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991.
Fischer K Hoffmann P Voelkl S Meidenbauer N Ammer J Edinger M Gottfried E Schwarz S Rothe G Hoves S Renner K Timischl B Mackensen A Kunz-Schughart L Andreesen R Krause SW Kreutz M 《Blood》2007,109(9):3812-3819
A characteristic feature of tumors is high production of lactic acid due to enhanced glycolysis. Here, we show a positive correlation between lactate serum levels and tumor burden in cancer patients and examine the influence of lactic acid on immune functions in vitro. Lactic acid suppressed the proliferation and cytokine production of human cytotoxic T lymphocytes (CTLs) up to 95% and led to a 50% decrease in cytotoxic activity. A 24-hour recovery period in lactic acid-free medium restored CTL function. CTLs infiltrating lactic acid-producing multicellular tumor spheroids showed a reduced cytokine production. Pretreatment of tumor spheroids with an inhibitor of lactic acid production prevented this effect. Activated T cells themselves use glycolysis and rely on the efficient secretion of lactic acid, as its intracellular accumulation disturbs their metabolism. Export by monocarboxylate transporter-1 (MCT-1) depends on a gradient between cytoplasmic and extracellular lactic acid concentrations and consequently, blockade of MCT-1 resulted in impaired CTL function. We conclude that high lactic acid concentrations in the tumor environment block lactic acid export in T cells, thereby disturbing their metabolism and function. These findings suggest that targeting this metabolic pathway in tumors is a promising strategy to enhance tumor immunogenicity. 相似文献
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995.
Patty H Spruit Sabine Siesling Marloes AG Elferink Ernest JA Vonk Carel JM Hoekstra 《Radiation oncology (London, England)》2007,2(1):1-6
Background
To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy.Methods
36 patients were studied pre- and post-radiotherapy with18FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters) was correlated with that of maximum standard uptake value (SUV) of the primary lung cancer before and after conventional radiotherapy.Results
There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p < 0.00005). Among the 20 surviving patients, the sensitivity, specificity, and accuracy using PET (SUV) were 94%, 50%, 90% respectively and the corresponding values using and CT (size criteria) were 67%, 50%, and 65% respectively. The metabolic change (SUV) was highly correlated with the change in size by a quadratic function. In addition, the mean percentage metabolic change was significantly larger than that of size change (62.3 ± 32.7% vs 47.1 ± 26.1% respectively, p = 0.03)Conclusion
Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone. 相似文献996.
Pötter R Gnant M Kwasny W Tausch C Handl-Zeller L Pakisch B Taucher S Hammer J Luschin-Ebengreuth G Schmid M Sedlmayer F Stierer M Reiner G Kapp K Hofbauer F Rottenfusser A Pöstlberger S Haider K Draxler W Jakesz R;Austrian Breast Colorectal Cancer Study Group 《International journal of radiation oncology, biology, physics》2007,68(2):334-340
PURPOSE: In women with favorable early breast cancer treated by lumpectomy plus tamoxifen or anastrazole, it remains unclear whether whole breast radiotherapy is beneficial. METHODS AND MATERIAL: Between January 1996 and June 2004, the Austrian Breast and Colorectal Cancer Study Group (ABCSG) randomly assigned 869 women to receive breast radiotherapy +/- boost (n = 414) or not (n = 417) after breast-conserving surgery (ABCSG Study 8A). Favorable early breast cancer was specified as tumor size <3 cm, Grading 1 or 2, negative lymph nodes, positive estrogen and/or progesterone receptor status, and manageable by breast-conserving surgery. Breast radiotherapy was performed after lumpectomy with 2 tangential opposed breast fields with mean 50 Gy, plus boost in 71% of patients with mean 10 Gy, in a median of 6 weeks. The primary endpoint was local relapse-free survival; further endpoints were contralateral breast cancer, distant metastases, and disease-free and overall survival. The median follow-up was 53.8 months. RESULTS: The mean age was 66 years. Overall, there were 21 local relapses, with 2 relapses in the radiotherapy group (5-y rate 0.4%) vs. 19 in the no-radiotherapy group (5.1%), respectively (p = 0.0001, hazard ratio 10.2). Overall relapses occurred in 30 patients, with 7 events in the radiotherapy group (5-y rate 2.1%) vs. 23 events in the no-radiotherapy group (6.1%) (p = 0.002, hazard ratio 3.5). No significant differences were found for distant metastases and overall survival. CONCLUSION: Breast radiotherapy +/- boost in women with favorable early breast cancer after lumpectomy combined with tamoxifen/anastrazole leads to a significant reduction in local and overall relapse. 相似文献
997.
BACKGROUND: The carbohydrate antigen 19-9 (CA 19-9) is currently the most widely used serum tumor marker in pancreatic cancer (PC). CA 19-9 pretreatment levels as well as CA 19-9 kinetics during systemic chemotherapy can provide prognostic information regarding survival of patients with metastatic PC. CASE REPORTS: We report the clinical course of 2 patients with metastatic PC who underwent palliative chemotherapy with gemcitabine. Both patients showed a significant elevation of pretreatment CA 19-9 levels (7,505 and 150,000 U/ml, respectively), however, subsequently they experienced a highly significant reduction (>90%) of CA 19-9 kinetics under gemcitabine chemotherapy. A good disease control and a clinical benefit response were achieved in both patients. Time to tumor progression was 30 weeks and 28 weeks, overall survival 14 months and 11 months, respectively. CONCLUSION: These data indicate that CA 19-9 kinetics under chemotherapy may possibly serve as a useful surrogate marker for time to tumor progression and survival in advanced PC. 相似文献
998.
Rohrmann S Becker N Linseisen J Nieters A Rüdiger T Raaschou-Nielsen O Tjønneland A Johnsen HE Overvad K Kaaks R Bergmann MM Boeing H Benetou V Psaltopoulou T Trichopoulou A Masala G Mattiello A Krogh V Tumino R van Gils CH Peeters PH Bueno-de-Mesquita HB Ros MM Lund E Ardanaz E Chirlaque MD Jakszyn P Larrañaga N Losada A Martínez-García C Agren A Hallmans G Berglund G Manjer J Allen NE Key TJ Bingham S Khaw KT Slimani N Ferrari P Boffetta P Norat T Vineis P Riboli E 《Cancer causes & control : CCC》2007,18(5):537-549
Introduction Lymphomas are a heterogeneous group of malignant diseases of cells of the immune system. The best-established risk factors
are related to dys-regulation of immune function, and evidence suggests that factors such as dietary or lifestyle habits may
be involved in the etiology.
Material and methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), 849 lymphoma cases were identified in a median
follow-up period of 6.4 years. Fruit and vegetable consumption was estimated from validated dietary questionnaires. Cox proportional
hazard models were used to examine the association between fruit and vegetable intake with the risk of lymphomas overall and
subentities.
Results There was no overall association between total fruit and vegetable consumption and risk of lymphoma [hazard ratio (HR) = 0.95,
95% confidence interval (CI) 0.78–1.15 comparing highest with lowest quartile]. However, the risk of diffuse large B-cell
lymphomas (DLBCL) tended to be lower in participants with a high intake of total vegetables (HR = 0.49, 95% CI 0.23–1.02).
Conclusion In this large prospective study, an inverse associations between fruit and vegetable consumption and risk of lymphomas overall
could not be confirmed. Associations with lymphoma subentities such as DLBCL warrant further investigation.
The work described in this article was carried out with the financial support of: Europe Against Cancer Program of the European
Commission (SANCO); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research;
Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia,
Asturia, Basque Country, Murcia and Navarra; the ISCIII Network RCESP (C03/09), Spain; Cancer Research UK; Medical Research
Council, United Kingdom; Stroke Association, United Kingdom; British Heart Foundation; Department of Health, United Kingdom;
Food Standards Agency, United Kingdom; Wellcome Trust, United Kingdom; Greek Ministry of Health; Greek Ministry of Education;
Italian Association for Research on Cancer (AIRC); Italian National Research Council, Fondazione-Istituto Banco Napoli, Italy;
Compagnia di San Paolo; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Swedish Cancer Society;
Swedish Scientific Council; Regional Government of Sk?ne, Sweden; Norwegian Cancer Society; Research Council of Norway; French
League against Cancer (LNCC); National Institute for Health and Medical Research (INSERM), France; Mutuelle Générale de l’Education
Nationale (MGEN), France; 3M Co, France; Gustave Roussy Institute (IGR), France; and General Councils of France. 相似文献
999.
High level of galectin-1 expression is a negative prognostic predictor of recurrence in laryngeal squamous cell carcinomas 总被引:2,自引:0,他引:2
Saussez S Decaestecker C Lorfevre F Cucu DR Mortuaire G Chevalier D Wacreniez A Kaltner H André S Toubeau G Camby I Gabius HJ Kiss R 《International journal of oncology》2007,30(5):1109-1117
Monitoring of gene-expression profiles is assumed to refine tumor characterization of laryngeal squamous cell carcinomas (LSCCs) with a therapeutic perspective. This is especially expected for adhesion/growth-regulatory effectors such as galectins, a class of endogenous lectins. Using computer-assisted microscopy, we investigated the prognostic value contributed by the quantitative determination of the immunohistochemical levels of expression of galectin-1, -3 and -7 in a series of 62 LSCCs including 42 low- and 20 high-stage LSCCs. As galectin-1 may have a key role leading to a tumor escape from immune surveillance, we also investigated whether or not the level of galectin-1 expression correlated with lymphocyte infiltration in LSCCs. The immunohistochemical determination of expression of galectin-1 is of prognostic value in human squamous laryngeal cancers. LSCCs that display high levels of galectin-1 have worse prognoses than laryngeal cancers with low levels of galectin-1 expression. Elevation of galectin-1 levels in laryngeal cancers can contribute to the process of tumor immune escape by killing the activated T-cells and other protumoral activities such as promoting motility or activity of oncogenic H-Ras proteins. The quantitative determination of galectin-1 in LSCCs is an independent prognostic marker when opposed to TNM staging. It has the potential to identify patients unlikely to benefit from T-cell-mediated immunotherapy, although the definitive effector function from its pro- and antitumoral activity profile has not been delineated. 相似文献
1000.