chlorophyll-a and Skin-Neoplasms

Photodynamic therapy (PDT) is a promising strategy for treating cancer. PDT involves three components: a photosensitizer (PS) drug, a specific wavelength of drug-activating light, and oxygen. A challenge in PDT is the unknown biodistribution of the PS in the target tissue. In this preliminary study, we report the development of a new approach to image in three dimensions the PS biodistribution in a noninvasive and fast manner.. A mesoscopic fluorescence tomography imaging platform was used to image noninvasively the biodistribution of 2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide-a (HPPH) in preclinical skin cancer models. Seven tumors were imaged and optical reconstructions were compared to nonconcurrent ultrasound data.. Successful imaging of the HPPH biodistribution was achieved on seven skin cancer tumors in preclinical models with a typical acquisition time of 1 minute. Two-dimensional fluorescence signals and estimated three-dimensional PS distributions were located within the lesions. However, HPPH distribution was highly heterogeneous with the tumors. Moreover, HPPH distribution volume and tumor volume as estimated by ultrasound did not match.. The results of this proof-of-concept study demonstrate the potential of MFMT to image rapidly the HPPH three-dimensional biodistribution in skin cancers. In addition, these preliminary data indicate that the PS biodistribution in skin cancer tumors is heterogeneous and does not match anatomical data. Mesoscopic fluorescence molecular tomography, by imaging fluorescence signals over large areas with high spatial sampling and at fast acquisition speeds, may be a new imaging modality of choice for planning and optimizing of PDT treatment.

Topics: Administration, Topical; Animals; Carcinoma, Basal Cell; Chlorophyll; Dermoscopy; Imaging, Three-Dimensional; Mice; Mice, Transgenic; Microscopy, Fluorescence; Photosensitizing Agents; Reproducibility of Results; Sensitivity and Specificity; Skin Absorption; Skin Neoplasms; Spectrometry, Fluorescence; Tissue Distribution; Tomography, Optical

2-[1-Hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), a second-generation photosensitizer, is employed in photodynamic therapy (PDT) for the treatment of various malignant lesions. PDT is a drug-device combined targeted treatment, and the clinical responses depend to a large extent on the photosensitizer distribution in target tissues and light exposure. In the present study, we aimed to give some suggestion for the development of HPPH-PDT from the perspective of photosensitizer biodistribution. For the first time, a PBPK model of HPPH was developed, which adequately described HPPH concentration-time profiles in rats plasma and various tissues. The rat PBPK model was further extrapolated to simulate the HPPH disposition in mouse and human. The simulated HPPH human serum concentrations yield a satisfactory agreement with observations at multiple dosing levels. It turned out that overweight may have a significant influence on HPPH exposure in human. Model simulated concentration-time profiles in human target tissues were also obtained. The appropriate time window to conduct light exposure for the treatment of digestive cancer and skin cancer could be 24-48 h and 48-96 h post-dose, respectively. Model simulations can explain the relevant clinical responses to some extent. The incorporation of the PBPK model into PDT could provide the photosensitizer concentrations not only in blood but also in target tissues, which may accelerate the development of this kind of treatment.

Topics: Animals; Chlorophyll; Female; Humans; Male; Mice; Photochemotherapy; Photosensitizing Agents; Rats; Rats, Sprague-Dawley; Skin Neoplasms; Tissue Distribution

"Radachlorin"(®), also known in the EU as Bremachlorin, a composition of 3 chlorophyll a derivatives in an aqueous solution, was introduced into the Russian Pharmacopoeia. Its GMP (Good Manufacturing Practice) facility based manufacturing method was patented. Laboratory experiments and clinical phase I were performed. Protocols were designed for PDT of basal cell carcinoma of the skin to result in GCP (Good Clinical Practice)-conformed randomized phase II clinical studies. "Radachlorin"(®) solution for intravenous infusions 0.35% 10mL in the doses of 0.5-0.6 and 1.0-1.2mg/kg and a gel for topical application 0.1% 25g in the dose of 0.1g/cm(2) were photoactivated by 2.5W 662nm semiconductor laser "LAKHTA-MILON(®)" (St. Petersburg, Russia) in light doses of 200, 300 (solution), 400, 600, 800 (gel) J/cm(2). Safety study showed no side effects and a good tolerability of "Radachlorin"(®) by patients. There was no normal skin/subdermal tissue damage after both laser and sun light exposure. The main part (98%) of the drug was excreted or metabolized in the first 48h. Drug administration at a dose of 1.0-1.2mg/kg and irradiation at 3h with 662±3nm light at a dose of 300J/cm(2) (solution) and 4 PDT sessions at an interval of 1 week with 3h gel exposure, followed by 400J/cm(2) light exposure (gel) were found to be the optimal treatment regimes. Having successfully passed clinical trials, "Radachlorin"(®) achieved marketing authorization in Russia in 2009 and a conditional approval in South Korea in 2008. It is a candidate for phase III clinical trials in the EC and may be commercialized as a prospective second-generation photosensitizer.

Topics: Carcinoma, Basal Cell; Chlorophyll; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Photochemotherapy; Photosensitizing Agents; Porphyrins; Skin Neoplasms

Constantin A. (Tino) Rebeiz, a pioneer in the field of chlorophyll biosynthesis, and a longtime member of the University of Illinois community of plant biologists, passed away on July 25, 2019. He came to the USA at a time that was difficult for members of minority groups to be in academia. However, his passion for the complexity of the biochemical origin of chlorophylls drove a career in basic sciences which extended into applied areas of environmentally friendly pesticides and treatment for skin cancer. He was a philanthropist; in retirement, he founded the Rebeiz Foundation for Basic Research which recognized excellence and lifetime achievements of selected top scientists in the general area of photosynthesis research. His life history, scientific breakthroughs, and community service hold important lessons for the field.

Topics: Achievement; Aminolevulinic Acid; Chlorophyll; History, 20th Century; Humans; Pesticides; Photosynthesis; Skin Neoplasms

Development of multifunctional biodegradable nanomaterials to encapsulate hydrophobic drugs and their triggered release in cancer theranostics is a challenge. In the current study, we report the encapsulation of potent anticancer - chlorophyll rich biomolecular fraction from the plant Anthocephalus cadamba into a polymeric nanosystem. The biomolecular fraction was combined with an NIR dye IR-780 to make it photo-thermally active. It was evaluated for its combinatorial (biomolecular extract and photothermal mediated) synergistic cytotoxicity in skin cancer cells. The inherent fluorescence of chlorophyll in the fraction was deployed to understand the cellular uptake and drug release. Cellular uptake of hydrophobic CFAc was enhanced with the aid of nanoformulation. It was observed that photo stability of IR-780 improved when incorporated with CFAc in polymeric nanosystem, which resulted in enhanced photothermal transduction efficiency. The combinational approach exhibited synergistic cytotoxicity which can be applied for skin cancer theranostics.

Topics: Animals; Cell Line, Tumor; Chlorophyll; Drug Carriers; Hyperthermia, Induced; Mice; Nanoparticles; Photochemotherapy; Rubiaceae; Skin Neoplasms; Theranostic Nanomedicine

Pheophorbide a (Pa), a chlorophyll derivative, is a photosensitizer that can induce significant antitumor effects in several types of tumor cells. The present study investigated the mechanism of Pa-mediated photodynamic therapy (Pa-PDT) in the human skin cancer cell lines A431 and G361. PDT significantly inhibited the cell growth in a Pa-concentration-dependent manner. We observed increased expression of Beclin-1, LC3B and ATG5, which are markers of autophagy, after PDT treatment in A431 cells but not in G361 cells. In G361 cells, Pa-PDT strongly induced PARP cleavage and subsequent apoptosis, which was confirmed using Annexin V/Propidium iodide double staining. Pa-PDT predominantly exhibited its antitumor effects via activation of ERK1/2 and p38 in A431 and G361 cells, respectively. An in vivo study using the CAM xenograft model demonstrated that Pa-PDT strongly induced autophagy and apoptosis in A431-transplanted tumors and/or apoptosis in G361-transplanted tumors. These results may provide a basis for understanding the underlying mechanisms of Pa-PDT and for developing Pa-PDT as a therapy for skin cancer.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Autophagy-Related Protein 5; Beclin-1; Cell Line, Tumor; Cell Proliferation; Chlorophyll; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Humans; MAP Kinase Signaling System; Membrane Potential, Mitochondrial; Membrane Proteins; Mice; Microtubule-Associated Proteins; p38 Mitogen-Activated Protein Kinases; Photochemotherapy; Photosensitizing Agents; Poly(ADP-ribose) Polymerases; Skin Neoplasms; Xenograft Model Antitumor Assays

Lung adenocarcinoma is a leading human malignancy with fatal prognosis. Ninety percent of the deaths, however, are caused by metastases. The model of subcutaneous tumor xenograft in nude mice was adopted to study the growth of control and photodynamically treated tumors derived from the human A549 lung adenocarcinoma cell line. As a side-result of the primary studies, observations on the metastasis of these tumors to the murine lungs were collected, and reported in the present paper. The metastasizing primary tumors were drained by a prominent number of lymphatic vessels. The metastatic tissue revealed the morphology of well-differentiated or trans-differentiated adenocarcinoma. Further histological and histochemical analyses demonstrated the presence of golden-brown granules in the metastatic tissue, similar to these found in the tumor tissue. In contrast to the primary tumors, the electron paramagnetic resonance spectroscopy revealed no nitric oxide - hemoglobin complexes (a source of intense paramagnetic signals), in the metastases. No metastases were found in other murine organs; however, white infarctions were identified in a single liver. Taken together, the A549-derived tumors growing subcutaneously in nude mice can metastasize and grow on site in the pulmonary tissue. Thus, they can represent an alternative for the model of induced metastatic nodule formation, following intravenous administration of the cancerous cells.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Animals; Cell Line, Tumor; Chlorophyll; Electron Spin Resonance Spectroscopy; Humans; Injections, Subcutaneous; Light; Liver Neoplasms; Lung Neoplasms; Male; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Photosensitizing Agents; Skin Neoplasms; Transplantation, Heterologous

Cell recurrence in cancer photodynamic therapy (PDT) is an important issue that is poorly understood. It is becoming clear that nitric oxide (NO) is a modulator of PDT. By acting on the NF-κB/Snail/RKIP survival/anti-apoptotic loop, NO can either stimulate or inhibit apoptosis. We found that pheophorbide a/PDT (Pba/PDT) induces the release of NO in B78-H1 murine amelanotic melanoma cells in a concentration-dependent manner. Low-dose PDT induces low NO levels by stimulating the anti-apoptotic nature of the above loop, whereas high-dose PDT stimulates high NO levels inhibiting the loop and activating apoptosis. When B78-H1 cells are treated with low-dose Pba/PDT and DETA/NO, an NO-donor, intracellular NO increases and cell growth is inhibited according to scratch-wound and clonogenic assays. Western blot analyses showed that the combined treatment reduces the expression of the anti-apoptotic NF-κB and Snail gene products and increases the expression of the pro-apoptotic RKIP gene product. The combined effect of Pba and DETA/NO was also tested in C57BL/6 mice bearing a syngeneic B78-H1 melanoma. We used pegylated Pba (mPEG-Pba) due to its better pharmacokinetics compared to free Pba. mPEG-Pba (30 mg/Kg) and DETA/NO (0.4 mg/Kg) were i.p. injected either as a single molecule or in combination. After photoactivation at 660 nM (fluence of 193 J/cm(2)), the combined treatment delays tumor growth more efficiently than each individual treatment (p<0.05). Taken together, our results showed that the efficacy of PDT is strengthened when the photosensitizer is used in combination with an NO donor.

Topics: Animals; Cell Line, Tumor; Chlorophyll; Female; Flow Cytometry; Melanoma, Amelanotic; Mice; Mice, Inbred C57BL; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Nitroso Compounds; Photochemotherapy; Photosensitizing Agents; Skin Neoplasms; Wound Healing

Photodynamic therapy (PDT) is a therapeutic modality whose efficacy depends on several factors including type of photosensitizer, light fluence and cellular response. Cell recurrence is one of the problems still unsolved in PDT. In this work we found that in B78-H1 murine amelanotic melanoma cells there is a correlation between cell recurrence and the NF-κB/Snail/RKIP loop.. Proliferation and migration of surviving cells were analyzed by MTT and wound-scratch assays. The levels of ROS/NO in B78-H1 melanoma cells treated with pheophorbide a (Pba) and light (Pba/PDT) were measured by FACS, while expression of NF-κB, Snail and RKIP were determined by Western blots. The mechanism of cell death was investigated by caspase and microscopy assays.. Our data show that after a low-dose Pba/PDT treatment, B78-H1 cells are able to recover. This correlates with a low level of NO production, which blocks apoptosis via NF-κB pathway. Western blot analyses showed that a low-dose Pba/PDT increases the expression of NF-κB and anti-apoptotic Snail, but reduces the expression of pro-apoptotic RKIP. The role played by NF-κB in the modulation of Snail and RKIP was investigated using DHMEQ: a NF-κB inhibitor which behaves as NO donor. DHMEQ caused a decrease of Snail and an increase of RKIP expression. When B78-H1 cells were treated with a low dose Pba/PDT and DHMEQ, the NO level strongly increased, with the result that Snail was down-regulated and RKIP was upregulated, as observed with a high-dose Pba/PDT.. One major problem in PDT is the cellular rescue occurring in tissue regions receiving a low-dose PDT. To minimize this problem and sensitize cancer cells to PDT we propose a combined treatment in which the photosensitizer is delivered with a donor of NO acting on the NF-κB/Snail/RKIP loop.

Topics: Animals; Apoptosis; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chlorophyll; Dose-Response Relationship, Drug; Melanoma, Amelanotic; Mice; NF-kappa B; Nitric Oxide; Phosphatidylethanolamine Binding Protein; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Skin Neoplasms; Snail Family Transcription Factors; Transcription Factors

Photodynamic therapy is an effective and often curative treatment for certain solid tumors. The porphyrin-based photosensitizer Photofrin, the only Food and Drug Administration-approved drug for this therapy, suffers from certain disadvantages: its complex chemical nature; retention by skin (leading to protracted cutaneous photosensitivity); and less than optimal photophysical properties. In this study, we examine the population pharmacokinetics and cutaneous phototoxicity of 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), a chlorin-type photosensitizer with more favorable photophysical properties. HPPH plasma concentration-time data were obtained in 25 patients enrolled in Phase I-II clinical trials for the treatment of partially obstructive esophageal carcinoma, high-grade dysplasia associated with Barrett's esophagus, carcinoma of the lung, or multiple basal cell carcinomas. Doses of 3, 4, 5, or 6 mg/m(2) were administered as 1-h i.v. infusions. The pharmacokinetic data for each patient were fitted with a standard two-compartment (biexponential) model with continuous infusion. The model fitting approach was iteratively reweighted nonlinear regression, with weights equal to the reciprocal of the square of the predicted HPPH plasma concentrations. The complete set of data for all 25 patients was then fitted simultaneously with nonlinear mixed effects modeling. Cutaneous phototoxicity responses were determined, as a function of time after HPPH infusion, following exposure to various doses of light from a solar simulator. The estimates of the population mean (variance) for each parameter were as follows: volume of distribution (V(C)), 2.40 liters/m(2) (0.259); steady-state volume (V(SS)), 9.58 liters/m(2) (11.6); systemic clearance (CL), 0.0296 liter/h/m(2) (0.000094); and distributional clearance (CL(D)), 0.144 liter/h/m(2) (0.00166). These parameters were independent of dose. Clearance increased with age. A relative error model was used for the difference in the raw and fitted data, and the overall coefficient of variation estimate across all of the data was 14.5%. The estimated mean population alpha and beta half-lives (95% confidence interval) were 7.77 h (3.46-17.6 h) and 596 h (120-2951 h), respectively. High-performance liquid chromatography analysis of serum showed no circulating HPPH metabolites, and in vitro incubation of HPPH with human liver microsomal preparations resulted in no metabolite or glucuronic acid-HPPH conjugate production.

Topics: Adult; Aged; Aged, 80 and over; Barrett Esophagus; Blood Proteins; Carcinoma, Basal Cell; Chlorophyll; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Esophageal Neoplasms; Humans; Lung Neoplasms; Middle Aged; Neoplasms; Photochemotherapy; Photosensitizing Agents; Skin; Skin Neoplasms

We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide-a derivative PH-1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX-70, a commonly used sonosensitizer. Mice were injected with either PH-1126 or ATX-70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX-70) or 36 hr (PH-1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX-70; 44J/cm2 of 650 nm for PH-1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH-1126 or ATX-70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92-98%) (additive effect) as compared to either single treatment (27-77%). The combination using PH-1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT-treated mice (> 120 days) was significantly greater than that in single treatment groups (77-95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2-3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non-superficial or nodular tumors.

Topics: Animals; Carcinoma, Squamous Cell; Chlorophyll; Combined Modality Therapy; Disease Models, Animal; Female; Gallium; Male; Mice; Mice, Inbred C3H; Photochemotherapy; Photosensitizing Agents; Porphyrins; Random Allocation; Skin Neoplasms; Survival Analysis; Ultrasonic Therapy

Potent antigenotoxic and anti-tumor promoting activities of chlorophyll a from green tea (camellia sinensis) have been shown using in vitro cell culture experiments (Okai Y. et al. (1996) Mutation Res., 370, 11-17). In the present study, the authors analyzed in vivo effects of chlorophyll a and b from green tea on tumor promotion in mouse skin in the following ways. 1. When chlorophyll a and b from green tea were applied before each treatment by a tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on BALB/c mouse skin initiated by 7, 12-dimethylbenz [a] an-thracene (DMBA), they caused significant suppression in a dose-dependent manner against BALB/c mouse skin tumorigenesis. 2. Chlorophyll a and b showed significant suppressive effects against TPA-induced inflammatory reaction such as edema formation in BALB/c mouse ear skin in a dose-dependent fashion. These results suggest that chlorophyll a and b possess potent suppressive activities against tumor promotion in mouse skin.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Chlorophyll; Chlorophyll A; Edema; Mice; Mice, Inbred BALB C; Pigments, Biological; Skin Neoplasms; Tea; Tetradecanoylphorbol Acetate

Photodynamic therapy has been shown to be an effective treatment modality for surface-oriented neoplasms of the skin, respiratory, gastrointestinal, and urogenital systems. The purpose of this study was to assess the safety and efficacy of photodynamic therapy using a new photosensitizer in the treatment of squamous cell carcinomas of the feline facial skin.. Cats with naturally occurring squamous cell carcinomas of the facial skin were entered into the study. Tumors were staged using a modification of the World Health Organization (WHO) system for classification of feline tumors of epidermal origin. Photodynamic therapy was delivered to the tumors using an argon-pumped dye laser 24 hours after the administration of the photosensitizer pyropheophorbide-alpha-hexyl-ether (HPPH-23). Following treatment, tumors were evaluated for complete response rates and local control durations.. Fifteen tumors were staged T1a (< 1.5 cm diameter, noninvasive), 18 T1b (< 1.5 cm, invasive), and 28 T2B (> 1.5 cm, invasive). Complete response rates as well as local control durations were significantly (P < 0.05) related to stage. Complete response was achieved in 100% of T1a tumors, 56% of T1b tumors, and 18% of T2b tumors. One-year local control rates were 100% for T1a tumors and 53% for T1b tumors; overall 1-year local control rate for all treated tumors was 62%. Clinical, hematological, and biochemical evidence of toxicity was not seen in any cat following drug administration. However, morbidity was observed following treatment of large, invasive tumors of the nasal plane.. Photodynamic therapy with the photosensitizer HPPH-23 was safe and effective in treating early stage squamous cell carcinomas of the feline nasal plane and facial skin. However, toxicity was encountered following treatment of large neoplasms.

Topics: Animals; Carcinoma, Squamous Cell; Cats; Chlorophyll; Edema; Inflammation; Opportunistic Infections; Photochemotherapy; Photosensitizing Agents; Skin Neoplasms

Anti-tumor-promoting activity of pheophorbide a (PPBa) a chlorophyll-related compound, was examined in a two-stage carcinogenesis experiment in ICR mouse skin by 7,12-dimethylbenz[a] anthracene (DMBA, 0.19 mumol) and 12-O-tetradecanoylphorbol-13-acetate (TPA, 1.6 nmol). Topical application of PPBa (160 nmol) markedly reduced the average number of tumors per mouse and the ratio of tumor-bearing mice (inhibitory ratio: IR = 56%, P < 0.01 and 31%, P < 0.005, respectively). PPBa exhibited potent anti-inflammatory activity in ICR mouse ears and moderate inhibitory activity toward TPA-induced superoxide (O2-) generation in differentiated HL-60 cells. While CuPPBa, a synthetic copper complex of PPBa, exhibited higher anti-inflammatory activity than that of indomethacin, it showed little antioxidative effect against formation of lipid hydroperoxides (LOOHs) and malondialdehyde (MDA), suggesting that the antioxidative effect of PPBa might not be important for anti-inflammatory activity. These results imply that the active mechanism of PPBa for anti-tumor promotion might be partly involved in inhibition of TPA-induced inflammatory responses by suppressing leukocyte activation.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Carcinogens; Chlorophyll; Drug Screening Assays, Antitumor; Female; Mice; Mice, Inbred ICR; Neoplasms, Experimental; Skin Neoplasms; Tetradecanoylphorbol Acetate

Liposomes are a potential system for more selective delivery of photosensitizers (PS) to tumors. Pheophorbides are one series of new PS under investigation for use in photodynamic therapy. The pharmacokinetics, anti-tumor response and normal tissue effects of methylpheophorbide-a-(hexyl-ether) (MPH) associated with negatively charged phospholipid vesicles composed of high and low transition temperature lipids were determined in mice. In some preparations monosialoganglioside, which is known to impart long circulation time to liposomes was also included. Normally water-insoluble MPH could be quantitatively incorporated in multilamellar liposomes up to at least 20 mol MPH/mol lipid% for most liposome compositions and sonicated to form clear suspensions. Evidence from electron microscopy and entrapment of aqueous space markers indicated that the particles formed by sonication were not standard liposomes. Anti-tumor responses to light treatment (135 J/cm2, 665 nm argon-dye laser) 24 h after MPH (0.4 mumol/kg) administration were slightly but significantly greater (P < 0.05) for lipid associated MPH compared to MPH solubilized in Tween 80. There were no major differences in tumor uptake and tumor cell photosensitization between lipid or Tween 80 formulations of MPH, whereas, dependent on lipid composition and time after MPH administration, the doses of light required to cause occlusive vascular damage were increased for the lipid formulations. Pharmacokinetic studies showed rapid dissociation between lipids and MPH in vivo. Lipid formulations are useful for solubilizing MPH and may improve the therapeutic effects of this PS.

Topics: Animals; Chlorophyll; Dose-Response Relationship, Radiation; Drug Carriers; Female; Fibrosarcoma; Liposomes; Mice; Mice, Inbred C3H; Microcirculation; Photochemotherapy; Photosensitizing Agents; Polysorbates; Skin; Skin Neoplasms; Tissue Distribution

The in vivo photosensitizing efficacy of chlorophyll derivatives (CpD), which had been developed as a new photosensitizer, was compared with that of hematoporphyrin derivatives (HpD). A murine tumor model implanted subcutaneously with S-180 cells on the abdomen was used. The CpD or HpD was administered by intratumoral injection, and light of appropriate wavelength was irradiated on the tumor areas for 10 minutes at 1h and 24h or 24h and 48h after the injection of photosensitizer. When CpD was injected, the early irradiation group (1h and 24h) showed a 100% tumor cure rate; however, the late irradiation group (24h and 48h) showed a 60% tumor cure rate (p less than 0.01). This showed that the early irradiation with light after injection of CpD was an important factor for obtaining better results. With HpD, there was no difference in tumor cure rate between early (1h and 24h, 80%) and late irradiation (24h and 48h, 80%) groups. Thus, in early irradiation groups, the tumor cure rate using CpD (100%) was superior to that of HpD (80%) (p less than 0.05). However, in late irradiation groups, the tumor cure rate using CpD (60%) was inferior to that of HpD (80%), but this difference was not statistically significant (p greater than 0.1). Pathologic sections of these tumors were made before treatment and 48h and 3 weeks after treatment. These showed geographic necrosis at 48h after treatment and no viable tumor tissue at 3 weeks after treatment. Our results showed that CpD was as effective as HpD as a photosensitizer for in vivo photodynamic therapy.

Topics: Abdomen; Animals; Chlorophyll; Mice; Mice, Inbred ICR; Photochemotherapy; Sarcoma, Experimental; Skin Neoplasms

Topics: Carcinoma; Carcinoma, Basal Cell; Chlorophyll; Enzymes; Humans; Skin Neoplasms