Paclitaxel is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer.
Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner.
Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell.
Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.
Ref: www.drugbank.ca
Aspirin (acetylsalicylic acid) is a salicylate drug used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever and as an anti-inflammatory medication. Aspirin also has an antiplatelet effect by inhibiting the production of thromboxane, which under normal circumstances binds platelet molecules together to repair damaged blood vessels.
This is why aspirin is used in long-term, low doses to prevent heart attacks, strokes, and blood clot formation in people at high risk for developing blood clots. It has also been established that low doses of aspirin may be given immediately after a heart attack to reduce the risk of another heart attack or of the death of cardiac tissue.
Aspirin was the first discovered member of the class of drugs known as non-steroidal anti-inflammatory drugs, not all of which are salicylates, although they all have similar effects and most have inhibition of the enzyme cyclooxygenase as their mechanism of action. Today, aspirin is one of the most widely used medications in the world, with an estimated 40,000 tonnes of it being consumed each year.
Fatostatin, a small molecule earlier found to have both anti-fat and anti-cancer abilities works as a literal turnoff for fat-making genes, according to a new report in the August 28th issue of the journal Chemistry and Biology, a Cell Press journal.
Fatostatin blocks a well known master controller of fat synthesis known as SREBP. That action in mice that are genetically prone to obesity causes the animals to become leaner. It also lowers the amount of fat in their livers, along with their blood sugar and cholesterol levels.
Unlike cholesterol-lowering statins in use today, which block a single enzyme in the pathway, the chemical hits fat from the very beginning. In doing so, fatostatin influences many of the genes involved in fat production and in various aspects of metabolic syndrome – a collection of risk factors including obesity, high cholesterol and insulin resistance in one go.
Studies in cell culture showed that fatostatin, previously known only as 125B11, significantly lowers the activity of 63 genes, including 34 directly associated with fatty acid or cholesterol synthesis. Many of those were known to be under the control of SREBP.
More detailed analysis reveals that the drug candidate blocks SREBP by preventing it from becoming active and entering the nucleus, where it would otherwise switch on the fat-making program. It operates by binding another protein (called SCAP), which serves as SREBP's escort into the nucleus.
Obese mice injected with fatostatin show noticeable reductions in their weight despite little difference in their eating habits. After four weeks of treatment, the animals weighed 12 percent less and had 70 percent lower blood sugar levels. Their cholesterol levels (both LDL and HDL) were down too. The concentration of fatty acids in their blood was actually higher, a sign of their greater demand for fat to burn.
While the livers of the obese mice were heavy and pale with fat, treated animals' livers were more than 30 percent lighter and were a healthy-looking red.
Although less obvious, the SREBP-blocking ability might also explain the molecule's earlier reported effects against prostate cancer cells in culture as well. Cells need fatty acids and cholesterol to build their cell membranes and continue growing, they explain.
Fatostatin is not the first molecule to act on SREBP, according to the researchers, but it appears to do so in a somewhat different way than those described previously. Many steps remain, but they are optimistic that fatostatin could prove to be clinically useful in the context of obesity, and perhaps cardiovascular disease and diabetes as well.
Researchers responsible for the study include Shinji Kamisuki, Kyoto University, Uji, Kyoto, Japan; Qian Mao, Baylor College of Medicine, Houston, TX; Lutfi Abu-Elheiga, Baylor College of Medicine, Houston, TX; Ziwei Gu, Baylor College of Medicine, Houston, TX; Akira Kugimiya, Kyoto University, Uji, Kyoto, Japan; Youngjoo Kwon, Baylor College of Medicine, Houston, TX; Tokuyuki Shinohara, Kyoto University, Uji, Kyoto, Japan; Yoshinori Kawazoe, Kyoto University, Uji, Kyoto, Japan; Shin-ichi Sato, Baylor College of Medicine, Houston, TX; Koko Asakura, Baylor College of Medicine, Houston, TX; Hea-Young Park Choo, Kyoto University, Uji, Kyoto, Japan; Juro Sakai, University of Tokyo, Tokyo, Japan; Salih J. Wakil, Baylor College of Medicine, Houston, TX; and Motonari Uesugi, Kyoto University, Uji, Kyoto, Japan, Baylor College of Medicine, Houston, TX.
We are proud to let you know that this week hBar Solutions ApS, the company behind hBar Lab, has been accepted to the Accelerace (http://www.accelerace.dk/) program.
Accelerace is a fast-action, internationally-focused business development program for potential high-growth small companies & start-ups in Denmark. Accelerace will help hBar Solutions in growing and providing to its customers even better products and services.
In fact the Accelerace program puts the entrepreneurs at the center of this process, providing them with the tools and know-how to propel their business idea forward by answering the following questions:
- Who has the biggest need for the offering?
- Where does the offering currently fit into the market?
- Who can we best serve first in the selected market?
