Par-4 gene kills cancer cells:
LEXINGTON, Ky. (November 27, 2007) − A mouse resistant to cancer, even highly-aggressive types, has been created by researchers at the University of Kentucky. The breakthrough stems from a discovery by UK College of Medicine professor of radiation medicine Vivek Rangnekar and a team of researchers who found a tumor-suppressor gene called "Par-4" in the prostate.
The researchers discovered that the Par-4 gene kills cancer cells, but not normal cells. There are very few molecules that specifically fight against cancer cells, giving it a potentially therapeutic application.
Funded by several grants from the National Institutes of Health, Rangnekar's study is unique in that mice born with this gene are not developing tumors. The mice grow normally and have no defects. In fact, the mice possessing Par-4 actually live a few months longer than the control animals, indicating that they have no toxic side effects.
"We originally discovered Par-4 in the prostate, but it's not limited to the prostate. The gene is expressed in every cell type that we've looked at and it induces the death of a broad range of cancer cells, including of course, cancer cells in the prostate," said Rangnekar. "The interesting part of this study is that this killer gene is selective for killing cancer cells. It will not kill normal cells and there are very, very few selective molecules out there like this."
To further investigate the potential therapeutic benefits of this gene, Rangnekar's team introduced it into the egg of a mouse. That egg was then planted into a surrogate mother.
"The mouse itself does not express a large number of copies of this gene, but the pups do and then their pups start expressing the gene," Rangnekar said. "So, we've been able to transfer this activity to generations in the mouse."
The implications for humans could be that through bone marrow transplantation, the Par-4 molecule could potentially be used to fight cancer cells in patients without the toxic and damaging side effects of chemotherapy and radiation therapy.
"When a cancer patient goes to the clinic, they undergo chemotherapy or radiation and there are potential side effects associated with these treatments," Rangnekar said. "We got interested in looking for a molecule which will kill cancer cells and not kill normal cells, but also would not be toxic with regard to the production of side effects to the entire organism. We are thinking of this in a holistic approach that not only would get rid of the tumor, but also not harm the organism as a whole. Before this animal study, we published a lot of work indicating that in cell culture, there's no killing of normal cells. This is the proof that it doesn’t kill normal cells because the mouse is alive and healthy."
Rangnekar admits there is much more work to be done before this research can be applied to humans, but agrees that is the most logical next step.
"I look at this research from the standpoint of how it can be developed to the benefit of the cancer patient and that's really what keeps us focused all this time," said Rangnekar. "If you look at the pain that cancer patients go through, not just from the disease, but also from the treatment – it's excruciating. If you have someone in your family, like I did, who has gone through that, you know you can see that pain. If you can not only treat the cancer, but also not harm the patient, that's a major breakthrough. That's happening with these animals and I think that's wonderful."
... is embodied in Dexcom, Inc.'s homerun:
"It's absolutely changed my life and my outlook," said Joel Mason, who's been living with Type 2 diabetes for seven years. "For the first time in a long time, I have greater peace of mind."
About three months ago Mason was fitted with a continuous glucose monitoring system. A glucose sensor is placed under the skin and information is sent to a wireless electronic receiver worn like a pager. It monitors glucose levels every five minutes and can send off a signal when sugar levels get too high or too low.
"Instead of waiting to see what my reaction is, I can act," Mason said.
The continuous monitor not only provides frequent and convenient glucose readings, it enables the user to consider trends in addition to absolute glucose levels. In addition, the new sensors give previously unavailable information - glucose readings between episodic finger stick values. To some the knownledge will be revolutionary and enable better lifestyle and treatment choices.
However, as with all new technology, continuous monitoring is not for everyone. The devices require what some may consider an arduous calibration procedure which involves multiple finger sticks. And, not every sensor insertion will be successful. Add to this the fact that the FDA has approved continous monitoring for adjunctive use (i.e., take a fingerstick before any treatment decision) and many will be reluctant to spend their savings for extra information insurance companies may not cover.
In my opinion, despite these imperfections, continuous monitors will revolutionize diabetes treatment and early adopters are likely to benefit later in life by reducing the likelihood of significant health complications related to diabetes.
In 2005 a study was done among several thousand healthy young men, members of the Israeli Defense Forces. Their blood sugar was measured using a test called fasting blood glucose, and then the men were followed for nearly six years to see who developed diabetes. Men with a level between 95 and 99 ml/dl were almost three times as likely to get diabetes as were men with levels between 50 and 81. Men with levels around 90 had nearly twice the risk. What's particularly striking is that the standard definition of normal levels has been 100 or less. Yet there is clear evidence that risk starts going up even before 100.
A new model for calculating invasive breast cancer risk, called the CARE model, has been found to give better estimates of the number of breast cancers that would develop in African American women 50 to 79 years of age than an earlier model which was based primarily on data from white women. Both models were designed to be used by health care professionals and should either be used by them or in consultation with them. Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and their collaborators report on the study methodology and results online in JNCI on November 27, 2007.
"NCI's Breast Cancer Risk Assessment Tool has been widely used for counseling women and determining eligibility for breast cancer prevention trials," said NCI Director John E. Niederhuber, M.D. "The development of the CARE model highlights the need to develop targeted tools to assess an individual woman's risk, and those tools must be based on many factors that also assure that the tool can be used in a non-discriminatory manner."
The NCI investigators worked with colleagues from the Women's Contraceptive and Reproductive Experiences (CARE) Study, the Women's Health Initiative, and the Study of Tamoxifen and Raloxifene trial (a breast cancer prevention trial) to produce and test the new model. Some members of the team had worked on both the CARE and earlier model, called BCRAT (Breast Cancer Risk Assessment Tool). Because of the higher accuracy of the CARE model for African American women, the NCI authors are now recommending its use for counseling these women regarding their risk of breast cancer.
While the BCRAT allows for projections for African American women and for women from other racial and ethnic groups, these projections are based on certain assumptions. In particular, it is assumed that the relative risk of breast cancer associated with having a specific profile of risk factors for white women applies to African American women and to women from other racial and ethnic groups as well. Because of the need to rely on these various assumptions, rather than on sufficient data from African American women and women in other racial and ethnic groups, BCRAT, which can be found on the NCI Web site at http://www.cancer.gov/bcrisktool, includes a disclaimer for African American women and for women in other groups that their projections might be inaccurate.
To develop a new model that would more accurately assess an African American woman's chance of developing breast cancer, researchers in the CARE study examined data from 1,607 African American women with invasive breast cancer and 1,637 African American women of similar ages who did not have breast cancer. The factors used in the model were age at first menstrual period, number of first degree relatives (mother or sisters) who had breast cancer, and number of previous benign breast biopsy examinations. A woman's age at the birth of her first child, a risk factor for white women, did not improve prediction in African American women and so was not included in the model. Risk was calculated by combining information on these factors with African American rates of new invasive breast cancer from NCI's Surveillance, Epidemiology and End Results Program and with national mortality data.
To test the accuracy of the model, researchers compared data in the CARE model with data from the 14,059 African American women aged 50 to 79 in the Women's Health Initiative (WHI) study who had no prior history of breast cancer. From the risk factor profiles for breast cancer that were collected at entry into the WHI, the researchers used the CARE model to estimate the number of women who would be expected to develop invasive breast cancer and found that the model predicted that 323 would be affected, close to the 350 breast cancers in African American women that actually occurred during the WHI follow up. According to Mitchell H. Gail, M.D., NCI, the lead author of this study, "The CARE model predicted the numbers of breast cancer diagnoses well overall, and in most categories."
One of the key uses of the BCRAT has been to determine eligibility criteria for a number of breast cancer prevention trials. For African American women 45 and older, the CARE model risk projections were usually higher than those from the BCRAT. To assess what the impact of using the CARE model might have been on a recently completed prevention trial, the researchers used eligibility screening data from 20,278 African American women who were examined in the Study of Tamoxifen and Raloxifene (STAR) trial between 1999 and 2004. The investigators estimated that 30.3 percent of African American women would have had significant five-year invasive breast cancer risks based on the CARE model, compared to only 14.5 percent based on BCRAT.
"African American women were both more interested in and more likely to enroll in the STAR trial compared to the earlier Breast Cancer Prevention Trial, but the recruitment process and our enrollment task would have been easier if the CARE model had been available," said Worta McCaskill-Stevens, M.D., NCI, one of the leaders of the STAR trial.
Additionally, inaccurate projections using the BCRAT could result in African American women receiving an underestimate of their breast cancer risk. As a result of this underestimate, African American women might not get counseling about actions they could take to reduce their risk. "There has been great interest in developing race- or ethnicity-specific adaptations of the BCRAT model that are based on sufficient race- or ethnicity-specific data, and the CARE data enabled us to develop the new model," said Gail.
It should be noted that the CARE model, like the BCRAT, needs to be approached with caution or avoided for certain special populations. These models should not be used for women with a previous history of breast cancer. The models tend to underestimate risk in women who have received radiation to the chest and in women who are known to carry mutations associated with increased risk of breast cancer, such as mutations in the BRCA1 and BRCA2 genes. While the CARE model has not yet been incorporated into the BCRAT on the NCI Web site, NCI plans to have the tool updated by the spring of 2008.
FDA's Center for Devices and Radiological Health conducted a survey of outside experts to identify major anticipated trends in medical device technologies over the next ten years. This analysis was undertaken to identify areas in which new or significantly increased product development activity is likely. The fifteen participants included physicians, engineers, healthcare policymakers and payers, manufacturers, futurists and technology analysts.
The process began with a questionnaire modelled on conventional Delphi techniques, in which participants assigned numerical scores to 21 medical technology areas reflecting their expectations regarding (A) probability of new product development, (B) likely patient population size, (C) potential benefits, (D) potential risks, and (E) overall importance of the technology area for medical device evolution over the decade. To complement the Delphi approach, each participant was later individually interviewed in a partially-structured format. Finally, participants were invited to an interactive one-day workshop to promote a synergistic interplay of viewpoints.
The questionnaire and interview results yielded a consensus that 18 of the technologies were expected to be important, and identified many specific examples of product types representing these technologies. Workshop discussions and subsequent CDRH analysis revealed that nearly all of the technologies and product types resulted from six major trends in (1) computer-related technologies, (2) molecular medicine, (3) home- and self-care, (4) minimally invasive procedures, (5) device/drug hybrid products, and (6) organ replacement/assist devices using hardware and tissue-engineered components.
In addition to the six major trends, participants noted a number of other patterns and issues having potential significance for medical device evolution including cost-containment pressures, technologically-tailored product customization, prevention-oriented health care, 'medicalization' of traditionally 'normal' conditions, interest in medical 'enhancement', special-interest patient advocacy groups, baby-boomers' activist patient attitudes and growing geriatric populations.
The workshop dialogue underscored the complex interactions between four groups who play critical roles in the emergence of new medical devices: investors and manufacturers, physicians and other direct health care providers, institutional payers and reimbursers, and patients and consumers.
A brainstorming session revealed four types of 'wild-card' developments which could induce major disruptions into the projected trends: radical scientific breakthroughs (e.g., in aging research); dramatic decreases in resources for health care research or delivery (e.g., from a global depression); major new public health problems (e.g., a substantial epidemic); and basic changes in societal values (e.g., eradication of health care disparities).
Source: FDA