tbuckley/cabot-search huggingface dataset:
Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected pulmonary metastases from colorectal cancer.
Authors: Nedim Turan, Faysal Dane, Olcun Umit Unal, Mustafa Benekli, Hasan volkan Kara, Dogan Koca, Ozlem Balvan, Tulay Eren, Didem Tastekin, Erkan Dogan, Kaan Helvaci, Umut Demirci, Veli Berk, Selcuk Cemil Ozturk, Mehmet Kucukoner, Mahmut Gumus, Ilhan Oztop, Ugur Coskun, Ahmet Ozet, Suleyman Buyukberber
Journal: Journal of Clinical Oncology (2013)

e14533 Background: To determine impact of modern chemotherapy regimens after pulmonary metastasectomy from colorectal cancer (CRC). Methods: A total of 122 consecutive patients who curatively resected for pulmonary metastases of CRC in eleven oncology centers were retrospectively analysed between January 2000 and April 2012. Results: Of 122 patients, 108 who received chemotherapy with fluoropyrimidine-based (n = 12), irinotecan-based (n = 56) and oxaliplatin-based (n = 40) combinations were analyzed. Among these, 52 patients received bevacizumab (BEV) while 56 did not (NoBEV). With a median follow-up of 14 months after metastasectomy, median recurrence-free survival (RFS) was 17 months, overall survival (OS) was not reached. Three and 5-years OS rates were 66% and 53%, respectively. There was no significant difference among cytotoxic regimens in respect to RFS and OS. Similarly, no significant difference was seen between BEV and NoBEV arms in respect to OS and RFS. In univariate analysis prior liver metastasectomy (p = 0.045), positive pulmonary margin (p = 0.028), disease-free interval &lt; 12 months (p = 0.013), and KRAS mutation (0.009) were negative significant prognostic for RFS. Thoracic pathological lymphatic involvement (p = 0.006) and higher prethoracotomy carcinoembryonic antigen (p = 0.038) were negative significant prognostic for OS. In multivariate analysis, positive pulmonary margin was the only negative independent prognostic for RFS, while thoracic lymphatic involvement was the only negative independent prognostic for OS. Conclusions: Chemotherapy type and addition of bevacizumab have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal pulmonary metastases.
Prognostic factors and survival in acral lentiginous melanoma
Authors: M.M. Asgari, L. Shen, M.M. Sokil, I. Yeh, E. Jorgenson
Journal: British Journal of Dermatology (2017)

Acral lentiginous melanoma (ALM) is a rare melanoma subtype that disproportionately afflicts people of colour. ALMs have a worse prognosis than other melanoma subtypes; this has been attributed to aggressive biological behaviour, more advanced stage at presentation and possible disparities in access to health care.To examine, using comprehensive patient data and long-term follow-up information in a well-characterized cohort, how patient, tumour and clinical management variables impact overall and melanoma-specific survival.We characterized a consecutive cohort of 123 ALMs diagnosed from 1987 to 2013 and analysed predictors of overall and melanoma-specific survival for their association with survival.Univariate hazard ratios and 95% confidence intervals using Cox regression models showed that increased Breslow depth, presence of ulceration, receipt of radiation, chemo- and vaccine therapy were associated with worse melanoma-specific survival. Notably, nonwhite race/ethnicity was not associated with worse overall or melanoma-specific survival. Multivariate modelling adjusting for patient, tumour and management variables revealed Breslow depth > 2 mm and disease extent as significantly associated with poor melanoma-specific survival.Melanoma-specific mortality among patients with ALM is associated with increased tumour thickness and more advanced stage at presentation, but not with race/ethnicity. Advanced tumour features at presentation and access to care may account for less favourable survival outcomes reported among nonwhite patients.
Inferring Allele Frequency Trajectories from Ancient DNA Indicates That Selection on a Chicken Gene Coincided with Changes in Medieval Husbandry Practices
Authors: Liisa Loog, Mark G. Thomas, Ross Barnett, Richard Allen, Naomi Sykes, Ptolemaios D. Paxinos, Ophélie Lebrasseur, Keith Dobney, Joris Peters, Andrea Manica, Greger Larson, Anders Eriksson
Journal: Molecular Biology and Evolution (2017)

Ancient DNA provides an opportunity to infer the drivers of natural selection by linking allele frequency changes to temporal shifts in environment or cultural practices. However, analyses have often been hampered by uneven sampling and uncertainties in sample dating, as well as being confounded by demographic processes. Here, we present a Bayesian statistical framework for quantifying the timing and strength of selection using ancient DNA that explicitly addresses these challenges. We applied this method to time series data for two loci: TSHR and BCDO2, both hypothesised to have undergone strong and recent selection in domestic chickens. The derived variant in TSHR, associated with reduced aggression to conspecifics and faster onset of egg laying, shows strong selection beginning around 1,100 years ago, coincident with archaeological evidence for intensified chicken production and documented changes in egg and chicken consumption. To our knowledge, this is the first example of preindustrial domesticate trait selection in response to a historically attested cultural shift in food preference. For BCDO2, we find support for selection, but demonstrate that the recent rise in allele frequency could also have been driven by gene flow from imported Asian chickens during more recent breed formations. Our findings highlight that traits found ubiquitously in modern domestic species may not necessarily have originated during the early stages of domestication. In addition, our results demonstrate the importance of precise estimation of allele frequency trajectories through time for understanding the drivers of selection.
Activation of NOTCH Signaling by Tenascin-C Promotes Growth of Human Brain Tumor-Initiating Cells
Authors: Susobhan Sarkar, Reza Mirzaei, Franz J. Zemp, Wu Wei, Donna L. Senger, Stephen M. Robbins, V. Wee Yong
Journal: Cancer Research (2017)

Oncogenic signaling by NOTCH is elevated in brain tumor-initiating cells (BTIC) in malignant glioma, but the mechanism of its activation is unknown. Here we provide evidence that tenascin-C (TNC), an extracellular matrix protein prominent in malignant glioma, increases NOTCH activity in BTIC to promote their growth. We demonstrate the proximal localization of TNC and BTIC in human glioblastoma specimens and in orthotopic murine xenografts of human BTIC implanted intracranially. In tissue culture, TNC was superior amongst several extracellular matrix proteins in enhancing the sphere-forming capacity of glioma patient-derived BTIC. Exogenously applied or autocrine TNC increased BTIC growth through an α2β1 integrin-mediated mechanism that elevated NOTCH ligand Jagged1 (JAG1). Microarray analyses and confirmatory PCR and Western analyses in BTIC determined that NOTCH signaling components including JAG1, ADAMTS15, and NICD1/2 were elevated in BITC after TNC exposure. Inhibition of γ-secretase and metalloproteinase proteolysis in the NOTCH pathway, or silencing of α2β1 integrin or JAG1, reduced the proliferative effect of TNC on BTIC. Collectively, our findings identified TNC as a pivotal initiator of elevated NOTCH signaling in BTIC and define the establishment of a TN-α2β1-JAG1-NOTCH signaling axis as a candidate therapeutic target in glioma patients. Cancer Res; 77(12); 3231-43. ©2017 AACR.
Capridine β (C-1748): A novel 1-nitroacridine derivative targets the cyclin dependent kinase, cdk4, and the tumor suppressor gene, p16 in prostate cancer.
Authors: Kiranmayi Tadi, Yuan-Gen Chen, Badithe T. Ashok, Venkata P. Garikapaty, Debabrata Banerjee, Barbara Wysocka-Skrzela, Jerzy Konopa, Raj K. Tiwari
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

3034 

Aromatase inhibitors (anastrozole, letrozole, and exemestane) are considered viable alternatives to tamoxifen for breast cancer therapy because they work by blocking the conversion of androgens to estrogen in post-menopausal women. Indeed, anastrozole has been shown to be superior to tamoxifen for the first-line treatment of postmenopausal women with advanced breast cancer, and letrozole is being investigated in several large adjuvant trials. However, there are concerns that like tamoxifen, patients who initially respond to aromatase inhibitors will eventually develop resistance. To address the issue of acquired resistance to aromatase inhibitors, we have developed a hormone-independent breast cancer cell line, MCF7:5C, which was originally cloned from the wild-type MCF7 cells [Jiang et al ., Mol. Cell. Endocrinol. 1992., 90(1):77-86]. Using DNA quantitation and trypan blue exclusion assays, we examined the effects of E2 and the antiestrogens 4-hydroxytamoxifen (4OHT), raloxifene, and fulvestrant on the growth of MCF7:5C cells. Our results showed that while E2 treatment (1 nM) stimulated the growth of parental MCF7 cells (∼10-fold above control), it caused a dramatic reduction in the growth of MCF7:5C cells with maximum inhibition (∼90%) at day 7. 4OHT, raloxifene, and fulvestrant (at 1 μM) also reduced the growth of MCF7:5C cells (55%, 62%, and 80%, respectively), however, their inhibitory effects were less than that of E2. To investigate whether the E2-induced growth inhibition of MCF7:5C cells was due to apoptosis, analyses were performed by Annexin V-FITC/Propidium iodide and DAPI staining and confirmed by electron microscopy. Flow cytometry analysis of MCF7:5C cells revealed that apoptotic cell population increased gradually from less than 5% in vehicle control to ∼70-80% with 1 nM E2, and that this effect was almost completely blocked by the universal capase inhibitor z-VAD-FMK and fulvestrant. Interestingly, we found that fulvestrant did not induce apoptosis in MCF7:5C cells despite its ability to significantly reduce the growth of these cell, thus suggesting an alternative mechanism for its growth inhibitory effects. Furthermore, western blot analyses revealed that E2 treatment significantly reduced the levels of the anti-apoptotic proteins Bcl-2, Bcl-xl, and Hsp27 but significantly increased the levels of Bax, Bid, and Bak (pro-apoptotic). Overall, these results show that E2 is capable of inducing apoptosis in long-term estrogen-deprived breast cancer cells and that this effect is most likely capase dependent and ER-mediated. This research was supported by the DOD grant DAMD17-001-0386 and the signal transduction grant T32CA70085.
‘New to me’: changing patient understanding of psoriasis and identifying mechanisms of change. The Pso Well<sup>®</sup>patient materials mixed‐methods feasibility study
Authors: P.A. Nelson, K. Kane, C.J. Pearce, C. Bundy, A. Chisholm, R. Hilton, R. Thorneloe, H. Young, C.E.M. Griffiths, L. Cordingley
Journal: British Journal of Dermatology (2017)

Psoriasis is an inflammatory long-term condition involving comorbidities, unhealthy lifestyle and significant life impact. Patients' understanding of psoriasis is limited and support lacking. The Common-Sense Model of Self-Regulation of Health and Illness emphasizes the role of illness and treatment beliefs on coping and self-management. New 'Pso Well® ' patient materials informed by the model, addressed psoriasis as a long-term condition, medication management and lifestyle behaviours.To investigate whether Pso Well® materials (i) broaden understanding of psoriasis without increasing anxiety; (ii) are acceptable; and (iii) comprise features that appear to effect change.The Revised Illness Perceptions Questionnaire (IPQ-R modified) and the Hospital Anxiety and Depression Scale (HADS) were administered in patients before and after intervention. Numerical rating scales assessed perceptions of change in understanding and anxiety resulting from engagement with the materials. Qualitative interviews explored acceptability and perceived 'active ingredients'.Fifty-five patients completed pre- and postintervention questionnaires (56% female; median age 59 years). Postintervention, a large effect size was indicated in two IPQ-R domains - illness coherence [t(55) = -3·48, P = 0·001 (two-tailed), η2 = 0·19] and personal control [t(55) = -2·98, P = 0·004 (two-tailed), η2 = 0·14] - and a medium effect in one, treatment control [t(55) = -2·08, P = 0·042 (two-tailed), η2 = 0·08]. HADS scores did not change. For numerical rating scales, 80% of participants reported increased understanding of psoriasis and none reported increased anxiety. Interviews with 19 patients indicated the materials were acceptable and usable. Factors reported to broaden understanding and promote engagement with self-management included linking of related disease aspects, personally relevant content and high-quality design.High-quality, theory-based psoriasis materials are acceptable to patients and can improve understanding and sense of control without increasing anxiety.
Hospital Admissions for Myocardial Infarction and Stroke Before and After the Trans-Fatty Acid Restrictions in New York
Authors: Eric J. Brandt, Rebecca Myerson, Marcelo Coca Perraillon, Tamar S. Polonsky
Journal: JAMA Cardiology (2017)

<h3>Importance</h3> Trans-fatty acids (TFAs) have deleterious cardiovascular effects. Restrictions on their use were initiated in 11 New York State (NYS) counties between 2007 and 2011. The US Food and Drug Administration plans a nationwide restriction in 2018. Public health implications of TFA restrictions are not well understood. <h3>Objective</h3> To determine whether TFA restrictions in NYS counties were associated with fewer hospital admissions for myocardial infarction (MI) and stroke compared with NYS counties without restrictions. <h3>Design, Setting, and Participants</h3> We conducted a retrospective observational pre-post study of residents in counties with TFA restrictions vs counties without restrictions from 2002 to 2013 using NYS Department of Health’s Statewide Planning and Research Cooperative System and census population estimates. In this natural experiment, we included those residents who were hospitalized for MI or stroke. The data analysis was conducted from December 2014 through July 2016. <h3>Exposure</h3> Residing in a county where TFAs were restricted. <h3>Main Outcomes and Measures</h3> The primary outcome was a composite of MI and stroke events based on primary discharge diagnostic codes from hospital admissions in NYS. Admission rates were calculated by year, age, sex, and county of residence. A difference-in-differences regression design was used to compare admission rates in populations with and without TFA restrictions. Restrictions were only implemented in highly urban counties, based on US Department of Agriculture Economic Research Service Urban Influence Codes. Nonrestriction counties of similar urbanicity were chosen to make a comparison population. Temporal trends and county characteristics were accounted for using fixed effects by county and year, as well as linear time trends by county. We adjusted for age, sex, and commuting between restriction and nonrestriction counties. <h3>Results</h3> In 2006, the year before the first restrictions were implemented, there were 8.4 million adults (53.6% female) in highly urban counties with TFA restrictions and 3.3 million adults (52.3% female) in highly urban counties without restrictions. Twenty-five counties were included in the nonrestriction population and 11 in the restriction population. Three or more years after restriction implementation, the population with TFA restrictions experienced significant additional decline beyond temporal trends in MI and stroke events combined (−6.2%; 95% CI, −9.2% to −3.2%;<i>P</i> &lt; .001) and MI (−7.8%; 95% CI, −12.7% to −2.8%;<i>P</i> = .002) and a nonsignificant decline in stroke (−3.6%; 95% CI, −7.6% to 0.4%;<i>P</i> = .08) compared with the nonrestriction populations. <h3>Conclusions and Relevance</h3> The NYS populations with TFA restrictions experienced fewer cardiovascular events, beyond temporal trends, compared with those without restrictions.
<i>In Vivo</i> Detection of EGFRvIII in Glioblastoma via Perfusion Magnetic Resonance Imaging Signature Consistent with Deep Peritumoral Infiltration: The <i>ϕ</i>-Index
Authors: Spyridon Bakas, Hamed Akbari, Jared Pisapia, Maria Martinez-Lage, Martin Rozycki, Saima Rathore, Nadia Dahmane, Donald M. O'Rourke, Christos Davatzikos
Journal: Clinical Cancer Research (2017)

Purpose: The epidermal growth factor receptor variant III (EGFRvIII) mutation has been considered a driver mutation and therapeutic target in glioblastoma, the most common and aggressive brain cancer. Currently, detecting EGFRvIII requires postoperative tissue analyses, which are ex vivo and unable to capture the tumor's spatial heterogeneity. Considering the increasing evidence of in vivo imaging signatures capturing molecular characteristics of cancer, this study aims to detect EGFRvIII in primary glioblastoma noninvasively, using routine clinically acquired imaging.Experimental Design: We found peritumoral infiltration and vascularization patterns being related to EGFRvIII status. We therefore constructed a quantitative within-patient peritumoral heterogeneity index (PHI/φ-index), by contrasting perfusion patterns of immediate and distant peritumoral edema. Application of φ-index in preoperative perfusion scans of independent discovery (n = 64) and validation (n = 78) cohorts, revealed the generalizability of this EGFRvIII imaging signature.Results: Analysis in both cohorts demonstrated that the obtained signature is highly accurate (89.92%), specific (92.35%), and sensitive (83.77%), with significantly distinctive ability (P = 4.0033 × 10-10, AUC = 0.8869). Findings indicated a highly infiltrative-migratory phenotype for EGFRvIII+ tumors, which displayed similar perfusion patterns throughout peritumoral edema. Contrarily, EGFRvIII- tumors displayed perfusion dynamics consistent with peritumorally confined vascularization, suggesting potential benefit from extensive peritumoral resection/radiation.Conclusions: This EGFRvIII signature is potentially suitable for clinical translation, since obtained from analysis of clinically acquired images. Use of within-patient heterogeneity measures, rather than population-based associations, renders φ-index potentially resistant to inter-scanner variations. Overall, our findings enable noninvasive evaluation of EGFRvIII for patient selection for targeted therapy, stratification into clinical trials, personalized treatment planning, and potentially treatment-response evaluation. Clin Cancer Res; 23(16); 4724-34. ©2017 AACR.
TCTAP C-201 A Case Complicated with Intravascular Ultrasound Catheter Entrapment After Coronary Artery Stenting
Authors: Takuya Tsujimura, Takayuki Ishihara, Osamu Iida, Shin Okamoto, Kiyonori Nanto, Shota Okuno, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2017)
Spatial heterogeneity in medulloblastoma
Authors: A Sorana Morrissy, Florence M G Cavalli, Marc Remke, Vijay Ramaswamy, David J H Shih, Borja L Holgado, Hamza Farooq, Laura K Donovan, Livia Garzia, Sameer Agnihotri, Erin N Kiehna, Eloi Mercier, Chelsea Mayoh, Simon Papillon-Cavanagh, Hamid Nikbakht, Tenzin Gayden, Jonathon Torchia, Daniel Picard, Diana M Merino, Maria Vladoiu, Betty Luu, Xiaochong Wu, Craig Daniels, Stuart Horswell, Yuan Yao Thompson, Volker Hovestadt, Paul A Northcott, David T W Jones, John Peacock, Xin Wang, Stephen C Mack, Jüri Reimand, Steffen Albrecht, Adam M Fontebasso, Nina Thiessen, Yisu Li, Jacqueline E Schein, Darlene Lee, Rebecca Carlsen, Michael Mayo, Kane Tse, Angela Tam, Noreen Dhalla, Adrian Ally, Eric Chuah, Young Cheng, Patrick Plettner, Haiyan I Li, Richard D Corbett, Tina Wong, William Long, James Loukides, Pawel Buczkowicz, Cynthia E Hawkins, Uri Tabori, Brian R Rood, John S Myseros, Roger J Packer, Andrey Korshunov, Peter Lichter, Marcel Kool, Stefan M Pfister, Ulrich Schüller, Peter Dirks, Annie Huang, Eric Bouffet, James T Rutka, Gary D Bader, Charles Swanton, Yusanne Ma, Richard A Moore, Andrew J Mungall, Jacek Majewski, Steven J M Jones, Sunit Das, David Malkin, Nada Jabado, Marco A Marra, Michael D Taylor
Journal: Nature Genetics (2017)
Intratumoral heterogeneity: pathways to treatment resistance and relapse in human glioblastoma
Authors: M.A. Qazi, P. Vora, C. Venugopal, S.S. Sidhu, J. Moffat, C. Swanton, S.K. Singh
Journal: Annals of Oncology (2017)

Intratumoral heterogeneity (ITH) has increasingly being described for multiple cancers as the root cause of therapy resistance. Recent studies have started to explore the scope of ITH in glioblastoma (GBM), a highly aggressive and fatal form of brain tumor, to explain its inevitable therapy resistance and disease relapse. In this review, we detail the emerging data that explores the extensive genetic, cellular and functional ITH present in GBM. We discuss current experimental models of human GBM recurrence and suggest harnessing new technologies (CRISPR-Cas9 screening, CyTOF, cellular barcoding, single cell analysis) to delineate GBM ITH and identify treatment-refractory cell populations, thus opening new therapeutic windows. We will also explore why current therapeutics have failed in clinical trials and how ITH can inform us on developing empiric therapies for the treatment of recurrent GBM.
Zoledronic Acid Dosing Interval for Metastatic Cancer
Authors: Tetsuya Tanimoto, Kenji Tsuda, Jinichi Mori
Journal: JAMA (2017)

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