tbuckley/cabot-search huggingface dataset:
Abstract 1096: microRNA-193a-3p acts as a tumor suppressor in BRAF-mutated colorectal cancer
Authors: Hidekazu Takahashi, Masanobu Takahashi, Shin Takahashi, Hideki Shimodaira, Chikashi Ishioka
Journal: Cancer Research (2016)

Abstract The aim of this study was to identify microRNAs (miRNAs) specifically dysregulated in BRAF-mutant colorectal cancer, a malignant subtype of colorectal cancer. The genome-wide miRNA expression analysis in a screening set (n = 30) identified 22 miRNAs specifically dysregulated in BRAF-mutant cancers. Among the top 5 dysregulated miRNAs, the validation analysis using another set of patients (n = 34) confirmed miR-31 and miR-135b as significantly up-regulated miRNAs and miR-193a-3p as a significantly down-regulated one. Moreover, functional assays supported its tumor-suppressive role in colorectal cancer. Finally, the expression status of miR-193a-3p correlated with clinical outcome of patients treated with anti-EGFR antibodies. Taken together, these results show a novel functional role of miR-193a-3p as a tumor suppressive miRNA in colorectal cancer, particularly with BRAF mutations. Further studies are needed to clarify the precise molecular mechanisms as to how this miRNA is involved in colorectal tumorigenesis, which could help further develop a therapeutic strategy for colorectal cancer. Citation Format: Hidekazu Takahashi, Masanobu Takahashi, Shin Takahashi, Hideki Shimodaira, Chikashi Ishioka. microRNA-193a-3p acts as a tumor suppressor in BRAF-mutated colorectal cancer. [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 1096.
Abstract 3267: Eltd1 as an anti-angiogenic therapy against glioma tumors
Authors: Jadith Ziegler, Nataliya Smith, Debra Saunders, Blake Evans, James D. Battiste, Michael Sughrue, Paul Tompkins, Jake Sutton, Megan Lerner, Patricia Coutinho de Souza, Kar-Ming Fung, Jonathan Wren, Rheal Towner
Journal: Cancer Research (2016)

Abstract Gliomas consist of up to 80% of malignant brain tumors that are invasive and typically resistant to radiotherapy and chemotherapy. Finding biomarkers to high-grade gliomas can enable better diagnosis and therapeutic intervention for this disease. We have identified ELTD1 as a biomarker for high-grade human gliomas. Here, we report our findings in vivo using anti-ELTD1 (at two different concentrations), Bevacizumab, and IgG antibodies on human G55 xenograft glioma models. Using MRI, we investigate tumor growth, perfusion, tumor blood flow, and microvessel density changes in mice. In addition, survival rates were measured. Mice were implanted with human G55 xenograft glioma cells and were left untreated, administered anti-ELTD1, (1 mg/kg or 2 mg/kg every 2-3 days) Bevacizumab (2 mg/kg every 2-3 days) or IgG (1 mg/kg every 2-3 days). MRI experiments were performed to assess tumor growth and calculate tumor volumes. In order to assess angiogenesis, representative histology slides were obtained and stained for blood vessels using CD34 antibody and microvessel density (MVD) was then calculated. Finally, cerebral blood flow rates from MR perfusion imaging was obtained as well as MR angiography to determine tumor blood volume from mice in each group. Our results show a significant decrease in tumor volumes and increase in percent survival for mice treated with 1 mg/kg and 2 mg/kg of ELTD1 antibody compared to untreated mice and IgG treated mice. Mice also had an increase in perfusion, decrease in tumor blood volume and decrease in MVD. Anti-ELTD1 antibody therapy reduced tumor volumes, prolonged life, and overall decreased angiogenesis in our mouse model. Anti-ELTD1 therapy may be an ideal anti-angiogenic treatment for high-grade gliomas. Citation Format: Jadith Ziegler, Nataliya Smith, Debra Saunders, Blake Evans, James D. Battiste, Michael Sughrue, Paul Tompkins, Jake Sutton, Megan Lerner, Patricia Coutinho de Souza, Kar-Ming Fung, Jonathan Wren, Rheal Towner. Eltd1 as an anti-angiogenic therapy against glioma tumors. [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 3267.
Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia
Authors: S Eldfors, H Kuusanmäki, M Kontro, M M Majumder, A Parsons, H Edgren, T Pemovska, O Kallioniemi, K Wennerberg, N Gökbuget, T Burmeister, K Porkka, C A Heckman
Journal: Leukemia (2016)

TCF3-PBX1 (E2A-PBX1) is a recurrent gene fusion in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), which is caused by the translocation t(1;19)(q23;p13). TCF3-PBX1 BCP-ALL patients typically benefit from chemotherapy; however, many relapse and subsequently develop resistant disease with few effective treatment options. Mechanisms driving disease progression and therapy resistance have not been studied in TCF3-PBX1 BCP-ALL. Here, we aimed to identify novel treatment options for TCF3-PBX1 BCP-ALL by profiling leukemia cells from a relapsed patient, and determine molecular mechanisms underlying disease pathogenesis and progression. By drug-sensitivity testing of leukemic blasts from the index patient, control samples and TCF3-PBX1 positive and negative BCP-ALL cell lines, we identified the phosphatidylinositide 3-kinase delta (p110δ) inhibitor idelalisib as an effective treatment for TCF3-PBX1 BCP-ALL. This was further supported by evidence showing TCF3-PBX1 directly regulates expression of PIK3CD, the gene encoding p110δ. Other somatic mutations to TP53 and MTOR, as well as aberrant expression of CXCR4, may influence additional drug sensitivities specific to the index patient and accompanied progression of the disease. Our results suggest that idelalisib is a promising treatment option for patients with TCF3-PBX1 BCP-ALL, whereas other drugs could be useful depending on the genetic context of individual patients.
James Riddick Heron
Authors: Richard J L Heron
Journal: BMJ (2016)

James Riddick Heron (“Jim”) was born in Lanarkshire, Scotland, and moved to Birmingham as a child. He attended King Edward’s School and studied medicine at Birmingham University Medical School. Thereafter, he trained in neurology at the Royal Free Hospital in London, the National Hospital for Neurology and Neurosurgery in London’s Queen Square, and the Queen Elizabeth Hospital in Birmingham.

While at the Royal Free Hospital, …
Immunophenotypical Minimal Residual Disease as a Short Term Endpoint for Monitoring Effects of Targeted Inhibitors in Acute Myeloid Leukemia.
Authors: Corine J. Hess, Nicole Feller, Fedor Denkers, Pauline A. Merle, Gert J. Ossenkoppele, Quinten Waisfisz, Gerrit Jan Schuurhuis
Journal: Blood (2005)
Abstract 6: Metabolomics of Gleason score in prostate tumor tissue and serum
Authors: Kathryn Penney, Svitlana Tyekucheva, Massimo Loda
Journal: Cancer Research (2016)

Abstract Background: Gleason score is currently the best clinical predictor of prostate cancer specific-mortality. Identifying biomarkers associated with Gleason score can improve prediction and advance the understanding of the biology of aggressive disease. Using gene expression data, we previously determined that metabolism pathways, including pyrimidine, propanoate, and beta-alanine, were differentially expressed in high and low grade tumors. The goal of this study is to identify metabolites that differ in low and high Gleason score tumors and in blood from these patients. Methods: Metabolic profiling was performed on Gleason score 6 (n = 53) and Gleason score ≥8 (n = 32) radical prostatectomy tumor tissue specimens, and on serum samples from the time of diagnosis (n = 30 Gleason score 6 and n = 19 Gleason score ≥8) from the DF/HCC Prostate Cancer SPORE Cohort. Samples were prepared for analysis by Metabolon, Inc. with their standard solvent extraction method to recover small molecules. Metabolites were identified and quantified by gas and liquid chromatography and mass spectrometry. Missing values were calculated using k-nearest neighbor imputation, and sample values were normalized across batches. The metabolite levels were compared across Gleason score 6 and Gleason score ≥8 tumors and serum using a Wilcoxon test. Results: In the tumor tissue, 207 metabolites were identified. Of these, 30 were present in significantly different amounts in high and low Gleason score tumors, including previously reported citrate (p = 0.002) and spermine (p = 0.003). In a pathway analysis, the propanoate pathway was significantly different in high and low Gleason (p = 0.03), but not the pyrimidine or beta-alanine pathways (p&amp;gt;0.05). In serum, 15 individual metabolites had significantly different levels, including uridine (p = 0.008) and N-acetylserine (p = 0.0001). Conclusions: Metabolite levels do differ in high and low Gleason score prostate tumor tissue. The novel serum results suggest that metabolites in blood may serve as biomarkers of tumor differentiation. Our ongoing research will build prediction models, and will determine if the blood metabolites can indicate the presence of high-Gleason score tumor not detected at biopsy and could serve as biomarkers for monitoring disease progression in active surveillance patients. Citation Format: Kathryn Penney, Svitlana Tyekucheva, Massimo Loda. Metabolomics of Gleason score in prostate tumor tissue and serum. [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 6.
Group B Streptococcus Degrades Cyclic-di-AMP to Modulate STING-Dependent Type I Interferon Production
Authors: Warrison A. Andrade, Arnaud Firon, Tobias Schmidt, Veit Hornung, Katherine A. Fitzgerald, Evelyn A. Kurt-Jones, Patrick Trieu-Cuot, Douglas T. Golenbock, Pierre-Alexandre Kaminski
Journal: Cell Host & Microbe (2016)
Abstract 2536: AP-1/Fra-1 as a target for therapy promotes chemoradiosensitivity of cancer and cancer stem cells
Authors: Bhudev C. Das, Abhishek Tyagi, Bal Gangadhar Roy, Alok C. Bharti
Journal: Cancer Research (2016)

Abstract Transcription factor activator protein-1 (AP-1) super-family is known to modulate expression of array of genes during development of many cancers. It is also an indispensable factor for efficient expression of high risk HPV oncogenes E6/E7. Recent studies demonstrated the role of AP-1 in promoting stemness/quiescence of cancer stem cells. We have recently reported that HPVE6 oncogene controls stemness and self-renewal of cervical cancer stem cells through Hes1/NOTCH-1expression but little is known about factor(s) responsible for chemo- radioresistance of cancer stem cells. To understand this we have dissected the role of AP-1and its family members by using a herbal compound, curcumin and UV irradiation in cervical cancer. We isolated cervical cancer stem cells and enriched them by sequential gating from HPV+ve and HPV-ve human cervical cancer cell lines (SiHa and C33a) using a set of functional and phenotypic markers (ABCG2, CD49f, CD71, CD133). The isolated cervical cancer stem cells (SP+ve→CD49+veCD71−ve→CD133+ve) designated as CaCxSLCs displayed spheroid forming and self-renewal property with increased expression of HPVE6, AP-1 transcripts and a higher AP-1 DNA-binding activity compared to non-stem cancer cells (NSP−ve→CD49−veCD71+ve→ CD133−ve) or unsorted parental cells. Treatment with UV-radiation alone resulted in clonogenic survival of CaCxSLCs but not non-stem cancer cells with enhanced AP-1 expression and activation. In contrast, CaCxSLCs treated with UV in combination with curcumin, resulted in complete loss of AP-1 DNA-binding activity followed by decrease in sphere formation and percentage of SP cells but an increased expression of the fos-related antigen-1 (Fra-1) which has been earlier shown to us have tumor suppressor activity in cervical cancer. Our study demonstrates a critical role of AP-1/Fra-1 signaling in imparting radiosensitization of cervical cancer stem cells. Curcumin, which down regulates almost all signalling pathways, including all members of AP-1 except Fra-1 indicating its role in chemo-radiosensitization of cancer stem cells. Thus combining curcumin with conventional cancer drugs may make cancer treatment most effective. Citation Format: Bhudev C. Das, Abhishek Tyagi, Bal Gangadhar Roy, Alok C. Bharti. AP-1/Fra-1 as a target for therapy promotes chemoradiosensitivity of cancer and cancer stem cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2536.
Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1) Expression Is Increased in Ph−Chronic Myeloproliferative Disorders and Correlates with the Microvessel Density and VEGF.
Authors: Giorgio Lambertenghi Deliliers, Umberto Gianelli, Claudia Vener, Nicola S. Fracchiolla, Elisa De Camilli, Leonardo Boiocchi, Rossella Calori, Alessandra Iurlo, Franca Radaelli, Silvano Bosari, Guido Coggi
Journal: Blood (2007)
Screening for Skin Cancer in Adults
Authors: Karen J. Wernli, Nora B. Henrikson, Caitlin C. Morrison, Matthew Nguyen, Gaia Pocobelli, Paula R. Blasi
Journal: JAMA (2016)

<h3>Importance</h3> Skin cancer, primarily melanoma, is a leading cause of morbidity and mortality in the United States. <h3>Objective</h3> To provide an updated systematic review for the US Preventive Services Task Force regarding clinical skin cancer screening among adults. <h3>Data Sources</h3> MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies published from January 1, 1995, through June 1, 2015, with surveillance through February 16, 2016. <h3>Study Selection</h3> English-language studies conducted in asymptomatic populations 15 years and older at general risk for skin cancer. <h3>Data Extraction and Synthesis</h3> Relevant data were abstracted, and study quality was rated. <h3>Main Outcomes and Measures</h3> Melanoma incidence and mortality, harms from cancer screening, diagnostic accuracy, and stage distribution. <h3>Results</h3> No randomized clinical trials were identified. There was limited evidence on the association between skin cancer screening and mortality. A German ecologic study (n = 360 288) found a decrease of 0.8 per 100 000 melanoma deaths in a region with population-based skin cancer screening compared with no change or slight increases in comparison regions. The number of excisions needed to detect 1 skin cancer from clinical visual skin examinations varied by age and sex; for example, 22 for women 65 years or older compared with 41 for women aged 20 to 34 years. In 2 studies of performing visual skin examination, sensitivity to detect melanoma was 40.2% and specificity was 86.1% when conducted by primary care physicians (n = 16 383). Sensitivity was 49.0% and specificity was 97.6% when skin examinations were performed by dermatologists (n = 7436). In a case-control study of melanoma (n = 7586), cases diagnosed with thicker lesions (&gt;0.75 mm) had an odds ratio of 0.86 (95% CI, 0.75-0.98) for receipt of a physician skin examination in the prior 3 years compared with controls. Eight cohort studies (n = 236 485) demonstrated a statistically significant relationship between the degree of disease involvement at diagnosis and melanoma mortality, regardless of the characterization of the stage or lesion thickness. Tumor thickness greater than 4.0 mm was associated with increased melanoma mortality compared with thinner lesions, and late stage at diagnosis was associated with increased all-cause mortality. <h3>Conclusions and Relevance</h3> Only limited evidence was identified for skin cancer screening, particularly regarding potential benefit of skin cancer screening on melanoma mortality. Future research on skin cancer screening should focus on evaluating the effectiveness of targeted screening in those considered to be at higher risk for skin cancer.
Abstract 3068: Anti-tumor effect of DHP107, a mucoadhesive lipid formulae of oral paclitaxel, in bladder cancer model
Authors: Se Hyun Kim, Jung Min Kim, Tae Soo Kim, Won Suk Lee, Woo Sun Kwon, Seung Tak Lim, Joong Bae Ahn, Se-Kyu Kim, Yeong Woo Jo, Sun Young Rha
Journal: Cancer Research (2016)

Abstract Purpose: Paclitaxel is an effective anti-neoplastic agent in many solid tumors including bladder cancer. With the development of new drug delivery strategies, novel formulations of Cremophor EL-free paclitaxel have been developed. Here, we investigated the in vitro and in vivo anti-tumor effect of a mucoadhesive oral formulation of paclitaxel (DHP107) in comparison with iv paclitaxel in a human bladder cancer model. Methods: Four human bladder cancer cell lines (RT4, T24, J82, HT1376) and one murine bladder cancer cell line (MBT-2) were used in this study. In vitro antitumor activity and underlying mechanisms were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cell-cycle analysis and apoptosis assay. In the in vivo study, RT4 cell line was implanted subcutaneously in the flank of nu/nu mice, and treated with iv paclitaxel and 2 doses of DHP107. The effects were assessed by the tumor growth, body weight and Ki-67 staining in tumor tissues. Results: The IC50 values of DHP107 ranged from 4.15 to 34.72 μg/ml with MTT assay. In RT4 cell line, both drugs induced similar G2-M arrest and apoptosis. The xenograft experiments showed that both DHP107 (per os, 50 mg/kg, equivalent of paclitaxel 10 mg/kg) and iv paclitaxel (intraperitoneal, 10 mg/kg) attenuated the growth of RT4 tumors in mice, equivalently. The higher dose (per os, 100 mg/kg) of DHP107 resulted in increased efficacy compared with the lower dose (50 mg/kg) without weight loss in mice. However, significant weight loss was observed in iv paclitaxel (-20% at Day 11) treated group. We observed significantly decreased proliferation with Ki-67 staining in DHP107 (100 mg/kg) treated group than in DHP107 (50 mg/kg) or iv paclitaxel (10 mg/kg) treated groups. Conclusion: Our findings provide the evidence that DHP107 showed comparable antitumor effect with iv paclitaxel and is a promising anti-tumor agent in bladder cancer. Clinical studies in patients with bladder cancer warrant further investigation. Citation Format: Se Hyun Kim, Jung Min Kim, Tae Soo Kim, Won Suk Lee, Woo Sun Kwon, Seung Tak Lim, Joong Bae Ahn, Se-Kyu Kim, Yeong Woo Jo, Sun Young Rha. Anti-tumor effect of DHP107, a mucoadhesive lipid formulae of oral paclitaxel, in bladder cancer model. [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 3068.
Increased Airport Scrutiny by the Transportation Security Administration of a Patient-Passenger Carrying Ammonium Lactate–Containing Moisturizer
Authors: Allison Zarbo, Ouathek Ouerfelli, Mark Klang, Mario E. Lacouture
Journal: JAMA Dermatology (2016)

Clarification of the differences between related chemical agents is key for maximum security efficiency during transportation.We advise physicians to educate their patients and reassure them that their moisturizer is not dangerous.Current procedures direct patients to alert TSA prior to their travel date and obtain approved labeling to minimize discomfort and stress.Alternatively, patients may arrange to have their ammonium lactate prescribed and ordered at a pharmacy in their destination city.
Hepatitis due to Reactivation of Hepatitis B Virus in Endemic Areas Among Patients With Hepatitis C Treated With Direct-acting Antiviral Agents
Authors: Cheng Wang, Dong Ji, Jing Chen, Qing Shao, Bing Li, Jialiang Liu, Vanessa Wu, April Wong, Yudong Wang, Xiaoyong Zhang, Lei Lu, Chris Wong, Stella Tsang, Zheng Zhang, Jian Sun, Jinlin Hou, Guofeng Chen, George Lau
Journal: Clinical Gastroenterology and Hepatology (2016)
Abstract 1034: Leptin induces early onset and aggressiveness of pancreatic cancer
Authors: Adriana Harbuzariu, Antonio Rampoldi, Danielle S. Daley-Brown, Tia L. Harmon, Derrick J. Beech, Gabriela Oprea-Ilies, Ruben R. Gonzalez-Perez
Journal: Cancer Research (2016)

Abstract Background: During the past 30 years, pancreatic cancer (PC) has constantly been the fourth leading cause of cancer death. PC is usually advanced at the time of diagnosis, with an overall five years survival rate of less than 5%. Obesity, characterized by high levels of leptin, is pandemic in United States and a risk factor for PC. Notch abnormal signaling is linked to carcinogenesis, tumor angiogenesis and self renewal capacity of PC stem cells (PCSC). We have previously shown that leptin induces proliferation of PC cell lines, increases Notch expression, PCSC and tumorsphere formation. To test leptin effects in a PC mouse model, a specific and potent signaling inhibitor bound to nanoparticles, IONP-LPrA2 was produced by us. Hypothesis: High levels of leptin induce early onset and multiplicity of PC xenografts, which is abrogated by IONP-LPrA2 treatment. Methods: Human PC cell line MiaPaCa-2 was challenged with leptin or IONP-LPrA2. The expression of pluripotency associated genes (STAT3, Oct4, Sox2 and NANOG) was evaluated. MiaPaCa-2 cells forming tumorspheres were treated with leptin or IONP-LPrA2 and inoculated into CD1 nu/nu mice. Untreated tumorspheres were inoculated as controls. A group of mice were injected twice a week with IONP-LPrA2. Tumor onset and growth were assessed. PC xenografts were analyzed for expression of Ki67 (proliferation marker), leptin targeted molecules (Notch), PCSC markers etc. Results: Leptin induced the expression of PCSC pluripotency markers. Moreover, leptin treatment of tumorspheres induced early tumor onset and multiplicity. Also, leptin increased proliferation, PCSC and oncogenic markers in PC xenografts. IONP-LPrA2 reduced leptin effects. No changes of mice food intake and body weight were observed. Conclusions: This observation might imply that obese patients are at high risk to develop PC. Inhibition of leptin signaling may be used as preventative or therapeutic strategy for PC, especially in obese patients. Acknowledgements: this work was supported by DOD W81XWH-13-1-0382; NIH/SBIR 1R41CA183399-01A1; Pilot Project Award from MSM/Tuskegee University/UAB Cancer Center partnership grant 5U54CA118638; PC SPORE Grant from UAB to RRGP, and facilities and support services at Morehouse School of Medicine (1G12RR026250-03; NIH RR 03034 and 1C06 RR18386). Citation Format: Adriana Harbuzariu, Antonio Rampoldi, Danielle S. Daley-Brown, Tia L. Harmon, Derrick J. Beech, Gabriela Oprea-Ilies, Ruben R. Gonzalez-Perez. Leptin induces early onset and aggressiveness of pancreatic cancer. [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 1034.