tbuckley/cabot-search huggingface dataset:
Bendamustine and lenalidomide in relapsed/refractory lymphoid malignancies.
Authors: B. D. Cheson, C. S. Ujjani, S. M. Karim, T. Goswami, J. Crawford, E. A. Gehan
Journal: Journal of Clinical Oncology (2011)

8066 Background: Front-line therapy for B-cell NHL incorporates chemotherapy and Rituximab (R). Unfortunately, pts often relapse. Bendamustine (B) and Lenalidomide (L) each have efficacy in lymphoma, but their combination has yet to be studied. In this 2-stage phase I study, we proposed combining BL in relapsed/refractory lymphoid malignancies (Stage I) in order to determine the MTD of L for future combination of BLR in B-cell NHL (Stage II). Methods: Pts with relapsed/refractory NHL or Hodgkin lymphoma (HL) with adequate performance status and organ function were eligible. This phase I study utilized a 3 + 3 dose-escalation design. In Stage I pts received B 90 mg/m2 IV on D1, 2 with escalating doses of L (5, 10, 15, 20 mg) po daily of each 28-day cycle. Pts received 6 cycles of BL followed by 6 cycles of L as long as tolerated or until progressive disease (PD). As many pts were noted to have PD, an unplanned interim analysis of Stage I was done. Safety is under evaluation by the DSMB. Results: Of the 7 pts on study, the median age was 52 years, 43% were male, and all were Ann Arbor Stage III/IV. Histologies included DLBCL (3), HL (2), follicular with transformation (1), and cutaneous T-cell (1). An MTD has not yet been reached for L. The second pt enrolled had a DLT of grade 3 rash. Thus, the third pt started at a lower dose of 5 mg every other day. As rash is common with L, the protocol was subsequently amended so that L was given only 21 days of each cycle. In addition, only grade 4 rash or grade 3 rash that did not resolve to < grade 2 within 10 days despite steroids were to be considered DLTs. After these amendments, the trial was reset and 3 new pts were enrolled into Cohort 1 at L 5 mg daily. The first pt in this cohort died during cycle 1 due to PD and was replaced by a fourth. No further DLTs or grade 3/4 rash were noted. Common grade 3/4 toxicities were anemia (57%), leucopenia (57%), and neutropenia (43%). Six of the 7 pts had PD on BL. One pt (DLBCL) had a CR by 2 months and went to transplant. Pts completed a median of 2 cycles of therapy. Most pts withdrew for PD. Conclusions: BL appears to be tolerable in relapsed/refractory lymphoma. Preliminary data suggests limited efficacy but further evaluation is necessary. Additional pts are being accrued to determine the MTD of L prior to adding R in B-cell NHL.
Reduction in the need of inhaled corticosteroids in children with astmha recieving allergen specific immunotherapy
Authors: Carlos Macouzet-Sanchez, Sandra González-Díaz, Alfredo Arias Cruz, Alejandra Macias-Weinmann, Jose Antonio Buenfil-Lopez, Alma Belen Partida-Ortega, Olga Patricia Monge-Ortega, Lissette Ramos-Valencia, Jesus Arturo Ibarra-Chavez
Journal: Journal of Allergy and Clinical Immunology (2017)
Perception of oral corticosteroid side effects in patients with corticosteroid-dependent asthma
Authors: Charlene M. Prazma, Sally E. Wenzel, Linda M. Nelsen, Necdet B. Gunsoy, Sarah M. Cockle, Frank C. Albers, Hector Ortega, Steven W. Yancey
Journal: Journal of Allergy and Clinical Immunology (2017)
Ptdglc-Enriched Lipid Rafts Are a Novel Platform for Apoptosis Signaling in Human Neutrophilic Lineage Cells
Authors: Roudy Chiminch Ekyalongo, Noriko Yokoyama, Hitoshi Nakayama, Hideoki Ogawa, Yoko Tabe, Kenji Takamori, Yoshio Hirabayashi, Kazuhisa Iwabuchi
Journal: Blood (2015)
Hospice Access for Undocumented Immigrants
Authors: Nathan A. Gray, Nathan A. Boucher, Maragatha Kuchibhatla, Kimberly S. Johnson
Journal: JAMA Internal Medicine (2017)

Lilia Cervantes, MD; Stacy Fischer, MD; Nancy Berlinger, PhD; Maria Zabalaga, BA; Claudia Camacho, BA; Stuart Linas, MD; Debora Ortega, PhD
Phase I study of roniciclib (BAY1000394), an oral CDK inhibitor in Japanese patients with advanced solid tumors
Authors: Takashi Seto, Kaname Nosaki, Gen Shinoda, Kensei Hashizume, Iku Yamaguchi, Jun Tsuburaya, Hendrik Nogai, Kohei Shitara, Kiyotaka Yoh
Journal: Annals of Oncology (2016)
Limited efficacy and significant toxicities of lapatinib (Lap) plus chemotherapy as neoadjuvant therapy (NAC) for HER2-positive inflammatory breast cancer (IBC) patients (Pts).
Authors: Ricardo H. Alvarez, Massimo Cristofanilli, Joe Ensor, Anthony Lucci, Wei Tse Yang, Huong T. Le-Petross, James M. Reuben, Gildy Babiera, Lei Huo, Yun Gong, Wendy A. Woodward, Charla A. Parker, Jie S. Willey, Thomas A. Buchholz, Naoto T. Ueno, Vicente Valero
Journal: Journal of Clinical Oncology (2012)

594 Background: IBC is a rare disease but the most aggressive form of locally advanced breast cancer with a higher frequency of HER2 neu amplification (HER2+) compared to non-IBC. The EGFR pathways are also important therapeutic targets in IBC. (Zhang D, 2009). Lap is an oral reversible dual kinase inhibitor of epidermal growth factor receptor of EGFR and HER2. Our objective was to determine the efficacy of Lap in combination with paclitaxel as NAC in pts with previously untreated HER2+ IBC. The primary end-point was to determine the rate of pathological complete response (pCR) defined as no residual invasive disease in the breast and the axillary lymph nodes or Residual Cancer Burden (RCB) of 0. (Symmans FW, 2008). The second endpoint was to assess general safety and cardiac toxicity of this combination therapy. Methods: From October 2008 to May 2011, 15 chemo-naïve pts were treated with Lap 1,250 mg/day as a single agent for 2 weeks, followed by 12 weeks of paclitaxel (80 mg/m 2 weekly) plus Lap (1,000 mg/day), and finally with 4 cycles of FEC-75 mg/m 2 regimen plus Lap (1,000 mg/day) before surgery. Among 12 first pts enrolled, 6 pts had grade 3 diarrhea (CTCAC v3.0) and the protocol was amended to reduce the Lap dose to 750 mg/day. After modified radical mastectomy (MRM), patients received radiation therapy and one year of adjuvant trastuzumab. Results: Median age was 53.8 (range, 39 -70), performance status was 0 (13 pts), 1 (2 pts), 4 pts had metastatic disease at diagnosis. 10 of 15 pts had MRM. One pt achieved pCR. Five pts did not complete the NAC due to grade 2 cardiomyopathy (1), liver dysfunction (2), diarrhea (1), and insurance denial after pt started treatment (1). The trial was stopped early due to severe toxicity (&gt;15%) and lack of efficacy. Conclusions: Lap in combination with chemotherapy as NAC has a limited anti-tumor activity in pts with HER2+ IBC with a pCR rate of 6.6%. Lap and paclitaxel was associated with severe diarrhea toxicity and required multiple dose reductions of Lap. With the recent promising results in HER2+ NAC studies, the role of Lap should continue to be explored in combination with other anti-HER2 agents in IBC patients.
Expanded CLL CD8+ T-Cells Are Driven Into a Senescent KLRG1+ Effector Memory Phenotype
Authors: Joachim Rudolf Göthert, Lewin Eisele, Ludger Klein-Hitpass, Stefanie Weber, Anja Führer, Ludger Sellmann, Alexander Roeth, Ulrich Duehrsen, Hanspeter Pircher, Jan Dürig
Journal: Blood (2010)
Prognosis of Adult Patients ≤60 Years with AML and Aberrations of Chromosome 11q23: Pooled Data Analysis of the AML-SG and SHG-Dresden Study Groups.
Authors: Jürgen Krauter, Irina Schäfer, Anke Kohlenberg, Katharina Wagner, Gerhard Heil, Markus Schaich, Gerhard Ehninger, Konstanze Döhner, Hartmut Döhner, Richard Schlenk, Arnold Ganser
Journal: Blood (2005)
STUDIES ON THE BACTERIOPHAGE OF D'HERELLE
Authors: Ralph S. Muckenfuss
Journal: The Journal of Experimental Medicine (1928)

1. Each bacteriophage is a specific antigen. 2. The antibodies against the bacteriophage are independent of those against the bacterial substrate used in preparing the phage. 3. The reaction of neutralization is closely analogous to that of the neutralization of toxin by antitoxin. 4. The serum of mice experimentally infected with mouse typhoid (M.T.) did not become capable of neutralizing phages acting on the infecting organism. 5. The use of the reaction of neutralization of bacteriophage in the diagnosis of disease as proposed by Sonnenschein seems impractical.
Rac GTPases Are Potential Therapeutic Targets in p210-BCR-ABL-Induced Myeloproliferative Disease (MPD).
Authors: Emily K. Thomas, Jose A. Cancelas, Heedon Chae, Adrienne D. Cox, Patricia J. Keller, Danilo Perrotti, Paolo Neviani, Brian J. Druker, Yi Zheng, Chad E. Harris, David A. Williams
Journal: Blood (2007)
Use of MTHFR A1298C polymorphism to predict response in a phase II international clinical trial of patients with advanced gastric (GC) or gastroesophageal junction (GEJ) adenocarcinoma treated with first-line lapatinib plus capecitabine.
Authors: M. J. Labonte, D. Yang, W. Zhang, P. M. Wilson, A. Gerger, P. O. Bohanes, Y. Ning, L. Benhaim, R. El-Khoueiry, Y. M. Nagarwala, A. M. Kemner, M. J. Pishvaian, R. K. Hsieh, O. Gladkov, S. Urba, S. Y. Rha, D. Sakaeva, S. Iqbal, A. B. El-Khoueiry, H. Lenz
Journal: Journal of Clinical Oncology (2011)

4076 Background: The international, phase II clinical trial, LPT109747, demonstrated that lapatinib (1250mg/d, continuous) plus capecitabine (100mg/m2 BID, 14 of 21 days) had efficacy and was well tolerated as first-line treatment for advanced GC or GEJ adenocarcinoma. HER2 overexpression was not required at study entry. The response rate (RR) was 22.4% (17.9% confirmed). The present study aimed to identify germline single nucleotide polymorphisms (SNPs) in genes involved in 5-FU metabolism (TYMS and MTHFR) and HER signaling (EGF, EGFR, HER2, VEGF, IL8, COX-2, CCND1) to identify pts that may benefit from this regimen. Methods: 67 pts were included, with a median age 61 y (range: 22-89 y); 75% GC, 25% GEJ. The median progression-free survival (PFS) and overall survival (OS) were 14.3 wks (95% CI:12.3, 18.9) and 27.6 wks (95% CI:22.1, 40.6), respectively. For the current study, whole blood was available for DNA extraction from 56 pts. There were no differences in baseline pts characteristics, RR and PFS between the pts included in the analysis and the entire study population. Intratumoral HER2 mRNA levels was assessed using laser capture microdissection and quantitative real-time PCR. SNPs were evaluated using PCR-based protocols, and the associations with RR and PFS were analyzed using Fisher’s exact test, Kaplan-Meier curves, and log-rank tests as appropriate. Results: There was a statistically significant association between the MTHFR A1298C SNP rs1801131 and RR (p=0.0399). Pts carrying the AA genotype were more likely to respond to treatment (47.6%) compared with pts with either the AC or CC genotype (13.3%). No significant associations between other SNPs and RR or PFS were observed. Although not significant, high HER2 mRNA expression (>0.07, n=10) before treatment was associated with shorter PFS compared to low HER2 mRNA expression (<0.07, n=9; p=0.098). Conclusions: Although exploratory, this study suggests that MTHFR A1298C may be useful in predicting clinical outcome in metastatic GC pts treated with lapatinib plus capecitabine.
How should we pay for the NHS?
Authors: Fiona Godlee
Journal: BMJ (2017)

The question of how much we should spend on the NHS, and by what means, seems to have reached new urgency. Over the past week the BBC’s NHS Health Check series of special reports has given graphic form to a rising tide of concern, as waiting lists lengthen, increasingly sick and elderly patients queue inside and outside emergency departments, and overburdened doctors and nurses speak openly about their fears for patients’ safety. Patients and relatives are asked what’s to be done. Their …
CBIO-09. ACID CERAMIDASE CONFERS RADIORESISTANCE TO GLIOBLASTOMA CELLS
Authors: Ninh B. Doan, Mona M. Al-Gizawiy, Ha Son Nguyen, Kathleen M. Schmainda, Wade M. Mueller, Shama P. Mirza
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM) remains the most common malignant cancer of the central nervous system. Therapeutically resistant GBM or glioblastoma stem-like cells (GSC) are hypothesized to cause inevitable recurrence. Acid ceramidase (ASAH1), a lysosome cysteine amidase important in the metabolism of sphingolipids, plays a significant role in tumor progression in many cancers. Here, the role of acid ceramidase in promoting radioresistant GBM was evaluated. Acid ceramidase levels were measured by Western blot. Liquid chromatography mass spectroscopy technique was utilized to measure sphingolipid levels. MTT assays were used to calculate cell survivals. Adult U87 and pediatric SJGBM2 GBM cell lines that survived 10 gy of radiation had significantly higher expression levels of ASAH1. Clinically, these irradiated cells would be an equivalent to that of recurrent GBM that occurred in patients who have undergone radiation treatment. Similarly, irradiated patient GBM tissues expressed a much higher level of ASAH1 compared to the pre-radiation tissue from the same patient. Consistent with previous data, irradiated cells also expressed a higher level of CD133, suggesting a possibility that GSCs are the cells that survived radiation and expressed a high level of ASAH1. Irradiated cells also secreted more ASAH1 into the media than non-irradiated cells. Media containing a high level of secreted ASAH1 promoted 50% more cell growth in U87 cells vs. media containing a lower level of secreted ASAH1. More therapeutically relevant is that these irradiated cells had their cell growth decreased by 50% when treated with ASAH1 antibody, further emphasizing the importance of ASAH1 in treating recurrent or radioresistent GBM. Irradiated U87 cells carry a lower concentration of ceramide and a higher amount sphingosine than native U87 cells. These data suggest that acid ceramidase confers radioresistance to GBM cells by altering the sphingolipid metabolism pathway, making it a valuable drug target.
Elevated Leukocyte Alkaline Phosphatase Scores Induced by Jak2 V617F Mutation
Authors: Seido Oku, Katsuto Takenaka, Takashi Kumano, Takuro Kuriyama, Shingo Urata, Kotaro Shide, Haruko Shimoda, Hiromi Iwasaki, Toshihiro Miyamoto, Takanori Teshima, Koji Nagafuji, Kazuya Shimoda, Koichi Akashi
Journal: Blood (2008)
A Population Study Of Sensitisation And Allergy To Relevant Inhaled And Food Allergens In A Mediterranean Region
Authors: Natalia I. Perez-Sanchez, Natalia Blanca-Lopez, Laura Victorio, J Damian Lopez, Francisco Feo-Brito, Mayte Villalba, Miguel Blanca, Francisco Monteseirin, Gabriela Canto, Jose Antonio Cornejo
Journal: Journal of Allergy and Clinical Immunology (2017)
449PD Relative abundance of EGFR mutations predict tumor metastasis and EGFR-TKIs prognosis in patients with nonsmall cell lung cancer
Authors: H. Zhen, Q. Wang, H. Wang, H. Tang, Z. Zhang, Y. Wu, L. Wang, D. Zhao, L. Yang, B. Wei, J. Ma, Y. Guo
Journal: Annals of Oncology (2016)
Effect of a gene expression-based tissue of origin test's impact on patient management for difficult-to-diagnose primary cancers.
Authors: J. C. Hornberger, M. Amin, G. R. Varadhachary, W. D. Henner, J. S. Nystrom
Journal: Journal of Clinical Oncology (2011)

459 Background: An important step for a novel test is assessing its clinical utility and real-world effect on diagnosis and patient management. This report describes the results of a survey of physicians who have ordered a gene expression profile assay for identification of tumor tissue of origin (Pathwork Tissue of Origin Test) for patients with difficult-to-diagnose primary cancers. Methods: The IRB-approved registry collects data from participating physicians who have ordered the Tissue of Origin test for their patients. To minimize recall bias, a detailed interview is conducted using both a web-based questionnaire and a confirmatory telephone interview with the physicians. Chart survey includes collection of data on patient demographics, diagnostic procedures including imaging and pathology including immunohistochemistry as well as therapy. The physicians are queried regarding their working diagnoses and treatment recommendations prior to and after Tissue of Origin Test result availability. Results: Enrollment in the registry is ongoing. Fifty-nine patients (34 women) have been studied and 48 participating physicians have completed the interview. Survey results suggest that most patients have undergone extensive evaluation including multiple imaging tests (median, 6) and exhaustive immunohistochemistry (median, 10) prior to gene expression analysis. For these 59 pts, based on clinicopathologic evaluation, physicians reported working diagnoses for 46% of patients prior to test results and 83% after test results. Treatment recommendations were changed for 53% of patients. The majority (70%) of treatment changes were for chemotherapy. Physicians (n=26) reported that the Tissue of Origin test decreased the diagnosis associated anxiety in 62% of patients. Conclusions: This ongoing registry study confirms that in patients with difficult-to-diagnose primary cancers, extensive baseline diagnostics is not uncommon and less than half of the patients have an established working diagnosis. Survey results suggest that the Tissue of Origin Test led to a change in working diagnosis and changed treatment recommendations in over half the patients. [Table: see text]
510P Safety and efficacy of eribulin mesylate in patients with advanced soft tissue sarcoma in daily practice
Authors: C. Inagaki, T. Shimoi, H.S. Okuma, A. Kawachi, A. Shimomura, E. Noguchi, M. Yunokawa, K. Yonemori, C. Shimizu, Y. Fujiwara, K. Tamura
Journal: Annals of Oncology (2016)
332O Co-expression of PD-L1 and p-AKT is associated with poor prognosis in diffuse large B-cell lymphoma via PD-1/PD-L1 axis activating intracellular AKT/mTOR pathway in tumor cells
Authors: H. Zhang, X. Wang, L. Dong, H. Lv, W. Li, Z. Song, L. Li, S. Zhou, L. Qiu, Z. Qian, X. Liu, L. Feng, B. Meng, K. Fu, X. Wang, Q. Pan-Hammarström, P. Wang
Journal: Annals of Oncology (2016)
Unmanipulated Haploidentical Blood and Marrow Transplantation in High Risk Hematologic Malignancies
Authors: Benakli Malek, Ahmed Nacer Redhouane, Bouarab Hanane, Baazizi Mounira, Zerkout Sara, Rahmoune Nadia, Mehdid Farih, Ait Ouali Dina, Belhadj Rachida, Hamladji Rose-Marie
Journal: Blood (2015)
A Phase II of Combination D aunorubicin and Cytarabine (A ra-c) and Nilotinib (TA signa) (DATA) in Patients Newly Diagnosed with Acute Myeloid Leukemia and KIT Expression: Interim Results
Authors: Aref Al-Kali, Raoul Tibes, Jeanne Palmer, Hassan B Alkhateeb, Pamela Atherton, Fei Yan, Shujun Liu, Rong He, Shahrukh K. Hashmi, Mark R Litzow
Journal: Blood (2015)
Effect of Increased Tissue Factor Pathway Inhibitor (TFPI) Levels On Factor Xa Inhibition and Global Hemostasis in the Presence of TFPI-Antagonistic Aptamer BAX 499.
Authors: Michael Dockal, Rudolf Hartmann, Sabine Knappe, Michael Palige, Willibald Kammlander, Klara Kunckova, Hartmut J. Ehrlich, Friedrich Scheiflinger
Journal: Blood (2012)
Survival outcomes in Egyptian patients with triple-negative breast cancer: Single institute experience.
Authors: Mona Kamal Jomaa, Ahmed Aly Nagy
Journal: Journal of Clinical Oncology (2015)

158 Background: Triple-negative breast cancer (TNBC) is a unique subtype and consider as an aggressive disease without established targeted treatment options. This study conducted to determine the incidence, characteristics, and survival outcomes of TNBC patients in an Egyptian cancer institute. Methods: Medical records of 520 patients treated between 2010-2011 in Clinical Oncology Department-Ain Shams University-Egypt were analyzed. Cox proportional hazards models were used to evaluate the association between TNBC and DFS and OS after adjusting for other covariates. Results: Among the 520 patients, 139 were TNBC .The median age was 50 years (SD±11.767, Range 20-80 ) versus 52 years (SD±12.134, Range 20-80), median tumor diameter was 5 cm (SD± 1.408, Range 1-7) versus was 5 cm (SD± 1.401, Range 1-7) , and median number of positive axillary LN was 3 (SD± 4.779, Range 0-37) versus 3 (SD± 4.832, Range 0-25) in non TNBC and TNBC respectively . Median disease-free survival was 24 months (SD± 14.128, Range 1-69 ) versus 15 months (SD± 8.811, Range 1-43 ) and median overall survival was 41 months (SD± 16.249, Range 3-60) versus 31 months (SD± 12.184, Range 7-60 ) in non TNBC and TNBC respectively. About 85.6 % of the TNBC tumors were IDC, 4.4 % were ILC and 5% were mixed. About 1.4 % of the TNBC tumors were grade I, 70.5 % were grade II and 28.1% were grade III. Median disease-free survival was 24 months (95%CI 21.679- 26.321) versus 15 months (95%CI 12.587-17.413) (p&lt; 0.001) and median overall survival was 44 months (95%CI 41.396-46.604) versus 31 months (95%CI 29.460-32.540) (p&lt; 0.001) in non TNBC and TNBC respectively. In TNBC cohort , DFS was 12 months (95%CI 11.464-12.536) in patients with grade III tumors versus 25 months (95%CI 22.359-27.641 )in patients with other grades (p&lt; 0.001), this was also reflected in OS as 29 months (95%CI 25.129-32.871 ) versus 44 months (95%CI 41.238-46.762 ) (p&lt; 0.001). Conclusions: Multivariate analyses supported a conclusion that TNBC subtype was an independent adverse prognostic factor for survival along with other known risk factors such as tumor grade.
A New Link Between Autism and Masculinity
Authors: Larry Cahill
Journal: JAMA Psychiatry (2017)

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DNA Ligase III Alpha and (Poly-ADP) Ribose Polymerase (PARP1) Are Therapeutic Targets in Imatinib-Resistant (IR) Chronic Myeloid Leukemia (CML).
Authors: Lisa A. Tobin, Aaron P. Rapoport, Ivana Gojo, Maria R. Baer, Alan E. Tomkinson, Feyruz V. Rassool
Journal: Blood (2009)
Eph-B2 Receptor Tyrosine Kinase Is Overexpressed in Waldenstrom's Macroglubulinemia and Plays a Major Role in Its Interaction with the Bone Marrow Microenvironment.
Authors: Abdel Kareem Azab, Feda Azab, Aldo M. Roccaro, Antonio Sacco, Phong Quang, Hai T. Ngo, Molly R Melhem, Judith M. Runnels, Patricia Maiso, Irene M. Ghobrial
Journal: Blood (2009)
Hepatic decompensation is the major driver of death in HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma
Authors: Giuseppe Cabibbo, Salvatore Petta, Marco Barbara, Simona Attardo, Laura Bucci, Fabio Farinati, Edoardo G. Giannini, Giulia Negrini, Francesca Ciccarese, Gian Lodovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Franco Borzio, Rodolfo Sacco, Roberto Virdone, Fabio Marra, Andrea Mega, Filomena Morisco, Luisa Benvegnù, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Andrea Olivani, Alberto Masotto, Gerardo Nardone, Antonio Colecchia, Marcello Persico, Antonio Craxì, Franco Trevisani, Calogero Cammà
Journal: Journal of Hepatology (2017)