History of Breast Cancer Identification and Treatment

History of Breast Cancer Identification and Treatment A City of Strings In the late 1970s, researchers at Standford and UCSF had invented a technology known as recombinant DNA. They founded a biotech company called Genentech in 1976 to leverage on this technology to develop new drugs. Genentech used Recombinant DNA technology to synthesize human proteins in bacteria cells instead of extracting proteins from animal and human organs. From 1982 to 1985, Genentech had manufactured many important drugs such as human insulin, a clotting factor to treat hemophilia, and a human growth hormone all engineered and produced in bacterial cells. In 1984, a team of researchers led by a German scientist named Axel Ullrich from Genentech discovered the human homolog of the neu gene, an oncogene previously discovered by Weinberg. In the summer of 1986, Ullrich told the story of the isolation of Her-2 at a UCLA seminar. Among the audience was a UCLA oncologist named Dennis Slamon. Slamon had a collection of cancer tissues from patients at UCLA. He proposed a simple collaboration to Ullrich. If Ullrich sent him the Her-2 DNA probes, Slamon could test his collection for cancer cells with hyperactive Her-2 genes. Ullrich agreed. Slamon tested Her-2 with his collection of cancer cells. He discovered that breast cancers could be divided into two types: Her-2 positive and Her-2 negative, depending on whether or not the cancer cells amplify Her-2 by making multiple copies. Her-2 positive tumors are more aggressive, more metastatic, and more likely to kill than Her-2 negative tumors. The association of Her-2 with an aggressive breast cancer prompted Ullrich to look for a drug to shut off the Her-2 function. In 1988, Genentech produced a mouse antibody that could inactivated Her-2 and sent it to Slamon. Slamon tested the antibody with cancer cells in a dish, the cancer cells stopped growing and died. When he injected the antibody into mice with Her-2 positive tumors, the tumors also disappeared. He concluded that the Her-2 inhibition worked in an animal model. Both Slamon and Ullrich expected Genentech to leap at the opportunity. But Genentech got cold feet and wanted to focus on simpler and more profitable drugs. Feeling dejected, Ullrich left Genentech, leaving Slamon alone at UCLA trying to keep the Her-2 project alive at Genentech. Eventually, Slamon and Art Levinson, a molecular biologist at Genentech, convinced a tiny entrepreneurial team to push ahead with the Her-2 project. In the summer of 1990, Genentech produced a human Her-2 antibody ready for clinical trials. They called it Herceptin. Fifteen women enrolled in Slamons trial at UCLA in 1992. The drug was combined with a standard chemotherapy drug, both delivered intravenously. Only five of the original cohort continued the trial to its six-month end point. One of them is Barbara Bradfield. She had told Slamon that she was at the end of the road and had accepted what seemed inevitable, when Slamon tried to enroll her in the trial in the summer of 1991. She survives today. Drugs, Bodies, and Proof By the summer of 1993, news of the Herceptin early phase trial had spread through the community. Her-2 positive breast cancer is one of the most fatal variants of the disease, and patients will try any therapy that could produce a positive response. Cancer activist urged the release of the drug to patients who had failed other therapies. These patients, they argued, could not wait for the drug to undergo the long periods of clinical trial; they wanted a life saving medicine now. For Genentech, Herceptin had not been approved by the FDA. Genentech wanted carefully executed early phase trials. Marti Nelson, a gynecologist in California, had breast cancer when she was 33 in 1987. In 1993, six years after her initial surgery, her cancer had relapsed. She wanted to test the tumor for Her-2 sensitivity, but her HMO insisted that the test was useless because Herceptin was in investigational trials. In the summer of 1993, she contacted the Breast Cancer Action (BCA) project for help. Working through its activist networks, BCA asked several laboratories to test Nelsons tumor. In October 1994, the tumor was found to be Her-2 positive. She would be an ideal candidate for the drug. But the news came too late. She died nine days later. On December 4, 1994, a group of women from the BCA staged a funeral procession for Nelson through the Genentech campus. Unable to silence the activists, Genentech joined them. In 1995, Genentech agreed to provide an expanded access program for Herceptin, allowing oncologist to treat patients outside clinical trials. Trial Results On May 17, 1998, Slamon reported the results of the clinical trial at the 34th meetings of the American Society of Clinical Oncology in Los Angeles. In the pivotal 648 study, 469 women had received standard chemotherapy and were randomized to receive either Herceptin or a placebo. Women treated with Herceptin had shown a clear a measurable benefit. Response rates had increased by 150 percent, shrinking more tumors, and extending lives by four to five months compared to the control arm. In 2003, two studies were launched to test Herceptin in early stage breast cancer. When the trials were combined, overall survival in women treated with Herceptin was increased by 33 percent. A Four-Minute Mile In 1973, Janet Rowley identified a unique chromosomal aberration in chronic myeloid leukemia (CML) cells. The abnormality, the so-called Philadelphia chromosome, resulted from a translocation in which the head of chromosome 22 and the tail of chromosome 9 had been fused to create a new gene. A team of Dutch researchers isolated the gene on Chromosome 9 in 1982. They called it abl. And in 1984, they isolated abls partner on chromosome 22 a gene called Bcr. In normal cells, Bcr and abl are separate genes living on separate chromosomes. But in CML cells, the fusion of the two genes created a new chimera called Bcr-abl which coded a hyperactive kinase that causes cells to divide without control. In the mid-1980s, a team of chemists at Ciba-Geigy was trying to develop selective kinase inhibitors. Ciba-Geigy was a pharmaceutical company in Basel, Switzerland.ÂÂ   The team was headed by a Swiss physician named Alex Matter, and an English biochemist named Nick Lydon. In 1986, Matter and Lydon discovered a simple skeletal chemical that could bind a kinase and inhibit its function. By the early 1990s. Matter and Lydon had created dozens of new molecules with similar structures. When Lydon tested these molecules on various kinases, he discovered that they were kinase inhibitors with extraordinary specificity. What Matter and Lydon needed now was a disease in which to apply this collection of chemicals. In the late 1980s, Nick Lydon met Brian Druker at the Dana-Farber Cancer Institute. Druker, a young faculty member at the institute, was interested in CML the cancer driven by the Bcr-abl kinase. He proposed an ambitious collaboration effort to test the kinase inhibitors on the patients at the institute. But the project was tabled because the lawyers could not agree to terms. In 1993, Druker reconnected with Lydon after he left Boston to start his own laboratory in Portland at the Oregon Health and Science University (OHSU). Lydon informed Druker that the Ciba-Geigy team had found a molecule called CGP57148 that might inhibit Bcr-abl with high specificity. Revealing little about the potentials of the chemicals, Druker got a collaboration agreement signed between OHSU and Ciba-Geigy. In the summer of 1993, Druker added the drug from Lydon to CML cells in a petri dish. Overnight, the CML cells were dead. He induced CML tumors into mice and then treated the mice with the drug. The tumors regressed in days, leaving behind the normal blood cells. He drew out samples of bone marrow from a few patients with CML and applied the drug to the cells in a petri dish. The leukemia cells in the marrow died immediately, leaving behind the normal blood cells. He had cured leukemia in the dish. Druker expected Ciba-Geigy to be excited about these results. But in Basel, Ciba-Geigy has just merged with its arch rival into a pharmaceutical behemoth called Novartis. The prospect of spending millions on a drug to benefit thousands gave Novartis cold feet. Novartis finally relented in early 1998. They changed the name of the drug to Gleevec. In the initial phase of the study, 53 out of 54 patients receiving the drug showed a complete response within days. The remissions extended into weeks and months as the patients continued the medicine. The initial phase of the trial was a success. The Red Queens Race In the fifth year of their Gleevec trial, Charles Sawyer and Mashe Talpaz found the vast proportion of CML patients maintained deep remissions on the drug. But occasionally, a patients leukemia became Gleevec-resistant and stopped responding to Gleevec. Sawyers discovered that the CML cells become Gleevec-resistant by altering the structure of the molecule. In 2005, Sawyerss team generated another kinase inhibitor, called dasatinib, to target Gleevec-resistant Bcr-abl. The effect of this new drug on Gleevec-resistant patients was remarkable: the leukemia cells disappeared again. Even targeted therapy was a cat-and-mouse game. When the cancer becomes resistant to the drug, we would need a different molecular variant. And when it becomes resistant to the new drug, you would need the next generation drug. Like the Red Queens race, we have to keep running to remain still. In the decade since the discovery of Gleevec, 24 novel cancer-targeted drugs have been introduced and dozens more are in development. The 24 drugs have been effective against lung, breast, and prostate cancers, lymphomas, leukemias and sarcomas. Some inactivate oncogenes, others target oncogene-activated pathways. The Red Queens race applies to cancer screening and cancer prevention. Circles of relationships are powerful predictors of individual behaviors. The tobacco epidemic originated as a form of metastatic social behavior. Successful cancer-prevention strategies can lapse swiftly when social behavior changes. Thirteen Mountains The Human Genome Project was completed in 2003. It will be followed by the Cancer Genome Atlas project a compendium of every gene mutation in the most common form of cancer. Mutations in the cancer genome, Bert Vogelstein believes, come in two forms. Some are passenger mutations that have no impact on the biology of the cancer cell. Others are driver mutations that play a crucial role in the biology of a cancer cell. The mountains in the cancer genome, the most frequent mutations in a particular form of cancer, have another property. They can be organized into between eleven and fifteen key cancer pathways. The dysregulation of these core pathways poses an enormous challenge for cancer therapists. These changes provoke three directions for cancer medicine: Once we have identified the crucial driver mutations in any cancer, we will need to hunt for targeted therapies against these genes. We need to integrate the insights of cancer biology into cancer prevention to preempt the need for a million-person association study. Cancer screening can also be fortified by the molecular understanding of cancer. We need to integrate our understanding of abnormal genes and pathways to explain the behavior of cancer, renewing the circle of knowledge, discovery, and therapeutic intervention. Atossas War Imagine Atossa, the Persian queen who had breast cancer in 500 BC, traveling through time, appearing and reappearing in one age after the next. How would her treatment and prognosis changed in the last four millennia, and what happens to her later in the new millennium? In 2500 BC at Imhoteps clinic in Egypt, Imhotep provides a diagnosis, but there is no treatment, he says. In 500 BC, her Greek slave cuts her tumor out a primitive form of a mastectomy. In 400 BC, in Thrace, Hippocrates identifies her tumor as a karkinos. In AD 168, Claudius Galen says its a systemic overdose of black bile cutting the tumor out would not cure it. Medieval surgeons cut her cancer away with knives and scalpels. Some offer goat dung, lead plates, crab paste, and holy water as treatments. In 1778, at John Hunters clinic in London, her cancer is assigned a stage. If the tumor is local, he recommends surgery. For advanced cancers, he advises: remote sympathy. In 1890, at Halsteds clinic in Baltimore, her breast cancer is treated with radical mastectomy. In the early twentieth century, radiation oncologists try to destroy the tumor using X-rays. By the 1950s, her cancer is treated with a lumpectomy followed by radiation. In the 1970s, her surgery is followed by adjuvant combination chemotherapy to diminish the chance of a relapse. In the 1980s, besides surgery, radiation, and adjuvant chemotherapy, she is treated with hormonal and targeted therapy. In the mid-1990s, Atossas genome was sequenced and found positive for BRCA-1.ÂÂ   She is offered several targeted therapies to treat the illness. In 2050, Atossa will arrive at her oncologists clinic with a thumb drive containing the entire sequence of her cancers genome. The computer would identify the mutations and pathways that are causing the cancer. Therapies will be targeted against these mutations and pathways. She will start with one combination of targeted drugs, expect to switch to a second one when her cancer mutates, and switch again when the cancer mutates again.

Capital Punishment: The Best Solution Essay -- Capital Punishment, Dea

It is the the duty of the government to provide security for all individuals. Therefore, it is only a necessity, but also an obligation to get rid of those who impose threat or harm to any individual. Capital punishment is not always the most appropriate solution, but given the circumstances, it may be the most effective way to deal with criminals who threaten society. First of all, capital punishment would reduce taxes and makes prisons a much more effective place to hold criminals. This causes life imprisonment to become practically obsolete and prisons will be capable of functioning as a rehabilitation center. (the purpose of prison is to separate the criminals from the general population and to rehabilitate prisoners.) By implementing capital punishment, taxes would go down because there will be less prisoners to pay for. Also, capital punishment would get rid of â€Å"life imprisonment† (those who have committed a crime serious enough to get sentenced for life will be executed) and this is very important because recently, prisons have started to become a home for prisoners ins...

Our War On Drugs Essay

A drug can be described as a chemical substance that influences how an individual’s body and mind works (Rees 2005 p. 5). It is uncommon today to hear the word drugs on televisions and read them in magazines. Drugs are virtually everywhere and there is continual development of these drugs. They are used by people for various reasons ranging from medicinal to recreational purposes. Drugs that are taken as medicines include antibiotics and penicillin among others. However some drugs are illegal. They include: cocaine, ecstasy, marijuana, cannabis, heroin, crack, methamphetamines, LSD (acid), alcohol and magic mushrooms. These illegal drugs are also known as recreational drugs and many are gotten from plants growth in various parts of the world. Amphetamines are drugs that can be inhaled, or eaten in form of tables. Heroin is smoked or taken as an injection. Marijuana on the other hand consists of a brown resin. It is mostly smoked in cigarettes and it can also be eaten (Rees 2005 p. 30). Abuse of drug use is known as drug addiction. When a person constantly takes these illegal drugs for recreational purposes this addiction develops as a process and not instantly. Addiction to drugs affects individuals of multicultural, geographically diverse, across gender and racial classes. The initial steps are very moderate but their increased use results to a state of life threatening situation. Withdrawals are hardly achieved as the issue becomes of medical concern. Those who abuse drugs have their various reasons. They argue that drugs help them alleviate stress, boosts their morale and confidence, makes them feel good about themselves among many other things. Drug abuse has various adverse effects. Some of the effects include rises in blood pressure, vomiting, impairs memory and judgment capability of an individual. Other effects are poor decision making, accidents, impaired health and poor relationships. The consequences of these are physical, psychological and emotional instability on the drug abuser. The individual hence suffers from depression (Rick 2005 p30) A large number of people who abuse drugs decide to quit at some point but this is often difficult since once a person is addicted to drugs, it is almost impossible to avoid taking them as they mostly experience withdrawal symptoms. The symptoms are for instance body aches, sweating, and flu in the case of heroin. Nicotine on the other hand results to fatigue and premature aging affecting the skin, body shape and body weight. On the other hand, fast withdrawals could result to dangerous impacts. For instance tranquilizers could be dangerous resulting in high blood pressure, vomiting, temperature and stomach cramps (Rees 2005 p. 42) Our War on Drugs The war on drugs is a move undertaken by the United States including help from other participating countries whose priority is to eliminate trade in illegal drugs. It traces its origin way back in 1880 where there was a memorandum of understanding between United States and China to prohibit trade in opium between the two countries (http://www. nh-dwi. com/caip-213. htm). Today in America, mostly the youth experiment with these illegal drugs and they do it for various reasons. Some do it for recreational purposes whereas others are simply addicts as they cannot do without them. The United States government and the general public have become concerned about drug abuse and addiction. The government became more concerned about the issue in the 1960s when the youth mostly college students protested against the Vietnam war and in the 1960s and 1970s they began using licit and illicit drugs on a large scale for the first time (Fleckenstein Hanson & Venturelli 2005 p. 125). As a starting point the United States government introduced new strategies for tackling this issue of drug use and abuse. These strategies include demand reduction, inoculation, supply reduction, interdiction and drug courts. The use of drug courts has become a common strategy. The supply reduction is a strategy aimed at reducing and controlling supply of illegal drugs. Demand reduction aims at reducing the individuals’ tendencies to abuse drugs especially the youth. It places emphasis on reforming behaviors. Inoculation on the other hand attempts to protect drug users by informing them on their responsibilities. Drug courts on the other hand integrate incentives, sanctions, treatment and ensure that nonviolent drug addicts are placed in rehabilitation programs. Lastly interdiction is a policy aimed at stopping the supply of these illicit drugs (Fleckenstein, Hanson & Venturelli, 2005 p. 25). In the United States of America, there are quite a number of law enforcements Acts on drugs that have been established to control drug abuse. They include: Harrison Acts that looks into the production, sale, importation and distribution of opium. The other Act is the Narcotic Drug Import and Export Act aimed at alleviating use of narcotics but it is exceptional for medicinal and other legitimate use. Heroin Act of 1924 prohibited the manufacturing of drugs. The Marijuana Tax Act also controlled the production, sale and distribution of marijuana. The Opium Pappy Control Act restricted the cultivation of opium poppies in the United States except if one is licensed to do so. Narcotics control act on the other hand intended to establish suffer penalties to individuals who broke the marijuana or narcotics laws. Drug Abuse Control Amendments (DACA) was established to adopt stuff controls over barbiturates, amphetamines, LSD among others moreover; the Narcotic Addict Rehabilitation Act (NARA) was established to rehabilitate drug addicts in the three programs that is voluntary, sentencing to death addicts who are convicted and the pretrial civil commitment. In 1988, the Anti-Drug Abuse Act introduced the office of National Drug Control to oversee policies on research controlling drug abuse. Lastly the 2000 Drug Addiction Treatment Act gave a go ahead to physicians to prescribe narcotics for the treatment of oploid addiction (Fleckenstein, Hanson & Venturelli, 2005 p. 135). The white House National Drug Control Strategy in 2006 declared it stand and wish to balance the reduction in supply and demand of illegal drugs in the United States of America. It also outlined programs intended to curb abuse of drugs. In the same year, the National Drug Control Strategy pointed out its aim of supporting random student testing, intervention, screening, prevention, treatment and support for drug courts examining methamphetamines and making the United States southwest border secure (uninfo. state. gov/xarchives/display. gtm/? p. ). Another regulatory law enforcement body concerning drug abuse in the United States is the Drug Enforcement Administration (DEA). Its mission is to control drugs and provide laws and regulations regarding drug abuse. The National Drug control Strategy established a ten year plan to reduce drug abuse. It also aims at reducing America’s demand for drugs by offering treatment and supply through law enactments (http://www. usembassy-mexico. gov/bbfbfdossier-combDrogas. htm). The above drug laws indiscriminate use of drugs and it is through the legislation that licit and illicit drugs are determined. The government of the United States tries to meet public needs and control pressure through these rules and regulations. Due to the advancement in technology in today’s society, trained experts and government agencies provide information and protection on drug abuse. Are we winning the war on drugs? In my opinion, I do not believe that we are winning the war on drugs. I have based my judgment according to various reasons. Since the prohibition of drug abuse in 1937 in the United States of America; marijuana once considered for Mexican immigrants has been actively used by 20-37% of the youth in the United States. The same applies to the use of cocaine, ecstasy and methamphetamines (World Drug Report, 2000). The continual trade in drugs is also another factor that has severely affected efforts by the government to prevent drug abuse and addiction. The United States of America is largely affected more so because of its population and largest budget that focuses on enforcement. President George W. Bush in February 2002 established a National Drug Control Strategy based on the Principles of stopping the usage of drugs, disrupting the market and curing America’s drug addicts (Policy and Program Development, 2002). Evidence also shows that the criminal law in the United States has had only small success in preventing drug abuse. It is approximated that in 2004, 39% of students in the 12th grade used an illicit-drug, 34% was marijuana, cocaine 5% and LSD 2%. Also, those aged 12 and above who use illegal drugs as estimated by National Survey is 19. 5 million in the United States (Fleckenstein, Hanson & Venturelli, 2005 p. 140). In the United States, family structures have changed considerably having half of all women working outside home and the divorce rate is quite high. This has affected the nurturing of children by all these single parents. Family and friends have also contributed to the increasing drug abuses since they are ready to bail out and offer excuses for those who have been convicted (Fleckenstein, Hanson & Venturelli, 2005 p. 40). To conclude, it is therefore evident that the war on drugs is still far from being over. It is therefore essential that the society works hard to stop abuse of drugs which is causing deaths on a massive scale. It is essential for individuals to know that the effects of drugs on the social life, economic life, emotional and spiritual life are adverse. The extreme case of addiction to these drugs is the exposure of the individual person to death.

UBT1 Task 1 Essay - 922 Words

ZBT1 Task 1: Wave Physics Ian Trimble Student ID: 000352590 Introduction We benefit greatly the benefits of long distance communication, eating food from different parts of the countries without fear of spoilage, radiation treatment, and heating up food in a matter of minutes, and a myriad of other wonders all do the wonders of waves, be they sound waves as well as light waves. In this timeline, we will look at all of the different light waves, their history, and their benefits. Annotated Timeline 1800 – William Herschell was a contemporary of Sir Isaac Newton and was fascinated with one of Newton’s recent discoveries. Newton posited that when light was refracted through a prism, different colors of the visible light spectrum were†¦show more content†¦Otherwise their static. No one believed Maxwell, and Hertz set out to prove Maxwell right. Hertz used two rods to serve as a receivers. When the applied a spark to one of the rods, he could get it to jump to the other rod. Hertz discovered how to make the electric and magnetic fields separate themselves and travel freely. (The origins of radio, n.d. ) 1895 – X-rays were discovered accidentally by physicist Wilhelm Conrad Rontgen. Rontgen was working on a experiment and testing whether cathode rays could pass through glass. He noticed that a nearby tube emitted fluorescent glow of crystals. The air in the tube was released, high voltage applied, the same tube emitted a fluorescent glow. When Rontgen covered the tube in a heavy black paper, a green light could be seen. He concluded that a new light ray was being broadcast. Rontgen discovered that the light was very powerful and the same ray could pass through human tissue, but not through bones and metal objects. Medical applications were soon to follow. (History of radiography, ) 1900 – Gamma-rays were first observed when French chemist Paul Villard was investigating radium radiation. Villard observed that a photographic sheet was affected by radioactive materials when it was shielded by lead and iron. The radiation showed no magnetic deflection. The term gamma ray was coned from Ernest Rutherford several years later in 1903. Gamma-rays are