Oncolytic herpes viruses, chemotherapeutics, and other cancer drugs

Oncolytic viruses are emerging as a potential new way of treating cancers. They are selectively replication-competent viruses that propagate only in actively dividing tumor cells but not in normal cells and, as a result, destroy the tumor cells by consequence of lytic infection. At least six different oncolytic herpes simplex viruses (oHSVs) have undergone clinical trials worldwide to date, and they have demonstrated an excellent safety profile and intimations of efficacy. The first pivotal Phase III trial with an oHSV, talimogene laherparepvec (T-Vec [OncoVex<sup>GM-CSF</sup>]), is almost complete, with extremely positive early results reported. Intuitively, therapeutically beneficial interactions between oHSV and chemotherapeutic and targeted therapeutic drugs would be limited as the virus requires actively dividing cells for maximum replication efficiency and most anticancer agents are cytotoxic or cytostatic. However, combinations of such agents display a range of responses, with antagonistic, additive, or, perhaps most surprisingly, synergistic enhancement of antitumor activity. When synergistic interactions in cancer cell killing are observed, chemotherapy dose reductions that achieve the same overall efficacy may be possible, resulting in a valuable reduction of adverse side effects. Therefore, the combination of an oHSV with “standard-of-care” drugs makes a logical and reasonable approach to improved therapy, and the addition of a targeted oncolytic therapy with “standard-of-care” drugs merits further investigation, both preclinically and in the clinic. Numerous publications report such studies of oncolytic HSV in combination with other drugs, and we review their findings here. Viral interactions with cellular hosts are complex and frequently involve intracellular signaling networks, thus creating diverse opportunities for synergistic or additive combinations with many anticancer drugs. We discuss potential mechanisms that may lead to synergistic interactions

Could your school have a STEM emphasis?

There are various descriptions of STEM (Science, Technology, Engineering and Mathematics education around the world. In the USA it includes the fields of Chemistry, Computer and Information Technology Science, Engineering, Geosciences, Life Sciences, Mathematical Sciences, Physics, and STEM Education and Learning Research. Partly differences in what is included in STEM arise due to different views of technology and the levels of integration of the subjects as they are combined or not, in curricula design. In the international arena, technology tends to be synonymous with ICT. In New Zealand, we have a separate subject domain called technology that includes design for innovation through technological practice, knowledge, and understanding about the nature of technology. Effective communication, including the use of information technology, collaboration, problem-solving, creative and critical thinking skills are fundamental to STEM

Melt infiltration casting of bulk metallic-glass matrix composites

The authors describe a technique for melt infiltration casting of composites with a metallic-glass matrix. We made rods 5 cm in length and 7 mm in diameter. The samples were reinforced by continuous metal wires, tungsten powder, or silicon carbide particulate preforms. The most easily processed composites were those reinforced with tungsten and carbon steel continuous wire reinforcement. The Zr41.2Ti13.8Cu12.5Ni10.0Be22.5 matrix was quenched to a glass after infiltrating the reinforcement. We analyzed the microstructure of the composites by x-ray diffraction and scanning electron microscopy. The measured porosity was less than 3% and the matrix was about 97% amorphous material

Mechanical properties of Zr_(57)Nb_5Al_(10)Cu_(15.4)Ni_(12.6) metallic glass matrix particulate composites

To increase the toughness of a metallic glass with the nominal composition Zr_(57)Nb_5Al_(10)Cu_(15.4)Ni_(12.6), it was used as the matrix in particulate composites reinforced with W, WC, Ta, and SiC. The composites were tested in compression and tension experiments. Compressive strain to failure increased by more than 300% compared with the unreinforced Zr_(57)Nb_5Al_(10)Cu_(15.4)Ni_(12.6), and energy to break of the tensile samples increased by more than 50%. The increase in toughness came from the particles restricting shear band propagation, promoting the generation of multiple shear bands and additional fracture surface area. There was direct evidence of viscous flow of the metallic glass matrix within the confines of the shear bands