Taoufik Nedjadi

Tackling dengue fever: Current status and challenges

According to recent statistics, 96 million apparent dengue infections were estimated worldwide in 2010. This figure is by far greater than the WHO prediction which indicates the rapid spread of this disease posing a growing threat to the economy and a major challenge to clinicians and health care services across the globe particularly in the affected areas.This article aims at bringing to light the current epidemiological and clinical status of the dengue fever. The relationship between genetic mutations, single nucleotide polymorphism (SNP) and the pathophysiology of disease progression will be put into perspective. It will also highlight the recent advances in dengue vaccine development.Thus far, a significant progress has been made in unraveling the risk factors and understanding the molecular pathogenesis associated with the disease. However, further insights in molecular features of the disease and the development of animal models will enormously help improving the therapeutic interventions and potentially contribute to finding new preventive measures for population at risk.

Blocking of cytokines signalling attenuates evoked and spontaneous neuropathic pain behaviours in the paclitaxel rat model of chemotherapy-induced neuropathy

Chemotherapy‐induced peripheral neuropathic pain (CIPNP) is a serious dose‐limiting neurotoxic effect of cancer drug treatment. The underlying mechanism(s) of this debilitating condition, which lacks effective drug treatment, is incompletely understood. However, neural–immune interactions, involving increased expression and release of cytokines, are believed to be involved. Here, we examined, in the paclitaxel rat model of CIPNP, whether plasma levels of 24 cytokines/chemokines change after paclitaxel treatment, and whether blocking of signalling of some of those cytokines would reverse/attenuate behavioural signs of CIPNP.

Association between GSTP1 Genotypes and Hormone Receptor Phenotype in Invasive Ductal Carcinomas of Breast

Eighty six cases of invasive ductal breast carcinomas were utilized to investigate GSTP1 polymorphisms in certain immunohistochemistry (IHC) subtypes of breast cancer with respect to ER, PR and HER2 expression. The frequency of wild allele homozygote, heterozygote and variant allele homozygote genotypes were 46.5%, 52.3% and 1.16% respectively; Whereas 54.3% of the control subjects were GSTP1 wild type allele homozygous, 40.0% were heterozygous and 5.71% mutant allele homozygous. There was dramatic inverted relation between positive IHC ER staining and increasing grade of tumors in general (100%, 88.6%, 40.4%) and especially among tumors with heterozygote genotype of GSTP1 (70%, 35.4%, 22.7). There was increase in positive IHC HER2 staining consistent with higher grades in general (20%, 29.6%, 50.0%), especially among tumors with GSTP1 wild allele homozygote genotype (5.0%, 9.1%, 31.8%). A remarkable reverse relation was also observed between the fraction of IHC hormone receptor phenotype ER+/PR+/ HER2- and increased grade of tumors (60.0%, 45.5%, and 27.3%) especially among tumors with GSTP1 heterozygote genotype, and a similar link was noted regarding ER+/PR-/ HER2- and tumor grade. There was increase in frequency of ER-/PR-/ HER2- (0.0%, 6.8%, and 18.2%) and ER-/PR-/ HER2+ (0.0%, 4.54%, and 40.9%) consistent with the higher grades of tumors in general and especially GSTP1 heterozygote genotype tumors. As a conclusion, there is no correlation between GSTP1 polymorphism and increased risk of breast cancer i.e. the mutant allele is randomly distributed in cancer and control cases. However, there is a link between GSTP1 genotypes and hormone receptor expression status and certain phenotypes of breast cancer, which may have clinical importance.

Genomic Linkage Between Alzheimer's Disease and Type 2 Diabetes

Alzheimers disease (AD) is a major health concern that affects nearly every society worldwide. The disease is an irreversible, progressive and age-related neurodegenerative disorder. It is characterized by impaired cognitive function and the diffuse deposition of amyloid plaques and neurofibrillary tangles. The causes of AD and the underlying mechanisms that trigger the onset of the disease are still a matter of debate. Several epidemiological studies have shown that the development of AD is associated with type 2 diabetes mellitus (T2D). In this review, we provide evidence for the link between T2D and AD, highlighting the critical role of insulin in the pathogenesis of these diseases, and we provide information on the genes that might be involved in the interplay between these two disorders. New insight into the complex biology of AD is necessary for the early diagnosis of the disease, the development of novel drug therapies and the prevention of these health issues.

Trans-cellular transport of short chain fatty acids in the large intestine

Short chain fatty acids (SCFA) are the main end-products of anaerobic degradation of dietary fiber in the colon [1]. SCFA contribute immensely to the body’s energy requirement and regulate numerous cellular processes during both health and disease [2]. SCFA especially butyrate possess anti-cancer activity through induction of apoptosis and promotion of differentiation by modulating the transcription of a number of underlying genes [3]. The exact transport mechanism of SCFA remains ambiguously defined, Hence we aim here to characterize the mechanism of butyrate transport across both luminal and basolateral membranes of the colonic epithelial cells.

Sonic Hedgehog Expression is Associated with Lymph Node Invasion in Urothelial Bladder Cancer

Bladder cancer (BC) is a deadly disease characterized by high recurrence rates and frequent progression to an aggressive phenotype. Dysregulation of various signaling pathways have been implicated in BC tumorigenesis, however, the clinical relevance of sonic hedgehog pathway (Shh) remains under investigated. The aim of the current study was to analyze the prognostic value of Shh expression in patients with bladder carcinoma. Immunohistochemical expression of Shh was performed using tissue microarray with 128 specimens from bladder cancer patients. Kaplan-meier survival was analysed and correlation between Shh protein expression and patients’ clinicopathological parameters wasexamined using Fisher’s exact test. The immuno-staining results revealed that Shh protein exhibits cytoplasmic localization and is expressed in 49% of the analyzed bladder cancer cohort. Our data indicated that high Shh expression significantly correlated with increased lymph node metastasis (p = 0.02), however no association was reported between Shh expression and other clinicopatholigical parameters. High expression of sonic hedgehog was associated with lymph node invasion which may indicate that Shh might play an important role in progression and metastasis of bladder cancer.

Association of Interleukin-6 and Other Cytokines with Self-Reported Pain in Prostate Cancer Patients Receiving Chemotherapy

Background Pain is a common and dose-limiting side effect of many potentially curative cancer chemotherapeutic agents. This chemotherapy-induced pain (CIP) affects the quality of life of cancer patients and survivors and hampers the optimal clinical management of chemotherapy in cancer patients. The underlying mechanisms remain largely unknown, but changes in levels of cytokines/chemokines may contribute to the pathophysiology of CIP. Objective This retrospective study was aimed at examining whether plasma levels of various cytokines change in prostate cancer patients after chemotherapy treatment and whether such changes (if any) are associated with their pain intensity. Methods Using a Luminex assay, plasma levels of 27 cytokines/chemokines were measured in 78 men: 30 patients with metastatic prostate cancer who received chemotherapy (Docetaxel, 75 mg/m2 intravenously), 29 untreated patients with nonmetastatic prostate cancer, and 19 healthy controls. Subjective pain was assessed in chemotherapy-treated cancer patients using the 11-point numeric rating scale (NRS) pain scores. Results Chemotherapy-treated patients with pain (NRS ≥ 3) exhibited significantly increased levels of the pro-inflammatory cytokines (IL-6, IL-8) and chemokines (Eotaxin, VEGF, and IP-10) compared with untreated cancer patients or with patients without pain (NRS = 0). Of the 27 cytokines examined, only IL-6 was positively correlated with pain intensity in the chemotherapy-treated patients with pain. Conclusions These findings suggest that the cytokines, particularly IL-6, whose levels were elevated in the chemotherapy-treated patients may be involved in the pathophysiology of CIP, and that they might be potential new targets for pain control in cancer patients receiving chemotherapy.

Prognostic significance of fibroblast growth factor 19 (FGF19) expression in breast invasive ductal carcinoma

Materials and methods Archival FFPE tumor samples were analyzed using immunohistochemistry (IHC) for monoclonal antiFGF19 (W12) antibody in 193 patients with BC. IHC analysis was done using the automatic system (BenchMark XT; Ventana Medical Systems, Inc. Tucson, AZ, USA). Patients were diagnosed and treated at the Departments of Pathology, Surgery and Oncology, King Abdulaziz University Hospital, Saudi Arabia and the National Oncology Institute, Sabratha, Libya during years 2000-2008.