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51.
Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit. 总被引:5,自引:0,他引:5
Hans Herbert Steiner Matteo Mario Bonsanto Philipp Beckhove Michael Brysch Karsten Geletneky Rezvan Ahmadi Rebecca Schuele-Freyer Paul Kremer Golamreza Ranaie Dejana Matejic Harald Bauer Marika Kiessling Stefan Kunze Volker Schirrmacher Christel Herold-Mende 《Journal of clinical oncology》2004,22(21):4272-4281
PURPOSE: Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. PATIENTS AND METHODS: In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. RESULTS: Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P = .024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P < .001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (> or = 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8(+) tumor-infiltrating T-lymphocytes in secondary tumors. CONCLUSION: Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response. 相似文献
52.
Association between the risk for lung adenocarcinoma and a (-4) G-to-A polymorphism in the XPA gene.
Dorota Butkiewicz Odilia Popanda Angela Risch Lutz Edler Hendrik Dienemann Volker Schulz Klaus Kayser Peter Drings Helmut Bartsch Peter Schmezer 《Cancer epidemiology, biomarkers & prevention》2004,13(12):2242-2246
Polymorphisms of genes coding for DNA repair can affect lung cancer risk. A common single nucleotide (-4) G-to-A polymorphism was identified previously in the 5' untranslated region of the XPA gene. In a case-control study in European Caucasians, the influence of this polymorphism on primary lung cancer risk overall and according to histologic subtypes was investigated. Four hundred sixty-three lung cancer cases (including 204 adenocarcinoma and 212 squamous cell carcinoma) and 460 tumor-free hospital controls were investigated using PCR amplification and melting point analysis of sequence-specific hybridization probes. Odds ratios (OR) were calculated by multiple logistic regression analysis adjusting for age, gender, smoking habits, and occupational exposure and showed a slightly enhanced risk for all lung cancer cases as well as for squamous cell carcinoma and adenocarcinoma cases. Gene-environment interactions were analyzed with respect to smoking and occupational exposure. A nearly 3-fold increased risk for adenocarcinoma associated with the XPA AA genotype was observed for occupationally exposed individuals (OR, 2.95; 95% confidence interval, 1.42-6.14) and for heavy smokers (OR, 2.52; 95% confidence interval, 1.17-5.42). No genotype-dependent increase in OR was found for nonexposed individuals or those smoking <20 pack-years. The significant effect of the XPA polymorphism in heavy smokers and occupationally exposed individuals suggests an important gene-environment interaction for the XPA gene. The underlying mechanisms as to why AA homozygotes are predisposed to lung adenocarcinoma and which specific carcinogens are involved remains to be determined. 相似文献
53.
Stacy M Plum Arthur D Hanson Kirk M Volker Hong A Vu B Kim Lee Sim William E Fogler Anne H Fortier 《Clinical cancer research》2003,9(12):4619-4626
PURPOSE: Current combination treatment strategies in malignancy are designed to evaluate the use of cytotoxic drugs and antiangiogenic agents. Endostatin, a fragment of collagen XVIII, specifically inhibits proliferation, migration, and differentiation of endothelial cells in vitro as well as angiogenesis and tumor progression in in vivo models. In this study, we determine the antitumor effect of rhEndostatin administered alone or in combination with Adriamycin against established orthotopic murine mammary carcinoma. EXPERIMENTAL DESIGN: Mice bearing orthotopically established DA-3 mammary adenocarcinoma tumors received varying doses of rhEndostatin alone and in combination with Adriamycin to assess tumor growth inhibition. Additional studies of this in vivo combination included a determination of Adriamycin-induced cardiotoxicity and in vitro effects on human umbilical vein endothelial cell proliferation and cord formation. RESULTS: For single-agent activity, optimal tumor growth inhibition was observed after s.c. administration of 50 mg/kg/day rhEndostatin or 5 mg/kg Adriamycin injected i.v. every 4 days. Combination of Adriamycin with optimal or suboptimal doses of rhEndostatin resulted in synergistic inhibition of DA-3 tumor growth. Importantly, unlike other antiangiogenic agents, rhEndostatin did not exacerbate the cardiotoxicity of Adriamycin. The synergistic interaction between rhEndostatin and Adriamycin was also observed in vitro for inhibition of human umbilical vein endothelial cell proliferation and inhibition of cord formation. CONCLUSIONS: These data suggest that the synergy observed with rhEndostatin in combination with Adriamycin is exerted at the level of the endothelial cell and can result in enhanced tumor growth inhibition. The potential benefit of Adriamycin used in combination with rhEndostatin is being considered for clinical evaluation. 相似文献
54.
Toshifumi Ozaki Silke Flege Matthias Kevric Norbert Lindner Rainer Maas Günter Delling Rudolf Schwarz Arthur R von Hochstetter Mechthild Salzer-Kuntschik Wolfgang E Berdel Heribert Jürgens G Ulrich Exner Peter Reichardt Regine Mayer-Steinacker Volker Ewerbeck Rainer Kotz Winfried Winkelmann Stefan S Bielack 《Journal of clinical oncology》2003,21(2):334-341
PURPOSE: To define patients and tumor characteristics as well as therapy results, patients with pelvic osteosarcoma who were registered in the Cooperative Osteosarcoma Study Group (COSS) were analyzed. PATIENTS AND METHODS: Sixty-seven patients with a high-grade pelvic osteosarcoma were eligible for this analysis. Fifteen patients had primary metastases. All patients received chemotherapy according to COSS protocols. Thirty-eight patients underwent limb-sparing surgery, 12 patients underwent hemipelvectomy, and 17 patients did not undergo definitive surgery. Eleven patients received irradiation to the primary tumor site: four postoperatively and seven as the only form of local therapy. RESULTS: Local failure occurred in 47 of all 67 patients (70%) and in 31 of 50 patients (62%) who underwent definitive surgery. Five-year overall survival (OS) and progression-free survival rates were 27% and 19%, respectively. Large tumor size (P =.0137), primary metastases (P =.0001), and no or intralesional surgery (P <.0001) were poor prognostic factors. In 30 patients with no or intralesional surgery, 11 patients with radiotherapy had better OS than 19 patients without radiotherapy (P =.0033). Among the variables, primary metastasis, large tumor, no or intralesional surgery, no radiotherapy, existence of primary metastasis (relative risk [RR] = 3.456; P =.0009), surgical margin (intralesional or no surgical excision; RR = 5.619; P <.0001), and no radiotherapy (RR = 4.196; P =.0059) were independent poor prognostic factors. CONCLUSION: An operative approach with wide or marginal margins improves local control and OS. If the surgical margin is intralesional or excision is impossible, additional radiotherapy has a positive influence on prognosis. 相似文献
55.
CT-based delineation of lymph node levels and related CTVs in the node-negative neck: DAHANCA, EORTC, GORTEC, NCIC,RTOG consensus guidelines. 总被引:25,自引:0,他引:25
Vincent Grégoire Peter Levendag Kian K Ang Jacques Bernier Marijel Braaksma Volker Budach Cliff Chao Emmanuel Coche Jay S Cooper Guy Cosnard Avraham Eisbruch Samy El-Sayed Bahman Emami Cai Grau Marc Hamoir Nancy Lee Philippe Maingon Karin Muller Hervé Reychler 《Radiotherapy and oncology》2003,69(3):227-236
BACKGROUND AND PURPOSE: The appropriate application of 3-D CRT and IMRT for HNSCC requires a standardization of the procedures for the delineation of the target volumes. Over the past few years, two proposals--the so-called Brussels guidelines from Grégoire et al., and the so-called Rotterdam guidelines from Nowak et al.--emerged from the literature for the delineation of the neck node levels. Detailed examination of these proposals however revealed some important discrepancies. MATERIALS AND METHODS: Within this framework, the Brussels and Rotterdam groups decided to review their guidelines and derive a common set of recommendations for delineation of neck node levels. This proposal was then discussed with representatives of major cooperative groups in Europe (DAHANCA, EORTC, GORTEC) and in North America (NCIC, RTOG), which, after some additional refinements, have endorsed them. The objective of the present article is to present the consensus guidelines for the delineation of the node levels in the node-negative neck. RESULTS AND CONCLUSIONS: First a short discussion of the discrepancies between the previous Brussels and the Rotterdam guidelines is presented. The general philosophy of the consensus guidelines and the methodology used to resolve the various discrepancies are then described. The consensus proposal is then presented and representative CTVs that are consistent with these guidelines are illustrated on CT sections. Last, the limitations of the consensus guidelines are discussed and some concerns about the direct applications of these guidelines to the node-positive neck and the post-operative neck are described. 相似文献
56.
Peter Albers Roswitha Siener Sabine Kliesch Lothar Weissbach Susanne Krege Christoph Sparwasser Harald Schulze Axel Heidenreich Werner de Riese Volker Loy Erhard Bierhoff Christian Wittekind Rolf Fimmers Michael Hartmann 《Journal of clinical oncology》2003,21(8):1505-1512
PURPOSE: To prospectively assess potential risk factors for relapse in clinical stage I nonseminomatous germ cell tumors of the testis (CS I NSGCT). PATIENTS AND METHODS: From September 1996 to May 2002, 200 patients with CS I NSGCT were prospectively assigned to retroperitoneal lymph node dissection (RPLND), and risk factor assessment was performed within a multicenter protocol. One hundred sixty-five patients had an adequate minimum follow-up of 12 months (mean, 34.5 months) or had pathologic stage II. RESULTS: Pathologic stage II disease was found in 27.9% of patients. Only 0.6% of patients relapsed in the retroperitoneum after confirmation of pathologic stage I disease. With reference pathology, vascular invasion (VI) was most predictive of stage in multifactorial analysis (accuracy, 65.1%). However, the positive predictive value (PPV) of VI to predict patients who have metastatic disease or relapse during follow-up was only 52.7%. With absent VI, low-risk patients had a negative predictive value (NPV) of 76.9%. With a combination of several risk factors, the PPV increased to 63.6% and the negative predictive value increased to 86.5%. CONCLUSION: Even with an optimal combination of prognostic factors and reference pathology, more than one third of patients predicted to have pathologic stage II or relapse during follow-up will not harbor metastatic disease and, therefore, would be overtreated with adjuvant therapy. However, patients at low risk may be predicted at an 86.5% level, and thus, surveillance in highly compliant patients would be a valuable option. For high-risk patients, further reduction of adjuvant treatment is necessary. 相似文献
57.
The eicosapentaenoic to docosahexaenoic acid ratio of diets affects the pathogenesis of arthritis in Lew/SSN rats 总被引:6,自引:0,他引:6
Dietary-induced changes in tissue levels of polyunsaturated fatty acids modify inflammatory reactions through changes in the synthesis of lipid and peptide mediators of inflammation. Four semipurified 20% fat diets, based on beef tallow (BT), safflower oil (SFO), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were provided. The DHA and EPA ratios of the (n-3) fatty acid-based diets were 1.1 and 3.4, respectively. The effect of prefeeding diets differing in EPA to DHA ratios prior to the induction of streptococcal cell wall (SCW) arthritis in female Lew/SSN rats was examined. Weanling rats were fed diets for 5 wk before arthritis induction and 5 wk post-arthritis induction. Footpad thickness, hock circumference, plasma and macrophage fatty acids and histological assessment were compared. There were no differences in food intake and final body weights among the groups. Footpad inflammation, reported as percentage change (adjusted for growth) was greatest for rats fed the BT-based diet, intermediate in those fed the SFO-based diet and least for the rats fed the EPA- and DHA-based diets (P < 0.05). Macrophage phospholipids revealed cellular incorporation of EPA and DHA from the fish-oil based diets which modified lipid and peptide mediators of inflammation. Histological sections of rat hocks ranked by severity of arthritis-related changes suggested that the SFO- and EPA-based diets were more successful in ameliorating the destructive arthritic phase in hock joints than the BT- and DHA-based diets (P = 0.09) in this model of arthritis. The course of SCW-induced arthritis can be altered by diet-induced changes in macrophage fatty acid composition. The EPA-based diet is more effective in suppression of inflammation than the DHA-based diet. 相似文献
58.
Juergen Thiele Hans Michael Kvasnicka Robert Fischer Volker Diehl 《Leukemia & lymphoma》1997,24(5):463-481
In this report an attempt has been made to discuss some of the issues pertinent to myelofibrosis complicating chronic myeloproliferative disorders (CMPDs) that are significantly associated with megakaryocyte function. In this context, biochemical, clinical and particularly morphological features were reviewed. Morphological findings based on elaborate techniques were in keeping with the assumption that in chronic myeloid leukemia (1) the number of CD61-positive megakaryocytes, and in particular their precursors were the parameters most closely associated with myelofibrosis (2) an increased content of reticulin fibers in follow-up biopsies significantly correlated with laboratory data indicative of a high tumor burden (anemia, peripheral blasts, hepatosplenomegaly) and thus a more advanced stage of the disease process (3) even a slight increase in reticulin, i.e. doubling of the normal fiber density was associated with a worse prognosis independent of therapeutic regimens given (4) Dynamics of myelofibrosis was significantly influenced by treatment. In this context, calculation of the myelofibrosis progression index (MPI) revealed a higher score following interferon therapy compared with busulfan. In addition, in idiopathic myelofibrosis (5) the evolution of myelofibrosis was unpredictable and according to the MPI, progression occurred at a relatively low rate (6) proliferation and dilatation of sinusoids accompanying intravascular hematopoiesis and collagen type IV deposits were predominant features in later (fibro-osteosclerotic) stages in the course of disease (7) transmural migration of megakaryocytes demonstrated by three dimensional reconstruction revealed a mole-like tunneling through the thickened sinusoidal wall. A very careful assessment of the numerous correlations between bone marrow features and laboratory data will allow clinicians and pathologists to gain a better insight into the mutual relationships between hematological and morphological findings in CMPDs. 相似文献
59.
Bioavailability of long-chain omega-3 polyunsaturated fatty acid enriched luncheon meats 总被引:1,自引:0,他引:1
(Nutr Diet 2005;62:130–137) Objective: To determine the acute and chronic effects of low doses of long chain (LC) n‐3 polyunsaturated fatty acids (PUFA) on plasma LC n‐3 PUFA levels. Design: In the acute study, six healthy omnivores, avoiding fish meals on the day prior to the study, provided a fasting blood sample initially and post prandially at four hours. In the chronic study, 12 healthy subjects provided a fasting blood sample at baseline and three weeks after daily consumption of the test food. Main outcome measures: Plasma non‐esterified fatty acid and phospholipid LC n‐3 PUFA composition. Statistical analysis: Differences in plasma non‐esterified fatty acids and phospholipid LC n‐3 PUFA. A pre‐ and post‐consumption of the test food were assessed using paired t‐tests (spss ). Results: The acute study demonstrated that a low dose of LC n‐3 PUFA (25% eicosapentaenoic acid and 75% docosahexaenoic acid) significantly increased eicosapentaenoic acid levels in plasma of human subjects postprandially from 0.30% to 0.42% of total non‐esterified fatty acids, a per cent change of 39% (P < 0.05). The chronic study demonstrated a significant increase in total n‐3 phospholipids from zero weeks (5.48% of total fatty acids) to three weeks (7.92% of total fatty acids), representing a per cent increase of 44% (P = 0.006). The n‐6 to n‐3 ratio of LC PUFA phospholipids demonstrated a significant reduction from 5.1 at zero weeks to 4.07 at three weeks, representing a reduction of 20% (P = 0.006). Conclusions: These findings demonstrate the bioavailability of LC n‐3 PUFA consumed as a low‐fat omega‐3‐enriched luncheon meat. 相似文献
60.
Sonja Loges Gerhard Heil Melanie Bruweleit Volker Schoder Martin Butzal Uta Fischer Ursula M Gehling Gunter Schuch Dieter K Hossfeld Walter Fiedler 《Journal of clinical oncology》2005,23(6):1109-1117
PURPOSE: Bone marrow neoangiogenesis plays an important pathogenetic and possible prognostic role in acute myeloid leukemia (AML). Members of the vascular endothelial growth factor (VEGF) and angiopoietin family represent the most specific inducers of angiogenesis secreted by AML blasts. We therefore correlated expression of angiogenic factors with clinical variables. PATIENTS AND METHODS: We investigated the expression of VEGF-A, VEGF-C, angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), and the receptor Tie2 by quantitative polymerase chain reaction in a cohort of 90 patients younger than 61 years with de novo AML entered into the German AML Süddeutsche H?moblastose Gruppe Hannover 95 trial. Uni- and multivariate analyses were performed using clinical and gene expression variables. RESULTS: Univariate analysis of overall survival indicated the following variables as prognostic factors: good response on a day-15 bone marrow examination after initiation of induction chemotherapy, karyotype, and high Ang2 expression. In multivariate analysis, only bad response and log Ang2 expression remained of statistical significance, with a hazard ratio of 3.51 (95% CI, 1.91 to 6.47) and 0.75 (95% CI, 0.61 to 0.91), respectively. Subgroup analysis suggested that the prognostic impact of Ang2 expression was especially evident in cohorts with low VEGF-C and Ang1 mRNA levels. CONCLUSION: These results show that expression of Ang2 represents an independent prognostic factor in AML. Additional research into interactions of angiogenic cytokines in the pathogenesis of bone marrow angiogenesis in AML is warranted. 相似文献