Surgical excision promotes tumor growth and metastasis by promoting expression of MMP-9 and VEGF in a breast cancer model

Surgery is still the main curative therapeutic modality for breast cancer. Although surgery often results in the successful removal of the primary tumor, its process could increase the risk of metastases of residual cancer cells. Understanding of the connection between breast cancer metastasis and surgical wound will lead to the establishment of a proper treatment strategy for postoperative cancer patient. Aim: To study the influence of surgical procedure on the metastasis of primary breast cancer. Methods: We established MDA-MB-435 human breast cancer xenograft model. Levels of Pro-matrix metalloproteinase 9 (Pro-MMP-9) and vascular endothelial growth factor (VEGF) in host serum and tumors were tested at different time points with ELISA and zymography and correlated to tumor growth and postoperative metastasis. Results: Our study demonstrated surgical wound had promoting effect on tumor growth and pulmonary metastasis of human breast cells, if tumor cells remain in bodies. This effect might be related to the postoperative interaction of cancer and host cells, which resulted in expression of Pro-MMP-9. Surgical process could also increase the VEGF expression in tumor tissues. Conclusions: Surgical wound-produced host Pro-MMP-9 and tumor cell VEGF might be important mediators leading to metastasis of residual breast cancer after surgery.Хирургическое лечение до сих пор остается главным терапевтическим подходом при лечении больных раком молочной железы. Хотя хирургическое удаление опухоли в большинстве случаев достаточно эффективно, в то же время оно может увеличить риск метастазирования остаточных опухолевых клеток. Понимание связи между метастазированием при раке молочной железы и операционной раной позволит выбрать наилучшую стратегию постоперационного лечения. Цель: определить влияние хирургического вмешательства на метастазирование опухоли. Методы: была создана модель рака молочной железы человека в виде ксенотрансплантата MDA-MB-435. Уровень Pro-матричной металлопротеиназы 9 (Pro-MMP-9) и фактора роста эндотелия сосудов (VEGF) в сыворотке реципиента и опухолях оценивались в разные временные промежутки методом ELISA и зимографии. При этом определяли наличие корелляции между этими показа- и зимографии. При этом определяли наличие корелляции между этими показа и зимографии. При этом определяли наличие корелляции между этими показателями, ростом опухоли и постоперационными метастазами. Результаты: было показано, что операционная рана способствует росту опухоли молочной железы и ее метастазированию в легкие в случае, когда при удалении опухоли в ране остаются опухолевые клетки. Это может быть связано с постоперационным взаимодействием опухолевых и окружающих их нормальных клеток, которое приводит к экспрессии Pro-MMP-9. Удаление опухоли может также способствовать увеличению экспрессии VEGF опухолевыми клетками. Выводы: Pro-MMP-9, экспрессируемый нормальными клетками, окружающими постоперационную рану, а также VEGF, продуцируемый опухолевыми клетками, могут быть важными медиаторами метастазирования остаточных опухолевых клеток после хирургического вмешательства

The Empirical Mass-Luminosity Relation for Low Mass Stars

This work is devoted to improving empirical mass-luminosity relations and mass-metallicity-luminosity relation for low mass stars. For these stars, observational data in the mass-luminosity plane or the mass-metallicity-luminosity space subject to non-negligible errors in all coordinates with different dimensions. Thus a reasonable weight assigning scheme is needed for obtaining more reliable results. Such a scheme is developed, with which each data point can have its own due contribution. Previous studies have shown that there exists a plateau feature in the mass-luminosity relation. Taking into account the constraints from the observational luminosity function, we find by fitting the observational data using our weight assigning scheme that the plateau spans from 0.28 to 0.50 solar mass. Three-piecewise continuous improved mass-luminosity relations in K, J, H and V bands, respectively, are obtained. The visual mass-metallicity-luminosity relation is also improved based on our K band mass-luminosity relation and the available observational metallicity data.Comment: 8 pages, 2 figures. Accepted for publication in Astrophysics & Space Scienc

Nitrogen Addition and Warming Independently Influence the Belowground Micro-Food Web in a Temperate Steppe

Climate warming and atmospheric nitrogen (N) deposition are known to influence ecosystem structure and functioning. However, our understanding of the interactive effect of these global changes on ecosystem functioning is relatively limited, especially when it concerns the responses of soils and soil organisms. We conducted a field experiment to study the interactive effects of warming and N addition on soil food web. The experiment was established in 2006 in a temperate steppe in northern China. After three to four years (2009–2010), we found that N addition positively affected microbial biomass and negatively influenced trophic group and ecological indices of soil nematodes. However, the warming effects were less obvious, only fungal PLFA showed a decreasing trend under warming. Interestingly, the influence of N addition did not depend on warming. Structural equation modeling analysis suggested that the direct pathway between N addition and soil food web components were more important than the indirect connections through alterations in soil abiotic characters or plant growth. Nitrogen enrichment also affected the soil nematode community indirectly through changes in soil pH and PLFA. We conclude that experimental warming influenced soil food web components of the temperate steppe less than N addition, and there was little influence of warming on N addition effects under these experimental conditions

Oncolytic Viruses: Do They Have a Role in Anti-Cancer Therapy?

Oncolytic viruses are replication competent, tumor selective and lyse cancer cells. Their potential for anti-cancer therapy is based upon the concept that selective intratumoral replication will produce a potent anti-tumor effect and possibly bystander or remote cell killing, whilst minimizing normal tissue toxicity. Viruses may be naturally oncolytic or be engineered for oncolytic activity, and possess a host of different mechanisms to provide tumor selectivity. Clinical use of live replicating viruses is associated with a unique set of safety issues. Clinical experience has so far provided evidence of limited efficacy and a favourable toxicity profile. The interaction with the host immune system is complex. An anti-viral immune response may limit efficacy by rapidly clearing the virus. However, virally-induced cell lysis releases tumor associated antigens in a ‘dangerous’ context, and limited evidence suggests that this can lead to the generation of a specific anti-tumor immune response. Combination therapy with chemotherapy or radiotherapy represents a promising avenue for ongoing translation of oncolytic viruses into clinical practice. Obstacles to therapy include highly effective non-specific host mechanisms to clear virus following systemic delivery, immune-mediated clearance, and intratumoral barriers limiting virus spread. A number of novel strategies are now under investigation to overcome these barriers. This review provides an overview of the potential role of oncolytic viruses, highlighting recent progress towards developing effective therapy and asks if they are a realistic therapeutic option at this stage

Robustness of nonclassical superpositions states against decoherence

We make a comparative study of quadrature squeezing, photon-number distribution and Wigner function in a decayed quantum system. Specifically, for a field mode prepared initially in cat states interacting with a zero-temperature environment, we show that the rate of reduction of the nonclassical effects in this system is proportional to the occurrence of the decoherence process.Comment: 11 pages, 4 figure

Effects of rapid prey evolution on predator-prey cycles

We study the qualitative properties of population cycles in a predator-prey system where genetic variability allows contemporary rapid evolution of the prey. Previous numerical studies have found that prey evolution in response to changing predation risk can have major quantitative and qualitative effects on predator-prey cycles, including: (i) large increases in cycle period, (ii) changes in phase relations (so that predator and prey are cycling exactly out of phase, rather than the classical quarter-period phase lag), and (iii) "cryptic" cycles in which total prey density remains nearly constant while predator density and prey traits cycle. Here we focus on a chemostat model motivated by our experimental system [Fussmann et al. 2000,Yoshida et al. 2003] with algae (prey) and rotifers (predators), in which the prey exhibit rapid evolution in their level of defense against predation. We show that the effects of rapid prey evolution are robust and general, and furthermore that they occur in a specific but biologically relevant region of parameter space: when traits that greatly reduce predation risk are relatively cheap (in terms of reductions in other fitness components), when there is coexistence between the two prey types and the predator, and when the interaction between predators and undefended prey alone would produce cycles. Because defense has been shown to be inexpensive, even cost-free, in a number of systems [Andersson and Levin 1999, Gagneux et al. 2006,Yoshida et al. 2004], our discoveries may well be reproduced in other model systems, and in nature. Finally, some of our key results are extended to a general model in which functional forms for the predation rate and prey birth rate are not specified.Comment: 35 pages, 8 figure

Entropy-Corrected New Agegraphic Dark Energy Model in Horava-Lifshitz Gravity

In this work, we have considered the entropy-corrected new agegraphic dark energy (ECNADE) model in Horava-Lifshitz gravity in FRW universe. We have discussed the correspondence between ECNADE and other dark energy models such as DBI-essence,Yang-Mills dark energy, Chameleon field, Non-linear electrodynamics field and hessence dark energy in the context of Horava-Lifshitz gravity and reconstructed the potentials and the dynamics of the scalar field theory which describe the ECNADE.Comment: 12 page

A Study of Cosmic Ray Secondaries Induced by the Mir Space Station Using AMS-01

The Alpha Magnetic Spectrometer (AMS-02) is a high energy particle physics experiment that will study cosmic rays in the $\sim 100 \mathrm{MeV}$ to $1 \mathrm{TeV}$ range and will be installed on the International Space Station (ISS) for at least 3 years. A first version of AMS-02, AMS-01, flew aboard the space shuttle \emph{Discovery} from June 2 to June 12, 1998, and collected $10^8$ cosmic ray triggers. Part of the \emph{Mir} space station was within the AMS-01 field of view during the four day \emph{Mir} docking phase of this flight. We have reconstructed an image of this part of the \emph{Mir} space station using secondary $\pi^-$ and $\mu^-$ emissions from primary cosmic rays interacting with \emph{Mir}. This is the first time this reconstruction was performed in AMS-01, and it is important for understanding potential backgrounds during the 3 year AMS-02 mission.Comment: To be submitted to NIM B Added material requested by referee. Minor stylistic and grammer change

The discovery of Hepatocyte Growth Factor (HGF) and its significance for cell biology, life sciences and clinical medicine

It has been more than 25 years since HGF was discovered as a mitogen of hepatocytes. HGF is produced by stromal cells, and stimulates epithelial cell proliferation, motility, morphogenesis and angiogenesis in various organs via tyrosine phosphorylation of its receptor, c-Met. In fetal stages, HGF-neutralization, or c-Met gene destruction, leads to hypoplasia of many organs, indicating that HGF signals are essential for organ development. Endogenous HGF is required for self-repair of injured livers, kidneys, lungs and so on. In addition, HGF exerts protective effects on epithelial and non-epithelial organs (including the heart and brain) via anti-apoptotic and anti-inflammatory signals. During organ diseases, plasma HGF levels significantly increased, while anti-HGF antibody infusion accelerated tissue destruction in rodents. Thus, endogenous HGF is required for minimization of diseases, while insufficient production of HGF leads to organ failure. This is the reason why HGF supplementation produces therapeutic outcomes under pathological conditions. Moreover, emerging studies delineated key roles of HGF during tumor metastasis, while HGF-antagonism leads to anti-tumor outcomes. Taken together, HGF-based molecules, including HGF-variants, HGF-fragments and c-Met-binders are available as regenerative or anti-tumor drugs. Molecular analysis of the HGF-c-Met system could provide bridges between basic biology and clinical medicine

Cosmic-ray positron fraction measurement from 1 to 30 GeV with AMS-01

A measurement of the cosmic ray positron fraction e+/(e+ + e-) in the energy range of 1-30 GeV is presented. The measurement is based on data taken by the AMS-01 experiment during its 10 day Space Shuttle flight in June 1998. A proton background suppression on the order of 10^6 is reached by identifying converted bremsstrahlung photons emitted from positrons