Dr. Ana P. Castano Profile

Dr. Ana P. Castano

at Massachusetts General Hospital

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Author

Publications (11)

Proceedings Article | 13 July 2009 Paper

Anti-tumor immune response after photodynamic therapy

Pawel Mroz, Ana Castano, Mei Wu, Andrew Kung, Michael Hamblin

Proceedings Volume 7380, 73800F (2009) https://doi.org/10.1117/12.822994

KEYWORDS: Tumors, Photodynamic therapy, Lymphatic system, Proteins, Cancer, Colon, Tumor growth modeling, Molecules, Oncology, In vitro testing

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Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naïve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp3+) and potentiate immune response after PDT in the case of tumors that express self-antigens. These data suggest that PDT alone will stimulate a strong immune response when tumors express a robust antigen, and in cases where tumors express a self-antigen, T-reg depletion can unmask the immune response after PDT.

Proceedings Article | 25 February 2009 Paper

Stimulation of dendritic cells enhances immune response after photodynamic therapy

Pawel Mroz, Ana Castano, Michael Hamblin

Proceedings Volume 7178, 717803 (2009) https://doi.org/10.1117/12.809630

KEYWORDS: Tumors, Photodynamic therapy, Cancer, Receptors, Bone, Lymphatic system, Tumor growth modeling, Molecules, Breast cancer, In vitro testing

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Proceedings Article | 21 February 2007 Paper

Low-level light therapy for Zymosan induced arthritis in rats

Ana Castano, Tianhong Dai, Tatiana Demidova-Rice, Elena Salomatina, Anna Yaroslavsky, Ilya Yaroslavsky, Richard Cohen, William Apruzzese, Michael Smotrich, Michael Hamblin

Proceedings Volume 6428, 64280F (2007) https://doi.org/10.1117/12.698193

KEYWORDS: Wound healing, Laser therapeutics, Low level phototherapy, Inflammation, Animal model studies, Phototherapy, Chromophores, Acquisition tracking and pointing, Near infrared, Medicine

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Proceedings Article | 13 February 2007 Paper

Photodynamic therapy stimulates anti-tumor immunity in a murine model

Pawel Mroz, Ana Castano, Mei Wu, Andrew Kung, Michael Hamblin

Proceedings Volume 6438, 643803 (2007) https://doi.org/10.1117/12.697630

KEYWORDS: Tumors, Photodynamic therapy, Cancer, Tumor growth modeling, Proteins, Oxygen, Colon, Computer programming, In vivo imaging, Potassium

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Cancer is a leading cause of death among modern peoples largely due to metastatic disease. The ideal cancer treatment should target both the primary tumor and the metastases with the minimal toxicity. This is best accomplished by educating the body's immune system to recognize the tumor as foreign so that after the primary tumor is destroyed, distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. We here report on PDT of mice bearing tumors that either do or do not express an established TAA. We utilized a BALB/c colon adenocarcinoma cell line termed CT26.CL25 retrovirally transduced to stably express &bgr;-galactosidase ( &bgr;-gal, a bacterial protein), and its non-&bgr;-gal expressing wild-type counterpart termed CT26 WT, as well as the control cell line consisting of CT26 transduced with the empty retroviral vector termed CT26-neo. All cells expressed class I MHC restriction element H-2Ld syngenic to BALB/c mice. Vascular PDT with a regimen of 1mg/kg BPD injected IV, and 120 J/cm² of 690-nm laser light after 15 minutes successfully cured 100% of CT26.CL25 tumors but 0% of CT26-neo tumors and 0% of CT26 WT tumors. After 90 days tumor free interval the CT26.CL25 cured mice were rechallenged with CT26.CL25 tumor cells and 96% rejected the rechallenge while the CT26.CL25 cured mice did not reject a CT26 WT tumor cell challenge. Experiments with mice bearing two CT26.CL25 tumors (one in each leg) and only one tumor treated with PDT, showed that the immune response was strong enough to destroy an already established tumor in 70 of the mice and this effect was not seen with mice bearing two CT26 WT tumors. We expect these studies will lead to an understanding of the relevant determinants of immune response after PDT that could be rapidly applied to patient-selection and improvement in outcome for PDT for cancer.

SPIE Journal Paper | 1 March 2006 Open Access

Photosensitizer delivery to vulnerable atherosclerotic plaque: comparison of macrophage-targeted conjugate versus free chlorine(e6)

Ahmed Tawakol, Ana Castano, Florencia Anatelli, Gregory Bashian, Jeremy Stern, Touqir Zahra, Faten Gad, Stephanie Chirico, Atosa Ahmadi, Alan Fischman, James Muller, Michael Hamblin

JBO, Vol. 11, Issue 02, 021008, (March 2006) https://doi.org/10.1117/12.10.1117/1.2186039

KEYWORDS: Arteries, Luminescence, Tissues, Natural surfaces, Picosecond phenomena, Tissue optics, Molecules, Injuries, Medicine, Liver

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Proceedings Article | 24 February 2006 Paper

Combination immunotherapy and photodynamic therapy for cancer

Michael Hamblin, Ana Castano, Pawel Mroz

Proceedings Volume 6087, 608702 (2006) https://doi.org/10.1117/12.646275

KEYWORDS: Tumors, Photodynamic therapy, Cancer, Receptors, Therapeutics, Lymphatic system, Cell death, Oxygen, Proteins, Resistance

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Proceedings Article | 23 February 2006 Paper

Enhancing photodynamic therapy of a metastatic mouse breast cancer by immune stimulation

Ana Castano, Michael Hamblin

Proceedings Volume 6087, 608703 (2006) https://doi.org/10.1117/12.646242

KEYWORDS: Tumors, Photodynamic therapy, Breast cancer, Tumor growth modeling, Oxygen, Therapeutics, Picosecond phenomena, Cancer, Cell death, Receptors

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One in 8 women in the United States will develop breast cancer during her lifetime and 40,000 die each year. Deaths are due to tumors that have metastasized despite local control. Photodynamic therapy (PDT) is a promising cancer treatment in which a photosensitizer (PS) accumulates in tumors and is subsequently activated by visible light of an appropriate wavelength. The energy of the light is transferred to molecular oxygen to produce reactive oxygen species that produce cell death and tumor ablation. Mechanisms include cytotoxicity to tumor cells, shutting down of the tumor vasculature, and the induction of a host immune response. The precise mechanisms involved in the PDT-mediated induction of anti-tumor immunity are not yet understood. Potential contributing factors are alterations in the tumor microenvironment via stimulation of proinflammatory cytokines and direct effects of PDT on the tumor that increase immunogenicity. We have studied PDT of 410.4 variant 4T1 tumors growing in the mammary fat pad (orthotopic) in Balb/c mice and which produce metastasis. We have shown that a PDT regimen that produces vascular shutdown and tumor necrosis leads to initial tumor ablation but the tumors recur at the periphery. We studied the combination of PDT with immunostimulating therapies. Low dose cyclophosphamide (CY) is a specific mechanism to deplete the regulatory T cells (CD4+CD25+), these cells play an important role in the immunosuppression activity of tumors. In combination with PDT that produces release of tumor specific antigens, this immunostimulation may lead to generation of cytotoxic CD8 T-lymphocytes that recognize and destroy the tumor. The second alternative therapy is the use of a novel combination of the immunostimulant CpG oligodeoxynucleotides (CpG-ODN) and PDT. CpG-ODN is recognized by Toll-like receptor 9 and directly or indirectly triggers B cells, NK cells, monocyte-macrophages and dendritic cells to proliferate, mature and secrete cytokines, chemokines and immunoglobulins. Both these novel combinations gave significantly enhanced therapeutic benefit not seen with single treatments alone. Tumors grew more slowly and mice lived significantly longer, although cures were rare. We propose that a rational choice of immune stimulant is an ideal addition to PDT regimens.

Proceedings Article | 22 February 2006 Paper

Dye-Enhanced Reflectance and Fluorescence Confocal Microscopy as an Optical Pathology Tool

Anna Yaroslavsky, Elena Salomatina, John Novak, Ivan Amat-Roldan, Ana Castano, Michael Hamblin

Proceedings Volume 6091, 609107 (2006) https://doi.org/10.1117/12.658303

KEYWORDS: Confocal microscopy, Luminescence, In vivo imaging, Reflectivity, Skin cancer, Cancer, Tissues, Skin, Tissue optics, Tumors

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Proceedings Article | 15 April 2005 Paper

Anti-tumor immunity generated by photodynamic therapy in a metastatic murine tumor model

Ana Castano, Michael Hamblin

Proceedings Volume 5695, (2005) https://doi.org/10.1117/12.589340

KEYWORDS: Tumors, Photodynamic therapy, Cancer, Oncology, Oxygen, Cell death, Tissue optics, Light emitting diodes, Picosecond phenomena, Molecules

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Proceedings Article | 1 July 2004 Paper

Photodynamic therapy cures green fluorescent protein expressing RIF1 tumors in mice

Ana Castano, Qingde Liu, Michael Hamblin

Proceedings Volume 5319, (2004) https://doi.org/10.1117/12.528381

KEYWORDS: Tumors, Photodynamic therapy, Green fluorescent protein, Cancer, Luminescence, Picosecond phenomena, Proteins, Tissues, Oncology, Oxygen

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Proceedings Article | 12 September 2003 Paper

Macrophage-targeted photodynamic detection of vulnerable atherosclerotic plaque

Michael Hamblin, Ahmed Tawakol, Ana Castano, Faten Gad, Touqir Zahra, Atosa Ahmadi, Jeremy Stern, Bernhard Ortel, Stephanie Chirico, Azadeh Shirazi, Sakeena Syed, James Muller

Proceedings Volume 4949, (2003) https://doi.org/10.1117/12.476218

KEYWORDS: Luminescence, Tissues, Arteries, Confocal microscopy, Picosecond phenomena, Virtual point source, Receptors, Photodynamic therapy, Blood, Tissue optics

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Rupture of a vulnerable atherosclerotic plaque (VP) leading to coronary thrombosis is the chief cause of sudden cardiac death. VPs are angiographically insignificant lesions, which are excessively inflamed and characterized by dense macrophage infiltration, large necrotic lipid cores, thin fibrous caps, and paucity of smooth muscle cells. We have recently shown that chlorin(e6) conjugated with maleylated albumin can target macrophages with high selectivity via the scavenger receptor. We report the potential of this macrophage-targeted fluorescent probe to localize in VPs in a rabbit model of atherosclerosis, and allow detection and/or diagnosis by fluorescence spectroscopy or imaging. Atherosclerotic lesions were induced in New Zealand White rabbit aortas by balloon injury followed by administration of a high-fat diet. 24-hours after IV injection of the conjugate into atherosclerotic or normal rabbits, the animals were sacrificed, and aortas were removed, dissected and examined for fluorescence localization in plaques by fiber-based spectrofluorimetry and confocal microscopy. Dye uptake within the aortas was also quantified by fluorescence extraction of samples from aorta segments. Biodistribution of the dye was studied in many organs of the rabbits. Surface spectrofluorimetry after conjugate injection was able to distinguish between plaque and adjacent aorta, between atherosclerotic and normal aorta, and balloon-injured and normal iliac arteries with high significance. Discrete areas of high fluorescence (up to 20 times control were detected in the balloon-injured segments, presumably corresponding to macrophage-rich plaques. Confocal microscopy showed red ce6 fluorescence localized in plaques that showed abundant foam cells and macrophages by histology. Extraction data on aortic tissue corroborated the selectivity of the conjugate for plaques. These data support the strategy of employing macrophage-targeted fluorescent dyes to detect VP by intravascular spectrofluorimetry. It may also be possible to use macrophage-targeted PDT to therapeutically modify inflammatory cell-laden VPs leading to plaque stabilization and reduction of sudden cardiovascular death.

Showing 5 of 11 publications

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