We at Novus Biologicals are one of the leading antibody suppliers for products targeted to apoptosis i.e. programmed cell death. These products are regularly used by cancer research groups – apoptosis is fundamental to developing therapies that will kill tumour cells. Caspase proteins, which play a key role in apoptosis, are therefore regularly featured in our antibody catalogue.

The caspases collectively belong to the cysteine protease enzyme family, and exist normally in an inactive state, until activated. They can be divided into three groups: initiator caspases, effector caspases and cytokine processors. Initiators are the first to be activated. They then cleave the effectors, which in turn cleave and activate apoptosis-promoting proteins. The cytokine processors (CPs) are a specialised group which play a role in the inflammatory response by activating pro-inflammatory cytokine proteins. They include Caspase-1, 4, 5, and 11 to 14.

Caspases are widely used as biomarker proteins, owing to the number of ways in which they can be activated and the morphological changes they promote within the cell. These include DNA fragmentation, chromatin condensation, plasma membrane blebbing and cell shrinkage. They have recently become important tools for cancer research.

Biomarker antibodies have been used in cancer research for some time. They are used to identify primary tumour cell proteins, track metastasis and analyse molecular alterations such as changes in up/down regulation of apoptosis proteins and unwarranted inflammatory responses. Caspase biomarkers are therefore an important oncological tool.

Recent studies suggest Caspase-1 could be a useful cancer biomarker. Antibody assays have shown it expressed in certain colon carcinomas, and localised at TAM (Tyrosine, Axl and Mer) receptors in others. We at Novus Biologicals anticipate that our new Capsace antibodies will be important to cancer research in the future.

We at Novus Biologicals recently added two new MCP-1 (Monocyte chemotactic protein-1) antibodies to our antibody catalogue. MCP-1, also known as MCAF (monocyte chemotactic and activating factor) is released by a diverse range of cell types as part of the inflammatory response. A member of the SIG (small inducible gene) family, it is selective for monocytes and basophils, mainly to recruit monocytes to injury and infection sites.

In a pathological role, MPC-1 is implicated in various diseases in which monocytic infiltrates are expressed, such as atherosclerosis and rheumatoid arthritis. Elevated levels have been found in joints of rheumatoid arthritis sufferers, where antibody studies suggest its function is to recruit macrophages and stimulate inflammation within the joints. Elevated levels have also been found in the urine of lupus sufferers, pointing to its role in kidney inflammation.

However, studies have also shown MCP-1 to play a role in augmenting monocytic anti-tumour activity. In 2003, the Cancer Gene Therapy online journal reported the enhanced anti-tumour effects of adenovirus-expressed MCP-1 against hepatocellular carcinomas.

At that time, “suicide gene” cancer therapy using an HSV-tk/GCV (herplex simplex virus/ganciclovir) system was showing limited success. Antibody studies were therefore conducted to see if the anti-tumour action could be enhanced by expressing HSV-tk and MCP-1 genes, using rAD (recombinant adenovirus vector). The results suggested MCP-1 could enhance the anti-tumour effects of gene therapy by macrophage activation. MCP-1 production coincided with raised levels of macrophages and TNF-1 (tumour necrotising factor). Furthermore, deactivation of macrophages negated the anti-tumour effect.

Additionally, in vivo mouse studies, using MCP-1 antibody products, have shown that MCP-1 vaccination promotes monocyte and killer cell migration into human tumour cells.

Supplying antibodies for neuroscience research forms an important part of our work here at Novus Biologicals. Our antibody database is represented by more than 5,600 neuroscience products covering conditions ranging from Parkinson’s disease to bipolar disorder.

GABA (gamma-aminobutyric acid) plays a central role in neural research, as it is the major inhibitory neurotransmitter in the mammalian central nervous system (CNS). Disruption of GABA and its receptors have been expressed in a range of mental health conditions. A major study by Dr. Andrea Levinson et al has suggested an important role major depressive illness.

GABA acts by binding to receptor proteins at inhibitory pre and post-synaptic receptors. These receptors form two distinct classes:

GABA-B receptors are metabotropic receptors which produce long, slow responses. Changes in function of heterodimers GABA-B1 and GABA-B2 are implicated in a range of diseases, including multiple sclerosis. Recent research identified a functional homomeric GABA-B2 coupled to adenylyl cyclase, suggesting that the complexity of GABA-B2 function may be due to the presence of more than one receptor.

GABA-A/GABA-C receptors are ionotropic and have a fast inhibitory response. GABA-A has been widely studied, as the receptor is known to be targeted by a range of pharmaceutical compounds including anaesthetics, anticonvulsants and antidepressants. It is formed of three subunits, to which individual antibodies are targeted.

Dr. Levinson’s study revealed that sufferers of major depressive disorder have radically reduced levels of GABA in the brain. It was discovered that electro-convulsive therapy is effective because it resets GABA levels. Antibody research is now targeted on developing drugs that have the same effect, but in a more humane way.

We at Novus Biologicals have a vast number of products in our antibody catalogue, targeted at cancer research. They cover areas as diverse as apoptosis and cell signalling pathways, and antibodies include those derived from a number of tumour cell lines.

Now, it looks as if our cancer antibody database is set to expand once more. Scientists have recently uncovered exciting new facts on sarcomas – rare tumours affecting only a small minority of people, which are found in tissues throughout the body. Despite the rarity of sarcomas, the findings have enormous ramifications on the field of cancer therapy as a whole. They could pave the way for a whole catalogue of new treatments for the most common cancers affecting man.

Sarcomas are found in muscle, nerves, joint tissues, deep skin tissues and blood vessels. The proteins causing them undergo unique, well-characterised molecular changes which make them ideal models for the development of new cancer therapies. The findings have recently been made public at the 2010 ESMO conference on Sarcomas and Gastro-IntestinalStromal Tumours (GIST).

We at Novus Biologicals have over 130 antibody products targeted at sarcoma proteins which have been researched for a number of years. However, it has only been comparatively recently that novel treatments have started to emerge. Much of this is down to improvements in antibody assay techniques, enabling precise identification of protein mutations at a molecular level. The ESMO conference concentrated on the molecular alterations that occur in soft-tissue sarcomas, in particular GIST, and the development of treatments to combat them.

Antibody studies into human CHARGE syndrome have shown mutated CHD7 plays a major role in its development. CHARGE originates in neural crest cells (NCCs) during early embryonic development. It leads to a number of birth defects including craniofacial, heart, brain, urogenital, hearing and growth defects. New research conducted by Wysocka et al, of the Stamford University School of Medicine, indicates a connection with tumour development in adults.

Chromatin is the tightly-packed form of DNA found within the cell nucleus. It is controlled by a number of chromatin remodeler proteins, one of which is CHD7. CHD7 acts on nuclear proteins to allow activation or deactivation of various genes.

NCCs are unusual in that they migrate freely during embryonic development, differentiating into a range of cells including neural, heart, cartilage and bone cells. Wysocka et al, of the Stamford University School of Medicine, recently conducted antibody assays exploring the critical role CHD7 plays within neural crest cells.

Previous studies had showed mutated CHD7 was expressed in CHARGE cells. By blocking CHD7 release in tadpoles, cell migration was halted and symptoms similar to those of CHARGE sufferers were expressed, proving that uncorrupted CHD7 is essential to normal embryonic development.

Further antibody studies showed CHD7 worked in combination with the PBAF chromatin remodelling complex, to control remote genes. Previous studies have shown that Slug and Twist – two genes controlled by CHD7 and PBAF – are oncogenic.

We at Novus Biologicals have a number of proteins on our antibody database, which will help further research into this area.

The recently discovered FTO (Fat mass and obesity orientated) gene is of great interest to antibody research groups, throwing clearer insight into the reasons why some people have difficulty losing weight, even when following a healthy lifestyle.

Studies into serotonin (5-HT) are equally important, and its importance has been realised in a number of antibody studies into causes of weight gain. 5-HT receptors are located in the hypothalamus, which is a primary expression site for FTO. A number of research groups are currently looking at the way these two proteins may interact.

Recently, more than 70 obese volunteers signed up to a Sheffield sports centre to take part in a genetic study being conducted by the city’s Hallam University. The research, which started early in 2009 and is ongoing, looks at changes in participants’ motivation, compared to the levels of serotonin that is naturally released.

In vitro FTO antibody studies, using sera taken from human volunteers, have previously shown that higher levels of physical activity blocks the effects of the FTO gene. At the University of Maryland in 2008, researchers analysed activity levels against gene variants in a number of exercisers. They found the least FTO activity in those who were physically most active.

Serotonin, otherwise known as the ‘happy hormone’ has been shown to aid weight loss in a number of ways, including appetite suppression and motivation to energise. Therefore, it has an important role to play in blocking the release of FTO. We at Novus Biologicals have a wide range of FTO and serotonin antibodies on our antibody database, which will help to facilitate this research.