The drug 6-thioguanine (6-TG) is one of the thiopurines successfully used in oncology, especially for acute myeloid leukemia (AML). It is proposed to act as an epigenetic drug affecting DNA methylation. The aim of this study was to clarify the effect of 6-TG on the proliferation, viability and expression of genes coding for the enzymes DNA methyltransferase 3A and DNA methyltransferase 3B (DNMTs) as well as histone deacetylase 3 (HDAC3) and histone deacetylase 7 (HDAC7) in the human promyelocytic AML cell line HL60.
In this experimental study, HL60 cells and also normal peripheral blood mononuclear cells (PBMCs) were grown in RPMI 1640 medium containing 10% fetal bovine serum. They were then treated with 6-TG at their exponential growth phase. Cell viability was monitored using the Cell Counting Kit-8 assay with an enzyme-linked immunosorbent assay (ELISA) reader. The expressions of the above mentioned 4 genes were quantified using real-time PCR.
6-TG could inhibit the proliferation of HL60 cells and decrease their viability. In HL60 cells, as compared to normal PBMCs, 6-TG significantly decreased HDAC3 (p = 0.0034) as well as DNMT3B (p = 0.03) and HDAC7 (p = 0.0031) gene expressions, but increased the expression of DNMT3A gene (p = 0.16) after normalization to GAPDH as the housekeeping gene.
These findings suggest that the altered expression of DNMT3A, DNMT3B, HDAC3 and HDAC7 genes is responsible for at least part of the antitumor properties of 6-TG, providing an insight into the mechanism of its action as an epigenetic drug.
Background: Kidney function test (KFT) is a routine laboratory examination used in the diagnosis of many disorders, the kidney participates in several essential functions in the human body, and kidney dysfunction can lead to morbidity and mortality. Therefore, studying the levels of KFT in early diagnosed cancer patients can identify how the kidney perform when cancer begins, and which parameter of KFT is affected early.
Objective: This study aimed to evaluate levels of kidneys function profile including blood urea, creatinine, sodium (Na), potassium (K), and chloride in untreated cancer patients.
Patients and methods: 211 participants including 44 healthy controls and 167 patients diagnosed as early cancer were enrolled in this study in Taif city, and this study was performed at King Faisal Hospital (KFH) and Taif University. Serum levels of blood urea, creatinine, sodium (Na), potassium (K), and chloride were analyzed. The total number of patients was 167 and healthy controls were 44. Types of cancer in the patients included in this study were 49 breast cancer, 45 gastrointestinal tract cancer, 39 gynecological tumors, 17 head and neck cancer and 17 respiratory cancer. Statistical assessment was done by applying T-test, Chi-square, odds ratio.
Results: Sodium, potassium, creatinine and chloride levels were significantly higher in cancer patients compared to the healthy controls and the urea was normal and nothing was significant.
Conclusion: Most common electrolytes abnormality increased in our study group of cancer patients. A sudden death could be resulted when the potassium level increased rapidly. Dysregulation in urea, chloride and creatinine could be a cancer marker and lead to fatal problems.
Сysts of the neck are congenital cystic lesions of the neck, often presenting in childhood. Complete surgical excision is the treatment of choice for these lesions. Recurrence of cystic lesions of the neck after incomplete excision is fraught with complications due to the need for a second surgery and complications of the recurrent cyst itself. We herein report the details of recurrent cysts of the neck presenting at 3, 6, 12 and 18 months postoperatively.
Introduction: Whether human leukocyte antigens (HLAs) and human endogenous retroviruses (HERVs) affect therapeutic outcomes is unknown. Here, we focused on the similarity between HERV and human immunodeficiency virus (HIV) genes.
Methods: By comparing training and validation sets in pooled 2,049 gastric cancers, we evaluated the significance of baseline HLA examination in clinical treatment response. HLA-restricted CD8+ cytotoxic T-lymphocyte (CTL) epitopes on HERV and HIV genes were predicted using bioinformatics. HLA-restricted putative HERV peptides were selected based on the similarity of HLA-restricted HIV peptides. Changes in CD8+ cells were compared at baseline and 1 year after gastrectomy.
Results: We identified 53 fully recovering subjects who received effective therapies in the validation set, based on the HLA of 101 patients who received effective therapies in the training set. We found putative 84 HERV-derived peptides that might have induced HLA-restricted CTL by administering therapies in 2041 subjects. We identified 155 subjects, whose CD8+ cells increased significantly after administering therapies in only females (paired t-tests, P = .005), resulting in significantly better survival compared with CTL (-) patients (hazard ratio [HR], 5.05; 95% CI, 3.42 to 8.92; P < .0001 [female: HR, 8.46; 95% CI, 3.15 to 22.72; P < .0001, male: HR, 3.89; 95% CI, 2.20 to 6.88; P < .0001]). All CTL (+) females received effective therapy and CTL (+) unclassified patients survived during the follow-up period.
Conclusions: We confirmed the clinical significance of HLA. Research on HLA-restricted HERV gene-derived peptides may reveal the central mechanism of sex bias in therapeutic responses.
Inflammatory breast cancer (IBC) is a rare but aggressive type of breast carcinoma. There are few diagnostic and prognostic biomarkers in IBC. Aldehyde dehydrogenase 1 (ALDH1) is a putative stem cell marker in a variety of cancers. Our study aims to investigate the expressions of the ALDH1 in a cohort of IBC tumors and to assess the relationship of their expression with Notch1 and some clinic-pathological characteristics.
Methods: We investigated the status of ALDH1 and Notch1 in 81 female IBC cases. Paraffin-embedded tumor tissues (FFPE: formalin-fixed paraffin embedded) were obtained from all cases and to mRNA was extracted from FFPE tissue. Pure RNA was used for the synthesis of cDNA, which was used for quantitative real-time RT-PCR (qRT-PCR) analysis of relative expression levels of target genes.
Results: Positive ALDH1 (ALDH1+) and Notch1 (Notch1+) expression was observed in 69 (85%) of 81 IBC cases. Of the ALDH1+ tumours, 29 (34.9%) were of the luminal subtype, 21 (25.3%) were in the HER2 subtype and one (1.5%) was in the unclassified category. In addition, 32 (38.2%) were triple-negative tumours. The majority 50 (60.2%) of ALDH1+ cases were high-grade ductal carcinomas. ALDH1 expression is significantly correlated with age, response treatment and Notch1 expression (p < 0.05). Interestingly, statistic analysis using Khi2 test shows that the positively ALDH1 and Notch1 have an interactive effect IBC cases (p < 0.05).
Conclusion: This finding reflects that the assessment of ALDH1 expression may have a potential role in incidence of IBC and be helpful tool in the future anticancer strategies.
Objective: In Morocco, 3 246 new cases of upper aerodigestive tract cancer (UADTC) were diagnosed in 2020. The main risk factors are tobacco and alcohol; other risk factors have been identified or suspected. This study aimed to investigate potential risk factors associated with the UADTC sites.
Methods: A cross-sectional study has been conducted from December 2018 to February 2020 at the National Institute of Oncology in Rabat. Data were collected using a face-to-face structured and pre-tested questionnaire among patients with UADTC. Medical records were abstracted to complete clinical information. The use of a Chi-Square test with a value of a 95% confidence level helped to predict the association between potential factors and UADTC.
Results: 201 patients agreed to take part in the study, with an average age of 54.1 years; 48.3% of the participants were illiterate; 74.1% were poor, and 52.7% were diagnosed at stage IV. The Pearson Chi-Square test showed a significant relationship between smoking and cancers of the oral cavity (p = 0.039), nasopharynx (p < 0.001), and larynx (p < 0.001). Alcohol was also associated with cancers of the oral cavity (p = 0.049), nasopharynx (p < 0.001), oropharynx (p = 0.047), and larynx (p < 0.001). In addition, a significant relationship was also demonstrated for both tobacco and alcohol users and cancers of the oral cavity (p = 0.041), nasopharynx (p < 0.001), oropharynx (p = 0.042), and larynx (p < 0.001). Oral hygiene (p = 0.049), and prosthetic irritation (p < 0.001) were associated with oral cavity cancers only.
Conclusion: In the present study, the identified at-risk individuals could be admitted for clinical examination and for focused preventive treatment measures.
Cancer is the leading cause of death worldwide. Despite significant advances in cancer treatment, morbidity and mortality rates remain high. Tumor heterogeneity, particularly intertumoral heterogeneity, is a major cause of cancer therapy failure, underpinning tumor treatment problems and a variety of available therapeutic strategies, including molecularly targeted therapies. Recent advances in massively parallel sequencing and digital genomic techniques suggest that cell-free circulating tumor DNA (ctDNA) can be used as a “liquid biopsy.” In the case of breast cancer, ctDNA found in plasma can be used to non-invasively scan tumor genomes and assess tumor burden.
ctDNA in plasma can be used to identify important genetic anomalies, track treatment responses, uncover drug resistance, and detect disease progression before clinical and radiographic confirmation. Furthermore, ctDNA can be used to identify tumor heterogeneity and metastasis-specific mutations, providing information to aid in patient treatment.
We focused on the current state of cell-free ctDNA, including ctDNA biology, recently developed ctDNA detection techniques, and breast cancer-specific detection methods, with a focus on clinical applications of ctDNA-based biomarkers in breast oncology.
Introduction: It is unclear whether the early removal of urinary catheters during epidural analgesia increases postoperative urinary retention. This systematic review and meta-analysis aimed to evaluate the risk of postoperative urinary retention by comparing early removal with late removal of urinary catheters after surgery with epidural analgesia.
Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, World Health Organization International Clinical Trials Registry Platform, and Clinical Trials.gov for randomized controlled trials involving early versus late removal of urinary catheters after surgery with epidural analgesia. Primary outcomes were postoperative urinary retention and urinary tract infection, and we conducted a meta-analysis using a random-effects model to calculate the pooled estimates of risk differences. The Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development, and Evaluation approach were used to assess the quality of individual studies and the overall body of evidence, respectively.
Results: Four studies involving 584 patients were included. The pooled risk difference of early versus late removal was 0.05 (95% confidence interval, -0.01–0.10; I2 = 59%) for postoperative urinary retention and -0.03 (95% confidence interval, -0.12–0.05; I2 = 89%) for urinary tract infection. We did not conduct a meta-analysis regarding length of stay.
Conclusions: Early urinary catheter removal may be associated with a 5% increased risk of postoperative urinary retention. We could not conclude whether this increased risk of postoperative urinary retention is clinically acceptable or not.