tbuckley/cabot-search huggingface dataset:
Prospective evaluation of the diagnostic value of sensitive <i><scp>KIT</scp></i> D816V mutation analysis of blood in adults with suspected systemic mastocytosis
Authors: T. Kristensen, H. Vestergaard, C. Bindslev‐Jensen, C. G. Mortz, H. F. Kjaer, M. Ollert, M. B. Møller, S. Broesby‐Olsen
Journal: Allergy (2017)

Sensitive KIT D816V mutation analysis of blood has been proposed to guide bone marrow (BM) investigation in suspected systemic mastocytosis (SM). The aim of this prospective study was for the first time to compare the D816V status of the "screening blood sample" used to guide BM biopsy in suspected SM to the outcome of the subsequent BM investigation.Fifty-eight adult patients with suspected SM were included. The outcome of sensitive KIT D816V analysis of blood was compared to the result of the BM investigation.Screening blood samples from 44 of 58 patients tested D816V-positive. In 43 of these, SM was subsequently diagnosed in the BM investigation. One patient with a D816V-positive screening sample was diagnosed with monoclonal MC activation syndrome. Screening blood samples from 14 patients tested D816V-negative. SM was subsequently diagnosed in five of these, whereas nine patients did not fulfill any diagnostic SM criteria (excluding tryptase criterion). Of the 48 SM patients, 90% tested D816V-positive. Thirteen SM patients presented with Hymenoptera venom-induced anaphylaxis, no skin lesions, and baseline serum tryptase ≤20 ng/mL. Of these, 92% tested D816V-positive in the screening blood sample.This prospective study demonstrates that a D816V-positive result in a screening blood sample identifies SM among patients with hymenoptera venom-induced anaphylaxis in whom the diagnosis would most probably have been missed, with potential severe implications. The observed false-negative screening results also underline that BM investigation is mandatory in all adult patients with clear signs of, or highly suspected SM, regardless of the KIT mutation status.
Interaction between Tumor Cell Surface Receptor RAGE and Proteinase 3 Mediates Prostate Cancer Metastasis to Bone
Authors: Mikhail G. Kolonin, Anna Sergeeva, Daniela I. Staquicini, Tracey L. Smith, Christy A. Tarleton, Jeffrey J. Molldrem, Richard L. Sidman, Serena Marchiò, Renata Pasqualini, Wadih Arap
Journal: Cancer Research (2017)

Human prostate cancer often metastasizes to bone, but the biological basis for such site-specific tropism remains largely unresolved. Recent work led us to hypothesize that this tropism may reflect pathogenic interactions between RAGE, a cell surface receptor expressed on malignant cells in advanced prostate cancer, and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and hematopoietic cells within the bone marrow microenvironment. In this study, we establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to the bone marrow. PR3 bound to RAGE on the surface of prostate cancer cells in vitro, inducing tumor cell motility through a nonproteolytic signal transduction cascade involving activation and phosphorylation of ERK1/2 and JNK1. In preclinical models of experimental metastasis, ectopic expression of RAGE on human prostate cancer cells was sufficient to promote bone marrow homing within a short timeframe. Our findings demonstrate how RAGE-PR3 interactions between human prostate cancer cells and the bone marrow microenvironment mediate bone metastasis during prostate cancer progression, with potential implications for prognosis and therapeutic intervention. Cancer Res; 77(12); 3144-50. ©2017 AACR.
Overexpressed K+ channels in cisplatin resistant cells influence resistance variably in different cell types
Authors: Xing-Jie Liang, Barbara Taylor, Carol Cardelli, Jun-Jie Yin, Susan H. Garfield, Stephen Wincovitch, Adorjan Aszalos, Michael M. Gottesman
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1489 

Altered potassium fluxes have been previously associated with cisplatin resistance ( Thompson et al., Cancer 54:1269,1984; Marklund et al ., Int. J. Cancer 93:577, 2001). Our interest focused on detection of overexpression of K+ channels on cisplatin resistant cells and their functional relation to cisplatin resistance. In our studies, we used two series of cells with increasing resistance to cisplatin, the human epidermal KB and human liver BEL-7404 carcinoma cell lines. We showed by confocal microscopy that K+ channels are increased in parallel with increasing cisplatin resistance. With increasing cisplatin resistance the plasma membrane potential also increases. In order to study the influence of the overexpressed K+ channels and the altered ion homeostasis in the resistant cells, we have conducted cell proliferation studies in the presence of antibodies against the K+channels, omeprazole, the H+ pump inhibitor, and a specific inhibitor of the ether-a-gogo gene expressed K+channel, WAY-123398-A-5. The antibodies and omeprazole influenced cell growth and cisplatin resistance only very slightly. The specific K+ channel blocker did not alter cisplatin resistance in these two cell lines. We have also observed that manipulation of K+ fluxes with antibodies or the H+pumps with omeprazole results in opposite effect, increase or decrease of cisplatin resistance, in these two cell lines. We have concluded that cisplatin resistance is only slightly related to the ion homeostasis of cells and that the connection is cell specific.
Long-Lasting Response to Nivolumab and Immune-Related Adverse Events in a Nonsquamous Metastatic Non–Small Cell Lung Cancer Patient
Authors: Biagio Ricciuti, Giulio Metro, Sara Baglivo, Daniela Colabrese, Rita Chiari, Chiara Bennati, Luca Paglialunga
Journal: Journal of Thoracic Oncology (2017)
Single high sensitivity troponin test can rule out MI, evidence confirms
Authors: Jacqui Wise
Journal: BMJ (2017)

The use of a single high sensitivity troponin T test to rule out myocardial infarction (MI) quickly and safely in patients presenting to emergency departments with possible emergency acute coronary syndrome is supported by a meta-analysis reported in the Annals of Internal Medicine .1

In December 2016 new guidance from the National Institute for Health and Care Excellence stated that patients presenting with acute chest pain …
Nilotinib in chronic myeloid leukemia patients in chronic phase (CML-CP) with imatinib (IM) resistance or intolerance: Longer follow-up results of a phase II study
Authors: H. Kantarjian, F. Giles, K. Bhalla, J. Pinilla, R. A. Larson, N. Gattermann, O. G. Ottmann, N. J. Gallagher, M. Baccarani, P. leCoutre
Journal: Journal of Clinical Oncology (2009)

7029 Background: Nilotinib is a potent and highly selective BCR-ABL inhibitor approved for the treatment of Ph+ CML patients (pts) in CP or accelerated phase who are resistant or intolerant to prior therapy including IM. This study evaluated the efficacy and safety of nilotinib (400 mg bid) in CML-CP pts resistant or intolerant to IM. Methods: Primary endpoint was major cytogenetic response (MCyR). Secondary endpoints included complete cytogenetic response (CCyR), complete hematological response (CHR), MCyR duration, overall survival (OS), and safety. Results: CML-CP pts (n = 321, 70% IM-resistant, 30% IM-intolerant with resistance) with a minimum follow-up of 19 months (mos) were evaluated; 72% were treated with ≥600 mg/day IM prior to enrollment. Median duration of prior IM treatment was 32 (&lt;1–94) mos. Median dose intensity of nilotinib (790 mg/day; range 151–1,110 mg/day) closely approximated the planned dose. Nilotinib led to rapid and durable CHR and MCyR. CHR was observed in 94% of pts. 59% achieved an MCyR (2.8 mos median time to MCyR; 56% in IM-resistant, and 65% in IM-intolerant pts), including 73% of pts with a baseline CHR and 44% achieved a CCyR (41% in IM-resistant; 51% in IM-intolerant pts). Responses were durable, with 78% pts maintaining MCyR at 24 mos. Estimated OS rate was 88% at 24 mos. Safety profile did not change with longer follow-up. Most frequent grade (gr) 3/4 biochemical laboratory abnormalities were elevated lipase (17%), hypophosphataemia (16%), hyperglycemia (12%), and total bilirubin (8%) which were transient and clinically asymptomatic. Gr 3/4 non-hematologic AEs were infrequent: rash, headache, and diarrhea occurred in 2% of pts. Most common gr 3/4 hematological laboratory abnormalities were neutropenia (31%), thrombocytopenia (31%), and anemia (10%). Brief dose interruptions were successful in management of most AEs. Pleural or pericardial effusions (gr 3/4) were uncommon (&lt; 1%). Conclusions: These results demonstrate that nilotinib was highly effective, with rapid and durable responses in CML-CP pts failing prior therapy due to resistance or intolerance. Nilotinib was well tolerated with favorable risk/benefit. [Table: see text]
Germline Mutations in the Kallikrein 6 Region and Predisposition for Aggressive Prostate Cancer
Authors: Laurent Briollais, Hilmi Ozcelik, Jingxiong Xu, Maciej Kwiatkowski, Emilie Lalonde, Dorota H. Sendorek, Neil E. Fleshner, Franz Recker, Cynthia Kuk, Ekaterina Olkhov-Mitsel, Sevtap Savas, Sally Hanna, Tristan Juvet, Geoffrey A. Hunter, Matt Friedlander, Hong Li, Karen Chadwick, Ioannis Prassas, Antoninus Soosaipillai, Marco Randazzo, John Trachtenberg, Ants Toi, Yu-Jia Shiah, Michael Fraser, Theodorus van der Kwast, Robert G. Bristow, Bharati Bapat, Eleftherios P. Diamandis, Paul C. Boutros, Alexandre R. Zlotta
Journal: JNCI Journal of the National Cancer Institute (2016)

There is a need for markers that can specifically identify individuals at increased risk of harboring aggressive forms of prostate cancer (PCa).We surveyed the Kallikrein ( KLK ) region ( KLK 1-15) for single-nucleotide polymorphisms (SNPs) associated with aggressive PCa (Gleason Score ≥ 8) in 1858 PCa patients. Discovery cohorts (Swiss arm of the European Randomized Study of Screening for PCa, n = 379; Toronto, Canada, n = 540) and a validation cohort (Prostate, Lung, Colorectal and Ovarian [PLCO] screening trial, n = 939) were analyzed. Fine-mapping within the KLK region was carried out by genotyping and imputation in the discovery cohort, whereas PLCO data were provided through database of Genotypes and Phenotypes ( dbGaP ). The influence of SNPs of interest on biochemical-free survival was evaluated in a cohort of localized PCa from the International Cancer Genome Consortium (ICGC; n = 130) analyzed with next-generation sequencing. Single- and multi-SNP association studies, as well as haplotype analyses, were performed. All statistical tests were two-sided.Several SNPs in very strong linkage disequilibrium in the KLK 6 region and located within the same haplotype (rs113640578, rs79324425, rs11666929, rs28384475, rs3810287), identified individuals at increased risk of aggressive PCa in both discovery (odds ratio [OR] = 3.51-3.64, 95% confidence interval [CI] = 2.01 to 6.36, P = 1.0x10 -5 -8.4x10 -6 ) and validation (OR = 1.89-1.96, 95% CI = 0.99 to 3.71, P = .04-.05) cohorts. The overall test of haplotype association was highly statistically significant in each cohort ( P = 3.5x10 -4 and .006, respectively) and in the three data sets combined ( P = 2.3x10 -5 ). These germline SNPs independently predicted relapse in the ICGC cohort (hazard ratio = 3.15, 95% CI = 1.57 to 6.34, P = .001).Our fine-mapping study has identified novel loci in the KLK 6 region strongly associated with aggressive PCa.
Accuracy of PECARN, CATCH, and CHALICE head injury decision rules in children: a prospective cohort study
Authors: Franz E Babl, Meredith L Borland, Natalie Phillips, Amit Kochar, Sarah Dalton, Mary McCaskill, John A Cheek, Yuri Gilhotra, Jeremy Furyk, Jocelyn Neutze, Mark D Lyttle, Silvia Bressan, Susan Donath, Charlotte Molesworth, Kim Jachno, Brenton Ward, Amanda Williams, Amy Baylis, Louise Crowe, Ed Oakley, Stuart R Dalziel
Journal: The Lancet (2017)
Long Term Follow up After Hematopoietic Stem Cell Transplantation for Fanconi Anemia: Analysis of 126 Pts Surviving More Than 2 Years After Transplant.
Authors: Carmem Bonfim, Lisandro L Ribeiro, Marco Bitencourt, Gisele Loth, Daniela Pilonetto, Neiva Magdalena, Mariester Malvezzi, Ricardo Pasquini
Journal: Blood (2012)
Hypoxic adaptation of leukemic cells infiltrating the CNS affords a therapeutic strategy targeting VEGFA
Authors: Itaru Kato, Yoko Nishinaka, Masahiro Nakamura, Ayse U. Akarca, Akira Niwa, Hiroki Ozawa, Kenichi Yoshida, Makiko Mori, Dapeng Wang, Makiko Morita, Hiroo Ueno, Yusuke Shiozawa, Yuichi Shiraishi, Satoru Miyano, Rajeev Gupta, Katsutsugu Umeda, Kenichiro Watanabe, Katsuyoshi Koh, Souichi Adachi, Toshio Heike, Megumu K. Saito, Masashi Sanada, Seishi Ogawa, Teresa Marafioti, Akira Watanabe, Tatsutoshi Nakahata, Tariq Enver
Journal: Blood (2017)
Uncommon Hematologic Malignancies
Authors: Thein H. Oo, Leo S. Aish, Douglas Schneider, Paul J. Hesketh
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.02.094 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 14615456 Uncommon Hematologic Malignancies CASE 2. CALCIFICATION IN UNTREATED PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA WITH SCLEROSIS Thein H. OoxThein H. OoSearch for articles by this author , Leo S. AishxLeo S. AishSearch for articles by this author , Douglas SchneiderxDouglas SchneiderSearch for articles by this author , Paul J. HeskethxPaul J. HeskethSearch for articles by this author Show More Caritas St. Elizabeth’s Medical Center of Boston, Tufts University School of Medicine, Boston, MA https://doi.org/10.1200/JCO.2003.02.094 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
A Squalene-Based Nanomedicine for Oral Treatment of Colon Cancer
Authors: Larissa Kotelevets, Eric Chastre, Joachim Caron, Julie Mougin, Gerard Bastian, Alain Pineau, Francine Walker, Therese Lehy, Didier Desmaële, Patrick Couvreur
Journal: Cancer Research (2017)

Nanotechnology offers many possibilities to improve drug treatments, including with regard to drug pharmacology. The current study reports a simple approach to improve cisplatin efficacy in the treatment of colon cancer through the creation of orally administered squalenoylated nanoparticles loaded with cisplatin (SQ-CDDP NP). Cytotoxic effects of SQ-CDDP NP were assessed in human colonic cells and in mouse models of intestinal cancer. In cell culture, SQ-CDDP NP exhibited at least 10-fold greater cytotoxic potency compared with uncomplexed cisplatin, reflecting an enhancement in intracellular accumulation and DNA platination. Mechanistic investigations showed that SQ-CDDP NP stimulated ROS production, expression of heavy metal-inducible and stress-inducible genes, stress kinase cascades, and apoptosis. In ApcMin/+ mice, a model of intestinal tumorigenesis, oral administration of SQ-CDDP NP curtailed spontaneous tumor formation and azoxymethane-induced colon carcinogenesis with no apparent evidence of tissue toxicity. Our results offer preclinical validation of a nanocarrier formulation that can safely improve chemotherapeutic efficacy, address risks of drug resistance, and improve patient compliance by enabling oral administration. Cancer Res; 77(11); 2964-75. ©2017 AACR.
Whole-genome noncoding sequence analysis in T-cell acute lymphoblastic leukemia identifies oncogene enhancer mutations
Authors: Shaoyan Hu, Maoxiang Qian, Hui Zhang, Yu Guo, Jin Yang, Xujie Zhao, Hailong He, Jun Lu, Jian Pan, Meimei Chang, Guoqing Du, Ting-Nien Lin, Shirley Kow-Yin Kham, Thuan Chong Quah, Hany Ariffin, Ah-Moy Tan, Yong Cheng, Chunliang Li, Allen Eng-Juh Yeoh, Ching-Hon Pui, Anders Jacobsen Skanderup, Jun J. Yang
Journal: Blood (2017)
Conflict in South Asia and its impact on health
Authors: Siddarth David, Rukhsana Gazi, Mohammed Shafiq Mirzazada, Chesmal Siriwardhana, Sajid Soofi, Nobhojit Roy
Journal: BMJ (2017)

Improving access to healthcare, preventing gender based violence, and providing mental health services are essential to improve the health of people affected by conflict in South Asia, argue <b>Siddarth David and colleagues</b>
Analysis of Clonal Evolution in Chronic Lymphocytic Leukemia from Inactive to Symptomatic Disease Prior Treatment Using Whole-Exome Sequencing
Authors: María Hernández-Sánchez, Lenka Radova, Jana Kotaskova, David Tamborero, Ana E Rodriguez, Karla Plevova, María Abáigar, Vasileios Bikos, Rocío Benito, Sylvia Takacova, Miguel Quijada, Ana África Martín, Miguel Alcoceba, Alfonso García de Coca, Michael Doubek, Marcos González, Nuria Lopez-Bigas, Sarka Pospisilova, Jesús María Hernández-Rivas
Journal: Blood (2016)
Vitamin C Prevents Offspring DNA Methylation Changes Associated with Maternal Smoking in Pregnancy
Authors: Lyndsey E. Shorey-Kendrick, Cindy T. McEvoy, Betsy Ferguson, Julja Burchard, Byung S. Park, Lina Gao, Brittany H. Vuylsteke, Kristin F. Milner, Cynthia D. Morris, Eliot R. Spindel
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Infants whose mothers smoked during pregnancy demonstrate lifelong decreases in pulmonary function. DNA methylation changes associated with maternal smoking during pregnancy have been described in placenta and cord blood at delivery, in fetal lung, and in buccal epithelium and blood during childhood. We demonstrated in a randomized clinical trial ( ClinicalTrials.gov identifier, NCT00632476) that vitamin C supplementation to pregnant smokers can lessen the impact of maternal smoking on offspring pulmonary function and decrease the incidence of wheeze at 1 year of age.To determine whether vitamin C supplementation reduces changes in offspring methylation in response to maternal smoking and whether methylation at specific CpGs is also associated with respiratory outcomes.Targeted bisulfite sequencing was performed with a subset of placentas, cord blood samples, and buccal samples collected during the NCT00632476 trial followed by independent validation of selected cord blood differentially methylated regions, using bisulfite amplicon sequencing.The majority (69.03%) of CpGs with at least 10% methylation difference between placebo and nonsmoker groups were restored (by at least 50%) toward nonsmoker levels with vitamin C treatment. A significant proportion of restored CpGs were associated with phenotypic outcome with greater enrichment among hypomethylated CpGs.We identified a pattern of normalization in DNA methylation by vitamin C supplementation across multiple loci. The consistency of this pattern across tissues and time suggests a systemic and persistent effect on offspring DNA methylation. Further work is necessary to determine how genome-wide changes in DNA methylation may mediate or reflect persistent effects of maternal smoking on lung function.
Lipid lowering effect of fulvestrant in hormone-sensitive metastatic breast cancer patients
Authors: A. Camerini, D. Amoroso, O. Garrone, M. Vincenti, G. Tartarelli, S. Donati, C. Valsuani, O. Siclari, V. Polla Mattiot, A. Sgambato
Journal: Journal of Clinical Oncology (2007)

1085 Background: Fulvestrant (F) is a pure anti-estrogen agent available for the HT of post-menopausal ormone-sensitive advanced breast cancer (ABC). Aim of the study is to analyze the effect(s) of F treatment on lipid profile, endometrial mucosa and coagulation indices (CI). Methods: 24 pts (mean age 66.2 ± 9.5 yrs) with hormone-sensitive ABC were enrolled. All patients (data on 21 pts) received at least one previous HT course, with 90.5% receiving =2 HT courses. Last HT was exemestane in 13/21, letrozole in 5/21 and other in 3/21 with a median withdrawal time of 19 days (range 3–1,456). All pts but one received at least one previous CT regimen, with 60% receiving =2 CT regimens. Complete fasting lipid blood profile and CI were assessed before F administration, every 3 months and at discontinuation. Endometrial mucosa thickness was evaluated before F administration and at end-study time. All patients referred no significant dietary changes during treatment. Pts receiving statins were excluded. Results: pts received a median of 6 F injections (range 3–14). We observed SD in 10/21 pts and PD in 11/21 pts with a mean TTP of 6.2 ± 2.9 months. Total cholesterol (C) levels significantly decreased during F treatment (214.1 ± 48.7 vs 194.0 ± 41.0 mg/dl; p=0.0084) together with LDL-C (119.5 ± 40.7 vs 104.2 ± 30.4 mg/dl; p=0.0067). HDL-C (62.4 ± 17.8 vs 64.3 ± 19.5 mg/dl; p = ns) and triglycerides (152.4 ± 64.5 vs 148.2 ± 61.6 mg/dl; p=ns) did not show significant changes. Subgroup analysis demonstrated a reduction in both pts receiving = 6 (n=17) or &gt;6 (n=11) injections (204.6 ± 45.3 vs 186.6 ± 41.2 mg/dl, p=0.014 and 219.5 ± 48.9 vs 203.9 ± 33.3 mg/dl, p=ns respectively). All CI and mean endometrial mucosa thickness value did not vary. Conclusions: We observed a clear lipid lowering effect of F in our study population. We suggest a possible effect of F on lipid metabolism. Lipid lowering effect of F it’s evident during the first six months of treatment lasting in pts continuing therapy. No significant financial relationships to disclose.
Association of Common Genetic Variants With Contralateral Breast Cancer Risk in the WECARE Study
Authors: Mark E. Robson, Anne S. Reiner, Jennifer D. Brooks, Patrick J. Concannon, Esther M. John, Lene Mellemkjaer, Leslie Bernstein, Kathleen E. Malone, Julia A. Knight, Charles F. Lynch, Meghan Woods, Xiaolin Liang, Robert W. Haile, David J. Duggan, Roy E. Shore, Susan A. Smith, Duncan C. Thomas, Daniel O. Stram, Jonine L. Bernstein
Journal: JNCI Journal of the National Cancer Institute (2017)

Women with unilateral breast cancer (UBC) are at risk of developing a subsequent contralateral breast cancer (CBC). Common variants are associated with breast cancer risk. Whether these influence CBC risk is unknown.Participants were breast cancer cases from the population-based Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study. Sixty-seven established breast cancer risk loci were genotyped directly or by imputation in 1459 case subjects with CBC and 2126 UBC control subjects. An unweighted polygenic risk score (PRS) was created by summing the number of risk alleles for each directly genotyped single nucleotide polymorphism (SNP), or for imputed loci, the imputed dosage. A weighted PRS was calculated similarly, but where each SNP's contribution was weighted by the published per-allele log odds ratio. Unweighted and weighted polygenic risk scores and CBC risk were modeled using conditional logistic regression. Cumulative CBC risk was estimated and benchmarked using Surveillance, Epidemiology, and End Results population incidence rates.Both unweighted and weighted PRS were statistically significantly associated with CBC risk. The adjusted risk ratio of CBC in women in the upper quartile of unweighted PRS compared with the lowest quartile was 1.63 (95% confidence interval [CI] = 1.33 to 2.00). The estimated 10-year cumulative risk for women in the upper quartile of the unweighted PRS was 7.4% (95% CI = 6.0% to 9.1%). For women in the upper quartile of the weighted PRS, the risk ratio for CBC was 1.75 (95% CI = 1.41 to 2.18) compared with women in the lowest quartile. There was no statistically significant heterogeneity by age, treatment (radiation therapy dose, tamoxifen, chemotherapy), estrogen receptor status of the first primary, histology of the first primary, length of at-risk period for CBC, or breast cancer family history.Common genomic variants associated with the development of first primary breast cancer are also associated with the development of CBC; the risk is strongest among those who carry more risk alleles.