tbuckley/cabot-search huggingface dataset:
Abstract 4828: Differential gene expression profile of tissue factor pathway inhibitor-2 (TFPI-2) in malignant pleural mesothelioma
Authors: Anil Wali, Ying Wang, Adi Tarca, Fulvio Lonardo, Zhandong Liu, Arun K. Rishi, Harvey I. Pass
Journal: Cancer Research (2015)

Abstract Malignant pleural mesothelioma (MPM) is an asbestos-related malignancy characterized by rapid progressive local growth, late metastases, and poor prognosis despite aggressive strategies involving surgery, chemotherapy, and radiation. The tissue factor pathway inhibitor-2 (TFPI-2) has been shown to play an important role in the regulation of extracellular matrix digestion and remodeling, and its reduced synthesis is implicated in various pathophysiological processes such as inflammation and tumor growth/metastasis. In this study we have elucidated the gene expression profile of TFPI-2 among 22 MPM tumor samples using Affymetrix U133AB chip platform. We noticed 13/22 tumors had more than 3-fold reduction in their TFPI-2 gene expression patterns compared to three normal peritoneums. Decreased TFPI-2 expression was observed in majority of epithelial histotypes that exhibited short-term recurrence (STR &amp;lt;12 months) compared to longer time to relapse (LTR after surgery), group of MPM tumor samples. TFPI-2 expression was profoundly decreased (&amp;gt;4-fold) among 5 out of 7 autologous normal pleura-MPM tumor samples. We also found &amp;gt; 3-fold decreased TFPI-2 gene expression pattern in three out of six MPM patient derived cell lines. A robust 2-fold induction in TFPI-2 gene expression was found as a consequence of 5′-aza-2′-deoxycytidine (5-AzaC) and trichostatin-A combination treatment of two MPM patient derived cell lines. Studies are underway to assess whether TFPI-2 promoter hypermethylation is involved in the down-regulation of its expression pattern seen among fifty percent of MPM tumor samples. Further studies are needed to understand the regulation and interaction of TFPI-2 in mesothelioma carcinogenesis that could be utilized for future early detection and therapeutic strategies to combat this insidious disease. Note: This abstract was not presented at the meeting. Citation Format: Anil Wali, Ying Wang, Adi Tarca, Fulvio Lonardo, Zhandong Liu, Arun K. Rishi, Harvey I. Pass. Differential gene expression profile of tissue factor pathway inhibitor-2 (TFPI-2) in malignant pleural mesothelioma. [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 4828. doi:10.1158/1538-7445.AM2015-4828
Abstract 2119: Identification of a RNA binding protein, SSP1, inducing cell growth in esophageal squamous cell carcinoma (ESCC)through posttranscriptional regulation of target genes
Authors: Issei Imoto, Kiyoshi Masuda, Katsutoshi Shoda, Jyunichi Hamada
Journal: Cancer Research (2015)

Abstract RNA-binding proteins (RBPs) involve in many post-transcriptional aspects of RNA metabolism. Although the impact of RBPs on expression of cancer-associated genes is well recognized, their crucial functions in carcinogenesis remain unclear. Here we show that a RBP, squamous cell carcinoma-specific protein 1 (SSP1, Lab name), promotes the cell growth in esophageal squamous cell carcinoma (ESCC) through regulating the expression of cell cycle- and apoptosis-associated genes. Immunohistochemical analysis of dissected ESCC samples showed that SSP1 was highly expressed in advanced ESCC compared with normal tissues. Expression levels of SSP1 was positively and significantly correlated with tumor size, invasion depth and overall survival of patients with ESCC. The correlation between SSP1 expression level and overall survival was significant even after stratified with other clinicopathological factors, indicating SSP1 to be an independent prognosticator in ESCC. Knockdown of SSP1 inhibited cell growth and induced G0/G1 arrest in ESCC cell lines, whereas stably overexpressed SSP1 promote cell growth. Ribonucleoprotein immunoprecipitation analysis followed by RNA sequencing (RIP-seq) revealed that SSP1 bound to large sets of mRNAs, including TP53, RB1, CCNA2, CCND1, BAX, and FAS, and regulated their expression through regulation their translation. Our results indicated SSP1 might be one of the crucial molecular targets for ESSC. Citation Format: Issei Imoto, Kiyoshi Masuda, Katsutoshi Shoda, Jyunichi Hamada. Identification of a RNA binding protein, SSP1, inducing cell growth in esophageal squamous cell carcinoma (ESCC)through posttranscriptional regulation of target genes. [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 2119. doi:10.1158/1538-7445.AM2015-2119
Long-Term Polyclonal and Stable Gene Transfer into Rhesus Repopulating Hematopoietic Stem Cells Using a Simian Immunodeficiency Virus-Based Lentiviral Vector System.
Authors: Yoo-Jin Kim, Nadia L. Hussein, Peiman Hematti, Bum-Kee Hong, Boris Calmels, Robert E. Donahue, Hideki Hanawa, Arthur W. Nienhuis, Cynthia E. Dunbar
Journal: Blood (2006)
Profile of Chronic Transfusion-Dependent Patients In Spain (20CH Study)
Authors: Raquel de Paz, Ma Carmen Losada Castillo, Matías Díaz Sánchez, Juan García-Talavera, Teresa Pascual García, Teresa Bernal Del Castillo, Rafael Franco Osorio, Pilar Giraldo, Carmen Pedro, Antoni Julià, Andreu Llorente, Ma Luz Martino Galiana, Marta Dueñas Usategui, Manuel Jurado Chacón, Iñigo Romón, Dolores Morales, Concha Zamora De Pedro, Jose Luis Díez, Isabel Sanjuán, Jordi Sierra Gil, Luis Palomera
Journal: Blood (2010)
Optimizing Outcomes for Cutaneous Head and Neck Melanoma
Authors: Karen L. Connolly, Klaus J. Busam, Kishwer S. Nehal
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Presentation of breast cancer (BC) diagnosed at or before 30 years of age: Implications for screening women at hereditary risk.
Authors: P. de Alcantara Filho, T. A. King, E. A. Morris, C. Hudis, M. E. Robson
Journal: Journal of Clinical Oncology (2011)

1526 Background: Women with BRCA1/2 or P53 mutations are recommended BC surveillance with mammogram (MMG) and MRI beginning at age 25. The incremental yield of MMG in this age group is not clear. Methods: The MSK Breast Disease Management Team database was queried to identify women diagnosed with BC =< 30 years. Medical records were abstracted to determine clinical characteristics and mode of presentation. Results: Between 1/99 and 7/08, 345 women with BC diagnosed =< 30 years (median 28, 11-30) were evaluated at our institution before definitive treatment. 269 (78%) were white, 23 (6.6%) black, and 13 (3.8%) Hispanic. Most presented with a palpable mass (324/345, 94%) or nipple discharge (9/345, 2.6%). 6 patients (1.8%) were asymptomatic. Median tumor size was 21.5 mm (1-150). Of those with complete information, 147/301 (48.8%) had axillary nodal metastases, 132/345 (44.1%) were HR+ (ER and/or PR+) and HER2-, 76 (25.4%) were TNBC, 33/345 (11%) were HR-/HER2+, and 58/345 (19.4%) were HR+/HER2+. Diagnostic MMG was suspicious for malignancy in 238/286 (83.2%) women. Diagnostic US was abnormal in 307/335 patients (91.6%). Both MMG and MRI were performed before lesion excision in 89 women. MRI demonstrated the lesion of concern in all cases (100%). Additional ipsilateral or contralateral lesions were noted by MRI in 31 women (34.8%). There were 0/89 (0%, 95% CI 0-4%) that were MMG+/MRI-. There were 20/89 cases (22.5%, 95% CI 15-32%) that were MRI+/MMG-. Conclusions: Women diagnosed with breast cancer at or before the age of 30 tend to present with significant local disease. HER2 overexpression appears to be more common than in unselected breast cancer cases. The sensitivity of diagnostic MMG in women with BC =< 30 years is suboptimal, even in a population presenting with palpable masses and relatively large disease. All cancers in this setting were visualized by MRI, and there were no cases where MMG identified MRI-occult BC. Although these women were not undergoing routine screening, these findings suggest that the incremental value of MMG may be limited in women =< 30 who are undergoing MRI-based BC surveillance.
A Phase I, pharmacokinetic (PK) and pharmacodynamic (PD) study of a novel histone deacetylase inhibitor LAQ824 in patients with hematologic malignancies
Authors: O. G. Ottmann, D. J. Deangelo, R. M. Stone, H. Pfeifer, B. Lowenberg, P. Atadja, B. Peng, J. W. Scott, M. Dugan, P. Sonneveld
Journal: Journal of Clinical Oncology (2004)

3024 Background: LAQ824 is a novel cinnamic acid hydroxamate that inhibits HDAC activity, IC50 of 0.03 μM, and acetylates hsp90 thereby inducing proteosomal degradation of Bcr-Abl and her-2. Methods: LAQ824 is administered by a 3 hr IV infusion on days 1–3 of a 21 day cycle to pts with ALL, AML, CLL, CML in blast crisis or advanced MDS. Modified continuous reassessment method (MCRM) was utilized for dose escalation. Results: 21 pts (median age: 68 yrs; 14 M, 7 F) with AML (15 pts), MDS (4 pts) and CLL (2 pts) have been treated at dose levels (mg/m2): 6 (2 pts); 12 (3 pts); 24 (3 pts); 36 (4 pts); 54 (4 pts); 80 (5 pts). One patient experienced DLT, at the 54 mg/m2 dose level, (cerebral bleed secondary to thrombocytopenia in a CLL patient with rapid disease progression). Grade 2 hyperbilirubinemia was seen in 6 pts. but was rapidly reversible (generally in < 1 week). Monitoring with > 400 ECGs, demonstrates no QTc prolongation. One patient with de novo M1 AML achieved a CR after 2 cycles, and remains in CR after 6 cycles. Six patients had stable disease (5 pts, 4 AML, 1 MDS) or hematologic improvement (1 pt, MDS). PD study for increased histone acetylation (HA) in peripheral lymphocytes was seen on days of dosing ≥ 12 mg/m2, and at ≥ 36 mg/m2 was present for 24 hours after the last dose. PK in 15 pts receiving LAQ824 over a dose range of 6–54 mg/m2 were evaluated by noncompartmental analysis. Plasma LAQ824 concentrations were determined using HPLC/MS/MS assay. Exposure (AUC) increased proportionally with increasing dose. The mean AUCs(0–24) were 165.4 and 1816.8 ng.h/mL, respectively, for 6 and 54 mg/m2 on Day 1. The mean terminal half-lives ranged from 9 to 18 hr. Comparison of AUC between Day 3 and Day 1 indicated a 1.5 fold drug accumulation. Maximum plasma concentrations (Cmax) were observed at 1.5 h after the beginning of infusion, not at the end of infusion, in more than 50% of patients, indicating a non-linear PK. Conclusions: LAQ824 is a novel HDAC inhibitor which is well tolerated, exhibits dose dependent PD effects, and has shown evidence of clinical activity in hematologic malignancies. Further dose escalation is in progress. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceutics Novartis Novartis Novartis
High Readmission Rates Are Associated with a Significant Economic Burden and Poor Outcome in Patients with Grade 3/4 Acute GvHD
Authors: Fiona L Dignan, Michael N Potter, Mark E Ethell, Joy Brennan, Louise McNamara, Stephen O Evans, Claire E. Dearden, Faith E Davies, Gareth J Morgan, Bronwen E. Shaw
Journal: Blood (2011)
STEM-19EGFR EXPRESSION CONFERS STEM CELL-LIKE PROPERTIES TO HUMAN NEURAL PROGENITORS AND GLIOMAS
Authors: Jessica Tome-Garcia, Raymund Yong, Mary Fowkes, Margret Magid, Rut Tejero, Violeta Silva-Vargas, Roland H. Friedel, Fiona Doetsch, Nadejda Tsankova
Journal: Neuro-Oncology (2015)

Activation of the epidermal growth factor receptor (EGFR) pathway is strongly implicated in the proliferation and migration of neural/glial progenitors and gliomas. EGFR is silenced after development but becomes aberrantly overexpressed in many low-grade and most high-grade gliomas, often in the absence of gene-amplification/activating mutations. The phenotype and functional characteristics of EGFR-expressing human brain cells are not well defined, as is the relationship of EGFR expression to gliomagenesis. We recently reported on the selective retention of EGFR expression in adult human subventricular zone (SVZ) glia. Notably, we also showed a strikingly similar epigenetic landscape at the wild-type EGFR promoter between germinal matrix/SVZ and EGFR-expressing gliomas. Here we undertook a detailed characterization of EGFR-expressing cells in the developing and adult human brain using warm postmortem material, and in human glioblastomas after fresh resection, hypothesizing that EGFR-positive cells harbor stem cell-like properties in vitro, which may implicate them in gliomagenesis. To better characterize the phenotype of human EGFR-expressing brain cells in vivo, we performed detailed confocal immunofluorescence analysis with markers for glial/neuronal lineage differentiation and proliferation. We found that during neural development, many EGFR-positive cells co-express markers of oligodendrocyte lineage, such as Olig2, similarly to most glioblastomas. We then analyzed the behavior of these cells in vitro. We used our novel, human-based protocol to isolate cells directly from fresh human samples, taking advantage of the inherent binding affinity of EGFR for its natural ligand, EGF. Intriguingly, we found that EGFR-positive, but not EGFR-negative, cells isolated from germinal matrix and from glioblastomas display stem-cell characteristics in culture, including self-renewal and trilineage differentiation. Our findings suggest that EGFR expression confers stem-cell-like properties to human progenitors and glioma cells, hint that its maintenance may play a role in gliomagenesis, and provide a novel isolation platform of functionally defined EGFR+ glioma populations for further molecular analyses.
Abstract A02: Assessment of germline cancer predisposition genes in 392 unselected pancreatic cancer patients
Authors: Skye McKay, Jeremy Humphris, Amber Johns, Mark Pinese, Ann-Marie Patch, Katia Nones, Sean Grimmond, Andrew Biankin, Nicola Waddell
Journal: Cancer Research (2016)

Abstract Aim: To determine the prevalence of pathogenic germline mutations in known pancreatic cancer (PC) predisposition genes in an unselected PC cohort; identify clinico-pathological characteristics associated with gene carrier status; and analyse somatic genomic data for evidence of biallelic inactivation. Methods: Whole-genome (n = 184) and exome (n = 208) sequencing was performed on matched tumor-normal DNA pairs from 392 predominantly sporadic cases of PC. Pathogenic mutations were assessed in 13 cancer predisposition genes associated with PC risk (APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, TP53. Results: A total of 377 unique high confidence germline variants were observed in the 13 PC predisposition genes. 22 were classified as pathogenic and identified in 23/392 (5.9%) PC patients. The mutations occurred in BRCA2 (n=9), ATM (n=4), BRCA1 (n=3), PALB2 (n=3), CDKN2A (n=2) and one each in PMS2 and STK11. Truncating BRCA2 and PALB2 mutations were detected in 2 cases classified as familial PC. There was no significant difference in average age at diagnosis (67.9 vs 66.6, P = 0.5468), post-resection survival (20.3 vs 20.5 months, P = 0.9788), family history of malignancy (55.6% vs 40.5%, P = 0.2249) or personal history of malignancy (31.8% vs 15.0%, P = 0.0642) between those with and those without a pathogenic germline PC risk mutation. Patients harboring BRCA1, BRCA2 or PALB2 mutations were associated with an increased family history of breast or ovarian cancer (27.3% vs 6.3%, P = 0.0348). The second-hit mechanism could be assessed in tumors with &amp;gt;30% cellularity (n=16), of which 75% (7 BRCA2, 4 ATM, 1 BRCA1) showed evidence of biallelic inactivation. Conclusion: 5.9% of PC patients with predominantly sporadic disease have a pathogenic germline mutation in cancer predisposition genes associated with PC risk. However, carrier status did not significantly affect age at diagnosis, survival, personal or family history of malignancy in this cohort. Second hit mechanisms were identified in 12 (52.2%) cases, supporting a potential role in pancreatic tumorgenesis. An expanded analysis of the germline data is required to further understand the genetic basis of both sporadic and familial PC. Citation Format: Skye McKay, Jeremy Humphris, Amber Johns, Mark Pinese, Ann-Marie Patch, Katia Nones, Australian Pancreatic Cancer Genome Initiative (APGI), Sean Grimmond, Andrew Biankin, Nicola Waddell.{Authors}. Assessment of germline cancer predisposition genes in 392 unselected pancreatic cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A02.
Phase II study of RO4929097 in metastatic colorectal cancer.
Authors: T. Valone, T. J. Yeatman, D. Sullivan, R. D. Kim, K. Almhanna, J. L. Giglia, J. R. Strosberg
Journal: Journal of Clinical Oncology (2011)

e14058 Background: The Notch pathway is activated in colorectal cancer. Downstream signaling is mediated via cleavage of intracellular Notch (ICN) by a γ-secretase complex. Our gene-expression microarray analysis of 205 patients with colorectal cancer demonstrated significant upregulation of the Notch 1 receptor. We therefore conducted a phase II trial of RO4929097, a γ-secretase inhibitor, in patients with advanced, refractory metastatic colorectal cancer. Methods: Patients with metastatic colorectal cancer who had received at least two prior lines of therapy in the metastatic setting were treated with RO4929097 20 mg po daily 3 days on and 4 days off continuously. Radiographic response was assessed every 2 months on therapy. Immunohistochemical analysis of Notch1, ICN, and HES1, a downstream target gene, was performed on paraffin embedded-tissue specimens. The primary endpoint was overall response rate. Secondary endpoints included PFS, OS, and toxicity. Results: 37 patients were enrolled. No objective radiographic responses were observed. The median progression-free survival was 8 weeks and median overall survival was 6 months. Conclusions: RO4929097 is not active as monotherapy using this dose and schedule in patients with metastatic, refractory colorectal cancer.
Platelets Derived From Patients with Myelodysplastic Syndromes (MDS) Show Defective Platelet Aggregation and Integrin aIIbβ3 Receptor (GPIIb/IIIa) Signaling Caused by a Reduced Expression of Proteins Required for Inside-out Signaling.
Authors: Akos G. Czibere, Julia Fröbel, Sonja Hartwig, Ron-Patrick Cadeddu, Matthias Wilk, Ingmar Bruns, Sebastian Büst, Guido Kobbe, Andrea Kündgen, Jürgen Eckel, Stefan Lehr, Rainer Haas
Journal: Blood (2009)
Pharmacoeconomics of Stem Cell Mobilization Using Cyclophosphamide and G-Csf.
Authors: Madan Jagasia, Heidi Chen, Sheri Dixon, Jodene Hume-Rowland, Bipin N. Savani, Anne T. Neff, Kimberely Moyers, Wichai Chinratanalab, Friedrich Schuening
Journal: Blood (2009)
Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer at high risk for the development of peritoneal metastases. A matched case-control study
Authors: D. Baratti, S. Kusamura, F. Pietrantonio, M. Guaglio, R. Berenato, M. Niger, M. Caporale, E. Leo, M. Deraco, F. De Braud
Journal: Annals of Oncology (2015)
Tumorlike Pigmented Villonodular Synovitis With Atypical Location
Authors: Qian Hua, Jianming Ni
Journal: Clinical Nuclear Medicine (2016)

Pigmented villonodular synovitis (PVNS) is a proliferative disorder of unknown etiology that originates from the synovial membranes of joints. Some PVNS lesions have been misdiagnosed as malignancy due to their tumorlike imaging findings. There are few reports of PVNS on nuclear 3-phase bone imaging. However, 3-phase Tc-MDP bone scan can offer additional information about the dynamic flow features of the lesion, which may do help in differential benign and malignant. The present report describes 3-phase bone imaging in a surgically proven case of PVNS with tumorlike appearance and atypical location.
The Effect of Aggressive Versus Standard Lipid Lowering by Atorvastatin on Diabetic Dyslipidemia
Journal: Diabetes Care (2001)

OBJECTIVE—In patients with type 2 diabetes, intensive glucose regulation, although effective for microangiopathy, has not been shown to have unambiguous preventive effects on the occurrence of cardiovascular disease. Patients with diabetes show a characteristic dyslipidemia (high triglyceride level, low HDL cholesterol level). Aggressive reduction of triglycerides might be an effective method to reduce the cardiovascular risk in these patients. RESEARCH DESIGN AND METHODS—A double-blind, placebo-controlled, randomized study to assess the effect of 30 weeks of administration of atorvastatin 10 and 80 mg on plasma triglyceride levels in 217 patients with type 2 diabetes and fasting triglyceride levels between 1.5 and 6.0 mmol/l. RESULTS—Administration of atorvastatin 10 and 80 mg resulted in significant reductions (25 and 35%, respectively) of plasma triglyceride levels (both P &amp;lt; 0.001). The difference between 10 and 80 mg was not statistically significant (P &amp;gt; 0.5). Atorvastatin 10 mg provided significant reductions from baseline in total cholesterol (−30%, P &amp;lt; 0.001), LDL cholesterol (−40%, P &amp;lt; 0.001), and apolipoprotein B (−31%, P &amp;lt; 0.001), and significantly increased HDL cholesterol from baseline by 6% (P &amp;lt; 0.005). Atorvastatin 80 mg had a similar effect on HDL cholesterol (+5.2%, P &amp;lt; 0.005) but significantly decreased total cholesterol (−40%, P &amp;lt; 0.001), LDL cholesterol (−52%, P &amp;lt; 0.001), and apolipoprotein B (−40%, P &amp;lt; 0.001) more than atorvastatin 10 mg (P &amp;lt; 0.005). The side effects of atorvastatin 10 and 80 mg were similar and did not differ from the patients receiving placebo. CONCLUSIONS—Administration of 10- and 80-mg doses of atorvastatin provides similar, significant reductions from baseline in triglyceride levels in patients with type 2 diabetes. A higher dose of atorvastatin improves cholesterol-related parameters. Both doses were well tolerated in this patient population.