tbuckley/cabot-search huggingface dataset:
Abstract 1570: Defective collagen production by mammary epithelia leads to increased breast cancer metastasis: a novel role of vacuolar ATPase
Authors: Gajendra K. Katara, Arpita Kulshrestha, Sahithi Pamarthy, Liqun Mao, Kenneth D. Beaman
Journal: Cancer Research (2016)

Abstract In cancer cells, vacuolar ATPase (V-ATPase), a multi-subunit enzyme, is expressed on the plasma as well as vesicular membranes and critically influences metastatic behavior. Recently, we have shown that by inhibiting a2 isoform of V-ATPase ‘a’ subunit (a2V) in cancer cells, in vivo tumor growth can be delayed through decreasing essential macrophage population in breast cancer. Here, we investigated whether the same tumor growth inhibition can be attain by deleting a2V in host tissue instead of cancer cell. For this purpose, we deleted a2V gene in the mouse mammary gland using MMTV-Cre lox system. Breast tumors were generated by inoculating E0771 mammary carcinoma in mammary fat pad of a2V knockout (KO) mice. We observed faster tumor growth in KO mice compared to wild type (WT). KO mice tumors showed more infiltration and metastasis of cancer cell as evident by the number of lung and liver lesions. KO mice did not display the characteristic solid tumor phenotype of breast cancer. Based on these observations, we evaluated expression and production of collagen protein which is an important component of the extra cellular matrix, in KO breast tissue. Trichrome staining showed less collagen protein in tumorous as well as in non-tumorous breast tissue of KO mice. Total collagen was measured by the hydroxyl proline assay and analysis showed that KO mice have significantly (P&amp;lt;0.05) less amount of hydroxyl proline compared to WT mice. (16.77 ± 3.74 vs 43.67 ± 6.89). To validate our observation, we knock down a2V in HMEpC mammary epithelial cell line to measure the effect on collagen production. After a2V inhibition, the production of collagen in culture media was reduced. The data show that for an efficient tumor growth, a2V is required in both cancer cell and host tissue. Citation Format: Gajendra K. Katara, Arpita Kulshrestha, Sahithi Pamarthy, Liqun Mao, Kenneth D. Beaman. Defective collagen production by mammary epithelia leads to increased breast cancer metastasis: a novel role of vacuolar ATPase. [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 1570.
Abstract 1567: Prostate cancer-derived exosomes alter the metabolic microenvironment of bone marrow pre-metastatic niche through PKM2 to promote bone metastasis
Authors: Jinlu Dai, Yi Lu, Jian Zhang, Evan Keller
Journal: Cancer Research (2016)

Abstract Tumor-derived exosomes are emerging mediators of tumor progression. We explored the role of prostate cancer (PCa)-derived exosomes (Ex) in PCa bone metastasis. Systemic pre-treatment of mice with PCa-Ex increased PCa tumor growth in bone, this was associated with increased early PCa cell seeding into the bone marrow. PCa-Ex had no direct impact on PCa growth or invasive ability in vitro; whereas, conditioned-media (CM) from PCa-Ex-treated stromal cells increased PCa cell growth, invasion and epithelial mesenchymal transition (EMT). PCa-Ex preferentially targeted bone marrow versus lung or liver stroma when injected IV. Proteomic analysis of PCa-Ex-treated cells revealed that PCa-Ex increased pyruvate kinase M2 (PKM2) protein expression in both ST2 stromal cells and primary bone marrow stromal cells, although PKM2 mRNA expression was not altered. PKM2 protein expression correlated with aggressiveness of PCa cell lines and was highest in serum of PCa patients with metastases compared to those with primary tumors. PCa-Ex induced both autophagy and β-hydroxybutarate (BHB) production from stromal cells. Knockdown of PKM2 in PCa cells resulted in production of PCa-Ex with low PKM2. The low PKM2 PCa-Ex had diminished ability to induce PCa cell growth, autophagy and BHB production. IV PCa-Ex and orthotopic tumors increased bone marrow BHB levels. PCa-Ex treatment of stromal cells induced the CM to (1) increase in oxygen consumption rate (OCR) by 80%; (2) extracellular acidification rate (ECAR) by 25%; and (3) increase ATP production in PCa cells. BHB induced OCR, but not ECAR in a dose responsive fashion. BHB administration induced a dose-responsive increase in intratibial tumor growth in mice. Our experiments indicate that primary tumor PCa-Ex can target the bone marrow microenvironment and educate stromal cells to promote PCa progression through increasing PKM2 expression in stromal cells resulting in ketone production that supports metastatic growth. Overall this demonstrates that primary tumor exosomes modulate the metabolic status of the distant pre-metastatic niche to promote metastasis. Citation Format: Jinlu Dai, Yi Lu, Jian Zhang, Evan Keller. Prostate cancer-derived exosomes alter the metabolic microenvironment of bone marrow pre-metastatic niche through PKM2 to promote bone metastasis. [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 1567.
Differential expression of PD-L1 expression in high grade T1 (HGT1) v. muscle invasive urothelial carcinoma (MIUC) and its prognostic implications.
Authors: Stephanie A. Mullane, Lillian Werner, Anna Orsola, Jesse Novak, Toni K. Choueiri, Gordon J. Freeman, Sabina Signoretti, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2016)

4535 Background: Programmed death-1 (PD-1) receptor negatively regulates T cell-mediated responses.PD-1 ligand (PD-L1) can be expressed on both tumor cells and mononuclear (MNC) infiltrates in MIUC. Increased MNC PD-L1 positive (PD-L1+) staining is correlated with better overall survival in metastatic UC. Several trials are now exploring the role of checkpoint inhibitors in non-MIUC (NMIUC). However, differences in PD-L1 expression between NMIUC (such as HGT1 tumors) and MIUC remain unknown. Methods: Formalin-fixed paraffin embedded (FFPE) tumor samples from 109 clinically annotated HGT1 UC patients (pts) were retrieved. All pts were initially diagnosed with HGT1 UC by transurethral resection (TUR), subsequently received BCG, and were followed for a median of 7.4 years. PD-L1 expression was evaluated by immunohistochemistry using a mouse monoclonal anti-PD-L1 antibody (405.9A11). The assay was validated using FFPE cell line controls known to be positive or negative for PD-L1 expression by flow cytometry. PD-L1+ was defined as ≥ 5% tumor cell membrane staining. MNC PD-L1 expression was scored based on the extent of infiltrate and percentage of positive cells. Fisher’s exact tests assessed the associations of disease outcome (no recurrence, recurrence, or progression) with MNC presence, PD-L1+ MNC, and PD-L1+ tumor cells. Comparison analysis with PD-L1 expression results in MIUC is presented. Results: Among 109 HGT1 NMIUC pts, PD-L1+ expression in tumor cells was seen in 6 (6%) pts and in MNC in 40 (38%) pts. PD-L1+ expression was not correlated with disease outcomes in tumor cells (p = 0.3) nor in MNC (p = 0.47). The pattern of PD-L1 staining in tumor cells (but not MNC) was significantly different when comparing MIUC and HGT1, with less positivity seen in HGT1 tumors (p = 0.001). Among three patients who had paired TUR and cystectomy samples, one patient changed from negative to positive PD-L1 MNC. Conclusions: PD-L1 is widely expressed in MNC, but not in tumor cells in HGT1 NMIUC with no correlation to recurrence or progression to muscle invasion. PD-L1 expression in tumor cells is significantly higher in MIUC compared to HGT1 NMIUC.
Prevalence of Diabetes in Adolescents Aged 12 to 19 Years in the United States, 2005-2014
Authors: Andy Menke, Sarah Casagrande, Catherine C. Cowie
Journal: JAMA (2016)

Li Wang, PhD; Xiaoguang Li, PhD; Zhaoxin Wang, PhD; Michael P. Bancks, PhD; Mercedes R. Carnethon, PhD; Philip Greenland, MD; Ying-Qing Feng, MD; Hui Wang, MD, PhD; Victor W. Zhong, PhD
Incidence and Risk Factors for Hemorrhagic Cystitis in Adult Patients Undergoing Allogeneic Stem-Cell Transplantation.
Authors: Pau Montesinos, Mari-Liz Paciello, Susana Cantero, Jaime Sanz, Ignacio Lorenzo, Federico Moscardo, Guillermo Martin, Leonor Senent, Noemi Puig, Margarita Blanes, Lorenzo Algarra, Javier de la Rubia, Miguel Sanz, Guillermo Sanz
Journal: Blood (2006)
256P To compare the efficacy and safety of pazopanib and sunitinib in metastatic renal cell carcinoma (RCC) of Chinese population
Authors: M.F.T. Chan, Q.Y.N. Lam, V.H.F. Lee, S.W.K. Siu, P.W.K. Kwong, T.W. Leung
Journal: Annals of Oncology (2015)
Abstract 4505: Pan-cancer analysis of fusion gene druggability and neoantigen potential
Authors: Henrik Edgren, Anja Ruusulehto, Kalle Ojala, Maria Laaksonen
Journal: Cancer Research (2016)

Abstract Fusion genes are a well known type of oncogenic mutation, in which a genomic rearrangement, such as e.g. a translocation, inversion or deletion, joins together parts of two genes, which normally are not located adjacent to each other. In the context of cancer driver mutations, the result of this rearrangement is a novel chimeric gene with oncogenic potential. While fusion genes have been known longest in hematological malignancies, over the last years they have been shown to occur in nearly all types of cancers studied. Notable examples include ETS-family fusions, such as TMPRSS2-ERG, in prostate cancer. In previous work, we have used our FusionSCOUT fusion gene detection pipeline to analyze over 8000 cancer samples from 28 different TCGA cancer types. In this study, we extend this target discovery to further characterize the genomic alteration contexts in which gene fusions occur, both by examining the copy number states at inferred rearrangement breakpoints, as well as by correlating the numbers of fusion genes identified in tumors with the level of genomic instability in the tumors. We also analyze the frequency at which different druggable protein domains occur in fusion genes, comparing these to the expected random distribution. Finally, we predict, for each tumor, the neoantigen potential of the identified fusion proteins and compare this to the same predictions for simple somatic mutations, in order to characterize the contribution of fusion proteins to neoantigen load. In summary, we extend our pan-cancer fusion gene identification analysis with a detailed characterization of the genomic alteration contexts at which fusion genes occur. We also report on the drug treatment potential of fusion genes, both in terms of small molecule drugs, as well as highlight the degree to which fusion gene derived chimeric proteins should be taken into account when estimating the neoantigen load of tumors. Citation Format: Henrik Edgren, Anja Ruusulehto, Kalle Ojala, Maria Laaksonen. Pan-cancer analysis of fusion gene druggability and neoantigen potential. [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 4505.
Abstract 18046: Emergency Coronary Artery Bypass Grafting for Cardiogenic Shock Complicating Acute Myocardial Infarction is Associated With Satisfactory Long-term Outcomes in Hospital Survivors
Authors: Piroze M Davierwala, Alexander Verevkin, Sergey Leontyev, Ardawan J Rastan, Matthias Mohr, Farhad Bakhtiary, Martin Misfeld, Friedrich W Mohr
Journal: Circulation (2015)

Introduction: Cardiogenic shock (CS), which is one of the most dreadful complications following acute myocardial infarction (AMI), is an indication for emergent coronary artery bypass graft surgery (CABG) in patients not amenable for percutaneous coronary intervention. Our study aimed to identify risk factors for 30-day and long-term mortality in patients presenting with AMI complicated by CS requiring emergency CABG. Methods: Preoperative characteristics, operative parameters, and postoperative outcomes were prospectively collected for 508 patients undergoing CABG for CS complicating AMI (ST-elevation MI [STEMI]:42.9%;non-STEMI:57.1%) in our database between January 2000 and June 2014. Predictors of 30-day and long-term mortality were identified by logistic and Cox regression analyses, respectively. Results: Mean age was 69±10 years. 78.3% of patients had 3-vessel and 47% left main disease. Almost 50% of patients had left ventricular function &lt;30% with 29.6%, 37.9%, 46.7% and 9.8% requiring preoperative resuscitation, ventilator, intra-aortic balloon pump and extracorporeal membrane oxygenation support (ECMO), respectively. 30-day mortality was 31.9% and was independently predicted by peripheral vascular disease [PVD] (odds ratio [OR]:1.8; 95% confidence interval [CI]:1.1-2.9;p=0.02), STEMI (OR:1.9;95%CI:1.2-2.8;p=0.004), lactate levels &gt;4mmol/l (OR:3.3;95%CI:1.7-6.5;p&lt;0.0001) and ECMO support (OR:5.0;95%CI:2.6-9.9;p&lt;0.0001). Cumulative survival was 51% at 1 year, 44% at 3 years and 33% at 5 years and correspondingly improved to 74%, 64% and 48%, when 30-day mortality was excluded from the analysis. Incremental age (OR:1.04,p&lt;0.0001), STEMI (OR:1.3,p=0.02), PVD (OR:1.4,p=0.03), diabetes (OR:1.5,p=0.001), lactate levels &gt;4mmol/l (OR:2.3,p&lt;0.0001) and high preoperative inotropic (OR:1.3,p=0.02), and ECMO support (OR:3.3,p&lt;0.0001) predicted late mortality. Conclusion: Emergency CABG in patients with AMI complicated by CS was associated with high 30-day mortality, which was independently predicted by severe preoperative hemodynamic instability and presence of STEMI. Satisfactory long-term survival is observed in patients who survived the operation, demonstrating the benefit of emergency CABG.
Unusual Diversity of Myoglobin Genes in the Lungfish
Authors: Jonas Koch, Julia Lüdemann, Rieke Spies, Marco Last, Chris T. Amemiya, Thorsten Burmester
Journal: Molecular Biology and Evolution (2016)

Myoglobin is a respiratory protein that serves as a model system in a variety of biological fields. Its main function is to deliver and store O2 in the heart and skeletal muscles, but myoglobin is also instrumental in homeostasis of nitric oxide (NO) and detoxification of reactive oxygen species (ROS). Almost every vertebrate harbors a single myoglobin gene; only some cyprinid fishes have two recently duplicated myoglobin genes. Here we show that the West African lungfish Protopterus annectens has at least seven distinct myoglobin genes (PanMb1–7), which diverged early in the evolution of lungfish and showed an enhanced evolutionary rate. These myoglobins are lungfish specific, and no other globin gene was found amplified. The myoglobins are differentially expressed in various lungfish tissues, and the brain is the main site of myoglobin expression. The typical myoglobin-containing tissues, the skeletal muscle and the heart, have much lower myoglobin mRNA levels. Muscle and heart express distinct myoglobins (PanMb1 and PanMb3, respectively). In cell culture, lungfish myoglobins improved cellular survival under hypoxia albeit with different efficiencies and reduced the production of reactive oxygen species. Only Mb2 and Mb6 enhanced the energy status of the cells. The unexpected diversity of myoglobin hints to a functional diversification of this gene: some myoglobins may have adapted to the O2 requirements of the specific tissue and help the lungfish to survive hypoxic periods; other myoglobins may have taken over the roles of neuroglobin and cytoglobin, which appear to be missing in the West African lungfish.
Abstract 2581: Determinants for compliance to colorectal cancer screening in Korea: A multilevel analysis
Authors: Aesun Shin, Hyeongtaek Woo
Journal: Cancer Research (2016)

Abstract BACKGROUND: This study aimed at investigating the individual and area level factors associated with colorectal cancer screening attendance. METHODS: Colorectal cancer screening participation as well as other individual level data were gathered from the fifth Korea National Health and Nutrition Examination Survey, 2010-2012. The area level data were extracted from 2009 Health promotion strategies and programs development for health inequalities alleviation (Shin et al.,2009). Multilevel model was used for data analysis. RESULTS: Information on a total of 8,783 individuals (3,777 men and 5,006 women) aged 50 years and older and deprivation index of each areas were used in the final analysis. Among individual level variables, men were more likely to participated in colorectal cancer screening within 5 years than women (58.0% for men vs 53.9% for women)(Odds Ratio (OR) = 0.85; 95% CI 0.73 to 0.99), and highest among age 60-69 (63.3%). Area level variables's explained class-level variance was 6.4%. CONCLUSION: In this study, by applying the multilevel analysis we can find that colorectal cancer screening attendance rate is associated with both individual and community factors. Citation Format: Aesun Shin, Hyeongtaek Woo. Determinants for compliance to colorectal cancer screening in Korea: A multilevel analysis. [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 2581.
Caution is urged over “game changing” asthma drug
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Research commentators have urged caution over the results of a study of a new asthma drug that has been hailed as a “game changer,” saying that much larger trials are needed.

Last weekend newspapers carried stories with headlines such as, “Asthma pill provides hope to millions of sufferers and could replace inhaler,”1 “Asthma drug ‘game changer’ could revolutionise treatment,”2 and “First new asthma pill in 20 years hailed as ‘wonder drug’ by sufferers.”3

A press release from the University of Leicester, UK, which led the research, described fevipiprant, a prostaglandin D2 receptor 2 (DP2 receptor) antagonist, as “The first new asthma pill for nearly 20 years [that] has the power to significantly reduce the severity of the condition.”4

It reported the findings of a trial in 61 …
Abstract 423A: A tumor-associated mRNA localizing in circulating exosomes as a novel serological marker for pancreatic cancer: the retrospective clinical study
Authors: Keisuke Taniuchi
Journal: Cancer Research (2016)

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death in the Western world. Early diagnosis of PDAC is difficult, and no biomarkers in blood can identify patients with pancreatic cancer at an early stage. Serum cancer antigen 19-9 (CA19-9) remains the gold standard serum marker for patients with PDAC; however, inadequate sensitivity and specificity limit the use of CA19-9 in the early diagnosis of PDAC. Therefore, the discovery of biomarkers derived from blood that facilitate the distinction of PDAC would greatly affect patient management. Exosomes are extracellular lipid microvesicles, secreted by nearly all cells in body fluids such as peripheral blood. The exosome-associated RNA is called exosomal shuttle RNA that includes microRNAs and messenger RNAs (mRNAs). Methods: The aims of the present study are to assess if the mRNA that we found in the intracellular exosomes of PDAC cells is secreted from PDAC cells, and it is useful as a serum diagnostic marker for differentiating PDAC from individuals without pancreatic disorders compared with CA19-9. 20 PDAC patients (stage III: n = 5, stage IVa: n = 7 and stage IVb: n = 8 according to the classification of pancreatic carcinoma of the Japan Pancreas Society) and 30 control individuals without pancreatic diseases were analyzed in a retrospective cohort study. Circulating exosomes were isolated from serum, and then the mRNA localizing in exosomes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results: We confirmed that the mRNA was localized in secreted exosomes from cultured PDAC cells: a moderately differentiated PDAC cell line (S2-013) by the use of condition media real-time RT-PCR. Furthermore, the retrospective clinical study showed that the area under the curve (AUC) of reciever operating characteristic curves (ROC curves) was 0.805 (95%CI 0.691-0.9199) for this RNA and 0.8 (95%CI 0.675-0.926) for CA19-9. If the mRNA was combined with serum CA19-9, the AUC increased (0.921 [95%CI 0.851-0.991]). Conclusions: Our data suggest that measuring the level of this exosome-associated mRNA has the potential to improve detection of PDAC. Further research is necessary to understand whether this mRNA has clinical implications for early detection of PDAC (stage I and II) and how much this information adds to serum CA19-9. Citation Format: Keisuke Taniuchi. A tumor-associated mRNA localizing in circulating exosomes as a novel serological marker for pancreatic cancer: the retrospective clinical 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 423A.
Value of early referral to improve fertility preservation outcomes in women with breast cancer.
Authors: K. Oktay, S. Lee, S. Ozkavukcu, E. Heytens, R. M. Alappat
Journal: Journal of Clinical Oncology (2010)

9026 Background: ASCO recommends that young cancer patients be referred to specialists for fertility preservation (FP) as soon as possible after the diagnosis, however, there is no data to directly support that recommendation. The purpose of this study was to determine if early referral improves FP outcomes in young women with breast cancer undergoing adjuvant chemotherapy and/or radiotherapy. Methods: We performed a secondary analysis of a prospective database (Controlled Ovarian Stimulation Treatment with Letrozole Supplementation Study, COST-LESS, JCO 2009) of 154 women with breast cancer undergoing ovarian stimulation (OS) for FP by embryo or oocyte cryopreservation. Complete data were available in 93 patients with mean age of 35.2±4.4 years (range: 24 to 44). Results: Thirty-six of the 93 patients were referred and evaluated prior to breast surgery (PreS) and 57 post-surgery (PostS). PreS and PostS groups were similar in terms of age, cancer stage, and receptor or BRCA status. Likewise the mean number of oocytes or embryos cryopreserved per cycle were similar between the two groups. The time period from the first diagnosis date (FD) to initiation of OS was significantly shorter in patients who were referred PreS vs. PostS (43.0±28.0 vs. 72.5±30.6 days, p<0.001, Mann Whitney U test). There was, however, no difference in the length of time from FD to surgery date and from the date of first FP consultation to initiation of OS between the two groups. Six of 36 patients in the PreS group and 1 of 57 in the PostS group were able to undergo two FP cycles (p = 0.012, Fisher's exact test). This resulted in an additional 79 vs. 5 oocytes obtained in PreS vs PostS groups respectively. Patients who underwent first oocyte retrieval within 5 weeks of the surgery were able to complete a second cycle within 9 weeks of the surgery. Conclusions: Early referral prior to breast cancer surgery enables multiple cycles of FP without a delay in chemotherapy beyond 9 weeks post surgery. Women who can undergo multiple cycles may be at an advantage for FP because of additional number of eggs/embryos cryopreserved. This is the first study demonstrating the benefit of early FP referral in cancer patients. Practitioners should adhere to FP guidelines issued by ASCO in 2006. No significant financial relationships to disclose.