Thursday, May 14, 2009

Pancreatic Cancer HSP Trials

Pancreatic Cancer HSP trials began in 1997 for a Phase I study to involve fifteen patients through the Memorial Sloan-Kettering Cancer Center. HSP or heat-shock proteins are a of group proteins that are present in all cells. HSP are often identified during stressful situations such as extreme cold and hot conditions, and during deprivation of oxygen or glucose. Heat-shock proteins are often referred as the stress proteins.
Heat-shock proteins are the protein assistants of the cell. They have a library of every protein ever coded in the body. HSP understand the shape and the function of every amino acid sequence. If one amino acid sequence is not correct and a protein is not folded correctly the HSP is there to make sure that “neat and tidy” for the cell so the proteins are functioning at optimal level.
Heat-shock proteins are normally found inside the cell to help with protein functioning. If heat-shock proteins are found on the outside of the cell it means that the cell is not healthy.
When proteins are no longer useful the heat-shock proteins escort them to be dismantled by the cell into small amino acid pieces called peptides. The HSP then load the peptides onto another protein called major histocompatability complex (MHC). The fully loaded MHC takes the amino acid fragments (peptides) to the surface of the cell where the immune system is ready and waiting to react to the unfamiliar proteins.
When the cell dies it discharges the HSP and the peptide fragments of the extraneous protein. Circulating immune system dendritic cells or macrophages, referred to as antigen-presenting cells (APC), detect the HSP-peptide fragments. The HSP assist with loading the peptide fragments onto the CD91 receptor of the APC cell surface. The APC then swallow-up the HSP-peptide complexes. Once fully engulfed, the APC travel to the lymph nodes, the foundation of the immune system, where specialized immune cells called T- cells read the amino acid peptides sequences. The T-cells are able to code for a defense against that specific amino acid sequence. The T-cells are subsequently programmed to go through the body to seek out the specific foreign proteins and destroy the alien amino acid sequences. The T-cells are specific, being programmed to destroy the exact amino acid sequence that it was coded for and no other protein sequence.
When the body receives immunization with a sterile disease (vaccine) the body will recognize the disease-coded vaccine with the help of HSPs and the T-cells are activated and ready to fight off the disease. If the body is not immunized then the body has not built up a defensive system that is ready to combat the disorder.
Heat shock protein vaccines focus on individual vaccines specifically developed for each patient. Everybody has a detailed amino acid sequence in their cells that are explicitly coded for them. The HSP vaccine thus are “tailor-made” designer-drug style of vaccine to meet the specific requirements for each individual person.
Heat-shock proteins appear to work similar with cancer cells as with other diseases. Cancer can be removed from an individual and clinically weakened. The weakened cells can be injected back into the same patient. Heat-shock proteins keep track of every protein that is ever in the cell including abnormal proteins. If the weakened cells are injected into the body the heat-shock proteins will recognize that they are abnormal, bind against the abnormal proteins and bring to the surface of the cell. By bringing them to the surface the body’s immune systems recognizes an abnormal cell and builds up the defense. When a more powerful cancer occurs of that type the body’s immune systems is ready and quickly creates antibodies to counteract the abnormal proteins and removes the ailing cells.
With pancreatic cancer, the average survival rate is only 6 months by the time it is typically detected with only one in five patients surviving past one year.
During the 1997 pancreatic cancer HSP trials, the pancreatic enzymes began to degrade the HSPs. Only five of the 15 patients slated for the pancreatic cancer HSP trial could get the pancreatic cancer HSP vaccine. Due to the pancreatic enzymatic activity and the destruction of the heat-shock proteins, the trial was suspended. Of those five patients that were treated with the heat-shock protein procedure their survival rate was 8, 17, 30, 33, and 36 months after the procedure. The patient living for 36 months after the procedure did not have any signs of pancreatic cancer at the time. These five patients in the 1997 pancreatic cancer HSP study show very promising results in the heat-shock protein treatment technique. Since then, scientists have discovered a method to prevent pancreatic enzyme destruction of the heat-shock proteins. Study for Phase II pancreatic cancer HSP trials have been filled and are currently underway.


Improvement to cancer treatment is a continued challenge. Understanding the complexities of cancer and the treatment models are very critical. At http://www.scientificprinciple.org pancreatic cancer is a major focus.

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