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1.
Chan SY Gordon AN Coleman RE Hall JB Berger MS Sherman ML Eten CB Finkler NJ 《Cancer immunology, immunotherapy : CII》2003,52(4):243-248
The compound CMB-401 is an immunoconjugate consisting of the monoclonal antibody (MAb) hCTM01 directed against polymorphic epithelial mucin covalently bound to the cytotoxic antibiotic calicheamicin by an amide linker. We evaluated CMB-401 as monotherapy for the treatment of recurrent platinum-sensitive epithelial ovarian carcinoma (EOC). Twenty-one 21 women aged 38 to 80 years with recurrent EOC (recurrence >6 months after initial platinum-containing chemotherapy) were enrolled. Tumor response and serum cancer antigen 125 (CA125) levels were assessed before and after active treatment. After an initial intravenous (i.v.) dose of hCTM01 (without calicheamicin), the calicheamicin-linked CMB-401 (16 mg/m(2 ) i.v.) was administered over 60 min for up to 7 cycles, with 4 weeks between cycles. Nineteen patients were evaluable. Measurable changes observed following administration of CMB-401 did not meet the criteria for partial remission (PR). CMB-401 was not effective as monotherapy for this type of EOC. Adverse events experienced by patients in the study included nausea (95%), asthenia (90%), abdominal pain (62%), headache (57%), anorexia (57%), and diarrhea (57%), mostly at a toxicity grade level of 1 or 2. Based on published efficacy of conjugates that deliver calicheamicin via hybrid (bifunctional) linkers [e.g. gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia], we hypothesize that the amide linker used in CMB-401 may have contributed to its failure to induce PR in patients in this study. Use of hybrid linkers to target hCTM01 or other antibodies to EOC may warrant further investigation. 相似文献
2.
Petrarca C Casalino B von Mensdorff-Pouilly S Rughetti A Rahimi H Scambia G Hilgers J Frati L Nuti M 《Cancer immunology, immunotherapy : CII》1999,47(5):272-277
The humoral immune response against a tumour-associated antigen, polymorphic epithelial mucin (PEM, MUC1) in cancer patients
was studied by isolating specific B cells primed for the antigen. Human B lymphocytes from tumour-draining lymph nodes, obtained
from 12 patients with epithelial cancers, were immunoselected with magnetic beads coated with a 60mer synthetic peptide corresponding
to three tandem repeats of the protein core of the MUC1 antigen. Short-term cultures of B cells were established utilizing
interleukin-10 (IL-10), IL-4 and monoclonal antibody anti-CD40, and were maintained for a maximum of 3␣weeks. B cell culture
supernatants contained human anti-MUC1 antibodies, as detected by enzyme-linked immunosorbent assay, in 6/12 of the patients
tested. Five of these patients, all with early-stage cancer, also had high levels of circulating anti-MUC1 IgM antibodies
in the serum. A significant correlation was found (two-tailed P = 0.041) between the presence of circulating anti-MUC1 antibodies and the ability to isolate PEM-specific B cells from tumour-draining
lymph nodes. The technique proposed provides a useful method for the analysis of natural immunity against defined tumour antigens.
Received: 30 June 1998 / Accepted: 5 October 1998 相似文献
3.
Targeting of auxin carriers to the plasma membrane: differential effects of brefeldin A on the traffic of auxin uptake and efflux carriers 总被引:1,自引:1,他引:0
Monensin and brefeldin A (BFA), inhibitors of Golgi-mediated protein secretion, rapidly perturb the transport catalytic activity
of specific plasma membrane-associated efflux carriers for indole-3-acetic acid (IAA) and inhibit polar transport of IAA.
To determine if these responses result solely from perturbation of the efflux carrier or whether specific auxin uptake carrier
function is also affected, the influence of BFA on the cellular transport of a range of auxins with contrasting affinities
for specific auxin uptake and efflux carriers was investigated in zucchini (Cucurbita pepo L.) hypocotyl tissue. In-flight addition of BFA (3 · 10−5 mol · dm−3) caused a rapid (lag < 10 min) and substantial (fourfold) increase in the rate of [1-14C]IAA net uptake by zucchini hypocotyl tissue. In the presence of the specific auxin efflux carrier inhibitor N-1-naphthylphthalamic acid (NPA; 3 · 10−6 mol · dm−3), BFA slightly reduced the rate of [1-14C]IAA net uptake. Stimulation of [1-14C]IAA net uptake by BFA was concentration-dependent. In the absence of BFA, net uptake of [1-14C]IAA exhibited the characteristic biphasic response to increasing concentrations of competing cold IAA but in the presence
of BFA, [1-14C]IAA uptake decreased smoothly with increase in concentration of competing unlabelled IAA, indicating a loss of auxin efflux
carrier activity but retention of functional uptake carriers. The half-time for mediated efflux of [1-14C]IAA from preloaded zucchini tissue was substantially increased by BFA (t1/2 = 51 min, controls; 107 min, BFA-treated). Treatment with BFA and/or NPA did not significantly affect the net uptake by,
or efflux from, zucchini tissue of [1-14C]2,4-dichlorophenoxyacetic acid ([1-14C]2,4-D), a substrate for the auxin uptake carrier but not the auxin efflux carrier. Uptake of [1-14C]2,4-D declined smoothly with increasing concentrations of competing unlabelled IAA whether or not BFA was included in the
uptake medium, confirming the failure of BFA to perturb auxin uptake carrier function. Transport of 1-[4-3H]naphthaleneacetic acid (1-NAA) exhibited little response to BFA or NPA, confirming that it is only a weakly transported
substrate for the efflux carrier in zucchini cells.
Received: 12 November 1997 / Accepted: 27 January 1998 相似文献
4.
Renner C Hartmann F Jung W Deisting C Juwana M Pfreundschuh M 《Cancer immunology, immunotherapy : CII》2000,49(3):173-180
Fifteen patients with refractory Hodgkin's disease were treated in a dose-escalation trial with the bispecific monoclonal
antibody (bi-mAb) HRS-3/A9, which is directed against the Fcγ receptor III (CD16 antigen) and the Hodgkin's-associated CD30
antigen. Treatment consisted of four cycles of four bi-mAb infusions given over 1 h every 3–4 days at different dose levels
ranging from 1 mg/m2 to 64 mg/m2. Measurable serum levels (above 0.1 μg/ml) of circulating bi-mAb could be detected in patients treated with doses above 4 mg/m2, reaching peak levels of 9.5 μg/ml immediately after the end of antibody infusion on the highest dose level. Bi-mAb elimination
corresponded to second-order kinetics with a terminal half-life time (t
1/2,β) of 28–32 h. Bi-mAb treatment induced the occurrence of human anti-(mouse Ig) antibodies (HAMA) in 6 out of 13 patients initially
testing negative. All 6 patients not only developed anti-isotypic anti-(mouse Ig) but also anti-idiotypic and anti-anti-idiotypic
antibodies. While no consistent changes of peripheral blood cell counts, or of any lymphocyte subpopulation including natural
killer (NK) cells, has been observed, 4 out of 6 evaluable patients treated with doses of at least 4 mg/m2 showed an increase of NK cell activity within 2 weeks after treatment, which lasted for a maximum of 12 weeks. Circulating
amounts of soluble CD30 antigen could be detected in the serum of 6 patients. However, like the results and time courses of
all the other immunological parameters evaluated, this was not predictive for treatment outcome.
Received: 16 September 1999 / Accepted: 6 January 2000 相似文献
5.
Joseph J. Hendricks John D. Aber Knute J. Nadelhoffer Richard D. Hallett 《Ecosystems》2000,3(1):57-69
Nitrogen controls on fine root substrate quality (that is, nitrogen and carbon-fraction concentrations) were assessed using
nitrogen availability gradients in the Harvard Forest chronic nitrogen addition plots, University of Wisconsin Arboretum,
Blackhawk Island, Wisconsin, and New England spruce-fir transect. The 27 study sites encompassed within these four areas collectively
represented a wide range of nitrogen availability (both quantity and form), soil types, species composition, aboveground net
primary production, and climatic regimes. Changes in fine root substrate quality among sites were most frequently and strongly
correlated with nitrate availability. For the combined data set, fine root nitrogen concentration increased (adjusted R
2 = 0.46, P < 0.0001) with increasing site nitrate availability. Fine root “extractive” carbon-fraction concentrations decreased (adjusted
R
2 = 0.32, P < 0.0002), “acid-soluble” compounds increased (adjusted R
2 = 0.35, P < 0.0001), and the “acid-insoluble” carbon fraction remained relatively high and stable (combined mean of 48.7 ± 3.1% for
all sites) with increasing nitrate availability. Consequently, the ratio of acid-insoluble C–total N decreased (adjusted R
2 = 0.40, P < 0.0001) along gradients of increasing nitrate availability. The coefficients of determination for significant linear regressions
between site nitrate availability and fine root nitrogen and carbon-fraction concentrations were generally higher for sites
within each of the four study areas. Within individual study sites, tissue substrate quality varied between roots in different
soil horizons and between roots of different size classes. However, the temporal variation of fine root substrate quality
indices within specific horizons was relatively low. The results of this study indicate that fine root substrate quality increases
with increasing nitrogen availability and thus supports the substrate quality component of a hypothesized conceptual model
of nitrogen controls on fine root dynamics that maintains that fine root production, mortality, substrate quality, and decomposition
increase with nitrogen availability in forest ecosystems in a manner that is analogous to foliage. 相似文献
6.
Behaviour of interleukin-2 serum levels in advanced non-small-cell lung cancer patients: relationship with response to therapy and survival 总被引:8,自引:0,他引:8
Orditura M Romano C De Vita F Galizia G Lieto E Infusino S De Cataldis G Catalano G 《Cancer immunology, immunotherapy : CII》2000,49(10):530-536
Interleukin(IL)-2 is a T helper (Th) 1 type cytokine that has been shown to play an important role in antitumour immune responses.
In this study, the prognostic significance of serum IL-2 levels was investigated in 60 advanced non-small-cell lung cancer
(NSCLC) patients. IL-2 serum levels were determined before chemotherapy, at the end of chemotherapy and during follow-up,
using a commercially available enzyme-linked immunoadsorbent assay kit. The results were analysed according to the response
to therapy and were used to generate a model predicting overall survival and time to treatment failure. All 60 patients were
shown to have higher IL-2 serum levels than controls (P < 0.0001). Stage IV patients had significantly lower IL-2 levels than stage III patients (P < 0.0001), although they were still significantly higher than controls (P < 0.0001). It is interesting that, when patients were divided into responders and non-responders according to the response
to therapy, the former were shown to have significantly higher pre-chemotherapy levels than the latter (P < 0.0001). Moreover, a further significant increase in IL-2 serum levels (P=0.004) and a significant decrease (P < 0.0001) were shown in responders and non-responders, respectively at the end of the therapy. Using univariate and multivariate
analyses, both overall survival and time to treatment failure were shown to be affected by the mean pathological levels of
IL-2. Furthermore, the prognostic significance of the serum level of IL-2 was confirmed by the stepwise regression analysis.
In conclusion, determination of pre-treatment IL-2 serum levels was shown to be of independent prognostic utility in patients
with advanced NSCLC; therefore, its possible use for prediction of outcome is proposed.
Received: 16 March 2000 / Accepted: 27 July 2000 相似文献
7.
Ole Rintek Madsen Ulrik Birk Lauridsen Andreas Hartkopp Ole Helmer S?rensen 《European journal of applied physiology and occupational physiology》1997,75(3):239-245
Dual energy x-ray absorptiometry (DEXA) offers the possibility of assessing regional soft tissue composition, i.e. lean mass (LM) and fat
mass : LM may be considered a measure of muscle mass. We examined age-related differences in LM, percentage fat (%fat) and
muscle strength in 100 healthy non-athletic women aged 18–87 years. Relationships between muscle strength and leg LM in 20
elite female weight lifters and in 18 inactive women with previous hip fractures were also studied. The LM and %fat of the
whole body, trunk, arms and legs were derived from a whole body DEXA scan. Isokinetic knee extensor strength (KES) and flexor
strength (KFS) at 30° · s–1 were assessed using an isokinetic dynamometer. The women aged 71–87 years had 35% lower KES and KFS than the women aged 18–40
years (P < 0.0001). Differences in LM were less pronounced. The LM of the legs, for instance, was 15% lower in the old than in the
young women (P < 0.0001). In a multiple regression analysis with age, body mass, height and leg LM or KES as independent variables and KES
or leg LM as the dependent variable, age was the most important predictor of KES (r
partial = −0.74, P < 0.0001). The same applied to KFS. Body mass, not age, was the most important predictor of leg LM (r
partial = 0.65, P < 0.0001) and of LM at all other measurement sites. The LM measured at different regions decreased equally with increasing
age. The KES:leg LM ratio was negatively correlated with age (r = −0.70, P < 0.0001). The weight lifters had significantly higher KES:leg LM ratios than age-matched controls (+12%, P < 0.0001) and vice versa for the women with previous hip fractures (–36%, P < 0.0001). In conclusion, from our study it would seem that in healthy nonathletic women, age is a more important determinant
of muscle strength than is LM as measured by DEXA. Muscle strengthening exercises and inactivity seem to have a considerably
stronger influence on muscle strength than on LM.
Accepted: 27 August 1996 相似文献
8.
Intracellular cytokine profile of T cells from children with acute lymphoblastic leukemia 总被引:12,自引:0,他引:12
Zhang XL Komada Y Chipeta J Li QS Inaba H Azuma E Yamamoto H Sakurai M 《Cancer immunology, immunotherapy : CII》2000,49(3):165-172
Purpose: During an ongoing immune response, cytokines produced by T helper types 1 (Th1) and 2 (Th2) together with T cytotoxic types
1 (Tc1) and 2 (Tc2) are critical to the effectiveness of that response. Dysregulated expansion of one or the other subset
may contribute to the impaired function of the T-cell-mediated immune system in cancer patients. In the present study we have
investigated whether such dysregulation might exist in children with acute lymphoblastic leukemia (ALL). Methods: We analyzed 61 blood samples from 45 children with B cell precursor ALL and 16 healthy children. Interleukin(IL)-2, IL-4,
and interferon γ (IFNγ) production of their respective purified CD4+ and CD8+ T cells were assessed at the single-cell level by intracellular-cytokine-staining flow cytometry. Results: At the time of diagnosis, IL-2-producing cell populations in CD4+ and CD8+ T cells were reduced below the normal range in 31 of 44 (70.5%) and 23 of 38 (60.5%) cases respectively. Similarly, IFNγ-producing
cell populations in CD4+ and CD8+ T cells decreased in 17 of 44 (38.6%) and 18 of 38 (47.4%) cases respectively. Conversely cell populations capable of IL-4
production in CD4+ and CD8+ T cell subsets were increased in 13 of 30 (43.3%) and 15 of 30 (50.0%) cases respectively. Therefore, the Th1-to-Th2 and
Tc1-to-Tc2 ratios (1.6 ± 2.2 and 7.7 ± 6.7 respectively) were significantly lower in peripheral blood T cells of ALL patients
(n = 30) than those (6.0 ± 2.9 and 20.1 ± 10.3 respectively) in 15 healthy controls (P < 0.0001). Although both CD45RA+/CD4+ and CD45RA+/CD8+ cells significantly increased in 43 ALL patients (P < 0.05), there existed no apparent correlation between CD45 isoform expression and cytokine (IL-2 and IFNγ) production. Interestingly,
the ability to produce both IL-2 and IFNγ was recovered in 8 cases examined, after complete remission had been achieved. Conclusion: These observations suggest that, in both CD4+ and CD8+ T cells of ALL patients, there is a dysregulation in the functionality of Th1 (Tc1) and Th2 (Tc2) cells with a gross reduction
of Th1 (Tc1) cell populations and an expansion in Th2 (Tc2).
Received: 12 November 1999 / Accepted: 2 January 2000 相似文献
9.
Roovers RC van der Linden E de Bruïne AP Arends JW Hoogenboom HR 《Cancer immunology, immunotherapy : CII》2001,50(1):51-59
Antibodies to tumour-associated antigens are increasingly being used as targeting vehicles for the visualisation and for
therapy of human solid tumours. The epithelial cell adhesion molecule (Ep-CAM) is an antigen that is overexpressed on a variety
of human solid tumours and constitutes an attractive target for immunotargeting. We set out to obtain fully human antibodies
to this antigen by selecting from a large antibody repertoire displayed on bacteriophages. Two single-chain variable antibody
fragments (scFv) were identified that specifically bound recombinant antigen in vitro. One of the selected antibodies (VEL-1)
cross-reacted with extracellular matrix components in immunohistochemistry of colon carcinoma, whereas the other scFv (VEL-2)
specifically recognised colon cancer cells. The latter antibody was further characterised with respect to epitope specificity
and kinetics of antigen-binding. It showed no competition with the well-characterised anti Ep-CAM MOC-31 monoclonal antibody
and had an off-rate of 5 × 10−2 s−1. To obtain an antibody format more suitable for in vivo tumour targeting and to increase the apparent affinity through avidity,
the genes of scFv VEL-2 were re-formatted by fusion to a human (γ1) hinge region and CH3 domain. This “minibody” was expressed
in Escherichia coli, specifically bound the Ep-CAM antigen and showed a 20-fold reduced off-rate in surface plasmon resonance analysis. These
results show that phage antibody selection, combined with antibody engineering, may result in fully human antibody molecules
with promising characteristics for in vivo use in tumour targeting.
Received: 13 July 2000 / Accepted: 12 October 2000 相似文献
10.
Long-term treatment with low doses of interleukin-2 and interferon-α: immunological effects in advanced renal cell cancer 总被引:2,自引:0,他引:2
Pavone L Andrulli S Santi R Majori M Buzio C 《Cancer immunology, immunotherapy : CII》2001,50(2):82-86
We aimed to determine the immunological effects of low doses of recombinant interleukin-2 (rIL-2) and recombinant interferon-α
(rIFN-α) in patients bearing advanced renal cell carcinoma.
Methods: Twenty-seven patients received therapeutic cycles consisting of subcutaneous rIL-2 for 5 days per week and intramuscular
rIFN-α twice weekly, for 4 consecutive weeks. The cycle was repeated indefinitely at regular 4-month intervals, for all patients.
rIL-2 (1 × 106 IU/m2) was administered every 12 h on days 1 and 2 and once a day on days 3–5 of each week; rIFN-α (1.8 × 106 IU/m2) was given on days 3 and 5.
In the enrolled patients, total and differential white blood cell counts, phenotypic analysis of some lymphocyte subsets,
and soluble IL-2 receptor (sIL-2R), were investigated before and after each of the first six cycles of therapy (about 24 months
of follow-up).
Results: The cycles of immunotherapy induced a significant increase of total lymphocytes (37%, P < 0.001), eosinophils (222%, P < 0.001), CD25+ cells (27%, P=0.004), sIL-2R (174%, P < 0.001) and natural killer (NK) cells (CD3-CD56+) (61%, P < 0.001); the subset that expresses CD56 with high density (CD56+ bright) expanded more (233%, P < 0.001) than the subset expressing the same marker with low density (CD56+ dimmer) (15%, P=0.043). Unlike the previous subsets, the treatment decreased significantly T-lymphocytes with NK cell marker (CD3+ CD56+)
(28%, P=0.011).
No significant differences of effectiveness were found among the subsequent treatment cycles, except for CD25+ cells and sIL-2R
(P=0.036 and P=0.005, respectively): the increase induced by immunotherapy was maximum after the first cycle and decreased progressively
thereafter.
Conclusions: Long-term repeated cycles of low-dose immunotherapy induced repeated and significant expansion of one of the most important
lymphocyte subsets for the non-MHC-restricted immune response to the tumour mass: CD3–CD56+ cells.
Received: 8 November 2000 / Accepted: 11 January 2001 相似文献
11.
Watanabe A Shimokawa T Moriyama M Komine F Amaki S Arakawa Y Ra C 《Immunogenetics》2006,58(12):937-946
Fc receptor for IgA (FcαR, CD89) is capable of triggering IgA-mediated immune responses to pathogens and has been proposed to function in circulating IgA clearance. Because inheritable variations modifying individual immune responses or immunoglobulin catabolism may affect the chronicity of viral infection, we investigated whether promoter polymorphisms of the FcαR gene (FCAR) affect chronic hepatitis C virus (HCV) infection and its disease progression. The two −311T/C and −142T/C single-nucleotide polymorphisms (SNPs) were studied by direct DNA sequencing in 177 Japanese patients with chronic hepatitis C (CHC). Both −311CC and −142CC genotypes were more frequent in CHC patients (15.9 and 18.6%) compared with 210 healthy controls (5.7 and 10.0%) [p = 0.001, odds ratio (OR) = 3.10, 95% confidence interval CI) = 1.53–6.30 and p = 0.014, OR = 2.06, 95% CI = 1.14–3.72, respectively], and were associated with infection with HCV genotype 2a/2b (p = 0.019 and p = 0.005, respectively). Conversely, −311CC and −142CC were decreased in 59 patients at advanced stages of disease as assessed on the basis of hepatic fibrosis markers such as decreased platelet count (PLT) ( < 150,000/μl) (5.1 and 8.5%) compared with 91 patients with normal PLT ( ≥ 150,000/μl) (24.2 and 26.4%) (p = 0.006 and p = 0.005, respectively). Moreover, among the patients with normal PLT (but not with decreased PLT), −311CC or −142CC was significantly associated with decreased serum IgA levels (p = 0.023 or p = 0.007, respectively). These results suggest that the FCAR promoter SNPs may be related to chronic HCV infection and disease progression in Japanese CHC, which might be explained by altered FcαR expression affecting IgA-mediated immune responses and/or IgA catabolism. 相似文献
12.
Holcombe RF Jacobson J Dakhil SR Stewart RM Betzing KS Kannan K Macdonald JS 《Cancer immunology, immunotherapy : CII》1999,48(9):533-539
Levamisole (LMS), utilized in the adjuvant treatment of patients with stage III colon cancer, is immunomodulatory. To determine
whether alterations in immune parameters before, during and after 12 months of 5FU/LMS therapy correlate with disease-free
survival, 38 patients enrolled on Southwest Oncology Group (SWOG) protocol 8899 received extensive lymphocyte phenotypic analysis
prior to therapy and 3, 6, 12 and 15 months after treatment initiation. The median follow-up of patients is 41 months. Significant
increases in the proportion and total number of CD56+ natural killer cells were seen, starting at 3 months and continuing until 15 months (P < 0.001). Increases in the total numbers of cells expressing CD25 (interleukin-2 receptor), VLA4 and the combinations of CD4:
CD45RA and CD4:CDw29 were not evident during therapy but were seen at 15 months (P < 0.05: CD25, CD4:CDw29, CD4:CD45RA; P < 0.001: VLA4). Low levels of CD8+ cells prior to treatment initiation and after 3 months of therapy correlated with early relapse within the first year of
5FU/LMS treatment. Patients who have remained disease-free (n = 22, median follow-up 45 months) demonstrated increases in the total numbers of CD8+, CD25+, CD56+, VLA4+, CD4: CDw29 and CD4:CD45RA cells, primarily at 15 months. In contrast, patients who relapsed had decreased numbers of CD8+, CD4:CDw29, CD4: CD45RA and VLA4+ cells and minimal increases in CD56+ and CD25+ cells. Statistically significant differences between the late-relapse group and the group remaining disease-free were seen
for CD25+, CD4: CD45RA and CD4:CDw29 cells at the 15-month assay time (P = 0.0276, P = 0.0349, P = 0.0178 respectively). In conclusion, multiple alterations in lymphocyte phenotype, with increases in the proportion and total
number of cells involved in cell-mediated immune responses, were seen during and especially following completion of therapy
with 5FU/LMS. Many of these changes are significantly associated with clinical outcome and may be useful for risk stratification
of stage III colon cancer patients following completion of adjuvant therapy.
Received: 9 July 1999 / Accepted: 11 August 1999 相似文献
13.
Autoantibodies against the tumour-associated antigen GA733-2 in patients with colorectal carcinoma 总被引:2,自引:0,他引:2
Mosolits S Harmenberg U Rudén U Ohman L Nilsson B Wahren B Fagerberg J Mellstedt H 《Cancer immunology, immunotherapy : CII》1999,47(6):315-320
The tumour-associated antigen (TAA) GA733-2 is expressed as a non-secreted surface molecule on the majority of human colorectal
carcinoma cells. The antigen has been used as a target for passive and active immunotherapy during the last decade. To determine
the incidence of autoantibodies against this antigen, sera from 1068 patients with colorectal carcinoma were analysed for
naturally occurring IgG antibodies against the baculovirus-produced GA733-2E protein. A total of 14.5% of the patients had
IgG antibodies against the antigen. In 519 patients, sera were collected at the time of diagnosis and 15% of those patients
had anti-GA733-2E IgG antibodies. There was a tendency to a higher frequency of patients with antibodies among those in the
advanced Dukes stages: 11% in stage A and 32% in stage D respectively (P = 0.06). Antibodies could be detected for up to 10 years after the diagnosis. Patients with Crohn's disease or colitis ulcerosa
(n = 20) did not elicit anti-GA733-2E antibodies. No healthy control donor (n = 45) had detectable antibodies against the antigen. The specificity of GA733-2E-reactive serum IgG was indicated by significant
inhibition of mAb17-1A (originally used to define GA733-2) binding to the GA733-2E antigen. Sera of positive patients bound
to the GA733-2-expressing human colorectal carcinoma cell line, SW948. No significant correlation was found between the presence
of antibodies and survival in the present patient population. However, the high incidence of autoantibodies against this tumour
antigen in colorectal carcinoma patients confirms its antigenicity in humans and supports the use of the GA733-2 antigen as
a target for immunotherapy.
Received: 25 May 1998 / Accepted: 26 November 1998 相似文献
14.
The purpose of this research was to use inline real-time near-infrared (NIR) to measure the moisture content of granules manufactured
using a commercial production scale continuous twin-screw granulator fluid-bed dryer milling process. A central composite
response surface statistical design was used to study the effect of inlet air temperature and dew point on granule moisture
content. The NIR moisture content was compared to Karl Fischer (KF) and loss on drying (LOD) moisture determinations. Using
multivariate analysis, the data showed a statistically significant correlation between the conventional methods and NIR. The
R
2 values for predicted moisture content by NIR versus KF and predicted moisture values by NIR versus LOD were 0.94 (p < 0.00001) and 0.85 (p < 0.0002), respectively. The adjusted R
2 for KF versus LOD correlation was 0.85 (p < 0.0001). Analysis of the response surface design data showed that inlet air temperature over a range of 35–55°C had a significant
linear impact on granule moisture content as measured by predicted NIR (adjusted R
2 = 0.84, p < 0.02), KF (adjusted R
2 = 0.91, p < 0.0001), and LOD (adjusted R
2 = 0.85, p < 0.0006). The inlet air dew point range of 10–20°C did not have a significant impact on any of the moisture measurements. 相似文献
15.
Ozkaya M Sahin M Cakal E Gisi K Bilge F Kilinc M 《Biological trace element research》2009,128(2):144-151
The present study was conducted to evaluate the serum selenium levels in first-degree relatives of diabetic patients (FDR)
according to controls. Insulin resistance, serum lipid levels, inflammation markers, and blood pressure were also studied
in these patients. Serum levels of selenium in FDR were significantly lower than control group (74.65 ± 5.9 vs 88.7 ± 8.7 μg/dl,
p < 0.0001). HsCRP, HOMA-IR, insulin, homocysteine levels were significantly higher in FDR according to the control group (1.32 ± 0.9
vs 0.63 ± 0.4 mg/dL, p < 0.0001; 2.07 ± 0.84 vs 1.51 ± 0.69, p < 0.0001; 9.26 ± 3.8 vs 6.8 ± 2.98 μU/MI, p < 0.0001; 15.7 ± 7.4 vs 11.5 ± 5.1 μmol/L, p < 0.0001, respectively). There was significant correlation between selenium levels and hsCRP (r = − 0.450, p < 0.0001). There was also weak significant correlation also between HOMA-IR and selenium levels (r = −0.227, p = 0.003). There was a correlation between systolic blood pressure and BMI (r = 0.365, p < 0.0001). But there was no correlation between selenium levels and blood pressure or other parameters. HsCRP, HOMA-IR, homocysteine
levels in individuals with selenium levels < 80 μg/L (n = 78) was significantly higher than hsCRP HOMA-IR, homocysteine levels in individuals with selenium levels ≥ 80 (n = 91; 1.23 ± 0.98 vs 0.81 ± 0.76 mg/dL, p < 0.003; 1.99 ± 0.88 vs 1.64 ± 0.74, p < 0.005; 15.0 ± 7.6 vs 12.9 ± 5.7 μmol/L, p < 0.049, respectively). Selenium deficiency may contribute to cardiovascular disease risk in FDR. 相似文献
16.
James Nelson Jeffrey Chanton Felicia Coleman Christopher Koenig 《Environmental Biology of Fishes》2011,90(3):243-252
To determine the feasibility of using stable isotopes to track diet shifts in wild gag, Mycteroperca microlepis, populations over seasonal timescales, we conducted a repeated measures diet-shift experiment on four adult gag held in the
laboratory. Fish were initially fed a diet of Atlantic mackerel, Scomber scombrus, (mean δ13C = −21.3‰ ± 0.2, n = 20) for a period of 56 days and then shifted to a diet of pinfish, Lagodon rhomboids, (mean δ13C = −16.6‰ ± 0.6, n = 20) for the 256 day experiment. We developed a non-lethal surgical procedure to obtain biopsies of the muscle, liver, and
gonad tissue monthly from the same four fish. We then determined the δ13C value of each tissue by isotope ratio mass spectrometry. For the gonad tissue we used the relationship between C/N and lipid
content to correct for the influence of lipids on δ13C value. We observed a significant shift in the δ13C values of all of the tissues sampled in the study. Carbon turnover rates varied among the three tissues, but the shift in
diet from mackerel to pinfish was clearly traceable through analysis of δ13C values. The turnover rates for muscle tissue were 0.005‰ day−1, and for gonad tissue was 0.009‰ day−1. Although it is generally thought that tissue turnover rates in ectotherms are driven primarily by growth, we found that
metabolic rate can be a major factor driving tissue turnover in adult gag. 相似文献
17.
Kabir ME Krishnaswamy S Miyamoto M Furuichi Y Komiyama T 《Applied microbiology and biotechnology》2011,90(2):553-564
Phage-display and competitive panning elution leads to the identification of minimum-sized antigen binders together with conventional
antibodies from a mouse cDNA library constructed from HM-1 killer toxin neutralizing monoclonal antibody (nmAb-KT). Antigen-specific
altered camelid-like single-domain heavy chain antibody (scFv K2) and a conventional antibody (scFv K1) have been isolated
against the idiotypic antigen nmAb-KT. The objectives of the study were to examine (1) their properties as compared to conventional
antibodies and also (2) their antifungal activity against different pathogenic and non-pathogenic fungal species. The alternative
small antigen-binder, i.e., the single-domain heavy chain antibody, was originated from a conventional mouse scFv phage library
through somatic hyper-mutation while selection against antigen. This single-domain antibody fragment was well expressed in
bacteria and specifically bound with the idiotypic antigen nmAb-KT and had a high stability and solubility. Experimental data
showed that the binding affinity for this single-domain antibody was 272-fold higher (K
d = 1.07 × 10−10 M) and antifungal activity was three- to fivefold more efficient (IC50 = 0.46 × 10−6 to 1.17 × 10−6 M) than that for the conventional antibody (K
d = 2.91 × 10−8 M and IC50 = 2.14 × 10−6 to 3.78 × 10−6 M). The derived single-domain antibody might be an ideal scaffold for anti-idiotypic antibody therapy and the development
of smaller peptides or peptide mimetic drugs due to their less complex antigen-binding site. We expect that such single-domain
synthetic antibodies will find their way into a number of biotechnological or medical applications. 相似文献
18.
Hörig H Lee DS Conkright W Divito J Hasson H LaMare M Rivera A Park D Tine J Guito K Tsang KW Schlom J Kaufman HL 《Cancer immunology, immunotherapy : CII》2000,49(9):504-514
The generation of cytotoxic effector T cells requires delivery of two signals, one derived from a specific antigenic epitope
and one from a costimulatory molecule. A phase I clinical trial was conducted with a non-replicating canarypoxvirus (ALVAC)
constructed to express both human carcinoembryonic antigen (CEA) and the B7.1 costimulatory molecule. This was the first study
in cancer patients to determine if the delivery of costimulation with a tumor vaccine was feasible and improved immune responses.
Three cohorts of six patients, each with advanced CEA-expressing adenocarcinomas, were treated with increasing doses of an
ALVAC-CEA-B7.1 vaccine (4.5 × 106, 4.5 × 107, and 4.5 × 108 plaque-forming units, PFU). Patients were vaccinated by intramuscular injection every 4 weeks for 3 months and monitored
for side-effects, tumor growth and anti-CEA immune responses. ALVAC-CEA- B7.1 at doses up to 4.5 × 108 PFU was given without evidence of significant toxicity or autoimmune reactions. Three patients experienced clinically stable
disease that correlated with increasing CEA-specific precursor T cells, as shown by in vitro interferon-γ enzyme-linked immunoassay
spot tests (ELISPOT). These three patients underwent repeated vaccination resulting in augmented CEA-specific T cell responses.
This study represents the first use of costimulation to enhance antitumor vaccines in cancer patients. This approach resulted
in CEA-specific immunity associated with stable diseases in three patients. This study also demonstrated that CEA-specific
T cell responses could be sustained by repeated vaccinations. Although the number of patients was small, the addition of B7.1
to virus-based vaccines may improve immunological and stable diseases to vaccination against tumor-associated antigens with
tolerable toxicity.
Received: 6 May 2000 / Accepted: 13 July 2000 相似文献
19.
Chintana Phawong Collins Ouma Piyatida Tangteerawatana Jarinee Thongshoob Tom Were Yuvadee Mahakunkijcharoen Duangrurdee Wattanasirichaigoon Douglas Jay Perkins Srisin Khusmith 《Immunogenetics》2010,62(6):345-356
Polymorphic variability in immune response genes, such as IL12B, encoding the IL-12p40 subunit is associated with susceptibility to severe malaria in African populations. Since the role
of genetic variation in conditioning severe malaria in Thai adults is largely unexplored, the functional association between
IL12B polymorphisms [i.e. IL12Bpro (rs17860508) and IL12B 3′ UTR T/G (rs3212227)], severe malaria and cytokine production was examined in patients with Plasmodium falciparum infections (n = 355) recruited from malaria endemic areas along the Thai–Myanmar border in northwest Thailand. Circulating IL-12p40 (p = 0.049) and IFN-γ (p = 0.051) were elevated in patients with severe malaria, while only IL-12p40 was significantly higher in severe malaria patients
with hyperparasitaemia (p = 0.046). Carriage of the IL12Bpro1.1 genotype was associated with enhanced severity of malaria (OR, 2.34; 95% CI, 0.94–5.81; p = 0.066) and hyperparasitaemia (OR, 3.42; 95% CI, 1.17–9.87; p = 0.025) relative to the IL12Bpro2.2 genotype (wild type). Individuals with the IL12Bpro1.1 genotype also had the lowest IL-12p40 (p = 0.002) and the highest IFN-γ (p = 0.004) levels. Construction of haplotypes revealed that carriage of the IL12Bpro-2/3′ UTR-T haplotype was associated with protection against severe malaria (OR, 0.51; 95% CI, 0.29–0.90; p = 0.020) and reduced circulating IFN-γ (p = 0.06). Thus, genotypic and haplotypic variation at IL12Bpro and IL12B 3′ UTR in this population influences susceptibility to severe malaria and functional changes in circulating IL-12p40 and
IFN-γ levels. Results presented here suggest that protection against severe malaria in Thai adults is associated with genotypic
variants that condition enhanced IL-12p40 and reduced IFN-γ levels. 相似文献
20.
Ten accessions belonging to the Brassica oleracea subspecies alba and rubra, and to B. oleracea var. sabauda were used in this study. Protoplasts were isolated from leaves and hypocotyls of in vitro grown plants. The influence of selected factors on the yield, viability, and mitotic activity of protoplasts immobilized
in calcium alginate layers was investigated. The efficiency of protoplast isolation from hypocotyls was lower (0.7 ± 0.1 × 106 ml−1) than for protoplasts isolated from leaf mesophyll tissue (2 ± 0.1 × 106 ml−1). High (70–90%) viabilities of immobilized protoplasts were recorded, independent of the explant sources. The highest proportion
of protoplasts undergoing divisions was noted for cv. Reball F1, both from mesophyll (29.8 ± 2.2%) and hypocotyl (17.5 ± 0.3%)
tissues. Developed colonies of callus tissue were subjected to regeneration and as a result plants from six accessions were
obtained. 相似文献