Biomedical subjects

Thomas J Dougherty

Publications and source records attributed to Thomas J Dougherty.

24 records · Page 2Linked to original sources

PubMed2002

An update on photodynamic therapy applications.

Photodynamic therapy (PDT), following health agency approvals throughout the world for various cancers and other diseases, is slowly being accepted as a standard treatment to be added to the medical practitioner's armamentarium. This includes palliative treatments such as for obstructive esophageal and lung cancers as well as those intended for cure, early stage lung cancer, and actinic keratoses. A particularly new and important application is for the treatment of age-related macular degeneration (AMD), where PDT (Visudyne) has made a major impact on the outcome of this disease, the major cause of blindness in those over the age of 50. In the cancer field, while not yet approved (pending), the use of PDT in treatment of high-grade dysplasia (HGD) in Barrett's esophagus may well change how this disease is currently treated (often esophagectomy). Mechanistically, the recognition of apoptosis as an important mode of cell death following PDT and the critical role of the inflammatory process and immunity has only recently been recognized. This review updates the current and future role of PDT in cancer and other diseases.

Clinical Trials as Topic↗

PubMed2002

Direct quantitation of the numbers of individual penicillin-binding proteins per cell in Staphylococcus aureus.

The penicillin-binding proteins (PBPs) are a set of enzymes that participate in bacterial peptidoglycan assembly. The absolute numbers of each PBP were determined by direct measurement and have been reported for two Staphylococcus aureus strains, RN4220 (methicillin-sensitive S. aureus) and RN450M (methicillin-resistant S. aureus). From the specific activity of the labeled penicillin and the absolute number of disintegrations per minute, and from the number of CFU per milliliter calculated from proteins and optical density, a determination of the number of PBPs per cell was made. These numbers ranged from approximately 150 to 825 PBPs/cell and represent the first direct determination of absolute numbers of PBPs in S. aureus.

Bacterial Proteins↗

PubMed2002

The role of the peripheral benzodiazepine receptor in photodynamic activity of certain pyropheophorbide ether photosensitizers: albumin site II as a surrogate marker for activity.

A study has been carried out to define the importance of the peripheral benzodiazepine receptor (PBR) as a binding site for a series of chlorin-type photosensitizers, pyropheophorbide-a ethers, the subject of a previous quantitative structure-activity relationship study by us. The effects of the PBR ligand PK11195 on the photodynamic activity have been determined in vivo for certain members of this series of alkyl-substituted ethers: two of the most active derivatives (hexyl and heptyl), the least active derivative (dodecyl [C12]) and one of intermediate activity (octyl [C8]). The photodynamic therapy (PDT) effect was inhibited by PK11195 for both of the most active derivatives, but no effect on PDT activity was found for the less active C12 or C8 ethers. The inhibitory effects of PK11195 were predicted by the binding of only the active derivatives to the benzodiazepine site on albumin, ie. human serum albumin (HSA)-Site II. Thus, as with certain other types of photosensitizers, it has been demonstrated with this series of pyropheophorbide ethers that in vitro binding to HSA-Site II is a predictor of both optimal in vivo activity and binding to the PBR in vivo.

Animals↗

PubMed2002

A first comparative study of purpurinimide-based fluorinated vs. nonfluorinated photosensitizers for photodynamic therapy.

A first report on the synthesis and comparative in vitro-in vivo photosensitizing efficacy of various fluorinated and the corresponding nonfluorinated, purpurinimide-based photosensitizers is discussed. In preliminary in vivo screening, compared with the nonfluorinated analogs, purpurinimides bearing trifluoromethyl substituents showed enhanced photosensitizing efficacy. Among compounds (isomers) with similar lipophilicity, the position of the substituents was found to play a decisive role in biological efficacy.

Animals↗

PubMed2002

Microbial genomics and novel antibiotic discovery: new technology to search for new drugs.

The process of prokaryotic drug discovery has been a model of success for over fifty years, yet the number of exploited bacterial targets is a mere fraction, less than 0.1% of the potential targets (based on total number of bacterial genes identified by gene sequence projects). To better understand the potential for drug intervention, multiple paradigms have been established in the pharmaceutical industry, all with some semblance of commonality and uniqueness to provide proprietary positioning, yet no company has been successful to date in taking a genomics approach to the finish line of having a genomics-based drug on the market. Within this overview, we provide a strategic overview of a sample process for the identification, validation and exploitation of novel antibacterial targets ascertained through a bioinformatics-based genomics drug discovery program.

Anti-Bacterial Agents↗

PubMedDate not supplied

Photodynamic therapy for sarcoma pulmonary metastases: a preclinical toxicity study.

BACKGROUND: Intraoperative pleural and interstitial PDT accompanying resection may reduce peripheral micrometastatic foci and preclude lobectomy when applied to hilar lesions. MATERIALS AND METHODS: Fourteen beagles were used to determine the safety and histologic changes resulting from PDT. Photosensitizers HPPH (0.3 mg/kg) or Photofrin (2.0 mg/kg) were administered i.v. 48 hours prior to thoracotomy and light delivery. At thoracotomy interstitial or pleural light was given. They underwent necropsy at eight and 30 days. RESULTS: The significant toxicitities occurred with pleural PDT using high dose HPPH (15 & 30 J/cm2) including pyrexia, elevated WBC and CPK, and respiratory distress. However, using single beam pleural surface treatment all light doses for HPPH and Photofrin (5-40 J/cm2) were tolerated with depths of treatment effect up to 10 mm with HPPH. CONCLUSION: Histologic and clinical changes associated with interstitial and pleural PDT were acceptable after dosimetry was adjusted. PDT holds promise as an adjuvant treatment for sarcoma pulmonary metastases.

Animals↗