tbuckley/cabot-search huggingface dataset:
Prognostic value of histopathology, stromal tumor infiltrating lymphocytes (sTILs) and adjuvant chemotherapy (AdjCT) in early stage triple negative breast cancer (TNBC).
Authors: Roberto Antonio Leon-Ferre, Mei-Yin Polley, Heshan Liu, Judith A. Gilbert, Victoria Cafourek, David W. Hillman, Ahmed Elkhanany, Margaret Akinhanmi, Vivian Negron, Judy Caroline Boughey, Minetta C. Liu, James N. Ingle, Krishna R. Kalari, Fergus Couch, Daniel W. Visscher, Matthew P. Goetz
Journal: Journal of Clinical Oncology (2017)

533 Background: Current guidelines define TNBC as complete absence of estrogen (ER) and progesterone receptor (PR), without HER2 amplification. However, the prognostic impact of clinical and histopathological factors, sTILs, and AdjCT in TNBC meeting these strict criteria is unknown. Methods: From a cohort of 9985 women who underwent upfront surgery for M0 breast cancer (BC) at Mayo Clinic Rochester from 1985-2012, 1159 pts with ER negative or low (≤10%) BC were identified for central ER/PR/HER2 staining and HER2 FISH (IHC2+ only) to select those with TNBC by modern definitions. Cox proportional hazards models were used to assess the impact of clinicopathological variables on invasive disease-free (IDFS) and overall survival (OS). Results: Tumors from 605 pts (median age 56.3 yrs) met criteria for TNBC (ER &lt; 1%, PR &lt; 1% and HER2 0, 1 or 2+ and FISH negative). 51% were T1, 65% N0, 88% grade 3, and 75% had Ki67 &gt; 15%. Histologically, 39% were anaplastic, 26% invasive ductal, 16% medullary, 8% metaplastic, 6% apocrine and 5% others. Median sTILs was 20% (0-90%). 55% pts received AdjCT [21% anthracycline (A), 19% A + taxane, and 15% other]. Median follow-up for IDFS and OS were 7.4 and 10.6 yrs, respectively. Multivariate analyses demonstrated that higher N stage (p &lt; 0.01), lower sTILs (p = 0.01) and no AdjCT (p &lt; 0.01) were independently associated with worse IDFS and OS. Histology (medullary subtype) was associated with better IDFS in univariate (HR 0.56, 95% CI, 0.35-0.89) but not in multivariate analyses, once sTILs were accounted for. Among systemically untreated pts (n = 182), higher N (p &lt; 0.01) and lower sTILs (p = 0.04) were associated with worse IDFS. For systemically untreated T1N0 pts (n = 111), the 5-yr IDFS was 70% (95% CI, 61-81) [T1a: 83% (95% CI, 63-100), T1b: 68% (95% CI, 52-88) and T1c: 67% (95% CI, 55-83)], compared to 78% (95% CI, 68-84) for T1N0 pts treated with AdjCT. Conclusions: In TNBC pts, N stage, sTILs and receipt of AdjCT were independently prognostic for IDFS and OS. sTILs remained prognostic for IDFS in systemically untreated TNBC. In N0 TNBC, the risk of recurrence or death was substantial in the absence of chemotherapy, even for those with T1 tumors.
Combination effects of Enzastaurin with anti-tumor agents in human tumor cell lines
Authors: Libin Ma, Caroline Wilson, Song Wu, Connie Er, Brian Mullaney, Jeremy Graff, Michael Schroter, Greg Tucker-Kellogg
Journal: Clinical Cancer Research (2007)

C45  Enzastaurin (LY317615.HCl) inhibits signaling through the protein kinase C (PKC)-β and the phosphatidylinositol 3-kinase/AKT pathways, reducing cell proliferation, suppressing tumor-induced angiogenesis, and inducing tumor cell apoptosis. To better understand the role of Enzastaurin in combination therapy, we have conducted systematic studies of selected combination of Enzastaurin with standard chemotherapeutics and targeted agents in relevant human tumor models. High content cellular assays with multiple endpoint readouts, such as proliferation, cell cycle, mitotic index and apoptosis, were used to examine drug combination effects in cell lines grown in monolayer culture. Data were analyzed using InAct software (Integrated Analysis for Combination Therapy). We will present evidence and possible underlying mechanism for ‘greater than additive’ combination effects for Enzastaurin at clinically achievable concentrations in non-small cell lung cancer (NSCLC) cell lines.
Overall and Free-Event Survival of Patients Taken to Hematopoietic Stem Cell Transplantation in a Colombian Reference Center
Authors: Claudia Lucia Sossa Melo, Sara Ines Jimenez Sanguino, Luis Antonio Salazar Montaño, Angela Peña-Castellanos, Sonia Osma, Juan Jose Rey, Miguel Angel Ayala, Nick Tarazona, Edgar David Gomez Laiton, Sandra Rueda Quijano, Jose D Sandoval-Sus
Journal: Blood (2016)
Correction: Corrigendum: SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia
Authors: Constanze Schneider, Thomas Oellerich, Hanna-Mari Baldauf, Sarah-Marie Schwarz, Dominique Thomas, Robert Flick, Hanibal Bohnenberger, Lars Kaderali, Lena Stegmann, Anjali Cremer, Margarethe Martin, Julian Lohmeyer, Martin Michaelis, Veit Hornung, Christoph Schliemann, Wolfgang E Berdel, Wolfgang Hartmann, Eva Wardelmann, Federico Comoglio, Martin-Leo Hansmann, Alexander F Yakunin, Gerd Geisslinger, Philipp Ströbel, Nerea Ferreirós, Hubert Serve, Oliver T Keppler, Jindrich Cinatl
Journal: Nature Medicine (2017)
Secondary Somatic Mutations Restoring <i>RAD51C</i> and <i>RAD51D</i> Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma
Authors: Olga Kondrashova, Minh Nguyen, Kristy Shield-Artin, Anna V. Tinker, Nelson N.H. Teng, Maria I. Harrell, Michael J. Kuiper, Gwo-Yaw Ho, Holly Barker, Maria Jasin, Rohit Prakash, Elizabeth M. Kass, Meghan R. Sullivan, Gregory J. Brunette, Kara A. Bernstein, Robert L. Coleman, Anne Floquet, Michael Friedlander, Ganessan Kichenadasse, David M. O'Malley, Amit Oza, James Sun, Liliane Robillard, Lara Maloney, David Bowtell, Heidi Giordano, Matthew J. Wakefield, Scott H. Kaufmann, Andrew D. Simmons, Thomas C. Harding, Mitch Raponi, Iain A. McNeish, Elizabeth M. Swisher, Kevin K. Lin, Clare L. Scott
Journal: Cancer Discovery (2017)

Abstract High-grade epithelial ovarian carcinomas containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and PARP inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pretreatment and postprogression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase II study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed ovarian carcinoma. In 6 of 12 pretreatment biopsies, a truncation mutation in BRCA1, RAD51C, or RAD51D was identified. In five of six paired postprogression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft, as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations. Significance: Analyses of primary and secondary mutations in RAD51C and RAD51D provide evidence for these primary mutations in conferring PARPi sensitivity and secondary mutations as a mechanism of acquired PARPi resistance. PARPi resistance due to secondary mutations underpins the need for early delivery of PARPi therapy and for combination strategies. Cancer Discov; 7(9); 984–98. ©2017 AACR. See related commentary by Domchek, p. 937. See related article by Quigley et al., p. 999. See related article by Goodall et al., p. 1006. This article is highlighted in the In This Issue feature, p. 920
Cytochrome b5 Reductase 3 Modulates Soluble Guanylate Cyclase Redox State and cGMP Signaling
Authors: Mizanur M. Rahaman, Anh T. Nguyen, Megan P. Miller, Scott A. Hahn, Courtney Sparacino-Watkins, Soma Jobbagy, Nolan T. Carew, Nadiezhda Cantu-Medellin, Katherine C. Wood, Catherine J. Baty, Francisco J. Schopfer, Eric E. Kelley, Mark T. Gladwin, Emil Martin, Adam C. Straub
Journal: Circulation Research (2017)

Soluble guanylate cyclase (sGC) heme iron, in its oxidized state (Fe3+), is desensitized to NO and limits cGMP production needed for downstream activation of protein kinase G-dependent signaling and blood vessel dilation.Although reactive oxygen species are known to oxidize the sGC heme iron, the basic mechanism(s) governing sGC heme iron recycling to its NO-sensitive, reduced state remain poorly understood.Oxidant challenge studies show that vascular smooth muscle cells have an intrinsic ability to reduce oxidized sGC heme iron and form protein-protein complexes between cytochrome b5 reductase 3, also known as methemoglobin reductase, and oxidized sGC. Genetic knockdown and pharmacological inhibition in vascular smooth muscle cells reveal that cytochrome b5 reductase 3 expression and activity is critical for NO-stimulated cGMP production and vasodilation. Mechanistically, we show that cytochrome b5 reductase 3 directly reduces oxidized sGC required for NO sensitization as assessed by biochemical, cellular, and ex vivo assays.Together, these findings identify new insights into NO-sGC-cGMP signaling and reveal cytochrome b5 reductase 3 as the first identified physiological sGC heme iron reductase in vascular smooth muscle cells, serving as a critical regulator of cGMP production and protein kinase G-dependent signaling.
A phase I-II clinical trial with a combination of gemcitabine (GEMZAR) and paclitaxel (TAXOL) for the treatment of refractory multiple myeloma (MM) patients
Authors: Y. Gazitt, G. David Roodman, C. Freytes, P. Shaughnessy, N. Callander, A. Traynor, M. Rothenberg
Journal: Blood (2000)
Impact of atopic dermatitis on health-related quality of life and productivity in adults in the United States: An analysis using the National Health and Wellness Survey
Authors: Laurent Eckert, Shaloo Gupta, Caroline Amand, Abhijit Gadkari, Puneet Mahajan, Joel M. Gelfand
Journal: Journal of the American Academy of Dermatology (2017)

Given its public health impact, there is need for broad and representative data on the humanistic burden of atopic dermatitis (AD).To establish the humanistic burden of AD in US adults.Data were from the 2013 US National Health and Wellness Survey; AD self-reports were propensity-matched with non-AD controls and with psoriasis controls. Bivariate analyses were conducted on burden outcomes between the AD and control groups.Demographics and baseline characteristics were comparable between matched groups. Subjects with AD (n = 349) versus non-AD controls (n = 698) had significantly higher rates of anxiety, depression, and sleep disorders (29.8%, 31.2%, and 33.2% vs 16.1%, 17.3%, and 19.2%, respectively [all P < .001]); a lower Short Form-36 v2 mental component summary score (44.5 vs 48.0, respectively [P < .001]); a lower physical component summary score (47.6 vs 49.5, respectively [P = .004]), and lower health utilities (0.67 vs 0.72, respectively [P < .001]) in addition to a higher work absenteeism rate (9.9% vs 3.6%, respectively [P < .001]) and activity impairment rate (33.6% vs 25.2%, respectively [P < .001]). Subjects with AD and psoriasis controls (n = 260 each) showed similar impairment in health-related quality of life and productivity.Data were self-reported.AD is associated with a substantial humanistic burden that is similar in magnitude to that of psoriasis, which is also recognized for its debilitating symptoms, indicating the need for more effective treatments for AD.
Effect of Ischemia Duration and Protective Interventions on the Temporal Dynamics of Tissue Composition After Myocardial Infarction
Authors: Rodrigo Fernández-Jiménez, Carlos Galán-Arriola, Javier Sánchez-González, Jaume Agüero, Gonzalo J. López-Martín, Sandra Gomez-Talavera, Jaime Garcia-Prieto, Austin Benn, Antonio Molina-Iracheta, Manuel Barreiro-Pérez, Ana Martin-García, Inés García-Lunar, Gonzalo Pizarro, Javier Sanz, Pedro L. Sánchez, Valentin Fuster, Borja Ibanez
Journal: Circulation Research (2017)

The impact of cardioprotective strategies and ischemia duration on postischemia/reperfusion (I/R) myocardial tissue composition (edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction) is not well understood.To study the effect of ischemia duration and protective interventions on the temporal dynamics of myocardial tissue composition in a translational animal model of I/R by the use of state-of-the-art imaging technology.Four 5-pig groups underwent different I/R protocols: 40-minute I/R (prolonged ischemia, controls), 20-minute I/R (short-duration ischemia), prolonged ischemia preceded by preconditioning, or prolonged ischemia followed by postconditioning. Serial cardiac magnetic resonance (CMR)-based tissue characterization was done in all pigs at baseline and at 120 minutes, day 1, day 4, and day 7 after I/R. Reference myocardium at risk was assessed by multidetector computed tomography during the index coronary occlusion. After the final CMR, hearts were excised and processed for water content quantification and histology. Five additional healthy pigs were euthanized after baseline CMR as reference. Edema formation followed a bimodal pattern in all 40-minute I/R pigs, regardless of cardioprotective strategy and the degree of intramyocardial hemorrhage or microvascular obstruction. The hyperacute edematous wave was ameliorated only in pigs showing cardioprotection (ie, those undergoing short-duration ischemia or preconditioning). In all groups, CMR-measured edema was barely detectable at 24 hours postreperfusion. The deferred healing-related edematous wave was blunted or absent in pigs undergoing preconditioning or short-duration ischemia, respectively. CMR-measured infarct size declined progressively after reperfusion in all groups. CMR-measured myocardial salvage, and the extent of intramyocardial hemorrhage and microvascular obstruction varied dramatically according to CMR timing, ischemia duration, and cardioprotective strategy.Cardioprotective therapies, duration of index ischemia, and the interplay between these greatly influence temporal dynamics and extent of tissue composition changes after I/R. Consequently, imaging techniques and protocols for assessing edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction should be standardized accordingly.
Vitamin D and Breast Cancer Survival
Authors: Alain Braillon
Journal: JAMA Oncology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Targeted delivery of CD4+ Th-APC’s stimulatory effect to CD8+ memory T cell responses via acquired synapse-composed pMHC I complexes
Authors: Jim Xiang
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3881 

We previously showed that CD4+ T-helper (Th) cells acquire the by-stander peptide/major histocompatibility complex (pMHC) I and costimulatory CD54 and CD80 by antigen-presenting- cell (APC) stimulation, and act as Th-APC. Here, we further demonstrated that pMHC I and II complexes are in the same lipid raft and CD4+ Th cells acquire pMHC I via internalization/recycling of synapse composed molecules and dissociation-associated and exosomal membrane transfers. Th-APC with acquired APC molecules stimulated antigen (Ag)-specific CD8+ cell responses and antitumor immunity. Interestingly, Th-APC’s stimulatory effect is mediated by its own IL-2 and TNF-Α and acquired CD80 costimulation, and this effect is specifically targeted to Ag-specific CD8+ Tc cells in vivo via acquired pMHC I complexes. These principles will have great impact in antitumor-, auto-immunity and regulatory T cell-dependent immune suppression.
Are There Differences in Disruptions of Reward Processing Between Substance Use Disorder and Gambling Disorder?—Reply
Authors: Arnt F. Schellekens, Maartje Luijten, Guillaume Sescousse
Journal: JAMA Psychiatry (2017)

In Reply Van Holst et al provide a thoughtful comment on our meta-analysis of functional magnetic resonance imaging studies investigating reward processing in addiction.1 Their letter mainly focuses on 2 methodological points.
Clinical outcome and biological predictors of relapse following nephrectomy only for very low risk Wilms tumor (VLR WT): A report from Children’s Oncology Group AREN0532.
Authors: Conrad Vincent Fernandez, Elizabeth Perlman, Elizabeth Anne Mullen, Yueh-Yun Chi, Thomas Edward Hamilton, Kenneth William Gow, Fernando Anthony Ferrer, Douglas C. Barnhart, Peter F. Ehrlich, Geetika Khanna, John A. Kalapurakal, Tina Bocking, Vicki Huff, Qi An, James I. Geller, Paul Edward Grundy, James Robert Anderson, Jeffrey S. Dome, Robert C. Shamberger
Journal: Journal of Clinical Oncology (2015)

10023 Background: An earlier study of observation only following nephrectomy for VLR WT defined as stage I, age < 2 years, favorable histology with a weight<550 grams was suspended for excess relapse. Follow up revealed a higher salvage rate than originally predicted and suggested novel prognostic biomarkers. In this study, we sought to determine if 1) an observation alone strategy in centrally reviewed VLR WT demonstrates an Event Free Survival (EFS) of > 85% and Overall Survival (OS) of > 95%, and 2) to validate prognostic biomarkers. Methods: From 10/30/2006-8/12/2013, 116 eligible patients were enrolled with VLR WT; negative lymph node sampling was required and predisposition syndromes were excluded. All cases had central review of pathology, diagnostic imaging and surgical reports on the AREN03B2 biology and classification study. Evaluable tumors were analyzed for mutation of WT1, 1p and 16q loss of heterozygosity (LOH) using microsatellite analysis, 1q gain, 1p and 16q loss by MLPA, and 11p15 loss or retention of imprinting (LOI, ROI) using methylation restriction sites analysis. Results: Median follow up was 80 months (5-97). Median age was 11.5 months (0.1-23). 12 patients relapsed with no deaths. Estimated 4-year EFS was 89.7% (95% CI 84.1-95.2%) and OS was 100%. 1 patient is alive with disease after 4 relapses. First site of relapse was lung (n=5), tumor bed (n=4), abdomen (n=2), contralateral kidney (n=1). Median time to first relapse was 4.2 months (2.2-43). The presence of intralobar (p=0.46) or perilobar rests (p=1.0) was not associated with relapse, nor was histological subtype (p=0.16). 1q gain, 1p loss and/or 16q loss did not predict relapse, nor did WT1 mutation (but 13/14 with WT1 mutations also had 11p15 LOH). 11p15 methylation status predicted relapse. Conclusions: Most patients meeting VLR criteria can be safely managed by nephrectomy alone. 11p15 LOH/LOI predicts relapse. Future trials considering expansion of an observation alone strategy for low risk WT should incorporate these biomarkers. Clinical trial information: NCT00352534. Relapse No Relapse Yes Total P value 11p15 LOH 32 (80%) 8 (20%) 40 0.0106 11p15 ROI 58 (97%) 2 (3%) 60 11p15 LOI 6 (75%) 2 (25%) 8 Total 96 (89%) 12 (11%) 108
Stemness gene expression profile and correlation with clinicopathologic features (CPfs) in breast cancer (BC) patients (pts).
Authors: Giovanni Benedetti, Mauro Finicelli, Tiziana Squillaro, Barbara Pistilli, Andrea Marcellusi, Paola Mariani, Alfredo Santinelli, Luciano Latini, Antonio Giordano, Umberto Galderisi
Journal: Journal of Clinical Oncology (2014)

1064 Background: Cancer stem cells (CSC) identify a small pool of cells with self-renewal and pluripotency properties responsible of tumor initiation, maintenance and recurrence. The overexpression of genes maintaining pluripotency properties of CSC was described in poorly differentiated BC subtypes. We analyzed a panel of genes, responsible of CSC reprogramming and behaviour in a heterogenous group of BC tissues and correlated the gene expression profile with CPfs and prognosis. Methods: 140 primary invasive BC specimens (luminal A/B/Her2+/TN; n. 21/53/41/25) were collected from operated pts. mRNA expression for SOX2, SOX15, ERAS, SALL4, OCT4, NANOG, UTF1, DPPA2, BMI1, GDF3, ZFP42, KLF4 and TCL1 genes was assessed by RT-PCR. Correlations with molecular subtypes, menopausal status, grading, ER, PR, ki67 (< or > 20%), HER2, T-size and node status (N) were evaluated by Fisher's exact test and χ2 test. Association of stemness genes, CPfs and DFS was estimated by univariate and multivariate Cox-regression analysis (p≤ 0.05) . Results: In 117 samples assessable, 9 out of 13 stemness genes resulted variably expressed: GDF3 = 9, Sox2= 11, ERAS= 20, sox15 = 25, TCL1= 29, Nanog = 52, KLF4 = 67, SALL4 = 68, BMI1 = 97, without any correlation with molecular subtypes. NANOG, GDF3 and SOX2 significantly correlated with grade 2, N negative and higher KI67 respectively (p=0.019, p=0.029, p= 0.035). At univariate analysis SOX2 expression (HR= 2,357; p= 0.002), KI67 (HR= 2,187; p=0.028), N (HR=2,205; p=0.014); ER/PR (HR=0,582/HR=0,589; p0.065/0.068, respectively) resulted statistically significant. According to multivariate analysis, SOX2 (HR= 2,99; 95% CI 1,41-6,30; p=0.004), N (HR=2,44; 95%CI 1,25-4,76; p=0.009) and T-size >1 (HR=1,77; 95% CI=0,99-3,13; p=0.051) were independently associated with increased risk of recurrence, PR expression was associated with better prognosis (HR=0,57; 95% CI= 0,53-0,29; p=0.035). Conclusions: Our analysis confirm that stemness genes are variably expressed in a heterogenous group of BC pts, albeit only specific genes seem to correlate with any CPfs. Of note, SOX2 appeared to be a prognostic marker of recurrence irrespective of other variables.
Гепатологические аспекты метаболического синдрома и возможности патогенетического лечения
Authors: V.V. Cherniavskyi, A.K. Sizenko
Journal: GASTROENTEROLOGY (2014)

Статья посвящена проблеме метаболического синдрома и развитию печеночной недостаточности у пациентов с этой патологией. Приводятся данные, свидетельствующие о целесообразности назначения таким пациентам препарата комплексного действия — орнитина аспартата (оригинальный орнитина аспартат Гепа-Мерц производства «Мерц Фарма ГмбХ и Ко»). Эффективность Гепа-Мерца проявляется уменьшением цитолиза гепатоцитов, нормализацией липидного и углеводного обмена, а также положительным влиянием на клинические проявления печеночной энцефалопатии.