Middle East Journal of Cancer
Volume:9 Issue: 2, Apr 2018

Anthracycline therapy for acute leukemia may be associated with significant morbidity and mortality in children or elderly patients that have a degree of heart failure. Patients with prior anthracycline exposure, those with pre-existing heart disease, or who have received the total anthracycline dose present an increased risk for cardiotoxicity. Therefore, new chemotherapy regimens in these situations would be life saving for leukemia patients. We have conducted a systematic review of possible strategies for rescue regimens without anthracycline in refractory acute leukemia patients.
We gathered the data from 5 creation databases and relevant website until August 2016. We selected randomized clinical trials or other studies that used anthracycline-free chemotherapy regimens to treat acute refractory leukemia in children and adults. The quality of the studies was evaluated according to the Cochrane risk of the polarization tool. All stages of the review were independently conducted by two authors. We obtained data from 75 main clinical trials.
There were 75 trials included from which 4 were considered to be at low risk for bias. Most trials showed that the improvement did not reach statistical significance.
Evidence existed to support the use of the combination of fludarabine, cytarabine, and filgrastim, ICE-rituximab chemotherapy regimens, or monoclonal antibodies such as tyrosine kinase inhibitors (Sorafenib) useful for acute refractory/relapsed leukemia.These drugs are used as first salvage regimens or clofarabine and cladribine for acute myeloid leukemia in patients for whom combined anthracycline chemotherapy is inappropriate.

Angiogenesis is the process of new blood vessels formation that contribute to tumor growth and metastasis. Endothelial cell-selective adhesion molecule is one of the proteins that expresses in vascular endothelial cells. In vitro and animal studies have shown involvement of this protein in physiological and pathological angiogenesis. von Willebrand factor is a protein expressed by endothelial cells and megakaryocytes that has a role in blood clotting processes. In the current study, we investigate the expression of endothelial cell-selective adhesion molecule and von Willebrand factor in carcinoma mammae specimens and explore their correlation with tumor growth and metastasis.
We obtained 79 specimens from paraffin blocks of patients diagnosed with invasive breast carcinoma of no special type. The slides from these specimens were then stained with endothelial cell-selective adhesion molecule, von Willebrand factor, and Ki-67 antibodies to assess vascular numbers and cell proliferation.
We found a total of 31 (39%) low vascularity and 48 (61%) high vascularity samples from endothelial cell-selective adhesion molecule staining. There were 34 (43%) low vascularity and 45 (54%) high vascularity samples by von Willebrand factor staining. There was a significant correlation of blood vessel numbers in the endothelial cell-selective adhesion molecule-stained samples with tumor volume, metastasis to lymph nodes, and proliferation cells. The von Willebrand factor-expressed samples only had a significant correlation of vascular number with tumor volume.
Endothelial cell-selective adhesion molecule and von Willebrand factor as the endothelial cell expressed proteins play a role in the angiogenesis process of breast cancer. However, endothelial cell-selective adhesion molecule expression is more consistent than von Willebrand factor in predicting the presence or absence of metastatic breast cancer.

Esophageal squamous cell carcinoma is among the leading causes of cancer related deaths within gastrointestinal tumors. There is a growing body of evidence that shows an association between Epstein Barr virus infection and the development of malignancies such as B-cell non-Hodgkin’s lymphoma, Hodgkin’s disease, and Burkett’s lymphoma. However its potential association with esophageal squamous cell carcinoma is controversial. Therefore, in the present study, we have explored the association of Epstein Barr virus with pathological information and clinical outcomes of 108 esophageal squamous cell carcinoma patients.
There were 48% female and 52% male patients with a mean age of 59.2±11.1 years who enrolled in this study. Patients had the following tumor stages: T1 (5.6%), T2 (21.3%), and T3 (71.3%). A total of 32.4% had lymph node metastases. In order to explore whether patient characteristics might influence clinical outcome, we analyzed data on progression-free survival and overall survival according to patients’ clinicopathologic features.
An association existed between tumor size, node and metastasis status, and stage with shorter overall and progression-free survival. We observed that 6.5% of patients had Epstein Barr virus. All patients infected with Epstein Barr virus had T2 and T3 disease.
Our findings demonstrated the presence of Epstein Barr virus in 6.5% of Iranian patients and its potential link with tumor size. Additional studies in multicenter settings should be conducted to determine the association of Epstein Ba.

Glutathione reductase is an important enzyme in oxidative metabolism that provides reduced glutathione from its oxidized form in the cells. The role of oxidative stress in tumor tissues has led us to investigate the gene expression and activity of this enzyme in tumor and adjacent resected margins of colorectal cancer tissues, one of the most common malignancies in humans.
We conducted this study on 15 Iranian colorectal cancer patients. RNA was extracted from fresh colon tissues that included tumor and anatomically normal margin tissue. Expression of the glutathione reductase gene was determined using realtime PCR by the ΔΔCt relative quantification method. The gene expression results were standardized with glyceraldehyde 3-phosphate dehydrogenase as the endogenous reference gene. In addition, we measured enzyme activity of glutathione reductase with a commercial kit based on a colorimetric assay.
The tumor tissue had higher expression of glutathione reductase compared to the margin tissue (P=0.005). There was significantly greater glutathione reductase enzyme activity in the tumor tissue (116.9±34.31 nmol/min/ml) compared to the noncancerous adjacent tissues (76.7±36.85 nmol/min/ml; P=0.003).
These data showed increased glutathione reductase expression and enzyme activity in colorectal tumor tissue. Given the key role of glutathione in synthesis of dNTPs for DNA repair with the glutaredoxin system, the increased glutathione reductase expression and activity might be a reflection of hyperactivity of this enzyme in DNA synthesis and the repair process in colorectal cancer cells.

Breast cancer is the second leading cause of cancer death after lung cancer. Discovering molecular biomarkers is necessary for disease management that includes prognosis prediction and preventive treatment. The aim of this study is to evaluate the expression value of p53 and PTEN as molecular biomarkers of breast cancer and their relation with clinicopathological characteristics.
In this study, 100 breast cancer and 20 normal samples were subjected to investigation. Total RNA was isolated and we measured RNA expression by realtime RT-PCR. Data were analyzed by REST 2009 and SPSS.
Gene expression results showed up-regulation of P53 in 53 breast cancer subjects and PTEN in 52 breast cancer subjects compared with normal controls. However, there was lower P53 expression in 25 breast cancer samples compared to normal tissues. PTEN expression was lower in 26 breast cancer samples than normal tissues. p53 showed a significant relationship to HER2 receptor (P=0.024) and menopausal status (P=0.013); no significant relationships existed with other clinicopathological parameters (P>0.05). PTEN had the only significant correlation with lymphatic invasion (P=0.046) without any relation with other clinicopathological features (P>0.05). PTEN expression had no significant association with p53 expression in the studied population (P=0.074).
Combined detection of PTEN and p53 may have the potential to estimate the pathobiological behavior and prognosis of breast cancer. Due to the heterogeneous nature of cancer and the presence of different factors involved in the clinical situation of breast cancer, we suggest a study of a larger population and more biomarkers.

Placental growth factor is involved in human gastric cancer initiation and progression through stimulating the proliferation, angiogenesis, invasion and metastasis of cancerous cells. Previous studies indicate that the expression profiles of hsa-miR-22-3p, hsa-let-7b-3p, hsa-miR-451b, and hsa-mir-4290 change in MKN-45- derived gastric cancer stem-like cells. Therefore, this study aims to investigate the effect of PlGF knockdown on hsa-miR-22-3p, hsa-let-7b-3p, hsa-miR-451b, and hsa-mir-4290 expressions in MKN-45-derived gastric cancer stem-like cells.
We used a non-adhesive culture system to derive the cancer stem-like cells from MKN-45 cells. PlGF gene silencing was performed by PlGF-specific siRNA. The transcript of PlGF and miRNAs were measured by real-time RT-PCR. We conducted bioinformatics analyses with the online software programs TargetScan, miRanda, miRWalk, PicTar, and the Database for Annotation, Visualization, and Integrated Discovery tools to predict miRNAs’ targets and their signaling pathways.
hsa-let-7b-3p had a 2.28-fold up-regulation, whereas we observed downregulation of hsa-mir-451b (25%), hsa-mir-4290 (34%), and hsa-mir-22-3p (9%). Bioinformatics analysis results indicated that the miRNA target genes TGF-β, MAPK, and Wnt, and hedgehog signaling pathways contributed to cancer initiation and progression by influencing different cellular behaviors.
We suggest that PlGF signaling may influence miRNA expression profiles in MKN-45-derived cancer stem-like cells, which can influence the expressions of different genes and signaling pathways. However, more empirical studies should determine the exact effect of PlGF knockdown on the expression of miRNA targets in cancer stem-like cells to locate their actual gene targets.

Matrix metalloproteinases-2 and -9 play important roles in the development of breast cancer by hydrolyzing the extracellular matrix. Since −1306C/T and −1562C/T polymorphisms are located at the promoter regions of the matrix metalloproteinase- 2 and -9 genes, respectively, C to T substitution may affect promoter activity and impact the rate of extracellular matrix degradation and cancerous cell proliferation. Therefore, we aimed to determine the genotype and allele frequencies of these polymorphisms in Iranian healthy women and women with breast cancer. We have also examined the correlation of genotypes with clinicopathological parameters such as tumor type, tumor size, and metastasis to lymph nodes.
This case-control study enrolled 200 women with breast cancer and 200 age-matched healthy women. DNA was extracted, and we determined the genotype and allele frequencies of −1306C/T matrix metalloproteinase-2 and −1562C/T matrix metalloproteinase-9 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism method. Additionally, tumor size (20 mm), tumor type (ductal/non-ductal), and metastasis (yes/no) were determined.
Genotype and allele frequencies of the −1306C/T matrix metalloproteinase- 2 polymorphism showed no significant association with the occurrence of breast cancer. Genotype and allele distribution differed in the −1562C/T matrix metalloproteinase- 9 polymorphism and indicated a 4.83-fold increase in the risk of breast cancer for T allele carriers. There was no likelihood of any interaction found between the two polymorphisms and susceptibility to breast cancer. In addition, the −1562C/T matrix metalloproteinase-9 T allele showed an association with metastasis to lymph nodes but we observed no association between the −1306C/T matrix metalloproteinase- 2 polymorphism and clinicopathological features.
The ‒1562C/T matrix metalloproteinase-9 polymorphism is involved in the pathogenesis of breast cancer in Iranian women. The T allele may increase the risk of disease.

This study evaluates the predictive significance of salivary amylase, glutathione, lipid peroxides, and lactate dehydrogenase in the treatment of head and neck cancer patients who undergo curative radiotherapy/chemoradiotherapy.
The volunteers for the study included head and neck cancer patients that required curative radiotherapy/chemoradiotherapy. Patients provided saliva and blood samples before the start of radiation treatment and 24 h after the first radiation fraction of 2 Gy (before the start of the second fraction). Samples were assessed for the levels of blood and salivary amylase, glutathione, lipid peroxides, and lactate dehydrogenase by standard laboratory methods. Clinical tumor radioresponse was assessed one month after the completion of treatment as complete responders, partial responders, and nonresponders.
The results indicated a significant increase in the levels of amylase, lactate dehydrogenase, and lipid peroxides; and a concomitant decrease in the levels of glutathione P The results indicate that salivary lactate dehydrogenase can be a useful predictive marker to ascertain radiation-induced tumor regression in head and neck cancers.

The psychological distress is a kind of mental stress that people experience due to various causes. This study was performed aimed to investigate the psychological distress in cancer patients.
This cross-sectional study was performed during one year on the patients who referred to two academic hospitals of Mashhad University of Medical Sciences for treatment or follow-up. Psychological distress questionnaire was used to collect data. Results were analyzed using SPSS version 16. P The mean (±SD) age of participants was 54 ± 15.30 with a range from 18 to 89. The most common cancers were colorectal, gastro-esophageal and breast cancer. The mean distress thermometer score was 5 ± 2.99. Out of 256, 173 (67.7%) of patients scored 4 or higher. The distress thermometer scores were higher among females, rural residents, those receiving treatment within the month before, patients with insight of their illness, those with low level of education and low functional status, non-smokers and divorced patients. Among these, having insight of the illness, receiving treatment in the month before and low functional status were significantly related with the psychological distress score. The most prevalent cause of psychological distress among the participants was fatigue, being reported by 176 participant (68.8%), followed by pain (59.4%), difficulty in transportation (59.4%), anxiety (57.2%), sadness (50.4%), anger (44.5%), and depression (43.8%).
Due to higher rate of severe emotional distress in different types of cancer, particularly in women, rural patients, those with lower educational status and performance and also divorced and addicted people, it is important to pay more attention to these groups for decreasing emotional distress. It required supportive and relief measures including psychological methods and reducing pain to improve the performance of these patients.

Colorectal cancer susceptibility may correlate with the Klotho gene G-395A and C1818T polymorphisms. This study aims to evaluate the relationship between a Klotho single nucleotide polymorphism and IGF-1 with risk of colorectal cancer.
This study enrolled 60 colorectal cancer patients and 60 age-matched healthy persons who referred to Razi Hospital, Rasht, and Northern Iran in September 2013. Patients enrolled under supervision of a gastro-intestinal specialist and according to the ethics right. G-395A and C1818T polymorphisms were genotyped with polymerase chain confronting two pair primer technology. IGF-1 and certain biochemistry analytes were assayed. Statistical analysis was used to compare appropriate relationships.
There were different base pair partitions for G395A and C1818T. Odds ratio and 95% confidence interval were used to analyze the correlation of genotypes and haplotypes with colorectal cancer susceptibility. The AA (odds ratio: 1.437, 95% confidence interval: 0.596) and GA (odds ratio: 1.958, 95% confidence interval: 1.133- 3.385) genotypes of the G-395A polymorphisms showed a slight relationship to the risk of colorectal cancer. The A allele had a much higher frequency in the case group (31.2%) compared with the control group (17.6%). There was no significant relationship with the C1818T polymorphism between the case and control groups.
The Klotho gene polymorphism did not significantly increase the risk of colorectal cancer. Therefore, these genotypes might not have a correlation with IGF-1.

Follicular dendritic cell neoplasms are extremely rare. Information regarding the accurate treatment and prognosis is limited owing to their rarity; thus, this tumor encompasses a domain to be brought into focus. Clinical and pathological diagnoses warrant a high index of suspicion as this entity is not considered in routine clinical practice. Histopathologically it mimics various other neoplasms which lead to higher chances of misdiagnosis at initial evaluation. Use of follicular dendritic cell immunohistochemical markers CD 21 and CD 35 helps in rendering a definitive diagnosis.

Pineal region tumors are uncommon lesions in the central nervous system. Papillary tumor of the pineal region is recently recognized as a separate disease. Its incidence, treatment, and outcome are not well-defined. We have reported the case of a 6 yearold- boy with papillary tumor of the pineal region. He presented with headaches, nausea and vomiting and, after a biopsy, was referred for radiotherapy. The patient received 54 Gy irradiation to the pineal region followed by a chemotherapy regimen of cisplatin, vincristine, and lomostine. His tumor decreased slightly. After 4 years, the patient has remained well and attends school. He is under routine follow-up. We suggest radical radiotherapy as the main treatment for papillary tumors of the pineal region.