tbuckley/cabot-search huggingface dataset:
EXTH-20. TARGETING GLIOBLASTOMA METABOLISM THROUGH mTOR AND MITOCHONDRIAL INHIBITION
Authors: Toni Rose Jue, Sylvia Chung, Robert Rapkins, Pierre Dilda, Philip Hogg, Kerrie McDonald
Journal: Neuro-Oncology (2016)

PENAO is a potent mitochondrial inhibitor, currently in a Phase 1 clinical trial in Australia as a pan-cancer treatment. Temsirolimus is an inhibitor of the mTOR pathway, a pathway that is highly upregulated in glioblastoma, and has also been shown to interfere with mitochondrial metabolism. The aim of this study is to combine both PENAO and temsirolimus, both potent inhibitors of mitochondrial metabolism, to synergistically impede glioblastoma growth, particularly in patients with an unmethylated MGMT promoter. PENAO and temsirolimus were tested in vitro as single agents and in combination using patient-derived cell lines (PDCLs). Additionally, in an orthotopic mouse model in which the animals were implanted with the PDCL RN1, we combined PENAO (3 mg/kg/day) and temsirolimus (1 mg/kg/day or 5 mg/kg/day). In vitro drug cytotoxic assays using a panel of PDCLs showed promising synergistic effects with PENAO and temsirolimus. IC50 dose of PENAO and temsirolimus combined showed 11- to 20-fold decrease in cell viability. Annexin V-PI assay revealed that the drug combination induced apoptosis in ~90% of the cell population. Unfortunately, in vivo results showed no significant difference between treatment and control groups, and did not extend survival. Although the combination of PENAO and temsirolimus was highly effective in PDCLs in vitro, it did not translate into a significant survival improvement in vivo. Ongoing studies have identified that the concentration levels of PENAO reaching the brain were inadequate to deliver the synergistic effects observed in vitro. Future studies will investigate mechanisms of enhancing drug delivery of PENAO to the brain and mimic the synergistic effect we observed in vitro.
CBIO-18. HAPLOINSUFFICIENCY OF THE REGULATOR OF THE MUTANT TERT PROMOTER REVERSES GLIOBLASTOMA REPLICATIVE IMMORTALITY
Authors: Andrew Mancini, Ana Xavier-Magalhaes, Wendy Woods, Josie Hayes, Michael Gapinske, Andrew McKinney, Robert Bell, Kyle Walsh, Bruno Costa, Jun Song, Pablo Perez-Pinera, Joseph Costello
Journal: Neuro-Oncology (2016)

Reactivation of telomerase reverse transcriptase (TERT) expression enables cells to overcome replicative senescence and escape telomere dysfunction-induced cell death, fundamental steps in the initiation of human cancer. Over fifty cancer types, including up to 83% of glioblastomas (GBM), 75% of oligodendrogliomas, and 30% of medulloblastomas, harbor activating TERT promoter mutations that are sufficient to enable replicative immortality. Both the C228T and C250T TERT promoter mutations create a binding site that recruits the multimeric ETS factor GABP to the mutant TERT promoter to activate TERT transcription. GABP recruitment occurs across multiple types of cancer with TERT promoter mutations, suggesting a shared mechanism. While GABP can act as a heterodimer or as a heterotetramer, depending on the number of GABP binding sites at the specific locus, only the GABP heterodimer is necessary for normal cell function. Due to the presence of an endogenous GABP binding site in the TERT promoter, we hypothesized that the mutant TERT promoter recruits the GABP heterotetramer to activate TERT transcription in GBM. We further hypothesized that targeting the GABP heterotetramer may be a viable strategy to reverse replicative immortality in GBM. Using CRISPR/Cas9 editing to heterozygously knock out GABPβ1L, the tetramer-forming isoform of GABP, we identify the GABP tetramer as necessary for the activation of the mutant TERT promoter. We demonstrate that GABPβ1L haploinsufficiency reverses replicative immortality in GBM, leading to widespread telomere dysfunction and loss of cellular viability only in TERT promoter mutant cancer cells. These data suggest inhibition of the GABP heterotetramer as a viable therapeutic strategy in TERT promoter mutant GBM and possibly many other cancers.
Reduced Intensity Allogeneic Peripheral Blood Stem Cell Transplantation in Renal Cell Carcinoma: The EIO Experience.
Authors: Rocco Pastano, Daniele Laszlo, Giovanna Andreola, Federica Gigli, Cristina Rabascio, Valentina Raia, Manuela Cazzanti, Fedro Peccatori, Giovanni Martinelli
Journal: Blood (2005)
Insufficient Evidence of Cimetidine Benefit in Protoporphyria—Reply
Authors: Joyce M. C. Teng, Joanna H. Tu
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
Role of Lesional BCL6hiPD-1hi T Follicular Helper Cells As a Cardinal B-Cell Helper to Produce IgG4 in IgG4-Related Disease
Authors: Ryuta Kamekura, Kenichi Takano, Motohisa Yamamoto, Koji Kawata, Sumito Jitsukawa, Tomonori Nagaya, Fumie Ito, Chieko Tsubomatsu, Hiroki Takahashi, Tetsuo Himi, Shingo Ichimiya
Journal: Journal of Allergy and Clinical Immunology (2017)
The Effect of Protein Methylation on Binding of IgE to Profilins Bet v 2, Art v 4 and Amb a 8.
Authors: Krzysztof Kowal, Agnieszka Pampuch, Ewa Sacharzewska, Pawel Bielecki, Caleb Schlachter, Lesa R. Offermann, Maksymilian Chruszcz
Journal: Journal of Allergy and Clinical Immunology (2017)
EZH2 expression and correlation with Ki-67 and p53 in head and neck squamous cell carcinoma
Authors: J. Choi, M. Ahn, Y. Park, Y. Oh, K. Park, H. Jeong, Y. Son, C. Baek, Y. Ahn
Journal: Journal of Clinical Oncology (2009)

e17018 Background: Polycomb group proteins are transcriptional repressors that silence specific sets of genes through chromatin modification. The enhancer of zeste homolog 2 (EZH2), considered a member of the polycomb group proteins, is overexpressed in aggressive forms of several malignancies. However, the role of EZH2 expression in head and neck cancer has not yet been fully determined. This study was conducted to investigate the clinical value of EZH2 expression in head and neck cancer and its correlation with Ki-67 and p53 expression. Methods: Expression of EZH2, Ki-67, and p53 was determined by immunohistochemical staining of tissue microarrays from specimens of 138 cases of head and neck squamous cell carcinoma. Results: High EZH2 expression was observed in 51.5%. 44.2% were positive for p53. The percentage of Ki-67 staining was significantly greater in the EZH2 positive group (12.37 ± 8.51) than in the EZH2 negative group (4.73 ± 6.06, p &lt; 0.001). EZH2 expression was significantly correlated with p53 expression (p = 0.003) and smoking history (p = 0.021). However, we found no significant differences in other clinicopathological parameters (age, sex, primary tumor size, and lymph node metastasis) and survival between the EZH2 positive and negative groups. Conclusions: These results suggest that high EZH2 expression may be associated with tumor cell proliferation and cell cycle regulation in head and neck cancer. No significant financial relationships to disclose.
Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease
Authors: Annelie Falkevall, Annika Mehlem, Isolde Palombo, Benjamin Heller Sahlgren, Lwaki Ebarasi, Liqun He, A. Jimmy Ytterberg, Hannes Olauson, Jonas Axelsson, Birgitta Sundelin, Jaakko Patrakka, Pierre Scotney, Andrew Nash, Ulf Eriksson
Journal: Cell Metabolism (2017)
Similar Efficacy and Pharmacokinetic Behavior of Intravenous Immunoglobulin (Privigen®) in Primary and Secondary Immunodeficiency
Authors: Mikhail Rojavin, John-Philip Lawo, Jeanine Jochems, Shilpa Puli, Jutta Hofmann, Dietmar Pfruender, Michael Tortorici
Journal: Journal of Allergy and Clinical Immunology (2017)
Treatment of Asthmatic Patients with Fluticasone Propionate and Fluticasone Propionate/Salmeterol Multidose Dry Powder Inhalers Compared with Placebo: Patient-Reported Outcomes and Quality of Life
Authors: Lawrence Sher, Gloria Yiu, Anat Sakov, Siyu Liu, Cynthia Caracta
Journal: Journal of Allergy and Clinical Immunology (2017)

This study evaluated patient-reported outcomes in asthmatic patients treated with fluticasone propionate (Fp) and fluticasone propionate/salmeterol (FS) delivered via a novel multidose dry powder inhaler (MDPI). This phase 3, double-blind, parallel-group study (FSS-AS-30017; NCT02141854) evaluated asthmatic patients (ages ≥12 years) previously taking inhaled corticosteroids (ICS) or ICS/long-acting beta2 agonists. After a 14- to 21-day run-in during which rescue medications were replaced with albuterol/salbutamol hydrofluoroalkane metered-dose inhalers and controller medications with Fp MDPI 50 mcg twice daily (BID), patients randomly received Fp MDPI 100 mcg, Fp MDPI 200 mcg, FS MDPI 100/12.5 mcg, FS MDPI 200/12.5 mcg, or placebo MDPI BID for 12 weeks. The efficacy and safety outcomes were previously reported. Patient-reported outcomes including asthma symptoms, rescue medication use, Asthma Quality of Life Questionnaire (AQLQ) scores (patients ≥18 years), and adverse events are reported. The full analysis and safety populations included 720 and 723 patients, respectively. All active treatments significantly improved weekly average total daily asthma symptom scores (p<0.05) and significantly decreased weekly average total daily rescue medication use (p<0.05) compared with placebo over 12 weeks. Improvements in AQLQ from baseline to endpoint were significantly greater for all active treatments versus placebo (p<0.05). Changes from baseline in AQLQ scores achieved the minimal important difference (≥0.5) in both FS MDPI groups. FS MDPI and Fp MDPI were safe and well tolerated. Fp MDPI and FS MDPI significantly improved patient-reported outcomes and quality of life.
Age-Related Differences in B-Cell Inflammatory Responses in Nasal Polyps
Authors: Ara Jo, Jianjun Chen, Richard F. Lockey, Lydia A. Suh, Roderick G. Carter, David B. Conley, Robert C. Kern, Bruce K. Tan, Anju T. Peters, Leslie C. Grammer, Robert P. Schleimer, Seong Ho Cho
Journal: Journal of Allergy and Clinical Immunology (2017)
Predictive Value of Interim 18f-FDG PET-CT Scans on Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Study of Chinese Southwest Oncology Group (CSWOG)
Authors: He Huang, Jia Tian Lin, Chengcheng Guo, Huangming Hong, Raj Shrestha Prem, Xueying Li, Mengping Zhang, Shanshan Li, Xiaojie Fang, Zhao Wang, Zhongjun Xia, Tongyu Lin
Journal: Blood (2014)
Serially Measured Uric Acid Levels Predict Disease Severity and Outcome in Pediatric Pulmonary Arterial Hypertension
Authors: Lynn J. Leberkühne, Mark-Jan Ploegstra, Johannes M. Douwes, Beatrijs Bartelds, Marcus T. R. Roofthooft, Hans L. Hillege, Rolf M. F. Berger
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Cardiovascular disease (CVD) risk factors and health behaviors following cisplatin-based chemotherapy (CHEM): A multi-institutional study of testicular cancer survivors (TCS).
Authors: Mohammad Issam Abu Zaid, Chunkit Fung, AnnaLynn Williams, Howard D. Sesso, Sarah L Kerns, Darren R. Feldman, Robert James Hamilton, David J. Vaughn, Clair Beard, Hai Liu, Sophie D. Fossa, Lawrence H. Einhorn, Lois B. Travis
Journal: Journal of Clinical Oncology (2016)

129 Background: TCS are at increased risk of CVD, but few clinical studies have comprehensively evaluated CVD risk factors through physical exams, lipid panels, and health behaviors in North American patients. Methods: Eligible TCS were &lt; 50 y at diagnosis and treated with only first line CHEM. TCS underwent physical exams, had fasting lipid panels, and completed questionnaires regarding co-morbidities and health behaviors. Age, race, and educational status-matched controls (1:1) were chosen from the general population using the 2011-2012 National Health and Nutrition Examination Survey. Odds ratios (OR) of outcomes among TCS versus matched controls were estimated using logistic regression models. Results: We evaluated 680 consecutively enrolled TCS. Median age at diagnosis was 31 y (range, 15-49) and at clinical evaluation 38 y (range, 19-68). Median time since CHEM was 4.3 y (range, 1-30). Compared to normative controls, TCS were more likely to be overweight (OR = 1.65; 95% CI 1.26-2.16), have total cholesterol ≥ 240 mg/dL (OR = 2.19; 95% CI 1.12-4.28) and LDL ≥ 160 mg/dL (OR = 3.05; 95% CI 1.03-9.00), and report alcohol use &gt; 2 days/week (OR = 2.13; 95% CI 1.64-2.77). In contrast, they were more likely to have a waist circumference &lt; 40 inches (OR = 1.32; 95% CI 1.04-1.66); engage in vigorous (OR = 2.64; 95% CI 2.11-3.29) or moderate (OR = 1.62; 95% CI 1.30-2.03) physical activity, and not smoke (OR = 2.95; 95% CI 2.14-4.08). TCS were about 3 times more likely overall to report excellent, very good, or good health compared to controls (P &lt; 0.05). No significant differences were found comparing HDL, triglycerides, or self-reported hypertension (P &gt; 0.05). Conclusions: Although North American TCS appear more likely to exercise and abstain from smoking compared to normative controls, a greater proportion are overweight and have higher fasting total cholesterol and LDL levels. Health care providers should screen TCS for CVD risk factors, and encourage practices consistent with a healthy lifestyle. Future research should elucidate mechanisms of increased CVD risk and ultimately develop customized prevention and intervention strategies.
Contribution of immune system and tumor-related interferon signaling to epirubicin response in triple-negative (TN) breast cancers.
Authors: Giampaolo Bianchini, Maurizio Callari, Takayuki Iwamoto, Michela Riba, Lucia Vigano', Alberta Locatelli, Milvia Zambetti, Thomas Karn, Lajos Pusztai, Luca Gianni
Journal: Journal of Clinical Oncology (2015)

1081 Background: In HER2+ patients treated with HER2-targeted monoclonal antibodies in the NeoSphere trial, multivariate analysis showed a complex interplay between immune system and response (Gianni L SABCS 2012). High STAT1 and IGG metagens were associated with pCR, whereas high MHC1 and Interferon-inducible (IF.I) metagenes were associated with resistance. We sought to assess in TN tumors if there is a similar relationship between immune system and response to anthracyclines, which leads to immunogenic cell death Methods: We selected Affymetrix GEPs for 87 TN breast cancers (BCs) treated with neoadjuvant epirubicin monotherapy in the TOP trial (Desmedt C JCO 2011). Association between four previously define immune metagenes (IGG, STAT1, IF.I and MHC1), pCR and distant metastasis free survival (DMFS) were assessed. We assessed in 51 BC cell lines (25 TN) if isolated cells themselves also express those immune-related genes. Results: In TOP trial, immune metagenes were not associated with pCR in univariate analysis. In multivariate analysis, high STAT1 (OR 5.17 (1.66-16.1); p = 0.004) and low MHC1 (OR 0.19 (0.07-0.51); p = 0.001) were associated with pCR. Significance was retained when clinical variables and TOP2A amplification/deletion were included. In univariate analysis for DMFS, only high STAT1 was associated with lower risk of relapse (HR 0.62 (0.43-0.90); p = 0.012). In multivariate, high STAT1 (HR 0.26 (0.12-0.59); p = 0.001) and low IF.I (HR 2.75 (1.26-6.00); p = 0.01) were associated with lower risk of recurrence. Results were similar when only patients with residual disease were considered in the analysis. In BC cell lines, expression of MHC1-related genes was very heterogeneous from low to very high. A group of cell lines, TN and HER2+ in particular, expressed also some IF.I/STAT1 related genes. Conclusions: Multivariate analysis is needed to uncover the contribution of immune components to the response and prognosis of TN tumors treated with anthracyclines, which was similar to the involvement with response of HER2+ tumors to monoclonals. Interferon signaling, defined by STAT1 and IF.I metagenes, and MHC1 expression are related to both the immune system status and tumor cells.
원저 : 한국인에서 전격성 간부전의 임상적 특징 및 예후 인자
Authors: 신성재 ( Sung Jae Shin ), 안상훈 ( Sang Hoon Ahn ), 김희만 ( Hee Man Kim ), 김자경 ( Ja Kyung Kim ), 김병창 ( Byung Chang Kim ), 이재현 ( Jae Hyun Lee ), 백용한 ( Yong Han Paik ), 이관식 ( Kwan Sik Lee ), 한광협 ( Kwang Hyub Han ), 전재윤 ( Chae Yoon Chon ), 문영명 ( Young Myou)
Journal: Clinical and Molecular Hepatology (2004)

목적: 전격성 간부전은 선행하는 간질환이 없는 환자에서 바이러스나 약물 등에 의한 급성 간손상으로 인하여 간성뇌증 등의 합병증을 일으키는 치명적인 질환으로 적극적인 내과적 치료에도 불구하고 회복되지 않을 경우 응급 간이식만이 유일한 치료법으로, 발병 초기에 예후 인자 분석을 통한 적절한 시기의 이식 대상 환자군 선별이 중요하다. 이에 본 저자 등은 우리 나라에서의 전격성 간부전의 임상적 특징에 대하여 알아보고, 환자에 따라 임상적 진행 경과에서 예측할
Clinical risk or molecular risk: What matters in low grade gliomas? A study from the Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)
Authors: E. Franceschi, D. De Biase, A. Paccapelo, M. Reni, A. Mura, G. Tallini, C. Bortolotti, L. Volpin, G. Marucci, L. Cirillo, A. Pession, C. Ghimenton, R. Poggi, S. Bartolini, L. Albini Riccioli, A. Tosoni, C. Degli Esposti, D. Danieli, G. Genestreti, A.A. Brandes
Journal: Annals of Oncology (2016)
Implantable intravenous devices (“ports”) as a survivorship issue.
Authors: Aman Opneja, Amit Rout, Joseph Abraham, Gurkirat Gill, Kenneth David Miller
Journal: Journal of Clinical Oncology (2016)

9 Background: Women with early stage breast cancer often receive chemotherapy through implantable intravenous access devices (ports). There is little information on the duration of port use for breast cancer patients who have completed treatment. Methods: The EMR was searched for women who received adjuvant chemotherapy using a port for Stage I-III breast cancer between 2007- 2012. Data abstracted from the EMR included demographics, duration and type of chemotherapy, duration of port use and complications. Results: During the years 2007-2012, a total of 167 patients qualified for the study. 28 (16.8%) patients were excluded as complete data was not available. The Mean age of the remaining 127 women was 60 (SD: 1) years. The distribution of cancer stage was 18.1%, 59.1%, 22.8% of stage I, II, and III respectively. The median total length of duration of indwelling port was 506 days and median duration from chemotherapy completion to port removal was 299 days. The duration of time after completing treatment that the port remained in place was 0-6 months (31.5%), 6-12 months (25.2%), 12-24 months (24.4%), and &gt; 24 months (18.9%). Patients with stage III cancer had significantly longer time to port removal relative to patients with stage I and stage II cancer (p &lt; 0.005). Complications of ports (n = 4), all occurred during active treatment and included non-functioning/mispositioning (n = 2), and thrombosis (n = 2). Assuming the cost of port maintenance was $225 per visit and port maintenance was required every four weeks, the estimated average cost of maintaining the port after the completion of chemotherapy was $3,494 for this group of patients. Conclusions: Oncologists typically do not use the word “cure”; maintaining a port in place after chemotherapy may reinforce concerns about the risk of recurrence. This is highlighted by the fact that treatment type and hormone receptor status were not significantly associated with time of port removal. We found that 43% of patients still have their port in place one year after completing treatment and almost 19% of patients have their port in place greater than two years after completing treatment. The high cost and the possible psychological impact of leaving a port in place for long periods of time needs further study.
362PD Development and validation of a nomogram to predict the probability of recurrence in patients with major salivary gland cancers
Authors: C.-Y. Hung, C.-H. Lu, C.-T. Liu, P.-H. Chang, K.-Y. Yeh, S.-H. Li, Y.-C. Lin, T.-S. Yeh, Y.-S. Hung, W.-C. Chou
Journal: Annals of Oncology (2016)
MPTH-31. THE VARIATION OF THE SITES OF FUSION GENES IN SOLITARY FIBROUS TUMORS OCCURRED IN CENTRAL NERVOUS SYSTEM REGION
Authors: Mario Suzuki, Akihide Kondo, Satoshi Adachi, Hajime Arai
Journal: Neuro-Oncology (2016)

The 2016 World Health Organization classification of tumors of the central Nervous system reconstructed solitary fibrous tumor(SFT) and hemagiopericytoma(HPC) as one entity and adapting a grading system to accommodate this classification. The main reason of this reconstruction is the fact that SFT and HPS share inversions at 12q13, fusing the NAB2 and Stat6 genes. Recent studies also showed that there are variations in the fusion sites of these two genes in this tumor. We reviewed our cases of this tumor and tried to clear the relationships between tumor sites, fusion sites, pathological grading, and, the prognosis of patients. We studied the fusion sites of these genes with a direct sequence method and reviewed prognosis of patients and tumor sites from our hospital record. Two independent pathologists diagnosed the grade of tumors. Twelve tumors were available for this study including the tumors in orbit. Interestingly, there is a trend that the fusion sites of tumors in orbit may relate the prognosis of patients. However, there is no statistical difference in our study because of the small number of cases.
Determination of recommended phase II dose of ABTL0812, a novel regulator of Akt/mTOR axis, by pharmacokinetic-pharmacodynamic modelling
Authors: J. Alfon, L. Vidal, L. Gaba, I. Victoria, M. Gil, B. Laquente, M. Brunet, H. Colom, J. Ramis, H. Perez-Montoyo, M. Cortal, M. Gomez-Ferreria, P. Muñoz, T. Erazo, J.M. Lizcano, C. Domenech, P. Gascon
Journal: Annals of Oncology (2016)
Increased Oxidative Stress and Genomic Instability in Peripheral Blood and Bone Marrow of Individuals with Fanconi Anemia,
Authors: Kasiani C. Myers, Gretchen A Radloff, Melissa Scholz, Lisa Campbell, Jennifer E Hauser, Parinda A Mehta, Robin Mueller, Lisa Vormohr, Richard E. Harris, Qishen Pang, Stella M. Davies
Journal: Blood (2011)