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1.
Since the clinical introduction of anti-CD20 monoclonal antibodies into lymphoma treatment, immunologic approaches in lymphoma have made substantial progress. Advances in our understanding of tumor immunology have led to the development of strategies to overcome immunologic barriers responsible for an ineffective immune response. Specifically, therapeutic agents have been developed and tested against molecules that are responsible for T-cell exhaustion. The use of monoclonal antibodies against immune checkpoints in the adaptive immune system, such as programmed cell death-1 and cytotoxic T-lymphocyte-associated protein 4, has changed the landscape of cancer therapy including the treatment of lymphoma. This achievement has recently been accompanied by the development of novel immune checkpoint inhibitors targeting the innate immune system, including the CD47-SIRPα signaling pathway, and this approach has yielded promising results. To overcome impaired antigen presentation, antibody-based cytotoxic strategies, namely antibody-drug conjugates (polatuzumab vedotin and brentuximab vedotin) and bispecific T-cell or NK-cell engagers (blinatumomab, REGN1979, RG6206, and AFM13), have rapidly evolved with promising clinical activity. As additional tools become available for lymphoma treatment, formulation of safe, rational combination strategies to combine them with standard therapy will be of paramount importance. A successful approach to the treatment of lymphoma may require both an optimized anti-tumor immune response as well as effective depletion of malignant lymphoid cells. 相似文献
2.
C. J. Bowden W. D. Figg N. A. Dawson O. Sartor R. J. Bitton M. S. Weinberger Donna Headlee Eddie Reed C. E. Myers M. R. Cooper 《Cancer chemotherapy and pharmacology》1996,39(1-2):1-8
Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis,
but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer,
with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken
to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations
(275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous
infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted
in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed
in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml
for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed
this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response
rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses
were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy
with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred
with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well
tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional
therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but
it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment
of suramin’s activity in hormone-refractory prostate cancer.
Received: 9 June 1995/Accepted: 18 March 1996 相似文献
3.
胃粘膜上皮“适应性细胞保护”机制防止胃肿瘤发生的作用 总被引:4,自引:0,他引:4
投用致癌剂的对照组其胃肿瘤发生率为22.2%。若同时给予40%Z醇液空腹灌胃,则胃肿瘤发生率达55.9%。如在给乙醇液前15分钟,先给予4%的辣椒煎液灌胃,则胃肿瘤发生率只有20.0%,相近于对照组的水平(后2组差别有极显著意义,P<0.01)。这种给损伤剂(乙醇)之前先给予微刺激剂(辣椒)所产生的胃粘膜的保护作用,是通过促使胃粘膜上皮细胞合成内源性前列腺素(PGs)来实现的,是一种“适应性细胞保护”机制。这种保护胃粘膜的作用可降低胃肿瘤的发生率。 相似文献
4.
A. E. P. Villa E. M. Rouiller G. M. Simm P. Zurita Y. de Ribaupierre F. de Ribaupierre 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1991,86(3):506-517
Summary Single unit activity of 355 cells was recorded in the auditory thalamus of anesthetized cats before, during, and after the inactivation by cooling of the ipsilateral primary auditory cortex (AI). Most of the units (n = 288) showed similar functional characteristics of firing before and after the cryogenic blockade of AI. The spontaneous firing rate remained unchanged by cooling in 20% of the units and decreased in the majority of them (60%). In some regions, i.e. dorsal division of the medial geniculate body (MGB), lateral part of the posterior group of the thalamus, and auditory sector of the reticular nucleus of the thalamus, the maximum firing rate evoked by white noise bursts was generally affected by cooling in the same direction and to the same extent as the spontaneous activity. Units in the ventral division of MGB showed a characteristic increase of signal-to-noise ratio during cortical cooling. The corticofugal modulation led to the appearance or disappearance of the best frequency of tuning in 51 units and changed it by more than 0.5 octave in 34 units. The bandwidths of different response patterns to pure tones stimulation were used to define a set of functional properties. During cryogenic blockade of AI, two cortically modulated sub-populations of units were usually distinguished that exhibited changes for a given functional property. The complexity and diversity of the effects of cortical inactivation suggest that the corticothalamic projection may be the support for selective operations such as an adaptive filtering of the incoming acoustic signal at the thalamic level adjusted as a function of cortical activity. 相似文献
5.
High-protein Weight-loss Diets: Are They Safe and Do They Work? A Review of the Experimental and Epidemiologic Data 总被引:6,自引:0,他引:6
Julie Eisenstein M.D. Susan B. Roberts Ph.D. Gerard Dallal Ph.D. Edward Saltzman M.D. 《Nutrition reviews》2002,60(7):189-200
Recommendations for increased consumption of protein are among the most common approaches of popular or fad diets. This review summarizes the effects of dietary protein on satiety, energy intake, thermogenesis, and weight loss, as well as its effect on a variety of health outcomes in adults. In short-term studies, dietary protein modulates energy intake via the sensation of satiety and increases total energy expenditure by increasing the thermic effect of feeding. Whereas these effects did not contribute to weight and fat loss in those studies in which energy intake was fixed, one ad libitum study does suggest that a high-protein diet results in a greater decrease in energy intake, and therefore greater weight and fat loss. In terms of safety, there is little long-term information on the health effects of high-protein diets. From the available data, however, it is evident that the consumption of protein greater than two to three times the U.S. Recommended Daily Allowance contributes to urinary calcium loss and may, in the long term, predispose to bone loss. Caution with these diets is recommended in those individuals who may be predisposed to nephrolithiasis or kidney disease, and particularly in those with diabetes mellitus. 相似文献
6.
Cristiano Feijó Andrade Thomas K. Waddell Shaf Keshavjee Mingyao Liu 《American journal of transplantation》2005,5(5):969-975
Traditionally, the recognition and tolerance of transplanted grafts has been considered to be within the realm of the adaptive immune system. Innate immunity, on the other hand, as the first line of host defense, plays a role in fighting against invading microorganisms. Recently, with the discovery of the Toll-like receptors (TLRs), the role of innate immune responses in the control of adaptive immunity has become a new area of interest. Emerging evidence suggests that in addition to responding to pathogen-associated molecular patterns of microorganisms, TLRs can be activated by endogenous ligands, expressed by mammalian cells. These 'danger signals' may participate in ischemia-reperfusion related organ damage and subsequently influence function and survival of transplanted grafts. Furthermore, it has been suggested that adaptive immune responses can enhance the acute inflammatory responses controlled by innate immunity in organ transplantation. This review addresses the potential involvement of TLRs in different stages of organ transplantation. Intriguing and controversial findings are presented and discussed in order to stimulate more attention to this emerging and potentially important area of research in organ transplantation. 相似文献
7.
目的:减少患者对外固定支架治疗胫骨骨折的恐惧心理,提高患者的适应能力,促进骨折愈合,预防并发症。方法:运用美国护理专家罗依的适应模式,分析113例患者受到的主要刺激,根据护理目标,制订具体护理措施,帮助患者找出适应性问题,做出适应性反应。结果:113例患者全部适应外固定支架的治疗,完成了护理目标。护理效果良好,早期即能下床活动,骨折愈合快,出院随访,无因该治疗方法出现并发症。结论:罗依的适应模式使患者配合护理,能不断识别环境中的新刺激,调整适应方式,做出适应性反应,达到预期目标。 相似文献
8.
Mechanotransduction of bone cells<Emphasis Type="Italic">in vitro</Emphasis>: Mechanobiology of bone tissue 总被引:11,自引:0,他引:11
Mullender M El Haj AJ Yang Y van Duin MA Burger EH Klein-Nulend J 《Medical & biological engineering & computing》2004,42(1):14-21
Mechanical force plays an important role in the regulation of bone remodelling in intact bone and bone repair. In vitro, bone
cells demonstrate a high responsiveness to mechanical stimuli. Much debate exists regarding the critical components in the
load profile and whether different components, such as fluid shear, tension or compression, can influence cells in differing
ways. During dynamic loading of intact bone, fluid is pressed through the osteocyte canaliculi, and it has been demonstrated
that fluid shear stress stimulates osteocytes to produce signalling molecules. It is less clear how mechanical loads act on
mature osteoblasts present on the surface of cancellous or trabecular bone. Although tissue strain and fluid shear stress
both cause cell deformation, these stimuli could excite different signalling pathways. This is confirmed by our experimental
findings, in human bone cells, that strain applied through the substrate and fluid flow stimulate the release of signalling
molecules to varying extents. Nitric oxide and prostaglandin E2 values increased by between two- and nine-fold after treatment with pulsating fluid flow (0.6±0.3 Pa). Cyclic strain (1000
μstrain) stimulated the release of nitric oxide two-fold, but had no effect on prostaglandin E2. Furthermore, substrate strains enhanced the bone matrix protein collagen I two-fold, whereas fluid shear caused a 50% reduction
in collagen I. The relevance of these variations is discussed in relation to bone growth and remodelling. In applications
such as tissue engineering, both stimuli offer possibilities for enhancing bone cell growth in vitro. 相似文献
9.
We have studied the influence of a temperature-sensitive cdc2-1 mutation in DNA polymerase on the selection-induced mutation occurring at the LYS-2 locus in the yeast Saccharomyces cerevisiae. It was found that in cells plated on synthetic complete medium lacking only lysine, the numbers of Lys+ revertant colonies accumulated in a time-dependent manner in the absence of any detectable increase in cell number. When cdc2-1 mutant cells, after selective plating, were incubated at the restrictive temperature of 37°C for 5 h daily for 7 days, the frequency of an adaptive reversion of lys
- Lys+ was significantly higher than the frequency in cells incubated only at the permissive temperature, or in wild-type cells incubated either at 23°C or 37°C. Therefore, when the proof-reading activity of DNA polymerase is impaired under restrictive conditions, the frequency of adaptive mutations is markedly enhanced. 相似文献
10.
The paper presents an adaptive noise canceller (ANC) filter using an artificial neural network for real-time removal of electro-oculogram
(EOG) interference from electro-encephalogram (EEG) signals. Conventional ANC filters are based on linear models of interference.
Such linear models provide poorer prediction for biomedical signals. In this work, a recurrent neural network was employed
for modelling the interference signals. The eye movement and eye blink artifacts were recorded by the placing of an electrode
on the forehead above the left eye and an electrode on the left temple. The reference signal was then generated by the data
collected from the forehead electrode being added to data recorded from the temple electrode. The reference signal was also
contaminated by the EEG. To reduce the EEG interference, the reference signal was first low-pass filtered by a moving averaged
filter and then applied to the ANC. Matlab Simulink was used for real-time data acquisition, filtering and ocular artifact
suppression. Simulation results show the validity and effectiveness of the technique with different signal-to-noise ratios
(SNRs) of the primary signal. On average, a significant improvement in SNR up to 27 dB was achieved with the recurrent neural
network. The results from real data demonstrate that the proposed scheme removes ocular artifacts from contaminated EEG signals
and is suitable for real-time and short-time EEG recordings. 相似文献