tbuckley/cabot-search huggingface dataset:
Which women with breast cancer do, and do not, undergo receptor status testing? A population-based study.
Authors: Linda Sharp, Marianna De Camargo Cancela, Harry Comber
Journal: Journal of Clinical Oncology (2012)

6036 Background: Receptor status is a determinant of breast cancer (BC) treatment and prognosis. Clinical practice guidelines advise that all women diagnosed with BC may undergo estrogen (ER), progesterone (ER) and human epidermal growth factor 2 (HER2) receptor tests. We conducted a population-based study to investigate what proportions of women undergo testing and predictors of test receipt. Methods: Incident BCs (ICD10 C50) diagnosed 2006-2008 were identified from the National Cancer Registry Ireland. Receptor tests were identified from registration records augmented by review of selected medical records. For each of the three receptors separately, logistic regression was used to identify which socio-demographic (age, marital status, smoking status, area of residence, and deprivation category) and clinical factors (grade, tumour size (T), nodal status (N), distant metastasis (M)) were associated with undergoing testing. Adjusted odds ratios (OR) and 95% confidence intervals were computed. Results: 7619 BCs were included. 7% were not tested for any of the receptors. 73% were tested for all three. Considering each receptor separately, 90% had an ER test, 86% a HER2 test and 80% a PR test. Women with T4 tumours were less likely to have ER and HER2 tests, and more likely to have a PR test, than women with T1 tumours. After adjustment for clinical variables, age was not a significant predictor for ER and HER2 testing, while older women (≥70) were more likely than younger women to have a PR test. For all three tests, non-married women were significantly less likely to be tested (ER: OR=0.65, 95%CI 0.52-0.8; PR: OR=0.81, 95%CI 0.7-,0.93; HER2: OR=0.72, 95%CI 0.62-0.85) and current smokers more likely (ER: OR=1.55, 95%CI 1.14-2.1: PR: OR=1.38, 95%CI 1.15-1.66; HER2: OR=1.25, 95%CI 1.01-1.55). Area of residence at diagnosis was a significant predictor of having each test, although the geographical patterns varied. Conclusions: More than one-quarter of women with BC do not have one or more of the receptor tests. After adjusting for clinical variables, socio-demographic factors were significant predictors of test receipt. In the interests of equity, the reasons underlying these associations should be further investigated.
Correlation of tumor-profiling results with drug selection in ovarian cancer patients.
Authors: Laura K. Shawver, Deborah A. Zajchowski
Journal: Journal of Clinical Oncology (2012)

e15555 Background: With the aim of informing therapy-selection decisions for ovarian cancer patients, we have profiled tumors from 190 ovarian cancer patients since 2008 for expression of 25 biomarkers associated with drug response. For 48 patients with mature follow-up data, we asked how frequently the drugs designated as likely to be of clinical benefit based on the tumor profile were administered. Methods: The tumor profiles and therapeutic choices of 48 patients that received a median of 2 (range 1-9) prior therapies for recurrent disease were extracted from our privacy-protected database. Protein levels of drug sensitivity (ER/PR, hormonal agents; TOPO1, topotecan/irinotecan (T-I); TOP2A, liposomal doxorubicin/etoposide (PLD-E); SPARC, nab-paclitaxel, N-P) and resistance (TS, pemetrexed/capecitabine (PC); RRM1, gemcitabine (G)) markers in each tumor were compared to expression in the ovarian cancer population to assign drugs likely to be associated with clinical benefit (values ≥ 25th percentile: sensitivity; ≤ 25th percentile: resistance). Results: A median of two drugs (range 1-5) were prioritized for each patient based on marker expression. 38 patients received one of the 6 drug classes evaluated by the profile. Of those 38, 22 (58%) received a therapy that correlated with the profile and 16 (42%) received drugs that were not prioritized by the profile. G and PLD were most frequently administered both before (68%) and after (48%) profiling but were supported by the tumor profile in only 40% (4/10: G) and 30% (3/10: PLD-E) of the cases. These frequencies are similar to the patient fraction (26-34%) in which those drugs were each prioritized by profiling, suggesting that the profile is not influencing therapy choice. In contrast, 11 of the 14 patients who received N-P, T-I, or hormonal agents had tumor profiles that prioritized those agents, a frequency of profile match to the treatment received that is higher than expected based on the patient fraction assigned to each therapy. Conclusions: These results require confirmation in a much larger study, but suggest that tumor profiling may guide clinical decision-making for some therapies, although frequently used drugs are often given regardless of the tumor profiling evidence.
THREE-DIMENSIONAL ECHOCARDIOGRAPHIC OVERESTIMATES LEFT VENTRICULAR WALL THICKNESS VERSUS CARDIAC MAGNETIC RESONANCE: A PROSPECTIVE STUDY IN HYPERTROPHIC CARDIOMYOPATHY PATIENTS
Authors: Agostina M. Fava, Anand Mehta, Barbara Bittel, Andrew Bauer, Zoran Popovic, Harry Lever, Per Wierup, Nicholas Smedira, Isadora Sande Mathias, Milind Y. Desai
Journal: Journal of the American College of Cardiology (2020)
HSR20-076: Provider Versus Patient Reported Outcomes (PROs) in Colorectal Cancer (CRC) Patients (pts) Undergoing Systemic Therapy (Ctx): A Real World Experience
Authors: Sonali Agrawal, Caitlin R. Meeker, Sandeep Aggarwal, Elizabeth A. Handorf, Sunil Adige, Efrat Dotan, Crystal S. Denlinger, William H. Ward, Jeffrey M. Farma, Namrata Vijayvergia
Journal: Journal of the National Comprehensive Cancer Network (2020)

"HSR20-076: Provider Versus Patient Reported Outcomes (PROs) in Colorectal Cancer (CRC) Patients (pts) Undergoing Systemic Therapy (Ctx): A Real World Experience" published on 20 Mar 2020 by National Comprehensive Cancer Network.
Induction chemotherapy with paclitaxel and cisplatin followed by concurrent chemoradiation therapy for Stage IIIB non-small cell lung cancer
Authors: G. Lee, K. Kang, J. Kang, H. Kim, J. Jang, J. Lee
Journal: Journal of Clinical Oncology (2006)

17090 Background: We conducted a phase II study of Induction chemotherapy with paclitaxel and cisplatin followed by concurrent chemoradiation in patients with stage IIIB non-small-cell lung cancer to evaluate the response and toxicity profiles. Methods: All enrolled patients were scheduled to receive 2 cycles of induction chemotherapy with paclitaxel (175 mg/m 2 ) intravenous infusion on day 1 and cisplatin (75 mg/m 2 ) intravenously on day 1 every 3 weeks. All non-progressing patients were subsequently treated with concurrent chemoradiation. Concurrent chemoradiation included paclitaxel (60 mg/m 2 ) plus cisplatin (25 mg/m 2 ) intravenously for 6 weeks on day 43, 50, 57, 71, 78, and 85 and once-daily thoracic irradiation. Results: Between July 2000 and October 2005, 39 patients diagnosed as stage IIIB non-small cell lung cancer were enrolled in this study. Four patients achieved a complete response (10.3%) and 21 patients achieved a partial response (53.8 %), for an overall response rate of 64.1% [95% C.I. (49.4%–79.2 %)]. The 1, 2, and 3 year overall survival rate of all 39 patients were 66.7%, 40.6%, and 27.4% respectively, with a median survival time of 20 months. The median progression free survival was 10.7 months [95% C.I. (4.5%–16.9%)]. Esophagitis was the principal toxicity. Grade 3 or 4 esophagitis occurred in 18 patients (45%). Conclusions: Induction chemotherapy with paclitaxel and cisplatin followed by concurrent chemoradiation for stage IIIB non-small cell lung cancer seems to be effective treatment. However, Physicians should also be aware of severe esophagitis to require inpatient parenteral nutrition support and pain control. No significant financial relationships to disclose.
13-gene signature to predict rapid development of brain metastases in patients with HER2-positive advanced breast cancer.
Authors: Renata Duchnowska, Jacek Jassem, Chirayu Pankaj Goswami, Yesim Gokmen-Polar, Lang Li, Mangesh A. Thorat, Natasha Flores, Emily Hua, Stephan Woditschka, Diane Palmieri, Seth M. Steinberg, Wojciech Biernat, Katarzyna Sosinska-Mielcarek, Barbara Szostakiewicz, Bogumila Czartoryska-Arlukowicz, Barbara Radecka, Zorica Tomasevic, George W. Sledge, Patricia Schriver Steeg, Sunil S. Badve
Journal: Journal of Clinical Oncology (2012)

505 Background: Brain metastases (BM) of breast cancer constitute an important part of therapeutic failures and are associated with severe morbidity and mortality. The risk of BM is particularly high in HER2+ advanced breast cancer pts. We earlier developed in this group a 13-gene signature strongly predicting for rapid development of BM (J Clin Oncol 2008; 26: 45s). Now, we validated these results in an independent group of pts and on culture model system. Methods: Discovery group included 87 samples analyzed using cDNA synthesis, annealing, selection, extension, ligation and array hybridization (DASL). Independent validation group included 75 samples analyzed using quantitative reverse-transcriptase PCR. 3D culture validation model system used immortal, non-tumorigenic human MCF10A breast epithelial cells with and without ectopic expression of HER-2 and RAD51, a DNA double strand break repair gene (one of the three genes of this group overexpressed in 13-gene signature). The number and morphology of breast acini were scored using indirect immunoflourescence and confocal microscopy. Results: Median brain metastasis-free survival (BMFS) in the discovery group for ‘high’ vs. ‘low’ expression signature tumors was 36 months and 66 months, respectively (P=0.0068), and in the validation group 54 and 86 months, respectively (P=0.032). Short BMFS was also associated with ER-negativity; BMFS in the cohort of ‘high’ 13-gene signature and ER- tumors vs. other 3 groups was 31 months and 66 months in discovery group, and 41 and 77 months in validation group (P&lt;0.0001 and P=0.02, respectively). Overexpression of RAD51 in MCF-10A breast cells altered their three-dimensional acinar morphology and increased the percentage of invasive structures by 6.5 fold, both in the presence and absence of HER2 overexpression. Conclusions: 13-gene signature and ER-negativity predict rapid development of BM in HER+ advanced breast cancer pts. RAD51 may promote aggressiveness in breast epithelial cells. These data may be useful in the design of BM preventive trials and may prompt new treatment strategies.
IMPACT OF AN INPATIENT-FOCUS INTERVENTION PROGRAM ON HEART FAILURE 30-DAY READMISSION RATE: A PRELIMINARY STUDY
Authors: Yee Yin Hoo, Wan Nurul Huda Wan Hassan, Wardati Mazlan Kepli, Abdul Muizz Abd Malek, Fan Jie Chen, Prashantini Devadas, Yan Yee Chow, Azrol Amar Azizan, Glendon Seng Kiong Lau, Ping Lik Chua
Journal: Journal of the American College of Cardiology (2020)
Potent STING activation stimulates immunogenic cell death to enhance antitumor immunity in neuroblastoma
Authors: Lihong Wang-Bishop, Mohamed Wehbe, Daniel Shae, Jamaal James, Benjamin C. Hacker, Kyle Garland, Plamen P. Chistov, Marjan Rafat, Justin M. Balko, John T. Wilson
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Neuroblastoma (NB) is a childhood cancer for which new treatment options are needed. The success of immune checkpoint blockade in the treatment of adult solid tumors has prompted the exploration of immunotherapy in NB; however, clinical evidence indicates that the vast majority of NB patients do not respond to single-agent checkpoint inhibitors. This motivates a need for therapeutic strategies to increase NB tumor immunogenicity. The goal of this study was to evaluate a new immunotherapeutic strategy for NB based on potent activation of the stimulator of interferon genes (STING) pathway. Methods To promote STING activation in NB cells and tumors, we utilized STING-activating nanoparticles (STING-NPs) that are designed to mediate efficient cytosolic delivery of the endogenous STING ligand, 2’3’-cGAMP. We investigated tumor-intrinsic responses to STING activation in both MYCN-amplified and non-amplified NB cell lines, evaluating effects on STING signaling, apoptosis, and the induction of immunogenic cell death. The effects of intratumoral administration of STING-NPs on CD8 + T cell infiltration, tumor growth, and response to response to PD-L1 checkpoint blockade were evaluated in syngeneic models of MYCN-amplified and non-amplified NB. Results The efficient cytosolic delivery of 2’3’-cGAMP enabled by STING-NPs triggered tumor-intrinsic STING signaling effects in both MYCN-amplified and non-amplified NB cell lines, resulting in increased expression of interferon-stimulated genes and pro-inflammatory cytokines as well as NB cell death at concentrations 2000-fold to 10000-fold lower than free 2’3’-cGAMP. STING-mediated cell death in NB was associated with release or expression of several danger associated molecular patterns that are hallmarks of immunogenic cell death, which was further validated via cell-based vaccination and tumor challenge studies. Intratumoral administration of STING-NPs enhanced STING activation relative to free 2’3’-cGAMP in NB tumor models, converting poorly immunogenic tumors into tumoricidal and T cell-inflamed microenvironments and resulting in inhibition of tumor growth, increased survival, and induction of immunological memory that protected against tumor re-challenge. In a model of MYCN-amplified NB, STING-NPs generated an abscopal response that inhibited distal tumor growth and improved response to PD-L1 immune checkpoint blockade. Conclusions We have demonstrated that activation of the STING pathway, here enabled by a nanomedicine approach, stimulates immunogenic cell death and remodels the tumor immune microenvironment to inhibit NB tumor growth and improve responses to immune checkpoint blockade, providing a multifaceted immunotherapeutic approach with potential to enhance immunotherapy outcomes in NB.
Effect of ABTL0812, a safe dual inhibitor of mTORC1/C2 and dihydrofolate reductase, on gemcitabine and docetaxel cytotoxicity in pancreatic and lung cancer cells.
Authors: Jose Alfon, Jordi Espadaler, Jose A Garcia, Carles Domenech, Jose M Lizcano
Journal: Journal of Clinical Oncology (2013)

e13526 Background: We have previously described that ABTL0812 has oral anticancer properties. The action is exerted through a mechanism of action involving the inhibition of mTORC1 and mTORC2 (mammalian target of rapamycin) pathways and dihydrofolate reductase (DHFR) expression. Administration of ABTL0812 reduced tumor volume similarly or more than standards of care (SOC) in A549 or MiaPaca2 xenografts in mice. Moreover, a 28-day rat toxicity study has shown very low toxicity (NOAEL=500 mg/Kg) good bioavailability and pharmacokinetic linearity, suggesting a broad therapeutic window. A FiM phase I clinical trial in patients with advanced cancer is scheduled to start in June 2013. Methods: Cellular assays were performed in A549 lung adenocarcinoma, and MiaPaca-2 pancreatic carcinoma cells. Cell proliferation was carried out by bromodeoxyuridine (BrdU) incorporation, cell viability by MTT, and protein expression and phosphorylation by immunoblotting. Cellular apoptosis was assessed both by caspase 3 immunoblot and Hoechst 3342 nuclear staining and quantification of nuclei; and autophagy by LC3-II lipidation assay in immunoblots. All studies were performed with ABTL0812 either alone or in combination with SOC. Results: ABTL0812 potentiated the cytotoxic effects of gemcitabine and docetaxel in MiaPaCa-2 and A549 cancer cells, respectively. In MTT assays, the IC 50 ’s of gemcitabine and docetaxel decreased 7 and 80 times in MiaPaca-2 and A549 cells, respectively, when cells were co-incubated with non-cytotoxic ABTL0812 concentrations. Analysis of the activity (Chou and Talalay’s method) revealed that ABTL0812 synergizes with gemcitabine and docetaxel to promote cytotoxicity. We also present data showing the effects of gemcitabine and docetaxel on the molecular targets of ABTL0812 such as Akt and ribosomal S6 phosphorylation, DHFR expression and cellular autophagy. Conversely, we also show the effects of ABTL0182 on cellular apoptosis induced by gemcitabine and docetaxel. Conclusions: ABTL0812 synergistically potentiates the cytotoxic effect of gemcitabine and docetaxel in pancreatic and lung cancer cell models.
Semaphorin 3F signaling actively retains neutrophils at sites of inflammation
Authors: Tracie Plant, Suttida Eamsamarng, Manuel A. Sanchez-Garcia, Leila Reyes, Stephen A. Renshaw, Patricia Coelho, Ananda S. Mirchandani, Jessie-May Morgan, Felix E. Ellett, Tyler Morrison, Duncan Humphries, Emily R. Watts, Fiona Murphy, Ximena L. Raffo-Iraolagoitia, Ailiang Zhang, Jenna L. Cash, Catherine Loynes, Philip M. Elks, Freek Van Eeden, Leo M. Carlin, Andrew J.W. Furley, Moira K.B. Whyte, Sarah R. Walmsley
Journal: Journal of Clinical Investigation (2020)

Neutrophilic inflammation is central to disease pathogenesis, for example, in chronic obstructive pulmonary disease, yet the mechanisms that retain neutrophils within tissues remain poorly understood. With emerging evidence that axon guidance factors can regulate myeloid recruitment and that neutrophils can regulate expression of a class 3 semaphorin, SEMA3F, we investigated the role of SEMA3F in inflammatory cell retention within inflamed tissues. We observed that neutrophils upregulate SEMA3F in response to proinflammatory mediators and following neutrophil recruitment to the inflamed lung. In both zebrafish tail injury and murine acute lung injury models of neutrophilic inflammation, overexpression of SEMA3F delayed inflammation resolution with slower neutrophil migratory speeds and retention of neutrophils within the tissues. Conversely, constitutive loss of sema3f accelerated egress of neutrophils from the tail injury site in fish, whereas neutrophil-specific deletion of Sema3f in mice resulted in more rapid neutrophil transit through the airways, and significantly reduced time to resolution of the neutrophilic response. Study of filamentous-actin (F-actin) subsequently showed that SEMA3F-mediated retention is associated with F-actin disassembly. In conclusion, SEMA3F signaling actively regulates neutrophil retention within the injured tissues with consequences for neutrophil clearance and inflammation resolution.
TRANSCATHETER TRICUSPID VALVE REPAIR USING MITRACLIP: AN ALTERNATIVE THERAPEUTIC OPTION FOR SEVERE FUNCTIONAL TRICUSPID REGURGITATION IN PROHIBITIVE SURGICAL RISK PATIENTS
Authors: Bryan E-Xin Tan, Jian Liang Tan, Ming-Yan Chow, Jeremiah Peter Depta
Journal: Journal of the American College of Cardiology (2020)
Assessment of the relationship between ECOG score and fentanyl pectin nasal spray acceptability scores for breakthrough pain in cancer.
Authors: Luis M. Torres, John D. Conroy, Ravi Tayi, Michael Sidney Perelman, Alastair D. Knight
Journal: Journal of Clinical Oncology (2012)

e19567 Background: Breakthrough pain in cancer (BTPc) involves intermittent episodes of intense pain of limited duration. Prevalence estimates range from 19% to 95% in patients with cancer.Little information is available on how the effectiveness of treatments for BTPc may be affected by patient level of function. Methods: This is a post hoc analysis of data from an open-label, long-term safety study that used fentanyl pectin nasal spray (FPNS, Lazanda, PecFent) for BTPc in patients with ECOG score ≤2. The study included patients who experienced BTPc in spite of background pain that was adequately controlled with at least 60 mg of morphine (or equivalent). Dose of FPNS (100 to 800 mcg) was established during a titration period prior to the open-label phase of the study. The study included assessment of acceptability of FPNS through a 3-question, 4-point scale survey (not satisfied-very satisfied) for ease of use, convenience, and reliability. This analysis assessed acceptability scores grouped by ECOG score after the first 4 weeks of open-label use. Results: There were 195 patients for whom information on baseline ECOG scores and acceptability scores after 4 weeks were reported. For all patients, the ease of use, convenience, and reliability of FPNS were reported as satisfied or very satisfied: 97.4%, 96.9%, and 92.3%, respectively. When sub-grouped by ECOG 0 (n=20), 1 (n=130), and 2 (n=45), results were: ease of use, 100%, 97.7%, 95.6%; convenience, 100%, 96.9%, 95.6%; reliability, 100%, 92.3%, 88.9%, respectively. The percentage of patients who were satisfied or very satisfied with treatment was always high, but increased with level of function, ranging from 88.9% to 95.6% of patients with ECOG score of 2, to 100% of patients with ECOG score of 0. Conclusions: FPNS was well accepted for the treatment of BTPc in patients irrespective of ECOG score (0-2). Overall, more than 90% of patients reported being satisfied or very satisfied with the ease of use, convenience, and reliability of treatment. Patients with lower ECOG scores had slightly higher acceptability scores. Future BTPc studies examining subjective scores should consider differences in ECOG status.
CLINICAL CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH MYOCARDIAL INFARCTION AND CARDIOGENIC SHOCK RECEIVING EXTRACORPOREAL LIFE SUPPORT
Authors: Deepak Acharya, Mohammad Torabi, Mark Borgstrom, Kwan Lee, Karl B. Kern, Ranjith Shetty, Indranee Rajapreyar, Peter Rycus, Joseph Tonna, Peta Alexander, Kapildeo Lotun
Journal: Journal of the American College of Cardiology (2020)
Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial
Authors: Atul Deodhar, Philip S Helliwell, Wolf-Henning Boehncke, Alexa P Kollmeier, Elizabeth C Hsia, Ramanand A Subramanian, Xie L Xu, Shihong Sheng, Prasheen Agarwal, Bei Zhou, Yanli Zhuang, Christopher T Ritchlin
Journal: The Lancet (2020)