tbuckley/cabot-search huggingface dataset:
MALAT1: a druggable long non-coding RNA for targeted anti-cancer approaches
Authors: Nicola Amodio, Lavinia Raimondi, Giada Juli, Maria Angelica Stamato, Daniele Caracciolo, Pierosandro Tagliaferri, Pierfrancesco Tassone
Journal: Journal of Hematology & Oncology (2018)

The deeper understanding of non-coding RNAs has recently changed the dogma of molecular biology assuming protein-coding genes as unique functional biological effectors, while non-coding genes as junk material of doubtful significance. In the last decade, an exciting boom of experimental research has brought to light the pivotal biological functions of long non-coding RNAs (lncRNAs), representing more than the half of the whole non-coding transcriptome, along with their dysregulation in many diseases, including cancer. In this review, we summarize the emerging insights on lncRNA expression and functional role in cancer, focusing on the evolutionary conserved and abundantly expressed metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) that currently represents the best characterized lncRNA. Altogether, literature data indicate aberrant expression and dysregulated activity of MALAT1 in human malignancies and envision MALAT1 targeting as a novel treatment strategy against cancer.
Comparative Genomics Reveals a Burst of Homoplasy-Free Numt Insertions
Authors: Bin Liang, Ning Wang, Nan Li, Rebecca T Kimball, Edward L Braun
Journal: Molecular Biology and Evolution (2018)

Mitochondrial DNA sequences are frequently transferred into the nuclear genome, giving rise to numts (nuclear mitochondrial DNA segments). In the absence of whole genomes, avian numts have been suggested to be rare and relatively short. We examined 64 bird genomes to test hypotheses regarding numt frequency, distribution among taxa, and likelihood of homoplasy. We discovered 100-fold variation in numt number across species. Two songbirds, Geospiza fortis (Darwin's finch) and Zonotrichia albicollis (white-throated sparrow) had the largest number of numts. Ancestral state reconstruction of 957 numt insertions in these two species and their close relatives indicated a remarkable acceleration of numt insertion in the ancestor of Geospiza and Zonotrichia followed by slower, continued accumulation in each lineage. These numts appear to result primarily from de novo insertion with the duplication of existing numts representing a secondary pathway. Insertion events were essentially homoplasy-free and numts appear to represent perfect rare genomic changes.
Predictors of pediatric and adult fibrosarcoma survival: Analyses of the Surveillance, Epidemiology, and End Results (SEER) program, 1973-2008.
Authors: Simona Ognjanovic, Yunhua Fan, Miodrag Ognjanovic, Stephen Skapek, Douglas S. Hawkins
Journal: Journal of Clinical Oncology (2012)

1576 Background: Fibrosarcoma (FS) is the second most common group of soft tissue sarcomas in children, however, most FS are diagnosed in adults. The goal of this study was to compare clinical features and outcomes of children and adults diagnosed with FS and identify predictors of survival. Methods: We have analyzed data from 569 children (≤ 19 years) and 5,508 adults (&gt;19 years) diagnosed between 1973 and 2008 with FS (ICCC category IXb) available in the SEER database. Survival estimates were determined using survival time with end point death from any cause. Results: Comparison of two diagnostic periods, 1973-1989 vs. 1990-2008 showed that 5-year survival rates have improved in adults (48.4% vs 60.9%, P&lt;0.0001), but not in children (72.3% vs. 73.9%, P=0.16). Children with FS had significantly better outcome compared to adults (5-year survival rates were 73.4% ± 2%, and 56.7% ± 0.7%, respectively, P&lt;0.0001). Sites with survival rates higher than the median 5-year survival were grouped as favorable (extremities, head and neck, and genitourinary site); trunk, abdomen, and other sites were grouped as unfavorable. Cox proportional hazard regression model identified diagnosis in childhood, fibromyxosarcoma histologic subtype (ICD-O3 code 8811/3), favorable site, and localized stage as positive predictors of survival. Compared to fibromyxosarcoma, other histologic types had hazard ratio (HR) of 11.6 (95% CI= 1.6-83.2, P=0.01) in children, and HR of 1.8 (95%CI=1.5-2.1, P&lt;0.0001) in adults. Diagnosis at unfavorable site was associated with HR=1.9 (95%CI=1.4-2.6) in children and HR=1.4 (95%CI=1.3-1.5) in adults. Compared to localized, distant disease had HR=4.2 in children and HR=5.1 in adults, both highly significant (P&lt;0.0001). Conclusions: Adults diagnosed with FS had worse survival than children. Predictors of good outcome, including histiologic subtype, primary site, and stage, were valid in both children and adults.
Proinflammatory CX3CR1+CD59+Tumor Necrosis Factor–Like Molecule 1A+Interleukin‐23+ Monocytes Are Expanded in Patients With Ankylosing Spondylitis and Modulate Innate Lymphoid Cell 3 Immune Functions
Authors: Francesco Ciccia, Giuliana Guggino, Michael Zeng, Ranjeny Thomas, Vidya Ranganathan, Arifur Rahman, Riccardo Alessandro, Aroldo Rizzo, Laura Saieva, Federica Macaluso, Sergio Peralta, Diana Di Liberto, Francesco Dieli, Paola Cipriani, Roberto Giacomelli, Dominique Baeten, Nigil Haroon
Journal: Arthritis & Rheumatology (2018)

Gut-derived innate lymphoid cell 3 (ILC3) has been shown to participate in the pathogenesis of ankylosing spondylitis (AS). CX3 CR1+ mononuclear phagocytes (MNPs) have been demonstrated to modulate ILC3 function in the gut. This study was undertaken to investigate the role of proinflammatory CX3 CR1+CD59+ MNPs in modulating ILC3 function in AS patients.MNP subsets in the blood of AS patients and controls were analyzed by flow cytometry. The presence of CX3 CR1+CD59+ cells in tissue was confirmed by confocal microscopy. Expression of the proinflammatory chemokines CX3 CL1 and CCL2 and decoy receptor 6 (DcR-6) was analyzed. Peripheral CX3 CR1+CD59+ cells were cocultured with ILC3, and changes in their frequency were evaluated by flow cytometry. Transcriptome analysis of circulating CX3 CR1+ monocytes was also performed.DcR-6 deficiency and CCL2 overexpression were observed in inflamed tissues from AS patients. In the gut, the proinflammatory CX3 CR1+CD59+ MNP population was expanded, correlated with the presence of bacteria, and produced high levels of tumor necrosis factor-like molecule 1A (TL1A) and interleukin-23 (IL-23). MNPs positive for CD11b, CD11c, and major histocompatibility complex class II, predominantly expressing CX3 CR1, were also expanded in the small intestines of treatment-naive SKG relative to BALB/c mice. The frequency of gut-derived CX3 CR1+CD59+CCR9+TL1A+IL-23+ MNPs was significantly higher in the peripheral blood and synovial fluid of AS patients than controls. CCR9+CX3 CR1+CD59+ monocytes were also expanded in AS synovial and bone marrow samples. Transcriptome analysis of isolated CX3 CR1+CD59+ monocytes demonstrated a specific proinflammatory profile in AS. Isolated proinflammatory CX3 CR1+CD59+ MNPs from AS patients induced the expansion and activation of ILC3.Proinflammatory CX3 CR1+CD59+TL1A+IL-23+ MNPs are expanded in AS patients and display a specific proinflammatory transcriptome profile. Given the ability of these cells to support ILC3 expansion, they may promote a sustained proinflammatory status in AS.
Proptosis and Double Vision in a Child
Authors: Amanda J. Lu, Jenna M. Kim, Adeniyi Fisayo
Journal: JAMA Neurology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Systematic review and individual patient data based meta-analysis of palonosetron trials for chemotherapy induced nausea and vomiting.
Authors: Yuki Okada, Koji Oba, Naoto Furukawa, Yoshito Komatsu, Yoshimasa Kosaka, Kenji Okita, Satoshi Yuki, Luigi Celio, Matti S. Aapro
Journal: Journal of Clinical Oncology (2017)

e21688 Background: Several clinical trials have evaluated the need for corticosteroid-containing antiemetic regimens on the days after the first 24 hours to control delayed chemotherapy-induced nausea and vomiting (CINV) during moderate emetogenic chemotherapy (MEC) or anthracycline and/or cyclophosphamide (AC)-containing chemotherapy. Methods:We conducted systematic review using research databases and trial registries for any randomized controlled trials reporting CINV outcomes for a single 1-day-dexamethasone (D1 group) containing antiemetic regimen in chemotherapy-naive adult patients scheduled to receive a MEC or AC-containing chemotherapy, compared with additional dexamethasone on days 2 and 3 (D3 group). We also gathered the individual patient data (IPD) from each study investigator. The primary endpoint was complete response (CR: no vomiting and no rescue antiemetics) in the 5-day study period. Secondary efficacy end points were CR rates in 0–24 h and CR rates in 24–120 h; complete control in the overall, acute, delayed periods. An IPD meta-analysis was conducted to quantify the pooled risk differences between D1 group and D3 group and its interaction with patient characteristics using a fixed effect model. Results: Of 887 articles screened, 5 eligible studies were identified comprising 1194 patients, all enrolled in the meta-analysis. Overall, D1 group was not significantly inferior to D3 group in CR rate as well as CC rate [pooled risk difference in CR rate -1.5%, 95% confidence interval (CI) -7.1–4.0%; in delayed CR rate -2.4%, 95% CI -7.7–2.9%]. There was no significant interaction between dexamethasone regimen and patient characteristics (sex, age category ( &lt; 60 or 60 years), and alcohol consumption). Conclusions: These results strongly suggest that the dexamethasone-sparing regimen is not associated with a significant loss in overall antiemetic control in an adult patient undergoing MEC or AC-containing chemotherapy, irrespective of patient baseline characteristics. These data contribute to simplify antiemetic regimens and spare many patients from the potential side-effects of multiple-day corticosteroids.
Predictors for survival in patients with pure mucinous breast carcinoma: A retrospective analysis of 8048 cases.
Authors: Shuning Ding, Li Zhu, Jiayi Wu
Journal: Journal of Clinical Oncology (2018)

e12547 Background: Pure mucinous breast carcinoma (PMBC) is a rare pathological subtype of breast cancer. The prognostic factors have not been clearly defined in this uncommon subtype. This study aims to analyze the prognostic markers in patients with PMBC. Methods: Utilizing the Surveillance, Epidemiology and End Results (SEER) database, a retrospective analysis of PMBC cases reported between 2004 and 2014 was conducted. Univariate and Multivariate analyses were used to evaluate the indicators for prognosis. Results: Of the 8048 patients reported, the median age was 68. About two thirds of patients had T1 tumors, and 90.5% of the patients without lymph nodes involvment. 98.2% patients had ER/PR expression. Mulitivariate analysis revealed that age, race, tumor size, lymph nodes status, hormone receptors (HR) status and tumor grade are independent prognostic factors for patients with PMBC (p < 0.05). Then we divided 8048 cases into 4 subtypes according to the HR status and tumor grade. The difference in breast cancer specific survival (BCSS) among the four groups was statistically significant. The 5-year BCSS of patients with HR positive and well or moderate differentiated tumor was 97.9%, which was higher than any of other groups. While patients with HR negative and poor differentiated tumor had the worst survival (Table 1). Conclusions: PMBC had favorable biological features and relatively well prognosis. Age, race, tumor size, lymph nodes status, HR status and tumor grade were independent prognostic markers.Subtype divided by HR status and tumor grade was a indicator for prognosis of patients with PMBC. Table1.Outcomes of Four Different Subtypes Subtype 5-year BCSS (%) P value HR positive_well or moderate differentiated 97.9% < 0.001 HR positive_ poor or anaplastic 92.3% HR negative_well or moderate differentiated 96.8% HR negative_ poor or anaplastic 82.1%
Nitric Oxide Production by Myeloid-Derived Suppressor Cells Plays a Role in Impairing Fc Receptor–Mediated Natural Killer Cell Function
Authors: Andrew Stiff, Prashant Trikha, Bethany Mundy-Bosse, Elizabeth McMichael, Thomas A. Mace, Brooke Benner, Kari Kendra, Amanda Campbell, Shalini Gautam, David Abood, Ian Landi, Vincent Hsu, Megan Duggan, Robert Wesolowski, Matthew Old, John Harrison Howard, Lianbo Yu, Nancy Stasik, Thomas Olencki, Natarajan Muthusamy, Susheela Tridandapani, John C. Byrd, Michael Caligiuri, William E. Carson
Journal: Clinical Cancer Research (2018)

Abstract Purpose: mAbs are used to treat solid and hematologic malignancies and work in part through Fc receptors (FcRs) on natural killer cells (NK). However, FcR-mediated functions of NK cells from patients with cancer are significantly impaired. Identifying the mechanisms of this dysfunction and impaired response to mAb therapy could lead to combination therapies and enhance mAb therapy. Experimental Design: Cocultures of autologous NK cells and MDSC from patients with cancer were used to study the effect of myeloid-derived suppressor cells (MDSCs) on NK-cell FcR-mediated functions including antibody-dependent cellular cytotoxicity, cytokine production, and signal transduction in vitro. Mouse breast cancer models were utilized to study the effect of MDSCs on antibody therapy in vivo and test the efficacy of combination therapies including a mAb and an MDSC-targeting agent. Results: MDSCs from patients with cancer were found to significantly inhibit NK-cell FcR-mediated functions including antibody-dependent cellular cytotoxicity, cytokine production, and signal transduction in a contact-independent manner. In addition, adoptive transfer of MDSCs abolished the efficacy of mAb therapy in a mouse model of pancreatic cancer. Inhibition of iNOS restored NK-cell functions and signal transduction. Finally, nonspecific elimination of MDSCs or inhibition of iNOS in vivo significantly improved the efficacy of mAb therapy in a mouse model of breast cancer. Conclusions: MDSCs antagonize NK-cell FcR-mediated function and signal transduction leading to impaired response to mAb therapy in part through nitric oxide production. Thus, elimination of MDSCs or inhibition of nitric oxide production offers a strategy to improve mAb therapy. Clin Cancer Res; 24(8); 1891–904. ©2018 AACR.
Improving Male Reproductive Health After Childhood, Adolescent, and Young Adult Cancer: Progress and Future Directions for Survivorship Research
Authors: Lisa B. Kenney, Zoltan Antal, Jill P. Ginsberg, Bradford S. Hoppe, Sharon L. Bober, Richard N. Yu, Louis S. Constine, Hanneke M. van Santen, Roderick Skinner, Daniel M. Green
Journal: Journal of Clinical Oncology (2018)

Reproductive health is a common concern and often a source of distress for male childhood, adolescent, and young adult cancer survivors. Clinical and epidemiologic research in survivor populations has identified alkylating agent chemotherapy, testicular radiation, and surgery or radiation to the genitourinary organs, lower spine, or the hypothalamic-pituitary region as risk factors for adverse reproductive outcomes, including impaired spermatogenesis, testosterone insufficiency, and sexual dysfunction. Much of the research on male survivors has focused on the outcome of fertility, using spermatogenesis, serum gonadotropins, and paternity as the measures. However, these studies often fail to account for the clinically relevant but difficult-to-quantify aspects of fertility such as sexual function, cancer-related delayed psychosocial development, medical comorbidities, and socioeconomic concerns. Clinical and basic science research has made significant contributions to improving reproductive outcomes for survivors, with recent advancements in the areas of fertility preservation, clinical assessment of reproductive function, and treatment of adverse reproductive outcomes. Furthermore, there is an emerging qualitative literature addressing the psychosexual aspects of male reproductive health, the clinical application of which will improve quality of life for survivors. This review summarizes the current survivorship literature on reproductive health outcomes for male survivors, including the epidemiology of impaired spermatogenesis, testosterone insufficiency, and sexual dysfunction; clinical and laboratory assessment of reproductive function; and established and investigational interventions to preserve reproductive function for patients newly diagnosed and survivors. Although survivorship research has made significant contributions to improving reproductive outcomes, additional scientific progress is needed in the areas of fertility preservation, risk assessment, and psychosexual support with the aim of optimizing reproductive health for current and future survivors.
An increase in LRRK2 suppresses autophagy and enhances Dectin-1–induced immunity in a mouse model of colitis
Authors: Tetsuya Takagawa, Atsushi Kitani, Ivan Fuss, Beth Levine, Steven R. Brant, Inga Peter, Masaki Tajima, Shiro Nakamura, Warren Strober
Journal: Science Translational Medicine (2018)

A LRRK2 inhibitor ameliorates intestinal inflammation in a mouse model of colitis.
Survival prediction in patients treated by FOLFIRI and bevacizumab for metastatic colorectal cancer (PRODIGE 9) using contrast-enhanced CT texture analysis (SPECTRA).
Authors: Anthony Dohan, Benoit Gallix, Boris Guiu, Karine Le Malicot, Caroline Reinhold, Philippe Soyer, Jaafar Bennouna, Francois Ghiringhelli, Valerie Boige, Julien Taieb, Olivier Bouche, Eric Francois, Jean Marc Phelip, Christian Borel, Roger Faroux, Jean-François Seitz, Stephane Jacquot, Come Lepage, Thomas Aparicio, Christine Hoeffel
Journal: Journal of Clinical Oncology (2017)

3601 Background: Quantitative assessment of tumor architecture changes may help to early identify non-responder patients and propose a tailored treatment strategy. Our objective was to build and validate a radiomics signature able to predict early the lack of response to chemotherapy including FOLFIFRI and bevacizumab using baseline and first evaluation CT and to compare it to the RECIST and morphological criteria. Methods: For 230 patients of PRODIGE 9 study and treated by FOLFIRI and bevacizumab, a computed analysis (CA) was performed on the dominant liver lesion (DLL) at baseline and 2 months post-chemotherapy. RECIST evaluation was performed at 2 and 6 months. The sum of the target liver lesions (STL), the density of the DLL, CA parameters and their changes rates were correlated with the 2-year survival status. A radiomics signature combining 3 parameters was built in one arm and validated in the second arm. Survival was estimated with the Kaplan-Meier method and compared with log-rank test. Results: The strongest predictive factors for 2-year survival status were decrease in STL(AUC = .69±.05[95%CI:.60-.77]), change rate in kurtosis(ssf = 0) (AUC = .66±.05[95%CI:.57-.74]), and the baseline density of the DLL (AUC = .68±.05[95%CI:.59-.77]). Using multivariate analysis, predictive factors of 2-year survival status were the decrease in STL &gt; 15%(HR = 1.92, P= .002), the increase in kurtosis value(ssf = 0) &gt; 93% (HR = 2.16, P= .001), and baseline DLL &gt; 64.3UH (HR = 1.70, P= .02). Then, the SPECTRA-score was built by according 1 point for each of the 3 criteria. Patients with a SPECTRA-score &gt; 1 had a lower overall survival in the training ( P= .001) and in the validation cohort ( P= .002). Non-response according to RECIST at 6 months had the same prognostic value as SPECTRA-score&gt;1 at 2 months. Conclusions: A radiomics signature combining STL, density and CA on baseline and first evaluation CT is be able to predict which patient will have a poor outcome with same performances than standard evaluation with RECIST1.1 at 6 months in mCRC patients. Clinical trial information: NCT00952029.
Abstract 17189: Indications and Adverse Effects of Statin Therapy in Children: A Retrospective Electronic Medical Record Review
Authors: Christopher Prendergast, Irene Predazzi, Laura Wiley, Jessica Lilley, Sara Van Driest, Sergio Fazio, Tracy McGregor
Journal: Circulation (2016)

Introduction:  Statins are the most commonly prescribed medications for primary and secondary prevention of coronary artery disease and stroke. Adverse drug reactions (ADRs) ranging from common myalgia to rhabdomyolysis with renal failure can occur. The indications for statin therapy and prevalence of statin ADRs in pediatrics have not been well described.   Hypothesis:  Statin ADRs occur less commonly in pediatric patients than in adults.   Methods:  Using electronic medical record (EMR) data, we abstracted charts of young subjects for whom statins were prescribed at Vanderbilt University Medical Center. We included 276 subjects with statin therapy initiated ≤21 years. Each record was reviewed manually for therapy indication, age at initiation, drug, dose(s), and reports of ADRs.   Results:  The most common indication for statin prescription in children was hypercholesterolemia, followed by renal disease, type 1 diabetes, and heart transplant. Only 10/276 (3.6%) subjects reported ADR to statins leading to a therapeutic change, lower than the 10-25% estimates from observational studies in adults. No pediatric patients were identified with rhabdomyolysis.   Conclusions:  ADRs during statin therapy in young patients are infrequent, mostly characterized by mild skeletal muscle symptoms, and rarely result in a change to statin therapy. The risk-to-benefit evaluation of using statin therapy in pediatrics with diverse indications appears favorable with regard to the incidence of skeletal muscle symptoms. However, our analysis does not address other concerns such as hormonal signaling in adolescent patients during times of rapid growth and pubertal development.