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Comprehensive Assessment of the Elderly Cancer Patient: The Feasibility of Self-Report Methodology

PURPOSE Comprehensive geriatric assessment (CGA) has aided the medical community greatly in understanding the quality-of-life issues and functional needs of older patients. With its professional team assessment approach, however, CGA may be time consuming and costly. The goal of the present study was to assess the ability of cancer patients to complete a self-administered CGA and then to characterize cancer patients across multiple domains and age groups. PATIENTS AND METHODS Two hundred sixty-six male outpatient oncology patients at the Durham Veterans Affairs Medical Center were asked to fill out a survey assessing 10 domains (demographics, comorbid conditions, activities of daily living, functional status, pain, financial well being, social support, emotional state, spiritual well-being, and quality of life). RESULTS Seventy-six percent of the patients who received their surveys and kept their appointments returned the assessment tool. Older oncology patients had significantly less education (P <.0001), income (P =.05), frequent exercise (P =.01), and chance of being disease free (P =.003) than younger patients. Other findings in older patients were a higher rate of marriage (P =.02), more difficulty in taking medications (P =.05), and less cigarette (P =.03) and alcohol (P =.03) use. Members of all age cohorts reported a sense of social support, with younger patients deriving this more from family and friends than older patients, and older patients deriving social support more from membership in religious communities than younger patients. No differences were found across age groups for number and impact of comorbid illnesses, number of medications, basic and instrumental activities of daily living, pain, overall health rating, financial adequacy, anxiety, depression, and quality of life. CONCLUSION CGA can be conducted in an outpatient cancer community using a self-report format. Despite the fact that this population varied demographically across age groups and is limited to veterans, this study demonstrated remarkable similarities between younger and older cancer patients in terms of functional status, health states, and quality of life.

The Role of SATB1 in Breast Cancer Pathogenesis

BACKGROUND SATB1 has been previously proposed as a key protein that controls the development and progression of breast cancer. We explored the potential of the SATB1 protein as a therapeutic target and prognostic marker for human breast cancer. METHODS We used aggressive (MDA-MB-231 and BT549) and nonaggressive (SKBR3 and MCF7) breast cancer cell lines to investigate the potential of SATB1 as a therapeutic target. SATB1 mRNA expression was silenced in aggressive cells by use of short hairpin RNAs against SATB1. SATB1 was overexpressed in nonaggressive cells by use of SATB1 expression vectors. We assessed the effect of modifying SATB1 expression on the transformed phenotype by examining anchorage-independent cell proliferation, acinar morphology on matrigel, and migration by wound healing in cultured cells. We examined tumor formation and metastasis, respectively, by use of orthotopic mammary fat pad and tail vein xenograft mouse models (mice were used in groups of six, and in total, 96 mice were used). SATB1 mRNA expression was compared with outcome for patients with primary breast cancer from six previous microarray studies that included a total of 1170 patients. All statistical tests were two-sided. RESULTS The transformed phenotype was not suppressed by SATB1 silencing in aggressive cells and was not enhanced by ectopic expression of SATB1 in nonaggressive cells. Modifying SATB1 expression did not alter anchorage-independent cell proliferation, invasive acinar morphology, or cell migration in cultured cells and did not affect tumor formation or metastasis in xenograft mouse models. In addition, SATB1 expression was not associated with decreased overall survival of patients with primary breast cancer in six previous independent microarray studies (overall odds ratio = 0.80, 95% confidence interval = 0.62 to 1.03, P = .10). CONCLUSION In contrast to previous studies, we found that SATB1 expression did not promote breast cancer progression and was not associated with breast cancer outcome.

Statistical expression deconvolution from mixed tissue samples

Motivation: Global expression patterns within cells are used for purposes ranging from the identification of disease biomarkers to basic understanding of cellular processes. Unfortunately, tissue samples used in cancer studies are usually composed of multiple cell types and the non-cancerous portions can significantly affect expression profiles. This severely limits the conclusions that can be made about the specificity of gene expression in the cell-type of interest. However, statistical analysis can be used to identify differentially expressed genes that are related to the biological question being studied. Results: We propose a statistical approach to expression deconvolution from mixed tissue samples in which the proportion of each component cell type is unknown. Our method estimates the proportion of each component in a mixed tissue sample; this estimate can be used to provide estimates of gene expression from each component. We demonstrate our technique on xenograft samples from breast cancer research and publicly available experimental datasets found in the National Center for Biotechnology Information Gene Expression Omnibus repository. Availability: R code (http://www.r-project.org/) for estimating sample proportions is freely available to non-commercial users and available at http://www.med.miami.edu/medicine/x2691.xml Contact: jclarke@med.miami.edu

Retinoic Acid Receptor-β2 Promoter Methylation in Random Periareolar Fine Needle Aspiration

Methylation of the retinoic acid receptor-β2 (RARβ2) P2 promoter is hypothesized to be an important mechanism for loss of RARβ2 function during early mammary carcinogenesis. The frequency of RARβ2 P2 methylation was tested in (a) 16 early stage breast cancers and (b) 67 random periareolar fine needle aspiration (RPFNA) samples obtained from 38 asymptomatic women who were at increased risk for breast cancer. Risk was defined as either (a) 5-year Gail risk calculation ≥1.7%; (b) prior biopsy exhibiting atypical hyperplasia, lobular carcinoma in situ, or ductal carcinoma in situ; or (c) known BRCA1/2 mutation carrier. RARβ2 P2 promoter methylation was assessed at two regions, M3 (−51 to 162 bp) and M4 (104-251 bp). In early stage cancers, M4 methylation was observed in 11 of 16 (69%) cases; in RPFNA samples, methylation was present at M3 and M4 in 28 of 56 (50%) and 19 of 56 (38%) cases, respectively. RPFNAs were stratified for cytologic atypia using the Masood cytology index. The distribution of RARβ2 P2 promoter methylation was reported as a function of increased cytologic abnormality. Methylation at both M3 and M4 was observed in (a) 0 of 10 (0%) of RPFNAs with Masood scores of ≤10 (nonproliferative), (b) 3 of 20 (15%) with Masood scores of 11 to 12 (low-grade proliferative), (c) 3 of 10 (30%) with Masood scores of 13 (high-grade proliferative), and (d) 7 of 14 (50%) with Masood scores of 14 of 15 (atypia). Results from this study indicate that the RARβ2 P2 promoter is frequently methylated (69%) in primary breast cancers and shows a positive association with increasing cytologic abnormality in RPFNA.

The association between oral health and general health and quality of life in older male cancer patients

Objectives: To describe the long‐term effects of oral health problems on quality of life (QoL), functional status, pain, and general health in older male cancer patients.

Effects of cancer history and comorbid conditions on mortality and healthcare use among older cancer survivors

Older cancer survivors use healthcare services to an increased extent relative to their counterparts who have no history of malignant disease. In the current study, the authors set out to assess the effects of cancer history and comorbid conditions on healthcare use and mortality.

Geriatric oncology: past, present, future.

Efforts to integrate geriatric oncology principles in the training of all medical oncologists are underway.

Will Periodic Intravenous Injections of Conditioned Bone Marrow Cells Effectively Reduce Atherosclerosis

Maintenance of healthy arteries requires a balance between injuries to the arterial wall and processes of intrinsic arterial repair. Such repair requires the availability of progenitor cells that are local to the wall itself. Progenitor cells from distant reservoirs like the bone marrow may also contribute to repair. Arterial repair seems to degrade over a lifetime, particularly with risk factors such as smoking and diabetes. Hence, a potential preventive/therapeutic strategy for atherosclerosis could be transfusion of competent bone marrow cells (BMCs) to restore effective repair in the face of arterial injury and depleted endogenous repair reservoirs. The challenge with this strategy has been the reliable collection and/or generation of BMCs that support arterial repair. In this study, we describe a set of experiments to elucidate a method of culturing BMCs that robustly retards atherosclerosis development in apolipoprotein E knockout mice. Identifying such a method would represent an important step in developing cell-based treatments for patients with proclivity for developing atherosclerosis.

Characteristics of cross-hybridization and cross-alignment of expression in pseudo-xenograft samples by RNA-Seq and microarrays

BackgroundExploring stromal changes associated with tumor growth and development is a growing area of oncologic research. In order to study molecular changes in the stroma it is recommended to separate tumor tissue from stromal tissue. This is relevant to xenograft models where tumors can be small and difficult to separate from host tissue. We introduce a novel definition of cross-alignment/cross-hybridization to compare qualitatively the ability of high-throughput mRNA sequencing, RNA-Seq, and microarrays to detect tumor and stromal expression from mixed ‘pseudo-xenograft’ samples vis-à-vis genes and pathways in cross-alignment (RNA-Seq) and cross-hybridization (microarrays). Samples consisted of normal mouse lung and human breast cancer cells; these were combined in fixed proportions to create a titration series of 25% steps. Our definition identifies genes in a given species (human or mouse) with undetectable expression in same-species RNA but detectable expression in cross-species RNA. We demonstrate the comparative value of this method and discuss its potential contribution in cancer research.ResultsOur method can identify genes from either species that demonstrate cross-hybridization and/or cross-alignment properties. Surprisingly, the set of genes identified using a simpler and more common approach (using a ‘pure’ cross-species sample and calling all detected genes as ‘crossers’) is not a superset of the genes identified using our technique. The observed levels of cross-hybridization are relatively low: 5.3% of human genes detected in mouse, and 3.5% of mouse genes detected in human. Observed levels of cross-alignment are practically comparable to the levels of cross-hybridization: 6.5% of human genes detected in mouse, and 2.3% of mouse genes detected in human. We also observed a relatively high percentage of orthologs: 40.3% of cross-hybridizing genes, and 32.2% of cross-aligning genes.Normalizing the gene catalog to use Consensus Coding Sequence (CCDS) IDs (Genome Res 19:1316–1323, 2009), our results show that the observed levels of cross-hybridization are low: 2.7% of human CCDS IDs are detected in mouse, and 2.4% of mouse CCDS IDs are detected in human. Levels of cross-alignment using the RNA-Seq data are comparable for the mouse, 2.2% of mouse CCDS IDs detected in human, and 9.9% of human CCDS IDs detected in mouse. However, the lists of cross-aligning/cross-hybridizing genes contain many that are of specific interest to oncologic researchers.ConclusionsThe conservative definition that we propose identifies genes in mouse whose expression can be attributed to human RNA, and vice versa, as well as revealing genes with cross-alignment/cross-hybridization properties which could not be identified using a simpler but more established approach. The overall percentage of genes affected by cross-hybridization/cross-alignment is small, but includes genes that are of interest to oncologic researchers. Which platform to use with mixed xenograft samples, microarrays or RNA-Seq, appears to be primarily a question of cost and whether the detection and measurement of expression of specific genes of interest are likely to be affected by cross-hybridization or cross-alignment.

NOTCH1 IS ASSOCIATED WITH THE DEVELOPMENT OF TRI-LEAFLET CALCIFIC AORTIC STENOSIS

The prevalence of tri-leaflet calcific aortic stenosis continues to grow. An understanding of the genetic role of the disease is important in the development of preventative therapies. We performed a two-center genome wide association study (GWAS) of aortic stenosis. A control group was compared to