Part 1 – Answer the following 4 questions (worth 10% each):
Please limit to a single page per answer.
Explain why DNA repair is a critical tumor suppressor function. Using an example tumor suppressor gene, detail how it impacts a specific DNA repair mechanism. Classify its impact in at least one cancer/cancer syndrome, and present an actual or theoretical therapeutic strategy for treating patients with this syndrome
You are a clinician-scientist that has a patient with colon cancer. Identify four possible oncogenes that are both commonly affected in colon cancer and are actionable for treatment with available drugs either directly or indirectly. Identify two appropriate FDA-approved kinase inhibitor drugs for counteracting the gain of function for each of these four oncogenes. Identify which of the most common cancer-inducing amino acid mutations on these four oncogenes you would initially screen for (3 mutations for each oncogene) in your patient to identify which kinase you will target with a drug that you would first prescribe for your patient. (You may find the www.onconet.ca, www.kinasenet.ca, www.drugkinet.ca and http://cancer.sanger.ac.uk/cosmic websites as well as the lecture notes helpful.)
Prostate cancer is exquisitely dependent on androgens for growth and survival.
- Describe the endocrine regulation of androgen levels by the hypothalamic pituitary axis.
- Describe the androgen/androgen receptor signalling pathway
- Name two molecular targets for treatment of prostate cancer and how drugs that target these proteins work to block androgen dependent growth of prostate cancer
A patient with renal failure underwent a kidney transplant using an organ obtained from the victim of a car crash. Six months later the patient was diagnosed with a malignant lesion in the donated kidney that the pathologist determined to be of lung origin. Subsequent investigation revealed that the organ donor had been successfully treated with radiation for lung cancer several years earlier.
- A) In terms of the prevailing model of cancer immune surveillance, explain the history of the cancer from its origin in the donor to its re-emergence in the transplant recipient. (8 marks)
- B) The treating physicians discussed withdrawal of immune suppression as a possible treatment strategy. Explain the potential benefits and downsides of this treatment from an immune perspective. (2 marks)
Part 2 – Answer the following 3 questions from instructors who gave two lectures (worth 20% each): Please limit to two pages per answer
What is the difference between the Th1 response and the Th2 response?
- Explain the mechanism behind these responses.
- Describe one disease caused by or exacerbated by either a faulty Th1 or Th2 response and suggest potential therapeutics to control the disease
Please describe the compartments of a typical differentiation hierarchy, their characteristics and how their output is controlled. Write about the differences in homeostatic and stress conditions.
The binding of a growth factor to its receptor leads to a series of signalling events culminating in regulation of transcription factors in the nucleus (as one of several potential end points of the pathways). When a cell encounters conditions that cause it to undergo apoptosis, a series of signalling events occurs which eventually leads to activation of caspases.
Summarize the key events in these two pathways – i.e. a) pick one growth factor receptor being activated leading to a transcriptional event and b) describe a pro-death environment activating the intrinsic pathway of apoptosis that activates specific caspases.
Compare and contrast these two different signalling networks by pointing out how protein-protein interactions and post-translational modifications may be playing key regulatory roles.
Cosmetics has been near and persisting changes since 3100-2907 BC. People in Egypt began with creams to keep their skin delicate and sparkling. Before long different nations began made their very own type of cosmetics. Cosmetics has been around for a considerable length of time is still generally utilized today. The egyptians utilized dull green hues for eyeshadows and for mascara they would tint eyelashes with kohl. At times they would utilize the kohl for eyeliner. This kohl was really produced using sediment. In Rome they had similar thoughts on how apply cosmetics however the manners in which they did it were hazardous. The Romans trusted that to be rich your skin must be pale. To achive this look they would utilize chalk and even white lead. Since these strategies were so unsafe numerous ladies kicked the bucket because of lead harming it caused a considerable measure of medical issues, for example, hair loss,stomach issues and demise. Inevitably they began making cosmetics items from regular sustenance fixings. In the victorian time it was trusted that in the event that you were wearing cosmetics then you were a whores or on-screen characters. Any overwhelming cosmetics or even a slight shading change in hair, they would be looked downward on. At this point cosmetics was advancing and individuals became weary of utilizing hurtful synthetic substances all over. Ladies had quit utilizing kohl for their eyelashes and began utilizing hot wax and different oils. Rather than utilizing flour to powder noses Max Factor made a press powder around 1914. In film cosmetics performers would as a rule do their own cosmetics which made them simply get anything. The majority of the items they utilized contained lead and mercury. To get the coveted look they would utilize a to a great degree overwhelming oil paint that was pink in shading to re revise the lighting from the film gear. On the off chance that the paint was connected to daintily the performers would look pale. To attempt to battle that they would likewise utilize dark and red liners to endeavor to burrow out their eyes. They would sweat under those stage lights and each blemish all over would appear. Max Factor and George Westmore understood this was an issue so Max made an exceptional sort of oil paint that was a lighter item. You could develop it to anyway thick you needed to and it scarcely demonstrated any brutal lines. He would set that oil paint with his "flapjack" cosmetics which was extremely his new squeezed powder. Regardless they utilized the red and dark liners to dig out their eyes. His hotcake cosmetics was utilized in Vogues of 1938 and Goldwyn's Follies. It was just utilized in motion pictures yet soon everybody was wearing it offscreen. Max Factor proceeded to make his magnificence domain. He began making establishments, lipsticks, eyeshadows, cheek tints and so forth. George Westmore went from a wig producer to a cosmetics craftsman. George imagined a ton of tips and traps for film cosmetics. Indeed, even the creation of false lashes. George opened a modest cosmetics studio in 1917. He had huge customers like Mary Pickford. He really figured out how to "counterfeit" her twists ordinary. Film cosmetics has not changed. They utilize more secure materials that have really been tried. Additionally, they have likewise gotten more inventive. For instance they have possessed the capacity to make elastic pieces to join onto the skin and how to paint countenances to look more like a character or a beast. Soul gum was likewise acquainted with the cosmetics world alongside latex. The latex works extraordinary for making little wrinkles. Lon Chaney used to utilize wire and bathroom tissue to bend his nose up for one of his jobs. It was an exceptionally unsafe approach to bend his nose in light of the fact that the wire would influence his nose to drain. The first occasion when that repulsiveness cosmetics was utilized in a film was Nov. 30th in 1925 with the Phantom of the Opera. With the end goal to get the cosmetics impact, Lon Chaney would put his wig on alongside a prosthetic piece for his temple. He utilized dark shadow for the underneath his eye to make it resemble his eye was pulled down with a tad of white on his base lash line to influence the eye to seem greater. Additionally, he utilized a fish skin material and stuck it down with soul gum. They attempted to stick his nose down with simply soul gum yet it would dependably fall down. They had wires running from his nose into his wig piece and the wire was anchored with the fish skin. They likewise had little wires for his mouth. His face had infinitesimal wrinkles everywhere white and dark cosmetics was utilized to make him look a bit deadish. At that point the last advance was to give him new teeth to finish the look. In 1935 The Bride of Frankenstein was the following film to utilize enhancements cosmetics. Regularly performing artists would do their very own cosmetics however for this motion picture they acquired a cosmetics craftsman named Jack P. Penetrate. Jack made two scars under her button that went into her hair. The scar making process took around 60 minutes. They secured her face with establishment lipstick and false eyelashes. At that point for her hair they simply brushed her hair upwards onto a little enclosure and included dark streaks. The animal of the Black Lagoon in 1954. The outfit was produced using shaped elastic wipe. In 1973 The Exorcist utilized a type of temple piece. They concealed her eyebrows. Likewise, they utilized latex to make the cuts all over and a smidgen of wound hues around her face to make her look had with the assistance of contacts. To make the regurgitation they utilized pea soup. In 1977 The Incredible Melting Man turned out. For this cosmetics look they gave the on-screen character a larger than usual head protector that they painted to look skeletal then with a tissue tone. At that point they would put syrup and paint everywhere throughout the cover. Each take they would need to apply to an ever increasing extent so it would look new. Next is Alien from 1979. For this film they utilized a delicate demonstrating material and snake vertebrates. Likewise, they utilized cooling tubes from an auto. In 1984 Nightmare on Elm Street wound up well known due to Freddy's consumes over his face. To make these consumes the cosmetics craftsman utilized individual pieces to lay on the performing artist's face. To begin with, he began off by anchoring an uncovered top on with soul gum then latex. At that point needed to shut out the eyebrows and his facial hair with a paste stick so the prosthetic pieces would not stall out to the hair when he stuck them down. He put the head piece on first, at that point the neck piece, he would anchor the face piece and after that the button piece. All together there was 11 pieces that were put on. The cosmetics took around three hours to put on and taking it off. At the point when the majority of the edges were mixed and secure he would go over the majority of the "consumes" with red paint then softly with a white shading. The face pieces were etched out of silicone so they wouldn't need to begin starting with no outside help every day. In 1990 Edward Scissorhands turned out and they got a workman to take a shot at his hands. For his cosmetics he has a pale shade all over, the underneath of his eyes have dull sacks and that should be possible with only a dark eyeshadow that is daintily tidied. For the cuts all over a little layer of latex is all the sfx cosmetics this motion picture required. In 2000 The X-Men was discharged. For Mystique they had a full body cast to shape the 110 pieces. Around 60% of her body was shrouded in prosthetics. They plastered throws of generally the majority of the cast individuals. Likewise, they did throws for Wolverine's hands. The cosmetics took around seven hours for just Mystique. 2004 Hellboy was discharged. The cosmetics for Hellboy took four hours. First they utilized all froth pieces. They connected his back piece and put it over his make a beeline for join to his chest. The last pieces that were connected were the facial prosthetic pieces that just left his lower lip. He was then painted all red.They would append the lower lip part just before they began shooting so he could eat or drink. Embellishments cosmetics has become further developed as the time passes by. The craftsman presently have the decision to make prosthetics to make their activity less demanding. The assortment of cosmetics decisions are bigger. For instance artificially glamorizing in now a probability. Rather than giving paint the majority of the prosthetics, it sets aside less opportunity to enhance with Photoshop than to paint each individual piece. When you're finished digitally embellishing you can invest more energy concentrating on the more vital points of interest.>GET ANSWER