Breast Cancer Survivors

Chemo Secrets From a Breast Cancer Survivor

Undergoing chemotherapy can be one of the most terrifying things that you go through in your life. One of the most frightening things about chemotherapy is the lack of real information that most people have about it, and the unknown makes it so much more frightening as a result. This eBook, written by a young cancer survivor gives you the real story about what chemo is all about. The most valuable information you can get about chemotherapy is from someone that has already experienced it. This PDF eBook allows you to download and read it as soon as your order it. You can begin your journey of reassurance as soon as you want! Because that's what this is about: chemo does not have to be a terrifying unknown! Other people have gone through it before, and want to help you through it as well! This eBook is the guide through chemo that many people wish they could have had, and now you can have it yourself! More here...

Chemo Secrets From a Breast Cancer Survivor Summary

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Author: Nalie Augustin
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Breast Cancer and Nanoparticles

Breast cancer is the most common malignancy in women in the United States, with approximately 180,000 new cases diagnosed in this country annually. Breast cancer is the third most common cause of cancer death (after lung cancer and colon cancer) in the United States. Statistics show that a woman has a one in eight chance of developing breast cancer during her life. In 2007, breast cancer is expected to cause Some of the treatment of breast cancer includes surgery, hormone therapy, chemotherapy, and radiation therapy. Now scientists are experimenting with nanoparticles to treat breast cancer. Faster Results for Breast Cancer. Pathologists Use Digital Imaging to Speed up Cancer Diagnosis. Science Daily. Go to http www. sciencedaily.com videos 2006-02-06 Please note the use of magnetic particles as a heat treatment to kill breast cancer cells in humans is still conducted only in laboratories at the preclinical and developmental stage. Preclinical tests for humans are still in the future,...

How did you get involved in breast cancer research

One of your research projects is to continue to collect and evaluate data to demonstrate that adding an anti-HER2 agent (Herceptin) to chemotherapy patients with HER2 positive breast cancer can help prevent recurrence of breast cancer in patients. HER2 is a protein found on the membrane (with a portion in the surface) of cells that helps regulate cell growth. However, when the amount and type of HER2 protein are altered, this leads to increased cell growth and possibility of cancer spread, as a result of increased breast cancer aggressiveness. Herceptin is a monoclonal antibody that targets the extracellular domain of the HER2 protein. This treatment is used for metastatic breast cancer, but also to diminish the risk of tumor reappearance (and improve survival) after breast cancer surgery. Metastatic, describes a cancer that has spread to distant organs from the original tumor site. Metastatic breast cancer is the most advanced stage of breast cancer. Herceptin slows the growth and...

Drug Delivery to Breast Cancer

Resistance to cancer chemotherapy involves both altered drug activity at the designated target and modified intra-tumor pharmacokinetics (e.g., uptake and metabolism). Two proteins in particular P-glycoprotein (P-gp) and MDR-associated protein (MRP2) are responsible for MDR associated with a variety of cancers.169 BCRP (breast cancer resistant protein) is another type of protein that appears to play a major role in the MDR phenotype of a specific human breast cancer.170 Cancer cells overexpressing these proteins are resistant to several chemotherapeutic agents, including the anthracyclines, and show a reduced nuclear accumulation of anthracyclines.171 The ability of

Cancer Chemotherapy

Selective intracellular drug delivery assumes great importance in cancer chemotherapy, because most of the anti-cancer drugs are cytotoxic to normal cells. To achieve selective drug targeting, drug delivery scientists have been exploiting the differences in cell physiology of normal and cancerous cells 30 . Various approaches based on these differences include (i) the use of high-molecular-weight polymer-drug conjugates that preferentially accumulate in solid tumor tissue by enhanced permeability and retention (EPR) effect

Richard E Smalley 19432005

I sit before you today with very little hair on my head. It fell out a few weeks ago as a result of the chemotherapy I've been undergoing to treat a type of non-Hodgkin's lymphoma. While I am very optimistic, this chemotherapy is a very blunt tool. It consists of small molecules, which are toxic they kill cells in my body. Although they are meant to kill only the cancer cells, they kill hair cells too, and cause all sorts of other havoc. Now, I'm not complaining. Twenty years ago, without even this crude chemotherapy, I would already be dead. But 20 years from now, I am confident we will no longer have to use this blunt tool. By then, nanotechnology will have given us specially engineered drugs, which are nanoscale cancer-seeking missiles, a molecular technology that specifically targets just the mutant cancer cells in the human body and leaves everything else blissfully alone. . I may not live to see it. But, with your help, I am confident it will happen. Cancer at least the type...

Nanocarriers For Gene Delivery

Without any changes in the functions of other genes using synthetic oligonucleotides such as antisense DNA, decoy oligonucleotide, and siRNA have been also considered as a novel anti-tumor chemotherapy. However, because pDNA and synthetic oligonucleotides are easily degraded or metabolized, there is no cell selectivity, and enough transgene expression or inhibition of target gene expression for effective therapy could not be achieved by the administration of naked pDNA or oligonucleotides. Therefore, for effective therapy, it is essential to develop a novel carrier that makes it possible to deliver such drugs to the target tissue or cells.

Optical Properties of Gold Nanoshells

As previously stated, the optical response of nanoshells depends drastically on the relative size of the dielectric core and thickness of the gold layer. The ability to fine-tune nanoshells to have optical resonance varied over a broad region ranging from the near-UV to the mid-infrared is very important for tissue imaging. It has been demonstrated that nanoshells can be developed to highly scatter light within this spectral region as would be desired for many imaging applications alternatively, nanoshells may be engineered to function as highly effective NIR absorbers permitting photothermal-based therapy applications as well (Loo et al. 2004) dual scattering absorbing nanoshells can also be fabricated (Loo et al. 2005). For instance, the conventional NIR dye indocyanine green has an absorption cross-section of 10-20 m2 at 800 nm, while the cross-section of absorbing nanoshells can be as high as 4 x 10-14 m2, approximately a million-fold increase in the absorption cross-section...

Nanoshells in Cancer Diagnostics and Treatment

Researchers have developed a novel approach to combine cancer diagnostics and therapeutics based on the use of gold nanoshells as near-infrared (NIR) absorbers. In one exciting in vitro study (Loo et al. 2004), 120 nm diameter silica core-10 nm gold shell nanoparticles were fabricated to provide peak optical scattering and absorption efficiencies in the NIR region ( 800 nm). These nanoshells were used for combined imaging and therapy of SKBr3 breast cancer cells. To target these cancer cells, anti-HER2 was conjugated onto the nanoshells to specifically deliver the conjugated anti-HER2-nanoshells to SKBr3 breast adenocarcinoma cells which overexpressed HER2. For cells incubated with conjugated anti-HER2 nanoshells, significantly increased scatter-based optical contrast due to nanoshell binding was achieved as compared to the control cell groups. The second function of these conjugated nanoshells, i.e., therapy, was achieved via photothermal therapy. Incubated cells were exposed to NIR...

Modular Functionalities At The Biosynthetic Interface 521 Targeting

For example, the 34 amino acid, cationic peptide F3, which has been used to deliver quantum dots to tumor endothelium, was uncovered initially by a blind-page display screen in a breast cancer xenograft model and later found to bind cell surface nucleolin expressed on tumor endothelium and cancer cells.6,33,34

Superparamagnetic Nanoparticles SPMNPs

They have some attractive properties that make them suitable for tumor imaging and tumor treatment. First, they have a controllable nano size. Second, they possess magnetic properties that render them unique in magnetic-based imaging techniques and magnetic-based treatment methods. For example, SPMNPs can be conjugated with drugs, targeted to tumors using magnets, then they can absorb energy from a time-varying magnetic field to be heated resulting in the release of drugs while heat elevation can cause chemotherapy and radiation therapy to be more effective or can directly destroy tumor tissues. In this section, we review the use of SPMNPs in magnetic resonance imaging (MRI), hyperthermia treatment, and magnetic-based drug delivery.

Magnetic Targeting of Spmnp Drug Conjugates

A clear advantage of using SPMNPs is that they can be directed to tumor sites using an external magnetic field. Using this method, SPMNPs conjugated with anticancer drugs can be delivered to tumors locally to release therapeutic agents and the conjugate can also be held by the magnetic field in a place at the desired site leading to increased drug delivery efficacy. For example, investigators have used 100 nm (hydrodynamic diameter) iron oxide superparamagnetic particles bound to mitox-antrone (that is an agent used in the treatment of certain types of cancer including metastatic breast cancer and acute myeloid leukemia) to target squamous cell carcinoma in rabbits (Alexiou et al. 2000). A magnetic flux density of a maximum of 1.7 T was used to produce an inhomogeneous magnetic field that was focused on the tumor in order to attract SPMNPs. A very high concentration of SPMNPs within the tumor after intra-arterial infusion was achieved. Importantly, this application method resulted in...

Energy Transfer To The Tumor

Cancer therapies include a broad array of options including surgery, chemotherapy, and radiotherapy. Another set of mechanisms include those by which energy is transferred from an external source into tissue, many of which are mediated by nanoparticles. Techniques such as nanoparticle-mediated laser energy absorption 48,49 , microwave absorption 50,51 , enhanced radiation absorption 52 , and magnetic-field energy absorption 53 are a few examples of studies demonstrating nanoparticle-mediated energy transfer. Magnetic field energy absorption approaches use a wide variety of mediator materials from macroscopic needles to nanoparticles 54-56 . This review will focus on energy transfer mediated by magnetic nanoparticles. Coupling energy in the form of a time-varying magnetic field into tumors mediated by magnetic nanoparticles has been an active area of research for more than a decade. These mechanisms are included in the methodology broadly referred to as hyperthermia, which is used as...

Drug Release Characteristics and Drug Biodistribution Profiles

Since polymeric nanoparticles can be fabricated from various polymers by many different methods, the release characteristics of the nanoparticles loaded with drugs can be fine-tuned. By varying the polymer composition of the particle and its morphology, it is possible to fine-tune a variety of controlled-release characteristics, allowing moderate continuous doses over prolonged periods of time (Anderson and Shive 1997). The degradation rate of the polymers and the corresponding drug release rate can vary from days to months and can be easily manipulated by varying the composition of polymers or copolymers (Brigger et al. 2002). For example, polymeric nanoparticles were formulated from PLGA-monomethoxypoly (ethylene-glycol) (mPEG) copolymers of different compositions (PLGA-mPEG molar ratios) and loaded with cisplatin (that is, a platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas, some carcinomas, and lymphomas) (Avgoustakis et al. 2002). The...

Hype or a reaction to complexity

Clearly, nanotechnology is grounded in scientific reality. Its products range from the banal to the astonishing - from paint (which has long-contained nanoparticles, certainly long before we coined the term) to nanotechnology treatments for breast cancer (curing cancer is an NNI 'challenge goal') (Hiemstra, 2003). These products, some in a hypothetical future, penetrate

Conventional Neurosurgical Treatments

Chemotherapeutic agents, radiation treatment, and surgical excision are conventional methods to diminish or remove the tumors to regain normal neurological function 16 . Unfortunately, invasiveness or encroachment of the tumor upon healthy brain tissue is the deterrent to cure for most brain tumors. This behavior is especially true of gliomas, which are the most common form of primary tumors and exhibit a propensity to infiltrate healthy tissue rapidly while increasing malignant potential 36 . Surgery is the chief form of treatment for brain tumors such as meningiomas, which lie within the membranes covering the brain, or in parts of the brain that can be removed without damaging critical neurological functions. Because a tumor will recur if any tumor cells are left behind, the neurosurgeon's goal is to remove the entire tumor whenever possible. Radiation therapy and chemotherapy, in FIGURE 6.7. Photograph of GLIADEL wafers for the chemotherapy of malignant brain tumors. These...

The Federal Role in Nanoscale Research and Development Basic and Applied

The appropriate federal role in supporting applied research has been debated publicly in recent years. The mission agenciessuch as the Department of Defense (DoD), the National Aeronautics and Space Administration (NASA), and the National Institutes of Health (NIH)have an agreed role in supporting applied research and even product development that will directly contribute to their respective missions. These agencies have identified numerous opportunities where applied research in nanotechnology can make important contributions to their missions. Examples include DoD support for development of nanotechnology-enabled sensors to detect chemical, biological, radiological, and explosives agents NASA support for development of flexible, lightweight, and superstrong materials for future spacecraft and NIH support for development of nanostructures that can be used to selectively target tumor cells with either radiation or chemotherapy.

Special Features Of Vessels In Disease

Detailed analysis of the specificity of the tumor-homing peptides we have selected from phage libraries shows that some of the peptides recognize vascular markers that are common to all tumors, but some only bind to the vessels in a limited range of tumors. The former recognize angiogenesis-related proteins. The molecules recognized by the peptides reactive with a restricted range of tumors are not known, but it is likely that the tumor tissue sends the endothelium the signals necessary for the expression of specific molecules. We are currently attempting to identify tumor-homing peptides that would be specific for the blood vessels or lymphatics of a given tumor type, such as prostate cancer or breast cancer.

Research Focus Areas of Other NNI Agencies

The National Institutes of Health has many Institutes that are funding research into nanotechnology-based disease detection, prevention, and therapeutics, as well as tools that will allow greater understanding of the biological processes that influence our health. Nanotechnology research can develop unique capabilities to measure and manipulate on the size scale of individual cells. Efforts have already been funded to develop new tools that gather information on macromolecular systems in living cells or organisms. Other funding is targeted to detection and treatment of specific diseasesfor example, research into targeted imaging contrast agents for detecting very small numbers of cancer cells at the earliest stages of the disease, and even nanoparticles that can selectively deliver chemotherapy drugs only to tumors without damaging normal tissues. The National Institutes of Health, like most federal agencies, funds considerable other basic nanoscale research that it does not formally...

Nano Interview Dr Edith Perez

To learn more about breast cancer, the author was able to contact Edith A., Perez, who is a Medical Doctor and a Professor of Medicine at the Mayo Medical School in Jacksonville, Florida. She is also the Director of Clinical Investigations and the Director of the Breast Cancer Program. Dr. Perez took time out to discuss her professional background and her medical work in breast cancer. A small percentage of men can also get breast cancer. Dr. Edith A., Perez is a Medical Doctor and a Professor of Medicine at the Mayo Medical School in Jacksonville, Florida. She is also the Director of Clinical Investigations and the Director of the Breast Cancer Program. (Courtesy Dr. Edith Perez)

Approaches For Cancer Targeting To Specific Cancer Types

Are lectin-carbohydrate, ligand-receptor and antibody-antigen. One limitation of using these targeting strategies is that the lectin-carbohydrate targeting systems are usually targeted to whole organs, making them inappropriate for targeting a cancerous part of a particular organ or tissue. New antibody systems show a great deal of promise. Unfortunately, they also have potentially harmful side effects such as advanced gastric adenocarcinoma. The latter arises when one attempts to target breast cancer on account of the fact that antigen-positive normal cells to the antibody BR96 in gastric mucosa, small intestine, and pancreas. Some of the aspects of angiogenic targeting mentioned here have already been covered elsewhere in this chapter. Specific targeting systems that are in use as cancer therapeutics are shown in Table 12.1.8,72

Polyethylene Glycol Modified Thiolated Gelatin Nanoparticles

These nanoparticles, prepared by the desolvation method, were post-PEGylated with polyethylene glycol-succinimidyl glutarate (PEG-SG) of molecular weight 2,000 Da. The radiolabeled (111Indium) long-circulating (PEG-modified) thiolated-gelatin nanoparticles were injected intravenously into mice bearing human breast cancer (MDA-MB435) xenografts. The biodistribution and pharmacokinetics of these particles were compared to those of nanoparticles prepared from thio-lated-gelatin, gelatin, and PEG-modified gelatin. The unmodified gelatin and thiolated gelatin nanoparticles were shown to have a plasma half-life of approximately three hours. Upon modification with PEG, the nanoparticles were found to have prolonged circulation times extending up to

In Vitro Cytotoxicity

Shuai et al. reported delayed cell death in MCF-7 breast cancer cells when using a doxorubicin formulated PEG-b-PCL micelle system in comparison to free doxorubicin.41 The confocal microscopy images showed that the micelle-incorporated doxorubicin resides in the cytoplasm, and free doxorubicin accumulates quickly in the cell nucleus. The delayed cell death could be due to the difference in the subcellular localization of free and micellized drug because doxorubicin can only exert its cytotoxic effect after reaching the nucleus.41 Interestingly, as reported by Yoo and Park, doxorubicin-conjugated PEG-b-PLGA micelles, led to a 10-fold increase in the cytotoxicity of this drug. However, in this case, doxorubicin was found to localize in both the cytoplasm and the nucleus when delivered by micelles.77 The discrepancy between the intracellular localization of doxorubicin formulated in the two distinct systems may be explained by their different drug release profiles. The PCL core is more...

Plga Nanoparticles For Gene Delivery To Cancer

Although various polymeric systems are under investigation,40 our efforts are focused on investigating biodegradable nanoparticles as a gene delivery system in cancer therapy.19,41-43 These nanoparticles are formulated using PLGA and PLA polymers, with plasmid DNA (pDNA) entrapped into the nanoparticle matrix. The main advantage of PLGA or PLA-based nanoparticles for gene delivery is their non-toxic nature. Furthermore, the slow release of the encapsulated DNA from nanoparticles is expected to provide sustained gene delivery (Figure 14.2a). Blends of PLGA and polyoxyethylene derivatives such as poloxamer and poloxamine are also being used to modulate DNA release from nanoparticles.44 In our study we demonstrated anti-proliferative activity of wild-type (wt) p53 gene-loaded nanoparticles in breast cancer cell line.45 Cells trans-fected with wt-p53 DNA-loaded nanoparticles demonstrated sustained and significantly greater anti-proliferative effect than those treated with naked wt-p53 DNA...

Committee Biographies

Mowery is the William A. and Betty H. Hasler Professor of New Enterprise Development at the Walter A. Haas School of Business at the University of California, Berkeley, a research associate of the National Bureau of Economic Research, and during the 2003-2004 academic year was the Bower Fellow at the Harvard Business School. He received his undergraduate and Ph.D. degrees in economics from Stanford University and was a postdoctoral fellow at the Harvard Business School. Dr. Mowery taught at Carnegie Mellon University, worked as a staff officer for the National Academies, and served in the Office of the United States Trade Representative as a Council on Foreign Relations' International Affairs Fellow. He has been a member of a number of NRC committees, including those on the Competitive Status of the U.S. Civil Aviation Industry, on the Causes and Consequences of the Internationalization of U.S. Manufacturing, on the Federal Role in Civilian Technology Development, on U.S....

Combination Of Pgtxl With Radiotherapy

Combining chemotherapy and radiotherapy has significantly improved response and survival rates in patients with many solid tumors. Many chemotherapeutic agents can increase the radiosensitivity of tumors, potentiating the tumor response to radiation-caused damage. It was hypothesized that combining radiotherapy and chemotherapy using a polymer-drug conjugate may lead to a stronger radiosensitizing effect than using the drug alone. Irradiation can, in turn, potentiate the tumor response to polymer-drug conjugates by increasing tumor vascular permeability and the uptake of these conjugates into solid tumors. To test this hypothesis, PG-TXL was used as a model polymer-drug conjugate.58 Administration of PG-TXL delayed the growth of OCa-1 syngeneic murine ovarian tumors in C3Hf Kam mice. However, when PG-TXL was given in combination with tumor irradiation, significantly enhanced anti-tumor activity was observed. Using tumor growth delay as an end point, enhancement factors ranging from...

Nanoparticles For Drug Delivery

The majority of the chemotherapeutic agents used in cancer therapy are low molecular weight drugs with a high volume of distribution, leading to the presence of toxic compounds throughout the body. These drugs must be given in high doses in order to reach therapeutic levels in tumor tissues. In the process, healthy tissues are exposed to cytotoxic drugs, resulting in side effects such as bone marrow suppression, alopecia, anorexia, etc. The low molecular weight anti-cancer agents are also rapidly cleared from the body. Continuous treatment of tumor cells with these drugs would exacerbate the problem of MDR that is one of the main reasons for the failure of chemotherapy.19 Numerous efforts in improving cancer chemotherapy have focused on increasing the therapeutic index and reducing the non-selective cytotoxicity of the drugs in use. Macromolecular carriers such as polymer conjugates, liposomes, microspheres, and nanoparticles are used for this purpose. Of these, the nanoparticles have...

Cancer Treatment with Diamonds

Developed originally for the surface finishing industry, diamond nanoparticles are finding new and far-reaching applications in modern biomedical science and biotechnologies. Because of its excellent biocompatibility, diamond has been called the biomaterial of the 21st century and medical diamond coatings are already heavily researched for implants and prostheses. Nanoscale diamond is being discussed as a promising cellular biomarker and a nontoxic alternative to heavy-metal quantum dots. Further extending the nanomedical use of diamond, researchers have demonstrated a nanodiamond-embedded device that could be used to deliver chemotherapy drugs locally to sites where cancerous tumors have been surgically removed. ''Our work has shown that nanodiamonds serve as versatile platforms that can be embedded within polymer-based microfilm devices,'' Dean Ho tells us. ''The nanodiamonds are complexed with a chemotherapeutic agent, and subsequently enable sustained, slow release of the drug for...

Influence or Effect on Multi Drug Resistance

Multi-drug resistance (MDR) is one of the most significant obstacles in chemotherapy and is often found in refractory cancers. MDR may be a result of the undesired efflux of a drug from the intracellular compartment. Transporter proteins that are overexpressed on the cell membrane of certain cancer cells are responsible for drug efflux. The drug efflux protein that has been studied most extensively is the ATP-dependent P-glycoprotein (P-gp).26,123 This drug transporter is also expressed in healthy tissues such as the epithelial cells of the intestine and the endothelial cells in the blood-brain barrier. The normal physiological function of P-gp is to regulate molecular transport and provide protection or detoxification of the cell.124 The normal physiological levels of drug efflux protein also function to limit the bioavailability of drugs delivered via the oral route as well as to limit drug delivery to the brain. In many of the studies, the P85 copolymer was fundamental in the...

Polymer Based Nuclear Imaging and Radiotherapy

With the appropriate delivery system, radioisotopes have a significant advantage over other therapy agents, namely, the emission of energy that can kill at a distance from the point of radioisotope localization. This diameter of effectiveness helps to overcome the problem of tumor heterogeneity because, unlike other molecular therapy (cell toxins, chemotherapy, etc.), not all tumor cells need to take up the radioisotope to eradicate a tumor. There are also physical characteristics (type of particle emission, emission energy, half-life) of different radioisotopes that may be selected to enhance therapeutic effectiveness.174 For example, different isotopes deliver beta particulate ionization over millimeters (131I) to centimeters (90Y). Long-lived isotopes such as 131I that remain within the tumor target may provide extended radiation exposure and high radiation dose, especially if there is progressive renal clearance and high target to non-target ratios.

Sources of Ethical Behavior

It is important to recognize that there are sins of omission as well as commission. To fail to develop a beneficial nanotechnology application could also be unethical. Imagine, for instance, that a laboratory had discovered how nanotechnology could enable a much more effective form of chemotherapy to cure cancer reliably and cheaply, but the company owning the patents prevented it from being developed, because its less effective traditional chemotherapy products were more profitable. This could be considered just as unethical as doing aggressive harm.

Drug Delivery to Resistant Tumor Cells

Several cancers show resistance to conventional chemotherapy. Resistance to cancer chemotherapy involves both altered drug activity at the designated target and modified intra-tumor pharmacoki-netics (e.g., uptake and metabolism). The membrane transporter P-glycoprotein plays a major role in pharmacokinetic resistance by preventing sufficient intracellular accumulation of several anticancer agents. Inhibiting the P-glycoprotein has great potential to restore chemotherapeutic effectiveness.136 PACA nanoparticles were found to overcome multi-drug resistance (MDR) phenomena

Drug Delivery to Lymphatic Carcinomas

The lymphatic system is the physiological system that maintains the body water balance. It also controls certain immunological responses. At times, this system acts as a medium for the mestastais of cancer cells. Due to the peculiarity of the anatomy of the lymphatic interstitium, the achievement of drug localization into the lymphatic system is limited. Much effort has been made to achieve lymphatic targeting of drugs using colloidal carriers such as biodegradable nanoparticulate systems, including nanospheres, emulsions, and liposomes.175 The major purpose of lymphatic targeting is (1) to provide an effective anti-cancer chemotherapy that will prevent the metastasis of tumor cells by accumulating the drug in the regional lymph node, and (2) to enhance the localization of diagnostic agents in the regional lymph node to visualize the lymphatic vessels before surgery. In the early days of lymphatic-targeting research, some success was achieved in delivering the emulsions and liposomes...

Ultrasonic Irradiation

The application of ultrasonic irradiation at tumor sites has been found to be effective in enhancing the accumulation of drugs in tumor cells and has resulted in improved therapeutic efficacy. The use of ultrasonic irradiation for micelle-based chemotherapy can be optimized by varying many factors including the sonication frequency, the types of waves applied, the time between drug injection and the application of ultrasound as well as the physico-chemical properties of the micelles.150,151 Micelle properties such as the hydrophobicity and state of the micelle core were found to be the The application of ultrasound perturbs the drug-loaded micelles, shifting the equilibrium from micelle-encapsulated drug to free drug. In this way, the release of drugs from the micelles is triggered.151,152 Furthermore, ultrasonication can cause reversible cell membrane disruption, creating temporary pores in the membrane, resulting in enhanced drug diffusion into the cells following drug release.119...

Second Generation Inhibitors

Even so, two new directions in the inhibition of methyltransferases are being explored. Both first-generation inhibitors of DNA methyltransferase (32) and second-generation inhibitors of methyl-transferase action are under study (37-41). The use of second-generation inhibitors should avoid the side effects produced by the necessity of random incorporation into DNA required for decitabine action because second-generation inhibitors are DNA analogs that act as direct inhibitors of the methyltransferase (38,40,42,43).

Drug Delivery to Brain Tumors

Brain tumors are one of the most lethal forms of cancer. Many primary brain tumors are most resistant to chemotherapy, probably due to the presence of a tight BBB.162 They are extremely difficult to treat due to a lack of therapeutic strategies capable of overcoming barriers for effective delivery of drugs to the brain. In fact, the vasculature of gliomas possess some special features open endothelial gaps (inter-endothelial junctions and transendothelial channels having diameter of about 0.3 mm), fenestrations (5.5 nm maximum width), cytoplasmic vesicles such as caveolae (5070 nm diameter), and vesicular vacuolar organelles (108 + 32 nm diameter). All of these features are due to the secretion of a vascular endothelial growth factor (VEGF) that causes the loss of the barrier function of BBB, which is essential for delivering drugs to the brain.163 Nanoparticles are considered suitable for delivering drugs to the brain, but they should possess the following ideal characteristics 164...

Wireless Medical Monitor Advantages and Disadvantages The Concept

A wireless physiological measurement system measures in real-time, a bio-signal for local processing (Hao and Foster 2008). A good example is an automatic internal cardiac defibrillator (AICD, also known as an implantable cardioverter defibrillator or ICD), which acts to restore the regular heart rhythm by delivering an electric shock if abnormal behavior is detected, potentially averting sudden cardiac death (Hao and Foster 2008). Another example is implantable drug delivery systems, which deliver medication more efficiently for chemotherapy, pain management, diabetic insulin delivery, and AIDS therapy, by locally processing wireless physiological measurements (Jones et al. 2006).

Aptamerdrug Conjugates For Targeted Cancer Therapy

For the preparation of the aptamer-drug conjugates, conventional conjugation strategies that have been used for the preparation of immunoconjugates may also be employed with some modifi-cations.125 For targeted radiotherapy, beta-emitting radioisotopes, such as 131I, 90Y, or 67Cu, or alpha-emitting radioisotopes such as 213Bi or 211At, may be used to develop radioaptamerconju-gates. These radioisotopes may be linked directly to aptamers or immobilized through metal chelators attached to aptamers. For targeted chemotherapy, drug molecules (i.e., doxorubicin, calicheamicin, or auristatin) may be covalently coupled to one or more sites on the aptamer using simple chemistry (i.e., formation of amide, disulfide, or hydrazone bond).134,135 The development of aptamer conjugates is facilitated by site-selective functionalization of aptamers at their 3'-and or 5'-terminus, making it possible to reproducibly attach an exact number of drugs in a site-

Applications of Magnetic Nanocomposites

Fe5o7 Light Absorbtion

In the area for cancer treatment, a relatively non-specific feature of chemotherapy is one of its major disadvantages. The therapeutic drugs are administered intravenously leading to general systematic distribution, resulting in deleterious side effects as the drug attacks normal, healthy cells in addition to the target tumor cells. However, if such treatments could be localized or brought exactly to the affected site, then the continued use of very potent and effective agents could be made possible. This was probably the main impetus to recognize the purpose to use magnetic carriers to target specific sites (generally cancerous tumors) within the body. In magnetically targeted therapy, a cytotoxic drug is attached to a biocompatible magnetic nanoparticle carrier 46 . The PMAA coated maghemite nanoparticles are recognized as potential magnetically targeted drug carriers by adsorbing an anticancer drug (carboplatin) by virtue of the ion-dipole interaction between CO.- of PMAA and...

In VitroIn Vivo Studies

The progress in the development of biodegradable nanoparticulate systems, including nanospheres, emulsions, and liposomes, was reviewed 952 . The major purpose of lymphatic targeting was to provide an effective anticancer chemotherapy to prevent the metastasis of tumor cells by accumulating the drug in the regional lymph node via subcutaneous administration. The objectives of lymph targeting involved the localization of diagnostic agents to the regional lymph node to visualize the lymphatic vessels before surgery, and the improvement of peroral bioavailability of macromolecular drugs, like polypeptides or proteins. The

Chemoembolization Using Alkylcyanoacrylates

HCC is the most common liver tumor, with heterogeneity in the tumor behavior and the underlying liver disease. Recent combinations such as cisplatin, interferon, Adriamycin, and 5-FU are extremely toxic and yield response rates of only 20 , with no survival advantage compared to supportive care alone.184 Higher concentrations of cancer chemotherapeutic agents can be delivered directly to the HCC via the hepatic arterial route. Considering that this route is the major vascular supply of these tumors, an even larger number of papers have reported the experience of hepatic artery chemotherapy or hepatic artery chemoembolization (TACE) with single agents, or with a dizzying combination of agents, and at doses not replicated by any two institutions. Loewe et al.185 evaluated the potential of transarterial permanent embolization with the use of a mixture of cyanoacrylate and lipiodol for the treatment of unresectable primary HCC. Loewe et al.186 used NBCA for hepatic artery embolization for...

Nanotherapeutic Devices in Oncology

The economic burden imposed by cancer is immense, measuring in the billions of dollars annually in the United States alone. Existing therapies such as surgical resection, radiotherapy, and chemotherapy have profoundly limited efficacy and frequently provide unfavorable outcomes as the result of catastrophic therapeutic side effects. Additionally, the biology, chemistry, and physics of cancer, in general, and solid tumors in particular, provide therapeutic avenues accessible only by nanoscale therapeutics. Oncology is thus an ideal arena for emerging nanotechnological therapies.

Harnessing Nanotechnology for Sustainable Development

This is the beginning of a new paradigm for healthcare. Lack of accurate, affordable and accessible diagnostic tests impedes global health efforts, especially in the remote and inaccessible regions of the world. Many communicable diseases like HIV AIDS, malaria, tuberculosis and others can be diagnosed with the help of screening devices using nanotechnology. The standard diagnostic tests for these diseases in the developing world are costly, complex, and poorly suited to resource-limited settings. A radically new approach to health diagnosis has been developed in India by the Central Scientific Instruments Organisation (CSIO). Theoretical simulation and design parameters for a micro-diagnostic kit using nano-sized biosensors were completed in 2004 and are ready for clinical trials (Ref 26). The techniques are based on highly selective and specific biosensors and receptors like antibodies, antigens and DNA, which enable an early and precise diagnosis of various diseases. The diagnostic...

Implantable devices including sensing devices implantable medical devices and sensory aids

Implantable sensors can be engineered to work with medical devices to automatically administer treatments for a variety of conditions. Implantable microfluidic systems are being developed to dispense drugs on demand. Initial applications of these systems will likely include delivery of chemotherapy drugs for oncology patients and the delivery of drug treatments for patients suffering from a variety of diseases including, autoimmune disorders, human immunodeficiency virus acquired immunodeficiency syndrome (HIV AIDS) and diabetes. Implantable sensors that monitor heart rate can also act as a defibrillator to regulate irregular rhythms.

R857n34n36 2006

The new advances in biotechnology, genetic engineering, genomics, proteomics, and medicine will depend on how well we master nanotechnology in the coming decades. Nanotechnology could provide the tools to study how the tens of thousands of proteins in a cell (the so-called proteome) work together in networks to orchestrate the chemistry of life. Specific genes and proteins have been linked to numerous diseases and disorders, including breast cancer, muscle disease, deafness, and blindness. Protein misfolding processes are believed to cause diseases such as Alzheimer's disease, cystic fibrosis, mad cow'' disease, an inherited form of emphysema, and many cancers.

Biochips

The application of a biochip using the molecular beacon (MB) detection scheme has been reported Culha et al, 2004 . The medical application of this biochip novel MB detection system for the analysis of the breast cancer gene BRCA1 was illustrated. The MB is designed for the BRCA1 gene and a miniature biochip system is used for detection. The detection of BRCA1 gene is successfully demonstrated in solution and the limit of detection (LOD) is estimated as 70 nM.

Safety Issues

Although generalizations can be made for a particular targeted nanoparticle delivery system, specific issues will arise for each type of payload it contains and for each indication. It will be important to balance potential safety concerns for using nanoparticles with their potential benefits for reducing a safety concern that occurs without their use for comparable (or even improved) efficacy. Nanoparticles can tremendously reduce toxicity by sequestering cytotoxic materials from non-specific tissues and organs of the body until reaching the cancer site.59 Polymeric nanoparticles have been loaded with tamoxifen for targeted delivery to breast cancer cells to improve the efficacy to safety quotient relative to direct administration of this cytotoxic agent.60 Coupling of doxoru-bicin-loaded liposomes to antibodies or antibody fragments that can enhance targeting to cancer cells appears quite promising as a means of further improving the efficacy to toxicity profile for this...

Baldness

Lest anyone argue that hair restoration is an impossible dream, it might be well to mention that not all hair loss is permanent, even now. Chemotherapy and various medical conditions can cause complete hair loss, which reverses itself when the therapy is discontinued or the condition is corrected. And it seems intuitively reasonable that a nanomachine working from inside the hair follicle, right where the action is, should have a better chance of success than any amount of medication trying to fight its way in from outside the scalp.

Figure I9

There are also numerous biological applications being investigated for nanotechnology, including such devices that may provide very early cancer detection by being specially engineered to bind to molecules associated with cancer. Other devices may be used to deliver carefully controlled doses of chemotherapy agents directly to the cancer cells to be destroyed, relieving cancer patients of the need to undergo the widespread poisoning of their bodies associated with conventional chemotherapy. In other medical areas, there have been suggestions that fullerenes may be used to interfere with the ability of human immunodeficiency virus (HIV) to reproduce, offering a potential treatment for AIDS. These kinds of inventions may be entitled to special treatment by the patent office because they are related to HIV AIDS or to cancer.

Therapeutic Payloads

Liposomes have been the most extensively utilized nanoparticle-based carriers for delivering anti-cancer drugs. First described decades ago, these submicron-sized carriers consist of amphiphilic lipids assembled to form vesicles that can encapsulate drugs.76 Liposome-encapsulated doxorubicin is a clinically approved nanoparticle formulation used for chemotherapy.77 The surface of this nanocarrier is PEGylated to reduce rapid uptake by phagocytic cells and extend the drug circulation time for better therapeutic efficacy. Several other liposome-encapsulated chemotherapeutic drugs have been described, with many in clinical trials.78 Active targeting of these liposomes through the attachment of antibodies and various ligands has also been demonstrated.30,79 Drug loaded liposomes with encapsulated or surface-functionalized gadolinium or fluorophores have been used to simultaneously image tumors during nanoparticle-targeted drug delivery.80-82

October 17 2000

Photodynamic therapy (PDT) uses light-activated drugs and non-thermal light to achieve selective, photochemical destruction of cancer cells with minimal effect on surrounding normal tissues. C Sixty has developed fullerene-based photodynamic agents for the treatment of cancer. C Sixty's photodynamic compounds compare favorably with existing treatment methods for cancer such as surgery, radiation, and chemotherapy, and suggest cost-effectiveness, important in today's managed care environment. C Sixty Inc.'s proprietary drugs for photodynamic therapy have been successful in pre-clinical animal studies demonstrating tumor regression with no significant toxicity.

Nanoshells

Nanoshells are currently being investigated as a treatment for cancer similar to chemotherapy but without the toxic side effects. These nanoshells can be injected safely into the body as demonstrated in animal tests. Once in the body, the nanoshells are illuminated with a laser beam that gives off intense heat that destroys the tumor cells.

Angiogenesis Markers

The identification of angiogenesis markers has spurred the development of technologies to enhance early cancer diagnosis, therapy planning, and therapeutic intervention. The development of diagnostic agents is mainly focused in the areas of nuclear scintigraphy, MRI, and near-infrared (NIR) imaging using matrix metalloproteinase (MMP) inhibitors and aVb3 integrin antagonists (Table 9.2).19,20,51,52 Tumor vascular targeting peptides have been used to deliver chemotherapy (Table 9.3) given that they selectively target tumor angiogenesis53,54 and are internalized once bound to cell surface receptors.55,56 The most important classes of angiogenic targets and pertinent imaging and therapy studies are briefly discussed below.

Integrins

RGD-targeted prodrugs have been tested as a means to improve chemotherapy toxicity profiles (Table 9.3). One strategy utilizes an enzymatically cleavable tripeptide sequence (D-Ala-Phe-Lys) recognized by the tumor-associated protease, plasmin, as a linker between RGD4C and doxorubicin.130 Upon incubation with plasmin in vitro, doxorubicin is released and regains its cytotoxicity for endothelial and fibrosarcoma cells. Toxicity studies in BALB c and nude mice showed significantly higher weight loss and mortality for free doxorubicin relative to an equimolar dose of the prodrug.131 Furthermore, in vivo evaluation in mouse breast cancer and human adenocarcinoma models showed that prodrug anti-tumor efficacy was associated with strong inhibition of angiogen-esis.131 A similar RGD4C-doxorubicin conjugate was tested in an aVb3 negative murine hepatoma model and was found to have superior anti-tumor effectiveness as compared to free doxorubicin.132

Active Targeting

FIGURE 17.7 (See color insert following page 522.) Confocal fluorescence microscopy image of epidermal growth factor receptor (EGFR)-overexpressed breast cancer cells (MDA-MB-468) following incubation with EGF-conjugated poly(ethylene glycol)-block-poly(S-valerolactone) micelles (as shown in red) for 2 h at 37 C. The cell nuclei are stained with Hoechst 33258 (blue). The EGF-conjugated micelles mainly localized at the perinuclear region as well as within the nucleus as shown by the white arrows. FIGURE 17.7 (See color insert following page 522.) Confocal fluorescence microscopy image of epidermal growth factor receptor (EGFR)-overexpressed breast cancer cells (MDA-MB-468) following incubation with EGF-conjugated poly(ethylene glycol)-block-poly(S-valerolactone) micelles (as shown in red) for 2 h at 37 C. The cell nuclei are stained with Hoechst 33258 (blue). The EGF-conjugated micelles mainly localized at the perinuclear region as well as within the nucleus as shown by the white...

Multidrug Resistance

We have exploited the optical detection sensitivity and the high resolution of NSOM to detect the cellular localization and effect of ABC proteins associated with MDR 24-26 . Drug resistance can be associated with several cellular mechanisms ranging from reduced drug uptake to reduction of drug sensitivity due to genetic alterations. MDR is therefore a phenomenon that indicates a variety of strategies that cancer cells are able to develop in order to resist the cytotoxic effects of anticancer drugs. Decades of studies demonstrate that there are different ways in which tumor cells can develop resistance. MDR can result from (1) decreased influx of cytotoxic drugs 27 , (2) overexpression of drug transporters that belong to the ABC family of proteins including the Pgp, MDR-associated protein (MRP1), and the breast cancer resistance protein 1 (BCRP1), and (3) changes in cellular physiology affecting the structure of the plasma membrane, the cytosolic pH, and the rate and extent of...

Hyperthermia

Very simply stated, hyperthermia is the application of concentrated therapeutic heat to treat cancer. Due to its increasingly impressive research and clinical track records, it is considered as main-stream as surgery, chemotherapy, and radiation, and is now recognized as the fourth modality in approved cancer treatment. However, due to its relatively recent acceptance in major medical circles, it is not well known - yet it is a treatment with genuine promises. A large body of medical evidence shows that when hyperthermia is used in combination with radiation therapy or chemotherapy, there is a dramatic improvement in response rates 222 . Since the heat generated is used to destroy the cancerous tissue, the primary question is which temperature range has to be chosen for the therapy 223 . According to the various mechanisms of cell damage, one has to differentiate between hyperthermia and thermoablation. Hyperthermia is known to use a moderate temperature elevation (treatments up to...

Controlled release

Many other promising drugs never make it to clinical trials because of inherent pharmacological drawbacks. Low-molecular-weight drugs, such as most chemotherapy drugs, are usually insoluble and highly toxic. Protein and nucleic acid drugs usually have poor stability in physiological conditions. It is therefore essential for these drugs to be protected en route to their target disease sites in the body. Drug-delivery systems may rescue potential drug candidates by increasing solubility and stability.

Conclusion

The targeted delivery of chemotherapeutic drugs for cancer therapy may minimize their side effects and enhance their cytotoxicity to cancer cells, resulting in a better clinical outcome. We anticipate that the combination of controlled release technology and targeted approaches may represent a viable approach for achieving this goal. One major clinical advantage of targeted drug-encapsulated nanoparticle conjugates over drugs that are directly linked to a targeting moiety is that large amounts of chemotherapeutic drug may be delivered to cancer cells per each delivery and biorecognition event. Another advantage would be the ability to simultaneously deliver two or more chemotherapeutic drugs and release each in a predetermined manner, thus resulting in effective combination chemotherapy, which is common for the management of many cancers. Antibodies and peptides have been widely used for the targeted delivery of drug encapsulated nanoparticles however, the translation of these...

Gold Nanoshells

To treat breast cancer cells with gold-coated nanoparticles, for example, antibodies are attached to the gold nanoshells, which latch onto the targeted cancer cells. In tests, mouse cancer cells have been treated by shining an infrared laser beam on an affected area. The gold absorbing the infrared light heats up, but the healthy tissues (with no attached gold nanoparticles) keep cool and are not affected. The rising heat (55 C) fries the tumor cells, leaving healthy cells unharmed. The beauty of this site-specific treatment is that since only the cancerous areas cook, the rest of the body's healthy tissues are not impacted. This offers a huge benefit over chemotherapy, which kills rapidly growing cells, both friend and foe. (One of the main reasons chemotherapy patients lose their hair is because hair follicle cells divide faster than other cells and are slammed by chemotherapy chemicals.) In gold nanoshell treatments with mice, scientists achieved a 100 percent effectiveness rate in...

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