Middle East Journal of Cancer
Volume:11 Issue: 2, Apr 2020

Acute myeloid leukemia (AML) is a complex disease that is linked to genetic and environmental factors. The gluthatione S-transferase (GST) is a family of enzymes that play a crucial role in the detoxification of carcinogens. These compounds could cause DNA damage, which might lead to the development of cancer. Interindividual inherited differences caused by the presence of single nucleotide polymorphisms (SNPs) in detoxification enzyme, could play a major role in cancer predisposition. The present study aimed to investigate the association between GST gene polymorphisms and AML risk.
The GSTP1 genotype was determined by the PCR-RFLP and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was conducted to evaluate the association between GST gene and the risk of AML.
We found that GSTT1 null genotype was significantly associated with the risk of AML. However, GSTM1 and GSTP1 polymorphisms did not influence the AML risk. Subjects carrying the GSTM1 Present, GSTT1 null and GSTP1 Ile / Val et Val /Val genotypes had a higher risk of developing AML. The results of meta-analysis showed a positive association between GSTM1 null, GSTT1 null and Ile105Val GSTP1 polymorphisms and AML risk in East Asians, Caucasians, and mixed populations, respectively.
GST gene polymorphisms may be risk factors for acute myeloid leukemia.

The apoptotic route is mostly damaged in gastric cancer tumor cells. DNA methylation of promoter associated CpG islands inactivates tumor suppressor genes. The objective of the present study was to analyze the hypermethylation of death-associated protein kinase (DAPK) and Bcl-2-associated X protein (BAX) genes in individuals suffering from gastric cancer and undergoing chemotherapy.
Genomic DNA was extracted from blood samples and the tissue fixed in the paraffin of 30 patients and normal individuals. Hypermethylation investigation of DAPK and BAX genes was conducted via methylation specific PCR technique, the outcomes of which were analyzed through electrophoresis and SPSS software version 20.
Methylation of both BAX and DAPK genes with a frequency of (28.3%, 21.7%) in blood and (23.3%, 23.3%) in tissue, respectively, had a significant relationship with gastric cancer (P˂0.01). A significant relationship was also observed between the methylation of BAX gene in tissue and tumor type (12, 35.3% and P˂0.01). No relationship was found between methylation and grade, stage, node, age, sex, and other pathologic and clinical data of the patients (P>0.05). There was a significant association between simultaneous methylation of DAPK and BAX genes in tumor and typical tissues with methylation a frequency of 40% and 95.83%, respectively (P˂ 0.01).
Methylation of the BAX and DAPK genes can be used as a biomarker in bloodand an approach in the early detection of malignity and illness management. Methylation inhibitors with the potential for drug targeting of DAPK and BAX can further be employed in pharmacotherapy.

Activation of IKK/NF-kB signaling pathway plays a critical role in inflammation-driven tumor progression. Several natural compounds able to inhibit the IKK/NF-kB activation pathway have been shown to either prevent cancer or inhibit cell growth. Extensive studies have been carried out on the Nigella sativa (N. sativa) by many researchers, and its pharmacological activities including anticancer, analgesic, and anti-inflammatory functions have been explored. This study investigated the effect of N. sativa extract on the mRNA level of NFk (p50, RelB) and IKK (IKKA, IKKB) to determine one of the anti-inflammatory mechanisms of N. sativa in breast cancer cells.
In this experimental study, MCF7 cell line was treated with different concentrations of hydroalcoholic extracts of N. sativa (0, 200, 400,600,800 μg/mL) for 24, 48 and 72 h. Effects of the extract on cell viability and NFk (p50, RelB ) and IKK (IKKA, IKKB) gene expression were analyzed by MTT assay and real time PCR, respectively.
mRNA expression levels of NFk (p50, RelB) and IKK (IKKA, IKKB) in the treatment group were lower than the untreated (control) group. Fold difference (p50, RelB) of gene expressions in treatment groups were statistically significant (P =0.001 and P =0.003) and the fold difference of IKK (IKKA, IKKB) in the treatment groups was lower than that of the untreated groups (P=0.01 and P=0.001).
One possible anti-inflammatory mechanism of N. sativa is associated with the reduction in mRNA levels of NFk (p50, RelB) and IKK (IKKA, IKKB) in breast cancer.

Dacarbazine is considered as a standard treatment for melanoma, but resistance to anticancer therapy is a major cause of cancer stem cells invasion. In vitro assays have shown that metformin interferes with cell viability, proliferation, and apoptosis.
Melanoma cell line B16f10 was treated with dacarbazine IC50, metformin in different doses (0.5, 2 and 8 mM) and combination therapy. The influence of treating and cell viability was determined with MTT assay, and the effect of treat on colonization was quantified. Changes in cleaved PARP were investigated using immunoblotting. The cytotoxicity effect of Dacarbazine was further analyzed.
Metformin induced cytotoxicity on B16-F10 cells; cell viability, determined at various time intervals (24 and 48 h) and in the presence of different drug concentrations (≅0.7μM), was reduced by ~50% following 24 h. The proliferation rate was evaluated over 24-48 hours and 12 days using varying subcytotoxic and cytotoxic concentrations of metformin (2-8μM), which was reduced in a dose-dependent manner. Resistance cells resulted in slender spindles and better colonization. Finally, metformin decreased the cytotoxicity of dacarbazine and increased apoptosis.
A study with B16-F10 cells showed that the drug combination induces significantly more apoptosis compared with when each drug is individually used. B16F10 was the most sensitive and resistant at a normal dose of metformin and dacarbazine, which is a very encouraging result with regards to the possibility of metformin becoming a new tool for melanoma research and treatment.

Acute lymphoblastic leukemia (ALL) is a heterogeneous group of lymphoid neoplasms resulting from the proliferation of malignant lymphoid cells. The aim of this study was to evaluate treatment-related complications in children with ALL receiving the Medical Research Council (MRC) UKALL X protocol.
In this retrospective cross-sectional study, children with ALL receiving the MRC UKALL X protocol from 2008 to 2015 in Bahrami University Hospital, Iran, were enrolled. The clinical and morphological features were analysed and treatment-related complications were assessed.
Out of 67 children with ALL receiving the MRC UKALL X protocol, 44 (65.6 %) were boys and 23 (34.4%) were girls. Seven patients (10.7%) relapsed in the three years of diagnosis, and 50 children (74.6%) had an overall survival of three years. Average age in three-year-survival group and mortality group was 6.92 (SD: 3.96) and 6.35 (SD: 7.47), respectively (P= 0.38).
Overall survival and relapse rates in this study confirm that this protocol is an appropriate treatment strategy.

Cisplatin (CP) is a potent antineoplastic agent in the treatment of wide a range of cancers, but it is accompanied with nephrotoxicity, a major limiting side effect. The aim of the present study was to evaluate the possible protective effect of vitamin E in the prevention of CP-induced nephrotoxicity.
In this randomized clinical trial, a total of 51 patients treated with CP chemotherapy were randomly assigned to receive vitamin E supplementation (400 Iu/ daily) (N=26) or placebo (N=25). Serum creatinine, glomerular filtration rate (GFR), and neutrophil gelatinase-associated lipocalin were measured prior to each chemotherapy cycle and one month after the cessation of the cycles.
Compared to the baseline, a significant decrease was observed in the blood levels of neutrophil gelatinase-associated lipocalin and serum creatinine in the vitamin E group (P=0.001). GFR was not reduced in the vitamin E group (P=0.001), and vitamin E was generally tolerated well.
Our findings indicated that vitamin E exert protective effects against CP-induced nephrotoxicity, a finding which requires larger studies for confirmation.

The relationship between HPV infection and skin squamous cell carcinoma (SCC) development in immunocompetent individuals is unclear. Therefore, the purpose of this study was to assess the association between HPV infection and skin SCC.
HPV DNA prevalence was evaluated in the paraffin embedded specimens of 70 immunocompetent patients, of which 35 patients had skin SCC and 35 had normal skin. PCR technique and GP6/5 primers were utilized for HPV DNA detection.
Based on this study, 14.3% of the cases (5 of 35, 2 with low risk and 3 with high risk viruses) and 2.9% of the controls (1 of 35 with low risk virus) had papilloma viruses. However, there was no significant statistical relationship between the HPV DNA presence and the SCC development in skin.
The direct effect of HPV on skin cancerogenesis remains questionable.

Oral cavity, as the main source of complications such as infection, is unfortunately ignored in cancer patients. In this study, the frequency, type, and location of oral mucosal lesions were determined among patients admitted in the hematology and oncology department.
In this cross-sectional study, 88 admitted patients were examined between November 20, 2017 to August 21, 2018. Demographic data, history of smoking, and denture use were documented. Oral examinations were further conducted to evaluate oral soft tissue lesions according to the checklist.
88 hospitalized patients were screened, out of whom 57(64.7%) had at least one lesion. A total of 79 oral mucosal lesions were identified and ulcerative lesions, found in 51 (57.9%) patients, were among the most frequently encountered problems. Pigmented lesions were more prevalent in smokers (P<0.001). Red and white lesions were significantly more than other lesions among complete denture wearing patients.
In light of the high prevalence of oral complications in our patients, this study indicates the need for consultation with oral medicine specialist for a timely diagnosis and better management during the treatment process.

Bladder cancer is the second most common urinary cancer after prostate cancer. Recent studies have shown higher serum and urinary vascular endothelial growth factor (VEGF) in increased angiogenesis. In this study, the mean serum and urine level of VEGF was assessed in patients with bladder cancer. In this case-control study, 46 patients with bladder cancer referred to Imam-Khomeini Hospital in Tehran, Iran and 38 subjects as control, were enrolled and the mean serum and urine level of VEGF was assessed and compared between the groups. The mean serum level of VEGF was 478.7, 518.4, and 648.1 in control, low-grade, and high-grade groups, respectively, with no significant difference (P=0.175). The mean urine level of VEGF was 414.2, 968.3, and 848.4 in control, low-grade, and high-grade groups, respectively, with significant difference (P=0.010). The mean urine level of VEGF in patients with bladder cancer is higher than healthy subjects.

Antineoplastic drugs are among medications that have narrow therapeutic index and high toxicity. For this reason, medication errors in patients with cancer are important and there have been myriads of efforts to decrease them. In this study, we attempted to assess the medication errors by designing chemotherapy standard forms for patients with Hodgkin’s and non-Hodgkin’s lymphomas.
This cross-sectional study was performed in Omid and Imam Reza Hospitals, Mashhad, Iran from January 2016 to October 2016.The forms have been designed by clinical pharmacist based on available international guidelines and validated by clinical oncologists working in these two centers. Therapeutic regimens were selected by clinical oncologists and adherence of the oncologists and nurses to this form and probable medication errors were identified by the pharmacy students.
In 206 visits of 62 Hodgkin’s and non-Hodgkin’s lymphoma patients, overall 790 antineoplastic drugs were administered to patients in whom 160 drugs were associated with medication error. The most common errors included improper dose (65%) and wrong infusion time (35%). One of the most important reasons for dosing errors was miscalculation of the BSA (40%).
This study shows that about two third of errors were improper dose. It seems that chemotherapy standard forms, if properly followed by nurses and physicians, could be useful and effective to reduce medication errors.

Breast cancer is the most common cancer among women. Considering its long process of the treatment and significant influence on the health of patients, we aimed to investigate the functional and symptom scales of quality of life and the factors affecting patients with breast cancer during chemotherapy.
In this cross-sectional study, 94 women with breast cancer visiting Imam Reza Healthcare Center in Mashhad, who were in the course of chemotherapy, selected through convenience sampling. To investigate the functional and symptom scales of the quality of life, EORTC QLQ-BR23 was used. Data was analyzed via multiple linear regression model and significance level was considered as 0.05.
In functional scales, the highest and lowest score were obtained for sexual functioning (38.12±18.55) and future perspective (17.73±19.98), respectively. In the symptom scales, the highest and lowest score belonged to upset by hair loss (28.39±25.66) and breast symptoms (6.74±10.39), respectively. The results of multiple regression analysis showed that education had a negative effect on body image, menopause had a positive effect on sexual function, and tumor size had a negative effect on breast symptoms.
Breast cancer deserves serious consideration as it affects different aspects of quality of life. Therefore, it is absolutely essential to take some measures for early diagnosis, achieve better therapeutic methods, use supportive therapy to decline the symptoms of the disease, and promote the functional level of women with breast cancer.

Strong fear of cancer recurrence is frequently reported among the cancer survivors. Such influential and universal fear is one of the factors that cause considerable emotional distress, anxiety, and decreasing quality of life among such patients. Given the importance of the subject, it is necessary to select psychological interventions in which the efficiency and feasibility have been proved in different trials. The present study aims to determine the efficacy of mindfulness-based stress reduction on fear of cancer recurrence in patients with colorectal and breast cancer.
The current study is a randomized clinical trial with experiment and control groups. We selected 38 patients with breast and colorectal cancer who referred to Shahid Motahari Clinic and Amir Oncology Hospital in Shiraz (96-97), then randomly assigned them to intervention and control groups. They filled out questionnaires in the pre-test and post-test. The data were analyzed by multivariate statistical test with SPSS v. 23 software.
Findings show that the post-test mean scores in the fear of cancer inventory have decreased in the intervention group and there was a significant difference between experimental and control groups in the components of fear of cancer inventory as follows: triggers (F=55.289, P<0.0001), severity (F= 75.785, P<0.0001), psychological distress (F=24.078, P<0.0001), dysfunction (F=62/025, P<0.0001), coping strategies (F=15.592, P<0.0001), reassurance (F= 6.235, P<0.017), and except insight (F= 1.396, P<0.245).
The results from this study showed that MBSR is an efficacious intervention to reduce fear of cancer recurrence in patients with breast and colorectal cancer.

ARID1A, a bona fide tumor suppressor, is the third most mutated gene in human colorectal cancer. In this paper, we reported the identification of a novel mutation in one of 20 primary human colorectal cancer tumors. Sanger sequencing of the exon 3 of the ARID1A gene revealed a novel heterozygous non-sense mutation of the c.1653C>G. This resulted in the premature termination of the 2285 amino acid protein at the 551st codon. Mutation Taster predicted this novel mutation to be pathogenic. Immunohistochemical analysis revealed the loss of ARID1A protein expression in cancerous tissues harboring ARID1A mutation. As far as we know, this is the first report on the mutation of ARID1A gene in an Iranian patient. This mutation can expand the spectrum of ARID1A gene pathogenic mutations among colorectal cancer patients.

Neuroblastoma is an extracranial solid tumor that is most commonly observed in children, yet it is rare to have brain metastasis in neuroblastoma during primary involvement or relapse. In this article, we report a successful treatment of high risk neuroblastoma with primary leptomeningeal metastasis based on developing countries facilities and explain combination chemotherapy (a classic regimen with salvage regimen based on temozolamid and methotroxate intratechal chemotherapy and localized radiation therapy) as a multimodal therapy.

The prevalence of suicide is high in patients with prostate cancer. The hypothalamic– pituitary–adrenal (HPA) axis disorder plays a role in the pathophysiology of depression and suicidal ideation. Acupuncture regulates cortisol secretion through controlling the activity of HPA axis. The purpose of this study was to evaluate the effectiveness of acupuncture on decreasing depression, suicidal ideation, and cortisol secretion in a patient with prostate cancer. In a single-case experimental study, lasting from December 2015 to June 2016, a patient suffering from prostate carcinoma with dysthymic disorder and suicidal ideation was selected through purposive sampling method. Following 30 days of evaluation at baseline, the subject was treated for four weeks with auricular acupuncture along with the usual treatment. The results were analyzed by generalized estimation equation (GEE) and Repeated Measures Correlation (rmcorr) through statistical package for the social sciences (SPSS) software version 22. The primary outcomes showed that acupuncture had a significant effect on reducing depression index, suicidal ideation, and cortisol levels during the treatment process (all P values< 0.05). Secondary outcomes further showed that a significant positive correlation existed between depression, suicidal ideation, and salivary cortisol levels (all P values < 0.05). The findings of this study showed that auricular acupuncture can replace medication and psychotherapy to reduce depression and suicidal ideation and regulate HPA-axis function through modulating the cortisol secretion. However, this conclusion requires more high-quality randomized clinical trials.