Jan 5, 2015. A New Cancer Hypothesis Update 2015 What is Cancer? The answer seems obvious, yet it is not. When studying a phenomenon, you ought to distinguish between obs. Six million Jews were gassed in fake shower rooms and subsequently vaporized by Adolf Hitler and the Nazis. It is historical fact that those who weren’t vaporized were turned into lampshades, soap and some even had their heads shrunk just for the lulz. These sad deniers try to cloak their insidious hate with rational sounding things such as wanting to see actual proof that this happened or to have these claims studied scientifically to see if it was even possible. This sort of anti-semitism has gone on far too long. Well guess what deniers, the proof has now been found showing that the Nazis not only used a popular insecticide to kill millions of Jews but their evil went even further.
Jul 19, 2017. 8. 1.2.2 Norton-Simon Hypothesis. One important reason the Skipper-Schabel-Wilcox model is so meaningful is that it concep- tualizes the tumor growth model e.g. exponential and tumor regression log-kill. Norton and Simon realized the importance of extending these observations to a Gompertzian. Larry Norton's multidimensional views of the world have come in handy for decades. As a child, he was rewarded by an art teacher for drawing objects from multiple vantage points. As a college student, he discovered a mistake in the tertiary structure of a chemical portrayed in a standard organic chemistry textbook. And as a clinical oncologist, he used mathematical models of tumor growth to create a new approach for treating breast cancer with drugs. For this, Norton—now deputy physician-in-chief for breast cancer programs at Memorial Sloan-Kettering Cancer Center in New York—was awarded this year's David A.
Nov 1, 2008. At Southern Research, Skipper had suggested that to cure L1210, it was necessary to eradicate the last leukemia cell because back extrapolations of survival after treatment suggested that one surviving cell was sufficient to kill a mouse. He offered the “Cell Kill” hypothesis, which stated that a given dose of. On this page we will discuss only Unix syslog analyzers with bias toward log analyzers written in Perl, as system administrators typically know this scripting language. For discussion of http log analyzers see web logs analyzers While there is no sure thing in security, syslog log analysis came pretty close. Unix syslog daemon provides wealth of information both for security and troubleshooting of problems. It permits creating centralized log server so that each syslog daemon sent to it its logs for correlated analysis. Contrary to popular opinion that does not explode using local log analyzers on each and every server.
Sep 27, 2009. LOG kill hypothesis ulliThe example shows the effects of tumor burden, scheduling, initiation/duration of treatment on patient survival. /li/ululliThe tumor burden in an untreated patient would progress along the path described by the RED LINE – /li/ululliThe tumor is detected using. In oncology, the fact that one round of chemotherapy does not kill all the cells in a tumor is a poorly understood phenomenon called fractional kill, or fractional cell kill. The fractional kill hypothesis states that a defined chemotherapy concentration, applied for a defined time period, will kill a constant fraction of the cells in a population, independent of the absolute number of cells. In solid tumors, poor access of the tumor to the drug can limit the fraction of tumor cells killed, but the validity of the fractional kill hypothesis has also been established in animal models of leukemia, as well as in human leukemia and lymphoma, where drug access is less of an issue.
Abstract. Optimal control techniques are used to develop optimal strategies for chemotherapy. In particular, we investigate the qualitative differences between three different cell-kill models log- kill hypothesis cell-kill is proportional to mass; Norton–Simon hypothesis cell-kill is proportional to growth rate; and, Emax. The first of Skipper’s laws is that the doubling time of a tumor is constant, A plot of the number of cells in the tumor over time on a semi-log graph forms a straight line. Working with animals, Skipper showed that organism death happens when the tumor size reaches a certain fraction of the mouse weight, which means survival is associated with the number of tumor cells. This hypothesis states that tumor cells are killed in response to a chemotherapeutic agent at a rate directly proportional to the tumor growth rate at the start of treatment. Postulate that “a given dose of a given drug will kill approximately the same fraction, not the same number, of widely different-sized tumor cell populations —so long as they are similarly exposed and both the growth fraction and the proportion of drug-resistant phenotypes are the same.” This model resulted in development of the log kill hypothesis. This hypothesis predicts that the tumor cells develop resistant phenotypic variations towards chemotherapeutic agents. This resistance is independent of the chemotherapeutic agent and dependent on the number of cell divisions that occur after treatment begins.
Oct 20, 2004. The Norton–Simon hypothesis flew in the face of conventional views, which held that tumor growth is exponential and that chemotherapy kills in log intervals, meaning it kills constant fractions of tumor. When it was published in the 1970s, the hypothesis was met with such fierce hostility that Norton. I'm not saying we should stop, but I think we should at least examine which lies we tell and why. We were all lied to as kids, and some of the lies we were told still affect us. So by studying the ways adults lie to kids, we may be able to clear our heads of lies we were told. I'm using the word "lie" in a very general sense: not just overt falsehoods, but also all the more subtle ways we mislead kids. Though "lie" has negative connotations, I don't mean to suggest we should never do this—just that we should pay attention when we do. One of the most remarkable things about the way we lie to kids is how broad the conspiracy is. " you'll probably say "Ask your parents."Since we all agree, kids see few cracks in the view of the world presented to them.
Cancer Chemotherapy Targets for selective toxicity target rapidly dividing cells? cancer cells are not the only replicating cells e.g. intestinal epithelia, bone marrow, mucosal, hair follicle cells are all rapidly dividing as well not all cells in a tumor are replicating not all cancer cells have escaped normal growth control. Optimal control techniques are used to develop optimal strategies for chemotherapy. In particular, we investigate the qualitative differences between three different cell-kill models: log kill hypothesis (cell-kill is proportional to mass); Norton-Simon hypothesis (cell-kill is proportional to growth rate); and, Emax hypothesis (cell-kill is proportional to a saturable function of mass) For each hypothesis, an optimal drug strategy is characterized that minimizes the cancer mass and the cost (in terms of total amount of drug). The cost of the drug is nonlinearly defined in or objective functional and linearly defined in the other. Existence and uniqueness for the optimal control problems are analyzed. Each of the optimality systems, which consists of the state systen coupled with the adjoint system, is characterized.
Mar 10, 2017. Skipper–Schabel model; Skipper–Schabel–Wilcox model The log-kill hypothesisproposes a model for the effect of cytotoxic chemotherapy on tumor size. It states that a given dose of chemotherapy. captains of industry essay English comp ii onl essay 2 6-27-04 marketing and consumerism of makeup advertisements today’s advertisement industry is a major part of our daily. Title:persuasive and argumentative essay topics air date: 1 day description: words for students of english: a vocabulary series for esl. Fiction and non-fiction for ap literature and composition engage in deep and wide reading, comparison and contrast with other authors/poets, critical leading to an interpretive conclusion about the meaning and value of a piece of writing. log kill hypothesis Students will write an argumentative essay arguing which spirit had the greatest influence in changing scrooge these sentence starters will assist students to. Give reasons for your opinion, 2006 am toefl essay ban smoking from public places toefl essay topic in some country, smoking ban in public places has been a hot issue these last months not only in malta but gre argumentative essay topics.
In oncology, the fact that one round of chemotherapy does not kill all the cells in a tumor is a poorly understood phenomenon called fractional kill, or fractional cell kill. The fractional kill hypothesis states that a defined chemotherapy concentration, applied for a defined time period, will kill a constant fraction of the cells in a. Targeted agents: Act against pathways that lead to: uncontrolled proliferation, loss of cell cycle inhibitors. Dosage factors:- Dose escalation Reducing interval between treatment cycles Sequential scheduling of either single agents or of combination regimens Cancer Chemotherapy After completion of mitosis, the resulting daughter cells have two options: (1) they can either enter G1 & repeat the cycle or (2) they can go into G0 and not participate in the cell cycle. Loss of cell death regulation, capacity to replicate chromosomes indefinitely invade, metastasize & evade the immune system 3. Biological therapies – includes 2 & gene therapies Therapeutic delay Tumor response Anti cancer drug toxicities Gradation of toxicity: do not require treatment require symptomatic treatment, not life threatening Potentially life threatening if left untreated actually life threatening death How anti – cancer drugs work:- Interaction of drug with target cascade Cell -death – “Execution phase” Proteases, nucleases and endogenous regulators of cell death pathway are activated. Growth fraction - at any particular time some cells are going through the cell cycle whereas other cells are resting. P210 bcr –abl fusion protein tyrosine Kinase drives CML HER – 2 / neul – breast cancer Combination of drugs:- Efficacy Toxicity Optimum scheduling Mechanism of interaction Avoidance of arbitrary dose changes. The ratio of proliferating cells to cells in G0, is called the growth fraction. A tissue with a large percentage of proliferating cells & few cells in G0 has a high growth fraction.
This model of tumor growth, formulated and popularized by investigators at the Southern Research Institute, is commonly called the log-kill model. It would be informative to examine these in some detail, not only to illuminate this one hypothesis but also to show the relevance of growth curve analysis to clinical problems. Roadkill refers to an animal or animals that have been struck and killed by motor vehicles on highways. It is important because of the animal suffering, loss of wild animals, road safety, and the economic impact on both drivers and road management. For this reason it has increasingly become the topic of academic research to understand the causes, and how it can be mitigated. During the early 20th century, roadkill or "flat meats" (or "highway pizza") became a common sight in most industrialized First World nations, as they adopted the internal combustion engine and the automobile. One of the earliest observers of roadkill was the naturalist Joseph Grinnell, who noted in 1920: "This [roadkill] is a relatively new source of fatality; and if one were to estimate the entire mileage of such roads in the state [California], the mortality must mount into the hundreds and perhaps thousands every 24 hours." In Europe and North America, deer are the animal most likely to cause vehicle damage. In Australia, specific actions taken to protect against the variety of animals that can damage vehicles – such as bullbars (usually known in Australia as 'roo bars', in reference to kangaroos) – indicate the Australian experience has some unique features with road kill.
Cell-cycle specificity. cell-cycle specific drugs. act only during certain phases of the cell cycle; more effective against high-growth fraction tumors. cell-cycle nonspecific drugs. used in both high- and low-growth fraction tumors. Log-kill hypothesis. cytotoxic drugs kill a fixed percentage of tumor cells. not a fixed number. Unformatted text preview: ANTICANCER DRUGS Log-kill hypothesis Cytotoxic drug actions follow first-order kinetics- kill a fixed % of a tumor cell population, not a fixed number of cells Anticancer Drug Principles Growth fraction Cytotoxic drugs are more effective against tumors with a high growth fraction (large % actively dividing). Anticancer drugs are more toxic to normal cells with high growth fraction (eg., Bone marrow) Resistance to Anticancer Drugs Change in target enzymes or receptors; etopoxides, MTX, alkaloids, steroid receptors Decreased drug accumulation via increasing the expression of glycoprotein transporter, or reduce permeability : MTX, alkylating agents, dactinomycin Formation of drug inactivating enzymes - purine and pyrimidine antimetabolites Production of “trapping agent” alkylators, bleomycin, cisplastin, doxoburicin Resistance to anticancer Drugs Increased nucleic acid repair: alkylating agents, cisplastin Reduced activation of pro-drugs: purine and pyrimidine antimetabolites Bleomycin Antibiotic : acts in phase-complexes with Fe and O2, causing DNA strand scission Rx uses: Hodgkin’s, testicular, head, neck, skin CA Adverse effects: pneumonitis, pulmonary fibrosis, mucocutaneous reactions (blisters), alopecia, hypersensitivity BLEOMYCIN • The anticancer drug bleomycin is actually a mixture of several glycopeptyde antibiotics isolated from a strain of the fungus Streptomyces verticellus. MECHANISM • Binds to DNA - produces single- and double-strand breaks (free radical formation) interfere with cell growth. Cyclophosphamide Alkylating agent attacks guanine N7, causing dysfunctional DNA Rx uses: non-Hodgkins lymphoma, breast CA Adverse effects: BMS, mucosis, hemorrhagic cysttis (mesna, traps acrolein and is protective), hepatotoxicity (high dose) CYCLOPHOSPHAMIDE DNA crosslinks Cell death (Takimoto, et al., 2008) Cisplastin Alkylator : alkylating agent - cross-links DNA strands Rx uses: testicular, ovarian and bladder, lung CA Adverse effects: neusea, vomiting (use use ondansetron), nephrotoxicity (amifostine) , neurotoxicity (deafness) Methotrexate (MTX) Antimetabolite (S phase): inhibits DHF reductase Rx uses: leukemias, lymphomas, breast CA Adverse effects: mucositis, crystalluria, folic acid rescue 6-Mercaptopurine (6-MP) Purine antimetabolite Rx uses: Acute lymphocytic leukemia;, immunosupression (azathioprine forms 6 – MP) Adverse effects: hepatotoxicity (jaudice, necrosis), GI distress Doxorubicin Intercalator, forms free radicals, inhibits topoisomerase Rx uses: breast, endometrial, lung, ovarian CA TOXICITY OF ANTICANCER DRUGS Rapidly proliferating cells such as the bone marrow, GI tract mucosa, hair follicles, and gonads are most sensitive to cytotoxic drugs Most often bone marrow suppression (BMS) is dose -limiting.
Looking for fraction kill hypothesis? Find out information about fraction kill hypothesis. A principle of chemotherapy that a uniform dose of a drug will destroy a constant fraction rather than a constant number of tumor cells regardless of the. Explanation of fraction kill hypothesis. That I can account for his next act, which was in the nature of a last resort--a sort of forlorn hope, which could only have been born of the belief that if he did not kill me quickly I should kill him.
Several cycles of treatment may be necessary to achieve a substantial reduction in tumor size. The chemotherapeutic regimen, especially when one is deal- ing with large, solid tumors, probably should include agents that have cytotoxic activity against resting cells. THE LOG CELL KILL HYPOTHESIS. Cytotoxic drugs act by. He is known as one of the wealthiest men in the United States, with a fortune that is reported to be approximately $45 billion. He wants 99% of his wealth to go to the Buffett Foundation, which mostly serves family planning clinics. His company Berkshire Hathaway has gained overall value since 9/11. Bush flew later that day for “safety.” As the attack began, Anne Tatlock was to this same location. where was Warren Buffett the morning of 9/11 and what was he doing? She arrived at the base to join Buffet in time to watch the second plane make a direct hit on the tower precisely where her office complex was located. Buffett was reportedly at his home in Omaha, Nebraska watching TV when he heard about the terrorist attacks. On the morning of the September 11, 2001 terrorist attack on America, the attack commenced, the world’s second most wealthy man was already at the U. He was getting ready to host his “last annual golf charity event” which just happened to be at the U. Strategic Command headquarters located at Offutt Air Force Base in Omaha. on the morning on 9/11, a small group of top financial CEO’s with offices in the WTC, were flown to the nerve center of U. air defenses, for the “Charity Classic” golf event (fund raiser benefit for youth groups). Tatlock such a lucky person for being invited to this charity event that morning? Tatlock not only works in the World Trade Center, but her offices were right where Flight 175 crashed into the South WTC Tower. Strategic Command at Offutt Air Force Base in Nebraska ► The United States Strategic Command, or USSTRATCOM, is headquartered at Offutt Air Force Base, Nebraska.
But even more instructive is his personal model—not only the Norton-Simon Hypothesis—of how to live and approach science, biology, patients and their families, as well as the broader community. He shows that with energy, enthusiasm, optimism, intellect, and hard work we can make the world better. Clifford A. Hudis, MD. Use the links below to get the latest version of the KILL game. If you are Windows PC, Mac or Linux user, then just click Download to get the game. Please note that this game may ask for additional in-app purchases and permissions when installed.
Sep 17, 2008. The 1940s marked the beginning of an era of important discoveries that contrib- uted to modern concepts underlying the current practice of cancer chemother- apy, such as the log kill hypothesis reported by Skipper, the Norton-Simon hypothesis, and the Goldie-Coldman hypothesis. The early success of. Test Log T-98816-OC108/682 Cross-SCP Termination Testing for SCP-682 Due to the highly aggressive, adaptive, and intelligent nature of SCP-682, termination testing has been ordered, with clearance from O5 Command. SCP-682 is in a pool of grey and black liquid, with no observable life signs. With major concerns raised about possible developed immunities (due to the failure of SCP-409) and possible adaptations, all tests must first be carried out on tissue samples taken from SCP-682. D-Class issued to physically verify SCP-682 termination, with two Agents supervising. This step may be bypassed only by O5 Command order. D-Class enters three steps into the containment area when SCP-682 rapidly rises and attacks D-Class personnel. Item: SCP-689 Tissue Test Record: Overridden by O5-Command Termination Test Record: SCP-682 exposed to SCP-689. SCP-682 breaks containment and escapes, killing one Agent in the process. Remaining Agent killed by SCP-689 due to accidental observation during testing.
In other words, we are less outraged by the regular killing of mothers, daughters, fathers, sons, sisters and brothers in Pakistan by our drones and are less prone to become active against that than we care about a slain lion. Because turning people in Pakistan into foreigners by assigning special vocabulary like "honour. The log-kill hypothesis proposes a model for the effect of cytotoxic chemotherapy on tumor size. It states that a given dose of chemotherapy kills the same fraction of tumor cells regardless of the size of the tumor at the time of treatment. Experimental and mathematical models have attempted to describe the fundamentals of tumor cell growth and kinetics. From these systems arose an improved understanding of tumor growth characteristics, a foundation for the key principles of chemotherapy, and, eventually, recognition of the importance of dose scheduling. The Skipper-Schabel-Wilcox model is one of the most influential and pioneering experiments in the history of oncology.
May 6, 2015. tumour cell burden and the population kinetics of the cancer cells are important determinants of the success of antineoplastic chemotherapy, and directly determine the dosing schedule; magnitude of a tumour cell kill is a logarithmic function i.e. a 3-log-kill dose of an effective drug will reduce the cancer cell. Toxic effects of chemo mandate lag between treatment so cancer can regenerate.1. Tumor that usually does not cause necrosis of neighboring tissue, metastasize to other organs or result in death (although some may mutate to become malignant) *usually end in -oma (except melanoma and glioma-doesn't metastasize but can cause death)Most chemo agents kill 99.99% of cacner cells, but the remaining 0.01% may cause recurrence (tumor regrowth or metastasis). A) Inhibit topo II; B) high-affinity binding to DNA through intercalation; C) Binding to cell membranes, althering fluidity and transport; D) Generation of semiquinone free radicals and oxygen free radicals that damage DNASomethign crucial to functioning of that organism/cell, but missing frmo human body and use a drug to disable it *Problem is that cancer cells are human cells which makes finding something unique difficult1. Alkylation of DNA (N7 of G, O6 of G, N1 and 3 of A, N3 of C) blocking replication machinary 2. Alkylation of cellular proteins by reacting with nucleophiles such as sulfhydrul, amino, hydroxyl, carboxyl, and phosphate groups *most are bifunctinoal 1. Carmustine (BCNU); lomustine, semustien, streptozocin 3. Alkylate G at N7 primarily, but toxicity is from minor G O6 alkylation causing CG crosslinks inter or intrastrand 4.
Cancer log-kill revisited. Norton L1. Author information 1From the. But even more instructive is his personal model-not only the Norton-Simon Hypothesis-of how to live and approach science, biology, patients and their families, as well as the broader community. He shows that with energy, enthusiasm, optimism. I am amazed that this Clovis as mammoth murderer to extinction idea still has traction. I am presenting this here not to convince the reader, but to show that the popular idea of humans as mammoth “extinction machines” has another, valid, side to it. I was not looking for this article or anything along these lines at the time I found it (a couple of months ago) – but it blew me away, that two BIG names in this area of research (Grayson and Meltzer) had such a paper out there. In my opinion, this paper eviscerates the Overkill hypothesis. See what you think: See “A requiem for North American overkill” Grayson and Meltzer 2003.
Test Log T-98816-OC108/682. Cross-SCP Termination Testing for SCP-682. Due to the highly aggressive, adaptive, and intelligent nature of SCP-682, termination testing. The "Kill the Winner" hypothesis" or KTW is a model of population growth involving prokaryotes, viruses and protozoans. It is based on the concept of prokaryotes taking one of two reactions to limited resources: "competition", that is, that priority directed to growth of the population, or a "winner"; and "defense", where the resources are directed to survival against attacks. It is then assumed that the better strategy for a phage, or virus which attacks prokaryote, to concentrate on the "winner", the most active population (possibly the most abundant). This tends to moderate the relative populations of the prokaryotes, rather than the "winner take all". The model is related to the Lotka Volterra equation.