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group_2_presentation_3_-_cancer [2020/03/26 12:46]
gandhr11
group_2_presentation_3_-_cancer [2020/03/26 22:36] (current)
gandhr11 [What did the study do?]
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 {{::​cancer.pptx|}} {{::​cancer.pptx|}}
  
-====== Cancer ======+====== Cancer: Rare and Recent======
  
-{{ ::​cancerg2.png?​direct&​300 |}} 
  
 ==== What is cancer? ==== ==== What is cancer? ====
  
 +{{youtube>​fQwar_-QdiQ?​medium | center}} ​
  
 Cancer is the generic term that is used to describe a large group of diseases that can affect any part of the body (“Cancer”,​ 2018). A defining feature of cancer is the rapid production of abnormal cells that grow beyond their normal boundaries (“Cancer”,​ 2018). While a normal cell would mature into specialized cells with specific functions, cancer cells do not; they are less specialized than normal cells (Nall, 2020). One reason cancer cells can divide without stopping is due to its ability to ignore signals that indicate they should stop dividing or begin a process known as programmed cell death - apoptosis, to get rid of unneeded cells (Nall, 2020). Under normal circumstances,​ human cells grow and proliferate new cells as the body needs them; when the cells grow old or become damaged, they die and new cells take their place. However, in cancerous cells, the process is broken down and cells become increasingly abnormal as old or damaged cells survive when they should have gone through apoptosis (Nall, 2020). In addition, new cells continue to form when they are not needed. These extra cells will continue to divide without stopping, which may become tumors. ​ Cancer is the generic term that is used to describe a large group of diseases that can affect any part of the body (“Cancer”,​ 2018). A defining feature of cancer is the rapid production of abnormal cells that grow beyond their normal boundaries (“Cancer”,​ 2018). While a normal cell would mature into specialized cells with specific functions, cancer cells do not; they are less specialized than normal cells (Nall, 2020). One reason cancer cells can divide without stopping is due to its ability to ignore signals that indicate they should stop dividing or begin a process known as programmed cell death - apoptosis, to get rid of unneeded cells (Nall, 2020). Under normal circumstances,​ human cells grow and proliferate new cells as the body needs them; when the cells grow old or become damaged, they die and new cells take their place. However, in cancerous cells, the process is broken down and cells become increasingly abnormal as old or damaged cells survive when they should have gone through apoptosis (Nall, 2020). In addition, new cells continue to form when they are not needed. These extra cells will continue to divide without stopping, which may become tumors. ​
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   * Unexplained bleeding or bruising (“Cancer”,​ 2018)   * Unexplained bleeding or bruising (“Cancer”,​ 2018)
  
-====== Von-Hipple Lindau Disease ======+====== ​Rare Cancer: ​Von-Hipple Lindau Disease ​(VHL) ======
  
 The VHL syndrome is a hereditary condition, specifically an autosomal dominant genetic condition (Varshney et al., 2017). This suggests that the risk of developing and acquiring this disease is passed on from generation to generation within a family (Varshney et al., 2017). Even though the disease is genetic, there have been many patients who have no family history of the condition (Maher et al., 1995). Infact, about 20% of people with VHL do not have any family history of the condition (Maher et al., 1995). The cause of this is the mutation, or the alteration, of the VHL gene which can give the person an increased chance of developing different types of cancer and a range of symptoms that are discussed below (Mukhopadhyay et al., 2002). ​ The VHL syndrome is a hereditary condition, specifically an autosomal dominant genetic condition (Varshney et al., 2017). This suggests that the risk of developing and acquiring this disease is passed on from generation to generation within a family (Varshney et al., 2017). Even though the disease is genetic, there have been many patients who have no family history of the condition (Maher et al., 1995). Infact, about 20% of people with VHL do not have any family history of the condition (Maher et al., 1995). The cause of this is the mutation, or the alteration, of the VHL gene which can give the person an increased chance of developing different types of cancer and a range of symptoms that are discussed below (Mukhopadhyay et al., 2002). ​
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 Patients diagnosed with this disease also have an increased risk of developing cancers like clear cell renal cell carcinoma, also known as kidney cancer (Bader & Hsu, 2012). This condition is very common between VHL patients as the risk of development of kidney cancer in families with VHL is estimated to be about 40% (Poulsen et al., 2010). Patients diagnosed with this disease also have an increased risk of developing cancers like clear cell renal cell carcinoma, also known as kidney cancer (Bader & Hsu, 2012). This condition is very common between VHL patients as the risk of development of kidney cancer in families with VHL is estimated to be about 40% (Poulsen et al., 2010).
  
-==== VHL Symptoms ====+<WRAP right round box 30%>  
 +{{ :​vhl_organs_image.jpg?​direct&​300 |}} 
 +**Figure 3: VHL affects lots of organs and that is why it is so interesting and rare.** 
 +</​WRAP>​
  
 +==== VHL Symptoms ====
  
 One of the most common symptoms of VHL is hemangioblastomas,​ which are basically these benign tumors developing mostly in the spine and brain (Lonser et al., 2004). These tumors might be encapsulated with a fluid filled sac within them which can further form cysts within the organ they are located in (Lonser et al., 2004). These cysts then press upon nearby nerves or brain tissue eventually leading to secondary symptoms such as headaches, migraine, trouble balancing, and muscle weakness (Sakaguchi, 2012). Hemangioblastomas occurring near or in the eye can result in fluid leakage which poses serious implications on one’s vision and ability to move the pupil (Bader & Hsu, 2012). Early detection of the formation of tumors is key to maintaining healthy vision in case of tumors occurring near or in the eye (Bader & Hsu, 2012). Moreover, these tumors can also occur in the kidneys but they usually metastasize or are removed and reportedly are not associated with any type of symptoms (Mukhopadhyay et al., 2002). VHL can also cause a tumor to form in the inner ear which is referred to as an endolymphatic sac (Vortmeyer & Alomari, 2015). The formation of this tumor can lead to problems in balance when walking as well as issues with the tympanic membrane causing hearing loss (Vortmeyer & Alomari, 2015). Tumors in the livers and lungs can occur but are not considered problematic (Maher et al., 1995). One of the most common symptoms of VHL is hemangioblastomas,​ which are basically these benign tumors developing mostly in the spine and brain (Lonser et al., 2004). These tumors might be encapsulated with a fluid filled sac within them which can further form cysts within the organ they are located in (Lonser et al., 2004). These cysts then press upon nearby nerves or brain tissue eventually leading to secondary symptoms such as headaches, migraine, trouble balancing, and muscle weakness (Sakaguchi, 2012). Hemangioblastomas occurring near or in the eye can result in fluid leakage which poses serious implications on one’s vision and ability to move the pupil (Bader & Hsu, 2012). Early detection of the formation of tumors is key to maintaining healthy vision in case of tumors occurring near or in the eye (Bader & Hsu, 2012). Moreover, these tumors can also occur in the kidneys but they usually metastasize or are removed and reportedly are not associated with any type of symptoms (Mukhopadhyay et al., 2002). VHL can also cause a tumor to form in the inner ear which is referred to as an endolymphatic sac (Vortmeyer & Alomari, 2015). The formation of this tumor can lead to problems in balance when walking as well as issues with the tympanic membrane causing hearing loss (Vortmeyer & Alomari, 2015). Tumors in the livers and lungs can occur but are not considered problematic (Maher et al., 1995).
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 Hemangioblastomas,​ benign lesions that can occur in the eye, brain and spinal cord arise from new vascularized tissue and  usually benefit from growth hormones such as vascular endothelial growth factors (VEGF). Certain medications such as bevacizumab (Avastin) or ranibizumab (Lucentis) may serve as antiangiogenic agents that can benefit individuals experiencing hemangioblastoma related complications in the eye. These agents have shown to reduce discharge from a cyst and improve vision, while having no effect on the size of the lesion ​ (Davis, S. & Uwaydat, S., 2010). Hemangioblastomas,​ benign lesions that can occur in the eye, brain and spinal cord arise from new vascularized tissue and  usually benefit from growth hormones such as vascular endothelial growth factors (VEGF). Certain medications such as bevacizumab (Avastin) or ranibizumab (Lucentis) may serve as antiangiogenic agents that can benefit individuals experiencing hemangioblastoma related complications in the eye. These agents have shown to reduce discharge from a cyst and improve vision, while having no effect on the size of the lesion ​ (Davis, S. & Uwaydat, S., 2010).
  
 +====== Recent Advances in Cancer Treatment ======
 +
 +Stadtmauer, E. A., Fraietta, J. A., Davis, M. M., Cohen, A. D., Weber, K. L., Lancaster, E., … June, C. H. (2020). CRISPR-engineered T cells in patients with refractory cancer. Science,​ 367(6481). doi: 10.1126/​science.aba7365
 +
 +{{::​crispr-engineered_t_cells_in_patients_with_refractory_cancer.pdf|}}
 +
 +==== Background Information:​ Gene Editing ====
 +
 +Gene editing has been a revolutionary discovery for the field of science because it is an opportunity to correct DNA mutations. It is a method in which we can treat or eliminate countless human genetic disease. Gene editing has the ability to change the DNA of cells with single-base pair precision. Genetic material can be added, removed or altered at a particular location in the genome. A recent advance in gene editing is the discovery of CRISPR-Cas9,​ short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. 
 +
 +==== CRISPR-Cas9 ====
 +
 +
 +CRISPR-Cas9 is adapted by naturally occurring genome editing system that is used by bacteria when it detects viral DNA. When viral DNA is detected inside the bacteria, the bacteria creates two short RNA's, one of which is an exact match to a segment on the viral DNA. The two short RNAs go on to form a complex with Cas9 (a nuclease). A nuclease is an ezyme that can DNA. The matching RNA (also known as the guide RNA), finds its matching target within the viral DNA. Following the match, Cas9 cuts the target DNA which disables the virus.
 +
 +Continuous research with CRISPR-Cas9 made discoveries that later allowed for its use in test tubes and within the nucleus of a living cell as well. Once it is inside the nucleus, the CRISPR-Cas9 complex can lock onto the known short sequence (also known as PAM) and then using its molecular scissors it cuts the DNA. The cell will try and fix this damage, how ever the repair process is highly error prone, with leads to mutations. These mutations disable the gene. 
 +
 +Further research, allowed for the discovery that this mutated gene can be replaced with a healthy copy by just adding another piece of DNA which carries the desired sequence.  ​
 +
 +To best explain how CRISPR-Cas9 works an animation and video is optimal. Understanding CRISPR-Cas9 is an important aspect for the study being done. 
 +
 +{{youtube>​2pp17E4E-O8?​medium | center}}
 +
 +
 +==== What did the study do? ====
 +
 +The researchers began by collecting the patients T-cells from their blood. Following that, they used the CRISPR-Cas9 system to edit three genes (TRAC, TRBC, PD-1). TRAC and TRBC are the T-cell'​s natural receptors and they were removed and reprogrammed to express a synthetic T-cell receptor which would seek out and destroy tumors. The research article mentions that the transgenic TCR ( T-cell) Receptor has been shown to mis pair and/or compete for expression with the a and b chains of the endogenous/​original TCR. Mispairing of the therapeutic TCR a and b chains with endogenous a and b chains reduces therapeutic TCR cell surface expression and potentially generates self-reactive TCRs. The third edit removed PD-1, a natural checkpoint that sometimes blocks T cells from doing their job. Once the three genes are knocked out, a fourth genetic modification was accomplished using a lentivirus to insert the cancer-specific synthetic T cell receptor, which tells the edited T cells to target an antigen called NY-ESO-1. Previously published data show these cells typically survive for less than a week, but this new analysis shows the edited cells used in this study persisted, with the longest follow up at nine months.
 +
 +<WRAP center round box 50%> ​
 +{{ :​cancerstudy.png?​direct |}}
 +**Figure 4: Retrieved from the study referenced at the start of the section**
 +</​WRAP>​
 +  ​
 ====== Conclusion ====== ====== Conclusion ======
  
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