Friday, April 13, 2012

Wilm's Tumor In Children

Wilm's tumor is a rare type of cancer that is found mainly in children. Another name for Wilm's tumor is nephroblastoma and it is the most common cancer of the kidneys.  The age range of a child is 3-4 years old is when the Wilms tumor usually develops.  This specific tumor is usually seen on just one of the kidneys, but can be seen in both.

                                                     Wilms Tumor in kidneys of a child

Approximately 500 cases are seen every year in the United States. Fortunately, this type of tumor is highly responsive to treatment.

Wilms' tumor is a malignant tumor containing metanephric blastema, stromal and epithelial derivatives. Characteristic is the presence of abortive tubules and glomeruli surrounded by a spindled cell stroma. The stroma may include striated muscle, cartilage, bone, fat tissue, fibrous tissue. The tumor is compressing the normal kidney parenchyma.
The mesenchymal component may include cells showing rhabdomyoid differentiation. The rhabdomyoid component may itself show features of malignancy (rhabdomyosarcomatous Wilms).
Wilms' tumors may be separated into 2 prognostic groups based on pathologic characteristics:
  • Favorable - Contains well developed components mentioned above
  • Anaplastic - Contains diffuse anaplasia (poorly developed cells)

The symptoms that are typical of Wilm's tumor are an abnormally large abdomen, abdominal pain,fever,nausea and vomiting,blood in the urine and high blood pressure in some cases.

The diagnosis of this tumor requires several tests.

  • A physical examination. The doctor will look for possible signs of Wilms' tumor.
  • Blood and urine tests. Blood tests can't detect Wilms' tumor, but they can provide your child's doctor with an overall assessment of your child's health.
  • Imaging tests. Imaging tests that create pictures of your child's kidneys can help your doctor determine whether your child has a kidney tumor. Imaging tests may include ultrasound, computerized tomography (CT) and magnetic resonance imaging (MRI).
  • Surgery. If your child has a kidney tumor, your doctor may recommend removing the tumor or the entire kidney to determine if the tumor is cancerous. The removed tissue is analyzed in a laboratory to determine whether cancer is present and what types of cells are involved. This surgery may also serve as treatment for Wilms' tumor.
Once your child's doctor has diagnosed Wilms' tumor, he or she works to determine the extent (stage) of the cancer. Your child's doctor may recommend a chest X-ray, chest CT scan, chest MRI and bone scan to determine whether the cancer has spread beyond the kidneys. 

The growth of the cancer is usually described in Stages.  The following are the stages for Wilm's tumor.

  • Stage I. The cancer is found only in one kidney, and generally can be completely removed with surgery.
  • Stage II. The cancer has spread to the tissues and structures near the affected kidney, such as fat or blood vessels, but it can still be completely removed by surgery.
  • Stage III. The cancer has spread beyond the kidney area to nearby lymph nodes or other structures within the abdomen, and it may not be completely removed by surgery.
  • Stage IV. The cancer has spread to distant structures, such as the lungs, liver, bones or brain.
  • Stage V. Cancer cells are found in both kidneys.
·         Standard treatment for Wilms' tumor is surgery and chemotherapy. The stage of the tumor and appearance of the cancer cells under a microscope help determine whether your child also needs radiation therapy. At this point, your doctor may tell you the tumor appears to be either favorable or unfavorable (anaplastic) — the histology of the tissue. Children whose tumors have a favorable histology have better survival rates. However, many children with unfavorable histology also have good outcomes.
·         Because this type of cancer is rare, your doctor may recommend that you seek treatment at a children's cancer center that has experience treating this type of cancer.

Professor Frank Friedman explains Wilm's Tumor Kidney Cancer in Children

More information :, 


Wednesday, April 11, 2012

Dedicated Reseachers Are Committed to Tackling Liver Cancer

There are researchers that have dedicated their careers to finding cures for certain cancers. The following news story is one of hope for those persons who have liver cancer.

Ulla Hansen is a scientist who fell in love with a protein. She began studying it nearly three decades ago as a postdoctoral fellow at MIT because of its potential to solve the mystery of how cells grow. She continued those studies as a faculty member at the Dana-Farber Cancer Institute and Harvard Medical School. And now the College of Arts & Sciences biology professor has discovered that this same protein, transcription factor LSF, also referred to as late SV40 factor, appears to play a role in the growth of liver cancers. Understanding that role could be the key to a treatment for the deadly disease.

It’s incredibly gratifying personally that all of our basic science all these years has come to a position now where we may be able to translate it into the clinics,” says Hansen, director of BU’s program in molecular biology, cell biology, and biochemistry.

Liver cancer may not garner the media attention that other cancers do, but it is the fifth most common cancer and the world’s third leading cause of death from cancer. And while the rate of diagnosis for other cancers in the United States is declining, diagnosis of liver cancer is rising, largely because of its connection to an increasing incidence of hepatitis C.

“We’re still trying to figure out all the genes that LSF targets and turns on and off,” she says. “Most transcription factors target at least hundreds of genes, if not thousands.”
For many years, Hansen’s laboratory was the only one in the world to focus on LSF’s role in cell growth and division. It wasn’t unusual for her to get phone calls from scientists around the world wanting to share their own LSF-related discovery.
Devanand Sarkar was one. He called from the Virginia Commonwealth University Institute of Molecular Medicine to tell Hansen that he had found higher levels of LSF in cells after his lab turned on a gene that causes metastasis. “Usually there’s a few thousand LSF entities per cell, but this went up tenfold or twenty-fold,” Hansen says. And when Sarkar looked specifically at liver cancer cells, he saw that the more advanced the cancer had become, the more LSF was present. The two concluded that LSF not only encourages normal cell growth, but also liver cancer cell growth.

What she really needed, she decided, were some small-molecule inhibitors, or chemical torpedoes, that specifically targeted LSF and disabled it. She found a source in a Nevada company, Sierra Sciences. Researchers there have spent years working on a way to prevent aging (the company motto: Cure Aging or Die Trying) and had toyed with the idea that controlling LSF was key. They had screened 110,000 small-molecule inhibitors and found 80 strong candidates, none of which worked. So they put their work on ice, literally.
When Hansen got in touch with the company about a possible collaboration, the chief scientific officer offered to just send her everything they had.
“I couldn’t believe it,” Hansen says. “This is not the way companies usually act. But they’re not interested in money. They were happy to help.”
After plugging the compounds into liver cancer cells to see if they turned off LSF, Hansen and her team found several encouraging candidates. But they needed more of each compound. Sierra Sciences had included the chemical structures for each compound, but she had no idea how to buy more.
“I decided the best option in this nice interdisciplinary building,” Hansen says, referring to BU’s Life Sciences and Engineering Building, “was to go upstairs to ask some nice synthetic organic chemists how they would go about ordering more of these things.”

So she walked up to the chemistry department and started knocking on doors. Scott Schaus’ was the first to open. The two chatted about her research briefly as Schaus typed away on his computer. Then, Hansen recalls, he looked up and asked, “Do you want us to synthesize it for you?”
She accepted the offer immediately.
Schaus, a CAS associate professor of chemistry and bioinformatics, recruited two graduate students to work on the project. One synthesized compounds, the other tested them to see which were most effective at knocking down LSF. Those compounds were then passed along to Hansen’s team, which tested them in liver cancer cells. Together the labs have identified at least three highly effective small-molecule inhibitors, with FQI2 (dubbed “Ficky 2” by the graduate students) the most promising.
Hansen has since tested the compounds in mice with liver cancer cells and seen impressive results. “Our small-molecule inhibitors are in fact knocking LSF down to nothing,” she says. But that’s not the only good news. “We see absolutely no side effects in the mice.”
It now seems that liver cancer cells need LSF to grow, divide, and multiply. Normal cells do not, or at least have found other ways to work around the protein. Hansen is now trying to figure out why.

Tuesday, April 10, 2012

Colorectal Cancer Patients Drug Resistance

Recent research has discovered in the lab a way to overcome drug resistance in colorectal cancer.  This recent article explains the the findings and it is great news!

The results, which highlight the use of a novel drug called ARI-4175, may eventually point to new approaches that can be used in treating other cancers
When combined with other treatments, the drug cetuximab—which works by slowing or stopping the growth of cancer cells—has been shown to extend survival in certain types of cancer, including metastatic colorectal cancers. Unfortunately, about 40 percent of colorectal cancer patients—specifically those who carry a mutated form of a gene called KRAS—do not respond to the drug. Researchers at Fox Chase Cancer Center in Philadelphia, however, have been working on a way to overcome this resistance to cetuximab by unleashing a second cetuximab driven mechanism using a novel drug called ARI-4175.
In mice that had KRAS mutated colorectal cancer, researchers found that ARI-4175 not only blocked tumor growth when used alone, but also when used in combination with cetuximab. They hypothesize that the new drug may work by enlisting "natural killer" cells of the body's own immune system to reject the tumor.
"We've discovered that ARI-4175 appears to increase the level of natural killer cells that could play a role in rejecting the tumor," Hossein Borghaei, DO, director of thoracic medical oncology at Fox Chase and lead author on the study says. He notes that this action—rallying the body's own immunologic defenses—may explain why ARI-4175 effectively stops the growth of tumors. "My theory is that this particular drug turns on the host's anticancer immune response, while cetuximab serves to help direct it toward the cancer."
Borghaei, along William W. Bachovchin, PhD, professor of biochemistry at Tufts Sackler School of Graduate Biomedical Sciences (also co-author on the study) and colleagues, tested ARI-4175 in colorectal cancer cell lines and in mice with two types of cetuximab-resistant colorectal tumors.
Neither cetuximab nor ARI-4175, separately or together, succeeded in killing the cells in lab dishes. In the mice, however, ARI-4175 blocked tumor growth, and was more successful at higher doses of the drug. The research shows an even stronger effect in mice that received ARI-4175 combined with cetuximab.
Cetuximab, which is FDA-approved for metastatic colorectal cancer and some head and neck cancers, works by blocking a crucial receptor on the surface of a cancer cell—causing the cell to die. In people carrying the mutated form of the KRAS gene, cetuximab is not effective, but ARI-4175 may open up a detour around that impasse.
Borghaei notes that a cancer treatment like the immune stimulator ARI-4175, which uses the body's own defenses, may be more effective than drugs targeting tumor oncogenes that are susceptible to mutations that lead to resistance. "Tumors often develop resistance to targeted therapies," he says, "but it's more difficult to find resistance to a patient's own immune system. Bringing in the activity of the immune system might be the most effective way to fight some of these cancers."
"Our immune system can actually be a very useful partner in the fight against cancer," he says.
The researchers say their results suggest ARI-4175 warrants further testing in clinical trials. Although the researchers investigated colorectal cancer, their findings may also point to new approaches to treating other types of cancer. "If we can show that the drug overcomes resistance to cetuximab, it can be used against head and neck cancers as well," says Borghaei.

Monday, April 9, 2012

Gastronintestinal Stromal Tumor (GIST)

A medical definition of a tumor is when normal cells change and grow uncontrollably. A tumor can be benign (noncancerous) or malignant (cancerous, meaning it can spread to other parts of the body).

A gastrointestinal stromal tumor (GIST) is a type of tumor that occurs in the gastrointestinal (GI or digestive) tract, including the esophagus, stomach, gallbladder, liver, small intestine, colon, rectum, and lining of the gut. GISTs are different from other, more common types of gastrointestinal tumors because of the type of tissue in which they start. Originally, GISTs were thought to be either muscle or nerve tumors, but recent research shows that GISTs start in cells found in the walls of the GI tract, called interstitial cells of Cajal (ICC). These cells send signals to the GI tract to help move food and liquid through the system.
GISTs belong to a group of cancers called soft tissue sarcoma. Soft tissue sarcomas are a group of cancers that develop in the tissues that support and connect the body, and the sarcoma cells resemble the cells that hold the body together, including fat cells, muscles, nerves, tendons, joints, blood vessels, or lymph vessels.
It is important to note that all GISTs can become malignant. Sometimes it may be hard for the doctor to tell immediately whether a GIST is likely to come back after treatment. As a result, the doctor will look at many factors to determine the best treatment, including the size of the tumor, whether it has already spread, how many dividing cells there are, and the tumor’s location.

Gastrointestinal stromal tumors are a group of mesenchymal neoplasms that arise from precursors of the connective-tissue cells of the gastrointestinal tract. They occur predominantly in middle-aged and older persons, and approximately 70 percent of the tumors are found in the stomach, 20 to 30 percent are found in the small intestine, and less than 10 percent are found elsewhere in the gastrointestinal tract. Recent studies have shown that cells in gastrointestinal stromal tumors express a growth factor receptor with tyrosine kinase activity termed c-kit. This receptor, the product of the proto-oncogene c-kit, can be detected by immunohistochemical staining for CD117, which appears to be the most specific diagnostic criterion for the diagnosis of gastrointestinal stromal tumors. The ligand for the c-kit receptor is stem-cell factor, also known as steel factor or c-kit ligand. Mutations of c-kit that cause constitutive activation of the tyrosine kinase function of c-kit are detectable in most gastrointestinal stromal tumors and appear to play a central part in the pathogenesis of these tumors. These mutations result in ligand-independent tyrosine kinase activity, autophosphorylation of c-kit, uncontrolled cell proliferation, and stimulation of downstream signaling pathways, including those involving phosphatidylinositol 3-kinase and mitogen-activated protein kinases. Gastrointestinal stromal tumors are notoriously unresponsive to cancer chemotherapy, and there is no effective therapy for advanced, metastatic disease.

The drug for treatment is Gleevec (which is also an oral chemo treatment for myelogenous leukemi).  Another treatment that is new is Sutent.