Archive for the ‘General Cancer Research’ Category

Researcher identify the prostate cell that mutates into cancer

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Posted 29 Jul 2010 — by James Street
Category General Cancer Research, Prostate Cancer, genetic research

On July 29, 2010 UCLA researchers announced that they have identified the prostate cell that mutates into prostate cancer.

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.

Super-sizing a cancer drug minimizes side effects

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Posted 28 Jul 2010 — by James Street
Category Chemotherapy, NanoTechnology

Crystals of cisplatin, a platinum compound that is used as a chemotherapy drug, are shown here
Photo – Image: National Cancer Institute
Researchers design a new version of cisplatin that spares the kidneys, letting doctors use higher doses.
Anne Trafton, MIT News Office

July 28, 2010

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.

Video Game Processors Help Lower CT Scan Radiation

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Posted 28 Jul 2010 — by James Street
Category Diagnostic, Imaging

22 Jul 2010

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

Article URL: http://www.medicalnewstoday.com/articles/195554.php

Main News Category: Radiology / Nuclear Medicine

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

Image-Processing Algorithm Reduces CT Radiation Dose By As Much As 95 Percent

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Posted 28 Jul 2010 — by James Street
Category Diagnostic, Imaging, Uncategorized

21 Jul 2010

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)

Article URL: http://www.medicalnewstoday.com/articles/195346.php

Main News Category: MRI / PET / Ultrasound

Also Appears In:  Radiology / Nuclear Medicine,

GE Launches Study To Improve Diagnosis Of Early Stage Colon Cancer

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Posted 28 Jul 2010 — by James Street
Category Colon Cancer, Individualized treatment, Molecular

23 Jul 2010

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

Article URL: http://www.medicalnewstoday.com/articles/195579.php

Main News Category: Colorectal Cancer

Also Appears In:  Cancer / Oncology,

When should a scientist’s data be liberated for all to see?

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Posted 23 Jul 2010 — by James Street
Category Finance and Politics of osteosarcoma research

From Scientific American Magazine

Jul 22, 2010 02:01 PM in Basic Science | 8 comments

By Katherine Harmon

scientists collecting research data, but debate if should be released immediately into commonsWhen researchers make an exciting discovery, the data behind it are often closely guarded until they can be examined, developed and then revealed—at least in part—in a peer-reviewed journal with all of the proverbial fanfare.

But that custom often leaves the public and most of the research world in the dark—sometimes for years, as some lamented in the case of the formal description of the hominid Ardipithecus ramidus, which came some 15 years after the original discovery. Publication usually involves sharing some data because the scientific method encourages others to review one’s work so they can attempt to replicate it. But in a web-driven era of rapidly moving and easily stored data, however, many researchers now argue forcefully for an open exchange of data and the wider use of so-called scientific commons.

Climate change, molecular chemistry and microbiology are just a few of the fields currently entertaining the idea of a better-connected repository to which data can (or must) be uploaded soon after discovery. And in the medical world, many researchers are looking hopefully toward a digital future in which masses of patient data can be examined for patterns of disease soon after they are gathered.

“It would be preferable, from a pure scientific advancement standpoint, to have every piece of data released immediately to the public,” Jorge Contreras, deputy director of the Intellectual Property Program at Washington University’s School of Law in St. Louis, Mo. and author of a new policy essay on the topic published online July 22 in Science, said in a prepared statement.

That idealistic approach, however, “doesn’t give data-generating scientists the opportunity to publish and advance their careers through publication,” he noted. Thus new findings and data sets are still usually held close to the vest in the harsh publish-or-perish world.

And the data dearth doesn’t necessarily stop with publication. “Because of busy schedules, competitive pressures and other interpersonal vagaries, the sharing of scientific data can be inconsistent even after publication,” Contreras observes in his essay.

Not every field has been so tight-fisted with its data. As an encouraging example, he points to the Human Genome Project’s stipulation that all new data be made public within 24 hours of being generated. But, he concedes, not every discipline is primed to fall in line with such immediate free access. The genome “represented the common heritage of the human species and should not be encumbered by patents,” he writes. But patents are precisely the point of many scientific endeavors, and showing your cards to the competition early on is a patently dim decision.

Thus Contreras proposes a balance of data access and data rights. “I think you must have a compromise,” he said in a prepared statement. “Commons weighted too heavily in favor of data users are not likely to attract sufficient contributions from data generators, whereas commons weighted too heavily in favor of data generators” would be less helpful to other scientists and the public.

But that doesn’t mean data should be held back. Instead, he argues, widely accepted lead times—after data are publicly released but before others can publish results on them—would allow “data generators a ‘head start’ on preparing publications based on their data, yet data are still broadly available for the general advancement of science.”

Image courtesy of iStockphoto/AlexRaths

Francesco Loccisano Memorial Foundation

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Posted 19 Jul 2010 — by James Street
Category Finance and Politics of osteosarcoma research, Foundations

Heroic Brooklyn Youth Gets Street Named in His Memory
by Brooklyn Eagle (edit@brooklyneagle.net), published online 07-19-2010

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.

Mistletoe and solid tumors

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Posted 19 Jul 2010 — by James Street
Category General Cancer Research

One of the most obvious differences in the practice of oncology in the United States and in Europe is the differing attitude towards mistletoe (Viscum album). European oncologists have used extracts of mistletoe for the past 90 years and such usage is no longer controversial there. By some estimates, 40 percent of French (Simon 2007) and up to 60 percent of German cancer patients receive this botanical extract (Schönekaes 2003). On the other hand, the use of Iscador and other mistletoe extracts is virtually unknown in the United States. Both Europe and the US have well trained and highly competent oncology communities, yet they differ profoundly on this, as well as a number of other issues concerning cancer treatment. This difference is a vivid illustration of the effects of cultural norms on medical practice (Payer 1998).
Iscador is an extract of the white berries of the mistletoe plant, an unusual evergreen plant that grows as a kind of parasite in trees across Europe. Globular mistletoe is a familiar sight in Germany, especially in the winter when it stands out in the bare branches of various deciduous trees. Mistletoe has a fascinating history. According to Roman authors, mistletoe was used medicinally by Celtic priests, who gathered it using golden scythes (to avoid contaminating the specimens). Much later, Rudolf Steiner (1861-1925), the founder of Anthroposophical Medicine, introduced as a cancer treatment (Steiner 1985).
The key question is whether mistletoe has anticancer effects or not. If it does not, then European doctors should stop using it (or recognize it as a placebo). If it does work, then American oncologists should adopt it as a useful adjunctive therapy. (No one I know regards it as a cure).
Earlier this year, I discussed several positive studies with mistletoe. Since then, several additional studies have added weight to the pro-mistletoe argument. Jessica Burkhart, Stephan Baumgartner, et al. of the University of Bern, Switzerland, investigated the effects of mistletoe on the adverse effects of the drug cyclophosphamide (Cytoxan) in cell line studies. The article appeared in Alternative Therapies in Health and Medicine in May-June 2010. The experiment involved normal white blood cells (peripheral blood mononuclear cells, or PBMCs) as well as a T-cell leukemia Jurkat cell line. Cells were first pre-incubated with mistletoe extract. Then a form of cyclophosphamide was added. After that, mitochondrial activity and replication were both measured.
The results were that mistletoe extract “strongly stimulated” healthy PBMCs but not malignant Jurkat cells. The level of activity of these cells was doubled by the addition of mistletoe (197 percent with the lower dose and 225 percent with the higher dose). In addition, mistletoe partially protected healthy PBMCs, but not malignant cells, from the damage inflicted by cyclophosphamide.
This is further scientific confirmation of the purported uses of mistletoe to reduce the adverse (side) effects of a widely used form of conventional chemotherapy. Mistletoe exerts immune modulating as well as direct anti-proliferative effects. Mistletoe may also increase levels of various anti-cancer cytokines including tumor necrosis factor (TNF-alpha).

This year, at the American Society for Clinical Oncology (ASCO) meeting, Washington DC scientists presented the results of a phase I clinical trial on the use of European mistletoe extracts and the drug gemcitabine (Gemzar) in patients with advanced solid tumors (Mansky 2010).  Gemcitabine and osteosarcoma The product tested was Helixor (not the more common Iscador). These researchers’ conclusions were highly positive. They reported that the combination had limited toxicity, no alteration in gemcitabine uptake, good tolerability and a clinical benefit in 48 percent of patients. (This contrasts well with previously reported levels of benefit from gemcitabine alone.)
They concluded that the addition of European mistletoe extracts “may allow for use of higher doses” of gemcitabine and that the combination of mistletoe and this drug “warrant further study.”
Studies of this sort continue to chip away at the standard American oncologists’ contention that all useful treatments are routinely employed in US oncology hospitals and that any other ways of treating the disease are without scientific validity. This is simply not true. In fact, American oncologists could learn a great deal from CAM practitioners, if they would recognize that other cultures have different ways of approaching the same problems, and that have something valuable to contribute to the optimal treatment of cancer patients.

Burkhart J, Wälchli C, Heusser P, et al. In vitro investigation into the potential of a mistletoe extract to alleviate adverse effects of cyclophosphamide. Altern Ther Health Med. 2010;16(3):40-48.
Mansky P, et al. NCCAM/NCI phase I study of mistletoe extract and gemcitabine in patients with advanced solid tumors. Abstract No: 2559; J Clin Oncol. 2010;28:15s (suppl; abstr 2559)
Payer, Lynn. Medicine and Culture, revised edition. New York: Holt, 1996.
Schönekaes K, Micke O, Mücke R, et al. [Use of complementary/alternative therapy methods by patients with breast cancer]. Forsch Komplementarmed Klass Naturheilkd. 2003;10(6):304-308.


Simon L, Prebay D, Beretz A, et al. [Complementary and alternative medicines taken by cancer patients]. Bull Cancer. 2007;94(5):483-488.
Ziegler R, Grossarth-Maticek R. Individual Patient Data Meta-analysis of Survival and Psychosomatic Self-regulation from Published Prospective Controlled Cohort Studies for Long-term Therapy of Breast Cancer Patients with a Mistletoe Preparation (Iscador). Evid Based Complement Alternat Med. 2008. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/18955332 [Accessed July 9, 2010].

Hypoxia and hypoglycaemia in Ewing’s sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor)

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Posted 16 Jul 2010 — by James Street
Category Molecular Osteosarcoma Studies, genetic research

Little is known regarding HIF expression and function in primary bone sarcomas.

We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing’s sarcoma and osteosarcoma. Methods: HIF-1 alpha and HIF-2 alpha immunohistochemistry was performed on a Ewing’s tumour tissue array.

Ewing’s sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA.

Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration.

Results:

17/56 Ewing’s tumours were HIF-1 alpha-positive, 15 HIF-2 alpha-positive and 10 positive for HIF-1 alpha and HIF-2 alpha.

Expression of HIF-1 alpha and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1 alpha and HIF-2 alpha in Ewing’s and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2 alpha in Ewing’s.

Downstream transcription was HIF-1 alpha-dependent in Ewing’s sarcoma, but regulated by both isoforms in osteosarcoma.

In both cell types hypoglycaemia reduced cellular proliferation by over 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration.

Conclusions:

Co-localisation of HIF-1 alpha and necrosis in Ewing’s sarcoma suggests a role for hypoxia and / or hypoglycaemia in in vivo induction of HIF.

In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing’s and osteosarcoma, driving effects on proliferation and apoptosis.

These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

Author: Helen KnowlesKarl-Ludwig SchaeferUta DirksenNicholas Athanasou

Credits/Source: BMC Cancer 2010, 10:372

Distant Sarcomas Shrunk By Genetically Reprogrammed HSV

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Posted 13 Jul 2010 — by James Street
Category Vaccine Studies

08 Jul 2010

Scientists have used a genetically reprogrammed herpes virus and an anti-vascular drug to shrink spreading distant sarcomas designed to model metastatic disease in mice – still an elusive goal when treating humans with cancer, according to a study in the July 8 Gene Therapy.

Less than 30 percent of patients with metastatic cancer survive beyond five years, despite the aggressive use of modern combination therapies, including chemotherapy. This creates a significant need for new sarcoma therapies to treat metastatic disease, said Timothy Cripe, M.D., Ph.D., a physician/researcher in the division of Hematology/Oncology at Cincinnati Children’s Hospital Medical Center and the study’s senior investigator.

The study results are even more significant because the oncolytic herpes virus, HSV-rRp450, was given to the mice systemically to attack tumors via the blood stream instead of being injected directly into tumors.

“Systemic bio-distribution has been a major stumbling block for using virus vectors in gene transfer and virotherapy to treat cancer, but we show that viruses can be used systemically by giving them intravenously to get an anti-tumor effect,” Dr. Cripe said.

Also important to results of the current study was using the virus in conjunction with a drug (bevacizumab) that blocks the growth of tumor feeding-blood vessels. In the current study, researchers focused on spreading Ewing sarcoma and Rhabdomyosarcoma – cancers that form in muscle, bone and connective tissue.

Anti-angiogenic agents like bevacizumab are usually given first in combination cancer therapies because they help enlarge intercellular openings to tumor cells and ease the delivery of drugs, such as chemotherapies. In this study, however, the researchers discovered that bevacizumab has to be given after the virus to maximize the anti-tumor effect of the combined therapy. In fact, giving bevacizumab first lowered the virus’s uptake in cancer cells.

The rRp450 oncolytic virus used in the study was derived from herpes simplex type 1. The virus was genetically modified by scientists by removing a gene that makes the virus unable to replicate efficiently in dormant cells. This causes the virus to selectively target and replicate in rapidly growing cancer cells while leaving normally dormant healthy tissue cells alone.

After removing the one gene from the virus, researchers replaced it with a gene that encodes an enzyme that activates a class of anti-tumor chemotherapies called oxazaphosphorines. The overall therapeutic approach is for the virus to infect and degrade the cancer cells and then activate chemotherapy agents as anti-angiogenic agents cut off vascular growth and blood supply to the tumors.

In the current study, however, researchers treated the mice only with rRp450 and the anti-angiogenic drug bevacizumab. This allowed them to test whether the virus could be given systemically, how anti-angiogenic drugs affected virus tumor uptake and the impact this had on tumor growth.

In mice receiving bevacizumab prior to the rRp450, overall tumor shrinkage averaged 40 percent. In mice receiving rRp450 before bevacizumab, tumor size was reduced by an average of 75 percent. The researchers also reported that mice treated with rRp450 before bevacizumab had longer survival rates.

Results of the current study could be used immediately to help design subsequent research into treatment protocols for oncolytic viruses, particularly clinical trials involving combination therapeutic strategies, Dr. Cripe said. Clinical trials are underway in the United States and Europe using oncolytic herpes viruses similar to the one used in the current study.

Other researchers involved in the current study include the first author, Francis Eshun, M.D., and Mark Currier, Rebecca Gillespie, Jillian Fitzpatrick and William Baird, all of the Division of Hematology/Oncology at Cincinnati Children’s and its Cancer and Blood Diseases Institute. Funding support for the study from the Cincinnati Children’s Division of Hematology/Oncology, teeoffagainstcancer.org, the Katie Linz Foundation, the Limb Preservation Foundation, the American Cancer Society and the National Institutes of Health.

Source:
Nick Miller
Cincinnati Children’s Hospital Medical Center

Article URL: http://www.medicalnewstoday.com/articles/194121.php

Main News Category: Cancer / Oncology

Also Appears In:  Genetics,  Infectious Diseases / Bacteria / Viruses,  Vascular,

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