Archive for the ‘Human osteosarcoma research’ Category

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,

Genome Studies Start to Unravel Prostate Cancer’s Complexity

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Posted 29 Jun 2010 — by James Street
Category Prostate Cancer, genetic research, genetic research

Genome Studies Start to Unravel Prostate Cancer’s Complexity

Illustration of a DNA strand

Researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) have completed the largest genomic analysis of prostate tumors to date. The results, based on clinical and genomic information collected from 218 patients, provide an overview of the common genetic changes in the disease and point to new directions for research, including a way to potentially differentiate aggressive tumors from those that are not life threatening. The researchers have made the data available to the community through a public Web site, and a summary of the results appeared online last week in Cancer Cell.

“We now have a much better picture of the common genetic alterations in prostate cancer,” said lead investigator Dr. Charles Sawyers. Although more samples need to be analyzed, he continued, the results could provide a roadmap for designing future clinical trials in this disease. “When it comes to developing and testing targeted cancer drugs, you need to be able to subclassify patients, and you can’t do this intelligently until you know what the alterations are.”

This would change how doctors talk to patients about the disease and the need for adjuvant therapy or not, which is why this finding is so exciting.

—Dr. Jonathan Simons

Genome studies have yielded insights into glioblastoma and cancers of the lung, colon, pancreas, and breast, but prostate cancer has been a challenge. Prostate tumors are relatively small, and expert pathologists are needed to obtain adequate samples of tumor tissue. With a large prostate cancer program and skilled pathologists, MSKCC was able to overcome these challenges.

“Dr. Sawyers and his colleagues have made an extraordinarily important contribution to the field of prostate cancer research,” said NCI Deputy Director Dr. Anna Barker. “Certain tumors are going to be difficult to collect and analyze, but this study—which used high-quality samples and multidimensional data—now gives the community new opportunities to understand the disease.”

The researchers sequenced 157 genes that were known to be associated with prostate and other cancers. Mutations in these genes were rare. But when the researchers included additional information, such as DNA copy-number changes (gains and losses of DNA), they identified several genetic pathways, including the PI3K pathway, that were altered in nearly all metastatic tumors and many primary tumors.

“Just as we’ve seen in brain tumors, when you combine all these different sources of information, there is a uniform consistency of pathways that are altered in the disease,” said co-author Dr. Peter Scardino, chairman of the Department of Surgery at MSKCC. “We found many more abnormalities in localized prostate cancer than we expected.”

The researchers also identified a gene called NCOA2 that appears to play an important role in about 11 percent of prostate tumors. The protein encoded by this gene may drive prostate cancer by amplifying signals from the androgen-receptor pathway; this pathway plays a critical role in early- and late-stage prostate cancer.

Potential Biomarker

The analysis also revealed a striking association between changes in DNA copy number and the risk of recurrence after surgery, and this association could not be explained entirely by Gleason score. “This was one of the most exciting findings from the study,” said Dr. Scardino. “It offers the possibility of a biomarker that could be used to characterize the aggressiveness of prostate cancer, which is something we greatly need.”

Doctors currently do not have a way to distinguish between prostate cancers that require aggressive treatment and those that will cause no harm if left alone. Consequently, many men receive treatment unnecessarily. Genomic tests can provide prognostic information in breast cancer, for example, but none yet exists in this disease.

The new findings, if confirmed, represent a prototype for developing these kinds of prognostic tests for prostate cancer, said Dr. Jonathan Simons, CEO and president of the Prostate Cancer Foundation. “This would change how doctors talk to patients about the disease and the need for adjuvant therapy or not, which is why this finding is so exciting,” he added.

Dr. Scardino runs the Specialized Program of Research Excellence (SPORE) in prostate cancer at MSKCC, and his group has launched follow-up studies. The current work was done using frozen tumor specimens collected during prostatectomies. The researchers will now see whether copy-number changes are informative using paraffin-embedded tissues. If the answer is yes, they will test cells obtained from a needle biopsy.

The genome analysis also revealed that some patients whose tumors include a fusion of the genes TMPRSS2 and ERG are also missing part of chromosome 3. This fusion gene occurs in about half of all prostate cancers, and researchers have suspected that other genes also play a role in these cases.

“This deletion on chromosome 3 appears to be very strongly associated with the fusion,” said Dr. Sawyers. “The next steps are to see which genes in the region that is deleted are involved in the disease. We have a clear path forward.”

The TMPRSS2-ERG fusion was discovered in 2005 by University of Michigan researchers supported by NCI’s Early Detection Research Network. At the time, fusions were thought to be limited to cancers of the blood, but it is now known that these alterations are present in common cancers as well. About two dozen have been identified in prostate cancer.

New Class of Gene Fusions

Earlier this month, the Michigan group, led by Dr. Arul Chinnaiyan, reported a new class of prostate cancer gene fusions derived from the RAF pathway. One of these fusions involves the gene BRAF, which plays a role in melanoma. Drugs targeting BRAF are in clinical trials, and it appears, based on experiments in cells, that these drugs may be active in up to 2 percent of patients with prostate cancer, the researchers reported.

“The clinical promise of this discovery is that patients who have these RAF gene fusions may be candidates for drugs that target these changes,” said Dr. Chinnaiyan. “Some of the newer inhibitors, in particular, might be useful in treating this molecular subtype of prostate cancer as well as some other cancers.”

In the future, every man whose prostate cancer is biopsied is going to have his DNA read for gene fusions, just as women have their breast cancers tested for overexpression of the HER2 protein to determine whether they should receive trastuzumab (Herceptin), predicted Dr. Simons. “To cure every man of advanced prostate cancer, we’ll need at least 24 strategies,” he continued. “Now that we know what we’re facing, we can make research plans and do the work.”

Two prostate cancer genome sequences have been presented at scientific meetings and will likely be published later this year, Dr. Simons said. “It’s a complicated disease, but key properties of the disease are going from being in total darkness to full clarity. And that’s what is so amazing.”

For Dr. Barker, a founder of The Cancer Genome Atlas (TCGA) project with colleagues from the National Human Genome Research Institute, the MSKCC study is both exciting and gratifying. Dr. Sawyers and his colleagues essentially followed the TCGA approach by profiling high-quality tumor samples and integrating clinical and multiple kinds of genomic information into their analysis. As with TCGA, they made the results public so that investigators in the community can now mine the information for new insights.

The hope from the beginning of TCGA has been that the approach would be adopted by investigators performing cancer genomics studies in the community, said Dr. Barker. And now that this study has been completed, TCGA investigators will use the data when they launch an even larger study of prostate tumors in the future.

“This study gives us a much better starting point for prostate cancer than we’ve ever had before,” Dr. Barker said. “It’s a great day for cancer research, and an even better day for patients.”

—Edward R. Winstead

Discovery Of A Piece Of The Puzzle For Individualized Cancer Therapy Via Gene Silencing

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Posted 01 Jun 2010 — by James Street
Category General Cancer Research, genetic research

28 May 2010

In a major cancer-research breakthrough, researchers at the McGill University, Department of Biochemistry have discovered that a small segment of a protein that interacts with RNA can control the normal expression of genes – including those that are active in cancer.

The research, published online on May 26, 2010 by the prestigious journal Nature, has important immediate applications for laboratory research and is another step toward the kind of individualized cancer therapies researchers are pursuing vigorously around the world.

Human cells need to produce the correct proteins at the right time and in the appropriate quantities to stay healthy. One of the key means by which cells achieve this control is by “RNA interference”, a form of gene silencing where small pieces of RNA, called micro RNAs, obstruct the production of specific proteins by interacting with their genetic code. However, not any piece of RNA can do this. Dr. Bhushan Nagar and graduate student Filipp Frank, in collaboration with Dr. Nahum Sonenberg at McGill’s new Life Sciences Complex, used structural biology to unravel how a small segment in the Argonaute proteins, the key molecules of RNA interference, can select the correct micro RNAs.

In doing so, the team has discovered that Argonaute proteins can potentially be exploited to enhance gene silencing. “RNA interference could be used as a viable therapeutic approach for inhibiting specific genes that are aberrantly active in diseases such as cancer”, Nagar said. “We now have a handle on being able to rationally modify micro RNAs to make them more efficient and possibly into therapeutic drugs.”

While therapeutic applications are many years away, this new insight provides an avenue to specifically control the production of proteins, which in cancer cells for example, are abnormal.

“This is fantastic news,” said Dr. David Thomas, Chair of McGill’s Department of Biochemistry. “You’ve seen stories lately about how we may see the end of chemotherapy? Well, this is part of that path in developing genetically based therapies that can be tailored to individual patients’ particular illnesses. It’s a great step forward.”

The research received funding from the Canadian Institutes of Health Research, the Human Frontier’s Science Program and supported by the FRSQ Groupe de Recherche Axé sur la Structure des Protéines (GRASP).

Source:
William Raillant-Clark
McGill University

Article URL: http://www.medicalnewstoday.com/articles/190125.php

Main News Category: Cancer / Oncology

Also Appears In:  Genetics,

correlation of RUNX2 overexpression with poor response to chemotherapy

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Posted 13 May 2010 — by James Street
Category genetic research

Research article

Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy

Bekim Sadikovic email, Paul Thorner email, Susan Chilton-MacNeill email, Jeff W Martin email, Nilva K Cervigne email, Jeremy Squire email and Maria Zielenska email

BMC Cancer 2010, 10:202doi:10.1186/1471-2407-10-202

Published: 13 May 2010

Abstract (provisional)

Background

Human osteosarcoma is the most common pediatric bone tumor. There is limited understanding of the molecular mechanisms underlying osteosarcoma oncogenesis, and a lack of good diagnostic as well as prognostic clinical markers for this disease. Recent discoveries have highlighted a potential role of a number of genes including: RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B, BMP2, HISTH2BE, FOS, CCNB1, and CDC5L.

Methods

Our objective was to assess relative expression levels of these 16 genes as potential biomarkers of osteosarcoma oncogenesis and chemotherapy response in human tumors. We performed quantitative expression analysis in a panel of 22 human osteosarcoma tumors with differential response to chemotherapy, and 5 normal human osteoblasts.

Results

RECQL4, SPP1, RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A, RB1, P53, and LSAMP showed significant loss of expression relative to normal osteoblasts. In addition to being overexpressed in osteosarcoma tumor samples relative to normal osteoblasts, RUNX2 was the only gene of the 16 to show significant overexpression in tumors that had a poor response to chemotherapy relative to good responders.

Conclusion

These data underscore the loss of tumor suppressive pathways and activation of specific oncogenic mechanisms associated with osteosarcoma oncogenesis, while drawing attention to the role of RUNX2 expression as a potential biomarker of chemotherapy failure in osteosarcoma.

Location of original article

Platinum-based cancer drugs (cisplatin) destroy tumor cells by binding to DNA strands

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Posted 14 Apr 2010 — by James Street
Category Mouse Osteosarcoma Studies, genetic research

Platinum-based cancer drugs destroy tumor cells by binding to DNA strands

April 14, 2010 by Anne Trafton

For 30 years, the chemotherapy drug cisplatin has been one of doctors’ first lines of defense against tumors, especially those of the lung, ovary and testes. While cisplatin is often effective when first given, it has a major drawback: Tumors can become resistant to the drug and start growing again.

Now, MIT cancer biologists have shown how that resistance arises, a finding that could help researchers design new drugs that overcome resistance. The team, led by Tyler Jacks, director of the David H. Koch Institute for Integrative Cancer Research at MIT, reports the results in the April 15 issue of the journal Genes and Development.

Cisplatin and other platinum-based cancer drugs destroy by binding to DNA strands, interfering with . That activates the cell’s DNA repair mechanisms, but if the damage is too extensive to be repaired, the cell undergoes programmed suicide.

Eventually, learn to fight back. The new study shows that tumor cells treated with cisplatin ramp up their DNA repair pathways, allowing them to evade cell death, says Trudy Oliver, a postdoctoral fellow in Jacks’ lab and lead author of the paper.

Previous studies had suggested several possible mechanisms for resistance development, including enhancement of DNA repair pathways, detoxification of the drug, and changes in how the drug is imported into or exported out of the cell. However, those studies were done in cancer cells grown in the lab, not in living animals (in vivo).

“Many mechanisms have been identified but it’s not clear what happens in vivo because the in vivo environment is so much more complicated than in cell lines,” says Oliver.

Oliver and her colleagues set out to study cisplatin resistance in mice with a mutation in a gene called Kras, which leads the animals to develop lung cancer. About 30 percent of human lung cancer patients have mutations in Kras. Some of the mice also had defective versions of the tumor suppressor , which is mutated in about half of human lung cancers.

The researchers found that cisplatin was effective against lung tumors in both sets of mice, though it was more potent in mice that still had functional p53. In those mice, tumors actually shrank, while the drug only slowed tumor growth in mice with defective p53. Those results are consistent with findings in human patients.

After four doses of cisplatin, mice with normal p53 developed resistance to the drug, and tumors started growing faster. To figure out why, the researchers analyzed which genes were being transcribed more as resistance developed, and identified several that are involved in DNA repair pathways.

One gene that particularly caught the researchers’ attention is PIDD (p53-induced protein with a death domain), which is turned on by p53 and has been implicated in programmed cell death, though its exact function is not known. When PIDD levels are artificially increased in human lung cancer cells, they become more resistant to cisplatin.

Oliver is now studying tumors in which the PIDD gene has been knocked out, to see if its absence hinders drug resistance. It is likely that PIDD is just one of many genes, in many pathways, involved in the drug resistance process, says Oliver. “It’s not a simple phenomenon,” she says.

More information: “Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer,” Trudy Oliver, Kim Mercer, Leanne Sayles, James Burke, Diana Mendus, Katherine Lovejoy, Mei-Hsin Cheng, Aravind Subramanian, David Mu, Scott Powers, Denise Crowley, Roderick Bronson, Charles Whittaker, Arjun Bhutkar, Stephen Lippard, Todd Golub, Juergen Thomale, Tyler Jacks and Alejandro Sweet-Cordero; Genes and Development.

Provided by Massachusetts Institute of Technology (news : web)

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Rational Therapeutics, Inc. Personalized Cancer Treatment

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Posted 07 Apr 2010 — by James Street
Category Human osteosarcoma research

Rational Therapeutics is dedicated to identifying unique characteristics of each cancer subtype, such as osteosarcoma, to enable oncologists to treat them with targeted therapies.

Rational Therapeutics is directed by Dr. Robert A. Nagourney.

Patients their oncologists can find out more about Dr. Nagourney’s work at:

Rational Therapeutics

Rational Theapeutics is located at:

750 E 29th St., Long Beach, CA 90806, United States

(562)989-6455, (562)989-8160 fax,

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inactivation of SMO may be a useful approach to the treatment of patients with osteosarcoma

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Posted 16 Mar 2010 — by James Street
Category genetic research

The Hedgehog signaling pathway functions as an organizer in embryonic development. Recent studies have demonstrated constitutive activation of Hedgehog pathway in various types of malignancies.

However, it remains unclear how Hedgehog pathway is involved in the pathogenesis of osteosarcoma. To explore the involvement of aberrant Hedgehog pathway in the pathogenesis of osteosarcoma, we investigated the expression and activation of Hedgehog pathway in osteosarcoma and examined the effect of SMOOTHENED (SMO) inhibition.

Results: To evaluate the expression of genes of Hedgehog pathway, we performed real-time PCR and immunohistochemistry using osteosarcoma cell lines and osteosarcoma biopsy specimens.

To evaluate the effect of SMO inhibition, we did cell viability, colony formation, cell cycle in vitro and xenograft model in vivo. PCR revealed that osteosarcoma cells over-expressed Hedgehog, PTCH, SMO, and GLI.

Real-time PCR revealed over-expression of SMO, PTCH, and GLI2 in osteosarcoma biopsy specimens’. These findings showed that Hedgehog pathway is activated in osteosarcomas.

Inhibition of SMO by cyclopamine, a specific inhibitor of SMO, slowed the growth of osteosarcoma in vitro. Cell cycle analysis revealed that cyclopamine promoted G1 arrest.

Cyclopamine reduced the expression of accelerators of the cell cycle including cyclin D1, cyclin E1, SKP2, and pRb. On the other hand, p21cip1 protein was up-regulated by cyclopamine treatment.

In addition, knockdown of SMO by SMO shRNA prevents osteosarcoma growth in vitro and in vivo.

Conclusions: These findings suggest that inactivation of SMO may be a useful approach to the treatment of patients with osteosarcoma.

Author: Masataka HirotsuTakao SetoguchiHiromi SasakiYukihiro MatsunoshitaHui GaoHiroko NagaoOsamu KunigouSetsuro Komiya
Credits/Source: Molecular Cancer 2010, 9:5

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Researchers find powerful predictor of bone cancer prognosis

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Posted 16 Mar 2010 — by James Street
Category genetic research

Researchers find powerful predictor of bone cancer prognosis
January 7, 2010

(PhysOrg.com) — Scientists at the University of Toronto and The Hospital for Sick Children (SickKids) have discovered a powerful new tool that can help predict the prognosis for patients with bone cancer and help doctors more accurately determine how aggressively they need to treat specific patients. They found that the presence of a specific type of genetic mutation found in the tumours results in poorer outcomes for patients with osteosarcoma – the most common bone cancer in children and adolescents. The study is published in the current issue of Cancer Research.

The research team analyzed tumour DNA from osteosarcoma patients and found a novel region called osteo3q13.31, which contains three genes that were previously not known to be involved in the disease. They used the presence or absence of a mutation in these genes – known as an osteo3q13.31 deletion – as an indicator to predict the disease outcome in osteosarcoma. They studied 49 patients and found that a deletion resulted in poorer outcomes.  (No statistics were released to the hoi polloi because they might be shocked and experience stress by the bad news –editor.)

“This marker is an incredibly powerful tool. If the deletion is present, this suggests that the patient would need more aggressive therapy than if it is absent,” says principal investigator Dr. David Malkin, Paediatric Oncologist and Senior Scientist at SickKids, and Professor in the Department of Paediatrics at the University of Toronto. “Hopefully, we would be able to avoid over treating patients who don’t need the most aggressive therapy, while ensuring that we aren’t under treating those who do.”

The advent of high-resolution technologies allowed the scientists to look at regions of DNA with much more clarity. The scientists used a high-resolution tool called single-nucleotide polymorphism (SNP) array to look at copy number alteration (CNA). CNA is a genetic phenomenon that occurs when some regions of the DNA are duplicated or deleted. Normally genes are present in two copies, with one copy inherited from each parent. CNAs are often found in osteosarcoma.

Every year, there are about 300 new cases of osteosarcoma in Canada, most of which occur in adolescents and young adults. The survival rate of about 65 per cent has not changed in about two decades. While the first step is to use the new marker as a prognostic tool, Malkin says it may eventually be used as a therapeutic target, ultimately leading to improved survival rates for osteosarcoma. Down the road, the marker may also be able to help determine prognosis in tissue cancers including carcinomas and sarcomas, he explains.

The research was supported by the Canadian Institutes of Health Research and SickKids Foundation.

Provided by University of Toronto (news : web)

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longest disease-free interval between primary diagnosis and metastatic recurrence of an osteosarcoma, 21 years

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Posted 16 Mar 2010 — by James Street
Category Human osteosarcoma research

To the best of our knowledge, this case report describes the longest disease-free interval between primary diagnosis and metastatic recurrence of an osteosarcoma.

Case presentation. A 35-year-old Caucasian American man presented with asymptomatic lung metastases 21 years after being diagnosed and treated for lower extremity osteosarcoma. He underwent curative lung resection, but 2 years thereafter developed metastatic disease in the scapula and tibia and, after resection and chemotherapy, is in remission 1 year later.

Conclusion: This case highlights the importance of long follow-up periods and continued surveillance of osteosarcoma patients after initial curative treatment.

Author: Ari HalldorssonSteven BrooksSam MontgomerySuzanne Graham
Credits/Source: Journal of Medical Case Reports 2009, 3:9298

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