tbuckley/cabot-search huggingface dataset:
Abstract P200: The Circadian Pattern of Cardiac Autonomic Modulation and its Correlates in Adolescents- Penn State Child Cohort (PSCC) Study
Authors: Sol M Rodriguez-Colon, Fan He, Edward O Bixler, Julio Fernandez-Mendoza, Susan Calhoun, Duanping Liao
Journal: Circulation (2014)

Objective: To examine the circadian pattern of cardiac autonomic modulation (CAM) and its correlates in a population-based sample of adolescents. Methods: We used the data from 400 adolescents who completed the follow up exam in the PSCC study. CAM was assessed by heart rate variability (HRV) analysis of beat-to-beat normal R-R intervals from a 24-hour (7:00 PM to 7:00 PM) ECG, on a 30-minute basis (48 segments/person). The HRV indices included frequency domain: [high and low frequency powers (HF, LF), and LF/HF ratio] and time domain: [standard deviation of normal RRs (SDNN), and the square root of the mean squared difference of successive normal RRs (RMSSD), and heart rate (HR)]. We used a cosine periodic model to estimate each participant’s circadian parameters: mean (M), amplitude (Â), and crescent time (θ). We then used mixed-effects models to calculate group level circadian pattern as the overall M, Â of the oscillation, and θ of the highest oscillation. Results: The mean age was 16.9 yrs (SD=2.2), with 54% male and 77% white. The mean BMI percentile is 61, with 16% were obese (BMI percentile ≥ 95). Overall, the parasympathetic modulation gradually increases from late afternoon throughout the evening, and reaches the peak amplitude around 3:00 AM, at which it gradually decrease throughout most of the daytime until late afternoon. The age, sex and race showed varying differences on the CAM circadian parameters. In contrast, obesity in adolescents had adverse effects on all three circadian parameters. Using HF (a reliable index of parasympathetic modulation) as an example, the circadian pattern of the entire sample, and stratified by obesity are shown in Figure 1. Conclusion: Circadian pattern of CAM can be quantified by three cosine parameters (M, Â, and θ). Obesity in adolescents is already associated with a CAM profile indicative of sympathetic overflow and reduced parasympathetic modulation, at all levels of the CAM circadian rhythm.
Predicting prostate-cancer-specific death: Is it in the cancer?
Authors: G. E. Ayala, B. J. Miles, C. T. Freund, R. Li, A. Frolov, M. M. Ittmann, D. Kadmon, P. T. Scardino, T. Wheeler, D. Rowley
Journal: Journal of Clinical Oncology (2010)

4500 Background: Few resources exist with the ability to study tissue biomarkers and predict prostate cancer specific mortality. In this study we use a retrospective cohort with full clinicopathologic characterization, over 15 years of follow-up and biomarker studies performed over 10 years. Methods: From this cohort we built a tissue microarray (TMA) (640 patients) and immunostained markers of important prostate cancer (PCa) pathways. Analysis was perfomed in PCa, non-neoplastic and benign prostatic hyperplasia tissue using a standardized method. Slides were digitized, and quantified using an expression index (Intensity*Percentage) for nuclear/cytoplasmic expression and phosphorylated versus inactive forms. The list of biomarkers included: markers of proliferation (Ki-67) and apoptosis (TUNNEL and Caspase-3); survival pathways (AKT, SKP-2, GSK, FHKR, p27, PTEN, PIM2, C-MYC, FRAT, PKC and NFkB); hormonal regulation: DAX1, AR, ER, REG Gamma and SRC 1, 2, and 3. Stroma was represented through reactive stroma grading (RSG), perineural invasion (PNI) diameter, stromal caveolin, FGF4, and ps20. Other biomarkers were also included. A total of over 250 variables were analyzed. Results: An initial multivariate model of clinico-pathologic parameters showed that seminal vesicle invasion and Gleason score were significant predictors of PCa specific death. When all other biomarker variables were introduced into the model only 3 were independently predictive of PCa specific death: reactive stroma grading, PNI diameter percentage and REG gamma in non neoplastic tissues. No cancer markers were significant. Conclusions: This is the first study to introduce large number of tissue-based biomarkers in the study of prostate cancer specific death. Results suggest that the tumor microenvironment is critical in the determination of patients that will die of prostate cancer. It substantiates previous basic studies that indicate that the microenvironment, either as stroma or nerves, is pro-tumorigenic. We hypothesize that this might represent genetic variability in the host, which might regulate the ability of host response. The ability of predicting prostate cancer specific death might lie in the study of the host and its response, and not the cancer. No significant financial relationships to disclose.
Donor lymphocyte infusions from Ad-sig-TAA/ecdCD40L vector prime-TAA/ecdCD40L protein boost (VPP) vaccinated allodonors decrease tumor cell growth post allograft
Authors: A. B. Deisseroth, Y. Tang, H. Akbulut, J. Maynard, L. Petersen
Journal: Journal of Clinical Oncology (2007)

3071 Background: Individuals of advanced chronological age exhibit an impaired immune response to vaccines. This may be due to a reduction in the ratio of antigen naïve/memory CD4 and CD8 T cells and acquisition of functional defects in activated “helper” CD4 T cells (eg diminished CD40 ligand (CD40L) expression) during the aging process. Methods: In order to circumvent this defective response to vaccines in individuals in the fifth and sixth decades of life, our laboratory has developed an adenoviral vector (Ad-sig- TAA/ecdCD40L) vaccine which is designed for the in vivo target associated antigen (TAA) loading and activation of dendritic cells (DCs), and to overcome the absence of CD40L expression in activated CD4 helper T cells in older individuals. Results: The subcutaneous (sc) injection of this vector leads to the release of a fusion protein composed of a TAA linked to the extracellular domain (ecd) of the CD40 ligand (CD40L), which binds to the CD40 receptor on DCs, activates the DCs, and leads to the presentation of TAA fragments on Class I MHC. Two sc injections of the TAA/ecdCD40L protein as a booster following the sc administration of the Ad-sig-TAA/ecdCD40L vector (VPP) expands the magnitude of the cellular and humoral immune response induced by the vector in 18 month old aged mice as well as in younger mice. This vaccine decreased levels of negative regulatory CD4 FOXP3 T cells in tumor nodules. We administered TBI and an allogeneic stem cell transplant 7 days post sc injection of the E7 positive TC-1 cells. DLI from an Ad-sig-E7/ecdCD40L vector prime-E7/ecdCD40L protein boost vaccinated donor were injected iv 3 days post transplant, and a single E7/ecdCD40L protein boost sc vaccination one week thereafter. We found that the growth rate of the E7 positive TC-1 tumor cells post allograft was less in the vaccinated than in the control (injection of tumor cells followed in 7 days by TBI), or the animals in which the allograft recipient was vaccinated without DLI. Conclusions: Thus, the use of DLI from VPP vaccinated allodonors decreased tumor cell growth post allograft. No significant financial relationships to disclose.
Pharmacokinetics of fractionated cyclophosphamide (CY) in children with recurrent malignancies
Authors: P. Leavey, D. C. Bowers, V. M. Aquino, R. O. Bash, G. Tomlinson, T. Hofman, J. Griener, W. H. Frawley, N. J. Winick
Journal: Journal of Clinical Oncology (2005)

8533 Background: CY is an inactive pro-drug that requires hepatic biotransformation into its primary cytotoxic metabolite, 4-hydroxycyclophosphamide (HCY). The fractionated CY (FCY) schedule described is clinically relevant with a reported 59% response rate in advanced or refractory solid tumors. Because of proposed CY metabolic auto-induction it was hypothesized that the sum of the areas-under-the-curve (AUCs) of HCY for the FCY schedule would exceed the AUC of the standard (SCY) schedule, and that the sum of the 24-hour urinary CY recovery would be less with FCY than SCY. Methods: Patients received FCY x 1 [CY 500 mg/m2/day x 5 days plus etoposide 100 mg/m2/day x 5 days] and SCY x 1 [CY 2.5 g/m2/day x 1 plus etoposide 100 mg/m2/day x 5 days], each given 3 weeks apart. Patients were randomized to receive FCY as the first or second course. Courses were followed by G-CSF (5 micorgrams/kg/day). Serum samples drawn at hours 0, 0.5, 1, 3, 6, 8 and 24 after CY administration, were analyzed for HCY by HPLC with detection by UV-vis. Urine samples were analyzed for CY by HPLC with detection by electrospray ionization mass spectrometry. Results: 19 patients, 1–21 years of age, with recurrent solid tumors and leukemia were enrolled. Samples for one patient were misplaced, two patients did not complete the second cycle of therapy, one due to progressive disease and one who had an amputation for local tumor control of an epithelioid sarcoma and one patient did not have complete CY analysis. No effect was noted for the randomization of courses. Mean FCY urinary CY concentrations were lower than mean SCY (0.35±0.06 vs. 0.68±0.16 microM/ml; p = .03; n=15). Mean FCY HCY AUC was higher than mean SCY AUC (88±31 vs. 31.2±6 microM; p = .07; n=16). Patients received G-CSF after 32 courses (89%). Bone marrow suppression was notable with 81% grade 3 or 4 leucopenia (84% SCY, 77% FCY) and 28% grade 3 or 4 thrombocytopenia (37% SCY, 18% SCY). Hospitalization for fever and neutropenia occurred after 11 courses (7 SCY/4 FCY). No other significant toxicity occurred. Conclusions: We conclude that fractionated cyclophosphamide allows greater exposure to its active metabolite and this regimen should be evaluated in frontline therapies for pediatric cancers responsive to CY. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen
High-dose ifosfamide, carboplatin and etoposide (HD-ICE) with peripheral blood stem cell transfusion (PBSCT) for limited stage small-cell lung cancer (LD-SCLC)
Authors: N. Katakami, T. Nishimura, Y. Higashi, R. Seo, M. Kubota, R. Naya, M. Hayashi, A. Ikeda, K. Tomii, K. Ishihara
Journal: Journal of Clinical Oncology (2006)

7090 Background: Efficacy of high dose chemotherapy with autologous PBSCT has been demonstrated in the treatment of lymphoma. The purpose of this trial is to determine progression-free survival and long-term survival for LD-SCLC patients (pts) who responded to first-line concurrent chemo-radiotherapy followed by HD-ICE with PBSCT. Methods: Patients (pts) with pathologically proven SCLC without malignant pleural and pericardial effusion, stage II-IIIB, ECOG-PS 0–1 were eligible. All pts were treated with cisplatin (P) 60 mg/m 2 day1 and etoposide (E) 100 mg/m 2 , days 1–3, with concurrent hyperfractionted radiotherapy initially (1.5Gy X 2/day X 15 days, total 45Gy) and then two or three cycles of chemotherapy consisted of P 60 mg/m 2 , day 1, and E 120 mg/m 2 , days 1–3, or APE (adriamycin 30 mg/m 2 , day 1, P 60 mg/m 2 , day1 and E 100 mg/m 2 , days 1–3) were repeated. Pts with tumor shrinkage more than 90% after initial therapy received HD-ICE (ifosfamide 3 g/m 2 , days 1–3, carboplatin 400 mg/m 2 , days 1–3, etoposide 400 mg/m 2 , days 1–3) followed by PBSCT. All pts received prophylactic cranial irradiation (1.5 Gy × 2/day × 9 days, total 27 Gy). Results: Between 1996 and 2001, 15 pts were eligible and all 15 pts received HD-ICE with PBSCT. Patient characteristics included M/F:14/1, median age: 55 (47–62), PS 0/1: 7/8 stage IIIA/IIIB: 7/8. Grade IV neutropenia and thorombocytopenia were observed in all pts and 93% of pts experienced neutropenic fever after HD-ICE. There was no toxic death. Median follow up time was 83.2 months. Median progression free survival time was 10. 7 months and overall median survival time (MST) was 30.9 months. Two, 3 and 5-year survival rates after initial chemoradiotherapy were 67%, 33%, 25%, respectively. Conclusion: HD-ICE with PBSCT for LD-SCLC revealed promising MST and a 5-year survival rate with manageable treatment-related toxicity. A randomized phase III study comparing chemo-radiotherapy followed by HD-ICE with PBSCT to standard chemo-radiotherapy for LD-SCLC is ongoing. No significant financial relationships to disclose.
Left Ventricular Dysfunction Following Angioplasty is Related to Constriction of Capacitance and Resistance Vessels
Authors: I. Marco, L. Gregorini, J. Marco, M. Kozàkovà, Carlo Palombo, G. Anguissola, M. Bernies, I. Bossi, J. Fajadet
Journal: Journal of the American College of Cardiology (1998)
Proteomics in mammary cancer research
Authors: A. Fink-Retter, D. Gschwantler-Kaulich, C. Singer, G. Hudelist, K. Pischinger, M. Manavi, K. Czerwenka
Journal: Journal of Clinical Oncology (2008)

22206 Background: This study combines a summary of proteomics techniques and protein analysis in mammary cancer with a report of expressed and up-regulated proteins in 10 benign mammary tissues and 16 patients with mammary invasive ductal carcinoma. Till now, only few reports of proteomic research for mammary cancer could be found, including the techniques of two-dimensional gel electrophoresis (2- DE), MALDI/ESI/TOF and ESI/MS. Human carcinoma cell lines, mouse material or human serum were the most exercised materials for these studies. Only a few of them used native tissues from patients with mammary carcinomas. Methods: The aim of this study was to search for more, not well-established (up-regulated) proteins in mammary cancer in the mean and low molecular weight (MW) range, to figure out the role of post-translational modification in biologic processes and to recognize newer pathways. Results: Beside hypothetical proteins a number of transcription factors, such as zinc finger proteins (ZNFs), and not well-investigated (high significant) proteins, e.g., elongation factor 1-alpha 1 (eEF1A1), were identified by mass spectrometry (MS). eEF1A1, expressed in the membrane of mammary carcinomas, is involved in gene expression/translational elongation and has a GTPase activity and an oncogenic potency. Another protein, for example, calgizzarin (S100A11; S10AB human), which is involved in carcinoma invasion and tumor metastases, could be determined as over-expressed in the cytosol of mammary cancer tissues. It is also concerned with the regulation of numerous cellular processes such as cell cycle progression and differentiation. Conclusions: With this study, we want to demonstrate that proteome analyses provide a powerful tool for detecting potential and new biomarkers, which could be validated for diagnostic and clinical features of mammary carcinomas. No significant financial relationships to disclose.
Anti-Tumor Activity of Alectinib in Crizotinib Pre-Treated Alk-Rearranged Nsclc in Jp28927 Study
Authors: T. Seto, T. Hida, K. Nakagawa, M. Satouchi, M. Nishio, K. Hotta, H. Murakami, Y. Ohe, K. Takeda, M. Tatsuno, T. Shimada, T. Tanaka, T. Tamura
Journal: Annals of Oncology (2014)
Risk of neutropenic complications based on a prospective nationwide registry of cancer patients initiating systematic chemotherapy
Authors: D. A. Wolff, J. Crawford, D. C. Dale, M. S. Poniewierski, G. H. Lyman
Journal: Journal of Clinical Oncology (2004)

6125 Background: Myelosuppression represents the major dose-limiting toxicity of cancer chemotherapy. A prospective, nationwide study was undertaken to define risk factors for neutropenic complications (NC) and to develop risk models for selecting patients for hematopoietic support. Methods: More than 2,500 patients have been prospectively registered at 137 randomly selected practice sites. Primary outcomes included documented severe neutropenia (SN) (ANC<500), NC ( fever/ infection/other) and severe neutropenic events (SNE) (SN or NC). Results: This preliminary analysis is based on the first 2,222 patients treated to date including 886 (40%) age ≥ 65. One-third did not receive at least four cycles of chemotherapy due to disease progression (55%), refusal (11%), death (11%) and unknown (23%). Neutropenia (ANC <1000) was documented in 40% including SN in 26%. More than one-half of all initial events occurred during cycle 1. In addition to cancer and regimen type, significant predictors of SN included gender (.001), baseline neutrophils (.01), diabetes (.037) and chronic lung disease (.001). Significant predictors of NC included gender (.004) and stage (.04). In addition to cancer and regimen type, significant predictors of SNE included gender (.006), stage (.007) and COPD (.029). The risk of SNE in all cycles (1st cycle) includes: breast: 49(36); lung 31(20); lymphoma 42(33); ovary 37(17); colon 18(8). Conclusions: NC and SNE occur early in the course of therapy potentially compromising chemotherapy dose intensity and clinical outcomes. Significant independent risk factors include cancer type, regimen, dose intensity, gender, stage and several comorbidities. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Inc. Amgen, Inc. Amgen, Inc.
Abstract 109: Gender Differences in the Incidence, Risk Profiles and Outcome of In-Hospital Cardiac Arrest: A 20-Year Experience From a Middle-Eastern Country (1991-2010)
Authors: Amar M Salam, Hajar A AlBinali, Rajvir Singh, Awad Al-Qahtani, Jassim Al Suwaidi
Journal: Circulation (2013)

Objectives:  Little is known about in-hospital cardiac arrest (IHCA) in the developing countries. In this study we examined gender differences in the incidence, risk profiles and outcome of in-hospital cardiac arrest using a 20-year national cardiology registry in a Middle-Eastern Country.   Methods:  Retrospective analysis of all patients that developed IHCA in Qatar from 1991 through 2010 was made. Patients were divided into two groups according to gender. Clinical characteristics, management and outcomes were analyzed.   Results:  During the 20-years period 41,436 patients were hospitalized to the cardiology service in Qatar from 1991 to end of 2010; 9756 women and 31680 men. Of these 1684 patients developed IHCA during hospitalization; 496 women (5.1%) and 1188 men (3.8%), p    Conclusions:  Our study demonstrates that in our region women have a higher incidence of IHCA compared to men. These women had more prevalent cardiovascular co-morbidities. Our study highlights the need to study gender differences in IHCA among other ethnicities.
Phylogenetic analysis of cichlid fishes using nuclear DNA markers.
Authors: H Sültmann, W E Mayer, F Figueroa, H Tichy, J Klein
Journal: Molecular Biology and Evolution (1995)

The recent explosive adaptive radiation of cichlids in the great lakes of Africa has attracted the attention of both morphologists and molecular biologists. To decipher the phylogenetic relationships among the various taxa within the family Cichlidae is a prerequisite for answering some fundamental questions about the nature of the speciation process. In the present study, we used the random amplification of polymorphic DNA (RAPD) technique to obtain sequence differences between selected cichlid species. We then designed specific primers based on these sequences and used them to amplify template DNA from a large number of species by the polymerase chain reaction (PCR). We sequenced the amplified products and searched the sequences for indels and shared substitutions. We identified a number of such characters at three loci--DXTU1, DXTU2, and DXTU3--and used them for phylogenetic and cladistic analysis of the relationships among the various cichlid groups. Our studies assign an outgroup position to Neotropical cichlids in relation to African cichlids, provide evidence for a sister-group relationship of tilapiines to the haplochromines, group Cyphotilapia frontosa with the lamprologines of Lake Tanganyika, place Astatoreochromis alluaudi to an outgroup position with respect to other haplochromines of Lakes Victoria and Malawi, and provide additional support for the monophyly of the remaining Lake Victoria haplochromines and the Lake Malawi haplochromines. The described approach holds great promise for further resolution of cichlid phylogeny.
The sequelae and nonsequelae of conjugal bereavement
Authors: P J Clayton
Journal: American Journal of Psychiatry (1979)

The author reviews prospective studies of bereavement, which show that widows and widowers suffer from significant depressive symptoms in the first year. Young widows and widowers may have more physical distress and take more drugs. There are few changes among older men and women in physical health, visits to physicians, and hospitalizations. Psychiatric consultation and hospitalization are rare and tend to occur early in a bereavement rather than later. There is probably an increase in mortality only among older widowers in the first year. The death of one's spouse is a psychologically stressful event; however, during the first year men and women cope with the loss with minimal morbidity and mortality.
Expression profile of 29 genes by real-time quantitative PCR (RT-QPCR) in early-stage (I-IIIA) squamous cell carcinoma of the lung (SCCL)
Authors: M. Skrzypski, E. Jassem, P. Mendez, I. Chaib, A. Szymanowska, W. Rzyman, G. Gulida, J. Jassem, M. Taron, R. Rosell
Journal: Journal of Clinical Oncology (2007)

7612 Background: 5-year survival for surgically resected SCCL patients (p) is still limited. cDNA microarray studies have identified gene expression patterns that correlate with survival. We have examined the expression pattern of 29 genes selected by these studies to test their clinical prognostic value in early-stage SCCL. Methods: From 2000 to 2004, freshly frozen primary tumor specimens were obtained at the time of surgery from 66 Polish SCCL p. Sections were taken from blocks of tumor tissue for RNA extraction, and gene expression of the 29 genes was assessed by RT-QPCR (AB7900HT) using low density arrays (LDAs, Applied Biosystems). Expression values were dichotomized using the median value as the cut-off. Results: The univariate analysis showed 10 genes with prognostic value: PH4 (P=0.01); macrophage- colony stimulating factor (CSF1) (P=0.002); EGFR (P=0.05); KIAA0974 (P=0.02); ANLN (P=0.02); carbonic anhydrase IX (CA IX) (P=0.007); VEGFC (P=0.03); neurotrophic tyrosine receptor kinase 1 (P=0.04); fibronectin (P=0.002); insulin receptor (P=0.03). In the multivariate analysis of survival, CSF1, EGFR, CA IX and tumor size emerged as significant variables ( Table ). Conclusions: Tumor cells secrete CSF1, which attracts macrophages and induce them to express EGF, which in turn binds to EGFR in tumor cells. CA IX is regulated by hypoxia and plays a role in chemoresistance. Our findings highlight the relevance of tumor size and these markers in selecting p to receive adjuvant chemo- and targeted therapy. No significant financial relationships to disclose. [Table: see text]