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Biomedical subjects

T Warloe

Publications and source records attributed to T Warloe.

At least 19 recordsLinked to original sources
PubMed2007

Phototoxic reaction and porphyrin fluorescence in skin after topical application of methyl aminolaevulinate.

BACKGROUND: Photodynamic therapy using topical methyl aminolaevulinate (MAL) is a new treatment modality for skin disorders. MAL is metabolized into endogenous porphyrins, which act as photosensitizers when illuminated. OBJECTIVES: To evaluate the severity and duration of skin photosensitivity after MAL application, and to investigate its relation to the presence of endogenous porphyrins. METHODS: Placebo and 160 mg g(-1) MAL creams were randomly assigned to contralateral sites located at the forearms and fingertips of 16 healthy volunteers and were applied for 3 h. The porphyrin content in the skin was monitored by in situ fluorescence measurements following cream removal. Phototoxic reaction was evaluated after exposure to a high dose of red light. RESULTS: The porphyrin fluorescence in forearm skin peaked about 1 h after the cream removal, was halved after 8 h, and was reduced by > 90% within 24 h. Most forearm sites were photosensitive at 1 and 8 h following cream removal. Six subjects were still sensitive at 24 h, and at this time point the phototoxicity was coincidental with residual porphyrin fluorescence. In general, all reactions were mild or moderate, and included pain, erythema, oedema and transient hyperpigmentation. No photosensitivity or porphyrin fluorescence was detected at 48 h. At the fingertips photosensitivity was absent except for sporadic cases of mild pain. CONCLUSIONS: Topical MAL application and exposure to red light induced mild and moderate phototoxicity. The photosensitivity ceased within 24-48 h after cream removal, and its duration was associated with the degradation of porphyrins.

Administration, Topical↗
PubMed2005

Porphyrin-related photosensitizers for cancer imaging and therapeutic applications.

A photosensitizer is defined as a chemical entity, which upon absorption of light induces a chemical or physical alteration of another chemical entity. Some photosensitizers are utilized therapeutically such as in photodynamic therapy (PDT) and for diagnosis of cancer (fluorescence diagnosis, FD). PDT is approved for several cancer indications and FD has recently been approved for diagnosis of bladder cancer. The photosensitizers used are in most cases based on the porphyrin structure. These photosensitizers generally accumulate in cancer tissues to a higher extent than in the surrounding tissues and their fluorescing properties may be utilized for cancer detection. The photosensitizers may be chemically synthesized or induced endogenously by an intermediate in heme synthesis, 5-aminolevulinic acid (5-ALA) or 5-ALA esters. The therapeutic effect is based on the formation of reactive oxygen species (ROS) upon activation of the photosensitizer by light. Singlet oxygen is assumed to be the most important ROS for the therapeutic outcome. The fluorescing properties of the photosensitizers can be used to evaluate their intracellular localization and treatment effects. Some photosensitizers localize intracellularly in endocytic vesicles and upon light exposure induce a release of the contents of these vesicles, including externally added macromolecules, into the cytosol. This is the basis for a novel method for macromolecule activation, named photochemical internalization (PCI). PCI has been shown to potentiate the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins, immunotoxins, gene-encoding plasmids, adenovirus, peptide-nucleic acids and the chemotherapeutic drug bleomycin. The background and present status of PDT, FD and PCI are reviewed.

Animals↗
PubMed2003

Topical methyl aminolaevulinate photodynamic therapy in patients with basal cell carcinoma prone to complications and poor cosmetic outcome with conventional treatment.

BACKGROUND: Conventional treatment of basal cell carcinoma (BCC) causes morbidity and/or disfigurement in some patients because of the location (e.g. mid-face) and size of the lesion. OBJECTIVES: Following reports that such difficult-to-treat BCC lesions have been treated successfully with topical methyl aminolaevulinate (MAL) photodynamic therapy (PDT), a multicentre study was performed to determine the response of such BCC to MAL-PDT. METHODS: An open, uncontrolled, prospective, multicentre study was conducted comprising patients with superficial and/or nodular BCC who were at risk of complications, poor cosmetic outcome, disfigurement and/or recurrence using conventional therapy. Patients were given one or two cycles within 3 months of topical MAL-PDT, each consisting of two treatments 1 week apart. Tumour response was assessed clinically at 3 months after the last PDT, with histological confirmation of all lesions in clinical remission. The cosmetic outcome was rated. Patients with a BCC in remission will be followed up for 5 years for recurrence, of which the 24-month follow-up is reported here. Ninety-four patients with 123 lesions were enrolled and treated with MAL-PDT at nine European primary care and referral university hospitals. An independent blinded study review board (SRB) retrospectively excluded nine patients and a total of 15 lesions from the efficacy analysis, for not having a difficult-to-treat BCC according to the protocol. RESULTS: The lesion remission rate at 3 months was 92% (45 of 49) for superficial BCC, 87% (45 of 52) for nodular BCC, and 57% (four of seven) for mixed BCC, as assessed by clinical examination, and 85% (40 of 47), 75% (38 of 51), and 43% (three of seven), respectively, as assessed by histological examination and verified by the SRB. At 24 months after treatment, the overall lesion recurrence rate was 18% (12 of 66). The cosmetic outcome was graded as excellent or good by the investigators in 76% of the cases after 3 months follow-up, rising to 85% at 12 months follow-up, and 94% at 24 months follow-up. CONCLUSIONS: Topical MAL-PDT is effective in treating BCC at risk of complications and poor cosmetic outcome using conventional therapy. MAL-PDT preserves the skin and shows favourable cosmetic results.

Administration, Topical↗
PubMed2001

[Diagnosis and treatment of oral precancerous lesions].

BACKGROUND: Risk factors for oral carcinomas have been identified, but there are no reliable markers for assessing the clinical outcome in individual patients with oral precancerous lesions. DNA aneuploidy is now recognized as an early and significant event in carcinogenesis. METHODS: We identified 242 patients with oral red or white patches histologically verified as epithelial dysplasias and measured the nuclear DNA content (DNA ploidy) of the lesions to determine whether DNA ploidy could be used to predict the clinical outcome. Disease-free survival was assessed in relation to DNA ploidy and histological grade. The mean duration of follow-up was approximately eight years. RESULTS: Among 242 patients with verified epithelial dysplasia, a carcinoma developed in 48 (20%). 167 (69%) had diploid lesions, 20 (8%) had tetraploid lesions and 55 (23%) had aneuploid lesions. Of the 167 with diploid lesions, only four (1%) later developed an oral carcinoma. By contrast, 48 of 55 patients with aneuploid lesions (87%) later developed a carcinoma. INTERPRETATION: The DNA content (DNA ploidy) can be used to predict the risk for oral cancer in a wide range of oral precancerous lesions. By contrast, histological grading of the same lesions does not give any prognostic information. The clinical value of an early identification of oral lesions with malignant cell clones is substantiated by the fact that there are methods for early intervention.

Aneuploidy↗
PubMed2001

Selective distribution of porphyrins in skin thick basal cell carcinoma after topical application of methyl 5-aminolevulinate.

Topical photodynamic therapy (PDT) of superficial basal cell carcinoma (BCC) with 5-aminolevulinic acid (ALA) has achieved promising clinical results. However, the efficacy of this therapy for thick BCC is dramatically decreased by a limited diffusion of hydrophilic ALA into the tumor. Lipophilic esters of ALA may enhance their penetration into the lesion. In this randomized, open clinical study, microscopic fluorescence photometry incorporating a light-sensitive thermo-electrically cooled charge-coupled device (CCD) camera was employed to investigate the penetration of methyl 5-aminolevulinate-induced porphyrin fluorescence in thick BCC lesions. Both the distribution pattern and the amount of porphyrins in 32 lesions of 16 patients were studied after topical application of 16, 80 or 160 mg/g of methyl 5-aminolevulinate for 3 or 18 h. A highly selective and homogeneous distribution of methyl 5-aminolevulinate-induced porphyrin fluorescence was seen in all lesions studied, with much less fluorescence in the adjacent normal skin tissues. In lesions of up to 2 mm thickness the application of 160 mg/g methyl 5-aminolevulinate for 3 h showed the highest ratio of porphyrin fluorescence depth to tumor depth (0.98+/-0.04), thus providing a biologic rationale for a clinical PDT trial with this regimen.

Administration, Topical↗
PubMed2001

Antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy can be enhanced by the use of a low dose of photofrin in human tumor xenografts.

Practically all of the exogenous photosensitizers used for clinical photodynamic therapy (PDT) target mainly vasculature. Although effective in tumor destruction, they also, unavoidably, induce phototoxicity of normal tissues. Porphyrins synthesized endogenously from 5-aminolevulinic acid (ALA) accumulate within cells. Tumor eradication would be more efficient if both cellular components and vascular stroma of a tumor could be targeted. Thus, PDT with a mixture of ALA and Photofrin (Pf, a vessel-targeted sensitizer) may simultaneously destroy the two elements. Using chemical extraction assays, pharmacokinetics of ALA and ALA-induced porphyrins were studied in the plasma and tumors of nude mice bearing human WiDr and KM20L2 colonic carcinomas after an i.p. injection of 250 mg/kg body weight of ALA. Subsequently, PDT efficacy of the two tumor models with ALA, Pf, or with the two drugs in combination was evaluated. The phototoxic effects on tumor cells in vitro with the combined drugs was also determined. Moreover, histological and ultrastructural alterations of the treated tumors were investigated, and tumor cell clonogenicity was assessed as a function of time after in vivo PDT using an in vitro colony formation assay. Finally, the photosensitivity of normal skin tissue treated according to various protocols was compared. The amounts of ALA peaked at 0.5 h after administration in both plasma and WiDr tumor. The rates of ALA clearance seemed to follow a one-compartment model with half-lives of approximately 18 and 58 min in the plasma and tumor, respectively. About 100 and 60 times higher concentrations of ALA were needed to induce a given concentration of porphyrins in the plasma and tumor, respectively, although the plasma porphyrins may not only be released from blood cells but also from other organs. Similar kinetics of distribution patterns of ALA- and ALA methylester-induced porphyrins were found in the plasma and tumors, and the elimination rates were consistent with a two-compartment model. ALA induced much more porphyrins than ALA methylester in both plasma and tumors. Tumors PDT-treated with ALA plus Pf at a low dose (1 mg/kg) grew significantly more slowly than those treated with either of the drugs in both WiDr and KM20L2 models. However, the enhanced antitumor effect was not found in the tumor cells under in vitro conditions. Morphological studies demonstrated that PDT with the combined regimen resulted in necrosis of neoplastic cells and severe disruption of tumor microvasculature. This was supported by the findings obtained from the studies of in vivo PDT and in vitro clonogenic assay that showed a progressive reduction in tumor cell viability with times following PDT. Such a combined PDT protocol did not induce any phototoxicity in normal skin tissue. These data indicate that targeting both neoplastic cells and stroma with ALA and Pf (a low dose) can potentiate antitumor PDT effect with no risk of prolonged skin photosensitivity.

Adenocarcinoma↗
PubMed2001

A follow-up study of recurrence and cosmesis in completely responding superficial and nodular basal cell carcinomas treated with methyl 5-aminolaevulinate-based photodynamic therapy alone and with prior curettage.

BACKGROUND: Methyl 5-aminolaevulinate (mALA) is an ester derivative of 5-aminolaevulinic acid (ALA) with increased lipophilicity compared with ALA. OBJECTIVES: To assess long-term cure rate, cosmesis, recurrence rate and extent of fibrosis after mALA-based photodynamic therapy (PDT) of superficial and nodular basal cell carcinomas (BCCs) showing early complete response to treatment. METHODS: Of 350 BCCs treated, 310 responded completely. These were in 59 patients who were followed for 2-4 years (mean 35 months) after mALA-PDT. Nodular tumours were curetted before PDT, and mALA 160 mg g(-1) was applied to all tumours for 24 h or 3 h before illumination from a broad-band halogen light source with light doses from 50 to 200 J cm(-2). Fibrosis was assessed histologically in 23 biopsies. RESULTS: The overall cure rate for 350 BCCs, including non-responders and recurrences was 79%. Of 310 lesions, 277 (89%) remained in complete response, and the cosmetic outcome was excellent or good in 272 of the completely responding lesions (98%). Histological examination showed dermal fibrosis in one of 23 biopsies. CONCLUSIONS: We conclude that mALA-based PDT with prior curettage of nodular lesions is a promising new method for the treatment of BCC.

Aged↗
PubMed2000

Photodynamic therapy of residual or recurrent basal cell carcinoma after radiotherapy using topical 5-aminolevulinic acid or methylester aminolevulinic acid.

This study was conducted to assess the efficacy of aminolevulinic acid-based photodynamic treatment for residual or recurrent basal cell carcinomas after radiotherapy. Photodynamic therapy with either topical 5-aminolevulinic acid 20% and dimethylsulfoxide 99% pretreatment or topical methylester aminolevulinic acid 20% w/w in cream and subsequent light illumination of 50-200 J/cm2 was performed after an initial skin shaving procedure in 20 patients with 22 residual or recurrent basal cell carcinomas. Three lesions were treated once, while twelve, three, one and two lesions received two, three, four and five treatment sessions respectively. At examination, 6-40 months (mean 22 months) after the last treatment, 18 lesions were in complete remission. All lesions were considered excellent or good with regard to cosmetic outcome. Three lesions responded only partially to photodynamic therapy and a fourth lesion recurred 21 months after photodynamic treatment. Two of these four lesions were confirmed as the morpheaform type of basal cell carcinoma.

Administration, Topical↗
PubMed2000

Photodynamic therapy of superficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid: a comparison of two light sources.

The aim of this prospective randomized study was to compare the clinical and cosmetic outcome of superficial basal cell carcinomas (BCC), using either laser or broadband halogen light, in photodynamic therapy with topical 5-aminolevulinic acid (ALA). A total of 83 patients with 245 superficial BCC were included in the study. Standard treatment involved 15 min of local pretreatment with 99% dimethylsulfoxide (DMSO) before topical application of 20% ALA with DMSO (2%) and ethylendiaminetetraacetic acid (2%) as cofactors for 3 h before light exposure with either laser or a broadband lamp (BL). A complete response was achieved in 95 lesions (86%) in the laser group and 110 lesions (82%) in the BL group 6 months after treatment. Of these, 80 lesions (84%) in the laser group and 101 lesions (92%) in the lamp group were independently evaluated to have an excellent or good cosmetic post-treatment score. No serious adverse events were reported. This study shows that there is no statistical significant difference in cure the rate (P = 0.49) and the cosmetic outcome (P = 0.075) with topical application of a modified ALA-cream between light exposure from a simple BL with continuous spectrum (570-740 nm) or from a red-light laser (monochromatic 630 nm). Cost and safety are further elements in favor of the BL in this setting.

Aminolevulinic Acid↗
PubMed1999

Photodynamic therapy by topical aminolevulinic acid, dimethylsulphoxide and curettage in nodular basal cell carcinoma: a one-year follow-up study.

Fifty-eight patients with 119 nodular (2 mm or more in thickness) basal cell carcinomas successfully treated with photodynamic therapy were included in this 1-year follow-up study. The initial cure rate at 3-6 months was 92% after photodynamic therapy, which included an initial debulking procedure and topical application of dimethylsulphoxide in order to enhance penetration of 5-aminolevulinic acid (20% in cream) to which the lesions were exposed for 3 h prior to exposure to light. At examination 12-26 months (mean 17 months) after treatment 113 lesions (95%) were still in complete response. Six lesions (5%) had recurred, located on the face, scalp and ear. The cosmetic outcome was evaluated as excellent to good in 91%. Microscopic examination of biopsies taken from healed areas in 7 patients did not reveal any sign of damage in 5 and only minor alterations in 2.

Administration, Topical↗
PubMed1999

Skin scrape cytology in the diagnosis of nodular basal cell carcinoma for treatment by photodynamic therapy.

Photodynamic therapy is a new mode of cancer treatment with promising results for basal cell carcinoma. The current study aims to investigate the accuracy of skin scrape cytology in the diagnosis of basal cell carcinoma as an integrated part of the treatment procedure. A total of 107 nodular basal cell carcinomas of the skin from 90 patients were examined and cytological and histological diagnoses were compared. Compared with histopathology, cytopathology gave 3 false benign results (2.8%) and no false malignant diagnoses. Three lesions were benign by both methods. We conclude that basal cell carcinoma is reliably diagnosed with both techniques. However, cytology is simpler and faster, allowing treatment to be instituted shortly after the first consultation.

Basal Cell Carcinoma↗
PubMed1998

Nonrandom numerical chromosome abnormalities in basal cell carcinomas.

Clonal chromosome abnormalities were found in 22 of 23 short-term cultured basal cell carcinomas (BCC) of the skin. The karyotypic abnormalities were nonrandom and in several cases included evidence of clonal evolution. Especially in cultures showing an epithelial growth pattern, simple numerical changes, most commonly +18, +9, +20, +7, and +5, predominated and presumably constitute pathogenetically important aberrations present in the neoplastic parenchyma. Also, several structural rearrangements of chromosome arm 9q were seen, which may be of particular interest against the background that a gene for familial BCC (Gorlin syndrome), the PTCH gene, maps to this region. Finally, most of the clonal aberrations detected in predominantly fibroblast-like cultures are likely to reflect changes acquired by cells of the tumor stroma, which raises the question whether mutations also of this tumor component may play a pathogenetic role in BCC development.

Adult↗
PubMed1997

5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges.

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 protoprophyrin 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.

Aminolevulinic Acid↗
PubMed1997

The reciprocal translocation t(9;16)(q22;p13) is a primary chromosome abnormality in basal cell carcinomas.

The reciprocal translocation t(9;16)(q22;p13) was identified in three short-term cultured basal cell carcinomas (BCCs). The t(9;16) was the sole anomaly in one clone in two tumors and was accompanied by a second change that also affected the long arm of chromosome 9 in the third. In addition, other cytogenetically unrelated abnormal clones were also found in all three BCCs. The identification of t(9;16)(q22;p13) as a primary chromosomal abnormality in a subset of BCCs (we found it in 3 of 22 tumors) is especially intriguing against the background that the PTCH gene, which when mutated in the germ line presumably gives rise to the autosomal dominant basal cell nevus or Gorlin's syndrome, maps to chromosome band 9q22. None of the genes rearranged in the BCC-specific t(9;16)(q22;p13) translocation have been identified, but we hypothesize that the translocation represents the cytogenetic corollary of a tumorigenic recombination of PTCH with an as yet unknown gene in 16p13. If so, this would be the first time that a tumor suppressor gene causally involved in a hereditary cancer is shown to be frequently rearranged through a specific translocation in sporadic carcinomas of the same type.

Aged↗
PubMed1995

Distribution of 5-aminolevulinic acid-induced porphyrins in noduloulcerative basal cell carcinoma.

Microscopic fluorescence photometry incorporating a light-sensitive thermo-electrically cooled charge-coupled device (CCD) camera was employed to investigate the fluorescence distribution of 5-aminolevulinic acid (ALA)-induced porphyrins in 22 patients with a total number of 52 noduloulcerative basal cell carcinomas (BCC) after topical ALA application with or without dimethylsulfoxide (DMSO)/ethylenediaminetetraacetic acid (EDTA) or after intravenous administration of ALA. Both localization patterns and amounts of ALA-induced porphyrins in the BCC were studied. The ALA-induced porphyrins were localized only in the superficial layers of the noduloulcerative BCC lesions after topical application of 20% ALA alone for 3 h. However, both the penetration of ALA into deep lesions and the production of the ALA-induced porphyrin fluorescence were increased after topical administration of 20% ALA and 20% DMSO/4% EDTA for 3 h. Prior treatment with 99% DMSO for 15 min further enhanced the ALA penetration into the BCC lesions after topical application of the ALA/DMSO/EDTA mixture and produced more ALA-induced porphyrins by a factor of about three compared with those treated with ALA alone. The penetration of ALA into the deep BCC lesions could also be increased by prolonging the time of topical application of 20% ALA/4% EDTA to 29-48 h (without DMSO). Intravenous injection of ALA led to a more homogeneous distribution of the ALA-derived porphyrins in the whole noduloulcerative BCC lesions.

Adult↗
PubMed1994

Multiple glove powder granulomas masquerading as peritoneal carcinomatosis.

BACKGROUND: The occurrence of glove powder granulomas in peritoneal nodules presumed to represent carcinomatosis has not gained widespread attention and remains a challenging clinical problem even for the experienced surgeon. STUDY DESIGN: During the past four years, we have registered ten cases of multiple glove powder granulomas, believed by the surgeon to represent tumor dissemination, but diagnosed by the pathologist as glove powder granules with the typical Maltese cross pattern when viewed under polarized light. RESULTS: Patients were referred with the presumptive diagnosis of intra-abdominal malignant disease and all had undergone at least one previous laparotomy during the past few years at a hospital that used powdered gloves. The unsuspected perioperative finding of multiple peritoneal nodules was presumed to represent carcinomatosis and resulted in the surgeon erroneously cancelling the operation in one case. In six other cases, the results of perioperative frozen sections caused the surgeon to change strategy and perform the planned procedure. Three patients had starch powder peritonitis postoperatively and one of them had a fatal pulmonary embolus. In two patients, the starch powder reaction was associated with the occurrence of true carcinomatosis and one patient later had recurrence of hepatic metastases. After a mean follow-up period of 17 months, six patients are alive with no signs of disseminated malignancy. CONCLUSIONS: Based on this information, we recommend routine pathologic documentation of all peritoneal nodules appearing to be tumor dissemination. If the results influence the surgical procedure, frozen sections should always be performed. To minimize the risk of powder-induced complications, the use of particle-free gloves is strongly recommended.

Adult↗
PubMed1992

Distribution and photosensitizing efficiency of porphyrins induced by application of exogenous 5-aminolevulinic acid in mice bearing mammary carcinoma.

By means of a chemical extraction procedure and confocal laser scanning microscopy, we investigated the kinetic patterns of uptake and biolocalization of 5-aminolevulinic acid (ALA)-induced porphyrins in s.c. transplanted tumors, adjacent normal skin and muscle, and liver of mice bearing mammary carcinoma, after i.p. injection of 250 mg/kg ALA or topical application of ALA (20% in an oil-in-water emulsion). Furthermore, we evaluated the tumor responses after either i.p. injection or topical application of 5-ALA followed by laser irradiation (632 nm, 150 mW/cm2, 25 min) by measuring the treated tumor regression/regrowth time and by light and electron microscopy. Strong fluorescence of ALA-induced porphyrins was detected in the tumor, skin and liver tissues, while little fluorescence was seen in the adjacent muscle tissue. Moreover, the highest amounts of ALA-induced porphyrins in the tumor and skin tissues were found 1 hr after i.p. injection, whereas the amounts of the porphyrins in both tissues increased with increasing time after topical application of ALA. The fluorescence of the porphyrins was localized in several components of the skin tissue (epidermis, hair follicles and their associated sebaceous glands). Furthermore, the fluorescence was diffusely distributed in the s.c. transplanted tumor tissue. Little could be observed under a confocal laser scan microscope (CLSM) in the muscle tissue. The uptake and biolocalization data correlate well with the results of PCT efficiency of the same tumor model with ALA-induced porphyrins. Light and electron microscopy showed that the mitochondria of the tumor cells and of the endothelial cells and the basal lamina of vascular walls beneath the endothelium in the tumor tissue were initially extensively destroyed after PCT with ALA-induced porphyrins. Thereafter, diffuse degeneration followed by local and/or diffuse severe necrosis of the tumor cells was found. This may be due mainly to the initial damage to mitochondria in the cancerous and endothelial cells and also to the destruction of the vascular wall in the tumor tissue.

Aminolevulinic Acid↗