Claudia Casini Raggi¹, Maria Letizia Bagnoni¹, Gian Paolo Tonini³, Mario Maggi², Giovanna Vona¹, Pamela Pinzani¹, Katia Mazzocco³, Bruno De Bernardi⁴, Mario Pazzagli¹ and Claudio Orlando^1,a

1.        Clinical Biochemistry

2.        Andrology Units, Department of Clinical Physiopathology, University of Florence, 50139 Florence, Italy.

3.        Unit of Solid Tumor Biology, Advanced Biotechnology Centre

4.        Giannina Gaslini Children’s Hospital, 16132 Genoa, Italy.

Background: Neuroblastoma is the most common extracranial malignant solid tumor in children under 5 years and is characterized by a wide clinical and biological heterogeneity, from spontaneously regressive forms to cancers with a rapid and fatal progression. MYCN oncogene amplification is considered the most important prognostic factor to evaluate survival and therapeutic choices in these patients.

Methods: Here we present a new assay for rapid and accurate measurement of MYCN amplification, based on real-time quantitative PCR with the TaqMan^TM reaction. The degree of MYCN amplification was derived from the ratio of the MYCN oncogene and the single-copy reference gene, ß-actin. The absolute abundance of these two genes in tumor sample DNA was obtained by extrapolation on external calibration curves generated with reference DNA.

Results: We found a variable degree of MYCN amplification, from 2 to 29, in 26 of 49 (53%) neuroblastomas. These results were well correlated to those obtained with a competitive PCR assay in the same samples (r = 0.987). MYCN amplification was associated mainly with advanced cancer stages, and the analysis of overall survival confirmed that the measurement of MYCN amplification is a predictor of patient outcome in neuroblastoma. Patients without MYCN amplification had a cumulative survival significantly higher than patients with low (<9; P = 0.02) and high (9; P = 0.03) oncogene amplification.

Conclusion: The assay is rapid and reproducible and does not require any post-PCR analytical procedure.

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PACIFIC CITY (AP) — Dream homes, naturally, begin with dreams. In this one, fund-raisers dreamed of donors with deep pockets. Landowners dreamed of sharing their good fortune. Architects dreamed of uplifting ambiance. Townspeople dreamed of being top-notch neighbors.

And the parents of a small but powerful girl wondered — loud enough for fund-raisers, landowners, architects and townspeople to hear — whether, one day, families like theirs might make indelible memories spending time away together in a dream home unlike any other retreat in the West.

All that, though, is history: pie-in-the-sky stuff that Cliff and Regina Ellis tossed around a decade ago.

Today, their dream is all shingles and glass and stone, all angles and light — and it’s almost ready for families with critically ill children to occupy.

The Ellises, who founded the nonprofit Children’s Cancer Association 10 years ago, call their dream home the Caring Cabin. They expect that this month, the first families will begin using the nearly $1.2 million getaway, offered to them at no cost.

Alexandra Ellis insisted on leaving the doors to her rooms open, so that other children at Doernbecher and Legacy Emanuel children’s hospitals could join her tea parties. She’d make friends in a snap and invite them home just as quickly.

Long-legged, blue-eyed and blonde, before she lost her hair, Alex fought neuroblastoma, cancer that attacks the nervous system. Sick for nearly half her short life, she endured surgeries, radiation and chemotherapy. Generations of her family were at her bedside when she died on May 7, 1995, at home in Southwest Portland.

Alex was 5 years old.

A few weeks later, Cliff and Regina Ellis took a cue from their daughter. They invited family, friends and a few folks they barely knew for dinner. Pasta filled plates. Wine spilled into glasses. And a question was served:

“How,’’ Regina Ellis remembers asking her guests, “can we help other families who have to get through this?’’

Clare Hamill was at the Ellises’ dinner table that evening.

Hamill was the Nike executive — today the company’s vice president of new business development — who’d heard through an acquaintance about a little girl with a big wish: Before she died, Alex Ellis wanted to swim with dolphins in Hawaii.

Struggling to pay their daughter’s medical bills, Alex’s parents couldn’t afford to make that one dream come true. But Hamill, who had a 3-year-old daughter of her own, found that in her heart, she couldn’t afford not to.

She dialed Nike colleagues and other connections, and arranged for flights, a hotel and a rental car. Hamill met Regina Ellis for the first time the day she delivered the tickets to the family’s home.

“It makes you realize,’’ Hamill says, “that you can make such a big difference by just saying, ‘Yes.’’’

Caring for a critically sick child, the Ellises had learned which parts of the medical system worked smoothly and which didn’t for families such as theirs. They’d discovered the gaps in social services. They’d felt the exhaustion that accompanies rounds of treatment and relapses.

They learned, too, how much it meant when friends offered mountain cabins or beach houses, so their family could unhook physically and mentally from the intravenous poles and exam rooms and have a couple days, Regina Ellis says, “just to exhale.’’

So when the Ellises proposed starting a foundation to fill in the gaps, including building a retreat for families, Clare Hamill said yes, of course she’d help.

She signed on as the Children’s Cancer Association’s founding president and used her energetic, mile-a-minute style to rally business partners and civic leaders around the fledgling organization.

Paul and Tasca Gulick spotted the query in the Children’s Cancer Association newsletter — the one wondering whether anyone might have land to donate for a respite cabin.

“It just immediately hit us,’’ says Paul Gulick, chief executive officer of Visual Clarity Systems, headquartered in Wilsonville.

The Gulicks owned 24 acres just north of Pacific City in Tillamook County. There, deep woods sheltered a small, placid lake a mile from the beach. Up the hill, a landing would make a picturesque home site.

Now, the Caring Cabin will give families a break from the arduous routines that accompany a child’s grave illness.

Starting on a shoestring budget a decade ago, the Children’s Cancer Association has a $2 million operating budget this year. With a staff of 15 and more than 800 volunteers, the association serves more than 12,000 children and their families each year.

“When you realize what they’ve accomplished,’’ Paul Gulick says, “ … it makes you want to help out any place you can.’’

He and his wife signed over the title to their land.

“We all go about our lives,’’ Bob Thompson says, “taking for granted our health and our families.’’

As he speaks, the design principal at Thompson Vaivoda and Associates Architects Inc. unrolls drawings and spreads them across a table in his downtown Portland office.

Dazzling photographs of the firm’s work adorn the walls. Among the designs are the National Steinbeck Center in Salinas, Calif.; Ericsson’s North American headquarters in Plano, Texas; downtown Portland’s soaring Fox Tower; and the edgy Nike World Campus near Beaverton.

But the drawings on the table are much smaller in scale. They depict 3,900 square feet of polished concrete pillars, open timbers and floor-to-ceiling windows where light and nature itself seem to spill in.

The kitchen opens onto a dining space and living room with a basalt fireplace so beefy that a sizable child could stand in the wood-storage cubbies. Four bedrooms. A game room. A meditation pavilion. Wheelchair-accessible bathrooms, wiring for hospital beds and space for medical oxygen tanks.

The role of the house, says Thompson, who worked on the design with his associate John Heili, is to lift its occupants’ spirits.

In Pacific City, the ideas roll in, says Mary Baggett-Smith, a merchant who leads a committee of townsfolk working to unfurl the welcome mat at the cabin.

Baggett-Smith moved to Pacific City nine years ago, when she retired from teaching. The cabin, she says, has found a town that may be a perfect fit.

“This place brings peace to my soul,’’ she says, “and I think it does to other people, too.’’

In the years since Alex Ellis died, her parents have divorced. They remain partners, though, when it comes to keeping her spirit alive.

Regina Ellis runs the Children’s Cancer Association in Southwest Portland, while Cliff Ellis watches over the cabin construction at the coast. Every few months, when Regina drops by the construction site, “It takes my breath away,’’ she says, “to think of the families who will share it.’’

It takes her breath away, too, when she considers how the power of Alex’s story has opened opportunities and wallets, or, as she puts it, “one spark, fueled by thousands of hearts.’’

“There is no way,’’ she says, “that this project would be opening its doors without the collective effort of hundreds and hundreds of people.’’

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Health & Medicine

—      Colon Cancer

—      Cancer

—      Breast Cancer

Plants & Animals

—      Biology

—      Biotechnology

—      Developmental Biology

Reference

—      Tumor suppressor gene

—      Metastasis

—      Antiviral drug

—      Nanomedicine

Normally, the fungus Helminthosporium carbonum leads to reduced harvests for maize farmers. Yet a specific constituent of the pathogen, namely HC-toxin, might be very useful for medicine. The substance is used by scientists as a basis for developing a new anti-cancer drug. HC-toxin acts on enzymes known as histone deacetylases (HDACs), which structure the packaging of the genetic material, or DNA. HDAC enzymes change, among others, the histones — proteins around which the DNA is wrapped. Alterations in the packaging of the genetic material are suspected to cause cancer or promote its spread. Therefore, scientists are studying substances that inhibit HDAC enzymes for their ability to fight malignant tumors.

Among these substances is HC-toxin, which has now been investigated by researchers of the Clinical Cooperation Unit “Pediatric Oncology” at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). They found out that neuroblastoma cells lose several of their cancer-typical properties when under the influence of the substance: They divide less frequently, show less invasive growth and even their outside appearance resembles healthy nerve cells again. These effects were observed to be stronger than with other HDAC inhibitors investigated previously.

The effect of HC-toxin is presumably based, among other things, on the fact that it promotes the function of an important cellular “cancer brake” known as RB signaling pathway. The investigators found out that the cancer brake was much more active in tumors cells that had been treated with HC-toxin than in untreated cells. They plan to conduct further research to determine whether the substance derived from the maize pathogen is suitable for developing a new drug to fight neuroblastoma.

Neuroblastoma is the second most frequent malignant tumor in children. With an average of 150 new cases diagnosed in Germany each year, neuroblastoma constitutes about seven to eight percent of all childhood cancers. Most affected children are in preschool age, one third are diagnosed under one year of age. Although treatment has been improved over the past few years, chances of recovery from advanced stage neuroblastoma continue to be very low. In addition, the drugs being used often cause serious side effects.

Hedwig E. Deubzer, Volker Ehemann, Frank Westermann, Ralf Heinrich, Gunhild Mechtersheimer, Andreas E. Kulozik, Manfred Schwab, Olaf Witt. Histone deacetylase inhibitor Helminthosporium carbonum (HC)-toxin suppresses the malignant phenotype of neuroblastoma cells. International Journal of Cancer, DOI: 10.1002/ijc23295

The task of the Deutsches Krebsforschungszentrum in Heidelberg (German Cancer Research Center, DKFZ) is to systematically investigate the mechanisms of cancer development and to identify cancer risk factors. The results of this basic research are expected to lead to new approaches in the prevention, diagnosis and treatment of cancer. The Center is financed to 90 percent by the Federal Ministry of Education and Research and to 10 percent by the State of Baden-Wuerttemberg. It is a member of the Helmholtz Association of National Research Centers (Helmholtz-Gemeinschaft Deutscher Forschungszentren e.V.).

Adapted from materials provided by Helmholtz Association of German Research Centres, via EurekAlert!, a service of AAAS.

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If your doctor suggests certain cancer screening tests as part of your health care plan, this does not mean he or she thinks you have cancer. Screening tests are done when you have no symptoms. Since decisions about screening can be difficult, you may want to discuss them with your doctor and ask questions about the potential benefits and risks of screening tests and whether they have been proven to decrease the risk of dying from cancer.

If your doctor suspects that you may have cancer, he or she will order certain tests to see whether you do. These are called diagnostic tests. Some tests are used for diagnostic purposes, but are not suitable for screening people who have no symptoms.

Purposes of this summary

The purposes of this summary on neuroblastoma screening are to:

—      Give information on neuroblastoma.

—      Describe neuroblastoma screening methods and what is known about their effectiveness.

You can talk to your doctor or health care professional about cancer screening and whether it would be likely to help you or your child.

Neuroblastoma Screening

Neuroblastoma is a cancer that primarily affects children. It begins in nerve tissue in the neck, chest, abdomen, or pelvis. It usually originates in the abdomen in the tissues of the adrenal gland. By the time it is diagnosed, the cancer often has spread, most commonly to the lymph nodes, liver, lungs, bones, and/or bone marrow.

Risk of neuroblastoma

Neuroblastoma is the most common type of cancer in infants. The number of new cases of neuroblastoma is greatest among children under 1 year of age and decreases rapidly with age. Males are affected slightly more commonly than females.

Anything that increases a person’s chance of developing a disease is called a risk factor. The risk factors for neuroblastoma have not yet been established.

Screening tests for neuroblastoma

Urine samples can be tested for the presence of specific chemicals that are excreted by most patients with neuroblastoma. Most cases of neuroblastoma are diagnosed before 6 months of age.

It is thought that many neuroblastomas are present and detectable at birth. Studies have suggested devising a once-in-a-lifetime screening test, such as those used for screening newborns for noncancerous conditions, such as phenylketonuria. At this time, however, there is no good scientific evidence showing that screening for neuroblastoma leads to a decrease in deaths from the disease.

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Keywords: apoptosis; human neuroblastoma cancer cells; melatonin; SK-N-MC

Document Type: Research article

DOI: 10.1111/j.1600-079X.2006.00342.x

Affiliations: 1: Departamento de Morfología y Biología Celular 2: Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Facultad de Medicina de la Universidad de Oviedo, Oviedo, Spain

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The tumor usually begins in the tissues of the adrenal gland found in the abdomen, but may also begin in nerve tissue in the neck, chest, and/or pelvis. The adrenal glands are positioned on top of the kidneys. These glands secrete hormones and other important substances that are required for normal functions in the body such as the nervous system.

In the US, approximately 650 children are diagnosed with neuroblastoma each year. It is often present at birth, but not detected until the tumor begins to grow and compress the surrounding organs. Most children affected by neuroblastoma have been diagnosed before the age of 5. In rare cases, neuroblastoma can be detected before birth by a fetal ultrasound. It is the most common tumor found in children younger than 1 year of age. For unknown reasons, it occurs slightly more often in males than in females.

Neuroblastoma cancer cells can spread (metastasize) quickly to other areas of the body (i.e., lymph nodes, liver, lungs, bones, central nervous system, and bone marrow). Approximately 70 percent of all children diagnosed with neuroblastoma will have some metastatic disease.

What causes neuroblastoma?

Most neuroblastoma cells have genetic abnormalities involving chromosome #1, where a deletion or rearrangement is found on the short arm of this chromosome. The chromosome abnormality, in turn, causes amplification of an oncogene called n-myc, even though this gene is not located on chromosome #1. The amplification of n-myc causes uncontrolled cell growth. A variety of other chromosome abnormalities may also be present in neuroblastoma.

It is estimated that as many as 20 percent of neuroblastoma cases result from an inherited mutation, followed by a second mutation occurring after birth, which together initiate uncontrolled cell growth. The remainder of the cases occur from two acquired mutations after birth. Because the tumor occurs very early in childhood, it is doubtful that any environmental exposures the child has incurred could be linked to the development of the tumor.

Neuroblastoma is more common in children born with fetal hydantoin syndrome, neurofibromatosis, and Beckwith-Wiedemann syndrome. The exact relationship between these conditions and the disease are not known.

The chance for neuroblastoma to be present in a future sibling of the patient is about 1 percent. If more than one child has neuroblastoma, the chance for reoccurrence increases.

Research is being conducted to determine if maternal exposure to any toxic substances, environmental pollutions, or radiation during pregnancy could have any link to the child developing neuroblastoma.

What are the symptoms of neuroblastoma?

The following are the most common symptoms of neuroblastoma. However, each child may experience symptoms differently. The symptoms of neuroblastoma vary greatly depending on size, location, and spread of the tumor. Symptoms may include:

—      abdominal mass, either felt during an examination or seen as swollen abdomen

—      tumors in the face or head can cause swelling and bruising of the area around the eyes and uncontrolled eye movement

—      compression of kidney or bladder by the tumor may cause changes in urination

—      bone marrow involvement may present as pain, limping, paralysis, or weakness

—      diarrhea may be present; diarrhea is caused by a substance produced by the tumor (vasoactive intestinal peptide, or VIP)

—      fever

—      high blood pressure and increased heart rate may occur depending on location of tumor and the organs the tumor compresses

The symptoms of neuroblastoma may resemble other conditions or medical problems. Always consult your child’s physician for a diagnosis.

How is neuroblastoma diagnosed?

In addition to a complete medical and physical examination, diagnostic procedures for neuroblastoma may include the following:

—      Blood tests - including a complete blood count, blood chemistries, kidney and liver function tests, and a urinalysis.

—      Multiple imaging studies - to evaluate primary tumor and determine extent/location of any metastases, including:

—      Computed tomography scan (Also called a CT or CAT scan.) - a diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general x-rays.

—      Magnetic resonance imaging (MRI) - a diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body.

—      X-ray - a diagnostic test that uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film.

—      Ultrasound (Also called sonography.) - a diagnostic imaging technique that uses high-frequency sound waves and a computer to create images of blood vessels, tissues, and organs. Ultrasounds are used to view internal organs as they function, and to assess blood flow through various vessels.

—      Bone scans - pictures or x-rays taken of the bone after a dye has been injected that is absorbed by bone tissue. These are used to detect tumors and bone abnormalities.

—      Bone marrow aspiration and/or biopsy - a procedure that involves taking a small amount of bone marrow fluid (aspiration) and/or solid bone marrow tissue (called a core biopsy), usually from the hip bones, to be examined for the number, size, and maturity of blood cells and/or abnormal cells.

—      Spinal tap/lumbar puncture - a special needle is placed into the lower back, into the spinal canal. This is the area around the spinal cord. The pressure in the spinal canal and brain can then be measured. A small amount of cerebral spinal fluid (CSF) can be removed and sent for testing to determine if there is an infection or other problems. CSF is the fluid that bathes your child’s brain and spinal cord.

—      Biopsy of primary tumor and/or metastatic lesions

Diagnosing neuroblastoma also involves staging and classifying the disease which determines treatment options and prognosis. Staging is the process of determining whether cancer has spread and, if so, how far. There are various staging systems that can be used for neuroblastoma. Always consult your child’s physician for information on staging. One method of staging neuroblastoma is the following:

—      Stage 1 - involves a tumor that does not cross the midline of the body, is completely resectable, and has not spread to other areas of the body. The lymph nodes on the same side of the body as the tumor do not have cancer cells present.

—      Stage 2A - involves a tumor that does not cross the midline of the body, but is not completely resectable. This stage of tumor has not spread to other areas of the body, and lymph nodes on the same side as the tumor do not have tumor cells present.

—      Stage 2B - involves a tumor that may or may not be completely resectable, has not spread to other areas of the body, but lymph nodes on the same side of the tumor have tumor cells present. Lymph nodes on the opposite side of the tumor must be negative for tumor cells in this stage of disease.

—      Stage 3 - involves a tumor that crosses the midline of the body, is not completely resectable, and lymph nodes are positive for tumor cells. This stage also includes a tumor that does not cross the midline, but the lymph nodes on the opposite side also contain tumor cells.

—      Stage 4 - involves a tumor that has metastasized to distant lymph nodes, bone marrow, liver, skin, and/or other organs (except as defined in stage 4S).

—      Stage 4S - a child is younger than 12 months and has a tumor that may have metastasized (spread) to liver, skin, and/or bone marrow (includes minimal bone marrow involvement; more extensive bone marrow involvement should be classified as stage 4). The tumor is on one side of the body and is localized. It may have spread to the lymph nodes on the same side of the body.

Treatment for neuroblastoma:

Specific treatment for neuroblastoma will be determined by your child’s physician based on:

—      your child’s age, overall health, and medical history

—      extent of the disease

—      your child’s tolerance for specific medications, procedures, or therapies

—      expectations for the course of the disease

—      your opinion or preference

Treatment may include (alone or in combination):

—      Surgery (for tumor and/or metastatic resection, and removal of lymph nodes involved)

—      Chemotherapy

—      Radiation therapy

—      Bone marrow transplant

—      Retinoid therapy

—      Supportive care (for the side effects of treatment)

—      Antibiotics (to prevent/treat infections)

—      Continuous follow-up care (to determine response to treatment, recurrent disease, and late effects of treatment)

Treatment options should be discussed with your child’s physician.

Long-term outlook for a child with neuroblastoma:

Prognosis greatly depends on:

—      The extent of the disease.

—      The size and location of the tumor.

—      A presence or absence of metastasis.

—      The tumor’s response to therapy.

—      The age and overall health of your child.

—      Your child’s tolerance of specific medications, procedures, or therapies.

—      New developments in treatment.

As with any cancer, prognosis and long-term survival can vary greatly from individual to individual. Prompt medical attention and aggressive therapy are important for the best prognosis. Continuous follow-up care is essential for a child diagnosed with neuroblastoma. Side effects of radiation and chemotherapy, as well as recurrence of the disease, can occur in survivors of neuroblastoma. New methods are continually being discovered to improve treatment and to decrease side effects.

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But that didn’t prevent several hundred people from showing up that day to participate in the 14th Annual Jon Callaghan Memorial Turkey Trot 5k Fun Run and Walk Nov. 22.

Sponsored by the Gurnee Police and Fire Departments, the Gurnee Community Church, and Fifth Third Bank, the event allowed walkers and runners to stretch their legs and stomachs for a good cause.

Cmdr. Jim Caldwell, from the Gurnee Police Department, said the event drew a good crowd, which it usually does, even if the weather was chilly.

“It was cold and windy for sure,” Caldwell said.

Because the event was not a sanctioned 5k, Caldwell said, times weren’t tracked for runners, and no prizes were awarded.

“This was strictly for fun,” he said.

Runners and walkers did seem to have fun at the event, as a father and daughter took to the route with construction-paper turkeys on their heads.

Callaghan was a student at O’Plaine School in Gurnee who died in 1997 from neuroblastoma cancer. As the Callaghan family requested, the funds raised have been used to help Make-a-Wish Foundation, Children’s Memorial Hospital Cancer Research, Gurnee Elementary School District 56’s program for learning-disabled students, and many others.

Each year, Gurnee Community Church Youth Work Camp participants raise funds to meet their goal of helping those who are less fortunate by building affordable housing.

Want to help?

Donation checks to the Turkey Trot can be made out to the Gurnee Turkey Trot and mailed to Fifth Third Bank, 7500 Grand Ave., Gurnee, IL 60031, attn: Brian Moy.

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The Cape Breton Post

SYDNEY — At least one element that shapes Ian Burrows is common, his blood type. It’s a biological bonus that gives him comfort while trying to overcome cancer, he says.

“They always had blood for me,” said the 21-year-old Glace Bay resident who has received more than 200 transfusions of A+ blood while undergoing treatments for neuroblastoma cancer. “I can’t imagine having a rare blood type. I’d be frightened for them.”

Burrows attended Tuesday’s grand opening of the Sydney Blood Donor Clinic at 850 Grand Lake Rd. As guest speaker, Burrows shed light on the “heroes” who donated the blood he needed to gather strength to carry through years of treatment.

“They had the kindness to lend their veins so that I could live; so that I could have a chance at beating this disease,” he said. “You never know how important blood donations are until you need blood or know someone who needs it.”

Burrows said neuroblastoma cancer is typically a childhood cancer but his disease didn’t become symptomatic until he was 17 years old. He’s undergone 18 radiation treatments and had his own bone marrow harvested and infused back into his body. The stem cells then started producing new blood cells that helped shrink the tumour that invaded his spinal column.

During his long recovery, Burrows needed daily transfusions of blood to increase his energy.

“It was hard to function when it was low.”

Burrows said his health improved and he was able to graduate from high school and is now a student in Cape Breton University’s nursing program.

Peter MacDonald, regional director at Canadian Blood Services Atlantic, said many Canadians feel blood donations are used to treat trauma victims but there are many patients who need blood daily, including patients undergoing cancer treatment.

MacDonald said about 4.1 per cent of Nova Scotians give blood, a percentage he would like to see increased to about 5 per cent.

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Neurons (nerve cells) are the main component of the brain and spinal cord and of the nerves that connect them to the rest of the body. These cells are essential for thinking, sensation, and movement. There is a part of the nervous system that we are rarely aware of, called the autonomic nervous system, which controls involuntary body functions such as heart rate, blood pressure, and digestion. The sympathetic nervous system is a part of the autonomic nervous system. It includes:

—      nerve fibers that run alongside the spinal cord

—      clusters of nerve cells called ganglia (plural of ganglion) at certain points along the path of the nerve fibers

—      nerve-like cells found in the medulla (center) of the adrenal glands. The adrenals are triangular-shaped glands located above the kidneys. The hormone adrenaline comes from the cells in the adrenal gland.

Most neuroblastomas (about two thirds) start in the abdomen. About one third of neuroblastomas start in the adrenal glands and another third begin in the sympathetic nervous system ganglia of the abdomen. The rest start in sympathetic ganglia of the chest or neck or in the pelvis. Some can start in the spinal cord. Rarely, a neuroblastoma may have spread so extensively by the time it is found that doctors are unable to determine exactly where it started.

Not all childhood autonomic nervous system tumors are malignant (cancerous). There is a benign tumor called ganglioneuroma which is composed of mature ganglion and nerve sheaths that do not continue to grow.

Ganglioneuroblastoma is a tumor that has both malignant and benign parts. It contains neuroblasts (immature nerve cells) that can grow and spread abnormally, as well as areas of benign tissue that are similar to ganglioneuroma.

Ganglioneuromas are usually removed by surgery and carefully examined under a microscope to be certain they do not have areas of ganglioneuroblastoma. If the final diagnosis is ganglioneuroma, no additional treatment is needed. In contrast, ganglioneuroblastomas are treated the same as neuroblastomas.

Neuroblastoma is a unique cancer in many ways. It is one of the few cancers in children that release hormones that can cause strange changes in the body, such as constant diarrhea. It can also cause changes in the some functions of the brain, such as opsoclonus (rotary movements of the eyes) and myoclonus (spastic jerks of the muscles).

These changes are called paraneoplastic syndromes.

The tumor itself can behave strangely. Sometimes the cells die without any cause and the tumor disappears. This is part of a normal process known as programmed cell death (apoptosis), the normal process that occurs when cells die. This tumor disappearance is much more common in very young infants than in older children. Another behavior that is unusual for childhood tumors is that the cells sometimes mature spontaneously to normal ganglion cells and stop dividing.

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Amplification of the MYCN gene is one of the most established genetic prognostic factors. Amplified tumours are mostly (though not exclusively) found in children aged over 1 year at diagnosis with advanced stage disease. Other genes, such as DDX1 are often co-amplified with MYCN.

Deletion of material from the chromosome 1p36 region is also associated with adverse prognosis. This is thought to be a candidate region for a suppressor gene which has yet to be identified.

Gain of 17q material is the most frequent genetic abnormality in neuroblastoma. Unbalanced 17q gain is an adverse prognostic factor and is strongly associated with adverse clinical features, 1p deletion, and MYCN amplification.

Expression of TRKA in contrast is a favourable genetic feature. This is associated with low stage and age under 1 yrear at diagnosis. TRKA is frequently supressed in MYCN amplified Tumours. Other members of the TRK neurotrophine receptor gene family, TRKB and TRKC, are also implicated in neuroblastoma.

—      Brodeur GM, et al. Biology and genetics of human neuroblastomas. [Review] J Pediatr Hematol Oncol 1997; 19(2):93-101    Related articles (PubMed)

—      Benard J Genetic alterations associated with metastatic dissemination and chemoresistance in neuroblastoma Eur J Cancer 1995; 31A(4):560-4    Related articles (PubMed)

—      Takita J, et al. Loss of heterozygosity in neuroblastomas–an overview. [Review] Eur J Cancer 1997;33(12):1971-3    Related articles (PubMed)

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