tbuckley/cabot-search huggingface dataset:
Radiomics Features of Multiparametric MRI as Novel Prognostic Factors in Advanced Nasopharyngeal Carcinoma
Authors: Bin Zhang, Jie Tian, Di Dong, Dongsheng Gu, Yuhao Dong, Lu Zhang, Zhouyang Lian, Jing Liu, Xiaoning Luo, Shufang Pei, Xiaokai Mo, Wenhui Huang, Fusheng Ouyang, Baoliang Guo, Long Liang, Wenbo Chen, Changhong Liang, Shuixing Zhang
Journal: Clinical Cancer Research (2017)

Purpose: To identify MRI-based radiomics as prognostic factors in patients with advanced nasopharyngeal carcinoma (NPC).Experimental Design: One-hundred and eighteen patients (training cohort: n = 88; validation cohort: n = 30) with advanced NPC were enrolled. A total of 970 radiomics features were extracted from T2-weighted (T2-w) and contrast-enhanced T1-weighted (CET1-w) MRI. Least absolute shrinkage and selection operator (LASSO) regression was applied to select features for progression-free survival (PFS) nomograms. Nomogram discrimination and calibration were evaluated. Associations between radiomics features and clinical data were investigated using heatmaps.Results: The radiomics signatures were significantly associated with PFS. A radiomics signature derived from joint CET1-w and T2-w images showed better prognostic performance than signatures derived from CET1-w or T2-w images alone. One radiomics nomogram combined a radiomics signature from joint CET1-w and T2-w images with the TNM staging system. This nomogram showed a significant improvement over the TNM staging system in terms of evaluating PFS in the training cohort (C-index, 0.761 vs. 0.514; P < 2.68 × 10-9). Another radiomics nomogram integrated the radiomics signature with all clinical data, and thereby outperformed a nomogram based on clinical data alone (C-index, 0.776 vs. 0.649; P < 1.60 × 10-7). Calibration curves showed good agreement. Findings were confirmed in the validation cohort. Heatmaps revealed associations between radiomics features and tumor stages.Conclusions: Multiparametric MRI-based radiomics nomograms provided improved prognostic ability in advanced NPC. These results provide an illustrative example of precision medicine and may affect treatment strategies. Clin Cancer Res; 23(15); 4259-69. ©2017 AACR.
The mammalian target of rapamycin inhibitor everolimus suppresses proliferation, metabolic activity and collagen synthesis of human fibroblasts <i>in vitro</i> and exerts antifibrogenic effects <i>in vivo</i>
Authors: M. Böhm, A. Stegemann, D. Metze, K. Scharffetter-Kochanek, A. Sindrilaru
Journal: British Journal of Dermatology (2017)
Identification &amp; Characterization of Novel Hemostatic Biomarkers of Adverse Clinical Events in Patients with Continuous Flow Left Ventricular Assist Device Implants
Authors: Nathan McClane, Walter Jeske, Jeanine M. Walenga, Vicki Escalante, Erin Coglianese, Debra Hoppensteadt, Jeffrey Schwartz, Mamdouh Bakhos
Journal: Blood (2016)
Abstract P4-03-06: Microenvironmental control of breast cancer subtype elicited by paracrine growth factors signaling
Authors: M Bocci, M Bartoschek, K Pietras
Journal: Cancer Research (2017)

Abstract During cancer progression from an indolent stage to a clinically manifested disease, the surrounding microenvironment co-evolves into an activated state through continuous and dynamic paracrine communication between all constituent cell types that collectively sustain malignant growth. Hence, from a therapeutic perspective, tumors must be regarded as multi-cellular organs. Mesenchymal cells are highly plastic entities. Normal fibroblasts are described to counteract tumorigenesis by repressing cancer initiation. However, co-evolution of the malignant epithelium and its underlying stroma instigates activation of cancer-associated fibroblasts (CAFs) into a phenotype endorsing most, if not all, hallmarks of cancer progression. Through translational studies using breast cancer patient cohorts, genetically engineered mouse models (including patient derived xenografts), and single-cell RNA sequencing, we delineate a previously unappreciated role for CAFs as determinants of breast cancer prognosis and treatment response through specification of the molecular subtype of breast cancer. Expression of paracrine growth factors mediating malignant cell-CAF crosstalk in breast cancer was found to be associated with a hormone receptor-negative state. Genetic targeting of the signaling networks governing the interactions between tumor cells and CAFs confirmed their functional importance by prompting a delay in tumor growth, impaired extra-cellular matrix deposition and reduced angiogenesis. Importantly, our work holds therapeutic implications, as genetic or therapeutic targeting of CAF subsets resulted in conversion of basal-like/triple-negative breast tumors into a luminal state that conferred sensitivity to endocrine therapy in previously impervious tumors. Additionally, to mechanistically explore the heterogeneity of mesenchymal cells in breast tumors, we have made use of single cell RNA sequencing of isolated CAFs as a guide to divide cells into transcriptionally similar groups. Distinct clusters of different CAF subtypes were identified and found to denote diverse functions in the tumor microenvironment. In conclusion, therapeutic targeting of functional subsets of CAFs may be exploited as a refined strategy to improve patient benefit from established treatments by impinging on the stimulatory crosstalk between CAFs and their surrounding malignant microenvironment. Citation Format: Bocci M, Bartoschek M, Pietras K. Microenvironmental control of breast cancer subtype elicited by paracrine growth factors signaling [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 P4-03-06.
Lower-Extremity Pseudomyogenic Hemangioendothelioma on Bone Scintigraphy and PET/CT
Authors: Simone Krebs, Serena Monti, Natasha Lewis, Alessandro Luciano, Lapo Rastrelli, Lorenzo Mannelli
Journal: Clinical Nuclear Medicine (2017)

An otherwise healthy 33-year-old man presents with new pain involving the right leg. Radiographs of the femur showed scattered lucent lesions. An MRI of the knee demonstrated nonspecific cortical-based lesions. Biopsy confirmed pseudomyogenic hemangioendothelioma. MDP bone scan and F-FDG PET/CT were obtained to evaluate for extent of disease demonstrating disease limited to the bone of the right leg. Interestingly, the FDG and MDP uptake and CT appearance of the disease were not entirely concordant, with some lesions being lytic on CT and associated with FDG and MDP uptake, other lesions being CT silent and either MDP or FDG avid.
Abstract P5-07-06: A novel non-canonical Notch1-IKKα-mTORC2-AKT pathway maintains survival in triple negative breast cancer cells and cancer stem-like cells
Authors: F Hossain, Y Peng, A Pannuti, K Backus, T Golde, B Osborne, L Miele
Journal: Cancer Research (2017)

Abstract Triple negative breast cancer (TNBC) is a heterogeneous group of clinically aggressive breast cancers. TNBC patients have high risk of recurrence and metastasis, and current treatment options remain limited. There is strong evidence for the involvement of Notch signaling in TNBC and in breast cancer stem-like cells (CSCs). Notch1 is highly expressed in Basal-like 1 (BL1) and especially Mesenchymal-Stem-Like (MSL) TNBCs. Expression of Notch1 and its ligand Jagged1 correlate with poor prognosis. Treatment of TNBC with dual mTORC1/2 inhibitors leads to resistance through activation of Notch1. Expression of Notch1 protein correlates with pAKT and nuclear NF-κB in TNBC. Here, we demonstrate that Notch1 promotes cell survival in MDA-MB-231 cells, representative of MSL TNBC, in part by activating NF-κB. Notch activation by Jagged1-expressing stromal cells enhances transcription of the anti-apoptotic gene cIAP-2 (BIRC3), a known NF-κB target. This event is dependent on recruitment to the cIAP-2 promoter of NF-κB subunits, IKKα and Notch1. Short term exposure of MDA-MB-231 cells (MSL, PTEN wild-type), but not MDA-MB-468 cells (BL1, PTEN-null) to recombinant Jagged1 leads to rapid AKT phosphorylation. This is suppressed by dual mTORC1/2 inhibitors, AKT inhibitors and IKKα inhibitors but not Everolimus (mTORC1-selective inhibitor). Rapid AKT phosphorylation downstream of Notch1 requires mTORC2, PI3K and IKKα, and contributes to NF-κB activation. These observations support a model where canonical and non-canonical mechanisms downstream of Notch1 trigger rapid AKT phosphorylation and NF-κB activation in PTEN wild-type TNBC cells. Both arms of this pathway require IKKα. CSCs derived from MDA-MB-231 cells have increased Notch1, pAKT and pIKKα expression. Combined pharmacological inhibition of Notch and AKT or Notch and IKKα completely blocks secondary mammosphere formation. These data and published literature suggest that: 1) IKKα connects the Notch and mTORC2/AKT pathways in some TNBC subtypes; 2) IKKα is also required for nuclear Notch1-mediated NF-kB activation and may be a critical node in the Notch signaling network; 3) A feedback mechanism may exist in some TNBC cells between mTORC2/AKT and Notch1; 4) The non-canonical Notch-IKKα-AKT pathway has a potential therapeutic role in targeting CSCs of selected TNBC subtypes. Citation Format: Hossain F, Peng Y, Pannuti A, Backus K, Golde T, Osborne B, Miele L. A novel non-canonical Notch1-IKKα-mTORC2-AKT pathway maintains survival in triple negative breast cancer cells and cancer stem-like cells [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 P5-07-06.
Variation in lung function as a marker of adherence to oral and inhaled medication in cystic fibrosis
Authors: Helen White, Nicola Shaw, Sarah Denman, Kim Pollard, Sarah Wynne, Daniel Gavin Peckham
Journal: European Respiratory Journal (2017)

The aim of this study was to characterise adherence in an adult population with cystic fibrosis (CF) and to investigate if variation in lung function was a predictor of adherence to treatment. The adherence of patients aged ≥16 years from an adult CF centre was measured by medication possession ratio (MPR) and self-report. Patients were assigned to one of three adherence categories (&lt;50%, 50 to &lt;80%, ≥80%) by their composite score (MPR). Ordinal regression was used to identify predictors of adherence, including coefficient variation measures for forced expiratory volume in 1 s (FEV 1 ), weight and C-reactive protein concentration, measured from 6 months and 12 months before baseline. MPR data for 106 of 249 patients (mean age 29.8±9.2 years) was retrieved, indicating a mean adherence of 63%. The coefficient of variation for FEV 1 was inversely related to adherence and was a univariate predictor of adherence (6 months: OR 0.92, 95% CI 0.87–0.98, p=0.005; 12 months: OR 0.94, 95% CI 0.93–0.99, p=0.03) and remained significant in the final models. The coefficient of variation of weight and C-reactive protein were not predictive of adherence. The coefficient of variation of FEV 1 was identified as an objective predictor of adherence. Further evaluation of this potential marker of adherence is now required.
Abstract P5-11-17: Body image in women with breast cancer using a scalp cooling system to reduce chemotherapy induced alopecia
Authors: T Cigler, SA Melin, P Klein, SA Hurvitz, M Melisko, A Moore, GD Park, E Bageman, ES Ver Hoeve, HS Rugo
Journal: Cancer Research (2017)

Abstract Background: Most women consider hair to be an important part of body image. Alopecia is an emotionally traumatic side effect for breast cancer patients undergoing adjuvant chemotherapy. The DigniCap™ Scalp Cooling System is the first scalp cooling system cleared by the US Food and Drug Administration to reduce the likelihood of chemotherapy induced alopecia. Methods: Quality of Life (QOL) data were collected as part of a prospective clinical trial evaluating the clinical performance of scalp cooling in women with early stage BC receiving adjuvant chemotherapy. The study's primary endpoint was hair loss as evaluated by patient self-assessment. Treatment success was defined as ≤ 50% hair loss. QOL was evaluated by the EORTC-QLQ-BR23 (BR23) administered at baseline, last chemotherapy cycle, and one month later. For BR23, 4 response categories were collapsed to 2 categories (Not at all/A little bit and Quite a bit/Very much) for analysis. QOL was compared between those with success vs. failure of scalp cooling. Results: 101 patients were evaluable for the primary endpoint: Success was seen in 67 (66.3%) pts. QOL at study entry was comparable between pts with scalp cooling success or failure for each item in the BR23 questionnaire. Results reported as percentages of patients in each group who answered either quite a bit or very much to body image-related questions on the BR23 questionnaire are displayed in Table 1. BR23 results (% quite a bit/very much) one month after chemotherapyBR23 ItemsTreatment Success % (95% CI)Treatment Failure % (95% CI)Felt physically less attractive18.5% (9.0%, 27.9%)52.2% (31.8%, 72.6%)Felt less feminine15.4% (6.6%, 24.2%)29.1% (19.2%, 59.1%)Found it difficult to see themselves naked13.8% (5.5%, 22.2%)21.7% (4.9%, 38.6%)Felt dissatisfied with their body12.3% (4.3%, 20.3%)26.1% (8.1%, 44.0%) Conclusions: Women with breast cancer using scalp cooling during chemotherapy who had hair preservation experienced improved quality of life, according to self-assessment of body image, compared to women who had significant hair loss. Citation Format: Cigler T, Melin SA, Klein P, Hurvitz SA, Melisko M, Moore A, Park GD, Bageman E, Ver Hoeve ES, Rugo HS. Body image in women with breast cancer using a scalp cooling system to reduce chemotherapy induced alopecia [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 P5-11-17.
AHNAK2 is a Novel Prognostic Marker and Oncogenic Protein for Clear Cell Renal Cell Carcinoma
Authors: Minglei Wang, Xuefeng Li, Jin Zhang, Qiong Yang, Wenqi Chen, Weilin Jin, Yi-Ran Huang, Ru Yang, Wei-Qiang Gao
Journal: Theranostics (2017)

Integrative database analysis was performed to identify novel candidate oncogene AHNAK2 overexpressed in clear cell renal cell carcinoma (ccRCC).However, the function of AHNAK2 in cancer cells is currently unknown.In this study, we first confirmed the upregulation of AHNAK2 in ccRCC tissues compared with adjacent normal tissues in 15 pairs of samples.Then we analyzed AHNAK2 expression in a large cohort of ccRCC patient samples (n = 355), and found that up-regulation of AHNAK2 was positively correlated with tumor progression and poor survival (p = 0.032).Knockdown of AHNAK2 inhibited cancer cell proliferation, colony formation and migration in vitro and tumorigenic ability in vivo.Meanwhile, knockdown of AHNAK2 impaired the cell oncologic-metabolism by inhibiting lipid synthesis.Moreover, we observed that expression of AHNAK2 was greatly upregulated, at least in part, by hypoxia in cancer cells.By using chromatin immune-precipitation (CHIP) and promoter-luciferase reporter assays, we identified that upregulation of AHNAK2 induced by hypoxia was hypoxia-inducible factor-1α (HIF1α)-dependent.Knockdown of AHNAK2 impaired hypoxia-induced epithelial-mesenchymal transition (EMT) and stem cell-like properties.Considered together, we reveal that AHNAK2 is upregulated in cancer cells and hypoxic upregulation of AHNAK2 can drive tumorigenesis and progression by supporting EMT and cancer cell stemness.Thus, AHNAK2 is a novel prognostic marker and an oncogenic protein for ccRCC.
Abstract P1-03-02: Intratumoral heterogeneity of Ki67 expression in early breast cancers exceeds variability between individual tumours
Authors: CM Focke, T Decker, PJ van Diest
Journal: Cancer Research (2017)

Abstract Background Regional differences in proliferative activity are commonly seen within breast cancers, but little is known on the degree of intratumoral heterogeneity of Ki67 expression. Our aim was to study intratumoral heterogeneity of Ki67 expression in early breast cancers and its association with clinicopathological features like estrogen receptor (ER) status, grade and histological type. Methods The Ki67-labelling index (Ki67-LI) was assessed in hot, cold and intermediate spots of 233 invasive breast cancers by counting a total of 1020 cells, according to a protocol of the International Ki67 in Breast Cancer Working Group. Differences between the spots per tumor were further analyzed for clinicopathological subgroups defined by ER status, grade and histological type. Results All clinicopathological subgroups showed significant differences in Ki67-LI between hot, intermediate and cold spots (p &amp;lt;0.001). The coefficient of variance (CV) between the spots was higher in ER positive than in ER negative cancers (72.6% vs 49.2%, p &amp;lt;0.001), and was highest in grade 3 (96.12%), grade 1 (87.27%) and invasive lobular tumors (83.59%), and lowest in medullary (26.48%) cancers. Nested analysis of variance indicated that in both ER positive and ER negative cancers, variance in Ki67-LI within tumours contributed more to the total variance (56% for ER positive, 60% for ER negative cancers) than the variance between tumors. Conclusion Intratumoral heterogeneity in Ki67-LI is an ubiquitous phenomenon across various pathological subgroups of breast cancer that may impact assessment of Ki67 levels for clinical decision making, and sheds new light on recommended cut-offs. Citation Format: Focke CM, Decker T, van Diest PJ. Intratumoral heterogeneity of Ki67 expression in early breast cancers exceeds variability between individual tumours [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 P1-03-02.
Heterozygosity for the Non-Deletional O2 Allele Does Not Cause Discrepancies in Automated Blood Donor ABO Grouping.
Authors: Mark H. Yazer, Jonathan McGuirt, Åsa Hellberg, Bahram Hosseini-Maaf, Annika Hult, Andrea Cortese-Hassett, Darrell J. Triulzi, Martin L. Olsson
Journal: Blood (2006)
Impact of NK Cell Reconstitution and Recipient HLA-C Typing on Clinical Outcome after Reduced Intensity Cord Blood Transplant: Results of a Prospective Phase II Multicentric Trial on Behalf of Societe Francaise De Greffe De Moelle Osseuse Et Therapie Cellulaire (SFGM-TC) and Eurocord
Authors: Stephanie Nguyen, Laetitia Souchet, Abla Achour, Stéphane Vigouroux, Patrice Chevallier, Sabine Furst, Anne Sirvent, Jacques-Olivier Bay, Gerard Socie, Patrice Ceballos, Anne Huynh, Jérôme Cornillon, Sylvie Francois, Faezeh Legrand, Ibrahim Yakoub-Agha, Gerard Michel, Natacha Maillard, Genevieve Margueritte, Sébastien Maury, Madalina Uzunov, Claude-Eric Bulabois, Mauricette Michallet, Laurence Clément, Charles Dauriac, Karin Bilger, Julie Lejeune, Vivien Beziat, Vanderson Rocha, Bernard Rio, Sylvie Chevret, Vincent Vieillard
Journal: Blood (2015)
Preclinical Studies Using Polyethylenimine (PEI) Nanoparticles Complexed with Eukaryotic Translation Initiation Factor 5A (eIF5A) siRNA and eIF5AK50R Plasmid DNA Demonstrates Significant Anti-Myeloma Activity in Vitro and in Vivo
Authors: John A. Lust, John E. Thompson, Catherine A. Taylor, Bin Ye, Zhongda Liu, Zhong Sun, Richard S. Dondero, Laurie L. Moon-Tasson, Michael P. Kline, Kathleen A. Donovan
Journal: Blood (2008)
Faecal microbiota transplantation in clinical practice
Authors: E M Terveer, Y H van Beurden, A Goorhuis, C J J Mulder, E J Kuijper, J J Keller
Journal: Gut (2017)

Dear Sir,

We would like to add some remarks to the report of a consensus meeting about faecal microbiota transplantation (FMT) by Cammarota et al. 1

Already, donor faeces banks exist at an institutional or national level in Germany, UK and The Netherlands, to support treatment of patients with recurrent Clostridium difficile infection (CDI).2 Unfortunately, these centres were not consulted for advice, and it is felt that some conclusions of the report need clarification and adjustments.

First, the statement about expert centres is inaccurate. The critical steps for safe and effective FMT are (1) patient selection, (2) donor (stool) selection and screening, and (3) biobanking of faeces suspensions. We agree that donor screening should be performed …
A phase I study of buparlisib (BKM120) with bevacizumab (BEV) in patients (pts) with metastatic renal cell carcinoma (mRCC) progressing on prior vascular endothelial growth factor (VEGF) therapies.
Authors: Rana R. McKay, Lillian Werner, Lauren Christine Harshman, Joaquim Bellmunt, Christopher Sweeney, Jonathan E. Rosenberg, Eliezer VanAllen, Meghara K. Walsh, Ulka N. Vaishampayan, David F. McDermott, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2015)

4559 Background: BKM120 is a pan-PI3K inhibitor with demonstrated activity in advanced solid tumors. The primary aim of this study was to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of BKM120 + BEV. Secondary objectives included safety, efficacy, and biomarker discovery. Methods: This was a 3+3 dose escalation study of BKM120 (60-100 mg/day (d)) + BEV (10 mg/kg every 2 weeks). After the MTD was defined, 14 pts were accrued to the expansion cohort. Results: A total of 32 pts were accrued (5 treated at 60 mg/d, 19 at 80 mg/d (2 remain on therapy), 6 at 100 mg/d, and 2 never received therapy). The majority had clear cell histology (88%) and 50% had ≥2 prior lines of systemic therapy. The MTD of BKM120 was 80 mg/d. With the exception of 1 case of cognitive disturbance deemed related to both agents, all DLTs (Table 1) were attributed to BKM120. 28 pts discontinued therapy: 16 due to progression, 7 dueto toxicity, 1 due to death, and 4 due to other reasons. Toxicity leading to therapy discontinuation included rash/pruritis, transaminitis, elevated lipase/amylase, suicidal ideation, and cognitive disturbances. Of the 30 pts who received at least 1 dose, 13% had a partial response (PR) (95% CI 4%, 31%), 50% had stable disease (SD), and 20% had progressive disease (PD). Of the 19 pts treated at the MTD, 11% had a PR (95% CI 1%, 33%), 53% had SD, and 16% had PD. The median time-to-treatment failure (TTF), progression-free survival (heavy censoring) and overall survival were 4 (95% CI 2, 9), 9 (95% CI 2, 9), and 18 (95% CI 4, not reached) months (mos) for the total cohort and 4 (95% CI 2, 9), 6 (95% CI 2, 9), and 13 (95% CI 5, not reached) mos for pts treated at the MTD, respectively. Of the 9 pts evaluated, 2 had activating PI3K mutations. One achieved a PR (TTF 13 mos) and the other achieved SD with 16% tumor shrinkage (TTF 9 mos). Conclusions: BKM120 at 80 mg/d + BEV was a tolerable regimen with preliminary activity in VEGF-refractory mRCC. Clinical trial information: NCT01283048.Summary of DLTs. Case DLT Grade BKM Dose 11 Anxiety 3 100 mg Depression 3 Suicidal ideation 3 12 Anorexia 3 100 mg Weight loss 3 15 Cognitive disturbance 2* 80 mg *≥1 CTCAE grade level increase defined as DLT.