I-fibrinogen as an oncophilic radiodiagnostic agent: distribution kinetics in tumour-bearing mice.

Fibrinogen radioiodinated by the iodine monochloride method was tested as a tumour radiodiagnostic agent in mice. The I-fibrinogen cleared from the blood of tumour-bearing mice more rapidly than from that of normal mice, but it cleared from the whole body more slowly, suggesting it accumulated in a substantial tumour-related compartment in the abnormal mice. The tumour concentration steadily increased for 4 h after injection, at which time it reached a peak concentration of 11-4% of the injected dose/g. This concentration was higher than the peak concentration for Ga-citrate (not reached until 24 h) or any other oncophilic radiopharmaceutical tested in this tumour model. The early accumulation is consistent with the use of 123I as a tracer label for fibrinogen. A combination of the large tumour concentration of I-fibrinogen, an increased catabolic rate induced by chemical modification, and the exceptional nuclear properties of 123I for scintigraphic imaging, could lead to a very useful radiodiagnostic procedure for cancer

Rethinking immune checkpoint blockade: Beyond the T cell

The clinical success of immune checkpoint inhibitors has highlighted the central role of the immune system in cancer control. Immune checkpoint inhibitors can reinvigorate anti-cancer immunity and are now the standard of care in a number of malignancies. However, research on immune checkpoint blockade has largely been framed with the central dogma that checkpoint therapies intrinsically target the T cell, triggering the tumoricidal potential of the adaptive immune system. Although T cells undoubtedly remain a critical piece of the story, mounting evidence, reviewed herein, indicates that much of the efficacy of checkpoint therapies may be attributable to the innate immune system. Emerging research suggests that T cell-directed checkpoint antibodies such as anti-programmed cell death protein-1 (PD-1) or programmed death-ligand-1 (PD-L1) can impact innate immunity by both direct and indirect pathways, which may ultimately shape clinical efficacy. However, the mechanisms and impacts of these activities have yet to be fully elucidated, and checkpoint therapies have potentially beneficial and detrimental effects on innate antitumor immunity. Further research into the role of innate subsets during checkpoint blockade may be critical for developing combination therapies to help overcome checkpoint resistance. The potential of checkpoint therapies to amplify innate antitumor immunity represents a promising new field that can be translated into innovative immunotherapies for patients fighting refractory malignancies

Black Hole Evaporation in an Expanding Universe

We calculate the quantum radiation power of black holes which are asymptotic to the Einstein-de Sitter universe at spatial and null infinities. We consider two limiting mass accretion scenarios, no accretion and significant accretion. We find that the radiation power strongly depends on not only the asymptotic condition but also the mass accretion scenario. For the no accretion case, we consider the Einstein-Straus solution, where a black hole of constant mass resides in the dust Friedmann universe. We find negative cosmological correction besides the expected redshift factor. This is given in terms of the cubic root of ratio in size of the black hole to the cosmological horizon, so that it is currently of order $10^{-5} (M/10^{6}M_{\odot})^{1/3} (t/14 {Gyr})^{-1/3}$ but could have been significant at the formation epoch of primordial black holes. Due to the cosmological effects, this black hole has not settled down to an equilibrium state. This cosmological correction may be interpreted in an analogy with the radiation from a moving mirror in a flat spacetime. For the significant accretion case, we consider the Sultana-Dyer solution, where a black hole tends to increase its mass in proportion to the cosmological scale factor. In this model, we find that the radiation power is apparently the same as the Hawking radiation from the Schwarzschild black hole of which mass is that of the growing mass at each moment. Hence, the energy loss rate decreases and tends to vanish as time proceeds. Consequently, the energy loss due to evaporation is insignificant compared to huge mass accretion onto the black hole. Based on this model, we propose a definition of quasi-equilibrium temperature for general conformal stationary black holes.Comment: Accepted for publication in Class.Quant.Grav., 18 pages and 3 figure

Gravity from Spinors

We investigate a possible unified theory of all interactions which is based only on fundamental spinor fields. The vielbein and metric arise as composite objects. The effective quantum gravitational theory can lead to a modification of Einstein's equations due to the lack of local Lorentz-symmetry. We explore the generalized gravity with global instead of local Lorentz symmetry in first order of a systematic derivative expansion. At this level diffeomorphisms and global Lorentz symmetry allow for two new invariants in the gravitational effective action. The one which arises in the one loop approximation to spinor gravity is consistent with all present tests of general relativity and cosmology. This shows that local Lorentz symmetry is tested only very partially by present observations. In contrast, the second possible new coupling is severely restricted by present solar system observations.Comment: New material on absence of observational tests of local Lorentz invariance, 21 pages, to appear in Phys.Rev.

The Fulling-Unruh effect in general stationary accelerated frames

We study the generalized Unruh effect for accelerated reference frames that include rotation in addition to acceleration. We focus particularly on the case where the motion is planar, with presence of a static limit in addition to the event horizon. Possible definitions of an accelerated vacuum state are examined and the interpretation of the Minkowski vacuum state as a thermodynamic state is discussed. Such athermodynamic state is shown to depend on two parameters, the acceleration temperature and a drift velocity, which are determined by the acceleration and angular velocity of the accelerated frame. We relate the properties of Minkowski vacuum in the accelerated frame to the excitation spectrum of a detector that is stationary in this frame. The detector can be excited both by absorbing positive energy quanta in the "hot" vacuum state and by emitting negative energy quanta into the "ergosphere" between the horizon and the static limit. The effects are related to similar effects in the gravitational field of a rotating black hole.Comment: Latex, 39 pages, 5 figure

Intraoperative angiography via the popliteal artery: a useful technique for patients in the prone position

OBJECTIVE Intraoperative angiography can be a valuable tool in the surgical management of vascular disorders in the CNS. This is typically accomplished via femoral artery puncture; however, this can be technically difficult in patients in the prone position. The authors describe the feasibility of intraoperative angiography via the popliteal artery in the prone patient. METHODS Three patients underwent intraoperative spinal angiography in the prone position via vascular access through the popliteal artery. Standard angiography techniques were used, along with ultrasound and a micropuncture needle for initial vascular access. Two patients underwent intraoperative angiography to confirm the obliteration of dural arteriovenous fistulas. The third patient required unexpected intraoperative angiography when a tumor was concerning for a vascular malformation in the cervical spine. RESULTS All 3 patients tolerated the procedure without complication. The popliteal artery was easily accessed without any adaptation to typical patient positioning for these prone-position cases. This proved particularly beneficial when angiography was not part of the preoperative plan. CONCLUSIONS Intraoperative angiography via the popliteal artery is feasible and well tolerated. It presents significant benefit when obtaining imaging studies in patients in a prone position, with the added benefit of easy access, familiar anatomy, and low concern for catheter thrombosis or kinking

Effective Lagrangian for self-interacting scalar field theories in curved spacetime

We consider a self-interacting scalar field theory in a slowly varying gravitational background field. Using zeta-function regularization and heat-kernel techniques, we derive the one-loop effective Lagrangian up to second order in the variation of the background field and up to quadratic terms in the curvature tensors. Specializing to different spacetimes of physical interest, the influence of the curvature on the phase transition is considered.Comment: 14 pages, LaTex, UTF 29

Oncogenic Kras-mediated cytokine CCL15 regulates pancreatic cancer cell migration and invasion through ROS

Pancreatic ductal adenocarcinoma (PDAC) is well known for its high death rate due to prompt cancer metastasis caused by cancer cell migration and invasion within the early stages of its development. Here, we reveal a new function of cytokine CCL15, namely the upregulation of PDAC cell migration and invasion. We showed increased levels of CCL15 transcripts and protein expressions in human PDAC tissue samples, as well as in cultured cell lines. Furthermore, PDAC cells also expressed CCL15 receptors, including CCR1 and CCR3. Murine PDAC cell lines and tissues strengthened this finding. The manipulation of CCL15 in metastatic Panc-1 cells through CCL15 knockdown or CCL15 neutralization decreased Panc-1 cell motility and invasiveness. In addition, treating non-metastatic BxPC-3 cells with recombinant CCL15 accelerated the cell migration of BxPC-3. A reduction in the levels of reactive oxygen species (ROS) by either N-Acetyl-L-Cysteine treatment or p22phox knockdown led to a decrease in Panc-1 cell migration and a reversed effect on recombinant CCL15-promoted BxPC-3 cell movement. Importantly, the knockdown of oncogenic Kras in Panc-1 cells abolished CCL15 protein expression and impeded cell migration without affecting PDAC cell growth. Altogether, our work elucidates an additional molecular pathway of oncogenic Kras to promote PDAC metastasis through the upregulation of cell migration and invasion by the Kras downstream CCL15, a lesser-known cytokine within the cancer research field

Some general properties of the renormalized stress-energy tensor for static quantum states on (n+1)-dimensional spherically symmetric black holes

We study the renormalized stress-energy tensor (RSET) for static quantum states on (n+1)-dimensional, static, spherically symmetric black holes. By solving the conservation equations, we are able to write the stress-energy tensor in terms of a single unknown function of the radial co-ordinate, plus two arbitrary constants. Conditions for the stress-energy tensor to be regular at event horizons (including the extremal and ``ultra-extremal'' cases) are then derived using generalized Kruskal-like co-ordinates. These results should be useful for future calculations of the RSET for static quantum states on spherically symmetric black hole geometries in any number of space-time dimensions.Comment: 9 pages, no figures, RevTeX4, references added, accepted for publication in General Relativity and Gravitatio