tbuckley/cabot-search huggingface dataset:
Safety of every 90 days portacath heparin maintenance flush in patients with cancer.
Authors: Eduardo Dias de Moraes, Leonardo Correia Santana, Angela Maria Costa Lessa, Ana Carolina Maciel, Gabriela Mesquita Dorea, Eulalia Cristina Leal de Oliveira Gonsalves, Aldo Lacerda Brasileiro, Gildete Sales Lessa
Journal: Journal of Clinical Oncology (2014)

e20654 Background: Totally implanted venous access devices, portacath, are widely used and improve the quality of life of patients in long term chemotherapy. It is recommended that they should be flushed every 4-6 weeks to keep patency, but no controlled clinical trial have been carried out to ascertain the best clinical practice. At NOB, portacath maintenance flushes are done every 90 days for the past 10 years, so as to coincide with patient’s routine follow-up visits. Methods: We evaluated, retrospectively, the medical records of 293 cancer patients with totally implanted venous access devices undergoing heparin maintenance flush every 90 days, for patency and rate of complications. We included patients with solid tumors that had completed adjuvant or neoadjuvant chemotherapy and patients in remission from hematologic cancer who underwent at least 2 cycles of every 90 days heparin maintenance flushes between November 1st, 2010 and May 30th, 2012. A cost saving analysis was performed comparing monthly maintenance heparin flushes versus those performed every 90 days. Results: Median patient age was 61 years. Two hundred twenty one patients (75,43%) were female and 72 (27,6%) were male. The majority of patients had solid tumors (77,1%) and 67 (22,9%) had hematologic cancers. During the study period, 29 patients (9,9%) had their portacath removed. Eighteen patients (5,25%) removed their catheters because they were no longer needed and 11 patients (3,75%) had their catheter removed due to catheter complications. Nine patients (3%) had catheter obstruction, 1 patient (0,3%) had catheter-related infection and 1 patient (0,3%) had a catheter rupture. Evaluation of the obstructed portacath showed that 5 patients had solid tumors (2,2% of all solid tumors) and 4 patients had hematologic cancer (6% of all hematologic cancers). Cost saving analysis showed that every 90 days heparin flush costs U$520.00/year and every 30 days costs U$1,560.00/year, representing savings of U$1,000,00/patient/year, not including patients’ transportation costs. Conclusions: Every 90 days portacath heparin maintenance flush is safe and cost-effective in patients with cancer.
PTU-001 Polyps at difficult and high risk location: video series to ilustrate the principles of assessment and resection: Abstract PTU-001 Table 1
Authors: AK Kurup, R Bhattacharyya, F Chedgy, K Kandiah, P Bhandari
Journal: Gut (2015)

<h3>Introduction</h3> One of the factors which make the removal of a polyp challenging is its location in the GI tract. We will present a series of video clips of polyps located in difficult locations to demonstrate the challenges facing the endoscopist and discuss the strategies to circumvent the problem. Three types of polyps are discussed in this abstract: 1. Polyps involving the dentate line 2. Polyps involving the ileo-caecal valve and terminal ileum and 3. Polyps involving the appendiceal orifice. <h3>Method</h3> Information regarding the nature, location, procedure, recurrence, complication and need for surgery was obtained from a prospective database of polyps more than 2 cm removed between 2010 and 2014. <h3>Results</h3> 1. Polyp involving the dentate line: Access to these polyps is very difficult. A rich sensory supply of the distal squamous epithelium, difficulty in identifying the distal edge of the polyp and the rich vascular supply in this region makes it challenging. Twelve cases [n = 12] underwent endoscopic resection. The size ranged from 12 mm–150 mm occupying 25% to 80% of the circumference. Laterally spreading tumour –Granular [n = 10] and two were sessile [1s and 1s/2c, n = 2]. 1. Polyp involving the ileo –caecal valve. Here the challenges include difficult access, identifying the margins, ileal extension and risk of perforation. Seven polyps, 30 mm–60 mm in size and involving the ileo- caecal valves were removed endoscopically. LST –G [5], 1s [1] and SSA [1]. 1. Polyp involving the appendicular orifice Decision to resect these polyps should be weighed against the risk of perforation since these polyps could extend into the appendicular canal. Nine cases of polyp involving the appendicular orifice were resected endoscopically with size ranging from 20 mm -100 mm. Six were LST –G[[7]sessile polyp [2]. Histology of the resected polyps was as follows. TVA with LGD [21], TVA with foci of HGD [2], sessile serrated adenoma [4], tubular adenoma with intra mucosal cancer [1], Tubular adenoma [1]. <h3>Conclusion</h3> Polyps located at the appendicular orifice and ileo -caecal valve have traditionally been managed with right hemicolectomy and polyps at the dentate line with TAR/TEMS. Our data shows that an expert endoscopist can resect these polyps with good clearance and avoid surgery. This makes a case for referral of these polyps to an expert centre. <h3>Disclosure of interest</h3> None Declared.
Diagnosis of Smith-Lemli-Opitz Syndrome
Authors: J McGaughran, D Donnai, P Clayton, K Mills
Journal: New England Journal of Medicine (1994)

An abnormality in cholesterol synthesis was described recently in the Smith-Lemli-Opitz (SLO) syndrome. Here we describe how the application of this finding has enabled an accurate prenatal diagnosis, We also discuss the possible use of this test in detecting heterozygotes.
Anti-inflammatory Agents in the Treatment of Diabetes and Its Vascular Complications
Authors: Rena M. Pollack, Marc Y. Donath, Derek LeRoith, Gil Leibowitz
Journal: Diabetes Care (2016)

The association between hyperglycemia and inflammation and vascular complications in diabetes is now well established. Antidiabetes drugs may alleviate inflammation by reducing hyperglycemia; however, the anti-inflammatory effects of these medications are inconsistent and it is unknown whether their beneficial metabolic effects are mediated via modulation of chronic inflammation. Recent data suggest that immunomodulatory treatments may have beneficial effects on glycemia, β-cell function, and insulin resistance. However, the mechanisms underlying their beneficial metabolic effects are not always clear, and there are concerns regarding the specificity, safety, and efficacy of immune-based therapies. Herein, we review the anti-inflammatory and metabolic effects of current antidiabetes drugs and of anti-inflammatory therapies that were studied in patients with type 2 diabetes. We discuss the potential benefit of using anti-inflammatory treatments in diabetes and important issues that should be addressed prior to implementation of such therapeutic approaches.
Maintenance vinflunine post cisplatin chemotherapy (CT) in patients with advanced urothelial carcinoma (UC): Preliminary analysis of a randomized placebo controlled phase II trial (MAJA trial)—SOGUG 2011-02.
Authors: Joaquim Bellmunt, Begona Perez Valderrama, Albert Font, Juan Antonio Virizuela, Miguel Angel Climent, Susana Hernando Polo, Begona Mellado, Nuria Laínez, Aranzazu Gonzalez del Alba, Jose Angel Arranz, Jose Carlos Villa Guzman, Maria del Mar LLorente, Daniel E. Castellano, Enrique Gallardo, Xavier Garcia del Muro, Urbano Anido, Montserrat Domenech, Javier Puente, Jose Luis Perez Gracia, Jesús García-Donas
Journal: Journal of Clinical Oncology (2015)

4529 Background: Vinflunine (VFL) is a microtubule inhibitor approved by EMA as treatment after platinum progression, in metastatic bladder cancer. We evaluated whether maintenance VFL delays progression after response to CT. Methods: Patients (pts) with measurable disease, locally recurrent/metastatic UC and adequate organ function with radiological response or stabilization after 4-6 cy of a cisplatin/gemcitabine chemotherapy (carboplatin allowed after cy 4) were randomized 1:1 to receive VFL 320 mg/m2 or 280mg/m2(in case of PS 1, age ≥ 75 years, prior pelvic radiotherapy or CrCl < 60ml/min) every 21 days vs best supportive care (BSC), until disease progression. The primary endpoint was progression free survival (PFS). With a median PFS considered unacceptable for the experimental arm 4 months (p0) and a very acceptable 6.5 (p1). 39 eligible pts per treatment arm were required to select better therapy with a type I error of 0.05 (α, one-tailed test), and a type II 0.1 (β) error. Results: 88 patients from 21 institutions of SOGUG cooperative group have been randomized between 04/2012 and 01/2015. At the time of present analysis 77 have confirmed eligibility and 66 pts (33 in the VFL arm and 33 in the BSC arm) have received at least 2 cy. Preliminary results based on these 66 pts are presented. Median age 63 years (range 42-78); PS 0/1, 50%/50%; CrCl < 60 ml/min 24%; liver metastasis 25%; prior pelvic RT 10%. Primary location: bladder 82%. Metastatic/locoregional disease 77%/23%. Pure transitional 87%. 242 cy given in the VFL arm with a median of 4 cycles per patient (1–28). Most common G 3/4 (% pts) AEs were constipation (17.6%), neutropenia (17.6%), fatigue (11.7%), and 1 febrile neutropenia (2.9%). 2 deaths due to pneumonia not related to the treatment. With a median follow-up of 7.2 months (0.1-29.9), the median PFS was 10.4 months (0-24.6) in the VFL arm and 4.6 months (1.7-7.4) in the BSC arm (p = 0.058). Conclusions: Preliminary results indicate that maintenance VFL post CT has an acceptable tolerability profile in advanced UC pts and is associated with clinical activity. Further follow-up with mature results are needed. Clinical trial information: NCT01529411.
Divergent Ah Receptor Ligand Selectivity during Hominin Evolution
Authors: Troy D. Hubbard, Iain A. Murray, William H. Bisson, Alexis P. Sullivan, Aswathy Sebastian, George H. Perry, Nina G. Jablonski, Gary H. Perdew
Journal: Molecular Biology and Evolution (2016)

We have identified a fixed nonsynonymous sequence difference between humans (Val381; derived variant) and Neandertals (Ala381; ancestral variant) in the ligand-binding domain of the aryl hydrocarbon receptor (AHR) gene. In an exome sequence analysis of four Neandertal and Denisovan individuals compared with nine modern humans, there are only 90 total nucleotide sites genome-wide for which archaic hominins are fixed for the ancestral nonsynonymous variant and the modern humans are fixed for the derived variant. Of those sites, only 27, including Val381 in the AHR, also have no reported variability in the human dbSNP database, further suggesting that this highly conserved functional variant is a rare event. Functional analysis of the amino acid variant Ala381 within the AHR carried by Neandertals and nonhuman primates indicate enhanced polycyclic aromatic hydrocarbon (PAH) binding, DNA binding capacity, and AHR mediated transcriptional activity compared with the human AHR. Also relative to human AHR, the Neandertal AHR exhibited 150–1000 times greater sensitivity to induction of Cyp1a1 and Cyp1b1 expression by PAHs (e.g., benzo(a)pyrene). The resulting CYP1A1/CYP1B1 enzymes are responsible for PAH first pass metabolism, which can result in the generation of toxic intermediates and perhaps AHR-associated toxicities. In contrast, the human AHR retains the ancestral sensitivity observed in primates to nontoxic endogenous AHR ligands (e.g., indole, indoxyl sulfate). Our findings reveal that a functionally significant change in the AHR occurred uniquely in humans, relative to other primates, that would attenuate the response to many environmental pollutants, including chemicals present in smoke from fire use during cooking.
Abstract 2756: SMARCAD1 depletion enhances hyperthermia-mediated radiosensitization by decreasing resection and enhancing stalled replication forks
Authors: Sharmistha Chakraborty, Clayton R. Hunt, Shashank Hambarde, Kalpana Mujoo, Nobuo Horikoshi, Raj K. Pandita, Abid Mattoo, Bin Teh, Tej K. Pandita
Journal: Cancer Research (2016)

Abstract Hyperthermia is the most effective chemo- and radio-sensitizer in use clinically for containing tumor growth. Hyperthermia is proposed to induce degradation of BRCA2, the protein involved in homologous recombination (HR) repair of DNA double strand breaks and, thus sensitizes cells to poly (ADP-ribose) polymerase (PARP)-1 inhibition. We and other laboratories have reported that hyperthermia inhibits DNA damage repair. Since HR includes single-strand annealing, gene conversion and break-induced replication, it is critical for DNA replication during recovery of stalled replication forks, but it is not yet clear how hyperthermia affects these important steps in HR. Here we report that SMARCAD1 depletion increases hyperthermia induced cell death and chromosome damage in irradiated S-phase cells. Combined SMARCAD1 depletion and hyperthermia treatment decreased repair and recruitment of repairosome proteins to ISce-1 induced DSBs as well as decreased IR-induced repairosome foci formation. This effect was limited to S-phase cells, where homologous recombination is up regulated and the predominant pathway of DSB repair. Hyperthermia decreased the quantity of 5′ single stranded DNA intermediates at endonuclease-generated DNA break sites, an effect that was further decreased by SMARCAD1 depletion. Consistent with these results, simultaneous SMARCAD1 depletion and hyperthermia increased replication fork stalling and affected firing of new replication origins. The results presented here support a mechanism by which SMARCAD1 depletion and hyperthermia mediate radiosensitization through inhibition of the DNA resection step that precedes strand homology search during HR repair of IR-induced DSBs. Citation Format: Sharmistha Chakraborty, Clayton R. Hunt, Shashank Hambarde, Kalpana Mujoo, Nobuo Horikoshi, Raj K. Pandita, Abid Mattoo, Bin Teh, Tej K. Pandita. SMARCAD1 depletion enhances hyperthermia-mediated radiosensitization by decreasing resection and enhancing stalled replication forks. [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 2756.
Cancer research must focus on how cancer cells evolve, new UK strategy argues
Authors: Susan Mayor
Journal: BMJ (2016)

Understanding how cancer cells evolve in individual patients is key to developing more effective treatment strategies to improve long term survival, the UK Institute of Cancer Research has argued in its research strategy for the next five years.

“Cancer evolution is the single biggest challenge we face in creating better treatments for patients,” said Paul Workman, chief executive of the institute, which is based in London.

“We have seen some great advances against cancer, but so often we find that the disease evolves, becoming ever more complex and genetically diverse, and finds ways to resist the effects of therapy,” he explained. “Cancer doesn’t stand still.”

To tackle this challenge, the …
Abstract 2530: Live cell detection of intracellular biomarkers maintains cancer stem cells for further experimentation
Authors: Don Weldon, Yuko Williams, Amish Patel, Steven McClellan
Journal: Cancer Research (2016)

Abstract Cancer stem cells are widely studied as a potential therapeutic target in cancer research. Their expression of cell surface biomarkers such as EpCAM, CD44, and CD133 have been well characterized as a method for identification and enrichment from heterogeneous populations. Additional biomarkers with more functional relevance to self-renewal such as the transcription factors Sox-2 and Nanog, are intracellular and traditionally require fixation and permeabilization of the sample. Here we describe a method for identification and enrichment of live cancer stem cells based on intracellular biomarker expression. Live human head and neck squamous cell carcinoma (HNSCC) cell lines, UM-SCC-47 and UM-SCC-104 were used as a model for Cancer stem cells in a mixed population. They were assayed for their expression of EpCAM, CD44, and CD133 by flow cytometry. Additionally, Aldehyde dehydrogenase (ALDH) activity was also detected in a population of the HNSCC cell lines further corroborating the presence of a cancer stem cell population. Live cell probes specific to Nanog and Sox-2 were used to enrich for cells expressing the targets of interest through Fluorescent Activated Cell Sorting (FACS). This live cell biomarker approach was also recently demonstrated on solid tumors which were digested and cultured as single cells where they were then incubated with the live cell probes. FACS sorting was utilized to enrich for a cancer stem cell population. More importantly after detection these cells remain live and intact allowing them to be returned to culture and further studied. Citation Format: Don Weldon, Yuko Williams, Amish Patel, Steven McClellan. Live cell detection of intracellular biomarkers maintains cancer stem cells for further experimentation. [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 2530.
ROLE OF APOLIPOPROTEIN-E (APOE) IN INTRACELLULAR LIPID-METABOLISM AND VERY-LOW-DENSITY LIPOPROTEIN (VLDL) SECRETION BY MOUSE HEPATOCYTES
Authors: Folkert Kuipers, Rick Havinga, Mh Hofker, Roelf Vonk, Hmg Princen, Lm Havekes
Journal: Hepatology (1995)
Histone deacetylase 3 regulates the inflammatory gene expression programme of rheumatoid arthritis fibroblast-like synoviocytes
Authors: Chiara Angiolilli, Pawel A Kabala, Aleksander M Grabiec, Iris M Van Baarsen, Bradley S Ferguson, Samuel García, Beatriz Malvar Fernandez, Timothy A McKinsey, Paul P Tak, Gianluca Fossati, Paolo Mascagni, Dominique L Baeten, Kris A Reedquist
Journal: Annals of the Rheumatic Diseases (2016)

Non-selective histone deacetylase (HDAC) inhibitors (HDACi) have demonstrated anti-inflammatory properties in both in vitro and in vivo models of rheumatoid arthritis (RA). Here, we investigated the potential contribution of specific class I and class IIb HDACs to inflammatory gene expression in RA fibroblast-like synoviocytes (FLS).RA FLS were incubated with pan-HDACi (ITF2357, givinostat) or selective HDAC1/2i, HDAC3/6i, HDAC6i and HDAC8i. Alternatively, FLS were transfected with HDAC3, HDAC6 or interferon (IFN)-α/β receptor alpha chain (IFNAR1) siRNA. mRNA expression of interleukin (IL)-1β-inducible genes was measured by quantitative PCR (qPCR) array and signalling pathway activation by immunoblotting and DNA-binding assays.HDAC3/6i, but not HDAC1/2i and HDAC8i, significantly suppressed the majority of IL-1β-inducible genes targeted by pan-HDACi in RA FLS. Silencing of HDAC3 expression reproduced the effects of HDAC3/6i on gene regulation, contrary to HDAC6-specific inhibition and HDAC6 silencing. Screening of the candidate signal transducers and activators of transcription (STAT)1 transcription factor revealed that HDAC3/6i abrogated STAT1 Tyr701 phosphorylation and DNA binding, but did not affect STAT1 acetylation. HDAC3 activity was required for type I IFN production and subsequent STAT1 activation in FLS. Suppression of type I IFN release by HDAC3/6i resulted in reduced expression of a subset of IFN-dependent genes, including the chemokines CXCL9 and CXCL11.Inhibition of HDAC3 in RA FLS largely recapitulates the effects of pan-HDACi in suppressing inflammatory gene expression, including type I IFN production in RA FLS. Our results identify HDAC3 as a potential therapeutic target in the treatment of RA and type I IFN-driven autoimmune diseases.
Case 59-1963
Authors: Edward F. Bland, Benjamin Castleman
Journal: New England Journal of Medicine (1963)

Presentation of Case First admission. A fifty-nine-year-old man entered the hospital because of dyspnea.Nine years before admission the patient became aware of gradually progressive dyspnea accompanied by aching in the forearms and calves; the symptoms appeared during walking and were relieved with rest. Two years later he was said to have congestive heart failure with a systolic murmur, and an electrocardiogram was interpreted as showing right ventricular strain and atrial enlargement; digitalis therapy was begun, but had little effect. During the seven years before entry he experienced pruritus after taking a bath. Shortly before admission he was informed . . .
Abstract 177: Src family kinase Fyn promotes the neuroendocrine phenotype and visceral metastasis in advanced prostate cancer
Authors: Karen Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael Freeman, Gina Chia-Yi Chu, Neil Bhowmick, Leland Chung, Edward Posadas
Journal: Cancer Research (2016)

Abstract FYN is a SRC family kinase (SFK) that has been shown to be up-regulated in human prostate cancer (PCa) tissues and cell lines. In this study, we observed that FYN is strongly up-regulated in human neuroendocrine PCa (NEPC) tissues and xenografts, as well as cells derived from a NEPC transgenic mouse model. In silico analysis of FYN expression in prostate cancer cell line databases revealed an association with the expression of neuroendocrine (NE) markers such as CHGA, CD44, CD56, and SYP. The loss of FYN abrogated the invasion of PC3 and ARCaPM cells in response to MET receptor ligand HGF. FYN also contributed to the metastatic potential of NEPC cells in two mouse models of visceral metastasis with two different cell lines (PC3 and TRAMPC2-RANKL). The activation of MET appeared to regulate neuroendocrine (NE) features as evidenced by increased expression of NE markers in PCa cells lines treated with HGF. Importantly, the overexpression of FYN protein in DU145 cells was directly correlated with the increase of CHGA. Thus, our data demonstrated that the neuroendocrine differentiation that occurs in PCa cells is, at least in part, regulated by FYN kinase. Understanding the role of FYN in the regulation of NE markers will provide further support for ongoing clinical trials of SFK and MET inhibitors in castration-resistant PCa patients. Citation Format: Karen Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael Freeman, Gina Chia-Yi Chu, Neil Bhowmick, Leland Chung, Edward Posadas. Src family kinase Fyn promotes the neuroendocrine phenotype and visceral metastasis in advanced prostate cancer. [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 177.
A third option in the management of patients with clinical stage I nonseminomatous germ cell tumor?
Authors: V H Gressler, L A Levine, N J Vogelzang
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.1.4 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2153195 A third option in the management of patients with clinical stage I nonseminomatous germ cell tumor? V H GresslerxV H GresslerSearch for articles by this author , L A LevinexL A LevineSearch for articles by this author , N J VogelzangxN J VogelzangSearch for articles by this author Show More University of Chicago, IL. https://doi.org/10.1200/JCO.1990.8.1.4 First Page PDF © 1990 by American Society of Clinical Oncology
Pseudocirrhosis and liver failure in patients with metastatic breast cancer after treatment with palbociclib
Authors: Raj Vuppalanchi, Romil Saxena, Anna Maria V. Storniolo, Naga Chalasani
Journal: Hepatology (2016)

Vuppalanchi, Raj; Saxena, Romil; Storniolo, Anna Maria V.; Chalasani, Naga Author Information