Industrial Technologies 2014 | April 9-11 2014 | Athens, Greece

November 24, 2013, 4:30 pm

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Industrial Technologies 2014 Conference - Smart Growth through Research and Innovation – towards Europe 2020

Joint Organisers: FORTH/ICE-HT, Spinverse Ltd., SEV Hellenic Federation of Enterprises, The Laboratory for Manufacturing Systems & Automation (LMS) at the University of Patras, SYROS’ Shipbuilding and Industrial Enterprises S.A., Frigoglass, CNR-ITIA, The Chamber of Achaia, ATHENA RIC; supported by The European Commission Directorate for Research and Innovation

Dates: April 9th-11th, 2014

Location: Athens International Conference Centre, Megaron, Athens, Greece.

Website: http://www.industrialtechnologies2014.eu/
The website gives all the necessary information on abstract submission, fees, registration, conference agenda, hotel, exhibitions and other important facts.

Conference theme
"Smart Growth through Research and Innovation – towards Europe 2020"
The modern and ancient worlds will meet as the Greek Presidency of the European Council underpins the Industrial Technologies 2014 conference to be held in Athens, Greece. Funding has been made from the European Union Seventh Framework Programme.

Purpose of the conference
The Industrial Technologies 2014 conference aims to integrate nano-, bio-, materials- and production- technologies. It offers opportunities to develop collaborations between research and industry and showcases cutting-edge research and innovations as well as giving rising companies from all around Europe an opportunity to raise their profile.
The event takes place during the Greek Presidency of the European Council and has received funding from European Union Seventh Framework Programme.

Topics:
The main topics include:
•European and global developments in the high-tech arena,
•Re-industrialisation and regional development in Europe,
•Technological and entrepreneurial opportunities especially for the Balkan and Mediterranean states, and
•Opportunities in Horizon 2020 in the field of enabling technologies

Plenary Sessions
• PLENARY 1: Re-industrialisation and smart growth through research and innovation in Europe
• PLENARY 2: New technologies impacting everyday life
• PLENARY 3: Improving Europe’s competitiveness through regional development
• PLENARY 4: Horizon 2020, NMP and Regional Funds Research Strategies

Parallel Sessions
1: Innovating products for regional growth in Europe: Co-evolution of products, processes and systems
2: Low-carbon energy enabling sustainable production and technology leadership across Europe
3: Fostering EU competence and competitiveness through innovation and smart specialisation
4: Producing better with less – resource-efficient factories
5: Biotechnology as driver for sustainability and new industries
6: From a research idea to a finished product – experiences from large companies and SMEs in the value chain
7: Advanced processes for efficient, high quality and agile manufacturing
8: Sustainable healthcare made possible with advanced materials and nanotechnologies
9: Ensuring availability and security of water and food supplies – New business opportunities for European industry
10: Nanotechnology advances and how nano-enabled products change our world and daily life
11: Integration of industrial and materials research communities along the value chains: the innovation way to future sustainable products
12: Competence-building, education and skills for industrial competitiveness
13: Innovative technologies for energy efficient buildings
14: Advanced technologies for cleaner transport – lightweight and low emission
15: Innovation and up-scaling: From clusters to demonstrators and pilot lines
16: Safety of advanced materials and processes
17: The smart manufacturing systems of the future: flexible, adaptive and safe

Confirmed Plenary Speakers
•Sheila Hamilton, Technical Director of Teknek
•Adrian Harris, Director General of Orgalime
•Stefan Rinck, CEO of Singulus Technologies

Important dates
Workshop application: before 30th November 2013
Best Project Award application before 12th January 2014
Poster Session and Best Poster Award applications before 12th January 2014
Participation in the FutureFlash! demo competition exhibits showcasing applications before 31st December 2013
Smartest Region in Europe award applications before 31st December 2013

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Nexavar to Treat Differentiated Thyroid Cancer on FDA’s Approval

November 24, 2013, 11:50 pm

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The prevailing drug Nexavar is once again approved by FDA on 22nd November 2013 to treat yet another type of cancer, the metastatic Thyroid cancer (highly differentiated). This is the third approval bagged by the drug Nexavar a product of Bayer and Onyx Pharma in addition to the earlier approval of the drug in 2005 to treat highly developed renal cell carcinoma (Kidney cancer) and approval in 2007 to treat hepatocellular carcinoma (liver cancer). Nexavar is also designated as the orphan product by FDA.

Thyroid cancer is a condition of malignancy in thyroid gland. It is classified into different types like papillary, follicular, medullary, poorly differentiated and anaplastic thyroid cancer among which the papillary and follicular thyroid cancer are the two types categorized under differentiated thyroid cancer. Papillary thyroid cancer constitutes about 75% to 85% of thyroid cancer cases and follicular thyroid cancer amounts up to 10% to 20% of thyroid cancer cases. A study by American cancer society states that in the current year about 1040 females and 810 male will succumb to thyroid cancer. Surgical removal of thyroid gland, radioactive iodine therapy and chemotherapy are the considered options carried out to better the lives of the thyroid cancer patients and Nexavar is an assurance to thyroid cancer patients who does not respond to any of these conventional treatment methods.

The effectiveness of the drug Nexavar is acknowledged through the findings from the clinical study. Treatment with Nexavar is found to prolong the survival period (with no cancer progression) of the affected persons to about 41 percent compared to the patient category treated with placebo. The study was conducted on patients with metastatic (differentiated) thyroid cancer and patients with the history of recurrence of thyroid cancer at the local site who did not respond to the existing treatment methods.

Nexavar also called as Sorafenib gains control over the growth of the cancer cells by functioning as a protein inhibitor. Some of the side effects should the patient using Nexavar therapy be aware are restricted blood flow, bleeding, skin disease, hair loss, fluctuating Thyroid hormone level, liver inflammation, fatigue and diarrhea. Patients are advised to be transparent to the doctors about all the other medications taken by them before starting Nexavar therapy and also should discuss about any allergies they are prone to. Nexavar taken by pregnant women poses devastating effect on the fetus and it is advisable for female patients not to try to conceive while taking Nexavar.

Thus Nexavar occupies a prominent place in the list of treatment methods available to treat kidney, Liver and Thyroid cancer.

Reference
http://www.fda.gov/NewsEvents/Newsroom/P...376443.htm
http://in.reuters.com/article/2013/11/22...4F20131122
http://www.nexavar-us.com/scripts/pages/.../index.php
http://en.wikipedia.org/wiki/Thyroid_cancer
http://www.uptodate.com/contents/differe...management
http://www.rxlist.com/nexavar-drug.htm

Hepatitis C drug Simeprevir wins FDA approval

November 25, 2013, 11:26 am

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Previously on this forum we reported that a group of experts had recommended FDA approval of the Johnson and Johnson experimental Hepatitis C drug simeprevir (http://www.biotechnologyforums.com/thread-2564.html). At that time we noted that while the FDA is not obliged to follow the group’s recommendations, in practice it often does. We can confirm that last Friday the FDA gave approval to Johnson and Johnson and its partner Medivir to market simeprevir, which will be sold under the name of Olysio.

Simeprevir is a second generation protease inhibitor which has been developed as part of the research community’s response to the need to develop Hepatitis C drugs that have reduced or no need for co-treatment with interferon. While simeprevir still requires co-administration of PEGylated interferon and ribavirin, it is in reduced amounts compared to the current protease inhibitors on the market, i.e. Incivek (Vertex) and Victrelis (Merck). Phase III trial data suggests that simeprevir may be particularly beneficial in patients who have not responded positively to previous treatment. It is also easily administered as a simple daily pill and is safe and well-tolerated while delivering a sustained virological response.

However, research efforts in this field are intense and simeprevir may find itself in competition relatively soon with drugs such as Enanta’s lead protease inhibitor ABT-450 which recently delivered positive phase III data in difficult-to-treat Hepatitis C patients in a pegylated interferon-free regimen, as we recently reported (http://www.biotechnologyforums.com/thread-2637.html). The intensity of the work in this field can only be of benefit to Hepatitis C patients.

Sources

http://www.fiercebiotech.com/story/jj-me...2013-11-25 [Accessed 25 November 2013].

http://www.fiercebiotech.com/press-relea...is-c-virus [Accessed 25 November 2013].

http://www.biospace.com/News/abbvie-enan...s-c/316030 [Accessed 19 November 2013].

FLISIAK, R., JAROSZEWICZ, J. and PARFIENIUK-KOWERDA, A., 2013. Emerging treatments for hepatitis C. Expert Opinion On Emerging Drugs, 2013

HAYASHI, N. et al., 2013. Once-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naïve hepatitis C genotype 1-infected patients in Japan: the DRAGON study. Journal of gastroenterology, 2013

YOU, D.M. and POCKROS, P.J., 2013. Simeprevir for the treatment of chronic hepatitis C. Expert opinion on pharmacotherapy 2013

http://www.wboc.com/story/23782859/fda-a...tis-c-drug

Euro-Mediterranean Conference on Natural Products | January 4-6 2014 | Cairo, Egypt

November 25, 2013, 12:07 pm

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3rd Euro-Mediterranean Conference on Natural Products: From BioTechnology to NanoMedicine

Organisers: BioNaters

Dates: January 4th-6th, 2014

Location: Conference Hall, The National Research Center, Dokki, Cairo, Egypt.

Website: http://www.bionats.org/
The website gives all the necessary information on abstract submission, fees, registration, conference agenda, hotel, exhibitions and other important facts.

Purpose of the conference
The purpose is to promote discussion and interaction among academics, researchers and professionals in the field of natural products, including metabolic networks, vitamins, carotenoids, flavonoids, anti-nutrients, toxins, products of plant-associated microorganisms and bioactive proteins. The conference will include herbal medicine, plant-derived drugs, phytopharmaceuticals, synthetic drugs, ethno-pharmacology, biodiversity and legislations and research strategies

Topics:
• Production, Purification, Stability and Efficacy of Natural Products.
• Isolation, Structure Elucidation, Biosynthesis and Informatics.
• Biotechnology and Molecular Biology.
• Antimicrobial Spectrum and Mode of Action of Natural Products.
• Pharmacogenomics, Pharmacodynamics and Pharmacokinetics.
• Nanoformulations, Nanoparticle Delivery and Nanotoxicology.
• Pharmacology, Toxicology and Biological Actions.
• Food Additives, Supplements, Flavours, and Health Promoters.
• Risk Assessment, Formulations, Applications & Standardizations.

Confirmed Speakers
• Prof. Bharat B Aggarwal, Department of Experimental Therapeutics, University of Texas, USA
• Prof. Amal Kasry, AIT Austrian Institute of Technology, Austria.
• Prof. Ashraf Abadi, German University in Cairo, Egypt
• Prof. Abdel-Fattah Badr, Helwan University, Cairo, Egypt
• Prof. Ezzat Awad, Medical University of Vienna, Vienna, Austria
• Prof. Hanaa Ali Hassan, Faculty of Science, Mansoura University.
• Dr. Hassan Sher, University of Swat, Pakistan.
• Prof. Loretta Gratani, University of Rome, Sapienza, Italy.
• Prof. Johannes Breuss, Medical University of Vienna, Vienna, Austria.
• Prof. Jamilah Bakar, Institute of Halal Products Research (IPPH), Universiti Putra Malaysia
• Dr. Mohamed F. R. Hassanien, Zagazig University, Egypt.
• Prof. Mona Hetta, Beni-Suef University
• Prof. Nuriye Akev, Istanbul University, Turkey
• Prof. Phoency Lai, National Taiwan University
• Prof. Safaa Al- Hamdani, Jacksonville State University, Jacksonville, USA

Nitric oxide synthase inhibitors enhance antibiotic-mediated bacterial killing

November 26, 2013, 9:16 am

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Nitric oxide synthase (NOS) inhibitor compounds, originally developed as experimental drugs for neurodegenerative disorders, may have unexpected extra applications in assisting antibiotics in the fight against drug-resistant bacteria. As we have pointed out on this forum previously, antibiotic resistance is a major public health issue and has prompted intense research efforts to attempt to understand and address it (http://www.biotechnologyforums.com/thread-2535.html; http://www.biotechnologyforums.com/thread-2540.html).

In a major study published in PNAS this week, researchers from Northwestern University in the USA used neuronal NOS (nNOS) inhibitors, known as leads compounds 1 and 2, in an attempt to boost the activity of antibiotics against Bacillus subtilis (which is a non-pathogenic strain with strong similarities to Staphylococcus aureus) and Bacillus anthracis. The strategy was suggested by a study in S. aureus, one of the few bacterial species that express bacterial NOS (bNOS). That study showed that in a bNOS mutant of the epidemic community-acquired methicillin-resistant S. aureus (MRSA) USA300 clone, the MRSA became more susceptible to killing both by immune cells such as neutrophils, by reactive oxygen species and by cell envelope-specific antibiotics including vancomycin and daptomycin. In the PNAS study, two nNOS inhibitors impeded B. subtilis growth under oxidative stress and promoted more efficient killing of B. subtilis and Bacillus anthracis by antibiotics than the antibiotic by itself. Crystal structures showed that the two compounds bind differently to the bacteria.

These studies raise hopes that nNOS inhibitors may be a lead in the fight against drug resistance in pathogens containing bNOS, such as S. aureus, as well as battling neurodegenerative disorders in which NO is overproduced by nNOS.

Sources
HOLDEN, J.K., LI, H., JING, Q., KANG, S., RICHO, J., SILVERMAN, R.B. and POULOS, T.L., 2013. Structural and biological studies on bacterial nitric oxide synthase inhibitors. Proceedings of the National Academy of Sciences, 110 (45): 18127 DOI: 10.1073/pnas.1314080110

JING, Q., LI, H., FANG, J., ROMAN, L.J., MARTáSEK, P., POULOS, T.L. and SILVERMAN, R.B., 2013. In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures. Bioorganic & medicinal chemistry, 21(17), pp. 5323-5331.

VAN SORGE, N.M., BEASLEY, F.C., GUSAROV, I., GONZALEZ, D.J., VON KÃCKRITZ-BLICKWEDE, M., ANIK, S., BORKOWSKI, A.W., DORRESTEIN, P.C., NUDLER, E. and NIZET, V., 2013. Methicillin-resistant Staphylococcus aureus bacterial nitric-oxide synthase affects antibiotic sensitivity and skin abscess development. The Journal of Biological Chemistry, 288(9), pp. 6417-6426.

MM-121 fails primary end-point in Phase II breast cancer trial

November 26, 2013, 1:32 pm

≫ Next: FDA Approves the First Adjuvant Based H5N1 Bird Flu Vaccine

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Merrimack Pharmaceuticals and Sanofi have announced that its drug MM-121, an ErbB3 antibody, did not meet the primary endpoint in a Phase II trial on women with ER/PR+, HER2- breast cancer. This follows on from a previous failure to meet the primary endpoint in a phase II trial on ovarian cancer patients, which we referred to previously on this forum (http://www.biotechnologyforums.com/thread-2581.html). However, Merrimack remains firmly optimistic that the biomarker results of these studies confirms that a sub-population of ER/PR+, HER2- breast cancer patients with biomarkers mechanistically linked to ErbB3 signalling may benefit from the drug. The company confirmed that these are the same ErbB3-signalling-linked biomarkers that were indicated in the ovarian cancer Phase II trial. ErbB3 (HER3) is a member of the epidermal growth factor receptor (ErbB; EGFR) family.

The most recent phase II trial was carried out to determine the effect of adding MM-121 to exemestane compared to exemestane in the absence of MM-121. The trial, on 118 patients who had previously failed anti-oestrogen therapy, was double-blinded, randomised and placebo-controlled and the primary endpoint was progression-free survival (PFS). Although the trend was in favour of the MM-121-containing treatment, the primary end-point was not met. However, similarly to the ovarian cancer trial, a sub-population comprising approximately one third of the 55 biomarker-evaluable patients was identified. The undisclosed markers, linked to ErbB3 signalling, were confirmed to be the same as those identified in the ovarian cancer trial in which MM-121 was evaluated in conjunction with paclitaxel. Gavin MacBeath, the co-founder and Vice-President of translational research at Merrimack, maintained that the data ‘serves to further confirm our original biomarker hypothesis’ and that ‘These data further implicate ErbB3 signalling as a general mechanism of resistance to standard-of-care therapies.’ Safety data indicated that adverse events data was similar between the control and treatment arms and no increase in serious adverse events were reported in the treatment arm.

In a second phase II trial, MM-121 was tested in combination with paclitaxel on 99 patients. Pathologic complete response (pCR) rate, which is based on measurement of absence of invasive cancer in breast and lymph node tissue after neoadjuvant therapy and is accepted to be a strong indicator for prolonged disease-free survival, was measured although no primary endpoint was set. pCR was found to be 10.8% in the presence of MM-121 as opposed to 3.3% in its absence. Translational analysis is on-going.

Merrimack and Sanofi will continue to pursue their biomarker theory.

Sources

http://www.fiercebiotech.com/press-relea...hase-2-e-0 [Accessed 26 November 2013].

SCHOEBERL, B. et al., 2010. An ErbB3 antibody, MM-121, is active in cancers with ligand-dependent activation. Cancer research, 70(6), pp. 2485-2494

http://www.fiercebiotech.com/press-relea...-sar256212 [Accessed 30 October 2013].

FDA Approves the First Adjuvant Based H5N1 Bird Flu Vaccine

November 26, 2013, 11:19 pm

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Pandemrix, the first adjuvant based vaccine is approved by FDA to be used against the H5N1 Bird flu viral infection. The vaccine developed by GlaxoSmithKline’s subunit ID Biomedical is decided to be kept in the control of the United States department of Health and Human Services by including it in the list of National stock pile. Therefore Pandemrix vaccine cannot be commercialized.

H5N1 viral strain, the reason behind the bird flu is a subclass of Influenza A virus. It is a RNA virus and the H5N1 coding represents the type of the viral strain where H stands for the Hemagglutinin portion of the virus which influences the bonding between the virus and the target cell and N stands for the Neuraminidase enzyme which aids the release of the replicated viruses from the infected cell. H5N1 categorized as the High Pathogenic Avian Influenza Virus is highly potential to develop a pandemic among human population when transmitted from human to human. The mortality rates of H5N1 infection is identified to be relatively higher than the H1N1 (swine flu) infection.

Pandemrix gains the status of the first adjuvant vaccine following its approval by FDA against H5N1 bird flu. Adjuvants are the components that prove to enhance the response of the immune system towards the antigenic particles and also considered to be effective on mutant strains of the virus. The efficiency of the Pandemrix vaccine against the bird flu is found to be high along with the adjuvant combination. Earlier the adjuvant based vaccine against H1N1 (swine flu) was rejected by FDA as the Vaccine without the adjuvant was found to be more efficient. There are also reported cases of Narcolepsy recorded in patients who received adjuvant based vaccination.

However the lethality of the H5N1 bird flu, its threat to the global population as a pandemic and the recommendation of the Pandemrix vaccine by the advisory panel to the FDA are the key factors supporting the approval of the vaccine by FDA. Also the adjuvant based vaccine Pandemrix renamed as Pumarix gained the approval by the European regulators. In case of an outbreak of H5N1 the vaccine will be distributed by the Health department of the state to protect the people.

Reference
http://www.reuters.com/article/2013/11/2...XD20131122
http://www.ctvnews.ca/health/fda-approve...z2lTgtr6ZA
http://www.nbcnews.com/health/fda-approv...2D11641784
http://en.wikipedia.org/wiki/Influenza_A...btype_H5N1
http://en.wikipedia.org/wiki/Pandemrix

EMBL Microfludics Conference | July 23rd to 25th 2014 | Heidelberg

November 15, 2013, 5:20 am

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EMBL Conference: Microfluidics 2014

Organisers: European Molecular Biology Laboratory (EMBL):
Scientific Organisers: Christoph Merten, EMBL Heidelberg, Germany; Stephen Quake, Department of Bioengineering, James H. Clark Center, Stanford University, USA;
Conference Organiser: Gwen Sanderson, EMBL Heidelberg, Germany

Dates: July 23rd to 25th 2014

Location: EMBL Heidelberg, Germany

Website: http://www.embl.de/training/events/2014/...index.html
The website gives all the necessary information on abstract submission, fees, registration, conference agenda, hotel, exhibitions and other important facts.

Purpose of the conference
Microfluidics stands at the interface of physics, engineering, chemistry and biology and uses a variety of applications relevant to biotechnology. These include (but are not limited to) chemical synthesis, nucleotide sequencing, functional genomics and single molecule/ single cell/ single organism studies. Many of these applications, including next-generation sequencing devices, have been revolutionised by miniaturisation, paving the way for global gene analysis and hence transforming biology.
The EMBL Microfluidics Conference 2014 aims to bring together top researchers in the field and to spark scientific exchange, also across different disciplines. The latest Lab-on-a-Chip technologies and applications will be presented.

Confirmed Speakers:
• Helene Andersson Svahn, Science for Life Laboratory, Sweden
• Andrew deMello, ETH Zurich, Switzerland
• Petra Dittrich, Laboratorium für Organische Chemie, ETH Zurich, Switzerland
• Albert Folch, University of Washington, USA
• Carl Hansen, University of British Columbia, Canada
• Amy E. Herr, UC Berkeley, USA
• Andreas Manz, Universität des Saarlandes, Germany
• Christoph Merten, European Molecular Biology Laboratory, Germany
• Steve Quake, Stanford University, USA
• Vincent Studer, CNRS, France
• Patrick Tabeling, ESPCI Paris, France
• Savas Tay, ETH Zurich, Switzerland
• Jean-Louis Viovy, CNRS, France
• Dave Weitz, Harvard University, USA
• Aaron Wheeler, University of Toronto, Canada
• Roland Zengerle, University of Freiburg, Germany

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Pros and Cons of Biological degradation - Need Help !!

December 2, 2013, 9:22 am

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Can someone tell me something about good and bad sides of Biological degradation. I need that information for my seminar on biotechnology. Thanks in advance.

Hepatitis C drug sofosbuvir: FDA approval imminent but legal challenges loom

December 3, 2013, 5:56 am

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Recently on this forum, we have been following the intense on-going research efforts among pharmaceutical companies to address the problem of interferon-based treatments for hepatitis C patients. Problems encountered with interferon-containing medications include contraindications such as psychiatric problems and also a high burden of adverse events. Johnson and Johnson’s drug simeprevir, a second-generation protease inhibitor, is one example of a drug developed to address this issue. Recently winning FDA approval to be marketed under the name of Olysio (http://www.biotechnologyforums.com/thread-2661.html), it reduces the amounts of PEGylated interferon and ribavirin that have to be co-administered. Another drug, Enanta’s lead protease inhibitor ABT-450, has recently delivered promising Phase III data in difficult-to-treat Hepatitis C patients in a pegylated interferon-free regimen (http://www.biotechnologyforums.com/thread-2637.html).

Now entering into the arena is a different type of drug, the pyrimidine nucleotide analog inhibitor of the hepatitis C virus NS5B polymerase, sofosbuvir. This drug, developed by the company Gilead, recently won the backing of FDA agency experts and is expected to be approved by the FDA on December 8th. The drug has shown high efficacy and good tolerability in various treatment combinations in clinical trials and offers the potential to either reduce or remove interferon from the treatment regime. However, it may not all be uncomplicated in bringing this drug to the market as Gilead are facing a legal challenge alleging patent infringements from Idenix Pharmaceuticals, as well as being embroiled in legal issues with Merck, who also claim patent infringements and Roche, who are claiming the licence on sofosbuvir based on a partnership Roche had with Pharmasset, the company which was bought outright by Gilead in order to gain the rights to sofosbuvir. With projected annual sales of approximately $5 billion a year, Gilead will be vigorously defending its exclusive rights to sofosbuvir. As we have previously surmised, the growing ranks of Hepatitis C drugs which reduce or dispense with the need for interferon can only be of benefit for patients, whatever the internal wrangling between pharmaceutical companies.

Sources

http://www.fiercebiotech.com/story/ideni...2013-12-02 [Accessed 3 December]

GANE, E.J., STEDMAN, C.A., HYLAND, R.H., DING, X., SVAROVSKAIA, E., SUBRAMANIAN, G.M., SYMONDS, W.T., MCHUTCHISON, J.G. and PANG, P.S., 2013. Efficacy of Nucleotide Polymerase Inhibitor Sofosbuvir plus the NS5A Inhibitor Ledipasvir or the NS5B Non-nucleoside Inhibitor GS-9669 Against HCV Genotype 1 Infection. Gastroenterology, .

KOWDLEY, K.V., LAWITZ, E., CRESPO, I., HASSANEIN, T., DAVIS, M.N., DEMICCO, M., BERNSTEIN, D.E., AFDHAL, N., VIERLING, J.M., GORDON, S.C., ANDERSON, J.K., HYLAND, R.H., DVORY-SOBOL, H., AN, D., HINDES, R.G., ALBANIS, E., SYMONDS, W.T., BERREY, M.M., NELSON, D.R. and JACOBSON, I.M., 2013. Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial. Lancet, 381(9883), pp. 2100-2107.

LAWITZ, E., POORDAD, F.F., PANG, P.S., HYLAND, R.H., DING, X., MO, H., SYMONDS, W.T., MCHUTCHISON, J.G. and MEMBRENO, F.E., 2013. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet, .

OSINUSI, A., MEISSNER, E.G., LEE, Y., BON, D., HEYTENS, L., NELSON, A., SNELLER, M., KOHLI, A., BARRETT, L., PROSCHAN, M., HERRMANN, E., SHIVAKUMAR, B., GU, W., KWAN, R., TEFERI, G., TALWANI, R., SILK, R., KOTB, C., WROBLEWSKI, S., FISHBEIN, D., DEWAR, R., HIGHBARGER, H., ZHANG, X., KLEINER, D., WOOD, B.J., CHAVEZ, J., SYMONDS, W.T., SUBRAMANIAN, M., MCHUTCHISON, J., POLIS, M.A., FAUCI, A.S., MASUR, H. and KOTTILIL, S., 2013. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA: The Journal of the American Medical Association, 310(8), pp. 804-811.

RODRIGUEZ-TORRES, M., LAWITZ, E., KOWDLEY, K.V., NELSON, D.R., DEJESUS, E., MCHUTCHISON, J.G., CORNPROPST, M.T., MADER, M., ALBANIS, E., JIANG, D., HEBNER, C.M., SYMONDS, W.T., BERREY, M.M. and LALEZARI, J., 2013. Sofosbuvir (GS-7977) plus peginterferon/ribavirin in treatment-naïve patients with HCV genotype 1: a randomized, 28-day, dose-ranging trial. Journal of Hepatology, 58(4), pp. 663-668.

10th Malaysia Genetics Congress | 3-5 December 2013 | Putrajaya, Malaysia

December 3, 2013, 6:24 am

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10th Malaysia Genetics Congress (MGC10)

Organisers: Persatuan Genetik Malaysia (Genetics Society of Malaysia)

Dates: December 3rd-5th 2013

Location: Palm Garden Hotel IOI Resort, Putrajaya, Malaysia

Website: http://www.persatuangenetikmalaysia.com/mgc10/
The website gives all the necessary information on conference agenda, hotel, exhibitions and other important facts.

Major theme
“Advances in Genetics, Biotechnology and Genomics”

Purpose of the conference
Researchers from around the world are today gathered for the 10th Malaysia Genetics Conference in order to “reflect on advances made in the scientific fields of genetics, biotechnology and genomics, consider the best of contemporary research progress and anticipate future development in these disciplines.” As they listen to more than 30 keynote and invited speakers, they will be anticipating the highlight of the conference, the 10th Mendel Lecture entitled ‘Frontline of Evolutionary and Comparative Genomics’ to be delivered by Professor Dr. Takashi Gojobori of the National Institute of Genetics, Japan
They will also have the opportunity to hear the following invited speakers:

Invited speakers
Prof. Dr. Finlay Macrae, The Royal Melbourne Hospital, Victoria, Australia
Prof. Dr. Hjh. Zohrah Hj. Sulaiman, Universiti Brunei Darussalam, Brunei
Prof. Dr. Ir. Alex Hartana, Bogor Agricutural University, Indonesia
Dr. Maria Viva Rini, Lampung University, Indonesia
Dr. Abdul Munir Abd. Murad, Universiti Kebangsaan Malaysia
Dr. Abdul Rahim Harun, Malaysian Nuclear Agency (Nuclear Malaysia)
Dr. Ahmad Parveez Ghulam Kadir , Malaysian Palm Oil Board
Dr. Chow Keng See. Malaysian Rubber Board
Dr. Harikrishna Kulaveerasingam . Sime Darby Technology Centre
Prof. Dr. Jennifer Ann Harikrishna, Universiti Malaya
Dr. Kodi Isparan Kandasamy, Malaysian Biotechnology Corporation (BiotechCorp)
Mr. Letchumanan Ramatha, Ministry of Natural Resources and Environment Malaysia
Dr. Mohd. Said Saad, Satiri Sdn Bhd
Prof. Dr. Mohd. Zaki Saleh, Universiti Teknologi MARA
Mr. Mohaimi Mohamad, Sime Darby
Dr. Michael Ling King Hwa, Universiti Putra Malaysia
Prof. Dr. Narazah Mohd. Yusoff, Universiti Sains Malaysia
Dr. Nor Azian Abdul Murad, UKM Medical Molecular Biology Institute (UMBI)
Dr. Norshariza Nordin, Universiti Putra Malaysia
Dr. Norwati Muhammad, Forest Research Institute Malaysia
AP. Dr. Shahrul Hisham Zainal Arif¬n, Universiti Kebangsaan Malaysia
Dr. Shawn Cheng, Forest Research Institute Malaysia
Prof. Dr. Siti Azizah Mohd. Nor, Universiti Sains Malaysia
Prof. Dr. Tajuddin Abdullah, Universiti Malaysia Sarawak
Dr. Teo Chee How, Agro-Biotechnology Institute Malaysia
Prof. Dr. Thong Meow Keong, Universiti Malaya
Dr. Zamri Ishak, Biotechnology Research Centre, MARDI
Prof. Dr. Zilfalil Alwi, Universiti Sains Malaysia

The scientific programme can be viewed here: http://www.persatuangenetikmalaysia.com/...gramme.pdf

Radioimmunotherapy provides hope of HIV cure

December 3, 2013, 11:00 am

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A patient process of establishing proof-of-principle for the effectiveness of targeting radiolabelled monoclonal antibodies to virally infected cells and then identifying monoclonal antibodies that would be effective against HIV infected cells is bearing fruit for researchers from Albert Einstein College of Medicine in New York in the USA. The group presented their findings on radioimmunotherapy (RIT) treatment of HIV-infected lymphocytes from patients previously treated with highly active antiretroviral therapy (HAART) at the Annual Meeting of the Radiological Society of North America (RSNA) today.

RIT is traditionally used in cancer treatment, but in 2006 the group published the findings of a proof-of-principle study in in vitro in chronically HIV-1-infected human T cells and acutely HIV-1-infected human peripheral blood mononuclear cells and in vivo in a severe combined immunodeficiency (SCID) mouse model in which there were acutely HIV-1-infected human peripheral blood mononuclear cells in the spleen. The group showed that using mAbs against HIV glycoproteins gp120 and gp41 labelled with bismuth 213 ((213)Bi) or rhenium 188 ((188)Re) resulted in killing of the HIV-1 infected cells and suggested that HIV-targeted RIT had potential as a co-treatment option along with HAART for HIV infection. The group then built on this proof-of-principle study to try to identify a mAb to HIV gp41 which would be suitable for preclinical development. mAB 2556 was identified as being a high affinity antibody which reacted with gp41 both on viral particle surfaces and infected cells. (213)Bi-2556 efficiently killed ACH-2 human lymphocytes chronically infected with HIV-1, and HIV-1 infected human peripheral blood mononuclear cells (hPBMCs) in vitro. In two in vivo HIV-1 mouse models, splenic and intraperitoneal, (213)Bi-2556 decreased HIV-1 infected hPBMCs from the spleens and peritoneum, respectively.

RIT had already been successfully adapted for the treatment of other pathogens such as experimental fungal (C. neoformans and H. capsulatum), bacterial (S. pneumoniae and B. anthracis), and viral (HIV-1) infections with negligible haematological toxicity in experimental animals. Depending on whether mAbs were radiolabeled with either alpha- or beta-emitters, infected cells succumbed to apoptosis-like cell death (both alpha- or beta-emitters), while mAbs radiolabeled with alpha-emitter (213)Bi also decreased the metabolic activity of microbial cells.

In the results presented in the Annual Meeting of the Radiological Society of North America (RSNA) the group reported that RIT killed previously HAART-treated HIV-infected lymphocytes and reduced HIV infection in the blood samples to undetectable levels. Their studies have also used an in vitro human blood brain barrier model to show that (213)Bi-2556 could cross the blood-brain barrier, thus potentially overcoming a limitation of anti-retroviral therapy, which can only partially cross the blood-brain barrier.

The effectiveness of this therapy lies in the fact that unlike HAART, the RIT can actually kill HIV-1-infected cells and eliminate reservoirs of latently HIV-infected cells that may persist even after HAART treatment. The group is preparing to move to clinical trials in patients to try out a strategy that may finally provide a cure for HIV infection.

Sources

DADACHOVA, E. and CASADEVALL, A., 2009. Radioimmunotherapy of infectious diseases. Seminars in nuclear medicine, 39(2), pp. 146-153.

DADACHOVA, E., KITCHEN, S.G., BRISTOL, G., BALDWIN, G.C., REVSKAYA, E., EMPIG, C., THORNTON, G.B., GORNY, M.K., ZOLLA-PAZNER, S. and CASADEVALL, A., 2012. Pre-clinical evaluation of a 213Bi-labeled 2556 antibody to HIV-1 gp41 glycoprotein in HIV-1 mouse models as a reagent for HIV eradication. Plos One, 7(3), pp. e31866-e31866.

DADACHOVA, E., PATEL, M.C., TOUSSI, S., APOSTOLIDIS, C., MORGENSTERN, A., BRECHBIEL, M.W., GORNY, M.K., ZOLLA-PAZNER, S., CASADEVALL, A. and GOLDSTEIN, H., 2006. Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. Plos Medicine, 3(11), pp. e427-e427.

http://www.sciencedaily.com/releases/201...091601.htm [Accessed 3 December 2013].

Transgenic animals in fertilized egg .. Need Answer

December 4, 2013, 2:05 am

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For making transgenic animals in fertilized egg,the best place to insert thr "trans gene " is in the female pronuclei or male pronuclei? and why?

Biotech Showcase™ 2014 | January 13-15 2014 | San Francisco

December 4, 2013, 3:22 am

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Biotech Showcase™ 2014

Organisers: EBD Group; Demy-Colton Life Science Advisors

Dates: January 13th-15th 2014

Location: Parc 55, Wyndham, San Francisco-Union Square, USA

Website: http://www.ebdgroup.com/bts/index.php
The website gives all the necessary information on agenda, company presentations, one-to-one meetings, registration fees, hotel, exhibitions and other important facts.

Major theme
Innovation – Opportunity – Collaboration

Purpose of the conference
Investors and pharmaceutical executives from all over the world will head over the Golden Gate Bridge and into San Francisco, between January 13th-15th 2014, for the important Biotech Showcase™ event. This event is one of the biotechnology industry’s largest annual healthcare investor conferences and its timing at the beginning of the year means that it is widely considered to influence the agenda and tone for the rest of the year. It is an investor and partnering conference which aims to give private and public biotechnology and life sciences companies the opportunity to present to, and meet with, investors and pharmaceutical executives. More than 1700 delegates are expected to attend, offering unprecedented opportunities to network and attract collaboration and investment.

Presenters
The conference offers presentation slots to private and public life science companies; there are still some slots left which will be awarded on a first-come, first-served basis. The types of companies showcased will fall into the following broad categories:

Categories:
• Small and large molecule R&D therapeutic companies
• Platform companies
• Tool companies
• Research focused service providers
• Molecular diagnostic companies
• Personalized medicine companies

Stage of Financing:
• Private
o A round to pre-IPO
• Public
o Micro-, small- and mid-cap

A list of the confirmed participating companies can be found here: http://www.ebdgroup.com/bts/participants/index.php

A list of the confirmed presenting companies can be found here: http://www.ebdgroup.com/bts/presenters/prs_comps.php

They include companies from countries including the USA, Belgium, the Netherlands, Finland, Ireland, Spain, Switzerland, France, Germany, Australia, New Zealand, Canada, UK, China and Japan.

Important dates
December 2nd 2013: Partnering opens; start requesting meetings
December 26th 2013: Deadline for meeting requests before first scheduling round
December 27th 2013: First round of partnering schedules available
January 10th 2014: Online registration ends
January 13th 2014: On-site registration begins

Avian flu virus re-emergence would present potential risk to under-50s

December 4, 2013, 3:58 am

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Often public health guidelines stress the vulnerability of older people to influenza infections and vaccine programmes are targeted towards elderly people and other vulnerable groups. However, a new study suggests that people under the age of 50 may be more vulnerable to infection if avian flu re-emerged in humans.

The study by researchers from St. Jude Children's Research Hospital in Memphis, Tennessee suggests that avian H2N2 viruses circulating in birds remain antigenically similar to the pandemic A/Singapore/57 (H2/N2) virus which caused a devastating pandemic, estimated to have killed 1-2 million people, when it emerged in humans in 1957-1958. This research group, who are a National Institute of Allergy and Infectious Diseases Centre of Excellence for Influenza Research and Surveillance, published their findings in the prestigious Journal of Virology, in an advance online edition. The study suggests that people under the age of 50 could be particularly vulnerable if the avian virus re-emerged in humans via ‘gene-swapping’ as younger people would have no previous exposure and therefore no humoral immunity to the virus.

The study findings were based on risk assessment of a panel of 22 avian H2N2 viruses isolated from both wild and domesticated birds over sixty years. The researchers found that the rate of antigenic and genetic evolution was very low, meaning that the viruses remain antigenically similar to the isolates in circulation at the time of the pandemic. Most of the isolates were able to replicate both in mice and human bronchial epithelial cells. Worryingly, many of them also replicated in ferrets, considered to be a reliable model for influenza replication in humans. The virus could be transmitted via direct contact between cage-mates but were not airborne. More reassuringly, the group did not observe markers of mammalian adaptation in the important proteins, haemagluttinin (HA) and the PB2 subunit of the viral RNA polymerase, in any isolates, and they retained a preference for avian-like α2-3 linked sialic acid receptors. Also, all were susceptible to anti-viral medications including neuraminidase inhibitors and adamantanes and their similarity to pandemic A/Singapore/1/57 (H2N2) virus suggests they would be controllable by the pandemic vaccine candidate.

Nevertheless, the group urges caution as the avian H2N2 viruses showed such a sustained pathogenicity in multiple mammalian models. Thus they still present a risk for human infection. The answer is for the public health and biotechnology community to be vigilant and maintain continual surveillance as part of pre-pandemic planning.

Sources

St. Jude Children's Research Hospital. "1950s pandemic influenza virus remains a health threat, particularly to those under 50." ScienceDaily, 3 Dec. 2013. [Accessed 4 Dec. 2013].

Jones, J.C., Baranovich, T., Marathe, B. M., Danner, A. F., Seiler, J. P., Franks, J., Govorkova, E. A., Krauss, S. and Webster, R. G., 2013. Risk Assessment of H2N2 Influenza Viruses from the Avian Reservoir. Journal of Virology, 2013; DOI: 10.1128/JVI.02526-13

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Cancer drug vorinostat shows promise in GVHD phase 1/2 trial

December 4, 2013, 4:52 am

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A drug currently approved for treatment of refractory cutaneous T-cell lymphoma has given promising results in reducing the incidence of graft-versus-host disease (GVHD) in bone marrow transplant patients. The study on the histone deacetylase inhibitor vorinostat was carried out by researchers in the University of Michigan Comprehensive Cancer Centre and published in The Lancet Oncology.

Vorinostat is a member of the family of histone deacetylase inhibitors (HDACi) which have both anti-cancer and anti-inflammatory properties. Many of these HDACi are in clinical trials for various cancers, including belinostat, abexinostat, SB939, resminostat, givinostat, quisinostat, pentobinostat, CUDC-101, with vorinostat (SAHA) having won FDA approval for cutaneous T-cell lymphoma (CTCL). HDACi compounds work by inducing histone lysine tails acetylation in chromatin and thereby modifying expression of genes involved in regulating processes relevant to cancer development, including cell survival, proliferation, differentiation and apoptosis. Vorinostat inhibits tumour cell growth and the production of pro-inflammatory cytokines. It was the anti-inflammatory effects of HDACi and their immunomodulatory function relating to balance of immune activation versus tolerance that prompted the study on vorinostat in GVHD. Acute GVHD remains highly problematic in using more general use of haemopoietic stem-cell transplantation.

Vorinostat had already been shown to attenuate GVHD in pre-clinical animal models. In the current study, a prospective, single-arm, phase 1/2 study was carried out at two centres in the USA on a cohort of 50 patients with high-risk haematological malignant diseases undergoing related-donor reduced-intensity conditioning haemopoietic stem-cell transplantation. Vorinostat was administered in combination with standard GVHD prophylaxis after transplantation. The primary end-point set for the study was cumulative incidence of grade 2—4 acute GVHD by day 100. Encouragingly, this was recorded at 22% of patients receiving vorinostat, compared to 42% who typically develop GVHD with standard medications alone. In terms of safety, the most common haematological grade 3—4 adverse event was non-symptomatic thrombocytopenia after engraftment but it was transient and quickly resolved in all cases.

The study’s authors caution that further studies are needed on this potential new application for vorinostat, for example in settings where haemopoietic stem-cell transplantation is carried out using non-related donors. They are however cautiously optimistic about the potential as the drug both because of its immunomodulatory function in reduction of GVHD coupled to its anti-cancer effects which may help in prevention of cancer relapse.Caution is also needed in any attempt to more generally apply HDACi compounds in treatment of GVHD as another study in mice unexpectedly showed that another HDACi, LBH589, accelerated GVHD.

Sources

CHOI, S.W., BRAUN, T., CHANG, L., FERRARA, J.L.M., PAWARODE, A., MAGENAU, J.M., HOU, G., BEUMER, J.H., LEVINE, J.E., GOLDSTEIN, S., COURIEL, D.R., STOCKERL-GOLDSTEIN, K., KRIJANOVSKI, O.I., KITKO, C., YANIK, G.A., LEHMANN, M.H., TAWARA, I., SUN, Y., PACZESNY, S., MAPARA, M.Y., DINARELLO, C.A., DIPERSIO, J.F. and REDDY, P., 2013. Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. The Lancet Oncology, 2013; DOI: 10.1016/S1470-2045(13)70512-6

IWAMOTO, M., FRIEDMAN, E.J., SANDHU, P., AGRAWAL, N.G.B., RUBIN, E.H. and WAGNER, J.A., 2013. Clinical pharmacology profile of vorinostat, a histone deacetylase inhibitor. Cancer chemotherapy and pharmacology, 72(3), pp. 493-508.

LICCIARDI, P.V., VERVERIS, K., TANG, M.L., EL-OSTA, A. and KARAGIANNIS, T.C., 2013. Immunomodulatory effects of histone deacetylase inhibitors. Current Molecular Medicine, 13(4), pp. 640-647.

RAJAK, H., SINGH, A., RAGHUWANSHI, K., KUMAR, R., DEWANGAN, P.K., VEERASAMY, R., SHARMA, P.C., DIXIT, A. and MISHRA, P., 2013. A Structural Insight into Hydroxamic Acid Based Histone Deacetylase Inhibitors for the Presence of Anticancer Activity. Current medicinal chemistry, 2013.

REDDY, P., DE LIMA, M. and KORETH, J., 2012. Emerging therapies in hematopoietic stem cell transplantation. Biology Of Blood And Marrow Transplantation: Journal Of The American Society For Blood And Marrow Transplantation, 18(1), pp. S125-S131.

WANG, D., ICLOZAN, C., LIU, C., XIA, C., ANASETTI, C. and YU, X., 2012. LBH589 enhances T cell activation in vivo and accelerates graft-versus-host disease in mice. Biology Of Blood And Marrow Transplantation: Journal Of The American Society For Blood And Marrow Transplantation, 18(8), pp. 1182-1190.e1.

University of Michigan Health System. "New drug cuts risk of deadly transplant side effect in half." ScienceDaily, 2 Dec. 2013. [Accessed 4 Dec. 2013].

Sucessful inheritance of transgenic material in mouse sperm

December 5, 2013, 5:19 am

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A research group from The Royal Veterinary College, North Mimms in the UK has just published a ground-breaking transgenics paper. The paper, published in in The FASEB Journal, reported the results of a study on mouse sperm transfected with lentivirus in which the authors show that transgenes could be transmitted to a second and third generation of mice. The group used lentivirus vectors encoding the marker green fluorescent protein (GFP) to transduce mouse spermatozoa. These spermatozoa were then used in in vitro fertilisation procedures. Following implantation, greater than 42% of the resulting founders were transgenic for GFP. Expression was observed on different chromosomes and in multiple tissues, including testis. It even extended to a third generation of mice.

This work opens up the possibility of using the relatively accessible male germ cells, including mature sperm, instead of oocytes as a substrate for transgenics. It is a relatively simple technique but its implications are huge, especially if it proves transferable to humans. The authors of the study point to the applicability of the technique the study of fertilization and pre-implantation, vertical viral gene transmission, gene function and regulation, and epigenetic inheritance. Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal points out that “If we are able to able to alter sperm to improve the health of future generations, it would completely change our notions of 'preventative medicine’." If it is transferable, the sky is the limit for this technology which opens up the possibility of using transgenics to potentially cure diseases and, for example, regenerate human organs.

Sources
Chandrashekran, A., Sarkar, R., Thrasher, A., Fraser, S.E., Dibb, N., Casimir, C., Winston, R. and Readhead, C., 2013. Efficient generation of transgenic mice by lentivirus-mediated modification of spermatozoa. FASEB J, December 2, 2013 DOI: 10.1096/fj.13-233999

Federation of American Societies for Experimental Biology. "'Designer sperm' inserts custom genes into offspring." ScienceDaily, 2 Dec. 2013. [Accessed 5 Dec. 2013].

Cell Based Assays Congress 2014 Europe | February 27-28 2014 | London UK

December 5, 2013, 6:22 am

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Cell Based Assays Congress 2014 Europe

Organisers: Paradigm Global Events

Dates: February 27th-28th 2014

Location: Holiday Inn Bloomsbury, London, UK

Website: http://www.paradigmglobalevents.com/even...13-europe/
The website gives all the necessary information on abstract submission, conference agenda, hotel, exhibitions and other important facts.

Who should attend?
Presidents, Chief Executives, Chief Scientific Officers, Chief Operating Officers, Vice Presidents, Senior Vice Presidents, Heads, Senior Directors, Directors, Clinicians, Principal Scientists, Principal Investigators, Managers, Project /Team Leaders in:
• High-Throughput / High – Content Screening Operations
• GPCR / Kinases / Molecular Pharmacology
• Stem Cell Technologies & Platforms
• Bioanalytical Development
• Toxicology and Safety Testing
• Pharmacovigilance and Safety Testing
• In Vitro Sciences
• Drug Delivery
• Drug Discovery / Validation
• Drug Development
• Antibody Discovery
• ADMET
• Pre-clinical Development
• Medical Chemistry
• Compound Profiling
• Cellular Imaging
• Lead Generation
• Pharmacodynamics
• Pharmacokinetics
• External/Contract Research
• Medical Chemistry
• Chemistry and Bioapplications
• Global Research and Development
• Business Development
• Investment and Venture Capital
• Neuroscience – Preclinical & Biomarkers
• Neurodegenerative and Neurological Diseases

Purpose of the conference

This conference aims to explore the latest thinking and techniques in the field of cell-based assays. Companies have become more aware of the utility of these types of assays in reducing the number of clinical candidates that do not progress through the pipeline, as the assays demonstrably prove leads have a clinical effect. The event will cover a multitude of topics including: ion channel assays, 3D assays, GPCR, as well as stem cell assays. It will also address subjects such as: post-analytics, quality control, and outsourcing. The conference also offers networking opportunities with professionals in the field.

Key speakers
• Professor Paul French – Photonics Group, Physics Department, Imperial College London
• Dr. David Hay – Principal Investigator, MRC Centre for Regenerative Medicine, University of Edinburgh
• Dr Sheraz Gul, CChem MRSC, CSi, European ScreeningPort GmbH
• Grant Cameron, PhD – RAFT Development Director, Tap Biosystems
• Dr. Anthony Davies, Director of the High Content Facility, Institute of Molecular Medicine, Trinity College Dublin
• Dr. Olivier Pardo, Team Leader, Lecturer, Division Cancer, Imperial College London
• Farnaz Fallah-Arani, Dept. of Pharmacology at UCB Celltech, Slough, UK
• Michael Dabrowski, PhD, CEO Pelago Biosciences
• Dr. Rozbeh Jafari, PhD, Post Doc, Karolinska Institute

New method for scoring tumour infiltrating cells and ovarian cancer prognosis

December 6, 2013, 3:01 am

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A new study from researchers in the Fred Hutchinson Cancer Research Center, Seattle, USA and the University of Washington, Seattle has developed a DNA-based assay, in order to reliably count tumour-infiltrating lymphocytes (TILs) and asses their T cell clonality. This should help with use of TILs as a reliable prognostic biomarker in cancer. The study, published this week in the journal Science Translational Medicine addresses technical issues that have previously made quantification of TILs and scoring of their presence in tumours difficult and inconsistent.

It is generally agreed that TIL infiltration is correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC). EOC is one of the most deadly gynaecological tumours and prognosis based on clinicopathological features is difficult. A previous study used deep sequencing of rearranged T-cell receptor beta (TCRB) genes to characterise TILs in ovarian carcinoma. It was shown that the TIL repertoires are similar throughout ovarian carcinomas but distinct from the repertoire in circulating T cells. That study concluded that there was a distinct cellular adaptive immune response within ovarian carcinomas mediated by TILs. Autoantibodies are another form of defence against EOC and a study showed that autoantibodies to the common tumour antigen NY-ESO-1 correlates with TILs in solid tumour and ascites in tissue samples from high-grade serous ovarian cancer. This suggests that TILs and autoantibodies may cooperate in a host cancer immune response against tumour antigens.

In the current Science Translational Medicine study, the authors addressed the problem of limited inclusion of TILs in standard prognostic panels due to difficulties in reliably counting them and lack of consistent criteria in scoring TILs across studies. The study introduced a robust digital DNA-based assay, termed QuanTILfy, to count TILs and assess T cell clonality in tissue samples, including tumours. The researchers used tumour samples from 30 ovarian cancer patients whose survival outcomes were known and were able to make accurate, sensitive, and highly reproducible measurement of TILs in both primary and metastatic ovarian cancer. They confirmed that there was a direct relationship between higher TIL counts and improved survival among women with ovarian cancer. They observed that, surprisingly, the TIL repertoire was diverse for all tumours in the study.

The authors conclude that the development of a sensitive, standardisable and reproducible DNA-based assay such as their QuanTILfy should enable TILs to be used a prognostic indicator in a range of cancer types including ovarian cancer. This should in turn help in decisions about patient care and treatment.

Sources

ROBINS, S., ERICSON, N. G., GUENTHOER, J., O’BRIANT, K. C. , TEWARI, M., DRESCHER, C. W. and BIELAS, J. H., 2013. Digital Genomic Quantification of Tumor-Infiltrating Lymphocytes. Sci. Transl. Med. 5, 214ra169 (2013).

BACHMAYR-HEYDA, A., AUST, S., HEINZE, G., POLTERAUER, S., GRIMM, C., BRAICU, E.I., SEHOULI, J., LAMBRECHTS, S., VERGOTE, I., MAHNER, S., PILS, D., SCHUSTER, E., THALHAMMER, T., HORVAT, R., DENKERT, C., ZEILLINGER, R. and CASTILLO-TONG, D., 2013. Prognostic impact of tumor infiltrating CD8+ T cells in association with cell proliferation in ovarian cancer patients - a study of the OVCAD consortium. BMC Cancer, 13, pp. 422-422.

EMERSON, R.O., SHERWOOD, A.M., RIEDER, M.J., GUENTHOER, J., WILLIAMSON, D.W., CARLSON, C.S., DRESCHER, C.W., TEWARI, M., BIELAS, J.H. and ROBINS, H.S., 2013. High-throughput sequencing of T cell receptors reveals a homogeneous repertoire of tumor-infiltrating lymphocytes in ovarian cancer. The Journal of Pathology, 2013.

MILNE, K., BARNES, R.O., GIRARDIN, A., MAWER, M.A., NESSLINGER, N.J., NG, A., NIELSEN, J.S., SAHOTA, R., TRAN, E., WEBB, J.R., WONG, M.Q., WICK, D.A., WRAY, A., MCMURTRIE, E., KöBEL, M., KALLOGER, S.E., GILKS, C.B., WATSON, P.H. and NELSON, B.H., 2008. Tumor-infiltrating T cells correlate with NY-ESO-1-specific autoantibodies in ovarian cancer. Plos One, 3(10), pp. e3409-e3409.

Fred Hutchinson Cancer Research Center. "Predicting ovarian cancer survival by counting tumor-attacking immune cells." ScienceDaily, 4 Dec. 2013. [Accessed 6 Dec. 2013].

Camelid single domain antibody (sdAb) service by GenScript

December 10, 2013, 6:40 pm

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The use of camelid heavy chain antibodies (HCAbs) in antibody engineering is becoming popular. It differs from standard IgG antibodies in that it is significantly smaller, with 6 total domains that consist of two heavy chains, each with a variable region (VHH) and two constant regions (CH2 and CH3). The VHH domain is actually a fully functional antibody fragment, hence its name single domain antibody (sdAb).

Because of its small 13kDa size, sdAbs have the advantage of better tissue penetration, and binding to hidden epitopes. An example of this is in HIV-1 vaccine development. Researchers have discovered that these small single domain antibodies can bind to the gp140 envelope glycoprotein to prevent interaction with cell CD4 receptors and neutralize over 95% of circulating HIV-1 isolates*.

SdAbs are revolutionizing the next-generation of antibody therapeutics and GenScript is pleased to offer sdAb engineering services along with our other cutting-edge antibody engineering services and expertise.