Browsing by Author "Bosma, Nicholas"
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- ItemOpen AccessImmediate-term cognitive impairment following intravenous (IV) chemotherapy: a prospective pre-post design study(2019-02-14) Khan, Omar F; Cusano, Ellen; Raissouni, Soundouss; Pabia, Mica; Haeseker, Johanna; Bosma, Nicholas; Ko, Jenny J; Li, Haocheng; Kumar, Aalok; Vickers, Michael M; Tang, Patricia AAbstract Background Cognitive impairment is commonly reported in patients receiving chemotherapy, but the acuity of onset is not known. This study utilized the psychomotor vigilance test (PVT) and trail-making test B (TMT-B) to assess cognitive impairment immediately post-chemotherapy. Methods Patients aged 18–80 years receiving first-line intravenous chemotherapy for any stage of breast or colorectal cancer were eligible. Patient symptoms, peripheral neuropathy and Stanford Sleepiness Scale were assessed. A five-minute PVT and TMT-B were completed on a tablet computer pre-chemotherapy and immediately post-chemotherapy. Using a mixed linear regression model, changes in reciprocal transformed PVT reaction time (mean 1/RT) were assessed. A priori, an increase in median PVT reaction times by > 20 ms (approximating PVT changes with blood alcohol concentrations of 0.04–0.05 g%) was considered clinically relevant. Results One hundred forty-two cancer patients (73 breast, 69 colorectal, median age 55.5 years) were tested. Post-chemotherapy, mean 1/RT values were significantly slowed compared to pre-chemotherapy baseline (p = 0.01). This corresponded to a median PVT reaction time slowed by an average of 12.4 ms. Changes in PVT reaction times were not correlated with age, sex, cancer type, treatment setting, or use of supportive medications. Median post-chemotherapy PVT reaction time slowed by an average of 22.5 ms in breast cancer patients and by 1.6 ms in colorectal cancer patients. Post-chemotherapy median PVT times slowed by > 20 ms in 57 patients (40.1%). Exploratory analyses found no statistically significant association between the primary outcome and self-reported anxiety, fatigue or depression. TMT-B completion speed improved significantly post-chemotherapy (p = 0.03), likely due to test-retest phenomenon. Conclusions PVT reaction time slowed significantly immediately post-chemotherapy compared to a pre-chemotherapy baseline, and levels of impairment similar to effects of alcohol consumption in other studies was seen in 40% of patients. Further studies assessing functional impact of cognitive impairment on patients immediately after chemotherapy are warranted.
- ItemOpen AccessTargeting the PI3K and Ras Signal Transduction Pathways in a Murine Model of Osteolytic Breast Cancer Metastasis(2013-01-25) Bosma, Nicholas; Jirik, FrankBone metastasis frequently occurs in patients with advanced breast cancer, and leads to widespread bone destruction. Aberrant activation of the PI3K and Ras-MAPK pathways are consistently observed in high-grade metastatic breast cancers, making these pathways attractive targets for therapeutic intervention. Complex signal crosstalk between these pathways is implicated in cancer cell perpetuation; therefore, dual inhibition should theoretically provide maximal targeting. The PI3K and MEK inhibitors, PX866 and AZD6244 were employed to investigate the therapeutic potential in an in vivo model of MDA-MB-231-EGFP/Luc2 human breast cancer osteolytic metastases. PI3K inhibition did not directly affect bone-colonized cancer cells, however, it demonstrated an attenuation of bone loss, whereas MEK inhibition resulted in a significant reduction of both tumor growth and osteolysis. Simultaneous inhibition of PI3K and MEK resulted in a reduction of tumor growth, but paradoxically exhibited an exacerbation of bone damage. These findings suggest that MEK inhibition alone may be a valuable additional treatment for breast cancer osteolytic metastasis.