tbuckley/cabot-search huggingface dataset:
Abstract 422: Functional analysis of family with sequence similarity 83, member B in lung adenocarcinoma
Authors: Takumi Yamaura, Naoyuki Okabe, Hironori Takagi, Yuki Owada, Takuya Inoue, Yuzuru Watanabe, Mitsuro Fukuhara, Satoshi Muto, Yuki Matsumura, Takeo Hasegawa, Atsushi Yonechi, Mika Hoshino, Jun Osugi, Yutaka Shio, Mitsunori Higuchi, Junji Ezaki, Satoshi Waguri, Mitsukazu Gotoh, Hiroyuki Suzuki
Journal: Cancer Research (2016)

Abstract Background: We have reported the usefulness of Family with sequence similarity 83, member B (FAM83B) as a novel biomarker for diagnosis and prognosis of lung squamous cell carcinoma. FAM83B expresses not only in lung cancer but also in several types of solid cancer such as breast, esophageal, and so on. More recently, novel finding showing FAM83B involve to the resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in breast cancer cell lines has been shown. EGFR signaling pathway also plays an important role in lung adenocarcinoma, therefore we hypothesize that FAM83B associates to the tumor proliferation in lung adenocarcinoma, and its results in the resistance to EGFR TKI and in a novel therapeutic target in lung adenocarcinoma. Materials and methods: Sixty-four paired tumor and corresponding normal tissue samples obtained from patients with lung adenocarcinoma who underwent surgical resection since 2008 to 2011 were subjected. FAM83B mRNA expression were examined and analyzed relationship between the level of FAM83B and clinicopathological variables. Then, FAM83B knock down study was performed in several types of cancer cell lines (PC-14, H820, H1650, H1975, HLC-1, H2347) to understand whether FAM83B involve to cell proliferation. Results: Multivariate analysis show that smaller cancer(≦3cm vs &amp;gt;3cm, p = 0.044), and wild type EGFR(wild type vs. mutant, p = 0.004) tend to express higher FAM83B mRNA. There is no significant difference between FAM83B expression and progression-free survival. FAM83B knock down results in suppression of proliferation in HLC-1, H1650, which express high level of FAM83B protein. Conclusions: FAM83B could involve to tumor proliferation of lung adenocarcinoma in part, and could be the novel therapeutic target. Citation Format: Takumi Yamaura, Naoyuki Okabe, Hironori Takagi, Yuki Owada, Takuya Inoue, Yuzuru Watanabe, Mitsuro Fukuhara, Satoshi Muto, Yuki Matsumura, Takeo Hasegawa, Atsushi Yonechi, Mika Hoshino, Jun Osugi, Yutaka Shio, Mitsunori Higuchi, Junji Ezaki, Satoshi Waguri, Mitsukazu Gotoh, Hiroyuki Suzuki. Functional analysis of family with sequence similarity 83, member B in lung adenocarcinoma. [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 422.
Abstract 4142: Proteomics analysis of breast cancer cell-specific proteins that are transferred to immune cells via trogocytosis
Authors: Eiji Suzuki, Masashi Inoue, Shinji Ito, Junko Satoh, Kosuke Kawaguchi, Ayane Yamaguchi, Moe Tsuda, Masakazu Toi
Journal: Cancer Research (2016)

Abstract We previously reported that HER2 is transferred from HER2 overexpressing breast cancer cells to CD14+ monocytes via trastuzumab dependent trogocytosis (Suzuki et al. BMC cancer 2015) and EGFR of MDA-MB-231 (triple negative human breast cancer cell line) is also transferred to immune cells via trogocytosis and those immune cells express EGFR on the cell surface without therapeutic antibody administration (AACR 2015 #2349). There are several reports that suggest that trogocytosis might act to stimulate immunological tolerance or immune effector cell activation, however its immunological roles still remain unclear. Therefore, in order to clarify the role of trogocytosis, we study the profile of proteins that potentially are transferred from cancer cell to immune cell via trogocytosis. Human triple negative breast cancer cell line, MDA-MB-231 that was cultured with the medium containing arginine labeled with 13C instead of normal 12C (SILAC method, ThermoFisher Scientific) was co-cultured with human peripheral blood mononuclear cell (PBMC) that was cultured with normal medium. The cell mixture was labeled with CD45+ magnetic beads and CD45+ cell (PBMC) and CD45- cell (MDA-MB-231) were separated by MACS cell separation kit (Miltenyi Biotec). Proteins of PBMC that were passed the trogocytosis were resolved on SDS-PAGE and LC-MS/MS was carried out to identify the cancer specific trogocytosed proteins in PBMC by SILAC method. We found that proteins with higher H/L ratio were included in many of cytoskeletal proteins and interestingly mitochondrial metabolism related proteins of cancer cells were also detected in PBMC. Those up-regulated proteins in PBMC were reduced in MDA-MB-231. The findings suggested that the role of trogocytosis of PBMC on breast cancer cell might be involved in metabolisms of both cancer cell and immune cell. Thus, we are exploring the effect of trogocytosis on cancer cell metabolisms especially on mitochondrial related metabolism that could be reduced by immune cell trogocytosis and also on metabolism of immune cells themselves that capture the cancer cell proteins via trogocytosis. Citation Format: Eiji Suzuki, Masashi Inoue, Shinji Ito, Junko Satoh, Kosuke Kawaguchi, Ayane Yamaguchi, Moe Tsuda, Masakazu Toi. Proteomics analysis of breast cancer cell-specific proteins that are transferred to immune cells via trogocytosis. [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 4142.
Feasibility and acceptability of patient-reported outcomes data collection for clinical care following breast reconstruction.
Authors: Andrea Pusic, Anne Klassen, Amie Scott, Stefan Cano, Marwan Shouery, Ethan M. Basch
Journal: Journal of Clinical Oncology (2012)

9042 Background: To date, systematic measurement of patient-reported outcomes (PROs) has played an important role in cancer research, but not in routine clinical care. Our objective was to evaluate the feasibility of developing and piloting an electronic PRO data collection in clinical care among breast reconstruction patients using the BREAST-Q, a previously developed condition-specific PRO measure for breast surgery patients that measures quality of life (e.g. psychosocial, physical and sexual well-being) as well as patient satisfaction (e.g. satisfaction with breasts, with information, with surgeon). Methods: The BREAST-Q was loaded to the MSKCC WebCore, a generic electronic patient-reporting platform adhering to strict privacy and security standards. Patients attending visits at the MSKCC Breast Reconstruction Clinic were asked to complete the BREAST-Q electronically prior to scheduled visits. For patients with email addresses, a reminder with web-link to the questionnaire was emailed automatically prior to the visit. Results: Over a 9 month start-up period, BREAST-Q surveys were completed by 1442 patients. Patients completed the questionnaire at set time points before and after surgery. A total of 2340 BREAST-Q surveys were completed overall. Mean completion time was 5:53 minutes. Acceptability was high with both patients and clinical staff contributing positive comments along with suggestions for improvement via email. Conclusions: This pilot experience suggests that ePRO data can be efficiently collected among outpatient breast surgery patients with high acceptability. In the next phase of this project, we will introduce real-time individual patient reports to the clinical team and evaluate the impact of this information on clinical care and quality improvement.
Dozens of Turkish doctors are among those detained after coup
Authors: Owen Dyer
Journal: BMJ (2016)

Beatings, torture, and abuse have been commonplace in police stations and temporary detention centres holding over 10 000 people detained in the aftermath of Turkey’s failed coup, eyewitnesses have told Amnesty International.

At least one hospital in Turkey and one in Somalia have been closed, as officials said they were linked to the Fethullah Terrorist Organisation, the government’s name for the network of institutions associated with Pennsylvania based Islamic preacher Fethullah Gulen, whom Turkey accuses of orchestrating the failed coup.

More than 45 000 public employees have been dismissed and at least 13 165 people detained to date. Arrests, sackings, and institutional closures are likely to continue for weeks as multiple investigations target alleged Gulenist infiltration of public institutions. The detained include 8838 soldiers, 2101 judges and prosecutors, 1485 police officers, and 689 civilians.

Many detainees are being held in …
Hollow victories and hepatitis C
Authors: Navjoyt Ladher
Journal: BMJ (2016)

Hollow victories and hepatitis CNavjoyt Ladher analysis editor, The BMJ When Gilead Sciences introduced sofosbuvir based antivirals in 2014, the drugs were touted as a breakthrough for people with hepatitis C infection, promising high cure rates and fewer complications such as cirrhosis and hepatocellular carcinoma.But with astronomical prices challenging healthcare budgets and limiting access to these drugs, this promise remains out of reach for many patients.
Abstract 4370: Genome-wide CRISPR-Cas9 screens reveal loss of redundancy between PKMYT1 and WEE1 in patient-derived glioblastoma stem-like cells
Authors: Chad Toledo, Ding Yu, Pia Hoellerbauer, Ryan Davis, Ryan Basom, Emily Girard, Philip Corrin, Hamid Bolouri, Jerry Davison, Qing Zhang, Do-Hyun Nam, Jeongwu Lee, Steven Pollard, Jeffery Delrow, Bruce Clurman, James Olson, Patrick Paddison
Journal: Cancer Research (2016)

Abstract Glioblastoma multiforme (GBM) is the most aggressive and common form of brain cancer in adults. There are currently no effective therapies for GBM. Even with standard of care treatments, such as surgery, radiation, and chemotherapy, ∼90% of adult patients die within 2 years of diagnosis. To identify therapeutic targets for Glioblastoma (GBM), we performed genome-wide CRISPR-Cas9 “knockout” (KO) screens in patient-derived GBM stem-like cells (GSCs) and human neural stem/progenitors (NSCs), non-neoplastic stem cell controls, for genes required for their in vitro growth. Surprisingly, the vast majority GSC-lethal hits were found outside of molecular networks commonly altered in GBM and GSCs (e.g., oncogenic drivers). In vitro and in vivo validation of GSC-specific targets revealed several strong hits, including the wee1-like kinase, PKMYT1/Myt1. Mechanistic studies demonstrated that PKMYT1 acts redundantly with WEE1 to inhibit Cyclin B-CDK1 activity via CDK1-Y15 phosphorylation and to promote timely completion of mitosis in NSCs. However, in GSCs, this redundancy is lost, likely as a result of oncogenic signaling, causing GBM-specific lethality. From a biological standpoint, our results help re-discover PKMYT1 function in human cells. From a cancer standpoint, these results suggest that targeting PKMYT1 is a glioma-lethal gene and that tandem or sequential use of PKMYT1 and WEE1 inhibitors may illicit therapeutic responses in GBM. In addition to these results we will also present retest data for other candidate glioma-lethal genes and networks in multiple patient samples. Citation Format: Chad Toledo, Ding Yu, Pia Hoellerbauer, Ryan Davis, Ryan Basom, Emily Girard, Philip Corrin, Hamid Bolouri, Jerry Davison, Qing Zhang, Do-Hyun Nam, Jeongwu Lee, Steven Pollard, Jeffery Delrow, Bruce Clurman, James Olson, Patrick Paddison. Genome-wide CRISPR-Cas9 screens reveal loss of redundancy between PKMYT1 and WEE1 in patient-derived glioblastoma stem-like 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 4370.
Induction of Cirrhosis of the Liver and of Hepatomas in Mice With Carbon Tetrachloride
Authors: Jesse E. Edwards, Albert J. Dalton
Journal: JNCI Journal of the National Cancer Institute (1942)

Journal Article Induction of Cirrhosis of the Liver and of Hepatomas in Mice With Carbon Tetrachloride Get access Jesse E. Edwards, Jesse E. Edwards research fellow Search for other works by this author on: Oxford Academic PubMed Google Scholar Albert J. Dalton Albert J. Dalton cytologist 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 19–41, https://doi.org/10.1093/jnci/3.1.19 Published: 01 August 1942
The impact of 5HT3RA antiemetics on the incidence of chemotherapy-induced nausea and vomiting (CINV), treatment adherence, and delay of therapy in early-stage breast cancer (BC) patients treated with moderately/highly emetogenic chemotherapy (MEC/HEC).
Authors: Hope S. Rugo, Swetha Palli, Michael Grabner, Ralph A. Quimbo, Russell L. Knoth
Journal: Journal of Clinical Oncology (2012)

75 Background: The effectiveness of 5-HT 3 receptor antagonists (5HTs) for the prevention of CINV is well established. Less is known about the impact of these drugs on chemotherapy adherence (AD) and preventing delayed therapy (DT). We examined the impact of palonosetron (PAL) vs. other 5HTs on CINV incidence, treatment AD and DT in early-stage BC. Methods: An observational nested case-control study was conducted using the HealthCore Integrated Research Database (HIRD). Female patients (pts) were identified by their first claim for IV MEC/HEC between 1/1/02 and 10/31/10 (index). Inclusion criteria were: ≥ 12 months health plan eligibility pre-index (baseline) and ≥ 6 months post-index (follow-up); ≥ 1 baseline claim for BC; no claim for secondary or multiple primary neoplasms; and ≥ 1 claim for 5HT during follow-up. CINV was defined using ICD-9 codes for nausea, vomiting, or related events, and use of rescue medications for 5 days after MEC/HEC. AD was defined as receiving the requisite number of cycles within the recommended NCCN timeframe. DT was defined as exceeding 2x the NCCN-recommended cycle length between MEC/HEC claims. Outcomes were assessed using descriptive analysis and multivariate logistic regression, controlling for demographics, baseline medical conditions, and index therapy. Results: We identified 682/696 [MEC] and 1,782/3,103 [HEC] pts who received PAL or other 5HTs, respectively. For PAL vs. 5HT, 33.7% vs. 49.7% (OR: 0.51; 95% CI 0.41-0.65; p&lt;0.01) had CINV (mean 0.27 vs. 0.61 events/cycle) in the MEC group; in the HEC group, 27.3% vs. 35.7% (OR: 0.61; 95% CI 0.53-0.7; p&lt;0.01) had CINV (mean 0.21 vs. 0.34 events/cycle). PAL users delayed MEC at a lower rate than those using other 5HTs (2.6% vs. 8.2%; OR: 0.37; CI 0.21-0.65; p&lt;0.01) but had similar AD (41.8% vs. 37.2%; OR: 1.2; CI 0.95-1.5; p=0.12). No differences in AD or DT were found among pts on HEC. Conclusions: Among early-stage BC pts initiating a MEC or HEC agent, PAL was associated with fewer CINV events, a lower (MEC) or equal (HEC) rate of delayed therapy, and equal adherence compared to other 5HTs.
Abstract 2721: Discovery and development of orally available subnanomolar potent checkpoint kinase 1 inhibitors as potential anticancer therapies
Authors: Alex C. Vo, Janelle Taylor, Robert Rosler, Dina Leviten, Teresa Sierra, Richard Boyce, Robert Boyle, Scott Peterson, Kevin Klucher
Journal: Cancer Research (2016)

Abstract Checkpoint kinase 1 (Chk1) is a serine/threonine protein kinase that regulates cell division by arresting progression in the S &amp; G2 phases of the cell cycle in response to genotoxic stress. Pharmacological inhibition of Chk1 selectively uncouples the completion of DNA replication from G2/M phase transition in tumor cells lacking parallel cell cycle checkpoint controls, resulting in mitotic catastrophe and cell death. These properties make Chk1 inhibition a unique therapeutic approach as a single agent or as a means to enhance the efficacy of DNA-targeted chemotherapeutic drugs. In this report, we describe our progress in the development of orally bioavailable, potent and selective Chk1 inhibitors derived from an aminopyrazole chemical scaffold. Starting with the lead compound, ONT-2409 (IC50 of &amp;lt;0.1 nM against the Chk1 enzyme), a series of Chk1 inhibitors have been developed. Lead candidates have been generated with potent biochemical IC50s against Chk1 (IC50s = 0.1-0.3 nM). In a panel of 125 protein kinases the top candidates were shown to be highly selective for Chk1, with little appreciable activity against Chk2 or other kinases involved in cell cycle control/DNA damage response. The lead candidates have potent single agent activity against a panel of diverse cancer cell lines (EC50s = 0.03-0.4 μM) and show synergistic enhancement in the activity of clinically relevant DNA targeted chemotherapeutics. Mechanistically, the lead candidates abrogate gemcitabine-induced cell cycle arrest and induce apoptotic cell death. Biomarker studies show the lead candidates inhibit gemcitabine-induced auto-phosphorylation of Chk1 at S296 and reduce phosphorylation of CDK1 at Y15. Compared with ONT-2409, the optimized candidates display improved cell permeability/efflux ratios, superior intrinsic microsomal and hepatic half-lives, and have excellent oral bioavailability in mice and rats. Lead candidate Chk1 inhibitors have also demonstrated potent potentiation of DNA targeted chemotherapies and single agent activity in xenograft tumor models Citation Format: Alex C. Vo, Janelle Taylor, Robert Rosler, Dina Leviten, Teresa Sierra, Richard Boyce, Robert Boyle, Scott Peterson, Kevin Klucher. Discovery and development of orally available subnanomolar potent checkpoint kinase 1 inhibitors as potential anticancer therapies. [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 2721.
Lack of Protein Kinase C Alpha Is Associated with Poor Prognosis in Pediatric T-Lineage Acute Lymphoblastic Leukemia
Authors: Gloria Milani, Benedetta Accordi, Marco Giordan, Silvia Bresolin, Luisa Galla, Manuela Sciro, Elena Vendramini, Giovanni Cazzaniga, Geertruy Kronnie, Giuseppe Basso
Journal: Blood (2011)
Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer: a retrospective, pooled biomarker study
Authors: Enric Domingo, Luke Freeman-Mills, Emily Rayner, Mark Glaire, Sarah Briggs, Louis Vermeulen, Evelyn Fessler, Jan Paul Medema, Arnoud Boot, Hans Morreau, Tom van Wezel, Gerrit-Jan Liefers, Ragnhild A Lothe, Stine A Danielsen, Anita Sveen, Arild Nesbakken, Inti Zlobec, Alessandro Lugli, Viktor H Koelzer, Martin D Berger, Sergi Castellví-Bel, Jenifer Muñoz, Marco de Bruyn, Hans W Nijman, Marco Novelli, Kay Lawson, Dahmane Oukrif, Eleni Frangou, Peter Dutton, Sabine Tejpar, Mauro Delorenzi, Rachel Kerr, David Kerr, Ian Tomlinson, David N Church
Journal: The Lancet. Gastroenterology & hepatology (2016)
P0907 : Pharmacokinetics, pharmacodynamics, and toxicity profile of RG-101, a novel GalNAc-conjugated hepatocyte-targetng inhibitor of microrna-122, in rodents and cynomolgus monkeys
Authors: S. Neben, K. Liu, C. Berman, J. Tay, C. Esau, R. Kaiser, B. Wahle, N. Chau, B. Bhat, N.W. Gibson
Journal: Journal of Hepatology (2015)
Trisomy 21-Associated Abnormalities in IGF Signalling and the Fetal Microenvironment Both Contribute to Disruption of Fetal Hematopoiesis in Down Syndrome
Authors: David O'Connor, Binbin Liu, Gillian Cowan, Anindita Roy, Katerina Goudevenou, Neha Bhatnagar, Oliver Tunstall, Josu de la Fuente, Anastasios Karadimitris, Irene Roberts
Journal: Blood (2014)
Abstract 1676: 15-Lipoxygenase-2 inhibits epithelial-to-mesenchymal transition (EMT) in metastatic prostate cancer
Authors: Rana K. Alfardan, Debasish Boral, Daotai Nie
Journal: Cancer Research (2016)

Abstract Introduction 15-lipoxygenase-2 (15-LOX-2) is a lipid oxidizing enzyme which converts the unsaturated fatty acids (Arachidonic and linoleic acid) to bioactive lipids with anti-inflammatory properties. Abundantly expressed in normal prostate, 15-LOX-2 expression and activities were found reduced in prostate tumors. 15-LOX-2 has been suggested as functional tumor suppressor since restoration of its expression was found to reduce prostate tumor formation and growth and induce tumor dormancy. However, it is unknown how 15-LOX-2 modulates prostate tumor progression and metastasis. Methods Silico analyses of gene array data, Inducible Tet-on system to express 15-LOX-2 in PC3MM cells in an inducible manner, qPCR to check the expressions, western blot, wound healing assay, immunohistochemistry. Result Through in silico analyses of gene array data, we found 15-LOX-2 expression was markedly reduced in metastatic prostate tumors when compared to normal or primary prostate tumor tissues. To determine whether 15-LOX-2 can modulate metastatic potentials of prostate cancer, we used an Inducible Tet-on system to express 15-LOX-2 in PC3MM cells. Treatment with 750ng/ml of doxycycline led to induced expression of 15-LOX-2 in PC3MM cells. Restoration of 15-LOX-2 expression in PC3MM cells caused re-expression of several epithelial markers including claudin, desmocollin, desmoglein, Jam, EPCAM, β-Catenin molecules involved in the tight and desmosomal junctions. At mean time, 15-LOX-2 expression led to a decrease in the levels of mesenchymal markers, vitronectin and fibronectin, in PC3MM cells. Restoration of 15-LOX-2 expression in PC3MM cells reduced cell migration and reduced MMP2 and MMP3 expression. Conclusion Our data suggest that 15-LOX-2 is a barrier for prostate tumor cells to acquire metastatic potentials through inhibiting epithelial to mesenchymal transition. Citation Format: Rana K. Alfardan, Debasish Boral, Daotai Nie. 15-Lipoxygenase-2 inhibits epithelial-to-mesenchymal transition (EMT) in metastatic 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 1676.
Prognostic Impact of MUM1/IRF4 Expression in Burkitt Lymphoma (BL): A Reappraisal of 89 BL Patients in Japan
Authors: Akira Satou, Naoko Asano, Seiichi Kato, Ahmed Ali Elsayed, Naoya Nakamura, Koichi Ohshima, Shigeo Nakamura
Journal: Blood (2015)