tbuckley/cabot-search huggingface dataset:
COP9 Signalosome Controls the Degradation of Cytosolic Misfolded Proteins and Protects Against Cardiac Proteotoxicity
Authors: Huabo Su, Jie Li, Hanming Zhang, Wenxia Ma, Ning Wei, Jinbao Liu, Xuejun Wang
Journal: Circulation Research (2015)

Impaired degradation of misfolded proteins is associated with a large subset of heart diseases. Misfolded proteins are degraded primarily by the ubiquitin-proteasome system, but the ubiquitin ligases responsible for the degradation remain largely unidentified. The cullin deneddylation activity of the COP9 signalosome (CSN) requires all 8 CSN subunits (CSN1 through CSN8) and regulates cullin-RING ligases, thereby controlling ubiquitination of a large number of proteins; however, neither CSN nor cullin-RING ligases is known to regulate the degradation of cytosolic misfolded proteins.We sought to investigate the role of CSN8/CSN in misfolded protein degradation and cardiac proteinopathy.Cardiac CSN8 knockout causes mouse premature death; hence, CSN8 hypomorphism (CSN8(hypo)) mice were used. Myocardial neddylated forms of cullins were markedly increased, and myocardial capacity of degrading a surrogate misfolded protein was significantly reduced by CSN8 hypomorphism. When introduced into proteinopathic mice in which a bona fide misfolded protein R120G missense mutation of αβ-crystallin (CryAB(R120G)) is overexpressed in the heart, CSN8 hypomorphism aggravated CryAB(R120G)-induced restrictive cardiomyopathy and shortened the lifespan of CryAB(R120G) mice, which was associated with augmented accumulation of protein aggregates, increased neddylated proteins, and reduced levels of total ubiquitinated proteins and LC3-II in the heart. In cultured cardiomyocytes, both CSN8 knockdown and cullin-RING ligase inactivation suppressed the ubiquitination and degradation of CryAB(R120G) but not native CryAB, resulting in accumulation of protein aggregates and exacerbation of CryAB(R120G) cytotoxicity.(1) CSN8/CSN promotes the ubiquitination and degradation of misfolded proteins and protects against cardiac proteotoxicity, and (2) cullin-RING ligases participate in degradation of cytosolic misfolded proteins.
Abstract P3-11-15: Different clinical usefulness of AJCC response criteria according to the subtypes in stage II/III breast cancer patients after neoadjuvant chemotherapy
Authors: Yaewon Yang, Seock-Ah Im, Tae-Yong Kim, Kyung-Hun Lee, Bhumsuk Keam, Sae-Won Han, Do-Youn Oh, Tae-You Kim, Wonshik Han, Hyeong-Gon Moon, In Ae Park, Dong-Young Noh
Journal: Cancer Research (2015)

Abstract Background: Response to neoadjuvant chemotherapy (NAC) is a useful prognostic marker for relapse and overall survival but their prognostic role is distinct in different breast cancer subtypes. Pathologic complete response (pCR) is a current gold standard for evaluating response to NAC. Despite its clinical usefulness, discrimination into pCR and non-pCR is too simple because non-pCR includes broad range of actual responses from very good partial response to even progressive disease. American Joint Committee on Cancer (AJCC) 7th edition proposed response criteria for NAC based on precise clinical stage before NAC and pathologic staging after NAC. The purpose of this study is to evaluate the clinical usefulness of AJCC response criteria in each breast cancer subtypes. Patients and Methods: Patients with clinical stage II or III breast cancer treated with NAC at Seoul National University Hospital were enrolled and reviewed retrospectively. AJCC response criteria for NAC were adopted from the AJCC 7th edition: complete response (CR), absence of invasive carcinoma in both breast and lymph node; partial response (PR), decrease in either or both T or N stage; no response (NR), no change or increase in either or both T or N stage. The definition of each breast cancer subtypes were adopted from 2011 St Gallen Consensus Panel for current study. Results: From January 2009 to December 2010, 183 patients were enrolled in the study with median follow up period of 38.0 months. AJCC response was significantly associated with relapse free survival (RFS) (P&amp;lt;0.001), whereas pCR was not (P=0.120). In subgroup analysis, AJCC response was a significant prognostic factor for RFS in luminal B (P&amp;lt;0.001), HER-2 enriched (P=0.035) and triple negative breast cancer (P=0.037) groups, but not in luminal A group patients (P=0.101). On the contrary, pCR was not significantly associated with RFS in any groups. Conclusion : AJCC criteria is an easily reproducible tool for response evaluation for breast cancer patients in NAC setting compared with classically used pCR in all breast cancer subgroups except luminal A. Citation Format: Yaewon Yang, Seock-Ah Im, Tae-Yong Kim, Kyung-Hun Lee, Bhumsuk Keam, Sae-Won Han, Do-Youn Oh, Tae-You Kim, Wonshik Han, Hyeong-Gon Moon, In Ae Park, Dong-Young Noh. Different clinical usefulness of AJCC response criteria according to the subtypes in stage II/III breast cancer patients after neoadjuvant chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-15.
A Transplantable Hamster Sarcoma Produced by Spontaneously Transformed Kidney Cell Line of Baby Hamster
Authors: Traykovich, Vera
Journal: JNCI Journal of the National Cancer Institute (1968)

Journal Article A Transplantable Hamster Sarcoma Produced by Spontaneously Transformed Kidney Cell Line of Baby Hamster Get access Vera Traykovich, M.D. Vera Traykovich, M.D. Institute Venezolano de Investigaciones Cientificas, Caracas, Venezuela Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 41, Issue 5, November 1968, Pages 1039–1050, https://doi.org/10.1093/jnci/41.5.1039 Published: 01 November 1968 Article history Received: 26 February 1968 Accepted: 10 July 1968 Published: 01 November 1968
Haematologists should be treat sickle cell disease
Authors: Piotr Szawarski
Journal: BMJ (2007)

Having worked in a UK haematology centre that cared for patients with sickle cell disease, I understand the case for dedicated sickle cell centres,1 but we should be wary of centralising services for these patients. Day centres are excellent, but during weekends or nights patients may find access difficult. Also, these patients may come under the care of non-haematology specialists in district general hospitals. The key to care for patients in these circumstances is active involvement from haematologists, who probably have the greatest understanding of the disorder. Just as intensive care has adopted the “without walls” approach with readily available outreach services, patients with sickle cell disease should receive expert haematology input on a daily basis wherever they are in the hospital. Support for non-haematology staff—including good communication and 24 hour availability of advice—would help them understand the problems and their management and increase their experience, confidence, and competence in looking after this challenging group of patients.
Response to: ‘In the idiopathic inflammatory myopathies, reactive oxygen species are at the crossroad between immune and non-immune cell mediated mechanisms’ by Meyer<i>et al</i>
Authors: Adam P Lightfoot, Robert G Cooper
Journal: Annals of the Rheumatic Diseases (2015)

Response to: 'In the idiopathic inflammatory myopathies, reactive oxygen species are at the crossroad between immune and non-immune cell mediated mechanisms' by Meyer et alWe welcome the comments from Meyer et al 1 regarding our recent article which hypothesised a potential role for reactive oxygen species (ROS) as a mediator of muscle weakness induction in the idiopathic inflammatory myopathies (IIM). 2 The focus of our article was specifically on the persistence of muscle weakness in the treated paucity or absence of inflammatory cell infiltrates, and the role that ROS may play as a mediator of this residual and non-inflammatory dysfunction. 2In our article we did not try to imply that the mechanisms of actions of immune cells and ROS generation are mutually exclusive, as clearly inflammatory cell infiltrations are a cause of muscle cell injury and thus weakness.In another recent, and related, review we suggest that inflammatory cell infiltration is in fact a 'secondary' feature in IIM. 3 We agree that there is likely an interaction between immune cell-mediated and ROS-mediated muscle dysfunction.The interesting beneficial effects of using ROS-targeted therapies as described by Meyer et al 4 in the context of IIM thus appear timely and indeed fundamentally important.Based on their findings and our own postulates, it is perhaps logical to now consider the role of ROS in immune and non-immune settings in IIM.Moreover, and given the recent advances in ROS-targeted compounds, a new dawn may now be on the horizon regarding novel therapeutics to target weakness in IIM.
Administration of an anti-interleukin-6 monoclonal antibody to patients with acquired immunodeficiency syndrome and lymphoma: effect on lymphoma growth and on B clinical symptoms
Authors: D Emilie, J Wijdenes, C Gisselbrecht, B Jarrousse, E Billaud, JY Blay, J Gabarre, JP Gaillard, J Brochier, M Raphael
Journal: Blood (1994)
A 7-Gene Microrna Signature Characteristic of Mantle Cell Lymphoma Reveals Focal Adhesion and Integrin Signalling, Proteasome-Mediated Degradation, and the PI3K Signalling Cascade As Important to MCL Pathogenesis
Authors: Rashmi S. Goswami, Yali Xuan, Levi Waldron, Mahadeo A. Sukhai, Patricia P Reis, Thomas Sun, Alessandro Datti, Wei Xu, John Kuruvilla, David Good, Raymond Lai, Wilson Lam, Alanna Church, David LeBrun, Laurie H. Sehn, Pedro Farinha, Igor Jurisica, Denis Bailey, Randy D. Gascoyne, Michael Crump, Suzanne Kamel-Reid
Journal: Blood (2012)
Association between Eye Shape and Myopic Traction Maculopathy in High Myopia
Authors: Tomotaka Wakazono, Kenji Yamashiro, Masahiro Miyake, Hideo Nakanishi, Akio Oishi, Sotaro Ooto, Akitaka Tsujikawa, Nagahisa Yoshimura
Journal: Ophthalmology (2015)
GW25-e0796 Attenuation of CLOCK-BMAL1 transcriptionally decreases the expression of β1-AR to anticipate the occurrence of ventricular arrhythmia after chronic heart failure
Authors: Yuan Jiamin, Zhiyong Qian, Peibing Ge, Yao Wang, Yanhong Chen, Xiaofeng Hou, Jiangang Zou
Journal: Journal of the American College of Cardiology (2014)
Assessment and management of facial nerve palsy
Authors: Liam Masterson, Martin Vallis, Ros Quinlivan, Peter Prinsley
Journal: BMJ (2015)

#### The bottom line

#### How patients were involved in the creation of this article

We sought feedback on the paper from patient and medical representatives of the charity Facial Palsy UK. We incorporated their comments into the paper and developed a patient consultation guide for management and prognosis of Bell’s palsy (see box below)

The facial nerve is important for both communication and expression, and impairment of its function can severely affect quality of life.1 The main concern at first presentation of a facial nerve lesion is to exclude the possibility of a stroke or other serious cause.2 The figure⇓ outlines possible causes. Correct management within the first few days may prevent long term complications.



Differential diagnosis of a unilateral facial palsy. Percentages are based on combined epidemiological data from 6024 patients with lower motor neurone facial palsy (rarer conditions including mumps, syphilis, HIV, Guillain-Barre syndrome, otitic barotrauma, myasthenia gravis, systemic lupus erythematosus, sarcoidosis, and multiple sclerosis have been excluded).3 4 *Endemic in forested regions; †misdiagnosed cerebrovascular disease evident in about 1.5% of all patients3



The facial nerve is responsible for motor supply to the muscles of facial expression (frontalis, orbicularis oculi, buccinators, and orbicularis oris) and stapedius, parasympathetic supply to the lacrimal and submandibular glands, …
Surgery, angioplasty, or medical therapy for symptomatic multivessel coronary artery disease
Authors: William E Boden
Journal: Journal of the American College of Cardiology (2004)

We all like to embrace winning strategies for patient management in cardiovascular therapeutics. These strategies are important because we are so often besieged with a spectrum of treatment options, and both patients and their families, as well as referring physicians, implicitly put their trust in
O033 : CCR2+ infiltrating monocytes promote acetaminophen-induced acute liver injury – therapeutic implications of inhibiting CCR2 and CCL2
Authors: O. Krenkel, J.C. Mossanen, C. Ergen, F. Heymann, E. Lefebvre, D. Eulberg, C. Trautwein, F. Tacke
Journal: Journal of Hepatology (2015)
The CD4+/CD8+ ratio as a prognostic factor in patients with metastatic melanoma receiving chemoimmunotherapy.
Authors: M Hernberg, T Muhonen, J P Turunen, M Hahka-Kemppinen, S Pyrhönen
Journal: Journal of Clinical Oncology (1996)

PURPOSE As reported earlier, a chemotherapy regimen that consisted of dacarbazine, vincristine, lomustine, and bleomycin (DOBC) combined with natural leukocyte interferon (IFN) has been administered with favorable results to patients with metastatic melanoma. In this study, lymphocyte subsets (CD4+ and CD8+) were analyzed before and during treatment to elucidate if alterations in the CD4+/CD8+ ratio had any prognostic value. MATERIALS AND METHODS Blood samples were systematically obtained from 54 patients with metastatic melanoma who received this chemoimmunotherapy. The frequencies of peripheral-blood lymphocyte subsets were monitored by flow cytometry using the monoclonal antibodies OKT4 (CD4+, T-helper cells) and OKT8 (CD8+, T-suppressor cells). RESULTS Twenty-seven patients had a constantly increasing ratio, while the remaining 27 patients had a fluctuating or constantly decreasing ratio. The former group had a median survival time of 11.8 months, as compared with 6.5 months for the latter (P = .008, log-rank test). This difference was generated among patients who had an objective response. Responding patients with a constantly increasing ratio had a median survival time of 21.7 months, as compared with 10.2 months for patients with no constant increase in the ratio (P = .038, log-rank test). In nonresponders, no difference in survival was observed between the two groups. CONCLUSION The monitoring of early changes in the CD4+/CD8+ ratio can provide valuable information that predicts the prognosis of metastatic melanoma patients receiving chemoimmunotherapy.
Letter by Broekman and van Dam Regarding Article, “Fat Embolism Syndrome”
Authors: Marike Broekman, Marjel van Dam
Journal: Circulation (2015)

We read with great interest the Clinician Update on fat embolism syndrome by Kosova et al 1 published in Circulation.The article gave a clear and concise overview.One important conclusion is that patients with central nervous system dysfunction resulting from fat embolism syndrome require frequent neurological examinations.In addition, the authors argue that intracranial pressure (ICP) monitoring should be considered, advice based on a case report/literature review by Kellogg et al 2 over several decades in which only 1 of 33 patients with fat embolism syndrome underwent ICP monitoring.We feel strongly that a single case report is not sufficient evidence to justify their recommendation to consider ICP monitoring.Especially because recent literature shows that ICP monitoring may not be beneficial for patients with traumatic brain injury, 3 the evidence for ICP monitoring in patients with nontraumatic brain injury is even more limited.
Endometriosis may be the pre-malignant lesion for certain histologic subtypes of ovarian cancers
Authors: A. Sultan, J. Killeen, O. Sultan, M. E. Carney
Journal: Journal of Clinical Oncology (2008)

16504 Background: The association of ovarian carcinoma and endometriosis has been suggested but there has been limited analysis of this relationship. Recent studies have shown only a 20–40% correlation of ovarian cancer with endometriosis. The objective of this study was to demonstrate the concurrent findings of endometriosis and ovarian cancer in our diverse population and to investigate if endometriosis is the pre-malignant lesion for certain ovarian cancer subtypes. Methods: Microscopic slides of primary epithelial ovarian cancers resected at the time of hysterectomy and salpingo-oopherectomy from 2000–2005 were reviewed for the presence of endometriosis. Their counterpart paraffin-embedded tissue samples were obtained and used for immunohistochemical staining of several candidate genes and their differential protein expression profiles were recorded. Results: While the overall incidence of epithelial ovarian cancers in Hawaii was comparable to other populations, the incidence of cancer subtypes differed. Serous, endometrioid, and clear cell cancers had similar incidence rates (28%, 29%, and 21% respectively) in our population compared to the general population where serous subtypes predominate (40–50%) and clear cell is found less often (10%). Unlike the general population, clear cell and endometrioid subtypes in our population were associated with endometriosis to a much greater extent (92% and 94%) - the highest correlation seen to date. Mucinous cancers were less commonly associated (67%), while serous carcinomas were rarely associated (6%). There also appeared to be a predilection for age <50 yo with the endometriosis-associated cancers. Finally, examination of different candidate genes revealed discrete expression patterns among the cancer subtypes, mimicked to a lesser extent in their coexisting endometriosis sites. Conclusions: This data represents the first time that endometriosis has been associated with clear cell and endometrioid subtypes to such a profound degree suggesting that endometriosis may indeed be the pre-malignant lesion of certain epithelial ovarian cancer subtypes. Further studies will be needed to elucidate this association fully and examine, if perhaps, ethnicity plays a larger role than previously thought. No significant financial relationships to disclose.
Renal Therapeutic Angiogenesis Using a Bioengineered Polymer-Stabilized Vascular Endothelial Growth Factor Construct
Authors: Alejandro R. Chade, Nathan A. Tullos, Taylor W. Harvey, Fakhri Mahdi, Gene L. Bidwell
Journal: Journal of the American Society of Nephrology (2015)

Renovascular disease (RVD) induces renal microvascular (MV) rarefaction that drives progressive kidney injury. In previous studies, we showed that renal vascular endothelial growth factor (VEGF) therapy attenuated MV damage, but did not resolve renal injury at practical clinical doses. To increase the bioavailability of VEGF, we developed a biopolymer-stabilized elastin-like polypeptide (ELP)-VEGF fusion protein and determined its in vivo potential for therapeutic renal angiogenesis in RVD using an established swine model of chronic RVD. We measured single-kidney blood flow (RBF) and GFR and established the degree of renal damage after 6 weeks of RVD. Pigs then received a single stenotic kidney infusion of ELP-VEGF (100 μ g/kg), a matching concentration of unconjugated VEGF (18.65 μ g/kg), ELP alone (100 μ g/kg), or placebo. Analysis of organ distribution showed high renal binding of ELP-VEGF 4 hours after stenotic kidney infusion. Therapeutic efficacy was determined 4 weeks after infusion. ELP-VEGF therapy improved renal protein expression attenuated in RVD, restoring expression levels of VEGF, VEGF receptor Flk-1, and downstream angiogenic mediators, including phosphorylated Akt and angiopoietin-1 and -2. This effect was accompanied by restored MV density, attenuated fibrogenic activity, and improvements in RBF and GFR greater than those observed with placebo, ELP alone, or unconjugated VEGF. In summary, we demonstrated the feasibility of a novel therapy to curtail renal injury. Recovery of the stenotic kidney in RVD after ELP-VEGF therapy may be driven by restoration of renal angiogenic signaling and attenuated fibrogenic activity, which ameliorates MV rarefaction and improves renal function.
Centrosomin represses dendrite branching by orienting microtubule nucleation
Authors: Cagri Yalgin, Saman Ebrahimi, Caroline Delandre, Li Foong Yoong, Saori Akimoto, Heidi Tran, Reiko Amikura, Rebecca Spokony, Benjamin Torben-Nielsen, Kevin P White, Adrian W Moore
Journal: Nature Neuroscience (2015)
Liver Metastases From Colorectal Cancer: The Turning Point
Authors: Bernard Nordlinger, Philippe Rougier
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.6.1442 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11896089 Liver Metastases From Colorectal Cancer: The Turning Point Bernard NordlingerxBernard NordlingerSearch for articles by this author , Philippe RougierxPhilippe RougierSearch for articles by this author Show More Hospital Ambroise Paré, University of Paris, Paris-Boulogne, France https://doi.org/10.1200/JCO.2002.20.6.1442 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
A prospective study on the incidence of delayed nausea and vomiting following administration of carboplatin containing regimens for treatment of cancer without prophylactic aprepitant
Authors: M. A. Waqar, P. Chitneni, K. Williams, B. W. Goodgame, F. Gao, R. Govindan, M. Q. Baggstrom
Journal: Journal of Clinical Oncology (2008)

20626 Background: Delayed nausea and vomiting following administration of carboplatin containing chemotherapy regimen remains a clinically significant problem for patients with cancer despite administration of standard antiemetic prophylaxis (a 5-HT3 antagonist & dexamethasone). Methods: We report here preliminary results of an ongoing prospective study to evaluate the incidence of delayed chemotherapy-induced nausea and vomiting (CINV) after the first cycle of treatment. Previously untreated patients with newly diagnosed cancer scheduled to receive carboplatin containing regimen (AUC 5 or above) (but no prophylactic aprepitant) are eligible to participate. Primary endpoint is the incidence of CINV after cycle 1 of chemotherapy. Secondary endpoints include the incidence of CINV after the third cycle & the gender differences in incidence of CINV. Patients completed the Functional Living Index Emesis (FLIE) questionnaires 24, 48, 72 and 96 hours after receiving chemotherapy. Telephone interviews were conducted 24–48 hours following chemotherapy to assess the severity & need for breakthrough medications for CINV. Results: The characteristics of 50 patients enrolled thus far: 54% male, mean age 63.2 years (range 42.2 - 79.6 years) and 86% diagnosed with lung cancer. Thirty six percent of patients reported moderate to severe CINV 72 hours after chemotherapy, with symptoms persisting as long as 96 hours in 33% of the patients after cycle 1. Women had only a slightly higher incidence of CINV (38%) than men (35%) at 72 hours following cycle 1, but a significantly higher incidence of emesis was seen in women (31%) compared to men (8%) (P=0.047) at 72 hours following cycle 3. Conclusions: Without prophylactic aprepitant administration, one third of cancer patients receiving carboplatin containing regimen had moderate to severe delayed CINV. Percentage of patients with delayed CINV 24 hrs 48 hrs 72 hrs 96 hrs Cycle 1 13.51% 24.32% 36.11% 33.34% Cycle 3 3.85% 21.74% 20.00% 23.08% No significant financial relationships to disclose.