scholarly journals Multianalyte Tests for the Early Detection of Cancer: Speedbumps and Barriers

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Michael A. Tainsky ◽  
Madhumita Chatterjee ◽  
Nancy K. Levin ◽  
Sorin Draghici ◽  
Judith Abrams

It has become very clear that a single molecular event is inadequate to accurately predict the biology (or pathophysiology) of cancer. Furthermore, using any single molecular event as a biomarker for the early detection of malignancy may not comprehensively identify the majority of individuals with that disease. Therefore, the fact that technologies have arisen that can simultaneously detect several, possibly hundreds, of biomarkers has propelled the field towards the development of multianalyte-based in vitro diagnostic early detection tests for cancer using body fluids such as serum, plasma, sputum, saliva, or urine. These multianalyte tests may be based on the detection of serum autoantibodies to tumor antigens, the presence of cancer-related proteins in serum, or the presence of tumor-specific genomic changes that appear in plasma as free DNA. The implementation of non-invasive diagnostic approaches to detect early stage cancer may provide the physician with evidence of cancer, but the question arises as to how the information will affect the pathway of clinical intervention. The confirmation of a positive result from an in vitro diagnostic cancer test may involve relatively invasive procedures to establish a true cancer diagnosis. If in vitro diagnostic tests are proven to be both specific, i.e. rarely produce false positive results due to unrelated conditions, and sufficiently sensitive, i.e. rarely produce false negative results, then such screening tests offer the potential for early detection and personalized therapeutics using multiple disease-related targets with convenient and non-invasive means. Here we discuss the technical and regulatory barriers inherent in development of clinical multianalyte biomarker assays.

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 332 ◽  
Author(s):  
Petr G. Lokhov ◽  
Oxana P. Trifonova ◽  
Dmitry L. Maslov ◽  
Steven Lichtenberg ◽  
Elena E. Balashova

A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is designed, manufactured and used in the same laboratory (i.e., an in-house test). In this study, a metabolomics-based LDT was developed. This test involves a blood plasma preparation, direct-infusion mass spectrometry analysis with a high-resolution mass spectrometer, alignment and normalization of mass peaks using original algorithms, metabolite annotation by a biochemical context-driven algorithm, detection of overrepresented metabolic pathways and results in a visualization in the form of a pathway names cloud. The LDT was applied to detect early stage Parkinson’s disease (PD)—the diagnosis of which currently requires great effort due to the lack of available laboratory tests. In a case–control study (n = 56), the LDT revealed a statistically sound pattern in the PD-relevant pathways. Usage of the LDT for individuals confirmed its ability to reveal this pattern and thus diagnose PD at the early-stage (1–2.5 stages, according to Hoehn and Yahr scale). The detection of this pattern by LDT could diagnose PD with a specificity of 64%, sensitivity of 86% and an accuracy of 75%. Thus, this LDT can be used for further widespread testing.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2767
Author(s):  
Jiawei Li ◽  
Xin Guan ◽  
Zhimin Fan ◽  
Lai-Ming Ching ◽  
Yan Li ◽  
...  

Breast cancer is the most common cancer in women worldwide. Accurate early diagnosis of breast cancer is critical in the management of the disease. Although mammogram screening has been widely used for breast cancer screening, high false-positive and false-negative rates and radiation from mammography have always been a concern. Over the last 20 years, the emergence of “omics” strategies has resulted in significant advances in the search for non-invasive biomarkers for breast cancer diagnosis at an early stage. Circulating carcinoma antigens, circulating tumor cells, circulating cell-free tumor nucleic acids (DNA or RNA), circulating microRNAs, and circulating extracellular vesicles in the peripheral blood, nipple aspirate fluid, sweat, urine, and tears, as well as volatile organic compounds in the breath, have emerged as potential non-invasive diagnostic biomarkers to supplement current clinical approaches to earlier detection of breast cancer. In this review, we summarize the current progress of research in these areas.


2000 ◽  
Vol 55 (7-8) ◽  
pp. 649-656 ◽  
Author(s):  
Reneta A. Toshkova ◽  
Petia A. Dimitrova ◽  
Emilia H. Ivanova ◽  
Pavlina A. Dolashka ◽  
Maria B. Angelova ◽  
...  

Abstract Investigation on the immunoprotective activity of Cu/Zn superoxide dismutase from Humicola lutea 103 AL (HLSOD) in hamsters with transplanted myeloid tumor was performed. Survivability, tumor growth and tumor transplantability were followed. The immune status of tumor-bearing animals, injected with the optimal protective HLSOD dose, was examined during 27 days after tumor transplantation by the following parameters: (i) the number, migration and phagocytic activity of peritoneal macrophages, (ii) the phagocytic activity of blood polymorphonuclear leukocytes (PMNs), (iii) the responsibility in vitro of spleen lymphocytes to T and B cell mitogens. It was established that intraperitoneal inoculation of HLSOD produced a protective effect on the development of tumors. Elongation of the latent time for tumor appearance and inhibition of the tumor growth were observed. The decreased percentage of mortality in early stage of tumor progression was established. Immunological studies on tumor-bearing hamsters (TBH) induced a tem porary immunorestoring effect on the suppressed phagocytic activities of peritoneal macrophages and blood PMNs during the first 14 days of tumor development. Moreover, HLSOD showed an expressed stimulating effect on proliferative activity in vitro of spleen B lymphocytes from healthy and TBH as well. The immunorestoring and protective effect of the enzyme was probably due to improve of the oxidant-antioxidant balance in peritoneal phagocytes. The tem porary character of the effect can be explained with the interference of immunosuppressing factors produced by tumor tissue as well as by the presence of tumor antigens, tumor cells and antigen-antibody complexes in the circulation.


Author(s):  
G J Verkerke ◽  
H Schraffordt Koops ◽  
R P H Veth ◽  
J Oldhoff ◽  
H K L Nielsen ◽  
...  

A malignant tumour may develop around the knee joint of a child. In the majority of cases it will then be necessary to resect the involved bone with adjacent tissue. A joint team of Groningen University Hospital and University of Twente is currently working on the project of developing a modular endoprosthetic system to bridge the defect resulting from the resection. Since the other, normal, leg continues to grow, the endoprosthetic system will have to include an element the length of which can be adjusted non-invasively. The main conditions to be met by the lengthening element are non-invasive continuous adjustability and a maximum total lengthening of 114 mm. This was achieved by using an external magnetic field. Animal experiments showed that the lengthening element worked well, although moisture infiltrated the telescopic tubes and the lengthening element was covered by proliferating bone at an early stage. Also, the necessary magnetic field proved to be larger than calculated. In a revised design, these problems are resolved. In vitro tests show that the new lengthening element meets all requirements.


2017 ◽  
Vol 20 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Elena Sergeevna Kamyshova ◽  
Irina Nikolaevna Bobkova ◽  
Irina Mikhailovna Kutyrina

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus associated with the progressive deterioration of renal function. Although microalbuminuria is considered as a gold standard for DN diagnosis, it has limited predictive powers and specificity as a diagnostic tool for the early stage of DN. Therefore, new biomarkers are required for the early detection of DN. Studies using in vitro and in vivo models of DN have revealed an important role of microRNAs (miRNAs), short non-coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression, in DN development. Recent studies have shown that the dysregulation of miRNAs, which is associated with the key features of DN, such as the mesangial expansion and accumulation of extracellular matrix proteins, is related to fibrosis and glomerular dysfunction. Thus, the up- and downregulation of miRNA expression in the renal tissue or biological fluids, including urine, may represent new biomarkers for the diagnosis and monitoring of DN progression. In this review, we highlight the significance of miRNAs as biomarkers for the early detection of DN and emphasise their potential role as a therapeutic target.


1974 ◽  
Vol 60 (3) ◽  
pp. 203-210 ◽  
Author(s):  
Sergio Tognella ◽  
Giovanni Mantovani ◽  
Carlo Floris ◽  
Letizia Cengiarotti ◽  
Gennaro S. Del Giacco ◽  
...  

The macrophage electrophoretic migration test (MEM test) of Field and Caspary was used to study the sensitization to tumor antigens of blood lymphocytes of patients with solid tumor (7), chronic lymphatic leukemia (3), and Hodgkin's disease (8). Our preliminary results are partially in keeping with those of the English authors: blood lymphocytes from some patients with malignant neoplasm seem to be sensitised to crude cancer material irrespective of the type of the tumor from which it derives. The MEM test was negative in the 4 patients with Hodgkin's disease in remission and positive in the 4 patients with active disease. It is believed that further studies are needed before accepting this test as an in vitro diagnostic test for cancer.


2020 ◽  
Vol 14 (4) ◽  
pp. 7600-7608
Author(s):  
W. A. A Saad ◽  
Mohd Azuwan Mat Dzahir ◽  
Yamamoto Shinichirou ◽  
Mohamed Hussein ◽  
Maziah Mohamad ◽  
...  

The change of the spinal curvature in completing a variety of daily tasks is essential to independent living. There is still a lack of studies highlighting the lumbar segmental contribution during sit-to-stand (STS) and stand-to-flexion (STF) using non-invasive study. The purpose of this study is to compare the spine kinematics by defining lumbar as a single and multi-segmental during continuous daily motion in healthy Asian adults using a non-invasive approach. During STS, most subjects implemented kyphotic lumbar curve during the early stage of motion which revealed poor posture implementation and significant differences in the lumbar kinematics which were only noticeable at specific phases between both approaches. A significant difference in multi-segmental behaviour was observed only at the end of the motion. All three segments displayed different time responses during the transition from kyphotic to lordotic curve. Passive/delayed behavior within the lower lumbar segment was observed between 0-50% of motion completion. During STF, statistically significant differences were found between assuming lumbar as a single and multi-segment in all phases. This in vitro study identified characteristic motion patterns in the lumbar spine during daily motions. The results provided a clear description of the healthy spinal condition of adults and may serve to identify specific multi-segmental contribution.


2013 ◽  
Vol 9 (1) ◽  
Author(s):  
Henning Hanken ◽  
Juliane Kraatz ◽  
Ralf Smeets ◽  
Max Heiland ◽  
Marco Blessmann ◽  
...  

Abstract Objective The disease specific five-year survival rate especially for patients with advanced oral cancer has not improved significantly over the period of time. The most effective way of combating this dilemma is an early detection, diagnosis and eradication of early-stage lesions and their precursors. The use of VELscope® using an autofluorescence as a diagnostic tool might be useful in early detection of oral malignant lesions. Materials and methods 120 patients with suspicious oral premalignant lesions were examined with two examination methods. They were randomly divided into two groups. Group 1 was examined conventional with white-light and group 2 was examined additionally to the white-light-examination with an autofluorescence visualization device, VELscope®. Biopsies were obtained from all suspicious areas identified in both examination groups (n = 52). The diagnostic strategies were compared regarding sensitivity and specificity. Results Based upon the result, use of the VELscope® leads to a higher sensitivity (22.0%), but regarding specificity the additional use of the VELscope® is inferior (8.4%). Conclusion The VELscope device is a simple, non-invasive test of the oral mucosa, which can help the experienced clinician to find oral precursor malignant lesions.


2017 ◽  
Vol 8 ◽  
pp. 1178122X1774478 ◽  
Author(s):  
Camila Freze Baez ◽  
Rafael Brandão Varella ◽  
Sonia Villani ◽  
Serena Delbue

About 40 years ago, the large and small tumor antigens (LT-Ag and sT-Ag) of the polyomavirus (PyVs) simian vacuolating virus 40 have been identified and characterized. To date, it is well known that all the discovered human PyVs (HPyVs) encode these 2 multifunctional and tumorigenic proteins, expressed at viral replication early stage. The 2 T-Ags are able to transform cells both in vitro and in vivo and seem to play a distinct role in the pathogenesis of some tumors in humans. In addition, they are involved in viral DNA replication, transcription, and virion assembly. This short review focuses on the structural and functional features of the HPyVs’ LT-Ag and sT-Ag, with special attention to their transforming properties.


2021 ◽  
Author(s):  
Miriam Sanso ◽  
Cristina Saura ◽  
Carolina Ortiz ◽  
Enrique Arenas Lahuerta ◽  
Judit Matito ◽  
...  

Abstract Pregnancy associated breast cancer (PABC) is an overall poor prognosis group compared to non-PABC breast cancer (BC), mainly due to late diagnosis. Effective screening approaches for early detection may improve its outcome. For the first time, we demonstrate the presence of cell-free tumor DNA (ctDNA) in the breast milk serum (sBM) of PABC in patients with early-stage disease and its ability to recapitulate somatic mutations present in the primary tumor. Moreover, our results demonstrate that sBM robustly surpasses plasma for tumor genetic profiling due to a prevalent shedding of ctDNA into the sBM in localized disease, as well as increased total cell-free DNA (cfDNA) abundance and integrity. Thus, we propose sBM as a potential new non-invasive liquid biopsy for a prompt detection of PABC.


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