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Add important lessons to your Custom Course, track your progress, and achieve your study goals faster. Proteomics technology is an approach of science to understand the expression of the whole set of proteins and its function at the cellular level.
Indeed, proteomics technology enables the researchers to look into the proteins level of the cancer cells, proteins being the physiological and pathological indispensible players.
Proteomics has the great potential to be one of the most powerful tools for cancer research. The pancreas is comprised of separate functional units that regulate two major physiological processes: digestion and glucose metabolism. Note the dramatic narrowing of the pancreatic duct associated with the poorly defined white neoplasm. Pancreatic ductal adenocarcinoma is a malignant tumor of epithelia originating in glandular tissue. The Figure 5 presents a schematic diagram of intracellular signalling pathways in pancreatic adenocarcinoma. Activated Kras engages a number of downstream effector pathways, including RAF–mitogen-activated protein kinase (RAFMAPK), phosphoinositide-3-kinase (PI3K), and RalGDS pathways (as shown in Figure 6) producing thus a remarkable array of cellular effects, including induction of proliferation, survival and invasion through the stimulation of several effector pathways. Lauth M, Toftgard R and al (2010) “DYRK1B-dependent autocrine-to-paracrine shift of Hedgehog signaling by mutant RAS” Nat.
Indeed, one major issue in pancreas cancer is the insensitivity to treatment due to the activation of defense systems, notably those producing antioxydants in which Mirk acts. The ProteoLux® Pro system enable to degrade specifically one or more proteins expressed in vivo at a given time and in a given cell type. The ProteoLux® Pro system also enables you to control the concentration of a protein according to the lighting alternation between far red light and red light. The ProteoLux® Pro system : an amazing tool to study every overexpressed protein, notably oncoproteins. Indeed, oncogenes which code for oncoproteins are mutated proto-oncogenes, very important genes involved in the regulation of cell cycle, cell growth and cell proliferation.
The potency of Mirk as a therapeutic target can easily and relatively fastly be studied with the ProteoLux® system. Besides, by using several intrabodies it is possible to target several proteins at the same time. As shown in Figure 4, tumors possess cytogenetically different clones corresponding to different stages of progression of the disease. The discovery and understanding of the altered genes causing cancer (oncogenes, tumor-suppressor genes, and microRNA genes) and of the pathways involved permit the development of cancer therapies. The ProteoLux® system can interest big pharmaceutical firms like Roche or Novartis which are already focusing on pancreatic cancer. Large food molecules (for example, proteins, lipids, nucleic acids, and starches) must be broken down into subunits that are small enough to be absorbed by the lining of the alimentary canal.
In the small intestine, pancreatic amylase does the ‘heavy lifting’ for starch and carbohydrate digestion ([link]).
The digestion of protein starts in the stomach, where HCl and pepsin break proteins into smaller polypeptides, which then travel to the small intestine ([link]). The three lipases responsible for lipid digestion are lingual lipase, gastric lipase, and pancreatic lipase. The mechanical and digestive processes have one goal: to convert food into molecules small enough to be absorbed by the epithelial cells of the intestinal villi.
Absorption can occur through five mechanisms: (1) active transport, (2) passive diffusion, (3) facilitated diffusion, (4) co-transport (or secondary active transport), and (5) endocytosis.
Because the cell’s plasma membrane is made up of hydrophobic phospholipids, water-soluble nutrients must use transport molecules embedded in the membrane to enter cells. In contrast to the water-soluble nutrients, lipid-soluble nutrients can diffuse through the plasma membrane. Active transport mechanisms, primarily in the duodenum and jejunum, absorb most proteins as their breakdown products, amino acids. The large and hydrophobic long-chain fatty acids and monoacylglycerides are not so easily suspended in the watery intestinal chyme. The free fatty acids and monoacylglycerides that enter the epithelial cells are reincorporated into triglycerides. The products of nucleic acid digestion—pentose sugars, nitrogenous bases, and phosphate ions—are transported by carriers across the villus epithelium via active transport. The electrolytes absorbed by the small intestine are from both GI secretions and ingested foods.
In general, all minerals that enter the intestine are absorbed, whether you need them or not.
Iron—The ionic iron needed for the production of hemoglobin is absorbed into mucosal cells via active transport. Bile salts and lecithin can emulsify large lipid globules because they are amphipathic; they have a nonpolar (hydrophobic) region that attaches to the large fat molecules as well as a polar (hydrophilic) region that interacts with the watery chime in the intestine. Intrinsic factor secreted in the stomach binds to the large B12 compound, creating a combination that can bind to mucosal receptors in the ileum. The surgeons at University Surgeons Associates, PC are experienced in using surgical techniques to treat problems of the gastrointestinal tract. Each year, a number surgical procedures are performed in the United States to treat diseases of the intestines. Preoperative preparation includes blood work, medical evaluation, chest x-ray and an EKG depending on your age and medical condition. After your surgeon reviews with you the potential risks and benefits of the operation, you will need to provide written consent for surgery. Drugs such as aspirin, blood thinners, anti-inflammatory medications (arthritis medications) and Vitamin E will need to be stopped temporarily for several days to a week prior to surgery.
You will probably be able to get back to most of your normal activities in two to three weeks time. In this lesson, you will learn about the enzymes found in pancreatic juice that allow your body to break down carbohydrates, proteins and fats. Different kinds of pancreatic cancer exist : Adenocarcinomas, which represents 95% of cases, adenosquamous carcinomas, singet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas and undifferentiated carcinomas with osteoclast-like giant cells which represent the remaining 5%. This cancer causes the death of thousands people in the world each year of whom 7000 French and 36 800 American. The 5- year survival rate of all patients is below 5%, and the median survival time after diagnosis is 6 months.
Other recognized precursor lesions of adenocarcinoma (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) likely harbor a distinct compendium of genetic alterations in their path to invasive cancer. KRAS encodes a member of the RAS family of guanosine triphosphate (GTP)-binding proteins that mediate a range of cellular functions, including proliferation, cell survival, cytoskeletal remodeling, and motility, among others. Either single-agent or combination therapies with farnesyl transferase inhibitors (SWOG 9924 study) that target Ras translocation have shown limited activity. It is expressed at low levels in most normal tissues but at elevated levels in quiescent pancreatic cancer cells. By inhibiting Mirk, the protection of cancer cells will be inhibited, making them more sensitive to actual treatment (chemotherapy, radiotherapy…).


The ProteoLux® Pro system also enables you to degrade specifically muted protein (not the normal one) by using specific intrabodies.
This heterogeneity contributes to differences in clinical behavior and responses to treatment of tumors of the same diagnostic type.
Indeed, Roche has developed a molecule for chemotherapy, Traceva and Novartis has created a new product Afinitor, which permit also to increase life expectancy of people affect by pancreatic endocrine tumor. It is the cancer-focused technology development and commercialisation arm of Cancer Research UK, the world’s largest cancer charity.
Glucose, galactose, and fructose are the three monosaccharides that are commonly consumed and are readily absorbed.
After amylases break down starch into smaller fragments, the brush border enzyme ?-dextrinase starts working on ?-dextrin, breaking off one glucose unit at a time. Chemical digestion in the small intestine is continued by pancreatic enzymes, including chymotrypsin and trypsin, each of which act on specific bonds in amino acid sequences. The most common dietary lipids are triglycerides, which are made up of a glycerol molecule bound to three fatty acid chains.
However, because the pancreas is the only consequential source of lipase, virtually all lipid digestion occurs in the small intestine. Two types of pancreatic nuclease are responsible for their digestion: deoxyribonuclease, which digests DNA, and ribonuclease, which digests RNA.
As you will recall from Chapter 3, active transport refers to the movement of a substance across a cell membrane going from an area of lower concentration to an area of higher concentration (up the concentration gradient). Moreover, substances cannot pass between the epithelial cells of the intestinal mucosa because these cells are bound together by tight junctions. Once inside the cell, they are packaged for transport via the base of the cell and then enter the lacteals of the villi to be transported by lymphatic vessels to the systemic circulation via the thoracic duct. The small intestine is highly efficient at this, absorbing monosaccharides at an estimated rate of 120 grams per hour. Bile salts not only speed up lipid digestion, they are also essential to the absorption of the end products of lipid digestion. However, bile salts and lecithin resolve this issue by enclosing them in a micelle, which is a tiny sphere with polar (hydrophilic) ends facing the watery environment and hydrophobic tails turned to the interior, creating a receptive environment for the long-chain fatty acids. The triglycerides are mixed with phospholipids and cholesterol, and surrounded with a protein coat.
Since electrolytes dissociate into ions in water, most are absorbed via active transport throughout the entire small intestine.
Once inside mucosal cells, ionic iron binds to the protein ferritin, creating iron-ferritin complexes that store iron until needed.
When blood levels of ionic calcium drop, parathyroid hormone (PTH) secreted by the parathyroid glands stimulates the release of calcium ions from bone matrices and increases the reabsorption of calcium by the kidneys. Fat-soluble vitamins (A, D, E, and K) are absorbed along with dietary lipids in micelles via simple diffusion. Chemical digestion breaks large food molecules down into their chemical building blocks, which can then be absorbed through the intestinal wall and into the general circulation. We participate regularly in the multidisciplinary GI conference and Tumor conference which review imaging, endoscopic findings and biopsies with the gastroenterologists, radiologists and pathologists. These activities include showering, driving, walking up stairs, light exercise and even working. Consulting Medline reveals that, since 1997, when the word proteomics first appeared as an entry, approx. However, currently only around 500 out of the estimated >3000 proteins that are predicted to be druggable are exploited. The acinar cells produce digestive enzymes and constitute the bulk of the pancreatic tissue. Aggressive and devastating disease, it is one of the most common causes of cancer related death. Activating mutations impair the intrinsic GTPase activity of the KRAS gene product, resulting in a protein that is constitutively active in intracellular signal transduction.
Our system permits these companies to broaden their scope against pancreatic cancer by studying easily the potency of a new target.
Chemical digestion, on the other hand, is a complex process that reduces food into its chemical building blocks, which are then absorbed to nourish the cells of the body ([link]). At the same time, the cells of the brush border secrete enzymes such as aminopeptidase and dipeptidase, which further break down peptide chains. Pancreatic lipase breaks down each triglyceride into two free fatty acids and a monoglyceride. The nucleotides produced by this digestion are further broken down by two intestinal brush border enzymes (nucleosidase and phosphatase) into pentoses, phosphates, and nitrogenous bases, which can be absorbed through the alimentary canal wall.
Each day, the alimentary canal processes up to 10 liters of food, liquids, and GI secretions, yet less than one liter enters the large intestine. In this type of transport, proteins within the cell membrane act as “pumps,” using cellular energy (ATP) to move the substance.
Thus, substances can only enter blood capillaries by passing through the apical surfaces of epithelial cells and into the interstitial fluid.
The absorption of most nutrients through the mucosa of the intestinal villi requires active transport fueled by ATP. All normally digested dietary carbohydrates are absorbed; indigestible fibers are eliminated in the feces. Short-chain fatty acids are relatively water soluble and can enter the absorptive cells (enterocytes) directly. During absorption, co-transport mechanisms result in the accumulation of sodium ions inside the cells, whereas anti-port mechanisms reduce the potassium ion concentration inside the cells. When the body has enough iron, most of the stored iron is lost when worn-out epithelial cells slough off.
PTH also upregulates the activation of vitamin D in the kidney, which then facilitates intestinal calcium ion absorption. This is why you are advised to eat some fatty foods when you take fat-soluble vitamin supplements. Intestinal brush border enzymes and pancreatic enzymes are responsible for the majority of chemical digestion. With the help of bile salts and lecithin, the dietary fats are emulsified to form micelles, which can carry the fat particles to the surface of the enterocytes.
We utilize laparoscopic and open techniques to treat tumors, bleeding, reflux, obstruction, foreign bodies and inflammation of the bowel. These tests allow the surgeon to look inside of the gastrointestinal system and may be useful.  Prior to the operation, other blood tests, electrocardiogram (EKG) or a chest x-ray might be required. The multiple targets of the system and its advantages will be exemplified in the case of the pancreatic ductal adenocarcinoma (PDAC), a major unsolved health problem. In fact this gland permits to produce hormones like insulin and to secrete digestive enzymes contained in a pancreatic juice which are inserted into the small intestine to help for assimilation of nutrients. They are organized into grape-like clusters that are at the smallest termini of the branching duct system.
It is characterized by invasiveness, rapid progression and profound resistance to treatment.


Other established risk factors include diets high in meats and fat, low serum folate levels, obesity, long-standing diabetes mellitus, and chronic pancreatitis.
But surgery may only be used if the tumor is not too advanced and if the cancer does not present metastasis.
In addition to its role in pancreatic cancer initiation, constitutive RAS signaling appears to be required for pancreatic cancer maintenance as well.
Mirk appears not to be an essential gene for normal cells from embryonic knockout studies in mice and RNA interference studies on cultured cells.
Notably, they will be able to develop cancer stage-specific drugs basing on the ProteoLux® system. In this section, you will look more closely at the processes of chemical digestion and absorption.
Your bodies do not produce enzymes that can break down most fibrous polysaccharides, such as cellulose.
The fatty acids include both short-chain (less than 10 to 12 carbons) and long-chain fatty acids. Almost all ingested food, 80 percent of electrolytes, and 90 percent of water are absorbed in the small intestine. Passive diffusion refers to the movement of substances from an area of higher concentration to an area of lower concentration, while facilitated diffusion refers to the movement of substances from an area of higher to an area of lower concentration using a carrier protein in the cell membrane.
Water-soluble nutrients enter the capillary blood in the villi and travel to the liver via the hepatic portal vein. The monosaccharides glucose and galactose are transported into the epithelial cells by common protein carriers via secondary active transport (that is, co-transport with sodium ions). Despite being hydrophobic, the small size of short-chain fatty acids enables them to be absorbed by enterocytes via simple diffusion, and then take the same path as monosaccharides and amino acids into the blood capillary of a villus.
Without micelles, lipids would sit on the surface of chyme and never come in contact with the absorptive surfaces of the epithelial cells. After being processed by the Golgi apparatus, chylomicrons are released from the cell ([link]). To restore the sodium-potassium gradient across the cell membrane, a sodium-potassium pump requiring ATP pumps sodium out and potassium in. When the body needs iron because, for example, it is lost during acute or chronic bleeding, there is increased uptake of iron from the intestine and accelerated release of iron into the bloodstream.
Most water-soluble vitamins (including most B vitamins and vitamin C) also are absorbed by simple diffusion. Water absorption is driven by the concentration gradient of the water: The concentration of water is higher in chyme than it is in epithelial cells. Comparing this frequency with the occurrence of the search string ‘genomics’ in 0.17% of the cancer literature, it becomes obvious that proteomics has attracted major scientific attention in the field of cancer research.
The ducts, which add mucous and bicarbonate to the enzyme mixture, form a network of increasing size, culminating in main and accessory pancreatic ducts that empty into the duodenum.
Pain in the abdomen, loss of appetite and so loss of weight, painless jaundice, diabetes mellitus or elevated blood sugar level, trousseau sign or clinical depression are common symptoms of pancreatic cancer. This surgery is not easy because of the high amount of veins surrounding the pancreas and this operation is possible only in 20% of cases. While indigestible polysaccharides do not provide any nutritional value, they do provide dietary fiber, which helps propel food through the alimentary canal. Although the entire small intestine is involved in the absorption of water and lipids, most absorption of carbohydrates and proteins occurs in the jejunum.
Co-transport uses the movement of one molecule through the membrane from higher to lower concentration to power the movement of another from lower to higher. The monosaccharides leave these cells via facilitated diffusion and enter the capillaries through intercellular clefts.
Short chains of two amino acids (dipeptides) or three amino acids (tripeptides) are also transported actively.
Too big to pass through the basement membranes of blood capillaries, chylomicrons instead enter the large pores of lacteals.
Since women experience significant iron loss during menstruation, they have around four times as many iron transport proteins in their intestinal epithelial cells as do men.
The fats are then reassembled into triglycerides and mixed with other lipids and proteins into chylomicrons that can pass into lacteals. Vice versa, a search for ‘cancer AND proteomics’ shows that 16% of the proteomics literature deals with cancer, testifying that the attraction is mutual. The endocrine pancreas, consisting of four specialized cell types that are organized into compact islets embedded within acinar tissue, secretes hormones into the bloodstream. This is the case for 5 to 10% of patient but the gene responsible of this disease is not yet identified.
Finally, endocytosis is a transportation process in which the cell membrane engulfs material. The monosaccharide fructose (which is in fruit) is absorbed and transported by facilitated diffusion alone. However, after they enter the absorptive epithelial cells, they are broken down into their amino acids before leaving the cell and entering the capillary blood via diffusion.
Intrinsic factor secreted in the stomach binds to vitamin B12, preventing its digestion and creating a complex that binds to mucosal receptors in the terminal ileum, where it is taken up by endocytosis. Other absorbed monomers travel from blood capillaries in the villus to the hepatic portal vein and then to the liver.
The ?- and ?-cells regulate the usage of glucose through the production of glucagon and insulin, respectively. Furthermore for the moment there are no real guidelines for preventing from pancreatic cancer.
By the time chyme passes from the ileum into the large intestine, it is essentially indigestible food residue (mainly plant fibers like cellulose), some water, and millions of bacteria ([link]). The monosaccharides combine with the transport proteins immediately after the disaccharides are broken down. The chylomicrons are transported in the lymphatic vessels and empty through the thoracic duct into the subclavian vein of the circulatory system. Pancreatic polypeptide and somatostatin that are produced in the PP and ?-cells modulate the secretory properties of the other pancreatic cell types. For those who cannot undergo this surgery their median survey is approximately of 6 months. Once in the bloodstream, the enzyme lipoprotein lipase breaks down the triglycerides of the chylomicrons into free fatty acids and glycerol.
These breakdown products then pass through capillary walls to be used for energy by cells or stored in adipose tissue as fat. Liver cells combine the remaining chylomicron remnants with proteins, forming lipoproteins that transport cholesterol in the blood. Nevertheless, PDAC is insensitive to most therapies including chemotherapy, radiotherapy and immunotherapy.



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