tbuckley/cabot-search huggingface dataset:
Epirubicin-loaded polymeric micelles effectively treat axillary lymph nodes metastasis of breast cancer through selective accumulation and pH-triggered drug release
Authors: Tsukasa Chida, Yutaka Miura, Horacio Cabral, Takahiro Nomoto, Kazunori Kataoka, Nobuhiro Nishiyama
Journal: Journal of Controlled Release (2018)

Suppression of axillary lymph node metastasis (ALNM) is an important goal in the treatment of breast cancer. While several therapies directed to ALNM have been evaluated, effective and safe treatments for ALNM in triple negative breast cancer (TNBC) have not been established yet, especially against initial/small metastases. Here, we demonstrated the therapeutic effect of an anthracycline drug, epirubicin (EPI)-loaded polymeric micelles equipped with pH-triggered drug release property (EPI/m) against ALNM of TNBC. EPI/m effectively inhibited the spread of the primary tumor and the growth of ALNM, through selective accumulation and penetration in both primary tumor and vascularized ALNM, as well as efficient drug activation triggered by the intratumoral acidic environment. Furthermore, we revealed that the improvement of the activated drug distribution of EPI/m contributed to dose-dependent enhancement of the antitumor effect through expansion of the therapeutic window. These findings highlight the utility of pH-responsive property in EPI/m for the treatment of ALNM in TNBC.
A Bioprinted Cardiac Patch Composed of Cardiac‐Specific Extracellular Matrix and Progenitor Cells for Heart Repair
Authors: Donald Bejleri, Benjamin W. Streeter, Aline L. Y. Nachlas, Milton E. Brown, Roberto Gaetani, Karen L. Christman, Michael E. Davis
Journal: Advanced Healthcare Materials (2018)

Abstract Congenital heart defects are present in 8 of 1000 newborns and palliative surgical therapy has increased survival. Despite improved outcomes, many children develop reduced cardiac function and heart failure requiring transplantation. Human cardiac progenitor cell (hCPC) therapy has potential to repair the pediatric myocardium through release of reparative factors, but therapy suffers from limited hCPC retention and functionality. Decellularized cardiac extracellular matrix hydrogel (cECM) improves heart function in animals, and human trials are ongoing. In the present study, a 3D‐bioprinted patch containing cECM for delivery of pediatric hCPCs is developed. Cardiac patches are printed with bioinks composed of cECM, hCPCs, and gelatin methacrylate (GelMA). GelMA‐cECM bioinks print uniformly with a homogeneous distribution of cECM and hCPCs. hCPCs maintain &gt;75% viability and incorporation of cECM within patches results in a 30‐fold increase in cardiogenic gene expression of hCPCs compared to hCPCs grown in pure GelMA patches. Conditioned media from GelMA‐cECM patches show increased angiogenic potential (&gt;2‐fold) over GelMA alone, as seen by improved endothelial cell tube formation. Finally, patches are retained on rat hearts and show vascularization over 14 d in vivo. This work shows the successful bioprinting and implementation of cECM‐hCPC patches for potential use in repairing damaged myocardium.
Adipokines Deregulate Cellular Communication via Epigenetic Repression of <i>Gap Junction</i> Loci in Obese Endometrial Cancer
Authors: Srikanth R. Polusani, Yi-Wen Huang, Guangcun Huang, Chun-Wei Chen, Chiou-Miin Wang, Li-Ling Lin, Pawel Osmulski, Nicholas D. Lucio, Lu Liu, Ya-Ting Hsu, Yufan Zhou, Chun-Lin Lin, Irene Aguilera-Barrantes, Philip T. Valente, Edward R. Kost, Chun-Liang Chen, Eun Yong Shim, Sang Eun Lee, Jianhua Ruan, Maria E. Gaczynska, Pearlly Yan, Paul J. Goodfellow, David G. Mutch, Victor X. Jin, Bruce J. Nicholson, Tim H.-M. Huang, Nameer B. Kirma
Journal: Cancer Research (2018)

Emerging evidence indicates that adipose stromal cells (ASC) are recruited to enhance cancer development. In this study, we examined the role these adipocyte progenitors play relating to intercellular communication in obesity-associated endometrial cancer. This is particularly relevant given that gap junctions have been implicated in tumor suppression. Examining the effects of ASCs on the transcriptome of endometrial epithelial cells (EEC) in an
Time to Colonoscopy and Risk of Colorectal Cancer in Patients With Positive Results From Fecal Immunochemical Tests
Authors: Yi-Chia Lee, Jean Ching-Yuan Fann, Tsung-Hsien Chiang, Shu-Lin Chuang, Sam Li-Sheng Chen, Han-Mo Chiu, Amy Ming-Fang Yen, Sherry Yueh-Hsia Chiu, Chen-Yang Hsu, Wen-Feng Hsu, Ming-Shiang Wu, Hsiu-Hsi Chen
Journal: Clinical Gastroenterology and Hepatology (2018)

<h3>Background & Aims</h3> In patients with positive results from a fecal immunochemical test (FIT), failure to receive a timely follow-up colonoscopy may be associated with higher risks of colorectal cancer (CRC) and advanced-stage CRC. We evaluated the prevalence of any CRC and advanced-stage CRC associated with delays in follow-up colonoscopies for patients with positive results from a FIT. <h3>Methods</h3> We collected data from 39,346 patients (age, 50–69 years) who participated in the Taiwanese Nationwide Screening Program from 2004 through 2012 and had completed a colonoscopy more than 1 month after a positive result from a FIT. Risks of any CRC and advanced-stage CRC (stage III-IV) were evaluated using logistic regression models and results expressed as adjusted odds ratios (aORs) and corresponding 95% CIs. <h3>Results</h3> In our cohort, 2003 patients received a diagnosis of any CRC and 445 patients were found to have advanced-stage disease. Compared with colonoscopy within 1–3 months (cases per 1000 patients: 50 for any CRC and 11 for advanced-stage disease), risks were significantly higher when colonoscopy was delayed by more than 6 months for any CRC (aOR, 1.31; 95% CI, 1.04–1.64; 68 cases per 1000 patients) and advanced-stage disease (aOR, 2.09; 95% CI, 1.43–3.06; 24 cases per 1000 patients). The risks continuously increased when colonoscopy was delayed by more than 12 months for any CRC (aOR, 2.17; 95% CI, 1.44–3.26; 98 cases per 1000 patients) and advanced-stage disease (aOR, 2.84; 95% CI, 1.43–5.64; 31 cases per 1000 patients). There were no significant differences for colonoscopy follow up at 3–6 months for risk of any CRC (aOR, 0.98; 95% CI, 0.86–1.12; 49 cases per 1000 patients) or advanced-stage disease (aOR, 0.95; 95% CI, 0.72–1.25; 10 cases per 1000 patients). <h3>Conclusions</h3> In an analysis of data from the Taiwanese Nationwide Screening Program, we found that among patients with positive results from a FIT, risks of CRC and advanced-stage disease increase with time. These findings indicate the importance of timely colonoscopy after a positive result from a FIT.
JCARH125, Anti-BCMA CAR T-cell Therapy for Relapsed/Refractory Multiple Myeloma: Initial Proof of Concept Results from a Phase 1/2 Multicenter Study (EVOLVE)
Authors: Sham Mailankody, Myo Htut, Kelvin P. Lee, William Bensinger, Todd Devries, Julia Piasecki, Safiyyah Ziyad, Michelle Blake, John Byon, Andrzej Jakubowiak
Journal: Blood (2018)
Ibrutinib Therapy Releases Leukemic Surface IgM from Antigen Drive in Chronic Lymphocytic Leukemia Patients
Authors: Samantha Drennan, Giorgia Chiodin, Annalisa D'Avola, Ian Tracy, Peter W. Johnson, Livio Trentin, Andrew J. Steele, Graham Packham, Freda K. Stevenson, Francesco Forconi
Journal: Clinical Cancer Research (2018)

Abstract Purpose: In chronic lymphocytic leukemia (CLL), disease progression associates with surface IgM (sIgM) levels and signaling capacity. These are variably downmodulated in vivo and recover in vitro, suggesting a reversible influence of tissue-located antigen. Therapeutic targeting of sIgM function via ibrutinib, an inhibitor of Bruton tyrosine kinase (BTK), causes inhibition and tumor cell redistribution into the blood, with significant clinical benefit. Circulating CLL cells persist in an inhibited state, offering a tool to investigate the effects of drug on BTK-inhibited sIgM. Experimental Design: We investigated the consequences of ibrutinib therapy on levels and function of sIgM in circulating leukemic cells of patients with CLL. Results: At week 1, there was a significant increase of sIgM expression (64% increase from pretherapy) on CLL cells either recently released from tissue or persisting in blood. In contrast, surface IgD (sIgD) and a range of other receptors did not change. SIgM levels remained higher than pretherapy in the following 3 months despite gradual cell size reduction and ongoing autophagy and apoptotic activity. Conversely, IgD and other receptors did not increase and gradually declined. Recovered sIgM was fully N-glycosylated, another feature of escape from antigen, and expression did not increase further during culture in vitro. The sIgM was fully capable of mediating phosphorylation of SYK, which lies upstream of BTK in the B-cell receptor pathway. Conclusions: This specific IgM increase in patients underpins the key role of tissue-based engagement with antigen in CLL, confirms the inhibitory action of ibrutinib, and reveals dynamic adaptability of CLL cells to precision monotherapy. See related commentary by Burger, p. 2372
Famitinib in combination with concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 1, open‐label, dose‐escalation Study
Authors: Qiuyan Chen, Linquan Tang, Na Liu, Feng Han, Ling Guo, Shanshan Guo, Jianwei Wang, Huai Liu, Yanfang Ye, Lu Zhang, Liting Liu, Pan Wang, Yingqin Li, Qingmei He, Xiaoqun Yang, Qingnan Tang, Yang Li, YuJing Liang, XueSong Sun, Chuanmiao Xie, Yunxian Mo, Ying Guo, Rui Sun, Haoyuan Mo, Kajia Cao, Xiang Guo, Musheng Zeng, Haiqiang Mai, Jun Ma
Journal: Cancer Communications (2018)

Abstract Background Famitinib is a tyrosine kinase inhibitor against multiple targets, including vascular endothelial growth factor receptor 2/3, platelet‐derived growth factor receptor, and stem cell factor receptor (c‐kit). Previous studies have demonstrated anti‐tumour activities of famitinib against a wide variety of advanced‐stage solid cancers. We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We also evaluated the feasibility of contrast‐enhanced ultrasound (D‐CEUS) as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy. Methods The trial was conducted in subjects with stage III or IVa‐b NPC using a 3 + 3 design of escalating famitinib doses. Briefly, subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT. D‐CEUS of the neck lymph nodes was performed at day 0, 8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy. End points included safety, tolerability and anti‐tumour activity. Results Twenty patients were enrolled (six each for 12.5, 16.5 and 20 mg and two for 25 mg). Two patients in the 25 mg cohort developed dose‐limiting toxicities, including grade 4 thrombocytopenia and grade 3 hypertension. The most common grade 3/4 adverse events were leukopenia, neutropenia and radiation mucositis. D‐CEUS tests showed that more than 60% of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone, and the parameter response was associated with disease improvement. In the famitinib monotherapy stage, three patients (15%) showed partial responses. The complete response rate was 65% at the completion of treatment and 95% 3 months after the treatment ended. After a median follow‐up of 44 months, the 3‐year progression‐free survival (PFS) and distant metastasis‐free survival were 70% and 75%, respectively. Subjects with a decrease of perfusion parameter response, such as peak intensity decreased at least 30% after 1 week of famitinib treatment, had higher 3‐year PFS (90.9% vs. 44.4%, 95% CI 73.7%–100% vs. 11.9%–76.9%, P &lt; 0.001) than those with an increase or a reduction of less than 30%. Conclusions The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC. D‐CEUS is a reliable and early measure of efficacy for famitinib therapies. Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.
Addressing Risky Health Behaviors Among Vulnerable Youth Through the School Environment
Authors: Kendra S. Liljenquist, Tumaini R. Coker
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics 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 Pediatrics journal
Induction of dominant-negative BRG1 abolishes expression of CD44 protein via post-transcriptional mechanism in mouse NIH/3T3 cells.
Authors: Mehmet Karaca, Bernard E. Weissman
Journal: Cancer Research (2006)

5063  BRG1, the ATPase unit of a SWI/SNF chromatin remodeling complex, is involved in regulating a number of genes including CD44, a transmembrane glycoprotein. Altered expression of CD44 has been implicated in the progression of a vast array of cancers. A previous report indicated that BRG1 deficient cells had abrogated CD44 expression (Strobeck et al., 2001; Reisman et al., 2002). Because the mechanism for this loss remains unresolved, we hypothesized that BRG1 loss promotes methylation of the CD44 promoter. We have tested this notion using a Tet-Vp16 system to transactivate an enzymatically inactive from of BRG1 (dominant negative:dnBRG1) lacking ATPase activity. Immunofluorescence and real-time PCR (QT-PCR) assays were used to determine the expression of CD44 and BRG1. Furthermore, bisulfite sequencing was used to determine whether loss of CD44 expression is due to the hypermethylation of the promoter region of CD44. Our results show that cells lost CD44 expression 1-3 passages after induction of dnBRG1 by immunofluorescence. However, CD44 levels returned to normal by 6 passages after transactivation of the dnBRG1. The result of the RNA expression analysis of CD44 by QT-PCR indicated no difference in expression between cells that express wild type BRG1 versus dnBRG1. By QT-PCR ChIPs analysis, we did not find the flag-tagged dnBRG-1 at the CD44 promoter. Therefore, our preliminary ChIPs data correlate with the expression data. Bisulfite sequencing demonstrated that the promoter region of CD44 showed few changes in DNA methylation. However, we cannot rule out the possibility that BRG1 and/or BRM loss by other mechanisms may influence cellular DNA methylation patterns. Our results suggest that the dnBRG1 may disrupt CD44 expression via a post-transcriptional mechanism. These studies show the caveat of using dominant-negative approaches to study regulation of transcription. Reisman, D. N., M. W. Strobeck, B. L. Betz, J. Sciariotta, W. Funkhouser, Jr., C. Murchardt, M. Yaniv, L. S. Sherman, E. S. Knudsen, and B. E. Weissman. 2002. Concominant down-regulation of BRM and BRG1 in human tumor cell lines: differential effects on RB-mediated growth arrest vs CD44 expression. Oncogene 21:1196-207. Strobeck, M. W., M. F. DeCristofaro, F. Banine, B. E. Weissman, L. S. Sherman, and E. S. Knudsen. 2001. The BRG-1 subunit of the SWI/SNF complex regulates CD44 expression. J. Biol. Chem. 276:9273-8.
Quality and Safety in Health Care, Part XLVIII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2018)

Discussion groups are one of the methods advocated to help prevent burnout and help in recovery from burnout. Balint groups, Schwartz Rounds, narrative medicine and reflection groups, discussion workshops to gain certain skills, and general support groups are examples of these groups. Participation in these groups produces other positive ramifications for health care providers and health care systems including promoting teamwork, collegiality, support networking, decreasing stress, and finding meaning in work.
Genetic Variants of <i>VEGFA</i> and <i>FLT4</i> Are Determinants of Survival in Renal Cell Carcinoma Patients Treated with Sorafenib
Authors: Daniel J. Crona, Andrew D. Skol, Veli-Matti Leppänen, Dylan M. Glubb, Amy S. Etheridge, Eleanor Hilliard, Carol E. Peña, Yuri K. Peterson, Nancy Klauber-DeMore, Kari K. Alitalo, Federico Innocenti
Journal: Cancer Research (2018)

Abstract Molecular markers of sorafenib efficacy in patients with metastatic renal cell carcinoma (mRCC) are not available. The purpose of this study was to discover genetic markers of survival in patients with mRCC treated with sorafenib. Germline variants from 56 genes were genotyped in 295 patients with mRCC. Variant-overall survival (OS) associations were tested in multivariate regression models. Mechanistic studies were conducted to validate clinical associations. VEGFA rs1885657, ITGAV rs3816375, and WWOX rs8047917 (sorafenib arm), and FLT4 rs307826 and VEGFA rs3024987 (sorafenib and placebo arms combined) were associated with shorter OS. FLT4 rs307826 increased VEGFR-3 phosphorylation, membrane trafficking, and receptor activation. VEGFA rs1885657 and rs58159269 increased transcriptional activity of the constructs containing these variants in endothelial and RCC cell lines, and VEGFA rs58159269 increased endothelial cell proliferation and tube formation. FLT4 rs307826 and VEGFA rs58159269 led to reduced sorafenib cytotoxicity. Genetic variation in VEGFA and FLT4 could affect survival in sorafenib-treated patients with mRCC. These markers should be examined in additional malignancies treated with sorafenib and in other angiogenesis inhibitors used in mRCC. Significance: Clinical and mechanistic data identify germline genetic variants in VEGFA and FLT4 as markers of survival in patients with metastatic renal cell carcinoma.
Older Adults and Diabetes Prevention Programs in the Veterans Health Administration
Authors: Pearl G. Lee, Laura J. Damschroder, Robert Holleman, Tannaz Moin, Caroline R. Richardson
Journal: Diabetes Care (2018)

OBJECTIVE To investigate whether older veterans enrolled in two diabetes prevention programs (DPPs) in the Veterans Health Administration will have similar weight loss as younger veterans. RESEARCH DESIGN AND METHODS Post hoc analysis of data from two prospective, pragmatic, nonrandomized studies of behavioral weight management interventions that were delivered in-person (Department of Veterans Affairs [VA]-DPP) or online (Online-DPP), comparing participation and weight loss between participants aged ≥65 years (N = 120) vs. &amp;lt;65 years (N = 258). RESULTS Over 70% of participants in both age groups completed eight or more sessions within 6 months; a higher proportion completed eight or more sessions in the Online-DPP intervention than in the VA-DPP intervention (P &amp;lt; 0.05). The overall weight changes at 6 and 12 months were similar across the two age groups: ∼5 kg or 5% weight loss compared with baseline (P &amp;gt; 0.05). CONCLUSIONS DPPs delivered in person or online can be similarly effective in older and younger veterans. Online programs may be an important means to improve the reach of DPPs for older adults.
The Trump Administration’s Actions to Address the Opioids Public Health Crisis–Reply
Authors: Richard G. Frank, Rebecca L. Haffajee
Journal: JAMA Psychiatry (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry 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 Psychiatry journal
Pharmacomechanical Catheter Directed Thrombolysis for Pregnancy Related Proximal Lower Extremity Deep Venous Thrombosis: Effectiveness in the Prevention of Post Thrombotic Syndrome
Authors: Galia Spectre, Allan Bloom, Batia Roth, David Varon, Yosef Kalish, Nael Da'as, Tal Tzitershpiler
Journal: Blood (2016)
Abstract 19326: Cardiac-specific Deletion of Ulk1, but not Atg7, Impairs Mitophagy in the Heart During Ischemia
Authors: Toshiro Saito, Junichi Sadoshima
Journal: Circulation (2017)

The removal of damaged mitochondria by mitophagy is essential for maintaining the quality of mitochondria in the heart during stress, such as ischemia. Activation of mitophagy, its underlying mechanism, and its functional significance have not been clearly demonstrated in the heart during ischemia. We generated cardiac-specific transgenic mice expressing Mito-Keima, a pH-sensitive indicator (Tg-Mito-Keima), where acidic dots of Mito-Keima were induced in the heart in response to TAT-Beclin 1 (20 mg/kg), a peptide known to induce autophagy. In order to investigate the roles of Atg7 and Ulk1, key regulators of autophagy, in mediating mitophagy, we crossed wild-type (WT), cardiac-specific atg7 knockout (atg7cKO), or cardiac-specific ulk1 knockout, (ulk1cKO) mice with Tg-Mito-Keima. Then, Tg-Mito-Keima, Tg-Mito-Keima-atg7cKO, and Tg-Mito-Keima-ulk1cKO mice were subjected to 48 hours of starvation (STV) or ischemia. We quantified the dots with a high 560nm/440nm ratio, which indicate lysosomal translocation of...
Widespread Selection for Oncogenic Mutant Allele Imbalance in Cancer
Authors: Craig M. Bielski, Mark T.A. Donoghue, Mayur Gadiya, Aphrothiti J. Hanrahan, Helen H. Won, Matthew T. Chang, Philip Jonsson, Alexander V. Penson, Alexander Gorelick, Christopher Harris, Alison M. Schram, Aijazuddin Syed, Ahmet Zehir, Paul B. Chapman, David M. Hyman, David B. Solit, Kevin Shannon, Sarat Chandarlapaty, Michael F. Berger, Barry S. Taylor
Journal: Cancer Cell (2018)