Journal of the Egyptian National Cancer Institute最新文献

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.

Background: Triple-negative breast cancer (TNBC) is one of the most aggressive and formidable subtypes of breast cancer, devoid of targeted therapy and frequently leading to unfavorable prognoses and significant side effects. The demand for creative and effective treatment options has prompted the current study to investigate the potential of natural chemicals as therapeutic agents. This study intends to examine the efficacy of Galangin, a naturally occurring flavonoid, in treating triple-negative breast cancer.

Methods: The research utilizes a dual methodology, combining in silico network pharmacology with in vitro experimental methods. The in silico research proved crucial in finding significant gene targets and cellular signaling pathways influenced by Galangin in triple-negative breast cancer. To corroborate these computational predictions, a variety of in vitro studies were conducted, including the MTT assay, wound scratch assay, apoptosis assay, reactive oxygen species assay, mitochondrial membrane potential assessment, and RT-PCR.

Results: Fifteen prevalent genes were identified, demonstrating involvement in cellular proliferation, apoptosis regulation, cell migration, MAPK cascade regulation, and cell cycle regulation. The predominant genes implicated in the ten principal pathways were MAPK1, MAPK8, MAPK14, and IL6, which were observed to be linked to the MAPK signaling pathway, perhaps serving as the critical channel through which Galangin may facilitate the treatment of oral cancer. In vitro experiments demonstrated anti-proliferative effects, late-stage apoptosis, anti-migratory characteristics, antioxidant activity, and upregulation of the pro-apoptotic BAX gene.

Conclusion: This study's results demonstrate that Galangin possesses considerable anti-proliferative effects on TNBC cells, underscoring its potential as a viable therapeutic drug. These findings facilitate the development of more effective and precisely focused therapy approaches for TNBC, providing optimism for enhanced treatment outcomes for patients suffering from this challenging disease.

Background: Axillary lymph node dissection (ALND) is an essential step in the management of breast cancer. ALND is conventionally performed using radio frequency electrosurgery. The post-operative complications of utilizing such energy (such as prolonged drainage time, seroma, or infection) lead to prolonged recovery. Hence, it may delay the initiation of adjuvant chemo/radiotherapy for this critical category of patients. Using ultrasound shears provides a wide spectrum of tissue effects via mechanical oscillation. The absence of an electric circuit in ultrasound shears reduces thermal injury and accordingly cellular damage.

Objective: Comparing utilization of ultrasound shears in axillary lymph node dissection to conventional radio frequency electrosurgery in terms of operative time, post-operative drainage amount and days, post-operative pain, the incidence of seroma or infection, and lymph node yield.

Methods: This study is a randomized control trial. It includes 56 breast cancer ALND cases performed in conjunction with either BCS or MRM; being upfront surgery cases or post-neoadjuvant therapy cases, 28 patients underwent ALND using ultrasound shears and 28 underwent ALND using radio frequency electrosurgery.

Results: The mean age of the study population was 51 ± 11.7 years, with a mean BMI of 39. The mean operative time in the ultrasound shear group was 29.4. ± 7.6 min and 31.6 ± 5.1 min in the conventional group. The mean amount of drainage in the ultrasound shear group was 319.6 ± 75.4 ml and 407.5 ± 75.2 ml in the conventional group. The mean drainage days in the ultrasound shear group were 8 ± 1 day and 12 ± 2.2 days in the conventional group. Seroma formation was recorded in 6 of the ultrasound shear groups and 9 in the conventional group. Seroma followed by infection was found in 10% of the ultrasound shear group versus 21% in the conventional group. Seroma formation and wound infection were significantly related to the conventional group (p-value = 0.01).

Conclusion: Our study recommends the utilization of ultrasound shears in ALND as it is a safe and accurate method that allows faster post-operative recovery with shorter drainage time and lower incidence of seroma or infection, without affecting operative time or lymph node yield.

Trial registration: Trial no.: PACTR202402831197428. Date of approval: 19/02/2024.

Background: Severe oral mucositis (OM) is one of the adverse events post-chemotherapy, radiation, and stem cell transplantation with major clinical and economic impact. The management of severe OM remains challenging. This study aimed to look for the benefit and clinical impact of palifermin for mucositis among the non-transplanted pediatric cancer population.

Methods: This is a descriptive retrospective study extended from 2016 to 2020 at Prince Sultan Military Medical City (PSMMC), in Saudi Arabia. During this period all pediatric patients (< 14 years of age) on chemotherapy and complicated by severe OM that required palifermin (35 courses), as off-labeled medication, were analyzed looking for the clinical demographics, primary diagnosis, chemotherapy agents used, effectiveness, and tolerability of palifermin.

Results: A total of 29 patients with severe OM received 35 palifermin courses. All of them received 60 mcg/kg/day IV for 3 consecutive days. 20% of them have acute lymphoblastic leukemia (ALL). We noticed that 60% of severe OM required palifermin post anthracycline while high-dose methotrexate aggravates the risk in 40% of them. Only 25.7% of the patients required TPN for a median duration of 5 days and 54.3% of them received opioids for a median duration of 4 days. Twenty patients (57.1%) had used antibiotics, 4 patients were on antifungal medication and 1 patient was on anti-viral medication concomitant with antibiotics.

Conclusion: Palifermin is safe and well tolerated and shows some effect in non-hematopoietic stem cell transplant pediatric patients with severe oral mucositis post-intensified chemotherapy or radiation therapy.

Background: Head and neck sarcomas are very rare accounting for about 1% of head and neck malignancies and 5% of sarcomas. Outcomes have historically been worse in this group compared to other sarcomas, due to anatomical constraints that make complete surgical removal difficult and increased local relapse rate. Surgery remains the main intervention although the data suggest the role of chemotherapy and irradiation as treatment options.

Methodology: and Design. Data of patients diagnosed with head and neck sarcoma were retrospectively collected. Clinicopathologic characteristics and patients' management were reviewed. Time to relapse (TTR) includes both time to local relapse (TTLR) and time to systemic relapse (TTSR). Overall survival (OS), TTLR and TTSR were calculated with Kaplan Mayer analysis using log rank test.

Results: Twenty-four patients were retrospectively identified. Mean age was 37.7 years (range 17-80) with female gender predominance (62.5%). Rhabdomyosarcoma and osteosarcoma were the most common types (16.7%). At presentation, 23 patients showed localized disease (95.8%), while one patient was metastatic to the bone. Surgery was the primary treatment in 83.3% patients with different surgical margin status (R0 in 6/20, R1 in 11/20 and R2 in 3/20 patients), while 4/24 patients were not operated. Radiotherapy was applied as adjuvant treatment in 9 patients, as definitive in 2 and as palliative in one patient. Chemotherapy was administered in neoadjuvant/ adjuvant settings in 8 patients. Median follow-up was 31 months. Mean TTR for all surgically resected population was 39.8 months. Locally relapsed patients were 35% with mean TTLR 43.2 months while 15% of patients developed systemic relapse with mean TTSR 55 months. Mean OS of all studied patients was 48 months.

Conclusion: Head and neck sarcomas are rare challenging malignancies due to anatomical constrain, with only 20% achieving R0 surgical resection and > 30% suffering of local relapse after complete surgical resection.

Background: Podocytopenia refers to a decrease in the number of podocytes. When podocytes are injured, they may detach leading to podocytopenia, which represents a critical step in the development of podocytopathy and subsequently deterioration of renal functions. Pathological assessment of podocytopenia plays a crucial role in diagnosing underlying kidney diseases.

Aim: To assess detached podocytes and evaluate their diagnostic role in the development of focal segmental glomerulosclerosis.

Materials and methods: This is a retrospective study, conducted on 67 archival renal biopsies with the clinical diagnosis of steroid-resistant or steroid-dependent nephrotic syndrome (SRNS) and diagnosed as focal segmental glomerulosclerosis (FSGS) and podocytopathy with detached podocytes by electron microscopy (EM). Colloidal iron stain and Desmin immunohistochemical stain were performed. Assessment of the mean percent of stained pixels in relation to the surface tuft area of the glomerulus, i.e., mean percent of stained area (PSA) was done using image analysis system (ImageJ 1.52a) software.

Results: Podocytopathy with detached podocytes was diagnosed in 35 (52.24%) cases, while FSGS was diagnosed in 32 (47.76%) cases. Regarding detached podocytes, 27 (49.3%) cases showed no detached podocytes by light microscopy (LM), while only 4 (6%) showed severe podocyte detachment. There was a statistically significant difference between control cases and both podocytopathy with detached podocytes and FSGS regarding mean PSA (p ≤ 0.001).

Conclusion: Standardized reporting of detached podocyte cells is becoming mandatory as they have a high positive predictive value for the expected EM picture.

Functional genomics, a multidisciplinary subject, investigates the functions of genes and their products in biological systems to better understand diseases and find new drugs. Drug repurposing is an economically efficient approach that entails discovering novel therapeutic applications for already-available medications. Genomics enables the identification of illness and therapeutic molecular characteristics and interactions, which in turn facilitates the process of drug repurposing. Techniques like gene expression profiling and Mendelian randomization are helpful in identifying possible medication candidates. Progress in computer science allows for the investigation and modeling of gene expression networks that involve large amounts of data. The amalgamation of data concerning DNA, RNA, and protein functions bears similarity to pharmacogenomics, a crucial aspect in crafting cancer therapeutics. Functional genomics in drug discovery, particularly for cancer, is still not thoroughly investigated, despite the existence of a significant amount of literature on the subject. Next-generation sequencing and proteomics present highly intriguing opportunities. Publicly available databases and mining techniques facilitate the development of cancer treatments based on functional genomics. Broadening the exploration and utilization of functional genomics holds significant potential for advancing drug discovery and repurposing, particularly within the realm of oncology.

Glioblastoma multiforme (GBM) is the most common harmful high-grade brain tumor with high mortality and low survival rate. Importantly, besides routine diagnostic and therapeutic methods, modern and useful practical techniques are urgently needed for this serious malignancy. Correspondingly, the translational medicine focusing on genetic and epigenetic profiles of glioblastoma, as well as the immune framework and brain microenvironment, based on these challenging findings, indicates that key clinical interventions include immunotherapy, such as immunoassay, oncolytic viral therapy, and chimeric antigen receptor T (CAR T) cell therapy, which are of great importance in both diagnosis and therapy. Relatively, vaccine therapy reflects the untapped confidence to enhance GBM outcomes. Ongoing advances in immunotherapy, which utilizes different methods to regenerate or modify the resistant body for cancer therapy, have revealed serious results with many different problems and difficulties for patients. Safe checkpoint inhibitors, adoptive cellular treatment, cellular and peptide antibodies, and other innovations give researchers an endless cluster of instruments to plan profoundly in personalized medicine and the potential for combination techniques. In this way, antibodies that block immune checkpoints, particularly those that target the program death 1 (PD-1)/PD-1 (PD-L1) ligand pathway, have improved prognosis in a wide range of diseases. However, its use in combination with chemotherapy, radiation therapy, or monotherapy is ineffective in treating GBM. The purpose of this review is to provide an up-to-date overview of the translational elements concentrating on the immunotherapeutic field of GBM alongside describing the molecular mechanism involved in GBM and related signaling pathways, presenting both historical perspectives and future directions underlying basic and clinical practice.