tbuckley/cabot-search huggingface dataset:
Angelman Syndrome in the<i>Portrait of a Child With a Drawing</i>by Giovanni F. Caroto
Authors: Francesco M. Galassi, Emanuele Armocida, Frank J. Rühli
Journal: JAMA Pediatrics (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 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
Association of somatic mutations in DNA damage repair (DDR) genes with efficacy of platinum-based chemotherapy in advanced urothelial carcinoma.
Authors: Richard Martin Bambury, Emmet Jordan, Emily Craig Zabor, Nancy Bouvier, Hikmat Al-Ahmadie, Mariel Elena Boyd, Stephanie A. Mullane, Eugene K. Cha, Irina Ostrovnaya, David Michael Hyman, Bernard H. Bochner, Maria E. Arcila, David B. Solit, Dean F. Bajorin, Joaquim Bellmunt, Michael F. Berger, Gopa Iyer, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2015)

4532 Background: Platinum-based chemotherapy (PBC) is standard of care in the neoadjuvant and metastatic UC settings. Recent work identified mutations in ERCC2, RB1, FANCC and ATM as potential predictive biomarkers of response. We assessed response to PBC among patients with locally advanced or metastatic UC who underwent pre-treatment tumor genomic sequencing. Methods: 72 patients treated with PBC had exon sequencing of > 200 tumor suppressor/oncogenes using the MSK-IMPACT next generation sequencing assay. Deletions, truncations, frameshift, splice-site and missense alterations were recorded among 33 genes involved in the nucleotide excision repair, homologous repair and Fanconi anemia pathways (Table). Inactivating alterations in RB1 and TP53 were also investigated as potential predictive biomarkers. Baseline clinical parameters, investigator-assessed radiologic response and PFS were recorded. Results: 31(43%) patients had alterations in DDR genes and these were associated with improved PFS (median 11.3 v 6.1 months, HR 0.51, p 0.01). Among 65 evaluable patients, radiologic response was observed in 81% of those with DDR gene alterations vs. 58% in those without (p 0.06). DDR alterations remained a significant predictor for PFS on multivariate analysis (HR 0.45, p 0.004) after adjusting for ECOG performance status, visceral vs nodal metastases, chemotherapy type (cisplatin v carboplatin) and prior perioperative cisplatin. Among 9 patients with deletion, truncation, frameshift or splice-site alterations of DDR genes, 8 achieved PFS >11 months. There was no association between PFS and RB1 (HR 1.37, p 0.32) or TP53 (HR 0.93, p 0.79) alterations. Conclusions: Alteration of DDR genes is associated with improved efficacy in patients receiving 1st line PBC for advanced UC. Further refinement and validation could lead to prospective identification of patients who will respond to PBC, as well as identify patients unlikely to benefit and for whom alternative approaches are warranted. ATM ERCC2 PARP1 ATRX ERCC3 PMS1 BAP1 ERCC4 PMS2 BARD1 ERCC5 POLE BLM FANCA RAD50 BRCA1 MLH1 RAD51 BRCA2 MRE11A RAD51B BRIP1 MSH2 RAD51C CHEK1 MSH6 RAD51D CHEK2 NBN RAD52 FANCC PALB2
Circulating cell-free DNA profiling of patients with advanced urothelial carcinoma of the bladder.
Authors: Rebecca J Nagy, Neeraj Agarwal, Sumati Gupta, Sumanta K. Pal, Petros Grivas, Ulka N. Vaishampayan, Jue Wang, Gurudatta Naik, Richard Burnham Lanman, AmirAli Talasaz, Guru Sonpavde
Journal: Journal of Clinical Oncology (2016)

4528 Background: Urothelial carcinoma of the bladder (UCB) exhibits one of the highest somatic mutation burdens. Circulating cell-free DNA (cfDNA) is obtained non-invasively from peripheral blood and appears detectable in most patients (pts) with advanced UCB. We report cfDNA profiling of patients with advanced UCB using biopsy-free cfDNA sequencing. Methods: Pts with advanced UCB that underwent cfDNA analysis using Guardant360 were identified. A 70-gene cfDNA next generation sequencing (NGS) panel from a CLIA-licensed, CAP-accredited laboratory (Guardant Health, Inc.) offers complete exon sequencing for 29 cancer genes, critical exons in 39 genes and amplifications (16 genes), fusions (6 genes) and indels (3 genes) harvested from 10 mL of peripheral blood. Results: Of 71 patients with advanced UCB, cfDNA was detectable in 61 patients (85.9%). The median age was 70 years (range 45-89). The most common recurrent somatic mutations were in TP53 (n = 35), BRCA1/2 (n = 20), ARID1A (n = 17), FGFR2/3 (n = 17), KRAS/RAF1/BRAF/MAPK (n = 15), and NF1 (n = 12), MET (n = 10) and ERBB2 (n = 10). The most common genes with increased copy numbers were kinase genes (ERBB2, PIK3CA, EGFR, RAF1, BRAF, MET and FGFR1) and cell-cycle controlling genes (MYC, CCNE1, CDK4/6). The cfDNA somatic alteration burden appeared similar to those of other major malignancies. Serial cfDNA profiling of pts receiving chemotherapy revealed the clonal evolution of mutations in genes associated with resistance including BRCA2, NF1 and GATA3. Analysis of additional patients is ongoing in this expanding dataset. Conclusions: cfDNA was frequently detected in patients with advanced UCB, and alterations were most frequently seen in TP53, kinase genes, epigenetic modifiers and cell-cycle controlling genes, which appears similar to those previously reported from muscle-invasive UCB tumor tissue NGS. Given that cfDNA offers a non-invasive means of profiling tumor DNA, identification of the mechanisms of resistance targeted with this test should be evaluated for impact on response.
Abstract 3319: Characterization of the CD44+/CD49f+/CD24- subpopulation in basal-like DCIS cells
Authors: Nadire Duru, Ramkishore Gernapudi, Pang-Kuo Lo, Yuan Yao, Benjamin Wolfson, Yongshu Zhang, Qun Zhou
Journal: Cancer Research (2016)

Abstract The molecular mechanisms responsible for Ductal Carcinoma In Situ (DCIS)-Invasive Ductal Carcinoma (IDC) transition have yet to be elucidated. Due to the lack of molecularly targeted therapies, basal-like DCIS has a high risk of recurrence and progression to invasive and metastatic cancers. In this study, using a human DCIS cell line model and a novel single-cell clonogenic approach, we have identified and characterized the aggressive clones derived from single cells with the CD49f+/CD44+/CD24- surface markers. We found that aggressive clones had enhanced self-renewal, migratory and invasive capacities. The aggressive clones had elevated ALDH activity, lower global DNA methylation and increased expression of stem cell related genes including OCT4 and SOX2. Further mechanistic studies showed that linc-ROR and miR-10b were overexpressed in aggressive clones and are key regulators of their self-renewal and invasive abilities. Finally, we confirmed our in vitro results in vivo, demonstrating that aggressive clones were capable of forming tumors in nude mice, whereas non-aggressive clones were not. We believe that characterization of aggressive clones within the heterogeneous CD49f+/CD44+/CD24- DCIS population and having linc-ROR and miR10b as additional markers to distinguish them from non-aggressive clones would provide the basis to develop new chemoprevention agents. Citation Format: Nadire Duru, Ramkishore Gernapudi, Pang-Kuo Lo, Yuan Yao, Benjamin Wolfson, Yongshu Zhang, Qun Zhou. Characterization of the CD44+/CD49f+/CD24- subpopulation in basal-like DCIS cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3319.
P0005 : The new strategy of autologous liver cell transplantation for acute liver failure after massive hepatectomy: Role of hepatocytes and liver non parenchymal cells
Authors: S. Kita, K. Yasuchika, T. Ishii, H. Katayama, E.Y. Yoshitoshi, S. Ogiso, T. Kawai, K. Yasuda, K. Fukumitsu, M. Mizumoto, S. Uemoto
Journal: Journal of Hepatology (2015)
Abstract 249: Breast cancer cell vesiculation is driven by calpain: implications in cancer therapy
Authors: Jack Taylor, Ritu Jaiswal, Mary Bebawy
Journal: Cancer Research (2016)

Abstract Microparticles (MPs) are small membrane vesicles (0.1 to 1 μm in diameter) released from the plasma membranes of most cell types, (malignant and non-malignant) upon cellular activation or during apoptosis. We discovered that MPs provide a “non-genetic” mechanism for the acquisition of multidrug resistance and increased metastatic capacity in tumour cell populations, whereby they serve as vectors in the intercellular transfer of functional cancer proteins and nucleic acids. By this mechanism, MPs effectively confer the transfer, dissemination and dominance of within cancer cell populations within a matter of hours. The aim of this study was to define the pathways governing membrane vesicle biogenesis in malignant and non-malignant cells with the aim of identifying cancer specific mediators, which could serve as novel therapeutic targets in preventing microvesicle induced deleterious traits in cancer. We preformed a comparative analysis using the non-malignant human brain endothelial cell line (HBEC-D3) cells and drug sensitive and resistant human breast adenocarcinoma cells (MCF-7) and (MCF-7/DX) respectively. Cell surface topography and vesiculation pits were visualized at rest, and in the +/- calcium ionophore, A23187 and the Calpain inhibitor ALLM using contact mode Atomic Force Microscopy (Nanowizard, JPK Instruments, Germany) on fixed cells. We observed that at rest, cells from both malignant cell lines were high vesiculators relative to the HBEC-D3 cells. In the presence of ALLM we observed a direct inhibition of vesiculation in the malignant cells whilst vesiculation was enhanced in the non-malignant cells. Upon the release of calcium from intracellular stores using A23817, we observe an increase in vesiculation across all cell types, however to a greater extent in the HBEC-D3 cells. Interestingly, only upon the release of intracellular calcium in HBEC-D3 cells do we see an inhibition of vesiculation by ALLM. These results clearly demonstrate an alternative pathway governing vesiculation at rest for the non-malignant HBEC-D3 cells. Whereas contrary to this, vesiculation at rest in malignant cells appears to be calpain dependent. Future work aims to validate these findings and examine the presence of distinct pathways of vesiculation in malignant cells relative to non-malignant cells. These results have important implications in defining novel strategies to selectively targeting malignant cells and for the circumvention of deleterious traits acquired through intercellular exchange of extracellular vesicles. Citation Format: Jack Taylor, Ritu Jaiswal, Mary Bebawy. Breast cancer cell vesiculation is driven by calpain: implications in cancer therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 249.
Prognostic Factors for Patients with Diffuse Large B Cell Lymphoma and Transformed Indolent Lymphoma Undergoing Autologous Stem Cell Transplantation in Denmark 2000-2012
Authors: Bente Arboe, Kristina Fruerlund Nielsen, Charlotte Madsen, Rasmus Heje Thomsen, Soeren Ramme Nielsen, Jette Soenderskov Goerloev, Peter de Nully Brown
Journal: Blood (2015)
Abstract 4097: Significance of glypican-1 expression on tumor stromal cells in gastric carcinoma
Authors: Yuichiro Miki, Masakazu Yashiro, Kishu Kitayama, Hiroaki Kasashima, Go Masuda, Naoshi Kubo, Katsunobu Sakurai, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa
Journal: Cancer Research (2016)

Abstract Background: Glypican1 (GPC1) is a cell surface heparan sulfate proteoglycan that acts as a co-receptor for heparin-binding growth factors, and it plays a crucial role in cancer growth. Recently, it has been reported that GPC1 enriched on cancer-derived exosomes, and GPC1-positive exosomes in the circulation was frequently found in the patients with early pancreatic cancer. However role of GPC1-positive exosomes derived from tumor stromal cells remains to be unclear. The aim of this study is to clarify the significance of GPC1 expression on stromal cells in gastric carcinoma. Methods: A total of 597 patients with gastric cancer was enrolled in this study. An anti-GPC1 antibody was used for immunohistochemical staining. GPC1 expression was scored by the intensity of staining and the percentage of positive cells. GPC1 expression on cancer cells or stromal cells was evaluated. The corelation between GPC1 expression and clinicopathological features was statistically analyzed. Results: GPC1 expression on cancer cells was found in 473 (79%) of 597 cases. GPC1 expression on stromal cells was found in 147 (75%) of 597 cases. A Kaplan-Meier survival curve showed that overall survival of patients with GPC1-positive stromal cells was significantly better (log-rank p = 0.0028) than that with GPC1-negative stromal cells (5-year survival rate; 72.5% vs 57.9%, respectively). In contrast, overall survival was not statistically different (log rank p = 0.090) between patients with GPC1-positive tumor cells and GPC1-negative tumor cells (5-year survival rate; 71.8% vs. 64.6%, respectively). GPC1 expression on stromal cells was significantly correlated with T stage, lymph node metastasis, lymphatic vessel invasion, and clinical stage. Conclusions: GPC1 expression on stromal cells was associated with the good prognosis of patients with gastric cancer. GPC1-positive exosomes in stromal cells might be correlated with the progression of gastric cancer. Citation Format: Yuichiro Miki, Masakazu Yashiro, Kishu Kitayama, Hiroaki Kasashima, Go Masuda, Naoshi Kubo, Katsunobu Sakurai, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa. Significance of glypican-1 expression on tumor stromal cells in gastric carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4097.
Targeting KIR Blockade in Multiple Myeloma: Trouble in Checkpoint Paradise?
Authors: Martin Felices, Jeffrey S. Miller
Journal: Clinical Cancer Research (2016)

Findings within the current issue indicate that treatment with IPH2101 when used as a monotherapy in smoldering multiple myeloma, meant to enhance natural killer (NK) cell function through inhibitory KIR blockade, results in a surprising reduction of NK-cell function mediated through monocyte trogocytosis. The significance of these findings is discussed. Clin Cancer Res; 22(21); 5161-3. ©2016 AACRSee related article by Carlsten et al., p. 5211.
Abstract 4548: High throughput siRNA screens uncover a high rate of USP8 and ESCRT pathway dependency in squamous carcinoma cell lines
Authors: Wendy Zhong, Elissa Cosgrove, Elissa Swearingen, Mike Ollmann, Jayee Banerjee, Vivienne Watson, Peter Jaeckel, Mariana Pfreimer, Silvia Materna-Reichelt, Holger Beckmann, Paul Kassner, Astrid Ruefli-Brasse, Olivier Nolan-Stevaux
Journal: Cancer Research (2016)

Abstract USP8 and the ESCRT pathway (endosomal sorting complex required for transport) are required for cellular homeostasis through key functions in shuttling ubiquitinated proteins towards lysosomal degradation, and through regulating the maturation of autophagosomal structures. In large-scale siRNA screens, the vast majority of cancer cell lines do not demonstrate dependency on USP8 or ESCRT pathway components for viability. However, we identified three cell lines (HCC70, HCC1954 and PFSK1) that are acutely dependent on USP8 and other ESCRT components (HGS, TSG101) for viability. Using a transcriptome-wide association approach, we found that these three USP8-dependent cell lines also had in common the expression of SerpinB3, also known as SCCA1 (Squamous Cell Carcinoma Antigen 1). After selecting additional Squamous Cell Carcinoma cell lines for further validation of USP8-dependency by siRNA screening, we found that Squamous Carcinoma cell lines, irrespective of their SerpinB3 expression status, were far more likely to be dependent on USP8 for viability (23%; N = 22) than cancer cell lines of non-Squamous epithelial origin (4.5%; N = 67). To unravel possible molecular mechanisms underpinning the requirement of USP8 for the viability of USP8-dependent Squamous Carcinoma cell lines (including SCABER, BICR22, CALU1 and EBC1), we conducted additional transcriptome association studies and genetic interaction screens to uncover genes that are synthetic lethal with USP8 knock-down. Citation Format: Wendy Zhong, Elissa Cosgrove, Elissa Swearingen, Mike Ollmann, Jayee Banerjee, Vivienne Watson, Peter Jaeckel, Mariana Pfreimer, Silvia Materna-Reichelt, Holger Beckmann, Paul Kassner, Astrid Ruefli-Brasse, Olivier Nolan-Stevaux. High throughput siRNA screens uncover a high rate of USP8 and ESCRT pathway dependency in squamous carcinoma cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4548.
Using Discordance in Monozygotic Twins to Understand Causality of Cardiovascular Disease Risk Factors
Authors: David J. Davidson, Michael H. Davidson
Journal: JAMA Internal Medicine (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 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
Prognostic factors for tumor relapse in seminoma stage I patients: a systematic review.
Authors: Friedemann Zengerling, Frank Kunath, Katrin Jensen, Christian Ruf, Stefanie Schmidt, Annabel Spek
Journal: Journal of Clinical Oncology (2016)

e16057 Background: Many efforts have been made to introduce prognostic factors into decision-making on adjuvant treatment in stage I seminoma. A number of clinical, histopathological and molecular factors have been identified in retrospective analyses. Unfortunately, they lacked validation or were counteracted by conflicting results of follow-up studies. Thus, we systematically summarized the available evidence on prognostic factors for stage I seminoma. Methods: We performed a systematic literature search of Medline, Web of Science, Cochrane library and the ASCO, AUA and EAU conference proceedings. According to our prospectively registered protocol (PROSPERO CRD42014009434; Kunath et al Syst Rev 2015) we identified studies reporting on prognostic factors for tumor relapse in seminoma stage I patients undergoing surveillance with a minimum follow-up of two years. Study screening, data extraction and quality assessment was independently performed by two reviewers. Hazard ratios were extracted to measure the relationship between potential prognostic factors and tumor relapse and a meta-analysis was planned in the case of sufficient homogeneous data. Results: Out of 2555 articles initially reviewed, 14 studies met our inclusion criteria (4 prospective, 9 retrospective, 1 unclear), including 4606 patients. A total of 20 different prognostic factors were identified. Among the most frequently reported factors, tumor size (reported as dichotomous and continuous) was significantly associated with relapse in 7/9 studies, including 4148 evaluable patients (Ʃ). In contrast, rete testis invasion was associated with relapse in only 3/9 studies (Ʃ: 4148 pt.). Lymphovascular invasion (0/8 studies; Ʃ: 4106 pt.), young age at diagnosis (1/7 studies; Ʃ: 4003 pt.) and preoperative HCG level (0/5 studies; Ʃ: 2641 pt.) did not predict tumor relapse. Methodological and clinical data heterogeneity did not allow a meta-analysis. The overall quality of the included studies was moderate to poor according to the risk of bias assessment. Conclusions: Our results emphasize the value of tumor size as a prognostic factor for relapse in patients with stage I seminoma, outperforming other histopathologic factors such as rete testis invasion.
Abstract 3726: Predicting cellular response to small molecule Mcl-1 antagonists
Authors: Leah Hogdal, John Sensintaffar, Allison Arnold, Craig Goodwin, Zhiguo Bian, Subrata Shaw, Chris Tarr, Taekyu Lee, Edward Olejniczak, Stephen Fesik
Journal: Cancer Research (2016)

Abstract Myeloid cell leukemia -1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 protein family which many cancers overexpress and depend on for survival. Mcl-1 inhibits apoptosis by binding to Bax and Bak, inhibiting the effectors of apoptosis from oligomerizing at the outer membrane of the mitochondria to promote cell death. Due to its role in cancer and resistance development to conventional chemotherapies, efforts to potently and specifically target MCL-1 have been ongoing. We have discovered novel small molecule inhibitors that selectively disrupt Mcl-1-Bim binding in the sub-nanomolar range. Anti-proliferative activities of our leading Mcl-1 inhibitors were assessed in a panel of hematological and solid cancer cell lines. We found that our compound promoted apoptosis in a subset of cell lines tested. As there was a variable response, we used BH3 profiling, which is a functional assay that rapidly measures dependence on any of the anti-apoptotic Bcl-2 family proteins for an individual sample to predict in vitro sensitivity to our Mcl-1 antagonists. Using the MS1 peptide, a known potent and selective Mcl-1 binder as a positive control in the BH3 profiling assay, we found a correlation between the BH3 profiling measurement of anti-apoptotic dependence to Mcl-1 and increased cytotoxicity caused by our compounds. These studies demonstrate that our compounds promote apoptosis through a selective inhibition of Mcl-1 mechanism of action and supports further investigation of our compounds in in vivo models of cancer. Citation Format: Leah Hogdal, John Sensintaffar, Allison Arnold, Craig Goodwin, Zhiguo Bian, Subrata Shaw, Chris Tarr, Taekyu Lee, Edward Olejniczak, Stephen Fesik. Predicting cellular response to small molecule Mcl-1 antagonists. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3726.