tbuckley/cabot-search huggingface dataset:
Abstract 1527: Urinary miRNAs as predictors of tumor metastasis in localized patients with clear cell renal cell carcinoma: a pilot study
Authors: Xiang Shu, Michelle AT Hildebrandt, Rodolfo Borges dos Reis, Yuanqing Ye, Jian Gu, Christopher G. Wood, Xifeng Wu
Journal: Cancer Research (2016)

Abstract Introduction: 25-50% of localized renal cell carcinoma (RCC) patients will eventually develop metastasis which has a dramatic adverse effect on prognosis following treatment. Unfortunately, reliable biomarkers predicting RCC metastasis are still lacking. MicroRNAs (miRNAs) are important regulators for vital biological processes in humans. Urine miRNAs(UmiRNAs) present promising potential as biomarkers for diagnosis of urological cancers. However, no study has assessed the predictive value of UmiRNAs for RCC metastasis. Materials and Methods: We prospectively collected pre- and post-surgery urine samples from 117 patients with localized clear cell RCC (ccRCC,T1-3 N0/x M0). UmiRNAs were extracted and purified from 250 μl urine supernatants and measured using RT-PCR. Relative quantifications (RQ) of 137 selected miRNAs were calculated by 2−ΔΔct method. The ratio of post/pre RQs were tested for the association with distant metastasis using multivariable Cox regression models. Results: More than half of the patients were diagnosed at pT3 (53%) or grade III-IV (69%). Twenty-two patients (18.8%) had metastasis during a mean follow-up of 73 months. The levels of 34 UmiRNAs were significantly changed after nephrectomy (p&amp;lt;0.05, 29 of 34 significantly reduced). The 50% or more reduced post-nephrectomy levels of five UmiRNAs (miR-191-5p, miR-324-3p, miR-186-5p, miR-93-5p, and miR-30b-5p) independently conferred a 2- to 4-fold increased risk of metastasis with miR-191-5p being the most significant one (hazard ratio [HR] = 4.16, 95% confidence interval [CI] = 1.38-12.58, p = 0.011). Stratified analyses by stage and Fuhrman grade revealed that the associations were most profound in pT3 patients for miR-191-5p, miR-324-3p, and miR-186-5p. Ingenuity pathway analysis showed that the predicted target genes of these five UmiRNAs were enriched in cell survival and proliferation networks. Conclusion: Our study suggests that urinary miR-191-5p, miR-324-3p, and miR-186-5p are potential biomarkers for the prediction of metastasis in localized, particularly pT3 ccRCC patients after nephrectomy. These findings may help improve individualized patient management in the clinic. Citation Format: Xiang Shu, Michelle AT Hildebrandt, Rodolfo Borges dos Reis, Yuanqing Ye, Jian Gu, Christopher G. Wood, Xifeng Wu. Urinary miRNAs as predictors of tumor metastasis in localized patients with clear cell renal cell carcinoma: a pilot study. [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 1527.
Abstract 2917: Therapeutic targeting of the mitochondria: An evaluation of the transcriptional link between the antioxidant response and autophagy
Authors: Kaytee L. Pokrzywinski, Francesca Mascia, V. Ashutosh Rao.
Journal: Cancer Research (2016)

Abstract Mitoquinone (MitoQ), a mitochondrially targeted chemotherapy induces autophagy via excess reactive oxygen species (ROS) production. Elevations in ROS stimulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in breast cancer cell lines. Nrf2 is a nuclear transcription factor that activates the antioxidant response element when under oxidative stress. The aim of this study was to evaluate transcriptional and protein changes associated with Nrf2 activation to identify potential links between oxidative stress, autophagy and cell death. By suppressing Nrf2 and its targeted antioxidant enzymes we should induce elevated ROS levels, which can thereby alter cellular homeostasis and impact the ultimate fate of cancer cells. In the breast cancer cell line MDA-MB-231 RNA was extracted after 24 hours of Nrf2 or non-target pool (NTP) silencing and 18 hours of MitoQ treatment. RNA was sequenced using an Illumina HiSeq and differential expression was analyzed using DESeq in the statistical program R. To avoid bias, raw read counts were filtered to remove low counts possibly due to constraints of the instrumentation. To validate efficient silencing of Nrf2 we confirmed that Nrf2 transcript levels decreased and that there were observed reductions in transcripts containing the Nrf2 transcriptional promoter, the antioxidant response element (ARE) including FTH1, FTL, HMOX1, SRXN1, TXNRD1, NQO1, GCLC, GCLM, GSR and SQSTM1. From there we validated RNAseq data with qPCR using 25 random transcripts and found significant positive correlation between the two methods. Comparisons were first made between the MitoQ and DMSO treatment by silencing (NTP or Nrf2). 2775 genes were differentially expressed (DE) for MitoQ vs DMSO NTP siRNA and 1869 genes were DE for MitoQ vs DMSO Nrf2 siRNA both at an α &amp;lt; 0.05 and Log2 fold change cut off &amp;gt; |1|. We then compared the degree of overlap in DE gene lists between the NTP and Nrf2 siRNA comparisons to identify genes affected only by Nrf2 silencing in combination with MitoQ treatment. 1405 mRNAs were common between silenced and non-silenced sample sets, only 464 mRNAs were due to Nrf2 silencing alone. We are currently performing pathway analysis on these transcripts to determine the role of Nrf2 silencing with redox-active therapies. We are also evaluating autophagic protein levels at later time points, 24 to 48 hours, to further evaluate the potential signaling between oxidative stress and the autophagic response driven by Nrf2. Citation Format: Kaytee L. Pokrzywinski, Francesca Mascia, V. Ashutosh Rao. Therapeutic targeting of the mitochondria: An evaluation of the transcriptional link between the antioxidant response and autophagy. [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 2917.
Abstract 4293: Combination of hepatocyte growth factor, genistein and daidzein concentrations as a biomarker for gastric cancer risk: A nested case-control study
Authors: Jieun Jang, Yunji Hwang, Choonghyun Ahn, Kwang-Pil Ko, Keun-Young Yoo, Sue K. Park
Journal: Cancer Research (2016)

Abstract Backgrounds: Hepatocyte growth factor (HGF) induces ERK pathway which is associated with carcinogenesis by promoting cell proliferation. Inhibition of ERK signal transduction pathways by genistein, one of the isoflavones, has been reported by several in vitro studies. Therefore, gastric cancer risk by HGF and isoflavone concentrations was evaluated in this study. Methods: Nested case-control study with 93 gastric cancer cases and 1:1 matched controls was conducted within the Korean Multi-center Cancer Cohort (KMCC). HGF and ISF (genistein, daidzein, equol) concentrations in plasma were measured with enzyme-linked immunosorbent assay and time-resolved fluoroimmunoassay, respectively. Odds ratios (ORs) and 95% confidence intervals (95% CIs) on gastric cancer risk according to HGF and ISF level was calculated using conditional logistic regression models. Results: Compared to the group with low level of HGF (&amp;lt;315pg/mL) and high level of genistein (≥212.5nmol/L), the group having high level of HGF and lower level of genistein was associated with increased gastric cancer risk (OR = 5.08, 95% CI = 1.39-18.57). Elevated gastric cancer risk in the subjects having high HGF level and low daidzein level than subjects with low HGF and high daidzein levels was also shown (OR = 3.67, 95% CI = 1.18-11.45). There was significant interaction between HGF and genistein levels on gastric cancer was found (p for interaction&amp;lt;0.01). Continual increase in gastric cancer risk according to the counts of risky status by HGF, genistein, and daidzein levels was found (p for trend = 0.03). Conclusion: Our study suggests that combination of HGF, genistein and daidzein concentrations has potential as a biomarker for gastric cancer risk. Citation Format: Jieun Jang, Yunji Hwang, Choonghyun Ahn, Kwang-Pil Ko, Keun-Young Yoo, Sue K. Park. Combination of hepatocyte growth factor, genistein and daidzein concentrations as a biomarker for gastric cancer risk: A nested case-control study. [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 4293.
Abstract 2952: Generation and molecular profiling of drug-resistant cancer cell lines
Authors: Fang He, Pengwei Pan, Zengjin Yuan, Jingqi Huang
Journal: Cancer Research (2016)

Abstract Drug resistance is the main cause of ineffective chemotherapy in patients. Many cancers respond initially well to therapy but eventually the cancer recurs as drug-resistant disease leading to the patient death. Therefore, a better understanding of the molecular basis of the drug resistance is warranted in order to elucidate the mechanisms and markers underlying this drug-resistant phenotype In this study, we aimed to generate and characterize a panel of drug resistant cancer cell lines, providing a valuable tool with which to investigate the molecular pathways and putative markers that may be associated with this resistance phenotype in cancer. Citation Format: Fang He, Pengwei Pan, Zengjin Yuan, Jingqi Huang. Generation and molecular profiling of drug-resistant cancer cell lines. [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 2952.
Review: NAATs diagnose<i>C difficile</i>; vancomycin improves cure, and fidaxomicin reduces recurrence
Authors: Fred Arthur Zar
Journal: Annals of Internal Medicine (2016)

Source Citation Butler M, Olson A, Drekonja D, et al. Early diagnosis, prevention, and treatment of Clostridium difficile: Update. Comparative Effectiveness Review No. 172. AHRQ Publication No. 16-EHC012-EF. Rockville, MD: Agency for Healthcare Research and Quality; March 2016.
A Phase I Pilot Study of Bystander Vaccine and Lenalidomide Immune Augmentation In Patients with Myelodysplastic Syndrome (MDS)
Authors: Eric Padron, Rami S. Komrokji, Jeffrey E. Lancet, Alan F. List, Sophie Dessureault, Scott Antonia, Jamil Ahmed, Shiddhi Patel, John Powers, Fanqi Bai, Eduardo M. Sotomayor, P.K. Epling-Burnette, Javier Pinilla-Ibarz
Journal: Blood (2010)
Comparison of Sterile vs Nonsterile Gloves in Cutaneous Surgery and Common Outpatient Dental Procedures
Authors: Jerry D. Brewer, Alexandra B. Gonzalez, Christian L. Baum, Christopher J. Arpey, Randall K. Roenigk, Clark C. Otley, Patricia J. Erwin
Journal: JAMA Dermatology (2016)

Whether the use of sterile vs nonsterile gloves in outpatient cutaneous procedures affects the rate of postoperative wound infection is unknown.To explore rates of surgical site infection (SSI) with the use of sterile vs nonsterile gloves in outpatient cutaneous surgical procedures.This systematic review and meta-analysis identified studies from Ovid MEDLINE (1946 to present), Ovid Cochrane Central Register of Controlled Trials (1991 to present), Ovid EMBASE (1988 to present), EBSCO Cumulative Index to Nursing and Allied Health Literature (1980 to present), Scopus (1996 to present), and Web of Science (1975 to present).Studies with information on sterile vs nonsterile gloves in outpatient surgical procedures were retrieved. Only randomized clinical trials and comparative studies were included for final analysis.Data of trial design, surgery characteristics, and outcomes from published manuscripts and unpublished data were independently extracted.Randomized clinical trials were considered high quality if randomization, allocation concealment, blinding, and follow-up completeness were appropriate. Relative risk and 95% CIs were derived for postoperative wound infections.Fourteen articles met eligibility and inclusion criteria for systematic review; they included 12 275 unique patients who had undergone 12 275 unique outpatient procedures with sterile or nonsterile gloves and had follow-up regarding SSI. With the exclusion of 1 single-arm observational study of 1204 patients, 11 071 patients from 13 studies remained in the meta-analysis. Of these, 228 patients were documented as having postoperative SSI (2.1%), including 107 of 5031 patients in the nonsterile glove group (2.1%) and 121 of 6040 patients in the sterile glove group (2.0%). Overall relative risk for SSI with nonsterile glove use was 1.06 (95% CI, 0.81-1.39).No difference was found in the rate of postoperative SSI between outpatient surgical procedures performed with sterile vs nonsterile gloves.
Abstract CT120: Radiotherapy in pediatric patients with atypical teratoid rhabdoid tumor of the central nervous system
Authors: Melissa Frick, Jane Minturn, Yi-Mei Li, Christine Hill-Kayser
Journal: Cancer Research (2016)

Abstract Atypical teratoid/rhabdoid tumor (ATRT) of the CNS is a rare, highly malignant tumor of early childhood. Current protocols favor multimodality treatment, but practice guidelines differ with regard to radiotherapy. The aim of this study was to evaluate outcomes and prognostic factors in pediatric ATRT receiving multimodality treatment including postoperative radiation. Pediatric subjects with CNS ATRT treated at our institution between 2000 and 2014 were evaluated. Kaplan Meier method was used to estimate progression free survival (PFS) and overall survival (OS) over time and log-rank tests were used to examine associations of demographic and treatment factors with PFS and OS. 20 pediatric subjects (median age 23.5 months; range 4-99 months) with CNS ATRT treated at our institution between 2000 and 2014 were retrospectively evaluated. All underwent surgical resection, adjuvant radiotherapy, and aggressive multi-agent chemotherapy. PFS at 1-year was 63.3% (95% CI, 38.1% - 80.6%) and 2-years was 46.1% (95% CI, 22.9% - 66.5%). OS at both 1- and 2-years was 73.0% (95% CI, 46.7% - 87.8%). Infratentorial disease, lack of metastatic disease at diagnosis, and gross total tumor resection were identified as beneficial prognostic factors in PFS and OS. Progressive disease after radiation was identified as a poor prognostic factor in OS. Radiation modality (proton versus x-ray) did not affect disease-related outcomes. Modern treatment for ATRT with aggressive multimodality therapy including radiotherapy results in a significant portion of subjects with long-term disease control. Prognosis appears to be improved in subjects with localized, completely resected disease. Citation Format: Melissa Frick, Jane Minturn, Yi-Mei Li, Christine Hill-Kayser. Radiotherapy in pediatric patients with atypical teratoid rhabdoid tumor of the central nervous system. [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 CT120.
Abstract 2097: Translating a mutant p53 reactivating drug (ZMC1) in murine pancreatic cancer models
Authors: Xin Yu, Ashley T. Tsang, Tracy Withers, John Gelleran, David Augeri, S. David Kimball, Darren R. Carpizo
Journal: Cancer Research (2016)

Abstract Pancreatic cancer therapy suffers from a lack of effective chemotherapy. TP53 is second only to KRAS as the most commonly mutated gene in pancreatic cancer with point mutations occurring in 75% of patients. We identified ZMC1 as an allele specific mutant p53 reactivator and lead compound for mutant p53 targeted drug development. ZMC1 restores wildtype structure and function by functioning as a zinc metallochaperone to restore zinc binding to mutant p53 proteins with impaired zinc binding. Our aim was to translate this novel mechanism in vivo using murine pancreatic cancer models. We investigated the pharmacokinetics (PK) and pharmacodynamics (PD) of ZMC1 and performed efficacy studies for allele specificity in nude mice with subcutaneous tumors from murine pancreatic cancer cell lines derived from a genetically engineered mouse model (KPC) expressing mutant KrasG12D and different alleles of TP53 (WT, null, p53R172H, p53R270H). Tumor growth inhibition became apparent only in KPCp53-R172H xenografts but not in KPCp53-R270H. We then performed efficacy studies in the autochthonous KPC model and found that, ZMC1 extended the median survival from 15 to 26 days in the KPCp53-R172H mice (p = 0.05) but not in the KPCp53-R270H mice. We sought to improve the efficacy of ZMC1 by synthesizing it complexed with zinc (Zn-1) in a 2:1 molar ratio. Zn-1 significanlty increased the median survival of KPCp53-R172H mice from 15 to 35 days (p = 0.0042). The apoptosis rate in the tumors (by Immunohistochemistry staining with Cleaved Caspase 3) was also increased by treatment of ZMC1 and Zn-1. These studies indicate that ZMC1 can function in vivo as a mutant p53 targeted anti-cancer drug at doses that are well tolerated. Furthermore, ZMC1 can be optimized by synthesizing it complexed with zinc. Citation Format: Xin Yu, Ashley T. Tsang, Tracy Withers, John Gelleran, David Augeri, S. David Kimball, Darren R. Carpizo. Translating a mutant p53 reactivating drug (ZMC1) in murine pancreatic cancer models. [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 2097.
Evaluation of pretherapeutic Ki67 as predictive marker for response to neoadjuvant chemotherapy in patients with primary breast cancer.
Authors: Alex Farr, Myriam Weber, Georg Pfeiler, Elisabeth Oppolzer, Mohammed Salama, Zsuzsanna Bago-Horvath, Michael Seifert, Christian F. Singer
Journal: Journal of Clinical Oncology (2016)

e12500 Background: The proliferation marker Ki67 is an established prognostic and predictive marker in breast cancer. The association between Ki67 and treatment response in the neoadjuvant setting, however, is still unclear. We have therefore evaluated whether Ki67 can predict pathological complete response (pCR) in women with neoadjuvant chemotherapy (NAC). Methods: We included prospectively collected data of women with primary breast cancer who underwent NAC from 2005–2015 at the Medical University of Vienna, Department of Gynecology. Chemotherapy consisted of 4 cycles epirubicin (90 mg/m2, q3w), followed by 4 cycles docetaxel (100 mg/m2, q3w), which was co-administered with trastuzumab in HER2-positive tumors. Ki67, hormone receptor and HER2-status were examined by immunohistochemistry using core needle biopsy specimens obtained prior to NAC. NAC-related effects were evaluated in surgical specimen; pCR was defined as the absence of invasive cancer in breast and axillary nodes. Results: A total of 95 women with a mean age of 52.9±11.4 years at diagnosis were identified. At biopsy, invasive ductal carcinoma was the predominant histology (n = 76; 80%), with accompanying ductal carcinoma in situ in 17 patients (17.9%). Mean Ki67 at biopsy was 47.4±22.9% and 29.5±25.5% after NAC (p= 0.002); mean difference of Ki67 before and after NAC was -24.9±33.5%. After breast-conserving surgery (n = 62; 65.3%) or mastectomy (n = 29; 30.5%), pCR was observed in 19 (20%) patients. The pCR rate was significantly higher in younger women (OR 1.04 [95%CI, 1.00–1.08]; p= 0.04), those with hormone-receptor-negative (OR 0.77 [95%CI, 0.63–0.94]; p= 0.009), HER2-positive disease (OR 0.69 [95%CI, 0.55–0.87]; p= 0.002) and high Ki67 (14% cut-off) (OR 0.95 [95%CI, 0.93–0.98]; p= 0.002). In a multiple model including all known potential confounders, Ki67 remained the only significant predictor for pCR after NAC (p= 0.007). No significant effect was observed with regard to overall, disease-free and progression-free survival. Conclusions: Our study suggests that in women treated with anthracycline-taxane-based NAC, high pretherapeutic Ki67 is the strongest independent predictive marker for pCR.
Safety and efficacy of single-agent rovalpituzumab tesirine (SC16LD6.5), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate (ADC) in recurrent or refractory small cell lung cancer (SCLC).
Authors: Charles M. Rudin, Maria Catherine Pietanza, Todd Michael Bauer, David R. Spigel, Neal Ready, Daniel Morgensztern, Bonnie S. Glisson, Lauren Averett Byers, Melissa Lynne Johnson, Howard A. Burris, Francisco Robert, Donald K Strickland, Hany Zayed, Ramaswamy Govindan, Scott Dylla, Stanford L. Peng
Journal: Journal of Clinical Oncology (2016)

LBA8505 Background: SCLC remains among the most deadly of malignancies. Rovalpituzumab tesirine is a first-in-class ADC comprised of a humanized monoclonal antibody against DLL3, a dipeptide linker, and a pyrrolobenzodiazepine (PBD) dimer toxin. DLL3 is highly expressed in neuroendocrine tumors, including approximately 80% of SCLC. The emerging results of the SCLC patients (pts) in a first-in-human study (NCT01901653) are reported here. Methods: Pts with progressive SCLC after at least 1 previous systemic therapy were eligible. Efficacy was assessed by the investigator via RECIST v1.1, and toxicity graded per CTCAE v4.03. When available, archived tumor tissue was assessed retrospectively for DLL3 expression by immunohistochemistry. Results: Seventy-four (74) pts were enrolled at dose levels ranging from 0.05 to 0.8 mg/kg at either q3w or q6w. Among evaluable pts treated at doses of 0.2-0.4 mg/kg, 15/61 (25%; 95% CI 15-37%) achieved a best response of PR or CR, and 44/61 (72%; 95% CI 59-83%) achieved clinical benefit (best response of at least SD). Among pts with available archive tissue specimens and ≥ 50% of cells expressing DLL3 (DLL3 hi , an intended companion diagnostic cutoff), 12/22 (55%; 95% CI 32-76%) achieved a best response of PR or CR, and 20/22 (91%; 95% CI 71-99%) achieved clinical benefit, with a median overall survival of 8 (range 1-18+) months. In 3 rd line DLL3 hi pts (n = 10), where no approved therapy currently exists, the ORR and CBR were 70% and 90%, respectively, with at least 4 evaluable pts achieving OS of &gt; 6 (8, 15, 18 and 18) months. Among responders treated at the phase 2 dose of 0.3 mg/kg, the median duration of response was 6 (range 1-8+) months. Among all SCLC pts, the most common grade 3+ toxicities considered study drug-related have included serosal effusions (14%), thrombocytopenia (12%) and skin reactions (8%). Conclusions: With manageable toxicity, rovalpituzumab tesirine demonstrates encouraging single-agent anti-tumor activity and durability in recurrent or refractory SCLC. A single-arm pivotal study in 3 rd line DLL3-expressing SCLC has been initiated. Clinical trial information: NCT01901653.