tbuckley/cabot-search huggingface dataset:
Abstract 2024: BP1 homeoprotein induces tumor cell growth and estrogen-independent tumorigenesis in mice
Authors: Sidney W. Fu, Saurabh Kirolikar, Erika Ginsburg, Arnold Schwartz, Samuel Simmens, Patricia E. Berg
Journal: Cancer Research (2016)

Abstract BACKGROUND. BP1 is a member of the homeobox gene family of transcription factors. Our recent studies have shown that BP1 overexpression increases cell survival, aggressiveness and metastasis in breast cancer cells. BP1 protein is expressed in 80% of invasive ductal breast tumors, including 100% of ER negative (ER-) tumors and 73% of ER positive (ER+) tumors. Therefore we hypothesize that BP1 may regulate ER in breast cancer. A mouse model was developed to test the regulatory effects of BP1 in ER expression. MATERIALS AND METHODS. MCF-7 breast cancer cells transfected with BP1 or vector control were njected into the fat pads of nude mice. Regulation of ER by BP1 was studied using ChIP assays; EMSA assays were used to test binding of BP1 to ER DNA. Tamoxifen assays were used to evaluate the effects of BP1 overexpression on tamoxifen resistance. RESULTS. MCF-7 cells overexpressing BP1 or control cells containing an empty vector were injected into nude mice. Approximately half of the estrogen-supplemented mice developed tumors. Although MCF-7 cells require exogenous estrogen to form tumors in nude mice, approximately 20% of the mice implanted with cells overexpressing BP1 were able to form tumors in the absence of added estrogen. To understand the molecular mechanisms of this observation, we carried out in vitro experiments. Our data suggest that BP1 regulates ER both directly and indirectly: (1) Direct: ChIP assays and EMSA assays showed that BP1 binds to the first intron of the ER alpha gene and transcriptionally activates it, leading to increased ER protein. (2) Indirect: regulation of ER also occurs indirectly by BP1 upregulation of p300, an activator of ER, and also by repression of BRCA1 by BP1; BRCA1 destabilizes ER protein. Furthermore, MCF-7 cells overexpressing BP1 are more resistant to growth in 3uM tamoxifen compared with empty vector containing cells. CONCLUSIONS. BP1 overexpression in MCF-7 cells injected into mice not only increases tumor size but also promotes estrogen-independent tumorigenesis, and leads to resistance to tamoxifen. Therefore, BP1 could serve as a novel therapeutic target for ER+ breast cancer. Citation Format: Sidney W. Fu, Saurabh Kirolikar, Erika Ginsburg, Arnold Schwartz, Samuel Simmens, Patricia E. Berg. BP1 homeoprotein induces tumor cell growth and estrogen-independent tumorigenesis in mice. [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 2024.
Prediction models of smoking cessation in lung and head and neck cancer patients: Role of second-hand smoke (SHS) exposure.
Authors: Geoffrey Liu, Yuyao Song, Devon Alton, Tom Yoannidis, Robin Milne, Samantha Sarabia, Zahra Merali, Steven Habbous, M Catherine Brown, Ashlee Vennettilli, Andrew J. Hope, Doris Howell, Jennifer M. Jones, Peter Selby, David Paul Goldstein, Meredith Elana Giuliani, Wei Xu, Lawson Eng
Journal: Journal of Clinical Oncology (2015)

9591 Background: Some cancer survivorship programs incorporate components of healthy lifestyle behavior modification. We evaluated the role that various clinical variables and smoking habits play in predicting which cancer survivors are more likely to quit smoking. Such knowledge may help with resource allocation within these programs. Methods: We focused on lung cancer (LC) and head and neck cancer (HNC) patients as these have the highest active smoking rates among all cancer sites at Princess Margaret Cancer Centre. Patients from 2006-12 completed questionnaires at diagnosis (baseline) and follow-up (median 2 years apart) that assessed smoking status. Baseline clinical and demographic information was obtained. Multivariate logistic regression analysis evaluated the association of smoking and clinical variables at diagnosis to subsequent smoking cessation. Predictive models were assessed for their discriminatory capabilities (concordance-index or area under the curve, AUC). Results: In this cohort, 261/731 LC and 145/450 HNC patients smoked at diagnosis; subsequent overall quit rates were 69% and 50% respectively. Univariate factors associated with smoking cessation included having LC (p = 0.001), being married (p = 0.02), having at least completed secondary school (p = 0.049), having less cumulative smoking (pack-years; p = 0.004), and having adequate social support (p = 0.009). In multivariate modeling, fewer pack-years, having LC and being married remained significant and this predictive model was associated with moderate predictive ability (AUC 0.68 [95% CI: 0.62-0.73]. However, the addition of either SHS household exposure (AUC 0.76 [0.71-0.81]) or spousal smoking (AUC 0.77 [0.71-0.82]) further improved the predictive model. The addition of SHS variables in other exploratory predictive models of smoking cessation improved those models in a similar manner. Similar improvements in prediction were seen in subgroup analysis of LC and HNC. Conclusions: SHS exposure significantly improves the predictive abilities to determine which patients who smoked at their cancer diagnosis would subsequently quit. Cessation programs may benefit from allocating resources accordingly.
A Deletion Of About 11kb Starting From 0.5 Kb 5’ To The β-Globin Gene Reactivates Foetal Haemoglobin and Leads To β Thalassemia Intermedia When Associated To a β-Zero Thalassemic Mutation
Authors: Photis Beris, Tanguy Araud, Lorella Clerici, Anne-Pascale Grandjean, Georgios Georgiou, Frédéric Guerry, Kaveh Samii, Pierre-Alain Menoud
Journal: Blood (2013)
Health-related quality of life (HRQoL) in patients with advanced, nonfunctional, well-differentiated gastrointestinal (GI) or lung neuroendocrine tumors (NET) in the phase 3 RADIANT-4 trial.
Authors: Marianne E. Pavel, Jonathan R. Strosberg, Lida Bubuteishvili-Pacaud, Evgeny Degtyarev, Maureen Neary, Matthias Hunger, Jennifer Eriksson, Nicola Fazio, Matthew H. Kulke, Simron Singh, James C. Yao
Journal: Journal of Clinical Oncology (2016)

e15657 Background: In RADIANT-4, everolimus (EVE) + best supportive care (BSC) improved progression-free survival (PFS) vs placebo (PBO) + BSC in 302 patients with advanced, progressive, nonfunctional GI or lung NET (Yao Lancet 2015). We report prespecified and post hoc analyses to assess treatment effect on HRQoL. Methods: HRQoL was measured with FACT-G, a 27-item validated questionnaire with 4 domains: physical (PWB), social/family (SWB), emotional (EWB), and functional wellbeing (FWB). FACT-G was completed at baseline and every 8 wks until mo 12, then every 12 wks. Time to definite deterioration (TDD) of ≥ 7 points (minimal important difference, MID) in FACT-G total score (range 0-108) was a prespecified secondary trial endpoint analyzed with Kaplan-Meier method and Cox model to derive the hazard ratio (HR). Post hoc analyses included TDD for FACT-G subscale scores using ≥ 3 point MID and linear mixed models (LMM) fitted to FACT-G total and subscale scores, assuming missing observations were random. In sensitivity analyses, pattern mixture models (PMM) were fitted, assuming missing data were not random. Results: In prespecified analyses, no statistically significant differences were observed between the treatment arms in TDD of FACT-G total score (HR: 0.81 [95% CI: 0.55, 1.21]), numerically favoring EVE. In post hoc analyses, TDD of PWB, SWB, EWB, and FWB subscale scores were also maintained for EVE vs PBO; HRs 1.01 (95% CI: 0.69, 1.53), 0.72 (95% CI: 0.45, 1.28), 0.57 (95% CI: 0.36, 0.93), and 0.94 (95% CI: 0.60, 1.46), respectively. In LMM, FACT-G total score at wk 8 was 79.5 (95% CI: 77.7, 81.3) for EVE and 80.0 (95% CI: 77.6, 82.5) for PBO, declining to 75.7 (95% CI: 73.2, 78.2) and 77.8 (95% CI: 73.5, 82.1) at wk 48. PMM confirmed robustness of LMM results. Conclusions: Analyses of FACT-G total score showed that in addition to PFS benefits, HRQoL is maintained, with no statistically or clinically relevant differences, in patients with advanced, nonfunctional, well-differentiated GI or lung NET receiving EVE vs PBO, despite usual toxicities of active cancer treatment. Analyses for each of the 4 FACT-G domains showed consistent results.
The chaperone co-inducer BGP-15 alleviates ventilation-induced diaphragm dysfunction
Authors: Heba Salah, Meishan Li, Nicola Cacciani, Stefano Gastaldello, Hannah Ogilvie, Hazem Akkad, Arvind Venkat Namuduri, Valeria Morbidoni, Konstantin A. Artemenko, Gabor Balogh, Vicente Martinez-Redondo, Paulo Jannig, Yvette Hedström, Barry Dworkin, Jonas Bergquist, Jorge Ruas, Laszlo Vigh, Leonardo Salviati, Lars Larsson
Journal: Science Translational Medicine (2016)

BGP-15 reduces ventilation-induced diaphragm dysfunction by improving diaphragm fiber and myosin function and enhancing mitochondrial activity.
A highly specific and sensitive hepatitis C virus antigen enzyme immunoassay for One‐step diagnosis of viremic hepatitis C virus infection
Authors: Ke‐Qin Hu, Wei Cui
Journal: Hepatology (2016)

The current standard in diagnosing hepatitis C virus (HCV) infection requires two sequential steps: anti-HCV test to screen, followed by HCV RNA reverse-transcription polymerase chain reaction to confirm viremic HCV (V-HCV) infection. HCV core antigen tests provided potential for possible one-step diagnosis. However, low sensitivity and specificity limit their clinical utility. The present study developed a novel HCV antigens enzyme immunoassay (HCV-Ags EIA) and assessed its sensitivity, specificity, and utility for one-step diagnosis of V-HCV infection using 365 serum specimens, including 176 without and 189 with V-HCV infection. First, we confirmed the presence of HCV nonstructural proteins 3, 4b, and 5a besides HCV core antigen during HCV infection and developed a novel HCV-Ags EIA through simultaneous detection of all four HCV proteins. For the first time, the present study demonstrated that serum sample denaturation decreases the test specificity due to release of HCV-Ags sequestered in HCV immune complexes and should not be used in any HCV-Ags, including all the current HCV core antigen assays. On the other hand, using sample nondenaturation, the HCV-Ags EIA results showed 98.9% specificity and 100% sensitivity compared to serum anti-HCV and HCV RNA reverse-transcription polymerase chain reaction results. Using serum sample dilution, and nondenaturation, the lowest limits of detection of the HCV-Ags EIA were equivalent to serum HCV RNA levels of approximate 150-250 IU/mL.The highly specific and sensitive HCV-Ags EIA developed in the present study has the lowest limit of detection equivalent to serum HCV RNA levels of 150-250 IU/mL; using nondenaturation of serum samples, our HCV-Ags EIA reliably differentiated V-HCV infection from resolved HCV infection, accomplishing screening and diagnosis of V-HCV infection in one step. (Hepatology 2016;64:415-424).
Case 44-1964
Authors: Lamar Soutier, Austin L. Vickery
Journal: New England Journal of Medicine (1964)

Presentation of Case*A fifty-six-year-old professor of law entered the hospital because of dyspnea and pain in the chest.He had been well until five years previously, when he experienced several episodes of "tightness" in the chest unrelated to effort. Thereafter he occasionally had pain in the neck that was not relieved by nitroglycerin. One month before admission he noticed a "stitch" in the right lower portion of the chest anteriorly that was aggravated by deep breathing; analgesics afforded temporary relief. Two weeks later the pain recurred and progressed in severity, and three days before entry dyspnea developed.Twenty years . . .
Abstract 2195: Small molecule drug conjugates targeted to cholecystokinin 2 receptors
Authors: Jyoti Roy, Charity Wayua, Philip S. Low
Journal: Cancer Research (2016)

Abstract Cholecystokinin 2 receptor (CCK2R) is over expressed on many cancers of lungs, pancreas, liver and GI tract (esophagus, colon and GIST), whereas its expression in normal tissues is limited to epithelial cells of the GI tract and brain. This restricted expression pattern renders CCK2R an excellent candidate for use in tumor-targeted drug delivery. Here we used a high affinity, low molecular weight CCK2R antagonist (CRL) to deliver imaging agents and cytotoxic drugs specifically to CCK2R positive tumors. We demonstrated that in vitro CRL conjugated to either NIR dye or radioactive imaging agent binds selectively to CCK2R positive cancer cells and exhibits low nano molar affinity for the receptor. We further showed that In vivo NIR dye and radiolabeled conjugate localizes primarily to the CCK2R positive murine tumor xenografts. Both of these conjugates also exhibited low serum protein binding and cleared rapidly from blood. Thus CRL-NIR dye conjugate have a potential application in fluorescence guided surgery where as CRL-radioactive conjugate seems promising for radioimaging in the clinic. Encouraged by the results of the imaging agents, CRL was conjugated to two potent microtubule inhibitors (tubulysin B hydrazide and desacetyl vinblastine). In vitro these two conjugates demonstrated high affinity and specificity for CCK2R. In vivo CRL conjugated to tubulysin B hydrazide was found to be more effective in eliminating tumor compared to desacetyl vinblastine conjugate. Neither of the CRL-cytotoxic drug conjugates showed any toxicity associated with the base drug nor any weight loss was observed in the mice treated with these conjugates. Results suggest that CRL has the proficiency to delivery drug specifically to tumors over expressing CCK2R receptor and lower the toxicities associated with conventional ways of treating cancer. Citation Format: Jyoti Roy, Charity Wayua, Philip S. Low. Small molecule drug conjugates targeted to cholecystokinin 2 receptors. [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 2195.
Conditioning with Fludarabine, BCNU, and Melphalan in Allogeneic Stem Cell Transplantation Results in Reduced Toxixcity and High Activity Against Advanced Hematologic Malignancies.
Authors: Reinhard Marks, Karin Potthoff, Joachim Hahn, Gabriele Ihorst, Hartmut Bertz, Alexandros Spyridonidis, Ernst Holler, Jurgen Finke
Journal: Blood (2007)
Radiation necrosis crossing the tentorium or falx: Five case reports.
Authors: J. J. Graber, L. M. DeAngelis
Journal: Journal of Clinical Oncology (2010)

e12535 Background: After patients receive radiation therapy to the brain, new areas of enhancement may be tumor or radiation necrosis. Radiologic findings are not definitive and treatment and prognosis differ substantially. We present 5 patients who had necrosis after radiation, all of which were remote from the site of maximum radiation dose and separated from it by physical barriers of the tentorium or sagittal sinus. Methods: Case series identified by physician recall. Results: Five patients, ages 43-76 (mean 58.6), developed enhancing lesions of the brain opposite the tentorium (n = 3) or sagittal sinus (n = 2) from a site of prior radiation for tumor (breast cancer brain metastases [BM] [n = 2], lung cancer BM [n = 1], recurrent meningioma [n = 1], glioblastoma [n = 1]). The patient with glioblastoma received 60 Gy with concurrent temozolomide. The other 4 pts all received stereotactic radiosurgery (SRS) (18-20 Gy) and 3 also received external beam radiation 37.5 Gy in two and 6 Gy in one. Necrosis did not develop at the original site in 4 patients but first appeared on the opposite side of the tentorium in 3 pts and across the falx in 1. One patient had radiation necrosis at her originally radiated site as well as across the sagittal sinus. Necrosis developed between 13-29 (mean 20.4) months after radiation therapy, and was confirmed by pathology on resection (n = 1), hypometabolism (n = 2) or absence of hypermetabolism (n = 1) on PET, and clinical follow up without progressive growth (n = 5). Only three patients were clinically symptomatic, two of whom improved with dexamethasone. All five patients remained free of recurrent tumor growth at last follow up mean 67.4 (48-84) months from their original diagnoses, mean of 62.6 (36-82) months after receiving radiation and mean 47 (24-59) months after radiation necrosis first developed. Conclusions: Radiation necrosis may occur at sites remote from the maximal dose of RT delivered, even across physical barriers represented by tentorium or the sagittal sinus. No significant financial relationships to disclose.
Rationnel et design des essais européens pour la surveillance endoscopique après polypectomie
Authors: N. Musquer
Journal: Endoscopy (2016)

Nos stratégies de surveillance post-polypectomie sont-elles justifiées? C’est en substance la question à laquelle souhaitent répondre ces études. Cet article présente en effet le schéma de 3 études européennes multicentriques de grande ampleur à venir. Les investigateurs ont pour objectifs de proposer des stratégies de surveillance post-polypectomies plus adaptées et surtout de mieux documenter, grâce à ces essais, les stratégies actuelles reposant pour beaucoup selon eux sur des consensus d’experts avec un niveau de preuve parfois faible.
The BCL-2 Inhibitor ABT-199 (GDC-0199) in Combination with Bendamustine and Rituximab in Patients with Relapsed or Refractory Non-Hodgkin’s Lymphoma
Authors: Sven de Vos, Christopher R. Flowers, Ding Wang, Lode J. Swinnen, Nathan Fowler, Erin Reid, Maryella Gifford, Diane D'Amico, Martin Dunbar, Ming Zhu, Jianning Yang, Sari H. Enschede, Justin L. Ricker, David Chien, Rod A. Humerickhouse, Mark Kozloff
Journal: Blood (2014)
Vorinostat Induced Cellular Stress Disrupts the Balance Between p38 MAPK and Erk Pathways Leading to Apoptosis in WM Cells.
Authors: Jenny Sun, Hsiuyi Tseng, Lian Xu, Zachary Hunter, Bryan Ciccarelli, Mariateresa Fulciniti, Guang Yang, Ping Gong, Yangsheng Zhou, Xia Liu, Nikhil C. Munshi, Christopher J Patterson, Steven Treon
Journal: Blood (2009)
Influence of age on mechanisms and prognosis of heart failure
Authors: C. V. Hughes, M. Wong, G. Johnson, J. N. Cohn
Journal: Circulation (1993)

Background. Advanced age is commonly thought to carry a poor prognosis in congestive heart failure, but the case has not been established. The Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials (V-HeFT I and II) provided a large data base to assess the effect of age on hemodynamic profiles and survival in the failing heart. Methods and Results. Patients were stratified into four categories according to age: ≤55, 56-60, 61-65, and >65 years. The distributions of treatments and baseline characteristics from history, physical findings, and laboratory data were analyzed for differences across age categories. Survival curves were calculated for age strata according to treatment, presence or absence of coronary artery disease, ejection fraction, and peak oxygen consumption
Abstract 2661: The genomic landscape and clinical relevance of A-to-I RNA editing in human cancers
Authors: Han Liang
Journal: Cancer Research (2016)

Abstract Adenosine-to-inosine (A-to-I) RNA editing is a widespread post-transcriptional mechanism, but its genomic landscape and clinical relevance in cancer have not been investigated systematically. We characterized the global A-to-I RNA editing profiles of &amp;gt;6000 patient samples of 20 cancer types from The Cancer Genome Atlas and revealed a striking diversity of altered RNA-editing patterns in tumors relative to normal tissues. We identified an appreciable number of clinically relevant editing events, many of which are in noncoding regions. We experimentally demonstrated the functional effects of several RNA editing events and provide the evidence that RNA editing could selectively affect drug sensitivity. These results highlight RNA editing as an exciting theme for investigating cancer mechanisms, biomarkers and treatments. Citation Format: Han Liang. The genomic landscape and clinical relevance of A-to-I RNA editing in human cancers. [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 2661.
Long-term results of the French randomized trial comparing neoadjuvant chemotherapy followed by surgery versus surgery alone in resectable non-small cell lung cancer.
Authors: V. Westeel, B. J. Milleron, E. A. Quoix, M. Puyraveau, D. Moro-Sibilot, D. Braun, B. Lebeau, E. Lemarié, D. Debieuvre, A. G. Depierre
Journal: Journal of Clinical Oncology (2010)

7003 Background: To evaluate survival beyond 10 years of patients included in the French randomized trialcomparing neoadjuvant chemotherapy (CT-S) versus surgery alone (S) (initial publication: Depierre et al, J Clin Oncol 2002;20:247-53). Methods: Preoperative chemotherapy consisted of two cycles of mitomycin (6 mg/m2, day 1), ifosfamide (1.5 g/m2, days 1 to 3) and cisplatin (30 mg/m2, days 1 to 3), and two additional postoperative cycles for responding patients. Follow-up of patients by CT scan and fiberoptic bronchoscopy was scheduled for 7 years. Annual follow-up was performed thereafter and procedures were left to the investigator's discretion. Results: Three-hundred fifty-five eligible patients were randomized. Median follow-up was 13.8 years. The 10-year survival rate was 20.8% for the S arm and 29.4% for the CT-S arm (p=0.12). Multivariate analysis showed that neoadjuvant chemotherapy (HR=0.78; 95%CI= 0.61-0.99; p= 0.038), age, and the T and N status were significantly correlated with overall survival. The 10- year recurrence-free survival rate was 38.2% in the S arm and 54.6% in the CT-S arm (p = 0.001). The frequency of non-cancer deaths was identical in the 2 arms. The mortality rate from second primary cancer did not differ (6.9% in the S arm and 5% in the CT-S arm). At exploratory subgroup analyses, the 10- year survival rate for patients with stage I and II disease was 23.1% in the S arm and 37.6% in the CT-S arm (p = 0.04). The survival difference for patients with stage IIIa disease was not significant. Chemotherapy significantly increased survival in case of lobectomy (p=0.04) but not in case of a pneumonectomy. Conclusions: Neoadjuvant chemotherapy did not significantly increase long-term survival by univariate analysis. However, a 8% survival benefit in favor of neoadjuvant chemotherapy remained stable beyond 10 years and the multivariate analysis suggested a long-term benefit of neoadjuvant chemotherapy. No significant financial relationships to disclose.