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Kimberly Blackwell

Sarah L Sammons, Donna L Topping, Kimberly L Blackwell
Cyclin-dependent kinase (CDK) 4/6 inhibitor-based therapies have shown great promise in improving clinical outcomes for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Addition of a CDK4/6 inhibitor to endocrine therapy increases efficacy and delays disease progression. Successful use of CDK4/6 inhibitor-based therapies in the clinic requires insight into the unique side-effect profiles of this class of agents and effective patient monitoring...
March 30, 2017: Current Cancer Drug Targets
Antonino Musolino, Mario Campone, Patrick Neven, Neelima Denduluri, Carlos H Barrios, Javier Cortes, Kimberly Blackwell, Hatem Soliman, Zsuzsanna Kahan, Hervé Bonnefoi, Matthew Squires, Yong Zhang, Stephanie Deudon, Michael M Shi, Fabrice André
BACKGROUND: Overexpression of fibroblast growth factor receptor 1 (FGFR1), found in ≤8% of hormone receptor-positive (HR(+)), human epidermal growth factor receptor 2-negative (HER2(-)) breast cancer cases, is correlated with decreased overall survival and resistance to endocrine therapy (ET). Dovitinib, a potent FGFR inhibitor, has demonstrated antitumor activity in heavily pretreated patients with FGFR pathway-amplified breast cancer. METHODS: In this randomized, placebo-controlled phase II trial, we evaluated whether the addition of dovitinib to fulvestrant would improve outcomes in postmenopausal patients with HR(+), HER2(-) advanced breast cancer that had progressed during or after prior ET...
February 10, 2017: Breast Cancer Research: BCR
Joseph K Vasquez, Yftah Tal-Gan, Gabriel Cornilescu, Kimberly A Tyler, Helen E Blackwell
The bacterial pathogen Staphylococcus aureus controls many aspects of virulence by using the accessory gene regulator (agr) quorum sensing (QS) system. The agr system is activated by a macrocyclic peptide signal known as an autoinducing peptide (AIP). We sought to develop structurally simplified mimetics of AIPs for use as chemical tools to study QS in S. aureus. Herein, we report new peptidomimetic AgrC receptor inhibitors based on a tail-truncated AIP-II peptide that have almost analogous inhibitory activities to the parent peptide...
December 22, 2016: Chembiochem: a European Journal of Chemical Biology
Grace R Anderson, Suzanne E Wardell, Merve Cakir, Lorin Crawford, Jim C Leeds, Daniel P Nussbaum, Pallavi S Shankar, Ryan S Soderquist, Elizabeth M Stein, Jennifer P Tingley, Peter S Winter, Elizabeth K Zieser-Misenheimer, Holly M Alley, Alexander Yllanes, Victoria Haney, Kimberly L Blackwell, Shannon J McCall, Donald P McDonnell, Kris C Wood
Therapies that efficiently induce apoptosis are likely to be required for durable clinical responses in patients with solid tumors. Using a pharmacological screening approach, we discovered that combined inhibition of B cell lymphoma-extra large (BCL-XL) and the mammalian target of rapamycin (mTOR)/4E-BP axis results in selective and synergistic induction of apoptosis in cellular and animal models of PIK3CA mutant breast cancers, including triple-negative tumors. Mechanistically, inhibition of mTOR/4E-BP suppresses myeloid cell leukemia-1 (MCL-1) protein translation only in PIK3CA mutant tumors, creating a synthetic dependence on BCL-XL This dual dependence on BCL-XL and MCL-1, but not on BCL-2, appears to be a fundamental property of diverse breast cancer cell lines, xenografts, and patient-derived tumors that is independent of the molecular subtype or PIK3CA mutational status...
December 14, 2016: Science Translational Medicine
Gabriel N Hortobagyi, Salomon M Stemmer, Howard A Burris, Yoon-Sim Yap, Gabe S Sonke, Shani Paluch-Shimon, Mario Campone, Kimberly L Blackwell, Fabrice André, Eric P Winer, Wolfgang Janni, Sunil Verma, Pierfranco Conte, Carlos L Arteaga, David A Cameron, Katarina Petrakova, Lowell L Hart, Cristian Villanueva, Arlene Chan, Erik Jakobsen, Arnd Nusch, Olga Burdaeva, Eva-Maria Grischke, Emilio Alba, Erik Wist, Norbert Marschner, Anne M Favret, Denise Yardley, Thomas Bachelot, Ling-Ming Tseng, Sibel Blau, Fengjuan Xuan, Farida Souami, Michelle Miller, Caroline Germa, Samit Hirawat, Joyce O'Shaughnessy
Background The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). Methods In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease...
November 3, 2016: New England Journal of Medicine
S Harrison Farber, Vadim Tsvankin, Jessica L Narloch, Grace J Kim, April K S Salama, Gordana Vlahovic, Kimberly L Blackwell, John P Kirkpatrick, Peter E Fecci
Brain metastases represent the most common type of brain tumor. These tumors offer a dismal prognosis and significantly impact quality of life for patients. Their capacity for central nervous system (CNS) invasion is dependent upon induced disruptions to the blood-brain barrier (BBB), alterations to the brain microenvironment, and mechanisms for escaping CNS immunosurveillance. In the emerging era of immunotherapy, understanding how metastases are influenced by the immunologic peculiarities of the CNS will be crucial to forging therapeutic advances...
July 2016: Oncoimmunology
Zahi Mitri, Rita Nanda, Kimberly Blackwell, Colleen M Costelloe, Ilona Hood, Caimiao Wei, Abenaa M Brewster, Nuhad K Ibrahim, Kimberly B Koenig, Gabriel N Hortobagyi, Catherine Van Poznak, Mothaffar F Rimawi, Stacy Moulder-Thompson
PURPOSE: Osteoclast-mediated bone resorption through src kinase releases growth factors, sustaining bone metastases. This trial determined the recommended phase II dose (RP2D) and clinical efficacy of the src kinase inhibitor dasatinib combined with zoledronic acid in bone predominant, HER2-negative breast cancer metastases. EXPERIMENTAL DESIGN: A 3+3 lead in phase I design confirmed the RP2D allowing activation of the single-arm, phase II trial. Zoledronic acid was administered intravenously on day 1, and dasatinib was given orally once daily for 28 days each cycle as twice daily administration caused dose-limiting toxicity (DLT)...
December 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Albert P Kausch, Michael Tilelli, Joel Hague, Christopher Heffelfinger, David Cunha, Maria Moreno, Stephen L Dellaporta, Kimberly Nelson
Wide crosses have been used for decades as a method for transferring novel genetic material and traits in plant breeding. Historically, many products of wide crosses require tedious and inefficient surgical embryo rescue prior to embryo abortion to recover single plantlets. We have utilized transgenic switchgrass (Panicum virgatum L. cv Alamo) as a pollen donor in conjunction with antibiotic or herbicide selection for recovery of intra-and interspecific F1 crosses by using developing ovules from the female parent and selecting for embryogenic cultures derived from the in situ immature embryo...
November 2016: Plant Biotechnology Journal
Kimberly Blackwell, Roman Donskih, C Michael Jones, Allen Nixon, Maria J Vidal, Roumen Nakov, Pritibha Singh, Gregor Schaffar, Pere Gascón, Nadia Harbeck
BACKGROUND: Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. In highly regulated markets, there are currently no approved biosimilars of pegfilgrastim. Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare proposed biosimilar LA-EP2006 with reference pegfilgrastim (Neulasta, Amgen) in early-stage breast cancer patients receiving adjuvant or neoadjuvant myelosuppressive chemotherapy...
July 2016: Oncologist
Nadia Harbeck, Oleg Lipatov, Mona Frolova, Dmitry Udovitsa, Eldar Topuzov, Doina Elena Ganea-Motan, Roumen Nakov, Pritibha Singh, Anita Rudy, Kimberly Blackwell
AIM: This randomized, double-blind trial compared proposed biosimilar LA-EP2006 with reference pegfilgrastim in women receiving chemotherapy for breast cancer (PROTECT-1). PATIENTS & METHODS: Women (≥18 years) were randomized to receive LA-EP2006 (n = 159) or reference (n = 157) pegfilgrastim (Neulasta(®), Amgen) for ≤6 cycles of (neo)-adjuvant TAC chemotherapy. Primary end point was duration of severe neutropenia (DSN) during cycle 1 (number of consecutive days with absolute neutrophil count <0...
June 2016: Future Oncology
Kathleen K Harnden, Kimberly L Blackwell
No abstract text is available yet for this article.
March 2016: Pediatrics
Rachel A Freedman, Rebecca S Gelman, Jeffrey S Wefel, Michelle E Melisko, Kenneth R Hess, Roisin M Connolly, Catherine H Van Poznak, Polly A Niravath, Shannon L Puhalla, Nuhad Ibrahim, Kimberly L Blackwell, Beverly Moy, Christina Herold, Minetta C Liu, Alarice Lowe, Nathalie Y R Agar, Nicole Ryabin, Sarah Farooq, Elizabeth Lawler, Mothaffar F Rimawi, Ian E Krop, Antonio C Wolff, Eric P Winer, Nancy U Lin
PURPOSE: Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. PATIENTS AND METHODS: Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection...
March 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Carrie A Franzen, Robert H Blackwell, Kimberly E Foreman, Paul C Kuo, Robert C Flanigan, Gopal N Gupta
PURPOSE: Exosomes are small secreted vesicles that contain proteins, mRNA and miRNA with the potential to alter signaling pathways in recipient cells. While exosome research has flourished, few publications have specifically considered the role of genitourinary cancer shed exosomes in urine, their implication in disease progression and their usefulness as noninvasive biomarkers. In this review we examined the current literature on the role of exosomes in intercellular communication and as biomarkers, and their potential as delivery vehicles for therapeutic applications in bladder, prostate and renal cancer...
May 2016: Journal of Urology
Matthew T Roe, Derek D Cyr, Debra Eckart, Phillip J Schulte, Michael A Morse, Kimberly L Blackwell, Neal E Ready, S Yousuf Zafar, Anne W Beaven, John H Strickler, Jane E Onken, Kenneth J Winters, Lisa Houterloot, Dmitry Zamoryakhin, Stephen D Wiviott, Harvey D White, Dorairaj Prabhakaran, Keith A A Fox, Paul W Armstrong, E Magnus Ohman
AIMS: Studies have suggested increased cancer incidence associated with long-term dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). We evaluated cancer incidence and treatment-related differences in an analysis of DAPT for ACS. METHODS AND RESULTS: The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial enrolled 9326 participants with ACS, who received aspirin plus clopidogrel or prasugrel...
January 21, 2016: European Heart Journal
Neil L Spector, Faith C Robertson, Sarah Bacus, Kimberly Blackwell, Deborah A Smith, Kelli Glenn, Leanne Cartee, Jennifer Harris, Carie L Kimbrough, Mark Gittelman, Eli Avisar, Peter Beitsch, Kevin M Koch
PURPOSE: The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in plasma as a surrogate for tumor concentrations. To examine this plasma-tumor relationship, we explored the association between lapatinib levels in tumor and plasma in mice and humans, and those effects on phosphorylation of human epidermal growth factor receptors (HER) in human tumors...
2015: PloS One
Gretchen Kimmick, Sara N Edmond, Hayden B Bosworth, Jeffrey Peppercorn, Paul K Marcom, Kimberly Blackwell, Francis J Keefe, Rebecca A Shelby
PURPOSE: To explore how symptoms and psychosocial factors are related to intentional and unintentional non-adherent medication taking behaviors. METHODS: Included were postmenopausal women with hormone receptor positive, stage I-IIIA breast cancer, who had completed surgery, chemotherapy, and radiation, and were taking endocrine therapy. Self-administered, standardized measures were completed during a routine clinic visit: Brief Fatigue Inventory, Brief Pain Inventory, Menopause Specific Quality of Life Questionnaire, Functional Assessment of Cancer Therapy General and Neurotoxicity scales, and Self-Efficacy for Appropriate Medication Use Scale...
October 2015: Breast: Official Journal of the European Society of Mastology
Brett R Blackwell, Kimberly J Wooten, Michael D Buser, Bradley J Johnson, George P Cobb, Philip N Smith
Studies of steroid growth promoters from beef cattle feedyards have previously focused on effluent or surface runoff as the primary route of transport from animal feeding operations. There is potential for steroid transport via fugitive airborne particulate matter (PM) from cattle feedyards; therefore, the objective of this study was to characterize the occurrence and concentration of steroid growth promoters in PM from feedyards. Air sampling was conducted at commercial feedyards (n = 5) across the Southern Great Plains from 2010 to 2012...
July 21, 2015: Environmental Science & Technology
Catherine G Coughlin, Katherine A Blackwell, Christine Bartley, Madeleine Hay, Kimberly A Yonkers, Michael H Bloch
OBJECTIVE: Antipsychotic medications are used by increasing numbers of women of reproductive age. The safety of these medications during pregnancy has not been well described. We undertook a systematic review and meta-analysis of the adverse obstetric and neonatal outcomes associated with exposure to antipsychotics during pregnancy. DATA SOURCES: PubMed, Reprotox, and were searched to identify potential studies for inclusion. METHODS OF STUDY SELECTION: Case-control or cohort studies estimating adverse birth outcomes associated with antipsychotic exposure during pregnancy were included...
May 2015: Obstetrics and Gynecology
Kathleen Harnden, Kimberly Blackwell
Zoledronic acid, a potent nitrogen-containing bisphosphonate, plays a key role in preventing complications of bone metastases in metastatic breast cancer, but its affect on early-stage breast cancer has been unclear. The preclinical data supporting the anticancer effects of zoledronic acid are compelling and several recent clinical trials have suggested that it reduces breast cancer recurrence in certain patient subgroups. Given these anticancer effects and reasonable safety profile, this therapeutic option could be discussed with patients...
April 2015: Journal of the National Comprehensive Cancer Network: JNCCN
Sharareh Siamakpour-Reihani, Kouros Owzar, Chen Jiang, Peter M Scarbrough, Oana I Craciunescu, Janet K Horton, Holly K Dressman, Kimberly L Blackwell, Mark W Dewhirst
PURPOSE: We have previously reported that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion patterns obtained from locally advanced breast cancer (LABC) patients prior to neoadjuvant therapy predicted pathologic clinical response. Genomic analyses were also independently conducted on the same patient population. This retrospective study was performed to test two hypotheses: (1) gene expression profiles are associated with DCE-MRI perfusion patterns, and (2) association between long-term overall survival data and gene expression profiles can lead to the identification of novel predictive biomarkers...
June 2015: International Journal of Hyperthermia
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