54 research outputs found
Intraoperative subcutaneous or intrasplenic vaccination with modified autologous tumor cells leads to enhanced survival in a mouse tumor model
No full textS.379-388Purpose: We investigated the effect of intraoperative intrasplenic or subcutaneous vaccination with modified tumor cells on tumor progression in a mouse model. Methods: Pre-established B16 melanomas on C57/Bl6 mice were surgically removed; mice were vaccinated intraoperatively with B16 cells transfected with an IL-12-encoding pRSC construct, the empty plasmid, or B16 frozen cells. Cells were given either intrasplenically or subcutaneously. Intrasplenic effects of vaccination were examined along with survival data. Mice without tumor recurrence underwent a second tumor implantation. Results: Animals administered IL-12 pRSC cells showed significant alterations in the spleen, such as higher percentages of (activated) CD4+ and CD8+ T cells and tumor-specific CD4+ T cells among splenocytes. The tumor recurrence rate after resection ranged from 13 to 36%. Cases with recurrent tumors in particular benefited in all therapy groups, resulting in enhanced (tumor-free) survival, reduced tumor growth and lower metastasis rates. Following macroscopic complete tumor resection, the optimum outcome resulted from vaccination with IL-12 pRSC cells into the spleen and subcutaneously administered frozen cells. Survival times were enhanced in all therapy groups after tumor reimplantation, although results were not significant. Conclusions: Intraoperative whole-cell vaccination with autologous tumor cells yields promising data, and could be considered as a future option in adjuvant cancer therapy.132Nr.
First-line immune-checkpoint inhibitor plus chemotherapy versus chemotherapy alone for extensive-stage small-cell lung cancer: a meta-analysis
No full textInternational audienceIntroduction: Platin-based chemotherapy (CT) has long been the first-line standard-of-care for patients with extensive-stage small-cell lung cancer (ES–SCLC). Adding immune-checkpoint inhibitor(s) to CT (ICI+CT) in this setting is an option of interest, although its benefit is apparently modest. Methods: This meta-analysis was conducted on randomized trials comparing first-line ICI+CT versus CT alone for ES–SCLC. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), response at 12 months and adverse events (AEs). Subgroup analyses were computed according to the immunotherapy used, performance status (PS), age, platinum salt, liver metastases and brain metastases at diagnosis. Results: The literature search identified one randomized phase II (ECOG-ACRIN-5161) and four phase III trials (CASPIAN, IMPOWER-133, KEYNOTE-604 and Reck et al. 2016) that included 2775 patients (66% males, 95% smokers, median age: 64 years, PS = 0 or 1). ICI+CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS [0.82 (0.75–0.89); p < 0.00001] and PFS [0.81 (0.75–0.87); p < 0.00001], with OS benefits for anti-PD-L1 [0.73 (0.63–0.85); p < 0.0001] or anti-PD-1 [0.76 (0.63–0.93); p < 0.006] but not for anti-CTLA-4 [0.90 (0.80–1.01), p = 0.07]. ORRs for ICI+CT or CT alone were comparable [odds ratio 1.12 (0.97–1.00); p = 0.12], but responses at 12 months favored ICI+CT [4.16 (2.81–6.17), p < 0.00001]. Serious grade-3/4 AEs were more frequent with ICI+CT [odds ratio 1.18 (1.02–1.37); p = 0.03]. Compared with CT, no ICI+CT benefit was found for ES–SCLC with brain metastases at diagnosis [HR 1.14 (0.87–1.50); p = 0.34]. Conclusions: First-line ICI+CT appears to be superior to CT alone for ES–SCLC except for patients with brain metastases at diagnosis
Randomized phase II study of pemetrexed in combination with cisplatin or carboplatin as first-line chemotherapy in advanced non-small cell lung cancer.
No full textTopologies of Complex Networks: Functions and Structures
No full textDuring the last decade, significant efforts have been made toward improving our understanding of the topological structures underlying complex networks and illuminating some of the intriguing large-scale properties exhibited by these systems. The dominant theme of these efforts has been on studying the graph-theoretic properties of the corresponding connectivity structures and on developing universal theories and models that transcend system-specific details and describe the different systems well in a statistical sense.
However, in this thesis we argue that these efforts have had limited success and are in need of substantial correction. Using a highly engineered system, the Internet, as a case study we demonstrate that networks are designed for a purpose, and ignoring that aspect or obscuring it with the use of some generic but random mechanism can result in models that misrepresent what matters for system functions. By accounting in a minimal manner for both the functional requirements and structural features inherent in the design of an engineered system, we propose an alternative, optimization-based modeling approach that highlights the necessary trade-offs between system performance and the technological and economic constraints that are crucial when designing the system. We show that our proposed approach yields network models that not only match the large-scale graph-theoretic properties of measured router-level topologies well but are also fully consistent with engineering intuition and networking reality, especially as far as their performance aspects and robustness properties are concerned. In fact, we show that our design-inspired network models can be easily distinguished from previously considered probabilistic network models and efficiently achieve the level of performance for which they were designed in the first place.
While this thesis focuses on the Internet, it has much broader implications for complex networks and graph theory generally. To better differentiate between different graphs that are identical in certain graph statistics, we introduce a structural metric, the s-metric, and demonstrate that it provides insights into the diversity of graphs constrained by certain common properties and sheds new light on many classic graph concepts such as the various notions of self-similarity, likelihood, and assortativity. Our s-metric clarifies much of the confusion surrounding the sensational qualitative claims in the current graph theory literature for complex networks and offers a rigorous and quantitative alternative.
Moreover, to examine the space of graphs that satisfy certain common properties, we propose a new approach that is based on establishing a link between two graphs if and only if one can be obtained from the other via a local transformation. Exploring the resulting connected space of graphs by dividing it into countable subspaces provides a much clearer picture on the whole space. We also show that this space of graphs has a rich and interesting structure and that some properties of the latter can be related to features of the individual graphs in this space (e.g., degree variability of a node in the space of graphs and the s-metric for g).</p
A randomised multi-centre phase-II trial to assess the effect of dose splitting of carboplatin (CARBO) in comparison to a single application of carboplatin in a gemcitabine (GEM)/carboplatin regime for stage IIIB and IV non small cell lung cancer (NSCLC)
No full textFinal results of a pharmacokinetic (PK) study of capecitabine (X) in combination with oxaliplatin (O) for patients (pts) with metastatic colorectal cancer (MCRC)
No full textBevacizumab (Bev) or cetuximab (Cet) plus chemotherapy after progression with bevacizumab plus chemotherapy in patients with wild-type (WT) KRAS metastatic colorectal cancer (mCRC): Final analysis of a French randomized, multicenter, phase II study (PRODIGE 18)
No full textIF 11.855International audienc
Vascular and renal effects of anti-angiogenic drugs: recommendations for French practice. (The Company of Nephrology, American Society of Hypertension, National Educational Association of Teachers of Therapeutics and Francophone Federation of Digestive Cancerology)
No full textNational audienceAngiogenesis inhibitor drugs (bevacizumab, sunitinib, sorafenib, etc.) are now widely used for treatment of cancers, including colorectal, advanced renal-cell and hepatocellular carcinomas, breast cancer). Vascular and renal side-effects of the drugs are not well known. Hypertension is one of the most common side effects. Incidence of hypertension may be different among angiogenis inhibitors, and seems dose-depend. Arterial pressure can usually be controlled with antihypertensive medications, and treatment with angiogenesis inhibitors can be continued in most cases; however, serious hypertension-induced side effects were reported included malignant hypertension, stroke and reversible posterior leucoencephalopathy. Renal damage is infrequently reported: usually reversible mild or moderate proteinuria and in some rare cases nephritic syndrome, acute renal dysfunction, proliferative or collapsing glomerulonephritis, interstitial nephritis and thrombotic microangiopathy. Prolongation of the QT interval, congestive heart failure and left ventricular dysfunction have been reported in patients using tinibs. In the present guidelines, we recommend: 1) before the 1st administration of angiogenesis inhibitors: giving acute i.v. or oral antihypertensive medications in a patient with arterial pressure must be avoided; postponing the administration because of hypertension is not recommended; 2) initial workup should include ambulatory measurement of arterial pressure ( by the general practitioner or by the patient using home blood pressure ( 3 times in the morning and in the evening during three consecutive days) with a validated (cf.: http://afssaps.sante.fr/) upper arm device. Using 24-hour ambulatory blood pressure measurement is optional; 3) urine dipstick ( and quantification is positive) and estimated glomerular filtration rate ( using abbreviated MDRD rather than Cockcroft-Gault formula) must be performed before treatment and regularly during follow-up; 4) therapeutic management must be done in accordance with national or international guidelines ( in France: http://www.hassante.fr/); 5) Optimal care is best achieved within a network of professionals including general practitioners, oncologists, cardiologists and nephrologists
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State of the Art in EM Field Computation
No full textThis paper presents the advances in electromagnetic (EM) field computation that have been enabled by the US DOE SciDAC Accelerator Science and Technology project which supports the development and application of a suite of electromagnetic codes based on the higher-order finite element method. Implemented on distributed memory supercomputers, this state of the art simulation capability has produced results which are of great interest to accelerator designers and with realism previously not possible with standard codes. Examples from work on the International Linear Collider (ILC) project are described
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