Those readers already familiar with the field of photodynamic therapy (PDT)t will consider this title somewhat presumptuous since it implies that the answer to the posed question is known. Indeed, answers to many questions regarding PDT have been found over the past decade, but a comprehensive understanding of all mechanisms involved in PDT tumor destruction has not yet emerged. This paper will attempt to deal with this complex subject by giving a sequential account of the effects occurring during PDT tissue treatment on a cellular and tissue level. Photodynamic therapy is based on the dye-sensitized photooxidation of biological matter in the target tissue (Foote, 1990). This requires the presence of a dye (sensitizer) in the tissue to be treated. Although such sensitizers can be naturally occurring constituents of cells and tissues, in the case of PDT they are introduced into the organism as the first step of treatment. In the second step, the tissuelocalized sensitizer is exposed to light of wavelength appropriate for absorption by the sensitizer. Through various photophysical pathways, also involving molecular oxygen, oxygenated products harmful to cell function arise and eventual tissue destruction results. In keeping with the chronological nature of this review, the subject matter will be divided into the

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1751-1097.1992.tb04222.x

How does photodynamic therapy work

Developing a new drug from original idea to the launch of a finished product is a complex process which can take 12-15 years and cost in excess of $1 billion. The idea for a target can come from a variety of sources including academic and clinical research and from the commercial sector. It may take many years to build up a body of supporting evidence before selecting a target for a costly drug discovery programme. Once a target has been chosen, the pharmaceutical industry and more recently some academic centres have streamlined a number of early processes to identify molecules which possess suitable characteristics to make acceptable drugs. This review will look at key preclinical stages of the drug discovery process, from initial target identification and validation, through assay development, high throughput screening, hit identification, lead optimization and finally the selection of a candidate molecule for clinical development.

/pdf/principles-of-early-drug-discovery-35zxvfs97l.pdf

Principles of early drug discovery

http://molbiol.ru/forums/index.php?act=Attach&type=post&id=75938

Fluorescence probes used for detection of reactive oxygen species

In this review we intend to provide a relatively comprehensive summary of the work of supramolecular hydrogelators after 2004 and to put emphasis particularly on the applications of supramolecular hydrogels/hydrogelators as molecular biomaterials. After a brief introduction of methods for generating supramolecular hydrogels, we discuss supramolecular hydrogelators on the basis of their categories, such as small organic molecules, coordination complexes, peptides, nucleobases, and saccharides. Following molecular design, we focus on various potential applications of supramolecular hydrogels as molecular biomaterials, classified by their applications in cell cultures, tissue engineering, cell behavior, imaging, and unique applications of hydrogelators. Particularly, we discuss the applications of supramolecular hydrogelators after they form supramolecular assemblies but prior to reaching the critical gelation concentration because this subject is less explored but may hold equally great promise for helping ...

Supramolecular Hydrogelators and Hydrogels: From Soft Matter to Molecular Biomaterials

Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer

Although the general radiobiologic principles underlying external beam therapy and radionuclide therapy are the same, there are significant differences in the radiobiologic effects observed in mammalian cells. External beam and brachytherapy emissions are composed of photons, whereas radiations of interest in radionuclide therapy are particulate. The special features that characterize the biologic effects consequent to the traversal of charged particles through mammalian cells are explored with respect to DNA lesions and cellular responses. Information about the ways in which these radionuclides are used to treat cancers in experimental models are highlighted.

https://jnm.snmjournals.org/content/jnumed/46/1_suppl/4S.full.pdf

Radiobiologic Principles in Radionuclide Therapy

http://medlib.yu.ac.kr/eur_j_oph/se_n_u/s_n_u/38_5_358.pdf

Therapeutic radionuclides: biophysical and radiobiologic principles.

Biological studies of a new class of technetium complexes: the hexakis(alkylisonitrile)technetium(I) cations

The bystander effect, originating from cells irradiated in vitro, describes the biologic response(s) of surrounding cells not directly targeted by a radiation insult. To overcome the limitations of in vitro tissue culture models and determine whether a bystander effect that is initiated by the in vivo decay of a radionuclide can be demonstrated in an animal, the ability of 5-[125I]iodo-2′-deoxyuridine (125IUdR)-labeled tumor cells to exert a damaging effect on neighboring unlabeled tumor cells growing s.c. in nude mice has been investigated. When mice are injected with a mixture of human colon LS174T adenocarcinoma cells and LS174T cells prelabeled with lethal doses of DNA-incorporated 125I, a distinct inhibitory effect on the growth of s.c. tumor (derived from unlabeled cells) is observed. Because (i) the 125I present within the cells is DNA-bound, (ii) ≈99% of the electrons emitted by the decaying 125I atoms have a subcellular range (<0.5 μm), and (iii) the overall radiation dose deposited by radiolabeled cells in the unlabeled cells within the growing tumor is <10 cGy, we conclude that the results obtained are a consequence of a bystander effect that is generated in vivo by factor(s) present within and/or released from the 125IUdR-labeled cells. These in vivo findings significantly impact the current dogma for assessing the therapeutic potential of internally administered radionuclides. They also call for reevaluation of the approaches currently used for estimating the risks to individuals and populations inadvertently exposed internally to radioactivity as well as to patients undergoing routine diagnostic nuclear medical procedures.

https://www.pnas.org/content/pnas/99/21/13765.full.pdf

Bystander effect produced by radiolabeled tumor cells in vivo

http://csmres.co.uk/cs.public.upd/article-downloads/Yang%20Adelstein%20and%20Kassis_a3138.pdf

Amin I. Kassis

Papers

Radiobiologic Principles in Radionuclide Therapy

Therapeutic radionuclides: biophysical and radiobiologic principles.

Biological studies of a new class of technetium complexes: the hexakis(alkylisonitrile)technetium(I) cations

Bystander effect produced by radiolabeled tumor cells in vivo

Target discovery from data mining approaches.