Clinical Implications of Adiponectin and Inflammatory Biomarkers in Type 2 Diabetes Mellitus

Objectives: To study the interrelationships of adiponectin, C-reactive protein (CRP) and fibrinogen with each other in T2DM patients with (T2DM-C) and without complications (T2DM-NC) among healthy individuals. Design and methods: The study comprised of 120 T2DM-C, 59 T2DM-NC patients and 40 healthy volunteers. Biochemical markers were determined in the serum. Results: Positivity rates of CRP and fibrinogen were significantly increased in T2DM-C as compared to T2DM-NC or controls, whereas adiponectin showed highest level in healthy individuals. Inflammatory biomarkers were inversely correlated with adiponectin (P < 0.01). Lipid profiles, kidney functions and BMI, showed positive significant correlation with CRP and fibrinogen but negative correlation with adiponectin. For better detection of T2DM, the combined sensitivity (98.9%) and specificity (92.5%) of fibrinogen and adiponectin was higher than the combined sensitivity and specificity of fibrinogen and CRP or adiponectin and CRP or than that of the biomarkers alone. Conclusion: Elevated levels of CRP and fibrinogen and reduced level of adiponectin can be used for early diagnosis of T2DM and can predict diabetic complications.     

Comparison of cytokeratin 20 RNA and angiogenin in voided urine samples as diagnostic tools for bladder carcinoma

BACKGROUND: We evaluated the diagnostic efficacy of urinary angiogenin (ANG) and cytokeratin 20 (CK-20) mRNA in comparison with voided urine cytology in the detection of bladder cancer patients. OBJECTIVES AND METHODS: A total of 97 Egyptian patients provided a single voided urine sample for ANG, CK-20 and cytology before cystoscopy. Of the 97 cases, 63 were histologically diagnosed as bladder cancer; 33 with transitional cell carcinoma (TCC) and 30 with squamous cell carcinoma (SCC), whereas the remaining 34 had benign urological disorders. A group of 46 healthy volunteers were also included in this study. Voided urine was centrifuged and the supernatant was used for estimation of ANG by EIA and confirmed by Western blotting (WB). The urine sediment was used for cytology and RNA extraction. CK-20 RNA was detected by RT-PCR. RESULTS: The best cutoff value for ANG was calculated by a ROC curve as 322.7 ng/mg protein. The median urinary ANG level in bladder carcinoma, benign urological disorders and healthy volunteer groups was: 802.7, 425 and 33 pg/mg protein, respectively. The positivity rate for urinary CK-20 mRNA of the control, benign and malignant groups was 0%, 2.9% and 82.3%, respectively (P = 0.000); while the rates for ANG were 11.6%, 54.8% and 75.4%, respectively (P = 0.000). There was no significant difference in positivity rates of CK-20 and ANG with respect to sex, smoking, schistosomiasis, urine cytology, tumor grade, tumor stage, hematuria or pus cells. The overall sensitivity and specificity were 71.4% and 90% for voided urine cytology, 75.4% and 70.3% for ANG, and 82.3% and 98.8% for CK-20. Combined sensitivity of voided urine cytology with ANG and CK-20 together (98.2%) was higher than either the combined sensitivity of voided urine cytology with ANG (96.5%) or with CK-20 (91.6%) or than that of the biomarker alone. We demonstrated significant positive correlation between CK-20 positivity with age (P = 0.043) and nodal involvement (P = 0.037); however, there was no significant correlation between CK-20 and ANG with the other clinicopathological parameters. CONCLUSIONS: Our data indicate that CK-20 and ANG in voided urine had higher sensitivities compared to voided urine cytology. However, when specificity was considered, CK-20 alone had superior sensitivity and specificity compared to ANG and voided urine cytology.     

Prognostic value of cell-cycle regulators and cellular biomarkers in laryngeal squamous cell carcinoma

Objective

Combining information derived from cellular biomarkers as telomerase and genes encoding cyclin dependent kinase inhibitors (p16^INK4a and p15^INK4b) is needed to facilitate the stratification of individual patients within the conventional clinicopathologic parameters.

Design and methods

One hundred forty laryngeal squamous cell carcinoma (LSCC) tissue specimens were investigated for telomerase activity and the deletions of p16^INK4a and p15^INK4b genes.

Results

Of the 140 tissues assayed, 71% demonstrated high telomerase activity, 68.6% and 80% showed deletions in p16^INK4a and p15^INK4b genes, respectively. Significant difference was observed between telomerase activity, p16^INK4a and p15^INK4b deletions among each other and with advanced stage, poorly differentiated grades, high proliferation and DNA aneuploidy. The markers and the aforementioned clinicopathological factors were correlated with progression in univariate analysis; and associated with survival in multivariate analysis.

Conclusion

Progression of LSCC is accompanied by a parallel increase in telomerase activity and deletions in cell-cycle regulators (p16^INK4a, p15^INK4b) which may assist in prognostication and better classification of patients for treatment.     

Potential Influence of Interleukin-1 Receptor Antagonist Gene Polymorphism on Knee Osteoarthritis Risk

Objectives: Genes encoding for cytokines have been associated with susceptibility for joint osteoarthritis (OA) and interleukin (IL)-1 gene is supposed to be involved in the cartilage destruction process. In this regard, interleukin-1 receptor antagonist (IL-1RA) competing with IL-1 for binding to its receptor may act as an inhibitor of cartilage breakdown. We assessed the association of primary knee OA with IL-1RA region as a putative factor of susceptibility to knee OA in Egyptian patients. Design and methods: Eighty patients with primary knee OA and 40 aged-matched healthy controls were included into the study. DNA samples were used to study genotypes of IL-1RN gene by polymerase chain reaction (PCR) in both groups. Results: An increased frequency of the IL-1RN*1 and IL-1RN*2 alleles was found in OA patients relative to controls (60.5% vs. 39.5%, P = 0.039, 85.4% vs. 14.6%, P = 0.002, respectively) however, only the carriage rate of IL-1RN*2 allele was found to be significant when OA patients were compared to the controls. Significant higher frequencies of IL-1RN*1/*2 and IL-1RN*2/*2 genotypes in OA patients were observed as compared with controls. Both visual analogue scale (VAS) and radiographic score revealed significant correlation with both the allelic frequency and the carriage rate of IL-1RN*2 allele. Moreover, absolute frequency of IL-1RN*1/*2 genotype OA patients revealed severe VAS and high radiographic score. Conclusion: These results suggest that IL-1RN*2 allele represent a significant factor influencing the severity and course of knee OA; thereby supporting the potential role of IL-1 in the pathogenesis of this disease.     

Assessment of maintenance oral etoposide following induction chemotherapy with gemcitabine and cisplating in chemonaive extensive small cell lung cancer

Objective

The aim of our study was to evaluate the response and tolerability to treatment when using gemcitabine-cisplatin combination (GC), followed by maintenance therapy of oral etoposide for non-progressive patients in trial to improve progression free survival and overall survival.

Methods

Thirty nine patients with extensive small cell lung cancer (SCLC) and ECOG ≤ 2 received 4 cycles of chemotherapy consisting of gemcitabine 1000 mg/m² (day 1 and 8) cisplating 75 mg/m² (day 1) every three weeks. Twenty seven non-progressive patients after 4 cycles of chemotherapy were randomized either to receive oral etoposide 50 mg/m² for consecutive 15 days every 3 weeks vs no therapy for three months or progression.

Results

Thirty nine eligible patients treated with GC, 27 non progressive patients were subsequently randomized to oral etoposide or observation. Median follow-up was 18 months. The overall response rate to GC was 59% and toxicity to oral etoposide was mild. There was improvement in median progression-free survival (PFS) favoring the maintenance arm of 10.5 months vs 7 months (P < 0.05). Median overall survival (OS) had improved towards the maintenance arm (13 vs 11.5 months). One year survival (60% vs 24%), 18 months survival (20% vs 5%) favoring the maintenance. Multivariate analysis revealed that age, performance status, maintenance therapy, and response to treatment were independent prognostic factors for OS. Age, maintenance therapy, and response to treatment were highly significant factors for PFS.

Conclusion

Gemcitabine-cisplatin is an effective and tolerable regiment for extensive disease of SCLC. The addition of 3 months of oral etoposide in non progressing patients was associated with a significant improvement of PFS and longer OS.     

Soluble cytokeratin-19 and E-selectin biomarkers: their relevance for lung cancer detection when tested independently or in combinations

OBJECTIVES: Determination of tumor biomarkers in serum has been proposed as an alternative and noninvasive way of establishing diagnosis for lung cancer. The aim of this study was to assess the combined use of Cyfra 21-1; the soluble fragment of cytokeratin 19, and soluble E-selectin; endothelial adhesion molecule, for improving the accuracy of diagnosing and screening lung cancer. MATERIALS AND METHODS: Serum Cyfra 21-1 and sE-selectin were determined using electrochemiluminescent immunoassay and enzyme linked immunosorbent assay, respectively, in 52 patients with histologically proven lung cancer, 40 patients with benign lung diseases and 50 healthy volunteers. RESULTS: Both markers were significantly increased in lung cancer patients as compared to healthy, for benign lung diseases Cyfra 21-1 perform well than sE-selectin. Sensitivities of Cyfra 21-1 and sE-selectin at 95th percentiles of the normal group were 96.2% and 92.3%, while at 95th percentiles of the benign lung diseases were 57.7% and 5%, respectively. In ROC curves, the diagnostic power for the detection of lung cancer was similar for Cyfra 21-1 and sE-selectin; however, when compared with benign lung diseases, Cyfra 21-1 was superior to sE-selectin. The highest sensitivity (99.8%) was reported when the two markers were combined. CONCLUSION: Cyfra 21-1 and sE-selectin show good performance in detecting lung cancer from normal groups, however, Cyfra 21-1 was superior to sE-selectin in discriminating lung cancer from benign lung diseases.     

Clinical impact of circulating oncogenic MiRNA-221 and MiRNA-222 in glioblastoma multiform

Journal of Neuro-Oncology - Approach selection paradigm for tuberculum sellae meningiomas (TSMs) is still a point of discussion. The trans-eyebrow supraorbital keyhole approach (TSKA) is a...     

Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia

Objectives: Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE). Authors determine the clinical diagnostic role for thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1) as endothelial markers and C-reactive protein (CRP), and interlukin-6 (IL-6) as inflammatory markers when tested independently or in combinations. Materials and methods: We conducted a retrospective study in a cohort of 185 women grouped as 80 women with PE, 55 normotensive pregnant and 50 healthy non-pregnant. Plasma levels of TM, PAI-1, CRP and IL-6 were examined using enzyme linked immunosorbent assays. Results: Median levels and the positivity rates for the investigated markers were higher in PE as compared to the other groups (P < 0.0001). Using linear regression analysis, the investigated markers were significantly correlated regarding healthy nonpregnant vs PE or normotensive pregnant vs PE. The sensitivity of PAI-1 was the highest (98%) among the tested biomarkers. Combination between the investigated markers revealed absolute sensitivity (100%) and reliable specificity especially when PAI-1 was combined with CRP at 83% specificity. Conclusions: Investigated endothelial and inflammatory markers revealed sensitive diagnostic test for PE. However, coupled combination between PAI-1 with CRP showed superior both sensitivity and specificity which represent a promising new approach for detection of PE.