Solution-Cancer in immunocompromised individuals | Homework Helpers

Question 1: EMT in Invasion/Metastasis?

Our text emphasized epithelial-mesenchymal transition (EMT) as a major driver for invasion and metastasis. Though many researchers in the cancer field have adopted this hypothesis, skepticism remains, especially amongst tumor pathologists. EMT, though a fitting and sound explanation for the invasion-metastasis cascade, is difficult to observe since mesenchymal cells in vivo resemble populations normally found within the stroma. Yet, a search for EMT and cancer on Pubmed will yield thousands of entries within the last decade. Is EMT the key to understanding and potentially blocking metastasis, or do too many questions remain unanswered?

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In aIDition to the perspective presented in the text, read the articles by Tarin and Thompson, and argue whether or not you think EMT is responsible for invasion and/or metastasis of tumors.

Question 2: Tumor Dormancy – What triggers the switch?

The mechanisms that “trigger” micrometastases to develop into macrometastases (which can be clinically detected) are still poorly understood. However, elucidating these pathways could offer valuable insights into the long term treatment of cancer patients. In this Unit we learned about the possible (and likely cooperative) role of intracellular genetic changes and the immune system in this process. Interestingly, the efficiency of this process is believed to be very low (indeed, many patients exhibit micrometastases that never develop into full blown clinical metastases).

Argue which mechanism has a strongerinfluence on the outcome of colonization. What do you think is the main driver leading to the development of macrometastases from micrometastases?

Question 3: Cancer in Immunocompromised Individuals

Evidence that the human immune system can protect us from cancer (at least to an extent) is exemplified by the increased incidence of cancer in immunocompromised individuals. This is a fairly recent observation due to 1) the increased population of individuals receiving organ transplants (who often take immunosuppressive drugs to prevent rejection for extended periods of time), and 2) the increased longevity of populations infected with HIV. Based on your understanding of the role the immune system plays in the elimination or suppression of neoplastic cells, discuss one reason why immune compromised individuals develop higher rates of cancer. Be specific (i.e. differentiate between virally and non-virally induced cancers). Keep in mind that this is an ongoing discussion, please do not try to cover everything in one post

Why do immunocompromised individuals have a much higher incidence of cancer (be specific)?

Question 4: Write your own

• Explore the invasion-metastasis cascade and discuss relevant molecular pathways hypothesized to control this cascade such as epithelial-mesenchymal transition.
• Evaluate the role the innate and adaptive immune system in controlling cancer formation and progression.
• Compare and contrast the tumor promoting and inhibitory capabilities of the immune system.
• Discuss immunotherapies for cancer treatment and evaluate the benefits and challenges surrounding these treatment strategies.

Answered:-

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Epithelial-Melancholy Transition (EMT) is a well-known phenomenon which helps the epithelial cells to lose their characteristics such as adhesion with cell, cellular polarity, cell shape plasticity and becomes migratory and invasive in characteristic and finally becomes melancholy stem cells. According to some of the reported literature’s (Yang and Weinberg 2008, Yadi and Binhua 2009) it is absolutely correct to state that EMT is the key to understand metastasis because the initiation of metastasis indeed involves invasion process.Spanning to the information widely available in literature it can be understood that EMT is one of the important requirement for the process of tumor invasion and metastasis. On the contrary, according to other literature (Tarin 2005; Thompson and Newgreen 2005) suggests that such phenomenon do exists in the physiology but promising evidences have not been found in the in-vivo system. Despite of this, several other literature also proposes new models for this skepticism concept (Tsuji et al 2009). It was well understood that once the primary tumor formation is accomplished, the cell lines lose the property of adhesion between cell-cell and come out of the membrane with invasive property to enter into the blood stream.

It is also correct to state that EMT is also the key for potentially blocking the metastasis because EMT converses the resistance phenomenon to the premature/before-time senescence induced by oncogene. This is the major reason why the test for metastatic spread in cancer is used to be confirmed using the EMT test. Also it was reported that the transgenic mice were found to show dramatic reduction in metastasis where melancholy-specific promoter drove suicide construct, consistent with EMT important for ablation of metastatic cells.

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