VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients
TL;DR: Platelets sequester angiogenesis regulatory proteins which suggests an avenue for developing biomarkers to monitor disease and Multivariable logistic regression analysis indicated that PDGF, PF4 and VEGF were independent predictors of colorectal carcinoma and as a set provided statistically significant discrimination.
Abstract: Platelets sequester angiogenesis regulatory proteins which suggests an avenue for developing biomarkers to monitor disease. We describe a comparison of angiogenesis regulatory proteins found in platelets of colorectal cancer patients and normal controls. Platelet and plasma content of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), platelet factor 4 (PF4), thrombospondin-1 (TSP-1) and endostatin in 35 patients with colon cancer were compared with 84 age-matched healthy controls using ELISAs. We standardized the platelet preparation procedure, introduced process controls and normalized the respective protein levels to platelet numbers using an actin ELISA. Statistically significant differences were found in the median levels of VEGF, PF4 and PDGF in platelets of patients with cancer compared to healthy individuals. Platelet concentrations in cancer patients versus controls were: VEGF 1.3 versus 0.6 pg/106, PF4 18.5 versus 9.4 ng/106, and PDGF 34.1 versus 21.0 pg/106. Multivariable logistic regression analysis indicated that PDGF, PF4 and VEGF were independent predictors of colorectal carcinoma and as a set provided statistically significant discrimination (area under the curve = 0.893, P < .0001). No significant differences were detected for bFGF, endostatin, or TSP-1. Reference Change Value analysis determined that the differences seen were not clinically significant. Plasma levels yielded no correlations.
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TL;DR: The extrinsic regulation of angiogenesis by the tumour microenvironment is discussed, highlighting potential vulnerabilities that could be targeted to improve the applicability and reach of anti-angiogenic cancer therapies.
Abstract: Tumours display considerable variation in the patterning and properties of angiogenic blood vessels, as well as in their responses to anti-angiogenic therapy. Angiogenic programming of neoplastic tissue is a multidimensional process regulated by cancer cells in concert with a variety of tumour-associated stromal cells and their bioactive products, which encompass cytokines and growth factors, the extracellular matrix and secreted microvesicles. In this Review, we discuss the extrinsic regulation of angiogenesis by the tumour microenvironment, highlighting potential vulnerabilities that could be targeted to improve the applicability and reach of anti-angiogenic cancer therapies.
1,145 citations
TL;DR: Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors and Design Considerations for Tumour-Targeted Nanoparticles.
Abstract: 1.1. Cancer and Early Detection
Cancer is the second most common cause of death in the United States, trailing only heart disease in incidence. Despite significant worldwide investment in research, cancer remains responsible for 1 in 4 deaths in developed countries.1 Globally, over 14 million cancer diagnoses were reported in 2012, a figure expected to increase to over 22 million cases per annum in the next two decades.2 Estimated to kill over 1/2 million U.S. citizens, and with over 1.6 million new cases predicted to be diagnosed this year,3 cancer continues to present a major, yet unmet challenge to healthcare both globally and in the United States.
Cancer emerges from our own tissues, complicating both detection and treatment methods due to the similarities between the diseased tissue and healthy tissue.4,5 Despite this fact, the mortality rate from cancer is often greatly reduced by early detection of the disease. For example, non-small-cell lung cancer is responsible for the most cancer related deaths worldwide, with patients in the advanced stages of the disease having only 5–15% and <2% 5-year survival rates for stage III and IV patients, respectively.6 In contrast, patients who start therapy in the early stages of the disease (stage I) have markedly improved survival rates, with an 80% overall 5-year survival rate.6 Consequently, early diagnosis is essential to improving cancer patient prognosis.
At present, clinical detection of cancer primarily relies on imaging techniques or the morphological analysis of cells that are suspected to be diseased (cytology) or tissues (histopathology). Imaging techniques applied to cancer detection, including X-ray, mammography, computed tomography (CT), magnetic resonance imaging (MRI), endoscopy, and ultrasound, have low sensitivity and are limited in their ability to differentiate between benign and malignant lesions.7,8 While cytology, such as testing for cervical cancer via a Pap smear or occult blood detection, may be used to distinguish between healthy and diseased cells or tissues, it is not effective at detecting cancer at early stages. Similarly, histopathology, which generally relies on taking a biopsy of a suspected tumor, is typically used to probe the malignancy of tissues that are identified through alternative imaging techniques, such as CT or MRI, and may not be used alone to detect cancer in its early stages. As such, the development of assays and methods for early detection of cancer, before the disease becomes symptomatic, presents a major challenge.
Recent research within the field of nanotechnology has focused on addressing the limitations of the currently available methods for cancer diagnosis. Certain nanoparticle probes possess several unique properties that are advantageous for use in the detection of cancer at the early stages. In this review, we will discuss the advances in the development of nanoparticle-based methods for the detection of cancer by fluorescence spectroscopy. We will divide this topic into three categories: techniques that are designed for (1) the detection of extracellular cancer biomarkers, (2) the detection of cancer cells, and (3) the detection of cancerous tissues in vivo. We will discuss these strategies within the context of the nanoparticle probe used as well as the recognition moieties applied in each approach. Ultimately, the translation of these methods from the laboratory to the clinic may enable earlier detection of cancer and could extend patient survival through the ability to administer therapeutic treatment in the early stages of the disease.
While this review provides a comprehensive overview of the nanoparticle probes that are used to detect cancer in vitro and in vivo through fluorescence, there are several other relevant reviews that may be of interest to our readers, who may refer to the references for more generalized reviews of nanomaterials used for diagnostics and therapy,9–12 or more detailed insight into the specific types of nanoparticle probes (i.e., quantum dots,13 gold nanoparticles,14,15 upconversion nanoparticles,16 polymer dots,17,18 silica nanoparticles,19 polymeric nanoparticles, 20 etc.) for cancer diagnosis.
808 citations
TL;DR: The basic scientist studying platelet function can think beyond the traditional hemostasis and thrombosis paradigms, while the practicing hematologist must appreciate platelet relevance in a wide range of disease processes.
450 citations
Cites background from "VEGF, PF4 and PDGF are elevated in ..."
...Relevant to this release is the reported increase in the stored platelet content of VEGF, platelet factor 4, and PDGF of patients with colorectal cancer.(68) Increased levels of platelet microparticles are found in the plasma of patients with both solid tumors and hematologic malignancies....
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TL;DR: Evidence supporting a mechanistic explanation for the improved activity of cancer chemotherapy when administered on a metronomic, rather than an MTD schedule is presented and the implications of these findings for further translation into the clinic are discussed.
177 citations
TL;DR: Depending on the underlying pathology, platelets can enhance or diminish leukocyte cytokine production, indicating that platelet-leukocyte interactions represent a fine balanced system to restrict excessive inflammation during infection.
Abstract: Beyond their traditional role in haemostasis and thrombosis, platelets are increasingly recognised as immune modulatory cells. Activated platelets and platelet-derived microparticles can bind to leukocytes, which stimulates mutual activation and results in rapid, local release of platelet-derived cytokines. Thereby platelets modulate leukocyte effector functions and contribute to inflammatory and immune responses to injury or infection. Platelets enhance leukocyte extravasation, differentiation and cytokine release. Platelet-neutrophil interactions boost oxidative burst, neutrophil extracellular trap formation and phagocytosis and play an important role in host defence. Platelet interactions with monocytes propagate their differentiation into macrophages, modulate cytokine release and attenuate macrophage functions. Depending on the underlying pathology, platelets can enhance or diminish leukocyte cytokine production, indicating that platelet-leukocyte interactions represent a fine balanced system to restrict excessive inflammation during infection. In atherosclerosis, platelet interaction with neutrophils, monocytes and dendritic cells accelerates key steps of atherogenesis by promoting leukocyte extravasation and foam cell formation. Platelet-leukocyte interactions at sites of atherosclerotic lesions destabilise atherosclerotic plaques and promote plaque rupture. Leukocytes in turn also modulate platelet function and production, which either results in enhanced platelet destruction or increased platelet production. This review aims to summarise the key effects of platelet-leukocyte interactions in inflammation, infection and atherosclerosis.
174 citations
References
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Book•
15 Jun 2006
TL;DR: Practical Statistics for Medical Research is a problem-based text for medical researchers, medical students, and others in the medical arena who need to use statistics but have no specialized mathematics background.
Abstract: Most medical researchers, whether clinical or non-clinical, receive some background in statistics as undergraduates. However, it is most often brief, a long time ago, and largely forgotten by the time it is needed. Furthermore, many introductory texts fall short of adequately explaining the underlying concepts of statistics, and often are divorced from the reality of conducting and assessing medical research.
Practical Statistics for Medical Research is a problem-based text for medical researchers, medical students, and others in the medical arena who need to use statistics but have no specialized mathematics background.
The author draws on twenty years of experience as a consulting medical statistician to provide clear explanations to key statistical concepts, with a firm emphasis on practical aspects of designing and analyzing medical research. The text gives special attention to the presentation and interpretation of results and the many real problems that arise in medical research
17,322 citations
"VEGF, PF4 and PDGF are elevated in ..." refers methods in this paper
...Biomarker levels were normalized to actin levels, expressed per 10(6) platelets and shown graphically using box-and-whisker plots [14]....
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11,536 citations
TL;DR: In this paper, a procedure for determining statistically whether the highest observation, lowest observation, highest and lowest observations, or more of the observations in the sample are statistical outliers is given.
Abstract: Procedures are given for determining statistically whether the highest observation, the lowest observation, the highest and lowest observations, the two highest observations, the two lowest observations, or more of the observations in the sample are statistical outliers. Both the statistical formulae and the application of the procedures to examples are given, thus representing a rather complete treatment of tests for outliers in single samples. This paper has been prepared primarily as an expository and tutorial article on the problem of detecting outlying observations in much experimental work. We cover only tests of significance in thii paper.
3,551 citations
"VEGF, PF4 and PDGF are elevated in ..." refers methods in this paper
...The variability of sample results was assessed in terms of the coefficient of variation and possible outliers were identified by Grubb’s test [13]....
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TL;DR: Angiogenesis research will probably change the face of medicine in the next decades, with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments.
Abstract: The growth of blood vessels (a process known as angiogenesis) is essential for organ growth and repair. An imbalance in this process contributes to numerous malignant, inflammatory, ischaemic, infectious and immune disorders. Recently, the first anti-angiogenic agents have been approved for the treatment of cancer and blindness. Angiogenesis research will probably change the face of medicine in the next decades, with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments.
3,300 citations
Book•
13 Mar 2003
TL;DR: A comparison of Binary Tests and Regression Analysis and the Receiver Operating Characteristic Curve shows that Binary Tests are more accurate than Ordinal Tests when the Receiver operating characteristic curve is considered.
Abstract: 1. Introduction 2. Measures of Accuracy for Binary Tests 3. Comparing Binary Tests and Regression Analysis 4. The Receiver Operating Characteristic Curve 5. Estimating the ROC Curve 6. Covariate Effects on Continuous and Ordinal Tests 7. Incomplete Data and Imperfect Reference Tests 8. Study Design and Hypothesis Testing 9. More Topics and Conclusions References/Bibliography Index
2,289 citations
"VEGF, PF4 and PDGF are elevated in ..." refers methods in this paper
...Accuracy of each biomarker in differentiating cancer patients from controls was evaluated by receiver-operating characteristic (ROC) curve analysis with area under the curve (AUC) with the Youden index used to identify optimal cutoff values [15]....
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