tbuckley/cabot-search huggingface dataset:
Effects of Anticancer Drugs on Chromosome Instability and New Clinical Implications for Tumor-Suppressing Therapies
Authors: Hee-Sheung Lee, Nicholas C.O. Lee, Natalay Kouprina, Jung-Hyun Kim, Alex Kagansky, Susan Bates, Jane B. Trepel, Yves Pommier, Dan Sackett, Vladimir Larionov
Journal: Cancer Research (2016)

Abstract Whole chromosomal instability (CIN), manifested as unequal chromosome distribution during cell division, is a distinguishing feature of most cancer types. CIN is generally considered to drive tumorigenesis, but a threshold level exists whereby further increases in CIN frequency in fact hinder tumor growth. While this attribute is appealing for therapeutic exploitation, drugs that increase CIN beyond this therapeutic threshold are currently limited. In our previous work, we developed a quantitative assay for measuring CIN based on the use of a nonessential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene. Here, we used this assay to rank 62 different anticancer drugs with respect to their effects on chromosome transmission fidelity. Drugs with various mechanisms of action, such as antimicrotubule activity, histone deacetylase inhibition, mitotic checkpoint inhibition, and targeting of DNA replication and damage responses, were included in the analysis. Ranking of the drugs based on their ability to induce HAC loss revealed that paclitaxel, gemcitabine, dactylolide, LMP400, talazoparib, olaparib, peloruside A, GW843682, VX-680, and cisplatin were the top 10 drugs demonstrating HAC loss at a high frequency. Therefore, identification of currently used compounds that greatly increase chromosome mis-segregation rates should expedite the development of new therapeutic strategies to target and leverage the CIN phenotype in cancer cells. Cancer Res; 76(4); 902–11. ©2016 AACR.
Development and validation of a prognostic index for allograft outcome in kidney recipients with transplant glomerulopathy
Authors: Pallavi Patri, Surya V. Seshan, Marie Matignon, Dominique Desvaux, John R. Lee, Jun Lee, Darshana M. Dadhania, David Serur, Philippe Grimbert, Choli Hartono, Thangamani Muthukumar
Journal: Kidney International (2015)
Interaction between glucocorticoids and estrogens in androgen independent prostate cancer - a randomised phase 2 study
Authors: J. Shamash, C. Barlow, E. Heath, P. Wilson, W. Ansell, U. Somasundram, R. Oliver, A. Protheroe
Journal: Journal of Clinical Oncology (2004)

4755 Background There has been considerable interest in the use of combinations of Taxanes and Estramustine to manage androgen independent prostate cancer. Some of the benefit may be due to the interaction between glucocorticoid used as premedication and the estrogenic activity of estramustine. TO assess this a randomised phase 2 study has been undertaken using Dexamethasone (D), known to be the most highly active glucocorticoid and immediate verses deferred stilbestrol (S). This abstracts reviews the outcome of a randomised phase 2 study done as a prelude to deciding whether a phase 3 study is justified. Methods 58 biochemically castrate patients with androgen independent prostate cancer and rising PSA and no absolute contra-indications to steroids or estrogens were randomised between daily D 2mg and Aspirin (A) 75mg +/- immediate S 1mg (DAS). Patients on DA received S on progression. On entry median age was 75(56–89), median PSA was 112(12–4590), 74% had bone metastases. Monthly quality of lfe assessments was made. Results 31 patients received DAS and 27 patients DA, and 20 on progression after DA received added stilbestrol. 17/31 (55% had at least a 50% response to DAS. 14/27 (51%) responded to DA. An additional 6 subsequently responded to S leading to a cumulative response rate of 74%. 12 patients on progression off study received chemotherapy, 2 had a 50% PSA response and following progression 2/5 had a further PSA response to retesting with LHRH. Overall actuarial survival at 12 months was 69% in DA arm (median 20.4 months) and 51% in DAS arm (median14.8 months) (p = 0.06). Conclusion Sequential DA + S rather than immediate synchronous DAS treatment may offer possible advantage though quality of life and larger numbers are required to confirm this observation. No significant financial relationships to disclose.
Recovery of Radioactivity of &lt;italic&gt;N,N&lt;/italic&gt;′-2,7-Fluorenylenebisacetamide-9-C&lt;sup&gt;14&lt;/sup&gt; From Rats
Authors: Helen M. Dyer, Kira K. Lueders, Harold P. Morris
Journal: JNCI Journal of the National Cancer Institute (1967)

N,N′-2,7-Fluorenylenebisacetamide (2,7-FAA) induces carcinomas and precancerous lesions of the glandular stomach in addition to cancers of other tissues of rats. When single doses of approximately 1 mg (7 × 106 cpm) 2,7-FAA-9-C14 were administered by the intra-peritoneal route or by stomach tube to male Buffalo rats, the distribution of total recoverable radioactivity in the urine (50–60%) and feces was similar, but excretion was more prolonged after intraperitoneal administration. In rats with bile fistula, the amount of radioactivity recovered from the bile was similar to that recovered from the feces of intact rats and the amount of radioactivity of the feces was correspondingly decreased. With a dose of 10 mg by stomach tube, 80–90% of the administered radioactivity was excreted in the feces within 48 hours. Autoradiographs of chromatographed ether extracts of urine revealed one major radioactive spot and a small amount of 2,7-FAA. Occasionally other minor spots indicated that there may have been several metabolites of 2,7-FAA in the rat but only one present in abundance. Alcohol extracts of feces after stomach tube administration contained a large amount of 2,7-FAA and a small amount of the “major” urinary metabolite, whereas the reverse was observed after intraperitoneal administration. Respiratory CO2 from a rat given 2,7-FAA-9-C14 by stomach tube contained no radioactivity, whereas radioactivity was excreted in the expired air of 2 rats given 2,7-FAA-1′-C14.
Age of Parents and Risk of Gestational Trophoblastic Disease&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C La Vecchia, F Parazzini, A Decarli, S Franceschi, M Fasoli, G Favalli, E Negri, S Pampallona
Journal: JNCI Journal of the National Cancer Institute (1984)

The relationship of gestational trophoblastic disease (GTD) to parental age was evaluated in a case-control study of 132 women with hydatidiform mole (108) or choriocarcinoma (24) and 304 control subjects hospitalized for normal deliveries. Cases and controls were recruited in Lombardy (Northern Italy), and all were white and Italian. Compared to the risk of developing trophoblastic tumors in women 21-35 years old, the risk of developing trophoblastic tumors was elevated both in younger [less than or equal to 20 yr old, relative risk (RR) = 1.4, with 95% confidence interval (Cl) of 0.7-2.8] and in older subjects, RR being 1.2 (95% Cl 0.7-2.8) and 5.2 (95% Cl 2.2-12.3) for women 36-40 years old and over 40, respectively. The risk estimates for the last two categories were reduced to 0.7 (with 95% Cl of 0.3-1.9) and 2.5 (with 95% Cl of 0.7-8.9) when adjustment was made for paternal age by means of the Mantel-Haenszel procedure. Higher paternal age also was associated with GTD: Women whose husbands were 41-45 years old and over 45 had RR of 1.6 (with 95% Cl = 0.7-3.7) and 4.9 (with 95% Cl = 2.2-11.1), respectively, compared to women married to men less than 40 years old. These risk estimates were practically unchanged when adjustment was made for the woman's age. Examination of the effects of parental and maternal ages suggests that the highest risk estimate was observed when both parents were older. The findings of the present study were consistent with increased risk in the youngest maternal age group and confirm that older maternal age is associated with increased risk of GTD. Furthermore, showing a strong, independent effect of paternal age, they give epidemiologic support to the cytogenetic evidence of an androgenetic role in the origin of GTD.
Genomic Characterization Of Histiocytic Lesions Following Pediatric T-Cell Acute Lymphoblastic Leukemia
Authors: Richard McMasters, Brian K. Turpin, Michael J. Absalon, Christine L. Phillips, Karen Burns, Christopher E. Dandoy, Nihal Bakeer, Jun Mo, John Perentesis, Maureen M. O'Brien
Journal: Blood (2013)
Within-breath femoral venous blood flow modulation
Authors: Barbara Uva, Dario Bovio, Edoardo Colombo, Andrea Aliverti
Journal: European Respiratory Journal (2012)

Breathing has a large effect on venous return and abdominal pressure (Pab) variations can cause the interruption of femoral venous flow (Qfv). The purpose of this study was to determine the values of Pab, airflow, volume and time at which Qfv ceases and restarts within the respiratory cycle time (T tot ).  In 4 healthy subjects (age 45±22.1 yr) lying in semirecumbent position airflow was measured during quiet breathing (QB) by a pneumotachograph, Pab by gastric pressure measurements using catheter-balloon-transducer system and Qfv by an echo-Doppler probe. Qfv contour was extracted from the images recorded by the echo-Doppler. The values of Pab, airflow, volume above FRC (ΔV) and times t 1  and t 2  at which Qfv stopped and restarted (where femoral venous velocity could no longer be detected and became measurable again) within T tot  were calculated (see figure for a representative case).  t 1  and t 2  occurred respectively during inspiration and expiration when airflow averaged 0.40±0.04 and -0.39±0.10 L/sec. No significant difference between Pab at t 1  (3.1±2.3 cmH 2 O) and t 2  (2.8±2.0 cmH 2 O) was found. ΔV was 0.33±0.09 at t 1  and 0.48±0.10 L at t 2  (p tot  in which Qfv was negligible, defined as (t 2 -t 1 )/T tot  averaged 0.33±0.07.  These data suggest that during QB Pab variations produced by diaphragm contraction have a profound modulatory within-breath effect on venous return from the lower limb and this modulation is dependent on Pab dynamics.
Mutational analysis of clinically relevant cancer related genes in colorectal cancer.
Authors: Aine O'Reilly, Colin Barr, Aoife Carr, Elaine Kay, Susan Kennedy, Ray McDermott, William Grogan, David William Fennelly, Oscar S. Breathnach, Des C Winter, Deborah A McNamara, Fergal C Kelleher, John Crown, Bryan Hennessy, Sinead Toomey
Journal: Journal of Clinical Oncology (2015)

615 Background: Whole genome sequencing of colorectal cancer (CRC) has identified common mutations that have been implicated in tumorigenesis. We investigated the association between genetic mutations in known cancer related signaling pathways, and clinicopathological variables in patients with CRC. Methods: DNA samples of patients with CRC were genotyped for Single Nucleotide Polymorphisms (SNPs) including potentially clinically relevant mutations using the Sequenom platform. Results: Tissue from 68 patients was genotyped. 163 mutations were identified in 21 cancer related genes. 45% of patients had stage III CRC &amp; 10% had stage IV CRC at diagnosis. 17 patients developed metastatic CRC. 59 patients had at least 1 mutation. Mutations occurring in at least 5% of patients included KRAS(35%), PIK3R1(34%), TP53(32%), PHLPP2(32%), BRAF(16%), PIK3CA(13%), APC(13%), IDH1(12%), FBXW(7%) &amp; MET(6%). Less frequent mutations (&lt;5%) included GNAS, PTPN, NRAS, STK11, TBX3, and EGFR. KRAS mutations were associated with mucinous histology (P=0.04). TP53 mutations were associated with nodal disease at diagnosis (p=0.03). There was no statistically significant difference in overall survival in patients with KRAS, PIK3, TP53 or BRAF mutations as compared to their wild type (WT) counterparts. No mutation was predictive of disease progression. In patients with mCRC and TP53 mutations, DFS was significantly shorter when mutations in APC, FBXW7, IDH1, MET and NRAS were present (10 months verses 15.5 months p=0.01). Mutations in APC, FBXW7, IDH1, MET and NRAS only occurred in the presence of other mutations. A trend towards reduced DFS was seen in KRAS WT patients with mCRC when mutations in APC, FBXW7, IDH1, MET and NRAS were present (9 months vs. 22 months, p=0.2). A trend towards reduced DFS was seen in patients with mCRC &amp; 3 or more distinct mutations (10 months vs. 18 months p=0.2). Conclusions: These results suggest that mutations in known cancer related signaling pathways occur frequently in patients with CRC. Mutations in APC, FBXW7, IDH1, MET and NRAS conferred a shorter DFS in patients with mCRC &amp;, TP53 mutations, KRAS wild type patients and patients with multiple distinct mutations
Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury
Authors: Nikolaus Wenger, Eduardo Martin Moraud, Jerome Gandar, Pavel Musienko, Marco Capogrosso, Laetitia Baud, Camille G Le Goff, Quentin Barraud, Natalia Pavlova, Nadia Dominici, Ivan R Minev, Leonie Asboth, Arthur Hirsch, Simone Duis, Julie Kreider, Andrea Mortera, Oliver Haverbeck, Silvio Kraus, Felix Schmitz, Jack DiGiovanna, Rubia van den Brand, Jocelyne Bloch, Peter Detemple, Stéphanie P Lacour, Erwan Bézard, Silvestro Micera, Grégoire Courtine
Journal: Nature Medicine (2016)
Phase II trial of intraperitoneal (IP) MHC unrestricted adoptive cell therapy with TALL-104 cells in patients with ovarian carcinoma (OC) with minimal or microscopic residual disease at second look laparotomy/laparoscopy
Authors: P.F. Conte, M. Accoto, F. Nannipieri, Z. Baretta, A. Baldoni, L. Bonanno, V. Guarneri, G. Tasca, E. Di Liso, S. Trasciatti
Journal: Annals of Oncology (2015)
Endothelial dysfunction in patients with chronic obstructive pulmonary disease
Authors: Natalya A. Kuzubova, Elena Surkova, Alexey Yu Gichkin, Olga N. Titova, Mikhail D. Didur
Journal: European Respiratory Journal (2011)

Chronic obstructive pulmonary disease (COPD) is one of important problems of public healthcare. Structural and functional changes in the pulmonary arteries, vascular remodeling has been observed in all COPD patients. Pathophysiologic findings of COPD could be explained by the effects of alveolar hypoxemia, endothelial dysfunction. Endothelin 1 (ET-1) is a vasoactive mediator that causes vasoconstriction and vascular wall proliferation.  The aim of the present study was to investigate systemic endothelial function and some parameters of pulmonary and central circulation in patients with stable moderate and severe COPD.   Methods:  20 COPD patients with 2 stage and 22 COPD patients with 3 stage were under consideration. Endothelial function was determined by Celermajer9s test, plasma level of ET-1 was measured by enzyme-linked immunoassay.   Results:  Reduction of endothelin-depending vascular reaction was determined in 28 patients (66%) with COPD: 18 patients were with severe and 10 patients were with moderate COPD. There was no difference in vasodilatation endothelin-depending function at 14 (34%) patients to compare with control ones. ET-1 level in plasma of COPD patients with 3 stage was higher (p  We conclude: endothelial dysfunction in patients with COPD become intensify from moderate to severe stage, that by-turn influence to increase on central and pulmonary haemodynamics damage.
Gemcitabine: current status of phase I and II trials.
Authors: S B Kaye
Journal: Journal of Clinical Oncology (1994)

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.1994.12.8.1527 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8040662 Gemcitabine: current status of phase I and II trials. S B KayexS B KayeSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.8.1527 First Page PDF © 1994 by American Society of Clinical Oncology
Abstract 17225: Extracellular Signal-Regulated Kinase 1/2 is Essential for Lipocalin-2 Signaling in Endothelial Cells
Authors: Markus Theurl, Andrea Schroll, Igor Theurl, Daniela Lener, Wolfgang-Michael Franz, Guenter Weiss, Rudolf Kirchmair
Journal: Circulation (2014)

Introduction: Lipocalin-2 (Lcn2) is an acute phase protein and a marker of kidney injury. Recently, elevated Lcn2-levels have been reported in heart failure and myocardial infarction. Moreover, stimulation of breast cancer angiogenesis was observed. Thus, we hypothesized that Lcn2 may be a regulator of vascular function and a target for the treatment of ischemic vascular disorders. Methods/Results: In-vitro Lcn2 mediated proliferation of human umbilical vein endothelial cells (HUVEC; rel. proliferation Lcn2 10 nM vs. ctr.: 1.4±0.09, n=3, P&lt;0.001) and human coronary artery endothelial cells (HCAEC; rel. proliferation Lcn2 10 nM vs. ctr.: 1.3±0.07, n=3, P&lt;0.01) as determined by BrdU-incorporation. In the in-vitro matrigel assay stimulation of HUVEC (1.4 fold vs. ctr., n=3, P&lt;0.01) and HCAEC (1.6 fold vs. ctr., n=3, P&lt;0.001) with Lcn2 resulted in a significant induction of capillary like tube formation. All effects were similar to vascular endothelial growth factor (VEGF). Mechanistically these results can be traced back to phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Real-time PCR analyses revealed expression of Lcn2 and its receptor by endothelial cells (EC) as well as a hypoxia-dependent up-regulation (rel. Lcn2 mRNA hypoxia vs. normoxia 1.6±0.2, P&lt;0.05; rel. Lcn2-receptor mRNA hypoxia vs. normoxia 2.6±0.2, P&lt;0.001). In the mouse aortic ring assay Lcn2-treatment resulted in a significant outgrowth of EC similar to VEGF. In the hind limb ischemia (HLI) model Lcn2 -/- mice showed an impressive phenotype. After induction of HLI we detected significantly more tissue defects compared to wild type (WT) mice. The ischemia-related lesions were more severe as determined by necrosis score (necrosis score Lcn2 -/- 1.8±0.2 vs. WT 0.7±0.2, n=5, P&lt;0.01) and amputation rate was significantly higher. In ischemic hind limbs of Lcn2 -/- mice ERK1/2-phosphorylation was almost abrogated which might be an underlying mechanism. Transplantation of WT-bone marrow to irradiated Lcn2 -/- mice didn’t influence the outcome suggesting that observed effects are rather endothelium-dependent than influenced by an inflammatory response. Conclusion: Lcn2 might be a promising therapeutic factor for the treatment of ischemic vascular disorders.
Gastrointestinal stromal tumor (GIST) of the rectum and pararectal space: A French Sarcoma Group (FSG) retrospective review.
Authors: F. Duffaud, P. A. Cassier, A. Adenis, O. Bouche, M. Rios, O. Collard, E. Bompas, S. Chabaud, J. Blay, A. Le Cesne
Journal: Journal of Clinical Oncology (2010)

10055 Background: GIST of rectum and pararectal space are rare entities with limited clinicopathologic series reported. We conducted a retrospective analysis of rectal GIST during the past 9 years in FSG centers. Methods: Patients (pts) with rectal GIST cases were identified in two ways: (1) advanced/metastatic rectal/pararectal GISTs enrolled in the BFR14 trial (36 pts); and (2) a separate group of 45 pts reported via survey from 14 FSG centers. Results: Characteristics for the BFR14 group showed male predominance (57%), median age 62 years, majority of pts (68%) had metastatic GIST. All pts received imatinib (IM), 65% underwent resection of the primary tumor. With a median follow up (FU) of 29 months, the 2-years PFS and OS are 58% and 87% respectively. In the survey group, all rectal GISTs were localized except 5 with metastatic disease. Men were predominant (66%), tumors ranged from asymptomatic (discovered incidentally in 9 pts), to large masses causing pelvic symptoms (pain, bleeding, constipation; in 28 pts), median tumor size was 65 mm (6-130). Twelve pts received preoperative IM therapy (median duration 7 months; 2-10); 8 (67%) experienced PR, 3 minor responses and one had SD. IM treatment allowed sphincter conservation in 7 cases. 40/45 pts underwent surgery. Anterior resection was performed in 13 pts, transanal/transperineal resection in 13 pts, and amputation in 11 pts. Tumor resections were mostly R0/R1 (22/13, 87%), without tumor rupture (72%). 13 tumors had ≤ 5 mitotic index and 21 had >5 mitotic index. Mutations, mostly in exon 11, were documented in 9 of 12 cases. Ten pts received adjuvant IM. With a median FU of 55 months (1-170), 10 pts have died. Twenty pts (50%) developed local recurrence [18 (72%) after surgery alone, 2 (13.5%) after resection combined with preoperative ± postoperative IM], and 8 secondary metastases, in a median of 17 months (5- 87). Conclusions: Preoperative IM treatment results in substantial tumor shrinkage in most pts and facilitates function-preserving surgery. Since rectal GISTs have a high risk for local relapse, postoperative IM should be systematically considered for these pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Pfizer, PharmaMar Amgen, Novartis, Pfizer, PharmaMar Bayer
Evaluation of four different molecular methods for EGFR mutation analysis in exon 18, 19 and 21
Authors: Anna Streubel, Andreas Roth, Susann Stephan-Falkenau, Olfert Landt, Cornelia Götz, Thomas Mairinger
Journal: European Respiratory Journal (2011)

Aims:  EGFR mutation status detection is essential for comprehensive NSCLC treatment Most Non Small Cell Lung Carcinomas are analyzed by histological examination of a biopsy obtained by bronchoscopy. Hence, only a small amount of tissue is available. These conditions require methods,suitable for the detection of very small amounts of mutated DNA. The aim of this study was to compare the sensitivity of mutation detection of four different molecular methods.   Methods:  237 cases with NSCLC were included. All biopsies were formalin fixed and paraffin embedded. DNA was isolated after microdissection of tumor tissue from 20 μm slides, exon 18, 19 and 21 of the EGFR gene were investigated using pyrosequencing (PS) and BioFilm Chip Hybridization (Chip). Additionally, a LightCycler Assay was performed for Exon 19 (LC). All mutations were independently confirmed by Sanger sequencing.   Results:  We determined 197 cases without and 40 with mutations, 26 mutated in Exon 19. Chip: 24 samples, of which 4 mutated, could not be analyzed due to insufficient DNA amplification. Exon 19: 26 out of 26 detected correctly. PS: 39 of 40 mutations were detected. Exon19: 25 out of 26 detedcted correctly. LC (target only Exon 19): 25 of 26 were recognized correctly by this method.   Discussion:  A comparison of methods showed no significant difference in sensitivity. However, the Chipmethod failed to generate a sufficient PCR product out of the microdissected 20 μm slides in every tenth sample. Surprisingly, the LC, based on a clamping-PCR, was not more sensitive than sequencing (PS, Sanger). A clear advantage in sensitivity could not be found for any of the applied methods.
P-202 Molecular confocal laser endomicroscopy (CLE) for the assessment of prognosis in colorectal carcinoma, based on evaluation of putative cancer stem cell markers
Authors: I. Cherciu, T. Cartana, L. Brink, M. Malmstrom, T. Stigaard, P. Klausen, J. Karstensen, H. Hassan, A. Saftoiu, P. Vilmann
Journal: Annals of Oncology (2015)