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5 (2 votes)

Healthcare Prof:

Article Opinions:1 posts
Researchers in the Walter and Eliza Hall Institute have discovered that breast stem cells are exquisitely sensitive towards the female hormones oestrogen and progesterone, a discovering that opens the way for the development of new preventions and treatments for breast cancer.

The discovery, by scientists in the institute’s Stem Cells and Cancer and Bioinformatics divisions, also explains decades of evidence linking breast cancer risk to exposure to female hormones.

It has been published on the web inside the international journal Nature.

Dr Jane Visvader, who led the research with Dr Geoff Lindeman, said sustained exposure to oestrogen and progesterone was a well-established threat factor for breast cancer. “There is really a clear evidence that the far more menstrual cycles a woman has the higher her breast cancer risk,” Dr Visvader said. “There is even an improve in breast cancer threat within the short-term following pregnancy. Even so the cellular basis for these observations has been poorly understood.”

In the mid-2000s, Drs Visvader and Lindeman discovered breast stem cells in each mice and humans. Unexpectedly, even so, they also located that breast stem cells lacked ‘receptors’ that would allow them to be directly controlled by the female hormones oestrogen and progesterone.

Now, perform by Drs Visvader and Lindeman in collaboration with Drs Marie-Liesse Asselin-Labat, Gordon Smyth and other people at the institute, has revealed that in spite of lacking receptors for oestrogen and progesterone, breast stem cells are still remarkably sensitive to female hormones.

Using mouse models, they showed that when the ovaries were removed or the animals were treated with hormone inhibitors (that are in clinical use as anti-breast cancer agents), breast stem cell numbers dropped and also the cells appeared to become dormant.

Dr Lindeman, who is also a medical oncologist in the Royal Melbourne Hospital, said this finding helped to explain why the effects of ‘chemoprevention’ – a remedy aimed at breast cancer prevention continued lengthy following anti-estrogen tablets have been stopped.

“Our research also revealed that for the duration of pregnancy there is a profound boost in breast stem cell numbers,” Dr Lindeman stated.

“This may account for the short-term enhance in cancer threat related to pregnancy.”

Further studies, in collaboration with Dr Jack Martin at St Vincent’s Institute Melbourne and Dr Hisataka Yasuda in the Nagahama Institute for Biochemical Science, identified the RANK ligand pathway as the key cell-signalling pathway responsible for the indirect control of breast stem cells in pregnancy.

Dr Lindeman said inhibitors of RANK signalling have been developed and are at the moment in clinical trials to help preserve bone strength and treat breast cancer that has spread to the bones. “Our discovery suggests that inhibitors of RANK or other stem cell pathways represent achievable therapeutic techniques that could also be investigated as breast cancer prevention agents,” Dr Lindeman stated.

The study was supported by the Victorian Breast Cancer Study Consortium / Victoria Cancer Agency, Susan G. Komen Foundation, National Breast Cancer Foundation, National Health and Medical Analysis Council, and also the Australian Cancer Investigation Foundation.

Source:
Penny Fannin
Walter and Eliza Hall Institute

four.33 (3 votes)

Healthcare Prof:

ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP), announced it has initiated a Phase I/II study at Memorial Sloan-Kettering Cancer Center for the novel, mathematically – determined administration of oral indibulin (Zybulin? or ZIO-301) in the therapy of metastatic breast cancer.

The Phase I trial is expected to enroll approximately 20 patients and will determine the maximum tolerated dose of oral indibulin implementing the “mathematically modeled” dose administration schedule – 5 days on and 9 days off – that capitalizes on the convenience of oral administration, but also maximizes drug activity, limiting potential toxicity and resistance.

Indibulin is a novel, oral tubulin binding agent that targets both mitosis and cancer cell migration. It is expected to have several potential benefits, including oral dosing, application in multi-drug resistant tumors, no neuropathy, and minimal overall toxicity. In multiple Phase I trials, oral indibulin has been administered both as a single agent and in combination with favorable activity, and has a promising safety profile that does not include the neurotoxicity seen with all of the other classes of tubulin binding agents. The trial will be continued into Phase II once dose has been established in Phase I.

Clifford A. Hudis, M.D., Chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center, noted, “The development of an additional new therapy for breast cancer that is effective but with fewer of the far more significant side effects related to many commonly used therapies would be an important step in the treatment of this disease. We look forward to testing this novel agent and dosing schedule in patients.”

The study will implement a mathematically modeled drug administration schedule that was developed in preclinical studies by Larry Norton, M.D. as a consultant to ZIOPHARM Oncology, Inc. The model capitalizes on the convenience and scheduling flexibility of oral administration to maximize anticancer activity, minimize potential toxicity and resistance, and exploit the drug’s mechanisms of action on each cancer cell division and cell movement. Findings from the preclinical studies had been presented at the 2009 American Society of Clinical Oncology annual meeting.

Memorial Sloan-Kettering’s Breast Cancer Medicine team, under the direction of Dr. Hudis, has successfully translated preclinical perform into meaningful clinical treatment in past studies, and will lead this Phase I/II trial.

For much more details about this trial, please see http://www.clinicaltrials.gov.

Source
ZIOPHARM Oncology, Inc.

four.5 (four votes)

Healthcare Prof:

4.five (two votes)

The case of a 45-year old man from Marion, North Carolina, in the US, whose parents each had breast cancer and, when he suspected he was getting symptoms himself, was turned away by a local public wellness clinic that offers free breast screening because he is a man, has highlighted the plight of men who may be at risk of the disease: dealing with a system that appears to assume only women get breast cancer.

According to ABC News, Scott Cunningham has been vigilant about his health since both his parents had been diagnosed with breast cancer within the 1990s. He says he now has the same symptoms that his father had: lumps under his nipple that feel like “knots”, he feels “different” and tired all the time.

He had not done anything about it for several months because he was uninsured and unemployed after losing his job at a furniture factory.

Eventually, as the symptoms got worse, he decided he would call a local health clinic that offered free mammograms, but when he contacted them they stated he was not eligible because he was a man as well as the clinic only served women.

Cunningham was turned away by the Rutherford-Polk-McDowell Health District’s National Breast and Cervical Cancer Early Detection Program, which is funded by the Centers for Disease Manage and Prevention (CDC), and only serves women, aged 40 to 60.

Helen White, a clinical nursing supervisor at the Rutherford-Polk-McDowell Health Department, stated it was true that federal breast screening funds are limited to women, but added they would do everything they could to assist Cunningham.

She said like any other situation, it would depend on whether he had insurance, Medicaid (the government insurance scheme for people on low income), or was eligible on low income grounds.

“We would refer him to a couple of options, a free clinic within the county, or Well being Plus, which is a sliding scale in the hospital — whether he was male or female,” White told ABC News.

Cunningham stated he was stunned and confused when they told him they only offered screening to women. He had assumed that while it was once thought to be just a woman’s cancer, it was well known that men can also get it.

White has now been in contact with Cunningham and offered him help to find another clinic.

According towards the National Cancer Institute, compared to occurrence in women, male breast cancer is rare: less than 1 per cent of all cases are in men. Last year inside the US, there had been an estimated 1,910 cases of breast cancer in men, and 440 deaths, compared with 192,370 cases and 40,170 deaths among women with the disease.

The average age for breast cancer diagnosis in men is between 60 and 70, but it can occur at any age.

Risk factors include: exposure to radiation, estrogen, and diseases linked to having excessive amounts of estrogens in the body, such as cirrhosis or Klinefelter syndrome. Family history is thought to be a factor, especially where many female relatives have had the disease, and where it involves the BRCA2 gene mutation.

The NCI says that overall chances of survival is similar to that of women, along with the impression that men have a worse prognosis is probably due to the fact they don’t receive an early diagnosis.

Among many reasons given for men receiving a later diagnosis is that they are not sufficiently aware that they could be susceptible to breast cancer.

However, as this case demonstrates, it could be that there’s also a need for higher awareness within the public well being system so screening and support is as widely available for men as for women.

Last year, Peter Criss, the 63-year old ex drummer and founding member of rock band KISS spoke in public about his breast cancer.

Criss said that thanks to an early diagnosis he was successfully treated for breast cancer in 2008. He urged men to be aware that breast cancer was not an exclusively female disease and if they spot a lump they should not be ashamed and go to the doctor straight away.

In the case of Scott Cunningham and his father, they said they had been not put off by the stigma of it being a “female disease”. They said they had been not bothered by those stereotypes.

“Some men would hang their heads, but no way, I am a man,” said Cunningham.

Related write-up:

Medical News Today, Ex Drummer Of Rock Band KISS Speaks In Public About His Breast Cancer, 22 October 2009.

Source: ABC News, MNT Archives, NCI.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

5 (1 votes)

Healthcare Prof:

A statewide program offered through the Alabama Department of Public Well being provides free breast and cervical cancer screenings for women who are unable to pay for a mammogram or a pap smear.

To qualify for the free services, women must

- Be ages 40 through 64
- Have a family income at or below 200 percent of federal poverty guidelines
- Have no insurance or be underinsured

For example, a single woman may have an income of up to $21,660 per year to be eligible while a woman in a family of four may have an annual income of up to $44,100 to qualify. Underinsured means a woman is unable to pay a high deductible or her wellness insurance does not include screenings.

“It is becoming common knowledge that early cancer screening, early detection, saves lives,” stated Nancy Wright, director of the Cancer Prevention and Control Division. “This is especially true for breast and cervical cancer. Early cancer screening may seem impossible to women without insurance–but it’s not. We urge Alabama women to make a screening appointment today.”

The Alabama Breast and Cervical Cancer Early Detection program (ABCCEDP) was created to assist low income, uninsured and underinsured women receive free breast and cervical cancer screening so these cancers can be detected early. Free services include a pelvic examination, pap smear, clinical breast examination, mammogram and diagnostic services.

If follow-up is needed, the program will pay for diagnostic testing such as an ultrasound, biopsy or colposcopy. If a woman is diagnosed with cancer, the program will refer her to Medicaid for treatment of breast or cervical cancer.

Since 1996, the program has provided screenings for nearly 70,000 women. Of these, 1,200 women had been diagnosed with breast cancer and 320 with cervical cancer. In addition, any woman under 64 who has been recently diagnosed with breast or cervical cancer may be eligible for therapy through Medicaid.

“Discovering breast cancer early will increase your chance of survival,” Ms. Wright said. “The earlier the stage it is detected, the far more successfully it can be treated. When breast cancer is diagnosed early, the survival rate is over 95 percent. But this figure declines dramatically when cancer is identified in later stages.”

Source
Alabama Department of Public Health

Healthcare Prof:

The groundbreaking algorithms developed at TechniScan, Inc. (OTC Bulletin Board: TSNI) have led to a new arena of whole breast ultrasound technology, as presented at a national medical ultrasound conference in San Diego in March.

TechniScan cofounder and scientist-mathematician, James Wiskin, Ph.D. spoke at the American Institute of Ultrasound Medicine (AIUM) conference held at the San Diego Marriott Hotel and Marina about the unique methods in which the company’s 3-dimensional whole breast ultrasound captures anatomical images of the breast.

The breakthrough in imaging is really a result of Wiskin’s and colleagues David Borup, Ph.D., and Steven Johnson’s, Ph.D. perform inside the mathematics of inverse scattering. TechniScan’s Warm Bath Ultrasound? (WBU) system uses a unique combination of traditional B-mode (reflective) ultrasound and two types of transmission ultrasound speed of sound and attenuation of sound, to produce three unique sets of images.

“This revolutionary new method of imaging produces information not available with traditional reflection ultrasound or whole breast ultrasound as it is presently being developed. Uniquely, we can also capture 360 degree compounded coronal images,” stated Wiskin.

The goal of the new technology is to improve breast imaging and provide tissue characterization that will much more accurately distinguish pathological from normal breast tissue. The images are captured in a comfortable, radiation-free method as a woman lies prone on an examination table and ultrasound is directed, making use of warm water as a coupling medium, into the patient’s breast tissue.

“Our quantitative, high-resolution, speed of sound and attenuation estimates are unique to whole breast ultrasound and have the potential to deliver new diagnostic tools to radiologist. There are many achievable applications for our technology and we are looking forward to collaborating with the medical community and breast analysis centers internationally,” said Wiskin.

Wiskin is really a co-inventor of the fundamental imaging algorithms used by TechniScan to produce whole breast ultrasound images. His research includes inverse scattering theory, image processing, and acoustic, electromagnetic, and elastic wave propagation. His dissertation in the University of Utah (mathematics) established new inverse scattering imaging methods. He at the moment holds a faculty position within the Department of Bioengineering at the University of Utah.

About TechniScan, Inc.

Based in Salt Lake City, TechniScan, Inc. is really a medical device company engaged inside the development and commercialization of a non-invasive imaging tool designed to provide physicians with automated ultrasound images of the human breast. The Warm Bath Ultrasound system simultaneously collects both transmission and reflection ultrasound images in the course of a single scanning examination. TechniScan’s WBU imaging device is limited by U.S. law to investigational use unless, and until, cleared by the FDA.

Source: TechniScan, Inc

Healthcare Prof:

African-American women have poorer survival rates than their white and Hispanic counterparts regardless of whether they receive radiation therapy following lumpectomy or mastectomy, UC Davis researchers have discovered.

Steve Martinez, assistant professor of surgery at UC Davis Cancer Center, determined that while Hispanic and African-American women with advanced breast cancer are less likely to receive radiation therapy than their white counterparts, only African Americans have poorer outcomes than white patients with the same stage disease.

The findings, presented in Washington, D.C., in the Association for Clinical Research Training as well as the Society for Clinical and Translational Science meeting, suggest that the lack of radiation therapy treatment is not responsible for the poorer survival noted among African-American patients.

“Is this a biological difference?” Martinez asks. “Do black patients benefit from post-surgery radiation therapy towards the degree that Hispanics and whites benefit?”

These questions are part of Martinez’ ongoing exploration of cancer well being disparities as they affect patients’ response to therapy and overall survival. A surgical oncologist, Martinez is one of many clinicians at UC Davis Cancer Center who also are locating ways to address the disproportionate cancer burden for certain patient populations.

The current study is one of two Martinez undertook to examine factors influencing survival for breast cancer patients. Within the first, he looked at data from much more than 12,000 women from throughout the country who had breast cancer that had spread to 10 or a lot more lymph nodes and that had resulted in either lumpectomy or mastectomy.

“By definition, all of these patients should get radiation therapy,” he said.

What he located was that Hispanic patients were 20 percent less likely to get radiation therapy than their white counterparts, and black patients were about 24 percent less likely to receive radiation therapy.

For the second study, he wanted to learn whether the disparities in receipt of radiation therapy resulted in poorer outcomes for Hispanic and African-American women.

“That is not what we discovered,” he said. “Hispanic patients had been not significantly different from white patients in overall survival rates, but black patients did worse. This survival disparity seen in black patients was unrelated to whether or not they received radiation therapy as part of their treatment.”

Martinez examined 10-year survival rates in patients from each group who received radiation therapy and those who did not. While he located dramatic differences in survival for white women who had radiation therapy (an 11 percent survival boost), black patients had just a 3 percent difference in their survival rates.

Martinez plans to continue his research into factors that may influence whether or not patients receive radiation therapy and that may also affect their outcomes, including feasible biological differences.

“We are trying to see which remedies perform best for which people,” he stated. “Ultimately, we can figure out treatments that may work well for you, but not for someone else. This is a step on that path.”

Source:
Dorsey Griffith
University of California – Davis – Health System

Healthcare Prof:

1. Survivors of Childhood Cancer Face Shortened Life Expectancy in Adulthood

Due to advances in remedy, five-year survival rates for childhood cancer have risen to approximately 80 percent. As the population of long-term survivors continues to grow, health care providers will need to understand the late effects of cancer and its remedies on survivor’s long-term wellness. Researchers developed a computer model to estimate the cumulative effect of disease- and treatment-related mortality threat for persons aged 15 years who had survived at least 5 years after receiving remedy for childhood cancer. The researchers located that survivors of childhood cancers face wellness risks that shorten their life span by about 10 years on average. The loss in life expectancy varied for different types of cancer. Survivors of kidney cancer died about 4 years earlier, whereas survivors of bone and brain cancer died about 18 years earlier than the general population. The researchers suggest that use of treatment agents with late toxicities used in previous decades could be to blame. The authors of an accompanying editorial conclude that physicians should consider the complexity of past remedies and their long-term and late effects when caring for these patients. “The important role of prevention and wellness promotion in this patient population should not be underestimated. Caring for the whole patient is essential, including the psychological needs that arise with the burden of living with a chronic disease,” they write.

2. Early, Lifelong Surveillance for Breast Cancer Recommended for Young Women Treated with Chest Radiation

Studies consistently show that chest radiation is associated with an excess risk for breast cancer. Researchers reviewed available data to summarize breast cancer danger and breast cancer surveillance in women right after chest radiation for pediatric or young adult cancer. They found that women in this population have a substantially elevated threat for breast cancer at a young age, which does not seem to plateau. Since breast cancer outcomes right after diagnosis are similar to those within the general population, early detection is beneficial. Nevertheless, women in this patient population have fewer treatment options for breast cancer because of therapy exposures used to cure their first cancer. The evidence suggests that MRI plus mammography beginning at age 25 may be the best way to screen these women for breast cancer, but much more investigation is needed to weigh the potential benefits and harms of the additional radiation exposure. Estimates of benefits and risks may change over time given use of lower radiation doses in contemporary remedies.

3. Your Social Network May Affect Your Drinking Habits

According to a study published in Annals of Internal Medicine, the flagship journal of the American College of Physicians, the drinking habits of the people in your extended social group play a major role in determining your own rate of alcohol consumption.

Researchers used data from the landmark Framingham Heart Study which followed 12,067 people for a lot more than 30 years and helped to define the patterns in social networks of other wellness issues such as obesity, smoking, and sexually transmitted diseases. In this analysis, the researchers sought to explore patterns of alcohol use in a large social network.

“We’ve located that the influence of your friends and people you have connections with can affect your wellness just as much as your family history or your genetic background,” said Nicholas Christakis, MD, PhD, Professor of Medicine at Harvard University and lead author of the study. “With regard to alcohol consumption, your social network may have both positive and negative wellness consequences, depending on the circumstances.”

In the study, self-reported alcohol intake over time followed changes inside the alcohol intake of the respondents’ social contacts. The researchers discovered that a person was 50 percent a lot more likely to drink heavily if a person they are directly connected with also drinks heavily and 36 percent a lot more likely to drink heavily if a friend of a friend drinks heavily. The impact extended up to three degrees of separation. The researchers suggest this social phenomena could have other implications for clinical and health interventions. Social networks could be used to exploit positive wellness behaviors and further support group interventions.

“Our findings reinforce the idea that drinking can be a public health and clinical problem that involves groups of interconnected people who evince shared behaviors,” said Christakis. “In treating individuals for problematic drinking, we need to look at their social networks to identify and eliminate obstacles to abstaining.”

4. Elderly Patients on Antipsychotic Drugs at Increased Threat for Community-acquired Pneumonia

Both atypical and typical antipsychotic drugs are widely used to treat geriatric psychiatric disorders, including dementia. Even so, experts have questioned the safety profile of these drugs as increased mortality (mostly due to pneumonia) has been reported in elderly dementia patients who were treated with antipsychotics. Dutch researchers conducted a nested case-control study of elderly, community-dwelling patients who received a prescription for an antipsychotic drug between 1996 and 2006. Compared with past use, current use of either atypical or typical antipsychotic drugs was associated with a dose-dependent boost in threat for fatal or nonfatal community-acquired pneumonia. The highest danger period was the first week of therapy. Researchers recommend that physicians closely monitor patients, particularly in the beginning of therapy, and if patients are on a high dose.

Source:
Angela Collom
American College of Physicians

four (1 votes)

Healthcare Prof:

5 (1 votes)

Women with breast cancer before age 55 who carry an inherited mutation within the breast cancer susceptibility genes BRCA1 or BRCA2 are four times much more likely to develop cancer inside the breast opposite, or contralateral, to their initial tumor as compared to breast cancer patients without these genetic defects. These findings, by Fred Hutchinson Cancer Analysis Center breast cancer epidemiologist Kathleen Malone, Ph.D., and colleagues, were published online April five in the Journal of Clinical Oncology.

Compared to non-carriers, breast cancer patients with a BRCA1 mutation had a 4.5-fold increased threat and those with a BRCA2 mutation had a three.4-fold increased threat of a subsequent contralateral breast cancer, the researchers identified. Carriers of either mutation who had been diagnosed with breast cancer before age 55 faced an 18 percent cumulative probability of developing cancer inside the opposite breast within 10 years as compared to a 5 percent cumulative probability among women who had been mutation-free.

In addition, the study revealed that among those who harbored a BRCA1 mutation, the younger they were at the time of initial diagnosis the higher was their risk of developing contralateral breast cancer. For example, mutation carriers diagnosed initially in their early to mid 30s had a 31 percent cumulative probability of developing contralateral breast cancer within 10 years as compared to a 7 percent probability among non-carriers.

“For young women with breast cancer, our results reinforce the message that early-onset disease is much more likely to be related to a BRCA mutation,” said Malone, first author of the paper and a member of the Public Well being Sciences Division in the Hutchinson Center.

While only about 5 percent of breast cancer patients across all age groups carry a BRCA mutation, the younger a woman is in the time of her first breast cancer diagnosis, the a lot more likely she is to have such a mutation. “In the youngest patients in our study those with a first cancer diagnosed before age 35 we discovered that 16 percent of those with one breast tumor and 54 percent of those who had developed two primary breast cancers carried a mutation,” Malone said. Mutation frequencies had been elevated also in women diagnosed with a first cancer between ages 34 and 44; among those initially diagnosed with one breast tumor the mutation frequency was 6.three; those diagnosed with two primary breast cancers had a mutation rate of 22 percent.

“These elevated mutation frequencies and risks for contralateral breast cancer related to these mutations underscore the need for women diagnosed with a first breast cancer at a young age regardless of family history to consider genetic testing and to discuss it with their well being care providers,” Malone stated. “If they are discovered to carry a mutation in either of the BRCA genes, they should consider strategies for treatment, prevention and heightened surveillance in relation to their increased risk of a subsequent breast cancer diagnosis.”

This international, multicenter study, which was coordinated by Memorial Sloan Kettering Cancer Center, analyzed data from 705 women with contralateral breast cancer and a comparison group of 1,398 women with unilateral breast cancer. All of the women had been first diagnosed before age 55.

Participants had been gleaned from population-based cancer registries in western Washington, Los Angeles, San Diego, Iowa and Denmark. All study participants had been tested for the presence of BRCA1 or BRCA2 mutations. None of the participants had evidence of cancer spread beyond the lymph nodes upon diagnosis.

“This is the first population-based study of these two important breast cancer susceptibility genes and their relation to contralateral breast cancer risk,” Malone stated. It is also the largest study to date of the association between BRCA mutations and contralateral breast cancer. “This study provides the clearest picture yet of the prevalence and threat of contralateral breast cancer among women inside the general population who carry mutations in BRCA1 and BRCA2.”

Previous research on these genes in relation to the danger of contralateral breast cancer has focused largely on rare, high-risk families and has been constrained by small numbers of cases.

“While contralateral breast cancer risks in our study are quite substantial, it is worth noting that they are also 10 percent to 15 percent lower overall than in past studies in high-risk settings,” Malone said. One reason for this, she said, is because this study is among the few to assess threat among substantial numbers of women without a positive family history of breast cancer.

“Getting these threat estimates right is important because of their role in clinical decision-making,” Malone said. “Our study is the first to include the full spectrum of family history profiles, from minimal to extreme danger, and thus is likely to much more accurately reflect the true threat of contralateral breast cancer among BRCA carriers inside the general population,” she stated.

More than 180,000 U.S. women are diagnosed with breast cancer annually. “With growing numbers of breast cancer survivors nationwide, the magnitude of the burden associated with the potential danger of second primary contralateral breast cancer is quite large,” Malone said.

BRCA1 and BRCA2 belong to a class of genes known as tumor suppressors. These genes help ensure genetic integrity of the cell and support prevent uncontrolled cell growth that can lead to cancer. Mutation of these genes has been linked to the development of hereditary breast and ovarian cancer.

A woman’s lifetime danger of developing breast and/or ovarian cancer is greatly increased if she inherits a mutation in either of these genes. Such a woman has an increased risk of developing breast and/or ovarian cancer at an early age (before menopause) and often has a number of close family members who have been diagnosed with these diseases.

Grants from the National Cancer Institute funded the study, which was conducted in collaboration with researchers from (in alphabetical order) City of Hope; the Danish Cancer Society; Lund University (Sweden); Memorial Sloan-Kettering Cancer Center; the University of California, Irvine; the University of Iowa; the University of Southern California; the University of Virginia; and Vanderbilt University.

At Fred Hutchinson Cancer Investigation Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for well being, knowledge and hope to their function and to the world.

Source: Fred Hutchinson Cancer Study Center

five (1 votes)

Healthcare Prof:

In a new study in mice, scientists have compensated for mutations within the Brca1 gene that can lead to cancer by deleting a second gene, which then lessens the probability of cancer. Mouse Brca1-associated mammary tumors have significant similarities to human BRCA1- associated (BReast CAncer 1, early onset) breast cancer in regard to tumor aggressiveness, high incidence, mutations and genetic instability. The study, led by scientists at National Cancer Institute (NCI), part of the National Institutes of Wellness, and their colleagues, appeared online April 1, 2010 and in print April 16, 2010, in the journal Cell.

In humans, mutations inside the BRCA1 gene increase the danger of breast, ovarian, and other cancers by impairing an important pathway for the repair of damaged DNA. Lead investigator Andre Nussenzweig, Ph.D., head of the Molecular Recombination Section of NCI’s Experimental Immunology Branch, and his colleagues found that when a gene known as 53BP1 was also defective, the formation of the mammary tumors that normally develop in Brca1 mutant mice was suppressed. Moreover, they found that inactivation of 53BP1 restored the DNA repair function that is lost when Brca1is mutated.

The protein produced by the Brca1 gene participates in an important DNA repair pathway called homologous recombination (HR). This pathway is used to repair a type of DNA damage called replication-associated chromosome breaks, which develop spontaneously when cells divide. When HR is defective, whether through Brca1 mutations or mutations in other genes whose products are involved in this pathway, cells must rely on alternative DNA repair pathways. These other pathways are much more error-prone, or mutagenic, than HR, and they can lead to the formation of abnormal and unstable chromosome structures. The resulting genomic instability increases the threat of tumor development.

Women who carry a harmful mutation in the BRCA1 gene have up to an 85 percent lifetime risk of developing breast cancer, and up to a 40 percent lifetime danger of developing ovarian cancer. To date, there are no effective or targeted therapies that overcome the breast cancer susceptibility caused by mutations in BRCA1. “Promoting HR by using drugs that inhibit toxic pathways for DNA repair could greatly reduce the development of breast and ovarian cancer in women with BRCA1 mutations,” said Nussenzweig.

The team used a strain of mice, originally developed by NIH researchers, that have a defective Brca1 gene. These mice frequently develop mammary tumors, which are similar to human breast cancers. Nussenzweig and colleagues found when the mice also had been lacking the function of a protein called 53BP1, mammary tumor formation was largely suppressed.

To investigate the molecular basis by which the loss of 53BP1 suppressed Brca1-associated mammary tumor formation, the researchers undertook a series of experiments making use of mouse cells grown in culture. These experiments showed that it was feasible to restore HR to Brca1-deficient cells by inactivation of the gene 53BP1.

Further analysis led to a model in which each Brca1 and 53BP1 are capable of binding to replication-associated chromosome breaks. According to this model, when both proteins are present, Brca1 displaces 53BP1, the HR machinery has full access towards the breaks, and HR proceeds. In Brca1-deficient cells, the binding of 53BP1 towards the site of DNA damage interferes with the activity of HR proteins. Consequently, the damage is instead repaired by an alternative mutagenic pathway that promotes cancer. When 53BP1 is absent, Brca1 is not needed to displace it. Therefore, HR can take place normally when each proteins are missing.

“Our results show that the choice of pathway used to repair DNA damage determines whether the repair is error-free or error-prone. This opens the possibility of utilizing drugs to inhibit mutagenic DNA repair pathways and promote error-free DNA repair,” said Nussenzweig.

The study also suggests that BRCA1-deficient tumors may become resistant to chemotherapy by acquiring additional mutations in certain DNA repair proteins, but that such resistance may one day be overcome by drugs developed to affect pathway choice, according the researchers.

NIH investigators from the National Heart, Lung and Blood Institute as well as the National Institute of Diabetes and Digestive and Kidney Diseases also participated inside the study, as properly as colleagues from Beckman Investigation Institute of City of Hope, Duarte, Calif.; Rockefeller University, New York City; along with the Spanish National Cancer Research Centre, Madrid, Spain.

Reference:
Nussenzweig A, et al. 53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks. Cell, April 16, 2010. DOI 10.1016/j.cell.2010.03.012.

Source
National Cancer Institute

Healthcare Prof:

5 (1 votes)

Rotterdam, The Netherlands-Screening younger women for breast cancer could make economic sense and greatly reduce wellness disparities, according to a new study conducted by researchers at the Johns Hopkins Bloomberg School of Public Health. They assessed the cost effectiveness and fairness of current breast cancer screening guidelines and located that extending screening programs to women below the age of 75 could have benefits in economic efficiency and equity. The results are published inside the April two online issue of Value in Wellness.

“Screening only older women increases unfair disparities in terms of life expectancy and quality of life,” stated Louis Niessen, MD, PhD, senior author and an associate professor with the Bloomberg School’s Department of International Wellness. “Our findings show that extending screening to younger women will lead to a better mix of well being programs and a far more balanced approach towards the fight against breast cancer. We urge for better and far more detailed assessment of breast cancer guidelines, both in the US and in Europe”

Researchers adapted an existing World Health Organization (WHO) breast cancer model to estimate cost effectiveness and equity effects of breast cancer interventions. They applied three methods to quantify the equity-efficiency trade-offs: targeting specific groups, equity weighting, and multi-criteria decision analysis and found that a comprehensive breast cancer program, including screening, for women under 75 years of age showed the most positive results within the group targeting approach and the equity weighing approach.

“In the three equity weighing approaches, targeting younger women could reduce disparities by as much as 56 percent and at $3,300 per equity quality-adjusted life year gained,” said Johns Bridges, PhD, assistant professor in the Bloomberg School’s Department of Wellness Policy and Management. “A marked reduction in disparities is likely similar in other fatal diseases with similar age distributions.”

Niessen along with colleagues from the Erasmus Medical Centre, Radboud University along with the University of East Anglia, urged policymakers and health agencies to use proper value-based weighing methods and take women’s preferences into account when next reviewing breast cancer control guidelines.

“Incorporating Equity-Efficiency Interactions in Cost-Effectiveness Analysis-Three Approaches Applied to Breast Cancer Control” was written by Stefan A. Baeten, Rob M. P. M. Baltussen, Carin A. Uyl-de Groot, John Bridges and Louis W. Niessen.

Source
ISPOR