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Although many clinical studies have been done with anticancer drugs alone, most of those carried out with combined cancer chemotherapy have been based on a fundamental assumption that the drug absorption and the distribution in the tumors were similar to those in normal tissues. However, recent studies have shown that drug distribution in tumor tissues may be quite different from that in normal tissues: tumor cells often have good capacities for anticancer drug uptake, while there are few drugs able to enter in substantial amounts and distribute throughout the cells; tumor cells can alter the rate and extent of uptake and efflux of anticancer drugs depending on the balance between these processes and changes in the cellular and extra cellular environment, such as oxygenation, pH or the existence of other metabolic abnormalities. These alterations can alter the efficacy and toxicity of anticancer drugs, and may also change the pharmacokinetics and pharmacodynamics of the drugs thus affecting their toxicity and antitumor effects. The term “drug resistance” must be used to describe this situation, and should not be used to describe only intrinsic or acquired resistance to anticancer drugs. In this review, the alterations of drug delivery by cancer cells are discussed in relation to the mechanisms, characteristics and correlations of these changes to the resistance to anticancer drugs, and their impact on the antitumor effects of the drugs as evaluated in terms of chemosensitivity tests and anticancer effects in vivo. These alterations can be divided into three types: i) increased drug uptake, ii) altered drug efflux, and iii) changes in metabolism. We also address the need for additional studies to elucidate the role of drug delivery in the clinical efficacy of anticancer chemotherapy./*
* Copyright (c) 2013 Trond Myklebust
Croatian dubbing recordings at IIXS.Grote kust in perfect Guinness weather
The Grote Kust is a popular attraction in our region. Today we had perfect weather and did some Grote Kust spotting.
On the tourist bus we saw a lot of stars at the front. Following them, one can see several windmills and their windpark. Besides a lot of smaller windmills, there are also a few large windmills.
The Grote Kust is made out of countless big and small rocks. It is located on a peninsula in the Wadden Sea. Because of the shape of the peninsula the Grote Kust is also called the Zeekoop. The Zeekoop is located east of the Wadden Sea and consequently north of the Wadden Sea National Park.
The Grote Kust (Dutch for Large Coast) is one of our most visited places. Ever since it was built in 2006, almost 400,000 people have visited the Grote Kust. The windmills of the Grote Kust have been built since 1730. The windmills were originally designed to grind grain. They are still operational and produce a lot of electricity. The windpark consists of 4 large windmills and 11 small windmills.
When it is windy it is great to look for the stars at the front. The Grote Kust is also famous for the crabs and other creatures that roam around the beach. The best time to catch a glimpse of the crabs is in the early morning. The crabs are attracted by the sand-filled flipper of the windmills. They have also been known to collect seaweed.
The windmills at the Grote Kust are not allowed to be removed. Therefore several statues have been erected in the area. These are famous icons of the Netherlands. There is the Amstel Idol, the Vloot Idol, a Globe Idol, a Statue of Bartolomeus Van der Weijde and the Statue of Femke Sijmons.
The Grote Kust is a beautiful place and a popular place. We hope you enjoyed this video as much as we enjoyed shooting it. You can watch the video again and again at this location on our channel.
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