tbuckley/cabot-search huggingface dataset:
In vitro chemosensitivity assay for patients with gynecologic sarcoma.
Authors: Alessandro Santin, Joyce Varughese, John K. Chan, Candace McClure, Jayanthi Lea
Journal: Journal of Clinical Oncology (2012)

e13078 Background: This study describes the in vitro drug response of gynecologic sarcomas and clinical implications of in vitro testing. Methods: Ovarian or uterine sarcomas were analyzed for response to any of 7 drugs (carboplatin [Carb], cisplatin [Cis], paclitaxel [Ptx], docetaxel [Dtx], doxorubicin [Dox], gemcitabine [Gem], Ifosfamide [Ifo]) with a chemosensitivity assay (ChemoFx, Precision Therapeutics, Inc, Pittsburgh PA). In combination therapy, tumors were considered sensitive if responsive to at least 1 drug. Results: 68 tumors were analyzed (21 ovarian and 47 uterine; 54 primary and 14 recurrent; carcinosarcoma [n=53], leiomyosarcoma [n=13], other [n=2]). 24% of tumors were responsive to Carb, 30% to Cis, 33% to Ptx, 9% to Dtx, 18% to Dox, 26% to Gem, 27% to Ifo, 40% to Carb+Ptx, 39% to Cis+Ifo, 48% to Ptx+Ifo, 24% to Gem+Dtx, and 27% to Gem+Dox (Table). Ovarian sarcomas were more responsive than uterine sarcomas and primary more than recurrent tumors. Carcinosarcomas were more responsive than leiomyosarcomas to Ifo (P=0.02). Conclusions: In vitro tumor response testing may enable physicians to individualize chemotherapy regimens for their patients. [Table: see text]
Is E-cadherin a useful surrogate marker to predict chemo-sensitivity of chemotherapy for triple-negative breast cancer?
Authors: S. Kashiwagi, M. Yashiro, T. Takashima, N. Aomatsu, H. Kawajiri, N. Onoda, B. Nakata, T. Ishikawa, K. Hirakawa
Journal: Journal of Clinical Oncology (2011)

1077 Background: Triple-negative breast cancer (TNBC), which is characterized by negativity for ER, PR, and HER2, is a high risk breast cancer that lacks specific targets for treatment selection. Chemotherapy is therefore the primary systemic modality used in the treatment of this disease, but reliable parameters to predict the chemosensitivity of TNBC have not been clinically available. Methods: This study investigated a consecutive series of 1166 cases of sporadic invasive breast carcinoma except for invasive lobular carcinomas. ER, PR, Ki67 and E-cadherin status were assessed by immunohistochemistry. HER2 status was assessed by either immunohistochemistry or fluorescent in situ hybridization. Results: In postoperative adjuvant therapy, among the 1036 breast cancer cases, 190 (18.3%) revealed a triple-negative phenotype. The cases with E-cadherin loss was frequent (125 of 190 cases) in TNBC. The adjuvant therapy group-especially those with stage II TNBC-had a more favorable prognosis (p=0.0043) than the surgery only group, while there was no significant difference in prognosis between the anthracyclin-based regimen and 5-fluorouracil-based regimen. Patients with E-cadherin-negative and Ki67-positive expression showed significantly (p<0.001) worse overall survival time than those with either E-cadherin-positive or Ki67-negative expression. Multivariate analysis showed that the combination of E-cadherin-negative and Ki67-positive expression was strongly predictive of poor overall survival (p=0.004) in TNBCpatients receiving adjuvant chemotherapy. In neoadjuvant chemotherapy, the pCR rate of all patients was 29.2% (38/130), response rate (RR) was 90.0% (117/130). Significantly reduced E-cadherin expression was noted in 39 of the TNBC group (p<0.001). The pCR rate was significantly higher in TNBC patients with E-cadherin expression (p=0.010). Conclusions: The combination of E-cadherin and Ki67 status might be a useful prognostic marker indicating the need for adjuvant chemotherapy in TNBC patients. And E-cadherin might be a clinically useful marker to predicting the response to neoadjuvant chemotherapy in TNBC.
Is the number of TACE treatments in HCC patients associated with improved survival? A SEER-Medicare population analysis.
Authors: Fadia T. Shaya, Ian Michael Breunig, Nader Hanna, Naimish B. Pandya, Viktor Chirikov, Brian S. Seal, C. Daniel Mullins
Journal: Journal of Clinical Oncology (2012)

210 Background: We examine treatment patterns and associated survival outcomes of TACE at all stages of Hepatocellular Carcinoma in SEER Medicare. Methods: Medicare enrollees, 65 and older, with a diagnosis of a primary HCC between 2000-07 who received treatment were followed through end of 2009 using the Surveillance, Epidemiology and End-Results Program (SEER) and linked Medicare databases, with claims from Medicare parts A and B. Using Cox proportional hazards models, we assessed the impact on mortality, of each additional TACE, systemic chemotherapy, SIRT, external beam radiation therapy, ablation and surgical resection, controlling for cancer stage, general health status, underlying liver disease (alcohol related, Hepatitis B and C, moderate/severe liver dysfunction), and demographics. We assessed overall and HCC-related mortality for all, then for TACE-only treated patients, and stratified outcomes by stage. Results: Out of 3322 treated non-transplant HCC patients, 1094 got TACE, 74% were Caucasian, 6% African American, 66% male, and 45% were at stage 1/2, 17% at stage 3 and 14% at stage 4. Most (56%) received 1, 23% 2, 11% 3 and 10% 4 or more TACEs. In the adjusted models, both overall and HCC mortality reduction were associated with treatment with up to 2 TACEs (HR=0.68, P=&lt;0.001 and HR=0.73, P=&lt;0.001, respectively). A third TACE, but not a fourth, provided a further decrease in overall mortality (0.46, &lt;0.001) and HCC mortality (.45, &lt;0.001). When stratified by stage, the second TACE had a significant marginal effect within Stage 3, and only the first TACE had benefit within Stage 4. No effects were found for TACE in early HCC. In the adjusted models, liver conditions were not associated with HCC mortality among TACE treated patients only. Conclusions: TACE provides a survival benefit for elderly HCC patients in clinical practice. However, the survival benefit may decrease beyond 3 TACE treatments and varies by stage. Additional TACE treatments may be confounded if 4+ TACE treatments are utilized mainly to treat biologically aggressive disease related to extensive tumor burden, advanced disease or recurrences. Treatment selection bias cannot be excluded and should be further explored.
P23 A review of advice given for follow up of lung nodules detected on ct imaging
Authors: H Rostom, R Mogal, S Iyengar
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Pulmonary nodules detected on computed tomography (CT) scanning should be followed-up appropriately, particularly to ensure cases of malignancy are not missed. Direction for this comes through British Thoracic Society (BTS)<sup>1</sup> and Fleischner Society guidelines.<sup>2</sup> We sought to assess whether appropriate advice was provided for follow-up of lung nodules identified on CT images. <h3>Methods</h3> All CT scans undertaken at Wexham Park and Heatherwood Hospitals between July and October of 2015 were searched for the term ‘lung nodule’. This search yielded 152 matches. Scans were subsequently excluded if they were reported as showing ‘no lung nodule(s)’, a nodule in the context of known or metastatic malignancy, and nodules reported as calcified granulomas. The remaining 42 scans were assessed to determine whether advice on follow-up was provided in the radiological report, and whether this was in keeping with existing guidance. <h3>Results</h3> Of the 42 reports included, only fourteen of these (33%) provided any guidance on follow-up. Of these, nine (21% of reports) complied with BTS or Fleischner Society recommendations. The reasons for non-compliance with guidelines when advice was provided were no timescales or follow-up modalities suggested (four of five) and incorrect follow-up time (one of five). Results are summarised in Figure 1. <h3>Conclusions</h3> From our results it is evident that no or incorrect follow-up advice is being given, based on radiological appearances, for the majority (79%) of pulmonary nodules seen on CT imaging. Clearly the potential consequences of this may include malignancy not being detected and managed in a timely fashion. It is therefore fundamental that each unit has a system, based on existing guidelines, to ensure correct advice is provided based on radiological findings. <h3>References</h3> Callister MEJ, Baldwin DR, Akram AR, <i>et al</i>. British thoracic society guidelines for the investigation and management of pulmonary nodules. <i>Thorax</i> 2015;<b>70</b>(Suppl 2):ii1–ii54. Macmahon H, Austin JH, Gamsu G, <i>et al</i>. Guidelines for the management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. <i>Radiology</i> 2005;<b>237</b>(2):395–400.
Pathohistologic findings in patients with nonseminomatous germ cell tumors (NSGCT) who undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for small tumors.
Authors: D. J. Pfister, J. Busch, C. Winter, H. U. Schmelz, K. Dieckmann, P. Albers, M. Schrader, A. Heidenreich
Journal: Journal of Clinical Oncology (2011)

224 Background: The current guidelines recommend the resection of all visible residual tumors in NSGCT after a cisplatin based chemotherapy. There are controversial data concerning the necessity of PC-RPLND in patients with residual tumours less than one centimetre in diameter. The aim of our study was to evaluate the pathological findings in a modern series with regard of the residual tumour size. Methods: A retrospective analysis of the patient's charts was performed including patients who underwent PC-RPLND between 1989 and 2010. Of 408 patients 330 had a NSGCT, 78 patients had a pure seminoma or a primary extragonadal germ cell cancer and were excluded from analysis. The tumour size at the time of surgery was available in 261 patients in the remaining 69 pateints no preopretive data with regard to the tumour size were recorded in the radiology reports. Due to the location of the residual tumour a median laparotomy, a thoracoabdominal approach was used. In one center a laparoscopic approach was preferred. Results: Mean tumour diameter was 4.7 (0 to 32) cm. The patients were stratified in three groups: group 1 n=28 (RT&lt;=1cm), group 2 n=23 (RT&gt;1&lt;=1.5cm) and group 3 n=209 (RT&gt;1.5cm). The histological specimens contained teratoma in 21.4%, 39.1%, 44.5% respectively, viable cancer in 10.7%, 17.4% and 22% respectively, and fibrosis/necrosis in 64.3%, 52.2% and 37.8% respectively in the three grpups respectively. Conclusions: The finding of both teratoma and viable cancer decreases with decreasing sizes of the residual tumour. Nevertheless lesions &lt;= than 1 cm still harbour a significant pathohistology in one third of the patients. As a consequence PC-RPLND must not be omitted even in small RT. No significant financial relationships to disclose.
High Prevalence of Helicobacter pylori (Hp) Infection in Ocular Adnexal Lymphoma (OAL).
Authors: Patricia Validire, Marc Lecuit, Anne Vincent-Salomon, Patricia de Cremoux, Eric Abachin, Corine Plancher, Martine Thioux, Philippe Arnaud, Livia Lumbroso-Le Rouic, Remi Dendale, Bernard Asselain, Jessica Konopka, Rafika Sahli, Didier Decaudin
Journal: Blood (2006)
Results of ENCORE 301, a randomized, phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive (ER+) breast cancer progressing on a nonsteroidal aromatase inhibitor (AI).
Authors: D. A. Yardley, R. Ismail-Khan, P. Klein
Journal: Journal of Clinical Oncology (2011)

268 Background: Hormonal therapy, including AIs, is the mainstay of ER+ breast cancer (BC) treatment; however, both acquired and intrinsic resistance limits its clinical benefit. Entinostat is a novel, oral, class I selective histone deacetylase inhibitor that has been shown to inhibit growth factor signaling pathways that mediate AI resistance. This study was designed to evaluate the impact of the addition of entinostat to exemestane therapy on progression-free survival (PFS). Methods: Postmenopausal women with ER+ advanced BC who had progressed on a non-steroidal AI were randomized to exemestane 25 mg daily + entinostat 5 mg or placebo weekly. Results: A total of 130 women were enrolled (66 exemestane+placebo; 64 exemestane+entinostat). All but 1 patient had Stage IV disease, and 82% had measurable disease. All patients had received prior hormonal therapy (1 prior line 42%; &gt;1 prior line 58%), and 62% had received prior chemotherapy (33% in the advanced BC setting). Analysis of the intent-to-treat population showed that PFS was significantly (defined prospectively as p &lt;0.10) longer with exemestane+entinostat than with exemestane+placebo (4.28 versus 2.27 months, respectively; hazard ratio [HR] = 0.73; p=0.06). Entinostat combined with exemestane was well-tolerated with the most frequent adverse events (AEs) consisting of fatigue, gastrointestinal disturbances, and hematologic abnormalities. AEs with a ≥20% higher incidence with exemestane+entinostat than with exemestane+placebo were fatigue (46% versus 26%, respectively) and uncomplicated neutropenia (25% versus 0%, respectively). The serious AE rate was similar for exemestane+entinostat (13%) and exemestane+placebo (12%). Conclusions: Exemestane+entinostat significantly prolonged the median PFS and reduced the risk of disease progression by 27% versus exemestane+placebo (HR = 0.73). In light of these positive data, a phase III evaluation of this combination is planned.
Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial
Authors: Petr Novak, Reinhold Schmidt, Eva Kontsekova, Norbert Zilka, Branislav Kovacech, Rostislav Skrabana, Zuzana Vince-Kazmerova, Stanislav Katina, Lubica Fialova, Michal Prcina, Vojtech Parrak, Peter Dal-Bianco, Martin Brunner, Wolfgang Staffen, Michael Rainer, Matej Ondrus, Stefan Ropele, Miroslav Smisek, Roman Sivak, Bengt Winblad, Michal Novak
Journal: The Lancet Neurology (2016)
Cell Cycle Deregulation Determines Acute Transformation In Chronic Type Adult T-Cell Leukemia/Lymphoma
Authors: Noriaki Yoshida, Kennosuke Karube, Atae Utsunomiya, Kunihiro Tsukasaki, Yoshitaka Imaizumi, Naoya Taira, Naokuni Uike, Akira Umino, Kotaro Arita, Miyuki Suguro, Shinobu Tsuzuki, Tomohiro Kinoshita, Koichi Ohshima, Masao Seto
Journal: Blood (2013)
Mapping the HLA Ligandome Landscape of Chronic Myeloid Leukemia (CML)—Towards Peptide Based Immunotherapy
Authors: Daniel J. Kowalewski, Mirle Schemionek, Lothar Kanz, Helmut R. Salih, Tim H. Brümmendorf, Vladan Vucinic, Dietger Niederwieser, Hans-Georg Rammensee, Stefan Stevanovic, Juliane S. Stickel
Journal: Blood (2014)
Can skeletomotor action integration occur without consciousness? Evidence from unconscious action inhibition
Authors: Alisabeth Ayars
Journal: Behavioral and Brain Sciences (2016)

Morsella et al. claim that consciousness functions to integrate incompatible skeletal muscle intentions. Their primary cases of conscious skeletomotor integration involve action suppression, such as holding one's breath underwater, which requires suppressing the urge to inhale. This indicates that the authors seem to think action inhibition counts as the relevant kind of integration. I suggest that there is reason to think this kind of inhibition can occur unconsciously via unconscious inhibitory mechanisms. Unconscious inhibition therefore potentially undermines the authors' thesis. If cases of unconscious inhibition are not instances of integration, then the authors should clarify exactly what counts as integration.
Could Chronic Gvhd Overcome the Poor Prognosis of Patients with MDS and TP53 Undergoing Allogeneic HSCT?
Authors: Juan Carlos Caballero, Mercedes Sánchez-Barba, Mónica Del Rey, Kamila Janusz, Eva Lumbreras, María Abáigar, Robledo Cristina, Andrés Jerez, Esperanza Such, Guillermo Sanz, Cristina Calderon, David Valcarcel, Jesus Maria Hernandez-Rivas, María Consuelo Cañizo, María Díez-Campelo
Journal: Blood (2015)
A Phase I Trial of PD 0332991, a Novel, Orally-Bioavailable CDK4/6-Specific Inhibitor Administered in Combination with Bortezomib and Dexamethasone to Patients with Relapsed and Refractory Multiple Myeloma.
Authors: Ruben Niesvizky, Scott Ely, David S Jayabalan, Megan C. Manco, Seema Singhal, Mary Crann, Rachel Courtney, Cynthia DuFresne, Keith D. Wilner, Isan Chen, Tomer Mark, John P. Leonard, Morton Coleman, Maurizio DiLiberto, Xiangao Huang, Selina Chen-Kiang
Journal: Blood (2009)
Study of dynamic contrast-enhanced ultrasound (DCE-US) for the early evaluation of imatinib.
Authors: G. Abboud, N. Lassau, S. Koscielny, B. Benatsou, F. Tabarout, L. Chami, E. Girard, S. Bidault, J. Domont, A. Cioffi, S. Bonvalot, A. Le Cesne
Journal: Journal of Clinical Oncology (2011)

10062 Background: To determine the best timing for the early assessment of a functional parameter calculated with DCE-US in order to select rapidly poor responders from good responders. Methods: All patients had an examination just before the start of imatinib (D-1) and at D7, D14, D30 and D60. Each examination included a bolus injection of 4.8 ml of Sonovue (Bracco) and raw linear data were recorded over 3 minutes with an Aplio (Toshiba). The raw linear data were analyzed with a mathematical model (patent PCT/IB2006/003742) to evaluate one parameter (the area under the curve (AUC) correlated with the blood volume) characterizing the tumor perfusion curve. Response to treatment was evaluated every 2 months with RECIST criteria with scanographic evaluations. Complete or partial responses and stabilization were classified as successes and progression as treatment failure. Results: Since March 2005, 26 patients have been included. The median time to event of of the 6 poor responders was 2 months. The median follow-up of the 20 good responders was 28 months. 109 DCE-US examinations have been performed. Among poor responders: The median variation in the AUC between baseline and D7, 14, 30 and 60 was -19%, -10%, +46% and +86 respectively. In good responders: The variation in the AUC between baseline and D7, 14, 30 and 60 was -20%, -83%, -83% and -88 % respectively. Conclusions: Our results confirm the interest of DCE-US for monitoring imatinib in GIST. The best timing using the AUC is D15 after the beginning of treatment.
Selective Enhancement of Insulin Sensitivity in the Endothelium In Vivo Reveals a Novel Proatherosclerotic Signaling Loop
Authors: Hema Viswambharan, Nadira Y. Yuldasheva, Anshuman Sengupta, Helen Imrie, Matthew C. Gage, Natalie Haywood, Andrew M.N. Walker, Anna Skromna, Natallia Makova, Stacey Galloway, Pooja Shah, Piruthivi Sukumar, Karen E. Porter, Peter J. Grant, Ajay M. Shah, Celio X.C. Santos, Jing Li, David J. Beech, Stephen B. Wheatcroft, Richard M. Cubbon, Mark T. Kearney
Journal: Circulation Research (2016)

Rationale: In the endothelium, insulin stimulates endothelial NO synthase (eNOS) to generate the antiatherosclerotic signaling radical NO. Insulin-resistant type 2 diabetes mellitus is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear. Objective: To answer this question, we generated a mouse with endothelial cell (EC)–specific overexpression of the human insulin receptor (hIRECO) using the Tie2 promoter–enhancer. Methods and Results: hIRECO demonstrated significant endothelial dysfunction measured by blunted endothelium-dependent vasorelaxation to acetylcholine, which was normalized by a specific Nox2 NADPH oxidase inhibitor. Insulin-stimulated phosphorylation of protein kinase B was increased in hIRECO EC as was Nox2 NADPH oxidase–dependent generation of superoxide, whereas insulin-stimulated and shear stress–stimulated eNOS activations were blunted. Phosphorylation at the inhibitory residue Y657 of eNOS and expression of proline-rich tyrosine kinase 2 that phosphorylates this residue were significantly higher in hIRECO EC. Inhibition of proline-rich tyrosine kinase 2 improved insulin-induced and shear stress–induced eNOS activation in hIRECO EC. Conclusions: Enhancing insulin sensitivity specifically in EC leads to a paradoxical decline in endothelial function, mediated by increased tyrosine phosphorylation of eNOS and excess Nox2-derived superoxide. Increased EC insulin sensitivity leads to a proatherosclerotic imbalance between NO and superoxide. Inhibition of proline-rich tyrosine kinase 2 restores insulin-induced and shear stress–induced NO production. This study demonstrates for the first time that increased endothelial insulin sensitivity leads to a proatherosclerotic imbalance between NO and superoxide.
Inhibition of Cytokine Receptor gp130 Signaling in Breast Cancer Cells Markedly Suppresses Secretion of Tissue Factor-Expressing Tumor Microparticles.
Authors: Diego A. de Idiaquez, Dannielle E. Branam, Larry Lamb, Dongquan Chen, Lihong Teng, Katri S. Selander, Kevin W. Harris
Journal: Blood (2005)
T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer
Authors: Eric Tran, Paul F. Robbins, Yong-Chen Lu, Todd D. Prickett, Jared J. Gartner, Li Jia, Anna Pasetto, Zhili Zheng, Satyajit Ray, Eric M. Groh, Isaac R. Kriley, Steven A. Rosenberg
Journal: New England Journal of Medicine (2016)

We identified a polyclonal CD8+ T-cell response against mutant KRAS G12D in tumor-infiltrating lymphocytes obtained from a patient with metastatic colorectal cancer. We observed objective regression of all seven lung metastases after the infusion of approximately 1.11×1011 HLA-C*08:02-restricted tumor-infiltrating lymphocytes that were composed of four different T-cell clonotypes that specifically targeted KRAS G12D. However, one of these lesions had progressed on evaluation 9 months after therapy. The lesion was resected and found to have lost the chromosome 6 haplotype encoding the HLA-C*08:02 class I major histocompatibility complex (MHC) molecule. The loss of expression of this molecule provided a direct mechanism of tumor immune evasion. Thus, the infusion of CD8+ cells targeting mutant KRAS mediated effective antitumor immunotherapy against a cancer that expressed mutant KRAS G12D and HLA-C*08:02.
Cortactin Is Overexpressed In Neoplastic Cells of Patients with B-Cell Chronic Lymphocytic Leukemia
Authors: Livio Trentin, Cristina Gattazzo, Veronica Martini, Federica Frezzato, Valentina Trimarco, Anna Cabrelle, Valeria Olivieri, Francesca Zonta, Elena Tibaldi, Anna Maria Brunati, Renato Zambello, Gianpietro Semenzato
Journal: Blood (2010)
Trends in Palliative Care Use in Elderly Men and Women With Severe Heart Failure in the United States—Reply
Authors: Anant Mandawat, Paul A. Heidenreich, Deepak L. Bhatt
Journal: JAMA Cardiology (2016)

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