W Elaine Hardman

Marshall University, Хантингтон, West Virginia, United States

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Publications (81)311.24 Total impact

  • Cancer Research 08/2015; 75(15 Supplement):1678-1678. DOI:10.1158/1538-7445.AM2015-1678 · 9.33 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):5229-5229. DOI:10.1158/1538-7445.AM2015-5229 · 9.33 Impact Factor
  • Theodore R Witte · W Elaine Hardman ·
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    ABSTRACT: The consumption of omega-3 polyunsaturated fatty acids (n-3 PUFA) is associated with a reduced risk of breast cancer. Studies in animals and in vitro have demonstrated mechanisms that could explain this apparent effect, but clinical and epidemiological studies have returned conflicting results on the practical benefits of dietary n-3 PUFA for prevention of breast cancer. Effects are often only significant within a population when comparing the highest n-3 PUFA consumption group to the lowest n-3 group or highest n-6 group. The beneficial effects of n-3 PUFA eicosapentaenoic and docosahexaenoic on the risk of breast cancer are dose dependent and are negatively affected by total n-6 consumption. The majority of the world population, including the most highly developed regions, consumes insufficient n-3 PUFA to significantly reduce breast cancer risk. This review discusses the physiological and dietary context in which reduction of breast cancer risk may occur, some proposed mechanisms of action and meaningful recommendations for consumption of n-3 PUFA in the diet of developed regions.
    Lipids 04/2015; 50(5). DOI:10.1007/s11745-015-4011-2 · 1.85 Impact Factor
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    ABSTRACT: Colorectal cancer, unlike many other malignancies, may be preventable. Recent studies have demonstrated an inverse association between nut consumption and incidence of colon cancer; however, the underlying mechanisms are not fully understood. An emerging concept suggests that microribonucleic acids (miRNAs) may help explain the relationship between walnut consumption and decreased colorectal neoplasia risk. Seven days after HT-29 colon cancer cell injection, mice were randomized to either control or walnut diets for 25days of diet treatment. Thirty samples of tumor and of omental adipose were analyzed to determine changes in lipid composition in each dietary group. In the tumors of the walnut-containing diet, we found significant increases in α-linolenic, eicosapentaenoic, docosahexaenoic and total omega-3 acids, and a decrease in arachidonic acid, as compared to the control diet. Final tumor size measured at sacrifice was negatively associated with percentage of total omega-3 fatty acid composition (r=-0.641, P=.001). MicroRNA expression analysis of colorectal tumor tissue revealed decreased expression of miRNAs 1903, 467c and 3068 (P<.05) and increased expression of miRNA 297a* (P=.0059) in the walnut-treated group as compared to control diet. Our results indicate that changes in the miRNA expression profiles likely affect target gene transcripts involved in pathways of anti-inflammation, antivascularization, antiproliferation and apoptosis. We also demonstrate the incorporation of protective fatty acids into colonic epithelium of walnut-fed mice, which may independently alter miRNA expression profiles itself. Future studies of the mechanism of widespread miRNA regulation by walnut consumption are needed to offer potential prognostic and therapeutic targets. Copyright © 2015. Published by Elsevier Inc.
    The Journal of nutritional biochemistry 04/2015; 26(7). DOI:10.1016/j.jnutbio.2015.02.009 · 3.79 Impact Factor
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    Ivan L Cameron · Marko S Markov · W Elaine Hardman ·
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    ABSTRACT: This study provided additional data on the effects of a therapeutic electromagnetic field (EMF) device on growth and vascularization of murine 16/C mammary adenocarcinoma cells implanted in C3H/HeJ mice. The therapeutic EMF device generated a defined 120 Hz semi sine wave pulse signal of variable intensity. Murine 16/C mammary adenocarcinoma tumor fragments were implanted subcutaneously between the scapulae of syngeneic C3H mice. Once the tumor grew to 100 mm(3), daily EMF treatments were started by placing the cage of mice within the EMF field. Treatment ranged from 10 to 20 milli-Tesla (mT) and was given for 3 to 80 minutes either once or twice a day for 12 days. Tumors were measured and volumes calculated each 3-4 days. Therapeutic EMF treatment significantly suppressed tumor growth in all 7 EMF treated groups. Exposure to 20mT for 10 minutes twice a day was the most effective tumor growth suppressor. The effect of EMF treatment on extent of tumor vascularization, necrosis and viable area was determined after euthanasia. The EMF reduced the vascular (CD31 immunohistochemically positive) volume fraction and increased the necrotic volume of the tumor. Treatment with 15 mT for 10 min/d gave the maximum anti-angiogenic effect. Lack of a significant correlation between tumor CD 31 positive area and tumor growth rate indicates a mechanism for suppression of tumor growth in addition to suppression of tumor vascularization. It is proposed that EMF therapy aimed at suppression of tumor growth and vascularization may prove a safe alternative for patients whether they are or are not candidates for conventional cancer therapy.
    Cancer Cell International 12/2014; 14(1):125. DOI:10.1186/s12935-014-0125-5 · 2.77 Impact Factor

  • Biochemistry and Cell Biology 10/2014; 92(5):331-331. · 2.15 Impact Factor
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    ABSTRACT: Capsaicin, the pungent ingredient of chili peppers, displays potent anti-neoplastic activity in a wide array of human cancer cells. The present manuscript examines the signaling pathways underlying the apoptotic activity of capsaicin in human small cell lung cancer (SCLC) in vitro and in vivo. Studies in neuronal cells show that capsaicin exerts its biological activity via the transient receptor potential vanilloid (TRPV) superfamily of cation-channel receptors. The TRPV family is comprised of six members (TRPV1–6). Capsaicin is a known agonist of the TRPV1 receptor. We observed that capsaicin-induced apoptosis in human SCLC cells was mediated via the TRPV receptor family; however it was independent of TRPV1. Surprisingly, the apoptotic activity of capsaicin required the TRPV6 receptor. Depletion of TRPV6 receptor by siRNA methodology abolished the apoptotic activity of capsaicin in SCLC cells. Immunostaining and ELISA showed that TRPV6 receptor was robustly expressed on human SCLC tissues (from patients) and SCLC cell lines but almost absent in normal lung tissues. This correlates with our results that capsaicin induced very little apoptosis in normal lung epithelial cells. The pro-apoptotic activity of capsaicin was mediated by the intracellular calcium and calpain pathway. The treatment of human SCLC cells with capsaicin increased the activity of calpain 1 and 2 by threefold relative to untreated SCLC cells. Such calpain activation, in response to capsaicin, was downstream of the TRPV6 receptor. Taken together, our data provide insights into the mechanism underlying the apoptotic activity of capsaicin in human SCLCs.
    APOPTOSIS 08/2014; 19(8). DOI:10.1007/s10495-014-1007-y · 3.69 Impact Factor
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    W Elaine Hardman ·
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    ABSTRACT: Epidemiology studies indicate that diet or specific dietary components can reduce the risk for cancer, cardiovascular disease and diabetes. An underlying cause of these diseases is chronic inflammation. Dietary components that are beneficial against disease seem to have multiple mechanisms of action and many also have a common mechanism of reducing inflammation, often via the NFκB pathway. Thus, a plant based diet can contain many components that reduce inflammation and can reduce the risk for developing all three of these chronic diseases. We summarize dietary components that have been shown to reduce cancer risk and two studies that show that dietary walnut can reduce cancer growth and development. Part of the mechanism for the anticancer benefit of walnut was by suppressing the activation of NFκB. In this brief review, we focus on reduction of cancer risk by dietary components and the relationship to suppression of inflammation. However, it should be remembered that most dietary components have multiple beneficial mechanisms of action that can be additive and that suppression of chronic inflammation should reduce the risk for all three chronic diseases.
    Nutrition research and practice 06/2014; 8(3):233-240. DOI:10.4162/nrp.2014.8.3.233 · 1.44 Impact Factor

  • Experimental Biology Meeting; 04/2014
  • W Elaine Hardman ·
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    ABSTRACT: Cancer may not be completely the result of novel or inherited genetic mutations but may in fact be a largely preventable disease. Researchers have identified biochemicals, including n-3 (ω-3) fatty acids, tocopherols, β-sitosterol, and pedunculagin, that are found in walnuts and that have cancer-prevention properties. Mouse studies in which walnuts were added to the diet have shown the following compared with the control diet: 1) the walnut-containing diet inhibited the growth rate of human breast cancers implanted in nude mice by ∼80%; 2) the walnut-containing diet reduced the number of mammary gland tumors by ∼60% in a transgenic mouse model; 3) the reduction in mammary gland tumors was greater with whole walnuts than with a diet containing the same amount of n-3 fatty acids, supporting the idea that multiple components in walnuts additively or synergistically contribute to cancer suppression; and 4) walnuts slowed the growth of prostate, colon, and renal cancers by antiproliferative and antiangiogenic mechanisms. Cell studies have aided in the identification of the active components in walnuts and of their mechanisms of action. This review summarizes these studies and presents the notion that walnuts may be included as a cancer-preventive choice in a healthy diet.
    Journal of Nutrition 02/2014; 144(4). DOI:10.3945/jn.113.188466 · 3.88 Impact Factor
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    Flavia De Carlo · Theodore R Witte · W Elaine Hardman · Pier Paolo Claudio ·
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    ABSTRACT: Colorectal cancer is the third leading cause of cancer-related death in the western world. In vitro and in vivo experiments showed that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can attenuate the proliferation of cancer cells, including colon cancer, and increase the efficacy of various anticancer drugs. However, these studies address the effects of n-3 PUFAs on the bulk of the tumor cells and not on the undifferentiated colon cancer stem-like cells (CSLCs) that are responsible for tumor formation and maintenance. CSLCs have also been linked to the acquisition of chemotherapy resistance and to tumor relapse. Colon CSLCs have been immunophenotyped using several antibodies against cellular markers including CD133, CD44, EpCAM, and ALDH. Anti-CD133 has been used to isolate a population of colon cancer cells that retains stem cells properties (CSLCs) from both established cell lines and primary cell cultures. We demonstrated that the n-3 PUFA, eicosapentaenoic acid (EPA), was actively incorporated into the membrane lipids of COLO 320 DM cells. 25 uM EPA decreased the cell number of the overall population of cancer cells, but not of the CD133 (+) CSLCs. Also, we observed that EPA induced down-regulation of CD133 expression and up-regulation of colonic epithelium differentiation markers, Cytokeratin 20 (CK20) and Mucin 2 (MUC2). Finally, we demonstrated that EPA increased the sensitivity of COLO 320 DM cells (total population) to both standard-of-care chemotherapies (5-Fluorouracil and oxaliplatin), whereas EPA increased the sensitivity of the CD133 (+) CSLCs to only 5-Fluorouracil.
    PLoS ONE 07/2013; 8(7):e69760. DOI:10.1371/journal.pone.0069760 · 3.23 Impact Factor
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    ABSTRACT: It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those in the control diet mice. The final average tumor size in the walnut-diet animals was roughly one-fourth the average size of the prostate tumors in the mice that ate the control diet.
    Cancer Investigation 06/2013; 31(6). DOI:10.3109/07357907.2013.800095 · 2.22 Impact Factor
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    Johannes F Fahrmann · W Elaine Hardman ·
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    ABSTRACT: Background B-Cell chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States. Clinical treatment of CLL is often limited due to drug resistance and severe therapy-induced toxicities. We hypothesized that the omega 3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), would increase the sensitivity of malignant B-lymphocytes to anti-cancer drugs doxorubicin, vincristine and/or fludarabine in vitro and that increased sensitivity is achieved by alterations in cell-cycle progression leading to growth inhibition and/or enhanced cell death. We further postulate that enhanced sensitivity is dependent on the formation of lipid peroxides and to the generation of reactive oxygen species (ROS). Methods In the present study, B-CLL-derived leukemic cell lines EHEB and MEC-2 and the B-Prolymphocytic leukemic-derived (PLL) cell line JVM-2 were tested for in vitro sensitivity against doxorubicin, vincristine or fludarabine in the presence or absence of vehicle, arachidonic acid (omega 6), EPA or DHA. Cell cycle analysis and Annexin-V assays were performed to determine cell cycle progression and % apoptotic cells, respectively. Assays for malondialdehyde, a measure of lipid peroxidation, and DCF fluorescence assays, a measure of intracellular ROS, were performed to determine if enhanced sensitivity of cells to the drugs by n-3 was dependent on the formation of ROS. Results Our results indicated that: 1) EPA and DHA differentially sensitized B-leukemic cell lines EHEB, JVM-2 and MEC-2 to doxorubicin, vincristine and fludarabine in vitro; 2) n-3 alone and with drug treatment increased cell death and induced G2/M arrest in a cell-type specific manner; 3) lipid peroxidation increased in the presence of n-3; 4) there was higher lipid peroxidation in MEC-2 cells in presence of DHA and doxorubicin than with either alone; 5) n-3 increased generation of ROS in MEC-2, and 6) the addition of vitamin-E abrogated the increase in ROS generation and chemo-sensitivity of MEC-2 to doxorubicin by DHA. Conclusion N-3’s are promising chemo-sensitizing agents for the treatment of CLL. Selective enhancement of chemo-sensitivity of EHEB, JVM-2 and MEC-2 to drugs by n-3 that is not dependent on increased lipid peroxidation and ROS generation indicates alternative mechanisms by which n-3 enhances chemo-sensitivity.
    Lipids in Health and Disease 03/2013; 12(1):36. DOI:10.1186/1476-511X-12-36 · 2.22 Impact Factor
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    ABSTRACT: Recent case-controlled clinical studies show that bronchioalveolar carcinomas (BACs) are correlated with smoking. Nicotine, the addictive component of cigarettes, accelerates cell proliferation through nicotinic acetylcholine receptors (nAChRs). In this study, we show that human BACs produce acetylcholine (ACh) and contain several cholinergic factors including acetylcholinesterase (AChE), choline acetyltransferase (ChAT), choline transporter 1 (CHT1, SLC5A7), vesicular acetylcholine transporter (VAChT, SLC18A3) and nACh receptors (AChRs, CHRNAs). Nicotine increased the production of ACh in human BACs and ACh acts as a growth factor for these cells. Nicotine-induced ACh production was mediated by α7-, α3β2-, and β3-nAChRs, ChAT and VAChT pathways. We observed that nicotine upregulated ChAT and VAChT. Therefore, we conjectured that VAChT antagonists, such as vesamicol, may suppress the growth of human BACs. Vesamicol induced potent apoptosis of human BACs in cell culture and nude mice models. Vesamicol did not have any effect on EGF or IGF-II-induced growth of human BAC's. siRNA-mediated attenuation of VAChT reversed the apoptotic activity of vesamicol. We also observed that vesamicol inhibited Akt phosphorylation during cell death, and overexpression of constitutively active Akt reversed the apoptotic activity of vesamicol. Taken together, our results suggested that disruption of nicotine-induced cholinergic signaling by agents such as vesamicol may have applications in BAC therapy.
    Cancer Research 12/2012; 73(4). DOI:10.1158/0008-5472.CAN-12-3190 · 9.33 Impact Factor
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    ABSTRACT: Targeting the nuclear factor kappa B (NFκB) pathway is proposed as therapy for chronic lymphocytic leukemia (CLL). We hypothesized that an omega-3 fatty acids (n-3) supplement would suppress NFκB activation in lymphocytes of Rai Stage 0-1 CLL patients. The initial dose of 2.4 g n-3/day was gradually increased to 7.2 g n-3/day. After n-3 consumption: 1) plasma n-3 increased; 2) NFκB activation was suppressed in lymphocytes; 3) in vitro sensitivity of lymphocytes to doxorubicin was increased; and 4) expression of 32 genes in lymphocytes was significantly decreased.
    Cancer Investigation 11/2012; 31(1). DOI:10.3109/07357907.2012.743553 · 2.22 Impact Factor
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    Angiogenesis 03/2012; 15(2). DOI:10.1007/s10456-012-9258-0 · 4.88 Impact Factor
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    ABSTRACT: Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the α7-nicotinic acetylcholine receptor (α7-nAChR) on endothelial cells. Therefore, we conjectured that α7-nAChR antagonists may attenuate nicotine-induced angiogenesis and be useful for the treatment of human SCLC. For the first time, our study explores the anti-angiogenic activity of MG624, a small-molecule α7-nAChR antagonist, in several experimental models of angiogenesis. We observed that MG624 potently suppressed the proliferation of primary human microvascular endothelial cells of the lung (HMEC-Ls). Furthermore, MG624 displayed robust anti-angiogenic activity in the Matrigel, rat aortic ring and rat retinal explant assays. The anti-angiogenic activity of MG624 was assessed by two in vivo models, namely the chicken chorioallantoic membrane model and the nude mice model. In both of these experimental models, MG624 inhibited angiogenesis of human SCLC tumors. Most importantly, the administration of MG624 was not associated with any toxic side effects, lethargy or discomfort in the mice. The anti-angiogenic activity of MG624 was mediated via the suppression of nicotine-induced FGF2 levels in HMEC-Ls. MG624 decreased nicotine-induced early growth response gene 1 (Egr-1) levels in HMEC-Ls, and reduced the levels of Egr-1 on the FGF2 promoter. Consequently, this process decreased FGF2 levels and angiogenesis. Our findings suggest that the anti-angiogenic effects of MG624 could be useful in anti-angiogenic therapy of human SCLCs.
    Angiogenesis 12/2011; 15(1):99-114. DOI:10.1007/s10456-011-9246-9 · 4.88 Impact Factor
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    Juliana A Akinsete · Gabriela Ion · Theodore R Witte · W Elaine Hardman ·
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    ABSTRACT: Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to a high ω-3 diet containing canola oil and fish oil concentrate (FS). High ω-3 diet increased ω-3 and decreased ω-6 fat content of mice tissues. Average weights of prostate and genitourinary bloc were significantly lower in mice consuming high ω-3 diet at adulthood (CO-FS) than mice fed a lifetime high ω-6 diet (CO-CO). There was slower progression of tumorigenesis in dorsalateral prostate of CO-FS than in CO-CO mice. CO-FS mice had slightly lower plasma testosterone level at 24 and 40 weeks, significantly lower estradiol level at 40 weeks and significantly less expressed androgen receptor (AR) in the dorsalateral prostate at 40 weeks than CO-CO mice. Consumption of high ω-3 diet lowered the expression of genes expected to increase proliferation and decrease apoptosis in dorsalateral prostate. Our results suggest that consumption of high ω-3 diet slows down prostate tumorigenesis by lowering estradiol, testosterone and AR levels, promoting apoptosis and suppressing cell proliferation in C3(1)Tag mice.
    Carcinogenesis 10/2011; 33(1):140-8. DOI:10.1093/carcin/bgr238 · 5.33 Impact Factor
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    W Elaine Hardman · Gabriela Ion · Juliana A Akinsete · Theodore R Witte ·
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    ABSTRACT: Walnuts contain multiple ingredients that, individually, have been shown to slow cancer growth, including omega-3 fatty acids, antioxidants, and phytosterols. In previous research, consumption of walnuts has slowed the growth of implanted breast cancers. We wanted to determine whether regular walnut consumption might reduce the risk for developing cancer. Homozygous male C(3)1 TAg mice were bred with female SV129 mice consuming either the control AIN-76 diet or the walnut-containing diet. At weaning, the female hemizygous pups were randomized to control or walnut-containing diets and followed for tumor development. Compared to a diet without walnuts, consumption of walnuts significantly reduced tumor incidence (fraction of mice with at least one tumor), multiplicity (number of glands with tumor/mouse), and size. Gene expression analyses indicated that consumption of the walnut diet altered expression of multiple genes associated with proliferation and differentiation of mammary epithelial cells. A comparison with another dietary intervention indicated that the omega 3 content alone did not account for the extent of tumor suppression due to the walnut. The results of this study indicate that walnut consumption could contribute to a healthy diet to reduce risk for breast cancer.
    Nutrition and Cancer 08/2011; 63(6):960-70. DOI:10.1080/01635581.2011.589959 · 2.32 Impact Factor
  • Juliana A. Akinsete · W Elaine Hardman ·

    Cancer Research 07/2011; 71(8 Supplement):1816-1816. DOI:10.1158/1538-7445.AM2011-1816 · 9.33 Impact Factor

Publication Stats

1k Citations
311.24 Total Impact Points


  • 2011-2014
    • Marshall University
      • Department of Biochemistry and Microbiology
      Хантингтон, West Virginia, United States
  • 2013
    • The Huntington
      Сан Марино, California, United States
  • 1993-2008
    • University of Texas Health Science Center at San Antonio
      • • Department of Cellular and Structural Biology
      • • Department of Surgery
      San Antonio, TX, United States
  • 2002-2006
    • Pennington Biomedical Research Center
      Baton Rouge, Louisiana, United States
  • 1992-1999
    • University of Texas at San Antonio
      San Antonio, Texas, United States