tbuckley/cabot-search huggingface dataset:
ACTR-41. AN ARGUMENT THAT MORE ADJUVANT TEMOZOLOMIDE THERAPY IS BETTER FOR GLIOMA PATIENTS
Authors: Victor Levin, Alyssa Patel, Amy Le, Piia Thomas, Peak Scott
Journal: Neuro-Oncology (2019)

Abstract Current guidelines for adjuvant temozolomide (TMZ) treatment of glioma patients advocates 6 to 12 monthly cycles. Is that best? Will patients who receive &gt; 12 cycles live longer? To find out, we conducted a 10-year (2006–2016) chart review of 1300 glioma patients treated at NorCal Kaiser Permanente facilities to determine the impact of dose-week (AUC) quartiles and duration of TMZ therapy quartiles on median overall survival (mOS) in new low- and mid-grade gliomas (Group A) and glioblastoma (Group B) patients. Group A had 357 patients with WHO grade II and III astrocytic and oligodendroglial tumors; Group B had 943 patients with glioblastoma. The median AUC in Group A was 337 mg/m2 (IQR 129, 1095) and the median weeks of TMZ 15 (IQR 1, 42). In Group B, median AUC was 210 mg/m2 (IQR 79,581) and median weeks of TMZ 24 (IQR 9. 45). Based on quartile ranking of AUC, a higher AUC was found to be associated with longer mOS in Group A and B. In Group A, for increasing AUC quartiles, mOS was 134, 146, 369, and 397 weeks (p=0.0014); for Group B, mOs were 30, 48, 74, and 117 weeks (p&lt; 0.0001). Based on increasing quartiles for TMZ treatment duration for quartiles 2–4, Group A patient mOS increased from 122 weeks to 431 weeks (p = ns) and Group B patients, increased mOS from 51 to 143 weeks (p&lt; 0.0001). This retrospective analysis of 10-years of neuro-oncology practice brings into question limiting TMZ dose in WHO grade 2–3 glioma and WHO grade 4 glioblastoma patients as higher dose toleration and longer duration of treatment appears to be associated with longer mOS in both groups. Or does it show that patients who do well elect to take TMZ longer and maybe these findings reflect reverse causality?
Isolated Nasal Metastasis From Renal Cell Carcinoma 9 Years After Nephrectomy Seen on FDG PET
Authors: Yutang Yao, Zhuo Zuo, Zhuzhong Cheng
Journal: Clinical Nuclear Medicine (2019)

Abstract A 56-year-old man presented with intermittent epistaxis. Nasopharyngoscope revealed a hemorrhagic mass occupying the left nasal cavity. The patient had a history of renal clear cell carcinoma. 18 F-FDG PET/CT was performed to evaluate the potential lesions systematically. PET/CT images showed low to moderate activity in the region of nasal cavity and paranasal sinuses. No abnormal uptake of 18 F-FDG was observed in the rest of the body. Eventually, the mass was pathologically proved to be metastatic renal clear cell carcinoma.
Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Aggressive Natural Killer Cell Leukemia: An Advantage of Cord Blood Transplantation
Authors: Ayumi Fujimoto, Fumihiro Ishida, Koji Izutsu, Satoshi Yamasaki, Dai Chihara, Junji Suzumiya, Tetsuo Mitsui, Kazuteru Ohashi, Hideyuki Nakazawa, Hikaru Kobayashi, Junya Kanda, Takahiro Fukuda, Yoshiko Atsuta, Ritsuro Suzuki
Journal: Blood (2019)
Recurrent Chromosomal Abnormalities in Tumoral Lesions of Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia: A Large-Scale Fluorescent in-Situ Hybridization Study on Tissue Biopsy Sections
Authors: Pedro Horna, Kathryn E. Pearce, Rhett P. Ketterling, Jess Peterson
Journal: Blood (2019)
Hypoxia in patients with acute hemiplegia.
Authors: M J Walshaw, M G Pearson
Journal: BMJ (1984)

Sixteen patients with an early dense hemiplegia due to cerebrovascular accidents were shown to have a greater degree of hypoxia than 16 matched control patients. The patients with hemiplegia had a reflex compensatory fall in arterial carbon dioxide tensions (PaCO2) with possible reduction in cerebral blood flow. Oxygen treatment led to an increase in PaCO2 in the patients with hemiplegia, but the increase in oxygen tensions in these patients was significantly less than that in the control group, suggesting increased pulmonary shunting as the cause for the hypoxia. Oxygen treatment may improve cerebral blood flow and oxygenation and have a useful role in the early management of patients with a dense hemiplegia.
The Revised Myeloma Comorbidity Index (R-MCI) As a Promising Approach for Predicting Overall (OS)- and Progression-Free (PFS) Survival and Optimizing Therapy Strategies in Multiple Myeloma (MM) Patients (pts) - Comparative Analysis of 5 Comorbidity Indices (CI), Including Retro- and Prospective Applicability
Authors: Katja Schoeller, Gabriele Ihorst, Sophia Scheubeck, Max Holler, Sandra M. Woerner, Heike Reinhardt, Stefan P. Müller, Justus Duyster, Ralph Wäsch, Monika Engelhardt
Journal: Blood (2019)
Efficacy and Safety of BAY 94-9027 (Damoctocog Alfa Pegol) Prophylaxis in Patients with Severe Hemophilia a and Comorbidities: A Post Hoc Analysis of PROTECT VIII Data
Authors: Wolfgang A. Miesbach, Giovanni Di Minno, Elena Santagostino, Dr. Klamroth, Inga Bayh, Amaryllis Soto, Cedric Hermans
Journal: Blood (2019)
Can circular RNAs be used as prenatal biomarkers for congenital diaphragmatic hernia?
Authors: Richard Wagner, Aruni Jha, Lojine Ayoub, Shana Kahnamoui, Daywin Patel, Thomas H. Mahood, Andrew J. Halayko, Martin Lacher, Christopher D. Pascoe, Richard Keijzer
Journal: European Respiratory Journal (2019)

<b>Circular RNAs are dysregulated in lungs of congenital diaphragmatic hernia patients, a malformation of the lung and diaphragm. These results suggest that they can serve as prenatal biomarkers to improve prognostication and diagnostic accuracy.</b>http://bit.ly/2Cz7Bzm
Challenges in Colorectal Cancer
Authors: M ALLEN
Journal: Gut (2001)

Challenges in Colorectal Cancer . Edited by J H Scholefield (Pp230; illustrated; £69.50). Oxford, UK: Blackwell Science, 2000. ISBN 0 63205 116 7.

If asked to supply a subtitle for this excellent eminently readable book, I would suggest “All you ever wanted to know about the basics of colorectal cancer but were afraid to ask because you assumed that people would expect you to know already”. The chapters are written by experts renowned in their field and each topic is dealt with comprehensively and clearly with the reader being led from one line of argument to the next in a satisfyingly logical way. Although aimed at the clinician rather than the scientist, where necessary the scientific evidence is given in sufficient detail without …
Relationship between the single nucleotide polymorphism rs4704963 (T&gt; C) of the Early B-Cell Factor 1 gene and smoking in a population with risk factors for coronary heart disease with and without acu
Authors: Carbajales J Carbajales J
Journal: Clinical Cardiology and Cardiovascular Interventions (2019)

Introduction:Early B-cell factor 1 (EBF1) gene participates in the development of the central nervous system and is expressed in adipocytes and olfactory neuroepithelium, which is intimately linked with the emotion and reward system in adults.For this reason, it could be linked to tobacco addiction Objective: The aim of this study was to determine probable association between the EBF1 gene rs4704963 SNP (T>C) with smoking habits in a population of patients with multiple coronary risk factors (CRF) with and without acute coronary syndromes (ACS).Materials and methods: Between December 2015 and March 2017, 104 consecutive patients with two or more risk factors, with or without ACS were included.A 10-mL blood sample was collected from all the patients for SNP determination.DNA genotyping was carried out using the nested PCR technique and subsequent sequencing.Results: Mean age was 59.1 ± 9.17 years and 59.6% were men.The most common CRF were smoking habits (60.6%) hypertension (56.7%) and diabetes (48.1%).None of the patients had the homozygous T / T haplotype while 17 patients (16.3%) presented the T / C haplotype for heterozygous SNP.Among the 17 patients with the SNP detected, 16 (94.1%)were smokers compared to 54% of smokers in those patients without the SNP detected (p = 0.002).In those patients with ACS and smoking habits, the SNP was detected in 21.3% versus 0% in those with ACS and no history of smoking habits (p= 0.029) Conclusion: A significant association was observed between the EBF1 gene rs4704963 SNP (T> C) with smoking habits in patients with ACS and in those with CRF without ACS.Further research including more patients is necessary to confirm these findings in order to customize decision-making to prevent this addiction and indicate the appropriate treatment when smoking is present.
Downregulation of MDM2 Leads to Anti-Proliferative Effects through Activation of p53-Associated Pathway Mediated By Both Dual Inhibitor MX69 and Mir-548c-3p in Multiple Myeloma
Authors: Faruq Faruq, Davidson Zhao, Jian Wu, Jonahunnatha Nesson George William, Min Zhang, Hong Chang
Journal: Blood (2019)
Prognostic Significance of FOXO3 in Pediatric Acute Myeloid Leukemia (AML) Patients Treated with Bortezomib Addition to Standard Therapy: Results from a Children's Oncology Group Phase 3 Clinical Trial
Authors: Anneke D. van Dijk, Peter P. Ruvolo, Fieke W Hoff, Yihua Qiu, Alan S Gamis, Richard Aplenc, Anders E. Kolb, Todd A. Alonzo, Robert B. Gerbing, Eveline S. de Bont, Sophia W.M. Bruggeman, Terzah M Horton, Steven M. Kornblau
Journal: Blood (2019)
Crohn's disease.
Authors: G. Slaney
Journal: BMJ (1968)

Though this relatively uncommon but serious and perplexing disease was first described as a clinical entity by Crohn and his associates in 1932, sporadic cases had been previously recorded, probably the first by Morgagni in 1769.Originally designated terminal ileitis, then regional ileitis, and subsequently amended to "regional enteritis," it is now known that the disease can also affect the colon or jejunum, and rarely the stomach or duodenum may be involved.Most British gastro- enterologists, therefore, prefer to use the eponymous term Crohn's disease qualified by its site, since this avoids the use of such confusing terms as ileocolitis, granulomatous enteritis, enterocolitis, regional or segmental colitis, and so on to describe the same condition. AetiologyThe cause of the disease remains unknown.It is not related to sarcoidosis, and there is no convincing evidence that bac- terial or viral infections play any part in its aetiology.There is now conclusive evidence that Crohn's disease is not tuber- culous in nature, but it must be remembered that ileocaecal tuberculosis still occurs, particularly among the immigrant population, and this possibility must always be considered in the differential diagnosis.The disease has a definite familial incidence, and a sufficient number of sporadic reports have now appeared in the literature describing its development following severe nonpenetrating abdominal trauma to indicate that this may occasionally be an aetiological factor.The cellular infiltration in the bowel wall in Crohn's disease is a striking feature, consisting predominantly of plasma cells and lymphocytes associated with giant cell systems and sometimes tissue eosinophilia.These are charac- teristic features of an immune-hypersensitivity reaction, and indeed similar but not identical lesions can be produced experi- mentally in the alimentary tract of appropriately sensitized animals.However, detailed immunological studies have failed to substantiate the suggestion that Crohn's disease is an auto- immune or hypersensitivity disorder, though the features of the disease and its response to various forms of therapy lead many clinicians to continue to suspect that it probably is.The con- dition may present clinically as an acute or chronic problem- the latter being much more common. Acute Regional IleitisThe patient, usually a child, an adolescent, or a young adult, presents with signs and symptoms resembling those of acute appendicitis-colicky abdominal pain, tenderness in the right iliac fossa, and a fever of 100 to 1010 F. (37.8 to 38.40 C.).The terminal ileum is commonly involved, being reddened or purple in colour, swollen, and oedematous, with a marked
Targeting Extracellular Vesicle Secretion As a Strategy to Overcome Microenvironment Mediated Drug Resistance in Acute Myeloid Leukemia
Authors: Palani Kumar Kumar, Saravanan Ganesan, Nithya Balasundaram, Sachin David, Arvind Venkatraman, Uday Prakash Kulkarni, Anu Korula, Biju George, Poonkuzhali Balasubramanian, Vikram Mathews
Journal: Blood (2019)
Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical, Clinical, and Correlative Studies
Authors: Jacqueline S Garcia, Helen I. Gandler, Geoffrey Fell, Ashlee J. Fiore, Donna S Neuberg, Adrienne Anderson, Kelsey O'Day, Marlise Luskin, Martha Wadleigh, Eric S. Winer, Ilene Galinsky, Daniel J. DeAngelo, David A. Frank, Richard M. Stone
Journal: Blood (2019)
IMMU-48. RATIONAL DEVELOPMENT AND CHARACTERIZATION OF MULTIVALENT TARGETING TANDEM AND PARALLEL CAR T CELLS FOR GLIOMA
Authors: Yibo Yin, Radhika Thokala, Logan Zhang, Devneet Kainth, Leila Haddad, Zev Binder, Zhiguo Lin, Donald O’Rourke
Journal: Neuro-Oncology (2019)

Abstract High grade glioma is the most common malignant primary brain tumor. Despite the best available therapy, the median survival is limited. Chimeric antigen receptor (CAR)-T cells effectively attack target positive tumor cells, demonstrating a promising possible treatment. Based on our previous clinical and pre-clinical studies, we utilized epidermal growth factor receptor variant III (EGFRvIII) and interleukin 13 receptor subunit alpha 2 (IL13Rα2) targeting single-chain variable fragments (scFvs) to generate bi-specific tandem CAR T cells and bi-specific parallel CAR T cells to decrease the potential of antigen escape and tumor recurrence. 5, 10, 15 or 20 flexible amino acids were utilized to link scFvs in tandem CARs. Ribosomal “skipping” 2A peptides were utilized to generate parallel CAR T cells. Flow-based IL13Rα2 staining on glioma stem cells (GSCs) showed 7 out 11 cases positive (64%) heterogeneous intratumoral expression. Tandem CAR T cells and parallel CAR T cells upregulated CD69 expression (P&lt; 0.0001), generated IFNγ, interleukin 2 and TNFα (P&lt; 0.0001), as well as exhibiting cytotoxic activity (P&lt; 0.0001) when compared against un-transduced T cells, in co-culture with either single- or double-target positive GSCs. There was no significant difference between different lengths of linker in tandem CAR T cells. Parallel CAR T cells generated a larger cytokine response (P&lt; 0.0001) and more effectively killed target positive cells (P&lt; 0.05) than tandem CAR T cells. In summary, glioma associated target expression is heterogeneous in GSCs. Multivalent tandem CAR T cells and parallel CAR T cells effectively respond to target expressing tumor cells. The function of tandem CAR T cells is not relative with the length of linker. Parallel CAR T cells are a more promising strategy in generating gene modified multivalent targeting T cells.
Oral Contraceptives and Breast Cancer
Authors: G. Lloyd
Journal: BMJ (1964)

We believe' that some if not most cases of this condition belong to the group of collagen disorders, many probably being connected in some way with rheumatoid disease.We are unconvinced by the arguments advanced that an alteration of nomenclature at this juncture for a condition whose aetiology remains obscure is likely to be of any advantaged-We are, etc.,
Protocol for an International, Multi-Centre, Retrospective Study to Describe Treatment Pathways, Outcomes and Resource Use in Patients with Multiple Myeloma (INTEGRATE)
Authors: Su-Peng Yeh, Fahad Alsharif, Meral Beksac, Wenming Chen, Dorotea Fantl, Tatiana Mitina, Estelle Verburgh, Wee Joo Chng, Kwang-Wei Wu, Zijing Zhang, Hui Wan, Kihyun Kim
Journal: Blood (2019)
Characterization of organic anion transporting polypeptide 1b2 knockout rats generated by CRISPR/Cas9: a novel model for drug transport and hyperbilirubinemia disease
Authors: Xinrun Ma, Xuyang Shang, Xuan Qin, Jian Lu, Mingyao Liu, Xin Wang
Journal: Acta Pharmaceutica Sinica B (2019)

Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1/3) as important uptake transporters play a fundamental role in the transportation of exogenous drugs and endogenous substances into cells. Rat OATP1B2, encoded by the Slco1b2 gene, is homologous to human OATP1B1/3. Although OATP1B1/3 is very important, few animal models can be used to study its properties. In this report, we successfully constructed the Slco1b2 knockout (KO) rat model via using the CRISPR/Cas9 technology for the first time. The novel rat model showed the absence of OATP1B2 protein expression, with no off-target effects as well as compensatory regulation of other transporters. Further pharmacokinetic study of pitavastatin, a typical substrate of OATP1B2, confirmed the OATP1B2 function was absent. Since bilirubin and bile acids are the substrates of OATP1B2, the contents of total bilirubin, direct bilirubin, indirect bilirubin, and total bile acids in serum are significantly higher in Slco1b2 KO rats than the data of wild-type rats. These results are consistent with the symptoms caused by the absence of OATP1B1/3 in Rotor syndrome. Therefore, this rat model is not only a powerful tool for the study of OATP1B2-mediated drug transportation, but also a good disease model to study hyperbilirubinemia-related diseases.
TMIC-11. ENHANCED B7-H4 EXPRESSION IN GLIOMAS WITH LOW PD-L1 EXPRESSION IDENTIFIES COLD TUMORS
Authors: Di Chen, Gaopeng Li, Chunxia Ji, Qiqi Lu, Ying Qi, Chao Tang, Ji Xiong, Jian Hu, Dave S B Hoon, Yan Zhang, Yu Yao, Liangfu Zhou
Journal: Neuro-Oncology (2019)

Abstract The expression profiles of different immune checkpoint molecules are promising for triaging personalized targeted immunotherapy. Gliomas have been shown as potential targets for immune checkpoint inhibitors. Our study was performed to determine co-expression levels of two major B7 immune molecules PD-L1 and B7-H4 in gliomas in which both have demonstrated to inhibit anti-tumor host immunity. We assessed tumor issues from primary gliomas stage II–IV(n=505) by immunohistochemistry (IHC) for protein levels of both PD-L1 and B7-H4. Gene co-expression analysis assessing clusters based on extent of PD-L1/B7-H4 classifier genes expression were investigated in two transcriptome datasets (TCGA and CGGA) to validate IHC expression profiles. Here, we found that 61% and 54% of patient samples were positive for PD-L1 and B7-H4 respectively, whereby high-expression of either protein was limited to 23% and 20% respectively. Co-expression of PD-L1 and B7-H4 in high levels was limited to 2%. Comparable results were seen in RNA-seq datasets when PD-L1 mRNA expression level corelated negatively with B7-H4. Gene co-expression modules clustered in each grade gliomas without Double-High modules (glioma cluster with high mRNA expression of both PD-L1 and B7-H4 classifier genes) also verified restricted co-expression pattern. B7-H4 mRNA expression level had negative correlation with extent of immune cell infiltration, including tumor-infiltrating lymphocytes (TILs), and High-B7-H4 module gliomas (high B7-H4 but low PD-L1 classifier genes expression) were related to a cold tumor with less TILs. The majority of gliomas express PD-L1 or B7-H4, however, co-expression of both at high levels is minimal. The High-B7-H4 module was significantly lacking in TILs, suggesting that B7-H4 might inhibit T cell trafficking into the central nervous system (CNS). This study demonstrates that PD-L1 expression alone is not fully informative in gliomas for immune targeted or active-specific immunotherapy, and PD-L1 and B7-H4 probably inhibit different aspects of the T cell functions.
Characterization of 5B9, a Chimeric Monoclonal Anti-PF4/H Antibody with a Human Fc Fragment and Which Mimics the Effects of HIT Human Antibodies
Authors: Jérome Rollin, Claire Kizlik-Masson, Steven McKenzie, Anne Poupon, Yuhang Zhou, Caroline Vayne, Gaël Champier, Claire Pouplard, Yves Gruel
Journal: Blood (2016)
Pulmonary Alveolar Proteinosis
Authors: Samuel H. Rosen, Benjamin Castleman, Averill A. Liebow, Frank M. Enzinger, Richard T. N. Hunt
Journal: New England Journal of Medicine (1958)

WITHIN the past five years, and at an increasing rate within recent months, we have encountered 27 cases of a remarkable disease of the lung that consists of the filling of the alveoli by a PAS-positive proteinaceous material, rich in lipid. This material appears to be produced by the lining cells, which slough into the lumen, ultimately becoming necrotic and yielding granules and variable laminated bodies to the alveolar content. The condition bears certain resemblances to pneumocystis infection of the lung,1 2 3 4 5 6 7 8 9 and, indeed, the possibility was considered that it represented a "burnt-out" phase of this disease. Several cases that we . . .
Outcome and molecular features of head and neck squamous cell carcinomas (HNSCC) bearing a p16 high phenotype
Authors: D. Psyrri, E. Pectasides, P. Weinberger, C. Sasaki, B. Burtness, G. Fountzilas
Journal: Journal of Clinical Oncology (2009)

6031 Background: We have previously demonstrated that p16 expression defines a biologically distinct subgroup of oropharyngeal squamous cell cancers (OSCC). Thus, OSCC can be Class I: human papillomavirus (HPV)-, Class II: HPV16+/p16-, or Class III: HPV16+/p16+. Tumors bearing a high p16 phenotype were associated with superior outcome. Using in situ automated quantitative protein expression analysis (AQUA) to explore the biomarker signatures of these 3 classes we found that beta-catenin, epidermal growth factor receptor (EGFR) and Met were upregulated in class III tumors. Our aim was to validate these findings using an independent cohort. Methods: A tissue microarray composed of 122 specimens from primary HNSCC cases treated with either external beam radiotherapy (EBRT) or gross total surgical resection and EBRT was constructed. Protein expression levels for a panel of 13 markers (EGFR, MET, STAT 3, ERK 1/2, pAkt, PI3Kp85, PI3Kp110, PTEN, p53, Bcl-2, E-cadherin, β-catenin, NFκB) were analyzed using AQUA. P16 protein levels were correlated with progression-free (PFS) and overall survival (OS). Survival analysis was performed by Kaplan-Meier method with log-rank test for assessing statistical significance.Comparison of expression between the p16 positive and p16 negative groups was done using unpaired t-tests. Results: Mean follow-up time for the cohort was 40 months. AQUA scores were divided into quartiles. Survival analysis showed that patients in the top quartile had a significantly better DFS (p = 0.01) and OS (p = 0.002). In multivariable analysis, adjusting for well-characterized prognostic variables, p16 expression retained its prognostic significance. Expression of E-cadherin and β-catenin was significantly higher in the p16 positive versus the p16 negative group (p = 0.014 and p = 0.006, respectively). p16 positive tumors also expressed higher levels of PTEN (p = 0.0009), PI3Kp110 (p = 0.03), NFκB (p = 0.007), and Bcl-2 (p = 0.005). Conclusions: These results validate p16 as a favorable prognostic marker in HNSCC. They also validate beta-catenin as a distinct biomarker in HNSCC bearing high p16 phenotype. Given that HPV+ tumors are p16+, beta-catenin is a candidate biomarker that distinguishes HPV + versus HPV - HNSCC. No significant financial relationships to disclose.
Phospho-Proteomic Profiling of T-Cell Acute Lymphoblastic Leukemia Identifies Specific Kinase Activation Signatures That Can Predict Response to Targeted Therapy
Authors: Valentina Cordo', Rico Hagelaar, Sander Piersma, Thang V Pham, Connie Jimenez, Jules P.P. Meijerink
Journal: Blood (2019)