tbuckley/cabot-search huggingface dataset:
Glucocorticoid Receptor Signaling Activates TEAD4 to Promote Breast Cancer Progression
Authors: Lingli He, Liang Yuan, Yang Sun, Pingyang Wang, Hailin Zhang, Xue Feng, Zuoyun Wang, Wenxiang Zhang, Chuanyu Yang, Yi Arial Zeng, Yun Zhao, Ceshi Chen, Lei Zhang
Journal: Cancer Research (2019)

The Hippo pathway plays a critical role in cell growth and tumorigenesis. The activity of TEA domain transcription factor 4 (TEAD4) determines the output of Hippo signaling; however, the regulation and function of TEAD4 has not been explored extensively. Here, we identified glucocorticoids (GC) as novel activators of TEAD4. GC treatment facilitated glucocorticoid receptor (GR)-dependent nuclear accumulation and transcriptional activation of TEAD4. TEAD4 positively correlated with GR expression in human breast cancer, and high expression of TEAD4 predicted poor survival of patients with breast cancer. Mechanistically, GC activation promoted GR interaction with TEAD4, forming a complex that was recruited to the TEAD4 promoter to boost its own expression. Functionally, the activation of TEAD4 by GC promoted breast cancer stem cells maintenance, cell survival, metastasis, and chemoresistance both in vitro and in vivo. Pharmacologic inhibition of TEAD4 inhibited GC-induced breast cancer chemoresistance. In conclusion, our study reveals a novel regulation and functional role of TEAD4 in breast cancer and proposes a potential new strategy for breast cancer therapy. SIGNIFICANCE: This study provides new insight into the role of glucocorticoid signaling in breast cancer, with potential for clinical translation.
Micronodules Detected on Computed Tomography During the National Lung Screening Trial: Prevalence and Relation to Positive Studies and Lung Cancer
Authors: Reginald F. Munden, Caroline Chiles, Phillip M. Boiselle, JoRean D. Sicks, Denise R. Aberle, Constantine A. Gatsonis
Journal: Journal of Thoracic Oncology (2019)

IntroductionIn the National Lung Screening Trial (NLST) all cases with a 4-mm nodule (micronodule) and no other findings were classified as a negative study. The prevalence and malignant potential of micronodules in the NLST is evaluated to understand if this classification was appropriate.Methods and MaterialsIn the NLST a total of 53,452 participants were enrolled with 26,722 undergoing low-dose computed tomography (CT) screening. To determine whether a micronodule developed into a lung cancer, a list from the NLST database of those participants who developed lung cancer and had a micronodule recorded was selected. The CT images of this subset were reviewed by experienced, fellowship-trained thoracic radiologists (R.F.M., C.C., P.M.B., and D.R.A.), all of whom participated as readers in the NLST.ResultsThere were 26,722 participants who underwent CT in the NLST, of which 11,326 (42%) participants had at least one CT with a micronodule. Five thousand five hundred sixty (49%) of these participants had at least one positive CT examination, of which 409 (3.6%) subsequently were diagnosed with lung cancer. Of the 409 lung cancer cases with a micronodule recorded, there were 13 cases in which a micronodule developed into lung cancer. Considering the 13 cases, they represent 1.2% (13 of 1089) of the lung cancers diagnosed in the CT arm of the NLST and 0.11% (13 of 11,326) of the total micronodule cases. Additionally they represent 0.23% (13 of 5560) of the micronodule and at least one positive CT examination cases and 3.2% (13 of 409) of the micronodule cases diagnosed with lung cancer. The average size of the nodule at baseline (recorded as maximum diameter by perpendicular diameter) was 3.0 × 2.5 mm (ranges 2 x 4 mm and 2 x 4 mm) and at the positive CT the nodule was 11.1 × 8.6 mm (ranges, 6 x 20 mm and 5 x 14 mm); a difference of average change in size of 8.1 × 6.1 mm. The average number of days from first CT with a micronodule recorded to positive CT was 459 days (range, 338 – 723 days), the mean time from first CT with micronodule to lung cancer diagnosis was 617 days (range, 380 – 1140 days) and the mean time from positive CT to lung cancer diagnosis was 160 days (range, 18 – 417 days). Histologically, there was one small cell carcinoma and 12 non–small cell with stages of IA in 8 (62%), stage IB in 2 (15%), and 1 each stage IIIA, IIIB, and IV. The overall survival of NSCLC cases with a micronodule was not significantly different than the survival of the CT subset diagnosed with NSCL (p = 0.36).ConclusionsMicronodules are common among lung cancer–screened participants and are capable of developing into lung cancer; however, following micronodules by annual CT screening surveillance is appropriate and does not impact overall survival or outcome.
Where to look for sentinel node in breast cancer?
Authors: Anton J. Scharl, Andreas Düran
Journal: Journal of Clinical Oncology (2012)

2560 Background: It has been observed, that the caudal Axilla on the border to pectoralis muscle is predicive for the sentinel node. The sono-morphology of lymph nodes has been the subject of multiple publications, usually dealing with malignant melanoma. In the context of sentinel lymph node biopsy (SLNB) in breast cancer patients, the following study examines the feasibility of the sonographic differentiation of the Sentinel lymph node (SLN) from neighboring non-SLNs and whether sentinel-ultrasound-needle localization (SUN) is a useful addition or alternative to current methods of “lymphatic mapping”. Methods: During a prospective study performed from 1/2003 to 9/2005 including 404 breast cancer patients (Tis-T4), the SLNB was performed using patent blue+/- 99Tc-Nanocoll. In addition to and independent of this method, the axilla was sonographically examined for “reactive” lymph nodes n=180 pt. (Siemens Elegra 7.5 MHz). The “reactivity” of the nodes was quantified using an index , which allowed the comparison of adjacent nodes. The most “reactive” lymph node in the caudal axilla was identified as the “Ultrasound-Sentinel-Node”(US-SLN) and has been marked with a wire. Results: In 180 patients the SLN was localized using the standard methods as well as (SUN). The was no difference in detection rates of US-SLN and the standard methods in tumor-free nodes(SLN-). However, for patients with axillary metastases (SLN+) SUN provided superior detection rate (99,1%). The false-negative-rate was reduced from 10,7 % to 1,3%. This was attributed to the embolization of lymph vessels afferent to the metastasized (SLN+) node causing a bypass of the “lymphatic mapping” and inhibiting detection. Conclusions: The SUN–Method is comparable to “lymphatic mapping” in tumor free nodes (SLN -). If SLN is metastasized (SLN+) - SUN is superior to the standard methods in sensitivity and specificity (80%) and the false-negative-rate can be reduced. Systematic axilla sonography is an effective method for the SLN-Localisation, and offers an excellent method for quality control during SLNB.
Prognostic significance of radiologic features of pneumonitis induced by anti-PD-1 therapy.
Authors: Satoshi Watanabe, Takeshi Ota, Masachika Hayashi, Hiroyuki Ishikawa, Takao Miyabayashi, Masaki Terada, Kazuhiro Sato, Takashi Ishida, Hiroshi Tanaka, Akira Iwashima, Satoshi Shoji, Koichiro Nozaki, Kosuke Ichikawa, Rie Kondo, Hirohisa Yoshizawa, Toshiaki Kikuchi
Journal: Journal of Clinical Oncology (2019)

9065 Background: Anti-PD-1 therapy is now a standard treatment for patients with NSCLCs. Pneumonitis induced by immune-check point inhibitors is potentially fatal; however, some studies have shown that antitumor effects were enhanced in patients with pneumonitis. Although several radiologic patterns of pneumonitis induced by anti-PD-1 therapy have been reported, the association between radiologic features and clinical outcomes, especially enhancement of antitumor effects remains unclear. Methods: We retrospectively evaluated data of NSCLC patients treated in 1 st to 3 rd line with anti-PD-1 antibodies (nivolumab or pembrolizumab) at Niigata Lung Cancer Treatment Group. Pneumonitis was diagnosed by the treating investigators. The chest CT scans of patients with pneumonitis were independently reviewed by one radiologist and two pulmonologists to classify pneumonitis into 5 subtypes: cryptogenic organizing pneumonia-like (COP), ground glass opacities (GGO), interstitial, hypersensitivity and pneumonitis not otherwise specified (NOS). Results: Of 231 patients who received anti-PD-1 antibodies, pneumonitis developed in 33 patients (14.3%) at 7 institutions between January 2016 to October 2017. Of 33 patients with pneumonitis, the median age was 66 (range 45 to 82 years), 7 were female, 25 received nivolumab, and 8 received pembrolizumab. Sixteen patients were classified as GGO, 16 patients had COP-like appearance and one patient had NOS. The median survival time was significantly longer among patients with COP than among those with GGO (not reached vs. 7.8 months; HR 0.29, 95% CI 0.09-0.81; p = 0.0071). Pneumonitis improved in 94% (31 of 33) of cases, and one patient died from pneumonitis. The overall response ratio (CR+PR) was 44% in patients with COP and 31% in patients with GGO (p = 0.47). There was no statistical difference in OS between patients with systemic corticosteroid therapy for pneumonitis and those without (not reached vs. 14.8 months; HR 1.4, 95% CI 0.52-4.1; p = 0.51). Conclusions: Patients with pneumonitis classified as COP had significantly longer survival time than those with pneumonitis classified as GGO. Radiologic features of pneumonitis may reflect clinical outcomes after anti-PD-1 therapy.
18F-FDG PET/MR in an Atypical Pediatric Solid Pseudopapillary Pancreatic Tumor
Authors: Annachiara Cavaliere, Chiara Giraudo, Monica Zuliani, Diego Cecchin, Emilio Quaia
Journal: Clinical Nuclear Medicine (2019)

Abstract MR and 18 F-FDG PET/MR images of a 15-year-old boy with recurrent mild abdominal pain and hyperamylasemia demonstrating a pancreatic head lesion hypointense on the T1-weighted and slightly hyperintense on the T2-weighted images, with very small pseudocystic areas, restricted diffusion on the apparent diffusion coefficient map, and focal FDG uptake. No other pathologic findings such as enlarged lymph nodes, vascular invasion, metastases, dilatation of the main pancreatic duct, or pathologic uptake of the parotid glands were detected. The MR features, even if atypical, together with the focal uptake, allowed the diagnosis of pediatric solid pseudopapillary pancreatic tumor, which was then confirmed by histology.
Dynamic contrast-enhanced MRI versus 18F-misonidazol-PET/CT to predict pathologic response in bevacizumab-based neoadjuvant therapy in breast cancer.
Authors: Jesus Garcia-Foncillas, Purificación Martinez, Ainhara Lahuerta, Antonio Llombart Cussac, Maria Garcia Gonzalez, Rosa Maria Sanchez Gomez, Isabel Alvarez, Antonio Anton, Jose J. Illarramendi, Ana De Juan, Elena Galve Calvo, Arrate Plazaola, Serafin Morales, Blanca Hernando, Juan Lao, Valentina Boni, Teresa Puertolas, Stefan Sherer, Gemma Palacios, Jose Manuel Lopez-Vega
Journal: Journal of Clinical Oncology (2012)

10512 Background: To investigate the role of DCE-MRI versus 18F-Misonidazole (FMISO) positron emission tomography (PET/CT) in the prediction of pathological response to bevacizumab-based neodajuvant therapy. Methods: 73 chemotherapy naïve, stage II and III breast cancer (BC) patients (pts) were enrolled in a phase II, single-arm, multicenter, open-label and prospective clinical trial. Pts received single infusion of bevacizumab (15 mg/ kg) (C1) 3 weeks prior to the beginning of neoadjuvant chemotherapy (NAC) consisting of 4 cycles of docetaxel (60 mg/mq), doxorubicin (50 mg/mq) and bevacizumab (15 mg/ kg) every 21 days (C2-C5), followed by surgery. Tumor proliferation, hypoxia and perfusion were evaluated respectively using 18F-Fluorothymidine (FLT) and 18F-Misonidazole (FMISO) positron emission tomography (PET/CT) and dynamic contrast enhancement magnetic resonance (DCE-MR). Serial imaging studies were performed in parallel at several time points including baseline (BL) and 14-21 days after bevacizumab alone (C1). Results: After only one administration of bev, tumor proliferation and perfusion assessed using FLT-PET and DCE-MRI significantly decrease (-26% and -46%, p&lt;0.001) but these changes were not found to be associated with final response. Most important, changes in tumor hypoxia induced by bevacizumab was significantly associated with pathological response (p= 0.004) and was an independent predictor of response in multivariate analysis (RR=0.95, IC 95% 0.92-0.99, p=0.02). Decrease in FMISO uptake &gt;10% yielded a ROC curve area of 0.7 (95% CI: 0.56 - 0.85) with high specificity (94%). Conclusions: Our findings suggest a significant value of early changes in tumor hypoxia assessed by FMISO-PET as a biomarker of pathological response in bevacizumab-based neoadjuvant therapy in breast cancer.
Widespread Translational Control of Fibrosis in the Human Heart by RNA-Binding Proteins
Authors: Sonia Chothani, Sebastian Schäfer, Eleonora Adami, Sivakumar Viswanathan, Anissa A. Widjaja, Sarah R. Langley, Jessie Tan, Mao Wang, Nicholas M. Quaife, Chee Jian Pua, Giuseppe D’Agostino, Shamini Guna Shekeran, Benjamin L. George, Stella Lim, Elaine Yiqun Cao, Sebastiaan van Heesch, Franziska Witte, Leanne E. Felkin, Eleni G. Christodoulou, Jinrui Dong, Susanne Blachut, Giannino Patone, Paul J.R. Barton, Norbert Hubner, Stuart A. Cook, Owen J.L. Rackham
Journal: Circulation (2019)

Fibrosis is a common pathology in many cardiac disorders and is driven by the activation of resident fibroblasts. The global posttranscriptional mechanisms underlying fibroblast-to-myofibroblast conversion in the heart have not been explored.Genome-wide changes of RNA transcription and translation during human cardiac fibroblast activation were monitored with RNA sequencing and ribosome profiling. We then used RNA-binding protein-based analyses to identify translational regulators of fibrogenic genes. The integration with cardiac ribosome occupancy levels of 30 dilated cardiomyopathy patients demonstrates that these posttranscriptional mechanisms are also active in the diseased fibrotic human heart.We generated nucleotide-resolution translatome data during the transforming growth factor β1-driven cellular transition of human cardiac fibroblasts to myofibroblasts. This identified dynamic changes of RNA transcription and translation at several time points during the fibrotic response, revealing transient and early-responder genes. Remarkably, about one-third of all changes in gene expression in activated fibroblasts are subject to translational regulation, and dynamic variation in ribosome occupancy affects protein abundance independent of RNA levels. Targets of RNA-binding proteins were strongly enriched in posttranscriptionally regulated genes, suggesting genes such as MBNL2 can act as translational activators or repressors. Ribosome occupancy in the hearts of patients with dilated cardiomyopathy suggested the same posttranscriptional regulatory network was underlying cardiac fibrosis. Key network hubs include RNA-binding proteins such as Pumilio RNA binding family member 2 (PUM2) and Quaking (QKI) that work in concert to regulate the translation of target transcripts in human diseased hearts. Furthermore, silencing of both PUM2 and QKI inhibits the transition of fibroblasts toward profibrotic myofibroblasts in response to transforming growth factor β1.We reveal widespread translational effects of transforming growth factor β1 and define novel posttranscriptional regulatory networks that control the fibroblast-to-myofibroblast transition. These networks are active in human heart disease, and silencing of hub genes limits fibroblast activation. Our findings show the central importance of translational control in fibrosis and highlight novel pathogenic mechanisms in heart failure.
Extracellular fluid volume is associated with incident end-stage kidney disease and mortality in patients with chronic kidney disease
Authors: Anne-Laure Faucon, Martin Flamant, Marie Metzger, Jean-Jacques Boffa, Jean-Philippe Haymann, Pascal Houillier, Eric Thervet, François Vrtovsnik, Bénédicte Stengel, Guillaume Geri, Emmanuelle Vidal-Petiot, François Vrtovsnik, Eric Daugas, Nahid Tabibzadeh, Martin Flamant, Emmanuelle Vidal-Petiot, Alexandre Karras, Stéphane Roueff, Eric Thervet, Pascal Houillier, Marie Courbebaisse, Caroline Prot-Bertoye, Jean-Philippe Bertocchio, Gérard Maruani, Jean-Jacques Boffa, Pierre Ronco, Hafedh Fessi, Eric Rondeau, Marine Livrozet, Emmanuel Letavernier, Jean-Philippe Haymann, Marie Metzger, Pablo Urena-Torres, Bénédicte Stengel
Journal: Kidney International (2019)
18F-FDOPA PET Compared With 123I-Metaiodobenzylguanidine Scintigraphy and 18F-FDG PET in Secreting Sporadic Pheochromocytoma
Authors: Alexandre Lugat, Delphine Drui, Eric Mirallié, Françoise Kraeber-Bodéré, Catherine Ansquer
Journal: Clinical Nuclear Medicine (2019)

Abstract We report the case of a 23-year-old man presenting a right hypersecreting pheochromocytoma, falsely negative on 18 F-FDG PET/CT and on 123 I-metaiodobenzylguanidine ( 123 I-MIBG) scintigraphy but strongly positive on 18 F-FDOPA PET/CT. Functional imaging has a key role in diagnosis and prognosis of pheochromocytomas, but choosing the most relevant modality remains difficult. Despite its high specificity, 123 I-MIBG has a limited sensitivity. 18 F-FDG can be used, but it is an unspecific tracer, and 18 F-FDG uptake in brown adipose tissue can hinder the analysis. However, 18 F-FDOPA shows very high sensitivity and specificity in pheochromocytomas with fewer drug interferences than 123 I-MIBG.
Sepsis deaths decrease in hospitals with mandatory treatment protocols, US study finds
Authors: Susan Mayor
Journal: BMJ (2019)

Death rates from sepsis in New York state fell more quickly than in other states after a state wide mandatory treatment protocol was introduced, a study has shown.

The retrospective study examined more than a million admissions to hospital of people with sepsis to evaluate the effect of New York state’s regulations.

“Rarely in the US do we force hospitals to implement specific clinical protocols,” said the lead author, Jeremy Kahn, from the University of Pittsburgh. “For the first time, state officials are enshrining in regulations that hospitals must follow certain evidence based protocols when it comes to sepsis. …
Role of Rotavirus Vaccination in Decline in Incidence of Type 1 Diabetes
Authors: Joachim Rosenbauer, Katty Castillo, Christina Bächle
Journal: JAMA Pediatrics (2019)

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
Prognostic and predictive factors associated with ipilimumab related adverse events: A retrospective analysis of 11 NCI sponsored ipilimumab phase I clinical trials.
Authors: Aman Chauhan, Tanvir Kabir, Jianrong Wu, Jing Wei, Charles Kunos
Journal: Journal of Clinical Oncology (2019)

86 Background: We review factors affecting ipilimumab (ipi) associated toxicity in various NCI sponsored phase I clinical trials. Methods: NCI database for NCI sponsored phase I clinical trials evaluating ipilimumab was queried for adverse effects, radiological response data, lymphocyte counts, LDH, albumin, ECOG performance status, duration of treatment and diagnosis. Only treatment related AEs were analyzed. Events repeating across consecutive cycles were treated as a single event. Duration of treatment was calculated starting from cycle 1 day 1 of the treatment. IRB approval from NCI was obtained prior to the study. Results: Data from 373 patients from 11 phase I ipilimumab clinical trials were available for analysis. Median age of the study cohort was 55 years. 68%(n = 235) were males. Number of grade 3 and 4 AEs were associated with better radiological response. Mean grade 3 and 4 AEs in CR+PR cohort was 1.167 vs 0.645 in non-responder cohort (p = 0.001). No significant differences in low or high grade AEs were noticed in study cohorts differentiated based on ECOG PS (0 vs 1/2). ECOG PS 3/4 were not included in clinical trials. Pretreatment lymphocyte count, LDH or albumin was not predictive of increased ipilimumab associated toxicity. Ipilumumab associated grade 3 and 4 toxicity was directly associated with the number of concurrently used study agents. Mean grade 3 and 4 AEs were as follows in following cohorts: ipi alone; 0.631 vs ipi+ 1 drug; 0.877 vs ipi+ 2 drugs; 1.408 (p &lt; 0.0136). Number of low grade (grade 1 and 2) toxicity was associated with duration of treatment. r = 0.456 (p &lt; 0.0001). Number of high grade (grade 3 and 4) toxicity was not associated with duration of treatment with ipilimumab. r = 0.032 (p = 0.546). Conclusions: Ipilimumab associated grade 3 and 4 toxicity predicts response to therapy and is associated with higher CR/PR. ECOG PS, pretreatment lymphocyte count, LDH and albumin levels are not associated with ipilimumab toxicity. Lastly, addition of antitumor agents to ipilimumab has potential to cause a significant increase in serious AE’s.
Multi-color imaging of angiogenesis of orthotopic human tumors in the nestin-driven GFP nude mouse
Authors: Yasuyuki Amoh, Lingna Li, Meng Yang, Kensei Katsuoka, A. R. Moossa, Robert M. Hoffman
Journal: Cancer Research (2005)

3838  We have recently shown that the neural-stem cell marker nestin is expressed in hair follicle stem cells and an intrafollicular vessel network in the skin of transgenic mice with nestin-driven green fluorescent protein (ND-GFP) (1, 2). These transgenic mice also express ND-GFP in areas of the brain and the pancreas. The ND-GFP gene was crossed into nude mice on the C57/B6 background. The ND-GFP nude mice were used in the present study to visualize angiogenesis of transplanted human tumors. The human tumors were transplanted into the skin or the pancreas where ND-GFP is expressed in newly formed blood vessels. Human tumors transplanted subcutaneously in the ND-GFP nude mice, including fibrosarcoma, lung cancer, and melanoma, were visualized by their expression of red fluorescent protein (RFP). ND-GFP-expressing blood vessels were visualized under dual-color fluorescence vascularizing the RFP-expressing tumors. An RFP-expressing human pancreas tumor was transplanted to the pancreas of the ND-GFP mice. The ND-GFP cells of the pancreas formed blood vessels which were visualized under dual-color fluorescence to vascularize the RFP-expressing human pancreas tumor. The ND-GFP-expressing blood vessels in the skin and the pancreas were shown to also express the endothelial marker CD31. The ND-GFP nude mice implanted with RFP-expressing tumors enables nascent angiogenesis to be visualized in these tumors by dual-color fluorescence. This model should prove to be useful to study both the mechanism of tumor angiogenesis and for the screening of agents which specifically inhibit this process. (1) Amoh, Y., Hoffman, R.M. et al. Nascent blood vessels in the skin arise from nestin-expressing hair-follicle cells. Proc. Natl. Acad. Sci. USA 101, 13291-13295, 2004. (2) Li, L., Hoffman, R.M. et al. Nestin expression in hair follicle sheath progenitor cells. Proc. Natl. Acad. Sci. USA 100, 9658-9662, 2003.