June 15, 2013 ? A drug approved in Europe to treat osteoporosis has now been shown to stop the growth of breast cancer cells, even in cancers that have become resistant to current targeted therapies, according to a Duke Cancer Institute study.
The findings, presented June 15, 2013, at the annual Endocrine Society meeting in San Francisco, indicate that the drug bazedoxifene packs a powerful one-two punch that not only prevents estrogen from fueling breast cancer cell growth, but also flags the estrogen receptor for destruction.
"We found bazedoxifene binds to the estrogen receptor and interferes with its activity, but the surprising thing we then found was that it also degrades the receptor; it gets rid of it," said senior author Donald McDonnell, PhD, chair of Duke's Department of Pharmacology and Cancer Biology.
In animal and cell culture studies, the drug inhibited growth both in estrogen-dependent breast cancer cells and in cells that had developed resistance to the anti-estrogen tamoxifen and/or to the aromatase inhibitors, two of the most widely used types of drugs to prevent and treat estrogen-dependent breast cancer. Currently, if breast cancer cells develop resistance to these therapies, patients are usually treated with toxic chemotherapy agents that have significant side effects.
Bazedoxifene is a pill that, like tamoxifen, belongs to a class of drugs known as specific estrogen receptor modulators (SERMs). These drugs are distinguished by their ability to behave like estrogen in some tissues, while significantly blocking estrogen action in other tissues. But unlike tamoxifen, bazedoxifene has some of the properties of a newer group of drugs, known as selective estrogen receptor degraders, or SERDs, which can target the estrogen receptor for destruction.
"Because the drug is removing the estrogen receptor as a target by degradation, it is less likely the cancer cell can develop a resistance mechanism because you are removing the target," said lead author Suzanne Wardell, PhD, a research scientist working in McDonnell's lab.
Many investigators had assumed that once breast cancer cells developed resistance to tamoxifen, they would be resistant to all drugs that target the estrogen receptor, McDonnell explained.
"We discovered that the estrogen receptor is still a good target, even after it resistance to tamoxifen has developed," he said.
The investigators tested a variety of breast cancer cell types, including tamoxifen-sensitive cells that are resistant to the drug lapatinib, another targeted therapy that is used to treat patients with advanced breast cancer whose tumors contain the mutant HER2 gene. These cells had previously been shown to reactivate estrogen signaling in order to acquire drug resistance. In this cell type, bazedoxifene also potently inhibited cell growth.
Paradoxically, in bone tissue, bazedoxifene mimics the action of estrogen, helping protect it from destruction. Because bazedoxifene has already undergone safety and efficacy studies as a treatment for osteoporosis, it may be a viable near-term option for patients with advanced breast cancer whose tumors have become resistant to other treatment options, Wardell reported. In clinical trials, the most often reported side effect was hot flashes in the bazedoxifene treatment groups.
The study was funded by a research grant from Pfizer Pharmaceuticals, maker of bazedoxifene.
In addition to Wardell and McDonnell, Erik Nelson and Christina Chao of the Department of Pharmacology and Cancer Biology, Duke University School of Medicine, contributed to the research.
For youtube videos, paste embed code directly in the text box
-
Members do not need to provide an address
-
Rate Article
1
2
3
4
5
Total votes: 0
Select Comment Validation Method Member Name/URL (Guest) FaceBook (Guest) Member Commenting:
Authenticate with Facebook before submitting
OR
Make your LabSpaces comments count. Start earning LabSpaces points by becoming a member! Learn more. Please verify that you are human:Register for LabSpaces Make your LabSpaces comments count. Start earning LabSpaces points by becoming a member! Learn more.
Please authenticate before trying to post a comment.
If you would like to remain anonymous, please enter a new name and link below
Children are impossible to please, no matter now many Lunchables you ply them with. But even the most ungrateful tykes will appreciate getting one of Mores stunning Petitpierre kids bikes crafted from carbon fiber so they're easier to ride and maneuver.
Featuring everything from built-in LED safety lights, to a clever footrest built into the frame for kids just learning to ride, the bike's curvy design gives it a lower center of gravity which makes mastering the two-wheel balancing act a little easier. And at just under seven pounds kids can easily lift it over curbs or other obstacles they're too small to tackle.
The only catch? A $2,000 price tag that will probably have parents refusing to let their kids actually ride the Petitpierre so that it can be handed down for generations.
June 10, 2013 ? A single cell in our body is composed of thousands of millions of different biomolecules that work together in an extremely well-coordinated way. Likewise, many biological and biochemical reactions occur only if molecules are present at very high concentrations. Understanding how all these molecules interact with each other is key to advancing our knowledge in molecular and cell biology.
This knowledge is of central and fundamental importance in the quest for the detection of the earliest stages of many human diseases. As such, one of ultimate goals in Life Sciences and Biotechnology is to observe how individual molecules work and interact with each other in these very crowded environments. Unfortunately, detecting one molecule amongst millions of neighbouring molecules has been technically impossible until now. The key to successfully detecting the single molecule lies in the conception and production of a working device that shrinks the observation region to a tiny size that is comparable to the size of the molecule itself, i.e. only a few nanometres.
Researchers at the Fresnel Institute in Marseille and ICFO-the Institute for Photonic Sciences in Barcelona report in Nature Nanotechnology the design and fabrication of the smallest optical device, capable of detecting and sensing individual biomolecules at concentrations that are similar to those found in the cellular context. The device called "antenna-in-a-box" consists on a tiny dimer antenna made out of two gold semi-spheres, separated from each other by a gap as small as 15nm. Light sent to this antenna is enormously amplified in the gap region where the actual detection of the biomolecule of interest occurs. Because amplification of the light is confined to the dimensions of the gap, only molecules present in this tiny region are detected. A second trick that the researchers used to make this device work was to embed the dimer antennas inside boxes also of nanometric dimensions. "The box screens out the unwanted "noise" of millions of other surrounding molecules, reducing the background and improving as a whole the detection of individual biomolecules.," explains Jerome Wenger from Fresnel Institute. When tested under different sample concentrations, this novel antenna-in-box device allowed for 1100-fold fluorescence brightness enhancement together with detection volumes down to 58 zeptoliters (1 zL = 10-21L), i.e., the smallest observation volume in the world.
The antenna-in-a-box offers a highly efficient platform for performing a multitude of nanoscale biochemical assessments with single molecule sensitivity at physiological conditions. It could be used for ultrasensitive sensing of minute amounts of molecules, becoming an excellent early diagnosis device for biosensing of many disease markers. "It can also be used as an ultra-bright optical nanosource to illuminate molecular processes in living cells and ultimately visualize how individual biomolecules interact with each other. This brings us closer to the long awaited dream of biologists," concludes ICFO researcher Prof. Maria Garcia-Parajo.
Share this story on Facebook, Twitter, and Google:
Other social bookmarking and sharing tools:
Story Source:
The above story is reprinted from materials provided by ICFO-The Institute of Photonic Sciences, via EurekAlert!, a service of AAAS.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
Deep Punj, Mathieu Mivelle, Satish Babu Moparthi, Thomas S. van Zanten, Herv? Rigneault, Niek F. van Hulst, Mar?a F. Garc?a-Paraj?, J?r?me Wenger. A plasmonic ?antenna-in-box? platform for enhanced single-molecule analysis at micromolar concentrations. Nature Nanotechnology, 2013; DOI: 10.1038/nnano.2013.98
Note: If no author is given, the source is cited instead.
Mysterious monument found beneath the Sea of GalileePublic release date: 10-Jun-2013 [ | E-mail | Share ]
Contact: George Hunka ghunka@aftau.org 212-742-9070 American Friends of Tel Aviv University
Tel Aviv University research says unique structure is the product of skilled construction
The shores of the Sea of Galilee, located in the North of Israel, are home to a number of significant archaeological sites. Now researchers from Tel Aviv University have found an ancient structure deep beneath the waves as well.
Researchers stumbled upon a cone-shaped monument, approximately 230 feet in diameter, 39 feet high, and weighing an estimated 60,000 tons, while conducting a geophysical survey on the southern Sea of Galilee, reports Prof. Shmulik Marco of TAU's Department of Geophysics and Planetary Sciences. The team also included TAU Profs. Zvi Ben-Avraham and Moshe Reshef, and TAU alumni Dr. Gideon Tibor of the Oceanographic and Limnological Research Institute.
Initial findings indicate that the structure was built on dry land approximately 6,000 years ago, and later submerged under the water. Prof. Marco calls it an impressive feat, noting that the stones, which comprise the structure, were probably brought from more than a mile away and arranged according to a specific construction plan.
Dr. Yitzhak Paz of the Antiquities Authority and Ben-Gurion University says that the site, which was recently detailed in the International Journal of Nautical Archaeology, resembles early burial sites in Europe and was likely built in the early Bronze Age. He believes that there may be a connection to the nearby ancient city of Beit Yerah, the largest and most fortified city in the area.
Ancient structure revealed by sonar
The team of researchers initially set out to uncover the origins of alluvium pebbles found in this area of the Sea of Galilee, which they believe were deposited by the ancient Yavniel Creek, a precursor to the Jordan River south of the Sea of Galilee. While using sonar technology to survey the bottom of the lake, they observed a massive pile of stones in the midst of the otherwise smooth basin.
Curious about the unusual blip on their sonar, Prof. Marco went diving to learn more. A closer look revealed that the pile was not a random accumulation of stones, but a purposefully-built structure composed of three-foot-long volcanic stones called basalt. Because the closest deposit of the stone is more than a mile away, he believes that they were brought to the site specifically for this structure.
To estimate the age of the structure, researchers turned to the accumulation of sand around its base. Due to a natural build-up of sand throughout the years, the base is now six to ten feet below the bottom of the Sea of Galilee. Taking into account the height of the sand and the rate of accumulation, researchers deduced that the monument is several thousand years old.
Looking deeper
Next, the researchers plan to organize a specialized underwater excavations team to learn more about the origins of the structure, including an investigation of the surface the structure was built on. A hunt for artefacts will help to more accurately date the monument and give clues as to its purpose and builders. And while it is sure to interest archaeologists, Prof. Marco says that the findings could also illuminate the geological history of the region.
"The base of the structure which was once on dry land is lower than any water level that we know of in the ancient Sea of Galilee. But this doesn't necessarily mean that water levels have been steadily rising," he says. Because the Sea of Galilee is a tectonically active region, the bottom of the lake, and therefore the structure, may have shifted over time. Further investigation is planned to increase the understanding of past tectonic movements, the accumulation of sediment, and the changing water levels throughout history.
###
American Friends of Tel Aviv University supports Israel's leading, most comprehensive and most sought-after center of higher learning. Independently ranked 94th among the world's top universities for the impact of its research, TAU's innovations and discoveries are cited more often by the global scientific community than all but 10 other universities.
Internationally recognized for the scope and groundbreaking nature of its research and scholarship, Tel Aviv University consistently produces work with profound implications for the future.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Mysterious monument found beneath the Sea of GalileePublic release date: 10-Jun-2013 [ | E-mail | Share ]
Contact: George Hunka ghunka@aftau.org 212-742-9070 American Friends of Tel Aviv University
Tel Aviv University research says unique structure is the product of skilled construction
The shores of the Sea of Galilee, located in the North of Israel, are home to a number of significant archaeological sites. Now researchers from Tel Aviv University have found an ancient structure deep beneath the waves as well.
Researchers stumbled upon a cone-shaped monument, approximately 230 feet in diameter, 39 feet high, and weighing an estimated 60,000 tons, while conducting a geophysical survey on the southern Sea of Galilee, reports Prof. Shmulik Marco of TAU's Department of Geophysics and Planetary Sciences. The team also included TAU Profs. Zvi Ben-Avraham and Moshe Reshef, and TAU alumni Dr. Gideon Tibor of the Oceanographic and Limnological Research Institute.
Initial findings indicate that the structure was built on dry land approximately 6,000 years ago, and later submerged under the water. Prof. Marco calls it an impressive feat, noting that the stones, which comprise the structure, were probably brought from more than a mile away and arranged according to a specific construction plan.
Dr. Yitzhak Paz of the Antiquities Authority and Ben-Gurion University says that the site, which was recently detailed in the International Journal of Nautical Archaeology, resembles early burial sites in Europe and was likely built in the early Bronze Age. He believes that there may be a connection to the nearby ancient city of Beit Yerah, the largest and most fortified city in the area.
Ancient structure revealed by sonar
The team of researchers initially set out to uncover the origins of alluvium pebbles found in this area of the Sea of Galilee, which they believe were deposited by the ancient Yavniel Creek, a precursor to the Jordan River south of the Sea of Galilee. While using sonar technology to survey the bottom of the lake, they observed a massive pile of stones in the midst of the otherwise smooth basin.
Curious about the unusual blip on their sonar, Prof. Marco went diving to learn more. A closer look revealed that the pile was not a random accumulation of stones, but a purposefully-built structure composed of three-foot-long volcanic stones called basalt. Because the closest deposit of the stone is more than a mile away, he believes that they were brought to the site specifically for this structure.
To estimate the age of the structure, researchers turned to the accumulation of sand around its base. Due to a natural build-up of sand throughout the years, the base is now six to ten feet below the bottom of the Sea of Galilee. Taking into account the height of the sand and the rate of accumulation, researchers deduced that the monument is several thousand years old.
Looking deeper
Next, the researchers plan to organize a specialized underwater excavations team to learn more about the origins of the structure, including an investigation of the surface the structure was built on. A hunt for artefacts will help to more accurately date the monument and give clues as to its purpose and builders. And while it is sure to interest archaeologists, Prof. Marco says that the findings could also illuminate the geological history of the region.
"The base of the structure which was once on dry land is lower than any water level that we know of in the ancient Sea of Galilee. But this doesn't necessarily mean that water levels have been steadily rising," he says. Because the Sea of Galilee is a tectonically active region, the bottom of the lake, and therefore the structure, may have shifted over time. Further investigation is planned to increase the understanding of past tectonic movements, the accumulation of sediment, and the changing water levels throughout history.
###
American Friends of Tel Aviv University supports Israel's leading, most comprehensive and most sought-after center of higher learning. Independently ranked 94th among the world's top universities for the impact of its research, TAU's innovations and discoveries are cited more often by the global scientific community than all but 10 other universities.
Internationally recognized for the scope and groundbreaking nature of its research and scholarship, Tel Aviv University consistently produces work with profound implications for the future.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Home ? business ? SCB plans to get into lending for commercial vehicles
SCB
Sucheera Pinijparakarn
The Nation June 10, 2013 1:00 am
Thanachart Bank and Krungsri Auto are the market leaders in auto lending.
Narong Srichukrin, first executive vice president and head of SCB's auto finance business division, said the bank was studying the commercial-vehicle market and expected to join the segment next year.
Lending for commercial-vehicle purchase is regarded as a high-yield business. Such vehicles are used in construction and subcontracting businesses, which will benefit from the government's infrastructure projects, while the borrowers' good liability is attracting lenders to secure this market.
SCB is also looking to get into motorcycle instalment loans, he said. The bank will not set up new subsidiaries to handle these new segments because it believes awareness of its brand and its large nationwide network will attract customers.
Narong noted that with the end of the government's first-car-buyer project, new auto loans were expected to shrink by 6 per cent to Bt800 billion from Bt860 billion last year. However, outstanding loans this year will be able to grow from the used-car market, forecast at Bt1.77 trillion, up from Bt1.5 trillion in 2012.
SCB estimates new loans this year at Bt120 billion, up from Bt100 billion last year, as it focuses more on used-car loans and strongly promotes its "My Car My Cash Prompt" product.
The bank plans to boost the proportion of used-car loans to 35 per cent by the end of this year from 30 per cent now.
Used-car loans and the new |cash-for-car products are expected to increase the car-loan portfolio from Bt180 billion year to date to Bt220 billion by year-end. Of the Bt180 billion, new-car loans account for Bt125 billion, Bt35 billion for used cars and the rest My Car My Cash.
He said the bank spent 12 months to develop MCMC Prompt to fill the gap between used-car loans and the My Car My Cash product.
The new product was designed for vehicle customers who prefer the convenience of withdrawing money when they want liquidity. Applicants can secure up to 80 per cent loan to value (LTV) to a maximum of Bt2 million at an interest rate of 18 per cent per annum. Interest will be charged only when the loan is drawn down. MCMC Prompt is suitable for business operators, Narong said.
SCB will offer ATM cards to the approved customers, and if they do not use the card for withdrawals, the bank will not charge interest. Vehicle age is limited to 10 years.
He said the bank expected half of MCMC Prompt customers would use the overdraft and this would help drive the portfolio of My |Car My Cash to Bt30 billion by year-end from Bt20 billion.
SCB is expanding the used-car customer base upcountry, especially in the Northeast. Lending upcountry this year is targeted to increase to 60 per cent from 55 per cent, he said.
Both used-car loans and My Car My Cash are high-yield products. The flat rate for a used-car loan is 3.5-4 per cent per annum for vehicles aged up to four years and 5-6 per cent for vehicles age seven to 10 years, higher than the 2.5-per-cent rate for a new-car loan.
Of 1.3 million new-car sales under the first-car scheme, 700,000 units were delivered last year and the remainder are being transferred to buyers this year. However, about 100,000 purchases are expected to be cancelled. The cancellations will not hurt the lenders as the buyers did not handle the financial transactions, but the dealers did.
Make your LabSpaces comments count. Start earning LabSpaces points by becoming a member! Learn more. 
![[ Back to EurekAlert! ]](https://lh3.googleusercontent.com/blogger_img_proxy/AEn0k_v4N9s8W9C1i2c9NVPAmvZjVmuVj9QMTJV0KxIPjngb0ZnbX5y91GLckS1nYiV5Z5FeZBWFvM100pMryjTYQBzIRGbTudlxKZZDKWDrJ_I=s0-d){kind=small}
Public release date: 10-Jun-2013
Share ]