryotic Cladosporium species, as to assess its anticancer potential against breast and colon cancer cell lines.

Method: Cladosporium species were identified morphologically and then cultured on modified Czapek-Dox Agar (mCDA) medium supplemented with L-asparagine to induce L-asparaginase production. Submerged fermentation was employed to optimize enzyme production. The enzyme activity was quantified using the Nesslerization method, and its cytotoxicity against colon and breast cancer cell lines was assessed using the (MTT) assay.

Results: Among the Cladosporium isolates, 18.4% exhibited positive plate assay test, with enzyme activities ranging from 255 to 428 U/mL. Immunoblotting using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed single protein band of approximately 37 kDa, consistent with L-asparaginase activity. Cytotoxicity assay of purified L-asparaginase showed significant antiproliferative effects against breast cancer cell lines MCF-7 and MDA-MB-231, with IC₅₀ values of 36.26 and 45.7 µg/mL, respectively.

Conclusion: Certain eukaryotic Cladosporium strains are potential sources for the anticancer L-asparaginase production.

Background: The cyclophospamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) regimen, a standard treatment for aggressive non-Hodgkin lymphoma (NHL), is effective but linked to chemotherapy-induced cardiotoxicity (CDIC), such as heart failure and left ventricular dysfunction. Anthracyclines like doxorubicin are key contributors to CDIC. This study examines left ventricular dysfunction and structural abnormalities in NHL patients receiving CHOP therapy with cumulative doxorubicin doses ≥ 250 mg/m², aiming to improve early CDIC detection and guide timely cardioprotective interventions.

Methods: This prospective cohort study was conducted at Dr. Soetomo Regional General Hospital, Surabaya, from June to October 2023. We included NHL patients aged 18-60 years at any stage, treated with CHOP regimens containing cumulative doxorubicin doses ≥ 250 mg/m², who completed at least four chemotherapy cycles, had baseline left ventricular ejection fraction (LVEF) ≥ 50%, and good echocardiographic window quality. Data were collected from medical records, biochemical tests, and echocardiography. Wilcoxon and paired T-tests were used for statistical analyses. The primary outcome was cardiac function, evaluated by reductions in LVEF, increased left ventricular strain, new structural abnormalities, and elevated high-sensitivity (HS) troponin and NT-proBNP levels post-chemotherapy.

Results: A total of 32 patients, aged 46.62 ± 16.64 years, were included, with the colli region and stage 2 NHL being the most common. Significant differences were observed in all parameters between pre- and post-chemotherapy. LVEF decreased by - 2.40% ± 1.79 (p < 0.001), while global longitudinal strain (GLS) declined by 2.25 ± 1.36 (p < 0.001). HS troponin I levels showed a significant increase of 17.27 ± 36.29 (p < 0.001), and NT-proBNP levels rose by 321.23 ± 85.34 (p < 0.001). The study also identified a higher risk of cardiotoxicity in patients over 50 years of age.

Conclusion: The CHOP regimen poses significant risks of subclinical cardiac dysfunction and structural abnormalities in NHL patients, with cumulative doxorubicin dosage being a key contributor. Early detection using sensitive biomarkers like GLS and NT-proBNP is crucial for identifying cardiotoxicity and enabling timely interventions.

Extracellular vesicles (EVs) have emerged as key cell-to-cell communication mediators and play significant roles in both physiological and pathological processes. In EVs, exosomes represent a distinct subpopulation of EVs that have been found to be involved in cancer initiation and therapeutic resistance. Exosomes transfer a diverse spectrum of molecular cargos that have significant effects on the tumor microenvironment (TME), thereby enabling cancer initiation, metastasis, and therapeutic resistance. Exosomes have recently been of interest in cancer therapy due to their role as important mediators of treatment resistance. The exosomal molecular content-proteins, miRNAs, and lncRNAs-allows exosomes to perform functions including drug efflux and detoxification, cell death pathway modulation, induction of epithelial-to-mesenchymal transition (EMT), and suppression of the immune system. In addition to facilitating immune and stromal cell interactions, exosomes cause extracellular matrix remodeling and induce tumor heterogeneity, making it more difficult to respond to therapy. This review covers intricate roles of exosomes in cancer therapy resistance with regard to their biogenesis, molecular content, and functional impact in the TME. Along with this, we also discuss new therapeutic strategies to overcome exosome-mediated resistance including utilizing exosome inhibitors, designed exosome therapy, and combination with conventional therapies. While exosomes hold promise in prediction and diagnosis through their biomarker function, their heterogeneous origins and cryptic functions make it difficult to target interventions. This review emphasizes that research on exosome-mediated pathways is urgently required to develop new therapeutic strategies that can improve cancer treatment outcomes.