Publications by authors named "Joann Aaron"

10 Publications

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Pediatric patients with refractory central nervous system tumors: experiences of a clinical trial combining bevacizumab and temsirolimus.

Anticancer Res 2014 Apr;34(4):1939-45

Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1500 Holcombe Boulevard, Unit 455, Houston, TX 77030, U.S.A.

Background: Pre-clinical findings suggest that combination treatment with bevacizumab and temsirolimus could be effective against malignant pediatric central nervous system (CNS) tumors.

Patients And Methods: Six pediatric patients were treated as part of a phase I trial with intravenous temsirolimus 25 mg on days 1, 8, 15, and bevacizumab at 5, 10, or 15 mg/kg on day 1 of each 21-day cycle until disease progression or patient withdrawal.

Results: The median patient age was six years (range=3-14 years). The primary diagnoses were glioblastoma multiforme (n=2), medullobalstoma (n=2), pontine glioma (n=1) and ependymoma (n=1). All patients had disease refractory to standard-of-care (2-3 prior systemic therapies). Grade 3 toxicities possibly related to drugs used occurred in two patients: anorexia, nausea, and weight loss in one, and thrombocytopenia and alanine aminotransferase elevation in another. One patient with glioblastoma multiforme achieved a partial response (51% regression) and two patients (with medulloblastoma and pontine glioma) had stable disease for four months or more (20 and 47 weeks, respectively). One other patient (with glioblastoma multiforme) showed 18% tumor regression (duration=12 weeks).

Conclusion: The combination of bevacizumab with temsirolimus was well-tolerated and resulted in stable disease of at least four months/partial response in three out of six pediatric patients with chemorefractory CNS tumors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685166PMC
April 2014

Targeting the molecular chaperone heat shock protein 90 (HSP90): lessons learned and future directions.

Cancer Treat Rev 2013 Jun 28;39(4):375-87. Epub 2012 Nov 28.

Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Due to the critical role of heat shock protein 90 (HSP90) in regulating the stability, activity and intracellular sorting of its client proteins involved in multiple oncogenic processes, HSP90 inhibitors are promising therapeutic agents for cancer treatment. In cancer cells, HSP90 client proteins play a major role in oncogenic signal transduction (i.e., mutant epidermal growth factor receptor), angiogenesis (i.e., vascular endothelial growth factor), anti-apoptosis (i.e., AKT), and metastasis (i.e., matrix metalloproteinase 2 and CD91), processes central to maintaining the cancer phenotype. Thus, HSP90 has emerged as a viable target for antitumor drug development, and several HSP90 inhibitors have transitioned to clinical trials. HSP90 inhibitors include geldanamycin and its derivatives (i.e., tanespimycin, alvespimycin, IPI-504), synthetic and small molecule inhibitors (i.e., AUY922, AT13387, STA9090, MPC3100), other inhibitors of HSP90 and its isoforms (i.e., shepherdin and 5'-N-ethylcarboxamideadenosine). With more than 200 "client" proteins, many of them meta-stable and oncogenic, HSP90 inhibition can affect an array of tumors. Here we review the molecular structure of HSP90, structural features of HSP90 inhibition, pharmacodynamic effects and tumor responses in clinical trials of HSP90 inhibitors. We also discuss lessons learned from completed clinical trials of HSP90 inhibitors, and future directions for these promising therapeutic agents.
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http://dx.doi.org/10.1016/j.ctrv.2012.10.001DOI Listing
June 2013

Phase I Dose Escalation Study of Sodium Stibogluconate (SSG), a Protein Tyrosine Phosphatase Inhibitor, Combined with Interferon Alpha for Patients with Solid Tumors.

J Cancer 2011 Feb 10;2:81-9. Epub 2011 Feb 10.

1. Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston Texas, USA.

Purpose: Sodium stibogluconate (SSG), a small molecule inhibitor of protein tyrosine phosphatases, combined with IFN-alpha-2b (IFN-α) inhibited solid tumor cell line growth in vitro. We conducted a phase I clinical trial with SSG plus IFN-α in advanced cancer patients to assess tolerance, maximum tolerated dose (MTD) and immune system effects.

Experimental Design: SSG was administered intravenously alone for five days of week 1, cycle 1 (21 days per cycle) and together with IFN-α 2b s (3 million units sc TIW) in week 2, and after a rest during week 3, on a 2-week on/1-week off cycle. SSG dose levels were 400, 600, 900, 1125, and 1350 mg/m(2).

Results: Twenty-four patients were studied. Common toxicities included asymptomatic elevated serum lipase, thrombocytopenia, fatigue, fever, chills and anemia. The dose-limiting toxicities (DLT) were hypokalemia, thrombocytopenia, fatigue, pancreatitis and skin rash. The MTD was 900 mg/m(2 )SSG and IFN-α, 3 million units TIW. At this dose, patients had a significantly lower number of regulatory T cells (T(R )Cells) (p = 0.012), myeloid dendritic cells (mDC) (p = 0.028); higher percentage of natural killer (NK) cells that synthesized perforin (p = 0.046) and of plasmacytoid dendritic cells (pDC) that secreted IFN-α (p = 0.018) in response to activation through toll-like receptor (TLR) 7 and TLR 8 by CL097, the highly water-soluble derivative of the imidazoquinoline compound R848.

Conclusions: SSG in combination with IFN-α 2b was well tolerated and augmented cellular immune parameters.
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http://dx.doi.org/10.7150/jca.2.81DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039225PMC
February 2011

Juice plus or toxicity plus.

Am J Med 2010 Jan;123(1):e1-2

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http://dx.doi.org/10.1016/j.amjmed.2009.06.025DOI Listing
January 2010

Breast cancer: unique communication challenges and strategies to address them.

Breast J 2009 Jan-Feb;15(1):69-75. Epub 2008 Dec 12.

Department of Behavioral Science, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77230, USA.

Women with breast cancer have become increasingly more involved on a national and local level in advocating for resources to fight cancer. However, in the context of the relationship with their physicians and other cancer caregivers, much remains to be done in providing them with adequate support. In this paper, we highlight the difficulties in communication related to breast cancer and describe strategies and approaches that may be helpful in improving the communication throughout the cancer trajectory. Specifically, breast cancer patients have high unmet information needs relevant to health information and dissatisfaction with the actual information they receive from their providers. These needs seem even more pronounced when patients are older, of lower socio-economic class and from differing cultural backgrounds which may affect their ability to express their desires for information and desire to be involved in decision-making about their treatment. Other communication challenges can be envisioned as occurring at key points across the cancer trajectory: diagnosis disclosure, treatment failure, transition to palliative care, and end of life discussions. These involve techniques as basic as how to establish trust and rapport and determine a patient's information and decision-making preferences and as complex as giving bad news. These strategies are now viewed as essential skills in that they can affect patient distress and quality of life, satisfaction, and malpractice litigation as well as practitioner stress and burnout.
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http://dx.doi.org/10.1111/j.1524-4741.2008.00673.xDOI Listing
April 2009

Assessment and prognostic significance of mitotic index using the mitosis marker phospho-histone H3 in low and intermediate-grade infiltrating astrocytomas.

Am J Surg Pathol 2006 May;30(5):657-64

Department of Neuro-Oncology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Distinguishing between grade II and grade III diffuse astrocytomas is important both for prognosis and for treatment decision-making. However, current methods for distinguishing between grades based on proliferative potential are suboptimal, making identification of clear cutoffs difficult. In this study, we compared the results from immunohistochemical staining for phospho-histone H3 (pHH3), a specific marker of cells undergoing mitosis, with standard mitotic counts (number of mitoses/10 high-power fields) and MIB-1 labeling index values for assessing proliferative activity. We tested the relationship between pHH3 staining and tumor grade and prognosis in a retrospective series of grade II and III infiltrating astrocytomas from a single institution. The pHH3 index (per 1000 cells), MIB-1 index (per 1000 cells), and number of mitoses per 10 high-power fields were determined for each of 103 cases of grade II and III diffuse astrocytomas from patients with clinical follow-up. pHH3 staining was found to be a simple and reliable method for identifying mitotic figures, allowing a true mitotic index to be determined. The pHH3 mitotic index was significantly associated both with the standard mitotic count and with the MIB-1 index. Univariate analyses revealed that all 3 measurements of proliferation were significantly associated with survival. However, the pHH3 mitotic index accounted for a larger proportion of variability in survival than standard mitotic count or MIB-1/Ki-67 labeling index. After adjusting for age, extent of resection, and performance score, the pHH3 mitotic index remained an independent predictor of survival. Thus, pHH3 staining provides a simple and reliable method for quantifying proliferative potential and for the stratification of patients with diffuse astrocytomas into typical grade II and III groups. These results also suggest that pHH3 staining may be a useful method in other neoplasms in which accurate determination of proliferation potential is relevant to tumor grading or clinical treatment decision-making.
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http://dx.doi.org/10.1097/01.pas.0000202048.28203.25DOI Listing
May 2006

The prognostic impact of histology and 1p/19q status in anaplastic oligodendroglial tumors.

Cancer 2005 Oct;104(7):1468-77

Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Background: It has been reported previously that the combined loss of chromosomal arms 1p and 19q is a significant predictor of outcome for patients with anaplastic oligodendroglial (AO) tumors and that such chromosomal loss correlates with classic histology in AO. The authors sought to determine whether histology was an equivalent or superior predictor of outcome compared with 1p/19q status in 131 patients with AO tumors.

Methods: The status of 1p and 19q was determined using real-time, quantitative polymerase chain reaction analysis and/or fluorescence in situ hybridization. Clinical features (response to adjuvant therapy and tumor location) and molecular genetic abnormalities (9p and 10q deletions, overexpression of p53 and epidermal growth factor receptor) were determined on available specimens. Histologic assessments for classic oligodendroglial features were performed by five neuropathologists.

Results: Classic histology was associated closely with 1p/19q loss, as reported previously. Patients who had tumors that were considered classic by at least four of the five neuropathologists showed significantly increased progression-free and overall survival compared with the patients who had less classic tumors. The authors also tested the correlation between 1p/19q status and outcome in subsets of patients stratified according to classic tumor features. The association of 1p/19q status with survival was related closely to the presence of classic histology. Loss of 1p/19q was predictive of improved outcome only among patients who had tumors with classic histologic features.

Conclusions: The current results suggested that, in addition to 1p/19q status, histologic features contribute information to the prediction of outcome in patients with AO. Loss of 1p and 19q appeared to be a prognostic marker only in the subset of patients who had AO tumors with classic histologic features.
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http://dx.doi.org/10.1002/cncr.21338DOI Listing
October 2005

Patient-physician communication in oncology: past, present, and future.

Curr Opin Oncol 2005 Jul;17(4):331-5

Department of Neuro-Oncology, M D Anderson Cancer Center, Houston, TX 77230, USA.

Purpose Of Review: Contemporary oncology practice acknowledges the importance of partnering with the patient and family in dealing with the illness. Patients also value their physicians as important sources of support when they provide information about the illness, encouragement, and hope, discuss treatment options, and address their concerns. For this reason outcomes associated with the quality of the physician-patient relationship have received increasing recognition. This review highlights relevant studies bearing on important outcomes of communication with the cancer patient and discusses the implication for training oncologists of the future.

Recent Findings: Evidence is mounting that effective and empathic communication with the cancer patient and family can influence desirable outcomes in cancer care, which affect patient quality of life, satisfaction with care, and medical outcomes. Evidence also exists that communication and interpersonal skills can be taught and learned. Oncology training programs traditionally do not offer experience in this aspect of care although communication skills have now been defined as a core competency for oncology trainees. Finding motivated faculty to teach and providing time and structure in the curriculum are also major obstacles to be overcome.

Summary: Communication skills are the cornerstone of comprehensive cancer care. Learning this aspect of patient care can expand the supportive role of the oncologist especially at crucial times for the patient and family such as diagnosis, disease recurrence, and transition to palliative care.
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http://dx.doi.org/10.1097/01.cco.0000167738.49325.2cDOI Listing
July 2005

Silence is not golden: communicating with children dying from cancer.

J Clin Oncol 2005 May;23(15):3629-31

The University of Texas M.D. Anderson Cancer Center, Houston, TX 77230-1402, USA.

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http://dx.doi.org/10.1200/JCO.2005.11.015DOI Listing
May 2005

A noncoding RNA regulates human protease-activated receptor-1 gene during embryogenesis.

Biochim Biophys Acta 2002 Jul;1576(3):237-45

Carolina Cardiovascular Biology Center, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7126, USA.

Activation of the human protease-activated receptor-1 (PAR-1) by thrombin leads to myriad functions essential for maintaining vascular integrity. Upregulation of PAR-1 expression is considered important in atherosclerosis, angiogenesis and tumor metastasis. In vitro analysis of the human PAR-1 promoter function revealed a positive regulatory element between -4.2 and -3.2 kb of the transcription start site. This element was examined in transgenic mice containing either 4.1 or 2.9 kb of the 5' flanking sequence driving a LacZ reporter gene. Only the 4.1 kb PAR-1 transgene was expressed in vivo and only during embryonic development. The transgene expression was observed only in developing arteries and not in veins. Further examination of this putative regulatory sequence identified a novel noncoding RNA (ncR-uPAR:noncoding RNA upstream of the PAR-1) gene at -3.4 kb. The ncR-uPAR upregulated PAR-1-core promoter-driven luciferase activity and mRNA expression in vitro in a Pol II-dependent manner. This noncoding RNA appears to act in trans, albeit locally at the adjacent PAR-1 promoter. These data suggest that an untranslated RNA plays a role in PAR-1 gene expression during embryonic growth.
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http://dx.doi.org/10.1016/s0167-4781(02)00308-1DOI Listing
July 2002
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