Iraqi Journal of Cancer and Medical Genetics

Bladder cancer is a complex disease and this study of bladder cancer was conducted to assess the significance of level difference of MMP-9 in urine and tissue biopsy which has a role in tumor progression in bladder cancer patients. MMP-9
evaluated in urine of 48 bladder cancer patients and 40 healthy controls by ELISA test, and in 57 biopsies of bladder cancer and 40 normal urothelium (autopsies) by immunohistochemistry (IHC). Result indicated that urine MMP-9 showed high specificity in diagnosis bladder cancer patients, and has a role in discrimination between (newly diagnosed vs recurrence), but urine level and tissue expression of MMP-9 were unrelated to grade, muscle invasion. Some risk factors like Schistosomiasis and family history of cancer showed a significant association with MMP-9 tissue expression.

Sixty males of the Albino rat Rattus norvegicus were used in this present study and divided to four groups. Each group was contained fifteen males. Three groups were injected intraperitoneal for 30 days with different of concentrations Aluminum Chloride AlCl3 and the fourth group was used as control. Animals were killed, and an autopsy was extracted micronuclei from its bone marrow in accordance with method of (Schmid,1975) [12]. And collected mitotic index through number of metaphase per 1000 lymphocyte was extracted from its bone marrow accordance with method of (Brusick,1980) [13]. The results showed significant increased, of micronucleus (MN) in treated rats with increasing concentrations of AlCl3 , in comparison with the control group at (p<0.05). As well was in the mitotic index (MI) in lymphocyte of bone marrow in comparison with the control group at the level of significance (p<0.05).

Thirty six samples were collected from patients suffering from wounds and burns in Baghdad Hospitals. The samples were analyzed for the presence ofStaphylococcus aureus. Ten positive samples screened by phenotypic microbiological and Biochemical tests and genotypic by DNA extracted from all isolates and the PCR carried out using 16S rRNA gene for S. aureus. In this method for identifying and confirmed all the staphylococcal isolates as S. aureus.The present study was carried out in an attempt to detect the distribution of antibiotic-resistant and we have tried to cover the ever increasing problems facing the treatment and containment of bacterial skin infections. Therefore we are study Susceptibility of Staphylococcus aureus to antibiotics. The results showed relatively high resistance to MethcillinME ,Amoxicillin-Clavilonicacid, Azithromycin with frequencies of 100%, 100% and 70% respectively and moderate resistance to Vancomycin VA, Amikacin AK with frequencies of 60% and 62% respectively, low resistance to Fusidic acid with frequencies of 30% because that we determined the Minimum Inhibitory Concentration for Fusidic acid, the isolates incorporated in this test were those have intermediate resistant to Fusidic acid.

Cyproheptadine hydrochloride is an antiserotonergic and antihis-taminic agent that can indicate allergic diseases there for it is used for treating symptoms of allergic reactions in addition to its sedative and anti cholinergic effects, Cyproheptadine is also used to stimulate appetite and weight gain in human and veterinary medicine Considering its potentially dangerous for human health. therefore, this study aimed to assess the effect of (25μg/kg) and (50μg/kg) of cyproheptadine, given to mice by “gavage” and observe cytogenetic effects (DNA damage) on mice bone marrow cells (in vivo) by using comet assay. The statistical analysis shows that cyproheptadine hydrochloride cause significant increase (P≤0.0001) of DNA damage of bone marrow cells in mice in comparing with the negative controls. The DNA damages are detected by the comet assay test in mice treated with Cyproheptadine hydrochloride. The prolonged use of Cyproheptadine hydrochloride led to increase the probability of DNA damage.

Background: beta thalassemia major is a big health problem worldwide. There are few studies dealing with prevalence and nature of thyroid dysfunction in Iraq.
Objectives: to establish the prevalence of thyroid dysfunction among patients with beta thalassemia major.
Patients and Methods: this study was conducted during Nov. 2013 and dealt with 73 Iraqi patients with beta thalassemia major attending Al-Karma thalassemia Centre in Baghdad. They included 40 males and 33 females with age ranged from 15 years to 30 years. The height and weight were measured. Thyroid function tests were performed by enzyme linked fluorescent antibodies.
Results: hypothyroidism were reported in 16 patients 10 males and 6 females out of 73 patients examined with prevalence rate of 21.9%. All cases of hypothyroidism were subclinical hypothyroidism (high TSH level with normal T4 and T3).No case was documented to have autoimmune thyroiditis.
Conclusion: there is high prevalence of thyroid dysfunction among Iraqi patients with beta thalassemia major. It is of high importance to monitor those patients at yearly intervals for early detection and replacement therapy.

Background: Breast cancer is the most frequent cancer and cause of death among women worldwide. ABCG2 (ATP–binding cassette sub-family G member 2) is an ABC transporter superfamily and endogenous expression of ABCG2 in different certain cancer reflect intrinsic drug resistance. It is also a molecular determinant of pharmacokinetic properties of many drugs in humans. In this study, we determined the expression levels of ABCG2 in breast tissues of Iraqi women with stage II and III breast cancer. The correlation between the expression levels of ABCG2 and clinicopathological features was analyzed.
Methods: The expression levels of ABCG2 in the breast was determined by using real- time PCR and immunohistochemistry in 64 patients with stage II and III samples and in 21 benign tumors from Iraqi women.
Results: We found that the expression level of ABCG2 mRNA were significantly increased in breast cancer stage II-III tissues than those in benign tumor tissues. There was a significant variation between the mRNA levels of ABCG2 in stage II and stage III at P< 0.05. Immunohistochemistry revealed that the protein expression levels of ABCG2, was also increased in 83% of patients with stage II and III breast cancer as compared to 17% in benign tumor. The increased expression levels of ABCG2, in stage II-III breast cancer were correlated to tumor stages (P=0.03), tumor grades (P=0.01), tumor types (P=0.01) and lymph node metastasis (p=0.0001), respectively.
Conclusion: ABCG2 expression level in Iraqi women with stage II and III breast cancer were highly correlated with tumor stages, grades, types and metastasis and they could be used a potential markers which can prediction tumor behavior, progression and prognosis. Over expression of ABCG2 protein lead to treatment failure, tumor relapse and tumor metastasis by induction cancer cells against cytotoxic drugs.

Background: The transcription factor forkhead-box protein P3 (FOXP3) have been identified to counteract the anti-tumor immune responses during tumor progression. In addition, by expressing FOXP3, tumor cells may evade effector T-cell responses, resulting in a survival benefit of the tumor.
Objectives: Evaluation of the diagnostic and/or prognostic values of FOXP3 gene in breast cancer Iraqi female patients by initially comparing the expression concentrations of this gene between breast cancer patients and control group, then, comparing the expression levels of FOXP3 with certain clinical features among breast cancer patients (ages of patients, tumor grade, tumor stage and the presence or absence of metastasis).
Material and Methods: The Foxp3 levels were determined in tissue samples (Formalin Fixed Paraffin Embedded Tissue “FFPE”) derived from 51 Invasive Ductal Carcinoma women and 33 benign breast tumor women (control group) were attended to the Medical City and Al-Yarmouk teaching laboratories / Baghdad – Iraq. The patients’ samples were subjected to total RNA extraction, and then to molecular study by using reverse transcription and quantitative real time PCR at Molecular Oncology Unit in Guy´s Hospital – Kings College / London – UK.
Results: The FOXP3 gene expression was detected in 45 (88.23%) of breast cancer patients, also, the expression levels of this gene showed high significant increase in breast cancer patients compared to control group. Furthermore, there were a gradual increase in the FOXP3 expression concentrations with disease grades (highly significant) and stages (significant) progression in patients with primary breast cancer, moreover, the metastatic breast cancer patients showed high significant increase in FOXP3 levels compared to primary breast cancer patients. There were no significant differences in the levels of FOXP3 among the age groups of patients.
Conclusions: The present study results reflect the potential utility of FOXP3 as noninvasive marker for detecting breast cancer even in the earliest cancer stages, also, they suggest that possibility of using this gene as an efficient molecular signature for detecting breast cancer disease progression, discrimination between different stages and grades of breast tumors, and it might be of value as a prognostic marker.

Background: metalloproteinase-7 (MMP-7) is produced by stromal cells and by tumor cells,and overexpressed in a variety of epithelial and mesenchymal tumors. The aim of this study was to assessthe association of MMP-7 with clinical pathological factors and to evaluate its diagnostic value in patients with bladdercarcinoma.
Methods: Expression of MMP-7 was evaluated in tumor tissues of 32 urinary bladder cancer cases and 30 control groups were fixed in formalin and embedded in paraffin blokes, then analyzedby in situ hybridization technique.
Results: Expression of MMP-7 was significantly higher in tumor compared to normal samples. The expression significantly associated with tumor grade and muscle invasion.
Conclusion: MMP-7 may play an essential role in pathogenesis of bladder cancer. And may helpful to conventional diagnostic tools in malignancy as diagnosis.

Background: The Natural cytotoxicity receptors (NCR1 and NCR3) have been classically defined as activating receptors
delivering potent signals to Natural Killer (NK) cells in order to lyse harmful cells and to produce inflammatory cytokines.
Indeed, the elicitation of NK cells effector functions after engagement of NCRs with their ligands on tumor cells without the need for prior antigen recognition is one of the main mechanisms that allow a rapid clearance of tumor cells.
Objectives: Evaluation of the diagnostic and/or prognostic values of NCR1 and NCR3 genes in breast cancer Iraqi females patients by initially comparing the expression concentrations of these genes between breast cancer patients and control group, then, comparing the expression levels of these genes with certain clinical features among breast cancer patients (ages of patients, tumor grade, tumor stage and the presence or absence of metastasis).
Material and Methods: The NCR1 and NCR3 levels were determined in tissue samples (Formalin Fixed Paraffin Embedded Tissue “FFPE”) derived from 51 Invasive Ductal Carcinoma women and 33 benign breast tumor women (control group) were attended to the Medical City and Al-Yarmouk teaching laboratories / Baghdad – Iraq. The patients’ samples were subjected to total RNA extraction, and then to molecular study by using reverse transcription and quantitative real time PCR at Molecular Oncology Unit in Guy´s Hospital – Kings College / London – UK.
Results: The expression of NCR1 and NCR3 genes were detected in 43 (84.31%) and 41 (80.39%) of breast cancer patients respectively, also, the levels of these genes showed high significant increase in breast cancer patients compared to control group. Furthermore, there were a gradual increase in the NCR1 and NCR3 expression concentrations with disease grades and stages progression (significant for both genes) in patients with primary breast cancer, moreover, the metastatic breast cancer patients showed significant decrease in NCR1 and NCR3 levels compared to primary breast cancer patients. There were no significant differences in the levels of NCR1 and NCR3 genes among the age groups of patients.
Conclusions: The present study results reflect the potential utility of NCR1 and NCR3 as noninvasive markers for detecting breast cancer even in the earliest cancer stages, also, they suggest the possibility of using these genes as an efficient molecular signatures for detecting breast cancer disease progression, discrimination between different stages and grades of breast tumors, and its might be of value as a prognostic markers.

Hematopoietic stem-cell transplantation (HSCT) refers to a procedure in which hematopoietic stem cells are infused to restore bone marrow function in cancer patients who receive bone-marrow-toxic doses of cytotoxic drugs, with or without whole-body radiation therapy. Stem cells may be obtained from the transplant recipient (autologous HSCT) or can be harvested from a donor (allogeneic HSCT). Stem cells may be harvested from bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates. The perception of the mechanisms through which malignant cells are eradicated following allogeneic hematopoietic cell transplantation (HCT) has evolved substantially over the past four decades. No longer merely thought of as a means to rescue hematopoietic function following myeloablative conditioning, allogeneic transplantation is now known to be a powerful type of immunotherapy capable of curing patients with other-wise fatal malignant diseases. This conceptual evolution has translated into a diversification of the indications for allotransplants and led to the development of reduced intensity transplant approaches whose beneficial antineoplastic effects occur as a consequence of the transplanted donor immune system. Recently, investigators have begun to test whether non-hematologic malignancies might likewise be susceptible to allogeneic immune attack.

Aim: To investigate the possible association between human papillomavirus (HPV) and endometrial carcinoma. Does HPV play any role in the initiation or prognosis of endometrial adenocarcinomas among Iraqi women patients.
Method: To determine the relationship between HPV and endometrial carcinoma , a retrospective study was done. The study was carried out on 30 patients with hisopathologically confirmed primary endometrial adenocarcinoma ,samples were collected from each patients , as well as twenty (20) endometrial tissues from control individuals with no cancer. Chromogen In situ hybridization (CISH) was used to detect HPV DNA genotype 16 /18 in endometrial tissues.
Results: HPV 16/18 was detected in 19/30 (63.3%) tumor sample while negative cases were 11/30 (36.7%) of tumor sample and HPV 16/18 was detected in 5/20(25.0%) of endometrial control group while negative in 15/20 (75.0%) cases of endometrial control group.
Conclusion: Our results revealed that high risk of HPV(16 / 18 ) being the most frequent type in Iraqi women patients with endometrial adenocarcinoma. Association between HPV infection and endometrial adenocarcinoma was observed and this research considered the first study which evaluated score ,intensity and pattern of replication system of HPV by using CISH technique which reflected role of HPV in endometrial carcinogensis.

Liver cancer is the sixth most frequent cancer and the second leading cause of cancer death through the world. The first
objective of the present study is to know the chromosomal aberrations in peripheral blood of liver cancer patients. The
present study was carried out on 50 patients who were suffering from liver cancer in Erbil city and 25 healthy individuals as a healthy group in both sex and different age groups. The second objective of the present study is to know the mutations in TP53 tumor suppressor gene, so molecular study was carried out on 18 patients who were suffering from liver cancer in Erbil city and 1 healthy individual as a control group. Detection a mutation in TP53 gene in peripheral blood cells may be helpful to the diagnosis of liver cancer, especially to the accurate staging of liver cancer. Additionally, cytogenetic study followed by molecular analysis of recurring chromosome changes has facilitated the identification of crucial ontogenesis and tumor suppressor genes. The mechanism of liver carcinogenesis involve multiple endogenous and exogenous genetic alterations, so many factors contribute to its development such as genetic factors, Hepatitis Band C virus infections, smoking habit and alcohol habit. Other factors was also studied included patient gender and age. The results of the present study suggest that highest value of chromosomal aberrations was (Dicentric chromosome) which occurred in males at fifth age group (65-74) , also shown that most patients are males at age group (65-74), most of them have smoking , alcohol habit and Hepatitis B viral infection . From the study of TP53 gene, we observed mutation in exon 7 which was deletion of nitrogen base G , just before the coding region , which represent splice- site mutation.

Peripheral blood samples were obtained from thirty three leather tannery workers directly involved in the tanning process in the tanning factory at Al- Zaafarniya / Baghdad , one of the factories of state company for leather tanning industries. In addition peripheral blood from twenty healthy control individuals (not known to be exposed to chemicals or other potentially genotoxic substances) were used as control group. The micronucleus (MN) assay was performed using the cytochalasin B technique. We observed a highly significant increase in the mean frequency of lymphocyte micronuclei (MN) and nucleoplasmic bridges (NPBs) , a significant increase in the mean frequency of nuclear buds (NBUDs) and a highly significant decrease in the mean frequency of nuclear division index (NDI) of the tannery workers group in comparison with the control group. The results of the present study also indicate the influence of service duration of tannery workers in lymphocyte MN , NPB, NBUD and NDI frequencies . The age of tannery workers also effect in lymphocyte micronuclei and nuclear division index frequency. The conclusion from our study that the tannery factory workers studied have experienced genotoxic exposure, which is manifested as an increase in the frequency of lymphocyte MN, NPB, NBUD and a decrease in NDI this work shows a clear genotoxic effect. Our study recommends providing all occupational safety requirements for workers in the factory and commitment of workers apply them.

Background: Chronic myelogenous leukemia( CML) is a type of leukemia in about 20 % of all types of leukemia. It is a malignant clonal, myeloproliferative disorders of the pluripotent hematopoietic stem cells. Aim of study:The present study was aimed to determine in vitro the cytotoxic effect of imatinib on normal myeloid stem cells and leukemic myeloid cells of patients with chronic myelogenous leukemia.
Materials and methods: Imatinib was prepared by serial dilution in concentrations (250, 125, 62.5, 31.25, 15.625,7.8125 μg/ ml ), it was added to the cells culture. Using MTT assay.
Results: The results show the cytotoxic effect (inhibition rate of growth) of imatinib was in dose and time dependent.There were significant differences between concentrations and time exposure (24,48,72 hr). The highest inhibition rate on the leukemic cells was 89.907% in concentration 250μg/ml and the lowest inhibition was 43.918 % in concentration 7.8125 μg/ml for exposure time 72hr While the highest inhibition rate on the normal myeloid cells was 34.621 % in concentration 250μg/ml and the lowest inhibition was 14.588 % in concentration 7.8125 μg/ml for exposure time 72hr.
Conclusions: imatinib has a highly inhibited growth for the leukemic myeloid stem cells and less inhibited for the normal cells.This is a guide for choosing any drug with high cytotoxic effect on the leukemic cells and less cytotoxic effect on the normal cells.