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- 04/03/14--03:47: _Could Botox cure de...
- 04/03/14--06:28: _Using lasers and na...
- 04/03/14--07:56: _BIO-Europe 2014 | N...
- 04/03/14--14:39: _Genetically modifie...
- 04/03/14--18:27: _New opsins Chronos ...
- 04/04/14--00:23: _'Organ-on-a-chip' d...
- 04/04/14--20:14: _'Acid Bath' Stem Ce...
- 04/04/14--20:28: _STAP Stem cell work...
- 04/05/14--11:46: _Untangling motor ne...
- 04/06/14--05:26: _It’s official: scie...
- 04/08/14--01:10: _biotechology carree...
- 04/09/14--10:36: _Will I have the sam...
- 04/10/14--13:17: _Employer Reputation...
- 04/11/14--17:33: _Attract Endless Vis...
- 04/01/14--10:33: _Primer designing - ...
- 04/25/14--03:34: _Requirement of pneu...
- 04/26/14--07:36: _CRIPSR-Cas9 modific...
- 04/26/14--08:13: _First targeted drug...
- 04/26/14--08:33: _Roche — Nature Biot...
- 04/27/14--06:51: _Targeting the ‘supp...
- 04/03/14--03:47: Could Botox cure depression?
- 04/03/14--06:28: Using lasers and nanoballoons to battle cancer
- 04/03/14--07:56: BIO-Europe 2014 | November 3-5 2014 | Frankfurt, Germany
- 04/03/14--14:39: Genetically modified trees: easier paper and biofuel production
- 04/04/14--00:23: 'Organ-on-a-chip' device to mimic liver function
- 04/04/14--20:14: 'Acid Bath' Stem Cells May Have Been Made
- 04/04/14--20:28: STAP Stem cell work have have been repeated
- 04/06/14--05:26: It’s official: scientific research is economically worthwhile
- 04/08/14--01:10: biotechology carreer in usa
- 04/10/14--13:17: Employer Reputation - Does it impact my future prospects?
- 04/11/14--17:33: Attract Endless Visitors to Your Site With These 10 Simple Steps
- 04/01/14--10:33: Primer designing - What are universal primers?
- 04/25/14--03:34: Requirement of pneumococcal antigens- Pneumolysin & Autolysin
- 04/26/14--07:36: CRIPSR-Cas9 modification improves genome editing precision
- 04/26/14--08:13: First targeted drug for stomach cancer approved by FDA
- 04/26/14--08:33: Roche — Nature Biotechnology Symposium 2014
- 04/27/14--06:51: Targeting the ‘supply chain’ of tumour cells with DNA vaccine
A single injection of Onabotulinumtoxin A, better known as Botox, significantly reduces depressive symptoms in patients with major depression. This effect may be linked to the proposed association between facial expression and mood. These are the major findings of a new study to be published in the May 2014 edition of the Journal of Psychiatric Research.
In the largest study to consider the effect of Botox on depression, 74 subjects with DSM-IV major depression were randomly divided to receive a single injection of either Botox or placebo into the corrugator and procerus frown muscles in the forehead. The Montgomery–Asberg Depression Rating Scale (MADRS) was administered at the start of treatment and after three weeks and six weeks. The primary outcome measured in the study was ≥ 50% reduction in MADRS score. After six weeks, the results showed that there was a response rate of 52% in the Botox-treated group compared to only 15% in the placebo group; this was a significant difference. Also, in a secondary outcome measure of remission rate, assessed by a MADRS score of 10 or less, the results were 27% for the Botox-treated subjects as opposed to only 7% in the placebo group, again a significant difference. Overall, after six weeks the MADRS score in Botox-treated patients was reduced by on average 47% compared to 21% for those on placebo.
Author on the study, Dr Norman E. Rosenthal, MD, Clinical Professor of Psychiatry at Georgetown Medical School, commented, “This research is ground-breaking because it offers those who suffer from depression and their doctors an entirely new approach to treating the condition - one that doesn’t conflict with any other treatments.”
Co-author on the study, Dr. Eric Finzi, who first showed a link between inhibition of frowning by facial injection of Botox and reduction of depressive symptoms in a pilot study in 2006, explained: “This new research supports earlier facial feedback theory of Charles Darwin and William James which suggests that facial expressions influence mood.”
Finzi, E. and Rosenthal, N.E. (2014). Treatment of depression with onabotulinumtoxinA: A randomized, double-blind, placebo controlled trial. Journal of Psychiatric Research, Volume 52, Complete, Pages 1-6, May 2014. doi:10.1016/j.jpsychires.2013.11.006
Press release: Elsevier; available at http://www.elsevier.com/about/press-rele...with-botox [Accessed 3 April 2014].
Encapsulation of chemotherapeutic drugs in a ‘nanoballoon’ that can be activated by red laser to ‘pop’ and release its contents at the target site could improve efficiency of cancer treatment. The system is the subject of a new paper to be published on 3rd April in Nature Communications from researchers in the University of Buffalo, the University of Albany, Roswell Park Cancer Institute in Buffalo in the USA; and the University of Waterloo and McMaster University, both in Ontario, Canada.
While chemotherapeutic drugs are very effective against tumours, it can be a challenge to deliver them to the tumour site. They tend to interact along the way with healthy body tissues and blood, diluting their effectiveness and contributing to unpleasant side effects. In the current paper, the researchers encapsulated chemotherapeutic drugs in a modified liposome termed a ‘nanoballoon’ or ‘PoP liposome’. They consist of an organic compound called porphyrin and phospholipid. The nanoballoons are designed to protect the chemotherapeutic drugs from unwanted interactions along the way to the target site.
In in vivo experiments on mice, the researchers delivered the drug-laden nanoballoon intravenously and then hit them with red laser light at the target site, causing the nanoballoons to pop and release the drugs. The nanoballoons served a dual purpose in also sampling the tumour environment. This was achieved as once the laser was turned off, the nanoballoons closed up again, gathering in proteins and molecules from the environment. They could then be retrieved by drawing blood or taking a biopsy. This type of delivery and retrieval would be viable in human cancer patients.
Senior author on the paper, Dr Jonathan Lovell of the University of Buffalo explained: "Think of it this way…..The nanoballoon is a submarine. The drug is the cargo. We use a laser to open the submarine door which releases the drug. We close the door by turning the laser off. We then retrieve the submarine as it circulates through the bloodstream."
Studies are ongoing to determine why the treatment is so effective in tumour destruction in mice and in optimisation of the method. Dr Lovell says that human trials may be underway within five years.
Press release: University of Buffalo; available from http://www.eurekalert.org/pub_releases/2...040114.php [Accessed 3 April 2014].
20th Annual International Partnering Conference: BIO-Europe 2014
Organisers: EBD Group, the leading partnering firm for the global biotechnology industry, in alliance with the Biotechnology Industry Organization (BIO).
Dates: November 3rd –5th, 2014
Location: Portalhaus Messe Frankfurt, Germany
The website gives all the necessary information on conference agenda, hotel, exhibitions and other important facts.
About the conference:
The BIO Europe conference is the largest partnering conference serving the global biotechnology industry in Europe. Delegates are drawn from all aspects of the biotechnology industry to take the opportunity to enter into collaborations and partnerships. The conference will attract 3000 industry attendees from nearly 60 countries and more than 1800 companies. This offers an unprecedented opportunity for networking. Partnering is facilitated by EBD Group’s partneringONE® networking system which offers the chance to trawl a large pool of potential partners and then organise one-to-one meetings. The conference also features workshops, panels, presentations from companies and exhibitions. The preliminary programme will soon be available here: http://www.ebdgroup.com/bioeurope/program/index.php
Early registration deadline (reduced fee): 31st August 2014
Regular registration: after 31st August 2014
In Europe: Simon Englhart; EBD Group; +49 89 2388 756 0; firstname.lastname@example.org
In the USA: Nadia Manji; EBD Group; +1 760 930 0500; email@example.com
One of the main barriers to efficient processing of wood to give paper and biofuel is lignin, an aromatic polymer which makes up a large proportion of plant cell walls. Lignin contains ether bonds that are difficult to break, creating difficulties for biofuel and paper production as the lignin must currently be removed at considerable environmental and economic cost. However researchers at the University of British Columbia, the University of Wisconsin-Madison, Michigan State University, funded by Great Lakes Bioenergy Research Center, have made a breakthrough by genetically engineering poplar trees with modified lignin, containing more easily broken ester linkages. The study is published today in the journal Science.
In the study, the researchers isolated a gene for an enzyme called transferase which works by forming monolignol ferulate conjugates. These conjugates when used by the tree in lignin production results in introduction of the more easily broken ester linkages in the lignin. While previous studies had attempted to address the problem by reducing the quantity of lignin in trees by suppressing genes, this often resulted in stunted growth or susceptibility of the trees to weather conditions or pathogens. The strength of this study was that introduction of the transferase gene into the trees and consequent production of more easily broken down lignin left the strength and structure of the modified poplars intact. Dr Shawn Mansfield of the University of British Columbia, an author on the study, said: "It is truly a unique achievement to design trees for deconstruction while maintaining their growth potential and strength."
Removal of lignin from trees in production of biofuels and paper currently requires high energy expenditure and use of chemicals and results in production of environmental pollutants. These genetically modified poplars could be processed with less chemicals and energy. The new technique also means more effective recovery of lignin which can be used in other applications, for example adhesives, insolation, carbon fibres and paint additives.
The strategy adopted in this study would be transferable to other plants such as grasses, with potential to develop new biofuel sources as alternatives to petroleum. The authors acknowledge that genetic modification of plants is a controversial topic but point out that various strategies can be adopted to ensure that genes do not spread to the forest. These include growing crops away from native stands, introducing genes to make the trees or plants sterile and harvesting before reproductive maturity is reached. Eventually, they envisage the trees being planted like an agricultural crop rather than in native forests. Poplar in particular has potential as a biofuel crop as it grows rapidly and on marginal farmland.
Dr Mansfield concludes: "We're a petroleum reliant society… We rely on the same resource for everything from smartphones to gasoline. We need to diversify and take the pressure off of fossil fuels. Trees and plants have enormous potential to contribute carbon to our society."
Wilkerson, C.G., Mansfield, S.D., Lu,F., Withers, S., Park, J.-Y., Karlen, S. D., Gonzales-Vigil, E., Padmakshan, D., Unda, F., Rencoret, J. and Ralph, J. Monolignol Ferulate Transferase Introduces Chemically Labile Linkages into the Lignin Backbone. Science 4 April 2014: Vol. 344 no. 6179 pp. 90-93; DOI: 10.1126/science.1250161
Press release: University of British Colombia; available at http://www.eurekalert.org/pub_releases/2...040314.php [Accessed 3 April 2014].
"Optogenetics" allow researchers to stimulate synaptic activity in specific neurons that are made to express light-sensitive ion channels (channelrhodopsins). Despite the variety of opsins with different peak wavelength sensitivities, until now it has not been possible to independently activate two distinct neural populations without significant cross-talk or losing temporal resolution. Researchers at MIT reported in Nature on two new opsins with non-overlapping excitation spectra, Chronos and Chrimson, that allow independent optical excitation of distinct neural populations in mouse brain slices. These tools open the door to explore how multiple synaptic pathways interact to encode information in the brain.
Opsin genes occur naturally in microbial algae. In order to efficiently express these genes in mammalian cells, these researchers turned to GenScript for codon optimization and gene synthesis. GenScript has developed the leading codon-optimization algorithm:
OptimumGene?, patented in 2012 and continuously improved based upon the latest research findings.
Two new opsins with non-overlapping excitation spectra, Chronos and Chrimson, that allow independent optical excitation of distinct neural populations
The liver is a major cause of late-stage failure of new drugs due to toxicity reactions in humans that are not detected in animals. There is currently a lack of adequate in vitro liver tissue models that could be used to help overcome this limitation. However, a new study from researchers from the Center for Engineering in Medicine at the Massachusetts General Hospital has taken a step forward. The researchers used a novel ultrathin collagen matrix assembly which maintained liver cells in a fully functional and differentiated form. The study is published in the current issue of the journal Technology.
This microscale ‘organ-on-a-chip’ device is a prime example of 3-D microtissue biotechnological engineering. The use of collagen, a biologically relevant extracellular matrix molecule, allows liver cells to be provided with the correct extracellular matrix cues to maintain their morphology and This provides an in vitro tool for re-creating liver micro-tissues by layering together all the different liver cell types. This would facilitate study of healthy liver physiology and liver diseases. Importantly, new and experimental drug liver toxicity could be dissected before moving to animals or the clinic.
Senior author Dr Martin Yarmush explains: "This is a clever combination of the well-known layer-by-layer deposition technique for creating thin matrix assemblies and collagen functionalization chemistries that will really enable complex liver microtissue engineering by replicating the physiological cues that maintain the state of liver cell differentiation….The ultrathin collagen matrix biomaterial and its ability to keep liver cells functional for longer periods of time in chip devices will undoubtedly be a useful tool for creating liver microtissues that mimic the true physiology of the liver, including cell and matrix spatial geometries".
McCarty, W.J., Usta, O.B., Luitje, M., Sundhar Bale, S., Bhushan, A., Hegde, M., Golberg, I., Jindal, R. and Yarmush, M.L. (2014). A novel ultrathin collagen nanolayer assembly for 3-D microtissue engineering: Layer-by-layer collagen deposition for long-term stable microfluidic hepatocyte culture. Technology 02, 67 (2014). DOI: 10.1142/S2339547814500083.
Press release: World Scientific; available at http://www.worldscientific.com/page/pres...4-04-02-07 [Accessed 4 April 2014].
Accompanying figure: “An ultrathin collagen matrix assembly maintained the morphology and function of primary liver hepatocytes in a microfluidic organ-on-a-chip device for two weeks. Three images of the hepatocytes after two weeks in a microfluidic device: A phase contrast image of cell morphology at two weeks showing dense cytoplasm, distinct nuclei, and bright cell borders; bile canalicular network development (red); and cell nuclei (blue) and actin (green) organization demonstrating cell polarity.” Credit: William McCarty, the Center for Engineering in Medicine at the Massachusetts General Hospital, Harvard Medical School, and the Shriners Hospitals for Children-Boston).
2014-04-02-07.jpg (Size: 18.09 KB / Downloads: 2)
Scientist may have at last repeated the STAP "acid bath" stem cell experiments--except he created the stem cells without acid. Trituation worked for him. Will other scientists repeat his work in this controversial but potentially exciting area?
Just as Riken was delivering its sentence of fraud to the lead author on two controversial Riken/Harvard STAP stem cell papers, an unrelated scientist was creating--be thinks--STAP cells, if via a slightly different process. Scientists are working to repeat the work.
Defects in motor neurons lead to the devastating motor neuron diseases of which the most common human form is amyotrophic lateral sclerosis (ALS). A new study from scientists in the University of Wisconsin-Madison has identified a defect in production of the protein neurofilament-L (NF-L) as the cause of neurofilament tangles in the nerve fibres. These tangles interfere with transmission of signals to muscles, resulting in muscle paralysis. The study was published online on April 3 in the journal Cell Stem Cell.
In ALS, essential voluntary muscle activity such as speaking, walking, breathing, and swallowing is adversely affected. The disease causes paralysis and death. Motor neurons control muscles under normal circumstances, but in ALS, motor neurons lose the ability to relay signals from the brain to the muscles. It was recently discovered that a mutation in the Cu/Zn superoxide dismutase (SOD1) gene was present in some ALS patients.
Attempts by researchers to transfer the mutated gene to animals and identify drugs to treat those animals were not yielding useful results. The current study adopted a more fundamental approach by using induced pluripotent stem cells (iPSCs) from patients with the SOD1 mutation. This was achieved using skin cells from patients that were transformed into induced pluripotent stem cells and in turn, into motor neurons. These iPSCs can be used as "disease models," as they carry many of the same traits as their donor. Dr Su-Chun Zhang, senior author on the paper, explains that this approach had an advantage of the genetic approach which "can only study the results of a known disease-causing gene. With iPSC, you can take a cell from any patient, and grow up motor neurons that have ALS. That offers a new way to look at the basic disease pathology."
Using this approach, the research team identified neurofilament, a structure that transports chemicals and cellular subunits including neurotransmitters to the far reaches of the nerve cell, for example signalling the muscles to move. In particular, mutant SOD1 caused decreases in stability of the messenger RNA encoding NF-L and hence reduction in the proportion of NF-L in neurofilament. This in turn resulted ibn neurofilament aggregation and formation of tangles. These tangles block the nerve fibres, so that they malfunction and die.
This discovery may have far-reaching consequences beyond ALS. Dr Zhang explains: "Our discovery here is that the disease ALS is caused by misregulation of one step in the production of the neurofilament," but "very similar tangles" appear in Alzheimer's and Parkinson's diseases. "We got really excited at the idea that when you study ALS, you may be looking at the root of many neurodegenerative disorders."
The misregulation occurs very early in motor neuron development, making it the most likely cause of this disease. When the research team edited NF-L expression in the SOD1-mutant motor neurons, cells were returned to normal. Dr Zhang reports that scientists at the Small Molecule Screening and Synthesis Facility at UW-Madison are searching for ways to rescue the defective motor neurons by testing libraries of candidate drugs. He concludes: "This is exciting. We can put this into action right away. The basic research is now starting to pay off. With a disease like this, there is no time to waste."
Chen, H. et al. (2014) Modeling ALS with iPSCs Reveals that Mutant SOD1 Misregulates Neurofilament Balance in Motor Neurons. Cell Stem Cell, April 3rd; DOI: http://dx.doi.org/10.1016/j.stem.2014.02.004
Press release: University of Wisconsin-Madison; available at http://www.eurekalert.org/pub_releases/2...040114.php
A new study confirms that apart from the discovery of new knowledge and the long-term impact of such knowledge, scientific research also contributes to short-term economic gain. The study, published in this week’s Science journal, is the first of its kind to generate large-scale systematic data on short-term effects of science funding. The study was carried out by researchers from the American Institute of Research, the Committee on Institutional Cooperation, University of Michigan, University of Chicago, and the Ohio State University using data from the STAR METRICS project. This is a partnership between federal science agencies and research institutions set up to document the return to the public of science investments.
Policy-makers have an interest in the evidence of the short-term economic value of science-funding. The new study was carried out to document this in the United States. It focused on nine universities including Michigan, Wisconsin-Madison, Minnesota, Ohio State, Northwestern, Purdue, Michigan State, Chicago and Indiana. These universities were awarded approximately $7 billion in research and development funding in 2012 of which approximately 56% was from federal government. The study results shed light both on composition of the scientific workforce in these universities and the national impact of science research on businesses that supply laboratories funded by federal grants.
The study found that most people employed under federal research funding are not faculty members; in fact less than 20% are faculty researchers. The remainder is made up from graduate and undergraduate students, research staff, staff scientist and post-doctoral fellows. The researchers were also able to ascertain that each university receiving federal funding spent it in widely throughout the United States, with approximately 70% being spent outside their home states. While a large proportion of funding went to big companies, small enterprises also benefitted. In analysing the spending patterns, the researchers commented that "we were struck by how many are small, niche, high-technology companies…"
Co-author Roy Weiss, Deputy Provost for Research at the University of Chicago, said, "Research universities are dedicated to the discovery of new knowledge. This study reports the first cooperative endeavour by multiple universities to evaluate the benefit of government investment in research. In addition to making the world a better place by virtue of these discoveries, we now have data to support the overall benefits to society."
Julia Lane, Senior Managing Economist at the American Institutes for Research and a lead researcher on the project, further summarised, "This study provides evidence that while science is complicated, it is not magic. It is productive work. Scientific endeavours employ people. They use capital inputs. Related economic activity occurs immediately. Policy makers need to have an understanding of how science is produced when making resource allocation decisions, and this study provides that information in a reliable and current fashion."
Weinberg, B.A., Owen-Smith, J., Rosen, R.F., Schwarz, L., McFadden Allen, B., Weiss, R.E. and Lane, J. (2014). Science Funding and Short-Term Economic Activity. Science, 4 April 2014, 344(6179), 41-43; DOI: 10.1126/science.1250055
Press release: Committee on Institutional Cooperation; available from http://www.eurekalert.org/pub_releases/2...033114.php
please share your knoweledge regarding carrer prospects for those who have done m.sc biotechnology in India and wanna start carrer in usa . it can be ph.d or any job oriented course and then job in any biotechnology form in usa.
please guide.. what is the procedure, what is the eligibility crieteria, importat dates/ month for application , short term study so tht you can work there?
I would like to know if, with all things being equal, a Biotechnology degree is the same as a degree in Biology: Concentration in Biotechnology? Unfortunately, my university only offers this degree and I am stump on what to do with it once I graduate. I recently switch from Biochemistry to Bio: Conc. Biotech so I am completely clueless. I am worried about what career I can make out of this if I don't decide to go to a med or even a grad school. Thanks a lot!
Does the reputation of the Pharma/Biotech company that you work for matter when you apply for another position in the sciences or quality departments? Specifically, if you work for a company that doesn't have a great reputation, will that hurt your chances of getting hired elsewhere?
I have been offered a position (no other offers yet) and am wondering if, because I just graduated and this is my first industry position, working for a company with a not so stellar reputation will kill my chances of being hired at other companies in the years to come?
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Can anyone tell me about primer designing? Like how does one decide which part of the genome to consider for designing primer. And what if one doesn't know the genome like in case of designing primers for 16s rRNA of new organisms, how does one decide which part of the genome is 16s rRNA and how does he design primer? What are universal primers?
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The CRISPR-Cas9 nucleases are increasingly commonly used genome editing tools with potential for future therapeutic application. However, the monomeric versions up to use until now are prone to processing errors in which they produce unwanted off-target mutations at a significant rate, making it inappropriate for use in a clinical setting. A new study from researchers in Massachusetts General Hospital describes an important modification of this system what substantially improves the precision. The paper is published online in the journal Nature Biotechnology.
The CRISPR-Cas9 nucleases combine a short RNA segment that matches a relevant DNA target with Cas9, a DNA-cutting enzyme. They were initially developed in 2012 and are easier to use than earlier genome editing systems such as ZFN (zinc finger nuclease) and TALEN (transcription activator-like effector nuclease) systems. They have been used in animal models and human cells to induce genomic changes. However, previous reports from the laboratory where the current study was carried out had shown that CRISPR-Cas nucleases produced additional mutations in human cells at high frequency, even at sites differing from the intended DNA target by as many as five nucleotides.
In the current study, the targeting activity of Cas9 was fused to a nuclease called FokI. FokI only cuts when two guide RNAs are bound to the DNA within a strictly defined distance and orientation, a process known as dimerization. Thus the new nucleases were termed dimeric RNA-guided FokI nucleases (RFNs). The need for dimerization effectively doubled the length of DNA that must be recognized for cleavage by RFNs. This significantly improved precision of genome editing without any sacrifice of on-target modification effectiveness.
Senior author Dr J. Keith Joung explained the importance of this modification for future therapeutic applications that require high precision in genome editing: "This system combines the ease of use of the widely adopted CRISPR/Cas system with a dimerization-dependent nuclease activity that confers higher specificity of action…..Higher specificity will be essential for any future clinical use of these nucleases, and the new class of proteins we describe could provide an important option for therapeutic genome editing." The researchers have also developed a software application that will help users identify potential RFN target sites. They have incorporated it into the freely available software package ZiFiT Targeter, which can be accessed at http://zifit.partners.org.
Tsai, S.Q., Wyvekens, N., Khayter, C., Foden, J.A., Thapar, V., Reyon, D., Goodwin, M.J., Aryee, M.J. and Joung, J.K. Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nature Biotechnology (2014); doi:10.1038/nbt.2908
Press release: Massachusetts General Hospital; available at http://www.eurekalert.org/pub_releases/2...042514.php
A new drug targeting angiogenesis- new blood vessel growth- of tumours has just received approval from the U.S. Food and Drug Administration (FDA) as a second line treatment for stomach cancer after initial chemotherapy has been unsuccessful. The generic name for the drug is ramucirumab. It is a monoclonal antibody directed against the vascular endothelial growth factor (VEGF) receptor-2 on blood vessel cells. It has been approved based on the results of a clinical trial carried out by scientists in Dana-Farber Cancer Institute and the approval was announced by the manufacturers, Lilly Oncology, of Indianapolis. It will be sold under the name Cyramza.
Advanced stomach cancer is notoriously difficult to treat effectively. In 2014 an estimated 22,290 people will be diagnosed with stomach cancer in 2014; 10,990 of them will die of the disease. This is the first FDA-approved treatment for this form of cancer.
The clinical trial on which the approval was based was called REGARD and was led by Dr Charles Fuchs, director of the Gastrointestinal Cancer Center at Dana-Farber. The patients enrolled in the study had advanced or metastatic gastric cancer – cancer of the stomach – or cancer at the junction of the oesophagus with the upper part of the stomach. Their cancer had progressed in spite of initial chemotherapy treatment.
The results of the trial showed that use of ramucirumab induced improvement in survival and a reduced rate of cancer progression compared to placebo. The median overall survival of patients with advanced stomach was increased modestly by 37%, to 5.2 months compared to 3.8 months for patients on placebo. They also had a 62% increase in survival time before the cancer progressed, at 2.1 months compared to 1.3 months for placebo. The modest nature of the improvements has led some commentators to question whether ramucirumab effects are really meaningful or just marginal. Dr Fuchs explains: "The benefit is modest, but it's clearly better than what we were previously doing…. when you chip away and develop drugs in sequence, ultimately you do have meaningful clinical improvements."
Another randomised clinical trial on ramucirumab, called the RAINBOW trial, examined use of ramucirumab in combination with paclitaxel in patients with advanced stomach or gastroesophageal junction cancer. The combination prolonged overall survival from a median of 7.36 months to 9.63 months. The current FDA approval of ramucirumab does not extend to combination therapy, but Lilly Oncology plans to submit the RAINBOW data in order to seek expanded approval. These results have increased confidence that the effects of ramucirumab may be more than marginal.
Dr Fuchs concludes: "For years we have looked for new and really effective drugs for stomach cancer….We have relied on standard chemotherapies for a long time, and we've needed targeted agents based on the fundamental biology of stomach cancer."
Press release: Dana-Farber Cancer Institute; available from http://www.eurekalert.org/pub_releases/2...042114.php
Wadhwa, R., Elimova, E., Shiozaki, H., Sudo, K., Blum, M.A., Estrella, J.S., Chen, Q., Song, S. & Ajani, J.A. 2014, "Anti-angiogenic agent ramucirumab: meaningful or marginal?", Expert Review of Anticancer Therapy, vol. 14, no. 4, pp. 367-379.
Shah, M.A. 2014, "Gastrointestinal cancer: targeted therapies in gastric cancer-the dawn of a new era", Nature Reviews.Clinical oncology, vol. 11, no. 1, pp. 10-11.
If you are keenly interested in the domain of Membrane Transport and Different drug-delivery systems, then Roche's "Nature Biotechnology Symposium 2014: Unlocking Cell Transport Barriers to Deliver Large Molecule Therapeutics". is a must attend!
The symposium is aimed at bringing together the scientific community (especially the cell-biologists and drug-delivery experts) to understand the intricacies and developments in membrane biology that may be exploited to efficate the current drug distribution, cellular uptake and delivery systems.
Importantly: It's a FREE event.
( attendees will be selected to participate on the basis of their application for admission)
Application and abstract submission deadine: June 16, 2014
Venue: Roche Forum Buonas, Buonas, Switzerland
September 3-5, 2014
A novel DNA vaccine that targets the vasculature (blood vessels) that keep tumours supplied with blood has shown promising results in mouse tumour models. The study, from researchers in the University of Pennsylvania in the USA and the University of Perugia in Italy, is published in the Journal of Clinical Investigation.
Angiogenesis is the name for the process of growth of new blood vessels from pre-existing vessels. It is an essential process in normal processes such as pregnancy, embryonic development, and wound healing. Tumour angiogenesis is a promising target for cancer therapy but previous strategies have encountered problems of specificity as processes such as wound healing were also affected. The current study identified a protein called tumour endothelial marker 1 (TEM1) as a promising target as it is overexpressed in the vasculature many tumours in both humans and mice but is expressed at low or undetectable levels in normal tissues. TEM1 is implicated in tumour vascular cell adhesion, migration and development as well as tumour progression. Its overexpression is linked to poor survival.
In the current study, the research team designed a vaccine in which Tem1 cDNA (which encodes TEM1 protein) was fused to a fragment of tetanus toxin (TT) as adjuvant in a DNA vehicle called a plasmid. This generated the Tem1-TT vaccine. The researchers tested Tem1-TT vaccine by both prophylactic and therapeutic vaccine approaches in mouse models of cancer.
In the prophylactic approach, mice were first inoculated with Tem1-TT vaccine three times at weekly intervals before being subjected to tumour challenge. The results showed that there was significant tumour protection when compared with plasmid carrying only single Tem1 or TT separately. In the therapeutic approach, the mice were first subjected to tumour challenge and then were given 3 weekly vaccinations after 3-5 days. In this case, the vascularity, or blood vessel growth, of tumours was reduced, there was increased infiltration of anti-tumour CD3+ T cells into the tumour and progression of established tumours was controlled. Importantly, the researchers established that effective Tem1-TT vaccination did not affect normal processes such as wound healing and reproduction.
In a bonus anti-tumour effect, the researchers showed that after killing the endothelial cells of the tumour vasculature, a process called epitope spreading resulted. Killing of the endothelial cells created a rich source of dead or dying tumour cells capable of inducing a cross-priming event from mouse immune cells against tumour antigens other than TEM. This process increased the therapeutic efficacy of the vaccine.
Senior author Dr Andrea Facciabene explains how this study potentially advances the field of cancer vaccines: "Until now there have been a lot of clinical trials using DNA vaccines to target tumours themselves, but unfortunately the results have been disappointing…This is a different approach which should heighten optimism for cancer vaccines in general. Moreover, based on what we’ve seen in our mouse studies, this vaccine doesn’t seem to show any significant side effects."
The authors are hopeful that targeting TEM1 will have efficacy as both a prophylactic defence against cancer and to complement therapies such as radiotherapy and chemotherapy. Dr Facciabene explains "Using this vaccine simultaneously with radiation may eventually have a double synergy…Both treatments affect the tumor endothelium, radiotherapy could help the phenomenon of epitope spreading induced by the TEM1-TT vaccine."
Future plans are to continue pre-clinical work with human TEM1 and to move on to Phase I human clinical trials.
Facciponte, J.G., Ugel, S., De Sanctis, F., Li, C., Wang, L., Nair, G., Sehgal, S., Raj, A., Matthaiou, E., Coukos, G. and Facciabene, A. Tumor endothelial marker 1–specific DNA vaccination targets tumor vasculature. J. Clin. Invest. 2014; 124(4):1497–1511 doi:10.1172/JCI67382
Press release: University of Pennsylvania School of Medicine; available at http://www.uphs.upenn.edu/news/News_Rele...acciabene/