Histone Deacetylase Inhibitors and Breast Cancer Metastasis: A Review and Exploration of HDAC(i)s and Other Chemotherapeutic Agents

The traditional perspective of Histone Deacetylase enzymes is focused on their inherent epigenetic modification characteristics. While it is true that the histone modification these enzymes exhibit play a role in cancer and related diseases, Histone Deacetylase has a variety of non-histone targets. The non-histone targets include microtubules and are of specific interest because of the microtubules’ role in cell line differentiation, replication, apoptosis, and cancer metastasis. Using a variety of Histone Deacetylase Inhibitors (HDACi) and other chemotherapeutic compounds, our research group explored the HDACi effect on breast cancer cell lines. Our goal was to indicate the presence of HDACi cell-line dependent cancer growth inhibition and to study the hypothesized non-histone mechanism of microtubule modification in HDACi(s). The experiment consisted of three parts: viability assay, clonogenic assay, and combination assay which analyzed HDACi(s) possible synergistic character with microtubule-stabilizing compounds. The specific breast cancer cell lines used were MDA-MB-231 clones LM-4175 and BOM-1833, and MCF7-BOM. The results of our experiments indicated that there was cell line dependent growth inhibition with the treatment of HDACi(s). Specifically, MCF7-BOM showed to be more susceptible to treatment, and this could be due to it being an estrogen receptor positive ER+ cell line. However, the growth inhibition never reached complete inhibition and was most prominent at the highest concentrations of HDACi(s). Higher concentrations of HDACi(s) also had the most prominent effect on colony growth inhibition in the clonogenic assay. The combination assay had an interesting result indicating an antagonistic trend between microtubule stabilizers and HDACi(s)

Oregon vegetable digest ; Vol. 11 No. 1

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The Effect of Race and Sex on Physicians' Recommendations for Cardiac Catheterization

Background Epidemiologic studies have reported differences in the use of cardiovascular procedures according to the race and sex of the patient. Whether the differences stem from differences in the recommendations of physicians remains uncertain. Methods We developed a computerized survey instrument to assess physicians' recommendations for managing chest pain. Actors portrayed patients with particular characteristics in scripted interviews about their symptoms. A total of 720 physicians at two national meetings of organizations of primary care physicians participated in the survey. Each physician viewed a recorded interview and was given other data about a hypothetical patient. He or she then made recommendations about that patient's care. We used multivariate logistic-regression analysis to assess the effects of the race and sex of the patients on treatment recommendations, while controlling for the physicians' assessment of the probability of coronary artery disease as well as for the age of the patient, the level of coronary risk, the type of chest pain, and the results of an exercise stress test. Results The physicians' mean (±SD) estimates of the probability of coronary artery disease were lower for women (probability, 64.1±19.3 percent, vs. 69.2±18.2 percent for men; P<0.001), younger patients (63.8±19.5 percent for patients who were 55 years old, vs. 69.5±17.9 percent for patients who were 70 years old; P<0.001), and patients with nonanginal pain (58.3±19.0 percent, vs. 64.4±18.3 percent for patients with possible angina and 77.1±14.0 percent for those with definite angina; P<0.001). Logistic-regression analysis indicated that women (odds ratio, 0.60; 95 percent confidence interval, 0.4 to 0.9; P=0.02) and blacks (odds ratio, 0.60; 95 percent confidence interval, 0.4 to 0.9; P=0.02) were less likely to be referred for cardiac catheterization than men and whites, respectively. Analysis of race–sex interactions showed that black women were significantly less likely to be referred for catheterization than white men (odds ratio, 0.4; 95 percent confidence interval, 0.2 to 0.7; P=0.004). Conclusions Our findings suggest that the race and sex of a patient independently influence how physicians manage chest pain