tbuckley/cabot-search huggingface dataset:
Abstract 833: Benzyl isothiocyanate mediates glucose uptake through AKT activation in breast cancer cells
Authors: Ruchi Roy, Shivendra V. Singh
Journal: Cancer Research (2016)

Abstract We have shown previously that benzyl isothiocyanate (BITC) administration retards the development of mouse mammary tumors driven by Her-2 oncogene proving in vivo evidence for its chemopreventive efficacy. However, we also observed an increase in glucose uptake by tumor in BITC treatment group compared with control mice. Proteomics using tumors from control and BITC-treated mice revealed changes in proteins related to metabolism. Thus, we studied the mechanism by which BITC increases glucose uptake using four cell lines with different genetic backgrounds (e.g., ER+, ER-, HER-2+, triple negative). Consistent with in vivo findings, BITC treatment enhanced the protein levels of glucose transporters (GLUT1 and GLUT4) regardless of ER, HER-2 or p53 status. On the other hand, lactate dehydrogenase (LDH) was downregulated in response to BITC treatment. Pyruvate kinase (PKM2) as well as tricarboxylic cycle (TCA cycle) related enzymes (IDH1, PDH, MDH) were upregulated in BITC treated cells compared with control. In agreement with these results, BITC treatment increased glucose, pyruvate, and acetyl-CoA levels but decreases lactate level. These results suggested that elevated glucose after BITC treatment was largely utilized through TCA cycle. Because AKT is known to regulate tumor metabolism including glycolysis and oxidative phosphorylation, we explored its involvement in BITC-mediated metabolic alterations. To our surprise, BITC treatment resulted in a marked increase in activation of AKT. Pharmacological inhibition of AKT antagonized BITC-mediated increase in GLUT1 expression as well as increase in glucose and pyruvate levels. In addition, AKT inhibition augmented BITC-mediated inhibition of cell survival (colony formation), induction of apoptosis, and suppression of migration in human breast cancer cells. Based on these findings, we propose that mammary cancer chemopreventive efficacy of BITC may be augmented by a combination regimen involving an AKT inhibitor. This study was supported by the grantCA129347 awarded by the National Cancer Institute. Citation Format: Ruchi Roy, Shivendra V. Singh. Benzyl isothiocyanate mediates glucose uptake through AKT activation in breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 833.
Characterization and Comparison of Cord Blood (CB) vs Adult Peripheral Blood (APB) CD4+CD25+ NAÏVE and Antigen Presentation Cell (APC) Induced T Regulatory (TREG): Significant Increase in APC Induced CB vs APB CD4+/CD25+/CTLA-4+ TREG.
Authors: Chih-Chao Chang, Carmella van de Ven, Prakash Satwani, Nora Oberfeld, Lynn Simpson, Mitchell S. Cairo
Journal: Blood (2004)
Anemia and the Use of Erythropoietic-Stimulating Agents with Ruxolitinib in the COMFORT-II Study
Authors: Mary Frances McMullin, Claire N. Harrison, Dietger Niederwieser, Hilde Demuynck, Nadja Jäckel, Andres Sirulnik, Alison Wearver, Viktoriya Stalbovskaya, Jean-Jacques Kiladjian, Haifa Kathrin Al-Ali
Journal: Blood (2011)
Abstract 2201: Tea nanoparticle, a safe and biocompatible nanocarrier, greatly potentiates the anticancer activity of doxorubicin
Authors: Yi-Jun Wang, Yujian Huang, Nagaraju Anreddy, Guan-Nan Zhang, Yun-Kai Zhang, Meina Xie, Derrick Lin, Dong-Hua Yang, Mingjun Zhang, Zhe-Sheng Chen
Journal: Cancer Research (2016)

Abstract An infusion-dialysis based procedure has been developed as an approach to isolate organic nanoparticles from green tea. Tea nanoparticle (TNP) can effectively load doxorubicin (DOX) via electrostatic and hydrophobic interactions. We established an ABCB1 overexpressing tumor xenograft mouse model to investigate whether TNP can effectively deliver DOX into tumors and bypass the efflux function of the ABCB1 transporter, thereby increasing the intratumoral accumulation of DOX and potentiating the anticancer activity of DOX. MTT assays suggested that DOX-TNP showed higher cytotoxicity toward CCD-18Co, SW620 and SW620/Ad300 cells, as compared to DOX. Animal study revealed that DOX-TNP resulted in a greater inhibitory effect on the growth of SW620 and SW620/Ad300 tumors than DOX alone. The cTnI levels in mice showed that TNP had no cardiotoxicity and DOX-TNP had moderate cardiotoxicity. Blood Smear tests demonstrated that TNP and DOX-TNP did not cause neutropenia or thrombocytopenia in mice. Therefore, TNP is a safe nanocarrier with excellent biocompatibility and minimal toxicity. In pharmacokinetics study, DOX-TNP greatly increased the SW620 and SW620/Ad300 intratumoral concentrations of DOX, as compared to DOX alone. But DOX-TNP had no effect on the plasma concentrations of DOX up to 240 min after administration. Furthermore, ex vivo IHC analysis of SW620 and SW620/Ad300 tumor sections revealed evidence of prominent antitumor activity of DOX-TNP. In conclusion, our findings suggested that natural nanomaterials could be useful in combating multidrug resistance (MDR) in cancer cells and potentiating the anticancer activity of chemotherapeutic agents in cancer treatment. Citation Format: Yi-Jun Wang, Yujian Huang, Nagaraju Anreddy, Guan-Nan Zhang, Yun-Kai Zhang, Meina Xie, Derrick Lin, Dong-Hua Yang, Mingjun Zhang, Zhe-Sheng Chen. Tea nanoparticle, a safe and biocompatible nanocarrier, greatly potentiates the anticancer activity of doxorubicin. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2201.
An interdisciplinary process for improving pain management in oncology.
Authors: Harold W. Goforth, Diana Karius, Kathy Day, Anne Fitz, Patti Akins, Julie Fetto, Amy E. Guthrie, James Stevenson
Journal: Journal of Clinical Oncology (2013)

182 Background: Upcoming changes in Medicare reimbursement models take into account HCAHP scores, and over the next 1-3 years, penalties will be enacted towards those institutions falling below a standard on their publicly available HCAHP scores. The HCAHP pain domain can be one of the most challenging to impact directly due to lack of pain management knowledge, proper assessment skills, expertise in managing complex pain syndromes, and the heterogeneity of pain symptomatology reported by advanced cancer patients. Methods: This project identified inpatient oncology units with suboptimal HCAHP scores. The objective was to improve HCAHP pain scores to &gt; 90 th percentile. Nursing intervention focused on five primary areas: a) A requirement to attend a mandatory class on malignant pain management; b) making available nursing pain mentors; c) a requirement to address pain during rounds with physicians; d) priority access to medications to address pain; and, e) encouraging event reporting for uncontrolled pain issues. Resident physicians were provided expectations for pain management and attended a mandatory class on malignant pain taught by a palliative medicine attending physician. A palliative medicine physician was also assigned to the unit to evaluate patients with pain scores &gt; 6/10 or complex pain needs. An algorithm for pain control was designed to include a timeline for intervention as well as an escalation process for slow or inadequate physician response. A hand-off report was provided to the charge nurse by the senior resident physician at the end of each day that included a tentative plan for treating any escalating pain. Results: All initiatives were implemented in September 2012. By February 2013, Pain HCAHP scores increased 10% over the entire Taussig Cancer Institute, and increased 20% for the solid tumor oncology unit. This placed all units who received this targeted intervention above the 90 th percentile as compared to other hospitals on the HCAHPS pain score. Conclusions: A well-defined collaborative model between physicians and nursing produced measurable improvement in pain outcomes for oncology inpatients. An interdisciplinary approach is essential for the management of complex pain issues in an oncology patient population.
Acute Neurologic Reaction to Promethazine
Authors: Kenneth F. Swaiman
Journal: New England Journal of Medicine (1960)

A BRIEF glance at the medical literature over the past few years gives sufficient assurance of the relatively frequent and unusual clinical pattern of phenothiazine toxicity.1 2 3 4 This report is not intended as a review of the literature on this subject.As would most likely be expected, even drugs of this group considered least toxic will from time to time cause difficulty of a severe degree. The following report demonstrates such an episode initiated by a small single dose of promethazine.Case ReportA 5-year-old boy became ill 9 days before admission, with symptoms of fever, cough and coryza. The temperature . . .
Can neutrophil-to-lymphocyte ratio be used to identify patients with metastatic renal cell carcinoma who may gain greater benefit from cytoreductive nephrectomy?
Authors: Daphne Dai, Yada Kanjanapan, Edmond Michael Kwan, Desmond Yip, Nathan Lawrentschuk, Ian D. Davis, Arun Azad, Mark Rosenthal, Shams Ul Arifeen, Mahmood Alam, Peter Gibbs, Ben Tran
Journal: Journal of Clinical Oncology (2015)

490 Background: Two randomized trials demonstrated survival benefits associated with cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the interferon era. However, the role of CN in the era of targeted therapies is yet to be defined. In recent years, neutrophil-to-lymphocyte ratio (NLR) has emerged as a clinically useful prognostic marker in several cancers including mRCC. In this multi-center retrospective study, we aim to assess the impact of CN in mRCC and the value of NLR in risk stratification and patient selection. Methods: Patients with de novo mRCC diagnosed between 2006 and 2012 from three large Australian hospitals were identified using an electronic database. Data regarding clinicopathological features, MSKCC risk group, NLR at the time of metastatic diagnosis, treatments received and survival were collected. NLR ≥5 was used as the cutoff for statistical analyses. Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses used the Cox proportional hazards method. Results: Our study identified 91 de novo mRCC patients. CN was performed in 46 (51%) patients. Patients who underwent CN were more likely to be younger (median age 59.0 vs. 64.6, p=0.019), and to have received systemic therapy post CN (91% vs. 76%, p=0.043). Median overall survival (mOS) was significantly improved in patients who underwent CN (23.0 mo vs. 10.9 mo, p=0.039). Patients with NLR &lt;5 also had superior mOS (16.7 mo vs. 6.2 mo; HR 0.53; 95% CI; 0.24-0.84; p=0.013). While CN was associated with substantially improved survival in patients with both NLR &lt;5 (mOS 31.1 mo vs. 7.0 mo; HR 0.41; 95% CI, 0.18-0.64; p=0.0009) and NLR ≥5 (mOS 10.9 mo vs. 2.3 mo; HR 0.33; 95% CI, 0.11-0.69; p=0.009), the absolute survival difference was greater in patients with baseline NLR &lt;5. Significant survival benefits associated with CN were maintained in multivariate analyses (HR 0.31; 95% CI, 0.18-0.55; p&lt;0.0001). Conclusions: CN is associated with significantly improved OS in de novo mRCC. The incremental survival benefit associated with CN was seen irrespective of NLR.
Abstract LB-103: Molecular exploitation of oncogenic stress in melanoma management
Authors: Raj Kumar, Zhenyu Ji, Benchun Miao, Ching-Ni Jenny Njauw, Hensin Tsao
Journal: Cancer Research (2016)

Abstract Oncogenic B-RAF and N-RAS mutations are frequently reported in mitogen-activated protein kinase pathways of tumors. BRAF and NRAS mutations are found in more than 30% of all human tumors and 43% (88% V600E, 10% V600K) and 30% (48% Q61K, 40% Q61R) of malignant melanoma. These mutations were considered mutually exclusive except a few (0.7%) cases. BRAF and NRAS mutations are an important clinical marker and prognostic factor in metastatic melanoma. Recently developed BRAFV600E targeted therapies demonstrate significant clinical benefit but the targeted therapeutic options for NRAS-mutant melanomas are still under intense investigation. Importantly, BRAF and NRAS mutations are mutually exclusive, meaning that tumors are rarely found with these two mutations and are reported as lethal to the cancer cells. Hence, molecular behavior and interaction between BRAF and NRAS mutant proteins underline phenotypic complexity which is poorly understood. In the current study, we aimed to determine the translational significance of BRAF and NRAS mutations and their products in cell based studies with metastatic melanoma cell lines. Our lab sought to investigate the common molecular therapeutic target(s) of these genes, responsible for synthetic lethality. By using remote inducible expression system of BRAFV600E mutant gene in NRASQ61R mutant cell lines and vice versa. It is found that 25% (2/8) NRASQ61R mutant cell lines are sensitive to BRAFV600E and NRASQ61R mutation co-expression and have slow-growth phenotype with cells displaying hallmarks of oncogene-induced senescence, apoptosis and cell cycle arrest, more over rescued with BAP1 ectopic expression. While some NRAS mutant cell lines showed no lethal effect to BRAFV600E mutation expression which is well explained by human phospho-kinase array. These preliminary results suggest a complex interplay of tumor drivers (BRAF and NRAS) and passengers (X-factors) in cancer biology that need to be investigated in detail in melanoma. Citation Format: Raj Kumar, Zhenyu Ji, Benchun Miao, Ching-Ni Jenny Njauw, Hensin Tsao. Molecular exploitation of oncogenic stress in melanoma management. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-103.
Abstract 2741: A novel branched DNA-based multiplex method for telomere analysis at the single-cell level by flow cytometry
Authors: Steve Lai, Leslie Sias, Castle Funatake
Journal: Cancer Research (2016)

Abstract Telomeres are protective structures at the ends of chromosomes, containing multiple repeats of the repetitive sequence (TTAGGG) in vertebrates. It undergoes progressive shortening during normal aging. Abnormalities in the regulation of telomere length are implicated in various diseases including cancers. Current methods for telomere analysis are tedious and lack the flexibility to allow identification of unique cell subsets in a heterogeneous sample. Here we describe a novel flow cytometric method for analyzing relative telomere length at the single-cell level based on the branched DNA technology. This method, named PrimeFlow Assay can be combined with antibody staining and mRNA detection enabling simultaneous analysis of telomere length as well as protein and RNA for a comprehensive view in any specific cell subset. With this method, we investigated various cell lines and primary cells of human and mouse origin. Our results indicate that transformed cell lines possess longer telomeres than primary cells. In human peripheral blood mononuclear cells, we observed that lymphocytes had longer telomeres compared to monocytes, consistent with previously published results by another flow cytometric method. These data demonstrate that the PrimeFlow assay is a valuable method for high-throughput analysis of relative telomere length that may be combined with the analysis of protein and gene targets and, thus, provides data at the single-cell level for a more complete understanding of sample heterogeneity. Citation Format: Steve Lai, Leslie Sias, Castle Funatake. A novel branched DNA-based multiplex method for telomere analysis at the single-cell level by flow cytometry. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2741.
Abstract 200: PDLIM2 phosphorylation in determining breast cancer phenotype
Authors: Orla T. Cox, Janina Berghoff, Deirdre A. Buckley, Rosemary O’Connor
Journal: Cancer Research (2016)

Abstract Several genes that are involved in cancer progression are induced by Insulin-like Growth Factor-1 (IGF-1). One of them encodes the PDZ-LIM protein PDLIM2, which is localized at the cytoskeleton and nucleus in epithelial and hematopoietic cells. PDLIM2 is repressed in certain cancers including breast cancers, but it is highly expressed in invasive cancer cells in triple negative breast cancer (TNBC), where it has also been associated with poor survival. PDLIM2 regulates the stability and activity of transcription factors including beta catenin, STATs, NFκB and IRFs and has been associated with ubiquitination and destabilization of proteins such as NF-κB, E-cadherin, and p27KIP1. However, PDLIM2 itself is also regulated by posttranslational modifications, but how this controls PDLIM2 activity is still largely unclear. Therefore, this study aimed to investigate PDLIM2 phosphorylation and its effect on PDLIM2 sub-cellular location and function in transcription factor regulation. The PDLIM2 protein sequence includes multiple potential phosphorylation sites and it migrates as several distinct phosphatase-sensitive species in SDS PAGE and 2D electrophoresis, indicating phosphorylation at several residues. Using cellular fractionation and immunofluorescence we show that PDLIM2 accumulates in the nucleus in response to cell stimulation with IGF-1 or TGFβ. Moreover, we show that inhibitors of Rho Kinases suppress PDLIM2 phosphorylation in response to these stimuli. In addition, we demonstrate that mutation of the predicted Rho Kinase phosphorylation sites in PDLIM2 reduce protein stability, an effect that can be reversed by application of proteasomal inhibitor. Overall, our results indicate that phosphorylation by Rho kinases plays an important role in the subcellular location and regulation of PDLIM2 function, which opens a new avenue in targeting PDLIM2 activity in invasive cancer cells. Citation Format: Orla T. Cox, Janina Berghoff, Deirdre A. Buckley, Rosemary O’Connor. PDLIM2 phosphorylation in determining breast cancer phenotype. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 200.
Abstract 489: NGS analysis of the single CTC or DTC isolated and subtyped by the integrated subtraction enrichment and immunostaining-FISH
Authors: Peter Lin
Journal: Cancer Research (2016)

Abstract Majority of the circulating or disseminated tumor cell (CTC or DTC) detection methodologies rely on existence of epithelial markers (such as EpCAM and/or cytokeratins) on tumor cells. However, highly heterogeneous expression or even absence of EpCAM, and down-regulation of both EpCAM and cytokeratins in CTCs/DTCs during epithelial-mesenchymal transition (EMT) has been reported elsewhere, resulting in significant false negative detection of those uncatchable and invisible CTCs/DTCs. A novel strategy integrating subtraction enrichment which efficiently enriches non-hematopoietic tumor cells shed from various types of solid tumor into biofluid including peripheral blood, bone marrow, ascites, pleural effusion, and cerebrospinal fluid (CSF), with immunostaining-FISH (iFISH), which enables in situ phenotypic immunofluorescent staining of tumor biomarker and chromosomal FISH on the identical tumor cell, has shown its unique advantage in terms of detecting CTCs/DTCs with higher sensitivity and specificity. Diversified CTCs/DTCs could be identified and subtyped upon specific chromosome ploidy and tumor biomarker expression, and each subtype of CTCs/DTCs respectively correlate with therapeutic drug sensitivity or resistance, tumor metastasis or relapse. Whole genome amplification and subsequent next generation sequencing (NGS) analysis performed on the single subtyped breast, pancreatic, gastric and NSCLC cancer CTC or DTC targeted by iFISH, and collected by means of a microscopic cell manipulator is able to reveal ploidy of all the chromosomes and status of either unknown genes or a series of known oncogenes including HER2, Kras, BRAF, etc. It is anticipated that SE-iFISH could guide and promote more significant single cell based genomic and functional analyses of CTCs and/or DTCs. Citation Format: Peter Lin. NGS analysis of the single CTC or DTC isolated and subtyped by the integrated subtraction enrichment and immunostaining-FISH. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 489.
Donor Lymphocyte Infusion for Relapsed Hematological Malignancies After Allogeneic Hematopoietic Cell Transplantation: Prognostic Relevance of the Initial CD3+ T Cell Dose
Authors: Merav Bar, Barry Storer, Benedetto Bruno, Parameswaran Hari, Thomas Chauncey, Yoshihiro Inamoto, Paul J. Martin, Rainer Storb, David G. Maloney, Brenda M. Sandmaier, Mary E.D. Flowers
Journal: Blood (2012)