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1.
Ullenhag GJ Fagerberg J Strigård K Frödin JE Mellstedt H 《Cancer immunology, immunotherapy : CII》2004,53(4):331-337
A baculovirus-produced recombinant CEA (rCEA) protein comprising the extracellular region was used for vaccination of CRC patients with or without GM-CSF as an adjuvant cytokine. Ten patients with a significant proliferative T cell response against rCEA were selected for T cell epitope mapping. Fifteen-aa-long overlapping peptides covering the entire aa sequence of the external domain of CEA were used in a proliferation assay. In six of the patients a repeatable T cell response against at least one peptide was demonstrated. For the first time, nine functional HLA-DR epitopes of CEA were defined. Two of the peptides were recognized by more than one patient, i.e., two and three patients, respectively. Those 15-mer peptides that induced a proliferative T cell response fitted to the actual HLA-DR type (SYFPEITHI). The affinity of the native peptides for the T cell receptor was in the low to intermediate range (scores 6–19). The 15-mer peptides also contained 9-mer peptide sequences that could be predicted to bind to the actual HLA-ABC genotypes (SYFPEITHI/BIMAS). Blocking experiments using monoclonal antibodies indicated that the proliferative T cell response was both MHC class I and II restricted. The defined HLA-DR T cell epitopes were spread over the entire CEA molecule, but a higher frequency was noted towards the C-terminal. Peptides with a dual specificity may form a basis for production of subunit cancer vaccines, but modifications should be done to increase the T cell affinity, thereby optimizing the antitumoral effects of the vaccine.Abbreviations aa
amino acid
- CRC
colorectal carcinoma
- GM-CSF
granulocyte/monocyte colony stimulating factor
- CEA
carcino-embryonic antigen
- BCP
baculovirus control protein
- MHC
major histocompatibility complex
- pp
peptide
- TAA
tumor associated antigen 相似文献
2.
Tamer L Ercan B Ateş NA Değirmenci U Unlü A Ateş C Dirlik M Atik U 《Cell biochemistry and function》2006,24(2):131-135
The acetylation polymorphism is a common inherited variation in human drug and carcinogen metabolism. Because N- acetyltransferase (NAT2) is important for the detoxification and/or bioactivation of drugs and carcinogens, polymorphisms of this gene have important implications in therapeutics of and susceptibility to cancer. In this study, NAT2 genotype (NAT2*5A (C(481)T), NAT2*6A (G(590)A), NAT2*7A/B (G(857)A)) and NAT2*14A (G(191)A) and phenotype were determined in 125 patients with colorectal carcinoma and 82 healthy control in Mersin, a city located in the southern region of Turkey. Isolation of the subjects' DNA was performed by using a highly purified PCR template preparation kit/(Roche Diagnostics cat. no: 1 796 828) and the NAT2 polymorphism was detected using real-time PCR (Roche Diagnostics, GmbH, Mannheim, Germany). According to this study high protein intake is associated with the increased risk for the development of colon cancer (OR = 1.73; 95% CI, 1.10-3.07). Although only NAT2*14A fast type was associated with increased risk in patients with colorectal carcinoma (OR = 3.03; 95% CI, 1.56-5.86), when a high protein diet was considered, NAT2*7A/B fast genotype was also found to be associated with an increased risk (OR = 2.06, 95% CI for NAT2*7A/B, 1.10-3.86; OR = 2.65; 95% CI, 1.29-5.46 for NAT2*14A). Smoking status did not differ between the control and patient groups. Our data suggest that exposure to carcinogens through consumption of a high-protein diet may increase the risk of colorectal carcinoma only in genetically-susceptible individuals. 相似文献
3.
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
4.
Humoral anti-idiotypic and anti-anti-idiotypic immune response in cancer patients treated with monoclonal antibody 17-1A 总被引:4,自引:0,他引:4
Peter Ragnhammar Maria Liljefors Anna-Lena Hjelm Håkan Mellstedt Jan-Erik Frödin J. Fagersberg 《Cancer immunology, immunotherapy : CII》1996,42(2):81-87
A group of 96 patients with advanced colorectal carcinoma were treated with the mouse (m) or chimeric (c) (mouse variable
regions × human IgG1 constant regions) monoclonal antibody (mAb) 17-1A recognizing the tumour-associated antigen GA733-2.
Eighty-two of the 83 patients treated with mmAb17-1A and 69% of the patients given cmAb17-1A (n = 13) developed anti-idiotypic antibodies (ab2). Auto-antibodies binding to tumour cells expressing GA733-2 were found in 7% of the patients. In a further 38 patients (40%)
antitumour-cell antibodies, i.e. anti-anti-idiotypic antibodies (ab3), were induced by the mAb17-1A therapy. Patients with detectable ab3 after treatment had significantly higher ab2 levels than those not developing ab3. Addition of granulocyte/macrophage-colony-stimulating factor (GM-CSF) to mmAb17-1A significantly enhanced the induction
of ab2 as well as induction of anti-anti-idiotypic antibodies (ab3), compared to mmAb17-1A alone. Patients with a high increase in antitumour-cell antibodies (ab3) induced by the therapy lived significantly longer than patients with no or a low level of induction of ab3 (P = 0.016). The results indicate that induction of an idiotypic network response might be an important effector mechanism in
mAb therapy.
Received: 20 October 1995 / Accepted: 18 December 1995 相似文献
5.
A.-L. Hjelm Skog P. Ragnhammar J. Fagerberg J.-E. Frödin M. Goldinger H. Koldestam M. Liljefors B. Nilsson J. Shetye P. Wersäll H. Mellstedt 《Cancer immunology, immunotherapy : CII》1999,48(8):463-470
Granulocyte/macrophage-colony-stimulating factor (GM-CSF) has previously been indicated to enhance the therapeutic effect
of the anti-colorectal carcinoma mAb17-1A as well as to augment in vivo immune effector functions. In vitro interleukin-2
(IL-2) augmented GM-CSF-induced antibody-dependent cellular cytotoxicity, a mechanism considered to be of significance for
the therapeutic effect of mAb. A treatment regimen was elaborated that combined mAb17-1A (400 mg at day 3 of a 10-day treatment
cycle) with the simultaneous administration of GM-CSF (250 μmg/m2 once daily) and IL-2 (2.4 × 106 U/m2 twice daily) for 10 days. The treatment cycle was repeated once a month. Twenty patients with advanced colorectal carcinoma
were included in the study. One patient obtained a partial remission and 2 patients stable disease for 7 and 4 months respectively.
The median survival time from the start of mAb therapy was 8 months. Owing to allergic reactions, the planned mAb17-1A dose
had to be reduced by repeated infusions. At the fourth treatment cycle only 25% received the planned mAb dose. In 3 patients
the GM-CSF and IL-2 dose was reduced because of side-effects. The subjective tolerability of the treatment was considered
good or acceptable in more than 80% of the patients. The increment in white blood cell subsets induced by the cytokines decreased
by increasing number of courses. This particular regimen did not augment the therapeutic effect of mAb17-1A anticipated from
in vitro data but rather hampered the clinical effect of the antibody. The reason for this is not clear but a possibility
might be the induction of immune suppression in vivo resulting from an impaired human anti-(mouse Ab) and anti-idiotypic antibody
response as well as antibody-dependent cellular cytotoxicity, on the basis of a comparison of mAb17-1A/GM-CSF/IL-2- and mAb17-1A/GM-CSF-treated
patients.
Received: 25 February 1999 / Accepted: 15 July 1999 相似文献
6.
《Biomarkers》2013,18(3):216-222
The objective of this study was to clarify whether the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are significant prognostic markers in patients with resectable colorectal cancer (CRC). A total of 200 patients who underwent curative resection for CRC were enrolled. The NLR and PLR were positively correlated (p?<?0.001). Both the NLR and PLR were shown to be good prognostic biomarkers of overall survival (OS) (p?=?0.002 and p?=?0.001, respectively). The PLR was an independent prognostic factor of OS based on multivariate analysis (hazard ratio, 1.971; 95% confidence interval, 1.102–3.335; p?=?0.021). 相似文献
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8.
Jiankun Liu Yuzhong Duan Xiaoming Cheng Xi Chen Wei Xie Haixia Long Zhihua Lin Bo Zhu 《Biochemical and biophysical research communications》2011,407(2):160
IL-17, which exerts strong pro-inflammatory effects, has emerged as an important mediator in inflammation-associated cancer. However, the characteristics of IL-17-producing cells, the relevance of IL-17 to clinical parameters and its function in the development and progression of colorectal carcinoma still remain to be explored. In the present study, we first found the levels of IL-17 producing cells were significantly increased in the tumor regions of samples from colorectal carcinoma patients compared with non-tumor regions. Confocal microscopic analysis showed co-staining of IL-17 with CD4 and CD68, indicating IL-17 in colorectal carcinoma was expressed by macrophage and Th17. High expression of IL-17 was associated with high microvessel density. Univariate and multivariate analysis revealed that IL-17 was an independent prognostic factor for overall survival. To explore the underlying mechanisms of IL-17 in angiogenesis, we used PCR-array to find pro-angiogenic factor in cancer cells specifically induced by IL-17, then validated VEGF as one of factors in IL-17-mediated angiogenesis with the use of quantitative RT-PCR, ELISA and VEGF immunohistochemistry. Our results propose IL-17 as a novel indicator of prognosis in the patients with colorectal carcinoma and could serve as a novel therapeutic target for colorectal carcinoma, furthermore our results indicate that IL-17 producing cells may facilitate development of colorectal carcinoma by fostering angiogenesis via promote VEGF production from cancer cells. 相似文献
9.
用免疫组化技术和PCR-SSCP技术对高、中、低分化大肠腺癌、癌旁粘膜、正常粘膜及大肠腺癌型息肉的P21、P53蛋白表达和k-ras基因、P53基因突变进行检测。结果,大肠腺癌P21、P53蛋白表达比大肠腺瘤增多,但增加不显著(P〉0.05),二组均比癌旁粘膜和正常粘膜P21、P53蛋白表达阳性率高(P〈0.01),大肠腺癌k-ras基因和P53基因突变率比大肠腺瘤、癌旁粘膜和正常粘膜组显著增加 相似文献
10.
11.
Suppression of human selenium-binding protein 1 is a late event in colorectal carcinogenesis and is associated with poor survival 总被引:3,自引:0,他引:3
Kim H Kang HJ You KT Kim SH Lee KY Kim TI Kim C Song SY Kim HJ Lee C Kim H 《Proteomics》2006,6(11):3466-3476
The purpose of this study was to analyze altered protein expression in cancer tissues and determine its relationship to prognosis in colorectal carcinomas. We performed proteomic expression analysis on 14 colorectal carcinomas and matched nontumorous colonic mucosa by 2-DE and MALDI-TOF-MS. Comparative analysis of the respective spot patterns on 2-DE showed 14 spots that were markedly changed in the colorectal carcinomas. Among them, selenium-binding protein 1 (SELENBP1) was markedly decreased in 12 (85%) carcinomas. The reduced expression of SELENBP1 was further supported by Western blot analysis and immunohistochemistry. Suppression of SELENBP1 was further analyzed in another eight-paired adenomas and carcinomas from the same patients using Western blot analysis and immunohistochemistry, and revealed that one adenoma and seven carcinomas exhibited markedly reduced SELENBP1 expression. Patients with low levels of SELENBP1 expression had significantly lower overall survival rates (72 vs. 85%, p = 0.021) among the 240 stages II and III colorectal carcinomas by using tissue microarray analysis. Our findings indicate that suppression of SELENBP1 is a frequent and late event in colorectal carcinogenesis, and may contribute to the rapid progression of colorectal carcinoma. 相似文献
12.
Miodrag Joci Neboja Arsenijevi Nevena Gajovi Milena Jurievi Ivan Jovanovi Milan Jovanovi Nataa Zdravkovi Veljko Mari Marina Jovanovi 《Journal of Medical Biochemistry》2022,41(1):79
BackgroundPatients with colorectal cancer (CRC) have anemia often present as a consequence of chronic bleeding from tumor. The exact role of lL-33, Galectin-l and IL-l in the pathological genesis of anemia in colorectal cancer patients has not been elucidated yet. The main goal of this research was to analyze Gal-l, IL-l and lL-33 systemic values in anemic and non-anemic CRC patients.MethodsConcentrations of IL-33, Galectin-1 and IL-1 have been studied in blood samples of 55 CRC patients (27 without anemia and 28 with anemia).ResultsCRC patients with anemia had more severe and local advanced disease compared to CRC non-anemic patients. Anemia positively correlated with higher nuclear grade, lymph and blood vessel invasion, as well as with higher TNM stage, detectable metastatic lesions in lung and liver and peritoneal carcinomatosis. Significantly higher IL-33, Gal-1 and IL-1 concentration have been found in sera of patients with CRC and detected anemia. CRC patients mostly had microcytic anemia, while ferritin values were in normal range. Analysis revealed positive mutual correlation between serum values of galectin-1, IL-1 and IL-33 in CRC patients. Level of hemoglobin negatively correlated with serum IL-33, Gal-1 and IL-1. We have analyzed the Receiver Operating Characteristic (ROC) curves of serum IL-33, Gal-1 and IL-1 showed that these cytokines can be treated as additional markers for anemia of inflammation in CRC patients.ConclusionsPredomination of Galectin-1, IL-1 and IL-33 in anemic CRC patients implicates on their potential role in anemia genesis and further development. 相似文献
13.
Gabriella Gruden Patrizia Carucci Valentina Lolli Loretta Cosso Erika Dellavalle Emanuela Rolle Alessandro Cantamessa Silvia Pinach Maria Lorena Abate Donata Campra Franco Brunello Graziella Bruno Mario Rizzetto Paolo Cavallo Perin 《Cell stress & chaperones》2013,18(2):235-241
Levels of serum heat shock protein 27 (sHsp27) have been studied in numerous cancer types, but their potential relevance in patients with hepatocellular carcinoma (HCC) is undetermined. Our aim was to compare sHsp27 levels in patients with HCC and HCC-free controls. Specifically, we recruited 71 patients with HCC (80 % with early tumour), 80 patients with chronic liver disease (59 with liver cirrhosis and 21 with chronic active hepatitis) and 42 healthy subjects. sHsp27 was measured by immunoenzymatic assay. Results showed that sHsp27 levels were significantly (p < 0.001) higher in patients with HCC than in the other groups, particularly in those with hepatitis C virus (HCV)-related disease. In HCC patients, sHsp27 levels were not associated with prognostic risk factors, such as size/multiplicity of nodules and stage. In logistic regression analysis, performed in patients with liver disease, log-sHsp27 was associated with a significant age-adjusted 2.5-fold increased odds ratio of HCC and with a significant 4.4-fold higher odds ratio of HCC in the subgroup with HCV-related liver disease. In receiver operating characteristic curve analysis, sensitivity and specificity of the best sHsp27 cut-off value (456.5 pg/ml) for differentiating patients with HCC from those with HCC-free chronic liver disease were 70 and 73 %, respectively. In conclusion, sHsp27 levels are enhanced in patients with HCC and may represent a candidate biomarker of HCC. 相似文献
14.
Objective: To evaluate the clinical value of 18F-FDG PET/CT in postoperative monitoring for patients with colorectal carcinoma. Methods: 66 postoperative patients with colorectal carcinoma underwent whole-body FDG PET/CT. The final histopathological and formal clinical follow-up findings were used as gold standard to determine the sensitivity and specificity of FDG PET/CT and enhanced CT of the same periods. Results: The sensitivity and specificity of FDG PET/CT in detecting recurrence are 96.30%, 94.87% (while enhanced CT are 70.37% and 87.18% respectively). The sensitivity and specificity in detecting metastasis are 95.35%, 82.61% (enhanced CT are 61.90%, 75.00%). SUVmax was significantly higher in malignant lesions [range 4.16–22.00, mean ± standard deviation (x ± s) 8.06 ± 4.30] than in benign ones (range1.18–6.25, x ± s 2.82 ± 1.02). Conclusion: At present, whole-body 18F-FDG PET/CT is an advanced diagnostic imaging technique in detecting loco-regional recurrence and metastasis in postoperative patients with colorectal carcinoma for its higher sensitivity and specificity. 相似文献
15.
目的评价草酸铂(L-OHP)联合氟脲嘧啶(5-FU)、甲酰四氢叶酸钙(CF)二线治疗晚期复发大肠癌的疗效和不良反应。方法L-OHP 130 mg/m^2,静脉滴入,2 h,d1;CF 100 mg/m^2,5-FU前2小时静脉滴入,d1-d5;5-FU 500 mg/m^2,静脉滴入,6-8 h,d1-d5,21 d为1个周期。结果全组CR 1例,PR 3例,SD 17例,PD 4例,总有效率为16%,疾病控制率为84%。主要不良反应为中性粒细胞减少、消化道反应及外周神经毒性。结论L-OHP联合5-FU、CF方案(OFL)二线治疗晚期复发大肠癌安全、有效,毒性反应可耐受。 相似文献
16.
Expression of the membrane complement regulatory protein CD59 (protectin) is associated with reduced survival in colorectal cancer patients 总被引:1,自引:0,他引:1
Watson NF Durrant LG Madjd Z Ellis IO Scholefield JH Spendlove I 《Cancer immunology, immunotherapy : CII》2006,55(8):973-980
It has been known for some time that the immune system can recognise growing tumours, and that tumours may respond by modulation of molecules, which make them resistant to further attack. Expression, over-expression, or loss of these molecules may function as markers of tumour progression and prognosis. Among such molecules are the membrane-bound complement regulatory proteins (mCRP), which protect cells from bystander attack by autologous complement. These include CD59 (protectin), which prevents formation of the MAC complex in the terminal stages of complement activation. In the present study, we evaluated immunohistochemical expression of CD59 in a series of over 460 well-characterised colorectal cancers using tissue microarrays (TMA), and related this information to known tumour and patient variables and to survival. The CD59 expression was observed in 69 (15%) of cases overall, and was significantly associated with tumour grade. In contrast, no associations were noted with tumour site, stage or histological type. On survival analysis, a further correlation was observed between expression of CD59 by the colorectal tumours and a reduction in disease-specific patient survival. This observation was strongest for patients with early stage disease. However, a negative impact on survival was also seen in those patients with late stage disease. These results indicate that TMA linked to good clinicopathological databases with good long term follow up are useful tools for determining new prognostic indicators that can be used in future patient management. Immune surveillance may result in immune–editing that induces variable expression of a range of target antigens, and these may be useful prognostic markers. This study has identified CD59 expression as a marker of poor prognosis in colorectal cancer patients.This article is a symposium paper from the "Robert Baldwin Symposium: 50 years of Cancer Immunotherapy", held in Nottingham, Great Britain, on 30th June 2005. 相似文献
17.
Judit Kocsis Balázs Madaras Éva Katalin Tóth George Füst Zoltán Prohászka 《Cell stress & chaperones》2010,15(2):143-151
Many findings indicate that measuring the serum concentration of soluble 70-kD heat shock protein (soluble HSP70) may provide
important information in cardiovascular, inflammatory, and pregnancy-related diseases; however, only scarce data are available
in cancer. Therefore, using a commercial ELISA kit, we measured soluble HSP70 concentration in the sera of 179 patients with
colorectal cancer. We investigated the relationship between soluble HSP70 concentration and mortality, during 33.0 (24.4–44.0) months
long follow-up. High (>1.65 pg/ml, median concentration) soluble HSP70 level was a significant (hazard ratio: 1.88 (1.20–2.96,
p = 0.005) predictor of mortality during the follow-up period. When we compared the soluble HSP70 levels in patients with non-resected
primary tumors as compared to those who were recruited into the study 4–6 weeks after the tumor resection they were found
to be significantly (p = 0.020) higher in the former group. Since the patients with non-resected primary tumors had also distant metastasis and
died early, we limited the further analysis to 142 patients with no distant metastasis at the beginning of the follow-up.
This association remained significant even after multiple Cox-regression analysis had been performed to adjust the data for
age and sex (p = 0.028); age, sex, and TNM-T stage (p = 0.041); age, sex, and TNM-N stage (p = 0.021); age, sex, and histological grade (p = 0.023); or age, sex, and tumor localization (p = 0.029). Further analysis showed that the significant association between high HSP70 levels and poor survival is in the
strongest in the group of <70-year-old female patients (HR: 5.52 (2.02-15.15), p = 0.001), as well as in those who were in a less advanced stage of the disease at baseline. These novel findings indicate
that the serum level of soluble HSP70 might prove a useful, stage-independent prognostic marker in colorectal cancer without
distant metastasis. 相似文献
18.
Shinya Arinaga Nobuya Karimine Kiyoshi Takamuku Shigeru Nanbara Hiroshi Inoue Ryoji Abe Daisuke Watanabe Hideo Matsuoka Hiroaki Ueo Tsuyoshi Akiyoshi 《Cancer immunology, immunotherapy : CII》1992,35(4):246-250
Summary On the basis of our clinical findings that the ability of cancer patients to generate lymphokine-activated killer cells became markedly augmented after mitomycin C administration, we designed a treatment regimen comprising mitomycin C 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 700 U/m2 (8000 IU/kg), i.v. every 12 h from day 4 through day 8. The treatment course was repeated at almost 7-day intervals. Altogether 33 patients with advanced carcinoma, including mainly gastrointestinal carcinoma, were treated with this regimen. Of these, 10 had a partial response (PR) and 4 had a minor response (MR). Since eosinophil counts peaked 1 day after either the first or second course of the therapy, the posttreatment values were compared to each pretreatment level, with regard to the clinical antitumor response to this treatment. When patients who showed PR were defined as responders, absolute eosinophil counts and the percentages of eosinophils in responders after both the first and second courses of the therapy were significantly greater than each pretreatment value or the posttreatment level in nonresponders. Further, these findings were almost identical, when both PR and MR were considered to be a true remission and therefore patients who exhibited PR or MR were defined as responders, although the difference between posttreatment levels of eosinophils in responders and nonresponders was not significant at the second course. These results indicate that eosinophilia induced by this treatment correlates with the clinical response to this therapy. 相似文献
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20.
《DNA Repair》2016
PurposeThe aim of this study was to investigate polymorphisms in DNA repair genes as potential predictive factors among Chinese cervical cancer patients.MethodsA total of 72 patients with cervical carcinoma, who received cisplatin-based chemoradiotherapy and whose responses were evaluated by Response Evaluation Criteria in Solid Tumors, were included. The association between response to chemoradiotherapy and the genotypes for 29 single-nucleotide polymorphisms (SNPs) in 25 DNA repair genes were analyzed.ResultsA minor allele of SNP rs9350 in the exonuclease 1 gene was associated with a better response rate, regardless of age and tumor stage (odds ratio, 8.316; p = 0.002).ConclusionSNP rs9350 in the exonuclease 1 gene is involved in inter-individual differences in the response to cisplatin-based chemoradiotherapy, in patients with cervical carcinoma. 相似文献