chlorophyll-a has been researched along with Lung-Neoplasms* in 22 studies
1 review(s) available for chlorophyll-a and Lung-Neoplasms
1 trial(s) available for chlorophyll-a and Lung-Neoplasms
| Article | Year |
|---|---|
A Phase I Study of Light Dose for Photodynamic Therapy Using 2-[1-Hexyloxyethyl]-2 Devinyl Pyropheophorbide-a for the Treatment of Non-Small Cell Carcinoma In Situ or Non-Small Cell Microinvasive Bronchogenic Carcinoma: A Dose Ranging Study.
We report a phase I trial of photodynamic therapy (PDT) of carcinoma in situ (CIS) and microinvasive cancer (MIC) of the central airways with the photosensitizer (PS) 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH). HPPH has the advantage of minimal general phototoxicity over the commonly used photosensitizer porfimer sodium (Photofrin; Pinnacle Biologics, Chicago, IL).. The objectives of this study were (1) to determine the maximally tolerated light dose at a fixed photosensitizer dose and (2) to gain initial insight into the effectiveness of this treatment approach. Seventeen patients with 21 CIS/MIC lesions were treated with HPPH with light dose escalation starting from 75 J/cm2 and increasing to 85, 95,125, and 150 J/cm2 respectively. Follow-up bronchoscopy for response assessment was performed at 1 and 6 months, respectively.. The rate of pathological complete response (CR) was 82.4% (14 of 17 evaluable lesions; 14 patients) at 1 month and 72.7% (8/11 evaluable lesions; 8 patients) at 6 months. Only four patients developed mild skin erythema. One of the three patients in the 150 J/cm2 light dose group experienced a serious adverse event. This patient had respiratory distress caused by mucus plugging, which precipitated cardiac ischemia. Two additional patients treated subsequently at this light dose had no adverse events. The sixth patient in this dose group was not recruited and the study was terminated because of delays in HPPH supply. However, given the observed serious adverse event, it is recommended that the light dose does not exceed 125 J/cm2.. PDT with HPPH can be safely used for the treatment of CIS/MIC of the airways, with potential effectiveness comparable to that reported for porfimer sodium in earlier studies. Topics: Aged; Aged, 80 and over; Carcinoma in Situ; Carcinoma, Bronchogenic; Carcinoma, Non-Small-Cell Lung; Chlorophyll; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents | 2016 |
20 other study(ies) available for chlorophyll-a and Lung-Neoplasms
| Article | Year |
|---|---|
Define the Two Molecular Subtypes of Epithelioid Malignant Pleural Mesothelioma.
Malignant pleural mesothelioma (MPM) is a fatal disease of respiratory system. Despite the availability of invasive biomarkers with promising results, there are still significant diagnostic and therapeutic challenges in the treatment of MPM. One of three main mesothelioma cell types, epithelioid mesothelioma makes up approximately 70% of all mesothelioma cases. Different observational findings are under process, but the molecular heterogeneity and pathogenesis of epithelioid malignant pleural mesothelioma (eMPM) are still not well understood. Through molecular analysis, expression profiling data were used to determine the possibility and optimal number of eMPM molecular subtypes. Next, clinicopathological characteristics and different molecular pathways of each subtype were analyzed to prospect the clinical applications and advanced mechanisms of eMPM. In this study, we identified two distinct epithelioid malignant pleural mesothelioma subtypes with distinct gene expression patterns. Subtype I eMPMs were involved in steroid hormone biosynthesis, porphyrin and chlorophyll metabolism, and drug metabolism, while subtype II eMPMs were involved in rational metabolism, tyrosine metabolism, and chemical carcinogenesis pathways. Additionally, we identified potential subtype-specific therapeutic targets, including CCNE1, EPHA3, RNF43, ROS1, and RSPO2 for subtype I and CDKN2A and RET for subtype II. Considering the need for potent diagnostic and therapeutic biomarkers for eMPM, we are anticipating that our findings will help both in exploring underlying mechanisms in the development of eMPM and in designing targeted therapy for eMPM. Topics: Chlorophyll; Hormones; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Porphyrins; Proto-Oncogene Proteins; Steroids; Tyrosine | 2022 |
Topics: Adult; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antigens, Surface; Antineoplastic Agents; Antioxidants; Antiviral Agents; Aporphines; Atherosclerosis; Benzoyl Peroxide; beta Catenin; Biofilms; Biomarkers; Brain; Cannabis; Carcinoma, Squamous Cell; Case-Control Studies; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Child; China; Chlorides; Chlorophyll; Cholesterol, LDL; Coinfection; Corylus; Cross-Sectional Studies; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Developmental Disabilities; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; Electroencephalography; Environmental Exposure; Enzyme Inhibitors; Epilepsy, Generalized; Ethnicity; Female; Fertilization in Vitro; Fluorescent Dyes; Follow-Up Studies; Forecasting; Glutamate Carboxypeptidase II; Glycine; Half-Life; Head and Neck Neoplasms; Health Communication; Heart Ventricles; Hepacivirus; Hepatitis C; Heterosexuality; HIV Infections; Humans; Hypercholesterolemia; Immunoassay; Inhalation Exposure; Isocitrate Dehydrogenase; Laryngeal Neoplasms; Ligands; Light; Lipopolysaccharide Receptors; Liver Cirrhosis; Lung; Lung Neoplasms; Magnetic Resonance Imaging, Cine; Male; Maternal Age; Mechanical Phenomena; Mice; Mice, Nude; Mice, SCID; Microglia; MicroRNAs; Microscopy, Fluorescence; Microsomes, Liver; Middle Aged; Minority Groups; Mitochondrial Membrane Transport Proteins; Models, Biological; Molecular Structure; Molecular Weight; Monte Carlo Method; Muscle Hypotonia; Mutagenesis, Site-Directed; Mutation, Missense; Natriuretic Peptide, Brain; Neoplasms; Nickel; Nitric Oxide; Optical Imaging; Oxides; Particle Size; Particulate Matter; PCSK9 Inhibitors; Peptide Fragments; Phenotype; Photochemotherapy; Photosensitizing Agents; Phytochemicals; Piper; Placenta Growth Factor; Plant Extracts; Plant Leaves; Plant Stems; Platinum; Point-of-Care Testing; Population Surveillance; Postpartum Period; Pregnancy; Pregnancy, Twin; Prevalence; Prospective Studies; Prostatic Neoplasms; Pseudomonas aeruginosa; Pyridines; Pyridones; Racial Groups; Rats; Respiratory Physiological Phenomena; Retrospective Studies; Risk Factors; RNA, Long Noncoding; Semiconductors; Sexual and Gender Minorities; Sexual Behavior; Social Media; Sodium; Solubility; Stereoisomerism; Stochastic Processes; Structure-Activity Relationship; Substance-Related Disorders; Sustained Virologic Response; Sweat; Temperature; Time Factors; Tissue Distribution; Titanium; Transplantation, Heterologous; Tumor Cells, Cultured; Tungsten; Tyramine; United States; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left; Veterans; Xenograft Model Antitumor Assays; Young Adult | 2021 |
Cell-specific Retention and Action of Pheophorbide-based Photosensitizers in Human Lung Cancer Cells.
This study determined in primary cultures of human lung cancer cells the cell specificity of chlorin-based photosensitizers. Epithelial cells (ECs) preferentially retained 3-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and related structural variants. Tumor-associated fibroblasts (Fb) differ from EC by a higher efflux rate of HPPH. Immunoblot analyses indicated dimerization of STAT3 as a reliable biomarker of the photoreaction. Compared to mitochondria/ER-localized photoreaction by HPPH, the photoreaction by lysosomally targeted HPPH-lactose showed a trend toward lower STAT3 cross-linking. Lethal consequence of the photoreaction differed between EC and Fb with the latter cells being more resistant. A survey of lung tumor cases indicated a large quantitative range by which EC retains HPPH. The specificity of HPPH retention defined in vitro could be confirmed in vivo in selected cases grown as xenografts. HPPH retention as a function of the tetrapyrrole structure was evaluated by altering side groups on the porphyrin macrocycle. The presence or absence of a carboxylic acid at position 17 Topics: Animals; Carcinoma, Non-Small-Cell Lung; Chlorophyll; Female; Humans; Lung Neoplasms; Male; Mice; Mice, SCID; Photochemotherapy; Photosensitizing Agents; Tumor Cells, Cultured; Xenograft Model Antitumor Assays | 2019 |
N-(2-hydroxypropyl)methacrylamide polymer conjugated pyropheophorbide-a, a promising tumor-targeted theranostic probe for photodynamic therapy and imaging.
Topics: Animals; Chlorophyll; Fluorescence; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Micelles; Particle Size; Permeability; Photochemotherapy; Photosensitizing Agents; Polymers; Polymethacrylic Acids; Theranostic Nanomedicine; Time Factors; Tissue Distribution | 2018 |
Structural and Epimeric Isomers of HPPH [3-Devinyl 3-{1-(1-hexyloxy) ethyl}pyropheophorbide-a]: Effects on Uptake and Photodynamic Therapy of Cancer.
The tetrapyrrole structure of porphyrins used as photosentizing agents is thought to determine uptake and retention by malignant epithelial cancer cells. To assess the contribution of the oxidized state of individual rings to these cellular processes, bacteriochlorophyll a was converted into the ring "D" reduced 3-devinyl-3-[1-(1-hexyloxy)ethyl]pyropheophorbide-a (HPPH) and the corresponding ring "B" reduced isomer (iso-HPPH). The carboxylic acid analogs of both ring "B" and ring "D" reduced isomers showed several-fold higher accumulation into the mitochondria and endoplasmic reticulum by primary culture of human lung and head and neck cancer cells than the corresponding methyl ester analogs that localize primarily to granular vesicles and to a lesser extent to mitochondria. However, long-term cellular retention of these compounds exhibited an inverse relationship with tumor cells generally retaining better the methyl-ester derivatives. In vivo distribution and tumor uptake was evaluated in the isogenic model of BALB/c mice bearing Colon26 tumors using the respective Topics: Animals; Cell Line, Tumor; Chlorophyll; Head and Neck Neoplasms; Humans; Isomerism; Lung Neoplasms; Mice; Mice, Inbred BALB C; Molecular Structure; Photochemotherapy; Photosensitizing Agents | 2017 |
Photodynamic therapy of human lung cancer xenografts in mice.
There is a need to develop novel therapies for non-small cell lung cancer (NSCLC). Photodynamic therapy has been used successfully for endobronchial palliation of NSCLC, and its role in early stages of disease is being explored. We hypothesized that a novel photosensitizer, PS1, would be more effective than the standard agent, porfimer sodium (Photofrin or PFII), in treating human lung cancer xenografts in mice.. Patient-derived NSCLC xenografts were established subcutaneously in severe combined immune deficiency mice. Two groups of five mice were injected with PS1 (3-[1'-m-iodobenzyloxy]ethyl-3-devinylpyropheophorbide-a), a chlorophyll-a derivative, or PFII (a purified version of hematoporphyrin derivative) and then treated with nonthermal laser light. Four mice were treated with laser light without photosensitizer and six mice received no treatment at all. All mice were then observed for tumor growth. The tumor growth end point, time-to-1000 mm(3), was evaluated using standard Kaplan-Meier methods and the log-rank test. Tumor hematoxylin and eosin and caspase 3 staining was done to evaluate necrosis and apoptosis.. The median time-to-1000 mm(3) was 12, 12, 26, and 52 d for the control, light only, PFII, and PS1 groups. There was a significant association between the tumor growth end point and treatment (P < 0.05). Hematoxylin and eosin staining revealed <1%, 0%, 67%, and 80% necrosis, and caspase 3 positivity was 2%, <1%, 17%, and 39%, respectively, in the same four groups.. The mice treated with PS1 exhibited a longer time for tumor regrowth and showed more tumor necrosis and apoptosis compared with the other treatment groups. Thus, the novel photosensitizer, PS1, was demonstrated to be more effective than porfimer sodium in this preclinical pilot study. Topics: Animals; Carcinoma, Non-Small-Cell Lung; Chlorophyll; Dihematoporphyrin Ether; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Mice; Mice, SCID; Neoplasm Transplantation; Photochemotherapy; Photosensitizing Agents; Pilot Projects; Transplantation, Heterologous; Treatment Outcome | 2016 |
Fluence Rate Differences in Photodynamic Therapy Efficacy and Activation of Epidermal Growth Factor Receptor after Treatment of the Tumor-Involved Murine Thoracic Cavity.
Photodynamic therapy (PDT) of the thoracic cavity can be performed in conjunction with surgery to treat cancers of the lung and its pleura. However, illumination of the cavity results in tissue exposure to a broad range of fluence rates. In a murine model of intrathoracic PDT, we studied the efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH; Photochlor(®))-mediated PDT in reducing the burden of non-small cell lung cancer for treatments performed at different incident fluence rates (75 versus 150 mW/cm). To better understand a role for growth factor signaling in disease progression after intrathoracic PDT, the expression and activation of epidermal growth factor receptor (EGFR) was evaluated in areas of post-treatment proliferation. The low fluence rate of 75 mW/cm produced the largest reductions in tumor burden. Bioluminescent imaging and histological staining for cell proliferation (anti-Ki-67) identified areas of disease progression at both fluence rates after PDT. However, increased EGFR activation in proliferative areas was detected only after treatment at the higher fluence rate of 150 mW/cm. These data suggest that fluence rate may affect the activation of survival factors, such as EGFR, and weaker activation at lower fluence rate could contribute to a smaller tumor burden after PDT at 75 mW/cm. Topics: Animals; Autoantigens; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Chlorophyll; ErbB Receptors; Female; Humans; Lung Neoplasms; Mice; Photochemotherapy; Proteasome Endopeptidase Complex | 2016 |
Photodynamic Therapy Mediated by Nontoxic Core-Shell Nanoparticles Synergizes with Immune Checkpoint Blockade To Elicit Antitumor Immunity and Antimetastatic Effect on Breast Cancer.
An effective, nontoxic, tumor-specific immunotherapy is the ultimate goal in the battle against cancer, especially the metastatic disease. Checkpoint blockade-based immunotherapies have been shown to be extraordinarily effective but benefit only the minority of patients whose tumors have been pre-infiltrated by T cells. Here, we show that Zn-pyrophosphate (ZnP) nanoparticles loaded with the photosensitizer pyrolipid (ZnP@pyro) can kill tumor cells upon irradiation with light directly by inducing apoptosis and/or necrosis and indirectly by disrupting tumor vasculature and increasing tumor immunogenicity. Furthermore, immunogenic ZnP@pyro photodynamic therapy (PDT) treatment sensitizes tumors to checkpoint inhibition mediated by a PD-L1 antibody, not only eradicating the primary 4T1 breast tumor but also significantly preventing metastasis to the lung. The abscopal effects on both 4T1 and TUBO bilateral syngeneic mouse models further demonstrate that ZnP@pyro PDT treatment combined with anti-PD-L1 results in the eradication of light-irradiated primary tumors and the complete inhibition of untreated distant tumors by generating a systemic tumor-specific cytotoxic T cell response. These findings indicate that nanoparticle-mediated PDT can potentiate the systemic efficacy of checkpoint blockade immunotherapies by activating the innate and adaptive immune systems in tumor microenvironment. Topics: Animals; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Chlorophyll; Combined Modality Therapy; Diphosphates; Humans; Immunotherapy; Light; Lipids; Lung Neoplasms; Mice; Nanoparticles; Necrosis; Neoplasm Metastasis; Photochemotherapy; Photosensitizing Agents; Zinc | 2016 |
Induction of p53-independent growth inhibition in lung carcinoma cell A549 by gypenosides.
The objectives of this study are to investigate antiproliferative effect and mechanisms of bioactive compounds from Gynostemma pentaphyllum (G. pentaphyllum) on lung carcinoma cell A549. Saponins, carotenoids and chlorophylls were extracted and fractionated by column chromatography, and were subjected to high-performance liquid chromatography-mass spectrometry analyses. The saponin fraction, which consisted mainly of gypenoside (Gyp) XXII and XXIII, rather than the carotenoid and chlorophyll ones, was effective in inhibiting A549 cell growth in a concentration- and a time-dependent manner as evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The estimated half maximal inhibitory concentration (IC50 ) of Gyp on A549 cells was 30.6 μg/ml. Gyp was further demonstrated to induce an apparent arrest of the A549 cell cycle at both the S phase and the G2/M phase, accompanied by a concentration- and a time-dependent increase in the proportions of both the early and late apoptotic cells. Furthermore, Gyp down-regulated cellular expression of cyclin A and B as well as BCL-2, while up-regulated the expression of BAX, DNA degradation factor 35 KD, poly [ADP-ribose] polymerase 1, p53, p21 and caspase-3. Nevertheless, both the treatment of a p53 inhibitor, pifithrin-α, and the small hairpin RNA-mediated p53 knockdown in the A549 cells did not alter the growth inhibition effect induced by Gyp. As a result, the cell cycle arrest and apoptosis of A549 cells induced by Gyp would most likely proceed through p53-independent pathway(s). Topics: Annexin A5; Apoptosis; Carotenoids; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Chlorophyll; Chromatography, High Pressure Liquid; Flow Cytometry; Gynostemma; Humans; Lung Neoplasms; Mass Spectrometry; Plant Extracts; Saponins; Tumor Suppressor Protein p53 | 2015 |
Effect of chirality on cellular uptake, imaging and photodynamic therapy of photosensitizers derived from chlorophyll-a.
We have previously shown that the (124)I-analog of methyl 3-(1'-m-iodobenzyloxy) ethyl-3-devinyl-pyropheophorbide-a derived as racemic mixture from chlorophyll-a can be used for PET (positron emission tomography)-imaging in animal tumor models. On the other hand, as a non-radioactive analog, it showed excellent fluorescence and photodynamic therapy (PDT) efficacy. Thus, a single agent in a mixture of radioactive ((124)I-) and non-radioactive ((127)I) material can be used for both dual-imaging and PDT of cancer. Before advancing to Phase I human clinical trials, we evaluated the activity of the individual isomers as well as the impact of a chiral center at position-3(1) in directing in vitro/in vivo cellular uptake, intracellular localization, epithelial tumor cell-specific retention, fluorescence/PET imaging, and photosensitizing ability. The results indicate that both isomers (racemates), either as methyl ester or carboxylic acid, were equally effective. However, the methyl ester analogs, due to subcellular deposition into vesicular structures, were preferentially retained. All derivatives containing carboxylic acid at the position-17(2) were noted to be substrate for the ABCG2 (a member of the ATP binding cassette transporters) protein explaining their low retention in lung tumor cells expressing this transporter. The compounds in which the chirality at position-3 has been substituted by a non-chiral functionality showed reduced cellular uptake, retention and lower PDT efficacy in mice bearing murine Colon26 tumors. Topics: Animals; Biological Transport; Carcinoma, Squamous Cell; Cell Line, Tumor; Chlorophyll; Chlorophyll A; Colonic Neoplasms; Epithelial Cells; Fibroblasts; Humans; Iodine Radioisotopes; Lung Neoplasms; Mice; Mice, Inbred BALB C; Molecular Imaging; Neoplasm Transplantation; Organ Specificity; Photochemotherapy; Photosensitizing Agents; Spirulina; Stereoisomerism; Tumor Burden | 2015 |
Pulmonary metastases of the A549-derived lung adenocarcinoma tumors growing in nude mice. A multiple case study.
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 | 2013 |
Photodynamic therapy of disseminated non-small cell lung carcinoma in a murine model.
Photodynamic therapy (PDT) of thoracic malignancies involving the pleural surfaces is an active area of clinical investigation. The present report aims to characterize a model for PDT of disseminated non-small cell lung carcinoma (NSCLC) grown orthotopically in nude mice, and to evaluate the effect of PDT on tumor and normal tissues.. H460 human NSCLC cells were injected percutaneously into the thoracic cavity of nude mice. HPPH-PDT (1 mg/kg, 24 hours) was performed via the interstitial delivery (150 mW/cm) of 661 nm light to the thoracic cavity at fluences of 25-200 J/cm.. H460 tumors exhibited exponential growth within the thoracic cavity consisting of diffuse, gross nodular disease within 9 days after intrathoracic injection. Tumor volume, measured by magnetic resonance imaging (MRI), was highly correlated with the aggregate tumor mass extracted from the corresponding animal. Intrathoracic PDT at fluences of ≥50 J/cm produced significant decreases in tumor burden as compared to untreated controls, however, mortality increased with rising fluence. Accordingly, 50 J/cm was selected for MRI studies to measure intra-animal PDT effects. Tumor distribution favored the ventral (vs. dorsal), caudal (vs. cranial), and right (vs. left) sides of the thoracic cavity by MRI; PDT did not change this spatial pattern despite an overall effect on tumor burden. Histopathology revealed edema and fibrin deposition within the pulmonary interstitium and alveoli of the PDT-treated thoracic cavity, as well as occasional evidence of vascular disruption. Prominent neutrophil infiltration with a concomitant decline in the lymphocyte compartment was also noted in the lung parenchyma within 24 hours after PDT.. HPPH-PDT of an orthotopic model of disseminated NSCLC is both feasible and effective using intracavitary light delivery. We establish this animal model, together with the treatment and monitoring approaches, as novel and valuable methods for the pre-clinical investigation of intrathoracic PDT of disseminated pleural malignancies. Topics: Animals; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Chlorophyll; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Magnetic Resonance Imaging; Mice; Mice, Nude; Photochemotherapy; Photosensitizing Agents; Tumor Burden | 2011 |
Changes in free amino acid, phenolic, chlorophyll, carotenoid, and glycoalkaloid contents in tomatoes during 11 stages of growth and inhibition of cervical and lung human cancer cells by green tomato extracts.
Tomato ( Solanum lycopersicum ) plants synthesize nutrients, pigments, and secondary metabolites that benefit nutrition and human health. The concentrations of these compounds are strongly influenced by the maturity of the tomato fruit on the vine. Widely consumed Korean tomatoes of the variety Doturakworld were analyzed for changes in the content of free amino acids, phenolic compounds, chlorophylls, carotenoids, and glycoalkaloids at 11 stages (S1-S11) of ripeness. The results show that (a) the total content (in mg/100 g of FW) of the free amino acids and other nitrogen-containing compounds in the extracts ranged from about 41 to 85 in the green tomato extracts S1-S7 and then increased to 251 (S9) in the red extracts, followed by a decrease to 124 in S11 red extracts; (b) the total initial concentration and composition of up to 12 phenolic compounds of approximately 2000 microg/100 g of FW varied throughout the ripening process, with the quantity decreasing and the number of individual compounds increasing in the red tomato; (c) chlorophyll a and b content of tomatoes harvested during S1 was 5.73 mg/100 g of fresh pericarp and then decreased continuously to 1.14 mg/100 g for S11; (d) the concentration (in mg/100 g of FW) of lycopene in the S8 red extract of 0.32 increased to 1.27 in S11; and (e) tomatoes harvested during S1 contained 48.2 mg of dehydrotomatine/100 g of FW, and this value continually decreased to 1.5 in S7, with no detectable levels in S8-S11. The corresponding alpha-tomatine content decreased from S1 (361) to S8 (13.8). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell assay IC(50) values showed that Hel299 lung cells, A549 lung cancer cells, and HeLa cervical carcinoma cells were highly susceptible to inactivation by glycoalkaloid-rich green tomato extracts. Chang normal liver cells and U937 lymphoma cells were less susceptible. The possible significance of the results for plant physiology and the diet is discussed. Topics: Alkaloids; Amino Acids; Antineoplastic Agents, Phytogenic; Carotenoids; Cell Proliferation; Chlorophyll; Female; Humans; Hydroxybenzoates; Lung Neoplasms; Plant Extracts; Solanum lycopersicum; Uterine Cervical Neoplasms | 2010 |
Evaluation of in vivo biological activities of tetrapyrrole ethanolamides as novel anticancer agents.
The tetrapyrrole ethanolamide derivatives, hematoporphyrin propylether ethanolamide (HPPEEA, 1) and pheophorbide a ethanolamide (PEA, 2) have previously shown some photodynamic activities in an in vitro photodynamic assay (D. Girard et al. Bioorg. Med. Chem. Lett. 18 (2008) 360-365). Extending this study to an in vivo one, HPPEEA and PEA were evaluated for their anticancer, toxicity, and pharmacokinetic activities in mouse animal models. The compounds showed moderate anticancer activity without apparent acute toxicity and without secondary tumour development. This indicates noteworthy anti-metastasis activity. The pharmacokinetic study revealed the compound fast clearances from body tissues. This is an important therapeutic concern since these compounds are light sensitive. Thus, the combination of photodynamic and anti-metastasis activities with fast tissue clearance indicates that HPPEEA and PEA are good candidates for further photodynamic treatment evaluations. Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Chlorophyll; Disease Models, Animal; Hematoporphyrins; Leukemia; Lung Neoplasms; Mice; Mice, Inbred C57BL | 2010 |
Identifying efficacious approaches to chemoprevention with chlorophyllin, purified chlorophylls and freeze-dried spinach in a mouse model of transplacental carcinogenesis.
The carcinogenic potential of dibenzo[a,l]pyrene (DBP) has been well characterized in numerous animal models. We have previously documented that a single dose of 15 mg/Kg DBP to pregnant mice late in gestation (GD 17) produces an aggressive T-cell lymphoma as well as lung and liver cancer in offspring. The current study examines the chemopreventative properties of chlorophyllin (CHL) and chlorophyll (Chl) in this transplacental carcinogenesis model. Pregnant B6129SF1 females, bred to 129S1/SvIm males, received purified diets incorporated with either 2000 p.p.m. CHL, 2000 p.p.m. Chl or 10% freeze-dried spinach beginning at gestation day 9. Lymphoma-dependent mortality was not significantly altered by maternal consumption of any of the diet and little effect on lung tumor burden in mice surviving to 10 months of age was observed. However, coadministration of CHL at 380 mg/Kg with DBP by gavage (molar ratio of 10:1, CHL:DBP) provided significant protection against DBP-initiated carcinogenesis. Offspring born to dams receiving CHL co-gavaged with DBP exhibited markedly less lymphoma-dependent mortality (P < 0.001). The degree of protection by CHL, compared with controls dosed with DBP in tricaprylin (TCP) as the vehicle, was less marked, but still significant. Coadministration of CHL (TCP as vehicle) also reduced lung tumor multiplicity in mice by approximately 50% and this was observed throughout the study (P < 0.005). This is the first demonstration that CHL can provide potent chemoprotection in a transplacental carcinogenesis model and support a mechanism involving complex-mediated reduction of carcinogen uptake. Topics: Animals; Anticarcinogenic Agents; Benzopyrenes; Carcinogens; Chlorophyll; Chlorophyllides; Diet; Female; Freeze Drying; Liver Neoplasms, Experimental; Lung Neoplasms; Lymphoma, T-Cell; Male; Maternal Exposure; Maternal-Fetal Exchange; Mice; Plant Preparations; Pregnancy; Spinacia oleracea | 2009 |
ABCG2-mediated transport of photosensitizers: potential impact on photodynamic therapy.
In photodynamic therapy (PDT), a tumor-selective photosensitizer is administered followed by activation of the photosensitizer by exposure to a light source of a given wavelength. This, in turn, generates reactive oxygen species that induce cellular apoptosis and necrosis in tumor tissue. Based on our earlier finding that the photosensitizer pheophorbide a is an ABCG2 substrate, we explored the ability of ABCG2 to transport photosensitizers with a structure similar to that of pheophorbide a. ABCG2-overexpressing NCI-H1650 MX50 bronchoalveolar carcinoma cells were found to have reduced intracellular accumulation of pyropheophorbide a methyl ester and chlorin e6 compared to parental cells as measured by flow cytometry. The ABCG2 inhibitor fumitremorgin C was found to abrogate ABCG2-mediated transport. Intracellular fluorescence of hematoporphyrin IX, meso-tetra(3-hydroxyphenyl)porphyrin, and meso-tetra(3-hydroxyphenyl)chlorin was not substantially affected by ABCG2. ABCG2-overexpressing cells also displayed decreased intracellular fluorescence of protoporphyrin IX generated by exogenous application of 5-aminolevulinic acid. Mutations at amino acid 482 in the ABCG2 protein known to affect substrate specificity were not found to impact transport of the photosensitizers. In cytotoxicity assays, ABCG2-transfected HEK-293 cells were 11-fold, 30-fold, 4-fold, and >7-fold resistant to PDT with pheophorbide a, pyropheophorbide a methyl ester, chlorin e6, and 5-aminolevulinic acid, respectively. ABCG2-transfected cells were not resistant to PDT with meso-tetra(3-hydroxyphenyl) chlorin. Neither multidrug resistance-associated protein 1 expression nor P-glycoprotein expression appreciably decreased the intracellular fluorescence of any of the photosensitizers examined as determined by flow cytometry. The results presented here implicate ABCG2 as a possible cause for cellular resistance to photodynamic therapy. Topics: Adenocarcinoma, Bronchiolo-Alveolar; Aminolevulinic Acid; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Biological Transport; Cell Proliferation; Chlorophyll; Chlorophyllides; Flow Cytometry; Fluorescence; Humans; Indoles; Kidney; Lung Neoplasms; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Photochemotherapy; Photosensitizing Agents; Porphyrins; Protoporphyrins; Tumor Cells, Cultured | 2005 |
Population pharmacokinetics of the photodynamic therapy agent 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a in cancer patients.
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 | 2003 |
Cytotoxic pheophorbide-related compounds from Clerodendrum calamitosum and C. cyrtophyllum.
Three pheophorbide-related compounds (1-3) were isolated from the leaves and stems of Clerodendrum calamitosum. The methyl ester of 3 (6) and the known (10S)-hydroxypheophytin a (7) also were isolated from leaves of the related plant Clerodendrum cyrtophyllum. Compounds 1 and 6 were isolated for the first time as naturally occurring products from a plant source. All structures were elucidated by detailed spectroscopic analysis. Biological evaluation showed that 1 and 2 exhibited strong cytotoxicity against human lung carcinoma (A549), ileocecal carcinoma (HCT-8), kidney carcinoma (CAKI-1), breast adenocarcinoma (MCF-7), malignant melanoma (SK-MEL-2), ovarian carcinoma (1A9), and epidermoid carcinoma of the nasopharynx (KB), and its etoposide- (KB-7d), vincristine- (KB-VCR), and camptothecin-resistant (KB-CPT) subclones. Compound 3 was less cytotoxic than 1 and 2. Compounds 4-6, the methyl esters of 1-3, showed strongly increased cytotoxicity compared with the parent acids. Interestingly, 6 was the most active derivative among these compounds. Compound 7 was inactive. Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Camptothecin; Cell Survival; Chlorophyll; Dose-Response Relationship, Drug; Drug Resistance; Etoposide; Female; Humans; Ileal Neoplasms; KB Cells; Kidney Neoplasms; Lung Neoplasms; Magnetic Resonance Spectroscopy; Melanoma; Molecular Structure; Ovarian Neoplasms; Plant Leaves; Plant Stems; Plants, Medicinal; Stereoisomerism; Structure-Activity Relationship; Taiwan; Tumor Cells, Cultured; Vincristine | 2001 |
Shielding effects and hypoxia in photodynamic therapy.
Photodynamic therapy (PDT) is a new modality to treat cancer. In clinical use, the procedure is limited by the poor penetration depth of the curative light, which ranges between 3 and 6 mm. The cause of this situation is not clear. Two hypotheses are discussed: shielding effect or hypoxia. To test both hypotheses, we designed an in vitro model. Suspensions and sediments of OAT-75 cells were incubated at 37 degrees C with pheophorbide a or 13(2)-hydroxy-bacteriopheophorbide a methyl ester, both second-generation sensitizers. Irradiation was done with laser light of suitable wavelength. In all experiments, cell death was seen on the surface of the sediment, i.e., near the border of the oxygen-containing atmosphere and opposite the site of the irradiation beam. Therefore, we should accept the hypoxia thesis. Topics: Absorption; Carcinoma, Small Cell; Cell Hypoxia; Chlorophyll; Humans; Laser Therapy; Lung Neoplasms; Photochemotherapy; Radiation-Sensitizing Agents; Tumor Cells, Cultured | 1994 |
ROENTGENOGRAPHIC AND DIRECT VISUALIZATION OF THORACIC DUCT.
Topics: Chlorophyll; Chylothorax; Chylous Ascites; Cineradiography; Geriatrics; Humans; Iodized Oil; Lung Neoplasms; Lymphography; Neoplasm Metastasis; Surgical Procedures, Operative; Thoracic Duct | 1964 |