tbuckley/cabot-search huggingface dataset:
Bone marrow cellularity at day 14 is the most important predictive factor for response in patients with AML who require double‐induction chemotherapy: Analysis from a large, single institution experience
Authors: Patrick T. Griffin, Rami S. Komrokji, Kendra Sweet, Najla H. Al Ali, Eric Padron, Timothy E. Kubal, Alan F. List, Jeffrey E. Lancet
Journal: American Journal of Hematology (2016)

In patients with acute myeloid leukemia (AML), the presence of residual disease at day 14 after primary induction therapy warrants consideration of a second induction cycle. However, data to guide retreatment decisions in such patients are presently limited. Here, we retrospectively reviewed data from 176 patients with AML treated at our institution with a second induction chemotherapy regimen because of day 14 residual disease. Clinical variables and nadir bone marrow features were assessed for correlations with complete remission (CR) and overall survival (OS). In our patient group, 59% achieved CR after a second induction course. Median OS for the entire group was 12.40 months (95% CI, 9.90-14.90) but 19.07 months (95% CI, 13.13-25.01) for those who attained a CR. Nadir marrow hypocellularity (P < 0.001) at day 14, absolute blast reduction of >50% (P = 0.030), and de novo disease status (P = 0.018) were significantly correlated with CR achievement after re-induction. Marrow hypocellularity at day 14 was the most significant predictor of CR on multivariate analysis (P < 0.001). Nadir marrow features did not independently correlate with OS when accounting for CR status. Re-induction was successful in achieving CR in most patients. Study patients who did not achieve CR were more likely to have nonhypocellular marrows.
Effect of radiation on cytokines, MMP-1 and type I collagen mRNA expressions in human gingival fibroblasts.
Authors: G. Yavas, C. Yavas, B. Bozkurt, O. Ata, S. Hakki
Journal: Journal of Clinical Oncology (2011)

e16034 Background: Oral mucositis is an acute injury to the mucosal lining of the head and neck region associated with radiation therapy (RT). In this study, we aimed to elucidate the effects of radiation on the proliferation of gingival fibroblasts and proinflammatory cytokines and matrix metalloproteinase-1 (MMP-1), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and type I collagen (COL I) mRNA expressions of gingival fibroblasts. Methods: Gingival fibroblasts were isolated from human gingival connective tissue of systemically healthy individuals. These cells were treated with radiation dosages as follows; control group (untreated), 0.5 Gry, 1 Gry, 2 Gry, 4 Gry, 6 Gry, and 8 Gry. RT was applied in the form of a single dose which was applied with linac 6 MV photon beams. Cell proliferation was determined by counting cells at 24 and 48 hrs. Total RNA was isolated at 24 hours after radiation. Expression of interleukin (IL)-1 beta, IL-6, IL-8 and MMP-1, TIMP-1 transcripts in HGFs was determined by quantitative PCR (QPCR) analysis. Morphology of gingival fibroblasts was evaluated using inverted microscope after different dosages of radiation. For proliferation experiments and gene expressions, the statistical analysis used was one-way analysis of variance (ANOVA) and Turkey HSD multiple comparison tests. Results: Radiation decreased cell proliferation (p<0.05) compared to the control group. Expression of IL1beta, IL-6 and IL-8 was stimulated at higher dosage (8 Gry) of radiation (p<0.001) (figure 1). In parallel, MMP-1, and TIMP-1 mRNA expressions were elevated in response to highest dosage of radiation (p<0.001) (figure 2). Radiation suppressed COL I mRNA expression in response to all dosages at 24 hrs (p<0.001). Conclusions: These findings demonstrated that radiation even in a single dose regulates behavior of gingival fibroblasts. Radiation-induced inflammatory characteristics of gingival fibroblasts could potentially lead to a disruption of oral mucosa. Results of this study clarify the possible mechanisms of radiation induced oral mucositis in radiation treated cancer patients.
GATA-1-Specific Coactivator MED1/TRAP220, Transcriptional Mediator Subunit, Mediates Erythroid Differentiation in K562 Erythroleukemia Cells.
Authors: Tomoya Minami, Osamu Horie, Kana Inoue, Sawako Toji, Norinaga Urahama, Mitsuhiro Ito
Journal: Blood (2008)
Lenalidomide Shuts Down the Translational Machinery in Multiple Myeloma Cells Resulting in Down-Regulation of Critical Transcription Factors Such as C/EBPβ and IRF4.
Authors: Shirong Li, Rekha Pal, Deborah L Galson, Peter H Schafer, Hongjiao Ouyang, Markus Y Mapara, Suzanne Lentzsch
Journal: Blood (2009)
105. Enhanced Oncolytic Activity Mediated by a Novel Human Adenovirus Type 6 Based Vector
Authors: Johannes Doerner, Wenli Zhang, Philip Boehme, Anja Ehrhardt
Journal: Molecular Therapy (2016)

Most existing oncolytic adenoviruses (AdV) are based on human AdV type 5 (hAdV-5). Clinical efficacy of hAdV-5 based oncolytic viruses is limited by variable expression levels of coxsackie- and adenovirus receptor (CAR) in different tumor cells and insufficient replication rates. Additionally, high prevalence of neutralizing antibodies against hAdV-5 resulting in lower efficiency makes hAdV-5 a less suitable candidate for systemic application. Recent studies have highlighted human adenovirus type 6 (hAdV-6) as a promising candidate for oncolytic and vaccine vectors. Thus, development of novel oncolytic AdV based on hAdV-6 may help overcoming these limitations. We further hypothesised that oncolytic efficacy of the candidate virus can be augmented by expression of RNAi suppressor protein P19 (Lecellier et al., Nature 2005) as has been shown previously for hAdV-5 (Rauschhuber et al, Sci. Rep. 2013). Here we aim at evaluating a novel hAdV-6-based, p19-containing oncolytic AdV as novel candidate for oncolytic applications in different tumour cell lines. We cloned a P19-containing hAdV-6 based virus (hAdV-6FP19) by a novel seamless recombineering technique (Zhang et al, unpublished). In order to allow P19 expression from the adenoviral vector genome, the P19 cDNA was fused via an internal ribosome entry site (IRES) to the late fiber gene. After release of the respective recombinant adenoviral genomes from plasmids containing the complete DNA molecule, linearized viral DNA was transfected into HEK293 cells for virus reconstitution. After initial amplification steps which were monitored by virus specific PCRs upscaling and virus purification using cesium-chloride density-gradient ultracentrifugation was performed. Rescue and amplification efficiencies were comparable to commonly used hAdV-5 based vectors. Various cancer cell lines from different origin were used to perform oncolysis assays. This included A549 (lung carcinoma), HCT 116 (colon carcinoma), Hela (cervical carcinoma) and Huh7 (hepatocellular carcinoma) cells which were infected with hAdV-6FP19, hAdV-6 and hAdV-5 at various multiplicities of infection (MOI). 2-3 days after infection cells were fixed and stained with methylene blue. We observed significantly higher cell lysis (up to 100-fold) for hAdV-6FP19 infected cells as compared to hAdV-5 and 6 at identical MOIs. Higher cell lysis rates for hAdV-6FP19 compared to wildtype virus were present in all evaluated cell lines, suggesting significantly enhanced oncolytic potential for hAdV-6FP19. In total we believe that hAdV6-based vectors hold great promise for oncolytic applications and that their oncolytic effectiveness can be further improved by RNAi-suppression.
Re-assessment of surgical breast cancer quality indicators by the Florida Initiative for Quality Cancer Care (FIQCC) consortium.
Authors: Christine Laronga, Jhanelle Elaine Gray, Erin Siegel, Ji-Hyun Lee, William J. Fulp, Paul B. Jacobsen
Journal: Journal of Clinical Oncology (2012)

84 Background: In 2006, the FIQCC (comprised of 11 practice sites) initiated a comprehensive review of quality of care specific to breast cancer based on QOPI/NCCN/ACOS and panel consensus quality indicators. Feedback on indicator performance was provided to participating practices in 2007 to encourage quality improvement efforts. Re-assessment of adherence to the same performance indicators was conducted in 2009. Methods: Chart reviews were conducted for breast cancer patients (pts) seen by a medical oncologist at FIQCC sites in 2006(n=602) and 2009(n=636) Quality indicators included: 1) presence/completeness of pathology report; 2) documentation of surgery type; 3) documentation of sentinel lymph node biopsy (SLNB) and if SLNB positive documentation of a complete axillary node dissection; and 4) mammogram usage post surgery. Statistical comparisons of 2006 and 2009 data were performed using the Pearson chi-square exact test based on Monte Carlo estimation. Results: The median age of pts (99% female) was 60 years (range 24-94). Compared to 2006 data, improvements were made in specimen orientation (69%-2006, 78%-2009; p=0.001) and inking of margins (89%-2006, 96%-2009; p=&lt;0.001). In clinical node negative N 0 pts, SLNB was performed in 87%, up from 82%-2006 (p=0.035). Of the pts with a metastatic SLNB, 86% went on to have a complete axillary node dissection, but not statistically significant compared to 79% in 2006 (p=0.10). Compliance continues to be highly variable across practice sites with obtaining a mammogram within 14 months of surgery (79%) (p=0.002); but the range narrowed: 26%-98% (2006) and 56%-92% (2009). Significant variances also continued in 2009 across practice sites for margin orientation (p&lt;0.001), inking of the margins (p=0.04), and performance of SLNB (p&lt;0.001). Conclusions: The FIQCC identified quality improvement needs in multiple aspects of breast cancer care. Improvements in margin orientation/inking, use of SLNB and follow-up mammograms after definitive surgery made over the course of this initiative speak to the benefits of continual re-assessment of adherence to performance indicators to guide quality improvement.
Abstract 947: An antibody drug conjugate (ADC) directed to lymphocyte antigen 6 complex, locus E (LY6E) delivers targeted chemotherapy to a wide range of solid tumor malignancies
Authors: Jyoti Asundi, Lisa Crocker, Jarrod Tremayne, Paul Polakis, Ron Firestein
Journal: Cancer Research (2015)

Abstract Chemotherapies are limited by a narrow therapeutic index resulting in suboptimal exposure of the tumor to the drug and acquired tumor resistance. One approach to overcome this is through Antibody Drug Conjugates (ADCs); that facilitate greater potency via target specific chemotherapy delivery. In this study, we used a bioinformatics approach to identify Lymphocyte antigen 6, locus E, (LY6E), an interferon-inducible glycosylphosphatidylinositol (GPI)-linked cell membrane protein, as a promising ADC target. Immunohistochemical analysis revealed LY6E was overexpressed in a number of tumor types, such as, breast, including triple negative breast cancer, lung, gastric, ovarian, pancreatic and head/neck carcinomas. Characterization of the endocytic pathways for LY6E revealed rapid uptake of the LY6E specific antibody into cells leading to lysosomal accumulation. Consistent with this, a LY6E specific ADC inhibited in vitro cell proliferation and produced durable tumor regression in vivo in high LY6E expressing cancers. Our results identify LY6E as a highly promising molecular ADC target for a variety of solid tumor types with current unmet medical need. Citation Format: Jyoti Asundi, Lisa Crocker, Jarrod Tremayne, Paul Polakis, Ron Firestein. An antibody drug conjugate (ADC) directed to lymphocyte antigen 6 complex, locus E (LY6E) delivers targeted chemotherapy to a wide range of solid tumor malignancies. [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 947. doi:10.1158/1538-7445.AM2015-947
Abstract 13423: Sleep Disruption is Associated With Incident Atrial Fibrillation Independent of Obstructive Sleep Apnea
Authors: Matthew A Christensen, Shalini Dixit, Isaac R Whitman, Gregory Nah, Thomas A Dewland, Eric Vittinghoff, Kenneth J Mukamal, Susan Redline, John A Robbins, Anne B Newman, Sanjay R Patel, Jared W Magnani, Bruce M Psaty, Susan R Heckbert, Jeffrey E Olgin, Mark J Pletcher, Gregory M Marcus
Journal: Circulation (2016)

Introduction: Obstructive sleep apnea (OSA) is an established risk factor for atrial fibrillation (AF), but the mechanism is unknown. Repeated hypopneas may induce mechanical stress but OSA also causes poor sleep which has been linked to other CVD. We sought to determine if sleep disruption independent of OSA is associated with AF. Methods: We compared sleep quality to AF in three population-based cohorts. (1) In the Health eHeart Study (HeH), an internet-based cohort study, we compared self-reported frequent nighttime awakening (waking at night ≥ 3x / week) to prevalent AF using logistic regression. (2) In the Cardiovascular Health Study, (CHS) we used Cox proportional hazards models to assess self-reported frequent nighttime awakening at baseline as a predictor of incident AF. (3) Last, we used statewide medical records in the California Healthcare Cost and Utilization Project (C-HCUP) from 2005 to 2009 to compare the diagnosis of insomnia to incident AF, again with Cox proportional hazards models. Results: Sleep disruption was associated with prevalent AF (HeH) and incident AF (CHS, C-HCUP) before and after adjustment for OSA and other potential confounders ( Figure ). (1) In HeH, 553/4603 (12%) had AF, and frequent nighttime awakening was associated with increased odds of AF. (2) In CHS, over a median 11.6 years (IQR 6.2 - 16.4) of follow-up 1593 (28%) developed AF; frequent nighttime awakening was associated with increased risk of incident AF. (3) Among 13,967,949 patients in C-HCUP over the 5-year study period, of which 375,318 (3%) developed AF over a median of 3.8 years (IQR 1.8 - 4.3), insomnia was associated with an increased risk of incident AF. Conclusions: Sleep disruption was associated with an increased risk of prevalent and incident AF after adjustment for OSA and other confounders in 3 diverse cohorts. Factors inherent to sleep may be important in AF pathogenesis and sleep quality may therefore be a modifiable risk factor for AF.
Abstract 2102: TBX2 promotes rhabdomyosarcoma (RMS) tumorigenesis by repression of PTEN expression
Authors: Bo K. Zhu, Judith K. Davie
Journal: Cancer Research (2015)

Abstract RMS is most common soft tissue sarcoma in children. We previously identified TBX2 as an oncogene and showed that TBX2 is required for tumor formation. Here, we identified the tumor suppressor PTEN as a novel target of TBX2 in RMS and normal muscle. PTEN, which regulates the PI3K-AKT pathway, is repressed in RMS. Our work shows that TBX2 functions to regulate PTEN expression and thus, PI3K-AKT signaling, to enhance the malignancy of RMS tumors. Both quantitative real time PCR and western blot assays were used to assay PTEN expression at the level of mRNA and protein respectively. Immunofluorescence staining was performed to assay the protein expression in human RMS tumor samples. Muscle tissue slides of proliferating myoblasts were assayed by co-immunofluorescence staining, and the proliferating myoblasts were induced by activating satellite cells with cardiotoxin induced muscle damage. Reporter constructs for luciferase assay were based on PTEN promoter. Chromatin immunoprecipitation (ChIP) assays were used to detect protein binding on gene promoters. Xenograft assays were conducted to assay TBX2 function in tumor malignancy. We have found that PTEN was up-regulated upon muscle differentiation, but little expression of PTEN was observed in RMS cells. Although TBX2 was expressed in proliferating myoblasts, it was highly down-regulated upon myogenic differentiation. Human RMS tumor samples showed a down-regulation of PTEN and an up-regulation of TBX2 compared with normal tissues. Over-expression of TBX2 repressed PTEN expression in both C2C12 myoblasts and 10T1/2 fibroblasts. Either depletion of TBX2 or a dominant negative TBX2 increased PTEN expression in RMS cells. Luciferase assays confirmed the regulation of PTEN by TBX2 and ChIP assays demonstrated that TBX2 recruited HDAC1 to the PTEN promoter for repression. The role of HDAC1 in repression of PTEN was confirmed by treatment with HDAC inhibitors, which abrogated the repression of PTEN by TBX2. This work demonstrates that the high expression of TBX2 in RMS is involved in the activation of PI3K-AKT signaling pathway by repressing PTEN, underlying the oncogenic function of TBX2 in tumor cells. Citation Format: Bo K. Zhu, Judith K. Davie. TBX2 promotes rhabdomyosarcoma (RMS) tumorigenesis by repression of PTEN expression. [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 2102. doi:10.1158/1538-7445.AM2015-2102
Geriatrics, oncology, and palliative care for patient-tailored treatment: A Brookdale experience.
Authors: S. G. Naik, T. L. Dumlao, M. Kalavar, W. Steier
Journal: Journal of Clinical Oncology (2007)

17028 Background: Patients over 75 years of age are particularly underrepresented in clinical trials. Measures have been used to help characterize the functional age of a patient, to optimize treatment decisions and stratify outcomes, based on factors other than chronological age. The purpose of this study was to evaluate if palliative and social issues influence decision-making in this older population. Methods: The geriatrics oncology patients’ consults from July 2005 to December 2006 were reviewed. In addition to geriatric and oncology tools, palliative measures such as advanced directives, DNR status and social support were incorporated. Results: 89 pts with mean age 80.3 years (range 72–91) and AJCC Stages I (3.3%), II (16.8%), III (28%), and IV (46%) across various malignancies were included. Of the study population, 86% of patients were &gt; 75 years of age, 55% were women, and 75% were widowed; 64% were African- American and 20% were Hispanic. Interestingly, 14 patients (15.7%) had diagnosis of previous cancer (6 breast, 6 prostate). Performance status (KPS and ECOG), activities of daily living (ADL) and instrumental activities of daily living (IADL) scales were assessed. 38.2% had KPS&gt;70, and 31.5% had KPS&lt;40. 22.4% were also independent for instrumental activities of daily living. 33% patients had advanced directives (including DNR status) at diagnosis. Consent was signed by patients themselves in 56% of cases. Social issues included: 22.4% were in NH, 10.11% without social support, 21.3% with falls, and 41.6% with depression in the GDS. Co-morbidities included HTN in 50%, dementia in 19.1%, and multiple medical problems in 21.3% patients. 30.33% pts received aggressive treatment, while19.1% were referred to hospice, with 50% requiring palliation. Pain was the main symptom that needed palliation in 48.3% patients. Supportive care included use of growth factors 24.7% and erythropoietin 48.3%. Conclusions: Social support, advanced directives, consent were the main issues even in patients with good performance status and absence of major co morbidities. Strategies to increase participation of good performance status elderly patients in geriatric clinical trials should include pain and palliative care issues. No significant financial relationships to disclose.
MEMBRANE VOLTAGE AND ION CURRENTS OF GLOMERULAR VISCERAL EPITHELIAL-CELLS IN CULTURE (GECC) AND IN THE INTACT GLOMERULUM (GECG)
Authors: J Gloy, A Henger, W Coers, M Bleich, Kg Fischer, R Greger, P Schollmeyer, H Pavenstadt
Journal: Journal of the American Society of Nephrology (1995)
Abstract 2259: Requirement for BUB1B in tumor progression of lung adenocarcinoma
Authors: Honglin Chen, James Lee, Noelyn M. Kljavin, Benjamin Haley, Anneleen Daemen, Yuxin Liang, Leisa Johnson
Journal: Cancer Research (2015)

Abstract Lung adenocarcinoma is often discovered as metastatic disease with very poor prognosis. However, much remains unknown about the mechanisms of lung adenocarcinoma tumor progression. In this study we showed that knockdown of BUB1B, a critical mitotic checkpoint protein, significantly inhibited anchorage-independent growth of lung adenocarcinoma cell lines. In allograft and tail vein mouse model studies, BUB1B suppression inhibited primary tumor growth and reduced metastasis to the lung and lymph nodes, resulting in prolonged survival in both tumor prevention and tumor intervention settings. Mechanistic studies revealed that BUB1B knockdown sensitized cells to anoikis. The N-terminal region of BUB1B was required for its functions in both anchorage-independent growth and anoikis resistance, whereas the kinase domain was less critical. Overexpression of BUB1B is associated with disease progression and poor survival in human lung adenocarcinoma patients. Collectively, these data reveal a novel function for BUB1B in mediating anchorage-independent survival and growth, thereby facilitating lung adenocarcinoma dissemination during metastasis. Thus, targeting BUB1B could provide potential therapeutic benefit in suppressing metastasis and prolonging survival in lung adenocarcinoma patients. Citation Format: Honglin Chen, James Lee, Noelyn M. Kljavin, Benjamin Haley, Anneleen Daemen, Yuxin Liang, Leisa Johnson. Requirement for BUB1B in tumor progression of lung adenocarcinoma. [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 2259. doi:10.1158/1538-7445.AM2015-2259
Inhibition by Multifunctional Magnetic Nanoparticles Loaded with Alpha-Synuclein RNAi Plasmid in a Parkinson's Disease Model
Authors: Shuiqin Niu, Ling-Kun Zhang, Li Zhang, Siyi Zhuang, Xiuyu Zhan, Wu-Ya Chen, Shiwei Du, Liang Yin, Rong You, Chu-Hua Li, Yan-Qing Guan
Journal: Theranostics (2016)

Lewy bodies are considered as the main pathological characteristics of Parkinson's disease (PD). The major component of Lewy bodies is α-synuclein (α-syn). The use of gene therapy that targeting and effectively interfere with the expression of α-syn in neurons has received tremendous attention. In this study, we used magnetic Fe