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排序方式: 共有1551条查询结果,搜索用时 31 毫秒
1.
John Goffin Stefan Baral Dongsheng Tu Dora Nomikos Lesley Seymour 《Clinical cancer research》2005,11(16):5928-5934
PURPOSE: Tumor responses in early-phase trials are used to determine whether new agents warrant further study. Given that spontaneous regressions are observed in melanoma and renal cell carcinoma, this study assessed whether tumor responses, particularly in these two tumor types, predict for future regulatory drug approval. EXPERIMENTAL DESIGN: The literature was reviewed to assess tumor response rates to cytotoxic agents in phase I and II trials in the following solid tumors: melanoma, renal cell carcinoma, non-small-cell lung cancer, breast cancer, ovarian cancer, colorectal cancer, and other solid tumors. Response rates were categorized and the relationship of these categories to the end point of regulatory drug approval was determined. RESULTS: Fifty-eight drugs were assessed in 100 phase I trials, and 46 of these drugs were also studied in 499 phase II trials. Higher overall response rates in both phase I trials (P = 0.03) and phase II trials (P < 0.0001) were predictive of regulatory approval. However, response in melanoma or renal cell carcinoma was not predictive for either phase I or phase II studies. CONCLUSIONS: For cytotoxic agents, although overall objective response rates reliably predict subsequent marketing approval, isolated responses in melanoma and renal cell carcinoma are not predictive. 相似文献
2.
Patric M Schiltz German G Gomez Susana B Read Nisha V Kulprathipanja Carol A Kruse 《Journal of interferon & cytokine research》2002,22(12):1209-1216
To enhance the efficacy of cellular immunotherapy for gliomas, we tested the concept of using proinflammatory cytokine treatment with interferon-gamma (IFN-gamma) or interleukin-1beta (IL-1beta) or both to render glioma cells more susceptible to cytolysis by alloreactive cytotoxic T lymphocytes (aCTL). The cytokines, separately or in combination, were able to upregulate major histocompatibility complex (MHC) class I antigen or intercellular adhesion molecule-1 (ICAM-1) on Fischer rat 9L gliosarcoma cells. 9L cells were incubated in vitro for 24, 48, or 72 h with varying concentrations of rat IFN-gamma (0-2000 U/ml) or recombinant human IL-1 (rHUIL-1) (0-1000 U/ml) or both. By 48 h, IFN-gamma (500 U/ml) maximally induced the percentage of positive expressing cells and the relative antigen density of MHC class I and ICAM-1 on 9L cells, whereas IL-1 induced only ICAM-1 expression. Simultaneous incubation of IL-1 with IFN-gamma did not further affect the induction of class I on 9L cells more than that achieved with IFN-gamma alone. 9L cells with upregulated MHC class I and ICAM-1 expression were more sensitive to lysis by aCTL in in vitro cytotoxicity assays, regardless of whether the precursor aCTL came from naive or from 9L-immunized rats. Furthermore, inhibition of 9L cytotoxicity in assays that included blocking antibodies to MHC class I or to ICAM-1 revealed that T cell receptor (TCR) interactions with MHC class I and that ICAM-1 interactions with lymphocyte function-associated-1 (LFA-1) antigen account for a portion of the glioma lysis by aCTL. 相似文献
3.
4.
Mathur SK Singh S Marwah N Jindal R Arora B Rattan KN 《Indian journal of pathology & microbiology》2004,47(2):261-263
Pancreatoblastoma or infantile pancreatic carcinoma is a rare pancreatic tumor with distinct acinar and squamoid cell differentiation that generally affects infants and young children. Ultrasound and CT scan may be useful but preoperative diagnosis is often quite difficult. The outcome is generally favourable. A such case of 10 years old boy with an abdominal mass is being presented. 相似文献
5.
Henry R. Halperin Joshua E. Tsitlik Rafael Beyar Nisha Chandra Alan D. Guerci 《Annals of biomedical engineering》1987,15(3-4):385-403
Whether blood flow during cardiopulmonary resuscitation (CPR) results from intrathoracic pressure fluctuations or direct cardiac
compression remains controversial. We developed a mathematical model that predicts that blood flow due to intrathoracic pressure
fluctuations should be insensitive to compression rate over a wide range but dependent on the applied force and compression
duration. If direct compression of the heart plays a major role, however, the model predicts that flow should be dependent
on compression rate and force, but above a threshold, insensitive to compression duration. These differences in hemodynamics
produced by changes in rate and duration form a basis for determining whether blood flow during CPR results from intrathoracic
pressure fluctuations or from direct cardiac compression. The model was validated for direct cardiac compression by studying
the hemodynamics of cyclic cardiac deformation following thoracotomy in four anesthetized, 21–32-kg dogs. As predicted by
the model, there was no change in myocardial or cerebral perfusion pressures when the duration of compression was increased
from 15% to 45% of the cycle at a constant rate of 60/min. There was, however, a significant increase in perfusion pressures
when rate was increased from 60 to 150/min at a constant duration of 45%. The model was validated for intrathoracic pressure
changes by studying the hemodynamics produced by a thoracic vest (vest CPR) in eight dogs. The vest contained a bladder that
was inflated and deflated. Vest CPR changed intrathoracic pressure without direct cardiac compression, since sternal displacement
was <0.8 cm. As predicted by the model and opposite to direct cardiac compression, there was no change in perfusion pressures
when the rate was increased from 60 to 150/min at a constant duration of 45% of the cycle. Manual CPR was then studied in
eight dogs. There was no surgical manipulation of the chest. Myocardial and cerebral blood flows were determined with radioactive
microspheres and behaved as predicted from the model of intrathoracic pressure, not direct cardiac compression. At nearly
constant peak sternal force (378–426 N), flow was significantly increased when the duration of compression was increased from
short (13%–19% of the cycle) to long (40%–47%), at a rate of 60/min. Flow was unchanged, however, for an increase in rate
from 60 to 150/min at constant compression duration. In addition, myocardial and cerebral flow correlated with their respective
perfusion pressures. Thus vital organ perfusion pressures and flow for manual external chest compression are dependent on
the duration of compression, but not on rates of compression of 60 and 150/min. These data are of course similar to those
produced by vest CPR, where intrathoracic pressure is manipulated without sternal displacement, and to those predicted for
movement of blood by intrathoracic pressure changes. These data are, however, opposite to those produced by cardiac deformation
and to those predicted for movement blood by direct cardiac compression. We conclude that intrathoracic pressure fluctuations
generate blood flow during manual CPR. 相似文献
6.
Epilepsy affects approximately 1% of the population worldwide, and there is a pressing need to develop new anti-epileptic drugs (AEDs) and understand their mechanisms of action. Levetiracetam (LEV) is a novel AED and despite its increasingly widespread clinical use, its mechanism of action is as yet undetermined. Intracellular calcium ([Ca2+]i) regulation by both inositol 1,4,5-triphosphate receptors (IP3R) and ryanodine receptors (RyR) has been implicated in epileptogenesis and the maintenance of epilepsy. To this end, we investigated the effect of LEV on RyR and IP3R activated calcium-induced calcium release (CICR) in hippocampal neuronal cultures. RyR-mediated CICR was stimulated using the well-characterized RyR activator, caffeine. Caffeine (10 mM) caused a significant increase in [Ca2+]i in hippocampal neurons. Treatment with LEV (33 μM) prior to stimulation of RyR-mediated CICR by caffeine led to a 61% decrease in the caffeine induced peak height of [Ca2+]i when compared to the control. Bradykinin stimulates IP3R-activated CICR—to test the effect of LEV on IP3R-mediated CICR, bradykinin (1 μM) was used to stimulate cells pre-treated with LEV (100 μM). The data showed that LEV caused a 74% decrease in IP3R-mediated CICR compared to the control. In previous studies we have shown that altered Ca2+ homeostatic mechanisms play a role in seizure activity and the development of spontaneous recurrent epileptiform discharges (SREDs). Elevations in [Ca2+]i mediated by CICR systems have been associated with neurotoxicity, changes in neuronal plasticity, and the development of AE. Thus, the ability of LEV to modulate the two major CICR systems demonstrates an important molecular effect of this agent on a major second messenger system in neurons. 相似文献
7.
Marwah N Gupta S Mathur SK Singh S Marwah S Arora B 《Indian journal of pathology & microbiology》2003,46(1):65-66
Primary malignant lymphomas of the breast (PBL) are uncommon constituting only 0.04 to 0.53% of malignant breast neoplasms. We wish to report the clinical, cytological and histologic findings of PBL diagnosed in a 52 years old female. 相似文献
8.
Selvaraj P Chandra G Jawahar MS Rani MV Rajeshwari DN Narayanan PR 《Journal of clinical immunology》2004,24(5):523-532
The regulatory role of vitamin D receptor (VDR) gene variants of Bsm I, Apa I, Taq I, and Fok I polymorphisms on vitamin D(3)-modulated macrophage phagocytosis with live Mycobacterium tuberculosis and lymphoproliferative response to M. tuberculosis culture filtrate antigen (CFA) was studied in patients with pulmonary tuberculosis (n = 46) and in normal healthy subjects (NHS) (n = 64). Vitamin D(3) at a concentration of 1 x 10(-7) M enhanced the phagocytic potential of normal subjects who had a phagocytic index of less than 20%. This increase was seen in subjects with the genotypes BB (p = 0.017), AA (p = 0.016), tt (p = 0.034), and FF (p = 0.013) and the extended genotype BBAAtt (p = 0.034). Normal subjects with BBAAtt performed better phagocytosis than individuals with bbaaTT genotype (p = 0.034). Vitamin D(3) at 10(-9), 10(-8), and 10(-7) M concentrations suppressed the lymphoproliferative response to CFA antigen in normal subjects. This decreased lymphocyte response was observed in normal individuals with the genotypes BB (p = 0.0009), tt (p = 0.016), and FF (p = 0.008) and the extended genotype BBAAtt (p = 0.02). Addition of vitamin D(3) had no significant effect on macrophage phagocytosis and lymphoproliferative response to CFA in pulmonary TB patients. This may be due to the unresponsive nature of the cells to the action of vitamin D(3) or the downregulated VDR expression by virtue of the disease, which renders them inactive. The genotypes BB, tt, and the extended genotype BBAAtt may be associated with increased expression of VDR which in turn regulate the action of vitamin D(3) and modulate the immune functions to M. tuberculosis in NHS. 相似文献
9.
Singh P Mathur SK Kundu ZS Singh S Marwah N Arora B 《Indian journal of pathology & microbiology》2005,48(2):206-208
Extraskeletal chondroma is a rare entity. A fairly benign condition, it is usually seen in adults. It presents as an enlarging mass, most commonly in the hand. Local excision is the treatment of choice. We present a case of extraskeletal chondroma of hand in a 12 year male child. Its variable histological appearance not infrequently leads to a mistaken diagnosis of chondrosarcoma. 相似文献
10.
The prognostic relevance of phytohemagglutinin (PHA) and purified protein derivative (PPD) lymphocyte reactivity at diagnosis and after radiotherapy was evaluated in breast cancer patients. The patients were followed up to 13 years and the prognostic value expressed as ratios between observed number of deaths and "estimated" number of deaths under the null hypothesis. There was no significant association between the initial PHA and PPD reactivity and the survival of the patients. On the other hand, mortality up to 8 years after radiotherapy was significantly higher for patients with low PHA and PPD reactivity at completion of treatment. Furthermore, patients who had higher than average PPD reactivity 6 to 10 months after radiotherapy, seemed to have a higher survival rate. The prognostic relevance of postirradiation lymphocyte reactivity was only to some extent explained by clinical stage. 相似文献