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The Stem Cell Theory of Cancer – Stanford Medicine Center

Posted: October 30, 2015 at 7:42 am

Research has shown that cancer cells are not all the same. Within a malignant tumor or among the circulating cancerous cells of a leukemia, there can be a variety of types of cells. The stem cell theory of cancer proposes that among all cancerous cells, a few act as stem cells that reproduce themselves and sustain the cancer, much like normal stem cells normally renew and sustain our organs and tissues. In this view, cancer cells that are not stem cells can cause problems, but they cannot sustain an attack on our bodies over the long term.

The idea that cancer is primarily driven by a smaller population of stem cells has important implications. For instance, many new anti-cancer therapies are evaluated based on their ability to shrink tumors, but if the therapies are not killing the cancer stem cells, the tumor will soon grow back (often with a vexing resistance to the previously used therapy). An analogy would be a weeding technique that is evaluated based on how low it can chop the weed stalksbut no matter how low the weeks are cut, if the roots arent taken out, the weeds will just grow back.

Another important implication is that it is the cancer stem cells that give rise to metastases (when cancer travels from one part of the body to another) and can also act as a reservoir of cancer cells that may cause a relapse after surgery, radiation or chemotherapy has eliminated all observable signs of a cancer.

One component of the cancer stem cell theory concerns how cancers arise. In order for a cell to become cancerous, it must undergo a significant number of essential changes in the DNA sequences that regulate the cell. Conventional cancer theory is that any cell in the body can undergo these changes and become a cancerous outlaw. But researchers at the Ludwig Center observe that our normal stem cells are the only cells that reproduce themselves and are therefore around long enough to accumulate all the necessary changes to produce cancer. The theory, therefore, is that cancer stem cells arise out of normal stem cells or the precursor cells that normal stem cells produce.

Thus, another important implication of the cancer stem cell theory is that cancer stem cells are closely related to normal stem cells and will share many of the behaviors and features of those normal stem cells. The other cancer cells produced by cancer stem cells should follow many of the rules observed by daughter cells in normal tissues. Some researchers say that cancerous cells are like a caricature of normal cells: they display many of the same features as normal tissues, but in a distorted way. If this is true, then we can use what we know about normal stem cells to identify and attack cancer stem cells and the malignant cells they produce. One recent success illustrating this approach is research on anti-CD47 therapy.

Next Section >> Case Study: Leukemia

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Beta cell regeneration – Center for Regenerative Medicine …

Posted: October 30, 2015 at 7:42 am

Researchers and physicians are studying how to regenerate beta cells in the lab and within the pancreas, which may lead to new treatments for type 1 and type 2 diabetes.

Beta cell dysfunction is a characteristic of both type 1 and type 2 diabetes. In type 1 diabetes, beta cells insulin-producing cells found in the pancreas are destroyed, while in type 2 diabetes, they may not produce enough insulin.

Since it's not possible today to generate new, patient-specific, functional beta cells, people with type 1 diabetes need insulin therapy. People with type 2 diabetes often need medications, with certain cases requiring insulin therapy.

Center for Regenerative Medicine researchers, led by Yasuhiro Ikeda, D.V.M., Ph.D., and Yogish C. Kudva, MBBS, both of Mayo Clinic in Rochester, Minn., are taking two related approaches to beta cell regeneration that may lead to new treatments for diabetes.

In the laboratory. In vitro beta cell regeneration uses induced pluripotent stem (iPS) cells, a type of bioengineered stem cell that acts like an embryonic stem cell. Using a person's own skin cells or blood cells as a starting point, Mayo researchers have successfully generated patient-specific iPS cells and subsequently converted them into glucose-responsive, insulin-producing cells in the laboratory.

Once fully optimized, such cells may enable a novel cell therapy for beta cell dysfunction in diabetes. And since the transplanted cells are derived from the patient's own cells, there would be no need to give the patient any immunosuppressive drugs, which are necessary for pancreas and islet cell transplants today.

In a patient's own pancreas. Mayo researchers are working to enhance a person's natural ability to regenerate beta cells using gene therapy, which involves delivering to the pancreas cellular factors known to enhance beta cell growth and regeneration.

Investigators have developed pancreatic beta cell- and exocrine tissue-specific gene delivery vectors, and they are now studying the therapeutic effects of pancreatic overexpression of beta cell regenerating factors.

Recent results have shown that pancreatic delivery of a synthesized artificial fusion protein can prevent diabetes development in drug-induced diabetic mice. Several other strategies are also being evaluated.

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American Board of Preventive Medicine – a Member Board …

Posted: October 30, 2015 at 7:41 am

Preventive Medicine is the specialty of medical practice that focuses on the health of individuals, communities, and defined populations. Its goal is to protect, promote, and maintain health and well-being and to prevent disease, disability, and death. Preventive medicine specialists have core competencies in biostatistics, epidemiology, environmental and occupational medicine, planning and evaluation of health services, management of health care organizations, research into causes of disease and injury in population groups, and the practice of prevention in clinical medicine. They apply knowledge and skills gained from the medical, social, economic, and behavioral sciences. Preventive medicine has three specialty areas with common core knowledge, skills, and competencies that emphasize different populations, environments, or practice settings: aerospace medicine, occupational medicine, and public health and general preventive medicine.

Aerospace medicine focuses on the clinical care, research, and operational support of the health, safety, and performance of crewmembers and passengers of air and space vehicles, together with the support personnel who assist operation of such vehicles. This population often works and lives in remote, isolated, extreme, or enclosed environments under conditions of physical and psychological stress. Practitioners strive for an optimal human-machine match in occupational settings rich with environmental hazards and engineering countermeasures.

Occupational medicine focuses on the health of workers, including the ability to perform work; the physical, chemical, biological, and social environments of the workplace; and the health outcomes of environmental exposures. Practitioners in this field address the promotion of health in the work place, and the prevention and management of occupational and environmental injury, illness, and disability.

Public health and general preventive medicine focuses on promoting health, preventing disease, and managing the health of communities and defined populations. These practitioners combine population-based public health skills with knowledge of primary, secondary, and tertiary prevention-oriented clinical practice in a wide variety of settings.

The purpose of the American Board of Preventive Medicine is::

The American Board of Preventive Medicine, Incorporated (ABPM) is a member board of the American Board of Medical Specialties. ABPM originated from recommendations of a joint committee comprised of representatives from the Section of Preventive and Industrial Medicine and Public Health of the American Medical Association and the Committee on Professional Education of the American Public Health Association. The Board was incorporated under the laws of the State of Delaware on June 29, 1948 as "The American Board of Preventive Medicine and Public Health, Incorporated."

In 1952 the name was changed to The American Board of Preventive Medicine, Incorporated. In February 1953 the Advisory Board of Medical Specialties and the Council on Medical Education and Hospitals of the American Medical Association authorized certification by the Board of preventive medicine specialists in Aviation Medicine (the name was changed to Aerospace Medicine in 1963); in June 1955, preventive medicine specialists in Occupational Medicine; in November 1960, preventive medicine specialists in General Preventive Medicine; and in 1983, Public Health and General Preventive Medicine were combined into one specialty area of certification. In 1989 the American Board of Preventive Medicine was approved to offer a subspecialty certificate in Undersea Medicine (the name was changed to Undersea and Hyperbaric Medicine in 1999), in 1992 a subspecialty certificate in Medical Toxicology, and in 2010 a subspecialty certificate in Clinical Informatics.

The Board is a non-profit corporation, and no member (officer or director) may receive any salary or compensation for services. The Board consists of members nominated by the organizations listed below:

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Cell Therapy and Regenerative Medicine

Posted: October 29, 2015 at 2:41 pm

Adult (Somatic) stem cells are unspecialized cells that are found in different parts of the body and, depending on the source tissue, have different properties. Adult stem cells are capable of self-renewal and give rise to daughter cells that are specialized to form the cell types found in the original body part.

Adult stem cells are multipotent, meaning that they appear to be limited in the cell types that they can produce based on current evidence. However, recent scientific studies suggest that adult stem cells may have more plasticity than originally thought. Stem cell plasticity is the ability of a stem cell from one tissue to generate the specialized cell type(s) of another tissue. For example, bone marrow stromal cells are known to give rise to bone cells, cartilage cells, fat cells and other types of connective tissue (which is expected), but they may also differentiate into cardiac muscle cells and skeletal muscle cells (this was not initially thought possible).

Hematopoietic stem cells that give rise to all blood and immune cells are today the most understood of the adult stem cells. Hematopoietic stem cells from bone marrow have been providing lifesaving cures for leukemia and other blood disorders for over 40 years. Hematopoietic stem cells are primarily found in the bone marrow but have also been found in the peripheral blood in very low numbers. Compared to adult stem cells from other tissues, hematopoietic stem cells are relatively easy to obtain.

Mesenchymal stem cells are also found in the bone marrow. Mesenchymal stem cells are a mixed population of cells that can form fat cells, bone, cartilage and ligaments, muscle cells, skin cells and nerve cells.

Hematopoietic and stromal stem cell differentiation:4

Umbilical cord blood from newborns is a rich source of hematopoietic stem cells. Research has found that these stem cells are less mature than other adult stem cells, meaning that they are able to proliferate longer in culture and may contribute to a broader range of tissues. Research is ongoing to determine whether umbilical cord stem cells are pluripotent or multipotent and the extent of their plasticity.

Cord blood, which traditionally has been discarded, has emerged as an alternative source of hematopoietic stem cells for the treatment of leukemia, lymphoma and other lethal blood disorders. It has also been used as a life-saving treatment for children with infantile Krabbes disease, a lysosomal storage disease that produces progressive neurological deterioration and death in early childhood.

Regardless of the adult stem cells' source bone marrow, umbilical cord blood or other tissues these cells are present in minute quantities. This makes identification, isolation and purification challenging. Scientists are currently trying to determine how many kinds of adult stem cells exist and where they are located in the body.

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Hormone replacement therapy (male-to-female) – Wikipedia …

Posted: October 29, 2015 at 1:43 am

Hormone replacement therapy of the male-to-female type (MTF HRT) is a type of hormone replacement therapy for transgender and transsexual people. It changes the balance of sex hormones in the body. Some intersex people also receive HRT, either starting in childhood to confirm the assigned sex, or later, if this assignment has proven to be incorrect.

Its purpose is to cause the development of the secondary sex characteristics of the desired sex. It cannot undo many of the changes produced by the first natural occurring puberty, which may necessitate surgery and/or epilation (see below).

The requirements for hormone replacement therapy vary immensely, often psychological counseling is required.

Under WPATH guidelines the Mental Health Provider requires individuals to satisfy two sets of criteria eligibility and readiness to undertake any stage of transition including hormone replacement therapy. Eligibility involves the patient meeting requirements from a major diagnostic tool, such as the ICD-10, DSM-IV-R or the DSM-V. ICD-10 requirements are for either Transsexualism or Gender identity disorder of childhood.[1]

The ICD-10 criteria for Transsexualism include the individual having a transsexual identity of over 2 years, a strong and persistent desire to live as a member of the opposite sex, usually accompanied by the desire to make their body as congruent as possible with the preferred sex through surgery and hormone treatments. These individuals cannot be diagnosed with Transsexualism if it is believed to be a result of another mental disorder, or a genetic, intersex or chromosomal abnormality.

The ICD-10 criteria for Gender identity disorder of childhood in males include the individual being pre-pubescent and having intense and persistent distress about being a boy. The distress must be present for at least six months. The child must either:

The DSM-IV-R criteria for Gender Identity Disorder includes four main criteria. The DSM-IV-R also requests that the individual's sexuality is noted.

In children this may be demonstrated by them meeting four or more of the following criteria:

Adolescents and Adults must display a persistent desire to be the other sex, frequent passing as the other sex, desire to live or be treated as the other sex, or the conviction that they have the typical feelings and reactions of the other sex.

In boys this may manifest as an assertion that their penis or testes are disgusting or will disappear, or asserting that it is better not to have a penis.

In adults and adolescents this manifests as a preoccupation with removing primary or secondary sex characteristics, such as a demand for surgery or hormone replacement therapy.

The DSM-V moves from Gender Identity Disorder to Gender Dysphoria to avoid the implication that gender nonconformity is in itself a mental disorder, but a similar entry remains in the DSM-V so that individuals may still seek treatment.[2] The DSM-V, unlike the DSM-IV and ICD-10, separates Gender Dysphoria from sexual paraphilias, and diagnoses on the basis of a strong desire that one has feelings and convictions typical of the other sex, or that one strongly desires to be treated as the other sex or be rid of one's sex characteristics.

The readability of patients to transition is also relevant to undertake hormone replacement therapy, which includes the patient's likelihood to take hormones in a responsible manner, have made progress in mastering other identified problems that leads to improving or continuing stable mental health, and have had further consolidation of gender identity during psychotherapy or Real Life Experience of their desired gender role.[3]

Some organizations still require a period of time living as the desired gender role, based on standards such as the Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People (WPATH). This period is sometimes called the Real Life Experience (RLE). The Endocrine Society in 2009 specified that individuals should either have a documented 3 months Real Life Experience or a period of psychotherapy of length specified by the mental health provider, usually a minimum of 3 months.[3]

Some people, especially individuals from the transgender community, say that RLE is psychologically harmful and is a form of "gatekeeping" effectively barring people from transitioning for as long as possible, if not permanently.[who?]

Some individuals choose to self-administer their medication ("do-it-yourself"), often because available doctors have too little experience in this matter, or no doctor is available in the first place. Sometimes, trans persons choose to self-administer because their doctor will not prescribe hormones without a letter from the patient's therapist stating that the patient meets the diagnostic criteria for GID and is making an informed decision to transition. Many therapists require at least three months of continuous psychotherapy and/or a real life test in order to write such a letter as is suggested in the HBIGDA Standards of Care. As many individuals must pay for evaluation and care out-of-pocket, expense can also be prohibitive to pursuing such therapy.

However, self-administration of certain medications (namely ethinyl estradiol) and antiandrogens (namely spironolactone, cyproterone acetate, flutamide, and nilutamide) is potentially dangerous and can cause an elevation in liver enzymes or other potentially dangerous adverse effects.[4]

For trans women, taking estrogens causes, among other changes:

For male-to-female transgender people, HRT often includes antiandrogens in addition to the estrogens and progestogens mentioned above.

HRT does not usually cause facial hair growth to be impeded or the voice to change.

The psychological changes are harder to define, because HRT is usually the first physical action that takes place when transitioning and the act itself of beginning HRT has a significant psychological effect, which is difficult to distinguish from hormonally induced changes.

However, a problem may arise with the structure of hip bones, since cisgender women generally have larger hip bones to accommodate pregnancy.

During HRT, especially in the early stages of treatment, blood work should be consistently done to assess hormone levels and liver function. It is suggested by Endocrine Society that individuals have blood tests every 3 months in the first year of hormone replacement therapy for estradiol and testosterone and monitor spironolactone, if used, every 23 months in the first year.[3]

The optimal ranges listed for estrogen only apply to individuals taking bioidentical hormones (i.e., estradiol, including esters) and do not apply to those taking synthetic or other non-bioidentical preparations (e.g., ethinyl estradiol or conjugated equine estrogens (Premarin)). While the ranges given are optimal, the Endocrine Society further state that estrogen levels of 200pg/ml ought not to be exceeded.[80]

There should also be medical monitoring, including complete blood counts, renal and liver function, lipid and glucose metabolism, as well as monitoring prolactin levels, body weight and blood pressure.[81]

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Insights From Identical Twins

Posted: October 29, 2015 at 1:43 am

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Epigenetics

Insights From Identical Twins

Because identical twins develop from a single fertilized egg, they have the same genome. So any differences between twins are due to their environments, not genetics. Recent studies have shown that many environmentally induced differences are reflected in the epigenome.

Chromosome 3 pairs in each set of twins are digitally superimposed. One twin's epigenetic tags are dyed red and the other twin's tags are dyed green. When red and green overlap, that region shows up as yellow. The 50-year old twins have more epigenetic tags in different places than do 3-year-old twins.

The insight we gain from studying twins helps us to better understand how nature and nurture work together. For well over a century, researchers have compared characteristics in twins in an effort to determine the extent to which certain traits are inherited, like eye color, and which traits are learned from the environment, such as language. Typically taking place in the field of Behavioral Genetics, classical twin studies have identified a number of behavioral traits and diseases that are likely to have a genetic component, and others that are more strongly influenced by the environment.

Depending on the study and the particular trait of interest, data is collected and compared from identical or fraternal twins who have been raised together or apart. Finding similarities and differences between these sets of twins is the start to determining the degree to which nature and environment play a role in the trait of interest.

Twin studies have identified some traits that have a strong genetic component, including reading disabilities like dyslexia. Other traits, like arthritis, are more likely influenced by the environment.

Twins share the same genes but their environments become more different as they age. This unique aspect of twins makes them an excellent model for understanding how genes and the environment contribute to certain traits, especially complex behaviors and diseases.

For example, when just one twin gets a disease, researchers can look for elements in the twins' environments that are different. Or when both twins get a disease, researchers can look for genetic elements shared among similar twin pairs. These types of data are especially powerful when collected from large numbers of twins. Such studies can help pinpoint the molecular mechanism of a disease and determine the extent of environmental influence, potentially leading to the prevention and treatment of complex diseases.

To illustrate, for twins with schizophrenia, 50% identical twins share the disease, while only about 10-15% of fraternal twins do. This difference is evidence for a strong genetic component in susceptibility to schizophrenia. However, the fact that both identical twins in a pair don't develop the disease 100% of the time indicates that other factors are involved.

Identical twins (left) share all their genes and their home environment. Fraternal twins (right) also share their home environment, but only half of their genes. So a greater similarity between identical twins for a particular trait compared to fraternal twins provides evidence that genetic factors play a role.

Comparing Identical and Fraternal Twins: A higher percentage of disease incidence in both identical twins is the first indication of a genetic component. Percentages lower than 100% in identical twins indicates that DNA alone does not determine susceptibility to disease.

Wong A.H., Gottesman I., Petronis A. (2005) Phenotypic differences in genetically identical organisms: the epigenetic perspective. Human Molecular Genetics, 14: Review Issue 1, R11-R18.

Fraga, M.F. et al. (2005) Epigenetic differences arise during the lifetime of monozygotic twins. PNAS, 102:10604-9.

Poulsen P., Esteller M., Vaag A., Fraga M.F. (2007) The Epigenetic Basis of Twin Discordance in Age-Related Diseases. Pediatric Research, 61: 38R-42R (subscription required).

APA format: Genetic Science Learning Center (2014, June 22) Insights From Identical Twins. Learn.Genetics. Retrieved October 29, 2015, from http://learn.genetics.utah.edu/content/epigenetics/twins/ MLA format: Genetic Science Learning Center. "Insights From Identical Twins." Learn.Genetics 29 October 2015 <http://learn.genetics.utah.edu/content/epigenetics/twins/> Chicago format: Genetic Science Learning Center, "Insights From Identical Twins," Learn.Genetics, 22 June 2014, <http://learn.genetics.utah.edu/content/epigenetics/twins/> (29 October 2015)

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Human genetics – Wikipedia, the free encyclopedia

Posted: October 29, 2015 at 1:42 am

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Gene therapy – Wikipedia, the free encyclopedia

Posted: October 28, 2015 at 12:42 pm

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Transhuman – Wikipedia, the free encyclopedia

Posted: October 27, 2015 at 5:42 pm

Transhuman or trans-human is the concept of an intermediary form between human and posthuman.[1] In other words, a transhuman is a being that resembles a human in most respects but who has powers and abilities beyond those of standard humans.[2] These abilities might include improved intelligence, awareness, strength, or durability. Transhumans sometimes appear in science-fiction as cyborgs or genetically-enhanced humans.

The use of the term "transhuman" goes back to French philosopher Pierre Teilhard de Chardin, who wrote in his 1949 book The Future of Mankind:

Liberty: that is to say, the chance offered to every man (by removing obstacles and placing the appropriate means at his disposal) of 'trans-humanizing' himself by developing his potentialities to the fullest extent.[3]

And in a 1951 unpublished revision of the same book:

In consequence one is the less disposed to reject as unscientific the idea that the critical point of planetary Reflection, the fruit of socialization, far from being a mere spark in the darkness, represents our passage, by Translation or dematerialization, to another sphere of the Universe: not an ending of the ultra-human but its accession to some sort of trans-humanity at the ultimate heart of things.[4]

In 1957 book New Bottles for New Wine, English evolutionary biologist Julian Huxley wrote:

The human species can, if it wishes, transcend itself not just sporadically, an individual here in one way, an individual there in another way, but in its entirety, as humanity. We need a name for this new belief. Perhaps transhumanism will serve: man remaining man, but transcending himself, by realizing new possibilities of and for his human nature. "I believe in transhumanism": once there are enough people who can truly say that, the human species will be on the threshold of a new kind of existence, as different from ours as ours is from that of Peking man. It will at last be consciously fulfilling its real destiny.[5]

One of the first professors of futurology, FM-2030, who taught "new concepts of the Human" at The New School of New York City in the 1960s, used "transhuman" as shorthand for "transitional human". Calling transhumans the "earliest manifestation of new evolutionary beings", FM argued that signs of transhumans included physical and mental augmentations including prostheses, reconstructive surgery, intensive use of telecommunications, a cosmopolitan outlook and a globetrotting lifestyle, androgyny, mediated reproduction (such as in vitro fertilisation), absence of religious beliefs, and a rejection of traditional family values.[6]

FM-2030 used the concept of transhuman as an evolutionary transition, outside the confines of academia, in his contributing final chapter to the 1972 anthology Woman, Year 2000.[7] In the same year, American cryonics pioneer Robert Ettinger contributed to conceptualization of "transhumanity" in his book Man into Superman.[8] In 1982, American Natasha Vita-More authored a statement titled Transhumanist Arts Statement and outlined what she perceived as an emerging transhuman culture.[9]

Jacques Attali, writing in 2006, envisaged transhumans as an altruistic vanguard of the later 21st century:

Vanguard players (I shall call them transhumans) will run (they are already running) relational enterprises in which profit will be no more than a hindrance, not a final goal. Each of these transhumans will be altruistic, a citizen of the planet, at once nomadic and sedentary, his neighbor's equal in rights and obligations, hospitable and respectful of the world. Together, transhumans will give birth to planetary institutions and change the course of industrial enterprises.[10]

In March 2007, American physicist Gregory Cochran and paleoanthropologist John Hawks published a study, alongside other recent research on which it builds, which amounts to a radical reappraisal of traditional views, which tended to assume that humans have reached an evolutionary endpoint. Physical anthropologist Jeffrey McKee argued the new findings of accelerated evolution bear out predictions he made in a 2000 book The Riddled Chain. Based on computer models, he argued that evolution should speed up as a population grows because population growth creates more opportunities for new mutations; and the expanded population occupies new environmental niches, which would drive evolution in new directions. Whatever the implications of the recent findings, McKee concludes that they highlight a ubiquitous point about evolution: "every species is a transitional species".[11]

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Transhumanism Wikipedia

Posted: October 27, 2015 at 5:42 pm

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