Elevated rates of reactive oxygen species (ROS) have been detected in almost all cancers, where they promote many aspects of tumour development and progression. However, tumour cells also express increased levels of antioxidant proteins to detoxify from ROS, suggesting that a delicate balance of intracellular ROS levels is required for cancer cell function. Further, the radical generated, the location of its generation, as well as the local concentration is important for the cellular functions of ROS in cancer. A challenge for novel therapeutic strategies will be the fine tuning of intracellular ROS signalling to effectively deprive cells from ROS-induced tumour promoting events, towards tipping the balance to ROS-induced apoptotic signalling. Alternatively, therapeutic antioxidants may prevent early events in tumour development, where ROS are important. However, to effectively target cancer cells specific ROS-sensing signalling pathways that mediate the diverse stress-regulated cellular functions need to be identified. This review discusses the generation of ROS within tumour cells, their detoxification, their cellular effects, as well as the major signalling cascades they utilize, but also provides an outlook on their modulation in therapeutics.

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Reactive oxygen species in cancer

Stem cells are defined as cells able to both extensively self-renew and differentiate into progenitors. Research data show that more resistant stem cells than common cancer cells exist in cancer patients.To identify unrecognized differences between cancer stem cells and cancer cells might be able to develope effective classification,diagnose and treat ment for cancer.

Stem Cells,Cancer and Cancer Stem Cells

The text consists of two sections, one for those studying or practicing diagnostic radiology, nuclear medicine and radiation oncology; the other for those engaged in the study or clinical practice of radiation oncology--a new chapter, on radiologic terrorism, is specifically for those in the radiation sciences who would manage exposed individuals in the event of a terrorist event. The 17 chapters in Section I represent a general introduction to radiation biology and a complete, self-contained course especially for residents in diagnostic radiology and nuclear medicine that follows the Syllabus in Radiation Biology of the RSNA. The 11 chapters in Section II address more in-depth topics in radiation oncology, such as cancer biology, retreatment after radiotherapy, chemotherapeutic agents and hyperthermia.

Radiobiology for the Radiologist

The complexity, diversity, and heterogeneity of tumors seriously undermine the therapeutic potential of treatment. Therefore, the current trend in clinical research has gradually shifted from a focus on monotherapy to combination therapy for enhanced treatment efficacy. More importantly, the cooperative enhancement interactions between several types of monotherapy contribute to the naissance of multimodal synergistic therapy, which results in remarkable superadditive (namely “1 + 1 > 2”) effects, stronger than any single therapy or their theoretical combination. In this review, state-of-the-art studies concerning recent advances in nanotechnology-mediated multimodal synergistic therapy will be systematically discussed, with an emphasis on the construction of multifunctional nanomaterials for realizing bimodal and trimodal synergistic therapy as well as the intensive exploration of the underlying synergistic mechanisms for explaining the significant improvements in synergistic therapeutic outcome. Furtherm...

Nanotechnology for Multimodal Synergistic Cancer Therapy

Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery

The design and development of water dispersible, pH responsive peptide mimic shell cross-linked magnetic nanocarriers (PMNCs) using a facile soft-chemical approach is reported. These nanocarriers have an average size about 10 nm, are resistant to protein adsorption in physiological medium, and transform from a negatively charged to a positively charged form in the acidic environment. The terminal amino acid on the shell of the magnetic nanocarriers allows us to create functionalized exteriors with high densities of organic moieties (both amine and carboxyl) for conjugation of drug molecules. The drug-loading efficiency of the nanocarriers is investigated using doxorubicin hydrochloride (DOX) as a model drug to evaluate their potential as a carrier system. Results show high loading affinity of nanocarriers for anticancer drug, their sustained release profile, magnetic-field-induced heating, and substantial cellular internalization. Moreover, the enhanced toxicity to tumor cells by DOX-loaded PMNCs (DOX-PMNCs) under an AC magntic field suggest their potential for combination therapy involving hyperthermia and chemotherapy.

pH-Responsive Peptide Mimic Shell Cross-Linked Magnetic Nanocarriers for Combination Therapy

The translationally controlled tumor protein (TCTP) is essential for survival by mechanisms that as yet are incompletely defined. Here we describe an important role of TCTP in response to DNA damage. Upon exposure of normal human cells to low-dose γ rays, the TCTP protein level was greatly increased, with a significant enrichment in nuclei. TCTP up-regulation occurred in a manner dependent on ataxia-telangiectasia mutated (ATM) kinase and the DNA-dependent protein kinase and was associated with protective effects against DNA damage. In chromatin of irradiated cells, coimmunoprecipitation experiments showed that TCTP forms a complex with ATM and γH2A.X, in agreement with its distinct localization with the foci of the DNA damage-marker proteins γH2A.X, 53BP1, and P-ATM. In cells lacking TCTP, repair of chromosomal damage induced by γ rays was compromised significantly. TCTP also was shown to interact with p53 and the DNA-binding subunits, Ku70 and Ku80, of DNA-dependent protein kinase. TCTP knockdown led to decreased levels of Ku70 and Ku80 in nuclei of irradiated cells and attenuated their DNA-binding activity. It also attenuated the radiation-induced G1 delay but prolonged the G2 delay. TCTP therefore may play a critical role in maintaining genomic integrity in response to DNA-damaging agents.

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Role of the translationally controlled tumor protein in DNA damage sensing and repair

Magnetic nanoparticles based hyperthermia therapy is a possible low cost and effective technique for killing cancer tissues in the human body. Fe3O4 and Fe3O4@YPO4:5Eu hybrid magnetic nanoparticles are prepared by co-precipitation method and their average particle sizes are found to be ∼10 and 25 nm, respectively. The particles are spherical, non-agglomerated and highly dispersible in water. The crystallinity of as-prepared YPO4:5Eu sample is more than Fe3O4@YPO4:5Eu hybrid magnetic nanoparticles. The chemical bonds interaction between Fe3O4 and YPO4:5Eu is confirmed through Fe⋯O–P. The magnetization of hybrid nanocomposite shows magnetization Ms = 11.1 emu g−1 with zero coercivity (measured at 2 × 10−4 Oe) at room temperature indicating superparamagnetic behaviour. They attain hyperthermia temperature (∼42 °C) under AC magnetic field showing characteristic induction heating of the prepared nanohybrid and they will be potential material for biological application. Samples produce the red emission peaks at 618 nm and 695 nm, which are in range of biological window. The quantum yield of YPO4:5Eu sample is found to be 12%. Eu3+ present on surface and core could be distinguished from luminescence decay study. Very high specific absorption rate up to 100 W g−1 could be achieved. The intracellular uptake of nanocomposites is found in mouse fibrosarcoma (Wehi 164) tumor cells by Prussian blue staining.

Bi-functional properties of Fe3O4@YPO4:Eu hybrid nanoparticles: hyperthermia application

Autocrine IL-8 and VEGF mediate epithelial–mesenchymal transition and invasiveness via p38/JNK-ATF-2 signalling in A549 lung cancer cells

Glucose reacts with the amino groups of protein to form a Schiff base that rearranges to form a ketoamine adduct. These early products eventually undergo irreversible chemical modifications generating advanced glycation end products (AGES). We reacted various sugars and sugar phosphates with bovine serum albumin allowing the formation of Amadori and AGE products. The rates of browning, Amadori and AGE products formed during incubations at 37 and 55 degrees C were compared. The correlation between AGE fluorescence and bitopical (crosslinking) modifications in the protein have been evaluated. Pentoses generated maximum Amadori products. Sugar phosphates were found to be more potent in generating AGEs than free sugars as measured by fluorescence. Though glucose, fructose and glucose-6-P do not generate fluorescence comparable to pentoses, they generate high molecular weight aggregates. In contrast, ribose-5-P, which shows significantly higher AGE and pentosidine fluorescence than the other sugars, did not generate high molecular weight aggregates. We suggest that there may not be a direct correlation between the levels of Amadori products, AGEs and crosslinking.

Badri N. Pandey

Papers

pH-Responsive Peptide Mimic Shell Cross-Linked Magnetic Nanocarriers for Combination Therapy

Role of the translationally controlled tumor protein in DNA damage sensing and repair

Bi-functional properties of Fe3O4@YPO4:Eu hybrid nanoparticles: hyperthermia application

Autocrine IL-8 and VEGF mediate epithelial–mesenchymal transition and invasiveness via p38/JNK-ATF-2 signalling in A549 lung cancer cells

Amadori product and age formation during nonenzymatic glycosylation of bovine serum albumin in vitro.