Journal of the Egyptian National Cancer Institute最新文献

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.

Gliomas represent predominant and fatal central nervous system (CNS) cancers lacking a gold standard of treatment, which need accurate prognosis, diagnosis, and intervention. Glioma accurate therapy using common traditional approaches such as surgical treatment, radiotherapy, and chemotherapy results insufficient mainly due to side effects, recurrence, and resistance. Scientific and medical challenges can be decreased considering novel therapeutic targets. The multiple and diverse role of microRNAs (miRNAs) in cellular processes has been demonstrated. The appreciation of miRNAs regulatory roles in cancer cell proliferation or growth inhibition opens new perspectives in the development of novel strategies targeting cancers. Six inducers (miRNAs) including miR-363-3P, miR720, miR-484, miR-890, miR-496, and miR-939-5p can develop into glioma cells with the potential of therapeutic targets. Therefore, the tracking of glioma stage and response to anticancer therapy is associated with various miRNAs. The objective of this review is to provide a comprehensive assessment of the role of miRNAs in glioma cancer development.

Background: Solid pseudopapillary tumor (SPT) is a rare tumor of the pancreas with a low degree of malignancy. This tumor is most common in the female field, and in the children's population, this pathology is less common and occurs on average for the ages of 11-14 years old. The differential diagnosis of the tumor is difficult due to the lack of specific symptoms. The most informative methods of examination are computed tomography (CT) and magnetic resonance imaging (MRI). Surgical treatment is currently the most beneficial method of choice for the treatment of SPT.

Case presentation: A 9-year-old girl for the first time experienced multiple episodes of vomiting and abdominal pain against the background of complete well-being. There were performed ultrasound examination, CT, and MRI, the results of which revealed a cystic neoplasm of the head of the pancreas. There was carried out a differential diagnosis with serous cystadenoma, mucosal cystadenoma, and SPT. The child underwent surgical intervention - upper-median laparotomic access and enucleation of the tumor of the hook-shaped process of the pancreas. The postoperative period proceeded smoothly. According to the histological examination, there was identified the solid-pseudopapillary tumor of the pancreas.

Conclusion: The presented clinical case of tumor enucleation of a rare uncinate process tumor in a child is an alternative to radical surgical resections of the pancreas.

Background: Aromatase inhibitors have demonstrated superior outcomes compared to tamoxifen in various studies. However, research in Africa, including Kenya, where breast cancer mortality rates are disproportionately high, is lacking.

Objectives: The study aimed to assess the comparative efficacy of tamoxifen and aromatase inhibitors among hormone receptor-positive breast cancer patients at Kenyatta National Hospital.

Methods: A retrospective cohort study was conducted at the Oncology Department of Kenyatta National Hospital, involving all eligible hormone receptor-positive breast cancer patients treated in the facility between 1st January 2019 to 31st December 2022. The study was hospital-based and used a data abstraction tool to collect data from the patients' medical records. The data obtained was then analyzed using SPSS version 25 and Kaplan-Meier analysis was used to estimate the median survival time. Cox regression analysis was employed to determine whether there was a significant association between the variables. The collected data was presented in the form of frequency tables and graphs.

Results: In our study, aromatase inhibitors consistently demonstrated superior outcomes compared to tamoxifen across various parameters. Specifically, aromatase inhibitors showed a lower incidence of disease progression (24% vs. 29.7%), a higher rate of complete radiological response (24% vs. 13.5%), and a reduced likelihood of developing distant metastasis while on treatment, coupled with a lower mortality rate (40% vs. 48.0%). Additionally, the median survival time for patients receiving aromatase inhibitors was notably longer at 49.0 months compared to 42.0 ± 3.6 months for those on tamoxifen (P = 0.410). Similarly, the aromatase inhibitor group exhibited a more extended median metastasis-free survival time (42.0 months vs. 30.0 ± 1.4 months, P = 0.056) and a more favorable survival time from metastasis to death (8 ± 0.6 months vs. 6 ± 0.8 months in the tamoxifen group, P = 0.142).

Conclusion: These findings collectively suggest a consistent trend towards improved treatment outcomes with aromatase inhibitors compared to tamoxifen. The observed reduction in mortality rates among aromatase inhibitor-treated patients highlights their potential clinical benefit, with superior overall survival and disease progression.

Background: Adequate nutrition can mitigate side-effects and improve recovery for patients with locally advanced head-and-neck squamous cell cancer (LAHNSCC), while malnourishment can increase morbidity and mortality. We aimed to evaluate the baseline nutritional status of patients with LAHNSCC planned for curative chemoradiotherapy (CRT), the evolution of nutritional status during the course of CRT and to assess whether nutrition impacted their clinical outcomes.

Methods: This was a pre-planned secondary analysis of a Phase III randomized controlled trial conducted between 2013 and 2017 in 300 patients with LAHNSCC who were randomly assigned to receive either cisplatin 30 mg/m² once-a-week or 100 mg/m² once-in-3-weeks concurrently with radiation. This analysis included 112 patients for whom nutritional parameters were recorded. Patient Generated Subjective Global Assessment (PG-SGA) forms were used to evaluate malnutrition severity at different treatment stages. Scores on the PG-SGA ranged from 0 to 35, with higher scores denoting greater malnutrition. Scores were grouped, with 0-3 indicating normal to mild malnutrition, and ≥ 4 denoting moderate to severe malnutrition. Baseline scores were compared with subsequent scores and survival outcomes were analyzed.

Results: At baseline assessment, 42.8% of patients had normal to mild malnutrition, while 57.1% had moderate to severe malnutrition. There were higher baseline malnutrition rates in women, users of smokeless tobacco, and patients with buccal mucosa tumors. By day 21 of treatment, 44 (56.4%) patients had moderate to severe malnutrition, while 34 (43.6%) had normal nutrition or mild malnutrition. Among those with moderate to severe malnutrition at baseline, 13 (29.5%) patients had an improvement in their nutritional status, while 14 (41.2%) patients with normal to mild nutrition at baseline had deterioration in their nutritional status during the course of CRT. Baseline nutritional status did not significantly impact progression-free, locoregional relapse-free or overall survivals.

Conclusions: Pre-treatment nutrition is crucial for managing weight and reducing treatment complications in patients with LAHNSCC. Over 40% of patients with normal baseline nutrition have deterioration of their nutritional status during CRT. We were unable to find any correlation between nutrition and clinical outcomes in patients with LAHNSCC receiving curative CRT. Larger studies are needed to explore the impact of nutrition on treatment outcomes, emphasizing regular dietary assessments and interventions to improve patient compliance.

Trial registration: Clinical Trial Registry of India, under the registration number CTRI/2012/10/003062.