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D. X. G. Divaris

Bio: D. X. G. Divaris is an academic researcher from Queen's University. The author has contributed to research in topics: Fluorescence microscope & Sebaceous gland. The author has an hindex of 1, co-authored 1 publications receiving 350 citations.

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TL;DR: The skin of albino mice given 5-aminolevulinic acid by intraperitoneal injection rapidly developed the characteristic red fluorescence of protoporphyrin IX and appeared to recover completely except for a persistent reduction in the number of hair follicles.
Abstract: The skin of albino mice given 5-aminolevulinic acid (ALA) by intraperitoneal injection rapidly developed the characteristic red fluorescence of protoporphyrin IX. Fluorescence microscopy of frozen tissue sections revealed intense red fluorescence within the sebaceous glands and a much weaker fluorescence within the epidermis and hair follicles. Little or no fluorescence was detected in the dermis, blood vessels, or cartilage of the ear. Light microscopy of skin taken at intervals after whole-body exposure of ALA-injected mice to photoactivating light revealed destruction of sebaceous cells, focal epidermal necrosis with a transient acute inflammation, and diffuse reactive changes in the keratinocytes. The dermis showed transient secondary edema and inflammation. The location and severity of the phototoxic damage correlated well with the location and intensity of the red fluorescence. The light-exposed skin appeared to recover completely except for a persistent reduction in the number of hair follicles.

354 citations


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Journal ArticleDOI
TL;DR: Preclinical studies in experimental animals and human volunteers indicate that ALA can induce a localized tissue-specific photosensitization if administered by intradermal injection, opening the possibility of using ALA-induced PpIX to treat tumors that are too thick or that lie too deep to be accessible to either topical or locally injected ALA.
Abstract: The tissue photosensitizer protoporphyrin IX (PpIX) is an immediate precursor of heme in the biosynthetic pathway for heme. In certain types of cells and tissues, the rate of synthesis of PpIX is determined by the rate of synthesis of 5-aminolevulinic acid (ALA), which in turn is regulated via a feedback control mechanism governed by the concentration of free heme. The presence of exogenous ALA bypasses the feedback control, and thus may induce the intracellular accumulation of photosensitizing concentrations of PpIX. However, this occurs only in certain types of cells and tissues. The resulting tissue-specific photosensitization provides a basis for using ALA-induced PpIX for photodynamic therapy. The topical application of ALA to certain malignant and non-malignant lesions of the skin can induce a clinically useful degree of lesion-specific photosensitization. Superficial basal cell carcinomas showed a complete response rate of approximately 79% following a single exposure to light. Recent preclinical studies in experimental animals and human volunteers indicate that ALA can induce a localized tissue-specific photosensitization if administered by intradermal injection. A generalized but still quite tissue-specific photosensitization may be induced if ALA is administered by either subcutaneous or intraperitoneal injection or by mouth. This opens the possibility of using ALA-induced PpIX to treat tumors that are too thick or that lie too deep to be accessible to either topical or locally injected ALA.

1,209 citations

Journal ArticleDOI
15 Jun 1997-Cancer
TL;DR: Studies have shown that a higher accumulation of ALA‐derived PpIX in rapidly proliferating cells may provide a biologic rationale for clinical use of ALa‐based PDT and diagnosis, however, no review updating the clinical data has appeared so far.
Abstract: BACKGROUND Photodynamic therapy (PDT) for cancer patients has developed into an important new clinical treatment modality in the past 25 years PDT involves administration of a tumor-localizing photosensitizer or photosensitizer prodrug (5-aminolevulinic acid [ALA], a precursor in the heme biosynthetic pathway) and the subsequent activation of the photosensitizer by light Although several photosensitizers other than ALA-derived protoporphyrin IX (PpIX) have been used in clinical PDT, ALA-based PDT has been the most active area of clinical PDT research during the past 5 years Studies have shown that a higher accumulation of ALA-derived PpIX in rapidly proliferating cells may provide a biologic rationale for clinical use of ALA-based PDT and diagnosis However, no review updating the clinical data has appeared so far METHODS A review of recently published data on clinical ALA-based PDT and diagnosis was conducted RESULTS Several individual studies in which patients with primary nonmelanoma cutaneous tumors received topical ALA-based PDT have reported promising results, including outstanding cosmetic results However, the modality with present protocols does not, in general, appear to be superior to conventional therapies with respect to initial complete response rates and long term recurrence rates, particularly in the treatment of nodular skin tumors Topical ALA-PDT does have the following advantages over conventional treatments: it is noninvasive; it produces excellent cosmetic results; it is well tolerated by patients; it can be used to treat multiple superficial lesions in short treatment sessions; it can be applied to patients who refuse surgery or have pacemakers and bleeding tendency; it can be used to treat lesions in specific locations, such as the oral mucosa or the genital area; it can be used as a palliative treatment; and it can be applied repeatedly without cumulative toxicity Topical ALA-PDT also has potential as a treatment for nonneoplastic skin diseases Systemic administration of ALA does not seem to be severely toxic, but the advantage of using this approach for PDT of superficial lesions of internal hollow organs is still uncertain The ALA-derived porphyrin fluorescence technique would be useful in the diagnosis of superficial lesions of internal hollow organs CONCLUSIONS Promising results of ALA-based clinical PDT and diagnosis have been obtained The modality has advantages over conventional treatments However, some improvements need to be made, such as optimization of parameters of ALA-based PDT and diagnosis; increased tumor selectivity of ALA-derived PpIX; better understanding of light distribution in tissue; improvement of light dosimetry procedure; and development of simpler, cheaper, and more efficient light delivery systems Cancer 1997; 79:2282-308 © 1997 American Cancer Society

1,000 citations

Journal ArticleDOI
TL;DR: The data show that, when properly used, PDT is an effective alternative treatment option in oncology and is slowly gaining acceptance as an alternative to conventional cancer therapies.
Abstract: Photodynamic therapy (PDT) is increasingly being recognized as an attractive, alternative treatment modality for superficial cancer. Treatment consists of two relatively simple procedures: the administration of a photosensitive drug and illumination of the tumor to activate the drug. Efficacy is high for small superficial tumors and, except for temporary skin photosensitization, there are no long-term side effects if appropriate protocols are followed. Healing occurs with little or no scarring and the procedure can be repeated without cumulative toxicity. Considering the efficacy and lack of long-term toxicity of PDT, and the fact that the first treatment of cancer with PDT was done more than 100 years ago, one might expect that this treatment had already become an established therapy. However, PDT is currently offered in only a few selected centers, although it is slowly gaining acceptance as an alternative to conventional cancer therapies. Here, we show the developmental steps PDT underwent and summarize the current clinical applications. The data show that, when properly used, PDT is an effective alternative treatment option in oncology.

653 citations

Journal ArticleDOI
TL;DR: It is suggested that 5-aminolevulinic acid-induced porphyrin fluorescence may label malignant gliomas safely and accurately enough to enhance the completeness of tumor removal.
Abstract: Objective Survival after surgery and radiotherapy for the treatment of malignant gliomas is linked to the completeness of tumor removal. Therefore, methods that permit intraoperative identification of residual tumor tissue may be of benefit. In a preliminary investigation, we have studied the value of fluorescent porphyrins that accumulate in malignant tissue after administration of a precursor (5-aminolevulinic acid) for labeling of malignant gliomas in nine patients. Methods Three hours before the induction of anesthesia, 10 mg 5-aminolevulinic acid/kg body weight was administered orally. Intraoperatively, red porphyrin fluorescence was observed with a 455-nm long-pass filter after excitation with violet-blue (375-440 nm) xenon light and was verified by analysis of fluorescence spectra. Fluorescing and nonfluorescing samples taken from the tumor perimeters were examined histologically or used to study the photobleaching of porphyrins by excitation light and white light from the operating microscope. Plasma and erythrocyte porphyrin levels were determined by fluorescence photometry. Results Normal brain tissue revealed no porphyrin fluorescence, whereas tumor tissue was distinguished by bright red fluorescence. For a total of 89 tissue biopsies, sensitivity was 85% and specificity was 100% for the detection of malignant tissue. For seven of nine patients, visible porphyrin fluorescence led to further resection of the tumor. Under operating light conditions, fluorescence decayed to 36% in 25 minutes for violet-blue light and in 87 minutes for white light. Plasma and erythrocyte porphyrin contents increased slightly, without exceeding normal levels. Conclusion Our observations suggest that 5-aminolevulinic acid-induced porphyrin fluorescence may label malignant gliomas safely and accurately enough to enhance the completeness of tumor removal.

636 citations

Journal ArticleDOI
TL;DR: This review traces the origins and development of PD and PDT from antiquity to the present day and highlights the role that light has in the treatment of disease since antiquity.
Abstract: Light has been employed in the treatment of disease since antiquity. Many ancient civilizations utilized phototherapy, but it was not until early last century that this form of therapy reappeared. Following the scientific discoveries by early pioneers such as Finsen, Raab and Von Tappeiner, the combination of light and drug administration led to the emergence of photochemotherapy as a therapeutic tool. The isolation of porphyrins and the subsequent discovery of their tumor-localizing properties and phototoxic effects on tumor tissue led to the development of modern photodetection (PD) and photodynamic therapy (PDT). This review traces the origins and development of PD and PDT from antiquity to the present day.

620 citations