Tumor Stimulus-Responsive Biodegradable Diblock Copolymer Conjugates as Efficient Anti-Cancer Nanomedicines.

Biodegradable nanomedicines are widely studied as candidates for the effective treatment of various cancerous diseases. Here, we present the design, synthesis and evaluation of biodegradable polymer-based nanomedicines tailored for tumor-associated stimuli-sensitive drug release and polymer system degradation. Diblock polymer systems were developed, which enabled the release of the carrier drug, pirarubicin, via a pH-sensitive spacer allowing for the restoration of the drug cytotoxicity solely in the tumor tissue. Moreover, the tailored design enables the matrix-metalloproteinases- or reduction-driven degradation of the polymer system into the polymer chains excretable from the body by glomerular filtration. Diblock nanomedicines take advantage of an enhanced EPR effect during the initial phase of nanomedicine pharmacokinetics and should be easily removed from the body after tumor microenvironment-associated biodegradation after fulfilling their role as a drug carrier. In parallel with the similar release profiles of diblock nanomedicine to linear polymer conjugates, these diblock polymer conjugates showed a comparable in vitro cytotoxicity, intracellular uptake, and intratumor penetration properties. More importantly, the diblock nanomedicines showed a remarkable in vivo anti-tumor efficacy, which was far more superior than conventional linear polymer conjugates. These findings suggested the advanced potential of diblock polymer conjugates for anticancer polymer therapeutics.

A new species of Sarsinebalia (Crustacea, Leptostraca) from Japan.

A new species of Leptostraca, Sarsinebaliaagoensis sp. nov., from Ago Bay, Japan is described from specimens found at a depth of 120 m. The new species differs from other known Sarsinebalia species as follows: the compound eye has three distal lobes; the anterior margin of the first antennal segment has one distal process covered with setae; and the lateral margin of pleopod 1 exopod bears 5-6 simple, robust spines. A taxonomic key to all species of Sarsinebalia is also provided.

A new species of Nebalia (Crustacea, Leptostraca) from a hydrothermal field in Kagoshima Bay, Japan.

A new species of Leptostraca, Nebalia tagiri sp. nov. is described and illustrated. This species was sampled from 200 m depth at a hydrothermal field in Wakamiko Caldera of Kagoshima Bay, Japan. Nebalia tagiri sp. nov. is different from known Nebalia species as follows: rostral length 2.4 times as long as width; article 4 of antennule with 3-5 robust distal spines; antennular scale approximately twice as long as wide; article 3 of antenna with eight spines and nine spine-like setae along proximal half, two thin setae and six spine-like setae on external lateral face, six spines and four simple setae on distal margin; article 1 of second maxilla longer than article 2; article 2 of mandibular palp with two thin setae; exopod of pleopod 1 with 21 spines along lateral margin; furcal rami longer than combined length of pleonite 7 and telson; rounded denticles of pleonite 6 and 7; anal-plates 'shoulder' not distinct. Furthermore, this specimen is the first genus Nebalia found in the hydrothermal vent. The distribution and ecology of this new species is also discussed and a key to all species of Nebalia is provided.

Simple and Convenient Method for the Isolation, Culture, and Re-collection of Cancer Cells from Blood by Using Glass-Bead Filters.

Circulating tumor cells (CTCs) are tumor cells that originate from primary cancer tissues, enter the bloodstream in the body, and metastasize to the other organs. Simple and convenient methods for their detection, capture, and recovery from the blood of cancer patients would be highly desirable. We report here on a simple and convenient methodology to trap, culture, and re-collect cancer cells, the sizes of which are greater than those of normal hematologic cells, by the use of glass-bead filters (GBFs). We prepared GBFs with a diameter of 24 mm and thicknesses of 0.4 mm and 1.2 mm, with well-defined pores, by sintering round-shaped glass beads (diameter: 63-106 µm). A small integrated glass-bead filter (iGBF) with a diameter of ca. 9.6 mm for the use in filtering a small volume of blood was also designed and prepared. Using GBF and iGBF, it was possible to efficiently capture mouse Lewis lung carcinoma cells expressing green fluorescent protein spiked in saline/blood by single and repeated (circulation) filtrations in in vitro experiments with very small amounts of red blood cells being captured. In addition, we successfully captured B16 CTCs from the blood of a B16 melanoma metastasis mouse model by iGBF. Cancer cells/CTCs captured on/in the GBF could be cultured and efficiently recovered from the filters. Filtration by GBF had negligible effect on the adherent and proliferative characteristics of cancer cells. Simple and convenient methods for the capture, culture, and re-collection of CTCs by GBF along with flexibility of GBF, which permits them to be molded into suitable architectures having the desired shape and size, should be useful for early and convenient diagnosis and treatment of cancer and related diseases.

Complete adult neurogenesis within a Wallerian degenerating nerve expressed as an ectopic ganglion.

Neurogenesis in the adult peripheral nervous system remains to be demonstrated. We transplanted embryonic neural stem cells into a Wallerian degenerating nerve graft and observed development of a nodular structure consisting of neurons, glia, and Schwann cells. Histological analysis revealed a structure loosely resembling the spinal cord, including a synaptic network that formed along the neuron. Furthermore, the new axons reinnervated the paralysed muscle, forming both de novo and revived neuromuscular junctions. Reinnervation of the paralysed muscle resulted in significantly greater mean wet muscle weight and muscle fibre cross-sectional area on the cell transplantation side than on the surgical control side (body weight 0.071 ± 0.011% vs. 0.051 ± 0.007%, p = .006; area 355.6 ± 345.2 vs. 114.0 ± 132.0 µm2 , p < .001). Electrophysiological experiments demonstrated a functional connection between the neurons and muscle; hence, we identified this nodule as an ectopic ganglion. Surprisingly, in green rat experiments, most of these glial cells, but none of the neurons, expressed enhanced green fluorescent protein, suggesting that the cells constituting the ectopic ganglion were derived from both transplanted stem cells and endogenous stem cells. Such adult neurogenesis in a peripheral nerve related to neural stem cell transplantation has not been reported previously, and these results form the basis for a novel regenerative medicine approach in paralysed muscle.