tbuckley/cabot-search huggingface dataset:
Free and bound plasmin in esophageal tumors and surrounding tissues in men and women.
Authors: Oleg Ivanovich Kit, Elena Mikhaylovna Frantsiyants, Larisa Kozlova, Yulia A. Pogorelova, Natalya Chugunova, Evgeniy N. Kolesnikov, Michail Averkin, Sergey V. Sanamyants
Journal: Journal of Clinical Oncology (2017)

84 Background: Esophageal squamous cell carcinoma (ESCC) is 2 to 8 times more frequent in men than in women. Tumor progression is directly connected with plasmin participation in destruction of the extracellular matrix and the basement membrane surrounding tumor. The purpose of the study was a comparative analysis of plasminogen (PG), free plasmin (P) and plasmin bound in complex with α 2 -antiplasmin (PAP) in ESCC tissues of men (M) and women (W). Methods: ESCC tumor tissue (T) and its perifocal zone (PZ) were studied by the ELISA (19 men and 8 menopausal women aged 58-72, st II, G2, T 2-3 N 0-1 M 0-1 ). The results were compared to the histologically unchanged tissue from the resection line (RL). PG, P and PAP were measured in 10% homogenates prepared in sterile saline, with recalculation per 1 g wet tissue). Data were processed using Statistica 10. Results: PG content in RL was 1.5 times higher in M than in W. PG in T of M was decreased by 2 times, in W by 3.3 times, in PZ of M – by 2.9 times, in W – by 2.3 times. PG in T and PZ of M was 2.5 and 1.2 times higher than in W. P content in RL of all patients was significantly lower than in other samples, but 1.4 times higher in M than in W. P in T and PZ of M was 3 and 2.5 times higher than in RL, in T and PZ of W – 3.5 and 2.8 times higher than in RL. Significant differences were observed between P levels in T (but not in PZ): 1.3 times higher in M than in W. PAP content was relatively constant in all tissues, with a slight prevalence in T and PZ of W. P/PAP ratio was elevated in all tissues compared to RL, but in T and PZ of M it was 1.4 and 1.2 times higher than in W. P/PAP in RL of M was 1.4 times higher than in W. Conclusions: The results show a higher aggressiveness of P in PZ and T of M, while P formation in T of W was less active. We reported on a higher content of PG activators in T and PZ of M, and taking into account the morbidity statistics and literature data we suppose the effect of androgens on the conditions of PG activation into P and manifestation of its biological features. P in PZ of both M and W can contribute in the expansion of a “tumor field”. P binding in PAP complex was similar in all studied tissues.
EFICACIA Y SEGURIDAD DE LAS PRÓTESIS METÁLICAS AUTOEXPANDIBLES PARA EL TRATAMIENTO DE LAS DEHISCENCIAS POSTQUIRÚRGICAS DE ESÓFAGO
Authors: C Diaz Jaime Francia, M Bustamante Balén, DA Alvarez De Sotomayor Bierman, E Saez Gonzalez, L Argüello Viudez, M Ponce Romero, N Alonso Lazaro, V Pons Beltran
Journal: Endoscopy (2015)

Introducción: Las dehiscencias postquirúrgicas (DP) son una complicación grave de la cirugía esofágica y bariátrica. El tratamiento con prótesis esofágicas metálicas autoexpandibles (SEMS) representa una alternativa a la cirugía buscando un mejor control de la sepsis con menor morbi-mortalidad.
Advanced luminal breast cancer: Who receives chemotherapy as first-line systemic treatment?
Authors: Marta Bonotto, Lorenzo Gerratana, Mauro Mansutti, Stefano Moroso, Stefania Russo, Donatella Iacono, Alessandro Minisini, Gianpiero Fasola, Fabio Puglisi
Journal: Journal of Clinical Oncology (2014)

e11524 Background: Luminal subtypes, divided into 'luminal A' and 'luminal B', are the most prevalent form of breast cancer (BC). Notably, luminal BCs are heterogeneous in terms of molecular characteristics and, ultimately, in terms of patient outcomes. Endocrine therapy (ET) and chemotherapy (CT) are both suitable options as first-line treatment of luminal metastatic BC (MBC). Few data are available about factors that are used in the decision-making process of whether or not to give CT instead of ET, and viceversa, in this patient population. Methods: The study included 335 consecutive patients with ER-positive and/or PgR-positive MBC treated at the Department of Oncology of Udine, Italy, from 2004 to 2013. The cut-off point of 1% was used to define ER and/or PgR positivity. Patient-related and disease-related factors were examined to test the association with first-line treatment choice (ET vs. CT). Results: First-line CT was chosen for 42% of patients. On multivariate analysis, HER2-positivity (OR 11.21, 95%C.I. 3.45-36.473, P<0.0001) and presence of liver metastases (OR 2.29, 95%C.I. 1.08-4.86, P=0.03) were determinants of CT use. Conversely, postmenopausal status (OR 0.35, 95%C.I. 0.14-0.89, P=0.02), age ≥70 years (OR 0.23, 95%C.I. 0.11-0.5, P=0.0002), worse performance status (ECOG 2 vs 0/1; OR 0.25, 95%C.I. 0.07-0.88, P=0.03) and bone only disease (OR 0.11, 95%C.I. 0.04-0.29, P<0.0001) favored ET use. Degree of receptor positivity, MIB-1 status, body mass index, previous treatment for early disease and presence of lung metastases were not associated with treatment choice. Notably, no differences were observed between CT and ET as first-line treatment either in terms of overall survival (OS)(39.94 months and 33.93 months respectively, log-rank test, P=0.3) or progression free survival (PFS) (11.44 months and 9.9 months respectively, log-rank test, P=0.27). Conclusions: The study showed that clinical patient characteristics significantly influenced the decision-making process for the first-line treatment of advanced luminal BC. However, identification of predictive factors that could optimize therapeutic choice is eagerly awaited.
Development and external validation of a prognostic model for metastatic melanoma patients treated with ipilimumab.
Authors: Sara Valpione, Chiara Martinoli, Paolo Fava, Pietro Quaglino, Pier Francesco Ferrucci, Simone Mocellin, Chiara Astrua, Luca Giovanni Campana, Jacopo Pigozzo, Vanna Chiarion-Sileni
Journal: Journal of Clinical Oncology (2015)

e20060 Background: Metastatic melanoma (MM) usually has a dismal prognosis and its treatment options have been deluding for long time: until recently, systemic therapies were limited, with poor response rates and survival advantage. Ipilimumab is a monoclonal anti-Cytotoxic T-Lymphocyte Antigen 4 antibody that demonstrated a survival improvement of MM patients. This study purpose is to define a prognostic model for MM patients treated with ipilimumab. Methods: Prospectively collected data of 113 consecutive MM patients, treated with ipilimumab (3mg/kg, q3w) at Veneto Institute of Oncology (IOV), were analyzed for prognostic factors (patient and melanoma characteristics, relapse-free interval, site and number of metastases, previous therapies) and biomarkers (serum LDH, C-reactive protein, beta2-microglobulin, VEGF, IL2, IL6, S-100, ALP, transaminases, circulating leucocytes, lymphocytes subpopulations). A prognostic model was developed under Cox regression methodology and validated using the data of 69 and 34 patients treated at European Oncology Institute (IEO) and Torino Oncology Department (TO), respectively. Results: After a median survival of 8.3, 4.9 and 7.1 months from first ipilimumab administration, 78, 15 and 10 patients were alive at IOV, IEO and TO, with 24 month survival of 17.7, 17.4 and 26%, respectively. Higher baseline levels of LDH (HR = 2.89, P < .001) and neutrophyls (HR = 1.26, P < .001) were associated with worse prognosis. The model validation gave a C-index of 0.71 at internal validation and 0.70 at external validation. Only patients with neutrophils < 7.5x10^6/l and LDH < 2x upper normal limit survived more than 24 months (p < .001). Conclusions: LDH and neutrophils resulted significant prognostic factors, are feasible for every Center and could be proposed for further validation in melanoma and other immunotherapy settings. A prognostic nomogram was designed and externally validated to help clinicians to identify the patients who would benefit most from ipilimumab, with the purpose to allow a better allocation of resources and avoid toxicities to patient who are at high probability not to respond to treatments.
Outcomes of FOLFIRINOX (FFX) and gemcitabine+nab-paclitaxel (GnP) in initially unresectable locally advanced pancreatic cancer (uLAPC): A population-based study.
Authors: Kelvin K. Chan, Helen Guo, Jaclyn Marie Beca, Ruby Redmond-Misner, Wanrudee Isaranuwatchai, Lucy Qiao, Craig Earle, Scott R. Berry, James Joseph Biagi, Stephen Welch, Brandon Meyers, Nicole Mittmann, Natalie Coburn, Aliya Pardhan, Jessica Arias, Scott Gavura, Erin Diane Kennedy
Journal: Journal of Clinical Oncology (2017)

394 Background: Data regarding the benefits of FFX and GnP in patients (pts) with initially uLAPC is limited. FFX and GnP have been universally publicly funded for first-line uLAPC in Ontario, Canada, since April 2015. The aims of this study are to determine (1) the overall survival (OS) of pts receiving FFX and GnP, (2) the surgical conversion rate of FFX and GnP, and (3) whether resection is associated with better OS in pts with uLAPC in an unselected, real world population. Methods: All pts in Ontario who started first-line FFX, GnP or gemcitabine (G) for uLAPC between April 2015 and March 2016 were identified in Cancer Care Ontario’s New Drug Funding Program database. They were linked to the Ontario Cancer Registry and other population-based databases to ascertain baseline characteristics (age, sex, performance status (PS), locating of tumor, income quintile, and rural residence) and outcomes (pancreatic cancer resection and vital status). Crude and adjusted models of OS were generated using Kaplan-Meier the method and Cox regression. Surgical resection was modelled as a time-dependent variable to examine its association with OS. Results: We identified 147 pts with uLAPC (mean age = 65, 44% female, 31% ECOG PS 0, 61% PS 1, 60% pancreatic head). Ninety (61.2%), 40 (27.2%) and 17 (11.6%) patients were treated with FFX, GnP and G, respectively. With a median follow-up of 7.5 months, median OS was not reached. The 6-month OS rate was 87.8%, 75.1% and 76.4% for FFX, GnP and G, respectively (p = 0.33). Resection occurred in 12 (8.2%) patients, with 10 (11.1%) and 2 (5.0%) treated with FFX and GnP, respectively ( p= 0.34). Surgical resection after initial chemotherapy was not associated with better OS in multivariable analysis (HR 0.26, 95%CI 0.03-1.98, p= 0.19). Conclusions: Pts with uLAPC treated with FFX and GnP appeared to have a reasonable OS in the real world, with &gt; 75% of pts alive at 6 months. Surgical conversion rate in this unselected population appeared to be less than other single institutional studies. The current findings do not appear to show an early surgical benefit, but longer follow-up will be required to assess the potential long-term benefit of surgery.
A novel fragment in stress-induced phosphoprotein 1 (STIP1) with inhibitory effects on cancer cells.
Authors: Tzu-Hao Wang, Chia-Lung Tsai, Angel Chao, Chyong-Huey Lai
Journal: Journal of Clinical Oncology (2015)

e13594 Background: STIP1, a co-chaperone of HSP90 and HSP70, is involved in multiple cellular functions, including protein folding, transcription, RNA splicing, signal transduction, and cell cycle regulation. After we reported that STIP1 can be used as a biomarker for ovarian cancer (Mol Cell Proteomics 2010; Cell Reports 2012; PLoS One 2013), more evidences indicated its elevated expression in other cancers, including endometrial, lung, liver, pancreatic, and colon. We further discovered that a fragment of STIP1, named as peptide 520 (a.a. 520 to 543 of STIP1), inhibited cell growth and triggered apoptosis of cancer cells. Methods: We synthesized peptide 520 with eight arginine residues and a Myc tag, thus it can readily enter the cell and be traced with an anti-Myc antibody. Scrambled peptides with the same a.a. composition of peptide 520 were used as the control peptide. Inhibition of cancer cells by peptide 520 was examined with MTT, LDH, and apoptosis assays and immunofluorescent microscopy. Signaling pathways targeted by peptide 520 were elucidated with siRNA technology, immunoprecipitation, western blot analysis, and proximity ligation assay. In vivo inhibition of cancer tissues was tested in C57BL6 mice with murine ovarian surface epithelial cancer (MOSEC) and immunohistochemical (IHC) studies. Results: In human ovarian cancer tissues, STIP1 protein levels were positively correlated with JAK2. Peptide 520 suppressed in vitro growth of cancer cells, including ovarian cancer MDAH2774 and SKOV3 cells and endometrial cancer ARK2 cells, in a dose-dependent manner. Mechanistically, peptide 520 inhibited JAK2 protein levels and phospho-STAT3 signals, without changing protein levels of total STAT3. Injection of peptide 520 significantly suppressed in vivo MOSEC growth, and IHC of tumor tissues confirmed that peptide 520 suppressed JAK2 and phospho-STAT3. Conclusions: Peptide 520, which is identical to the C-terminal 24 a.a. of STIP1, effectively inhibited cancer growth in vitro and in vivo by inhibiting JAK2 levels and STAT3 phosphorylation. These findings suggest a therapeutic strategy of targeting STIP1 as cancer therapy.
Effect of the combination of the dual mTOR/pI3K inhibitor NVP-BEZ235 with gemcitabine on growth inhibition in pancreatic cancer cells in vitro and in vivo.
Authors: Luise Maute, Johannes Wicht, Martin Zoernig, Manuel Niederhagen, Lothar Bergmann
Journal: Journal of Clinical Oncology (2013)

e15070 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumours and is still associated with a very poor prognosis. Therefore new treatment strategies are needed. The PI3K/AKT and mTOR signaling pathways are frequently dysregulated in PDAC. Thus we investigated the effects of NVP-BEZ235, a novel dual PI3K/mTOR inhibitor, alone or in combination with gemcitabine first in vitro and after promising results also in vivo. Methods: We examined the effect of gemcitabine and NVP-BEZ235 (kindly provided by Novartis Pharma) on cell viability as single agents and in combination with sequential administrations in the four human pancreatic cancer cell lines MiaPaCa-2, Panc-1, AsPC-1 and BxPC-3. For in vivo experiments we used NOD SCID Mice, which were injected with BxPc3 into the right flank. Treatments consisted of Gemcitabine alone, NVP-BEZ235 alone, simultaneous application of both, first application of Gemcitabine followed by NVP-BEZ235 and NVP-BEZ235 followed by Gemcitabine. Results: Simultaneous incubation of gemcitabine and NVP-BEZ235 affected the PDAC cell lines significantly better than the single agent administration. But most effective was a sequential administration of gemcitabine followed by NVP-BEZ235. In vivo Gemcitabine and NVP-BEZ235 as single agents showed a slightly reduced tumor growth and the treatment in the sequence NVP-BEZ235 first, followed by Gemcitabine resulted in only a minimal reduction of tumor growth. The most effective results were obtained by simultaneous and even better in the sequence of Gemcitabine followed by NVP-BEZ235, respectively. Conclusions: The combination of gemcitabine with the dual PI3k/mTOR inhibitor NVP-BEZ235 enhanced the efficacy of PDAC treatment via down-regulation of the DDR related gene Survivin in vitro. This combination seems to be significantly more effective than single agent use in vitro and also in vivo. Furthermore we demonstrated that the sequence of administration of these agents could be a relevant issue. These promising results might offer a new and effective option for the treatment of pancreatic cancer in the future.
Attentional and affective biases for attractive females emerge early in development
Authors: Jennifer Lynn Rennels, Stephanie Ann Verba
Journal: Behavioral and Brain Sciences (2017)

Abstract Predominant experience with females early in development results in infants developing an attractive, female-like facial representation that guides children's attention toward and affective preferences for attractive females. When combined with increased interest in the other sex at puberty, these early emerging biases might help explain the robust prosocial and financial biases men exhibit toward attractive women during adulthood.
Patient safety test will be part of NHS staff appraisals from 2018
Authors: Gareth Iacobucci
Journal: BMJ (2017)

All NHS staff will have to sit an annual multiple choice test on patient safety as part of a drive by England’s health secretary, Jeremy Hunt, to make the service “the world’s largest learning organisation.”

The radical plans, unveiled in a consultation document published on 1 April, will require all NHS staff to sit the test as part of their annual appraisal from 2018. Ministers are understood to have sounded out the production team behind the television quiz show Who Wants To Be …
Patient navigation as a model to increase minority participation in cancer clinical trials.
Authors: Mona Fouad, Aras Acemgil, Sejong Bae, Andres Forero, Michelle Martin, Gabriela R Oates, Edward E. Partridge, Selwyn M. Vickers
Journal: Journal of Clinical Oncology (2015)

6559 Background: For ethical, social, and scientific reasons, cancer clinical trials require participation of patients from diverse population groups. Less than 10% of all patients enrolled in clinical trials are minorities. The patient navigation model has been used to assist under-resourced cancer patients to access medical care. However, the model has not been evaluated as a tool for increasing the participation of minorities in clinical trials. The project “Increasing Minority Participation in Clinical Trials” (IMPaCT) utilized patient navigation (PN) to enhance the recruitment and retention of African Americans (AA) in therapeutic cancer clinical trials in an NCI-designated comprehensive cancer center. Methods: Lay individuals were recruited and trained to serve as PNs for clinical trials. The training curriculum included content related to clinical trials, the navigation process, interaction with patients, the clinical environment, and case management. The training sessions were co-led by clinical research nurses, physicians, and health educators. AA patients potentially eligible for clinical trials were identified through chart review or referrals by clinic nurses, physicians, and social workers. PNs provided two levels of services to AA cancer patients who consented to receive PN support: 1) Clinic-based education about clinical trials; and 2) Tailored supportive services for patients who enrolled in clinical trials. Results: Two lay individuals matching the demographic characteristics of the patients were trained and hired as PNs. Between 2007 and 2014, 424 AA cancer patients were referred to IMPaCT. Of the patients eligible for a clinical trial (N = 378), 302 (79.9%) enrolled in a trial and 270 (71.4%) consented to receive PN support during the trial. Of those receiving PN support, 74.5% completed the trial, compared to 37.5% of those who chose not to receive PN support. The difference in the clinical trial completion rates between participants who received PN support vs. those who did not was statistically significant (P < 0.001; Chi-Square test). Conclusions: This study indicates that PN could address barriers to clinical trial participation in AA cancer patients and improve retention in clinical trials.
A phase I study of veliparib (ABT-888) in combination with weekly carboplatin and paclitaxel in advanced solid malignancies and enriched for triple-negative breast cancer (TNBC).
Authors: Shalu Pahuja, Jan Hendrik Beumer, Leonard Joseph Appleman, Hussein Abdul-Hassan Tawbi, Ronald G. Stoller, James J. Lee, Yan Lin, Fei Ding, Jing Yu, Chandra Prakash Belani, Alice P. Chen, Vincent L. Giranda, Stacie Peacock Shepherd, Edward Chu, Shannon Puhalla
Journal: Journal of Clinical Oncology (2015)

1015 Background: Veliparib (ABT-888) is an oral, potent small molecule inhibitor of poly-ADP-ribose polymerase (PARP). The combination of veliparib (V) with carboplatin (C) and paclitaxel (P) dosed every 3 weeks has been shown to be safe with early signs of efficacy in a phase I study conducted by our group. In breast cancer patients (pts), weekly P improves disease-free and overall survival vs. every three week P with comparable safety (ECOG 1199), thus supporting the exploration of weekly C and P in combination with V. This study is designed to determine the recommended phase 2 dose (RP2D), maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), adverse events (AEs), anti-tumor activity, and pharmacokinetic (PK) parameters of this combination. Methods: A standard 3+3 design was used with 4 escalating V dose levels ranging from 50-200 mg bid. C (AUC 2) and P (80 mg/m2) were administered on a weekly basis over a 21-day cycle on all dose levels. Dose escalation was followed by dose expansion in pts with TNBC with mandatory tumor biopsies. Results: A total of 30 pts were enrolled (median age 52 yr [range 33-83]; 27 female; median prior treatments 3 [range 0-8]; 24 breast [22 TNBC], 2 lung, 1 cervix, 1 ovarian, 1 prostate, 1 gastric). DLTs occurred at the following dose levels: prolonged gr 2 thrombocytopenia at 150 mg bid, and gr 4 neutropenia at 200 mg bid. The RP2D of veliparib was established to be 150 mg bid. The most common all-grade and grade 3/4 AEs included: neutropenia (gr 3/4 in 18 pts [60%]), anemia (gr 3/4 in 5 pts [17%]), and thrombocytopenia (gr 3/4 in 3 pts [10%]). PK parameters of V in this trial were comparable to historical single-agent V. Of the 27 evaluable pts, 13 (48%) responded (1 CR, 12 PR), 10 (37%) had SD, and 4 (15%) had PD. Objective response rate in TNBC was 52%. Among 21 evaluable TNBC pts, response was 60% in BRCA1/2+ pts (3/5 PR), 67% in non-BRCA1/2 pts (1/9 CR; 5/9 PR) and 29% in unknown status pts (2/7 PR). The only ovarian cancer pt was BRCA2+ and had PR. Conclusions: V in combination with weekly C and P was well tolerated with acceptable safety profile. Promising anti-tumor activity was observed, particularly in TNBC. Clinical trial information: NCT01281150.