Journal of the Egyptian National Cancer Institute最新文献

Background: Hodgkin lymphoma (HL) is a highly curable malignant tumor. Risk-adapted treatment for children with HL aims to maximize survival while minimizing toxicity. The purpose of this study is to evaluate the outcome and prognostic characteristics of Egyptian pediatric HL patients treated at the National Cancer Institute (NCI), Cairo University.

Methods: All newly diagnosed cases of classic HL treated between January 2016 and December 2018 were included in this study.

Results: The median age at initial presentation was 8 years in 69 eligible individuals, with a male-to-female ratio of 4.7:1. Eighteen percent of patients had an elevated erythrocyte sedimentation rate (ESR) of more than 50, 42% had more than three lymph node (LN) group involvements, 18.8% had bulky disease, 52.2% were at an advanced stage, and 34% had B symptoms. Age  > 15 years, B symptoms,  > 3 LN group involvement, extra-nodal disease, and advanced stages significantly affected the overall survival rate (OS) (P-values = 0.03, 0.033, 0.008, 0.017, and 0.032). There was no statistically significant difference between patients who got combined modality therapy (CMT) and those who received chemotherapy alone (3-year OS and event-free survival (EFS) were 95.5% and 87.6% vs. 89.9% and 83.3%, P-values of 0.70 and 0.90). Patients with an interim-negative positron emission tomography-computed tomography (PET-CT) had a 3-year OS of 94.7%, compared to 74.1% in patients with an interim-positive PET-CT (P = 0.06), suggesting that rapid early response (RER) is a significant prognostic factor. There was no statistically significant survival difference between patients with a negative interim PET-CT who got CMT and those who received chemotherapy alone (3-year OS and EFS: 100% and 88.2% vs. 95% and 90%; P = 0.35 and 0.70, respectively). Three-year OS was 93.3% and 100%, and EFS was 74.3% and 100% (P = 0.495 and 0.196%) for those who got 15 Gy versus those who received 20 Gy or more, respectively. At the end of the study, the OS and EFS at 3 years for the whole group were 91.9% and 83.6%.

Conclusion: Treatment with risk- and response-adaptive treatment should be the standard of care for treating pediatric patients with HL.

Background: Breast cancer is the most common tumor among women throughout the world. Diagnosis and treatment of breast cancer are associated with stress and depression. Self-efficacy is one of the most important personal characteristics, studied in cancer, and is correlated with depression and immunity. The aim of the study is as follows: 1. Examining the correlation between coping self-efficacy with depression, DHEA levels, and immunity 2. Examining the correlation between depression and DHEA levels 3. Studying the effect of depression and DHEA levels on immunity 4. Examining the intermediate effect of DHEA levels on the correlation between coping self-efficacy and immunity METHODS: Thirty newly diagnosed breast cancer patients recruited from the Oncology Department, Kasr EL-Aini, Cairo University (ages 51.40 + 8.24 years) responded to two questionnaires: Coping Self-Efficacy Scale (CSES) and Patient Health Questionnaire-9 (PHQ-9); blood samples were collected to measure the phenotype of patients' cellular immunity and DHEA levels by flowcytometry and ELISA technique.

Results: There was a significant negative correlation between CSES and PHQ-9, a significant positive correlation between PHQ-9 and B-cell count, and there is a significant negative correlation between CSES and B-cell count. The presence of DHEA has no mediatory role on correlation between CSES and B-cell count.

Conclusion: This paper presents a new model of psychoneuroimmunology by suggesting an effect of coping self-efficacy on immunity against breast cancer patients.

Hypoxia arises due to insufficient oxygen delivery to rapidly proliferating tumour cells that outpace the available blood supply. It is a characteristic feature of most solid tumour microenvironments and plays a critical role in regulating anti-tumour immunity, enhancing tumoral heterogeneity, and promoting therapeutic resistance and poor clinical outcomes. Hypoxia-inducible factors (HIFs) are the major hypoxia-responsive transcription factors that are activated under low oxygenation conditions and have been identified to drive multifunctional roles in tumour immune evasion. The HIF signalling network serves as an attractive target for targeted therapeutic approaches. This review aims to provide a comprehensive overview of the most crucial mechanisms by which HIF controls the expression of immunosuppressive molecules and immune checkpoints, disrupts cancer immunogenicity, and induces immunotherapeutic resistance.

Aims: Both S100A4 and Glypican-3 have been known to be engaged in HCC development and progression. This study aimed to evaluate both S100A4 and GPC3 expression in HCC tissues as a prognostic markers.

Methods: Tissues from 70 patients of HCC in cirrhotic HCV patients were evaluated by immunohistochemistry using antibodies against SA100A4 and GPC3 and compared with tumor-adjacent tissue (controls). All cases were followed for 40 months.

Results: GPC3 was more expressed in HCC (79%) than S100A4 (21%). S100A4 was more significantly expressed in cases showing metastasis, microscopic vascular emboli, necrosis, and grade III tumors. There was no relationship between overall survival and both S100A4 and GPC3. The only significant independent predictor for recurrence was decompensation (OR 3.037), while metastasis was significantly predicted by S100A4 expression (OR 9.63) and necrosis (OR 8.33).

Conclusion: S100A4 might be used as a prognostic marker for HCC, while GPC3 is a reliable marker of HCC diagnosis.

Background: The huge number of detected somatic KIT mutations highlights the necessity of in silico analyses that are almost absent in the relevant medical literature. The aim of this study is to report the mutation spectrum analysis of exon 11 encoding the juxtamembrane (JM) domain of the KIT gene in a group of Syrian GIST patients.

Methods: Forty-eight formalin-fixed paraffin-embedded GIST tissue samples, collected between 2006 and 2016, were retrieved from the pathological archives and analyzed for KIT exon 11 mutations by DNA sequencing. Structural/functional impact of detected variants was predicted using several bioinformatic tools.

Results: Twenty-one different variants have been detected in intron 10, exon 11, and intron 11 of the KIT gene, eight of which were novel changes. Mutations in exon 11 of the KIT gene were detected in 28 of 48 (58.3%) GIST patients and predicted to be pathogenic and cancer promoting. Specifically, age above 60 was very significantly associated with the negative selection of deletion mutations (p = .007), a phenomenon that points to deletion severity.

Conclusions: Six bioinformatic tools have proved efficient in predicting the impact of detected KIT variations in view of published structural, experimental, and clinical findings.

Background: Breast cancer is the most common tumor among females globally. Its prevalence is growing around the world, and it is alleged to be the leading cause of cancer death. Approved anti-breast cancer drugs display several side effects and resistance during the early treatment stage. Hence, there is a need for the development of more effective and safer drugs. This research was aimed at designing more potent quinazolin-4(3H)-one molecules as breast cancer inhibitors using a ligand-based design approach, studying their modes of interaction with the target enzyme using molecular docking simulation, and predicting their pharmacological properties.

Methods: The QSAR model was developed using a series of quinazoline-4(3H)-one derivatives by utilizing Material Studio v8.0 software and validated both internally and externally. Applicability domain virtual screening was utilized in selecting the template molecule, which was structurally modified to design more potent molecules. The inhibitive capacities of the design molecules were predicted using the developed model. Furthermore, molecular docking was performed with the EGFR target active site residues, which were obtained from the protein data bank online server (PDB ID: 2ITO) using Molegro Virtual Docker (MVD) software. SwissADME and pkCSM online sites were utilized in predicting the pharmacological properties of the designed molecules.

Results: Four QSAR models were generated, and the first model was selected due to its excellent internal and external statistical parameters as follows: R² = 0.919, R²_adj = 0.898, Q²_cv = 0.819, and R²_pred = 0.7907. The robustness of the model was also confirmed by the result of the Y-scrambling test performed with cR²p = 0.7049. The selected model was employed to design seven molecules, with compound 4 (pIC₅₀ = 5.18) adopted as the template. All the designed compounds exhibit better activities ranging from pIC₅₀ = 5.43 to 5.91 compared to the template and Doruxybucin (pIC₅₀ = 5.35). The results of molecular docking revealed better binding with the EGFR target compared with the template and Doruxybucin. The designed compounds exhibit encouraging therapeutic applicability, as evidenced by the findings of pharmacological property prediction.

Conclusions: The designed derivatives could be utilized as novel anti-breast cancer agents.

Objective: Immunohistochemical expression of P53 protein is so closely related to status of mutation of P53 gene which is tightly linked with pathogenesis of nephroblastoma or Wilms tumor. This study aims to determine the immunohistochemical expression of P53 protein and its predictors in formalin-fixed paraffin-embedded tissue blocks of patients with nephroblastoma.

Materials and methods: A series of 83 histologically diagnosed cases of nephroblastoma from formalin-fixed paraffin-embedded tissue blocks archived at the Department of Pathology, Makerere University, in Kampala, Uganda, were analyzed. Monoclonal anti-p53 antibody (DO-7, DAKO) was used to assess the expression of P53 protein expression. Multivariable logistic regression analysis was performed to determine the predictors of P53 protein immunohistochemical expression, and statistical significance was considered when p-value was less than 0.05.

Results: Most (42.2%, n = 35) of the cases were in advanced tumor stages (III-V), and almost one-quarter (21.7%, n = 18) of the cases were in high-risk group. The immunohistochemical expression of P53 protein was (8.4%, n = 7), and there were more (83.3%, n = 5) positive anaplastic cases for P53 protein compared with (2.6%, n = 2) of P53 expression for non-anaplastic cases. High risk (AOR = 3.42, 95% CI = 7.91-12.55, p = 0.037) and anaplasia (AOR = 1.41, 95% CI = 13.85-4.46, p = 0.001) were potential predictors of immunohistochemical expression of P53 protein.

Conclusion: Most of patients with nephroblastoma in resources-limited settings are diagnosed with advanced clinical stages. Association of P53 protein with anaplasia found in this study indicates the possibility of having novel target therapy for treatment of patients with anaplastic form of nephroblastoma with a focus of identifying molecules that lead to its suppression in such subpopulations of patients with nephroblastoma.

Background: Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system tumors. GBM patients usually have a poor prognosis. Identification of genes associated with the progression of the disease is essential to explain the mechanisms or improve the prognosis of GBM by catering to targeted therapy. It is crucial to develop a methodology for constructing a biological network and analyze it to identify potential biomarkers associated with disease progression.

Methods: Gene expression datasets are obtained from TCGA data repository to carry out this study. A survival analysis is performed to identify survival associated genes of GBM patient. A gene co-expression network is constructed based on Pearson correlation between the gene's expressions. Various topological measures along with set operations from graph theory are applied to identify most influential genes linked with the progression of the GBM.

Results: Ten key genes are identified as a potential biomarkers associated with GBM based on centrality measures applied to the disease network. These genes are SEMA3B, APS, SLC44A2, MARK2, PITPNM2, SFRP1, PRLH, DIP2C, CTSZ, and KRTAP4.2. Higher expression values of two genes, SLC44A2 and KRTAP4.2 are found to be associated with progression and lower expression values of seven gens SEMA3B, APS, MARK2, PITPNM2, SFRP1, PRLH, DIP2C, and CTSZ are linked with the progression of the GBM.

Conclusions: The proposed methodology employing a network topological approach to identify genetic biomarkers associated with cancer.

Background: The purpose of this study was to assess the usefulness of fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET)-computed tomography (CT) scan for staging urinary bladder cancer. The study also sought to determine the effect of ¹⁸F-FDG PET/CT on management decisions and its implications for patient care.

Methods: A total of 133 patients with bladder cancer who had both conventional imaging and ¹⁸F-FDG PET/CT for initial staging were identified. All ¹⁸F-FDG-PET/CT findings were classified as true positive, true negative, false positive, or false negative based on their potential to impact the intent of treatment. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated using the standard definition. Furthermore, the rate of change in therapy intent was determined for the entire sample and for subgroups with non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) patients.

Results: The overall concordance rate between PET/CT and conventional imaging was around 54%. On conventional images, 18% of patients had localized disease, which was upstaged in 6.8% of cases using ¹⁸F-FDG PET/CT. Pelvic lymph node involvement was detected in 18.8% of cases using conventional imaging, which was downstaged to localized disease in 4.5% of cases using ¹⁸F-FDG PET/CT. While 63.2% of patients had systemic disease on a CT scan, 24.7% of cases were downstaged using PET/CT. Overall, the rate of change in therapy intent was 26.3% for the entire sample, 24.5% for NMIBC subgroup, and 27.3% for MIBC patients.

Conclusions: The study found that ¹⁸F-FDG PET/CT is an effective and accurate tool for staging bladder cancer in newly diagnosed patients. Approximately one quarter of patients had a change in management intent based on ¹⁸F-FDG PET/CT results. The study suggests that PET/CT should be used as a standard for newly diagnosed patients, but more research is needed to confirm this.

Background: In the Ugandan setting, investigation for PHNM with CT uses a protocol with both unenhanced and contrast enhanced procedures hence doubling the ionizing radiation exposure. The purpose of this study was to determine the feasibility of single CT procedures in diagnosing PHNM.

Methods: This was a cross-sectional study using CT images from patients, aged fifteen years and below, investigated for head and neck malignancies at the Uganda Cancer Institute. Three radiologists, observers A, B and C, with 12, 5 and 2 years of experience, respectively, participated in the study. They independently reported contrast enhanced images (protocol A), unenhanced images (protocol B), then both unenhanced and contrast enhanced images (protocol C) in 2 months intervals. Inter- and intra- observer agreement was determined using Gwen's Agreement coefficient.

Results: Seventy-three CT scans of 36 boys and 37 girls, with a median age of 9 (3-13) years, were used. Intra-and inter-observer agreement on primary tumour location ranged from substantial to almost perfect with the highest intra-observer agreement observed when protocols A and C were compared. Inter-observer agreement for tumour calcifications was substantial for protocol A. Observers A and C demonstrated an almost perfect intra-observer agreement when protocols A and C were compared. There was a substantial inter-observer agreement on diagnosis for all protocols.

Conclusions: In our setting and examining a limited number of CT images, we demonstrated that contrast-enhanced CT scans provide sufficient information with no evidence of additional value of unenhanced images. Using contrast-enhanced images alone reduced the radiation exposure significantly.