tbuckley/cabot-search huggingface dataset:
Abstract 3540: Novel targeted combinational therapies for melanoma
Authors: Robert Suriano, Neha Y. Tuli, Jan Geliebter, Raj K. Tiwari, Marc Wallack
Journal: Cancer Research (2015)

Abstract The BRAFV600E mutation is frequently observed in over 60% of melanomas. Development of the small molecule inhibitor PLX4032, which specifically targets the mutated BRAF protein, offers a novel therapeutic approach by effectively blocking the activation of key signaling molecules of the mitogen-activated protein kinase (MAPK) pathway, such as Mek and Erk, effectively leading to arrest in cell proliferation. Provided that MAPK signaling targets the micropthalmia transcription factor (MITF), which is linked to the expression of various melanoma associated antigens (MAAs), we hypothesized that the inhibition of BRAFV600E can modulate the expression of MAAs. Since MAAs are essential in the development of a melanoma vaccine, due to their increased immunogenicity, altering their expression can be a useful immunotherapeutic approach to targeting melanoma. Using patient derived melanoma cell lines, which express various MAAs; our laboratory has developed a vaccinia virus based immunotherapeutic vaccine. These melanoma cell lines have been characterized by their status of BRAFV600E mutation and found to be either homozygous or heterozygous for the mutation. Inhibition of two key MAPK pathway molecules, namely Mek and Erk, denotes that the melanoma cell lines are responsive to PLX4032. Phenotypically, the cells’ invasive and migratory properties were also modulated upon treatment with PLX4032. Moreover, we observed that the expression of various MAAs was enhanced upon treatment with PLX4032. An amplification of gp100, MART-1 and tyrosinase expression on the RNA level as well as on the protein level was observed. Lastly, expression of MMAs was conserved in vivo following the analysis of melanoma cell xenografts in BALB/c nude mice. Based on our observations in that PLX4032 modulates MMA expression, further studies are warranted to determine the clinical effectiveness of combinational immunologic therapy using BRAFV600E inhibitors with our vaccinia virus melanoma cell line derived preparation. Citation Format: Robert Suriano, Neha Y. Tuli, Jan Geliebter, Raj K. Tiwari, Marc Wallack. Novel targeted combinational therapies for melanoma. [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 3540. doi:10.1158/1538-7445.AM2015-3540
Prediction of GBM outcome using combined analysis of MGMT protein expression and promoter methylation.
Authors: A. Lai, S. Lalezari, A. P. Chou, A. Tran, O. E. Solis, J. A. Carrillo, W. Chen, P. S. Mischel, R. M. Green, P. L. Nghiemphu, L. M. Liau, H. Wang, R. M. Elashoff, T. F. Cloughesy, W. H. Yong
Journal: Journal of Clinical Oncology (2011)

2003 Background: The standard of care for patients with newly-diagnosed glioblastoma (GBM) consists of postoperative radiotherapy and temozolomide (TMZ). O6-methylguanine-DNA methyltransferase (MGMT) provides resistance to TMZ, and MGMT promoter methylation correlates with improved treatment outcome presumably through silencing of MGMT protein expression. However, the prognostic significance of MGMT protein expression as assessed by immunohistochemistry (IHC) and its relationship with methylation remain unclear. Methods: We identified 418 newly-diagnosed GBM patients treated at UCLA/Kaiser with available pre-treatment FFPE tissue. We analyzed MGMT expression by IHC and MGMT promoter methylation by both methylation specific PCR (MSP) and bisulfite sequencing (BiSEQ) of 24 contiguous CpG sites containing the MSP region. Classification and regression tree analysis was performed on IHC and BiSEQ data to determine thresholds most predictive of outcome. Survival analyses were performed to assess the predictive value of these MGMT biomarkers separately and in combination. Results: MGMT expression alone was predictive of progression-free survival (PFS) and overall survival (OS) for GBM patients treated with TMZ. Patients with <30% staining on IHC had PFS*=11.3 mo and OS*=21.7 mo compared with PFS=7.3 mo and OS=16.7 mo for patients with ≥30% staining (*p<0.0001). We confirmed that MSP was predictive of outcome in our cohort but found that BiSEQ was superior to MSP for assessment of MGMT promoter methylation. Patients with ≥9 methylated CpG sites showed PFS*=13.3 mo and OS*=29.3 mo compared with PFS=8.1 mo and OS=16.1 mo for patients with <9 methylated CpG sites (*p<0.0001). Lastly, we observed that combined assessment of MGMT IHC and methylation provided improved predictive value (patients with low IHC and methylation had PFS=14.3 mo and OS=32.2 mo). Conclusions: MGMT IHC is a predictive biomarker for GBM patients treated with TMZ, and BiSEQ appears superior to MSP for methylation determination. Combined assessment of protein expression and methylation has better predictive value than either biomarker alone, and outcome for patients with low MGMT expression is dependent on MGMT methylation status.
Continued Response off Treatment After BRAF Inhibition in Refractory Hairy Cell Leukemia
Authors: Sascha Dietrich, Jennifer Hüllein, Michael Hundemer, Nicola Lehners, Alexander Jethwa, David Capper, Till Acker, Boyan Garvalov, Mindaugas Andrulis, Carolin Blume, Julia Meissner, Stefan Fröhling, Christof von Kalle, Hanno Glimm, Anthony D. Ho, Thorsten Zenz
Journal: Blood (2012)
Abdominal vs Minimally Invasive Hysterectomy—Reply
Authors: Jason D. Wright, Dawn L. Hershman
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 3959: microRNA as a potential biomarker for hepatitis C virus mediated end-stage liver disease progression
Authors: Ratna B. Ray
Journal: Cancer Research (2015)

Abstract HCV accounts for the most frequent cause of end stage liver disease–including hepatocellular carcinoma (HCC), and liver transplantation in the western world. Since HCV-mediated end stage liver diseases are diagnosed much later after infection, identifying the HCV infected individuals at high risk for developing HCC will permit surveillance, early detection and chemoprevention. Liver biopsy or Fibroscan (often used now) has major limitations. Moreover, neither liver biopsy nor fibroscan can predict who will progress to more severe disease. The relationship between HCV infection and microRNA (miRNA) expression is of considerable interest in understanding liver disease progression to HCC. In this present study, we performed a systematic screening approach to identify upregulated miRNAs in the plasma/serum of HCV infected patients with different stages of hepatic histological disease severity. We initially screened serum samples of HCV infected patients with fibrosis and compared with sera of healthy volunteers using serum miRNA array profiling, and identified a group of modulated miRNAs. Subsequent study demonstrated that miR-20a in HCV infected fibrosis and HCC patients sera were significantly upregulated when compared with that of healthy volunteers or non-HCV associated liver disease. However, there was no correlation between the serum levels of miR-20a with HCV viral loads. We next investigated longitudinal plasma samples from HCV-infected patients. Our results suggested that miR-20a remained unaltered in HCV-infected patients who progressed from acute to chronic infection. These data provide evidence that plasma/serum level of miR-20a has potential as sensitive and cost-effective biomarkers for early detection of HCV mediated liver disease. Conclusion: The circulating miR-20a may serve as a potential for predictive biomarker in HCV mediated end stage liver disease. Citation Format: Ratna B. Ray. microRNA as a potential biomarker for hepatitis C virus mediated end-stage liver disease progression. [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 3959. doi:10.1158/1538-7445.AM2015-3959
P0595 : High frequency of active HCV infection among seropositives in West Africa and evidence for multiple transmission pathways
Authors: J. Layden, N. Mora, R.O. Phillips, S. Owusi-Ofori, F.S. Sarfo, S. Kliethermes, D. Owusu, K. Nelson, L. Dugas, A. Luke, D. Shoham, J.C. Forbi, Y.E. Khudyakov, R.S. Cooper
Journal: Journal of Hepatology (2015)
SEDACIÓN PROFUNDA CON PROPOFOL CONTROLADA POR ENDOSCOPISTA EN LA CPRE. SEGURIDAD Y FACTORES ASOCIADOS A COMPLICACIONES
Authors: R Uribarrena Amezaga, L Luzón Solanas, L Ollero Domenche, J Val Perez, EM Sierra Moros, MT Soria Santeodoro
Journal: Endoscopy (2015)

Introducción: La sedación con propofol por no anestesistas está muy extendida en la endoscopia digestiva. La CPRE es una técnica endoscópica avanzada que tiene una mayor complejidad para la sedación.
Abstract 1070: Epigenetic silencing of galectin-12 in colorectal cancer
Authors: Eva-Maria Katzenmaier, Johannes Gebert, Matthias Kloor, Jürgen Kopitz
Journal: Cancer Research (2015)

Abstract Aim/Background: Galectins constitute a family of ß-galactoside binding proteins some of them known to be involved in colorectal tumorigenesis. Our previous work suggests that sodium butyrate can induce galectin-12 expression in CRC cell lines. How this might be exerted is largely unexplored. In the present study we examined the potential epigenetic regulation of galectin-12 expression in colorectal cancer cell lines and primary tumors. Material and Methods: For DNA-methylation analysis 4 microsatellite unstable (MSI) and 5 microsatellite stable (MSS) human CRC cell lines were treated with 5-Aza-2`deoxycytidine (5-Aza-dC) for 72h. Changes in galectin-12 expression were evaluated by RT-PCR analysis. Galectin-12 promoter methylation was determined by bisulfite treatment and genomic DNA sequencing of single clones in the CRC cell line SW707 as well as in FFPE specimens from 10 primary colorectal tumors (MSI: n = 5; MSS: n = 5). Results: Treatment with 5-Aza-dC led to de novo expression of galectin-12 transcript in 4/9 (44%) of colorectal cancer cell lines. We identified a CpG island in the galectin-12 promoter region that was found to be hypomethylated upon 5-Aza-dC treatment in SW707 cells and to be associated with concomitant de novo galectin-12 mRNA expression. When primary tissues were examined we observed galectin-12 promoter hypomethylation in healthy colon mucosa but significant hypermethylation of this promoter region in corresponding tumor tissue. Conclusions: This study for the first time shows that galectin-12 promoter methylation represses galectin-12 expression in colorectal tumor cells independent of their MSI status. In CRC cell lines this effect can be reversed by butyrate but in human colon primary tumors might be refractory to these effects of butyrate. Re-expression of galectin-12 may be a potential therapeutic strategy to constrain colorectal tumor growth. Citation Format: Eva-Maria Katzenmaier, Johannes Gebert, Matthias Kloor, Jürgen Kopitz. Epigenetic silencing of galectin-12 in colorectal cancer. [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 1070. doi:10.1158/1538-7445.AM2015-1070
FDG PET Scan Alone Better Predicts Progression Free Survival at 2 Years Compared to CT Imaging in Aggressive Histology Non-Hodgkin’s Lymphoma Following Initial Anthracycline-Based Chemotherapy.
Authors: Gregory A. Wiseman, Malik E. Juweid, Eric M. Rohren, James E. Wooldridge, Michael M. Graham
Journal: Blood (2004)
Abstract 4449: A novel Porcupine inhibitor is effective in the treatment of cancers with RNF43 mutations
Authors: Zhiyuan Ke, Babita Madan, Shermaine Q.y. Lim, Sifang Wang, Jenefer Alam, Soo Yei Ho, Duraiswamy Athisayamani Jeyaraj, Kakaly Ghosh, Yun Shan Chew, Li Jun Ding, Vithya Monoharan, Vishal Pendharkar, Esther Ong, Jeffrey Hill, Kanda Sangthongpitag, Thomas Keller, May Ann Lee, David M. Virshup
Journal: Cancer Research (2015)

Abstract Various mutations in the Wnt pathway contribute to aberrant activation of Wnt signaling, which is implicated in multiple cancers. Besides the mutation of Adenomatous polyposis coli (APC) or beta-catenin which causes the continuous activation of Wnt signaling by stabilizing beta-catenin, there are mutations of other genes such as RNF43 that regulate Wnt signaling at the level of the ligand or cell surface receptor. Inhibition of the secretion of all human Wnts by blocking their palmitoleoylation by the O-acyltransferase, Porcupine (PORCN), could be an alternative therapeutic approach. Here we have developed a compound with a novel pharmacophore that can inhibit PORCN activity and hence Wnt signaling in nanomolar concentration. In vivo efficacy study demonstrated that the compound is highly efficacious in preventing tumor growth in genetic modification model MMTV-WNT1 mouse. We have identified a subset of pancreatic cancer, cholangiocarcinoma and mucinous ovarian cancer cell lines that are sensitive to the compound. Most of these cell lines harbor mutations in RNF43. Xenograft tumor models derived from the cancer cell lines were found to be sensitive to the compound. Our results demonstrate that inhibiting the Wnt/beta-catenin pathway by targeting PORCN with small-molecule inhibitors in a subset of cancers with mutation in RNF43 is a feasible and nontoxic strategy to overcome the problem of redundancy of Wnts, thereby, providing new option for therapy in diseases with up regulated Wnt expression. Citation Format: Zhiyuan Ke, Babita Madan, Shermaine Q.y. Lim, Sifang Wang, Jenefer Alam, Soo Yei Ho, Duraiswamy Athisayamani Jeyaraj, Kakaly Ghosh, Yun Shan Chew, Li Jun Ding, Vithya Monoharan, Vishal Pendharkar, Esther Ong, Jeffrey Hill, Kanda Sangthongpitag, Thomas Keller, May Ann Lee, David M. Virshup. A novel Porcupine inhibitor is effective in the treatment of cancers with RNF43 mutations. [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 4449. doi:10.1158/1538-7445.AM2015-4449
FOLFIRINOX for locally advanced or metastatic pancreatic cancer: a single institution retrospective review
Authors: Mitsuhito Sasaki, Hideki Ueno, Reiko Makihara, Futa Koga, Satoshi Shiba, Yasunari Sakamoto, Shunsuke Kondo, Chigusa Morizane, Masafumi Ikeda, Takuji Okusaka
Journal: Annals of Oncology (2015)
PIM as a Rational Target for B-Cell Lymphomas.
Authors: Cristina Gomez-Abad, Helena Pisonero, Juan F Leal, Giovanna Roncador, Jose A. Martinez-Climent, Margarita Sánchez-Beato, Carmen Blanco-Aparicio, James Robert Bischoff, Miguel A. Piris
Journal: Blood (2009)
Genetics of HbF and HbF Response to Hydroxyurea In Pediatric Sickle Cell Disease: A Multi-Site Pilot Analysis of Candidate SNP Variants
Authors: Nancy S. Green, Katherine Ender, Farzana Pashankar, Catherine Driscoll, Patricia Giardina, Craig A. Mullen, Lorraine Clark, Jennifer Crotty, Mara Burney, Carolyn Hoppe, Sandra Barral
Journal: Blood (2010)
Non-Lineage/Stage Restricted Effects of a Gain-of-Function Mutation in Tyrosine Phosphatase Ptpn11 (Shp2) on Malignant Transformation of Hematopoietic Cells
Authors: Dan Xu, Xia Liu, Wen-Mei Yu, Howard J. Meyerson, Stanton L. Gerson, Cheng-Kui Qu
Journal: Blood (2011)
Abstract 5339: Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo
Authors: Yuanhui Zhang, Yuan Wang, Lina Wang, George Aslanidi, Arun Srivastava, Changquan Ling, Chen Ling
Journal: Cancer Research (2015)

Abstract Traditional Chinese medicine (TCM) has held, and still holds, an important position in primary health care in China, especially in the rural areas. However, scientific evidence of its mechanism is, for the most part, limited and additional better-designed laboratory research is needed. To date, numerous leading chemical compounds from TCM drugs have been identified and evaluated for their anti-tumor effects. However, little effort has been made on the protein-encoding genes isolated from TCM drugs, and the delivery of these genes into malignant cells through recombinant adeno-associated viral (rAAV) vectors has not been attempted. For example, Trichosanthin (TCS), an antiviral plant defense protein found in the root tuber of a TCM herb, Trichosanthes kirilowii, has been used in anti-HIV clinical trials in the USA. Its enzymatic activities were recognized as type I ribosome-inactivating protein. Although the nucleotide sequence of the TCS gene was determined more than 20 years ago, to date, there was little report to deliver TCS-encoding gene into malignant cells. In the present studies, we synthesized the cDNAs of five known cytotoxic proteins isolated from TCM drugs and the FLAG epitope-tagged cDNAs were subcloned into a rAAV plasmid vector. The expression of mRNA was confirmed by RT-PCR and protein expression by Western blot assays against the FLAG tag, respectively. Among these genes, TCS gene yielded the most promising results for the inhibition of cancer cell growth in vitro. The over-expressed TCS functioned as a type I ribosome inactivating protein, followed by inducing apoptosis that is associated with the Bcl-PARP signaling pathway. Next, rAAV vectors containing the TCS gene driven by a liver cancer specific promoter, α-fetoprotein promoter (AFPp) were generated and tested. The results indicated that rAAV-AFPp-TCS vectors significantly inhibited the growth of hHCC cell lines in vitro as well as hHCC tumor growth in vivo following intra-tumor injections in a murine xenograft model. These studies suggest that the use of TCM cytotoxic genes may prove to be a useful therapeutic strategy for treating human cancers in general, and liver tumors in particular. Note: This abstract was not presented at the meeting. Citation Format: Yuanhui Zhang, Yuan Wang, Lina Wang, George Aslanidi, Arun Srivastava, Changquan Ling, Chen Ling. Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo. [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 5339. doi:10.1158/1538-7445.AM2015-5339
Five Years Update Results of Basiliximab (BAMAB) Therapy for Acute Refractory Graft Versus Host Disease (AGVHD).
Authors: Vaneuza A.M. Funke, Carmem M. Bonfim, Marco A. Bitencourt, Daniela C. Setubal, Jefferson Ruiz, Carlos R. Medeiros, Jose Z. Neto, Ricardo Pasquini
Journal: Blood (2004)
Length of Storage of Red Blood Cells and Patient Survival After Blood Transfusion
Authors: Märit Halmin, Klaus Rostgaard, Brian K. Lee, Agneta Wikman, Rut Norda, Kaspar René Nielsen, Ole B. Pedersen, Jacob Holmqvist, Henrik Hjalgrim, Gustaf Edgren
Journal: Annals of Internal Medicine (2016)

Background: Possible negative effects, including increased mortality, among persons who receive stored red blood cells (RBCs) have recently garnered considerable attention. Despite many studies, including 4 randomized trials, no consensus exists. Objective: To study the association between the length of RBC storage and mortality in a large population-based cohort of patients who received transfusions, allowing detection of small yet clinically significant effects. Design: Binational cohort study. Setting: All transfusion recipients in Sweden and Denmark. Patients: 854 862 adult patients who received transfusions from 2003 to 2012. Measurements: Patients were followed from first blood transfusion. Relative and absolute risks for death in 30 days or 1 year in relation to length of RBC storage were assessed by using 3 independent analytic approaches. All analyses were conducted by using Cox proportional hazards regression. Results: Regardless of the analytic approach, no association was found between the length of RBC storage and mortality. The difference in 30-day cumulative mortality between patients receiving blood stored for 30 to 42 days and those receiving blood stored for 10 to 19 days was −0.2% (95% CI, −0.5% to 0.1%). Even among patients who received more than 6 units of RBCs stored for 30 days or longer, the hazard ratio of death was 1.00 (CI, 0.96 to 1.05) compared with those who received no such units. Limitation: Observational study; risk of confounding by indication. Conclusion: Consistent with previous randomized trials, this study found no association between the length of storage of transfused RBCs and patient mortality. Results were homogeneous, with differences in absolute mortality consistently less than 1% among the most extreme exposure categories. These findings suggest that the current practice of storing RBCs for up to 42 days does not need to be changed. Primary Funding Source: The Swedish Research Council, Swedish Heart–Lung Foundation, Swedish Society for Medical Research, Strategic Research Program in Epidemiology at Karolinska Institutet, and Danish Council for Independent Research.
Intensive Care Management and Outcomes In Allogeneic Hematopoietic Stem Cell Transplantation Recipients
Authors: Etienne Lengliné, anne-Sophie Moreau, Sylvie Chevret, Frederic Pene, François Blot, Jean-Henri Bourhis, Agnes Buzyn, Benoît Schlemmer, Gérard Socié, Elie Azoulay
Journal: Blood (2013)
The Role of Livin, An Inhibitor of Apoptosis Protein, in Thrombopoiesis.
Authors: Ihab Abd-Elrahman, Varda Deutsch, Klilah Hershko, Tsahi Noyman, Itay Lazar, Boaz Nachmias, Riki Perlman, Dina Ben-Yehuda
Journal: Blood (2008)