Over the last two decades, since the discovery of Drosophila mutants in 1995, much effort has been made to understand Aurora kinase biology. Three mammalian subtypes have been identified thus far which include the Aurora A, B and C kinases. These regulatory proteins specifically work at the cytoskeleton and chromosomal structures between the kinetochores and have vital functions in the early phases of the mitotic cell cycle. Today, there are multiple phase I and phase II clinical trials as well as numerous preclinical studies taking place looking at Aurora kinase inhibitors in both hematologic and solid malignancies. This review focuses on the preclinical and clinical development of Aurora kinase inhibitors in hematological malignancy and discusses their therapeutic potential.
Background: Breast cancer is the most common cancer in women worldwide. With early detection and advancement in treatment, majority of women diagnosed with breast cancer will be cured. Some of these breast cancer survivors report Cognitive Impairment (CI) also known as “chemo-brain” or “mental fog”, especially those who have received chemotherapy. Few studies using functional neuroimaging have been conducted to foresee possible neurological alterations that could be linked to CI but research in this area remains in its early stages. Cognivue ® is an FDA cleared medical device that helps in assessment of cognitive dysfunction using novel computerized technology and is reported to be useful in detecting early stages of CI. Methods: We conducted a pilot study at the Lipson Cancer Institute/Rochester General Hospital for evaluation of CI in patients with breast cancer who received curative chemotherapy within the last 12 months of enrollment and self-reported CI. We enrolled 23 female patients between ages 19 and 90 years. Patients were subjected to Mini Mental Status Examination (MMSE) and St. Louis University Mental Status examination (SLUMS) as well as Cognivue ® testing. MMSE and SLUMS were scored according to scoring range guidance and digital data was obtained from the Cognivue® software. Analysis was performed using correlations of numeric data, ANOVA with Tukey’s post-hoc tests for categorical data, and Positive/Negative Percent Agreement (PPA/NPA) analysis for comparison of all cognitive testing methods. Results: Cognivue ® provides higher sensitivity to evaluate CI than MMSE and SLUMS, mainly in detecting earlier stages of CI. The cognitive domains most affected were executive function, abstraction and memory. There was a statistically significant correlation between Cognivue/CI score and duration of chemotherapy (p = 0.02). Age, type of chemotherapy or hormonal status of breast cancer were not significantly related with CI. Conclusions: Cognivue appears to be beneficial in its ability to detect CI in breast cancer patients. Specifically, detection of impairment in executive function domain could be predictive of daily life activity issues in such patients post-chemotherapy. This study also provides a possibility of detecting early cognitive dysfunction as well as the potential to develop a predictive algorithm of early intervention strategies for better patient outcomes. Citation Format: Manasi M Godbole, Mukul Singal, Reina Benabou, Iqra Choudary, Mehul P Patel. Objective measurement of cognitive impairment in breast cancer survivors who received chemotherapy with the use of novel computerized testing [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-07.
The pediococci are gram-positive bacteria that grow in pairs and tetrads and belong to the lactic acid bacteria group. They are used extensively in industry to ferment cheese and other dairy products, soy products, and alcoholic beverages, and they are normal inhabitants of the human gastrointestinal tract. Of the 13 species of pediococci, only Pediococcus acetolactic and P. pentosaceus are typically found in sugar-rich foods, and these have been identified as human pathogens. Recently, pediococci have been increasingly recognized as a cause of bacteremia, endocarditis, and pneumonitis in the immunocompromised host. The chapter discusses risk factors for Pediococcus infections that include prior antibiotic therapy, abdominal surgery, and gastric feeding. The chapter further discusses the testing, evaluation, and treatment of patients presenting with possible pediococcal disease.
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