The environmental model segment approach for estimating potential environmental concentrations

Frische, R.; Klöpffer, Walter; Rippen, Gerd; Günther, K.

doi:10.1016/0147-6513(84)90004-6

Cited by 18 publications

(3 citation statements)

References 19 publications

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“…AP‐1 binding assays in nuclear extracts were performed with end [α‐ 32 P] adenosine triphosphate labeled double‐stranded AP‐1 oligonucleotides probe, and the electrophoretic mobility shift assay was carried out. 293T cells were treated with various concentration of IAX, and nuclear extracts were prepared as described previously 29, 30. Nuclear proteins (5 μg) were incubated with labeled AP‐1 probe on ice for 30 min, and the DNA‐protein complexes were separated on a 6% acrylamide gel.…”

Section: Methodsmentioning

confidence: 99%

Isoalvaxanthone inhibits colon cancer cell proliferation, migration and invasion through inactivating Rac1 and AP‐1

Wang

Kuang

Pan

et al. 2010

Intl Journal of Cancer

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Isoalvaxanthone (IAX) is a bioactive xanthone isolated from Cudrania cochinchinensis (Lour.). However, the function and mechanism of this compound in cancer migration and invasion have not been elucidated to date. In this study, we found that IAX could suppress various steps of tumor metastasis including proliferation, migration and invasion in a dose-dependent manner on colorectal cancer cells. Especially matrix metalloproteinase 2 (MMP-2), the pivotal factor in cancer invasion, was suppressed both on activation and expression after treated with IAX. To understand the underlying mechanism of IAX on the inhibitory effect of proliferation, migration and invasion, we demonstrated that IAX could significantly inhibit the activation of Rac1 but has undetectable effect on GTP-RhoA, GTP-Cdc42 and the phosphorylation of ERK1/2, p38 MAPK and JNK. Moreover, IAX showed little influence on the transcriptional activity of nuclear transcription factor jB (NF-jB) but strongly inhibited that of activator protein-1 (AP-1), which is the downstream transcriptional factor of Rac1. Together, our results indicate that IAX exerts anticancer effect in SW620 cells by targeting MMP-2 via regulating the activity of Rac1 and AP-1. These results are the first to reveal the function of IAX in tumor metastasis and its underlying molecular mechanism, thus suggest IAX to be a promising antimetastatic agent.Colorectal carcinoma is the third most common form of cancer and the second leading cause of morbidity and mortality in the world.1 Metastasis, a main cause of death in cancer patients, contributes to the high mortality of colorectal cancer, despite most early stage colorectal cancer is curable with surgical resection. In metastasis, malignant tumor cells moved from the primary tumor to a secondary distant organ through a complex multistage process involving the coordination of several signaling pathways that allow changes in cell morphology, migration and invasion.2,3 During the process of metastasis, degradation of the extracellular matrix (ECM) by proteases such as matrix metalloproteinases (MMPs) is important. MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are the most vital proteases for the degradation of the main constituent of the basement membrane, type IV collagen and are, therefore, pivotal for cancer invasion and metastasis. 4 The Rho family proteins (RhoA, Rac1 and Cdc42) are small GTP-binding proteins with a distinct function in cell survival, cytoskeleton organization, adhesion and motility, thus become important targets of cancer chemotherapy. 5,6 It is now known that these biological activities are coordinated by the concerted action of different Rho/Rac subfamily members. For instance, RhoA function is required for the initial formation of the lamellipodia and the establishment of focal adhesions and stress fibers, Rac1 promotes membrane ruffles and lamellipodia and Cdc42 trigger filopodia in the leading edge of migrating cells.7 Small GTPases are also molecular switches that trigger signaling cascades in response to upstrea...

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Section: Methodsmentioning

confidence: 99%

Isoalvaxanthone inhibits colon cancer cell proliferation, migration and invasion through inactivating Rac1 and AP‐1

Wang

Kuang

Pan

et al. 2010

Intl Journal of Cancer

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“…Multimedia mass balance modelling was initiated in the early 1980s by Mackay and co-workers [2,[33][34][35][36]. The example was soon followed by others [11,[37][38][39]. In Europe, the model SimpleBox used in The Netherlands was adopted as the basis for the risk assessment model EUSES [12,13].…”

Section: Multimedia Modellingmentioning

confidence: 99%

Fate and Transport of Contaminants

2007

Encyclopedia of Environment and Society

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Release of toxic chemicals into the environment cannot always be avoided completely. As a result organisms, man included, will be exposed to chemicals via the environment. Given the release of certain chemicals into the environment, their exposure concentrations in air, water and soil would depend on the rates at which they are removed from the environment. This chapter deals with the transport and transformation processes that affect concentrations in the environment, with emphasis on the modeller's perspective. Being interested primarily in the effects that processes have on concentrations of chemicals in environmental media, we focus on a quantitative description of the rates at which losses from the environment take place, and on how these rates differ for different chemicals. We systematically formulate process rate constants for each transport or transformation process. Eventually, the rate constants combine into a mass balance model which allows us to describe and predict how releases into the environment result in exposure concentrations of organisms. This text is taken largely from chapters 3 and 4 of the textbook by Van Leeuwen and Vermeire [1], the authors of which are kindly acknowledged. 1 t 1/2 2 t 1/2 3 t 1/2 0.5 M 0 0.25 M 0 1 M 0 0.125 M 0 t 0 Fate and Transport of Contaminants Ecological Impacts of Toxic Chemicals 15where K oc = organic carbon referenced solids-water partition coefficient (L/kg) a, b = constants, specific for chemical classes Given a value of K p , the extent to which partitioning from water to solids occurs depends on the amount of solids present. At equilibrium, the mass fraction of chemical dissolved in water  dissolved can be calculated aswhere TSS = mass concentration of suspended solids in water (= ~ 10 -5 kg/L)Normalization to the organic carbon content of particulate matter has become standard procedure in this field of research. This procedure is based on the experimental observation that the K p of organic chemicals is often proportional to the organic matter content of the solid phase. The estimation method was derived originally for hydrophobic chemicals [3]. The method was extended to apply to various other classes of non-ionic organic chemicals [4] and, more recently, to ionizing organic acids and bases [5]. The method cannot be applied to metals and other inorganic ionizing substances.Solids-water partition coefficients are commonly reported in units L/kg. The physical meaning of this dimension can be understood by reading it as "the volume of water (L) which contains the same amount of the chemical as one kilogram of solid material does". For many purposes, however, we are not just interested in the concentration ratio, but also in the mass distribution of the chemical over the phases. Obviously, this distribution depends on both the partition coefficient and the relative volumes of the phases. In surface water, the solids-water ratio is much smaller than in sediment and soil systems. As a result, the extent of partitioning of a certain chemical into the partic...

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“…The environment is treated as a set of compartments that are homogeneous subsystems exchanging gas, water, solids, and chemical contaminants with other adjacent compartments. Efforts to develop regional/global contaminant models based on mass balance equations emerged in the late 1970s with the publications of the first edition of Chemodynamics (Thibodeaux, 1979), the environmental segment model (Klöpffer, 1978;Frische et al,1984) and the seminal papers by Mackay (1979) and Mackay andPaterson (1981, 1982) describing the application of fugacity principles 5 to environmental problems. By the late 1980's multimedia modelling had become more established and was the subject of several reviews, international workshops and studies (Cohen, 1986;PUC, 1986;Allen, 1989;NAS, 1994;Cowan et al, 1995).…”

Section: Increasing Complexity By Model Structure (Level I To Level Iv)mentioning

confidence: 99%

Guidance Document on the Use of Multimedia Models for Estimating Overall Environmental Persistance and Long-Range Transport

2004

OECD Series on Testing and Assessment

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The environmental model segment approach for estimating potential environmental concentrations

Cited by 18 publications

References 19 publications

Isoalvaxanthone inhibits colon cancer cell proliferation, migration and invasion through inactivating Rac1 and AP‐1

Isoalvaxanthone inhibits colon cancer cell proliferation, migration and invasion through inactivating Rac1 and AP‐1

Fate and Transport of Contaminants

Guidance Document on the Use of Multimedia Models for Estimating Overall Environmental Persistance and Long-Range Transport

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