tbuckley/cabot-search huggingface dataset:
L-Asparaginase Causes Metabolic Reprogramming in ALL Cells
Authors: Ivana Hermanova, Karel Valis, Hana Nuskova, Meritxell Alberich-Jorda, Amaia Arruabarrena Aristorena, Sonia Fernández-Ruiz, Simona Bartova, Alena Pecinova, Daniel Kavan, Karel Fiser, Marek Kuzma, Petr Novak, Tomas Mracek, Arkaitz Carracedo, Jan Trka, Julia Starkova
Journal: Blood (2014)
Long-term efficacy and safety of androgen receptor inhibitor ODM-201 in ARADES phase I/II trial.
Authors: Christophe Massard, Karim Fizazi, Petri Bono, Robert Hugh Jones, Vesa V Kataja, Nicholas David James, Jorge A. Garcia, Andrew Protheroe, Teuvo L. J. Tammela, Tony Elliot, Heikki Joensuu, Leena Mattila, John Aspegren, Annamari Vuorela, Peter Langmuir, Mika VJ Mustonen
Journal: Journal of Clinical Oncology (2014)

5079^ Background: ODM-201, is an novel oral androgen receptor (AR) inhibitor that has shown good preclinical efficacy, and has high antitumor activity in metastatic CRPC (mCRPC) patients (pts) (Fizazi et al. 2013). Methods: We report the long-term data in CYP17i-naïve progressive mCRPC pts in the ARADES phase I/II trial and the phase II extension study, in which pts were enrolled into dose levels of 100mg bid, 200mg bid or 700mg bid. Radiographic progression was evaluated either according to RECIST 1.1 for soft tissue or defined by at least 2 new lesions in bone compared to a prior scan. Results: 69 pts had progressive mCRPC; 37 pts were chemotherapy-naïve and 32 chemotherapy-pretreated. The median age was 69 yrs (53-83 yrs). 59 pts (86%) had bone metastases and 12 (17%) had visceral metastases. The median PSA was 99 ng/mL (3-1294) and the CTC count was 5 or more CTCs per 7.5ml in 42% of the pts. Forty-six (67%) pts continued drug over 12 weeks (wks). With a median follow-up of 38 wks the median time to PSA progression was 36 (95% CI: 24–74) wks for chemotherapy-naïve pts, and 21 (95%CI: 16–28) wks for chemotherapy-pretreated pts. The median time to radiographic progression was not reached for chemotherapy-naïve (95% CI: 24–not reached), and was 32 (95% CI: 12–not reached) wks for chemotherapy-pretreated pts. Treatment related AEs occurred in 22/69 (32%) pts. Most commonly reported treatment related AEs in the trial were asthenia/fatigue 6 (9%), decreased appetite 4 (6%), arthralgia 2 (3%), back pain 2 (3%), diarrhea 2 (3%), headache 2 (3%), hot flushes 2 (3%), and myalgia 2(3%), mostly mild to moderate. Conclusions: These data are in line with 12-wk efficacy and safety data reported previously, and show high anticancer activity and favorable tolerability of ODM-201. Clinical trial information: NTC01317641; NTC01429064.
Abstract 1474: A novel oncolytic adenovirus expressing tumor microenvironment modulators that activates myeloid cells, lymphocytes and endothelial cells
Authors: Angelica Loskog, Emma Eriksson, Ioanna Milenova, Rafael Moreno, Ramon Alemany
Journal: Cancer Research (2016)

Abstract Immunotherapy is becoming a cornerstone in cancer treatment of many indications. So far, pancreatic cancer has shown little response to so called checkpoint blockade antibodies. However, animal data suggests that activating immunotherapies releases the effect of checkpoint blockade also in pancreatic cancer. The tumor microenvironment (TEM) supports the growth of the tumor cells and consists of stroma cells, fibroblasts, blood vessels and immune cells. In some tumor lesions, such as those in pancreatic cancer, the TEM is dense and comprises most of the lesion. The TEM regulates immune activity via its high content of M2 macrophages, myeloid derived suppressor cells and T regulatory cells. Further, the dysfunctional blood vessels in lesions are not optimal for recruiting lymphocytes. With these aspects in mind, LOAd703 was developed. LOAd703 is an oncolytic adenovirus carrying TEM modulators. LOAd703 was constructed from the ICOVIR system of oncolytic adenoviruses in which replication depends on a dysfunctional, hyperphosphorylated retinoblastoma pathway. The genome was further altered by removing E3-6.7K and gp19K, changing the serotype 5 fiber to a serotype 35 fiber to target CD46 expressed by most tumors, as well as by adding a CMV-driven transgene cassette with the human transgenes for TMZ-CD40L and 4-1BBL. Hence, the transgenes will be expressed in both tumor and stroma while oncolysis is initiated in the tumor cells. We demonstrate herein that LOAd703 infection of a panel of pancreatic cancer cell lines efficiently induced tumor cell death within 48-72 hrs post infection while LOAd703 infection of dendritic cells demonstrated an increased maturation of myeloid cells including dendritic cells (DCs). These DCs could in turn potently activate and promote expansion of both T- and NK cells. Further, LOAd703 infection of endothelial cells (HUVEC) induced upregulation of molecules involved in lymphocyte attachment, rolling and transmigration. In conclusion, LOAd703 is a novel oncolytic virus that targets both the tumor and its TME and a clinical trial is underway to elucidate its effect in pancreatic cancer. Citation Format: Angelica Loskog, Emma Eriksson, Ioanna Milenova, Rafael Moreno, Ramon Alemany. A novel oncolytic adenovirus expressing tumor microenvironment modulators that activates myeloid cells, lymphocytes and endothelial cells. [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 1474.
P0068 : Alcoholic etiology and insulin dependent diabetes are associated to the presence of coronary disease in cirrhotic patients with basal coronary risk
Authors: M. Romero, M.M. Salcedo, D. Rincón, A. Fernández-Yunquera, M.D. Pérez-Valderas, C. Carbonell, C. Marta, G. Clemente, R. Yotti, R Banares
Journal: Journal of Hepatology (2015)
Single-operator pancreatoscopy with electrohydraulic lithotripsy of large pancreatic duct stones in post-Whipple anatomy
Authors: Yen-I Chen, Saowanee Ngamruenphong, Yamile Haito-Chavez, Majidah Bukhari, Mouen Khashab
Journal: Endoscopy (2016)

A 61-year-old man with chronic, idiopathic pancreatitis previously treated with Whipple surgery was referred for recurrent abdominal pain and dilated main pancreatic duct (MPD) on magnetic resonance imaging. Endoscopic ultrasound (EUS) showed a 9-mm MPD with an abrupt cutoff at the level of the tail, which raised suspicion for a distal stricture and the possibility of a malignancy or main duct intraductal papillary mucinous neoplasm ([Fig. 1]).
Ministers have little choice but to keep boosting spending on NHS
Authors: Adrian O’Dowd
Journal: BMJ (2016)

The government will have little choice but to keep increasing spending on the NHS if it wants to maintain services and improve the nation’s healthcare, experts have told peers.

Witnesses from various expert health think tanks all delivered the same blunt message that, if the NHS is to survive in the long term, spending must rise rather than rely on its being funded by long term efficiency saving measures. The witnesses were speaking during an evidence session of the House of Lords committee on the long term sustainability of the NHS. During the session, held on 19 July, peers asked what needed to happen to make the health service sustainable in the long term.

Richard Murray, director of policy …
Chemotherapy-associated cardiotoxicity: Timeline of left ventricular function recovery on standard heart failure regimen.
Authors: J. K. Steiner, V. L. Beggs, G. N. Schwartz, A. T. Kono
Journal: Journal of Clinical Oncology (2010)

9161 Background: Anthracycline-based chemotherapy (CTX) is associated with multiple cardiac side effects including the development of chemotherapy related heart failure (C-RHF). With recent advances in cancer therapy, long-term effects on cardiac function are more prevalent in cancer survivors. While C-RHF was previously considered largely irreversible, studies have indicated that standard heart failure treatment can prevent, slow, and even reverse cardiotoxic consequences. However, little data exists on the effects of optimal heart failure regimens on the time course and extent of cardiac recovery. Methods: In this observational study 30 patients (23 women; mean age 58 ± 12; 50% breast cancer/50% hematologic malignancies) diagnosed with C-RHF were assessed through retrospective chart review. All patients included had no known cardiac history, an initial left ventricular ejection fraction (LVEF) greater than 50%, had received anthracycline-based CTX, subsequently developed a greater than 10% LVEF reduction, and were referred to Cardiology for clinical heart failure symptoms. Echocardiograms had been ordered routinely pre-CTX and thereafter depending on heart failure symptom development. Results: The average LVEF prior to CTX was 62.6 ± 7.3%. Left ventricular (LV) dysfunction was first diagnosed within 6 months of initiation of CTX in 6 patients, within 6-12 months in 5 patients, within 1-2 years in 5 patients, and greater than 2 years after CTX in 14 patients. LVEF decreased to an average low of 30.5 ± 12.3%. After optimal therapy for heart failure was instituted, consisting of B-blockers (100%) and angiotensin converting enzyme inhibitors (80%), LVEF recovered to a maximum of 50.2 ± 13.4% in 29 out of 30 patients. Recovery to the maximal LVEF was observed within 6 months in 15 patients, within 6-12 months in 4 patients, within 1-2 years in 5 patients, and after 2 years in 6 patients. Conclusions: Both the degree of LV dysfunction due to anthracycline-based CTX and the recovery time on an optimal heart failure regimen appear to be heterogeneous. However, our data suggest that optimal heart failure therapy may improve LVEF significantly in a majority of C-RHF patients within one year. No significant financial relationships to disclose.
Prostate-Specific Antigen Screening: Time to Change the Dominant Forces on the Pendulum
Authors: Jonathan E. Shoag, Peter N. Schlegel, Jim C. Hu
Journal: Journal of Clinical Oncology (2016)

Whether prostate-specific antigen (PSA) screening prevents men from dying of prostate cancer has been the subject of debate for decades. Rather than resolve the controversy, two major randomized trials of PSA screening, with discrepant results, only further polarized the discussion. We recently showed that PSA testing in the control arm of the major US study, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, was substantially higher than previously recognized (approximately 90%), making the trial results uninterpretable. Here, we contextualize the debate about PSA screening and highlight the broad implications of our finding for prostate cancer care. Namely, we argue that the remaining singular randomized evidence shows that PSA testing does save lives and that screening should be an evidence-based recommendation. PSA testing was widely adopted in the United States in the early 1990s on the basis of its ability to detect organ-confined prostate cancers. Although population-based screening with PSA clearly resulted in more prostate cancer diagnoses, the morbidity associated with the treatment of indolent disease and the associated costs were major concerns. Randomized controlled trials were therefore initiated in Europe and the United States to address the efficacy of PSA screening. The European study found that PSA screening reduced prostate cancer–specific mortality, whereas the US study, the PLCO Cancer Screening Trial, found no difference in prostate cancer death between the intervention and control arms. 1-3 Based
Abstract 2847: Phenyl 2-pyridyl ketoxime induces cellular senescence-like alterations via NO production in human diploid fibroblasts
Authors: Hyun-Jin Jang, Eunbi Jo, Young-Ho Chung, JunSoo Park, Sung-Jun Park, Ik-Soon Jang
Journal: Cancer Research (2016)

Abstract Phenyl-2-pyridyl ketoxime (PPKO) was found to be one of small molecules enriched in the extracellular matrix of near-senescent human diploid fibroblasts (HDFs). Treatment of young HDFs with PPKO reduced the viability of young HDFs in a dose and time-dependent manner, and resulted in senescence-associated β-galactosidase (SA-β-gal) staining and G2/M cell cycle arrest. In addition, the levels of some senescence-associated proteins, such as phosphorylated ERK1/2, caveolin-1, p53, p16ink4a, and p21waf1, were elevated in PPKO-treated cells. To monitor the effect of PPKO on cell stress responses, reactive oxygen species (ROS) production was examined by flow cytometry. After PPKO treatment, ROS levels transiently increased at 30 min but then returned to baseline at 60 min. The levels of some antioxidant enzymes, such as catalase, peroxiredoxin II, and glutathione peroxidase I, were transiently induced by PPKO treatment. SOD II levels increased gradually, whereas the SOD I and III levels were biphasic during the experimental periods after PPKO treatment. Cellular senescence induced by PPKO was suppressed by chemical antioxidants, such as N-acetylcysteine, 2,2,6,6-tetramethylpiperidinyloxy and L-buthionine-(S,R)-sulfoximine. Furthermore, PPKO increased nitric oxide (NO) production via inducible NO synthase (iNOS) in HDFs. In the presence of NOS inhibitors, such as L-NG-nitroarginine methyl ester and L-NG-monomethylarginine, PPKO-induced transient NO production and SA-β-gal staining were abrogated. Taken together, these results suggest that PPKO induces cellular senescence in association with transient ROS and NO production and the subsequent induction of senescence-associated proteins. Citation Format: Hyun-Jin Jang, Eunbi Jo, Young-Ho Chung, JunSoo Park, Sung-Jun Park, Ik-Soon Jang. Phenyl 2-pyridyl ketoxime induces cellular senescence-like alterations via NO production in human diploid fibroblasts. [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 2847.
Abstract 2023: SOX4 is essential for PTEN-mediated prostate tumorigenesis in vivo
Authors: Birdal Bilir, Adeboye O. Osunkoya, W. Guy Wiles, Soma Sannigrahi, Veronique Lefebvre, Daniel Metzger, Demetri D. Spyropoulos, W. David Martin, Carlos S. Moreno
Journal: Cancer Research (2016)

Abstract Prostate cancer is the most common cancer and the second leading cause of cancer mortality in American men, underscoring the significance of unraveling the molecular mechanisms involved in the initiation and progression of the disease. The sex-determining region Y-box 4 (SOX4) gene is overexpressed in many types of human cancers, including prostate cancer, suggesting that SOX4 plays a fundamental role in tumorigenesis. In this study, we demonstrate that SOX4 is critical for PTEN-mediated prostate cancer progression in vivo. We show that homozygous deletion of Sox4 in the adult prostate epithelium strongly inhibits tumor progression initiated by homozygous loss of the Pten tumor suppressor, demonstrating the key role of SOX4 in the development of prostate cancer. Homozygous deletion of Sox4 also reduces the activation of AKT and β-catenin in Pten-null mice, resulting in inhibition of an invasive cancer phenotype. We also show that SOX4 expression is induced by loss of PTEN, and that PI3K-AKT-mTOR signaling activity is critical for SOX4 expression, suggesting a positive feedback loop between SOX4 protein and PI3K-AKT-mTOR activity. Our findings indicate that SOX4 is a critical component of the PTEN-PI3K-AKT pathway in prostate cancer, suggesting that SOX4 may be a promising molecular target for novel combinatorial therapies for both primary and advanced prostate cancers. Citation Format: Birdal Bilir, Adeboye O. Osunkoya, W. Guy Wiles, Soma Sannigrahi, Veronique Lefebvre, Daniel Metzger, Demetri D. Spyropoulos, W. David Martin, Carlos S. Moreno. SOX4 is essential for PTEN-mediated prostate tumorigenesis in vivo. [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 2023.
Rapid effects of 5-methyl-tetrahydrofolic acid on endothelial function and vascular superoxide production in human coronary artery disease
Authors: C A Antoniades, C Shirodaria, P Leeson, J Lee, N Warrick, J Bendall, D Taggart, C Ratnatunga, R Pillai, K M Channon
Journal: Journal of the American College of Cardiology (2006)
Synthetic MiR-29b Mimics Potentiate Dendritic-Cell Based Immunotherapy Against Multiple Myeloma In Vitro and In Vivo
Authors: Cirino Botta, Marco Rossi, Maria Rita Pitari, Annamaria Gullà, Teresa Del Giudice, Eugenio Morelli, Eleonora Iuliano, Emanuela Altomare, Nicola Amodio, Maria Teresa Di Martino, Pierpaolo Correale, Pierosandro Tagliaferri, Pierfrancesco Tassone
Journal: Blood (2013)
Abstract 3520: Solidago virga-aurea extract induced apoptosis of breast cancer cells through FOXO3 mediated bim expression
Authors: Haesung Kim, Chea Ha Kim, Jeong-Hyeon Kim, Jeong-Min Lee, Jeong-Ho Jeon, Jae-Yong Lee
Journal: Cancer Research (2016)

Abstract Solidago virga-aurea (European goldenrod or woundwort) is an herbaceous perennial plant of the family Asteraceae. It is used for medical system with astringent, diuretic, antiseptic and homeopathic properties. And the studies about Solidago virga-aurea are in progress for the other functions. Recently, we found that Solidago virga-aurea extract induces apoptosis of breast cancer cells. MTT assay showed that cellular viability was decreased in Solidago virga-aurea extract treated MDA-MB-231 and MCF-7 breast cancer cell lines by dose and time dependent manner. And apoptotic protein, especially bim, was increased in Solidago virga-aurea extract treated MCF-7 cell line. However, anti-apoptotic protein, Bcl-xL, does not changed by Solidago virga-aurea extract. In order to find out positive regulator of bim expression, we tested whether FOXO (forkhead-box transcription factor, group O) 3a and AMPK (5’ AMP-activated protein kinase) protein expression. In immunoblot analysis showed that FOXO3a expression level was dramatically increased in Solidago virga-aurea treated MCF-7 cells without changes of AMPK expression. Moreover, immunostaining showed that Solidago virga-aurea induces co-localization of FOXO3a and bim proteins in MCF-7 and MB-231 cells. Taken together, Solidago virga-aurea induces apoptosis by FOXO3a mediated up-regulation of bim protein. The mechanisms of Solidago virga-aurea mediated FOXO3a regulation is not fully elucidated yet, but further studies about this molecular mechanism between two proteins will give some ideas for cancer therapies for certain breast cancer patients. Citation Format: Haesung Kim, Chea Ha Kim, Jeong-Hyeon Kim, Jeong-Min Lee, Jeong-Ho Jeon, Jae-Yong Lee. Solidago virga-aurea extract induced apoptosis of breast cancer cells through FOXO3 mediated bim expression. [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 3520.
Four common genetic variants increase susceptibility to prostate cancer in the Spanish population
Authors: M. Ruiz-Echarri, S. Navarrete, F. Fuertes, S. Polo, C. Velilla, A. Ferrer Alberto Saenz, B. Saez, J. Godino, A. Tres, J. I. Mayordomo
Journal: Journal of Clinical Oncology (2008)

22045 Background: Prostate cancer is the neoplasm with highest incidence in Spanish males. Epidemiology shows that familial antecedents are a significant risk factor. We aim to look for genetic variants associated to susceptibility to prostate cancer in the Spanish population. Methods: Within a multinational genome-wide association study coordinated by Decode Genetics in 3490 consenting patients diagnosed with prostate cancer and 14345 controls, Spain contributed with 456 patients y 1078 controls. >300.000 polymorphisms have been assessed with the Infinium II method (Illumina platform). Results: Four common genetic variants associated to prostate cancer have been identified. Two of them (rs 1447295 and rs 16901979A) are located in 8q24. Frequencies of these in Spain (cases/controls/relative risk/2-tailed p) are 10.3%/7.4%/1.71/0.005 y 6.6%/4.0%/1.44/0.017. In Europe, relative risks/2-tailed p are 1.79/1.1 × 10−12 y 1.60/6.4 × 10−8 respectively. Populational attributtable risk is 12%. Two other variants are located in 17q (rs4430796 and rs1859962). Frequencies of these in Spain (cases/controls/relative risk/2-tailed p) are 46.9%/45.4%/1.06/0.45 y 51.2%/47.6%/1.15/0.071. Worldwide, relative risks/2-tailed p are 1.24/2.02 × 10−7 and 1.20/2.5 × 10−10 respectively. Populational attributtable risk is 36%. The first of these two variants had been previously reported as protective for type 2 diabetes mellitus.The implications of these findings will be presented. Conclusions: Four frequent genetic variants are associated to susceptibility to prostate cancer in the Spanish population. They are involved in 47% of all cases of this neoplasm in Spain. No significant financial relationships to disclose.
P38 MAPK Inhibition Enhances PS-341 (bortezomib)-Induced Cytotoxicity Against Multiple Myeloma Cells.
Authors: Teru Hideshima, Klaus Podar, Dharminder Chauhan, Kenji Ishitsuka, Constantine Mitsiades, Yu-Tzu Tai, Makoto Hamasaki, Noopur Raje, Hiromasa Hideshima, George Schreiner, Aaron Nguyen, Tony Navas, Nikhil C. Munshi, Paul G. Richardson, Linda S. Higgins, Kenneth C. Anderson
Journal: Blood (2004)
Molecular mechanisms of hepatitis C virus–induced hepatocellular carcinoma
Authors: T. Vescovo, G. Refolo, G. Vitagliano, G.M. Fimia, M. Piacentini
Journal: Clinical Microbiology and Infection (2016)

Hepatitis C virus (HCV) is a major leading cause of hepatocellular carcinoma (HCC). HCV-induced hepatocarcinogenesis is a multistep process resulting from a combination of pathway alterations that are either caused directly by viral factors or immune mediated as a consequence of a chronic state of inflammation. Host genetic variation is now emerging as an additional element that contribute to increase the risk of developing HCC. The advent of direct-acting antiviral agents foresees a rapid decline of HCC rate in HCV patients. However, a full understanding of the HCV-mediated tumourigenic process is required to elucidate if pro-oncogenic signatures may persist after virus clearance, and to identify novel tools for HCC prevention and therapy. In this review, we summarize the current knowledge of the molecular mechanisms responsible for HCV-induced hepatocarcinogenesis.