Post-Translational Modifications of Thymidine Kinase 1

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Dr. Kim O’Neill, Microbiology and Molecular Biology

Thymidine kinase 1 (TK1) is one diagnostic and prognostic marker which has shown promising potential in a variety of solid tumors and hematological malignancies. Unfortunately there have been challenges associated with developing a clinically useful immunoassay which have prevented TK1 from being fully utilized in the clinical setting at present. One of the major goals of this study was to produce a dependable, reproducible, immunoassay to detect TK1 in serum from cancer patients. There have been many attempts at detecting protein or genetic material in the serum or sputum of lung cancer patients but these all have failed due to the lack of sensitivity in detecting minute amounts of material in early stage patients. In this study we propose a novel early detection test which may overcome many of these limitations. We demonstrate that this early detection enzyme-linked immune sorbent assay (ELISA) for thymidine kinase 1 (TK1) is highly sensitive and specific for the diagnosis of stage 1, node-negative lung cancer as well as more advanced lung cancer patients.

TK1 is a well-established cancer biomarker which is elevated in the serum and tumor tissue of many hematological and solid tumors including lung cancer 4-6. TK1 is efficacious as both a diagnostic and prognostic tool since changes in serum TK1 levels reflect a patient’s response to treatment and risk for recurrence 7-9. TK1 is elevated in the very early stages of malignancy. In fact, in a health screen of 8,135 individuals, 1.1% of individuals had elevated TK1 levels in which nearly 90% of those with elevated TK1 had pre-cancerous diseases 10. Included in those non-cancerous individuals with elevated TK1 was one individual who developed liver carcinoma 13 months following the reported high TK1 level. Several other studies have confirmed that TK1 is elevated in premalignancy. Guan et al. demonstrated that TK1 is significantly elevated in atypical ductal hyperplasia (ADH), ductal carcinoma in situ, and invasive ductal carcinoma compared to normal breast tissue 11, 12. However, they reported that TK1 was not significantly elevated in usual ductal hyperplasia tissue (UDH). Since TK1 was elevated in some pre-cancerous diseases such as ADH but not others, UDH, this indicated that perhaps elevated TK1 is associated with pre-cancerous diseases which have an increased risk of progression. This appears to be the case and has been confirmed in several large health screens including one with 35,365 individuals and one with 11,880 individuals 13, 14. In these health screens, individuals with pre-malignant diseases were found in both the elevated TK1 and normal TK1 groups although a significantly higher percentage of individuals with pre-malignant diseases had elevated TK1. The pre-malignant patients with elevated TK1 were more likely to show disease progression within 5 to 72 months compared to pre-malignant patients with normal TK1 (8.8% vs 0.2%) 14. Therefore, non-cancerous individuals with elevated TK1 levels had 3-5 fold increased risk of developing malignancies 14.

Lung cancer is frequently diagnosed in its advanced stages, and TK1 is elevated in lung cancer and other malignancies very early. Therefore, we sought to develop a TK1 ELISA to help identify lung cancer patients much earlier. The successful development of this assay will likely complement the use of CT scans to further identify groups of higher risk patients that may then obtain the necessary imaging. In this study, we demonstrate a sensitive and specific TK1 ELISA in which patients with operable lung cancer have significantly elevated serum TK1 levels compared to healthy individuals. Furthermore, we demonstrate that this TK1 ELISA is more sensitive than traditional methods of detecting TK1 in lung cancer patients.

This study introduces a novel TK1 ELISA which is both sensitive and specific. In addition to detecting significant differences in TK1 between advanced lung cancer and healthy individuals, there is a significant difference in TK1 levels of stage 1, nodenegative lung cancer patients and those of healthy individuals. TK1 concentrations, as detected by the TK1 ELISA, show significant differences between TK1 in lung cancer and healthy individuals while TK1 activity does not. This indicates that our novel TK1 ELISA is more sensitive and accurate than the traditional TK1 radioassay. This confirms other studies which have reported that in lung, breast, gastric, rectal, colorectal, brain cancer, leukemia, lymphoma, and hepatoma, TK1 protein concentration is more sensitive than TK1 activity 5.

In ROC analysis, the sensitivity is analogous to the true positive results or in other words, a lung cancer patient has TK1 levels above the cut-off value, as expected. A sensitivity of 100% would indicate that even asymptomatic lung cancer patients in the earliest stages of the disease, would have TK1 elevated above the cut-off value. On the other hand, specificity is analogous to true negative results. A specificity of 100% would have no false positives, such that every individual with TK1 above the cut-off value would have lung cancer. The two ROC curves representing either all lung cancer cases or only stage1, node-negative individuals had sensitivities and specificities of 81.8, 83.3 and 75.0, 83.3, respectively. A sensitivity or specificity between 90-99% could not be used for our data set since very few patients had concentrations above these cut-off values. In subsequent follow-up studies with larger sample sizes and more advanced tumors, it will likely be possible to have a sensitivity or specificity >90%. However, the AUC, sensitivity and specificity of the TK1 ELISA is comparable to other TK1 immunoassays which indicates this novel TK1 ELISA may be a reliable method of detection 14, 16, 18.

Furthermore, the positive predictive value represents the probability of lung cancer in individuals with a TK1 level above the cut-off value. On the other hand, the negative predictive value represents the probability that an individual with a TK1 level below the cut-off value does not have cancer. The positive and negative predictive values of either all lung cancer cases or only the earliest lung cancer stages were 90.3, 71.4 and 80.0, 79.0, respectively. Several studies have indicated that elevated TK1 is associated with risk for disease progression 10, 11, 13, 14, 19. Some tumors have a lower risk of progression and a corresponding low TK1 level 20. This is one possible explanation for why some individuals in our study with lung cancer had lower TK1 levels. This would contribute to a lower negative predictive value. A long-term follow-up study of lung cancer individuals with low preoperative TK1 levels would be needed to determine if their baseline serum TK1 levels could predict which individuals have an increased risk for disease progression. Although this study has not been conducted, similar studies have indicated that tumor TK1 expression and tumor TK1 activity can predict which tumors have an increased risk for recurrence 20-22.

Overall, it is clear that this novel TK1 ELISA is both sensitive and specific for the early detection of lung cancer. Further studies are needed to validate these exciting preliminary results. We believe this ELISA will aid in the early detection of lung cancer, the early detection of recurrent lung tumors, and monitoring a patient’s response to treatment. TK1 as detected by the traditional radioassay has already proved efficacious in these areas. Therefore, we believe that this novel TK1 ELISA will similarly prove effective in monitoring a patient’s response to treatment.

As a result of MEG funding these results have been accepted for publication.

During the course of this research the following papers and presentations were supported by funding from this MEG.

Presentations given by O’Neill lab 2012-2013 Sponsored by MEG funding

(Undergraduates are in bold graduates and post docs in italics)

  • 2012 Presented a poster at the Undergraduate Caucus of the Annual Meeting of the American Association for Cancer Research in Chicago April 2012, entitled,’ S2AMN: A potential non-toxic anti-cancer therapy. A. M. El- Naggar1,2, A. M. Chavez1, E. C. Peterson1, R.Kuttab1, R. A. Robison1 and K. L. O’Neill1
  • 2012 Presented a poster at the Undergraduate Caucus of the American Association for Cancer Research in Chicago April 2012, entitled, ‘Blueberries: Conventional Cancer Prevention. Ryan D. Kraus, Andreas Martinez, Kylie Measom, Matt Gill, Gupta Gaytri, Andrew Garrett, Richard Robison, and Kim L. O’Neill.
  • 2012 Presented a poster at the Undergraduate Caucus of the American Association for Cancer Research in Chicago April 2012, entitled, ‘How ‘Bout them Apples? Kylie Measom, Andrés D. Martinez, Erin M. Sharp, Timothy C. Michaelis, Kim L. O’Neill.
  • 2012 Presented a poster at the Undergraduate Caucus of the American Association for Cancer Research in Chicago April 2012, entitled, ‘Fortunella margarita: The little gold gem of the citrus family. James N. McCoy, Adam J. Grooms, Joshua Emerson, Ryan D. Kraus, Andres Martinez, Atif Elnaggar, Kim L. O’Neill.
  • 2012 Presented a poster at the Undergraduate Caucus of the American Association for Cancer Research in Chicago April 2012, entitled, ‘Differences in Intracellular Antioxidant Levels between Healthy and Cancerous Lymphocytes Adam J. Grooms, James N. McCoy, Atif Elnaggar, Michael Q. Sanderson, Andrew R. Garrett, and Kim L. O’Neill.
  • 2012 Presented a poster at the Undergraduate Caucus of the American Association for Cancer Research in Chicago April 2012, entitled, ‘Setting the Clock: Tumor TK1 is a Prognostic Marker for Disease Recurrence. M. Alegre1, B. Germann1, M. Leavitt2, D. Eggett3, N. Killpack2, S. Burton1, A. Orton2, C. Leavitt2 and K. L. O’Neill1
  • 2012 Presented poster at the Annual meeting of the American Association for Cancer Research in Chicago April 2012, entitled,’ S2AMN: A potential nontoxic anti- cancer therapy. A. M. El-Naggar1,2, A. M. Chavez1, E. C. Peterson1, R.Kuttab1, R. A. Robison1 and K. L. O’Neill1
  • 2012 Presented poster at the Annual meeting of the American Association for Cancer Research in Chicago April 2012, entitled, ‘Blueberries: Conventional Cancer Prevention. Ryan D. Kraus, Andreas Martinez, Kylie Measom, Matt Gill, Gupta Gaytri, Andrew Garrett, Richard Robison, and Kim L. O’Neill.
  • 2012 Presented poster at the Annual meeting of the American Association for Cancer Research in Chicago April 2012, entitled, ‘How ‘Bout them Apples? Kylie Measom, Andrés D. Martinez, Erin M. Sharp, Timothy C. Michaelis, Kim L. O’Neill.
  • 2012 Presented poster at the Annual meeting of the American Association for Cancer Research in Chicago April 2012, entitled, ‘Setting the Clock: Tumor TK1 is a Prognostic Marker for Disease Recurrence. M. Alegre1, B. Germann1, M. Leavitt2, D. Eggett3, N. Killpack2, S. Burton1, A. Orton2, C. Leavitt2 and K. L. O’Neill1
  • 2012 Presented poster at the Keystone Symposia on Molecular and Cellular Biology meeting entitled The Role of Inflammation during Carcinogenesis, Dublin Ireland May 20-25, 2012 entitled, ‘A Tumor Microenvironment Rich in Macrophages could be Aiding Metastasis’ K.L. O’Neill, A Clement, A. El-Naggar and R. Robison.
  • 2012 Drake, D., C. Grandela, K.L. O’Neill, and R.A. Robison. Comparative analysis of established DNA quantification methods. Intermountain Branch of the American Society for Microbiology Annual Meeting. Oral Session 1, Abstract #3, p.4, April 7, 2012. Pocatello, ID.
  • 2012 Lowe, C-W., B.A. Satterfield, J.K. March, A.B. Bunnell, K.L. O’Neill, and R.A. Robison. Quantitative real-time multiplex PCR assay for rapid detection and discrimination of Burkholderia pseudomallei and Burkholderia thailandensis. Intermountain Branch of the American Society for Microbiology Annual Meeting. Oral Session 2, Abstract #6, p.7, April 7, 2012. Pocatello, ID.
  • 2012 March, J.K., M.D. Pratt, G.B. Schaalje, C-W. Lowe, A.B. Bunnell, K.L. O’Neill, and R.A. Robison. The susceptibility of Bacillus subtilis, Clostridium sporogenes, and virulent Bacillus anthracis spores to peracetic acid- and glutaraldehyde-based disinfectants. Intermountain Branch of the American Society for Microbiology Annual Meeting. Oral Session 2, Abstract #7, p.7, April 7, 2012. Pocatello, ID.
  • 2012 March, J.K., M.D. Pratt, G. B. Schaalje, CW Lowe, A.B. Bunnell, K.L. O’Neill, and R.A. Robison. Differential effects of heat-shocking Bacillus subtilis, Clostridium sporogenes, and virulent Bacillus anthracis spores following disinfectant treatment. General Meeting of the American Society for Microbiology, Session 114/Q, Abstract # 1510, p. 160. June 18, 2012. San Francisco, CA.
  • 2012 Lowe, C-W, B.A. Satterfield, J.K. March, A.B. Bunnell, K.L. O’Neill, and R.A. Robison. A real-time multiplex PCR assay for rapid identification and differentiation of Burkholderia pseudomallei and Burkholderia thailandensis. General Meeting of the American Society for Microbiology, Session 126/C, Abstract # 1721, p. 170. June 18, 2012. San Francisco, CA.
  • 2012 Presented poster at the 41st Annual Meeting of the Autumn Immunology Conference, entitled, ‘Caffeine affects Macrophage Engulfment’. Steck, R., E. Weagel, M. Gustafsson, P. Liu, A. Elnaggar, and K.L. O’Neill. November 16- 19, Chicago, Illinois.
  • 2013 Presented talk at the Annual American Society for Microbiology Branch Meeting Idaho State University, March 9th 2013, entitled, ‘Macrophages may be polarized by apoptotic and necrotic cancer cells..’ Livingston, J. Lee.E.J. Barlow, S. El-Naggar, A.M. , Liu, P. Robison, R. A. and O’Neill K.L.
  • 2012 Presented talk at the 41st Annual Meeting of the Autumn Immunology Conference, entitled, ‘Caffeine affects Macrophage Engulfment’. E. Weagel, R. Steck, M. Gustafsson, P. Liu, A. Elnaggar, and K.L. O’Neill. November 16-19, Chicago, Illinois.
  • 2013 Presented talk at the intermountain Branch meeting of the American Society for Microbiology at Idaho State University, Pocatello, Idaho, March 9TH 2013 entitled,’ Macrophages may be polarized by apoptotic and necrotic cancer cells. Livingston, J., Lee E. J., Barlow, S., El-Naggar, A. M., Weagel, E., Liu, P., Robison R., O’Neill, K. L.(This presentation (by one of my undergraduates) won first prize in the graduate competition.
  • 2013 Presented poster at the 8th Annual Undergraduate Student Caucus and Poster Competition at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘The Potential of Resveratrol and Nagami Kumquat extracts in facilitating DNA repair in Raji cells’. Albert V. Helsing1, Atif Elnaggar1, 2, Philip Lynch3, Michael Xiao1, Madison Ramsden1, B. Fabrizio Alegre1, Evita Weagel1, James N. McCoy1, Richard A. Robison1, and Kim L. O’Neill.
  • 2013 Presented poster at the 8th Annual Undergraduate Student Caucus and Poster Competition at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘Cytototoxicity and mode of action of two lichen extracts, Tuckermannopsis ciliaris and Xanthoparmelia chlorochroa against Burkitt’s Lymphoma (Raji) cell and Human colon cancer cell line (HT-29)’ Shrestha, G.1,2, El-Naggar, A. M.3,4, Boswell, M. R.3, Derenthal, S. C.3, Weagel, E.3, St. Clair, L. L.1,2, Robison, R.3, and O’Neill, K. L.3
  • 2013 Presented poster at the 8th Annual Undergraduate Student Caucus and Poster Competition at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘Thymidine kinase 1 as a possible therapeutic target in Burkitt’s lymphoma’ C. A. Hamilton, J. J. Bell, S. R. Burton, C. R. Madsen, M. K. Ramsden, S. C. Derenthal, P. Liu, R. Robison, & K.L. O’Neill.
  • 2013 Presented poster at the 8th Annual Undergraduate Student Caucus and Poster Competition at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘Apoptotic and Necrotic Signals may Modulate Macrophage Polarization’. E. J. Lee1, S. Barlow1, A.M. El-Naggar,1, 2 E. Weagel1, P.G. Liu1, 3, J. Livingston1, R. Robison1, and K.L O’Neill1
  • 2013 Presented poster at the 8th Annual Undergraduate Student Caucus and Poster Competition at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘Mutagenic effects of inorganic particulate matter on Raji and HepG2 cell lines exposed to ultraviolet radiation’. Michael Xiao1, 2, Atif El-Naggar1, 3, Albert V. Helsing1, Philip M. Lynch4, Melissa M. Alegre1, Richard A. Robison1, and Kim L. O’Neill1
  • 2013 Presented poster at the 8th Annual Undergraduate Student Caucus and Poster Competition at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘Differences in cellular antioxidant activity in Burkitt’s lymphoma and normal human lymphocytes’. Evita G. Weagel1, Andres Martinez1, Atif ElNaggar1, Sean Ellis1, Ping Guo Liu2, Richard A. Robison1, and Kim L. O’Neill1.
  • 2013 Presented poster at the 8th Annual Undergraduate Student Caucus and Poster Competition at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘A qPCR and Engulfment Study of Cytokine Expression with Macrophages and Tumors’. Lucas Aidukaitis, Evita Weagel, Richard Robison, and Kim L. O’Neill.
  • 2013 Presented poster at the 8th Annual Undergraduate Student Caucus and Poster Competition at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘The effect of caffeine on DNA repair’. M Ramsden, A Helsing, M Xiao, J Holloway, R Robison, and K L O’Neill.
  • 2013 Presented poster at the 8th Annual Undergraduate Student Caucus and Poster Competition at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘Phagocytic regulation through exogenous caffeine exposure in whole-blood macrophages. Ryan Steck, Matthew Wells, PingGuo Lui, Atif Elnaggar, and Kim L. O’Neill.
  • 2013 Presented poster at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘The Potential of Resveratrol and Nagami Kumquat extracts in facilitating DNA repair in Raji cells’. Albert V. Helsing1, Atif Elnaggar1, 2, Philip Lynch3, Michael Xiao1, Madison Ramsden1, B. Fabrizio Alegre1, Evita Weagel1, James N. McCoy1, Richard A. Robison1, and Kim L. O’Neill.
  • 2013 Presented poster at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘Cytototoxicity and mode of action of two lichen extracts, Tuckermannopsis ciliaris and Xanthoparmelia chlorochroa against Burkitt’s Lymphoma (Raji) cell and Human colon cancer cell line (HT-29)’ Shrestha, G.1,2, El-Naggar, A. M.3,4, Boswell, M. R.3, Derenthal, S. C.3, Weagel, E.3, St. Clair, L. L.1,2, Robison, R.3, and O’Neill, K. L.3
  • 2013 Presented poster at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘Mutagenic effects of inorganic particulate matter on Raji and HepG2 cell lines exposed to ultraviolet radiation’. Michael Xiao1, 2, Atif El-Naggar1, 3, Albert V. Helsing1, Philip M. Lynch4, Melissa M. Alegre1, Richard A. Robison1, and Kim L. O’Neill1
  • 2013 Presented poster at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘Differences in cellular antioxidant activity in Burkitt’s lymphoma and normal human lymphocytes’. Evita G. Weagel1, Andres Martinez1, Atif ElNaggar1, Sean Ellis1, Ping Guo Liu2, Richard A. Robison1, and Kim L. O’Neill1.
  • 2013 Presented poster at the Annual Meeting of The American Association for Cancer Research (AACR), Washington DC, April 5-10th 2013, entitled ‘Phagocytic regulation through exogenous caffeine exposure in whole-blood macrophages. Ryan Steck, Matthew Wells, PingGuo Lui, Atif Elnaggar, and Kim L. O’Neill.
  • 2013 Presented poster at the Botany 2013 Conference July 27-31 2013 in New Orleans. Entitled, ‘Can we cure cancer with lichens?’ Shrestha, Gajendra, Leavitt, Steven D., St Clair, Larry, O’Neill, Kim L.
  • 2013 Presented poster at the 16th annual meeting of the American Society of Gene and Cell Therapy, May 15-18, 2013, Salt Lake City, UT “Investigating macrophage induction of metastasis: a precursor to identify therapeutic targets” Trevor Memmott, Evita Weagel, Justin Livingston, PingGuo Liu, Atif Elnaggar, Richard Robison, Kim O’Neill.

Papers published by O’Neill Lab 2012-2013 Sponsored by MEG Funding

  • 99. Gupta-Elera, Gaytri; Garrett, Andrew R.; Robison, Richard A.; O’Neill, Kim L. 2012 The role of oxidative stress in prostate cancer. European Journal of Cancer Prevention. 21(2):155-162, March 2012.
  • 100. Gaytri Gupta-Elera, Andrew Garrett, Andres Martinez, Ryan D. Kraus, Richard Robison and Kim O’Neill 2012. A Comparison of Antioxidant Properties in Organic and Conventional Blueberries. Journal of Food Research, Vol 1, #3 p1-7
  • 101. M. Alegre, R. Robison, and K.L. O’Neill 2012 Thymidine kinase 1 upregulation is an early event in breast tumor formation. Journal of Oncology, Vol 2012, Article ID 575647, 5 pages.
  • 102. Gunnell, M.K., C.D. Lovelace, B.A. Satterfield, E.A. Moore, K.L. O’Neill, and R.A. Robison. 2012. A multiplex real-time PCR assay for the detection and differentiation of Francisella tularensis subspecies. Journal of Medical Microbiology 61 (11):1525-1531.
  • 103. March, J.K., M.N. Cohen, J.M. Lindsey, D.A. Millar, C-W Lowe, A.J. Bunnell, K.L. O’Neill, G.B. Schaalje, and R.A. Robison. 2012. The differential susceptibility of spores from virulent and attenuated Bacillus anthracis strains to aldehyde- and hypochlorite-based disinfectants. MicrobiologyOpen 1-8, doi: 10.1002/mbo3.45.
  • 104. A.R. Garrett, G. Gupta-Elera, M.A. Keller, R.A. Robison, and K.L. O’Neill . 2013 Bioactive Foods in Aging: The Role in Cancer Prevention and Treatment. Chapter 3, P33-42, Bioactive Food as Dietary Interventions for the Aging Population. Academic Press, Elsevier Inc. ISBN: 978-0-12-397155-5
  • 105 M. M. Alegre, R.A.Robison, and K.L. O’Neill. 2013 Thymidine Kinase 1:A Universal Marker for Cancer. Cancer and Clinical Oncology; Vol. 2, No. 1 p159-167
  • 106. A.B Clifford, A. M. Elnaggar, R.A. Robison, and K.L. O’Neill 2013 Investigating the role of macrophages in tumor formation using a MaFIA mouse model. Oncology Reports Vol 30 (2) p890-896.

    • 107. C.W. Lowe, J.K. March, A.J. Bunnell, K.L. O’Neill, R.A. Robison 2013 PCRbased methodologies used to detect and differentiate the Burkholderia pseudomallei complex: B. pseudomallei, B. mallei, and B. thailandensis. Current Issues in Molecular Biology Vol 16 p23-54.

  • 108. MM Alegre, M.H. Knowles, R.A. Robison, K.L. O’Neill. 2013 The Mechanics behind Breast Cancer Prevention. Asian Pacific Journal of Cancer Prevention, Vol 14 (4)
  • 109 MM Alegre,, R.A. Robison, K.L. O’Neill. 2014 The Clinical significance and Biology of Thymidine Kinase 1. Oncology –Theory and Practice, iConcept Press Ltd. Australia.
  • 110. Andrew R Garrett, Evita G Weagel, Andres D Martinez, M Heaton, Richard A Robison, Kim L. O’Neill. 2014 A novel method for predicting antioxidant activity based on amino acid structure. (Accepted ) Journal of Food Chemistry
  • 111. Melissa M Alegre1, Michael J Weyant2, Daine T Bennett2, Jessica A Yu2, Madison K Ramsden1, Atif Elnaggar1,3, Richard A Robison1, Kim L O’Neill1. 2014 Serum Detection of Thymidine Kinase 1 as a Means of Early Detection of Lung Cancer Anticancer Research (Submitted).
  • 112. Michael Xiaoa, b, Albert V. Helsinga, Philip M. Lynchc, Atif El-Naggara, d, Melissa M. Alegrea, Richard A. Robisona, and Kim L. O’Neilla, * 2014 DNA damage caused by inorganic particulate matter on Raji and HepG2 cell lines exposed to ultraviolet radiation. Mutation Research (Submitted)
  • 113. Trevor Memmott, Evita Weagel, Chris Hamilton, Richard A. Robison and Kim L. O’Neill, 2014. Oxidative Stress Imbalance in the Development of Prostate Cancer Book Chapter 8 Free Radicals: The Role of Antioxidants and Pro-Oxidants in Cancer Development. Ed. William Stone, Nova Publications (In press)
  • 114. Chris Hamilton, Lucas Aidukaitis, Pinggou Liu, Richard Robison, and Kim L. O’Neill 2014. Dietary Antioxidants in Prostate Cancer. Cancer: Oxidative Stress and Dietary Antioxidants. Chapter 17 Ed. Preedy, Elsevier Publishing (In press)
  • 115. Gajendra Shrestha, Larry L St. Clair, and Kim O’Neill, 2014 The immunostimulating role of lichen compounds: A review. Phytomedicine, Elsevier Publishing (Submitted)
  • 116. Gajendra Shrestha,a, b Atif M. El-Naggar, c,d Larry L. St. Clair, a,b and Kim L. O’Neill 2014. Anticancer activities of selected species of North American lichen extracts. Phytotherapy Research. (Submitted)

Budget

All the budget was spend on supplies, labor, and travel to present data at conferences.

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