Faisel Abu-Duhier

Pharmacological Intervention through Dietary Nutraceuticals in Gastrointestinal Neoplasia

Neoplastic conditions associated with gastrointestinal (GI) tract are common worldwide with colorectal cancer alone accounting for the third leading rate of cancer incidence. Other GI malignancies such as esophageal carcinoma have shown an increasing trend in the last few years. The poor survival statistics of these fatal cancer diseases highlight the need for multiple alternative treatment options along with effective prophylactic strategies. Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high intake of certain dietary agents in their regular meals have lower cancer rates. Thus, an impressive embodiment of evidence supports the concept that dietary factors are key modulators of cancer including those of GI origin. Preclinical studies on animal models of carcinogenesis have reflected the pharmacological significance of certain dietary agents called as nutraceuticals in the chemoprevention of GI neoplasia. These include stilbenes (from red grapes and red wine), isoflavones (from soy), carotenoids (from tomatoes), curcuminoids (from spice turmeric), catechins (from green tea), and various other small plant metabolites (from fruits, vegetables, and cereals). Pleiotropic action mechanisms have been reported for these diet-derived chemopreventive agents to retard, block, or reverse carcinogenesis. This review presents a prophylactic approach to primary prevention of GI cancers by highlighting the translational potential of plant-derived nutraceuticals from epidemiological, laboratory, and clinical studies, for the better management of these cancers through consumption of nutraceutical rich diets and their intervention in cancer therapeutics.

Potential Impact of Vascular Endothelial Growth Factor Gene Variation (-2578C>A) on Breast Cancer Susceptibility in Saudi Arabia: a Case-Control Study

Aim: VEGF gene polymorphisms can induce either increase or inhibition of VEGF secretion, with altered promoter activity. The VEGF rs699947 SNP is located in the promoter region and is associated with susceptibility to breast carcinoma development. Here, we investigated the association of the -2578C>A polymorphism in the VEGF gene with breast cancer risk in Saudi women. Methodology: Genotyping of the VEGF-gene variation (-2578A>C) was performed using the amplification refractory mutation system PCR. We investigated the association of VEGF gene variants with different clinicopathological features of breast cancer patients. Results: A significant difference was observed in genotype distribution among the breast cancer cases and sex matched healthy controls (p=0.03). The frequencies of the three genotypes CC, CA, AA found in the patient samples were 37%, 45% and 18% and in the healthy controls were 54%,37%, and 09% respectively. An increased risk of developing breast cancer in Saudi women was associated with the VEGF −2578 AA genotype (OR = 2.91, 95 % CI, 1.18-7.20; p = 0.01; RR 1.78 (1.01-3.11 p=0.01), the VEGF −2578 A allele (OR = 1.79, 95 % CI, 1.17-2.73; p = 0.004: RR 1.35 1.07-1.71) and the VEGFR-(CA+ AA) (OR 1.99 1.13-3.51; RR 1.401.0-1.85). Thus the A allele increased the risk of BC when compared with C allele. When we stratified groups of patients according to the status of tumor markers, stage, age and metastasis, statistically significant associations with −2578 C/A SNP were revealed. Conclusion: Our data showed a significant association of the VEGF -2578C>A polymorphism with BC susceptibility in Saudi women. The VEGF -2578AA homozygote significantly increases the risk and can be useful as a predisposing genetic marker. Further studies with larger sample sizes are necessary to confirm our findings.

Whole Genome Sequencing in an Acrodermatitis Enteropathica Family from the Middle East

We report a family from Tabuk, Saudi Arabia, previously screened for Acrodermatitis Enteropathica (AE), in which two siblings presented with typical features of acral dermatitis and a pustular eruption but differing severity. Affected members of our family carry a rare genetic variant, p.Gly512Trp in the SLC39A4 gene which encodes a zinc transporter; disease is thought to result from zinc deficiency. Similar mutations have been reported previously; however, the variable severity within cases carrying the p.Gly512Trp variant and in AE overall led us to hypothesise that additional genetic modifiers may be contributing to the disease phenotype. Therefore whole genome sequencing was carried out in five family members, for whom material was available to search for additional modifiers of AE; this included one individual with clinically diagnosed AE. We confirmed that the p.Gly512Trp change in SLC39A4 was the only candidate homozygous change which was sufficiently rare (ExAC allele frequency 1.178e-05) and predicted deleterious (CADD score 35) to be attributable as a fully penetrant cause of AE. To identify other genes which may carry relevant genetic variation, we reviewed the relevant literature and databases including Gene Ontology Consortium, GeneMANIA, GeneCards, and MalaCards to identify zinc transporter genes and possible interacting partners. The affected individual carried variants in RECQL4 and GPAA1 genes with ExAC allele frequency <0.01 and CADD score >10. p.Gly512Trp is highly likely to be the pathogenic variant in this family. This variant was previously detected in a Tunisian proband with perfect genotype-phenotype segregation suggestive of pathogenicity. Further research is required in this area due to small sample size, but attention should be given to RECQL4 and GPAA1 to understand their role in the skin disease.

A Germline Mutation in the BRCA1 3’UTR Variant Predicts Susceptibility to Breast Cancer in a Saudi Arabian Population

Purpose: The impact of the BRCA1-3’UTR-variant on BRCA1 gene expression and altered responses to external stimuli was previously tested in vitro using a luciferase reporter assay. Its ability to predict breast cancer risk in women was also assessed but the conclusions were inconsistent. The present study concerns the relationship between the BRCA1-3’UTR germline variant rs8176318G>T and susceptibility to Breast cancer in an ethnic population of Saudi Arabia. Methodology: The study included 100 breast cancer patients and 100 sex matched healthy controls from the northwestern region (Tabuk) and Dammam of Saudi Arabia were investigated for the BRCA1-3’UTR germline variant rs8176318G>T using an allele specific PCR technique. Genotype distributions were then compared. Results: The frequencies of the three genotypes GG, TT and GT in our Saudi Arabian patients were 26%, 8% and 66% and in healthy controls were 45%, 5% and 50%, respectively (p=0.03). Risk of developing breast cancer was found to be significantly associated with the GT variant (OR 2.28, 1.24-4.191; RR 1.47, 1.11-1.93; P=0.007), GT+TT (OR, 2.32, 1.28-4.22; RR 1.48, 1.13-1.94; P=0.005) and the T allele (OR 1.62, 1.072- 2.45; RR 1.28, 1.02-1.60: P=0.020). There were 2.76 and 2.28 fold increase risks of developing breast cancer associated with the TT and GT genotypes in our cases. A significant correlation was also found between the BRCA1 3’UTR variants with the stage of the disease and distant metastasis but not with age, grade, and ER, PR and her2/neu status. Conclusion : The rs8176318G/T in the 3’untranslated region (UTR) of the BRCA1 gene was found to be associatedwith increased susceptibility to breast cancer in our study population, increased risk being noted with the GT and TT genotypes. Further association studies are needed to confirm this finding in other regions of Saudi Arabia.

Clinical Significance of Circulatory miRNA-21 as an Efficient Non-Invasive Biomarker for the Screening of Lung Cancer Patients

Dysregulation in the miRNA-21 expression has been previously observed in a number of malignancies and not only in the tumor cell itself but also in the body fluids of the cancer patients. The present study aimed to find out the clinical significance of cell-free circulating miRNA-21 as an efficient non-invasive biomarker for the screening of lung cancer patients. The present case-control study included plasma samples from 80 lung cancer patients and 80 healthy controls. Magnetic bead technology was used for efficient miRNA isolation and advanced TaqMan miRNA assays were used for the quantification of miRNA-21 level in the plasma of the lung cancer patients and healthy individuals. The overall mean relative expression level of plasma miRNA-21 among lung cancer patients (2.32±1.7) was higher when compared to healthy individuals (0.715 ± 0.48) and it showed a significant difference of p<0.0001. The area under ROC curve was 0.8913 [95% confidence interval (CI): 0.8394 to 0.9431, p< 0.0001] and the sensitivity and specificity were both 80.0% when the cut-off value was 1.207. In conclusion, plasma miRNA-21 can be efficiently extracted by the magnetic bead technology and quantified by the advanced TaqMan miRNA assay. Plasma miRNA-21 showed a high ability to distinguish between lung cancer patients and healthy individuals, therefore can be used as an efficient non-invasive biomarker for the screening of Lung cancer patients.

GSTT1 (rs4025935) null genotype is associated with increased risk of sickle cell disease in the populations of Tabuk—Northwestern region of Saudi Arabia

ABSTRACT Background: Glutathione system plays an important role in the protection of cells and tissue against damage from oxidative stress. Impairment of the glutathione system due to genetic polymorphism of GST genes may increase the risk and severity of sickle cell disease (SCD). Present study was, therefore, undertaken to examine the relative impact of the genetic polymorphism of GSTT1 and GSTM1 (rs4025935 and rs71748309) on susceptibility and hematological aspects of the patients with SCD. Methods: Present study included 100 patients with SCD and 200 healthy controls from northwestern region of Saudi Arabia. GSTM1 and GSTT1 (rs4025935 and rs71748309) genotypes were investigated by using single-tube multiplex PCR technique. Results: It was observed that patients with SCD possessed significantly higher frequency of GSTT1 null genotype (26%) than healthy controls (15%), (P = 0.00001). Compared to the presence of GSTT1 genotype, the OR for the GSTT1 null genotype were estimated to be 4.3 (2.17–8.64, P = 0.00001). However, such association was not observed with respect to the presence of GSTM1 null genotype. In addition, it was observed that SCD in patients with GSTT1 genotype, the mean percentage levels for HbF and HbS were 0.48 and 35.4%, respectively; however, among SCD patients with GSTT1 null genotype, the mean percentage levels were significantly higher 1.62% (P = 0.004) and 39.38% (P = 0.02), respectively. Conclusion: GSTT1 null genotype is significantly associated with increased risk of SCD among the population of northwestern region of Saudi Arabia. In addition, it may be one of the important factors responsible for hematological manifestations of SCD.

Dietary Factors May Influence the Clinical Outcome of Chemotherapy in Cancer Multidrug Resistance

A substantive burden of cancer mortality results from poor prognosis of the disease due to the failure of chemotherapeutic regimen under the influence of Multidrug Resistance (MDR). The outcome of chemotherapy which is the most effective treatment for patients with cancer is impeded by the development of drug resistance. Anticancer drugs can fail to kill cancer cells for various reasons that include variations in the absorption, metabolism, and delivery of drug to target tissues and tumor location in parts of the body into which the drugs do not easily penetrate. In addition, certain cancer cells develop resistance by micro-evolutionary means through mutations occurring in the drug target, thus rendering the drugs ineffective. However, the most common of these mechanisms is the efflux of hydrophobic drugs mediated by energy driven ATP-binding cassette (ABC) family of transporters such as P-glycoprotein (P-gp), an integral membrane protein over-expressed in several malignancies. Various generations of MDR modulators have presented novel and improved interventions, though not to the perfection. Studies have shown that natural compounds found in vegetables, fruits, plant-derived beverages, and herbal dietary supplements not only have anticancer properties but may also modulate P-gp activity. P-gp inhibitors found in natural products, especially those found in plants of dietary origin and traditional medicine, have the potential to be developed as MDR reversing agents as adjuvant to chemotherapy leading to better clinical prognosis.

The Effectiveness Of Cardio-Pulmonary Resuscitation Using High Fidelity Mannequin And Standard Method Among The Selected Students In Faculty Of Applied Medical Sciences,University Of Tabuk

Introduction: Hypertension is a major risk factor for cardiovascular disease, and for hypertensive patients to avoid complications and increase their quality of life its control is important. Factors affecting hypertension control might be not limited to the individual. In this study we review existing studies of factors related to hypertension control and evaluate these on four levels: individual, work/ family, community, and social. As the impact of factors may also differ between males and females, the effects of various factors on hypertension control were analyzed according to sex.Results: Four themes emerged from the data (1) CC was considered a ‘silent disease’ that could be detected with early screening. It was associated with extra marital sexual relations which had a negative impact on screening uptake. (2) Fear, pain, embarrassment of screening as well as cultural influences rather than religious beliefs negatively influenced uptake. (3) There was growing mistrust of allopathic medicine and impersonal influences in health care which negatively affected screening uptake and (4) Women who had been screened had little understanding of the causes of CC and only became aware of screening when they were pregnant or receiving fertility treatment.Background: It is a well-known fact that sudden cardiac arrest is the leading cause of death in the world. During such situations nurses are expected to be efficient and effective in the life saving measures. Objective: This quasi-experimental study was aimed to evaluate the effect of high fidelity simulation on the students learning of Cardio Pulmonary Resuscitation. Methods: The knowledge instrument composed of 20 items (multiple choices) and the skills were observed by the 10 items (checklist) using 4-point likert scale. An experimental group attended lecture and practice training with Sim man 3G mannequin whereas the control group attended lecture and the practice training with the standard mannequin. Results: Independent t test showed a statistically significant difference in psychomotor retention in control group (t = 2.31. sig .030 (2 tailed), p> 0.05) between the immediate (M = 2.96, SD = .43) and delayed (M = 2.65, SD = .20) in teaching CPR. The result also gives significance difference between the experimental and control both for the immediate and delayed psychomotor test (t=6.96, sig..000, p˂0.05, 13.19 , t=13.9, sig. .000, p˂0.05 respectively) when examined the effect of the psychomotor between the experimental and control group in teaching CPR. Conclusion: The students who were trained with high fidelity mannequin performed better than the standard mannequin. This study emphasize on the incorporation of high fidelity simulation in the nursing program to enhance the knowledge and psychomotor skills of the students.T knowledge and skills required of today’s healthcare professionals far exceed expertise in traditional competency areas. The proper management of complex health conditions demands coordination of care by various health professionals. A multidisciplinary healthcare team supports the concept of leadership and teamwork as an essential component for success. There’s increasing evidence showing that clinical leadership is associated with high-performing healthcare organisations. Historically, these concepts have received relatively little attention in undergraduate curricula. In this presentation, the need of developing leadership courses, and to bring healthcare team members at one platform at an early stage will be explored. In addition, ways through which leadership and management theories, concepts and approaches can be utilised to develop such programs will be addressed. There are some key areas to focus upon, such as: 1) Leadership theory and practice, 2) Emotional Intelligence, 3) Setting Personal goals, 4) Setting vision and strategic direction, 5) Adaptive leadership, and 6) Understanding individual and organisational responses to change.Research Methodology: In this descriptive-correlative investigation, 95 members of the Association of Spinal Cord Injuries in Tehran were selected by simple random sampling method. Their quality of life and post-traumatic growth were studied in different aspects using France and Powers’ Questionnaire of Quality of Life Index for Spinal Cord Injury and Standard Questionnaire of Posttraumatic Growth Scale. Analysis of the data was performed with the help of SPSS 16 software utilizing descriptive and analytic statistical tests.Background: The distressing treatment of cancer whether chemotherapy or radiotherapy is associated with fatigue and has negative impact on patient quality of life (QOL). Objectives: The purposes of this study were to examine the impact of radiotherapy treatment on Jordanian cancer patients’ QOL and fatigue, and to explore the relationship between fatigue and QOL. Methods: One group quasi-experimental correlational design was used with 82 patients who had been diagnosed with cancer and required radiotherapy treatment. QOL was measured using the Functional Assessment of Cancer Therapy-General (FACT-G). Fatigue was measured using Piper Fatigue Scale (PFS). Data were collected over a period of three months, and analyzed using Pearson Product Moment Correlation, descriptive statistics and paired-sample t-test. Results: Significant differences were found between pre- and post- radiotherapy QOL mean total scores (t=19.3, df=79, P<0.05), as well as physical, emotional, sexual, and functional wellbeing dimensions. Statistically significant differences were found between pre- and post- radiotherapy fatigue mean total scores (t=-8.95, DF=79, P<0.05), as well as on behavioral, affective, sensory, and cognitive dimensions of PFS. Quality of life total scores correlated significantly and negatively with total fatigue scores (P<0.01). Conclusions: Exposure of cancer patient to radiotherapy treatment increased their fatigue level and decreased their QOL. Nurses should assess cancer patients before, during, and after their treatment to design proper interventions to reduce fatigue and enhance QOL.cause of death in women worldwide. In Saudi Arabia, breast cancer ranks first among cancerous diseases in females. Objectives: To investigate the level of breast cancer awareness among Saudi females in Tabuk, focusing on the knowledge of breast cancer signs, associated risk factors and breast self-examination. Methods: Crosssectional survey of 400 women attending the outpatient clinics of King Khalid Hospital in Tabuk city was carried out between 15 July and 30 August 2015 using self-administered questionnaire. Results: 35% of the Participants in this study aged between 26 and 35 years. The most widely known risk factor for breast cancer was family history (50%). The lowest level of knowledge of risk factor was regarding early menarche (3%) and late menopause (4%) and old age (14%). Other risk factors got moderate response, including lack of breast feeding, smoking, obesity (48%, 38%, and37.5%, respectively). Most of the participants (97.5%) identified breast mass as a symptom for breast cancer. However, nonlump symptoms were also known and more than half of the participants were aware of other warning signs such as bloody nipple discharge, skin change, change or retraction of nipple and change in shape/size of breast, accounting for 90%, 75 %, 71 %, and 68% respectively. Furthermore, as many as 71% of subjects identified breast self examination as an early detection measure for breast cancer. 98% of the Participants mentioned that they heard about breast self-examination (BSE). Only 74% of the participants correctly identified that BSE should be performed monthly but 38% had performed it. Conclusion: This study has shown that the participants have poor knowledge about breast cancer and its associated risk factors as well as breast self examination.