Meghan L Lane

James A. Haley Veterans Hospital, Tampa, Florida, United States

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Publications (6)13.52 Total impact

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    ABSTRACT: Vessel dilator, a hormone synthesized in the heart, eliminates 71% of human small-cell lung cancers and 67% of human breast cancers growing in mice when given subcutaneously via osmotic pumps. The pharmacokinetic evaluation of subcutaneously administered vessel dilator has never been performed. Pharmacokinetics of A) administering vessel dilator by a subcutaneous bolus(ScB), B) via a 3-hour subcutaneous infusion (ScI) were compared with C) an intravenous(IV) bolus in male Fischer 344 rats. Half-life (t½) of vessel dilator via ScI was 54 minutes while IV and ScB t1/2 were 43 and 30 minutes. tmax for vessel dilator via IV, ScB, and ScI were 1.5, 23 and 156 minutes while Cmax for vessel dilator was 3749, 887 and 471 ng/L (normalized) for IV, ScB and ScI. Area under the curve (AUC0-∞) (ng h/mL) for vessel dilator was 1166, 880, and 1652 (normalized) for IV,ScB and ScI, respectively. The volume of distribution (L) for vessel dilator was 2.38, 0.92 and 1.08 for IV, ScB and SCI. Clearance was 1.69, 1.50 and 0.78 L/h for IV, ScB and SCI,. The plasma concentrations of vessel dilator after each of the 3 methods of treatment mirrored their predicted concentration-time profiles. We conclude that vessel dillator via ScI but as a significantly greater AUC, t½ and slowed clearance compared to IV or ScB (P < 0.001), suggesting it is the preferred method based upon pharmacokinetics to treat cancers.This article is protected by copyright. All rights reserved.
    Clinical and Experimental Pharmacology and Physiology 05/2014; · 2.41 Impact Factor
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    ABSTRACT: c-Fos is a cellular proto-oncogene which dimerizes with c-Jun proto-oncogene to form AP-1 transcription factor, which upregulates transcription of genes involved in proliferation and cancer formation. Four cardiac hormones, that is, long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide (KP) and atrial natriuretic peptide (ANP) with anticancer effects in vivo are potent inhibitors of the Ras-MEK 1/2-ERK 1/2 kinase cascade and signal transducer and activator of transcription-3 (STAT-3) that activate c-Fos and c-Jun. These four cardiac hormones were investigated for their effects on proto-oncogenes c-Fos and c-Jun within the nucleus of cancer cells. Four cardiac hormones were evaluated for their ability to decrease proto-oncogenes c-Fos and c-Jun, measured by ELISA in extracted nuclei of three human cancer cell lines. Vessel dilator, LANP, KP and ANP over a concentration range of 100 pM-10 μM, maximally decreased c-Fos by 61%, 60%, 61% and 59% in human hepatocellular cancer cells, by 82%, 74%, 78% and 74% in small-cell lung cancer cells, and by 82%, 73%, 78% and 74% in human renal adenocarcinoma cells. c-Jun was maximally reduced by vessel dilator, LANP, KP and ANP by 43%, 31%, 61% and 35% in hepatocellular cancer cells, by 65%, 49%, 59% and 40% in small-cell lung cancer cells, and by 47%, 43%, 57% and 49% in renal cancer cells. Four cardiac hormones are potent inhibitors of c-Fos and c-Jun proto-oncogenes within the nucleus of cancer cells.
    European Journal of Clinical Investigation 08/2013; · 3.37 Impact Factor
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    Meghan L Lane, David L Vesely
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    ABSTRACT: Circulating levels of leptin are increased in obesity and have been proposed to contribute to the development of hypertension in obese individuals. Four cardiac hormones, specifically, vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide and atrial natriuretic peptide (ANP), have blood pressure-lowering properties and correlate with the presence of hypertension in obesity. The objective of this study was to determine whether one or more of these cardiac hormones was able to decrease the levels of leptin in the hypothalamus, an area of the brain that has been demonstrated to synthesize more than 40% of leptin in the circulation. The effects of these four cardiac hormones on leptin were examined using dose-response curves in the rat hypothalamus, which synthesizes leptin. Vessel dilator, LANP, kaliuretic peptide and ANP maximally decreased the levels of leptin in hypothalamic cells by 79, 76, 80 and 62%, respectively (P<0.0001 for each). The cardiac hormones decreased leptin levels over a concentration range of 100 pM to 10 μM, with the most significant reductions in leptin levels occurring when the concentrations of the hormones were at micromolar levels. The results of the study suggest that the four cardiac hormones lead to significant reductions in hypothalamic leptin levels, which may be an important mechanism for alleviating leptin-induced hypertension in obesity.
    Experimental and therapeutic medicine 08/2013; 6(2):611-615. · 0.34 Impact Factor
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    ABSTRACT: Signal transducers and activators of transcription (STATs) are the final "switches" that activate gene expression patterns that lead to human malignancy. Extracellular signal-regulated kinases (ERK 1/2) activate STAT 3; four cardiovascular hormones inhibit ERK 1/2 kinases, leading to the hypothesis that they may also inhibit STATs. These four cardiac hormones, i.e., vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide (ANP), eliminate human cancers growing in mice. These four cardiac hormones' effects on STATs 1 and 3 were examined in human small-cell lung cancer and human pancreatic adenocarcinoma cells. Vessel dilator, LANP, kaliuretic peptide, and ANP maximally decreased STAT 3 by 88, 54, 55, and 65 %, respectively, at their 1 μM concentrations in human small-cell lung cancer cells and STAT 3 by 66, 57, 70, and 77 % in human pancreatic adenocarcinoma cells, respectively. The cardiac hormones (except LANP) also significantly decreased STAT 3 measured by Western blots. These cardiac hormones did not decrease STAT 1 in either human small-cell lung cancer or pancreatic adenocarcinoma cells. We conclude that these four cardiac hormones are significant inhibitors of STAT 3, but not STAT 1, in human small-cell lung cancer and pancreatic adenocarcinoma cells, which suggests a specificity for these hormones' anticancer mechanism(s) of action enzymology in human cancer cells.
    Molecular and Cellular Biochemistry 09/2012; · 2.33 Impact Factor
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    ABSTRACT: Eur J Clin Invest 2012; 42 (10): 1061-1067 ABSTRACT: Background  Vascular endothelial growth factor (VEGF) helps control tumour growth via causing new capillaries growth in tumours. Four cardiac hormones [i.e. vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide (KP) and atrial natriuretic peptide (ANP)] that eliminate up to up to 86% of human small-cell lung cancers growing in mice were investigated for their effects on VEGF and the VEGFR2/KDR/Flk-1 receptor. The VEGFR2 receptor is the main receptor mediating VEGF's cancer-enhancing effects. Materials and Methods  Four cardiac hormones were evaluated for their ability to decrease VEGF/VEGFR2 measured by ELISAs in three human cancer cell lines. Results  Vessel dilator, LANP, KP and ANP, over a concentration range of 100 pM to 10 μM, maximally decreased the VEGFR2 receptor in human pancreatic adenocarcinoma cells by 48%, 49%, 74% and 83%. Vessel dilator, LANP, KP and ANP decreased the VEGFR2 receptor by 77%, 89%, 88% and 67% in human small-cell lung cancer cells and by 48%, 92%, 64% and 71% in human prostate cancer cells. These results were confirmed with the cardiac hormones also decreasing the VEGFR2 receptor measured by Western blots. VEGF itself in pancreatic carcinoma cells was decreased by 42%, 58%, 36% and 40% by vessel dilator, LANP, KP and ANP. VEGF levels were decreased 25%, 23%, 17% and 23% in small-cell lung cancer cells and decreased by 24%, 20%, 23% and 24% in prostate cancer cells by vessel dilator, LANP, KP and ANP. Conclusion  Four cardiac hormones are the first dual inhibitors of VEGF and the VEGFR2/KDR/Flk-1 receptor.
    European Journal of Clinical Investigation 05/2012; 42(10):1061-7. · 3.37 Impact Factor
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    ABSTRACT: Four cardiac peptide hormones, namely vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide (ANP) have anticancer effects. The effects of these four cardiac hormones on human c-Jun-N-terminal kinase 2 (JNK2) were examined in human small cell lung cancer and human prostate cancer cells. Vessel dilator, LANP, kaliuretic peptide and ANP maximally reduced expression of JNK2 by 89%, 56%, 45%, and 28%, respectively (each at p<0.0001) in human small cell lung cancer cells. In human prostate adenocarcinoma cells, JNK2 was maximally decreased 76%, 56%, 45%, (each at p<0.0001), and 28% (p<0.01) secondary to vessel dilator, LANP, kaliuretic peptide and ANP, respectively. These results indicate that four cardiac hormones are significant inhibitors (by up to 89%) of JNK2 in human small cell lung cancer cells and up to 76% in human prostate adenocarcinoma cells as part of their anticancer mechanism(s) of action.
    Anticancer research 03/2012; 32(3):721-5. · 1.71 Impact Factor

Publication Stats

13 Citations
13.52 Total Impact Points

Institutions

  • 2012–2013
    • James A. Haley Veterans Hospital
      Tampa, Florida, United States
    • University of South Florida
      • Department of Molecular Pharmacology & Physiology
      Tampa, FL, United States
    • Wichita State University
      Wichita, Kansas, United States