tbuckley/cabot-search huggingface dataset:
Abstract 3267: Mammalian target of rapamycin (mTOR) signaling proteins are highly expressed in mamamry tumors of MMTV-TGF-β mice
Authors: Soner Dogan, Margot P. Cleary
Journal: Cancer Research (2012)

Abstract Although the roles of many signaling pathways have been investigated to determine their potential role mammary tumor (MT) development the exact molecular mechanisms of mammary tumorigenesis are still not clear. One pathway of interest with respect to cancer development is mTOR signaling which is implicated in cell growth, transcription, translation, migration, differentiation, and survival. In the present study the expression levels of proteins associated with mTOR signaling pathway in MTs and in normal mammary tissues and fat pads were determined in MMTV-TGF-β transgenic mice that develop hormone responsive MTs as they age. Mice were enrolled at 10 wks of age and were ad-libitum-fed AIN-93M diet until 73/74 wks of age. At this time MTs were removed as well as mammary tissue samples from the same location where MT initially grow. Samples were analyzed histopathologically to confirm either MT or normal mammary tissue and mice assigned to MT-positive or MT-negative groups (n=6-8 per group). Protein expression levels were then determined in MT, mammary tissue and as well as mammary fat pads (MFP). Serum insulin, IL-6 and TNF-α levels were also measured. MT- positive mice had 40% higher serum insulin level compared to MT- negative mice. In addition, serum IL-6 levels were 100% higher in MT- positive compared to the MT-negative group. Serum TNFα levels were similar in both groups. Expression levels of mTOR, p70S6K, p4EBP1, and HIF-1 proteins were significantly higher in MT of the MT-positive group compared to the corresponding tissue of MT-negative group, 64%, 106%, 129%, and 43%, respectively. On the other hand, IGF-I receptor (IGF-IR) expression level was significantly lower by 43% in the MT- positive group compared to the MT-negative group. The expression levels of p70S6K, p4EBP1, and HIF-1 proteins were similar in MFP tissues in both groups while mTOR level was lower in MFP taken from MT-positive compared to MT-negative mice. But, IGF-IR level was significantly higher, 187%, in MFP taken from the MT-positive group compared to the MT-negative group. These findings demonstrate that expression levels of the proteins involve in mTOR signaling pathway are higher in MTs compared to normal mammary tissue obtained from the site of MT origin. This supports the potential role of mTOR signaling proteins in breast cancer development and provides targets for cancer prevention. (Support CA101858, The Breast Cancer Research Foundation and The Hormel Foundation). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3267. doi:1538-7445.AM2012-3267
Interleukin-35 Suppresses Allergen-specific Th2 Response in Patients with Grass pollen induced Seasonal Allergic Rhinitis
Authors: D. Achkova, F.W. Chung, J.A. Leyhadi, G.W. Scadding, J. Charlesworth, D. Phippard, S. Durham, M.H. Shamji
Journal: Journal of Allergy and Clinical Immunology (2012)
P666 PREDICTORS OF SEVERE HEPATIC FIBROSIS IN TREATMENT-NAIVE GENOTYPE B OR C INFECTED E ANTIGEN-POSITIVE AND -NEGATIVE CHRONIC HEPATITIS B PATIENTS
Authors: W.-P. Su, C.-Y. Peng, H.-C. Lai, C.-H. Lin, P.-H. Chuang, S.-H. Chen
Journal: Journal of Hepatology (2014)
Abstract 5413: Role of NANOG in modulating cancer cell metabolism.
Authors: Lifeng Yang, Hongyun Zhao, Juan C. Marini, Collene Jeter, Dean Tang, Deepak Nagrath
Journal: Cancer Research (2013)

Abstract Tumors and cancer cell lines are both heterogeneous populations and contain a sub-population of undifferentiated cells known as cancer stem cells (CSCs) that are able to renew, proliferate and differentiate into tumor cells. Recent studies have shown that transcription factors (TFs) that are implicated in the pluripotency maintenance of embryonic stem cells (ESCs) are over-expressed in many tumors. Origin and progression of cancer is the result of a complex network of communication between tumor initiating cells also known as cancer stem cells (CSCs) and epithelial cells. Despite the knowledge about involvement of NANOG in modulation of cancer progression, oncogenic signaling, and tumorigenesis, it is not known about how NANOG regulates metabolic fluxes and alter cancer cell's metabolism. Here, we show that NANOG can shift cancer cells metabolism from oxidative phosphorylation to glycolysis, to meet cancer cell's energy needs, redox balance, proliferation, and invasion. Our findings are based on the quantification of metabolites, related to glycolysis, the pentose phosphate pathway, the TCA and urea cycles, and amino acids and nucleotide metabolism, and comparison of these pathways fluxes under induced and uninduced NANOG expression. Our results demonstrate the metabolic targets of NANOG on cancer progression. These insights will present a unique opportunity for diagnosing and treating cancer through CSCs. Citation Format: Lifeng Yang, Hongyun Zhao, Juan C. Marini, Collene Jeter, Dean Tang, Deepak Nagrath. Role of NANOG in modulating cancer cell metabolism. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5413. doi:10.1158/1538-7445.AM2013-5413
A randomized phase II design with a time-to-event endpoint using predictive probability of success of the follow-up phase III study as the criteria for go/no-go decision.
Authors: B. Chen, X. Fan, Y. Wang, S. Jauffret, J. Dey, R. Waltzman, E. M. Lopez-Martin, K. Malek, S. Kreitz, E. Zuber
Journal: Journal of Clinical Oncology (2010)

e18078 Background: The goal of a phase II study is to gather information to assess the efficacy and safety of an investigational product and make decisions on future development. A necessity is to conduct such studies much faster and with smaller sample size than a typical phase III study. As a result, the study outcome is often assessed based on a surrogate endpoint like response rate, with a remote interpretation regarding the probability of success in future development. We present here the design of a randomized phase II study with a time-to-event endpoint using the predictive probability of success (PPS) of a follow-up phase III study as the criteria to determine whether to continue the development of a new agent or regimen. The interpretation of success in phase III is achieving a statistically significant result (p ≤0.05) of the planned confirmatory study in the same patient population with the same endpoint given the information obtained in the phase II study. Methods: The proposed design using a Bayesian framework is implemented in a randomized, placebo-controlled phase II study comparing a new agent in combination with a standard regimen with the standard regimen alone. The subsequent phase III study is to observe 508 deaths for a 90% power to detect a survival hazard ratio (HR) of 0.75 at a 5% 2-sided alpha level. It is planned to accrue 160 patients into the phase II with analyses performed when 90 and 120 events are observed. Results: None. Conclusions: This design provides a readily interpretable quantification of the chance of observing a positive efficacy outcome in a subsequent future phase III with a novel agent or regimen based on phase II study results. PPS for various combinations of HRs observed in the phase II study Observed HR Observed number of events 90 120 0.70 0.780 0.810 0.75 0.682 0.706 0.80 0.578 0.589 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis, sanofi-aventis
EPID-05EPIDEMIOLOGY OF BRAIN AND CENTRAL NERVOUS SYSTEM TUMORS IN ADOLESCENTS AND YOUNG ADULTS IN THE UNITED STATES
Authors: Quinn Ostrom, Carol Kruchko, Jill Barnholtz-Sloan
Journal: Neuro-Oncology (2015)

BACKGROUND: Brain and central nervous system (CNS) tumors in adolescents and young adults (AYA) are a distinct group of tumors that pose challenges to treatment and reporting.Cancer that occurs in this age group is biologically distinct from those in other age groups and poses significant challenges for clinicians.While cancer survival has been improving overall, AYA have not experienced these same increases and in some cases may have worse survival than those over 40 years.METHODS: Using data from 51 central cancer registries from 2007-2011, we calculated the average annual age-adjusted incidence rates (AAIR) per 100,000 population of brain and CNS tumors in AYA by histologic type.We also calculate the relative survival after diagnosis using data from 18 SEER registries from 1995-2011.RESULTS: Approximately 15% of all brain and CNS tumors occur in the AYA age group, 51,118 total tumors from 2007-2011.The most common histologies are tumors of the pituitary (AAIR: 2.90), meningioma (AAIR: 1.68), and nerve sheath tumors (AAIR: 0.88).Gliomas account for 29% of all tumors.AYA have higher rates of relative survival than adults 40+ for all histologic types.One-year relative survival for most tumor types is higher for AYA than children ,15 years old, but 10-year survival is usually higher for children as compared to AYA.CONCLUSION: Brain tumors are a significant source of cancer-related morbidity and mortality in adolescents and young adults.This age group is diagnosed with unique groups of cancers that require separate reporting in order to accurately portray their impact in these populations.
Abstract 1250: Crosstalk between Notch and MAPK signaling regulates proliferation in papillary thyroid cancer
Authors: Alex S. Yamashita, Murilo V. Geraldo, Edna T. Kimura
Journal: Cancer Research (2012)

Abstract Background: RET/PTC, RAS and BRAF are present in about two thirds of papillary thyroid carcinomas (PTC), activating constitutively the mitogen activated protein kinase (MAPK) signaling pathway. There is practically no overlap between RET/PTC, RAS and BRAF mutations in PTC, the lack of concordance for these mutations provides compelling genetic evidence for the requirement of this signaling system for transformation to PTC. However, the effect of these genetic alterations in other signaling pathways remains unclear, which could, at least in part, cooperates in transformation. Recently, Notch signaling has been implicated in tumorigenesis in other cancer types. In this study, we test the hypothesis that RET/PTC and BRAFT1799A oncogenes crosstalks and regulates Notch pathway. Methods: TPC-1 and BCPAP (human PTC cells harboring RET/PTC1 rearrangement and BRAFT1799A mutation, respectively) were treated with gamma secretase inhibitor (GSI) and proliferation was analyzed by MTT assay and growth curve; cell cycle and apoptosis were analyzed by flow cytometry. PCCL3 cells harboring Doxycycline-inducible RET/PTC3 and BRAFT1799A (PC-BRAF) were used to analyze protein and gene expression by Western blotting and real-time PCR, respectively. Notch1 protein expression was analyzed in transgenic mice (Tg-BRAF) which harbor targeted expression of BRAFT1799A restricted to thyroid gland. Results: PTC cells treated with GSI decreased the percentage of viable cell in a dose-dependent manner and reduced the growth rate. Cell cycle analysis in PTC cells showed enhancement of DNA fragmentation and increased apoptotic cells. Furthermore, the GSI treatment in PTC cells modulates cell cycle related genes, increasing CDKN1A and CDKN1B gene expression and reducing CCND1, MCM6, CKS2, and MADL2 expression. Conditional activation of RET/PTC3 and BRAFT1799A in PTC3-5 and PC-BRAF cells, respectively, showed a sustained enhancement in pERK protein expression, increased Notch1 protein and gene expression and Hes1 gene expression, the target gene of Notch signaling. Furthermore, transgenic mice Tg-BRAF showed a stronger stain for Notch1 in follicular and stromal cells. Treating PTC cells with MEK inhibitors, U0126 or PD96059, reduces NOTCH1 and HES1 gene expression. The combination of GSI with MEK inhibitor enhances the growth suppression promote by MAPK signaling inhibition in PTC cell proliferation. CONCLUSION: Taken together, targeting Notch signaling resulted in anti-proliferative effect, suggesting an important role of Notch signaling in tumorigenesis of MAPK-induced PTC and our results indentify Notch signaling as a potential therapeutic target in thyroid cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1250. doi:1538-7445.AM2012-1250
Hirschsprung's Disease: A New Concept of the Etiology
Authors: Orvar Swenson, Harold F. Rheinlander, Israel Diamond
Journal: New England Journal of Medicine (1949)

CONGENITAL megacolon has been recognized as a clinical entity for over a hundred years. Many reports were written on the subject before Hirschsprung1 published his classic description of the disease in 1888. His presentation included the clinical study and autopsy findings of 2 patients with megacolon and was more complete than anything previously recorded. Subsequently, scores of papers have been written on the etiology and treatment of megacolon.The numerous theories set forth in these publications may be divided into four categories and summarized as follows2 , 3:The disease is due to congenital lesions in the dilated colon. Hirschsprung1 thought . . .
860 IMMUNOSTAINING AND 3D ANALYSES OF CORE AND NS5A HCV ANTIGENS IN LIVER BIOPSIES OF PATIENTS WITH HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANTATION
Authors: L. Mensa, S. Perez del Pulgar, G. Crespo, G. Koutsoudakis, C. Fernandez, R. Miquel, X. Forns
Journal: Journal of Hepatology (2012)
Expression of Phosphorylated Proteins from PI3-Kinase and MAP-Kinase Signaling Pathways in Infiltrating Breast Cancer: Relation with Histopathologic and Molecular Subtypes
Authors: J. Merlin, A. Harle, M. Lion, A. Chretien, C. Ramacci, A. Leroux
Journal: Annals of Oncology (2013)
EMPLEO DE PROTESIS METALICAS EXPANDIBLES EN LA NEOPLASIA COLORRECTAL PRIMARIA
Authors: E Sánchez Hdez, I Castro Novo, P Vega Villamil, A Dacal Rivas, P Quintas Lorenzo, R Macenlle García, V García-Luengos, J Fernández Seara
Journal: Endoscopy (2010)

Introducción y objetivo: El empleo de prótesis autoexpandibles han modificado el manejo de los pacientes con neoplasia colorrectal en los últimos años, sobre todo en situaciones paliativas y como puente previo a la cirugía. Analizamos los resultados de los casos en nuestro centro con un único modelo de prótesis metálica expandible enteral.
THE ROLE OF FDG-PET IMAGING IN DETECTING EARLY RESPONSE TO CHEMOEMBOLIZATION IN HEPATIC COLORECTAL CARCINOMA METASTASES
Authors: R. L. Korn, B. W. Zuckerberg, R. Smith, M. Soulen, L. Shao, A. Alavi
Journal: Clinical Nuclear Medicine (1996)

Korn, R. L.; Zuckerberg, B. W.; Smith, R.; Soulen, M.; Shao, L.; Alavi, A.Editor(s): Blend, Michael; Haseman, Michael Author Information
Abstract 938: Discovery of Dendrogenin A as the first endogenous alkylaminooxysterol present in mammals with potent cell differentiation and anticancer activity
Authors: Marc Poirot, Philippe de Medina, Michael R. Paillasse, Grégory Segala, Tallal Al Saati, Sandrine Silvente-Poirot
Journal: Cancer Research (2011)

Abstract We recently reported that anti-tumor and chemopreventive drugs such as tamoxifen, raloxifene and docasahexaenoic acid are inhibitors at therapeutic doses of cholesterol epoxide hydrolase (ChEH), the enzyme that transforms cholesterol-5,6-epoxides (CE) into cholestane-3β,5α,6β-triol (CT) (de Medina et al, PNAS, 2010). Several lines of evidence point to the existence of an active metabolism centered on CE. We recently reported that the aminolysis of α-CE by biogenic amines under catalytic conditions generated powerful cell differentiating alkylaminooxysterols (de Medina et al, J Med Chem, 2009). Among these active molecules, Dendrogenin A (DDA) was synthesized, based on the hypothesis that it could be an endogenous metabolite formed by the reaction of α-CE with histamine at the level of the ChEH. In the present study, we report the existence of DDA in mammals at concentrations ranging from 70 to 500 pmol/g in tissues and at concentrations 70 to 500 times less in the circulation, while only trace levels of AF17, the regio-isomer of DDA, were detected. DDA was not found in a panel of cancer cells, suggesting a possible deregulation of its synthesis during oncogenesis. In addition, we showed that DDA is the most potent natural inhibitor of ChEH with an IC50 around 100 nM and it exhibits tumor differentiation and anti-tumor activity in cell and animal models. In vivo, these effects were associated with a T cell-mediated anti-tumor response. AF17 was found to be inactive in these different tests, showing a regio-selectivity of action of these compounds. In conclusion, our results shed light on a new metabolic pathway that generates the first endogenous steroidal alkaloid ever described in mammals that may have important functions in maintaining cell integrity and differentiation as well as immune system alert. The discovery of DDA reveals an unexpected cross-talk between cholesterol and histamine metabolism. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 938. doi:10.1158/1538-7445.AM2011-938
Study Suggests Transfusions May Increase Cancer Risk
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Study Suggests Transfusions May Increase Cancer Risk Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 4, 16 February 1994, Page 260, https://doi.org/10.1093/jnci/86.4.260 Published: 16 February 1994
AB0276 The MRI Features in Patients with Rheumatoid Arthritis RA in Clinical Remission or Low Disease Activity
Authors: N. Bensaoud, S. Rostom, R. Bahiri, B. Amine, F. Allali, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To evaluate in patients with RA in clinical remission or low disease activity (LDA),the synovitis and the osteitis using MRI by OMERACT RAMRIS score (RAMRIS bone edema and synovitis RAMRIS). <h3>Methods</h3> In this longitudinal study, were included patients with rheumatoid arthritis RA according to the American College of Rheumatology ACR 1987 criteria with inadequate response or intolerance to DMARDs, treated with tocilizumab (TCZ).Sociodemographic characteristics, clinical and laboratory for the disease were collected at baseline (M0) and 06 months (M6) of treatment. Clinical remission was defined by a DAS28-CRP &lt;2.6. The low disease activity (LDA) was defined by DAS28-CRP ≤2.6 &lt;3.2. All patients underwent MRI of the dominant hand and wrist. MRI features were evaluated according to the Outcome Measure Clinical Trial in Rheumatoid Arthritis Rheumatoid Arthritis MRI Scoring system (OMERACT RAMRIS synovitis and bone oedema). <h3>Results</h3> 22 patients with RA were included, 19 females (86.4%),with a mean of age 42±13.7. The mean disease duration was 8±5.2 years.The mean DAS28 was 5.8±0.94. Three patients were excluded from the study for serious side effects. At 06 months, 13 patients (52%) were in clinical remission, 04 patients (16%) in LDA, and 04 patients (16%) had active disease. The mean SDAI was 21.5±19.7.The mean CDAI was 16±19.6.The mean RAMRIS score was 2.23±6.33 for bone oedema, 4.76±4.02 for synovitis and 43.32±30 for erosion.Using DAS28CRP as criteria of remission, it did not exist significant differences between the 3 groups of patients (remission/LDA/active disease) for the presence of synovitis on MRI (p=0.67), and their severity (RAMRIS synovitis p=0.50). There was also no difference between the three groups for the presence of bone oedema (p=0.55), and their severity by RAMRIS bone oedema (p=0.55). Moreover, defining remission by SDAI and CDAI, the RAMRIS synovitis and bone oedema RAMRIS did not differ by the level of disease activity. Thus synovitis and oedema bone are not frequent in patients in clinical remission (synovitis/osteitis: 69%/75%) versus (15.4%/25%) LDA. <h3>Conclusions</h3> This study suggests that patients in clinical remission or LDA evaluated by DAS28CRP showed no inflammation (synovitis and bone edema) on MRI. Although MRI and ultrasound are currently one of the criteria for remission in RA, further studies are needed in particular to determine the threshold definition of remission on MRI <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5959
The Paradoxical Problem with Multiple-IRB Review
Authors: Jerry Menikoff
Journal: New England Journal of Medicine (2010)

The federal system for protecting research subjects was designed decades ago, when most research studies took place at a single institution. These days, if a study is conducted at multiple sites, an ethics review by an institutional review board (IRB) may be repeated many times. This practice has been criticized for both wasting resources and leading to inappropriate delays in the conduct of research.1 One might suppose that this resource-intensive effort at least substantially improves the ethical integrity of multisite studies. In fact, however, there is reason to believe that not only do these duplicative reviews provide relatively few benefits, . . .