tbuckley/cabot-search huggingface dataset:
Phosphorylated ribosomal S6 (p-S6) as an indicator of HER2 signaling targeted drug resistance.
Authors: Gloria Wangrong YangKolodji, Arjun Mehta, Mike J Gray, Debu Tripathy
Journal: Journal of Clinical Oncology (2013)

609 Background: Thetargeting of HER2/neu oncoprotein with trastuzumab (Herceptin) has altered the natural history of HER2+ breast cancer, however, its clinical benefit is limited by de novo and/or acquired resistance which almost always develops in the advanced setting. While several mechanisms of resistance have been postulated, none are validated for clinical use to best select patients for treatment. Our study aims were to identify predictive biomarkers based on reproducible differences in HER2 initiated signaling pathway observed in trastuzumab-resistant, HER2-overexpressing human breast cell line models. Methods: Exposing HER2+ breast cancer cells BT474 and SKBR3 to 200 µg/ml of trastuzumab for 12 months, we established two trastuzumab-resistant, HER2 overexpressing breast cancer models BtRT and SkRT. MTT assay was used to characterize drug sensitivities of the cells. Immunocytochemistry and immunoblotting were used to assess the expression levels of HER2 signaling pathway proteins. The impact of trastuzumab on cell cycle process was analyzed by FACS. EdU incorporation was adapted to measure cell proliferation. Results: Trastuzumab-resistant cells had a higher proliferation rate and altered expression levels of HER2 signaling pathway proteins such as p-mTOR, p-S6k1, p-Akt, p-S6, and p-4EBP1, in comparison with parental cell lines. A downstream effector of HER2/Akt/mTOR pathway, phosphorylated ribosomal protein S6 (p-S6), was highly expressed and could not be suppressed by trastuzumab in the resistant cells. When the resistant cells were treated with selected HER2/Akt/mTOR pathway targeted drugs including lapatinib, erlotinib, linsitinib, AZD2014, MK-2206, everolimus and BEZ235, the level of p-S6 in these cells was found to be inversely correlated to the drug induced growth inhibition of these cells. Conclusions: p-S6 is a feasible and easy to measure molecular readout of HER2-targeted therapy resistance. This marker is a good candidate for further clinical validation to predict or efficiently measure a patient’s response to HER2/Akt/mTOR targeted drugs and to test novel agents that would reverse resistance and improve the outcome of trastuzumab refractory, HER2 overexpressing breast cancer.
Abstract 16428: Characteristics and Impact of Bystander Cardiopulmonary Resuscitation Following Pediatric Out of Hospital Cardiac Arrest in the United States: A Study From the Cardiac Arrest Registry to Enhance Survival (CARES)
Authors: Maryam Y Naim, Rita V Burke, Bryan F McNally, Robert A Berg, Kimberly Vellano, David Markenson, Richard N Bradley, Joseph W Rossano
Journal: Circulation (2015)

Introduction: Bystander cardiopulmonary resuscitation (BCPR) is associated with improved outcome in adult out-of-hospital cardiac arrest (OHCA). There are few data on the prevalence and impact of BCPR on children. Hypothesis: We aimed to characterize BCPR in pediatric OHCA and test the hypothesis that BCPR would occur infrequently and would be associated with neurologically favorable survival at hospital discharge from a large cardiac arrest registry in the United States. Methods: We conducted an analysis of the Cardiac Arrest Registry to Enhance Survival database. Inclusion criteria were age ≤ 18 years of age and non-traumatic OHCA from January 1, 2013 through December 31, 2014. Neurologically favorable survival was defined as a Cerebral Performance Category Scale of 1 or 2. Results: A total of 2,176 cardiac arrests were evaluated. Most patients were infants (62%) or adolescents (19%). Most arrests occurred at home (86%), were unwitnessed (75%), and had a non-shockable rhythm (93%). BCPR was provided in 49%, most commonly by a family member (71%). BCPR was more common for white (60%) compared to black (42%) and Hispanic children (44%) (p&lt;0.001). Overall, BCPR was associated with a higher rate of neurologically favorable survival (11% vs. 7%, odds ratio [OR]1.6 95% confidence interval [CI] 1.2-2.3). In sub-group analyses, BCPR was associated with a higher rate of neurologically favorable survival for out of home arrests (34% vs. 15%, OR 2.9, 95% CI 1.6-5.3), and arrests presenting in a shockable rhythm (48% vs. 32%, OR 2.0 95% CI 1.0-4.0). For infants BCPR was not associated with survival (6.4% vs. 6.0%, OR 1.1 95% CI 0.7-1.7) or neurologically favorable survival (5.2% vs. 5.0%, OR 1.1 95% CI 0.6-1.8). Conclusion: BCPR was provided in just under 50% of pediatric OHCAs and was more common for white compared to black and Hispanic children. BCPR was associated with improved survival that was most notable in out of home arrests, with over twice as many patients having neurologically favorable survival. Though infants comprised the largest age group, no effect of BCPR outcome was observed. This impact of BCPR suggests the need for a public health strategy to improve the provision of BCPR, and the need for an alternative strategy for some groups including infants.
Multiple Myeloma Staging in Real World Clinical Practice Is Suboptimal: Absence of Beta-2-Microglobulin and Serum Lactase Dehydrogenase Testing Are Limiting Factors
Authors: Noa Biran, Sukhmani Gill, Andrew D Norden, David H. Vesole, Wallace G Stephen, Kenneth D Nahum, David S Siegel, Stuart L. Goldberg
Journal: Blood (2018)
A novel endoscopic morcellator device to facilitate direct necrosectomy of solid walled-off necrosis
Authors: Ahmad Najdat Bazarbashi, Phillip S. Ge, Diogo T. H. de Moura, Christopher C. Thompson
Journal: Endoscopy (2019)

Pancreatic walled-off necrosis (WON) is a feared late complication of acute necrotizing pancreatitis. Pancreatic WON is a well-demarcated, organized collection of necrotic tissue that can occur after severe pancreatitis. Surgical interventions for the treatment of WON have been associated with high morbidity and mortality rates. Endoscopic management including direct endoscopic necrosectomy has emerged as the treatment of choice for WON, with low complication rates, low costs, reduced time of hospitalization, and high rates of WON resolution [1] [2] [3].
Factors influencing outcome in thymic epithelial tumors (TET).
Authors: Ryan Frederick Porter, Milan Radovich, Luis Rojas, Yaman Suleiman, Madison Conces, Kristen L Shirar, Robert P Nelson, Aaron John Spittler, Matthew Burns, Kenneth Kesler, Sunil S. Badve, Bryan P. Schneider, Patrick J. Loehrer
Journal: Journal of Clinical Oncology (2012)

7108 Background: TET represent a heterogeneous collection of rare tumors, thymoma and thymic carcinoma (TC). Prognosis is often based on WHO histology and Masaoka Stage (MS) with small series often lacking long-term follow-up or advance stage disease. We examined predictors of relapse, disease-free survival (DFS) and overall survival (OS) based on WHO classification and MS. Methods: A retrospective analysis was performed on patients(pts) with TET seen at IUSCC from 1976 to 2011 with available tissue blocks. MS, WHO histology, demographics, autoimmune co-existence and non-TET neoplasms were correlated with DFS and OS (via Kaplan-Meier analysis). Results: Of 251 pts identified, MS at diagnosis was I(n=74), II(n=43), III(n=71), IVa(n=38), IVb(n=12) and indeterminate (n=13). The histology were thymoma (n=195) and TC (n=56). Median age was 51(10-88) and (M:F =121:130). Autoimmune disease was present (n=82) (myasthenia gravis n=52) and non-TET neoplasms (n=36). Therapy after diagnosis included surgery alone (n=115), radiation (n=29), chemo (n=71), chemo-radiotherapy (n=29), indeterminate(n=7). Median follow up was 69 months (1 to 399.5). DFS for stages I,II,III at 5 years was 83%, 71% and 39%; DFS was associated with MS (p&lt;.001) and WHO classification (p=.028). The 5yr and 10yr OS for stages I, II, III, IVa, IVb were 90%, 94%, 80%, 55%, 14% and 65%, 52%, 53%, 28%, 0%. The 5yr OS for WHO classification were: A/AB-89%, B1/B2/B3-98% and C-30% and 10yr survivals were 89%, 62%, 0%. OS was associated with MS (p&lt;.01) , WHO classification (p&lt;.001) and autoimmune disease (p=.03). Late relapses (&gt;5yr) occurred in 13 (23%) pts, including 3 with Stage I and 2 with WHO A classification. Conclusions: MS, WHO classification and autoimmune disorders were statistically significant with OS and with DFS for MS and WHO. TC prognosis is significantly worse than thymoma. The improved OS with autoimmune disease requires further investigation but raises the possibility of benefit derived from earlier diagnosis and/or heightened immune surveillance. These data support the notion that all TET, regardless of histologic subtype or clinical stage, are malignant with a capacity for metastasis. As relapses beyond 5 years are common, lifelong follow-up for TET is recommended.
Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery
Authors: Juan J Jimenez-Rivera, Jose L Iribarren-Sarrías, Rafael Martínez-Sanz
Journal: New England Journal of Medicine (2017)

To the Editor: Myles et al. (Jan.12 issue) 1 found that the risk of death was not significantly higher with tranexamic acid than with placebo among patients undergoing cardiac surgery.This drug has a class IA indication for bleeding prophylaxis, decreasing the use of blood products and the risk of reintervention.Doses that are less than 50 mg per kilogram of body weight are effective in preventing bleeding as well as in decreasing the inflammatory response that is associated with cardiopulmonary bypass. 2 Patients with the 5G/G genotype had a greater blood-sparing benefit with the use of tranexamic acid than those with the 4G genotype of the plasminogen-activator inhibitor type 1 polymorphism. 3It will be important for future studies to take into account the pharmacogenomics of tranexamic acid in order to adjust dosing appropriately and to decrease the risk of dose-related adverse effects.
New CXCR1/CXCR2 inhibitors represent an effective treatment for kidney or head and neck cancers sensitive or refractory to reference treatments
Authors: Maeva Dufies, Oleksandr Grytsai, Cyril Ronco, Oumar Camara, Damien Ambrosetti, Anaïs Hagege, Julien Parola, Lou Mateo, Marion Ayrault, Sandy Giuliano, Renaud Grépin, Nathalie Lagarde, Matthieu Montes, Patrick Auberger, Luc Demange, Rachid Benhida, Gilles Pagès
Journal: Theranostics (2019)

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Novel evidence that an alternative complement cascade pathway is involved in optimal mobilization of hematopoietic stem/progenitor cells in Nlrp3 inflammasome-dependent manner
Authors: Mateusz Adamiak, Anna M. Lenkiewicz, Monika Cymer, Magda Kucia, Janina Ratajczak, Mariusz Z. Ratajczak
Journal: Leukemia (2019)
Palbociclib and cetuximab in platinum-resistant and in cetuximab-resistant human papillomavirus-unrelated head and neck cancer: a multicentre, multigroup, phase 2 trial
Authors: Douglas Adkins, Jessica Ley, Prakash Neupane, Francis Worden, Assuntina G Sacco, Kevin Palka, Juneko E Grilley-Olson, Ronald Maggiore, Noha N Salama, Kathryn Trinkaus, Brian A Van Tine, Conor E Steuer, Nabil F Saba, Peter Oppelt
Journal: The Lancet Oncology (2019)
Mycobacterium tuberculosis Beijing genotype strains and unfavourable treatment outcomes: a systematic review and meta-analysis
Authors: Q. Liu, D. Wang, L. Martinez, P. Lu, L. Zhu, W. Lu, J. Wang
Journal: Clinical Microbiology and Infection (2019)

ObjectivesThe Mycobacterium tuberculosis Beijing genotype was first described in 1995 and is now the predominant strain among patients with tuberculosis in many Asian countries. The rapid global spread of the Beijing genotype is receiving increasing attention because it can cause a higher risk of treatment failures. Our objective was to assess the association between the Beijing genotype and unfavourable treatment outcomes of tuberculosis.MethodsWe searched for eligible studies through PubMed, Web of Science, Chinese National Knowledge Infrastructure and Wanfang Data. We included cohort studies that evaluated treatment outcomes and Beijing genotype strains. Participants were individuals with active pulmonary tuberculosis. The association between Beijing genotype and the risk of unfavourable treatment outcomes was assessed using the pooled odds ratios (ORs) with corresponding confidence intervals (CIs).ResultsIn total, 7489 tuberculosis patients were involved in the analysis. Patients infected with the Beijing genotype were more likely to have unfavourable treatment outcomes, with the OR of 2.04 (95% CI 1.52–2.75). The pooled OR was 2.33 (95% CI 1.71–3.16) for recurrence, 2.36 (95% CI 1.69–3.30) for relapse and 2.62 (95% CI 1.90–3.61) for treatment failure, respectively. Subgroup analysis revealed that Beijing genotype was a significant risk factor for unfavourable treatment outcomes in Asians (OR 2.28, 95% CI 1.82–2.86) or in drug-susceptible TB patients (OR 2.11, 95% CI 1.31–3.39). No significant association was observed among non-Asian populations (OR 1.17, 95% CI 0.73–1.86) or patients with multidrug-resistant (MDR) tuberculosis (OR 0.97, 95% CI 0.48–1.94).ConclusionsOur results suggest that Mycobacterium tuberculosis Beijing genotype is associated with an increased risk of unfavourable treatment outcomes, including treatment failure and relapse.
Time to adjuvant chemotherapy (AC) in stage III colon cancer at a community cancer center: A quality improvement initiative.
Authors: Arun Partridge, Mark Rother, Katherine Enright, Leonard Kaizer, Jeffrey A. Myers, Cindy L. Quinton, Sudhashree Rajagopal, Elizabeth Laureen Strevel
Journal: Journal of Clinical Oncology (2013)

e17503 Background: The standard of care for stage III colon cancer remains 5FU based AC. In clinical trial settings, this begins within 56 days of surgery. Recently a meta-analysis suggested that delays to starting chemotherapy are associated with inferior outcomes and the goal should be to commence AC as soon as feasible. Our objective was to assess the time to starting AC for referred patients to our center and to identify modifiable factors which may be improve upon to reduce delays. Methods: All patients referred to our center with stage III colon cancer who received at least 1 cycle of intravenous AC between Jan.1, 2010 and Dec.31, 2010 were identified. Patient characteristics and time intervals between surgery, Medical Oncology referral, Medical Oncology consultation and initiation of AC were assessed. Results: The total number of patients is 43. Median time to initiation of AC from surgery was 60 days with a range of 29-118 days. Only 32% of patients commenced AC within 56 days of surgery. The intervals of time from surgery to Medical Oncology referral and Medical Oncology consultation to initiation of AC were similar with a median of 25 and 26 days respectively. The median time interval from Medical Oncology referral to Medical Oncology consultation was only 9 days. The bulk of the interval for initiation of AC after seeing a Medical Oncologist was for placement of central intravenous (CIV) devices which took a median of 19 days. Conclusions: The majority of our patients do not start AC within an accepted timeframe. Most of the delay is related to the interval taken to request a consultation to Medical Oncology by the surgeon and to Medical Oncology access to CIV devices. Educational programs geared to referring surgeons which stress the importance of timely AC can help and are being initiated. Further options such as pre booking CIV devices and colon cancer patient-specific nurse navigators to try and streamline the processes and reduce their delays are being explored. [Table: see text]
Response by Heeger et al to Letter Regarding Article, “Left Atrial Appendage Isolation in Patients Not Responding to Pulmonary Vein Isolation: Benefit and Risks”
Authors: Christian-Hendrik Heeger, Andreas Rillig, Dominic Geisler, Peter Wohlmuth, Thomas Fink, Shibu Mathew, Roland Richard Tilz, Bruno Reissmann, Christine Lemes, Tilman Maurer, Francesco Santoro, Osamu Inaba, Christian Sohns, YinHao Huang, Hannes Alessandrini, Inge Dotz, Michael Schlüter, Andreas Metzner, Karl-Heinz Kuck, Feifan Ouyang
Journal: Circulation (2019)
Preliminary Results from an Ongoing Phase 1/2 Study of INCB057643, a Bromodomain and Extraterminal (BET) Protein Inhibitor, in Patients (pts) with Advanced Malignancies
Authors: Andres Forero-Torres, Seth Rosen, David C. Smith, Glenn Lesser, Julio Peguero, Shilpa Gupta, Justin M. Watts, Marcus Noel, Razelle Kurzrock, Haeseong Park, Patricia LoRusso, Catherine C. Coombs, Fred Zheng, Julie Switzky, Swamy Yeleswaram, Gerald Falchook
Journal: Blood (2017)
The use and correlation with flow cytometry of fluorescent molecular beacons in real time PCR of IgH gene rearrangements for evaluation of minimal residual disease in multiple myeloma
Authors: O. Kara, A. Yigin, B. Sahin, S. Paydas
Journal: Journal of Clinical Oncology (2006)

17552 Background: At present, the prognostic value of the amount of residual tumor cells in PB, BM or stem cell harvests and its changes over time is stil not clear. Also the advent of new therapeutic approaches to multiple myeloma made necessary the introduction of novel methods for detection of minimal residual disease. Among others approaches residual disease can be detected by using flow cytometry. The aim of the present study was to evaluate a real time PCR test for the IgH gene using alellespecific molecular beacons as fluorescence probes to quantify residual disease and also correlate flow cytometric detection of plasma cells in MM patients during followup after treatment with high dose of chemotherapy or standart chemotherapy. Methods: After clinical diagnosis of 17 MM patients, the CDR1, CDR2 and CDR3 regions of the IgH gene were analysed and sequenced to identify its clonal nature. Unique sequences of the clonal IgH rearrangement were used to design specific molecular beacon probes for each MM patient. We have also examined the co-expression of CD19, CD38, CD45, CD56, and CD138 molecules in cells of bone marrow aspirates in patients with multiple myeloma by flow cytometry. Results: The active disease had been accepted of whom plasma cell infiltration ratio was over 10% in bone marrow and also of whom labeled by CD38 and CD138 by FCM. The detection of the MRD was positive in 13 patients by RT-PCR, respectively. The infiltration ratio was correlated with CD138 expression (p = 0.009) and RT-PCR detection of plasma cells (p = 0.006) and also significant correlation had been found between RT-PCR detection and CD138 expression respectively. No any correlaton was found between other surface antigens (CD38, CD45, CD56). Conclusion: Our results indicated that real time PCR with specific molecular beacons provides a feasible, accurate and reproducible method for the determination of minimal residual disease in MM. By FCM only CD138 expression may have been used as disease marker in addition of the RT-PCR detection. No significant financial relationships to disclose.
FL-DNA approach for noninvasive early diagnosis of colorectal cancer in FOBT-screened patients
Authors: D. Calistri, C. Rengucci, A. Casadei-Gardini, E. Scarpi, W. Zoli, F. Falcini, C. Milandri, D. Amadori, R. Silvestrini
Journal: Journal of Clinical Oncology (2009)

11062 Background: A promising approach for the early diagnosis of colorectal cancer (CRC) is the evaluation of genomic DNA integrity (FL-DNA) extracted from stool. Pilot and confirmatory studies carried out by our group have shown that, thanks to its diagnostic accuracy, this molecular assay could be a useful tool for the non-invasive, early diagnosis of CRC. The aim of the present study was to verify whether the FL-DNA method could represent a valid alternative to the fecal occult blood test (FOBT) or whether it could be used alongside FOBT in screening programs to unmask false FOBT positives and spare patients from unnecessary colonoscopy. For this purpose, stool samples were collected from all individuals participating in the FOBT (OC-Sensor, Alpha Wassermann) Regional Screening Program run by the Cancer Prevention Unit of Morgagni-Pierantoni Hospital in Forli. Methods: The program recruited subjects of either sex aged 50 to 69 years. Of the 560 individuals with FOBT-positive stool subjected to colonoscopy, 26 were diagnosed with adenocarcinoma, 264 with high-grade adenoma and 54 with low-grade adenoma. More than one third (216) of the group had only benign disease (hemorrhoids, diverticulitis, inflammation, etc), hyperplastic polyps or nothing. The integrity of fecal DNA was analyzed blindly by the FL-DNA test on the same specimen used for the occult blood determination. Results: Using a cut-off of 10 ng, the molecular analysis detected over 90% of the colorectal cancers and about 50% of the high- and low-grade adenomas. In particular, diagnostic accuracy was similar for lesions of any localization, level of dysplasia and histopathological characteristic, and higher for lesions &gt; 2 cm and multiple lesions. The test also confirmed its capacity to identify colorectal cancer in asymptomatic individuals. Conclusions: FL-DNA represents a valid alternative to or support for approaches currently used in screening programs. A more in depth DNA stool evaluation in negative FOBT individuals could reveal the test's usefulness in unmasking colorectal tumors and adenomas missed by FOBT. No significant financial relationships to disclose.
Acral melanoma with eccrine involvement: Comments and controversies
Authors: Jorge Magdaleno-Tapial, Cristian Valenzuela-Oñate, José María Ortiz-Salvador, Álvaro Martínez-Doménech, Marta García-Legaz-Martínez, Gemma Pérez-Pastor, Pablo Hernández-Bel, Amparo Pérez-Ferriols, Víctor Alegre-de Miquel
Journal: Journal of the American Academy of Dermatology (2019)
Letter to the Editor: mTOR‐Inhibitor‐Based Immunosuppression Following Liver Transplantation for Hereditary Hemorrhagic Telangiectasia
Authors: Jose Castellote, José Maria Mora Luján, Antoni Riera‐Mestre
Journal: Hepatology (2019)

Potential conflict of interest: Dr. Castellote advises, is on the speakers’ bureau for, and received grants from AbbVie. He advises and received grants from Gilead. He received grants from MSD. To the Editor: We have read with interest the article by Dumortier et al. reporting that patients with hereditary hemorrhagic telangiectasia (HHT) have a high radiological recurrence rate after liver transplantation (LT) with an estimated cumulative risk of 47.9% at 15 years, although clinical consequences in terms of symptomatic liver disease are unknown.1 The immunosuppressant regimen used in these patients was based in calcineurin inhibitors (tacrolimus and ciclosporin) in addition to mycophenolate mofetil when necessary. The authors suggest the possible role of antiangiogenic medications, such as bevacizumab, as adjuvant therapy to LT when radiological recurrent disease appears. However, this drug is expensive, is for intravenous use, has potential severe secondary effects, and has not been tested in patients with LT, and, as the authors comment, HHT vascular growth can recur after bevacizumab withdrawal.1 In a recent study, using heterozygous activin receptor‐like kinase 1 (ALK1) mouse retines and cultured endothelial cells, loss of ALK1 led to increased stalk cell proliferation as a result of overactivation of the phosphatidylinositol 3‐kinase (PI3K) signaling pathway. In the same study, these results were also found using cutaneous telangiectasia biopsies from a small cohort of patients with HHT, in which an increase in endothelial cell proliferation linked to an increase on the PI3K pathway was detected.3 PI3K pathway inhibition with rapamycin normalized endothelial cell hyperproliferation and pericyte coverage in postnatal retinas and stimulated vascular malformations regression in a mouse model.4 Mammalian target of rapamycin (mTOR) inhibitors have been thoroughly tested in patients with LT and are specially recommended in patients with LT for hepatocellular carcinoma.5 We suggest that the use of an mTOR inhibitor–based immunosuppression regimen may be useful for patients with HHT and LT to avoid vascular growth and reduce recurrence rate.