tbuckley/cabot-search huggingface dataset:
Intraperitoneal mitoxantrone in the treatment of recurrent ascites from progressive epithelial ovarian cancer.
Authors: M. Marinaccio, E. Mele, E. De Marino, R. Catacchio, C. Pellegrino, F. Sozzi, S. Schonauer
Journal: Journal of Clinical Oncology (2010)

5051 Background: In patients with epithelial ovarian cancer (EOC), progression of disease is often characterized by recurrent ascites that does not respond neither to antineoplastic drugs nor to repeated paracentesis. We evaluated the effect of Mitoxantrone (MTZ) administered intraperitoneum (i.p.) to obtain control of recurrent ascites in this particular subset of pts. Methods: Seventy-four patients (median age 59 yrs, range 39–76) with EOC who progressed with ascites after 3 (42/74), 4 (23/74) or 5 (9/74) previous lines of chemotherapy were treated with MTZ i.p. delivered through a temporary catheter (EasyCyst puncture set,Ch 12, RUSCH France). After removing all the ascitic fluid, the drug was infused at the dose of 20 mg/m2, diluted in 1,500 mL of normal saline, via a 60-minute i.p. instillation and then it was left in situ. All the patients were controlled every 28 days and treatment was repeated in the presence of new developed ascites.The response of ascites to MTZ, was measured according these response criteria: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Results: All patients were evaluable for toxicity and clinical response. A total of 169 28-day cycles were registered. We observed CR in 23/74 pts (31.1%), PR in 26/74 pts (35.1%), SD in 10/74 pts (13.5%), and PD in 15/74 pts (20.3%). Endoperitoneal tratment was generally well tolerated: 5 out of 74 pts complained of abdominal pain, well responding to paracetamol. Haematologial toxicity was grade I leukopenia (6/74 = 8.1%), grade I anemia (4/74 = 5.4%); non-haematological toxicity was nausea-vomiting (2.7%), diarrhoea (2.7%) and fever (4,1%). No cases of cardiotoxicity were reported even though 59/74 pts had been previously treated with anthracyclines. At the median follow-up of 52 months (range 6–102), the median lenght of response was 7 months (range 2-10). Conclusions: MTZ i.p. at a 20 mg/m2 dose by a temporary catheter is a safe, well tolerated and viable therapeutic option. The global response obtained (66.2% = 23/74 CR + 26/74 PR) means an important reduction of the quantity of ascites with a consequent reduction of paracentesis and demonstrates that MTZ i.p. improves quality of life in these patients. No significant financial relationships to disclose.
Mutational Landscape and Antiproliferative Functions of ELF Transcription Factors in Human Cancer
Authors: Mizuo Ando, Masahito Kawazu, Toshihide Ueno, Daizo Koinuma, Koji Ando, Junji Koya, Keisuke Kataoka, Takahiko Yasuda, Hiroyuki Yamaguchi, Kazutaka Fukumura, Azusa Yamato, Manabu Soda, Eirin Sai, Yoshihiro Yamashita, Takahiro Asakage, Yasushi Miyazaki, Mineo Kurokawa, Kohei Miyazono, Stephen D. Nimer, Tatsuya Yamasoba, Hiroyuki Mano
Journal: Cancer Research (2016)

ELF4 (also known as MEF) is a member of the ETS family of transcription factors. An oncogenic role for ELF4 has been demonstrated in hematopoietic malignancies, but its function in epithelial tumors remains unclear. Here, we show that ELF4 can function as a tumor suppressor and is somatically inactivated in a wide range of human tumors. We identified a missense mutation affecting the transactivation potential of ELF4 in oral squamous cell carcinoma cells. Restoration of the transactivation activity through introduction of wild-type ELF4 significantly inhibited cell proliferation in vitro and tumor xenograft growth. Furthermore, we found that ELF1 and ELF2, closely related transcription factors to ELF4, also exerted antiproliferative effects in multiple cancer cell lines. Mutations in ELF1 and ELF2, as in ELF4, were widespread across human cancers, but were almost all mutually exclusive. Moreover, chromatin immunoprecipitation coupled with high-throughput sequencing revealed ELF4-binding sites in genomic regions adjacent to genes related to cell-cycle regulation and apoptosis. Finally, we provide mechanistic evidence that the antiproliferative effects of ELF4 were mediated through the induction of HRK, an activator of apoptosis, and DLX3, an inhibitor of cell growth. Collectively, our findings reveal a novel subtype of human cancer characterized by inactivating mutations in the ELF subfamily of proteins, and warrant further investigation of the specific settings where ELF restoration may be therapeutically beneficial. Cancer Res; 76(7); 1814-24. ©2016 AACR.
P0144 : Two testing strategies for covert hepatic encephalopathy diagnosis stabilizes agreement between sites in a multi-center analysis: validation of the EASL/AASLD he guidelines
Authors: S. Allampati, A. Duarte-Rojo, L. Thacker, M. White, A. Unser, E. Gavis, J. Hovermale, D.M. Heuman, B. John, J.S. Klair, C. Flud, R. O'Shea, J.S. Bajaj
Journal: Journal of Hepatology (2015)
Paternal Psychological Stress Reprograms Hepatic Gluconeogenesis in Offspring
Authors: Ling Wu, Yan Lu, Yang Jiao, Bin Liu, Shangang Li, Yao Li, Fengying Xing, Dongbao Chen, Xing Liu, Jiejie Zhao, Xuelian Xiong, Yanyun Gu, Jieli Lu, Xuejin Chen, Xiaoying Li
Journal: Cell Metabolism (2016)
Dasatinib lack of cross intolerance to imatinib in patients (pts) with chronic myelogenous leukemia chronic phase (CML-CP) intolerant to imatinib: a retrospective analysis of safety
Authors: H. J. Khoury, S. L. Goldberg, M. J. Mauro, R. M. Stone, Y. Matloub, T. Chen, F. Guilhot
Journal: Journal of Clinical Oncology (2008)

7015 Background: Dasatinib is a second generation BCR-ABL inhibitor structurally unrelated to imatinib. Dasatinib is effective in CML-CP patients intolerant of imatinib and is generally well-tolerated. Fluid retention, gastrointestinal intolerance, and myelosuppression are the most common adverse events (AE) and are dose and schedule dependent. These analyses were undertaken to explore whether the type of intolerance to imatinib predicts the safety of dasatinib. Methods: Data from two multicenter studies in CML-CP (one Phase II and one Phase III) were pooled. Intolerance to imatinib was defined as ≥ Grade 3 non-hematologic toxicity and/or Grade 4 hematologic toxicity lasting > 7 days. Dasatinib doses were 70 mg BID, 50 mg BID, 100 mg QD and 140 mg QD. Median duration of dasatinib therapy was 11.96 mos (0.03–30.06 mos). Discontinuations due to NCI-CTCAE Grade 3–4 toxicities were used to assess cross intolerance between imatinib and dasatinib. Correlation between pleural effusions on dasatinib and fluid retention on imatinib was assessed. Results: A total of 271 imatinib-intolerant CML-CP patients (pts) were included. Duration of imatinib therapy was < 1year in 58% of pts. Imatinib intolerance (im- I) was hematologic in 46 pts and non-hematologic in 225 pts (exact cause known in 210 pts.). A total of 9 (4%) pts experienced the same Grade 3–4 non-hematologic toxicity on dasatinib as on imatinib and only 2 (1%) discontinued dasatinib; the other 7 pts continued dasatinib after dose reduction. Of the 10 pts with fluid retention on imatinib, none developed pleural effusion on dasatinib. Among the 46 pts who discontinued imatinib for hematologic toxicity, 6 (13%) discontinued dasatinib because of cytopenia. Conclusion: There was no evidence of cross-intolerance between imatinib and dasatinib in this large population of imatinib-intolerant CML-CP pts. Intolerance AEs Imatinib (# im-I) Dasatinib (# Grade 3–4) Dasatinib (# discontinued) Rash 87 3 1 Hepatotoxicity 48 0 0 Myalgia/arthralgia 22 1 1 GI toxicity 15 2 0 Fluid retention 10 0 0 Pulmonary toxicity 10 0 0 Bone pain 5 0 0 Others (1 or 2 pts each) 13 3* 0 Alltoxicities 210 9 2 * Fatigue, headache and cardiac toxicity Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb, Novartis
SERIES ‘‘THE GLOBAL BURDEN OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE’’ #3: The global burden of COPD: the natural history of COPD
Authors: David M. Mannino, G. Watt, D. Hole, C. Gillis, C. Hart, A. McCormachie, G. D. Smith, M. Upton, V. Hawthorne, D. D. Sin, S. F.P. Man, S. Van Eeden, D. W. Mapel, J. Vestbo
Journal: European Respiratory Journal (2006)
Estimating the real cost of adjuvant (adj) trastuzumab (T) in patients (pts) with HER-2+ (H+) early stage breast cancer (ESBC): Potential impact of reduced use of expensive oncology drugs (EOD) in metastatic breast cancer (MBC)
Authors: R. O'Cearbhaill, E. Wilson, A. deFrein, Z. Qadir, D. McDonnell, J. Crown
Journal: Journal of Clinical Oncology (2007)

6534 Background: Pts with H+ early stage BC have an approximately 35% risk of developing MBC (BCIRG001). T has been reported to reduce this risk by 33–50%, but costs approximately €;30k per pt, a burden some health systems deem unsustainable. This risk reduction might however result in decreased utilization of EOD in MBC, lowering the societal cost of adjT. We attempted to estimate the cost per relapse prevented (Crp), and the real cost of adjT, allowing for potential savings in prevented cases of MBC. Methods: We conducted a retrospective analysis of the mean cost per pt of AdjT (1 year) and of EOD in MBC in St. Vincent's University Hospital. We devised an equation to calculate the Crp for adj T. C rp =[A-M(NR A /10 4 )]/[NR A /10 4 ] where A = cost per pt for adjT, M = EOD cost per pt with MBC, N = % of pts relapsing after standard adj treatment, R A = % reduction in the risk of relapse after adjT (over standard adj). Results: H+ pts with MBC received T (average 34 cycles €;2,400 each) with a combination of the following drugs: docetaxel (x8 €;1,500), gemcitabine (x5 €;1,215), capecitabine (x8 €;400), vinorelbine ( x19 €;187). Only 2 pts received bevacizumab (Bev) (x15 €;3,000). In our unit the mean EOD cost per pt with MBC was €;108k. The cost per relapse prevented for a 33% and a 50% reduction in relapse rate would be €;152k and €;63k, respectively. Furthermore, assuming a 50% reduction in the rate of relapse (from 35 to 17.5%) the real cost of adjT per pt treated is not €;30k, but approximates €;11k (€;30k×100-{17.5x €;108k}). Conclusions: The reduced utilization of EOD in MBC likely has a very beneficial impact on the societal cost of adjT. Confirmation of the efficacy of shorter adjT (e.g. FinnHer) would produce further benefit. The increasing use of novel EOD in MBC e.g. Bev would make adjT even more cost-effective. No significant financial relationships to disclose.
Characteristics and disposition of persons found not guilty by reason of insanity in New York State, 1971-1976
Authors: R A Pasewark, M L Pantle, H J Steadman
Journal: American Journal of Psychiatry (1979)

In order to develop an empirical profile of persons acquitted by reason of insanity from which policy could be developed, the authors studied all acquittals in New York State from 1971-1976. During this period 196 men and 29 women were found not guilty by reason of insanity. In contrast to adults admitted to state correctional facilities, the study group contained proportionately more persons who were white and older. The most frequent crimes for which subjects were tried were homicide, assault, and robbery. Most victims were acquaintances of the defendants. By 1976, 67 persons had been discharged after hospitalization ranging from 1 to 1,235 days. These defendants are still being followed after their return to the community.
Epidemiologic and laboratory surveillance of the measles outbreak in the Federation of Bosnia and Herzegovina, February 2014–April 2015
Authors: I. Salimović-Bešić, M. Šeremet, J.M. Hübschen, M. Hukić, N. Tihić, S. Ahmetagić, Z. Delibegović, A. Pilav, M. Mulaomerović, J. Ravlija, C.P. Muller, A. Dedeić-Ljubović
Journal: Clinical Microbiology and Infection (2016)
Timely Modulation of Cardiac Output by a Pacemaker Can Stabilize Induced Periodic Breathing
Authors: R Baruah, A Giannoni, K Willson, CH Manisty, M Fontana, Y Mebrate, H Yadav, B Unsworth, A Kyriacou, S Sen, R Sutton, P Kanagaratnam, AD Hughes, J Mayet, DP Francis
Journal: Circulation (2010)
Attempts to ban DDT have increased deaths
Authors: Annabel Ferriman
Journal: BMJ (2001)

Pressures on poor countries to ban the insecticide DDT because of fears that its use would harm the environment have led to a resurgence of malaria in the world, yet the environmental impact of its use are “negligible,” a study published this week has said.

The study shows that after malaria was eradicated in wealthy countries and DDT was banned in those places, poor countries were pressured by health and donor agencies and environmental groups to stop using DDT spraying programmes. The agencies feared that they would harm the environment and adversely affect human health.

But these fears were unsubstantiated, the study's authors believe. “No scientific peer reviewed study has ever replicated any case of negative human health impacts from DDT,” said Dr Roger Bate, media and development director for the International Policy Network and joint author of the study with Richard Tren, director of economic policy at the non-governmental organisation Africa Fighting Malaria.


A surge in malaria in the KwaZulu-Natal province of South Africa coincided with the withdrawal of DDT from malaria control programmes in 1996. Synthetic pyrethroids were used in its place. But some mosquitoes, most notably the Anopheles funestus, which is a highly efficient vector of the disease, had developed resistance to these chemicals, and when it returned to South Africa in the second half of the 1990s, malaria rates began to increase.
Sensorimotor functions and cognitive disturbance in psychiatric patients
Authors: G J Tucker, E W Campion, P M Silberfarb
Journal: American Journal of Psychiatry (1975)

The authors studied 109 consecutive admissions to an acute psychiatric unit in a general hospital to determine the relationship of specific sensorimotor impairments to cognitive disturbance. The results indicated a strong but not exclusive correlation between neurological impairment and thought disorder as well as between neurological impairment and schizophrenia. The theoretical and etiological implications are discussed, as well as the relationship of these findings to other variables.
Adenocarcinoma of the lower esophagus with Barrett’s or without Barrett’s: differences in patients survival after preoperative chemoradiation
Authors: P. Cen, J. A. Ajani, A. M. Correa, J. H. Lee, D. M. Maru, S. Anandasabapathy, Z. Liao, W. L. Hofstetter, S. G. Swisher, R. Komaki, W. A. Ross
Journal: Journal of Clinical Oncology (2008)

4524 Background: It is unclear whether the overall survival (OS) of patients with localized esophageal adenocarcinoma (LEA) with Barrett’s (Barrett’s-positive) and those with LEA without Barrett’s (Barrett’s-negative) following preoperative chemoradiation is different. Based on the anticipated differences in biology, we hypothesized that the two groups will have a different OS, if a large cohort is analyzed. Methods: In this retrospective analysis, patients with LEA who had preoperative chemoradiation and surgery were selected. Apart from age, gender, baseline clinical stage, location, class of cytotoxics, post-therapy stage, and OS; LEAs were divided up in the Barrett’s-positive and Barrett’s-negative groups. The Kaplan-Meier and Cox-regression analytic methods were used. Results: We analyzed 362 patients with LEA (137 Barrett’s-positive and 225 Barrett’s-negative). A higher proportion of Barrett’s-positive patients had EUST2 cancers (27%) than those with Barrett’s-negative cancer (17%). More Barrett’s-negative LEAs involved gastroesophageal junction than Barrett’s-positive ones (p=0.001). The OS was significantly shorter for Barrett’s-positive patients than that for Barrett’s-negative patients (32 months vs. 51 months; p=0.04). In a multivariate analysis for OS, Barrett’s-positive LEA (p=0.006), old age (p=0.016), baseline positive nodes (p=0.005), more than 2 positive ypN (p=0.0001), higher ypT (p=0.003), and the use of a taxane (0.04) were the independent prognosticators. Conclusions: This is the largest cohort of patients with LEA to demonstrate that the clinical biology (reflected by the difference in OS) is less favorable for patients with Barrett’s-positive LEA than that for patients with Barrett’s-negative LEA undergoing preoperative chemoradiation. No significant financial relationships to disclose.
Abstract 14359: Abnormal Extracellular Matrix Remodeling in an Nkx2-5+/- Model of Dilated Cardiomyopathy
Authors: Brett S Harris, Jeffrey A Jones, Catalin F Baicu, Risha K Patel, Mary S Rackley, Michael R Zile, Rupak Mukherjee, Terrence X O'Brien
Journal: Circulation (2012)

Mice heterozygous for the cardiac transcription factor Nkx2-5 are viable but have an abnormal conduction system. To identify conduction cells we employed a double transgenic strategy by crossing Nkx2-5 +/-  mice with a knock-out/knock-in Connexin 40 (Cx40) allele replaced with enhanced green fluorescent protein (EGFP)(Cx40 EGFP/+ ). We subjected both the Nkx2-5 +/-  and Nkx2-5 +/- /Cx40 EGFP/+  mice to 4 weeks of pressure-overload (PO) via transaortic constriction and found the left ventricle (LV) responded with a reproducibly dilated cardiomyopathy phenotype in contrast to the LV hypertrophy and preserved function in Cx40 EGFP/+  and wild-type controls (EF declined to 40-42% with associated dysynchrony). To elucidate mechanisms underlying the dilated phenotypes found in Nkx2-5 cohorts, mRNAs were analyzed by specialized gene chip arrays. We found no significant differences in markers of apoptotic, growth and transcription factor genes unrelated to Nkx2-5. However, there were marked and significant abnormalities of genes known to regulate the extra-cellular matrix (ECM) including increased metalloproteinase (MMP) -2(+3.1 fold) and MMP-14 (+12.5 fold) and decreases in tissue inhibitor of metalloproteinase (TIMP) -3 (-76.6 fold) and TIMP-4 (-3.7 fold). Confirmatory MMP-2 zymography showed the active form increased 5.8 fold. There were also changes identified within the ECM with increases in cardiac fibroblast specific collagen type 1a (+57.6 fold) and 5a (+7.5 fold). Immunofluorescence imaging for collagen 1a after PO in the WT mice showed high levels typical for myocardial fibrosis but the dilated Nkx2-5 +/- /Cx40 EGFP/+  transgenic failed to mount a fibrotic collagen response and was confirmed with picro sirius red staining for total collagen. Finally, we found gene expression was decreased for Smad1 (-16-fold), -5 (-5.9-fold) and -7 (-24-fold) with corresponding increases in latent TGF-β binding protein-1 (+3.3-fold) and -2 (+56-fold), compared to controls, suggesting that perturbed Smad/TGF-β signaling may underlie the dilated Nkx2-5 +/- /Cx40 EGFP/+  phenotype. ECM remodeling is a component of heart failure syndromes. Our data suggest cardiomyocytes lacking Nkx2-5 are unable to correctly signal to the ECM after PO.
Status of geriatric oncology in India: A national multicentric survey of oncology professionals
Authors: B. Arora, P. M. Parikh, R. Nair, A. Vora, S. Gupta, P. Sastry, H. Menon, A. Bakshi, P. Kumar, L. Goyal
Journal: Journal of Clinical Oncology (2006)

16035 Background: Elderly cancer patients are underrepresented in cancer services utilization and clinical research in India. National data on providers’ knowledge, attitude and practices with regard to elderly cancer patients is sparse and is urgently required to address needs of this vulnerable and growing population. Methods: A self administered questionnaire was mailed to nationally representative sample of practicing oncologists all over India. 112 Oncologists (Medical Oncologists-51%; Radiation Oncologists-25%; Surgical Oncologists-20%; allied fields-4%) responded out of 250 mailed Questionnaires. Results: A designated Geriatric Oncology unit is in existence in very few (&lt;5%) centers. Majority (51%) considered patients with chronological age of &gt;60 years as elderly for India. Although 75% of elderly patients receive some therapy, only 50% of potentially curable patients and a similar percentage of potentially incurable patients receive standard of care. Also, 50% patients require modification in their treatment and only two-third of treated patients complete therapy. The existent barriers to treatment included poor performance status (53%), advanced stage (16%), and co-morbidities (15%). Only 51% Oncologists always discussed and 28% always enrolled elderly patients in clinical trials. Standard of care and evidence based recommendations for elderly patients were felt to be lacking by 49% and 92% of respondents respectively. The need of separate trials for elderly and a separate discipline of Geriatric Oncology was voiced by 93% and 89% of respondents respectively. Major differences in treatment practice between medical oncologists and non medical oncologists are shown in table . Conclusions: Treatment practices and accrual of elderly cancer patients in clinical trials in India is far from optimal. Formation of a National Geriatric Oncology society and creation of designated Geriatric oncology services at key centers may enhance the understanding and clinical care of this population. [Table: see text] No significant financial relationships to disclose.
Cancer mortality in cohorts of workers in the European rubber manufacturing industry first employed since 1975
Authors: M. Boniol, A. Koechlin, B. Świątkowska, T. Sorahan, J. Wellmann, D. Taeger, K. Jakobsson, E. Pira, P. Boffetta, C. La Vecchia, C. Pizot, P. Boyle
Journal: Annals of Oncology (2016)
Relief of obstructive jaundice from pancreatic cancer: the end of the plastic stent era?
Authors: Todd H Baron, Ian S Grimm
Journal: Gut (2015)

Initially described by Soehendra and Reynders-Frederix1 in 1980, plastic stents have been widely used for endoscopic relief of malignant biliary obstruction. The relative ease of placement and removal of plastic stents, as well as their low cost, have made them an attractive option for the past 35 years. It has been apparent for decades, however, that self-expandable metal stents (SEMS) provide much more durable biliary drainage than plastic stents. Accumulating evidence now suggests that it may no longer be justifiable to use plastic stents when it is clear that metal stents are associated with superior outcomes, fewer adverse events (AEs) and fewer repeated interventions.2 These advantages, along with reductions in length of hospital stay, appear to fully offset the high initial cost of selecting an SEMS over a plastic stent for palliation of malignant distal biliary obstruction—even in patients whose projected life expectancy is limited.3 ,4 In patients with borderline resectable pancreatic cancer who are undergoing neoadjuvant therapy, SEMS have also …