Celiac Disease
Celiac Disease is an auto-immune system that may occur in genetically predisposed people where the ingestion of gluten results in the damage of the small intestine. Specifically the damage on the small intestines happens to the villi, which are small finger like outgrowths that line the small intestine that help nutrient absorption, therefore due to this disease people are unable to absorb nutrients properly if gluten is ingested. It is generally estimated that 1 out of every 100 people in the world are affected by this disease, although most people are left undiagnosed due to its specificity. Something also important about this disease is the fact that is it hereditary, meaning if relatives have this disease your likelihood of obtaining is increased.
Symptoms:
-Digestive problems (things like bloating, pain, gas, diarrhea, weight loss, pale stool, etc.)
-Severe skin rash known as dermatitis herpetiformis
-Iron deficiency anemia (low blood count)
-Musculoskeletal problems (muscle cramps bone and joint pain)
Long Term affects of this disease are:
-Iron deficiency anemia
-Pancreatic insufficiency
-Lactose intolerance
-Gall bladder malfunction
-Infertility and miscarriages
-Vitamin and mineral deficiencies
-Intestinal lymphomas
-Neurological manifestations
-Early onset osteoporosis and osteopenia
- Central and peripheral nervous system disorders
Which pathway is defective?
PPAR (Peroxisome Proliferator-Activated Receptors) signaling pathway: It was concluded in a study that the down-regulation of proteins involved in the PPAR signaling were highly associated with the cause of Celiac disease. The study analyzed the intestinal mucosa proteome alterations using two dimensional difference gel electrophoresis, they tested Celiac Disease patients of varying degrees of histological abnormalities defined by Marsh criteria and controls (Stanford experiment from the school of medicine). There was basically two groups of patients, those with Type 0-I of Celiac Disease known as Group A and the other patients were group B, with Types II-III Celiac Disease. It resulted that in Group B there were many down-regulated proteins that were directly implicated in the peroxisome proliferator-activated receptor signaling pathway. This signal pathways was defective due to the fact that the deregulation of those proteins occurred in apoptosis/survival pathways, which resulted in more severe tissue damage in Group B patients.Meaning that there was no a destruction of the cell, therefore creating a defect in the signaling pathway. Furthermore, the studies also showed that IgMs( antibodies) were found to be very strongly increased in Group B, illustrating that more antibodies were needed because something went wrong in the signaling pathway.
The Experimental Drug: NVP-BEZ235
The experimental drug NVP-BEZ235 is being tested in the laboratory at University of California, Los Angeles and has shown that this drug blocks two crucial cancer cell signaling pathways that inhibits the growth of ovarian cells. This is an extremely important drug because it could potentially be used after chemotherapy and all sort of other conventional treatments are not working to reduce the size of ovarian cancer cells. It is able to re-sensitize the ability of the cells to work through these therapies.
Doctors have become very hopeful of this drug, as exemplified below:
"We were very encourage to find that NPV-BEZ235 could re-sensitize the ovarian cancer cells to standard platinum treatment," Dorgio said. "In addition, we found this drug to be more effective in inhibiting ovarian cancer cell growth than other drugs that target only one checkpoint, mTOR, in this pathway. We believe that NVP-BEZ235 has superior efficacy because of the dual effect on P13Kinase and mTOR."
Only the structural form of this drug is available at this point.
This new found drug has been experimented throughout various diseases and has proved to have great results in other inhibition of signaling pathways. It is said that this drug is a novel and potent dual P13Kinase/mTOR inhibitor that is currently in phase of 1/2 clinical trials for advanced solid tumors. It is able to inhibit ATM and DNA-PKcs, two of the major kinases responding to ionization radiation- induced DNA double stand breaks, therefore has potential to act as an effective radiosensitizer for GBMs in the clinic. Overall the idea of this drug brings great results in the area regarding cancer, it sparks a hope for future advancements in the field of cancer research and treatment.
The experimental drug NVP-BEZ235 is being tested in the laboratory at University of California, Los Angeles and has shown that this drug blocks two crucial cancer cell signaling pathways that inhibits the growth of ovarian cells. This is an extremely important drug because it could potentially be used after chemotherapy and all sort of other conventional treatments are not working to reduce the size of ovarian cancer cells. It is able to re-sensitize the ability of the cells to work through these therapies.
Doctors have become very hopeful of this drug, as exemplified below:
"We were very encourage to find that NPV-BEZ235 could re-sensitize the ovarian cancer cells to standard platinum treatment," Dorgio said. "In addition, we found this drug to be more effective in inhibiting ovarian cancer cell growth than other drugs that target only one checkpoint, mTOR, in this pathway. We believe that NVP-BEZ235 has superior efficacy because of the dual effect on P13Kinase and mTOR."
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| Only the structural form of this drug is available at this point. This new found drug has been experimented throughout various diseases and has proved to have great results in other inhibition of signaling pathways. It is said that this drug is a novel and potent dual P13Kinase/mTOR inhibitor that is currently in phase of 1/2 clinical trials for advanced solid tumors. It is able to inhibit ATM and DNA-PKcs, two of the major kinases responding to ionization radiation- induced DNA double stand breaks, therefore has potential to act as an effective radiosensitizer for GBMs in the clinic. Overall the idea of this drug brings great results in the area regarding cancer, it sparks a hope for future advancements in the field of cancer research and treatment. |
Works Cited
Ferretti, Gianna, Tiziana Bacchetti, Simona Masciangelo, and Letizia Saturni. "Celiac Disease, Inflammation and Oxidative Damage: A Nutrigenetic Approach." Nutrients 4.12 (2012): 243-57. Web.
Mukherjee, B., N. Tomimatsu, K. Amancherla, C. Camacho, and S. Burma. "Abstract 3745: The Dual PI3K/mTOR Inhibitor NVP-BEZ235 Is a Potent Inhibitor of ATM- and DNA-PKcs-mediated DNA Damage Responses." Cancer Research 72.8 Supplement (2012): 3745. Web.
Simula, Maria P., Renato Cannizzaro, Vincenzo Canzonieri, Alessandro Pavan, Stefania Maiero, Giuseppe Toffolio, and Valli De Re. "PPAR Signaling Pathway and Cancer-Related Proteins Are Involved in Celiac Disease-Associated Tissue Damage." Molecular Medicine. NCBI, 3 Mar. 2012. Web. 9 Nov. 2014.
Sollid, Ludvig M., and Chaitan Khosla. "Future Therapeutic Options for Celiac Disease." Nature Clinical Practice Gastroenterology & Hepatology 2.3 (2005): 140-47. Web.
University of California - Los Angeles Health Sciences. "Experimental Drug Inhibits Cell Signaling Pathway and Slows Ovarian Cancer Growth." ScienceDaily. ScienceDaily, 18 Apr. 2011. Web. 10 Nov. 2014.
"What Is Celiac Disease? - Celiac Disease Foundation." Celiac Disease Foundation. Celiac Disease Foundation, May 2013. Web. 09 Nov. 2014.
