tbuckley/cabot-search huggingface dataset:
Treatments (tx) after progression to first-line FOLFOXIRI plus bevacizumab (bev) in metastatic colorectal cancer (mCRC) patients (pts): A pooled analysis of TRIBE and MOMA studies by GONO group.
Authors: Daniele Rossini, Roberto Moretto, Chiara Cremolini, Vittorina Zagonel, Giuseppe Tonini, Vincenzo Ricci, Giuseppe Aprile, Sara Lonardi, Gianluca Tomasello, Emanuela Dell'Aquila, Giacomo Allegrini, Francesca Bergamo, Marialaura Mancini, Carlotta Antoniotti, Monica Ronzoni, Alberto Zaniboni, Federica Marmorino, Sara Bustreo, Elena Mori, Alfredo Falcone
Journal: Journal of Clinical Oncology (2017)

3542 Background: FOLFOXIRI plus bev is regarded by international guidelines as a valuable option in the first-line tx of mCRC pts. One of the major concerns for the adoption of this regimen is the potential limitation of subsequent therapeutic options. The aim of the present analysis was to focus on treatments received after progression in TRIBE (NCT00719797) and MOMA (NCTNCT02271464) studies. Methods: We collected data of tx received after progression and their outcome in terms of 2 nd PFS (time from 2nd line tx start to disease progression or death) and OS II (time from 2nd line tx start to death). For pts in which the same drugs used in first-line were totally or partially reintroduced, the chemotherapy-free interval (CFI, time from the last administration of irinotecan or oxaliplatin during first-line to disease progression) was calculated. Results: Out of 482 pts treated with upfront FOLFOXIRI plus bev, 429 progressed. 303 (70.6%) pts received a 2nd line tx: 93 FOLFOXIRI +/- bev (Group A), 119 FOLFOX/XELOX or FOLFIRI +/- bev (Group B) and 91 other tx (Group C), including an anti-EGFR moAb in 60 cases. No difference was observed among the three groups in terms of 2 nd PFS (median 2 nd PFS Group A: 5.6 vs Group B: 4.4 vs Group C: 3.9 mos; p = 0.60) or OS II (median OS II Group A: 14.9 vs Group B: 13.8 vs Group C: 11.7 mos; p = 0.49). In the subgroup of pts with a CFI &lt; 6 mos, Group A (n = 52) reported longer 2 nd PFS compared to both Group B (n = 58) (median 2 nd PFS 5.3 vs 3.0 mos; HR: 0.61,95%CI 0.41-0.89; p = 0.009) and Group C (n = 58) (5.3 vs 3.2 mos; HR: 0.71, 95%CI 0.48-1.05; p = 0.07). Consistent results were achieved in OS II (Group A vs Group B; median OS 13.6 vs 10.8 mos; HR: 0.65, 95%CI 0.42-1.00; p = 0.053; Group A vs Group C 13.6 vs 8.9 mos; HR: 0.60, 95%CI 0.39-0.93; p = 0.002). In the subgroup of pts with a CFI ≥ 6 mos, no significant difference was shown between Group A (n = 41) and Group B (n = 61) or C (n = 33). Conclusions: Tx after progression to first-line FOLFOXIRI plus bev are feasible and show expected efficacy results. The reintroduction of the triplet plus bev seems more effective than doublets plus bev or other tx when a more aggressive disease biology is suggested (CFI &lt; 6 mos).
Dietary Fat Intake and Lung Cancer Risk: A Pooled Analysis
Authors: Jae Jeong Yang, Danxia Yu, Yumie Takata, Stephanie A. Smith-Warner, William Blot, Emily White, Kim Robien, Yikyung Park, Yong-Bing Xiang, Rashmi Sinha, DeAnn Lazovich, Meir Stampfer, Rosario Tumino, Dagfinn Aune, Kim Overvad, Linda Liao, Xuehong Zhang, Yu-Tang Gao, Mattias Johansson, Walter Willett, Wei Zheng, Xiao-Ou Shu
Journal: Journal of Clinical Oncology (2017)

Purpose Dietary fat may play a role in lung carcinogenesis. Findings from epidemiologic studies, however, remain inconsistent. In this pooled analysis of 10 prospective cohort studies from the United States, Europe, and Asia, we evaluated the associations of total and specific types of dietary fat with lung cancer risk. Methods Cox regression was used to estimate hazard ratios (HRs) and 95% CIs in each cohort. Study-specific risk estimates were pooled by random- or fixed-effects meta-analysis. The first 2 years of follow-up were excluded to address potential influence of preclinical dietary changes. Results Among 1,445,850 participants, 18,822 incident cases were identified (mean follow-up, 9.4 years). High intakes of total and saturated fat were associated with an increased risk of lung cancer (for highest v lowest quintile: HR, 1.07 and 1.14, respectively; 95% CI, 1.00 to 1.15 and 1.07 to 1.22, respectively; P for trend for both &lt; .001). The positive association of saturated fat was more evident among current smokers (HR, 1.23; 95% CI, 1.13 to 1.35; P for trend &lt; .001) than former/never smokers ( P for interaction = .004), and for squamous cell and small cell carcinoma (HR, 1.61 and 1.40, respectively; 95% CI, 1.38 to 1.88 and 1.17 to 1.67, respectively; P for trend for both &lt; .001) than other histologic types ( P for heterogeneity &lt; .001). In contrast, a high intake of polyunsaturated fat was associated with a decreased risk of lung cancer (HR, 0.92; 95% CI, 0.87 to 0.98 for highest v lowest quintile; P for trend = .02). A 5% energy substitution of saturated fat with polyunsaturated fat was associated with a 16% to 17% lower risk of small cell and squamous cell carcinoma. No associations were found for monounsaturated fat. Conclusion Findings from this large, international cohort consortium suggest that modifying dietary fat intake (ie, replacing saturated fat with polyunsaturated fat) may reduce lung cancer risk, particularly among smokers and for squamous cell and small cell carcinoma.
Possible Device Malfunction in a Dual-Chamber Pacemaker
Authors: Jared W. Hornberger, Emilio Fentanes, Gregg G. Gerasimon
Journal: JAMA Internal Medicine (2017)

A man in his 60s with a medical history of hypertension and pacemaker implantation several years prior for symptomatic sinus node dysfunction was admitted to the hospital for evaluation of abdominal pain.
MEG2 is regulated by miR-181a-5p and functions as a tumour suppressor gene to suppress the proliferation and migration of gastric cancer cells
Authors: Zhijian Liu, Feng Sun, Yeting Hong, Yanqing Liu, Min Fen, Kai Yin, Xiaolong Ge, Feng Wang, Xi Chen, Wenxian Guan
Journal: Molecular Cancer (2017)

Protein-tyrosine phosphatase MEG2 (MEG2) is a classic tyrosine-specific protein tyrosine phosphatase (PTP). It has been reported that MEG2 participates in the carcinogenesis of the breast and liver. However, functions of MEG2 in gastric cancer remain poorly understood. We examined the expression of MEG2 protein by western blotting and that of miR-181a-5p by qRT-PCR. We used bioinformatic analyses to search for miRNAs that potentially target MEG2. We performed a luciferase reporter assay to investigate the interaction between miR-181a-5p and MEG2. In addition, we assessed the effects of MEG2 and miR-181a-5p on gastric cancer cells in vitro and in vivo. We found that MEG2 is downregulated in human gastric cancer and that miR-181a-5p is predicted to be a potential regulator of MEG2. We also observed that expression of MEG2 is reversely correlated with that of miR-181a-5p in gastric cancer. Moreover, we observed that MEG2 regulation by miR-181a-5p significantly suppresses the proliferation and migration of gastric cancer cells in vitro and decelerates tumour growth in vivo. Our results revealed that MEG2 is a tumour suppressor gene and negatively regulated by miR-181a-5p in gastric cancer.
Prognostic role of chromogranin A expression for docetaxel response in hormone-refractory metastatic prostate cancer
Authors: A. Gernone, S. Trabucco, G. Troccoli, V. Pagliarulo, A. Pagliarulo
Journal: Journal of Clinical Oncology (2007)

15528 Background: The neuroendocrine (NE) cells in prostate cancer are indistinguishable from non-NE cancer cells morphologically and are usually detected by immunohistochemical study for NE markers. We analyzed the expression of Chromogranin A (Chr A) in malignant prostate tissue as prognostic factor for docetaxel response in metastatic HRPC. Methods: From January 2003 to December 2006, 40 patients with metastatic HRPC received a median of 12 cycles (range 2–18) of Docetaxel 75 mg/mq every 21 days and 5 mg of prednisone twice daily as initial therapy. Tissue blocks from primary prostate cancer tissues were obtained and immunostaining for Chr A was performed. The median age was 70 years (range 46–82); median baseline PSA: 310 ng/ml (range 0.15–700); median ECOG Performance Status: 1 (range 0- 2). PSA level was measured every 4 weeks and the treatment was considered effective if a rate of PSA-decline &gt; 50% from baseline was found. TTP was the preliminary end point. Results: Response to Docetaxel was assessed at every 3 cycles of treatment. The Chr A expression was found in 19/40 patients with Gleason = 7, PSA &lt; 20, bone and soft tissue metastasis; 10 of them showed PR (decrease in PSA &lt; 50%), 4 SD and TTP was 9.2 months. Moreover they received second line chemotherapy without significant efficacy. 5/19 patients with Chr A expression showed PD, the PSA level was not correlated with clinical outcome, TTP was 5 months and were chemoresistant to different line treatment. Besides, Chr A was not detected in 21/40 patients with Gleason = 7, PSA &gt; 20 and bone metastasis; 10 of them showed CR (PSA normalized) and 11 PR, TTP was 20 months. Conclusions: NE differentiation do not constituite a different histopathological category of prostate cancer but the NE phenotype can be correlated with poorly differentiated adenocarcinoma. NE differentiation can be considered a factor that influences prognosis and treatment in advanced prostate cancer; cases with Chr A expression did not benefit from Docetaxel and had poor prognosis. These preliminary data indicate that initial therapeutic approach should be different according to Chr A expression. No significant financial relationships to disclose.
Neutrophil extracellular traps induced by cigarette smoke activate plasmacytoid dendritic cells
Authors: Shi-Lin Qiu, Hui Zhang, Qi-ya Tang, Jing Bai, Zhi-Yi He, Jian-Quan Zhang, Mei-Hua Li, Jing-Min Deng, Guang-Nan Liu, Xiao-Ning Zhong
Journal: Thorax (2017)

<h3>Background</h3> Neutrophil extracellular traps (NETs) represent a distinct strategy by which neutrophils trap, confine and eliminate invading microorganisms. Emerging evidence suggests that NETs exert a deleterious effect to the host in the absence of microbial stimuli. However, the role of NETs in smoking-related lung diseases remains to be elucidated. <h3>Objectives</h3> To evaluate the formation of NETs in the context of chronic inflammation induced by cigarette smoking and explore its potential role in an experimental mouse model of emphysema. <h3>Methods</h3> The formation and degradation of NETs in cigarette smoke exposed mice was assessed with a fluorescence microscope. The potential influences of NETs on plasmacytoiddendritic cells were also investigated. <h3>Results</h3> NETs were more prone to formation by polymorphonuclearneutrophils but defective in degradation in cigarette smoke exposed mice. Cigarette smoke extract (CSE) served as an important facilitator that triggered neutrophils to undergo NETosis in vitro. Furthermore, CSE-induced NETs were capable of driving plasmacytoiddendritic cell maturation and activation, thereby initiating a T-cell-mediated immune response. <h3>Conclusions</h3> NETs may represent a critical connection between innate and adaptive immune responses under conditions of chronic inflammation induced by cigarette smoke exposure.
Physical and Psychological Factors Influencing Fatigue and Quality of Life in Multiple Myeloma Survivors: Preliminary Results from the Mascot Lifestyle Study
Authors: Malgorzata Heinrich, Joanne Land, Orla McCourt, Stephanie Philpott, Bruce Paton, Rebecca J Beeken, Lee Smith, Dunnya De-Silva, Ali Rismani, Shirley D'Sa, Anastasia Chew, Atul Mehta, Abigail Fisher, Allan Hackshaw, Kwee L Yong
Journal: Blood (2016)
Abstract 341: Transplantation of Cardiac Tissue Sheets Including Defined Cardiovascular Cell Populations Differentiated from Human-Induced Pluripotent Stem Cells Ameliorates Cardiac Dysfunction After Subacute Myocardial Infarction
Authors: Hidetoshi Masumoto, Tadashi Ikeda, Tatsuya Shimizu, Teruo Okano, Ryuzo Sakata, Jun K Yamashita
Journal: Circulation Research (2012)

BACKGROUNDS: To realize cardiac regeneration with human induced pluripotent stem cells (hiPSCs), efficient differentiation from hiPSCs to defined cardiac cell populations (cardiomyocytes [CMs]/ endothelial cells [ECs]/ vascular mural cells [MCs]), and transplantation technique for fair engraftment are required. Recently, we reported that mouse ES cell-derived cardiac tissue sheet transplantation to rat myocardial infarction (MI) model ameliorated cardiac function after MI (Stem Cells, in press). Here we tried to extend this technique to hiPSCs. METHODS &amp; RESULTS: We have reported an efficient cardiomyocyte differentiation protocol based on a monolayer culture (PLoS One, 2011), in which cardiac troponin-T (cTnT)-positive CMs robustly appeared with 50-80% efficiency. In this study, we further modified the protocol to induce vascular cells (ECs/MCs) together with CMs by vascular endothelial cell growth factor supplementation, resulted in proportional differentiation of cTnT+-CMs (62.7±11.7% of total cells), VE-cadherin+-ECs (7.8±4.9%) and PDGFRb+-MCs (18.2±11.0%) at differentiation day 15 (n=12). Then, these cells were transferred onto temperature-responsive culture dishes (UpCell dishes; CellSeed, Tokyo, Japan) to form cardiac tissue sheets including defined cardiac populations. After 4 days of culture, we successfully collected self-pulsating cardiac tissue sheets with 7.0×10 5 ±2.3 (n=12) of cells consisted of CMs (46.9±15.9% of total cells), ECs (4.1±3.7%), and MCs (22.5±15.7%). Three-layered hiPSC-derived cardiac sheets were transplanted to a MI model of athymic rat heart one week after MI. In transplantation group, echocardiogram showed a significant improvement of systolic function of left ventricle (fractional shortening: 22.6±5.0 vs 36.5±8.0%, p&lt;0.001, n=20) and a decrease in akinetic length (20.8±9.7 vs 2.5±7.7%, p&lt;0.001, n=20) (pre-treatment vs 4weeks after transplantation). We also succeeded in generation of larger sheets (1.6 inch diameter) with the same method. CONCLUTIONS: Transplantation of hiPSC-derived cardiac tissue sheets significantly ameliorates cardiac dysfunction after MI. Thus, we developed a valuable technological basis for hiPSC-based cardiac cell therapy.
Phase I dose-finding and pharmacokinetic study of IV vinflunine in combination with methotrexate in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) previously treated with platinum-based chemotherapy.
Authors: Audrey Mailliez, Frederic Rolland, Jean Marc Tourani, Cedrik Lafond, Didier Cupissol, Nicolas Isambert
Journal: Journal of Clinical Oncology (2015)

e17049 Background: There is a clinical need to improve outcomes of patienys (pts) with R/M SCCHN who failed platinum-based therapy. Methotrexate (MTX) remains a standard option but its efficacy remains unsatisfactory. This Phase I study aimed to determine the recommended dose (RD) and pharmacokinetics of the combination Vinflunine (VFL) plus MTX. Methods: This trial used 3+3 dose-escalation design. Dose limiting toxicity (DLT) was defined as grade (G) 4 neutropenia lasting ≥ 7 days, G4 thrombocytopenia or G3 with significant bleeding or requiring platelets transfusion; febrile neutropenia, and G3-4 non-haematological toxicity; treatment delay > 2 weeks due to unresolved toxicity after cycle 1. VFL dose was fixed at 280 mg/m² given on day 1 every 3 weeks. MTX was tested on a range of 20 to 40 mg/m² given on D1 and D8 of 3-week cycle. Because of the poor tolerance of the combination at doses of MTX greater than to 20 mg/m², the protocol was amended, restricting the population to fit pts with normal albumin level, and without significant weight loss or recurrent pulmonary or upper airways infections in the previous 3 months before study entry. A total of 34 pts were enrolled, 33 treated and 25 evaluable for RD determination. Results: Before amendment, the RD was VFL 280 mg/m² D1 + MTX 20 mg/m² D1, D8. After amendment, RD was VFL 280 mg/m² D1 + MTX 30 mg/m² D1, D8. DLTs observed were constipation, febrile neutropenia, neutropenic infection and ileus. At the RD, after amendment, the main toxicities were G3-4 neutropenia (76.9%), constipation (57.1%, no G3-4 cases), stomatitis (14.3%, no G3-4 cases), nausea, (42.9%, no G3-4 cases), asthenia (42.9%; G3-4 14.3%), G3-4 neutropenic sepsis (14.3%). Objective responses were reported in 5 pts (21.7%, 5/23) and stable disease in 7 pts (30.4%) achieving a disease control (CR+PR+SD) in 12 pts (52.2%). The PK analysis showed no effect of MTX on the PK of VFL and no effect of VFL on the PK of MTX when both drugs were given in combination. Conclusions: VFL plus MTX showed an acceptable safety profile, at the recommended dose in fit pts and an encouraging antitumour activity.
Proposed Classification of the Murine Leukemia-Sarcoma Viruses
Journal: JNCI Journal of the National Cancer Institute (1972)

Proposed Classification of the Murine Leukemia-Sarcoma Viruses Get access Richard Siegler, M.D. Richard Siegler, M.D. Children' s Cancer Research Foundation Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 49, Issue 3, September 1972, Pages 923–924, https://doi.org/10.1093/jnci/49.3.923 Published: 01 September 1972
Update: Interim Guidance for Health Care Providers Caring for Pregnant Women with Possible Zika Virus Exposure — United States (Including U.S. Territories), July 2017
Authors: Titilope Oduyebo, Kara D. Polen, Henry T. Walke, Sarah Reagan-Steiner, Eva Lathrop, Ingrid B. Rabe, Wendi L. Kuhnert-Tallman, Stacey W. Martin, Allison T. Walker, Christopher J. Gregory, Edwin W. Ades, Darin S. Carroll, Maria Rivera, Janice Perez-Padilla, Carolyn Gould, Jeffrey B. Nemhauser, C. Ben Beard, Jennifer L. Harcourt, Laura Viens, Michael Johansson, Sascha R. Ellington, Emily Petersen, Laura A. Smith, Jessica Reichard, Jorge Munoz-Jordan, Michael J. Beach, Dale A. Rose, Ezra Barzilay, Michelle Noonan-Smith, Denise J. Jamieson, Sherif R. Zaki, Lyle R. Petersen, Margaret A. Honein, Dana Meaney-Delman
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

† Symptoms of Zika virus disease include acute onset of fever, maculopapular rash, arthralgia, or conjunctivitis.§ Persons with ongoing possible Zika virus exposure include those who reside in or frequently travel (e.g., daily or weekly) to an area with risk for Zika virus transmission.¶ For the purposes of this guidance, recent possible Zika virus exposure or Zika virus/flavivirus infection is defined as a possible exposure or infection during the current pregnancy or periconceptional period (i.e., 8 weeks before conception or 6 weeks before the last menstrual period).
Abstract 2664: Eradication of neuroblastoma by suppressing the expression of a single long noncoding RNA
Authors: Andrew E. Tee, Pei Y. Liu, Giorgio Milazzo, Jo Vandesompele, Glenn M. Marshall, Giovanni Perini, Pieter Mestdagh, Marcel Dinger, Tao Liu
Journal: Cancer Research (2016)

Abstract Neuroblastoma is the most common solid tumour in early childhood, and accounts for approximately 15% of all childhood cancer death. N-Myc gene amplification occurs in one quarter to one third of human neuroblastoma tissues, and the majority of patient with neuroblastoma due to N-Myc gene amplification die of the disease. We performed RNA sequencing experiments, and identified 5 transcripts, including RP1X, which were considerably differentially expressed between N-Myc gene amplified and non-amplified human neuroblastoma cell lines. Affymetrix microarray studies revealed that DEPD was one of the few genes considerably down-regulated in neuroblastoma cells after RP1X depletion. Chromatin immunoprecipitation assays showed that knocking-down RP1X expression reduced histone H3 lysine 4 trimethylation, a marker for active gene transcription, at the DEPD gene promoter. Depletion of RP1X or DEPD significantly reduced ERK protein phosphorylation, N-Myc protein phosphorylation at Serine 62, N-Myc protein stabilization, neuroblastoma cell proliferation and survival. Clonogenic assays showed that knocking-down RP1X with doxycycline completely abolished colony formation capacity of neuroblastoma cells stably transfected with doxycycline-inducible RP1X shRNA. Importantly, treatment with doxycycline in mice xenografted with neuroblastoma cells stably transfected with doxycycline-inducible RP1X shRNA, led to tumour eradication. In human neuroblastoma tissues from 600 neuroblastoma patients, high levels of RP1X gene expression correlated with DEPD gene expression and poor patient prognosis. In conclusion, this study identifies the novel long noncoding RNA RP1X as an important regulator of N-Myc protein stability and neuroblastoma tumourigenesis. Citation Format: Andrew E. Tee, Pei Y. Liu, Giorgio Milazzo, Jo Vandesompele, Glenn M. Marshall, Giovanni Perini, Pieter Mestdagh, Marcel Dinger, Tao Liu. Eradication of neuroblastoma by suppressing the expression of a single long noncoding RNA. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2664.
Multimodal Regulation of Cardiac Myocyte Proliferation
Authors: Xuejun Yuan, Thomas Braun
Journal: Circulation Research (2017)

Efficient cardiac regeneration is closely associated with the ability of cardiac myocytes to proliferate. Fetal or neonatal mouse hearts containing proliferating cardiac myocytes regenerate even extensive injuries, whereas adult hearts containing mostly post-mitotic cardiac myocytes have lost this ability. The same correlation is seen in some homoiotherm species such as teleost fish and urodelian amphibians leading to the hypothesis that cardiac myocyte proliferation is a major driver of heart regeneration. Although cardiomyocyte proliferation might not be the only prerequisite to restore full organ function after cardiac damage, induction of cardiac myocyte proliferation is an attractive therapeutic option to cure the injured heart and prevent heart failure. To (re)initiate cardiac myocyte proliferation in adult mammalian hearts, a thorough understanding of the molecular circuitry governing cardiac myocyte cell cycle regulation is required. Here, we review the current knowledge in the field focusing on the withdrawal of cardiac myocytes from the cell cycle during the transition from neonatal to adult stages.