Controlled studies conducted within the nursing profession have consistently demonstrated that, while traditional and allopathic medicinal practices such as "digital rectal examination, prostate-specific antigen, and transrectal ultrasound have been identified as effective means of early detection of prostate cancer, African-American men tend to underuse these services as compared to white men" (Agho and Lewis, 2001), and these findings have serious implications for the medical community. In order to fully accomplish the goal of preventing and treating disease, nurses and doctors must strive to bridge the gap which exists between the medical profession and the African-American community (Boehm et al
Jones, Taylor and their fellow researchers also found that the higher rate of prostate cancer within African-American populations was linked to a widespread cultural distrust of health care providers and the use of complementary and alternative modalities (CAMs) of health care that this mistrust entails. The authors find that when nurses and doctors "acknowledge that spiritual and religious beliefs are prevalent among African-American men," this acknowledgment "may help healthcare professionals provide a more supportive environment" (Jones et al
, 2007), and their report concludes that an appreciation of cultural beliefs on the part of healthcare providers may encourage African-American men to pursue traditional treatment options in addition to less effective alternatives. In a nation which has known deep racial division throughout its history, the fact that "for decades, African-American men have had the highest prostate cancer incidence rate of any raciallethnic group in the world" (McIntosh, 1997) is quite alarming and suggests that the consequences of institutionalized prejudice are felt long after outright bigotry is abolished
). USP14 is the mammalian ortholog of the yeast deubiquitinase (DUB) Ubp6 and Ubp6/USP14 has been shown to reversibly associate with the19S RP proteosomal subunit (D'Arcy, Wang, & Linder, 2015)
The mechanistic link between autophagy and repair of DSBs may depend in part on DUB activity, since Beclin-1, an adapter protein critical to the assembly of phagophores, increases the stability of USP10 and USP13. Relevantly, human breast, ovarian, and prostate tumor cells have lost one beclin-1 allele and belcin-1 heterozygous-null mice more readily develop lymphomas, carcinomas, and other cancers (Glick, Barth, & Macleod, 2010)
Treating breast and ovarian cancer cells with a small molecule inhibitor for USP14 and Chloriquine induced caspase-independent programmed cells death in a synergistic manner. The effect of these treatments on DSB repair by non-homologous end-joining (NHEJ) can be determined by measuring the levels of ?-H2AX and polyubiquitylated ?-H2AX (Ikura et al
The fourth and final aim of this proposal will involve experiments designed to evaluate whether USP14 inhibition can restore DSB repair in synthetic lethal for homologous recombination (HR) and NHEJ. Synthetic lethality due to defective HR and NHEJ activities can be induced a number of ways, including treatment with small molecule inhibitors of APE1, ATM kinase, DNA-PKs, and DSB repair (Kinner, Wu, Staudt, & Iliakis, 2008)
USP14-null mice are grossly normal except for synaptic abnormalities, which suggest normal ubiquitin recycling in synapses depends on USP14 activity. Recent research findings suggest autophagy may play an important role in the repair of DNA double-strand breaks (DSBs), based on evidence showing inhibition of autophagy sensitizes cells to ionizing radiation (Liu et al
The expectation would be that inhibition of USP14 activity would increase proteosome activity, interact synergistically with Chloriquine to induce cell death (Vogel et al., 2015), and possibly result in the accumulation of ?-H2AX (Nijnik et al
, 2015). Research findings have also revealed ubiquitylation plays a critical regulatory role in autophagy, as does the trimming of ubiquitin moieties by DUBs (Vogel et al
A third option is to leave the prostate as is and consider adapting to the urinary challenges and embracing tactics and techniques to eliminate unpleasant or annoying side effects, such as frequent urination. These practices could include clamps and milking as well as the administration of anticholinergic and an alpha-blocker, which would assist in the urination pains and frequency problems (Chou, 2011)
Each of these possibilities should be checked and ruled off the list, but prior to doing so, some steps must be taken to educate the patient about the causes of his terminal dysuria. The fact that he is being treated for hypertension and hypercholesterolemia suggests that this terminal dysuria may be the result of kidney stones, which have been linked to both hypertension and hypercholesterolemia (Hamano, Nakatsu, Suzuki, Tomioka, Tanaka, Murakami, 2005)
Therefore, education is important for the patient at this point. First of all, the patient should be made aware that LUTS is common in older men (Parsons, 2010) and that one in three men will develop some form of voiding problem, which can improve over time: it is not necessarily a worsening symptom