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Pollak K.I.,Duke Comprehensive Cancer Center | Pollak K.I.,Duke University | Childers J.W.,University of Pittsburgh | Arnold R.M.,University of Pittsburgh
Journal of Palliative Medicine

Palliative care relies heavily on communication. Although some guidelines do address difficult communication, less is known about how to handle conversations with patients who express ambivalence or resistance to such care. Clinicians also struggle with how to support patient autonomy when they disagree with patient choices. Motivational Interviewing (MI) techniques may help address these responses. Specifically, MI techniques such as reflective statements and summarizing can help reduce a patient's resistance, resolve patient ambivalence, and support patient autonomy. Not all the MI techniques are applicable, however, in part because palliative care clinicians do not guide patients to make particular choices but, instead, help patients make choices that are consistent with patient values. Some elements from MI can be used to improve the quality and efficacy of palliative care conversations. © Copyright 2011, Mary Ann Liebert, Inc. 2011. Source

Teoh D.G.K.,Duke Comprehensive Cancer Center | Secord A.A.,Duke Comprehensive Cancer Center | Secord A.A.,Duke University
Cancer Control

Background: Angiogenesis is a critical component of tumor development and proliferation, and increased angiogenesis has been associated with a worse clinical outcome in a number of solid tumors, including ovarian cancer. Therefore, agents that target the angiogenic process are of considerable interest in the treatment of ovarian cancer. Methods: Studies evaluating the efficacy of antiangiogenic agents in ovarian cancer are reported. Antiangiogenic agents examined include vascular endothelial growth factor (VEGF) pathway inhibitors, including monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and a soluble receptor decoy, as well as inhibitors of other angiogenic factors and vascular disrupting agents. Results: The VEGF inhibitor bevacizumab has been shown to have efficacy in ovarian cancer in phase II trials and a progression-free survival advantage in one phase III trial. TKIs block the VEGF receptors and secondary angiogenic pathways and have shown activity in phase I and II trials. Alternative angiogenesis inhibitors include EphA2 inhibitors and a selective angiopoietin 1/2-neutralizing peptibody. Another strategy is to destroy the existing tumor vasculature, and a number of vascular disrupting agents are being studied in preclinical and phase I trials. Antiangiogenic agents have a unique side effect profile, likely due to inhibition of normal physiologic angiogenesis. Conclusions: Phase II and early phase III trials have demonstrated that antiangiogenic therapies have significant activity in ovarian cancer. The results of phase III trials in the front-line and recurrent settings will determine the extent of clinical benefit of antiangiogenic therapies in combination with chemotherapy. Antiangiogenic agents have a distinct side effect profile, and further studies are necessary to evaluate how to minimize the incidence of these events and to identify women most likely to benefit from these therapies. Source

Zhu H.,Duke University | Lo H.-W.,Duke University | Lo H.-W.,Duke Comprehensive Cancer Center
Current Genomics

Sonic hedgehog (Shh) signaling is critically important for embryogenesis and other cellular processes in which GLI transcription factors mediate the terminal effects of the pathway. GLI1, in particular, plays a significant role in human cancers. Consequently, GLI1 and its upstream positive regulator Smoothened (SMO) are important targets of anti-cancer therapy and several SMO-targeted small molecule inhibitors are being evaluated clinically. Emerging exciting evidence reveals a high level of complexity that lies within the GLI1-mediated pathway. For example, a recent study provided evidence linking the polymorphic GLI1 variants Q1100/E1100 to chronic inflammatory bowel diseases. Two recent reports uncovered the existence of two novel human GLI1 isoforms that differ structurally and functionally from the wild-type GLI1 identified over two decades ago. Interestingly, although both are products of alternative splicing, GLI1ΔN and tGLI1 (truncated GLI1) isoforms are predominantly expressed in normal and malignant tissues, respectively. In addition to these important discoveries, gene expression profiling studies have identified a number of novel wild-type GLI1 and tGLI1 target genes, linking wild-type GLI1 to tumor progression and therapeutic resistance, and tGLI1 to tumor invasion and migration. In light of these new insights, this review will provide a comprehensive overview on GLI1 polymorphisms and the three members of the GLI1 family of proteins, and their impacts on human diseases, including, cancers. © 2010 Bentham Science Publishers Ltd. Source

Shelby R.A.,Duke University | Abernethy A.P.,Duke University | Abernethy A.P.,Duke Comprehensive Cancer Center
Supportive Care in Cancer

Purpose: Sexual concerns are understudied and undertreated for patients with lung cancer. Objectives were to: (1) assess sexual concerns in lung cancer patients and examine differences by age and gender; (2) examine stability of sexual concerns over time; and (3) evaluate whether sexual concerns in lung cancer patients are significantly related to physical and emotional symptoms. Materials and methods: Data were collected from lung cancer patients during four outpatient clinic visits over 6 months. Measures included sexual concerns (reduced sexual enjoyment, interest, or performance), fatigue (FACIT Fatigue Scale), shortness of breath, and emotional distress (acute distress, despair; Patient Care Monitor). Linear mixed model analyses were conducted. Results: Sexual concerns were common, with 52% of patients reporting at least mild sexual concerns and were stable. Sexual concerns were significantly associated with physical and emotional symptoms; particularly strong relationships were found between sexual concerns and shortness of breath and emotional distress. Age moderated the relationship between both fatigue and shortness of breath and sexual concerns; gender moderated the relationship between emotional distress and sexual concerns. Conclusions: Self-reported sexual concerns are common in people with lung cancer, are stable, and are related significantly to physical and emotional symptoms; age and gender influence the distress associated with sexual symptoms in this population. Better attention to patient concerns, treatment, and more research are clearly needed. © 2010 Springer-Verlag. Source

Araujo J.C.,University of Houston | Mathew P.,Tufts Medical Center | Armstrong A.J.,Duke Comprehensive Cancer Center | Braud E.L.,Springfield Clinic | And 7 more authors.

BACKGROUND: To determine the potential efficacy of targeting both the tumor and bone microenvironment in patients with castration-resistant prostate cancer (PC), the authors conducted a phase 1-2 trial combining docetaxel with dasatinib, an oral SRC inhibitor. METHODS: In phase 1, 16 men received dasatinib 50 to 120 mg once daily and docetaxel 60 to 75 mg/m 2 every 21 days. In phase 2, 30 additional men received dasatinib 100 mg once daily/docetaxel 75 mg/m 2 every 21 days. Efficacy endpoints included changes in prostate-specific antigen (PSA), measurable disease, bone scans, and markers of bone metabolism. Safety and pharmacokinetics were also studied. RESULTS: Combination dasatinib and docetaxel therapy was generally well tolerated. Thirteen of 46 patients (28%) had a grade 3-4 toxicity. Drug-drug interactions and a maximum tolerated dose were not identified. Durable 50% PSA declines occurred in 26 of 46 patients (57%). Of 30 patients with measurable disease, 18 (60%) had a partial response. Fourteen patients (30%) had disappearance of a lesion on bone scan. In bone marker assessments, 33 of 38 (87%) and 26 of 34 (76%) had decreases in urinary N-telopeptide or bone-specific alkaline phosphatase levels, respectively. Twenty-eight patients (61%) received single-agent dasatinib after docetaxel discontinuation and had stabilization of disease for an additional 1 to 12 months. CONCLUSIONS: The high objective response rate and favorable toxicity profile are promising and justify randomized studies of docetaxel and dasatinib in castration-resistant PC. Parallel declines in levels of PSA and bone markers are consistent with cotargeting of epithelial and bone compartments of the cancer. Treatment with single-agent dasatinib following docetaxel cessation warrants further study. Copyright © 2011 American Cancer Society. Source

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