tbuckley/cabot-search huggingface dataset:
MR perfusion-weighted imaging in the evaluation of high-grade gliomas after treatment: a systematic review and meta-analysis
Authors: Praneil Patel, Hediyeh Baradaran, Diana Delgado, Gulce Askin, Paul Christos, Apostolos John Tsiouris, Ajay Gupta
Journal: Neuro-Oncology (2016)

Abstract Background. Distinction between tumor and treatment related changes is crucial for clinical management of patients with high-grade gliomas. Our purpose was to evaluate whether dynamic susceptibility contrast-enhanced (DSC) and dynamic contrast enhanced (DCE) perfusion-weighted imaging (PWI) metrics can effectively differentiate between recurrent tumor and posttreatment changes within the enhancing signal abnormality on conventional MRI. Methods. A comprehensive literature search was performed for studies evaluating PWI-based differentiation of recurrent tumor and posttreatment changes in patients with high-grade gliomas (World Health Organization grades III and IV). Only studies published in the “temozolomide era” beginning in 2005 were included. Summary estimates of diagnostic accuracy were obtained by using a random-effects model. Results. Of 1581 abstracts screened, 28 articles were included. The pooled sensitivities and specificities of each study's best performing parameter were 90% and 88% (95% CI: 0.85–0.94; 0.83–0.92) and 89% and 85% (95% CI: 0.78–0.96; 0.77–0.91) for DSC and DCE, respectively. The pooled sensitivities and specificities for detecting tumor recurrence using the 2 most commonly evaluated parameters, mean relative cerebral blood volume (rCBV) (threshold range, 0.9–2.15) and maximum rCBV (threshold range, 1.49–3.1), were 88% and 88% (95% CI: 0.81–0.94; 0.78–0.95) and 93% and 76% (95% CI: 0.86–0.98; 0.66–0.85), respectively. Conclusions. PWI-derived thresholds separating viable tumor from treatment changes demonstrate relatively good accuracy in individual studies. However, because of significant variability in optimal reported thresholds and other limitations in the existing body of literature, further investigation and standardization is needed before implementing any particular quantitative PWI strategy across institutions.
Neurotransmitters In The Mammalian Circadian System
Authors: B Rusak
Journal: Annual Review of Neuroscience (1990)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Abstract 1810: Heterogeneous activation of PP-1 and Akt determines AR-v7 protein expression in prostate cancer cells under AR inhibition
Authors: Yinan Li, Ning Xie, Martin E. Gleave, Paul Rennie, Xuesen Dong
Journal: Cancer Research (2016)

Abstract Background: Blocking the androgen receptor (AR) signaling is the first- and second-line treatment for metastatic prostate cancers. Although the newly developed AR pathway inhibitor (ARPI) improves patient survival, tumors invariably recurs and are most often driven by reactivation of the AR signaling. Enhanced expression of the AR splice variant, AR-v7, had been demonstrated to be one of the key mechanisms that confer prostate tumors with therapy resistance. However, molecular mechanisms by which control AR-v7 protein expression remain unclear. Experimental Design: Multiple prostate cancer lines were challenged with androgen depletion and/or Enzalutamide treatment. Protein phosphatase-1 (PP-1) and Akt kinase activation were measured. AR and AR-v7 serine phosphorylation, ubiquitination, protein degradation as well as subcellular localization were determined. Results: Enzalutamide induces differential activation of protein phosphatase-1 (PP-1) and Akt kinase depending on the genetic background of prostate cancer cell lines. PP-1 activation prevents AR-v7 from serine213 phosphorylation, Mdm2-mediated ubiquitination modification, cytoplasmic localization and proteasomal protein degradation. By contrast, Akt activation functions in the opposite to PP-1 and stimulates AR-v7 degradation. Therefore, the balance of PP-1 and Akt activations under ARPI treatment determines AR-v7 protein expression in prostate cancer cells. Conclusion: Our studies highlight the decisive roles of PP-1 and Akt for AR-v7 protein expression and activities when AR is functionally blocked. It also provides an explanation on heterogeneous AR-v7 protein expression in prostate tumor biopsies. Citation Format: Yinan Li, Ning Xie, Martin E. Gleave, Paul Rennie, Xuesen Dong. Heterogeneous activation of PP-1 and Akt determines AR-v7 protein expression in prostate cancer cells under AR inhibition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1810.
Abstract 594: Antibodies targeting LAG-3, TIM-3, KIR cloned from healthy human donors
Authors: Angeles Estelles, Robert Stephenson, Keyi Liu, Evelene Lomongsod, Da Ngyen, Jianzhong Zhzng, Yifan Yang, Manfred Heideker, Lawrence Kauvar, Stefan Ryser, Mikhail L. Gishizky
Journal: Cancer Research (2016)

Abstract The immunosurveillance/immunoediting theory postulates that tumor growth is repressed in healthy individuals through the activation of adaptive and innate immune mechanisms. The clinical success of antibodies that target inhibitory checkpoint pathways of the immune system (i.e. CTLA-4, PD-1) has provided compelling evidence in support of this theory and raises the question of whether antibodies targeting these, or other inhibitory immune cell modulators (ICM), are present in apparently healthy individuals. The present studies were designed to answer this question by probing the circulating memory B-cell compartment that represents a historic record of an individual's lifelong adaptive immune response. Methods: Blood from donors, with no known cancer history, was screened for the presence of anti-ICM binding memory B-cells targeting LAG-3, TIM-3, B7-H3, KIR, and VISTA, using Trellis's established CellSpotTM technology that can detect the presence of antigen specific memory B-cells at a frequency of 0.1 per 100,000 memory B-cells. Results: Circulating memory B-cells targeting ICM's were present in all apparently healthy individuals tested (20 total). There was substantial variation as to which ICM's were recognized within each individual across this sample population. Antibodies cloned from these rare B-cells were of IgG class and exhibited low to sub-nM affinity toward the specific ICM. These high affinity antibodies bound their respective antigens on activated T-cells and were able to augment immune stimulatory cytokine release in cellular assays. Data from ongoing studies will be presented. Conclusion: These studies demonstrate that apparently healthy individuals produce high affinity, pharmacologically active anti-ICM antibodies. Thus, healthy individuals represent a previously unrecognized source of antibodies that have undergone natural selection and hold particular promise as potential therapeutic agents for the treatment of cancer. Citation Format: Angeles Estelles, Robert Stephenson, Keyi Liu, Evelene Lomongsod, Da Ngyen, Jianzhong Zhzng, Yifan Yang, Manfred Heideker, Lawrence Kauvar, Stefan Ryser, Mikhail L. Gishizky. Antibodies targeting LAG-3, TIM-3, KIR cloned from healthy human donors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 594.
Phase III Randomized Trial of Ipilimumab Plus Etoposide and Platinum Versus Placebo Plus Etoposide and Platinum in Extensive-Stage Small-Cell Lung Cancer
Authors: Martin Reck, Alexander Luft, Aleksandra Szczesna, Libor Havel, Sang-We Kim, Wallace Akerley, Maria Catherine Pietanza, Yi-long Wu, Christoph Zielinski, Michael Thomas, Enriqueta Felip, Kathryn Gold, Leora Horn, Joachim Aerts, Kazuhiko Nakagawa, Paul Lorigan, Anne Pieters, Teresa Kong Sanchez, Justin Fairchild, David Spigel
Journal: Journal of Clinical Oncology (2016)

Purpose Patients with extensive-stage disease small-cell lung cancer (SCLC) have poor survival outcomes despite first-line chemotherapy with etoposide and platinum. This randomized, double-blind phase III study evaluated the efficacy and safety of ipilimumab or placebo plus etoposide and platinum in patients with newly diagnosed extensive-stage disease SCLC. Patients and Methods Patients were randomly assigned at a ratio of one to one to receive chemotherapy with etoposide and platinum (cisplatin or carboplatin) plus ipilimumab 10 mg/kg or placebo every 3 weeks for a total of four doses each in a phased induction schedule (chemotherapy in cycles one to four; ipilimumab or placebo beginning in cycle three up to cycle six), followed by ipilimumab or placebo maintenance every 12 weeks. Primary end point was overall survival (OS) among patients receiving at least one dose of blinded study therapy. Results Of 1,132 patients randomly assigned, 954 received at least one dose of study therapy (chemotherapy plus ipilimumab, n = 478; chemotherapy plus placebo, n = 476). Median OS was 11.0 months for chemotherapy plus ipilimumab versus 10.9 months for chemotherapy plus placebo (hazard ratio, 0.94; 95% CI, 0.81 to 1.09; P = .3775). Median progression-free survival was 4.6 months for chemotherapy plus ipilimumab versus 4.4 months for chemotherapy plus placebo (hazard ratio, 0.85; 95% CI, 0.75 to 0.97). Rates and severity of treatment-related adverse events were similar between arms, except for diarrhea, rash, and colitis, which were more frequent with chemotherapy plus ipilimumab. Rate of treatment-related discontinuation was higher with chemotherapy plus ipilimumab (18% v 2% with chemotherapy plus placebo). Five treatment-related deaths occurred with chemotherapy plus ipilimumab and two with chemotherapy plus placebo. Conclusion Addition of ipilimumab to chemotherapy did not prolong OS versus chemotherapy alone in patients with newly diagnosed extensive-stage disease SCLC. No new or unexpected adverse events were observed with chemotherapy plus ipilimumab. Several ongoing studies are evaluating ipilimumab in combination with programmed death-1 inhibitors in SCLC.
A Phase l Study of a Tumor-targeted Systemic Nanodelivery System, SGT-94, in Genitourinary Cancers
Authors: Arlene Siefker-Radtke, Xin-qiao Zhang, Charles C Guo, Yu Shen, Kathleen F Pirollo, Sharjeel Sabir, Chris Leung, Cindy Leong-Wu, Chi-Ming Ling, Esther H Chang, Randall E Millikan, William F Benedict
Journal: Molecular Therapy (2016)

Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells. SGT-94 was administered intravenously in a first-in-man study in metastatic genitourinary cancer. Minimal side effects were observed; dose-limiting toxicity (DLT) has not been reached in 11 evaluable patients. There was evidence of clinical activity at the 2.4 mg dose with one complete remission (CR) and one partial remission (PR). The patient in CR was retreated upon progression and had a second PR. Furthermore, there was tumor-specific targeting of the SGT-94 complex. One patient had wedge resections of two lung metastases which demonstrated RB94 expression at the DNA level by polymerase chain reaction (PCR) and at the protein level by Western blotting, with no RB94 present in normal contiguous lung. In conclusion, systemically delivered SGT-94 showed evidence of selective tumor targeting and was well tolerated with evidence of clinical activity. Additional studies are warranted to explore the activity of this drug as a single agent and in combination therapy. Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells. SGT-94 was administered intravenously in a first-in-man study in metastatic genitourinary cancer. Minimal side effects were observed; dose-limiting toxicity (DLT) has not been reached in 11 evaluable patients. There was evidence of clinical activity at the 2.4 mg dose with one complete remission (CR) and one partial remission (PR). The patient in CR was retreated upon progression and had a second PR. Furthermore, there was tumor-specific targeting of the SGT-94 complex. One patient had wedge resections of two lung metastases which demonstrated RB94 expression at the DNA level by polymerase chain reaction (PCR) and at the protein level by Western blotting, with no RB94 present in normal contiguous lung. In conclusion, systemically delivered SGT-94 showed evidence of selective tumor targeting and was well tolerated with evidence of clinical activity. Additional studies are warranted to explore the activity of this drug as a single agent and in combination therapy.
The attenuation system of the human brain
Authors: M. I Posner, S. E Petersen
Journal: Annual Review of Neuroscience (1990)

Illustration de trois fonctions principales qui sont predominantes dans l'etude de l'intervention de l'attention dans les processus cognitifs: 1) orientation vers des evenements sensoriels; 2) detection des signaux par processus focal; 3) maintenir la vigilance en etat d'alerte
Abstract 1942: Change in serum microRNA expression during neoadjuvant chemoradiation for rectal cancer
Authors: Stephanie H. Lim, Paul De Souza, Wei Chua, Weng Ng, Benjamin Harris, Mark J. Cowley, Kevin Spring
Journal: Cancer Research (2016)

Abstract Introduction MicroRNAs (miRNA) expression may change with treatment and influence responses in locally advanced rectal cancer (LARC) making them potentially useful predictive and prognostic biomarkers. We investigated 112 miRNAs in serum during chemoradiation for LARC. Methods Twenty-one patients with LARC treated with neoadjuvant chemoradiation were prospectively recruited for the study. Serum was collected at three time-points: 1) at diagnosis (baseline), 2) at three weeks into treatment and 3) at completion of chemoradiation (pre-surgery). Serum was also collected from 10 healthy controls. RNA extraction was performed using the Norgen™ total RNA purification kit. Reverse transcription and pre-amplification were performed as per the Taqman™ OpenArray MicroRNA Panels manufacturer's instructions. miRNA array qPCR was performed on 112 miRNA targets using the QuantStudio™ 12K platform. Differentially expressed miRNAs were identified using the delta-delta-Ct method, using the endogenous U6 snRNA as the control. Analysis was performed in R, using paired t-statistics, and the Benjamini-Hochberg False Discovery Rate for multiple hypothesis testing adjustment, with a threshold q&amp;lt;0.05 for significant differential expression. Enriched KEGG pathways were identified using DIANA, based on verified gene targets of each miRNA from Tarbase. Results We identified 12 miRNAs that were significantly differentially expressed between patients and matched controls. The strongest differences were observed between patient samples at baseline and completion of chemoradiation, where eight miRNAs decreased in expression: hsa-miR-101, hsa-miR-130a, hsa-miR-130b, hsa-miR-223, hsa-miR-27a, hsa-miR-628-5p, hsa-miR-630 and hsa-miR-720, all with fold change &amp;gt; 3-fold. These genes are known to target key rectal cancer genes such as SMAD4, BCL2, MSH2 and TGFBR2. An additional three miRNAs changed significantly between baseline and week 3: hsa-miR-135b*, hsa-miR-375 and hsa-miR-629. All except hsa-miR-135b* became less abundant. Conclusions Ten differentially expressed miRNAs appear downregulated during chemoradiation in LARC. These miRNAs have been implicated in cell proliferation, the epithelial-mesenchymal transition and radiation resistance. Further work will be undertaken to understand the functional implications of these changes. Citation Format: Stephanie H. Lim, Paul De Souza, Wei Chua, Weng Ng, Benjamin Harris, Mark J. Cowley, Kevin Spring. Change in serum microRNA expression during neoadjuvant chemoradiation for rectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1942.
Abstract LB-228: Polo-like kinase 4: A potential new target for the management of prostate cancer
Authors: Chandra K. Singh, Maria Shabbir, Minakshi Nihal, Kenneth A. Iczkowski, Nihal Ahmad
Journal: Cancer Research (2016)

Abstract Prostate cancer (PCa) is the most prevalent non-cutaneous cancer of males. According to an estimate from the American Cancer Society, it is expected that approximately 180,890 new cases of PCa will be diagnosed and 26,120 PCa-related deaths will occur in the United States in 2016. Therefore, identification of additional molecular target(s) could be useful in designing novel mechanism-based approaches for the prevention and/or therapy of PCa. PLK4 belongs to the polo-like kinase family of serine/threonine protein kinases that localizes to centrioles and regulates centriole duplication during the cell cycle. Essentially, PLK4 is a low abundance suicidal kinase that is known to auto-phosphorylate itself to promote its own destruction to limit centriole duplication once per cell cycle phase. Since centrosome aberrations are frequently seen in cancer, the central role of PLK4 in centriole duplication suggests its significance as a potential target for cancer management. However, the role and functional relevance of PLK4 in PCa development and progression has not been investigated. In this study, we determined the expression profile of PLK4 in PCa using immunohistochemical analysis of multiple tissue microarrays (TMAs) containing a variety of cancerous and benign human prostate tissues. The TMAs were immunostained for PLK4 and the images were scanned and analyzed for protein levels using Aperio ScanScope at 40x magnification. We found a significant upregulation of PLK4 in PCa, compared to benign prostatic tissues. Further, we found a significant upregulation of PLK4 protein and mRNA in human PCa cells, as assessed by western blot and qRT-PCR analyses, respectively. To further assess the relevance of PLK4 overexpression in PCa, we determined the effect of a small molecule inhibitor of PLK4, centrinone-B, on androgen-responsive 22Rν1 and androgen-independent DU145 human PCa cells. Centrinone-B treatment (0, 50, 100 and 200 nM; for 24 and 48 h) resulted in a marked decrease in growth and viability of PCa cells, as assessed i) by CytoTox-Glo™ cytotoxicity assay, and ii) microscopic evaluation of cells following staining with Nuclear Fast Red and Crystal Violet dyes. Further, centrinone-B treatment resulted in a G1 phase cell cycle arrest of human PCa cells. Taken together, our study provides first direct evidence of a pro-proliferative function of PLK4 in PCa. However, additional studies are required to ascertain the relevance of our in vitro findings to in vivo situations in relevant animal models. Citation Format: Chandra K. Singh, Maria Shabbir, Minakshi Nihal, Kenneth A. Iczkowski, Nihal Ahmad. Polo-like kinase 4: A potential new target for the management of prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-228.
Abstract 3060: The role of miR-135b in clinical outcome and metastasis in colorectal cancer
Authors: Wei-Ran Wang, Yawen Cheng, Nan-Yung Hsu Hsu
Journal: Cancer Research (2015)

Abstract Colorectal cancer (CRC) is one of the leading causes of cancer death in both the Western world and Taiwan. Age, gender, and genes are important risk factors for colorectal cancer. Activation of Wnt signaling pathway is an important step involved in the pathogenesis of colorectal cancer. Approximately 70-80% of sporadic colorectal carcinomas have somatic mutations that inactivate APC. But, only 30% CRC patients in Taiwan have APC gene mutation that was significantly lower than the other countries. Thus, the other mechanism involved in APC gene inactivation may contributed to CRC progression in Taiwan. Here, we focus on the Wnt signaling associate microRNAs. Four wnt signaling-associated microRNAs were selected in this study, including miR-21, miR-200a, miR-135a and miR-135b. A total of 156 colorectal cancer patients were enrolled in this study. The expression of miR-21, miR-200a, miR-135a, miR-135b and wnt signaling association genes were analyzed by quantitative RT-PCR and immunohistochemistry. The expression levels of miR-21, miR-200a and miR-135a were not correlated with clinical parameters of CRC patients. The expression of miR-135b were positive correlated with gender, tumor stage, and lymph node metastasis. No any significantly correlation were found between miR-135b, Wnt, β-catenin and APC. But the expression levels of miR-135b were positive correlated with the upstream gene STAT3, β-catenin and C-Myc. Thus, we suggested that upregulation of miR-135b may through β-catenin mediated STAT3 activation. Citation Format: Wei-Ran Wang, Yawen Cheng, Nan-Yung Hsu Hsu. The role of miR-135b in clinical outcome and metastasis in colorectal 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 3060. doi:10.1158/1538-7445.AM2015-3060
Development and Initial Validation of the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire (ITP-PAQ), a Disease-Specific Health-Related Quality of Life (HRQoL) Questionnaire.
Authors: Susan D. Mathias, James B. Bussel, James N. George, Robert McMillan, Gary J. Okano, Janet L. Nichol
Journal: Blood (2006)
PD3-3-8: A phase II study of continuous daily sunitinib dosing in patients with previously-treated advanced non-small cell lung cancer (NSCLC)
Authors: Giorgio V. Scagliotti, Silvia Novello, Julie R. Brahmer, Ramaswamy Govindan, Rafael Rosell, Chandra P. Belani, James N. Atkins, Lesley Tye, Richard Chao, Mark A. Socinski
Journal: Journal of Thoracic Oncology (2007)