tbuckley/cabot-search huggingface dataset:
Abstract 3054: Bioenergetic signature of stromal cells defines the aggressiveness of prostate cancer
Authors: Praveen Kumar Vayalil, Aimee Landar
Journal: Cancer Research (2015)

Abstract Cancer-associated fibroblasts, though derived from multiple lineages, share common as well as unique characteristics and play a critical role in various aspects of neoplasia. Their activities range from contributing to tumor formation to promoting the growth and invasion of tumors. They also promote angiogenesis, provide a metabolically friendly tumor environment, and confer resistance to chemotherapy and radiation. Clinical trials targeting stromal cells were disappointing. The reason underlying this failure has been ascribed to the fact that stromal cells do change during cancer progression to aggressive form. As the cancer progresses, both prostate cancer cells as well as stromal cells have to ‘functionally adapt’ to the microenvironment within the tumor mass and mutually support their growth in a hostile environment. The major environmental factor that molds the biology of cancer cells and stromal components is low oxygen tension within the tumor. The key cellular organelle that is functionally affected by exposure to different oxygen tensions is the mitochondria. In this study we present the data on the progressive changes in the stromal cell mitochondrial function in relation to the aggressiveness of prostate cancer at atmospheric oxygen and at different oxygen tensions. This study reveals the potential use of mitochondrial functional assay for the screening of compounds that specifically target the bioenergetics of stromal cells. This information may also unravel the metabolic interaction between tumor- microenvironment that contributes to tumor development and progression of prostate cancer and potential mechanism of resistance to therapy offered by stromal cells. Citation Format: Praveen Kumar Vayalil, Aimee Landar. Bioenergetic signature of stromal cells defines the aggressiveness of prostate 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 3054. doi:10.1158/1538-7445.AM2015-3054
Anti-cachectic effects of a novel peptide nucleic acid: Preliminary results of a phase 1/11 clinical trial
Authors: J. T. D'Olimpio, S. Z. Hirschman, Z. Shtemer, M. Didiego
Journal: Journal of Clinical Oncology (2004)

8087 Background: Wasting syndromes in Cancer and AIDS have similar patho-physiologic mechanisms and treatment remains problematic, especially in advanced disease. A novel Peptide Nucleic Acid (AVR 118), has been shown to improve weight gain and quality of life in multiple anecdotal reports. It was approved for clinical trial by the Israeli Health Ministry in June 2002. Methods: In a Phase 1/2 open label dose escalation format, IRB approval was obtained in the 2 participating Institutions and informed consent was obtained for each patient.10 cachectic patients with advanced AIDS and 2 cachectic patients with advanced pancreatic cancer resistant to chemotherapy were administered AVR 118 subcutaneously at a dose of 0.4 ml per day for 28 days.5 additional AIDS patients continued on 2 ml subcutaneously per day for 28 days. Each patient was followed for 28 days after the treatment period was completed. Weight, percent fat and strength were measured using standardized methods. Any adverse events were monitored per protocol, and each chart was extracted for quality of life parameters including appetite and energy/fatigue level. Results: AIDS: At the 0.4ml dose, 70% of patients had slight weight gain or stabilization of weight, all patients had increases in appetite by week 4,60% reported increase in energy and ADL's, mean strength increase was 8%, 70% showed increase body fat ( mean 15%).At the 2ml dose all patients improved appetite by week 2, with mean fat increase of 25% and strength increase of 32%, all had improved energy and ADL's by week 3.Pancreatic Cancer 0.4 ml dose: Both patients had improved weight (4% increase) percent fat (20% increase) and strength (5% increase) during the 28 day treatment period .When the drug was withdrawn, the effect was lost in most patients. No adverse events were noted in either group. An additional 15 AIDS patients and 13 solid tumor patients are planned for accrual. Conclusions: Peptide Nucleic Acid complex (AVR 118) appears to be a nontoxic novel drug to treat cachexia in AIDS and cancer patients and merits further study. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Advanced Viral Research Advanced Viral Research Advanced Viral Research
Phase I Evaluation of Immune Therapy with Ex-Vivo Expanded and Activated Gamma Delta T Cells.
Authors: Qiao Wang, Jacqueline S. Morley, Hang-Fai So, Stephen R. Mattarollo, Tomomi Hagi, Hirotake Tokuyama, Vy Truong, Mie Nieda, Kiyoshi Yokokawa, Andrew Nicol
Journal: Blood (2006)
Abstract 1762: Verbascoside promotes apoptosis by regulating HIPK2-p53 signaling in human colorectal cancer
Authors: Lihong Zhou, Yuanyuan Feng, Yongjie Jin, Xuan Liu, Hua Sui, Ni Chai, Xingzhu Chen, Ningning Liu, Yan Wang, Qi Li
Journal: Cancer Research (2015)

Abstract Background: We investigated the role of the HIPK2-p53 signaling pathway in tumorigenesis and resistance to the drug Verbascoside (VB) in colorectal cancer (CRC), using in vivo and in vitro experiments. Methods: Primary human CRC samples and normal intestinal tissues from patients were analyzed for HIPK2 expression by immunohistochemistry (IHC) and its expression was correlated against patients’ clinicopathological characteristics. Human CRC HCT-116 cells were implanted in BALB/c nude mice; mice with xenografted tumors were randomly administrated vehicle (control), 20, 40, or 80 mg/mL VB, or 1 mg/mL fluorouracil (5-FU). HIPK2, p53, Bax, and Bcl-2 expression in these tumors were determined by IHC. In vitro effects of VB on CRC cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry; HIPK2, p53, p-p53, Bax, and Bcl-2 were measured by western blot. Results: IHC analysis for 100 human CRC tumor samples and 20 normal intestinal tissues, showed HIPK2 expression to inversely correlate with Dukes stage and depth of invasion in CRC (P &amp;lt;0.05). In vivo, the inhibition rates of 20, 40, and 80 mg/mL VB on CRC xenograft tumor weight were 42.79%, 53.90%, and 60.99%, respectively, and were accompanied by increased expression of HIPK2, p53, and Bax, and decreased Bcl-2 expression in treated tumors. In vitro, VB significantly inhibited proliferation of CRC cell lines HCT-116, HT-29, LoVo, and SW620, in a time- and dose-dependent manner. The apoptosis rates of 25, 50, and 100 μM VB on HCT-116 cells were 10.83 ± 1.28, 11.25 ± 1.54, and 20.19 ± 2.87%, and on HT-29 cells were 18.92 ± 6.12, 21.57 ± 4.05, and 25.14 ± 6.73%, respectively. In summary, VB treatment significantly enhanced the protein expression of pro-apoptotic HIPK2, p53, p-p53, Bax, and decreased anti-apoptotic Bcl-2 expression in CRC cells. Conclusions: HIPK2 protein modulates the phosphorylation status of p53, and levels of Bax and Bcl-2 in CRC. We also found that VB effectively activated the HIPK2-p53 signaling pathway, resulting in increased CRC cells apoptosis. Note: This abstract was not presented at the meeting. Citation Format: Lihong Zhou, Yuanyuan Feng, Yongjie Jin, Xuan Liu, Hua Sui, Ni Chai, Xingzhu Chen, Ningning Liu, Yan Wang, Qi Li. Verbascoside promotes apoptosis by regulating HIPK2-p53 signaling in human 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 1762. doi:10.1158/1538-7445.AM2015-1762
Outcome of Pediatric Patients with Acute Myeloid Leukemia and -5/5q-Abnormalities Enrolled On Five Children's Oncology Group Acute Myeloid Leukemia Treatment Protocols
Authors: Donna L Johnston, Todd A. Alonzo, Robert B. Gerbing, Betsy A. Hirsch, Nyla A. Heerema, Yaddanapudi Ravindranath, William G. Woods, Beverly J. Lange, Alan S. Gamis, Susana C. Raimondi
Journal: Blood (2012)
Serum Soluble Syndecan-1 Levels at Diagnosis Constitute an Independent Prognostic Factor of Survival in Myeloma That May Further Differentiate Patients within the ISS Stages.
Authors: Marie-Christine Kyrtsonis, Theodoros P. Vassilakopoulos, Argyro Papadogiannis, Tatiana Tzenou, Christina Kalpadakis, Antoine Antoniadis, Maria N. Dimopoulou, Marina P. Siakantaris, Stella I. Kokoris, Evangelia M. Dimitriadou, Maria K. Angelopoulou, Ellen Plata, Panagiotis Tsaftaridis, Gerassimos A. Pangalis
Journal: Blood (2005)
P80 Symptoms, delay to presentation and survival in lung cancer
Authors: WY Chan, A Clark, U Dernedde, T Roques, M Burton, J Kotecha, A Wilson, C Martin
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> We aimed to study quantitatively the lung cancer pathway from first symptom to treatment and to explore relationship between symptoms, delay and survival. <h3>Methods</h3> Newly diagnosed lung cancer patients, referred to Oncology clinics in Norfolk 2008–2012, completed systematic questionnaires regarding date of onset of each symptom, MRC dyspnoea score and% weight loss. GPs also completed questionnaires. Additional patient, pathway and tumour data were retrieved from hospital records. The cancer pathway was recorded in five phases: 1) first symptom to GP presentation, 2) to secondary care (SC) referral, 3) to SC appointment, 4) to MDT meeting or date of diagnosis and 5) to treatment commencing. <h3>Results</h3> Of 379 patients, mean age was 70.1 years, staging was: I-II (13.7%), III (34.3%) and IV (52%). Cohort survival was 6.1% with minimum follow-up of 39 months. Mean phase lengths were 221.8, 45.8, 10.7, 21.3, 34.7 days for phases 1–5 respectively. Phase 1 was significantly longer (p &lt; 0.01). Mean phase 1 was shorter in stage III-IV than I-II, 200 and 245 days respectively (p &lt; 0.05), in ex-/never-smokers (191.6 days) than smokers (264.2 days) (p = 0.022) and if first symptom was haemoptysis compared to cough or dyspnoea. 36.9% patients felt they delayed seeing their GP. Commonest reasons were: thinking symptoms were insignificant (35%), anxiety (28.6%) and denial (20%). Good correlation was seen between patient and GP reported dates. Reported symptoms included (% initial symptoms in parenthesis): cough 71% (62.8%), dyspnoea 62.8% (27.2%, chest pain 37.7% (8.7%), haemoptysis 28% (4.2%). Symptoms conferring increased hazard of death were defined as B symptoms. These were: grade 4/5 dyspnoea, hoarseness or loss of voice, metastatic pain and systemic symptoms (HRs 1.77, 1.53, 2.21, 1.93 respectively, p &lt; 0.001). Patients with initial cough/mild dyspnoea have means of 127/210 days before B symptoms develop. Overall no relation was found between phase lengths 1–4 and survival. Survival increased if phase 5 was &gt;31 compared to ≤31 days (HR 0.74, p = 0.006). <h3>Conclusions</h3> Phase 1 is longest. There is no relation between phase length and survival except in phase 5. Symptoms are more important to survival than delay. Effective therapy started within 3 months (before B symptoms) could increase survival.
PWE-348 Is it reasonable to investigate all patients presenting with rectal bleeding with flexible sigmoidoscopy alone?: Abstract PWE-348 Table 1
Authors: CK Tai, A Jewison, B Beauerle, F Chedgy, G Sadler
Journal: Gut (2015)

<h3>Introduction</h3> NICE guidelines recommend that patients with rectal bleeding at risk of cancer should be referred for further investigation.<sup>1</sup>The choice of investigation is at the discretion of the clinician. A retrospective study of patients who underwent curative resection of proximal colorectal malignancy reported a 3% chance of missing right-sided cancers if flexible sigmoidoscopy alone is performed.<sup>2</sup>The aim of our study was to evaluate the incidence of right-sided malignancy in patients undergoing colonoscopy for rectal bleeding, to stratify this risk by age, and to compare these rates in 2 different patient populations. <h3>Method</h3> The endoscopy databases at St George’s Hospital, London (SGH) and Royal Surrey County Hospital (RSCH) were interrogated to identify all colonoscopies performed for rectal bleeding. Data were available over 32 (SGH) and 26 (RSCH) years. Results were stratified according to age and location of pathology, and differences between the 2 populations were analysed using Z-test. <h3>Results</h3> A total of 10482 colonoscopies were performed for rectal bleeding. 849 (8.1%) identified lesions suspicious for cancer. Of all suspected cancers, 94 (11.2%) were right-sided. The overall incidence of right-sided cancer was 0.9%. Overall incidence of right-sided cancer found at endoscopy in patients investigated for rectal bleeding in both units and stratified by age: Sub-analysis of the SGH data revealed that 54.1% of patients with right-sided lesions would have been found to have an indication to undertake completion colonoscopy had a flexible sigmoidoscopy been undertaken in the first instance. <h3>Conclusion</h3> These data provide an estimate of the age-specific risk of right-sided CRC in patients presenting with rectal bleeding. No significant difference regarding cancer incidence between our 2 diverse patient populations could be demonstrated, suggesting that these results might be generalisable to a wider population. The overall yield of right-sided cancer across age ranges remains low. We propose that flexible sigmoidoscopy might reasonably be offered to all patients presenting with rectal bleeding, regardless of age, as a first line investigation. Adopting such a strategy will likely result in cost-savings and have beneficial waiting list implications, without engendering risk of missing significant pathology. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> BSG Clinical Commisioning Report for Rectal Bleeding [last accessed 11/2/15] Badiani S, Desai A and Chapman MAS. Is whole colonic imaging necessary for symptoms of change in bowel habit and/or rectal bleeding? Colorectal disease. 2012;14:1197–1200
Impact of SERPINC1, PROC and PROS1 Mutations on the Thrombotic Phenotype in Children with Venous Thromboembolism: An Observational Multicenter Cohort Study
Authors: Verena Limperger, Gili Kenet, Christine Heller, Karin Kurnik, Ralf Knoefler, Rolf M Mesters, Susan Halimeh, Ulrike Nowak-Göttl
Journal: Blood (2014)
The ASCO Breast Cancer Registry pilot: Implementation of a multisite community practice registry and treatment plan/summary program.
Authors: A. H. Partridge, V. W. Norris, V. S. Blinder, B. A. Cutter, M. T. Halpern, J. Malin, M. N. Neuss, A. C. Wolff
Journal: Journal of Clinical Oncology (2011)

6101 Background: Current approaches to quality assessment require retrospective data collection that limits opportunities for quality improvement. The goal of the ASCO Breast Cancer Registry (BCR) Pilot was to evaluate the feasibility and acceptability of prospective data collection to support quality assessment in community oncology practices. In addition, data were used in real time to create treatment plans and summaries to be shared with patients. Methods: Twenty diverse outpatient oncology practices were selected to participate and entered clinical data into the BCR through a web-based tool on each new patient with stage 0-3 breast cancer between 9/09 and 11/10. Using the tool, individual treatment plans and summaries were then created and shared with patients. Practices received practice-specific and aggregate BCR data on 9 quality measures. Practices were surveyed twice, soon after starting the pilot and at the end. Practices received a stipend to offset participation costs. Results: Practices entered 2,014 patients in the BCR (range across practices = 9-276). Detailed information on patient demographic/clinical characteristics and treatment was collected. 52% of practice participants replied to the end-of-pilot survey (52 physicians, 49 staff): 73% were satisfied with the overall BCR and its web-based application; 90% of those who had been involved with creating or communicating the treatment plans/summaries found them useful to improve communication between the medical oncologist and the patient; and 93% had a favorable view of using BCR data for practice quality improvement. 31% expressed concern regarding the time required to accomplish at least one aspect of the pilot and 52% indicated the practice incurred additional costs to meet the requirements of the BCR. Conclusions: Prospective data collection for quality assessment is feasible and enables creation of treatment plans/summaries to enhance communication with patients at the point of care. However, practice burden may limit uptake. Future efforts should focus on broadening practice participation and assessing the cost and impact on patient outcomes. This research was funded by Susan G. Komen for the Cure.
Abstract 4586: Association of FUT2 gene variant, gut bacteria and colorectal adenomas
Authors: Winifred Okunola, Amber McCoy, Santosh Dulal, Temitope O. Keku
Journal: Cancer Research (2015)

Abstract The fucosyltransferase 2 (FUT2) gene is responsible for the expression of the ABO blood group antigens. These antigens serve as anchors for a variety of microbes in the gut and may confer increased susceptibility to microbial infections and diseases. We assessed the association between a genetic variant in the FUT2 gene (rs516246) and mucosal-adherent gut bacteria in relation to colorectal adenomas. Genomic DNA from 200 consented screening colonoscopy subjects was genotyped for FUT2 rs516246 using a TaqMan genotyping assay. qPCR was performed to target the 16S rRNA gene for specific bacteria. Statistical analysis included t-test, logistic regression Chi-squared tests and Spearman's correlation test. Results show that, except for age and waist-hip ratio, patient characteristics were similar for cases and controls. Higher abundance of E. coli and Eubacteria was associated with adenoma status. There was a null association between FUT2 genotype and adenomas. Similarly, gut bacteria and adenoma status was not strongly influenced by FUT2 genotype. In conclusion: the FUT2 (rs516246) gene variant does not appear to influence the relationship between gut bacteria and colorectal adenomas. Citation Format: Winifred Okunola, Amber McCoy, Santosh Dulal, Temitope O. Keku. Association of FUT2 gene variant, gut bacteria and colorectal adenomas. [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 4586. doi:10.1158/1538-7445.AM2015-4586
Abstract 2404: Quality assessment of circulating cell-free DNA using multiplexed droplet-digital PCR
Authors: Tania Contente-Cuomo, Muhammed Murtaza
Journal: Cancer Research (2015)

Abstract Recent proof-of-principle studies have demonstrated potential utility of sequencing cell-free DNA in cancer diagnostics. However, little is understood about the effect of fragment size distributions in plasma DNA on the performance of sequencing-based assays. We developed a multiplexed assay to perform one-step analysis of DNA quantity and integrity from minute amounts of cell-free DNA using picoliter droplet digital PCR. Primers were designed to amplify 5 short PCR products (67-71 bp) and 4 long PCR products (439-522 bp) from independent quiescent regions of the human genome. Oligonucleotide probes targeting each of the short and long products were labeled with fluorescent dyes FAM and TET respectively. We evaluated the performance of our assay using control human genomic DNA sheared using sonication to an average of 150 bp, 300 bp, 500 bp and 1000 bp fragment sizes. We observed that relative quantities of short and long PCR products reflect integrity of sheared input DNA. We further observed that accurate quantification and assessment of integrity could be achieved using picogram amounts of cell-free DNA (as few as 200 pg in current assessments). Finally, our results were predictive of diversity and obtainable depth-of-coverage in next-generation sequencing libraries made from cell-free DNA samples. Citation Format: Tania Contente-Cuomo, Muhammed Murtaza. Quality assessment of circulating cell-free DNA using multiplexed droplet-digital PCR. [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 2404. doi:10.1158/1538-7445.AM2015-2404
Imatinib Frontline Therapy Is Safe and Effective in Patients with Chronic Myeloid Leukemia (CML) with Liver and/or Renal Dysfunction.
Authors: Weigang Tong, Hagop Kantarjian, Susan O’Brien, Stefan Faderl, Farhad Ravandi, William G Wierda, Steven Kornblau, Gautam Borthakur, Guillermo Garcia-Manero, Elizabeth Burton, Mary Beth Rios, Jorge Cortes
Journal: Blood (2008)
Truncating de novo mutations in the Krüppel-type zinc-finger gene ZNF148 in patients with corpus callosum defects, developmental delay, short stature, and dysmorphisms
Authors: Servi J. C. Stevens, Anthonie J. van Essen, Conny M. A. van Ravenswaaij, Abdallah F. Elias, Jaclyn A. Haven, Stefan H. Lelieveld, Rolph Pfundt, Willy M. Nillesen, Helger G. Yntema, Kees van Roozendaal, Alexander P. Stegmann, Christian Gilissen, Han G. Brunner
Journal: Genome Medicine (2016)

Krüppel-type zinc finger genes (ZNF) constitute a large yet relatively poorly characterized gene family. ZNF genes encode proteins that recognize specific DNA motifs in gene promotors. They act as transcriptional co-activators or -repressors via interaction with chromatin remodeling proteins and other transcription factors. Only few ZNF genes are currently linked to human disorders and identification of ZNF gene-associated human diseases may help understand their function. Here we provide genetic, statistical, and clinical evidence to support association of ZNF148 with a new intellectual disability (ID) syndrome disorder. Routine diagnostic exome sequencing data were obtained from 2172 patients with ID and/or multiple congenital anomalies. In a cohort of 2172 patient–parent trios referred for routine diagnostic whole exome sequencing for ID and/or multiple congenital anomalies (MCA) in the period 2012–2016, four patients were identified who carried de novo heterozygous nonsense or frameshift mutations in the ZNF148 gene. This was the only ZNF gene with recurrent truncating de novo mutations in this cohort. All mutations resulted in premature termination codons in the last exon of ZNF148. The number of the de novo truncating mutations in the ZNF148 gene was significantly enriched (p = 5.42 × 10−3). The newly described ZNF148-associated syndrome is characterized by underdevelopment of the corpus callosum, mild to moderate developmental delay and ID, variable microcephaly or mild macrocephaly, short stature, feeding problems, facial dysmorphisms, and cardiac and renal malformations. We propose ZNF148 as a gene involved in a newly described ID syndrome with a recurrent phenotype and postulate that the ZNF148 is a hitherto unrecognized but crucial transcription factor in the development of the corpus callosum. Our study illustrates the advantage of whole exome sequencing in a large cohort using a parent–offspring trio approach for identifying novel genes involved in rare human diseases.
Analysis of 3 Year Post Marketing Surveillance of Eculizumab in Japan
Authors: Naoshi Obara, Haruhiko Ninomiya, Shigeru Chiba, Kensuke Usuki, Kaichi Nishiwaki, Itaru Matsumura, Tsutomu Shichishima, Shinichiro Okamoto, Jun-ichi Nishimura, Kazuma Ohyashiki, Shinji Nakao, Kiyoshi Ando, Tatsuya Kawaguchi, Hideki Nakakuma, Yoko Hamada, Akihiko Shimono, Taroh Kinoshita, Keiya Ozawa, Mitsuhiro Omine, Yuzuru Kanakura
Journal: Blood (2014)