Star1234 Posted April 20, 2009 Author Report Share Posted April 20, 2009 Yes. Though I'm not clear on why adenovirus would be able to replicate only if p53 was suppressed. I'm no virologist, but wouldn't the surface receptors on both cancer and normal cells be crucial to this? (So, maybe it work on adenoma/adenocarcinomas...) Ok, so while the virus would be able to get into cancer and normal cells equally well (since, like you said, cancer and normal cells would still have similar surface receptors), it would only be able to actually replicate and lyse cancer cells. Why? Viruses usually rely on highjacking the host cell's replication machinery in order to replicate (such as its RNA polymerases, etc). As well, one of p53's functions is to inhibit the cell cycle when it feels like something's not right. So if the virus was to infect a healthy cell, p53 would be activated, which would stop the cell cycle and prevent the virus from further replicating. However, there would be no p53 to stop the virus in cancer cells, therefore replicating, lysing, and killing the cancer cells. Finally, most viruses prefer actively replicating cells to infect, so this would also push the virus to select for cancer cells (which replicate like craaazzzy). Link to comment Share on other sites More sharing options...
A-Stark Posted April 20, 2009 Report Share Posted April 20, 2009 Ahh, that makes sense, though epithelial tissue is about as actively replicating as you can get outside a malignant neoplasm. Clearly the issue of surface receptors would make this approach considerably less useful for poorly differentiated growths. Link to comment Share on other sites More sharing options...
RobynM Posted April 20, 2009 Report Share Posted April 20, 2009 Adenoviruses actually bind to a receptor called CAR which can be downregulated in a lot of cancer types but people are working to retarget specific adenoviruses to be more specifically bound and taken up by different cancer cell types (a la Herceptin binding to HER2) However most of thse treatments are being used for gene therapy (putting a cancer promoter drivine suicide gene into the cell) and not oncolytic viral therapy. Also the ONYX15 trials (those adenviruses that supposedly only replicate in p53 negative tumor cells) were actually found not to be specific for only p53 negative tumors. It turns out that E1B regulates a lot of other cell processes independent of p53 that regulate the viruses replication. I work in a lab that works on transcriptional and translational targetting of adenoviruses for gene therapy application in breast cancer BTW... Link to comment Share on other sites More sharing options...
Star1234 Posted April 20, 2009 Author Report Share Posted April 20, 2009 What if cancer cells mutate to nullify this virus? And what if the virus mutates and goes rogue? And what is the cell surface receptor that adenovirus use anyways to enter host cells? If it enters cancerous and non-cancerous cells alike, can it undergo recombination to mutate into other forms? That's why they mutate multiple genes to make the effectiveness of the virus greater. So, for example, you delete one gene so the virus can only replicate in p53-null tumors, you place another gene under a tumor-specific promoter etc. And even if the virus was to mutate into another form, chances are that the mutation of the virus would be disadvantageous to the replication of the virus....BUT even if it did somehow cause the virus to replicate better, you always have a "suicide gene" inserted within the virus, where you could kill it with a particular drug if you really needed it to. But cancer cells are known to lose surface receptors. So would it still work in that case? If the cancer cells do not lose surface receptors, would it work on other types of tissue too? ex: glial or meningeal tissue of the brain. Oh yea thats the other problem. Do adenoviruses cross the blood-brain barrier? And even if the cancer cells did lose certain surface receptors, you could alter the virus to be compatible with the surface receptors of the tumor (ie. if the tumor overexpressed the estrogen receptor then you could alter the virus so that it needed to recognize the estrogen receptor to enter). Oh yea thats the other problem. Do adenoviruses cross the blood-brain barrier? And actually, ya, these viruses do cross the blood-brain barrier. The first clinical trials for these viruses was done on patients with head and neck cancers actually Link to comment Share on other sites More sharing options...
deeman101 Posted April 20, 2009 Report Share Posted April 20, 2009 Yes I lack experience in cell cycle based cancer treatment. My lab works with cytotoxic and antiangiogenic chemo drugs. They kind of use the replication process, but not in the same way as what you guys are talking about. Link to comment Share on other sites More sharing options...
Star1234 Posted April 20, 2009 Author Report Share Posted April 20, 2009 Also the ONYX15 trials (those adenviruses that supposedly only replicate in p53 negative tumor cells) were actually found not to be specific for only p53 negative tumors. It turns out that E1B regulates a lot of other cell processes independent of p53 that regulate the viruses replication. Oh ya, I totally agree that ONYX15 wasn't perfect. But that's why it was only the first generation oncolytic virus produced. I think the one that is currently approved in China is called H101 and it also has the E3 gene deleted (which is an inhibitor of the viral immune response) on top of the E1B gene. But now they are trying to use better viruses such as HSV-1, or VSV which is naturally oncolytic. Great discussion though guys Link to comment Share on other sites More sharing options...
RobynM Posted April 20, 2009 Report Share Posted April 20, 2009 Yeah, I think that generally simpler viruses that adenoviruses tend to be better than suited for oncolytic therapies while adenoviruses, because of their ability to carry such large DNA inserts and the fact that they don't integrate are more suited for gene therapy based techniques. The head PI leading the H101 trials actually gave a talk in our department a few months ago and some other graduate student and I were able to sit down and speak with him for a bit. Interesting stuff they have going on, for sure! Link to comment Share on other sites More sharing options...
Star1234 Posted April 20, 2009 Author Report Share Posted April 20, 2009 The head PI leading the H101 trials actually gave a talk in our department a few months ago and some other graduate student and I were able to sit down and speak with him for a bit. Interesting stuff they have going on, for sure! Oh man, I'm soooooooooooo jealous Link to comment Share on other sites More sharing options...
Jochi1543 Posted April 20, 2009 Report Share Posted April 20, 2009 Yeah, this reminds me of that group of docs/nurses who got kidnapped somewhere like Somalia recently...no MSF for me, lol. LOL, I post this and look what happens the next day: http://www.cnn.com/2009/WORLD/africa/04/19/somalia.hostages/index.html Link to comment Share on other sites More sharing options...
jdai Posted April 20, 2009 Report Share Posted April 20, 2009 My parents threatened to disown me if I don't become a doctor. Hah too bad for them! I got in! Link to comment Share on other sites More sharing options...
Jacques Cartier Posted April 20, 2009 Report Share Posted April 20, 2009 LOL, I post this and look what happens the next day: http://www.cnn.com/2009/WORLD/africa/04/19/somalia.hostages/index.html lol wow - it seems like they don't have the respect from locals they had a couple years ago! There are still plenty of places that MSF works where they aren't in immediate danger of being kidnapped (or at least minimal). You really have to respect those docs that are willing to work in those conditions though when they could be living with the higher-ups in a developed country instead. Link to comment Share on other sites More sharing options...
stellargellar Posted April 20, 2009 Report Share Posted April 20, 2009 I want to study the wonders of science especially the human body. Link to comment Share on other sites More sharing options...
apache Posted April 20, 2009 Report Share Posted April 20, 2009 good money, can work anywhere, very high people contact, i enjoy building friendship with people and watching their lives improve, id like to enjoy life and have the freedom to do it Link to comment Share on other sites More sharing options...
youbrokeit Posted April 29, 2009 Report Share Posted April 29, 2009 1) It's interesting, there's no 'end point' to the profession. You can always learn/work on something new or change your scope/area of practice (and not have to leave work entirely to go back to school). 2) It's challenging. Conquering something difficult (physically or intellectually) is a staple of most entertainment. It's a bonus to get to do it at work as well. 3) Lasting accomplishments. Someone is alive/can see/can walk/etc. thanks to what you did at work. 4) I like people. Fixing them seems like a good career choice. 5) The money is good (and stable), so I don't need to worry about providing for my family and can have some fun when I'm off Other possible career choices: engineer (if I could stay technical), trades Link to comment Share on other sites More sharing options...
Rock* Posted May 7, 2009 Report Share Posted May 7, 2009 My parents threatened to disown me if I don't become a doctor.Hah too bad for them! I got in! Jesus Christ! That's like the worst reason to go for med Link to comment Share on other sites More sharing options...
Hopeful Med Posted May 7, 2009 Report Share Posted May 7, 2009 Jesus Christ! That's like the worst reason to go for med Surely to God the poster was joking. Link to comment Share on other sites More sharing options...
Tango Charlie Posted May 7, 2009 Report Share Posted May 7, 2009 Chicks, money, power, and chicks. Link to comment Share on other sites More sharing options...
n00b Posted May 7, 2009 Report Share Posted May 7, 2009 for ian wong Link to comment Share on other sites More sharing options...
jdai Posted May 7, 2009 Report Share Posted May 7, 2009 Ok serious answer, since I'm waiting for my chicken strips to finish baking in the oven. --------------------------- I may be the most unmotivated person that got into med school, even if I said in the other thread that I got in after trying 7 times, which seems to say that I was very motivated. I used to be enthusiastic about med when I was younger and naive. I remember reading many things medicine related, from an awesome comic book about medicine being my favorite comic, to telling everyone I want to be a doctor, to writing a report in elementary school about the "Brain" when given the choice to write about anything. It was really funny thinking back. I was so curious about the human body and I wanted to know how it worked. Sometime during high school, I lost my motivation. Maybe it's growing up, maybe it's bitterness towards life (lol EMO), maybe it's a better knowledge of how the world and medicine works, or maybe it's the people I hung out with (read: slackers). I stopped caring. During undergrad, I kept trying to maintain my grades because I still wanted to go the medicine route, though not sure why; maybe I was just going through the motions that expectations of others has set out for me. A few "weeder" biochem courses swiftly came along and kicked my ass. I started to doubt that I have the grades to get into med, though foolishly continued to take further biochem courses that I don't like and getting ****tier and ****tier marks because that was the "status quo" for premeds. In hindsight, I should've just been a chem major since I absolutely loved chemistry, and I also got much better marks in chem classes. Graduation came around, and I found myself with a BSc. in General Biology (I wised up in 4th year and dropped biochem major like it was hot), but not accepted into med school. Stared blankly into space for the next 6 months because I didn't know what else to do, and then decided to "not waste any time" and applied for grad school. It was clinical research, but also a lot of basic science involved. I've done volunteer work in a lab running agarose gels and PCRs during a summer in undergrad, so I knew I absolutely hated research. Yet... out of expectations of my parents and my lack of motivation in anything else (including finding a job with my ****ty BSc.), I went through the motions of grad school and research for the next 3.5 years. Thinking back, there was NO fond memories (aside people I met), I abhorred the work, and I barely finished an MSc. after wasting a lot of time and my supervisor's money. My supervisor was not quite happy with me (so much for good references lol), though he was a nice guy and tolerated me, and I did so bad on my thesis defense (I didn't know **** lol) I was surprised they passed me even after I got ****ty feedback for not knowing my stuff after 3.5 years. Ahh... but the loopholes of a graduate degree is such that they rarely fail people on their thesis defense. With MSc. certificate in hand, I stood yet again on the road of life, staring blankly, not knowing what to do, and not really interested in what I can do with my qualifications. Med school again didn't accept me, and teaching didn't attract me (I've tutored before, I sucked so bad I put myself to sleep), and research, even if it paid well, is not my thing after 3.5 years of agony. I took a year off to play games, bum around the house, telling my parents "yeah yeah I'm looking for a job", did some volunteer work, and pretty much wasted away. Applied one last time for med school. I got accepted. Link to comment Share on other sites More sharing options...
jdai Posted May 7, 2009 Report Share Posted May 7, 2009 <Part 2> Honestly, to this day I'm still not sure why I'm in med. I didn't know what to expect before, and I still don't know what to expect now, even as I'm about to go into clerkship years. I can't say I hate med school; so far it's been more interesting than everything I did in undergrad/grad school, but clerkship is the "real" part of med school, and I'm not there yet. The stress, responsibilities, and long hours alone may break it for me likewise many med students. Though I still lack motivation (the fire of the curiosity of childhood will never return), I don't find myself hating the material or the interaction with patients. I'm holding onto that little nugget of realization as hopefully that I actually "like" medicine. If I can maintain that feeling (if "hmm I don't hate this" is considered a feeling) all the way until I retire, I think I may do alright. Definitely, I'm not your stereotypical med student. And since I'm so unmotivated for anything in life, why med? Assuming everything is all equally uninteresting, med does offer a decent career, and depending on the specialty, a lot of flexibility as well. I'm hoping to be a family doc that will one day run my own clinic, interact with a group of people I know and have a rapport with, and work at my own hours so I can pursue other interests in my spare time. Basically, be my own boss with the security and demand that comes with being a doctor. ------------------ TL; DR I once loved the thought of being a doctor, but then teenage came along and I got emo and I didn't like anything in the world anymore. Spent the next 10 years in a daze and now I'm in med. I guess it's a good job. I hope it is. My real and only passion this life? Being a mangaka (translation: japanese comic book author). LOLZ. Link to comment Share on other sites More sharing options...
n00b Posted May 8, 2009 Report Share Posted May 8, 2009 Hahahaha I love the tl;dr summary. Link to comment Share on other sites More sharing options...
bj89 Posted May 8, 2009 Report Share Posted May 8, 2009 <Part 2> Honestly, to this day I'm still not sure why I'm in med. I didn't know what to expect before, and I still don't know what to expect now, even as I'm about to go into clerkship years. I can't say I hate med school; so far it's been more interesting than everything I did in undergrad/grad school, but clerkship is the "real" part of med school, and I'm not there yet. The stress, responsibilities, and long hours alone may break it for me likewise many med students. Though I still lack motivation (the fire of the curiosity of childhood will never return), I don't find myself hating the material or the interaction with patients. I'm holding onto that little nugget of realization as hopefully that I actually "like" medicine. If I can maintain that feeling (if "hmm I don't hate this" is considered a feeling) all the way until I retire, I think I may do alright. Definitely, I'm not your stereotypical med student. And since I'm so unmotivated for anything in life, why med? Assuming everything is all equally uninteresting, med does offer a decent career, and depending on the specialty, a lot of flexibility as well. I'm hoping to be a family doc that will one day run my own clinic, interact with a group of people I know and have a rapport with, and work at my own hours so I can pursue other interests in my spare time. Basically, be my own boss with the security and demand that comes with being a doctor. ------------------ TL; DR I once loved the thought of being a doctor, but then teenage came along and I got emo and I didn't like anything in the world anymore. Spent the next 10 years in a daze and now I'm in med. I guess it's a good job. I hope it is. My real and only passion this life? Being a mangaka (translation: japanese comic book author). LOLZ. ur weird... Link to comment Share on other sites More sharing options...
laserlipo Posted May 11, 2009 Report Share Posted May 11, 2009 Hi all... I just want serve the public while serving i am also able to get respect and money from this profession so i want to be a doctor. Link to comment Share on other sites More sharing options...
Wut? Posted May 11, 2009 Report Share Posted May 11, 2009 Hi all... I just want serve the public while serving i am also able to get respect and money from this profession so i want to be a doctor. The respect and money that comes from doing, say, laser liposuction? Link to comment Share on other sites More sharing options...
n00b Posted May 11, 2009 Report Share Posted May 11, 2009 there is respect and money in that Link to comment Share on other sites More sharing options...
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