Biotargeted nanomedicines for cancer: six tenets before you begin

Biotargeted nanomedicines have captured the attention of academic and industrial scientists who have been motivated by the theoretical possibilities of the ‘magic bullet’ that was first conceptualized by Paul Ehrlich at the beginning of the 20th century. The Biotargeting Working Group, consisting of more than 50 pharmaceutical scientists, engineers, biologists and clinicians, has been formed as part of the National Cancer Institute’s Alliance for Nanotechnology in Cancer to harness collective wisdom in order to tackle conceptual and practical challenges in developing biotargeted nanomedicines for cancer. In modern science and medicine, it is impossible for any individual to be an expert in every aspect of biology, chemistry, materials science, pharmaceutics, toxicology, chemical engineering, imaging, physiology, oncology and regulatory affairs. Drawing on the expertise of leaders from each of these disciplines, this commentary highlights six tenets of biotargeted cancer nanomedicines in order to enable the translation of basic science into clinical practice

Microfluidics: reframing biological enquiry

The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science

Length-weight relationships of fishes captured from Izmir Bay, Central Aegean Sea

WOS: 000250762200012Weight-length relationships are presented for 60 fish species captured from Izmir Bay, Central Aegean Sea. Samples were collected using bottom trawls (mesh sizes 24 mm at stretched cod-end). The b values W = aL(b) showed a mean value of 3.027 (SE = +/- 0.03) and more than 50% of the values ranged between 2.912 and 3.189. One species, Cepola macrophthalma, showed strong negative allometric growth

Major Depresif Bozukluğu Olan Türk Hastalarda 5-HTTLPR Polimorfizmin ve Sitalopram Yanıtı Arasındaki İlişkisi

The objective of this study was to investigate the relationship between the genetic polymorphism of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the response to citalopram treatment and side effects in Turkish patients with major depressive disorder. The study involved 51 patients who received 10-40 mg/day of citalopram for 4 to 6 weeks. Clinical symptoms were evaluated by the 17-item Hamilton Depression Rating (HAMD-17) scale, Clinical Global Impression (CGI) and UKU side effect rating scale (UKU) at weeks 4 and/or 6. The 5-HTTLPRL/S polymorphism was determined by slowdown-polymerase chain reaction method. Of the fifty-one patients, 13 (26%) were the LL genotype, 21 (41%) were the LS genotype, 17 (33%) were the SS genotype. L allele seems to be associated with better response due to odds ratio for L allele versus S allele despite statistically insignificant. In terms of CGI-Severity scale, The LL genotype versus the LS genotype had a higher risk at the week 6 (P<0.05). On the other hand, apart from this comparison, there is no significant difference in CGI-Severity and Improvement and UKU scales according to the distribution of genotypes at week 4 and/or 6. However, these findings surely need further investigation and confirmation. © 2016, Turkish Pharmacists Association. All rights reserved

STAT3 is a substrate of SYK tyrosine kinase in B-lineage leukemia/lymphoma cells exposed to oxidative stress

We provide unprecedented genetic and biochemical evidence that the antiapoptotic transcription factor STAT3 serves as a substrate for SYK tyrosine kinase both in vitro and in vivo. Induction of SYK in an ecdysone-inducible mammalian expression system results in STAT3 activation, as documented by tyrosine phosphorylation and nuclear translocation of STAT3, as well as amplified expression of several STAT3 target genes. STAT3 activation after oxidative stress (OS) is strongly diminished in DT40 chicken B-lineage lymphoma cells rendered SYK-deficient by targeted disruption of the syk gene. Introduction of a wild-type, C-terminal or N-terminal SH2 domain-mutated, but not a kinase domain-mutated, syk gene into SYK-deficient DT40 cells restores OS-induced enhancement of STAT-3 activity. Thus, SYK plays an important and indispensable role in OS-induced STAT3 activation and its catalytic SH1 domain is critical for this previously unknown regulatory function. These results provide evidence for the existence of a novel mode of cytokine-independent cross-talk that operates between SYK and STAT3 pathways and regulates apoptosis during OS. We further provide experimental evidence that SYK is capable of associating with and phosphorylating STAT3 in human B-lineage leukemia/lymphoma cells challenged with OS. In agreement with a prerequisite role of SYK in OS-induced STAT3 activation, OS does not induce tyrosine phosphorylation of STAT3 in SYK-deficient human proB leukemia cells. Notably, inhibition of SYK with a small molecule drug candidate prevents OS-induced activation of STAT3 and overcomes the resistance of human B-lineage leukemia/lymphoma cells to OS-induced apoptosis

The impact of CYP2C19 polymorphisms on citalopram metabolism in patients with major depressive disorder

Suzen, Sinan/0000-0003-1779-5850; OZEL-KIZIL, ERGUVAN TUGBA/0000-0001-9657-1382; ozguven, halise/0000-0002-9355-2757WOS: 000368268000010PubMed: 26343256What is known and objective: Genetic variations in drug-metabolizing enzyme genes change drug pharmacokinetics and response. CYP2C19 is a clinically important enzyme that metabolizes citalopram (CIT). The objective of this study was to determine CYP2C19 genetic polymorphisms and to evaluate the impact of these polymorphisms on the metabolism of citalopram in a sample of the Turkish population. We also assessed *17 polymorphism in healthy subjects in this population. Methods: The CYP2C19 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method (209 healthy individuals and 50 patients for CIT metabolism), and the plasma concentrations of CIT and demethylcitalopram (DCIT) were quantified by high-performance liquid chromatography. Results and discussion: The CYP2C19*1 and *17 allele frequencies for the patient group and the healthy group were 71.0%, 18.0% and 81.1%, 18.9%, respectively. There was no significant difference between the two groups (P > 0 . 05). The mean plasma concentrations and the mean dose-corrected (C/D) plasma levels of DCIT were significantly higher in patients with the CYP2C19*1/*1 genotype compared to patients with CYP2C19*1/*2 and CYP2C19*2/*2 genotypes (P 0 . 05). What is new and conclusion: Our data suggest that CYP2C19*17 polymorphism does not have a significant effect on CIT metabolism. In contrast CYP2C19*2 polymorphism has a prominent role and is likely to contribute to interindividual variability in CIT metabolism in vivo at therapeutic doses.Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S147]This work was supported by The Scientific and Technological Research Council of Turkey under Project 109S147