Journal of the Egyptian National Cancer Institute最新文献

Chronic myeloid leukemia (CML) is a kind of leukemia that arises due to the translocation betwixt chromosomes 9 and 22. Philadelphia chromosome is characterized by the BCR::ABL fusion gene, which results from this recombination. It transcribes into active tyrosine kinase variants such as P185, P190, P210, and P230, depending on breakpoint chain variations. The fusion protein, encodes tyrosine kinases with varying exons, resulting in uncontrollable ATP-utilizing downstream signaling activities. Targeted therapy with various tyrosine kinase inhibitors (TKIs) is used to combat BCR::ABL fusion kinases and increase the survival rate of patients. However, the incidence of TKI resistance among CML patients is widely noticed around the world. Hence, an elaborate and accurate understanding of the structural interactions between BCR::ABL encoded tyrosine kinases, which are responsible for sensitivity and resistance, is mandatory for hassle-free targeted therapy. This review is intended to cover the reported structural interactions between BCR::ABL variants and TKI ligands in detail to highlight strategies that may be applied in the near future to overcome the resistance and other cross-reactions.

Introduction: Skin tumours comprise an important fraction of dermatology practice. Skin tumours can be benign or malignant, and patients can present with a merely unsightly nodule to a rapidly growing nodule. The diagnosis is made on pathological basis, which is done after performing skin biopsies.

Aim: In this study, we aim to describe the characteristics of malignant skin tumors diagnosed by skin biopsies over a one-year period (2023) at the Department of Dermatology, King Hussein Medical Center (KHMC).

Methods: In this retrospective study, data from biopsies that were done at our department and diagnosed as skin cancers were collected, patients' demographics were registered; including age, gender, and tumour location, and final diagnosis was recorded. Data was registered on an Excel® datasheet and analyzed using simple statistical methods.

Results: There were 78 biopsies that were diagnosed as skin cancers at the department of Dermatology. Of these, the most common diagnosis was basal cell carcinoma with 38% of the biopsied cancers. Eighteen per cent were diagnosed as squamous cell carcinomas, and 15% were melanomas. Mycosis fungoides and cutaneous T cell lymphoma cases were included in this study and reached 18% of the diagnosed skin cancers in our patients.

Accumulated evidence supported the crucial role of a tiny population of cells within the tumor called cancer stem cells (CSCs) in cancer origination, and proliferation. Additionally, these cells are distinguished by their self-renewal, differentiation, and therapeutic resistance capabilities. Interestingly, many studies recorded dysregulation of different types of noncoding RNAs, such as microRNA (miRNA) and long non-coding RNA (LncRNA), in cancer cells as well as CSCs. Moreover, several studies also supported the regulation of the transcription factors and signaling pathways required for CSC progression by these noncoding RNAs. However, the exact biological functions of all these noncoding RNAs are not well understood yet. These findings are of great interest, implying usage of noncoding RNA as therapeutic tool to target these cells. In this review, we provide an insight into how noncoding RNAs regulate CSCs and how this correlation is manipulated to develop new therapies to eradicate cancer cells successfully.

Background: Machine learning (ML) is a significant area of artificial intelligence, which can improve the accuracy of predictive or diagnostic models for differentiating between prostate biopsy outcomes. This study aims to develop a novel decision-support ML model for classifying patients with biopsy-negative (cancer-free), clinically significant, and non-clinically significant prostate cancer across two prostate-specific antigen (PSA) cut-offs ≤ 10 ng/ml and > 10 ng/ml.

Methods: The data for the current study were retrieved from the records of two main hospitals in Riyadh, Saudi Arabia from July 2018 through July 2024. Six machine learning algorithms were employed, and the dataset was randomly divided into a training set and a validation set at a ratio of 8:2. The following metrics were used as performance indicators across the six algorithms: Accuracy, Precision, Recall, F1-score, and area under the curve. Recent data from the two hospitals was utilized for external validation.

Results: The metrics for Random Forest, Extra Tree, and Decision Tree algorithms showed excellent capability in classifying the outcomes of prostate biopsy for the two PSA cut-offs. However, the metrics for the PSA cut-off > 10 ng/ml are higher than those for PSA ≤ 10 ng/ml. For the three-class classification, the accuracy and area under the curve for the cut-off > 10 ng/ml were 0.96 and 0.99, respectively. While for the cut-off ≤ 10 ng/ml they were 0.92 and 0.94 for Random Forest and 0.94 and 0.95 for the Extra Tree algorithm. The metrics of non-clinically significant and biopsy-negative cases outperformed those of clinically significant cases.

Conclusion: ML models are proving to be effective tools in differentiating between prostate biopsy outcomes, enhancing diagnostic accuracy, and potentially transforming clinical practices in prostate cancer management.

Background: To investigate the anticancer effects of 5-Fluorouracil (5-FU), thymoquinone (TQ), and/or coenzyme Q10 (CQ10), alone and combined, in HT29, SW480, and SW620 human colorectal cancer (CRC) cell lines.

Methods: Cell cycle progression and apoptosis were assessed by flow cytometry. Gene and protein expression of molecules involved in apoptosis (BLC2, survivin, BAX, Cytochrome-C, and Caspase-3), cell cycle (CCND1, CCND3, p21, and p27), the PI3K/AKT/mTOR/HIF1α oncogenic pathway, and glycolysis (LDHA, PDH, and PDHK1) were also analysed by quantitative RT-PCR and Western blot. Oxidative stress markers (ROS/RNS, MDA, and Protein carbonyl groups) and antioxidants (GSH and CAT) were quantified by ELISA.

Results: All treatments resulted in anticancer effects depicted by cell cycle arrest and apoptosis, with TQ demonstrating greater efficacy than CQ10, both with and without 5-FU. However, 5-FU/TQ/CQ10 triple therapy exhibited the most potent pro-apoptotic activity in all cell lines, portrayed by the lowest levels of oncogenes (CCND1, CCND3, BCL2, and survivin) and the highest upregulation of tumour suppressors (p21, p27, BAX, Cytochrome-C, and Caspase-3). The triple therapy also showed the strongest suppression of the PI3K/AKT/mTOR/HIF1α pathway, with a concurrent increase in its endogenous inhibitors (PTEN and AMPKα) in all cell lines used. Additionally, the triple therapy favoured glucose oxidation by upregulating PDH, while decreasing LDHA and PDHK1 enzymes. The triple therapy also displayed the most significant decline in antioxidant levels and the highest increases in oxidative stress markers.

Conclusions: This study is the first to demonstrate the superior anticancer effects of TQ compared to CQ10, with and without 5-FU, in CRC treatment. Moreover, this is the first report to reveal improved anticancer effects of the 5-FU/TQ/CQ10 triple therapy, potentially through promoting oxidative phosphorylation, attenuating the PI3K/AKT/mTOR/HIF1α pathway, and increasing oxidative stress-induced apoptosis.

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.