tbuckley/cabot-search huggingface dataset:
Growth suppressive effect of phenethyl isothiocyanate against human prostate cancer cells involves caspase mediated apoptosis and G2/M phase cell cycle arrest
Authors: Yan Zeng, Dong Xiao, Sanjay K. Srivastava, Shivendra V. Singh
Journal: Cancer Research (2004)

1370   Phenethyl isothiocyanate (PEITC), a constituent of cruciferous vegetables, has exhibited impressive activity against chemically induced cancer in experimental animals. Evidence is also mounting to indicate that PEITC (Ph-CH 2 -CH 2 -N=C=S) can inhibit proliferation of cancer cells in culture. The present studies were undertaken to gain insights into the molecular mechanism for antiproliferative effect of PEITC using PC-3 human prostate cancer cells as a model. Choice of PC-3 cells was based on epidemiological data indicating an inverse correlation between dietary intake of cruciferous vegetables and the risk for prostate cancer. We found that the viability of PC-3 cells was reduced significantly in the presence of PEITC in a concentration- and time-dependent manner with an IC 50  of about 5-7 μM following a 24 h exposure. In contrast, phenyl isothiocyanate (PITC), which is a close structural analog of PEITC but lacks the –CH 2  spacers that link the aromatic ring to N=C=S moiety, did not result in significant killing of PC-3 cells. Treatment of PC-3 cells with PEITC, but not PITC, resulted in dose-dependent apoptosis induction that was characterized by appearance of cells with sub-G0/G1 DNA content and generation of cytoplasmic histone associated DNA fragments. Time course studies using 10 μM PEITC indicated cleavage of procaspase-3 and poly(ADP-ribose)polymerase (PARP) at 16 and 24 h time points. Similar treatment of PC-3 cells with PITC failed to cause cleavage of procaspase-3 or PARP. In addition, PEITC, but not PITC, treated cells exhibited cleavage of procaspase-9 and procaspase-8. The PEITC induced apoptosis was associated with a significant decrease in the expression of Bcl-2 and Bcl-xL, but the expression of Bax was not affected by either PITC or PEITC. Dose-dependent arrest of cells in the G2/M phase was also observed in PEITC, but not PITC, treated PC-3 cultures that was associated with a significant decline in the expression of Cdc25C phosphatase and Cdk1, which play critical roles in regulation of G2/M progression. For instance, the expression of Cdc25C was reduced by >80% following a 4 h exposure to 10 μM PEITC. Expression of Cdc25B or cyclinB1 was not significantly altered in PITC or PEITC treated cells. These results indicate that subtle changes in ITC structure could have a significant impact on its anticancer activity, and that the mechanism for growth suppressive effect of PEITC involves caspase mediated apoptosis and cell cycle arrest due to down-regulation of key G2/M regulators. This investigation was supported by USPHS grant CA101753, awarded by the National Cancer Institute.
Abstract 270: The Core Function of Calcineurin
Authors: Oliver Ritter, Martin Czolbe, Lea Seidelmayer, Peter Nordbeck, Tatjana Williams
Journal: Circulation Research (2012)

Background: Recent evidence demonstrates that not only NFAT, but also calcineurin is translocated into the nucleus upon hypertrophic stimulation. Previously it was also demonstrated that calpain-mediated degradation caused a constitutive active calcineurin. We hypothesised that nuclear calcineurin is an intranuclear Ca 2+ sensor hypertrophied myocardium and that inhibition of nuclear translocation of calcineurin is a therapeutic strategy to prevent hypertrophy. Methods: Employing a transgene mouse model with conditional calpastatin overexpression (”tet-off”, resulting in calpain inhibition), different adenoviral calcineurin mutants and confocal microscopy in isolated adult cardiac myocytes we investigated calcineurin translocation and nuclear Ca 2+ transients. Assessment of cardiac function if transgenic animals was performed by 7T MRI. Results: We could demonstrate that chronic Ang II stimulation of mice caused calpain-mediated degradation of calcineurin resulting in a constitutive active calcineurin with nuclear translocation. The constitutive active calcineurin in the nucleus escaped further degradation by the UPS and sustained an ongoing hypertrophic response, even after removal of Ang II. Inhibition of nuclear translocation of activated calcineurin by a small inhibitory peptide prevented myocardial hypertrophy in vivo. Transgenic inhibition of calpain activity by calpastatin overexpression prevented proteolysis of calcineurin and allowed for relocation of calcineurin from the nucleus back to the cytosol and regression hypertrophy after removal of Ang II. We were also able to demonstrate that Ang II increases nuclear Ca 2+ transients via InsP3 receptors and that calcineurin is able to act as nuclear Ca 2+ sensor detecting local Ca 2+ release from the nuclear envelope via InsP3R. Nuclear calcineurin mutants that are defective for Ca 2+ activation failed to activate NFAT dependent transcription. Conclusion: This provides an explanation how Ca 2+ and calcineurin can regulate transcription in cardiomyocytes in response to neurohumoral signals apart from Ca 2+ changes in contraction regulation.
Patterns of recurrence after complete pathologic response to neoadjuvant chemoradiation in esophageal carcinoma: Report from northeast of Iran
Authors: Ali Taghizadeh, Mona Joudi, Alexander Heriot, Mohsen Aliakbarian, Ehsan Soltani, Reza Bagheri, Elahe Aghel
Journal: Annals of Oncology (2017)
Carfilzomib resistance due to ABCB1/MDR1 overexpression is overcome by nelfinavir and lopinavir in multiple myeloma
Authors: A Besse, S C Stolze, L Rasche, N Weinhold, G J Morgan, M Kraus, J Bader, H S Overkleeft, L Besse, C Driessen
Journal: Leukemia (2017)

Proteasome inhibitor (PI) carfilzomib (CFZ) has activity superior to bortezomib (BTZ) and is increasingly incorporated in multiple myeloma (MM) frontline therapy and relapsed settings. Most MM patients ultimately experience PI-refractory disease, an unmet medical need with poorly understood biology and dismal outcome. Pharmacologic targeting of ABCB1 improved patient outcomes, including MM, but suffered from adverse drug effects and insufficient plasma concentrations. Proteomics analysis identified ABCB1 overexpression as the most significant change in CFZ-resistant MM cells. We addressed the functional role of ABCB1 overexpression in MM and observed significantly upregulated ABCB1 in peripheral blood malignant plasma cells (PCs) vs untreated patients' bone marrow PC. ABCB1 overexpression reduces the proteasome-inhibiting activity of CFZ due to drug efflux, in contrast to BTZ. Likewise, the cytotoxicity of established anti-MM drugs was significantly reduced in ABCB1-expressing MM cells. In search for potential drugs targeting ABCB1 in clinical trials, we identified the HIV protease inhibitors nelfinavir (NFV) and lopinavir (LPV) as potent functional modulators of ABCB1-mediated drug export, most likely via modulation of mitochondria permeability transition pore. NFV and LPV restored CFZ activity at therapeutically relevant drug levels and thus represent ready-to-use drugs to be tested in clinical trials to target ABCB1 and to re-sensitize PC to established myeloma drugs, in particular CFZ.
Limits of Accuracy in Experimental Carcinogenesis as Exemplified by Tumor Induction With Ultraviolet Radiation
Authors: Harold F. Blum, Hugh G. Grady, John S. Kirby-Smith
Journal: JNCI Journal of the National Cancer Institute (1942)

Journal Article Limits of Accuracy in Experimental Carcinogenesis as Exemplified by Tumor Induction With Ultraviolet Radiation Get access Harold F. Blum, Harold F. Blum senior pharmacologist Search for other works by this author on: Oxford Academic PubMed Google Scholar Hugh G. Grady, Hugh G. Grady acting assistant surgeon Search for other works by this author on: Oxford Academic PubMed Google Scholar John S. Kirby-Smith John S. Kirby-Smith assistant physicist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 1, August 1942, Pages 83–89, https://doi.org/10.1093/jnci/3.1.83 Published: 01 August 1942
Elevated levels of circulating osteopontin are associated with a poor survival after resection of cholangiocarcinoma
Authors: Sven H. Loosen, Christoph Roderburg, Katja L. Kauertz, Inês Pombeiro, Catherine Leyh, Fabian Benz, Mihael Vucur, Thomas Longerich, Alexander Koch, Till Braunschweig, Tom F. Ulmer, Christoph Heidenhain, Frank Tacke, Marcel Binnebösel, Maximilian Schmeding, Christian Trautwein, Ulf P. Neumann, Tom Luedde
Journal: Journal of Hepatology (2017)
Decitabine As Salvage Therapy for Relapse of AML and MDS after Allogeneic Stem Cell Transplantation - a Retrospective Multicenter Analysis on Behalf of the German Cooperative Transplant Study Group
Authors: Thomas Schroeder, Christina Rautenberg, William Hermann Krüger, Uwe Platzbecker, Gesine Bug, Steinmann Juliane, Stefan A. Klein, Olaf Hopfer, Kathrin Nachtkamp, Ariane Dienst, Mustafa Kondakci, Pia Verena Schmidt, Claudia Heyn, Rainer Haas, Ulrich Germing, Martin Bornhäuser, Guido Kobbe
Journal: Blood (2016)
Abstract 080: Eya4 Induces Hypertrophy Via Regulation Of p27kip1
Authors: Tatjana Williams, Moritz Hundertmark, Peter Nordbeck, Sabine Voll, Melanie Muehlfelder, Susanna Schraut, Ines Elsner, Jost Schoenberger, Oliver Ritter
Journal: Circulation Research (2013)

Introduction: E193, a truncating mutation in the transcription cofactor Eyes absent 4 (Eya4) causes hearing impairment followed by heart failure. Here we identified the Eya4 dependent molecular mechanisms leading to the cardiac phenotype in the E193 mutation. Methods and Results: First we showed in vitro that the cyclin-dependent kinase inhibitor protein p27kip1 is a direct target of Eya4/Six1 and is suppressed upon Eya4 overexpression, whereas E193 has a dominant negative effect, releasing Eya4 mediated suppression of p27. We next generated transgenic mice with cardiac specific constitutive overexpression of full-length Eya4 or the mutant form E193. While E193 transgenic mice developed age-dependent DCM, Eya4 mice displayed cardiac hypertrophy already under basal conditions as judged by increases in heart weight and cardiomyocyte cross-sectional areas along with increases in myocardial dimension and mass. These two distinct cardiac phenotypes were even more aggravated upon pressure overload suggesting Eya4 is a regulator of cardiac hypertrophy. We also observed that the activity of Casein Kinase 2-α and the phosphorylation status of HDAC2 were significantly upregulated in the Eya4 transgenic mice, while they were significantly reduced in E193 mice, under baseline conditions and pressure overload. We were also able to identify a new human mutation (E215) with a phenotype comparable to the one seen in E193 patients. Conclusion: Our results implicate that Eya4/Six1 regulates cardiac hypertrophic reactions via p27/CK2-α/HDAC2 and indicate that truncating mutations in Eya4 interfere with this newly established signalling pathway.
Updated overall survival (OS) analysis from the international, phase 3, randomized, placebo-controlled RESORCE trial of regorafenib for patients with hepatocellular carcinoma (HCC) who progressed on sorafenib treatment
Authors: Jordi Bruix, Philippe Merle, Alessandro Granito, Yi-Hsiang Huang, Gyorgy Bodoky, Osamu Yokosuka, Olivier Rosmorduc, Valeriy Breder, Rene Gerolami, Gianluca Masi, Paul J. Ross, Shukui Qin, Tianqiang Song, Jean-Pierre Bronowicki, Isabelle Ollivier-Hourmand, Masatoshi Kudo, Marie-Aude LeBerre, Annette Baumhauer, Gerold Meinhardt, Guohong Han
Journal: Annals of Oncology (2017)
Lower Rates of Influenza Infection Following Two Dose Series of High Dose Vaccination in Plasma Cell Disorders: Results of a Randomized, Double-Blind, Placebo-Assisted Clinical Trial
Authors: Andrew R Branagan, Eamon Duffy, Terri L Parker, Stuart Seropian, Connor Foster, Lin Zhang, Rakesh Verma, Daniel Zelterman, Geliang Gan, Debra S. Brandt, Jeremy Kortmansky, David H Witt, Thomas M Ferencz, Madhav V Dhodapkar
Journal: Blood (2016)
TP53INP1 Downregulation Activates a p73-Dependent DUSP10/ERK Signaling Pathway to Promote Metastasis of Hepatocellular Carcinoma
Authors: Kai-Yu Ng, Lok-Hei Chan, Stella Chai, Man Tong, Xin-Yuan Guan, Nikki P Lee, Yunfei Yuan, Dan Xie, Terence K Lee, Nelson J Dusetti, Alice Carrier, Stephanie Ma
Journal: Cancer Research (2017)

Identifying critical factors involved in the metastatic progression of hepatocellular carcinoma (HCC) may offer important therapeutic opportunities. Here, we report that the proapoptotic stress response factor TP53INP1 is often selectively downregulated in advanced stage IV and metastatic human HCC tumors. Mechanistic investigations revealed that TP53INP1 downregulation in early-stage HCC cells promoted metastasis via DUSP10 phosphatase-mediated activation of the ERK pathway. The DUSP10 promoter included putative binding sites for p73 directly implicated in modulation by TP53INP1. Overall, our findings show how TP53INP1 plays a critical role in limiting the progression of early-stage HCC, with implications for developing new therapeutic strategies to attack metastatic HCC. Cancer Res; 77(17); 4602-12. ©2017 AACR.
Clinical usefulness of mtTFA expression as a predictive marker in colorectal cancer patients treated with FOLFOX
Authors: Y. Yoshida, J. Hasegawa, R. Nezu, Y. Kim, M. Hirota, K. Yoshikawa, K. Kawano, H. Izumi, K. Kohno
Journal: Journal of Clinical Oncology (2009)

4059 Background: We previously reported that mitochondrial transcription factor A (mtTFA; also designated Tfam) preferentially recognizes cisplatin-damaged DNA via physical interaction with p53 and is upregulated by the treatment with cisplatin and 5-FU (Yoshida et al, Cancer Res. 2003). The aim of this study was to evaluate whether expression of mtTFA predicts clinical outcome in patients with metastatic colorectal cancer treated with modified FOLFOX6 (mFOLFOX6). Methods: From January 2006 to April 2008, 59 patients who had metastatic lesions from colorectal cancer treated with mFOLFOX6 at the Osaka Rosai Hospital were included in this study. They consisted of 25 women (42.4%) and 34 men (57.6%), with a median age of 62 years (29–84). Patients were treated with oxaliplatin 85mg/m 2 plus leucovorin 200mg/m 2 as a 2-h infusion at day 1, followed by 5-FU bolus 400mg/m 2 and 46-h continuous infusion of 2400 mg/m 2 . Treatment was repeated in 2-week intervals for at least 4 cycles. The expressions of mtTFA and p53 of resected primary tumors were examined by immunohistochemistry. Results: Among 59 patients, one complete response and 32 partial responses were observed (response rate, 55.9%) . The positive rates was 44.1% (26/59; CR 1, PR 7, SD/PD 18) for mtTFA and 59.3% (35/59; CR 1, PR 19, SD/PD 15) for p53, respectively. Strong expression of mtTFA was detected in 8 of 33 CR/PR (24.2%) and in 18 of 26 SD/PD (69.2%), indicating that the expression of mtTFA correlated significantly with response to chemotherapy (P&lt;0.01). On the other hand, there was no significant correlation between response to chemotherapy and p53 expression (P=0.82). mtTFA expression was significantly associated with overall survival (P=0.036) and progression free survival (P=0.037). Multivariate analysis revealed that mtTFA expression significantly impacted on OS (Hazard ratio 2.10, P=0.036). Conclusions: Immunohistochemical study of mtTFA may be useful in prediction of the clinical outcome of metastatic colorectal cancer patients treated with FOLFOX. No significant financial relationships to disclose.
Peripheral blood lymphocytes subpopulations in chronic hepatitis B (CHB) infection
Authors: R MacNicholas, DG Doherty, S Norris
Journal: Endoscopy (2006)

Aims: Previous studies have shown that intrahepatic CD4 +and CD8 + T cell responses are less vigorous in individuals who develop chronic infection while intraheaptic CD56 + CD3 + (NK T) cell populations may be expanded. Our aim was to investigate the numbers and phenotypes of peripheral lymphocyte subsets in CHB patients.
Randomized Phase II Multi-Center Trial of Busulfan, Etoposide, and Cyclophosphamide Versus Busulfan, Etoposide, and Melphalan As Conditioning Therapy for Autologous Transplantation in Patients with Non-Hodgkin's Lymphoma: A Multicenter Study from Consortium for Improving Survival of Lymphoma (CISL)
Authors: Kyoung Ha Kim, Lee Jae Hoon, Mark Lee, Kim Hoon-Gu, Young Rok Do, Yong Park, Sung Yong Oh, Ho-Jin Shin, Won Seog Kim, Sung-Kyu Park, Jong-Ho Won, Jee Hyun Kong, Moo-Rim Park, Je-Jung Lee, Jae-Yong Kwak, Hye Jin Kang, Yeung-Chul Mun
Journal: Blood (2016)
Virtual Human Models for Electromagnetic Studies and Their Applications
Authors: Sergey N. Makarov, Gregory M. Noetscher, Janakinadh Yanamadala, Matthew W. Piazza, Sara Louie, Alexander Prokop, Ara Nazarian, Aapo Nummenmaa
Journal: IEEE Reviews in Biomedical Engineering (2017)

Numerical simulation of electromagnetic, thermal, and mechanical responses of the human body to different stimuli in magnetic resonance imaging safety, antenna research, electromagnetic tomography, and electromagnetic stimulation is currently limited by the availability of anatomically adequate and numerically efficient cross-platform computational models or "virtual humans." The objective of this study is to provide a comprehensive review of modern human models and body region models available in the field and their important features.
I want to break free: liberation from noninvasive ventilation
Authors: Stefano Nava, Begum Ergan
Journal: European Respiratory Journal (2017)

A lot of emphasis has been placed on the weaning process from invasive mechanical ventilation, since prolonged ventilation has been associated with increased length of intensive care unit stay, increased levels of complications and increased costs. Weaning in this respect may be considered as an "all or none" phenomenon, since the patients are abruptly removed from any form of ventilator support after extubation unless they are placed on noninvasive ventilation (NIV). In patients with acute hypercapnic respiratory failure (AHRF), particularly those with chronic obstructive pulmonary disease (COPD), the use of NIV is considered to be the first line treatment. However, no systematic studies have so far been performed in this population, except for some small observational investigations. The study by Sellares et al. [1] in this issue of the European Respiratory Journal is therefore a welcome addition to the field in order to finally shed some light on the subject. Weaning from noninvasive ventilation amongst patients with acute hypercapnic respiratory failure <http://ow.ly/o3eq30clY6o>
Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas
Authors: Alessandro Canella, Alessandra M. Welker, Ji Young Yoo, Jihong Xu, Fazly S. Abas, Divya Kesanakurti, Prabakaran Nagarajan, Christine E. Beattie, Erik P. Sulman, Joseph Liu, Joy Gumin, Frederick F. Lang, Metin N. Gurcan, Balveen Kaur, Deepa Sampath, Vinay K. Puduvalli
Journal: Clinical Cancer Research (2017)

Purpose: HSP90, a highly conserved molecular chaperone that regulates the function of several oncogenic client proteins, is altered in glioblastoma. However, HSP90 inhibitors currently in clinical trials are short-acting, have unacceptable toxicities, or are unable to cross the blood-brain barrier (BBB). We examined the efficacy of onalespib, a potent, long-acting novel HSP90 inhibitor as a single agent and in combination with temozolomide (TMZ) against gliomas in vitro and in vivoExperimental Design: The effect of onalespib on HSP90, its client proteins, and on the biology of glioma cell lines and patient-derived glioma-initiating cells (GSC) was determined. Brain and plasma pharmacokinetics of onalespib and its ability to inhibit HSP90 in vivo were assessed in non-tumor-bearing mice. Its efficacy as a single agent or in combination with TMZ was assessed in vitro and in vivo using zebrafish and patient-derived GSC xenograft mouse glioma models.Results: Onalespib-mediated HSP90 inhibition depleted several survival-promoting client proteins such as EGFR, EGFRvIII, and AKT, disrupted their downstream signaling, and decreased the proliferation, migration, angiogenesis, and survival of glioma cell lines and GSCs. Onalespib effectively crossed the BBB to inhibit HSP90 in vivo and extended survival as a single agent in zebrafish xenografts and in combination with TMZ in both zebrafish and GSC mouse xenografts.Conclusions: Our results demonstrate the long-acting effects of onalespib against gliomas in vitro and in vivo, which combined with its ability to cross the BBB support its development as a potential therapeutic agent in combination with TMZ against gliomas. Clin Cancer Res; 23(20); 6215-26. ©2017 AACR.
Central focused convolutional neural networks: Developing a data-driven model for lung nodule segmentation
Authors: Shuo Wang, Mu Zhou, Zaiyi Liu, Zhenyu Liu, Dongsheng Gu, Yali Zang, Di Dong, Olivier Gevaert, Jie Tian
Journal: Medical Image Analysis (2017)

Accurate lung nodule segmentation from computed tomography (CT) images is of great importance for image-driven lung cancer analysis. However, the heterogeneity of lung nodules and the presence of similar visual characteristics between nodules and their surroundings make it difficult for robust nodule segmentation. In this study, we propose a data-driven model, termed the Central Focused Convolutional Neural Networks (CF-CNN), to segment lung nodules from heterogeneous CT images. Our approach combines two key insights: 1) the proposed model captures a diverse set of nodule-sensitive features from both 3-D and 2-D CT images simultaneously; 2) when classifying an image voxel, the effects of its neighbor voxels can vary according to their spatial locations. We describe this phenomenon by proposing a novel central pooling layer retaining much information on voxel patch center, followed by a multi-scale patch learning strategy. Moreover, we design a weighted sampling to facilitate the model training, where training samples are selected according to their degree of segmentation difficulty. The proposed method has been extensively evaluated on the public LIDC dataset including 893 nodules and an independent dataset with 74 nodules from Guangdong General Hospital (GDGH). We showed that CF-CNN achieved superior segmentation performance with average dice scores of 82.15% and 80.02% for the two datasets respectively. Moreover, we compared our results with the inter-radiologists consistency on LIDC dataset, showing a difference in average dice score of only 1.98%.
Attainment of Complete Remission Is Significantly Associated with Longer Survival Outcomes in Relapsed/Refractory (R/R) CLL: A Meta-Analysis
Authors: Varun Ektare, Christopher P. Fox, Rod S Taylor, Inocencio J Timothy, German E Pena, Johnathan C Maher, Sonya J. Snedecor
Journal: Blood (2016)
Probe based multiphoton microscope imaging for lysosomal acidification of live colon cancer cell
Authors: Geeho Min, Min Lee Jung, Woojung Kim, Ji Choi Seong, kyung Yoo In, Han Kim Seung, Min Lee Jae, Soon Choi Hyuk, Sun Kim Eun, Bora Keum, Tae Jeen Yoon, Jai Chun Hoon, Sik Lee Hong, Duck Kim Chang, Jung-Nyoung Heo, Rae Cho Bong
Journal: Annals of Oncology (2017)
Response to: Routine usage of sentinel node biopsy in melanoma management must cease
Authors: D.B. Saleh
Journal: British Journal of Dermatology (2017)

I read with interest the communication by Dixon and colleagues. I share concern if patients are being told therapies are only available to them if they have a sentinel node biopsy (SNB). SNB does more than offer a subset of patients added prognostic information. What the MLST-1 trial emphatically demonstrated is that SNB is a useful staging tool to stratify patients. Those with a positive SNB do significantly worse than those with a negative result. Furthermore, micro-metastases in a lymph node left alone, is highly likely to become macroscopic, prompting a therapeutic lymph node dissection (TLND).

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