gentaur-antibodies-elisa-cellculture-gene modification-pcrCancer drugs of the new, molecular generation destroy malignant breast tumors in a targeted manner: They block characteristic molecules on tumor cells - receptors for the hormones estrogen or progesterone, or a co-receptor, called HER2, that binds to many growth factors. But about one in every six breast tumors has none of these receptors. Such cancers, called triple-negative, are particularly aggressive and notoriously difficult to treat.
Some of these therapy-resistant cancers have a potential molecular target for cancer drugs, a growth-factor receptor called EGFR, but an EGFR-blocking drug has proved ineffective in treating them. In a study published recently in the Proceedings of the National Academy of Sciences, Weizmann Institute researchers propose a potential solution: to simultaneously treat triple-negative breast cancer with two EGFR-blocking antibodies instead of one. In a study in mice, the scientists showed that a certain combination of two antibodies indeed prevented the growth and spread of triple-negative tumors. The research team, led by Prof. Yosef Yarden of the Biological Regulation Department and Prof. Michael Sela of the Immunology Department, included Drs. Daniela Ferraro, Nade`ge Gaborit, Ruth Maron, Hadas Cohen-Dvashi, Ziv Porat, Fresia Pareja, and Sara Lavi, Dr. Moshit Lindzen and Nir Ben-Chetrit.
Of the different combinations they tried, the scientists found that the approach worked when the two antibodies bound to different parts of the EGFR molecule. The combined action of the antibodies was stronger than would have been expected by simply adding up the separate effects of each. Apparently, the use of the two antibodies created an entirely new anti-cancer mechanism: In addition to blocking the EGFR and recruiting the help of immune cells, the antibodies probably overwhelmed the EGFR by their sheer weight, causing it to collapse inward from the membrane into the tumor cell.
Deprived of EGFR on its surface, the cells were no longer receiving the growth signals, preventing the growth of the tumor. This approach resembles the natural functioning of the immune system, which tends to block essential antigens at several sites by targeting them with multiple antibodies. If supported by further studies, the two-antibody approach, in combination with chemotherapy, might in the future be developed into an effective treatment for triple-negative breast cancer.

Published in News

gentaur-tobacco-antibodies-gene-elisa-cellculture-pcr-assay kits

Smoking tobacco might be bad for your health, but a genetically altered version of the plant might provide a relatively inexpensive cure for the deadly rabies virus. In a new research report appearing in The FASEB Journal, scientists produced a monoclonal antibody in transgenic tobacco plants that was shown to neutralize the rabies virus. This new antibody works by preventing the virus from attaching to nerve endings around the bite site and keeps the virus from traveling to the brain.
"Rabies continues to kill many thousands of people throughout the developing world every year and can also affect international travelers," said Leonard Both, M.Sc., a researcher involved in the work from the Hotung Molecular Immunology Unit at St. George's, University of London, in the United Kingdom. "An untreated rabies infection is nearly 100 percent fatal and is usually seen as a death sentence. Producing an inexpensive antibody in transgenic plants opens the prospect of adequate rabies prevention for low-income families in developing countries."
To make this advance, Both and colleagues "humanized" the sequences for the antibody so people could tolerate it. Then, the antibody was produced using transgenic tobacco plants as an inexpensive production platform. The antibody was purified from the plant leaves and characterized with regards to its protein and sugar composition. The antibody was also shown to be active in neutralizing a broad panel of rabies viruses, and the exact antibody docking site on the viral envelope was identified using certain chimeric rabies viruses.
"Although treatable by antibodies if caught in time, rabies is bad news," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "This is especially true for people in the developing world where manufacturing costs lead to treatment shortages. Being able to grow safe, humanized antibodies in genetically modified tobacco should reduce costs to make treatments more accessible, and save more lives."

Published in News
Thursday, 14 February 2013 10:22

JX-594 Anti-Cancer Virus Found in Canada

antibodies-jx-594 cancer-cellsRecent news suggests that Canadian Cancer Specialists have found what researchers have labelled a medical first, in that an engineered virus which is injected into the cancer patients blood stream targets cancer cells throughout the body killing them, or at least not letting them get any bigger. Out of 23 patients, who have highly metabolized cancer, which means that the cancer has spread throughout their body and doesn’t show signs of being decreased, have been injected with a cancer fighting virus which hopes to kill the cancer cells. This is not the first time that a cancer virus has been suggested to the public. However, normally with cancer viruses, the virus itself had to be administered and injected directly into the tumor. This is extremely difficult as, tumors are not always stationary within the human body. The anti-cancer virus JX-594 was injected into the blood of 23 patients. 8 out of the 23 patients had the JX-594 replicating itself inside the cancer tumors, and not spreading into other healthy non-cancer cells.

"We are very excited because this is the first time in medical history that a viral therapy has been shown to consistently and selectively replicate in cancer tissue after intravenous infusion in humans.” Said, Professor John Bell, who is the lead research from the University of Ottawa. Professor Nick Lemoine, director of Barts Cancer Institute said, “Viruses that multiply in just tumor cells - avoiding healthy cells - are showing real promise as a new biological approach to target hard-to-treat cancers. This new study is important because it shows that a virus previously used safely to vaccinate against smallpox in millions of people can now be modified to reach cancers through the bloodstream - even after cancer has spread widely through the patient's body. "It is particularly encouraging that responses were seen even in tumors like mesothelioma, a cancer which can be particularly hard to treat."

What happened to the other 15 patients who did not show sign of progress? Well...it’s not said. However, 6 of the patients did have infection which prevented the growth of any tumor progress. JX-594 was only given to the 23 patients at a small does, and only one does, because it is so early in the stages.
 

Dose-Finding Results

Oncolytic immunotherapies are designed to selectively replicate within cancer cells and, subsequently, to lyse them, Dr. Reid and colleagues explain. JX-594 is designed to induce virus-replication-dependent oncolysis and tumor-specific immunity, and to disrupt the "viral thymidine kinase gene for cancer selectivity and insertion of human granulocyte-macrophage colony-stimulating factor (hGM-CSF) and beta-galactosidase transgenes for immune stimulation and replication assessment, respectively," they note.

The complete response of bulky tumors and systemic efficacy was seen in phase 1 trials of JX-594.

In this phase 2 trial, 30 patients with advanced HCC received 1 of 2 injections into liver tumors on days 1, 15, and 29: low-dose JX-594 (108 pfu) or high-dose JX-594 (109 pfu).

Kaplan–Meier survival estimates were significantly longer in the high-dose group than in the low-dose group at 1 year (66% vs 23%) and at 18 months (35% vs 11%). Survival did not correlate with the origin of the tumor.

In the 19 patients with multiple tumors at baseline (10 in the high-dose group and 9 in the low-dose group), median overall survival was longer in the high-dose group (13.6 vs 4.3 months; HR, 0.19; P = .018).

Median survival in patients with multiple tumors was half that of patients with single tumors (8.8 vs 16.6 months). The authors note that there was no correlation between survival duration and the presence of detectable neutralizing antibodies to the vaccinia virus at baseline, compared with the absence of such antibodies (HR, 0.68)

Both doses of JX-594 were generally well tolerated, Dr. Reid and colleagues report, and there were no treatment-related deaths. One patient in the high-dose group experienced a treatment-related serious adverse event (nausea and vomiting requiring prolonged hospitalization), and 8 patients (4 in each group) experienced nontreatment-related serious adverse events.

Antiangiogenesis Results

In the phase 2 antiangiogenesis trial, Dr. Breitbach and colleagues tested the hypothesis that a vaccinia virus engineered to target cells that activate the ras/MAPK signaling pathway would specifically infect and express transgenes (hGM-CSF, beta-galactosidase) in tumor-associated vascular endothelial cells in humans.

Preclinical research in mice demonstrated that an intravenous infusion of JX-594 resulted in virus replication in tumor-associated endothelial cells, disruption of tumor blood flow, and hypoxia within 48 hours, and massive tumor necrosis within 5 days. In a phase 1 clinical trial, an intravenous infusion of JX-594 showed dose-dependent endothelial cell infection in tumors.

 

Dr. Breitbach and colleagues found that JX-594 disrupted perfusion to the tumor as soon as 5 days after treatment in both VEGF-receptor inhibitor-naïve and -refractory patients with advanced HCC.

This "technology opens up the possibility of multifunctional engineered vaccinia products that selectively target and infect tumor-associated endothelial cells, as well as cancer cells, resulting in transgene expression, vasculature disruption, and tumor destruction in humans systemically," they note.

Funding for the dose-finding study was provided by Jennerex, Transgene SA, and the Green Cross Corporation. Several coauthors report receiving individual grants, as detailed in the paper.

Published in News
Sunday, 10 February 2013 17:44

Two Antibodies Are Better Than One

A new approach mimicking the body’s natural defenses could help treat a therapy-resistant breast cancer

Cancer drugs of the new, molecular generation destroy malignant breast tumors in a targeted manner:  They block characteristic molecules on tumor cells – receptors for the hormones estrogen or progesterone, or a co-receptor, called HER2, that binds to many growth factors. But about one in every six breast tumors has none of these receptors. Such cancers, called triple-negative, are particularly aggressive and notoriously difficult to treat.

Some of these therapy-resistant cancers have a potential molecular target for cancer drugs, a growth-factor receptor called EGFR, but an EGFR-blocking drug has proved ineffective in treating them. In a study published recently in the Proceedings of the National Academy of Sciences, Weizmann Institute researchers propose a potential solution: to simultaneously treat triple-negative breast cancer with two EGFR-blocking antibodies instead of one. In a study in mice, the scientists showed that a certain combination of two antibodies indeed prevented the growth and spread of triple-negative tumors. The research team, led by Prof. Yosef Yarden of the Biological Regulation Department and Prof. Michael Sela of the Immunology Department, included Drs. Daniela Ferraro, Nadège Gaborit, Ruth Maron,  Hadas Cohen-Dvashi,  Ziv Porat and Fresia Pareja, and Sara Lavi, Dr. Moshit Lindzen and Nir Ben-Chetrit.

Of the different combinations they tried, the scientists found that the approach worked when the two antibodies bound to different parts of the EGFR molecule. The combined action of the antibodies was stronger than would have been expected by simply adding up the separate effects of each.  Apparently, the use of the two antibodies created an entirely new anti-cancer mechanism: In addition to blocking the EGFR and recruiting the help of immune cells, the antibodies probably overwhelmed the EGFR by their sheer weight, causing it to collapse inward from the membrane into the tumor cell.
 
Deprived of EGFR on its surface, the cells were no longer receiving the growth signals, preventing the growth of the tumor. This approach resembles the natural functioning of the immune system, which tends to block essential antigens at several sites by targeting them with multiple antibodies.

If supported by further studies, the two-antibody approach, in combination with chemotherapy, might in the future be developed into an effective treatment for triple-negative breast cancer.
Prof. Michael Sela is the incumbent of the W. Garfield Weston Professorial Chair of Immunology.
Prof. Yosef Yarden’s research is supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; the M.D. Moross Institute for Cancer Research; the Steven and Beverly Rubenstein Charitable Foundation , Inc.; Julie Charbonneau, Canada; the European Research Council; and the Marvin Tanner Laboratory for Research on Cancer. Prof. Yarden is the incumbent of the Harold and Zelda Goldenberg Professorial Chair in Molecular Cell Biology.
 
 
Published in News
Friday, 08 February 2013 12:32

Kronos Dio

A luminometer for real-time reporter assay with 8 dish incubator and multicolor measurement system

Kronos dio AB-2550-kronosDioA luminescence monitoring tool to observe gene expressions with bioluminescent markers under long-term culture. Can be used in studies of internal biological clock, circadian rhythms in organisms, gene silencing, drug stimulation, etc. Kronos Dio is equiped with cell culture system within its housing to provide real-time periodical luminescence measurement with multi-color luciferase assay, enabling users to analyse the effects of complex factors influencing gene expression in the cell or the tissue. Internal temperature control (range: 20 to 45 °C) and carbon dioxide circulation allows for convenient cell culture over a long period of time.

 

Price: 29 500 Euro / 36 000 USD / 27 600 GBP

 

kronos-dio-gentaur-colours 

Installation and training

For the price GENTAUR provides notebook, installation and training (demonstration of basic software and hardware functionality). 6 hours of installation and training is inclusive in the price at no extra cost for USA and Europe. The necessary materials and tools for connecting the device to the Carbone dioxide source at the expense of the customer.

20141105 033403

kronos dio installation

kronos dio installationkronos dio installation kronos dio installation

 

 

 

 

Download Catalogue

 

See also: Cellgraph AB-3000B

Literature

Customer references:

Aaron Rowland, Ph.D.
Assistant Professor of Toxicology
Department of Chemistry & Biochemistry
New Mexico State University
1175 North Horseshoe Drive
P.O. Box 30001
Las Cruces, NM 88003-8001


We are wanting to explore the ability of human breast cell lines to exhibit circadian rhythm.  We are also interested in influence of environmental toxicants on circadian rhythm as well as general gene regulation.  I felt that the Kronos dio would be the proper equipment to perform this task as it has a CO2 hook up and can monitor 3 colors at once.  Therefore, I could transfect the BASIC luciferase construct using one color and the gene of interest using a different luciferase and monitor reporter activity in real time.  
Observation that Irritant of Environmental toxin on Human’s breast cell lines reaction and changes.

 

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Published in Promos

The quest for longer and healthier life, if not immortality, has been part of the human experience since we evolved the ability to recognize the total annihilation of individual death. Our understanding of the biology of aging at the molecular level is advancing so rapidly that it appears inevitable that another decade or two of life will be enabled before long. A new step in what may be the right direction has just been published by researchers at the University of California, Berkeley.

The ravages of aging appear to be related to oxidative stress combined with telomere exhaustion, along with many other known and unknown factors. The subject of the new Berkeley study is a class of proteins called sirtuins that are known to play a central role in regulating aging and longevity in many non-human models (such as mice).

There is good evidence that these proteins also play a similar role in humans. For example, research has shown that, of two variants of the SIRT3 sirtuin protein (known to have strong anti-oxidant properties), humans who live past 90 years of age only have one of the variants in their bodies, the variant that enhances production of SIRT3. The difference between the two variants results from a change of one gene by one mutation, and appears to be sufficient to significantly affect an organism's longevity. This suggests a strong link between SIRT3 and longevity.

The genetics of longevity are quite interesting, but still more interesting would be finding an approach to offset the hand you were dealt at birth, or better yet, to stack the deck. The authors of the Berkeley study decided to see if SIRT3 could rejuvenate blood stem cells extracted from old mice.

Their first step was to see what happened as mice, which did not possess the SIRT3 gene, aged. When young, these "knockout" mice followed the same course of aging as did a set of normal control mice. However, when the mice were two years old (about an average lifespan for a lab mouse), the knockout mice had far fewer blood stem cells than did the control group.

What causes the difference in the course of aging? Young cells have low levels of oxidative stress (the generation of reactive oxygen species during metabolism), low enough that the body's normal anti-oxidants can keep up with the resulting damage. When they get older, they can't keep up, and need a boost of SIRT3 to help them. When there is no SIRT3, the progress of old age occurs sooner and more rapidly.

“When we get older, our system doesn’t work as well, and we either generate more oxidative stress or we can’t remove it as well, so levels build up,” said Chen. “Under this condition, our normal anti-oxidative system can’t take care of us, so that’s when we need SIRT3 to kick in to boost the anti-oxidant system. However, SIRT3 levels also drop with age, so over time, the system is overwhelmed.”

So it appears that age-related degeneration speeds up in the absence of SIRT3 in the system – at least among mice. The Berkeley team decided to see if increasing SIRT3 levels could rehabilitate the blood stem cells. This was done by infusing the blood stem cells with the SIRT3 protein, following which their ability to make new blood cells did indeed return.

Further studies will address if SIRT3-induced rejuvenation will apply to whole organisms, so that they might live longer when so treated, even after experiencing normal aging events.

Published in News
Wednesday, 06 February 2013 15:35

RunBlue DTT Reducer - 1ml

Catalog number : NXA32001 
Availability: Yes 

Details: All RunBlue Buffers, Reagents and Accessories have been specifically designed and formulated for use with the RunBlue Gels and Apparatus to provide optimum performance and results.  Buffers are made usiong the highest qualtiy raw chemicals and have different compositions to other manufacturers buffers - only use RunBlue formulated buffers with RunBlue Gels.

RunBlue RAPID Running Buffer is a Reducing, Tris-MOPS buffer system which provides a seperation similar to a conventional MES buffer system and provides excellent separation of low molecular weight proteins.  The RunBlue SDS Running Buffer is a Non-Reducing Tris-Tricine buffer system which provides a separation similar to a conventional MOPS buffer system and provides increased separation of higher molecular weight proteins.  Simply choose which buffer will provide the greatest resolution for your protein(s) of interest - see image below.

SDS-vs-RAPID-Buffers Plain

Included with the reagents are RunBlue Prestained Markers.  These protein standards have been conjugaded to dyes to enable visualisation of the marker bands in the tank and prior to staining to allow you to see where your protein has reached (very useful for very small proteins!).  In addition, the RunBluePrestain Markers contain two standards (71 & 28 kDa) that have been conjugated to an orange dye to easily see which marker is which during running.

RunBlue Prestained Markers also offer a quick and convenient method to confirm transfer efficiency when blotting and to compare molecular weight with identity when labelling the protein band.

 

 Price: 50 EUR

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Published in Top Products
Wednesday, 06 February 2013 14:34

PSA ELISA Kit 96t

Human-ELISA

Catalog number : 2125-96T
Quantity:
Availability: Yes

Details: This kit is a solid phase-phase sandwich enzyme linked immuno sorbent assay (ELISA). Samples, including standards of known target protein concentrations and unknowns are pipetted into these wells. During the first incubation, the target protein antigen and a biotinylated monoclonal antibody specific for target protein are simultaneously incubated. After washing, the enzyme (streptavidin-peroxydase) is added. After incubation and washing to remove the entire unbound enzyme, a substrate solution which is acting on the bound enzyme is added to induce a colored reaction product. The intensity of this colored product is directly proportional to the concentration of target protein present in the samples.

 

 Price: 173 EUR

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Published in Top Products
Wednesday, 06 February 2013 14:09

Bacteriological Peptone - 500 grams

Catalog number : 1616
Quantity: 500 grams
Availability: Yes

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Details: Bacteriological Peptone it is an standardized peptone for the preparation of bacteriological culture media. The Nitrogen it contains is perfectly available for the bacterial growth requirements. It is completely soluble giving a transparent solution at the concentrations used in culture media.

 Price: 66 EUR

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Published in Top Products
Wednesday, 06 February 2013 12:34

GMP IL4 50µg -25°C

Catalog number : 04-GMPhuIL4-50 µg
Quantity: 50 µg
Availability: Yes

Description: Recombinant Human IL-4 produced in E.Coli is a single, non-glycosylated polypeptide chain containing 130 amino acids and having a molecular mass of 15000 Dalton. The rHuIL-4 is purified by proprietary chromatographic techniques.

Source : E.coli

Molecular weight : 15 KDa

Identity : rh IL-4 as measured by Elisa and Western Blot

Specific activity : > 13.10 units/mg compared to NIBSC  standard . CT-h4.S cell  proliferation assay. 650 000 IU /vial

Purity : > 98% as determined by SDS-PAGE and HPLC

Endotoxin content : < 0.1 EU/ µg of IL-4 (LAL test)

Host DNA : < 10 pg/ng protein

Sterility : sterile according to EP Test 2.6.1.

Stabiliser : contains Trehalose  ;  no preservative.

Physical state : freeze-dried

Stability : 12 months at – 20°C to – 80°C

3 months after reconstitution with  water for injection ( as defined in  EP Monograph    0169) when stored at -80°C

Reconstitution : use 500 µL water for injection in class A environment in order to keep  the GMP grade .

Packaging unit : 50 µg protein (Lowry test)  

GMP:

GENTAUR rh IL-4 is manufactured in full compliance with cGMP in facilities approved by the Belgian Ministry of Health for the production and storage of medicinal products.

Use: GENTAUR rh IL-4 is not an approved medicinal product and cannot be injected as such to patients.

FOR EX VIVO CELL CULTURE AND FOR IN VITRO RESEARCH USE ONLY

 Price: 482 EUR

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Published in Top Products