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排序方式: 共有628条查询结果,搜索用时 15 毫秒
21.
Cardoso AA; Schultze JL; Boussiotis VA; Freeman GJ; Seamon MJ; Laszlo S; Billet A; Sallan SE; Gribben JG; Nadler LM 《Blood》1996,88(1):41-48
Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance. 相似文献
22.
Quality control of multidrug resistance assays in adult acute leukemia: correlation between assays for P-glycoprotein expression and activity 总被引:1,自引:5,他引:1
Broxterman HJ; Sonneveld P; Feller N; Ossenkoppele GJ; Wahrer DC; Eekman CA; Schoester M; Lankelma J; Pinedo HM; Lowenberg B; Schuurhuis GJ 《Blood》1996,87(11):4809-4816
We have compared multiple assays for the P-glycoprotein (Pgp/MDR1) phenotype in fresh and thawed adult acute leukemia to validate and quantitate measures for the expression and function of Pgp. The results are related to the Pgp-expressing KB8 and KB8-5 call lines. The most sensitive assay was the measurement of modulation of the rhodamine 123 (R123) fluorescence by 2 micromol/L PSC833, followed by the modulation of the probe calcein-AM. We also found a good intralaboratory and interlaboratory correlation between the values of the R123/PSC833 assay for fresh as well as thawed samples. In addition, the affects of PSC833 on 3H-daunorubicin (DNR) accumulation, DNR fluorescence, and 3H- vincristine accumulation were very similar. The correlation between the DNR/PSC833 and R123/PSC833 test was r = .86 (N = 51). The modulation of drug accumulation by 8 micromol/L verapamil was the some as the PSC833 effect for DNR (117%, N = 21), but was higher for vincristine in every single case (161% v 121%, N = 22; P< .001), indicating additional verapamil effects, not related to Pgp. The correlation of the staining of viable cells for Pgp with the monoclonal antibody MRK16 was r = .77 (N = 52) for the R123/PSC833 functional test and r = .84 (N = 50) for the DNR/PSC833 test. From these results it could be calculated that a maximal increase of the mean DNR accumulation of about 50% can be achieved by blocking Pgp pump activity with PSC833 in leukemic blast samples with the highest mean Pgp expression. Subpopulations of blast calls with higher Pgp activity are likely to be present. Their relevance has to be studied further. The methods outlined here allow the reliable, quantitative monitoring of the Pgp/MDR1 phenotype in leukemias in multicentered, clinical Pgp modulation studies. 相似文献
23.
Repair of large midline incisional hernias with polypropylene mesh: Comparison of three operative techniques 总被引:9,自引:0,他引:9
de Vries Reilingh TS van Geldere D Langenhorst BLAM de Jong D van der Wilt GJ van Goor H Bleichrodt RP 《Hernia》2004,8(1):56-59
Polypropylene mesh is widely used for the reconstruction of incisional hernias that cannot be closed primarily. Several techniques have been advocated to implant the mesh. The objective of this study was to evaluate, retrospectively, early and late results of three different techniques, onlay, inlay, and underlay. The records of 53 consecutive patients with a large midline incisional hernia — 25 women and 28 men, mean age 60.4 (range 28–94) — were reviewed. Polypropylene mesh was implanted using the onlay technique in 13 patients, inlay in 23 patients, and underlay in 17 patients. Either the greater omentum or a polyglactin mesh was interponated between the mesh and the viscera. The records of these 53 patients were reviewed with respect to: size and cause of the hernia, pre- and postoperative mortality and morbidity, with special attention to wound complications. Patients were invited to attend the outpatient clinic at least 12 months after implantation of the mesh for physical examination of the abdominal wall. Postoperative complications occurred in 14 (26.4%) patients. The onlay technique had significantly more complications, as compared to both other techniques. Reherniation occurred in 15 (28.3%) patients. The reherniation rate of the inlay technique was significantly higher than after the underlay technique (44% vs 12%, P=0.03) and tended to be higher than the onlay technique (44% vs 23%, P=0.22). Repair of large midline incisional hernias with the use of a polypropylene mesh carries a high risk of complications and has a high reherniation rate. The underlay technique seems to be the better technique. 相似文献
24.
Intraoperative ultrasound examination of the brain 总被引:5,自引:0,他引:5
In a preliminary demonstration of cranial intraoperative real-time ultrasound, both supratentorial and posterior fossa scans displayed the pertinent anatomy. A grade III astrocytoma was visualized on the supratentorial scan as well. Ultrasound may be valuable for surgical planning and biopsy procedures because of its reliable depiction of intracranial anatomy and ease of use. 相似文献
25.
Francis W. Hunter Jagdish K. Jaiswal Daniel G. Hurley H.D. Sarath Liyanage Sarah P. McManaway Yongchuan Gu Susan Richter Jingli Wang Moana Tercel Cristin G. Print William R. Wilson Frederik B. Pruijn 《Biochemical pharmacology》2014
The nitro-chloromethylbenzindoline prodrug SN29428 has been rationally designed to target tumour hypoxia. SN29428 is metabolised to a DNA minor groove alkylator via oxygen-sensitive reductive activation initiated by unknown one-electron reductases. The present study sought to identify reductases capable of activating SN29428 in tumours. Expression of candidate reductases in cell lines was modulated using forced expression and, for P450 (cytochrome) oxidoreductase (POR), by zinc finger nuclease-mediated gene knockout. Affymetrix microarray mRNA expression of flavoreductases was correlated with SN29428 activation in a panel of 23 cancer cell lines. Reductive activation and cytotoxicity of prodrugs were measured using mass spectrometry and antiproliferative assays, respectively. SN29428 activation under hypoxia was strongly attenuated by the pan-flavoprotein inhibitor diphenyliodonium, but less so by knockout of POR suggesting other flavoreductases contribute. Forced expression of 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), as well as POR, increased activation of SN29428 in hypoxic HCT 116 cells. SN29428 activation strongly correlated with expression of POR and also FAD-dependent oxidoreductase domain containing 2 (FOXRED2), in cancer cell lines. This association persisted after removing the effect of POR enzyme activity using first-order partial correlation. Forced expression of FOXRED2 increased SN29428 activation and cytotoxicity in hypoxic HEK293 cells and also increased activation of hypoxia-targeted prodrugs PR-104A, tirapazamine and SN30000, and increased cytotoxicity of the clinical-stage prodrug TH-302. Thus this study has identified three flavoreductases capable of enzymatically activating SN29428, one of which (FOXRED2) has not previously been implicated in xenobiotic metabolism. These results will inform future development of biomarkers predictive of SN29428 sensitivity. 相似文献
26.
27.
OBJECTIVE: The purpose of this study was to determine the effect of left-to-right shunting on the resting energy expenditure (REE), total energy expenditure (TEE), and energy intake in a group of 3- to 5-month-old infants with moderate to large unrepaired ventricular septal defects (VSDs) compared with age-matched, healthy infants. METHODS: Eight infants with VSDs and 10 healthy controls between 3 to 5 months of age participated in the study. Indirect calorimetry was used to measure REE and the doubly-labeled water method was used to measure TEE and energy intake. An echocardiogram and anthropometric measurements were performed on all study participants. Daily urine samples were collected at home for 7 days. Samples were analyzed by isotope ratio mass spectrometry. Data were compared using analysis of variance. RESULTS: No significant differences were found in REE (VSD, 42.2 +/- 8.7 kcal/kg/d; control, 43.9 +/- 14.1 kcal/kg/d) or energy intake (VSD, 90.8 +/- 19.9 kcal/kg/d; control, 87.1 +/- 11.7 kcal/kg/d) between the groups. The percent total body water was significantly higher in the VSD infants and the percent fat mass was significantly lower. TEE was 40% higher in the VSD group (VSD, 87.6 +/- 10.8 kcal/kg/d; control, 61.9 +/- 10.3 kcal/kg/d). The difference between TEE and REE, reflecting the energy of activity, was 2.5 times greater in the VSD group. CONCLUSIONS: REE and energy intake are virtually identical between the two groups. Despite this, infants with VSDs have substantially higher TEE than age-matched healthy infants. The large difference between TEE and REE in VSD infants suggests a substantially elevated energy cost of physical activity in these infants. These results demonstrate that, although infants with VSDs may match the energy intake of healthy infants, they are unable to meet their increased energy demands, resulting in growth retardation. 相似文献
28.
G Low GJ Irwin G Haddock SV Maroo 《Journal of Medical Imaging and Radiation Oncology》2006,50(3):249-251
The Currarino triad is a complex anomaly consisting of an anorectal malformation, a sacral bone defect and a presacral mass. It was first described in 1981 and since then, approximately 250 cases have been reported. Radiology has an important part to play in the diagnosis of this entity, as the imaging features are characteristic. We report a case of Currarino triad in an infant who presented with intractable constipation and discuss relevant MRI and plain radiography findings. 相似文献
29.
Loss of tumor-promoting activity of unleaded gasoline in N- nitrosodiethylamine-initiated ovariectomized B6C3F1 mouse liver 总被引:1,自引:0,他引:1
Unleaded gasoline (UG) vapor (2056 ppm) increased the incidence of liver
tumors in a chronic bioassay and exhibited tumor-promoting activity in
N-nitrosodiethylamine (DEN)-initiated female mouse liver. Estrogen
inhibited mouse liver tumor development and the hepatocarcinogenic and
tumor-promoting dose of UG produced uterine changes suggestive of estrogen
antagonism. To directly test the hypothesis that UG-induced tumor-promoting
ability is secondary to its interaction with the mouse liver tumor
inhibitor, estrogen, we compared the tumor-promoting ability of UG in
ovariectomized (Ovex) mice with the hepatic tumor-promoting ability of UG
in intact mice. Ovaries were surgically removed at 4 weeks of age. Exposure
to wholly vaporized UG (2018 ppm) under bioassay and tumor-promoting
conditions began at 8 weeks of age. After 4 months of exposure, UG
increased relative liver weight and hepatic microsomal cytochrome P450
pentoxyresourfin-O- dealkylase and ethoxyresorufin-O-deethylase activity to
a similar extent in intact and Ovex mice. Non-focal hepatocyte
proliferation, as measured by the incorporation of bromo-deoxyuridine, was
not changed by UG exposure and was similar in all treatment groups. After 4
months of exposure to DEN-initiated mice, UG significantly increased the
volume fraction of liver occupied by foci (three-fold) as compared to
control intact mice. As expected, volume of foci was elevated in
DEN/Ovex/control mice as compared to DEN/intact/control mice. In DEN/Ovex
mice UG did not significantly increase the focal volume fraction. Thus, the
tumor promoting activity of UG, as demonstrated by increased volume
fraction of liver occupied by hepatic foci in intact mice, is greatly
attenuated in Ovex mice. The volume fraction data in Ovex mice support the
hypothesis that the tumor promoting activity of UG is dependent upon the
interaction of UG with ovarian hormones. These data also indicate that
hepatic microsomal cytochrome P450 PROD and EROD induction, hepatomegaly
and non-focal hepatic LI are not specific markers of hepatic tumor
promoting activity of UG.
相似文献
30.
Zhang GJ; Tsuda H; Adachi I; Fukutomi T; Yamamoto H; Hirohashi S 《Japanese journal of clinical oncology》1997,27(6):371-377
Patients with primary breast carcinoma with one to three axillary lymph
node metastases but without distant metastases (n1-3) in Japan have been
shown to have a 10-year disease-free survival rate of > 60%. It would be
reasonable to divide n1-3 Japanese breast cancer patients into groups with
high- or low-risk for recurrence and to consider post-operative adjuvant
therapy. In the present study, we analyzed 228 consecutive Japanese
patients with n1-3 breast cancer who underwent radical mastectomy and were
followed up for a median time of 11.0 years. The expression of bcl-2, p53
and c-erbB-2 proteins in the primary tumors was examined
immunohistochemically and their prognostic roles were also analyzed along
with conventional clinicopathologic indicators. bcl-2 expression was
correlated with positive estrogen receptor status and inversely correlated
with p53, c-erbB-2 and histologic grade. Univariate analysis showed that
bcl-2, p53 and c-erbB-2 expression were prognostic indicators of the
patient's group as well as node status, histologic grade, tumor size, age
at diagnosis, menopausal status and estrogen receptor status. Cox's
regression analysis demonstrated that the number of nodes involved,
menopausal status, p53 and bcl-2 were independent predictors for overall
survival and that histologic grade and the number of nodes involved were
independent predictors for disease-free survival. These results suggest
that bcl-2 expression in combination with p53 and c-erbB-2 expression, the
number of lymph node metastases, histologic grade and menopausal status are
useful in selecting subgroups of n1-3 breast cancer patients with good or
poor prognoses.
相似文献