Sensitivity and specificity of the empirical lymphocyte genome sensitivity (LGS) assay: implications for improving cancer diagnostics

Anderson, Diana; Najafzadeh, Mojgan; Gopalan, Rajendiran; Ghaderi, Nader; Scally, Andrew J.; Britland, Stephen; Jacobs, Badie K.; Reynolds, Paul D.; Davies, J D; Wright, Andrew; Al-Ghazal, Shariff; Sharpe, David; Denyer, M.

doi:10.1096/fj.14-254748

Cited by 25 publications

(24 citation statements)

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“…So by implication, this is an assay that evaluates generic, genomic, genotoxic processes and is thus an empirical assay of cancer susceptibility that does not require an understanding of the underlying causative mechanisms. 9 In the present study, results indicated that characterisation of differences in lymphocyte sensitivity to UV again enabled discrimination between cancer patients, pre/suspect cancer patients and healthy volunteers. However, since 2012 to facilitate the comet assay method, with UV treatment it was possible to standardise the procedure, and we modified the earlier LGS technique.…”

supporting

confidence: 50%

“…As pointed out by Anderson et al, 9 it remains an open question whether the increase in damage in cancer cells is a predictor of susceptibility or a consequence of disease. We know that therapeutics are not involved in this study since colorectal and prostate cancer, after treating with different UV intensity doses compared to healthy individuals, and suspected cancer patients (patients with polyposis coli and BPH) with different levels of responses to UV treatments.…”

Section: F I G U R E 5 Mean Log Of the Olive Tail Moment (Otms) (95% mentioning

confidence: 99%

“…The number of scored cells was 100 per dose. 9,10 There were some individuals with cancer and suspected cancer and healthy controls that did not follow the patterns in the damage of DNA in the other samples from the same groups Figure 6. These were samples which were difficult to distinguish the disease state by comparison with healthy controls.…”

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confidence: 99%

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Our previous case-control study observed isolated lymphocytes from 208 individuals and determined the differences in the sensitivity to genomic damage of lymphocytes derived from cancer patients, pre/suspect cancer patients and healthy volunteers using the Comet assay (Anderson et al, 2014). We adapted the LGS technique using a slightly different method and examined 700 more blood samples from 598 patients with cancer or suspected cancer and 102 healthy individuals.

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mentioning

confidence: 99%

“…[6][7][8] However up to the present time, finding an efficient practical method with a low cost and easy approach and use in laboratories over the world was not readily available. However, Anderson et al 2014 9 showed detecting genomic damage in lymphocytes from cancer and suspected cancer patient samples compared to healthy individuals using the Comet assay fulfilled this need. The entirety of the cancers tested exhibited responses that were worthy of comparison.…”

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Using a Modified Lymphocyte Genome Sensitivity (LGS) test or TumorScan test to detect cancer at an early stage in each individual

et al. 2018

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Our previous case‐control study observed isolated lymphocytes from 208 individuals and determined the differences in the sensitivity to genomic damage of lymphocytes derived from cancer patients, pre/suspect cancer patients and healthy volunteers using the Comet assay (Anderson et al, 2014). We adapted the LGS technique using a slightly different method and examined 700 more blood samples from 598 patients with cancer or suspected cancer and 102 healthy individuals. To help increase the sensitivity of the test and detect cancer at the level of each individual, we joined with the IMSTAR team who analysed our cells with their fully automated Pathfinder™ cell reader‐analyser system. With this reading and analysis system 4,000 to 10,000 cells were able to be read per slide. The new test which is called TumorScan is a highly sensitive test to detect any cancer at an early stage through the response of the white blood cells to UV treatment. These patient blood samples have also been collected at the stage before confirming diagnosis and treatment. There were four of these individuals with cancer who had received anti‐cancer treatment. The results from these patients showed a reverse pattern compared to non‐treated cancer patients and followed the pattern seen in healthy individuals. The results are consistent with the early results as reported in the above 2014 paper. Given the results from these samples were in a particularly challenging subgroup, whose cancer status was difficult to distinguish, the data suggest that the technique using the TumorScan system could exceed the area under the ROC curve >93% obtained in the earlier study on a group basis, whereas this present study was to detect cancer at an early stage in each individual.

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Section: F I G U R E 5 Mean Log Of the Olive Tail Moment (Otms) (95% mentioning

confidence: 99%

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confidence: 99%

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Using a Modified Lymphocyte Genome Sensitivity (LGS) test or TumorScan test to detect cancer at an early stage in each individual

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UV‐induced DNA damage response in blood cells for cancer detection

Farivar

Roberts

Ardakani³

et al. 2020

Med Devices & Sens

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Detection and diagnosis of cancer often require a combination of tests that are inconvenient and invasive for patients. There is therefore a need for new simple noninvasive tests able to detect cancer at various stages. Here, a novel photochemical assay for cancer detection in liquid biopsies is described. This proof of concept study shows that the response of peripheral blood mononuclear cells (PBMCs) to light-emitting diode (LED)-transmitted UV radiation can be used as an indicator of malignant disease. When exposed to UVB/C radiation, isolated PBMCs from prostate cancer patients presented with an acute dose-dependent DNA damage response that is distinct from that of PBMCs from healthy individuals. Importantly, this assay achieves sensitivity and specificity comparable to standard methods currently in clinical use. In summary, this work demonstrates that photochemical interrogation of PBMCs from cancer patients can be utilized for detection of malignant diseases. As such, the assay could potentially complement current gold standard cancer detection strategies for the benefit of patients and healthcare economy.

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ROS-induced oxidative damage in lymphocytes ex vivo/in vitro from healthy individuals and MGUS patients: protection by myricetin bulk and nanoforms

et al. 2020

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We investigated the protective role of myricetin bulk and nanoforms, against reactive oxygen species (ROS)-induced oxidative stress caused by hydrogen peroxide and tertiary-butyl hydro peroxide in lymphocytes in vitro from healthy individuals and those from pre-cancerous patients suffering with monoclonal gammopathy of undetermined significance (MGUS). The change in intracellular reactive oxygen species was measured once cells were treated with myricetin bulk forms and nanoforms with and without either hydrogen peroxide or tertiary-butyl hydro peroxide co-supplementation. The direct and indirect antioxidant activity of myricetin was spectrofluometrically measured using the fluorescent dye 2′,7′-dichlorofluorescin diacetate and using the Comet assay, respectively. Hydrogen peroxide (50 µM) and tertiary-butyl hydro peroxide (300 µM) induced a higher level of reactive oxygen species-related DNA damage and strand breaks. Addition of myricetin nanoform (20 µM) and bulk (10 µM) form could, however, significantly prevent hydrogen peroxide-and tertiary-butyl hydro peroxide-induced oxidative imbalances and the nanoform was more effective. Glutathione levels were also quantified using a non-fluorescent dye. Results suggest that myricetin treatment had no significant effect on the cellular antioxidant enzyme, glutathione. The current study also investigates the effect of myricetin on the induction of double-strand breaks by staining the gamma-H2AX foci immunocytochemically. It was observed that myricetin does not induce double-strand breaks at basal levels rather demonstrated a protective effect. Keywords Myricetin bulk forms and nanoforms • TBHP • hydrogen peroxide • Lymphocytes • MGUS patients • γ-H2AX

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Sensitivity and specificity of the empirical lymphocyte genome sensitivity (LGS) assay: implications for improving cancer diagnostics

Cited by 25 publications

References 44 publications

Using a Modified Lymphocyte Genome Sensitivity (LGS) test or TumorScan test to detect cancer at an early stage in each individual

Using a Modified Lymphocyte Genome Sensitivity (LGS) test or TumorScan test to detect cancer at an early stage in each individual

UV‐induced DNA damage response in blood cells for cancer detection

ROS-induced oxidative damage in lymphocytes ex vivo/in vitro from healthy individuals and MGUS patients: protection by myricetin bulk and nanoforms

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