Clinical Proteomics: From Biomarker Discovery and Cell Signaling Profiles to Individualized Personal Therapy

2005 ◽  
Vol 25 (1-2) ◽  
pp. 107-125 ◽  
Author(s):  
Katherine R. Calvo ◽  
Lance A. Liotta ◽  
Emanuel F. Petricoin
Keyword(s):  
Information Flow ◽  
Biomarker Discovery ◽  
Ex Vivo ◽  
Early Stage ◽  
Clinical Proteomics ◽  
Disease Detection ◽  
Early Disease ◽  
Early Stage Disease ◽  
Early Disease Detection ◽  
Highly Sensitive

The discovery of new highly sensitive and specific biomarkers for early disease detection and risk stratification coupled with the development of personalized “designer” therapies holds the key to future treatment of complex diseases such as cancer. Mounting evidence confirms that the low molecular weight (LMW) range of the circulatory proteome contains a rich source of information that may be able to detect early stage disease and stratify risk. Current mass spectrometry (MS) platforms can generate a rapid and high resolution portrait of the LMW proteome. Emerging novel nanotechnology strategies to amplify and harvest these LMW biomarkers in vivo or ex vivo will greatly enhance our ability to discover and characterize molecules for early disease detection, subclassification and prognostic capability of current proteomics modalities. Ultimately genetic mutations giving rise to disease are played out and manifested on a protein level, involving derangements in protein function and information flow within diseased cells and the interconnected tissue microenvironment. Newly developed highly sensitive, specific and linearly dynamic reverse phase protein microarray systems are now able to generate circuit maps of information flow through phosphoprotein networks of pure populations of microdissected tumor cells obtained from patient biopsies. We postulate that this type of enabling technology will provide the foundation for the development of individualized combinatorial therapies of molecular inhibitors to target tumor-specific deranged pathways regulating key biologic processes including proliferation, differentiation, apoptosis, immunity and metastasis. Hence future therapies will be tailored to the specific deranged molecular circuitry of an individual patient's disease. The successful transition of these groundbreaking proteomic technologies from research tools to integrated clinical diagnostic platforms will require ongoing continued development, and optimization with rigorous standardization development and quality control procedures.

scholarly journals Physiological and behavioral responses as indicators for early disease detection in dairy calves

2019 ◽  
Vol 102 (6) ◽  
pp. 5389-5402 ◽  
Author(s):  
G.L. Lowe ◽  
M.A. Sutherland ◽  
J.R. Waas ◽  
A.L. Schaefer ◽  
N.R. Cox ◽  
...  
Keyword(s):  
Behavioral Responses ◽  
Dairy Calves ◽  
Disease Detection ◽  
Early Disease ◽  
Early Disease Detection

scholarly journals Proteomics as a Tool for Biomarker Discovery

2007 ◽  
Vol 23 (5-6) ◽  
pp. 411-417 ◽  
Author(s):  
Elise C. Kohn ◽  
Nilofer Azad ◽  
Christina Annunziata ◽  
Amit S. Dhamoon ◽  
Gordon Whiteley
Keyword(s):  
Quality Improvement ◽  
New Technologies ◽  
Biomarker Discovery ◽  
Early Stage ◽  
Life Quality ◽  
Early Stage Disease ◽  
Novel Technologies ◽  
True Value ◽  
Stage Disease ◽  
New Biomarkers

Novel technologies are now being advanced for the purpose of identification and validation of new disease biomarkers. A reliable and useful clinical biomarker must a) come from a readily attainable source, such as blood or urine, b) have sufficient sensitivity to correctly identify affected individuals, c) have sufficient specificity to avoid incorrect labeling of unaffected persons, and d) result in a notable benefit for the patient through intervention, such as survival or life quality improvement. Despite these critical descriptors, the few available FDA-approved biomarkers for cancer do not completely fit this definition and their benefits are limited to a small number of cancers. Ovarian cancer exemplifies the need for a diagnostic biomarker of early stage disease. Symptoms are present but not specific to the disease, delaying diagnosis until an advanced and generally incurable stage in over 70% of affected women. As such, diagnostic intervention in the form of oopherectomy can be performed in the appropriate at-risk population if identified such as with a new accurate, sensitive, and specific biomarker. If early stage disease is identified, the requirement for survival and life quality improvement will be met. One of the new technologies applied to biomarker discovery is tour-de-force analysis of serum peptides and proteins. Optimization of mass spectrometry techniques coupled with advanced bioinformatics approaches has yielded informative biomarker signatures discriminating presence of cancer from unaffected in multiple studies from different groups. Validation and randomized outcome studies are needed to determine the true value of these new biomarkers in early diagnosis, and improved survival and quality of life.

Expression of the Cancer-Testis Antigens, SEMG 1 and Protamine 1, in Early CLL: Their Relationship to Disease Stage and Zap 70 Expression.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4680-4680
Author(s):  
Farouk Meklat ◽  
Yana Zhang ◽  
Zhiqing Wang ◽  
Jian Zhang ◽  
Sukhrob Mustalov ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Tumor Vaccine ◽  
Early Stage ◽  
Disease Stage ◽  
Early Disease ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Ct Antigen ◽  
Cancer Testis ◽  
Protamine 1

Abstract Despite advances in modern chemotherapy, CLL remains incurable. CLL is an indolent disease. It expresses a panel of Cancer-Testis (CT) antigens. CLL leukemia cells are susceptible to the cytotoxicity of T cells. CLL is, therefore, an ideal disease for immunotherapeutic approaches. Immunotherapy, in addition to being less toxic and more specific than chemotherapy, provides a different mode of cytotoxicity that may synergize with that induced by chemotherapeutic agents. Immunotherapy also offers the prospect of inducing immune memory that may be important for long term disease-free survival of patients with CLL. However, there are obstacles that may prevent successful immunotherapy. CLL patients are generally immunosuppressed even before any therapy is given and the immunosuppression increases as the disease progresses. Therefore, any immunotherapeutic approaches for CLL should be aplied in early disease when immunosuppression is least encountered. We previously demonstrated the expression of a CT antigen, SEMG 1, in 3/9 patients with CLL. Furthermore, we also demonstrated that the presence of high titer IgG in the serum of patients expressing SEMG 1, suggesting the in vivo immunogenicity of SEMG 1 in the cancer-bearing autologous host. We have also recently used SEMG 1 as the bait in a yeast two-hybrid system of testicular cDNA library and identified that Protamine 1 is the interacting ligand of SEMG 1 and that Protamine 1 is also a novel CT antigen, suggesting that both SEMG 1 and Protamine 1 may be suitable antigens for tumor vaccine development. However, the expression of SEMG 1 and Protamine 1 in early CLL is unknown. We have in this study set out to determine whether or not SEMG 1 and/or Protamine 1 could be used for the design of tumor vaccine for the targeting of patients with early CLL, in particular, those with poor risk disease, as predicted by Zap 70 expression. Using pairs of sequence-specific primers in RT-PCR on a cohort of CLL (41 Stage 0/I and 6 Stage II/III), we found that SEMG 1 gene is expressed in 24/47 (51%) and Protamine 1 in 16/47 (34%) of CLL patients. Gene expression in most cases was associated with the detection by immunocytochemistry of SEMG 1 and/or Protamine 1 in the CLL cells. The expression frequency of SEMG1 and Protamine 1 in CLL did not appear to differ between early and late stage disease. 19/41 of patients with early stage disease and 5/6 of patients with late disease expressed SEMG 1; 12/41 of patients with early stage disease and 4/6 patients with late disease expressed Protamine 1. Furthermore, the expression of these antigens was equally distributed between Zap 70+ and Zap 70− CLL. SEMG 1 was expressed in 4/6 of Zap 70+ CLL (all 6 had early disease) and 2/9 of Zap 70− CLL (1/8 early disease and 1/1 late disease). Interestingly, although Protamine 1 expression in CLL predicted for SEMG 1 co-expression, only 67% of SEMG 1+ CLL expressed Protamine 1. Our results, therefore, suggest that both SEMG 1 and Protamine 1 are suitable targets for tumor vaccine development for some patients with early CLL, especially those with high risk disease, as predicted by Zap 70 expression.

Early Disease Detection in Wheat Fields using Spectral Reflectance

2003 ◽  
Vol 84 (2) ◽  
pp. 137-145 ◽  
Author(s):  
Cédric Bravo ◽  
Dimitrios Moshou ◽  
Jonathan West ◽  
Alastair McCartney ◽  
Herman Ramon
Keyword(s):  
Spectral Reflectance ◽  
Disease Detection ◽  
Early Disease ◽  
Early Disease Detection
Sign in / Sign up

Export Citation Format

Share Document