The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect.

Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect

Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity

SMANCS and polymer-conjugated macromolecular drugs: advantages in cancer chemotherapy.

Phytochrome, a red/far-red-light photoreceptor protein of plants, is encoded by a small gene family. Phytochrome A (PHYA), the product of the PHYA gene, is the predominant molecular species of phytochrome in etiolated tissue and has been best characterized biochemically. To define a role for PHYA, we isolated new mutants, designated fre1 (far-red elongated), in Arabidopsis thaliana that were specifically deficient in PHYA spectral activity and protein accumulation. These mutants were identified on the basis of their long hypocotyl phenotype under continuous far-red light. Although the fre1 mutants lacked the hypocotyl response to continuous far-red light, their responses to continuous white light and to end-of-day far-red-light treatments were normal. Thus, PHYA appears to play only a minor role in the regulation of hypocotyl elongation under natural conditions. In contrast, the fre1 mutation affected greening a fre1 mutant was less able than the wild type to deetiolate after growth in the dark. However, the potentiation effect of a red-light pulse on accumulation of chlorophyll was not changed significantly in the fre1 mutants. Thus, the function of PHYA might be highly specialized and restricted to certain phases of Arabidopsis development.

Isolation and Initial Characterization of Arabidopsis Mutants That Are Deficient in Phytochrome A

Production and Characterization of Monoclonal Antibodies Which Distinguish Different Surface Structures of Pea (Pisum sativum cv. Alaska) Phytochrome

14C-Labeled protein antibiotic neocarzinostatin (NCS) was prepared efficiently by chemical modification. With the use of lymphoma-derived cell line P3HR-1, the subcellular behavior of this antitumor antibiotic was studied by the uptake and autoradiography of isolated nuclei of radioactive NCS.

The antibiotic was taken up by the cells, reaching the maximum value at 1.5 hr and decreasing in value at 4.0 hr to the level at 0.5 hr. The silver grains in the autoradiograms were also found in the isolated nuclei. The grain count in the nuclei showed a tendency similar to the uptake of NCS by the whole cells, i.e. , a gradual increase at 0.5 hr, reaching the maximum value at 1.5 hr, and then decreasing after 4.0 hr to the level at 0.5 hr. These facts indicated that NCS reached not only to cytosol but also into the nucleus, and/or at least to the nuclear membrane of the lymphoid cell.

The number of NCS molecules incorporated into the cells at 1.5 hr was calculated to be about 1 × 106/cells at a concentration of 3 µg NCS per ml of medium, which can be extrapolated to 1 × 104 molecules per cell at the minimum inhibitory concentration. The number of molecules should be even less within the nucleus.

In cell-free systems, the interaction of DNA and NCS, which is an inhibitor of DNA synthesis, was investigated with the use of a Sephadex G-100 column, with negative results. In the cell culture system, NCS molecules were degraded into smaller polypeptides of certain sizes by proteolysis either by serum component(s) or by cells themselves.

An inactive isomer, pre-NCS, which is an antagonist of NCS and a partially denatured homologous molecule, behaved similarly to NCS in all of these experiments.

Because the chemically modified NCS used in this study retained biological activity essentially similar to that of parental NCS, the results obtained here could be interpreted as similar to those of parental NCS in vitro .

https://cancerres.aacrjournals.org/content/canres/35/3/554.full.pdf

Subcellular fate of protein antibiotic neocarzinostatin in culture of a lymphoid cell line from Burkitt's lymphoma.

Thymus of abused/neglected children

Lymphotropic accumulation of an antitumor antibiotic protein, neocarzinostatin

Mesoscopic structures of the lacrimal drainage pathway were observed under an operating microscope in six cases of 5 adult cadavers. In all these cases the upper and lower canaliculi fused to form the common canaliculus. Two cases with a large common canaliculus showed large projections of mucosa which reduced the inner space of the common canaliculus. The remaining 4 cases with a small common canaliculus did not show any projections. These findings indicate that the human lacrimal system can function physiologically through a small narrow space of the common canaliculus.

Akira Yamashita

Papers

Production and Characterization of Monoclonal Antibodies Which Distinguish Different Surface Structures of Pea (Pisum sativum cv. Alaska) Phytochrome

Subcellular fate of protein antibiotic neocarzinostatin in culture of a lymphoid cell line from Burkitt's lymphoma.

Thymus of abused/neglected children

Lymphotropic accumulation of an antitumor antibiotic protein, neocarzinostatin

Anatomical analysis of the human lacrimal drainage pathway under an operating microscope