tbuckley/cabot-search huggingface dataset:
TARIBO trial: Targeted therapy with or without nephrectomy in metastatic renal cell carcinoma (mRCC)—Liquid biopsy for biomarkers discovery.
Authors: Elena Verzoni, Alessandra Bearz, Sergio Bracarda, Marco Bregni, Sebastiano Buti, Saverio Cinieri, Ugo De Giorgi, Giuseppe Fornarini, Luca Galli, Michele Milella, Franco Morelli, Franco Nole, Rodolfo Passalacqua, Roberto Sabbatini, Daniele Santini, Roberto Salvioni, Vera Cappelletti, Paolo Grassi, Filippo G. De Braud, Giuseppe Procopio
Journal: Journal of Clinical Oncology (2016)

TPS4584 Background: Two randomized trials in the cytokine era clearly showed that cytoreductive nephrectomy (CN) increased life expectancy in metastatic renal cell carcinoma (mRCC) patients (pts). The survival benefit of first-line sunitinib and pazopanib has been demonstrated, but the majority of pts enrolled in the pivotal phase III studies had undergone CN. Therefore it is unclear if similar survival benefit could be achieved without CN with these new targeted agents. Methods: A total of 270 mRCC pts will be randomized to receive CN followed by TKIs vs upfront TKIs. Patients will receive pazopanib 800 mg orally daily or sunitinib 50 mg daily, 4 weeks on/ 2 weeks off. The choice of TKI will be done according to investigator’s clinical practice. Primary objective: To compare clinical benefit, as measured by overall survival (OS), provided by CN followed by TKIs vs upfront TKIs in pts with mRCC. Secondary objectives: To compare clinical benefit, as measured by progression-free survival (PFS) and response rate (RR) provided by CN followed by TKIs vs upfront TKIs, Safety. Exploratory study: Evaluation of predictive role of CTCs count and ctDNA at baseline, before and after surgery (in pts undergoing CN), 24 weeks after randomization and at the time of disease progression Key inclusion criteria: Favorable or intermediate MSKCC or Heng prognostic risk group; diagnosis of RCC with a clear-cell component; resectable asymptomatic mRCC with primary in tumor in place; up to 3 different metastatic sites; ≥ 3 metastatic lesions. Key exclusion criteria: Widespread disease ( > or = 4 metastatic organ sites) Oligometastatic disease suitable of metastasectomy ( < 3 lesions confined at one organ site) Statistical plan: The sample size was calculated in order to compare 5-year OS between subjects randomized to receive CN followed by TKIs and those randomized to receive upfront TKIs. A total of 191 deaths will yield 80% power to detect a hazard ratio of 1.5 of upfront TKIs vs CN followed by TKIs with an overall type 1 error of 0.05 (two-sided log-rank test). Such a HR corresponds to an increase in the 5-year OS, from an anticipated value of 10% for TKIs to 21.5% for CN followed by TKIs. Clinical trial information: NCT02535351.
Perforation colique per-coloscopique: le pronostic s'évalue immédiatement et attention aux antécédents chirurgicaux!
Authors: C Tresallet, F Menegaux
Journal: Endoscopy (2006)

La perforation colique iatrogène per-coloscopique est une complication redoutée mais rare. Leur prise en charge est très variable, de l'exploration chirurgicale quasi systématique à la tentative de traitement médical prolongé.
Critical co-diagnostic or ancillary assessment: Germline testing for patients with somatic tumor profiling.
Authors: Edward Esplin, Karen Vikstrom, R. Wesley Munson, Karen Ouyang, Shan Yang, Stephen E Lincoln
Journal: Journal of Clinical Oncology (2016)

e13123 Background: The rapidly expanding use of testing for somatic mutations in tumors by next-generation sequencing (NGS), raises the question of whether, and when, to pair somatic data with germline sequencing of the same patient. A recent study reported 16% of patients with positive tumor profiling (TP) results have a pathogenic variant confirmed in their germline, which has potential implications for the patient’s acute treatment, future surveillance and screening of family members. We studied a series of patients with positive TP results who were referred for germline genetic testing, assessing germline confirmation rate, distribution of confirmed variants and factors contributing to the confirmation rate. Methods: Our study included 40 consecutive cases with a positive result as the indication for for follow-up germline testing. Genomic DNA variants were identified using an NGS-based hereditary cancer panel. Patients’ personal and family histories were obtained from test request forms and were de-identified for this analysis. Results: 16 of 40 TP patients referred for germline genetic testing were confirmed to have likely pathogenic or pathogenic (LP/P) germline variants. The germline confirmations were in BRCA2 (5/16), MUTYH (2/16) and FANCA (2/16), with one confirmed each in: BRCA1, PMS2, PALB2, ATM, MEN1, NF1, and FANCC. Among the clinicians who referred patients for germline testing, the percent positive patient confirmations per clinician varied: 75% of patients for one clinician, 50% for 10 clinicians, 33% for 2 clinicians and 0% for one clinician. Conclusions: The 40% germline confirmation rate is higher than prior reports, and is likely influenced by a clinician-introduced selection bias. The variance among clinicians’ positive confirmation rates suggests there may be important differences in the strategies clinicians use to refer TP patients for germline testing, which deserves further investigation in conjunction with clinicians. ~68% of confirmations were in genes with management guidelines. The confirmation rate in this series suggests a clinical role for germline testing in TP patients, especially for patients whose germline findings have management implications.
Receptor discordance after neoadjuvant chemotherapy and its impact on disease-free survival.
Authors: Deniz Tural, Mustafa Karaca, Bekir Hacioglu, Irem Bilgetekin, Burak Bilgin, Hakan Kocoglu, Gulsum Ozet, Bulent Erdogan, Mehmet Ali Nahit Sendur, Aydin Aytekin, Mustafa Benekli, Ahmet Ozet
Journal: Journal of Clinical Oncology (2016)

e12518 Background: The purposes of this study were to determine estrogen, progesterone and HER2 receptors discordances after neoadjuvant chemotherapy in patients with locally advanced breast cancer and their impacts on disease-free survival (DFS). Methods: Patients hormone and HER2 receptors status were assessed before and after neoadjuvant chemotherapy. Univariate, multivariate analyses, Kaplan Meier and Log-rank test and Cox regression analysis were used Results: Thirty-eight patients had stage II cancer, 148 patients had stage III cancer. One-hundred thirty-eight patients (74%) had hormone receptor positivity and 79 patients (42%) had HER2 positivity. Hormone receptor discordance was detected in 63 patients (34%), HER2 receptor discordance was detected in 33 patients (18%). After neoadjuvant chemotherapy, fifty-three patients with positive hormone receptor had negative hormone receptor status and 24 patients (13%) with positive HER2 receptor had negative HER2 receptor status. Median 5-year DFS in patients who had negative hormone receptor status after chemotherapy while it was positive before chemotherapy was 64%; whereas median 5-year DFS in patients with no change in hormone receptor status after chemotherapy was 79%. But there was no difference between two groups (p = 0.4). Median 5-year DFS in patients who had negative HER2 receptor status after chemotherapy while it was positive before chemotherapy was 50% and patients with no change in HER2 receptor status after chemotherapy was 70%. There was a significant difference between groups (p = 0.003). Pathological complete response(p = 0.04), clinical stage (p = 0.02) and having triple negative tumor (p = 0.001) were statistically significant in univariate analysis. Clinical stage (HR: 3.3, %95 CI: 1.18-9.3, p = 0.022), changing HER2status from positive to negative (HR: 2.6, %95 CI: 1.3-5.1, p = 0.005), and triple negative receptor status (HR: 2.64, %95 CI: 1.3-5.6, p = 0.001) had significantly impact on DFS in multivariate analyses Conclusions: Patients with locally advanced breast cancer had considerably hormone and HER2 receptor discordance after neoadjuvant chemotherapy. Changing HER2 status from positive to negative is an independent risk factor for DFS
Pembrolizumab in Combination with Pomalidomide and Dexamethasone (PEMBRO/POM/DEX) for Pomalidomide Exposed Relapsed or Refractory Multiple Myeloma
Authors: Lilly Wilson, Adam D. Cohen, Brendan M. Weiss, Dan T. Vogl, Alfred L. Garfall, Donna L. Capozzi, Patricia Mangan, Mary Sanchez, Colleen Erb, Edward Stadtmauer
Journal: Blood (2016)
Effect of fewer visits on postnatal depression is important
Authors: D. Tincello
Journal: BMJ (1996)

EDITOR,—Jim Sikorski and colleagues have conducted a large and detailed trial of the benefits and problems associated with different patterns of antenatal care.1 Such studies, examining outcomes such as satisfaction with care, anxieties about the health of the fetus, and the ability of new parents to cope with their baby, are essential to allow proper evaluation of the recommendations in Changing Childbirth, the report of an expert maternity group.2 The authors found that women in …
Silencing of a death associated protein kinase as a pro-survival factor in colon cancer cells
Authors: GA Doherty, SM Byrne, SC Austin, GM Scully, EW Kay, FE Murray, DJ Fitzgerald
Journal: Endoscopy (2005)

Aims: Cyclooxygenase-2 (COX-2) regulates apoptosis in colorectal cancer. We previously identified DRAK2, a pro-apoptotic 'death associated' kinase, as negatively regulated by COX-2 both in-vitro and in-vivo. We aimed to characterise the role of DRAK2 at a cellular level in regulating survival and death in colon cancer cells.
Abstract #5521: Induction of p53 dependent and independent death pathways by targeting cell specific redox systems
Authors: Sivanandane Sittadjody, Thilakavathy Thangasamy, Kirsten H Limesand, Randy Burd
Journal: Cancer Research (2009)

Background:  Glutathione (GSH) and thioredoxin (Trx) play a major role in cellular redox balance and prevent oxidative damage in cells and tissues. In tumors the level of GSH and Trx can be elevated and prevent cell death or apoptosis following chemotherapy or radiation therapy. Hydroxyethyl-disulfide (HEDS) and lipoate (LA) are disulfides that are primarily bioreduced by the GSH and Trx pathways respectively, and can be used to selectively downregulate these redox systems. Quercetin (Qct), an abundant bioflavonoid has been extensively studied because of its redox modulating activity, as well as its ability to inhibit the activity of enzymes involved in signal transduction. Although known as an antioxidant, we have recently shown that high concentrations of quercetin can interfere with disulfide metabolism and can generate ROS. Here we specifically deplete the major bioreduction pathways of different cancer cell lines and demonstrate that intracellular signaling mechanisms can be manipulated to induce cell death via p53-dependent and -independent mechanisms.  Methods:  A549 lung cancer and U87 glioma cells were treated with HEDS and/or LA in the presence or absence Quercetin (75 µM). Protein phosphorylation was determined by Western blot analysis and densitometry. Cell death and ROS was determined by Annexin V-FITC and DCFH-DA staining, respectively.  Results:  A549 cells demonstrated a greater capacity to bioreduce LA, whereas U87 cells showed a greater capacity to bioreduce HEDS. Correspondingly, increased levels of ROS, cell detachment and apoptosis were observed by the combination of Qct plus LA in A549 cells and by Qct plus HEDS in U87 cells. Cell death in both cells lines was associated with reduced levels of phospho-Src and phospho-FAK and inhibition of phosphorylation was greater in the presence of Qct, which has been shown to inhibit protein kinase activities. In U87 cells, phospho-FAK suppressed p53 phosphorylation but depletion of GSH by treatment with HEDS inhibited FAK and induced phosphorylation of p53. Apoptosis was induced in both cell lines and was mediated by p53-dependent (caspase-9) and p53-independent (caspase-8) pathways in the U87 and A549 cells, respectively.  Conclusion:  These results demonstrate that redox levels can be specifically manipulated in the presence of kinase inhibitors to affect the phosphorylation or activation of proteins and enhance cell death. Additionally, knowledge of the cross-talk between cell redox systems and cell signaling or survival pathways will aid in the rational design of small molecule inhibitors.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5521.
Preliminary results from a phase 1 study of the antibody-drug conjugate ABBV-221 in patients with solid tumors likely to express EGFR.
Authors: Emiliano Calvo, James M. Cleary, Victor Moreno, Maryella Gifford, Lisa Roberts-Rapp, Peter J Ansell, Rajendar K. Mittapalli, Ho-Jin Lee, Beibei Hu, David Barch, Christopher Joseph Ocampo, Anthony W. Tolcher
Journal: Journal of Clinical Oncology (2017)

2510 Background: ABBV-221 is a 2 nd -generation antibody-drug conjugate (ADC) targeting EGFR based on the 1 st -generation ADC ABT-414. ABT-414 shows efficacy in glioblastoma (GBM) patients (pts) with EGFR amplification in ongoing studies. ABBV-221 is an affinity matured monoclonal antibody against EGFR linked to the toxin MMAE. ABBV-221 has higher affinity for overexpressed EGFR than ABT-414, potentially allowing it to target a broader range of tumor types. Methods: This is a Phase 1, multicenter study to determine maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) of ABBV-221. Pts are required to have an EGFR-dependent cancer to be eligible. Starting dose of ABBV-221: 0.3 mg/kg IV infused over 3 hrs for each 21-day cycle, with alternate dosing schedules utilized (2 wks on, 1 wk off or weekly) to mitigate infusion reactions. Results: As of 11 January 2017, 42 pts were treated (13 colon, 5 head &amp; neck (H&amp;N) cancer, 5 non-small cell lung cancer, 5 GBM, 2 breast, 12 other). Ten dose escalation cohorts have been completed with the last cleared dose 4.5 mg/kg per cycle. Tumor tissue samples were evaluated for EGFR protein expression by IHC, EGFR and EGFR ligand mRNA expression by RNAseq, and the results compared to outcome. The most common adverse event (AE) was infusion reaction in 18/42 pts (43%); 3 pts experienced severe infusion reactions. Several mitigation strategies were used to permit continued dose escalation. The other most common AE was fatigue in 17/42 pts (41%). Only 1 pt had keratitis (Grade 4). Sixteen pts (38%) had stable disease (SD), including 4 pts who remained on study longer than 6 months. One H&amp;N pt who has received 2 cycles of ABBV-221 had an unconfirmed partial response and continues to be treated. This pt had high levels of both EGFR and EGFR ligand. Preliminary pharmacokinetics (PK) analysis suggests ABBV-221 exposures are approximately dose-proportional. Conclusions: Safety, PK, pharmacodynamics, and preliminary efficacy data of ABBV-221 warrant further study in this population. Infusion reactions have been manageable and primarily a first dose phenomenon. The duration of SD in pts with refractory solid tumors is encouraging. Clinical trial information: NCT02365662.
ERCP versus MRCP: résultats définitifs d'un essai clinique randomisé en cas de probabilité moyenne d'obstruction biliaire
Authors: AN Barkun, J Romagnuolo, C Reinhold, P Burtin, E Valois, M Martel, M Varano, JS Barkun
Journal: Endoscopy (2005)

L'existence de plusieurs méthodes non vulnérantes de cholangiographie nous a conduit à reconsidérer le rôle de la CPRE en cas de suspicion d'obstruction biliaire.
Breast Cancer Screening With Mammography Plus Ultrasonography or Magnetic Resonance Imaging in Women 50 Years or Younger at Diagnosis and Treated With Breast Conservation Therapy
Authors: Nariya Cho, Wonshik Han, Boo-Kyung Han, Min Sun Bae, Eun Sook Ko, Seok Jin Nam, Eun Young Chae, Jong Won Lee, Sung Hun Kim, Bong Joo Kang, Byung Joo Song, Eun-Kyung Kim, Hee Jung Moon, Seung Il Kim, Sun Mi Kim, Eunyoung Kang, Yunhee Choi, Hak Hee Kim, Woo Kyung Moon
Journal: JAMA Oncology (2017)

<h3>Importance</h3> Younger women (aged ≤50 years) who underwent breast conservation therapy may benefit from breast magnetic resonance imaging (MRI) screening as an adjunct to mammography. <h3>Objective</h3> To prospectively determine the cancer yield and tumor characteristics of combined mammography with MRI or ultrasonography screening in women who underwent breast conservation therapy for breast cancers and who were 50 years or younger at initial diagnosis. <h3>Design, Setting, and Participants</h3> This multicenter, prospective, nonrandomized study was conducted from December 1, 2010, to January 31, 2016, at 6 academic institutions. Seven hundred fifty-four women who were 50 years or younger at initial diagnosis and who had undergone breast conservation therapy for breast cancer were recruited to participate in the study. Reference standard was defined as a combination of pathology and 12-month follow-up. <h3>Interventions</h3> Participants underwent 3 annual MRI screenings of the conserved and contralateral breasts in addition to mammography and ultrasonography, with independent readings. <h3>Main Outcomes and Measures</h3> Cancer detection rate, sensitivity, specificity, interval cancer rate, and characteristics of detected cancers. <h3>Results</h3> A total of 754 women underwent 2065 mammograms, ultrasonography, and MRI screenings. Seventeen cancers were diagnosed, and most of the detected cancers (13 of 17 [76%]) were stage 0 or stage 1. Overall cancer detection rate (8.2 vs 4.4 per 1000;<i>P</i> = .003) or sensitivity (100% vs 53%;<i>P</i> = .01) of mammography with MRI was higher than that of mammography alone. After the addition of ultrasonography, the cancer detection rate was higher than that by mammography alone (6.8 vs 4.4 per 1000;<i>P</i> = .03). The specificity of mammography with MRI or ultrasonography was lower than that by mammography alone (87% or 88% vs 96%;<i>P</i> &lt; .001). No interval cancer was found. <h3>Conclusions and Relevance</h3> After breast conservation therapy in women 50 years or younger, the addition of MRI to annual mammography screening improves detection of early-stage but biologically aggressive breast cancers at acceptable specificity. Results from this study can inform patient decision making on screening methods after breast conservation therapy.
Bioprinting: Extrusion Bioprinting of Shear‐Thinning Gelatin Methacryloyl Bioinks (Adv. Healthcare Mater. 12/2017)
Authors: Wanjun Liu, Marcel A. Heinrich, Yixiao Zhou, Ali Akpek, Ning Hu, Xiao Liu, Xiaofei Guan, Zhe Zhong, Xiangyu Jin, Ali Khademhosseini, Yu Shrike Zhang
Journal: Advanced Healthcare Materials (2017)

A novel strategy to directly bioprint cell-laden gelatin methacryloyl (GelMA) constructs using bioinks of GelMA physical gels (GPGs) is developed by Ali Khademhosseini, Yu Shrike Zhang, and co-workers in article number 1601451. Attributed to their shear-thinning and self-healing properties, GPG bioinks containing down to 3% GelMA can retain the shape and form integral structures after deposition, allowing for subsequent UV crosslinking for chemical stabilization.
Etoposide accumulation of AML cells is affected by PSC 833 in vivo and in vitro.
Authors: E Liliemark, Y Wang, U Tidefelt, C Paul, A Gruber, Gunnar Juliusson, Lilian Stenke, M Frostvik-Stolt, R Zhou, B Sundman-Engberg, B Gustavsson, C Pfister, J Liliemark
Journal: Blood (1999)
Activité d'endoscopie digestive et ressources afférentes dans les centres hospitaliers généraux français
Authors: B Denis, P Perrin
Journal: Endoscopy (2005)

L'évaluation des structures consiste à comparer les ressources matérielles, humaines et financières et l'organisation de la structure à un référentiel. Il n'en existe pas en endoscopie digestive. But: état des lieux national de l'activité d'endoscopie digestive, de son organisation et de ses ressources dans les Centres Hospitaliers Généraux (CH) français.
Vaccination establishes clonal relatives of germinal center T cells in the blood of humans
Authors: Antje Heit, Frank Schmitz, Sarah Gerdts, Britta Flach, Miranda S. Moore, Jonathan A. Perkins, Harlan S. Robins, Alan Aderem, Paul Spearman, Georgia D. Tomaras, Stephen C. De Rosa, M. Juliana McElrath
Journal: The Journal of Experimental Medicine (2017)

Germinal center T follicular helper cells (GCTfh) in lymphatic tissue are critical for B cell differentiation and protective antibody induction, but whether GCTfh establish clonal derivatives as circulating memory T cells is less understood. Here, we used markers expressed on GCTfh, CXCR5, PD1, and ICOS, to identify potential circulating CXCR5+CD4+ Tfh-like cells (cTfh) in humans, and investigated their functional phenotypes, diversity, and ontogeny in paired donor blood and tonsils, and in blood after vaccination. Based on T cell receptor repertoire analysis, we found that PD-1-expressing cTfh and tonsillar GCTfh cells were clonally related. Furthermore, an activated, antigen-specific PD1+ICOS+ cTfh subset clonally expanded after booster immunization whose frequencies correlated with vaccine-specific serum IgG; these phenotypically resembled GCTfh, and were clonally related to a resting PD1+ICOS- CD4+ memory T cell subset. Thus, we postulate that vaccination establishes clonal relatives of GCTfh within the circulating memory CD4+CXCR5+PD1+ T cell pool that expand upon reencounter of their cognate antigen.
Silver nanoparticles activate endoplasmic reticulum stress signaling pathway in cell and mouse models: The role in toxicity evaluation
Authors: Lingling Huo, Rui Chen, Lin Zhao, Xiaofei Shi, Ru Bai, Dingxin Long, Feng Chen, Yuliang Zhao, Yan-Zhong Chang, Chunying Chen
Journal: Biomaterials (2015)
A history of multiple concussions does not confer long-term impairments to dynamic cerebral autoregulation
Authors: Alexander D Wright, Jonathan D Smirl, Sarah K Fraser, Kelsey Bryk, Paul van Donkelaar
Journal: British Journal of Sports Medicine (2017)

Objective To examine the effects of concussion history on an index of cerebral autoregulation in a healthy athlete population. Design Retrospective Cohort. Setting Laboratory. Participants 136 male contact sport athletes (19.1±1.4 years, 66 football, 70 hockey) were recruited; 39 presented with 0 previous concussions, 16 with 3+ previous concussions; exclusion criteria included history of concussion within 6 months. Intervention Participants completed baseline testing prior to the athletic season. Squat-stand manoeuvres at 0.05 and 0.10 Hz were used to enhance blood pressure (BP) variation. BP and cerebral blood velocity (CBV) in the middle cerebral artery were indexed non-invasively via finger photoplethysmography and transcranial Doppler ultrasound, respectively. Independent variables included sport (2) and concussion history (2). Outcomes Transfer function analysis point estimates at 0.05 and 0.10 Hz characterised the coherence (correlation), phase (synchronisation), and gain (amplitude buffer) between BP and CBV waveforms during the squat-stand manoeuvres. Results These findings suggest that, despite reductions in 0.10 Hz phase lead being reported acutely after concussion, multiple concussions do not appear to induce long-term impairments in dynamic cerebral autoregulation metrics. This is an important revelation as it indicates that the cerebrovasculature is able to adequately recover following the acutely diminished buffering capacity associated with a concussive injury Conclusions These findings suggest that, despite reductions in 0.10 Hz phase lead being reported acutely after concussion, multiple concussions do not appear to induce long-term impairments in dynamic cerebral autoregulation metrics. This is an important revelation as it indicates that the cerebrovasculature is able to adequately recover following the acutely diminished buffering capacity associated with a concussive injury Competing interests None.