Advances in Cancer Research: 109

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Reproduced from Ref. Various nanoparticle systems are being explored for their potential use in bioimaging for cancer diagnosis or treatment because of their unique properties, including their large surface-to-volume ratio, high biocompatibility, facile surface modification, and overall structural robustness. In addition, they have unique optical, magnetic, and electron properties, which make them ideal candidates for signal generation and transduction in the development of sensing systems [ 5 , 6 , 7 , 8 , 12 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Moreover, some nano-sized materials exhibit unique physical properties, such as a proper size, surface charge, stability, shape, and hydrophilicity, which can aid their effective delivery to the desired site.

The delivery of nano-sized agents is affected by the enhanced permeability and retention EPR effect, which is a unique property of solid tumors that is related to their anatomical and pathological differences from normal tissues. This EPR effect leads to the passive accumulation of large molecules and small particles in tumor tissues due to the cut-off size of the leaky vasculature and retention with long circulation times, which is called passive targeting [ 21 , 22 , 23 , 24 , 25 , 26 ].

Main advantages of the PEGylated proteins. PEG is a shielding the protein surface from degradation agents by steric hindrance. Moreover, the increased size of the conjugate decreases the kidney clearance of the PEGylated protein. In addition, positively charged cationic nanoparticles can easily enhance endocytosis or phagocytosis for cell labeling via electrostatic interactions with the negatively charged cellular membrane.

Among bio-imaging techniques, well-tailored superparamagnetic nanocrystals are of great interest for cancer detection via magnetic resonance MR imaging due to their high sensitivity and specificity due to the nanoeffect. Fluorescence and optical imaging techniques are important tools for in vivo and cellular imaging, and they can provide vital information for cancer diagnosis and therapy in its early stages. In particular, for the fluorescence wavelength, near-infrared NIR light is preferred for tissue and in vivo imaging compared to visible light because of its minimal damage to the tissue, which allows deep tissue penetration, and low auto-fluorescence interference due to the reduced scattering of long wavelength photons [ 9 ].

Active targeting, is also called as ligand-mediated targeting, involves utilizing targeting moieties that are anchored on the surface of nanoparticles and form strong interactions with a particular cell surface marker e. A schematic illustration showing methods used for active targeting of nanoparticles. A Antibody-based targeting, B Aptamer-based targeting, and C Ligand-based targeting of nanoparticels.

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Targeting moieties, such as antibodies, peptides Arg-Glyc-Asp RGD , nucleic acids aptamers , and polysaccharides hyaluronan, dextran , lead to enhanced selective delivery and uptake in the target cells, tissues, organs, or subcellular domains and minimize uptake by the RES system [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. Active tumor targeting is more efficient and specific than passive targeting, and can facilitate early cancer detection.

In particular, active tumor-targeted imaging can quantify the target expression through molecular imaging, so it is an indispensable tool in diagnosis and disease management. For example, for the selective detection of tumors expressing a high level of epidermal growth factor receptors EGFR , anti-EGFR antibody-modified nanoparticles are widely used as imaging agents for MR, CT, and optical imaging. CD44 is a cell surface glycoprotein that is overexpressed in breast cancer and gastric cancer stem cells and is associated with cancer growth, migration, invasion, and angiogenesis.

Hyaluronan HA , which is an immune—neutral polysaccharide, forms a specific interaction with CD Angiogenesis appears to be one of the most crucial steps in tumor translation to the metastatic form, in which it is capable of spreading to other parts of the body by degrading the basement membrane and forming a new vascular structure.

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Targeted-molecular imaging of vascular or angiogenesis can provide accurate anatomic details for effective cancer management. Aptamers Apt are short nucleic acid molecules that can bind to target antigens with high affinity and specificity. The tumor microenvironment plays a critical role in tumor initiation, progression, metastasis, and resistance to therapy [ 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ].

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The microenvironment differs from that of normal tissues because of the dynamic network within normal tissues, including blood and lymphatic vessels, extracellular matrix proteins, and both enzyme and immune components. These unique characteristics lead to a matrix remodeling e.

The changes in the physiological characteristics of tumor microenvironments are consistent, regardless of the type of cancer, so it is possible to use these as a universal indicator for cancer detection. Vesicular pH plays a pivotal role in cell metabolism processes, such as proliferation and apoptosis. They fabricated polyaniline-based nanoprobes that exhibited convertible transition states according to the proton concentration as an in situ indicator of the vesicular transport pH [ 58 ].

A Schematic illustration of organic nanoindicator based on polyaniline nanoparticle for the detection of endolysosomal compartments. Synthesis steps of nanoindicator based on polyaniline in mesosilica template when using heterometal nanoparticle IsNP as oxidant. While migrating from endosomes to lysosomes, transition state of polyaniline transferred to emeraldine salt state due to the increment of proton concentration. The tumor pH is usually more acidic than that of normal tissues due to increased aerobic glycolysis, which is called the Warburg effect tumor have a pH of 6.

This can promote tumor metastasis by generating an invasive environment for tearing down the extracellular matrix and for tissue remodeling. Core—shell MnO Mn 3 O 4 urchin-shaped nanoparticles are synthesized via an anisotropic etching process. The manganese ions released from the MnO phase in the low-pH sites within tumor cells lead to an enhanced T1 contrast image for the entire tumor mass. In addition, specific stromal cell-derived proteases, such as matrix metalloproteases MMP , matrix cysteine cathepsins, and serine proteases, are overexpressed in primary tumors.

These proteases induce the epithelial-to-mesenchymal transition EMT and promote invasion and metastasis by degrading the extracellular membrane. Molecular imaging of the activity of proteases has the potential to determine tumor malignancy, guide the development of diagnostic tools, and evaluate the efficacy of treatment Figure 5 A [ 60 ]. MMPs are the most prominent family of proteases associated with tumorigenesis. Their expression and activity are highly enhanced in many types of human cancer and are strongly implicated in advanced cancer states.

Tumor microenvironment-targeted molecular imaging has the potential to provide clinically significant progress. Emerging evidence suggests that microRNAs can also function as a diagnostic biomarker for human cancers because they can act as tumor suppressor genes or oncogenes. Imaging the intracellular distribution of specific miRNAs should provide insight into the mechanisms of metastasis and invasion.

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  • A Schematic illustration of the dual imaging process of anchored proteinase-targetable optomagentic nanoprobes with activatable fluorogenic peptides MNC-ActFP. B Schematic illustration of miRa beacon delivery system for targeted intracellular recognition of miRa based on Hyaluronic acid HA -coated nanocontainers that encapsulate the miRa beacons bHNCs.

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    Current imaging techniques play an important role in enabling the early detection of several diseases, including cancer, due to their ability to locate tumors and assess the tumor activity. However, these techniques are insufficient to provide reliable and accurate information at the disease site, due to their low sensitivity or limits in their spatial resolution Table 1. Computed tomography CT is useful for tumor staging but offers poor soft tissue contrast, with resulting poor sensitivity and specificity in screening.

    Magnetic resonance imaging MRI offers excellent contrast without ionizing radiation but has temporal and financial needs that are likely inconsistent with high-throughput screening. Positron emission tomography PET , which has very high sensitivity, can investigate various molecular and biochemical properties but is more suitable for monitoring the response to therapy than for detecting early lesions due to its limited spatial resolution. Therefore, multimodal imaging, i.

    Recently, various types of hybrid nanoparticles have been used for multimodal imaging by combining the strengths of individual components into single nano-structured systems. As one of the leading cancer treatment centers in the Southeast, Hollings Cancer Center combines the full range of cancer specialties to deliver a higher level of care to the patients we serve.

    Our team of more than 60 sub-specialists — each concentrating on a specific discipline of cancer treatment and care — works with individual patients to develop customized treatment programs that target a broad range of conditions. Our specialists work together as a team, often meeting with patients under the same roof on the same day. We are striving to deliver the highest level of care in the best way possible.

    The heart of our patient care is located in downtown Charleston, SC. Patients may also be seen in oncology clinic locations closer to home. Personalized patient care is at the center of everything we do.

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    And no one tells the story better than our patients themselves. Meet some of our patients and hear about their cancer journey. Patient Stories. Find a Nurse Navigator. Hollings offers resources for patients, families and those interested in learning more about cancer prevention and risk. Patient Resources. Every treatment that has ever made a difference in cancer was once a part of a clinical trial.

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    Arch Gynecol Obstet. J Endocrinol Invest. The diagnostics of colorectal cancer. Contemp Oncol Pozn. CA handle with care.

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    Clin Chem Lab Med. Ballehaninna U, Chamberlain R. Indian J Surg Oncol. Andren Sandberg A. CA 50 and CA in serum as tumor markers for pancreatic cancer: a review of the literature. Acta Chir Scand Suppl. Serum CA as a good prognostic biomarker in patients with bladder cancer.

    Recent Advances in Bioimaging for Cancer Research

    Int J Surg. Urol Int. Study of serum antioxidant capacity and relation with CA and PSA in patients with gastrointestinal tract and prostate tumors. Case Rep Gastroenterol. Elevation of a tumor associated antigen CA levels in patients with rheumatic diseases. J Rheumatol. Elevated CA caused by Hashimoto's thyroiditis: review of the benign causes of increased CA level. High sensitivity and specificity of CA for pancreatic carcinoma in comparison to chronic pancreatitis.