tbuckley/cabot-search huggingface dataset:
Conditional inactivation of the mouse SBP2 gene to elucidate the function of selenoproteins in prostate cancer
Authors: Milind Suraokar, Michael Mills, Jeri Kim, Scott Lippman, David Menter
Journal: Cancer Research (2007)

3881  Selenium (Se) has been shown to effectively prevent prostate cancer in epidemiological, animal and human clinical studies. The protective effect of Selenium (Se) in prostate cancer could be due to the antioxidant function of the selenoproteins and/or the anti-tumorigenic effect of the Se metabolites. The phenotype of mice lacking selenoproteins, along with their response to Se supplementation regimen, will help to distinguish between the relative importances of these two factors in prostate cancer. Since the mammalian selenoproteome consists of multiple proteins with potential overlapping function, we are developing gene knockout and knockdown methods to eliminate key elements specifically involved in the translation of all selenoproteins that include a special tRNA - Sec-tRNASec and the SECIS-binding protein-2 (SBP2). Pre-natal lethality occurs in mouse embryos deficient for the Sec-tRNASec, which suggests that some of these selenoproteins are essential for normal development. Our own in vitro RNAi studies, using different anti-SBP2 shRNA constructs transfected into mouse NIH-3T3 and human 293 HEK cells have indicated that SBP2 protein is essentially required in these cells since its absence results in apoptosis. Therefore, we are interested in generating a targeted mouse model, using the traditional Cre-loxP strategy, to determine the effects of conditional loss of the SBP2 gene in the prostate gland, thus addressing the role of selenoproteins in prostate cancer. To accomplish this goal we will be generating 2 strains of mice - one carrying a floxed-SBP2 allele and the other carrying a prostate-specific inducible Cre. Crossing these 2 strains would enable tamoxifen-inducible and prostate tissue-specific loss of the floxed-SBP2 allele in targeted mice. The early steps in generating the floxed-SBP2 strain involved screening a mouse 129 BAC library to isolate BAC clones containing the entire mouse SBP2 gene and subsequently cloning about 8 kb of the the 59 end of the gene. We are currently generating a targeting vector, which includes loxP sites flanking the putative transcriptional start site and exons 1 and 2 of SBP2 gene. Thus on Cre-catalyzed recombination this region would be deleted and SBP2 gene would be functionally knocked out. We would then electroporate the construct into murine embryonic stem (ES) cells, select for targeted ES cells and inject into mouse blastocysts to generate the SBP2-floxed strain of mice. To generate the Cre strain we injected into the pronucleus of FVB mice a transgenic construct (aR2D3), which includes a tamoxifen-inducible Cre (Cre-ERT2) under the control of a prostate-specific promoter (ARR2PB) and a red fluorescent protein marker (DsRedT3). We have acquired at least 4 founder mice transgenic for the aR2D3 construct and have setup matings to identify the ones that have an expressible and transmissible form of the transgene.
Prognostic markers of taxan plus cisplatin in non-small cell lung cancer (nsclc)
Authors: ByoungYong Shim, Jinyoung Yoo, Chi Hong Kim, So Hyang Song, Myeong Im Ahn, Sung Whan Kim, Sangyoung Roh, Deog Gon Cho, Kyu Do Cho, Hoon-Kyo Kim
Journal: Cancer Research (2008)

2170  Background  Taxan plus cisplatin is most commonly used for the first line chemotherapy of NSCLC. Because of the complexity of the molecular biology of NSCLC, studies on the chemosensitivity of these drugs have not yet been successful in creating chemosensitive marker assessment, although p53, k-ras, Her2, bcl2, & Tau have been described as possible chemo-sensitivity markers of taxan. This study evaluated such immunophenotypes and gene amplification to determine their significance for pt outcome. We will find the biological prognostic markers that can be easily applied in clinical practice of first line NSCLC chemotherapy.  Method  We reviewed the charts, radiographic findings & pathologic slides of the 35 pts who were enrolled in four clinical trials at St. Vincent’s Hospital from 2002 to 2007. Immunohistochemistry was performed using formalin-fixed, paraffin-embedded tissue samples to examine the expressions of p53, k-ras, Her2, bcl2, & Tau proteins. Chromogenic in situ hybridization (CISH) was also performed using same samples for the gene amplification of Her2. We studied the association between the expressions of these proteins and amplification of Her2 gene, and prognostic factors including response to chemotherapy & survival.  Results  The median age of the pts was 61 years (range 2-86 years) and there were 23 males & 12 females. Twenty-three pts were treated by paclitaxel+cisplatin, whereas 12 pts were treated by docetaxel+cisplatin. There were 19 adenocarcinomas, 13 squamous cell carcinomas, & 3 large cell carcinomas. Twenty-two pts (62.9%) achieved a partial response (PR), seven pts (20%) had a stable disease (SD), and six pts (17.1%) showed progressive disease (PD). No significant correlation was observed between the protein expression of p53, k-ras, Her2, bcl2, & Tau and tumor response. However, the CISH of Her2 revealed correlation with tumor response(p=0.018): 13 negatives vs 9 positives in pts with PR, 5 negatives vs 2 positives in SD, but all 6 pts were positive in PD. Furthermore, Her2 gene amplification was strongly associated with overall survival: 20.4 months (95% CI 7.9 to 32 months) in pts with CISH of Her2 negative group vs 9 months (95% CI 7.1 to 10 months) in pts with CISH of Her2 positive group(p=0.005). The immunohistochemical expression of p53, k-ras, Her2, bcl2, Tau proteins demonstrated no significant difference on survival. A multivariate analysis with Cox regression confirmed that CISH of Her2 was an the most significant independent prognostic factor with a risk ratio of 3.06(p = 0.009).  Conclusion  The Her 2 gene amplification was correlated with tumor response of taxan plus cisplatin and overall survival. Molecular analysis of Her 2 particularly, gene amplification, may provide assistance in the determination of tumor response to taxan plus cisplatin chemotherapy and prognosis in pts with NSCLC.
Time for a New Image of Parkinson Disease
Authors: Melissa J. Armstrong, Michael S. Okun
Journal: JAMA Neurology (2020)

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
Deubiquitinase USP7-mediated MCL-1 up-regulation enhances Arsenic and Benzo(a)pyrene co-exposure-induced Cancer Stem Cell-like property and Tumorigenesis
Authors: Ping Yang, Jie Xie, Yunfei Li, Hsuan-Pei Lin, William Fenske, Marco Clementino, Yiguo Jiang, Chengfeng Yang, Zhishan Wang
Journal: Theranostics (2020)

MCL-1 is up-regulated in cancer and a target for cancer treatment. How MCL-1 is up-regulated and whether MCL-1 up-regulation plays a role in tumorigenic process is not well-known. Arsenic and benzo(a)pyrene (BaP) are well-recognized lung carcinogens and we recently reported that arsenic and BaP co-exposure acts synergistically in inducing cancer stem cell (CSC)-like property and lung tumorigenesis. This study was performed to further investigate the underlying mechanism focusing on the role of MCL-1.
Exploring the Prognostic Role of Ki67 Proliferative Index in Merkel Cell Carcinoma of the Skin: Clinico-Pathologic Analysis of 84 Cases and Review of the Literature
Authors: Stefano La Rosa, Matteo Bonzini, Amedeo Sciarra, Sofia Asioli, Roberta Maragliano, Martina Arrigo, Maria Pia Foschini, Alberto Righi, Francesca Maletta, Alberico Motolese, Mauro Papotti, Fausto Sessa, Silvia Uccella
Journal: Endocrine Pathology (2020)

Abstract The exact prediction of outcome of patients with Merkel cell carcinoma (MCC) of the skin is difficult to determine, although several attempts have been made to identify clinico-pathologic prognostic factors. The Ki67 proliferative index is a well-known marker routinely used to define the prognosis of patients with neuroendocrine neoplasms. However, its prognostic value has been poorly investigated in MCC, and available published results are often contradictory mainly because restricted to small series in the absence of standardized methods for Ki67 evaluation. For this reason, we explored the potential prognostic role of Ki67 proliferative index in a large series of MCCs using the WHO standardized method of counting positive cells in at least 500 tumor cells in hot spot areas on camera-captured printed images. In addition, since MCC may be considered as the cutaneous counterpart of digestive neuroendocrine carcinomas (NECs), we decided to stratify MCCs using the available and efficient Ki67 threshold of 55%, which was found prognostic in digestive NECs. This choice was also supported by the Youden index analysis. In addition, we analyzed the prognostic value of other clinico-pathologic parameters using both univariate and multivariate analysis. Ki67 index appeared significantly associated with prognosis at univariate analysis together with stage IV, lack of MCPyV, and p63 expression, but not at the multivariate analysis, where survival resulted independently influenced by p63 expression and tumor stage, only.
Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis
Authors: Anquan Shang, Chenzheng Gu, Weiwei Wang, Xuan Wang, Junjun Sun, Bingjie Zeng, Chen Chen, Wenjing Chang, Yili Ping, Ping Ji, Junlu Wu, Wenqiang Quan, Yiwen Yao, Yongxin Zhou, Zujun Sun, Dong Li
Journal: Molecular Cancer (2020)

Abstract Background Colorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators of intercellular communication and that abundant Circular RNAs (circRNAs) are enriched within exosomes. CircRNAs are novel members of noncoding RNAs regulating cancer proliferation and progression. However, the function and regulatory mechanism of cancer-derived exosomal circRNAs in CRC remains unclear. Methods CRC cells-derived exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blot. CCK-8, wound healing and transwell assays, and flow cytometry assays were conducted to assess whether exosomes would affect the proliferation, metastasis, and apoptosis of CRC cells, respectively. Moreover, we performed the RNA sequencing and RT-qPCR to identify circRNAs in exosome-stimulated CRC cells. Fluorescence in situ hybridization (FISH) assay was used to detect the cellular distribution of circPACRGL. Bioinformatic analyses (StarBase 2.0) were used to pool the miRNA targets of circPACRGL. Luciferase assays were performed to verify the direct interaction. Finally, flow cytometry was used to detect the differentiation of N1-N2 neutrophils. Results Our study identified a novel CRC-derived exosomal circRNA, circPACRGL. We found circPACRGL was significantly upregulated in CRC cells after tumor-derived exosomes addition . Moreover, circPACRGL serves as a sponge for miR-142-3p/miR-506-3p to facilitate the transforming growth factor- β1 (TGF-β1) expression. As a result, circPACRGL promoted CRC cell proliferation, migration and invasion, as well as differentiation of N1 to N2 neutrophils via miR-142-3p/miR-506-3p-TGF- β1 axis. Conclusion Our study, the first to reveal that cancer-derived exosomal circPACRGL plays an oncogenic role in CRC proliferation and metastasis, providing mechanistic insights into the roles of circRNAs in CRC progression and a valuable marker for CRC treatment.
Medications for Primary Prevention of Breast Cancer
Authors: Yiwey Shieh, Jeffrey A. Tice
Journal: JAMA (2020)

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
Talin1 sets the stage for dendritic cell activation
Authors: Björn E. Clausen
Journal: The Journal of Experimental Medicine (2020)

In this issue of JEM, Lim et al. (https://doi.org/10.1084/jem.20191810) provide exciting new evidence that talin1 plays an essential role in dendritic cell (DC) maturation and activation. Using conditional knockout mice, they demonstrate that talin1 promotes the formation of a preassembled TLR–Myddosome signaling complex in steady-state DCs but not macrophages. This may explain why DCs respond faster and more vigorously to TLR ligand binding than their closely related macrophages.
Salvage endoscopic ultrasound-guided rendezvous technique for disconnected pancreatic duct syndrome in a patient with severe acute pancreatitis
Authors: Shinichi Hashimoto, Hiromichi Iwaya, Shiroh Tanoue, Yusuke Fujino, Makoto Hinokuchi, Shiho Arima, Akio Ido
Journal: Endoscopy (2020)

Disconnected pancreatic duct syndrome (DPDS) is characterized by extraductal leakage of pancreatic juice and destruction of tissue surrounding the pancreas [1]. Many DPDS cases need surgical treatment [2]. Transpapillary pancreatic stenting and endoscopic ultrasound (EUS)-guided transmural drainage of PD and walled-off necrosis (WON) are also reported to be effective for DPDS [2] [3] [4]. The EUS-guided rendezvous technique (EUS-RV) was shown to be effective as a salvage procedure to connect to the disruption directly when drainage procedures to treat DPDS proved ineffective.
Three-dimensional bioprinted hepatorganoids in liver failure
Authors: Savneet Kaur, Dinesh Mani Tripathi, Sourabh Ghosh
Journal: Gut (2020)

We read with interest the recent study by Yang et al , who reported the construction of three-dimensional bioprinted hepatorganoids (3DP-HOs) using HepaRG cells and bioinks.1 We congratulate the authors for this pioneering study that demonstrates the fabrication and in vivo application of functional 3DP-HOs in mice models of liver failure. The study would pave the way for the use of three-dimensional (3D) bioprinted primary hepatocytes and/or hepatic progenitor cells as possible regenerative therapies in liver diseases. However, there are some caveats in the study, which need to be highlighted.

First, the study showed that after 7 days of differentiation in vitro, HepaRG cells in 3DP-HOs expressed hepatic marker genes and exhibited albumin secretion (figure 2). However, it is to be noted that most of …
Morphological transformation enhances Tumor Retention by Regulating the Self-assembly of Doxorubicin-peptide Conjugates
Authors: Liu Xu, Yutong Wang, Chenqi Zhu, Shujing Ren, Yurou Shao, Li Wu, Weidong Li, Xiaobin Jia, Rongfeng Hu, Rui Chen, Zhipeng Chen
Journal: Theranostics (2020)

Both spatial accuracy and temporal persistence are crucial in drug delivery, especially for anti-tumor intravenous nanomedicines, which have limited persistence due to their small particle sizes and easy removal from tumors. The present study takes advantage of morphological transformation strategy to regulate intravenous nanomedicines to display different sizes in different areas, achieving high efficient enrichment and long retention in lesions.
AB0613 AUTONOMIC NEUROPATHY AND ITS PREDICTORS IN SYSTEMIC SCLEROSIS
Authors: A. Syngle, N. Garg, D. Gera
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic sclerosis (SSc), a chronic autoimmune disease, is associated with autonomic neuropathy 1 . Autonomic neuropathy, especially cardiovascular autonomic neuropathy (CAN) is significant risk predictor of sudden cardiac death. However, its relationship with disease specific measures remains unexplored in SSc. Objectives: To assess cardiovascular autonomic neuropathy and sudomotor function and its predictors in systemic sclerosis. Methods: In this cross-sectional study, 16 SSc patients meeting the 2013 European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) classification criteria and 15 age and sex-matched healthy controls were recruited. Cardiovascular autonomic function assessed by five cardiovascular reflex tests according to Ewing. Peripheral sympathetic autonomic function assessed by FDA approved Sudoscan (Impeto Medical, Paris) through measurement of electrochemical skin conductance. Disease-specific measures (Disease duration, Modified Rodnan Skin Score (mRSS), EUSTAR activity score), and inflammatory measures (ESR, CRP) were determined. Quality of life measured by Scleroderma Health Assessment Questionnaire (SHAQ). Results: Systemic sclerosis patients had significantly impaired parasympathetic [Heart rate response to deep breath (HRD) (Fig. 1A), Heart rate response to standing (HRS) (Fig. 1B) and Heart rate response to valsalva manoeuvre (Fig. 1C)] and symapathetic [BP response to hand grip (BPH) (Fig. 1D)] function as compared to healthy controls. Scleroderma patients had significantly impaired sudomotor function (p&lt;0.05) as compared to healthy controls. Levels of mRSS, EUSTAR score, ESR, CRP and SHAQ were significantly higher in SSc patients as compared to healthy controls (p≤0.05). Parasympathetic (HRD &amp; HRS) dysfunction inversely correlated with ESR, CRP and mRSS. Sudomotor function positively correlated with mRSS, disease duration and CRP. Conclusion: CAN and Sudomotor function are significantly impaired in SSc. Parasympathetic dysfunction is more pronounced than sympathetic dysfunction in SSc. CAN and Sudomotor dysfunction are associated with disease-duration, skin-score, ESR and CRP. These could serve as potential predictors of Cardiovascular Autonomic neuropathy and sudomotor dysfunction in SSc. References: [1]Dessein PH, Joffe BI, Metz RM, Millar DL, Lawson M, Stanwix AE. Autonomic dysfunction in systemic sclerosis: sympathetic overactivity and instability. The American journal of medicine. 1992;93(2):143-50. Acknowledgments: None Disclosure of Interests: None declared
Abnormal carbon monoxide diffusion capacity in COVID-19 patients at time of hospital discharge
Authors: Samir Nusair
Journal: European Respiratory Journal (2020)

<b>On recovery from COVID-19 it is important to draw attention to the CO diffusion test and the actual meaning of the findings when considering the values of <i>D</i><sub>LCO</sub> and <i>D</i><sub>LCO</sub>/<i>V</i><sub>A</sub> put together</b>https://bit.ly/36k2O2Q
Evaluation of Risk of Bullous Pemphigoid With Initiation of Dipeptidyl Peptidase–4 Inhibitor vs Second-generation Sulfonylurea
Authors: Hemin Lee, Hye Jin Chung, Ajinkya Pawar, Elisabetta Patorno, Dae Hyun Kim
Journal: JAMA Dermatology (2020)

Despite several recent reports on the elevated risk of bullous pemphigoid in patients with type 2 diabetes treated with dipeptidyl peptidase-4 (DPP-4) inhibitors, evidence on the absolute risk and comparative safety against other antidiabetics is limited.To characterize the incidence rate of bullous pemphigoid associated with DPP-4 inhibitor use compared with second-generation sulfonylureas.This cohort study used data from 2 large commercial insurance claims databases (Optum Clinformatics Data Mart from October 17, 2006, to December 31, 2018, and IBM MarketScan Research Database from October 17, 2006, to December 31, 2017) and Medicare data from January 1, 2006, to December 31, 2016. Patients with type 2 diabetes who initiated treatment with DPP-4 inhibitors or second-generation sulfonylurea were included.The primary outcome of the study was bullous pemphigoid, identified using diagnosis codes. After 1:1 propensity score matching, the incidence rates of bullous pemphigoid and the hazard ratios (HRs) with 95% CIs comparing patients who initiated DPP-4 inhibitor and second-generation sulfonylurea therapy were estimated. Subgroup analyses by age, sex, race, and individual DPP-4 agents were performed. The results from each database were pooled using inverse-variance fixed-effects meta-analysis.A total of 1 664 880 patients who initiated DPP-4 inhibitors (51.0% female; mean [SD] age, 63.9 [9.7] years) and sulfonylurea (50.4% female; mean [SD] age, 63.9 [9.9] years) were included. The incidence rate of bullous pemphigoid per 1000 person-years was 0.42 in the DPP-4 inhibitor group vs 0.31 in the sulfonylurea group (HR, 1.42; 95% CI, 1.17-1.72). Higher rates per 1000 person-years for DPP-4 inhibitor vs sulfonylurea groups were seen in those who were 65 years or older (0.79 vs 0.49; HR, 1.62; 95% CI, 1.32-1.99), white (0.93 vs 0.54; HR, 1.70; 95% CI, 1.30-2.24), and treated with linagliptin (1.20 vs 0.55; HR, 1.68; 95% CI, 1.16-2.43).This study found that patients who initiated DPP-4 inhibitor therapy had higher risk of bullous pemphigoid than those who initiated second-generation sulfonylurea therapy. Clinicians should be aware of this rare adverse effect of DPP-4 inhibitors in subgroups of patients who are older, white, and linagliptin users.
bmjlearning.com: None of the above?
Authors: Kieran Walsh
Journal: BMJ (2004)

Which of the following cities are furthest from London?

A: Plymouth

B: Cardiff

C: York

D: Paris

E: None of the above. 

“None of the above” often puzzles doctors when answering multiple choice questions.1 It can work if all the other options are clearly incorrect: it is then the only correct answer. However, it causes confusion when the options are not absolutely true or false. You then have to weigh in your mind whether one of the specific options is more correct than the infinite number of other options that are encapsulated in “None of the above.”1 Sometimes, as in the above question, it makes no sense at all.

BMJ Learning's online learning resources can help you with your appraisal and revalidation. We ask questions throughout the modules, but we avoid imprecise and ambiguous questions. Our new learning module on influenza outlines how to diagnose and treat patients with this condition. It also brings you up to date with recent advances such as the role of neuraminidase inhibitors and amantadine in treatment. It states the circumstances in which patients should receive these drugs for treatment and for post-exposure prophylaxis.

To find out more, go to our website, bmjlearning.com.