tbuckley/cabot-search huggingface dataset:
Abstract 902: RNA-Seq profiling of silibinin effects on bladder cancer cells
Authors: Soichiro Yamamura, Yozo Mitsui, Nathan Bucay, Sharanjot Saini, Shahana Majid, Guoren Deng, Varahram Shahryary, Rajvir Dahiya, Yuichiro Tanaka
Journal: Cancer Research (2015)

Abstract Silibinin is the major active constituent of silymarin, an extract of the milk thistle seeds, containing a mixture of flavonolignans such as silibinin and isosilibinin. Silibinin has been shown to have significant anti-cancer effects in a variety of cancer types, including bladder, kidney, prostate, skin, breast, lung and colon cancer. Silibinin (10 μM) significantly suppressed proliferation and invasion of T24 and UM-UC-3 bladder cancer cells. Western blot analysis showed that silibinin significantly reduces expression of vimentin and slug in these bladder cells. Vimentin is overexpressed in various cancers and is known to promote tumor growth, invasion, and poor prognosis. Slug, a transcriptional repressor which mediates epithelial to mesenchymal transition (EMT), has been implicated in tumor metastasis. These results indicate that silibinin inhibits proliferation and invasion by suppressing vimentin and slug in bladder cancer cells. We studed the anti-cancer effects of silibinin in bladder cancer cells using RNA-Seq, a transcriptome profiling technique that uses deep-sequencing to quantitatively investigate the global behavior of transcriptomes. We will discuss the RNA-Seq profiling of the anti-cancer effects of silibinin in bladder cancer cells, including the vimentin and slug networks. Citation Format: Soichiro Yamamura, Yozo Mitsui, Nathan Bucay, Sharanjot Saini, Shahana Majid, Guoren Deng, Varahram Shahryary, Rajvir Dahiya, Yuichiro Tanaka. RNA-Seq profiling of silibinin effects on bladder cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 902. doi:10.1158/1538-7445.AM2015-902
Contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers and other high-risk women in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)
Authors: B. E. Kiely, M. A. Jenkins, J. M. McKinley, M. L. Friedlander, P. C. Weideman, R. Milne, S. McLachlan, J. L. Hopper, K. Phillips
Journal: Journal of Clinical Oncology (2009)

1509 Background: Contralateral risk-reducing mastectomy (CRRM) reduces contralateral breast cancer (BC) risk by up to 97%. Few studies have examined the prevalence and predictors of CRRM in BC patients at high familial risk of a second primary BC. Methods: Participants were women with unilateral BC and a strong family history of the disease, including BRCA1 and BRCA2 mutation carriers. Data were collected by interview, self-administered questionnaire, and review of pathology and surgical reports. Associations between having CRRM and potential predictors were assessed using multivariate logistic regression. Results: Of 1018 study participants (median follow-up 5.5 years), 154 (15%) underwent CRRM. The median time from initial BC to CRRM was 1 year. More likely to undergo CRRM were women who were younger at the time of their BC diagnosis (odds ratio [OR] = 0.94 per year of age, p &lt; 0.001), those diagnosed more recently (OR = 1.16 per calendar year, p &lt; 0.001), those who underwent mastectomy rather than breast conservation as their initial definitive BC treatment (OR = 5.2, p &lt; 0.001) and those who underwent risk-reducing salpingo-oophorectomy (OR = 3.4, p &lt; 0.001). BRCA1/2 mutation status and tumor characteristics were not independently associated with CRRM uptake. A contralateral BC event occurred in 177 (20.5%) of the 864 women who did not have CRRM, compared with one chest wall event (0.6%) in the 154 women post-CRRM. Conclusions: Younger women with more recently diagnosed BC treated with mastectomy were most likely to elect CRRM. BRCA1/2 mutation status and the competing risk of BC recurrence and death did not appear to influence decision making. No significant financial relationships to disclose.
An Intact Retroviral Gene Conserved in Spiny-Rayed Fishes for over 100 My
Authors: Jamie E. Henzy, Robert J. Gifford, Christopher P. Kenaley, Welkin E. Johnson
Journal: Molecular Biology and Evolution (2016)

We have identified a retroviral envelope gene with a complete, intact open reading frame (ORF) in 20 species of spiny-rayed fishes (Acanthomorpha). The taxonomic distribution of the gene, "percomORF", indicates insertion into the ancestral lineage >110 Ma, making it the oldest known conserved gene of viral origin in a vertebrate genome. Underscoring its ancient provenence, percomORF exists as an isolated ORF within the intron of a widely conserved host gene, with no discernible proviral sequence nearby. Despite its remarkable age, percomORF retains canonical features of a retroviral glycoprotein, and tests for selection strongly suggest cooption for a host function. Retroviral envelope genes have been coopted for a role in placentogenesis by numerous lineages of mammals, including eutherians and marsupials, representing a variety of placental structures. Therefore percomORF's presence within the group Percomorpha—unique among spiny-finned fishes in having evolved placentation and live birth—is especially intriguing.
Long-term survival in patients with HER2-positive metastatic breast cancer treated with trastuzumab as first-line therapy: Seven-year follow-up of the French Observational Hermine Study.
Authors: E. Antoine, F. Dalenc, C. Hebert, P. Rivera, G. Romieu, N. Varoqueaux, J. P. Guastalla, M. Namer
Journal: Journal of Clinical Oncology (2011)

617 Background: The Hermine study observed the use of trastuzumab (TZ) in HER2-positive metastatic breast cancer (MBC) in routine practice (in first (1st)-, second-, or third-line and beyond in 220, 138, and 243 patients, respectively), including patients who received TZ beyond progression (TBP). The 2-year OS estimate was 58% for 1st line patients. Because of the short follow-up (FUP) duration, few data exist on long-term survival of patients treated with TZ in this setting. Methods: The primary objective of our study was to describe and update the overall survival (OS) in HER2-positive MBC patients included in the Hermine study, 7 years after the start of TZ as 1st line therapy. All analyses were interpreted using the two-sided 5% level of significance. OS and Progression Free Survival (PFS) were estimated using the Kaplan-Meier method and comparisons using the log-rank test were performed according to the TZ continuation or not after the first progressive disease (PD). First PD sites (central nervous system and/or extra-cranial) were described when available. Results: Among the 102 patients alive at the end of the Hermine study (March 2005), data of 69 (67.6%) patients were collected retrospectively in 31 French sites (33 patients were lost to FUP). The estimated 7-year OS rate of the 220 patients treated with TZ as 1st line therapy was 17%, with a median OS of 2.5 years [95% CI 2.0;3.0]. Patients who continued to receive TZ (N=96) had an OS rate of 12.3% vs 5.4% (p< 0.0001) for patients who discontinued TZ (N=77), the median OS was 3.1 vs 1.45 years respectively. Median treatment duration was 1.2 years (0.0 to 8.7 years). The estimated 7-year PFS rate was 7.8%, with a median time to progression of 10.2 months [95% CI 9.1;12.4]. Among patients who progressed (n=57/69), the majority (85.2%) had extra-cranial first PD sites. Conclusions: Treatment with TZ in routine practice provided a substantial long-term survival benefit in HER2-positive MBC patients. This study adds to the evidence that there may be benefit in continuing TBP. Additionnal studies are needed to understand the clinical and tumor characteristics of long-term survivors and/or responders to TZ.
Hormonal impact of salvage chemotherapy with carboplatin plus weekly docetaxel in patients with castration- and docetaxel-resistant prostate cancer (DRPC).
Authors: Christoph W. Reuter, Michael A. Morgan, Martin Fenner, Philipp Ivanyi, Viktor Grünwald, Arnold Ganser
Journal: Journal of Clinical Oncology (2012)

e15190 Background: Recent data suggest that carboplatin may be effective in combination with docetaxel in DRPC. Platinum(II)-complexes interfere with steroid biosynthesis lowering testosterone levels by inhibiting CYP11A1, HSD3B1,2 and CYP17A1. Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2007) criteria. Since February 2005, 68 consecutive DRPC pts were treated with at least two cycles of carboplatin (C) AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel (D) at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG recommendations. Free testosterone levels were measured before (n=42) and during DC chemotherapy (n=36). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 32/68 (47.1%) patients. At the time of the current analysis (9/30/11) the median follow-up time was 13.6 months, 42/68 patients had died and 48/68 had progressive disease. Median progression-free survival (PFS) for all patients was 7.5 months (CI 95% 5.4, 9.6) and median overall survival (OS) was 18.6 months (CI 95% 11.7, 25.5). This regimen was reasonably well tolerated, with leukopenia/neutropenia as the most common reversible grade 3/4 toxicity (45.6/39.7%). Median free testosterone levels were 0.935 pg/ml before and 0.185 pg/ml during DC treatment (nadir levels, p&lt;0.001; detection limit &lt;0.18 pg/ml). Median serum androgene levels (T+DHT) were 0.26 ng/ml before and below the detection limit of &lt;0.05 ng/ml during DC treatment (median nadir levels). While free testosterone levels before DC treatment were associated with lower PSAR (HR 6.32 CI 1.60, 25,0; p=0.009), free testosterone nadir levels &lt;0.18 pg/ml during DC treatment were associated with higher PFS (HR 0.126 CI 0.04, 0.46, p=0.002) and OS (HR 0.07 CI 0.01, 0.59; p=0.014). Conclusions: These data suggest that carboplatin plus weekly docetaxel may be an important second-line treatment option for DRPC patients by inhibiting the testosterone biosynthesis.
PO58RE-DO SURGERY IN PATIENTS WITH GLIOBLASTOMA MULTIFORME - 8 YEARS OF EXPERIENCE FROM A SINGLE CENTRE
Authors: Anthony Wiggins, Paul Brennan, Imran Liaquat
Journal: Neuro-Oncology (2015)

INTRODUCTION: There remains debate on whether patients with recurrence of glioblastoma multiforme (GBM) should undergo further debulking surgery.Here we present the outcomes for all patients that underwent re-do surgery in a single centre as part of preparations for a randomised trial to investigate the benefits of re-do surgery for GBM.METHOD: Case notes for all patients with a diagnosis of GBM that had more than one debulking operation were reviewed from the last 8 years.RESULTS: 29 patients had a total of 2 debulking procedures and 2 patients had 3 debulking procedures.Excluding 3 patients still alive at the time of this review, median duration of survival from diagnosis was 530 days, and median duration of survival after re-do surgery was 193 days.The median interval between first and second procedures was 345 days.The median age at diagnosis was 52, and the average Karnofsky Performance Status at time of first surgery was 94%, which dropped to 80% prior to re-do surgery.3 patients (9.6%) developed wound infections after re-do surgery, and 4 patients (12.9%) developed new neurological deficits.Duration of survival after re-do surgery was increased in patients that had Gliadel w wafers placed at the time of re-do surgery from a median of 218 days compared to 165 days in patients where Gliadel w was not used.MGMT methylation status was available for 10 patients who had been operated on since 2012.Patients who were methylated had a median survival of 274 days after re-do surgery (excluding one person who was still alive), compared with 167 days for those who were un-methylated.CONCLUSION: Our single centre experience supports existing data on outcomes following re-do surgery for GBM.
Abstract 5183: Identification and characterization of wild type kinases driving prostate cancer metastasis
Authors: Claire Faltermeier, Justin Drake, Peter Clark, Bryan Smith, Colleen Mathis, Yang Zong, Carmen Volpe, Owen Witte
Journal: Cancer Research (2015)

Abstract Despite numerous oncogenic alterations implicated in metastatic prostate cancer, mutations or DNA amplifications of kinases are rare. We previously demonstrated that 1) expression of wild type (wt) Src in combination with the androgen receptor synergizes to produce aggressive prostate adenocarcinoma, 2) tyrosine phosphorylation increases with prostate cancer stage, and 3) the phosphoproteomic profile of metastatic prostate cancer is different from localized disease. However, the question still remains as to whether wt kinases can drive prostate cancer metastasis and should be regarded as therapeutic targets. To identify wt kinases driving prostate cancer metastasis, we performed phospho-tyrosine, threonine and serine peptide enrichment and quantitative mass spectrometry on metastatic prostate cancer tissues obtained at rapid autopsy. Analysis of this phosphoproteomic dataset combined with bioinformatic analyses of genomic datasets identified ∼140 kinases differentially expressed or activated in prostate cancer metastases. To determine which of these kinases function to promote prostate cancer metastasis, we developed an in vitro and in vivo metastasis screen. Out of 140 kinases, 20 kinases promote resistance to anoikis in vitro and metastatic colonization in vivo. Positive kinases include Src, Lyn, and EGFR which have been previously reported to be important in prostate cancer metastasis and thus provide strength to the validity of our screen. In addition we identified kinases with uncharacterized roles in prostate cancer metastasis and of particular interest, several of these kinases promote bone metastasis. We expect our findings will improve our understanding of the mechanistic role of kinase activation in prostate cancer and identify promising new therapeutic targets for metastatic disease. Citation Format: Claire Faltermeier, Justin Drake, Peter Clark, Bryan Smith, Colleen Mathis, Yang Zong, Carmen Volpe, Owen Witte. Identification and characterization of wild type kinases driving prostate cancer metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5183. doi:10.1158/1538-7445.AM2015-5183
A case for the therapeutic use of perfluorocarbon in pulmonary atelectasis
Authors: Shreya Bali, Gareth Morgan, Andrew Nyman, Simona Turcu, Andrew Durward
Journal: Thorax (2016)

SB: What is the advantage of PFC over the more conventional radiocontrast agents, such as Omnipaque?AD: PFC is inert and does not cause airway irritation and has high gas-carrying capabilities like conventional radiocontrast agents.Furthermore, it does not have the risk of causing anaphylactic reaction or impact on renal function, because its systemic absorption from the alveoli is limited.Furthermore, because of its oxygen-carrying capacity, it served two functions in our patient: ventilation and visualisation of the blocked areas of the left lung.SB: The last X-ray still shows a patchy distribution of PFC, how will this be resolved?AD: This will evaporate with time as the patient's ventilation gradually improves over time and she has better aeration of the left lung.PFC is relatively inert and, over the long term, may be taken up by macrophages and removed. 4
Abstract 4375: Podoplanin (PDPN): novel biomarker and chemotherapeutic target
Authors: Harini Krishnan, Jhon Ochoa-alvarez, Yongquan Shen, Evan Nevel, David Kephart, Angels Nguyen, Min Han, Nimish Acharya, Robert Nagele, Maria Ramirez, W. Todd Miller, Evelyne Kalyoussef, Soly Baredes, Mahnaz Fatahzadeh, Lasse Jensen, Alan Shienbaum, Gary Goldberg
Journal: Cancer Research (2015)

Abstract Cancer is a leading cause of death. In fact, cancer killed over 8 million people around the world in 2012. Over 90% of these cancer deaths are due to metastasis, which results from tumor cell migration and invasion. Specific cancer biomarkers need to be identified in order to effectively target these motile cells. The transmembrane glycoprotein receptor podoplanin (PDPN) promotes tumor cell motility and metastasis in many aggressive cancers. Indeed, PDPN has emerged as a prime cancer biomarker and chemotherapeutic target. Here, we describe how PDPN can be targeted to inhibit the growth and motility of melanoma and oral cancer cells. PDPN has a short intracellular domain of 9 amino acids which include two conserved serine residues. PDPN also has a large extracellular domain that is extensively O-glycosylated with α2,3-sialic acid linked to galactose. We are developing novel methods to target the intracellular and extracellular domains of PDPN to combat cancer progression. For example, we have found that some activators of protein kinase A can induce phosphorylation of the intracellular serine residues of PDPN to inhibit tumor cell migration. In addition, we have found that Maackia amurensis seed lectin (MASL) can target the extracellular domain of PDPN to inhibit tumor cell growth, migration, and tumor progression in cell culture and animal models. Furthermore, we utilized live cell imaging to find that PDPN expression can be modulated in cancer associated fibroblasts to inhibit neighboring tumor cell migration and survival. Thus, reagents can be used to target PDPN from inside of the cell and outside of the cell to inhibit tumor cell migration and combat cancer progression. This work illuminates novel strategies designed to exploit PDPN as a functionally relevant biomarker and chemotherapeutic target. Citation Format: Harini Krishnan, Jhon Ochoa-alvarez, Yongquan Shen, Evan Nevel, David Kephart, Angels Nguyen, Min Han, Nimish Acharya, Robert Nagele, Maria Ramirez, W. Todd Miller, Evelyne Kalyoussef, Soly Baredes, Mahnaz Fatahzadeh, Lasse Jensen, Alan Shienbaum, Gary Goldberg. Podoplanin (PDPN): novel biomarker and chemotherapeutic target. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4375. doi:10.1158/1538-7445.AM2015-4375
Phase 2 Trial of PRM-151, an Anti-Fibrotic Agent, in Patients with Myelofibrosis: Stage 1 Results
Authors: Srdan Verstovsek, Ruben A. Mesa, Lynda M Foltz, Vikas Gupta, John O Mascarenhas, Ellen K. Ritchie, Ronald Hoffman, Richard T. Silver, Marina Kremyanskaya, Olga Pozdnyakova, Robert P Hasserjian, Elizabeth Trehu, Hagop M. Kantarjian, Jason R. Gotlib
Journal: Blood (2014)
Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers
Authors: Avery DeVries, Gabriela Wlasiuk, Susan J. Miller, Anthony Bosco, Debra A. Stern, I. Carla Lohman, Janet Rothers, Anya C. Jones, Jessie Nicodemus-Johnson, Monica M. Vasquez, John A. Curtin, Angela Simpson, Adnan Custovic, Daniel J. Jackson, James E. Gern, Robert F. Lemanske, Stefano Guerra, Anne L. Wright, Carole Ober, Marilyn Halonen, Donata Vercelli
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract 4046: Interleukin-10 and programmed death-1 cooperate to regulate tumor antigen-specific CD8+ T cells in melanoma patients
Authors: Zhaojun Sun, Julien Fourcade, Ornella Pagliano, Joe-Marc Chauvin, Cindy Sander, John M. Kirkwood, Hassane M. Zarour
Journal: Cancer Research (2015)

Abstract With the recent success of immune checkpoint blockade in the clinic, it is expected that strategies aimed at counteracting the negative immunoregulatory networks in the tumor microenvironment will develop into potent therapy for melanoma. Here, we report that programmed death-1high (PD-1high) tumor antigen (TA)-specific CD8+ T cells present at periphery and at tumor sites in patients with advanced melanoma upregulate IL-10 receptor (IL-10R) expression. IL-10 is produced by multiple PBMC subsets in melanoma patients and acts directly on IL-10R+ TA-specific CD8+ T cells to impede proliferation and increase apoptosis. PD-1 blockade augments IL-10R expression by TA-specific CD8+ T cells, suggesting that PD-1 blockade renders PD-1+ TA-specific CD8+ T cells more sensitive to the immunosuppressive effects of endogenous IL-10. As a result, we show that IL-10 blockade adds to PD-1 blockade to increase the expansion and functions of TA-specific CD8+ T cells. Collectively, our findings support dual IL-10 and PD-1 blockade to counteract melanoma-induced T cell dysfunction and enhance TA-specific CD8+ T cell responses in patients with advanced melanoma. Citation Format: Zhaojun Sun, Julien Fourcade, Ornella Pagliano, Joe-Marc Chauvin, Cindy Sander, John M. Kirkwood, Hassane M. Zarour. Interleukin-10 and programmed death-1 cooperate to regulate tumor antigen-specific CD8+ T cells in melanoma patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4046. doi:10.1158/1538-7445.AM2015-4046
Improved Anemia, Organomegaly and Sustained Fetal Hemoglobin Induction within Aging TR2/TR4 Overexpressing UAB Sickle Cell Mice
Authors: Andrew Campbell, Kori Bradley, Ama Amachong, Jennifer Addo, Rebekah Urbonya, Kwaku Osei Bonsu, David Harro, David Giacherio, Lihong Shi, Shuaiying Cui, Osamu Tanabe
Journal: Blood (2012)
Pegilated Liposomal Doxorubicin in Combination with Cyclophosphamide, Vincristine, Prednisone and Rituximab in Patients with Newly Diagnosed Diffuse Large B Cell NHL: Clinical Efficacy and Related Cardiac Safety.
Authors: Leonardo Geraci, Mauro Colangelo, Roberto Ranalli, Serina Puglielli, Caterina Nenna, Franco Celeste
Journal: Blood (2006)