tbuckley/cabot-search huggingface dataset:
Abstract 5100: Interplay between ECM stiffness, miR-203 and mammographic density
Authors: Ivory Dean, Irene Acerbi, Alfred Au, Yunn-Yi Chen, Shelley Hwang, Valerie Weaver
Journal: Cancer Research (2016)

Abstract High mammographic density (MD) is associated with a greater risk of breast cancer and is characterized by high extracellular matrix (ECM) collagen. Elevated collagen increases ECM stiffness and can promote the malignant transformation of oncogenically-primed mammary epithelial cells in culture and in vivo. Whether or not high MD reflects a breast stroma that is stiff and if ECM stiffness accounts for the elevated breast cancer risk in high MD tissue has yet to be resolved. To address this question we are conducting a comprehensive biophysical and molecular analysis of BIRADS status in prophylactic mastectomies in women with low (BIRADS 1) versus high MD (BIRADS 4). Data revealed that the intra-lobular ECM associated with the terminal end-buds contains anisotropic compliant and relaxed collagen fibrils. By contrast, the inter-lobular ECM contains stiff, oriented collagen fibrils. Preliminary data suggest that the ECM associated with the terminal end-buds in the upper outer quadrant may be stiffer in women with high MD as compared to low MD. These same tissues also expressed lower levels of the microRNA miR-203, which has been implicated in epithelial-to-mesenchymal transition (EMT) inhibition. Consistently, in vitro studies revealed that miR-203 was repressed in MECs cultured on a stiff ECM. We also found that a stiffened mammary ECM decreased miR-203 expression and promoted an EMT. Additionally, inhibiting ECM stiffening restored miR-203 levels and reduced an EMT. Moreover and importantly, we showed that triple negative breast tumors that often express EMT markers have reduced miR-203 levels. Studies are underway to elaborate these preliminary findings and to assess their clinical relevance. (This work is supported by the: NIH NSRA T32 CA 108462-11 to Ivory Dean, Susan G Komen PDF12230246 to Irene Acerbi, W81XWH-13-1-0216, USMRAA DOD-BCRP BC122990, NIH R01 CA138818-01A1 and NIH R01 CA192914-01 to Valerie Weaver.) Citation Format: Ivory Dean, Irene Acerbi, Alfred Au, Yunn-Yi Chen, Shelley Hwang, Valerie Weaver. Interplay between ECM stiffness, miR-203 and mammographic density. [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 5100.
Influence Of Steroid Exposure On CMV Specific T Cells Following Allogeneic Stem Cell Transplantation
Authors: Cornelia S. Link, Elke Rücker-Braun, Sebastian Tuve, Sarah Matko, Marc Schmitz, Rebekka Wehner, Antje Tunger, Katja Sockel, Stefani Parmentier, Jan Moritz Middeke, Änne Boldt, Johannes Schetelig, Markus Odendahl, Torsten Tonn, Martin Bornhäuser, Falk Heidenreich
Journal: Blood (2013)
Abstract 661: Establishment of transgenic mice with liver-specific BRAF V600E mutation
Authors: Hiroki Tanaka, Masahiro Yamamoto, Kosuke Yamazaki, Keiko Shimizu, Katsuhiro Ogawa
Journal: Cancer Research (2016)

Abstract Diethylnitrosamine (DEN) is often used to induce hepatocarcinogenesis in rodents to investigate the pathogenesis of hepatocellular carcinoma (HCC). BrafV637E mutation, corresponding to the human BRAFV600E mutation, is highly frequent in DEN-induced hepatic tumors depending on mouse strains. To investigate the role of BrafV637E mutation in DEN-induced hepatocarcinogenesis, we established the transgenic mice (Alb-Cre/BRAFV600E), in which human BRAFV600E mutation is specifically expressed in the liver, and compared the properties of DEN-induced hepatic tumors and the livers of the transgenic mice. The hepatic tumors were induced by neonatal treatment with DEN, isolated at various time points, and stored as frozen or paraffin-embedded materials. For production of the transgenic mice, we obtained homozygous male BRAFV600E mice, in which a LoxP-flanked cassette containing the human BRAF exons 15-18 cDNA, mouse polyadenilation sequences and the neo gene was inserted into the mouse Braf intron 14 upstream of the human BRAF exon 15 cDNA that encodes the BRAFV600E mutation, and crossed them with female Alb-Cre mice by in vitro fertilization. RT-PCR and cDNA sequencing revealed that the liver of Alb-Cre/BRAFV600E mice expressed mRNA derived both from normal mouse and mutated human BRAF exon 15. The transgenic mice showed 20% decrease in body weight compared to normal mice, but 5 fold-increase in the liver/body weight. Histological examination revealed that the liver was entirely consisted of basophilic hepatocytes resembling to those in DEN-induced foci of cellular alteration at 8 weeks of birth, and bile duct cells were further increased at 10-12 weeks. The Ki-67 labeling index of hepatocytes in the Alb-Cre/BRAFV600E mice was 3 times higher than normal mice. Immunoblot analysis revealed that the liver of Alb-Cre/BRAFV600E mice expressed the BRAFV600E protein and showed hyperphosphlylation of ERK1 and AktS473 like the DEN-induced hepatic tumors. Furthermore, immunohistochemical staining detected increased C5/C5a expression in the hepatocytes of Alb-Cre/BRAFV600E mice, and by immunoblot analysis C5a, a protease-cleaved form of C5, was specifically detected in Alb-Cre/BRAFV600E liver like DEN-induced tumors. These results indicate that the liver specific expression of mutationally-activated BRAF led to the hepatocytic phenotype mimicking the DEN-induced hepatic tumors. Citation Format: Hiroki Tanaka, Masahiro Yamamoto, Kosuke Yamazaki, Keiko Shimizu, Katsuhiro Ogawa. Establishment of transgenic mice with liver-specific BRAF V600E mutation. [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 661.
A Phase II Trial of FM (Oral Fludarabine and Mitoxantrone) Chemotherapy Followed by Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) for Previously Untreated Follicular Lymphoma (FL) Patients.
Authors: Pier Luigi Zinzani, Alessandro Pulsoni, Manuela Balocco, Monica Tani, Stefano Fanti, Alessio Perrotti, Paolo Castellucci, Francesco Zaja, Alberto Fabbri, Alfonso Zaccaria, Maria Teresa Voso, Pierpaolo Fattori, Luciano Guardigni, Patrizia Gentilini, Maria Giuseppina Cabras, Amalia De Renzo, Luigi Rigacci
Journal: Blood (2006)
No association between apolipoprotein E epsilon 4 allele and rate of decline in Alzheimer's disease
Authors: G M Murphy, J Taylor, H C Kraemer, J Yesavage, J R Tinklenberg
Journal: American Journal of Psychiatry (1997)

The relationship between number of apolipoprotein E epsilon 4 (APOE epsilon 4) alleles and the rate of cognitive decline in patients with Alzheimer's disease was examined.Rate of decline in score on the Mini-Mental State was measured during the active phase of the decline curve between Mini-Mental State scores of 23 and 0. To characterize onset, the authors also estimated for each subject the age at which the Mini-Mental State score fell below 23 and obtained a retrospective report of age at onset from the caregiver. The number of APOE epsilon 4 alleles carried by each subject was determined from genomic DNA samples. The study included 86 subjects with probable Alzheimer's disease who had had at least two cognitive evaluations (a mean of 5.6 evaluations per subject over an average period of 3.6 years).The results did not support an association between APOE epsilon 4 dosage and rate of cognitive decline. Age at onset and age at which the Mini-Mental State score fell below 23 were also not related to APOE epsilon 4 dosage. The APOE allele frequencies were similar to those in other studies of subjects with Alzheimer's disease, showing an enrichment of the epsilon 4 allele.Although the APOE epsilon 4 allele is a risk factor for Alzheimer's disease, there is no support of a strong association between APOE epsilon 4 dosage and rate of cognitive decline. The epsilon 4 allele did not predict age at onset. Methodological inconsistencies may account for discrepancies between these results and previous findings.
Effects of tofacitinib on cardiovascular risk factors and cardiovascular outcomes based on phase III and long-term extension data in patients with plaque psoriasis
Authors: Jashin J. Wu, Bruce E. Strober, Peter R. Hansen, Ole Ahlehoff, Alexander Egeberg, Abrar A. Qureshi, Debbie Robertson, Hernan Valdez, Huaming Tan, Robert Wolk
Journal: Journal of the American Academy of Dermatology (2016)
Evaluation of liver toxicity using Child-Pugh, MELD, and MELD-Na following stereotactic body radiation therapy (SBRT) of hepatocellular carcinomas.
Authors: Louis Lu, Eman ElAlfy, Daniel Wahl, Matthew H. Stenmark, Theodore Steven Lawrence, Mary Uan-Sian Feng
Journal: Journal of Clinical Oncology (2015)

365 Background: Radiation-induced liver disease (RILD) has been tracked when assessing the safety of fractionated liver radiotherapy. However, due to the rarity and severity of events, a more sensitive measure of liver damage is necessary. This study characterizes the time course of changes in generalizable measures of liver function as potential toxicity metrics. Methods: In this IRB-approved retrospective study, the records of 63 patients with 87 HCC tumors treated with SBRT at the University of Michigan between 2006 and 2012 were reviewed. Changes in Child-Pugh (CP), MELD, and MELD-Na were analyzed using the Student t test and chi-squared test. Results: 83% of the patients had cirrhosis, 62% hepatitis (hep) C, 7% hep B, 25% alcoholic, and 13% other. 83% had prior liver-directed therapy. 24% had &gt;1 tumor concurrently treated with SBRT. Median tumor size was 2.3 cm (0.7-10), gross tumor volume was 9.2 cc (0.6-469), and mean liver dose-GTV was 4.4 Gy (0-17.6 Gy). Prior to SBRT, 73% were CP A, 25% CP B, and 2% CP C. Median baseline CP, MELD, and MELD-Na were 5, 9, and 10. Mean CP increases after 3, 6, 9, and 12 months were 0.84, 1.79, 1.72, and 1.33; increases in MELD 1.47, 2.88, 5.38, and 3.91; increases in MELD-Na 1.45, 2.03, 4.24, and 2.48. All changes were significantly increased from baseline. On univariate analysis, &gt;1 tumor and cirrhosis predicted for a 1+ point increase in CP and &gt;1 tumor and higher mean liver dose-GTV for a 2+ point increase in CP. Older age, &gt;1 tumor, smaller GTV, and smaller max tumor dimension predicted for a 10+ point increase in MELD and &gt;1 tumor, hep C cirrhosis, and higher baseline MELD-Na for MELD-Na. Patients treated concurrently to &gt;1 tumor had greater increases in CP (3.60 vs. 0.81), MELD (9.33 vs. 1.97), and MELD-Na (8.47 vs. 2.19), p &lt; 0.0001 for all, compared to those with 1 tumor. No differences were seen with gender, portal vein thrombosis, number of prior treatments and baseline Child-Pugh classifications. Conclusions: We describe a time course and predictive factors for change in CP, MELD, and MELD-Na scores after SBRT for HCCs. These should be investigated further for potential use in toxicity modeling after incorporating dosimetric parameters.
Is the Use of DPP-4 Inhibitors Associated With an Increased Risk for Heart Failure? Lessons From EXAMINE, SAVOR-TIMI 53, and TECOS
Authors: Guntram Schernthaner, Avivit Cahn, Itamar Raz
Journal: Diabetes Care (2016)

About 40 years ago, the Framingham study first documented that the risk for heart failure (HF) in patients with diabetes was about twofold higher in men and fivefold in women compared with individuals without diabetes (1). The UK Prospective Diabetes Study (UKPDS) reported that the incidence of hospital admission for HF was similar to that of nonfatal myocardial infarction and nonfatal stroke (2). A more recent 6-year follow-up study of 65,619 patients with type 2 diabetes treated with insulin reported that the hospital admission rate due to HF (243 of 10,000) was higher than that due to myocardial infarction (97 of 10,000) or stroke (151 of 10,000) (3). The pathogenesis of HF in diabetes is multifactorial but can largely be attributed to four key factors: coronary artery disease (CAD), hypertension, diabetic cardiomyopathy, and extracellular fluid volume expansion (4,5). Remarkably, type 2 diabetes itself is a recognized risk factor for HF, independent of CAD and hypertension (4), suggesting that glycemic control may influence the development of HF. Hyperglycemia can exert deleterious effects on the myocardium and has been shown to increase oxidative stress, promote accumulation of advanced glycation end products, and cause interstitial fibrosis (6). Hyperglycemia has also been associated with myocardial lipotoxicity, mitochondrial dysfunction, abnormal substrate metabolism, and impaired calcium handling (7). Epidemiological evidence indicates that HbA1c and the risk of HF are significantly related. A cohort study of ∼49,000 patients with type 2 diabetes showed that each 1% increase in HbA1c was associated with an 8% increased risk of HF and that an HbA1c ≥10 relative to HbA1c <7 was associated with 1.56-fold (95% CI 1.26–1.93) greater risk of HF (8). A more recent meta-analysis (9) of 178,929 subjects with diabetes and 14,176 incident chronic HF cases showed an overall adjusted risk ratio …
Chronic Hemolytic Anemia in Two Patients Double Heterozygotes for Pyruvate Kinase and Another RBC Glycolitic Pathway Deficiency.
Authors: Serge Pissard, Nafa Saddedine, Aurelie Vasson, Marie-Odette Ballayguier, Frederic Galacteros, Henri Wajcman
Journal: Blood (2006)
Abstract 1656: Subtype-specific radiation response in human breast cancer and potential therapeutic effect of FAS death receptor modulation
Authors: Chen-Ting Lee, Yingchun Zhou, Kingshuk R. Choudhury, Sharareh Siamakpour Reihani, Mark W. Dewhirst, Janet K. Horton
Journal: Cancer Research (2016)

Abstract Breast cancer is the most common malignancy diagnosed among women worldwide and represents a heterogeneous group of subtypes. Radiation therapy is an important component of multimodal treatment for women with breast cancer. However, little is known about radiation response among these subtypes. Recent clinical data suggests that distinct patterns of response to systemic therapy may exist in association with each phenotype. Therefore, understanding the intrinsic variation of radiation response in breast cancer subtypes is important in prescribing individualized radiotherapy that maximizes the therapeutic ratio. Our previous studies have identified marked changes in gene expression in breast patient tumors and breast tumor cell lines in response to radiation. Among candidate genes, FAS was consistently and significantly induced after radiation in luminal breast tumors and cell lines. Modulation of FAS in basal breast cancer cell lines favorably impacted radiation response. In this study, we further investigated the role of FAS modulation and radiation response in a mouse model of breast cancer. MCF7 (luminal), HCC1954 (HER2+) or SUM159 (basal) cells were implanted orthotopically into the dorsal mammary fat pad of nude mice. These mice were then treated with different doses of radiation. Our results showed that radiation treatment inhibited MCF7, and to a less extent HCC1954 tumor growth in a dose-dependent manner, while SUM159 tumors were resistant to radiation. The estimated TCD50 value was 19.30 Gy for MCF7 and 44.88 Gy for SUM159. FAS was induced in MCF7 tumors after radiation but showed no change in SUM159 tumors. To investigate whether FAS modulation can affect radiation response, we silenced FAS in MCF7 tumors and activated FAS in SUM159 tumors. We found that silencing of FAS did not negatively impact radiation response in MCF7 tumors, possibly due to compensation by other apoptotic pathways. On the other hand, FAS activating antibody in combination with radiation delayed SUM159 and HCC1954 tumor growth (p = NS). In conclusion, these results suggest that there is intrinsic variation in radiation response among breast cancer subtypes. FAS concurrent with radiation slows tumor growth in the radiation resistant subtypes, but the effect was not significant. Alternative subtype-specific modulators of radiation response are under investigation. Citation Format: Chen-Ting Lee, Yingchun Zhou, Kingshuk R. Choudhury, Sharareh Siamakpour Reihani, Mark W. Dewhirst, Janet K. Horton. Subtype-specific radiation response in human breast cancer and potential therapeutic effect of FAS death receptor modulation. [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 1656.
P1147 : Validation of an alkaline phosphatase and bilirubin response criterion as biomarker for transplant-free survival in primary biliary cirrhosis in the world's two largest cohorts
Authors: M. Carbone, M.H. Harms, K. Lindor, G.M. Hirschfield, W.J. Lammers, M. Heneghan, H.L. Janssen, J.M. Neuberger, D. Thorburn, A. Pares, S. Sharp, P. Invernizzi, N. Warheam, A. Floreani, A. Bathgate, C. Corpechot, M. Aldersley, M. Mayo, N.F. LaRusso, F. Nevens, G.J. Alexander, K.V. Kowdley, R.N. Sandford, A.L. Mason, D. Jones, H.R. van Buuren, G. Mells, B.E. Hansen
Journal: Journal of Hepatology (2015)
Cost Implications of Using Different ECG Criteria for Screening Young Athletes in the United Kingdom
Authors: Harshil Dhutia, Aneil Malhotra, Vincent Gabus, Ahmed Merghani, Gherardo Finocchiaro, Lynne Millar, Rajay Narain, Michael Papadakis, Huseyin Naci, Maite Tome, Sanjay Sharma
Journal: Journal of the American College of Cardiology (2016)
Abstract 2376: Clonal evolution of skin carcinomas during tumor progression and metastasis
Authors: Melissa Q. McCreery, Allan Balmain
Journal: Cancer Research (2016)

Abstract Tumor heterogeneity and the ongoing evolution of tumor subpopulations have presented considerable challenges to the success of cancer therapies, highlighting a critical need for greater understanding of these phenomena. We used a K5CreER-Confetti reporter mouse in combination with the DMBA (dimethylbenzanthracene)/TPA (12-O-tetradecanoylphorbol-13-acetate) skin carcinogenesis model to study the genetics, clonality, and evolutionary behavior of tumor subpopulations from tumor initiation to metastasis. Treating the skin of K5CreER-Confetti mice with tamoxifen results in widespread labeling of the epidermis and hair follicles, which persists for at least 18 months. Papillomas that develop from Confetti-activated skin are of clonal origin, evidenced by each tumor being distinctly dominated by a single Confetti color (RFP, YFP, GFP, or CFP; or uncolored). Twelve weeks after initiation, the majority of tumors remain single-colored, with only 22% (36 of 133) showing any evidence of a secondary color population present. By 20 weeks after initiation, however, nearly all tumors (78%, 42 of 54) have incorporated one or more secondary populations, readily identifiable as streaks of a distinct color. FACS separation and sequencing of these different colored populations reveals these populations are genetically distinct: in preliminary analysis, the primary color population typically carries the expected driver Hras Q61L mutation while the secondary populations do not. The tumor thus appears to be incorporating pseudo-normal tissue from its microenvironment during early growth. Activation of the Confetti reporter in tumors post-initiation in papillomas results in labeling of single cells with all 4 Confetti colors, allowing subpopulations and their evolution to be studied at later stages. These highly multi-color papillomas subsequently give rise to single-color carcinomas and metastases, suggesting that the conversion from a benign to malignant tumor is clonally driven. The Confetti mouse is a valuable tool for studying the clonality and genetics of subpopulations present in tumors, which need to be better understood in order to improve the treatment of heterogeneous human tumors. Citation Format: Melissa Q. McCreery, Allan Balmain. Clonal evolution of skin carcinomas during tumor progression and 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 2376.
Analysis of blood-derived circulating microvesicles for microRNA biomarkers of metastatic and nonmetastatic prostate cancer.
Authors: F. C. Hamdy, R. J. Bryant, T. L. Pawlowski, G. Marsden, S. Smith, R. Vessella, C. D. Kuslich
Journal: Journal of Clinical Oncology (2011)

4626 Background: Attempts to find a blood-based biomarker for prostate cancer (PCa) detection have been challenging. Quantification of microRNAs (miRs) in blood may identify potential genetic biomarkers. Using plasma-derived circulating microvesicles (cMV) as an enriched source of miRs from cells, we sought a miR biosignature that could distinguish PCa samples from healthy controls as well as a separate miR biosignature for metastatic PCa. Methods: RNA was isolated from plasma-derived cMV from men with PCa (nonmetastatic and metastatic) and men with negative prostate biopsies. The samples were profiled for 750 miRs by a qRT-PCR panel. miRs with significant differences in expression were validated in larger sample sets using a TaqMan gene expression assay. Results: Ten of 750 miRs compared in nonmetastatic PCa (n=64) and normal control (n=28) samples were found to have a >2.0-fold change with a P value <0.01. In a validation set (N=168), expression of 2 of the 10 miRs, hsa-miR-107 (P=0.03) and hsa-miR-574-3p (P=0.02), were significantly different between the nonmetastatic PCa (n=133) and control (n=35) samples. Comparison of metastatic (n=15) and nonmetastatic (n=55) samples found that 16 out of 750 miRs had a >2.0-fold change with a P value <0.01. Quantitation of these miRs in the subsequent validation set (39 metastatic and 73 nonmetastatic) found 6 of the 7 miRs tested validated (hsa-miR-200b, hsa-miR-375, hsa-miR-141, hsa-mir-331-3p, hsa-miR-181a, and hsa-miR-574-3p). In a separate cohort, hsa-miR-141 and hsa-miR-375 levels were significantly higher in cMV from the serum of metastatic PCa patients (n=47) than in cMV of nonrecurrent PCa patients (n=72; P=0.0001). Conclusions: Blood-derived cMV are a reliable source of miR for biomarkers. There was higher expression of 2 miRs in PCa samples than in controls. In metastatic plasma-derived cMV samples, there was higher expression of 7 miRs, and 2 of these (hsa-miR-141 and hsa-miR-375) were also found to be elevated in metastatic serum-derived cMV. These findings suggest the promise of a blood-based assay that utilizes the miR biosignatures of cMV for the detection of prostate cancer and identification of metastatic cases.