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Vascular Shutdown as an Effect of Using Photodynamic Therapy to Treat Cancer

Vascular Shutdown as an Effect of Using Photodynamic Therapy to Treat Cancer PDF Author: Elizabeth Mary Pascucci
Publisher:
ISBN:
Category : Cancer
Languages : en
Pages : 152

Book Description
Photodynamic therapy (PDT) is a treatment that uses the combination of a photosensitizing drug and light to selectively kill cancer cells. PDT has many potential advantages such as minimal side effects, excellent cosmetic results, and no cellular resistance burdening traditional cancer treatments such as chemotherapy and radiation. Currently used in the clinic, a limitation is depth of light penetration; therefore, PDT can only be used to treat superficial disease. Our novel PDT agent utilizes two-photon laser technology, which increases the depth of light penetration, greatly increasing the potential uses. Our PDT is able to kill selective cells because the PDT drug has a targeting agent so the drug only goes to cancer cells that overexpress the Somatostatin receptor 2 (SSTr2) on their cell surface. Laser light irradiates the cancer cells causing cytotoxic singlet oxygen to be produced damaging the cells. It was observed, through in vivo imaging of the tumors before and after treatment, that vascular flow was diminished as a result of PDT. It is well established that angiogenesis must occur when a tumor reaches a certain size in order for the cells to remain viable and the tumor to continue to grow; therefore, vascular shutdown could be an important mechanism of how PDT works. A series of experiments on the tumor vasculature using in vivo imaging, immunohistochemistry and confocal microscopy has taken place since this observation to determine what may be happening. Results of these studies have shown that tumor vessels do express the SSTr2 and therefore effected by treatment. Experiments using a somatostatin analog, octreoate, detected by a fluor has shown that the endothelial cells do take the drug up. To ensure that it is blood vessels that were being studied, tumor tissue was stained for both SSTr2 and vonWillebrand Factor (vWF), a recognized endothelial cell marker. Staining patterns for both antibodies were similar. To strengthen the argument, SSTr2- negative tumor cells also showed a positive staining pattern of their vessels, demonstrating that even though the tumor cells are SSTr2- negative, the tumor vessels can be SSTr2-positive and thus responsive to PDT.

Vascular Shutdown as an Effect of Using Photodynamic Therapy to Treat Cancer

Vascular Shutdown as an Effect of Using Photodynamic Therapy to Treat Cancer PDF Author: Elizabeth Mary Pascucci
Publisher:
ISBN:
Category : Cancer
Languages : en
Pages : 152

Book Description
Photodynamic therapy (PDT) is a treatment that uses the combination of a photosensitizing drug and light to selectively kill cancer cells. PDT has many potential advantages such as minimal side effects, excellent cosmetic results, and no cellular resistance burdening traditional cancer treatments such as chemotherapy and radiation. Currently used in the clinic, a limitation is depth of light penetration; therefore, PDT can only be used to treat superficial disease. Our novel PDT agent utilizes two-photon laser technology, which increases the depth of light penetration, greatly increasing the potential uses. Our PDT is able to kill selective cells because the PDT drug has a targeting agent so the drug only goes to cancer cells that overexpress the Somatostatin receptor 2 (SSTr2) on their cell surface. Laser light irradiates the cancer cells causing cytotoxic singlet oxygen to be produced damaging the cells. It was observed, through in vivo imaging of the tumors before and after treatment, that vascular flow was diminished as a result of PDT. It is well established that angiogenesis must occur when a tumor reaches a certain size in order for the cells to remain viable and the tumor to continue to grow; therefore, vascular shutdown could be an important mechanism of how PDT works. A series of experiments on the tumor vasculature using in vivo imaging, immunohistochemistry and confocal microscopy has taken place since this observation to determine what may be happening. Results of these studies have shown that tumor vessels do express the SSTr2 and therefore effected by treatment. Experiments using a somatostatin analog, octreoate, detected by a fluor has shown that the endothelial cells do take the drug up. To ensure that it is blood vessels that were being studied, tumor tissue was stained for both SSTr2 and vonWillebrand Factor (vWF), a recognized endothelial cell marker. Staining patterns for both antibodies were similar. To strengthen the argument, SSTr2- negative tumor cells also showed a positive staining pattern of their vessels, demonstrating that even though the tumor cells are SSTr2- negative, the tumor vessels can be SSTr2-positive and thus responsive to PDT.

Advances in Photodynamic Therapy

Advances in Photodynamic Therapy PDF Author: Michael R. Hamblin
Publisher: Artech House
ISBN: 1596932783
Category : Medical
Languages : en
Pages : 601

Book Description
With today's focus on targeted and minimally invasive therapies, photodynamic therapy (PDT) is now being studied and used to combat many disease states and to investigate critical biological questions. This groundbreaking resource brings you the latest advances in photodynamic therapy and offers you a solid understanding of the design, delivery and dosimetry of the three basic ingredients of PDT - photosensitizers, light and oxygen. The book covers novel areas of mechanistic and innovative translational approaches. Moreover, it gives you an overview of the important medical applications of PDT, including approved treatments, clinical trials, and investigated therapies for cancer and non-malignant diseases.

Photodynamic Therapy

Photodynamic Therapy PDF Author: Barbara W. Henderson
Publisher: CRC Press
ISBN: 100010480X
Category : Photography
Languages : en
Pages : 480

Book Description
Covering all aspects of photodynamic therapy, 70 expert contributors from the fields of photochemistry, photobiology, photophysics, pharmacology, oncology and surgery, provide multidisciplinary discussions on photodynamic therapy - a rapidly-developing approach to the treatment of solid tumours.;Photodynamic Therapy: Basic Principles and Clinical Applications describes the molecular and cellular effects of photodynamic treatment; elucidates the complex events leading to photodynamics tissue destruction, particularly vascular and inflammatory responses; discusses the principles of light penetration through tissues and optical dosimetry; examines photosensitizer pharmacology and delivery systems; reviews in detail photosensitizer structure-activity relationships; illustrates novel devices that aid light dosimetry and fluorescence detection; and extensively delineates clinical applications, including early diagnosis and treatment.;A comprehensive and up-to-date reference, this book should be useful for oncologists, pharmacologists, surgeons, photobiologists, optical engineers, laser technicians, biologists, physicists, chemists and biochemists involved in cancer research, as well as graduate-level students in these disciplines.

Real-time Vascular Monitoring and Quantification of Photodynamic Therapy Via Interstitial Doppler Optical Coherence Tomography

Real-time Vascular Monitoring and Quantification of Photodynamic Therapy Via Interstitial Doppler Optical Coherence Tomography PDF Author: Beau A. Standish
Publisher:
ISBN: 9780494525845
Category :
Languages : en
Pages : 254

Book Description
Patients with prostate cancer are faced with several treatment options such as hormone therapy, external beam radiation and radical prostatectomy. However, long term disease-free survival remains elusive and is a critical issue for oncology clinicians. A safe and potentially curative salvage therapy is needed, and vascularly targeted photodynamic therapy (PDT) may prove to be the ideal treatment option for recurrent prostate cancer. Although tumor eradication may lead to cure, an important aspect of any treatment involves improving or retaining the patient's quality of life after therapy. If sensitive tissues within the prostate treatment region could be monitored and/or the biological treatment response predicted during PDT, the clinician could possibly minimize common treatment side effects such as incontinence, urethral stricture and impotence.The goal of this thesis was to extend current abilities of monitoring/predicting the PDT response, in an effort to reduce morbidity in prostate salvage therapy. An exciting and unique approach to monitor and quantify the PDT-induced vascular response is interstitial (IS) Doppler optical coherence tomography (DOCT), which can image tissue structure at near-cellular-levels, while also detecting the presence of microvasculature. However, these advantageous imaging characteristics are limited to a depth of 1-3mm. As the prostate is a deeply situated organ, a novel minimally invasive needle based IS-DOCT probe was developed to gain access to deep tissue such as the prostate. A xenograft Dunning rat prostate pilot study demonstrated the ability of IS-DOCT to detect and monitor PDT-induced vascular effects, while a follow-up study highlighted the sensitivity of the IS-DOCT system to detect changes in the vascular shutdown rate as a function of PDT surface irradiances. Finally, in a multi-modality study, including Monte Carlo modeling and high frequency ultrasound, a correlation between the vascular shutdown rate and biological endpoint of tumor necrosis was observed demonstrating that IS-DOCT may provide a predictive PDT imaging metric. In conclusion, this thesis presents a technique to monitor and quantify real-time PDT-induced vascular changes, suggesting an important role for IS-DOCT in pre-treatment planning, feedback control for treatment optimization, and post PDT treatment assessment.

Treatment of Mestastatic Breast Cancer by Photodynamic Therapy Induced Anti-Tumor Immunity in a Murine Model

Treatment of Mestastatic Breast Cancer by Photodynamic Therapy Induced Anti-Tumor Immunity in a Murine Model PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 13

Book Description
One in 8 women in the United States will develop breast cancer during her lifetime. Deaths are due to tumors that have metastasized. 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. PDT produces 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. 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 is a mechanism to deplete regulatory T cells; these cells play a role in the immunosuppression activity of tumors. In combination with PDT, cyclophosphamide increases the survival. The second alternative therapy is the use of a novel combination of the immunostimulant CpG Oligodeoxynucleotides (CpG-ODN) and PDT. CpG-ODN directly or indirectly triggers B cells, NK cells, 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. We propose that a rational choice of immune stimulant is an ideal addition to PDT regimens.

Photodynamic Therapy

Photodynamic Therapy PDF Author: Thierry Patrice
Publisher: Royal Society of Chemistry
ISBN: 1847551653
Category : Medical
Languages : en
Pages : 292

Book Description
For centuries, light has been used to cure various diseases. However, it is only recently that a new medical field has arisen. Photodynamic therapy (PDT), also known as photochemotherapy, is a fast growing technique which was initially devoted to cancer care but which is now recognised as a promising treatment technique in a variety of clinical fields. Written by recognised experts, Photodynamic Therapy provides a comprehensive explanation of what PDT is and how it has developed as a technique in areas such as the detection of lung cancer and applications in dermatology, gynaecology and neurosurgery. This book is ideal both as an introduction to PDT and as an informative text for those wishing to expand their knowledge. Practitioners in biological sciences, biotechnology and medicinal and pharmaceutical chemistry will find it an invaluable source of information.

NanoBioMedicine

NanoBioMedicine PDF Author: Shailendra K. Saxena
Publisher: Springer Nature
ISBN: 9813298987
Category : Medical
Languages : en
Pages : 510

Book Description
This book provides a comprehensive overview of the recent trends in various Nanotechnology-based therapeutics and challenges associated with its development. Nanobiotechnology is an interdisciplinary research that has wide applications in the various fields of biomedical research. The book discusses the various facets of the application of Nanotechnology in drug delivery, clinical diagnostics, Nanomedicine and treatment of infectious and chronic diseases. The book also highlights the recent advancements on important devices and applications that are based on Nanotechnology in medicine and brief the regulatory and ethical issues related to nanomedical devices. It also reviews the toxicological profile of various nanomaterials and emphasizes the need for safe nanomaterials for clinical use. Finally, the book discusses the recent developments of potential commercial applications of Nanotechnology.

Therapeutic Ultrasound

Therapeutic Ultrasound PDF Author: Jean-Michel Escoffre
Publisher: Springer
ISBN: 3319225367
Category : Medical
Languages : en
Pages : 459

Book Description
This book highlights advances and prospects of a highly versatile and dynamic research field: Therapeutic ultrasound. Leading experts in the field describe a wide range of topics related to the development of therapeutic ultrasound (i.e., high intensity focused ultrasound, microbubble-assisted ultrasound drug delivery, low intensity pulsed ultrasound, ultrasound-sensitive nanocarriers), ranging from the biophysical concepts (i.e., tissue ablation, drug and gene delivery, neuromodulation) to therapeutic applications (i.e., chemotherapy, sonodynamic therapy, sonothrombolysis, immunotherapy, lithotripsy, vaccination). This book is an indispensable source of information for students, researchers and clinicians dealing with non-invasive image-guided ultrasound-based therapeutic interventions in the fields of oncology, neurology, cardiology and nephrology.

Systemic Drug Delivery Strategies

Systemic Drug Delivery Strategies PDF Author: Mansoor M. Amiji
Publisher: Academic Press
ISBN: 0323909256
Category : Medical
Languages : en
Pages : 590

Book Description
Systemic Drug Delivery Strategies: Delivery Strategies and Engineering Technologies in Cancer Immunotherapy, Volume 2 examines the challenges of delivering immuno-oncology therapies, focusing specifically on the multiple technologies of affective drug delivery strategies. Immuno-oncology (IO) is a growing field of medicine at the interface of immunology and cancer biology leading to development of novel therapeutic approaches, such as chimeric antigen receptor T-cell (CAR-T) and immune checkpoint blockade antibodies, that are clinically approved approaches for cancer therapy. Although currently approved IO approaches have shown tremendous promise for select types of cancers, broad application of IO strategies could even further improve the clinical success, especially for diseases such as pancreatic cancer, brain tumors where the success of IO so far has been limited. This volume of Delivery Strategies and Engineering Technologies in Cancer Immunotherapy discusses methods of targeting tumors, CRISPR technology, and vaccine delivery among many other delivery strategies. Systemic Drug Delivery Strategies: Delivery Strategies and Engineering Technologies in Cancer Immunotherapy, Volume 2 creates a comprehensive treaty that engages the scientific and medical community who are involved in the challenges of immunology, cancer biology, and therapeutics with possible solutions from the nanotechnology and drug delivery side. - Comprehensive treaty covering all aspects of immuno-oncology (IO) - Novel strategies for delivery of IO therapeutics and vaccines - Forecasting on the future of nanotechnology and drug delivery for IO

Nano-Oncologicals

Nano-Oncologicals PDF Author: Maria José Alonso
Publisher: Springer
ISBN: 3319080849
Category : Medical
Languages : en
Pages : 478

Book Description
This authoritative volume focuses on emerging technologies in cancer nano medicine, characterized by their multi-functionality and potential to address simultaneously diverse issues of clinical relevance in the treatment of cancer. The book consists of sixteen chapters divided into six sections: 1) Biological Barriers in Cancer; 2) Tumor Targeting; 3) Targeting the Immune System; 4) Gene Therapy; 5) Nano theranostics and 6) Translational Aspects of Nano-Oncologicals. The volume starts with an introduction describing the biological barriers associated with cancer therapy and highlighting ways to overcome such barriers through the use of nanotechnology. This is followed by an analysis of the two major targeting strategies currently under investigation in cancer therapy: namely, the targeting of cancer cells and the targeting of the immune system. In the first case, the book presents liposomal and polymer-based therapies, including photodynamic approaches. In the second case, it analyzes in detail the possibility of either improving the efficiency of the immune system toward preventing cancer progression (cancer immunomodulation) or generating responses against specific cancer antigens (cancer vaccines). Beyond these targeting options, Nano-Oncologicals: New Targeting and Delivery Approaches presents the most recent technological advances in the area of nucleic acid-based therapies, along with those in the area of theranostics, where the design of multifunctional nano carriers becomes vital. Following the study of the most promising nanotechnologies around the development of nano-oncologicals, the book ends with an overview of regulatory and toxicological issues, which are critical in their translational pathway, and the presentation of a nucleic acid-based therapy case-study. This book is an important resource for scientists interested in the design and development of anticancer nanotechnologies and also to those aiming to push their technology through clinical development.