Characteristics Of Prostate Cancer

One of the two pyruvate molecules that was generated from glycolysis enters the mitochondrial matrix where it is converted to acetyl CoA. Acetyl CoA initiates a cyclical series of reactions, creating the first compound in the Krebs cycle by transforming the last product formed in the Krebs cycle into Citrate. During the Krebs cycle, 1 ATP molecule is created and 3 molecules of carbon dioxide are released. Since only 1 of the 2 pyruvates is needed, the Krebs cycle repeats and six carbon dioxide molecules are released and the Krebs cycle forms two more ATP. Krebs cycle produces several molecules of NADH and FADH2, which will be used in creating more ATP in the third step of aerobic cellular respiration.

The anti-apoptotic mutations related to cytochrome c are not the only mechanisms acquired by cells in the development of a tumor. Another important hallmark of cancer is the alteration of cellular metabolism, also known as the Warburg Effect, which demonstrates an increased rate of glycolysis despite the presence of oxygen in tumor cells (Hallmarks). Due to the unlimited and uncontrollable division by tumorigenic cells, the Warburg Effect confers growth advantages compared to non-proliferating cells because it promotes the uptake of glucose, it produces less reactive oxygen species (ROS), and it generates ATP more rapidly than oxidative phosphorylation, all of which are considered to facilitate rapid growth and survival (1).

Each year approximately 233,000 men will be diagnosed with prostate cancer (Eggener, Cifu, & Nabhan, 2015). In 2015, prostate cancer was the second most common cancer related cause of death among United States men (Eggener, et. al., 2015). While the majority of prostate cancers are slow growing with a 5-year survival rate of approximately 98%, statistics show that when prostate cancer is identified as metastatic, the 5-year survival rate dramatically drops down to 20-25% (Eggener, et. al., 2015). According to these numbers alone, it appears screening for prostate cancer would be a well-accepted practice. However, current methods of screening for this cancer are controversial and has lead organizations like the U.S Preventative Service Task Force (USPSTF) and the American Cancer Society (ACS) to different guidelines for screening.

In order to enter the mitochondria, fatty acids are oxidised to fatty acyl-coA. The breakdown of ATP to AMP and pyrophosphate provides energy for this process. Moreover, fatty acyl-coA cannot pass through the inner mitochondrial membrane. Hence, the enzyme carnitine acyl transferase I replaces the coA with carnitine and then fatty acyl-carnitine passes through the acyl-carnitine I carnitine transporter into the mitochondrial matrix. In the matrix, fatty acyl-coA is regenerated by carnitine acyltransferase II. This allows beta oxidation to occur where fatty acid chains split into several molecules of acetyl-coA, yielding one NADH and one FADH2. This process involves the removal of two carbons from the carboxyl chain leading to a fatty acyl-coA chain two carbons shorter through four reactions. In reaction 1, oxidation dehydrogenation occurs converting fatty acyl-coA to trans-Δ2-enoyl-coA. This is catalyzed by the enzyme acyl-coA-dehydrogenase and electrons are transferred to FAD , reducing it to FADH2. Reaction 2 is catalyzed by enoyl-coA-hydratase, where trans-Δ2-enoyl-coA is hydrated to L-β-hydroxyl-acyl-coA. Reaction 3 is catalysed by β-hydroxyl-coA dehydrogenase, where two electrons are transferred fo NAD+ to form NADH, and β ketoacyl-coA is formed. In reaction 4, thiolytic cleavage causes the two carbons at the

Through many cancer researches in the last decades, it was found that cancer cells often use glucose more voraciously and quite differently from normal cells. Therefore, many researchers and pharmaceutical companies have thought that the nutrient supply and deprivation of the cancer cells will potentially be the next target in disrupting the metabolism of cancer cells.

Prostate cancer originates in the secretory epithelial compartment of the prostate. The major function of these cells is to secrete protein components of prostatic fluid such as MSMB. With progression to metastasis, cells proliferate faster and lose their differentiated secretory phenotype. Expression of the mRNA of tumor suppressors and many cytoskeletal proteins decline. On the other hand, expression of genes associated with cell cycle [cyclins and cyclin dependent kinases] and protection from apoptosis [BIRC5] increase. As tumors grow, they become hypoxic due to characteristics of the tumor specific blood supply.

All living organisms require a source of energy for survival and optimum biological function, this source of energy is manifested in the form of Adenosine Triphosphate (ATP). Cellular respiration is the separation of natural compounds which discharges pent up energy, leading to the formation of ATP (Upadhyaya, 2017). This ATP is then applied to various functions around the cell by the use of the anaerobic process of glycolysis which produces 2 ATP (Upadhyaya, 2017). The generation of more ATP, as many cells need, requires an aerobic process in the mitochondria of the cell, following the production of 2 more ATP molecules from the Krebs cycle, which results in a yield of 34 ATP per every glucose molecule dissembled (Upadhyaya, 2017). The cells who are satisfied with the ATP

Lay Abstract: Prostate cancer is a complex disease with multiple tumors originating independently at different stages of growth. Although morphological differences (morphological heterogeneity) has been well recognized, the underlying molecular complexity in each tumor foci has not been well studied. Tumor growth in each foci can be determined by independent driver molecular aberration(s). Understanding the molecular level of differences (molecular heterogeneity) in each tumor foci would help to differentiate the patients who may undergo indolent or aggressive disease course. Further, morphological differences mostly help to understand the stage of the disease, but it is not possible to select appropriate targeted therapy. If different tumor foci carry different driver molecular aberrations, targeted therapy for single molecular aberrations may not yield the curative benefit to the patients. Conventionally, systematic sampling of large tumor foci or high Gleason grade tumor foci have been considered for various genetic and molecular studies. In this approach smaller tumor foci with important driver molecular aberration and high metastatic potential can be easily missed. Therefore, using our novel approach, we propose to screen the entire prostate tissue (whole-mount prostatectomy specimen mounted on large glass slide) to assess molecular differences in each tumor foci using well characterized prostate cancer specific molecular markers.

Peroxynitrite is a powerful oxidant, formed from the reaction of nitric oxide and superoxide. It is known to interact with different biological molecules like DNA, lipids and proteins leading to their structural and functional alterations. These events elicit various cellular responses including cell signaling causing oxidative damage, committing cells to apoptosis or necrosis. The present paper delineates single strand breakage in DNA mediated by the formation of 8-nitroguanine and 8-oxoguanine. Different approaches of cell death such as necrosis and apoptosis are modulated by cellular energetics (ATP and NAD+). High concentrations of peroxynitrite are known to cause necrosis whereas low concentration leads to apoptosis. Peroxynitrite mediated

This complex converts pyruvate to acetyl CoA, which is necessary for the initiation of the Krebs cycle that ultimately leads to adenosine triphosphate (ATP) production. When thiamin is depleted, the conversion of pyruvate to acetyl CoA is blocked, promoting pyruvate accumulation in the cytosol and eventual lactate production (Gunnerson & Harvey, 2016). The anaerobic pathway of converting pyruvate to lactate is inefficient, producing only 2 moles of ATP compared to the 30 moles of ATP produced during aerobic respiration. Additionally, a lack of ATP following thiamin deficiency shifts energy metabolism to fat stores, which produces ketones for the production of acetyl CoA. However, fat stores are eventually depleted in chronic thiamin deficiency (Dinicolantonio et al.,

Prostate cancer is the development of cancer in the prostate. Researches on how nutrients affect the incidence or progression of prostate cancer will continue due to the fact that no diet have been proven to have a final cure on prostate cancer. Good nutrition may help in reducing the risk of developing prostate cancer. No studies have shown that these nutrients combination recommended would be of benefits in altering the growth of an existing cancer, but it is believed that these nutrients improves the quality of life which in turn reduces the risk of early death. Nutrition also plays a role in the occurrence of prostate cancer.

Succinyl CoA inhibits α- ketoglutarate dehydrogenase and citrate synthase. The enzyme, α- ketoglutarate dehydrogenase, catalyzes the oxidative decarboxylation of α- ketoglutarate (where equilibrium is attained far to the right towards succinyl CoA) and is allosterically inhibited by succinyl CoA. Citrate synthase is also inhibited by succinyl CoA where in the TCA cycle it is converted to oxaloacetate. Therefore, elevated generation of succinyl CoA does not just produce additional oxaloacetate; it also reduces the rate at which it is converted to citrate via inhibition of citrate synthase.

Prostate cancer is the leading mortality cancer amongst males. This cancer is due to the signaling increase of androgen and androgen receptors, which is a gene that associates with the risk of prostate cancer. Over expression of androgen receptors occurs in androgen independent cancer. Prostate tumors advance to androgen-independent state where they progress in the absence of circulating testosterone. Typically, treatments for prostate cancer are surgery and radiation. Most effective treatments in the early stage of prostate cancer includes suppression of AR function either by blocking androgen signaling with anti-androgen bicalutanmide (Casodex) or flutamide or by inhibiting the conversion of testosterone to the potent androgen

If we take a look at an example about prostate cancer, with the data collected by Hastie, Tibshirani, Friedman in The Elements of Statistical Learning [2] and view the scatterplot in figure 1.1, we can see that the dependent variable, the log of the prostate specific antigen (lpsa) has a strong positive correlation particularly with lcavol (the log cancer volume) and lcp (the log of capsular penetration) with weaker but still strong correlations with the other dependent variables, log prostate weight (lweight), age, log of the amount of benign prostatic hyperplasia (lbph), and percent of Gleason scores 4 or 5 (pgg45), but not the svi (seminal vesicle invasion) and gleason (gleason score) as these are categorical variables [2]. Below figures 1.2 and 1.3 were fit with all variables and figures 1.4 and 1.5 were simplified by removing variables that had high p values until I felt that the model was better improved and they were fit thereafter. When we plot the fitted values against the residuals, if there is linearity, we should get an even spread around the line at 0. If we look at figures 1.2 and 1.4, for which the R coding can be found in the appendix below (section 7), we can see that they both seem to have linearity with figure 1.2 having possible outliers further away from the line and figure 1.4 having a more even spread. Taking a look at figure 1.3 we can see that there is a particularly good fit along the middle but the tails have fairly large variation, suggesting a

According to the Prostate Cancer Foundation, African American men are a staggering 1.6 times more likely to develop prostate cancer than Caucasian men and and overwhelming 2.4 times more likely to die from prostate cancer compared to caucasian men. As odd as it might sound, African American men living in the United States have the highest risk factor in the world for prostate cancer. African American men living in the United States are a whopping 60 times more likely to develop prostate cancer than men living in the lowest countries on the risk factor scale which is China and Japan. While there is not a direct answer to why African Americans are at a higher risk for prostate cancer, there are many epidemiological reasons that could elevate the risk factor in African American males. (1)