Hala F. M. Kamel

Resistin, Visfatin, Adiponectin, and Leptin: Risk of Breast Cancer in Pre- and Postmenopausal Saudi Females and Their Possible Diagnostic and Predictive Implications as Novel Biomarkers

The mechanisms of obesity-induced breast carcinogenesis are not clear. One hypothesis is that high levels of adipokines could promote breast cancer (BC) development. The aim of this study was to investigate the correlation of resistin, visfatin, adiponectin, and leptin with BC risk in pre- and postmenopausal females. A total of 82 BC newly diagnosed and histologically confirmed patients and 68 age and BMI matched healthy controls were enrolled. Both groups were subdivided into post- and premenopausal subgroups. Resistin, visfatin, adiponectin, and leptin were measured by ELISA. There were significantly higher levels of leptin, resistin, and visfatin in postmenopausal BC patients than their respective controls. Only in postmenopausal subgroups, leptin, resistin, and visfatin levels were positively correlated with TNM staging, tumor size, lymph node (LN) metastasis, and histological grading. In postmenopausal females, multivariate logistic regression analysis revealed that adiponectin, leptin, visfatin, and resistin were risk factors for BC. Our results suggested that serum resistin, leptin, adiponectin, and visfatin levels as risk factors for postmenopausal BC may provide a potential link with clinicopathological features and are promising to be novel biomarkers for postmenopausal BC.

Evaluation of diagnostic and predictive value of serum adipokines: Leptin, resistin and visfatin in postmenopausal breast cancer.

Obesity is a well-known risk factor for cancer. The associations of obesity with postmenopausal breast cancer (PBC) have been previously proven in clinical studies. The mechanisms underlying these associations remain unexplained completely, however, adipose tissue as an endocrine organ producing adipokines may interfere with cancer development. The aim of this study is to investigate the diagnostic and predictive value of serum levels of leptin, resistin and visfatin with inflammatory and tumour markers in relation to anthropometrics, clinicopathological features of PBC. This study included 298 postmenopausal Saudi females categorised into three groups. One hundred and ten BC patients with age matched, 89 healthy control (HC) and 99 females with benign breast lesion (BBL). For all subjects CA15-3, hsCRP, resistin, visfatin and leptin were measured by ELISA. Serum levels of leptin, resistin and visfatin were significantly higher in BC compared to BBL and HC groups (p<0.05). Their levels were also significantly higher in advanced TNM stage, tumour size, LN invasion, histological grade and negative ER or PR cases. The most significant predictor of leptin level was ER (p<0.05). While for resistin and visfatin level the most significant independent predictor was LN invasion. ROC analysis for serum leptin revealed AUC=0.795; 95% CI, 0.724-0.866. Resistin showed AUC=0.875; 95% CI, 0.821-0.928. Meanwhile, visfatin greater than 12.2ng/mL demonstrated a sensitivity and specificity of 97.6% and 92.6%, respectively and AUC=0.724; 95% CI, 0.643-0.804. In conclusion serum leptin, resistin, and visfatin levels could be considered of potential diagnostic value for PBC and they would be independent predictors of LN invasion and ER negative PBC cases.

Exploitation of Gene Expression and Cancer Biomarkers in Paving the Path to Era of Personalized Medicine

Cancer therapy agents have been used extensively as cytotoxic drugs against tissue or organ of a specific type of cancer. With the better understanding of molecular mechanisms underlying carcinogenesis and cellular events during cancer progression and metastasis, it is now possible to use targeted therapy for these molecular events. Targeted therapy is able to identify cancer patients with dissimilar genetic defects at cellular level for the same cancer type and consequently requires individualized approach for treatment. Cancer therapy begins to shift steadily from the traditional approach of “one regimen for all patients” to a more individualized approach, through which each patient will be treated specifically according to their specific genetic defects. Personalized medicine accordingly requires identification of indicators or markers that guide in the decision making of such therapy to the chosen patients for more effective therapy. Cancer biomarkers are frequently used in clinical practice for diagnosis and prognosis, as well as identification of responsive patients and prediction of treatment response of cancer patient. The rapid breakthrough and development of microarray and sequencing technologies is probably the main tool for paving the way toward “individualized biomarker-driven cancer therapy” or “personalized medicine”. In this review, we aim to provide an updated knowledge and overview of the current landscape of cancer biomarkers and their role in personalized medicine, emphasizing the impact of genomics on the implementation of new potential targeted therapies and development of novel cancer biomarkers in improving the outcome of cancer therapy.

Critical Appraisal of Advanced Glycation End Products (AGEs) and Circulating Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictive Biomarkers for Cardiovascular Disease in Hemodialysis Patients

The interaction of advanced glycation end products (AGE) and their receptors promote vascular complications of diabetes in hemodialysis (HD) patients. The soluble form of the receptor for the advanced glycation end-products (sRAGE) has been studied as a vascular biomarker in various diseases with controversial results. Our aim was to evaluate the association of the serum levels of the AGEs and their receptor sRAGE with cardiovascular disease (CVD) and the cardiovascular risk factors among HD patients. There were 130 HD patients and 80 age and gender matched control subjects were involved; 31.5% of the HD group were diabetic, which was an underlying cause of renal impairment; 36.1% had CVD, which was comprising 44.7% of diabetics and 55.3% of non-diabetic patients. The AGEs and sRAGE were assessed by enzyme linked immunosorbent assay (ELISA). In addition, the lipid profile, glycemic indices, pre-dialysis renal function tests, and hemoglobin % (Hb) were evaluated. The results show that the circulating AGEs and sRAGE levels were significantly higher in the HD patients. Those with underlying diabetes displayed higher sRAGE levels, which were positively correlated with hyperglycemia, HbA1C, and total cholesterol (TC). The HD patients with an increased serum sRAGE exhibited more cardiovascular risk factors (hypercholesterolemia and anemia) with a high prevalence of CVD. Using a linear regression analysis, we found a significant association of sRAGE with CVD and TC among HD patients, regardless of whether associating diabetes was an underlying cause of renal impairment. Overall, the HD patients displayed significantly higher serum AGEs with a concomitant increase in the circulating sRAGE levels, mainly in the diabetic HD, which were significantly associated with the CVD (independent predictors) and CV risk factors (hypercholesterolemia), mainly sRAGEs, regardless of the underlying diabetes mellitus. This highlights the prognostic role of AGEs and sRAGE in HD patients regardless of underlying cause in order to predict the risk for CVD.

Potential Cardiovascular and Renal Protective Effects of Vitamin D and Coenzyme Q10 in l-NAME-Induced Hypertensive Rats☆

Background Hypertension is one of the primary modifiable risk factors for cardiovascular disease. Adequate vitamin D (vit D) levels have been shown to reduce vascular smooth muscle contraction and to increase arterial compliance, which may be beneficial in hypertension. Further, coenzyme Q10 (COQ10) through its action to lower oxidative stress has been reported to have beneficial effects on hypertension and heart failure. This study examined the possible cardiac and renal protective effects of vit D and COQ10 both separately and in combination with an angiotensin II receptor blocker, valsartan (vals) in l‐NAME hypertensive rats. Materials and Methods Hypertension was induced in rats by l‐NAME administration. Following induction of hypertension, the rats were assigned into the following 6 subgroups: an l‐NAME alone group and treated groups receiving the following drugs intraperitoneally for 6 weeks; vals, vit D, COQ10 and combination of vals with either vit D or COQ10. A group of normotensive rats were used as negative controls. At the end of the treatment period, blood pressure, serum creatinine, blood urea nitrogen, lipids and serum, cardiac and renal parameters of oxidative stress were measured. Results Compared to the l‐NAME only group, all treatments lowered systolic, diastolic, mean arterial pressure, total cholesterol, low‐density lipoprotein cholesterol, and creatinine levels as well as TNF‐&agr; and malondialdehyde. Further, the agents increased serum, cardiac and renal total antioxidant capacity. Interestingly, the combination of agents had further effects on all the parameters compared to treatment with each single agent. Conclusions The study suggests that the additive protective effects of vit D and COQ10 when used alone or concurrent with vals treatment in hypertensive rats may be due to their effects as antioxidants, anticytokines and blood pressure conservers.

Correction to: Assessment of tumor necrosis factor alpha polymorphism TNF-α−238 (rs 361525) as a risk factor for development of acute kidney injury in critically ill patients

Critically ill patients revealed significant adverse outcomes (sepsis, septic shock, organ dysfunction/failure, and mortality) despite variable effort. Aim: this study evaluated the association of TNF-a−238 (rs 361525) with adverse outcomes in critically ill patients. TNF-α−238 (rs 361525) SNP was performed by RT-PCR on 200 critically-ill patients (112 had severe sepsis and septic shock and 88 were septic), 127 of them had AKI. Urinary N-acetyl-β-(d)-glucosaminidase and serum creatinine were assessed by modified Jaffé and ELISA respectively. These results revealed that heterozygous genotype GA of TNF-α−238 (rs 361525) SNP significantly increased the risk of adverse-outcome (mortality rate) (P = 0.0001; OR 8.9), regardless of organ dysfunction (P = 0.09) or severity of sepsis (P = 0.6). Moreover, heterozygous genotype GA of TNF-α−238 (rs 361525) SNP was significantly associated with inflammatory marker (sTNF-α) (P = 0.014) and tubular injury marker (uNAG) (P = 0.001) that displayed a significant association with severity of sepsis (0.001, 0.035) and organ dysfunction (0.012, 0.0001) respectively. In critically ill patients with sepsis induced AKI, serum TNF-α and uNAG measured at admission can predict severity of sepsis and AKI (defined by REFILE) occurrence along with pre-existing CKD and DM. However, TNF−238 yielded additional prognostic information on ICU mortality irrelevant to AKI in septic patients.

Wild-Type Isocitrate Dehydrogenase 1 Over-Expression is Related to Cancer Stem Cells Survival in Lung Adenocarcinoma

ABSTRACT Altered metabolism is one of the characteristics of cancer cells. We evaluated the expression of wild-type Isocitrate Dehydrogenase 1 (IDH1) and the cancer stem cells (CSCs) marker CD44 by real-time PCR and levels of reduced form of glutathione in lung biopsies of 32 adenocarcinoma patients and 18 control subjects. We found that IDH1 and CD44 expression and the levels of reduced form of glutathione were significantly higher in lung adenocarcinoma patients. IDH1 was positively correlated with CD44 and reduced form of glutathione. In conclusion, wild-type IDH1 is over-expressed in lung adenocarcinoma which probably promoted tumor progression via increasing CSCs survival.

Molecular Fingerprints and Biomarkers of Breast Cancer

Substantial progress has been made over the past three decades in understanding breast cancer (BC) molecular biology, genomics, and targeted therapy. The recent comprehensive molecular and pathological diversity observed in BC patients indicates that BC is not a homogeneous disease; It may be appropriately defined as a myriad of diseases. The explosion of molecular information in the past 10 years has led to a better understanding of the biologic diversity of breast cancers (BCs), and clues to the different etiologic pathways to BC development. It will be useful to study the epigenetics of BC cells and define the mechanisms of both genetic and epigenetic driving alterations beside the mutations. Identifying the oncogenes and tumor suppressor genes is the purpose cancer diagnostics and therapeutics. Oncogenes as well as novel ones involved in the significantly altered regions would enable researchers to identify new causes and molecular pathways that may be targeted at BC treatment. Our main goal is to provide comprehensive understanding of underlying molecular mechanisms and hallmarks of BC, focusing on the identification of fingerprints and novel molecular targets that will greatly improve the cancer predictive, prognostic, and diagnostic biomarkers and, in addition, the possible targets for novel therapies.