tbuckley/cabot-search huggingface dataset:
Mechanism for platelet reduction in anti-neuropilin-1 (MNRP1685A)–treated phase I patients.
Authors: W. C. Darbonne, X. Du, P. Dhawan, D. Hartley, J. Tarrant, H. Taylor, G. Cain, L. M. Shih, R. K. Brachmann, Q. Phung, C. D. Weekes, P. LoRusso, A. Patnaik, H. Xiang, V. Ramakrishnan
Journal: Journal of Clinical Oncology (2011)

e13598 Background: Neuropilin-1 (NRP1), a high affinity receptor for members of the VEGF family, is expressed on endothelial cells (EC) and tumor cells, and is involved with maturation and remodeling of blood vessels. In two phase I studies, administration of human anti-NRP1 antibody (Ab) MNRP1685A resulted in transient platelet (PLT) reductions in patients. To determine if these PLT reductions were due to PLT production or consumption, we evaluated the binding of MNRP1685A to human megakaryocyte (MK) progenitor cells and PLTs and the impact of MNRP1685A on MK development and PLT function. Methods: MNRP1685A binding to human hematopoietic stem cells (HSC), cultured MKs and PLTs was assessed by Western blot (WB), mass spectrometry and flow cytometry (FACS). MNRP1685A effects on platelets from healthy donors and patients on study were analyzed by FACS for activation markers CD62P and activated GPIIbIIIa (PAC1) and evaluated by aggregometry. MNRP1685A effects on MK development were evaluated by HALO proliferation assay and expression of CD61/41 maturation markers via FACS. To examine PLT binding to EC, fluorescein-labeled PLTs were incubated with TNF-stimulated human umbilical vein endothelial cells (HUVEC) in the presence of MNRP1685A and HUVEC-associated fluorescence was measured. Results: We demonstrate specific CD32 (FCγR2a)-dependent and independent MNRP1685A binding to human HSC, cultured MKs and PLTs by FACS and WB. There was no effect of MNRP1685A on HSC proliferation or maturation to MK. Exposure of MNRP1685A to human PLTs ex vivo or in vivo (phase 1 patients) result in modest PLT activation via a CD32-dependent mechanism as measured by FACS for CD62P and PAC1, as well as increased PLT aggregation compared to a control Ab. An increase of CD32-dependent binding of PLTs to HUVEC in vitro was observed in the presence of MNRP1685A, but not with a control Ab. Conclusions: MNRP1685A specifically binds to NRP1 on the surface of human PLTs and cells in the MK lineage, induces modest CD32-dependent PLT activation and binding to activated endothelial cells. These properties of MNRP1685A can contribute to PLT consumption and may explain decreases in circulating PLT levels in patients dosed with MNRP1685A in phase I clinical studies.
Examination of 5Ht3 Receptor Antagonists for Cinv Induced by Tc Therapy in Patients with Gynecologic Cancers
Authors: Yukio Sakata, Noriyoshi Takahashi, Masahiko Odagiri, Mison Kin, Hiroaki Utsu, Yoshihiro Nishioka, Tsuyoshi Yamashita
Journal: Annals of Oncology (2014)
ATCT-29INVESTIGATING THE EFFECT OF REIRRADIATION OR SYSTEMIC THERAPY IN PATIENTS WITH GBM AFTER TUMOR PROGRESSION: A SECONDARY ANALYSIS OF THE NRG ONCOLOGY/RTOG 0525
Authors: Wenyin Shi, Molly Bryan, Mark Gilbert, Minesh Mehta, Deborah Blumenthal, Paul Brown, Egils Valeinis, Kirsten Hopkins, Luis Souhami, David Andrews, Tzuk-Shina Tzahala, Steve Howard, Emad Youssef, Nathalie Lessard, James Dignam, Maria Werner-Wasik
Journal: Neuro-Oncology (2015)

BACKGROUND: There is limited evidence regarding which salvage treatment approach may be of most benefit for glioblastoma patients who progress following standard chemo-radiation treatment. METHODS: This secondary analysis of RTOG 0525 investigated the effect of reirradiation or systemic treatment in patients with tumor progression. Survival time was calculated from date of progression. Survival from first progression was estimated and compared between patients receiving neither radiation or systemic therapy, systemic therapy alone, or any radiation treatment. Patient characteristics were compared between groups and the Cox proportional hazards model was used to compare hazard of death controlling for potential confounders. RESULTS: A total of 637 patients who progressed with recorded information on their non-protocol therapy, excluding those who died less than half a month after progression, were analyzed. 267 patients (42%) received neither radiation or systemic treatment at progression. 88 patients (14%) received some form of radiation treatment. 282 patients (44%) received systemic treatment only. Patients who received no treatment had a median survival (MS) of 4.8 months, lower than radiation treatment (11.3 months), or systemic therapy (10.6 months). However, there was no survival difference between patients who received systemic therapy and those who received radiotherapy (p = 0.3808). Cox models, controlling for potential confounders, demonstrate no difference in hazard of death (1.13, 95% CI 0.8-1.5) between treatment arms. Patients receiving neither therapy had a statistically significant increased hazard of death (2.45, 95% CI: 1.9-3.1). CONCLUSIONS: Salvage treatments after GBM tumor progression were highly variable. Patients who received radiation with or without systemic therapy had a similar MS as those receiving systemic therapy only. Either treatment was statistically significantly better than no treatment. However, this may be the result of poorer functional status of untreated patients. SUPPORT: This project was supported by grants U10CA21661, U10CA180868, U10CA180822 and U10CA37422 from the NCI and Merck.
Clinical and Biologic Significance of <i>MYC</i> Genetic Mutations in <i>De Novo</i> Diffuse Large B-cell Lymphoma
Authors: Zijun Y. Xu-Monette, Qipan Deng, Ganiraju C. Manyam, Alexander Tzankov, Ling Li, Yi Xia, Xiao-xiao Wang, Dehui Zou, Carlo Visco, Karen Dybkær, Jun Li, Li Zhang, Han Liang, Santiago Montes-Moreno, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W.L. Choi, J. Han van Krieken, Jooryung Huh, Maurilio Ponzoni, Andrés J.M. Ferreri, Ben M. Parsons, Michael B. Møller, Sa A. Wang, Roberto N. Miranda, Miguel A. Piris, Jane N. Winter, L. Jeffrey Medeiros, Yong Li, Ken H. Young
Journal: Clinical Cancer Research (2016)

Abstract Purpose: MYC is a critical driver oncogene in many cancers, and its deregulation in the forms of translocation and overexpression has been implicated in lymphomagenesis and progression of diffuse large B-cell lymphoma (DLBCL). The MYC mutational profile and its roles in DLBCL are unknown. This study aims to determine the spectrum of MYC mutations in a large group of patients with DLBCL, and to evaluate the clinical significance of MYC mutations in patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy. Experimental Design: We identified MYC mutations in 750 patients with DLBCL using Sanger sequencing and evaluated the prognostic significance in 602 R-CHOP–treated patients. Results: The frequency of MYC mutations was 33.3% at the DNA level (mutations in either the coding sequence or the untranslated regions) and 16.1% at the protein level (nonsynonymous mutations). Most of the nonsynonymous mutations correlated with better survival outcomes; in contrast, T58 and F138 mutations (which were associated with MYC rearrangements), as well as several mutations occurred at the 3′ untranslated region, correlated with significantly worse survival outcomes. However, these mutations occurred infrequently (only in approximately 2% of DLBCL). A germline SNP encoding the Myc-N11S variant (observed in 6.5% of the study cohort) was associated with significantly better patient survival, and resulted in reduced tumorigenecity in mouse xenografts. Conclusions: Various types of MYC gene mutations are present in DLBCL and show different impact on Myc function and clinical outcomes. Unlike MYC gene translocations and overexpression, most MYC gene mutations may not have a role in driving lymphomagenesis. Clin Cancer Res; 22(14); 3593–605. ©2016 AACR.
The Emergence of Zika Virus
Authors: Kathryn B. Anderson, Stephen J. Thomas, Timothy P. Endy
Journal: Annals of Internal Medicine (2016)

Zika virus (ZIKV) is yet another arbovirus that is rapidly emerging on a global scale, on the heels of a chikungunya epidemic in the Americas that began in 2013. A ZIKV epidemic that began in Brazil in 2015 has now spread rapidly to more than 30 countries in the Americas and the Caribbean, infecting more than 2 million inhabitants. This epidemic currently continues unabated. The explosive nature of recent outbreaks and concerning links to Guillain–Barré syndrome and microcephaly are incompletely understood. Also unknown is the relative importance of sexual transmission of ZIKV and asymptomatic ZIKV infections to the overall burden of transmission. The limited understanding of ZIKV presents an enormous challenge for responses to this rapidly emerging threat to human health. This article reviews the existing literature on ZIKV and proposes critical questions for vaccine development and other areas of needed research.
The Functional Attitude and The Predictive Role Of An Unconventional Subset Of T Cells In Clinical Outcome Of Lymphoma Patients: αβ-Double Negative T Cells, Preliminary Data Of a Prospective Study
Authors: Giacoma De Tullio, Carla Minoia, Simona Serratì, Francesca Merchionne, Giacomo Loseto, Angela La Pietra, Antonello Rana, Angela Iacobazzi, Pasquale Iacopino, Attilio Guarini
Journal: Blood (2013)
Plasmodium falciparum STEVOR phosphorylation regulates host erythrocyte deformability enabling malaria parasite transmission
Authors: Bernina Naissant, Florian Dupuy, Yoann Duffier, Audrey Lorthiois, Julien Duez, Judith Scholz, Pierre Buffet, Anais Merckx, Anna Bachmann, Catherine Lavazec
Journal: Blood (2016)
Case 12-1966
Authors: Stanley P. Bohrer, Benjamin Castleman
Journal: New England Journal of Medicine (1966)

Presentation of CaseA sixty-year-old machine-shop foreman entered the hospital because of hematemesis.Since early childhood he had had attacks of bronchial asthma that were treated with epinephrine, aminophylline and a compound of theophylline, ephedrine and phenobarbital (Tedral). Six years before admission epigastric pain and vomiting developed, and a gastrointestinal series revealed a small sliding hiatus hernia and an ulcer crater within the apex of the duodenal cap (Fig. 1). With an ulcer diet and antacid and phénobarbital therapy the symptoms remained quiescent until four months before admission, when pain in the epigastrium recurred, with intermittent vomiting and a sensation . . .
Rauwolfia Use and Breast Cancer: A Case-Control Study&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: J L Stanford, E J Martin, L A Brinton, R N Hoover
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Rauwolfia Use and Breast Cancer: A Case-Control Study Get access Janet L. Stanford, Janet L. Stanford 4 4Address reprint requests to Dr. Stanford, Landow Building, Room 3C06, National Institutes of Health, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth J. Martin, Elizabeth J. Martin Search for other works by this author on: Oxford Academic PubMed Google Scholar Louise A. Brinton, Louise A. Brinton Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert N. Hoover Robert N. Hoover Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 5, May 1986, Pages 817–822, https://doi.org/10.1093/jnci/76.5.817 Published: 01 May 1986 Article history Received: 10 April 1985 Accepted: 19 September 1985 Revision received: 24 September 1985 Published: 01 May 1986
Impact of trebananib plus weekly paclitaxel on overall survival (OS) in patients (pts) with recurrent ovarian cancer and ascites: Results from the phase III TRINOVA-1 study.
Authors: Bradley J. Monk, Andres Poveda, Ignace Vergote, Francesco Raspagliesi, Keiichi Fujiwara, Duk-Soo Bae, Ana Oaknin, Isabelle Ray-Coquard, Diane M. Provencher, Beth Y. Karlan, Catherine Lhommé, Gary Richardson, Dolores Gallardo Rincon, Robert L. Coleman, Arija Brize, Kathy Zhang, Florian D. Vogl, Bruce A. Bach, Amit M. Oza
Journal: Journal of Clinical Oncology (2015)

5503 Background: Trebananib is an antiangiogenic peptibody that inhibits angiopoietin 1 and 2 binding to the Tie2 receptor. TRINOVA-1 showed significantly longer progression-free survival (PFS) in the trebananib arm (Monk et al, Lancet Oncol 2014;15:799). We evaluated OS, including clinically important subgroups, and postprogression PFS (PFS2). Methods: 919 women with recurrent epithelial ovarian cancer (platinum-free interval < 12 mo) were randomized to paclitaxel (P) 80 mg/m2 IV QW (3 wks on/1 wk off) plus either blinded trebananib 15 mg/kg IV QW (T+P) or placebo (P alone). Treatment continued until progression, toxicity or consent withdrawal. PFS was the primary, intent to treat (ITT) OS a key secondary endpoint. Exploratory PFS2 analysis followed the EMA guidance (EMA/CHMP/27994/2008/Rev.1; 13 Dec 2012). Results: After median follow-up of 17.7 mo and 628 OS events, median OS (ITT) was 19.3 mo with T+P vs 18.3 mo with P alone (HR = 0.95, 95% CI, 0.81–1.11; p = 0.55). Prespecified subgroup analysis of OS also evaluated 295 (32%) pts with ascites at baseline. Characteristics did not differ between pts with and without ascites, and pts with ascites randomized to T+P vs P alone. There was a difference in median OS of 2.2 mo between pts with ascites receiving T+P vs P alone (14.5 vs 12.3 mo; HR = 0.72, 95% CI 0.55–0.93; p = 0.011). After on-study progression, 684 (74%) pts received a median of 2 (range, 1–8) additional lines of therapy. Median PFS2 in the T+P arm increased by 1.6 mo (12.5 vs 10.9 mo with P alone; HR = 0.85, 95% CI 0.74–0.98; p = 0.024). Analysis of time to second subsequent therapy confirmed the PFS2 result (median 13.4 vs 11.7 mo with P alone; HR = 0.83, 95% CI, 0.72–0.96; p = 0.012). The incidence of grade ≥ 3 adverse events (AEs) was 60% for T+P vs 56% for P alone. T+P was associated with more AE-related treatment discontinuations (22% vs 8%) and localized edema events (any grade, 59% vs 27%). Conclusions: Despite multiple additional lines of therapy, OS was longer with T+P among pts with ascites but not in the ITT population (no decrement). The initially reported PFS benefit was sustained through next subsequent anticancer therapy, translating into longer PFS2. Clinical trial information: NCT01204749.
A confidential, blinded study of drug pricing to examine buying power effectiveness in community oncology practices
Authors: M. S. Kirchof, U. B. Favret, W. M. Jordan
Journal: Journal of Clinical Oncology (2008)

20703 Background: The primary driver of income that allows community oncology practices to offset the high cost of purchasing drugs, administering care, and managing cancer patients is drug reimbursement. This study examines the differences in oncology practice drug purchasing effectiveness relative to the number of physicians, purchase volume, inventory management system and drug buyer. Methods: A secure and confidential online research engine sent a survey to 5,373 physicians, nurses, practice managers, pharmacists, and drug buyers. One survey response was allowed from each practice. Pricing data was collected and analyzed over a four week period for Aloxi 0.25mg, Aranesp 200mcg, Avastin 400mg, Camptosar 100mg, Herceptin 440mg, Neulasta 6mg, Neupogen 480mcg, Procrit 40,000u, Rituxan 500mg, and Vectibix 400mg. Partial responses were included in the data set. Results: 159 practices responded to the study. 54 practices submitted complete pricing information on all drugs and 34 practices answered all study questions. The data set revealed practices under 3 physicians (N=87) vs. >3 physicians (N=62), practices buying less than $5M/yr (N=40) vs. >$5M/yr (N=81), and practices using a Pyxis or Lynx inventory management system (IMS) (N=112) vs. No IMS (N=40), pay a higher average price for 7/10 drugs studied. Nurses (N=66) were the most effective buyers receiving the lowest price available on 6/10 drugs and physicians (N=12) were the least effective buyers on 10/10 drugs analyzed. Conclusions: The study response rate and tendencies demonstrate the need for more research and greater visibility into trends and best practices for effective drug buying by community oncology practices. No significant financial relationships to disclose.
Forced silence: a neglected dimension of trauma
Authors: E D Lister
Journal: American Journal of Psychiatry (1982)

The author describes one specific facet of the psychological trauma attendant upon physical violence - the implications of the victim's forced silence about the event. This prohibition of communication, enforced by some implicit or explicit threat, constitutes a secondary trauma of enormous import and has been ignored in the literature. Exploration of this concept can sensitize therapists and point the way toward empathetic and effective intervention.
Regulated selection of germinal-center cells into the memory B cell compartment
Authors: Ryo Shinnakasu, Takeshi Inoue, Kohei Kometani, Saya Moriyama, Yu Adachi, Manabu Nakayama, Yoshimasa Takahashi, Hidehiro Fukuyama, Takaharu Okada, Tomohiro Kurosaki
Journal: Nature Immunology (2016)
Tumour CD274 (PD-L1) expression and T cells in colorectal cancer
Authors: Yohei Masugi, Reiko Nishihara, Juhong Yang, Kosuke Mima, Annacarolina da Silva, Yan Shi, Kentaro Inamura, Yin Cao, Mingyang Song, Jonathan A Nowak, Xiaoyun Liao, Katsuhiko Nosho, Andrew T Chan, Marios Giannakis, Adam J Bass, F Stephen Hodi, Gordon J Freeman, Scott Rodig, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
Journal: Gut (2016)

<h3>Objective</h3> Evidence suggests that CD274 (programmed death-ligand 1, B7-H1) immune checkpoint ligand repress antitumour immunity through its interaction with the PDCD1 (programmed cell death 1, PD-1) receptor of T lymphocytes in various tumours. We hypothesised that tumour CD274 expression levels might be inversely associated with T-cell densities in colorectal carcinoma tissue. <h3>Design</h3> We evaluated tumour CD274 expression by immunohistochemistry in 823 rectal and colon cancer cases within the Nurses9 Health Study and Health Professionals Follow-up Study. We conducted multivariable ordinal logistic regression analyses to examine the association of tumour CD274 expression with CD3<sup>+</sup>, CD8<sup>+</sup>, CD45RO (PTPRC)<sup>+</sup> or FOXP3<sup>+</sup> cell density in tumour tissue, controlling for potential confounders including tumour status of microsatellite instability (MSI), CpG island methylator phenotype, long interspersed nucleotide element-1 methylation level and <i>KRAS</i>, <i>BRAF</i> and <i>PIK3CA</i> mutations. <h3>Results</h3> CD274 expression in tumour cells or stromal cells (including immune cells) was detected in 731 (89%) or 44 (5%) cases, respectively. Tumour CD274 expression level correlated inversely with FOXP3<sup>+</sup> cell density in colorectal cancer tissue (outcome) (p<sub>trend</sub>=0.0002). For a unit increase in outcome quartile categories, multivariable OR in the highest (vs lowest) CD274 expression score was 0.22 (95% CI 0.10 to 0.47). Tumour CD274 expression was inversely associated with MSI-high status (p=0.001). CD274 expression was not significantly associated with CD3<sup>+</sup>, CD8<sup>+</sup> or CD45RO<sup>+</sup> cell density, pathological lymphocytic reactions or patient survival prognosis. <h3>Conclusions</h3> Tumour CD274 expression is inversely associated with FOXP3<sup>+</sup> cell density in colorectal cancer tissue, suggesting a possible influence of CD274-expressing carcinoma cells on regulatory T cells in the tumour microenvironment.
Case 2-1980
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Leslie W. Ottinger, James J. Galdabini
Journal: New England Journal of Medicine (1980)

Presentation of CaseA 56-year-old woman was admitted to the hospital because of fever and diarrhea.She was well until 10 days earlier, when dysuria occurred, and a physician prescribed sulfisoxazole. Two days later she became nauseated and vomited; watery diarrhea and intermittent diffuse abdominal pain occurred. Five days before admission chills and fever developed. An x-ray film of the chest appeared normal. A film of the abdomen disclosed a few slightly dilated loops of small intestine in the left lower quadrant and pelvis; extensive calcification was seen in the aorta and iliac arteries. Deodorized tincture of opium was prescribed, . . .
Tool-like receptor expression in osteosarcoma and neuroblastoma.
Authors: Z. J. Wang, K. Zhang, F. Yu
Journal: Journal of Clinical Oncology (2010)

e20006 Background: Toll-like receptors (TLRs) are major components of the innate immune system, recognizing pathogen-associated molecular patterns found in the large groups of pathogens. A total of 11 TLRs have now been described in humans. Recent studies suggest that TLRs are expressed in a variety of cancer cells. However, the expression pattern in pediatric cancers is largely unknown, and the clear role of TLRs in carcinogenesis or response to chemotherapy remains to be elucidated. Methods: In this study, RT-PCR and Western blot were used to examine the expression of TLR-2, 3, 4, 5, 7 & 9 in 4 osteosarcoma and 3 neuroblastoma cell lines. Results: TLRs mRNAs were detected in all cell lines examined when RT-PCR was used, however, the TLR protein levels were more heterogeneous. While TLR 3 & 4 were homogeneously detected in all cell lines examined, the expression of other TLRs were more selective. Among the 4 osteosarcoma and 3 neuroblastoma cell lines tested, TLR-3 was expressed in 1 osteosarcoma cell lines (U2OS) and 1 neuroblastoma cell lines (SK-N-SH). TLR-5 and TLR-9 expressions were detected in only SK-N-SH, while TLR-7 was present in the other two neuroblastoma cell lines, SK-N-BE and SH-SY5Y. Compared to SK-N-SH, interestingly, significant decrease in TLR- 3 expression was observed in SK-N-SHdox, a doxorubicin-resistant derivative from SK-N-SH following its long term culture in the presence of increasing concentrations of doxorubicin. SK-N-SH and SK-N-SHdox cell lines were then used to determine the effect of poly I:C on cell survival and cisplatin cytotoxicity by MTT assay. No cytotoxicity was observed when both cell lines were treated with poly I:C alone, and no increase in cisplatin cytotoxicity was observed when poly I:C was combined with cisplatin. Interestingly, increased cell survival was observed in SK-N-SHdox but not SK-N-SH when the cells were treated with Poly I:C, suggesting the possible anti-apoptotic/stimulatory effect of Poly I:C. Conclusions: In summary, expression of most TLRs is heterogeneous in osteosarcoma and neuroblastoma cell lines except for TLR-2 and TLR-4, which are expressed in all cell lines examined. Further investigation is warranted to elucidate this intriguing selectivity. No significant financial relationships to disclose.
Prognostic Value of Circulating Exosomal microRNAs in 112 Patients with Multiple Myeloma
Authors: Salomon Manier, Herve Avet-Loiseau, Federico Campigotto, Siobhan Glavey, Karma Salem, Daisy Huynh, Erica N Boswell, Antonio Sacco, Yuji Mishima, Michele Moschetta, Michaela R. Reagan, Yawara Kawano, Kenneth C. Anderson, Aldo M Roccaro, Philippe Moreau, Thierry Facon, Xavier Leleu, Edie A. Weller, Irene M. Ghobrial
Journal: Blood (2014)