tbuckley/cabot-search huggingface dataset:
Obesity Device Drains Stomach
Authors: Rebecca Voelker
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 1280: The intersection of the PI3K/mTOR and HIPPO pathways: a potential therapeutic target for medulloblastoma
Authors: Jennifer S. Ronecker, Paul Lee, Sudeepta Sridhara, Michael LaBagnara, Raj Murali, Meena Jhanwar-Uniyal
Journal: Cancer Research (2016)

Abstract Medulloblastoma (MB) is the most common malignant pediatric brain tumor; it is genetically defined into 4 subgroups which defines the clinical course of the disease. Despite current treatment modalities such as surgical resection, radiation, and chemotherapy, there are still significant morbidities and adverse side-effects. Recently defined genetic pathways could possibly offer a better management and treatment of patients with MB. The HIPPO signaling pathway has recently been shown to intersect with PI3K and Sonic Hedgehog (SHH) pathways to modulate mechanistic target of rapamycin (mTOR), an important regulator in cell growth and migration. The aim of this study is to elucidate the interaction of Hippo and Akt/mTOR signaling pathways with SHH pathways in MB, and define the potential downstream targets of therapy by using combined inhibitors. In order to achieve our goals, we evaluated the expression of activated AKT/mTOR in MB tumors using immunohistochemistry (IHC), along with the expression of transcriptional co-activators yes-associated protein (YAP), a down-stream effector of the HIPPO pathway. Scratch and chemotactic migration were used to assess the motility of MB cells following treatment with inhibitors of the aforementioned pathways. Cell cycle analysis and proliferation were measured using EdU and MTT techniques, respectively. YAP-SiRNA treatment was used to inhibit HIPPO pathway. MicroRNA-29, which mediates the mTOR pathway by modulating PTEN levels, was investigated. Results demonstrated: 1. A significant number of MBs expressed activated pAKTSer473 and pmTORSer2448, along with YAP, the downstream effector of the HIPPO pathway; 2. Treatment with inhibitors of PI3K/AKT (LY294002) and mTOR (rapamycin), given with EGF, significantly reduced cellular motility; 3. SHH inhibitor cyclopamine given with LY294002 or rapamycin significantly reduced cellular motility; 4. Cell proliferation was suppressed by inhibition of the HIPPO pathway using 3 unique 27mer duplexes of YAP1 siRNA treatments; 5. Combined treatment of cyclopamine with either LY294002 or rapamycin caused maximum suppression of cellular growth. In conclusion, these results demonstrate that the Hippo and PI3K/Akt/mTOR pathways are over-expressed in MB, and that the combined targeting of mTOR/HIPPO pathway with SHH inhibitor may provide alternative strategies for the treatment of MB, and offers a targeted therapy for improved prognosis. Citation Format: Jennifer S. Ronecker, Paul Lee, Sudeepta Sridhara, Michael LaBagnara, Raj Murali, Meena Jhanwar-Uniyal. The intersection of the PI3K/mTOR and HIPPO pathways: a potential therapeutic target for medulloblastoma. [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 1280.
Prognostic utility of the presence of extramural vascular invasion in stage II and III colorectal cancer: Data from the FACS randomised controlled trial.
Authors: Sian Alexandra Pugh, David Mant, Nicholas Mark Jenkins, Alexander H Mirnezami, Adrian C Bateman, Tim Iveson, Bethany Shinkins, John Neil Primrose
Journal: Journal of Clinical Oncology (2016)

3575 Background: Estimates of recurrence after resection of colorectal cancer (CRC) with curative intent form the basis of cancer staging and treatment planning. Adjuvant treatment is recommended in stage III and “high-risk” stage II patients. A key feature commonly used to define patients as “high-risk” is the presence of extramural vascular invasion (EMVI). There is a need to define the prognostic utility of EMVI in an accurately staged prospectively followed-up population managed in the modern era. Methods: Observational analysis of data from the FACS (follow-up after colorectal cancer surgery) trial after 5 years of follow-up. All participants had undergone treatment with curative intent for stage I-III primary CRC, with microscopically clear margins, no evidence of metastases on axial imaging and CEA < 10μg/l following completion of treatment. Data on EMVI were extracted from pathology reports and Cox proportional-hazards regression and Kaplan-Meier curves used to compare survival. Results: EMVI was identified in 21% (150/703) of cases and was associated with a higher risk of recurrence (EMVI +ve 38/150, 25%; EMVI -ve 80/553, 15% p = 0.002) which equated to a hazard ratio of 1.92 (95% CI 1.30-2.82). This effect was seen predominantly in stage III (EMVI +ve 31/88, 35%; EMVI -ve 23/140, 16% p = 0.001; HR 2.43 95%, CI 1.42-4.12) but not in stage II disease (EMVI +ve 7/58, 12%; EMVI -ve 44/275, 16% p = 0.45; HR 0.76 95%CI, 0.34-1.69). Overall survival followed the same pattern as DFS: stage II (HR 0.98, 95%, CI 0.55-1.74 p = 0.94) and stage III (HR 1.98, 95%CI, 1.25-3.13 p = 0.004.) Adjusting for adjuvant chemotherapy did not significantly alter the hazard ratios. Recurrences from EMVI positive CRC were less likely to be surgically resectable (EMVI +ve 8/38, 21%; EMVI -ve 40/80, 50% p = 0.003). Conclusions: Analysis of a cohort that underwent rigorous staging to exclude metastatic disease before trial entry indicates that whilst the presence of EMVI corresponds to a higher risk of recurrence in stage III CRC, this is not seen in stage II disease. This may have implications for decision-making regarding adjuvant therapy and highlights the need for a randomised trial in this setting. Clinical trial information: 41458548.
Abstract 3716: Potent radiation enhancement with VX-984, a selective DNA-PKcs inhibitor for the treatment of NSCLC
Authors: Diane Boucher, Russell Hoover, Yuxin Wang, Yong Gu, David Newsome, Pamella Ford, Cameron Moody, Veronique Damagnez, Reiko Arimoto, Shawn Hillier, Mark Wood, William Markland, Brenda Eustace, Kevin Cottrell, Marina Penney, Brinley Furey, Kirk Tanner, John Maxwell, Paul Charifson
Journal: Cancer Research (2016)

Abstract Ionizing radiation (IR), which is widely used for the treatment of cancer, causes double-strand breaks (DSBs) in DNA. If left unrepaired, these DSBs are lethal to the cell. DNA-dependent protein kinase (DNA-PK) is a key enzyme in the non-homologous end joining (NHEJ) pathway that repairs DSBs caused by IR, or chemotherapeutic agents that cause DSBs such as doxorubicin. The goal of these studies was to characterize the radiation enhancing effects of VX-984, a selective and potent ATP-competitive inhibitor of the catalytic subunit of DNA-PK (DNA-PKcs), with a focus on non-small cell lung cancer (NSCLC) cells and tumor xenografts. VX-984 enhances the cytotoxicity of IR in a panel of cancer cell lines including NSCLC cell lines in vitro with dose enhancement factors (DEF) greater than 3. Notably, VX-984 combined with IR in normal human lung fibroblasts minimally enhanced the cytotoxicity compared to IR alone. Additionally, VX-984 decreased DNA-PKcs autophosphorylation on S2056 both in vitro and in vivo in NSCLC cells and attenuated the decay of the DNA damage markers γH2AX and pKAP1 in response to IR. In NSCLC PDX models VX-984, in combination with IR (2 Gy x 3), caused durable complete responses while IR alone only led to a delay in tumor growth, consistent with delayed DNA damage repair. In these models, the combination of VX-984 and IR was well tolerated. These data demonstrate that VX-984 is a potent radiation-enhancing agent and provide a strong rationale for the use of VX-984 in combination with IR for the treatment of NSCLC. Citation Format: Diane Boucher, Russell Hoover, Yuxin Wang, Yong Gu, David Newsome, Pamella Ford, Cameron Moody, Veronique Damagnez, Reiko Arimoto, Shawn Hillier, Mark Wood, William Markland, Brenda Eustace, Kevin Cottrell, Marina Penney, Brinley Furey, Kirk Tanner, John Maxwell, Paul Charifson. Potent radiation enhancement with VX-984, a selective DNA-PKcs inhibitor for the treatment of NSCLC. [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 3716.
EXPERIENCIA EN LA APLICACIÓN DEL SISTEMA DE SUTURA OVERSTITCH EN PATOLOGÍAS ENDOSCÓPICAMENTE PROBLEMÁTICAS
Authors: F González-Panizo Tamargo
Journal: Endoscopy (2015)

Introducción: APOLLO OVERSTITCH (Apollo Endosurgery. Austin, Texas) es un sistema de sutura para procedimientos NOTES de reciente aparición. Debido a la sencillez, seguridad y eficacia mostrada en este campo, se está evaluando su utilidad como herramienta en la práctica endoscópica habitual para manejar patologías para los que no disponemos de alternativas eficaces actualmente. Los resultados publicados son prometedores. Presentamos nuestra experiencia aplicando este sistema de sutura en situaciones clínicas frecuentes en nuestra unidad.
Mean eccentricity index strongly reflects mPAP in patients with IPAH using CINE cardiac MRI
Authors: Andrew Swift, Smitha Rajaram, Robin Condliffe, Helen Marshall, Dave Capener, Judith Hurdman, Charlie Elliot, David Kiely, Jim Wild
Journal: European Respiratory Journal (2011)

Introduction:  Left ventricular systolic eccentricity index (sEI) measured at echocardiography has been shown to correlate with pulmonary artery pressure in patients with pulmonary hypertension (PH). This study assesses the relationship of sEI, diastolic eccentricity index (dEI) and mean eccentricity index (mEI) with mPAP in patients with idiopathic pulmonary arterial hypertension (IPAH) using CINE cardiac MRI.   Methods:  We studied 36 patients with IPAH who underwent RHC and MRI within 48 hours. MR imaging was performed on a 1.5T whole body scanner GE HDx (GE Healthcare), short axis (SA) cine images were acquired using a cardiac gated multi-slice balanced steady state free precession sequence. Measurements were obtained from the mid-chamber SA end-systolic image and end diastolic images, the ratio D2/D1 was calculated in systole and diastole, where D2 is the diameter parallel and D1 is perpendicular to the IVS. mEI is calculated from (sEI +dEI)/2. A second observer (SR) repeated the measurements.   Results:  The correlation between mEI and mPAP was highly significant at r=0.95, p  A good level of interobserver agreement was demonstrated for our eccentricity index measurements, k=0.80.   Discussion:  A strong relationship between mEI and mPAP has been demonstrated in our cohort of patients with IPAH.
P1026 : The evaluation of non-alcoholic fatty liver disease (NAFLD) and its associate factors in psoriasis patients using ultrasonography and the controlled attenuation parameter (CAP) measured with transient elastography
Authors: A. Sobhonslidsuk, J. Pongpit, A. Thakkinstian, S. Porntharukchareon, P. Kaewdoung, K. Promson, W. Stitchantrakul, D. Saengwimol, S. Petraksa, N. Rajatanavin
Journal: Journal of Hepatology (2015)
SPARC microenvironment signature (SMS) in patients treated with nab-paclitaxel (nabP)/carboplatin (C)/bevacizumab(B) for triple-negative metastatic breast cancer (TNMBC).
Authors: K. L. Blackwell, E. P. Hamilton, G. Rocha, M. Gainey, V. N. Trieu, K. Motamed, P. Pramanik, L. Hwang, T. Treece, N. Desai
Journal: Journal of Clinical Oncology (2010)

e21040 Background: SPARC is an albumin-binding protein associated with poor prognosis that may mediate intratumoral accumulation of nab-P. SPARC is associated with both tumor cells and stromal components. We examined SMS in paired primary (P) and metastatic (M) TNBC biopsies (bxs) to 1) determine changes in expression, and 2) examine potential correlations with response to therapy with nab-P/C/B. Methods: First- and second-line TNMBC pts (n = 27) received nabP (100 mg/m2) and C (AUC = 2) on d1,8,15 of a 28 d cycle. B (10 mg/kg) was given on d1, 15. Paraffin- embedded P and M bxs were required (first line). PFS, ORR, and CBR were determined. Tumor SMS was determined using a validated SPARC IHC method. Scoring included: % cells stained in each field, intensity of staining, and overall score. Multivariable IHC data were analyzed using GeneSpring and Nexus analysis programs. Results: SMS data were available for 20 pts. SMS of M bx distinguished a low risk (n= 5, PFS = 16.0 mos) from a high risk group (n = 15, PFS = 4.9 mos), p = 0.03. SMS of P bx did not correlate with outcome. Of 17 first-line paired P and M bx (from 15 pts), 8 M SPARC signatures were similar to the P (p < 0.05) and 9 were dissimilar (p ≥ 0.05). For the dissimilar group, 3 microenvironment variables were higher in the M bx compared to P bx: % Blood vessel, % Inflammatory cells, and % Fibroblasts, p = 0.006, 0.06, and 0.06. In 14 pts with paired bx and ORR data, M bx that were similar to their P had better response than those with dissimilar M bx: CR 3/7 (43%), PR 4/7 (57%), and SD 0/7 (0%)vs CR 0/7 (0%), PR 5/7 (71%), and SD 2/7 (29%), p = 0.03. PFS for similar and dissimilar pairs was not different. Conclusions: In this small sample of TNMBC, the SMS of M bxs discriminated tumors with a short PFS from those with a longer PFS. Archival P bx SMS did not correlate with outcomes and M SMS were significantly different from the corresponding P SMS in over half of the pts. The change in the SMS from the P to M tumors was associated with reduced response to nab-P/C/B chemotherapy. SMS should be explored further in both primary and metastatic tumors in order to further define it prognostic and predictive significance. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience Abraxis BioScience Abraxis BioScience
Early “Mini” Donor Lymphocyte Infusions after Reduced-Intensity Conditioning in Allogeneic Transplant of Highly Purified CD34+ Cells from HLA-Identical Donors in Pediatric Leukemia Patients.
Authors: Miguel A. Diaz, Marta Gonzalez-Vicent, Manuel Ramirez, Antonio Perez, Javier Garcia-Castro, Julian Sevila, Luis Madero
Journal: Blood (2005)
Prospective Evaluation of MRI and PET-CT at Diagnosis and before Maintenance Therapy in Symptomatic Patients with Multiple Myeloma Included in the IFM/DFCI 2009 Trial
Authors: Philippe Moreau, Michel Attal, Lionel Karlin, Laurent Garderet, Thierry Facon, Lotfi Benboubker, Margaret Macro, Denis Caillot, Martine Escoffre-Barbe, Anne-Marie Stoppa, Kamel Laribi, Cyrille Hulin, Gerald Marit, Jean-Richard Eveillard, Florence Caillon, Caroline bodet-Millin, jean-Michel Nguyen, Brigitte Pegourie, Veronique Dorvaux, Carine Chaleteix, Benoit Dupas, Françoise Bodere
Journal: Blood (2014)
Vascular Dysfunction an Early Contributor to Alzheimer Disease
Authors: Tracy Hampton
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 2933: Long-term BRAF(V600E) inhibition results in a spontaneous KRAS(G12D) mutation and increased epithelial to mesenchymal transition (EMT) in papillary thyroid cancer cells (PTC)
Authors: Brian P. Danysh, Maria E. Cabanillas, Marie-Claude Hofmann
Journal: Cancer Research (2016)

Abstract Objective: Activating mutations in BRAF(V600E) are commonly observed in PTC and result in a functional dependence upon the constitutively active MAPK pathway. While targeted inhibitors are initially effective, inevitably cells develop alternative mechanisms of pathway activation. Mechanisms of primary resistance have been described in thyroid cancer cell lines, however acquired resistance has not. Our study investigates adaptive mechanisms of BRAF(V600E) inhibitor resistance and accompanying metastatic phenotypes in PTC cells following long-term vemurafenib exposure. Materials &amp; Methods: KTC1 sub-cell lines (PTC cells, BRAFV600E) were developed following treatment with either 0.25 or 1.0 μM of vemurafenib, a BRAF V600E inhibitor, for &amp;gt;20 passages. Western blot and qRT-PCR were used to assess EMT marker expression and pathway activation. 2D and 3D invasion assays, immunofluorescence microscopy, and direct cell count growth assays were used to assess inhibitor resistance and metastatic phenotypes. Sequenom was used to detect acquired mutations. Results: A vemurafenib resistant (VR) subline of KTC1 cells was derived following long-term treatment with the drug. Resistance coincided with spontaneous acquisition of a KRAS(G12D) activating mutation. Our data show KRAS(G12D) driven vemurafenib-resistance significantly enhanced expression of distinct EMT markers and translated into increased growth, migration, and invasion, when compared to the control sub-lines. This gain in metastatic phenotype coincided with increase activation of both the AKT and ERK pathways. Conclusion: Our results suggest an acquired KRAS mutation confers BRAF V600E inhibitor resistance and a more aggressive metastatic phenotype in vitro. Our hope is that further study of the mechanisms of resistance will add to potential markers for early detection of BRAF inhibitor resistance, leading to improved patient outcomes. Citation Format: Brian P. Danysh, Maria E. Cabanillas, Marie-Claude Hofmann. Long-term BRAF(V600E) inhibition results in a spontaneous KRAS(G12D) mutation and increased epithelial to mesenchymal transition (EMT) in papillary thyroid cancer cells (PTC). [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 2933.
Abstract 2811: Antioxidant compounds and their effects on ECM-detached ovarian cancer cells
Authors: Calli A. Davison-Versagli
Journal: Cancer Research (2016)

Abstract Epithelial ovarian cancer (EOC) has the highest mortality rate of all gynecological cancers. Approximately 70% of all EOC patients are diagnosed at advanced stages of the disease. In these patients, ovarian cancer cells shed from the primary tumor and accumulate in ascites in the peritoneal cavity. These shed cells have shown the ability to attach and form secondary tumors throughout the peritoneal cavity, making EOC more difficult to treat. A better understanding of the molecular mechanisms involved in the survival of ovarian cancer cells in ascites could lead to the development of improved chemotherapeutics aimed at eradicating this nonadhesive subset of cells and thus resulting in better survival rates of EOC patients. While non-tumorigenic epithelial cells require attachment to the extracellular matrix (ECM) for survival, ovarian cancer cells surviving in ascites gain the ability to survive in anchorage independence. Striking increases of reactive oxygen species (ROS) mediated by ECM-detachment has been shown to inhibit energy production and inhibit cell viability in non-tumorigenic mammary epithelial cells. Consequently, neutralization of ROS with antioxidant compounds enhance ATP production and promote survival in anchorage independence. Furthermore, previous publications from our laboratory suggest that antioxidant enzymes are critical for metabolic maintenance and survival of ECM-detached breast cancer cells. While these recent studies reveal a novel role for antioxidant activity in metastatic breast cancer, antioxidant activity and its effects on ECM-detached ovarian cancer cells has yet to be unveiled. Currently, we have found that neutralization of ROS through treatment with a variety of antioxidant compounds increases metabolic efficacy in ECM-detached ovarian cancer cells. More specifically, ECM-detached SKOV3 ovarian cancer cells treated with antioxidant compounds Trolox (a vitamin E analog), Vitamin C, and Epigallocatechin gallate (EGCG) results in large increases in ATP levels. Given these data, we are further working to understand the mechanisms involved in this metabolic increase. In addition, we are working to understand the relationship between this increase in metabolism and survival in anchorage independence. Future studies include looking at this phenomenon in other ovarian cancer cell lines as well as using mouse xenograft studies to examine the effects of antioxidant compounds on survival of metastatic ovarian cancer cells. Citation Format: Calli A. Davison-Versagli. Antioxidant compounds and their effects on ECM-detached ovarian cancer 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 2811.