Drug Discovery From Bench side to Bedside Assignment Sample
AN INVESTIGATION INTO LETHAL ISCHAEMIA / REPERFUSION INJURY AND ANTI-APOPTOTIC THERAPIES IN THE HUMAN MYOCARDIUM:
Background:
Description of diffuse large B-cell lymphoma: Diffuse large B-cell lymphoma is the blood cancer that is occurred into the white blood cell. White blood cell is the essential part of human body as the blood cell helps to increase the immunity power of the body. Diffuse large B-cell lymphoma is the one type of cancer that is occurred into white blood cell and it is called lymphocytes. Initially, different types of gland are occurred in neck, groin, armpits, and another parts of the body that impacts on the immune system of the body. The swelling is painless and spread very quickly. Within the few weeks the disease spread very rapidly and spread through different parts of the body. B-cell lymphoma is beginning within the lymph node and gradually spread through the other parts of immune system. So, initially treatment is necessary to cure the disease.
Current treatment option of DLBCL in the clinic: Diffuse large B-cell grows very quickly, and the only treatment of the disease is that chemotherapy. By the chemotherapy, glands are treated and remove the part from the body. Mainly, four types of medicines are used for the treatment of diffuse large B-cell such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), plus the monoclonal antibody rituximab (Rituxan). Combine of radiation and immunotherapy is used for the treatment of diffuse large B-cell. Besides the chemotherapy, radiation is used for the treatment of diffuse large B-cell (Li et al., 2018).
Role of constitutive IKKβ/NF-κB activation in DLBCL: diffuse large B-cell lymphoma has a high binding affinity of NF-κB DNA, constitutive IκB kinase (IKK) activity, and rapid IκBα degradation. For the development of normal B-cell, IKKβ/NF-κB activation is critical for human body. Heterodimers of IKKβ/NF-κB participate in different stages of B-cell differentiation and activation. NF-κB target genes encode to the immune response and regulates of cellular proliferation and apoptosis. As a result, express the target gene varies and NF-κB became activated.
Benefits and limitations of targeting the NF-κB pathway in cancer: NF-κB regulates the inflammatory response and mediating the induction of various inflammatory genes in innate immune cell. The function of NF-κB is to regulate the activation in B-cell, differentiation, and effector function of inflammatory T cells. Stimulation of NF-κB pathway promotes apoptosis and as a result, cancer is occurred in white blood cell. IκB proteins are degraded and activate the NF-κB. By the process of ubiquitination IKB protein is modified and by phosphorylation the protein is degraded and activate NF-κB pathway that causes cancer (Liu and Barta, 2019).
Potential of Gadd45β-targeting agents in cancer: NF-κB effector molecule activate the myeloid-intrinsic mechanism. Gadd45β restrict the tumor containing inflammation and trafficking of T-cell into tumor. Activation of proinflammatory tumor-associated macrophages (TAM) is inhibited by Gadd45β in myeloid cells. Gadd45β helps to overcome the immunosuppression. Gadd45β is the therapeutic target for the treatment of diffuse large B-cell lymphoma. That occurred to death a rapid cell growth. So, Gadd45β-targeting agents are used to treat for cancer.
Rationale and purpose:
Diffuse large B-cell lymphoma is cancer in white blood cell that occurs into the white blood cell. For the treatment of white B-cell lymphoma cancer chemotherapy is essential and besides that radiation is used for the treatment of blood cancer. In the clinic mainly four types of medicines are used such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), plus the monoclonal antibody rituximab (Rituxan). The purpose of the chemotherapy is that to kill the rapid cell growth that causes cancer. NF-κB effector is responsible to activate the cancer cell and it cause rapid cell growth in cell. For the treatment of cancer, Gadd45β targeting molecule is used for the treatment white blood cell cancer (Schuster et al., 2019).
Fig 1: Pathway of NF-κB survival with Gadd45β inhibitor.
By the pathway of NF-κB survival pathway with Gadd45β inhibitor, it is shown that IkB protein is degraded and activate the NF-κB protein that causes cancer and as a result reduce the immunity power of the human body and in the different parts of human body glands are formed such as neck, armpit, and other parts of the body. So, chemotherapy is needed for the treatment of cancer and Gadd45β inhibitor is used as the molecule of chemotherapy target. To reduce the inflammation of the human body chemotherapy and radiation is used. NK cell effect to the T-cell and causes inflammation so, the glands are formed in the different parts of the body. Gadd45 beta target molecule is used as chemotherapy that inhibits the rapid cell growth in the human body (Schmitz et al., 2018).
In the clinical, chemotherapy and radiation is used to kill the rapid cell growth in white cell blood. So, chemotherapy has a significant role to kill the rapid cell growth that helps to recover the immune response. By the chemical reaction, NF-kB protein function is activated in the white blood cell that increases the function oncogenic mutation and caused cancer. As a result, the molecule controls the cell function, cell division and cell death. So, rapid growth of cell or rapid death of cell causes cancer in the human body. For the treatment of cancer, Gadd45 beta target molecule is used that inhibits the function of NF-kB protein and helps to increase the immune system of human body. By the process of chemotherapy non-Hodgkin lymphoma use the anti-cancer drug that helps to destroy the cells which are responsible for cancer. After applying the anti-cancer drugs, it circulates inti the bloodstream of the body. As a result, these drugs distributed into all parts of the human body and reach to the effected part of the body that helps to destroy the rapid growth of cell. The sign of response in chemotherapy is that reduce the size of lymph nodes in the human body, and it is observed by externally. The blood test also helps to find out the level of protein molecule that is responsible for cancer (Chapuy et al., 2018). There is the only to treatment of cancer is that chemotherapy and radiation that helps to reduce the rapid cell growth in the human body. The aim of chemotherapy is that:
- Reduce the lymph nodes in the human body that is the sign to effect of chemotherapy and actively act into the body.
- The purpose of chemotherapy is to reduce the action of NF-kB protein that is responsible to cause diffuse large white blood cell lymphoma.
- The purpose of chemotherapy for diffuse large white blood cell lymphoma is that increase the immune system of human body that helps to control cell function, cell growth, and cell division.
Experimental plan:
cancer is deadly disease in the human body that has a critical impact in the human immune system. The diffuse large B-cell lymphoma is one type cancer that is occurred into the white blood cell. Initial treatment of diffuse large B-cell lymphoma can be curable and after the biopsy the part of the infected portion cut then use chemotherapy for the treatment of cancer. The initial sign of the disease is that form different types of lymph nodes at different parts of the human body such as armpits, neck, and other parts of the human body. So, by the experiment of size and condition of lymph node it is decided that the stage of cancer. Mainly these glands are painless and spread rapidly into the human body. So, initial experiment is needed to identify the stage of diffuse large B-cell lymphoma (Steen et al., 2021). Some of the cases, internal lymph nodes are not founded from external experiment so, X-ray and CT scan is essential to experiment the stage of cancer. By the experiment find out the size and others function of lymph nodes that helps to identify the stage of cancer. Besides that, blood test is performed by physician to experiment the disease. By the blood test the level and percentage of protein is calculated that helps to identify the stage and condition of the diseases. The high protein level of NF-kB is effective to cause the disease of diffuse large B-cell lymphoma. The function of organisms is determined by blood test so, it helps to find out the activity of other organisms that is needed to treatment for the disease. The tumor marker is used for diagnosis of diffuse large B-cell lymphoma. The presence of NF-kB is determined the disease of lymphoma (Kurtz et al., 2018).
There are different types of experimental plan to identify the disease of diffuse large B-cell lymphoma. Mainly blood test, count of cell, and test for tumor marker is used to identify the disease. Cell count helps to find out the rate of cell death or cell growth in the human body and it helps to identify the disease of cancer. Lymph node is the basic experiment of diffuse large B-cell lymphoma. And the presence of NF-kB protein identifies the disease of diffuse large B-cell lymphoma. Cancer reduces the immune system of the human body. So, reduction of immune response in the human body determines the disease of diffuse large B-cell lymphoma.
From the initial stage of the disease, treatment is essential that helps to reduce the chance to spread into the other parts of human body. Diffuse large B-cell lymphoma is one of the common types of non-Hodgkin lymphoma. The untreated lymphoma is fatal for human body. The basic experimental symptoms of the disease are that painless swelling and it spread into the different parts of the human body such as immune system, spleen, bone marrow and other parts of the body. Chemotherapy and radiotherapy are the process for treatment of diffuse large B-cell lymphoma. By the complete response, eth tumor is disappeared, and the patient is recovering from previous condition. The partial response is that the percentage and size of tumor is decreased, and stable condition is that the percentage and size of tumor is not increased or decreased. The progressed response is that rapidly grow the percentage and size of the tumor (Pasqualucci and Dalla-Favera, 2018).
Significance:
The size and number of tumors is the basic symptoms of diffuse large B-cell lymphoma. By the experiment, the stage of the disease is determined, and it helps to identify the condition of cancer.
Blood test to cell count: The blood test is done to determine the total cell count of the human body. As the increasing cell count helps to find out the rapid cell growth in blood and the decreasing cell count determine the cancer is caused in the human body. As a result, the physician can apply the treatment to recover from the disease.
Blood test to determine the function of other organisms: The blood test is done to determine the function of other organisms that helps to find out the function of organism. The immune system of the human body is decreased by cancer so, functions of different parts are not activated, and it is the symptoms of initial stage of diffuse large B-cell lymphoma.
Blood test to determine the presence of tumor marker: In the human body, tumor marker is present in the condition of cancer. So, blood test is essential to identify the presence of tumor marker. If the tumor marker is present in blood it is the symptom of cancer. The treatment should be started to recover from the disease. So, tumor marker can indicate the presence of cancer in the human body (Younes et al., 2019).
Swelling: The basic symptoms of diffuse large B-cell lymphoma is that swelling in different parts of the human body. These swelling is painless and spread in the human body rapidly. So, treatment should be started from the initial stage of the disease.
Chemotherapy and radiotherapy are the process for treatment of diffuse large B-cell lymphoma. Using chemotherapy reduce the level of cancer responsible protein marker and help to recover. So, from the initial stage cancer treatment is essential and recover the disease.
Reference:
Chapuy, B., Stewart, C., Dunford, A.J., Kim, J., Kamburov, A., Redd, R.A., Lawrence, M.S., Roemer, M.G., Li, A.J., Ziepert, M. and Staiger, A.M., 2018. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nature medicine, 24(5), pp.679-690.
Kurtz, D.M., Scherer, F., Jin, M.C., Soo, J., Craig, A.F., Esfahani, M.S., Chabon, J.J., Stehr, H., Liu, C.L., Tibshirani, R. and Maeda, L.S., 2018. Circulating tumor DNA measurements as early outcome predictors in diffuse large B-cell lymphoma. Journal of Clinical Oncology, 36(28), p.2845.
Li, S., Young, K.H. and Medeiros, L.J., 2018. Diffuse large B-cell lymphoma. Pathology, 50(1), pp.74-87.
Liu, Y. and Barta, S.K., 2019. Diffuse large B‐cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment. American journal of hematology, 94(5), pp.604-616.
Pasqualucci, L. and Dalla-Favera, R., 2018. Genetics of diffuse large B-cell lymphoma. Blood, The Journal of the American Society of Hematology, 131(21), pp.2307-2319.
Schmitz, R., Wright, G.W., Huang, D.W., Johnson, C.A., Phelan, J.D., Wang, J.Q., Roulland, S., Kasbekar, M., Young, R.M., Shaffer, A.L. and Hodson, D.J., 2018. Genetics and pathogenesis of diffuse large B-cell lymphoma. New England Journal of Medicine, 378(15), pp.1396-1407.
Schuster, S.J., Bishop, M.R., Tam, C.S., Waller, E.K., Borchmann, P., McGuirk, J.P., Jäger, U., Jaglowski, S., Andreadis, C., Westin, J.R. and Fleury, I., 2019. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. New England Journal of Medicine, 380(1), pp.45-56.
Younes, A., Sehn, L.H., Johnson, P., Zinzani, P.L., Hong, X., Zhu, J., Patti, C., Belada, D., Samoilova, O., Suh, C. and Leppä, S., 2019. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non–germinal center B-cell diffuse large B-cell lymphoma. Journal of clinical oncology, 37(15), p.1285.
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