tbuckley/cabot-search huggingface dataset:
Inhibition of the EGFR/STAT3/CEBPD Axis Reverses Cisplatin Cross-resistance with Paclitaxel in the Urothelial Carcinoma of the Urinary Bladder
Authors: Wei-Jan Wang, Chien-Feng Li, Yu-Yi Chu, Yu-Hui Wang, Tzyh-Chyuan Hour, Chia-Jui Yen, Wen-Chang Chang, Ju-Ming Wang
Journal: Clinical Cancer Research (2016)

Cisplatin (CDDP) is frequently used in combination chemotherapy with paclitaxel for treating urothelial carcinoma of the urinary bladder (UCUB). CDDP cross-resistance has been suggested to develop with paclitaxel, thus hindering successful UCUB treatment. Therefore, elucidating the mechanisms underlying CDDP-induced anticancer drug resistance is imperative and may provide an insight in developing novel therapeutic strategy.Loss-of-function assays were performed to elucidate the role of the EGFR and STAT3 in CDDP-induced CCAAT/enhancer-binding protein delta (CEBPD) expression in UCUB cells. Reporter and in vivo DNA-binding assays were employed to determine whether CEBPD directly regulates ATP binding cassette subfamily B member 1 (ABCB1) and ATP binding cassette subfamily C member 2 (ABCC2) activation. Finally, a xenograft animal assay was used to examine the abilities of gefitinib and S3I-201 (a STAT3 inhibitor) to reverse CDDP and paclitaxel sensitivity.CEBPD expression was maintained in postoperative chemotherapy patients, and this expression was induced by CDDP even in CDDP-resistant UCUB cells. Upon CDDP treatment, CEBPD activated ABCB1 and ABCC2. Furthermore, the EGFR/STAT3 pathway contributed to CDDP-induced CEBPD expression in UCUB cells. Gefitinib and S3I-201 treatment significantly reduced the expression of CEBPD and enhanced the sensitivity of CDDP-resistant UCUB cells to CDDP and paclitaxel.Our results revealed the risk of CEBPD activation in CDDP-resistant UCUB cells and suggested a therapeutic strategy for patients with UCUB or UCUB resisted to CDDP and paclitaxel by combination with either gefitinib or S3I-201. Clin Cancer Res; 23(2); 503-13. ©2016 AACR.
Abstract 2452: Exosomes as mediators of paracrine signalling that promote invasive behavior in rhabdomyosarcoma
Authors: Sandra E. Ghayad, Ghina Rammal, Farah Ghamloush, Hussein Basma, Raya Saab
Journal: Cancer Research (2016)

Abstract Exosomes are small membranous vesicles secreted into body fluids by multiple cell types, including tumor cells. Tumor exosomes contain intact and functional protein, mRNA and miRNA that may alter the cellular environment to favor tumor growth. Rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue tumor, with two distinct subtypes, alveolar (ARMS) and embryonal (ERMS) histology. ARMS tumors are characterized in the majority of cases by a fusion oncoprotein PAX3-FOXO1, thought to be an initiating factor in tumorigenesis. To date, no studies have been performed to investigate the possible role or content of exosomes in paracrine signaling in RMS. In the present study, we isolated and characterized exosomes secreted from RMS cells, using 3 ERMS (fusion oncoprotein negative) and 2 ARMS (fusion oncoprotein positive) cell lines. RNA analysis showed that small RNA were enriched in RMS-derived exosomes, therefore we focused on evaluating the miRNA content. Array expression analysis showed that exosome miRNA clustered together well, and to a higher extent than cellular miRNA, in ARMS cell lines. Similarly, in the 2 ERMS cell lines that had mutant p53, exosome miRNA clustered together and the pattern of expression was very different from the corresponding cellular miRNA. ARMS and ERMS exosome-enriched miRNA were different, and only 2 miRNA were found to be common among both; putative targets are implicated in cancer and inflammation. Functionally, using in vitro assays, we found that both ERMS- and ARMS-derived exosomes significantly increased the cellular migration and invasion of normal human fibroblasts, and had a positive effect on viability and proliferation of both fibroblasts and RMS cells. In vivo, Matrigel plug assay showed that RMS-derived exosomes had a positive effect on the migration and invasion of stromal cells, suggesting a positive role on angiogenesis. We conclude that RMS-derived exosomes can exert specific paracrine effects on recipient cells, enhancing cell viability as well as invasive properties of fibroblasts and stromal cells, and therefore is likely to play a role in promoting RMS angiogenesis and metastasis. Ongoing studies are aimed at directly assessing the role of RMS-derived exosomes in clinical angiogenesis and metastasis, using in vivo murine models, in addition to dissecting the role of specific enriched miRNA on recipient cell biology. Citation Format: Sandra E. Ghayad, Ghina Rammal, Farah Ghamloush, Hussein Basma, Raya Saab. Exosomes as mediators of paracrine signalling that promote invasive behavior in rhabdomyosarcoma. [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 2452.
Platinum retreatment in second line chemotherapy for metastatic urothelial carcinoma (UC): Assessing the concept of platinum sensitivity and predictors of survival.
Authors: Mohammad Ma'koseh, Hiroshi Kitamura, Sandy Srinivas, Jeremy Howard Lewin, Samer Salah
Journal: Journal of Clinical Oncology (2016)

e16024 Background: Although there is no uniform consensus about standard second-line chemotherapy for patients with metastatic UC, retreatment with second line platinum-based regimens (SLPR) is commonly practiced. This study aimed to identify factors predicting survival in SLPR including the concept of platinum sensitivity. Methods: Pooled data of patients at three institutions with metastatic UC treated with SLPR for disease progression following standard first-line platinum regimens was assessed. The influence of potential prognostic factors on overall survival (OS) including the platinum-free interval (PFI) (defined as the interval from completion of the first-line to initiation of second-line platinum-based therapy), were assessed through univariate and multivariate Cox-regression analysis. Results: A total of 51 patients were eligible for analysis. SLPR differed from first-line in 45 patients (88%): nedaplatin (25 patients); carboplatin (11 patients); oxaliplatin (10 patients); and cisplatin (5 patients). Eighteen patients (35%) had objective response to first-line platinum regimens, whereas 16 (31%) had objective response to second-line (1 CR (2%); 15 PR (29%); 13 SD (25%); 17 PD (33%); Unknown (12%)). The median progression free survival (PFS) and OS from second-line treatment were 5.0 and 10.3 months respectively. The PFI did not predict PFS (median PFS, 4.2 and 5.3 months for interval < and ≥ 6 months respectively, p= 0.65) or OS (median OS, 10.3 and 9.8 months for interval < and ≥ 6 months respectively, p = 0.73). In multivariate analysis, liver metastasis (HR 4.17, 95% CI: 1.67-10.31, p = 0.004) and ECOG PS ≥ 1 (HR: 2.19, 95% CI: 1.04 – 4.61, p = 0.04) were the only independent factors for inferior OS. Conclusions: Although 31% of patients had objective response with platinum retreatment, the PFI was not predictive of survival in UC. Liver metastasis and ECOG PS were predictors of inferior survival in this patient population. Further studies are required to identify those who may benefit from SLPR.
Risk of solid cancer, cardiovascular disease, anaphylaxis, osteoporosis and fractures in patients with systemic mastocytosis: A nationwide population‐based study
Authors: Sigurd Broesby‐Olsen, Dóra Körmendiné Farkas, Hanne Vestergaard, Anne Pernille Hermann, Michael Boe Møller, Charlotte Gotthard Mortz, Thomas Kielsgaard Kristensen, Carsten Bindslev‐Jensen, Henrik Toft Sørensen, Henrik Frederiksen
Journal: American Journal of Hematology (2016)

In patients with systemic mastocytosis (SM), several aspects of morbidity remain poorly understood. We assessed the risk of solid cancers, cardiovascular disease, anaphylaxis, osteoporosis, and fractures in SM patients. Using Danish medical registries, we conducted a nationwide population-based cohort study including 687 adult (≥15 years) SM patients diagnosed during 1997-2012. A comparison cohort of 68,700 subjects from the general Danish population who were alive and without SM at the given SM subject's diagnosis were age- and gender-matched. Outcomes were a new diagnosis of solid cancer, venous thromboembolism (VTE), myocardial infarction (MI), stroke, anaphylaxis, osteoporosis, or fracture. For solid cancers the hazard ratio (HR) was 2.4 (95% confidence interval [CI] 1.9-2.8) with a 10-year absolute risk (AR) in the SM-cohort of 12.6% (95% CI 9.4-16.3). Specifically, we found a HR of 7.5 (95% CI 4.4-13.0) for melanoma and a HR of 2.5 (95% CI 1.7-3.5) for non-melanoma skin cancers (NMSCs). For VTE we found a HR of 1.9 (95% CI 1.2-3.0), with a 10-year AR of 3.9% (95% CI 2.3-6.1); for MI a nonsignificant increased HR of 1.4 (95% CI 0.9-2.3), with a 10-year AR of 1.8% (95% CI 0.9-3.2); and for stroke a HR of 1.6 (95% CI 1.1-2.3) with a 10-year AR of 4.6% (95% CI 2.8-6.9). The HR for anaphylaxis was 7.2 (95% CI 5.3-9.9), and the 10-year AR was 3.1% (95% CI 1.9-4.9). For osteoporosis the HR was 3.6 (95% CI 2.7-4.6) with a 10-year AR of 7.2% (95% CI 5.2-9.8). For fractures the HR was 1.2 (95% CI 0.9-1.6) and the 10-year AR was 5.9% (95% CI 3.9-8.4). SM patients are at increased risk of solid cancers - especially melanoma and NMSC-and cardiovascular disease. The risk of anaphylaxis and osteoporosis is clearly increased in SM, though absolute risk was low in this population-based study. The fracture-risk was only slightly increased. Am. J. Hematol. 91:1069-1075, 2016. © 2016 Wiley Periodicals, Inc.
Abstract 3456: Polychlorinated biphenyls and relative telomere length in the Anniston Community Health Survey: A cross-sectional study
Authors: Catherine Callahan, Marian Pavuk, Xuefeng Ren, James R. Olson, Matthew R. Bonner
Journal: Cancer Research (2016)

Abstract Background: Polychlorinated biphenyls (PCBs) exposure is associated with increased risk of melanoma and non-Hodgkin lymphoma in some, but not all, epidemiologic studies. Although the carcinogenic mechanisms of specific PCB congeners remain to be fully explained, PCBs have been demonstrated to induce oxidative stress and inflammation and therefore may have deleterious impacts on telomere length. We investigated the association between serum concentrations of PCBs and telomere length in a highly exposed population. Methods: The Anniston Community Health Survey (ACHS) is a cross-sectional study of 766 residents of Anniston, Alabama conducted between 2005 and 2007. We measured relative telomere length (RTL) with telomere/single copy gene ratio, in DNA extracted from peripheral blood samples in a subset of 57 African-American and 46 white participants, using monochrome multiplex quantitative polymerase chain reaction. We used multiple linear regression to estimate the association between 27 individual PCB congeners, and sum PCBs, adjusting for age, plate, and total lipids. All analyses were stratified by race. PCBs and RTL were log-transformed. Results: ACHS participants had high serum concentrations of PCBs (mean sum PCBs among African-Americans = 14,687.69 ppt whole weight, SD = 23,515.46; mean sum PCBs white participants 6,088.32 ppt whole weight, SD = 8,750.57). RTL did not differ by race (mean RTL African-Americans = 0.94 SD = 0.08; mean RTL whites = 0.94, SD = 0.09). Among African-American participants, sum serum PCBs was not associated with RTL (0.70% per 100 ppt; 95% confidence interval = -9.43, 19.70). However, PCB 167 was weakly associated with higher RTL (2.35%, 95%CI = -8.56, 14.55), while PCB 157 was associated with shorter RTL (-4.36%; 95%CI = -15.63, 8.40). Among white participants, a 100 ppt increase in sum serum PCBs was associated with a 10.20% increase in RTL (95% CI = -7.10, 30.72). PCB 138, in particular, was associated with increased RTL among white participants (16.29%; 95% CI = 1.34, 33.46). Conversely, PCB 189 was associated with shorter RTL among white participants (-10.48%; 95%CI = -29.82, 14.19). Conclusions: We did not observe consistent associations between serum concentrations of PCBs and RTL, suggesting that the association may vary by race and be congener specific. Our results are necessarily preliminary and are limited by the small number of participants. Additional measurements of RTL among ACHS participants are on-going. Citation Format: Catherine Callahan, Marian Pavuk, Xuefeng Ren, James R. Olson, Matthew R. Bonner. Polychlorinated biphenyls and relative telomere length in the Anniston Community Health Survey: A cross-sectional 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 3456.
Correction: Androgen-Induced <i>TMPRSS2:ERG</i> Fusion in Nonmalignant Prostate Epithelial Cells
Journal: Cancer Research (2011)

In this article (Cancer Res 2010;70:9544–8), which was published in the December 1, 2010 issue of Cancer Research (1), there is a typographical error in the name of the first author. The correct name is Nuria Coll-Bastus.
Abstract 1670: Radiosensitization of glioma cells by the ketone body β-hydroxybutyrate is associated with enhanced cell cycle arrest in the G2/M phase
Authors: Helena B. Silva-Nichols, Alex P. Rossi, Eric C. Woolf, Marshall J. Fairres, Loic P. Deleyrolle, Brent A. Reynolds, Adrienne C. Scheck
Journal: Cancer Research (2016)

Abstract Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with a 5 year survival rate of 25% in children and less than 10% in adults. Improvement in the prognosis of GBM patients requires the development of new therapeutic approaches. One emerging strategy is to target aberrant cell metabolism, a trait shared by virtually all tumor cells. The ketogenic diet (KD), a high fat, low carbohydrate and protein metabolic therapy has been shown to prolong survival in animal glioma models, and when used in conjunction with radiation cured 9 of 11 mice of their implanted tumors. We have also shown that the KD alters hypoxia, angiogenesis, and other hallmarks of glioma progression. To elucidate the underlying mechanisms through which ketones exert their effects on glioma, we are doing analyses of the effect of β-hydroxybutyrate (βHB), the most prevalent ketone body synthesized during ketosis, on glioma cells in vitro. We found that βHB both alone and in conjunction with radiation significantly inhibits proliferation of human and mouse glioma cells and human glioma stem cells (GSC). Alterations in passage through the cell cycle may affect proliferation, and cells are also more sensitive to radiation in the G2/M cell cycle phase. We therefore analyzed the effect of βHB on cell cycle distribution of cells treated with βHB and/or radiation. An analysis of cell cycle status by flow cytometry demonstrated that treating the GSC line L0 with 5mM βHB in combination with 4 Gy of radiation significantly increased the number of cells in G2/M cell cycle arrest. In GL261-Luc2 mouse glioma cells, 5mM βHB alone significantly enhanced G2/M cell cycle arrest, which could lead to radiosensitization. Currently we are analyzing proteins involved in cell cycle progression and apoptosis to better understand βHB mediated changes in growth and radioresistance. In summary, these data provide insight to the radiosensitization and anti-proliferative mechanisms of βHB and may hold implications for the use of the KD in the treatment of GBM. Citation Format: Helena B. Silva-Nichols, Alex P. Rossi, Eric C. Woolf, Marshall J. Fairres, Loic P. Deleyrolle, Brent A. Reynolds, Adrienne C. Scheck. Radiosensitization of glioma cells by the ketone body β-hydroxybutyrate is associated with enhanced cell cycle arrest in the G2/M phase. [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 1670.
Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non-Alzheimer's disease pathophysiology (SNAP) or Alzheimer's disease pathology: a longitudinal study
Authors: Samantha C Burnham, Pierrick Bourgeat, Vincent Doré, Greg Savage, Belinda Brown, Simon Laws, Paul Maruff, Olivier Salvado, David Ames, Ralph N Martins, Colin L Masters, Christopher C Rowe, Victor L Villemagne
Journal: The Lancet Neurology (2016)
ST Elevation During Open Heart Surgery
Authors: Ken-ichi Komukai, Keiji Hirooka, Manabu Taneike, Yoshinori Yasuoka, Hiroyoshi Yamamoto, Katsuji Hashimoto, Wakatomi Chin, Yukihiro Koretsune, Hideo Kusuoka, Yoshio Yasumura
Journal: Circulation (2005)
Hodgkin's Disease
Authors: Walter J. Urba, Dan L. Longo
Journal: New England Journal of Medicine (1992)

IN 1992, approximately 75 percent of all patients who present with Hodgkin's disease should be cured of their disease. This result will be achieved only with the careful application of appropriate staging techniques and treatment methods.Cell of OriginHodgkin's disease is unusual in that the bulk of the tumor is composed of normal cells within which the malignant Reed–Sternberg cells are found. The cellular origin of the neoplastic cell remains controversial.1 The Reed–Sternberg cells in all the histologic subtypes usually express antigens found on resting or activated lymphocytes. These include CD30 (Ki-1, Hefi-1), CD25 (interleukin-2 receptor), HLA-DR, and CD71 . . .
Reduced CD161+ MAIT cell frequencies in HCV and HIV/HCV co-infection: Is the liver the heart of the matter?
Authors: Johanna M. Eberhard, Silke Kummer, Philip Hartjen, Anja Hüfner, Tom Diedrich, Olaf Degen, Ansgar W. Lohse, Jan van Lunzen, Julian Schulze zur Wiesch
Journal: Journal of Hepatology (2016)
Efficacy and Safety of Liraglutide Added to Capped Insulin Treatment in Subjects With Type 1 Diabetes: The ADJUNCT TWO Randomized Trial
Authors: Bo Ahrén, Irl B. Hirsch, Thomas R. Pieber, Chantal Mathieu, Fernando Gómez-Peralta, Troels Krarup Hansen, Areti Philotheou, Sune Birch, Erik Christiansen, Thomas Jon Jensen, John B. Buse
Journal: Diabetes Care (2016)

OBJECTIVE To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS A 26-week, placebo-controlled, double-blind, parallel-group trial enrolling 835 subjects randomized 3:1 receiving once-daily subcutaneous liraglutide (1.8, 1.2, and 0.6 mg) or placebo added to an individually capped total daily dose of insulin. RESULTS Mean baseline glycated hemoglobin (HbA1c) (8.1% [65.0 mmol/mol]) was significantly decreased with liraglutide versus placebo at week 26 (1.8 mg: –0.33% [3.6 mmol/mol]; 1.2 mg: –0.22% [2.4 mmol/mol]; 0.6 mg: –0.23% [2.5 mmol/mol]; placebo: 0.01% [0.1 mmol/mol]). Liraglutide significantly reduced mean body weight (–5.1, –4.0, and –2.5 kg for 1.8, 1.2, and 0.6 mg, respectively) versus placebo (–0.2 kg). Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo. There were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year; P = 0.03) with liraglutide 1.2 mg vs. placebo and of hyperglycemia with ketosis &amp;gt;1.5 mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year; P = 0.01). CONCLUSIONS In a broad population of subjects with long-standing type 1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg.
How Ovarian Cancer Evades Immune Scrutiny
Authors: Alissa Poh
Journal: Cancer Discovery (2016)

Although dendritic cells are abundant in ovarian tumors, scientists have been puzzled that these cells aren't immunostimulatory. New research reveals a role for the protein SATB1, which is transiently required during ovarian-associated dendritic cell maturation-its unremitting expression in these cells drives them to acquire an inflammatory, immunosuppressive phenotype.
Abstract 3970: Impact of endoscopic stent insertion on detection of viable circulating tumor cells for obstructing colon cancer
Authors: Shinya Yamashita
Journal: Cancer Research (2016)

Abstract The obstructive colorectal cancer(CRC) was reported to be 7-20% of CRC. For the patients (pts) with obstructive colorectal cancer, self-expanding metallic stents (SEMS) have been useful as a palliative treatment. Insertion of SEMS for obstructive colorectal cancer is used as a bridge to surgery approach. But suspicion have been raised about whether shear forces that act on the tumor during expansion of the stent may result in a release of cancer cells into the circulation (i.e., CTCs). This study was conducted to clarify whether insertion of colonic stents results in increased levels of viable CTCs (v-CTCs). For detecting viable CTCs(v-CTCs) of CRC, we employed a novel method, TelomeScan F35 detection system. The system was constructed with a GFP-expressing attenuated adenovirus, in which the telomerase promoter regulates viral replication. 7.5 ml of peripheral blood samples were obtained before and after stent insertion and after operation. GFP-positive and CD45-negative cells were counted as v- CTCs. This study was a single institution trial, approved by the Kure Medical Center IRB. Surgical operation was scheduled within 1 month after stenting. Between October 2013 and June 2015,10 pts aged 58-89 years (5 males and 5 females) were enrolled. The surgical operation (R0) was performed in 9 cases. CEA was reduced to &amp;lt;50% of baseline value in 6 of 9 measurable pts after resection. 6 pts had no v-CTCs before stenting. Among them, 3 pts had increasing number of 1-3 v-CTCs after stenting and 1 of them developed multiple liver metastasis 12 month after resection. While, 4 pts had v-CTCs (1-19 cells) before stenting and 3 of these 4 patients had significant increase of number of v-CTCs (1-21 cells) after stent insertion. 2 of them had 12 and 14 v-CTCs, respectively after operation, despite the normalized value of CEA. The present study suggested that endoscopic stent insertion may result in tumor cell dissemination into the peripheral circulation and may induce early distant metastasis. In conclusion, v-CTCs may become useful for prognosis assessment, especially when SEMS insertion is considered. Citation Format: Shinya Yamashita. Impact of endoscopic stent insertion on detection of viable circulating tumor cells for obstructing colon 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 3970.