Journal of the Egyptian National Cancer Institute最新文献

Background: The role of the complement system and its membrane-bound regulatory proteins (mCRPs) in the pathogenesis of cancer is still a debatable issue. The current study aimed to evaluate the role of the complement regulatory protein, the decay-accelerating factor (CD55), in the pathogenesis of acute leukemia.

Methods: CD55 gene expression was assessed in the peripheral blood of 34 patients with acute myeloid leukemia (AML), 26 patients with acute lymphoblastic leukemia (ALL), and 30 healthy controls by qRT-PCR. Also, CD55 gene knockdown was performed in HSB-2 (ALL cell line) using customized short hairpin RNA (shRNA). Flowcytometric analysis was done to ensure successful transfection, and MTT assay was performed to evaluate the cell viability post-transfection and silencing of CD55.

Results: There was a significant downregulation of CD55 in acute leukemia patients compared to the healthy controls (p < 0.001) with RQ values of AML, and ALL patients were 0.2499 ± 0.07427 and 0.2581 ± 0.09467, respectively. The MTT assay showed a significantly reduced viability of HSB-2 cells following posttranscriptional silencing of CD55 (p < 0.001) by 78.6% as compared to the non-transfected or mock-transfected cells. In the presence of human serum, there was a significant reduction in cell viability by 66.3% as compared to non-transfected controls (p = 0.01). Regarding the cells co-transfected with CD55 and CD46 silencing plasmids, cell viability was significantly decreased by 70.6% compared to non-transfected cells.

Conclusion: CD55 was significantly downregulated in acute leukemia. However, its in vitro silencing showed significant reduction in cell viability, giving it a dual opposing role in cancer.

Background: Microsatellite instability (MSI) and deficiency in the human mismatch repair (MMR) system are critical drivers of genomic instability in various cancers. Tumors exhibiting MSI and MMR deficiency (dMMR) have prognostic implications and are associated with differential responses to immune checkpoint inhibitors. Given their key roles in tumorigenesis, investigating MMR protein expression and MSI in urothelial cancer of the bladder is essential to improve therapeutic strategies and deepen understanding of its molecular features. This study aimed to assess MMR protein expression and MSI in primary urothelial carcinoma of the bladder and to evaluate their associations with clinicopathological characteristics.

Methods: A total of 49 primary urothelial carcinomas were analyzed for MMR expression using immunohistochemistry, and dMMR tumors underwent further analysis for MSI status using the markers of the Bethesda panel (BAT25, BAT26, D2S123, D5S346, and D17S250). The MMR expression and MSI findings were associated with clinicopathological parameters.

Results: dMMR was identified in two high-grade urothelial carcinomas (4.1%), while the remaining cases demonstrated proficient MMR. Both dMMR tumors showed impaired immunoreactivity, with one tumor displaying a simultaneous loss of the MLH1/PMS2 heterodimer and the other showing isolated MSH6 loss. MSI analysis revealed instability in BAT26 in the MLH1/PMS2-deficient tumor and at D17S250 in the MSH6-deficient tumor. Both tumors exhibited low-level MSI (MSI-L). No relevant associations were found between MMR/MSI status and clinicopathological features (p > 0.05).

Conclusions: The identification of MSI-L and MMR deficiency in only two samples underscores the rarity of MSI in urothelial carcinoma among Tunisian patients. These findings emphasize the need for larger, multi-center studies to elucidate the MSI/dMMR molecular and clinical implications in bladder carcinoma.

Colorectal cancer (CRC) is one of the most common tumors in the world. A recent area of study for the treatment of patients with solid tumors is anti-tumor immunity. PD-1/PD-L1 inhibitors were beneficial for cancer patients with multiple tumor types. However, their efficacy for CRC is low. Thus, there is an urgent need to explore additional co-inhibitory tools such as VISTA for CRC treatment.ObjectiveThe current study aimed to evaluate expression of VISTA on T cell subsets in patients with CRC and its correlation with other prognostic markers.Patients and methodsThe study included 31 patients with CRC and 25 healthy controls. All participants were subjected to full history taking, clinical examination, routine laboratory investigations, and flow cytometric detection of VISTA expression on T cell subsets on peripheral blood (PB). In addition to detection of VISTA expression on T cell subsets on tissue samples of both malignant CRC and normal colon tissue of the CRC patients.ResultsIn the peripheral blood, the expression of VISTA on CD4⁺ T helper and CD8⁺ T cytotoxic cells was significantly higher in CRC patients than the normal controls. There was no significant difference in VISTA expression on double positive T cells (CD4⁺CD8⁺) between the CRC patients and normal controls. In tissue samples, expression of VISTA on CD4 + T helper, CD8 + T cytotoxic, and double positive T (CD4 + CD8 +) cells in the malignant tissue of CRC patients was significantly higher than that in normal colonic tissue. Also, in CRC patients, the expression of VISTA on CD4⁺ T helper, CD8⁺ T cytotoxic, and double positive T cells in both malignant CRC tissue and normal colonic tissue was significantly higher than its expression PB.ConclusionThe higher expression of VISTA in CRC patients than the healthy controls and its higher levels in malignant CRC tissue and normal colonic tissue than PB of CRC patients suggest the role VISTA in the pathogenesis of CRC.

Background: The effectiveness of radioiodine therapy (RAI) in reducing recurrence and improving overall survival in differentiated thyroid carcinoma (DTC) remains debated. This systematic review evaluates the impact of RAI on DTC recurrence and survival.

Methods: A comprehensive search was conducted across PubMed, ScienceDirect, Web of Science, CINAHL, and Tripdatabase, including studies from inception to August 2024. Only studies published in English with full-text availability were included. Risk of bias was assessed using the Revised Risk of Bias Assessment Tool for Nonrandomized Studies of Interventions (RoBANS 2).

Results: Nine studies were included, involving 161,703 participants (36,658 men and 125,045 women). The studies were geographically diverse, with four from the American continent, three from Asia, and two from Europe. RAI doses ranged from 30 to 300 mCi, with 30 mCi and 100 mCi being the most common. Five studies found that RAI reduced recurrence, while two found no significant effect. The median time to recurrence ranged from 10 months to 15 years, with most studies indicating a 1-2-year median. Regarding overall survival, two studies reported improvement with successful RAI therapy, while two found no significant impact.

Conclusion: RAI therapy shows potential in reducing recurrence in DTC, particularly within the first 2-year post-treatment, but its effect on overall survival remains unclear. Further high-quality research is necessary to confirm these findings and guide clinical practice.

Background: Fibromas are common ovarian stromal tumors, while steroid cell tumors (SCTs) are rare, accounting for < 0.1% of ovarian neoplasms. Approximately, one-third of SCTs exhibit malignant behavior, but predicting malignancy remains challenging.

Case presentation: A 73-year-old woman presented with nonspecific pelvic pain, and imaging revealed multiple pelvic masses. She underwent a simple hysterectomy and bilateral adnexectomy. Pathological examination revealed a unique colocalization of a fibroma and a SCT in the right ovary. One year later, the SCT recurred with lymph node metastasis. Morphological analysis and whole exome sequencing suggested a shared origin for the fibroma and SCT components. Notably, two missense mutations in MUC4 were identified in the SCT, with immunohistochemistry confirming MUC4 overexpression. Steroidogenesis patterns in the SCT resembled those of adrenocortical carcinoma, indicating disorganized steroidogenesis and potentially explaining the absence of clinical endocrine abnormalities.

Conclusion: This case underscores the rarity and complexity of concomitant ovarian fibroma and malignant SCT. The identification of MUC4 mutations and disorganized steroidogenesis may provide insights into the pathogenesis of malignant SCTs. Further research is needed to understand the mechanisms and clinical implications of malignant SCT.

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.