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Sunday, November 26

  1. page UV Exposure, Skin Type and Cancer edited ... UV Radiation The sun gives off energy in three main of wavelegnths: visible light, infrared l…
    ...
    UV Radiation
    The sun gives off energy in three main of wavelegnths: visible light, infrared light, and UV light. There are 3 types of UV radiation: UVA, UVB and UVC. The ozone layer protects the earth against most UV radiation. It does not protect against UVA and sometimes UVB can get passed it and reach the earth. The level of UV light depends on the time of year, day, and location. Levels are highest at noon in the summer in places close to the equator . Also, 95% of UV radiation on earth is from UVA light. UVA radiation penetrates deeper into the skin, reaching the dermis layer whereas UVB light penetrates into the epidermis . This damages the DNA of cells in the epidermis and dermis and that can lead to mutations which can lead to skin cancer. Even though the UVA light penetrates deeper, the UVB light is more mutagenic . Cells try to protect themselves from DNA damage from the UV rays by donating melanin from the melanocytes to keratinocytes . This is the process that makes you tan.
    winkwhite
    {http://www.skincancer.org/media/legacy/stories/UVA_UVB/uvradiation3.jpg}
    Skin Types
    ...
    Basal Cell Carcinoma (BCC)
    Basal Cell Carcinomas are another very common type of skin cancer. It battles SCC for the most common type of skin cancer. These tumors arise in the basal layer of the skin but do not penetrate it. Usually look like sores, patches of open skin, pink skin growth, shiny bumps, or scars. It is usually caused by limited intervals of intense UV exposure or cumulative exposure over longer periods of time. It is not really life threatening because it doesn't penetrate the basal layer. It rarely spreads to other parts of the body .
    PANCEAPLUS
    Exposure to UV Radiation
    Generally speaking, the idea is easy, the less exposure to UV radiation, the better. More UV exposure causes more DNA damage which makes a person more prone to cancer.This DNA damage is what provides the "crispy" tan that so many people strive for. The p53 protein is responsible for releasing melanocyte stimulating hormones when it senses any DNA damage to the skin from UV exposure.
    ...
    Protection from UV Radiation
    Ways to protect yourself from UV radiation include covering up in clothes so that you don't expose your skin, stay in the shade, wear sunscreen,wear a hat and UV blocking sunglasses. Contrary to popular belief, dark colored clothing protects more than light colored clothing. Loose fitted is better then tight fitted because it allows for a more space between the clothes and skin for the light to penetrate through.There are special kinds of clothes with UPF (ultraviolet protection factor) that you can buy which limit UV penetration through the fabric [41] . Sunscreen has SPF that can help protect against UV rays. For good protection, one should use sunscreen with an SPF of 15 or higher and it should be applied to the skin 10-15 minutes before exposure. Also, some sunscreens protect only against UVAs but others can protect against both. Some of the active ingredients form a protective film on the skin which absorb UV radiation before it can penetrate the skin and the others reflect UV light [42] . The important thing about sunscreen is that you need to continuously re-apply throughout the day. This should be about every 2 hours or after swimming or sweating [43] . Hats can be work for protection as well. The best kind of hats for protection are those that are tightly woven, so not straw hats. Also, they should have a rim to provide shade to your face, ears and neck. Sunglasses can also be worn to protect the eyes from the UV rays; they should block both UVA and UVB rays.
    วิงค์ไวท์
    Conclusions
    Exposure to UV rays can cause skin cancer. UVA and UVB can reach Earth and UVA is more common but UVB is more dangerous. The levels of this exposure can vary with skin type, geographic location and time. Different skin types have varying skin cancer risks; generally the whiter you are, the higher the risk. The darker you are, the more melanin in your skin which protects against UV rays by scattering the light or absorbing it. Melanoma is the most dangerous type of skin cancer and originates in the basal layer of the epidermis. Basal cell carcinoma is the most common form of skin cancer and it the least dangerous; it occurs in the basal layer but does not penetrate it. Squamous cell carcinoma occurs in the upper layers of the epidermis from cumulative sun exposure. UV rays can cause mutations in DNA and an example of this is a mutation in the p53 gene which when functioning normally, suppresses tumors. One of the worst ways to promote this is indoor tanning because it exposes the skin to higher levels of UV rays than plain sunlight. To protect yourself from UV rays and to lower your risk for cancer, cover your skin when exposed to sunlight, wear hats and sunglasses and most importantly wear sunscreen!
    (view changes)
    11:25 pm

Sunday, January 8

  1. page TP53 edited What is the TP53 gene? {TP53.jpg} Genetic Home Reference, See Reference. ... of chromosome …

    What is the TP53 gene?
    {TP53.jpg} Genetic Home Reference, See Reference.
    ...
    of chromosome 17,17 , shown in
    p53 deals with cells with damaged DNA by deciding the ultimate fates of these cells . p53 'evaluates' whether the DNA damage is capable of being repaired; if so, p53 forms tetramers bind to DNA and activate the transcription of genes that can repair the damaged DNA .However if the DNA is damaged beyond repair, p53 stops cells from replication and triggers the apoptosis of these cells .
    The function of p53 is not limited to the regulation of cells with damaged DNA . In fact, p53 is responsible for determining cell fate under conditions such as lack of nucleotides for replication, hypoxia, and blockage of transcription . The figure below illustrates the various functions of TP53 in its mediation of celluar stress response.
    (view changes)

Wednesday, November 2

  1. page Second Primary Cancers edited Purpose Traditional PurposeTraditional cancer therapies Introduction After the remission of…

    Purpose
    Traditional
    PurposeTraditional cancer therapies
    Introduction
    After the remission of a first primary cancer, new tumors may arise to bring the patient out of remission and back into routines of hospitals and painful treatments. When a new tumor arises it can be as a result of metastasis, recurrence, or a new occurrence of the disease, and the origin of these tumors to classify them in one of these categories can be determined through histopathology (Ostrovnaya). According to the Gale Encyclopedia of Medicine, histopathology is the “study of diseased tissues at a minute level.” Through examination of the new tumors at a microscopic level, the tumor can be characterized by a distinct pattern of mutations which can be used to trace its clonal origins and determine if the new tumor arose as the progeny of a single (or multiple) cell left as a remnant of the primary cancer after the patient had completed treatment (Ostrovnaya).
    (view changes)

Friday, September 23

  1. page The Role of DNMT3A in Acute Myeloid Leukemia  edited ... In our cancer project, we will be focusing on the role of DNMT3A gene mutation in the progress…
    ...
    In our cancer project, we will be focusing on the role of DNMT3A gene mutation in the progression of Acute Myeloid Leukemia. As these studies have been published recently in the past few months, we will be analyzing how this new data fits in with previous studies on the prevalence of cancer stem cells leading to development of AML cancer. Further research into the differentiation of pre-leukemic stem cells would improve treatment methods by targeting the root causes of AML.
    Introduction
    ...
    Acute Myeloid Leukemia
    Adult
    LeukemiaAdult Acute Myeloid
    ...

    Hematopoeitic Stem Cells
    Hematopoietic
    CellsHematopoietic Stem Cells
    (1) it can renew itself;
    (2) proliferate and differentiate to replenish all functional types of blood cells
    ...
    Studies have also revealed there to be two kinds of HSCs: (1) long-term stem cells that are capable of self-renewal, and (2) short-term progenitor or precursor cells
    that can proliferate but that cannot differentiate into more than one cell type (NIH, 2011). For example, a blood progenitor cell may only be able to make another red blood cell.
    DNMT3a
    DNMT3a
    DNMT3aDNMT3a is a
    ...
    al. 2010).
    Overview
    Over

    OverviewOver
    the past
    Research
    Pre-leukemic Ancestor Cells
    According
    CellsAccording to a
    {http://4.bp.blogspot.com/-oD3RgGD6xXE/U0YhXApHEOI/AAAAAAAAAY4/SXUWD6DCXT0/s1600/figure1b.png}
    Table 1. Frequency (%) of both mutated DNMT3A and NPM1c in isolated CD33+ AML blasts and T cells. A procedure called ddPCR (droplet digital PCR) was used to determine the mutant allele frequencies corresponding to the length of the bars in 17 patients with normal karotype AML. (Slush, Liran, Sasan Zandi, et al. 2014)
    ...
    Figure 2. DNMT3A mutant allele frequency in sorted cell populations isolated from diagnosis (0 months), early (3) and late (36) remission samples of patient no. 57 (Shlush, Liran, Sasan Zandi, et al. 2014)
    There is a significant increase in mutated DNMT3A allele frequency in most cell populations over time (Figure 2) . In addition, though not evident in the figure, a small proportion of CD33+ myeloid cells at late remission also contained both mutated DNMT3A and NPM1c found in diagnosis. This meant that somehow there had been a regrowth in the diagnostic leukemic clone or emergence of a new clone following an independent NPM1c mutation within the pool of pre-leukemic ancestral cells. This suggests that the mutated DNMT3A found in HSCs/MPPs at diagnosis was capable of multilineage differentiation that somehow evaded chemotherapy and gave rise to clones that presented themselves at remission, and could potentially serve as a “reservoir” for further evolution of these clonal cells that leads to relapse of the disease.
    DNMT3a Mutation Frequency
    Approximately
    FrequencyApproximately 26% of
    {Screen Shot 2014-05-18 at 10.38.20 AM.png}
    Figure 4. DNMT3a Mutations in 188 Patients with Acute Myeloid Leukemia. (Ley, Timothy J., et al, 2010)
    The most common mutation within mutations of DNMT3a is a missense at the R882 residue of the protein, either R882H or R882C. There are also less common nonsense, frameshift, and splice site mutations throughout the coding sequence. Finding a common mutation source suggests that there may be a common methylation pattern or similar cause of the mutated methyltransferase gene. However, studies so far have not found evidence that the effects of this one amino acid substitution are significant, as shown in the Kaplan-Meier curves in the next section.
    DNMT3a Mutation Survival
    Once
    SurvivalOnce a DNMT3a
    {Screen Shot 2014-05-11 at 10.54.22 PM.png}
    Figure 5. Overall Survival in AML patients with DNMT3a mutations. (Ley, Timothy J., et al, 2010)
    DNMT3a mutation presence is a more significant predictor of cancer fatality than any other mutation, and persists despite age, which is the largest factor in survival. It is also possible that the reasons for dramatically low survival in DNMT3a mutations may be partly due to those patients not yet having an effective targeted treatment for their type of leukemia.
    The R882H mutation would be expected to disrupt normal functioning of DNMT3a in affecting transcriptional regulation of genes. Each of the Kaplan-Meier estimates show a separate curve for patients specifically with a R882 DNMT3a mutation, since it is the most frequent. Based on this data, the R882 mutation only has a very slight, if any, difference in survival when compared to other DNMT3a mutations. Other studies on the R882 mutations disagree on whether the mutation type causes gain-of-function or loss-of-function for the methyltransferase, but it is likely that both occur at different densities of CpG sites (Schoofs, 2014). Holz-Schietinger provided evidence behind this idea by finding that there is a loss of methylation at clustered CpG islands, and hypermethylation at isolated CpG locations (Holz-Schietinger, 2014).
    Treatment Methods
    The
    MethodsThe current goal
    Age seems to play a significant role in whether the disease can be cured or go into remission. For patients under the age of 60, the combination of cytarabine and allogeneic hematopoietic cell transplantation (HCT) improves cure rates to 50% (Smith, et al. 2014). However, for individuals over the age of 60, the cure rate remains quite low. These elderly patients generally do not receive intensive chemotherapy in the first place, since the side effects outweigh their therapy benefits. The standard treatment of the anti-metabolite cytarabine, which inhibits DNA synthesis during the S phase of mitosis, also damages healthy cells with its high toxicity (Al-Ali, et al. 2014).
    .
    ...
    Overall survival was significantly better in the AZA-treated cohort compared with patients in the DEC-treated cohort (10.1 months vs. 6.9 months respectively; p = 0.007, Figure 6) and treatment with azacitidine resulted in a significantly longer time to death when compared with decitabine treatment. The most crucial aspect of the entire study, however, was that patients were not randomly assigned to treatment and administration schedules (i.e. dosing and adherence) for each therapy were not controlled.
    Analysis
    ...
    on HSC Differentiation
    Since
    DifferentiationSince the hematopoietic
    ...
    on AML Treatment
    Though
    TreatmentThough still undergoing
    ...
    of cytarabine.
    Conclusion
    DNMT3a

    ConclusionDNMT3a
    is a
    Sources
    Al-Ali, Haifa Kathrin, Nadja Jaekel, and Dietger Niederwieser. "The role of hypomethylating agents in the treatment of elderly patients with AML." Journal of Geriatric Oncology 5.1 (2014): 89-105. Journal of Geriatric Oncology. Web. 21 May 2014. <http://www.geriatriconcology.net/ article/S1879-4068(13)00086-6/fulltext>.
    (view changes)

Saturday, June 11

  1. page 2016 Cancer Projects edited Stephanie Li Carlos Medina Nikki Janssen Uma Palaniappan Sarah Craven Hannah Robin Daniel Ho…
    Stephanie Li
    Carlos Medina
    Nikki Janssen
    Uma Palaniappan
    Sarah Craven
    Hannah Robin
    Daniel Horvath
    Sarah Thomas
    Lauren Rice
    Jacy Rasnick

    Saira Ahuja
    Matthew Martini
    Paul Kozel
    Robert Kousnetsov
    Danielle Willkom
    Drew Del Toro
    Megan Kohn
    Saron Araya
    Emily Barker
    Ivan LiangSrivarchala Chandu
    Megan Ching
    Sarah Craven
    Mitchell Dang
    Mikael StovarskyDrew Del Toro
    Ethan Hazel
    Daniel Horvath
    Nikki Janssen

    Amanda Khoo
    Sonette Steczina
    Srivarchala Chandu
    Emily Paton
    Megan Kohn
    Robert Kousnetsov
    Paul Kozel
    Stephanie Li
    Ivan Liang
    Matthew Martini
    Carlos Medina

    Mayron Mulugeta
    Lawrence Santos
    Onye Okolo
    Ethan Hazel
    Saron Araya
    Uma Palaniappan
    Emily Paton
    Jacy Rasnick
    Lauren Rice
    Hannah Robin
    Lawrence Santos
    Sonette Steczina
    Mikael Stovarsky
    Sarah Thomas
    Danielle Willkom

    (view changes)
    3:20 pm

Thursday, June 9

  1. page Stephanie Li edited ... Lucia Li’s phyllodes tumor was not diagnosed as malignant, and also had not metastasized. This…
    ...
    Lucia Li’s phyllodes tumor was not diagnosed as malignant, and also had not metastasized. This means that she needed no additional therapy (chemotherapies, radiation therapies, etc) besides the mastectomy, or removal of the whole breast. She fortunately received the surgery before her tumor had a chance to metastasize to the nearby lymph nodes, and therefore served as a great example for a victim of the false-negative curse that the ultrasound-guided biopsy is guilty of. Had the doctors used a method that would have diagnosed her tumor as a phyllodes tumor earlier on, she may not have needed a full mastectomy, and perhaps would have been find with just a lumpectomy. The most important and unfortunate fact was that her tumor was concluded to be a phyllodes tumor only after it was removed and sent to the Stanford and UCSF labs for further research. In the future, if ultrasound elastography could be used in a clinical setting and expand beyond the musculoskeletal regions, then perhaps phyllodes tumors and fibroadenomas would not be mistaken as one for the other so easily.
    Aperçu
    ...
    tumor and fibroadenomas, especially if only viewing them from one angle.
    -
    fibroadenomas on mammograms and ultrasounds, how they look the same on the surface, but are so different underneath.
    -
    -
    (view changes)
    7:02 pm
  2. page Srivarchala Chandu  edited I. Cancer ===== Ana Ana grew up ... blood-brain barrier. {Neuron.png} ===== {Neuron.pn…

    I. Cancer
    ===== AnaAna grew up
    ...
    blood-brain barrier.
    {Neuron.png}

    ===== {Neuron.png}
    Figure 1: Gilal cells
    =====
    Most cases
    ...
    the tumor .
    =====Ana
    .Ana did not
    ...
    Li-Fraumeni syndrome” .. But after
    {brainlobes.png} Figure 2: Lobes of the Brainplastic Astrocytoma . While among siblings this ratio was tripled indicating a higher chance of Anaplastic Astrocytoma, if Ana’s siblings were to have the same condition . This also means that Ana’s children, and siblings will have to be tested for astrocytomas.
    =====InIn Ana’s case,
    ...
    in the brain”.brain” .
    Unfortunately, the prognosis for this disease is dependent on where the tumor is located, and the age of the patient. Ana is 32 and her tumor is located her parietal lobe. The long term prognosis is that most patients will experience reemergence of the disease and will die from cancer. For Ana, this means that while she may have a strong chance of survival because, her tumor is in the parietal lobe of the brain and will eventually affect her sensation, perception and spatial perception, if it is left untreated.
    II. Molecular Markers
    ===== InIn order to
    ...
    to cancer.
    ===== {p53.png}

    {p53.png}
    Figure 3:
    ...
    certain functions.
    =====IDH1/2

    IDH1/2
    codes for
    These epigenetic changes will then lead to more changes in the way that the DNA is read and eventually what proteins are made.
    Our next gene is ATRX , which codes for a protein ATRX. When mutated this protein is involved in telomere lengthening . This is important because teleomeres, repeating sequences at the end of chromosomes, are shortened at the end of every replication cycle. So as the cancer cells grow and divide their telomeres get shorter, which means that their genetic information will eventually be damaged beyond repair. This will cause the cancer to grow and leads to more mutations. We see this in Ana’s case as her cancer cells have a loss of heterozygosity on chromosome 19. This means that her cells have lost an entire gene. With the mutation of ATRX there will be a lengthening of these telomeres, and so there will be replicative immortality, another hallmark of cancer. Replicative immortality is important because it means that the cell is able to grow and divide forever.
    =====While,While, the deletion
    ...
    being more agressive.agressive . Lastly, MGMT codescodes for a
    ...
    has a methylatedmethylated promoter that
    All of the genes that have been mutated are important to the growth and initiation of Ana’s cancer. These mutations have shown us that the functions of these proteins are extremely important to how Ana should be treated.
    III.Treatments
    After her diagnosis Ana is now in the hospital accompanied by her husband. She is worried about her kids, and scared that they will grow up without a mother just as she did. Her doctors come to visit her and go over the various options that she has based on her diagnosis. Surprised to hear she has a choice in her treatment, she is grateful for the information that the doctors have provided.
    =====AstrocytomasAstrocytomas are difficult
    ...
    can help.
    ===== Adjuvant

    Adjuvant
    treatment is
    Ana then would receive radiation as her adjuvant therapy. Radiation therapy is the use of highly concentrated radiation, like x rays, to kill cancer cells. This is helpful because it concentrates the radiation to a specific part of the body. But its side effects include fatigue, and a risk of developing another cancer.
    =====TheThe clinical trial
    ...
    triggers cell death.death . As discussed
    ...
    temozolomide treatment .This .This trial would
    Ana decided to signup for the clinical trial, but first she needed to get her resection surgery. While sitting in the ward she sees many people around her with similar brain tumors, and while she feels a sense of community, she sees that many are dying and new patients are coming in everyday. Her initial fear and stress return. But she is soon taken into get her cancer resected. The surgery goes well and when the pathology reports come back about her cancer, her doctors see that there are clean margins. This means that they have gotten the entire tumor and there is no cancer in the surrounding tissue. Unfortunately for Ana she cannot move her right arm, and has limited vision in her right eye. Her doctors tell her that she will need physical therapy. They are also worried about her ability to handle chemotherapy along with radiation. They believe that her quality of life will become more compromised, and want her to first recover from her surgery. But this also means that she cannot go through with the clinical trial. Her doctors reassure her that the drug will not help Ana as her tumor appears to have full been resected. But she will need to come back monthly for checkups, to make sure there is no recurrence.
    Fortunately for Ana she is able to regaining control of her arm and even her vision is slowly improving. Her cancer has not yet returned, but she is vigilant and goes to yearly checkups, frightful that the cancer will return. For now, she can take care of her children and is thankful for her life.
    Apercu:
    Brain Tumors do not discriminate. They affect people of all ages and only 34 percent of people who have brain tumors will survive for 5 years after their initial diagnosis. This is a daunting statistic, but as treatments and diagnosis gets better there is hope for people with this deadly disease.
    =
    Hurty, Arne. The Other Brain Cells. Stanford Medicine. By Bruce Goldman. Web.
    <http://sm.stanford.edu/archive/stanmed/2009fall/article6.html>.
    ...
    Hurty, Arne. The Other Brain Cells. Stanford Medicine. By Bruce Goldman. Web.
    <http://sm.stanford.edu/archive/stanmed/2009fall/article6.html>.
    =====
    Stupp, Roger, Michele Reni, Gemma Gatta, Elena Mazza, and Charles Vecht.
    "Anaplastic Astrocytoma in Adults." Critical Reviews in Oncology/Hematology 63.1 (2007): 72-80. Web. <http://www.croh-online.com/article/S1040-8428(07)00056-X/fulltext#section0035>.
    ...
    Hemminki, K., S. Tretli, J. H. Olsen, L. Tryggvadottir, E. Pukkala, J. Sundquist, and C.
    Granström. "Familial Risks in Nervous System Tumours: Joint Nordic Study." Br J Cancer British Journal of Cancer 102.12 (2010): 1786-790. Web. <http://cebp.aacrjournals.org/content/12/11/1137.long>.
    =====
    "Neuro-Oncology : How Our Patients Perform : Anaplastic Astrocytoma [AA]." University of California, Los Angeles Neuro-Oncology : How Our Patients Perform : Anaplastic Astrocytoma [AA].
    <http://neurooncology.ucla.edu/Performance/AnaplasticAstrocytoma.aspx>.
    Stupp, Roger, Michele Reni, Gemma Gatta, Elena Mazza, and Charles Vecht.
    "Anaplastic Astrocytoma in Adults." Critical Reviews in Oncology/Hematology 63.1 (2007): 72-80. Web. <http://www.croh-online.com/article/S1040-8428(07)00056-X/fulltext#section0035>.
    =====
    Brat, Daniel J., et al. "Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas." The New England journal of medicine 372.26 (2015): 2481-2498 <http://www.nejm.org/doi/full/10.1056/NEJMoa1402121#t=articleBackground>
    ===== =
    Ryan, Kevin M., Andrew C. Phillips, and Karen H. Vousden. "Regulation and function of the p53 tumor suppressor protein." Current opinion in cell biology 13.3 (2001): 332-337. <http://www.sciencedirect.com/science/article/pii/S0955067400002167>.
    "TP53." Genetics Home Reference. Web. 17 May 2016. <https://ghr.nlm.nih.gov/gene/TP53#location>.
    ...
    Ryan, Kevin M., et al.
    Ryan, Kevin M., et al.
    =====
    Waitkus, Matthew S., Bill H. Diplas, and Hai Yan. "Isocitrate dehydrogenase mutations in gliomas." Neuro-oncology 18.1 (2016): 16-26. http://neuro-oncology.oxfordjournals.org/content/18/1/16.full>.
    Waitkus, Matthew S., Bill H. Diplas, and Hai Yan. "Isocitrate dehydrogenase mutations in gliomas." Neuro-oncology 18.1 (2016): 16-26. http://neuro-oncology.oxfordjournals.org/content/18/1/16.full>.
    ...
    Rakheja, Dinesh et al. “The Emerging Role of D-2-Hydroxyglutarate as an Oncometabolite in Hematolymphoid and Central Nervous System Neoplasms.”Frontiers in Oncology 3 (2013): 169. PMC. Web.<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698461/>.
    Lovejoy, Courtney A., et al. "Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathway." PLoS Genet 8.7 (2012): e1002772. <http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1002772>.
    =====
    Jiang, Haihui, et al. "1p/19q codeletion and IDH1/2 mutation identified a subtype of anaplastic oligoastrocytomas with prognosis as favorable as anaplastic oligodendrogliomas." Neuro-oncology 15.6 (2013): 775-782. http://www.ncbi.nlm.nih.gov/pubmed/23486687>.
    Jiang, Haihui, et al. "1p/19q codeletion and IDH1/2 mutation identified a subtype of anaplastic oligoastrocytomas with prognosis as favorable as anaplastic oligodendrogliomas." Neuro-oncology 15.6 (2013): 775-782. http://www.ncbi.nlm.nih.gov/pubmed/23486687>.
    ...
    Jansen, Michael, Stephen Yip, and David N. Louis. "Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers." Lancet Neurol9 (2010): 717-26. <http://apps.elsevier.es/watermark/ctl_servlet?_f=10&pident_articulo=13187222&pident_usuario=0&pcontactid=&pident_revista=602&ty=44&accion=L&origen=zonadelectura&web=www.elsevier.es&lan=en&fichero=602v09n07a13187222pdf001.pdf>
    Jansen, Michael, Stephen Yip, and David N. Louis. "Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers." Lancet Neurol9 (2010): 717-26. <http://apps.elsevier.es/watermark/ctl_servlet?_f=10&pident_articulo=13187222&pident_usuario=0&pcontactid=&pident_revista=602&ty=44&accion=L&origen=zonadelectura&web=www.elsevier.es&lan=en&fichero=602v09n07a13187222pdf001.pdf>
    =====
    Stupp, Roger, et al. "Chemoradiotherapy in malignant glioma: standard of care and future directions." Journal of Clinical Oncology 25.26 (2007): 4127-4136. <http://jco.ascopubs.org/content/25/26/4127.abstract>
    =====
    Stupp, Roger, et al.
    Stupp, Roger, et al.
    =====
    Zhang, W., et al. "[Randomized controlled study of limited margins IMRT and
    temozolomide chemotherapy in patients with malignant glioma]." Zhonghua yi xue za zhi 95.31 (2015): 2522-2525. <http://www.ncbi.nlm.nih.gov/pubmed/26711384>.
    (view changes)
    6:47 pm
  3. page Srivarchala Chandu  edited I. Cancer Ana ===== Ana grew up ... Less than 20 15 years later, ... now a 38 32 year…

    I. Cancer
    Ana===== Ana grew up
    ...
    Less than 2015 years later,
    ...
    now a 3832 year old
    ...
    dealing with pain,headaches, and mood changes.swings. She does
    ...
    and worries constatnlyconstantly about her
    ...
    a brain tumor, specificallytumor. After a biopsy, she was given the diagnosis of a grade
    ...
    as Anaplastic Astrocytoma[i] (Figure 1). {Neuron.png}Astrocytoma. An astrocyte is a glial cell, in the brain, that supply the neuron with nutrients and support the endothelial cells at the blood-brain barrier.
    {Neuron.png}
    Figure 1: Gilal cells
    Most

    ===== Most
    cases of
    ...
    aggressive the tumor.
    Ana
    tumor .
    =====Ana
    did not
    ...
    Li-Fraumeni syndrome” [ii]. . But after genetic testing,testing of her tumor, the doctor
    ...
    of heterozygosity, or an entire gene, on chromosome 19ii.Chromosome 19 is where the “glioma tumor suppressor gene is located”, meaning19. This means that Ana has lost part of a loss in this gene would lead to unadulterated growthon one of the tumor [iii].her chromosomes . While Ana’s
    ...
    case, meaning that members of
    ...
    value that indicatedindicates the ratio
    ...
    of the Brain
    plastic Astrocytoma[iv].
    Brainplastic Astrocytoma . While among
    ...
    same condition iv. . This also
    ...
    for astrocytomas.
    In

    =====In
    Ana’s case,
    ...
    survival rates. About 25% of people who get diagnosed with this cancer will survive the first five years after daignosis . Anaplastic Astrocytoma
    ...
    it continues willto develop andit will grow into
    ...
    brain and bodybody, rather they
    ...
    in the brain”[ii].In fact, “metastases are typically linked with contamination during surgery” [ii]brain”.
    Unfortunately, the
    ...
    the patient. LongAna is 32 and her tumor is located her parietal lobe. The long term prognosis
    ...
    chance of survival,survival because, her tumor
    ...
    and spatial perception.perception, if it is left untreated.
    II. Molecular Markers
    In===== In order to
    ...
    molecular basis. ForAfter her biopsy, Ana's doctors have found that she has multiple mutations. In general, Anaplastic Astrocytomas, we can focus ontend to show mutations in four major genes that are mutated:genes: TP53, IDH1/2, ATRX [v]and and MGMT. Another
    ...
    deletion in the qone arm of
    ...
    to cancer.
    {p53.png}

    ===== {p53.png}
    Figure 3:
    ...
    or kill itself[vi].itself . Most of
    ...
    protein binds DNA[vii].DNA . This signals to us that the
    ...
    is important. P53p53 has many
    ...
    cancer. Figure 13 also shows
    ...
    repair itself [viii]. . In order to lead the cell to apoptosis
    ...
    death receptors pathway[ix].pathway . For our
    ...
    mitochondrial apoptotic pathwaypathway. If we
    ...
    to Figure 1,3, we can
    ...
    p53 starts a pathway that leads to the expression
    ...
    proteins like Bax. BaxBAX. BAX then triggers
    ...
    complex, Apaf-1/caspase-9 apoptosome[x].apoptosome . This protein
    ...
    death. So, then, if this
    ...
    is mutated then it can
    ...
    cancer, because it the p53 cannot kill cells that haverespond to DNA damage
    ...
    example, p21Waf1/Cip1, a protein inhibitor of the cell cycle, is a
    ...
    to this gene significantlyprotein diminishes its response to p53[xi].p53 . So even
    ...
    substrate is mutated.
    IDH1/2
    mutated, and does not respond to p53. This pathway is important because it allows our cells to kill themselves if it cannot be repaired. Without the use of this pathway, cells can contiue to grow even though they are dangerous to the body because they lack certain functions.
    =====IDH1/2
    codes for
    ...
    acid cycle. As Figure 4 shows us, IDH proteins
    ...
    NADP, to decarboxlyzeremove a carbon from isocitrate and
    ...
    α-ketoglutarate, this process produces NADPH [xii]. . In ourAna's cancer IDH1
    ...
    are mutated. Specifically theseThese proteins share
    ...
    they are gentetiacallygenetically very similar[xii].similar . The difference
    ...
    the cytosol and peroxisomes,of the cell, while IDH2
    ...
    of cellular functions, including glucose sensing, glutamine metabolism, lipogenesis, and regulation of cellular redox status” .functions." IDH1 has
    ...
    under stress conditions[xii].IDH2 has also does the same function, but uses a different mechanism.conditions . The most
    ...
    our cancer. If mutated, this protein can leadAlterations of these proteins impairs their normal ability of IDH1/2 to a deficiency of metabolismconvert isocitrate to α-ketoglutarate (αKG) and instead they convert αKG to D-2-hydroxyglutarate (2HG) .This increase in 2HG has shown to increase the brain, which would fuel our cancer’s need to use glycolysis. This switch from one typelevels of metabolismmethylation and epigenetic changes to another is an important hallmarkthe cell's DNA .
    These epigenetic changes will then lead to more changes
    in cancer, because it shows us how the cancer can get nutrients withoutway that the blood supply.
    Our
    DNA is read and eventually what proteins are made.
    Our
    next gene
    ...
    a protein ATRX that whenATRX. When mutated this protein is involved
    ...
    telomere lengthening [xiii]. . This is
    ...
    divide forever.
    While,

    =====While,
    the deletion
    ...
    different prognosis [xiv]. . Patients with this deletion, like Ana, will have a higher rate of reoccurrence, and leads to the cancer being more agressive. Lastly, MGMT codes codes for a
    ...
    a transfer methylasemethylase, and is involved
    ...
    repairing alkylating damage, like the damage [xv]. Thisthat is caused by certain chemotherapies . Because this protein is important because it is involved
    ...
    by chemotherapy, making the cancer immune chemotherapy.[xvi] Ifpatients with a mutation in this gene’s promoter is methylated then the protein will not be produced, and damage cannot be repaired [xvi]. With this protein inactive, researchmore sensitive to chemotherapy . In Ana's case, her cancer has a methylated promoter that inactivates the MGMT protein. Research has found
    ...
    repair themselves [xvi].All .
    All
    of the
    ...
    important to the survival of the cancer, and we can further see that they don’t necessarily have tohow Ana should be mutated themselves to lead to cancer.treated.
    III.Treatments
    After her diagnosis Ana is now in the hospital accompanied by her husband. She is worried about her kids, and scared that they will grow up without a mother just as she did. Her doctors come to visit her and go over the various options that she has based on her diagnosis. Surprised to hear she has a choice in her treatment, she is grateful for the information that the doctors have provided.
    Astrocytomas=====Astrocytomas are difficult
    ...
    are star-shaped (Figure1).(Figure 1). This means
    ...
    of the tumor[xvii].tumor . This will
    ...
    can help.
    Adjuvant

    ===== Adjuvant
    treatment is
    ...
    treatment of surgery[xvii].surgery . This is
    ...
    clinical trial [xvii] . . Clinical trials
    ...
    and aggressive tumorsi.tumors. Another option
    Ana then would receive radiation as her adjuvant therapy. Radiation therapy is the use of highly concentrated radiation, like x rays, to kill cancer cells. This is helpful because it concentrates the radiation to a specific part of the body. But its side effects include fatigue, and a risk of developing another cancer.
    The=====The clinical trial
    ...
    with radiation therapy[xviii].therapy . Temozolomide is
    ...
    triggers cell deathii.death. As discussed in the previous section, Ana has an epigenetic mutation in her MGMT protein. This means that she will be more sensitive to the temozolomide treatment .This trial would
    ...
    help her.
    So, Ana

    Ana
    decided to
    ...
    the clinical trail.trial. Her doctors
    ...
    to yearly checkups. Shecheckups, frightful that the cancer will return. For now, she can take
    Apercu:
    Brain Tumors do not discriminate. They affect people of all ages and only 34 percent of people who have brain tumors will survive for 5 years after their initial diagnosis. This is a daunting statistic, but as treatments and diagnosis gets better there is hope for people with this deadly disease.
    [i]Hurty,=
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    =====
    Brat,
    Daniel J.,
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    =====
    Ryan,
    Kevin M.,
    ...
    332-337. <http://www.sciencedirect.com/science/article/pii/S0955067400002167>.
    [ix] Ryan,

    "TP53." Genetics Home Reference. Web. 17 May 2016. <https://ghr.nlm.nih.gov/gene/TP53#location>.
    Ryan,
    Kevin M.,
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    [xi] Ryan,

    Ryan,
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    ...
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    Ryan, Kevin M., et al.
    Ryan, Kevin M., et al.
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    Waitkus,
    Matthew S.,
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    Waitkus, Matthew S., Bill H. Diplas, and Hai Yan. "Isocitrate dehydrogenase mutations in gliomas." Neuro-oncology 18.1 (2016): 16-26. http://neuro-oncology.oxfordjournals.org/content/18/1/16.full>.
    Waitkus, Matthew S., et al.
    Kalinina, Juliya, et al. "Detection of “oncometabolite” 2-hydroxyglutarate by magnetic resonance analysis as a biomarker of IDH1/2 mutations in glioma."J Mol Med 90 (2012): 1161-1171 <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147374/>.
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    Jiang,
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    [xv]Stupp,

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