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119 results on '"Shapiro, G.I."'

3. Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer

Author

Waks, A.G., Cohen, O., Kochupurakkal, B., Kim, D., Dunn, C.E., Buendia Buendia, J., Wander, S., Helvie, K., Lloyd, M.R., Marini, L., Hughes, M.E., Freeman, S.S., Ivy, S.P., Geradts, J., Isakoff, S., LoRusso, P., Adalsteinsson, V.A., Tolaney, S.M., Matulonis, U., Krop, I.E., D’Andrea, A.D., Winer, E.P., Lin, N.U., Shapiro, G.I., and Wagle, N.

Published
2020
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5. Phase I study of the checkpoint kinase 1 inhibitor GDC-0575 in combination with gemcitabine in patients with refractory solid tumors

Author

Italiano, A., Infante, J.R., Shapiro, G.I., Moore, K.N., LoRusso, P.M., Hamilton, E., Cousin, S., Toulmonde, M., Postel-Vinay, S., Tolaney, S., Blackwood, E.M., Mahrus, S., Peale, F.V., Lu, X., Moein, A., Epler, J., DuPree, K., Tagen, M., Murray, E.R., Schutzman, J.L., Lauchle, J.O., Hollebecque, A., and Soria, J.-C.

Published
2018
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12. Formation of a dense water cascade in the marginal ice zone in the Barents Sea

Author

Ivanov, V.V. and Shapiro, G.I.

Subjects
Ice -- Analysis, Environmental sciences -- Analysis, Oceanography -- Analysis, Density currents -- Analysis, Salinity -- Analysis, Earth sciences
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.dsr.2005.04.004 Byline: V.V. Ivanov (a), G.I. Shapiro (b)(c) Keywords: Dense water formation; Shelf edge dynamics; Overflow; Ice transport; Oceanic fronts; Arctic Ocean Abstract: In this paper, we examine the origin of a dense water cascade in the marginal ice zone west off the Novaya Zemlya Archipelago in the Barents Sea. We specifically consider how ice advection and melting contribute to the formation of density gradients favourable for cascading. The study is based on three hydrographic surveys taken in December 1987 by Russian research vessels, composite ice maps and meteorological records. A bulk numerical model is applied in order to quantify the dominant physical processes responsible for re-shaping the thermohaline structure, from a state that opposes cascading to one that enhances it. The overall effect of these processes significantly varies depending on the distance from the shore. The most intensive ice production and rapid density increase occurred in the shallow waters, where the salinity increase accounted for almost 90% of the total density increase. The transitional zone, covering the outer shelf and slope waters, is subject to strong freshening by melting ice, which is transported from the production zone. This effect diminishes in the deep water, where the amount of imported ice is small. The opposing trends in salinity in the production and transitional zones caused by the joint effects of freezing/melting and ice mobility play a crucial role in providing the necessary conditions for the onset of cascading. Without ice advection and melting, the density contrast between the shallow and deeper waters at the shelf break would have been -0.10 (kg/m.sup.3), which would inhibit the formation of dense water cascade. The difference in density fluxes on both sides of the front was 2.1x10.sup.-5 (kg/m.sup.2 s), which is comparable with average flux over Arctic polynyas, and resulted in a cross-frontal density difference of 0.06kg/m.sup.3, which favours dense water cascading. Author Affiliation: (a) International Arctic Research Center, University of Alaska, Fairbanks, AL 99775, USA (b) School of Earth, Ocean and Environmental Sciences, University of Plymouth, UK (c) Shirshov Institute of Oceanology, Moscow, Russia Article History: Received 10 November 2003; Revised 14 February 2005; Accepted 19 April 2005

Published
2005

15. Randomized phase II (RP2) study of ATR inhibitor M6620 in combination with gemcitabine versus gemcitabine alone in platinum-resistant high grade serous ovarian cancer (HGSOC)

Author

Konstantinopoulos, P.A., primary, Wahner Hendrickson, A.E., additional, Penson, R.T., additional, Doyle, A., additional, Kohn, E.C., additional, Duska, L.R., additional, Crispens, M.A., additional, Olawaiye, A.B., additional, Winer, I.S., additional, Barroilhet, L.M., additional, Fu, S., additional, McHale, M.T., additional, Schilder, R.J., additional, Farkkila, A., additional, Curtis, J., additional, Quinn, R., additional, Whalen, C., additional, Shapiro, G.I., additional, and Matulonis, U.A., additional

Published
2019
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16. A phase I open label dose escalation trial evaluating VT1021 in patients with advanced solid tumours

Author

Harb, W., primary, Patnaik, A., additional, Mahalingam, D., additional, Liu, J., additional, Wen, P.Y., additional, Shapiro, G.I., additional, Bullock, A.J., additional, Juric, D., additional, Zheng, L., additional, Moore, K., additional, Patel, M., additional, Guttendorf, R., additional, Wang, S., additional, Kerstein, K., additional, Berk, G., additional, Cieslewicz, M.J., additional, and Watnick, J., additional

Published
2019
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17. A phase IIa clinical trial combining ALRN-6924 and palbociclib for the treatment of patients with tumours harboring wild-type p53 and MDM2 amplification or MDM2/CDK4 co-amplification

Author

Meric-Bernstam, F., primary, Somaiah, N., additional, DuBois, S.G., additional, Dumbrava, E E Ileana, additional, Shapiro, G.I., additional, Patel, M.R., additional, Goel, S., additional, Bauer, T., additional, Pinchasik, D., additional, Annis, A., additional, Aivado, M., additional, Vukovic, V., additional, and Saleh, M., additional

Published
2019
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18. Phase I/II study of combined BCL-XL and MEK inhibition with navitoclax (N) and trametinib (T) in KRAS or NRAS mutant advanced solid tumours

Author

Corcoran, R.B., primary, Do, K.T., additional, Cleary, J.M., additional, Parikh, A.R., additional, Yeku, O.O., additional, Weekes, C.D., additional, Veneris, J., additional, Ahronian, L.G., additional, Mauri, G., additional, Van Seventer, E.E., additional, Fetter, I.J., additional, Gurski, J.M., additional, Matulonis, U.A., additional, Juric, D., additional, Flaherty, K.T., additional, Sullivan, R.J., additional, Clark, J.W., additional, Heist, R.S., additional, and Shapiro, G.I., additional

Published
2019
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19. The Malin cascade in winter 1996

Author

Hill, A.E., Souza, A.J., Jones, K., Simpson, J.H., Shapiro, G.I., McCandliss, R., Wilson, H., and Leftley, J.

Subjects
Ireland -- Natural history, Cascades (Fluid dynamics) -- Research, Climatology -- Research, Salinity -- Research, Biological sciences, Earth sciences
Abstract

A study was conducted to analyze the cascading of shelf-edge water along the continental slope northwest of Ireland at 55N in Feb 1996. Results indicated a downslope penetration of the cascade that can be determined using the measured excess density of shelf-edge waters supporting a realistic level of entrainment of overlying slope waters. Findings also correlated the cascade with relatively higher shelf-edge salinities supporting buoyancy deficit.

Published
1998

20. A young lens of Red Sea Water in the Arabian Sea

Author

Meschanov, S.L. and Shapiro, G.I.

Subjects
Arabian Sea -- Research, Oceanographic research -- Analysis, Salinity -- Research, Earth sciences
Abstract

The structure and dynamics of a young lens of Red Sea Water was examined using CTD data gathered by RV Akademik Bernadsky during its 22nd cruise in Mar-Apr 1980. Analysis of the data shows that the center of the young lens, which has a maximum temperature of 11.07 degrees celsius and maximum salinity of 35.56, was found at depths of 640-830 m and carried temperature and salinity anomalies of 0.75 degrees celsius and 0.22, respectively. It was also observed that the density anomaly of Red Sea Water's young lens is limited up to 0.04 kgm(super -3)

Published
1998

24. Neratinib in patients with HER2-mutant, metastatic cervical cancer: findings from the phase 2 SUMMIT ‘basket’ trial

Author

D’Souza, A., primary, Roman, L.D., additional, Saura, C., additional, Braña, I., additional, Shapiro, G.I., additional, Passalacqua, R., additional, Piha-Paul, S., additional, Cutler, R.E., additional, Shahin, S., additional, Eli, L.D., additional, Xu, F., additional, Dujka, M., additional, Lalani, A.S., additional, Bryce, R., additional, Meric-Bernstam, F., additional, Solit, D.B., additional, and Hyman, D.M., additional

Published
2019
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27. LBA60 - Randomized phase II (RP2) study of ATR inhibitor M6620 in combination with gemcitabine versus gemcitabine alone in platinum-resistant high grade serous ovarian cancer (HGSOC)

Author

Konstantinopoulos, P.A., Wahner Hendrickson, A.E., Penson, R.T., Doyle, A., Kohn, E.C., Duska, L.R., Crispens, M.A., Olawaiye, A.B., Winer, I.S., Barroilhet, L.M., Fu, S., McHale, M.T., Schilder, R.J., Farkkila, A., Curtis, J., Quinn, R., Whalen, C., Shapiro, G.I., and Matulonis, U.A.

Published
2019
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31. A PHASE 1 STUDY OF BET INHIBITION USING RG6146 IN RELAPSED/REFRACTORY (R/R) MYC-EXPRESSING DIFFUSE LARGE B CELL LYMPHOMA (DLBCL)

Author

Caimi, P.F., primary, Eder, J.P., additional, Jacobsen, E.D., additional, Jacobson, C.A., additional, LaCasce, A.S., additional, Shipp, M.A., additional, Chapuy, B., additional, Labriola-Tomphins, E., additional, Boisserie, F., additional, Passe, S., additional, Chesné, E., additional, Pierceall, W., additional, Zhi, J., additional, DeMario, M., additional, Vaishampayan, U., additional, Dowlati, A., additional, Shapiro, G.I., additional, Fisher, D.C., additional, and Armand, P., additional

Published
2017
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33. Supplementary Material for: Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer

Author

Barroso-Sousa R., Shapiro G.I., Tolaney S.M., Barroso-Sousa R., Shapiro G.I., and Tolaney S.M.

Abstract

Clinical and preclinical data support a significant role for inhibitors of the cyclin-dependent kinases (CDKs) 4 and 6 in the treatment of patients with breast cancer. Recently, based on data showing improvement in progression-free survival, the use of palbociclib (Ibrance; Pfizer, Inc.) in combination with endocrine agents was approved to treat patients with hormone receptor-positive advanced disease. Importantly, 2 other CDK4/6 inhibitors, abemaciclib (LY2835219; Lilly) and ribociclib (LEE011; Novartis), are in the late stage of clinical development. In this review, we will focus on clinical data on these 2 new drugs, highlighting their differences compared to palbociclib in terms of single-agent activity, central nervous system penetration, and common adverse events. In addition, we will present the ongoing clinical trials and discuss future directions in the field.

Published
2016
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35. 238 Reversal of primary and acquired PARP-inhibitor resistance in BRCA-mutated triple-negative breast cancers by inhibition of transcriptional cyclin-dependent kinases (CDKs)

Author

Johnson, S., primary, Johnson, N., additional, Chi, D., additional, Primack, B., additional, Cruz, C., additional, Stover, D., additional, Greifenberg, A.K., additional, Cao, S., additional, O'Connor, K., additional, Baselga, J., additional, Balmaña, J., additional, Serra, V., additional, Geyer, M., additional, D'Andrea, A., additional, Lim, E., additional, and Shapiro, G.I., additional

Published
2014
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39. Tidally induced lateral dispersion of the Storfjorden overflow plume

Author

Wobus, F., Shapiro, G.I., Huthnance, J.M., Maqueda, M.A.M., Aksenov, Y., Wobus, F., Shapiro, G.I., Huthnance, J.M., Maqueda, M.A.M., and Aksenov, Y.

Abstract

We investigate the flow of brine-enriched shelf water from Storfjorden (Svalbard) into Fram Strait and onto the western Svalbard Shelf using a regional set-up of NEMO-SHELF, a 3-D numerical ocean circulation model. The model is set up with realistic bathymetry, atmospheric forcing, open boundary conditions and tides. The model has 3 km horizontal resolution and 50 vertical levels in the sh-coordinate system which is specially designed to resolve bottom boundary layer processes. In a series of modelling experiments we focus on the influence of tides on the propagation of the dense water plume by comparing results from tidal and non-tidal model runs. Comparisons of non-tidal to tidal simulations reveal a hotspot of tidally induced horizontal diffusion leading to the lateral dispersion of the plume at the southernmost headland of Spitsbergen which is in close proximity to the plume path. As a result the lighter fractions in the diluted upper layer of the plume are drawn into the shallow coastal current that carries Storfjorden water onto the western Svalbard Shelf, while the dense bottom layer continues to sink down the slope. This bifurcation of the plume into a diluted shelf branch and a dense downslope branch is enhanced by tidally induced shear dispersion at the headland. Tidal effects at the headland are shown to cause a net reduction in the downslope flux of Storfjorden water into the deep Fram Strait. This finding contrasts previous results from observations of a dense plume on a different shelf without abrupt topography.

Published
2013

42. Dense water cascading off the continental shelf

Author

Shapiro, G.I., Huthnance, J.M., Ivanov, V.V., Shapiro, G.I., Huthnance, J.M., and Ivanov, V.V.

Abstract

Cascading is a specific type of buoyancy-driven current in which dense water formed by cooling, evaporation, or freezing in the surface layer over the continental shelf descends down the continental slope to a greater depth. We have identified, by world-wide trawling and analysis of raw databases, several distinct mechanisms of preconditioning for cascades. We have validated, where possible, existing theories and developed simple models, which allow estimation of the parameters for preconditioning, initiating, and down-slope fluxes as well as evolution of the temperature contrasts during cascading events. Compliance or noncompliance of observations with these simple and easy-to-use models has been related to the stage of cascade development and to local factors. Estimates of observed down-slope transport rates in case studies accord with theory, which is thereby substantially validated. Typical values of cascading transport rates were in the range 0.5–1.6 m2s−1. We hazard a very approximate global estimate of order 105 km3yr−1 or average 3 Sv based on our findings and previous studies.

Published
2003

43. The alternative density structures of cold/saltwater pools on a sloping bottom: the role of friction

Author

Shapiro, G.I., Hill, A.E., Shapiro, G.I., and Hill, A.E.

Abstract

Observed density sections through dense-water pools or lenses on sloping topography typically have an asymmetric structure. One side of the dense lens usually is bounded by isopycnals that slope steeply down to the seabed while, on the other side, the slope of isopycnals is more gentle. A common situation is for the steepest-sloping isopycnals to be on the upslope side of a lens (which is termed the “head-up” state), but the reverse is occasionally true (which is called the “head-down” state). Here a 1½-layer reduced-gravity model, which resolves the bottom boundary layer to provide physical insight into the three-dimensional evolution of these alternative forms, is used. It is found that the head-up state arises when the thickness of the central core of a lens exceeds about two Ekman depth scales, and the head-down state arises when the converse is true. The speed of along- and cross-slope motion of the central, thick core of a dense lens is also investigated, and the results from an ensemble of runs with the three-dimensional reduced-gravity model are found to accord suprisingly well with some approximations derived from bulk dynamics. From a practical point of view, the results concerning the shape of isopycnals bounding dense lenses on slopes can provide valuable information from which to infer important aspects of the underlying dynamics.

Published
2003

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