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MET targeted therapy for lung cancer: clinical development and future directions
Feng Y, Ma PC
Lung Cancer: Targets and Therapy , 2012, DOI: http://dx.doi.org/10.2147/LCTT.S23423
Abstract: argeted therapy for lung cancer: clinical development and future directions Review (2143) Total Article Views Authors: Feng Y, Ma PC Published Date August 2012 Volume 2012:3 Pages 53 - 67 DOI: http://dx.doi.org/10.2147/LCTT.S23423 Received: 19 March 2012 Accepted: 08 May 2012 Published: 10 August 2012 Yan Feng,1,2 Patrick C Ma1–3 1Translational Hematology and Oncology Research, 2Solid Tumor Oncology, 3Aerodigestive Oncology Translational Research, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA Abstract: MET, the receptor for hepatocyte growth factor, has been identified as a novel promising target in various human malignancies, including lung cancer. Research studies have demonstrated that MET signaling plays important physiologic roles in embryogenesis and early development, whereas its deregulation from an otherwise quiescent signaling state in mature adult tissues can lead to upregulated cell proliferation, survival, scattering, motility and migration, angiogenesis, invasion, and metastasis in tumorigenesis and tumor progression. The MET pathway can be activated through ligand (hepatocyte growth factor, HGF) or MET receptor overexpression, genomic amplification, MET mutations, and alternative splicing. A number of novel therapeutic agents that target the MET/hepatocyte growth factor pathway have been tested in early-phase clinical studies with promising results. Phase III studies of MET targeting agents have recently been initiated. This paper will review the MET signaling pathway and biology in lung cancer, and the recent clinical development and advances of MET/hepatocyte growth factor targeting agents. Emphasis will be placed on discussing various unanswered issues and key strategies needed to optimize further clinical development of MET targeting personalized lung cancer therapy.
Pyrite Oxidation under initially neutral pH conditions and in the presence of Acidithiobacillus ferrooxidans and micromolar hydrogen peroxide
Y. Ma,C. Lin
Biogeosciences Discussions , 2012, DOI: 10.5194/bgd-9-557-2012
Abstract: Hydrogen peroxide (H2O2) at a micromolar level played a role in the microbial surface oxidation of pyrite crystals under initially neutral pH. When the mineral-bacteria system was cyclically exposed to 50 μM H2O2, the colonization of extit{Acidithiobacillus ferrooxidans} onto the mineral surface was markedly enhanced, as compared to the control (no added H2O2). This can be attributed to the effects of H2O2 on increasing the roughness of the mineral surfaces, as well as the acidity and Fe2+ concentration at the mineral-solution interfaces. All of these effects tended to create more favourable nano- to micro-scale environments in the mineral surfaces for the cell adsorption. However, higher H2O2 levels inhibited the attachment of cells onto the mineral surfaces, possibly due to the oxidative stress in the bacteria when they approached the mineral surfaces where high levels of free radicals are present as a result of Fenton-like reactions. The more aggressive nature of H2O2 as an oxidant caused marked surface flaking of the mineral surface. The XPS results suggest that H2O2 accelerated the oxidation of pyrite-S and consequently facilitated the overall corrosion cycle of pyrite surfaces. This was accompanied by pH drop in the solution in contact with the pyrite cubes.
MET targeted therapy for lung cancer: clinical development and future directions
Feng Y,Ma PC
Lung Cancer: Targets and Therapy , 2012,
Abstract: Yan Feng,1,2 Patrick C Ma1–31Translational Hematology and Oncology Research, 2Solid Tumor Oncology, 3Aerodigestive Oncology Translational Research, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USAAbstract: MET, the receptor for hepatocyte growth factor, has been identified as a novel promising target in various human malignancies, including lung cancer. Research studies have demonstrated that MET signaling plays important physiologic roles in embryogenesis and early development, whereas its deregulation from an otherwise quiescent signaling state in mature adult tissues can lead to upregulated cell proliferation, survival, scattering, motility and migration, angiogenesis, invasion, and metastasis in tumorigenesis and tumor progression. The MET pathway can be activated through ligand (hepatocyte growth factor, HGF) or MET receptor overexpression, genomic amplification, MET mutations, and alternative splicing. A number of novel therapeutic agents that target the MET/hepatocyte growth factor pathway have been tested in early-phase clinical studies with promising results. Phase III studies of MET targeting agents have recently been initiated. This paper will review the MET signaling pathway and biology in lung cancer, and the recent clinical development and advances of MET/hepatocyte growth factor targeting agents. Emphasis will be placed on discussing various unanswered issues and key strategies needed to optimize further clinical development of MET targeting personalized lung cancer therapy.Keywords: MET, HGF, lung cancer, targeted therapy
Scaling of Anisotropic Flows in Intermediate Energy and Ultra-relativistic Heavy Ion Collisions
Y. G. Ma
Physics , 2006, DOI: 10.1063/1.2398863
Abstract: Anisotropic flows ($v_2$ and $v_4$) of hadrons and light nuclear clusters are studied by a partonic transport model and nucleonic transport model, respectively, in ultra-relativistic and intermediate energy heavy ion collisions. Both number-of-constituent-quark scaling of hadrons, especially for $\phi$ meson which is composed of strange quarks, and number-of-nucleon scaling of light nuclear clusters are discussed and explored for the elliptic flow ($v_2$). The ratios of $v_4/v_2^2$ of hadrons and nuclear clusters are, respectively, calculated and they show different constant values which are independent of transverse momentum. The above phenomena can be understood, respectively, by the coalescence mechanism in quark-level or nucleon-level.
Statistical nature of cluster emission in nuclear liquid phase
Y. G. Ma
Physics , 2002,
Abstract: The emission of nuclear clusters is investigated within the framework of isospin dependent lattice gas model and classical molecular dynamics model. It is found that the emission of individual cluster which is heavier than proton is almost Poissonian except near the liquid gas phase transition point and the thermal scaling is observed by the linear Arrhenius plots which is made from the average multiplicity of each cluster versus the inverse of temperature in the nuclear liquid phase. It indicates of a statistical nature of such cluster emission in the models. The "emission barriers" which are the slopes of the Arrhenius plots are extracted as a function of the mass or charge number and fitted by the formula embodied with the contributions of the surface energy and Coulomb interaction. The possible influences of the source size, Coulomb interaction and "freeze-out" density and related physical implications are discussed.
Cluster emission and phase transition behaviours in nuclear disassembly
Y. G. Ma
Physics , 2002, DOI: 10.1088/0954-3899/27/12/307
Abstract: The features of the emissions of light particles (LP), charged particles (CP), intermediate mass fragments (IMF) and the largest fragment (MAX) are investigated for $^{129}Xe$ as functions of temperature and 'freeze-out' density in the frameworks of the isospin-dependent lattice gas model and the classical molecular dynamics model. Definite turning points for the slopes of average multiplicity of LP, CP and IMF, and of the mean mass of the largest fragment ($A_{max}$) are shown around a liquid-gas phase transition temperature and while the largest variances of the distributions of LP, CP, IMF and MAX appear there. It indicates that the cluster emission rate can be taken as a probe of nuclear liquid--gas phase transition. Furthermore, the largest fluctuation is simultaneously accompanied at the point of the phase transition as can be noted by investigating both the variances of their cluster multiplicity or mass distributions and the Campi scatter plots within the lattice gas model and the molecular dynamics model, which is consistent with the result of the traditional thermodynamical theory when a phase transition occurs.
Poissonian reducibility and thermal scaling within the lattice gas model and molecular dynamics model
Y. G. Ma
Physics , 2000,
Abstract: The emission of clusters in the nuclear disassembly is investigated within the framework of isospin dependent lattice gas model and classical molecular dynamics model. As observed in the recent experimental data, it is found that the emission of individual cluster is poissonian and thermal scaling is observed in the linear Arrhenius plots made from the average multiplicity of each cluster. The mass, isotope and charge dependent "emission barriers" are extracted from the slopes of the Arrhenius plots and their possible physical implications are investigated.
Zipf's Law in the Liquid Gas Phase Transition of Nuclei
Y. G. Ma
Physics , 2000,
Abstract: Zipf's law in the field of linguistics is tested in the nuclear disassembly within the framework of isospin dependent lattice gas model. It is found that the average cluster charge (or mass) of rank $n$ in the charge (or mass) list shows exactly inversely to its rank, i.e., there exists Zipf's law, at the phase transition temperature. This novel criterion shall be helpful to search the nuclear liquid gas phase transition experimentally and theoretically. In addition, the finite size scaling of the effective phase transition temperature at which the Zipf's law appears is studied for several systems with different mass and the critical exponents of $\nu$ and $\beta$ are tentatively extracted.
Moment Analysis and Zipf Law
Y. G. Ma
Physics , 2006, DOI: 10.1140/epja/i2006-10119-4
Abstract: The moment analysis method and nuclear Zipf's law of fragment size distributions are reviewed to study nuclear disassembly. In this report, we present a compilation of both theoretical and experimental studies on moment analysis and Zipf law performed so far. The relationship of both methods to a possible critical behavior or phase transition of nuclear disassembly is discussed. In addition, scaled factorial moments and intermittency are reviewed.
Experimental observables on nuclear liquid gas phase transition
Y. G. Ma
Physics , 2006,
Abstract: Progress on nuclear liquid gas phase transition (LGPT) or critical behavior has been simply reviewed and some signals of LGPT in heavy ion collisions, especially in NIMROD data, are focused. These signals include the power-law charge distribution, the largest fluctuation of the fragment observables, the nuclear Zipf law, caloric curve and critical exponent analysis etc.
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