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The spread of cancer throughout the body is driven by circulating tumour cells (CTCs)1. These cells detach from the primary tumour and move from the blood stream to a new site of subsequent tumour growth. They also carry information about the primary tumour and have the potential to be valuable biomarkers for disease diagnosis and progression, and for the molecular characterization of certain biological properties of the tumour. However, the limited sensitivity and specificity of current methods to measure and study these cells in patient blood samples prevent the realization of their full clinical potential. The use of microfluidic devices is a promising method for isolating CTCs2, 3; however, the devices are reliant on three-dimensional structures, which limit further characterization and expansion of cells on the chip. Here we demonstrate an effective approach to isolate CTCs from blood samples of pancreatic, breast and lung cancer patients, by using functionalised graphene oxide nanosheets on a patterned gold surface. CTCs were captured with high sensitivity at low concentration of target cells (73% ± 32.4 at 3–5 cells/mL blood).

Aptamers are oligonucleotide sequences with a length of about 25−80 bases which have abilities to bind to specific target molecules that rival those of monoclonal antibodies. They are attracting great attention in diverse clinical translations on account of their various advantages, including prolonged storage life, little batch-to-batch differences, very low immunogenicity, and feasibility of chemical modifications for enhancing stability, prolonging the half-life in serum, and targeted delivery. In this Review, we demonstrate the emerging aptamer discovery technologies in developing advanced techniques for producing aptamers with high performance consistently and efficiently as well as requiring less cost and resources but offering a great chance of success. Further, the diverse modifications of aptamers for therapeutic applications including therapeutic agents, aptamer−drug conjugates, and targeted delivery materials are comprehensively summarized.

The MDM2 oncogene has both p53-dependent and p53-independent activities. We have previously reported that antisense MDM2 inhibitors have significant antitumor activity in multiple human cancer models with various p53 statuses (Zhang, Z., Li, M., Wang, H., Agrawal, S., and Zhang, R. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 11636 -11641). We have also provided evidence that MDM2 has a direct role in the regulation of p21, a cyclin-dependent kinase inhibitor. Here we provide evidence supporting functional interaction between MDM2 and p21 in vitro and in vivo. The inhibition of MDM2 with anti-MDM2 antisense oligonucleotide or Short Interference RNA targeting MDM2 significantly elevated p21 protein levels in PC3 cells (p53 null). In contrast, overexpression of MDM2 diminished the p21 level in the same cells by shortening the p21 half-life, an effect reversed by MDM2 antisense inhibition. MDM2 facilitates p21 degradation independent of ubiquitination and the E3 ligase function of MDM2. Instead, MDM2 promotes p21 degradation by facilitating binding of p21 with the proteasomal C8 subunit. The physical interaction between p21 and MDM2 was demonstrated both in vitro and in vivo with the binding region in amino acids 180 -298 of the MDM2 protein. In summary, we provide evidence supporting a physical interaction between MDM2 and p21. We also demonstrate that, by reducing p21 protein stability via proteasome-mediated degradation, MDM2 functions as a negative regulator of p21, an effect independent of both p53 and ubiquitination. p21WAF1/CIP1 , which belongs to the CIP/KIP1 family of cyclindependent kinase inhibitors, has long been characterized as an inhibitor of cell proliferation, but increasing evidence suggests that it plays a role in cell differentiation, senescence, and modulation of apoptosis (1). The regulation of p21 also may be more complicated than previously thought (3-5). Its transcription can be regulated through p53-dependent (2) and -independent pathways (3); its degradation is also processed by ubiquitin-dependent (4) and -independent (5) pathways via proteasome-mediated mechanisms.The MDM2 1 (mouse double minute 2) oncoprotein is a negative regulator of p53 (6) that functions through blocking its transcriptional activity (7) and promoting its proteasome-mediated degradation (8). However, MDM2 now has been shown to interact with other cellular proteins including p19/14 ARF (9), E2F1 (10), p300 (11), ribosomal L5 protein (12), and p73 (13), suggesting that it has p53-independent activities (6). The Ring finger domain in the C terminus of MDM2, containing the ubiquitin E3 ligase activity, is responsible for p53 ubiquitination and subsequent degradation (14). More recently, this E3 ligase has also been shown to facilitate the proteasome-dependent degradation of the androgen receptor (15).The MDM2 oncoprotein is overexpressed in many human malignancies, and high MDM2 levels are associated with a poor prognosis (6). The MDM2 oncoprotein may also have a role in cancer therapy. We have recently developed specifi...

have been presented. [5][6][7] For many years SERS substrates were primarily restricted to noble metal (Au, Ag, and Cu) structures. Recently, it has been found that various semiconductors, such as ZnO, [8] ZnS, [9] TiO 2 , [10] Cu 2 O, [11] and CuO, [12] can also generate weak SERS activity with typical prominent enhancement factors ranging from 10 1 to 10 3 . Therefore, composites or heterostructures between semiconductors (Si, ZnO, and TiO 2 ) and noble metals (Au and Ag) have attracted attention, as a much higher SERS effect could be achieved due to the contributions from both the electromagnetic enhancement (excited by the localized surface plasmon resonance of noble metals) and the semiconductor supporting chemical enhancement (caused by the charge transfer between the noble metal and the adjacent semiconductor). [13][14][15][16][17][18][19][20] ZnO, a versatile semiconductor material with a direct band gap of 3.37 eV, has received special attention due to its excellent performance in supporting chemical enhancement of SERS substrates. [21,22] Several methods have thus been developed to fabricate this new type of ZnO/noble metal hybrid SERS substrate. For example, electroless plating was employed to assemble Ag nanoparticles (Ag-NPs) onto the surface of ZnO nanorods (ZnO-NRs) by sensitizing and activating with Sn 2+ or by irradiation with UV light. [22,23] Interestingly, the Ag-NPs could also be located on the tips of the ZnO-NRs via a photodeposition method or galvanic reduction. [24,25] Alternatively, with the help of surface modification with amino or mercapto groups, Au-NP/ZnO-particle and Au-or Ag-NPs/ZnO-multipods hybrid structures were achieved. [21,26] However, the spatial gaps between these small noble metal particles on the ZnO supporter were too large to work efficiently as SERS "hot spots" and, moreover, the complicated coupling agents for linking the metal NPs onto the ZnO surface, such as (3-aminopropyl) triethoxysilane, may bring extra interferential bands in the SERS measurements, especially if the target analytes have similar Raman spectral response with the coupling agents. To tackle this problem, physical sputtering was exploited. For example, a SERS substrate called "3D hybrid Ag-nanocluster-decorated ZnO nanowire arrays" was fabricated Arrays of Cone-Shaped ZnO Nanorods Decorated with Ag Nanoparticles as 3D Surface-Enhanced Raman Scattering Substrates for Rapid Detection of Trace Polychlorinated BiphenylsA new, highly sensitive and uniform three-dimensional (3D) hybrid surfaceenhanced Raman scattering (SERS) substrate has been achieved via simultaneously assembling small Ag nanoparticles (Ag-NPs) and large Ag spheres onto the side surface and the top ends of large-scale vertically aligned coneshaped ZnO nanorods (ZnO-NRs), respectively. This 3D hybrid substrate manifests high SERS sensitivity to rhodamine and a detection limit as low as 10 −11 m to polychlorinated biphenyl (PCB) 77-a kind of persistent organic pollutants as global environmental hazard. Three kinds of inter-Ag-NP gaps in ...