Breaking News…..

GoogleNews.com, FORBES.COM, July 12, 2010, by Julie Pace  —  WASHINGTON — President Barack Obama will unveil a new national strategy for combating HIV and AIDS Tuesday (today) that aims to reduce new infections in the U.S. by 25 percent over the next five years.

A source who advised the administration on the strategy says it also calls for increasing access to care for people living with HIV. Among the goals is making sure that 85 percent of patients begin receiving care within three months of diagnosis.

The new policy will concentrate HIV prevention efforts at the highest-risk populations, which include gay and bisexual men, as well as black Americans.

The source spoke on the condition of anonymity to discuss the report ahead of the president’s announcement.

Sinus Surgery:

Sinuses are air-filled cavities in the skull that allow mucus to drain into the nasal passages. But they can get infected. And reinfected. In Seth Hamblin¿s case, years of chronic sinus infections led him down the path to image-guided endoscopic sinus surgery and, eventually, to better breathing.

SOURCE: Washington ENT Group | GRAPHIC: Brenna Maloney And Laura Stanton – The Washington Post

What is Sinusitis?

Tiny hair-like structures called cilia (magnified here) help move mucus across sinus membranes and toward an exit. All of your sinus cavities connect to your nose to allow a free exchange of air and mucus.Infections or allergies make sinus tissues inflamed, red, and swollen. That’s called sinusitis.

July 12, 2010, by Gabe Mirkin MD – Every doctor eventually realizes how difficult it is to treat sinusitis. Most of you who have been diagnosed as having sinusitis, and have sought help from allergists, ear-nose-and-throat-doctors, internists or surgeons, know that you still have sinusitis, even though you may have had surgery, allergy shots, all kinds of medications and shots or any other treatment.

Many people find relief with saline irrigation, using various devices that are readily available in drugstores; check with your doctor or pharmacist for their recommendations.

Your sinuses are cavities containing air in the bones of your head. They make your head lighter. If the bones in your head were solid, your head would weigh more than 50 pounds, your neck would not be able to hold it up or turn it, and the human race would never have survived in competition with other animals. The problem with having sinuses is that the air in a sinus cavity must always have the same air pressure as the air outside, so all sinuses must have passageways to the outside that allow the pressure inside a sinus to be equal to the outside pressure.

If the barometric pressure drops suddenly, as it does often before a storm, and your sinus passageway is blocked, the higher pressure in the sinus will press on the bones surrounding it to cause a horrible headache. When your nose is stuffy, the inner linings of your nose are swollen, and the same swelling can shut the sinus passageway, preventing air pressure inside your sinus from changing to balance the pressure outside, and you can develop a sinus headache.

If your nose is stuffy most of the time and your mucous is clear, you could have an allergy, an irritation from smoking or air pollution or from some unknown cause. If thick yellow-green mucous drips from your nose, you probably have a sinus infection. Your doctor should order a sinus cat scan X ray. If the X ray shows that you have fluid levels in your sinuses, you have sinusitis.

Nobody really knows how to treat sinusitis. Allergy injections are almost always a complete waste of time, unless you get a stuffy nose every spring and fall when the tree, grass and ragweed pollen are in the air. People who have a chronic stuffy noses all year round rarely benefit from allergy shots. Sinus surgery usually is ineffective and costs a lot on money and pain for no benefit whatever. A couple of years ago, a study from the Mayo Clinic showed that people with chronic sinusitis usually carry fungi in their noses, but multiple efforts to treat sinusitis with long-term anti-fungal medications have failed.

A study in Otolaryngology and Head and Neck Surgery showed that long-term low-dose erythromycin therapy helps to control persistent chronic sinusitis after sinus surgery. This study could help the millions of people who go from doctor to doctor for help in treating their chronic stuffy noses, headaches, pressure in their faces and usually thick yellow-green mucous coming from their noses.

Doctors usually prescribe cortisone-type steroids which make a person with sinusitis feel better, but cortisones have never cured anyone and they can cause horrible side effects such as osteoporosis, obesity, diabetes, high blood pressure and so forth. Taking antibiotics for one week almost never cures a sinus infection. Many previous studies show that you have to take antibiotics for a long time to cure sinusitis. What is encouraging about this paper is that the authors treated their patients, each day, for more than a year with 250 mg of Biaxin, a potent erythromycin antibiotic, and 12 out of 17 patients improved dramatically. The doctors checked their patients every three months for a year. After each patient had been treated with Biaxin for one year, their saccharine transit time, a measure of mucociliary transport, improved. This test measures the ability of the cilia lining their noses to clear mucous and pollution from the nose. Also an endoscopic nasal examination showed that there was marked improvement in the linings of their noses. They also had an improvement in being less stuffy, clearing their sticky secretions faster, and having far less mucous dripping from their noses. They also had far fewer and less severe headaches. The researchers said, “The present study suggests that long-term, low-dose treatment with erythromycin antibiotics is effective in persistent chronic sinusitis that does not respond to sinus surgery or systemic steroid/antibiotic treatment.” However, this treatment is controversial and is not accepted by most doctors. Discuss it with your doctor.

Usually symptoms start with coughing and sneezing, and you feel tired and achy. Most people thing they are just getting a cold. When over the counter meds stop working, and you develop a terrible headache, you eventually you drag yourself in to see the doctor. After listening to your history of symptoms, examining your face and forehead, and perhaps doing a sinus X-ray, the doctor says you have sinusitis.

Sinusitis simply means inflammation of the sinuses, but this gives little indication of the misery and pain this condition can cause. Chronic sinusitis, sinusitis that persists for at least 3 weeks, affects an estimated 32 million people in the United States. Americans spend millions of dollars each year for medications that promise relief from their sinus symptoms.

Sinuses are hollow air spaces, of which there are many in the human body. These cavities, located within the skull or bones of the head surrounding the nose, include the frontal sinuses over the eyes in the brow area; the maxillary sinuses inside each cheekbone; the ethmoids just behind the bridge of the nose and between the eyes; and behind them, the sphenoids in the upper region of the nose and behind the eyes.

Each sinus has an opening into the nose for the free exchange of air and mucus, and each is joined with the nasal passages by a continuous mucous membrane lining. Therefore, anything that causes a swelling in the nose – an infection or an allergic reaction – also can affect the sinuses. Air trapped within an obstructed sinus, along with pus or other secretions, may cause pressure on the sinus wall. The result is the sometimes intense pain of a sinus attack. Similarly, when air is prevented from entering a paranasal sinus by a swollen membrane at the opening, a vacuum can be created that also causes pain.

Sinusitis has its own localized pain signals, depending upon the particular sinus affected. Headache upon awakening in the morning is characteristic of sinus involvement. Pain when the forehead over the frontal sinuses is touched may indicate inflammation of the frontal sinuses. Infection in the maxillary sinuses can cause the upper jaw and teeth to ache and the cheeks to become tender to the touch. Since the ethmoid sinuses are near the tear ducts in the corner of the eyes, inflammation of these cavities often causes swelling of the eyelids and tissues around the eyes, and pain between the eyes.

Other symptoms of sinusitis can include fever, weakness, tiredness, a cough that may be more severe at night, and runny nose or nasal congestion. In addition, drainage of mucus from the sphenoids (or other sinuses) down the back of the throat (postnasal drip) can cause a sore throat and can irritate the membranes lining the larynx (upper windpipe). On rare occasions, acute sinusitis can result in brain infection and serious complications.

Most cases of acute sinusitis are preceded by virus-induced “colds.” These viral “colds” do not cause symptoms of sinusitis, but they do cause inflammation of the sinuses. Both the “cold” and the sinus inflammation usually resolve without treatment in two weeks. However, the inflammation might explain why colds increase the likelihood of developing acute sinusitis. For example, the nose reacts to an invasion by viruses that cause infections such as the common cold, flu, or measles by producing mucus and sending white blood cells to the lining of the nose, which congest and swell the nasal passages. When this swelling involves the adjacent mucous membranes of the sinuses, air and mucus are trapped behind the narrowed openings of the sinuses. If the sinus openings become too narrow to permit drainage of the mucus, then bacteria, which normally are present in the respiratory tract, begin to multiply. Most healthy people harbor bacteria, such as Streptococcus pneumoniae and Haemophilus influenzae, in their upper respiratory tracts with no ill effects until the body’s defenses are weakened or drainage from the sinuses is blocked by a cold or other viral infection. The bacteria that may have been living harmlessly in the nose or throat can multiply and cause an acute sinus infection.

Sometimes, fungal infections can cause acute sinusitis. Although these organisms are abundant in the environment, they usually are harmless to healthy people, indicating that the human body has a natural resistance to them. Fungi, such as Aspergillus, can cause serious illness in people whose immune systems are not functioning properly. Some people with fungal sinusitis have an allergic-type reaction to the fungi.

Chronic inflammation of the nasal passages (rhinitis) also can lead to sinusitis. Allergic rhinitis or hay fever (discussed below) may be complicated by episodes of acute sinusitis. Patients with allergic rhinitis also often have chronic sinusitis. Vasomotor rhinitis, caused by humidity, cold air, alcohol, perfumes, and other environmental conditions, also may be complicated by sinus infections.

Patients with asthma have a particularly high frequency of chronic sinusitis. Inhalation of airborne allergens (substances that provoke an allergic reaction), such as dust, mold, and pollen, often set off allergic reactions (allergic rhinitis) that, in turn, may contribute to sinusitis. People who are allergic to fungi can develop a condition called “allergic fungal sinusitis.”

Allergies
A runny nose, itchy eyes, sore or scratchy throat, uncontrollable sneezing and sometimes itching of the skin are all symptoms of what is commonly called hay fever. Yet these symptoms are not caused by hay, and do not produce a fever. The correct name for the condition is seasonal allergic rhinitis. Seasonal allergic rhinitis occurs when airborne pollutants (such as pollen, animal dander, mold spores, etc.) come into contact with the lining of the nose, eyes, or throat.

The immune system normally protects the body against harmful substances such as bacteria, viruses, and toxins. Sometimes, however, the immune system mistakenly tries to protect against a harmless substance, and in the process, causes an allergic reaction. Many substances, or allergens, that can trigger allergies. Allergens that are known to trigger nasal allergies include pollens, animal dander, molds and dust mites, among others. In the United States, the most prevalent pollen comes from ragweed. It begins pollinating in late August and continues until the first frost.

When pollen triggers an allergic reaction, the condition is referred to as hay fever, seasonal allergic rhinitis, or pollinosis. If you have hay fever, you are not alone. An estimated 26.1 million Americans experience hay fever symptoms each year. In addition, 14.6 million Americans have asthma, which often accompanies hay fever.

The immune system normally protects the body against harmful substances such as bacteria, viruses, and toxins. Sometimes, however, the immune system mistakenly tries to protect against a harmless substance, and in the process, causes an allergic reaction. There are many such substances, or allergens, that can trigger allergies. Allergens that are known to trigger nasal allergies include pollens, cat dander, molds and dust mites, among others.

If you suffer from severe or chronic sinus-related allergies, if your symptoms do not respond to allergy medications, or if you are symptomatic more than six months a year, your physician may prescribe immunotherapy. Immunotherapy, or allergy shots, is a treatment for allergic reactions to grass pollens, dust mites and other known allergens. It is the only therapeutic treatment that has the potential to cure allergies.

The first step in the immunotherapy process is to screen for allergens. Your physician will ask for a thorough medical history and then administer tests to help identify your specific allergens. Skin tests (either prick or intradermal dilutional testing) are slightly more sensitive than blood tests (RAST, ELIZA, etc.).

Afterwards, you will be given increasing doses of the allergens to which you are allergic. Incremental doses administered over time prompt the immune system to become less and less sensitive to these allergens. Besides easing or eliminating allergic reactions, immunotherapy also reduces the chronic inflammation that characterizes rhinitis (nasal inflammation) and asthma.

While you are undergoing immunotherapy, you may also be counseled on ways to reduce allergens in your environment.

Treating Allergy-Related Sinusitis

What can help allergy-related sinus symptoms is irrigation with saline solution, either with a neti pot or squeeze bottle — if your nasal passages aren’t blocked. Although, there’s no evidence they help with sinus infections, nasal steroid sprays may help some people suffering sinus symptoms from allergies.

Antihistamines may help, too, especially for symptoms of sneezing and runny nose.

Sinusitis Quiz

Sinusitis is an inflammation of the lining membrane of any sinus. Take the following quiz to see if you have sinusitis.


Choose “yes” if you have any of the following symptoms for ten days or longer; otherwise, choose “no.”

1. Do you have facial pressure/pain?
Yes
No

2. Do you have headache pain?
Yes
No

3. Do you have congestion or a stuffy nose?
Yes
No

4. Do you have thick, yellow-green nasal discharge?
Yes
No

5. Do you have a low fever (99ºF – 100ºF)?
Yes
No

6. Do you have bad breath?
Yes
No

7. Do you have pain in the upper teeth?
Yes
No

If you answered yes to 3 or more questions, you may have sinusitis and should contact an ENT physician.


Biodegradable Particles Can Bypass Mucus, Release Drugs Over Time
ScienceDaily (Jan. 6, 2010) — Johns Hopkins University researchers have created biodegradable nanosized particles that can easily slip through the body’s sticky and viscous mucus secretions to deliver a sustained-release medication cargo.

The researchers say these nanoparticles, which degrade over time into harmless components, could one day carry life-saving drugs to patients suffering from dozens of health conditions, including diseases of the eye, lung, gut or female reproductive tract.

The mucus-penetrating biodegradable nanoparticles were developed by an interdisciplinary team led by Justin Hanes, a professor of chemical and biomolecular engineering in the Whiting School of Engineering at Johns Hopkins. The team’s work was reported recently in the Proceedings of the National Academy of Sciences. Hanes’ collaborators included cystic fibrosis expert Pamela Zeitlin, a professor of pediatrics at the Johns Hopkins School of Medicine and director of pediatric pulmonary medicine at the Johns Hopkins Children’s Center.

These nanoparticles, Zeitlin said, could be an ideal means of delivering drugs to people with cystic fibrosis, a disease that kills children and adults by altering the mucus barriers in the lung and gut.

“Cystic fibrosis mucus is notoriously thick and sticky and represents a huge barrier to aerosolized drug delivery,” she said. “In our study, the nanoparticles were engineered to travel through cystic fibrosis mucus at a much greater velocity than ever before, thereby improving drug delivery. This work is critically important to moving forward with the next generation of small molecule and gene-based therapies.”

Beyond their potential applications for cystic fibrosis patients, the nanoparticles also could be used to help treat disorders such as lung and cervical cancer, and inflammation of the sinuses, eyes, lungs and gastrointestinal tract, said Benjamin C. Tang, lead author of the recent journal article and a postdoctoral fellow in the Department of Chemical and Biomolecular Engineering.

“Chemotherapy is typically given to the whole body and has many undesired side effects,” he said. “If drugs are encapsulated in these nanoparticles and inhaled directly into the lungs of lung cancer patients, drugs may reach lung tumors more effectively, and improved outcomes may be achieved, especially for patients diagnosed with early stage non-small cell lung cancer.”

In the lungs, eyes, gastrointestinal tract and other areas, the human body produces layers of mucus to protect sensitive tissue. But an undesirable side effect is that these mucus barriers can also keep helpful medications away.

In proof-of-concept experiments, previous research teams led by Hanes earlier demonstrated that latex particles coated with polyethylene glycol could slip past mucus coatings. But latex particles are not a practical material for delivering medication to human patients because they are not broken down by the body. In the new study, the researchers described how they took an important step forward in making new particles that biodegrade into harmless components while delivering their drug payload over time.

“The major advance here is that we were able make biodegradable nanoparticles that can rapidly penetrate thick and sticky mucus secretions, and that these particles can transport a wide range of therapeutic molecules, from small molecules such as chemotherapeutics and steroids to macromolecules such as proteins and nucleic acids,” Hanes said. “Previously, we could not get these kinds of sustained-release treatments through the body’s sticky mucus layers effectively.”

The new biodegradable particles comprise two parts made of molecules routinely used in existing medications. An inner core, composed largely of polysebacic acid (PSA), traps therapeutic agents inside. A particularly dense outer coating of polyethylene glycol (PEG) molecules, which are linked to PSA, allows a particle to move through mucus nearly as easily as if it were moving through water and also permits the drug to remain in contact with affected tissues for an extended period of time.

In Hanes’ previous studies with mucus-penetrating particles, latex particles could be effectively coated with PEG but could not release drugs or biodegrade. Unlike latex, however, PSA can degrade into naturally occurring molecules that are broken down and flushed away by the body through the kidney, for example. As the particles break down, the drugs loaded inside are released.

This property of PSA enables the sustained release of drugs, said Samuel Lai, assistant research professor in the Department of Chemical and Biomolecular Engineering, while designing them for mucus penetration allows them to more readily reach inaccessible tissues.

Jie Fu, an assistant research professor, also from the Department of Chemical and Biomolecular Engineering, said, “As it degrades, the PSA comes off along with the drug over a controlled amount of time that can reach days to weeks.”

Polyethylene glycol acts as a shield to protect the particles from interacting with proteins in mucus that would cause them to be cleared before releasing their contents. In a related research report, the group showed that the particles can efficiently encapsulate several chemotherapeutics, and that a single dose of drug-loaded particles was able to limit tumor growth in a mouse model of lung cancer for up to 20 days.

Hanes, Zeitlin, Lai and Fu are all affiliated with Johns Hopkins Institute for NanoBioTechnology. Other authors on the paper are Ying-Ying Wang, Jung Soo Suk, and Ming Yang, doctoral students in the Johns Hopkins Department of Biomedical Engineering; Michael P. Boyle, an associate professor in Pulmonary and Critical Care Medicine at the Johns Hopkins School of Medicine; and Michelle Dawson, an assistant professor at the Georgia Institute of Technology.

This work was supported in part by funding from the National Institutes of Health, a National Center for Research Resources Clinical and Translational Science Award, the Cystic Fibrosis Foundation, the National Science Foundation and a Croucher Foundation Fellowship.

The technology described in the journal article is protected by patents managed by the Johns Hopkins Technology Transfer office and is licensed exclusively by Kala Pharmaceuticals. Justin Hanes is a paid consultant to Kala Pharmaceuticals, a startup company in which he holds equity, and is currently a member of its board. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.


Source: Johns Hopkins University


Journal Reference:

  1. Tang et al. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Proceedings of the National Academy of Sciences, 2009; 106 (46): 19268 DOI: 10.1073/pnas.0905998106

Sleep Apnea:

The Greek word “apnea” literally means “without breath.” There are three types of apnea: obstructive, central, and mixed; of the three, obstructive is the most common. Despite the difference in the root cause of each type, in all three, people with untreated sleep apnea stop breathing repeatedly during their sleep, sometimes hundreds of times during the night and often for a minute or longer.

Obstructive sleep apnea (OSA) is caused by a blockage of the airway, usually when the soft tissue in the rear of the throat collapses and closes during sleep. In central sleep apnea, the airway is not blocked but the brain fails to signal the muscles to breathe. Mixed apnea, as the name implies, is a combination of the two. With each apnea event, the brain briefly arouses people with sleep apnea in order for them to resume breathing, but consequently sleep is extremely fragmented and of poor quality.

Sleep apnea is very common, as common as adult diabetes, and affects more than twelve million Americans, according to the National Institutes of Health. Risk factors include being male, overweight, and over the age of forty, but sleep apnea can strike anyone at any age, even children. Yet still because of the lack of awareness by the public and healthcare professionals, the vast majority remain undiagnosed and therefore untreated, despite the fact that this serious disorder can have significant consequences.

Untreated, sleep apnea can cause high blood pressure and other cardiovascular disease, memory problems, weight gain, impotency, and headaches. Moreover, untreated sleep apnea may be responsible for job impairment and motor vehicle crashes. Fortunately, sleep apnea can be diagnosed and treated. Several treatment options exist, and research into additional options continues.

Definition:  tumor marker 

A substance that may be found in tumor tissue or released from a tumor into the blood or other body fluids. A high level of a tumor marker may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (in ovarian cancer), CA 15-3 (in breast cancer), CEA (in ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (in prostate cancer).  www.cancer.gov

Tumor Markers – This microscopic image is Celladhesion proteins.
The atypical localization of ß-catenin in benign early stages of a human colon tumor is shown in yellow. Normally, this protein is found only at cell boundaries. If it is found also in the core of individual tumor cells it develops new properties. This is a start signal for the transformation of a benign tumor into malignant carcinoma. 
Photo credit: Max Planck Institute for Molecular Physiology

Tumor Markers


What are they? | Why done? | Table of Markers | Related Pages

What are they?

Tumor markers are substances, usually proteins, that are produced by the body in response to cancer growth or by the cancer tissue itself and that may be detected in blood, urine, or tissue samples. Some tumor markers are specific for a particular type of cancer, while others are seen in several cancer types. Most of the well-known markers may also be elevated in non-cancerous conditions. Consequently, tumor markers alone are not diagnostic for cancer.

There are only a handful of well-established tumor markers that are routinely used by physicians. Many other potential markers are still being researched. Some markers cause great excitement when they are first discovered but, upon further investigation, prove to be no more useful than markers already in use.

The goal is to be able to screen for and diagnose cancer early, when it is the most treatable and before it has had a chance to grow and spread. One tumor marker to gain wide acceptance as a screening test is Prostate Specific Antigen (PSA) for prostate cancer in men. Even with PSA there is continued debate among experts and national organizations over the usefulness of this test for screening asymptomatic men. Other markers are either not specific enough (too many false positives, leading to expensive and unnecessary follow-up testing) or they are not elevated early enough in the disease process to be useful for screening.

Some people are at a higher risk for particular cancers because they have inherited a genetic mutation. While not considered tumor makers, there are tests that look for these mutations in order to estimate the risk of developing a particular type of cancer. BRCA1 and BRCA2 are examples of gene mutations related to an inherited risk of breast cancer and ovarian cancer. For more information, see our overview on genetic testing.

Blood tests are used to look for hCG tumor markers.

Injection with Blood 3 image by Svenja98 from Fotolia.com

More than 12 different tumor markers have been identified, as different types of tumors will produce different substances. One such marker is human Chorionic Gonadotropin, or hCG.

Why are they done?

Tumor markers are not diagnostic in themselves. A definitive diagnosis of cancer is made by looking at tissue biopsy specimens under a microscope. However, tumor markers provide information that can be used to:

  • Screen. Most markers are not suited for general screening, but some may be used in people with a strong family history of a particular cancer. As mentioned, PSA testing may be used to screen for prostate cancer.
  • Diagnose. In a person who has symptoms, tumor markers may be used to help identify the source of the cancer, such as CA-125 for ovarian cancer, and to help differentiate it from other conditions. Remember that tumor markers cannot diagnose cancer by themselves but aid in this process.
  • Stage. If a person does have cancer, tumor marker elevations can be used to help determine how far the cancer has spread into other tissues and organs.
  • Determine Prognosis. Some tumor markers can be used to help doctors determine how aggressive a cancer is likely to be.
  • Guide Treatment. A few tumor markers, such as Her2/neu, will give doctors information about what treatments their patients may respond to (for instance, breast cancer patients who are Her2/neu positive are more likely to respond to Herceptin treatment).
  • Monitor Treatment. Tumor markers can be used to monitor the effectiveness of treatment, especially in advanced cancers. If the marker level drops, the treatment is working; if it stays elevated, adjustments are needed. The information must be used with care, however, since other conditions can sometimes cause tumor markers to rise or fall.
  • Determine Recurrence. Currently, one of the most important uses for tumor markers is to monitor for cancer recurrence. If a tumor marker is elevated before treatment, low after treatment, and then begins to rise over time, then it is likely that the cancer is returning. (If it remains elevated after surgery, then chances are that not all of the cancer was removed.)

 

Common Tumor Markers Currently in Use

tumor markers cancers What else? When/how used Usual sample
AFP (Alpha-feto protein) Liver, germ cell cancer of ovaries or testes Also elevated during pregnancy Help diagnose, monitor treatment, and determine recurrence Blood
B2M (Beta-2 microglobulin) Multiple myeloma
and lymphomas
Present in many other conditions, including Crohn’s disease and hepatitis; often used to determine cause of renal failure Determine prognosis Blood
CA 15-3 (Cancer antigen 15-3) Breast cancer and others, including lung, ovarian Also elevated in benign breast conditions; doctor can use CA 15-3 or CA 27.29 (two different assays for same marker) Stage disease, monitor treatment, and determine recurrence Blood
CA 19-9 (Cancer antigen 19-9) Pancreatic, sometimes colorectal and bile ducts Also elevated in pancreatitis and inflammatory bowel disease Stage disease, monitor treatment, and determine recurrence Blood
CA-125 (Cancer antigen 125) Ovarian Also elevated with endometriosis, some other benign diseases and conditions; not recommended as a general screen Help diagnose, monitor treatment, and determine recurrence Blood
Calcitonin Thyroid medullary carcinoma Also elevated in pernicious anemia and thyroiditis Help diagnose, monitor treatment, and determine recurrence Blood
CEA (Carcino-embryonic antigen) Colorectal, lung,
breast, thyroid, pancreatic, liver, cervix, and bladder
Elevated in other conditions such as hepatitis, COPD, colitis, pancreatitis, and in cigarette smokers Monitor treatment and determine recurrence Blood
Chromogranin A (CgA) Neuroendocrine tumors (carcinoid tumors, neuroblastoma) May be most sensitive tumor marker for carcinoid tumors To help diagnose and monitor Blood
Estrogen receptors Breast Increased in hormone-dependent cancer Determine prognosis and guide treatment Tissue
hCG (Human chorionic gonadotropin) Testicular and trophoblastic disease Elevated in pregnancy, testicular failure Help diagnose, monitor treatment, and determine recurrence Blood, urine
Her-2/neu Breast Oncogene that is present in multiple copies in 20-30% of invasive breast cancer Determine prognosis and guide treatment Tissue
Monoclonal immunoglobulins Multiple myeloma and Waldenstrom’s macroglobulinemia Overproduction of an immunoglobulin or antibody, usually detected by protein electrophoresis Help diagnose,
monitor treatment, and determine recurrence
Blood, urine
Progesterone receptors Breast Increased in hormone-dependent cancer Determine prognosis and guide treatment Tissue
PSA (Prostate specific antigen), total and free Prostate Elevated in benign prostatic hyperplasia, prostatitis and with age Screen for and help diagnose, monitor treatment, and determine recurrence Blood
Thyroglobulin Thyroid Used after thyroid is removed to evaluate treatment Determine recurrence Blood
Other Tumor Markers Less Widely Used        
BTA (Bladder tumor antigen) Bladder Not widely available, but gaining acceptance Help diagnose and determine recurrence Urine
CA 72-4 (Cancer antigen 72-4) Ovarian No evidence that it is better than CA-125 but may be useful when combined with it; still being studied Help diagnose Blood
Des-gamma-carboxy prothrombin (DCP) Hepatocellular carcinoma (HCC) New test; often used along with an imaging study plus AFP and/or AFP-L3% to evaluate if someone with chronic liver disease has developed HCC To evaluate risk of developing HCC; to evaluate treatment; to monitor for recurrence  Blood
EGFR (Her-1) Solid tumors, such as of the lung (non small cell), head and neck, colon, pancreas, or breast Not available in every laboratory Guide treatment and determine prognosis Tissue
NSE (Neuron-specific enolase) Neuroblastoma, small cell lung cancer May be better than CEA for following this particular kind of lung cancer Monitor treatment Blood
 NMP22 Bladder  Not widely used Help diagnose and determine recurrence  Urine
Prostate-specific membrane antigen (PSMA)  Prostate Not widely used; levels increase normally with age  Help diagnose  Blood
Prostatic acid phosphatase (PAP) Metastatic prostate cancer, myeloma, lung cancer Not widely used anymore; elevated in prostatitis and other conditions Help diagnose  Blood
 S-100 Metastatic melanoma  Not widely used Help diagnose  Blood
Soluble Mesothelin-Related Peptides (SMRP) Mesothelioma  Often used in conjunction with imaging tests To monitor progression or recurrence  Blood
 TA-90 Metastatic melanoma  Not widely used, being studied  Help diagnose  Blood

© 2001 – 2009 by American Association for Clinical Chemistry

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Tumor markers can be produced directly by the tumor or by non-tumor cells as a response to the presence of a tumor.

Koepke outlines a hierarchy of clinical laboratory tests, from least to most informative. As used in oncology, they are as follows:

  • Screening for common cancers on a population basis

Example: elevated prostate specific antigen suggests prostate cancer.

  • Monitoring of cancer survivors after treatment

Example: elevated AFP in a child previously treated for teratoma suggests relapse with endodermal sinus tumor.

  • Diagnosis of specific tumor types, particularly in certain brain tumors and other instances where biopsy is not feasible.

The term tumor antigen is sometimes interchangeably used for tumor marker.

Classification

Tumor markers can be classified in two groups: Cancer-specific markers and tissue-specific markers.

Cancer-specific markers

Cancer-specific markers are related to the presence of certain cancerous tissue. Because there is a large overlap between the many different tumor tissue types and the markers produced these markers might not be specific in making a diagnosis. They can, however, be useful in the follow-up of treated patients to describe progress of the disease or response to treatment. A few examples of these markers are CEA, CA19-9, CA125.

An example of a cancer-specific marker, CEA, or carcinoembryonic antigen, is a blood-borne protein, first noted to be produced by tumors of the gastrointestinal system. Further investigation showed that it was produced by the occasional lung and breast cancer case, meaning that an elevated level does not necessarily mean a bowel cancer. However, in a patient with a history of a treated bowel cancer, a rising CEA level can be an early sign of recurring bowel cancer. This usually occurs before the site of return can be identified on imaging or examination and so many oncologists question the wisdom of doing a blood test for CEA when the end result is bad news that alarms the patient. Nevertheless, a sequence of steady low CEA readings can provide much needed reassurance to the post-operative patient. Also, a rising sequence of CEA readings should alert the physician to the need for diagnostic tests such as PET scans.

Tissue-specific markers

Tissue-specific markers are related to specific tissues which have developed cancer. Generally speaking, these substances are not specifically related to the tumor, and may be present at elevated levels when no cancer is present. But unlike the previous group, elevated levels point to a specific tissue being at fault. Examples include PSA, beta-HCG – (Human chorionic gonadotropin), AFP – (Alpha-fetoprotein), AFP-L3 – (a lectin-reactive AFP) and Thyroglobulin. For example, if a man has an elevated PSA, a search for prostate cancer will be undertaken. If an individual has an elevated level of beta-HCG, AFP or AFP-L3%, a search for a testicular or liver cancer, respectively, will be made.

PSA (Prostate specific antigen) is produced by the normal prostate. It is a protein enzyme called a serine protease that usually acts as an anticoagulant to keep semen liquid. Only small amounts leak into the circulation in normal circumstances. Enlarged prostates leak more substantial amounts, and cancerous prostates also leak substantial amounts. An accurate way to tell if an elevated PSA level results from cancer is to biopsy the prostate.

β-hCG: Elevated levels cannot prove the presence of a tumor, and low levels do not rule it out (an exception is in males who do not naturally produce β-hCG). Nevertheless, elevated βhCG levels fall after successful treatment (e.g. surgical intervention or chemotherapy), and a recurrence can often be detected by the finding of rising levels.

CA15-3: Elevated CA15-3, in conjunction with alkaline phosphatase, was shown to increase chances of early recurrence in breast cancer.

Application and Interpretation

The high dose hook effect is an artefact of tumor marker immunoassay kits, that causes the reported quantity of tumor marker to be incorrectly low when the quantity is high. An undetected hook effect may cause delayed recognition of a tumor.  The hook effect can be detected by analyzing serial dilutions. Absent hook effect, reported quantities of tumor marker in a serial dilution should be proportional to the dilution.

If repeated measurements of tumor marker are needed, some clinical testing laboratories provide a special reporting mechanism, a serial monitor, that links test results and other data pertaining to the person being tested. This requires a unique identifier for the person. In the United States commonly a Social Security number & Civil Personal Record (CPR) in Bahrain are used for this. One important function of this mechanism is to ensure that each test is performed using the same assay kit. For example, for AFP many different commercial assay kits, based on different technologies, are available. AFP measurements obtained using different assay kits are not comparable unless special calculations are performed.

Interlaboratory proficiency testing for tumor marker tests, and for clinical tests more generally, is an emerging field.  In the United States, New York state is prominent in advocating such research.

The use of the marker tumor concept in Ta, T1 bladder cancer: Is it justified?

Adrian P.M. van der Meijden, Ph.D.

Abstract 

Adjuvant instillations with chemo- or immunotherapy agents after transurethral resection of Ta, T1 bladder tumors are administered on non-measurable non-visible disease. To know whether adjuvant therapies are efficacious the marker tumor concept has been developed. The use of marker lesions has been questioned by many as dangerous and/or unethical because a deliberately left-behind tumor might be invasive or become invasive if the adjuvant therapy is not effective. However, 4 EORTC, 2 British, and one Japanese study using different drugs have shown that it is safe and ethically justified to use the marker tumor concept in clinical phase II studies. Data from six trials indicate the the risk of leaving an invasive tumor behind or that a tumor might progress while being treated with instillations is 0.8% (3/383). Marker lesion studies should be limited to intermediate risk patients. Expensive and inefficient long term phase III trials may be avoided by marker tumor trials. Exposing patients to ineffective drugs in prophylactic trials also jeopardizes the patient with regard to recurrence and/or progression of their bladder tumors. 

Two of the key contributors to the Johns Hopkins mucus mesh study were Ying-Ying Wang, a biomedical engineering doctoral student, and Samuel Lai, an assistant research professor in the Department of Chemical and Biomolecular Engineering. (Credit: Photo by Will Kirk)

ScienceDaily  — A net with large holes won’t catch small fish. Likewise, the microscopic fibers in the protective mucus coatings of the eyes, lungs, stomach or reproductive system naturally bundle together and allow the tiniest disease-causing bugs, allergens or pollutants to slip by. But Johns Hopkins researchers have discovered a way to chemically shrink the holes in the mucus layer’s netting so that it will keep out more of the unwanted particles.

“The mucus layer is an outstanding barrier to most things, but not a perfect one for objects smaller than several hundred nanometers [about 1,000 times smaller than the width a human hair]. We still get sick far too often,” says Samuel Lai, a chemical and biomolecular researcher in the Whiting School of Engineering and a member of the university’s Institute for NanoBioTechnology (INBT).

“The question we asked was, Can we shrink the size of the holes in the human mucus barrier to help prevent its penetration by potentially harmful nano-size objects?” says Justin Hanes, principal investigator of the study and a professor of chemical and biomolecular engineering. Hanes also is director of therapeutics for the INBT.

The team showed that tiny strands in the mucus layer — the mucin fibers — naturally tend to bundle and bunch together, creating gaps large enough for pathogens and potentially dangerous pollutants to get in. But by adding a simple detergent to the mix, Lai and his colleagues partially disrupted the bundling of mucin fibers, a procedure that decreased the size of the holes in the mesh. Particles in the range of 200 nanometers in diameter that previously slipped through easily now became trapped in the more finely strung netting.

For this research, the team studied protective coatings taken from the female reproductive tract, conducting high- resolution microscopy experiments with particles as large as 1 micron and as small as 100 nanometers in size.

To shrink the holes in the network’s mesh, the researchers used a detergent commonly found in many personal care products. Mucus treated with the detergent slowed nanoparticle movement dramatically, especially in the 200- 500 nanometer range, which was clearly demonstrated in videos enhanced by fluorescent imaging.

“We suspected the fibers are bundled together, making large holes in the mucus mesh, but this was the first time it was shown definitively,” says Ying-Ying Wang, a doctoral student and National Science Foundation graduate fellowship recipient in biomedical engineering. “And we didn’t know going into this study exactly how much we could shrink the holes, if at all. It was exciting to see particles the size of many potentially dangerous substances become completely trapped in mucus, since mucus-trapping typically leads to harmless removal from our bodies,” Wang adds.

The team, which also includes Richard Cone, a biophysics professor and INBT-affiliated faculty member from the Krieger School of Arts and Sciences, and Denis Wirtz, professor of chemical and biomolecular engineering and INBT’s associate director, envisions many potential applications for this concept.

“If there is an outbreak of influenza, for example, we imagine that doctors and nurses could inhale these agents in an aerosolized form and be protected against the virus for several hours,” Lai says. “People who work where there are high levels of nanoparticles in the air, such as mine workers or builders, could use a product with these fiber debundling detergents to prevent dangerous exposure.”

Since the mucus layer constantly clears from the body, any enhancement to its protective ability would be short-lived, adds Lai. For example, coatings clear from the lungs in as little as 30 minutes, while the mucus lining in the stomach and intestine takes several hours to renew. This study is only a start, Lai explains, and the technique has not yet been tested in humans. “The next step will be to try different substances, perhaps those paired to specific pathogens, and observe how these substances improve the performance of the mucus barrier,” he says. In addition, microbe-killing agents could be combined with detergents to not only slow but destroy the trapped potential pathogens, he says. Animal studies are being planned.

This work was funded by the National Institutes of Health and a graduate research fellowship from the National Science Foundation.


Source:  Johns Hopkins University.