tbuckley/cabot-search huggingface dataset:
Alloreactivity: the Janus-face of hematopoietic stem cell transplantation
Authors: A Gratwohl, A Sureda, J Cornelissen, J Apperley, P Dreger, R Duarte, H T Greinix, E Mc Grath, N Kroeger, F Lanza, A Nagler, J A Snowden, D Niederwieser, R Brand
Journal: Leukemia (2017)

Differences in major and minor histocompatibility antigens between donor and recipient trigger powerful graft-versus-host reactions after allogeneic hematopoietic stem cell transplantation (HSCT). The clinical effects of alloreactivity present a Janus-face: detrimental graft-versus-host disease increases non-relapse mortality, beneficial graft-versus-malignancy may cure the recipient. The ultimate consequences on long-term outcome remain a matter of debate. We hypothesized that increasing donor-recipient antigen matching would decrease the negative effects, while preserving antitumor alloreactivity. We analyzed retrospectively a predefined cohort of 32 838 such patients and compared it to 59 692 patients with autologous HSCT as reference group. We found a significant and systematic decrease in non-relapse mortality with decreasing phenotypic and genotypic antigen disparity, paralleled by a stepwise increase in overall and relapse-free survival (Spearman correlation coefficients of cumulative excess event rates at 5 years 0.964; P<0.00; respectively 0.976; P<0.00). We observed this systematic stepwise effect in all main disease and disease-stage categories. The results suggest that detrimental effects of alloreactivity are additive with each step of mismatching; the beneficial effects remain preserved. Hence, if there is a choice, the best match should be donor of choice. The data support an intensified search for predictive genomic and environmental factors of 'no-graft-versus-host disease'.
Immunotherapy biomarkers 2016: overcoming the barriers
Authors: James L. Gulley, Jay A. Berzofsky, Marcus O. Butler, Alessandra Cesano, Bernard A. Fox, Sacha Gnjatic, Sylvia Janetzki, Shyam Kalavar, Vaios Karanikas, Samir N. Khleif, Ilan Kirsch, Peter P. Lee, Cristina Maccalli, Holden Maecker, Jeffrey Schlom, Barbara Seliger, Janet Siebert, David F. Stroncek, Magdalena Thurin, Jianda Yuan, Lisa H. Butterfield
Journal: Journal for ImmunoTherapy of Cancer (2017)

This report summarizes the symposium, 'Immunotherapy Biomarkers 2016: Overcoming the Barriers', which was held on April 1, 2016 at the National Institutes of Health in Bethesda, Maryland. The symposium, cosponsored by the Society for Immunotherapy of Cancer (SITC) and the National Cancer Institute (NCI), focused on emerging immunotherapy biomarkers, new technologies, current hurdles to further progress, and recommendations for advancing the field of biomarker development.
PP53. PROMS IN NEUROSURGERY: WHERE ARE WE NOW?
Authors: Dr Prajwal Ghimire, Ms Victoria Hurwitz, Prof Keyoumars Ashkan
Journal: Neuro-Oncology (2017)

INTRODUCTION: Patient reported outcome measures (PROMs) play important role in addressing health related quality of life of patients and their outcome satisfaction. Neurosurgery is lagging behind in disease specific PROMs and there is an urgent and emerging need for disease specific PROMs for neurosurgery especially neuro-oncology to address specific quality of life issues, outcome satisfaction and patient safety. METHODS: A search in MEDLINE, PUBMED, EMBASE and WEB of Science databases was done for articles related to neurosurgery PROMs and 72 relevant articles were identified among 4473 articles. Twenty nine different PROMs were analysed from the relevant articles in terms of factions tested, advantages, disadvantages, limitations and scope in neurosurgery. RESULTS: The extensive search resulted in the data suggesting that generic PROMs are still in use in neurosurgery and multiple disadvantages has been identified giving rise to a strong scope and need of disease specific neurosurgical PROMs. CONCLUSION: Currents generic PROMs do not address the disease specific outcome issues of neurosurgery and thus there is a definite need of disease specific PROMs especially neuro-oncology so that the patient satisfaction and safety as well as quality of life issues can be addressed systematically. KEYWORDS: PROMs, Neurosurgery, brain tumours
miR-19a promotes colorectal cancer proliferation and migration by targeting TIA1
Authors: Yanqing Liu, Rui Liu, Fei Yang, Rongjie Cheng, Xiaorui Chen, Shufang Cui, Yuanyuan Gu, Wu Sun, Chaoying You, Zhijian Liu, Feng Sun, Yanbo Wang, Zheng Fu, Chao Ye, Chenyu Zhang, Jing Li, Xi Chen
Journal: Molecular Cancer (2017)

Colorectal cancer (CRC) is a major worldwide health problem due to its high prevalence and mortality rate. T-cell intracellular antigen 1 (TIA1) is an important tumor suppressor involved in many aspects of carcinogenesis and cancer development. How TIA1 expression is regulated during CRC development remains to be carefully elucidated.In CRC tissue sample pairs, TIA1 protein and mRNA levels were monitored by Western blot and qRT-PCR, respectively. Combining meta-analysis and miRNA target prediction software, we could predict microRNAs that targeted TIA1. Next, three CRC cell lines (SW480, Caco2 and HT29) were used to demonstrate the direct targeting of TIA1 by miR-19a. In addition, we investigated the biological effects of TIA1 inhibition by miR-19a both in vitro by CCK-8, EdU, Transwell, Ki67 immunofluorescence and Colony formation assays and in vivo by a xenograft mice model.In colorectal cancer (CRC), we found that TIA1 protein, but not its mRNA, was downregulated. We predicted that TIA1 was a target of miR-19a and validated that miR-19a binded directly to the 3'-UTR of TIA1 mRNA. miR-19a could promote cell proliferation and migration in CRC cells and accelerated tumor growth in xenograft mice by targeting TIA1.This study highlights an oncomiR role for miR-19a in regulating TIA1 in CRC and suggests that miR-19a may be a novel molecular therapeutic target for CRC.
Impact of Partial Response Versus Complete Response before RIC/RTC Allogeneic Stem Cell Transplantation on Survival in a Cohort of 115 Chemosensitive Advanced NHL
Authors: Sylvain Garciaz, Anne Wanquet, Luca Castagna, Roberto Crocchiolo, Sabine Fürst, Samia Harbi, Christian Chabannon, Florence Broussais, Diane Coso, Reda Bouabdallah, Didier Blaise
Journal: Blood (2014)
Pre-Emptive Rituximab for Epstein-Barr Virus Reactivation Post Stem Cell Transplant: High CRP and PTLD At Initiation of Treatment Confer Inferior Outcome
Authors: David Burns, Sandeep Nagra, Husam Osman, Ram Malladi, Manoj Raghavan, Fiona Clark, Mark Cook, Prem Mahendra, Charles Craddock, Sridhar Chaganti
Journal: Blood (2011)
Outcome of Patients with Myeloproliferative Disorders Treated with Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Michele L. Donato, Angela Prann, Anna Ullrich, Tatyana Feldman, Stuart L. Goldberg, Andre Goy, Aisha Masood, Andrew L. Pecora, David S. Siegel, Scott D. Rowley
Journal: Blood (2008)
Abstract P1-06-06: Evidence for tumor heterogeneity and clonal evolution during invasive progression of breast cancer
Authors: Y Ding, JR Marks, LM King, AH Hall, ER Mardis, AG Rodrigo, CC Maley, E-S Hwang
Journal: Cancer Research (2017)

Abstract Purpose: Intratumoral heterogeneity is well recognized to be an important driver of treatment resistance and metastasis. We undertook this N of one study to measure the degree of heterogeneity in a single large preinvasive lesion with an invasive component to determine the relationship between tumor heterogeneity, spatial distribution, clonal evolution, and invasive progression. Methods: We identified a patient with extensive DCIS measuring 7.5 cm, associated with 1.5 cm of an invasive component. We segregated the tumor sample into 32 unique blocks with precise geospatial localization; invasive cancer was identified in 3 of 32 blocks. NGS libraries were made from FFPE derived DNA (20-40ng) for full exome sequencing and hybridization to a 4.8 million element SNP array. All data were analyzed and a phylogentic tree was constructed. Results: The sequence data was analyzed with Platypus[1] and 3922 somatic mutation sites were found in total. These sites were concatenated into one sequence for each sample. Then a Neighbor-Joining tree was built with a Jukes-Cantor model and 1000 bootstrap replicates using FastME 2.0[2], to assess the reliability of the tree (Figure 1). Phylogenetic analysis revealed that invasive cancer evolved twice, independently. Dense sampling allowed reconstruction of the temporal order of mutations that accumulated in the cell lineage of the invasive cancers. Furthermore, the phylogeny revealed that distant regions may be closely genetically related, the oldest parts of the tumor were in the interior of the tumor, and that the invasive tumors evolved near the oldest parts of the tumor, rather than at the expanding front. Conclusions: Extensive sampling and sequencing of a single tumor yields important insights about tumor heterogeneity and tumor progression for DCIS to invasive cancer. Foci of invasion were geospatially associated with preinvasive regions of progressively higher mutational load. 1. Rimmer A, Phan H, Mathieson I, Iqbal Z, Twigg SR, Wilkie AO, McVean G, Lunter G, Consortium W: Integrating mapping-, assembly-and haplotype-based approaches for calling variants in clinical sequencing applications. Nature genetics 2014, 46(8):912-918. 2. Lefort V, Desper R, Gascuel O: FastME 2.0: a comprehensive, accurate, and fast distance-based phylogeny inference program. Molecular biology and evolution 2015:msv150. Citation Format: Ding Y, Marks JR, King LM, Hall AH, Mardis ER, Rodrigo AG, Maley CC, Hwang E-S. Evidence for tumor heterogeneity and clonal evolution during invasive progression of breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-06-06.
Computational Algorithm Based On Serum Immunoassays for the Identification of Haematological Disease May Identify Patients with Other Acute Disorders
Authors: David Sutton, Jeffrey Faint, Anandram Seetharam, Alan Macwhannell, Stephen Harding, Abe Jacob, Sunil Honda, Ladan Mirbahai, Supratik Basu
Journal: Blood (2012)
Vitamin K2 Modulates Differentiation and Apoptosis of Both Myeloid and Erythroid Lineages
Authors: Eriko Sada, Yasunobu Abe, Rie Ohba, Yoshimichi Tachikawa, Eriko Nagasawa, Shiratshuchi Motoaki, Ryoichi Takayanagi, Tsukuru Umemura
Journal: Blood (2010)
Targeting mTOR Signaling Can Prevent the Progression of FSGS
Authors: Stefan Zschiedrich, Tillmann Bork, Wei Liang, Nicola Wanner, Kristina Eulenbruch, Stefan Munder, Björn Hartleben, Oliver Kretz, Simon Gerber, Matias Simons, Amandine Viau, Martine Burtin, Changli Wei, Jochen Reiser, Nadja Herbach, Maria-Pia Rastaldi, Clemens D Cohen, Pierre-Louis Tharaux, Fabiola Terzi, Gerd Walz, Markus Gödel, Tobias B Huber
Journal: Journal of the American Society of Nephrology (2017)

Mammalian target of rapamycin (mTOR) signaling is involved in a variety of kidney diseases. Clinical trials administering mTOR inhibitors to patients with FSGS, a prototypic podocyte disease, led to conflicting results, ranging from remission to deterioration of kidney function. Here, we combined complex genetic titration of mTOR complex 1 (mTORC1) levels in murine glomerular disease models, pharmacologic studies, and human studies to precisely delineate the role of mTOR in FSGS. mTORC1 target genes were significantly induced in microdissected glomeruli from both patients with FSGS and a murine FSGS model. Furthermore, a mouse model with constitutive mTORC1 activation closely recapitulated human FSGS. Notably, the complete knockout of mTORC1 by induced deletion of both Raptor alleles accelerated the progression of murine FSGS models. However, lowering mTORC1 signaling by deleting just one Raptor allele ameliorated the progression of glomerulosclerosis. Similarly, low-dose treatment with the mTORC1 inhibitor rapamycin efficiently diminished disease progression. Mechanistically, complete pharmacologic inhibition of mTOR in immortalized podocytes shifted the cellular energy metabolism toward reduced rates of oxidative phosphorylation and anaerobic glycolysis, which correlated with increased production of reactive oxygen species. Together, these data suggest that podocyte injury and loss is commonly followed by adaptive mTOR activation. Prolonged mTOR activation, however, results in a metabolic podocyte reprogramming leading to increased cellular stress and dedifferentiation, thus offering a treatment rationale for incomplete mTOR inhibition.
Ferritin Heavy Chain, a Repressor of the Human β-Globin Gene That Binds a Conserved Cagtgc Motif, Is Bound to the Repressed β-Globin Promoter In Vivo in K562 Cells and Specifically Binds an Analogous Site in the Mouse βMajor-Globin Promoter.
Authors: Robert H. Broyles, Visar Belegu, Charles A. Stewart, Quentin N. Pye, Austin C. Roth, Katharine M. Harris, Robert A. Floyd, Klodianna Jani, Marie Trudel
Journal: Blood (2004)
ReGISTry Study of High Risk GIST Patients After Complete Resection:The adjuvant therapy and pathological diagnosis in Japan.
Authors: Toshirou Nishida, Yuko Kitagawa, Yukinori Kurokawa, Yoshito Komatsu, Chikashi Ishioka, Toshihiko Doi, Yasuhide Yamada, Masato Ozaka, Haruhiko Cho, Tetsuo Kanda, Toshiro Sugiyama, Akira Sawaki, Yoshihiro Kakeji, Toshihiro Hirai, Shinji Hato, Hideo Baba, Kuniaki Shirao, Seiichi Hirota, Tatsuo Kagimura
Journal: Journal of Clinical Oncology (2015)

10533 Background: Although three-year imatinib adjuvant therapy is recommended by GIST guidelines, there is a lack of clinical data regarding use of adjuvant therapy, adherence, and indications. A prospective registry study for high-risk GIST progressing in Japan examined reality of adjuvant in clinical practice. Methods: Between Dec. 2012 and Dec. 2014, 398 pts with histologically-confirmed high-risk GIST in local site were registered. There were 214 males and 184 females with median age of 64 yrs. In the central, H&E, immunohistochemistry, and genotyping were done. Results: Disease was located in the stomach (n = 238), small intestine (n = 122), large intestine (n = 26), or others (n = 12). Median tumor size was 8.0 cm and median mitosis (local pathology) was 10/50HPF. Tumor rupture was seen in 52 pts (13%) and 49 pts had received neoadjuvant therapy. After surgery, adjuvant therapy was administered for 304 pts (76%) and withheld for 82 pts (21%). PS of pts with adjuvant therapy was 0 (258 pts), 1 (37 pts) and > 2 (2 pts). Tumor cell type included spindle (n = 327), epithelioid (n = 14) and mixed (n = 33) histology by pathological test at each hospital. Central pathological review was done for 272 pts: KIT was positive in 263 pts (97%), DOG1 in 262 pts (96%), and CD34 in 228 pts (84%). Mutations were analyzed in 260 pts including 209 KIT exon 11 mutations, 15 KIT exon 9 mutations, 8 other KIT mutations, 10 PDGFRA exon18 mutations, 1 PDGFRA exon 12 mutations, and 6 wild type GISTs. Although KIT immunoreactivity was consistent between central and local (concordance = 92%), CD34 immunoreactivity showed lower concordance (76%) and 10 pts (3.7%) were diagnosed as non-GIST in the central review. There was significant correlation between local and central mitotic counts, but median mitotic count by central review (5/50 HPF) was significantly lower than local values, which resulted in 46 pts (18%) was not diagnosed as high-risk in central. Conclusions: Adjuvant imatinib was used for 76% of high risk GIST pts locally diagnosed. There are some disparities in the pathological review of high risk GIST between local and central pathologists, which may indicate requirement of improvement in pathological concordance of GIST. Clinical trial information: UMIN000009531.
In uncomplicated, left-sided acute diverticulitis, observation did not differ from antibiotics for recovery
Authors: Anna C. Juncadella, Joseph D. Feuerstein
Journal: Annals of Internal Medicine (2017)

Source Citation Daniels L, Unlu C, de Korte N, et al; Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017;104:52-61. 27686365
Pulmonary Oxygen Toxicity
Authors: W. Bruce Davis, Stephen I. Rennard, Peter B. Bitterman, Ronald G. Crystal
Journal: New England Journal of Medicine (1983)

To study the early changes in the lower respiratory tract in persons exposed to periods of hyperoxia usually considered safe, we evaluated 14 normal subjects by bronchoalveolar lavage before and immediately after 16.7±1.1 hours of breathing more than 95 per cent oxygen. Hyperoxia caused a significant alveolar-capillary "leak" as detected by the presence of increased plasma albumin and transferrin in lavage fluid. These changes were reversible, as shown at repeat lavage in four subjects two weeks after oxygen administration. Hyperoxia for an average of 17 hours did not change the total number or type of lung inflammatory and immune effector cells recovered by lavage (P>0.05, all comparisons). However, alveolar macrophages from subjects exposed to oxygen released increased amounts of fibronectin (P<0.05) and alveolar-macrophage–derived growth factor for fibroblasts (P<0.01) — mediators thought to modulate fibroblast recruitment and proliferation in the alveolar wall. Thus, although some of the effects of exposure to 17 hours of more than 95 per cent oxygen are reversible, hyperoxia for even this short period lowers the structural or functional barriers that normally prevent alveolar-capillary "leak" and induces processes that can culminate in fibrosis of the alveolar wall. (N Engl J Med 1983; 309:878–83.)
A Phase II Study of Sequential Velcade/Thalidomide/ Dexamethasone (VTD) as Maintenance Therapy Post Single Autologous Peripheral Stem Cell (PSCT) in Patients with Multiple Myeloma.
Authors: Firoozeh Sahebi, Amrita Krishnan, George Somlo, Leslie Popplewell, P. Parker, Ji-Lian Cai, Len Farol, Ricardo Spielberger, Neil Martin Kogut, Chatchada Karanes, Christopher Ruel, Paul Frankel, Fermin Arceo, Lupe Duarte, Margaret O'Donnell, Stephen J Forman
Journal: Blood (2009)
Hematopoietic Chimerism in Patients with Hematological Malignancies Treated with Donor Lymphocyte Infusions Combined with IL-2 for Relapse after Allogeneic Stem Cell Transplantation.
Authors: Irina Demidova, Eugenia Zhelnova, Larisa Mendeleeva, Lidia Liubimova, Andrei Misiurin, Elena Parovichnikova, Valeri Savchenko
Journal: Blood (2007)
Functional Diversity of Single Stem Cell Clones in Patients' Acute Lymphoblastic Leukemia Growing in Mice: An Adverse Subclone with Distinct DNA-Methylation Pattern, Slow Growth In Vivo and Drug Resistance
Authors: Cornelia Finkenzeller, Michela Carlet, Sebastian Vosberg, Philipp A. Greif, Irmela Jeremias
Journal: Blood (2015)
Effective Risk-Adapted Therapy for Childhood B-Precursor Acute Lymphoblastic Leukemia (ALL) with the Japan Association of Childhood Leukemia Study (JACLS) ALL-97 Protocol.
Authors: Keizo Horibe, Tooru Kudoh, Hiroki Hori, Shinichiro Nishimura, Megumi Oda, Makoto Yoshida, Yoshihiro Komada, Junichi Hara, Akio Tawa, Ikuya Usami, Akihiko Tanizawa, Keiko Yumura-Yagi
Journal: Blood (2006)
The RegiSONIC disease registry: Preliminary effectiveness and safety in the first 66 newly diagnosed locally advanced basal cell carcinoma (BCC) patients treated with vismodegib.
Authors: Mario E. Lacouture, Jean Y. Tang, Gary S. Rogers, Thomas Olencki, Ragini Reiney Kudchadkar, Simon S. Yoo, Julie Guillen, Yong Mun, Keith Lamont Dawson, Aleksandar Sekulic
Journal: Journal of Clinical Oncology (2015)

9023 Background: Treatment of advanced BCC (aBCC), including metastatic or locally advanced (la) BCC, is challenging, with approaches ranging from surgery to recently approved targeted Hedgehog pathway inhibitor vismodegib (VISMO). RegiSONIC (NCT01604252) is an ongoing, multicenter prospective observational cohort study designed to collect real-world data on the diagnosis and treatment of patients (pts) with aBCC and/or BCC nevus syndrome (BCCNS). Here we present preliminary effectiveness and safety results in the first 66 non-BCCNS newly diagnosed laBCC pts treated with VISMO. Methods: Pts are enrolling into 3 cohorts (C): newly diagnosed (VISMO-naive) aBCC pts (C1), aBCC pts who previously received VISMO in a Genentech-sponsored study (C2), or pts with BCCNS who have aBCC or multiple BCCs of any stage (C3). Determinations of disease response were investigator assessed. Pt follow-up is every ~3 months. Results: By Sept 12, 2014, 285 non-BCCNS newly diagnosed laBCC pts had been enrolled: median age, 68 years; male, 63%. 66 (23%) pts were treated with VISMO (received VISMO within 90 days of determination of laBCC). Median (range) of follow-up: 13.2 (0.16-26.8) months. Results are in the Table. All AEs leading to treatment discontinuation and 1 SAE (acute renal failure) were considered related to VISMO; the 4 deaths (6%) were not. Conclusions: Preliminary data from the RegiSONIC study demonstrate effectiveness of VISMO in non-BCCNS newly diagnosed laBCC pts, with a safety profile consistent with previous studies. Real-world data may provide clinical insights to improve the treatment of aBCC pts. Clinical trial information: NCT01604252. non-BCCNS Newly Diagnosed, VISMO-Treated laBCC Pts n = 66 Objective response rate, % (95% CI) 68 (56-79) Complete response, n (%) 29 (44) Partial response, n (%) 16 (24) Duration of response (univariate), months, median (range) 5.95 (0.03-22.08) Progression-free survival, median NE Overall survival, median NE AEs, n (%) 53 (80) Ageusia/dysgeusia, % 56 Muscle spasms, % 48 Alopecia, % 38 Weight loss, % 20 Serious AEs, n (%) 8 (12) AEs leading to discontinuation, n (%) 9 (14) Muscle spasms, % 56 Alopecia, % 44 Ageusia/dysgeusia, % 33