tbuckley/cabot-search huggingface dataset:
Expression of hGSTA1 in stably transfected V79MZ cells co-expressing hCYP1B1 or hCYP1A1 confers variable resistance to cytotoxicity of dibenzo[a,l]pyrene (DB[a,l]P) or its dihydrodiol metabolite
Authors: Sandra L. Leone-Kabler, Charles S. Morrow, Johannes Doehmer, Alan J. Townsend
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1372 

Cytochrome p450s (CYP) are phase I enzymes that catalyze activation of a wide range of carcinogens to more reactive electrophilic metabolites. Glutathione-S-transferases (GSTs) are phase II enzymes that can conjugate glutathione (GSH) to intermediate metabolites, thus detoxifying these reactive compounds. Either human CYP1A1 or CYP1B1 can activate DB[a,l]P to dibenzo[a,l]pyrene-11,12-dihydrodiol-13,14-epoxide (DB[a,l]PDE); however, DB[a,l]P has previously shown higher cytotoxicity in cells expressing human P4501A1. Further, human GSTA1-1 is the most effective of the GST isoforms in conjugating (-)-anti-DB[a,l]PDE with GSH. We developed V79MZ hamster lung fibroblasts stably transfected with either human P4501B1 (V79MZh1B1), or human P4501A1 (V79MZh1A1), alone or in combination with human GST alpha-1 (hGSTA1-1) and used them to examine GST protection against DB[a,l]P cytotoxicity.As expected, DB[a,l]P had higher cytotoxicity in V79MZh1A1 (IC50 = 2.7 nM, compared to 6.0 nM in V79MZh1B1). Expression of hGSTA1-1 conferred 2-fold resistance to cytotoxicity in the hCYP1A1-expressing cells, relative to control V79MZ cells expressing hCYP1A1 alone. In V79MZh1B1 cells (expressing hCYP1B1), added expression of hGSTA1-1 conferred a 5-fold protection relative to cells expressing hCYP1B1 alone. When cells were exposed to (+/−)DB[a,l]P-11, 12-dihydrodiol, again V79MZh1A1 was more sensitive to cytotoxicity than V79MZh1B1 (IC50 = 0.7 nM compared to 4.8 nM respectively). The expression of hGSTA1-1 conferred a slight (1.3-fold) protection in the cells expressing human P4501A1, but in the V79MZ cells expressing hCYP1B1, the GSTA1-1 conferred a robust 9-fold protection (both relative to the respective controls expressing hCYP1A1 or hCYP1B1). These findings demonstrate that: a) the relative protection by hGSTA1 against cellular toxicity of DB[a,l]P is much more effective when it is activated by hCYP1B1 than by hCYP1A1; and b) in cells expressing hCYP1B1, the fold-resistance conferred by hGSTA1 expression against the toxicity of DB[a,l]P-diol is twice that conferred against the parent compound DB[a,lP. In view of the known variations in expression of these genes among human tissues, these findings have implications for differential tissue-specific protection by GSTA1 against DB[a,l]P and possibly other polycyclic aromatic hydrocarbon carcinogens a
3D Near‐Field Electrospinning of Biomaterial Microfibers with Potential for Blended Microfiber‐Cell‐Loaded Gel Composite Structures
Authors: Pouria Fattahi, Jordan T. Dover, Justin L. Brown
Journal: Advanced Healthcare Materials (2017)

This paper describes the development of a novel low-cost and efficient method, 3D near-field electrospinning, to fabricate high-resolution, and repeatable 3D polymeric fiber patterns on nonconductive materials with potential use in tissue engineering. This technology is based on readily available hobbyist grade 3D printers. The result is exquisite control of the deposition of single fibers in an automated manner. Additionally, the fabrication of various fiber patterns, which are subsequently translated to unique cellular patterns, is demonstrated. Finally, poly(methyl methacrylate) fibers are printed within 3D collagen gels loaded with cells to introduce anisotropic properties of polymeric fibers within the cell-loaded gels.
Neuroleptics for Delirium: More Research is Needed—Reply
Authors: Meera R. Agar, Brian Draper, Gideon A. Caplan
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
Prospective Comparative Study between Two Anastomotic Techniques – Early Significant Dysphagia Requiring Endoscopic Dilatation after Two Stage Oesophagectomy
Authors: PC Munipalle, BR Gopinath, PA Davis, YKS Viswanath
Journal: Endoscopy (2006)

Aims: Oesophago-gastric anastomosis with gastric transposition is the commonest method of reconstruction following two-stage oesophagectomy (TSO) for oesophageal cancer but the choice of anastomotic technique (Hand sewn vs. stapled) is often debatable.
Mitochondrial Genomic Backgrounds Affect Nuclear DNA Methylation and Gene Expression
Authors: Carolyn J. Vivian, Amanda E. Brinker, Stefan Graw, Devin C. Koestler, Christophe Legendre, Gerald C. Gooden, Bodour Salhia, Danny R. Welch
Journal: Cancer Research (2017)

Mitochondrial DNA (mtDNA) mutations and polymorphisms contribute to many complex diseases, including cancer. Using a unique mouse model that contains nDNA from one mouse strain and homoplasmic mitochondrial haplotypes from different mouse strain(s)-designated Mitochondrial Nuclear Exchange (MNX)-we showed that mtDNA could alter mammary tumor metastasis. Because retrograde and anterograde communication exists between the nuclear and mitochondrial genomes, we hypothesized that there are differential mtDNA-driven changes in nuclear (n)DNA expression and DNA methylation. Genome-wide nDNA methylation and gene expression were measured in harvested brain tissue from paired wild-type and MNX mice. Selective differential DNA methylation and gene expression were observed between strains having identical nDNA, but different mtDNA. These observations provide insights into how mtDNA could be altering epigenetic regulation and thereby contribute to the pathogenesis of metastasis. Cancer Res; 77(22); 6202-14. ©2017 AACR.
Early mortality in Australian, Canadian and Spanish scleroderma patients: rationale for establishing a multi-national inception cohort of patients with systemic sclerosis
Authors: Y. Hao, M. Hudson, P. Carreira, W. Stevens, C. Rabusa, S. Tatibouet, L. Carmona, B. Joven, S. Proudman, M. Baron, M. Nikpour
Journal: Arthritis & Rheumatology (2014)
Lymphocyte-to-monocyte ratio (LMR) is prognostic factor for selection of neoadjuvant treatment in locally advanced rectal cancer patients: Sub-set analysis of Polish-2 study
Authors: Mariola Winiarek, Sebastian Rybski, Mateusz Spalek, Jacek Krynski, Leszek Zajac, Ewa Kosakowska, Jacek Zwolinski, Andrzej Rutkowski, Wojciech Michalski, Krzysztof Bujko, Lucjan Wyrwicz
Journal: Annals of Oncology (2017)
Impact of prognostic factors on long-term outcomes in metastatic breast cancer (MBC) patients (pts) receiving bevacizumab (B) plus paclitaxel as first-line cytotoxic treatment.
Authors: Andreas Schneeweiss, Marcus Schmidt, Frank Gerhard Foerster, Matthias Geberth, Hans Tesch, Peter Klare, Claudia Schumacher, Wiebke Hollburg, Ulrike Soeling, Bahriye Aktas, Andreas Kutscheidt, Sherko Kümmel
Journal: Journal of Clinical Oncology (2014)

e12007 Background: B combined with chemotherapy (CT) significantly improves progression-free survival (PFS) and response rate (RR) vs CT alone in the first-line treatment of HER2-negative MBC. In a large German prospective, non-interventional study, we examined the impact of standard prognostic factors in a population of pts homogeneously treated with an antibody/taxane combination. Methods: Pts who had received no prior CT for their MBC received B+paclitaxel per the European label. Efficacy and safety were documented in detail for up to 1 year (or until progression, death, or B discontinuation, if earlier), with subsequent retrieval of long-term follow-up. Results: By April 2013, final data were available for 865 pts, with PFS events recorded in 715 pts (83%) and OS events in 524 pts (61%). The prognostic effect of various baseline characteristics is presented in the table. Overall best response (CR+PR) does generally show no major association to the factors analyzed, except for a lower efficacy in triple negative disease (TNBC) (51% vs 65%). Moreover, pts with prior adjuvant taxane showed a further, significant drop to a median PFS of only 7.4 months. Conclusions: The mature data from this study show strong prognostic impact of TNBC, type and number of involved sites, and experiencing relapse after adjuvant chemotherapy. Additional prognostic parameters and the results of multivariate models will be presented at the meeting. Characteristic PFS (months, medians) OS (months, medians) Age, < 35 vs ≥ 35 years 6.0 vs 9.7 (p= .15) 23.7 vs 21.6 (p= .94) Primary M1 disease, yes vs no 9.5 vs 9.4 (p= .49) 27.2 vs 19.7 (p= .029) Disease-free interval, ≤ 1 vs > 1 year 8.7 vs 10.3 (p= .17) 20.9 vs 21.8 (p= .37) Metastatic sites, < 3 vs ≥ 3 10.2 vs 8.3 (p = .015) 23.2 vs 19.0 (p= .034) Visceral metastasis, yes vs no 9.2 vs 11.0 (p= .012) 20.1 vs 26.0 (p= .022) Hormone receptor, positive vs negative 10.3 vs 8.6 (p= .0026) 23.9 vs 16.9 (p< .0001) TNBC, yes vs no 7.9 vs 10.2 (p= .00044) 15.8 vs 23.7 (p< .0001) Prior (neo)adjuvant CT, yes vs no 9.0 vs 11.0 (p= .00042) 17.5 vs 23.4 (p< .0001) Prior palliative endocrine therapy, yes vs no 9.8 vs 9.6 (p= .27) 21.7 vs 21.4 (p= .70)
the Role of MSCs in the Development of Acute Myeloid Leukemia
Authors: Yahya Saleh Al-Matary, Lacramioara Botezatu, Robert Fernando Lams, Aniththa Thivakaran, Renata Köster, Judith Schütte, Ulrich Dührsen, Bertram Opalka, Cyrus Khandanpour
Journal: Blood (2016)
Landscape of genomic alterations (GA) and tumor mutational burden (TMB) in different metastatic melanoma (MM) subtypes.
Authors: Douglas Buckner Johnson, J. Andrew Carlson, Julia Andrea Elvin, Jo-Anne Vergilio, James Suh, Shakti Ramkissoon, Sugganth Daniel, David Fabrizio, Garrett Michael Frampton, Siraj Mahamed Ali, Alexa Betzig Schrock, Byoung Chul Cho, Geoffrey Thomas Gibney, Bartosz Chmielowski, Shridar Ganesan, Janice M. Mehnert, Vincent A. Miller, Phil Stephens, Laurie M. Gay, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2017)

9536 Background: MM is a highly targetable malignancy, with both kinase inhibitors and immunotherapies providing meaningful survival benefit. Different subtypes of mm harbor distinct GA that suggest targeted and immunotherapy options. Methods: Comprehensive genomic profiling was performed in 2,197 MMs for up to 315 cancer-related genes plus introns from 28 genes commonly rearranged in cancer on hybrid-capture, adaptor ligation-based libraries (mean coverage depth &gt; 600X). TMB was calculated from ≥1.11 Mb sequenced DNA. We assessed base substitutions, insertions and deletions (short variants; SV), rearrangements, and copy number changes. Results: We assessed 6 subtypes: routine cutaneous (CT; 90%), desmoplastic (DM: 1%), acral lentiginous (AL; 1%), Spitzoid (SP; 1%), mucosal (MC; 2%) and ocular (OC; 5%). Each group harbored characteristic genomic signatures (Table). BRAFwas mutated in 38% of CT of which 92% were SV GA and 8% were amplifications, fusions or cases with &gt; 1 BRAF GA. High TMB in CT and DM is highly prevalent (42% and 83% with &gt; 20 mut/Mb). BRAFGA were less common in AL (18%), MC (15%), and OC (2%). SP GA were dominated by fusions in BRAF (60%) and other kinases. KIT GA were prominent in MC and AL. TMB for MC and OC mm were very low. Key findings include novel drivers of BRAF inhibitor resistance including BRAFinternal rearrangements and kinase domain duplications. Conclusions: In the largest cohort of mm with NGS to date, genomic profiles and TMB differ across mm subtypes. Highly prevalent BRAF GA (including in the SP variant) and high TMB in CT and DM mm permit effective use of targeted and immunotherapies. Although MC and OC have lower BRAF GA frequency and lower TMB, targetable GA can be present. Novel BRAF inhibitor resistance mechanisms were observed. [Table: see text]
Cholangioscopic imaging: distinguishing good from bad
Authors: Jürgen Pohl
Journal: Endoscopy (2017)

It can be assumed that 30 years ago, clinicians thought that a barium enema was the diagnostic state of the art and represented the ultimate advance in evaluating pathology in the colon. Today, in the era of high definition imaging with colonoscopes, that view seems strange and completely antiquated. But we are possibly now on the verge of a similar technological shift in the evaluation of biliary diseases. Endoscopic retrograde cholangiopancreatography (ERCP) is still the standard procedure for endoscopic evaluation and treatment of diseases in the biliary tract. Like the barium enema, however, black-and-white radiographic imaging has limited sensitivity and specificity, and it is virtually impossible to distinguish between malignant and benign strictures by relying on quite unspecific features of the duct contours at cholangiography. A large study on patients with indeterminate pancreaticobiliary pathology showed sensitivity and specificity rates of 51 % and 54 % for the cholangiographic appearance on its own [1].
Abstract A63: IFNAR1 downregulation during melanoma progression upregulates αv expression and promotes metastasis
Authors: Angelica Ortiz, Yuliya V. Katlinskaya, Kanstantsin V. Katlinski, Serge Y. Fuchs
Journal: Cancer Research (2016)

Abstract The anti-metastatic effects of type 1 interferon (IFN1) prompted its use for adjuvant therapy in malignant melanoma patients at high risk for developing metastasis. While IFN1 adjuvant therapy continues to be the preferred treatment, many patients fail to elicit response to IFN1 treatment and progress to develop distal metastases often resulting in a lethal outcome. We observed downregulation of the IFNAR1 chain of the IFN1 receptor and suppression of IFN1 signaling in genetically engineered mouse melanomas driven by melanocyte-specific activation of Braf and inactivation of Pten. Induction of melanoma in animals expressing IFNAR1 that is deficient in ubiquitination and degradation led to a delayed onset of the disease and decreased number of local metastases. Remarkably, no distant metastases were found in these mice despite substantial primary tumor burden. Gene set enrichment analysis demonstrated a dramatic loss of the αv integrin pathway signature in mice harboring stabilized IFNAR1. Conversely, melanomas induced in Ifnar1 knockout mice yielded transplantable cell lines that displayed high levels of αv expression. Restoring IFNAR1 expression in these cells led to the loss of αv expression. We discuss the role of these mechanisms in melanoma metastasis and refractoriness to IFN1-based therapy. Citation Format: Angelica Ortiz, Yuliya V. Katlinskaya, Kanstantsin V. Katlinski, Serge Y. Fuchs. IFNAR1 downregulation during melanoma progression upregulates αv expression and promotes metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A63.
07.12 Dicam promotes proliferation and hypertrophic differentiation of chondrocyte through indian hedgehog signalling of primary cilia
Authors: Seung-Woo Han, Hye-Ri Park, Min-Su Han, Eun-Ju Lee, Ji-Ae Jang, Gun-Woo Kim, Youn-Kwan Jung
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Chondrocytes in growth plate is known to respond to hydrostatic loading by increasing Indian hedgehog (Ihh) signalling, and that the primary cilium is required for this mechano-biological signal transduction to occur. Dicam (dual Ig domain containing cell adhesion molecule) was originally cloned from human chondrocyte cell-line, HCS-2/8 cells, but the role during endochondral bone formation and osteoarthritis has not been elucidated. This study reveals that Dicam has a novel function as a modulator of primary cilia-mediated Ihh signalling in chondrocytes. <h3>Materials and methods</h3> Primary chondrocytes and tibia were isolated from limbs of C57BL/6 embryo (E15.5) and used <i>in vitro</i> study. Cartilage-specific Dicam transgenic (Col2-Dicam-Tg) mice were constructed and the phenotype of E15.5 long bone was compared with their wild type-littermates. <h3>Results</h3> Dicam mainly expressed in resting and proliferating chondrocytes in growth plate and it was increased by Pthrp and BMP2 in primary chondrocytes. Gain-of function study with Col2-Dicam-Tg revealed that Dicam increased length of long bones. Col2-Dicam-Tg showed an increased expression of chondrogenic, Col2a1 and proliferating marker, PCNA in immunostaining analysis. In addition, early and late hypertrophic chondrocyte marker, Col10a1 and MMP13, respectively, also increased in Col2-Dicam-Tg compared to wild-type. To elucidate a molecular mechanism of Dicam, we checked the major signalling targets in chondrogenesis, which showed an increased expression of Hhip and Zfp521, the target molecule of Ihh and Pthrp signalling, respectively. Other Ihh signalling molecules such as Ptch1, Gli2, and Gli3 and Ihh itself were also increased by Dicam overexpression in primary chondrocytes. Mechanistically, Dicam was localised to primary cilia of chondrocytes and increased a number of primary cilia and their assembly molecule, IFT88/polaris. Knock-down of IFT88/polaris attenuated the Dicam-mediated increase of length in primary tibia organ culture. In next step, we investigated whether Dicam influences the severity of cartilage degradation in surgically-induced osteoarthritis (OA) model. Dicam was expressed in articular cartilage and its expression level was attenuated in OA cartilage. <h3>Conclusions</h3> Dicam was localised to primary cilia and increased proliferation and hypertrophic differentiation of chondrocytes through Ihh signalling resulting in an increase of bone length <i>In Vivo</i>. <h3>Acknowledgement</h3> This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2013R1A2A2A01069204)
Fat Grafting—More Than Just the Hype
Authors: Scott T. Hollenbeck, E. Shelley Hwang
Journal: JAMA Surgery (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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Comprehensive clinical, pathological and molecular characterization of a cohort of locally advanced rectal cancer patients: Towards an integrative classification for rectal cancer management
Authors: Soledad Iseas, Martin Sendoya Juan, Mariano Golubicki, Mariana Coraglio, Ubaldo Gualdrini, Ana Cabanne, Mirta Kujaruk, Vanesa Mikolaitis, Mariana Rizzolo, Ruben Salanova, Martin Eleta, Stella Irmas, Cecilia Rotondaro, Maximiliano Ink, Fernandez Elmer, Osvaldo Podhajcer, Andrea Llera, Enrique Roca
Journal: Annals of Oncology (2017)
Programmed death-ligand 1 (PD-L1) characterization of circulating tumor cells (CTCs) in muscle invasive and metastatic bladder cancer patients.
Authors: Archana Anantharaman, Terence W. Friedlander, David Lu, Rachel Krupa, Gayatri Premasekharan, Jeffrey Hough, Matthew Edwards, Ryon Graf, Adam Jendrisak, Jessica Louw, Lyndsey Dugan, Dena C. Marrinucci, Ryan Vance Dittamore, Pamela Paris
Journal: Journal of Clinical Oncology (2016)

4527 Background: Recent studies indicate that PD-1 and PD-L1 checkpoint inhibitors have activity in chemotherapy refractory patients with muscle invasive (MIBC) and metastatic (mBCa) bladder cancer. PD-L1 expression on tumor cells or lymphocytes may correlate with response to therapy. To identify potential patients who may benefit from PD-1/PD-L1 targeted immunotherapeutics, we utilized a non-invasive blood test to evaluate PD-L1 protein expression in CTCs and WBCs of bladder cancer patients. Methods: Blood samples from 22 patients with MIBC or mBCa were collected at UCSF and shipped to Epic Sciences. All nucleated cells were subjected to immunofluorescent (IF) staining and CTC identification by fluorescent scanners and algorithmic analysis. Cytokeratin (CK+) expressing CTCs (CK+, CD45-, intact nuclei morphologically distinct from WBCs) as well as CK- CTCs were enumerated and correlated with available clinical data. A subset of patient samples underwent further genetic characterization by FISH. Results: CTCs were detected in 19/22 (86.4%) patients, inclusive of CK(+) CTCs (12/22, 55%), CK(-) CTCs (14/22, 70%), CK(+) CTC Clusters (6/22, 27%), and apoptotic CTCs (12/22, 54%). Seven of 22 (32%) patients had PD-L1(+) CTCs; 4 of these patients had exclusively CK(-)/CD45(-)/PD-L1(+) CTCs. A subset of CTCs were secondarily confirmed as bladder cancer via FISH. High PD-L1(+)/CD45(-) CTC burden was associated with poorer overall survival (HR: 3.29, log-rank p = 0.041) Conclusions: Patients with MIBC and mBCa who have detectable PD-L1(+) CTCs, and patients with high PD-L1(+) CTCs have worse survival compared to patients with low or absent PD-L1 expression.