tbuckley/cabot-search huggingface dataset:
Accurate response assessment of breast cancer bone metastasis using computed tomography and new response criteria
Authors: T. Hamaoka, J. E. Madewell, C. M. Costelloe, R. Islam, G. Rondon, G. D. Ayers, R. E. Champlin, D. A. Berry, G. N. Hortobagyi, N. T. Ueno
Journal: Journal of Clinical Oncology (2005)

568 Background: The lack of accurate criteria for assessing the response of bone metastases from breast cancer has led to bone disease being considered unmeasurable. Criteria from the UICC and the WHO based on radiography (XR) and skeletal scintigraphy (SS) are not satisfactory for clinical use. Criteria for computed tomography (CT) and magnetic resonance imaging (MR) have yet to be validated. We recently proposed a set of CT- and MR-inclusive criteria (MDA) to assess bone response (JCO 22:2942, 2004). Here we retrospectively reviewed image sets to evaluate the accuracy of MDA criteria (vs UICC, WHO) and the accuracy of each imaging modality for assessing bone response. Methods: XR, SS, CT, and MR images from patients with breast cancer and bone-only metastases were reviewed by musculoskeletal radiologists at baseline and after treatment (early: 2–6 mo, late: 11–13 mo). Responses were characterized as complete or partial, or stable or progressive disease (CR, PR, SD or PD) according to the 3 sets of criteria (MDA, WHO, UICC). Results from each imaging modality were compared with clinical evidence of response (symptoms, tumor markers, imaging). Results: We reviewed 180 image sets from 47 patients and analyzed images from 41 patients. At the early phase, we found that CT was more sensitive (77%; 95% CI 54–99; P=0.03) than SS (36%; 95% CI 11–61), and MDA criteria were more sensitive (87%; 95% CI 69–100; P=0.02) than WHO (40%; 95% CI 15–65) for detecting response. Specificity was no different among modalities or criteria. Those with CR or PR by MDA criteria early in treatment may have had better overall survival than nonresponders (SD+PD) (HR 0.4; 95% CI 0.17–1.14; P=0.09), with no difference by WHO criteria (HR 1.0; 95% CI 0.38–2.56; P=0.98). We could not examine XR, MR, or UICC criteria because too few XR and MR images were available. Conclusions: CT is more sensitive than SS for showing clinical response of bone lesions from breast cancer. The MDA criteria is more likely to be appropriate than WHO criteria for assessing bone metastases from breast cancer. Prospective studies are warranted to determine whether use of the CT- and MR-inclusive MDA criteria improves the ability to detect and quantify responses in bone metastases. No significant financial relationships to disclose.
Bevacizumab and improvement of progression-free survival (PFS) for patients with the mesenchymal molecular subtype of ovarian cancer.
Authors: Boris J. N. Winterhoff, Stefan Kommoss, Ann L. Oberg, Chen Wang, Shaun M. Riska, Gottfried E. Konecny, Jian-Bing Fan, Viji Shridhar, Ellen L. Goode, Friedrich Kommoss, Andreas Du Bois, Felix Hilpert, Jeremy Chien, Andrew Christopher Embleton, Mahesh Parmar, Richard S. Kaplan, Timothy Perren, Lynn C. Hartmann, Jacobus Pfisterer, Sean Christopher Dowdy
Journal: Journal of Clinical Oncology (2014)

5509 Background: ICON7 demonstrated that the addition of bevacizumab to carboplatin and paclitaxel improves progression free survival (PFS), but not overall survival (OS) in first-line treatment of ovarian cancer. Our aim was to determine if response to bevacizumab was associated with the molecular classification as described by The Cancer Genome Atlas (TCGA) project. Methods: Core biopsies from formalin fixed paraffin embedded (FFPE) tissue blocks were examined to ensure >70% tumor nuclei from 425 of 455 ICON7 patients enrolled in Germany. Quality Illumina Whole-Genome DASL HT global gene expression data was generated to stratify 380 (89%) patients into four TCGA subclassifications. Median PFS with 95% confidence intervals (CI) and log rank tests were used to evaluate treatment effect on PFS in the presence of non-proportional hazards. Results: Molecular classification was as follows: 86 were differentiated (23%), 124 immunoreactive (33%), 73 mesenchymal (19%), and 97 proliferative (25%). The groups were balanced over treatment arms. 267 (70.3%) were of serous histology. Patients with serous carcinomas of mesenchymal subtype obtained the greatest benefit from bevacizumab with an improvement of median PFS of 9.5 months (25.5 [95%CI 21.1, NA] vs. 16 [95%CI 10.5, NA] months, p=0.053). In contrast, the differentiated, immunoreactive and proliferative subtypes demonstrated median PFS improvements of 5.8 (19.4 [18.6, NA] vs. 13.6 [9.7, 32.7], p=0.35), 3.4 (17.9 [15.9, NA] vs. 14.6 [12.4, NA], p=0.38) and 3.2 months (21.5 [19.8, 29] vs. 18.3 [13.8, NA], p=0.76), respectively. Patients with mesenchymal tumors or high risk clinical characteristics (suboptimal stage III, all stage IV) (46% of cohort) demonstrated a 7.3 month improvement in median PFS with bevacizumab (19.8 [18.3, 23.7] vs. 12.5 [10.1, 16.2] months, p<0.01). Conclusions: Assignment to molecular subclassifications based on gene expression signatures was feasible using FFPE tissue. Patients with mesenchymal subtype ovarian cancer may be most likely to obtain sustained benefit from treatment with bevacizumab.
Abstract 146: Biphasic Effect Of Cyclic Amp Axis On Cardiomyocyte Survival
Authors: Morihiko Aoyama, Yasuko K Bando, Haruya Kawase, Akio Monji, Toyoaki Murohara
Journal: Circulation Research (2014)

Background: Persistent cardiac hypertrophy in response to pathological stimuli is results in maladaptive myocardial remodeling and cell death. Clinical evidence revealed that one of the most significantly beneficial medications for targeting heart failure with pathologic myocardial hypertrophy is beta1-adrenergic receptor (β1R) blockers. The molecular pathway of β1R is mediated by the second messenger cyclic AMP (cAMP). However, there are some debate regarding the role of cAMP in myocardial survival. We hypothesized whether there may be threshold concentration of cAMP in cell susceptibility to cardiomyocyte cell death. Methods: Male 14-week-old C57BL6 mice were subjected to the surgery of thoracic aortic constriction (TAC) to induce pressure overload. Changes in apoptosis were evaluated in each heart section and in vitro culture of neonatal cardiomyocytes using TUNEL. To elucidate the concentration-dependent distinct effect of cAMP on myocardial cell death, we tested the different concentration of cell-permeable cAMP (8-br-cAMP) at low (60 μM) and high concentration (6 mM), and receptor-mediated cAMP-stimulators (Ex4; exendin-4, ISO; isoproterenol). Results: In vitro analysis revealed that the high-cAMP and ISO exhibited marked increase in TUNEL-positivity (15.46%±3.09% for high-cAMP versus 6.71%±0.33% for ISO), which was reversed by Rp-cAMP (1.80%±0.17% and 2.05%±0.25%, respectively). Unexpectedly, the 8-p-Methoxyphenylthon-2-O-methyl-cAMP (pMe-cAMP, 50 μM), the specific activator of another cAMP-sensitive target Epac, reversed the high-cAMP-induced cell death even at a less extent compared to that observed by PKA-inhibitor Rp-cAMP (3.73%±0.70%). Serum depletion induced 3.22±0.24% of TUNEL-positive cell count of NRVM, which was reversed by pMe-cAMP, (50 μM) and Ex4 (1.74±0.18%, n=6, P&lt;0.01), which was insensitive to PKA inhibition by Rp-cAMP (100 μM). TAC increased myocardial apoptosis. TAC-CON heart exhibited 1.66-fold decrease in cardiac cAMP concentration compared to sham-CON. Ex4 ameliorated the TAC-induced cardiac dysfunction and apoptosis by increase in cAMP. Conclusions: The cAMP-related cell death was mediated by PKA activation, which were reversed by Epac activation.
Socioeconomic and Clinical Factors Are Key To Uncovering Disparity in Accrual Onto Therapeutic Trials for Breast Cancer
Authors: Carolyn E. Behrendt, Arti Hurria, Lusine Tumyan, Joyce C. Niland, Joanne E. Mortimer
Journal: Journal of the National Comprehensive Cancer Network (2014)

To monitor and address disparity in accrual, patient participation in cancer clinical trials is routinely summarized by race/ethnicity. To investigate whether confounding obscures racial/ethnic disparity in participation, all women with breast cancer treated by medical oncologists at City of Hope Comprehensive Cancer Center from 2004 through 2009 were classified by birthplace and self-reported race/ethnicity, and followed for accrual onto therapeutic trials through 2010. Undetectable on univariate analysis, significantly reduced participation by subjects of African, Asian, Eastern European, Latin American, and Middle Eastern ancestries was revealed after accounting for age, socioeconomic factors, tumor and oncologist characteristics, and intrapractice clustering of patients.
Chromosomal Changes of Immunoglobulin-Producing Cell Lines from Human Lymph Nodes With and Without Lymphoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Eero Saksela, Jan Pontén, III
Journal: JNCI Journal of the National Cancer Institute (1968)

Chromosomal studies of immunoglobulin-producing “lympho-blastoid”cell lines derived from two malignant lymphomas and two histologically normal lymph nodes revealed a varying proportion of chromosomally abnormal cells intermingled with normal diploid cells. Chromosomally, the abnormal cell populations were clonal. Repeatedly the same marker karyotypes were found in most of the abnormal cells within each culture, but the changes were dissimilar between cultures. Characteristically, the chromosomal abnormalities were single trisomies resulting in 47 chromosome cells and marker chromosomes whose origin was obvious in most instances. Numerical variation was generally within normal limits, and in some, cells with normal diploid karyotype formed the majority. As the cultures were followed, a chromosomally altered population was replaced by another in two cultures, but the type of the produced immunoglobulin was unchanged.
Expression of Murine Gamma Fetal Antigen in Adult Hematopoietic Tissue and During Induced Differentiation of Friend Erythroleukemia Cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: P J Higgins, A E Silverstone, C Bueti, V F Pizzi, M R Melamed, M Lipkin, F Traganos
Journal: JNCI Journal of the National Cancer Institute (1986)

Quantitative analysis of extracts of various normal adult CD-1 mouse tissues indicated that the serologically defined murine gamma fetal antigen (gamma-FA) was expressed at high levels in hematopoietic tissue in general and in bone marrow (BM) in particular. Metabolic labeling of isolated BM cells indicated that the BM was a site of gamma-FA synthesis in the adult animal. The size(s) of the antigen immunoprecipitated from labeled BM cells (35 and 27 kilodaltons) with anti-gamma-FA serum correlated well with molecular weight estimates of fibrosarcoma-fetal mouse-associated gamma-FA, as determined by molecular sieve chromatography. For ascertainment of the relationship between hematopoietic cell differentiation and gamma-FA content, a multiparameter flow cytometric approach was used to evaluate gamma-FA levels in Friend erythroleukemia (FL) cells as a function of growth state (blast or dimethyl sulfoxide-differentiated) and cell-cycle compartment. Differentiated G1-arrested FL cells (G1D) possessed significantly lower gamma-FA-associated immunofluorescence as compared to control cells in the G0-G1 substate. Remaining S- and G2 + M-phase cells in differentiated populations demonstrated an even greater reduction in gamma-FA content relative to control cells in the corresponding cell-cycle phases. The available data support the tentative classification of gamma-FA as a murine differentiation antigen.
Insulin resistance, estimated by serum C-peptide level, is associated with reduced event-free survival for postmenopausal women in NCIC CTG MA.14 adjuvant breast cancer trial
Authors: M. N. Pollak, J. W. Chapman, L. Shepherd, D. Meng, P. Richardson, C. Wilson, B. Orme, K. I. Pritchard
Journal: Journal of Clinical Oncology (2006)

524 Background: NCIC CTG MA.14 is a randomized multi-centre trial of tamoxifen versus combined tamoxifen and octreotide LAR therapy in the adjuvant treatment of breast cancer in post-menopausal women. Planned secondary analyses included investigation of baseline metabolic factors that might influence survival. Laboratory and clinical studies indicate that insulin resistance is associated with adverse outcome in breast cancer. Insulin resistance elevates C-peptide levels. Methods: In MA.14, trial patients with stage I or II postmenopausal breast cancer were randomized from September, 1996 until July, 2000 to receive 20 mg tamoxifen PO daily for 5 years with/without the administration of the somatostatin analogue Octreotide LAR 90 mg depot injection monthly for 2 years. Event-free survival (EFS), the trial’s primary outcome measure, was defined as time from randomization to time of recurrence of primary disease, time of second malignancy or death due to any cause. We investigated the effect of baseline IGF-I, IGFBP-3, and C-peptide levels on EFS. Kaplan-Meier univariate and Cox step-wise multivariate regressions were performed with/without adjustment for the stratification factors of adjuvant chemotherapy, nodal status, and hormone receptor status, and included patient age (years) and tumour size (T-status). Results: These results are based on analysis of patient serum for the trial’s 667 patients. Median follow-up for those alive is 6.1 years; patients experienced 165 events. Higher C-peptide levels were associated with significantly worse EFS in adjusted, and unadjusted, univariate and multivariate analyses. Final efficacy analyses are expected within a few months. Updated analyses for the effects of baseline metabolic markers and body mass index on EFS will be presented. Conclusions: This is the largest data set, and the first clinical trial, linking higher serum C-peptide levels to adverse outcome in patients with early breast cancer. These results raise concern in the context of increasing population prevalence of insulin resistance. Potential novel adjuvant therapies exist as insulin resistance is modifiable. [Table: see text]
Abstract 1960: Ginger consumption may delay the onset of prostate cancer
Authors: Tonya S. Lane, Ricardo M. Richardson
Journal: Cancer Research (2015)

Abstract Ginger active components are widely known for being a potent antioxidant and recently as a potential anticancer agent. To date, the precise mechanism(s) for the antitumor effect of ginger is not well understood. An active chemical component of ginger, 6-gingerol, was recently shown to inhibit angiogenesis and tumorigenesis. In this study we investigated the role of ginger in prostate cancer growth and proliferation using PCa cell lines from African American (AA) and Caucasian American (CA) men. To that end, MDA-PCa 2b (AA), LnCap (CA) and PC-3 (CA) cells were treated with different concentrations of 6-gingerol or 6-shogaol for 24 hours and cell proliferations were measured by XTT assay. To determine the effect of 6-gingerol in cell signaling, cell lysates were assayed for β-arrestin 1 and 2 expression, MAP kinase and caspase activity by Western Blotting. The data demonstrated that 6-gingerol inhibits cellular proliferation and promotes apoptosis in both AA and CA PCa cell lines. These effects correlated with decrease in β -arrestin 2, not β -arrestin 1, expression and Akt phosphorylation but increased caspase activity. Taken together the data suggests that 6-gingerol inhibits PCa growth and promotes PCa apoptosis via a βarr-2/Akt-dependent mechanism. Since PC-3 cells do not express AR, the data likely indicates that 6-gingerol effect is independent of AR activation and PSA expression. Citation Format: Tonya S. Lane, Ricardo M. Richardson. Ginger consumption may delay the onset of prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1960. doi:10.1158/1538-7445.AM2015-1960
The Diagnostic Interview for Depressive Personality
Authors: J G Gunderson, K A Phillips, J Triebwasser, R M Hirschfeld
Journal: American Journal of Psychiatry (1994)

The development of a new structured interview for depressive personality disorder is described.A literature search yielded 32 traits associated with depressive personality; these traits were then used to develop the interview. Interrater reliability for the interview was tested in an initial group of 16 patients with longstanding depressive personality traits. Data from a second group of 67 subjects--54 with a possible clinical diagnosis of depressive personality and 13 normal volunteers--were used to examine the interview's psychometric properties and to modify its content. Factor analysis of the traits in the interview and modification of the instrument's structure was carried out on the basis of data from a third group of 526 subjects who were participating in a large epidemiologic study of mood disorders.The Diagnostic Interview for Depressive Personality, which emerged from this process, assess 30 personality traits that were shown to have satisfactory interrater reliability (kappa = 0.67), test-retest reliability (kappa = 0.41), and diagnostic reliability (kappa = 0.62). A cutoff score of 42 (from a total possible score of 60) on the interview offers a useful threshold for diagnosis.This interview provides a reliable method for assessing depressive personality traits and establishing the diagnosis of depressive personality disorder.
Concurrent Chemotherapy and Radiation: A Major Advance for Women With Cervical Cancer
Authors: Patricia J. Eifel
Journal: Journal of Clinical Oncology (1999)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.5.1334 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10334515 Concurrent Chemotherapy and Radiation: A Major Advance for Women With Cervical Cancer Patricia J. EifelxPatricia J. EifelSearch for articles by this author Show More The University of Texas/M.D. Anderson Cancer Center, Houston, TX https://doi.org/10.1200/JCO.1999.17.5.1334 Full Text PDF Figures and Tables "Concurrent Chemotherapy and Radiation: A Major Advance for Women With Cervical Cancer." Journal of Clinical Oncology, 17(5), p. 1334© 1999 by American Society of Clinical Oncology
Abstract P372: Association of Pre-pregnancy Body Mass Index with Stroke and Coronary Heart Disease Mortality
Authors: Morgana L Mongraw-Chaffin, Wendy L Bennett
Journal: Circulation (2012)

Background: Few studies have investigated the relationship between body mass index (BMI) measured before middle age and cardiovascular disease mortality in women. We hypothesized that higher pre-pregnancy BMI would be associated with increased stroke and coronary heart disease (CHD) mortality. Methods: We conducted a retrospective cohort study using the Child Health and Development Studies cohort of 10,889 women enrolled between 1959 and 1967 at the time of pregnancy diagnosis. Stroke and CHD death were assessed annually by matching study participants to the California Department of Motor Vehicles and the California Vital Status Records. We calculated pre-pregnancy BMI using self-reported pre-pregnancy weight and height measured at enrollment. Self-reported weights were similar to weights measured at the first visit. Covariates included age, race/ethnicity, education, total family income, smoking status, parity, and co-morbid conditions such as chronic hypertension, pre-pregnancy diabetes, and kidney disease. We used parametric survival analysis to calculate hazard ratios for stroke and CHD death for each BMI category. Results: At enrollment, mean age was 26.9 years, 66% (7190 of 10,889) were Caucasian, and 24% (2632 of 10,889) were African American. During a mean follow-up of 28.5 years, 1518 participants died. Among these, 79 participants died from stroke and 205 from CHD. Classified by pre-pregnancy BMI, 1008 women had a BMI &lt;18.5, 8406 had a BMI 18.5-24.9, 1143 had a BMI 25-29.9, and 332 had a BMI ≥ 30. With increasing BMI, participants had higher prevalence of pre-pregnancy co-morbid conditions, higher age and parity, and lower family income. In adjusted models, higher pre-pregnancy BMI was associated with increased stroke and CHD risk compared to normal BMI ( Table 1 ). Conclusion: We identified an association between pre-pregnancy BMI and cardiovascular mortality. Pregnancy may offer an opportunity to promote behavior change in women with elevated BMI to reduce later life risk for cardiovascular disease. Table 1. Adjusted hazard ratios for stroke and CHD mortality by pre-pregnancy BMI BMI Category Stroke Coronary Heart Disease &lt;18.5 1.33 (0.57, 3.13) 0.91 (0.48, 1.75) 18.5 - 24.9 1.0 (REF) 1.0 (REF) 25.0 - 29.9 1.75 (0.97, 3.14) 2.20 (1.53, 3.16) ≥ 30.0 3.61 (1.69, 7.69) 4.35 (2.70, 7.01)
Association Between Serum Level of Hepatitis B Surface Antigen at End of Entecavir Therapy and Risk of Relapse in E Antigen–Negative Patients
Authors: Yao-Chun Hsu, Lein-Ray Mo, Chi-Yang Chang, Ming-Shiang Wu, Jia-Horng Kao, Wen-Lun Wang, Tzeng-Huey Yang, Chaur-Shine Wang, Ming-Feng Chiang, Chieh-Chang Chen, Yu-Jen Fang, Hsu-Wei Hung, Chun-Ying Wu, Jaw-Town Lin
Journal: Clinical Gastroenterology and Hepatology (2016)
ATPS-10DEXMEDETOMIDINE ALTERS MOLECULAR PROFILE AND CELLULAR PROPERTIES OF GLIOBLASTOMA
Authors: Markus Luedi, Sanjay Singh, Eric Sulman, Frederick Lang, Rivka Colen, Pascal Zinn
Journal: Neuro-Oncology (2015)

Different cellular and molecular effects of the alpha-2-receptoragonist Dexmedetomidine have been reported and the drug is becoming of essence in glioblastoma (GBM) care for both, awake craniotomies and in postoperative intensive care. Glioblastoma stem cells (GSCs) are an established model for preclinical GBM research. However, the effects of Dexmedetomidine on GSCs expression profile is unknown. The purpose of this research was to establish the drugs impact on the expression profiles and cellular properties of GSCs. Two independent GSC lines were exposed to Dexmedetomidine. miRNA and mRNA expression profiling by microarrays was performed using total RNA. In silico analysis were performed with ingenuity pathway analyses (IPA) and gene ontology (GO) analysis. Changes in cellular properties such as self-renewal (limiting dilution assay), differentiation (neural lineage marker analysis), proliferation (BrdU labeling), and invasion (Boyden chamber assays) were investigated upon Dexmedetomidine treatment. Dexmedetomidine treatment altered the cellular and molecular profiles of GSCs. Ingenuity pathway analyses and gene ontology analysis of differentially expressed genes in Dexmedetomidine exposed cells revealed multiple cellular functions being potentially affected. Comprehensive in vitro experiments with GSCs including differentiation, proliferation, self-renewal and migration/invasion assays show that the alpha-2-receptor-agonist can potentially impact GBM pathogenesis by significantly altering cellular behavior of GSCs. With this in silico and in vitro approach we could show how Dexmedetomidine influences GSCs on cellular and molecular level. Respecting these results offers opportunities to enhance prognosis for patients being treated for GBM by adapting the usage of this alpha-2-receptor-agonist.
Prognosis in Resected Invasive Mucinous Adenocarcinomas of the Lung: Related Factors and Comparison with Resected Nonmucinous Adenocarcinomas
Authors: Ho Yun Lee, Min Jae Cha, Kyung Soo Lee, Hee Young Lee, O Jung Kwon, Joon Young Choi, Hong Kwan Kim, Yong Soo Choi, Jhingook Kim, Young Mog Shim
Journal: Journal of Thoracic Oncology (2016)