Molecular Cell Biology A Review

Question: Discuss about the Article for Molecular Cell Biology for A Review. Answer: Review 1 The diagrammatic explanation of role played by Nitric oxide and cGMPA in muscle activation worked well in this presentation. I liked the way the whole mechanism was presented by stating all the mechanism step by step and systematically. I think the topic was well organized starting from the discovery of nitric oxide by three different scientists independently with the famous Furschgott Sandwich Experiment and then moving to explaining the main mechanism behind muscle relaxation. It clearly states how each scientist contributed to the understanding of its role. I learned the relation between NO and cGMP and how its activation leads to muscle reaction. However I would like to know more about each role of Calcium ions as this part was missing in the presentation. The physiological role and effect on each system were clearly stated in the presentation starting from L-arginine to formation cGMP and then its role in the phosphorylation of protein kinase G. I wished the writer could have pr esented a more clear illustrative diagram in the slide for endothelial role. Nitric Oxide synthase can target protein in proximity due to the phosphorylation of protein kinase G[1]. Myosin phosphatase plays the role in smooth muscle relaxation and it also explained another role like platelet inhibition and change in gene expression[2]. However, the presentation did not drift away from its purpose and concentrated mainly on an endothelial function related to NO. The biological mechanism of NO and cGMP was explained effectively in endothelial and smooth muscle cells. Reporting future research about NO was also a good way to end the presentations, however I would like to have more clarification regarding role of Yervoy as NSAID drugs. Positive comment: I got a good idea about different isoforms of Nitric Oxide synthase and their various roles in the body. Critical comment: Mechanism of muscle relaxation was effectively stated however the role of Calcium ions in the pathway was left behind. Question: Several studies have shown that there is a controversy regarding the lack of relaxation of uterine muscles to NO and cGMP. So what could be the reason behind it? Review 2 The promising role of monoclonal antibody therapy in targeting immune cells particularly tumor cells and treat advanced melanoma was well-explained in this slide presentation. I liked beginning of the presentation smartly starting with teaching cancer immunology as this will the basis to proceed further and gives detailed information. The role of the immune system is essential as Immunotherapy trains the immune systems to fight disease by boosting immune systems or train it to attack cancer cells specifically[3]. The limitation of the immune system was rightly stated as sometimes it fails to recognize cancer cells. Even it can recognize the cells, but the response is not strong enough to destroy cancerous cells. It states that T cell is the primary target of immunotherapy. As tumor cell has a mechanism to evade immune response, I was impressed with the information about the action regarding overcoming immune escape mechanism. I wished if the presentation had more citations related to specific information. It then brought to the forefront, CTLA4, a member of immunoglobulin superfamily expressed by T-cells and transmits inhibitory signals to T-cells. The mechanism of turning off of serotoxic reaction and survival of cancer cells given at the same time it also explained the role of humanized monoclonal antibody in targeting the antigen cells. Positive comment: The Lpilimumab survival map was well organized which demonstrated the survival rate in a precise way. I liked the development phase of Yervoy or Lpilimubab as it explained every phase of its development and complications[4]. Critical comment: The reasons for approval of Yervoy drug were good, but there is doubt regarding the continuing of therapy after response seen in some blood cancer patients. Question: I would like clarification regarding whether immunotherapy is a long-lasting solution to treat cancer? Reference Dippold, Rachael P., and Steven A. Fisher. "Myosin phosphatase isoforms as determinants of smooth muscle contractile function and calcium sensitivity of force production."Microcirculation21.3 (2014): 239-248 Frstermann, Ulrich, and William C. Sessa. "Nitric oxide synthases: regulation and function."European heart journal33.7 (2012): 829-837 Maio, Michele, et al. "Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial."Journal of Clinical Oncology(2015): JCO-2014 Pizzola, Christopher, S. M. Rizvi, and M. Joshi. "Evolving Role of Immunotherapy in Prostate Cancer."Current molecular pharmacology(2015). [1] Frstermann, Ulrich, and William C. Sessa. "Nitric oxide synthases: regulation and function."European heart journal33.7 (2012): 829-837 [2] Dippold, Rachael P., and Steven A. Fisher. "Myosin phosphatase isoforms as determinants of smooth muscle contractile function and calcium sensitivity of force production."Microcirculation21.3 (2014): 239-248 [3] Pizzola, Christopher, S. M. Rizvi, and M. Joshi. "Evolving Role of Immunotherapy in Prostate Cancer."Current molecular pharmacology(2015). [4] Maio, Michele, et al. "Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial."Journal of Clinical Oncology(2015): JCO-2014