tbuckley/cabot-search huggingface dataset:
The adjuvant PANTHER study: A randomized comparison between dose-dense and tailored epirubicin (E), cyclophosphamide (C) and docetaxel (D) vs. standard dose 5-fluorouracil (F), epirubicin (E), cyclophosphamide (C) and docetaxel—Health-related quality of life during ongoing therapy.
Authors: Yvonne Brandberg, Hemming Johansson, Mats Hellstrom, Theodoros Foukakis, Michael Gnant, Gunter von Minckwitz, Jonas C. S. Bergh
Journal: Journal of Clinical Oncology (2016)

1035 Background: Chemotherapy is dosed per mg/m2, which results in marked differences in inter-patient pharmacokinetics and toxicities. Tailored chemotherapy is based on dose adjustments based on individually recorded toxicities. Previous studies revealed superior survival outcomes with dose dense (DD) adjuvant regimens, but docetaxel was previously not considered suitable in a DD strategy. Health related quality of life (HRQoL) was a secondary endpoint in the Panther study. Methods: Patients with node positive breast cancer (BC), or with node negative BC > 20 mm, receptor negative (Er and Pr) Elston grade III, were randomized between tailored dose dense therapy (E 38-120 mg/m 2) C 450-1200 mg/m 2) followed by four cycles D75-100 mg/m 2) every second week (three weeks pause between EC and D), G-CSF support and prophylactic antibiotics), the ddtEC-D arm, vs. the control arm (three cycles F500 E100 C500 followed by three cycles of D100 every third week). HRQoL was evaluated using EORTC QLQ-C30 + EORTC QLQ-BR23 at baseline and at end of treatment (˜ 4 months after randomization in both arms). Results: A total of 2017 patients were randomized between February 2007 and September 2011. No statistical differences at baseline for HRQoL. Results, based on 1630 patients (81%), reveal statistical significant differences (p ≤ 0.01) between the randomization arms, favoring the control arm on 13/15 of EORTC QLQ-C30 variables at the end of treatment. For EORTC-BR23, the ddtEC-D arm scored lower on the sexual functioning and chemotherapy side effects subscales. Conclusions: The ddtEC-D arm appeared to have more negative impact on HRQoL than the control arm during therapy. An abstract presenting the results from the main Panther study is also submitted to ASCO 2016. Clinical trial information: NCT00798070 ISRCTN ISRCTN39017665.
Utilité de la capsule endoscopique pour déterminer les indications et la voie d'abord de l'entéroscopie double ballon
Authors: M Delvaux, G Gay, V Laurent, I Fassler
Journal: Endoscopy (2006)

La capsule video-endoscopique (VCE) et l'entéroscopie double ballon (EDB) permettent une exploration endoscopique complète de l'intestin grêle.
Normal and Pathologic Anatomy of the Reticular Tissue in Laboratory Mice, With a Classification and Discussion of Neoplasms
Authors: Thelma B. Dunn
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Normal and Pathologic Anatomy of the Reticular Tissue in Laboratory Mice, With a Classification and Discussion of Neoplasms Get access Thelma B. Dunn Thelma B. Dunn National Cancer Institute,3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 14, Issue 6, June 1954, Pages 1281–1433, https://doi.org/10.1093/jnci/14.6.1281 Published: 01 June 1954 Article history Received: 15 March 1954 Published: 01 June 1954
TNFR2 Stimulation Promotes Mitochondrial Fusion via Stat3- and NF-kB–Dependent Activation of OPA1 Expression
Authors: Jinliang Nan, Hengxun Hu, Yong Sun, Lianlian Zhu, Yingchao Wang, Zhiwei Zhong, Jing Zhao, Na Zhang, Ya Wang, Yaping Wang, Jian Ye, Ling Zhang, Xinyang Hu, Wei Zhu, Jian’an Wang
Journal: Circulation Research (2017)

Mitochondria are important cellular organelles and play essential roles in maintaining cell structure and function. Emerging evidence indicates that in addition to having proinflammatory and proapoptotic effects, TNFα (tumor necrosis factor α) can, under certain circumstances, promote improvements in mitochondrial integrity and function, phenomena that can be ascribed to the existence of TNFR2 (TNFα receptor 2).The present study aimed to investigate whether and how TNFR2 activation mediates the effects of TNFα on mitochondria.Freshly isolated neonatal mouse cardiac myocytes treated with shRNA targeting TNFR1 were used to study the effects of TNFR2 activation on mitochondrial function. Neonatal mouse cardiac myocytes exhibited increases in mitochondrial fusion, a change that was associated with increases in mitochondrial membrane potential, intracellular ATP levels, and oxygen consumption capacity. Importantly, TNFR2 activation-induced increases in OPA1 (optic atrophy 1) protein expression were responsible for the above enhancements, and these changes could be attenuated using siRNA targeting OPA1. Moreover, both Stat3 and RelA bound to the promoter region of OPA1 and their interactions synergistically upregulated OPA1 expression at the transcriptional level. Stat3 acetylation at lysine 370 or lysine 383 played a key role in the ability of Stat3 to form a supercomplex with RelA. Meanwhile, p300 modulated Stat3 acetylation in HEK293T (human embryonic kidney 293T) cells, and p300-mediated Stat3/RelA interactions played an indispensable role in OPA1 upregulation. Finally, TNFR2 activation exerted beneficial effects on OPA1 expression in an in vivo transverse aortic constriction model, whereby TNFR1-knockout mice exhibited better outcomes than in mice with both TNFR1 and TNFR2 knocked out.TNFR2 activation protects cardiac myocytes against stress by upregulating OPA1 expression. This process was facilitated by p300-mediated Stat3 acetylation and Stat3/RelA interactions, leading to improvements in mitochondrial morphology and function.
Amlexanox Downregulates S100A6 to Sensitize <i>KMT2A/AFF1</i>-Positive Acute Lymphoblastic Leukemia to TNFα Treatment
Authors: Hayato Tamai, Hiroki Yamaguchi, Koichi Miyake, Miyuki Takatori, Tomoaki Kitano, Satoshi Yamanaka, Syunsuke Yui, Keiko Fukunaga, Kazutaka Nakayama, Koiti Inokuchi
Journal: Cancer Research (2017)

Acute lymphoblastic leukemias (ALL) positive for KMT2A/AFF1 (MLL/AF4) translocation, which constitute 60% of all infant ALL cases, have a poor prognosis even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This poor prognosis is due to one of two factors, either resistance to TNFα, which mediates a graft-versus-leukemia (GVL) response after allo-HSCT, or immune resistance due to upregulated expression of the immune escape factor S100A6. Here, we report an immune stimulatory effect against KMT2A/AFF1-positive ALL cells by treatment with the anti-allergy drug amlexanox, which we found to inhibit S100A6 expression in the presence of TNF-α. In KMT2A/AFF1-positive transgenic (Tg) mice, amlexanox enhanced tumor immunity and lowered the penetrance of leukemia development. Similarly, in a NOD/SCID mouse model of human KMT2A/AFF1-positive ALL, amlexanox broadened GVL responses and extended survival. Our findings show how amlexanox degrades the resistance of KMT2A/AFF1-positive ALL to TNFα by downregulating S100A6 expression, with immediate potential implications for improving clinical management of KMT2A/AFF1-positive ALL. Cancer Res; 77(16); 4426-33. ©2017 AACR.
Cooperativity of imprinted genes inactivated by acquired chromosome 20q deletions
Authors: Athar Aziz, E. Joanna Baxter, Carol Edwards, Clara Yujing Cheong, Mitsuteru Ito, Anthony Bench, Rebecca Kelley, Yvonne Silber, Philip A. Beer, Keefe Chng, Marilyn B. Renfree, Kirsten McEwen, Dionne Gray, Jyoti Nangalia, Ghulam J. Mufti, Eva Hellstrom-Lindberg, Jean-Jacques Kiladjian, Mary Frances McMullin, Peter J. Campbell, Anne C. Ferguson-Smith, Anthony R. Green
Journal: Journal of Clinical Investigation (2013)

Large regions of recurrent genomic loss are common in cancers; however, with a few well-characterized exceptions, how they contribute to tumor pathogenesis remains largely obscure. Here we identified primate-restricted imprinting of a gene cluster on chromosome 20 in the region commonly deleted in chronic myeloid malignancies. We showed that a single heterozygous 20q deletion consistently resulted in the complete loss of expression of the imprinted genes L3MBTL1 and SGK2, indicative of a pathogenetic role for loss of the active paternally inherited locus. Concomitant loss of both L3MBTL1 and SGK2 dysregulated erythropoiesis and megakaryopoiesis, 2 lineages commonly affected in chronic myeloid malignancies, with distinct consequences in each lineage. We demonstrated that L3MBTL1 and SGK2 collaborated in the transcriptional regulation of MYC by influencing different aspects of chromatin structure. L3MBTL1 is known to regulate nucleosomal compaction, and we here showed that SGK2 inactivated BRG1, a key ATP-dependent helicase within the SWI/SNF complex that regulates nucleosomal positioning. These results demonstrate a link between an imprinted gene cluster and malignancy, reveal a new pathogenetic mechanism associated with acquired regions of genomic loss, and underline the complex molecular and cellular consequences of "simple" cancer-associated chromosome deletions.
Unmanipulated Graft Haploindentical Allogeneic Stem Cell Transplantation (Haplo-SCT) In Acute Leukemia: A Long-Term Follow-Up Survey On Behalf Of The Acute Leukemia Working Party (ALWP) Of The European Group For Blood and Marrow Transplantation (EBMT)
Authors: Simona Piemontese, Fabio Ciceri, Myriam Labopin, Norbert Claude Gorin, He Huang, Paolo Di Bartolomeo, Depei Wu, Dietrich Beelen, Yener Koc, Boris V Afanasyev, Andrea Bacigalupo, Johanna Tischer, William Arcese, Mohamad Mohty
Journal: Blood (2013)
18F-FDG Uptake in Benign Fibrous Histiocytoma of Adrenal Gland
Authors: Teik Hin Tan, Christina Nye Bing Lai
Journal: Clinical Nuclear Medicine (2017)

A 47-year-old man with newly diagnosed nasopharyngeal carcinoma underwent staging F-FDG PET/CT. Apart from showing increased FDG uptake in the primary site and locoregional nodal and liver metastases, an unusual site of intense FDG focus was demonstrated in the left adrenal gland. He underwent CT-guided biopsy, and the histopathologic diagnosis was benign fibrous histiocytoma.
Meta-analysis of the effects on safety of front-loading (FL), every-2-week (Q2W), and Q3W dosing of darbepoetin alfa (DA) in patients (pts) with chemotherapy-induced anemia (CIA).
Authors: John A. Glaspy, Dusan Kotasek, Jean-Luc Canon, Dianne Tomita, Helen Collins, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2012)

e19511 Background: Several studies evaluated if alternate dosing could decrease the time to hemoglobin (Hb) response. With recent safety concerns, this is now of limited interest; however, these studies may contribute to the understanding of safety risks. This study-level meta-analysis examined effects of FL, Q2W, and Q3W dosing of DA vs epoetin alfa (EA) and weekly DA dosing on safety in pts with CIA. Methods: Data from 11 studies (4 FL, 5 Q2W, 1 Q3W, 1 Q2W/Q3W) conducted between 1999 and 2006 in which the comparison group received 3-times-per-week (TIW) or once-weekly (QW) EA or QW DA were included in the meta-analysis. FL dosing differed between the studies and was defined as DA 4.5 mcg/kg or 300 mg QW for 4 or 5 weeks or until Hb &gt; 12 g/dL followed by either DA 4.5 mcg/kg Q3W or a lower QW dose. Endpoints included deaths on study; disease progression (PD); embolic, thrombotic, and thromboembolic events; and rapid Hb rise (1 g/dL within 14 days). Random effects odds ratios (ORs) are provided comparing FL, Q2W, or Q3W arms to either TIW or QW active control arms. Heterogeneity was assessed using I 2 statistic. Results: No differences in ORs for death, PD, embolic, thrombotic, and thromboembolic events or evidence of a more rapid rate of Hb rise were observed in FL, Q2W, and Q3W arms compared with controls (table). Conclusions: Results of this meta-analysis suggested that these adverse events were not related to FL, Q2W, or Q3W dosing of DA. [Table: see text]
Landscape scanning of cancer gene panels: A report from the NIH Genetic Testing Registry (GTR).
Authors: Wendy S. Rubinstein, Adriana J. Malheiro, Brandi L. Kattman, Baoshan Gu, Vichet Hem, Kenneth S. Katz, Michael Ovetsky, Guangfeng Song, Ricardo Villamarin-Salomon, Craig Wallin, Donna R. Maglott, Jennifer M. Lee
Journal: Journal of Clinical Oncology (2016)

e13120 Background: Genetic testing of tumors and germlines has proliferated in oncology, as gauged by ASCO’s meeting topics and the medical literature. A quantitative appraisal of orderable genetic tests over recent years can provide insight into the evolution of oncology practice. GTR (https://www.ncbi.nlm.nih.gov/gtr/) is a freely available web resource created to enable centralized access to comprehensive information about genetic tests and improve transparency. GTR panel analyses were used by AMA to help create new CPT codes and by CDC to prioritize the development of next-generation sequencing (NGS) reference materials. Methods: We compared GTR content available February 2014, 2015 and 2016 by querying the GTR database for lab and test attributes such as methods, genes, and indications. We defined a gene panel as having > 4 targets and a commonly tested gene as being in > 99 tests. Comprehensive GTR data can be downloaded in XML format using FTP or E-Utilities. Results: As of 2/1/16, GTR has 32,969 tests for 5,996 conditions offered by 462 labs in 41 countries, a 138% increase in test count over 24 months. GTR’s oncology subset has 5,568 tests for neoplasms, hereditary cancer syndromes and pharmacogenetics, representing 17% of current GTR tests and reflecting a 153% increase in the oncology subset over the past 12 months. Cancer genes comprise 36% (29/80) of the most commonly tested genes. 622 tests have somatic targets. NGS methodology rose from 10% of molecular tests to 27% over 24 months. Of the 8,438 NGS tests, 79% report out only a single gene result. 98% of these NGS ‘single gene tests’ are from 20 labs. Panels comprise 16.4% (1,380) of NGS tests. GTR has 156 NGS cancer gene panels with 5 to 112 genes. Conclusions: Cancer genes, panels, and NGS feature prominently in laboratory test offerings. A new phenomenon is the ability to selectively order 1 or more genes performed as part of a much larger NGS assay. The ordering clinician can thereby avoid reporting of markers that may be added to improve sensitivity but have unclear validity or utility. As community-based recruitment grows for genomic oncology trials (eg, TAPUR), genetic tests ordered by clinical oncologists can be captured as an element of trial methods using GTR’s structured data.
Abstract P063: Vitamin D and Parathyroid Hormone are Cross-sectionally Associated with Higher Levels of B-type Natriuretic Peptide: The Hoorn Study
Authors: Adriana van Ballegooijen, Marjolein Visser, Marieke B Snijder, Jacqueline M Dekker, Giel Nijpels, Coen D Stehouwer, Michaela Diamant, Ingeborg A Brouwer
Journal: Circulation (2012)

Background: Low serum 25-hydroxyvitamin D (25OHD) levels have been associated with increased risk of cardiovascular disease. Dysfunction of the vitamin D-parathyroid hormone (PTH)-calcium axis may play a role in the pathogenesis of heart failure. Hypothesis: We investigated whether lower serum 25OHD levels and higher PTH levels are associated with higher B-type natriuretic peptide (BNP) levels in older individuals both cross-sectionally and after 8 years of follow-up. Methods: We measured baseline serum 25OHD, PTH and BNP in 502 subjects in 2000–2001 in the Hoorn Study, a population-based cohort. Follow-up BNP was measured in 2007–2009 in 278 subjects. Subjects were categorized according to season and sex-specific 25OHD and PTH quartiles at baseline. We studied the association of 25OHD and PTH quartiles with BNP using linear regression analyses adjusting for confounders. Effect-modification by kidney function and CVD presence was examined. Results: Subjects had a mean age of 70 years, mean 25OHD level of 52±19.5 (nmol/L) and mean PTH of 6.1±2.4 (pmol/L). The lowest 25-OHD quartile was cross-sectionally associated with higher BNP, in subjects with low kidney function only (eGFR&lt;77.3 mL/min/1.73m 2 )(=sample median). The association attenuated after adjustment for PTH. PTH was cross-sectionally associated with BNP in subjects with low kidney function only (p-for-trend &lt; 0.05), even after adjustment for 25OHD (Figure 1). Neither 25OHD nor PTH was associated with BNP in longitudinal analyses. Conclusion: This study showed no strong association between 25OHD and BNP. However, PTH - a potential mediator in the relation between 25OHD and BNP, was associated with BNP in subjects with low kidney function.
T-DM1 activity in metastatic HER2-positive breast cancers that received prior therapy with trastuzumab and pertuzumab.
Authors: Hannah Elizabeth Dzimitrowicz, Michael J. Berger, Craig Vargo, Annette Hood, Osama Abdelghany, Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, Lajos Pusztai, Rashmi Krishna Murthy
Journal: Journal of Clinical Oncology (2016)

585 Background: Ado-trastuzumab emtansine (T-DM1) is currently approved for patients with trastuzumab-resistant HER2-positive metastatic breast cancer (MBC). However, there is no data on the activity of T-DM1 in patients who received prior pertuzumab, now included as standard first line therapy. The goal of this study was to assess the efficacy of T-DM1 in routine clinical practice in a contemporary patient population that received prior trastuzumab and pertuzumab. Methods: We identified all patients with HER2-positive MBC who received T-DM1 after trastuzumab and pertuzumab between March 1, 2013 and July 15, 2015 through electronic pharmacy records and departmental databases at 3 institutions, MD Anderson Cancer Center, Smilow Cancer Hospital at Yale and The James Cancer Hospital at the Ohio State University. We reviewed the medical records of each case to confirm treatment sequencing and outcome. Results: Eighty-two patients were identified and 78 were available for outcome analysis; 32% received T-DM1 as 1st/2nd line therapy and 48% received it as > 4th line treatment. Response rate was 17.9% (95% CI, 9.4-26.4%). Median duration on therapy was 4.0 months (95% CI, 2.7-5.1, range: 0-22.5). Clinical benefit rate (CBR), defined as complete or partial response or treatment duration > 6 months, was 37.2% (95% CI, 26.5-47.9%). T-DM1 was discontinued for disease progression in 84% of patients and for toxicity in 10%. Conclusions: Tumor response rates were lower than prior reports in trastuzumab-resistant HER2-positive MBC, but one third of patients received T-DM1 for > 6 months which suggests clinically relevant benefit to T-DM1 in patients who received prior pertuzumab. Physician designated tumor response rate (ORR). Characteristic No. of Patients % 95% CI All Patients 78 ORR 14 17.9 9.4 to 26.4 Hormone Receptor Status ER and/or PR-positive 49 ORR 10 20.4 9.1 to 31.7 ER and PR-negative 29 ORR 4 13.8 1.3 to 26.4 T-DM1 as 2nd Line Therapy 26 ORR 6 23.1 6.9 to 39.3 T-DM1 as > 2nd Line Therapy 52 ORR 8 15.4 5.6 to 25.2 Recurrence Free Interval De Novo Metastatic Disease 33 ORR 7 21.2 7.3 to 35.2 Met. Recurrence < 1 year after diagnosis 14 ORR 3 21.4 0 to 42.9 Met. Recurrence > 1 year after diagnosis 31 ORR 4 12.9 1.1 to 24.7
89Zr-lumretuzumab PET imaging before and during HER3 antibody lumretuzumab treatment of solid tumor patients.
Authors: Frederike Bensch, Laetitia E. Lamberts, Michiel M. Smeenk, Annelies Jorritsma-Smit, Marjolijn N. Lub-de Hooge, Anton G.T. Terwisscha van Scheltinga, Johan R. de Jong, Jourik A. Gietema, Carolina Pia Schroder, Marlene Thomas, Wolfgang Jacob, Keelara Abiraj, Celine Adessi, Georgina Meneses-Lorente, Ian James, Martin Weisser, Adrienne H. Brouwers, Elisabeth De Vries
Journal: Journal of Clinical Oncology (2016)

11555 Background: Lumretuzumab is a humanized, glycoengineered, monoclonal antibody targeting human epidermal growth factor receptor 3 (HER3), in phase Ib clinical development in patients with HER3-positive solid tumors. We performed a PET imaging study with 89Zr-lumretuzumab to demonstrate tumor targeting and support dose selection by evaluating the dose required for target saturation. Methods: Thirteen patients with HER3-positive metastatic or locally advanced solid tumors were imaged at baseline with PET 4 and 7 days after receiving 37 MBq 89Zr-lumretuzumab, along with a previously determined imaging protein dose of 100 mg unlabeled lumretuzumab. After 2 weeks, imaging was repeated using the PD-active dose of 400, 800 or 1600 mg unlabeled lumretuzumab combined with 89Zr-lumretuzumab. Normal organ and tumor uptake were calculated as standardized uptake values (SUV). Results: 59 out of 109 lesions (54%) with a size of ≥ 10 mm were quantifiable on baseline PET scans. 39 (36%) showed no visible tracer uptake and 11 (10%) were not quantifiable due to high background. In all patients except one, tracer uptake was measurable in ≥ 1 tumor lesion. At baseline, mean tumor SUVmax was 3.2 (±1.8) at 4 days postinjection, with a 6-fold difference in mean tumor tracer uptake between patients. Tumor uptake after the first PD-active dose was evaluable for 7/13 patients and decreased by 11.9% (±8.2), 10.0% (±16.5) and 24.6% (±20.9) after administration of 400, 800 and 1600 mg unlabeled lumretuzumab, respectively. SUVmean for normal blood, liver and lung were respectively 4.8, 6.4 and 0.9 on the baseline scan 4 days postinjection and was not affected by the first PD-active dose. Conclusions: 89Zr-PET imaging showed tumor targeting with lumretuzumab in all but 1 patient. Tumor uptake decreased at the 400 mg dose level, but no plateau was reached with increasing doses. Previous phase I data demonstrated linear serum PK and HER3 down regulation at doses of ≥ 400 mg (Meulendijks et al., CCR 2015). The reason for these discrepant results could be multifaceted, highlighting the need for additional quantitative assessment to understand further the link between SUV, serum PK and distribution of lumretuzumab into various tumor lesions. Clinical trial information: NCT01482377.