tbuckley/cabot-search huggingface dataset:
Molecular pathogenic pathways in extranodal NK/T cell lymphoma
Authors: Sanjay de Mel, Susan Swee-Shan Hue, Anand D. Jeyasekharan, Wee-Joo Chng, Siok-Bian Ng
Journal: Journal of Hematology & Oncology (2019)

Extranodal NK/T cell lymphoma, nasal type (ENKTL) is an aggressive malignancy with a dismal prognosis. Although l-asparaginase-based chemotherapy has resulted in improved response rates, relapse occurs in up to 50% of patients with disseminated disease. There is hence an urgent need for effective targeted therapy, especially for patients with relapsed or refractory disease. Novel insights gleaned from high-throughput molecular and genomic profiling studies in recent years have contributed significantly to the understanding of the molecular biology of ENKTL, which exemplifies many of the hallmarks of cancer. Deregulated pro-proliferative signaling pathways, such as the Janus-associated kinase/signal transducer and activator of transcription (JAK/STAT), platelet-derived growth factor (PDGF), Aurora kinase, MYC, and NF-κB, have been identified as potential therapeutic targets. The discovery of the non-canonical function of EZH2 as a pro-proliferative transcriptional co-activator has shed further light on the pathogenesis of ENKTL. Loss of key tumor suppressor genes located on chromosome 6q21 also plays an important role. The best-studied examples include PR domain zinc finger protein 1(PRDM1), protein tyrosine phosphatase kappa (PTPRK), and FOXO3. Promoter hypermethylation has been shown to result in the downregulation of other tumor suppressor genes in ENKTL, which may be potentially targeted through hypomethylating agents. Deregulation of apoptosis through p53 mutations and upregulation of the anti-apoptotic protein, survivin, may provide a further growth advantage to this tumor. A deranged DNA damage response as a result of the aberration of ataxia telangiectasia-related (ATR) kinases can lead to significant genomic instability and may contribute to chemoresistance of ENKTL. Recently, immune evasion has emerged as a critical pathway for survival in ENKTL and may be a consequence of HLA dysregulation or STAT3-driven upregulation of programmed cell death ligand 1 (PD-L1). Immunotherapy via inhibition of programmed cell death 1 (PD-1)/PD-L1 checkpoint signaling holds great promise as a novel therapeutic option. In this review, we present an overview of the key molecular and pathogenic pathways in ENKTL, organized using the framework of the "hallmarks of cancer" as described by Hanahan and Weinberg, with a focus on those with the greatest translational potential.
Abstract 3348: Pax8-PPARδ fusion protein activates β-catenin/TCF pathways
Authors: Dang L. Vu-Phan, Jingcheng Yu, Ronald J. Koenig, Max S. Wicha
Journal: Cancer Research (2012)

Abstract Pax8-PPARδ Fusion Protein (PPFP) occurs in ∼35% of follicular thyroid carcinomas. Expression of PPFP in the non-transformed rat thyroid cell line PCCL3 conferred on the cells the ability to invade through matrigel and to form colonies in anchorage independent conditions. PPFP also increased the percentage of cells that have activated β-catenin/TCF. We transfected control and PPFP expressing PCCL3 thyroid cell lines with two different β-catenin/TCF-GFP reporter systems. We then sorted a population of GFP positive cells and expanded them to obtain 100% transfected cell lines. These GFP positive cells gave rise to a new heterogenous population with a stable equilibrium between GFP positive, β-catenin/TCF active cells and GFP negative, β-catenin/TCF inactive cells. PPFP expressing cell lines contained more than twice the percentage of GFP positive cells compared to control cell lines. GFP positive PPFP expressing thyroid cells were enriched for cells exhibiting the transformed phenotypes previously observed in the unsorted, untransfected cell lines. Sorted β-catenin/TCF active single cells gave rise to heterogenous clonal populations containing both β-catenin/TCF active and negative cells. Clonal populations derived from β-catenin/TCF inactive cells remained purely negative. Clonal populations derived from GFP positive cells were twice as enriched for anchorage independent colony forming cells than GFP negative clones. More strikingly, GFP positive clones were 5-10 times more invasive than negative clones, which exhibited the same invasive potential as control cells. Treatment with PPARδ full or partial agonists further increased the β-catenin/TCF population in PPFP expressing cells. Again, the effects were confined to populations containing β-catenin/TCF active cells. Co-treatment with PPARδ antagonists reversed the effects of PPARδ agonists. These data suggest that β-catenin/TCF active cells have properties of cancer stem cells and that PPFP acts on this population to expand the stem cell like fraction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3348. doi:1538-7445.AM2012-3348
First UK private medical school degree delayed following GMC concerns
Authors: Matthew Billingsley
Journal: BMJ (2014)

A private medical school degree course that was due to start in September 2014 has been delayed by a year after a review by the General Medical Council.

The University of Central Lancashire (UCLan) planned to charge students £35 000 (€44 640; $57 350) a year for its five year MB BS Bachelor of Medicine and Bachelor of Surgery degree. It would have been the first privately funded medical course to open in the UK.

However, the GMC has expressed concerns about the “arrangements in place for the selection of students, the curriculum coherence and structure, assessment and quality management” in a report about the preparedness of the school.1

The regulator …
When I’m 64 (Slices)—Prognostication in Geriatric Trauma
Authors: Areti Tillou, Jonathan R. Hiatt
Journal: JAMA Surgery (2019)

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 Surgery 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 Surgery journal
Co-delivery of TRAIL and siHSP70 using hierarchically modular assembly formulations achieves enhanced TRAIL-resistant cancer therapy
Authors: Anwei Zhou, Junjie Du, Mengying Jiao, Daping Xie, Qianqian Wang, Lingjing Xue, Caoyun Ju, Zichun Hua, Can Zhang
Journal: Journal of Controlled Release (2019)
Abstract P3-12-17: Intraoperative radiotherapy (IORT) after neoadjuvant chemotherapy in patients with breast cancer– Experience in the Cancer Institute of Lima-Peru
Authors: JM Cotrina, JA Galarreta, MA Pinillos, S Vilchez
Journal: Cancer Research (2019)

Abstract Background Intraoperative radiotherapy (IORT) is a treatment technique that allows the surgical bed to be irradiated in the same surgical act after breast-conserving surgery, in some cases as a single treatment and in others as a boost complemented with external radiotherapy. There are studies that have shown their non-inferiority with respect to conventional external radiotherapy, taking advantage of administration time, costs and side effects. Methods In this study, the IORT (INTRABEAM) was used as treatment in patients who received neoadjuvant treatment with chemotherapy who had a good response and met the criteria to be included (no tumor or tumors less than 3 cm, unifocal tumors, no skin involvement after treatment). Out of a total of 255 cases of IORT performed in recent years, 42 were studied, those who received neoadjuvant chemotherapy from April 2014 to April 2018 and who completed the treatment. Results The average age was 47.9 years (29-72), 59.5% were between 40-49 years old and 11.4% were under 40 years old. 61.9% were stage II and 38.1% stage III. The diameter of the most used applicator was between 3-3.5 cm (56.8%) and the average irradiation time was 20 mins (12-46 mins). All received external RT. 67.6% received on average 25 sessions and 32.4% received 15 sessions. There were 64.2% luminal (luminal A 7.1%, luminal B 38.1%, luminal B HER2 (+) 19%), 7.1% with ER/PR(-) HER2(+) and 28.6% ER/PR(-) HER2(-). 38% patients had complete pathological response in the primary tumor. Of the 42 patients treated, 37 had a follow-up of more than 6 months. 3 (7.1%) had recurrence, 2 local and 1 local and distant (EC IIIC). Disease-free survival at 12, 24 and 36 months was 97.2%, 90.5% and 90.5% and the overall survival was 100%, 100% and 92.3% respectively. Clinical Stages / ImmunophenotypesClinical StagesN (%)ImmunophenotypeN (%)IIA12(28.6)Luminal A3(7.1)IIB14(33.3)Luminal B16(38.1)IIIA7(16.7)Luminal B HER2(+)8(19.0)IIIB8(19.0)ER/PR(-) HER2(+)3(7.1)IIIC1(2.4)ER/PR(-)HER2(-)12(28.6) Disease Free SurvivalMonths122436DFS97.2%90.5%90.5% Conclusion The IORT (INTRABEAM) used as a boost in patients with breast cancer and neoadjuvant treatment who complete complementary external RT, is a safe procedure, with low recurrence rate, it is easy to perform with a good tolerance, shorter time of treatment and with fewer side effects. Citation Format: Cotrina JM, Galarreta JA, Pinillos MA, Vilchez S. Intraoperative radiotherapy (IORT) after neoadjuvant chemotherapy in patients with breast cancer– Experience in the Cancer Institute of Lima-Peru [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-17.
How to fill in and interpret an observation chart
Authors: Marina Soltan, Rachel Westacott
Journal: BMJ (2017)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following How to fill in and interpret an observation chart Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Abstract P5-03-09: LINC00624 binding with SFPQ/MATR3/ NONO protein complexes enhances resistance to neoadjuvant therapy in HER-2 positive breast cancer by inhibiting tumor immune response
Authors: Q Zhang, B Xiu, Y Chi, W-R Chi, J Wu
Journal: Cancer Research (2019)

Abstract Background Neoadjuvant chemotherapy(NAC) has been widely used for its ability to downstage breast cancer. With anti-HER2 therapy, around half of the HER2 positive patients achieve pCR after NAC. However, treatment failure is still a concern and leads to a worse prognosis. New biomarkers and biological mechanisms are waiting to be discovered to tackle this problem. Methods RNA-Seq was performed to identify differently expressed RNAs between pCR and non-pCR group. The IC50 value was measured by CCK-8 assay in HER-2 positive cells (SK-BR-3 and JIMT-1). Quantitative RT-PCR (qRT-PCR) was used to detect the expression levels of LINC00624 and its potential target genes. RNA-seq and GSEA analysis was carried out to determine the target pathways regulated by LINC00624. Results Core needle biopsy tissue from HER-2 positive patients was collected before NAC. LINC00624 was found to be down regulated in pCR group compared with non-pCR group by RNA-seq. High expression of LINC00624 was associated with poor overall survival in TCGA database and our own patients cohort. Overexpression of LINC00624 promoted cell proliferation and colony-forming ability. Meanwhile, the IC50 values of Paclitaxel and Trastuzumab in HER-2 positive breast cells were decreased by LINC00624. Via RNA pull-down assay and mass spectrometry, the SFPQ/MATR3/NONO protein complex, which was reported to be associated with the innate immune system, was found to interact with LINC00624. RNA-seq further revealed that several immunological and inflammatory factors, including 'IFN-α response', 'IFN-γ response' and 'TNF-α via NF-κB' were suppressed by LINC00624. IFN downstream molecules were inactivated in LINC00624 overexpressing cells following TNF-α, IFN-α, IFN-β and poly (I:C) treatment, which implies the immune inhibition ability of LINC00624 . Conclusion LINC00624 is associated with resistance to NAC in HER-2 positive breast cancer. It binds with the SFPQ/MATR3/NONO complex and desensitizes cell response to chemotherapy and anti-HER2 agents via suppressing immunological and inflammatory effect. This study suggests that LINC00624 could serve as a biomarker to predict therapy response to NAC in HER-2 positive breast cancer. Citation Format: Zhang Q, Xiu B, Chi Y, Chi W-R, Wu J. LINC00624 binding with SFPQ/MATR3/ NONO protein complexes enhances resistance to neoadjuvant therapy in HER-2 positive breast cancer by inhibiting tumor immune response [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-03-09.
Abstract B01: Lymphangiogenic gene expression is associated with lymph node recurrence and poor survival after hepatectomy for colorectal liver metastases
Authors: Thomas Vellinga, Dieuwke Marvin, Inne Borel Rinkes, Jeroen Hagendoorn, Onno Kranenburg
Journal: Cancer Research (2016)

Abstract Expression of the lymphangiogenic growth factors, in particular VEGF-C, are correlated with disease-free and overall survival in primary colorectal cancer (CRC). Moreover, in patients with metastatic CRC (mCRC) lymphatic invasion and lymph node metastases are correlated with worse outcome, but the biology underlying these correlations remains unknown. To study a potential relationship between tumor biology, lymphatic spread from liver metastases and outcome, we compiled a lymph-endothelium gene set the lymphangiogenesis signature comprised of six genes specifically expressed by lymph endothelial cells, or growth factors stimulating them. In primary colorectal cancer, expression of this signature correlated with increased risk of distant metastasis. When used to cluster a cohort of 119 colorectal liver metastases (CRLM) based on gene expression profiles, the signature identified an aggressive poor prognosis subtype of CRLM with mesenchymal gene expression and a stem-like tumor phenotype. RTqPCR analysis of CRLMs with and without lymph node recurrence during follow up showed that VEGF-C and neuropilin-2 were significantly higher expressed by CRLM with onward spread to the lymph nodes. We conclude that CRLM expressing high levels of lymphangiogenic genes are more likely to develop lymph node metastases during follow up and that this correlates with a general aggressive tumor biology (i.e. the mesemcnymal/stem-like phenotype) and poor survival. Post liver resection adjuvant therapy targeting onward spread to the lymph nodes may be beneficial for patients with mesenchymal-type mCRC. Citation Format: Thomas Vellinga, Dieuwke Marvin, Inne Borel Rinkes, Jeroen Hagendoorn, Onno Kranenburg. Lymphangiogenic gene expression is associated with lymph node recurrence and poor survival after hepatectomy for colorectal liver metastases. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B01.
Welcome to the grindstone
Authors: Isobel Weinberg
Journal: BMJ (2012)

Summer is fading fast, and a new academic year looms. As medical students wipe dust from battered textbooks and shuffle reluctantly back to lecture halls and wards, they will be experiencing a mix of emotions. A new term brings excitement, optimism, but also—for some—apprehension at returning to the grind. We all know how taxing the demands of medical training and clinical practice can be. The statistics are shocking but no longer surprising: healthcare workers have higher rates of depression than other professionals; one in 15 doctors experiences drug or alcohol dependence at some point.

How …
The class ceiling for tomorrow’s junior doctors
Authors: Joseph O’Keeffe
Journal: BMJ (2016)

As junior doctors fight to hold on to their terms and conditions, I worry about my own situation and that of future medical students. A medical degree now costs on average £45 000 (€58 240; $64 650) in tuition fees, plus £30 000 in maintenance payments. Grants and bursaries have been frozen or withdrawn and replaced with static loans. Three private medical schools will be operating by 2017, yet the foundation programme was oversubscribed in January 2015 for the fifth year in a row.1 Medical school summer vacations, once reserved for recuperation and overdraft repayment, are now for CV padding: unpaid internships or shadowing. How many 17 year olds have the bravado to take on a medical degree or the parents to fund it?

In 2012, the year tuition fees were trebled, the Social Mobility and Child Poverty Commission announced that medicine “lags behind other professions” in the focus and …
Abstract P2-03-04: A novel druggable target upstream of Notch: MEK5/ERK5 signaling regulates Jagged-1 and Notch1 expression in triple negative breast cancer stem cells
Authors: DA Ucar, MD Matossian, VT Hoang-Barnes, FM Hossain, M Gupta, HE Burks, TD Wright, J Cavanaugh, P Flaherty, ME Burow, L Miele
Journal: Cancer Research (2019)

Abstract Triple negative breast cancer (TNBC) is a molecularly heterogeneous, clinically aggressive disease group that is highly prevalent among African-Americans and younger patients. Standard chemo/radio therapy often produces clinical responses, but recurrence and metastasis are unfortunately common. Metastatic disease is generally incurable. Chemo/radiotherapy has been shown to induce EMT and enrich a chemo-resistant cancer stem-like cell (CSC) population in TNBC. CSCs are thought to drive disease recurrence. Notch signaling is critical for maintenance of TNBC CSC. Expression of Notch1 and its ligand Jagged1 are correlated with poor prognosis. Efforts to pharmacologically target Notch with Gamma Secretase Inhibitors (GSIs) have been impaired by the systemic toxicity of the GSIs, and by the fact that Notch1 also plays a key role in anti-tumor adaptive immunity. Therapeutic agents that indirectly and selectively target Notch signaling in breast cancer cells would be a potentially attractive strategy. However, no such agents have been identified to date. We have found that the MAPK5-ERK5 kinase pathway, which contains at least two druggable targets, functions as a master regulator of Notch signaling in TNBC cells. ERK5 knockout TNBC cells have dramatically decreased expression of Notch receptors, ligands and transcriptional targets. In vivo, these cells form barely detectable tumors that do not metastasize and express lower levels of Notch1 and its ligand Jagged1. Using in silico screening, we identified a class of compounds that selectively target MAP2K5 (MEK5) and decrease the phosphorylation of MAPK7 (ERK5). We selected compound SC-181 for further study. Consistent with ERK5KO cells, pharmacological suppression of ERK5 phosphorylation with SC-181 decreased Notch1 and Jagged1 mRNAs and proteins. SC-181 reversed EMT and reduced the CD44hi/CD24lo CSC population in TNBC cells, but had no effect on T-cell proliferation. SC-181 decreased the number and size of mammospheres in a concentration-dependent manner. Overexpression of the Notch1 intracellular domain (N1IC) in ERK5KO cells rescues their phenotype, dramatically increasing the CSC fraction and promoting EMT. Our results suggest that targeting the MEK5-ERK5 pathway is a promising new strategy to selectively modulate Notch signaling in TNBC CSC without compromising tumor immunity. Citation Format: Ucar DA, Matossian MD, Hoang-Barnes VT, Hossain FM, Gupta M, Burks HE, Wright TD, Cavanaugh J, Flaherty P, Burow ME, Miele L. A novel druggable target upstream of Notch: MEK5/ERK5 signaling regulates Jagged-1 and Notch1 expression in triple negative breast cancer stem cells [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-03-04.
Interpreting arterial blood gases
Authors: Anna Fraser, Yee Ean Ong
Journal: BMJ (2012)

Objective  This study explores the use of quantitative data on strength and fatigability of orofacial muscles in patients with facioscapulohumeral muscular dystrophy (FSHD) and assesses the frequency of swallowing and communication difficulties and their relationship to orofacial muscle involvement.  Methods  We included 43 patients with FSHD and 35 healthy controls and used the Iowa Oral Performance Instrument (IOPI) to obtain quantitative measurements of strength and endurance of lip compression, cheek (buccodental) compression, and tongue elevation. For the assessment of swallowing and communication difficulties, we used the dysphagia-specific quality of life (SWAL-QOL) and Communicative Participation Item Bank questionnaires.  Results  Cheek compression strength was reduced in patients with FSHD compared to healthy controls. Dysphagia and difficulty with verbal communication were reported by 25% and 35% of patients, respectively, and correlated to cheek compression strength and endurance and to anterior tongue elevation endurance. Prolonged cheek compression or anterior tongue elevation endurance (decreased fatigability) made swallowing or speech problems less likely to occur.  Conclusion  Cheek compression strength is the most sensitive IOPI measure for orofacial weakness in FSHD. Orofacial weakness contributes to dysphagia and speech difficulties in FSHD, which are both common, though generally mild. Higher endurance of orofacial muscles was associated with a lower chance of dysphagia or speech problems. More research is required for further refinement of the pattern of facial muscle involvement in FSHD and to provide new insights for improvement of speech and language therapy.
Abstract P3-04-02: Not presented
Authors: X Chen, Y Tong, W Chen, Y Li, K Shen
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Chen X, Tong Y, Chen W, Li Y, Shen K. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-04-02.