tbuckley/cabot-search huggingface dataset:
Abstract 2167: Strengthening anti-cancer effects on non-small cell lung carcinoma by dual blockage of MET and EGFR in a context-dependent manner.
Authors: Yu-Wen Zhang, Ben Staal, Curt Essenburg, Steven Lewis, Dafna Kaufman, George F. Vande Woude
Journal: Cancer Research (2013)

Abstract Non-small cell lung carcinoma (NSCLC) accounts for more than 80% of lung cancer, the leading cause of death among all cancer casualties. The MET receptor tyrosine kinase (RTK) is often co-expressed with EGFR in the NSCLC cells, and is an important alternative resistant mechanism for escaping EGFR-targeted therapy. To assess the benefit of dual blockage of MET and EGFR for NSCLC therapy, we investigated the activities of these two RTK pathways in several NSCLC cell lines carrying distinct cellular contexts, and determined their responses to SGX523 and erlotinib, the small molecule kinase inhibitors of MET and EGFR, respectively. Here, we showed that MET can cross-activate EGFR in MET-amplified or overexpressing cells via hetero-receptor dimerization, and the MET-dependent phosphorylation of EGFR can be abolished by SGX523 but not by erlotinib. More importantly, combined inhibition of MET and EGFR in vitro results in a maximal suppression of downstream ERK and AKT activation and of cell proliferation when their ligands (HGF and EGF) are present. Furthermore, we demonstrated that SGX523 and erlotinib combination strengthens anti-cancer activity in vivo in a cellular context-dependent manner. The combination led to regression of MET-amplified H1993 tumors by enhancing suppression of proliferation and inducing apoptosis, whereas significantly reduced MET-non-amplified H1373 tumor growths by suppression of proliferation without inducing apoptosis. Although SGX523 alone was sufficient to achieve near complete regression of MET-addicted EBC-1 tumors, its combination with erlotinib strongly inhibited viability of a population of SGX523-insensitive cells emerging from SGX523-treated EBC-1 tumor relapse. Our data suggest that dual blockage of MET and EGFR can enhance anti-cancer effects on NSCLC in a context-dependent manner, and provide a strong rationale and mechanisms for combining MET and EGFR inhibitors for NSCLC therapy. Citation Format: Yu-Wen Zhang, Ben Staal, Curt Essenburg, Steven Lewis, Dafna Kaufman, George F. Vande Woude. Strengthening anti-cancer effects on non-small cell lung carcinoma by dual blockage of MET and EGFR in a context-dependent manner. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2167. doi:10.1158/1538-7445.AM2013-2167
Abstract 278: Role of AF4 and Dot1 in MLL-AF9 mediated leukemogenesis
Authors: Bhavna Lumba, Charles S. Hemenway
Journal: Cancer Research (2011)

Abstract Mixed lineage leukemia (MLL) is characterized by rearrangement of the MLL gene at chromosome band 11q23. MLL gene rearrangements give rise to chimeric proteins that contain the N-terminal portion of MLL fused to the C-terminal portion of over 50 different fusion partners. MLL chimeras do not retain the histone methyltransferase activity of wild type MLL and it is unclear how they deregulate the expression of MLL target genes. Our laboratory studies the two most common MLL fusion partners encountered in patients with leukemia, AF4 and AF9. We have previously shown that AF4 and AF9 heterodimerize and peptides that block this interaction are toxic to MLL leukemia cell lines. This supports the hypothesis that the interaction of MLL-AF9 with AF4 is required for leukemogenesis. However, we have also shown that AF4 and H3K79 methyltransferase, Dot1 have similar binding sites on AF9. Furthermore, we have found that Dot1 is required for immortalization of hematopoietic progenitor cells by MLL fusion genes. The work of Yokoyama and others demonstrated that AF4, ENL (a close homologue of AF9) and Dot1L do not exist in the same multimeric complex. To understand the role of AF4 and Dot1 in MLL-AF9 mediated leukemogenesis, we made point mutants of AF9 with differential binding for AF4 and Dot1. Based on our preliminary data and recent studies, we hypothesize that the binding of AF4 and not Dot1 to MLL-AF9 is required for MLL-AF9 mediated leukemogenesis. Nevertheless, Dot1 remains a critical factor in MLL-AF9 leukemia. We hypothesize that Dot1 recruitment is mediated by wild type AF9 rather than MLL-AF9. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 278. doi:10.1158/1538-7445.AM2011-278
630 HIGH SERUM LEVELS OF THE INTERLEUKIN 33 RECEPTOR SOLUBLE ST2 AS A NEGATIVE PROGNOSTIC FACTOR IN HEPATOCELLULAR CARCINOMA
Authors: D. Bergis, V. Kassis, A. Ranglack, V. Koeberle, A. Piiper, B. Kronenberger, S. Zeuzem, O. Waidmann, H.H. Radeke
Journal: Journal of Hepatology (2013)
Abstract 678: Study of 2, 9-disecbutyl-1, 10-phenanthroline as a novel anticancer agent
Authors: Dongsheng Wang, A.R.M. Ruhul Amin, Shifang Peng, Chinar Sanghvi, Dong M. Shin, Jack F. Eichler
Journal: Cancer Research (2011)

Abstract Development of new, safe, and effective drugs or strategies targeting molecular events and pathways which are responsible for cancer initiation and progression is an urgent need to improve cancer patient care. In this study, we tested the antitumor effect of a novel agent, 2, 9-disecbutyl-1, 10-phenanthroline (dsBPT), a 1, 10-phenanthroline derivative. Both in vitro cell line and in vivo xenograft models were applied to study the antitumor efficacy and underlying mechanism of this compound. IC50s were initially determined using lung cancer cell lines: A549 (0.25 μM) and H1703 (0.1 μM), head and neck cancer cell lines: TU686 (0.08 μM) and TU212 (0.2 μM), and normal bronchial epithelial cells: BEAS-2B (2.0 μM), indicating that the growth inhibitory effect of dsBPT on cancer cell lines was about 10 times greater than that on normal human epithelial cells. Further studies demonstrated that dsBPT at a concentration of 1-2 μM induced autophagy and G1 cell cycle arrest. At higher doses between 4-8 μM, the compound further induced apoptosis (40-80%). Combination of dsBPT with the cytotoxic agent cisplatin synergistically inhibited cancer cell growth (combination index = 0.3) and induced apoptosis (80-90%) at a concentration of 1 μM for each drug. Two experiments were then performed to test dsBPT in vivo. First, xenografted mice implanted with TU212 cells were treated with three drug doses (2mg/kg, 5mg/kg, 10mg/kg). Compound was given by IV injection once per week for 3 weeks. We found that 10 mg/kg treatment significantly reduced tumor growth as compared with the control group (p = 0.004). Under the same treatment schedule, further study showed that the combination of dsBPT (2 mg/kg) with cisplatin (2 mg/kg) significantly reduced the tumor volume as compared with the untreated control (p = 0.0017), while each of the single drugs at the same concentration showed no significant inhibitory effect on tumor growth (p = 0.10 and 0.15 for cisplatin and dsBPT, respectively). Neither significant weight loss nor major organ damage was observed by histology examination in the experimental animals in this study. In summary, our study suggests that dsBPT is a novel, highly potent antitumor drug that warrants further preclinical and clinical development either as a single agent or in combination with known chemotherapy drugs such as cisplatin. (This study is supported by grants from DOD W81XWH-07-1-0306 Project 5, and GCC Distinguished Scholar Award to ZC). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 678. doi:10.1158/1538-7445.AM2011-678
Values of endoscopic ultrasonography for diagnosis and treatment of duodenal cysts
Authors: Guo-Qiang Xu, Wei-Hua Yu, Xiao-Dong Teng, Feng-Ling Wu, Qing Gu, Xiao-Qi Zhong, Li-Ying Gu, Cai-Qing Qian
Journal: Endoscopy (2011)

Objective: Duodenal cysts is one of submucosal protruding lesions, it is a cystic change in intraintestinal wall. In the past, it was thought as a rare disease, not introduced and described in textbooks in detail. But recently, the disease is more and more found and acknowledged with the development of endoscopic equipment and technique. It is an important issue for clinicans to diagnose correctly and treat reasonably this disease. endoscopic ultrasonograhy (EUS)has the functions both endoscopy and ultrasonography, which can show the structure of the intestinal wall and the relationship with the adjacent organs. The clinical application of EUS has greatly improved the our diagnosis, treatment and understanding levels of this kind of diseases.
Tc-99m MDP and Tc-99m MIBI Dual Imaging of Photopenic Bone Metastases of Carcinoma of the Larynx
Authors: FATMA BERK, HAKAN DEMIR, OKAN ERDINCLER, SERKAN ISGÖREN, CUMALI AKTOLUN
Journal: Clinical Nuclear Medicine (2002)

BERK, FATMA M.D., M.Sc.; DEMIR, HAKAN M.D.; ERDINCLER, OKAN M.D.; ISGÖREN, SERKAN M.D.; AKTOLUN, CUMALI M.D., M.Sc. Author Information
OP0030 Osteoarthritis and Bone Mineral Density of the Hand
Authors: R. Ramonda, E. Musacchio, P. Frallonardo, M. Lorenzin, L. Sartori, L. Punzi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Among the main subsets of osteoarthritis of the hand (HOA): there are nodal OA (NOA) and erosive (EHOA). Although this last form affects most frequently middle-aged women only few data are still available on bone mineral density (BMD) of these patients. <h3>Objectives</h3> To study the prevalence of low BMD in patients with EHOA and NOA, who consecutively underwent phalangeal radiographic absorptiometry (pRA) in our outpatient clinic, compared to matched healthy subjects. <h3>Methods</h3> Two cohorts of subjects for a total of 76 patients fulfilling ACR criteria for hand OA were studied. Patients showing at least one erosion in interphalangeal (IP) joints were included in the EHOA group, while patients with erosions in the metacarpophalangeal joints were excluded. Patients were also evaluated for disease duration, number of affected active (swollen and painful or tender) joints (NAAC), radiographic in Kellgren &amp; Lawrence score (RS), Body Mass Index (BMI) (kg/m2) was also calculated (Table 1). All the patients and 190 healthy subjects (N) (mean age 67.8±7.7 years) underwent pRA scanning at the 2nd, 3rd and 4th finger of the non-dominant hand by means of a monoenergetic X rays (60 kV) equipment (Alara Metriscan, Hayward, Ca, USA). BMD was estimated in the three middle phalanges and the average expressed as mineral mass/area (g/cm2). T and Z scores were also provided by the instrument using local reference data. The local Ethics Committee granted approval of the study protocol and all patients gave their informed consent. <h3>Results</h3> A reduction of BMD fitting osteopenia was found in 35% of patients with EHOA, 21% with NOA, and 43% of N (p=0.03, EHOA <i>vs</i> NOA), while osteoporosis affected 20% with EHOA, 28% with NOA, and 20% N. BMD was higher in EHOA with respect to both the NOA and N groups (p=0.025 and p&lt;0.05, respectively). T and Z scores were significantly higher in the EHOA vs the N population (T: p=0.01; Z: p&lt;0.01). There were no statistically significant differences between NOA and healthy subjects. <h3>Image/graph</h3> <h3>Conclusions</h3> Phalangeal BMD was higher in EHOA patients with respect to both N and NOA subjects. Joint erosion and inflammation do not appear to determine sufficient phalangeal bone loss to discriminate EHOA vs NOA. To a certain extent, higher mineral density could be explained by more pronounced osteoreparative processes in EHOA than in NOA. This issue needs further investigation to better understand the relationship between osteoarthritis and local osteoporosis and the possible interferences with instrumental evaluation. <h3>Disclosure of Interest</h3> None Declared
Integration of health and social care needs financial incentives, experts say
Authors: N. Hawkes
Journal: BMJ (2012)

After years of talk, is integrated care about to become a reality in England? Three politicians from the leading political parties offered a mixed message at a meeting at the healthcare think tank the King’s Fund on 1 May.

As befitted the parties, the Conservative and Liberal Democrat representatives, Sarah Wollaston and Judith Jolly, were cautiously positive that the new Health and Social Care Act might advance the cause. But Norman Warner for Labour, a health minister in the previous government, identified a host of familiar obstacles.

Local activists, who had been given a leading role by the act, would never have reformed the NHS by themselves, said Warner. Direction from the centre was always necessary. And although a few examples of integrated care could be discerned—Torbay, Herefordshire, and Southwark …
Abstract 4482: Pemetrexed treatment results in DNA replication fork instability and double strand breaks formation in UNG-/- human cancer cells.
Authors: Lachelle D. Weeks, Gabriel Zentner, Peter Scacheri, Stanton L. Gerson
Journal: Cancer Research (2013)

Abstract Misincorporation of genomic uracil and formation of DNA double strand breaks are known consequences of exposure to TS inhibitors such as 5-fluorouracil, and pemetrexed. Uracil DNA glycosylase catalyzes the excision of genomic uracil and initiates DNA base excision repair (BER). Thus, a relationship between antifolate cytotoxicity and UNG expression and activity has been hypothesized. However, a precise mechanism linking antifolate-induced formation of DSBs to genomic uracil accumulation and UNG-initiated BER has not been described. Herein, we report that despite equivalent proliferation indices, DLD1 UNG-/- cells are more sensitive to pemetrexed mediated intra S-phase arrest, DNA double strand break formation and apoptosis compared to UNG+/+ cells. Using data from western blots in chromatin extracts, PCNA staining of cells in S-phase, and pulse-chase labeling of replicating cells with CldU and IdU, we surmise that the accumulation of uracil in pemetrexed-treated UNG-/- cells is associated with significant replication fork instability. In addition, UNG-/- cells have reduced capacity to recover from pemetrexed-mediated DNA damage, as indicated by the persistence of S-phase arrest and gamma-H2AX foci. This defect in recovery was not explained by double strand break repair capacity, which was equivalent in UNG+/+ and UNG-/- cells. Using γ-H2AX ChIP sequencing, we observed a 5-fold increase in the number of γ-H2AX binding sites in UNG-/- cells compared to UNG+/+ cells treated at IC50 levels of pemetrexed. This analysis evinced distinct patterns of γ-H2AX binding in UNG+/+ and UNG-/- cells. Double strand breaks (γ-H2AX) were more significantly associated with transcription start sites and putative origins of replication in UNG-/- cells compared to UNG+/+ cells. Based on these data we conclude that uracil accumulation, and thus UNG activity, during pemetrexed exposure directs both the quantity and the location of double strand breaks. These findings support uracil mediated S-phase arrest and DNA replication fork collapse as the mechanism of double strand break formation and cell death in pemetrexed treated UNG-/- cells. Citation Format: Lachelle D. Weeks, Gabriel Zentner, Peter Scacheri, Stanton L. Gerson. Pemetrexed treatment results in DNA replication fork instability and double strand breaks formation in UNG-/- human cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4482. doi:10.1158/1538-7445.AM2013-4482
Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer
Authors: Susan J. Ramus, Honglin Song, Ed Dicks, Jonathan P. Tyrer, Adam N. Rosenthal, Maria P. Intermaggio, Lindsay Fraser, Aleksandra Gentry-Maharaj, Jane Hayward, Susan Philpott, Christopher Anderson, Christopher K. Edlund, David Conti, Patricia Harrington, Daniel Barrowdale, David D. Bowtell, Kathryn Alsop, Gillian Mitchell, Mine S. Cicek, Julie M. Cunningham, Brooke L. Fridley, Jennifer Alsop, Mercedes Jimenez-Linan, Samantha Poblete, Shashi Lele, Lara Sucheston-Campbell, Kirsten B. Moysich, Weiva Sieh, Valerie McGuire, Jenny Lester, Natalia Bogdanova, Matthias Dürst, Peter Hillemanns, Kunle Odunsi, Alice S. Whittemore, Beth Y Karlan, Thilo Dörk, Ellen L. Goode, Usha Menon, Ian J. Jacobs, Antonis C. Antoniou, Paul D. P. Pharoah, Simon A. Gayther
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, responsible for 13 000 deaths per year in the United States. Risk prediction based on identifying germline mutations in ovarian cancer susceptibility genes could have a clinically significant impact on reducing disease mortality.
Abstract P4-03-11: SUVmax of FDG-PET/CT is Associated with Chemotherapy Response Assay Test Results and Prognostic Factors in Breast Cancer Patients
Authors: A Lee, J Chang, B Bang, J Lee, D Han, S Min, C Yun, BS Kim, W Lim, N Paik, B-I Moon
Journal: Cancer Research (2012)

Abstract Backgrounds:18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) is widely used for cancer evaluation and there are several studies which suggested maximum standard uptake value (SUVmax) may reflect the cancer patients' prognosis. Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) is commonly used as a chemosensitivity assay modality for the treatment of various cancers in clinical settings and there have been several studies on its usefulness in breast cancer. We previously reported chemosensitivity (ATP-CRA) results might reflect patients' prognosis. So we supposed that SUVmax could reflect chemosenitivity (ATP-CRA) results of patients, so performed this study to analyze the relationship between PET/CT SUVmax and chemosenstivity (ATP-CRA) results of these drugs. Furthermore, we evaluated prognostic factors for breast cancer according to SUVmax. Materials and Methods: 102 breast cancer patients, who underwent PET/CT and chemosensitive (ATP-CRA) test between December 2010 and April 2012, were enrolled in this study. We analyzed, retrospectively, the correlation between SUVmax of PET/CT and chemosenitivity (ATP-CRA) results of doxorubicin/paclitaxel. SUVmax according to prognostic factors were also assessed. Results: Chemosensitivity (ATP-CRA) results of doxorubicin and paclitaxel have significant positive correlation with SUVmax. Their correlation coefficient were 0.236 (p = 0.020) and 0.216 (p = 0.030), respectively. Patients with larger tumor size, higher histologic and nuclear grade, estrogen receptor negative, progesterone receptor negative, HER2 positive, and Ki67 positive (≥14%) have higher mean SUVmax values (p &amp;lt; 0.05). In molecular subgroup analysis, triple negative group showed higher mean SUVmax values than luminal A group (p &amp;lt; 0.001). Conclusion: Higher SUVmax values of PET/CT is correlated with better chemosensitive (ATP-CRA) results of doxorubicin and paclitaxel, and poor prognostic factors of breast cancer. However, examination of additional cases might be needed. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-03-11.
P1114 PATIENT-REPORTED OUTCOMES (PROS) IN CHRONIC HEPATITIS C PATIENTS WITH CIRRHOSIS TREATED WITH SOFOSBUVIR (SOF) CONTAINING REGIMENS
Authors: Z.M. Younossi, M. Stepanova, F. Nader, D. Nelson, E. Lawitz, I.M. Jacobson, E. Gane, S.L. Hunt
Journal: Journal of Hepatology (2014)
Epidemic Listeriosis Associated with Mexican-Style Cheese
Authors: Michael J. Linnan, Laurene Mascola, Xiao Dong Lou, Veronique Goulet, Susana May, Carol Salminen, David W. Hird, M. Lynn Yonekura, Peggy Hayes, Robert Weaver, Andre Audurier, Brian D. Plikaytis, Shirley L. Fannin, Abraham Kleks, Claire V. Broome
Journal: New England Journal of Medicine (1988)

In Los Angeles County, California, 142 cases of human listeriosis were reported from January 1 through August 15, 1985. Ninety-three cases (65.5 percent) occurred in pregnant women or their offspring, and 49 (34.5 percent) in nonpregnant adults. There were 48 deaths: 20 fetuses, 10 neonates, and 18 nonpregnant adults. Of the nonpregnant adults, 98 percent (48 of 49) had a known predisposing condition. Eighty-seven percent (81 of 93) of the maternal/neonatal cases were Hispanic. Of the Listeria monocytogenes isolates available for study, 82 percent (86 of 105) were serotype 4b, of which 63 of 86 (73 percent) were the same phage type. A case-control study implicated Mexican-style soft cheese (odds ratio, 5.5; 95 percent confidence interval, 1.2 to 24.8) as the vehicle of infection; a second case-control study showed an association with one brand (Brand A) of Mexican-style soft cheese (odds ratio, 8.5; 95 percent confidence interval, 2.4 to 26.2). Laboratory study confirmed the presence of L. monocytogenes serogroup 4b of the epidemic phage type in Brand A Mexican-style cheese. In mid-June, all Brand A cheese was recalled and the factory was closed. An investigation of the cheese plant suggested that the cheese was commonly contaminated with unpasteurized milk. We conclude that the epidemic of listeriosis was caused by ingestion of Brand A cheese contaminated by one phage type of L. monocytogenes serotype 4b.