tbuckley/cabot-search huggingface dataset:
Abstract 4377: Proper migration of mammalian prostate stem cells to the area of the prostate gland in zebrafish
Authors: Pudur Jagadeeswaran, Uvaraj P. Radhakrishnan, Seongcheol Kim, Surendra Kumar Rajpurohit, Daxing Xie, Jer-Tsong Hsieh
Journal: Cancer Research (2011)

Abstract Androgen independent prostate cancer contributes to the maximum mortality in prostate cancer patients. One school of thought is that these cancer cells arise in metastatic sites where the cancer cells take on stem cell behavior similar to the stem cell behavior observed in normal prostate gland. Thus, understanding prostate gland stem cells and their migration pattern may provide clues to their biology which may have applications in their migration during metastasis. To understand the migration of mammalian prostate stem cells we used zebrafish as a model. We have previously established zebrafish as a model to study prostate cancer because we found the presence of prostate-like- cells around the zebrafish testes. In this abstract we further characterized location of normal prostate-like cells. We found that they are present in the anterior and posterior aspects of testes. Furthermore, we cloned 2 kb prostate specific antigen promoter into pDsRed 2.1 plasmid and injected this plasmid DNA into single cell-stage zebrafish embryo with I-Sce1 to enhance transgenesis frequency and germline transmission. Larvae injected with PSA promoter-DSRed 2 constructs were screened three days post fertilization (dpf) for the expression of red fluorescence, which was observed in bilaterally arranged spots in gonads. We then used 5 dpf zebrafish larvae and IV-injected cells from four different cell lines expressing either GFP or RFP: two with stem cell phenotype RWPE-1-shDAB2IP (GFP), PZ-HPV7-shDAB2IP (GFP), and two as controls RWPE-1-shCon (GFP) and PC-3 (RFP). After two days, microscopy for green or red fluorescence signal revealed RWPE-1-shDAB2IP and PZ-HPV7-shDAB2IP cells bilaterally migrated to the yolk, i.e. the similar area where PSA promoter expression was found. This specific migration was not observed with RWPE-1-shCon and PC-3 cells lines. These same fluorescence reporter experiments were performed in parallel in 48 hr and 72 hr post fertilization (hpf) dechorinated larvae. We observed similar results in the 72 hpf larvae as were found in 5 dpf larvae but not in the 48 hpf larvae. Taken together, these results suggest that RWPE-1-shDAB2IP and PZ-HPV7-shDAB2IP cells have the homing receptors necessary for migrating to the same area in gonads. Understanding these homing mechanisms may be relevant for controlling the abnormal migration in metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4377. doi:10.1158/1538-7445.AM2011-4377
Abstract 1347: Genomic stress in antigen experienced T-lymphocytes
Authors: Shashank Patel, Madhusudhanan Sukumar, Douglas Palmer, Rahul Roychoudhari, Rabindra Roy, Andre Nussenzweig, Nicholas Restifo
Journal: Cancer Research (2015)

Abstract DNA damage response and repair (DDR) pathways are central to biological processes like hematopoietic stem cell maintenance, lymphocyte development and adaptive response to inflammation and cancer. However, the role of DDR in antigen experienced T-lymphocytes remains unclear. We studied the dynamics of DDR response during CD8+ T cell proliferation and differentiation. We found that DDR gene transcripts and gamma-H2AX, a marker for DDR pathway activation, are significantly up-regulated in CD8+ T cells expanded in-vitro and in-vivo. Next we aimed to determine the consequence of the activation of DDR pathways. Based on flow cytometry measurements of gamma-H2AX phosphorylation levels, we categorized CD8+ T cells into gamma-H2AXLo and gamma-H2AXHi cells. gamma-H2AXLo CD8+ T cells actively proliferate and produce cytokines, while gamma-H2AXHi CD8+ T cells lose their ability to produce cytokines, and undergo apoptosis. To define whether oxidative stress or replicative stress incurred in CD8+ T cell triggers this activation of DDR, we acutely treated cells with chemical agents and studied functional differences. These studies revealed that oxidative stress may be responsible for the inhibition of cytokine production and increase in cell death. Using Pmel transgenic p53-/- mouse model, we show that by deleting p53, a major signal modulator of DDR, the loss of cytokine production and cell death due to oxidative stress is reverted in CD8+ T cells. Currently, we are exploring the chemical and gene modification methods to manage oxidative stress in CD8+ T cells to improve T-cell based adoptive cell transfer therapies for cancer. Citation Format: Shashank Patel, Madhusudhanan Sukumar, Douglas Palmer, Rahul Roychoudhari, Rabindra Roy, Andre Nussenzweig, Nicholas Restifo. Genomic stress in antigen experienced T-lymphocytes. [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 1347. doi:10.1158/1538-7445.AM2015-1347
Abstract 3056: Mitochondrial DNA copy number and risk of second primary tumors in long-term breast cancer survivors
Authors: Miguel Santibanez, Alma Rodriguez, Michelle A. Hildebrandt, David W. Chang, Xifeng Wu
Journal: Cancer Research (2015)

Abstract Background. Mitochondria is constantly exposed to reactive oxygen species (ROS), an important factor in carcinogenesis. Altered mitochondrial DNA (mtDNA) copy number in peripheral blood has been associated with increased risks of several cancers, including breast cancer. However, the association of mtDNA copy number with clinical outcomes of breast cancer has not been reported. This study aimed to assess the association of mtDNA copy number with second primary tumors (SPT) in long-term breast cancer survivors. Methods. We measured mtDNA by quantitative PCR in patients in 68 long-term breast cancer survivors with SPT, 100 long-term breast cancer survivors without SPT and 97 newly diagnosed breast cancer cases. Cases with and without SPT were matched by years since diagnosis, age at time of sample collection and race. Differences between mtDNA copy number among groups were analyzed using the Wilcoxon rank sum test. Results. MtDNA copy number was significantly higher in long-term breast cancer survivors (either with SPT or not SPT) compared with newly diagnosed breast cancer patients (Mean (SD), 1.03 ± 0.25 vs 0.95 ± 0.27; p = 0.005). We did not observe significant differences of mtDNA copy number between long-term survivors with SPT and without SPT. However, in stratified analyses by epidemiological and clinical variables, we observed lower mtDNA copy number in HER2-positive long-term survivors with SPT than those without SPT (0.84 ± 0.13 vs 1.27 ± 0.44; p = 0.010) and in pre-menopause long-term survivors with SPT than those without SPT (0.95 ± 0.20 vs 1.06 ± 0.22; p = 0.034). A borderline significance of mtDNA copy number between SPT and non-SPT ER-negative long-term survivors was also noted (0.90 ± 0.17 vs 1.18 ± 0.41, p = 0.056). Conclusion. Higher mtDNA copy number was found in long-term breast cancer survivors compared to newly diagnosed cases. There were significant associations between lower mtDNA copy number and SPT in long-term breast cancer survivors who are HER2+ or are pre-menopause. These results indicate a role of mtDNA copy number in long-term breast cancer survivorship. Citation Format: Miguel Santibanez, Alma Rodriguez, Michelle A. Hildebrandt, David W. Chang, Xifeng Wu. Mitochondrial DNA copy number and risk of second primary tumors in long-term breast cancer survivors. [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 3056. doi:10.1158/1538-7445.AM2015-3056
Abstract 3796: Synergistic effect of targeted combination therapy in bladder cancer model using HSP90 inhibitors
Authors: Raju Chelluri, Piyush K. Agarwal, Leonard M. Neckers, Armine K. Smith
Journal: Cancer Research (2015)

Abstract Background In order to survive bladder cancer (BCa) cells deregulate key pathways - including the inhibition of apoptosis - while developing “oncogene addiction” to molecular chaperones such as Heat Shock Protein 90 (HSP90). While successful in vitro, monotherapies targeting such pathways have failed in clinical trials. We aim to show the superiority of combination therapy using proteostatic and targeted cytotoxic agents. We hypothesize that these combinations will synergize to increase cytotoxicity (CT) in BCa by amplifying the apoptosis via simultaneous activation of both intrinsic and extrinsic apoptotic pathways. Methods The proteostatic agents tested were the HSP90 inhibitor STA9090 (9090) and the proteasome inhibitor Marizomib (NPI). The cytotoxic agent used was a synthetic TRAIL ligand. These agents were tested in multiple ATCC BCa cell lines and the NCI patient tumor-derived BCa cell line UOBL 101 (UOBL). CT was determined via MTT assay. Mechanism of cytotoxic response was investigated using a series of immunoblots targeting the components of intrinsic and extrinsic apoptotic pathways and nuclear degradation proteins. All the assays were performed in triplicates for validation. Results 9090 (IC50 7.4-10 nM) was effective in all cell lines, as was NPI (IC50 10-20 nM). TRAIL caused 100% CT in UOBL (IC50 2.5 ng/mL, 95% CI [1.0, 7.0]) and a maximal 50% CT in T24, however the cytotoxicity of individual agents was not sustained. Combination effects of 9090 + TRAIL and NPI + TRAIL demonstrated an increase from 50% CT to 100% CT at the IC50 of both 9090 and NPI, and this effect was sustained over the course of the experiment. The increased cytotoxicity of combination therapy had corresponded to rapid cytoplasmic release of cytochrome c, additive increase in cleaved caspase 3 and caspase 8, with the corresponding increase in cleaved PARP and γ-H2ax. Conclusions Combination of a pro-apoptotic agent with a molecular chaperone or proteasome inhibitor holds promise in BCa therapyby affecting intracellular anti-apoptotic signaling and compromising efficient proteostasis in cancer cells lines, and should be investigated further. Citation Format: Raju Chelluri, Piyush K. Agarwal, Leonard M. Neckers, Armine K. Smith. Synergistic effect of targeted combination therapy in bladder cancer model using HSP90 inhibitors. [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 3796. doi:10.1158/1538-7445.AM2015-3796
The genetic and transcriptional basis of short and long term adaptation across multiple stresses in <i>Escherichia coli</i>
Authors: Violeta Zorraquino, Minseung Kim, Navneet Rai, Ilias Tagkopoulos
Journal: Molecular Biology and Evolution (2016)

Microbes exhibit short and long term responses when exposed to challenging environmental conditions. To what extent these responses are correlated, what their evolutionary potential is and how they translate to cross-stress fitness is still unclear. In this study, we comprehensively characterized the response of Escherichia coli populations to four abiotic stresses (n-butanol, osmotic, acidic, and oxidative) and their combinations by performing genome-scale transcriptional analysis and growth profiling. We performed an analysis of their cross-stress behavior which identified 15 cases of cross- protection and one case of cross vulnerability. To elucidate the evolutionary potential of stress responses to individual stresses and stress combinations, we re-sequenced E. coli populations evolved in those four environments for 500 generations. We developed and applied a network-driven method that integrates mutations and differential expression to identify core and stress-specific gene communities that are likely to have a phenotypic impact. Our results suggest that beyond what is expected from the general stress response mechanisms, cross-stress behavior arises both from common pathways, several including metal ion binding and glycolysis/gluconeogenesis, and stress-specific expression programs. The stress-specific dependences uncovered, argue that cross-stress behavior is ubiquitous and central to understanding microbial physiology under stressful conditions.
Clinical Outcome of IgM Amyloidosis (AL) Following Stem Cell Transplantation.
Authors: Morie Abraham Gertz, Martha Q. Lacy, Angela Dispenzieri, Suzanne R. Hayman, Shaji K. Kumar, Stephen M. Ansell, Michelle A. Elliott, Dennis A. Gastineau, David J. Inwards, Patrick B. Johnston, Ivana N. Micallef, Luis F. Porrata, Mark R. Litzow
Journal: Blood (2005)
PO65TAILORING HIGH GRADE GLIOMA MANAGEMENT IN THE ELDERLY
Authors: H. Georges, G. Critchley, M. Lynch, G. Walsh, A. Creak, J. Brock
Journal: Neuro-Oncology (2015)

INTRODUCTION: With the increased effectiveness of the MDM more elderly patients with a radiological diagnosis of high grade glioma (HGG) are being discussed. Collaboration with local acute oncology, medical and palliative services allows avoiding unnecessary transportation of patients with poor performance status (PS). To achieve this we introduced a specialized supportive letter to empower local teams to explain the rationale for recommending palliative care alone for patients with poor PS with an offer of a neuro-oncology appointment if the patient/family requested. We are presenting a further review of our management strategies during the year 2014. METHOD: Retrospective analysis of the management of elderly patients aged ≥70 with HGG based on radiological findings or histological analysis, who were referred to the Neurosciences MDM in 2014. The following information was gathered from MDM database: age, WHO PS, type of treatment, histology results including MGMT status, overall survival(OS). And verbal feedback obtained about supportive letters. RESULTS: 47 patients(50% increase comparing with 2012). Median age 78 yrs, PS (0-2)in 17 patients and (3-4)in 30 patients. 13 patients underwent surgery (8 debulking, 5 biopsy). Only 5 patients (post-op) were suitable for subsequent oncological treatment (2 had TMZ alone). 31 patients received palliative care only (Mean OS 2.3 months). 22 patients were not seen by neuro-oncology team(8 letters sent to local teams with satisfactory feedback). CONCLUSION: Patients with PS 3-4 would benefit from effective communication between MDT and local teams. On the other hand patients with PS 0-2 would benefit from multidisciplinary assessment prior to surgical intervention.
Is There a Role for ATRA in Combination to EPO in Lower Risk Myelodysplastic Syndrome? Preliminary Results of a Phase II Study.
Authors: L. Ades, H. Mohamed, D. Vassilief, E. Berger, B. Slama, N. Vey, R. Delarue, O. Beyne-Rauzy, A. Guerci, S. Cheze, X. Thomas, A. Stamatoullas, M. Gardembas, F. Bauduer, A. Kolb, M.C. Chaury, L. Legros, G. Damaj, F. Hamza, S. Vaultier, F. Dreyfus, P. Fenaux
Journal: Blood (2005)
Effectiveness, safety, and tolerability of oral morphine in patients with cancer.
Authors: P. Dwivedi
Journal: Journal of Clinical Oncology (2011)

e19527 Background: Pain is the most common symptom of cancer. Effective management of moderate to severe cancer pain in most cases requires treatment with opioid analgesics.The goal of cancer pain management is to improve the quality of life of patients. Methods: The aim of this study was to evaluate the Efficacy, Safety and Tolerability of oral morphine in cancer patients. In Indira Gandhi Regional Cancer Center, Raipur (C.G.) from Jan. 2003 to June 2006 1235 metastatic cancer patients were studied, out of which 600 patients were female of 635 patients were male. Age group of patients was 20 year to 75 year. Most of the patients included in this study presented with advanced cancer and required oral morphine for moderate to severe cancer pain (W.H.O. Step ladder 2 and 3). We use immediate release morphine because this is much cheaper, however and is as effective. A typical starting doses for immediate release oral morphine is 10 to 30mg every 3-4 hr. in patients not currently receiving opioids. When a patient is switching from another opioid (usually codeine) to morphine it is important to calculate the equianalgesic morphine dose. Results: There were 635 male patients (51.42%) and 600 female patients (48.58%). The mean age was 54 yr. The average time of use was 6.4 months. Mean initial and final pain score were 7.4 and 1.3 respectively. Severe toxicity was 0% and the most of the side effects was G.I. effects: Constipation (41.6%), Nausea/Vomiting (28.7%), C.N.S. side effects: sedation and myoclonus (21.3%), Respiratory depression (6.2%), urinary retention, Xerostomia and non-cardiogenic pulmonary edema (8.9%). Adjuvant drugs were used in 846 patients (68.50%) to control pain. Uncontrolled pain occurred in 146 patients (11.82%). Conclusions: Pain control was achieved in the majority of patients. Morphine showed a low toxicity profile with a high compliance rate. Side effects are manageable and are mainly G.I. effects (constipation). Economic reasons must be strongly considered in developing countries and immediate release morphine represents a good alternative option.
Abstract 5359: Antitumor efficacy of EC1456 in patient derived xenograft models of ovarian, endometrial, NSCLC and TNBC
Authors: Joseph A. Reddy, Alicia Bloomfield, Christina Taylor, Katherine Hargett, Melissa Nelson, Christopher Leamon
Journal: Cancer Research (2015)

Abstract EC1456, a potent folate-targeted tubulysin conjugate, is currently being evaluated in a phase 1 dose escalation study in patients with advanced solid tumors. To assist in upcoming cancer indication selection decisions for advanced trials, we tested EC1456 against eight patient-derived xenograft (PDX) cancer models. Thus, EC1456 was evaluated as a single agent or in combination with standard of care (SOC) treatments against two folate receptor (FR)-positive models each of ovarian, endometrial, non-small cell lung (NSCLC) and triple negative breast (TNBC) tumor models. Nude mice engrafted subcutaneously with PDX tumors received 4 μmol/kg/week EC1456 for two weeks, following a once a week (SIW) or two times a week (BIW) schedules, either alone or in combination with 15 mg/kg, SIW x 2 Paclitaxel (ovarian and endometrial), 1 mg/kg SIW x 2 eribulin mesylate (TNBC) or 15 mg/kg, SIW docetaxel (NSCLC). EC1456 alone demonstrated tumor growth suppression or stasis in most of the tumor models and significantly greater anti-tumor activity (including cures) with no detectable increase in toxicity when tested in combination with the SOC agents. Overall, EC1456 significantly augmented the growth inhibitory effects of SOC treatments against all four PDX cancer indications examined, thus lending support to future clinical development of this novel FR-targeted agent. Citation Format: Joseph A. Reddy, Alicia Bloomfield, Christina Taylor, Katherine Hargett, Melissa Nelson, Christopher Leamon. Antitumor efficacy of EC1456 in patient derived xenograft models of ovarian, endometrial, NSCLC and TNBC. [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 5359. doi:10.1158/1538-7445.AM2015-5359
QOL-27PREVALENCE OF CHANGES IN PERSONALITY AND BEHAVIOR IN ADULT GLIOMA PATIENTS: A SYSTEMATIC REVIEW
Authors: Hanneke Zwinkels, Linda Dirven, Thomas Vissers, Esther J.J. Habets, Maaike J. Vos, Jaap C. Reijneveld, Martin J. van den Bent, Martin J.B. Taphoorn
Journal: Neuro-Oncology (2015)

BACKGROUND: Gliomas are rare, with a dismal outcome and an obvious impact on quality of life, because of neurological, physical and cognitive problems, as well as personality and behavioral changes. These latter changes may affect the lives of both patients and their relatives in a profound way, but it is unclear how often this occurs and to what extent. METHODS: We performed a systematic review to determine the prevalence of changes in personality and behavior in glioma patients. Searches were conducted in PubMed/Medline, PsycINFO, Cochrane, CINAHL and Embase. Based on predetermined in- and exclusion criteria, papers were screened for eligibility. Information on the topics of interest were subtracted from the full-text papers: prevalence and used definition of personality and/or behavioral changes, impact, and tools used to measure these changes. RESULTS: The search yielded 9895 papers, of which 18 were found to be eligible; 9 qualitative and 9 quantitative studies. The reported prevalence rates of changes in personality and/or behavior varied from 8-67% in glioma patients, and was 100% in a bilateral thalamic case series. Moreover, these changes were associated with distress and a lower quality of life of both patients and informal caregivers. Methods of measurement of personality and behavioral changes differed considerably, as did the description of these changes. The terms ‘personality change’, ‘behavioral change’ and ‘cognitive or behavioral change’ were used interchangeably. CONCLUSION: Data on the prevalence of personality and behavioral changes are scarce, but present in a substantial number of glioma patients, with a profound impact. To determine the true prevalence of these changes, proper designed prospective studies are needed using proper definitions of personality and behavioral changes and validated measuring tools. Ultimately, these findings may result in improved supportive care of both patients and caregivers, during the disease trajectory.
Abstract 3383: Correlation of mutations detected in liquid and tissue biopsies
Authors: Douglas H. White, Douglas Horejsh, Molly Accola, William Rehrauer, Marjeta Urh
Journal: Cancer Research (2015)

Abstract Circulating cell-free DNA (ccfDNA) in plasma can be used to detect biomarkers that show great promise for diagnosis and monitoring of cancer, giving rise to the possibility of liquid biopsies that obviate the need for invasive tissue collection. The low concentration and highly fragmented nature of ccfDNA, coupled with the low frequency of potential oncogenic biomarkers, presents challenges and will require a purification method that is efficient and highly reproducible. Here we describe a method for purifying nucleic acids based on novel surface and binding chemistries. The combination of these two approaches allows for increased binding of fragmented DNA. The method can be partially automated to ensure highly reproducible results. Up to 4mls of plasma can be processed and eluted in as little as 15ul, giving DNA concentrations of 1-10ul. This greatly facilitates use in Next Generation Sequencing. Using the automated method, ccfDNA was purified from the plasma of 7 patients who had previously undergone surgical resection for malignancy. DNA was also purified from the FFPE malignant tissue off of slides, following macrodissection, from the same patients. NGS was used to interrogate both sample types for potentially oncogenic variants. Several laboratory developed tests, all including COLD-PCR, were also employed to verify the presence or absence of variants. The two types of samples showed excellent correlation on mutations, suggesting that use of a less invasive liquid biopsy has the potential to enable actionable mutation detection without using more invasive solid tumor biopsy means. Citation Format: Douglas H. White, Douglas Horejsh, Molly Accola, William Rehrauer, Marjeta Urh. Correlation of mutations detected in liquid and tissue biopsies. [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 3383. doi:10.1158/1538-7445.AM2015-3383