Abdulla Behbehani

Raf Kinase Inhibitor Protein RKIP Enhances Signaling by Glycogen Synthase Kinase-3β

Raf kinase inhibitory protein (RKIP) is a physiologic inhibitor of c-RAF kinase and nuclear factor κB signaling that represses tumor invasion and metastasis. Glycogen synthase kinase-3β (GSK3β) suppresses tumor progression by downregulating multiple oncogenic pathways including Wnt signaling and cyclin D1 activation. Here, we show that RKIP binds GSK3 proteins and maintains GSK3β protein levels and its active form. Depletion of RKIP augments oxidative stress-mediated activation of the p38 mitogen activated protein kinase, which, in turn, inactivates GSK3β by phosphorylating it at the inhibitory T390 residue. This pathway de-represses GSK3β inhibition of oncogenic substrates causing stabilization of cyclin D, which induces cell-cycle progression and β-catenin, SNAIL, and SLUG, which promote epithelial to mesenchymal transition. RKIP levels in human colorectal cancer positively correlate with GSK3β expression. These findings reveal the RKIP/GSK3 axis as both a potential therapeutic target and a prognosis-based predictor of cancer progression.

CT features in abdominal tuberculosis: 20 years experience.

BackgroundAbdominal tuberculosis (TB) is endemic in the developing world and is reemerging in the West. Since computed tomography (CT) has the ability to demonstrate changes in the peritonium, mesentry, lymphnodes, bowel and solid organs and is being increasingly used for primary evaluation of abdominal conditions, it is important to be familiar with the CT features of the disease.MethodsCT findings were retrospectively analysed in 49 patients with proved abdominal TB. Patients with genitourinary TB and with AIDS/HIV were not included in the study.ResultsPeritoneal involvement was the most common feature (77.5%) with ascites (wet peritonitis) seen in more than half the cases (55.2%). The rest showed peritoneal, mesenteric or omental thickening or mass formation but no ascites (dry peritonitis). Other findings included lymphadenopathy (46.9% mainly of diffuse nature, bowel wall thickening (38%) and solid organ involvement (20.4%).ConclusionsCT reliably demonstrates the entire range of findings which need interpretation in the light of clinical and laboratory data.

Raf kinase inhibitor protein: mechanism of loss of expression and association with genomic instability.

Aims: Raf kinase inhibitory protein (RKIP; also known as PEBP, for phosphatidylethanolamine-binding protein) is an endogenous inhibitor of the Raf– MAPK kinase (MEK)–MAP kinase pathway. It has emerged as a significant metastasis suppressor in a variety of human cancers including colorectal cancer (CRC) and was recently shown to regulate the spindle checkpoint in cultured cells. This study aims at correlating RKIP expression with chromosomal instability in colorectal cancer samples and identifies possible mechanisms of RKIP loss. Methods: Chromosomal instability was assessed using metaphase-based comparative genomic hybridisation (CGH) and loss of heterozygosity (LOH) in 65 cases with microsatellite stable CRC and correlated with RKIP expression. Methyl-specific PCR was used on DNA extracted from 82 cases with CRC to determine CpG methylation status at the RKIP promoter and the results correlated with RKIP protein expression. Results: We demonstrate for the first time that in microsatellite stable (MSS) CRC, the number of chromosomal losses is inversely proportional to RKIP expression levels. We also show that methylation of the RKIP promoter is a major mechanism by which RKIP expression is silenced in CRC. Conclusions: RKIP loss by hypermethylation of its promoter could have a significant influence on colorectal cancer aneuploidy, which might explain its association with metastatic progression.

Dietary intake and bioavailability of trace elements.

In order to assess the nutritional importance of trace elements, it is relevant to consider the factors regulating their metabolism. One of the most important factors is the true intake level. Conventional techniques such as diet history and interview studies in conjunction with standard food tables do not provide the true intake levels from prepared meals. Employing the duplicate portion technique, we have investigated the dietary intake of trace elements in prepared meals consumed by children, adults, and elderly in Sweden. The results indicate that the intake of potassium, magnesium, zinc, copper, and selenium is low when compared with the present recommended dietary allowance (RDA) values. It appears that a marginal deficiency of a number of trace elements may exist in the general population of affluent countries. When the dietary intakes are known, it is necessary to consider the bioavailability. This depends on the chemical form as well as the concentration of other dietary constituents such as fiber, phytate, carbohydrates, macrominerals, and vitamins in the diet. Knowledge of these interactions are important to improve the overall nutritional status of the population in general and patients in particuler.

Pain during Mammography: Impact of Breast Pathologies and Demographic Factors

Objectives: The aim of this study was to systematically assess the pain experienced by patients undergoing mammography for various clinical presentations. Subjects and Methods: Two hundred and twenty-five patients aged 25–85 years (45.43 ± 8.25 years) presenting for mammography were included in the study. Presenting symptoms and clinical diagnosis were provided by the referring physicians and demographic information was obtained from self-reported questionnaires. Mammography results were recorded by the radiologist. Two different but reliable and valid measures of pain – Visual Analog Scale (VAS) and Pain/Discomfort Rating Scale (DRS) – were used to assess pain during mammography and data were statistically analyzed to examine the possible predictors of pain. Results: Forty-nine percent of the patients reported pain during mammography when cut-off level of VAS score was 40; however, when the cut-off level was raised to 60 (considering the preexisting pain as presenting symptom in some patients) only 23% reported pain. With DRS, 7% reported pain, 27% discomfort and 66% neither pain nor discomfort. Biserial correlation between the VAS and DRS scores suggested strong positive agreement between the two measures of pain (r = 0.56, d.f. = 90, p < 0.01). Patients presenting with coexisting breast lumps and preexisting breast pain and those diagnosed with inflammatory conditions of the breast and fibrocystic changes experienced more pain during mammography. Conclusion: Preexisting breast pathologies and demographic factors such as age and educational level of the patient were important in reporting pain during mammography. This finding indicates that proper assessment of pain using standard measures and its association with breast pathologies and demographic factors is important for planning pain management in women undergoing mammography.

Plasma concentrations of alpha-tocopherol and urate in patients with different types of cancer

Objective: To measure plasma concentrations of alpha‐tocopherol and urate to determine whether there is any relationship with different types of cancer before treatment.

Serum Values of Copper, Zinc and Selenium in Adults Resident in Kuwait

Objective: The populations of Kuwait and other Arabian Gulf States are very heterogeneous. Expatriates with different dietary habits constitute approximately 60% of the Kuwaiti population. The aim of this study was to establish a reference range of trace element levels in the serum of the normal population in Kuwait. Method: A total of 379 healthy males (n = 262) and females (n = 117) of various nationalities living in the State of Kuwait were studied. The serum concentrations of zinc (Zn), copper (Cu) and selenium (Se) were measured and the copper/zinc (Cu/Zn) ratio was calculated. Results: The study established the serum Zn, Cu and Se levels in the studied population. The results showed that there was no significant difference in the serum levels of these elements among the different nationalities tested. A significantly higher serum Cu level and Cu/Zn ratio were seen in females. Conclusion: These findings can form the basis and reference for any future studies on trace elements in different pathologic conditions in the Arabian Gulf region.

Primary Omental Torsion: Two Case Reports

Objective: To describe two cases of primary omental torsion as an uncommon cause of abdominal pain. Clinical Presentation and Intervention: Two female patients presented to our surgical service with right-sided abdominal pain. In view of their clinical presentation and workup, both patients required operative intervention. At laparotomy, the cause of the pain was recognized to be due to infarcted omentum secondary to torsion. Both patients underwent omentectomy and appendectomy and had an uneventful recovery. Conclusion: Primary torsion of the omentum is difficult to diagnose preoperatively; this condition is usually detected during surgical exploration for acute abdominal pain.

Postcricoid Carcinoma: Results after Visceral Transposition and Pattern of Recurrence in 27 Patients

Twenty-seven patients with postcricoid carcinoma treated by resection and visceral transposition of the stomach (24), colon (2) or jejunum (1) were studied at Kuwait Cancer Control Centre. Their age a

Expression of estrogen receptor alpha and estrogen receptor beta in fine needle aspirates of breast carcinoma.

OBJECTIVE To evaluate the expression of estrogen receptor beta (ERbeta) in fine needle aspirates (FNAs) and correlate the findings with its expression in tissue sections. STUDY DESIGN In 38 cases of breast carcinoma, expression of estrogen receptor alpha (ERalpha) and ERbeta in aspirates and tissue sections was correlated with the cytologic and histologic grade of the tumor. RESULTS ERalpha and ERbeta were expressed as nuclear staining in 80% and 90% of the cases in tissue sections and 47% and 45% of the cases in aspirates, respectively. Tissue expression of ERalpha (grade 1, 81%; grade 2, 100%) and ERbeta (grade 1, 94%; grade 2, 100%) was greater than in grade 3 tumors (ERalpha, 50%; ERbeta, 70%). In FNAs they were equally distributed in the different cytologic grades. In aspirates 30% of ERalpha negative tumors were positive for ERbeta, while in tissues 75% of ERalpha-negative tumors were positive for ERbeta (p = 0.007). CONCLUSION Demonstration of ERbeta on FNA smears is feasible. It helps identify the specific subcohort of ERbeta-positive tumors in ERalpha-negative breast cancers; that may have therapeutic importance.