RASSF Signalling and DNA Damage: Monitoring the Integrity of the Genome?

The RASSF family of proteins has been extensively studied in terms of their genetics, structure and function. One of the functions that has been increasingly studied is the role of the RASSF proteins in the DNA damage response. Surprisingly, this research, which encompasses both the classical and N-terminal RASSF proteins, has revealed an involvement of the RASSFs in oncogenic pathways as well as the more familiar tumour suppressor pathways usually associated with the RASSF family members. The most studied protein with respect to DNA damage is RASSF1A, which has been shown, not only to be activated by ATM, a major regulator of the DNA damage response, but also to bind to and activate a number of different pathways which all lead to and feedback from the guardian of the genome, p53. In this review we discuss the latest research linking the RASSF proteins to DNA damage signalling and maintenance of genomic integrity and look at how this knowledge is being utilised in the clinic to enhance the effectiveness of traditional cancer therapies such as radiotherapy

Time-resolved photoluminescence study of CdSe/CdMnS/CdS core/multi-shell nanoplatelets

We used photoluminescence spectroscopy to resolve two emission features in CdSe/CdMnS/CdS and CdSe/CdS core/multi-shell nanoplatelet heterostructures. The photoluminescence from the magnetic sample has a positive circular polarization with a maximum centered at the position of the lower energy feature. The higher energy feature has a corresponding signature in the absorption spectrum; this is not the case for the low-energy feature. We have also studied the temporal evolution of these features using a pulsed-excitation/time-resolved photoluminescence technique to investigate their corresponding recombination channels. A model was used to analyze the temporal dynamics of the photoluminescence which yielded two distinct timescales associated with these recombination channels. The above results indicate that the low-energy feature is associated with recombination of electrons with holes localized at the core/shell interfaces; the high-energy feature, on the other hand, is excitonic in nature with the holes confined within the CdSe cores. © 2016 Author(s)

Magneto-optical studies of CdSe/CdMnS/CdS core/multi-shell colloidal nanoplatelets

We studied the photoluminescence (PL)) from CdSe/CdMnS/CdS core/multi-shell colloidal nanoplatelets, a versatile platform to study the interplay of optical properties and nanomagnetism. The photoluminescence (PL) exhibits σ+ polarization in the applied magnetic field. Our measurement detects the presence of even a single magnetic monolayer shell. The PLL consists of a higher and a lower energy component; the latter exhibits a circular polarization peak. The time-resolved PL (trPL) shows a red shift as function of time delay. At early (later) times the trPL spectra coincide with the high (low) energy PL component. A model is proposed to interpret these results. © 2016 SPIE

Time resolved photoluminescence study of magnetic CdSe/CdMnS/CdS core/multi-shell nanoplatelets

Colloidal semiconductor nanoplatelets (NPLs) are quasi 2D-nanostructures that are grown and processed inexpensively using a solution based method and thus have recently attracted considerable attention. We observe two features in the photoluminescence spectrum, suggesting two possible recombination channels. Their intensity ratio varies with temperature and two distinct temperature regions are identified; a low temperature region (10K < T < 90K) and a high temperature region (90K < T < 200K). This ratio increases with increasing temperature, suggesting that one recombination channel involves holes that are weakly localized with a localization energy of 0.043meV. A possible origin of these localized states are energy-variations in the xy-plane of the nanoplatelet. The presence of positive photoluminescence circular polarization in the magnetically-doped core/multi-shell NPLs indicates a hole-dopant exchange interaction and therefore the incorporated magnetic Manganese ions act as a marker that determines the location of the localized hole states.1 Time-resolved measurements show two distinct timescales (τfast and τslow) that can be modeled using a rate equation model. We identify these timescales as closely related to the corresponding recombination times for the channels. The stronger hole localization of one of these channels leads to a decreased electron-hole wave function overlap and thus a decreased oscillator strength and an increased lifetime. We show that we can model and understand the magnetic interaction of doped 2D-colloidal nanoplatelets which opens a pathway to solution processable spin controllable light sources. Copyright © 2017 SPIE

Testing of SNS-032 in a panel of human neuroblastoma cell lines with acquired resistance to a broad range of drugs

Novel treatment options are needed for the successful therapy of patients with high-risk neuroblastoma. Here, we investigated the cyclindependent kinase (CDK) inhibitor SNS-032 in a panel of 109 neuroblastoma cell lines consisting of 19 parental cell lines and 90 sublines with acquired resistance to 14 different anticancer drugs. Seventy-three percent of the investigated neuroblastoma cell lines and all four investigated primary tumor samples displayed concentrations that reduce cell viability by 50% in the range of the therapeutic plasma levels reported for SNS-032 (<754 nM). Sixty-two percent of the cell lines and two of the primary samples displayed concentrations that reduce cell viability by 90% in this concentration range. SNS-032 also impaired the growth of the multidrug-resistant cisplatin-adapted UKF-NB-3 subline UKF-NB-3rCDDP1000 in mice. ABCB1 expression (but not ABCG2 expression) conferred resistance to SNS-032. The antineuroblastoma effects of SNS-032 did not depend on functional p53. The antineuroblastoma mechanism of SNS-032 included CDK7 and CDK9 inhibition–mediated suppression of RNA synthesis and subsequent depletion of antiapoptotic proteins with a fast turnover rate including X-linked inhibitor of apoptosis (XIAP), myeloid cell leukemia sequence 1 (Mcl-1), baculoviral IAP repeat containing 2 (BIRC2; cIAP-1), and survivin. In conclusion, CDK7 and CDK9 represent promising drug targets and SNS-032 represents a potential treatment option for neuroblastoma including therapy-refractory cases

The Tumor Suppressor Gene, RASSF1A, Is Essential for Protection against Inflammation -Induced Injury

10.1371/journal.pone.0075483PLoS ONE810-POLN