tbuckley/cabot-search huggingface dataset:
Epigenetic inactivation of EGFR by aberrant promoter methylation: implications for combining hypomethylating drugs and EGFR inhibitors
Authors: Alberto J. Montero, Marcela Diaz-Montero, Li Mao, Emile M. Youssef, Marcos Estecio, Lanlan Shen, Jean-Pierre Issa
Journal: Cancer Research (2005)

2711  Introduction: The epidermal growth factor receptor (EGFR) is a member of the HER/ERB-B family of transmembrane receptor kinases. Overexpression of EGFR confers advantages in cell proliferation, survival, and migration. In primary tumors, EGFR over-expression has been reported to correlate with decreased survival in multiple cancers (e.g., head and neck, breast, ovarian, and esophageal cancers). However, in a fraction of these solid tumors little or no expression of EGFR is observed. Aberrant CpG island methylation and associated transcriptional silencing are common in solid tumors. Since EGFR has a large CpG island that extends into exon-1, we hypothesized that methylation of EGFR was an important mechanism in transcriptional silencing. Materials and methods: Methylation analysis of EGFR CpG island in exon 1 was ascertained by COBRA, pyrosequencing, and bisulfite sequencing. Breast cancer cell lines CAMA-1 and MB-453 were treated with decitabine and re-expression of EGFR was determined by RT-PCR. Induction of apoptosis after treatment with gefitinib and decitabine alone or in combination was assayed by annexin V/PI staining followed by flow cytometry analyses. Results: The methylation status of EGFR was examined in a series of solid tumor cell lines and normal tissues. Among the cell lines examined, dense methylation (90%) was found in the breast cancer cell line CAMA-1, and a moderate degree of methylation (30-50%) was observed in the breast cancer cell lines MD-435 and MD-453. Transcriptional silencing of EGFR in these cell lines closely correlated with methylation. By contrast, no methylation of the HER-2/neu CpG island, was detected in these breast cancer cell lines. Aberrant methylation of EGFR (>10%) was also found in a subset of unselected primary breast tumors (3/14), as well as in head and neck (6/17) and lung (6/54) tumors. However, no methylation of EGFR was observed in any of the assayed normal tissues. Treatment with decitabine resulted in the re-expression of EGFR in both CAMA-1 and MD-453. Both cell lines are relatively resistant to killing by the EGFR inhibitor gefitinib. However, after treatment with a combination of decitabine and gefitinib, a synergistic effect on the induction of apoptosis was observed. Conclusions: EGFR is methylated in some cancers, which correlates with transcriptional silencing. Co-treatment of EGFR negative breast carcinoma cell lines with gefitinib and the hypomethylating agent decitabine is synergistic in the induction of apoptosis.
A Novel Reduced Intensity Conditioning Can Induce a High Incidence of Sustained Donor Engraftment After Double Unit Cord Blood Transplantation (CBT) without Anti-Thymocyte Globulin
Authors: Doris M Ponce, Craig Sauter, Marissa Lubin, Anne Marie Gonzales, Glenn Heller, Hugo Castro-Malaspina, Sergio Giralt, Nancy A. Kernan, Esperanza B. Papadopoulos, Andromachi Scaradavou, Juliet N. Barker
Journal: Blood (2010)
Ebv-positive and ebv-negative post-transplantation lymphoproliferative disorders: two different disorders?
Authors: Thomas Tousseyn, Peter Van Loo, J. Finalet Ferreiro, An Herreman, Daan Dierickx, Gregor Verhoef, P Matthys, Iwona Wlodarska, Xavier Sagaert, C De Wolf-Peeters
Journal: Annals of Oncology (2011)
Abstract 1305: <i>In vitro</i> analysis of T cells effector vs regulatory function in patients with metastatic melanoma and its correlation to patient outcome
Authors: Upendra P. Hegde, Sidharth S. Jha, Nitya G. Chakraborty
Journal: Cancer Research (2015)

Abstract Back ground: Metastatic melanoma is an aggressive tumor of the epidermal melanocytes with high mortality rates in patients. The anti- melanoma immune response has been extensively studied while immune based treatment strategies are showing promising activity in melanoma patients. A number of immune characteristics are evaluated as predictive and prognostic biomarker. Methods: With approval from Institution's regulatory board, we analyzed T cells from peripheral blood of 12 metastatic melanoma patients for baseline frequency of T cells reacting against melanoma related Mart-1 27-35 epitope. We expanded CD 8+ T lymphocytes by exposing them to the Mart-127-35 epitope pulsed on autologous mononuclear cell derived antigen presenting cells ex vivo. Using magnetic bead separation techniques, we also isolated from the peripheral blood CD4+CD25+ (naturally occurring Treg) and CD4+CD25- cells and analyzed in vitro proliferation of CD4+CD25- T cells in response to anti CD3 antibody and PHA and analyzed the effects of CD4+CD25+ cells on their proliferation. Finally, we induced CD4+ T cells into Th1 or Th2 type responses and analyzed their function in vitro. Results: There was variable degrees of CD8+effector T lymphocytes responses to the antigens in in vitro cultures from all the patients studied and their cytokine profile noted. The percentage of nTreg activity in the PBL averaged about 5% that demonstrated suppression of the CD4+CD25- T cells proliferation in response to anti CD3 antibody in about 50% of patients, but lacked suppression activity in about 50% of the patients. It was possible to generate Th1 type cells from all the patients but generation of the Th2 type cells was limited to 50%. Favorable immune characteristics were observed in majority of the patients who are responding to the treatment. Conclusion: Our findings suggest that in vitro functional T cell immune characteristics could be examined in patients diagnosed with metastatic melanoma. Examination of these characteristics in larger number of patients diagnosed with melanoma might provide predictive marker for immune intervention. Citation Format: Upendra P. Hegde, Sidharth S. Jha, Nitya G. Chakraborty. In vitro analysis of T cells effector vs regulatory function in patients with metastatic melanoma and its correlation to patient outcome. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1305. doi:10.1158/1538-7445.AM2015-1305
Regulation of Head and Neck Squamous Cancer Stem Cells by PI3K and SOX2
Authors: Stephen B. Keysar, Phuong N. Le, Bettina Miller, Brian C. Jackson, Justin R. Eagles, Cera Nieto, Jihye Kim, Binwu Tang, Magdalena J. Glogowska, J. Jason Morton, Nuria Padilla-Just, Karina Gomez, Emily Warnock, Julie Reisinger, John J. Arcaroli, Wells A. Messersmith, Lalage M. Wakefield, Dexiang Gao, Aik-Choon Tan, Hilary Serracino, Antonio Jimeno
Journal: JNCI Journal of the National Cancer Institute (2016)

We have an incomplete understanding of the differences between cancer stem cells (CSCs) in human papillomavirus-positive (HPV-positive) and -negative (HPV-negative) head and neck squamous cell cancer (HNSCC). The PI3K pathway has the most frequent activating genetic events in HNSCC (especially HPV-positive driven), but the differential signaling between CSCs and non-CSCs is also unknown.We addressed these unresolved questions using CSCs identified from 10 HNSCC patient-derived xenografts (PDXs). Sored populations were serially passaged in nude mice to evaluate tumorigenicity and tumor recapitulation. The transcription profile of HNSCC CSCs was characterized by mRNA sequencing, and the susceptibility of CSCs to therapy was investigated using an in vivo model. SOX2 transcriptional activity was used to follow the asymmetric division of PDX-derived CSCs. All statistical tests were two-sided.CSCs were enriched by high aldehyde dehydrogenase (ALDH) activity and CD44 expression and were similar between HPV-positive and HPV-negative cases (percent tumor formation injecting ≤ 1x10(3) cells: ALDH(+)CD44(high) = 65.8%, ALDH(-)CD44(high) = 33.1%, ALDH(+)CD44(high) = 20.0%; and injecting 1x10(5) cells: ALDH(-)CD44(low) = 4.4%). CSCs were resistant to conventional therapy and had PI3K/mTOR pathway overexpression (GSEA pathway enrichment, P < .001), and PI3K inhibition in vivo decreased their tumorigenicity (40.0%-100.0% across cases). PI3K/mTOR directly regulated SOX2 protein levels, and SOX2 in turn activated ALDH1A1 (P < .001 013C and 067C) expression and ALDH activity (ALDH(+) [%] empty-control vs SOX2, 0.4% ± 0.4% vs 14.5% ± 9.8%, P = .03 for 013C and 1.7% ± 1.3% vs 3.6% ± 3.4%, P = .04 for 067C) in 013C and 067 cells. SOX2 enhanced sphere and tumor growth (spheres/well, 013C P < .001 and 067C P = .04) and therapy resistance. SOX2 expression prompted mesenchymal-to-epithelial transition (MET) by inducing CDH1 (013C P = .002, 067C P = .01), followed by asymmetric division and proliferation, which contributed to tumor formation.The molecular link between PI3K activation and CSC properties found in this study provides insights into therapeutic strategies for HNSCC. Constitutive expression of SOX2 in HNSCC cells generates a CSC-like population that enables CSC studies.
Class I HLA haplotypes form two schools that educate NK cells in different ways
Authors: Amir Horowitz, Zakia Djaoud, Neda Nemat-Gorgani, Jeroen Blokhuis, Hugo G. Hilton, Vivien Béziat, Karl-Johan Malmberg, Paul J. Norman, Lisbeth A. Guethlein, Peter Parham
Journal: Science Immunology (2016)

Individuals heterozygous for HLA haplotypes have increased NK cell diversity because of distinct education pathways.
P2-046: To overcome T790M associated EGFR TKI resistance by addition of mono-clonal antibodies against HER-1 and/or HER-2 receptors
Authors: Tony S. Mok, Eve Choi, Cesar Wong, Linda Leung, Philip Lui, Kai Fai To, Kwok Chi Lam, Vivian Lui
Journal: Journal of Thoracic Oncology (2007)
P1-109: Genetic metabolic polymorphisms and risk of pleural mesothelioma
Authors: Stefano Landi, Fabio Bottari, Monica Neri, Roberto Barale, Marcello Ceppi, Rosangela Filiberti, Paola Scaruffi, Luciano Mutti, Riccardo Puntoni
Journal: Journal of Thoracic Oncology (2007)
The Emerging Role of B Cells in Tumor Immunity
Authors: Peiling Tsou, Hiroyuki Katayama, Edwin J. Ostrin, Samir M. Hanash
Journal: Cancer Research (2016)

There is increasing evidence supporting a role for B cells in tumor immunology. Paraneoplastic syndromes occurring before a cancer diagnosis have pointed to the potential for harnessing the humoral immune response for early cancer detection. The presence of tumor-infiltrating B lymphocytes has been linked to a favorable clinical outcome in many types of cancers. However, B cells represent a heterogeneous population with functionally distinct subsets, and the balance among subtypes impacts tumor development. Here, we review recent findings related to B cells and to the humoral immune response in cancer and their translational significance. Cancer Res; 76(19); 5597-601. ©2016 AACR.
Twenty Years of Global Surveillance of Antituberculosis-Drug Resistance
Authors: Matteo Zignol, Anna S. Dean, Dennis Falzon, Wayne van Gemert, Abigail Wright, Armand van Deun, Françoise Portaels, Adalbert Laszlo, Marcos A. Espinal, Ariel Pablos-Méndez, Amy Bloom, Mohamed A. Aziz, Karin Weyer, Ernesto Jaramillo, Paul Nunn, Katherine Floyd, Mario C. Raviglione
Journal: New England Journal of Medicine (2016)

The NEJM Image Challenge app brings a popular online feature to the smartphone.Optimized for viewing on the iPhone and iPod Touch, the Image Challenge app lets you test your diagnostic skills anytime, anywhere.The Image Challenge app randomly selects from 300 challenging clinical photos published in NEJM, with a new image added each week.View an image, choose your answer, get immediate feedback, and see how others answered.The Image Challenge app is available at the iTunes App Store.
Abstract 3598: Selective internal radiation (SIRT) is most effective when comparing local treatment to control progressive liver metastases of gastro-intestinal stromal tumors beyond treatment with tyrosine kinase inhibitors
Authors: Peter Hohenberger, Nils Rathmann, Franka Menge, Maliha Sadick, Stefan Schönberg, Steffen Diehl
Journal: Cancer Research (2015)

Abstract Objective: The liver and the peritoneum are the main area of metastatic spread in gastrointestinal stromal tumors (GIST). Liver surgery plays a minor role for hepatic metastases in comparison to f.e. colorectal cancer. However, once the metastases are resistant to 1st line TKI, surgery, 2nd line therapy, interventional ablation techniques like RFA or selective internal radiation therapy (SIRT) are treatment options. We were interested to analyze the contribution of the different modalities in controlling hepatic progression. Methods: 731 pts with biopsy proven GIST were followed since 2004 (median follow-up 43.6 months); data were prospectively documented. There were 337 males (46.1%) and 101 (13.8%) pts. presented with M1 disease initially. Of the remaining 630 pts, 358 pts (56.8%) developed tumor recurrence after a median time interval of 22 months. 312/358 pts (87%) developed metastases within the abdomen: liver n = 96, peritoneal n = 97, liver+peritoneal n = 78, locoregional n = 10, locoreg.+hep/per n = 21. Imatinib was the initial treatment in all patients with M1 disease. Results: Out of 205 patients with liver metastases, 118 remained controlled by drug therapy or showed multi-site progression. In the remaining 87 pts., 26 pts each underwent liver resection or 2nd/3rd line drug therapy (sunitinib, regorafenib), 22 pts had RFA and 13 pts were treated by SIRT. Follow-up was done via dynamic MRI and contrast-enhanced (CE)-CT. The median hepatic-progression free survival (H-PFS) was 15.9 months (4-29) after SIRT (with 3 CR, 6 PR), however, only 5.6 (range, 2 - 13) months after 2nd line drug, 8.2 (3-15) months after surgery, and 7.7 (5-14) months after RFA, p&amp;lt;0.02. Conclusion: 90Y radiation loaded particles (SIRT) provides the best hepatic progression free survival when compared to 2nd line drugs, RFA or even surgery in imatinib resistant GIST liver metastases. The effect could be mediated by eliminating small (subclinical, micro-) metastases. In patients known to have a GIST resistant to known TKIs, such as wildtype (non-KIT, non-PDGFRA mutated f.e. NF1-associated) lesions, SIRT could be used in earlier treatment lines. Citation Format: Peter Hohenberger, Nils Rathmann, Franka Menge, Maliha Sadick, Stefan Schönberg, Steffen Diehl. Selective internal radiation (SIRT) is most effective when comparing local treatment to control progressive liver metastases of gastro-intestinal stromal tumors beyond treatment with tyrosine kinase inhibitors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3598. doi:10.1158/1538-7445.AM2015-3598
Lenalidomide (LEN)-melphalan-prednisone induction followed by LEN maintenance (MPR-R) in newly diagnosed multiple myeloma (NDMM) elderly patients (Pts) with moderate renal impairment (RI): MM-015 trial post-hoc analysis.
Authors: John V. Catalano, Antonio Palumbo, Katja C. Weisel, Meletios A. Dimopoulos, Michel Delforge, Joan Blade, Maria Teresa Petrucci, Martin Kropff, Roman Hajek, Christian Jacques, Zhinuan Yu, Lindsay Herbein, Michele Cavo
Journal: Journal of Clinical Oncology (2013)

8544 Background: The MM-015 pivotal phase III trial showed significant PFS benefit for MPR-R (31 mos) vs. MPR (14 mos) or MP (13 mos; both p &lt; 0.001) followed by placebo in NDMM pts aged ≥ 65 years. As NDMM pts with RI have poor prognosis, this retrospective analysis studied the efficacy and safety of MPR-R in pts with creatinine clearance (CrCl) &lt; 60 mL/min. Methods: LEN starting dose for induction/maintenance was 10 mg/day (D1–21 of a 28-day cycle). Dose adjustments were not recommended for pts with RI. CrCl was calculated using the Cockcroft-Gault equation. Pts with severe RI (serum Cr &gt; 2.5 mg/dL [221 μmol/L]) were excluded from the trial. Results: Pts with CrCl &lt; 60 mL/min (median 47, interquartile range [IQR] 38–55) were included in this analysis: 51% MPR-R, 45% MPR, and 49% MP. Median PFS was significantly higher with MPR-R (26 mos [95% CI 14–48]) vs. MPR (13 mos [95% CI 12–15]) or MP (14 mos [95% CI 12–16]; both p &lt; 0.001). In a Cox proportional model of PFS, CrCl &lt; 60 mL/min was not identified as a negative prognostic factor (p = 0.69). The most common Gr 4 adverse events (AEs) were hematologic and occurred predominantly during induction and are shown in the Table for pts with or without moderate RI. The number of deaths on study was similar: 10% (MPR-R), 7% (MPR), and 8% (MP); deaths associated with RI or disease progression were reported in ≤ 1% of pts with RI across the arms. Conclusions: The benefit of continuous LEN treatment with MPR-R is not compromised in NDMM pts with moderate RI, consistent with the overall trial results. CrCl and AEs should be monitored closely in this population. Clinical trial information: NCT00405756. [Table: see text]
Overlap between maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms among cutaneous adverse drug reactions in a dermatology ward
Authors: M. Pinto Gouveia, A. Gameiro, I. Coutinho, N. Pereira, J.C. Cardoso, M. Gonçalo
Journal: British Journal of Dermatology (2016)

Inpatients with cutaneous adverse drug reactions (CADR) with overlapping features between maculopapular exanthema (MPE) and drug reaction with eosinophilia and systemic symptoms (DRESS) were examined.To characterize patients with exanthema and few systemic symptoms not meeting the criteria for DRESS [overlapping MPE-DRESS (MP/DR)].We undertook a comparative analysis of clinical and laboratory features of patients with MPE, MP/DR and DRESS (2008-12).We identified 132 inpatients (85 women/47 men, mean age 64·0 ± 17·7 years) with CADR, 37 with DRESS, 28 with MPE, 34 with MP/DR and 33 with other patterns. There were no significant differences in sex, age or concomitant diseases. Allopurinol was the main cause of DRESS (40·5%) and MP/DR (29·4%); antimicrobials were the main cause in MPE (35·7%). In MP/DR the latency period (18·06 ± 13·17 days) was significantly longer than in MPE but shorter than in DRESS. Although hospitalization time was similar to DRESS (13·26 ± 7·41 days), duration of therapy and follow-up in MP/DR was shorter. Exanthema/erythroderma were frequently associated with facial oedema in MP/DR (73·5%) and DRESS (89·2%) but only in 42·0% of patients with MPE. MP/DR histopathology showed keratinocyte vacuolization and perivascular and interstitial infiltrate of lymphocytes, eosinophils and neutrophils, similar but milder than in DRESS, with less interface dermatitis, exocytosis and spongiosis. DRESS was associated with liver involvement (78·4%) and eosinophilia (78·4%), but only in 64·7% and 11·8%, respectively, of patients with MP/DR.An overlapping pattern between MPE and DRESS was identified and characterized. There may be a continuum spectrum between MPE and DRESS.
Optical Imaging of Mesenchymal Epithelial Transition Factor (MET) for Enhanced Detection and Characterization of Primary and Metastatic Hepatic Tumors
Authors: Shadi A. Esfahani, Pedram Heidari, Sun A. Kim, Shuji Ogino, Umar Mahmood
Journal: Theranostics (2016)

Purpose: To assess optical imaging of Mesenchymal-Epithelial Transition factor (MET) for delineation and characterization of intrahepatic models of human hepatocellular carcinoma (HCC) and metastatic colorectal cancer (CRC), and thereby demonstrate its potential use in precision oncology. Materials and Methods:MET expression in human CRC and HCC was assessed in tissue microarrays.We used GE-137, a modified cyanine 5-tagged peptide for MET targeting.HepG2 and Huh-7 (HCC) and HT-29 (CRC) cells with MET overexpression, and LNCaP cells (negative control) with minimal MET expression were incubated with the probe.Correlation between the relative fluorescence signal intensity and cellular MET expression level was assessed.Flow cytometry was used to assess probe specific binding and dissociation constant (Kd).Orthotopic xenograft models of human HCC and metastatic CRC were generated in nu/nu mice by subcapsular implantation of cells.Epifluorescence imaging was performed to capture the changes in deferential probe accumulation at different time points after injection.Target-to-liver background ratio (TBR) was calculated and the probe biodistribution within different organs was assessed.Histopathologic analysis of extracted xenografts was performed to correlate the tumors MET expression with probe uptake by cancer cells.Results: Approximately 91.5% of HCC and 81% of CRC microarray cores showed MET expression.HCC and CRC cells incubated with the probe showed substantial fluorescence compared to control LNCaP, with strong correlation between fluorescence signal and MET expression (R 2 = 0.99, p < 0.001).Probe binding affinity to MET (Kd) was measured to be 2.9 ± 0.36 nM.Epifluorescence imaging showed intense uptake in subcapsular tumors with peak TBR of 5.46 ± 0.46 in Huh-7, 3.55 ± 0.38 in HepG2, and 15.93 ± 0.61 in HT-29 orthotopic xenografts at 4 hours post-injection (mean ± standard deviation).We demonstrated that in vivo probe uptake in xenografts is specific and can be blocked when co-injected with unlabeled peptide; for instance the epifluorescence TBR is reduced from 13.5 ± 1.2 to 1.7 ± 0.3 (p < 0.05) in HT-29 and from 5.3 ± 0.8 to 1.4 ± 0.2 (p < 0.05) in Huh-7 xenografts after co-injection with unlabeled peptides.Biodistribution studies showed predominantly renal clearance of the probe.Conclusion: Optical imaging of MET resulted in high TBR in animal models of primary and metastatic hepatic tumors suggesting its utility for procedural guidance.
Call to Action on Neurotoxin Exposure in Pregnant Women and Children
Authors: Jennifer Abbasi
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cardiomyocyte-specific endothelial Nitric Oxide synthase overexpression limits left ventricular remodeling after myocardial infarction in mice
Authors: SP Janssens, Luc Schoonjans, Pieter Vermeersch, Peter Pokreisz, Marc Tjwa, Marijke Pellens, H Gillijns, Frans Van de Werf, Desire Collen, KD Bloch
Journal: Circulation (2002)