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25-04-2010, 08:42 PM



The present study NEW DRUG DESIGN FOR BLOOD CANCER THROUGH PENTOSTATIN MODIFICATION STUDIES was conducted in Aravinda Biosolution Pvt.Ltd. Narayanaguda,Hyderabad(A.P) between April 2009 to may 2009 with following Aims and Objectives:-
To make more active drug.
To learn the instrumentation and technique.
Cancer is caused by an abnormal overgrowth of cells with more than 100 cancer subtypes depending on which cell grows. In many cancers, the cells clump together to form solid tumors, but in some the cells are dispersed around the blood stream (leukemia) or the lymphatic system (lymphoma). Prognosis of cancer has improved greatly in modern times owing to treatment advances and early detection programs. However, although survival rates have improved, cancer still remains the 2nd top cause of death, second only to heart disease in the USA. Misdiagnosis of cancer is naturally possible but not common if professional medical advice is sought, because physicians will usually perform comprehensive diagnostic testing if cancer is a possibility. Diagnostic tests have also improved in accuracy including newer tumor marker blood tests. Self-diagnosis of cancer is usually incorrect and quite common is for people to fear that they have cancer based on a symptom (e.g. weight loss, persistent cough, lumps, or Cancer of one or more of the components of blood. Lymphoma, leukemia and multiple myeloma are the main forms of blood cancer. Blood cancers are more common in adults than in children¦
Blood cancer or Leukemia is a disease of unknown cause where the bone marrow produces large numbers of abnormal cells. This means that the normal marrow is pushed into smaller and smaller areas, which results in fewer cells being produced and leads to some of the symptoms listed below.
There are many types of leukemia and each of them is classified according to the exact cell type affected by the disease.
Chronic leukemia is a slowly progressive form of leukemia and tends to involve more mature cell types.
Acute leukemia is rapidly progressive if not treated and involves more immature cells. It develops rapidly from the earliest forms of cells in the immature bone marrow cells (blasts). It requires urgent medical treatment but is generally responsive to chemotherapy.
Acute leukemia is a rare disease that is more common in children and young people. However, their survival rate is better than in older people.
Leukemia are grouped by how quickly the disease develops as well as by the type of white blood cell that is affected. The two main types of leukemia are acute and chronic. Acute leukemia is a rapidly progressing disease that affects immature blood cells (blasts) which are not yet fully developed. These blasts cannot carry out their normal functions, increases quickly and the disease gets worse quickly. Acute leukemia tends to affect younger people. In chronic leukemia, some blast cells are present, but they are more mature and can carry out some of their normal functions. The number of blasts increases less rapidly than in acute leukemia and therefore the disease gets worse slowly.Leukemia can arise in either of the two main types of white blood cells: lymphoid cells or myeloid cells. Leukemia that affects lymphoid cells is called lymphocytic leukemia and myeloid cells are called myeloid or myelogenous leukemia.
The most common types of leukemia are :
Acute Myelogenous Leukemia (AML)
Found in both adults and children. AML is also called acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia, and acute nonlymphocytic leukemia. There are different subtypes of AML based on how mature (developed) the cancer cells are at the time of diagnosis and how different they are from normal cells
Acute Lymphocytic Leukemia (ALL)
The most common type in young children under 19 years. Also affects adults of 65years and older.
Chronic Myelogenous Leukemia (CML) Affect mainly in adults
Chronic Lymphocytic Leukemia (CLL) Occurs in adults over 55 years. It almost never affects children
Leukemia development
The four types of leukemia each begin in a cell in the bone marrow. The cell undergoes a leukemic change and it multiplies into many cells. The leukemia cells grow and survive better than normal cells and, over time, they crowd out normal cells. Normal stem cells in the marrow form three main cell-types: Red cells, platelets and white cells. There are two major types of white cells: germ-ingesting cells (neutrophils and monocytes) and lymphocytes, which are part of the body's immune system and help to fight to infection.The rate at which leukemia progresses and how the cells replace the normal blood and marrow cells are different with each type of leukemia.
Acute Leukemia
In acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL), the original acute leukemia cell goes on to form about a trillion more leukemia cells. These cells are described as "nonfunctional" because they do not work like normal cells. They also crowd out the normal cells in the marrow; in turn, this causes a decrease in the number of new normal cells made in the marrow. This further results in low red cell counts (anemia). The lack of normal white cells impairs the body's ability to fight infections. A shortage of platelets results in bruising and easy bleeding.
Chronic Leukemia
In chronic myelogenous leukemia (CML), the leukemia cell that starts the disease makes blood cells (red cells, white cells and platelets) that function almost like normal cells. The number of red cells is usually less than normal, resulting in anemia. But many white cells and sometimes many platelets are still made. Even though the white cells are nearly normal in how they work, their counts are high and continue to rise. This can cause serious problems if the patient does not get treatment. If untreated, the white cell count can rise so high that blood flow slows down and anemia becomes severe.In chronic lymphocytic leukemia (CLL), the leukemia cell that starts the disease makes too many lymphocytes that do not function. These cells replace normal cells in the marrow and lymph nodes. They interfere with the work of normal lymphocytes, which weakens the patient's immune response. The high number of leukemia cells in the marrow may crowd out normal blood-forming cells and lead to a low red cell count (anemia). A very high number of leukemia cells building up in the marrow also can lead to low neutrophil and platelet counts.Unlike the other three types of leukemia, some patients with CLL may have disease that does not progress for a long time. Some people with CLL have such slight changes that they remain in good health and do not need treatment for long periods of time. Most patients require treatment at the time of diagnosis or soon after.
List of symptoms of Blood cancer:
The list of signs and symptoms mentioned in various sources for Blood cancer includes the 22 symptoms listed below:
Fatigue -It means lacking energy or strength and is a very common symptom. However, the term in common usage may mean many things, including drowsiness (sleepiness), lethargy, tiredness, malaise, listlessness, or weakness (including muscular weakness).
Malaise -General feelings of discomfort or being ill-at-ease. See free access online books about Malaise below. See detailed information below for a list of 253 causes of Malaise, including diseases and drug side effect causes.
Breathlessness -Breathing difficulty of any kind (or any kind of "shortness of breath") is a potentially life-threatening emergency. It can indicate numerous dangerous causes such as heart attack, pneumonia, or pulmonary embolism. There are other less serious causes, but these highly dangerous conditions need to be considered. Refer to the causes of breathing difficulty or causes of chest pain. These symptoms need to be diagnosed immediately by a medical professional because they can represent a life-threatening emergency.
Weakness -Further information about Weakness is below, or review more specific information about these types of Weakness: arm weakness, facial weakness, hand weakness, leg weakness, muscle weakness, back weakness, progressive weakness, motor weakness or refer to muscular weakness of a body area or entire body weakness. General weakness may also be caused by fatigue, drowsiness, prostration, syncope (fainting), or malaise. For inability to move a body part, see paralysis. For weakness related to exercise or exertion, see exercise symptoms. Weakness may also occur due to numbness or paresthesias in the affected area. Any type of weakness is a serious symptom requiring prompt professional medical advice.
Excessive or easy bruising
Bleeding gums or frequent nose bleeds -Abnormal bleeding from the gums may be mostly due to nutritional deficiencies or blood dyscrasias. Recurrent infections or fever
Sweating at night -Sweating during the night (usually a cold sweat).
Weight loss -Loss of body weight can occur due to various conditions ranging from undereating, eating disorders, to severe metabolic conditions including diabetes. Infant weight loss is often classed as failure to thrive. For inadequate growth without weight loss see poor growth..
Anorexia -This is known as a lack of or loss of appetite for food.
Lymph node (gland) enlargement
Lumps or abdominal distension due to enlarged abdominal organs
Abdominal pain -Further information about Abdominal pain is below, or review more specific information about these types of Abdominal pain: stomach cramps, stomach ache, abdominal discomfort, abdominal tenderness, heartburn, upper abdominal pain, kidney pain, bellyache or other types.
Abdominal pain causes can range from extremely severe life-threatening conditions (e.g. acute appendicitis, abdominal aneurysm), to various less serious conditions (e.g., heartburn, reflux, gastroenteritis, etc.) Any symptom of abdominal pain needs prompt professional medical advice. Sudden and/or very severe abdominal pain should be treated as a medical emergency. It is often helpful to categorize abdominal pain into more specific types such as lower abdominal pain, upper abdominal pain, left abdominal pain, right abdominal pain, epigastric pain (pain behind the breastbone, such as in heartburn, reflux, or GERD), side pain, and other types of abdominal pain. Abdominal pain is a very common symptom, and also common in children. Unfortunately, because there are so many possible causes of abdominal pain, and many cases are not serious, many cases of acute appendicitis are misdiagnosed each year as gastroenteritis or some other similar condition, especially in children and infants. Although appendicitis is an uncommon condition, it can be fatal. And there are many other serious conditions that may cause abdominal pain.
Bone pain -Pain affecting the bones.
Back pain-Pain in the back region.
Bone fractures from minimal trauma-Breakage of bones. See free access online books about Fractures below.
Confusion -Mental confusion and impaired thinking.
Delirium -Further information about Delirium is below, or review more specific information about these types of Delirium: delirium tremens, Level of consciousness, decreased, Unresponsiveness, Reduced alertness or other types.
A person with delirium has little in the way of rational consciousness. There is no ability to carry on a conversation in any coherent manner, and indeed a delirious person may not even know you are there. True delirium needs to be distinguished from other symptoms such as dementia, delusions, hallucinations, psychosis or dissociation symptoms.
The possible causes of a headache range from a relatively harmless common headache or common cold to life-threatening emergencies like meningitis or even the unlikely occurrence of a brain tumor. Various types of headache are possible: common headache, migraine, cluster headache, sexual headache, or other types of headache. Any incident of head injury (i.e. brain injury), even in the past, raises the possibility of concussion or other results of head injury. Headache also commonly occurs with various diseases that also cause fever, of which there are numerous possibilities; see causes of fever. Prompt medical attention for diagnosis and treatment is advisable for any headache.
Visual disturbance -Any disturbance to ones vision.
Fluid retention - A condition where a person retains fluid usually causing oedema.
Decreased urination
To find the cause of symptoms, the physician reviews the patient's personal and family medical history and perform a physical examination. In addition to checking general signs of health, the doctor checks for enlargement in the liver, spleen, lymph nodes under the arms, groin, and neck. The doctor also may order laboratory tests, especially blood test that helps in the diagnosis of leukemia. Blood, drawn from a vein is examined under a microscope to determine the level of blood cell counts (i.e. the number of mature cells and blasts). The test also include the examining of blood for signs that leukemia has affected the liver and kidneys. Blood test disclose leukemia but to confirm, biopsy (removal of tissue to look for cancer cells) is performed in which a sample of bone marrow is examined by a hematologist, oncologist or pathologist. Samples of both liquid (aspirate) and solid bone marrow (biopsy) are taken, usually from a hip bone. In bone marrow aspiration, the doctor withdraws the sample by inserting a needle into a large bone (usually the hip) and removing a small amount of liquid bone marrow. In bone marrow biopsy, the doctor uses a very thick needle to remove a small piece of bone and bone marrow. If leukemia cells are found in the bone marrow sample, further tests are performed to find the extent of the disease. These include:
Cytogenetic Examination:
Cytogenetic examination of tissue is the method of analyzing the number and shape of the chromosomes or gene abnormalities in the cells. This is very helpful in diagnosing specific types of leukemia and in determining the treatment.
Immunophenotyping :
This laboratory test is used identify specific type of cell, in a sample of blood cells, marrow cells, or lymph node cells, based on the types of antigens or markers on the surface of the cell. This process is used to diagnose the subtype of AML by comparing the cancer cells to normal cells of the immune system.If leukemia has been diagnosed the following tests may be done to determine if the cancer has spread to other parts of the body.
Spinal tap or Lumbar puncture (LP) :
Spinal tap checks for leukemia cells in the fluid that fills the spaces in and around the brain and spinal cord (cerebrospinal fluid). The collection of leukemia cells in the central nervous system can affect mental processes. The physician uses a long, thin needle to remove fluid from the spinal column. The needle is inserted in between the bones in the spine following a small injection into the skin over the injection site in order to minimize discomfort.
Chest x-rays :
A chest x-ray film of the organs and bones inside the chest is frequently taken to look for signs of infection or lymph node involvement by leukemia.
Ultrasound Scan:
A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs in the abdomen and make echoes. The echoes form a picture of body tissues called a sonogram.
Spinal tap”The doctor removes some of the cerebrospinal fluid (the fluid that fills the spaces in and around the brain and spinal cord). The doctor uses a long, thin needle to remove fluid from the spinal column. The procedure takes about 30 minutes and is performed with local anesthesia. The patient must lie flat for several hours afterward to keep from getting a headache. The lab checks the fluid for leukemia cells or other signs of problems.
Because leukemia starts in the bone marrow and often has spread to other organs by the time it is detected, there is no need for traditional staging. All leukemia are classified according to their genotypes, or their unique chromosomal arrangements, which also enables the physicians to determine risk factorsAcute leukemia is classified in the French- American- British (FAB) system based upon the microscopic appearance of leukemia cells. According to FAB classification, acute leukemia is divided into eight subtypes of acute myelogenous leukemia (AML) and three subtypes of acute lymphocytic leukemia (ALL).Chronic lymphocytic leukemia (CLL) is classified by 2 different staging systems, known as RAI Classification and Binet Staging, both based on the parts of the body affected by the leukemia.
The main features of Rai Classification stage of the chronic lymphocytic leukemia are :
Stage 0 - This stage have high lymphocytes (a type of WBC) count in the blood, but there are no other symptoms of leukemia. It is a slow-growing stage and patients are at low risk.
Stage 1 - Lymph nodes are larger than normal because of high lymphocytes count. Patients are at intermediate risk
Stage 2 - Lymph nodes, liver and spleen are larger than normal as a result of an overabundance of lymphocytes. Patients are at intermediate risk
Stage 3 - Anemia has developed because there are too few red blood cells in the blood. Lymph nodes, spleen and liver may be swollen because of high lymphocytes count. Patients are at high risk
Stage 4 - There are too few platelets in the blood. Lymph nodes, spleen and liver may be swollen. Anemia may be present.
Binet staging system classifies CLL according to which lymphoid tissues, such as the spleen or lymph nodes, are involved as well as the presence of low red blood cell count (anemia) or low number of blood platelets (thrombocytopenia). The major advantage of the Binet system is its ability to highlight the splenic form of CLL.
The stage of binet system are :
Stage A - There are three or fewer areas of enlarged lymph tissue. Lymph nodes in one particular area, such as the neck or underarm, are considered one group, whether they occur on just one side of the body (unilateral) or on both sides (bilateral).
Stage B - There are more than three areas of enlarged lymph tissue.
Stage C - Enlarged lymph tissue is present along with anemia and thrombocytopenia.
Methods of treatment
The doctor is the best person to describe the treatment choices and discuss the expected results.Depending on the type and extent of the disease, patients may have chemotherapy, biological therapy, radiation therapy, or bone marrow transplantation. If the patient's spleen is enlarged, the doctor may suggest surgery to remove it. Some patients receive a combination of treatments.People with acute leukemia need to be treated right away. The goal of treatment is to bring about a remission. Then, when signs and symptoms disappear, more therapy may be given to prevent a relapse. This type of therapy is called maintenance therapy. Many people with acute leukemia can be cured.
Chronic leukemia patients who do not have symptoms may not require immediate treatment. The doctor may suggest watchful waiting for some patients with chronic lymphocytic leukemia. The health care team will monitor the patient's health so that treatment can begin if symptoms occur or worsen. When treatment for chronic leukemia is needed, it can often control the disease and its symptoms. However, chronic leukemia can seldom be cured. Patients may receive maintenance therapy to help keep the cancer in remission. A patient may want to talk to the doctor about taking part in a clinical trial, a research study of new treatment methods. The section on "The Promise of Cancer Research" has more information about clinical trials. In addition to anticancer therapy, people with leukemia may have treatment to control pain and other symptoms of the cancer, to relieve the side effects of therapy, or to ease emotional problems. This kind of treatment is called symptom management, supportive care, or palliative care.
Most patients with leukemia are treated with chemotherapy. It is the treatment using anti-cancer drugs to destroy cancer cells. Depending on the type of leukemia, patients may receive a single drug or a combination of two or more drugs. Most of the drugs are given by IV injection (injected into a vein) through a thin, flexible tube called catheter. One end of the tube is placed in a large vein, often in the upper chest and the drugs are injected through this. These drugs entering into the bloodstream, affect leukemia cells in most parts of the body but do not reach cells in the central nervous system because they are stopped by the blood-brain barrier. To reach leukemia cells in the central nervous system, intrathecal chemotherapy is given. This is the method of injecting drugs directly into the cerebrospinal fluid through a special type of catheter called Ommaya reservoir. The catheter is placed under the scalp and the doctor injects the anticancer drugs into it. This method avoids the discomfort of injections into the spine. Chemotherapy is given in cycles : a treatment period followed by a recovery period and then another treatment period, and so on. Depending on which drugs are given, and the patient's general health, a hospital stay may be necessary.Some people with chronic myeloid leukemia receive a new type of treatment called targeted therapy. This treatment use drugs or other substances to identify and attack specific cancer cells without harming normal cells. It also blocks the production of leukemia cells. A monoclonal antibody is a type of targeted therapy
Side Effects : Side effects of chemotherapy depends mainly on the drugs and doses received, as well as how the drugs are given and it vary from patient to patient. When chemotherapy affects healthy cells, it can lower patients' resistance to infection, and patients may have less energy and bruise or bleed easily. Common side effects of chemotherapy include nausea, vomiting, hair loss, diarrhea, poor appetite and mouth sores. Most side effects disappear gradually during the recover periods between treatments or after treatment stops. Some drugs can affect the patient's fertility. Because targeted therapy affects only leukemia cells, it causes fewer side effects than most other anticancer drugs.
Radiation therapy
Radiation therapy alias radiotherapy uses high-energy rays to damage cancer cells and stop them from growing. The radiation comes from a large machine. Radiation therapy for leukemia can be given in two ways. For some patients, the doctor may direct the radiation to one specific area of the body where there is a collection of leukemia cells, such as the spleen, brain or testicles. Some may receive radiation that is directed to the whole body. This type of radiation therapy, called total-body irradiation, usually is given before a bone marrow transplant.
Side Effects : Radiation can cause the scalp or the skin in the treated area to become red, dry, tender, and itchy. It can cause tiredness, hair loss, nausea, vomiting, and loss of appetite. Other side effects depend on the area of the body that is treated. Most side effects will be disappear after treatment but some may be last. Children (especially young ones) who receive radiation to the brain may develop problems with learning and coordination.
Stem Cell Transplantation
It is the method of replacing immature blood-forming cells that were destroyed by cancer treatment. A stem cell transplant allows a patient to be treated with high doses of drugs, radiation, or both. The high doses destroy both leukemia cells and normal blood cells in the bone marrow. Later, the patient receives healthy stem cells through a flexible tube that is placed in a large vein in the neck or chest area. New blood cells develop from the transplanted stem cells.
Bone marrow transplantation, peripheral stem cell transplantation and umbilical cord blood transplantation are the three types of transplantation. Bone marrow transplantation is the procedure of replacing bone marrow and peripheral stem cell transplantation is the method of replacing blood-forming cells. In umbilical cord blood transplantation, umbilical cord blood from a newborn baby which contain high concentrations of stem cells needed to produce new blood cells, is injected to restore an individual's own blood production system suppressed by anticancer drugs, radiation therapy or both. Transplantation may be autologous, allogeneic or syngeneic.
Autologous stem cell transplantation - Patients own stem cells are used in this transplantation. The stem cells are removed and treated outside the body to kill any leukemia cells. It is then frozen and stored. These stored cells are returned to the patient, after receiving high dose chemotherapy or radiotherapy.
Allogeneic stem cell transplantation - In this transplantation the healthy stem cells come from a donor. Blood test is done to make sure that the donor's cells match the patient's cells.
Syngeneic stem cell transplantation - This type of transplant uses stem cells from the patient's healthy identical twin.
Patients who have a stem cell transplant usually stay in the hospital for several weeks. Until the transplanted stem cells begins to produce enough white blood cells, patients have to be carefully protected from infection.
Side Effects: SPatients who have a stem cell transplantation face an increased risk of infection, bleeding, and other side effects of the large doses of chemotherapy and radiation they receive. In addition, graft- versus-host disease (GVHD) may occur in patients who receive bone marrow from a donor. In GVHD, the donated marrow reacts against the patient's tissues (most often the liver, the skin, and the digestive tract). GVHD can be mild or very severe. It can occur any time after the transplant (even years later). Drugs may be given to reduce the risk of GVHD and to treat the problem if it occurs
Biological Therapy
Biological therapy involves treatment with substances that affect the immune system's response to cancer. This type of treatment improves the body's natural defenses against cancer. The therapy is given by injection into a vein. Biological therapies like interferon and monoclonal antibody are used in chronic myeloid leukemia and chronic lymphocytic leukemia respectively. These naturally occurring compounds are directly inserted through a catheter to slow the growth of leukemia cells.
Side Effects : The side effects of biological therapy differ with the types of substances used and from patient to patient. Rashes or swelling where the biological therapy is injected are common. Flu-like symptoms also may occur. The goal of treatment is to bring about a remission. Remission means a decrease in or disappearance of signs and symptoms of cancer. In partial remission, some signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although cancer may still be in the body.
Other Therapy
The following therapies have proponents but no scientific evidence of unequivocal benefit:
Coenzyme Q10
Polysaccharide K
Alternative or complementary therapies should be discussed with the treating specialist. These therapies are not offered in conjunction with chemotherapy for leukemia because of the lack of definitive data.
What happens after treatment for leukemia
Supportive care
Leukemia and its treatment can lead to other health problems. Patients receive supportive care to prevent or control these problems and to improve their comfort and quality of life during treatment. Because people with leukemia get infections very easily, they may receive antibiotics and other drugs to help protect them from infections. The health care team may advise them to stay away from crowds and from people with colds and other contagious diseases. If an infection develops, it can be serious and should be treated promptly. Patients may need to stay in the hospital for treatment.
Anemia and bleeding are other problems that often require supportive care. Patients may need transfusions of red blood cells to help them have more energy. Platelet transfusions can help reduce the risk of serious bleeding. Dental care also is very important. Leukemia and chemotherapy can make the mouth sensitive, easily infected, and likely to bleed. Doctors often advise patients to have a complete dental exam and, if possible, undergo needed dental care before chemotherapy begins. Dentists show patients how to keep their mouth clean and healthy during treatment.
Followup care
Followup care after treatment for leukemia is an important part of the overall treatment plan. Regular checkups ensure that any changes in health are noted. The doctor can find problems and treat them as soon as possible. Checkups may include a careful physical exam, blood tests, x-rays, bone marrow aspiration, or spinal tap. The doctor can explain the followup plan”how often the patient must visit the doctor and what tests are needed. The NCI has prepared a booklet for people who have completed their treatment to help answer questions about followup care and other concerns.
Cancer Prevention
A number of risk factors contribute to the formation of cancer. Although there are many risk factors for cancer you cannot control, there are changes you can make to your lifestyle to decrease your risk of cancer. Factors such as genetics cannot be controlled; others, like cigarette smoking, can be. Both your lifestyle and environment may affect your chances of developing certain types of cancer.
All cancers are different, so they have different causes. A factor that may contribute to lung cancer may not contribute to cervical cancer. Knowing the risk factors for different cancer types can give you the power to prevent certain cancers from ever forming.
It can be difficult to determine the cause of cancer. Multiple risk factors work together to contribute to its development. The following are some actions that can help prevent different types of cancer:
Quit smoking to reduce the chances of getting lung cancer
Reduce alcohol intake to avoid esophageal cancer
Eat well-balanced and nutritious meals to inhibit the formation of colon cancer
Exercise and stay active to reduce the likelihood of developing colon or breast cancer. Get vaccinated against hepatitis B, a virus that can cause liver cancer .
Avoid prolonged exposure to the sun and use sunscreen to prevent melanomas and skin cancer
Be aware of your environment. Avoid hazardous jobs that expose you to radiation or other carcinogenic substances
While there may be no sure way of preventing a person from getting cancer, following these guidelines as well as a healthy lifestyle is a great way to help reduce your risk.
Well-balanced diet and good nutritional habits are key to a life. Poor nutrition and a lack of physical activity leading to obesity account for approximately one-third of all cancer deaths. As a result, managing weight and eating well is important to reducing the risk of developing cancer.
Some things to consider
Eat well to establish a healthy weight and avoid becoming overweight or obese
Eat smaller portions to reduce the number of calories
Eliminate high-calorie foods, such as sweets and fatty foods
Replace unhealthy food with more servings of fruits and vegetables
Exercise to burn calories
Moderate physical activity a few days a week will help to keep a healthy weight
Drink less alcohol
Limit drinking to 1 or 2 drinks per day, at most
Some steps one can take toward a better diet are:
Eat at restaurants less often for more control over what and how you eat
Cheat a little bit to satisfy cravings
Plan ahead”create personalized menus and shop with purpose
Choose natural food and ingredients rather those heavily processed
Melting Point = 220 oC
Average Molecular Weight = 268.2691
Toxicity LD50=128 mg/kg (mouse), side effects include lethargy, rash, fatigue, nausea and
Chemical IUPAC Name: 8-[4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-4,6,8,10-tetrazabicyclo[5.3.0]deca-4,9,11-trien-2-ol
Pentostatin is also known by the following brand names and/or synonyms2'-DCF; 2'-Deoxycoformycin; 2'-Dexoycoformycin; 2â„¢-Dexoycoformycin; CI-825; CL67310465; Co-V; Co-Vidarabine; Covidarabine; Dcf; Deaminase Inhibitor; Deoxycoformycin; Nipent; PD-ADI; Pentostatin; Vidarbine; Vira a Deaminase Inhibitor
Drug Category:
Pentostatin is categorized under the following by the FDA: Immunosuppressive Agents; Antibiotics; Antineoplastic Agents; ATC:L01XX08
Absorption: - Not absorbed orally, crosses blood brain barrier
Interactions for Pentostatin:
Interactions with cylcopholsphamide, fludarabine and vidarabine.
Ligand Detailed Information
Detailed Information
Name Pentostatin
Synonym Pentostatin, ®-2'-Deoxycoformycin, ®-3-(2-Deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo(4,5-d)(1,3)diazepin-8-ol, ®-Deoxycoformycin
BRN 1223097, CI-825, CL 67310465, CO-Vidarabine
Deaminase inhibitor (PD)
inhibitor for adenosine arabinoside
3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydro-, ®-
CAS 53910-25-1
Formula C11H16N4O4
Class Antibiotics
Drug / Therapeutic Agent
Enzyme inhibitors
Immunosuppressive agents
Pentostatin (2-deoxy-coformycin or DCF) is a purine nucleoside analogue (PNA).
Pentostatin is a cancer (antineoplastic) medication. Pentostatin interferes with the growth of cancer cells and slows their growth and spread in the body.
Pentostatin is used to treat a specific type of blood cancer (hairy cell leukemia).
It is a cytotoxic agent with high activity in a variety of lymphoid and myeloid malignancies, exerting cytotoxic effect in both proliferating and quiescent cells.
It has a well established place in treatment of hairy cell leukaemia.
In recent years lower dose combination regimens with pentostatin have been developed which may have profound effects on complete remission rates and, ultimately, cure in some chronic lymphocytic leukaemias (CLL).
Low dose combination regimens with pentostatin appear to be active and very promising in other lymphoproliferative diseases.
Mechanism Of Action:
Pentostatin is a potent transition state inhibitor of adenosine deaminase (ADA), the greatest activity of which is found in cells of the lymphoid system. T-cells have higher ADA activity than B-cells, and T-cell malignancies have higher activity than B-cell malignancies. The cytotoxicity that results from prevention of catabolism of adenosine or deoxyadenosine is thought to be due to elevated intracellular levels of dATP, which can block DNA synthesis through inhibition of ribonucleotide reductase. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase).
Mode of action
The PNAs share similar chemical structure and mode of action.
The cytotoxic effect is exerted through a variety of mechanisms (inhibition of DNA synthesis and repair, mitochondrial pathways etc) culminating in apoptosis.
It is a strong inhibitor of adenosine deaminase, an important degradative enzyme in purine metabolism which is present in all human tissues but in higher concentration in lymphoid tissue.
Synergistic actions have been demonstrated between PNAs and other cytotoxic agents (such as the alkylating agents, anthracycline antitumour antibiotics, cytacarbine and monoclonal antibodies) which explain the enhanced benefits of combination regimens.
Pentostatin and fludarabine is the treatment of choice in hairy cell leukaemia, but other combinations with pentostatin have been used. A report from the Marsden of 219 patients treated with PNAs showed that with pentostatin 96% of patents showed a complete response with relapse rates of 24% at 5 years and 42% at 10 years. Survival at 10 years was 96%.
Pentostatin is highly effective in:
o Chronic lymphatic leukaemia (CLL)
o Low grade B and T cell non Hodgkin's lymphomas, including Waldenstrom's macroglobulinemia
o T-cell cutaneous lymphomas
Controlled trials have shown pentostatin to be effective in:
o Acute myeloid leukaemia
o Myelodysplastic syndromes
Pentostatin has an important role in non-myeloablative regimens in allogenic stem cell transplantation
Administration and treatment regimens
When introduced pentostatin was given in high doses for acute lymphoblastic leukaemias. New regimens have been developed and are being developed for a wider range of disease. In general it is being given in lower dosages and in combination regimens:
It is given intravenously. 10mg vials of powder for reconstitution costs over £800
It is usually given every 2-3 weeks in cycles (e.g. 6 cycles).
Dosages are low (e.g. 4mg/ sq metre in previously treated CLL).
It is given most appropriately in specialist centres.
Patients are likely to be involved in trials which are needed to further improve regimens and define relative benefits. For example in CLL, in relapsed CLL and non-Hodgkin's lymphoma for indolent lymphoproliferative disorders,peripheral T-cell lymphomas.
It is likely to be used in combination regimens to take advantage of the synergism with other agents (e.g. alkylating agents and monoclonal antibodies).
Adverse effects
The low dose regimens appear to be well tolerated.It is even well tolerated in elderly patients.
It is less myelosuppressive than other PNAs and not toxic to myeloid progenitors (hence use in autologous stem cell transplant patients).
The main problems arise from the prolonged immunosuppression. Opportunistic infections are a problem and there should be awareness of this amongst all involved in the care of treated patients. This has implications for shared care protocols and communication between specialist centres, patients and the primary health care team.
This medication is used to treat:
hairy cell leukemia
chronic lymphocytic leukemia
This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.Pentostatin is a type of antibiotic that is only used for chemotherapy; it slows or stops the growth of cancer cells in your body. The length of treatment depends on the types of drugs you are taking, how well your body responds to them, and the type of cancer you have.
Other uses for this medicine
Pentostatin also is used to treat acute lymphocytic leukemia, mycosis fungoides, prolymphocytic leukemia (B-cell and T-cell origin), T-cell leukemia, and lymphoma. Talk to your doctor about the possible risks of using this drug for your condition.
Side effects
Side effects from Pentostatin are common and include:
nausea and vomiting
loss of appetite
upset stomach
abdominal pain
gum and teeth changes
Tell your doctor if either of these symptoms is severe or lasts for several hours:
tiredness or fatigue
mouth blistering
If you experience any of the following symptoms or those listed in the IMPORTANT WARNING section call your doctor immediately:
unusual bleeding or bruising
sore throat
muscle aches
pain (especially chest pain or discomfort)
redness, swelling, or pain at the site of injection
anxiety or depression
eye or ear pain
1. Introduction :
Adenosine Deaminase: . A hydrolytic enzyme that catalyzes the reaction between adenosine and water producing inosine and ammonia. Amino group is removed from adenosine (A) to produce inosine (I). The reaction is a part of the purine salvage mechanism. Pentostatin (Nipent), a potent inhibitor of adenosine deaminase, has activity in a wide range of lymphoid malignancies A deficiency of this enzyme produced by genetic abnormality has been found in many individuals with severe combined immunodeficiency syndrome.
Scientists are also trying to destabilize pathogens like HIV by creating single point mutations in their RNA genome where an A is mutated to become an I. Because an I looks very much like G (guanosine), as shown below, it forms IC base pairs which will lead to GC base pairs where C is cytosine in the next generation. ADA is a cytosolic enzyme, which has been the object of considerable interest, mainly because in human a congenital defect in the enzyme causes severe combined immunodeficiency disease (SCID). ADA participates in the purine metabolism where it degrades either adenosine or 2â„¢-deoxyadenosine producing inosine or 2â„¢- deoxyinosine, respectively. Further metabolisation of these deaminated nucleosides leads to hypoxanthine, which can be either transformed into uric acid by xanthine oxidase or salvaged into mononucleotides by the action of hypoxanthine-guanine phosphoribosyl-transferase. Different laboratories have shown that ADA may appear also on the cell surface (ecto-ADA, see review by (Franco et al., 1997)). Only one human gene for ADA has been detected which codes for a protein lacking both signal peptide and putative transmembrane domains. There probably exists some specific mechanism of ADA release. It should be noted that there are important growth factors (e.g. interleukin-1b) lacking signal peptides whose mechanism of secretion is also not known. No differences in catalytic activity between cytosolic ADA and ecto-ADA have been found. In addition, ecto-ADA could have functions independent of its enzymatic activity. Ecto-ADA could bind directly to at least three different cell surface molecules, human CD26 (a lymphocytes activation marker), and A1 and A2B adenosine receptors. In such a context, ADA probably acts as a co stimulatory molecule of adenosine receptors and/or CD26 (Martin et al., 1995; Ciruela et al., 1996; Herrera et al., 2001)
Target Information
Name Adenosine deaminase
Type of target Successful target
Targeted by Dipyridamole
EC Number EC
Synonyms Adenosine aminohydrolase
Disease Acute myeloid leukemia
Chronic lymphocytic leukemia
Chronic myeloid leukemia
Hairy-cell leukemia
Non-Hodgkin's lymphoma, unspecified type
Peripheral and cutaneous T-cell lymphomas
Inhibitor 2'-deoxycoformycin
Cladribine Fludarabine Pentostatin 2. Structure of Adenosine Deaminase
The product of human ADA gene consists of 363 amino acids (41 kDa) and there is a high degree of amino acids sequence conservation amongst species. The enzyme contains a parallel a/b-barrel motif with eight central b strands and eight peripheral a helices, which is common structure found in 1/10 of known enzymes (Farber and Petsko, 1990)); it also contains five additional helices. The oblong-shaped deep active site is lined by the COOH-terminal segments and connecting loops of the b-barrel strands. The active site also contains a zinc atom, which participates directly in the deamination mechanism. There are several hydrogen bonds between the substrate and the enzyme that stabilize the binding of substrate and the transition state.
Chang et al. (1991) proposed that catalytic functions are carried out by Cys 262, Asp 295, Asp 296, and His 214 of the mammalian adenosine deaminases. The zinc ion is coordinated by His 15, His 17, His 214 and Asp 295. From following studies (Wilson and Quiocho, 1993; Mohamedali et al., 1996; Sideraki et al., 1996), the mechanism for deamination was proposed, in which the zinc cofactor activates a liganded water molecule from which the nearby His 238 abstracts a proton, thus creating the attacking hydroxyl group. The incipient hydroxyl is orientated for attack on the C6 of the substrate through its interaction with Asp 295, His 238, and the zinc. Asp 295 is thought to hydrogen bond to the catalytic water and share a zinc ligand site with it. The protonated Glu 217 facilitates the reaction by donating a hydrogen bond to N1 of the purine, thus enabling the formation of tetrahedral C6. His 238 is possible candidate as a source of the proton added to the amino leaving group. Residues Asp 296 and Gly 184 participate in hydrogen bonds with N7 and N9 of adenosine.
In vitro mutagenesis of three residues coordinating the zinc atom (His 17, His 214, Asp 295) eliminated ADA activity (Bhaumik et al., 1993). Many of the point mutations thus far examined affect residues lodged in the b strands. Since the active site pocket, with a bound zinc, is lined by parts of the b strands, it is likely that any mutation that causes a misalignment of the b strands would have a deleterious effect on activity (Wilson etal., 1991).
4. Physiological roles of ADA and adenosine :
Additionally to the key role in the purine metabolism, i.e. degradation and/or conversion of adenosine/deoxyadenosine, ADA has also important physiological roles. These roles according to the present knowledge can be divided to
1. enzymatic activities both of cytosolic and ecto-ADA via the regulation of a concentration of both intracellular and extracellular adenosine
2. extraenzymatic activities of ecto-ADA via the binding to the cell surface molecules .
4.1. Enzymatic activity of ADA “ adenosine actions
First, physiological roles of ADA can be seen in connection with adenosine whose concentration can be modulated by enzymatic action of ADA. Adenosine is both a metabolic precursor for nucleic acids (intracellular adenosine) and a significant signalling molecule involved in regulation of various physiological processes. The physiological functions of adenosine are thought to be linked to its localized release (extracellular adenosine - Ado). Ado triggers the changes within the cells through its interaction with adenosine receptors. The responses to adenosine include coronary vasodilatation, reduction in heart rate and contractile force, inhibition of platelet aggregation, mast-cell degranulation, inactivation of eosinophil migration, renal vasoconstriction, regulation of ion channel activity, membrane potential and neurotransmitter and hormone release (Nyce, 1999). In some tissues the release of adenosine has been shown to be stimulated by hypoxia (Ado may also play a role in angiogenesis (Adair et al., 1990). Beside these effects, recent reports describe Ado as a novel modulator of cell proliferation and differentiation These effects of Ado are again triggered through adenosine receptors.
4.1.1. Adenosine receptors
Adenosine receptors, as other G protein-linked receptors, contain seven transmembrane domains, with an intracellular carboxy terminus and an extracellular amino terminus.
There were identified 4 types of adenosine receptors in mammals. A1 and A3 receptors interact with G proteins Gi and A2a and A2b with Gs. They are typically coupled to the adenylate cyclase-cAMP signal-transduction pathway. A1 and A3 also signal via phospolipase C (PLC) and Ca2+.The most widely recognized signaling pathway of A1 receptors is inhibition of adenylate cyclase causing a decrease in the second-messenger cAMP (Munshi et al., 1991) that in turn modulates the activity of cAMP-dependent protein kinase. Another signaling mechanism of A1 receptors is activation of PLC leading to membrane phosphoinositide metabolism and increased production of IP3 (and DAG) and Ca2+ mobilization (Iredale et al., 1994). Elevation of cytosolic Ca2+ by IP3 can stimulate a variety of signaling pathways, including a family of protein kinase C (PKC), phospolipase A2 (PLA2), Ca2+-dependent K+ channels, and nitric oxide synthase (NOS).
Schematic picture of transmembrane arrangement of adenosine receptor
The A3 receptor has also been shown to inhibit adenylate cyclase activity (Zhou et al., 1992). It is coupling to Gia2-, Gia3- and, to a lesser extent, to Gq/11 proteins and stimulates PLC and elevates IP3 levels and intracellular Ca2+.
The most commonly recognized signal transduction mechanism for A2A and A2B receptors is, on the other hand, activation of adenylate cyclase. This implies coupling with the G protein Gs
Expression of more than one type of adenosine receptor on the same cell may allow the common agonist of adenosine to activate multiple signaling pathways. Adenylate cyclase is a common effector, which is negatively coupled to A1 and A3 receptors and positively coupled to A2 receptors, affording the opportunity for reciprocal control and, therefore, fine tuning of this signaling pathway. The extracellular adenosine concentration may be a crucial determinant of the differential activation of coexisting adenosine receptors under pathophysiological as well as physiological conditions. Overexpression of the A2 adenosine receptor in mice promoted gland hyperplasia. Catherine Ledent and colleagues generated transgenic mice expressing the canine A2 adenosine receptor under control of the bovine thyroglobulin gene promoter (Ledent et al., 1992). This promoter targets the expression of a reporter gene to the thyroid cells with a very tight specificity. High level of A2 receptor transcript and the presence of a functional receptor were detected in transgenic thyroids. This correlated with increased levels of cAMP in the thyroid of transgenic animals, demonstrating that the A2 adenosine receptor acts in vivo as a constitutive activator of adenylyl cyclase. Expression of the A2 adenosine receptor promoted gland hyperplasia and severe hyperthyroidism. The progressive heterogeneity of the tissue in older mice and the presence of dense tissue nodules suggested that the stimulation of adenylyl cyclase could eventually favor the development of thyroid cancer.
Extracellular adenosine inhibits DNA synthesis induced by TSH in FRTL-5 thyroid cells through the A1 adenosine receptor-Gi system (Sho et al., 1999). TSH promotes G1 cyclin expression by inducing cAMP production. This cyclin expression then triggers cell cycle progression from the G0/G1 to the S phase. PIA inhibited the TSH induction but not inhibited dibutyryl cAMP, a cell-permeable cAMP derivative, induction of cell cycle progression. The inhibitory actions of PIA on the TSH actions were prevented by the treatment of the cells by pertussis toxin, which is an inactivator of Gi. Therefore, PIA actions are performed by the activation of the A1 adenosine receptor and inactivation of adenylyl cyclase by Gi coupled with the A1 receptor. Previously, these authors also showed that in FRTL-5 cells both adenosine and PIA inhibited the TSH-induced cAMP production; whereas, in the absence of TSH, the agonist stimulated cAMP production in the cells where the A1 receptor-mediated pathway was inactivated by the pertussis toxin (Nazarea et al., 1991). This suggests that, in FRTL-5 cells, both A1 and A2 adenosine receptors coexist; the A1 receptor mediates an inhibitory signal for adenylyl cyclase through Gi, and the A2 receptor is responsible for activating adenylyl cyclase through Gs. Additionally to expression of different adenosine receptor on the cell surface, any of previously described actions of adenosine can be potentially influenced by two mechanisms regulating the concentration of adenosine:
Transportation of adenosine across the cell membrane
Enzymatic regulation of adenosine concentration by ADA.
4.1.2. Adenosine transportation
The termination of adenosine actions with its receptor involves its transport across the plasma membrane and subsequent metabolism. Adenosine is hydrophilic and specialized transport systems are required for its movement across the cell membrane. There exist two types of nucleoside transport systems in mammalian cells “ facilitated-diffusion nucleoside transport (equilibrative adenosine carriers) and active transport driven by an inwardly directed transmembrane sodium gradient (Na+/adenosine cotransporters). Inhibition of these transporters potentiates the actions of adenosine. Because of the relatively high activity of intracellular adenosine kinase, adenosine concentrations inside cells are normally low, so the net flux through the equilibrative transporters is inwardly directed. However, under conditions where intracellular adenosine concentrations rise, these transporters can release adenosine.In the heart, hypoxia produces a profound inhibition of adenosine kinase activity (to as low as 6% of normal activity) Inhibition of adenosine kinase probably has little effect on ATP levels, but it generates large amounts of adenosine & profoundly increases adenosine release.
4.1.3. Regulation of adenosine concentration by ADA and consequences
It is clear that ADA may potentially influence any previously described actions of adenosine through its enzymatic regulation of adenosine concentration. For example, Lelievre et al., (1998a; 1998b) showed that ADA can modulate cell growth in colon cancer cell lines. Additionally, Dexter et al., 1981 showed that agents that trigger colon cancer cell line HT29 differentiation also trigger modifications in the activity of ADA. Thus, adenosine deaminase-induced extracellular adenosine deprivation may result in the selection of differentiated cells. Lelievre et al. (2000) demonstrated that a concomitant down-regulation of adenosine A1 receptors and up regulation of adenosine A2 receptors occurred in cloned cells of colon cancer cell line with a strong reduction in proliferation. Colquhoun and Newsholme, 1997 showed that removal of exogenous adenosine by growth in the presence of adenosine deaminase also inhibited the proliferation of other human tumor cells. However, in contrast to previous paragraphs adenosine can stimulate the proliferation of other cells types. For example, Ethier et al. (1993) found that addition of physiological concentration of Ado to human umbilical vein endothelial cell cultures stimulated proliferation. Or, the release of adenosine under certain conditions in the brain can stimulate in presence of both adenosine A1 and A2 receptors the proliferation of microglial cells (Gebicke-Haerter et al., 1996). MacLaughlin et al., 1997 demonstrated that Ado induced mesengial cell proliferation by a mechanism that seems to involve both adenosine A1 and A2 receptor type activation and increase in both second messengers, cytosolic free calcium and cAMP.
Adenosine deaminase has also been shown to impair the insulin sensitivity for glucose transport and antilipolysis by inactivating extracellular adenosine, which adipocytes release spontaneously (Green, 1987). Takasuga and coworkers showed that adenosine enhanced both the insulin-induced accumulation of PIP3 and the insulin-induced activation of PKB by a mechanism independent of its inhibitory action on adenylyl cyclase (Takasuga et al., 1999):
Insulin induces in rat adipocytes the production of PIP3 by PI 3-kinase. Treatment of cells with adenosine deaminase suppresses the insulin-induced production of PIP3. Rat adipocytes spontaneously release adenosine, which in turn binds to the A1 receptors on the cells. Degradation of this adenosine by addition of adenosine deaminase modulates the insulin action on glucose uptake. Inhibitors of the adenosine A1 receptors also inhibit the insulin-induced PIP3 production, which supports that adenosine deaminase modulates the insulin action by eliminating the adenosine action on the A1 receptors.

When the spontaneously released adenosine was inactivated by adenosine deaminase, PIA, a poorly hydrolysable analogue of adenosine, effectively enhanced the insulin-induced PIP3 production. PGE2, which activates the GTP-binding proteins in the cells, also increases the accumulation of the insulin-induced PIP3, even if inhibitors of the adenosine A1 receptors are present.
Insulin is known to activate rapidly a serine/threonine kinase PKB in rat adipocytes (Wijkander et al., 1997). The activity of PKB is increased by lipid products of PI 3-kinase (Franke et al., 1997). Incubation of the cells with adenosine deaminase attenuates the insulin-induced activation of PKB. Addition of PIA reverses the PKB activity to the level of insulin alone and PGE2 also increased the PKB activity in the presence of both insulin and adenosine deaminase.
4. Direct inhibition of adenylyl cyclase by DDA did not affect the insulin actions on PIP3 and PKB.
Pak et al. (1994) showed that adenosine deaminase inhibitors have little or no influence on the concentration of extracellular adenosine in nervous system. However, adenosine usually comprises <10% of the total purine efflux in hippocampus, whereas the remainder appears as the adenosine metabolites inosine, hypoxanthine, or xanthine (Lloyd et al., 1993), which imply that adenosine deaminase is relatively important in clearing the extracellular adenosine. The resolution of these seemingly paradoxical observations according to Dunwiddie and Masino (2001) is that the majority of adenosine in the extracellular space is cleared via reuptake; however, any metabolites that are formed are much more likely than adenosine to diffuse out of the slice without being recaptured and, hence, make a disproportionate contribution to purine efflux.
4.2. Extraenzymatic activities of Ecto-ADA
Ecto-ADA could have functions independent of its enzymatic activity. These extraenzymatic functions have been linked to the binding of ecto-ADA directly to at least three different cell surface molecules: CD26 (a lymphocytes activation marker), A1 and A2B adenosine receptors. In such a context, ADA probably acts as a co stimulatory molecule of adenosine receptors and/or CD26 (Martin et al., 1995; Ciruela et al., 1996; Herrera et al., 2001).
4.2.1. Ecto-ADA interaction with CD26
The first cell surface protein able to bind ADA was identified in 1993 as human CD26 by (Kameoka et al., 1993). The CD26 protein has been extensively studied in T-lymphocytes (for review see De Meester et al., 1999), where its physiological role seems to be related to T-cell activation (when cells become activated, the level of CD26 expression increases markedly). But CD26 is found in many cell types, even in resting T cells (Franco et al., 1997). CD26 has an enzyme activity, which consists of the cleavage of dipeptides from N-terminus of polypeptides having Pro at the penultimate position (therefore CD26 is also called dipeptidyl peptidase IV “ DPPIV). But neither the physiological substrate nor the exact physiological role of the enzymatic activity is known.
Dong et al. (1996) demonstrated that neither the protease activity nor the deaminase activity are required for the association between CD26 and ecto-ADA. They also showed that ADA on the cell surface could be derived from the intracellular ADA of cells. They found that the human CD26-transfected murine pre-B cell line did not co-express ADA on the cell surface, as shown by anti-ADA Ab (human ADA specific; murine ADA doesnâ„¢t bind to the human CD26), although human CD26 was clearly expressed on the cell surface. The overnight co culture of human CD26 transfectants with CD26-negative parental Jurkat cells resulted in a high expression of human ADA on the cell surface of human CD26 transfectants by two-color immunofluorescence analysis. This result showed that ADA inside the cells could be released into the medium, either actively or passively, and could bind to CD26 on the cell surface of other cells. Martin et al. (1995) demonstrated that ecto-ADA could act as a co-stimulatory molecule. Cell proliferation is accelerated when peripheral T cells are activated in the presence of exogenous ADA. In contrast, T cells became anergic in the presence of anti-ADA antibodies, which do not modify the enzymatic activity. Thus, a molecular interaction between ADA and CD26 was needed for the activation of peripheral blood T cells. Despite the high similarity between murine and human ADA, neither does murine ADA interact with human or murine CD26 nor does murine CD26 interact with human or murine ADA (Franco et al., 1998). Thus it seems that interaction between ADA and CD26 is probably restricted to human.
4.2.2. Ecto-ADA binding to adenosine receptors
Rafael Francoâ„¢s group found that ADA interacts with at least two types of adenosine receptors. First, they found that in pig brain cortex membranes ADA interacts with A1R adenosine receptor (Saura et al., 1996). Recently, they demonstrated that in transfected Chinese hamster ovary cells and Jurkat J32 T lymphocytes ADA anchors to adenosine receptors of the A2B subtype (Herrera et al., 2001). These data constitute the first evidence demonstrating an interaction between a degradative ecto-enzyme (i.e. ecto-ADA) and the receptor whose ligand (i.e. adenosine) is the enzyme substrate.
Franco et al. (1998) suggest that the interaction ecto-ADA/A1R is necessary for high-affinity binding of Ado and subsequently for allowing efficient signal transduction (high-affinity binding component of the A1 receptor was identified only in the presence of exogenous ADA). They also found that low concentration of Hg2+ completely abolished ADA activity without affecting the ADA-induced enhancement of second messengers via A1R. Thus it seems that enzymatic activity of ADA is not required for this type of ADA action and it can probably acts as a co stimulatory molecule.
Molecule - adenosine deaminase
Type : polypeptide
Length: 415
Structure Weight: 43893.46
PDB ID- 2pgr

Resolution [Ao] - 2.30
R value - 0.171 (obs.)
R free - 0.220
Space Group - 0.220
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