Doctors on DNA, Cancer, Renal Failure and Differential Hierarchy Paper Example

Dr. Cox on DNA

As Dr. Cox mentioned, tumor suppressor genes are categorized into caretakers and gatekeepers. The caretakers incorporate the DNA repair which is a primary element in the diagnosis and treatment of cancer since they inhibit mutation accumulation. Tumor suppressor genes are essential in the completion of a cell replication cycle. They are responsible for oncogenesis regulation to inhibit the development of cancer cells. The book "The molecular basis of cancer: DNA repair pathways and human cancer" by Andrea shows that the lack of DNA repair function in cancer cells triggers the development of tumors due to genomic instability. The deficiency of DNA repair results in breaking of tumor cells and the reformation of chromosomes which lead to the disruption of tumor suppressor genes.

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Williams and Schumacher noted that 'p53 is a genome guard an important tumor suppressor gene whose function is crucial in the protection from cancer development'. p53 role in Mismatch DNA repair entails the restoration of genomic stability. The role of p53 begins in its early metazoan evolution stage where it controls the apoptotic demise of attacked cells upon the realization of a mismatch. As a result, stabilization of the DNA strand is achieved. 'p53 further allows for the removal of error strands and re-synthesis by stopping the cell cycle to give time for the DNA repair mechanism to restore genome stability.'

As highlighted by Cairns, Harris and Mark, 'functionality loss of p53 would occur as a result of homozygous recessive mutations and inactivation of normal p53 protein due to a dominant mutation that is negative in nature.' As a result, the impact of the tumor suppressor gene on the caretakers is recessive regarding risk resulting in a recessive cancer syndrome such as the Lynch syndrome. The type of medication prescribed is dependent on the patient. Chemo-preventive drugs such as aspirin and surgery would be recommended as a preventive mechanism for cancer development.

Dr. Pelech on Colon Cancer

'TP53, KRAS, PIK3CA, and BRAF are the four most commonly mutated genes in patients affected with colon cancer.' The oncogenes are in the order of decreasing frequency as per the rate of mutation. 'TP53 has the highest mutation at the rate of 43.89 % with 5750 mutations found.' Three oncogenes TP53, PIK3CA, and BRAF, belong to protein serine/threonine kinase. 'In particular, the drug recommended for BRAF include vemurafenib and dabrafenib.' On the other hand, TP53 and PIK3CA would benefit from the use of palbociclib and sorafenib. Lastly, according to Porru et al. KRAS belongs to the tyrosine protein substrate. However, there are no drugs discovered to down-regulate or inactivate the mutation of KRAS a primary oncogene in colon cancer. However, Dr. Pelech purports that more than 50% of newly formed medication will be released within the decade. Therefore, oncogenes such as KRAS will receive valuable treatment soon.

The common types of mutation in p53 and BRAF include the missense, somatic and germline. The identification of the three types of mutation ushered in a new era of colon cancer treatment based on these discoveries. An assessment of KRAS mutation is a predictive biomarker since it plays a crucial role in determining treatment for colon cancer. As a result, Neumann et al. identified glycine to aspartate on cordon 12, glycine to valine on cordon 12 and glycine to aspartate on cordon 13 as the most frequent KRAS mutation. Conversely, the mutations in PIK3CA to be analyzed include missense, somatic, and mutations that result in the alterations of the amino acid glutamic which are replaced by amino acid glycine. 'An assessment of these mutations will help in the identification of the cancer stages crucial in determining the type of treatment to be administered.'

Dr. Ong on Prostate Cancer

The hypothalamic-pituitary axis is responsible for the control of androgen testosterone production. 'Testosterone is produced by testicular Leydig cells after the luteinizing hormone stimulates it.' The hypothalamus secretes a gonadotropin-releasing hormone which stimulates the pituitary gland to release luteinizing hormone. The released androgen testosterone suppresses further secretion of luteinizing hormone resulting in a negative feedback loop. The homeostatic loop is crucial for maintaining the testosterone concentrations in the male.

An understanding of the androgen receptor (AR) signaling pathway is crucial to the development of therapies required in the handling of progressive prostate cancer patients. According to Dr. Ong, the androgen deprivation therapy is so far the ultimate model of care for patients with advanced prostate cancer. The AR signaling pathway is dependent on factors such as fluctuation in the metabolism of androgen, AR expression, and specifications of the ligand among others. During prostate cancer progression several changes in AR signaling pathway occur. The prostrate tissues incorporate dihydrotestosterone (DHT) that is converted from testosterone. The two hormones bind with DHT having the highest affinity in AR; as a result, activating AR-targeted genes. Lonegan and Tindall are of the view that AR is located at the cytoplasm when the ligand is not present resulting in an interaction with protein Filamin-A which facilitates the translocation of AR to the nucleus.

Shitivelman, Beer, and Evans purported that the inter-chromosomal rearrangements occur in 40 to 60% of prostate cancer incidences and facilitate the ERG fusions initiated by androgen-responsive promoters (TMPRSS2). The fusion results in overexpression of EZH2 and SOX9 which are crucial molecular targets during prostate cancer treatment. 'EZH2 plays a significant role in the development and progression of prostate cancer.' Drugs introduced for treatment target the enzymatic activities which are responsible for fusion development. Androgen is responsible for the fusions through cytidine deaminase and endonuclease enzymatic activities. The double-stranded DNA stop breaking upon inhibition of the enzymatic activities resulting in the control of EZH2 and SOX9. 'The regulation of overexpression of proteins such as EZH2 results in the reduction of tumorigenicity.'

The cases of cancer transmission incidence from organ donors after a transplant are low. According to Chapman, Webster, and Wong, there are few incidences when cancers exhibiting high levels of metastasis for the transplanted organs result in cancer transmission. 'Tumor cells that have a low neoantigen presentation undergo somatic mutation at a low level resulting in their ability to avoid elimination during immunoediting.' Figure 1 above is a representation of the different somatic levels exhibited by the tumor cells which are a significant determiner of the neoantigen burden. The car crash victim was diagnosed with lung cancer and had undergone radiation therapy, but cancerous cells were transmitted to the transplant recipient.

Dr. Reid on Renal Failure

The diagnosis of a malignant lesion in the kidney transplant recipient is an indication that the tumor cells had not been eliminated during the radiotherapy treatment. There is a possibility that the tumor cells had a low neoantigen representation. As a result, escaping detection in the early stages of tumorigenesis. On that note, Zhang, Yuan, Li, and Ye, suggest that it is crucial for detailed scrutiny of pathology reports for donors who had cancer initially to be undertaken even though they had received treatment due to the high risk of recurrence the cancer cells exhibit.

Minimal research has been conducted in the field of immune suppressive withdrawal. According to Londono, Rimola, O'Grady, and Sanchez-Fueyo, immune suppression withdrawal would only benefit operational tolerant recipients after organ transplantation. 'The withdrawal will aid in the reduction of side effects which will further attack the immune system in addition to the attack posed by the new organ.' Immune suppressive medication in normal occurrences is given to transplant recipients with the aim of ensuring their immune systems do not reject the new organ. 'Therefore, its withdrawal will mean the risk of the transplant recipients to fight the newly introduced organ rises. As a result, increasing the risk of death, a major downside of immune suppressive withdrawal.'

Dr. Mui on Th1 and Th2 Response

The Difference Between Th1 and Th2 Response

The main difference between Th1 and the Th2 responses is that the Th 1 responses are involved in fighting bacteria and virus inside the cells. In this case, this response deals with the infection's susceptibility as its activation leads to the regulation of the immune system. On the other hand, Th2 responses are involved in fighting against bacteria outside the host's cells, toxins, and parasites such as helminths.

The mechanism for Th1 and Th2 Responses

The Th1 mechanism involves the secretion of interferon-gamma that activates macrophages bactericidal activities. Interferon-gamma is also associated with the induction of B cells, an action which leads to the production of complement-fixing and opsonizing antibodies and results to cell-mediated immunity B. The Th2 responses are used to counteract the proinflammatory reactions produced by the Th1 cytokines and involve interleukins 5, an inducing eosinophil which aids in the elimination of parasites. Interleukin 4 is also produced and helps the isotope switching in the B cell. Besides, interleukins 5, 4 and 13 promote eosinophilic and IgE responses. interleukin-10 is produced in the Th2 mechanism and is associated with a reaction for anti-inflammatory effects.

Example of a Disease Associated with a Failure of Th2 Response

One of the conditions associated with the failure in the Th2 response is tuberculosis which is caused by bacterial infections. It should be noted that Controlling TB necessitates immunity that is cell-mediated and triggered by chemokines and cytokines. These cytokines involve Th1 effector cytokines associated with activating CD8+ T cells and macrophages to trigger bacterial and target cell killing. However, Th2 induction can lead to the impairment of CD8+ and Th1 responses aiding in the progression of TB. In normal conditions, Th2 cytokines induce macrophage activation involving a minimal bactericidal state. However, Th2 responses have been associated with promoting an antibody -initiated immunity which cannot provide resistance to the infections caused by M. tuberculosis.

In a study carried out to determine the immune responses leading in the severity and progression of tuberculosis in HIV-positive and negative patients, it was found out that immune signatures for Th2 in conjunction with SOCS3 were more prominent when severe TB cases were examined6. Besides, the immune signatures for Th2 were the main reason for the high antibody responses present in the patients exhibiting pulmonary TB. To avert this condition, future therapeutic and diagnostic approaches applied in clinical tuberculosis should consider targeting and quantifying Th2 immune responses. For instance, clinical interventions should use regulated response pathways for Th2 to avoid SOCS proteins from the excess expression, a factor which leads to immune polarization of Th2 resulting in high persistence levels in M. tuberculosis.

Dr. Rossi on Differential Hierarchy

One of the compartments of a standard differentiation hierarchy is the luminal progenitor compartment found in mammalian cells. Macias and Hinck note that the mammalian gland changes during puberty aided by the cell differentiation schemes. Studies done show that at the pre-pubertal stage, the mammary glands are made up of a rudimentary ductal structure in th...