tbuckley/cabot-search huggingface dataset:
A20/TNFAIP3 Regulates the DNA Damage Response and Mediates Tumor Cell Resistance to DNA-Damaging Therapy
Authors: Chuanzhen Yang, Weicheng Zang, Zefang Tang, Yapeng Ji, Ruidan Xu, Yongfeng Yang, Aiping Luo, Bin Hu, Zemin Zhang, Zhihua Liu, Xiaofeng Zheng
Journal: Cancer Research (2017)

Abstract A competent DNA damage response (DDR) helps prevent cancer, but once cancer has arisen, DDR can blunt the efficacy of chemotherapy and radiotherapy that cause lethal DNA breakage in cancer cells. Thus, blocking DDR may improve the efficacy of these modalities. Here, we report a new DDR mechanism that interfaces with inflammatory signaling and might be blocked to improve anticancer outcomes. Specifically, we report that the ubiquitin-editing enzyme A20/TNFAIP3 binds and inhibits the E3 ubiquitin ligase RNF168, which is responsible for regulating histone H2A turnover critical for proper DNA repair. A20 induced after DNA damage disrupted RNF168–H2A interaction in a manner independent of its enzymatic activity. Furthermore, it inhibited accumulation of RNF168 and downstream repair protein 53BP1 during DNA repair. A20 was also required for disassembly of RNF168 and 53BP1 from damage sites after repair. Conversely, A20 deletion increased the efficiency of error-prone nonhomologous DNA end-joining and decreased error-free DNA homologous recombination, destablizing the genome and increasing sensitivity to DNA damage. In clinical specimens of invasive breast carcinoma, A20 was widely overexpressed, consistent with its candidacy as a therapeutic target. Taken together, our findings suggest that A20 is critical for proper functioning of the DDR in cancer cells and it establishes a new link between this NFκB-regulated ubiquitin-editing enzyme and the DDR pathway. Significance: This study identifies the ubiquitin-editing enzyme A20 as a key factor in mediating cancer cell resistance to DNA-damaging therapy, with implications for blocking its function to leverage the efficacy of chemotherapy and radiotherapy. Cancer Res; 78(4); 1069–82. ©2017 AACR.
Myeloid Growth Factors, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology
Authors: Jeffrey Crawford, Pamela Sue Becker, James O. Armitage, Douglas W. Blayney, Julio Chavez, Peter Curtin, Shira Dinner, Thomas Fynan, Ivana Gojo, Elizabeth A. Griffiths, Shannon Hough, Dwight D. Kloth, David J. Kuter, Gary H. Lyman, Mary Mably, Sudipto Mukherjee, Shiven Patel, Lia E. Perez, Adam Poust, Raajit Rampal, Vivek Roy, Hope S. Rugo, Ayman A. Saad, Lee S. Schwartzberg, Sepideh Shayani, Mahsa Talbott, Saroj Vadhan-Raj, Sumithira Vasu, Martha Wadleigh, Peter Westervelt, Jennifer L. Burns, Lenora Pluchino
Journal: Journal of the National Comprehensive Cancer Network (2017)

Myeloid growth factors (MGFs) are given as supportive care to patients receiving myelosuppressive chemotherapy to reduce the incidence of neutropenia. This selection from the NCCN Guidelines for MGFs focuses on the evaluation of regimen- and patient-specific risk factors for the development of febrile neutropenia (FN), the prophylactic use of MGFs for the prevention of chemotherapy-induced FN, and assessing the risks and benefits of MGF use in clinical practice.
Phase 2 Study of the HSP-90 Inhibitor AUY922 in Previously Treated and Molecularly Defined Patients with Advanced Non–Small Cell Lung Cancer
Authors: Enriqueta Felip, Fabrice Barlesi, Benjamin Besse, Quincy Chu, Leena Gandhi, Sang-We Kim, Enric Carcereny, Lecia V. Sequist, Paal Brunsvig, Christos Chouaid, Egbert F. Smit, Harry J.M. Groen, Dong-Wan Kim, Keunchil Park, Emin Avsar, Sebastian Szpakowski, Mikhail Akimov, Edward B. Garon
Journal: Journal of Thoracic Oncology (2017)
Abstract A22: Identifying serum biomarkers for colorectal cancer using immunoproteomics
Authors: Muneerah Smith, Jonathan M. Blackburn
Journal: Cancer Research (2017)

Abstract The Blackburn lab has developed a highly sensitive and selective native cancer-antigen (CT100+) microarray, which has been used to detect autoantibodies in the blood samples of cancer patients. Although technically advanced, the microarray has biological limitations as we observe a random antibody response in 10-20% of patients with various cancer-types. Our aim is therefore to use immunoproteomics to identify tumor specific antigens (TSAs) which can reproducibly be used for cancer diagnosis and prognosis. We have an archive of 67 cancer and paired normal tissues, with corresponding autologous blood plasma samples, from patients with colorectal cancer (CRC) (Groote Schuur Hospital, South Africa) for identifying novel TSAs. For each patient, we have a set of clinical information which can be used to identify cancer antigens associated with disease pathogenesis. To identify novel cancer antigens, we have developed an immuno-pulldown assay, in which Protein A and Protein G magnetic microbeads are used to selectively capture antibodies from the patient blood plasma. The Ig-bound microbeads were incubated with native cancer and control tissue lysates to capture antigens. After performing an on-bead tryptic digestion, the peptides were eluted and proteins were identified by mass spectrometry, using a Q-Exactive mass analyser. Using the MaxQuant proteomics software, we were able to identify a total of 1276 proteins, of which 360 were unique to the cancer samples. Eight of the 360 cancer-unique proteins were matched to the Tantigen database, a data source and analysis platform for cancer vaccine target discovery. Furthermore, 3 of the 8 proteins identified have been reported to induce antibody responses in cancer patients. In conclusion, we have developed an immuno-pulldown assay that captures and identifies proteins which are unique to cancer tissues, of which several have shown to induce a T- and B-cell response in cancer patients. Although we are able to identify protein candidates of interest, we observe several limitations with the assay, for which we are currently troubleshooting. Once the method is optimized, the newly identified TSAs will be fabricated on to the CT100+ microarray, and validated with patient sera to confirm the presence of cancer-specific antibody response. Citation Format: Muneerah Smith, Jonathan M. Blackburn. Identifying serum biomarkers for colorectal cancer using immunoproteomics [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A22.
Decreasing Blood Pressure in Older Patients
Authors: James S. Goodwin
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine 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 Internal Medicine journal
THE EFFECTS OF EXERCISE
Journal: JAMA (1933)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 60: Characterization of papillary thyroid carcinoma primary cell culture derived cancer stem-like cells
Authors: Alfred Simental, Steve Lee, Pedro A. De Andrade Filho, Nathaniel R. Peterson, Saied Mirshahidi, Penelope Duerksen-Hughes, Xiangpeng Yuan
Journal: Clinical Cancer Research (2017)

Abstract Papillary thyroid carcinoma is the most frequent type of thyroid cancer. Although most PTC patients can be treated successfully and have an excellent prognosis, 10-20% of patients with stage I/II disease experience recurrence, developing invasive tumors and/or distant metastases. For these patients, a greater understanding of the mechanisms that govern PTC tumor initiation and progression would aid in developing effective therapeutic strategies to target the disease. It is becoming evident that thyroid tumors may follow the cancer stem cell model (CSC), where a population of cancer stem cells is responsible for tumor initiation and progression. Currently, the CSC biology of PTC is still poorly understood. In this study, we isolated sphere-growing cells from PTC specimen-derived primary cells using serum-free culture. In vivo transplantation analysis revealed that the sphere cells were capable of generating xenograft tumors that recapitulated the original tumor phenotypes. Analyzing the sphere cells for aldehyde dehydrogenase (ALDH) expression, a marker commonly used in CSC study, revealed that around half of the sphere cells did not express ALDH. When the sphere cells were sorted into ALDH- and ALDH+ subpopulations, both subpopulations demonstrated capabilities of re-initiating subspheres in vitro and generating serial xenograft tumors in vivo with the ALDH+ cells exhibiting a slightly higher efficiency of sphere-formation and cancer-initiation. Of major importance, the sphere cell population without sorting demonstrated the higher levels of cancer-initiating cell frequency, and quicker xenograft tumor progression than the subpopulations of ALDH- and ALDH+ cells. Furthermore, histologic investigation of xenograft tumors generated by the sphere population and the sphere-sorted subpopulations, respectively, revealed similar morphological features that recapitulated the characteristics of original human PTC from which the sphere cells were isolated. Our data established a vital role of ALDH- cancer stem-like cells and revealed a potential synergistic activity between ALDH- and ALDH+ cells in the tumor initiation and progression of PTC. Further exploring the biological property of ALDH- cancer stem-like cells may lead to development of novel therapeutic solutions to treating aggressive PTC. Citation Format: Alfred Simental, Steve Lee, Pedro A. De Andrade Filho, Nathaniel R. Peterson, Saied Mirshahidi, Penelope Duerksen-Hughes, Xiangpeng Yuan. Characterization of papillary thyroid carcinoma primary cell culture derived cancer stem-like cells [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 60.
Radiofrequency Denervation for Chronic Low Back Pain
Authors: Ming-Chih Kao, Michael S. Leong, Sean Mackey
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update
Authors: Sandra L. Wong, Mark B. Faries, Erin B. Kennedy, Sanjiv S. Agarwala, Timothy J. Akhurst, Charlotte Ariyan, Charles M. Balch, Barry S. Berman, Alistair Cochran, Keith A. Delman, Mark Gorman, John M. Kirkwood, Marc D. Moncrieff, Jonathan S. Zager, Gary H. Lyman
Journal: Journal of Clinical Oncology (2017)

Purpose To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma. Methods An ASCO-SSO panel was formed, and a systematic review of the literature was conducted regarding SLN biopsy and completion lymph node dissection (CLND) after a positive sentinel node in patients with melanoma. Results Nine new observational studies, two systematic reviews, and an updated randomized controlled trial of SLN biopsy, as well as two randomized controlled trials of CLND after positive SLN biopsy, were included. Recommendations Routine SLN biopsy is not recommended for patients with thin melanomas that are T1a (nonulcerated lesions < 0.8 mm in Breslow thickness). SLN biopsy may be considered for thin melanomas that are T1b (0.8 to 1.0 mm Breslow thickness or < 0.8 mm Breslow thickness with ulceration) after a thorough discussion with the patient of the potential benefits and risk of harms associated with the procedure. SLN biopsy is recommended for patients with intermediate-thickness melanomas (T2 or T3; Breslow thickness of > 1.0 to 4.0 mm). SLN biopsy may be recommended for patients with thick melanomas (T4; > 4.0 mm in Breslow thickness), after a discussion of the potential benefits and risks of harm. In the case of a positive SLN biopsy, CLND or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathological factors. For higher-risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND. Important qualifying statements outlining relevant clinicopathological factors and details of the reference patient populations are included within the guideline. Additional information is available at www.asco.org/melanoma-guidelines and www.asco.org/guidelineswiki .
Tendências das infecções meningocócicas do grupo C, na República da Irlanda
Authors: J Fogarty
Journal: Eurosurveillance (1997)

Em Novembro de 1994, foi estabelecido um sistema nacional de vigilância microbiologica para as infeccoes meningococicas, na Republica da Irlanda (RI). Os formularios de recolha dos dados sao devolvidos, mensalmente, ao centro, quer tenham ou nao ocorrido casos, com um numero minimo de dados (nome, data de nascimento, data do isolamento, local do isolamento, serogrupo, tipo e sub-tipo se disponiveis e resultado vital).
High-Cutoff Hemodialysis in Myeloma Cast Nephropathy
Authors: Kenar D. Jhaveri, Ruben Niesvizky
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
OC-007 Enhancing detection and treatment of viral hepatitis and liver fibrosis in vulnerable and homeless adults through dedicated hostel-based liver service: valid (vulnerable adults liver disease) study
Authors: A Hashim, L Macken, T Worthley, GP Aithal, S Verma
Journal: Gut (2017)

Introduction  Homeless adults, a disenfranchised and stigmatised cohort, are particularly at risk of chronic liver disease (CLD) due to high prevalence of alcohol/substance misuse. Risk of CLD rises further with increasing age. However, this vulnerable group don’t engage with or access hospital services. We have designed a community liver service in Southeast England, with an aim of detecting, staging and treating CLD in homeless adults aged > 40 years.  Method  In October 2015, we set up a new service at two major homeless hostels and a primary care practice that caters to the homeless. As a part of prospective cohort study, we enrolled consecutive aged >40 years. Each individual was offered alcohol (AUDIT questionnaire) and substance misuse assessment, blood borne virus (BBV) tests and mobile Transient Elastography (TE). Clinically significant hepatic fibrosis (CSHF) was defined as liver stiffness measurement (LSM) ≥8 kPa  Results  Till date 71 individuals have been enrolled. Mean age of participants was 51 years±5.8%–82% were males. Forty one (58%) were homeless or living in hostels at the time of recruitment. Positive hepatitis C virus (HCV) antibody was detected in 28 participants (39.4%), while HIV antibody and hepatitis B core antibody were found in 2 (2.8%) and 12 participants (17%) respectively. Twenty six out of 28 (93%) individuals with positive HCV antibody consented to further testing, twenty (77%) having a positive HCV PCR. The prevailing genotypes were 1a (55%) and 3a (45%). The majority (75%) were drinking alcohol in excess of recommended guidelines, the AUDIT questionnaire revealing that 33 individuals (46%) had alcohol dependence (scores of >20/40). Fifty seven (80%) had history of current/past substance misuse with 24 (66%) individuals having a formal diagnosis of mental illness. Of the 71 participants, 22 (31%) had CSHF (LSM ≥8 kPa) with 13 (18%) having advanced fibrosis (LSM > 13 kPa. The main aetiologies for CLD were alcohol, HCV or both. Of the 20 individuals with positive HCV RNA, five commenced community based HCV treatment with direct acting antivirals with two more currently being worked up for therapy.  Conclusion  Preliminary results of the VALID study show a high prevalence chronic HCV infection and CSHF in vulnerable/homeless people over 40 years of age. We found an excellent uptake of community based liver service from this group and mobile TE was perceived as a powerful tool to facilitate engagement. Our initial results endorse the success of this easy to replicate community model of liver care for vulnerable adults.  Disclosure of Interest  A. Hashim: None Declared, L. Macken: None Declared, T. Worthley: None Declared, G. P. Aithal: None Declared, S. Verma Conflict with: Dunhill Medical Trust, Gilead
miR-204-5p and miR-211-5p Contribute to BRAF Inhibitor Resistance in Melanoma
Authors: Marta Díaz-Martínez, Lucía Benito-Jardón, Lola Alonso, Lisa Koetz-Ploch, Eva Hernando, Joaquin Teixidó
Journal: Cancer Research (2017)

Abstract Melanoma treatment with the BRAF V600E inhibitor vemurafenib provides therapeutic benefits but the common emergence of drug resistance remains a challenge. We generated A375 melanoma cells resistant to vemurafenib with the goal of investigating changes in miRNA expression patterns that might contribute to resistance. Increased expression of miR-204-5p and miR-211-5p occurring in vemurafenib-resistant cells was determined to impact vemurafenib response. Their expression was rapidly affected by vemurafenib treatment through RNA stabilization. Similar effects were elicited by MEK and ERK inhibitors but not AKT or Rac inhibitors. Ectopic expression of both miRNA in drug-naïve human melanoma cells was sufficient to confer vemurafenib resistance and more robust tumor growth in vivo. Conversely, silencing their expression in resistant cells inhibited cell growth. Joint overexpression of miR-204-5p and miR-211-5p durably stimulated Ras and MAPK upregulation after vemurafenib exposure. Overall, our findings show how upregulation of miR-204-5p and miR-211-5p following vemurafenib treatment enables the emergence of resistance, with potential implications for mechanism-based strategies to improve vemurafenib responses. Significance: Identification of miRNAs that enable resistance to BRAF inhibitors in melanoma suggests a mechanism-based strategy to limit resistance and improve clinical outcomes. Cancer Res; 78(4); 1017–30. ©2017 AACR.