Journal of the Egyptian National Cancer Institute最新文献

Triple-negative breast cancer (TNBC) is among the most difficult subtypes of breast cancer to treat and is characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. Owing to its Limited molecular targets and high degree of tumor heterogeneity, TNBC is associated with poor prognosis and restricted treatment options. Exosome small extracellular vesicles secreted by virtually all cell types have gained renewed attention for their role in tumor progression, metastasis, immune modulation, and drug resistance in TNBC. These vesicles carry biologically active cargo such as proteins, RNAs, Lipids, and metabolites that reflect the molecular state of their parent cells and facilitate intercellular communication. However, conventional 2D culture systems and classical exosome isolation methods fail to replicate the complexity of the tumor microenvironment and the diversity of exosomal populations. This review summarizes recent advances in the integration of three-dimensional (3D) culture systems and advanced chromatographic techniques to enhance the isolation, profiling, and functional analysis of TNBC-derived exosomes. We highlight the benefits of using 3D models, improvements in analytical workflows, and interdisciplinary approaches that are enabling progress in biomarker discovery, understanding therapy resistance, and developing exosome-based therapeutic strategies. By bridging technological innovation with biological insight, this review aims to support future advances in exosome research relevant to TNBC.

Background: This research aimed to explore if carnitine (CARN) deficiency is a risk factor in methotrexate (MTX)-mediated acute kidney injury (AKI) and to mechanistically reveal the potential attenuating effect of CARN against MTX-mediated nephrotoxicity.

Methods: Thirty-six adult male Wister albino rats were subgrouped into six groups. Groups 1, 2, and 3 received 0.9% normal saline (0.5 mL/200 g, i.p.), mildronate (MD, 200 mg/kg/day, i.p.), and L-carnitine (CARN, 200 mg/kg/day, i.p.) for 10 uninterrupted days, respectively. Groups 4, 5, and 6 received similar doses of normal saline, MD, and CARN for 5 days prior to as well as following a solo dose of methotrexate (MTX, 20 mg/kg, i.p.), respectively.

Results: Treatment with a single dose of MTX significantly boosted serum nephrotoxicity as well as hepatotoxicity indices; additionally, it increased the percentage of collagen deposition in rat kidney tissues with obvious histopathological changes. Moreover, MTX lowered kidney levels of adenosine triphosphate (ATP) and amplified acetyl-CoA carboxylase-1 (ACC-1) in kidney tissues. In MD-treated rats, MTX progressively boosted nephrotoxicity indices and collagen disposition in kidney tissues as well as progressive additional reduction in ATP as compared with MTX-treated rats and serum carnitine levels compared with MD-treated rats. Carnitine administration totally counteracted the biochemical and histopathological alterations mediated by MTX to the normal measures.

Conclusions: This research proposes that carnitine deficiency is a potential risk factor in the development of MTX-mediated AKI. MTX disrupts ACC1 signaling with the consequential inhibition of ATP production. Carnitine supplementation attenuates MTX-mediated AKI. Our results are preliminary and mandate further mechanistic study to justify the progression of AKI by MTX in CARN-deficient rats.

Purpose: This study sought to investigate the prevalence and sociodemographic determinants related to breast and cervical cancer screening among ever-married women aged 15 to 49 years in Jordan.

Methods: This research employed secondary data from the 2023 Jordan Population and Family Health Survey (JPFHS), which included 12,547 ever-married women aged 15 to 49. Weighted multivariable logistic regression analyses were conducted to quantify screening prevalence and identify related covariates, presented as adjusted odds ratios (AORs) with 95% confidence intervals (CIs).

Results: The prevalence of screening for breast and cervical cancer was 15.2% and 16.2%, respectively. Increased screening participation was substantially correlated with advanced age, larger home affluence, higher parity, previous sexually transmitted infections (STIs), and exposure to radio communications. Women aged 35-49 were more likely to receive breast (AOR: 4.0; 95% CI: 2.6-6.0) and cervical cancer screening (AOR: 5.5; 95% CI: 3.3-9.2) compared to those aged 15-24 years. Women in the highest wealth quintile had a greater likelihood of being screened for breast cancer (AOR: 2.1; 95% CI: 1.6-2.8) and cervical cancer (AOR: 2.6; 95% CI: 1.9-3.5). Moreover, breast cancer screening correlated with recent healthcare service consumption (AOR: 1.3; 95% CI: 1.1-1.6), while cervical cancer screening had a favorable association with elevated educational attainment (AOR: 1.6; 95% CI: 1.2-2.3). Living in rural areas was inversely correlated with cervical screening participation (AOR: 0.7; 95% CI: 0.6-1.0).  CONCLUSION: Screening rates for breast and cervical cancer among Jordanian women are inadequate. Interventions that facilitate equitable access-especially aimed at younger, less educated, rural, and low-income women-are crucial for enhancing participation and diminishing inequities in early cancer detection.

Landmark trials have shown that axillary lymph node dissection (ALND) can be safely omitted in early breast cancer patients with 1-2 positive nodes. Despite lack of prospective data, the National Comprehensive Cancer Network (NCCN) guidelines recommend that patients with 1-2 suspicious or biopsy-proven positive lymph nodes having primary surgery can undergo sentinel lymph node biopsy (SLNB). In the era of de-escalation of axillary surgery, breast cancer management in patients with clinically node-positive (cN +) axilla is driven by tumour biology and response to neoadjuvant chemotherapy (NACT). In this review, we discuss the management of the axilla in early breast cancer patients with low-volume biopsy-proven nodal disease and summarise the evidence supporting omission of ALND in these patients undergoing primary surgery.

Cancer is a multifactorial disease and the second leading cause of death worldwide after cardiovascular disease. Initially, it was considered a genetic disease or gene expression disorder, but now it is regarded as a tumor microenvironment (TME) disease. The TME consists of cancer cells, endothelial cells, fibroblasts, and immune cells that interact with each other. These interactions support tumor growth by providing nutrients via altered metabolic mechanisms such as glutamine metabolism, aerobic glycolysis, and fatty acid metabolism. The by-products of these altered metabolic pathways interfere with the function of surrounding cells and thus lead to cancer progression. The role of metabolic crosstalk highlights the intricate relationship between the cancer cells and their TME. This review comprehensively analyzes recent studies to enhance understanding of the metabolic crosstalk in TME. It highlights how tumor-associated macrophages and fibroblasts reprogram lipid and glucose metabolism to create an immunosuppressive environment. This review also provides information about the role of hypoxia-induced HIF-1α signaling in the promotion of lactate accumulation. This factor in turn ensures tumor cells' survival and makes them resistant to anti-cancer drugs. Further, we have discussed therapeutic approaches targeting TME, including use of PD-1, PD-L1 inhibitors, CAR-T cell therapy, and oncolytic viruses to improve patient outcomes. Besides this, clinical studies involving the estimation of lactate, GLUT1, and HIF-1α levels may help to recognize high-risk patients and develop guidance for personalized metabolism-targeting therapies. In the long run, such studies can ultimately improve patient outcomes and thus reduce disease burden.

Objectives: To balance the extended functional urinary voiding and morbidity outcomes amid Ileal W and Y-shaped contrasted to spherical ileocoecal (IC) orthotopic bladders subsequent prostate-sparing radical cystectomy (PRC) versus standard radical cystoprostatectomy (RC).

Material and methods: Two hundred eight male bladder cancer patients were grouped into 98 RC followed by 43-W, 31-Y, and 23-IC in comparison to 110 PRC followed by 35-W, 37-Y, and 38-IC. The functional voiding outcomes were determined by detailed patients' interview and urodynamic studies (UDS).

Results: Twenty-four hour pad-free continence for PRC at the 6th month was (37, 25, and 36%) as regards W, Y, and IC in that order, improved to (51, 44, and 51%) at the 12th month and (68, 70, 73%) at the 5th year. Nocturnal continence at the 12th month was (60, 56 and 59%). After 73 months median surveillance, day-time control was 90% equal for the 3 pouch configurations. RC patients faced inferior continence rates exclusively during nocturnal time. Urethral pressures started higher for PRC and increased over time, resulting in diminution of stress frequency. Delayed pouch morbidities were 41% for W vs. 22.4% and 25% among Y and IC series. Urethral recurrences were non-existent in both groups without atypical or metaplastic changes. Mucosal pattern persisted in 60% while muscular coat atrophied in 83% of ileal and 40% of colon walls.

Conclusion: Voiding control parameters for PRC were significantly superior. Though early continence is in favor of W pouches, delayed observation showed equivalent Y and IC results besides least delayed pouch-related morbidities for IC.

Aim: This study aimed to evaluate the multifaceted clinical utility of the RUBY phantom as a comprehensive quality assurance (QA) platform in high-precision radiotherapy, particularly for stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). The objective was to validate its performance in patient positioning, imaging system accuracy, isocenter congruency, and treatment plan verification across various complex clinical scenarios.

Materials and methods: A series of QA workflows were conducted using the RUBY phantom and its dedicated modular inserts. These included CBCT and MV/kV planar imaging for patient alignment, the Winston-Lutz insert for isocenter verification, end-to-end testing for full-chain validation, and multi-metastasis and patient-specific inserts for point dose verification. Plans were created in Eclipse TPS (v15.6) and delivered using a Varian TrueBeam STx linear accelerator with high-definition MLC. PTW Semiflex 3D and PinPoint 3D ionization chambers were used for all dosimetric verifications.

Results: CBCT- and planar image-guided alignments showed sub-millimetric deviations, with post-correction alignment verified through coincident laser and surface markers. Winston-Lutz testing across various angles demonstrated maximal deviations of ≤ 0.4 mm, which was within TG-142 recommendations. Point dose measurements for 61 SRS plans showed agreement within ± 3% of TPS calculations. End-to-end testing revealed dose discrepancies of < 1% in both coplanar and non-coplanar beam arrangements. Multi-target plans using single- and multi-isocenter approaches showed deviations of - 0.23% to - 0.50%, confirming excellent dosimetric and geometric accuracy.

Conclusion: The RUBY phantom demonstrated exceptional precision, reproducibility, and clinical adaptability across a spectrum of advanced radiotherapy QA tasks. Its integration enables the end-to-end validation of modern treatment protocols, ensuring alignment, imaging, and accuracy of dose delivery. These findings establish the RUBY phantom as a cornerstone QA solution for enhancing safety, efficacy, and reliability in high-precision radiotherapy.

Background: The potential involvement of JC polyomavirus (JCPyV) in prostate cancer (PCa) remains a subject of debate, as existing in vitro studies have produced conflicting results. Understanding the viral oncogenic mechanisms underlying prostate cancer could offer valuable insights into its etiology. This study aimed to explore the association between JCPyV infection and prostate cancer by detecting the viral large T-antigen gene in prostate tissue specimens.

Methods: A case-control study was conducted from February 2022 to March 2023, including 100 participants: 50 diagnosed with prostate cancer (cases) and 50 with benign prostatic hyperplasia (BPH) as controls. Formalin-fixed paraffin-embedded (FFPE) prostate tissue samples were collected from all participants. Nested polymerase chain reaction (PCR) was employed to detect JCPyV large T-antigen DNA using specific primers. Demographic and clinical data were obtained via a structured questionnaire. Statistical analysis was carried out using SPSS version 20, and associations between JCPyV presence and prostate cancer were analyzed using logistic regression.

Results: The mean age of the prostate cancer group was 67.5 ± 10.9 years, compared to 70.9 ± 8.9 years in the control group. JCPyV large T-antigen DNA was detected in 29 out of 50 (58%) prostate cancer cases, compared to 19 out of 50 (38%) controls (P = 0.045; odds ratio = 1.45; 95% confidence interval: 1.011 to 5.019). Within the prostate cancer group, patients testing positive for the JCPyV T-antigen had a mean age of 73.3 ± 8.7 years, significantly higher than T-antigen-negative patients, whose mean age was 67.0 ± 8.3 years (P = 0.029).

Conclusion: The prevalence of JCPyV large T-antigen gene was significantly higher in prostate cancer patients than in individuals with benign prostatic hyperplasia. These findings suggest that JCPyV infection may be linked to an increased risk of prostate cancer, reinforcing prior studies that imply a potential oncogenic role for the virus in prostate carcinogenesis. Further investigations are necessary to elucidate the molecular mechanisms driving this association and its potential clinical implications.

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. The limitations of conventional therapies, namely severe side effects and the emergence of drug resistance, underscore the urgent need for novel and more effective treatment strategies. Natural products, including bioactive compounds derived from scorpion venom (SV), have demonstrated promising anticancer properties in various studies. This study aimed to investigate the potential chemopreventive and therapeutic effects of Leiurus quinquestriatus venom (LQV) and Androctonus bicolor venom (ABV) against chemically induced CRC in a rat model. Male rats were randomly assigned to four groups: Group 1 (Gp1) (control), Gp2 (CRC induced using 40 mg/kg 1,2-dimethylhydrazine (DMH), administered subcutaneously for 4 weeks), and Gp3 and 4 (DMH-induced CRC treated intraperitoneally with 0.025 mg/kg LQV and 0.05 mg/kg ABV, respectively, for 11 weeks). At the end of the experimental period, colon tissues were collected for histopathological examination, tumor biomarker analysis, gene expression profiling, cell cycle distribution, and apoptotic assays. Both LQV and ABV significantly reduced the number of aberrant crypt foci (ACF) and mucin-depleted foci (MDF) while enhancing the number of goblet cells in colonic mucosa. Treatment also resulted in a marked downregulation of proliferating cell nuclear antigen (PCNA) and cyclin D1 and upregulation of the tumor suppressor gene PTEN. Moreover, flow cytometry analysis revealed an increase in late apoptotic cells and cell cycle arrest at sub-G1 and G0 phases in venom-treated groups. These findings suggest that LQV and ABV possess notable anti-CRC activity through modulation of proliferation, apoptosis, and gene regulation, highlighting their potential as candidates for alternative CRC therapies.

Background: Tislelizumab, a PD-1-targeting monoclonal antibody, can potentially treat advanced esophageal squamous cell carcinoma (ESCC). Using pooled clinical data, this study evaluates Tislelizumab's efficacy and safety in advanced ESCC.

Methods: This review followed PRISMA guidelines, with a comprehensive search conducted across PubMed, ProQuest, EBSCOhost, and Google Scholar for clinical trials involving ESCC patients treated with Tislelizumab. Primary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). We evaluated the study quality using the Cochrane Risk of Bias and ROBINS-I tools. Data extraction and pooling were performed using R for single-arm studies and RevMan 5.4 for RCTs. Outcomes were analyzed using pooled medians, hazard ratios for OS and PFS, and relative risks for ORR, DCR, and adverse events.

Results: Four studies with 1,202 patients met inclusion criteria. The risk of bias was low to moderate. Pooled data indicate a median OS of 8.6 months and PFS of 4.75 months in the Tislelizumab group, with an overall ORR of 0.40 (95% CI: 0.20-0.61) and DCR of 0.64 (95% CI: 0.36-0.88). Tislelizumab significantly improved OS (HR 0.68, 95% CI: 0.59-0.78, p < 0.0001), PFS (HR 0.71, 95% CI: 0.54-0.93, p = 0.01), ORR (RR 1.65, 95% CI: 1.22-2.24, p = 0.001), and DCR (RR 1.11, 95% CI: 1.04-1.18, p = 0.001) compared to standard chemotherapy. Pooled rates of grade 3 or more AEs and serious AEs were 0.56 (95% CI: 0.17-0.92) and 0.28 (95% CI: 0.10-0.50), respectively. There were no significant differences in grade 3 and serious AEs between Tislelizumab and standard chemotherapy. The most common AEs reported included hematologic toxicities, gastrointestinal issues, metabolic disturbances, and biochemical abnormalities.

Conclusion: Tislelizumab improves survival and response in advanced ESCC patients, particularly when combined with chemotherapy, with an acceptable safety profile. These findings support its continued use in ESCC, though further investigation is warranted due to the limited number of studies.

Trial registration: CRD42024564367.