tbuckley/cabot-search huggingface dataset:
Dichotomous ALK-IHC Is a Better Predictor for ALK Inhibition Outcome than Traditional ALK-FISH in Advanced Non–Small Cell Lung Cancer
Authors: A.J. van der Wekken, R. Pelgrim, N. 't Hart, N. Werner, M.F. Mastik, L. Hendriks, E.H.F.M. van der Heijden, M. Looijen-Salamon, A.J. de Langen, J. Staal-van den Brekel, S. Riemersma, B.E. van den Borne, E.J.M. Speel, A-M.C. Dingemans, T.J.N. Hiltermann, A. van den Berg, W. Timens, E. Schuuring, H.J.M. Groen
Journal: Clinical Cancer Research (2017)

Purpose: ALK rearrangement detection using FISH is the standard test to identify patients with non-small cell lung carcinoma (NSCLC) eligible for treatment with ALK inhibitors. Recently, ALK protein expression in resectable NSCLC showed predictive value. We evaluated tumor response rate and survival after crizotinib treatment of patients with advanced NSCLC with ALK activation using both dichotomous immunohistochemical (IHC) staining and FISH.Experimental Design: Patients with stage IV NSCLC treated with crizotinib were selected. Tumor response was assessed. ALK rearrangements were detected by FISH (Vysis ALK-break-apart FISH-Probe KIT) and IHC [Ventana ALK (D5F3) CDx assay]. Cohorts of patients with ALK-FISH-positive advanced NSCLC from four other hospitals were used for validation.Results: Twenty-nine consecutive patients with ALK-positive advanced NSCLC diagnosed by FISH and/or IHC on small biopsies or fine-needle aspirations (FNA) were treated with ALK inhibitors. All ALK-IHC-positive patients responded to crizotinib except three with primary resistance. No tumor response was observed in 13 ALK-FISH-positive but ALK-IHC-negative patients. This was confirmed in an external cohort of 16 patients. Receiver operator characteristic (ROC) curves for ALK-IHC and ALK-FISH compared with treatment outcome showed that dichotomous ALK-IHC outperforms ALK-FISH [tumor response area under the curve: (AUC), 0.86 vs. 0.64, P = 0.03; progression-free survival (PFS): AUC 0.86 vs. 0.36, P = 0.005; overall survival (OS): AUC, 0.78 vs. 0.41, P = 0.01, respectively].Conclusions: Dichotomous ALK-IHC is superior to ALK-FISH on small biopsies and FNA to predict tumor response and survival to crizotinib for patients with advanced NSCLC. Our data strongly suggest adapting the guidelines and using dichotomous ALK-IHC as standard companion diagnostic test to select patients with NSCLC who benefit from ALK-targeting therapy. Clin Cancer Res; 23(15); 4251-8. ©2017 AACR.
Endobronchial ultrasound-guided transbronchial needle aspiration samples for multiple molecular analysis.
Authors: Kezhong Chen, Fan Yang, Hui Zhao, Jun Wang
Journal: Journal of Clinical Oncology (2012)

75 Background: We assessed the usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to detect EGFR, K-ras, ALK mutations from malignant mediastinal nodes of patients with NSCLC. Methods: From February 2010 to April 2012, 81 specimens diagnosed with lung adenocarcinoma by EBUS were used for molecular analysis. Needle puncture site for the EBUS was standard 22G needle, once cytology pathology diagnosed adenocarcinoma, at the same site with the conventional needle puncture method to obtain adequate biopsy specimen for further analysis. The tissue was fixed in 10% formalin. When histologic diagnosis confirmed adenocarcinoma, the FFPE tissue was extracted DNA to detect EGFR mutation by both amplification refractory mutation system (ARMS) and direct sequencing. Partial specimens also extracted DNA or RNA to detect K-ras and ALK mutation. Results: 80/81 specimens were successfully extracted DNA, 52 were male and 28 were female, mean age of 62.9 years (34 to 82 years). Somatic mutations of the EGFR gene were detected in 37 of 80 cases (46.3%), 22 cases of exon 19 mutation,14 cases of exon 21 mutation, and 1 of T790M mutation in ARMS. The result have some difference in direct sequening. In the patients who requested other biomarkers analysis, 6 had K-ras mutations and 2 had ALK mutations.7 patients with EGFR mutations had a radical surgery after neoadjuvant chemotherapy, tumor specimens were tested again with EGFR gene mutation, the same result as the preoperative test results. Conclusions: EBUS-TBNA mediastinal lymph node biopsy in the detection of EGFR, K-ras, and ALK mutations in tissue samples was feasible, through the highly sensitive methods, higher detection rate was available, the result can be used as evidence of personalized treatment of lung cancer.
A Subset of Chronic Myeloid Leukemia (CML) Patients on ABL Kinase Inhibitor Therapy Develop Point Mutations outside the BCR-ABL Kinase Domain That Decrease Drug Sensitivity and May Have a Role in Disease Progression.
Authors: Daniel W. Sherbenou, Oliver Hantschel, Stephanie Willis, Richard D. Press, Brian J. Druker, Giulio Superti-Furga, Michael W. Deininger
Journal: Blood (2006)
Chemotherapy in metastatic hormone-naïve prostate cancer: Pooled analysis of randomized clinical trials.
Authors: Paolo Fabbri, Lucia Stocchi, Stefania Nicoletti, Fabrizio Drudi, Emiliano Tamburini, Mario Nicolini, Lorenzo Gianni, Giuseppe Pasini, Francesco Montanari, Davide Tassinari
Journal: Journal of Clinical Oncology (2016)

259 Background: To assess the role of chemotherapy in metastatic, hormone-naïve prostate cancer, we presents the preliminary data of a pooled analysis comparing the outcome of patients with metastatic hormone-naïve prostate cancer. Methods: A pooled analysis of the outcome of randomized clinical trials approaching the role of docetaxel in metastatic hormone-naïve prostate cancer was performed using a random effect model. The final outcome of all the patients enrolled into the trials was the primary end point of our analysis. The pooled final result was reported as pooled Hazard Ratio and 95% Confidence Interval. The between-the trials heterogeneity was assessed using the I 2 test. An α-error of 5% was identified as index of statistical significance. Overall survival of the entire population enrolled into the trials was the outcome of the preliminary analysis, while no subgroup analysis was performed in this preliminary phase of a multi-steps analysis. Results: Three trials (the CHAARTED, the STAMPEDE and the GETUG-AFU 15 trial) were considered eligible and included into the analysis. A pooled Hazard Ratio of 0.76 (95% Confidence Interval of 0.59-0.98, p = 0.037) was detected for overall survival, with an I 2 of 67.8. The pooled datum was obtained observed the outcome of 951 patients treated with docetaxel plus androgen blockade and 1338 with androgen blockade alone. Conclusions: Although the between-the-trials heterogeneity seems to suggest caution in the final interpretation of the results, a significant reduction of the risk of death can be obtained with docetaxel in the treatment of metastatic hormone-naïve prostate cancer. Our preliminary analysis, including all the patients with metastatic hormone-naïve prostate cancer, seems to suggest a role of docetaxel in all the patients with metastatic disease; further data are probably needed to detect its role in some different subclasses of patients (patients with high burden of the disease, fit or unfit patients, elderly patients).
Removal of all ovarian tissue versus conserving ovarian tissue at time of hysterectomy in premenopausal patients with benign disease: study using routine data and data linkage
Authors: Jemma Mytton, Felicity Evison, Peter J Chilton, Richard J Lilford
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To conduct a nationwide study of associations between removal of all ovarian tissue versus conservation of at least one ovary at the time of hysterectomy and important health outcomes (ischaemic heart disease, cancer, and all cause mortality). <b>Study design and setting</b>&nbsp;Retrospective analysis of the English Hospital Episode Statistics database linked to national registers of deprivation indices and of deaths. <b>Participants</b>&nbsp;113 679 patients aged 35-45 who had had a hysterectomy for benign conditions between April 2004 and March 2014. <b>Exposures</b>&nbsp;Bilateral ovarian removal versus no removal or unilateral ovarian removal (ovarian conservation). <b>Main outcome measures</b>&nbsp;Hospital admissions for ischaemic heart disease, cancer, or attempted suicide; deaths, overall and from heart disease, cancer, or suicide. Statistical adjustments were made using Cox regression and propensity score matching for potential confounders. <b>Results</b>&nbsp;A third of patients had bilateral ovarian removal. Patients in the ovarian conservation group were less likely to be admitted for ischaemic heart disease after hysterectomy than were those in the bilateral removal group (adjusted hazard ratio 0.85, 95% confidence interval 0.77 to 0.93; P=0.001). They were also less likely to have a cancer related post-hysterectomy admission (adjusted hazard ratio 0.83, 0.78 to 0.89; P&lt;0.001). A significant difference in all cause mortality was also seen: 0.60% (456/76 581) of patients with ovarian conservation compared with 1.01% (376/37 098) of patients with bilateral removal. Again, this difference in favour of ovarian conservation was significant (adjusted hazard ratio 0.64, 0.55 to 0.73; P&lt;0.001). Fewer deaths related specifically to heart disease (adjusted hazard ratio 0.50, 0.28 to 0.90; P=0.02) and to cancer (0.54, 0.45 to 0.65; P&lt;0.001) occurred in the ovarian conservation group than in the bilateral removal group. No significant difference between groups was found relating to suicide (attempted or completed). The results after propensity score matching were essentially unchanged. <b>Conclusion</b>&nbsp;Patients who had ovarian conservation had a significantly lower hazard of all cause mortality compared with those who had bilateral ovarian removal and also had lower death rates from ischaemic heart disease and cancer. Consistent with this observation, admissions to hospital for both ischaemic heart disease and cancer were also lower in the ovarian conservation group than in the bilateral removal group. Although removal of both ovaries protects against subsequent development of ovarian cancer, premenopausal women should be advised that this benefit comes at the cost of an increased risk of cardiovascular disease and of other (more prevalent) cancers and higher overall mortality.
8-Chloro-Adenosine Inhibits Molecular Poor-Risk Acute Myeloid Leukemia (AML) and Leukemic Stem Cells (LSC) Growth Via Novel RNA- and ATP-Directed Mechanisms: A Novel Therapeutic Approach for AML
Authors: Ralf Buettner, Ching-Cheng Chen, Bijender Kumar, Lisa S Chen, Krister Wennerberg, Ryan Thompson, Tea Pemovska, Ling Li, Varsha Gandhi, Guido Marcucci, Vinod Pullarkat, Steven T. Rosen
Journal: Blood (2015)
Gvhd, Hematopoietic Dysfunction, and Post-Transplant Immune Deficiency: Loss of Marrow Function Leads to Ineffective Extramedullary Hematopoiesis, However Lymphoid Reconstitution Is Restored by the Synergistic Effects of KGF, Sex Steroid Ablation, and Precursor T Cell Adoptive Therapy.
Authors: Jarrod A Dudakov, Alan M. Hanash, Uttam K. Rao, Amanda M. Holland, Robert Jenq, Gabrielle L. Goldberg, Richard Boyd, Marcel R.M. van den Brink
Journal: Blood (2010)
Phase I dose escalation (esc) trial of weekly intravenous (i.v.) BI 836845 in Japanese patients (pts) with advanced solid tumors
Authors: T. Doi, K. Shitara, Y. Naito, Y. Kuboki, T. Kojima, A. Hosono, T. Yoshino, H. Kawamoto, Y. Tadayasu, H. Ugai, Y. Takeuchi, T. Bogenrieder, K. Yoh
Journal: Annals of Oncology (2016)
Slow natural history predicts higher response rate to nivolumab and pembrolizumab in advanced melanoma patients
Authors: N. Kramkimel, V. Heidelberger, O. Huillard, P. Boudou Rouquette, J. Chanal, N. Franck, J. Arrondeau, J. Alexandre, B. Blanchet, J. Mullaert, S. Aractingi, N. Dupin, F. Goldwasser
Journal: Annals of Oncology (2016)
Homodimerization attenuates the anti-inflammatory activity of interleukin-37
Authors: Andrew M. Ellisdon, Claudia A. Nold-Petry, Laura D’Andrea, Steven X. Cho, Jason C. Lao, Ina Rudloff, Devi Ngo, Camden Y. Lo, Tatiana P. Soares da Costa, Matthew A. Perugini, Paul J. Conroy, James C. Whisstock, Marcel F. Nold
Journal: Science Immunology (2017)

Dysregulation of the inflammatory response underlies numerous diseases. Although most interleukin-1 family cytokines are proinflammatory, human interleukin-37 (IL-37) is a powerful, broad-spectrum inhibitor of inflammation and immunity. We determined the crystal structure of IL-37 to establish the anti-inflammatory mechanism of this key cytokine in view of developing IL-37-based therapies. We found that two β-trefoil fold IL-37 molecules form a head-to-head dimer that is stable in solution. IL-37 variants mutated to convert the cytokine into an obligate monomer were up to 13-fold more effective than the dimer in suppressing proinflammatory events both in primary human blood cells and in vivo in murine endotoxic shock. Therapeutic exploitation of the powerful anti-inflammatory properties of monomeric IL-37 may prove beneficial in treating a wide range of inflammatory and autoimmune disorders.
The effects of dexamethasone and placebo on symptom clusters in advanced cancer patients: A preliminary report.
Authors: Sriram Yennu, Janet L. Williams, Gary B. Chisholm, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

187 Background: Advanced cancer patients frequently experience debilitating symptoms that occur in clusters, but few pharmacological studies have targeted symptom clusters. Our objective was to examine the effects of dexamethasone on symptom clusters. Methods: Secondary analysis of a recent RCT of dexamethasone (DEX) vs placebo (PL) on cancer symptoms as assessed by FACIT-F-Fatigue; FAACT-Anorexia-Cachexia; BPI - Pain; HADS- Anxiety-Depression; ESAS: Sleep, Drowsiness, Dyspnea. Symptom clusters were identified based on baseline symptoms [ESAS] using principal component analysis. Cluster scores were computed by adding each scale divided by the maximum value for the scale: Fatigue- Anorexia-Depression = (Fatigue /52 + Anorexia/48+ HADS-Depression/21); Sleep-Anxiety-Drowsiness = (Sleep/10+HADS-Anxiety/21+Drowsiness /10); Pain-Dyspnea = (BPI/10 +Dyspnea /10). Higher number indicates better QOL. Correlations and change in the severity of symptom clusters were analyzed. Results: In 114 evaluable patients, 3 clusters accounted for 63% of the total variance at baseline: Fatigue-anorexia/cachexia-depression cluster (FAD); sleep-anxiety-drowsiness cluster (SAD) and Pain-Dyspnea cluster (PD). Median (IQR) improvement in the FAD cluster at Day 15 and Day 8 was significantly higher in the DEX than in the PL group [0.22 (-0.04, 0.45) vs. 0.06 (-.30, .20), P = 0.016)] and [0.15 (-0.84, 0.35) vs-0.095 (-0.35, 0.16), p = 0.017] respectively. There was no significant change observed in SAD and PD after DEX. Median (IQR) scores for FAD and PD of the DEX group at baseline, day 8, and day 15 were 1.42(1.1,1.7),1.71(1.3,2.1),1.78(1.4,2.2); [1.1(0.8,1.4); 1.38(.04,1.6); 1.43(1.3,1.7) respectively and significantly correlated over time at Day 8 (r = 0.76; p &lt; 0.001) Day 15 (r = 0.55;p &lt; 0.001) [FAD]; Day 8 (r = 0.36; p &lt; 0.001) Day 15 (r = 0.45; p &lt; 0.001) [PD]. Conclusions: FAD cluster showed improvement with dexamethasone and consistent correlation overtime, as compared to SAD and PD cluster. These findings suggest that fatigue-anorexia/cachexia- and depression share a common a common pathophysiologic basis. Further studies are needed to investigate this cluster and target anti-inflammatory therapies. Clinical trial information: NCT00489307.
Innovative approaches to establish and characterize primary cultures: an ex vivo 3D system and the zebrafish model
Authors: C. Liverani, F. La Manna, A. Groenewoud, L. Mercatali, G. Van Der Pluijm, F. Pieri, D. Cavaliere, D.V. Alessandro, C. Spadazzi, G. Miserocchi, A. Bongiovanni, F. Recine, N. Riva, D. Amadori, E. Tasciotti, G. Marcantognini, V. Fausti, B.E. Snaar-Jagalska, T. Ibrahim
Journal: Annals of Oncology (2016)
P02.02 A Complete Nation-Based Registration Ensures Equal and Optimal Management of Primary Brain Tumors Patients
Authors: A. Malmstrom, T. Asklund, S. Kinhult, M. Sjögren, S. Hylin, L. Rosenlund, M. Bergqvist, P. Milos, G. Hesselager, R. Henriksson
Journal: Neuro-Oncology (2016)

A Complete Nation-Based Registration Ensures Equal And Optimal Management Of Primary Brain Tumors Patients
Doxycycline attenuates breast cancer related inflammation by decreasing plasma lysophosphatidate concentrations and inhibiting NF-κB activation
Authors: Xiaoyun Tang, Xianyan Wang, Yuan Y. Zhao, Jonathan M. Curtis, David N. Brindley
Journal: Molecular Cancer (2017)

We previously discovered that tetracyclines increase the expression of lipid phosphate phosphatases at the surface of cells. These enzymes degrade circulating lysophosphatidate and therefore doxycycline increases the turnover of plasma lysophosphatidate and decreases its concentration. Extracellular lysophosphatidate signals through six G protein-coupled receptors and it is a potent promoter of tumor growth, metastasis and chemo-resistance. These effects depend partly on the stimulation of inflammation that lysophosphatidate produces. In this work, we used a syngeneic orthotopic mouse model of breast cancer to determine the impact of doxycycline on circulating lysophosphatidate concentrations and tumor growth. Cytokine/chemokine concentrations in tumor tissue and plasma were measured by multiplexing laser bead technology. Leukocyte infiltration in tumors was analyzed by immunohistochemistry. The expression of IL-6 in breast cancer cell lines was determined by RT-PCR. Cell growth was measured in Matrigel™ 3D culture. The effects of doxycycline on NF-κB-dependent signaling were analyzed by Western blotting. Doxycycline decreased plasma lysophosphatidate concentrations, delayed tumor growth and decreased the concentrations of several cytokines/chemokines (IL-1β, IL-6, IL-9, CCL2, CCL11, CXCL1, CXCL2, CXCL9, G-CSF, LIF, VEGF) in the tumor. These results were compatible with the effects of doxycycline in decreasing the numbers of F4/80+ macrophages and CD31+ blood vessel endothelial cells in the tumor. Doxycycline also decreased the lysophosphatidate-induced growth of breast cancer cells in three-dimensional culture. Lysophosphatidate-induced Ki-67 expression was inhibited by doxycycline. NF-κB activity in HEK293 cells transiently expressing a NF-κB-luciferase reporter vectors was also inhibited by doxycycline. Treatment of breast cancer cells with doxycycline also decreased the translocation of NF-κB to the nucleus and the mRNA levels for IL-6 in the presence or absence of lysophosphatidate. These results contribute a new dimension for understanding the anti-inflammatory effects of tetracyclines, which make them potential candidates for adjuvant therapy of cancers and other inflammatory diseases.
Clinical characteristics of lymphomatous form of Adult T cell lymphoma-leukemia in Peru
Authors: P. Pimentel, B. Beltran, D. Flores, G. Ferrel, S. Falcon, L. Vera, A. Figueroa, K. Portugal, V. Bermudez
Journal: Journal of Clinical Oncology (2005)

6728 Background: Adult T cell lymphoma-leukemia (ATLL) is a type of agressive lymphoma associated to HTLV-1. It is endemic in Peru and it has four clinical forms. We analyzed clinical characteristics of patients with lymphomatous form of ATLL in a general hospital. Methods: It’s a retrospective study conducted to evalue 20 patients with lymphomatous form of ATLL from 1997–2003. Diagnosis was confirmed for immunohystochemestry studies and positive ELISA and Western Blot analysis. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Median age was 64 years (40–84), 12/20 (60%) were females; B symptoms ocurred in 11/20 (55%), zubrod >1 in 15/20 (75%), stage: I 1/20 (5%), II 2/20 (10%), III 3 /20 (15%) and IV 14 (70%), lactate dehydrogenase was increased in all patients (100%), hypercalcemia in 16/20 (80%), albumin was decreased in 17/20 (85%). More frecuent extranodal sites were: skin 8/20 (40%), bone 3/20 (15%) and stomach 2/20 (10%). International Prognostic Index was: low-risk 0/20, low-intermediate 1/20 (5%), high -intermediate 12/20 (60%) and high risk 7/20 (35%). 18 patients received chemotherapy: 9 had CHOP chemotherapy, 5 had regimens CHOP like, 2 patients had metrotexate/cyclophosphamide regimen, 1 patient had fludarabine/cyclophosphamide regimen; finally 1 patient had zidovudine/ Interferon regimen. Overall response ocurred in 4/18 (22%) with 2 complete response and 2 parcial response. All responses ocurred with CHOP regimen. Median survival was 9.7 months. Conclusions: Lymphomatous form of ATLL is an agressive entity with short survival. New streategies of treatment are necessary. No significant financial relationships to disclose.
Kunitz 3-Selective but Not Kunitz 2-Selective TFPI Inhibitors Cause Release of Tfpiα from Endothelial Cells: Insights into the Release Mechanism
Authors: Julie A. Peterson, Cecilia Augustsson, Susan A Maroney, Helle Heibroch Petersen, Ida Hilden, Alan Mast, Wes Zwifelhofer
Journal: Blood (2016)
Baby in joint care with local authority to be vaccinated despite mother’s objections
Authors: Clare Dyer
Journal: BMJ (2017)

A High Court judge has given permission for a baby involved in care proceedings to be vaccinated despite his mother’s objections.

Both the London borough of Barnet and the baby’s mother, named only as TL, have joint parental responsibility for the seven month old child, SL, under an interim care order. Barnet has brought proceedings to take him and his three older siblings into care, and a final hearing is due later this year.

The council wants SL to have the haemophilus influenza type B (Hib) vaccine and the pneumococcal conjugate vaccine (PCV). The mother objects, although she has allowed SL to be given other vaccines. SL’s father has not yet been identified.

Mr Justice MacDonald, who heard the …