Good morning all, As I noted in lecture on Wednesday, we remain caught-up with our lecture schedule and do not have chapter assigned for today. So, we will not meet in person for class today; instead I will offer this reading which I would like to you to consider. In our last lecture, we identified the "cell cycle" as a way to describe the normal lifespan of a cell, from its formation, through its functional life, and then its eventual end. All of our body cells are formed from mitotic cell division to begin their life, and, at the end of their functional lives, many of our cells undergo division themselves, essentially being reborn as two new daughter cells. We also identified important "checkpoints" in the cell cycle, to prevent cells from speeding through the cell cycle too rapidly. Many of our cells have functional lives of months to years, and without these checkpoints, they would otherwise just divide rapidly into new cells. As we noted, failure to stop at these cell cycle checkpoints can lead to tumors caused by uncontrolled growth; some tumors can become cancers, invading otherwise normal tissues and causing them to become cancerous as well. As you know, cancer is one of the primary causes of human mortality. We experience a variety of cancers: some are slow to progress, others very rapid; some are essentially benign while others are very deadly; some are highly invasive and others less so. The diversity if cancers we experience and the diversity of tissues that they strike represents one the of the primary difficulties in treating cancer: there is no single cure, for cancer is very diverse in its many forms. That's not to say that there aren't standardized treatments. Most hospitals have oncology boards that carefully document each occurrence of cancer, and they typically made treatment decisions based upon consultation among a team of physicians, including oncologists, radiologists, surgeons, and others. Much of their decision-making is based upon care standards that have been developed by national and international cancer agencies, such as our own American Cancer Society, which suggests treatment guidelines for the different forms of cancer. Still, we know all too well that curing cancer is difficult, and sometime impossible. The best one can hope for is to eliminate the cancerous tissue to the point at which is cannot be detected, but that is no promise that every cancerous cell has been removed, nor that it cannot re-appear. Because of the burden cancer poses to society, there are many federally-funded research groups investigating potential treatments. These include
Of course, many of the latest treatments combine multiple approaches, such as using immune cells to target delivery of cytotoxic drugs directly to cancer cells. In the news this week is report of a promising new approach to treating some kinds of cancer, based upon a metabolic starving of cancer cells. Cells that are rapidly dividing (such as those within a tumor or a cancer) are metabolically very demanding, needing large amounts of fuel. Scientists have developed methods to prevent cells from using glutamine (a glucose-like fuel source), to successfully prevent cancer growth. But, earlier formations of this treatment caused widespread side effects, because the cancer cells were not the only ones being starved of fuel. In this latest test, the scientists successfully "handcuffed" an inactive form of their drug to allow its focal delivery to cancer cells, where it was "unhandcuffed" into an active form by cancer cell enzymes. There it successfully prevented cancer growth. Even better, this new treatment actually improved immune T-cell function, providing an immunological boost to cancer elimination as well. These initial studies, done in mice, were very promising. While the road from animal studies to human uses is often long and unsure, this could mark the beginnings of a new generation of cancer treatments that are improved in their focused targeting as well as in their effectiveness at cancer elimination. https://www.sciencemag.org/news/2019/11/revamped-cancer-drug-starves-tumors-mice We'll talk more about cancer in our upcoming lectures, and I hope that this article will put some of the lecture material into practical context. Cancer touches many families, and does not discriminate by race, class, knowledge, or upbringing. May your generation be the one that finally reduces the impact that it has on our individual and our public health. Have a great weekend - see you on Monday. Sincerely, Dr. Nealen
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Good morning all, As we head into warmer weather, thoughts inevitably turn to outdoor activities. With them comes, of course, exposure to sunlight and its radiation. Natural light offers us warmth, pleasurable sensations, and stimulates vitamin D production. As we have been discussing in lab, sunlight also contains dangerous levels of UV radiation. One of the safety concepts we hear reported related to outdoor activities is the "UV index". This is a scale meant to represent the relative degree of exposure risk posed by harmful UV radiation. The World Health Organization, in partnership with other health agencies, promotes the use of this index as a way to keep the public quickly and easily informed of their exposure risk. The index is fairly easy to interpret: low index numbers, relatively low risk; higher numbers, more risk. https://www.who.int/uv/intersunprogramme/activities/uv_index/en/ Behind the index is a fair amount of science, in which measured amounts of UV exposure were assessed for their ability to cause cell and tissue damage. Many of the initial studies were done without direct knowledge of what was changing in cells, or what was driving tissue damage. Now, health scientists are able to marry environmental exposure studies to genetic studies, leading to genetic profiles for many of our genes. For example, we now know that the gene responsible for directing production of the melanocortin 1 receptor (gene MC1R) is often mutated by UV radiation; its mutation is one of the leading agents of skin cancer. The normal role of the MC1R gene product is to regulate the production of melanin (eumelanin) in our skin cells, the same melanin which gives us a 'tan' after UV exposure. We all have different levels of melanin production; those of us with lighter skin produce relatively less of it and are at higher risk of UV damage. https://ghr.nlm.nih.gov/gene/MC1R#conditions Our lab exercise of the past two weeks demonstrated how even short durations of UV exposure can mutate DNA, and also showed how critical DNA monitoring/repair is to continued health. The plate coverings that we used all provided some degree of protection from radiation. While it may be impractical to cover ourselves with tin foil when we venture outside, sunscreen or even thin cloth provided very useful protection. Remember those plates which were empty of yeast the next time you think about spending long hours in the sun - be sure to use sunscreen! Have a great weekend - Dr. Nealen Don’t Count on 23andMe to Detect Most Breast Cancer Risks, Study Warns - The New York Times4/20/2019 Good morning all, In lab recently, we have been considering some of the aspects of personalized genetics, with particular reference to genetic ancestry and the use of DNA databases in forensic and criminal investigations. During our introduction to this topic of personalized genetics, I noted that there also are significant interests in using personalized genetics as a way to assess health. Indeed, many of the commercial entities that offer to analyze an individual's DNA also offer to provide some estimate of their health risks for a variety of conditions. I also said at the time that, in our discussions, we would largely stay away from the health aspects of these services, as they are much less well-established than are the ancestry ones. I described to you recently how using DNA in criminal investigations relies upon combining two large databases (of individual genomes, and police records) to look for intersections, in order to highlight potential crime suspects or their relatives. Using DNA to assess health risks works in a very similar way, this time by evaluating databases of individual gene sequences against databases of individual health and lifestyle records. These types of tests are called genome-wide association studies (GWAS). GWAS are useful only when based upon thousands (usually, hundreds of thousands) of individuals. These are not experimental methods, so they cannot provide definitive proof of anything, but they can reveal interesting "associations" - places where genetics and health vary in consistent ways. There are lots of large databases of public health records and DNA sequences, and many researchers and even some governments are using them to investigate public health. The commercial operatives also offer to do the same for their subscribers. In the news this week is a reminder that simply claiming that such a service is available does not mean that it is a complete or accurate one. Researchers at not-for-profit health institutions are warning that those who use 23andMe health assessments of genetic risks for breast cancer (the leading type of cancer in women) are potentially being misinformed of their genetic risks. This is a big deal - many people make dramatic decisions about their health and life when learning of their genetic risks for breast cancer, such as undergoing mastectomy (breast removal). At the opposite extreme, what if a person has a substantial risk, but is told that they do not? https://www.nytimes.com/2019/04/16/health/23andme-brca-gene-testing.html The federal Food and Drug Administration (FDA) has given its approval for 23andMe (and other commercial) genetic health assessments, and this is an important reminder that FDA approval is not meant to imply that the services are the best available, more so that the services are generally safe and perhaps useful. Anyone who is using a commercial service to evaluate their genetic health risk should follow-up with their physician if they have any concerns - the better hospitals can perform some of these tests on their own. "Caveat emptor", or "buyer beware" - commercials services, by design, place emphases on their interests, first. When in doubt, a second opinion from an independent health professional is the best course of action. Have a great weekend - Dr. Nealen |
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