tbuckley/cabot-search huggingface dataset:
Galectin-1–driven T cell exclusion in the tumor endothelium promotes immunotherapy resistance
Authors: Dhanya K. Nambiar, Todd Aguilera, Hongbin Cao, Shirley Kwok, Christina Kong, Joshua Bloomstein, Zemin Wang, Vangipuram S. Rangan, Dadi Jiang, Rie von Eyben, Rachel Liang, Sonya Agarwal, A. Dimitrios Colevas, Alan Korman, Clint T. Allen, Ravindra Uppaluri, Albert C. Koong, Amato Giaccia, Quynh Thu Le
Journal: Journal of Clinical Investigation (2019)

Immune checkpoint inhibitors (ICIs), although promising, have variable benefit in head and neck cancer (HNC). We noted that tumor galectin-1 (Gal1) levels were inversely correlated with treatment response and survival in patients with HNC who were treated with ICIs. Using multiple HNC mouse models, we show that tumor-secreted Gal1 mediates immune evasion by preventing T cell migration into the tumor. Mechanistically, Gal1 reprograms the tumor endothelium to upregulate cell-surface programmed death ligand 1 (PD-L1) and galectin-9. Using genetic and pharmacological approaches, we show that Gal1 blockade increases intratumoral T cell infiltration, leading to a better response to anti-PD1 therapy with or without radiotherapy. Our study reveals the function of Gal1 in transforming the tumor endothelium into an immune-suppressive barrier and that its inhibition synergizes with ICIs.
Endocrines in Gynaecology
Authors: R. Greene
Journal: BMJ (1947)

winding or writing) and indistinguishable from Osler's digital nodes.A similar complaint is seen in rheumatoid arthritis and in epidemic polyarthritis.' Chronic rheumatic carditis may pre- sent a transient bacteriaemia, splenomegaly, purpura (petechia, subuLngual splinter, and subconjunctival)9 and be confused with septic endocarditis, in 10% of which the blood culture is per- sistently negative."5Both may coexist."' The absolute diagnostic criteria of the latter are organic heart disease plus a persistently positive blood culture (non-specific) or infective emboli.Penicillin therapy would be diagnostic if curative:Chronic persistent rheumatic carditis in an adult has hitherto not been reported, but I have witnessed such a case resulting from the too early mobilization of an acute myocarditis prior to the disappearance of the abnormalities of the E.C.G.For the chronic as for the acute carditis complete bed rest is essen- tial.'0Comparison of the recent cardiac research in idiopathic rheumatoid arthritis with the usual sad course and prognosis of chronic rheumatic carditis demonstrates its validity.Of the 60--700,% iof the bedridden or inactive patients presenting in- flammatory heart disease post mortem less than 25 00 was detected clinically during their illness.'' ' The management of rheumatic fever is still a test of the skill of a physician.-Iam, etc., Dublin.
DNA Methylation Profiling of AML Reveals Epigenetic Subgroups with Distinct Clinical Outcome
Authors: Sebastian Vosberg, Paul Kerbs, Vindi Jurinovic, Klaus H. Metzeler, Susanne Amler, Cristina Sauerland, Dennis Görlich, Wolfgang E. Berdel, Jan Braess, Wolfgang Hiddemann, Karsten Spiekermann, Tobias Herold, Philipp A. Greif
Journal: Blood (2019)
shRNA-Interleukin-6 Modified CD19-Specific Chimeric Antigen Receptor T Cell Significantly Improves the Safety in Acute Lymphoblastic Leukemia
Authors: Liqing Kang, Xiaowen Tang, Nan Xu, Minghao Li, Jingwen Tan, Wei Qi, Zhou Yu, Xiaoyan Lou, Shengli Xue, Xin Li, Jian Zhang, Jia Chen, Zhenkun Wang, Caixia Li, Fu Cheng Cheng, Depei Wu, Lei Yu
Journal: Blood (2019)
Factor VIII Use in the Treatment of Breakthrough Bleeds in Hemophilia A Patients without Inhibitors on Emicizumab Prophylaxis: The Phase 3 HAVEN 3 Study Experience
Authors: Michael Callaghan, Benjamin Trzaskoma, Richard H. Ko, Lucy Lee, Anisha M. Patel, Eunice Tzeng, Michelle Lynn Shah, Tiffany Y. Chang, Markus Niggli, Christophe Dhalluin, Johnny Mahlangu
Journal: Blood (2019)
The Magnitude of Lactate Dehydrogenase Elevation As a Predictive Factor for Central Nervous System Relapse in Diffuse Large B-Cell Lymphoma
Authors: Iolanda Vieira, Miguel Quintela, Cláudia Moreira, Sérgio Chacim, Nelson Domingues, Isabel Oliveira, Ana Espirito Santo, Maria Ilidia Moreira, Ângelo Martins, Maria Luisa Viterbo, Dulcineia Pereira, Jose Mario Mariz
Journal: Blood (2019)
DDIS-06. ANTICANCER EFFECTS OF THE SMALL MOLECULE INHIBITOR SB747651A IN GLIOBLASTOMAS
Authors: Arnon Knudsen, Henning B Boldt, Bjarne Kristensen
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Most glioblastomas harbor several different genetic alterations in major cell signaling pathways, leading to tumor progression and treatment resistance. Single-targeted therapies against these alterations have thus far failed to show major clinical value. The aim of this study was to investigate the anticancer effects of SB747651A, a multi-target small molecule inhibitor, targeting the RAS-MAPK and AKT-PI3K kinases AKT, MSK1/2, RSK1/2 and p70S6K in glioblastomas. METHODS Three patient-derived glioblastoma cultures were grown as free-floating spheroids and treated with 5 or 10 µM SB747651A. Exposed cells were subject to assays investigating cell viability (propidium iodide), apoptosis (Caspase 3/7), spheroid formation capacity, chemo sensitivity (temozolomide), and migration. In vivo studies are currently ongoing. RESULTS Exposed cells showed increased cell death and apoptosis across all three cell cultures in a dose-dependent manner vs. controls (P=0.001). Combination treatment with SB747651A and temozolomide resulted in a significant dose-dependent synergistic effect on cell death in all cell cultures. The fraction of spheroid-initiating cells was significantly reduced in exposed cells (1 in 12 cells) compared to controls (1 in 5 cells; P=0.001), and the growth rate of treated tumor spheroids was reduced by up to 47% (P=0.001). Exposed spheroids showed reduced cell migration in 2 of 3 cell lines, with a maximum reduction of migration distance by 60.4% (P=0.001). CONCLUSION SB747651A treatment has shown promising in vitro results by targeting mechanisms with high relevance for the progression and treatment resistance of glioblastomas. Ongoing in vivo studies are aiming to validate these findings, and to uncover potential use of SB747651A in the clinical setting.
Cytokine-Induced Memory-like (ML) NK Cells Persist for &gt; 2 Months Following Adoptive Transfer into Leukemia Patients with a MHC-Compatible Hematopoietic Cell Transplant (HCT)
Authors: Jennifer A Foltz, Melissa M Berrien-Elliott, Carly Neal, Mark Foster, Ethan McClain, Tim Schappe, Sweta Desai, Michelle Becker-Hapak, Amanda F Cashen, Todd A Fehniger
Journal: Blood (2019)
A Phase 1 Study of Lenzilumab, a humaneered recombinant Anti-Human Granulocyte-Macrophage Colony- Stimulating Factor (anti-hGM-CSF) Antibody, for Chronic Myelomonocytic Leukemia (CMML)
Authors: Mrinal M Patnaik, David A Sallman, Abhishek A Mangaonkar, Rachel Heuer, Jeffery Hirvela, Darci Zblewski, Aref Al-Kali, Deanna Kanne, Rahil Ismail, Rami S. Komrokji, Adrian Lo, Maria E Balasis, Cameron Durrant, Dale Chappell, Omar Ahmed, Alan F. List, Eric Padron
Journal: Blood (2019)
A CK1δ/CK1ε Regulated Metabolic Circuit Is a Therapeutic Vulnerability for Multiple Myeloma
Authors: Karen L Burger, Mark B. Meads, Anders Berglund, Paula S. Oliveira, Allison Distler, Praneeth Reddy Sudalagunta, Timothy Jacobson, Jamie Teer, Eric A. Welsh, Hongyue Dai, John M. Koomen, Alugubelli Raghunandan Reddy, Gabriel De Avila, Alexandre Tungesvik, William Roush, Ariosto Siqueira Silva, Kenneth H. Shain, John Cleveland
Journal: Blood (2019)
Spontaneous Rupture of the Spleen
Authors: J. A. V. Nicoll
Journal: BMJ (1952)

MJoHL 801 the baby was removed from the mother as soon as possible it seems probable that the infection was acquired by contact at birth rather than due to intrauterine transmission.Of particular interest is the myocarditis in the infant.Saphir and Wile (1942) first drew attention to the occurrence of myocarditis in poliomyelitis, but it is by no means constant.Saphir (1945) described myocarditis in 10 of 17 patients examined after death.The second case reported by Baskin et al. showed histological evidence of severe acute and healing myocarditis.The lesions in the heart in the case here reported were widely separated and could not be described as severe, the intervening muscle being normal.The child died from bulbar paralysis and not myocardial failure.dra'matic suddenness or with preliminary malaise, depend- ing on how long the bleeding goes on before the capsule ruptures.In the above case it is likely that the splenic capsule was torn from an engorged spleen by the trivial effort of moving a milk churn.
Ndepth: A Randomized Controlled Trial of a Novel Dose-Prediction Equation to Determine Maximum Tolerated Dose for Hydroxyurea Therapy in Pediatric Patients with Sickle Cell Anemia
Authors: Alex George, Bogdan Dinu, Norma Estrada, Charles Minard, Richard L Hurwitz, Donald Mahoney, Amber M Yates, Mary Vaughan, Alaundra Carmouche, Gladstone Airewele, Kirk E Susan, Titilope Adenike Fasipe, Precious Uwaezuoke, Russell E. Ware
Journal: Blood (2019)
TMIC-63. ENDOCAN BRIDGING THE GAP: TUMOR ENDOTHELIAL CELL SECRETOME AND THE VASCULATURE-PROXIMAL TUMOR EDGE
Authors: Soniya Bastola, Yasmin Ghochani, Marat S Pavlyukov, Sadashib Ghosh, Morgan Kurowsky, Harley Kornblum, Ichiro Nakano
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma (GBM) is a highly invasive, angiogenic and therapeutically resistant primary brain tumor. It is impossible to completely resect the tumor, which subsequently leaves behind tumor “edge” that can act as seeds for recurrence. We recently reported the leading “edge” and tumor core have the presence of two distinct types of glioma stem-like cells (GSCs) that resemble proneural (PN) and mesenchymal (MES) subtypes, respectively. GSCs are enriched in perivascular niches, and vascular endothelial (VE) cells are known to provide paracrine factors, radioresistance properties to GSCs. Therapeutically, targeting GBM using an anti-angiogenic anti-VEGF inhibitor, Bevacizumab, did not aid in overall survival and instead resulted in aggressive MES phenotype. Hence, it is imperative to study this nexus in greater detail to develop novel targeted therapies for VE and GBM cells. The purpose of this study was to understand the molecular mechanisms emanating from VE cells that cause the invading “edge” to recur and determine if targeting these molecular cascades can provide therapeutic benefit. RESULTS Using unbiased approach to identify paracrine factors from GBM patient derived VE cells, we identified endocan, a vascular endothelial cell secreted molecule, as a pro-tumorigenic factor essential for neovascularization, radioresistance, and stemness of GBM edge tumor cells. Utilizing patient-derived and mouse glioblastoma sphere models and the corresponding intracranial tumor models, we demonstrate that endocan maintains the “edge”-located glioma stem cell signature and protects glioblastoma cells from radiation-induced differentiation and apoptosis. Mechanistically, we show that endocan is a novel ligand that interacts with PDGFRa and induce its phosphorylation, leading to phosphorylation of the downstream targets PI3K and MAPK in GBM. CONCLUSIONS Collectively, these findings demonstrate a novel signaling axis of endocan-PDGFRa in GBM that is activated by tumor endothelial cell and plays an essential role in glioma stem cells maintenance and radioresistance in tumor “edge”.
CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives
Authors: Mohamad Mohty, Jordan Gautier, Florent Malard, Mahmoud Aljurf, Ali Bazarbachi, Christian Chabannon, Mohamed A. Kharfan-Dabaja, Bipin N. Savani, He Huang, Saad Kenderian, Arnon Nagler, Miguel-Angel Perales
Journal: Leukemia (2019)
Genome-Wide Association Study Identifies an Immune-Related Etiology for Severe Aplastic Anemia
Authors: Sharon A. Savage, Mathias Viard, Weiyin Zhou, Meredith Yeager, Shengchao Li, Tao Wang, Aurelie Vogt, Belynda Hicks, Laurie Burdett, Charles Chung, Colm O'hUigin, Michael Dean, Kelvin de Andrade, Neal D Freedman, Sonja I Berndt, Nathaniel Rothman, Qing Lan, James R. Cerhan, Susan L Slager, Yawei Zhang, Lauren R Teras, Michael Haagenson, Stephen J Chanock, Stephen R. Spellman, Youjin Wang, Amanda Willis, Medhat Askar, Stephanie J. Lee, Carrington Mary, Shahinaz M Gadalla
Journal: Blood (2019)
Risk-Adapted Starting Age of Screening for Relatives of Patients With Breast Cancer
Authors: Trasias Mukama, Elham Kharazmi, Xing Xu, Kristina Sundquist, Jan Sundquist, Hermann Brenner, Mahdi Fallah
Journal: JAMA Oncology (2019)

<h3>Importance</h3> Breast cancer screening guidelines acknowledge the need for earlier screening for women at increased risk but provide limited guidance for women with a family history of breast cancer. A risk-adapted starting age of screening for relatives of patients with breast cancer may help supplement current screening guidelines. <h3>Objective</h3> To identify the risk-adapted starting age of breast cancer screening on the basis of a woman's detailed family history. <h3>Design, Setting, and Participants</h3> This nationwide cohort study analyzed data recorded in the Swedish family-cancer data sets. All women born from 1932 onward and with at least 1 known first-degree relative (FDR) were included (N = 5 099 172). Data from January 1, 1958, to December 31, 2015, were collected. Data were analyzed from October 1, 2017, to March 31, 2019. <h3>Exposures</h3> Family history of breast cancer in FDRs and second-degree relatives (SDRs). <h3>Main Outcomes and Measures</h3> Primary invasive breast cancer diagnosis and the age at which women with different constellations of family history attained the risk level at which breast screening is usually recommended. <h3>Results</h3> Of the 5 099 172 women included in the study, 118 953 (2.3%) received a diagnosis of primary invasive breast cancer. A total of 102 751 women (86.4%; mean [SD] age at diagnosis, 55.9 [11.1] years) did not have family history of breast cancer in FDRs and SDRs at the time of their diagnosis. Risk-adapted starting age of breast cancer screening varied by number of FDRs and SDRs with breast cancer diagnosis and the age at diagnosis of the FDRs. For example, for screening recommendation at age 50 years for the general population (2.2% 10-year cumulative risk), women with multiple affected FDRs, with the youngest affected relative receiving a diagnosis before age 50 years, reached the benchmark risk level at age 27 years. When the youngest relative received a diagnosis after age 50 years, however, this risk level was attained at age 36 years. <h3>Conclusions and Relevance</h3> This study identifies possible risk-based starting ages for breast cancer screening based on population-based registers. These results may serve as high-quality evidence to supplement current screening guidelines for relatives of patients with breast cancer.
Real-World Outcomes of Ixazomib in the Treatment of Multiple Myeloma from a Single Center in China
Authors: Weiwei Sui, Gang An, Shuhui Deng, Yan Xu, Mu Hao, Fu Mingwei, Tingyu Wang, Shuhua Yi, Yaozhong Zhao, Dehui Zou, Zengjun Li, Lugui Qiu
Journal: Blood (2019)
Low-Dose Tamoxifen (LDTam) As a Breast Cancer (BC) Risk-Reduction Strategy in Lymphoma Survivors Exposed to Chest Radiation Therapy (RT) during Adolescence/Young Adulthood - a Randomized, Placebo-Controlled Double Blinded Phase IIb Trial
Authors: Smita Bhatia, Melanie Palomares, Lindsey Hageman, Yanjun Chen, Wendy Landier, Kandice Smith, Heidi Umphrey, Caroline A. Reich, Kathryn W. Zamora, Saro H. Armenian, Therese Bartholomew Bevers, Anne Blaes, Tara O. Henderson, David C. Hodgson, Melissa M. Hudson, Larissa Korde, Susan A. Melin, Sofia Merajver, Linda Overholser, Sandhya Pruthi, Lennie Wong, Judy Garber
Journal: Blood (2019)
EXTH-43. DYNAMIC MULTI-OMICS ANALYSIS OF MLN4924-TREATED GLIOBLASTOMA CELLS REVEALS ABSENCE OF PTEN AS A CANDIDATE DRIVER OF NEDDYLATION INHIBITION RESISTANCE
Authors: Brett Taylor, Shayesteh Ferdosi, Rita Bybee, Nanyun Tang, Sen Peng, Krystine Garcia-Mansfield, Victoria David-Dirgo, Ritin Sharma, Patrick Pirrotte, Michael Berens, Harshil Dhruv
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma multiforme (GBM) is the most lethal primary brain tumor and calls for novel therapeutic development. The neddylation pathway may be a therapeutic target, as global over activation of neddylation has been found in GBM patients and has correlated with shorter patient survival. Analogous to ubiquitination in reaction scheme and enzyme classes used, neddylation is a post-translational modification that is essential to many protein regulation and biological processes. Although non-cullin NEDD8 substrates have been investigated in recent years, the most well-characterized substrates of neddylation are the cullin subunits of Cullin-RING ligases (CRLs), which act as a scaffold for substrates to be ubiquitinated and degraded. The neddylation inhibitor MLN4924 targets NEDD8 Activating Enzyme (NAE), an upstream activator of neddylation, and induces cell cycle arrest, apoptosis and senescence in cancer cells. In this work, we investigated the context of vulnerability to Pevonedistat (MLN4924) in GBM. Efficacy of MLN4924 in glioma cell models was evaluated by measuring cell viability (CellTiterGlo®), colony formation efficiency, and cell cycle progression (flow cytometry with propidium iodide staining). GB1 (IC50= 0.28 μM), LN18 (IC50 = 0.19 μM), and GBM43 (IC50= 0.45 μM) were established as sensitive and M059K (IC50 = 5.5 μM), SNU1105 (IC50 = 20.9 μM), and GBM39 (IC50= 10.3 μM) as non-sensitive cell lines based on IC50 values. To discover genomic and/or proteomic markers of differential response, we collected RNA and protein from sensitive and non-sensitive cell lines after 0, 2, 8 and 24 hour treatment with MLN4924 for RNA sequencing and mass spectroscopy analyses. Multi-OMICS data point towards the absence of functional PTEN as a driver of MLN4924 resistance. Uncovering the mechanism underlying GBM’s vulnerability to MLN4924 will expand the knowledge of neddylation’s role in cancer and may arm physicians with an understanding of whether a GBM patient would respond to MLN4924 treatment or not.
Irradiation of Gastric Cancer
Authors: G. C. Fairchild, A. Shorter
Journal: BMJ (1947)

Effect on the Contraction of the Clot In the first experiment, with impure penicillin, it was noticed that in the tube containing 6,250 units per ml., in which clotting was much delayed, the clot did not contract.In the observation with pure penicillin the whole of the serum was drawn off after 24 hours and its volume measured.The amount of serum obtained from the con- trol was considerably greater than that from any of the tubes containing penicillin, indicating that even so little as 340 units per ml.had some retarding effect on the contrac- tion of the clot.Conclusions These results have no bearing on the systemic application of penicillin, as the concentration of the drug in the blood is then in the region of only 1 unit per ml.or less.However, it is quite easy to introduce locally sufficient to interfere seriously with coagulation and contraction of the clot.It would appear, therefore, that the local use of penicillin in an operation where the formation of a firm blood clot is of importance should be limited to washing out the cavity with a solution of the drug not exceeding 100 units per ml.This could, of course, be combined with intramuscular injections if there is any reason to fear wound infection by penicillin-sensitive organisms.
The Treatment of Hairy Cell Leukemia with a Focus on Long Lasting Responders to Cladribine: A Thirty-Year Experience from the Institute of Hematology of Bologna
Authors: Alessandro Broccoli, Carolina Terragna, Vittorio Stefoni, Cinzia Pellegrini, Beatrice Casadei, Miriam Marangon, Alice Morigi, Laura Nanni, Ginevra Lolli, Matteo Carella, Lisa Argnani, Michele Cavo, Pier Luigi Zinzani
Journal: Blood (2019)
Oral Contraceptives and Breast Cancer
Authors: M. J. Brennan
Journal: BMJ (1965)

latrogenic Ulcers of the Small Intestine SIR,--We should like to report another possible case of ileal ulceration and perforation in a patient receiving enteric-coated potassium-chloride tablets but not chlorothiazide.In June, 1964, a woman aged 58 was diagnosed as having pemphigus vulgaris.
RARE-07. HOW TO TREAT THE INCIDENTAL THALAMIC PRESUMED LOW-GRADE GLIOMAS
Authors: Toshihiro Kumabe, Ichiyo Shibahara, Masayuki Kanamori, Ryuta Saito, Takuichiro Hide, Sumito Sato, Yukihiko Sonoda, Teiji Tominaga
Journal: Neuro-Oncology (2019)

Abstract Medical intervention for patients with incidentally found presumed low grade gliomas (iLGGs) is controversial. We experienced 5 consecutive thalamic iLGGs, and discuss the follow-up methods and the timing of the intervention. Age at the initial MRI was 19, 57, 58, 70, 70, respectively. Only the bilateral thalamic iLGG of 19-year-old male was radically resected soon after the initial MRI, because of the large tumor size. The histological diagnosis was a diffuse astrocytoma, IDH-wildtype, without H3K27M mutation. This patient was treated by chemoradiation, still alive for 24 months with KPS of 90%. The other four cases were strictly followed by MRI. One case of 70-year-old female is followed for 38 months without increasing the tumor volume. The other 3 cases had been followed by MRI for 15, 91, 154 months, respectively. Stereotactic biopsy or ventriculo-peritoneal shunting (VPS) was performed after that because of the tumor progression. The histological diagnosis of 57-year-old male followed for 15 months was a diffuse astrocytoma, IDH-wildtype. This patient selected further follow-up, although volume of the tumor increased exponentially. Radical resection was performed 11 months after the stereotactic biopsy, disclosed malignant transformation. This patient was treated by chemoradiation, finally died of tumor dissemination 15 months after the radical resection. Long-term followed patients, such as 91 and 154 months, showed slow linear tumor volume increasing. The latter patient with bilateral iLGG was treated by VPS followed by radiation therapy. This patient could keep KPS of 100% for 13 years after the initial MRI and live for 20 years. Our case series suggests that conservative management and close follow-up of thalamic iLGGs is a safe and effective strategy. However, volumetric analysis must be performed for every follow-up MRI. Once the steep volume increasing is detected, surgical intervention and/or chemoradiation should be considered without delay.