It was previously believed that prostate tumors were mutated luminal cells.  (Luminal cells line the prostate tubules.)

Immunologist Owen Witte of UCLA’s Jonsson Comprehensive Cancer Center and his colleagues have discovered that, contrary to the generally accepted hypothesis of luminal cell origin (prostate cancer cells resemble lumen cells) the mutations occur in basal cells which line the outside of the prostate tubules.   (Lumen ducts excrete prostate fluid from the prostate gland into the ejaculatory ducts.)

Owen and his team had originally developed a series of surface markers that allowed them to readily distinguish basal cells from luminal cells. They then showed that, in mice injected with human basal prostate cells, it is the basal cells that produce tumors.

These results were reported in the journal, Science.

A Ph.D student of Witte’s, Andrew Goldstein, is the lead author of the paper.

Crystals of cisplatin, a platinum compound that is used as a chemotherapy drug, are shown here
Photo – Image: National Cancer Institute

One of the first chemotherapy drugs given to patients diagnosed with cancer — especially lung, ovarian or breast cancer — is cisplatin, a platinum-containing compound that gums up tumor cells’ DNA. Cisplatin does a good job of killing those tumor cells, but it can also seriously damage the kidneys, which receive high doses of cisplatin because they filter the blood.

Now a team of scientists at the Harvard-MIT Division of Health Sciences and Technology (HST) has come up with a new way to package cisplatin into nanoparticles that are too big to enter the kidneys. The new compound could spare patients the usual side effects and allow doctors to administer higher doses of the drug, says Shiladitya Sengupta, leader of the research team.

“We could give so much more cisplatin than is now possible,” says Sengupta, an assistant professor of HST. “You could wipe out the tumor by carpet-bombing it.”

Tumors in mice treated with the new cisplatin nanoparticle shrank to half the size of those treated with traditional cisplatin, with minimal side effects. The findings were reported in the Proceedings of the National Academy of Sciences in June.

Beads on a string

Doctors began using cisplatin to treat cancer in the 1970s. Early on, doctors recognized that it harmed the kidneys, and cancer researchers began looking for alternatives. In the past few decades, the FDA has approved two less-toxic derivatives of cisplatin: carboplatin and oxaliplatin. However, those drugs don’t kill tumor cells as successfully as cisplatin.

Cisplatin’s effectiveness lies in how easily it releases its platinum molecule, freeing it to cross-link DNA strands, disrupting cell division and forcing the cell to undergo suicide. Carboplatin and oxaliplatin are less effective (but less toxic) than cisplatin because they hold on to their platinum atoms more tightly.

Sengupta and his colleagues took a new approach to making cisplatin safer: stringing cisplatin molecules together into a nanoparticle that is too large to get into the kidneys. (It has been shown that the kidneys cannot absorb particles larger than five nanometers — about 1/10,000th the diameter of a human hair).

His team designed a polymer that binds to cisplatin, arranging the molecules like beads on a string. The string then winds itself into a nanoparticle about 100 nanometers long — much too large to fit into the kidneys. However, the particles can still reach tumor cells because tumors are surrounded by “leaky” blood vessels, which have 500-nanometer pores.

Their first nanoparticle proved less effective than cisplatin, so they tweaked the polymer to make it hold a little less tightly to platinum, and ended up with a molecule with a tumor-killing power similar to cisplatin’s. However, because its side effects are minimal, the nanoparticle can be delivered in higher doses.

Daniela Dinulescu, an author of the paper and pathology instructor at Brigham and Women’s Hospital in Boston, showed that the nanoparticles outperformed cisplatin in mice engineered to develop ovarian cancer. The researchers also showed it to be effective against lung and breast tumor cells grown in the lab. Once the tumor cells die, the immune system clears platinum from the body.

The research was funded by the Department of Defense Breast Cancer Research Program and the National Institutes of Health.

It is difficult to develop and gain approval for new platinum-based compounds, says Nicholas Farrell, professor of inorganic chemistry at Virginia Commonwealth University, but he believes Sengupta’s new nanoparticles are promising. “If successful, the approach promises to maintain the status of cisplatin as one of the most useful drugs available to the clinician,” says Farrell.

The MIT researchers are now working on new variants of the nanoparticles that would be easier to manufacture. They are also making plans to test the nanoparticles in clinical trials, which Sengupta hopes will get underway within the next two years. The polymer used for the nanoparticle backbone is similar to malic acid, a natural product of cellular metabolism, so Sengupta is optimistic that it will prove safe in humans.

A new approach to processing X-ray data could lower by a factor of ten or more the amount of radiation patients receive during cone beam CT scans, report researchers from the University of California, San Diego.

Cone beam CT plays an essential role in image-guided radiation therapy (IGRT), a state-of-the-art cancer treatment. IGRT uses repeated scans during a course of radiation therapy to precisely target tumors and minimize radiation damage in surrounding tissue. Though IGRT has improved outcomes, the large cumulative radiation dose from the repeated scans has raised concerns among physicians and patients.

Reducing the total number of X-ray projections and the mAs level per projection (by tuning down the X-ray generator pulse rate, pulse duration and/or current) during a CT scan can help minimize patient’s exposure to radiation, but the change results in noisy, mathematically incomplete data that takes hours to process using the current iterative reconstruction approaches. Because CBCT is mainly used for treatment setup while patients are in the treatment position, fast reconstruction is a requirement, explains lead author Xun Jia, a UCSD postdoctoral fellow.

Based on recent advances in the field of compressed sensing, Jia and his colleagues developed an innovative CT reconstruction algorithm for graphic processing unit (GPU) platforms. The GPU processes data in parallel – increasing computational efficiency and making it possible to reconstruct a cone beam CT scan in about two minutes. (Modern GPU cards were originally designed to power 3D computer graphics, especially for video games.)

With only 20 to 40 total number of X-ray projections and 0.1 mAs per projection, the team achieved images clear enough for image-guided radiation therapy. The reconstruction time ranged from 77 to 130 seconds on an NVIDIA Tesla C1060 GPU card, depending on the number of projections – an estimated 100 times faster than similar iterative reconstruction approaches, says Jia.

Compared to the currently widely used scanning protocol of about 360 projections with 0.4 mAs per projection, Jia says the new processing method resulted in 36 to 72 times less radiation exposure for patients.

“With our technique, we can reconstruct cone beam CT images with only a few projections – 40 in most cases – and lower mAs levels,” he says. “This considerably lowered the radiation dose.”

The reconstruction algorithm is part of the UCSD group’s effort to develop a series of GPU-based low dose technologies for CT scans.

“In my mind, the most interesting and compelling possibilities of this technique are beyond cancer radiotherapy,” says Steve Jiang, senior author of the study and a UCSD associate professor of radiation oncology.

“CT dose has become a major concern of medical community. For each year’s use of today’s scanning technology, the resulting cancers could cause about 14,500 deaths.

“Our work, when extended from cancer radiotherapy to general diagnostic imaging, may provide a unique solution to solve this problem by reducing the CT dose per scan by a factor of 10 or more,” says Jiang.

Funding sources:
“This work is partially funded by the University of California Laboratory Fees Research Program. We also used GPU cards provided by NVIDIA for this project.”

The presentation:
“GPU-Based Fast Cone Beam CT Reconstruction From Undersampled and Noisy Projection Data Via Total Variation” by X Jia et al. July 21 at the Philadelphia Convention Center.

Source:
Jason Bardi
American Institute of Physics

Main News Category: Radiology / Nuclear Medicine

Also Appears In:  Cancer / Oncology,  Medical Devices / Diagnostics,

Perfusion CT scanning, an emerging imaging technology, got a bad rap last year when a machine set to incorrect radiation levels overdosed hundreds of people in Los Angeles. In the wake of this incident, researchers at the Mayo Clinic, excited by the technology’s promise for diagnosing stroke, cancer, and possibly heart disease, have developed a way to reduce the amount of radiation involved in the procedure — which, when done properly, already involves very little risk.

“At the correct dose, there should be no injury,” said Cynthia McCollough. “We believe in the clinical value of perfusion CT, so we’re trying to lower the dose and reduce the stigma.”

McCollough and her colleagues created a new image-processing algorithm that can give radiologists all of the information they need using as up to 20 times less radiation, depending on the diagnostic application. The research will be presented at the 52nd Annual Meeting of the American Association of Physicists in Medicine (AAPM) in Philadelphia.

A typical CT perfusion procedure lasts about half a minute and scans the same tissue many times, each scan at a low dose. These scans both reveal the internal anatomy of the patient and show how levels of a contrast agent, such as iodine injected into the bloodstream, change of over time. Changing concentrations of iodine can be used to calculate blood volume and flow in order to detect injuries to blood vessels or tumor responses to treatment.

The new adaptive algorithm compares these 20-30 scans and can differentiate between anatomical regions that do not change from moment to moment and those regions that carry the contrast agent –effectively reducing image noise while preserving iodine signal. The quality of each scan improves through non-linear comparisons with scans acquired earlier and later in the exam.

“When we use very low doses, the noise gets so high that it’s hard to tell what you are seeing,” said Juan Carlos Ramirez Giraldo. “With this algorithm, we’re trying to maintain both the image quality, so that a doctor can recognize the anatomic structures, and the functional information, which is conveyed by analyzing the flow of the contrast agent over the many low dose scans.”

At the AAPM meeting, the researchers will present animal data showing the effectiveness of the technique. They have also begun to process data from clinical brain perfusion CT exams in patients.

“We’re up to 15 or 20 cases that we’ve shown to the docs, and they’re all giving us the thumbs up,” said McCollough.

The presentation “20-Fold Dose Reduction Using a Gradient Adaptive Bilateral Filter: Demonstration Using in Vivo Animal Perfusion CT” by J Ramirez Giraldo et al. will be at 7:30 a.m. on Tuesday, July 20 in room 201B of the Philadelphia Convention Center.

Source: American Institute of Physics (AIP)

Main News Category: MRI / PET / Ultrasound

Also Appears In:  Radiology / Nuclear Medicine,

A team of scientists at GE Global Research, the technology development arm for the GE (NYSE: GE), has launched a study with Memorial Sloan-Kettering Cancer Center, (MSKCC) one of the world’s premier cancer centers, to better understand the early stages of colon cancer. The goal is to yield new insights that improve treatment selection and outcomes for cancer patients in the future.

“Information is one of the best weapons we have in the fight against cancer,” said John Burczak, Chief Scientist for Molecular Imaging at GE Global Research. “With colon cancer, we know that not all cases in the early stages of the disease are alike. Some are more aggressive than others. Through the promise of molecular analysis, we can identify those patients at higher risk and help ensure they receive the best possible treatment option.”

One of the primary issues in cancer diagnosis today is the limited amount of molecular information pathologists have about a particular cancer. At the time of diagnosis, little is determined about the characteristics of cancer itself such as how fast or slow it may be growing. New breakthroughs in molecular medicine are promising to change this paradigm.

Last October, GE scientists announced a major cancer research breakthrough in molecular pathology that is unlocking information about cancer previously hidden from view. This molecular information will not only increase our understanding of cancer; it could improve treatment selection for patients. This is particularly true for patients with early stage colon cancer.

Today, the standard treatment for early stage, or Stage 1 and Stage 2 colon cancer is surgery. However, the cancer recurrence rate for Stage 2 cases is high at approximately 25% because more aggressive forms of these cases go undetected.

New molecular analysis from cancer mapping tools such as GE’s have the potential to change this paradigm, so that these cases can be identified and directed to the appropriate treatment.

As part of the study, GE and MSKCC will collaborate to evaluate biomarkers for their prognostic value to segregate high from low risk early stage colon cancers. Scientists and investigators from GE and MSKCC will work together to first identify cancer cases, acquire and process cancer tissues, and collect treatment outcome information, then biochemically and statistically analyze the molecular profiles for the cancer tissues, and relate the molecular profiles to treatment outcomes.

GE’s Cancer Mapping Technology

GE scientists have developed new molecular pathology technology that can create a visual map of more than 25 proteins within a single tissue sample at the sub-cellular level and apply sophisticated imaging analysis tools to collect and interpret the data. With the ability to study multiple proteins in one sample, GE’s technology could provide more insight than ever before into the signaling networks and cell activity that may characterize different types of cancers.

Currently, a diagnosis of cancer and the decision of which therapy to prescribe are based on the histology of the tumor and, in some cases, the expression of just one or two biomarkers inside the patient’s tumor. To enable more biomarkers to be mapped and viewed together in one slide, GE researchers built a prototype system that can stain, wash and re-stain tissue samples for study under a digital microscope. The system combines image analysis of cancerous cells and structures with GE’s patented visualization tools to provide a color map of multiple protein concentrations within the sample. With the ability to visually map cancer in this way, GE is hopeful that critical information about the disease can be uncovered that was previously hidden from view.

The goal of GE’s protein mapping technology program is to provide new insights into cancer that one day will assist physicians to better determine the prognosis for a cancer and the appropriate treatment. These insights also may be useful in saving drug companies time and money in the development of new therapies. With more information, drug companies may be able to better understand what patients will and won’t respond and overall, help them make more informed choices during the development process.

GE’s research programs in protein mapping and molecular pathology are aligned with GE’s healthymagination initiative, which is built on the global commitments of reducing costs, improving quality and expanding access to healthcare for millions of people.

Source:
GE Global Research

Main News Category: Colorectal Cancer

Also Appears In:  Cancer / Oncology,

The Mattie Miracle Cancer Foundation

Peter and Victoria Brown are keeping the memory of their son, Mattie, alive by creating a foundation to help other children suffering from cancer.

Washington Post Staff Writer
Saturday, July 24, 2010

Peter and Victoria Brown stood across from the Capitol building getting ready, looking over the list of members of Congress they planned to visit that day.

When 6-year-old Darya Egorova was first diagnosed with bone cancer – doctors told her parents there was a good chance they would have to amputate her leg. But thanks to a revolutionary new procedure — that took less than three hours — the Russian girl is cancer free, the Daily Mail reported.

Darya was diagnosed by Russian doctors who told her parents they had very few treatment options that would allow her to stay mobile. Her parents were devastated, but a Russian cancer charity, Grant Life, changed all that, when they volunteered to help pay for a new procedure in Britain.

Darya and her parents traveled to the Harley Street Clinic in London where doctors removed 4 inches of cancer-ridden bone from her right shin including a 2-inch tumor. The bone was then blasted with very high doses of radiotherapy and reinserted back into her leg.

Two days after the pioneering surgery, Darya attempted to walk with crutches, and left hospital within a week. Now, one year later, she’s standing tall, dancing, playing sports and enjoying school.

Doctors said over the next two years, the healthy bone will grow through the dead bone, and bring it back to life.

“Given the surgical options my daughter was offered outside the U.K., what surgeons have done is truly a miracle,” Darya’s mom, Irina, told the newspaper.

HealthFirst reporter Leslie Toldo tells us about this new treatment for the most common childhood bone cancer.

Osteosarcoma usually strikes in the leg, just above the knee. In the most challenging cases, amputation is the only option.

This new implant may change that.

Step by step, Haley Richardson is beating cancer. Last year, an MRI revealed a tumor in her right femur. To eliminate the cancer, doctors had to remove bone in Haley’s thigh.

Her leg was saved thanks to this implant. It connects her remaining femur to her lower leg with a hinge joint to replace her knee. As Haley grows, this unique prosthesis can be extended to grow with her.

“Traditional implants for growing kids didn’t work, and they didn’t work well because the child is growing and the implant doesn’t grow,” explained Dr. Mary I. O’Connor, an orthopedic surgeon at the Mayor Clinic in Jacksonville, Fla. “We put a little coil around Haley’s leg and we can turn that on, and that emits a signal that’s picked up by a receptor in her implant that expands the coil so the implant actually lengthens.”

“At first, I was a little scared of it. But now I’m starting to get used to it,” Haley said. “Now I’m starting to walk on it a little more than I did.”

Haley’s still getting the hang of her new knee and finishing up her chemo.

Life is now full of possibilities.

“She’s going to be able to ride a bike. She’s going to be able to swim. She’s going to be able to dance at her prom. You know, important things like that,” O’Connor said.

A brave little girl who is painting a picture of a big, bright future without cancer.

This device is perfect for young bone cancer patients who still have growing to do.

It is expensive, however, costing about $30,000.

When Haley is all grown up, doctors may give her a permanent, fixed implant.

BACKGROUND: Osteosarcoma is a type of cancer that starts in the bones. Every year, about 400 children in the United States are diagnosed with the cancer. It is the most common type of cancer that develops in bone. Most osteosarcomas occur in children and young adults. Teens are the most affected age group; however, this type of cancer can occur at any age. Osteosarcoma usually develops in areas where the bone is growing quickly, such as near the ends of the long bones. Most tumors develop in the bones around the knee, either in the distal femur (the lower part of the thigh bone) or the proximal tibia (the upper part of the large lower leg bone).

TREATMENT: The most common treatment for osteosarcoma is surgery, and sometimes, amputation. In addition, chemotherapy is also typically required. According to the University of Texas Cancer Center, treatment usually begins with chemotherapy, then surgery, then post-surgery treatment (chemotherapy, radiation and sometimes hormone or biological therapy). These post-surgery treatments ensure the remaining cancer cells have been completely destroyed. In the past, before technological advances and medical breakthroughs, amputation was the only option. Nowadays, doctors aim to save the child’s leg and safely remove the tumor without amputating the leg.

NEW TECHNOLOGY: “Today, there is a newer alternative: a femoral prostheses that grows with the patient,” Mary I. O’Connor, M.D., an orthopedic surgeon from the Mayo Clinic in Jacksonville, Fla., told Ivanhoe. “The device can be adjusted for patient growth by heating the plastic structure of the implant, which uncoils an internal spring and stretches the patient’s leg to the appropriate length.”

A benefit of this newer replacement is that multiple operations are not necessary as the child grows and develops. The prosthesis can be adjusted just a few millimeters at a time. This feature makes the implant especially attractive for younger patients who still have some growing to do. Unfortunately, many insurance companies do not cover the prosthesis, and the cost is around $30,000.

FOR MORE INFORMATION:
Cynthia R. Nelson, Public Affairs
Mayo Clinic Florida
Jacksonville, FL
904-953-0464
nelson.cynthia1@mayo.edu

Francesco Loccisano Way Dedicated In Dyker Heights

DYKER HEIGHTS — Francesco Anthony Loccisano (aka Frankie) was a charming and vibrant 17-year-old boy who was dearly loved and adored by his large family and many friends, most of whom had attended his street naming ceremony this past Saturday on 63rd Street and 14th Avenue.

Thanks to Community Board 11 and Councilmembers Sara Gonzalez and Vincent Gentile, among others, Rocco and Camille Loccisano’s dream had become a reality.

Frankie was filled with positive energy and enthusiasm. His loving family watched as he grew into an intelligent teenager. During his too-short life, he brought nothing but joy and happiness into the lives of all those around him. Frankie was dependable, responsible, a bright student and a great friend. His favorite subject was history, and he loved politics and economics. He also enjoyed a good and fair debate and he always presented facts to support his views.

His dream was to one day study law and practice as a criminal prosecutor. He even had thoughts of becoming a member of Congress. Congressman Michael McMahon, who spoke at the street-naming event, said, “Frankie was an inspiration to us all. This monument to his name will enable people who pass this way to look up and know Francesco Loccisano was someone special.”

His political views were moderate, and he always said, “depends on the issue!” He enjoyed football, was a Yankee fan, loved gangster movies, video games, online role playing and neighborhood stoopball. He appreciated simple pleasures, but he also enjoyed the finer things in life, such as handsome neckties and fine restaurants. He was a talented, creative writer and also an avid novel reader.

Frankie’s journey with childhood cancer began at the age of 14 during his freshman year of high school. He was diagnosed with Osteosarcoma and later on a second cancer, Leukemia. He fought a long and hard battle against such illness for 27 months.

Many rounds of chemotherapy, radiation, multiple lung surgeries and an above the knee amputation are among the countless and various types of treatments that Frankie bravely endured in an effort to save his life. Along this journey, Frankie learned many life lessons, most especially about the hardships of humanity. This caused him to grow a tremendous compassion for those who were less fortunate, ill, or in pain. He vowed to start his own foundation because he wanted to help other children and families who were experiencing illness and misfortune.

As an older pediatric patient, Frankie especially understood the enormity of childhood cancer and what it meant to be so young and fighting for life instead of enjoying life. He prayed for anyone he was told about, young or old, no matter what their misfortune.

Through his own difficult time, he remained hopeful as well as prayerful. He kept Jesus as the center of his life and prayed to his special Catholic Saints, Padre Pio and St. Joseph. His desire to help other children were the last words he communicated to his family. On the day he passed, he was surrounded by those who loved him.

Frankie’s journey continues with the “Francesco Loccisano Memorial Foundation”, a grass-roots organization founded by Frankie’s family and friends who have pledged to remember the daily battle of children with cancer. His remarkable life and his sincere and heartfelt desire to help others are the pillars, the heart and the cornerstone of this foundation.